Lactylation is a recently identified post-translational modification (PTM) that modulates gene expression and cellular functions by modifying lysine residues, and plays important roles in processes such as tumorigenesis, immune regulation, and metabolism. However, the regulatory mechanisms underlying lactylation remain largely unclear, particularly regarding the enzymes responsible for adding "writers", removing "erasers", and recognizing "readers" lactyl groups. This review systematically summarizes recent advances in the study of these three types of regulators, highlighting their structural features, mechanisms of action, and biological functions. Moreover, it discusses their roles in the disease contexts, including cancer progression, immune evasion, and metabolic adaptation. By integrating current findings, this article aims to provide a theoretical basis for understanding the biological significance of lactylation and to offer new perspectives for targeting lactylation in disease therapy.

B7-H3, also known as CD276, is a new immune checkpoint discovered in recent years and belongs to the B7 superfamily. It has low or no expression in normal human tissues, but abnormal expression in immune cells and tumor tissues. B7-H3 is related to tumor immunotherapy and plays a dual role of co-stimulation/co-inhibition in tumor microenvironment (TME). Therefore, targeting B7-H3 can achieve accurate tumor immunotherapy, thus enhancing anti-tumor immune responses. As the immune function of B7-H3 in tumors has been widely revealed, targeted drugs have also been developed and have entered preclinical and clinical trials. However, the different forms and functions of B7-H3 in human body are still controversial, the human origin structure has not been analyzed, and its potential receptor has not been confirmed. In this paper, the structure and function of B7-H3, its physiological role in tumor immunity and the research progress of targeted therapy are reviewed. In the future, it is necessary to further explore the exact evidence of B7-H3 in tumor immunotherapy and the challenges and limitations of existing therapies, in order to provide new directions and approaches for drug development targeting B7-H3.

As a tethering complex localized on the Golgi membrane, the conserved oligomeric Golgi (COG) complex is divided into lobes A (COG1-4) and B (COG5-8) and forms a complete hetero-octamer structure through the dynamic linkage of COG1 to COG8. Through coordinated interactions with Rab GTPases, SNARE proteins, and Golgi-associated coiled-coil tethers (CCTs), the COG complex participates in coatomer complex I (COPⅠ)-mediated retrograde transport, coatomer complex II (COPⅡ)-mediated anterograde transport, and various autophagic processes. The functional mechanism of the COG complex includes two models. First, the "disassembly and assembly model", in which lobe A anchors the Golgi membrane, while lobe B binds to the vesicle membrane, and both lobes assemble into the complete COG complex to narrow the distance between vesicle and target membranes. Second, the "docking station assembly model", in which COG complexes cooperate with SNARE, Rab and other molecules to form a stable docking platform, to enhance the stability of SNARE complexes and promote membrane fusion efficiency. Additionally, the COG complex is involved in macroautophagy, the vacuole targeting (Cvt) pathway, and pexophagy. In this review, we introduce the regulatory mechanism of the COG complex in several species, and summarize the factors that have synergetic effects with the COG complex in vesicle transport.

Neural tube defects (NTDs) are a category of severe congenital birth defects that seriously affect the life and health of the fetus. The occurrence mechanism is very complex, involving the complex interaction between genetic factors and environmental factors. In recent years, the increasingly widespread application of proteomics has revealed the key role of histone modifications in epigenetic regulation, especially in the pathogenesis of NTDs. Histone modifications include various types such as histone methylation, acetylation, ubiquitination, homocysteinylation, malonylation, and crotonylation. These modifications affect the expression of key proteins involved in neural tube closure and are crucial for genomic stability during neural tube closure, participating in the occurrence and development of NTDs. Abnormal regulation of these regulations is closely related to the occurrence of NTDs. In addition, during embryonic brain development, histone modifications are easily affected by environmental factors such as maternal metabolite levels and exposure to teratogenic substances. Abnormal maternal metabolite levels can cause abnormal regulation of key gene expression, which affects histone modifications and thereby regulates the abnormal expression of downstream related genes, including genes related to neural tube development, leading to the occurrence of NTDs and other neurodevelopmental diseases. Although there have been numerous studies on the mechanism of NTDs, the exact pathogenesis of NTDs has not yet been fully elucidated. In-depth research on the pathogenic factors and occurrence mechanism of NTDs is of great significance for improving the quality of the birth population and reducing neonatal mortality. This article reviews the research progress in recent years on the occurrence of fetal NTDs caused by abnormal histone modifications mediated by maternal metabolites and provides a prospect for the future research direction. With the aim of revealing the key regulatory function of histone modifications in neural tube development, this review also provides a theoretical basis for further research on the relationship between histone modifications and the occurrence of NTDs, and for the future prevention and treatment strategies of NTDs.

Tripartite motif-containing protein 37 (TRIM37) is a multifunctional protein. It is an E3 ubiquitin ligase that primarily localizes to the peroxisome membrane and centrosome. It plays a crucial role in centrosome assembly, which is essential for spindle formation and the accuracy of chromosome segregation, ultimately affecting cell division. By ubiquitinating a variety of substrate proteins, TRIM37 regulates ubiquitination pathways and influences several key signaling pathways. Notably, it is involved in the activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway and regulates autophagy by phosphorylating transcription factor EB (TFEB) via mTORC1. Furthermore, TRIM37 is integral to inflammatory and immune responses, as well as cell proliferation and apoptosis, through the activation of the nuclear factor kappa B (NF-κB) signaling pathway. It is also implicated in the regulation of other critical signaling pathways, such as Wnt/β-catenin and phosphatidylinositol-3-kinase/Protein Kinase B (PI3K/AKT), particularly in the context of cancer. TRIM37 enhances the proliferation, metastasis, and invasion of tumor cells, including those in gallbladder cancer, renal cell carcinoma, and glioma, and is linked to resistance against certain anticancer drugs. In sum, the diverse and complex functions of TRIM37 underscore its significance in various physiological and pathological processes. This article reviews the biological role of TRIM37 and its association with diseases, focusing on its structure, function, involvement in cell autophagy, and the main signaling pathways. We aim to enhance the understanding of TRIM37-related disease pathogenesis and to identify potential new targets for future therapeutic research.

Lysine-specific demethylase 1 (LSD1), a member of the flavin-dependent amine oxidase family, is a crucial "eraser" of lysine methylation. It reversibly removes methyl groups from histone H3K4me1/2 and H3K9me1/2, thereby regulating gene expression and chromatin function. Located within the nucleus, LSD1 influences various biological processes in tumors, including proliferation, invasion, and metastasis. Previous studies have demonstrated that LSD1 is significantly overexpressed in gynecological cancers such as ovarian cancer, cervical cancer, and endometrial cancer, and its overexpression is closely associated with poor patient survival and unfavorable prognosis. Research indicates that LSD1 may promote tumor cell proliferation, invasion, and metastasis through the PI3K/AKT and mTOR signaling pathways, while also suppressing tumor cell autophagy and immune surveillance, contributing to immune evasion. In cervical cancer, LSD1 interacts with HPV16 E7, facilitating the epithelial-mesenchymal transition (EMT) process. Furthermore, LSD1 inhibitors have shown promising therapeutic potential in animal studies, particularly in restoring the sensitivity of ovarian cancer cells to platinum-based chemotherapy. This review summarizes the molecular mechanisms, functional targets, and associated signaling pathways of LSD1 in gynecological cancers, as well as the mechanisms of action of various LSD1 inhibitors, aiming to provide new insights for targeted therapies in gynecological malignancies.

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.

In recent years, adoptive T cell immunotherapy has become a research hotspot in cancer treatment, in which the directional homing of T cells to tumor tissues is the core of the anti-tumor immune response, which is closely related to good clinical treatment outcomes. However, the infiltration of T cells into solid tumors remains challenging due to the complex tumor microenvironment, tumor vasculature barriers, and loss of chemotaxis signals. This review systematically outlines the migration pathways of T cell homing, including blood homing after intravenous infusion, transvascular endothelial migration, and its infiltration into targeted solid tumor tissues. On this basis, we also explore the regulatory mechanism of T cell homing, especially the synergistic relationship between the chemokine-receptor axis, and the effects of tumor vascular abnormalities, tumor microenvironment (TME)-shaped infiltration barriers, and tumor stromal barriers on T cell homing. In response to the above obstacles, three main strategies to enhance the homing efficiency of T cells are reviewed. First, chemokine receptors (e.g., CXCR2, CXCR6) are modified to match tumor chemotaxis signals, or immune checkpoint molecules (PD-1, LAG-3, SHP-1) are knocked out to reverse T cell exhaustion by CRISPR gene editing or lentiviral transduction technology. Second, targeting the VEGF/VEGFR axis combined with ATCT can promote vascular normalization and improve T cell infiltration. Third, the combination of local therapy (radiotherapy, oncolytic virus) or systemic drugs (chemotherapy, immune checkpoint inhibitors, etc.) can improve the homing of T cells by remodeling tumor TME.These strategies will provide a theoretical basis and research direction for adoptive T cell immunotherapy in the treatment of solid tumors.

The xylitol dehydrogenase (XDH) is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi. In addition to producing xylulose, XDH can also be employed to develop a biosensor for monitoring xylitol concentration. In this study, the gene encoding the thermophilic fungus Talaromyces emersonii XDH (TeXDH) was heterologously expressed in Escherichia coli BL21(DE3) at 16 ℃ in the soluble form. Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column. Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the purified recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD, and is composed of three identical subunits, each with a molecular weight of around 39 kD. The TeXDH strictly preferred NAD⁺ as a coenzyme to NADP⁺. The optimal temperature and pH of the TeXDH were 40 ℃ and 10.0, respectively. After EDTA treatment, the enzyme activity of TeXDH decreased to 43.26% of the initial enzyme activity, while the divalent metal ions Mg²⁺ or Ca²⁺ could recover the enzyme activity of TeXDH, reaching 103.32% and 110.69% of the initial enzyme activity, respectively, making them the optimal divalent metal ion cofactors for TeXDH enzyme. However, the divalent metal ions of Mn²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Co²⁺, and Cd²⁺ significantly inhibited the activity of TeXDH. ICP-MS and molecular docking studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn²⁺ ions and 1 mol/L Mg²⁺ ion. Furthermore, TeXDH exhibited a high specificity for xylitol, laying the foundation for the development of future xylitol biosensors.

Neuroblastoma (NB), the most common type of extracranial solid tumor in children, is characterized by high malignancy and poor prognosis, warranting in-depth investigation. In recent years, microRNAs (miRNAs) have emerged as crucial post-transcriptional regulators playing pivotal roles in tumorigenesis and progression. Building upon this background, the present study specifically focuses on investigatingmiR-3910′s biological functions and underlying molecular regulatory mechanisms in the NB SH-SY5Y cell line. Through bioinformatics analysis and transcriptome sequencing, we identified potential key target molecules of miR-3910, thereby providing genetic targets for the precise diagnosis and effective treatment of NB. In this study, qRT-PCR was employed to measure miR-3910 expression levels in SH-SY5Y cells transfected with mimic negative control and miR-3910 mimic. Compared to the nc group, miR-3910 expression was significantly upregulated in the mimic group (P < 0.01). The CCK-8 assay and scratch wound healing assay were used to quantitatively assess the impact of miR-3910 on cell proliferation and migration. Results showed that cell proliferation significantly increased at 48 h (P < 0.05), and migration ability was markedly enhanced at 48 h (P < 0.01). Flow cytometry was applied to determine the effect of miR-3910 on cell cycle progression, revealing accelerated cell cycle progression, a reduced proportion of G₀/G₁ phase cells (P < 0.01), and a significant increase in S-phase cells (P < 0.05). Integrated bioinformatics analysis and high-throughput transcriptome sequencing predicted key molecular changes in SH-SY5Y cells following miR-3910 overexpression. Transcriptome sequencing and bioinformatics analysis identified six NB-related genes: EIF3CL (EIF3C), RNF103-CHMP3 (VPS24), SULT1A4 (SULT1A4), CORO7-PAM16 (CORO7), H4C12 (Histone H4), and TBC1D3 (TBC1D3A/B/C) (aliases sourced from the GeneCards database). qRT-PCR and Western blotting (WB) results are consistency with sequencing results (P < 0.01). In conclusion, miR-3910 overexpression significantly promotes SH-SY5Y cell proliferation, migration, and cell cycle progression, while uncovering a series of potential key target molecules. These findings provide new insights into the pathogenesis of NB and offer a theoretical foundation and potential intervention targets for molecular-targeted therapy in NB.

The incidence rate of kidney diseases in China has always remained high. At present, the clinical treatment mainly focuses on symptomatic treatment to delay the progression of the disease, and there is a lack of economical and effective treatment methods. MicroRNA plays an important regulatory role in the occurrence and development of diseases. This study aims to explore the role and regulatory mechanism of miR-142a-3p in adriamycin (ADR)-induced renal tubular epithelial cell (TCMK-1) injury, with a focus on its potential as a therapeutic target for ADR nephropathy. First, cell viability was assessed using the CCK-8 kit, and a mouse renal tubular epithelial cell model induced by ADR was established. Subsequently, alterations in miR-142a-3p and its target gene ATG16L1 mRNA levels were quantified using RT-qPCR. Western blotting was used to detect the protein levels of autophagy marker proteins and pyroptosis marker proteins. Monodansylcadaverin (MDC) staining was performed and the autophagy of cells was detected by flow cytometry. The results showed that the relative expression of miR-142a-3p in TCMK-1 cells induced by ADR was increased and the relative expression of its target gene ATG16L1 was decreased (P<0.0001). Western blotting results showed that the levels of p62 (P<0.001) and pyroptosis-related proteins (P<0.001) were increased, while the protein levels of autophagy-related proteins were decreased (P<0.05). The flow cytometry results showed that there was no difference in the mean fluorescence intensity of autophagosomes between the ADR group and the autophagosome inhibitor group (3-MA group) (P>0.05), indicating that after ADR induction, cell autophagy was inhibited and pyroptosis was enhanced. When the expression of miR-142a-3p was inhibited by transfecting miR-142a-3p inhibitor, the relative expression level of the target gene ATG16L1 was restored (P<0.001). Western blotting showed that the protein level of p62 (P<0.01) and pyroptosis-related proteins (P<0.01) were decreased, and the protein level of autophagy-related proteins was restored (P<0.001). Flow cytometry results further indicated that cell autophagy was restored (P<0.0001). In conclusion, ADR targets ATG16L1 through miR-142a-3p to reduce the autophagy level of TCMK-1, and simultaneously activates GSDMD-mediated pyroptosis.

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder characterized by abnormalities in the prion protein (PrP), the most common form of human prion disease. Although Genome-Wide Association Studies (GWAS) have identified numerous risk genes for CJD, the mechanisms underlying these risk loci remain poorly understood. This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline. Utilizing datasets from Protein Quantitative Trait Loci (pQTL) (NpQTL1 = 152, NpQTL2 = 376), expression QTL (eQTL) (N = 452), and the CJD GWAS (NCJD = 4 110, NControls = 13 569), we implemented a systematic analytical pipeline. This pipeline included Proteome-Wide Association Study (PWAS), Mendelian randomization (MR), Bayesian colocalization, and Transcriptome-Wide Association Study (TWAS) to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain. Through PWAS, we identified that the altered abundance of six brain proteins was significantly associated with CJD. Two genes, STX6 and PDIA4, were established as lead causal genes for CJD, supported by robust evidence (False Discovery Rate < 0.05 in MR analysis; PP4/(PP3+PP4) ≥ 0.75 in Bayesian colocalization). Specifically, elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD. Additionally, TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.

Sarcopenia is closely linked to metabolic dysregulation in the elderly and shows a major pathological phenotype of functional decline. Although tyrosine metabolism has been shown to be aberrantly activated in variousaging-related disorders, its regulatory role and quantitative causal relationship with clinical muscle function in sarcopenia remain underexplored. We integrated three independent bulk transcriptomic datasets (total n = 487) and applied linear models for microarray data (Limma) differential expression, gene set enrichment analysis (GSEA) pathway analysis, and weighted gene co-expression network analysis (WGCNA) and identified 33 tyrosine metabolism-related genes. Cross-validation using least absolute shrinkage and selection operator (LASSO) regression, random forest (RF), and support vector machine-recursive feature elimination (SVM-RFE) algorithms highlighted four key regulators: FOXO1, ADH1B, DUSP4, and IDO1. Single-cell RNA sequencing (scRNA-seq) data (n = 24 573 cells) combined with single-cell metabolism scoring (scMetabolism) were used to build cell-level linear regression models linking gene expression to tyrosine metabolic activity (e.g., FOXO1: y = 1.7542x + 0.9345, R² = 0.79). Two-sample Mendelian randomization (MR) analysis was conducted to infer causal effects on muscle strength phenotypes. The results showed that FOXO1 was highly expressed in satellite cells (3.1-fold vs. other cell types, P = 1.4 × 10^-8) and showed a strong positive correlation with metabolic activity. MR analysis indicated that higher FOXO1 expression significantly increased the risk of grip strength decline (β = –0.23, P = 2.1 × 10^-6), whereas IDO1 exhibited a protective causal association (β = 0.17, P = 4.3 × 10^-4). A multivariable risk model based on these four genes achieved an area under the curve (AUC) of 0.86 in an independent validation cohort, outperforming traditional clinical indicators (ΔAUC = 0.12, P = 0.003). In sum, by integrating multi-algorithm feature selection, single-cell quantitative modeling, and genetic causal inference, this study systematically elucidates the central role of tyrosine metabolism in sarcopenia and provides a quantitative framework for molecular subtyping and targeted interventions.

This study aims to isolate and culture primary rabbit spinal cord microvascular endothelial cells in vitro, providing a practical source of test cells for spinal cord injury research. Spinal cord tissue was aseptically extracted from one-month-old rabbits and processed sequentially through mincing, bovine serum albumin density gradient centrifugation, mesh filtration, and type Ⅱ collagenase digestion to obtain purified spinal cord microvascular segments. The microvascular segments were homogeneously mixed with an apprapriate volume of M199 complete culture medium and seeded into a culture dish for primary culture. Throughout the culture period, cell growth performance were continuously observed and recorded. Additionally, immunocytochemical staining was performed to evaluate the expression of factor Ⅷ-related antigen. The results showed that after 24 hours of inoculation, a small amount of endothelial-like cells were observed to emerge from the spinal cord microvascular segments. Within 36~60 hours, the cell colonies gradually expanded and fused. After 72 hours, the cells spread across the base of the dish, forming a “cobblestone-like” monolayer. Immunocytochemical staining showed that more than 99% of the cells showed brown-red cytoplasm and were positive for factor Ⅷ-related antigen. It is these results that suggest this study has successfully established a convenient and stable primary rabbit spinal cord microvascular endothelial cells culture method.

Adhering to the educational tenet of "student-centered", we have integrated a micro-lecture on Reductive Tricarboxylic Acid Cycle into biochemistry to foster scientific research engagement and critical thinking skills of students—particularly those enrolled in the Outstanding and Foundation Strengthening programs. It supplements and deepens the content of the chapter Tricarboxylic Acid Cycle. In the micro-lecture we first summarize the characteristics of the oxidative tricarboxylic acid cycle, which releases wind (carbon dioxide) and fire (energy). The cycle is therefore considered as a windy and flaming wheel, a powerful Nimbus-like vehicle from a famous Chinese legendary. Students are then guided through a step-by-step analysis of the molecular basis of the reduced tricarboxylic acid cycle, which reverses the wheel to absorb wind and fire and complete carbon fixation, following the First Law of thermodynamics. Finally, the discovery of this cycle is traced and the scientific and social significance of this discovery is highlighted. This course has achieved good results in practical teaching applications. Therefore, we present the design ideas, innovative features, highlights, and implementation outcomes of this micro-lecture, inviting peer review and constructive feedback to facilitate collaborative refinement.

Genetics, which provides important theoretical knowledge for the cultivation of students majoring in biology, is a discipline that studies the law of biological heredity and variation. In the era of highly advanced information technology, the blended online and offline teaching model has progressively been integrated into university classrooms, which seamlessly merges offline teaching with "Internet +" and greatly improves the outcomes and effectiveness of student learning and teacher instruction. Taking the genetics course as a platform, this paper first examines the complementary features of online and offline teaching methods. Then, the genetic teaching model that was carried out through various online platforms and resources were designed and optimized from purely online instruction and blended online-offline instruction respectively. The assessment and evaluation methodologies were also enhanced. The findings of the investigation on the impact of teaching practices showed that a notable enhancement in students’ enthusiasm for learning genetic courses was achieved. This was reflected in the fact that an increasing number of students selected genetic-related topics in science and innovation competitions. Meanwhile, compared with the non-implementation of blended teaching reform, students’ academic performance in genetics courses has also been significantly improved, with a total score of about 5-6 points. The implementation of the innovative blended teaching model will further enhance the efficiency of classroom teaching innovation and talent training.