Objective:To isolate Yersinia enterocolitica phage and study its biological and genomic characteristics, and explore its application value. Methods:Phages were isolated from cecum of Apodemus chevrieri in the plague focus of wild rodent in Lijiang employing Yersinia enterocolitica (CMCC52301) as the host strain. After purification, proliferation and concentration, the morphology was observed by transmission electron microscope, and the host spectrum of the phage was determined by double-layer plate method. Phage DNA was extracted and sequenced, and the raw sequences data were assembled and visually analyzed, also performed genome functional annotation, phage classification status, phylogenetic tree, genome collinearity analysis, etc. Results:One strain of Yersinia enterocolitica phage was isolated and named vB_Yen_YN301-151, which had a head and a contractile tail. The phage only lysed Yersinia enterocolitica, and could not lyse other tested strains. And at a lysis temperature of 37 ℃, more transparent plaques were observed compared to at a lysis temperature of 21 ℃. The gene structure of this phage was double-stranded DNA, with a genome length of 51 176 bp and a GC content of 46.96%, and 95 genes were predicted to encode 15 structural morphological related proteins, 9 proteins involved in replication and metabolism, 3 DNA assembly functional proteins, 1 phage lysis related protein, and 67 hypothetical proteins. It was identified that the phage belong to the Drexlerviridae family of the Caudoviricetes class, clustered with vB_YenM_534, vB_Yen_X1, vB_YenM_281, and vB_YenM_531 in the phylogenetic tree and exhibited good collinearity with PY100, vB_YenM_ 25, and vB_Yen_X1. Conclusions:The successfully isolated vB_Yen_YN301-151 is a novel phage belonging to the Drexlerviridae family, and its gene encoded proteins are mostly hypothetical proteins. It only lyses Yersinia enterocolitica, with host specificity and has the potential to be used as diagnostic phage for screening Yersinia enterocolitica.

Objective:To isolate Yersinia enterocolitica phage and study its biological and genomic characteristics, and explore its application value. Methods:Phages were isolated from cecum of Apodemus chevrieri in the plague focus of wild rodent in Lijiang employing Yersinia enterocolitica (CMCC52301) as the host strain. After purification, proliferation and concentration, the morphology was observed by transmission electron microscope, and the host spectrum of the phage was determined by double-layer plate method. Phage DNA was extracted and sequenced, and the raw sequences data were assembled and visually analyzed, also performed genome functional annotation, phage classification status, phylogenetic tree, genome collinearity analysis, etc. Results:One strain of Yersinia enterocolitica phage was isolated and named vB_Yen_YN301-151, which had a head and a contractile tail. The phage only lysed Yersinia enterocolitica, and could not lyse other tested strains. And at a lysis temperature of 37 ℃, more transparent plaques were observed compared to at a lysis temperature of 21 ℃. The gene structure of this phage was double-stranded DNA, with a genome length of 51 176 bp and a GC content of 46.96%, and 95 genes were predicted to encode 15 structural morphological related proteins, 9 proteins involved in replication and metabolism, 3 DNA assembly functional proteins, 1 phage lysis related protein, and 67 hypothetical proteins. It was identified that the phage belong to the Drexlerviridae family of the Caudoviricetes class, clustered with vB_YenM_534, vB_Yen_X1, vB_YenM_281, and vB_YenM_531 in the phylogenetic tree and exhibited good collinearity with PY100, vB_YenM_ 25, and vB_Yen_X1. Conclusions:The successfully isolated vB_Yen_YN301-151 is a novel phage belonging to the Drexlerviridae family, and its gene encoded proteins are mostly hypothetical proteins. It only lyses Yersinia enterocolitica, with host specificity and has the potential to be used as diagnostic phage for screening Yersinia enterocolitica.

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Objective:Novel research and development institutions are crucial strategic forces for technological innovation in the new era. This article analyzed the problems faced by novel research and development institutions in medicine field during their construction and operation, and proposed solutions and countermeasure suggestions, aiming to provide theoretical and practical guidance for their future development.Methods:The author summarized the construction experience of similar institutions domestic and international through literature research and multiple case studies, and explored and analyzed the operation and management mechanisms of novel research and development institutions based on the practice of Xiang An Biomedicine Laboratory.Results:The construction of novel research and development institutions in medicine field faced various problems, such as the existence of blind spots in policy support, limited attractiveness to high-level talents, weak self-renewal capabilities, and inadequate incentive and evaluation systems. It was necessary to establish a management model and operation system that were different from those of traditional research and development institutions.Conclusions:Novel research and development institutions in the medical field should fully leverage their systemic advantages to establish efficient management and incentive systems, build a suitable talent pool, and strengthen the transformation of scientific and technological achievements. Government departments at all levels should provide a comprehensive package of policy support, offer stable financial investment during the initial construction phase, and design appropriate evaluation systems.

Objectives To investigate the effects of seasonal changes on peritoneal dialysis associated peritonitis (PDAP) in patients on peritoneal dialysis (PD),and to provide evidence for clinical prevention and treatment of PDAP.Methods All episodes of PD-related peritonitis during clinic follow-up in maintenance PD patients from Jan 1st,2007 to Dec 31st,2015 in Peking University People's Hospital were reviewed.The incidence of peritonitis,laboratory indexes,pathogens and clinical outcomes in different seasons were recorded and analyzed.One-way ANOVA and chi square test were employed to compare the incidence of PDAP and related data in different seasons,and Pearson correlation was used to analyze correlations between PDAP rate and monthly mean temperature and mean humidity.Results During nine years,a total of 119 PD patients occurred 190 times of peritonitis during home PD.The PDAP rate in summer was the highest,0.21 episodes/year,followed by spring (0.16 episodes/year) and autumn (0.16 episodes/risk year),but there was no significant difference among peritonitis rates in four seasons.There were significant positive correlation between monthly mean temperature,monthly mean humidity and the peritonitis rate (mean temperature:r=0.828,P ＜ 0.01;mean humidity r=0.657,P ＜ 0.05).(2) As for bacteria,in Summer the PDAP rate caused by Staphylococcus aureus and Coagulase negative staphylococcus (CoNS),and Gram-negative bacteria was higher than that in other seasons,but there was no statistical difference.There were significant positive correlation between monthly mean temperature,mean humidity and the rate of CoNS peritonitis (mean temperature:r=0.704,P ＜ 0.05;mean humidity:r=0.607,P ＜ 0.05).(3) There were no statistical difference among results of PD related peritonitis in different seasons about general situation,clinical manifestation,causes of peritonitis and laboratory index before peritonitis episodes.PD procedure-related problems were the main cause of peritonitis in summer and autumn.(4) The cure rate of all peritonitis was 90％.The highest cure rate was in autumn and winter,while the lowest cure rate was in summer,but no statistical difference.Among the peritonitis episodes with treatment failure,52.6％ occurred in summer.Conclusions There is some correlation between the rate of PDAP and seasons.Higher temperature and higher humidity were significantly correlated with higher peritonitis rate,especially the rate of CoNS peritonitis.The prognosis of PDAP in summer was relatively poor,with higher proportion of hospitalization and lower cure rate.