Ferroptosis, a novel form of programmed cell death driven by iron-dependent lipid peroxidation, plays a crucial role in both disease treatment and microbial control due to its multi-level regulatory mechanisms. It mainly involves iron metabolism, lipid peroxidation, and antioxidant systems. In the field of disease treatment, ferroptosis is regarded as a highly promising therapeutic target because of its key role in autoimmune diseases, cancer, and cardiovascular diseases. This review systematically summarizes the core regulatory factors of ferroptosis, such as glutathione peroxidase 4 (GPX4) and long-chain acyl-CoA synthetase 4 (ACSL4) and their interaction networks, and deeply explores the application prospects of targeted intervention strategies based on ferroptosis signaling pathways in disease treatment and microbial control. Additionally, we also summarize the current issues faced by ferroptosis in practical applications and proposes strategies, such as nanodelivery, improved drug chemical stability and enhanced water solubility to optimize therapeutic efficacy. We aim to provide a theoretical basis and practical guidelines for exploring more targeted treatments using ferroptosis.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents, and is clinically characterized by inattention, hyperactivity, and impaired impulse control. Despite extensive research, its etiology and pathogenesis remain incompletely understood. The dopamine (DA) deficiency theory constitutes a central framework in current ADHD studies. In-depth investigations of dopamine transporter (DAT) and dopamine receptor (DR) functions have led to the development of mainstream pharmacological treatments, which alleviate symptoms by enhancing DA concentrations and further support the essential role of the dopaminergic system in ADHD. Beyond DA transport and receptor signaling, recent findings suggest that impaired DA release may contribute to DA deficiency. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, composed of synaptosomal-associated protein 25 (SNAP-25), syntaxin-1A (STX1A), and vesicle-associated membrane protein 2 (VAMP2, also known as synaptobrevin 2), serves as the core molecular machinery mediating synaptic vesicle docking and membrane fusion at the presynaptic terminal. As the minimal apparatus driving DA vesicle exocytosis, the SNARE complex precisely regulates presynaptic DA release through coordinated vesicle fusion and recycling. Functional disruptions in SNARE complex assembly, disassembly, or its auxiliary regulatory proteins may hinder effective DA transmission, potentially contributing to DA deficiency and representing a novel molecular mechanism in ADHD pathogenesis. This review summarizes the current understanding of the SNARE complex and its regulatory network, emphasizing their potential roles in the pathogenesis and progression of ADHD, and offering theoretical insights into disease mechanisms and targeted therapeutic strategies.

With the continuous increase in global obesity prevalence, the impact of obesity on reproductive physiology has garnered widespread societal attention. As a metabolic disorder, obesity is typically accompanied by multiple abnormal physiological phenomena, such as excessive adipose accumulation and exacerbated inflammatory responses, which severely compromise the reproductive health of humans and animals. Reproductive damage induced by obesity involves a series of complex biochemical reactions and in vivo metabolic pathways, manifesting as impaired male sperm quality and female fertility. To better understand the relationship between obesity and reproductive physiology, this review summarizes the reproductive injuries caused by obesity and their underlying mechanisms. In the obese state, conditions such as oxidative stress, insulin resistance, and hyperinsulinemia are induced, with adipokines (leptin, adiponectin, resistin, etc.) and inflammatory factors (TNF-α, IL-6, IL-1β, etc.) interacting synergistically to affect the reproductive system. Oxidative stress activates the MAPK and NF-κB pathways, interfering with insulin signaling, while chronic inflammation leads to adipocyte secretory disorders and disrupts the hypothalamic-pituitary-gonadal regulatory axis. Studies have shown that obese males exhibit significantly decreased testosterone levels and impaired sperm quality, whereas obese females suffer from reproductive hormone imbalance, ovulation disorders, and polycystic ovary syndrome. This review discusses how obesity-induced metabolic disorders lead to impaired reproductive physiology in both males and females, along with the underlying mechanisms, providing a theoretical basis for the prevention and treatment of obesity-related reproductive disorders in the future.

Occult hepatitis B virus (HBV) infection (OBI) represents a potential reservoir for HBV transmission, capable of spreading through routes such as blood transfusion. Additionally, OBI can contribute to the chronic progression of hepatitis B-related diseases, sustaining a state of chronic HBV infection. In individuals with compromised immune function or undergoing immunosuppressive therapy, OBI may lead to HBV re-activation, potentially triggering severe liver conditions such as acute hepatitis or liver failure. As a result, OBI poses a significant public health challenge, profoundly impacting the health and well-being of affected populations and complicating HBV infection control efforts in China. Clinically diagnosing OBI remains challenging, but its hallmark is serum hepatitis B surface antigen negative and the presence of HBV covalently closed circular DNA (cccDNA) in the liver. With the increasing focus on achieving functional cure for chronic hepatitis B, both domestic and international guidelines have refined functional cure. Notably, these guidelines acknowledge that cccDNA may persist in the liver tissue of individuals who have achieved functional cure, suggesting resemblance of an occult infection state. Here, we provide a comprehensive overview of OBI, including its definition, classification, public health implications, underlying mechanisms, and clinical reactivation. By updating the understanding of OBI, we aim to raise awareness among clinicians and public health professionals regarding the significance of OBI in the current context and encourage greater attention to this population.

The structure and function of mitochondria and endoplasmic reticulum (ER) are important for maintaining cellular homeostasis. It has been found that the interaction between mitochondria and ER is involved in the occurrence and development of a variety of diseases. The mitochondria-associated ER membrane (MAM) is a membrane contact site between the ER and mitochondria, and is an important communication center between organelles in eukaryotic cell. Calcium channels on the ER side and the mitochondrial side are crucial in the calcium transport process in MAM. The interaction between ER and mitochondria controls mitochondrial biological function and cell survival through calcium transport regulation, and are involved in the occurrence and development of various pathologic process. On the one hand, MAM regulates calcium transport, which is involved in the modulation of various cellular survival and death processes. It plays a profound regulatory role in the damage of tumor cells, neuronal cells, cardiomyocytes, endothelial cells and nucleus pulposus cells through different key molecules within MAM.On the other hand, the regulation of MAM in calcium transport is crucial in the development of mitochondrial dysfunction in Hepa 1-6 cells, the synthesis and secretion of pancreatic β-cells and amyotrophic lateral sclerosis. In addition, MAM also affects cellular transcription processes by regulating calcium transport, thereby exerting significant regulatory effects on angiogenesis and breast cancer. This paper reviews the structural features and pathophysiologic role of calcium transport regulation of MAM, and expects to provide new horizons for prevention and treatment of related diseases targeting MAM.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social interaction, communication, and repetitive behaviors. Accumulating evidence suggests that neuroimmune inflammatory responses may contribute to the pathogenesis of ASD. Within the central nervous system, microglia, as the key innate immune cells, play a pivotal role in shaping the neuroimmune inflammatory microenvironment. This review systematically synthesizes findings regarding alterations in microglial number and morphology across two major categories of ASD mouse models, considering both genetic and environmental dimensions. Specifically, it examines changes in dendritic spine density and neurotransmission function in gene mutation-induced models and environmentally triggered models, such as maternal immune activation models. Furthermore, this article highlights comparative analyses of shared mechanisms, including the interleukin-17 receptor A signaling pathway and the mammalian target of rapamycin signaling pathway, between MIA models and genetically induced BTBR T⁺Itpr3^tf/J mouse models. Building on these insights, the review elaborates on cytokine dysregulation in abnormally activated microglia, mitochondrial oxidative phosphorylation dysfunction, and elevated reactive oxygen species levels within ASD mouse brains, elucidating their implications for cellular function. Finally, the article summarizes how microglia influence neurodevelopment through neurogenesis and synaptic formation and function, exploring potential pathways underlying autism-like behavioral phenotypes and identifying novel therapeutic targets for clinical ASD intervention.

Monkeypox is a viral zoonotic disease, and there is currently a lack of safe and effective vaccines against the monkeypox virus. Therefore, screening and developing vaccine candidates is of significant practical importance. With the rapid advancement of molecular biology and plant genetic engineering, plant bioreactors offer promising potential for producing vaccine proteins due to their advantages, including safety, cost-effectiveness, and scalability. In this study, we focused on the monkeypox protein B6R. The recombinant expression plasmid pFolia40108-B6R-Fer was successfully constructed using amplification, enzyme digestion, and flexible linker tandem ferritin technology. A complete transient expression system in Nicotiana benthamiana and a purification system for the recombinant monkeypox protein were established. The optimal expression time was determined to be 12-14 days, with a final purified protein concentration of approximately 1 mg/mL and a yield of 0.85 mg/kg fresh weight. The purified B6R-Fer recombinant protein self-assembled into spherical virus-like particles (VLPs) with an average particle size of 24 nm. The B6R-Fer recombinant protein from this study shows promising potential for use in the development and screening of plant-derived monkeypox vaccine candidates.

Every year, up to 800 million tons of hydrocarbons enter the environment globally, most of which are alkanes. Due to the inactive property and the high freezing points, alkanes have caused serious problems on environmental ecology and oil recovery. Alkane monooxygenase (AlkB) is a transmembrane metalloproteinase, and belongs to the membrane-bound fatty acid desaturase (FADS) family, which is able to convert straight-chain alkanes into the corresponding primary alcohols during the first step of alkane degradation mediated by microorganisms. Thus, AlkB plays a crucial role in the global carbon cycle and bioremediation of oil pollution. In this paper, the characteristics, structure, active site, catalytic mechanism, and the construction of recombinant bacteria of AlkB from different microorganisms were reviewed. In addition, the important significance of AlkB for environmental remediation and oil extraction was also emphasized, which would provide new clues for the bioremediation of hydrocarbon-contaminated sites and improvement of oil recovery rate by AlkB.

The MYB protein family is one of the largest transcription factor families in plants, widely involved in growth and development, stress responses, and secondary metabolism. However, the MYB protein family members in Lonicera japonica have not been identified yet. In this study, a genome-wide identification and analysis of the MYB protein family in L. japonica was conducted using bioinformatics methods, covering basic physicochemical properties, phylogenetic trees, gene structures, conserved motifs, and cis-acting elements. Additionally, the subcellular localization of MYB6, MYB106d, and MYB114 proteins was detected through the construction of pCAMBIA1300-GFP fusion vectors and transient transformation in Nicotiana benthamiana leaves. The results showed that a total of 147 LjMYB genes were identified, belonging to 17 subfamilies (S1-S17). The encoded amino acid lengths ranged from 52 to 1 060 AA, isoelectric points from 4.42 to 11.52 pI, and the number of exons from 1 to 13, with molecular weights ranging from 6 086.3 to 119 075.08 kD. MEME analysis revealed that the number and distribution of motifs in different MYB proteins varied, while the structural features within the same subfamily were similar. The analysis of cis-acting elements indicated that the promoter regions contained light-responsive, hormone-responsive, and biotic and abiotic stress-related elements and binding sites. Chromosome distribution showed significant genome doubling of MYB genes (possibly related to chromosome evolution doubling). The collinearity analysis of MYB genes between L. japonica and Arabidopsis thaliana revealed 121 pairs of homologous genes distributed across all A. thaliana chromosomes, demonstrating evolutionary conservation. Expression profile analysis indicated that L. japonica MYB genes played different roles in growth and development and had varying sensitivities to different light intensities. Subcellular localization showed that LjMYB6, LjMYB106d, and LjMYB114 were all localized in the nucleus. In conclusion, the MYB protein family in L. japonica has diverse biological characteristics and may be involved in growth and development, hormone regulation, and biotic and abiotic stress responses.

Most recently, Quake proposed the “cellular dogma” in which the central dogma, cell theory and theory of evolution should be integrated to understand a major conceptual challenge for biology in the next decade. However, the “cellular dogma” remains to be developed theoretically and experimentally. Quantum biology is an interdisciplinary field to study quantum effects in dynamic structures of biological molecules and energy transfer, and further understand the quantum mechanics of chemical processes and the origin of life by using quantum theories and methods. We wonder whether quantum biology could explain the basic nature of life in the most general sense. Herein, we first provide a brief review on the development of quantum mechanics and the conceptions in quantum biology, then we summarize the present theories of quantum biology and discuss a possible prospectives. We cover the following contents of quantum biology: Quantum tunneling due to a decrease of proton stability by hydrogen bond breakage in DNA replication and repair cause permanent mutations with evolutionary impacts; the tunneling due to conformational short-range motion and static environment optimization in enzyme molecules is found to promote enzymatic reactions by reduction of the effective barrier height; the activated electrons are in a phase-synchronized superposition state between multiple pigment molecules, enhancing the conversion of light energy into chemical energy with high efficiency by optimizing the energy transfer path through phase-length interference; quantum compasses in bird migration lead to sense the way by detecting weak magnetic fields through electron transfer and successive conformational changes in cryptochrome; collapses of conformational state of microtubules in the nervous system due to quantum coherence, superposition, entanglement and Orchestrated Objective Reduction (Orch-OR) collapse can sense and transmit neuro-information. Finally, the paper also discusses the possibilities and prospectives in experimental evidence for quantum mechanical simulation of life activities, whether the “observer effect” may provide new ideas for explaining the origin of life, and whether the Copenhagen interpretation could explain the basic nature of life.

In order to investigate the teaching effectiveness of artificial intelligence (AI) in molecular biology, this study selected students from the Animal Medicine major of the College of Animal Science and Technology at Hebei North University in 2022 and 2023 as research subjects. There was no significant difference in professional foundation, admission scores, and other aspects between the two grades, and they were taught by the same lecturer to ensure the reliability of research results. The 2022 students will adopt the traditional teaching mode, while the 2023 students will implement the AI-enabled teaching mode, which includes four stages: pre class exploration, in class assistance, post class learning support, and teaching reflection and improvement. Before class, the teaching team pushes teaching videos of various knowledge points in the course and relevant preview materials organized by the AI system to students to complete self-learning, and use AI systems to track students' learning difficulties. In class, the teacher uses various teaching methods such as case teaching, group discussions, AI animation demonstrations and virtual experiments, etc.. Thus, they provide in-depth explanations of key contents based on the feedback data from the intelligent learning companion AI system, promoting students' understanding of the knowledge. After class, the AI system generates personalized learning plans for students and provides different levels of learning resources to broaden their horizons. At the same time, the AI system provides teachers with students' learning data analysis reports, and teachers can adjust and optimize their teaching plans accordingly. Research has found that students in the 2023 AI-empowered teaching class have significantly higher satisfaction in multiple dimensions such as learning interest, understanding and mastery of knowledge points, and cultivation of scientific research thinking than those in the 2022 traditional teaching class. In terms of student participation in comprehensive activities, the proportion of 2023 students participating in subject competitions and innovation and entrepreneurship activities has significantly increased. In terms of academic performance, the mid-term, laboratory, and final grades of 2023 students are higher than those of 2022 students, with a significant increase in the excellence rate and a significant decrease in the failure rate. The results indicate that the application of AI technology in molecular biology teaching has stimulated students' interest in learning, helped them better understand and master knowledge, significantly improved their academic performance. In sum, it has a positive impact on improving teaching quality.

Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells within the bone marrow, with pathological features including abnormal secretion of monoclonal immunoglobulins, osteolytic bone disease, and multi-organ dysfunction. Despite significant advancements in therapeutic approaches that have markedly extended patient survival, primary drug resistance and relapse remain major obstacles to clinical cure. The pathogenesis and progression of MM are intricately regulated by the bone marrow microenvironment (BMME), a dynamic network composed of diverse cellular and non-cellular components. The BMME not only supports the survival and proliferation of MM cells but also plays a pivotal role in disease progression by modulating bone metabolic homeostasis, mediating immune escape, and promoting drug resistance. In recent years, groundbreaking therapeutic strategies targeting the BMME have emerged, including immunomodulatory drugs, bispecific antibodies, CAR T-cell therapies, and microenvironment-modulating agents. These approaches have significantly improved objective response rates and survival outcomes in relapsed/refractory MM by disrupting cytokine signaling, reprogramming the immunosuppressive microenvironment, or inhibiting tumor-stromal interactions. However, challenges such as drug resistance, treatment-related toxicity, and tumor heterogeneity persist in clinical practice. This review systematically delineates the roles of BMME components in MM pathogenesis, analyzes the molecular mechanisms underlying MM cell-BMME interactions, and explores innovative strategies to enhance therapeutic efficacy and prognosis through targeted modulation of the BMME. These insights provide a foundation for developing novel therapeutic paradigms aimed at overcoming current limitations in MM treatment.

Biotoxins are widely distributed in animals, plants, and microorganisms, functioning as “chemical weapons” of proteins, peptides, or small molecules that evolved for predation, defense, and competition. Compared with general chemical toxins, biotoxins exhibit high potency, strong specificity, and remarkable molecular diversity. While posing potential threats to human health, they also provide unique value in elucidating disease mechanisms and inspiring drug development. Representative drugs such as captopril, botulinum toxin, ziconotide, and GLP-1 receptor agonists mark milestones in the therapeutic application of toxins. To date, over one hundred biotoxin-derived drug candidates have entered clinical trials across multiple major diseases. However, this field still faces challenges, including low efficiency in resource discovery, limited structural and mechanistic insights, inherent toxicity, and constraints in synthesis and modification technologies. Looking forward, advances in multi-omics, artificial intelligence, and synthetic biology will drive efficient toxin discovery, detoxification strategies, and precision applications, ultimately promoting a closed-loop progression from basic research to clinical translation.

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, as a crucial component of innate immunity, plays a pivotal role in anti-tumor immunity. cGAS recognizes aberrant endogenous or exogenous DNA and catalyzes the synthesis of the second messenger cGAMP, which activates the STING protein. This triggers the TBK1-IRF3/NF-κB signaling axis to induce the secretion of cytokines such as interferon-I and other cytokines, which activates dendritic cells, enhances natural killer cell function, promotes T cell responses, and strengthens immune surveillance, thereby inhibiting tumor progression. However, tumor cells can perform immune surveillance via multiple mechanisms, including downregulation of cGAS/STING expression, accelerated STING protein degradation, or inhibition of cGAMP synthesis and signal transduction, leading to the formation of an immunosuppressive microenvironment and facilitating tumor immune escape. Current strategies to target cGAS-STING pathway activation primarily involve the development of STING agonists, optimization of delivery systems, and combination therapies with PD-1/PD-L1 inhibitors, radiotherapy, or chemotherapy to synergistically enhance antitumor immune responses. Despite promising prospects, this field still faces challenges such as systemic toxicity of STING agonists, tumor microenvironment heterogeneity, and drug resistance mechanisms. This review summarizes the function and molecular mechanisms of the cGAS-STING pathway, its role in tumor immunity, the development in STING agonists and delivery systems, as well as its potential for combination with immune checkpoint inhibitors, radiotherapy, and chemotherapy. It also discusses the challenges and optimization directions for targeting the cGAS-STING pathway, providing theoretical foundations and insights for developing more effective tumor immunotherapy strategies.

Orphan G protein-coupled receptor 35 (GPR35) is a GPCR that modulates lipid metabolism and exerts cell-type-specific metabolic control in distinct adipocyte populations. In white adipocytes, GPR35 regulates both lipolysis and lipogenesis, and is tightly linked to insulin sensitivity and inflammatory responses. In brown adipocytes, it orchestrates lineage commitment and energy expenditure by activating uncoupling protein 1 (UCP1) and regulator of G-protein signaling 14 (RGS14). In beige adipocytes, GPR35 promotes “browning”, fine-tunes mitochondrial function, and governs thermogenic capacity. Within adipose tissue, GPR35 further modulates immune, neuronal, and vascular compartments—alleviating inflammation and tuning blood flow—to orchestrate intercellular crosstalk that ultimately shapes adipocyte metabolism. Clinical studies of obesity, type 2 diabetes, and MASLD have implicated GPR35 in lipolysis, energy expenditure, insulin sensitivity, and inflammatory tone. Nevertheless, its precise mechanisms remain incompletely understood, and the selectivity of candidate ligands requires optimization, leaving therapeutic translation still fraught with challenges. Future work should leverage molecular docking, deep-learning models, and genome-editing technologies to clarify GPR35 function, validate drug specificity, and develop innovative therapeutic strategies for metabolic diseases.

tRNA is one of the RNA molecules with the most diverse post-transcriptional modifications. It not only functions as an adaptor molecule transporting amino acids during translation but also relies on its extensive post-transcriptional modifications to regulate gene expression, thereby influencing numerous biological processes. These modifications are dynamically regulated by tRNA methyltransferases and demethylases, which collaboratively maintain a balance—the former catalyze methyl group addition, while the latter remove methyl groups, ensuring reversible control. Mutations or dysregulation of these enzymes are closely associated with tumorigenesis and other diseases, constituting a major research focus. They promote tumor progression through two distinct pathways: cytoplasmic tRNA (ctRNA) methylation enhances the translation of oncogenes, whereas mitochondrial tRNA (mtRNA) methylation optimizes mitochondrial protein synthesis to reprogram energy metabolism. From the dual dimensions of"enzyme supply" and"energy provision", tRNA methylation establishes a material foundation for tumor cell growth and directly contributes to cell cycle dysregulation. The cell cycle, an orderly process governing cell division, is tightly controlled by checkpoint proteins to guarantee accurate genetic information transmission. Notably, aberrant cell cycle activation is not only a hallmark of cancer but also a pivotal therapeutic target. tRNA methyltransferases and demethylases exert multidimensional control over both cell cycle progression and metabolic adaptation. Elucidating the mechanisms underlying tRNA modification mediated cell cycle regulation will not only accelerate the discovery of novel therapeutic targets but may also overcome the constraints of conventional cell cycle targeted therapies. Within this context, we systematically review the molecular mechanisms by which tRNA methylation-modifying enzymes regulate the cell cycle, with an emphasis on their translational potential.

O-glycosylation (including mucin-type O-glycosylation and O-GlcNAcylation), as a critical post-translational modification (PTM), regulates protein function, stability, and subcellular localization through the addition of glycan chains to serine or threonine residues, which participates in cellular signaling, metabolic regulation, and stress responses. DNA damage refers to the disruption of genomic integrity caused by endogenous factors (e.g., metabolic byproducts, replication errors) or exogenous agents (e.g., radiation, chemical substances), leading to carcinogenesis, aging, and genetic disorders. To counteract DNA lesions, organisms have evolved the DNA damage response (DDR) system, which orchestrates complex protein networks to detect DNA damage and facilitate repair processes. Emerging evidence indicates that O-glycosylation can modulate DDR by influencing the activity, localization, and interactions of DNA repair-associated proteins. However, the precise mechanisms underlying O-glycosylation-mediated DDR remain to be clarified. This review systematically summarizes: (1) the biosynthetic pathways of mucin-type O-glycosylation and O-GlcNAcylation, the cascade reactions in DDR; and (2) current research advances regarding O-glycosylation in tumor-associated DDR. Furthermore, we propose novel mechanistic perspectives and therapeutic strategies targeting O-glycosylation-mediated DDR dysregulation in malignancies, aiming to provide a theoretical basis for tumor treatment.

Multiple myeloma (MM) is a hematologic malignancy originating from plasma cells in the bone marrow. In recent years, the use of novel drugs and hematopoietic stem cell transplantation (HSCT) has significantly improved the prognosis of MM patients. However, MM remains challenging to cure and is prone to relapse and resistance. For patients with relapsed/refractory multiple myeloma (RRMM), there is an urgent need to explore novel therapeutic approaches. Bispecific antibodies (BsAbs) are a promising class of immunotherapeutics that functions by simultaneously binding to tumor cell antigens and endogenous effector cells, thereby forming an immunological synapse. This interaction facilitates the activation of effector cells, leading to the targeted lysis of tumor cells. Numerous clinical studies have demonstrated the significant efficacy of BsAbs, either as monotherapy or in combination with other treatment regimens, in patients with RRMM. This article summarizes the mechanisms of action, efficacy, and safety of BsAbs, and discusses optimal sequencing strategies in immunotherapy, aiming to provide new perspectives for the treatment of MM.

This study aims to explore the efficacy and mechanisms of achyranthes bidentata extract on chondrocytes pyroptosis and cartilage injury in knee asteoarthritis in a rat model. A rat KOA model was constructed using “medial collateral ligament transection (MCLT) + partial meniscectomy (PM)”method. Hematoxylin and eosin (H&E) staining and safranin O/fast green staining were performed to estimate the pathological status of the damage. TUNEL staining was performed to detect the chondrocytes pyroptosis. Micro-CT was used to assess bone damage and KOA severity. LPS-treated chondrocytes extracted from rat knee cartilage were used as an in vitro model. Cytotoxicity and cell viability were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) kit. The levels of inflammatory cytokine and stromal proteins were quantified by ELISA and Western blot assays. Caspase-1 activity was evaluated by flow cytometry. The level of NLRP3 in chondrocytes was examined by immunofluorescence. Our results revealed that ABE inhibits rat chondrocyte injury and pyroptosis by reducing the levels of LDH (P<0.01), IL-18 (P<0.01), IL-1β (P<0.01), MMP-1 (P<0.01), and MMP-13 (P<0.001) at the same time increasing collagen II (P<0.001) expression. Furthermore, ABE suppressed the NLRP3 (P<0.001) inflammasome and Caspase-1 (P<0.001) signaling pathways to alleviate pyroptosis. The inhibitory effects of ABE on chondrocyte pyroptosis were mediated by P2X7R regulation. P2X7R overexpression suppressed the above positive changes caused by ABE. We further confirmed that ABE could prevent the pathological conditions in the rat KOA model by suppressing P2X7R/NLRP3-mediated pyroptosis. In conclusions, ABE suppressed KOA progress by repressing P2X7R/NLRP3 signaling-mediated pyroptosis in chondrocytes and rat KOA models, indicating that ABE may act as a promising medicine for KOA treatment.

The origin of life and its organizing principlesrepresent a long-standing hard problem in science. Because information, together with matter and energy, form the three cornerstones of our knowledge system and perhaps even the universe, we ask whether life can be defined from a purely mathematical and information science perspective. Here, we postulate a unified mathematic framework termed the Self-Information Theory of Life to define what life is and how it operates. Our theory states that all dynamic activity events in life—including DNA replication, RNA transcription, protein synthesis, cellular signaling, energy metabolism and even the brain’s high cognition—carry the hidden and intrinsic self-information based on their probability distributions using the ternary coding scheme. Specifically, the events with a higher probability distribution carry lower information content, whereas those lower probability events carry higher information content. The high-probability events represent the ground equilibrium state, whereas those low-probability states that deviate from this ground state signal positive surprisal or negative surprisal information, depending on the direction of the deviation. Thus, a given biochemical or biophysical step can be regarded as a self-information unit which generates the dynamic ternary information code explicitly tagged with a specific self-information value. A living organism is constructed by a set of self-information units organized in such a way to further produce their joint self-information probability distribution as the joint self-information groups. Through the feedback control mechanisms, these joint self-information groups form various closed loops to process both environmental inputs, to maintain internal homeostasis and to generate adaptive outputs, subsequently generating the chain of joint self-information flow. Those spatiotemporally ordered activities of each joint self-information group execute a specific given function such as gene replication, protein synthesis, energy metabolism, intracellular and neuronal signaling, learning and memory, intelligent and conscious behaviors, etc. The more advanced a life evolves (i.e. human), the larger numbers of the self-information units and joint self-information groups are, the richer self-information conscious levels and higher intelligence, thereby the lower its life entropy value is. Life and its activity defined by this purely mathematical and self-information principle surpass the traditional realm of matter and energy. This self-information theory of life may further provide a novel framework to design and build artificial life on earth or to explore and study extraterrestrial life in the Universe.

Rhabdomyosarcoma (RMS) is one of the most common malignant soft-tissue tumors in children and adolescents, characterized by a blockade of skeletal-muscle differentiation. Here we summarize basic studies and key advances in the field. We cover three aspects in RMS: differentiation control, cell-cycle regulation, and signaling networks. During early differentiation, Myogenic Differentiation 1 (MyoD) heterodimerizes with E-proteins and initiates muscle-lineage gene programs together with muscle-specific miR-206 and selected lncRNAs. During late differentiation, Myogenin orchestrates myoblast fusion and myotube maturation, while its activity and stability are modulated by upstream regulators including the miR-1-TRPS1 axis, Arp5, and IL-4/STAT6. At the cell-cycle level, the p21/p27 and Rb-E2F axes promote G₁ arrest to license differentiation. When these signaling pathways are disrupted, tumor cells maintain high proliferative activity, but cell differentiation is blocked. At the signaling level, aberrant activation of PI3K/AKT/mTOR and MAPK/ERK, together with differentiation-suppressive pathways such as Notch and Hedgehog, interconnect to form a self-sustaining “proliferation-de-differentiation” loop. Mechanistically informed strategies—including inhibition of aberrant pathways, correction of epigenetic and non-coding RNA imbalances, restoration of MyoD/Myogenin function, and CRISPR-based precision interventions—show potential to induce differentiation and restrain tumor progression. Remaining challenges include unclear causal relationships among pathways and subtype-specific drivers, a paucity of predictive biomarkers, and insufficient definition of therapeutic windows and resistance dynamics for combination regimens. Future work should leverage single-cell and spatial omics to integrate epigenetic and post-transcriptional layers, reconstruct actionable differentiation networks, and—under biomarker guidance—develop and stratify cross-pathway combination strategies to advance RMS differentiation therapy toward precision and clinical translation.

Lactylation modification is a new type of protein post-translational modification, which mediates the covalent binding of lactic acid groups to lysine residues through amide bonds, thus changing protein function and intracellular signal transduction process. Lactylation modifications can be broadly categorized into two types: histone lactylation and non-histone lactylation, both of which are dynamically and precisely regulated by the "Writer-Eraser" enzyme system. Among them, non-histone lactylation, mainly regulated by enzymes such as AARS1 and SIRT3, plays an important role in the progression of many diseases, including tumor metabolic reprogramming, ROS stress and signal pathway regulation. Especially in tumors, non-histone lactylation is closely related to tumor proliferation, immune escape and drug resistance. Therefore, an in-depth study of the role of non-histone lactylation in the progression of tumors is expected to provide new targets and strategies for the accurate diagnosis and treatment of tumors. It is noteworthy that in the context of non-histone lactylation modification, the interference effect of acetylation modification cannot be ignored. Lactylation and acetylation share similar "writer" and "eraser" enzymes and exhibit overlapping modification sites, suggesting the possibility of functional crosstalk between the two. Due to the current lack of specific editing tools targeting lysine lactylation, it remains challenging to definitively determine whether lactylation plays a predominant regulatory role. This article reviews the research progress of non-histone lactylation in tumors in recent years.

Set against the artificial intelligence (AI)-driven transformation of the educational landscape, this paper discusses how the Molecular Biology course is implementing a question-driven pedagogical reform, centering on fostering innovation as its primary goal. We introduce the educational philosophy of “Co-evolution of Inquiry and Learning”, positing that questioning and knowledge acquisition function as interdependent strands—analogous to DNA’s double helix—mutually catalyzing cognitive development and igniting innovative potential. Guided by this conceptual framework, a comprehensive instructional system has been constructed. At the content level, a three-level question bank (Foundational Cognition-Comprehensive Application-Innovative Exploration) incorporates AI tools to streamline knowledge acquisition, enhance complex problem-solving capabilities,and facilitate cutting-edge research exploration. Methodologically, the four-step teaching method (ContextualQuestioning-Autonomous Inquiry-Collaborative Discussion-Reflective Questioning) systematically activates the question bank through sequenced implementation, enabling students’transition from responding to instructor-initiated questions to generating original inquiries. The formative assessment system examines five dimensions of students’competencies while providing timely diagnostic feedback. Through two years of implementation, this AI-enhanced “inquiry-initiated, mutually reinforcing” pedagogical model has successfully transformed Molecular Biology course instruction from knowledge transmission to cognitive cultivation, demonstrating significant improvements in students’scientific reasoning, self-regulated learning capacities, and innovative practical abilities. This teaching innovation offers a forward-looking and implementable pathway for reforming core STEM curricula in the modern era.

Breast cancer (BRCA) remains one of the leading causes of cancer-related deaths worldwide due to its high rates of metastasis and recurrence, making it crucial to explore its underlying molecular mechanisms. Our previous study demonstrated that miR-326 inhibits BRCA progression by targetingEPH receptor B3(EPHB3). This study further explores the molecular mechanism by which long non-coding RNAs (LncRNAs) regulates BRCA progression via the competing endogenous RNA (ceRNA) mechanism, in which it competes with EPHB3 for miR-326 binding. Bioinformatics analysis identified LncRNA Small Nucleolar RNA Host Gene 12 (SNHG12) as a potential miR-326-binding molecule. SNHG12 was found to be significantly upregulated in BRCA tissues, exhibiting a negative correlation trend with miR-326 and a positive correlation trend with EPHB3, suggesting its potential involvement in the ceRNA regulatory network. Nuclear-cytoplasmic fractionation assays revealed cytoplasmic localization of SNHG12, while dual-luciferase reporter assays confirmed its direct binding to miR-326. Functional experiments demonstrated that SNHG12 knockdown significantly suppressed BRCA cell proliferation, invasion, and migration, while miR-326 inhibition reversed these effects. Furthermore, miRNA pulldown assay revealed significant enrichment of SNHG12 and EPHB3 in the miR-326 pulldown products, indicating direct binding between them. Western blotting and rescue experiments revealed that SNHG12 upregulates EPHB3 expression by sponging miR-326, thereby promoting the malignant behaviors of BRCA cells. Collectively, this study revealed that LncRNA SNHG12 promotes BRCA progression by regulating the miR-326/EPHB3 axis through a ceRNA mechanism. The SNHG12/miR-326/EPHB3 pathway may represent a promising target for the molecular diagnosis and targeted therapy of BRCA.

Wound healing is a dynamic physiological process involving haemostasis, inflammation, proliferation and tissue remodeling. Skin injuries, such as diabetic foot ulcers, venous ulcers, and pressure ulcers, are difficult to heal and impose a serious physical and psychological burden on patients, and traditional treatments are difficult to address such problems. In recent years, Chinese herbal medicine-derived extracellular vesicles (CHMEVs) have shown promising potential in the field of wound repair and drug delivery due to their excellent biocompatibility, low immunogenicity and high safety. CHMEVs are nano-like particles enriched with herbal small molecule compounds, proteins and metabolites, and are able to cross biological barriers and effectively regulate intercellular communication to promote tissue repair. In this review, the isolation and extraction methods of CHMEVs and their roles in wound repair are reviewed, and the prospects and challenges of their clinical applications are discussed. The combination of engineered modification and biomaterials of CHMEVs further expands their potential for application in precision medicine and provides a new idea for the treatment of hard-to-heal wounds in the future.

Atherosclerosis (AS) is a vascular disease characterized by lipid deposition, chronic inflammation, and plaque formation, serving as the primary pathological basis for cardiovascular events. Although conventional lipid-lowering therapies have achieved certain clinical efficacy, the underlying core pathogenesis remains to be further elucidated. In recent years, the gut-brain axis, a bidirectional regulatory network connecting the gastrointestinal tract and central nervous system, has gradually become a research hotspot in AS due to its pivotal role in the interaction between neuroendocrine immunity and metabolism. The gut-brain axis influences AS progression through the gut microbiota-derived metabolites such as short chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO) and intestinal hormones, which modulate host inflammation, lipid metabolism, and endothelial function; the autonomic nervous system (sympathetic/parasympathetic) affects plaque stability by regulating immune cell activity and inflammatory cytokine release. Dysregulated neuro-metabolic crosstalk may exacerbate microbial imbalance and metabolic disturbances, promoting a vicious cycle of AS progression. This review systematically summarizes the complex bidirectional signaling mechanisms between gut microbiota and the host nervous system, as well as their roles in the pathogenesis and progression of AS. It explores how gut microbiota regulate the host’s neuroendocrine and immune responses through metabolic products, thereby influencing the function of both the central and peripheral nervous systems; conversely, neural activities can also directly or indirectly modulate the homeostasis of the gut microbiota. Finally, the paper further outlines interventional strategies targeting the gut-brain axis for the treatment of AS and discusses their clinical feasibility. These findings provide theoretical foundations for developing precision prevention and treatment strategies centered on gut-brain axis regulation, while also identifying promising new targets and research directions for clinical interventions.

Methcathinone, a widely abused synthetic cathinone, poses a significant public health risk because of its severe neurotoxicity and high addictive potential. In this study, we used a zebrafish model to investigate the mechanisms underlying its neurobehavioural effects. Methcathinone exposure reduced larval survival and induced a range of abnormal behaviours. Most notably, conditioned place preference (CPP) tests demonstrated the potent rewarding properties of methcathinone, as shown by a significant 22.2% increase in time spent in the drug-paired light zone compared with baseline(P<0.01). Transcriptomic analysis of brain tissue revealed systemic disruption of the neuroactive ligand-receptor interaction pathway. Gene set enrichment analysis (GSEA) further revealed significant suppression of γ-aminobutyric acid (GABA) signalling (NES =-1.64, P<0.05) and glutamate receptor signalling, including ionotropic and AMPA receptor signalling (P<0.05). Quantitative PCR validation confirmed the marked downregulation of key genes involved in these pathways: the mRNA expression of GABAergic receptors(e.g., gabra1 and gabra2), glutamatergic receptors (e.g., gria2 and grin2B), and the dopamine transporter slc6a3 decreased by 67.0% to 97.9% (all P <0.01). These results suggest that methcathinone drives reward-seeking behaviour through a synergistic dual-target mechanism; specifically, the concurrent suppression of GABAergic inhibition and slc6a3-mediated reuptake likely facilitates dopaminergic hyperactivity, whereas the downregulation of glutamate receptors reflects a homeostatic response to overstimulation. Our findings provide novel mechanistic insight into the development of methcathinone use disorder in humans.

The development of tailor-made tumor vaccines targeting specific tumor antigens is crucial for improving treatment accuracy. Tumor mRNA, as an emerging and promising vaccine modality, holds distinct technical edge in addressing this challenge, thus attracting considerable attention in cancer treatment. This article reviews the design and synthesis processes of tumor mRNA vaccines, highlighting the latest advances in antigen identification, optimization of RNA sequence and structure, and its delivery. Additionally, it discusses the challenges these vaccines face and outlines potential future directions for development.

Lung cancer poses a serious threat to global public health security. Chemotherapy, as the main strategy for cancer treatment, faces challenges such as high toxicity and drug resistance. Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity, rapid action, and difficulty in generating drug resistance, but they also face shortcomings such as weak activity and strong toxic side effects. The weakly acidic microenvironment of tumors (pH 6.5-6.8) provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity. Previously, we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider (Lycosa singoriensis) toxin Lycosin-I as a template. In this study, we found that pHly-1 also had acid-sensitive anticancer activity. Further alanine scanning analysis of pHly-1 was carried out, and we obtained a mutant pHTP-2 with better acid sensitivity, whose IC₅₀ (half maximal inhibitory concentration) against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4. At pH 6.6, pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid lysis; at pH 7.4, 500 μmol/L pHTP-2 had weak toxicity to red blood cells (the hemolysis rate was approximately 38%) and primary myocardial cells (the inhibition rate was 49.7%, with P< 0.05). Analysis of its charge, particle size, morphology, and secondary structure showed that at pH 6.6, the histidine in the sequence of pHTP-2 was protonated, increasing the positive charge (P<0.01), decreasing the hydrated particle size (P<0.05) and forming an α-helical structure to induce membrane lysis of A549 cells. At pH 7.4, it was deprotonated, the positive charge decreases, a β-sheet structure was formed and self-aggregation occurred, limiting its effect on the A549 cell membrane and showing weak activity. In summary, pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cytotoxic activity, effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity. Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Mitochondria are the energy centers of cells, and their gene expression regulation is essential for maintaining cellular homeostasis. The mitochondrial genome is a circular double-stranded DNA molecule, and its transcription depends on a transcriptional machinery composed of multiple nuclear-encoded proteins. During transcription initiation, POLRMT uses NAD as a non-canonical initiation nucleotide at the start of transcription, forming a 5′NAD cap, which links transcription with the cell′s metabolic state. The mitochondrial DNA is transcribed into long, continuous polycistronic precursor transcripts, which require subsequent processing and modification to become mature. These steps take place in mitochondrial RNA granules, where they regulate RNA stability and translation efficiency. Once matured, RNA not only stays in the mitochondrial matrix but can also be transported to the cytoplasm and nucleus. This review summarizes recent advances in mitochondrial DNA transcription and post-transcriptional processing and modification, with an emphasis on the underlying mechanisms and their sub-mitochondrial localization. It further focuses on the roles of mitochondrial RNA modifications in regulating RNA stability, translation efficiency, and gene expression, and discusses the distribution and transport mechanisms of mature mitochondrial RNA. This review aims to clarify the regulatory mechanisms of mitochondrial gene expression and to provide new insights into the mechanisms underlying mitochondrial dysfunction-related diseases and potential therapeutic targets.

Dysregulation of cholesterol homeostasis plays a pivotal role in tumorigenesis, progression, and immune evasion. This review summarizes the core regulatory mechanisms of intracellular cholesterol metabolism, including biosynthesis mediated by sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), low-density lipoprotein receptor (LDLR)-dependent exogenous uptake, ATP-binding cassette transporter A1/G1 (ABCA1/ABCG1)-driven efflux, and esterification catalyzed by acyl-CoA:cholesterol acyltransferase 1/2 (ACAT1/2). It further systematically elaborates on the multidimensional regulatory functions of these metabolic pathways within the tumor immune microenvironment (TIME). In the TIME, tumor cells reprogram their own and surrounding immune cells’ cholesterol metabolism to establish an immunosuppressive milieu. Specifically, enhanced ACAT1 activity leads to cholesterol ester accumulation in T cells, impairing receptor clustering and effector function. Oxysterols, such as 25-hydroxycholesterol (25-HC) and 27-hydroxycholesterol (27-HC), modulate macrophage polarization, inhibit dendritic cell (DC) migration, and induce T cell exhaustion via liver X receptor (LXR) signaling. The functional maturation of myeloid-derived suppressor cells (MDSCs) is also regulated by the XBP1-cholesterol axis. Moreover, the antitumor activity of natural killer (NK) cells is negatively regulated by LDLR-mediated cholesterol uptake and the bile acid metabolite iso-lithocholic acid (iso-LCA). Targeting cholesterol metabolism demonstrates significant antitumor potential: statins inhibit the mevalonate pathway; inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) or niemann-pick C1-like 1 (NPC1L1) block cholesterol uptake; and the ACAT inhibitor avasimibe not only directly suppresses tumor growth but also reverses immunosuppressive states. Notably, combining cholesterol metabolism modulators with immune checkpoint inhibitors produces synergistic effects, significantly enhancing antitumor immunity. Therefore, cholesterol metabolism serves not only as a metabolic foundation for tumor cell proliferation but also as a critical metabolic hub regulating TIME function. Its precise intervention holds promise for developing novel and effective combinatorial strategies for cancer therapy.

Gefitinib, a first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), exerts significant therapeutic efficacy in the treatment of non-small cell lung cancer (NSCLC) by selectively targeting mutant forms of EGFR. However, the development of acquired resistance significantly limits its long-term clinical benefits. Cell division cycle 20 (CDC20), a key regulator of cell cycle progression, has been implicated in the tumorigenesis and progression of various malignancies. Nevertheless, its role and underlying regulatory mechanisms in the acquisition of drug resistance in NSCLC remain largely unexplored. This study aimed to elucidate the molecular mechanisms by which CDC20 contributes to gefitinib resistance in NSCLC. Gefitinib-resistant cell lines, HCC827/GR (IC₅₀ 0.05 ± 0.01 μmol/L vs 36.24 ± 6.21 μmol/L) and PC9/GR (IC₅₀ 0.02 ± 0.01 μmol/L vs 25.36 ± 5.57 μmol/L), were established through stepwise drug induction, exhibiting markedly increased IC₅₀ values compared to their parental counterparts. Bioinformatics analysis revealed that the transcriptional level of CDC20 is significantly upregulated in lung cancer tissues and is associated with poor patient prognosis. Western blotting analysis confirmed elevated CDC20 protein levels in the resistant HCC827/GR and PC9/GR cells relative to the parental HCC827 and PC9 cells. To further investigate the functional role of CDC20 in NSCLC gefitinib resistance, CDC20 was knocked out using CRISPR/Cas9 technology. This genetic intervention significantly restored gefitinib sensitivity in resistant cells (IC₅₀ 37.08 ± 6.15 μmol/L vs 10.49 ± 1.83 μmol/L, 7.23 ± 1.55 μmol/L), while concurrently promoting apoptosis and inducing G₂/M phase cell cycle arrest. Conversely, CDC20 overexpression decreased drug sensitivity in parental cells and notably attenuated gefitinib-induced apoptosis and cell cycle arrest. Mechanistically, CDC20 depletion was found to inhibit activation of the PI3K/Akt/mTOR signaling pathway, upregulate pro-apoptotic proteins such as cleaved-Caspase 3 and Bax, and downregulate the anti-apoptotic protein Bcl-2. Collectively, these findings demonstrate that CDC20 mediates gefitinib resistance in NSCLC through modulation of the PI3K/Akt/mTOR signaling pathway, thereby identifying CDC20 as a potential therapeutic target for overcoming resistance to EGFR-targeted therapies.

Tuberculosis (TB) remains a major global public health threat, and the worsening of multidrug-resistant tuberculosis has further intensified the challenges in its prevention and control. Conventional diagnostic methods are limited by their low sensitivity and significant delays, while the introduction of artificial intelligence (AI) technology offers a breakthrough solution for TB control. In terms of diagnosis, AI technologies significantly improve the efficiency of TB screening and enable accurate identification of disease manifestations. Meanwhile, AI also plays an important role in the discovery of TB biomarkers, where it identifies high-performance novel diagnostic markers through the analysis of multi-omics data. In the field of treatment, AI models can predict drug efficacy and the risk of adverse reactions, supporting personalized therapeutic strategies. In drug development, AI accelerates the discovery of drug targets and the screening of compounds for tuberculosis, and even enables the de novo design of novel drugs. This review summarizes the latest applications of AI in the diagnosis, treatment, and drug development of tuberculosis, aiming to clarify the current role of AI in TB control and outline future research directions.

Intracerebral hemorrhage (ICH) is a subtype of hemorrhagic stroke with extremely high mortality and disability rates, caused by the spontaneous rupture of non-traumatic cerebral blood vessels and the subsequent infiltration of blood into brain tissue. Due to its high incidence and poor long-term prognosis, it imposes a heavy burden on patients’ lives and the economy. Therefore, minimizing the neurological deficits after injury has become an urgent problem to be solved. In recent years, the role of extracellular vesicles (EVs) in mediating complex intercellular signaling and maintaining brain tissue homeostasis has attracted attention. Most EVs have good biocompatibility, stable membrane structure, low immunogenicity, and the ability to carry various bioactive molecules, providing favorable conditions for their successful passage through the blood-brain barrier and targeted regulation of brain cells. This article systematically reviews the biological and functional characteristics of EVs, thoroughly analyzes their dual regulatory roles in the pathophysiological process of cerebral hemorrhage, interprets the application potential of EVs as biomarkers for dynamic disease monitoring in the diagnosis of cerebral hemorrhage, and highlights the latest progress and improvement strategies of EVs as drug delivery and gene editing vehicles. This review aims to provide theoretical support for the precise clinical application of EVs in the diagnosis and treatment of cerebral hemorrhage.

Exendin-4 (Exe), a glucagon-like peptide-1 (GLP-1) receptor agonist, has a protective effect on pancreatic β cells; however, its underlying mechanism is not well understood. In this study, Exendin-4 exhibited a higher antioxidant ability and protected MIN6 cells from high glucose-induced oxidative damage by reducing reactive oxygen species (ROS) production (P < 0.01), and maintaining mitochondrial function in pancreatic β cells. The beneficial effects of Exendin-4 included increased cell viability (P < 0.05) and insulin secretion (P < 0.05), as well as improved mitochondrial membrane potential (MMP) (P < 0.01) and ATP levels (P < 0.05). Additionally, Exendin-4 inhibited lactate dehydrogenase (LDH) activity (P < 0.001) and reduced intracellular malondialdehyde (MDA) levels (P < 0.01), and boosted the activities of antioxidant enzymes such as superoxide dismutase (SOD) (P < 0.01) and catalase (CAT) (P < 0.01). Glutaredoxins (Grxs) were identified as glutathione (GSH)-dependent oxidoreductases, and the Grx/GSH system is commonly referred to as the cellular antioxidant system acting in the defense of pancreatic β cells against oxidative stress and the mitochondrial damage. Our findings revealed that Exendin-4 significantly enhanced the protein expression levels of glutaredoxin 1 (Grx1), glutaredoxin 2 (Grx2) and glutathione reductase (GR) (P < 0.05), and improved the GSH/GSSG ratio (P < 0.01) and NADPH/NADP⁺ ratio (P < 0.05). These results indicate that Exendin-4 improved the function of pancreatic cells under high glucose condition. The underlying mechanism involves increasing the expression levels of key proteins in the glutaredoxin system and inhibiting the dysfunction of the Grx/GSH system, thereby reducing mitochondrial oxidative damage and functional disorders.

Premature ovarian insufficiency (POI), also known as premature ovarian failure (POF), is one of the major causes of female infertility. Its incidence has been increasing year by year, seriously affecting women’s reproductive health and becoming an increasingly serious public health problem worldwide. The pathogenesis of POI is complex and may be related to genetic, immune and environmental factors, but in recent years, oxidative stress (OS) has received widespread attention as a key factor that can affect the function of ovarian granulosa cells (GCs), which can lead to the occurrence of POI. Reactive oxygen species (ROS) regulate the proliferation, survival and apoptosis of GCs through multiple signaling pathways, such as PI3K-Akt, MAPK, TGF-β/Smad, Notch, etc. AMPK and mitochondrial autophagy play important roles in attenuating the ROS damage and protecting the ovarian function. Excessive ROS disrupts the autophagy and lysosomal functions, leading to the accumulation of intracellular waste products, thus affecting the physiological function and endocrine stability of GCs. In addition, OS can increase the risk of POI by affecting hormone synthesis and disrupting the function of GCs, leading to an imbalance in estrogen and progesterone levels. Herein we review the mechanism of OS in POI, explore how OS affects ovarian decline through the regulation of signaling pathways and cellular functions, and provide a theoretical basis for the clinical treatment of POI, which in turn provides new research ideas for its early diagnosis and prevention.

Ideological and political education within university courses is essential for fulfilling the institution’s core mission of cultivating virtue through education. As artificial intelligence technology increasingly penetrates the educational domain, the need to reform and innovate curriculum-based ideological and political instruction has become pressing. Generative Artificial Intelligence (Generative AI), a significant subset of AI, presents new avenues for overcoming teaching challenges and transforming educational methodologies through its extensive database and advanced interactive understanding and dialogue capabilities. This study investigates the application of Generative AI in the ideological and political education of the course “Clinical Immunological Testing Techniques,” aiming to improve the efficacy of moral education in teaching and to achieve a seamless integration of knowledge transfer, skill development, and value guidance. Utilizing Generative AI technology, we intelligently extracted and reconstructed ideological and political content from the curriculum, creating a human-AI collaborative teaching model structured around “precise pre-class preparation—collaborative in-class inquiry—post-class reflection and internalization”. Students from the Class of 2021 (n=219) and Class of 2022 (n=217) in the Medical Laboratory Science program were designated as the control and research groups, respectively. Teaching interventions were conducted under uniform conditions, including the same teaching teams, course content, and assessment criteria. The effectiveness was evaluated by comparing the two groups across various metrics: academic performance in professional knowledge, practical skills, learning behavior data (encompassing classroom participation and AI interaction frequency), and questionnaire responses. Results indicated that the research group significantly outperformed the control group in professional knowledge and practical skills (P<0.001). Learning behavior data revealed higher AI interaction frequency and discussion participation rates in the research group. Moreover, 89.2% of students expressed a positive attitude towards AI-enhanced ideological and political education. In conclusion, the implementation of Generative AI in “Clinical Immunological Testing Techniques” has contributed to enhancing students’ professional competence and practical abilities, enabling the precise integration of ideological elements, and facilitating the subtle infusion of value guidance, thus providing a reproducible and practical model for the reform of ideological and political education in medical courses.

Endometrial carcinoma (EC) is one of the most common malignancies of the female reproductive system, and its incidence continues to rise. While diagnostic and therapeutic approaches have advanced, the prognosis for patients with advanced-stage remains poor. Emerging treatment strategies, particularly targeted therapies, offer new hope and underscore the urgent need for novel therapeutic targets. The ubiquitin-proteasome system (UPS), a key pathway for intracellular protein degradation, significantly influences cancer progression by regulating key proteins in oncogenic pathways through ubiquitination or deubiquitination. microRNAs (miRNAs) are a class of small RNAs widely present in eukaryotic cells that regulate gene expression and the cell cycle by binding to specific mRNAs and inhibiting their posttranscriptional expression. They can also directly target key ubiquitin ligases or deubiquitinating enzymes (DUBs), affecting downstream pathways. This review discusses how ubiquitin ligases or deubiquitinating enzymes regulate related proteins in several signaling pathways in EC and explores the mechanisms by which abnormally expressed microRNAs influence oncogenesis by targeting mRNAs of proteins in the UPS. By elucidating the roles of dysregulated ubiquitination and deubiquitination from RNA and protein perspectives, this study identifies potential therapeutic strategies and provides new insights into molecular diagnostic markers and treatments for EC.