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*

In this comprehensive review, we delve into the evolution of drug delivery systems in reproductive medicine with a focus on the emerging role of exosomes, a class of extracellular vesicles. Exosomes offer unique advantages in overcoming these challenges due to their inherent biocompatibility, stability, and ability to facilitate targeted delivery. This review provides a detailed examination of exosome biogenesis and their function in cellular communication, setting the stage for understanding their potential as drug delivery vehicles. We explore the mechanisms through which exosomes can be loaded with small molecule drugs and the benefits they offer over synthetic nanoparticles. The review highlights groundbreaking case studies that illustrate the successful application of exosome-mediated drug delivery in reproductive health, including enhancing fertility treatments, supporting gamete and embryo development, and facilitating maternal-fetal communication. This study aims to provide a precise understanding of how exosomal drug delivery can revolutionize treatments for reproductive health disorders, paving the way for future therapeutic applications. Lastly, we touch upon the promising therapeutic implications of exosomal delivery for proteins and genes, offering a window into future treatments for reproductive health disorders.

Phosphohistone H3 (PHH3) is one of the five newly discovered nucleocardial histones. PHH3 with other histones constitute the main protein components in chromatin in eukaryotic. For it reached the maximum value in G2 phase and M phase with mitosis, so it was considered as a specific nuclear fission marker. At present, PHH3 has been proved to be very useful to determine the nuclear fission images of tumor cells, and to distinguish the nuclear fission images from apoptotic bodies and nuclear fragments. This paper reviews the research status of PHH3 in tumors.

Patients undergoing major oncological surgery for head and neck cancer (SHNC) have a particularly high risk of nosocomial infections.We aimed to identify risk factors for ventilator-associated pneumonia (VAP) in patients undergoing SHNC.The study included 465 patients who underwent SHNC between June 2011 and June 2014.The rate of VAP,risk factors for VAP,and biological aspects of VAP were retrospectively evaluated.The incidence of VAP was 19.6％ (n =95) in patients who required more than 48 h of mechanical ventilation.Staphylococcus (37.7％),Enterobacteriaceae (32.1％),Pseudomonas (20.8％),and Haemophilus (16.9％) were the major bacterial species that caused VAP.The independent risk factors for VAP were advanced age,current smoking status,chronic obstructive pulmonary disease,and a higher simplified acute physiology score system II upon admission.Tracheostomy was an independent protective factor for VAP.The median length of stay in the ICU for patients who did or did not develop VAP was 8.0 and 6.5 days,respectively (P =0.006).Mortality among patients who did or did not develop VAP was 16.8％ and 8.4％,respectively (P ＜ 0.001).The potential economic impact of VAP was high because of the significantly extended duration of ventilation.A predictive regression model was developed with a sensitivity of 95.3％ and a specificity of 69.4％.VAP is common in patients who are undergoing SHNC and who require more than 48 h of mechanical ventilation.Therefore,innovative preventive measures should be developed and applied in this high-risk population.

Objective The hsa-miR-106b-25 gene cluster is involved in various biological processes of carcinoma .This study aims at a prediction and function analysis of the hsa-miR-106b-25 gene cluster, miR-106b, miR-93, and miR-25, so as to provide some evidence for further studies on the functions of the three miRNAs and the mechanisms of their interaction . Methods We obtained the sequences of miR-106b, miR-93, and miR-25 from the miRBase, predicted their target genes with TargetScan , PicTar, and miRanda, and used 3 or more experimentally verified target genes from the miRTarbase as the gene set for further bioinformatic analysis .We predic-ted the biological processes of the target genes by GeneOntology analysis and enriched KEGG ( Kyoto Encyclopedia of Genes and Genomes) by pathway analysis, produced protein-protein interaction ( PPI) networks with STRING . Results The target genes of the miR-106b-25 gene cluster were significantly enriched in such biological processes as the regulation of macromolecule metabolism , regulation of metabolic process , and cell cycle process , while the KEGG pathway mainly in glioma, melanoma, prostate cancer , and gallbladder carcino-ma.The proteins encoded by the targeted genes of showed complicated interactions , and those encoded by the KAT2B, PTEN, TP53, CDH1, MDM2, E2F1, RB1, and SMAD7 plaid a core role in the interac-tion network. Conc lusoi n MiRNAs of the miR-106b-25 gene cluster regulate the downstream target proteins involved in tumorigenesis by participating in the cell cycle and cancer signaling pathway .

Objective To compare the co-prescribing patterns of antibacterials between clinic and ER in a tertiary hospi-tal and mine the association rules among drugs in outpatient and emergency prescriptions .Methods The prescribing data of 2009 were sampled and the prescription drugs were classified according to the anatomical therapeutic chemical (ATC) subgroup code .IBM PASW ○R Modeler 14 was used for data processing and statistics ,and the Apriori association analysis model was es-tablished to carry out data mining .Results There were differences between outpatient and emergency prescriptions with anti-microbial in average number of drug items and antibacterials items ,as well as in the distribution of patient age and gender .Ex-pectorants ,cough suppressants and prepared Chinese medicine for “Qing Re Jie Du” played dominant roles in the associations with cephalosporin in outpatient prescription .More association rules in emergency prescriptions were found which were more complicated .The associations between antibacterials and vitamins ,digestive ulcer drugs ,and potassium agents ,as well as an-tibacterial and antibacterials were not found in the outpatient prescriptions .Conclusion The use of antibacterials in the emer-gency is much more frequently than in the clinic ,especially for the inject-able formulations and the combination of antibacteri-als .So it is more necessary to establish a standard for rational use of antibacterials in ER .

Objective To synthetically evaluate the relationship between miR-31 and the prognosis of carcinoma and to investi-gate its related mechanism.Methods The correlative literatures of tumor prognosis were retrieved from the electronic databases PubMed,EMBASE and ISI Web of Science.The pooled hazard ratios (HRs)and 95% confidence interval(95%CI )were extracted. The prognostic data were performed the synthesis analysis.Results A total of 7 trials conformed to the inclusion criteria including accumulated 2 012 cases of carcinoma.Meta-analysis revealed that the decrease of miR-31 expression in the tumor patients had the poor prognosis (HR=0.784,95%CI :0.630-0.974);in the subgroup analysis,the synthesis results adopting the multivariable a-nalysis and China subjects were 3.512 (95%CI :1.797-6.865)and 1.574 (95%CI :1.062-2.333),which indicating that the in-crease of miR-31 expression predicted the poor prognosis;miR-31 had no statistical significance in the digestive system (P >0.05). Conclusion The prognostic role of miR-31 may possess the histological and regional specificity and has the potential as a novel marker.