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The cluster digging behavior of larvae confers trophic benefits to fitness in insects

Insect Science 2024年第3期31卷 870-884页

作者： Yujie Wu Qiang Wang Weikang Yang Sheng Zhang Chuan-Xi Mao Nana He Shaojie Zhou Chuanming Zhou Wei Liu School of Plant Protection Anhui Agricultural UniversityAnhui Province Key Laboratory of Crop Integrated Pest ManagementAnhui Province Engineering Laboratory for Green Pesticide Development and ApplicationHefeiChina College of Plant Protection Nanjing Agricultural UniversityNanjingChina School of Teacher Education Nanjng Xiaozhuang UniversityNanjingChina State Key laboratory of Biocatalysis and Enzyme engineering Hubei Province Key Laboratory of Biotechnology of Chinese Traditional MedicineNational&Local Joint Engineering Research Center of High-throughput Drug Screening TechnologySchool of Life ScienceHubei UniversityWuhanChina

Collective behaviors efficiently impart benefits to a diversity of species ranging from bacteria to *** larvae tend to cluster and form coordinated digging groups under crowded conditions,yet understanding the rules governing this behavior is in its *** primarily took advantage of the Drosophila model to investigate cooperative foraging ***,we report that Drosophila-related species and the black soldier fly have evolved a conserved strategy of cluster digging in food ***,we investigated relative factors,including larval stage,population density,and food stiffness and quality,that affect the cluster digging ***,oxygen supply through the posterior breathing spiracles is necessary for the organization of digging *** importantly,we theoretically devise a mathematical model to accurately calculate how the cluster digging behavior expands food resources by diving depth,cross-section area,and food *** found that cluster digging behavior approximately increases 2.2 fold depth,1.7-fold cross-section area,and 1.9 fold volume than control groups,*** of food sources significantly facilitates survival,larval development,and reproductive success of Drosophila challenged with competition for limited food resources,thereby conferring trophic benefits to fitness in ***,our findings highlight that the cluster digging behavior is a pivotal behavior for their adaptation to food scarcity,advancing a better understanding of how this cooperative behavior confers fitness benefits in the animal kingdom.

关键词： cluster digging determinant development fecundity larvae mathematical model

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Anti-epileptic and Neuroprotective Effects of Ultra-low Dose NADPH Oxidase Inhibitor Dextromethorphan on Kainic Acid-induced Chronic Temporal Lobe Epilepsy in Rats

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Neuroscience Bulletin 2024年第5期40卷 577-593页

作者： Jing-Jing Yang Ying-Xin Liu Yan-Fang Wang Bi-Ying Ge Ying Wang Qing-Shan Wang Sheng Li Jian-Jie Zhang Ling-Ling Jin Jau-Shyong Hong Sheng-Ming Yin Jie Zhao College of Basic Medical Sciences Dalian Medical UniversityDalian116044China Department of Neurology The First Affiliated Hospital of Dalian Medical UniversityDalian116011China national and local joint engineering Research Center for drug Research and development of Neurodegenerative Diseases Dalian116044China School of Public Health Dalian Medical UniversityDalian116044China Neurobiology laboratory National Institute of Environmental Health SciencesNational Institutes of HealthResearch Triangle ParkDurhamNC27709USA

Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy(TLE).We postulated that kainic acid(KA)-Induced status epilepticus triggers microglia-dependent inflammation,leading to neuronal damage,a lowered seizure threshold,and the emergence of spontaneous recurrent seizures(SRS).Extensive evidence from our laboratory suggests that dextromethorphan(DM),even in ultra-low doses,has anti-inflammatory and neuroprotective effects in many animal models of neurodegenerative *** results showed that administration of DM(10 ng/kg per day;subcutaneously via osmotic minipump for 4 weeks)significantly mitigated the residual effects of KA,including the frequency of SRS and seizure *** addition,DM-treated rats showed improved cognitive function and reduced hippocampal neuronal *** found suppressed microglial activation-mediated neuroinflammation and decreased expression of hippocampal gp91^(phox) and p47^(phox) proteins in KA-induced chronic TLE ***,even after discontinuation of DM treatment,ultra-low doses of DM continued to confer long-term anti-seizure and neuroprotective effects,which were attributed to the inhibition of microglial NADPH oxidase 2 as revealed by mechanistic studies.

关键词： Temporal lobe epilepsy Dextromethorphan NADPH oxidase Ultra-low dose

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Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1

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Science China(Life Sciences) 2024年第6期67卷 1212-1225页

作者： Zhijie Hu Mengxia Li Yufeng Chen Liutao Chen Yuting Han Chengyong Chen Xin Lu Nan You Yawen Lou Yingye Huang Zhanfeng Huo Chao Liu Cheng Liang Susu Liu Ke Deng Liangfu Chen Shangwu Chen Guohui Wan Xiaojian Wu Yonggui Fu Anlong Xu State Key laboratory of Biocontrol Guangdong Province Key Laboratory of Pharmaceutical Functional GenesDepartment of BiochemistrySchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China Department of General Surgery(Colorectal Surgery)&Guangdong Provincial Key laboratory of Colorectal and Pelvic Floor Diseases&Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China national-local joint engineering laboratory of druggability and New drug Evaluation National Engineering Research Center for New Drug and Druggability(cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China

Generally shortened 3′UTR due to alternative polyadenylation(APA)is widely observed in cancer,but its regulation mechanisms for cancer are not well ***,with profiling of APA in colorectal cancer tissues and poly(A)signal editing,we firstly identified that the shortened 3′UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and *** found that liquid-liquid phase separation(LLPS)of PABPN1 is reduced albeit with higher expression in cancer,and the reduction of LLPS leads to the shortened 3′UTR of CTNNBIP1and promotes cell proliferation and ***,the splicing factor SNRPD2 upregulated in colorectal cancer,can interact with glutamic-proline(EP)domain of PABPN1,and then disrupt LLPS of PABPN1,which attenuates the repression effect of PABPN1 on the proximal poly(A)*** results firstly reveal a new regulation mechanism of APA by disruption of LLPS of PABPN1,suggesting that regulation of APA by interfering LLPS of 3′end processing factor may have the potential as a new way for the treatment of cancer.

关键词： alternative polyadenylation colorectal cancer CTNNBIP1 PABPN1 liquid-liquid phase separation SNRPD2

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Effective protective agents against the organ toxicity of T-2 toxin and corresponding detoxification mechanisms: A narrative review

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animal Nutrition 2024年第1期16卷 251-266页

作者： Pengju Wang Lv-hui Sun Xu Wang Qinghua Wu Aimei Liu Hubei Key laboratory of Diabetes and Angiopathy Medicine Research Institute Xianning Medical College Hubei University of Science and Technology Hubei Hongshan laboratory College of Animal Science and Technology Huazhong Agricultural University national Reference laboratory of Veterinary drug Residues (HZAU) and MAO Key laboratory for Detection of Veterinary drug Residues Huazhong Agricultural University College of Life Science Yangtze University

T-2 toxin is one of the most widespread and toxic fungal toxins in food and feed. It can cause gastrointestinal toxicity, hepatotoxicity, immunotoxicity, reproductive toxicity, neurotoxicity, and nephrotoxicity in humans and animals. T-2 toxin is physicochemically stable and does not readily degrade during food and feed processing. Therefore, suppressing T-2 toxin-induced organ toxicity through antidotes is an urgent issue. Protective agents against the organ toxicity of T-2 toxin have been recorded widely in the literature, but these protective agents and their molecular mechanisms of detoxification have not been comprehensively summarized. In this review, we provide an overview of the various protective agents to T-2 toxin and the molecular mechanisms underlying the detoxification effects. Targeting appropriate targets to antagonize T-2 toxin toxicity is also an important option. This review will provide essential guidance and strategies for the better application and development of T-2 toxin antidotes specific for organ toxicity in the future.

关键词： T-2 toxin Organ toxicity Protective agent Detoxification mechanism

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Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinib

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Acta Pharmaceutica Sinica B 2024年第2期14卷 517-532页

作者： Shuang Xiang Xiaoyun Lu International Cooperative laboratory of Traditional Chinese Medicine Modernization and Innovative drug Discovery of Chinese Ministry of Education(MOE) Guangdong Provincial Key Laboratory of New Drug Design and EvaluationGuangzhou City Key Laboratory of Precision Chemical Drug DevelopmentSchool of PharmacyJinan UniversityGuangzhou 510632China

Neurotrophic receptor kinase(NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors,and tropomyosin receptor kinase(TRK) has been considered as an attractive therapeutic target for "pan-cancer" harboring these ***,two generations TRK inhibitors have been *** representative second-generation inhibitors selitrectinib and repotrectinib were designed to overcome clinic acquired resistance of the first-generation inhibitors larotrectinib or entrectinib resulted from solvent-front and gatekeeper on-target ***,xDFG(TRKAG667C/A/S,homologous TRKCG696C/A/S) and some double mutations still confer resistance to selitrectinib and repotrectinib,and overcoming these resistances represents a major unmet clinical *** this review,we summarize the acquired resistance mechanism of the first-and second-generation TRK inhibitors,and firstly put forward the emerging selective type Ⅱ TRK inhibitors to overcome xDFG mutations mediated ***,we concluded our perspectives on new challenges and future directions in this field.

关键词： NTRK fusions TRK kinase Clinical resistance xDFG mutations Selective type II inhibitors

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A nanoplatform with oxygen self-supplying and heat-sensitizing capabilities enhances the efficacy of photodynamic therapy in eradicating multidrug-resistant biofilms

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Journal of Materials Science & Technology 2024年第2期169卷 209-219页

作者： Haixin Zhang Yi Zou Kunyan Lu Yan Wu Yuancheng Lin Jingjing Cheng Chunxia Liu Hong Chen Yanxia Zhang Qian Yu State and local joint engineering laboratory for Novel Functional Polymeric Materials College of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou 215123China Department of Cardiovascular Surgery of the First Affiliated Hospital and Institute for Cardiovascular Science Suzhou Medical College of Soochow UniversitySoochow UniversitySuzhou 215007China

Bacterial biofilms,especially those caused by multidrug-resistant bacteria,have emerged as one of the greatest dangers to global public *** acceleration of antimicrobial resistance to conventional an-tibiotics and the severe lack of new drugs necessitates the development of novel agents for biofilm *** therapy(PDT)is a promising non-antibiotic method for treating bacterial ***,its application in biofilm eradication is hampered by the hypoxic microenvironment of biofilms and the physical protection of extracellular polymeric *** this study,we develop a composite nanoplatform with oxygen(O_(2))self-supplying and heat-sensitizing capabilities to improve the PDT efficacy against ***_(2)/ICG@PDA nanoparticles(CIP NPs)are fabricated by combining calcium peroxide(CaO_(2))with the photosensitizer indocyanine green(ICG)via electrostatic interactions,followed by coating with polydopamine(PDA).The CIP NPs can gradually generate O_(2)in response to the acidic microenvironment of the biofilm,thereby alleviating its hypoxic *** near-infrared(NIR)irradiation,the nanoplatform converts O_(2)into a significant amount of singlet oxygen(^(1)O_(2))and heat to eradicate *** generated heat enhances the release of O_(2),accelerates the generation of^(1)O_(2)in PDT,increases cell membrane permeability,and increases bacterial sensitivity to^(1)O_(2).This nanoplatform significantly improves the efficacy of PDT in eradicating biofilm-dwelling bacteria without fostering drug *** on biofilm eradication demonstrate that this nanoplatform can eradicate over 99.9999%of methicillin-resistant Staphylococcus aureus(MRSA)biofilms under 5-min NIR ***,these integrated advantages enable the system to promote the healing of MRSA biofilm-infected wounds with negligible toxicity in vivo,indicating great promise for overcoming the obstacles associated with bacterial biofilm eradication.

关键词： Bacterial biofilm Multidrug-resistant bacteria Photodynamic therapy Oxygen supplying Photothermal therapy

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Core and variable antimicrobial resistance genes in the gut microbiomes of Chinese and European pigs

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Zoological Research 2024年第1期45卷 189-200页

作者： Cui-Hong Tong Zhi-Peng Huo Lu Diao Dan-Yu Xiao Ruo-Nan Zhao Zhen-Ling Zeng Wen-Guang Xiong Guangdong Provincial Key laboratory of Veterinary Pharmaceutics development and Safety Evaluation South China Agricultural UniversityGuangzhouGuangdong 510642China national Risk Assessment laboratory for Antimicrobial Resistance of animal Original Bacteria College of Veterinary MedicineSouth China Agricultural UniversityGuangzhouGuangdong 510642China national laboratory of Safety Evaluation(Environmental Assessment)of Veterinary drugs South China Agricultural UniversityGuangzhouGuangdong 510642China national Reference laboratory of Veterinary drug Residues South China Agricultural UniversityGuangzhouGuangdong 510642China

Monitoring the prevalence of antimicrobial resistance genes(ARGs)is vital for addressing the global crisis of antibiotic-resistant bacterial *** its importance,the characterization of ARGs and microbiome structures,as well as the identification of indicators for routine ARG monitoring in pig farms,are still lacking,particularly concerning variations in antimicrobial exposure in different countries or ***,metagenomics and random forest machine learning were used to elucidate the ARG profiles,microbiome structures,and ARG contamination indicators in pig manure under different antimicrobial pressures between China and *** showed that Chinese pigs exposed to high-level antimicrobials exhibited higher total and plasmid-mediated ARG abundances compared to those in European pigs(P<0.05).ANT(6)-Ib,APH(3')-IIIa,and tet(40)were identified as shared core ARGs between the two pig ***,the core ARGs identified in pig populations were correlated with those found in human populations within the same geographical *** and Prevotella were identified as the dominant genera in the core microbiomes of Chinese and European pigs,*** ARG markers and 43 biomarkers were able to differentiate between the Chinese and European pig manure samples with accuracies of 100%and 98.7%,*** for assessing ARG contamination in Chinese and European pigs also achieved high accuracy(r=0.72-0.88).Escherichia flexneri in both Chinese and European pig populations carried between 21 and 37 *** results of this study emphasize the importance of global collaboration in reducing antimicrobial resistance risk and provide validated indicators for evaluating the risk of ARG contamination in pig farms.

关键词： Metagenomic Pig manure Antimicrobial pressure Antimicrobial resistance genes Microbiome

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Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity

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Acta Pharmaceutica Sinica B 2024年第1期14卷 350-364页

作者： Yongshun Zhang Lan Yang Yangsen Ou Rui Hu Guangsheng Du Shuang Luo Fuhua Wu Hairui Wang Zhiqiang Xie Yu Zhang Chunting He Cheng Ma Tao Gong Ling Zhang Zhirong Zhang Xun Sun Key laboratory of drug-Targeting and drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China Med-X Center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10(PTEN)gene in cancer cells may be associated with immunosuppressive tumor microenvironment(TME)and poor response to immune checkpoint blockade(ICB)***,efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB ***,we screened an adeno-associated virus(AAV)capsid for efficient PTEN gene delivery into B16F10 tumor *** demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death(ICD)and increasing immune cell ***,we developed an anti-PD-1 loaded phospholipid-based phase separation gel(PPSG),which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in *** order to effectively inhibit the recurrence of melanoma,we further applied a triple therapy based on AAV6-PTEN,PPSG^(@anti-PD-1)and CpG,and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory,which completely rejected tumor *** anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

关键词： Triple therapy Adeno-associated virus PTEN PPSG@anti-PD-1 CpG Immunogenic cell death Antitumor immune response Immune memory

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A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3232-3250页

作者： Ping Yu Tanwei Gu Yueyang Rao Weimin Liang Xi Zhang Huanguo Jiang Jindi Lu Jianglian She Jianmin Guo Wei Yang Yonghong Liu Yingfeng Tu Lan Tang Xuefeng Zhou Guangdong Provincial Key laboratory of New drug Screening Guangdong-Hong Kong-Macao Joint Laboratory for New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China CAS Key laboratory of Tropical Marine Bio-Resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaSouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China NMPA Key laboratory for Research and Evaluation of drug Metabolism School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Guangdong Lewwin Pharmaceutical Research Institute Co. Ltd.Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and ResearchGuangdong Engineering Research Center for Innovative Drug Evaluation and ResearchGuangzhou 510990China

Insufficient therapeutic strategies for acute kidney injury(AKI)necessitate precision therapy targeting its *** study reveals the new mechanism of the marine-derived anti-AKI agent,piericidin glycoside S14,targeting peroxiredoxin 1(PRDX1).By binding to Cys83 of PRDX1 and augmenting its peroxidase activity,S14 alleviates kidney injury efficiently in Prdx1-overexpression(Prdx1-OE)***,S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS *** to the limited druggability of S14 with low bioavailability(2.6%)and poor renal distribution,a pH-sensitive kidney-targeting dodecanaminechitosan nanoparticle system is constructed to load S14 for precise treatment of AKI.L-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1(Kim-1)-overexpressed *** developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 *** encapsulation with micelles,the AUC_(0-t),half-life time,and renal distribution of S14 increase 2.5-,1.8-,and 3.1-fold,*** main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDPglycosyltransferase(UGT)-mediated *** summary,this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology,thereby driving advancements in marine drug development for AKI.

关键词： Acute kidney injury Piericidin glycoside Peroxiredoxin 1 Nanodrug Kim-1 targeted ADME Marine drug druggability

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Biological factors driving colorectal cancer metastasis

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 259-272页

作者： Shuai-Xing An Zhao-Jin Yu Chen Fu Min-Jie Wei Long-Hai Shen Department of Pharmacology School of PharmacyChina Medical UniversityShenyang 110122Liaoning ProvinceChina Liaoning Key laboratory of Molecular Targeted Antitumor drug development and Evaluation Liaoning Cancer Immune Peptide Drug Engineering Technology Research CenterKey Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors(China Medical University)Ministry of EducationShenyang 110122Liaoning ProvinceChina BD Department Greenpine Pharma Group Co.LtdTianjin 300020China Center of Oncology Genertec Liaoyou Gem Flower HospitalPanJin 124010Liaoning ProvinceChina

Approximately 20%of colorectal cancer(CRC)patients present with metastasis at *** Stage I-III CRC patients who undergo surgical resection,18%typically suffer from distal metastasis within the first three years following initial *** median survival duration after the diagnosis of metastatic CRC(mCRC)is only 9 *** is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue,allowing cancer cells to spread from primary to distant organs;however,increa-sing evidence suggests that the mCRC process can begin early in tumor *** patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological *** genomic and nongenomic events can induce subclone diversity,which leads to cancer and *** the course of mCRC,metastatic cascades are associated with invasive cancer cell migration through the circulatory system,extravasation,distal seeding,dormancy,and reactivation,with each step requiring specific molecular ***,cancer cells presenting neoantigens can be recognized and eliminated by the immune *** this review,we explain the biological factors that drive CRC metastasis,namely,genomic instability,epigenetic instability,the metastatic cascade,the cancer-immunity cycle,and external lifestyle *** remarkable progress in CRC research,the role of molecular classification in therapeutic intervention remains *** review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.

关键词： cancer Metastasis cascade Cancer immunity Genomic variation Epigenetic instability Lifestyle factor

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