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.

Gastric cancer (GC) is a pervasive malignant tumor with a high incidence rate, and its mortality in late stages poses a significant threat to global public health. Despite advancements in diagnosis and treatment, the prognosis for advanced GC remains poor. The progression of GC is closely associated with immune system dysfunction, particularly the role of the immune checkpoint programmed death ligand 1 (PD-L1), which is a key mediator of immune evasion and a promising target for immunotherapy. The ubiquitin proteasome system (UPS), including ubiquitinases and deubiquitinases, is primarily responsible for the degradation of programmed death 1 (PD-1)/PD-L1) proteins and plays an indispensable role in the malignant progression and metastasis of GC. This review synthesizes research on GC immunity, the role of DUBs in regulating PD-L1 stability and immune evasion, and major immunotherapies such asimmune checkpoint inhibitors (ICIs), with a focus on the promising DUB inhibitors which may improve the efficacy of GC immunotherapies. In recent years, various ICIs have been widely used in immunotherapy, significantly improving the clinical prognosis of cancer patients. However, immunotherapy also faces many challenges. Meanwhile, multiple DUBs have been shown to directly bind to PD-L1, inducing its deubiquitination and stabilization, leading to the development of malignant tumors. The efficacy of ICIs is closely related to PD-1/PD-L1. Therefore, inhibiting these DUBs can make tumor cells sensitive to immune surveillance and enhance the effectiveness of ICIs. Therefore, in-depth exploration of the combination therapy of DUBs inhibitors and ICIs is of great significance for improving the prognosis of GC.

Post-translational modifications (PTMs) are crucial molecular mechanisms that regulate tumor biology. In addition to traditional modification types, novel PTMs such as SUMOylation, lactylation (Kla), palmitoylation (Pal), crotonylation (Kcr), and succinylation (Ksucc) are increasingly being elucidated in the context of gastrointestinal cancer. Evidence indicates that sumoylation promotes the progression of stomach neoplasms by regulating epigenetic modifications mediated by NSUN2 K516 site and stabilizing PD-L1-associated immune checkpoints. It also facilitates the invasion and metastasis of colorectal neoplasms through mechanisms involving the regulation of USP48 K258 site and influencing DNA damage repair. Lactylation drives the proliferation of stomach neoplasms tumor cells by activating the Hippo pathway through non-histone lactylation of YAP/TEAD1 or by inducing immune-inhibitory mesenchymal stem cell recruitment in stomach neoplasms via a metabolism-epigenetics coupling mechanism that activates the VCAM1-AKT pathway. Palmitoylation promotes the progression of colorectal neoplasms by stabilizing β-catenin protein and drives the malignant progression of stomach neoplasms by stabilizing NRF2. This review systematically summarizes the molecular mechanisms by which these novel PTMs contribute to the initiation, progression, and treatment resistance of gastrointestinal cancer. Furthermore, it discusses the clinical translational potential of therapeutic strategies targeting the SENP1-YBX1 axis and lactyltransferase inhibitors, providing a theoretical foundation for the development of novel biomarkers and the reversal of treatment resistance.

Histone lysine crotonylation (Kcr), a novel acylation modification discovered in 2011, plays significant roles in gene expression regulation, cellular development, and disease treatment. Over the past decade, the enzyme systems regulating Kcr modification have been identified, including crotonyltransferases, decrotonylases, and reader proteins that recognize crotonylated modifications. Kcr exerts crucial functions in various physiological processes such as gene transcription, DNA damage repair, spermatogenesis, stem cell differentiation, and protein regulation, while abnormal Kcr modifications have been closely associated with disease pathogenesis. This review systematically summarizes the discovery process, regulatory factors, and biological functions of Kcr, providing a theoretical foundation for further exploration of the functional mechanisms underlying protein crotonylation modifications.

Ubiquitination is a reversible post-translational modification that regulates protein stability, localization and interaction, thereby influencing key cellular processes including cell cycle, signal transduction and transcription. Deubiquitinating enzymes (DUBs) remove ubiquitin chains from their substrates to modulate protein function and sustain cellular homeostasis. As a functionally versatile DUB family member, Ubiquitin-specific protease 27X (USP27X) participates in diverse biological processes, e.g., cell proliferation, neural development, antiviral defense, innate immunity, and its dysfunction is linked to X-linked intellectual disability (XLID). Notably, USP27X acts in a context-dependent manner, either as a tumor promoter or suppressor in cancer, which is determined by cell type and microenvironment. This review will outline the structural features of USP27X and elaborate its roles in chromatin remodeling, gene expression, neurodevelopment and immune regulation, highlighting its involvement in cancer and other diseases, as well as exploration of its potential as a therapeutic target.

Kidney diseases pose a significant threat to global health due to its high morbidity and mortality rates. Renal fibrosis represents a common pathological endpoint in the progression of various chronic kidney diseases, and effective interventions remain limited. In recent years, protein lactylation, a novel post-translational modification, has emerged as a research hotspot at the intersection of metabolism and epigenetics. This modification utilizes lactate as a substrate to covalently modify lysine residues on both histone and non-histone proteins, playing a crucial role in regulating gene transcription and protein function. Here we review recent advances in lactylation modification within acute kidney injury, diabetic nephropathy, and chronic kidney disease, focusing on its role in promoting disease pathogenesis through mechanisms such as regulating inflammatory immune responses, mitochondrial function, and programmed cell death. Current research still faces challenges, including a lack of specificity in targets, unclear mechanisms, and limited intervention strategies. Future studies could leverage the multi-target advantages of traditional Chinese medicine to explore integrative approaches, providing new insights for the prevention and treatment of kidney diseases.

Antimicrobial resistance (AMR) has emerged as a serious global public health challenge, and traditional antibiotic targets are gradually losing efficacy, highlighting the urgent need for novel breakthroughs. Iron-sulfur (Fe-S) clusters, an evolutionarily ancient and highly conserved class of cofactors, are widely involved in energy metabolism, genome stability maintenance, and oxidative stress response regulation. Within the host, iron limitation and intense oxidative pressure directly disrupt Fe-S homeostasis, whereas bacteria employ assembly systems such as ISC system (iron-sulfur cluster assembly system, ISC) and SUF system (sulfur mobilization system, SUF) to restore Fe-S clusters and thereby sustain resistance. Recent studies demonstrate that Fe-S homeostasis is not only essential for bacterial survival but also regulates antibiotic resistance through transcription factors such as IscR and SoxR. Targeting Fe-S metabolism can exacerbate endogenous ROS imbalance, weaken bacterial defenses against antibiotics and host immunity, and restore the activity of conventional antimicrobials. This review highlights the central role of Fe-S clusters at the intersection of bacterial resistance and oxidative stress, and proposes that combining Fe-S targeted interventions with conventional antibiotics may offer a promising strategy against antimicrobial resistance.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is ranked first in chronic liver diseases in China, and the pathogenesis has not been fully elucidated. The aim of this study was to investigate the role of the mTOR signaling pathway (including mTORC1 and mTORC2) in the regulation of lipid metabolism in hepatocytes and its molecular mechanism. Firstly, the lipid accumulation model induced by oleic acid (OA) was established by using mouse hepatocytes AML-12 as a model. The results of CCK8 showed that 0.4mmol/L OA was not toxic to cell growth, and the results of oil red O staining and TG content showed that OA treatment could significantly promote intracellular lipid accumulation. Western blotting results showed that OA treatment could activate the mTORC1 signaling pathway. Then, mTORC1 specific inhibitor rapamycin, agonist MHY1485, and siRNA-mediated Raptor and Rictor gene silencing techniques were used to analyze mTOR signaling pathway activity, lipid synthesis-related genes (PPARG, DGAT1, GPAT4, ACSL1) expression and triglyceride (TG) metabolism by Western blotting, RT-qPCR, and TG content detection. The results showed that rapamycin inhibition or Raptor silencing could reduce mTORC1 pathway activity. Reduce lipid synthesis-related gene expression and TG contents; the activation of mTORC1 by MHY1485 further aggravates lipid deposition. In addition, silencing Rictor inhibited the mTORC2 pathway, which also reduced p-AKT expression, TG contents and lipid synthesis gene transcription levels. In summary, this study confirmed that mTORC1 and mTORC2 signaling pathways were activated in the OA-induced hepatocyte lipid accumulation model, and jointly up-regulated the expression of lipid synthesis-related genes (PPARG、DGAT1、GPAT4、ACSL1), positively regulated TG synthesis, thereby promoting lipid deposition in hepatocytes.

Glutaredoxin 2 (Grx2), a crucial endogenous antioxidant protein, plays a significant role in maintaining cellular redox homeostasis and mitochondrial function. To investigate the effects of Grx2 on oxidative stress and mitochondrial damage in pancreatic islet cells induced by high glucose, the mouse pancreatic β-cell line MIN6 was exposed to glucose concentrations of 33mmol/L for 48h. CCK8 assays and measurements of cellular insulin contents demonstrated that Grx2 can enhance cell viability suppressed by high glucose and increase insulin release (P<0.01). Measurements of cellular ATP levels and mitochondrial membrane permeability transition pore (MPTP) fluorescence revealed that Grx2 can increase intracellular ATP levels and inhibit the opening of the MPTP in MIN6 cells induced by high glucose (P<0.01). Reactive oxygen species (ROS) intensity and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio assays confirmed that Grx2 exhibits distinctly antioxidant property (P<0.01). After Grx2 treatment, the malondialdehyde (MDA) and lactate dehydrogenase (LDH) content were reduced (P<0.01), the superoxide dismutase (SOD) and catalase (CAT) levels were increased (P<0.01). Western blotting showed that Grx2 treatment could upregulate the protein expression levels of Grx1 (P<0.05) and Grx2 (P<0.01). Taken together, Grx2 can protect the function of pancreatic β cells by reversing the high glucose-induced suppression of antioxidant proteins Grx1 and Grx2, as well as inhibiting oxidative stress and mitochondrial damage caused by high glucose levels.

Nanoplastics/microplastics (NP/MPs), as emerging global contaminants, pose serious threats to ecological systems and human health. Exposure to NP/MPs has been confirmed to be closely associated with gastrointestinal injuries; however, the specific molecular mechanisms underlying NP/MP-induced duodenal damages remain poorly understood. This study aimed to employ an ICR mouse model, using NP/MPs of different sizes (0.08μm, 1μm, and 10μm), to conduct acute (24h) and subacute (28-days) exposure protocols, in order to clarify the primary exposure routes, in vivo distribution characteristics of polystyrene NP/MPs, their effects on duodenal structure and function, and to explore the underlying molecular mechanisms. Acute exposure (250mg/kg, 24h) showed that NP/MPs administered by oral gavage led to the highest accumulation in the abdominal cavity, followed by drinking water and intraperitoneal injection. The accumulated particles were retained and enriched within the small intestinal villi, with a more pronounced enrichment observed for smaller-sized particles. Subacute exposure (50mg/kg for 28d) revealed duodenal structural disruption and reduced goblet cell counts via hematoxylin-eosin (H&E) and alcian blue-periodic acid Schiff (AB-PAS) staining, with no significant particle size-dependent effect observed. Immunofluorescence and Western blotting analyses consistently showed that exposure to NP/MPs of all three sizes significantly reduced the expression of key intestinal tight junction proteins (claudin-1, occludin, and ZO-1) compared to the control group (P < 0.05). Despite this reduction, no particle size-dependent differences in gene expression were observed among the treatment groups. Immunohistochemistry showed upregulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3), interleukin-1β (IL-1β), and interleukin-18 (IL-18) expression. Immunohistochemistry and Western blotting analyses further indicated that the pyroptosis pathway was activated, as evidenced by increased expression of cleaved caspase-1, cleaved caspase-3 (P < 0.001), GSDMD-NT, and GSDME-NT (P < 0.05), suggesting the involvement of the pyroptosis pathway in duodenal injury. This effect did not exhibit a clear size-dependent relationship among the different particle size groups. These results indicate that NP/MPs primarily accumulate in the small intestine via oral exposure, potentially triggering NLRP3-mediated pyroptosis to drive duodenal injuries. Our study provides experimental evidence for understanding the intestinal toxicity mechanisms of NP/MPs and holds scientific significance for assessing their health risks and formulating corresponding protective strategies.

This study focused on elucidating the lignocellulose degradation mechanism of Pholiota adiposa strain YAHS, aiming to provide theoretical basis and microbial resources for straw biorefining. Using the aniline blue-guaiacol plate screening method, 11 fungal strains were isolated from the Loess Plateau of northern Shaanxi. The highly efficient degrading strain P. adiposa YAHS was identified through DNS-based enzyme activity assays for cellulase and ligninase, combined with ITS sequence analysis. Whole-genome sequencing was performed using a hybrid approach integrating Illumina NovaSeq and Nanopore MinION platforms. Transcriptome-wide differential gene expression analysis was conducted via DESeq2, and untargeted metabolomics was carried out using UPLC-QTOF-MS. Multi-omics data were integrated to dissect the degradation pathways. Results showed that the genome of P. adiposa YAHS is 55.2 Mb in size, encoding 719 carbohydrate-active enzymes (CAZymes), with glycoside hydrolases (GHs) accounting for 37.4%. Multi-omics analysis revealed that this strain degrades lignocellulose into carbohydrates such as monosaccharides, oligosaccharides, and sugar alcohols through key enzymatic genes (e.g., exoglucanase, β-glucosidase, β-xylosidase, β-mannanase, monooxygenase) and metabolic pathways (e.g., sucrose/starch metabolism, fructose/mannose metabolism, anthranilate degradation). We preliminarily elucidated the lignocellulose degradation mechanism of fungi in the genus Pholiota through integrated multi-omics analysis, revealed the critical roles of key cellulolytic enzymes in this process, and provided important microbial resources and theoretical support for the development of novel biorefining technologies.

The platelet-derived growth factor D (PDGF-D), a member of the PDGF family, serves as a potent mitogen for connective tissue cells by specifically binding to and activating the platelet-derived growth factor receptor β (PDGFRβ). It plays critical roles in gastrulation, organogenesis, and early vasculogenesis. Full-length PDGF-D is secreted in an inactive latent form due to the inhibitory effect of its Prodomain on growth factor activity. In this study, we engineered a PDGF-D mutant capable of efficient in vitro activation by replacing the natural proteolytic cleavage site between the Prodomain and growth factor domain with a human rhinovirus 3C protease (HRV 3C)-specific recognition sequence (LEVLFQ↓GP). Following transfection of recombinant plasmids into HEK-293T cells, the PDGF-D mutant protein was successfully secreted into the culture supernatant and purified via Strep-Tactin affinity chromatography. Upon 3C protease cleavage, the released growth factor domain can induce tyrosine phosphorylation of the PDGFRβ receptor. In this study, by designing the protease cleavage site, we achieved efficient expression and controllable activation of latent PDGF-D in the eukaryotic system. The engineered, activity-controllable in vitro PDGF-D provides crucial technical support for studying the molecular mechanisms of PDGF-D interaction with its receptor.

Bovine viral diarrhea virus (BVDV) is a single-stranded positive-sense RNA virus. It contains one large open reading frame (ORF) that encodes a polyprotein with a molecular weight of approximately 449 kD, and has untranslated regions (UTRs) at both ends, namely the 5′ untranslated region (5′-UTR) and the 3′ untranslated region (3′-UTR). BVDV infection may cause respiratory and gastrointestinal tract infections, mucosal disease, reproductive failure and persistent infection in cattle, which has produced significant economic losses for the cattle industry. To establish a rapid detection method for BVDV, a LAMP-Ago method was developed with LAMP primers and gDNAs designed for BVDV 5′-UTR sequence, and the reaction system was optimized. It showed that the cleavage efficiency was the highest when three gDNAs (gDNA4, gDNA4-1, and gDNA4-2) were used simultaneously. The optimal reaction conditions were as follows: gDNA at 1.875 μmol/L, molecular beacon at 0.5 μmol/L, PfAgo at 10 μmol/L, and a total reaction system of 20 μL. The specificity and sensitivity of the LAMP-Ago method for BVDV detection was tested. The results showed no cross reactivity with bovine enterovirus (BEV), Bovine Coronavirus (BCoV) and bovine rotavirus (BRV), confirming its good specificity. The lowest detection limit was 200 ag/μL. Verification using 38 clinical serum samples revealed that the coincidence rate between this method and PCR detection results was 100%. Since the developed BVDV LAMP-Ago method was based on LAMP reaction, it requires only two temperatures to complete the detection and does not need complex PCR instruments for temperature adjustment, thus having the advantages of simple operation and simple equipment. In addition, this method also has the advantages of high specificity and high sensitivity, which can be used for the rapid diagnosis of BVDV, thus facilitating the prevention and control of BVDV.

Breakthroughs in artificial intelligence (AI) technology have provided innovative pathways for education in biochemistry and related fields. This study targets undergraduate students at Shantou University Medical College and explores a novel teaching model that combines “AI-powered screening, VR-immersive cognition, and molecular dynamics (MD) simulation for dynamic evaluation”. Using the Fascin protein as teaching case, softwares such as PharmGPT, PyMOL, Glide, and GROMACS were introduced. Through case-driven and multidisciplinary approaches, this paradigm yields intuitive and interactive learning experiences for abstract molecular structures and complex dynamics. Results show that this paradigm significantly boosts students' technical proficiency and interdisciplinary thinking. Over 90% of students independently completed complex drug design tasks, showing substantial gains in three dimensions: value cultivation, knowledge construction, and interdisciplinary ability. This teaching paradigm provides a replicable and scalable way for “New Medicine” to cultivate innovative and interdisciplinary talents for meeting the needs of future medicine.

We aim to address longstanding challenges in biochemistry laboratory teaching—such as time-consuming reagent preparation, delayed responses to in-class inquiries, and the high rate of forgetting key operational steps. This study constructed an intelligent Q & A system using the Xi’an Jiaotong University biochemistry laboratory manual as the core knowledge base, integrated with the Deepseek V3 as the large language model. The system adopts a three-tier knowledge base architecture—a fundamental layer, a scenario layer, and a dynamic layer—and, through real-time interaction, supports pre-experiment preparation, in-class guidance, and post-experiment review and consolidation. After one semester of instructional application, the effectiveness of the system was evaluated using laboratory performance scores and questionnaire surveys. The results indicate that the system effectively addresses instructional needs across all phases of the laboratory course—before, during, and after experimentation—and significantly improves preparation efficiency and in-class learning outcomes. In particular, the system substantially reduces the workload of instructors during the preparation stage, provides rapid and responsive answers to students’ questions during class, and enhances students’ operational accuracy and problem-solving success.

The structure and function of proteins are closely related. The structure of a protein determines its function, while functional demands drive the evolution and adaptation of its structure. This dynamic relationship enables proteins to meet diverse biological needs and perform a variety of key biological functions within cells. Structural motifs and domains, as fundamental units of protein structure and function, play a crucial role in the evolution of protein functions. In biochemistry education, the chapter on "protein structure and function" is a core topic, with structural motifs and domains being key concepts. However, these topics are often characterized by their theoretical abstraction and logical complexity, posing significant challenges for both teaching and learning. This paper takes the classic helix-turn-helix (HTH) motif as an example and explores the evolutionary process of structural optimization and functional diversification from a single motif to the homeodomain (HD), then to the interactions between homeodomains and to the functional versatility of the BEN domain. By analyzing this evolutionary process, the paper reveals the important role of structural motifs and domains in the evolution of protein functions and proposes specific design and implementation plans. These plans are intended to provide valuable references for the reform of biochemistry education.

This study systematically evaluates the impact of the “Biochemistry Song Contest” on biochemistry student learning outcomes, based on the data from 628 undergraduates at Sun Yat-sen University. Using propensity score matching (PSM) and meta-analysis methods to control for background variables, we found that participating students achieved significantly higher final exam scores than non-participants (pooled effect size, Cohen’s d = 0.344, 95% CI: 0.087-0.602). The results suggest that extracurricular course-related activities in artistic forms can effectively improve academic performance, and enhance students’ understanding of biochemical concepts, forming a positive feedback cycle of “participation-achievement-recognition.” The study further explores potential long-term effects and challenges, such as the balance between art and science and the control of selection bias. Integrating creative second-classroom formats like the Biochemistry Song Contest into course design helps improve learning outcomes and diversify instructional approaches.