[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective To investigate the role and mechanism of suramin(Sur)in acetaminophen(APAP)-induced acute liver injury in mice.Methods 8-10 weeks old C57BL/6J mice were randomly divided into the APAP group and APAP+Sur group(20 mg/kg suramin was injected 1 h before).After 18 hrs of fasting,400 mg/kg APAP was injected intraperitoneally to establish a mouse model of acute liver failure and the survival rate was recorded.An acute liver injury model of mice was established via intraperitoneal injection of 300 mg/kg APAP(other conditions remained unchanged).A control group was also established,with liver tissues and serum collected at 0,2,and 12 hours post-APAP treatment.ELISA and CBA techniques were adopted to detect the release of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum and the secretion of inflammatory factors.H&E staining and immunohistochemistry were used to detect liver tissue necrosis and inflammatory cell infiltration.DCFA-DH and ELISA techniques were used to detect the levels of reactive oxygen species(ROS),malondialdehyde(MDA)and glutathione(GSH)in liver tissues.Western blotting was employed to assess the activation of the JNK signaling pathway in liver tissues.Results Suramin treatment improved the survival rate of APAP-induced mice,reduced the release of transaminases and inflammatory factors in serum,and alleviated APAP-induced liver cell necrosis and inflammatory cell infiltration in the liver.Suramin treatment delayed APAP-induced GSH depletion in the liver,reduced MDA and ROS levels,and inhibited JNK pathway activation.Conclusion This study has confirmed the protective effect of suramin against acetaminophen-induced acute liver injury in mice.The mechanism is potentially related to oxidative stress and inflammation.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90％females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95％CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95％CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95％CI:0.004-0.076).The TyG index was 0.079(95％CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.

Objective:To delve into the intricate relationship between common genetic variations across the entire genome and the risk of non-syndromic cleft lip with or without cleft palate(NSCL/P).Methods:Utilizing summary statistics data from genome-wide association studies(GW AS),a thorough investigation to evaluate the impact of common variations on the genome were undertook.This involved assessing single nucleotide polymorphism(SNP)heritability across the entire genome,as well as within specific genomic regions.To ensure the robustness of our analysis,stringent quality control measures were applied to the GWAS summary statistics data.Criteria for inclusion encompassed the absence of missing values,a minor allele frequency≥1％,P-values falling within the range of 0 to 1,and clear SNP strand orientation.SNP meeting these stringent criteria were then meticulously included in our analy-sis.The SNP heritability of NSCL/P was calculated using linkage disequilibrium score regression.Addi-tionally,hierarchical linkage disequilibrium score regression to partition SNP heritability within coding re-gions,promoters,introns,enhancers,and super enhancers were employed,and the enrichment levels within different genomic regions using LDSC(v1.0.1)software were further elucidated.Results:Our study drew upon GWAS summary statistics data obtained from 806 NSCL/P trios,comprising a total of 2 418 individuals from the Chinese population.Following rigorous quality control procedures,490 593 out of 492 993 SNP were deemed suitable for inclusion in SNP heritability calculations.The observed SNP heritability of NSCL/P was 0.55(95％CI:0.28-0.82).Adjusting for the elevated disease pre-valence within our sample,the SNP heritability scaled down to 0.37(95％CI:0.19-0.55)based on the prevalence observed in the general Chinese population.Notably,our enrichment analysis unveiled significant enrichment of SNP heritability within enhancer regions(15.70,P=0.04)and super enhan-cer regions(3.18,P=0.03).Conclusion:Our study sheds light on the intricate interplay between common genetic variations and the risk of NSCL/P in the Chinese population.By elucidating the SNP heritability landscape across different genomic regions,we contribute valuable insights into the genetic basis of NSCL/P.The significant enrichment of SNP heritability within enhancer and super enhancer re-gions underscores the potential role of these regulatory elements in shaping the genetic susceptibility to NSCL/P.This paves the way for further research aimed at uncovering novel genetic pathogenic factors un-derlying NSCL/P pathogenesis.

Objective:To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies.Methods:We identified strong,independent single nucleotide polymorphisms(SNPs)of insomnia from the most up to date genome wide association studies(GWAS)within European ancestors and applied them as instrumental variable to GWAS of type 2 diabetes mellitus.After excluding SNPs that were significantly associated with smoking,physical activity,alcohol consumption,educational attainment,obesity,or type 2 diabetes mellitus,we assessed the impact of insomnia on type 2 diabetes mellitus using inverse variance weighting(IVW)method.Weighted median and MR-Egger regression analysis were also conducted to test the robustness of the association.We calculated the F statistic of the selected SNPs to test the applicability of instrumental variable and F statistic over than ten indicated that there was little possibility of bias of weak instrumental variables.We further examined the existence of pleiotropy by testing whether the intercept term in MR-Egger regression was significantly different from ze-ro.In addition,the leave-one-out method was used for sensitivity analysis to verify the stability and relia-bility of the results.Results:We selected 248 SNPs independently associated with insomnia at the genome-wide level(P＜5 ×10-8)as a preliminary candidate set of instrumental variables.After clum-ping based on the reference panel from 1000 Genome Project and removing the potential pleiotropic SNPs,a total of 167 SNPs associated with insomnia were included as final instrumental variables.The F statistic of this study was 39.74,which was in line with the relevance assumption of Mendelian randomi-zation.IVW method showed insomnia was associated with higher risk of type 2 diabetes mellitus that po-pulation with insomnia were 1.14 times more likely to develop type 2 diabetes mellitus than those without insomnia(95％CI:1.09-1.21,P＜0.001).The weighted median estimator(WME)method and MR-Egger regression showed similar causal effect of insomnia on type 2 diabetes mellitus.And MR-Egger re-gression also showed that the effect was less likely to be triggered by pleiotropy.Sensitivity analyses pro-duced directionally similar estimates.Conclusion:Insomnia is a risk factor of type 2 diabetes mellitus,which has positively effects on type 2 diabetes mellitus.Our study provides further rationale for indivi-duals at risk for diabetes to keep healthy lifestyle.

Purpose To investigate the expression of pro-tein of relevant evolutionary and lymphoid interest domain-con-taining 1(PRELID1)in gastric cancer tissues and to analyze its effect on prognosis,and the mechanism of influencing the prolif-eration and invasion ability of gastric cancer cells.Methods Using TCGA data and clinical data of 111 patients with gastric cancer,we analyzed the relationship between the expression of PRELID1 and clinicopathological parameters and the impact on clinical prognosis.The biological function of PRELID1 was pre-dicted by bioinformatics,and further verified by in vitro and in vivo experiments.Lentivirus was applied to regulate the level of PRELID 1 in gastric cancer cell line(MGC803)in vitro,and its effect on the proliferation,migration,and invasion of gastric cancer cells was observed.The nude mouse subcutaneous tumor-igenesis was used to observe the effect of PRELID1 on the growth of gastric cancer tissue in vivo.Results The expression of PRELID1 was significantly higher in gastric cancer tissues than that in the adjacent tissues(P＜0.001)and was positively cor-related with the cell proliferation indicator Ki67(P＜0.001).Cox regression model analysis showed that the high expression of PRELID 1 was an independent risk factor affecting the 5-year survival rate after radical gastrectomy(HR=2.336;95％CI=1.354-4.029).Gene enrichment results showed that the func-tion of PRELID1 was related to proliferation and JAK/STAT sig-naling.CCK-8 and Transwell experiments found that up-regula-tion of PRELID1 promoted the proliferation(P=0.016),mi-gration(P=0.016)and invasion(P=0.025)of gastric cancer cells,while down-regulation inhibited the proliferation(P=0.026),migration(P=0.048)and invasion(P=0.029).Subcutaneous tumor formation experiments in nude mice found that up-regulation of PRELID1 promoted the growth of gastric cancer tissue(P=0.047),while down-regulation was the oppo-site(P=0.005).Western blot detecting gastric cancer cells and gastric cancer tissues found that up-regulation of PRELID1 promoted the expression of JAK and STAT proteins(all P＜0.05),while down-regulation inhibited them(all P＜0.05).Conclusion The high expression of PRELID1 associated with poor prognosis may regulate the proliferation,migration and in-vasion of gastric cancer cells by up-regulating JAK/STAT signa-ling in gastric cancer.

OBJECTIVE To systematically evaluate the efficacy and safety of novel oral anticoagulants （NOAC） in the treatment of cancer-related venous thromboembolism （VTE） patients. METHODS Retrieved from PubMed， Cochrane Library， Embase， Web of Science， CNKI， and Wanfang database from the establishment of each database to August， 2023， randomized controlled trials （RCTs） about the efficacy of low-molecular-weight heparin （LMWH， control group） versus NOAC （trial group） in the treatment of cancer-related VTE patients were collected. After extracting the data from included clinical studies， meta-analysis was performed by using RevMan 5.0 statistical software. RESULTS A total of 7 RCTs were included， with a total of 3 790 patients. Compared with the control group， the recurrence rate of VTE in the trial group was significantly reduced （RR＝0.65， 95%CI 0.51-0.82， P＝0.000 4）， while the incidence of major bleeding was slightly higher than in the control group， but the difference was not statistically significant （RR＝1.13， 95%CI 0.83-1.53， P＝0.45）. The incidence of clinically relevant non-major bleeding （RR＝1.69， 95%CI 1.34-2.13， P＜0.000 01） and gastrointestinal bleeding （RR＝1.96， 95%CI 1.15-3.34， P＝0.01） in the trial group was significantly higher than in the control group. There was no statistically significant difference in the incidence of intracranial hemorrhage， all-cause mortality， and fatal pulmonary embolism between 2 groups （P＞0.05）. CONCLUSIONS For cancer-related VTE patients， NOAC is superior to LMWH in preventing venous thrombosis recurrence， and is not inferior to LMWH in terms of major bleeding， intracranial hemorrhage， all-cause mortality， and fatal pulmonary embolism.

Objective:To assess the association between short-term ambient air pollution exposure and arterial stiffness and whether obesity modifies these associations.Methods:A cross-sectional study was conducted based on Fangshan family cohort in Beijing. The 24 hours average air pollutant levels on the day cohort participants took baseline survey were calculated as short-term air pollution. A generalized additive model (GAM) with Gaussian links was used to estimate changes in typical carotid artery intima-media thickness (CIMT), brachial-ankle pulse wave velocity (BAPWV), pulse pressure (PP) and ankle-branchial index (ABI) after short-term exposure to each air pollution (PM 2.5, PM 10, SO 2, NO 2, CO). The cross-product terms of each air pollution, body mass index (BMI), and waist-to-hip ratio were included in the GAM model to test the interaction. Further, they conducted a stratified analysis to test their effects on the relationship between short-term exposure to each air pollution and the arterial stiffness indicators. Results:A total of 4 211 individuals were included in the analysis. Individuals' age was (58.9±8.7) years, of which 2 268 (53.9%) were female. Several covariates, including sociodemographic factors, lifestyle behaviors, and history of drugs, were included in the analysis. The results of the GAM analysis showed that an increase in PM 2.5 ( β=2.912×10 -4, 95% CI: 1.424×10 -4-4.400×10 -4, P<0.001), CO ( β=0.027, 95% CI: 0.011-0.043, P<0.001), SO 2 ( β=2.070×10 -3, 95% CI: 7.060×10 -4-3.430×10 -3, P=0.003), and NO 2 ( β=3.650×10 -4, 95% CI: 2.340×10 -5-7.060×10 -4, P=0.036) were associated with an increase in CIMT, while an increase in PM 10 ( β=0.018, 95% CI: 0.002-0.033, P=0.028) was associated with an increase in PP in the study population. Besides, the waist-to-hip ratio had an effect-modification on the correlation of short-term exposure of PM 2.5 (interaction P=0.015), NO 2 (interaction P=0.008), and CO (interaction P=0.044) with CIMT, and the correlation between short-term exposure of PM 2.5 (interaction P=0.002), NO 2 (interaction P=0.010), CO (interaction P=0.029), PM 10 (interaction P<0.001) with PP. The significant association between CIMT, PP, and air pollution concentrations was more visible in people with lower waist-to-hip ratios. Conclusions:Short-term ambient air pollution exposure was associated with arterial stiffness indicators, and there was an effect modification of waist-to-hip ratio on these associations, and lower waist-to-hip ratios may enhance the association between air pollution exposure and indicators.