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Novel berberine derivatives as adjuvants in the battle against Acinetobacter baumannii: A promising strategy for combating multi-drug resistance

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Chinese Chemical Letters 2024年第10期35卷 334-340页

作者： Liping Zhao Xixi Guo Zhimeng Zhang Xi Lu Qingxuan Zeng Tianyun Fan Xintong Zhang Fenbei Chen Mengyi Xu Min Yuan Zhenjun Li Jiandong Jiang Jing Pang Xuefu You Yanxiang Wang Danqing Song Beijing key laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China state key laboratory for Infectious diseases prevention and control Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseaseNational Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China

The development of resistance against most of the available antibiotics has made Acinetobacter baumannii(***)a pathogen of high *** this study,thirty novel berberine derivatives are rationally designed,synthesized,and evaluated for their synergistic antibacterial activities against *** them,compound 2d shows the most potent synergetic effect to aztreonam against ***,including carbapenem-resistant and extended-spectrumβ-lactamases-producing ***,synergistic effects were observed for the combinations of 2d and different antibacterial used in clinical practices,indicating its potent broad-spectrum antibiotic-sensitizing effects against *** combination of 2d and aztreonam significantly improves the survival rates of *** larvae compared with aztreonam treatment *** studies indicate that 2d inhibits the drug efflux and iron acquisition of the bacteria by targeting the AdeB transporter protein,thus achieving a synergistic antimicrobial efficacy with different antibacterial ***,berberine derivatives represent a new family of antimicrobial adjuvants against ***,with the advantage of dual-function antibacterial effect,and are worthy of further investigation.

关键词： Acinetobacter baumannii Berberine derivatives Rational design Synergistic effect Eflux Ironacquisition

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M6PR interacts with the HA2 subunit of influenza A virus to facilitate the fusion of viral and endosomal membranes

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Science China(Life Sciences) 2024年第3期67卷 579-595页

作者： Yuzhen Hu Li Jiang Guangwen Wang Yangming Song Zhibo Shan Xuyuan Wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng Liling Liu Hualan Chen Chengjun Li state key laboratory for Animal disease control and prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.

关键词： influenza A virus M6PR HA membrane fusion late endosome

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Magnitude and direction of temperature variability affect hospitalization for myocardial infarction and stroke:population-based evidence from Guangzhou,China

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Frontiers of Environmental Science & Engineering 2024年第3期18卷 1-11页

作者： Zhou Yang Murui Zheng Ze-Lin Yan Hui Liu Xiangyi Liu Jie-Qi Jin Jiagang Wu Chun-Quan Ou state key laboratory of Organ Failure Research Department of BiostatisticsGuangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public HealthSouthern Medical UniversityGuangzhou 510515China Guangzhou Center for disease control and prevention Guangzhou 510440China

Relationships between nonoptimal temperatures and cardiovascular disease(CVD)mortality have been well ***,evidence of the association between temperature variability(TV)and CVD morbidity is *** study aimed to quantify the risk and burden of CVD-related hospitalization associated with the magnitude and direction of *** on meteorology and population-based hospitalizations for myocardial infarction(MI)and stroke were collected in Guangzhou,China,from 2013 to *** temperature variability(HTV)was measured as the standard deviation of hourly temperature records over specific exposure *** direction(upward or downward)of HTV was defined as the average daily mean temperature change relative to that of the previous day during the exposure ***-Poisson regression was applied to assess the impact of HTV after adjusting for the daily mean temperature,and the hospitalization fractions attributable to HTV were calculated.A 1℃-increase in HTV was significantly associated with a 2.24%and 1.72%increase in hospitalizations for MI and hemorrhagic stroke(HS)at lag 0–1 d,respectively,and a 1.55%increase in hospitalizations for ischemic stroke(IS)at lag 0–3 *** the study period,5.99%,4.64%,and 4.53%of MI,HS,and IS hospitalizations,respectively,were attributable to *** upward TV exerts acute effects on CVD hospital admissions,whereas the impact of downward TV generally *** findings highlight the importance of the magnitude and direction of temperature fluctuations,in addition to the mean level,in assessing the adverse health impacts of temperature variations.

关键词： Hourly temperature variability Cardiovascular Hospitalization Direction China

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control of highly pathogenic avian influenza through vaccination

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Journal of Integrative Agriculture 2024年第5期23卷 1447-1453页

作者： Xianying Zeng Jianzhong Shi Hualan Chen state key laboratory for Animal disease control and prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin150069China

The stamping-out strategy has been used to control highly pathogenic avian influenza viruses in many countries,driven by the belief that vaccination would not be successful against such viruses and fears that avian influenza virus in vaccinated birds would evolve more rapidly and pose a greater risk to *** this review,we summarize the successes in controlling highly pathogenic avian influenza in China and make suggestions regarding the requirements for vaccine selection and *** addition,we present evidence that vaccination of poultry not only eliminates human infection with avian influenza virus,but also significantly reduces and abolishes some harmful characteristics of avian influenza virus.

关键词： avian influenza control highly pathogenic vaccination

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Investigation of Nasal Mucosal IgA Responses in the Population Following COVID-19 Pandemic — China, September 2022–August 2023

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China CDC weekly 2024年第15期6卷 312-317,I0005页

作者： Boyang Li Lei Zhou Zhilong Chen Yanhan Wen Qian Wang Tao Huang Si Chen Wei Wu Mengxuan Wang Lina Sun Mifang Liang Shiwen Wang Ling Chen Qun Li National Institute for Viral disease control and prevention Chinese Center for Disease Control and PreventionBeijingChina National key laboratory of Intelligent Tracking and Forecasting for Infectious diseases Chinese Center for Disease Control and PreventionBeijingChina Xiamen United Institute of Respiratory Health Xiamen CityFujian ProvinceChina Guangzhou laboratory Guangzhou CityGuangdong ProvinceChina state key laboratory of Respiratory disease Guangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina

What is already known about this topic?Mucosal IgA plays a crucial role in host immunity against respiratory *** studies suggest that it has the potential to mitigate the transmission of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron ***,a comprehensive population-based analysis examining mucosal IgA levels following the winter 2022 wave of the coronavirus disease 2019(COVID-19)pandemic is yet to be *** is added by this report?In our study involving 3,421 participants,we documented IgA responses subsequent to SARS-CoV-2 infection.A significant proportion of individuals sustained increased levels of IgA for over six *** levels were also observed in individuals with prior infections who underwent asymptomatic reinfections,indicating an active production of IgA ***,individuals with multiple vaccinations or severe symptoms tended to display elevated IgA levels after *** are the implications for public health practice?IgA in the nasal mucosa is crucial for defense against SARS-CoV-2 *** insights can enhance our knowledge of immune responses following infection and have provided certain reference values for disease prevention and control strategies.

关键词： prevention sustained immunity

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Molecular Evolution of Protein Sequences and Codon Usage in Monkeypox Viruses

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Genomics, Proteomics & Bioinformatics 2024年第1期22卷 89-97页

作者： Ke-Jia Shan Changcheng Wu Xiaolu Tang Roujian Lu Yaling Hu Wenjie Tan Jian Lu state key laboratory of Protein and Plant Gene Research Center for BioinformaticsSchool of Life SciencesPeking UniversityBeijing 100871China Sinovac Biotech Ltd. Beijing 100085China NHC key laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 100052China

The monkeypox virus(mpox virus,MPXV)epidemic in 2022 has posed a significant public health ***,the evolutionary principles of MPXV remain largely ***,we examined the evolutionary patterns of protein sequences and codon usage in *** first demonstrated the signal of positive selection in OPG027,specifically in the CladeⅠlineage of ***,we discovered accelerated protein sequence evolution over time in the variants responsible for the 2022 ***,we showed strong epistasis between amino acid substitutions located in different *** codon adaptation index(CAI)analysis revealed that MPXV genes tended to use more non-preferred codons compared to human genes,and the CAI decreased over time and diverged between clades,with CladeⅠ>Ⅱa andⅡb-A>Ⅱ*** the decrease in fatality rate among the three groups aligned with the CAI pattern,it remains unclear whether this correlation was coincidental or if the deoptimization of codon usage in MPXV led to a reduction in fatality *** study sheds new light on the mechanisms that govern the evolution of MPXV in human populations.

关键词： Mpox virus Positive selection OPG027 Accelerated evolution Codon usage bias

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A Case of Brucellosis Concomitant with Severe Fever with Thrombocytopenia Syndrome—Weifang City,Shandong Province,China,2023

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China CDC weekly 2024年第27期6卷 677-680页

作者： Qingqing Xu Cuiping Wu Hui Liu Chao Geng Jinhui Zhang Dongri Piao Hongyan Zhao Yu Fan Guozhong Tian Hai Jiang National key laboratory of Intelligent Tracing and Forecasting for Infectious diseases National Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Department of Infectious diseases Yidu Central Hospital of WeifangWeifang CityShandong ProvinceChina Institute of Bacterial disease Jinan Center for Disease Control and PreventionJinan CityShandong ProvinceChina Tongliao Center for disease control and prevention Tongliao CityInner Mongolia Autonomous RegionChina

Summary What is already known about this topic?Brucellosis and severe fever with thrombocytopenia syndrome(SFTS)are neglected zoonoses,attributable respectively to Brucella and the SFTS virus(SFTSV).While the incidence of these diseases has been rising,instances of co-infection remain *** is added by this report?This represents the first documented case of a rare coinfection involving Brucella and SFTSV.

关键词： neglected instance Shandong

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Cinnamaldehyde targets SarA to enhance β-lactam antibiotic activity against methicillin-resistant Staphylococcus aureus

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mLife 2024年第2期3卷 291-306页

作者： Jianguo Li Tingyin Lu Yuefei Chu Yuejun Zhang Jing Zhang Wenzhen Fu Jian Sun Yahong Liu Xiao-Ping Liao Yu-Feng Zhou state key laboratory for Animal disease control and prevention South China Agricultural UniversityGuangzhouChina Guangdong Provincial key laboratory of Veterinary Pharmaceutics Development and Safety Evaluation South China Agricultural UniversityGuangzhouChina Yantai Fushan Center for Animal disease control and prevention YantaiChina

Methicillin-resistant Staphylococcus aureus(MRSA)is a current global public health problem due to its increasing resistance to the most recent antibiotic *** critical approach is to develop ways to revitalize existing ***,we show that the phytogenic compound cinnamaldehyde(CIN)and β-lactam antibiotic combinations can functionally synergize and resensitize clinical MRSA isolates to β-lactam therapy and inhibit MRSA biofilm *** studies indicated that the CIN potentiation effect on β-lactams was primarily the result of inhibition of the mecA expression by targeting the staphylococcal accessory regulator *** alone or in combination with β-lactams decreased sarA gene expression and increased SarA protein phosphorylation that impaired SarA binding to the mecA promoter element and downregulated virulence genes such as those encoding biofilm,α-hemolysin,and *** of SarA-mecA binding thus interfered with PBP2a biosynthesis and this decreased MRSA resistance to β-***,CIN fully restored the anti-MRSA activities of β-lactam antibiotics in vivo in murine models of bacteremia and biofilm ***,our results indicated that CIN acts as a β-lactam adjuvant and can be applied as an alternative therapy to combat multidrug-resistant MRSA infections.

关键词： cinnamaldehyde MRSA SarA β-lactamresistance

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China’s Initiatives and Achievements in Enhancing the Professional Capabilities of CDCs

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China CDC weekly 2024年第38期6卷 979-981页

作者： Hao Chen Ying Cui Kaixuan Liu Chengyu Lai Yuan Wang Qingfeng Chen Zhi Zeng Yang Mei Office of Policy and Planning Research Chinese Center for Disease Control and PreventionBeijingChina Chinese Center for disease control and prevention BeijingChina.

Capacity building is essential for developing a robust disease control and prevention system(1).Recognizing this,on December 25,2023,the General Office of China’s state Council issued the“Guidelines for Promoting the High-Quality Development of disease control and prevention”(hereinafter referred to as the“Guidelines”)(2),emphasizing the need to enhance six key professional capabilities within the disease control and prevention *** Guidelines provide a foundational framework for the future growth and enhancement of centers for disease control and prevention(CDCs).

关键词： Professional prevention system.

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Continued evolution of H10N3 influenza virus with adaptive mutations poses an increased threat to mammals

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Virologica Sinica 2024年第4期39卷 546-555页

作者： Shiping Ding Jiangtao Zhou Junlong Xiong Xiaowen Du Wenzhuo Yang Jinyu Huang Yi Liu Lihong Huang Ming Liao Jiahao Zhang Wenbao Qi state key laboratory for Animal disease control and prevention South China Agricultural UniversityGuangzhou510642China National Avian Influenza Para-Reference laboratory Guangzhou510642China key laboratory of Zoonoses Ministry of Agriculture and Rural AffairsGuangzhou510642China National and Regional Joint Engineering laboratory for Medicament of Zoonoses prevention and control Guangzhou510642China key laboratory of Zoonoses prevention and control of Guangdong Province Guangzhou510642China state key laboratory of Agricultural Microbiology College of Veterinary MedicineHuazhong Agricultural UniversityWuhan430070China College of Animal Science and Technology Zhongkai University of Agriculture and EngineeringGuangzhou510550China

The H10 subtype avian influenza virus(AIV)poses an ongoing threat to both birds and ***,fatal human cases of H10N3 and H10N8 infections have drawn public *** 2022,we isolated two H10N3 viruses(A/chicken/Shandong/0101/2022 and A/chicken/Shandong/0603/2022)from diseased chickens in *** analysis revealed that these viruses were genetically associated with human-origin H10N3 virus,with internal genes originating from local H9N2 *** to the H10N8 virus(A/chicken/Jiangxi/102/2013),the H10N3 viruses exhibited enhanced thermostability,increased viral release from erythrocytes,and accumulation of hemagglutinin(HA)***,we evaluated the pathogenicity of both H10N3 and H10N8 viruses in *** found that viral titers could be detected in the lungs and nasal turbinates of mice infected with the two H10N3 viruses,whereas H10N8 virus titers were detectable in the lungs and brains of ***,the proportion of double HA Q222R and G228S mutations in H10N3 viruses has increased since ***,the functional roles of the Q222R and G228S double mutations in the HA gene of H10N3 viruses remain unknown and warrant further *** study highlights the potential public health risk posed by the H10N3 virus.A spillover event of AIV to humans could be a foretaste of a looming ***,it is imperative to continuously monitor the evolution of the H10N3 influenza virus to ensure targeted prevention and control measures against influenza outbreaks.

关键词： Avian influenza virus(AIV) H10N3 Evolution Pathogenicity

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