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Wenqing Wang,1,2,* Chuchu Ye,2,3,* Bing Zhao,1 Yingjie Zheng,4 Ge Zhang,5 Jinghua Su,1 Hong Huang,1 Lipeng Hao,1,2 Mingliang Chen6 1Department of Microbiology, Pudong New Area Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 2Fudan University Pudong Institute of Preventive Medicine, Shanghai, People’s Republic of China; 3Department of Infectious Disease Control and Prevention, Pudong New Area Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 4Department of Epidemiology/Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning/Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 5School of Public Health, Dali University, Yunnan, People’s Republic of China; 6Research and Translational Laboratory of Acute Injury and Secondary Infection, and Department of Laboratory Medicine, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingliang Chen; Lipeng Hao, Email cmlbright@126.com; hlpmail@126.comBackground: The occurrence and dissemination of hypermucoviscous and hypervirulent Klebsiella pneumoniae (hm-hvKp) isolates in clinical settings are a critical public health problem in the world. However, the data on these isolates in community populations are limited. This study aims to understand the prevalence and molecular characteristics of hm-hvKp isolates in community patients in Shanghai, China.Methods: In 2018, an active surveillance system focused on hm-hvKp in community diarrhoeal cases was implemented in Pudong New Area, Shanghai, China, involving 12 sentinel hospitals. The antimicrobial susceptibility of hm-hvKp isolates from fecal samples was tested, and whole-genome sequencing (WGS) was performed to predict the serotypes and sequence types and to identify antimicrobial resistance determinants, virulence determinants, and phylogenetic clusters.Results: The overall prevalence of hm K. pneumoniae isolates was 2.48% (31/1252), with the proportions of 1.76% (22/1252) for hm-hvKp and 0.72% (9/1252) for hm not hv K. pneumoniae. The prevalence of hm-hvKp isolates among different age groups and different months was statistically significant. All the 22 hm-hvKp isolates were susceptible to 20 antimicrobial agents and only carried blaSHV gene, and KL1 and KL2 accounted for eight (36.36%) cases and seven (31.82%) cases, respectively. The eight ST23/KL1 isolates belonged to the predominant CG23-I clade, which typically possessed the virulence determinants profile of rmpA/rmpA2-iro-iuc-ybt-irp-clb. The five ST86/KL2 isolates were assigned to the global clusters ST86/KL2-1 (n=2), ST86/KL2-2 (n=2), ST86/KL2-3 (n=1), all lack of the clb gene. Shanghai ST23/KL1 and ST86/KL2 isolates were closely related to the global isolates from liver abscesses, blood, and urine.Conclusion: Hm-hvKp is carried by the community population of Shanghai, with ST23/KL1 and ST86/KL2 isolates predominant. Hm-hvKp isolates of different continents, different sources, and different virulence levels were closely related. Ongoing surveillance of hm-hvKp isolates in the community population is warranted.Keywords: hypermucoviscous, hypervirulent, Klebsiella pneumoniae, drug resistance determinants, virulence determinants, whole-genome sequencing

Chenglin Ye,1,* Sizhe Zhu,2,* Jingping Yuan,1 Xiuxue Yuan3 1Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, People’s Republic of China; 3Medical College of Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingping Yuan; Xiuxue Yuan, Email yuanjingping@whu.edu.cn; exiuwust@gmail.comPurpose: Crohn’s disease (CD) represents a multifaceted inflammatory gastrointestinal condition, with a profound significance placed on unraveling its molecular pathways to enhance both diagnostic capabilities and therapeutic interventions. This study focused on identifying a robust macrophage-related signatures (MacroSig) for diagnosing CD, emphasizing the role of FPR1 in macrophage polarization and its implications in CD.Patients and Methods: Expression profiles from intestinal biopsies and macrophages of 1804 CD patients were retrieved from the Gene Expression Omnibus (GEO). Utilizing CIBERSORTx, differential expression analysis, and weighted correlation network analysis to to identify macrophage-related genes (MRGs). By unsupervised clustering, distinct clusters of CD were identified. Potential biomarkers were identified via using four machine learning algorithms, leading to the establishment of MacroSig which combines insights from 12 machine learning algorithms. Furthermore, the expression of FPR1 was verified in intestinal biopsies of CD patients and two murine experimental colitis models. Finally, we further explored the role of FPR1 in macrophage polarization through single-cell analysis as well as through the study of RAW264.7 cells and peritoneal macrophages.Results: Two distinct clusters with differential levels of macrophage infiltration and inflammation were identified. The MacroSig, which included FPR1 and LILRB2, exhibited high diagnostic accuracy and outperformed existing biomarkers and signatures. Clinical analysis demonstrated a strong correlation of FPR1 with disease activity, endoscopic inflammation status, and response to infliximab treatment. The expression levels of FPR1 were validated in our CD cohort by immunohistochemistry and confirmed in two colitis mouse models. Single-cell analysis indicated that FPR1 is predominantly expressed in macrophages and monocytes. In vitro studies demonstrated that FPR1 was upregulated in M1 macrophages, and its activation promoted M1 polarization.Conclusion: We developed a promising diagnostic signature for CD, and targeting FPR1 to modulate macrophage polarization may represent a novel therapeutic strategy.Keywords: Crohn’s disease, macrophage, diagnostic signature, FPR1, machine learning

Yonggui Zhang,1 Xianzhong Lin,2 Chen Ye,2 Peiling Zhang3 1Department of Anesthesiology, The Second Hospital of Longyan, Fujian, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of ChinaCorrespondence: Xianzhong Lin, Department of Anesthesiology, the First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, People’s Republic of China, Email lxzyjs@fjmu.edu.cnBackground: With the aging of the population and the increasing incidence of neurological diseases, amnestic mild cognitive impairment (aMCI) has attracted attention. Hyperbaric oxygen (HBO) has gradually shown the potential in the treatment of aMCI as an emerging treatment method in recent times. This study is to observe the effect of HBO on the long-term learning memory of aMCI rats, and investigate the associated mechanisms.Methods: Seventy-two male rats (4-month-old) were randomly divided into control (CON) group, aMCI group, HBO group, 24 rats in each group. Each group was randomly divided into CON1, CON7, CON28; aMCI1, aMCI7, aMCI28; HBO1, HBO7, HBO28, 8 rats in each group. The aMCI model rats were established in aMCI and HBO groups. HBO group was treated with HBO for 7 days. The ethological and cytopathology which include Morris water maze (MWM) test, HE staining, TUNEL staining and the expression of Fas/FasL on neuron membrane were conducted to evaluate the effects of HBO on day 1, day 7 and day 28 after HBO treatment.Results: MWM test showed that the spatial learning and memory ability of the rats decreased in aMCI group, and recovered in HBO group; Compared with aMCI group, the pathological damage of hippocampal nerve cells was alleviated, the number of apoptotic cells was significantly reduced (P < 0.05), and the expression of Fas/FasL on the surface of nerve cell membrane was significantly weakened in HBO group (P < 0.05). There were no significant changes in the spatial learning and memory ability, pathological damage of hippocampal neurons, the number of apoptotic cells, and the changes of Fas/FasL on the surface of hippocampal neurons in HBO1, HBO7, and HBO28 groups (P > 0.05). However, in aMCI1, aMCI7, and aMCI28 groups gradually aggravated (P < 0.05).Conclusion: 1. HBO can improve the long-term learning and memory impairment by attenuating neuronal apoptosis in aMCI rats. 2. Fas/FasL mediated cell receptor death pathway is involved in the apoptosis of hippocampal neurons.Keywords: amnesic mild cognitive impairment, hyperbaric oxygen, apoptosis, learning and memory impairment

Zhangrui Zeng,1,&ast; Yueshuai Wei,1,&ast; Caihong Ye,1 Yuan Jiang,1 Chunlin Feng,1 Tongtong Guo,1 Min Song,1 Yinhuan Ding,1 Ping Zhan,2 Jinbo Liu1 1Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 2Department of Gynaecology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo Liu, Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China, Te/Fax +86 0830 3165730, Email liujb7203@swmu.edu.cnPurpose: The isolation rate of carbapenem-resistant Enterobacter cloacae complex (CREC) is continuously increasing. The aims of this study were to investigate the molecular characteristics and risk factors associated with CREC infections.Methods: Bacterial species were identified using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonik GmbH, Bremen, Germany), and the hsp60 gene was utilized for further typing. Antimicrobial susceptibilities were assessed through the MicroScan WalkAway 96 Plus system (Siemens, Germany) and the microbroth dilution method. Antimicrobial resistance genes were screened through polymerase chain reaction (PCR), while the homologous relationship was assessed using multilocus sequence typing (MLST). Conjugation experiments were performed to verify whether the plasmid could be transferred. Additionally, logistic regression model was employed to analyze risk factors for CREC infections.Results: 32 strains of CREC bacteria were isolated during the study, yet only 20 were retained for preservation. While the isolates demonstrated resistance to the majority of antibiotics, they exhibited high sensitivity to polymyxin B and tigecycline. All isolates carried the blaNDM resistance gene, including 13 blaNDM-1 isolates and 7 blaNDM-5 isolates. MLST homology analysis revealed the presence of seven known ST types and one new ST type. Conjugation experiments confirmed that 13 isolates were capable of transferring the blaNDM resistance gene to Escherichia coli strain EC600. Single-factor analysis identified multiple primary risk factors for CREC infection, but multivariate analysis did not reveal independent risk factors.Conclusion: This study investigates the molecular characteristics and risk factors associated with CREC infections. The detection rate of CREC strains in our hospital is continuously rising and homology analysis suggested that strains might spread in our hospital, emphasizing the importance of implementing effective preventive measures to control the horizontal transmission of plasmid-mediated antimicrobial resistance genes.Keywords: carbapenem-resistant, Enterobacter cloacae complex, antimicrobial resistance, molecular characteristics, risk factors

Jingqian Zhao,1,2,&ast; Chenyu Zhao,1,3,&ast; Tianrong Xun,1 Xiaokang Wang,1 Sui Wei,1,3 Chunxiao Ye,1 Mimi Zhang,1 Dan Guo,4 Xixiao Yang1 1Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 2School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dan Guo; Xixiao Yang, Email nfyyyxb@smu.edu.cn; yaxx@smu.edu.cnPurpose: This study aims to investigate the effects of Huang Gan formula (HGF), a Chinese herbal prescription used for chronic kidney disease (CKD), on the regulation of the gut microbiota and colonic microenvironment of CKD.Methods: CKD rats were induced by 150 mg/kg adenine gavage for 4 weeks, then orally treated with or without 3.6 g/kg or 7.2 g/kg of HGF for 8 weeks. The renal function and structure were analyzed by biochemical detection, hematoxylin and eosin, Masson’s trichrome, Sirius red and immunochemical staining. Average fecal weight and number in the colon were recorded to assess colonic motility. Further, the changes in the gut microbiota and colonic microenvironment were evaluated by 16S rRNA sequencing, RT-PCR or immunofluorescence. The levels of inflammatory cytokines, uremic toxins, and NF-κB signaling pathway were detected by RT-PCR, ELISA, chloramine-T method or Western blotting. Redundancy analysis biplot and Spearman’s rank correlation coefficient were used for correlation analysis.Results: HGF significantly improved renal function and pathological injuries of CKD. HGF could improve gut microbial dysbiosis, protect colonic barrier and promote motility of colonic lumens. Further, HGF inhibited systemic inflammation through a reduction of TNF-α, IL-6, IL-1β, TGF-β 1, and a suppression of NF-κB signaling pathway. The serum levels of the selected uremic toxins were also reduced by HGF treatment. Spearman correlation analysis suggested that high-dose HGF inhibited the overgrowth of bacteria that were positively correlated with inflammatory factors (eg, TNF-α) and uremic toxins (eg, indoxyl sulfate), whereas it promoted the proliferation of bacteria belonging to beneficial microbial groups and was positively correlated with the level of IL-10.Conclusion: Our results suggest that HGF can improve adenine-induced CKD via suppressing systemic inflammation and uremia, which may associate with the regulations of the gut microbiota and colonic microenvironment.Keywords: chronic kidney disease, systemic inflammation, colonic microenvironment, gut-kidney axis

Approximately 1–2 per 100,000 young athletes die from sudden cardiac death (SCD) and extreme exercise may be associated with myocardial scar and arrhythmias. Racehorses have a high prevalence of atrial fibrillation (AF) and SCD but the presence of myocardial scar and inflammation has not been evaluated. Cardiac tissues from the left (LAA) and right (RAA) atrial appendages, left ventricular anterior (LVAPM) and posterior (LVPPM) papillary muscles, and right side of the interventricular septum (IVS-R) were harvested from racehorses with sudden cardiac death (SCD, n = 16) or other fatal injuries (OFI, n = 17), constituting the athletic group (ATH, n = 33), and compared to sedentary horses (SED, n = 10). Horses in the ATH group had myocyte hypertrophy at all sites; increased fibrosis at all sites other than the LAA; increased fibroblast infiltration but a reduction in the overall extracellular matrix (ECM) volume in the RAA, LVAPM, and IVS-R compared to SED horses. In this horse model, athletic conditioning was associated with myocyte hypertrophy and a reduction in ECM. There was an excess of fibrocyte infiltration and focal fibrosis that was not present in non-athletic horses, raising the possibility of an exercise-induced pro-fibrotic substrate. [ABSTRACT FROM AUTHOR]

Plasma toroidal rotation acceleration in the co-current direction introduced by the n = 1 (toroidal mode number) static resonant magnetic perturbation (RMP) has been observed in the EAST tokamak. It strongly depends on the RMP coil configuration, which is manifested by its dependence on δ ϕ U L (phase difference between upper and lower coils) and RMP current. Modeling results from NTVTOK based on the linear plasma response modeled by MARS-F shows that the Neoclassical Toroidal Viscosity (NTV) torque is in the co-current direction because of the dominant contribution from electrons with the condition that the electron normalized collisionality is much lower than that of ions in this experiment. The modeled dependence of core integrated NTV torque modulated by the magnitude of core magnetic perturbation on δ ϕ U L is consistent with the experimental observations. Threshold condition related to normalized collisionality to achieve the transition from rotation braking to acceleration is obtained in the NTV modeling and agrees well with experimental observations. It is shown in the modeling that the discharges with rotation acceleration are located at the regime that electron contribution to NTV is dominant and the torque is in co-current direction, while others with rotation braking are located at the regime that ion contribution to NTV torque is dominant and the torque is in countercurrent direction. Though the modeling results are in qualitative agreement with the experimental results, there is quantity difference between the modeled NTV torque based on linear plasma response and the experimental values. Possible reason is that the 3D fields are underestimated by linear modeling, particularly in the case of RMP field penetration, as demonstrated by the RMP current threshold for the rotation acceleration observed in the experiments. [ABSTRACT FROM AUTHOR]