The NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome is an intracellular protein complex containing a nucleotide-binding oligomerization domain,leucine-rich repeats,and a pyrin domain.It i...The NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome is an intracellular protein complex containing a nucleotide-binding oligomerization domain,leucine-rich repeats,and a pyrin domain.It is a key regulator of inflammation in viral pneumonia(VP).Small-molecule inhibitors targeting various NLRP3 binding sites are advancing into early clinical trials,but their therapeutic utility is incompletely established.Xuanfei Baidu Formula(XF),clinically used for VP treatment,attenuates NLRP3 activation by hampering caspase-11 to impede polarization of pro-inflammatory macrophages in a model of lipopolysaccharide(LPS)-induced lung injury inmice.Herein,we demonstrate that XF attenuated influenza A virus(IAV)-induced lung inflammation as well as lung injury in immunocompetent(but not in macrophage-depleted)mice.RNA sequencing of sorted lung macrophages from IAV-infected mice revealed that XF inhibited activation of the NLRP3 inflammation and interleukin(IL)-1βproduction.Quantitative nuclear magnetic resonance of XF enabled us to develop XF-Comb1,a fixed-ratio combination of five bioactive compounds that recapitulated the bioactivity of XF in suppressing NLRP3 activation in macrophages in vitro and in vivo.Interestingly,XF-Comb1 inhibited assembly of the NLRP3 inflammasome through multi-site interactions with functional residues of NLRP3,apoptosis-associated speck-like protein containing caspase recruitment domain(ASC),and caspase-1.Taken together,this work advances the development of NLRP3 inhibitors by translating a complex herbal formula into defined bioactive compounds.展开更多
Perfluoroalkyl and polyfluoroalkyl substances(PFASs)pollution with their toxicity,carcinogenicity,and persistence has been concerned worldwide.Research into novel materials for detecting and removing PFASs has increas...Perfluoroalkyl and polyfluoroalkyl substances(PFASs)pollution with their toxicity,carcinogenicity,and persistence has been concerned worldwide.Research into novel materials for detecting and removing PFASs has increased rapidly,particularly in regard to the emergence of well-characterized single-atom materials(SAMs).Owing to the high selectivity,high atom utilization,and abundant active sites of SAMs,these materials exhibit remarkable efficacy in the detection and removal of PFASs.In this work,recent advances in the synthesis of SAMs for the detection and removal PFASs are reviewed.In-depth discussions of the structure-activity relationship and reaction mechanisms have demonstrated the high efficiency,activity,and selectivity of SAMs for the detection,adsorption,and degradation of PFASs.To optimize the application of SAMs in PFASs remediation,this review comprehensively surveys SAMs applications for PFASs and analyzes potential design strategies based on synthesis methods and corresponding properties.Synthesis strategies such as wet-chemistry,which offer ease of operation and high potential for large-scale production,are recommended for the further exploration of specific SAMs for the detection and removal of PFASs.Finally,this review identifies the challenges and opportunities for development of SAMs for the detection and remediation of PFASs,providing an outlook on strategic goals for a green economy and sustainable development.展开更多
Sequential processing(SqP)of the active layer offers independent optimization of the donor and acceptor with more targeted solvent design,which is considered the most promising strategy for achieving efficient organic...Sequential processing(SqP)of the active layer offers independent optimization of the donor and acceptor with more targeted solvent design,which is considered the most promising strategy for achieving efficient organic solar cells(OSCs).In the SqP method,the favorable interpenetrating network seriously depends on the fine control of the bottom layer swelling.However,the choice of solvent(s)for both the donor and acceptor have been mostly based on a trial-and-error manner.A single solvent often cannot achieve sufficient yet not excessive swelling,which has long been a difficulty in the high efficient SqP OSCs.Herein,two new isomeric molecules are introduced to fine-tune the nucleation and crystallization dynamics that allows judicious control over the swelling of the bottom layer.The strong non-covalent interaction between the isomeric molecule and active materials provides an excellent driving force for optimize the swelling-process.Among them,the molecule with high dipole moment promotes earlier nucleation of the PM6 and provides extended time for crystallization during SqP,improving bulk morphology and vertical phase segregation.As a result,champion efficiencies of 17.38%and 20.00%(certified 19.70%)are achieved based on PM6/PYF-T-o(all-polymer)and PM6/BTP-eC9 devices casted by toluene solvent.展开更多
Secondary iron-sulfate minerals such as jarosite,which are easily formed in acid mine drainage,play an important role in controlling metal mobility.In this work,the typical iron-oxidizing bacterium Acidithiobacillus f...Secondary iron-sulfate minerals such as jarosite,which are easily formed in acid mine drainage,play an important role in controlling metal mobility.In this work,the typical iron-oxidizing bacterium Acidithiobacillus ferrooxidans ATCC 23270 was selected to synthesize jarosite in the presence of antimony ions,during which the solution behavior,synthetic product composition,and bacterial metabolism were studied.The results show that in the presence of Sb(V),Fe^(2+)was rapidly oxidized to Fe^(3+)by A.ferrooxidans and Sb(V)had no obvious effect on the biooxidation of Fe^(2+)under the current experimental conditions.The presence of Sb(Ⅲ)inhibited bacterial growth and Fe^(2+)oxidation.For the group with Sb(Ⅲ),products with amorphous phaseswere formed 72 hr later,whichwere mainly ferrous sulfate and pentavalent antimony oxide,and the amorphous precursor was finally transformed into a more stable crystal phase.For the group with Sb(V),the morphology and structure of jarosite were changed in comparison with those without Sb.The biomineralization process was accompanied by the removal of 94%Sb(V)to form jarosite containing the Fe-Sb-O complex.Comparative transcriptome analysis shows differential effects of Sb(Ⅲ)and Sb(V)on bacterial metabolism.The expression levels of functional genes related to cell components were much more downregulated for the group with Sb(Ⅲ)butmuch more regulated for that with Sb(V).Notably,cytochrome c and nitrogen fixation-relevant genes for the A.f_Fe^(2+)_Sb(Ⅲ)group were enhanced significantly,indicating their role in Sb(Ⅲ)resistance.This study is of great value for the development of antimony pollution control and remediation technology.展开更多
Biodegradable magnesium alloys show promising potential for pancreatic duct stents,yet their degradation varies significantly across physiological environments.This study compared the corrosion rates of extruded Mg-2Z...Biodegradable magnesium alloys show promising potential for pancreatic duct stents,yet their degradation varies significantly across physiological environments.This study compared the corrosion rates of extruded Mg-2Zn-xMn(x=0,0.5,1.0,1.5 wt.%)alloys in human pancreatic fluid.The results revealed that the alloys undergo different corrosion mechanisms in human pancreatic fluid,emphasizing the necessity of conducting evaluations under physiologically relevant conditions.Further investigations into the degradation mechanism in pancreatic fluid indicated that the alkaline PH(8.3–8.7),high bicarbonate concentration,and enzymatic activity significantly influence the corrosion process.Electrochemical and immersion tests showed rapid initial corrosion due to Cl^(−)attack,followed by the formation of a protective Mg(OH)_(2),MgCO_(3),and Ca_(3)(PO_(4))_(2)layer that slowed degradation.However,digestive enzymes,particularly trypsin,disrupt passivation by interacting with organic components,leading to pitting and filiform corrosion.Among the investigated alloys,Mg-2Zn-1.0Mn exhibited the most favorable combination of corrosion resistance,mechanical performance,and cytocompatibility.This study highlights the critical impact of pancreatic fluid on magnesium alloy degradation and stresses the need for physiologically accurate evaluations.展开更多
Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a...Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.展开更多
Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotect...Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells(bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N_2/5% CO_2 for 6 hours, followed by high-glucose medium containing 95% O_2 and 5% CO_2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations(diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1β, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1β, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway.展开更多
Single-atom catalysts(SACs)have garnered significant attention in lithium-sulfur(Li-S)batteries for their potential to mitigate the severe polysulfide shuttle effect and sluggish redox kinetics.However,the development...Single-atom catalysts(SACs)have garnered significant attention in lithium-sulfur(Li-S)batteries for their potential to mitigate the severe polysulfide shuttle effect and sluggish redox kinetics.However,the development of highly efficient SACs and a comprehensive understanding of their structure-activity relationships remain enormously challenging.Herein,a novel kind of Fe-based SAC featuring an asymmetric FeN_(5)-TeN_(4) coordination structure was precisely designed by introducing Te atom adjacent to the Fe active center to enhance the catalytic activity.Theoretical calculations reveal that the neighboring Te atom modulates the local coordination environment of the central Fe site,elevating the d-band center closer to the Fermi level and strengthening the d-p orbital hybridization between the catalyst and sulfur species,thereby immobilizing polysulfides and improving the bidirectional catalysis of Li-S redox.Consequently,the Fe-Te atom pair catalyst endows Li-S batteries with exceptional rate performance,achieving a high specific capacity of 735 mAh g^(−1) at 5 C,and remarkable cycling stability with a low decay rate of 0.038%per cycle over 1000 cycles at 1 C.This work provides fundamental insights into the electronic structure modulation of SACs and establishes a clear correlation between precisely engineered atomic configurations and their enhanced catalytic performance in Li-S electrochemistry.展开更多
Background Heart failure(HF)is a leading cause of hospitalization and mortality for older chronic kidney disease(CKD)patients.However,the epidemiological data is scarce.We aimed to determine the prevalence of left ven...Background Heart failure(HF)is a leading cause of hospitalization and mortality for older chronic kidney disease(CKD)patients.However,the epidemiological data is scarce.We aimed to determine the prevalence of left ventricular(LV)dysfunction and HF,and to explore the risk factors for HF among those patients.Methods This is a cross-sectional analysis of the China Hypertension Survey conducted between October 2012 and December 2015.A total of 5,808 participants aged≥65 years were included in the analysis.Self-reported history of HF and any other cardiovascular diseases was acquired.2-D and Doppler echocardiography were used to assess LV dysfunction.CKD was defined as either estimated glomerular filtration rate(eGFR)<60 mL/min per 1.73 m2 or urinary albumin to creatinine ratio(ACR)≥30 mg/g.Results Among CKD patients aged≥65 years,the weighted prevalence of HF,heart failure with preserved ejection fraction(HFpEF),heart failure with mid-range ejection fraction(HFmrEF),and heart failure with reduced ejection fraction(HFrEF)was 4.8%,2.5%,0.8%,and 1.7%,respectively.The weighted prevalence of HF was 5.0%in patients with eGFR<60 mL/min per 1.73 m2,and was 5.9%in patients with ACR≥30 mg/g.The prevalence of LV systolic dysfunction was 3.1%,and while it was 8.9%for moderate/severe diastolic dysfunction.Multivariate analysis showed that smoking was significantly associated with the risk of HF.Furthermore,age,smoking,and residents in rural areas were significantly associated with a risk of LV diastolic dysfunction.Conclusions The prevalence of HF and LV dysfunction was high in older patients with CKD,suggesting that particular strategies will be required.展开更多
BACKGROUND Reports on bacterial infection(BI)in decompensated cirrhosis(DC)is mainly from alcoholic cirrhosis.The role of BI as a trigger or complication of acute-onchronic liver failure(ACLF)in patients with hepatiti...BACKGROUND Reports on bacterial infection(BI)in decompensated cirrhosis(DC)is mainly from alcoholic cirrhosis.The role of BI as a trigger or complication of acute-onchronic liver failure(ACLF)in patients with hepatitis B virus decompensated cirrhosis(HBV-DC)remains to be investigated.AIM To investigate the impact of BI on the outcomes of the patients with HBV-DC admitted into the hospital with or without ACLF.METHODS This retrospective study included patients with HBV-DC admitted to two tertiary centers in China.In-hospital overall survival,90-d transplant-free survival,5-year post-discharge survival,and cumulative incidence of ACLF were evaluated.Risk factors for death were analyzed considering liver transplantation as a competing event.RESULTS A total of 1281 hospitalized HBV-DC patients were included;284 had ACLF at admission.The overall prevalence of BI was 28.1%.The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without,in both the patients admitted with and without ACLF.The presence of BI significantly increased the risk of developing ACLF[subdistribution hazard ratio(sHR)=2.52,95%CI:1.75-3.61,P<0.001]in the patients without ACLF.In the patients discharged alive,those who had an episode of BI had a significantly lower 5-year transplant-free survival.BI was an independent risk factor for death in the patients admitted without ACLF(sHR=3.28,95%CI:1.93-5.57),while in ACLF admissions,the presence of pneumonia,but not other type of BI,independently increased the risk of death(sHR=1.87,95%CI:1.24-2.82).CONCLUSION BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival.HBV-DC patients should be monitored carefully for the development of BI,especially pneumonia,to avoid an adverse outcome.展开更多
Objective:Hepatocellular carcinoma(HCC)is a lethal global disease that requires an accurate diagnosis.We assessed the potential of 5 serum biomarkers(AFP,AFU,GGT-II,GPC3,and HGF)in the diagnosis of HCC.Methods:In this...Objective:Hepatocellular carcinoma(HCC)is a lethal global disease that requires an accurate diagnosis.We assessed the potential of 5 serum biomarkers(AFP,AFU,GGT-II,GPC3,and HGF)in the diagnosis of HCC.Methods:In this retrospective study,we measured the serum levels of each biomarker using ELISAs in 921 participants,including 298 patients with HCC,154 patients with chronic hepatitis(CH),122 patients with liver cirrhosis(LC),and 347 healthy controls from 3 hospitals.Patients negative for hepatitis B surface antigen and hepatitis C antibody(called"NBNC-HCC")and patients positive for the above indices(called"HBV-HCC and HCV-HCC")were enrolled.The selected diagnostic model was constructed using a training cohort(n=468),and a validation cohort(n=453)was used to validate our results.Receiver operating characteristic analysis was used to evaluate the diagnostic accuracy.Results:Theα-L-fucosidase(AFU)/α-fetoprotein(AFP)combination was best able to distinguish NBNC-HCC[area under the curve:0.986(95%confidence interval:0.958–0.997),sensitivity:92.6%,specificity:98.9%]from healthy controls in the test cohort.For screening populations at risk of developing HCC(CH and LC),the AFP/AFU combination improved the diagnostic specificity for early-stage HCC[area under the curve:0.776(0.712–0.831),sensitivity:52.5%,specificity:91.6%in the test group].In all-stage HBV-HCC and HCV-HCC,AFU was also the best candidate biomarker combined with AFP[area under the curve:0.835(0.784–0.877),sensitivity 69.1%,specificity:87.4%in the test group].All results were verified in the validation group.Conclusions:The AFP/AFU combination could be used to identify NBNC-HCC from healthy controls and hepatitis-related HCC from at-risk patients.展开更多
The influence of squeeze casting pressure on nanoparticle distribution and mechanical properties of 2 wt.%nano-SiC_(p)/Al−Cu composites assisted with ultrasonic vibration was investigated.Results show that as the appl...The influence of squeeze casting pressure on nanoparticle distribution and mechanical properties of 2 wt.%nano-SiC_(p)/Al−Cu composites assisted with ultrasonic vibration was investigated.Results show that as the applied pressure increases from 0 to 400 MPa,theα(Al)grains are significantly refined at first and then the refinement trend slows down,and the porosity of composites is gradually reduced.When the applied pressure is 400 MPa,α(Al)grain size is reduced from 105 to 25μm,and the nanoparticle distribution is significantly improved,resulting in the optimal mechanical properties of the composites.The ultimate tensile strength,yield strength and elongation of the composites are 290 MPa,182 MPa and 10%,which are 52.6%,25.5%and 400%higher than those of the nano-SiC_(p)/Al−Cu composites prepared by gravity casting(0 MPa).The enhancement in strength and elongation of nano-SiC_(p)/Al−Cu composites under high pressure is mainly attributed to grain refinement,reduction of porosity and uniform distribution of nanoparticles.展开更多
Sanduao is an important sea-breeding bay in Fujian,South China and holds a high economic status in aquaculture.Quickly and accurately obtaining information including the distribution area,quantity,and aquaculture area...Sanduao is an important sea-breeding bay in Fujian,South China and holds a high economic status in aquaculture.Quickly and accurately obtaining information including the distribution area,quantity,and aquaculture area is important for breeding area planning,production value estimation,ecological survey,and storm surge prevention.However,as the aquaculture area expands,the seawater background becomes increasingly complex and spectral characteristics differ dramatically,making it difficult to determine the aquaculture area.In this study,we used a high-resolution remote-sensing satellite GF-2 image to introduce a deep-learning Richer Convolutional Features(RCF)network model to extract the aquaculture area.Then we used the density of aquaculture as an assessment index to assess the vulnerability of aquaculture areas in Sanduao.The results demonstrate that this method does not require land and water separation of the area in advance,and good extraction can be achieved in the areas with more sediment and waves,with an extraction accuracy>93%,which is suitable for large-scale aquaculture area extraction.Vulnerability assessment results indicate that the density of aquaculture in the eastern part of Sanduao is considerably high,reaching a higher vulnerability level than other parts.展开更多
Aluminum oxide inclusions in SWRS82B steel seriously affect the drawing performance of steel strands.The effects of different addition amounts of yttrium(within the range of 0%–0.026%)on the composition,morphology,si...Aluminum oxide inclusions in SWRS82B steel seriously affect the drawing performance of steel strands.The effects of different addition amounts of yttrium(within the range of 0%–0.026%)on the composition,morphology,size and spacing of aluminum oxide inclusions were studied by scanning electron microscopy and energy spectrum analysis.Based on classical thermodynamics and FactSage software,the predominance diagram of inclusions in Fe–O–S–Y system and the effect of the addition of rare earth yttrium on the stability of alumina inclusions were calculated.The results showed that molten steel was modified by adding the rare earth element yttrium.It can be inferred that the approximate route of target inclusion modification was:Al_(2)O_(3)→Y_(2)S_(3)+YAlO_(3)+Al_(2)O_(3)→Y_(2)S_(3)+YAlO_(3)+Y_(2)O_(2)S+YAlO_(3)+Al_(2)O_(3)→Y_(2)S_(3)+Y_(2)O_(2)S.The experimental samples with 0.026%added yttrium had the best inclusion characteristics,in which the inclusion surface density distribution was uniform,and the interfacial distance between inclusions was mainly in the range of 100–500μm.After modification,the average inclusion size in molten steel was reduced by 6.9–8.6μm.The mechanism of yttrium modification was discussed based on actual calculation results and experimental results.展开更多
BACKGROUND Bevacizumab and sintilimab combined interventional treatment(BeSiIT)and L envatinib and sintilimab combined interventional treatment(LeSiIT)are two commonly used therapeutic regimens for intermediate-advanc...BACKGROUND Bevacizumab and sintilimab combined interventional treatment(BeSiIT)and L envatinib and sintilimab combined interventional treatment(LeSiIT)are two commonly used therapeutic regimens for intermediate-advanced hepatocellular carcinoma(HCC)in clinical practice.AIM To compare the clinical efficacy and safety of BeSiIT and LeSiIT for the treatment of intermediate and advanced HCC.METHODS Patients diagnosed with intermediate-advanced HCC and initially treated with BeSiIT or LeSiIT in the Tianjin Medical University Cancer Institute and Hospital between February 2020 and July 2021 were included.The primary endpoint was progression-free survival(PFS),and the secondary endpoints were overall survival(OS),objective response rate(ORR),disease control rate(DCR),conversion rate,and treatmentrelated adverse events.RESULTS Total 127 patients met the inclusion criteria and were divided into BeSiIT and LeSiIT groups.Twenty-eight and fifty patients in the BeSiIT and LeSiIT groups,respectively,were assessed after 1:2 propensity score matching.PFS and OS rates were not significantly different between the two groups.No significant variations were noted in ORRs or DCRs according to the Response Evaluation Criteria in Solid Tumors(RECIST),and modified RECIST.BeSiIT group showed a better conversion rate than the LeSiIT group(P=0.043).Both groups showed manageable toxicity profiles.Multivariate analysis showed that the independent factors associated with PFS were alphafetoprotein levels and carcinoembryonic antigen score.CONCLUSION In intermediate-to-advanced HCC,the BeSiIT and LeSiIT groups exhibited acceptable toxicities and comparable PFS,OS,and ORR.展开更多
Magnolia biondii Pamp.(Magnoliaceae,magnoliids)is a phylogenetically,economically,and medicinally important ornamental tree species widely grown and cultivated in the north-temperate regions of China.Determining the g...Magnolia biondii Pamp.(Magnoliaceae,magnoliids)is a phylogenetically,economically,and medicinally important ornamental tree species widely grown and cultivated in the north-temperate regions of China.Determining the genome sequence of M.biondii would help resolve the phylogenetic uncertainty of magnoliids and improve the understanding of individual trait evolution within the Magnolia genus.We assembled a chromosome-level reference genome of M.biondii using~67,~175,and~154Gb of raw DNA sequences generated via Pacific Biosciences single-molecule real-time sequencing,10X Genomics Chromium,and Hi-C scaffolding strategies,respectively.The final genome assembly was~2.22Gb,with a contig N50 value of 269.11 kb and a BUSCO complete gene percentage of 91.90%.Approximately 89.17%of the genome was organized into 19 chromosomes,resulting in a scaffold N50 of 92.86Mb.The genome contained 47,547 protein-coding genes,accounting for 23.47%of the genome length,whereas 66.48%of the genome length consisted of repetitive elements.We confirmed a WGD event that occurred very close to the time of the split between the Magnoliales and Laurales.Functional enrichment of the Magnolia-specific and expanded gene families highlighted genes involved in the biosynthesis of secondary metabolites,plant–pathogen interactions,and responses to stimuli,which may improve the ecological fitness and biological adaptability of the lineage.Phylogenomic analyses revealed a sister relationship of magnoliids and Chloranthaceae,which are sister to a clade comprising monocots and eudicots.The genome sequence of M.biondii could lead to trait improvement,germplasm conservation,and evolutionary studies on the rapid radiation of early angiosperms.展开更多
Gambogic acid(GA)is a potential clinical anticancer drug that can exert antitumor effects via various molecular mechanisms.Notwithstanding,GA’s low water solubility,poor stability,short half-life,and unavoidable toxi...Gambogic acid(GA)is a potential clinical anticancer drug that can exert antitumor effects via various molecular mechanisms.Notwithstanding,GA’s low water solubility,poor stability,short half-life,and unavoidable toxic side effects have significantly hampered its clinical application.Erythrocyte membranecoated nanoparticles(RBCM-NPs)improve drug’s physicochemical properties,biocompatibility,and pharmacokinetic behaviors,allowing for long-term drug circulation and passive targeting.In this study,a novel biomimetic drug delivery system(DDS)against hepatocellular carcinoma was prepared by covering RBCM on GPP-NPs(GA-loaded m PEG-PLA NPs)to develop the RBC@GPP-NPs.In comparison to RBCM-free nanoparticles and free GA,RBC@GPP-NPs improved the drug’s water solubility,stability,safety,and antitumor activity in vivo.We expect that this bionic nanoparticle composite can expand the clinical applicability of GA and provide a feasible solution for the research and development of GA’s nano-formulation.展开更多
AIM： TO investigate the role of Lactobacillus crispatus （L. crispatus） strain China Center for Type Culture Col- lection （CCTCC） M206119 in intestinal inflammation.METHODS： Forty 8-wk-old Balb/c mice （20± ...AIM： TO investigate the role of Lactobacillus crispatus （L. crispatus） strain China Center for Type Culture Col- lection （CCTCC） M206119 in intestinal inflammation.METHODS： Forty 8-wk-old Balb/c mice （20± 2 g） were divided into four groups of 10 mice each. Three groups that had received dextran sulfate sodium （DSS） were administered normal saline, sulfasalazine or CCTCC M206119 strain, and the fourth group received none of these. We assessed the severity of colitis using a disease activity index, measured the colon length and weight, collected stools and mesenteric lymph nodes for bacterial microflora analysis. One centimeter of the proximal colon, middle colon and distal colon were collected and fixed in 10% buffered formalin, dehydrated in ethanol, and embedded in paraffin. Interleukin （IL）- 1β, IL-6 and tumor necrosis factor （TNF）-α expression was detected using reverse transcription polymerase chain reaction. Protective factors zonula occludens （ZO）-1 and β-defensin 2 were detected by immunoblot-ting. The features of CCTCC M206119 strain were identified based on morphology, biochemical profile, and 16S RNA sequencing.RESULTS： DSS-colitis animals treated with CCTCC M206119 had markedly more severe disease, with greater weight loss, diarrhea, fecal bleeding, and shortened colon length. In addition, the CCTCC-M206119- treated group had comparatively higher histologi- cal scores and more neutrophil infiltration than the controls. Expression of protective factors ZO-1 and β-defensin 2 was downregulated due to destruction of the mucosal barrier after CCTCC M206119 strain treatment. An in vitro assay demonstrated that CCTCC M206119 strain increased the nuclear translocation of nuclear factor-κB in epithelial cells. Intestinal proinflam- matory or anti-inflammatory cytokine responses were evaluated. Proinflammatory colonic cytokine （IL-Iβ, IL-6 and TNF-α） levels were clearly increased in CCTCC- M206119-treated animals, whereas anti-inflammatory colonic cytokine （IL-10） level was lowered compared with saline or 5-aminosalicylic-acid-treated DSS-colitis mice. Next, CCTCC M206119 strain was characterized as 1. crispatus by microscopic morphology, biochemical tests and 16S rRNA gene level.CONCLUSION： Not all lactobacilli are beneficial for in- testinal inflammation, and L. crispatus CCTCC M206119 strain is involved in exacerbation of intestinal inflamma- tion in DSS-colitis mice.展开更多
Efficient and accurate access to coastal land cover information is of great significance for marine disaster prevention and mitigation.Although the popular and common sensors of land resource satellites provide free a...Efficient and accurate access to coastal land cover information is of great significance for marine disaster prevention and mitigation.Although the popular and common sensors of land resource satellites provide free and valuable images to map the land cover,coastal areas often encounter significant cloud cover,especially in tropical areas,which makes the classification in those areas non-ideal.To solve this problem,we proposed a framework of combining medium-resolution optical images and synthetic aperture radar(SAR)data with the recently popular object-based image analysis(OBIA)method and used the Landsat Operational Land Imager(OLI)and Phased Array type L-band Synthetic Aperture Radar(PALSAR)images acquired in Singapore in 2017 as a case study.We designed experiments to confirm two critical factors of this framework:one is the segmentation scale that determines the average object size,and the other is the classification feature.Accuracy assessments of the land cover indicated that the optimal segmentation scale was between 40 and 80,and the features of the combination of OLI and SAR resulted in higher accuracy than any individual features,especially in areas with cloud cover.Based on the land cover generated by this framework,we assessed the vulnerability of the marine disasters of Singapore in 2008 and 2017 and found that the high-vulnerability areas mainly located in the southeast and increased by 118.97 km2 over the past decade.To clarify the disaster response plan for different geographical environments,we classified risk based on altitude and distance from shore.The newly increased high-vulnerability regions within 4 km offshore and below 30 m above sea level are at high risk;these regions may need to focus on strengthening disaster prevention construction.This study serves as a typical example of using remote sensing techniques for the vulnerability assessment of marine disasters,especially those in cloudy coastal areas.展开更多
基金supported by the National Natural Science Foundation of China(82141201,82405164,82204878,and 32170872)the Haihe Laboratory of Modern Chinese Medicine(Research and development of a universal treatment formula for respiratory viral infections)+3 种基金the National Key Research and Development Program of China(2021YFC1712905,2021YFC1712904,2020YFA0708004,2021YFE0200300,and 2023YFC2306202)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202002,ZYYCXTD-D-202001)the China Postdoctoral Science Foundation(2023M742626)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(CPSF)(GZC20231927).
文摘The NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome is an intracellular protein complex containing a nucleotide-binding oligomerization domain,leucine-rich repeats,and a pyrin domain.It is a key regulator of inflammation in viral pneumonia(VP).Small-molecule inhibitors targeting various NLRP3 binding sites are advancing into early clinical trials,but their therapeutic utility is incompletely established.Xuanfei Baidu Formula(XF),clinically used for VP treatment,attenuates NLRP3 activation by hampering caspase-11 to impede polarization of pro-inflammatory macrophages in a model of lipopolysaccharide(LPS)-induced lung injury inmice.Herein,we demonstrate that XF attenuated influenza A virus(IAV)-induced lung inflammation as well as lung injury in immunocompetent(but not in macrophage-depleted)mice.RNA sequencing of sorted lung macrophages from IAV-infected mice revealed that XF inhibited activation of the NLRP3 inflammation and interleukin(IL)-1βproduction.Quantitative nuclear magnetic resonance of XF enabled us to develop XF-Comb1,a fixed-ratio combination of five bioactive compounds that recapitulated the bioactivity of XF in suppressing NLRP3 activation in macrophages in vitro and in vivo.Interestingly,XF-Comb1 inhibited assembly of the NLRP3 inflammasome through multi-site interactions with functional residues of NLRP3,apoptosis-associated speck-like protein containing caspase recruitment domain(ASC),and caspase-1.Taken together,this work advances the development of NLRP3 inhibitors by translating a complex herbal formula into defined bioactive compounds.
基金supported by Shenzhen Science and Technology Program(NO.JCYJ20210324094000001).
文摘Perfluoroalkyl and polyfluoroalkyl substances(PFASs)pollution with their toxicity,carcinogenicity,and persistence has been concerned worldwide.Research into novel materials for detecting and removing PFASs has increased rapidly,particularly in regard to the emergence of well-characterized single-atom materials(SAMs).Owing to the high selectivity,high atom utilization,and abundant active sites of SAMs,these materials exhibit remarkable efficacy in the detection and removal of PFASs.In this work,recent advances in the synthesis of SAMs for the detection and removal PFASs are reviewed.In-depth discussions of the structure-activity relationship and reaction mechanisms have demonstrated the high efficiency,activity,and selectivity of SAMs for the detection,adsorption,and degradation of PFASs.To optimize the application of SAMs in PFASs remediation,this review comprehensively surveys SAMs applications for PFASs and analyzes potential design strategies based on synthesis methods and corresponding properties.Synthesis strategies such as wet-chemistry,which offer ease of operation and high potential for large-scale production,are recommended for the further exploration of specific SAMs for the detection and removal of PFASs.Finally,this review identifies the challenges and opportunities for development of SAMs for the detection and remediation of PFASs,providing an outlook on strategic goals for a green economy and sustainable development.
基金supported by the Guangdong Basic and Applied Basic Research Foundation (2022A1515010875)National Natural Science Foundation of China (12404480)+4 种基金Shenzhen Science and Technology Program (JCYJ20240813113238050, JCYJ20240813113306008)Education Department of Guangdong Province (2021KCXTD045)National Natural Science Foundation of China (12274303)the Shenzhen Key Laboratory of Applied Technologies of Super-Diamond and Functional Crystals (ZDSYS20230626091303007)Characteristic Innovation Foundation of Higher Education Institutions of Guangdong Province (2022KTSCX116)
文摘Sequential processing(SqP)of the active layer offers independent optimization of the donor and acceptor with more targeted solvent design,which is considered the most promising strategy for achieving efficient organic solar cells(OSCs).In the SqP method,the favorable interpenetrating network seriously depends on the fine control of the bottom layer swelling.However,the choice of solvent(s)for both the donor and acceptor have been mostly based on a trial-and-error manner.A single solvent often cannot achieve sufficient yet not excessive swelling,which has long been a difficulty in the high efficient SqP OSCs.Herein,two new isomeric molecules are introduced to fine-tune the nucleation and crystallization dynamics that allows judicious control over the swelling of the bottom layer.The strong non-covalent interaction between the isomeric molecule and active materials provides an excellent driving force for optimize the swelling-process.Among them,the molecule with high dipole moment promotes earlier nucleation of the PM6 and provides extended time for crystallization during SqP,improving bulk morphology and vertical phase segregation.As a result,champion efficiencies of 17.38%and 20.00%(certified 19.70%)are achieved based on PM6/PYF-T-o(all-polymer)and PM6/BTP-eC9 devices casted by toluene solvent.
基金supported by the National Natural Science Foundation of China(Nos.41830318 and 51861135305).
文摘Secondary iron-sulfate minerals such as jarosite,which are easily formed in acid mine drainage,play an important role in controlling metal mobility.In this work,the typical iron-oxidizing bacterium Acidithiobacillus ferrooxidans ATCC 23270 was selected to synthesize jarosite in the presence of antimony ions,during which the solution behavior,synthetic product composition,and bacterial metabolism were studied.The results show that in the presence of Sb(V),Fe^(2+)was rapidly oxidized to Fe^(3+)by A.ferrooxidans and Sb(V)had no obvious effect on the biooxidation of Fe^(2+)under the current experimental conditions.The presence of Sb(Ⅲ)inhibited bacterial growth and Fe^(2+)oxidation.For the group with Sb(Ⅲ),products with amorphous phaseswere formed 72 hr later,whichwere mainly ferrous sulfate and pentavalent antimony oxide,and the amorphous precursor was finally transformed into a more stable crystal phase.For the group with Sb(V),the morphology and structure of jarosite were changed in comparison with those without Sb.The biomineralization process was accompanied by the removal of 94%Sb(V)to form jarosite containing the Fe-Sb-O complex.Comparative transcriptome analysis shows differential effects of Sb(Ⅲ)and Sb(V)on bacterial metabolism.The expression levels of functional genes related to cell components were much more downregulated for the group with Sb(Ⅲ)butmuch more regulated for that with Sb(V).Notably,cytochrome c and nitrogen fixation-relevant genes for the A.f_Fe^(2+)_Sb(Ⅲ)group were enhanced significantly,indicating their role in Sb(Ⅲ)resistance.This study is of great value for the development of antimony pollution control and remediation technology.
基金supported by China National Natural Science Foundation of China(52225101)Graduate Research and Innovation Foundation of Chongqing(CYB240017)+1 种基金National Natural Science Foundation of China(82373128)Natural Science Foundation of Chongqing,China(2024MSXM174)for Shixiang Guo.
文摘Biodegradable magnesium alloys show promising potential for pancreatic duct stents,yet their degradation varies significantly across physiological environments.This study compared the corrosion rates of extruded Mg-2Zn-xMn(x=0,0.5,1.0,1.5 wt.%)alloys in human pancreatic fluid.The results revealed that the alloys undergo different corrosion mechanisms in human pancreatic fluid,emphasizing the necessity of conducting evaluations under physiologically relevant conditions.Further investigations into the degradation mechanism in pancreatic fluid indicated that the alkaline PH(8.3–8.7),high bicarbonate concentration,and enzymatic activity significantly influence the corrosion process.Electrochemical and immersion tests showed rapid initial corrosion due to Cl^(−)attack,followed by the formation of a protective Mg(OH)_(2),MgCO_(3),and Ca_(3)(PO_(4))_(2)layer that slowed degradation.However,digestive enzymes,particularly trypsin,disrupt passivation by interacting with organic components,leading to pitting and filiform corrosion.Among the investigated alloys,Mg-2Zn-1.0Mn exhibited the most favorable combination of corrosion resistance,mechanical performance,and cytocompatibility.This study highlights the critical impact of pancreatic fluid on magnesium alloy degradation and stresses the need for physiologically accurate evaluations.
基金supported by the National Natural Science Foundation of China,82471345(to LC)the Key Research and Development Program for Social Development by the Jiangsu Provincial Department of Science and Technology.No.BE2022668(to LC).
文摘Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.
基金supported in part by the National Natural Science Foundation of China,No.81573644(to LMH),81573733(to SWX)the Tianjin 131 Innovative Team Project,China(to HW)+5 种基金the National Major Science and Technology Project of China,No.2012ZX09101201-004(to SWX)the Science and Technology Plan Project of Tianjin of China,No.16PTSYJC00120(to LMH)the Applied Foundation and Frontier Technology Research Program of Tianjin of China(General Project),No.14JCYBJC28900(to SXW)the National International Science and Technology Cooperation Project of China,No.2015DFA30430(to HW)the Key Program of the Natural Science Foundation of Tianjin of China,No.16ICZDJC36300(to HW)the Scientific Research and Technology Development Plan Project of Guangxi Zhuang Autonomous Region of China,No.14125008-2-5(to SXW)
文摘Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells(bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N_2/5% CO_2 for 6 hours, followed by high-glucose medium containing 95% O_2 and 5% CO_2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations(diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1β, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1β, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway.
基金supported by the National Natural Science Foundation(52302284,22002086,22204096)Shanghai Sailing Program(23YF1412200)the Fundamental Research Funds for the Central Universities(22120240314).
文摘Single-atom catalysts(SACs)have garnered significant attention in lithium-sulfur(Li-S)batteries for their potential to mitigate the severe polysulfide shuttle effect and sluggish redox kinetics.However,the development of highly efficient SACs and a comprehensive understanding of their structure-activity relationships remain enormously challenging.Herein,a novel kind of Fe-based SAC featuring an asymmetric FeN_(5)-TeN_(4) coordination structure was precisely designed by introducing Te atom adjacent to the Fe active center to enhance the catalytic activity.Theoretical calculations reveal that the neighboring Te atom modulates the local coordination environment of the central Fe site,elevating the d-band center closer to the Fermi level and strengthening the d-p orbital hybridization between the catalyst and sulfur species,thereby immobilizing polysulfides and improving the bidirectional catalysis of Li-S redox.Consequently,the Fe-Te atom pair catalyst endows Li-S batteries with exceptional rate performance,achieving a high specific capacity of 735 mAh g^(−1) at 5 C,and remarkable cycling stability with a low decay rate of 0.038%per cycle over 1000 cycles at 1 C.This work provides fundamental insights into the electronic structure modulation of SACs and establishes a clear correlation between precisely engineered atomic configurations and their enhanced catalytic performance in Li-S electrochemistry.
基金the China National Science&Technology Pillar Program(2011BAI11B01)the National Health and Family Planning Commission,China(No.201402002)the CAMS Innovation Fund for Medical Sciences(2017-I2M-1-004)。
文摘Background Heart failure(HF)is a leading cause of hospitalization and mortality for older chronic kidney disease(CKD)patients.However,the epidemiological data is scarce.We aimed to determine the prevalence of left ventricular(LV)dysfunction and HF,and to explore the risk factors for HF among those patients.Methods This is a cross-sectional analysis of the China Hypertension Survey conducted between October 2012 and December 2015.A total of 5,808 participants aged≥65 years were included in the analysis.Self-reported history of HF and any other cardiovascular diseases was acquired.2-D and Doppler echocardiography were used to assess LV dysfunction.CKD was defined as either estimated glomerular filtration rate(eGFR)<60 mL/min per 1.73 m2 or urinary albumin to creatinine ratio(ACR)≥30 mg/g.Results Among CKD patients aged≥65 years,the weighted prevalence of HF,heart failure with preserved ejection fraction(HFpEF),heart failure with mid-range ejection fraction(HFmrEF),and heart failure with reduced ejection fraction(HFrEF)was 4.8%,2.5%,0.8%,and 1.7%,respectively.The weighted prevalence of HF was 5.0%in patients with eGFR<60 mL/min per 1.73 m2,and was 5.9%in patients with ACR≥30 mg/g.The prevalence of LV systolic dysfunction was 3.1%,and while it was 8.9%for moderate/severe diastolic dysfunction.Multivariate analysis showed that smoking was significantly associated with the risk of HF.Furthermore,age,smoking,and residents in rural areas were significantly associated with a risk of LV diastolic dysfunction.Conclusions The prevalence of HF and LV dysfunction was high in older patients with CKD,suggesting that particular strategies will be required.
基金Supported by the National Natural Science Foundation of China,No.81570535 and No.81770587Key Projects in the National Science and Technology Pillar Program during the Thirteenth Five-year Plan Period,No.2017ZX10203201-008,No.2018ZX09206005-003,and 2017ZX10202202-005-004+4 种基金the Shanghai Three-Year Plan of the Clinical Skills and Innovations,No.16CR1002Athe Shanghai Municipal Key Clinical Specialty,No.shslczdzk01103the Shanghai Three-Year Plan of the Key Subjects Construction in Public Health-Infectious Diseases and Pathogenic Microorganism,No.15GWZK0102the Suzhou Expert Team of Clinical Medicine,No.SZYJTD201717the Joint Research Initiative-Shanghai Jiao Tong University School of Medicine,No.YW20190002
文摘BACKGROUND Reports on bacterial infection(BI)in decompensated cirrhosis(DC)is mainly from alcoholic cirrhosis.The role of BI as a trigger or complication of acute-onchronic liver failure(ACLF)in patients with hepatitis B virus decompensated cirrhosis(HBV-DC)remains to be investigated.AIM To investigate the impact of BI on the outcomes of the patients with HBV-DC admitted into the hospital with or without ACLF.METHODS This retrospective study included patients with HBV-DC admitted to two tertiary centers in China.In-hospital overall survival,90-d transplant-free survival,5-year post-discharge survival,and cumulative incidence of ACLF were evaluated.Risk factors for death were analyzed considering liver transplantation as a competing event.RESULTS A total of 1281 hospitalized HBV-DC patients were included;284 had ACLF at admission.The overall prevalence of BI was 28.1%.The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without,in both the patients admitted with and without ACLF.The presence of BI significantly increased the risk of developing ACLF[subdistribution hazard ratio(sHR)=2.52,95%CI:1.75-3.61,P<0.001]in the patients without ACLF.In the patients discharged alive,those who had an episode of BI had a significantly lower 5-year transplant-free survival.BI was an independent risk factor for death in the patients admitted without ACLF(sHR=3.28,95%CI:1.93-5.57),while in ACLF admissions,the presence of pneumonia,but not other type of BI,independently increased the risk of death(sHR=1.87,95%CI:1.24-2.82).CONCLUSION BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival.HBV-DC patients should be monitored carefully for the development of BI,especially pneumonia,to avoid an adverse outcome.
基金supported by the National Natural Science Foundation of China(Grant Nos.81972656 and 31671421)the Key Project of Tianjin Natural Science Foundation(Grant No.18JCZDJC35200)+1 种基金the State Key Project on Infectious Diseases of China(Grant No.2018ZX10723204)the National 135 Major Project of China(2018ZX10302205)。
文摘Objective:Hepatocellular carcinoma(HCC)is a lethal global disease that requires an accurate diagnosis.We assessed the potential of 5 serum biomarkers(AFP,AFU,GGT-II,GPC3,and HGF)in the diagnosis of HCC.Methods:In this retrospective study,we measured the serum levels of each biomarker using ELISAs in 921 participants,including 298 patients with HCC,154 patients with chronic hepatitis(CH),122 patients with liver cirrhosis(LC),and 347 healthy controls from 3 hospitals.Patients negative for hepatitis B surface antigen and hepatitis C antibody(called"NBNC-HCC")and patients positive for the above indices(called"HBV-HCC and HCV-HCC")were enrolled.The selected diagnostic model was constructed using a training cohort(n=468),and a validation cohort(n=453)was used to validate our results.Receiver operating characteristic analysis was used to evaluate the diagnostic accuracy.Results:Theα-L-fucosidase(AFU)/α-fetoprotein(AFP)combination was best able to distinguish NBNC-HCC[area under the curve:0.986(95%confidence interval:0.958–0.997),sensitivity:92.6%,specificity:98.9%]from healthy controls in the test cohort.For screening populations at risk of developing HCC(CH and LC),the AFP/AFU combination improved the diagnostic specificity for early-stage HCC[area under the curve:0.776(0.712–0.831),sensitivity:52.5%,specificity:91.6%in the test group].In all-stage HBV-HCC and HCV-HCC,AFU was also the best candidate biomarker combined with AFP[area under the curve:0.835(0.784–0.877),sensitivity 69.1%,specificity:87.4%in the test group].All results were verified in the validation group.Conclusions:The AFP/AFU combination could be used to identify NBNC-HCC from healthy controls and hepatitis-related HCC from at-risk patients.
基金financially supported by the National Natural Science Foundation of China(No.51574129)。
文摘The influence of squeeze casting pressure on nanoparticle distribution and mechanical properties of 2 wt.%nano-SiC_(p)/Al−Cu composites assisted with ultrasonic vibration was investigated.Results show that as the applied pressure increases from 0 to 400 MPa,theα(Al)grains are significantly refined at first and then the refinement trend slows down,and the porosity of composites is gradually reduced.When the applied pressure is 400 MPa,α(Al)grain size is reduced from 105 to 25μm,and the nanoparticle distribution is significantly improved,resulting in the optimal mechanical properties of the composites.The ultimate tensile strength,yield strength and elongation of the composites are 290 MPa,182 MPa and 10%,which are 52.6%,25.5%and 400%higher than those of the nano-SiC_(p)/Al−Cu composites prepared by gravity casting(0 MPa).The enhancement in strength and elongation of nano-SiC_(p)/Al−Cu composites under high pressure is mainly attributed to grain refinement,reduction of porosity and uniform distribution of nanoparticles.
基金Supported by the National Key Research and Development Program of China(No.2016YFC1402003)the National Natural Science Foundation of China(No.41671436)the Innovation Project of LREIS(No.O88RAA01YA)
文摘Sanduao is an important sea-breeding bay in Fujian,South China and holds a high economic status in aquaculture.Quickly and accurately obtaining information including the distribution area,quantity,and aquaculture area is important for breeding area planning,production value estimation,ecological survey,and storm surge prevention.However,as the aquaculture area expands,the seawater background becomes increasingly complex and spectral characteristics differ dramatically,making it difficult to determine the aquaculture area.In this study,we used a high-resolution remote-sensing satellite GF-2 image to introduce a deep-learning Richer Convolutional Features(RCF)network model to extract the aquaculture area.Then we used the density of aquaculture as an assessment index to assess the vulnerability of aquaculture areas in Sanduao.The results demonstrate that this method does not require land and water separation of the area in advance,and good extraction can be achieved in the areas with more sediment and waves,with an extraction accuracy>93%,which is suitable for large-scale aquaculture area extraction.Vulnerability assessment results indicate that the density of aquaculture in the eastern part of Sanduao is considerably high,reaching a higher vulnerability level than other parts.
基金the author(s).This work was financially supported by the National Natural.Science Foundation of China(Nos.51864013 and 52074095)Also,this project supported by National Natural Science Foundation of Guizhou Province with grant No.[2019]1086.
文摘Aluminum oxide inclusions in SWRS82B steel seriously affect the drawing performance of steel strands.The effects of different addition amounts of yttrium(within the range of 0%–0.026%)on the composition,morphology,size and spacing of aluminum oxide inclusions were studied by scanning electron microscopy and energy spectrum analysis.Based on classical thermodynamics and FactSage software,the predominance diagram of inclusions in Fe–O–S–Y system and the effect of the addition of rare earth yttrium on the stability of alumina inclusions were calculated.The results showed that molten steel was modified by adding the rare earth element yttrium.It can be inferred that the approximate route of target inclusion modification was:Al_(2)O_(3)→Y_(2)S_(3)+YAlO_(3)+Al_(2)O_(3)→Y_(2)S_(3)+YAlO_(3)+Y_(2)O_(2)S+YAlO_(3)+Al_(2)O_(3)→Y_(2)S_(3)+Y_(2)O_(2)S.The experimental samples with 0.026%added yttrium had the best inclusion characteristics,in which the inclusion surface density distribution was uniform,and the interfacial distance between inclusions was mainly in the range of 100–500μm.After modification,the average inclusion size in molten steel was reduced by 6.9–8.6μm.The mechanism of yttrium modification was discussed based on actual calculation results and experimental results.
基金Supported by The National Natural Science Foundation of China,No.82173317The Scientific Research Projects of Tianjin Education Commission,No.2022KJ227The Doctoral Start-up Fund of Tianjin Medical University Cancer Institute&Hospital,No.B2208.
文摘BACKGROUND Bevacizumab and sintilimab combined interventional treatment(BeSiIT)and L envatinib and sintilimab combined interventional treatment(LeSiIT)are two commonly used therapeutic regimens for intermediate-advanced hepatocellular carcinoma(HCC)in clinical practice.AIM To compare the clinical efficacy and safety of BeSiIT and LeSiIT for the treatment of intermediate and advanced HCC.METHODS Patients diagnosed with intermediate-advanced HCC and initially treated with BeSiIT or LeSiIT in the Tianjin Medical University Cancer Institute and Hospital between February 2020 and July 2021 were included.The primary endpoint was progression-free survival(PFS),and the secondary endpoints were overall survival(OS),objective response rate(ORR),disease control rate(DCR),conversion rate,and treatmentrelated adverse events.RESULTS Total 127 patients met the inclusion criteria and were divided into BeSiIT and LeSiIT groups.Twenty-eight and fifty patients in the BeSiIT and LeSiIT groups,respectively,were assessed after 1:2 propensity score matching.PFS and OS rates were not significantly different between the two groups.No significant variations were noted in ORRs or DCRs according to the Response Evaluation Criteria in Solid Tumors(RECIST),and modified RECIST.BeSiIT group showed a better conversion rate than the LeSiIT group(P=0.043).Both groups showed manageable toxicity profiles.Multivariate analysis showed that the independent factors associated with PFS were alphafetoprotein levels and carcinoembryonic antigen score.CONCLUSION In intermediate-to-advanced HCC,the BeSiIT and LeSiIT groups exhibited acceptable toxicities and comparable PFS,OS,and ORR.
基金the National Key R&D Program of China(No.2019YFC1711000)the National Natural Science Foundation(No.31600171)+1 种基金the Shenzhen Urban Management Bureau Fund(No.201520)the Shenzhen Municipal Government of China(No.JCYJ20170817145512467)。
文摘Magnolia biondii Pamp.(Magnoliaceae,magnoliids)is a phylogenetically,economically,and medicinally important ornamental tree species widely grown and cultivated in the north-temperate regions of China.Determining the genome sequence of M.biondii would help resolve the phylogenetic uncertainty of magnoliids and improve the understanding of individual trait evolution within the Magnolia genus.We assembled a chromosome-level reference genome of M.biondii using~67,~175,and~154Gb of raw DNA sequences generated via Pacific Biosciences single-molecule real-time sequencing,10X Genomics Chromium,and Hi-C scaffolding strategies,respectively.The final genome assembly was~2.22Gb,with a contig N50 value of 269.11 kb and a BUSCO complete gene percentage of 91.90%.Approximately 89.17%of the genome was organized into 19 chromosomes,resulting in a scaffold N50 of 92.86Mb.The genome contained 47,547 protein-coding genes,accounting for 23.47%of the genome length,whereas 66.48%of the genome length consisted of repetitive elements.We confirmed a WGD event that occurred very close to the time of the split between the Magnoliales and Laurales.Functional enrichment of the Magnolia-specific and expanded gene families highlighted genes involved in the biosynthesis of secondary metabolites,plant–pathogen interactions,and responses to stimuli,which may improve the ecological fitness and biological adaptability of the lineage.Phylogenomic analyses revealed a sister relationship of magnoliids and Chloranthaceae,which are sister to a clade comprising monocots and eudicots.The genome sequence of M.biondii could lead to trait improvement,germplasm conservation,and evolutionary studies on the rapid radiation of early angiosperms.
基金supported by the National Natural Science Foundation of China(No.81900339)Key Research and Development Program of Science and Technology Department of Sichuan Province(No.2019YFS0514)Health Commission of Sichuan Province(No.20PJ095)。
文摘Gambogic acid(GA)is a potential clinical anticancer drug that can exert antitumor effects via various molecular mechanisms.Notwithstanding,GA’s low water solubility,poor stability,short half-life,and unavoidable toxic side effects have significantly hampered its clinical application.Erythrocyte membranecoated nanoparticles(RBCM-NPs)improve drug’s physicochemical properties,biocompatibility,and pharmacokinetic behaviors,allowing for long-term drug circulation and passive targeting.In this study,a novel biomimetic drug delivery system(DDS)against hepatocellular carcinoma was prepared by covering RBCM on GPP-NPs(GA-loaded m PEG-PLA NPs)to develop the RBC@GPP-NPs.In comparison to RBCM-free nanoparticles and free GA,RBC@GPP-NPs improved the drug’s water solubility,stability,safety,and antitumor activity in vivo.We expect that this bionic nanoparticle composite can expand the clinical applicability of GA and provide a feasible solution for the research and development of GA’s nano-formulation.
文摘AIM： TO investigate the role of Lactobacillus crispatus （L. crispatus） strain China Center for Type Culture Col- lection （CCTCC） M206119 in intestinal inflammation.METHODS： Forty 8-wk-old Balb/c mice （20± 2 g） were divided into four groups of 10 mice each. Three groups that had received dextran sulfate sodium （DSS） were administered normal saline, sulfasalazine or CCTCC M206119 strain, and the fourth group received none of these. We assessed the severity of colitis using a disease activity index, measured the colon length and weight, collected stools and mesenteric lymph nodes for bacterial microflora analysis. One centimeter of the proximal colon, middle colon and distal colon were collected and fixed in 10% buffered formalin, dehydrated in ethanol, and embedded in paraffin. Interleukin （IL）- 1β, IL-6 and tumor necrosis factor （TNF）-α expression was detected using reverse transcription polymerase chain reaction. Protective factors zonula occludens （ZO）-1 and β-defensin 2 were detected by immunoblot-ting. The features of CCTCC M206119 strain were identified based on morphology, biochemical profile, and 16S RNA sequencing.RESULTS： DSS-colitis animals treated with CCTCC M206119 had markedly more severe disease, with greater weight loss, diarrhea, fecal bleeding, and shortened colon length. In addition, the CCTCC-M206119- treated group had comparatively higher histologi- cal scores and more neutrophil infiltration than the controls. Expression of protective factors ZO-1 and β-defensin 2 was downregulated due to destruction of the mucosal barrier after CCTCC M206119 strain treatment. An in vitro assay demonstrated that CCTCC M206119 strain increased the nuclear translocation of nuclear factor-κB in epithelial cells. Intestinal proinflam- matory or anti-inflammatory cytokine responses were evaluated. Proinflammatory colonic cytokine （IL-Iβ, IL-6 and TNF-α） levels were clearly increased in CCTCC- M206119-treated animals, whereas anti-inflammatory colonic cytokine （IL-10） level was lowered compared with saline or 5-aminosalicylic-acid-treated DSS-colitis mice. Next, CCTCC M206119 strain was characterized as 1. crispatus by microscopic morphology, biochemical tests and 16S rRNA gene level.CONCLUSION： Not all lactobacilli are beneficial for in- testinal inflammation, and L. crispatus CCTCC M206119 strain is involved in exacerbation of intestinal inflamma- tion in DSS-colitis mice.
基金Supported by the National Key Research and Development Program of China(No.2016YFC1402003)the CAS Earth Big Data Science Project(No.XDA19060303)the Innovation Project of the State Key Laboratory of Resources and Environmental Information System(No.O88RAA01YA)
文摘Efficient and accurate access to coastal land cover information is of great significance for marine disaster prevention and mitigation.Although the popular and common sensors of land resource satellites provide free and valuable images to map the land cover,coastal areas often encounter significant cloud cover,especially in tropical areas,which makes the classification in those areas non-ideal.To solve this problem,we proposed a framework of combining medium-resolution optical images and synthetic aperture radar(SAR)data with the recently popular object-based image analysis(OBIA)method and used the Landsat Operational Land Imager(OLI)and Phased Array type L-band Synthetic Aperture Radar(PALSAR)images acquired in Singapore in 2017 as a case study.We designed experiments to confirm two critical factors of this framework:one is the segmentation scale that determines the average object size,and the other is the classification feature.Accuracy assessments of the land cover indicated that the optimal segmentation scale was between 40 and 80,and the features of the combination of OLI and SAR resulted in higher accuracy than any individual features,especially in areas with cloud cover.Based on the land cover generated by this framework,we assessed the vulnerability of the marine disasters of Singapore in 2008 and 2017 and found that the high-vulnerability areas mainly located in the southeast and increased by 118.97 km2 over the past decade.To clarify the disaster response plan for different geographical environments,we classified risk based on altitude and distance from shore.The newly increased high-vulnerability regions within 4 km offshore and below 30 m above sea level are at high risk;these regions may need to focus on strengthening disaster prevention construction.This study serves as a typical example of using remote sensing techniques for the vulnerability assessment of marine disasters,especially those in cloudy coastal areas.
