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Safety assessment of a novel marine multi-stress-tolerant yeast Meyerozyma guilliermondii GXDK6 according to phenotype and whole genome-sequencing analysis

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Food Science and Human Wellness 2024年第4期13卷 2048-2059页

作者： Xueyan Mo Mengcheng Zhou yanmei li lili Yu Huashang Bai Peihong Shen Xing Zhou Haojun Zhu Huijie Sun Ru Bu Chengjian Jiang State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources Guangxi Research Center for Microbial and Enzyme Engineering TechnologyCollege of Life Science and TechnologyGuangxi UniversityNanning 530004China National Engineering Research Center for Non-Food Biorefinery State Key Laboratory of Non-Food Biomass and Enzyme TechnologyGuangxi Research Center for Biological Science and TechnologyGuangxi Academy of SciencesNanning 530007China Guangxi Key Laboratory for Green Processing of Sugar Resources College of Biological and Chemical EngineeringGuangxi University of Science and TechnologyLiuzhou 545006China

The application of microorganisms as probiotics is limited due to lack of safety evaluation.Here,a novel multi-stress-tolerant yeast Meyerozyma guilliermondii GXDK6 with aroma-producing properties was identified from marine mangrove microorganisms.Its safety and probiotic properties were assessed in accordance with phenotype and whole-genome sequencing analysis.Results showed that the genes and phenotypic expression of related virulence,antibiotic resistance and retroelement were rarely found.Hyphal morphogenesis genes(SIT4,HOG1,SPA2,ERK1,ICL1,CST20,HSP104,TPS1,and RHO1)and phospholipase secretion gene(VPS4)were annotated.True hyphae and phospholipase were absent.Only one retroelement(Tad1-65_BG)was found.Major biogenic amines(BAs)encoding genes were absent,except for spermidine synthase(JA9_002594),spermine synthase(JA9_004690),and tyrosine decarboxylase(inx).The production of single BAs and total BAs was far below the food-defined thresholds.GXDK6 had no resistance to common antifungal drugs.Virulence enzymes,such as gelatinase,DNase,hemolytic,lecithinase,and thrombin were absent.Acute toxicity test with mice demonstrated that GXDK6 is safe.GXDK6 has a good reproduction ability in the simulation gastrointestinal tract.GXDK6 also has a strong antioxidant ability,β-glucosidase,and inulinase activity.To sum up,GXDK6 is considered as a safe probiotic for human consumption and food fermentation.

关键词： Meyerozyma guilliermondii Safety assessment Probiotics Marine mangrove microorganisms Whole-genome sequencing analysis

Elevated Kallistatin promotes the occurrence and progression of non-alcoholic fatty liver disease

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1730-1744页

作者： Zhenzhen Fang Gang Shen Yina Wang Fuyan Hong Xiumei Tang Yongcheng Zeng Ting Zhang Huanyi liu yanmei li Jinhong Wang Jing Zhang Anton Gao Weiwei Qi Xia Yang Ti Zhou Guoquan Gao Department of Biochemistry Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China Department of VIP Medical Center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Physical Examination Center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Department of Clinical Laboratory Guangzhou First People's HospitalGuangzhou 510080China Guangdong Key Laboratory of liver Disease Research the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 51008China Department of Health Sciences College of Health SolutionsArizona State UniversityTempeUSA Guangdong Engineering&Technology Research Center for Gene Manipulation and Biomacromolecular Products Sun Yat-Sen UniversityGuangzhou 510080China Guangdong Province Key Laboratory of Diabetology Guangzhou 510o80China Guangdong Province Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,and the development of nonalcoholic steatohepatitis(NASH)might cause irreversible hepatic damage.Hyperlipidemia(HLP)is the leading risk factor for NAFLD.This study aims to illuminate the causative contributor and potential mechanism of Kallistatin(KAL)mediating HLP to NAFLD.221 healthy control and 253 HLP subjects,62 healthy control and 44 NAFLD subjects were enrolled.The plasma KAL was significantly elevated in HLP subjects,especially in hypertriglyceridemia(HTG)subjects,and positively correlated with liver injury.Further,KAL levels of NAFLD patients were significantly up-regulated.KAL transgenic mice induced hepatic steatosis,inflammation,and fibrosis with time and accelerated inflammation development in high-fat diet(HFD)mice.In contrast,KAL knockout ameliorated steatosis and inflammation in high-fructose diet(HFruD)and methionine and choline-deficient(MCD)diet-induced NAFLD rats.Mechanistically,KAL induced hepatic steatosis and NASH by down-regulating adipose triglyceride lipase(ATGL)and comparative gene identification 58(CGl-58)by LRP6/Gas/PKA/GSK3βpathway through down-regulating peroxisome proliferator-activated receptor(PPARy)and up-regulating kruppel-like factor four(KLF4),respectively.CGl-58 is bound to NF-kB p65 in the cytoplasm,and diminishing CGl-58 facilitated p65 nuclear translocation and TNFa induction.Meanwhile,hepatic CGl-58-overexpress reverses NASH in KAL transgenic mice.Further,free fatty acids up-regulated KAL against thyroid hormone in hepatocytes.Moreover,Fenofibrate,one triglyceride-lowering drug,could reverse hepatic steatosis by down-regulating KAL.These results demonstrate that elevated KAL plays a crucial role in the development of HLP to NAFLD and may be served as a potential preventive and therapeutic target.

关键词： GSK3β inflammation elevated

Recent advances in chemical protein synthesis:method developments and biological applications

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Science China Chemistry 2024年第4期67卷 1060-1096页

作者： Suwei Dong Ji-Shen Zheng Yiming li Huan Wang Gong Chen Yongxiang Chen Gemin Fang Jun Guo Chunmao He Honggang Hu Xuechen li yanmei li Zigang li Man Pan Shan Tang Changlin Tian Ping Wang Bian Wu Chuanliu Wu Junfeng Zhao Lei liu State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Division of life Sciences and Medicine University of Science and Technology of ChinaHefei 230027China School of Food and Biological Engineering Engineering Research Center of Bio-processMinistry of EducationHefei University of TechnologyHefei 230009China School of Chemistry and Chemical Engineering Nanjing UniversityNanjing 210023China State Key Laboratory of Elemento-Organic Chemistry Nankai UniversityTianjin 300071China Department of Chemistry Tsinghua UniversityBeijing 100084China Institute of Health Sciences Anhui UniversityHefei 230601China College of Chemistry Central China Normal UniversityWuhan 430079China School of Chemistry and Chemical Engineering South China University of TechnologyGuangzhou 510640China School of Medicine or Institute of Translational Medicine Shanghai UniversityShanghai 200444China Department of Chemistry The University of Hong KongHong Kong 999077China Shenzhen Graduate School Peking UniversityShenzhen 518055China School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of life Sciences University of Science and Technology of ChinaHefei 230026China Department of Chemical Biology Shanghai Jiao Tong UniversityShanghai 200240China Institute of Microbiology Chinese Academy of SciencesBeijing 100101China Department of Chemistry Xiamen UniversityXiamen 361005China School of Pharmaceutical Science Guangzhou Medical UniversityGuangzhou 511436China

The central dogma of modern biology underscores the pivotal roles proteins play in diverse biological processes,the study of which necessitates advanced methods to produce proteins with precision and versatility.Chemical protein synthesis,a powerful approach utilizing chemical reactions for the de novo construction of structurally accurate proteins,has emerged as a transformative tool for studying proteins and generating protein derivatives/mimics inaccessible by natural biological machinery,including post-translationally modified proteins,proteins comprised of unnatural amino acids,as well as mirror-image proteins.This review summarizes recent strides in synthetic method developments for chemical protein synthesis,including innovative techniques in solid-phase peptide synthesis,the challenges presented by difficult sequences in either synthesis or folding and the exploration of novel ligation reactions using both chemical and enzymatic methods.Furthermore,the review also delves into newly developed protocols for site-selective protein modifications and the generation of stapled or macrocyclized peptides/miniproteins,highlighting the power of chemical methods to make structurally diverse proteins.Recent applications of synthetic proteins in investigating post-translational modifications(phosphorylation,lipidation,glycosylation,ubiquitination,etc.),mirror-image biological processes and drug development are further discussed.Together,these topics provide a comprehensive overview of the current landscape of chemical protein synthesis.

关键词： chemical protein synthesis solid-phase peptide synthesis ligation reactions post-translational modifications mirror-image proteins peptide drugs

Application Value of NLR,PLR,LMR,HEART score,and POCT in Early Warning and Accurate Graded Diagnosis of High-Risk Chest Pain in Emergency Medicine

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Journal of Clinical and Nursing Research 2024年第4期8卷 93-98页

作者： Shaochang Ma Chunhua lin yanmei li Yan Chen Guohui Zhang Guandu District People’s Hospital Kunming 650200Yunnan ProvinceChina Guanshang Street Health Service Center Guandu DistrictKunming 650200Yunnan ProvinceChina

Objective: To evaluate the application value of neutrophils/lymphocytes (NLR), platelets/lymphocytes (PLR), lymphocytes/monocytes (LMR), HEART (history, electrocardiogram, age, risk factors, and troponin) score, and point-of- care testing (POCT) in the early warning and precise diagnosis of high-risk chest pain in emergency medicine. Methods: A total of 157 patients with acute chest pain who were admitted to the emergency department and chest pain treatment unit of our hospital between August 2022 and September 2023 were selected. Rapid testing of bedside myocardial markers (ultrasensitive troponin (hs-cTnI), myoglobin (MYO), creatine kinase isoenzyme (CK-MB), D-dimer (D-Dimer), and N-terminal B-type natriuretic peptide precursor (NT-proBNP)) was performed on the patients using a POCT device (ThermoKing BioMQ60proB). A HEART score was used to classify the patients into low (n = 53), intermediate (n = 59), and high-risk (n = 45) groups, and the NLR, PLR, and LMR were calculated. The NLR, PLR, and LMR values were compared among the three groups of patients, and the optimal cutoff values as well as sensitivity and specificity were determined based on receiver operating characteristic (ROC) analysis. Results: The HEART scores of patients in the low-risk, intermediate-risk, and high-risk groups were (2.72 ± 0.24), (4.75 ± 0.56), and (5.32 ± 0.73) respectively, and the differences were statistically significant (P lication of NLR, PLR, LMR, HEART s

关键词： NLR PLR LMR POCT myocardial markers HEART score Emergency high-risk chest pain

Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1230-1243页

作者： Jun Zhou Jiaqi liu Bingjing Wang Nan li Juan liu yanmei Han Xuetao Cao Institute of Immunology Zhejiang University School of MedicineHangzhou 310058China National Key Laboratory of Immunity and Inflammation Institute of ImmunologyNaval Medical UniversityShanghai 200433China Department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100005China Institute of Immunology College of Life SciencesNankai UniversityTianjin 300071China

Memory CD8+T cell generation is crucial for pathogen elimination and effective vaccination against infection.The cellular and molecular circuitry that underlies the generation of memory CD8+T cells remains elusive.Eosinophils can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune defense.Here we report that eosinophils are required for the generation of memory CD8+T cells by inhibiting CD8+T cell apoptosis.Eosinophil-deficient mice display significantly impaired memory CD8+T cell response and weakened resistance against listeria monocytogenes(L.m.)infection.Mechanistically,eosinophils secrete interleukin-4(IL-4)to inhibit JNK/Caspase-3 dependent apoptosis of CD8+T cells upon L.m.infection in vitro.Furthermore,active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+T cell apoptosis during early stage of L.m.infection in vivo.Adoptive transfer of wild-type(WT)eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+T cell memory responses.Together,our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+T cell memory and enhances immune defense against L.m.infection.Our study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.

关键词： impaired immunity spleen

Rationally designed amyloid inhibitors based on amyloid-related structural studies

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Chinese Chemical Letters 2023年第2期34卷 7-17页

作者： Jinjian Hu Yufen Zhao yanmei li Department of Chemistry Key Lab of Bioorganic Phosphorus Chemistry&Chemical BiologyTsinghua UniversityBeijing 100084China Beijing Institute for Brain Disorders Beijing 100069China Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084China Institute of Drug Discovery Technology Ningbo UniversityNingbo 315221China

Amyloid proteins correlate with a series of degenerative diseases. Targeting amyloid aggregation has remained a hot topic in therapeutic studies. Numerous inhibitors have been developed, but very few have been approved for marketing. Meanwhile, the growing knowledge of amyloid structural characteristics provides a basis for the rational design of inhibitors. Here we introduce the high-resolution structural findings of amyloid fibrils in recent years and discuss the reported strategies toward rationally designed inhibitors based on amyloid-related structural studies.

关键词： Amyloid Amyloid structure Degenerative disease Amyloid inhibitor Rational design

The m^(6)A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy

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Genes & Diseases 2024年第2期11卷 993-1008页

作者： Fangyi Yao Fangmin Zhong Junyao Jiang Ying Cheng Shuai Xu Jing liu Jin lin Jing Zhang Shuqi li Meiyong li yanmei Xu Bo Huang Xiaozhong Wang Jiangxi Province Key Laboratory of Laboratory Medicine Jiangxi Provincial Clinical Research Center for Laboratory MedicineDepartment of Clinical LaboratoryThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China

Chronic myeloid leukemia(CML)is a common adult leukemia.Both the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor prognosis.The N6-methyladenine(m^(6)A)modification plays an important regulatory role in various physiological and pathological processes.KIAA1429 is a known m^(6)A regulator,but the biological role of KIAA1429 in CML is unclear.In this study,we observed that the m^(6)A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase CML.Notably,KIAA1429 regulated the total level of RNA m^(6)A modification in the CML cells and promoted the malignant biological behaviors of CML cells,including proliferation,migration,and imatinib resistance.Inhibiting KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis,consequently inhibiting CML proliferation and drug efflux,ultimately increasing the sensitivity of CML cells to imatinib.Moreover,the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their apoptosis.Rucaparib,a recently developed anti-cancer agent,suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell apoptosis.Rucaparib also inhibited the tumorigenesis of CML cells in vivo.The combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to imatinib.Our study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis to up-regulate RAB27B expression,thereby promoting CML progression.Rucaparib exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression.

关键词： Chronic myeloid leukemia KIAA1429 N6-methyladenine RAB27B Rucaparib YTHDF1

Recyclable Fe_(3)O_(4)@Polydopamine(PDA) nanofluids for highly efficient solar evaporation

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Green Energy & Environment 2022年第1期7卷 35-42页

作者： Qingmiao Wang Yi Qin Feifei Jia Shaoxian Song yanmei li Hubei Key Laboratory of Mineral Resources Processing and Environment Wuhan University of TechnologyWuhanHubei Province430070China Department of Mines Metallurgy and Geology EngineeringUniversity of GuanajuatoGuanajuato36000Mexico School of Resources and Environmental Engineering Wuhan University of TechnologyWuhanHubei Province430070China

Volumetric solar evaporations by using light-absorbing nanoparticles suspended in liquids(nanofluids)as solar absorbers have been widely regarded as one of the promising solutions for clean water production because of its high efficiency and low capital cost compared to traditional solar distillation systems.Nevertheless,previous solar evaporation systems usually required highly concentrated solar irradiation and high capital cost,limiting the practical application on a large scale.Herein,for the first time in this work,polydopamine(PDA)-capped nano Fe_(3)O_(4)(Fe_(3)O_(4)@PDA)nanofluids were used as solar absorbers in a volumetric system for solar evaporation.The introduction of organic PDA to nano Fe_(3)O_(4)highly contributed to the high light-absorbing capacity of over 85%in wide ranges of 200–2400 nm because of the existence of numerous carbon bonds and pi(π)bonds in PDA.As a result,high evaporation efficiency of 69.93%under low irradiation of 1.0 kW m^(-2)was achieved.Compared to other nanofluids,Fe_(3)O_(4)@PDA nanofluids also provided an advantage in high unit evaporation rates.Moreover,Fe_(3)O_(4)@PDA nanofluids showed excellent reusability and recyclability owing to the preassembled nano Fe_(3)O_(4),which significantly reduced the material consumptions.These results demonstrated that the Fe_(3)O_(4)@PDA nanofluids held great promising application in highly efficient solar evaporation.

关键词： Fe_(3)O_(4)@Polydopamine Nanofluids Volumetric solar evaporation Recyclability

Cyclic Dinucleotide Self-Assembled Nanoparticles as a Carrier-Free Delivery Platform for STING-Mediated Cancer Immunotherapy

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CCS Chemistry 2024年第1期6卷 177-195页

作者： Lang Zhao Shao-Hua Zhuo Tian-Yang Wang Jun-Jun Wu Jing-Yun Su Wen-Hao li Bo-Dou Zhang Yan-Mei li Key Lab of Bioorganic Phosphorus Chemistry&Chemical Biology Department of ChemistryTsinghua UniversityBeijing 100084 Beijing Institute for Brain Disorders Beijing 100069 Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084

Cyclic dinucleotides(CDNs)are natural agonists of the stimulator of interferon genes(STING),which is an attractive immunotherapy target.Currently,CDNs and their derivatives are being investigated clinically.However,the poor bioavailability of exogenous CDNs has limited their application in immunotherapy.Although nanocarriers are widely used for cytosolic delivery of CDNs,their loading capacity is insufficient,and their complicated composition and purification process raises bio-compatibility concerns.Herein,we report a super-simplified CDN self-assembly strategy for carrier-free delivery of CDNs.In the presence of excess K^(+),CDNs form oligomers which further self-assemble with divalent metal ions(such as Mn^(2+))to form nanoparticles(NPs)in aqueous solution.We demonstrate that the self-assembled CDN NPs promote cellular uptake of CDNs and enhance tumor immunogenicity by remodeling the tumor microenvironment,inducing immunogenic tumor cell death and increasing tumorinfiltrating lymphocytes,which is conducive to the generation of tumor neoantigen-specific T-cell responses.We also demonstrate that the use of CDN NPs alone or in combination with immune checkpoint blockades inhibits tumor growth,highlighting the fact that CDN NPs are a potent platform for cancer immunotherapy.

关键词： cyclic dinucleotide STING carrierfree delivery tumor immunogenicity cancer immunotherapy