Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we...Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.展开更多
Triboelectric nanogenerators(TENG),renowned for their remarkable capability to harness weak mechanical energy from the environment,have gained considerable attention owing to their cost-effectiveness,high output,and a...Triboelectric nanogenerators(TENG),renowned for their remarkable capability to harness weak mechanical energy from the environment,have gained considerable attention owing to their cost-effectiveness,high output,and adaptability.This review provides a unique perspective by conducting a comprehensive and in-depth analysis of magnetically assisted TENGs that encompass structures,materials,and self-powered sensing systems.We systematically summarize the diverse functions of the magnetic assistance for TENGs,including system stiffness,components of the hybrid electromagnetic-triboelectric generator,transmission,and interaction forces.In the material domain,we review the incorporation of magnetic nano-composites materials,along with ferrofluid-based TENG and microstructure verification,which have also been summarized based on existing research.Furthermore,we delve into the research progress on physical quantity sensing and human-machine interface in magnetic-assisted TENGs.Our analysis highlights that magnetic assistance extends beyond the repulsive and suction forces under a magnetic field,thereby playing multifaceted roles in improving the output performance and environmental adaptability of the TENGs.Finally,we present the prevailing challenges and offer insights into the future trajectory of the magnetic-assisted TENGs development.展开更多
Maintaining the integrity of the blood-spinal cord barrier is critical for the recove ry of spinal cord injury.Ferro ptosis contributes to the pathogenesis of spinal cord injury.We hypothesized that ferroptosis is inv...Maintaining the integrity of the blood-spinal cord barrier is critical for the recove ry of spinal cord injury.Ferro ptosis contributes to the pathogenesis of spinal cord injury.We hypothesized that ferroptosis is involved in disruption of the blood-s pinal cord barrier.In this study,we administe red the ferroptosis inhibitor liproxstatin-1 intraperitoneally after contusive spinal co rd injury in rats.Liproxstatin-1 improved locomotor recovery and somatosensory evoked potential electrophysiological performance after spinal cord inju ry.Liproxstatin-1 maintained blood-spinal cord barrier integrity by upregulation of the expression of tight junction protein.Liproxstatin-1 inhibited ferroptosis of endothelial cell after spinal cord injury,as shown by the immunofluorescence of an endothelial cell marker(rat endothelium cell antigen-1,RECA-1) and fe rroptosis markers Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase.Liproxstatin-1reduced brain endothelial cell ferroptosis in vitro by upregulating glutathione peroxidase 4 and downregulating Acyl-CoA synthetase long-chain family member4 and 15-lipoxygenase.Furthermore,inflammatory cell recruitment and astrogliosis were mitigated after liproxstatin-1 treatment.In summary,liproxstatin-1im proved spinal cord injury recovery by inhibiting ferroptosis in endothelial cells and maintaining blood-s pinal co rd barrier integrity.展开更多
Due to flexible deployment,unmanned aerial vehicle(UAV)mounted aerial access points are capable of expanding the coverage capabilities of existing terrestrial base stations(TBSs).Different from TBSs,however,UAV access...Due to flexible deployment,unmanned aerial vehicle(UAV)mounted aerial access points are capable of expanding the coverage capabilities of existing terrestrial base stations(TBSs).Different from TBSs,however,UAV access points(UAPs)are of high mobility in horizontal and vertical dimensions,which may deteriorate the coverage performance.Worsestill,the mobility of UAPs would as well increase the pressure of wireless backhaul.In this light,we investigate the performance of the cache-enabled UAV communications network(CUCN)in terms of network spatial throughput(ST)by analyzing the line of sight(LoS)connections and non-line of sight(NLoS)connections.It is found that the network ST is exponentially decreased with the square of UAP altitude.Furthermore,contrary to intuition,a large cache size may deteriorate the network ST when UAPs are over-deployed.The reason is that a large cache size increases the hit probability,which may increase the activation of UAPs and consequently result in complicated interference.Aiming to maximize the network ST,we optimize the cache strategy under limited backhaul.Remarkably,the results show that network ST could be substantially improved by the optimized cache strategy and the performance degeneration brought by UAP high mobility could be even eliminated especially when the UAP altitude is high.展开更多
The construction and application of novel highly efficient photocatalysts have been the focus in the field of environmental pollutant removal.In this work,a novel CuFe_(2)O_(4)/Bi_(12)O_(17)Cl_(2)photocatalysts were s...The construction and application of novel highly efficient photocatalysts have been the focus in the field of environmental pollutant removal.In this work,a novel CuFe_(2)O_(4)/Bi_(12)O_(17)Cl_(2)photocatalysts were synthesized by simple hydrothermal and chemical precipitation method.The fabricated CuFe_(2)O_(4)/Bi_(12)O_(17)Cl_(2)composite exhibited much higher photocatalytic activity than pristine CuFe_(2)O_(4)and Bi_(12)O_(17)Cl_(2)in the removal of bisphenol A(BPA)under visible-light illumination,which ascribed to the intrinsic p-n junction of CuFe_(2)O_(4)and Bi_(12)O_(17)Cl_(2).The photocatalytic degradation rate of BPA on CuFe_(2)O_(4)/Bi_(12)O_(17)Cl_(2)with an optimized CuFe_(2)O_(4)content(1.0 wt.%)reached 93.0%within 30 min.The capture experiments of active species confirmed that the hydroxyl radicals(·OH)and superoxide radicals(·O_(2)^(-))played crucial roles in photocatalytic BPA degradation process.Furthermore,the possible degradation mechanism and pathways of BPA was proposed according to the detected intermediates in photocatalytic reaction process.展开更多
Chiral chemicals have attracted significant interest in the pharmaceutical industry,yet the separation methods to get pure enantiomers from racemic mixture are still challenging.To date,the separation of enantiomers s...Chiral chemicals have attracted significant interest in the pharmaceutical industry,yet the separation methods to get pure enantiomers from racemic mixture are still challenging.To date,the separation of enantiomers still mainly depends on chromatography using high-cost chiral stationary phases.Herein,wood channels were used as the handheld integrated device,and enantiomer separation was simultaneously detected using an electrochemical detector.In this method,a chiral UIO-66(L-UIO-66)modified enantiomer separation zone and carbonized wood based online detection zone are integrated along a single wood column.Based on the in situ separation results from the chronoamperometry data,the wood device shows excellent separation ability for a wide range of electrochemically active enantiomers,including 3,4-dihydroxyphenylalanine,amino acids,ascorbic acid,carnitine,and penicillamine with high chirality purity.The unbiased molecular dynamic simulations indicate that the excellent chiral recognition and separation are attributed to the different barriers from the bound states to the dissociated state of the enantiomers in the homochiral microenvironment of the framework.This integrated enantiomer separation-electrochemical detection device provides a novel,easy,and low-cost platform for the separation of pure enantiomer from racemic mixture.展开更多
Spinal cord injury(SCI)is a traumatic condition that results in impaired motor and sensory function.Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord,and f...Spinal cord injury(SCI)is a traumatic condition that results in impaired motor and sensory function.Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord,and ferroptosis inhibitors are effective in reducing inflammation and repairing SCI.Although human umbilical cord mesenchymal stem cells(Huc-MSCs)can ameliorate inflammatory microenvironments and promote neural regeneration in SCI,their efficacy is greatly limited by the local microenvironment after SCI.Therefore,in this study,we constructed a drug-release nanoparticle system with synergistic Huc-MSCs and ferroptosis inhibitor,in which we anchored Huc-MSCs by a Tz-A6 peptide based on the CD44-targeting sequence,and combined with the reactive oxygen species(ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at the other end for SCI repair.Meanwhile,we also modified the classic ferroptosis inhibitor Ferrostatin-1(Fer-1)and synthesized a new prodrug Feborastatin-1(Feb-1).The results showed that this treatment regimen significantly inhibited the ferroptosis and inflammatory response after SCI,and promoted the recovery of neurological function in rats with SCI.This study developed a combination therapy for the treatment of SCI and also provides a new strategy for the construction of a drug-coordinated cell therapy system.展开更多
In response to problems of poor sampling quality,low sensitivity,and high demand for medical personnel regarding the current severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)oropharyngeal(OP)swab sampling us...In response to problems of poor sampling quality,low sensitivity,and high demand for medical personnel regarding the current severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)oropharyngeal(OP)swab sampling used in China,we aimed to evaluate the diagnostic performance and acceptability of saliva-based nucleic acid amplification tests(NAATs)in China.The results showed that,using nasopharyngeal(NP)swab results as the gold standard,the overall sensitivities for saliva specimens and OP swabs were 93.3%and 85.0%,the specificities were 92.6%and 93.8%,respectively.The results of an acceptability survey showed that the scores for saliva,OP,and NP samples were 9.46±1.69,8.11±2.42,and 4.58±3.82 out of 10,respectively,with significant differences among the three groups(P<0.05).With higher sensitivity,comparable specificity,and strong public preference,saliva-based NAATs represent a convenient and effective method for detecting SARS-CoV-2 in future epidemics.展开更多
Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths worldwide.Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable fo...Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths worldwide.Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable for and beneficial to a mere~30%of NSCLC patients.Consequently,the need for novel strategies addressing NSCLC remains pressing.Deubiquitinases(DUBs),a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic targets.Nevertheless,the mechanisms by which DUBs promote NSCLC remain poorly understood.Through a global analysis of the 97 DUBs’contribution to NSCLC survival possibilities using The Cancer Genome Atlas(TCGA)database,we found that high expression of Josephin Domain-containing protein 2(JOSD2)predicted the poor prognosis of patients.Depletion of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in vivo.Mechanically,we found that JOSD2 restricts the kinase activity of LKB1,an important tumor suppressor generally inactivated in NSCLC,by removing K6-linked polyubiquitination,an action vital for maintaining the integrity of the LKB1-STRAD-MO25 complex.Notably,we identified the first small-molecule inhibitor of JOSD2,and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in vivo.Our findings highlight the vital role of JOSD2 in hindering LKB1 activity,underscoring the therapeutic potential of targeting JOSD2 in NSCLC,especially in those with inactivated LKB1,and presenting its inhibitors as a promising strategy for NSCLC treatment.展开更多
Regulation of perovskite growth plays a critical role in the development of high-performance optoelectronic devices.However,judicious control of the grain growth for perovskite light emitting diodes is elusive due to ...Regulation of perovskite growth plays a critical role in the development of high-performance optoelectronic devices.However,judicious control of the grain growth for perovskite light emitting diodes is elusive due to its multiple requirements in terms of morphology,composition,and defect.Herein,we demonstrate a supramolecular dynamic coordination strategy to regulate perovskite crystallization.The combined use of crown ether and sodium trifluoroacetate can coordinate with A site and B site cations in ABX_(3) perovskite,respectively.The formation of supramolecular structure retard perovskite nucleation,while the transformation of supramolecular intermediate structure enables the release of components for slow perovskite growth.This judicious control enables a segmented growth,inducing the growth of insular nanocrystal consist of low-dimensional structure.Light emitting diode based on this perovskite film eventually brings a peak external quantum efficiency up to 23.9%,ranking among the highest efficiency achieved.The homogeneous nano-island structure also enables high-efficiency large area(1 cm^(2))device up to 21.6%,and a record high value of 13.6%for highly semi-transparent ones.展开更多
In this work,a novel dual Z-scheme Bi_(2)WO_(6)/g-C_(3)N_(4)/black phosphorus quantum dots(Bi_(2)WO_(6)/g-C_(3)N_(4)/BPQDs)composites were fabricated and utilized towards photocatalytic degradation of bisphenol A(BPA)...In this work,a novel dual Z-scheme Bi_(2)WO_(6)/g-C_(3)N_(4)/black phosphorus quantum dots(Bi_(2)WO_(6)/g-C_(3)N_(4)/BPQDs)composites were fabricated and utilized towards photocatalytic degradation of bisphenol A(BPA)under visible-light irradiation.Optimizing the content of g-C_(3)N_(4) and BPQDs in Bi_(2)WO_(6)/g-C_(3)N_(4)/BPQDs composites to a suitable mass ratio can enhance the visible-light harvesting capacity and increase the charge separation efficiency and the transfer rate of excited-state electrons and holes,resulting in much higher photocatalytic activity for BPA degradation(95.6%,at 20 mg/L in 120 min)than that of Bi2WO6(63.7%),g-C_(3)N_(4)(25.0%),BPQDs(8.5%),and Bi_(2)WO_(6)/g-C_(3)N_(4)(79.6%),respectively.Radical trapping experiments indicated that photogenerated holes(h+)and superoxide radicals(•O_(2)−)played crucial roles in photocatalytic BPA degradation.Further,the possible degradation pathway and photocatalytic mechanism was proposed by analyzing the BPA intermediates.Thiswork also demonstrated that the Bi2WO6/g-C_(3)N_(4)/BPQDs as effective photocatalystswas stable and have promising potential to remove environmental contaminants from real water samples.展开更多
During the Coronavirus disease(COVID-19),the physical activity of older adults is at a lower level.The study aimed to examine the effectiveness of aerobic dancing on physical fitness and cognitive function in older ad...During the Coronavirus disease(COVID-19),the physical activity of older adults is at a lower level.The study aimed to examine the effectiveness of aerobic dancing on physical fitness and cognitive function in older adults.We conducted a randomized controlled trial with 34 older adults who were assigned into an aerobic dancing group and a control group.Three dance sessions weekly for 60min were scheduled for the aerobic dancing group for a total of 12 weeks.Physical fitness,blood pressure,lipids,glucose,cognitive function were assessed before and after the intervention.Baseline adjusted Analysis of Covariance(ANCOVA)was used to determine whether outcome variables varied between groups at pre-test and post-test.Effect size(Cohen's d)was calculated to determine the differences between groups from baseline to post-test.After 12 weeks,we found that the aerobic dancing group showed significant improvement in memory(portrait memory:F=10.45,p=0.003,d=1.18).The Limit of Stability(LOS)parameters in the aerobic dancing group displayed a significant increase after the intervention(right angle:F=5.90,p=0.022,d=0.60;right-anterior angle:F=4.23,p=0.049,d=0.12).Some beneficial effects were found on flexibility,grip strength,balance and subjective well-being(sit and reach:F=0.25,p=0.62,d=−0.40;grip strength:F=3.38,p=0.08,d=0.89;one-legged standing with eyes closed:F=1.26,p=0.27,d=0.50)in the aerobic dancing group.Aerobic dancing training was effective in improving memory and balance ability in older adults during the COVID-19 pandemic in China.In the future,aerobic dancing is a promising tool to encourage physical activity in older adults.展开更多
Cholangiocarcinoma(CCA)has emerged as an intractable cancer with scanty therapeutic regimens.The aberrant activation of Yes-associated protein(YAP)and transcriptional co-activator with PDZ-binding motif(TAZ)are report...Cholangiocarcinoma(CCA)has emerged as an intractable cancer with scanty therapeutic regimens.The aberrant activation of Yes-associated protein(YAP)and transcriptional co-activator with PDZ-binding motif(TAZ)are reported to be common in CCA patients.However,the underpinning mechanism remains poorly understood.Deubiquitinase(DUB)is regarded as a main orchestrator in maintaining protein homeostasis.Here,we identified Josephin domain-containing protein 2(JOSD2)as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner.The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation in vitro and in vivo.Further analysis has highlighted the positive correlation between JOSD2 and YAP abundance in CCA patient samples.Collectively,this study uncovers the regulatory effects of JOSD2 on YAP/TAZ protein stabilities and profiles its contribution in CCA malignant progression,which may provide a potential intervention target for YAP/TAZ-related CCA patients.展开更多
Hypoxia is a common feature of solid tumors.As transcription factors,hypoxia-inducible factors(HIFs)are the master regulators of the hypoxic microenvironment;their target genes function in tumorigenesis and tumor deve...Hypoxia is a common feature of solid tumors.As transcription factors,hypoxia-inducible factors(HIFs)are the master regulators of the hypoxic microenvironment;their target genes function in tumorigenesis and tumor development.Intriguingly,both yes-associated protein(YAP)and its paralog transcriptional coactivator with a PDZ-binding motif(TAZ)play fundamental roles in the malignant progression of hypoxic tumors.As downstream effectors of the mammalian Hippo pathway,YAP and/or TAZ(YAP/TAZ)are phosphorylated and sequestered in the cytoplasm by the large tumor suppressor kinase 1/2(LATS1/2)-MOB kinase activator 1(MOB 1)complex,which restricts the transcriptional activity of YAP/TAZ.However,dephosphorylated YAP/TAZ have the ability to translocate to the nucleus where they induce transcription of target genes,most of which are closely related to cancer.Herein we review the tumor-related signaling crosstalk between YAP/TAZ and hypoxia,describe current agents and therapeutic strategies targeting the hypoxia-YAP/TAZ axis,and highlight questions that might have a potential impact in the future.展开更多
Monoclonal antibodies(m Abs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17 A can induce a rapid inflammatory response both alone and synergistic...Monoclonal antibodies(m Abs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17 A can induce a rapid inflammatory response both alone and synergistically with other proinflammatory cytokines. Accumulating evidence suggests that therapeutic intervention of IL-17 A signaling offers an attractive treatment option for autoimmune diseases and cancer. Here, we present a combinatorial approach for optimizing the affinity and thermostability of a novel anti-h IL-17 A antibody. From a large na?ve phage-displayed library, we isolated the anti-IL-17 A m Ab 7 H9 that can neutralize the effects of recombinant human IL-17 A. However, the modest neutralization potency and poor thermostability limit its therapeutic applications. In vitro affinity optimization was then used to generate 8 D3 by using yeast-displayed random mutagenesis libraries.This resulted in four key amino acid changes and provided an approximately 15-fold potency increase in a cell-based neutralization assay. Complementarity-determining regions(CDRs) of 8 D3 were further grafted onto the stable framework of the hu Fv 4 D5 to improve thermostability. The resulting hybrid antibody9 NT/S has superior stabilization and affinities beyond its original antibody. Human fibrosarcoma cellbased assays and in vivo analyses in mice indicated that the anti-IL-17 A antibody 9 NT/S efficiently inhibited the secretion of IL-17 A-induced proinflammatory cytokines. Therefore, this lead anti-IL-17 A m Ab might be used as a potential best-in-class candidate for treating IL-17 A related diseases.展开更多
Al-V-B master alloy is promising for refining Al-Si alloys,yet its optimal composition with superior efficacy remains to be explored.In this work,the evolution of refining phases in the Al-10 Si/Al-V-B system with dif...Al-V-B master alloy is promising for refining Al-Si alloys,yet its optimal composition with superior efficacy remains to be explored.In this work,the evolution of refining phases in the Al-10 Si/Al-V-B system with different V:B ratios was evaluated by thermodynamic calculations,based on which the Al-V-B refiners with V:B=1:1 and 5:1 were designed.Refining trails demonstrated that they could significantly reduce the grain size of Al-10 Si(wt.%)alloy from 1736 to 184-245μm with industrial addition amount.Detailed examinations results clarify that when V:B ratio is 1:1 the nucleation particle is(V,Al)B_(2),which has a VB_(2)-AlB_(2) core-shell structure and therefore presents the nucleation capability as AlB_(2) particle.When V:B ratio is as high as 5:1,the nucleation particle is pure VB_(2).Density functional theory(DFT)calculation indicates that(0001)VB_(2)/(111)α-Al interface has the lowest interfacial energy such that highest nucleation potency among other types of diboride/α-Al interfaces under consideration.The outcomes of this work provide fundamental guidance to develop superior V-B based refiners for Al-Si alloys.展开更多
基金supported by the Key Project of the National Natural Science Foundation of China,No.81930070(to SF)the National Natural Science Foundation of China,No.81972074(to XY)the Key Program of Natural Science Foundation of Tianjin,No.19JCZDJC34900(to XY)。
文摘Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.
基金supported by the General Program of the National Natural Science Foundation of China(NSFC,No.52075061)the Key Program of the National Natural Science Foundation of China(NSFC,No.U22B2089)the Science Fund for Distinguished Young Scholars of Chongqing(No.CSTB2022 NSCQ-JQX0006).
文摘Triboelectric nanogenerators(TENG),renowned for their remarkable capability to harness weak mechanical energy from the environment,have gained considerable attention owing to their cost-effectiveness,high output,and adaptability.This review provides a unique perspective by conducting a comprehensive and in-depth analysis of magnetically assisted TENGs that encompass structures,materials,and self-powered sensing systems.We systematically summarize the diverse functions of the magnetic assistance for TENGs,including system stiffness,components of the hybrid electromagnetic-triboelectric generator,transmission,and interaction forces.In the material domain,we review the incorporation of magnetic nano-composites materials,along with ferrofluid-based TENG and microstructure verification,which have also been summarized based on existing research.Furthermore,we delve into the research progress on physical quantity sensing and human-machine interface in magnetic-assisted TENGs.Our analysis highlights that magnetic assistance extends beyond the repulsive and suction forces under a magnetic field,thereby playing multifaceted roles in improving the output performance and environmental adaptability of the TENGs.Finally,we present the prevailing challenges and offer insights into the future trajectory of the magnetic-assisted TENGs development.
基金National Natural Science Foundation of China,No.81972074 (to XY)Natural Science Foundation of Tianjin,No.19JCZDJC34900 (to XY)National Key Research and Development Project of Stem Cell and Transformation Research,No.2019YFA0112100 (to SF)。
文摘Maintaining the integrity of the blood-spinal cord barrier is critical for the recove ry of spinal cord injury.Ferro ptosis contributes to the pathogenesis of spinal cord injury.We hypothesized that ferroptosis is involved in disruption of the blood-s pinal cord barrier.In this study,we administe red the ferroptosis inhibitor liproxstatin-1 intraperitoneally after contusive spinal co rd injury in rats.Liproxstatin-1 improved locomotor recovery and somatosensory evoked potential electrophysiological performance after spinal cord inju ry.Liproxstatin-1 maintained blood-spinal cord barrier integrity by upregulation of the expression of tight junction protein.Liproxstatin-1 inhibited ferroptosis of endothelial cell after spinal cord injury,as shown by the immunofluorescence of an endothelial cell marker(rat endothelium cell antigen-1,RECA-1) and fe rroptosis markers Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase.Liproxstatin-1reduced brain endothelial cell ferroptosis in vitro by upregulating glutathione peroxidase 4 and downregulating Acyl-CoA synthetase long-chain family member4 and 15-lipoxygenase.Furthermore,inflammatory cell recruitment and astrogliosis were mitigated after liproxstatin-1 treatment.In summary,liproxstatin-1im proved spinal cord injury recovery by inhibiting ferroptosis in endothelial cells and maintaining blood-s pinal co rd barrier integrity.
基金co-funded by the Key Project of the National Natural Science Foundation of China [grant number 42230609 and 41630425]the National Key Research and Development Plan projects [grant number 2022YFC3004101]
基金supported in part by National Key Research and Development Program of China (Grant No. 2020YFB1807001)in part by Natural Science Foundation of China (Grant No. 62171344, 62121001, 61725103, 61931005)+1 种基金in part by Young Elite Scientists Sponsorship Program by CASTin part by Key Industry Innovation Chain of Shaanxi (Grant No. 2022ZDLGY05-01, 2022ZDLGY05-06)
文摘Due to flexible deployment,unmanned aerial vehicle(UAV)mounted aerial access points are capable of expanding the coverage capabilities of existing terrestrial base stations(TBSs).Different from TBSs,however,UAV access points(UAPs)are of high mobility in horizontal and vertical dimensions,which may deteriorate the coverage performance.Worsestill,the mobility of UAPs would as well increase the pressure of wireless backhaul.In this light,we investigate the performance of the cache-enabled UAV communications network(CUCN)in terms of network spatial throughput(ST)by analyzing the line of sight(LoS)connections and non-line of sight(NLoS)connections.It is found that the network ST is exponentially decreased with the square of UAP altitude.Furthermore,contrary to intuition,a large cache size may deteriorate the network ST when UAPs are over-deployed.The reason is that a large cache size increases the hit probability,which may increase the activation of UAPs and consequently result in complicated interference.Aiming to maximize the network ST,we optimize the cache strategy under limited backhaul.Remarkably,the results show that network ST could be substantially improved by the optimized cache strategy and the performance degeneration brought by UAP high mobility could be even eliminated especially when the UAP altitude is high.
基金the financial support from the National Natural Science Foundation of China (No.21964006)the Changsha Science and Technology Planning Project (No.kq2203003)+2 种基金the Natural Science Foundation of Hunan Province (No.2020JJ4640)the Scientific Research Fund of Hunan Provincial Education Department (No.20A050)the Scientific Research Found of Changsha University (No.SF1934)。
文摘The construction and application of novel highly efficient photocatalysts have been the focus in the field of environmental pollutant removal.In this work,a novel CuFe_(2)O_(4)/Bi_(12)O_(17)Cl_(2)photocatalysts were synthesized by simple hydrothermal and chemical precipitation method.The fabricated CuFe_(2)O_(4)/Bi_(12)O_(17)Cl_(2)composite exhibited much higher photocatalytic activity than pristine CuFe_(2)O_(4)and Bi_(12)O_(17)Cl_(2)in the removal of bisphenol A(BPA)under visible-light illumination,which ascribed to the intrinsic p-n junction of CuFe_(2)O_(4)and Bi_(12)O_(17)Cl_(2).The photocatalytic degradation rate of BPA on CuFe_(2)O_(4)/Bi_(12)O_(17)Cl_(2)with an optimized CuFe_(2)O_(4)content(1.0 wt.%)reached 93.0%within 30 min.The capture experiments of active species confirmed that the hydroxyl radicals(·OH)and superoxide radicals(·O_(2)^(-))played crucial roles in photocatalytic BPA degradation process.Furthermore,the possible degradation mechanism and pathways of BPA was proposed according to the detected intermediates in photocatalytic reaction process.
基金supported by the National Natural Science Foundation of China(Nos.22074013 and 22073030)The CPU time was supported by the Supercomputer Centre of East China Normal University(ECNU Public Platform for Innovation No.001).
文摘Chiral chemicals have attracted significant interest in the pharmaceutical industry,yet the separation methods to get pure enantiomers from racemic mixture are still challenging.To date,the separation of enantiomers still mainly depends on chromatography using high-cost chiral stationary phases.Herein,wood channels were used as the handheld integrated device,and enantiomer separation was simultaneously detected using an electrochemical detector.In this method,a chiral UIO-66(L-UIO-66)modified enantiomer separation zone and carbonized wood based online detection zone are integrated along a single wood column.Based on the in situ separation results from the chronoamperometry data,the wood device shows excellent separation ability for a wide range of electrochemically active enantiomers,including 3,4-dihydroxyphenylalanine,amino acids,ascorbic acid,carnitine,and penicillamine with high chirality purity.The unbiased molecular dynamic simulations indicate that the excellent chiral recognition and separation are attributed to the different barriers from the bound states to the dissociated state of the enantiomers in the homochiral microenvironment of the framework.This integrated enantiomer separation-electrochemical detection device provides a novel,easy,and low-cost platform for the separation of pure enantiomer from racemic mixture.
基金supported by the National Key Research and Development Project of Stem Cell and Transformation Research(2019YFA0112100)Tianjin Key Medical Discipline(Specialty)Construct Project(TJYXZDXK-027A)International Innovation Summit for Academicians and Experts(22JRRCRC00010).We thank the Large Instrument Sharing Platform of Tianjin Medical University for the availability of the instruments.
文摘Spinal cord injury(SCI)is a traumatic condition that results in impaired motor and sensory function.Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord,and ferroptosis inhibitors are effective in reducing inflammation and repairing SCI.Although human umbilical cord mesenchymal stem cells(Huc-MSCs)can ameliorate inflammatory microenvironments and promote neural regeneration in SCI,their efficacy is greatly limited by the local microenvironment after SCI.Therefore,in this study,we constructed a drug-release nanoparticle system with synergistic Huc-MSCs and ferroptosis inhibitor,in which we anchored Huc-MSCs by a Tz-A6 peptide based on the CD44-targeting sequence,and combined with the reactive oxygen species(ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at the other end for SCI repair.Meanwhile,we also modified the classic ferroptosis inhibitor Ferrostatin-1(Fer-1)and synthesized a new prodrug Feborastatin-1(Feb-1).The results showed that this treatment regimen significantly inhibited the ferroptosis and inflammatory response after SCI,and promoted the recovery of neurological function in rats with SCI.This study developed a combination therapy for the treatment of SCI and also provides a new strategy for the construction of a drug-coordinated cell therapy system.
基金supported by Science Program of Beijing City[grant number Z221100007922019]the High Level Public Health Technical Talent Training Plan[grant number xuekegugan-01-019]National Key Research and Development Project of China[grant number 2023YFC0872400]。
文摘In response to problems of poor sampling quality,low sensitivity,and high demand for medical personnel regarding the current severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)oropharyngeal(OP)swab sampling used in China,we aimed to evaluate the diagnostic performance and acceptability of saliva-based nucleic acid amplification tests(NAATs)in China.The results showed that,using nasopharyngeal(NP)swab results as the gold standard,the overall sensitivities for saliva specimens and OP swabs were 93.3%and 85.0%,the specificities were 92.6%and 93.8%,respectively.The results of an acceptability survey showed that the scores for saliva,OP,and NP samples were 9.46±1.69,8.11±2.42,and 4.58±3.82 out of 10,respectively,with significant differences among the three groups(P<0.05).With higher sensitivity,comparable specificity,and strong public preference,saliva-based NAATs represent a convenient and effective method for detecting SARS-CoV-2 in future epidemics.
基金supported by the State Key Program of the Natural Science Foundation of China(81830107)the Natural Science Foundation of China(81973349,82304517)+2 种基金the Key R&D Program of Zhejiang(2022C03077)the Fundamental Research Funds for the Central Universities(226-2023-00059)the China Postdoctoral Science Foundation(2023M733130)。
文摘Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths worldwide.Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable for and beneficial to a mere~30%of NSCLC patients.Consequently,the need for novel strategies addressing NSCLC remains pressing.Deubiquitinases(DUBs),a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic targets.Nevertheless,the mechanisms by which DUBs promote NSCLC remain poorly understood.Through a global analysis of the 97 DUBs’contribution to NSCLC survival possibilities using The Cancer Genome Atlas(TCGA)database,we found that high expression of Josephin Domain-containing protein 2(JOSD2)predicted the poor prognosis of patients.Depletion of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in vivo.Mechanically,we found that JOSD2 restricts the kinase activity of LKB1,an important tumor suppressor generally inactivated in NSCLC,by removing K6-linked polyubiquitination,an action vital for maintaining the integrity of the LKB1-STRAD-MO25 complex.Notably,we identified the first small-molecule inhibitor of JOSD2,and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in vivo.Our findings highlight the vital role of JOSD2 in hindering LKB1 activity,underscoring the therapeutic potential of targeting JOSD2 in NSCLC,especially in those with inactivated LKB1,and presenting its inhibitors as a promising strategy for NSCLC treatment.
基金The authors gratefully acknowledge financial support from the National Natural Science Foundation of China(Nos.61935016,92056119,22175118,62288102,62274135)National Key Research and Development Program of China(under Grants No.2021YFA0715502)+2 种基金Double First-Class Initiative Fund of ShanghaiTech University,and the Science and Technology Commission of Shanghai Municipality(Nos.20XD1402500 and 20JC1415800)Bertil och Britt Svenssons Stiftelse and Swedish Energy Agency(P2022-00394)The authors appreciate the Instrument Analysis Center and Centre for High-resolution Electron Microscopy(CħEM)and the high-performance computing(HPC)Platform of ShanghaiTech University.The authors gratefully thank professor John A.McGuire for the helpful discussion.
文摘Regulation of perovskite growth plays a critical role in the development of high-performance optoelectronic devices.However,judicious control of the grain growth for perovskite light emitting diodes is elusive due to its multiple requirements in terms of morphology,composition,and defect.Herein,we demonstrate a supramolecular dynamic coordination strategy to regulate perovskite crystallization.The combined use of crown ether and sodium trifluoroacetate can coordinate with A site and B site cations in ABX_(3) perovskite,respectively.The formation of supramolecular structure retard perovskite nucleation,while the transformation of supramolecular intermediate structure enables the release of components for slow perovskite growth.This judicious control enables a segmented growth,inducing the growth of insular nanocrystal consist of low-dimensional structure.Light emitting diode based on this perovskite film eventually brings a peak external quantum efficiency up to 23.9%,ranking among the highest efficiency achieved.The homogeneous nano-island structure also enables high-efficiency large area(1 cm^(2))device up to 21.6%,and a record high value of 13.6%for highly semi-transparent ones.
基金supported by the National Natural Science Foundation of China (No. 21964006)the Hunan Provincial Natural Science Foundation of China (No. 2020JJ4640)+1 种基金the Scientific Research Fund of Hunan Provincial Education Department (No. 20A050)the Scientific Research Found of Changsha University (No. SF1934)
文摘In this work,a novel dual Z-scheme Bi_(2)WO_(6)/g-C_(3)N_(4)/black phosphorus quantum dots(Bi_(2)WO_(6)/g-C_(3)N_(4)/BPQDs)composites were fabricated and utilized towards photocatalytic degradation of bisphenol A(BPA)under visible-light irradiation.Optimizing the content of g-C_(3)N_(4) and BPQDs in Bi_(2)WO_(6)/g-C_(3)N_(4)/BPQDs composites to a suitable mass ratio can enhance the visible-light harvesting capacity and increase the charge separation efficiency and the transfer rate of excited-state electrons and holes,resulting in much higher photocatalytic activity for BPA degradation(95.6%,at 20 mg/L in 120 min)than that of Bi2WO6(63.7%),g-C_(3)N_(4)(25.0%),BPQDs(8.5%),and Bi_(2)WO_(6)/g-C_(3)N_(4)(79.6%),respectively.Radical trapping experiments indicated that photogenerated holes(h+)and superoxide radicals(•O_(2)−)played crucial roles in photocatalytic BPA degradation.Further,the possible degradation pathway and photocatalytic mechanism was proposed by analyzing the BPA intermediates.Thiswork also demonstrated that the Bi2WO6/g-C_(3)N_(4)/BPQDs as effective photocatalystswas stable and have promising potential to remove environmental contaminants from real water samples.
基金This study was supported by the MOE(Ministry of Education in China)Project of Humanities and Social Sciences(20YJC890053)Shaanxi Province Social Science Foundation Program(2020Q009).
文摘During the Coronavirus disease(COVID-19),the physical activity of older adults is at a lower level.The study aimed to examine the effectiveness of aerobic dancing on physical fitness and cognitive function in older adults.We conducted a randomized controlled trial with 34 older adults who were assigned into an aerobic dancing group and a control group.Three dance sessions weekly for 60min were scheduled for the aerobic dancing group for a total of 12 weeks.Physical fitness,blood pressure,lipids,glucose,cognitive function were assessed before and after the intervention.Baseline adjusted Analysis of Covariance(ANCOVA)was used to determine whether outcome variables varied between groups at pre-test and post-test.Effect size(Cohen's d)was calculated to determine the differences between groups from baseline to post-test.After 12 weeks,we found that the aerobic dancing group showed significant improvement in memory(portrait memory:F=10.45,p=0.003,d=1.18).The Limit of Stability(LOS)parameters in the aerobic dancing group displayed a significant increase after the intervention(right angle:F=5.90,p=0.022,d=0.60;right-anterior angle:F=4.23,p=0.049,d=0.12).Some beneficial effects were found on flexibility,grip strength,balance and subjective well-being(sit and reach:F=0.25,p=0.62,d=−0.40;grip strength:F=3.38,p=0.08,d=0.89;one-legged standing with eyes closed:F=1.26,p=0.27,d=0.50)in the aerobic dancing group.Aerobic dancing training was effective in improving memory and balance ability in older adults during the COVID-19 pandemic in China.In the future,aerobic dancing is a promising tool to encourage physical activity in older adults.
基金supported by the Key Program of the Natural Science Foundation of China(No.81830107)the Natural Science Foundation for Distinguished Young Scholar of China(No.81625024)+1 种基金the Natural Science Foundation of China(No.81773753,No.81973349)the Zhejiang Provincial Natural Science Foundation(No.LR19H310002 and No.LR21H300003,China)。
文摘Cholangiocarcinoma(CCA)has emerged as an intractable cancer with scanty therapeutic regimens.The aberrant activation of Yes-associated protein(YAP)and transcriptional co-activator with PDZ-binding motif(TAZ)are reported to be common in CCA patients.However,the underpinning mechanism remains poorly understood.Deubiquitinase(DUB)is regarded as a main orchestrator in maintaining protein homeostasis.Here,we identified Josephin domain-containing protein 2(JOSD2)as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner.The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation in vitro and in vivo.Further analysis has highlighted the positive correlation between JOSD2 and YAP abundance in CCA patient samples.Collectively,this study uncovers the regulatory effects of JOSD2 on YAP/TAZ protein stabilities and profiles its contribution in CCA malignant progression,which may provide a potential intervention target for YAP/TAZ-related CCA patients.
基金supported by National Natural Science Foundation of China(81625024 and 81773753)to Bo YangZhejiang Provincial Natural Science Foundation(LR19H310002 and LY16H310004,China)to Hong Zhu and Xiaoyang Dai,respectively
文摘Hypoxia is a common feature of solid tumors.As transcription factors,hypoxia-inducible factors(HIFs)are the master regulators of the hypoxic microenvironment;their target genes function in tumorigenesis and tumor development.Intriguingly,both yes-associated protein(YAP)and its paralog transcriptional coactivator with a PDZ-binding motif(TAZ)play fundamental roles in the malignant progression of hypoxic tumors.As downstream effectors of the mammalian Hippo pathway,YAP and/or TAZ(YAP/TAZ)are phosphorylated and sequestered in the cytoplasm by the large tumor suppressor kinase 1/2(LATS1/2)-MOB kinase activator 1(MOB 1)complex,which restricts the transcriptional activity of YAP/TAZ.However,dephosphorylated YAP/TAZ have the ability to translocate to the nucleus where they induce transcription of target genes,most of which are closely related to cancer.Herein we review the tumor-related signaling crosstalk between YAP/TAZ and hypoxia,describe current agents and therapeutic strategies targeting the hypoxia-YAP/TAZ axis,and highlight questions that might have a potential impact in the future.
基金supported by National Key R&D Program of China under Grant 2017YFA0205400National Natural Science Foundation of China under Grant 81874316,81773781 and81530093+2 种基金National Drug Innovation Major Project of China under Grant 2018ZX09711001-003-001Chinese Academy of Medical Sciences(CAMS,Beijing,China)Central Publicinterest Scientific Institution Basal Research Fund under 2017PT31046 and 2018RC350004CAMS Innovation Found for Medical Sciences(2016-I2M-3-008 and 2016-I2M-1-007)
文摘Monoclonal antibodies(m Abs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17 A can induce a rapid inflammatory response both alone and synergistically with other proinflammatory cytokines. Accumulating evidence suggests that therapeutic intervention of IL-17 A signaling offers an attractive treatment option for autoimmune diseases and cancer. Here, we present a combinatorial approach for optimizing the affinity and thermostability of a novel anti-h IL-17 A antibody. From a large na?ve phage-displayed library, we isolated the anti-IL-17 A m Ab 7 H9 that can neutralize the effects of recombinant human IL-17 A. However, the modest neutralization potency and poor thermostability limit its therapeutic applications. In vitro affinity optimization was then used to generate 8 D3 by using yeast-displayed random mutagenesis libraries.This resulted in four key amino acid changes and provided an approximately 15-fold potency increase in a cell-based neutralization assay. Complementarity-determining regions(CDRs) of 8 D3 were further grafted onto the stable framework of the hu Fv 4 D5 to improve thermostability. The resulting hybrid antibody9 NT/S has superior stabilization and affinities beyond its original antibody. Human fibrosarcoma cellbased assays and in vivo analyses in mice indicated that the anti-IL-17 A antibody 9 NT/S efficiently inhibited the secretion of IL-17 A-induced proinflammatory cytokines. Therefore, this lead anti-IL-17 A m Ab might be used as a potential best-in-class candidate for treating IL-17 A related diseases.
基金financially supported by the National Natural Science Foundation of China(No.51871138)the Science and Technology Commission of Shanghai Municipality(No.19010500400)the"111"projects(No.D16002)。
文摘Al-V-B master alloy is promising for refining Al-Si alloys,yet its optimal composition with superior efficacy remains to be explored.In this work,the evolution of refining phases in the Al-10 Si/Al-V-B system with different V:B ratios was evaluated by thermodynamic calculations,based on which the Al-V-B refiners with V:B=1:1 and 5:1 were designed.Refining trails demonstrated that they could significantly reduce the grain size of Al-10 Si(wt.%)alloy from 1736 to 184-245μm with industrial addition amount.Detailed examinations results clarify that when V:B ratio is 1:1 the nucleation particle is(V,Al)B_(2),which has a VB_(2)-AlB_(2) core-shell structure and therefore presents the nucleation capability as AlB_(2) particle.When V:B ratio is as high as 5:1,the nucleation particle is pure VB_(2).Density functional theory(DFT)calculation indicates that(0001)VB_(2)/(111)α-Al interface has the lowest interfacial energy such that highest nucleation potency among other types of diboride/α-Al interfaces under consideration.The outcomes of this work provide fundamental guidance to develop superior V-B based refiners for Al-Si alloys.
