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Semaglutide for the management of diabesity:The real-world experience

World Journal of Methodology 2024年第3期14卷 68-77页

作者： Mohammed Alkhalifah Hafsa Afsar Anindya Shams Dania Blaibel Vishnu Chandrabalan Joseph M Pappachan department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom department of Family Medicine King Faisal Specialist HospitalRiyadh 11211Saudi Arabia department of Data science Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom

BACKGROUND Diabesity(diabetes as a consequence of obesity)has emerged as a huge healthcare challenge across the globe due to the obesity pandemic.Judicious use of antidiabetic medications including semaglutide is important for optimal management of diabesity as proven by multiple randomized controlled trials.However,more real-world data is needed to further improve the clinical practice.AIM To study the real-world benefits and side effects of using semaglutide to manage patients with diabesity.METHODS We evaluated the efficacy and safety of semaglutide use in managing patients with diabesity in a large academic hospital in the United States.Several parameters were analyzed including demographic information,the data on improvement of glycated hemoglobin(HbA1c),body weight reduction and insulin dose adjustments at 6 and 12 months,as well as at the latest follow up period.The data was obtained from the electronic patient records between January 2019 to May 2023.RESULTS 106 patients(56 males)with type 2 diabetes mellitus(T2DM),mean age 60.8±11.2 years,mean durations of T2DM 12.4±7.2 years and mean semaglutide treatment for 2.6±1.1 years were included.Semaglutide treatment was associated with significant improvement in diabesity outcomes such as mean weight reductions from baseline 110.4±24.6 kg to 99.9±24.9 kg at 12 months and 96.8±22.9 kg at latest follow up and HbA1c improvement from baseline of 82±21 mmol/mol to 67±20 at 12 months and 71±23 mmol/mol at the latest follow up.An insulin dose reduction from mean baseline of 95±74 units to 76.5±56.2 units was also observed at the latest follow up.Side effects were mild and mainly gastrointestinal like bloating and nausea improving with prolonged use of semaglutide.CONCLUSION Semaglutide treatment is associated with significant improvement in diabesity outcomes such as reduction in body weight,HbA1c and insulin doses without major adverse effects.Reviews of largescale real-world data are expected to inform better clinical practice decision making to improve the care of

关键词： Type 2 diabetes mellitus Diabesity Glucagon-like peptide 1 receptor agonists Semaglutide Insulin dose reduction Weight loss

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Amphiphilic amino-acid derivatives promote gram-scale single-crystal COFs synthesis

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science China Chemistry 2024年第2期67卷 415-416页

作者： Yijia Yuan Kian Ping Loh department of Chemistry National University of SingaporeSingapore117543Singapore

Covalent organic frameworks(COFs) are crystalline organic compounds synthesized from covalently linked building blocks that extend in space to form a framework structure with periodic pores. The covalent linkages used... 详细信息

关键词： synthesis correction reversible

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Laser-assisted direct roller imprinting of large-area microstructured optical surfaces

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Microsystems & Nanoengineering 2024年第1期10卷 257-266页

作者： Keisuke Nagato Ken Takahashi Yuki Yajima Masayuki Nakao department of Mechanical Engineering Graduate School of EngineeringThe University of Tokyo7-3-1 HongoBunkyo-kuTokyo 113-8656Japan

In this study,a high-throughput fabrication method called laser-assisted direct roller imprinting(LADRI)was developed to lower the cost of nanoimprinting large-area polymer films and to address problems associated with nanoimprinting,namely,microstructural damage and precision in flatness of entire film.With LADRI,the laser directly heats the microstructured surface of the roller mold,which heats and melts the surface of a polymethyl methacrylate(PMMA)film to replicate the microstructures on the mold rapidly.In this study,the effects of laser power density,scanning speed,size of the microstructures,and contact pressure on the replication speed were investigated experimentally.The replication speed increased as the power and scanning speed increased.However,because the film required heating until it filled the entire depth of the microstructure,an appropriate replication speed was necessary.This result was supported by simulation of the temperature distribution inside the mold and the PMMA using transient heat conduction analyses.To demonstrate the applications of LADRI,two different optical surfaces were replicated:an antireflection(AR)structure with conical structures sized several hundred nanometers and a lightextraction structure with a microlens array(MLA)comprising 10μm lenses,for display and illumination,respectively.The replication degree of the MLA was governed by the contact pressure.Polymer flow simulation indicated that the heat conduction and flow speeds of the melted PMMA surface were comparable within several tens of micrometers.In addition,the reflectivity of the AR structure decreased from 4 to 0.5%,and the light intensity of the light-extraction structure increased by a factor of 1.47.

关键词： microstructure roller conduction

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miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1- containing AMPA receptors in a mouse model of Alzheimer’s disease

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Acta Pharmaceutica Sinica B 2024年第2期14卷 635-652页

作者： Man Luo Yayan Pang Junjie Li Lilin Yi Bin Wu Qiuyun Tian Yan He Maoju Wang Lei Xia Guiqiong He Weihong Song Yehong Du Zhifang Dong Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China department of Anatomy Basic Medical CollegeChongqing Medical UniversityChongqing 400016China Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouver BC V6T 1Z3Canada Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceZhejiang Clinical Research Center for Mental DisordersSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhou 325000China Institute for Brain science and Disease of Chongqing Medical University Chongqing 400016China

Alzheimer ’s disease(AD) is a leading cause of dementia in the elderly.Mitogen-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in AD.However,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied.MicroRNAs(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA translation.Here,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model cells.We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation.More importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

关键词： Alzheimer's disease MKP-1 miR-429-3p AMPAreceptor Learning and memory Long-term potentiation

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Landscape of global urban environmental resistome and its association with local socioeconomic and medical status

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science China(life sciences) 2024年第6期67卷 1292-1301页

作者： Jun Wu Yige Hu Michael H Perlin David Danko Jun Lu Manuela Oliveira Johannes Werner Maria M Zambrano Maria A Sierra Olayinka O Osuolale PawełŁabaj Nicolás Rascovan Nur Hazlin Hazrin-Chong Soojin Jang Haruo Suzuki Marina Nieto-Caballero Bharath Prithiviraj Patrick K H Lee Agnieszka Chmielarczyk Anna Różańska Yongxiang Zhao Lan Wang Christopher E Mason Tieliu Shi Center for Bioinformatics and Computational Biology and the Institute of Biomedical SciencesSchool of Life SciencesEast China Normal UniversityShanghai 200241China department of Biology Program on Disease EvolutionUniversity of LouisvilleLouisville 40292USA Weill Cornell Medicine New York 10065USA The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine New York 10065USA department of Pulmonary Medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200025China i3S-Instituto de Investiga玢o e Inova玢o em Saúde Universidade do PortoPorto 4050-290Portugal Ipatimup-Instituto de Patologia e Imunologia Molecular da Universidade do Porto Porto 4200-465Portugal Departamento de Biologia Faculdade de CiênciasUniversidade do PortoPorto 4050-290Portugal High Performance and Cloud Computing Group Zentrum für Datenverarbeitung(ZDV)Eberhard Karls University of TübingenW鋍hterstra遝7672074TübingenGermany Corporación Corpogen Research Center Bogotá110311Colombia Applied Environmental Metagenomics and Infectious Diseases Research(AEMIDR) Department of Biological SciencesElizade UniversityIlara-Mokin 340271Nigeria Maopolska Centre of Biotechnology Jagiellonian UniversityKraków 30-005Poland Aix-Marseille Université Mediterranean Institute of OceanologyUniversitéde ToulonCNRSIRDUM 110Marseille 83041France department of Biological sciences and Biotechnology Faculty of Science and TechnologyUniversiti Kebangsaan Malaysia43600 UKM BangiSelangor Institut Pasteur Korea Seoul 13488Republic of Korea Faculty of Environment and Information Studies Keio UniversityFujisawaKanagawa 252-0882Japan University of Colorado at Boulder CivilEnvironmental and Architectural DepartmentBoulder 80303USA Brooklyn College of the City University of New York Brooklyn 11210USA School of Energy and Environment City University of Hong KongHong Kong 999077China department of Microbiology Faculty of MedicineJagiellonian UniversityKraków 30-005Poland Biological Targeting Diagnosis and The

Antimicrobial resistance(AMR)poses a critical threat to global health and development,with environmental factors—particularly in urban areas—contributing significantly to the spread of antibiotic resistance genes(ARGs).However,most research to date has been conducted at a local level,leaving significant gaps in our understanding of the global status of antibiotic resistance in urban environments.To address this issue,we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples,which were collected by the Meta SUB International Consortium involving diverse urban environments in 60 cities of 27 countries,utilizing a deep-learning based methodology.Our findings demonstrated the strong geographical specificity of urban environmental resistome,and their correlation with various local socioeconomic and medical conditions.We also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters(BGCs)across different countries,and discovered that the urban environment represents a rich source of novel antibiotics.Our study provides a comprehensive overview of the global urban environmental resistome,and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis.

关键词： urban environment metagenome antibiotic resistance resistance diversity biosynthetic gene clusters

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Successful rescue of disseminated Nocardia infection with multiple abscesses in a patient with membranous nephropathy after cardiopulmonary resuscitation:A three-year follow-up

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Journal of Biomedical Research 2024年第2期38卷 189-194,I0019,I0020页

作者： Yili Xu Hanyang Qian Wen Qian Li Dong Weiying Liu Yan Zhu Yaning Mei Yi Xu Ling Wang Yi Xia Xu Qi Huanping Mei Xueqiang Xu Huijuan Mao Changying Xing Ningning Wang department of Nephrology the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China department of Nephrology Nanjing Tongren HospitalNanjingJiangsu 211102China department of Image the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China department of Infectious Disease the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China department of Nephrology the Second Hospital of NanjingNanjingJiangsu 210029China department of Microorganism the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China department of Hematology the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China department of Rheumatology and Immunology the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China

Nocardiosis manifests as an opportunistic infection,primarily affecting individuals who are immunocompromised and susceptible to the infection.We present a case study of one patient with nephrotic syndrome and membranous nephropathy,who underwent treatment with prednisone and cyclosporine in 2016.In early 2017,the patient was diagnosed with a"fungal infection"and discontinued the use of cyclosporine.After one month of anti-infection therapy,a cranial magnetic resonance imaging scan showed multiple abscesses in the right temporal region.The diagnosis of nocardiosis was confirmed based on the presence of metastatic abscess masses,multiple lung and brain lesions,and a positive culture of Nocardia in the drainage.We changed the anti-infection therapy to a combination of trimethoprim-sulfamethoxazole(TMP-SMX),minocycline,and voriconazole.However,the patient experienced a sudden cardiac arrest and subsequently recovered after cardiopulmonary resuscitation.During the five-month follow-up period following the discharge,the patient displayed an enhanced nutritional status and stable renal function.The focal infection ultimately resolved during the subsequent three years.Neuro-infection caused by Nocardia should be considered in immunocompromised patients,and TMP-SMX is the preferred initial therapy;however,because of the high mortality rate,a long-term combination therapy with imipenem,cefotaxime,amikacin,and TMP-SMX is suggested.

关键词： Nocardia infection glomerulonephritis membranous nephrology cardiopulmonary resuscitation

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NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 153-164页

作者： Bo Shi Cheng-Jie Lyu Zhen-Kai Le Hao-Sen Ji Yi Xiao Yuan-Yuan Zhang Shou-Jiang Huang Lin-Jun Yu Qiang Shu Jin-Fa Tou Deng-Ming Lai department of Neonatal Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China department of Pulmonology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China department of Thoracic and Cardiovascular Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China

Background Macrophages are involved in various immune inflammatory disease conditions.This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis(NEC).Methods CD68,nucleotide-binding oligomerization domain,leucine-rich repeat,and pyrin domain-containing 3(NLRP3),cysteine aspartate-specific protease-1(caspase-1),and interleukin-1β(IL-1β)in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry,immunofluorescence,and western blot.Hypertonic pet milk,hypoxia and cold stimulation were used to establish a mouse(wild type and Nlrp3^(-/-))model of NEC.The mouse macrophage(RAW 264.7)and rat intestinal epithelial cell-6 lines were also cultured followed by various treatments.Macrophages,intestinal epithelial cell injuries,and IL-1β release were determined.Results Compared to the gut“healthy”patients,the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3,caspase-1,and IL-1β levels.Furthermore,in vivo,the survival rate of Nlrp3^(-/-)NEC mice was dramatically improved,the proportion of intestinal macrophages was reduced,and intestinal injury was decreased compared to those of wild-type NEC mice.NLRP3,caspase-1,and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell injuries.Conclusions Macrophage activation may be essential for NEC development.NLRP3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development,and all these may be therapeutic targets for developing treatments for NEC.

关键词： Caspase-1 Interleukin-1β Macrophage Necrotizing enterocolitis NLRP3

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深低温保存下高效抗冻多肽的合理设计和机理探讨

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Engineering 2024年第3期34卷 164-173页

作者： Haishan Qi Yihang Gao Lin Zhang Zhongxin Cui Xiaojie Sui Jianfan Ma Jing Yang Zhiquan Shu Lei Zhang department of Biochemical Engineering School of Chemical Engineering and TechnologyFrontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(MOE)Tianjin UniversityTianjin 300350China School of Engineering and Technology University of Washington TacomaTacomaWA 98402USA

The development of effective antifreeze peptides to control ice growth has attracted a significant amount of attention yet still remains a great challenge.Here,we propose a novel design method based on in-depth investigation of repetitive motifs in various ice-binding proteins(IBPs)with evolution analysis.In this way,several peptides with notable antifreeze activity were developed.In particular,a designed antifreeze peptide named AVD exhibits ideal ice recrystallization inhibition(IRI),solubility,and biocompatibility,making it suitable for use as a cryoprotective agent(CPA).A mutation analysis and molecular dynamics(MD)simulations indicated that the Thr6 and Asn8 residues of the AVD peptide are fundamental to its ice-binding capacity,while the Ser18 residue can synergistically enhance their interaction with ice,revealing the antifreeze mechanism of AVD.Furthermore,to evaluate the cryoprotection potential of AVD,the peptide was successfully employed for the cryopreservation of various cells,which demonstrated significant post-freezing cell recovery.This work opens up a new avenue for designing antifreeze materials and provides peptide-based functional modules for synthetic biology.

关键词： Antifreeze peptides Evolution analysis Ice recrystallization inhibition Molecular dynamics simulation Cryopreservation Synthetic biology

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Rationale and design of Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events III (TRACE III): a randomised, phase III, open- label, controlled trial

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Stroke & Vascular Neurology 2024年第1期9卷 82-89页

作者： Yunyun Xiong Bruce C V Campbell Marc Fisher Lee H Schwamm Mark Parsons Hao Li Yuesong Pan Xia Meng Xingquan Zhao Yongjun Wang Neurology Beijing Tiantan HospitalBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina department of Medicine and Neurology The University of MelbourneMelbourneVictoriaAustralia Neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA department of Neurology and Comprehensive Stroke Center Massachusetts General HospitalBostonMassachusettsUSA department of Neurology University of New South Wales South Western Sydney Clinical SchoolLiverpoolNew South WalesAustralia

Background and purpose Recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)was not inferior to alteplase for ischaemic stroke within 4.5hours.Our study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion(LVO)of anterior circulation beyond 4.5hours.Methods and design Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III(TRACE III)is a multicentre,prospective,randomised,open-label,blind endpoint,controlled clinical trial.Patients who had an ischaemic stroke due to anterior circulation LVO(internal carotid artery,middle cerebral artery M1 and M2 segments)within 4.5–24hours from last known well(including wake-up stroke and no witness stroke)and with salvageable tissue(ischaemic core volume6s at 24 hours and NIHSS score change from baseline at 7days.Safety outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 days.Discussion TRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond 4.5hours.Trial registration number NCT05141305.

关键词： Therapy random Rational

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Rapid GFAP and Iba1 expression changes in the female rat brain following spinal cord injury

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Neural Regeneration Research 2022年第2期17卷 378-385页

作者： Mawj Mandwie Jordan A.Piper Catherine A.Gorrie Kevin A.Keay Giuseppe Musumeci Ghaith Al-Badri Alessandro Castorina Laboratory of Cellular and Molecular Neuroscience(LCMN) School of Life ScienceFaculty of ScienceUniversity of Technology SydneySydneyNSWAustralia Neural Injury Research Unit School of Life ScienceFaculty of ScienceUniversity of Technology SydneySydneyNSWAustralia School of Medical sciences(Neuroscience) The University of SydneySydneyNSWAustralia department of Biomedical and Biotechnological sciences AnatomyHistology and Movement Sciences SectionSchool of MedicineUniversity of CataniaCataniaItaly

Evidence suggests that rapid changes to supporting glia may predispose individuals with spinal cord injury(SCI) to such comorbidities. Here, we interrogated the expression of astrocyte-and microglial-specific markers glial fibrillary acidic protein(GFAP) and ionized calcium binding adaptor molecule 1(Iba1) in the rat brain in the first 24 hours following SCI. Female Sprague-Dawley rats underwent thoracic laminectomy;half of the rats received a mild contusion injury at the level of the T10 vertebral body(SCI group), the other half did not(Sham group). Twenty-four hours post-surgery the amygdala, periaqueductal grey, prefrontal cortex, hypothalamus, lateral thalamus, hippocampus(dorsal and ventral) in rats were collected. GFAP and Iba1 m RNA and protein levels were measured by real-time quantitative polymerase chain reaction and Western blot. In SCI rats, GFAP m RNA and protein expression increased in the amygdala and hypothalamus. In contrast, gene and protein expression decreased in the thalamus and dorsal hippocampus. Interestingly, Iba1 transcripts and proteins were significantly diminished only in the dorsal and ventral hippocampus, where gene expression diminished. These findings demonstrate that as early as 24 hours post-SCI there are region-specific disruptions of GFAP and Iba1 transcript and protein levels in higher brain regions. All procedures were approved by the University of Technology Sydney Institutional Animal Care and Ethics Committee(UTS ACEC13-0069).

关键词： affective disorders astrocytes glial fibrillary acidic protein ionized calcium binding adaptor molecule 1 memory microglia neurotrauma spinal cord injury

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