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Optimized RNA interference therapeutics combined with interleukin-2 mRNA for treating hepatitis B virus infection

Signal Transduction and Targeted Therapy 2024年第7期9卷 3063-3076页

作者： Wenjing Zai min Yang Kuan Jiang juan Guan Huijing Wang Kongying Hu Chao Huang Jieliang Chen Wei Fu Changyou Zhan Zhenghong Yuan Key Laboratory of medical molecular Virology(mOE/NHC/CAmS) Research Unit of Cure of Chronic Hepatitis B Virus Infection(CAMS)Shanghai Frontiers Science Center of Pathogenic Microbes and InfectionSchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghaiP.R.China Department of Pharmacology School of Basic Medical SciencesFudan UniversityShanghaiP.R.China Shanghai Engineering Research Center for Synthetic Immunology Fudan UniversityShanghaiP.R.China Eye Institute and Department of Ophthamology Eye and ENT HospitalFudan UniversityShanghaiP.R.China Pharmacy Department of Huashan Hospital Fudan UniversityShanghaiP.R.China Institute of Pediatric Translational medicine Shanghai Institute for Pediatric Congenital Heart DiseaseShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Institute of Infectious Disease and Biosecurity ShanghaiP.R.China

This study aimed to develop a pan-genotypic and multifunctional small interfering RNA(siRNA)against hepatitis B virus(HBV)with an efficient delivery system for treating chronic hepatitis B(CHB),and explore combined RNA interference(RNAi)and immune modulatory modalities for better viral *** synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed and *** lipid nanoparticle(LNP)formulation was optimized by adopting HO-PEG_(2000)-DmG lipid and modifying the molar ratio of traditional polyethylene glycol(PEG)lipid in LNP *** efficacy and safety of this formulation in delivering siHBV(tLNP/siHBV)along with the mouse IL-2(mIL-2)mRNA(tLNP/siHBVIL2)were evaluated in the rAAVHBV1.3 mouse model.A siRNA combination(terms“siHBV”)with a genotypic coverage of 98.55%was selected,chemically modified,and encapsulated within an optimized LNP(tLNP)of high efficacy and security to fabricate a therapeutic formulation for *** results revealed that tLNP/siHBV significantly reduced the expression of viral antigens and DNA(up to 3log_(10)reduction;vs PBS)in dose-and time-dependent manners at single-dose or multi-dose frequencies,with satisfactory safety *** studies showed that tLNP/siHBVIL2 enables additive antigenic and immune control of the virus,via introducing potent HBsAg clearance through RNAi and triggering strong HBV-specific CD4^(+)and CD8^(+)T cell responses by expressed mIL-2 *** adopting tLNP as nucleic acid nanocarriers,the co-delivery of siHBV and mIL-2 mRNA enables synergistic antigenic and immune control of HBV,thus offering a promising translational therapeutic strategy for treating CHB.

关键词： formulation enable offering

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Grain boundary engineering for enhancing intergranular damage resistance of ferritic/martensitic steel P92

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Nuclear Science and Techniques 2024年第5期35卷 186-199页

作者： Lei Peng Shang-ming Chen Jing-Yi Shi Yong-Jie Sun Yi-Fei Liu Yin-Zhong Shen Hong-Ya He Hui-juan Wang Jie Tian State Key Laboratory of Particle Detection and Electronics University of Science and Technology of ChinaHefei 230026China School of Nuclear Science and Technology University of Science and Technology of ChinaHefei 230027China School of materials Engineering Shanghai University of Engineering Science333 Long Teng RoadShanghai 201620China Experimental Center of Engineering and material Science University of Science and Technology of ChinaHefei 230026China

Ferritic/martensitic(F/m)steel is widely used as a structural material in thermal and nuclear power ***,it is susceptible to intergranular damage,which is a critical issue,under service *** this study,to improve the resistance to intergranular damage of F/m steel,a thermomechanical process(TmP)was employed to achieve a grain boundary engineering(GBE)microstructure in F/m steel *** TmP,including cold-rolling thickness reduction of 6%,9%,and 12%,followed by austenitization at 1323 K for 40 min and tempering at 1053 K for 45 min,was applied to the as-received(AR)P92 *** prior austenite grain(PAG)size,prior austenite grain boundary character distribution(GBCD),and connectivity of prior austenite grain boundaries(PAGBs)were *** to the AR specimen,the PAG size did not change *** fraction of coincident site lattice boundaries(CSLBs,3≤Σ≤29)and Σ3^(n) boundaries along PAGBs decreased with increasing reduction ratio because the recrystallization fraction increased with increasing reduction *** PAGB connectivity of the 6%deformed specimen slightly deteriorated compared with that of the AR ***,potentiodynamic polarization studies revealed that the intergranular damage resistance of the studied steel could be improved by increasing the fraction of CSLBs along the PAGBs,indicating that the TmP,which involves low deformation,could enhance the intergranular damage resistance.

关键词： Grain boundary engineering Ferritic/martensitic steel Prior austenite grain boundary character distribution Grain boundary connectivity Intergranular damage resistance

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Allosteric regulation of Keap1 by 8b-hydroxy-acyclocostunolide for the treatment of acute lung injury

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4174-4178页

作者： juan Zhang min Zhang Qi-meng Zhu Xin-Rong Xu Yan-Li Feng Sheng Lin Feng Qiu Cheng-Peng Sun School of Chinese materia medic1 Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese MedicineTianjin University of Traditional Chinese MedicineTianjin 301617China Key Laboratory of Chinese Internal medicine of ministry of Education and Beijing Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China

To the Editor:Acute lung injury(ALI)is a debilitating lung disease characterized by pulmonary edema,diffuse alveolar damage,and uncontrolled neutrophil *** cases of ALI can potentially lead to the development of acute respiratory distress syndrome(ARDS),which can lead to impaired respiratory function,multiorgan dysfunction,and an extremely high mortality *** may be caused by various factors,including aspiration,severe pneumonia,sepsis,trauma,fatty embolism,pancreatitis,and blood *** clinical approaches to treating ALI/ARDS include mechanical ventilation,extracorporeal membrane oxygenation(ECmO),and other supportive therapies5,***,ALI/ARDS is an urgent problem that needs to be addressed in the field of respiratory critical care and innovative mechanisms and therapies6.

关键词： macrophage overactivation Keap1 8b-Hydroxy-a-cyclocostunolide Nrf2 Acute lung injury

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metal-metal bonds in Zintl clusters:Synthesis,structure and bonding in[Fe_(2)Sn_(4)Bi_(8)]^(3-)and[Cr_(2)Sb_(12)]^(3-)

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Chinese Chemical Letters 2024年第8期35卷 558-566页

作者： Ya-Nan Yang Zi-Sheng Li Sourav mondal Lei Qiao Cui-Cui Wang Wen-juan Tian Zhong-ming Sun John E.mcGrady State Key Laboratory of Element-Organic Chemistry Tianjin Key Lab for Rare Earth Materials and ApplicationsSchool of Materials Science and EngineeringNankai UniversityTianjin 300350China Department of Chemistry University of OxfordInorganic Chemistry LaboratoryOxfordOX13QRUnited Kingdom

We report here the synthesis and characterization of two new members of the m2 E 12 family of endohe-dral Zintl clusters,[Fe_(2)Sn_(4)Bi_(8)]^(3-)and[Cr_(2)Sb_(12)]^(3-),both of which contain open-shell metal dimers encap-sulated inside a triple-decker cluster of main-group *** 75-electron[Fe_(2)Sn_(4)Bi_(8)]^(3-)cluster has a D4h-symmetric structure,while[Cr_(2)Sb_(12)]^(3-),despite having the same 75-electron count,is strongly dis-torted to a geometry that resembles a CrSb_(8)crown capped by a CrSb_(4)*** structural differences between the two are driven by the increasing availability of 3d electron density in the earlier transi-tion metal,which leads,ultimately,to different electronic configurations in the two *** trends precisely mirror those observed in the mE_(10)and mE_(12)families containing a single transition metal ion.

关键词： Zintl anions Endohedral clusters metal-metal bond Second-order Jahn-Teller effect DFT calculation

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Debaryomyces hansenii supplementation in low fish meal diets promotes growth,modulates microbiota and enhances intestinal condition in juvenile marine fish

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Journal of Animal Science and Biotechnology 2024年第1期15卷 253-276页

作者： Ignasi Sanahuja Alberto Ruiz Joana P.Firmino Felipe E.Reyes-López juan B.Ortiz-Delgado Eva Vallejos-Vidal Lluis Tort Dariel Tovar-Ramírez Isabel m.Cerezo miguel A.moriñigo Carmen Sarasquete Enric Gisbert Aquaculture Program Institute of Agrifood Research and Technology(IRTA)La Rapita 43540Spain Centro de Biotecnologia Acuicola Universidad de Santiago de ChileSantiagoChile Instituto de Ciencias marinas de Andalucia(ICmAN-CSIC) Avda.Republica Saharaui no 2Campus Universitario Rio San PedroPuerto RealCadiz 11510Spain Nucleo de Investigaciones Aplicadas en Ciencias Veterinarias y Agronomicas Facultad de Medicina Veterinaria y AgronomiaUniversidad de Las AmericasSantiagoChile Department of Cell Biology Physiologyand ImmunologyUniversitat Autonoma de BarcelonaBarcelonaSpain Centro de Investigaciones Biologicas del Noroeste SC CIBNORLa PazMexico Department of microbiology Instituto de Biotecnologia Y Desarrollo Azul(IBYDA)Faculty of SciencesUniversity of Malaga29010 MalagaSpain SCBI Bioinformatic UnitUniversity of Malaga29590 MalagaSpain

Background The development of a sustainable business model with social acceptance,makes necessary to develop new strategies to guarantee the growth,health,and well-being of farmed *** hansenii is a yeast species that can be used as a probiotic in aquaculture due to its capacity to i)promote cell proliferation and differen-tiation,ii)have immunostimulatory effects,iii)modulate gut microbiota,and/or iv)enhance the digestive *** provide inside into the effects of *** on juveniles of gilthead seabream(Sparus aurata)condition,we inte-grated the evaluation of the main key performance indicators coupled with the integrative analysis of the intestine condition,through histological and microbiota state,and its transcriptomic *** After 70 days of a nutritional trial in which a diet with low levels of fishmeal(7%)was supplemented with 1.1%of ***(17.2×10^(5) CFU),an increase of ca.12%in somatic growth was observed together with an improve-ment in feed conversion in fish fed a yeast-supplemented *** terms of intestinal condition,this probiotic modu-lated gut microbiota without affecting the intestine cell organization,whereas an increase in the staining intensity of mucins rich in carboxylated and weakly sulphated glycoconjugates coupled with changes in the affinity for certain lectins were noted in goblet *** in microbiota were characterized by the reduction in abundance of several groups of Proteobacteria,especially those characterized as opportunistic *** microarrays-based transcrip-tomic analysis found 232 differential expressed genes in the anterior-mid intestine of ***,that were mostly related to metabolic,antioxidant,immune,and symbiotic *** Dietary administration of *** enhanced somatic growth and improved feed efficiency param-eters,results that were coupled to an improvement of intestinal condition as histochemical and transcriptomic tools *** probiotic ye

关键词： Debaryomyces hansenii Intestine condition Low fish meal diet microbiota Transcriptomics Yeast probiotic

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Application of Global Leadership Initiative on malnutrition criteria in patients with liver cirrhosis

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Chinese medical Journal 2024年第1期137卷 97-104页

作者： minjie Jiang juan Chen muchen Wu Jing Wu Xiaotong Xu juan Li Can Liu Yaping Zhao Xin Hua Qinghua meng Department of Hepatology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Beijing Institute of Hepatology Beijing 100069China Department of medical Oncology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Department of Nutrition Beijing You-An HospitalCapital Medical UniversityBeijing 100069China

Background:The Global Leadership Initiative on malnutrition(GLIm)criteria were published to build a global consensus on nutritional *** muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIm consensus ***,there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical *** study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIm-defined malnutrition,as well as the prevalence of GLIm-defined malnutrition in hospitalized cirrhotic ***:This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1,2018,and February 28,2022,at Beijing You-An Hospital,Capital medical *** patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography(CT)examination during hospitalization were included in the *** patients were randomly divided into a modeling group(cohort 1,667 patients)and a validation group(cohort 2,335 patients).In cohort 1,optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index(L3-SmI)were determined using receiver operating characteristic analyses against in-hospital mortality in different gender ***,patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002(NRS-2002),and malnutrition was diagnosed by GLIm ***,the reference values of reduced muscle mass in GLIm criteria were derived from the L3-SmI values from cohort *** logistic regression analysis was used to analyze the association between GLIm-defined malnutrition and clinical ***:The optimal cut-off values of L3-SmI were 39.50 cm 2/m 2 for male patients and 33.06 cm 2/m 2 for female *** on the cut-off values,31.63%(68/215)of the male patients and 23.3%(28/120)of the female patients had CT-determ

关键词： malnutrition Liver cirrhosis Sarcopenia Clinical outcomes GLIm criteria

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Effects of Al_(2)O_(3)-SiO_(2) Raw material Types on Properties of Anorthite Based Insulation Refractories

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China's Refractories 2024年第1期33卷 23-27页

作者： DU juan GUO Huishi YANG Jialin LI Wenfeng GUI Yanghai ZHAO Zhiqiang LIU Yingfan School of materials Science and Engineering Henan University of TechnologyZhengzhou 450001China School of materials and Chemical Engineering Zhengzhou University of Light IndustryZhengzhou 450051China

To optimize their Al_(2)O_(3)-SiO_(2) raw materials,anorthite based insulation refractories were prepared by the in-situ sintering process combined with the foaming method after sintering at 1350℃for 3 h,using green and pollution-free kaolin,kyanite,andalusite and sillimanite as Al_(2)O_(3)-SiO_(2) raw materials,respectively,and industrial CaCO_(3) as the CaO *** of Al_(2)O_(3)-SiO_(2) raw material types on the physical properties,phase composition and microstructure were *** results are as *** samples prepared by different Al_(2)O_(3)-SiO_(2) raw materials have hexagonal flake anorthite and a small amount of mullite and *** bulk density and thermal conductivity decrease in the order of using kaolin,andalusite,kyanite and sillimanite as the Al_(2)O_(3)-SiO_(2) raw material,but their apparent porosity ***,in the sample with kaolin,the bonding between anorthite crystals on the pore walls is closer than that of the other samples,which is conducive to increasing the cold crushing *** bonding between anorthite crystals on pore walls gradually decreases in the order of using kyanite,andalusite and sillimanite as the Al_(2)O_(3)-SiO_(2) raw material,thus their cold crushing strength decreases *** comprehensive consideration,the properties of the sample from kyanite are the *** apparent porosity,thermal conductivity and cold crushing strength are 84.6%,0.141 W·m^(-1)·K^(-1) and 1.89 mPa,respectively.

关键词： anorthite based insulation refractories Al_(2)O_(3)-SiO_(2)raw materials crushing strength thermal conductivity microstructure

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Paleoenvironmental changes recorded by grain size of loess/paleosol sequence from the Chifeng City, Northeastern China since the Last Glacial

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Journal of mountain Science 2024年第09期 3068-3082页

作者： LI juan BRYE Kristofor R. ZHANG mengge JIANG Zhuodong WANG Qiubing College of Land and Environment Shenyang Agricultural University Department of Crop Soil and Environmental Sciences University of Arkansas

The accumulation processes of loess in northeastern（NE） China record the varying characteristics of the East Asian monsoons（EAm） and the evolution of the local *** this study,grain size end-member analysis of the Dajiugang（DJG） section deposited since the Last Glacial in Chifeng City,NE China was used to reveal the dynamic depositional characteristics of loess and environmental evolution of NE *** showed that the Chifeng loess comprises three grain size endmembers（Em）,Em1（7.38 μm）,Em2（49.4 μm） and Em3（90.00 μm）,indicating the three transport dynamics of dust delivered to the *** Em1represents atmospheric dust as the *** Em2,mainly derived from relatively distant-sources deposition,and Em3,material transported over a short distance,correspond to the intensity of southwesterly winds and the East Asian Winter monsoon（EAWm）,*** of climate reconstruction,combined with other records,showed that the climate was generally cold and dry with a strong EAWm and a weak East Asian summer monsoon（EASm） during the stadial-period [marine Isotope Stage（mIS）4and mIS2stage].The climate was predominantly warm and humid,with weak EAWm and surface winds and strong EASm in interstadial-period（mIS3and mIS1stage）.Comparisons between indicators,e.g.,Em3,the LR04 benthic δ18O stack and summer insolation at65°N suggest that the strong EAWm is induced by increasing the Northern Hemisphere ice volume and reduced summer solar radiation.

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Textured Asymmetric membrane Electrode Assemblies of Piezoelectric Phosphorene and Ti_(3)C_(2)T_(x)mXene Heterostructures for Enhanced Electrochemical Stability and Kinetics in LIBs

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Nano-micro Letters 2024年第4期16卷 394-414页

作者： Yihui Li juan Xie Ruofei Wang Shugang min Zewen Xu Yangjian Ding Pengcheng Su Xingmin Zhang Liyu Wei Jing‑Feng Li Zhaoqiang Chu Jingyu Sun Cheng Huang Volta and DiPole materials Labs College of EnergySoochow Institute for Energy and Materials InnovationS(SIEMIS)Key Laboratory of Advanced Carbon Materials and Wearable Energy Technologies of Jiangsu ProvinceKey Laboratory of Core Technology of High Specific Energy Battery and Key Materials for Petroleum and Chemical IndustrySoochow UniversitySuzhou 215006People’s Republic of China School of materials Science and Engineering Jiangsu UniversityZhenjiang 212013People’s Republic of China College of Underwater Acoustic Engineering Harbin Engineering UniversityHarbin 150001People’s Republic of China Shanghai Synchrotron Radiation Facility Shanghai Advanced Research InstituteShanghai Institute of Applied PhysicsChinese Academy of SciencesShanghai 201204People’s Republic of China State Key Laboratory of New Ceramics and Fine Processing School of Materials Science and EngineeringTsinghua UniversityBeijing 100084People’s Republic of China High Density materials Technology Center for Flexible Hybrid Electronics Suzhou Institute of Electronic Functional Materials TechnologySuzhou Industrial Technology Research InstituteSuzhou 215151People’s Republic of China Institute of Advanced materials and Institute of membrane Science and Technology Jiangsu National Synergistic Innovation Center for Advanced MaterialsSuzhou Laboratory and Nanjing Tech UniversityNanjing 211816People’s Republic of China

Black phosphorus with a superior theoretical capacity(2596 mAh g^(-1))and high conductivity is regarded as one of the powerful candidates for lithium-ion battery(LIB)anode materials,whereas the severe volume expansion and sluggish kinetics still impede its applications in *** contrast,the exfoliated two-dimensional phosphorene owns negligible volume variation,and its intrinsic piezoelectricity is considered to be beneficial to the Li-ion transfer kinetics,while its positive influence has not been discussed ***,a phosphorene/mXene heterostructure-textured nanopiezocomposite is proposed with even phosphorene distribution and enhanced piezo-electrochemical coupling as an applicable free-standing asymmetric membrane electrode beyond the skin effect for enhanced Li-ion *** experimental and simulation analysis reveals that the embedded phosphorene nanosheets not only provide abundant active sites for Li-ions,but also endow the nanocomposite with favorable piezoelectricity,thus promoting the Li-ion transfer kinetics by generating the piezoelectric field serving as an extra *** waltzing with the mXene framework,the optimized electrode exhibits enhanced kinetics and stability,achieving stable cycling performances for 1,000 cycles at 2 A g^(-1),and delivering a high reversible capacity of 524 m Ah g^(-1)at-20℃,indicating the positive influence of the structural merits of self-assembled nanopiezocomposites on promoting stability and kinetics.

关键词： Phosphorene Nanopiezocomposite Piezo-electrochemical coupling membrane electrode assembly Lithium-ion storage

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Organ Abscission in Plants: With Special Emphasis on Bell Pepper

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Phyton-International Journal of Experimental Botany 2024年第7期93卷 1467-1484页

作者： Ramiro Reyes-Castro Héctor G.Núñez-Palenius juan I.Valiente-Banuet maría E.Sosa-morales Blanca E.Orosco-Alcalá Rafael Guzmán-mendoza Graciela m.L.Ruiz-Aguilar Rogelio Costilla-Salazar Life Sciences Division Universidad de GuanajuatoIrapuato36500México School of Engineering and Sciences Tecnologico de MonterreyQuerétaro76130México

Bell pepper(Capsicum annuum L.),along with potato and tomato,is one of the three most cultivated vegetables in the *** pepper is worldwide accepted due to its characteristics of color,smell,ﬂavor,and *** pepper is also considered a nutritious food due to its vitamin and antioxidant *** mexico,bell pepper production has a high value because it is grown for the international markets,particularly the United States of ***,the abscission ofﬂowers and fruits is a factor that limits the yield,hinders the planning of activities,and causes a variation in the prices of *** to the importance of this process,in this work we did a bibliometric analysis and literature review of scientiﬁc advances for the understanding of the abscission pro-cess in plants,and in particular for the bell ***,we introduce new perspectives that would help direct future research about organ abscission in ***,the lack of research that would further clarify abscis-sion process in the bell pepper plant is discussed.

关键词： Capsicum annuum abscission zone plant growth regulators environmental factors

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