Neural tube defects(NTDs)are a category of severe congenital birth defects that seriously af-fect 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 wide-spread application of proteomics has revealed the key role of histone modifications in epigenetic regula-tion,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 ge-nomic stability during neural tube closure,participating in the occurrence and development of NTDs.Ab-normal 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 de-velopment,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 di-rection.With the aim of revealing the key regulatory function of histone modifications in neural tube de-velopment,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 reg-ulates 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-ki-nase/Protein Kinase B(PI3K/AKT),particularly in the context of cancer.TRIM37 enhances the prolif-eration,metastasis,and invasion of tumor cells,including those in gallbladder cancer,renal cell carci-noma,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 proces-ses.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 fam-ily,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 with-in the nucleus,LSD 1 influences various biological processes in tumors,including proliferation,invasion,and metastasis.Previous studies have demonstrated that LSD1 is significantly overexpressed in gynecolog-ical 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 tran-sition(EMT)process.Furthermore,LSD1 inhibitors have shown promising therapeutic potential in ani-mal studies,particularly in restoring the sensitivity of ovarian cancer cells to platinum-based chemothera-py.This review summarizes the molecular mechanisms,functional targets,and associated signaling path-ways 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.

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 under-lying lactylation remain largely unclear,particularly regarding the enzymes responsible for adding"writ-ers",removing"erasers",and recognizing"readers"lactyl groups.This review systematically summari-zes 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 find-ings,this article aims to provide a theoretical basis for understanding the biological significance of lactyla-tion 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 expres-sion 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 immu-nity 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 exist-ing 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-oc-tamer 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 par-ticipates in coatomer complex Ⅰ(COP Ⅰ)-mediated retrograde transport,coatomer complex Ⅱ(COP Ⅱ)-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 com-plete 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 fu-sion 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 com-plex in several species,and summarize the factors that have synergetic effects with the COG complex in vesicle transport.

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 regula-tion,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,car-diomyocytes,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 mitochon-drial dysfunction in Hepa 1-6 cells,the synthesis and secretion of pancreatic β-cells and amyotrophic lat-eral sclerosis.In addition,MAM also affects cellular transcription processes by regulating calcium trans-port,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 treat-ment,in which the directional homing of T cells to tumor tissues is the core of the anti-tumor immune re-sponse,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 bar-riers,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 technolo-gy.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 a-doptive 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 puri-fied 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 doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,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 char-acterized by high malignancy and poor prognosis,warranting in-depth investigation.In recent years,mi-croRNAs(miRNAs)have emerged as crucial post-transcriptional regulators playing pivotal roles in tu-morigenesis and progression.Building upon this background,the present study specifically focuses on in-vestigating miR-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 prolif-eration 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 deter-mine the effect of miR-3910 on cell cycle progression,revealing accelerated cell cycle progression,a re-duced proportion of G0/G,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.