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 This study aimed to explore the relationships between residential greenness and cardiometabolic risk factors among rural adults in Xinjiang Uygur Autonomous Region(Xinjiang)and thus provide a theoretical basis and data support for improving the health of residents in this region. Methods We recruited 9,723 adult rural residents from the 51st Regiment of the Third Division of the Xinjiang Production and Construction Corps in September 2016.The normalized difference vegetation index(NDVI)was used to estimate residential greenness.The generalized linear mixed model(GLMM)was used to examine the association between residential greenness and cardiometabolic risk factors. Results Higher residential greenness was associated with lower cardiometabolic risk factor prevalence.After adjustments were made for age,sex,education,and marital status,for each interquartile range(IQR)increase of NDVI500-m,the risk of hypertension was reduced by 10.3%(OR=0.897,95%CI=0.836-0.962),the risk of obesity by 20.5%(OR=0.795,95%CI=0.695-0.910),the risk of type 2 diabetes by 15.1%(OR=0.849,95%CI=0.740-0.974),and the risk of dyslipidemia by 10.5%(OR=0.895,95%CI=0.825-0.971).Risk factor aggregation was reduced by 20.4%(OR=0.796,95%CI=0.716-0.885)for the same.Stratified analysis showed that NDVI500-m was associated more strongly with hypertension,dyslipidemia,and risk factor aggregation among male participants.The association of NDVI500-m with type 2 diabetes was stronger among participants with a higher education level.PM10 and physical activity mediated 1.9%-9.2%of the associations between NDVI500-m and obesity,dyslipidemia,and risk factor aggregation. Conclusion Higher residential greenness has a protective effect against cardiometabolic risk factors among rural residents in Xinjiang.Increasing the area of green space around residences is an effective measure to reduce the burden of cardiometabolic-related diseases among rural residents in Xinjiang.

Objective:To investigate the incidence characteristics and influencing factors of non-alcoholic fatty liver disease (NAFLD) in rural Uyghur ethnic group residents in Xinjiang Production and Construction Corps and to provide scientific evidence for early identification and prevention of NAFLD for residents.Methods:A total of 10 158 participants were included from the Xinjiang Uygur ethnic group population cohort. A prospective cohort study and Cox proportional hazards regression model analysis were used to explore the influencing factors and clustering of NAFLD, and the dose-response relationship between related biochemical indicators and the risk of NAFLD was studied using a restricted cubic spline.Results:The cumulative incidence rate of NAFLD was 6.9%, and the incidence density of NAFLD was 12.06/1 000 person-years. The incidence density of NAFLD in females was higher than in males (14.72/1 000 person-years vs. 9.17/1 000 person-years, P<0.001). The incidence density of NAFLD gradually increased with age in the total population, both men and women (all P<0.001). In the general population, an education level of junior high school or above was a protective factor for NAFLD, while older age, divorce, widowhood, overweight, obesity, hypertension, increased glomerular filtration rate, decreased HDL-C, increased LDL-C, and increased ALT were risk factors for NAFLD. Estimated glomerular filtration rate (eGFR), HDL-C, LDL-C, and ALT were non-linearly correlated with the incidence of NAFLD, and there was a significant dose-response relationship between them. Only 19.1% of residents had no NAFLD risk factors; over 80.9% had ≥1 NAFLD risk factors. The risk of NAFLD increased with the number of risk factors. Conclusions:The incidence of NAFLD in rural Uygur ethnic group residents in Xinjiang Production and Construction Corps was relatively low, but most residents had one or more risk factors for NAFLD. Prevention and control of NAFLD in this population cannot be ignored. In addition, people of older age, divorced or widowed, low education level, overweight or obese, hypertension, and abnormal eGFR, HDL-C, LDL-C, and ALT were the high-risk groups of NAFLD that need to be paid attention to in this population.

Objective     To investigate the safety and feasibility of day surgery for patients with palmar hyperhidrosis based on the principles of enhanced recovery after surgery (ERAS). Methods     We retrospectively reviewed the medical records of consecutive patients who underwent endoscopic thoracic sympathicotomy (ETS) in the First Affiliated Hospital of Xi'an Jiaotong University from March 2020 to December 2021. Patients were divided into a day surgery group and a conventional group according to their perioperative management methods. The patients in the day surgery group underwent an optimized perioperative procedure under the guidance of ERAS, and were ventilated with a laryngeal or face mask during the operation. The patients in the conventional group completed the preoperative examination, operation and postoperative observation according to the conventional procedures, and were intubated with a single-lumen endotracheal tube. The demographic characteristics, operation time, hospital stay, postoperative complications, and hospitalization cost were compared between the two groups. Results     Finally 172 patients were collected, including 90 males and 82 females, with an average age of 25.97±7.43 years. There were 86 patients in each group. All patients ceased suffering from palmar sweating after surgery. No patient experienced massive bleeding or conversion to thoracotomy. There was no statistical difference in operation time between the two groups (P=0.534). Patients in the day surgery group were discharged within 24 hours. The average hospital stay in the conventional group was 2.09±0.41 days. Incidence of postoperative respiratory complications, and the hospitalization cost of the day surgery group were significantly lower than those of the conventional group (P<0.001). The satisfaction rate in both groups was greater than 95%. Conclusion     Day surgery for patients with palmar hyperhidrosis based on the principles of ERAS is safe and feasible, which can reduce postoperative complications, shorten the length of hospital stay and save the cost of hospitalization.

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Angiotensin II/pharmacology* ; Fibroblasts ; Mice, Inbred C57BL ; Fibrosis ; Collagen/pharmacology* ; Collagen Type I/metabolism* ; RNA, Messenger/metabolism* ; Myocardium/pathology*

OBJECTIVE: To explore the proliferation inhibitory effect of quinones from Blaps rynchopetera defense secretion on colorectal tumor cell lines. METHODS: Human colorectal cancer cell HT-29, human colorectal adenocarcinoma cell Caco-2 and normal human colon epithelial cell CCD841 were chosen for the evaluation of inhibitory activity of the main quinones of B. rynchopetera defense secretion, including methyl p-benzoquinone (MBQ), ethyl p-benzoquinone (EBQ), and methyl hydroquinone (MHQ), through methyl thiazolyl tetrazolium assay. The tumor-related factors, cell cycles, related gene expressions and protein levels were detected by enzyme-linked immunosorbent assy, flow cytometry, RT-polymerase chain reaction and Western blot, respectively. RESULTS: MBQ, EBQ, and MHQ could significantly inhibit the proliferation of Caco-2, with half maximal inhibitory concentration (IC₅₀) values of 7.04 ± 0.88, 10.92 ± 0.32, 9.35 ± 0.83, HT-29, with IC₅₀ values of 14.90 ± 2.71, 20.50 ± 6.37, 13.90 ± 1.30, and CCD841, with IC₅₀ values of 11.40 ± 0.68, 7.02 ± 0.44 and 7.83 ± 0.05 µg/mL, respectively. Tested quinones can reduce the expression of tumor-related factors tumor necrosis factor α, interleukin (IL)-10, and IL-6 in HT-29 cells, selectively promote apoptosis, and regulate the cell cycle which can reduce the proportion of cells in the G₁ phase and increase the proportion of the S phase. Meanwhile, tested quinones could up-regulate mRNA and protein expression of GSK-3β and APC, while down-regulate that of β-catenin, Frizzled1, c-Myc, and CyclinD1 in the Wnt/β-catenin pathway of HT-29 cells. CONCLUSION Quinones from B. rynchopetera defense secretion could inhibit the proliferation of colorectal tumor cells and reduce the expression of related factors, which would be functioned by regulating cell cycle, selectively promoting apoptosis, and affecting Wnt/β-catenin pathway-related mRNA and protein expressions.
Humans ; beta Catenin/metabolism* ; Caco-2 Cells ; Quinones/pharmacology* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Cell Proliferation ; Colorectal Neoplasms/metabolism* ; Cell Line, Tumor ; Apoptosis ; Benzoquinones/pharmacology* ; RNA, Messenger ; Wnt Signaling Pathway

Objective:To investigate the association of cardiovascular diseases (CVD) with triglyceride glucose index (TyG) and TyG-related indicators in Uyghur populations of The Xinjiang Production and Construction Corps.Methods:Based on the cohort of the Uygur population of The Xinjiang Production and Construction Corps, 11 833 study subjects were included. The Kaplan-Meier method was used to estimate the cumulative incidence of CVD in each quartile of TyG and TyG-related indicators. Cox proportional hazards regression model was used to evaluate the relationship between TyG and CVD, TyG-related indicators and CVD. Framingham CVD risk score model (Framingham model) was used to evaluate whether the addition of TyG and TyG-related indicators could improve the predictive ability of the model. The potential mediating role of the TyG in the association between obesity and CVD was examined through mediation effect analysis.Results:The average age of the subjects was (37.00±13.67) years-old, and 51.0% were male. The median follow-up time was 5.67 years, with 1 288 CVD events. The cumulative incidence of CVD increased with the increase of TyG and TyG-related indicators quartiles, and compared with the Q1 group, the risk of CVD in the Q4 group of TyG, TyG-BMI, and TyG-WHtR increased by 20% ( HR=1.20, 95% CI: 1.01-1.42), 77% ( HR=1.77, 95% CI: 1.46-2.16) and 68% ( HR=1.68, 95% CI: 1.36-2.09), respectively. After adding TyG, TyG-BMI, and TyG-WHtR to the Framingham model, respectively, the model's area under the curve, net reclassification improvement, and integrated discrimination improvement were improved. In the association between BMI, WHtR, and CVD, the proportion of mediating effects mediated by the TyG index was 10.55% and 11.50%. Conclusions:Elevated levels of TyG and TyG-related indicators were strongly associated with the risk of CVD in the Uyghur population of The Xinjiang Production and Construction Corps, with TyG-BMI being the most closely correlated with CVD. Early monitoring of TyG-BMI helps identify high-risk groups of CVD.

Objective:To analyze whether triglyceride-glucose (TyG) index is associated with increased risk of cardiovascular diseases (CVD) and the value of TyG index in predicting CVD risk among Kazakh and Uighur population of Xinjiang.Methods:In this study, 5 375 Kazakh and Uygur people of Xinyuan county and Jiashi county were selected as the research objects. Subjects were divided into four groups based on the quartile of the TyG index level. Cox regression model was used to analyze the association between TyG index with the risk of CVD. The dose-response relationship between TyG index and CVD risk was described by restricted cubic splines. The area under the receiver operating characteristic curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to estimate the value of TyG index for predicting CVD. Mediating effect analysis was conducted to analyze the mediating effect of TyG index in the association between body mass index and CVD.Results:The age of subjects was 41.06（30.11，53.00）years old, with 46.30%（2 489/5 375）was male. After multivariate adjustment, there was an increasing trend between the risk of CVD and the higher TyG index Ptrend<0.001, compared with subjects of TyG index in Q1, the HR (95% CI) of Q2, Q3, and Q4 groups was 1.53, 1.23 and 1.73, respectively. Restricted cubic splines showed that TyG index was the linearly associated with the risk of CVD. TyG index could improve the prediction ability of Framingham model for the risk of CVD (NRI=0.106, P=0.010; IDI=0.003, P=0.030). The mediating effect analysis showed that in the relationship between body mass index and CVD, the TyG index had a mediating effect ( P<0.001), and the ratio of mediating effect was 12.69%. Conclusion:TyG index is an independent predictor of CVD risk among kazakh and Uygur population in Xinjiang and has a good predictive value for the risk of CVD.

Objective:To analyze whether triglyceride-glucose (TyG) index is associated with increased risk of cardiovascular diseases (CVD) and the value of TyG index in predicting CVD risk among Kazakh and Uighur population of Xinjiang.Methods:In this study, 5 375 Kazakh and Uygur people of Xinyuan county and Jiashi county were selected as the research objects. Subjects were divided into four groups based on the quartile of the TyG index level. Cox regression model was used to analyze the association between TyG index with the risk of CVD. The dose-response relationship between TyG index and CVD risk was described by restricted cubic splines. The area under the receiver operating characteristic curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to estimate the value of TyG index for predicting CVD. Mediating effect analysis was conducted to analyze the mediating effect of TyG index in the association between body mass index and CVD.Results:The age of subjects was 41.06（30.11，53.00）years old, with 46.30%（2 489/5 375）was male. After multivariate adjustment, there was an increasing trend between the risk of CVD and the higher TyG index Ptrend<0.001, compared with subjects of TyG index in Q1, the HR (95% CI) of Q2, Q3, and Q4 groups was 1.53, 1.23 and 1.73, respectively. Restricted cubic splines showed that TyG index was the linearly associated with the risk of CVD. TyG index could improve the prediction ability of Framingham model for the risk of CVD (NRI=0.106, P=0.010; IDI=0.003, P=0.030). The mediating effect analysis showed that in the relationship between body mass index and CVD, the TyG index had a mediating effect ( P<0.001), and the ratio of mediating effect was 12.69%. Conclusion:TyG index is an independent predictor of CVD risk among kazakh and Uygur population in Xinjiang and has a good predictive value for the risk of CVD.

Objective: To establish a method for the determination of acetylacetone in the air of workplace by gas chromatography. Methods: In August 2020, acetylacetone in the air of workplace was collected by silica gel tube, eluted with methanol, separated and detected by gas chromatography with flame ionization detector. The detection limit and precision of the method were also analyzed. Results: The linear range of acetylacetone was 1.95-1950.60 μg/ml with the regression equation of y=0.815x-3.667, and the correlation coefficient was 0.99993. The limit of detection of the method was 0.18 μg/ml and the minimum detection concentration was 0.12 mg/m(3) (collected sample volume was 1.50 L). The within-run precisions were 1.08%-4.11% and the between-run precisions were 1.98%-2.80%. The desorption rates were 99.68%-100.45%. The sealed samples could be kept at least 15 days at room temperature without significant loss. Conclusion: The solvent desorption-gas chromatography method for the determination of acetylacetone has good precision, high sensitivity and simple operation, and is suitable for the determination of acetylacetone in the air of the workplace.
Solvents ; Air Pollutants, Occupational/analysis* ; Chromatography, Gas/methods* ; Workplace