Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)...Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.展开更多
Although there are challenges in treating traumatic central nervous system diseases,mesenchymal stem cell-de rived extracellular vesicles(MSC-EVs) have recently proven to be a promising non-cellular the rapy.We compre...Although there are challenges in treating traumatic central nervous system diseases,mesenchymal stem cell-de rived extracellular vesicles(MSC-EVs) have recently proven to be a promising non-cellular the rapy.We comprehensively evaluated the efficacy of mesenchymal stem cell-de rived extracellular vesicles in traumatic central nervous system diseases in this meta-analysis based on preclinical studies.Our meta-analysis was registered at PROSPERO(CRD42022327904,May 24,2022).To fully retrieve the most relevant articles,the following databases were thoro ughly searched:PubMed,Web of Science,The Cochrane Library,and Ovid-Embase(up to April 1,2022).The included studies were preclinical studies of mesenchymal stem cell-derived extracellular vesicles for traumatic central nervous system diseases.The Systematic Review Centre for Laboratory Animal Experimentation(SYRCLE)’s risk of bias tool was used to examine the risk of publication bias in animal studies.After screening 2347studies,60 studies were included in this study.A meta-analysis was conducted for spinal co rd injury(n=52) and traumatic brain injury(n=8).The results indicated that mesenchymal stem cell-derived extracellular vesicles treatment prominently promoted motor function recovery in spinal co rd injury animals,including rat Basso,Beattie and Bresnahan locomotor rating scale scores(standardized mean difference [SMD]:2.36,95% confidence interval [CI]:1.96-2.76,P <0.01,I2=71%) and mouse Basso Mouse Scale scores(SMD=2.31,95% CI:1.57-3.04,P=0.01,I2=60%) compared with controls.Further,mesenchymal stem cell-de rived extracellular vesicles treatment significantly promoted neurological recovery in traumatic brain injury animals,including the modified N eurological Severity Score(SMD=-4.48,95% CI:-6.12 to-2.84,P <0.01,I2=79%) and Foot Fault Test(SMD=-3.26,95% CI:-4.09 to-2.42,P=0.28,I2=21%) compared with controls.Subgroup analyses showed that characteristics may be related to the therapeutic effect of mesenchymal stem cell-de rived extra cellular vesicles.For Basso,Beattie and Bresnahan locomotor rating scale scores,the efficacy of allogeneic mesenchymal stem cell-derived extracellular vesicles was higher than that of xenogeneic mesenchymal stem cell-derived extracellular vesicles(allogeneic:SMD=2.54,95% CI:2.05-3.02,P=0.0116,I2=65.5%;xenogeneic:SMD:1.78,95%CI:1.1-2.45,P=0.0116,I2=74.6%).Mesenchymal stem cellde rived extracellular vesicles separated by ultrafiltration centrifugation combined with density gradient ultra centrifugation(SMD=3.58,95% CI:2.62-4.53,P <0.0001,I2=31%) may be more effective than other EV isolation methods.For mouse Basso Mouse Scale scores,placenta-derived mesenchymal stem cell-de rived extracellular vesicles worked better than bone mesenchymal stem cell-derived extracellular vesicles(placenta:SMD=5.25,95% CI:2.45-8.06,P=0.0421,I2=0%;bone marrow:SMD=1.82,95% CI:1.23-2.41,P=0.0421,I2=0%).For modified Neurological Severity Score,bone marrow-derived MSC-EVs worked better than adipose-derived MSC-EVs(bone marrow:SMD=-4.86,95% CI:-6.66 to-3.06,P=0.0306,I2=81%;adipose:SMD=-2.37,95% CI:-3.73 to-1.01,P=0.0306,I2=0%).Intravenous administration(SMD=-5.47,95% CI:-6.98 to-3.97,P=0.0002,I2=53.3%) and dose of administration equal to 100 μg(SMD=-5.47,95% CI:-6.98 to-3.97,P <0.0001,I2=53.3%)showed better res ults than other administration routes and doses.The heterogeneity of studies was small,and sensitivity analysis also indicated stable results.Last,the methodological quality of all trials was mostly satisfactory.In conclusion,in the treatment of traumatic central nervous system diseases,mesenchymal stem cell-derived extracellular vesicles may play a crucial role in promoting motor function recovery.展开更多
Owing to their high luminous efficiency and tunable emission in both red light and far-red light regions,Mn^(4+)ion-activated phosphors have appealed significant interest in photoelectric and energy conversion devices...Owing to their high luminous efficiency and tunable emission in both red light and far-red light regions,Mn^(4+)ion-activated phosphors have appealed significant interest in photoelectric and energy conversion devices such as white light emitting diode(W-LED),plant cultivation LED,and temperature thermometer.Up to now,Mn^(4+)has been widely introduced into the lattices of various inorganic hosts for brightly redemitting phosphors.However,how to correlate the structure-activity relationship between host framework,luminescence property,and photoelectric device is urgently demanded.In this review,we thoroughly summarize the recent advances of Mn^(4+)doped phosphors.Meanwhile,several strategies like co-doping and defect passivation for improving Mn^(4+)emission are also discussed.Most importantly,the relationship between the protocols for tailoring the structures of Mn^(4+)doped phosphors,increased luminescence performance,and the targeted devices with efficient photoelectric and energy conversion efficiency is deeply correlated.Finally,the challenges and perspectives of Mn^(4+)doped phosphors for practical applications are anticipated.We cordially anticipate that this review can deliver a deep comprehension of not only Mn^(4+)luminescence mechanism but also the crystal structure tailoring strategy of phosphors,so as to spur innovative thoughts in designing advanced phosphors and deepening the applications.展开更多
Gold(Au) nanostructures(NSs) have been widely employed as cocatalysts to improve the photoactivity of semiconductor materials, while a systematic summary of the engineering approaches of Au NSs to maximize the solar-t...Gold(Au) nanostructures(NSs) have been widely employed as cocatalysts to improve the photoactivity of semiconductor materials, while a systematic summary of the engineering approaches of Au NSs to maximize the solar-to-fuel conversion efficiency is still lacking. In this review, the recently developed strategies for elevating the overall photocatalytic performance of Au-based catalysts and the deep physical chemistry mechanisms are highlighted. Firstly, the synthetic approaches of Au NSs are summarized, followed by an elaboration on their multiple functions in improving photoactivity. Afterward, modification strategies of Au NSs used to enhance the photocatalytic efficiency of Au-semiconductor composites,including controlling the Au NSs morphology, size, crystal phase, defect engineering, alloying with different metals, modulating interfacial interaction, and introducing an external field, are summarized and discussed independently. Additionally, advanced characterization techniques that can provide insights into the charge dynamics of the photocatalysts are introduced. Finally, we share our opinion on the challenges and outline potentially promising opportunities and directions for efficient Au-based photocatalysis research moving forward. We sincerely look forward to this review can deliver insightful views to design efficient Au-based photocatalysts and spur certain innovations to other metal-based catalysts.展开更多
<strong>Objective</strong>: This paper aims to explore clinical status and related influence factors of pressure injury (PI) in the elderly inpatients with kidney disease, so as to provide reference for th...<strong>Objective</strong>: This paper aims to explore clinical status and related influence factors of pressure injury (PI) in the elderly inpatients with kidney disease, so as to provide reference for the prevention and treatment of PI in the elderly inpatients with kidney disease. <strong>Methods</strong>: Retrospective collection method is adopted to collect 158 clinical cases of the elderly inpatients with kidney disease aged ≥ 60 in the Nephrology Department, the First Affiliated Hospital of Jinan University from January 2017 to December 2019, and then least absolute shrinkage and selection Operator (LASSO) regression analysis is used to analyze 17 possible influence factors;finally Logistic regression model is established to analyze and screen influence factors of risk. <strong>Results</strong>: 1) Among 158 elderly inpatients with medium and high risk of PI, the incidence of PI is 20.25%;the most common stage of injury is stage I (42.5%);sacrococcygeal (60%) is the high-risk site of pressure injury. 2) LASSO regression analysis shows that history of present respiratory infection/respiratory failure (<em>β </em>= 1.2714. <em>P</em> < 0.05) and hospitalization time (<em>β</em> = 0.4177. <em>P </em>< 0.05) are independent factors influencing PI risk in the elderly inpatients with kidney disease. <strong>Concl</strong><strong>usio</strong><strong>n</strong>: The elderly patients with kidney disease and PI risk are the high incidence population of hospital acquired PI;for the elderly inpatients with kidney disease and having respiratory infection history or respiratory failure, prolonged hospitalization will significantly increase the risk of PI. Therefore, targeted preventive and control measures should be taken to reduce the incidence of PI.展开更多
Inducible nitric oxide synthase and N-methyI-D-aspartate receptors have been shown to participate in nerve cell injury during spinal cord ischemia. This study observed a protective effect of curcumin on ischemic spina...Inducible nitric oxide synthase and N-methyI-D-aspartate receptors have been shown to participate in nerve cell injury during spinal cord ischemia. This study observed a protective effect of curcumin on ischemic spinal cord injury. Models of spinal cord ischemia were established by ligating the lumbar artery from the left renal artery to the bifurcation of the abdominal aorta. At 24 hours after model establishment, the rats were intraperitoneally injected with curcumin, Reverse transcrip- tion-polymerase chain reaction and immunohistochemical results demonstrated that after spinal cord ischemia, inducible nitric oxide synthase and N-methyI-D-aspartate receptor mRNA and protein expression significantly increased. However, curcumin significantly decreased inducible nitric oxide synthase and N-methyI-D-aspartate receptor mRNA and protein expression in the ischemic spinal cord. Tadov scale results showed that curcumin significantly improved motor function of the rat hind limb after spinal cord ischemia. The results demonstrate that curcumin exerts a neuroprotective ef- fect against ischemic spinal cord injury by decreasing inducible nitric oxide synthase and N-methyI-D-aspartate receptor expression.展开更多
Based on results of chaos characteristics comparing one-dimensional iterative chaotic self-map x = sin（2/x） with infinite collapses within the finite region[-1, 1] to some representative iterative chaotic maps with ...Based on results of chaos characteristics comparing one-dimensional iterative chaotic self-map x = sin（2/x） with infinite collapses within the finite region[-1, 1] to some representative iterative chaotic maps with finite collapses （e.g., Logistic map, Tent map, and Chebyshev map）, a new adaptive mutative scale chaos optimization algorithm （AMSCOA） is proposed by using the chaos model x = sin（2/x）. In the optimization algorithm, in order to ensure its advantage of speed convergence and high precision in the seeking optimization process, some measures are taken： 1） the searching space of optimized variables is reduced continuously due to adaptive mutative scale method and the searching precision is enhanced accordingly; 2） the most circle time is regarded as its control guideline. The calculation examples about three testing functions reveal that the adaptive mutative scale chaos optimization algorithm has both high searching speed and precision.展开更多
Graphitic carbon nitride(g-C_(3)N_(4))has attracted great interest in photocatalysis and photoelectrocatalysis.However,their poor hydrophilicity poses a great challenge for their applications in aqueous environment.He...Graphitic carbon nitride(g-C_(3)N_(4))has attracted great interest in photocatalysis and photoelectrocatalysis.However,their poor hydrophilicity poses a great challenge for their applications in aqueous environment.Here,we demonstrate synthesis of a hydrophilic bi-functional hierarchical architecture by the assembly of B-doped g-C_(3)N_(4)nanoplatelets.Such hierarchical B-doped g-C_(3)N_(4)material enables full utilization of their highly enhanced visible light absorption and photogenerated carrier separation in aqueous medium,leading to an excellent photocatalytic H_(2)O_(2)production rate of 4240.3μM g^(-1)h^(-1),2.84,2.64 and 2.13 times higher than that of the bulk g-C_(3)N_(4),g-C_(3)N_(4)nanoplatelets and bulk B doped g-C_(3)N_(4),respectively.Photoanodes based on these hierarchical architectures can generate an unprecedented photocurrent density of 1.72 m A cm^(-2)at 1.23 V under AM 1.5 G illumination for photoelectrochemical water splitting.This work makes a fundamental improvement towards large-scale exploitation of highly active,hydrophilic and stable metal-free g-C_(3)N_(4)photocatalysts for various practical applications.展开更多
Studies have shown that estrogen has neuroprotective effects on the nigrostriatal system. The present study established a Parkinson＇s disease model in C57BL/6 mice by intraperitoneal injection of 1-methyl-4-phenyl-1,...Studies have shown that estrogen has neuroprotective effects on the nigrostriatal system. The present study established a Parkinson＇s disease model in C57BL/6 mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrapyridine. The mice were subjected to 1713 estradiol injection into the lateral ventricle. Immunofluorescence double staining showed that estrogen increased tyrosine hydroxylase and calbindin-D28K expression and co-expression in dopaminergic neurons of midbrain substantia nigra pars compacta of model mice. Behavior experiments showed that estrogen improved swimming and hanging behaviors in this mouse model of Parkinson＇s disease.展开更多
In this paper, we consider the following coupled Schrodinger system with χ^(2) nonlinearities {-Δu1+V1(x)u1=αu1u2,x∈R^N,-Δu2+V2(x)u2=α/2u^21+βu^22,x∈R^N.which arises from second-harmonic generation in quadrati...In this paper, we consider the following coupled Schrodinger system with χ^(2) nonlinearities {-Δu1+V1(x)u1=αu1u2,x∈R^N,-Δu2+V2(x)u2=α/2u^21+βu^22,x∈R^N.which arises from second-harmonic generation in quadratic media. Here V1(x) and V2(x) are radially positive functions, 2 ≤ N < 6, α > 0 and α > β. Assume that the potential functions V1(x) and V2(x) satisfy some algebraic decay at infinity. Applying the finite dimensional reduction method, we construct an unbounded sequence of non-radial vector solutions of synchronized type.展开更多
Fruit curving lowers the commercial value of cucumber and leads to significant economic losses.The mechanism driving the abnormal curving of cucumber is largely unknown.Through our previous work,we discovered that 2 d...Fruit curving lowers the commercial value of cucumber and leads to significant economic losses.The mechanism driving the abnormal curving of cucumber is largely unknown.Through our previous work,we discovered that 2 days post-anthesis(DPA)was the key time point at which various phenotypic and genotypic characteristics of cucumber fruits are determined.Here,we analyzed the transcriptome of the concave(C1)and convex(C2)sides of curved fruits at 2 DPA by Gene Ontology(GO)enrichment and functional pathway enrichment analyses and identified auxin as a putative factor influencing fruit curvature.Changes in the curve angle in the fruits and exogenous auxin treatment analyses showed that asymmetric auxin distribution induces fruit curving.Identification of differentially expressed genes(DEGs)related to auxin and qPCR validation showed that CsYUC10b had the most significant differential expression when both sides of the curved fruits were compared.Gene functional analysis showed that the transcript levels of CsYUC10b and the auxin concentration were even on both sides of the fruit in CsYUC10b-overexpressing plants,which in turn contributed to an equal rate of growth of both sides of cucumber fruits and resulted in a straight shape of the fruits.Thus,we conclude that CsYUC10b promotes the formation of straight cucumber fruits,with possible applications in the production and breeding of cucumber.展开更多
Ischemic stroke induces a series of complex pathophysiological events including blood-brain barrier disruption, inflammatory response and neuronal apoptosis. Previous studies demonstrate that ischemic preconditioning ...Ischemic stroke induces a series of complex pathophysiological events including blood-brain barrier disruption, inflammatory response and neuronal apoptosis. Previous studies demonstrate that ischemic preconditioning attenuates ischemic brain damage via inhibiting blood-brain barrier disruption and the inflammatory response. Rats underwent transient （15 minutes） occlusion of the bilateral common carotid artery with 48 hours of reperfusion, and were subjected to permanent middle cerebral artey occlusion. This study explored whether ischemic preconditioning could reduce ischemic brain injury and relevant molecular mechanisms by inhibiting neuronal apoptosis. Results found that at 72 hours following cerebral ischemia, myeloperoxidase activity was enhanced, malondialdehyde levels increased, and neurological function was obviously damaged. Simultaneously, neuronal apoptosis increased, and nuclear factor-KB and cleaved caspase-3 expression was significantly increased in ischemic brain tissues. Ischemic preconditioning reduced the cerebral ischemia-induced inflammatory response, lipid peroxidation, and neurological function injury. In addition, ischemic preconditioning decreased nuclear factor-KB p65 and cleaved caspase-3 expression. These results suggested that ischemic preconditioning plays a protective effect against ischemic brain injury by suppressing the inflammatory response, reducing lipid peroxidation, and neuronal apoptosis via inhibition of nuclear factor-KB and cleaved caspase-3 expression.展开更多
Here we propose a hybrid polymer-LN waveguide for achieving phase-matched second-harmonic generation(SHG).From the aspect of super-mode theory,the geometric parameters of the hybrid semi-nonlinear waveguide were optim...Here we propose a hybrid polymer-LN waveguide for achieving phase-matched second-harmonic generation(SHG).From the aspect of super-mode theory,the geometric parameters of the hybrid semi-nonlinear waveguide were optimized to utilize both symmetric(even)and antisymmetric(odd)modes of the pump and SHG waves so as to facilitate phase matching with large modal overlap.Phase matching between a fundamental even(TE_(00)-like)mode at 1320 nm and a fundamental odd(TE_(01)-like)mode at 660 nm was found with a calculated modal overlap integral of 0.299,while utilizing the largest nonlinear coefficient d_(33),and achieving an efficient calculated normalized conversion efficiency of 148%W^(-1)·cm^(-2).Considering the fabrication feasibility of such hybrid waveguide with features including etchless,large dimension,and low structural sensitivity,we believe our findings would provide a useful reference for future on-chip efficient nonlinear conversion devices.展开更多
Purpose: To explore the fever-related risk factors of inpatients in Rehabilitation Department, and to provide reference for patients with high risk of fever to take corresponding nursing measures. Methods: The study w...Purpose: To explore the fever-related risk factors of inpatients in Rehabilitation Department, and to provide reference for patients with high risk of fever to take corresponding nursing measures. Methods: The study was conducted on the Rehabilitation Department of The First Affiliated Hospital of Jinan University from July 2019 to December 2019. The fever group included 51 patients and the non-fever group included 49 patients without fever. The two groups of clinical data, comorbidities, related laboratory values, possible risk factors of fever were analyzed by case regression analysis, and the relevant risk factors were screened out by LASSO (least absolute shrinkage and selection operator) regression analysis. Results: According to the results of Lasso regression analysis, pressure sore or skin infection, history of hypertension, current history of respiratory tract infection, feeding patterns were the higher risk factors of fever in inpatients in Rehabilitation Department, while the first course of disease, main diagnosis, history of respiratory tract infection within half a year, kidney damage and hospitalization days were lower risk factors. Conclusion: This study is helpful to early identify the fever risk of inpatients in Rehabilitation Department, and provide reference basis for high-risk fever patients to take positive and effective nursing measures.展开更多
The escalating prevalence of anterior cruciate ligament(ACL)injuries in sports necessitates innovative strategies for ACL reconstruction.In this study,we propose a multiphasic bone-ligament-bone(BLB)integrated scaffol...The escalating prevalence of anterior cruciate ligament(ACL)injuries in sports necessitates innovative strategies for ACL reconstruction.In this study,we propose a multiphasic bone-ligament-bone(BLB)integrated scaffold as a potential solution.The BLB scaffold comprised two polylactic acid(PLA)/deferoxamine(DFO)@mesoporous hydroxyapatite(MHA)thermally induced phase separation(TIPS)scaffolds bridged by silk fibroin(SF)/connective tissue growth factor(CTGF)@Poly(L-lactide-co-ε-caprolactone)(PLCL)nanofiber yarn braided scaffold.This combination mimics the native architecture of the ACL tissue.The mechanical properties of the BLB scaffolds were determined to be compatible with the human ACL.In vitro experiments demonstrated that CTGF induced the expression of ligament-related genes,while TIPS scaffolds loaded with MHA and DFO enhanced the osteogenic-related gene expression of bone marrow stem cells(BMSCs)and promoted the migration and tubular formation of human umbilical vein endothelial cells(HUVECs).In rabbit models,the BLB scaffold efficiently facilitated ligamentization and graft-bone integration processes by providing bioactive substances.The double delivery of DFO and calcium ions by the BLB scaffold synergistically promoted bone regeneration,while CTGF improved collagen formation and ligament healing.Collectively,the findings indicate that the BLB scaffold exhibits substantial promise for ACL reconstruction.Additional investigation and advancement of this scaffold may yield enhanced results in the management of ACL injuries.展开更多
In 2022,a global outbreak of Mpox(formerly monkeypox)occurred in various countries across Europe and America and rapidly spread to more than 100 countries and regions.The World Health Organization declared the outbrea...In 2022,a global outbreak of Mpox(formerly monkeypox)occurred in various countries across Europe and America and rapidly spread to more than 100 countries and regions.The World Health Organization declared the outbreak to be a public health emergency of international concern due to the rapid spread of the Mpox virus.Consequently,nations intensified their efforts to explore treatment strategies aimed at combating the infection and its dissemination.Nevertheless,the available therapeutic options for Mpox virus infection remain limited.So far,only a few numbers of antiviral compounds have been approved by regulatory authorities.Given the high mutability of the Mpox virus,certain mutant strains have shown resistance to existing pharmaceutical interventions.This highlights the urgent need to develop novel antiviral drugs that can combat both drug resistance and the potential threat of bioterrorism.Currently,there is a lack of comprehensive literature on the pathophysiology and treatment of Mpox.To address this issue,we conducted a review covering the physiological and pathological processes of Mpox infection,summarizing the latest progress of anti-Mpox drugs.Our analysis encompasses approved drugs currently employed in clinical settings,as well as newly identified small-molecule compounds and antibody drugs displaying potential antiviral efficacy against Mpox.Furthermore,we have gained valuable insights from the process of Mpox drug development,including strategies for repurposing drugs,the discovery of drug targets driven by artificial intelligence,and preclinical drug development.The purpose of this review is to provide readers with a comprehensive overview of the current knowledge on Mpox.展开更多
The established and ongoing prevalence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and seasonal human coronaviruses(HCoV)like HCoV-OC43,HCoV-NL63,and HCoV-229E,pose a continuous threat to public heal...The established and ongoing prevalence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and seasonal human coronaviruses(HCoV)like HCoV-OC43,HCoV-NL63,and HCoV-229E,pose a continuous threat to public health.Therefore,it is urgently needed to explore antiviral drugs with broad-spectrum anti-coronavirus activity.Our previous studies have revealed that lycorine is a potent broad-spectrum anti-coronavirus drug,a natural alkaloid extracted from Amaryllidaceae with various pharmacological and microbiological effects.However,it is unsafe to directly use lycorine as a clinical antiviral drug due to the cytotoxicity and induction of cell apoptosis.In this study,a series of lycorine derivatives were designed and synthesized.One of them,named Ly-8,was found to effectively inhibit the replication of different coronavirus strains in vitro,including SARS-CoV-2.Moreover,Ly-8 was also shown to effectively inhibit HCoVOC43 replication in the central nervous system,and provide effective protection against HCoV-OC43 infection in mice with low drug toxicity.Furthermore,Ly-8-resistant mutants were not observed during the 30 times sequential passages in cell culture.Collectively,these findings suggest that Ly-8 may be a potential candidate drug for the future development of broad-spectrum anti-coronavirus drugs.展开更多
基金supported by the Fujian Minimally Invasive Medical Center Foundation,No.2128100514(to CC,CW,HX)the Natural Science Foundation of Fujian Province,No.2023J01640(to CC,CW,ZL,HX)。
文摘Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.
文摘Although there are challenges in treating traumatic central nervous system diseases,mesenchymal stem cell-de rived extracellular vesicles(MSC-EVs) have recently proven to be a promising non-cellular the rapy.We comprehensively evaluated the efficacy of mesenchymal stem cell-de rived extracellular vesicles in traumatic central nervous system diseases in this meta-analysis based on preclinical studies.Our meta-analysis was registered at PROSPERO(CRD42022327904,May 24,2022).To fully retrieve the most relevant articles,the following databases were thoro ughly searched:PubMed,Web of Science,The Cochrane Library,and Ovid-Embase(up to April 1,2022).The included studies were preclinical studies of mesenchymal stem cell-derived extracellular vesicles for traumatic central nervous system diseases.The Systematic Review Centre for Laboratory Animal Experimentation(SYRCLE)’s risk of bias tool was used to examine the risk of publication bias in animal studies.After screening 2347studies,60 studies were included in this study.A meta-analysis was conducted for spinal co rd injury(n=52) and traumatic brain injury(n=8).The results indicated that mesenchymal stem cell-derived extracellular vesicles treatment prominently promoted motor function recovery in spinal co rd injury animals,including rat Basso,Beattie and Bresnahan locomotor rating scale scores(standardized mean difference [SMD]:2.36,95% confidence interval [CI]:1.96-2.76,P <0.01,I2=71%) and mouse Basso Mouse Scale scores(SMD=2.31,95% CI:1.57-3.04,P=0.01,I2=60%) compared with controls.Further,mesenchymal stem cell-de rived extracellular vesicles treatment significantly promoted neurological recovery in traumatic brain injury animals,including the modified N eurological Severity Score(SMD=-4.48,95% CI:-6.12 to-2.84,P <0.01,I2=79%) and Foot Fault Test(SMD=-3.26,95% CI:-4.09 to-2.42,P=0.28,I2=21%) compared with controls.Subgroup analyses showed that characteristics may be related to the therapeutic effect of mesenchymal stem cell-de rived extra cellular vesicles.For Basso,Beattie and Bresnahan locomotor rating scale scores,the efficacy of allogeneic mesenchymal stem cell-derived extracellular vesicles was higher than that of xenogeneic mesenchymal stem cell-derived extracellular vesicles(allogeneic:SMD=2.54,95% CI:2.05-3.02,P=0.0116,I2=65.5%;xenogeneic:SMD:1.78,95%CI:1.1-2.45,P=0.0116,I2=74.6%).Mesenchymal stem cellde rived extracellular vesicles separated by ultrafiltration centrifugation combined with density gradient ultra centrifugation(SMD=3.58,95% CI:2.62-4.53,P <0.0001,I2=31%) may be more effective than other EV isolation methods.For mouse Basso Mouse Scale scores,placenta-derived mesenchymal stem cell-de rived extracellular vesicles worked better than bone mesenchymal stem cell-derived extracellular vesicles(placenta:SMD=5.25,95% CI:2.45-8.06,P=0.0421,I2=0%;bone marrow:SMD=1.82,95% CI:1.23-2.41,P=0.0421,I2=0%).For modified Neurological Severity Score,bone marrow-derived MSC-EVs worked better than adipose-derived MSC-EVs(bone marrow:SMD=-4.86,95% CI:-6.66 to-3.06,P=0.0306,I2=81%;adipose:SMD=-2.37,95% CI:-3.73 to-1.01,P=0.0306,I2=0%).Intravenous administration(SMD=-5.47,95% CI:-6.98 to-3.97,P=0.0002,I2=53.3%) and dose of administration equal to 100 μg(SMD=-5.47,95% CI:-6.98 to-3.97,P <0.0001,I2=53.3%)showed better res ults than other administration routes and doses.The heterogeneity of studies was small,and sensitivity analysis also indicated stable results.Last,the methodological quality of all trials was mostly satisfactory.In conclusion,in the treatment of traumatic central nervous system diseases,mesenchymal stem cell-derived extracellular vesicles may play a crucial role in promoting motor function recovery.
基金financially supported by the National Natural Science Foundation of China(52072101,51972088,U20A20122 and U1663225)the Program for Changjiang Scholars and Innovative Research Team in University(IRT_15R52)of the Chinese Ministry of Education+2 种基金the Program of Introducing Talents of Discipline to Universities-Plan 111(Grant No.B20002)from the Ministry of Science and Technology and the Ministry of Education of ChinaHubei Provincial Department of Education for the“Chutian Scholar”programsupported by the European Commission Interreg V FranceWallonie-Vlaanderen project“Depollut Air”。
文摘Owing to their high luminous efficiency and tunable emission in both red light and far-red light regions,Mn^(4+)ion-activated phosphors have appealed significant interest in photoelectric and energy conversion devices such as white light emitting diode(W-LED),plant cultivation LED,and temperature thermometer.Up to now,Mn^(4+)has been widely introduced into the lattices of various inorganic hosts for brightly redemitting phosphors.However,how to correlate the structure-activity relationship between host framework,luminescence property,and photoelectric device is urgently demanded.In this review,we thoroughly summarize the recent advances of Mn^(4+)doped phosphors.Meanwhile,several strategies like co-doping and defect passivation for improving Mn^(4+)emission are also discussed.Most importantly,the relationship between the protocols for tailoring the structures of Mn^(4+)doped phosphors,increased luminescence performance,and the targeted devices with efficient photoelectric and energy conversion efficiency is deeply correlated.Finally,the challenges and perspectives of Mn^(4+)doped phosphors for practical applications are anticipated.We cordially anticipate that this review can deliver a deep comprehension of not only Mn^(4+)luminescence mechanism but also the crystal structure tailoring strategy of phosphors,so as to spur innovative thoughts in designing advanced phosphors and deepening the applications.
基金financially supported by the National Natural Science Foundation of China (21902132)the Research Foundation-Flanders (1280021N, 1242922N, 1298323N)。
文摘Gold(Au) nanostructures(NSs) have been widely employed as cocatalysts to improve the photoactivity of semiconductor materials, while a systematic summary of the engineering approaches of Au NSs to maximize the solar-to-fuel conversion efficiency is still lacking. In this review, the recently developed strategies for elevating the overall photocatalytic performance of Au-based catalysts and the deep physical chemistry mechanisms are highlighted. Firstly, the synthetic approaches of Au NSs are summarized, followed by an elaboration on their multiple functions in improving photoactivity. Afterward, modification strategies of Au NSs used to enhance the photocatalytic efficiency of Au-semiconductor composites,including controlling the Au NSs morphology, size, crystal phase, defect engineering, alloying with different metals, modulating interfacial interaction, and introducing an external field, are summarized and discussed independently. Additionally, advanced characterization techniques that can provide insights into the charge dynamics of the photocatalysts are introduced. Finally, we share our opinion on the challenges and outline potentially promising opportunities and directions for efficient Au-based photocatalysis research moving forward. We sincerely look forward to this review can deliver insightful views to design efficient Au-based photocatalysts and spur certain innovations to other metal-based catalysts.
文摘<strong>Objective</strong>: This paper aims to explore clinical status and related influence factors of pressure injury (PI) in the elderly inpatients with kidney disease, so as to provide reference for the prevention and treatment of PI in the elderly inpatients with kidney disease. <strong>Methods</strong>: Retrospective collection method is adopted to collect 158 clinical cases of the elderly inpatients with kidney disease aged ≥ 60 in the Nephrology Department, the First Affiliated Hospital of Jinan University from January 2017 to December 2019, and then least absolute shrinkage and selection Operator (LASSO) regression analysis is used to analyze 17 possible influence factors;finally Logistic regression model is established to analyze and screen influence factors of risk. <strong>Results</strong>: 1) Among 158 elderly inpatients with medium and high risk of PI, the incidence of PI is 20.25%;the most common stage of injury is stage I (42.5%);sacrococcygeal (60%) is the high-risk site of pressure injury. 2) LASSO regression analysis shows that history of present respiratory infection/respiratory failure (<em>β </em>= 1.2714. <em>P</em> < 0.05) and hospitalization time (<em>β</em> = 0.4177. <em>P </em>< 0.05) are independent factors influencing PI risk in the elderly inpatients with kidney disease. <strong>Concl</strong><strong>usio</strong><strong>n</strong>: The elderly patients with kidney disease and PI risk are the high incidence population of hospital acquired PI;for the elderly inpatients with kidney disease and having respiratory infection history or respiratory failure, prolonged hospitalization will significantly increase the risk of PI. Therefore, targeted preventive and control measures should be taken to reduce the incidence of PI.
基金supported by the Technology Project of the Department of Education of Fujian Province of China,No.JA10144
文摘Inducible nitric oxide synthase and N-methyI-D-aspartate receptors have been shown to participate in nerve cell injury during spinal cord ischemia. This study observed a protective effect of curcumin on ischemic spinal cord injury. Models of spinal cord ischemia were established by ligating the lumbar artery from the left renal artery to the bifurcation of the abdominal aorta. At 24 hours after model establishment, the rats were intraperitoneally injected with curcumin, Reverse transcrip- tion-polymerase chain reaction and immunohistochemical results demonstrated that after spinal cord ischemia, inducible nitric oxide synthase and N-methyI-D-aspartate receptor mRNA and protein expression significantly increased. However, curcumin significantly decreased inducible nitric oxide synthase and N-methyI-D-aspartate receptor mRNA and protein expression in the ischemic spinal cord. Tadov scale results showed that curcumin significantly improved motor function of the rat hind limb after spinal cord ischemia. The results demonstrate that curcumin exerts a neuroprotective ef- fect against ischemic spinal cord injury by decreasing inducible nitric oxide synthase and N-methyI-D-aspartate receptor expression.
基金Hunan Provincial Natural Science Foundation of China (No. 06JJ50103)the National Natural Science Foundationof China (No. 60375001)
文摘Based on results of chaos characteristics comparing one-dimensional iterative chaotic self-map x = sin（2/x） with infinite collapses within the finite region[-1, 1] to some representative iterative chaotic maps with finite collapses （e.g., Logistic map, Tent map, and Chebyshev map）, a new adaptive mutative scale chaos optimization algorithm （AMSCOA） is proposed by using the chaos model x = sin（2/x）. In the optimization algorithm, in order to ensure its advantage of speed convergence and high precision in the seeking optimization process, some measures are taken： 1） the searching space of optimized variables is reduced continuously due to adaptive mutative scale method and the searching precision is enhanced accordingly; 2） the most circle time is regarded as its control guideline. The calculation examples about three testing functions reveal that the adaptive mutative scale chaos optimization algorithm has both high searching speed and precision.
基金financially supported by the National Natural Science Foundation of China(U1663225)the Changjiang Scholar Program of Chinese Ministry of Education(IRT15R52)the program of Introducing Talents of Discipline to Universities-Plan 111(B20002)of Ministry of Science and Technology and the Ministry of Education of China and the project “Depollut Air”of Interreg V France-WallonieVlaanderen。
文摘Graphitic carbon nitride(g-C_(3)N_(4))has attracted great interest in photocatalysis and photoelectrocatalysis.However,their poor hydrophilicity poses a great challenge for their applications in aqueous environment.Here,we demonstrate synthesis of a hydrophilic bi-functional hierarchical architecture by the assembly of B-doped g-C_(3)N_(4)nanoplatelets.Such hierarchical B-doped g-C_(3)N_(4)material enables full utilization of their highly enhanced visible light absorption and photogenerated carrier separation in aqueous medium,leading to an excellent photocatalytic H_(2)O_(2)production rate of 4240.3μM g^(-1)h^(-1),2.84,2.64 and 2.13 times higher than that of the bulk g-C_(3)N_(4),g-C_(3)N_(4)nanoplatelets and bulk B doped g-C_(3)N_(4),respectively.Photoanodes based on these hierarchical architectures can generate an unprecedented photocurrent density of 1.72 m A cm^(-2)at 1.23 V under AM 1.5 G illumination for photoelectrochemical water splitting.This work makes a fundamental improvement towards large-scale exploitation of highly active,hydrophilic and stable metal-free g-C_(3)N_(4)photocatalysts for various practical applications.
文摘Studies have shown that estrogen has neuroprotective effects on the nigrostriatal system. The present study established a Parkinson＇s disease model in C57BL/6 mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrapyridine. The mice were subjected to 1713 estradiol injection into the lateral ventricle. Immunofluorescence double staining showed that estrogen increased tyrosine hydroxylase and calbindin-D28K expression and co-expression in dopaminergic neurons of midbrain substantia nigra pars compacta of model mice. Behavior experiments showed that estrogen improved swimming and hanging behaviors in this mouse model of Parkinson＇s disease.
基金partially supported by NSFC(11671162,11601194)CCNU18CXTD04 and CZQ13017。
文摘In this paper, we consider the following coupled Schrodinger system with χ^(2) nonlinearities {-Δu1+V1(x)u1=αu1u2,x∈R^N,-Δu2+V2(x)u2=α/2u^21+βu^22,x∈R^N.which arises from second-harmonic generation in quadratic media. Here V1(x) and V2(x) are radially positive functions, 2 ≤ N < 6, α > 0 and α > β. Assume that the potential functions V1(x) and V2(x) satisfy some algebraic decay at infinity. Applying the finite dimensional reduction method, we construct an unbounded sequence of non-radial vector solutions of synchronized type.
基金funded by the National Key Research and Development Program for Breeding Seven Key Crops(2016YFD0101700)the Academic Backbone Project of Northeast Agricultural University(18XG06)+1 种基金the Heilongjiang Postdoctoral Scientific Research Developmental Fund(LBHQ16021)the Natural Science Foundation of Heilongjiang Province,China(LH2019C033).
文摘Fruit curving lowers the commercial value of cucumber and leads to significant economic losses.The mechanism driving the abnormal curving of cucumber is largely unknown.Through our previous work,we discovered that 2 days post-anthesis(DPA)was the key time point at which various phenotypic and genotypic characteristics of cucumber fruits are determined.Here,we analyzed the transcriptome of the concave(C1)and convex(C2)sides of curved fruits at 2 DPA by Gene Ontology(GO)enrichment and functional pathway enrichment analyses and identified auxin as a putative factor influencing fruit curvature.Changes in the curve angle in the fruits and exogenous auxin treatment analyses showed that asymmetric auxin distribution induces fruit curving.Identification of differentially expressed genes(DEGs)related to auxin and qPCR validation showed that CsYUC10b had the most significant differential expression when both sides of the curved fruits were compared.Gene functional analysis showed that the transcript levels of CsYUC10b and the auxin concentration were even on both sides of the fruit in CsYUC10b-overexpressing plants,which in turn contributed to an equal rate of growth of both sides of cucumber fruits and resulted in a straight shape of the fruits.Thus,we conclude that CsYUC10b promotes the formation of straight cucumber fruits,with possible applications in the production and breeding of cucumber.
基金supported by the National Natural Science Foundation of China, No. 81100987the Natural Science Foundation of Fujian Province of China, No.2011J05066the Clinical Key Subject (Neurosurgery) Funding of Fujian Medical University
文摘Ischemic stroke induces a series of complex pathophysiological events including blood-brain barrier disruption, inflammatory response and neuronal apoptosis. Previous studies demonstrate that ischemic preconditioning attenuates ischemic brain damage via inhibiting blood-brain barrier disruption and the inflammatory response. Rats underwent transient （15 minutes） occlusion of the bilateral common carotid artery with 48 hours of reperfusion, and were subjected to permanent middle cerebral artey occlusion. This study explored whether ischemic preconditioning could reduce ischemic brain injury and relevant molecular mechanisms by inhibiting neuronal apoptosis. Results found that at 72 hours following cerebral ischemia, myeloperoxidase activity was enhanced, malondialdehyde levels increased, and neurological function was obviously damaged. Simultaneously, neuronal apoptosis increased, and nuclear factor-KB and cleaved caspase-3 expression was significantly increased in ischemic brain tissues. Ischemic preconditioning reduced the cerebral ischemia-induced inflammatory response, lipid peroxidation, and neurological function injury. In addition, ischemic preconditioning decreased nuclear factor-KB p65 and cleaved caspase-3 expression. These results suggested that ischemic preconditioning plays a protective effect against ischemic brain injury by suppressing the inflammatory response, reducing lipid peroxidation, and neuronal apoptosis via inhibition of nuclear factor-KB and cleaved caspase-3 expression.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.91850107 and 12174116)the National Key Research and Development Program of China(Grant No.2018YFA0306200)+3 种基金Guangdong Innovative and Entrepreneurial Research Team Program(Grant No.2016ZT06C594)the Key Program of Guangzhou Scientific Research Special Project(Grant No.201904020013)the Science and Technology Project of Guangdong Province,China(Grant No.2020B010190001)the Fundamental Research Funds for the Central Universities。
文摘Here we propose a hybrid polymer-LN waveguide for achieving phase-matched second-harmonic generation(SHG).From the aspect of super-mode theory,the geometric parameters of the hybrid semi-nonlinear waveguide were optimized to utilize both symmetric(even)and antisymmetric(odd)modes of the pump and SHG waves so as to facilitate phase matching with large modal overlap.Phase matching between a fundamental even(TE_(00)-like)mode at 1320 nm and a fundamental odd(TE_(01)-like)mode at 660 nm was found with a calculated modal overlap integral of 0.299,while utilizing the largest nonlinear coefficient d_(33),and achieving an efficient calculated normalized conversion efficiency of 148%W^(-1)·cm^(-2).Considering the fabrication feasibility of such hybrid waveguide with features including etchless,large dimension,and low structural sensitivity,we believe our findings would provide a useful reference for future on-chip efficient nonlinear conversion devices.
文摘Purpose: To explore the fever-related risk factors of inpatients in Rehabilitation Department, and to provide reference for patients with high risk of fever to take corresponding nursing measures. Methods: The study was conducted on the Rehabilitation Department of The First Affiliated Hospital of Jinan University from July 2019 to December 2019. The fever group included 51 patients and the non-fever group included 49 patients without fever. The two groups of clinical data, comorbidities, related laboratory values, possible risk factors of fever were analyzed by case regression analysis, and the relevant risk factors were screened out by LASSO (least absolute shrinkage and selection operator) regression analysis. Results: According to the results of Lasso regression analysis, pressure sore or skin infection, history of hypertension, current history of respiratory tract infection, feeding patterns were the higher risk factors of fever in inpatients in Rehabilitation Department, while the first course of disease, main diagnosis, history of respiratory tract infection within half a year, kidney damage and hospitalization days were lower risk factors. Conclusion: This study is helpful to early identify the fever risk of inpatients in Rehabilitation Department, and provide reference basis for high-risk fever patients to take positive and effective nursing measures.
基金supported by the Fundamental Research Funds for the Central Universities(2232019A3-07,2232019D3-20)the Science and Technology Commission of Shanghai Municipality(20S31900900,20DZ2254900)+8 种基金the Sino German Science Foundation Research Exchange Center(M0263)the National Natural Science Foundation of China(82102579,81871753)the Shanghai Rising-Star Program(22QC1401200)the Basic Scientific Research Project of Shanghai Sixth People’s Hospital(ynqn202101)the Opening Project of National Engineering Laboratory for Modern Silk,Soochow University(SDGC2149)the National Key Research and Development Program of China(2018YFC1106200,2018YFC1106202)the Key R&D Program of Shandong province(2019JZZY011104)the Deutsche Forschungsgemeinschaft(German Research Foundation(B.R.:RO 2511/11-1),This project was also supported by Researchers Supporting Project Number(RSP2023R65)King Saud University,Riyadh,Saudi Arabia,and the combined Sino-German Mobility Programme of the National Natural Science Foundation of China(NSFC)/Deutsche Forschungsgemeinschaft(German Research Foundation(B.R.:M0332).
文摘The escalating prevalence of anterior cruciate ligament(ACL)injuries in sports necessitates innovative strategies for ACL reconstruction.In this study,we propose a multiphasic bone-ligament-bone(BLB)integrated scaffold as a potential solution.The BLB scaffold comprised two polylactic acid(PLA)/deferoxamine(DFO)@mesoporous hydroxyapatite(MHA)thermally induced phase separation(TIPS)scaffolds bridged by silk fibroin(SF)/connective tissue growth factor(CTGF)@Poly(L-lactide-co-ε-caprolactone)(PLCL)nanofiber yarn braided scaffold.This combination mimics the native architecture of the ACL tissue.The mechanical properties of the BLB scaffolds were determined to be compatible with the human ACL.In vitro experiments demonstrated that CTGF induced the expression of ligament-related genes,while TIPS scaffolds loaded with MHA and DFO enhanced the osteogenic-related gene expression of bone marrow stem cells(BMSCs)and promoted the migration and tubular formation of human umbilical vein endothelial cells(HUVECs).In rabbit models,the BLB scaffold efficiently facilitated ligamentization and graft-bone integration processes by providing bioactive substances.The double delivery of DFO and calcium ions by the BLB scaffold synergistically promoted bone regeneration,while CTGF improved collagen formation and ligament healing.Collectively,the findings indicate that the BLB scaffold exhibits substantial promise for ACL reconstruction.Additional investigation and advancement of this scaffold may yield enhanced results in the management of ACL injuries.
基金supported by National Natural Science Foundation of China(82002192)Natural Science Foundation of Hubei Province(2022CFB539,2022CFD107)+2 种基金Young and middle-aged Talents Project of Hubei Provincial Education Department(Q20222605)Scientific Research Ability Cultivation Fund of Hubei University of Arts and Science(2021KPGJ06)Science and Technology Plan(in the field of Medical and health care)of Xiangyang(2022YL05B,2022YL12A).
文摘In 2022,a global outbreak of Mpox(formerly monkeypox)occurred in various countries across Europe and America and rapidly spread to more than 100 countries and regions.The World Health Organization declared the outbreak to be a public health emergency of international concern due to the rapid spread of the Mpox virus.Consequently,nations intensified their efforts to explore treatment strategies aimed at combating the infection and its dissemination.Nevertheless,the available therapeutic options for Mpox virus infection remain limited.So far,only a few numbers of antiviral compounds have been approved by regulatory authorities.Given the high mutability of the Mpox virus,certain mutant strains have shown resistance to existing pharmaceutical interventions.This highlights the urgent need to develop novel antiviral drugs that can combat both drug resistance and the potential threat of bioterrorism.Currently,there is a lack of comprehensive literature on the pathophysiology and treatment of Mpox.To address this issue,we conducted a review covering the physiological and pathological processes of Mpox infection,summarizing the latest progress of anti-Mpox drugs.Our analysis encompasses approved drugs currently employed in clinical settings,as well as newly identified small-molecule compounds and antibody drugs displaying potential antiviral efficacy against Mpox.Furthermore,we have gained valuable insights from the process of Mpox drug development,including strategies for repurposing drugs,the discovery of drug targets driven by artificial intelligence,and preclinical drug development.The purpose of this review is to provide readers with a comprehensive overview of the current knowledge on Mpox.
基金supported by National Natural Science Foundation of China (82002192,32302218)General project of Natural Science Foundation of Hubei Province (2019CFA016,2022CFB539,2022CFD107)+3 种基金Young and Middle-aged Talents Project of Hubei Provincial Education Department (Q20222605)Tianjin Municipal Science and Technology Committee (21JCQNJC01410)China Postdoctoral Science Foundation (2021M702460)Science and Technology Plan (in the field of medical and health care)of Xiangyang (2022YL05B,2022YL12A).
文摘The established and ongoing prevalence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and seasonal human coronaviruses(HCoV)like HCoV-OC43,HCoV-NL63,and HCoV-229E,pose a continuous threat to public health.Therefore,it is urgently needed to explore antiviral drugs with broad-spectrum anti-coronavirus activity.Our previous studies have revealed that lycorine is a potent broad-spectrum anti-coronavirus drug,a natural alkaloid extracted from Amaryllidaceae with various pharmacological and microbiological effects.However,it is unsafe to directly use lycorine as a clinical antiviral drug due to the cytotoxicity and induction of cell apoptosis.In this study,a series of lycorine derivatives were designed and synthesized.One of them,named Ly-8,was found to effectively inhibit the replication of different coronavirus strains in vitro,including SARS-CoV-2.Moreover,Ly-8 was also shown to effectively inhibit HCoVOC43 replication in the central nervous system,and provide effective protection against HCoV-OC43 infection in mice with low drug toxicity.Furthermore,Ly-8-resistant mutants were not observed during the 30 times sequential passages in cell culture.Collectively,these findings suggest that Ly-8 may be a potential candidate drug for the future development of broad-spectrum anti-coronavirus drugs.
基金the financial support from the China Scholarship Council(201808310127)Hubei Provincial Department of Education for the“Chutian Scholar”program+2 种基金financially supported by the Foundation of Natural Science(61905159)the National Natural Science Foundation of China(U1663225)Program for Changjiang Scholars and Innovative Research Team(IRT_15R52)the project“Depollut Air”of Interreg V France-Wallonie-Vlaanderen。
