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Glucocorticoids-based prodrug design:Current strategies and research progress

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Asian Journal of Pharmaceutical Sciences 2024年第3期19卷 41-78页

作者： Hongbing Liu Muse Ji Peifu Xiao Jingxin Gou tian Yin Haibing He Xing Tang yu Zhang Department of Pharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China School of Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China

Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus,nephritis,arthritis,ulcerative colitis,asthma,keratitis,macular edema,and ***,longterm use often causes undesirable side effects,including metabolic disorders-induced Cushing's syndrome(buffalo back,full moon face,hyperglycemia,etc.),osteoporosis,aggravated infection,psychosis,glaucoma,and *** notorious side effects seriously compromise patients'quality of life,especially in patients with chronic ***,glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive *** them,prodrugs have the advantages of low investment,low risk,and high success rate,making them a promising *** this review,we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades,including polymer-based prodrugs,dendrimer-based prodrugs,antibody-drug conjugates,peptide-drug conjugates,carbohydrate-based prodrugs,aliphatic acid-based prodrugs and so ***,we also raise issues that need to be focused on during the development of glucocorticoid-based *** review is expected to be helpful for the research and development of novel GCs and prodrugs.

关键词： Glucocorticoids Prodrug design Targeted drug delivery Research progress

Peritoneal fluid indocyanine green test for diagnosis of gut leakage in anastomotic leakage rats and colorectal surgery patients

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1825-1834页

作者： yu Huang tian-Yang Li Jie-Feng Weng Hui Liu yu-Jie Xu Shuai Zhang Wei-Li Gu Department of Surgery Guangzhou First People's HospitalGuangzhou 510180Guangdong ProvinceChina

BACKGROUND Application of indocyanine green(ICG)fluorescence has led to new developments in gastrointestinal ***,little is known about the use of ICG for the diagnosis of postoperative gut leakage(GL).In addition,there is a lack of rapid and intuitive methods to definitively diagnose postoperative *** To investigate the effect of ICG in the diagnosis of anastomotic leakage in a surgical rat GL model and evaluate its diagnostic value in colorectal surgery *** Sixteen rats were divided into two groups:GL group(n=8)and sham group(n=8).Approximately 0.5 mL of ICG(2.5 mg/mL)was intravenously injected *** peritoneal fluid was collected for the fluorescence test at 24 and 48 *** patients with rectal cancer who had undergone laparoscopic rectal cancer resection plus enterostomies were injected with 10 mL of ICG(2.5 mg/mL)on postoperative day *** ostomy fluids were collected 24 h after ICG injection to identify the possibility of the ICG excreting from the peripheral veins to the enterostomy *** who had undergone colectomy or rectal cancer resection were enrolled in the diagnostic *** peritoneal fluids from drainage were collected 24 h after ICG *** ICG fluorescence test was conducted using OptoMedic endoscopy along with a near-infrared fluorescent imaging *** The peritoneal fluids from the GL group showed ICG-dependent green fluorescence in contrast to the sham *** samples of ostomy fluids showed green fluorescence,indicating the possibility of ICG excreting from the peripheral veins to the enterostomy stoma in *** peritoneal fluid ICG test exhibited a sensitivity of 100%and a specificity of 83.3%for the diagnosis of *** positive predictive value was 71.4%,while the negative predictive value was 100%.The likelihood ratios were 6.0 for a positive test result and 0 for a negative *** The postoperative ICG test in a drainage tube is a valuable and simple t

关键词： Gut leakage Indocyanine green Anastomotic leakage model Diagnostic test Diagnostic technique

Cyclic Dinucleotide Self-Assembled Nanoparticles as a Carrier-Free Delivery Platform for STING-Mediated Cancer Immunotherapy

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CCS Chemistry 2024年第1期6卷 177-195页

作者： Lang Zhao Shao-Hua zhuo tian-Yang Wang Jun-Jun Wu Jing-yun Su Wen-Hao Li Bo-Dou Zhang Yan-Mei Li Key Lab of Bioorganic Phosphorus Chemistry&Chemical Biology Department of ChemistryTsinghua UniversityBeijing 100084 Beijing Institute for Brain Disorders Beijing 100069 Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084

Cyclic dinucleotides(CDNs)are natural agonists of the stimulator of interferon genes(STING),which is an attractive immunotherapy ***,CDNs and their derivatives are being investigated ***,the poor bioavailability of exogenous CDNs has limited their application in *** nanocarriers are widely used for cytosolic delivery of CDNs,their loading capacity is insufficient,and their complicated composition and purification process raises bio-compatibility ***,we report a super-simplified CDN self-assembly strategy for carrier-free delivery of *** the presence of excess K^(+),CDNs form oligomers which further self-assemble with divalent metal ions(such as Mn^(2+))to form nanoparticles(NPs)in aqueous *** demonstrate that the self-assembled CDN NPs promote cellular uptake of CDNs and enhance tumor immunogenicity by remodeling the tumor microenvironment,inducing immunogenic tumor cell death and increasing tumorinfiltrating lymphocytes,which is conducive to the generation of tumor neoantigen-specific T-cell *** also demonstrate that the use of CDN NPs alone or in combination with immune checkpoint blockades inhibits tumor growth,highlighting the fact that CDN NPs are a potent platform for cancer immunotherapy.

关键词： cyclic dinucleotide STING carrierfree delivery tumor immunogenicity cancer immunotherapy

Electrically tunable phase-change metasurface for dynamic infrared thermal camouflage

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Photonics Research 2024年第2期12卷 292-300页

作者： yuFENG XIONG yuNZHENG WANG CHAO FENG YAOLAN tian LIANG GAO JUN-LEI WANG ZHUANG zhuo XIAN ZHAO Center for Optics Research and Engineering Key Laboratory of Laser&Infrared SystemMinistry of EducationShandong UniversityQingdao 266237China School of Information Science and Engineering Shandong UniversityQingdao 266237China

Dynamic infrared thermal camouflage technology has attracted extensive attention due to its ability to thermally conceal targets in various environmental backgrounds by tuning thermal *** use of phase change materials(PCMs)offers numerous advantages,including zero static power,rapid modulation rate,and large emissivity tuning ***,existing PCM solutions still encounter several practical application challenges,such as temperature uniformity,amorphization achievement,and adaptability to different *** this paper,we present the design of an electrically controlled metal-insulator-metal thermal emitter based on a PCM metasurface,and numerically investigate its emissivity tunability,physical mechanisms,heat conduction,and thermal camouflage performance across different ***,the influence of the quench rate on amorphization was studied to provide a guidance for evaluating and optimizing device *** results reveal that the thermal emitter exhibits a wide spectral emissivity tuning range between 8 and 14μm,considerable quench rates for achieving amorphization,and the ability to provide thermal camouflage across a wide background temperature ***,it is anticipated that this contribution will promote the development of PCM-based thermal emitters for practical dynamic infrared thermal camouflage technology with broad applications in both civilian and military domains.

关键词： thermal dynamic phase

Bovine and Goat Milk Fat Globule Membrane Supplementation Alleviates Autism-like Behavior by Modulating Lipid Metabolism and Gut Microbiota

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Food Science and Human Wellness 2024年

作者： Rui Guo Xiao Xiao Chuanchuan Wang tian yuan Qianhui Zou tian Zhang Jiarui Liang Ying He zhuo Liu Xuebo Liu Shan Wu Zhigang Liu Northwest A&F University Shenzhen Research Institute Shaanxi Precision Nutrition and Health Research Institute Research and Development Center， Xi'an Yinqiao Dairy (Group) Co.， Ltd Laboratory of Functional Chemistry and Nutrition of Food， College of Food Science and Engineering， Northwest A&F University Shaanxi Key Laboratory of Natural Products & Chemical Biology， College of Chemistry & Pharmacy， Northwest A&F University

ASD (autism spectrum disorder) is a neurodevelopmental disorder influenced by genes and the environment. This study investigated the protective effects of bovine MFGM (BMFGM) and goat MFGM (GMFGM) supplementation on ASD model mice. Analysis of phospholipid composition showed higher levels of phosphatidylcholine in BMFGM and phosphatidylethanolamine in GMFGM. Behavioral results indicated MFGMs ameliorated social deficits， with GMFGM being more effective. MFGMs mitigated neuroinflammation by suppressing microglial overactivation and proinflammatory cytokines expression， meanwhile GMFGM increased the anti-inflammatory factor IL-10. MFGMs also altered gut microbiota composition and maintained gut barrier integrity. Uniquely， GMFGM increased butyrate production. Correlation analysis revealed positive associations between social behavior， levels of phosphatidylcholine， sphingomyelin， and the abundance of Allobaculum， Clostridium＿sensu＿stricto， and Turicibacter. Overall， these findings revealed the protective effects of MFGMs on neurodevelopment in ASD animal models and the underlying mechanism could be partly explained by their regulation of gut microbiota by the phospholipid components in MFGMs.

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Wear-resistant Ag-MAX phase 3D interpenetrating-phase composites:Processing,structure,and properties

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Nano Research 2024年第2期17卷 806-819页

作者： yu Guo Xi Xie Zengqian Liu Longchao zhuo Jian Zhang Shaogang Wang Qiqiang Duan Qing Jia Dake Xu Weihai Xue Deli Duan Filippo Berto Zhefeng Zhang Rui Yang Shi-Changxu Innovation Center for Advanced Materials Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Materials Science and Engineering University of Science and Technology of ChinaHefei 230026China School of Materials Science and Engineering Xi’an University of TechnologyXi’an 710048China Electrobiomaterials Institute Key Laboratory for Anisotropy and Texture of Materials(Ministry of Education)Northeastern UniversityShenyang 110819China Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China Department of Chemical Engineering Materials and EnvironmentSapienza University of RomeRoma 00185Italy

Electrical contact materials are generally Ag-or Cu-based composites and play a critical role in ensuring the reliability and efficiency of electrical equipments and electronic *** MAX(M is an early transition metal,A is an element from III or IV main groups,and X is carbon or/and nitrogen)phase ceramics display a unique combination of properties and may serve as an ideal reinforcement phase for electrical contact *** biological materials evolved in nature generally exhibit three-dimensional(3D)interpenetrating-phase architectures,which may offer useful inspiration for the architectural design of electrical contact ***,a series of bi-continuous Ag-Ti_(3)SiC_(2) MAX phase composites with high ceramic contents exceeding 50 vol.%and having micron-and ultrafine-scaled 3D interpenetrating-phase architectures,wherein both constituents were continuous and mutually interspersed,were exploited by pressureless infiltration of Ag melt into partially sintered Ti_(3)SiC_(2) *** mechanical and electrical properties as well as the friction and wear performance of the composites were investigated and revealed to be closely dependent on the ceramic contents and characteristic structural *** composites exhibited a good combination of properties with high hardness over 2.3 GPa,high flexural strength exceeding 530 MPa,decent fracture toughness over 10 MPa·m^(1/2),and good wear resistance with low wear rate at an order of 10^(-5)mm^(3)/(N·m),which were much superior compared to the counterparts made by powder metallurgy *** particular,the hardness,electrical conductivity,strength,and fracture toughness of the composites demonstrated a simultaneous improvement as the structure was refined from micron-to ultrafine-scales at equivalent ceramic *** good combination of properties along with the facile processing route makes the Ag-Ti_(3)SiC_(2)3D interpenetrating-phase composites appealing for electrical contact applicatio

关键词： three-dimensional(3D)interpenetrating-phase architecture Ag-MAX(M=early transition metal A=element from III or IV main groups and X=carbon or/and nitrogen)phase composites melt infiltration electrical contact materials mechanical

Protein C deficiency with venous and arterial thromboembolic events

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World Journal of Clinical Cases 2024年第12期12卷 2000-2003页

作者： Nan Zhang Dong-Kun Sun Xu tian Xin-yu Zheng Tong Liu Department of Cardiology Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular DiseaseTianjin Institute of CardiologyThe Second Hospital of Tianjin Medical UniversityTianjin 300211China

Protein C(PC)is a key component of the vitamin K-dependent coagulation *** exerts anticoagulant effects by inactivating factors V and *** or inherited PC deficiency results in a prothrombotic state,with presentations varying from asymptomatic to venous ***,there has been an increasing number of reports linking PC deficiency to arterial thromboembolic events,such as myocardial infarction and ischemic *** editorial focuses on the association between PC deficiency and thromboembolism,which may provide some insights for treatment strategy and scientific research.

关键词： Protein C deficiency Venous thromboembolism Myocardial infarction Editorial Arterial thromboembolism

Zonal activation of molecular carbon dioxide and hydrogen over dual sites Ni-Co-MgO catalyst for CO_(2) methanation:Synergistic catalysis of Ni and Co species

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Journal of Energy Chemistry 2024年第4期91卷 213-225页

作者： Zonglin Li Jianjun Chen yu Xie Junjie Wen Huiling Weng Mingxue Wang Jingyi Zhang Jinyan Cao Guocai tian Qiulin Zhang Ping Ning Faculty of Environmental Science and Engineering Kunming University of Science and TechnologyKunming 650500YunnanChina National-Regional Engineering Center for Recovery of Waste Gases from Metallurgical and Chemical Industries Kunming University of Science and TechnologyKunming 650500YunnanChina Faculty of Metallurgical and Energy Engineering Kunming University of Science and TechnologyKunming 650093YunnanChina

An in-depth mechanism in zonal activation of CO_(2)and H2molecular over dual-active sites has not been revealed ***,Ni-Co-MgO was rationally constructed to elucidate the CO_(2)methanation *** abundant surface nickel and cobalt components as active sites led to strong Ni-Co interaction with charge transfer from nickel to ***,electron-enriched Coδ-species participated in efficient chemisorption and activation of CO_(2)to generate monodentate ***,plentiful available Ni0sites facilitated H2dissociation,thus CO_(2)and H2were smoothly activated at zones of Coδ-species and Ni0,*** in situ DRIFTS,quasi situ XPS,TPSR,and DFT calculations substantiated a new formate evolution mechanism via monodentate carbonate instead of traditional bidentate carbonate based on synergistic catalysis of Coδ-species and *** zonal activation of CO_(2)and H2by tuning electron behaviors of double-center catalysts can boost heterogeneous catalytic hydrogenation performance.

关键词： Zonal activation CO_(2) methanation Dual active sites Synergistic effect

What benefit can be obtained from magnetic resonance imaging diagnosis with artificial intelligence in prostate cancer compared with clinical assessments?

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Military Medical Research 2024年第2期11卷 268-286页

作者： Li-Tao Zhao Zhen-yu Liu Wan-Fang Xie Li-Zhi Shao Jian Lu Jie tian Jian-Gang Liu School of Engineering Medicine Beihang UniversityBeijing 100191China School of Biological Science and Medical Engineering Beihang UniversityBeijing 100191China CAS Key Laboratory of Molecular Imaging Institute of AutomationBeijing 100190China University of Chinese Academy of Sciences Beijing 100080China Department of Urology Peking University Third HospitalPeking UniversityBeijing 100191China Key Laboratory of Big Data‑Based Precision Medicine(Beihang University) Ministry of Industry and Information Technology of the People's Republic of ChinaBeijing 100191China Beijing Engineering Research Center of Cardiovascular Wisdom Diagnosis and Treatment Beijing 100029China

The present study aimed to explore the potential of artificial intelligence(AI)methodology based on magnetic resonance(MR)images to aid in the management of prostate cancer(PCa).To this end,we reviewed and summarized the studies comparing the diagnostic and predictive performance for PCa between AI and common clinical assessment methods based on MR images and/or clinical characteristics,thereby investigating whether AI methods are generally superior to common clinical assessment methods for the diagnosis and prediction fields of ***,we found that,in the included studies of the present study,AI methods were generally equal to or better than the clinical assessment methods for the risk assessment of PCa,such as risk stratification of prostate lesions and the prediction of therapeutic outcomes or PCa *** particular,for the diagnosis of clinically significant PCa,the AI methods achieved a higher summary receiver operator characteristic curve(SROC-AUC)than that of the clinical assessment methods(0.87 vs.0.82).For the prediction of adverse pathology,the AI methods also achieved a higher SROC-AUC than that of the clinical assessment methods(0.86 vs.0.75).Second,as revealed by the radiomics quality score(RQS),the studies included in the present study presented a relatively high total average RQS of 15.2(11.0–20.0).Further,the scores of the individual RQS elements implied that the AI models in these studies were constructed with relatively perfect and standard radiomics processes,but the exact generalizability and clinical practicality of the AI models should be further validated using higher levels of evidence,such as prospective studies and open-testing datasets.

关键词： Clinically significant prostate cancer Adverse pathology Radiomics quality score Artificial intelligence Magnetic resonance imaging