Understanding the occurrence, development, and treatment of liver diseases is the main goal of hepatopathology research. Liver diseases are not only diverse but also highly heterogeneous among individuals. At present,...Understanding the occurrence, development, and treatment of liver diseases is the main goal of hepatopathology research. Liver diseases are not only diverse but also highly heterogeneous among individuals. At present, research on liver diseases is conducted mainly through cell culture, animal models, pathological specimens, etc. However, these methods cannot fully reveal the pathogenic mechanism and therapeutic characteristics of individualized liver diseases.Recent advances in three-dimensional cell culture technology(organoid culture techniques) include pluripotent stem cells and adult stem cells that are cultured in vitro to form self-organizing properties, making it possible to achieve individualized liver disease research. This review provides a comprehensive overview of the development of liver organoids, the existing and potential applications of liver regenerative medicine, the pathogenesis of liver disease heterogeneity, and drug screening.展开更多
BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the eff...BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.展开更多
Radio genetic therapy which combines gene therapy with radiotherapy has shown promising results in cancer treatment. In this study, an oncolytic adenovirusbased gene therapy system regulated by radiation was construct...Radio genetic therapy which combines gene therapy with radiotherapy has shown promising results in cancer treatment. In this study, an oncolytic adenovirusbased gene therapy system regulated by radiation was constructed to improve the cancer curative effect. This gene therapy system incorporated the radiation-inducible early growth response gene(Egr-1) promoter and the anticancer gene tumor necrosis factor-related apoptosis-inducing ligand(TRAIL). To confirm the antitumor effect of Ad-ET combined with^12C^(6+)tion irradiation, the survival and apoptosis fraction of tumor cells HT1080 and normal cells MRC-5 in combination treatment were detected by CCK-8 assay and FACS analysis. Then the expression levels of TRAIL gene and protein were tested by real-time PCR and western blotting. The results show that^12C^(6+)tion irradiation could induce cell growth inhibition and apoptosis by activating the TRAIL gene expression in tumor cells, while exhibiting no obvious toxicity to the normal lung cell line MRC-5. Theresults also demonstrate that use of an oncolytic adenovirusbased radiation-inducible gene therapy system together with^12C^(6+)tion irradiation could cause synergistic antitumor effect specifically in tumor cells but not in normal cells. The results indicate that the novel radio genetic therapy could potentiate radiation treatment by improving the safety and efficiency of monotherapy, and provide theoretical support for clinical application of combination treatment.展开更多
Objective To examine the expression of FLICE-inhibitory protein (FLIP) in juvenile idiopathic arthritis (JIA) and analyze its correlation with synovial inflammation. Methods The expression of FLIP was assessed in 11 J...Objective To examine the expression of FLICE-inhibitory protein (FLIP) in juvenile idiopathic arthritis (JIA) and analyze its correlation with synovial inflammation. Methods The expression of FLIP was assessed in 11 JIA and 3 normal synovial tissue samples by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The cell types expressing FLIP were further characterized,and the correlation of FLIP expression with the degree of synovial inflammation,as well as the activity of caspase 8 was then analyzed. Results RT-PCR revealed the expression of FLIP mRNA in all 11 JIA samples,but not in 3 normal synovial tissues. In JIA,FLIP expression could be found in both the lining and sublining layers,mainly in the macrophage-like cells. Moreover,the expression of FLIP in JIA synovial tissues was positively correlated with the degree of synovial inflammation (r=0.563,P<0.05). Conclusion The expression of antiapoptotic FLIP in JIA synovial tissue and its correlation to accumulation of inflammatory cells in synovial tissue suggests that FLIP potentially extends the lifespan of synovial cells and thus contributes to the progression of joint destruction.展开更多
Objective:To observe the effect of Xingnaojing injection on penumbra transformation in rats with acute cerebral ischemia.Methods:The rat model of middle cerebral artery occlusion(Middle cerebral artery occlusion,MCAO)...Objective:To observe the effect of Xingnaojing injection on penumbra transformation in rats with acute cerebral ischemia.Methods:The rat model of middle cerebral artery occlusion(Middle cerebral artery occlusion,MCAO)was established by suture occlusion.Except the sham operation group,the other groups were randomly divided into model group and Xingnaojing group.The rats in Xingnaojing group were intraperitoneally injected with Xingnaojing injectionaccording to 0.18ml/100g,and the sham operation group and model group were given the same amount of normal saline respectively.24 hours after the establishment of the model,the morphological changes of neurons in the penumbra of the rats were observed by Nissl staining,the ultrastructural changes of neurovascular unit(Neurovascular unit,NVU)were observed by transmission electron microscope(Transmission electron microscope,TEM),and the apoptosis of the ischemic penumbra was detected by in situ apoptosis(TdT-mediated Dutp Nick-End Labeling,TUNEL).Magnetic resonance imaging was used to observe the ischemic evolution of the penumbra of the same rat at 4.5 h and 24 h,respectively.Results:Compared with the sham operation group,the number of neurons in the model group was significantly reduced,the structure of Nissl corpuscles was destroyed,the outline was blurred or disappeared,the pathological morphology of NVU ultrastructure was obviously damaged under transmission electron microscope,a large number of apoptotic cells could be seen in the model group by TUNEL staining(P<0.01),and magnetic resonance imaging showed that there was a large area infarction in the brain tissue of the model group.Compared with the model group,the pathomorphology of neurons and NVU ultrastructure in Xingnaojing group was significantly improved,the number of apoptotic cells was significantly decreased(P<0.01),and the loss rate of penumbra was significantly lower in Xingnaojing group(P<0.05).Conclusion:Xingnaojing injection can improve the state of neurons in ischemic penumbra,reduce the injury of glial cells and microvessels,inhibit apoptosis,promote the transformation of penumbra in rats with acute cerebral ischemia,and save part of penumbra to some extent.it has a certain protective effect on the brain tissue of penumbra in the acute stage of cerebral ischemia.展开更多
An alkyl radical initiated cyclization/tandem reaction of alkyl bromides and alkyl electrophiles by using potassium metabisulphite(K_(2)S_(2)O_(5))as a connector is developed for the synthesis of various lactam-substi...An alkyl radical initiated cyclization/tandem reaction of alkyl bromides and alkyl electrophiles by using potassium metabisulphite(K_(2)S_(2)O_(5))as a connector is developed for the synthesis of various lactam-substituted alkyl sulfones.Notably,this process does not require a metal catalyst or metal powder reductant,highlighting its environmentally friendly features.The reaction demonstrates outstanding substrate adaptability and a high tolerance towards diverse functional groups.Furthermore,the biologically active molecules and commercially available drugs with a late-stage modification are also highly compatible with this transformation.Mechanistic studies revealed that the reaction proceeds through a single-step process involving intramolecular radical cyclization,"SO_(2)"insertion,and external alkyl incorporation.展开更多
Background:Despite the recent advances in treatments for rheumatoid arthritis (RA), there are still unmet needs in disease outcomes. This study aimed to analyze the satisfaction with drug therapies for RA according to...Background:Despite the recent advances in treatments for rheumatoid arthritis (RA), there are still unmet needs in disease outcomes. This study aimed to analyze the satisfaction with drug therapies for RA according to the levels of disease severity (patientassessed) and proportions of treatment cost to household income.Methods:This was a subgroup study of a cross-sectional study in patients with RA and their physicians. The patients were subdivided into different subgroups based on their self-assessed severity of RA and on the proportions of treatment cost to household income (<10%, 10-30%, 31-50%, and >50%). The Treatment Satisfaction Questionnaire for Medication version II was used to assess patients’ treatment satisfaction.Results:When considering all medications, effectiveness, convenience, and global satisfaction scores were lower in the severe and moderate RA subgroups than those in the mild and extremely mild RA subgroups (all P < 0.001). Effectiveness, side effects, and convenience scores were higher in the <10% subgroup compared to those in the >50% subgroup (all P < 0.05). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup ( F = 13.183, P = 0.004). For biological diseasemodifying anti-rheumatic drugs, effectiveness and convenience scores were lower in the severe RA subgroup than those in the extremely mild RA subgroup (both P < 0.05). Convenience score was higher in the <10% subgroup compared to that in the 31% to 50% and >50% subgroups ( F = 12.646, P = 0.005). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup ( F = 8.794, P = 0.032). Conclusion:Higher disease severity and higher financial burden were associated with lower patient satisfaction.展开更多
Background:Secukinumab demonstrated sustained efficacy in patients with ankylosing spondylitis(AS)through 5 years in pivotal Phase III studies.Here,we present efficacy and safety results(52-week)of secukinumab in pati...Background:Secukinumab demonstrated sustained efficacy in patients with ankylosing spondylitis(AS)through 5 years in pivotal Phase III studies.Here,we present efficacy and safety results(52-week)of secukinumab in patients with AS from the MEASURE 5 study.Methods:MEASURE 5 was a 52-week,Phase III,China-centric study.Eligible patients were randomly assigned(2:1)to receive subcutaneous secukinumab 150 mg or placebo weekly for the first five doses and then once every 4 weeks(q4w).All placebo patients switched to secukinumab 150 mg q4w starting at Week 16.Primary endpoint was Assessments of SpondyloArthritis international Society(ASAS)20 at Week 16.Randomization was stratified by region(China vs.non-China).Results:Of 458 patients(secukinumab 150 mg,N=305;placebo,N=153)randomized,327(71.4%)were from China and 131(28.6%)were not from China.Of these,97.7%and 97.4%patients completed Week 16 and 91.1%and 95.3%(placebo-secukinumab)patients completed Week 52 of treatment.The primary endpoint was met;secukinumab significantly improved ASAS20 response at Week 16 vs.placebo(58.4%vs.36.6%;P<0.0001);corresponding rate in the Chinese population was 56.0%vs.38.5%(P<0.01).All secondary efficacy endpoints significantly improved with secukinumab 150 mg in the overall population at Week 16;responses were maintained with a trend toward increased efficacy from Week 16 to 52.No new or unexpected safety signals were reported up to Week 52.Conclusions:Secukinumab 150 mg demonstrated rapid and significant improvement in signs and symptoms of AS.Secukinumab was well tolerated and the safety profile was consistent with previous reports.Efficacy and safety results were comparable between the overall and Chinese populations.展开更多
Bats are natural reservoir hosts for many viruses that produce no clinical symptoms in bats.Therefore, bats may have evolved effective mechanisms to control viral replication. However, little information is available ...Bats are natural reservoir hosts for many viruses that produce no clinical symptoms in bats.Therefore, bats may have evolved effective mechanisms to control viral replication. However, little information is available on bat immune responses to viral infection. Type I interferon(IFN) plays a key role in controlling viral infections. In this study, we report the cloning, expression, and biological activity of interferon β(IFNβ) from the Chinese microbat species, Myotis davidii. We demonstrated the upregulation of IFNB and IFN-stimulated genes in a kidney cell line derived from M. davidii after treatment with poly I:C or infection with Sendai virus. Furthermore, the recombinant IFNβ inhibited vesicular stomatitis virus and bat adenovirus replication in cell lines from two bat species, M. davidii and Rhinolophus sinicus. We provide the first in vitro evidence of IFNβ antiviral activity in microbats, which has important implications for virus interactions with these hosts.展开更多
Since the 2002–2003 severe acute respiratory syndrome(SARS) outbreak prompted a search for the natural reservoir of the SARS coronavirus, numerous alpha- and betacoronaviruses have been discovered in bats around the ...Since the 2002–2003 severe acute respiratory syndrome(SARS) outbreak prompted a search for the natural reservoir of the SARS coronavirus, numerous alpha- and betacoronaviruses have been discovered in bats around the world. Bats are likely the natural reservoir of alpha- and betacoronaviruses, and due to the rich diversity and global distribution of bats, the number of bat coronaviruses will likely increase. We conducted a surveillance of coronaviruses in bats in an abandoned mineshaft in Mojiang County, Yunnan Province, China, from 2012–2013. Six bat species were frequently detected in the cave: Rhinolophus sinicus, Rhinolophus affinis, Hipposideros pomona, Miniopterus schreibersii, Miniopterus fuliginosus, and Miniopterus fuscus. By sequencing PCR products of the coronavirus RNA-dependent RNA polymerase gene(Rd Rp), we found a high frequency of infection by a diverse group of coronaviruses in different bat species in the mineshaft. Sequenced partial Rd Rp fragments had 80%–99% nucleic acid sequence identity with well-characterized Alphacoronavirus species, including Bt CoV HKU2, Bt CoV HKU8, and Bt CoV1,and unassigned species Bt CoV HKU7 and Bt CoV HKU10. Additionally, the surveillance identified two unclassified betacoronaviruses, one new strain of SARS-like coronavirus, and one potentially new betacoronavirus species. Furthermore, coronavirus co-infection was detected in all six bat species, a phenomenon that fosters recombination and promotes the emergence of novel virus strains. Our findings highlight the importance of bats as natural reservoirs of coronaviruses and the potentially zoonotic source of viral pathogens.展开更多
This is the first country-wide surveillance of bat-borne viruses in Kenya spanning from 2012-2015 covering sites perceived to have medium to high level bat-human interaction. The objective of this surveillance study w...This is the first country-wide surveillance of bat-borne viruses in Kenya spanning from 2012-2015 covering sites perceived to have medium to high level bat-human interaction. The objective of this surveillance study was to apply a non-invasive approach using fresh feces to detect viruses circulating within the diverse species of Kenyan bats. We screened for both DNA and RNA viruses; specifically, astroviruses （AstVs）, adenoviruses （ADVs）, caliciviruses （CalVs）, coronaviruses （CoVs）, flaviviruses, filoviruses, paramyxoviruses （PMVs）, polyomaviruses （PYVs） and rotaviruses. We used family-specific primers, amplicon sequencing and further characterization by phyloge- netic analysis. Except for filoviruses, eight virus families were detected with varying distributions and positive rates across the five regions （former provinces） studied. AstVs （12.83%）, CoVs （3.97%）, PMV （2.4%）, ADV （2.26%）, PYV （1.65%）, CalVs （0.29%）, rotavirus （0.19%） and flavivirus （0.19%）. Novel CalVs were detected in Rousettus aegyptiacus and Mops condylurus while novel Rotavirus-A-related viruses were detected in Taphozous bats and R. aegyptiacus. The two Rotavirus A （RVA） strains detected were highly related to human strains with VP6 genotypes 12 and 116. Genotype 116 has previously been assigned to human RVA-strain B10 from Kenya only, which raises public health concern, particularly considering increased human-bat interaction. Additionally, 229E-like bat CoVs were detected in samples originating from Hipposideros bats roosting in sites with high human activity. Our findings confirm the presence of diverse viruses in Kenyan bats while providing extended knowledge on bat virus distribution. The detection of viruses highly related to human strains and hence of public health concern, underscores the importance of continuous surveillance.展开更多
MXenes, serving as a novel family of two-dimensional （2D） metal carbides, have attracted great research interest as one of the promising electrode materials due to the unique properties, However, to our best knowled...MXenes, serving as a novel family of two-dimensional （2D） metal carbides, have attracted great research interest as one of the promising electrode materials due to the unique properties, However, to our best knowledge, the 2D titanium carbide （one kind of MXene） used in constructing microsupercapacitors （MSCs） has not yet been reported to date, To this end, we firstly produce the MXene films on various kinds of substrates including polyethylene terephthalate （PET）, silicon oxide film and titanium plate through vacuum-filtrating and subsequent controlled transferring. On this basis, flexible all-solid-state symmetric MSCs on PET substrate based on MXene films are fabricated by micro-fabrication process using polyvinyl alcohol （PVA）JH2S04 as gel electrolyte. The results show that the as-made MSC has an ultrahigh rate performance with the scan rate of up to 1000V s-1 as well as an ultrafast frequency response （to = 0.5 ms）, In addition, the MSC delivers a large volumetric capacitance of 1,44 F cm 3, a high volumetric energy density （0.2 mWh cm-3） at the current density of 0.288 A cm 3 and a good cycling stability. Our research results presented here may pave the way for a new potential application of MXene in micro-power suppliers and micro-energy storage devices.展开更多
A silver quadrumer consisting of four parallel aligned rectangular nanobars, with three at the bottom and one at the top, is proposed to provide two Fano resonances. These two resonances can be adjusted either simulta...A silver quadrumer consisting of four parallel aligned rectangular nanobars, with three at the bottom and one at the top, is proposed to provide two Fano resonances. These two resonances can be adjusted either simultaneously or independently simply by tuning the geometrical parameters. Due to the formation of the two resonances in a relatively short wavelength range, one of them can be spectrally squeezed to be very narrow, which induces a very high figure of merit(FoM =45). By decomposing the scattering spectrum into bright modes and dark modes, the double Fano resonances are found to be originated from grouping the unit cells into two different groups. The evolution of the scattering spectrum with the central dimer position along the polarization direction suggests that the symmetry reducing induces the second Fano resonance and improves the Fo M of the first one. By introducing one more nanobar into the quadrumer system, the Fo M can approach the material's limit, although the dip is relatively shallow. The ultrahigh Fo M of the Fano resonance in the proposed quadrumer can provide ultra-sensitive refractive index sensing.Furthermore, the method for providing multiple independently tunable Fano resonances can offer new solutions to designing plasmonic-related nanolasers, photocatalysis, and biochemical sensors, etc.展开更多
Correction to： VIROLOGICA SINICA 2017, 32 （2）： 101-114 https：//doi.org/10.1007/sl 2250-016-3930-2The affiliation listed for Cecilia Waruhiu is incorrect. The byline and affiliation line should appear as shown be...Correction to： VIROLOGICA SINICA 2017, 32 （2）： 101-114 https：//doi.org/10.1007/sl 2250-016-3930-2The affiliation listed for Cecilia Waruhiu is incorrect. The byline and affiliation line should appear as shown below.展开更多
A new type of cooling stave with internal ribbed tube was proposed,and the heat transfer performance of the stave was studied by means of thermal test and numerical simulation.The temperature of cooling stave was moni...A new type of cooling stave with internal ribbed tube was proposed,and the heat transfer performance of the stave was studied by means of thermal test and numerical simulation.The temperature of cooling stave was monitored in the conditions of furnace gas temperature of 200-700 C and cooling water velocity of 0.2-1.0 m/s.The thermal test results show that the internal rib structure can form swirl in the water pipe and improve the cooling capacity of the cooling stave.The higher the furnace temperature or the lower the cooling water flow rate,the more obvious the advantage of the cooling stave with internal ribbed tube.The mathematical model of the cooling stave with internal ribbed tube was established by FLUENT software,and the influence of the internal rib structure parameters on the heat transfer performance of the cooling stave was discussed.It is suggested that the parameters of the internal ribbed tube should be 4 ribs,1 mm in height,5-7 mm in width,and 20-30 mm in lead.In the same common working conditions of the cooling stave,the maximum temperature of the newly designed cooling stave with internal ribbed tube is reduced by 5.6%compared with that of common cooling stave with round tube.The water flow rate in the internal ribbed tube only needs 0.9 m/s to reach the cooling effect of 2 m/s in the common tube cooling stave,which can save 55%of water.In case of water shortage accident of cooling stave,the maximum temperature of the cooling stave with internal ribbed tube is decreased by 22.4%compared with that of common round tube,which can effectively reduce the harm of water shortage and protect the cooling stave.展开更多
Porcine adenoviruses(PAdVs)are classified into three species,PAdV-A,PAdV-B,and PAdV-C.The genomes of PAdV-A and PAdV-C have been well characterized.However,the genome of PAdV-B has never been completely sequenced,and ...Porcine adenoviruses(PAdVs)are classified into three species,PAdV-A,PAdV-B,and PAdV-C.The genomes of PAdV-A and PAdV-C have been well characterized.However,the genome of PAdV-B has never been completely sequenced,and the epidemiology of PAdV-B remains unclear.In our study,we have identified a novel strain of PAdV-B,named PAdV-BHNU1,in porcine samples collected in China by viral metagenomic assay and general PCR.The genome of PAdV-BHNU1 is 31,743 bp in length and highly similar to that of California sea lion adenovirus 1(C.sea lion AdV-1),which contains typical mastadenoviral structures and some unique regions at the carboxy-terminal end.Especially,PAdV-BHNU1 harbors a dUTPase coding region not clustering with other mastadenoviruses except for C.sea lion AdV-1 and afiber coding region homologous with galectin 4 and 9 of animals.However,the variance of GC contents between PAdV-BHNU1(55%)and C.sea lion AdV-1(36%)indicates their differential evolutionary paths.Further epidemiologic study revealed a high positive rate(51.7%)of PAdV-B-HNU1 in porcine lymph samples,but low positive rates of 10.2%and16.1%in oral swabs and rectal swabs,respectively.In conclusion,this study characterized a novel representative genome of a lymphotropic PAdV-B with unique evolutionary origin,which contributes to the taxonomical and pathogenic studies of PAdVs.展开更多
A new method for the synthesis of 3-ethynyl-1-methylene-1,2-dihydronaphthalenes via copper-pro-moted palladium-catalyzed intermolecular alkynylative[5+1]carboannulation of 1-arylphenyl-prop-2-yn-1-yl acetates involvin...A new method for the synthesis of 3-ethynyl-1-methylene-1,2-dihydronaphthalenes via copper-pro-moted palladium-catalyzed intermolecular alkynylative[5+1]carboannulation of 1-arylphenyl-prop-2-yn-1-yl acetates involving C–H functionalization is described.Two terminal alkyne molecules serve as an alkynylation reagent and a one-carbon unit to enable alkynylative[5+1]carboannulation with excellent selectivity control,broad substrate scope and good tolerance of functional groups.展开更多
基金Supported by the Natural Science Foundation of Zhejiang Province,No.LY17H160047the Science Technology Department of Zhejiang Province,No.2018C37114the National Natural Science Foundation of China,No.81772628 and No.81703310
文摘Understanding the occurrence, development, and treatment of liver diseases is the main goal of hepatopathology research. Liver diseases are not only diverse but also highly heterogeneous among individuals. At present, research on liver diseases is conducted mainly through cell culture, animal models, pathological specimens, etc. However, these methods cannot fully reveal the pathogenic mechanism and therapeutic characteristics of individualized liver diseases.Recent advances in three-dimensional cell culture technology(organoid culture techniques) include pluripotent stem cells and adult stem cells that are cultured in vitro to form self-organizing properties, making it possible to achieve individualized liver disease research. This review provides a comprehensive overview of the development of liver organoids, the existing and potential applications of liver regenerative medicine, the pathogenesis of liver disease heterogeneity, and drug screening.
基金Supported by the Hospital Research Fund,No.SDFEYBS1805,No.SDFEYGJ2013 and No.XKTJ-HRC20210015Suzhou Science and Technology Development Project,No.SYS2020105,No.SKJY2021078 and No.2022SS43+2 种基金the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLZD2021002CNNC Elite Talent Program2022 State Key Laboratory of Radiological Medicine and Radiation Protection jointly built by Province and Ministry,No.GZK1202244.
文摘BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.
基金National Magnetic Confinement Fusion Science Program of China(No.2014GB112006)National Natural Science Foundation of China(No.11305204)Natural Science Foundation of Anhui Province of China(No.1508085SME220)
文摘Radio genetic therapy which combines gene therapy with radiotherapy has shown promising results in cancer treatment. In this study, an oncolytic adenovirusbased gene therapy system regulated by radiation was constructed to improve the cancer curative effect. This gene therapy system incorporated the radiation-inducible early growth response gene(Egr-1) promoter and the anticancer gene tumor necrosis factor-related apoptosis-inducing ligand(TRAIL). To confirm the antitumor effect of Ad-ET combined with^12C^(6+)tion irradiation, the survival and apoptosis fraction of tumor cells HT1080 and normal cells MRC-5 in combination treatment were detected by CCK-8 assay and FACS analysis. Then the expression levels of TRAIL gene and protein were tested by real-time PCR and western blotting. The results show that^12C^(6+)tion irradiation could induce cell growth inhibition and apoptosis by activating the TRAIL gene expression in tumor cells, while exhibiting no obvious toxicity to the normal lung cell line MRC-5. Theresults also demonstrate that use of an oncolytic adenovirusbased radiation-inducible gene therapy system together with^12C^(6+)tion irradiation could cause synergistic antitumor effect specifically in tumor cells but not in normal cells. The results indicate that the novel radio genetic therapy could potentiate radiation treatment by improving the safety and efficiency of monotherapy, and provide theoretical support for clinical application of combination treatment.
基金Supported by grants from the Chinese Ministry of Health (2008BAI59B01)the Department of Health of Sichuan province (020035)
文摘Objective To examine the expression of FLICE-inhibitory protein (FLIP) in juvenile idiopathic arthritis (JIA) and analyze its correlation with synovial inflammation. Methods The expression of FLIP was assessed in 11 JIA and 3 normal synovial tissue samples by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The cell types expressing FLIP were further characterized,and the correlation of FLIP expression with the degree of synovial inflammation,as well as the activity of caspase 8 was then analyzed. Results RT-PCR revealed the expression of FLIP mRNA in all 11 JIA samples,but not in 3 normal synovial tissues. In JIA,FLIP expression could be found in both the lining and sublining layers,mainly in the macrophage-like cells. Moreover,the expression of FLIP in JIA synovial tissues was positively correlated with the degree of synovial inflammation (r=0.563,P<0.05). Conclusion The expression of antiapoptotic FLIP in JIA synovial tissue and its correlation to accumulation of inflammatory cells in synovial tissue suggests that FLIP potentially extends the lifespan of synovial cells and thus contributes to the progression of joint destruction.
基金National Natural Science Foundation of China(No.81673899)。
文摘Objective:To observe the effect of Xingnaojing injection on penumbra transformation in rats with acute cerebral ischemia.Methods:The rat model of middle cerebral artery occlusion(Middle cerebral artery occlusion,MCAO)was established by suture occlusion.Except the sham operation group,the other groups were randomly divided into model group and Xingnaojing group.The rats in Xingnaojing group were intraperitoneally injected with Xingnaojing injectionaccording to 0.18ml/100g,and the sham operation group and model group were given the same amount of normal saline respectively.24 hours after the establishment of the model,the morphological changes of neurons in the penumbra of the rats were observed by Nissl staining,the ultrastructural changes of neurovascular unit(Neurovascular unit,NVU)were observed by transmission electron microscope(Transmission electron microscope,TEM),and the apoptosis of the ischemic penumbra was detected by in situ apoptosis(TdT-mediated Dutp Nick-End Labeling,TUNEL).Magnetic resonance imaging was used to observe the ischemic evolution of the penumbra of the same rat at 4.5 h and 24 h,respectively.Results:Compared with the sham operation group,the number of neurons in the model group was significantly reduced,the structure of Nissl corpuscles was destroyed,the outline was blurred or disappeared,the pathological morphology of NVU ultrastructure was obviously damaged under transmission electron microscope,a large number of apoptotic cells could be seen in the model group by TUNEL staining(P<0.01),and magnetic resonance imaging showed that there was a large area infarction in the brain tissue of the model group.Compared with the model group,the pathomorphology of neurons and NVU ultrastructure in Xingnaojing group was significantly improved,the number of apoptotic cells was significantly decreased(P<0.01),and the loss rate of penumbra was significantly lower in Xingnaojing group(P<0.05).Conclusion:Xingnaojing injection can improve the state of neurons in ischemic penumbra,reduce the injury of glial cells and microvessels,inhibit apoptosis,promote the transformation of penumbra in rats with acute cerebral ischemia,and save part of penumbra to some extent.it has a certain protective effect on the brain tissue of penumbra in the acute stage of cerebral ischemia.
基金the Scientific Research Fund of Hunan Provincial Education Department(21B0262 and 22B1094)the Natural Science Foundation of Hunan Province(2022JJ40857)the Hunan Provincial Innovation Foundation For Postgraduate(CX20230757)forfinancial support.
文摘An alkyl radical initiated cyclization/tandem reaction of alkyl bromides and alkyl electrophiles by using potassium metabisulphite(K_(2)S_(2)O_(5))as a connector is developed for the synthesis of various lactam-substituted alkyl sulfones.Notably,this process does not require a metal catalyst or metal powder reductant,highlighting its environmentally friendly features.The reaction demonstrates outstanding substrate adaptability and a high tolerance towards diverse functional groups.Furthermore,the biologically active molecules and commercially available drugs with a late-stage modification are also highly compatible with this transformation.Mechanistic studies revealed that the reaction proceeds through a single-step process involving intramolecular radical cyclization,"SO_(2)"insertion,and external alkyl incorporation.
基金This work was supported by grants from the Chinese National Key Research R&D Program(Nos.2017YFC0907601,2017YFC0907604)。
文摘Background:Despite the recent advances in treatments for rheumatoid arthritis (RA), there are still unmet needs in disease outcomes. This study aimed to analyze the satisfaction with drug therapies for RA according to the levels of disease severity (patientassessed) and proportions of treatment cost to household income.Methods:This was a subgroup study of a cross-sectional study in patients with RA and their physicians. The patients were subdivided into different subgroups based on their self-assessed severity of RA and on the proportions of treatment cost to household income (<10%, 10-30%, 31-50%, and >50%). The Treatment Satisfaction Questionnaire for Medication version II was used to assess patients’ treatment satisfaction.Results:When considering all medications, effectiveness, convenience, and global satisfaction scores were lower in the severe and moderate RA subgroups than those in the mild and extremely mild RA subgroups (all P < 0.001). Effectiveness, side effects, and convenience scores were higher in the <10% subgroup compared to those in the >50% subgroup (all P < 0.05). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup ( F = 13.183, P = 0.004). For biological diseasemodifying anti-rheumatic drugs, effectiveness and convenience scores were lower in the severe RA subgroup than those in the extremely mild RA subgroup (both P < 0.05). Convenience score was higher in the <10% subgroup compared to that in the 31% to 50% and >50% subgroups ( F = 12.646, P = 0.005). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup ( F = 8.794, P = 0.032). Conclusion:Higher disease severity and higher financial burden were associated with lower patient satisfaction.
基金This study was supported by Novartis Pharma AG,Basel,Switzerland and designed by Novartis personnelMedical writing support was funded by Novartis.
文摘Background:Secukinumab demonstrated sustained efficacy in patients with ankylosing spondylitis(AS)through 5 years in pivotal Phase III studies.Here,we present efficacy and safety results(52-week)of secukinumab in patients with AS from the MEASURE 5 study.Methods:MEASURE 5 was a 52-week,Phase III,China-centric study.Eligible patients were randomly assigned(2:1)to receive subcutaneous secukinumab 150 mg or placebo weekly for the first five doses and then once every 4 weeks(q4w).All placebo patients switched to secukinumab 150 mg q4w starting at Week 16.Primary endpoint was Assessments of SpondyloArthritis international Society(ASAS)20 at Week 16.Randomization was stratified by region(China vs.non-China).Results:Of 458 patients(secukinumab 150 mg,N=305;placebo,N=153)randomized,327(71.4%)were from China and 131(28.6%)were not from China.Of these,97.7%and 97.4%patients completed Week 16 and 91.1%and 95.3%(placebo-secukinumab)patients completed Week 52 of treatment.The primary endpoint was met;secukinumab significantly improved ASAS20 response at Week 16 vs.placebo(58.4%vs.36.6%;P<0.0001);corresponding rate in the Chinese population was 56.0%vs.38.5%(P<0.01).All secondary efficacy endpoints significantly improved with secukinumab 150 mg in the overall population at Week 16;responses were maintained with a trend toward increased efficacy from Week 16 to 52.No new or unexpected safety signals were reported up to Week 52.Conclusions:Secukinumab 150 mg demonstrated rapid and significant improvement in signs and symptoms of AS.Secukinumab was well tolerated and the safety profile was consistent with previous reports.Efficacy and safety results were comparable between the overall and Chinese populations.
基金funded by the National Natural Science Foundation of China (No. 31321001)
文摘Bats are natural reservoir hosts for many viruses that produce no clinical symptoms in bats.Therefore, bats may have evolved effective mechanisms to control viral replication. However, little information is available on bat immune responses to viral infection. Type I interferon(IFN) plays a key role in controlling viral infections. In this study, we report the cloning, expression, and biological activity of interferon β(IFNβ) from the Chinese microbat species, Myotis davidii. We demonstrated the upregulation of IFNB and IFN-stimulated genes in a kidney cell line derived from M. davidii after treatment with poly I:C or infection with Sendai virus. Furthermore, the recombinant IFNβ inhibited vesicular stomatitis virus and bat adenovirus replication in cell lines from two bat species, M. davidii and Rhinolophus sinicus. We provide the first in vitro evidence of IFNβ antiviral activity in microbats, which has important implications for virus interactions with these hosts.
基金funded by the National Natural Science Foundation of China(81290341)Scientific and Technological Basis Special Project(2013FY113500)+1 种基金China Mega-Project for Infectious Disease(2014ZX 10004001-003)from the Minister of Science and Technology of the People’s Republic of ChinaUSNIAID(R01AI110964)
文摘Since the 2002–2003 severe acute respiratory syndrome(SARS) outbreak prompted a search for the natural reservoir of the SARS coronavirus, numerous alpha- and betacoronaviruses have been discovered in bats around the world. Bats are likely the natural reservoir of alpha- and betacoronaviruses, and due to the rich diversity and global distribution of bats, the number of bat coronaviruses will likely increase. We conducted a surveillance of coronaviruses in bats in an abandoned mineshaft in Mojiang County, Yunnan Province, China, from 2012–2013. Six bat species were frequently detected in the cave: Rhinolophus sinicus, Rhinolophus affinis, Hipposideros pomona, Miniopterus schreibersii, Miniopterus fuliginosus, and Miniopterus fuscus. By sequencing PCR products of the coronavirus RNA-dependent RNA polymerase gene(Rd Rp), we found a high frequency of infection by a diverse group of coronaviruses in different bat species in the mineshaft. Sequenced partial Rd Rp fragments had 80%–99% nucleic acid sequence identity with well-characterized Alphacoronavirus species, including Bt CoV HKU2, Bt CoV HKU8, and Bt CoV1,and unassigned species Bt CoV HKU7 and Bt CoV HKU10. Additionally, the surveillance identified two unclassified betacoronaviruses, one new strain of SARS-like coronavirus, and one potentially new betacoronavirus species. Furthermore, coronavirus co-infection was detected in all six bat species, a phenomenon that fosters recombination and promotes the emergence of novel virus strains. Our findings highlight the importance of bats as natural reservoirs of coronaviruses and the potentially zoonotic source of viral pathogens.
基金funded by SinoAfrica Joint Research Center (SAJC201313 and SAJC 201605)
文摘This is the first country-wide surveillance of bat-borne viruses in Kenya spanning from 2012-2015 covering sites perceived to have medium to high level bat-human interaction. The objective of this surveillance study was to apply a non-invasive approach using fresh feces to detect viruses circulating within the diverse species of Kenyan bats. We screened for both DNA and RNA viruses; specifically, astroviruses （AstVs）, adenoviruses （ADVs）, caliciviruses （CalVs）, coronaviruses （CoVs）, flaviviruses, filoviruses, paramyxoviruses （PMVs）, polyomaviruses （PYVs） and rotaviruses. We used family-specific primers, amplicon sequencing and further characterization by phyloge- netic analysis. Except for filoviruses, eight virus families were detected with varying distributions and positive rates across the five regions （former provinces） studied. AstVs （12.83%）, CoVs （3.97%）, PMV （2.4%）, ADV （2.26%）, PYV （1.65%）, CalVs （0.29%）, rotavirus （0.19%） and flavivirus （0.19%）. Novel CalVs were detected in Rousettus aegyptiacus and Mops condylurus while novel Rotavirus-A-related viruses were detected in Taphozous bats and R. aegyptiacus. The two Rotavirus A （RVA） strains detected were highly related to human strains with VP6 genotypes 12 and 116. Genotype 116 has previously been assigned to human RVA-strain B10 from Kenya only, which raises public health concern, particularly considering increased human-bat interaction. Additionally, 229E-like bat CoVs were detected in samples originating from Hipposideros bats roosting in sites with high human activity. Our findings confirm the presence of diverse viruses in Kenyan bats while providing extended knowledge on bat virus distribution. The detection of viruses highly related to human strains and hence of public health concern, underscores the importance of continuous surveillance.
基金supported by the National Nature Science Foundations of China(Nos.21573265 and 51501208)
文摘MXenes, serving as a novel family of two-dimensional （2D） metal carbides, have attracted great research interest as one of the promising electrode materials due to the unique properties, However, to our best knowledge, the 2D titanium carbide （one kind of MXene） used in constructing microsupercapacitors （MSCs） has not yet been reported to date, To this end, we firstly produce the MXene films on various kinds of substrates including polyethylene terephthalate （PET）, silicon oxide film and titanium plate through vacuum-filtrating and subsequent controlled transferring. On this basis, flexible all-solid-state symmetric MSCs on PET substrate based on MXene films are fabricated by micro-fabrication process using polyvinyl alcohol （PVA）JH2S04 as gel electrolyte. The results show that the as-made MSC has an ultrahigh rate performance with the scan rate of up to 1000V s-1 as well as an ultrafast frequency response （to = 0.5 ms）, In addition, the MSC delivers a large volumetric capacitance of 1,44 F cm 3, a high volumetric energy density （0.2 mWh cm-3） at the current density of 0.288 A cm 3 and a good cycling stability. Our research results presented here may pave the way for a new potential application of MXene in micro-power suppliers and micro-energy storage devices.
基金National Natural Science Foundation of China(NSFC)(61675070,61378082,11704133)
文摘A silver quadrumer consisting of four parallel aligned rectangular nanobars, with three at the bottom and one at the top, is proposed to provide two Fano resonances. These two resonances can be adjusted either simultaneously or independently simply by tuning the geometrical parameters. Due to the formation of the two resonances in a relatively short wavelength range, one of them can be spectrally squeezed to be very narrow, which induces a very high figure of merit(FoM =45). By decomposing the scattering spectrum into bright modes and dark modes, the double Fano resonances are found to be originated from grouping the unit cells into two different groups. The evolution of the scattering spectrum with the central dimer position along the polarization direction suggests that the symmetry reducing induces the second Fano resonance and improves the Fo M of the first one. By introducing one more nanobar into the quadrumer system, the Fo M can approach the material's limit, although the dip is relatively shallow. The ultrahigh Fo M of the Fano resonance in the proposed quadrumer can provide ultra-sensitive refractive index sensing.Furthermore, the method for providing multiple independently tunable Fano resonances can offer new solutions to designing plasmonic-related nanolasers, photocatalysis, and biochemical sensors, etc.
文摘Correction to： VIROLOGICA SINICA 2017, 32 （2）： 101-114 https：//doi.org/10.1007/sl 2250-016-3930-2The affiliation listed for Cecilia Waruhiu is incorrect. The byline and affiliation line should appear as shown below.
基金funded by the National Natural Science Foundation of China(51574179)Nantong Science and Technology Project(JC2019154).
文摘A new type of cooling stave with internal ribbed tube was proposed,and the heat transfer performance of the stave was studied by means of thermal test and numerical simulation.The temperature of cooling stave was monitored in the conditions of furnace gas temperature of 200-700 C and cooling water velocity of 0.2-1.0 m/s.The thermal test results show that the internal rib structure can form swirl in the water pipe and improve the cooling capacity of the cooling stave.The higher the furnace temperature or the lower the cooling water flow rate,the more obvious the advantage of the cooling stave with internal ribbed tube.The mathematical model of the cooling stave with internal ribbed tube was established by FLUENT software,and the influence of the internal rib structure parameters on the heat transfer performance of the cooling stave was discussed.It is suggested that the parameters of the internal ribbed tube should be 4 ribs,1 mm in height,5-7 mm in width,and 20-30 mm in lead.In the same common working conditions of the cooling stave,the maximum temperature of the newly designed cooling stave with internal ribbed tube is reduced by 5.6%compared with that of common cooling stave with round tube.The water flow rate in the internal ribbed tube only needs 0.9 m/s to reach the cooling effect of 2 m/s in the common tube cooling stave,which can save 55%of water.In case of water shortage accident of cooling stave,the maximum temperature of the cooling stave with internal ribbed tube is decreased by 22.4%compared with that of common round tube,which can effectively reduce the harm of water shortage and protect the cooling stave.
基金funded by the National Key Research and Development Program of China(grant number 2017YFD0500104)the Hu-Xiang Youth Talents Scholar Program of Hunan Province(grant number 2017RS3017)+3 种基金the Science Fund for Distinguished Young Scholars of Hunan Province(grant number 2019JJ20004)National Natural Science Foundation of China(grant number 81902070)the Provincial Natural Science Foundation of Hunan Province(grant number 2019JJ50035)the Fundamental Research Funds for the Central Universities of China(grant number 531107051162)
文摘Porcine adenoviruses(PAdVs)are classified into three species,PAdV-A,PAdV-B,and PAdV-C.The genomes of PAdV-A and PAdV-C have been well characterized.However,the genome of PAdV-B has never been completely sequenced,and the epidemiology of PAdV-B remains unclear.In our study,we have identified a novel strain of PAdV-B,named PAdV-BHNU1,in porcine samples collected in China by viral metagenomic assay and general PCR.The genome of PAdV-BHNU1 is 31,743 bp in length and highly similar to that of California sea lion adenovirus 1(C.sea lion AdV-1),which contains typical mastadenoviral structures and some unique regions at the carboxy-terminal end.Especially,PAdV-BHNU1 harbors a dUTPase coding region not clustering with other mastadenoviruses except for C.sea lion AdV-1 and afiber coding region homologous with galectin 4 and 9 of animals.However,the variance of GC contents between PAdV-BHNU1(55%)and C.sea lion AdV-1(36%)indicates their differential evolutionary paths.Further epidemiologic study revealed a high positive rate(51.7%)of PAdV-B-HNU1 in porcine lymph samples,but low positive rates of 10.2%and16.1%in oral swabs and rectal swabs,respectively.In conclusion,this study characterized a novel representative genome of a lymphotropic PAdV-B with unique evolutionary origin,which contributes to the taxonomical and pathogenic studies of PAdVs.
基金We thank the National Natural Science Foundation of China(No.21625203 and 21871126)the Open Research Fund of School of Chemistry and Chemical Engineering,Henan Normal University(No.2021ZD01)for financial support.
文摘A new method for the synthesis of 3-ethynyl-1-methylene-1,2-dihydronaphthalenes via copper-pro-moted palladium-catalyzed intermolecular alkynylative[5+1]carboannulation of 1-arylphenyl-prop-2-yn-1-yl acetates involving C–H functionalization is described.Two terminal alkyne molecules serve as an alkynylation reagent and a one-carbon unit to enable alkynylative[5+1]carboannulation with excellent selectivity control,broad substrate scope and good tolerance of functional groups.
