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Deciphering fungal metabolon coupling tandem inverse-electrondemand Diels-Alder reaction and semipinacol rearrangement for the biosynthesis of spiro polycyclic alkaloids

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Science China Chemistry 2025年第01期 288-296页

作者： Shuai Liu Wen-Qiang xu Ying-Tong Di Man-Cheng Tang Ding-Kang Chen Ming-Ming Cao Yao-Wen Chang Hong-Yu Tang Chun-Mao Yuan Jun-Bo Yang Zhi-Li Zuo Han Guo zi-fei xu Ying Zeng Yun-Dong Wu Xiao-Jiang Hao Key Laboratory of Phytochemistry and Natural Medicines (Chinese Academy of Sciences) Kunming Institute of Botany Chinese Academy of Sciences University of Chinese Academy of Sciences Lab of Computational Chemistry and Drug Design State Key Laboratory of Chemical Oncogenomics Peking University Shenzhen Graduate School Shenzhen Bay Laboratory State Key Laboratory of Microbial Metabolism School of Life Sciences & Biotechnology Shanghai Jiao Tong University State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University Molecular Biology Experimental Center Germplasm Bank of Wild Species in Southwest China Kunming Institute of Botany Chinese Academy of Sciences Yunnan Key Laboratory for Wild Plant Resources Kunming Institute of Botany Chinese Academy of Sciences Research Unit of Chemical Biology of Natural Anti-Virus Products Chinese Academy of Medical Sciences

In the intricate process of natural product biosynthesis, a metabolon can enhance metabolic flux by associating sequential enzymes. A fungal metabolon, comprising of flavin-dependent monooxygenase Spe F and P450 monooxygenase Spe G, is identified in the biosynthesis of spiro polycyclic alkaloids(+)-notoamide B and its diastereomer(+)-versicolamide B. Using notoamide E as a substance, Spe F/Spe G metabolon can control the stereoselectivity of its 2,3-epoxidation, followed by hydrogen atom ion at C-17 to generate reactive epoxide tau-m A with dienyl iminium unit. Subsequently,(+)-notoamide B and(+)-versicolamide B are produced via tandem nonenzymatic inverse-electron-demand Diels-Alder reaction and semipinacol rearrangement. This provides the first example of metabolon in the biosynthesis of spiro-prenylated indole alkaloids.

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Discovery of daspyromycins A and B,2-aminovinyl-cysteine containing lanthipeptides,through a genomics-based approach

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Chinese Chemical Letters 2022年第1期33卷 511-515页

作者： Jing Shi Jia-Qi Ma Yong-Chao Wang zi-fei xu Bo Zhang Rui-Hua Jiao Ren-Xiang Tan Hui-Ming Ge State Key Laboratory of Pharmaceutical Biotechnology Institute of Functional BiomoleculesSchool of Life SciencesNanjing UniversityNanjing 210023China Chemistry and Biomedicine Innovation Center(ChemBIC) Nanjing UniversityNanjing 210023China

Lanthipeptides are one of the largest groups of ribosomally synthesized and post-translationally modified peptides(RiPPs)and are characterized by the presence of lanthionine(Lan)or methyllanthionine residues(MeLan).Only very few lanthipeptides contain a C-terminal 2-aminovinyl-cysteine(AviCys)motif,but all of them show potent antibacterial *** advances of genome sequencing led to the rapid accumulation of new biosynthetic gene clusters(BGCs)for *** this study,through our genome mining strategy,we found the AviCys containing lanthipeptides are widespread in the bacterial kingdom.A lanthipeptide-type biosynthetic gene cluster was identified from public bacterial genome *** new lanthipeptides,daspyromycins A and B(1 and 2)containing AviCys motif,along with two degraded products,daspyromycins C and D(3 and 4),were obtained after heterologous expression of the gene cluster in Streptomyces albus *** A and B showed potent antimicrobial activity against a spectrum of Gram-positive and-negative bacteria including methicillin-resistant Staphylococcus aureus(MRSA)and vancomycin-resistant Enterococci(VRE).

关键词： Lanthipeptides Genomics-based approach Daspyromycin RiPPs 2-Aminovinyl-cysteine motif

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Deciphering fungal metabolon coupling tandem inverse-electrondemand Diels-Alder reaction and semipinacol rearrangement for the biosynthesis of spiro polycyclic alkaloids

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科学通报 2024年

In the intricate process of natural product biosynthesis, a metabolon can enhance metabolic flux by associating sequential enzymes. A fungal metabolon, comprising of flavin-dependent monooxygenase SpeF and P450 monooxygenase SpeG, is identified in the biosynthesis of spiro polycyclic alkaloids(+)-notoamide B and its diastereomer(+)-versicolamide B. Using notoamide E as a substance, SpeF/SpeG metabolon can control the stereoselectivity of its 2,3-epoxidation, followed by hydrogen atom ion at C-17 to generate reactive epoxide tau-mA with dienyl iminium unit. Subsequently,(+)-notoamide B and(+)-versicolamide B are produced via tandem nonenzymatic inverse-electron-demand Diels-Alder reaction and semipinacol rearrangement. This provides the first example of metabolon in the biosynthesis of spiro-prenylated indole alkaloids.

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Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

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Neural Regeneration Research 2025年第1期20卷 6-20页

作者： Xiu-Yun Zhao De-En xu Ming-Lei Wu Ji-Chuan Liu zi-Ling Shi Quan-Hong Ma Department of Neurology and Clinical Research Center of Neurological Disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Institute of Neuroscience&Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular *** reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and *** this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular *** also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative *** summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve *** review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response

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Clinicopathological differences between patients with schistosomal appendicitis and non schistosomal appendicitis:A retrospectively study of past ten years

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World Journal of Clinical Cases 2025年第2期13卷 24-32页

作者： Xiao-Yi Wang Yao Hao zi-Jian Wang Xiu-Liang xu Jiang-Hua Yang Department of Infectious Diseases The First Affiliated of Wannan Medical CollegeWuhu 241001Anhui ProvinceChina

BACKGROUND Chronic schistosomiasis causes multiple organ and multiple system diseases,especially the digestive *** eggs are mainly deposited in the stomach,liver and colorectal,but a few eggs are deposited in the appendix and cause *** present,there are few studies on schistosomal *** To explore the differences in epidemiological,clinical and pathological characteristics between schistosomal appendicitis and non-schistosomal appendicitis over the past decade in order to assess the impact of schistosomiasis on *** The differences of general data,clinical data and laboratory examination data of patients with appendicitis from October 2013 to October 2023 were retrospectively *** patients were divided into two groups for *** were 136 patients in schistosomal appendicitis group and 5418 patients in non-schistosomal appendicitis *** Schistosomal appendicitis accounted for 2.45%of all patients with appendicitis,and the annual proportion in the past decade was 2.2%,2.9%,1.8%,1.9%,3.4%,3.1%,1.9%,1.6%,3%,2.6%,*** prevalence of schistosomal appendicitis was middle-aged and elderly males,with an average age of 61.73±15.335 *** main population of non-schistosomal appendicitis was middle-aged men,with an average age of 35.8±24.013 years(P<0.001).The distribution of pathological types of appendicitis was different between the two groups(P<0.001).The incidence of acute suppurative appendicitis in non-schistosomal appendicitis was higher than that in schistosomal appendicitis[odds ratio(OR)=0.504;95%confidence interval(CI):0.349-0.728;P<0.001].The proportion of acute attack of chronic appendicitis in schistosomal appendicitis was higher than that in non-schistosomal appendicitis(OR=2.614;95%CI:1.815-3.763;P<0.001).The proportion of schistosomal appendicitis patients complicated with colorectal cancer was higher than that of nonschistosomal appendicitis patients(OR=5.087;95%CI:1.427-

关键词： Schistosomal appendicitis Schistosomiasis Appendix Colorectal cancer Clinicopathological characteristics

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High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

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Neural Regeneration Research 2025年第9期20卷 2611-2623页

作者： Mengshi Yang Miao Bai Yuan Zhuang Shenghua Lu Qianqian Ge Hao Li Yu Deng Hongbin Wu Xiaojian xu fei Niu Xinlong Dong Bin Zhang Baiyun Liu Beijing Tiantan Hospital Capital Medical UniversityBeijingChina Department of Neurology The First Hospital of Tsinghua UniversityBeijingChina Department of Neurotrauma and Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Department of Critical Care Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Center for Nerve Injury and Repair Beijing Institute of Brain DisordersChina National Clinical Research Center for Neurological DiseasesBeijingChina

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently *** potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet *** the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of *** vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial ***,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were ***-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of *** Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our ***-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain *** dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in *** receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain ***,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is th

关键词： apoptosis BV2 microglia dexamethasone glucocorticoid receptor glucocorticoids innate immune system microglial polarization neuroinflammation primary microglia traumatic brain injury

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De novo production of 24-epi-ergosterol in bioengineered yeast

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Chinese Journal of Natural Medicines 2023年第5期21卷 321-322页

作者： xu zi fei DONG Liao-Bin State Key Laboratory of Natural Medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 211198China

Plant natural products(PNPs),a rich source of structurally unique and functionally diverse bioactive compounds,comprise a large variety of natural product families including alkaloids,terpenoids,and phenylpropanoids[1].PNPs possess a wide range of applications such as antibiotics,analgesics,and antiviral,antimalarial and antineoplastic agents[2,3].Classically,collection of PNPs relies on extraction and purification from natural ***,due to their low amounts in nature,the extraction process is often inefficient and *** synthesis,on the other hand,is difficult due to the stereochemical complexity of *** recent years,advances in synthetic biology have accelerated the process of producing complex PNPs in yeast cell *** cerevisiae(yeast)is charaterized by a wealth of well-established tools available for genetic manipulation,a well-characterized core metabolic network,low cultivation cost,and compatibility with high cell density fermentation[4-7].As a result,*** is increasingly used as a workhorse for enzyme characterization,biosynthetic pathway elucidation[8,9],and de novo production for various highvalue PNPs[10].

关键词： horse compatibility cultivation

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Bullous pemphigoid associated with acquired hemophilia A: A case report

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World Journal of Clinical Cases 2025年第4期13卷 28-33页

作者： Su-Ye Hu Meng-Can Li zi-Jia Hao xu-Ya Chai Pei-Sai Li Yang Liu Li-Xia Liu Ying xu Pan-Pan Yang Ling-E Li Department of Dermatology Shijiazhuang Traditional Chinese Medicine HospitalShijiazhuang 050051Hebei ProvinceChina Graduate School Hebei University of Traditional Chinese MedicineShijiazhuang 050051Hebei ProvinceChina Department of Pathology Shijiazhuang Traditional Chinese Medicine HospitalShijiazhuang 050051Hebei ProvinceChina

BACKGROUND Acquired hemophilia A (AHA) is a rare and potentially severe bleeding disordercaused by circulating autoantibodies against factor Ⅷ (FⅧ). In approximately50% of the patients, the condition is associated with autoimmune diseases,cancers, medication use, pregnancy, and the post-partum period. Bullous pemphigoid(BP) is a chronic autoimmune subepidermal blistering disease associatedwith tissue-bound and circulating autoantibodies against BP antigens 180 (BP180)and 230 (BP230). AHA-associated BP has a high mortality rate;hence, the understandingof this disease must *** SUMMARY A 69-year-old man presented with erythema, blisters, blood blisters, and crustsaccompanied by severe pruritus for more than 20 days, and ecchymosis andswelling on his left upper arm for 3 days. Pathological examination revealed asubepidermal blister that contained eosinophils. Laboratory tests showed that theBP180 autoantibody levels had increased, isolated activated partial thromboplastintime was notably prolonged (115.6 s), and coagulation FⅧ activity wasextremely low (< 1.0%). Furthermore, the FⅧ inhibitor titer had greatlyincreased (59.2 Bethesda units). Therefore, the patient was diagnosed as having BP associated with AHA, prescribed 0.05% topical halometasone cream, and transferred to a higher-level hospitalfor effective treatment;however, he died after 2 *** AHA associated BP is rare, dangerous, and has a high mortality rate. Therefore, its timely diagnosis and effectivetreatment are necessary.

关键词： Bullous pemphigoid Acquired hemophilia A Acquired hemophilia A FactorⅧ Case report

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Emphasizing Essential Words for Sentiment Classification Based onRecurrent Neural Networks

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Journal of Computer Science & Technology 2017年第4期32卷 785-795页

作者： fei Hu Li Li zi-Li Zhang Jing-Yuan Wang Xiao-fei xu College of Computer and Information Science Southwest University Chongqing 400715 China Network Centre Chongqing University of Education Chongqing 400065 China

With the explosion of online communication and publication, texts become obtainable via forums, chat messages, blogs, book reviews and movie reviews. Usually, these texts are much short and noisy without sufficient statistical signals and enough information for a good semantic analysis. Traditional natural language processing methods such as Bow-of-Word (BOW) based probabilistic latent semantic models fail to achieve high performance due to the short text environment. Recent researches have focused on the correlations between words, i.e., term dependencies, which could be helpful for mining latent semantics hidden in short texts and help people to understand them. Long short-term memory (LSTM) network can capture term dependencies and is able to remember the information for long periods of time. LSTM has been widely used and has obtained promising results in variants of problems of understanding latent semantics of texts. At the same time, by analyzing the texts, we find that a number of keywords contribute greatly to the semantics of the texts. In this paper, we establish a keyword vocabulary and propose an LSTM-based model that is sensitive to the words in the vocabulary; hence, the keywords leverage the semantics of the full document. The proposed model is evaluated in a short-text sentiment analysis task on two datasets: IMDB and SemEval-2016, respectively. Experimental results demonstrate that our model outperforms the baseline LSTM by 1%similar to 2% in terms of accuracy and is effective with significant performance enhancement over several non-recurrent neural network latent semantic models (especially in dealing with short texts). We also incorporate the idea into a variant of LSTM named the gated recurrent unit (GRU) model and achieve good performance, which proves that our method is general enough to improve different deep learning models.

关键词： short text understanding long short-term memory (LSTM) gated recurrent unit (GRU) sentiment classification deep learning

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Brain-Derived Glia Maturation Factor b Participates in Lung Injury Induced by Acute Cerebral Ischemia by Increasing ROS in Endothelial Cells

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Neuroscience Bulletin 2018年第6期34卷 1077-1090页

作者： fei-fei xu zi-Bin Zhang Yang-Yang Wang Ting-Hua Wang Institute of Neurological Disease Department of Anesthesiology West China Hospital Sichuan University

Brain damage can cause lung injury. To explore the mechanism underlying the lung injury induced by acute cerebral ischemia(ACI), we established a middle cerebral artery occlusion(MCAO) model in male Sprague-Dawley rats. We focused on glia maturation factor b(GMFB) based on quantitative analysis of the global rat serum *** chain reaction, western blotting, and immunofluorescence revealed that GMFB was overexpressed in astrocytes in the brains of rats subjected to MCAO. We cultured rat primary astrocytes and confirmed that GMFB was also up-regulated in primary astrocytes after oxygen-glucose deprivation(OGD). We subjected the primary astrocytes to Gmfb RNA interference before OGD and collected the conditioned medium(CM) after *** then used the CM to culture pulmonary microvascular endothelial cells(PMVECs) acquired in advance and assessed their status. The viability of the PMVECs improved significantly when Gmfb was blocked. Moreover,ELISA assays revealed an elevation in GMFB concentration in the medium after OGD. Cell cultures containing recombinant GMFB showed increased levels of reactive oxygen species and a deterioration in the state of the *** conclusion, GMFB is up-regulated in astrocytes after ACI, and brain-derived GMFB damages PMVECs by increasing reactive oxygen species. GMFB might thus be an initiator of the lung injury induced by ACI.

关键词： Glial maturation factor b Acute cerebral ischemia Lung injury RNA interference Pulmonary microvascular endothelial cells Reactive oxygen species

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