Various types of RNA within cells play crucial roles in regulating cellular biological processes.RNA modifications are chemical modifications on substrate RNA with chemical groups.8-hydrox-yguanosine modification of RNA can impact the stability,structure and function of RNA.This modifica-tion enhances the diversity of RNA functions and roles.During oxidative stress,8-hydroxyguanine is a common and signature form of RNA chemical oxidative modification in cells.Both the structure and func-tion of RNA may be affected by 8-hydroxyguanine modification.The 8-hydroxyguanine modification of RNA has been demonstrated to impact both the structure and function of RNA through the induction of RNA strand breaks and base shedding.Research suggests that the presence of 8-hydroxyguanine modifi-cation in RNA may serve as a potential biomarker for disease progression.As interests in RNA modifica-tions grow,the 8-hydroxyguanine modification of RNA has garnered increasing attention.This article mainly reviews the mechanisms involved in the generation of 8-hydroxyguanine modification in RNA,its biological implications,and the proteins involved in regulating and repairing this modification,the detec-tion technology for 8-hydroxyguanine modified RNA,and the relationship between 8-hydroxyguanine mod-ification of RNA and various diseases,including neuropathic diseases and cancer.The primary objective is to offer a deeper understanding of the biological significance of RNA modification and the potential in-volvement of 8-hydroxyguanine modified RNA in disease pathogenesis.

DNA damage triggers cells to initiate a series of DNA damage response(DDR),including DNA damage repair,cell cycle checkpoint activation,cell cycle arrest,activation of various intracellular signal transduction pathways,and cell apoptosis,etc.DNA Damage Repair,an important mechanism by which cells maintain genomic stability,was awarded the Nobel Prize in Chemistry in 2015.DNA damage repair pathways mainly include:base-excision repair(BER),nucleotide excision repair(NER),mis-match repair(MMR),homologous recombination(HR)and non-homologous end joining(NHEJ).They play an important role in the repair of DNA damage such as single-strand break(SSB)or double-strand break(DSB).DNA damage repair defects are closely related to tumorigenesis and development and is also an important target for tumor therapy.Poly-ADP-ribose polymerase(PARP)and breast canc-er susceptibility gene BRCA1/2 and others in the DNA damage repair pathways have synthetic lethality effects.It makes PARP inhibitor(PARPi)be the first and currently the only commercially available syn-thetic lethal target drug for tumor therapy.PARPi has good efficacy in the treatment of ovarian cancer and a variety of solid tumors,which make the research and development of synthetic lethal target drugs related to DNA damage repair and DDR pathway become a hot spot.Other targets under research mainly in-clude:ataxia telangiectasia-mutated protein(ATM),ataxia telangiectasia and RAD3 related protein(ATR),DNA-dependent protein kinase catalytic subunit(DNA-PKcs),checkpoint kinasel(CHK1),Checkpoint kinase 2(CHK2),mitogen-preventing protein kinase WEE 1,etc.The combination of PARPi with other DDR target drugs,anti-angiogenesis drugs or immune checkpoint inhibitors may be-come effective means and development prospect to overcome PARPi resistance and improve the therapeu-tic effect.Here we review the key molecules and potential tumor therapeutic targets in DNA damage re-pair and related DDR pathways,and the research on synthetic lethal targets and their application and prospect in ovarian cancer.We aim to provide guidance for basic research and clinical application.

The adipose tissue serves as the largest energy storage and endocrine organ in the body.It plays a crucial role in regulating energy homeostasis and hormone secretion.However,with aging,the adipose tissue undergoes significant changes that can have detrimental effects on overall health.One of the key features of aging adipose tissue is the presence of senescent cells.These cells touch neighboring cells through the secretion of cytokines and the release of metabolites.This interaction can disrupt the normal function of adipose tissues and lead to systemic chronic inflammation or metabolic disorders.Cur-rently,the microenvironment of the aging adipose tissue has not been fully clarified.Therefore,here we review the changes in the microenvironment of aging adipose tissues,including various cell types in the adipose tissue,fibrosis caused by extracellular matrix accumulation,cytokine and metabolites.These al-terations can lead to systemic chronic low-grade inflammation,insulin resistance,and premature aging.Finally,several strategies expected to delay adipose tissue aging are introduced,including improving adi-pocyte thermogenesis,senolytics,diet and exercise.This review aims to provide ta heoretical reference for the treatment of ageing-related diseases.

Antibiotic resistance is considered one of the most serious global threats to human health in the 21st century.The overuse of antibiotics has aggravated the development of bacterial resistance.Therefore,it is necessary to further study the mechanisms of bacterial resistance and explore new types of resistance and bacteriostatic strategies.This article provides an overview of the mechanisms of bacterial resistance and new antibacterial strategies for drug-resistant bacteria.It elaborates on the molecular mechanisms of three types of resistance:inherent resistance,acquired resistance and adaptive resistance.It also discusses new antibacterial strategies such as new antibacterial compound molecules,phage therapy,CRISPR-Cas system therapy and antisense therapy.This review aims to summarize the mechanisms of bacterial resistance and provide a reference for subsequent prevention and treatment of bacterial resistance.

Single base editors(BEs)are a new class of base editors derived from the CRISPR/Cas sys-tem or transcription activator-like effector(TALE)gene editing technology,which can accurately edit a single base without introducing DNA double-strand-breaks or donor DNA.Compared with the previous genome editing technologies,it has the advantages of less by-products,higher editing efficiency,and lar-ger base editing range,which can be used for the treatment of genetic anemia caused by point mutations.In this paper,the development of single base editing technology and its progress in gene therapy for trea-ting genetic anemia caused by gene mutations are summarized,which can provide a theoretical reference for the clinical trial of gene therapy for clinical anemia.

The loss of dopaminergic neurons in the substantia nigra compacta and the aggregation of α-synuclein are the hallmark symptoms of Parkinson's disease(PD),a prevalent neurodegenerative condi-tion.The pathological mechanisms of PD are very complex,and microglia activation-mediated neuroin-flammation has recently been found to be an important factor in dopaminergic neuronal loss in PD.Cur-rent pharmacological treatments can only alleviate the symptoms of dyskinesia but cannot slow down the pathological process.Exercise,as a non-pharmacological physical intervention,has been shown to be helpful in preventing and delaying the onset of neurodegenerative pathologies,and moderate exercise pro-duces some anti-inflammatory effects and reduces dopaminergic neuron loss.However,the regulatory mechanisms of exercise in ameliorating microglia-mediated neuroinflammation and preventing the patho-logical process of PD are not well understood.Some studies have found that exercise can ameliorate fac-tors associated with PD,such as abnormally aggregated α-synuclein,brain-derived neurotrophic factor levels,autophagy,and oxidative stress.Therefore,this paper describes the molecular mechanism of ex-ercise to improve microglia-mediated neuroinflammation in the prevention of Parkinson's disease from the above aspects and provides new therapeutic targets for the prevention and treatment of PD.

Endoplasmic reticulum stress(ERS)is a protective cellular response that occurs when cells face hypoxia or nutrient deprivation.It alleviates protein accumulation in the endoplasmic reticulum(ER)by the unfolded protein response.Unfolded or misfolded proteins that are not efficiently cleared by the unfolded protein response pathway are degraded by endoplasmic reticulum-phagy(ER-phagy),which is trigged by ERS to restore ER morphology.ER-phagy is mediated by ER-phagy receptors.In mammali-an and yeast cells,various ER-phagy receptors exist that promote ER fragment formation,capture autoph-agic cargos and deliver them to autolysosomes for degradation.Each ER-phagy receptor has unique struc-tural features that determine its mode of cargo capture.Additionally,ERS regulates ER-phagy by media-ting the expression and phosphorylation of ER-phagy receptors.Research has shown that ERS-induced ER-phagy plays a crucial role in the pathogenesis of various human diseases.Therefore,elucidating the specific mechanisms underlying ERS-induced ER-phagy provides a theoretical basis for the prevention and treatment of ER-phagy-related diseases.Herein,we review the molecular mechanisms of ERS-induced ER-phagy mediated by ER-phagy receptors in mammals(FAM134B,RTN3L,SEC62,CCPG1)and yeasts(Atg39,Atg40,Erp1),as well as the connection between ERS-induced ER-phagy and human diseases such as neurodegenerative disorders and cancer,aiming to provide new strategies for the preven-tion and treatment of ER-phagy-related diseases.

In recent years,studies have shown that C/EBP β plays an important role in the occurrence and development of liver cancer,but its specific molecular regulatory mechanism is still unclear.In this study,we analyzed the GEO database and the Kaplan-Meier Plotter database and found that the mRNA expression of C/EBP β was low in hepatocellular carcinoma(HCC)cells(P＜0.05),and its low ex-pression was closely related to the prognosis of HCC patients.Furthermore,functional enrichment analy-sis and TIMER database analysis showed that C/EBP β was mainly involved in biological processes such as cell cycle and DNA transcription,and the expression level of C/EBP β had a strong correlation with the immune infiltration of CD4+T cells and macrophages(P＜0.05).To further investigate the effect of C/EBP β on the proliferation and migration of HCC cells.In the experiment,HCC cells were transiently transfected with C/EBP β siRNA and divided into si-NC group and siC/EBP β group.The mRNA and protein levels of C/EBP β in HCC cells were significantly reduced by qRT-PCR and Western blot(P＜0.05),and MTT detection,plate cloning assay,and 5-ethynyl-2'deoxyuracil nucleoside(Edu)assay confirmed that knockdown of C/EBP β promotes the proliferation of HCC cells(P＜0.05);Transwell and scratch assays confirmed that knockdown of C/EBP β promote the migration of HCC cells;Western blot method was used to detect the effect of knockdown of C/EBP β on the expression of migration-related proteins(E-cadherin,N-cadherin)and Wnt/β-catenin signaling pathway proteins.The results showed that knockdown of C/EBP β promotes epithelial-mesenchymal transition(EMT)and activates gene ex-pression of Wnt/β-catenin signaling pathway in HCC cells(P＜0.05).In conclusion,C/EBP β was un-derexpressed in HCC tissues and was positively correlated with the survival prognosis of patients.Knock-down of C/EBP β may promote the proliferation,migration,and epithelial-mesenchymal transformation of HCC cells by activating the Wnt/β-catenin signaling pathway,which provides a basis for the role of C/EBP β in the occurrence and development of HCC and may be a potential target in the diagnosis and treatment of HCC.

The cdc73(cell division cycle 73)gene encodes the RNA polymerase Ⅱ cofactor Cdc73 in fis-sion yeast(Schizosaccharomyces Pombe),and is involved in G2 checkpoint activation and regulates the cell cycle.However,whether Cdc73 regulates cell mitotic dynamics is unknown.In this study,fluores-cent protein labeling and live cell imaging techniques were used to investigate the effects of cdc73 deletion on sexual reproduction and the dynamics of microtubules,actin,mitochondria,and histones during mito-sis.The results showed that in sexual reproduction,cdc73 deletion resulted in a 14.23％increase in the length of ascospores and a 64.08％decrease in the number of cells producing four spores.Analysis of the live cell imaging results revealed that,in mitosis,the elongation length of microtubules in anaphase was shortened by 11.21％,and the elongation time was reduced by 17.39％;the formation and contraction rates of actin rings decreased by 33.33％and 26.09％,respectively,and the formation and contraction times were prolonged by 58.00％and 40.38％,respectively.Meanwhile,the expression levels of actin ring,mitochondrion,and histones also increased.This study revealed the cdc73 deletion inhibits spindle elongation and delays actin ring formation and contraction in mitosis,which provides some scientific basis for further exploring the involvement of Cdc73 in regulating microtubule and actin dynamics in cell divi-sion.

Heterotypic cell-in-cell structures(heCICs)mediate unique non-autonomous cell death,which are widely involved in a variety of important pathological processes,such as tumorigenesis,pro-gression and clinical prognosis.Methylenetetrahydrofolata dehydrogenase 2(MTHFD2),one of the key enzymes of one-carbon metabolism,is highly expressed in a variety of tumor cells.In this study,in order to investigate the effect of MTHFD2 on the formation of heCICs,liver cancer cells and immune cells were first labeled separately by live cell dyes,and the heCIC model was established by using fluorescence mi-croscopy for cell imaging and analysis.After transiently knocking down MTHFD2 in cells by RNAi,we found that the ability of PLC/PRF/5 and Hep3B to form heCICs with immune cells was significantly in-creased(all P＜0.01).MTHFD2 recombinant expression plasmid was constructed by the homologous re-combination method,and MTHFD2 overexpression cell lines were further constructed.Then,the effect of MTHFD2 overexpression on the ability to form heCICs was detected by co-culturing the overexpression cell lines with immune cells.The results showed that the rate of heCIC formation was significantly re-duced after overexpression of MTHFD2(all P＜0.001).In conclusion,this study demonstrated that MTHFD2 is a negative regulator of heCIC formation,providing a research basis for targeting MTHFD2 to promote heCIC formation and enhance the in-cell killing of immune cells.