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Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

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World Journal of Gastroenterology 2024年第5期30卷 471-484页

作者： Hui Hua Qian-Qian Zhao Miriam Nkesichi Kalagbor Guo-Zhi Yu Man Liu Zheng-Rui Bian Bei-Bei Zhang Qian Yu Yin-Hai Xu Ren-Xian Tang Kui-Yang Zheng Chao Yan Jiangsu Key Laboratory of immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Demonstration Center for Experimental Basic Medical Science EducationLaboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina Department of Laboratory Medicine The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221002Jiangsu ProvinceChina

BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment *** adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been *** To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing *** A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC *** sacrifice,the liver and the serum were collected from each *** hepatobiliary injuries,hepatic inflammation and fibrosis were *** targets of let-7a-5p and downstream molecule NF-κB were detected using Western *** rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 *** reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary ***,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic *** Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.

关键词： Primary sclerosing cholangitis Recombinant adeno-associated virus 8 Let-7a-5p Therapeutic effects Inflammation

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Targeting Haemaphysalis longicornis serpin to prevent tick feeding and pathogen transmission

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Insect Science 2024年第3期31卷 694-706页

作者： Tingting Feng Hao Tong Qianqian Zhang Zhihao Ming Zhenyu Song Xia Zhou Jianfeng Dai Institute of biology and Medical Sciences Jiangsu Key Laboratory of Infection and ImmunitySoochow UniversitySuzhouJiangsu ProvinceChina School of biology and Basic Medical Science Suzhou Medical College of Soochow UniversitySuzhouJiangsu ProvinceChina

Serine proteinase inhibitors(serpins),identified from the hard tick Haemaphysalis longicornis of China,play significant roles in various animal physiological *** this study,we showed that *** serpins(Hlserpin-a and Hlserpin-b)were induced during blood-feeding in nymph ticks and exhibited anticoagulation activity in *** Hlserpins through RNA interference(RNAi)significantly impaired tick *** of mice with recombinant Hlserpins or passive transfer of Hlserpin antiserum significantly curtails the efficacy of tick ***,the transmission of the Langat virus(LGTV)from ticks to mice witnessed a substantial decrease when Hlserpins were *** findings suggest that inhibiting Hlserpins can hamper tick engorgement and pathogen transmission,indicating the potential of Hlserpins as a vaccine to countertick-borne diseases.

关键词： feeding LGTV serpin TBEV tick

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Immune functions of C-type lectins in medical arthropods

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Insect Science 2024年第3期31卷 652-662页

作者： Zhihao Ming Zhiqiang Chen Hao Tong Xia Zhou Tingting Feng Jianfeng Dai Institute of biology and Medical Sciences Jiangsu Key Laboratory of Infection and ImmunitySoochow UniversitySuzhouJiangsu ProvinceChina School of biology and Basic Medical Science Suzhou Medical College of Soochow UniversitySuzhouJiangsu ProvinceChina

C-type lectins(CTLs)are a family of proteins that contain 1 or more carbohydrate-recognition domains(CRDs)and bind to a broad repertoire of ligands in the presence of calcium *** play important roles in innate immune defenses against microorganisms by acting as pattern-recognition receptors(PRRs)for invading pathogens,such as bacteria,viruses,and *** binding to pathogen-associated ligands,CTLs mediate immune responses,such as agglutination,phagocytosis,and the activation of phenol oxidase progenitors,thereby clearing *** are an evolutionarily conserved family found in almost all vertebrates and *** arthropods can acquire and transmit a range pathogens through various approaches,such as bloodsucking,lancing,and parasitism,thus infecting humans and animals with related diseases,some of which can be *** studies have shown that lectins are important components of the arthropod immune system and are essential for the immune responses of arthropods to arthropod-borne *** article reviews the current understanding of the structure,function,and signaling pathways involved in CTLs derived from important medical arthropods.

关键词： arthropod C-type lectin innate immunity vector-borne disease

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Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions

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Virologica Sinica 2024年第1期39卷 123-133页

作者： Hongbo Guo Dan Liu Kuan Liu Yao Hou Chunyang Li Qiudi Li Xiaohui Ding Monique M.A.Verstegen Jikai Zhang Lingli Wang Yibo Ding Renxian Tang Xiucheng Pan Kuiyang Zheng Luc J.Wvan der Laan Qiuwei Pan Wenshi Wang Department of Pathogen biology and Immunology Jiangsu Key Laboratory of Immunity and MetabolismJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhou221004China Department of Gastroenterology and Hepatology Erasmus MC-University Medical CenterRotterdamNL-3015 CNthe Netherlands Department of Surgery Erasmus MC Transplant InstituteUniversity Medical CenterRotterdam3015CENL-3015 CNthe Netherlands Department of Infectious Diseases The Affiliated Hospital of Xuzhou Medical UniversityXuzhou221002China

Hepatitis E virus(HEV)infection can cause severe complications and high mortality,particularly in pregnant women,organ transplant recipients,individuals with pre-existing liver disease and immunosuppressed ***,there are still unmet needs for treating chronic HEV ***,we screened a best-in-class drug repurposing library consisting of 262 drugs/*** screening,we identified vidofludimus calcium and pyrazofurin as novel anti-HEV *** calcium is the next-generation dihydroorotate dehydrogenase(DHODH)inhibitor in the phase 3 pipeline to treat autoimmune diseases or SARS-CoV-2 *** selectively targets uridine monophosphate synthetase(UMPS).Their anti-HEV effects were further investigated in a range of cell culture models and human liver organoids models with wild type HEV strains and ribavirin treatment failure-associated HEV ***,both drugs exhibited a sizeable therapeutic window against *** instance,the IC50 value of vidofludimus calcium is 4.6–7.6-fold lower than the current therapeutic doses in ***,their anti-HEV mode of action depends on the blockage of pyrimidine ***,two drugs robustly inhibited ribavirin treatment failure-associated HEV mutants(Y1320H,G1634R).Their combination with IFN-αresulted in synergistic antiviral *** conclusion,we identified vidofludimus calcium and pyrazofurin as potent candidates for the treatment of HEV *** on their antiviral potency,and also the favorable safety profile identified in clinical studies,our study supports the initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E.

关键词： Hepatitis Evirus(HEV) Drug repurposing Vidofludimus calcium Pyrazofurin Pyrimidine biosynthesis

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Major royal-jelly proteins intake modulates immune functions and gut microbiota in mice

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Food Science and Human Wellness 2024年第1期13卷 444-453页

作者： Hang Wu Shican Zhou Wenjuan Ning Xiao Wu Xiaoxiao Xu Zejin Liu Wenhua Liu Kun Liu Lirong Shen Junpeng Wang Infection and immunity Institute and Translational Medical center of Huaihe Hospital Henan UniversityKaifeng 475000China College of biology Science and Engineering Hebei University of Economics and BusinessShijiazhuang 050061China College of Biosystems Engineering and Food Science Zhejiang Key Laboratory for Agro-Food ProcessingZhejiang UniversityHangzhou 310058China

In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in *** given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to *** splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand *** release of IL-4 was unaffected by ***,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory *** production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control *** of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of ***,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and *** results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.

关键词： Major royal-jelly proteins immunity Estrogen Gut microbiota Cytokines

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Plant grafting:Molecular mechanisms and applications

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Molecular Plant 2024年第1期17卷 75-91页

作者： Ming Feng Frauke Augstein Abdul Kareem Charles W.Melnyk Department of Plant biology Linnean Center for Plant BiologySwedish University of Agricultural SciencesAlmas allé575651 UppsalaSweden

People have grafted plants since antiquity for propagation,to increase yields,and to improve stress *** cutting and joining of tissues activates an incredible regenerative ability as different plants fuse and grow as *** over a hundred years,people have studied the scientific basis for how plants ***,new techniques and a deepening knowledge of the molecular basis for graft formation have allowed a range of previously ungraftable combinations to ***,we review recent developments in our understanding of graft formation,including the attachment and vascular formation *** analyze why plants graft and how biotic and abiotic factors influence successful *** also discuss the ability and inability of plants to graft,and how grafting has transformed both horticulture and fundamental plant *** our knowledge about plant grafting improves,new combinations and techniques will emerge to allow an expanded use of grafting for horticultural applications and to address fundamental research questions.

关键词： plant grafting regeneration mobile molecules tissue adhesion vascular differentiation stress tolerance

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Two hits are better than one:rational dual strategy efficiently fights neuroblastoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1802-1804页

作者： Jacques Zimmer Camille Rolin Markus Ollert Department of Infection and immunity Luxembourg Institute of HealthEsch-sur-AlzetteLuxembourg University of Luxembourg Esch-sur-AlzetteLuxembourg Department of Dermatology and Allergy center Odense Research Center for Anaphylaxis(ORCA)University of Southern DenmarkOdenseDenmark

The recently published landmark paper by Bergaggio et *** Roberto Chiarle’s group in Cancer Cell1 investigates an elegant double-hit strategy to improve anti-cancer *** important approach demonstrates in a preclinical model that chimeric antigen receptor(CAR)-T cell treatment can be rendered more efficient by increasing the cell surface expression of the CAR target structure via a small molecule.

关键词： neuroblastoma Cancer

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No evidence of predator odor avoidance in a North American bird community

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Avian Research 2024年第1期15卷 133-138页

作者： Austin Dotta Batur Yaman Alex Van Huynh Department of biology DeSales University2755 Station AvenueCenter ValleyPAUSA

Recent advances in our understanding of avian chemical communication have highlighted the importance of olfaction in many aspects of avian *** studies investigating predator avoidance behaviors in response to predator odor cues have produced mixed results across species and *** we assess if a community of birds in eastern Pennsylvania displays avoidance behaviors towards predator odor cues in a natural foraging *** use clay caterpillars to measure foraging activity by birds in the presence of predator(bobcat)urine,non-predator(rabbit)urine,and water controls in two different environmental contexts(field ***).Although we detected a weak trend for birds to forage less at predator urine-treated sites,we found no significant difference in avian foraging between the site *** did find that foraging rates between environmental contexts changed significantly over the course of the experiment,with forest sites showing decreasing foraging rates and field sites showing increasing foraging *** results reinforce the published literature that avoidance of predator odors by birds may not be ubiquitous across contexts and species.

关键词： Foraging Odor Olfaction Predation Predator-avoidance

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Simple and robust 3D MINFLUX excitation with a variable phase plate

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Light(Science & Applications) 2024年第7期13卷 1354-1363页

作者： Takahiro Deguchi Jonas Ries European Molecular biology Laboratory Cell Biology and BiophysicsHeidelbergGermany. Max Perutz Labs Vienna Biocenter Campus(VBC)ViennaAustria. University of Vienna Center for Molecular BiologyDepartment of Structural and Computational BiologyViennaAustria. University of Vienna Faculty of PhysicsViennaAustria

MINFLUX has achieved extraordinary resolution in superresolution imaging and single fluorophore *** is based on localizing single fluorophores by rapid probing with a patterned beam that features a local intensity *** implementations,however,are complex and expensive and are limited in speed and ***,we show that a combination of an electro-optical modulator with a segmented birefringent element such as a spatial light modulator produces a variable phase plate for which the phase can be scanned on the MHz *** or top-hat phase patterns generate high-contrast compact excitation point-spread functions for MINFLUX localization in the x,y,and z-direction,respectively,which can be scanned across a fluorophore within a microsecond,switched within 60 microseconds and alternated among different excitation *** discuss how to compensate for non-optimal performance of the components and present a robust 3D and multi-color MINFLUX excitation module,which we envision as an integral component of a high-performance and cost-effective open-source MINFLUX.

关键词： excitation phase switched

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Phase-driven progress in nanophotonic biosensing

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Light(Science & Applications) 2024年第5期13卷 798-800页

作者： Isabel Barth Hakho Lee center for Systems biology Massachusetts General HospitalHarvard Medical SchoolBostonMA 02114USA

In the continuous pursuit of enhancing the sensitivity of nanophotonic biosensors by leveraging phase phenomena,a recent development involved the engineering of an atomically thin Ge2Sb2Te5 layer on a silver nanofilm ... 详细信息

关键词： silver Ge2Sb2Te5 pursuit

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