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5S-Heudelotinone alleviates experimental colitis by shaping the immune system and enhancing the intestinal barrier in a gut microbiota-dependent manner

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2153-2176页

作者： qing Meng Jianshuang Guo Ke Lv Yang Liu Jin Zhang Mingyue Li Xirui Cheng Shenghua Chen Xiaoguang Huo quan Zhang Yue Chen Jing Li State Key Laboratory of Medicinal Chemical Biology College of PharmacyNankai UniversityTianjin 300353China College of Chemistry and Frontiers Science Center for New Organic Matter Haihe Laboratory of Sustainable Chemical TransformationsNankai UniversityTianjin 300071China Accendatech Company Ltd.Tianjin 300193China

Aberrant changes in the gut microbiota are implicated in many diseases,including inflammatory bowel disease(IBD).Gut microbes produce diverse metabolites that can shape the immune system and impact the intestinal barrier integrity,indicating that microbe-mediated modulation may be a promising strategy for preventing and treating *** fecal microbiota transplantation and probiotic supplementation are well-established IBD therapies,novel chemical agents that are safe and exert strong effects on the gut microbiota are urgently ***,we report the total synthesis of heudelotinone and the discovery of 5S-heudelotinone(an enantiomer)as a potent agent against experimental colitis that acts by modulating the gut microbiota.5S-Heudelotinone alters the diversity and composition of the gut microbiota and increases the concentration of short-chain fatty acids(SCFAs);thus,it regulates the intestinal immune system by reducing proinflammatory immune cell numbers,and maintains intestinal mucosal integrity by modulating tight junctions(TJs).Moreover,5S-heudelotinone(2.ameliorates colitis-associated colorectal cancer(CAC)in an azoxymethane(AOM)/dextran sulfate sodium(DSS)-induced in situ carcinoma ***,these findings reveal the potential of a novel natural product,namely,5S-heudelotinone,to control intestinal inflammation and highlight that this product is a safe and effective candidate for the treatment of IBD and CAC.

关键词： 5S-heudelotinone Total synthesis Inflammatory bowel disease Gut microbiota Short-chain fatty acids Immune system Intestinal barrier Drug discovery

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Molecular docking-aided AIEgen design: concept, synthesis and applications

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Science China Chemistry 2024年第8期67卷 2614-2628页

作者： Jian-qing Zhang Xiao-Yu Xu Fu-Sheng Liu Shu-Qiang Cao Yu-Xin Gui Yi-Wen Su Xiao-Yu He Ji-Yuan Liang You-quan Zou Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of EducationWuhan UniversityWuhan 430071China Tai Kang Center for Life and Medical Sciences Wuhan UniversityWuhan 430071China Department of Hepatobiliary Pancreatic SurgeryZhongnan Hospital of Wuhan UniversityWuhan 430071China

Aggregate-induced emission luminogens(AIEgens) have been widely used in biological imaging, chemical sensing, and disease treatments. The rational design and construction of AIEgens have received considerable research interests during the last few years. Herein, molecular docking-aided AIEgen design has been reasonably proposed and AIEgen TBQZY with excellent ~1O_(2. generation ability has been synthesized. The newly developed TBQZY could efficiently kill S. epidermidis and methicillinresistant S. epidermidis(MRSE) by tightly binding to bacteria and triggering the accumulation of ~1O_(2. in bacteria. TBQZY specifically regulated the immune system and polarized macrophages from M1 to M2.to accelerate the elimination of biofilm in vivo. In addition, healing acceleration was observed in chronic wounds treated with TBQZY, and side effects were ***, TBQZY had extraordinary potential for combating drug-resistant bacteria in the clinical setting. This research not only provided new concepts for the design of AIEgens, but also shed some lights on the discovery of drugs against drug-resistant bacteria.

关键词： AIEgen molecular docking drug-resistant bacteria biofilm chronic wounds healing

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Prediction model establishment and validation for enteral nutrition aspiration during hospitalization in patients with acute pancreatitis

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World Journal of Gastrointestinal Surgery 2024年第8期16卷 2583-2591页

作者： Ping Hou Hao-Jun Wu Tang Li Jia-Bin Liu quan-qing Zhao Hong-Jiang Zhao Zi-Ming Liu Division II of General Surgery West China Hospital-Chengdu Shangjin NanfuWest China HospitalSichuan UniversityChengdu 611730Sichuan ProvinceChina Division of Biliary Tract Surgery West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Hepatobiliary and Pancreatic Surgery West China Hospital-Chengdu Shangjin NanfuWest China HospitalSichuan UniversityChengdu 611730Sichuan ProvinceChina Department of Thyroid Surgery West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Oncology West China Hospital-Chengdu Shangjin NanfuWest China HospitalSichuan UniversityChengdu 611730Sichuan ProvinceChina Division of Biliary Tract Surgery Department of General SurgeryWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina

BACKGROUND Acute pancreatitis(AP)is a disease caused by abnormal activation of pancreatic enzymes and can lead to self-digestion of pancreatic tissues and dysfunction of other *** nutrition plays a vital role in the treatment of AP because it can meet the nutritional needs of patients,promote the recovery of intestinal function,and maintain the barrier and immune functions of the ***,the risk of aspiration during enteral nutrition is high;once aspiration occurs,it may cause serious complications,such as aspiration pneumonia,and suffocation,posing a threat to the patient’s *** study aims to establish and validate a prediction model for enteral nutrition aspiration during hospitalization in patients with *** To establish and validate a predictive model for enteral nutrition aspiration during hospitalization in patients with *** A retrospective review was conducted on 2.0 patients with AP admitted to Chengdu Shangjin Nanfu Hospital,West China Hospital of Sichuan University from January 2.2. to February *** data were collected from the electronic medical record *** were randomly divided into a validation group(n=40)and a modeling group(n=160)in a 1:4 ratio,matched with 2.0 patients from the same time *** modeling group was further categorized into an aspiration group(n=2.)and a non-aspiration group(n=175)based on the occurrence of enteral nutrition aspiration during *** and multivariate logistic regression analyses were performed to identify factors influencing enteral nutrition aspiration in patients with AP during hospitalization.A prediction model for enteral nutrition aspiration during hospitalization was constructed,and calibration curves were used for *** operating characteristic curve analysis was conducted to evaluate the predictive value of the *** There was no statistically significant difference in general data between the validation and mode

关键词： Acute pancreatitis Hospitalization Enteral nutrition Predictive model Aspiration

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The association and underlying mechanism of the digit ratio(2.:4D)in hypospadias

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Asian Journal of Andrology 2024年第4期26卷 356-365页

作者： Yu Ding Zu-quan Chen Wen-Feng Pan Hao-Jie Chen Min Wu Yi-qing Lyu Hua Xie Yi-Chen Huang Zhong-Zhong Chen Fang Chen Department of Urology Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China Urogenital Development Research Center Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China Clinical Research Center for Hypospadias Pediatric CollegeShanghai Jiao Tong University School of MedicineShanghai 200062China.

The second-to-fourth digit(2.:4D)ratio is thought to be associated with prenatal androgen ***,the relationship between the 2.:4D ratio and hypospadias is poorly understood,and its molecular mechanism is not *** this study,by analyzing the hand digit length of 142.boys with hypospadias(2. distal,68 middle,and 51 proximal)and 196 controls enrolled in Shanghai Children’s Hospital(Shanghai,China)from December 2.2. to December 2.2.,we found that the 2.:4D ratio was significantly increased in boys with hypospadias(P2.Smad2.,and Smad3;mitochondrial function-related genes in cartilage such as AMP-activated protein kinase(AMPK)and nuclear respiratory factor 1(Nrf-1);and vascular development-related genes such as myosin light chain(MLC),notch receptor 3(Notch3),and sphingosine kinase 1(Sphk1),are responsible for the limitation of 4D growth,which results in a higher 2.:4D ratio in boys with hypospadias via decreased endochondral *** study indicates that the ratio of 2.:4D is a risk marker of hypospadias and provides a potential molecular mechanism.

关键词： androgen receptor digit ratio(2.:4D) endochondral ossification hypospadias testosterone level

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A lithium–tin fluoride anode enabled by ionic/electronic conductive paths for garnet-based solid-state lithium metal batteries

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Rare Metals 2024年第2期43卷 575-587页

作者： Lei Zhang Qian-Kun Meng Xiang-Ping Feng Ming Shen Yu-qing Zhang quan-Chao Zhuang Run-Guo Zheng Zhi-Yuan Wang Yan-Hua Cui Hong-Yu Sun Yan-Guo Liu School of Materials Science and Engineering Northeastern UniversityShenyang110819China School of Resources and Materials Northeastern University at QinhuangdaoQinhuangdao066004China School of Materials and Physics China University of Mining&TechnologyXuzhou221116China Institute of Electronic Engineering China Academy of Engineering PhysicsMianyang621900China

The high energy density and stability of solid-state lithium metal batteries(SSLMBs)have garnered great ***-type oxides,especially Li_(6.4)La_(3)Zr_(1.4)Ta_(0.6)O_(12.(LLZTO),with high ionic conductivity,wide electrochemical window,and stability to Li metal anode,are promising solid-state electrolyte(SSEs)materials for ***,Li/LLZTO interface issues including high interface resistance,inhomogeneous Li deposition,and Li dendrite growth have hindered the practical application of ***,a multi-functional Li–SnF_(2. composite anode with Li,LiF,and Li-Sn alloy was specifically designed and *** composite anode improves the wettability to LLZTO,constructing an intimate contact interface between it and ***,ionic/electronic conductive paths in situ formed at the interface can effectively uniform Li deposition and suppress Li *** solid-state symmetric cell exhibits low interface resistance(11Ω·cm^(2.) and high critical current density(1.3 mA·cm^(−2.)at 2.℃.The full SSLMB based on LiFePO_(4) or LiNi_(0.5)Co_(0.2.Mn_(0.3)O_(2. cathode also shows stable cycling performance and high rate *** work provides a new composite anode strategy for achieving high-energy density and high-safety SSLMBs.

关键词： Solid-state lithium metal batteries(SSLMBs) Lithium-tin fluoride anode Ionic/electronic conductive Interface resistance Lithium dendrite

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Overexpression of TRPV1 activates autophagy in human lens epithelial cells under hyperosmotic stress through Ca^(2.)-dependent AMPK/mTOR pathway

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 420-434页

作者： Liu-Hui Huang Jiao Lyu Sheng Chen Ting-Yi Liang Yu-qing Rao Ping Fei Jing Li Hai-Ying Jin Pei-quan Zhao Department of Ophthalmology Shanghai Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Ophthalmology Shanghai Tenth People’s Hospital Affiliated with Shanghai Tongji University School of MedicineShanghai 200072China Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVictoria 3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVictoria 3002Australia Shenzhen Eye Hospital Shenzhen Key Laboratory of OphthalmologyAffiliated Shenzhen Eye Hospital of Jinan UniversityShenzhen 518040Guangdong ProvinceChina Department of Ophthalmology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China

●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 2.0,300,400,500,or 600 mOsm for 6,12.18,2.h in *** chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein *** transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy *** electron microscopy was used to detect the existence of *** interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related *** cytometry was employed to test the apoptosis and intracellular Ca^(2.)*** membrane potential was measured by JC-1 *** cell counting kit-8 assay was used to calculate the cellular *** wound healing assay was used to evaluate the wound closure *** 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in *** 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression *** Ca^(2.)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early *** on this evidence,autophagy activation through the Ca^(2.)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic *** stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration *** of autophagy by ATG7 knockdown had sim

关键词： cataract posterior capsular opacification lens epithelial cell hyperosmotic stress autophagy apoptosis transient receptor potential vanilloid 1

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Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma:A case report

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World Journal of Clinical Cases 2024年第15期12卷 2649-2654页

作者： Xin-Xin Luo Yu-Xuan Du Qi-qing Zhang Lin Zhang Shu-Ying Zeng Zhi-Hong Yu Peng Shen Zheng-quan Feng The Second School of Clinical Medicine Zhejiang Chinese Medical UniversityHangzhou310053Zhejiang ProvinceChina Department of Oncology Tongde Hospital of Zhejiang ProvinceHangzhou 310012Zhejiang ProvinceChina Department of Medical Oncology The First Affiliated HospitalMedical College of Zhejiang UniversityHangzhou 310003Zhejiang ProvinceChina

BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same *** MPCs are rarer than solitary cancers or metachronous *** diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these *** SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory *** multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 2.2.mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were *** on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 ***,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained *** Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.

关键词： Synchronous multiple primary carcinoma Esophageal squamous cell carcinoma Colon adenocarcinoma Cetuximab Chemotherapy Case report

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Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency

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Journal of Integrative Medicine 2024年第1期22卷 72-82页

作者： Jing-shun Meng Yun He Heng-bin Yang Li-ping Zhou Si-yuan Wang Xi-lin Feng Omar Yahya Al-shargi Xiao-min Yu Li-qing Zhu Chang-quan Ling Shanghai University of Traditional Chinese Medicine Shanghai 201203China Oncology Department of Traditional Chinese Medicine Changhai HospitalNaval Medical UniversityShanghai 200433China Faculty of Traditional Chinese Medicine Naval Medical UniversityShanghai 200043China State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology(Ministry of Education) School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200438China Yantai Fuheng Biological Technology Co. Ltd.YantaiShandong Province 264006China. Department of Clinical Laboratory the First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina

Objective Melittin and its derivatives have been characterized to establish effective gene delivery *** capability of facilitating endosomal release enhances the nanoparticles-based gene ***,little investigation has been conducted to explore its potential application in the context of viral *** Various melittin-derived peptides were inserted into the loop VIII of the capsid proteins of recombinant adeno-associated virus *** vectors carrying either gfp or fluc genes were subjected to qPCR assays and transduction assays of HEK2.3T cells to investigate the efficiency of vector production and gene *** addition,the ability of a specific p5RHH-rAAV vector to deliver genes was examined through in vitro transduction of different cultured cells and in vivo tail vein administration to C57BL/6 ***,the intricate details of the vector-mediated transduction mechanisms were revealed by specific pharmacological inhibitors of every stage of the rAAV2.intracellular life *** A total of 76 melittin-related peptides were compiled from existing *** them,cMA2.Melt13,p5RHH and aAR3 were found to significantly enhance the gene delivery efficiency of rAAV2.*** p5RHH-rAAV2.vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to ***,bafilomycin A1,a vacuolar endosome acidification inhibitor,completely inhibited the transgene expression mediated by the p5RHH-rAAV2.*** importantly,p5RHH-rAAV8 vectors also demonstrated increased hepatic transduction in vivo in C57BL/6 *** The incorporation of melittin analogues into the rAAV capsids results in a significant improvement in rAAV-mediated transgene *** further modifications remain an area of interest,our studies have substantially broadened the pharmacological prospects of melittin in the context of viral vector-mediated gene delivery.

关键词： Melittin Recombinant adeno-associated virus Capsid engineering Transduction efficiency

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Mitigated reaction kinetics between lithium metal anodes and electrolytes by alloying lithium metal with low-content magnesium

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Journal of Energy Chemistry 2024年第8期95卷 644-650,I0014页

作者： Yang-Yang Wang Ya-Nan Wang Nan Yao Shu-Yu Sun Xiao-qing Ding Chen-Xi Bi Qian-Kui Zhang Zhao Zheng Cheng-Bin Jin Bo-quan Li Xue-Qiang Zhang Jia-Qi Huang School of Materials Science and Engineering Beijing Institute of TechnologyBeijing 100081China Advanced Research Institute of Multidisciplinary Science Beijing Institute of TechnologyBeijing 100081China Beijing Key Laboratory of Green Chemical Reaction Engineering and Technology Department of Chemical EngineeringTsinghua UniversityBeijing 100084China College of Materials and Chemistry China Jiliang UniversityHangzhou 310018ZhejiangChina

Lithium(Li)metal is regarded as a promising anode candidate for high-energy-density rechargeable ***,Li metal is highly reactive against electrolytes,leading to rapid decay of active Li metal ***,alloying Li metal with low-content magnesium(Mg)is proposed to mitigate the reaction kinetics between Li metal anodes and *** atoms enter the lattice of Li atoms,forming solid solution due to the low amount(5 wt%)of *** atoms mainly concentrate near the surface of Mg-alloyed Li metal *** reactivity of Mg-alloyed Li metal is mitigated kinetically,which results from the electron transfer from Li to Mg atoms due to the electronegativity *** on quantitative experimental analysis,the consumption rate of active Li and electrolytes is decreased by using Mgalloyed Li metal anodes,which increases the cycle life of Li metal batteries under demanding ***,a pouch cell(1.2. Ah)with Mg-alloyed Li metal anodes delivers an energy density of 340 Wh kg^(-1)and a cycle life of 100 *** work inspires the strategy of modifying Li metal anodes to kinetically mitigate the side reactions with electrolytes.

关键词： Lithium metal anodes Alloying Anode/electrolyte interface Reaction kinetics Pouch cell

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Triple points and phase transitions of D-dimensional dyonic Ad S black holes with quasitopological electromagnetism in Einstein–Gauss–Bonnet gravity

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Chinese Physics B 2024年第6期33卷 272-287页

作者：牟平辉蒋青权何柯腱李国平 School of Physics and Astronomy China West Normal UniversityNanchong 637000China College of Physics Chongqing UniversityChongqing 401331China

By considering the negative cosmological constant Λ as a thermodynamic pressure, we study the thermodynamics and phase transitions of the D-dimensional dyonic Ad S black holes(BHs) with quasitopological electromagnetism in Einstein–Gauss–Bonnet(EGB) gravity. The results indicate that the small/large BH phase transition that is similar to the van der Waals(vdW) liquid/gas phase transition always exists for any spacetime dimensions. Interestingly, we then find that this BH system exhibits a more complex phase structure in 6-dimensional case that is missed in other ***, it shows for D = 6 that we observed the small/intermediate/large BH phase transitions in a specific parameter region with the triple point naturally appeared. Moreover, when the magnetic charge turned off, we still observed the small/intermediate/large BH phase transitions and triple point only in 6-dimensional spacetime, which is consistent with the previous results. However, for the dyonic Ad S BHs with quasitopological electromagnetism in Einstein–Born–Infeld(EBI) gravity, the novel phase structure composed of two separate coexistence curves observed by Li et al. [Phys. Rev. D105 104048(2.2.)] disappeared in EGB gravity. This implies that this novel phase structure is closely related to gravity theories, and seems to have nothing to do with the effect of quasitopological electromagnetism. In addition, it is also true that the critical exponents calculated near the critical points possess identical values as mean field theory. Finally, we conclude that these findings shall provide some deep insights into the intriguing thermodynamic properties of the dyonic Ad S BHs with quasitopological electromagnetism in EGB gravity.

关键词： AdS black hole phase transition triple point

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