Due to excellent thermal insulation performance at room temperature and ultralow density,silica aero-gels are candidates for thermal insulation.However,at high temperatures,the thermal insulation prop-erty of silica a...Due to excellent thermal insulation performance at room temperature and ultralow density,silica aero-gels are candidates for thermal insulation.However,at high temperatures,the thermal insulation prop-erty of silica aerogels decreased greatly caused by transparency to heat radiation.Opacifiers introduced into silica sol can block heat radiation yet destroy the uniformity of aerogels.Herein,we designed and prepared a silica aerogel composite with oriented and layered silica fibers(SFs),SiC nanowires(SiC_(NWs)),and silica aerogels,which were prepared by papermaking,chemical vapor infiltration(CVI),and sol-gel respectively.Firstly,oriented and layered SFs made still air a wall to block heat transfer by the solid phase.Secondly,SiC_(NWs) were grown in situ on the surface of SFs evenly to weave into the network,and the network reduced the gaseous thermal conductivity by dividing cracks in SFs/SiC_(NWs)/SA.Thirdly,SiC_(NWs) weakened the heat transfer by radiation at high temperatures.Therefore,SFs/SiC_(NWs)/SA presented remarkable thermal insulation(0.017 W(m K)^(-1) at 25℃,0.0287 W(m K)^(-1) at 500℃,and 0.094 W(m K)^(-1) at 1000℃).Besides,SFs/SiC_(NWs)/SA exhibited remarkable thermal stability(no size transform after being heat treated at 1000℃ for 1800 s)and tensile strength(0.75 MPa).These integrated properties made SFs/SiC_(NWs)/SA a promising candidate for highly efficient thermal insulators.展开更多
Male infertility constitutes a major global public health concern,with the underlying etiology remaining unidentified in nearly half of the diagnosed cases.Protein kinase CK1α(CK1α)functions as a pivotal regulator o...Male infertility constitutes a major global public health concern,with the underlying etiology remaining unidentified in nearly half of the diagnosed cases.Protein kinase CK1α(CK1α)functions as a pivotal regulator of cell cycle progression,pre-mRNA processing,and spliceosome-associated pathways through interactions with specific splicing factors.Comprehensive analyses revealed CK1αexpression in both germ cells and somatic cells of mouse testes,implicating its involvement in spermatogenic regulation.However,the physiological roles and mechanistic basis of CK1αfunction in Sertoli cells remain unclear.In this study,CK1αwas highly expressed in Sertoli cells,and conditional knockout of CK1αin murine Sertoli cells induced profound testicular atrophy and complete infertility.This phenotype was characterized by rapid depletion of Sertoli cells and spermatogenic dysfunction.Subsequent analyses demonstrated that CK1αregulated the fate determination of fetal and neonatal Sertoli cells in mice.At the molecular level,CK1αpromoted Sertoli cell survival through interaction with the splicing factor ZRSR1 to modulate apoptosis.Collectively,these findings establish CK1αas a key regulator of alternative splicing and male reproduction,providing critical insights into the molecular mechanisms underlying testicular development and reproductive function.展开更多
To address the poor mechanical properties of polydimethylsiloxane(PDMS)and enhance the understanding of the reinforcement mechanisms of aerogel network structures in rubber matrices,this study reinforced PDMS using an...To address the poor mechanical properties of polydimethylsiloxane(PDMS)and enhance the understanding of the reinforcement mechanisms of aerogel network structures in rubber matrices,this study reinforced PDMS using an ordered interconnected three-dimensional montmorillonite(MMT)aerogel network.The average pore diameter of the aerogels was successfully reduced from 11.53μm to 2.51μm by adjusting the ratio of poly(vinyl alcohol)(PVA)to MMT via directional freezing.Changes in the aerogel network were observed in field emission scanning electron microscope(FESEM)images.After vacuum impregnation,the aerogel network structure of the composites was observed using FESEM.Tensile tests indicated that as the pore diameter decreased,the elongation at break of the composites first increased to a peak of329.61%before decreasing,while the tensile strength and Young's modulus continuously increased to their maximum values of 6.29 MPa and24.67 MPa,respectively.Meanwhile,FESEM images of the tensile cracks and fracture surfaces showed that with a reduction in aerogel pore diameter,the degrees of crack deflection and interfacial debonding increased,presenting a rougher fracture surface.These phenomena enable the composites to dissipate substantial energy during tension,thus effectively improving the mechanical strength of the composites.The present work elucidates the bearing of ordered three-dimensional aerogel network structures on the performance of rubber matrices and provides crucial theoretical insights and technical guidance for the creation and optimization of high-performance PDMS-based composites.展开更多
Background Taurine performs multiple physiological functions,and the maintenance of taurine level for most mammals relies on active uptake from diet and endogenous taurine synthesis through its synthesis enzymes,inclu...Background Taurine performs multiple physiological functions,and the maintenance of taurine level for most mammals relies on active uptake from diet and endogenous taurine synthesis through its synthesis enzymes,including cysteine dioxygenase(CDO).In addition,uterus tissue and uterus fluid are rich in to urine,and to urine synthesis is regulated by estrogen(E2)and progesterone(P_(4)),the key hormones priming embryo-uterine crosstalk during embryo implantation,but the functional interactions and mechanisms among which are largely unknown.The present study was thus proposed to identify the effects of CDO and taurine on embryo implantation and related mechanisms by using Cdo knockout(KO)and ovariectomy(OVX)mouse models.Results The uterine CDO expression was assayed from the first day of plugging(d 1)to d 8 and the results showed that CDO expression level increased from d 1 to d 4,followed by a significant decline on d 5 and persisted to d 8,which was highly correlated with serum and uterine taurine levels,and serum P_(4) concentration.Next,Cdo KO mouse was established by CRISPER/Cas9.It was showed that Cdo deletion sharply decreased the taurine levels both in serum and uterus tissue,causing implantation defects and severe subfertility.However,the implantation defects in Cdo KO mice were partly rescued by the taurine supplementation.In addition,Cdo deletion led to a sharp decrease in the expressions of P_(4)receptor(PR)and its responsive genes Ihh,Hoxa10 and Hand2.Although the expression of uterine estrogen receptor(ERa)had no significant change,the levels of ERa induced genes(Muc1,Ltf)during the implantation window were upregulated after Cdo deletion.These accompanied by the suppression of stroma cell proliferation.Meanwhile,E2inhibited CDO expression through ERa and P_(4)upregulated CDO expression through PR.Conclusion The present study firstly demonstrates that taurine and CDO play prominent roles in uterine receptivity and embryo implantation by involving in E2-ERa and P_(4)-PR signaling.These are crucial for our understanding the mechanism of embryo implantation,and infer that taurine is a potential agent for improving reproductive efficiency of livestock industry and reproductive medicine.展开更多
Cellulose is the most abundant organic macromolecule in nature and is renewable,degradable,and biocompatible.The structure of native cellulose has not yet been completely elucidated.Part of cellulose is tightly combin...Cellulose is the most abundant organic macromolecule in nature and is renewable,degradable,and biocompatible.The structure of native cellulose has not yet been completely elucidated.Part of cellulose is tightly combined with lignin macromolecules through chemical bonds to form cellulose-lignin complexes(CLC).The existence of the CLC structure inhibits the complete separation of cellulose from lignocellulosic material,which not only increases the consumption of chemicals in the cooking process and causes environmental pollution,but also makes the cellulose subject to certain degradation during the deep delignification process.Therefore,elucidation of the relationship between the cellulose-lignin connection structure and performance is of great significance for efficient separation of cellulose.This article reviews the current research status of CLC and discusses the research progress regarding its biodegradation characteristics.展开更多
The purpose of this work was to grow SiC as binder to adhere diamond particles to graphite substrate by low pressure chemical vapor deposition （LPCVD） at 1100 ℃ and 100 Pa using methyltrichlorosilane （MTS： CH3Si...The purpose of this work was to grow SiC as binder to adhere diamond particles to graphite substrate by low pressure chemical vapor deposition （LPCVD） at 1100 ℃ and 100 Pa using methyltrichlorosilane （MTS： CH3SiCl3） as precursor. The composite coatings on graphite substrates were analyzed by various techniques. Results show that a dense SiC coating with a cloud-cluster shape was formed both on the diamond particles and the substrate after deposition, The thermal stress （290.6 MPa） strengthened the interfacial bonding between the diamond particle and the SiC coating, which is advantageous for the purpose of adhering diamond particles to graphite substrate. The applied load of sliding wear test was found to affect not only the friction coefficient, but also the wear surface morphology. With increasing loads, the asperity penetration was high and the friction coefficient decreased.展开更多
The reusable thermal protective system consisting of high emissivity coatings used on the surface and a low thermal conductivity substrate used inside must be created to protect the reused space vehicles,which could d...The reusable thermal protective system consisting of high emissivity coatings used on the surface and a low thermal conductivity substrate used inside must be created to protect the reused space vehicles,which could decrease the surface temperature by radiation and prevent heattransfer via展开更多
Most phages—viruses infecting prokaryotes—inject their genomes via a tail structure.The central tail tube,composed of tail tube protein(TTP),typically forms conserved hexameric or trimeric rings.In this paper,we rep...Most phages—viruses infecting prokaryotes—inject their genomes via a tail structure.The central tail tube,composed of tail tube protein(TTP),typically forms conserved hexameric or trimeric rings.In this paper,we report a novel pentameric TTP assembly,solved by cryo-electron microscopy(cryo-EM)at 3.5 A and 3.7 A resolution.Structural analysis reveals a highly negatively charged inner surface of this pentameric tube.Key residues in the loop connectingβ3 andβ4 strands are crucial for pentameric ring formation.Mismatches in interactions between stacked layers can induce curvature in the tube.The cryo-EM structure of the TTP polymer at the tube’s end shows thatβ-strands spanning amino acids 27-65 shift toward the central tunnel,potentially obstructing the passage of the phage genome.This study provides new structural insights into a unique TTP assembly,enhancing our understanding of phage assembly processes.展开更多
Introduction:The regulation of thyroid-stimulating hormone(TSH)synthesis involves neurotransmitters,with melatonin being a subject of ongoing debate.TSH transcription,synthesis,and secretion from the pituitary pars di...Introduction:The regulation of thyroid-stimulating hormone(TSH)synthesis involves neurotransmitters,with melatonin being a subject of ongoing debate.TSH transcription,synthesis,and secretion from the pituitary pars distalis(PD)is primarily regulated in a photoperiodic manner by thyrotropin-releasing hormone(TRH).In contrast,in the pituitary pars tuberalis(PT),mRNA transcription and alpha/beta chain synthesis,but not secretion,of a TSHlike product is regulated by melatonin.Conversely,non-photoperiodic melatonin might also affect the secretion of a TSH-like product from the PT.Nevertheless,the impact of exogenous melatonin on the underlying PD-TSH synthesis remains unclear.Casein kinase 1α(CK1α)plays a negative regulatory role in TSH synthesis in the mouse pituitary.Objective:We investigated whether non-photoperiodic melatonin affects PD-TSH synthesis through its interaction with CK1α.Methods:Immunohistochemistry and immunofluorescence staining detected the colocalization of the melatonin receptor MT1 with CK1αand TSH-βin the PD.RT-qPCR,western blotting,and ELISA revealed the effect of melatonin on Tshb mRNA,MTNR1A mRNA,Csnk1a1 mRNA,CK1αprotein,MT1 protein,and TSH levels.Results:Robust colocalization of the melatonin receptor MT1 with CK1αand TSH-βin the PD.Tshb mRNA and CK1αprotein expression levels peaked at opposite phases of the 24-h light:dark cycle.Exogenous melatonin administration promoted pituitary TSH synthesis,while concurrently inhibiting CK1αactivity.The upregulation of endogenous CK1αactivity in primary pituitary cells significantly blunted the melatonin stimulatory impact on Tshb mRNA and TSH levels.Mechanistically,the CK1αagonist pyrvinium abrogated melatonin-induced activation of p-PKC and p-CREB expression in vitro.Conclusion:The CK1α/PKC signaling pathway mediates the regulation of melatonin in pituitary TSH synthesis.We demonstrate an important theoretical and experimental basis for understanding the mechanism of endocrine system diseases caused by abnormal TSH synthesis in the pituitary.展开更多
Protonic ceramic electrolysis cells(PCECs)have attracted significant interest because of their efficiency and environmental sustainability in energy conversion.However,their commercial application is hindered by the a...Protonic ceramic electrolysis cells(PCECs)have attracted significant interest because of their efficiency and environmental sustainability in energy conversion.However,their commercial application is hindered by the absence of effective and robust electrodes capable of operating in harsh environments,such as those characterized by high vapor or CO_(2)concentrations.In this study,we developed a stable steam electrode composed of PrBaMn_(2)O_(5+δ)(PBM)and the durable proton conductor BaZr_(0.85)Y_(0.15)O_(3−δ)(BZY),which was enhanced with the deposition of PrOx nano-catalysts.The composite electrode exhibited a low polarization resistance(~0.34Ω·cm^(2)at 600℃),comparable to that of conventional cobalt-based electrodes.Additionally,extensive testing over hundreds of hours under severe conditions revealed exceptional durability,with no significant degradation observed.Notably,the electrode composited with cube-shaped BZY microcrystals and PBM showed a higher proton conductivity of 2.15×10^(−5)S·cm^(−1)at 500℃,representing an entire order of magnitude greater than that of the electrode composited with irregular nanosized BZY.In addition,the single cell achieved a superior electrolysis current of 2.0 A·cm^(−2)at 700℃and 1.3 V.These findings demonstrate the superiority of constructing an innovative interface between the mixed ionic‒electronic conductor(MIEC)and the proton conductor.Our work presents a promising strategy for designing durable steam electrodes for PCECs through a rational compositing approach.展开更多
There is a constant need for materials that combine hemostasis and osteogenesis in orthopedic surgery.Current hemostatic materials lack biodegradability,osteogenic properties,and hemostatic efficacy.In this study,we d...There is a constant need for materials that combine hemostasis and osteogenesis in orthopedic surgery.Current hemostatic materials lack biodegradability,osteogenic properties,and hemostatic efficacy.In this study,we developed a wax-like co-doped polyphosphate(CoPPW)by chelating sodium polyphosphate with cationic ions(Ca^(2+),Mg^(2+),and Sr^(2+)).Our results demonstrate that CoPPW was malleable and degraded optimally,releasing Mg^(2+)and Sr^(2+)ions initially and losing weight over 4 weeks.In vitro,CoPPW promoted better cell proliferation and osteogenic differentiation than beeswax,likely due to ion release.RT-PCR and transcriptome sequencing revealed that CoPPW significantly upregulated osteogenesis-related genes and bone-related protein expression.The activation of the PI3K/AKT signalling pathway confirmed osteogenesis,while the coagulation cascade pathway indicated effective hemostasis.In vivo,CoPPW was more effective in promoting bone regeneration and hemostasis compared to bone wax.Overall,CoPPW exhibits excellent hemostatic and osteogenic effects,making it a promising candidate for bone repair applications.展开更多
The COVID-19 pandemic has underscored the importance of in-depth research into the proteins encoded by coronaviruses(CoV),particularly the highly conserved nonstructural CoV proteins(nsp).Among these,the nsp13 helicas...The COVID-19 pandemic has underscored the importance of in-depth research into the proteins encoded by coronaviruses(CoV),particularly the highly conserved nonstructural CoV proteins(nsp).Among these,the nsp13 helicase of severe pathogenic MERS-CoV,SARS-CoV-2,and SARS-CoV is one of the most preserved CoV nsp.Utilizing single-molecule FRET,we discovered that MERS-CoV nsp13 unwinds DNA in distinct steps of about 9 bp when ATP is employed.If a different nucleotide is introduced,these steps diminish to 3−4 bp.Dwell-time analysis revealed 3−4 concealed steps within each unwinding process,which suggests the hydrolysis of 3−4 dTTP.Combining our observations with previous studies,we propose an unwinding model of CoV nsp13 helicase.This model suggests that the elongated and adaptable 1B-stalk of nsp13 may enable the 1B remnants to engage with the unwound single-stranded DNA,even as the helicase core domain has advanced over 3−4 bp,thereby inducing accumulated strain on the nsp13-DNA complex.Our findings provide a foundational framework for determining the unwinding mechanism of this unique helicase family.展开更多
A double network nested foam composite with tunable electromagnetic wave absorption performance was fabricated via a carbonization,impregnation,and chemical vapor infiltration method.The research results indicated tha...A double network nested foam composite with tunable electromagnetic wave absorption performance was fabricated via a carbonization,impregnation,and chemical vapor infiltration method.The research results indicated that the three-dimensional interconnected carbon foam was successfully enhanced by the SiC nanowire network.As expected,the electromagnetic absorption performance of the as-prepared SiC nanowire reinforced carbon foam(SiC_(nw)/CF)was greatly improved by the introduction of the SiC nanowires.The SiC_(nw)/CF composite prepared with a lower concentration of Ni catalyst possessed an excellent microwave absorption property with the lowest reflection loss value of-36.31 dB with a matched thickness of 2.60 mm accompanied by the widest effective bandwidth of 4.52 dB.An increase in catalyst concentration degraded the electromagnetic absorption ability to a certain extent.A potential microwave absorption schematic diagram was finally proposed,and it stated that the SiC nanowire network played an essential role in the improvement of the electromagnetic absorption properties.展开更多
Ceramic aerogels have promising applications in extreme environments,such as aerospace,but are severely limited by the sintering-prone nature of nanounits at high temperatures.However,they typically exhibit inadequate...Ceramic aerogels have promising applications in extreme environments,such as aerospace,but are severely limited by the sintering-prone nature of nanounits at high temperatures.However,they typically exhibit inadequate dimensional stability when exposed to high-temperature atmospheres,which can result in the deterioration of their macroscopic characteristics,eventually restricting their applications in extreme environments.Here,a(YYbErDyGd)_(2)SiO_(5)ceramic aerogel(ESA)was prepared at 1050℃by introducing high entropy into a ceramic aerogel,thereby enhancing its high-temperature thermal stability via the high-entropy effect.ESA was exposed to a temperature of 1600℃for 2 h without undergoing sintering.In addition,different fiber-reinforced ceramic aerogel composites are also explored,with a thermal conductivity of only 0.032 W/(m·K)at room temperature and 0.108 W/(m·K)at high temperature of 1000℃.These composites demonstrate no visible damage or deformation under extreme conditions across a substantial temperature range(−196 to 1300℃),a property that is paramount for applications in extreme environments.At 1100–1300℃,after 2 h of calcination,the composites exhibit a shrinkage rate of only 0.25%.After 600 s of butane torch ablation at 1300℃,the back temperature is only 110℃.Moreover,under 60%compression deformation,its maximum compression strength is 0.386 MPa.Even after 20 high-temperature thermal cycles(1300℃for 2 h),the sample maintains a low thermal conductivity of 0.043 W/(m·K)and a compressive strength of 0.259 MPa.This work provides a new perspective for exploring the limits of the strength and thermal properties of ceramic composites in the field of high-temperature insulation,particularly under extreme conditions.展开更多
Porous three-dimensional Si C/melamine-derived carbon foam(3 D-Si C/MDCF)composite with an original open pore structure was fabricated by the heat treatment of the commercial melamine foam(MF),carbonization of the sta...Porous three-dimensional Si C/melamine-derived carbon foam(3 D-Si C/MDCF)composite with an original open pore structure was fabricated by the heat treatment of the commercial melamine foam(MF),carbonization of the stable MF,and chemical vapor deposition of the ultra-thin Si C coating.Scanning electron microscopy(SEM)and X-ray diffraction(XRD)were employed to detect the microstructure and morphology of the as-prepared composites.The results indicated that the 3 D-Si C/MDCF composites with the coating structure were prepared successfully.The obtained minimum reflection loss was–29.50 d B when the frequency and absorption thickness were 11.36 GHz and 1.75 mm,respectively.Further,a novel strategy was put forward to state that the best microwave absorption property with a thin thickness of 1.65 mm was gained,where the minimum reflection loss was–24.51 d B and the frequency bandwidth was 3.08 GHz.The excellent electromagnetic wave absorption ability resulted from the specific cladding structure,which could change the raw dielectric property to acquire excellent impedance matching.This present work had a certain extend reference meaning for the potential applications of the lightweight wave absorption materials with target functionalities.展开更多
The pandemic of coronavirus disease 2019(COVID-19)is changing the world like never before.This crisis is unlikely contained in the absence of effective therapeutics or vaccine.The papain-like protease(PLpro)of severe ...The pandemic of coronavirus disease 2019(COVID-19)is changing the world like never before.This crisis is unlikely contained in the absence of effective therapeutics or vaccine.The papain-like protease(PLpro)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)plays essential roles in virus replication and immune evasion,presenting a charming drug target.Given the PLpro proteases of SARS-CoV-2 and SARS-CoV share significant homology,inhibitor developed for SARS-CoV PLpro is a promising starting point of therapeutic development.In this study,we sought to provide structural frameworks for PLpro inhibitor design.We determined the unliganded structure of SARS-CoV-2 PLpro mutant C111 S,which shares many structural features of SARS-CoV PLpro.This crystal form has unique packing,high solvent content and reasonable resolution 2.5 A°,hence provides a good possibility for fragment-based screening using crystallographic approach.We characterized the protease activity of PLpro in cleaving synthetic peptide harboring nsp2/nsp3 juncture.We demonstrate that a potent SARS-CoV PLpro inhibitor GRL0617 is highly effective in inhibiting protease activity of SARSCoV-2 with the IC50 of 2.2?0.3 mmol/L.We then determined the structure of SARS-CoV-2 PLpro complexed by GRL0617 to 2.6 A°,showing the inhibitor accommodates the S3 e S4 pockets of the substrate binding cleft.The binding of GRL0617 induces closure of the BL2 loop and narrows the substrate binding cleft,whereas the binding of a tetrapeptide substrate enlarges the cleft.Hence,our results suggest a mechanism of GRL0617 inhibition,that GRL0617 not only occupies the substrate pockets,but also seals the entrance to the substrate binding cleft hence prevents the binding of the LXGG motif of the substrate.展开更多
The pandemic of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a high number of deaths in the world.To combat it,it is necessary to develop a better understanding of how the virus infects ho...The pandemic of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a high number of deaths in the world.To combat it,it is necessary to develop a better understanding of how the virus infects host cells.Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate(HS)and sialic acid-containing glycolipids/glycoproteins.In this study,we examined and compared the binding of the subunits and spike(S)proteins of SARS-CoV-2,SARS-Co V,and Middle East respiratory disease(MERS)-Co V to these glycans.Our results revealed that the S proteins and subunits can bind to HS in a sulfation-dependent manner and no binding with sialic acid residues was detected.Overall,this work suggests that HS binding may be a general mechanism for the attachment of these coronaviruses to host cells,and supports the potential importance of HS in infection and in the development of antiviral agents against these viruses.展开更多
The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics.Drugging the multi-functional...The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics.Drugging the multi-functional papain-like protease(PLpro)domain of the viral nsp3 holds promise.However,none of the known coronavirus PLpro inhibitors has been shown to be in vivo active.Herein,we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity,including against the Sarbecoviruses(SARSCoV-1 and SARS-CoV-2),Merbecovirus(MERS-CoV),as well as the Alphacoronavirus(hCoV-229E and hCoVOC43).Importantly,F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice.F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage,as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity.Despite the significant difference of substrate recognition,mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue,whereas an allosteric inhibitor of MERSPLpro interacting with its 271E position.Our proof-ofconcept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anticoronavirus agents.The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.展开更多
Ultra-high-speed, ultra-large-capacity and ultra-long-haul （3U） are the forever pursuit of optical communication. As a new mode of optical communication, 3U transmission can greatly promote next generation optical i...Ultra-high-speed, ultra-large-capacity and ultra-long-haul （3U） are the forever pursuit of optical communication. As a new mode of optical communication, 3U transmission can greatly promote next generation optical internet and broadband mobile communication network development and technological progress, therefore it has become the focus of international high-tech intellectual property competition ground. This paper introduces the scientific problems, key technologies and important achievements in 3U transmission research.展开更多
基金supported by the National Natural Science Foun-dation of China(Grant No.U2167214).
文摘Due to excellent thermal insulation performance at room temperature and ultralow density,silica aero-gels are candidates for thermal insulation.However,at high temperatures,the thermal insulation prop-erty of silica aerogels decreased greatly caused by transparency to heat radiation.Opacifiers introduced into silica sol can block heat radiation yet destroy the uniformity of aerogels.Herein,we designed and prepared a silica aerogel composite with oriented and layered silica fibers(SFs),SiC nanowires(SiC_(NWs)),and silica aerogels,which were prepared by papermaking,chemical vapor infiltration(CVI),and sol-gel respectively.Firstly,oriented and layered SFs made still air a wall to block heat transfer by the solid phase.Secondly,SiC_(NWs) were grown in situ on the surface of SFs evenly to weave into the network,and the network reduced the gaseous thermal conductivity by dividing cracks in SFs/SiC_(NWs)/SA.Thirdly,SiC_(NWs) weakened the heat transfer by radiation at high temperatures.Therefore,SFs/SiC_(NWs)/SA presented remarkable thermal insulation(0.017 W(m K)^(-1) at 25℃,0.0287 W(m K)^(-1) at 500℃,and 0.094 W(m K)^(-1) at 1000℃).Besides,SFs/SiC_(NWs)/SA exhibited remarkable thermal stability(no size transform after being heat treated at 1000℃ for 1800 s)and tensile strength(0.75 MPa).These integrated properties made SFs/SiC_(NWs)/SA a promising candidate for highly efficient thermal insulators.
基金supported by the National Natural Science Foundation of China(32130098)。
文摘Male infertility constitutes a major global public health concern,with the underlying etiology remaining unidentified in nearly half of the diagnosed cases.Protein kinase CK1α(CK1α)functions as a pivotal regulator of cell cycle progression,pre-mRNA processing,and spliceosome-associated pathways through interactions with specific splicing factors.Comprehensive analyses revealed CK1αexpression in both germ cells and somatic cells of mouse testes,implicating its involvement in spermatogenic regulation.However,the physiological roles and mechanistic basis of CK1αfunction in Sertoli cells remain unclear.In this study,CK1αwas highly expressed in Sertoli cells,and conditional knockout of CK1αin murine Sertoli cells induced profound testicular atrophy and complete infertility.This phenotype was characterized by rapid depletion of Sertoli cells and spermatogenic dysfunction.Subsequent analyses demonstrated that CK1αregulated the fate determination of fetal and neonatal Sertoli cells in mice.At the molecular level,CK1αpromoted Sertoli cell survival through interaction with the splicing factor ZRSR1 to modulate apoptosis.Collectively,these findings establish CK1αas a key regulator of alternative splicing and male reproduction,providing critical insights into the molecular mechanisms underlying testicular development and reproductive function.
基金financially supported by the National Natural Science Foundation of China(Nos.21876164 and U2030203)A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘To address the poor mechanical properties of polydimethylsiloxane(PDMS)and enhance the understanding of the reinforcement mechanisms of aerogel network structures in rubber matrices,this study reinforced PDMS using an ordered interconnected three-dimensional montmorillonite(MMT)aerogel network.The average pore diameter of the aerogels was successfully reduced from 11.53μm to 2.51μm by adjusting the ratio of poly(vinyl alcohol)(PVA)to MMT via directional freezing.Changes in the aerogel network were observed in field emission scanning electron microscope(FESEM)images.After vacuum impregnation,the aerogel network structure of the composites was observed using FESEM.Tensile tests indicated that as the pore diameter decreased,the elongation at break of the composites first increased to a peak of329.61%before decreasing,while the tensile strength and Young's modulus continuously increased to their maximum values of 6.29 MPa and24.67 MPa,respectively.Meanwhile,FESEM images of the tensile cracks and fracture surfaces showed that with a reduction in aerogel pore diameter,the degrees of crack deflection and interfacial debonding increased,presenting a rougher fracture surface.These phenomena enable the composites to dissipate substantial energy during tension,thus effectively improving the mechanical strength of the composites.The present work elucidates the bearing of ordered three-dimensional aerogel network structures on the performance of rubber matrices and provides crucial theoretical insights and technical guidance for the creation and optimization of high-performance PDMS-based composites.
基金supported by the Natural Science Foundation of China (32130098)the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)。
文摘Background Taurine performs multiple physiological functions,and the maintenance of taurine level for most mammals relies on active uptake from diet and endogenous taurine synthesis through its synthesis enzymes,including cysteine dioxygenase(CDO).In addition,uterus tissue and uterus fluid are rich in to urine,and to urine synthesis is regulated by estrogen(E2)and progesterone(P_(4)),the key hormones priming embryo-uterine crosstalk during embryo implantation,but the functional interactions and mechanisms among which are largely unknown.The present study was thus proposed to identify the effects of CDO and taurine on embryo implantation and related mechanisms by using Cdo knockout(KO)and ovariectomy(OVX)mouse models.Results The uterine CDO expression was assayed from the first day of plugging(d 1)to d 8 and the results showed that CDO expression level increased from d 1 to d 4,followed by a significant decline on d 5 and persisted to d 8,which was highly correlated with serum and uterine taurine levels,and serum P_(4) concentration.Next,Cdo KO mouse was established by CRISPER/Cas9.It was showed that Cdo deletion sharply decreased the taurine levels both in serum and uterus tissue,causing implantation defects and severe subfertility.However,the implantation defects in Cdo KO mice were partly rescued by the taurine supplementation.In addition,Cdo deletion led to a sharp decrease in the expressions of P_(4)receptor(PR)and its responsive genes Ihh,Hoxa10 and Hand2.Although the expression of uterine estrogen receptor(ERa)had no significant change,the levels of ERa induced genes(Muc1,Ltf)during the implantation window were upregulated after Cdo deletion.These accompanied by the suppression of stroma cell proliferation.Meanwhile,E2inhibited CDO expression through ERa and P_(4)upregulated CDO expression through PR.Conclusion The present study firstly demonstrates that taurine and CDO play prominent roles in uterine receptivity and embryo implantation by involving in E2-ERa and P_(4)-PR signaling.These are crucial for our understanding the mechanism of embryo implantation,and infer that taurine is a potential agent for improving reproductive efficiency of livestock industry and reproductive medicine.
基金The authors are grateful for the support of the National Natural Science Foundation of China(No.21878070)Hubei Provincial Universities Outstanding Young and Middle-aged Technological Innovation Team Project(No.T201205).
文摘Cellulose is the most abundant organic macromolecule in nature and is renewable,degradable,and biocompatible.The structure of native cellulose has not yet been completely elucidated.Part of cellulose is tightly combined with lignin macromolecules through chemical bonds to form cellulose-lignin complexes(CLC).The existence of the CLC structure inhibits the complete separation of cellulose from lignocellulosic material,which not only increases the consumption of chemicals in the cooking process and causes environmental pollution,but also makes the cellulose subject to certain degradation during the deep delignification process.Therefore,elucidation of the relationship between the cellulose-lignin connection structure and performance is of great significance for efficient separation of cellulose.This article reviews the current research status of CLC and discusses the research progress regarding its biodegradation characteristics.
基金financially supported by the Major Achievements of Jiangsu Province(BA20130987)the Innovation Fund of Nanjing University of Aeronautics and Astronautics(No.KFJJ201440)
文摘The purpose of this work was to grow SiC as binder to adhere diamond particles to graphite substrate by low pressure chemical vapor deposition （LPCVD） at 1100 ℃ and 100 Pa using methyltrichlorosilane （MTS： CH3SiCl3） as precursor. The composite coatings on graphite substrates were analyzed by various techniques. Results show that a dense SiC coating with a cloud-cluster shape was formed both on the diamond particles and the substrate after deposition, The thermal stress （290.6 MPa） strengthened the interfacial bonding between the diamond particle and the SiC coating, which is advantageous for the purpose of adhering diamond particles to graphite substrate. The applied load of sliding wear test was found to affect not only the friction coefficient, but also the wear surface morphology. With increasing loads, the asperity penetration was high and the friction coefficient decreased.
文摘The reusable thermal protective system consisting of high emissivity coatings used on the surface and a low thermal conductivity substrate used inside must be created to protect the reused space vehicles,which could decrease the surface temperature by radiation and prevent heattransfer via
基金supported by the Chinese Academy of Sciences (Grant Nos. E4V4061 and E2VK311)supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (Grant No. 2021-I2M-1-037)supported by the National Natural Science Foundation of China (Grant Nos. 81971985 and 82272308).
文摘Most phages—viruses infecting prokaryotes—inject their genomes via a tail structure.The central tail tube,composed of tail tube protein(TTP),typically forms conserved hexameric or trimeric rings.In this paper,we report a novel pentameric TTP assembly,solved by cryo-electron microscopy(cryo-EM)at 3.5 A and 3.7 A resolution.Structural analysis reveals a highly negatively charged inner surface of this pentameric tube.Key residues in the loop connectingβ3 andβ4 strands are crucial for pentameric ring formation.Mismatches in interactions between stacked layers can induce curvature in the tube.The cryo-EM structure of the TTP polymer at the tube’s end shows thatβ-strands spanning amino acids 27-65 shift toward the central tunnel,potentially obstructing the passage of the phage genome.This study provides new structural insights into a unique TTP assembly,enhancing our understanding of phage assembly processes.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Introduction:The regulation of thyroid-stimulating hormone(TSH)synthesis involves neurotransmitters,with melatonin being a subject of ongoing debate.TSH transcription,synthesis,and secretion from the pituitary pars distalis(PD)is primarily regulated in a photoperiodic manner by thyrotropin-releasing hormone(TRH).In contrast,in the pituitary pars tuberalis(PT),mRNA transcription and alpha/beta chain synthesis,but not secretion,of a TSHlike product is regulated by melatonin.Conversely,non-photoperiodic melatonin might also affect the secretion of a TSH-like product from the PT.Nevertheless,the impact of exogenous melatonin on the underlying PD-TSH synthesis remains unclear.Casein kinase 1α(CK1α)plays a negative regulatory role in TSH synthesis in the mouse pituitary.Objective:We investigated whether non-photoperiodic melatonin affects PD-TSH synthesis through its interaction with CK1α.Methods:Immunohistochemistry and immunofluorescence staining detected the colocalization of the melatonin receptor MT1 with CK1αand TSH-βin the PD.RT-qPCR,western blotting,and ELISA revealed the effect of melatonin on Tshb mRNA,MTNR1A mRNA,Csnk1a1 mRNA,CK1αprotein,MT1 protein,and TSH levels.Results:Robust colocalization of the melatonin receptor MT1 with CK1αand TSH-βin the PD.Tshb mRNA and CK1αprotein expression levels peaked at opposite phases of the 24-h light:dark cycle.Exogenous melatonin administration promoted pituitary TSH synthesis,while concurrently inhibiting CK1αactivity.The upregulation of endogenous CK1αactivity in primary pituitary cells significantly blunted the melatonin stimulatory impact on Tshb mRNA and TSH levels.Mechanistically,the CK1αagonist pyrvinium abrogated melatonin-induced activation of p-PKC and p-CREB expression in vitro.Conclusion:The CK1α/PKC signaling pathway mediates the regulation of melatonin in pituitary TSH synthesis.We demonstrate an important theoretical and experimental basis for understanding the mechanism of endocrine system diseases caused by abnormal TSH synthesis in the pituitary.
基金supported by the National Natural Science Foundation of China(Nos.51502136 and 21978133)the Natural Science Foundation of Jiangsu Province(No.BK 20211260)the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,and the Top-notch Academic Programs Project of Jiangsu Higher Education Institutions(TAPP).
文摘Protonic ceramic electrolysis cells(PCECs)have attracted significant interest because of their efficiency and environmental sustainability in energy conversion.However,their commercial application is hindered by the absence of effective and robust electrodes capable of operating in harsh environments,such as those characterized by high vapor or CO_(2)concentrations.In this study,we developed a stable steam electrode composed of PrBaMn_(2)O_(5+δ)(PBM)and the durable proton conductor BaZr_(0.85)Y_(0.15)O_(3−δ)(BZY),which was enhanced with the deposition of PrOx nano-catalysts.The composite electrode exhibited a low polarization resistance(~0.34Ω·cm^(2)at 600℃),comparable to that of conventional cobalt-based electrodes.Additionally,extensive testing over hundreds of hours under severe conditions revealed exceptional durability,with no significant degradation observed.Notably,the electrode composited with cube-shaped BZY microcrystals and PBM showed a higher proton conductivity of 2.15×10^(−5)S·cm^(−1)at 500℃,representing an entire order of magnitude greater than that of the electrode composited with irregular nanosized BZY.In addition,the single cell achieved a superior electrolysis current of 2.0 A·cm^(−2)at 700℃and 1.3 V.These findings demonstrate the superiority of constructing an innovative interface between the mixed ionic‒electronic conductor(MIEC)and the proton conductor.Our work presents a promising strategy for designing durable steam electrodes for PCECs through a rational compositing approach.
基金supported by the National Natural Science Foundation Youth Fund,China(82102582)Natural Science Foundation of Beijing,China(7232119)+2 种基金European Union’s Horizon 2020 research and inno-vation program under the Marie Skłodowska-Curie(812765)Swedish Research Council(2020-04341)Carl TryggersFoundation(CTS 21:1704).
文摘There is a constant need for materials that combine hemostasis and osteogenesis in orthopedic surgery.Current hemostatic materials lack biodegradability,osteogenic properties,and hemostatic efficacy.In this study,we developed a wax-like co-doped polyphosphate(CoPPW)by chelating sodium polyphosphate with cationic ions(Ca^(2+),Mg^(2+),and Sr^(2+)).Our results demonstrate that CoPPW was malleable and degraded optimally,releasing Mg^(2+)and Sr^(2+)ions initially and losing weight over 4 weeks.In vitro,CoPPW promoted better cell proliferation and osteogenic differentiation than beeswax,likely due to ion release.RT-PCR and transcriptome sequencing revealed that CoPPW significantly upregulated osteogenesis-related genes and bone-related protein expression.The activation of the PI3K/AKT signalling pathway confirmed osteogenesis,while the coagulation cascade pathway indicated effective hemostasis.In vivo,CoPPW was more effective in promoting bone regeneration and hemostasis compared to bone wax.Overall,CoPPW exhibits excellent hemostatic and osteogenic effects,making it a promising candidate for bone repair applications.
基金supported by CRP-ICGEB Research Grant 2019(Grant number:CRP/CHN19-02)National Key Research and Development Program of China(Grant number:2016YFD0500300)supported by the Special Coronavirus(COVID-19)Research Pilot Grant Program from University of Cincinnati College of Medicine.
文摘The COVID-19 pandemic has underscored the importance of in-depth research into the proteins encoded by coronaviruses(CoV),particularly the highly conserved nonstructural CoV proteins(nsp).Among these,the nsp13 helicase of severe pathogenic MERS-CoV,SARS-CoV-2,and SARS-CoV is one of the most preserved CoV nsp.Utilizing single-molecule FRET,we discovered that MERS-CoV nsp13 unwinds DNA in distinct steps of about 9 bp when ATP is employed.If a different nucleotide is introduced,these steps diminish to 3−4 bp.Dwell-time analysis revealed 3−4 concealed steps within each unwinding process,which suggests the hydrolysis of 3−4 dTTP.Combining our observations with previous studies,we propose an unwinding model of CoV nsp13 helicase.This model suggests that the elongated and adaptable 1B-stalk of nsp13 may enable the 1B remnants to engage with the unwound single-stranded DNA,even as the helicase core domain has advanced over 3−4 bp,thereby inducing accumulated strain on the nsp13-DNA complex.Our findings provide a foundational framework for determining the unwinding mechanism of this unique helicase family.
基金supported by the National Natural Science Foundation of China[grant number 51772151,51761145103]the Nanjing University of Aeronautics and Astronautics PhD short-term visiting scholar project([2018]47)[grant number 190105DF06]the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘A double network nested foam composite with tunable electromagnetic wave absorption performance was fabricated via a carbonization,impregnation,and chemical vapor infiltration method.The research results indicated that the three-dimensional interconnected carbon foam was successfully enhanced by the SiC nanowire network.As expected,the electromagnetic absorption performance of the as-prepared SiC nanowire reinforced carbon foam(SiC_(nw)/CF)was greatly improved by the introduction of the SiC nanowires.The SiC_(nw)/CF composite prepared with a lower concentration of Ni catalyst possessed an excellent microwave absorption property with the lowest reflection loss value of-36.31 dB with a matched thickness of 2.60 mm accompanied by the widest effective bandwidth of 4.52 dB.An increase in catalyst concentration degraded the electromagnetic absorption ability to a certain extent.A potential microwave absorption schematic diagram was finally proposed,and it stated that the SiC nanowire network played an essential role in the improvement of the electromagnetic absorption properties.
基金supported by the National Natural Science Foundation of China(No.52272300)the Jiangsu Collaborative Innovation Center for Advanced Inorganic Function Composites,and the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Ceramic aerogels have promising applications in extreme environments,such as aerospace,but are severely limited by the sintering-prone nature of nanounits at high temperatures.However,they typically exhibit inadequate dimensional stability when exposed to high-temperature atmospheres,which can result in the deterioration of their macroscopic characteristics,eventually restricting their applications in extreme environments.Here,a(YYbErDyGd)_(2)SiO_(5)ceramic aerogel(ESA)was prepared at 1050℃by introducing high entropy into a ceramic aerogel,thereby enhancing its high-temperature thermal stability via the high-entropy effect.ESA was exposed to a temperature of 1600℃for 2 h without undergoing sintering.In addition,different fiber-reinforced ceramic aerogel composites are also explored,with a thermal conductivity of only 0.032 W/(m·K)at room temperature and 0.108 W/(m·K)at high temperature of 1000℃.These composites demonstrate no visible damage or deformation under extreme conditions across a substantial temperature range(−196 to 1300℃),a property that is paramount for applications in extreme environments.At 1100–1300℃,after 2 h of calcination,the composites exhibit a shrinkage rate of only 0.25%.After 600 s of butane torch ablation at 1300℃,the back temperature is only 110℃.Moreover,under 60%compression deformation,its maximum compression strength is 0.386 MPa.Even after 20 high-temperature thermal cycles(1300℃for 2 h),the sample maintains a low thermal conductivity of 0.043 W/(m·K)and a compressive strength of 0.259 MPa.This work provides a new perspective for exploring the limits of the strength and thermal properties of ceramic composites in the field of high-temperature insulation,particularly under extreme conditions.
基金supported by the National Natural Science Foundation of China(Grant Nos.51772151 and 51761145103)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Porous three-dimensional Si C/melamine-derived carbon foam(3 D-Si C/MDCF)composite with an original open pore structure was fabricated by the heat treatment of the commercial melamine foam(MF),carbonization of the stable MF,and chemical vapor deposition of the ultra-thin Si C coating.Scanning electron microscopy(SEM)and X-ray diffraction(XRD)were employed to detect the microstructure and morphology of the as-prepared composites.The results indicated that the 3 D-Si C/MDCF composites with the coating structure were prepared successfully.The obtained minimum reflection loss was–29.50 d B when the frequency and absorption thickness were 11.36 GHz and 1.75 mm,respectively.Further,a novel strategy was put forward to state that the best microwave absorption property with a thin thickness of 1.65 mm was gained,where the minimum reflection loss was–24.51 d B and the frequency bandwidth was 3.08 GHz.The excellent electromagnetic wave absorption ability resulted from the specific cladding structure,which could change the raw dielectric property to acquire excellent impedance matching.This present work had a certain extend reference meaning for the potential applications of the lightweight wave absorption materials with target functionalities.
基金supported by the National Key Research and Development Program of China(2016YFD0500300)National Science and Technology Major Project(2018ZX10101001,China)+3 种基金National Natural Science Foundation of China(Grant Nos.81572005,81772207,81971985,11775308 and 81802057)Beijing Municipal Natural Science Foundation(Grant Nos.7182117 and 7174288,China)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(Grant Nos.2017I2M-1-014 and 2016-I2M-1-013,China)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(Grant Nos.2018PT51009 and 2017PT31049,China)
文摘The pandemic of coronavirus disease 2019(COVID-19)is changing the world like never before.This crisis is unlikely contained in the absence of effective therapeutics or vaccine.The papain-like protease(PLpro)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)plays essential roles in virus replication and immune evasion,presenting a charming drug target.Given the PLpro proteases of SARS-CoV-2 and SARS-CoV share significant homology,inhibitor developed for SARS-CoV PLpro is a promising starting point of therapeutic development.In this study,we sought to provide structural frameworks for PLpro inhibitor design.We determined the unliganded structure of SARS-CoV-2 PLpro mutant C111 S,which shares many structural features of SARS-CoV PLpro.This crystal form has unique packing,high solvent content and reasonable resolution 2.5 A°,hence provides a good possibility for fragment-based screening using crystallographic approach.We characterized the protease activity of PLpro in cleaving synthetic peptide harboring nsp2/nsp3 juncture.We demonstrate that a potent SARS-CoV PLpro inhibitor GRL0617 is highly effective in inhibiting protease activity of SARSCoV-2 with the IC50 of 2.2?0.3 mmol/L.We then determined the structure of SARS-CoV-2 PLpro complexed by GRL0617 to 2.6 A°,showing the inhibitor accommodates the S3 e S4 pockets of the substrate binding cleft.The binding of GRL0617 induces closure of the BL2 loop and narrows the substrate binding cleft,whereas the binding of a tetrapeptide substrate enlarges the cleft.Hence,our results suggest a mechanism of GRL0617 inhibition,that GRL0617 not only occupies the substrate pockets,but also seals the entrance to the substrate binding cleft hence prevents the binding of the LXGG motif of the substrate.
基金supported by the National Natural Science Foundation of China(91853120)the National Major Scientific and Technological Special Project of China(2018ZX09711001-013 and 2018ZX09711001-005)+2 种基金the National Key Research and Development Program of China(2018YFE0111400 and 2016YFD0500300)the State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,the Chinese Academy of Medical Sciences and Peking Union Medical College,the NIH Research Project Grant Program(R01 EB025892)the CRP-ICGEB Research Grant 2019(CRP/CHN19-02)。
文摘The pandemic of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a high number of deaths in the world.To combat it,it is necessary to develop a better understanding of how the virus infects host cells.Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate(HS)and sialic acid-containing glycolipids/glycoproteins.In this study,we examined and compared the binding of the subunits and spike(S)proteins of SARS-CoV-2,SARS-Co V,and Middle East respiratory disease(MERS)-Co V to these glycans.Our results revealed that the S proteins and subunits can bind to HS in a sulfation-dependent manner and no binding with sialic acid residues was detected.Overall,this work suggests that HS binding may be a general mechanism for the attachment of these coronaviruses to host cells,and supports the potential importance of HS in infection and in the development of antiviral agents against these viruses.
基金partly supported by funding from Health@InnoHK,Innovation and Technology Commission,the Government of the Hong Kong Special Administrative RegionTheme-Based Research Scheme of the Research Grants Council(T11-709/21-N)+7 种基金the National Program on Key Research Project of China(2020YFA0707500 and 2020YFA0707504)Guangdong Natural Science Foundation(2022A1515010099)the University of Hong Kong Outstanding Young Researcher Awardthe University of Hong Kong Li Ka Shing Faculty of Medicine Research Output Prizethe High Level-Hospital Program,Health Commission of Guangdong Province,Chinathe research project of Hainan Academician Innovation Platform(YSPTZX202004)Emergency Key Program of Guangzhou Laboratory(EKPG22-01)the Swiss National Science Foundation,the National Research Programme Covid-19(No.4078P0_198290/1)。
文摘The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics.Drugging the multi-functional papain-like protease(PLpro)domain of the viral nsp3 holds promise.However,none of the known coronavirus PLpro inhibitors has been shown to be in vivo active.Herein,we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity,including against the Sarbecoviruses(SARSCoV-1 and SARS-CoV-2),Merbecovirus(MERS-CoV),as well as the Alphacoronavirus(hCoV-229E and hCoVOC43).Importantly,F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice.F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage,as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity.Despite the significant difference of substrate recognition,mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue,whereas an allosteric inhibitor of MERSPLpro interacting with its 271E position.Our proof-ofconcept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anticoronavirus agents.The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
文摘Ultra-high-speed, ultra-large-capacity and ultra-long-haul （3U） are the forever pursuit of optical communication. As a new mode of optical communication, 3U transmission can greatly promote next generation optical internet and broadband mobile communication network development and technological progress, therefore it has become the focus of international high-tech intellectual property competition ground. This paper introduces the scientific problems, key technologies and important achievements in 3U transmission research.
