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Detecting SARS-coV-2 BA.2,BA.4,and BA.5 Variants Utilizing a Robust RT-RPA-CRISPR/Cas12a-Based Method-China,2023

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China CDC weekly 2023年第26期5卷 584-591页

作者： Meihui Luo Yang Pan Yaqing He Ruhan A Changcheng Wu Baoying Huang Roujian Lu Li Zhao Bo Peng Fei Ye Huijuan Wang Yuda Chen Zhen Li Daitao Zhang Wenling Wang Wenjie Tan MHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChina CDCBeijingChina Beijing Center for Disease Prevention and control BeijingChina Microbiology Laboratory Shenzhen Center for Disease Control and PreventionShenzhen CityGuangdong ProvinceChina School of Public Health Baotou Medical CollegeBaotou CityInner Mongolia Autonomous RegionChina collaborative innovation centre for regenerative medicine and medical BioResourse development and application co-constructed by the province and ministry Guangxi Medical UniversityGuangxi Zhuang Autonomous RegionChina

Introduction:Since 2019,numerous variants of concern for severe acute respiratory syndrome virus 2(SARS-coV-2)have emerged,leading to significant outbreaks.The development of novel,highly accurate,and rapid detection techniques for these new SARScoV-2 variants remains a primary focus in the ongoing efforts to control and prevent the coronavirus disease 2019(coVID-19)pandemic.Methods:Reverse transcription-recombinase polymerase amplification combined with the clustered regularly interspaced short palindromic repeatsassociated protein 12a(CRISPR/Cas12a)system was used to validate the detection of the Omicron BA.2,BA.4,and BA.5 variants of SARS-coV-2.Results:Our results demonstrate that the CRISPR/Cas12a assay is capable of effectively detecting the SARS-coV-2 BA.2,BA.4,and BA.5 variants with a limit of detection of 10,1,and 10 copies/μL,respectively.Importantly,our assay successfully differentiated the three SARS-coV-2 Omicron strains from one another.Additionally,we evaluated 46 SARS-coV-2 positive clinical samples consisting of BA.2(n=20),BA.4(n=6),and BA.5(n=20)variants,and the sensitivity of our assay ranged from 90%to 100%,while the specificity was 100%.Discussion:This research presents a swift and reliable CRISPR-based method that may be employed to track the emergence of novel SARS-coV-2 variants.

关键词： CRISPR/Cas limit specificity

Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17^(+) γδ T cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第4期24卷 312-325页

作者： Pan LIU Mingfu LIU Deshuang XI Yiguang BAI Ruixin MA Yaomin MO Gaofeng ZENG Shaohui ZONG Department of Spine Osteopathic the First Affiliated Hospital of Guangxi Medical UniversityNanning 530021China Department of Orthopaedics the Third Affiliated Hospital of Xinxiang Medical UniversityXinxiang 453000China Department of Orthopaedics Nanchong Central Hosipitalthe Second Clinical Institute of North Sichuan Medical CollegeNanchong 637000China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanning 530021China college of Public Hygiene of Guangxi medical University Nanning 530021China

Spinal cord injury(SCI)causes motor,sensory,and autonomic dysfunctions.The gut microbiome has an important role in SCI,while short-chain fatty acids(SCFAs)are one of the main bioactive mediators of microbiota.In the present study,we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI.Allen’s method was utilized to establish an SCI model in Sprague-Dawley(SD)rats.The animals received water containing a mixture of 150 mmol/L SCFAs after SCI.After 21 d of treatment,the Basso,Beattie,and Bresnahan(BBB)score increased,the regularity index improved,and the base of support(BOS)value declined.Spinal cord tissue inflammatory infiltration was alleviated,the spinal cord necrosis cavity was reduced,and the numbers of motor neurons and Nissl bodies were elevated.Enzyme-linked immunosorbent assay(ELISA),real-time quantitative polymerase chain reaction(qPCR),and immunohistochemistry assay revealed that the expression of interleukin(IL)-10 increased and that of IL-17 decreased in the spinal cord.SCFAs promoted gut homeostasis,induced intestinal T cells to shift toward an anti-inflammatory phenotype,and promoted regulatory T(Treg)cells to secrete IL-10,affecting Treg cells and IL-17^(+)γδT cells in the spinal cord.Furthermore,we observed that Treg cells migrated from the gut to the spinal cord region after SCI.The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17^(+)γδT cells in the spinal cord,which inhibits the inflammatory response and promotes the motor function in SCI rats.Our findings suggest that there is a relationship among gut,spinal cord,and immune cells,and the“gut-spinal cord-immune”axis may be one of the mechanisms regulating neural repair after SCI.

关键词： Short-chain fatty acids(SCFAs) Spinal cord injury(SCI) Regulatory T cells IL-17^(+)γδT cells Neuroprotection Inflammation Motor function recovery

HIV-1 Transmission among Injecting Drug Users is Principally Derived from Local Circulating Strains in Guangxi, China

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Biomedical and Environmental Sciences 2023年第5期36卷 418-430页

作者： CEN Ping LIANG Hua Yue YANG Yuan ZHANG Fei YANG Shi Xiong MO Ju cong FENG Yi HUANG Jie Gang NING Chuan Yi HUANG Chun Yuan YANG Yao LIANG Na LIANG Bing Yu YE Li LIANG Hao Guangxi Key Laboratory of AIDS Prevention and Treatment School of Public HealthGuangxi Medical UniversityNanning 530021GuangxiChina Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Life Science InstituteGuangxi Medical UniversityNanning 530021GuangxiChina Nanning Center for Disease control and Prevention Nanning 530023GuangxiChina State Key Laboratory of Infectious Disease Prevention and control(SKLID) Chinese Center for Disease Control and Prevention(China CDC)Collaborative Center for Diagnosis and Treatment of Infectious DiseaseBeijing 102206China

Objective The mode of human immunodeficiency virus(HIV) transmission via injection drug use(IDU)still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi.Methods We performed a molecular epidemiological investigation of infections across Guangxi from2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.Results Among the 535 subjects, CRF08_BC(57.4%), CRF01_AE(28.4%), and CRF07_BC(10.7%) were the top 3 HIV strains;72.6% of infections were linked to other provinces in the transmission network;93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces,predominantly Guangdong and Yunnan;92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs.conclusion HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces.coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.

关键词： HIV-1 Injection drug use Transmission Strain source Phylogenetics

mNGS-based dynamic pathogen monitoring for accurate diagnosis and treatment of severe pneumonia caused by fungal infections

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生物安全与健康(英文) 2023年第3期5卷 138-143页

作者： Zhen Li Changcheng Wu Li-An Tang Yinjie Liang Ruhan A Debin Huang Chuanyi Ning Wenling Wang Wenjie Tan collaborative innovation centre of regenerative medicine and medical BioResourse development and application co-constructed by the province and ministry Guangxi Medical UniversityNanning 530021China NHC Key Laboratory of Biosafety National Insttute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBejing 102206China The First Affliated Hospital of Guangxi medical University Nanning 530021China School of Nursing Guangxi Medical UniversityNanning 530021China

Metagenomic next-generation sequencing(mNGs)has been widely applied to identify pathogens associated with infectious diseases.However,limited studies have explored the use of mNGs-based dynamic pathogen monitoring in intensive care unit patients with severe pneumonia.Here,we present a clinical case of an 86-year-old male patient with severe pneumonia caused by a fungal infection.During the clinical treatment,four mNGS analyses were performed within two consecutive weeks.Various respiratory fungal pathogens,including Candida orthopsilosis,Candida albicans,and Aspergillus fumigatus were detected by mNGS of bronchoalveolar lavage fluid(BALF).Based on conventional pathogen identification and clinical symptoms,the patient was diagnosed with severe pneumonia caused by a fungal infection.The abundance of fungal species decreased gradually in response to antifungal and empirical therapies,and the fungal infections were effectively con-trolled.In summary,our results demonstrated that mNGS could effectively identify pathogens in patients with severe pneumonia.Additionally,dynamic pathogen monitoring based on mNGS could assist in the precise diag-nosis of complex infections and may facilitate rapid induction of the most appropriate therapy.

关键词： Metagenomic next-generation sequencing Severe pneumonia Dynamic detection Precision diagnosis Respiratory pathogens

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Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

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Zoological Research 2024年第3期45卷 617-632页

作者： Jing-Hang Jiang Yi-Fu Wang Jie Zheng Yi-Ming Lei Zhong-Yuan Chen Yi Guo Ya-Jie Guo Bing-Qian Guo Yu-Fang Lv Hong-Hong Wang Juan-Juan Xie Yi-Xuan Liu Ting-Wei Jin Bi-Qi Li Xiao-Shu Zhu Yong-Hua Jiang Zeng-Nan Mo Center for Genomic and Personalized medicine Guangxi Collaborative Innovation Center for Genomic and Personalized MedicineGuangxi Key Laboratory for Genomic and Personalized MedicineGuangxi Medical UniversityNanningGuangxi 530021China Department of Urology First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530021China Reproductive medicine Center Jingmen People’s HospitalJingChu University of Technology Affiliated Central HospitalJingmenHubei 448000China School of computer Science and Engineering Yulin Normal UniversityYulinGuangxi 537000China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanningGuangxi 530021China Department of Pathology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China Department of Obstetrics and Gynecology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://***:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

关键词： Tree shrew Adrenal gland Dehydroepiandrosterone Genome-wide association studies Disease model

Natural Morin-Based Metal Organic Framework Nanoenzymes Modulate Articular Cavity Microenvironment to Alleviate Osteoarthritis

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Research 2023年第4期2023卷 163-180页

作者： Jinhong Cai Lian-feng Liu Zainen Qin Shuhan Liu Yonglin Wang Zhengrong Chen Yi Yao Li Zheng Jinmin Zhao Ming Gao Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry The First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration Guangxi Key Laboratory of Regenerative MedicineThe First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Department of Ultrasound Guangxi Medical University Cancer HospitalNanning530021China Department of Orthopedics The First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Life Sciences Institute Guangxi Medical UniversityNanning530021China.

Osteoarthritis(OA)is always characterized as excessive reactive oxygen species(ROS)inside articular cavity.Mimicking natural metalloenzymes with metal ions as the active centers,stable metal organic framework(MOF)formed by natural polyphenols and metal ions shows great potential in alleviating inflammatory diseases.Herein,a series of novel copper-morin-based MOF(CuMHs)with different molar ratios of Cu^(2+)and MH were employed to serve as ROS scavengers for OA therapy.As a result,CuMHs exhibited enhanced dispersion in aqueous solution,improved biocompatibility,and efficient ROS-scavenging ability compared to MH.On the basis of H_(2)O_(2)-stimulated chondrocytes,intracellular ROS levels were efficiently declined and cell death was prevented after treated by Cu_(6)MH(Cu^(2+)and MH molar ratio of 6:1).Meanwhile,Cu_(6)MH also exhibited efficient antioxidant and anti-inflammation function by down-regulating the expression of IL6,MMP13,and MMP3,and up-regulating cartilage specific gene expression as well.Importantly,Cu_(6)MH could repair mitochondrial function by increasing mitochondrial membrane potential,reducing the accumulation of calcium ions,as well as promoting ATP content production.In OA joint model,intra-articular(IA)injected Cu_(6)MH suppressed the progression of OA.It endowed that Cu_(6)MH might be promising nanoenzymes for the prevention and treatment of various inflammatory diseases.

关键词： Osteoarthritis prevention inflammation

Preoperative virtual reduction method for pelvic fractures based on statistical shape models and partial surface data

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Biomimetic Intelligence & Robotics 2023年第4期3卷 67-74页

作者： Wei Kou Yaoyao He Xiao Cheng Zhewei Wang Yuan Yang Shaolong Kuang Department of Mechanical and Electrical Engineering Soochow UniversitySuzhou 215021China Applied Technology college Soochow UniversitySuzhou 215325China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanning 530021China college of Health Science and Environment Engineering Shenzhen Technology UniversityShenzhen 518118China

Virtual reduction is crucial for successful and accurate reduction of pelvic fractures.Various methods have been proposed in this regard.However,not all of them are applicable to every pelvic fracture.Among these methods,the efficiency and accuracy of the method based on statistical shape models in clinical applications require further improvement.This study proposes a virtual reduction method for pelvic fractures that uses statistical shape models and partial surface data of a broken pelvis.Simulated fracture and clinical case experiments were conducted to validate the accuracy and effectiveness of the proposed method.The simulated fracture experiments yielded an average error of 1.57±0.39 mm and a maximum error of 12.82±3.54 mm.The virtual reduction procedure takes approximately 40 s.Based on three clinical case experiments,the proposed method achieves an acceptable level of accuracy compared with manual reduction by a surgeon.The proposed method offers the advantages of shorter virtual reduction times and satisfactory reduction accuracy.In the future,it will be integrated into the preoperative planning system for pelvic fracture reduction,thereby improving patient outcomes.

关键词： Preoperative planning Virtual reduction Statistical shape model Pelvic fractures

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan province,China,2014–2020

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生物医学与环境科学:英文版 2023年第9期36卷 800-813页

作者： YU De E XU Yu Jun LI Mu YANG Yuan LIANG Hua Yue ZHONG Shan Mei QIN Cai LAN Ya Nan LI Da Wei YU Ji Peng PANG Yuan QIN Xue Qiu LIANG Hao ZHU Kao Kao YE Li LIANG Bing Yu Guangxi Key Laboratory of AIDS Prevention and Treatment School of Public HealthGuangxi Medical UniversityNanning 530021GuangxiChina International School of Public Health and One Health Hainan Medical UniversityHaikou 571199HainanChina Prevention and Treatment Department the Fifth People's Hospital of Hainan Province&Affiliated Dermatology Hospital of Hainan Medical UniversityHaikou 570102HainanChina Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Life Sciences InstituteGuangxi Medical UniversityNanning 530021GuangxiChina Oncology medical college Guangxi Medical UniversityNanning 530021GuangxiChina The First Clinical medical college Guangxi Medical UniversityNanning 530021GuangxiChinaGuangxi Key Laboratory of AIDS Prevention and TreatmentSchool of Public HealthGuangxi Medical UniversityNanning 530021GuangxiChina

Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

关键词： HIV-1 subtypes Antiretroviral therapy Virological failure Drug resistance

A polyphenol-modified chitosan hybrid hydrogel with enhanced antimicrobial and antioxidant activities for rapid healing of diabetic wounds

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Nano Research 2023年第1期16卷 905-916页

作者： Zejun Xu Guiting Liu Li Zheng Jun Wu The State Key Laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan UniversityChengdu 610065China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-Sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration Life Science InstitutesGuangxi Medical UniversityNanning 530021China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanning 530021China Bioscience and Biomedical Engineering Thrust The Hong Kong University of Science and Technology(Guangzhou)Guangzhou 511400China Division of Life Science The Hong Kong University of Science and TechnologyHong Kong 999077China

High oxidative stress injury and bacterial infection are the main challenges that impair wound healing in diabetic patients.Therefore,a hydrogel with enhanced antimicrobial and antioxidant properties was developed for rapid healing of diabetic wounds.In this study,chitosan methacrylate-gallic acid(CSMA-GA)polymer with antioxidant activity,antimicrobial activity,and ultraviolet(UV)-triggered gelling properties was developed as a hydrogel precursor.Meanwhile,amphiphilic Pluronic F127 molecules were used to load hydrophobic chlorhexidine drug molecules to obtain F127/chlorhexidine nanoparticle(NP)with strong antibacterial activity.Subsequently,F127/chlorhexidine NPs were encapsulated in CSMA-GA hydrogel to further enhance its antibacterial activity.The hybrid hydrogel platform(CSMA-GA/F127/chlorhexidine(CMGFC))exhibited high antibacterial efficiency(>99.9%)and strong reactive oxygen species(ROS)scavenging ability(>80.0%),which effectively protected cells from external oxidative stress(upregulated superoxide dismutase(SOD)and glutathione/oxidized glutathione disulfide(GSH/GSSG)levels and downregulated malondialdehyde(MDA)levels).Moreover,in vivo results proved that the CMGFC hydrogel significantly reduced inflammatory responses(downregulated interleukin-6(IL-6)and upregulated interleukin-10(IL-10)levels),promoted angiogenesis(upregulated vascular endothelial growth factor(VEGF)and platelet endothelial cell adhesion molecule-1(CD 31)levels),and wound healing(enhanced collagen deposition and tissue remodelling).Overall,the CMGFC hydrogel with enhanced antimicrobial and antioxidant properties demonstrated significant potential to enhance diabetic wound healing.

关键词： antimicrobial antioxidant diabetic wound hydrogel