Although anisotropic NMR spectroscopy has emerged as a powerful method for determining the relative configuration of complex natural products,major challenges persist with structurally flexible molecules.In this study...Although anisotropic NMR spectroscopy has emerged as a powerful method for determining the relative configuration of complex natural products,major challenges persist with structurally flexible molecules.In this study,we conducted a system-atic comparative analysis of stereochemical elucidation,combining anisotropic NMR spectroscopy and density functional theory(DFT)calculations on spiroepicoccin B(1)and epicoccin V(2),which were characterized as thiodiketopiperazine marine natural products isolated from the deep-sea-derived fungus Epicoccum nigrum SD-388.For the flexible compound 2,we compared various conformational sampling approaches,including an assessment of the quality of relative energies within the obtained ensembles.We demonstrated the critical role of dispersion correction within DFT computations to precisely account for weak non-bonded intramolecular interactions.By integrating anisotropic NMR analysis,chemical shifts,elec-tronic circular dichroism,and DFT computations,we determined the absolute configurations and conformational ensembles for 1 and 2,respectively,highlighting the significance of the intramolecular methyl-πinteraction in stabilizing one of the conformers.Our study introduces new strategies to address conformational flexibility in the stereochemical elucidation of challenging organic molecules.展开更多
Although numerous studies have proposed explanations for the specific and relative effects of stand structure,plant diversity,and environmental conditions on carbon(C)storage in forest ecosystems,understanding how the...Although numerous studies have proposed explanations for the specific and relative effects of stand structure,plant diversity,and environmental conditions on carbon(C)storage in forest ecosystems,understanding how these factors collectively affect C storage in different community layers(trees,shrubs,and herbs)and forest types(mixed,broad-leaved(E),broad-leaved(M),and coniferous forest)continues to pose challenges.To address this,we used structural equation models to quantify the influence of biotic factors(mean DBH,mean height,maximum height,stem density,and basal area)and abiotic factors(elevation and canopy openness),as well as metrics of species diversity(Shannon–Wiener index,Simpson index,and Pielou’s evenness)in various forest types.Our analysis revealed the critical roles of forest types and elevation in explaining a substantial portion of variability in C storage in the overstory layer,with a moderate influence of stand factors(mean DBH and basal area)and a slightly negative impact of tree species diversity(Shannon–Wiener index).Notably,forest height emerged as the primary predictor of C storage in the herb layer.Regression relationships further highlighted the significant contribution of tree species diversity to mean height,understory C storage,and branch biomass within the forest ecosystem.Our insights into tree species diversity,derived from structural equation modeling of C storage in the overstory,suggest that the effects of tree species diversity may be influenced by stem biomass in statistical reasoning within temperate forests.Further research should also integrate tree species diversity with tree components biomass,forest mean height,understory C,and canopy openness to understand complex relationships and maintain healthy and sustainable ecosystems in the face of global climate challenges.展开更多
The machine learning models of multiple linear regression(MLR),support vector regression(SVR),and extreme learning ma-chine(ELM)and the proposed ELM models of online sequential ELM(OS-ELM)and OS-ELM with forgetting me...The machine learning models of multiple linear regression(MLR),support vector regression(SVR),and extreme learning ma-chine(ELM)and the proposed ELM models of online sequential ELM(OS-ELM)and OS-ELM with forgetting mechanism(FOS-ELM)are applied in the prediction of the lime utilization ratio of dephosphorization in the basic oxygen furnace steelmaking process.The ELM model exhibites the best performance compared with the models of MLR and SVR.OS-ELM and FOS-ELM are applied for sequential learning and model updating.The optimal number of samples in validity term of the FOS-ELM model is determined to be 1500,with the smallest population mean absolute relative error(MARE)value of 0.058226 for the population.The variable importance analysis reveals lime weight,initial P content,and hot metal weight as the most important variables for the lime utilization ratio.The lime utilization ratio increases with the decrease in lime weight and the increases in the initial P content and hot metal weight.A prediction system based on FOS-ELM is applied in actual industrial production for one month.The hit ratios of the predicted lime utilization ratio in the error ranges of±1%,±3%,and±5%are 61.16%,90.63%,and 94.11%,respectively.The coefficient of determination,MARE,and root mean square error are 0.8670,0.06823,and 1.4265,respectively.The system exhibits desirable performance for applications in actual industrial pro-duction.展开更多
This work focuses on the influence of Al content on the precipitation of nanoprecipitates,growth of prior austenite grains(PAGs),and impact toughness in simulated coarse-grained heat-affected zones (CGHAZs) of two exp...This work focuses on the influence of Al content on the precipitation of nanoprecipitates,growth of prior austenite grains(PAGs),and impact toughness in simulated coarse-grained heat-affected zones (CGHAZs) of two experimental shipbuilding steels after being subjected to high-heat input welding at 400 kJ·cm^(-1).The base metals (BMs) of both steels contained three types of precipitates Type Ⅰ:cubic (Ti,Nb)(C,N),Type Ⅱ:precipitate with cubic (Ti,Nb)(C,N) core and Nb-rich cap,and Type Ⅲ:ellipsoidal Nb-rich precipitate.In the BM of 60Al and 160Al steels,the number densities of the precipitates were 11.37×10^(5) and 13.88×10^(5) mm^(-2),respectively The 60Al and 160Al steel contained 38.12% and 6.39% Type Ⅲ precipitates,respectively.The difference in the content of Type Ⅲ precipitates in the 60Al steel reduced the pinning effect at the elevated temperature of the CGHAZ,which facilitated the growth of PAGs The average PAG sizes in the CGHAZ of the 60Al and 160Al steels were 189.73 and 174.7μm,respectively.In the 60Al steel,the low lattice mismatch among Cu_(2)S,TiN,and γ-Al_(2)O_(3)facilitated the precipitation of Cu_(2)S and TiN onto γ-Al_(2)O_(3)during welding,which decreased the number density of independently precipitated (Ti,Nb)(C,N) particles but increased that of γ-Al_(2)O_(3)–Ti N–Cu_(2)S particles.Thus abnormally large PAGs formed in the CGHAZ of the 60Al steel,and they reached a maximum size of 1 mm.These PAGs greatly reduced the microstructural homogeneity and consequently decreased the impact toughness from 134 (0.016wt%Al) to 54 J (0.006wt%Al)at-40℃.展开更多
BACKGROUND Colorectal polyps are precancerous diseases of colorectal cancer.Early detection and resection of colorectal polyps can effectively reduce the mortality of colorectal cancer.Endoscopic mucosal resection(EMR...BACKGROUND Colorectal polyps are precancerous diseases of colorectal cancer.Early detection and resection of colorectal polyps can effectively reduce the mortality of colorectal cancer.Endoscopic mucosal resection(EMR)is a common polypectomy proce-dure in clinical practice,but it has a high postoperative recurrence rate.Currently,there is no predictive model for the recurrence of colorectal polyps after EMR.AIM To construct and validate a machine learning(ML)model for predicting the risk of colorectal polyp recurrence one year after EMR.METHODS This study retrospectively collected data from 1694 patients at three medical centers in Xuzhou.Additionally,a total of 166 patients were collected to form a prospective validation set.Feature variable screening was conducted using uni-variate and multivariate logistic regression analyses,and five ML algorithms were used to construct the predictive models.The optimal models were evaluated based on different performance metrics.Decision curve analysis(DCA)and SHapley Additive exPlanation(SHAP)analysis were performed to assess clinical applicability and predictor importance.RESULTS Multivariate logistic regression analysis identified 8 independent risk factors for colorectal polyp recurrence one year after EMR(P<0.05).Among the models,eXtreme Gradient Boosting(XGBoost)demonstrated the highest area under the curve(AUC)in the training set,internal validation set,and prospective validation set,with AUCs of 0.909(95%CI:0.89-0.92),0.921(95%CI:0.90-0.94),and 0.963(95%CI:0.94-0.99),respectively.DCA indicated favorable clinical utility for the XGBoost model.SHAP analysis identified smoking history,family history,and age as the top three most important predictors in the model.CONCLUSION The XGBoost model has the best predictive performance and can assist clinicians in providing individualized colonoscopy follow-up recommendations.展开更多
Tumor vaccine therapy offers significant advantages over conventional treatments,including reduced toxic side effects.However,it currently functions primarily as an adjuvant treatment modality in clinical oncology due...Tumor vaccine therapy offers significant advantages over conventional treatments,including reduced toxic side effects.However,it currently functions primarily as an adjuvant treatment modality in clinical oncology due to limitations in tumor antigen selection and delivery methods.Tumor vaccines often fail to elicit a sufficiently robust immune response against progressive tumors,thereby limiting their clinical efficacy.In this study,we developed a nanoparticle-based tumor vaccine,OVA@HA-PEI,utilizing ovalbumin(OVA)as the presenting antigen and hyaluronic acid(HA)and polyethyleneimine(PEI)as adjuvants and carriers.This formulation significantly enhanced the proliferation of immune cells and cytokines,such as CD3,CD8,interferon-,and tumor necrosis factor-,in vivo,effectively activating an immune response against B16–F10 tumors.In vivofluorescenceflow cytometry(IVFC)has already become an effective method for monitoring circulating tumor cells(CTCs)due to its direct,noninvasive,and long-term detection capabilities.Our study utilized a laboratory-constructed IVFC system to monitor the immune processes induced by the OVA@HA-PEI tumor vaccine and an anti-programmed death-1(PD-1)antibody.The results demonstrated that the combined treatment of OVA@HA-PEI and anti-PD-1 antibody significantly improved the survival time of mice compared to anti-PD-1 antibody treatment alone.Additionally,this combination therapy substantially reduced the number of CTCs in vivo,increased the clearance rate of CTCs by the immune system,and slowed tumor progression.Thesefindings greatly enhance the clinical application prospects of IVFC and tumor vaccines.展开更多
Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)reg...Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.展开更多
At low basicity and low temperature, the dephosphorization behavior and phosphorus distribution ratio(LP) between slag and molten steel in the double slag and remaining slag process were studied with a 180 t basic oxy...At low basicity and low temperature, the dephosphorization behavior and phosphorus distribution ratio(LP) between slag and molten steel in the double slag and remaining slag process were studied with a 180 t basic oxygen furnace industrial experiment.The dephosphorization slags with different basicities were quantitatively analyzed.At the lower basicity range of 0.9–2.59, both LP and dephosphorization ratio were increased as the basicity of dephosphorization slag increased.Dephosphorization slag consisted of dark gray P-rich, light gray liquid slag,and white Fe-rich phases.With increasing basicity, not only did the morphologies of different phases in the dephosphorization slag change greatly, but the area fractions and P2O5 content of the P-rich phase also increased.The transfer route of P during dephosphorization can be deduced as hot metal → liquid slag phase + Fe-rich phase → P-rich phase.展开更多
RuPt/AC bimetallic catalysts were pre pared by two-step incipient impregnation method and evaluated in the hydrogenation of phthalates.According to the characterization results,well dispersed Ru Pt bimetallic nanopart...RuPt/AC bimetallic catalysts were pre pared by two-step incipient impregnation method and evaluated in the hydrogenation of phthalates.According to the characterization results,well dispersed Ru Pt bimetallic nanoparticles were formed on the catalyst,and the strong interaction between the two metals resulted in the formation of RuPt alloy.It was found that Ru can donate electrons to Pt on RuPt alloy nanoparticles,leading to the formation of electron-deficient Ru which significantly promotes the hydrogenation rate of dioctyl phthalate and improves the selectivity of dioctyl di-2-ethylhexylcyclohexane-1,4-dicarboxylate by accelerating the further hydrogenation of intermediate products.The bimetallic RuPt catalyst also presented excellent stability and versatility in the hydrogenation of phthalates,demonstrating its prospective future in the hydrogenation of aromatic ring contained compounds.展开更多
Background:Metabolic scaling theory(MST)is still in debate because observed allometric exponents often deviate from MST predictions,and can change significantly depending on environment,phylogeny,and disturbance.We as...Background:Metabolic scaling theory(MST)is still in debate because observed allometric exponents often deviate from MST predictions,and can change significantly depending on environment,phylogeny,and disturbance.We assembled published scaling exponents from literatures for three allometric relationships linked to biomass allocation:leaf biomassdiameter(LD),stem biomassdiameter(SD),and root biomassdiameter(RD).We used data from natural forests and plantations across China to test the following hypotheses:1)the allometric relationships of trees support the predictions of MST on a broad scale;2)the observed deviations from MST predictions are caused by climate,biotic factors,and/or phylogeny;3)abiotic and biotic factors influence allometric relationships in plantations and natural forests differently,and different allometric relationships(i.e.LD,SD,and RD)are affected differently.We related these scaling exponents to geographic climate gradient,successional stage,stand density,leaf form and phenology,and phylogeny.We used mixedeffect models to examine the major factors affecting tree allometries.Results:In natural forests,SD and RD scaling exponents were consistent with MST predictions in primary forests,but were significantly lower in secondary forests.Both SD and RD scaling exponents in plantations had a medium value that fell between those of the secondary and primary forests,despite plantations being similar in species characteristics and age to secondary forests.The SD and RD exponents were significantly affected by factors that are not yet considered in MST,including winter coldness which explained 2.76%–3.24%of variations,successional stage(7.91%–8.20%of variations),density(a surrogate for competition,5.86%–8.54%of variations),and especially phylogeny(45.86%–56.64%of variations explained).However,the LD scaling exponents conformed to MST predictions in primary,secondary,and plantation forests,and was not strongly explained by most factors.Conclusion:MST is only applicable to primary(steadystate)forests,and climate,biotic factors and phylogeny are causes of the observed deviations of allometric relationships from MST predictions.Forest management practices in plantations have a strong influence on tree allometries.LD allometry is more strongly controlled by biophysical constraints than SD and RD allometries,however,the mechanisms behind this difference still need further examinations.展开更多
Sulfonic acid functionalized mesoporous SBA-15 was prepared using the grafting method.The structure and acid properties were comprehensively characterized using multi-nuclear and quantitative probe molecule solid-stat...Sulfonic acid functionalized mesoporous SBA-15 was prepared using the grafting method.The structure and acid properties were comprehensively characterized using multi-nuclear and quantitative probe molecule solid-state NMR(SSNMR),together with powder X-ray diffraction(XRD),scanning electron microscope(SEM),transmission electron microscopy(TEM),N2 adsorption-desorption techniques.Its catalytic performance in the conversion of fructose to 5-hydroxymethylfurfural(HMF)in dimethyl sulfoxide(DMSO)was studied.Catalyst dosage,reaction time,reaction temperature and solvent effect have been investigated.A high yield of HMF up to 93%was obtained at a relatively low temperature of 373 K for 180 min.The Brønsted acid of SBA-15_SO3H together with the solvent DMSO was found to synergistically catalyze the reaction.The catalyst preserved most of its activity after five times reuse and the catalytic activity can be recovered by H2O2 process.展开更多
Background:Myocardial infarctions(MI)is a major threat to human health especially in people exposed to cold environment.The polarization of macrophages towards different functional phenotypes(M1 macrophages and M2 mac...Background:Myocardial infarctions(MI)is a major threat to human health especially in people exposed to cold environment.The polarization of macrophages towards different functional phenotypes(M1 macrophages and M2 macrophages)is closely related to MI repairment.The growth differentiation factor 11(GDF11)has been reported to play a momentous role in inflammatory associated diseases.In this study,we examined the regulatory role of GDF11 in macrophage polarization and elucidated the underlying mechanisms in MI.Methods:In vivo,the mice model of MI was induced by permanent ligation of the left anterior descending coronary artery(LAD),and mice were randomly divided into the sham group,MI group,and MI+GDF11 group.The protective effect of GDF11 on myocardial infarction and its effect on macrophage polarization were verified by echocardiography,triphenyl tetrazolium chloride staining and immunofluorescence staining of heart tissue.In vitro,based on the RAW264.7 cell line,the effect of GDF11 in promoting macrophage polarization toward the M2 type by inhibiting the Notch1 Signaling pathway was validated by qRT-PCR,Western blot,and flow cytometry.Results:We found that GDF11 was significantly downregulated in the cardiac tissue of MI mice.And GDF11 supplementation can improve the cardiac function.Moreover,GDF11 could reduce the proportion of M1 macrophages and increase the accumulation of M2 macrophages in the heart tissue of MI mice.Furthermore,the cardioprotective effect of GDF11 on MI mice was weakened after macrophage clearance.At the cellular level,application of GDF11 could inhibit the expression of M1 macrophage(classically activated macrophage)markers iNOS,interleukin(IL)-1β,and IL-6 in a dose-dependent manner.In contrast,GDF11 significantly increased the level of M2 macrophage markers including IL-10,CD206,arginase 1(Arg1),and vascular endothelial growth factor(VEGF).Interestingly,GDF11 could promote M1 macrophages polarizing to M2 macrophages.At the molecular level,GDF11 significantly down-regulated the Notch1 signaling pathway,the activation of which has been demonstrated to promote M1 polarization in macrophages.Conclusions:GDF11 promoted macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway.展开更多
Mechanical stimulation is the key physical factor in cell environment.Mechanotransduction acts as a fundamental regulator of cell behavior,regulating cell proliferation,differentiation,apoptosis,and exhibiting specifi...Mechanical stimulation is the key physical factor in cell environment.Mechanotransduction acts as a fundamental regulator of cell behavior,regulating cell proliferation,differentiation,apoptosis,and exhibiting specific signature alterations during the pathological process.As research continues,the role of epigenetic science in mechanotransduction is attracting attention.However,the molecular mechanism of the synergistic effect between mechanotransduction and epigenetics in physiological and pathological processes has not been clarified.We focus on how histone modifications,as important components of epigenetics,are coordinated with multiple signaling pathways to control cell fate and disease progression.Specifically,we propose that histone modifications can form regulatory feedback loops with signaling pathways,that is,histone modifications can not only serve as downstream regulators of signaling pathways for target gene transcription but also provide feedback to regulate signaling pathways.Mechanotransduction and epigenetic changes could be potential markers and therapeutic targets in clinical practice.展开更多
Renal dysfunction is a common side-effect of chemotherapeutic agents in patients with hematopathy. Although broadly used, glomerular filtration rate(GFR) estimation equations were not fully validated in this specific ...Renal dysfunction is a common side-effect of chemotherapeutic agents in patients with hematopathy. Although broadly used, glomerular filtration rate(GFR) estimation equations were not fully validated in this specific population. Thus, this study was designed to further assess the accuracy of various GFR equations, including the newly 2012 CKD-EPI equations. Referring to ^(99m)Tc-DTPA clearance method, three Scr-based(MDRD, Peking, and CKD-EPI_(Scr)), three Scys C-based(Steven 1, Steven 2, and CKD-EPI_(Scys C)), and three Scr-Scys C combination based(Ma, Steven 3, and CKD-EPI_(Scr-Scys C)) equations were included. Bias, P_(30), and misclassification rate were applied to compare the applicability of the selected equations. A total of 180 Chinese hematological patients were enrolled.Mean bias, absolute mean bias, P_(30), misclassification rate and Bland-Altman plots of the CKD-EPI_(Scr-Scys C) equation were 7.90 mL/minute/1.73 m^2, 17.77 mL/minute/1.73 m^2, 73.3%, 38% and 79.7 mL/minute/1.73 m^2, respectively.CKD-EPI_(Scr-Scys C) predicted the most precise eGFR both in lymphoma and leukemia subgroups. Additionally, CKDEPI_(Scys C) equation in the rGFR■90 mL/minute/1.73 m^2 subgroup and Steven 2 equation in the rGFR<90 mL/minute/1.73 m^2 subgroup provided more accurate estimates in each subgroup. The CKD-EPI_(Scr-Scys C) equation could be recommended to monitor kidney function in hematopathy patients. The accuracy of GFR equations may be closely related with GFR level and kidney function markers, but not the primary cause of hematopathy.展开更多
The dysbiosis of microbiome may have negative effects on a host phenotype.The microbes related to the host phenotype are regarded as microbial association signals.Recently,statistical methods based on microbiome-pheno...The dysbiosis of microbiome may have negative effects on a host phenotype.The microbes related to the host phenotype are regarded as microbial association signals.Recently,statistical methods based on microbiome-phenotype association tests have been extensively developed to detect these association signals.However,the currently available methods do not perform well to detect microbial association signals when dealing with diverse sparsity levels(i.e.,sparse,low sparse,non-sparse).Actually,the real association patterns related to different host phenotypes are not unique.Here,we propose a powerful and adaptive microbiome-based association test to detect microbial association signals with diverse sparsity levels,designated as MiATDS.In particular,we define probability degree to measure the associations between microbes and the host phenotype and introduce the adaptive weighted sum of powered score tests by considering both probability degree and phylogenetic information.We design numerous simulation experiments for the task of detecting association signals with diverse sparsity levels to prove the performance of the method.We find that type I error rates can be well-controlled and MiATDS shows superior efficiency on the power.By applying to real data analysis,MiATDS displays reliable practicability too.The R package is available at https://github.com/XiaoyunHuang33/MiATDS.展开更多
基金supported by the Leibniz-Forschungsinstitut für Molekulare Pharmakologie(FMP)and the Deutsche Forschungsgemeinschaft(DFG,German Research Foun-dation)under RTG 2473 Bioactive Peptides(392923329)A.F.K.and H.S.under Germany’s Excellence Strategy-EXC 2008/1(UniSysCat,390540038)to C.J.S.and H.S.+2 种基金the National Natural Science Foundation of China(U2006203)to B.-G.W.X.-L.Lsupport from the Taishan Scholars Program(tsqn202306366,China).A.N.-Vthanks National Council for Scien-tific and Technological Development(CNPq)for a research fellowship(309873/2023-1).
文摘Although anisotropic NMR spectroscopy has emerged as a powerful method for determining the relative configuration of complex natural products,major challenges persist with structurally flexible molecules.In this study,we conducted a system-atic comparative analysis of stereochemical elucidation,combining anisotropic NMR spectroscopy and density functional theory(DFT)calculations on spiroepicoccin B(1)and epicoccin V(2),which were characterized as thiodiketopiperazine marine natural products isolated from the deep-sea-derived fungus Epicoccum nigrum SD-388.For the flexible compound 2,we compared various conformational sampling approaches,including an assessment of the quality of relative energies within the obtained ensembles.We demonstrated the critical role of dispersion correction within DFT computations to precisely account for weak non-bonded intramolecular interactions.By integrating anisotropic NMR analysis,chemical shifts,elec-tronic circular dichroism,and DFT computations,we determined the absolute configurations and conformational ensembles for 1 and 2,respectively,highlighting the significance of the intramolecular methyl-πinteraction in stabilizing one of the conformers.Our study introduces new strategies to address conformational flexibility in the stereochemical elucidation of challenging organic molecules.
基金supported by the Fundamental Research Funds for the Central Universities(2021ZY89)the National Natural Science Foundation of China(32201258 and 32271652)+4 种基金Research Service Project on the Effects of Extreme Climate on Biodiversity and Conservation Strategies in Mentougou District(2024HXFWBH-XJL-02)the Fang Jingyun Ecological Study Studio of Yunnan Province(China)the State Scholarship Fund of China(2011811457)support to the Xingdian Scholar Fund of Yunnan Provincethe Double Top University Fund of Yunnan University.
文摘Although numerous studies have proposed explanations for the specific and relative effects of stand structure,plant diversity,and environmental conditions on carbon(C)storage in forest ecosystems,understanding how these factors collectively affect C storage in different community layers(trees,shrubs,and herbs)and forest types(mixed,broad-leaved(E),broad-leaved(M),and coniferous forest)continues to pose challenges.To address this,we used structural equation models to quantify the influence of biotic factors(mean DBH,mean height,maximum height,stem density,and basal area)and abiotic factors(elevation and canopy openness),as well as metrics of species diversity(Shannon–Wiener index,Simpson index,and Pielou’s evenness)in various forest types.Our analysis revealed the critical roles of forest types and elevation in explaining a substantial portion of variability in C storage in the overstory layer,with a moderate influence of stand factors(mean DBH and basal area)and a slightly negative impact of tree species diversity(Shannon–Wiener index).Notably,forest height emerged as the primary predictor of C storage in the herb layer.Regression relationships further highlighted the significant contribution of tree species diversity to mean height,understory C storage,and branch biomass within the forest ecosystem.Our insights into tree species diversity,derived from structural equation modeling of C storage in the overstory,suggest that the effects of tree species diversity may be influenced by stem biomass in statistical reasoning within temperate forests.Further research should also integrate tree species diversity with tree components biomass,forest mean height,understory C,and canopy openness to understand complex relationships and maintain healthy and sustainable ecosystems in the face of global climate challenges.
基金supported by the National Natural Science Foundation of China (No.U1960202).
文摘The machine learning models of multiple linear regression(MLR),support vector regression(SVR),and extreme learning ma-chine(ELM)and the proposed ELM models of online sequential ELM(OS-ELM)and OS-ELM with forgetting mechanism(FOS-ELM)are applied in the prediction of the lime utilization ratio of dephosphorization in the basic oxygen furnace steelmaking process.The ELM model exhibites the best performance compared with the models of MLR and SVR.OS-ELM and FOS-ELM are applied for sequential learning and model updating.The optimal number of samples in validity term of the FOS-ELM model is determined to be 1500,with the smallest population mean absolute relative error(MARE)value of 0.058226 for the population.The variable importance analysis reveals lime weight,initial P content,and hot metal weight as the most important variables for the lime utilization ratio.The lime utilization ratio increases with the decrease in lime weight and the increases in the initial P content and hot metal weight.A prediction system based on FOS-ELM is applied in actual industrial production for one month.The hit ratios of the predicted lime utilization ratio in the error ranges of±1%,±3%,and±5%are 61.16%,90.63%,and 94.11%,respectively.The coefficient of determination,MARE,and root mean square error are 0.8670,0.06823,and 1.4265,respectively.The system exhibits desirable performance for applications in actual industrial pro-duction.
基金support from the National Natural Science Foundation of China (No. U1960202)the Opening Foundation from Shanghai Engineering Research Center of Hot Manufacturing, China (No. 18DZ2253400)。
文摘This work focuses on the influence of Al content on the precipitation of nanoprecipitates,growth of prior austenite grains(PAGs),and impact toughness in simulated coarse-grained heat-affected zones (CGHAZs) of two experimental shipbuilding steels after being subjected to high-heat input welding at 400 kJ·cm^(-1).The base metals (BMs) of both steels contained three types of precipitates Type Ⅰ:cubic (Ti,Nb)(C,N),Type Ⅱ:precipitate with cubic (Ti,Nb)(C,N) core and Nb-rich cap,and Type Ⅲ:ellipsoidal Nb-rich precipitate.In the BM of 60Al and 160Al steels,the number densities of the precipitates were 11.37×10^(5) and 13.88×10^(5) mm^(-2),respectively The 60Al and 160Al steel contained 38.12% and 6.39% Type Ⅲ precipitates,respectively.The difference in the content of Type Ⅲ precipitates in the 60Al steel reduced the pinning effect at the elevated temperature of the CGHAZ,which facilitated the growth of PAGs The average PAG sizes in the CGHAZ of the 60Al and 160Al steels were 189.73 and 174.7μm,respectively.In the 60Al steel,the low lattice mismatch among Cu_(2)S,TiN,and γ-Al_(2)O_(3)facilitated the precipitation of Cu_(2)S and TiN onto γ-Al_(2)O_(3)during welding,which decreased the number density of independently precipitated (Ti,Nb)(C,N) particles but increased that of γ-Al_(2)O_(3)–Ti N–Cu_(2)S particles.Thus abnormally large PAGs formed in the CGHAZ of the 60Al steel,and they reached a maximum size of 1 mm.These PAGs greatly reduced the microstructural homogeneity and consequently decreased the impact toughness from 134 (0.016wt%Al) to 54 J (0.006wt%Al)at-40℃.
文摘BACKGROUND Colorectal polyps are precancerous diseases of colorectal cancer.Early detection and resection of colorectal polyps can effectively reduce the mortality of colorectal cancer.Endoscopic mucosal resection(EMR)is a common polypectomy proce-dure in clinical practice,but it has a high postoperative recurrence rate.Currently,there is no predictive model for the recurrence of colorectal polyps after EMR.AIM To construct and validate a machine learning(ML)model for predicting the risk of colorectal polyp recurrence one year after EMR.METHODS This study retrospectively collected data from 1694 patients at three medical centers in Xuzhou.Additionally,a total of 166 patients were collected to form a prospective validation set.Feature variable screening was conducted using uni-variate and multivariate logistic regression analyses,and five ML algorithms were used to construct the predictive models.The optimal models were evaluated based on different performance metrics.Decision curve analysis(DCA)and SHapley Additive exPlanation(SHAP)analysis were performed to assess clinical applicability and predictor importance.RESULTS Multivariate logistic regression analysis identified 8 independent risk factors for colorectal polyp recurrence one year after EMR(P<0.05).Among the models,eXtreme Gradient Boosting(XGBoost)demonstrated the highest area under the curve(AUC)in the training set,internal validation set,and prospective validation set,with AUCs of 0.909(95%CI:0.89-0.92),0.921(95%CI:0.90-0.94),and 0.963(95%CI:0.94-0.99),respectively.DCA indicated favorable clinical utility for the XGBoost model.SHAP analysis identified smoking history,family history,and age as the top three most important predictors in the model.CONCLUSION The XGBoost model has the best predictive performance and can assist clinicians in providing individualized colonoscopy follow-up recommendations.
基金supported by the National Key Research and Development Program of China,Grant Number:2021YFF0502900,2019YFC1604604National Natural Science Foundation of China,Grant Number:62075013,62027824.
文摘Tumor vaccine therapy offers significant advantages over conventional treatments,including reduced toxic side effects.However,it currently functions primarily as an adjuvant treatment modality in clinical oncology due to limitations in tumor antigen selection and delivery methods.Tumor vaccines often fail to elicit a sufficiently robust immune response against progressive tumors,thereby limiting their clinical efficacy.In this study,we developed a nanoparticle-based tumor vaccine,OVA@HA-PEI,utilizing ovalbumin(OVA)as the presenting antigen and hyaluronic acid(HA)and polyethyleneimine(PEI)as adjuvants and carriers.This formulation significantly enhanced the proliferation of immune cells and cytokines,such as CD3,CD8,interferon-,and tumor necrosis factor-,in vivo,effectively activating an immune response against B16–F10 tumors.In vivofluorescenceflow cytometry(IVFC)has already become an effective method for monitoring circulating tumor cells(CTCs)due to its direct,noninvasive,and long-term detection capabilities.Our study utilized a laboratory-constructed IVFC system to monitor the immune processes induced by the OVA@HA-PEI tumor vaccine and an anti-programmed death-1(PD-1)antibody.The results demonstrated that the combined treatment of OVA@HA-PEI and anti-PD-1 antibody significantly improved the survival time of mice compared to anti-PD-1 antibody treatment alone.Additionally,this combination therapy substantially reduced the number of CTCs in vivo,increased the clearance rate of CTCs by the immune system,and slowed tumor progression.Thesefindings greatly enhance the clinical application prospects of IVFC and tumor vaccines.
基金This work was supported in part by the National Natural Science Foundation of China(82370417,81970320,82270273)the Certificate of China Postdoctoral Science Foundation Grant(2021M693826)+1 种基金the postdoctoral funding from Heilongjiang Province(21042230046)the Hai Yan Youth Fund from Harbin Medical University Cancer Hospital(JJQN2021-09).
文摘Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.
基金financially supported by the National Natural Science Foundation of China (No.U1960202)。
文摘At low basicity and low temperature, the dephosphorization behavior and phosphorus distribution ratio(LP) between slag and molten steel in the double slag and remaining slag process were studied with a 180 t basic oxygen furnace industrial experiment.The dephosphorization slags with different basicities were quantitatively analyzed.At the lower basicity range of 0.9–2.59, both LP and dephosphorization ratio were increased as the basicity of dephosphorization slag increased.Dephosphorization slag consisted of dark gray P-rich, light gray liquid slag,and white Fe-rich phases.With increasing basicity, not only did the morphologies of different phases in the dephosphorization slag change greatly, but the area fractions and P2O5 content of the P-rich phase also increased.The transfer route of P during dephosphorization can be deduced as hot metal → liquid slag phase + Fe-rich phase → P-rich phase.
基金the National Natural Science Foundation of China(Nos.21878227,21276186)for the financial support。
文摘RuPt/AC bimetallic catalysts were pre pared by two-step incipient impregnation method and evaluated in the hydrogenation of phthalates.According to the characterization results,well dispersed Ru Pt bimetallic nanoparticles were formed on the catalyst,and the strong interaction between the two metals resulted in the formation of RuPt alloy.It was found that Ru can donate electrons to Pt on RuPt alloy nanoparticles,leading to the formation of electron-deficient Ru which significantly promotes the hydrogenation rate of dioctyl phthalate and improves the selectivity of dioctyl di-2-ethylhexylcyclohexane-1,4-dicarboxylate by accelerating the further hydrogenation of intermediate products.The bimetallic RuPt catalyst also presented excellent stability and versatility in the hydrogenation of phthalates,demonstrating its prospective future in the hydrogenation of aromatic ring contained compounds.
基金the Fundamental Research Funds for the Central Universities(BLX201802)National Natural Science Foundation of China(31870430)the National Key Research and Development Program of China(#2017YFC0503901).
文摘Background:Metabolic scaling theory(MST)is still in debate because observed allometric exponents often deviate from MST predictions,and can change significantly depending on environment,phylogeny,and disturbance.We assembled published scaling exponents from literatures for three allometric relationships linked to biomass allocation:leaf biomassdiameter(LD),stem biomassdiameter(SD),and root biomassdiameter(RD).We used data from natural forests and plantations across China to test the following hypotheses:1)the allometric relationships of trees support the predictions of MST on a broad scale;2)the observed deviations from MST predictions are caused by climate,biotic factors,and/or phylogeny;3)abiotic and biotic factors influence allometric relationships in plantations and natural forests differently,and different allometric relationships(i.e.LD,SD,and RD)are affected differently.We related these scaling exponents to geographic climate gradient,successional stage,stand density,leaf form and phenology,and phylogeny.We used mixedeffect models to examine the major factors affecting tree allometries.Results:In natural forests,SD and RD scaling exponents were consistent with MST predictions in primary forests,but were significantly lower in secondary forests.Both SD and RD scaling exponents in plantations had a medium value that fell between those of the secondary and primary forests,despite plantations being similar in species characteristics and age to secondary forests.The SD and RD exponents were significantly affected by factors that are not yet considered in MST,including winter coldness which explained 2.76%–3.24%of variations,successional stage(7.91%–8.20%of variations),density(a surrogate for competition,5.86%–8.54%of variations),and especially phylogeny(45.86%–56.64%of variations explained).However,the LD scaling exponents conformed to MST predictions in primary,secondary,and plantation forests,and was not strongly explained by most factors.Conclusion:MST is only applicable to primary(steadystate)forests,and climate,biotic factors and phylogeny are causes of the observed deviations of allometric relationships from MST predictions.Forest management practices in plantations have a strong influence on tree allometries.LD allometry is more strongly controlled by biophysical constraints than SD and RD allometries,however,the mechanisms behind this difference still need further examinations.
基金the National Natural Science Foundation of China(21773056 and 21703056)the Key Science and Technology Program of Henan Province(212102210608 and 202102110289)the Young Backbone Teacher Program of Young Backbone Teacher Program of Henan University of Technology(0503/21420046 and 0503/21420110)。
文摘Sulfonic acid functionalized mesoporous SBA-15 was prepared using the grafting method.The structure and acid properties were comprehensively characterized using multi-nuclear and quantitative probe molecule solid-state NMR(SSNMR),together with powder X-ray diffraction(XRD),scanning electron microscope(SEM),transmission electron microscopy(TEM),N2 adsorption-desorption techniques.Its catalytic performance in the conversion of fructose to 5-hydroxymethylfurfural(HMF)in dimethyl sulfoxide(DMSO)was studied.Catalyst dosage,reaction time,reaction temperature and solvent effect have been investigated.A high yield of HMF up to 93%was obtained at a relatively low temperature of 373 K for 180 min.The Brønsted acid of SBA-15_SO3H together with the solvent DMSO was found to synergistically catalyze the reaction.The catalyst preserved most of its activity after five times reuse and the catalytic activity can be recovered by H2O2 process.
基金This work was supported by the National Natural Science Foundation of China(81970320 and 82003749).
文摘Background:Myocardial infarctions(MI)is a major threat to human health especially in people exposed to cold environment.The polarization of macrophages towards different functional phenotypes(M1 macrophages and M2 macrophages)is closely related to MI repairment.The growth differentiation factor 11(GDF11)has been reported to play a momentous role in inflammatory associated diseases.In this study,we examined the regulatory role of GDF11 in macrophage polarization and elucidated the underlying mechanisms in MI.Methods:In vivo,the mice model of MI was induced by permanent ligation of the left anterior descending coronary artery(LAD),and mice were randomly divided into the sham group,MI group,and MI+GDF11 group.The protective effect of GDF11 on myocardial infarction and its effect on macrophage polarization were verified by echocardiography,triphenyl tetrazolium chloride staining and immunofluorescence staining of heart tissue.In vitro,based on the RAW264.7 cell line,the effect of GDF11 in promoting macrophage polarization toward the M2 type by inhibiting the Notch1 Signaling pathway was validated by qRT-PCR,Western blot,and flow cytometry.Results:We found that GDF11 was significantly downregulated in the cardiac tissue of MI mice.And GDF11 supplementation can improve the cardiac function.Moreover,GDF11 could reduce the proportion of M1 macrophages and increase the accumulation of M2 macrophages in the heart tissue of MI mice.Furthermore,the cardioprotective effect of GDF11 on MI mice was weakened after macrophage clearance.At the cellular level,application of GDF11 could inhibit the expression of M1 macrophage(classically activated macrophage)markers iNOS,interleukin(IL)-1β,and IL-6 in a dose-dependent manner.In contrast,GDF11 significantly increased the level of M2 macrophage markers including IL-10,CD206,arginase 1(Arg1),and vascular endothelial growth factor(VEGF).Interestingly,GDF11 could promote M1 macrophages polarizing to M2 macrophages.At the molecular level,GDF11 significantly down-regulated the Notch1 signaling pathway,the activation of which has been demonstrated to promote M1 polarization in macrophages.Conclusions:GDF11 promoted macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway.
基金the Department of Science and Technology of Jilin Province,China(No.20230101163JC and No.20210509003RQ)。
文摘Mechanical stimulation is the key physical factor in cell environment.Mechanotransduction acts as a fundamental regulator of cell behavior,regulating cell proliferation,differentiation,apoptosis,and exhibiting specific signature alterations during the pathological process.As research continues,the role of epigenetic science in mechanotransduction is attracting attention.However,the molecular mechanism of the synergistic effect between mechanotransduction and epigenetics in physiological and pathological processes has not been clarified.We focus on how histone modifications,as important components of epigenetics,are coordinated with multiple signaling pathways to control cell fate and disease progression.Specifically,we propose that histone modifications can form regulatory feedback loops with signaling pathways,that is,histone modifications can not only serve as downstream regulators of signaling pathways for target gene transcription but also provide feedback to regulate signaling pathways.Mechanotransduction and epigenetic changes could be potential markers and therapeutic targets in clinical practice.
基金supported by the grants from the Major State Basic Research Development Program of China 2013CB530803the National Natural Science Foundation of China H0511-81370843 and H051181670677+3 种基金Chinese Society of Nephrology(15020020590)the Innovation of Science and Technology Achievement Transformation Fund of Jiangsu Province BL2012066the Chinese Medical Association of Clinical Medicine Research Special Funds 15020020590a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions JX10231801
文摘Renal dysfunction is a common side-effect of chemotherapeutic agents in patients with hematopathy. Although broadly used, glomerular filtration rate(GFR) estimation equations were not fully validated in this specific population. Thus, this study was designed to further assess the accuracy of various GFR equations, including the newly 2012 CKD-EPI equations. Referring to ^(99m)Tc-DTPA clearance method, three Scr-based(MDRD, Peking, and CKD-EPI_(Scr)), three Scys C-based(Steven 1, Steven 2, and CKD-EPI_(Scys C)), and three Scr-Scys C combination based(Ma, Steven 3, and CKD-EPI_(Scr-Scys C)) equations were included. Bias, P_(30), and misclassification rate were applied to compare the applicability of the selected equations. A total of 180 Chinese hematological patients were enrolled.Mean bias, absolute mean bias, P_(30), misclassification rate and Bland-Altman plots of the CKD-EPI_(Scr-Scys C) equation were 7.90 mL/minute/1.73 m^2, 17.77 mL/minute/1.73 m^2, 73.3%, 38% and 79.7 mL/minute/1.73 m^2, respectively.CKD-EPI_(Scr-Scys C) predicted the most precise eGFR both in lymphoma and leukemia subgroups. Additionally, CKDEPI_(Scys C) equation in the rGFR■90 mL/minute/1.73 m^2 subgroup and Steven 2 equation in the rGFR<90 mL/minute/1.73 m^2 subgroup provided more accurate estimates in each subgroup. The CKD-EPI_(Scr-Scys C) equation could be recommended to monitor kidney function in hematopathy patients. The accuracy of GFR equations may be closely related with GFR level and kidney function markers, but not the primary cause of hematopathy.
基金supported by the National Natural Science Foundation of China(61872157,61932008,61532008)the Key Research and Development Program of Hubei Province(2020BAB017)。
文摘The dysbiosis of microbiome may have negative effects on a host phenotype.The microbes related to the host phenotype are regarded as microbial association signals.Recently,statistical methods based on microbiome-phenotype association tests have been extensively developed to detect these association signals.However,the currently available methods do not perform well to detect microbial association signals when dealing with diverse sparsity levels(i.e.,sparse,low sparse,non-sparse).Actually,the real association patterns related to different host phenotypes are not unique.Here,we propose a powerful and adaptive microbiome-based association test to detect microbial association signals with diverse sparsity levels,designated as MiATDS.In particular,we define probability degree to measure the associations between microbes and the host phenotype and introduce the adaptive weighted sum of powered score tests by considering both probability degree and phylogenetic information.We design numerous simulation experiments for the task of detecting association signals with diverse sparsity levels to prove the performance of the method.We find that type I error rates can be well-controlled and MiATDS shows superior efficiency on the power.By applying to real data analysis,MiATDS displays reliable practicability too.The R package is available at https://github.com/XiaoyunHuang33/MiATDS.
