水热反应条件对SnO_(2)/Bi_(2)WO_(6)复合材料光催化活性的影响

本文以不同水热条件制备了正交晶系结构的两种二氧化锡和一种钨酸铋,并制备出了两种由纳米片组成的花状团簇的二氧化锡/钨酸铋复合光催化材料。通过X射线衍射仪、扫描电子显微镜、比表面积孔隙度测试仪、紫外可见分光光度计等手段对三种样品的样貌、比表面积、孔隙度、孔体积及吸光度测试表征。用碘钨灯来模拟太阳光,研究对比以不同水热条件下制备的钨酸铋以及两种二氧化锡/钨酸铋复合材料作催化剂催化降解罗丹明B的光催化性能。综合实验数据分析,发现二氧化锡/钨酸铋复合样品的衍射峰与钨酸铋样品的衍射峰一致,不同的水热条件会影响产物的物相结构,但对晶体结构和结晶度无影响。光催化360 min时,水热条件为180℃、12 h的钨酸铋对罗丹明B的降解率是33%、水热条件为180℃、6 h的二氧化锡和180℃、12 h的钨酸铋制备的复合物样品1对罗丹明B的降解率是46%、水热条件为180℃、12 h的二氧化锡和180℃、12 h的钨酸铋制备的复合物样品2对罗丹明B的降解率是57%。二氧化锡/钨酸铋复合样品的催化效果优于纯钨酸铋,同时也说明不同水热反应条件对复合光催化材料的催化性能有一定的影响。

金属二聚体和氮共掺杂石墨烯(Gra)M_(2)N_(6)-Gra(M=Cr-Cu)的NO_(2)吸附特性理论研究

NO_(2)是空气污染物的主要成分之一,设计和开发高效的气敏传感器对NO_(2)进行检测具有重要意义.本工作利用基于密度泛函理论(DFT)的第一性原理计算方法对不同过渡金属原子形成的金属二聚体和氮共掺杂石墨烯(Gra)M_(2)N_(6)-Gra(M=Cr-Cu)的NO_(2)吸附特性进行了研究.结果表明,NO_(2)分子与M_(2)N_(6)-Gra之间均存在明显的化学吸附作用.其中,Ni_(2)N_(6)-Gra和Cu_(2)N_(6)-Gra体系具备较为适中的恢复时间(分别约为5秒和14分钟),这意味着这两个体系是开发新型NO_(2)气敏材料的潜在候选者.其它体系(M_(2)N_(6)-Gra,M=Cr-Co)强的吸附作用导致恢复时间过长,从而使得它们不适合作为NO_(2)气敏材料.这一研究不仅有望为设计和开发性能优异的新型NO_(2)气敏材料提供有益理论指导,还将有益于人们深入认识M_(2)N_(6)-Gra材料的NO_(2)电催化合成NO或NH 3性能.

Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

Development and identification of two novel wheat-rye 6R derivative lines with adult-plant resistance to powdery mildew and high-yielding potential

Powdery mildew,caused by Blumeria graminis f.sp.tritici(Bgt),is a devastating disease that seriously threatens wheat yield and quality.To control this disease,host resistance is the most effective measure.Compared with the resistance genes from common wheat,alien resistance genes can better withstand infection of this highly variable pathogen.Development of elite alien germplasm resources with powdery mildew resistance and other key breeding traits is an attractive strategy in wheat breeding.In this study,three wheat-rye germplasm lines YT4-1,YT4-2,and YT4-3 were developed through hybridization between octoploid triticale and common wheat,out of which the lines YT4-1 and YT4-2 conferred adult-plant resistance(APR)to powdery mildew while the line YT4-3 was susceptible to powdery mildew during all of its growth stages.Using genomic in situ hybridization,multi-color fluorescence in situ hybridization,multi-color GISH,and molecular marker analysis,YT4-1,YT4-2,and YT4-3 were shown to be cytogenetically stable wheat-rye 6R addition and T1RS.1BL translocation line,6RL ditelosomic addition and T1RS.1BL translocation line,and T1RS.1BL translocation line,respectively.Compared with previously reported wheat-rye derivative lines carrying chromosome 6R,YT4-1 and YT4-2 showed stable APR without undesirable pleiotropic effects on agronomic traits.Therefore,these novel wheat-rye 6R derivative lines are expected to be promising bridge resources in wheat disease breeding.

Application of Echocardiography Combined with Blood SAA, IL-6, PCT, and CRP Detection in the Diagnosis and Treatment of Kawasaki Disease in Children

Objective: To understand the application of echocardiography combined with blood SAA, IL-6, PCT, and CRP detection in the diagnosis and treatment of Kawasaki disease in children. Methods: 56 children with Kawasaki disease were selected as the study subjects as the treatment group, and 54 children with other diseases during the same period were selected as the control group. Echocardiography, blood SAA, IL-6, PCT and CRP were detected before and after treatment to observe the results of the two groups. A database was established to compare the changes of various indicators between the two groups, as well as the application value of each indicator in the clinical diagnosis and treatment of Kawasaki disease, and the pros and cons of the application of each indicator in the diagnosis and treatment of children with Kawasaki disease were analyzed, so as to provide a clearer early warning mechanism for the clinical diagnosis and treatment of children with Kawasaki disease. Results: There was no significant difference in the results of related imaging indexes in the control group before and after treatment (P > 0.05). There was no significant difference in the results of relevant imaging indicators in the treatment group before and after treatment (P > 0.05), except for LMCA (P < 0.05). The comparison of imaging related indicators before and after treatment between the two groups showed that except for no statistically significant difference in LMCA and RMCA before treatment (P > 0.05), all other indicators had statistical significance (P < 0.05). The results of relevant laboratory indexes in control group before and after treatment were statistically significant (P < 0.05). The results of relevant laboratory indexes before and after treatment in the treatment group were statistically significant (P < 0.05). The results of relevant laboratory indicators were compared between the two groups, except for the results of SAA, IL-6 and PCT before treatment, which were not statistically significant (P > 0.05), the differences in all other indicators were statistically significant (P Conclusion: The combination of echocardiography with blood SAA, IL-6, PCT, and CRP detection can establish the optimal evaluation plan for accurate and effective diagnosis, treatment, and prognosis of Kawasaki disease in children, providing more accurate and reliable diagnostic and treatment methods and laboratory data for clinical practice, and thus providing strong protection for children’s health.

联合检测GR、NO、IL-6对儿童病毒性心肌炎的评价

目的联合几项免疫介导的血清学指标来提高对儿童儿童病毒性心肌炎(VMC)的诊断效率,为临床提供早期的诊断价值,避免漏检对患儿引起的不良结局。方法收集泗洪医院2018年1月至2022年6月在儿科住院就诊符合条件的45例VMC病例纳入VMC组,45例单纯病毒感染患儿纳入NVMC组以及体检的50名正常儿童纳入对照组。收集研究对象一般资料,包括白细胞介素6(IL-6)、谷胱甘肽还原酶(GR)、一氧化氮(NO)以及心肌酶谱、肌钙蛋白结果。用受试者工作特征(ROC)曲线各单项指标对VMC的价值分析,并采用Logistic回归模型构建模型来预判VMC。结果VMC组的肌酸激酶同工酶(CK-MB)、天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、肌钙蛋白I(cTnI)、NO、IL-6含量明显高于NVMC组和对照组,而GR含量则明显低于后两组;用各单项指标来对VMC进行ROC曲线分析,结果显示特异性最高的是cTnI的0.907,敏感性最高的是IL-6的0.912,AUC面积最大的是NO,为0.883;由cTnI、CK-MB、GR、NO、IL-6等5项指标联合建立的回归模型,当诊断界值定为0.55时,模型对VMC的AUC为0.976,敏感性为0.977,特异性为0.982,此时约登指数最大为0.959。结论用NO、GR、IL-6联合cTnI、CK-MB构建的回归模型对VMC的诊断特异性以及敏感性明显高于其他的单一指标。能够为临床医生及早的诊断儿童VMC提供有力的依据和辅助。

Large‑scale transcriptomic and genomic analyses reveal a novel functional gene SERPINB6 for chicken carcass traits

Background Carcass traits are crucial indicators of meat production efficiency.However,the molecular regulatory mechanisms associated with these traits remain unclear.Results In this study,we conducted comprehensive transcriptomic and genomic analyses on 399 Tiannong partridge chickens to identify key genes and variants associated with carcass traits and to elucidate the underlying regulatory mechanisms.Based on association analyses with the elastic net(EN)model,we identified 12 candidate genes(AMY1A,AP3B2,CEBPG,EEF2,EIF4EBP1,FGFR1,FOXD3,GOLM1,LOC107052698,PABPC1,SERPINB6 and TBC1D16)for 4 carcass-related traits,namely live weight,dressed weight,eviscerated weight,and breast muscle weight.SERPINB6 was identified as the only overlapping gene by 3 analyses,EN model analysis,weighted gene co-expression network analysis and differential expression analysis.Cell-level experiments confirmed that SERPINB6 promotes the proliferation of chicken DF1 cells and primary myoblasts.Further expression genome-wide association study and association analysis indicated that rs317934171 is the critical site that enhances SERPINB6 expression.Furthermore,a dual-luciferase reporter assay proved that gga-miR-1615 targets the 3′UTR of SERPINB6.Conclusions Collectively,our findings reveal that SERPINB6 serves as a novel gene for chicken carcass traits by promoting fibroblast and myoblast proliferation.Additionally,the downstream variant rs317934171 regulates SERPINB6 expression.These results identify a new target gene and molecular marker for the molecular mechanisms of chicken carcass traits.

Learning Sequential and Structural Dependencies Between Nucleotides for RNA N6-Methyladenosine Site Identification

N6-methyladenosine(m6A)is an important RNA methylation modification involved in regulating diverse biological processes across multiple species.Hence,the identification of m6A modification sites provides valuable insight into the biological mechanisms of complex diseases at the post-transcriptional level.Although a variety of identification algorithms have been proposed recently,most of them capture the features of m6A modification sites by focusing on the sequential dependencies of nucleotides at different positions in RNA sequences,while ignoring the structural dependencies of nucleotides in their threedimensional structures.To overcome this issue,we propose a cross-species end-to-end deep learning model,namely CR-NSSD,which conduct a cross-domain representation learning process integrating nucleotide structural and sequential dependencies for RNA m6A site identification.Specifically,CR-NSSD first obtains the pre-coded representations of RNA sequences by incorporating the position information into single-nucleotide states with chaos game representation theory.It then constructs a crossdomain reconstruction encoder to learn the sequential and structural dependencies between nucleotides.By minimizing the reconstruction and binary cross-entropy losses,CR-NSSD is trained to complete the task of m6A site identification.Extensive experiments have demonstrated the promising performance of CR-NSSD by comparing it with several state-of-the-art m6A identification algorithms.Moreover,the results of cross-species prediction indicate that the integration of sequential and structural dependencies allows CR-NSSD to capture general features of m6A modification sites among different species,thus improving the accuracy of cross-species identification.

Analysis of Phenotypes Associated with Deficiency of PAX6 Haplotypes in Chinese Aniridia Families

Objective To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency.Methods A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives.The clinical feature analysis included the evaluation of visual acuity,intraocular pressure,slit-lamp anterior segment examination,fundus photography,and spectral domain optical coherence tomography.To identify the mutation responsible for aniridia,targeted next-generation sequencing was used as a beneficial technique.Results A total of 4 mutations were identified,consisting of two novel frameshift mutations(c.314delA,p.K105Sfs*33 and c.838_845dup AACACACC,p.S283Tfs*85),along with two recurring nonsense mutations(c.307C>T,p.R103X and c.619A>T,p.K207*).Complete iris absence,macular foveal hypoplasia,and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families,while corneal lesions,cataracts,and glaucoma exhibited heterogeneity both among the families and within the same family.Conclusion In our study,two novel PAX6 mutations associated with aniridia were identified in Chinese families,which expanded the phenotypic and genotypic spectrum of PAX6 mutations.We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families.

Long non-coding RNA GATA6-AS1 is mediated by N6-methyladenosine methylation and inhibits the proliferation and metastasis of gastric cancer

BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.

Imprinting at the KBTBD6 locus involves species-specific m ternal methylation and monoallelic expression in livestock animals

Background The primary differentially methylated regions(DMRs) which are maternally hypermethylated serve as imprinting control regions(ICRs) that drive monoallelic gene expression, and these ICRs have been investigated due to their implications in mammalian development. Although a subset of genes has been identified as imprinted, in-depth comparative approach needs to be developed for identification of species-specific imprinted genes. Here, we examined DNA methylation status and allelic expression at the KBTBD6 locus across species and tissues and explored potential mechanisms of imprinting.Results Using whole-genome bisulfite sequencing and RNA-sequencing on parthenogenetic and normal porcine embryos, we identified a maternally hypermethylated DMR between the embryos at the KBTBD6 promoter Cp G island and paternal monoallelic expression of KBTBD6. Also, in analyzed domesticated mammals but not in humans, non-human primates and mice, the KBTBD6 promoter Cp G islands were methylated in oocytes and/or allelically methyl-ated in tissues, and monoallelic KBTBD6 expression was observed, indicating livestock-specific imprinting. Further analysis revealed that these Cp G islands were embedded within transcripts in porcine and bovine oocytes which coexisted with an active transcription mark and DNA methylation, implying the presence of transcription-dependent imprinting.Conclusions In this study, our comparative approach revealed an imprinted expression of the KBTBD6 gene in domesticated mammals, but not in humans, non-human primates, and mice which implicates species-specific evolution of genomic imprinting.

New insights into developmental biology of Eimeria tenella revealed by comparative analysis of mRNA N6-methyladenosine modification between unsporulated oocysts and sporulated oocysts

Evidence showed that N6-methyladenosine(m^(6)A)modification plays a pivotal role in influencing RNA fate and is strongly associated with cell growth and developmental processes in many species.However,no information regarding m^(6)A modification in Eimeria tenella is currently available.In the present study,we surveyed the transcriptome-wide prevalence of m^(6)A in sporulated oocysts and unsporulated oocysts of E.tenella.Methylated RNA immunoprecipitation sequencing(MeRIP-seq)analysis showed that m^(6)A modification was most abundant in the coding sequences,followed by stop codon.There were 3,903 hypermethylated and 3,178 hypomethylated mRNAs in sporulated oocysts compared with unsporulated oocysts.Further joint analysis suggested that m^(6)A modification of the majority of genes was positively correlated with mRNA expression.The mRNA relative expression and m^(6)A level of the selected genes were confirmed by quantitative reverse transcription PCR(RT-qPCR)and MeRIP-qPCR.GO and KEGG analysis indicated that differentially m^(6)A methylated genes(DMMGs)with significant differences in mRNA expression were closely related to processes such as regulation of gene expression,epigenetic,microtubule,autophagy-other and TOR signaling.Moreover,a total of 96 DMMGs without significant differences in mRNA expression showed significant differences at protein level.GO and pathway enrichment analysis of the 96 genes showed that RNA methylation may be involved in cell biosynthesis and metabolism of E.tenella.We firstly present a map of RNA m^(6)A modification in E.tenella,which provides significant insights into developmental biology of E.tenella.

ALKBH5 suppresses autophagic flux via N6-methyladenosine demethylation of ZKSCAN3 mRNA in acute pancreatitis

BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancreatitis(AP).AIM To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP.METHODS The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells(MPC-83),and the results were confirmed by the levels of amylase and inflammatory factors.Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes.ZKSCAN3 and ALKBH5 were knocked down to study the function in AP.A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH.RESULTS The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established.The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP.The expression of ZKSCAN3 was upregulated in AP.Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors,LC3-II/I and SQSTM1.Furthermore,ALKBH5 was upregulated in AP.Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP.Notably,the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA.The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP.Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA,which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner.CONCLUSION ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP,thereby aggravating the severity of the disease.

Identification of marker genes associated with N6-methyladenosine and autophagy in ulcerative colitis

BACKGROUND Both N6-methyladenosine(m6A)methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis(UC).However,a systematic exploration of the role of the com-bination of m6A methylation and autophagy in UC remains to be performed.AIM To elucidate the autophagy-related genes of m6A with a diagnostic value for UC.METHODS The correlation between m6A-related genes and autophagy-related genes(ARGs)was analyzed.Finally,gene set enrichment analysis(GSEA)was performed on the characteristic genes.Additionally,the expression levels of four characteristic genes were verified in dextran sulfate sodium(DSS)-induced colitis in mice.RESULTS GSEA indicated that BAG3,P4HB and TP53INP2 were involved in the inflammatory response and TNF-αsignalling via nuclear factor kappa-B.Furthermore,polymerase chain reaction results showed significantly higher mRNA levels of BAG3 and P4HB and lower mRNA levels of FMR1 and TP53INP2 in the DSS group compared to the control group.CONCLUSION This study identified four m6A-ARGs that predict the occurrence of UC,thus providing a scientific reference for further studies on the pathogenesis of UC.

Excitonic optical properties in monolayer SnP_(2)S_(6)

Quantum confinement effect and reduced dielectric screening in two-dimensional(2D)dramatically enhance theelectron-hole interactions.In this work,we use many-body perturbation theory and Bethe-Salpeter equation(BSE)toinvestigate the electronic and excitonic optical properties of monolayer SnP_(2)S_(6).Our findings reveal that the excitoniceffect dominates the optical absorption spectra in the visible light range,and the lowest-energy exciton X0 in monolayerSnP_(2)S_(6)is optically bright with the binding energy of 0.87 eV and the radiative lifetime of~10^(-11)s,which is highly advantageousto the photo-luminescence.Most importantly,the absence of optically forbidden states below the bright statesX0 would give rise to a high quantum efficiency of 2D SnP_(2)S_(6).We also find that applied biaxial strain can further shortenthe radiative lifetime of the bright states.These results imply that 2D SnP_(2)S_(6)is a promising candidate for the optoelectronicdevices.

Advances of N6-methyladenosine modification on circular RNA in hepatocellular carcinoma

N6-methyladenosine(m6A)is a reversible epigenetic modification, which is one of the most abundant modifiers in eukaryotic cells and has been commonly reported in messenger RNAs and non-coding RNAs. The processing modification of m6A regulates RNA transcription, processing, splicing, degradation, and translation, and plays an important role in the biological process of tumors. Circular RNA, which lacks the 5' cap structure, has been mistakenly regarded as a "junk sequence" generated by accidental shearing during the transcription process. However, it has been found that circRNAs can be involved in tumor invasion and metastasis through microRNAs, binding proteins, translated peptides, and m6A modifications. In this paper, we reviewed the role of m6A modifications in circRNA regulation and their functions in hepatocellular carcinoma and discussed their potential clinical applications and future development in this field.

Knockout of C6orf120 in Rats Alleviates Concanavalin A-induced Autoimmune Hepatitis by Regulating Macrophage Polarization

Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors.Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68^(+)CD86^(+)M1 macrophages from the liver and spleen in the C6orf120^(-/-)rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68^(+)CD80^(+)M1 macrophages and inhibited the CD68^(+)CD206^(+)M2 phenotype.Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120^(-/-)rats.

Modulation of host N6-methyladenosine modification by gut microbiota in colorectal cancer

As a research hotspot in the field of molecular biology,N6-methyladenosine(m6A)modification has made progress in the treatment of colorectal cancer(CRC),leukemia and other cancers.Numerous studies have demonstrated that the tumour microenvironment(TME)regulates the level of m6A modification in the host and activates a series of complex epigenetic signalling pathways through interactions with CRC cells,thus affecting the progression and prognosis of CRC.However,with the diversity in the composition of TME factors,this action is reci-procal and complex.Encouragingly,some studies have experimentally revealed that the intestinal flora can alter CRC cell proliferation by directly acting on m6A and thereby altering CRC cell proliferation.This review summarizes the data,supporting the idea that the intestinal flora can influence host m6A levels through pathways such as methyl donor metabolism and thus affect the progression of CRC.We also review the role of m6A modification in the diagnosis,treatment,and prognostic assessment of CRC and discuss the current status,limitations,and potential clinical value of m6A modification in this field.We propose that additional in-depth research on m6A alterations in CRC patients and their TME-related targeted therapeutic issues will lead to better therapeutic outcomes for CRC patients.

Study on the expression and prognostic relationship of MYL6B in liver cancer based on bioinformatics

BACKGROUND Primary liver cancer is a prevalent and deadly cancer type.Despite treatment advances,prognosis remains poor,with high recurrence rates.Early detection is crucial but challenging due to the disease’s insidious nature.Myosin proteins play significant roles in cancer development,influencing cell migration,invasion,and tumor suppression.MYL6B,a myosin light chain,is involved in various cellular processes and has been associated with poor prognosis in colorectal adenocarcinoma and potential as a biomarker in breast cancer.AIM To investigate the expression of MYL6B in liver hepatocellular carcinoma(LIHC)and its impact on prognosis and potential mechanisms of action using bioinformatics methods.METHODS The expression of MYL6B in pan-cancer and normal tissues was analyzed using the gene expression profiling interactive analysis 2 and tumor immune estimation resource databases.The expression level of MYL6B in LIHC tissues and its relationship with prognosis were analyzed,immunohistochemical analysis of MYL6B and its effect on immune cell infiltration,and the protein network were further studied.RESULTS MYL6B was highly expressed in diffuse large b-cell lymphoma,LIHC,pancreatic adenocarcinoma,skin cutaneous melanoma,thymoma,uterine corpus endometrial carcinoma,uterine carcinosarcoma,and lowly expressed in kidney chromophobe,acute myeloid leukemia,testicular germ cell tumors.The expression level of MYL6B was significantly different between cancer and normal tissues.It had a significant impact on both overall survival and disease-free survival.MYL6B is highly expressed in hepatocellular carcinoma and its expression level increases with cancer progression.High MYL6B expression is associated with poor prognosis in terms of overall survival and recurrence-free survival.The immunohistochemical level of MYL6B is high in hepatocellular carcinoma tissues,and MYL6B has a high level of immune infiltration inflammation.In protein network analysis,MYL6B is correlated with MYL2,MYL6,MYL9,MYLK4,MYLK2,MYL12A,MYL12B,MYH11,MYH9 and MYH10.CONCLUSION The expression level of MYL6B in LIHC was significantly higher than in normal liver tissues,and it was correlated with the degree of differentiation survival rate,and immune infiltration.MYL6B is a potential target for LIHC treatment.

LA-D-B1,a novel Abemaciclib derivative,exerts anti-breast cancer effects through CDK4/6

Background:Regulatory proteins involved in human cellular division and proliferation,cyclin-dependent kinases 4 and 6(CDK4/6)are overexpressed in numerous cancers,including triple-negative breast cancer(TNBC).TNBC is a common pathological subtype of breast cancer that is prone to recurrence and metastasis,and has a single treatment method.As one of the CDK4/6 inhibitors,abemaciclib can effectively inhibit the growth of breast tumors.In this study,we synthesized LA-D-B1,a derivative of Abemaciclib,and investigated its anti-tumor effects in breast cancer.Methods:Cellular viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Cell cloning and migration abilities were determined by colony formation assay and wound healing assay.Cell invasion abilities and adhesion were determined by cell invasion assay and cell adhesion assay.The impact of compound LA-D-B1 on cell proliferation and the cell cycle was analyzed through Western blotting,which quantified the levels of proteins associated with the cyclin-dependent kinase(CDK)4/6-cyclin D-Rb-E2F pathway.The in vivo anti-tumor activity of compound LA-D-B1 was investigated using a chick chorioallantoic membrane(CAM)model.Results:The study demonstrated that LA-D-B1 effectively suppressed breast cancer cell proliferation,induced apoptosis,and caused cell cycle arrest.Furthermore,LA-D-B1 reduced the expression of key proteins in the CDK4/6-cyclin D-Rb-E2F pathway,including CDK4,CDK6 and E2F1.The results also indicated significant antitumor activity of LA-D-B1 in a transplanted tumor model.Conclusion:In this study,LA-D-B1 demonstrated a potent anti-tumor effect by effectively suppressing cell proliferation and inhibiting cell cycle progression in breast cancer.These findings highlight the potential of LA-D-B1 as a valuable compound for enhancing therapeutic outcomes and controlling the progression of breast cancer.