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The miR-34b-5p-negative target Gnai2 aggravates fluorine combined with aluminum-induced apoptosis of rat offspring hippocampal neurons and NG108-15 cells

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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH 2023年第25期30卷 66822-66839页

作者： zhang, luwen Li, Yang Tao, Dan Yang, Liu zhang, Yue zhang, Hua Xie, Chun Guizhou Med Univ Sch Publ Hlth Key Lab Environm Pollut Monitoring & Dis Control Minist Educ Guiyang 550025 Peoples R China Guizhou Med Univ Sch Basic Med Sci Dept Pharmacol Guiyang 550025 Peoples R China

It is known that fluorine and aluminum are commonly found in the environment and that long-term overexposure can adversely affect the organism's nervous system, damaging the structure and function of brain tissue. Our previous study showed that fluorine combined with aluminum (FA) could trigger apoptosis in vitro and cause spatial learning and memory impairment and differentially expressed miRNAs (including miR-34b-5p) in the hippocampi in vivo. However, the detailed mechanism is unclear. Learning memory damage is implicated in excessive hippocampal neuron apoptosis, and miR-34b-5p participates in regulating the hippocampal neuron apoptosis. Thus, in the current research, Sprague-Dawley (SD) rats were subjected to FA, and NG108-15 control cells and NG108-15 cells pretransfected with miR-34b-5p agomir or antagomir were exposed to FA. We found that FA triggered apoptosis of rat hippocampal neurons and NG108-15 cells, increased miR-34b-5p expression, and decreased Gnai2, PKA, ERK and CREB expression. Inhibition of miR-34b-5p alleviated FA-induced NG108-15 cell apoptosis and further increased Gnai2, PKA, ERK, and CREB expression, and vice versa. Furthermore, miR-34b-5p modulated the level of Gnai2 by directly targeting its 3'-untranslated region (UTR), as verified through the dual Luciferase reporter assay. These outcomes suggested that miR-34b-5p participated in FA-induced neuronal apoptosis by targeting Gnai2 negatively, thereby inhibiting the PKA/ERK/CREB signaling pathway.

关键词： Fluorine Aluminum miR-34b-5p G protein alpha inhibiting activity polypeptide 2 Apoptosis

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Engineering Methyltransferase and Sulfoxide Synthase for High-Yield Production of Ergothioneine

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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022年第1期71卷 671-679页

作者： zhang, luwen Tang, Jiawei Feng, Meiqing Chen, Shaoxin Fudan Univ Dept Biol Med Sch Pharm Shanghai 201203 Peoples R China Fudan Univ Shanghai Engn Res Ctr Immunotherapeut Sch Pharm Shanghai 201203 Peoples R China China State Inst Pharmaceut Ind Shanghai Inst Pharmaceut Ind Shanghai 201203 Peoples R China

Ergothioneine (ERG) is an unusual sulfur-containing amino acid with antioxidant activity that can be synthesized by certain bacteria and fungi. Microbial fermentation is a promising method for ERG production. In this study, the bifunctional enzyme methyltransferase-sulfoxide synthase NcEgt1 from Neurospora crassa was truncated to obtain sulfoxide synthase TNcEgt1, which showed a higher expression level in Escherichia coli BL21(DE3). Then, the genes egtD encoding methyltransferase EgtD and egtE encoding C-S lyase EgtE from Mycobacterium smegmatis were cloned with TncEgt1 into E. coli BL21(DE3) to produce 70 mg/L ERG. To improve ERG production, TNcEgt1 and EgtD were modified, and the resulting mutants were screened with an established high-throughput method which could directly analyze the ERG content in culture broths. After several rounds of mutation and screening, the optimal mutant MD4 was obtained and produced 290 mg/L ERG. Furthermore, a fed-batch culture was conducted in a 5 L bioreactor. After optimizing the fermentation process, the ERG yield reached 5.4 g/L after 94 h of cultivation supplemented with amino acids and glycerol, which is the highest ERG yield reported to date. The results showed that ERG production was significantly improved by modifying the key enzymes, and the engineered strains constructed in this study have potential industrial application prospects.

关键词： ergothioneine E coli metabolic engineering protein engineering fed-batch fermentation

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A common mechanism links Epstein-Barr virus infections and autoimmune diseases

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JOURNAL OF MEDICAL VIROLOGY 2023年第1期95卷 e28363-e28363页

作者： zhang, luwen Univ Nebraska Nebraska Ctr Virol Sch Biol Sci Lincoln NE 68583 USA

Epstein-Barr virus (EBV) infection is associated with a variety of the autoimmune diseases. There is apparently no unified model for the role of EBV in autoimmune diseases. In this article, the development of autoimmune diseases is proposed as a simple two-step process: specific autoimmune initiators may cause irreversible changes to genetic materials that increase autoimmune risks, and autoimmune promoters promote autoimmune disease formation once cells are susceptible to autoimmunity. EBV has several types of latencies including type III latency with higher proliferation potential. EBV could serve as autoimmune initiators for some autoimmune diseases. At the same time, EBV may play a promotional role in majority of the autoimmune diseases by repeated replenishment of EBV type III latency cells and inflammatory cytokine productions in persistent stage. The type III latency cells have enhanced capacity as antigen-presenting cells that would facilitate the development of both B and T cell-mediated autoimmunity. The repeated cytokine productions are achieved by the repeated infection of naive B-lymphocytes and proliferation of type III latency cells that produce inflammatory cytokines. Presentation of viral or self-antigens by EBV type III latency B lymphocytes may promote autoreactive B cell and T cell proliferation, which can be amplified by type III latency cells-mediated cytokines productions. Different autoimmune diseases may require different kinds of pathogenic immune cells and/or specific cytokines. Frequency of the replenishment of EBV type III latency cells may determine the specific effect of the promoter functions. A specific initiator plus EBV-mediated common promoter function may lead to development of a specific autoimmune disease and link EBV-infection to a variety of autoimmunity.

关键词： autoimmune diseases Epstein Barr virus initiator latency lupus multiple sclerosis promoter

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A study on the factors that influence consumers' continuance intention to use artificial intelligence chatbots in a pharmaceutical e-commerce context

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ELECTRONIC LIBRARY 2025年第3期43卷 303-321页

作者： Jia, Jing Chen, Lu zhang, luwen Xiao, Manling Wu, Chengzhen Changzhou Univ Sch Business Changzhou Peoples R China Tsinghua Univ Sch Social Sci Beijing Peoples R China Konkuk Univ Sch Int Coll Seoul South Korea Hanyang Univ Sch Business Seoul South Korea

PurposeThis study aims to explore the antecedent factors affecting consumers' intention to continue using artificial intelligence (AI) chatbots in pharmaceutical e-commerce. This study aims to provide a comprehensive understanding of how technical characteristics and user satisfaction influence continuance intention, offering insights for enhancing AI chatbot systems and customer service ***/methodology/approachThis study adopts both online and offline data collection methods and uses structural equation modelling with AMOS 26.0 to investigate the factors influencing consumers' continuance intention to use AI chatbots in the pharmaceutical e-commerce context. The research model integrates technical characteristics of AI chatbots, service expectation confirmation, emotional satisfaction, cognitive satisfaction and e-health *** results of this study indicate that perceived flexibility, accuracy, reliability and convenience of AI chatbots positively influence service expectation confirmation, while anthropomorphism does not have a significant impact. Both emotional and cognitive satisfaction positively influence consumers' continuance intention. This study highlights the importance of optimizing AI chatbot systems to improve service efficiency and consumer ***/valueThis study uniquely integrates the pharmaceutical e-commerce context into AI chatbots research, addressing an existing gap in context-specific studies. This study introduces a dual-dimensional satisfaction framework encompassing cognitive and emotional satisfaction, offering theoretical support for more holistic satisfaction enhancement strategies. The findings of this study also provide practical implications for companies seeking to establish and sustain long-term, stable customer relationships through advanced AI chatbot systems.

关键词： Continuance intention Cognitive satisfaction Emotional satisfaction AI chatbots E-health literacy Pharmaceutical e-commerce Service expectation confirmation

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A study on the influence of digital literacy on elderly user's intention to identify social media false information

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ELECTRONIC LIBRARY 2024年第5期42卷 701-721页

作者： Chen, Lu Jia, Jing Xiao, Manling Wu, Chengzhen zhang, luwen Changzhou Univ Sch Business Changzhou Peoples R China Konkuk Univ Dept Adv Ind Fus Seoul South Korea Hanyang Univ Sch Business Seoul South Korea Konkuk Univ Dept Adv Ind Fus Seoul South Korea

PurposeThis research exclusively focuses on China's elderly Internet users given how severe a threat disinformation has become for this particular population group as social media platforms thrive and the number of elderly netizens grows in China. The purpose of this study is to explore the mechanism of how elderly social media users' intention to identify false information is influenced helps supplement the knowledge system of false information governance and provides a basis for correction ***/methodology/approachThis study focuses on the digital literacy of elderly social media users and builds a theoretical model of their intention to identify false information based on the theory of planned behaviour. It introduces two variables - namely, risk perception and self-efficacy - and clarifies the relationships between the variables. Questionnaires were distributed both online and offline, with a total of 468 collected. A structural equation model was built for empirical *** results show that digital literacy positively influences risk perception, self-efficacy, subjective norms and perceived behavioural control. Risk perception positively influences subjective norms, perceived behavioural control and the attitude towards the identification of false information. Self-efficacy positively influences perceived behavioural control but does not significantly impact the intention to identify. Subjective norms positively influence the attitude towards identification and the intention to identify. Perceived behavioural control positively influences the attitude towards identification but does not significantly impact the intention to identify. The attitude towards identification positively influences the intention to ***/valueBased on relevant theories and the results of the empirical analysis, this study provides suggestions for false information governance from the perspectives of social media platform collaboration and elderl

关键词： Elderly social media users False information identification Theory of planned behaviour Digital literacy Risk perception Self-efficacy

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Cytoplasmic Shift of Interferon Regulatory Factors Co-Evolved With Jawed Vertebrate Innate Immunity

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JOURNAL OF MEDICAL VIROLOGY 2025年第2期97卷 e70247页

作者： Hubing, Vanessa Marquis, Avery Ziemann, Chanasei Moriyama, Hideaki Moriyama, Etsuko N. zhang, luwen Univ Nebraska Sch Biol Sci Lincoln NE 68588 USA Univ Nebraska Ctr Plant Sci Innovat Lincoln NE 68588 USA Univ Nebraska Nebraska Ctr Virol Lincoln NE 68588 USA

The emergence of jaws in early vertebrates introduced a novel feeding apparatus and powerful oral defenses, but it also increased the risk of physical injury and pathogen exposure. Interferon regulatory factors (IRFs) play critical roles in orchestrating innate immunity and inflammation in response to invading microbes and tissue damage, with their subcellular localization being essential to some IRFs' function. Our results indicate that IRF members underwent independent expansion and diversification in two distinct vertebrate lineages: jawed and jawless vertebrates. The jawed vertebrate-specific factor, IRF5, has maintained conserved nuclear export sequences throughout evolution, while newly diversified IRF members in jawed vertebrates have acquired cytoplasmic localization. This cytoplasmic shift particularly affected IRFs involved in type I interferon (IFN) signaling (IRF3, IRF5, IRF7, and IRF9), suggesting co-evolution with the development of the type I IFN system in jawed animals. Interestingly, although IRF9 is inherently nuclear, its association with Signal Transducer and Activator of Transcription 2 (STAT2) has led to its cytoplasmic localization. Additionally, IRF6, another jawed vertebrate-specific factor, plays a crucial role in jaw development, reflecting an evolutionary adaptation that aligns structural innovations with immune function. Our findings suggest that the evolution of jaws coincided with the adoption of cytoplasmic localization in IRF members, potentially enhancing rapid immune responses to meet the immunological challenges posed by the predatory lifestyle of early jawed vertebrates.

关键词： evolution inflammation innate immunity interferon IRF jaw

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Construction of a hydrogen-bonded organic framework-based therapeutic platform by one-pot method

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CHEMICAL COMMUNICATIONS 2025年第17期61卷 3560-3563页

作者： Wang, Yan Qiao, Jiarui Wei, Wenjing Liu, Meng Wei, Xianhao zhang, luwen Ou, Junhe Jiang, Tingyan Pang, Maolin Guangxi Normal Univ Sch Chem & Pharmaceut Sci Guilin 541001 Peoples R China

The anticancer drug camptothecin (CPT) was successfully in situ loaded into a hydrogen-bonded organic framework (HOF) by one-pot method with a high loading efficiency of 42 wt%. The resultant HOF based therapeutic pla... 详细信息

关键词： Hydrogen bonds

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Epidemiological and Antimicrobial Resistant Patterns, and Molecular Mechanisms of Carbapenem-Resistant Klebsiella pneumoniae Infections in ICU Patients

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INFECTION AND DRUG RESISTANCE 2023年 16卷 2813-2827页

作者： Lu, Fanbo zhang, luwen Ji, Juanjuan Xu, Yuanhong Wang, Bo Xia, Jinxing Anhui Med Univ Affiliated Hosp 1 Dept Clin Lab Hefei Peoples R China Anhui Med Univ Affiliated Hosp 1 Dept Resp & Crit Care Med Hefei Peoples R China Anhui Med Univ Affiliated Hosp 1 Dept Clin Lab 218 Jixi Rd Hefei Anhui Peoples R China

Objective: To study the epidemiological and antimicrobial resistant patterns, clinical characteristics and risk factors of critically ill patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) from intensive care units (ICUs). The potential molecular mechanisms of antimicrobial resistance and virulence of CRKP were investigated through evaluation of associated ***: Totally, 201 ICU patients infected with K. pneumoniae were recruited from January 2020 through January 2021. K. pneumoniae strains were collected from diverse clinical specimens and identified by microbial cultures and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Antimicrobial resistance was measured through broth micro-dilution or Kirby- Bauer assays. The carbapenemase-, virulence-, and capsular serotype-associated genes of CRKP were individually detected by PCR and sequencing. Demographic and clinical profiles were acquired from hospital databases to evaluate the correlation of CRKP infection incidence with clinical risk ***: Of the 201 K. pneumoniae strains, CRKP accounted for 41.29%. Seasonal bias existed in local prevalence of CRKP infections. CRKP strains mounted significantly strong resistance against major antimicrobial agents except ceftazidime-avibactam, tigecycline and minocycline. Recent exposure to certain antibiotics and prior treatment with invasive interventions were prone to increase CRKP infection risks with worsened infectious outcomes. The local top carbapenemase-encoding and virulence-associated genes of CRKP were blaKPC and irp2, respectively. Nearly half of CRKP isolates harbored a capsular polysaccharide serotype of K14. K64 (wzi-64) which preferentially emerged in the cohort with worse outcomes of ***: Featured epidemiology and typical clinical characteristics existed extensively in K. pneumoniae infections among ICU patients. The CRKP cohort exhibited substantially high antimicrobial resista

关键词： carbapenem-resistantKlebsiella pneumoniae epidemiology clinical features antimicrobial resistance virulence ICU

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Joint Multiscale Cross-Lingual Speaking Style Transfer With Bidirectional Attention Mechanism for Automatic Dubbing

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IEEE-ACM TRANSACTIONS ON AUDIO SPEECH AND LANGUAGE PROCESSING 2024年 32卷 517-528页

作者： Li, Jingbei Li, Sipan Chen, Ping zhang, luwen Meng, Yi Wu, Zhiyong Meng, Helen Tian, Qiao Wang, Yuping Wang, Yuxuan Tsinghua Univ Shenzhen Int Grad Sch Tsinghua CUHK Joint Res Ctr Media Sci Technol & Sy Shenzhen 518055 Peoples R China Chinese Univ Hong Kong Dept Syst Engn & Engn Management Hong Kong Peoples R China ByteDance Shanghai 201100 Peoples R China

Automatic dubbing, which generates a corresponding version of the input speech in another language, can be widely utilized in many real-world scenarios, such as video and game localization. In addition to synthesizing the translated scripts, automatic dubbing further transfers the speaking style in the original language to the dubbed speeches to give audiences the impression that the characters are speaking in their native tongue. However, state-of-the-art automatic dubbing systems only model the transfer on the duration and speaking rate, disregarding the other aspects of speaking style, such as emotion, intonation and emphasis, which are also crucial to fully understand the characters and speech. In this paper, we propose a joint multiscale cross-lingual speaking style transfer framework to simultaneously model the bidirectional speaking style transfer between two languages at both the global scale (i.e., utterance level) and local scale (i.e., word level). The global and local speaking styles in each language are extracted and utilized to predict the global and local speaking styles in the other language with an encoder-decoder framework for each direction and a shared bidirectional attention mechanism for both directions. A multiscale speaking style-enhanced FastSpeech 2 is then utilized to synthesize the desired speech with the predicted global and local speaking styles for each language. The experimental results demonstrate the effectiveness of our proposed framework, which outperforms a baseline with only duration transfer in objective and subjective evaluations.

关键词： Automatic dubbing cross-lingual speaking style transfer multiscale speaking style transfer bidirectional attention mechanism text-to-speech synthesis

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AMSA-CAFF Net: Counting and high-quality density map estimation from X-ray images of electronic components

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EXPERT SYSTEMS WITH APPLICATIONS 2024年第PartC期237卷

作者： zhang, Zhiguo zhang, luwen zhang, Huan Guo, Yimo Wang, Haixia Lu, Xiao Shandong Univ Sci & Technol Coll Elect Engn & Automat Qingdao 266590 Peoples R China Shandong Univ Sci & Technol Coll Energy Storage Technol Qingdao 266590 Peoples R China

Accurately estimating object numbers plays a crucial role in industrial applications. However, object counting in computer vision poses a formidable challenge, particularly when dealing with images containing tiny, similar, and stacked objects. Therefore, this paper proposes an encoder-decoder-based convolutional neural network named AMSA-CAFF Net to accurately count and regress high-quality density maps from X-ray images of highly dense microscopic components. AMSA-CAFF Net has three major components: an adaptive multi-scale feature aggregation (AMSA) module for encoding adaptive multi-scale features in the encoder, a channel-wise adaptive feature fusion (CAFF) module to ensure smooth feature fusion, and a continuous feature enhancement mechanism to promote information integration in the decoder. In addition, there is still a lack of datasets dedicated to industrial object counting tasks. To address the limitations associated with the existing datasets, we construct a novel and large-scale object counting dataset named X-ray-based industrial electronic component counting dataset (XRAY-IECCD), consisting of 1,460 X-ray images of 10 types of components, resulting in a total of 2,915,126 objects annotated with points. To the best of our knowledge, the XRAY-IECCD is the first dataset of tiny, dense, multi-class object counts with a substantial number of annotations. We evaluate the performance of AMSA-CAFF Net on three datasets: the XRAY-IECCD, crowd counting benchmark ShanghaiTech dataset, and object counting benchmark CARPK dataset. The proposed framework outperforms the state-of-the-art approaches over the proposed XRAY-IECCD and CARPK datasets, highlighting its effectiveness. Furthermore, we achieve competitive results on the ShanghaiTech dataset, which demonstrates the generalization capability of our method.

关键词： Electronic component counting High-quality density map estimation Industrial automation

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