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*

Neurodegenerative diseases are chronic and progressive diseases of the nervous system.Modern studies have shown that intestinal flora disorders,mitochondrial dysfunction and lipid metabolism abnormalities are closely related to the occurrence and development of neurodegenerative diseases,but the treatment methods are limited.Traditional Chinese medicine believes that spleen is the"the foundation of nurture"and the"the source of Qi and blood biochemistry",Qi deficiency leads to insufficient Qi,blood and body fluid metaplasia,brain dysplasia,leading to the occurrence of neurodegenerative diseases.This paper discusses the mechanism of treating neurodegenerative diseases by spleen from the perspective of"intestinal flora,mitochondria and lipids",and concludes that intestinal flora balance is the material basis of spleen function,mitochondrial homeostasis is an important mechanism of the function of"spleen governing transportation and transformation",and abnormal lipid metabolism is an important manifestation of spleen deficiency and phlegm stasis.Intestinal flora,mitochondria and lipid metabolism may be the potential biological basis for the treatment of neurodegenerative diseases by spleen in traditional Chinese medicine.In order to provide ideas for the clinical research and treatment of neurodegenerative diseases.

Neurodegenerative diseases are chronic and progressive diseases of the nervous system.Modern studies have shown that intestinal flora disorders,mitochondrial dysfunction and lipid metabolism abnormalities are closely related to the occurrence and development of neurodegenerative diseases,but the treatment methods are limited.Traditional Chinese medicine believes that spleen is the"the foundation of nurture"and the"the source of Qi and blood biochemistry",Qi deficiency leads to insufficient Qi,blood and body fluid metaplasia,brain dysplasia,leading to the occurrence of neurodegenerative diseases.This paper discusses the mechanism of treating neurodegenerative diseases by spleen from the perspective of"intestinal flora,mitochondria and lipids",and concludes that intestinal flora balance is the material basis of spleen function,mitochondrial homeostasis is an important mechanism of the function of"spleen governing transportation and transformation",and abnormal lipid metabolism is an important manifestation of spleen deficiency and phlegm stasis.Intestinal flora,mitochondria and lipid metabolism may be the potential biological basis for the treatment of neurodegenerative diseases by spleen in traditional Chinese medicine.In order to provide ideas for the clinical research and treatment of neurodegenerative diseases.

Cerebral ischemia reperfusion injury(CIRI)is a secondary brain injury that may occur in patients with ischemic stroke during the process of blood flow recovery.NOD-like receptor protein 3(NLRP3)inflammasome plays an important role in the occurrence and development of CIRI.Regulating the activity of NLRP3 inflammasome can induce cell pyroptosis,induce neuroinflammatory response,promote macrophage/microglial polarization,destroy the blood-brain barrier,affect angiogenesis and neurogenesis,thereby affecting CIRI.Traditional Chinese medicine has obvious advantages in the treatment of CIRI.In this paper,with NLRP3 inflammasome as the core,we systematically elucidated the mechanism of action of traditional Chinese medicines on CIRI,and found that traditional Chinese medicines monomers(such as baicalin,polygalasaponin F)and traditional Chinese medicines compound formulas(such as Huangqi guizhi wuwu decoction,Yiqi shengqing formulation)can inhibit NLRP3 inflammasome activity,reduce inflammatory response and oxidative stress,and improve neuronal injury,thereby reducing CIRI.

Ischemic stroke is the leading cause of disability in China,and treatment options are still very limited.The method of dredging Fu-organs has been proved to have a significant effect in the treatment of ischemic stroke,but its mechanism is not clear.With the progress of brain-gut communication research,more and more evidence shows that brain-gut communication plays an important role during ischemic stroke.Based on the theory of"brain-gut interaction",this paper discusses the mechanism of Tongfu method in the treatment of ischemic stroke,and discusses the intestinal flora,brain-gut peptide,intestinal metabolites,intestinal mucosal barrier and other aspects.It is concluded that Tongfu method can treat ischemic stroke by regulating intestinal flora,brain-gut peptide content,intestinal metabolite content and repairing intestinal mucosal barrier.In order to provide more ideas for elucidating the mechanism of Tongfu method in the treatment of ischemic stroke,it has very important theoretical and clinical value.

Cerebral ischemia-reperfusion injury(CIR1)refers to the recovery of blood supply after cerebral ischemia,which leads to further damage and the dysfunction of brain tissue.Modern medicine has made some progress in the prevention and treatment of CIRI,but it still faces some challenges and limitations.Therefore,it is of great clinical value to find effective interventions to prevent and treat CIRI.AMP-activated protein kinase(AMPK)and its downstream proteins are important targets for the treatment of CIRI and play key roles in the regulation of cellular energy homeostasis.Traditional Chinese medicine for CIRI has multi-target and multi-pathway activities and multiple effects.It can activate a cascade of reactions in the AMPK signaling pathway and can be used to treat CIRI by regulating autophagy,oxidative stress,inflammatory response,and apoptosis,and has achieved certain result.Therefore,this paper summarizes the structure and mechanisms of the AMPK-related signaling pathway,elaborates on its relationship with CIRI,and systematically summarizes the research status of traditional Chinese medicine's ability to regulate the AMPK signaling pathway in the prevention and treatment of CIRI.This paper aims to provide new ideas for the prevention and treatment of CIRI using traditional Chinese medicine and the development of new drugs.

Stroke is a disease that seriously threatens human health.Traditional Chinese medicine believes that turbid phlegm and sthenia fever are common pathological factors of stroke.The early diagnosis of stroke usually depends on advanced imaging techniques,such as MRI and CT,and there is still a lack of diagnostic biomarkers.Therefore,exploring the biological markers of Phlegm-Heat and Bowel-Excess Syndrome of stroke,combining macro-dialectics with micro-dialectics,can provide objective data support for the prevention and treatment of stroke by traditional Chinese medicine,which is of great significance for the diagnosis,treatment and prognosis evaluation of stroke.This paper reviews and summarizes the clinical biochemical indicators,microbiome,genomics,transcriptomics,proteomics,metabolomics and other aspects,aiming to find specific biomarkers related to Phlegm-Heat and Bowel-Excess Syndrome of stroke,so as to provide molecular basis for the objective research system of stroke"syndrome"and new ideas for the study of syndrome essence.

Stroke is a disease that seriously threatens human health.Traditional Chinese medicine believes that turbid phlegm and sthenia fever are common pathological factors of stroke.The early diagnosis of stroke usually depends on advanced imaging techniques,such as MRI and CT,and there is still a lack of diagnostic biomarkers.Therefore,exploring the biological markers of Phlegm-Heat and Bowel-Excess Syndrome of stroke,combining macro-dialectics with micro-dialectics,can provide objective data support for the prevention and treatment of stroke by traditional Chinese medicine,which is of great significance for the diagnosis,treatment and prognosis evaluation of stroke.This paper reviews and summarizes the clinical biochemical indicators,microbiome,genomics,transcriptomics,proteomics,metabolomics and other aspects,aiming to find specific biomarkers related to Phlegm-Heat and Bowel-Excess Syndrome of stroke,so as to provide molecular basis for the objective research system of stroke"syndrome"and new ideas for the study of syndrome essence.

Objective:To explore the current situation of turnover intention of male nurses in Shanghai and its influencing factors.Methods:From March 2017 and August 2017, this study selected 349 male nurses at all levels of hospitals in Shanghai by snowball sampling to carry out questionnaire survey through internet questionnaire distribution platform. The questionnaire consisted of the General Demographic Characteristics, Turnover Intention Scale (TIS) , Maslach Burnout Inventory General Survey (MBI-GS) and the Organization Commitment Scale.Results:Among 349 male nurses in Shanghai, the score of turnover intention was (15.43±3.48) , 274 of them were with a high level of turnover intention accounting for 78.49%. There were statistical differences in the scores of turnover intention among male nurses with different positional titles and night shifts ( P<0.05) . Multiple linear regression analysis showed that the important influencing factors of turnover intention of male nurses included the emotional burnout, emotional commitment, ideal commitment and economic commitment, in which the emotional burnout was the strongest predictor and the emotional commitment was the strongest protective factor. Conclusions:The turnover intention of male nurses is in the high level. The important influencing factors of turnover intention of male nurses include the job burnout and organizational commitment except for positional titles and night shifts. Nursing managers should pay attention to the cultivation of emotions for hospital and profession among male nurses so as to reduce male nurses' turnover intention and stabilize the male nursing team.

Objective To obtain the basic growth parameters of a self-established F1 hybrid CB6F1 C57-ras transgenic mouse model, and to provide basic information for commercialization of this mouse model. Methods F1 hybrid mice (CB6F1) were produced by crossing C57-ras heterozygous transgenic (c-Ha-ras+/-) male mice and wild-type BALB/cJ female mice.The average litter size, weaning rate, sex ratio, growth performance and C57-ras transgenic positive rate were recorded and analyzed.Results The average litter size was eight, weaning rate was 90%, and sex ratio was approximately in accordance with prediction.The average body weight of newborn mice was 1.73 ±0.05 g.The average body weight of 10-week old c-Ha-ras transgenic female and male mice in CB6F1 background was 24.38 ±1.74 g and 29.42 ±1.72g, respectively, which had a significant difference (P<0.01).The c-Ha-ras transgenic positive rate was 46.9%. which was in accordance with genetic rules.Conclusions The F1 hybrid mice (CB6F1) produced by crossing C57-ras heterozygous transgenic ( c-Ha-ras +/-) male mice and wild-type BALB/cJ female mice show normal growth performance and development characteristics, and it can be used for large-scale commercial supply.