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Bioactive phenazines from an earwig-associated Streptomyces sp.

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Chinese Journal of Natural Medicines 2019年第6期17卷 475-480页

作者： HAN Hao GUO Zhi-Kai ZHANG Bo ZHANG Mei SHI Jing LI Wei JIAO Rui-Hua tan ren-xiang GE Hui-Ming State Key Laboratory of Pharmaceutical Biotechnology Institute of Functional BiomoleculesSchool of Life SciencesNanjing UniversityNanjing 210023China Hainan Provincial Key Laboratory for Functional Components Research and Utilization of Marine Bio-resources Institute of Tropical Bioscience and BiotechnologyChinese Academy of Tropical Agricultural SciencesHaikou 571101China State Key Laboratory Cultivation Base for TCM Quality and Efficacy Nanjing University of Chinese MedicineNanjing 210023China

Three new phenazine-type compounds, named phenazines SA–SC(1–3), together with four new natural products(4–7), were isolated from the fermentation broth of an earwig-associated Streptomyces sp. NA04227. The structures of these compounds were determined by extensive analyses of NMR, high resolution mass spectroscopic data, as well as single-crystal X-ray diffraction measurement. Sequencing and analysis of the genome data allowed us to identify the gene cluster(spz) and propose a biosynthetic pathway for these phenazine-type compounds. Additionally, compounds 1–5 exhibited moderate inhibitory activity against acetylcholinesterase(AChE), and compound 3 showed antimicrobial activities against Micrococcus luteus.

关键词： Earwig-associated actinomycete Phenazine Biosynthetic pathway Antimicrobial activity Acetylcholinesterase inhibitory activity

Study on the secondary metabolites of grasshopper-derived fungi Arthrinium sp.NF2410

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Chinese Journal of Natural Medicines 2020年第12期18卷 957-960页

作者： LI Wei WEI Jing CHEN Dao-Ying WANG Mei-Jing SUN Yang JIAO Fang-Wen JIAO Rui-Hua tan ren-xiang GE Hui-Ming State Key Laboratory of Pharmaceutical Biotechnology Institute of Functional BiomoleculesSchool of Life SciencesNanjing UniversityNanjing 210023China State Key Laboratory of Pharmaceutical Biotechnology Department of Biotechnology and Pharmaceutical SciencesSchool of Life ScienceNanjing UniversityNanjing 210023China State Key Laboratory Cultivation Base for TCM Quality and Efficacy Nanjing University of Chinese MedicineNanjing 210023China

Two new 2-carboxymethyl-3-hexyl-maleic anhydride derivatives,arthrianhydride A(1)and B(2),along with three known compounds 3-5,were isolated from the fermentation broth of a grasshopper-associated fungus Arthrinium sp.NF2410.The structures of new compounds 1 and 2 were determined based on the analysis of the HR-ESI-MS and NMR spectroscopic data.Furthermore,compounds 1 and 2 were evaluated on inhibitory activity against the enzyme SHP2 and both of them showed moderate inhibitory activity against SHP2.

关键词： Grasshopper-associated fungi Secondary metabolites Structure elucidation SHP2 Inhibitory activity

Dalestones A and B, two anti-inflammatory cyclopentenones from Daldinia eschscholzii with an edited strong promoter for the global regulator LaeA-like gene

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Chinese Journal of Natural Medicines 2019年第5期17卷 387-393页

作者： ZHOU Zhen-Zhen ZHU Hong-Jie YANG Cheng-Long LIU Yan-Jun JIANG Nan XIAO Yong-Sheng SHI Li-Yun JIAO Rui-Hua GE Hui-Ming tan ren-xiang State Key Laboratory of Pharmaceutical Biotechnology Institute of Functional Biomolecules Nanjing University State Key Laboratory Cultivation Base for TCM Quality and Efficacy Nanjing University of Chinese Medicine School of Pharmacy Nanjing Medical University

Replacement of the native promoter of the global regulator Lae A-like gene of Daldinia eschscholzii by a strong gpdA promoter led to the generation of two novel cyclopentenone metabolites, named dalestones A and B, whose structures were assigned by a combination of spectroscopic analysis, modified Mosher's reaction, and electronic circular dichroism(ECD). Dalestones A and B inhibit the gene expression of TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.

关键词： Daldinia eschscholzii Global regulator Cyclopentenone

A new cytochalasin from endophytic Phomopsis sp. IFB-E060

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Chinese Journal of Natural Medicines 2014年第7期12卷 512-516页

作者： SHEN Li LUO Qian SHEN Zhi-Ping LI Ling-Yu ZHANG Xiao-Jun WEI Zhong-Qi FU Yi SONG Yong-Chun tan ren-xiang Medical College Yangzhou University State Key Laboratory of Element Organic Chemistry Nankai University Institute of Functional Biomolecules State Key Laboratory of Pharmaceutical Biotechnology Nanjing University

AIM: To study the chemical constituents of the solid culture of the endophyte Phomopsis sp. IFB-E060 in Vatica mangachapoi. METHOD: Isolation and purification were performed through silica gel column chromatography, gel filtration over Sephadex LH-20, ODS column chromatography, and HPLC. Structures of the isolated compounds were elucidated by a combination of spectroscopic analyses(UV, CD, IR, MS, 1D, and 2D NMR). The cytotoxicity of the isolates was evaluated in vitro by the MTT method against the human hepatocarcinoma cell line SMMC-7721. RESULTS: Five compounds were isolated from the solid culture of the endophyte Phomopsis sp. IFB-E060 and their structures were identified as 18-methoxy cytochalasin J(1), cytochalasin H(2),(22E, 24S)-cerevisterol(3), ergosterol(4), and nicotinic acid(5). Compound 1 had an inhibition rate of 24.4% at 10 μg·mL-1 and 2 had an IC50 value of 15.0 μg·mL-1, while a positive control 5-fluorouracil had an inhibition rate of 28.7% at 10 μg·mL-1. CONCLUSION: 18-Methoxy cytochalasin J(1), produced by endophytic Phomopsis sp. IFB-E060, is a new cytochalasin with weak cytotoxicity to the human hepatocarcinoma cell line SMMC-7721.

关键词： Phomopsis sp. Sphaeropsidaceae Vatica mangachapoi Endophyte Cytochalasin

Reduced macular thickness and vascular density in abnormal glucose metabolism patients: A meta-analysis of optical coherence tomography (OCT) and OCT angiography studies

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中华医学杂志(英文版) 2024年第9期137卷 1054-1068页

作者： Fu xiangyu ren xiang Chen Wenyue Chen Danian Department of Ophthalmology West China Hospital Sichuan University Chengdu Sichuan China Research Laboratory of Ophthalmology and Vision Sciences State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu Sichuan China Department of Ophthalmology The People’s Hospital of Guizhou Province Guiyang Guizhou China

Background: Alterations in macular thickness and vascular density before clinically visible diabetic retinopathy (DR) remain inconclusive. This study aimed to determine whether retinal manifestations in abnormal glucose metabolism (AGM) patients differ from those in the healthy individuals.Methods: PubMed, Embase, and Web of Science were searched between 2000 and 2021. The eligibility criteria were AGM patients without DR. Primary and secondary outcomes measured by optical coherence tomography (OCT) and OCT angiography (OCTA) were analyzed and expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). A random-effects model was used in the data synthesis. The potential publication bias for the variables was evaluated using Egger’s test.Results: A total of 86 observational studies involving 13,773 participants and 15,416 eyes were included. OCT revealed that compared to healthy controls, the total macular thickness of AGM patients was thinner, including the thickness of fovea (–0.24, 95% CI [–0.39, –0.08];P = 0.002,I2 = 87.7%), all regions of parafovea (–0.32, 95% CI [–0.54, –0.11];P = 0.003;I2 = 71.7%) and the four quadrants of perifovea; the thickness of peripapillary retinal nerve fiber layer (pRNFL), macular retinal nerve fiber layer (mRNFL), and ganglion cell layer (GCL) also decreased. OCTA indicated that the superficial and deep vascular density decreased, the foveal avascular zone (FAZ) area enlarged, and the acircularity index (AI) reduced in AGM individuals.Conclusions: Retinal thinning and microvascular lesions have occurred before the advent of clinically detectable DR; OCT and OCTA may have the potential to detect these preclinical changes.Registration: PROSPERO; http://www.***.york.***.uk/prospero/; No. CRD42021269885.

关键词： Abnormal glucose metabolism Optical coherence tomography Optical coherence tomography angiography Diabetic retinopathy Prediabetes Meta-analysis

High-throughput and simultaneous inertial separation of tumor cells and clusters from malignant effusions using spiral-contraction-expansion channels

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Microsystems & Nanoengineering 2024年第2期10卷 91-99页

作者： Zhixian Zhu Hui ren Dan Wu Zhonghua Ni Nan xiang School of Mechanical Engineering and Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical InstrumentsSoutheast University211189NanjingChina School of Mechanical Technology Wuxi Institute of TechnologyNo.1600 Gaolang West Road214129WuxiChina Department of Oncology Jiangyin People’s Hospital214400JiangyinChina

Tumor cell clusters are regarded as critical factors in cancer pathophysiology,and increasing evidence of their higher treatment resistance and metastasis compared to single tumor cells has been obtained.However,existing cell separation methods that are designed for single tumor cells cannot be used to simultaneously purify tumor cell clusters.To address this problem,we demonstrated a microfluidic approach for the high-throughput,continuous-flow ternary separation of single tumor cells,tumor cell clusters,and WBCs from clinical pleural or abdominal effusions by coupling slanted spiral channels and periodic contraction-expansion arrays.We first systematically explored the influence of particle size and flow rate on particle focusing.The separation performance indicated that 94.0%of WBCs were removed and more than 97%of MDA-MB-231 tumor cells were recovered at a high flow rate of 3500µL/min.Moreover,more than 90%of tumor cell clusters were effectively preserved after separation.Finally,we successfully applied our device for the ternary separation of single tumor cells,tumor cell clusters,and WBCs from different malignant effusions collected from patients with metastatic cancer.Thus,our spiral-contraction-expansion device has potential as a sample pretreatment tool for the cytological diagnosis of malignant effusions.

关键词： separation contraction removed

Comparative evaluation of SPE methods for biotoxicity assessment of water and wastewater:Linkage between chemical extracting efficiency and biotoxicity outcome

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Journal of Environmental Sciences 2024年第8期142卷 33-42页

作者： Jiawei Zhou Shihao Wang Xiwei He Hongqiang ren Xu-xiang Zhang State Key Laboratory of Pollution Control and Resource Reuse School of EnvironmentNanjing UniversityNanjing 210023China

Biotoxicity assessment results of environmental waters largely depend on the sample extraction protocols that enrich pollutants to meet the effect-trigger thresholds of bioassays.However,more chemical mixture does not necessarily translate to higher combined biotoxicity.Thus,there is a need to establish the link between chemical extracting efficiency and biotoxicity outcome to standardize extraction methods for biotoxicity assessment of environmental waters.This study compares the performance of five different extraction phases in solid phase extraction(SPE),namely HLB,HLB+Coconut,C18 cartridge,C18 disk and Strata-X,and evaluated their chemical extracting efficiencies and biotoxicity outcomes.We quantitatively assessed cytotoxicity,acute toxicity,genotoxicity,estrogenic activity,and neurotoxicity of the extracts using in vitro bioassays and characterized the chemical extracting efficiencies of the SPE methods through chemical recoveries of 23 model compounds with different polarities and total organic carbon.Using Pareto ranking,we identified HLB+Coconut as the optimal SPE method,which exhibited the highest level of water sample biotoxicity and recovered the most chemicals in water samples.We found that the biotoxicity outcomes of the extracted water samples significantly and positively correlated with the chemical extracting efficiencies of the SPE methods.Moreover,we observed synchronous changing patterns in biotoxicity outcome and chemical extracting efficiencies in response to increasing sample volumes per cartridge(SVPC)during SPE.Our findings underscore that higher chemical extracting efficiency of SPE corresponds to higher biotoxicity outcome of environmental water samples,providing a scientific basis for standardization of SPE methods for adequate assessment of biotoxicities of environmental waters.

关键词： Biotoxicity Chemical recovery Solid phase extraction Surface water Wastewater

Elevated brain temperature under severe heat exposure impairs cortical motor activity and executive function

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Journal of Sport and Health Science 2024年第2期13卷 233-244页

作者： xiang ren tan Mary C.Stephenson Sharifah Badriyah Alhadad Kelvin W.Z.Loh Tuck Wah Soong Jason K.W.Lee Ivan C.C.Low Health and Social Sciences Singapore Institute of TechnologySingapore 138683Singapore Human Potential Translational Research Programme Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Centre for Translational Magnetic Resonance Research Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117549Singapore Department of Physiology Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117593Singapore Heat Resilience and Performance Centre Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117510Singapore N.1 Institute for Health National University of SingaporeSingapore 117456Singapore Campus for Research Excellence and Technological Enterprise(CREATE) Singapore 138602Singapore

Background:Excessive heat exposure can lead to hyperthermia in humans,which impairs physical performance and disrupts cognitive function.While heat is a known physiological stressor,it is unclear how severe heat stress affects brain physiology and function.Methods:Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures(T_(re))attained 39.5℃,inducing exertional or passive hyperthermia,respectively.In a separate trial,blended ice was ingested before and during exercise as a cooling strategy.Data were compared to a control condition with seated rest(normothermic).Brain temperature(T_(br)),cerebral perfusion,and task-based brain activity were assessed using magnetic resonance imaging techniques.Results:T_(br)in motor cortex was found to be tightly regulated at rest(37.3℃±0.4℃(mean±SD))despite fluctuations in T_(re).With the development of hyperthermia,T_(br)increases and dovetails with the rising T_(re).Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks,implying a reduced central motor drive in hyperthermic participants(T_(re)=38.5℃±0.1℃).Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive hyperthermia.Executive function was poorer under a passive hyperthermic state,and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital cortex.Conversely,ingestion of blended ice before and during exercise alleviated the rise in both T_(re)and T_(bc)and mitigated heat-related neural perturbations.Conclusion:Severe heat exposure elevates T_(br),disrupts motor cortical activity and executive function,and this can lead to impairment of physical and cognitive performance.

关键词： Brain functional activity Cognition Heat stress Hyperthermia Motor function

Preparation and properties of poly(ethylene glycol)-bpoly( 3-acrylamidophenylboronic acid) glucose responsive particles and their hyaluronic acid-based microneedle patches

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2024年第5期25卷 395-410页

作者： Yichuan HONG Haojie YU Li WANG xiang CHEN Di SHEN Yu WANG Shuning ren Yudi HUANG Jian YANG State Key Laboratory of Chemical Engineering College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310058China Zhejiang-Russia Joint Laboratory of Photo-Electro-Magnetic Functional Materials College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310058China

To overcome the pain and risk of hypoglycemia in insulin administration,glucose-responsive microneedles have been developed by researchers,which could release insulin according to the blood glucose level.We designed a kind of particles by a reversible addition-fragmentation chain transfer(RAFT)method containing a phenylboronic acid group as the sensor of glucose and carrier of insulin.poly(ethylene glycol)(PEG)-2-(dodecylthio(thiocarbonyl)thio)-2-methylpropionic acid(DDMAT)was synthesized as a macromolecular RAFT agent,which was then reacted with 3-acrylamidophenylboronic acid(AAPBA)to synthesize the block copolymer PEG-b-PAAPBA.Glucose-responsive particles loaded with insulin were prepared by self-assembly based on hydrophilic-hydrophobic interactions.Microneedle patches loaded with glucose-responsive particles were prepared using hyaluronic acid as the substrate.The insulin release behavior of the particles in glucose solutions of 0,100,and 400 mg/dL showed significant glucose responsiveness and good biosafety.The results of blood glucose control experiments in rats indicate that a single microneedle patch can effectively maintain normal blood glucose for over 7 h.

关键词： Diabetes Hyaluronic acid Phenylboronic acid(PBA) Glucose responsive hydrogel Microneedles