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Convergent synthesis and immunological study of oligosaccharide derivatives related to galactomannan from Antrodia cinnamomea

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Chinese Chemical Letters 2024年第5期35卷 155-160页

作者： Shuying Li Weiwei ZhuGe Xuan Sun Chongzhen Sun Zhaojun Liu Chenghe Xiong Min Xiao Guofeng Gu National Glycoengineering Research center and Shandong Key Laboratory of Carbohydrate Chemistry and glycobiology Shandong UniversityQingdao 266237China NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-based Medicine Shandong UniversityQingdao 266237China

The galactomannan from Antrodia cinnamomea(AC)is characterized as one of the important bioactive components that exhibits potential immunostimulatory *** biological function of its corresponding oligosaccharide fragments has not been revealed *** this study,we reported the first chemical synthesis of the series of oligosaccharide fragments related to AC galactomannan via the convergent glycosylation *** preliminary immunological evaluation of these synthesized AC oligosaccharides disclosed that the backbone tetrasaccharide 1d showed the best immunomodulatory ability on enhancing proliferation,phagocytosis and cytokines secretion of Raw264.7 macrophages in vitro,indicating its immense potential as an immunostimulant candidate.

关键词： Antrodia cinnamomea Galactomannan Oligosaccharide Immunostimulatory propriety Chemical synthesis

Semisynthesis of homogeneous spike RBD glycoforms from SARS-CoV-2 for profiling the correlations between glycan composition and function

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National Science Review 2024年第2期11卷 145-154页

作者： Farong Ye Cheng Li Feng-Liang Liu Xinliang Liu Peng Xu Rong-Hua Luo Wenping Song Yong-Tang Zheng Tianlei Ying Biao Yu Ping Wang center for Chemical glycobiology Frontiers Science Center for Transformative Molecules Zhangjiang Institute for Advanced Study School of Chemistry and Chemical Engineering Shanghai Jiao Tong University MOE/NHC/CAMS Key Laboratory of medical Molecular Virology Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection Shanghai Institute of Infectious Disease and BiosecurityShanghai Engineering Research Center for Synthetic ImmunologySchool of Basic Medical Sciences Shanghai Medical College Fudan University Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province Center for Biosafety Mega-Science Kunming Institute of ZoologyChinese Academy of Sciences State Key Laboratory of Bioorganic and Natural Products Chemistry Center for Excellence in Molecular Synthesis Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shenzhen Research Institute of Shanghai Jiao Tong University

Vaccines have been the primary remedy in the global fight against coronavirus disease 2019（COVID-19）.The receptor-binding domain（RBD） of the spike protein, a critical viral immunogen, is affected by the heterogeneity of its glycan structures and relatively low immunogenicity. Here, we describe a scalable synthetic platform that enables the precise synthesis of homogeneously glycosylated RBD, facilitating the elucidation of carbohydrate structure–function relationships. Five homogeneously glycosylated RBDs bearing biantennary glycans were prepared, three of which were conjugated to T-helper epitope(Tpep) from tetanus toxoid to improve their weak immune response. Relative to natural HEK293-derived RBD, synthetic RBDs with biantennary N-glycan elicited a higher level of neutralising antibodies against SARS-CoV-2 in mice. Furthermore, RBDs containing Tpepelicited significant immune responses in transgenic mice expressing human angiotensin-converting enzyme 2. Our collective data suggest that trimming the N-glycans and Tpepconjugation of RBD could potentially serve as an effective strategy for developing subunit vaccines providing efficient protection.

关键词： peptide ligation glycosylation glycoprotein

Emergency department management of acute agitation in the reproductive age female and pregnancy

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World Journal of Emergency Medicine 2024年第2期15卷 83-90页

作者： Ariella Gartenberg Kayla Levine Alexander Petrie Department of Emergency Medicine Jacobi Medical Center and Montefiore Medical CenterNY 10461USA Department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine and Montefiore Medical CenterNY 10461USA Department of Emergency Medicine Jacobi Medical Center and North Central Bronx HospitalNY 10461USA

BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and *** safety of psychotropic medications in the reproductive age female has not been well *** review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during ***:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant ***:While nonpharmacological management is preferred,ED visits for agitation often require medical *** should be selected based on the etiology of agitation and the clinical setting to avoid major adverse *** effects are common in pregnant *** mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse *** moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on *** has become the most frequently utilized psychotropic for agitation during *** generation psychotropics are often utilized as second-line therapy,including *** and ketamine have demonstrated adverse fetal ***:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in *** the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.

关键词： Agitation Pregnancy Haloperidol Ketamine Benzodiazepines

Encouraging Solution to the Problem of Synthesizing Protein α-Thioester

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Chinese Journal of Chemistry 2024年第10期42卷 1114-1120页

作者： Xinliang Liu Zijun Gao Jie Zhao Farong Ye Ping Huang Ping Wang center for Chemical glycobiology Shanghai Key Laboratory for Molecular Engineering of Chiral DrugsFrontiers Science Center for Transformative MoleculesSchool of Chemistry and Chemical EngineeringZhangjiang Institute for Advanced StudyShanghai JiaoTongUniversityShanghai 200240China Shenzhen Research Institute of Shanghai Jiao Tong University ShenzhenGuangdong 518057China

Expressed protein ligation(EPL)provides a powerful tool to access large-size proteins with precise *** methods for constructing the critical protein thioester for EPL have predominantly relied on the recombinant intein fusion expressed in Escherichia coli(***).Despite its powerful applications,the expression of thioester derived from eukaryotic protein in *** inherently suffers from its limited solubility,the inactivity of intein,premature hydrolysis and low *** overcome these obstacles,we present herein the facile one-flask synthesis of inaccessible proteinα-thioester via a SUMO-protein-intein(SPI)sandwich *** utility of SUMO enhances the protein fusion yield and solubility,prevents premature hydrolysis and simplifies the purification *** inaccessible protein thioester with internal Cys residues can be readily produced and is compatible with the EPL-desulfurization protocol used to prepare complex proteins,which is otherwise difficult to obtain using traditional *** utility has been highlighted through the synthesis of human granulocyte colony-stimulating factor(G-CSF).

关键词： Desulfurization Glycoproteins Glycopeptides Protein expression Peptide thioester

CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University medical center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

Movement Trend Alterations in the Periaqueductal Gray(PAG)-Employed Ratbot Navigation Are Correlated with Stimulation Parameters

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Journal of Bionic Engineering 2024年第2期21卷 866-876页

作者： Sina Khajei Abed Khorasani Mohammad Reza Afarinesh Vahid Sheibani Neuroscience Research center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran Cognitive Neuroscience Research center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran

In previous studies,Periaqueductal Gray(PAG)stimulation was used to stop ratbots from *** to the homology between the PAG and the intercollicular nucleus,which has been used for forward movement in birds,we investigated the possibility of PAG application to induce forward locomotion for the first *** a corridor maze,the traveled distances via PAG electrical stimulation were examined in nine Wistar male rats during three sessions.A custom-designed stimulator was developed to apply the *** results showed reductions in responses to stimulation over ***,the traveled distances had negative slopes during the consecutive trials(in 8 out of the 9 rats),and the slope mean was significantly different from *** was a strong correlation between the stimulation parameters(electric Charge per Phase(CPP)and the Number of Pulses(NP))and the observed *** negative Movement Slopes(MS)were highly correlated with the CPP and the NP,as the Pearson's linear correlation coefficients were−0.87 and−0.79,*** MS-CPP coefficients of determination(R-squared)were also between 0.76 and *** addition,the MS-NP coefficients of determination were between 0.63 and ***,it is concluded that the electrical stimulation parameters influence the behavioral outcomes ***,the PAG area may be considered a suitable candidate for forward locomotion control in the future if the area is harnessed effectively to prevent undesirable chaotic behaviors.

关键词： Periaqueductal Gray(PAG) Navigation Ratbot Animal-robot Forward locomotion Movement slope

Urgent call for attention to diabetes-associated hospital infections

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World Journal of Diabetes 2024年第8期15卷 1683-1691页

作者： Xue-Lu Yu Li-Yun Zhou Xiao Huang Xin-Yue Li Qing-Qing Pan Ming-Ke Wang Ji-Shun Yang Department of Disease Control and Prevention Naval Medical Center of PLANaval Medical UniversityShanghai 200052China medical Care center Naval Medical Center of PLANaval Medical UniversityShanghai 200052China

In this editorial,we discuss the recent article by Zhao et al published in the World Journal of Diabetes,which highlights the importance of recognizing the risk indicators associated with diabetes mellitus(DM).Given the severe implications of healthcare-associated infections(HAIs)in hospitalized individuals-such as heightened mortality rates,prolonged hospitalizations,and increased costs-we focus on elucidating the connection between DM and nosocomial *** patients are susceptible to pathogenic bacterial invasion and subsequent infection,with some already harboring co-infections upon ***,DM is an important risk factor for nosocomial urinary tract infections and surgical site infections,which may indirectly affect the occurrence of nosocomial bloodstream infections,especially in patients with DM with poor glycemic *** evidence regarding the impact of DM on healthcare-associated pneumonias remains inconclusive,attention to this potential association is *** patients with DM should prioritize meticulous blood glucose management,adherence to standard operating procedures,hand hygiene practices,environmental disinfection,and rational use of drugs during *** studies are imperative to explore the main risk factors of HAIs in patients with DM,enabling the development of preventative measures and mitigating the occurrence of HAIs in these patients.

关键词： Diabetes mellitus Healthcare-associated infections Nosocomial urinary tract infections Surgical site infections Nosocomial bloodstream infections

Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways

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Military medical Research 2024年第4期11卷 500-520页

作者： Kun Zhang Meng-Xia Zhang Xiao-Xiang Meng Jing Zhu Jia-Jun Wang Yi-Fan He Ye-Hua Li Si-Cong Zhao Zhe-Min Shi Li-Na Zheng Tao Han Wei Hong Department of Histology and Embryology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Department of Hepatology and Gastroenterology Tianjin Union Medical CenterTianjin Medical UniversityTianjin Union Medical Center Affiliated to Nankai UniversityTianjin 300000China

Background:G-protein coupled receptors(GPCRs)are recognized as attractive targets for drug ***,it remains poorly understood how GPCRs,except for a few chemokine receptors,regulate the progression of liver ***,we aimed to reveal the role of GPR65,a proton-sensing receptor,in liver fibrosis and to elucidate the underlying ***:The expression level of GPR65 was evaluated in both human and mouse fibrotic ***,Gpr65-deficient mice were treated with either bile duct ligation(BDL)for 21 d or carbon tetrachloride(CCl4)for 8 weeks to investigate the role of GPR65 in liver fibrosis.A combination of experimental approaches,including Western blotting,quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR),and enzyme-linked immunosorbent assay(ELISA),confocal microscopy and rescue studies,were used to explore the underlying mechanisms of GPR65’s action in liver ***,the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was ***:We found that hepatic macrophage(HM)-enriched GPR65 was upregulated in both human and mouse fibrotic ***,knockout of Gpr65 significantly alleviated BDL-and CCl4-induced liver inflammation,injury and fibrosis in vivo,and mouse bone marrow transplantation(BMT)experiments further demonstrated that the protective effect of Gpr65knockout is primarily mediated by bone marrow-derived macrophages(BMMs).Additionally,in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited,while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β),all of which subsequently promoted the activation of hepatic stellate cells(HSCs)and the damage of hepatocytes(HCs).Mechanistically,GPR65 overexpression,the acidic pH and GPR65 exogenous agonist induced up-regulation of

关键词： GPR65 Hepatic fibrosis Hepatic macrophages Inflammation c-Jun N-terminal kinase Nuclear factorκB

Haemorrhage after thrombectomy with adjuvant thrombolysis in unknown onset stroke depends on high early lesion water uptake

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Stroke & Vascular Neurology 2024年第4期9卷 390-398页

作者： Gabriel Broocks Lukas Meyer Uta Hanning Tobias Djamsched Faizy Matthias Bechstein Helge Kniep Noel Van Horn Gerhard Schön Ewgenia Barow Götz Thomalla Jens Fiehler Andre Kemmling Department of Diagnostic and Interventional Neuroradiology University Medical Center Hamburg-EppendorfHamburgGermany Department of medical Biometry and Epidemiology University Medical Center Hamburg EppendorfHamburgGermany Department of Neurology University Medical Center Hamburg-EppendorfHamburgGermany Department of Neuroradiology University MarburgMarburgGermany

Background and purpose In wake-up stroke,CT-based quantitative net water uptake(NWU)might serve as an alternative tool to MRI to guide intravenous thrombolysis with alteplase(IVT).An important complication after IVT is symptomatic intracerebral haemorrhage(sICH).As NWU directly implies ischaemic lesion progression,reflecting blood-brain barrier injury,we hypothesised that NWU predicts sICH in patients who had a ischaemic stroke undergoing thrombectomy with unknown *** Consecutive analysis of all patients who had unknown onset anterior circulation ischaemic stroke who underwent CT at baseline and endovascular treatment between December 2016 and October *** NWU was assessed on baseline *** primary endpoint was *** association of NWU and other baseline parameters to sICH was investigated using inverse-probability weighting(IPW)*** A total of 88 patients were included,of which 46 patients(52.3%)received *** median NWU was 10.7%(IQR:5.1–17.7).The proportion of patients with any haemorrhage and sICH were 35.2%and 13.6%.NWU at baseline was significantly higher in patients with sICH(19.1%vs 9.6%,p<0.0001)and the median Alberta Stroke Program Early CT Score(ASPECTS)was lower(5 vs 8,p<0.0001).Following IPW,there was no association between IVT and sICH in unadjusted ***,after adjusting for ASPECTS and NWU,there was a significant association between IVT administration and sICH(14.6%,95%CI:3.3%to 25.6%,p<0.01).Conclusion In patients with ischaemic stroke with unknown onset,the combination of high NWU with IVT is directly linked to higher rates of *** ASPECTS for evaluating the extent of the early infarct lesion,quantitative NWU could be used as an imaging biomarker to assess the degree of blood-brain barrier damage in order to predict the risk of sICH in patients with wake up stroke.

关键词： throm thrombolysis high