Two ways of application in human for the results of aging mechanism are geriatric medicine and longevity medicine. After several years research, it has been obtained good results in mice for targeting senescent cells, but a little effective for translation into human being. In this subject, there are review papers from different mechanism on aging and shows prospects in the application of human. In the future study, it may be required to answer basic questions on aging mechanism, especially in the changes of numbers and dynamic states in senescent cells in late life of human. It will play solid foundation in clinic application.

Mesenchymal stem cells (MSCs), with multi-lineage differentiation potential and their potent tissue repair effect, exhibit great application prospects in regenerative medicine and anti-aging fields. However, MSCs inevitably undergo senescence in vivo or ex vivo expansion, leading to a significant decline in their therapeutic potential and increase in safety risks, which have restricted the clinical application of large-scale preparation of MSCs. In recent years, autophagy, as the core intracellular quality control system, its functional status has been identified as a key determinant of the MSC aging process. In senescent MSCs, a general decline in autophagic activity or impairment of autophagic flux is observed. The underlying molecular mechanisms are complex, involving imbalances in multiple key signaling pathways (e.g., persistent activation of mTORC1, decreased activity of AMPK and SIRT1), epigenetic silencing of core autophagy-related genes, and lysosomal dysfunction. This systematic failure leads to the accumulation of damaged organelles and proteins, which is the primary internal driver for the formation of senescent phenotypes, such as proliferation arrest, abnormal differentiation, and the senescence-associated secretory phenotype (SASP). Therefore, targeting autophagy has emerged as a cutting-edge interventional strategy to delay MSC senescence and restore their youthful functions. This review systematically summarizes the crucial roles of autophagy in maintaining MSC functions, deeply analyzes the key molecular mechanism network of autophagy dysregulation during MSC senescence, and focuses on the latest advances in interventional strategies represented by pharmacology, genetic engineering, and biomaterials. We aim to provide new theoretical references and intervention strategies for enhancing the efficacy of stem cell therapy and delaying organismal aging.

As the trend of population aging intensifies, health issues caused by age-related diseases have become increasingly prominent, exerting severe impacts on individual health and socioeconomic development. Extracellular vesicles (EVs) play a crucial role in mediating intercellular communication and regulating cellular functions by transmitting signaling molecules, transporting intracellular components, and modulating immune responses. Owing to their low immunogenicity, high biocompatibility, and ability to cross biological barriers, EVs have emerged as a new generation of targeted therapeutic delivery vehicles for age-related diseases. However, natural EVs exhibit limitations such as low drug-loading efficiency, insufficient targeting capability, and short in vivo circulation time, which severely restrict their clinical applications. In recent years, engineered EVs, with their enhanced drug-loading efficiency, targeting ability, and prolonged in vivo circulation, have provided a novel strategy for the treatment of age-related diseases. This review systematically summarizes the drug loading methods, targeted delivery strategies, and techniques to prolong in vivo circulation of engineered EVs, and elaborates on the current application status of engineered EVs as targeted therapeutic delivery vehicles in age-related diseases. Furthermore, this review synthesizes the common characteristics and differential requirements of engineered EVs as delivery vehicles in the treatment of various age-related diseases, and discusses the opportunities and challenges in their clinical translation, aiming to provide a theoretical basis for engineered EV-based therapy for age-related diseases.

With the accelerating pace of global aging, senescence and its associated diseases have emerged as significant public health challenges. The gut, a crucial organ in the regulation of aging, undergoes a process characterized by a loss of gut microbiota diversity, impaired intestinal barrier function, and disrupted immune regulation. These changes subsequently lead to increased oxidative stress and a systemic inflammatory state, ultimately accelerating overall organismal aging and the onset and progression of various diseases. This review systematically summarizes the mechanisms and potential applications of probiotics in alleviating gut aging. Research indicates that probiotics can mitigate the intestinal aging process via multiple pathways, including enhancing intestinal barrier function, modulating immune and antioxidant activity, regulating gut-brain axis communication, and restoring gut microbiota diversity. Furthermore, this article reviews the clinical applications of probiotics in age-related diseases, such as improving metabolic diseases (e.g., NAFLD) via the “gut-liver axis”, alleviating digestive disorders through microbiome restoration, counteracting musculoskeletal decline via the “gut-muscle/bone axis”, delaying age-related immunosenescence through immune modulation, ameliorating neurodegenerative diseases via the “gut-brain axis”, and slowing skin aging through the “gut-skin axis”. Despite the promising potential demonstrated by existing studies, challenges remain, including strain-specific effects, individual variability, and long-term safety concerns. Future research should integrate multi-omics technologies, personalized intervention strategies, and the development of novel formulations to promote the precise application of probiotics in the field of healthy aging. This review aims to provide a theoretical reference and future perspectives for mechanistic research and clinical practice concerning probiotic interventions for gut aging and related diseases.

Nucleic acid isothermal amplification technology has been widely used in many fields such as DNA nanotechnology, data storage and biosensing, which is of great significance to the development of biology. Because it can achieve nucleic acid amplification at a constant temperature without thermal cycling, it can be adapted to different application scenarios. In addition, it can better meet the needs of modern molecular detection technology in terms of rapidity and simplicity, which can provide an important application value for early diagnosis in clinical medicine. In this article, we summarize the principles of several enzyme-based isothermal amplification techniques, including rolling circle amplification (RCA), strand displacement amplification (SDA), loop-mediated isothermal amplification (LAMP), recombinase polymerase amplification (RPA), and primer exchange reaction (PER), as well as non-enzymatic isothermal amplification techniques, such as hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA), along with their applications in nucleic acid detection. This review focuses on the latest advances and future outlooks, aiming to contribute to the iterative development of isothermal amplification in this field.

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.

Helicobacter pylori (H. pylori) plays an extremely important role in mediating gastric mucosal damage, and studies have shown a significant association between mid to high altitudes and chronic gastritis. Here we aim to investigate the effects of hypoxia-associated H. pylori infection in modulating pathological inflammatory injuries in gastric epithelial cells and its potential mechanisms. Tissues of gastric antrum mucosa were collected from uninfected and infected H. pylori patients in plains and plateau areas, and cellular and human gastric organoid models of hypoxia-associated H. pylori infection of gastric epithelium were constructed in vitro, and the effects of hypoxia-associated H. pylori infection on pathological inflammatory injuries and hypoxia-inducible factor-1α (HIF-1α) expression in gastric mucosa were detected using enzyme-linked immunosorbent assay (ELISA), immunohistochemical staining, immunofluorescence staining, real-time fluorescence quantitative PCR(RT-qPCR) and Western blotting. The results revealed that hypoxia-associated H. pylori infection induced up-regulation of HIF-1α expression in human gastritis clinical samples in vivo and in gastric epithelial cells and gastric organoid models in vitro (P<0.05). Next, signaling pathway screening was performed in an in vitro cell model to explore the underlying mechanism, and it was found that the expression of HIF-1α was significantly inhibited when the PI3K/AKT signaling pathway was blocked (P <0.05). Finally, preliminary validation of downstream target genes regulated by HIF-1α using bioinformatics and transcriptome sequencing suggested that Solute Carrier Family 2 Member 1 (SLC2A1) is one of the important downstream target molecules regulated by HIF-1α (P＜0.05). The results suggest that hypoxia-associated H. pylori infection induces the up-regulation of HIF-1α expression via the PI3K/AKT pathway, and the latter promotes the up-regulation of SLC2A1 expression, which suggests that the level of glycolysis in the microenvironment of the gastric mucosa may be more active in the patients infected with H. pylori in plateau areas. This provides new theoretical support for the study of the mechanism of pathological inflammatory injury of gastric epithelial cells in hypoxia-associated H. pylori infection, and also provides new ideas for the prevention and treatment of hypoxia-associated H. pylori infection-associated gastritis.

Heat shock proteins (HSPs) are a class of stress proteins widely found in various organisms, which are rapidly synthesized when the body is exposed to adverse stimuli and play a protective role.DNAJC5 is a member of the HSP40 family of heat shock proteins, and the aim of this paper is to investigate its role in bacterial infections of Rana dybowskii. In this study, we obtained the full-length cDNA sequence of DNAJC5 from Rana dybowskii by homologous cloning and analyzed it bioinformatically; then we constructed an inflammation model by injecting Aeromonas hydrophila (Ah) into Rana dybowskii; The transcript levels of DNAJC5 in different tissues under Ah stress were detected by real-time quantitative PCR (qRT-PCR), and the dynamic changes of DNAJC5 protein at different infection time points were analyzed by western blot. The results showed that the CDS region of the DNAJC5 gene of the Rana dybowskii was 600 bp in length (NCBI accession number: OQ944896), encoding 199 amino acids, with a conserved structural domain of DNAJ, which belongs to a typical member of the HSP40 family. The qRT-PCR results showed that DNAJC5 was expressed in different tissues, and under normal physiological state, the DNAJC5 gene was most highly expressed in the spleen, followed by the liver; The peak expression of DNAJC5 mRNA in the liver, spleen, lung, kidney, skin and stomach was reached at 12h after infection with Ah (P <0.05), and that in the heart and muscle tissues was reached at 6h (P <0.05). Western blot analysis showed that DNAJC5 protein increased 1.39 and 1.13 times in liver and spleen, respectively (P >0.05), showing a dynamic expression trend of first increase and then decrease, with the consistency of both transcription and translation levels. In summary, the DNAJC5 gene may be involved in the immune response process against Ah infestation, and the results of this study provide a theoretical basis for further exploration of the mechanism of resistance to bacterial infection in amphibians.

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.

Insulin resistance (IR) serves as a common pathological feature for a variety of metabolic disorders, such as type 2 diabetes mellitus (T2DM), metabolic syndrome, and nonalcoholic fatty liver disease [ (NAFLD, or as recently named as ‘metabolic-associated fatty liver disease’ (MAFLD)], etc. Dysregulation of insulin signaling pathway in the liver is of critical importance for insulin resistance, while the underlying regulatory metabolism remains to be further studied. Human antigen R (HuR), a crucial RNA-binding protein, maintains cellular metabolic homeostasis through post-transcriptional regulation. In this study, a hepatocyte-specific HuR knockout mouse model (HuR cKO) was utilized to investigate the impact of hepatic HuR deficiency on insulin sensitivity and related signaling pathways. We found that HuR cKO mice developed significant insulin resistance after 8 weeks of high-fat diet feeding, as evidenced by elevated fasting blood glucose and reduced insulin sensitivity. The deficiency of HuR significantly reduced insulin receptor substrate 2 (IRS2) protein levels and subsequently impaired downstream AKT2 and GSK3β signaling activities. Mechanistically, HuR stabilized IRS2 mRNA through associating with its 3′ UTR (3′ untranslated region), subsequently promoted IRS2 protein expression. This study elucidates a novel post-transcriptional mechanism by which hepatocyte HuR regulates insulin resistance, providing new insights for potential therapeutic strategies against metabolic diseases associated with insulin resistance.

The Yangtze finless porpoise (Neophocaena asiaeorientalis) is a freshwater cetacean species endemic to China, with a population of approximately 1 200, and is classified as “critically endangered”. Significant differences in growth and development exist between male and female Yangtze finless porpoises. To investigate the molecular regulatory mechanisms underlying these sexual dimorphisms, this study focuses on non-coding RNAs (ncRNAs)—key regulators of gene expression that play crucial roles in sex determination and differentiation. Using whole transcriptome sequencing technology, a systematic analysis was conducted on the differential expression profiles and functional annotations of ncRNA in the blood of male and female Yangtze finless porpoises. We identified 205 differentially expressed circRNAs (87 upregulated in females, 118 downregulated), 122 lncRNAs (54 upregulated, 68 downregulated), and 48 small RNAs (32 upregulated, 16 downregulated). Enrichment analysis demonstrated that these ncRNAs collectively modulate sexual differentiation via core processes such as energy metabolism (ATP binding, the PI3K-Akt pathway), immune regulation and signal transduction. Consistency between quantitative PCR results of key downstream genes (MAPK1, IRS1, ALAD, and C1QC) and sequencing data provided experimental support for the regulatory roles of these ncRNAs. This study systematically elucidates the multidimensional regulatory network of ncRNAs in the sexual differentiation of the Yangtze finless porpoise, providing a molecular-level theoretical basis for understanding its physiological differentiation mechanisms and aiding in the development of conservation strategies for this endangered species.

The ubiquinol-cytochrome c reductase complex chaperone (BCS1L), a key regulator of the mitochondrial complex III assembly, plays a critical role in mitochondrial genetic disorders and prostate cancer-related fatigue, but its functional mechanisms in colon adenocarcinoma (COAD) remained unclear. This study systematically investigated the clinical significance and molecular mechanisms of BCS1L in COAD through integrated multi-omics analysis and functional experiments. Bioinformatics analysis of public databases revealed that BCS1L expression was significantly up-regulated in colon cancer tissues (P<0.05), with high expression correlating with poor prognosis and patient age. Functional enrichment analysis demonstrated a correlation of high BCS1L expression groups with organic anion/carboxylic acid transport pathways. The immune cell infiltration analysis revealed an increased proportion of regulatory T cells (Treg) cells in the high BCS1L expression group. The mutation profile results showed that the mutation frequencies of genes such as PCLO, ABCA13, LRP1B, FAT3, HYDIN, and SOX9 were significantly higher in the high BCS1L expression group (all P<0.05). Experimental validation confirmed that BCS1L knockdown significantly inhibited cell proliferation, clonogenicity, and migration in COAD (all P<0.05). Collectively, these findings demonstrate that BCS1L plays a pivotal role in promoting cell proliferation and migration by modulating transport pathways and facilitating the formation of an immunosuppressive tumor microenvironment in COAD.

Biochemistry is a crucial foundational discipline in medical education, yet students often struggle with its complexity due to the intricate structures of biomolecules and biochemical reactions, leading to apprehension about difficulties. With the diversification of teaching methods in higher education, the Scientific Song (SS) approach has gradually been incorporated into curricula, with biochemical songs gaining attention as an innovative pedagogical tool. This paper systematically explores the theoretical foundations of emotional engagement and learning motivation, analyzing the effectiveness of biochemical songs in fostering emotional stimulation and enhancing motivation in biochemistry education. This paper employs original biochemical songs in classroom teaching, proposing a three-tier “Affection-Cognition-Behavior” instructional strategy model based on the SS framework. Key elements include content precision (balancing science and art), adaptability to student levels (tiered difficulty), closed-loop instructional design (input-deconstruction-output), and deep student co-creation (lyric adaptation, competitions) to boost engagement and creativity. The study also highlights critical considerations for implementing biochemical songs: ensuring scientific accuracy through expert review and annotated lyrics, avoiding style over substance, precise alignment with diverse learning needs and objectives, creating deep learning cycles to prevent superficial entertainment, and motivating students to transition from passive recipients to active creators to drive intrinsic motivation—guarding against misplaced priorities or overcorrection. This research not only enriches biochemistry teaching methodologies but also provides practical strategies emphasizing the role of emotion and motivation in discipline-specific education, offering both theoretical and practical value.