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A SARS-CoV-2-specific CAR-T-cell model identifies felodipine,fasudil,imatinib,and caspofungin as potential treatments for lethal COVID-19

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Cellular & Molecular Immunology 2023年第4期20卷 351-364页

作者： in Xia lun-zhi yuan Ya-hong Hu Jun-yi Liu Guo-sheng Hu Ruo-yao Qi Tian-ying Zhang Hua-long Xiong Zao-zao Zheng Hong-wei Lin Jia-mo Zhang Chao Yu Ming Zhou Jian Ma Tong Cheng Ri-rong Chen Yi Guan Ning-shao Xia Wen Liu State Key Laboratory of Cellular Stress Biology School of Pharmaceutical SciencesXiamen UniversityXiang’an South RoadXiamenFujian 361102China Fujian Provincial Key Laboratory of Innovative Drug Target Research School of Pharmaceutical SciencesXiamen UniversityXiang’an South RoadXiamenFujian 361102China State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Life SciencesSchool of Public HealthXiamen UniversityXiang’an South RoadXiamenFujian 361102China State Key Laboratory of Emerging Infectious Diseases School of Public HealthLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019(COVID-19)severity and lethality.However,drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed.Here,we constructed a SARS-CoV-2 spike protein-specific CAR,and human T cells infected with this CAR(SARS-CoV-2-S CAR-T)and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients,causing cytokine storm and displaying a distinct memory,exhausted,and regulatory T-cell phenotype.THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture.Based on this"two-cell"(CAR-T and THP1 cells)model,we screened an FDA-approved drug library and found that felodipine,fasudil,imatinib,and caspofungin were effective in suppressing the release of cytokines,which was likely due to their ability to suppress the NF-kB pathway in vitro.Felodipine,fasudi,imatinib,and caspofungin were further demonstrated,although to different extents,to attenuate lethal inflammation,ameliorate severe pneumonia,and prevent mortality in a SARS-CoV-2-infected Syrian hamster model,which were also linked to their suppressive role in inflammation.In summary,we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner.The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe,inexpensive,and easily accessible for immediateuseinmostcountries.

关键词： COVID-19 SARS-CoV-2 CAR-T anti-inflammation NF-kB pathway

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Synergic action of linear dispersion, second-order nonlinearity, and third-order nonlinearity in shaping the spectral profile of a femtosecond pulse transporting in a lithium niobate crystal

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Photonics Research 2024年第4期12卷 774-783页

作者： LIHONG HONG yuanyuan LIU zhi-yuan LI State Key Laboratory of High Field Laser Physics Shanghai Institute of Optics and Fine MechanicsChinese Academy of SciencesShanghai 201800China School of Physics and Optoelectronics South China University of TechnologyGuangzhou 510640China

We present a detailed theoretical and numerical analysis on the temporal-spectral-spatial evolution of a highpeak-power femtosecond laser pulse in two sets of systems:a pure lithium niobate(LN)plate and a periodically poled lithium niobate(PPLN)plate.We develop a modified unidimensional pulse propagation model that considers all the prominent linear and nonlinear processes and carried out the simulation process based on an improved split-step Fourier transformation method.We theoretically analyze the synergic action of the linear dispersion effect,the second-order nonlinearity(2nd-NL)second-harmonic generation(SHG)effect,and the third-order nonlinearity(3rd-NL)self-phase modulation(SPM)effect,and clarify the physical mechanism underlying the peculiar and diverse spectral broadening patterns previously reported in LN and PPLN thin plate experiments.Such analysis and discussion provides a deeper insight into the synergetic contribution of these linear and nonlinear effects brought about by the interaction of a femtosecond laser pulse with the LN nonlinear crystal and helps to draw a picture to fully understand these fruitful optical physical processes,phenomena,and laws.

关键词： pulse nonlinearity lithium

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Single-atom Ag-loaded carbon nitride photocatalysts for efficient degradation of acetaminophen:The role of Ag-atom and O_(2)

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Journal of Environmental Sciences 2024年第5期139卷 12-22页

作者： Yi yuan Wen-Long Wang zhi-Wei Wang Jin Wang Qian-yuan Wu Key Laboratory of Microorganism Application and Risk Control of Shenzhen Guangdong Provincial Engineering Research Center for Urban Water Recycling and Environmental SafetyInstitute of Environment and EcologyShenzhen International Graduate SchoolTsinghua UniversityShenzhen 518055China Shenzhen Environmental Science and New Energy Technology Engineering Laboratory Tsinghua-Berkeley Shenzhen InstituteShenzhen 518055China College of Materials Science and Engineering Shenzhen UniversityShenzhen 518071China

Carbon nitride has been extensively used as a visible-light photocatalyst,but it has the disadvantages of a low specific surface area,rapid electron-hole recombination,and relatively low light absorbance.In this study,single-atom Ag was successfully anchored on ultrathin carbon nitride(UTCN)via thermal polymerization,the catalyst obtained is called AgUTCN.The Ag hardly changed the carbon nitride's layered and porous physical *** exhibited efficient visible-light photocatalytic performances in the degradation of various recalcitrant pollutants,eliminations of 85% were achieved by visible-light irradiation for 1hr.Doping with Ag improved the photocatalytic performance of UTCN by narrowing the forbidden band gap from 2.49 to 2.36 e V and suppressing electron-hole pair recombination.In addition,Ag doping facilitated O_(2) adsorption on UTCN by decreasing the adsorption energy from -0.2 to -2.22 e V and favored the formation of O_(2)^(·-).Electron spin resonance and radical-quenching experiments showed that O_(2)^(·-)was the major reactive species in the degradation of Acetaminophen(paracetamol,APAP).

关键词： Ag single atom Carbon nitride Photocatalysis Visible light Adsorption energy Reactive species

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Microstructure and mechanical properties of Ti/Al/Ti clad plates prepared via powder-in-tube method

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Journal of Iron and Steel Research(International) 2024年第3期31卷 670-687页

作者： Xian-lei Hu Qin-cheng Xie Yi yuan Ying zhi State Key Laboratory of Rolling and Automation Northeastern UniversityShenyang 110819LiaoningChina Suzhou Dongbao Haixing Metal Material Technology Co. Ltd.Suzhou 215600JiangsuChina School of Material Science and Engineering Northeastern UniversityShenyang 110819LiaoningChina

The Ti/Al/Ti clad plates exhibit a broad spectrum of potential applications.However,the conventional techniques of hot-pressing composite and explosive composite are intricate and environmentally hazardous.A novel method was introduced for preparing clad plates,namely,the powder-in-tube method.This method involves a combination of cold rolling,annealing at a temperature of 550℃,and double rolling.The morphology of the intermetallic compound layer was analyzed through the utilization of interface stripping test,tensile test,and microscopic characterization.The interface morphology,interface bonding properties,tensile fracture structures,and properties of plates under the first and second rolling were compared,along with the effects of intermetallic compounds on the interface properties.The results indicate that the powder-in-tube method,when annealed at 550℃,can produce a composite plate featuring a complete and uniform Ti/Al interface.The obtained plate exhibits a peeling strength of 21.5 N/mm,tensile strength of 424 MPa,and elongation of 11.5%.Furthermore,a systematic analysis was conducted to determine the causes of performance degra-dation observed during annealing at temperatures of 600 and 650℃.

关键词： Powder-in-tube method-Ti/Al/Ti clad plate Annealing Cold rolling-Mechanical property

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Multi-physical fields distribution in billet during helical electromagnetic stirring:A numerical simulation research

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China Foundry 2024年第1期21卷 51-59页

作者： Dong Pan Qing-tao Guo Kai-lun Zhang Fu-zhi Yu Yu-ying Li Yu-bao Xiao State Key Laboratory of Metal Materials for Marine Equipment and Application Anshan 114009LiaoningChina Ansteel Beijing Research Institute Co. Ltd.Beijing 102200China

Electromagnetic stirring is one of the widely applied techniques to modify the quality of casting billets.Different from conventional rotate stirring,the helical stirring is more professional in assisting multi-dimensional flow of molten metal and eliminating solidification defects.In this study,the single-winding helical stirring(SWHS)was introduced,offering advantages such as smaller volume and lower electromagnetic shielding compared to traditional helical stirring methods.Following a comprehensive numerical simulation,the stirring parameters of SWHS were adjusted to yoke inclination angle of 43°and frequency of 12 Hz.The higher electromagnetic force and flow velocity in drawing direction,as well as the lower temperature gradient induced by the SWHS,are positive factors for homogeneous solidification of billet.The experimental results on Al-8%Si alloy and 0.4%C-1.1%Mn steel demonstrate that compared to rotate stirring,the SWHS process can induce better billet quality and is more effective in accelerating the equiaxed expansion and reducing element segregation.The SWHS process can enhance the equiaxed ratio of the billet by 58.3%and reduce segregation degree of carbon element by 10.97%.Consequently,SWHS holds great promise as a potential approach for improving the quality of continuous casting billets.

关键词： billet electromagnetic stirring helical solidification element segregation numerical simulation

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Low interleukin-10 level indicates a good prognosis in Salmonella enterica serovar typhimurium-induced pediatric hemophagocytic lymphohistiocytosis:A case report

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World Journal of Clinical Cases 2024年第9期12卷 1660-1668页

作者： yuan-yuan Chen Xiang-zhi Xu Xiao-Jun Xu Division/Center of Pediatric Hematology Oncology Children’s HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina Pediatric Intensive Care Unit Children’s Hospital of Zhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

BACKGROUND Secondary hemophagocytic lymphohistiocytosis(sHLH)triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients.There is no consensus on how to treat S.typhimurium-triggered sHLH.CASE SUMMARY A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S.typhimurium,human rhinovirus,and Mycoplasma pneumoniae infections.At the time of admission to our institution,the patient’s T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6(IL-6),9.1 pg/mL for IL-10,and 246.7 pg/mL for interferon-gamma(IFN-γ),for which the ratio of IL-10 to IFN-γwas 0.04.In this study,the patient received meropenem,linezolid,and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy(10 mg/kg/d for 3 d)and antishock supportive treatment twice.After careful evaluation,this patient did not receive HLH chemotherapy and recovered well.CONCLUSION S.Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ≤1.33,an IL-10 concentration≤10.0 pg/mL,and/or an IFN-γconcentration≤225 pg/mL at admission.Early antimicrobial and supportive treatment was sufficient,and the HLH-94/2004 protocol was not necessary under these conditions.

关键词： Hemophagocytic lymphohistiocytosis Cytokine pattern Interferon gamma Interleukin-10 Salmonella enterica serovar Typhimurium Case report

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Pancreatic giant malignancy simulating a gastrointestinal stromal tumor

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 431-433页

作者： Ben-Jie Liu Chen-Hui Jin Yan-lun Guo zhi-Gang Ke Jun-Jun Huang Lin-Ping Cao Department of Hepatobiliary Surgery Department of General SurgeryPujiang Branch of the First Affiliated HospitalZhejiang University School of MedicineJinhua 322200China Department of Pathology Pujiang Branch of the First Affiliated HospitalZhejiang University School of MedicineJinhua 322200China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Pancreatic acinar cell carcinoma(PACC)is a rare malignant tumor of pancreatic epithelial cells,which produces pancreatic exocrine enzymes.PACC originates from acinar cells and terminal branches of the pancreatic ducts in the exocrine tissue of the pancreas.PACC accounts for 1%−2%of pancreatic exocrine tumors[1].Herein,we present an elderly woman with PACC who recovered after effective laparoscopic surgery.The tumor was located on the left side of the abdomen;imaging suggested that it was a gastrointestinal stromal tumor of the gastric wall origin,infiltrating the tail of the pancreas and omentum,while postoperative pathology suggested PACC.

关键词： Pancreatic gastrointestinal pancreas

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Moyamoya syndrome may result from psoriasis: Four case reports

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World Journal of Clinical Cases 2024年第10期12卷 1830-1836页

作者： zhi-Ying Chen Xiao-Qin Yu yuan-yuan Xiang Ling-Hua Liu Xiao-Ping Yin Department of Neurology The Affiliated Hospital of Jiujiang UniversityJiujiang 332000Jiangxi ProvinceChina Department of Dermatology The Affiliated Hospital of Jiujiang UniversityJiujiang 332000Jiangxi ProvinceChina

BACKGROUND Moyamoya syndrome(MMS)is a group of diseases that involves more than one underlying disease and is accompanied by moyamoya vascular phenomena.Psoriasis is a chronic immune skin disease closely linked to high blood pressure and heart disease.However,psoriasis-related MMS has not been reported.CASE SUMMARY We collected data on patients with stroke due to MMS between January 2017 and December 2019 and identified four cases of psoriasis.Case histories,imaging,and hematological data were collected.The average age of the initial stroke onset was 58.25±11.52 years;three cases of hemorrhagic and one case of ischemic stroke were included.The average duration from psoriasis confirmation to the initial MMS-mediated stroke onset was 17±3.56 years.All MMS-related stenoses involved the bilateral cerebral arteries:Suzuki grade III in one case,grade IV in two cases,and grade V in one case.Abnormally elevated plasma interleukin-6 levels were observed in four patients.Two patients had abnormally elevated immunoglobulin E levels,and two had thrombocytosis.All four patients received medication instead of surgery.With an average follow-up time of 2 years,two causing transient ischemic attacks occurred in two patients,and no hemorrhagic events occurred.CONCLUSION Psoriasis may be a potential risk factor for MMS.Patients with psoriasis should be screened for MMS when they present with neurological symptoms.

关键词： Moyamoya syndrome Psoriasis Stroke Interleukin-6 Immune Hypertension Case report

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Dry eye disease in systemic lupus erythematosus: a cross sectional study

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1255-1261页

作者： Sui-Fang Kang Ying-Xue Wang Qi-Chen Zhang zhi-lun Wang Guo-Ling Chen Department of Ophthalmology the Second Hospital of Shandong UniversityJinan 250033Shandong ProvinceChina Department of Rheumatology the Second Hospital of Shandong UniversityJinan 250033Shandong ProvinceChina

AIM:To explore ocular surface manifestations of dry eye disease(DED)and its influencing factors in systemic lupus erythematosus(SLE)patients.METHODS:Ophthalmological examinations were conducted in SLE patients(n=43)and controls(n=41),including Ocular Surface Disease Index(OSDI),objective scatter index(OSI),tear meniscus height(TMH),lipid layer thickness(LLT),non-invasive Keratograph tear breakup time(NIKBUT),corneal fluorescein score(CFS),Schirmer I test.DED was diagnosed according to the Tear Film and Ocular Surface Society Dry Eye Workshop II Criteria.SLE patients were further divided into DED group and non-DED group,the disease activity,clinical manifestations and laboratory investigations were compared between the two groups.The disease activity was evaluated by Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K).Receiver operative characteristic(ROC)curve and multiplefactor binary logistic regression were performed.RESULTS:SLE patients showed higher OSDI[9.1(2.8-15.9)vs 6.3(2.2-7.5),P=0.035],higher OSI[1.67(1.09-2.60)vs 0.96(0.87-1.60),P=0.001],higher CFS[1(0-2)vs 0(0-1),P=0.001],lower LLT[65(42-100)vs 100(79.5-100),P=0.010],and lower NIKBUT[8.03(4.02-9.73)vs 9.67(5.26-12.71),P=0.030]than controls.The 32.6%of SLE patients had DED,which was higher than 12.2%of healthy controls.DED group showed higher SLEDAI-2K score[9.7±6.1 vs 5.4±3.4,P=0.025],higher anti-cardiolipin antibody(ACL)[8.7(3.5-13.2)vs 3.6(2.0-6.9),P=0.035],and higher proportion of patients with cutaneous eruption[42.9%vs 6.9%,P=0.015]than non-DED group.According to multiple-factor binary logistic regression analysis,the SLEDAI-2K score(OR=1.194,P=0.041)and cutaneous eruption(OR=7.094,P=0.045)could be consider as risk factors for DED in SLE patients.The ROC curve of the combined factors including age,disease duration,SLEDAI-2K score,ACL,and cutaneous eruption was analyzed,with a sensitivity of 0.786,a specificity of 0.793,and an area under curve of 0.820.CONCLUSION:Ocular surface affection is frequent in SLE patients,and patients wi

关键词： autoimmune disease systemic lupus erythematosus dry eye disease

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Loss of heterozygosity for chromosomes 16q in Wilms tumors predicts outcomes:A meta-analysis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2159-2167页

作者： yuan-Hua Song Wen-Ling Li Zhen Yang Yan Gao zhi-Ping Feng Department of Oncology Kunming Children's HospitalKunming 650103Yunnan ProvinceChina Department of Nuclear Medicine The Third Affiliated Hospital of Kunming Medical University(Yunnan Cancer Hospital)Kunming 650118Yunnan ProvinceChina

BACKGROUND The research findings suggest that the prognosis of children with Wilms tumor(WT)is affected by various factors.Some scholars have indicated that loss of heterozygosity(LOH)on chromosome 16q is associated with a poor prognosis in patients with WT.AIM To further elucidate this relationship,we conducted a meta-analysis.METHODS This meta-analysis was registered in INPLASY(INPLASY2023100060).We systematically searched databases including Embase,PubMed,Web of Science,Cochrane,and Google Scholar up to May 31,2020,for randomized trials reporting any intrapartum fetal surveillance approach.The meta-analysis was performed within a frequentist framework,and the quality and network inconsistency of trials were assessed.Odds ratios and 95%CIs were calculated to report the relationship between event-free survival and 16q LOH in patients with WT.RESULTS Eleven cohort studies were included in this meta-analysis to estimate the relationship between event-free survival and 16q LOH in patients with WT(I^(2)=25%,P<0.001).As expected,16q LOH can serve as an effective predictor of eventfree survival in patients with WT(risk ratio=1.95,95%CI:1.52–2.49,P<0.001).CONCLUSION In pediatric patients with WT,there exists a partial correlation between 16q LOH and an unfavorable treatment prognosis.Clinical detection of 16q chromosome LOH warrants increased attention to the patient’s prognosis.

关键词： Loss of heterozygosity Wilms tumor Survival time Chromosomes 16q

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