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Identification of residues in Lassa virus glycoprotein 1 involved in receptor switch

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Virologica sinica 2024年第4期39卷 600-608页

作者： Guo j. Wan Y. Liu Y. jia X. Dong s. Xiao G. Wang W. state Key Laboratory of Virology Wuhan Institute of Virology Center for Biosafety Mega-Science Chinese Academy of Sciences Wuhan 430071 China The Xi'an Key Laboratory of Pathogenic Microorganism and Tumor Immunity School of Basic Medicine Xi'an Medical University Xi'an 710021 China University of the Chinese Academy of sciences Beijing 100049 China

Lassa virus (LAsV) is an enveloped, negative-sense RNA virus that causes Lassa hemorrhagic fever. successful entry of LAsV requires the viral glycoprotein 1 (GP1) to undergo a receptor switch from its primary receptor alpha-dystroglycan (α-DG) to its endosomal receptor lysosome-associated membrane protein 1 (LAMP1). A conserved histidine triad in LAsV GP1 has been reported to be responsible for receptor switch. To test the hypothesis that other non-conserved residues also contribute to receptor switch, we constructed a series of mutant LAsV GP1 proteins and tested them for binding to LAMP1. Four residues, L84, K88, L107, and H170, were identified as critical for receptor switch. substituting any of the four residues with the corresponding lymphocytic choriomeningitis virus (LCMV) residue (L84 N, K88E, L10F, and H170s) reduced the binding affinity of LAsV GP1 for LAMP1. Moreover, all mutations caused decreases in glycoprotein precursor (GPC)-mediated membrane fusion at both pH 4.5 and 5.2. The infectivity of pseudotyped viruses bearing either GPCL84N or GPCK88E decreased sharply in multiple cell types, while L107F and H170s had only mild effects on infectivity. Using biolayer light interferometry assay, we found that all four mutants had decreased binding affinity to LAMP1, in the order of binding affinity being L84 N > L107F > K88E > H170s. The four amino acid loci identified for the first time in this study have important reference significance for the in-depth investigation of the mechanism of receptor switching and immune escape of LAsV occurrence and the development of reserve anti-LAsV infection drugs. © 2024 The Authors

关键词： Glycoprotein Lassa virus (LAsV) Lysosome-associated membrane protein 1 (LAMP1) Membrane fusion Receptor switch

Celastrol activates caspase-3/GsDME-dependent pyroptosis in tumor cells by inducing endoplasmic reticulum stress

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journal of Traditional Chinese Medical sciences 2024年第3期11卷 330-339页

作者： Guo j. Cui D. Tang Y. Wang s. Ma C. Ma W. school of Life sciences Beijing University of Chinese Medicine Beijing 102488 China These authors have contributed equally to this work. Key Laboratory of shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility Shaanxi University of Chinese Medicine Xi'an 712046 China school of Literature and History Mianyang Teachers' College Mianyang 621000 China

Objective: To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved, specifically focusing on the role of the caspase-3/gasdermin E (GsDME) signaling pathway and the impact of endoplasmic reticulum (ER) stress and autophagy. Methods: Necrostatin-1 (Nec-1), lactate dehydrogenase release (LDH) assay, and Hoechst/propidium iodide (PI) double staining were employed to validate the mode of cell death. Western blot was used to detect the cleavage of GsDME and the expression of light chain 3 (LC3) and BIP. Results: Celastrol induced cell swelling with large bubbles, which is consistent with the pyroptotic phenotype. Moreover, treatment with celastrol induced GsDME cleavage, indicating the activation of GsDME-mediated pyroptosis. GsDME knockout via CRIsPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells. In addition, cleavage of GsDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells, suggesting that GsDME activation was induced by caspase-3. Mechanistically, celastrol induced endoplasmic reticulum (ER) stress and autophagy in HeLa cells, and other ER stress inducers produced effects consistent with those of celastrol. Conclusion: These findings suggest that celastrol triggers caspase-3/GsDME-dependent pyroptosis via activation of ER stress, which may shed light on the potential antitumor clinical applications of celastrol. © 2024 Beijing University of Chinese Medicine

关键词： Caspase-3 Celastrol Cell death Endoplasmic reticulum stress stress GsDME Pyroptosis Traditional Chinese medicine Tumor cells

Mechanism of acupoint penetration acupuncture therapy regulating chondrocyte autophagy via the PI3K/Akt-mTOR pathway in KOA rats

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journal of Traditional Chinese Medical sciences 2024年第3期11卷 363-375页

作者： Gao Y. Wang Q. Li s. shi X. Dai s. Yu j. Zhao Q. Wang Y. Zhou Y. Department of Acupuncture and Moxibustion section The First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou 450000 China The two authors contributed equally to this study. Henan Province Hospital of Traditional Chinese Medicine Zhengzhou 450053 China Academy of Medical sciences Zhengzhou University Zhengzhou 450052 China Department of Anesthesiology The First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou 450000 China The First Clinical Medical College Henan University of Chinese Medicine Zhengzhou 450018 China school of International Education Henan University of Chinese Medicine Zhengzhou 450018 China

Objective: To investigate whether acupoint penetration acupuncture (APA) could regulate chondrocyte autophagy and apoptosis via the PI3K/Akt-mTOR signaling pathway to reduce cartilage degeneration in knee osteoarthritis (KOA) rats. Methods: KOA was induced in rats via intra-articular injection of sodium iodoacetate resolution. Forty male sprague-Dawley rats were randomly assigned to blank control, model, APA, electro-acupuncture (EA), and sham model groups (n = 8) and those in the APA and EA groups received their respective therapies. Following completion of the treatment course, histological examinations of cartilage and muscle were conducted. Levels of apoptosis- and autophagy-related factors, including Bax, Bcl-2, mTOR, ULK-1, and Beclin-1 protein, and mRNAs were assessed. Additionally, β-endorphin (β-EP) concentrations in the brain and serum were measured. Results: Histological analysis revealed that APA alleviated cartilage and muscle damage compared with the model group. APA inhibited cartilage degeneration by modulating the expression of apoptosis- and autophagy-related proteins and mRNA, thus preventing chondrocyte apoptosis. In the APA group, Bax and mTOR protein levels were significantly lower than those in the model group (both P = .024). Conversely, the Bcl-2 expression level was significantly higher than that in the EA group (P = .035). Additionally, ULK-1 expression was significantly lower than that in the EA group (P = .045). The mRNA level of Bax was significantly higher than that in the blank control group (P s were significantly higher than those in both the model and EA groups (both P sA results showed a significant decrease in the concentration of β-EP in the brains of the rats in the APA group compared with those in the model group (P = .032). Conclusions: APA reduced osteoarthritis-related pain and alleviated cartilage damage by upregulating chondrocyte autophagy and down-regulating apoptosis via sign

关键词： Acupoint penetration acupuncture Apoptosis Autophagy Cell proliferation Chondrocyte Knee osteoarthritis

Effect of drug therapies on self-reported chemosensory outcomes after COVID-19

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World journal of Otorhinolaryngology-Head and Neck surgery 2024年第2期10卷 88-96页

作者： Marco A.Fornazieri Bruno M.Cunha samuel P.Nicácio Lucas K.Anzolin joséL.B.da silva Aristides fernandes Neto Deusdedit Brandão Neto Richard L.Voegels Fábio D.R.Pinna Department of surgery Londrina State UniversityLondrinaBrazil Department of Medicine Pontifical Catholic University of ParanáLondrinaBrazil Department of Otorhinolaryngology University of São PauloSao PauloBrazil Department of Otorhinolaryngology:Head and Neck surgery Perelman School of MedicineSmell and Taste CenterUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA

Objective:The aim of this study was to assess the relative efficacy of medications used following severe acute respiratory syndrome coronavirus-2(sARs-CoV-2)infection on self-reported alterations in taste and/or smell ***:seven hundred and fourteen persons with self-reported postcoronavirus disease 2019(post-COVID-19)chemosensory disorders were personally interviewed regarding specific medications they were administered following the acute phase of the *** dependent measure—self-reported total recovery of chemosensory symptoms—was subjected to stepwise logistic *** predictors included demographic and clinical variables,in addition to specific medications used to mitigate disease symptoms(i.e.,systemic corticosteroids,oseltamivir,vitamin C,ibuprofen,hydroxychloroquine,azithromycin,ivermectin,nitazoxanide,anticoagulants,and zinc).Results:The median time between COVID-19 symptom onset and the interviews was 81 days(interquartile range:60-104).Of the 714 subjects,249(34.9%)reported total recovery of their chemosensory function;437(61.2%)had at least one treatment since the beginning of the *** and those with more comorbidities had undergone more *** recovery rates of the treated and nontreated groups did not differ ***,respondents who had used nitazoxanide tended to have a higher rate of self-reported taste or smell *** who took oral zinc were less likely to ***:No medication employed during the first months after sARs-CoV-2 infection had a clear positive effect on returning self-reported smell or taste function to normal,although nitrazoxide trended in a positive *** zinc had a negative effect on the reported recovery of these senses.

关键词： chemosensory disorder coronavirus infections COVID-19 drug therapy sARs-CoV-2 smell loss taste loss

A new perspective on intervertebral disc calcification—from bench to bedside

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Bone Research 2024年第1期12卷 50-61页

作者： Emanuel j.Novais Rajkishen Narayanan jose A.Canseco Koen van de Wetering Christopher K.Kepler Alan s.Hilibrand Alexander R.Vaccaro Makarand V.Risbud Department of Orthopaedic surgery Sidney Kimmel Medical CollegeThomas Jefferson UniversityPhiladelphiaPAUSA Unidade Local de saúde do Litoral Alentejano Orthopedic DepartmentSantiago do CacémPortugal Rothman Orthopedic Institute at Thomas jefferson University PhiladelphiaPAUSA

Disc degeneration primarily contributes to chronic low back and neck ***,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed *** these phenotypes,disc calcification is the least *** calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and ***,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative *** is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local *** studies in mouse models have provided a better understanding of the mechanisms underlying this *** is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP ***,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to ***,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation *** there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.

关键词： degeneration metabolism intervertebral

Collisionless shock acceleration of protons in a plasma slab produced in a gas jet by the collision of two laser-driven hydrodynamic shockwaves

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Matter and Radiation at Extremes 2024年第2期9卷 12-25页

作者： j.-R.Marquès L.Lancia P.Loiseau P.Forestier-Colleoni M.Tarisien E.Atukpor V.Bagnoud C.Brabetz F.Consoli j.Domange F.Hannachi P.Nicolaï M.salvadori B.Zielbauer LULI CNRSÉcole PolytechniqueCEASorbonne UniversitéInstitut Polytechnique de Paris91128 Palaiseau CedexFrance CEA DAMDIF91297 Arpajon CedexFrance UniversitéParis-saclay CEALMCE91680 Bruyères-le-ChatelFrance CENBG CNRS-IN2P3Universitéde Bordeaux33175 Gradignan CedexFrance GsI Helmholtzzentrum für schwerionenforschung GmbH Planckstraße 164291 DarmstadtGermany University of Darmstadt Schloßgartenstr.764289 DarmstadtGermany ENEA Fusion and Technologies for Nuclear safety Department C.R.FrascatiVia Enrico Fermi 45FrascatiRomeItaly CELIA Universitéde Bordeaux–CNRS–CEA33405 TalenceFrance UniversitéParis-saclay CEALIDYL91191 Gif-sur-YvetteFrance

We have recently proposed a new technique of plasma tailoring by laser-driven hydrodynamic shockwaves generated on both sides of a gas jet[Marquès et al.,*** 28,023103(2021)].In a continuation of this numerical work,we study experimentally the influence of the tailoring on proton acceleration driven by a high-intensity picosecond laser in three cases:without tailoring,by tailoring only the entrance side of the picosecond laser,and by tailoring both sides of the gas *** tailoring,the acceleration is transverse to the laser axis,with a low-energy exponential spectrum,produced by Coulomb *** the front side of the gas jet is tailored,a forward acceleration appears,which is significantly enhanced when both the front and back sides of the plasma are *** forward acceleration produces higher-energy protons,with a peaked spectrum,and is in good agreement with the mechanism of collisionless shock acceleration(CsA).The spatiotemporal evolution of the plasma profile is characterized by optical shadowgraphy of a probe *** refraction and absorption of this beam are simulated by post-processing 3D hydrodynamic simulations of the plasma *** with the experimental results allows estimation of the thickness and near-critical density of the plasma slab produced by tailoring both sides of the gas *** parameters are in good agreement with those required for CsA.

关键词： acceleration hydrodynamic collision

Enhancing Ulcerative Colitis Diagnosis:A Multi-Level Classification Approach with Deep Learning

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Computer Modeling in Engineering & sciences 2024年第7期140卷 1129-1142页

作者： Hasan j.Alyamani Department of Information systems Faculty of Computing and Information Technology in RabighKing Abdulaziz UniversityJeddah21589Saudi Arabia

The evaluation of disease severity through endoscopy is pivotal in managing patients with ulcerative colitis,a condition with significant clinical ***,endoscopic assessment is susceptible to inherent variations,both within and between observers,compromising the reliability of individual *** study addresses this challenge by harnessing deep learning to develop a robust model capable of discerning discrete levels of endoscopic disease *** initiate this endeavor,a multi-faceted approach is embarked *** dataset is meticulously preprocessed,enhancing the quality and discriminative features of the images through contrast limited adaptive histogram equalization(CLAHE).A diverse array of data augmentation techniques,encompassing various geometric transformations,is leveraged to fortify the dataset’s diversity and facilitate effective feature extraction.A fundamental aspect of the approach involves the strategic incorporation of transfer learning principles,harnessing a modified ResNet-50 *** augmentation,informed by domain expertise,contributed significantly to enhancing the model’s classification *** outcome of this research endeavor yielded a highly promising model,demonstrating an accuracy rate of 86.85%,coupled with a recall rate of 82.11%and a precision rate of 89.23%.

关键词： Ulcerative colitis deep learning CLAHE transfer learning geometric transformations

Intelligent Machine Learning Based Brain Tumor segmentation through Multi-Layer Hybrid U-Net with CNN Feature Integration

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Computers, Materials & Continua 2024年第4期79卷 1301-1317页

作者： sharaf j.Malebary Department of Information Technology Faculty of Computing and Information TechnologyKing Abdulaziz UniversityP.O.Box 344Rabigh21911Saudia Arabia

Brain tumors are a pressing public health concern, characterized by their high mortality and morbidity ***, the manual segmentation of brain tumors remains a laborious and error-prone task, necessitatingthe development of more precise and efficient methodologies. To address this formidable challenge, we proposean advanced approach for segmenting brain tumorMagnetic Resonance Imaging (MRI) images that harnesses theformidable capabilities of deep learning and convolutional neural networks (CNNs). While CNN-based methodshave displayed promise in the realm of brain tumor segmentation, the intricate nature of these tumors, markedby irregular shapes, varying sizes, uneven distribution, and limited available data, poses substantial obstacles toachieving accurate semantic segmentation. In our study, we introduce a pioneering Hybrid U-Net framework thatseamlessly integrates the U-Net and CNN architectures to surmount these challenges. Our proposed approachencompasses preprocessing steps that enhance image visualization, a customized layered U-Net model tailoredfor precise segmentation, and the inclusion of dropout layers to mitigate overfitting during the training ***, we leverage the CNN mechanism to exploit contextual information within brain tumorMRI images,resulting in a substantial enhancement in segmentation *** experimental results attest to the exceptionalperformance of our framework, with accuracy rates surpassing 97% across diverse datasets, showcasing therobustness and effectiveness of our approach. Furthermore, we conduct a comprehensive assessment of ourmethod’s capabilities by evaluating various performance measures, including the sensitivity, jaccard-index, andspecificity. Our proposed model achieved 99% accuracy. The implications of our findings are profound. Theproposed Hybrid U-Net model emerges as a highly promising diagnostic tool, poised to revolutionize brain tumorimage segmentation for radiologists and clinician

关键词： Brain tumor Hybrid U-Net CLAHE transfer learning MRI images

One-neutron stripping process in the^(209)Bi(^(6)Li,^(5)Li)^(210)Bi*reaction reaction

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Nuclear science and Techniques 2024年第6期35卷 120-129页

作者： Gao-Long Zhang Zhen-Wei jiao Guang-Xin Zhang E.N.Cardozo B.Paes shi-Peng Hu jian-Qiang Qian Daniele Mengoni Wei-Wei Qu Cong-Bo Li Yun Zheng Huan-Qiao Zhang Hui-Bin sun Nan Wang Chun-Lei Zhang j.j.Valiente-Dobón D.Testov M.Mazzocco A.Gozzelino C.Parascandolo D.Pierroutsakou M.La Commara A.Goasduff D.Bazzacco D.R.Napoli F.Galtarossa F.Recchia A.Illana s.Bakes I.Zanon s.Aydin Gde Angelis M.siciliano R.Menegazzo s.M.Lenzi s.Akkoyun L.F.Canto j.Lubian school of Physics Beihang UniversityBeijing 100191China sino-French Institute of Nuclear Engineering and Technology Sun Yat-Sen UniversityZhuhai 519082China Instituto de Física Universidade Federal Fluminense24210-340 NiteróiRio de JaneiroBrazil Laboratorio TANDAR Comisión Nacional de Energía AtómicaBKNA1650 San MartíınArgentina Institute for Advanced study in Nuclear Energy and safety Shenzhen UniversityShenzhen 518060China shenzhen Key Laboratory of Research and Manufacture of High Purity Germanium Materials and Fetectors Shenzhen UniversityShenzhen 518060China INFN Sezione di PadovaPaduaItaly Dipartimento di fisica Astronomia dell’Universita di padova PaduaItaly state Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and ProtectionSoochow UniversitySuzhou 215123China China Institute of Atomic Energy Beijing 102413China The Key Laboratory of Beam Technology and Material Modification of Ministry of Education College of Nuclear Science and TechnologyBeijing Normal UniversityBeijing 100875China Laboratori Nazionali di Legnaro INFN35020 LegnaroItaly INFN Sezione di Napoli80126 NaplesItaly Dipartimento di Farmacia Universitàdi Napoli“Federico II”80131 NaplesItaly Department of Natural and Mathematical sciences Faculty of EngineeringTarsus University33480 MersinTurkey Physics Division Argonne National LaboratoryLemontILUSA Department of Physics Sivas Cumhuriyet UniversitySivasTurkey Instituto de Física Universidade Federal do Rio de JaneiroRio de Janeiro CP 6852821941-972Brazil

One-neutron stripping process between^(6)Li and^(209)Bi was studied at 28,30,and 34 MeV using the in-beamγ-ray spectroscopy ***γ-γcoincident analysis clearly identified twoγ-rays feeding the ground and long-lived isomeric states,which were employed to determine the cross *** one-neutron stripping cross sections were similar to the cross sections of complete fusion in the^(6)Li+^(209)Bi system,but the one-neutron stripping cross sections decreased more gradually at the sub-barrier region.A coupled-reaction-channel calculation was performed to study the detailed reaction mechanism of the one-neutron stripping process in^(6)*** calculations indicated that the first excited state of 5 Li is critical in the actual one-neutron transfer mechanism,and the valence proton of 209Bi can be excited to the low-lying excited state in(^(6)Li,^(5)Li)reaction,unlike in the(d,p)reaction.

关键词： Transfer reaction Weakly bound nuclei Cross section