Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).Ho...Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).However,the detection and screening of transgenic lines remain major bottlenecks,being time-consuming,labor-intensive,and inefficient during transformation and subsequent mutation identification.A simple and efficient visual marker system plays a critical role in addressing these challenges.Recent studies demonstrated that the GmW1 and RUBY reporter systems were used to obtain visual transgenic soybean(Glycine max) plants(Chen L et al.2023;Chen et al.2024).展开更多
Single-atom nanozymes(SAzymes)exhibit exceptional catalytic efficiency due to their maximized atom utilization and precisely modulated metalcarrier interactions,which have attracted significant attention in the biomed...Single-atom nanozymes(SAzymes)exhibit exceptional catalytic efficiency due to their maximized atom utilization and precisely modulated metalcarrier interactions,which have attracted significant attention in the biomedical field.However,stability issues may impede the clinical translation of SAzymes.This review provides a comprehensive overview of the applications of SAzymes in various biomedical fields,including disease diagnosis(e.g.,biosensors and diagnostic imaging),antitumor therapy(e.g.,photothermal therapy,photodynamic therapy,sonodynamic therapy,and immunotherapy),antimicrobial therapy,and anti-oxidative stress therapy.More importantly,the existing challenges of SAzymes are discussed,such as metal atom clustering and active site loss,ligand bond breakage at high temperature,insufficient environment tolerance,biosecurity risks,and limited catalytic long-term stability.Finally,several innovative strategies to address these stability concerns are proposed—synthesis process optimization(space-limited strategy,coordination site design,bimetallic synergistic strategy,defect engineering strategy,atom stripping-capture),surface modification,and dynamic responsive design—that collectively pave the way for robust,clinically viable SAzymes.展开更多
Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cupropt...Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis,a regulated form of cell death triggered by copper accumulation.The mechanisms underlying copper homeostasis are detailed,including dietary absorption,systemic distribution,and intracellular utilization.Key transporters,such as copper transporter 1(CTR1)and ATPase copper transporting alpha/b(ATP7A/B),are highlighted.Cancer cells often exhibit elevated copper levels,supporting proliferation and metastasis through pro-tumorigenic pathways.Recent studies have shown that disrupting copper homeostasis can induce cuproptosis,which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis.Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors,enhancing therapeutic efficacy through synergistic effects with reactive oxygen species(ROS)generation and immunomodulation.However,the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators.Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance.This review provides a comprehensive overview of copper metabolism in cancer,emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.展开更多
Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,ven...Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,venetoclax plus azacitidine(VEN-AZA)or intensive chemotherapy(IC)]on post-transplant outcomes remains inconclusive.This multicenter,retrospective study compared the post-transplant outcomes between patients receiving VEN-AZA and those receiving IC before allo-HSCT.Methods:This study was based on the transplant database of TROPHY group.Consecutive adverse-risk AML patients receiving allo-HSCT from January 2021 to June 2023 were screened in five Chinese transplant centers.Patients were categorized into VEN-AZA group if they received venetoclax combined with azacitidine as first-line therapy followed by allo-HSCT.Patients who received first-line therapy consisting of a mainstay treatment of cytarabine and anthracycline followed by allo-HSCT were categorized into IC group.Results:In the total cohort,the 3-year probabilities of overall survival,leukemia-free survival,and event-free survival were better in the IC group than VEN-AZA group,particularly for patients with ASXL1 mutations or SF3B1 mutations.However,the survival of the VEN-AZA group was not superior to that of IC group in patients aged≥55 years or those with the hematopoietic cell transplantation-comorbidity index scores≥1 before allo-HSCT.After propensity score matching(median age:VEN-AZA group:57 years;IC group:55 years),only the probability of overall survival for the IC group was better than that of VEN-AZA group(93.6%vs.78.0%,P=0.034)at the 1-year follow-up;however,all of the other clinical outcomes were comparable between the VEN-AZA and IC groups.The TP53 mutation was independently associated with post-transplant relapse and survival.Conclusions:Our results suggest that IC remains the cornerstone of therapy,whereas VEN-AZA may also be used in younger patients and medically fit patients with adverse-risk AML who are receiving allo-HSCT in CR1.展开更多
Hydroisomerization of n-alkanes plays an important role in fuel and lubricants processing.Bifunctional catalysts with ultralow platinum loading have recently been reported successively for hydroisomerisation.Herein,th...Hydroisomerization of n-alkanes plays an important role in fuel and lubricants processing.Bifunctional catalysts with ultralow platinum loading have recently been reported successively for hydroisomerisation.Herein,the catalysts were prepared successfully with different methods to improve the catalytic performance.The conversion of 0.01%Pt1@CeOx/SAPO-11 prepared by co-calcination method(0.01%Pt1@CS-c)is 71.4%,25%higher than the other prepared by precipitation method.The turnover frequency per active surface platinum site(TOFPt)of 0.01%Ptl@CS-c is as high as 13115 h^(-1).Revealed by the X-ray photoelectron spectroscopy(XPS)results,the quality of phase boundary/intersurface between ceria and zeolite is found significantly different.The conjunction quality of phase boundary directly affects the spillover rate of intermediate species,which further leads to an apparent activity difference.In addition,the possible role of ceria in the reaction is discussed,rather than just as a carrier for the active metal atoms.展开更多
The integration of artificial intelligence (AI) with high-throughput experimentation (HTE) techniques is revolutionizing catalyst design, addressing challenges in efficiency, cost, and scalability. This review explore...The integration of artificial intelligence (AI) with high-throughput experimentation (HTE) techniques is revolutionizing catalyst design, addressing challenges in efficiency, cost, and scalability. This review explores the synergistic application of AI and HTE, highlighting their role in accelerating catalyst discovery, optimizing reaction parameters, and understanding structure-performance relationships. HTE facilitates the rapid preparation, characterization, and evaluation of diverse catalyst formulations, generating large datasets essential for AI model training. Machine learning algorithms, including regression models, neural networks, and active learning frameworks, analyze these datasets to uncover the underlying relationships between the data, predict performance, and optimize experimental workflows in real-time. Case studies across heterogeneous, homogeneous, and electrocatalysis demonstrate significant advancements, including improved reaction selectivity, enhanced material stability, and shorten discovery cycles. The integration of AI with HTE has significantly accelerated discovery cycles, enabling the optimization of catalyst formulations and reaction conditions. Despite these achievements, challenges remain, including reliance on researcher expertise, real-time adaptability, and the complexity of large-scale data analysis. Addressing these limitations through refined experimental protocols, standardized datasets, and interpretable AI models will unlock the full potential of AI-HTE integration.展开更多
Chiral cyclic amino alcohols with contiguous stereocenters are key building blocks in the synthesis of bioactive molecules and pharmaceuticals.Artificial cascade biocatalysis represents an attractive method for the sy...Chiral cyclic amino alcohols with contiguous stereocenters are key building blocks in the synthesis of bioactive molecules and pharmaceuticals.Artificial cascade biocatalysis represents an attractive method for the synthesis of chiral molecules bearing multiple stereocenters from readily available materials.Here we reported an artificial cascade biocatalysis comprising an epoxide hydrolase,an alcohol dehydrogenase,and a reductive aminase or an amine dehydrogenase.It can be utilized to access all four stereoisomers of 2-aminocyclohexanol with two contiguous stereocenters in high yields(up to 95%)and excellent stereoselectivity(up to 98%de)starting from readily available cyclohexene oxide without isolation of the intermediates.Additionally,the biocatalytic cascade has been successfully extended to the production of structurally diverse 2-(alkylamino)cyclohexanols by replacing ammonia with different organic amines.展开更多
OBJECTIVE:To assess the effect of Traditional Chinese Medicine(TCM)treatment with syndrome differentiation in patients with severe community-acquired pneumonia(CAP).METHODS:A multicenter,randomized,placebocontrolled t...OBJECTIVE:To assess the effect of Traditional Chinese Medicine(TCM)treatment with syndrome differentiation in patients with severe community-acquired pneumonia(CAP).METHODS:A multicenter,randomized,placebocontrolled trial was conducted.Adult patients with severe CAP were randomly allocated to receive conventional medicine treatment(conventional group)or conventional medicine combine with TCM treatment with syndrome differentiation(combination group)underwent a 28-d treatment time.The primary endpoint was treatment failure.Secondary outcomes included time to clinical stability,28-d mortality,90-d mortality,length of hospital stay.RESULTS:A total of 183 patients were included in the intention-to-treat(ITT)population,with 91 allocated to the combination group and 92 to the conventional group.Patients with treatment failure in the combination group(18/91,19.8%)were lower compared with the conventional group(34/92,37.0%).Time to clinical stability was shorter in the combination group(11.8 d)than in the conventional group[17.8 d;HR=2.08,95%CI(1.38,3.14);P=0.001].The 28-d mortality was lower in the combination group(17.6%)than in the conventional group(31.5%).There was no difference in the length of hospital stay between the two groups(P=0.901).Adverse events were evenly distributed between the combination and conventional groups(P=0.837).CONCLUSION:Among patients with severe CAP,TCM treatment with syndrome differentiation reduced treatment failure,time to clinical stability,and the 28-d mortality and the 90-d mortality among patients admitted to the ward,without an increase in complications.展开更多
Background:Breast cancer remains a leading cause of morbidity and mortality among women worldwide,with significant geographic disparities in its impact.While human epidermal growth factor receptor 2(HER2)-targeted the...Background:Breast cancer remains a leading cause of morbidity and mortality among women worldwide,with significant geographic disparities in its impact.While human epidermal growth factor receptor 2(HER2)-targeted therapies,such as trastuzumab,have improved outcomes for HER2-positive breast cancer,challenges like therapy resistance persist,highlighting the need for novel treatments.Recent developments in antibody-drug conjugates(ADCs),particularly disitamab vedotin(RC48),show promising efficacy in targeting both HER2-positive and HER2-low expression tumors,warranting further investigation through real-world studies to assess its broader clinical applicability.Method:This retrospective,multicenter observational study evaluated the real-world efficacy and safety of RC48 in patients with HER2-positive or HER2-low breast cancer across three medical centers in China.Patient demographic characteristics,treatment patterns,sequential use of ADCs,and treatment-related adverse events were recorded and analyzed.Result:The median progression-free survival(mPFS)for the overall population(n 96)was=4.31 months,with HER2-positive patients demonstrating significantly longer mPFS(5.26 months)compared to HER2-low patients(3.45 months;p<0.044),while subgroup analyses revealed no significant differences in mPFS based on=estrogen receptor(ER),progesterone receptor(PR),or hormone receptor(HR)status.Safety data indicated that adverse events were consistent with prior reports,with no new safety concerns identified during the study period.Conclusion:This real-world study demonstrates the efficacy of RC48 in both HER2-positive and HER2-low breast cancer.Notably,combination therapy significantly improved outcomes in HER2-low patients.展开更多
BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is a procedure used for patients with initially unresectable colorectal liver metastases(CRLM).However,the procedure has bee...BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is a procedure used for patients with initially unresectable colorectal liver metastases(CRLM).However,the procedure has been reported to be associated with high morbidity and mortality.Laparoscopic ALPPS has recently been reported as a minimally invasive technique that reduces perioperative risks.AIM To assess the safety and feasibility of full laparoscopic ALPPS in patients with CRLM.METHODS A retrospective analysis was conducted on all consecutive patients with CRLM who underwent full laparoscopic ALPPS at the Sixth Affiliated Hospital of Sun Yat-sen University between March 2021 and July 2024.RESULTS Fifteen patients were included,13 with synchronous liver metastases.Nine patients had more than five liver tumors,with the highest count being 22.The median diameter of the largest lesion was 2.8 cm on preoperative imaging.No extrahepatic metastases were observed.RAS mutations were detected in nine patients,and 14 underwent preoperative chemotherapy.The median increase in future liver remnant volume during the interstage interval was 47.0%.All patients underwent R0 resection.Overall complication rates were 13.3%(stage 1)and 53.3%(stage 2),while major complication rates(Clavien-Dindo≥IIIa)were 13.3%(stage 1)and 33.3%(stage 2).No mortality occurred in either stage.The median hospital stay after stage 2 was 10 days.CONCLUSION Full laparoscopic ALPPS for CRLM is safe and feasible,with the potential for reduced morbidity and mortality,offering radical resection opportunities for patients with initially unresectable CRLM.展开更多
Solar-driven interface evaporation with high solar-to-steam conversion efficiency has shown great potential in seawater desalination.However,due to the influence of latent heat and condensation efficiency,the water yi...Solar-driven interface evaporation with high solar-to-steam conversion efficiency has shown great potential in seawater desalination.However,due to the influence of latent heat and condensation efficiency,the water yield from solar-driven interface evaporation remains insufficient,posing a significant challenge that requires resolution.In this work,we designed a dual-mode high-flux seawater desalination device that combines solar-driven interface evaporation and capacitive desalination.By utilizing coupled desalination materials exhibiting both photothermal conversion and capacitance activity,the device demonstrated photothermal evaporation rates of 1.41 and 0.97 kg m^(-2)h^(-1)for condensate water yield under one-sun irradiation.Additionally,the device exhibited a salt adsorption capacity of up to48 mg g^(-1)and a salt adsorption rate of 2.1 mg g^(-1)min-1.In addition,the salt adsorption capacity increased by approximately 32%under one-sun irradiation.Furthermore,photo-enhanced capacitive desalination performance was explored through numerical simulations and theoretical calculations.Theoretical calculations and characterizations confirmed that the defect energy levels formed by the introduction of sulfur vacancies can effectively widen the light absorption range,improve photothermal conversion performance,and stimulate more photoelectrons to participate in capacitive desalination.Concurrently,the electron distribution state of molybdenum disulfide with sulfur vacancies and surface defect sites contributes to ion/electron transport at the solid-liquid interface.This work provides a novel pathway for integrating solar vapor generation with other low-energy desalination technologies.展开更多
The slow conversion of polyphase in lithium-sulfur(Li-S)batteries not only intensifies the shuttle effect of lithium polysulfides(LiPSs),but also causes the continuous accumulation of inactive sulfur species,resulting...The slow conversion of polyphase in lithium-sulfur(Li-S)batteries not only intensifies the shuttle effect of lithium polysulfides(LiPSs),but also causes the continuous accumulation of inactive sulfur species,resulting in rapid capacity attenuation and sluggish dynamic performance.Herein,the promoting effect of atomic interface stress on sulfur reaction was investigated via CoFe-CoFe_(2)O_(4)heterogeneous nanosheets with a cavity structure.The strain force induced by the in-situ precipitation of Co Fe bimetallic alloy in oxide matrix increased the d-band center,which was conducive to the interaction between catalyst and Li PSs.The sulfur cathode based on this two-dimensional(2D)nanosheet design showed an extremely high capacity of 751 mAh g^(-1)at 4 C.Even with a sulfur loading of 5.55 mg cm^(-2),its area capacity was still as high as 7.15 mAh cm^(-2).Meanwhile,the enhanced stability greatly improved the practical potential of Li-S batteries.展开更多
Background:Stroke is the second leading cause of death and third leading cause of disability worldwide and is the leading cause of death and disability among adults in China,with its incidence rate continuing to rise....Background:Stroke is the second leading cause of death and third leading cause of disability worldwide and is the leading cause of death and disability among adults in China,with its incidence rate continuing to rise.In China,the average age of firsttime stroke patients is 66.4 years,and the intravenous thrombolysis rate using recombinant tissue plasminogen activator within 3 h of onset is only 16%.Given this fact,there is a pressing need for real‐time predictive tools,particularly for elderly individuals at home,that can provide early warnings for potential strokes.Methods:We collected continuous monitoring data from nonintrusive smart beds and multimodal temporal data from electronic medical records at the National Center for Neurological Disorders.The data included smart bed monitoring indicators,laboratory tests,nurse observations,and static data as potential predictors,with stroke as the outcome.We applied feature representation and feature selection techniques and then input the predictors into machine learning models.Additionally,deep learning models were used after preprocessing the irregular temporal data.Finally,we evaluated the performance of the stroke prediction models and assessed the importance of the features.We used continuously updated vital signs and clinical data during hospitalization to generate timely stroke risk alerts during the same period of admission.Results:A total of 37,041 samples were analyzed,of which 7020 patients were diagnosed with stroke.When only the smart bed features were used for prediction,the model achieved an area under the receiver operating characteristic curve(AUROC)of 0.59−0.63,with an accuracy ranging from 60%−65%.Among the four artificial intelligence algorithms,the random forest model demonstrated the best performance.After all the available features were incorporated,the AUROC increased to 0.94,and the accuracy improved to 92%.Conclusions:In this study,the occurrence of stroke was successfully identified by integrating multimodal temporal data from electronic medical records.Noncontact monitoring of respiration and heart rate offers a promising approach for daily stroke surveillance in home‐based populations,particularly for elderly individuals living alone.展开更多
This study investigated the quasi-biweekly oscillation(QBWO)of the South Asian high(SAH)center in midsummer and its possible impact on rainfall in the middle and lower reaches of the Yangtze River Basin(MLYRB),using E...This study investigated the quasi-biweekly oscillation(QBWO)of the South Asian high(SAH)center in midsummer and its possible impact on rainfall in the middle and lower reaches of the Yangtze River Basin(MLYRB),using ERA5 reanalysis data and CPC(Climate Prediction Center)Global Unified Precipitation data from 1979-2023.First,associated with the phase evolution of the QBWO of the SAH center zonally,a general systematic westward propagation of a wave train pattern along the northern margin of the SAH can be identified.Second,energy analysis indicates that this wave train pattern gains energy from the basic flow through both barotropic and baroclinic energy conversion.Compared with barotropic energy conversion,baroclinic energy conversion plays the more important role in the growth,maintenance,and propagation of the wave train pattern associated with the QBWO of the SAH center.Third,the QBWO of the SAH center leads the variation in rainfall in the MLYRB by approximately four days,and might modulate the precipitation in the MLYRB by affecting the coupling of upper-and lower-level circulation anomalies over the MLYRB.The findings of this study suggest that the QBWO of the SAH center could act as potential source of predictability of intraseasonal variation in precipitation in the MLYRB.展开更多
Objective:This study aimed to construct a model that predicts invasive lung cancer using longitudinal radiological features from multiple low-dose computed tomography(LDCT)scans,thereby addressing overdiagnosis in lun...Objective:This study aimed to construct a model that predicts invasive lung cancer using longitudinal radiological features from multiple low-dose computed tomography(LDCT)scans,thereby addressing overdiagnosis in lung cancer screening.Methods:In this retrospective study,628 patients with pulmonary nodules who underwent three LDCT scans followed by surgical resection were categorized into invasive carcinoma(n=155)and non-invasive nodule(n=473)groups on the basis of pathological diagnosis.This derivation aimed to identify risk factors and construct a multivariate logistic model.The predictive performance was externally validated in two independent cohorts(retrospectively designed,n=252;prospectively designed,n=269).The discrimination and calibration of the model were evaluated using area under the curve(AUC),and calibration plots.Decision curve analysis(DCA)was further performed to evaluate the net benefit in practical clinical scenarios.Results:The model,termed multiple CTs-invasive lung cancer(MCT-ILC),incorporated eleven factors encompassing nodule features at baseline and feature variability during follow-up.The standard deviation of diameter variability(SD_(diameter))was the most reliable predictor,with an odds ratio[95% confidence interval(95%CI)of 7.35(5.32-10.16)(P<0.001)].AUCs with 95% CIs for the MCT-ILC model were 0.912(0.864-0.960)and 0.906(0.833-0.979)in the two testing cohorts and were superior to those for the model containing only features at baseline(PD_(elong)=0.002 and 0.021,respectively).For calibration,the Brier scores of the MCT-ILC model were0.091(95% CI:0.064-0.118) and 0.078(95% CI:0.055-0.101)in the two test sets.The decision curve image showed that the MCT-ILC model was the only model that maintained positive net benefits across the entire threshold range.Furthermore,the MCT-ILC model score could classify more than 90% of patients with invasive nodules into the high-risk group.Conclusions:The MCT-ILC model could assess pulmonary nodule invasiveness,potentially mitigating overdiagnosis in lung cancer screening.展开更多
Objective The aim of this study was to investigate the value of the 8th American Joint Committee on Cancer(AJCC)anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for imp...Objective The aim of this study was to investigate the value of the 8th American Joint Committee on Cancer(AJCC)anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for improvement.Methods The clinical and histopathologic data from 16 centers between January 2000 and December 2021 were assessed according to the 8th AJCC anatomic and prognostic stage groups.Kaplan–Meier plots were used to estimate the disease-specific survival(DSS)of the patients.The accuracy of the staging systems was investigated using the Harrell's concordance index(C-index).Results According to the 8th AJCC anatomic and prognostic stage groups,the 5-year DSS rates for patients with stages 0is/a,I,IIA,IIB,IIIA,IIIB,and IV disease were 100%,99%,86%,81%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–IIA)<0.001,p_(IIA–IIB)=0.5,p_(IIB–IIIA)<0.001,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).According to the modified model 1 system,the 5-year DSS rates without survivorship overlap for patients with stages 0is/a,I,II,IIIA,IIIB,and IV disease were 100%,99%,88%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–II)<0.001,p_(II–IIIA)=0.002,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).Similarly,according to the modified model 2 system,the 5-year DSS rates without survivorship overlap for patients with stages 0is/a,I,II,IIIA,IIIB,and IV disease were 100%,99%,86%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–II)<0.001,p_(II–IIIA)=0.008,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).The C-index scores of the simple modified staging systems were not inferior to those of the AJCC anatomic and prognostic stage groups.These results were confirmed by the bootstrap internal validation.Conclusion There is still room for improvement about the 8th AJCC anatomic and prognostic stage groups.The improved models,which are more concise and convenient,have similar prediction accuracy.展开更多
Background:Hepatocellular carcinoma(HCC)remains a significant global health challenge.While firstline treatments with immune checkpoint inhibitors(ICIs)have improved patient outcomes,the selection of effective second-...Background:Hepatocellular carcinoma(HCC)remains a significant global health challenge.While firstline treatments with immune checkpoint inhibitors(ICIs)have improved patient outcomes,the selection of effective second-line therapies remains unclear.This study evaluated the efficacy and safety of regorafenib as a second-line option in advanced HCC patients post-progression on ICI-based therapies.Methods:Advanced HCC patients from eight hospitals in China who received regorafenib after progression on first-line ICI therapies,alone or combined with ICIs were enrolled.Clinical data were collected,and propensity score matching(PSM)was used to ensure comparability between treatment groups.The primary endpoint was overall survival(OS).The secondary endpoints were progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and treatment-related adverse events.The study was registered at www.chictr.org.cn(ChiCTR2400091318).Results:A total of 149 patients were included:113 in the combination therapy group(Rego-ICI group)and 36 in the regorafenib monotherapy group(Rego group).After PSM,the Rego-ICI group showed significantly improved OS[19.0 vs.11.0 months,hazard ratio(HR)=0.426,95%confidence interval(CI):0.235–0.772,P=0.005]and PFS(4.0 vs.3.0 months,HR=0.539,95%CI:0.337–0.863,P=0.010)compared to the Rego group.Differences in ORR and DCR were not statistically significant(ORR:19.4%vs.9.7%,P=0.226;DCR:64.2%vs.48.4%,P=0.139),but the Rego-ICI group showed better disease control.Regorafenib plus ICI improved both OS and PFS with no new safety signals.Conclusions:The combination of ICIs and regorafenib significantly enhances OS in advanced HCC patients post-progression on first-line ICI treatments.These findings support the potential of regorafenib plus ICIs as an effective second-line therapy.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Fluorescent probes based on intramolecular charge transfer(ICT) have obvious advantages for accurate quantitative analysis.To obtain high-performance ratiometric probes requires distinct photophysical properties durin...Fluorescent probes based on intramolecular charge transfer(ICT) have obvious advantages for accurate quantitative analysis.To obtain high-performance ratiometric probes requires distinct photophysical properties during recognition reaction process,which is closely related to their ICT characteristics.1,8-Naphthalimide is known as a typical fluorophore with desirable ICT property when functionalized with an electron-donating moiety at the para-position of the naphthalene chromophore.Although the photophysical properties of para-substituted 1,8-naphthalimide have been well studied,its meta-substituted counterpart has not been fully evaluated since the meta-position is conventionally thought to be weakly conjugated.Herein,combined experimental and theoretical studies are performed which consistently indicate that stronger charge transfer(CT) is exhibited by the meta-amino substituted 1,8-naphthalimide(m-NH_(2)) compared to the para-amino substituted one(p-NH_(2)).The ratiometric response of fluorescence with significant changes in wavelength and intensity upon acetylation(m-NAc and p-NAc) can be attributed to the larger ICT and stronger-NH_(2) vibrations.This observation is further demonstrated by deuterium oxide experiments,viscosity experiments and quantum chemical calculations.The practical application of meta-amino-1,8-naphthalimide ICT-based probes is also confirmed.This research is expected to bring an in-depth understanding of π-conjugated systems with ICT characteristics,and facilitates the design of sensitive ICT fluorescent probes with meta-amino substitution.展开更多
Interplay between topology and magnetism can give rise to exotic properties in topological materials.Two-dimensional bismuth has been extensively studied owing to its topological states with a strong spin-orbit coupli...Interplay between topology and magnetism can give rise to exotic properties in topological materials.Two-dimensional bismuth has been extensively studied owing to its topological states with a strong spin-orbit coupling,and 1T-VTe_(2)monolayer theoretically predicted to host an intrinsic magnetism as experimentally suggested.In this work,we successfully constructed a vertical heterostructure composed of the two-dimensional Bi(110)monolayer and 1T-VTe_(2)monolayer by using molecular beam epitaxy(MBE).Scanning tunneling microscopy(STM)measurements revealed that the growth of Bi preferably occurs along the step edges of the VTe_(2)monolayer,forming a Bi(110)monolayer on top of the VTe_(2)monolayer next to a peripheral Bi bilayer.The Bi(100)/VTe_(2)heterostructure exhibits a specific lattice registry with a well-defined moiréperiodicity.Scanning tunneling spectroscopy(STS)measurements further unveiled an universal suppression in the local density-of-states at the boundary of the Bi(110)/VTe_(2)bilayer.By examining the atomic structures of Bi(110)boundaries,we found this effect does not originate from the previously proposed atomic reconstruction at the step edge of Bi(110),but is likely related to the magnetic properties of the VTe_(2)monolayer.展开更多
基金supported by the Jilin Science and Technology Development Program,China (20240602032RC)the Jilin Agricultural Science and Technology Innovation Project,China (CXGC2024ZD001)+1 种基金the Jilin Agricultural Science and Technology Innovation Project,China (CXGC2024ZY012)the Jilin Province Development and Reform Commission-Project for Improving the Independent Innovation Capacity of Major Grain Crops,China (2024C002)。
文摘Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).However,the detection and screening of transgenic lines remain major bottlenecks,being time-consuming,labor-intensive,and inefficient during transformation and subsequent mutation identification.A simple and efficient visual marker system plays a critical role in addressing these challenges.Recent studies demonstrated that the GmW1 and RUBY reporter systems were used to obtain visual transgenic soybean(Glycine max) plants(Chen L et al.2023;Chen et al.2024).
基金supported by the National Natural Science Foundation of China[82003956]the National Key Research and Development Program of China[No.2022YFA1205802]+2 种基金financially supported by Henan Province Health Science and Technology Innovation Youth Talent Project(YQRC2023013 and YQRC2024013)the Key Project of Medical Science and Technology of Henan Province(SBGJ202302072)the Science and Technology Research Project of Henan Province(252102311236).
文摘Single-atom nanozymes(SAzymes)exhibit exceptional catalytic efficiency due to their maximized atom utilization and precisely modulated metalcarrier interactions,which have attracted significant attention in the biomedical field.However,stability issues may impede the clinical translation of SAzymes.This review provides a comprehensive overview of the applications of SAzymes in various biomedical fields,including disease diagnosis(e.g.,biosensors and diagnostic imaging),antitumor therapy(e.g.,photothermal therapy,photodynamic therapy,sonodynamic therapy,and immunotherapy),antimicrobial therapy,and anti-oxidative stress therapy.More importantly,the existing challenges of SAzymes are discussed,such as metal atom clustering and active site loss,ligand bond breakage at high temperature,insufficient environment tolerance,biosecurity risks,and limited catalytic long-term stability.Finally,several innovative strategies to address these stability concerns are proposed—synthesis process optimization(space-limited strategy,coordination site design,bimetallic synergistic strategy,defect engineering strategy,atom stripping-capture),surface modification,and dynamic responsive design—that collectively pave the way for robust,clinically viable SAzymes.
基金supported by the National Natural Science Foundation of China(Grant Nos.82303206,82372749,and 82072951)Science and Technology Commission of Shanghai Municipality(Grant Nos.20Y11914300 and 22Y21900100)+2 种基金Shanghai Anticancer Association(Grant No.SACAAX202213)Major Research Projects of Taizhou Clinical Medical College(Grant No.TZKY20230308)Natural Science Foundation in University of Jiangsu Province(Grant No.BK20231261).
文摘Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis,a regulated form of cell death triggered by copper accumulation.The mechanisms underlying copper homeostasis are detailed,including dietary absorption,systemic distribution,and intracellular utilization.Key transporters,such as copper transporter 1(CTR1)and ATPase copper transporting alpha/b(ATP7A/B),are highlighted.Cancer cells often exhibit elevated copper levels,supporting proliferation and metastasis through pro-tumorigenic pathways.Recent studies have shown that disrupting copper homeostasis can induce cuproptosis,which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis.Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors,enhancing therapeutic efficacy through synergistic effects with reactive oxygen species(ROS)generation and immunomodulation.However,the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators.Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance.This review provides a comprehensive overview of copper metabolism in cancer,emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.
基金supported by the Beijing Natural Science Foundation(No.Z230016)the National Key Research and Development Program of China(No.2022YFC 2502606)+4 种基金the Major Program of the National Natural Science Foundation of China(No.82293630)the Peking University Medicine Fund for the World’s Leading Discipline or Discipline Cluster Development(No.71003Y3035)the Plan Project of Tongzhou Municipal Science and Technology(No.KJ2024CX045)the National Natural Science Foundation of China(No.82170208)the Fundamental Research Funds for the Central Universities。
文摘Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,venetoclax plus azacitidine(VEN-AZA)or intensive chemotherapy(IC)]on post-transplant outcomes remains inconclusive.This multicenter,retrospective study compared the post-transplant outcomes between patients receiving VEN-AZA and those receiving IC before allo-HSCT.Methods:This study was based on the transplant database of TROPHY group.Consecutive adverse-risk AML patients receiving allo-HSCT from January 2021 to June 2023 were screened in five Chinese transplant centers.Patients were categorized into VEN-AZA group if they received venetoclax combined with azacitidine as first-line therapy followed by allo-HSCT.Patients who received first-line therapy consisting of a mainstay treatment of cytarabine and anthracycline followed by allo-HSCT were categorized into IC group.Results:In the total cohort,the 3-year probabilities of overall survival,leukemia-free survival,and event-free survival were better in the IC group than VEN-AZA group,particularly for patients with ASXL1 mutations or SF3B1 mutations.However,the survival of the VEN-AZA group was not superior to that of IC group in patients aged≥55 years or those with the hematopoietic cell transplantation-comorbidity index scores≥1 before allo-HSCT.After propensity score matching(median age:VEN-AZA group:57 years;IC group:55 years),only the probability of overall survival for the IC group was better than that of VEN-AZA group(93.6%vs.78.0%,P=0.034)at the 1-year follow-up;however,all of the other clinical outcomes were comparable between the VEN-AZA and IC groups.The TP53 mutation was independently associated with post-transplant relapse and survival.Conclusions:Our results suggest that IC remains the cornerstone of therapy,whereas VEN-AZA may also be used in younger patients and medically fit patients with adverse-risk AML who are receiving allo-HSCT in CR1.
基金Project supported by National Natural Science Foundation of China(22078159,U19B2001)。
文摘Hydroisomerization of n-alkanes plays an important role in fuel and lubricants processing.Bifunctional catalysts with ultralow platinum loading have recently been reported successively for hydroisomerisation.Herein,the catalysts were prepared successfully with different methods to improve the catalytic performance.The conversion of 0.01%Pt1@CeOx/SAPO-11 prepared by co-calcination method(0.01%Pt1@CS-c)is 71.4%,25%higher than the other prepared by precipitation method.The turnover frequency per active surface platinum site(TOFPt)of 0.01%Ptl@CS-c is as high as 13115 h^(-1).Revealed by the X-ray photoelectron spectroscopy(XPS)results,the quality of phase boundary/intersurface between ceria and zeolite is found significantly different.The conjunction quality of phase boundary directly affects the spillover rate of intermediate species,which further leads to an apparent activity difference.In addition,the possible role of ceria in the reaction is discussed,rather than just as a carrier for the active metal atoms.
基金supported by the Special Project of National Natural Science Foundation(42341204)the the National Natural Science Foundation of China(W2411009).
文摘The integration of artificial intelligence (AI) with high-throughput experimentation (HTE) techniques is revolutionizing catalyst design, addressing challenges in efficiency, cost, and scalability. This review explores the synergistic application of AI and HTE, highlighting their role in accelerating catalyst discovery, optimizing reaction parameters, and understanding structure-performance relationships. HTE facilitates the rapid preparation, characterization, and evaluation of diverse catalyst formulations, generating large datasets essential for AI model training. Machine learning algorithms, including regression models, neural networks, and active learning frameworks, analyze these datasets to uncover the underlying relationships between the data, predict performance, and optimize experimental workflows in real-time. Case studies across heterogeneous, homogeneous, and electrocatalysis demonstrate significant advancements, including improved reaction selectivity, enhanced material stability, and shorten discovery cycles. The integration of AI with HTE has significantly accelerated discovery cycles, enabling the optimization of catalyst formulations and reaction conditions. Despite these achievements, challenges remain, including reliance on researcher expertise, real-time adaptability, and the complexity of large-scale data analysis. Addressing these limitations through refined experimental protocols, standardized datasets, and interpretable AI models will unlock the full potential of AI-HTE integration.
文摘Chiral cyclic amino alcohols with contiguous stereocenters are key building blocks in the synthesis of bioactive molecules and pharmaceuticals.Artificial cascade biocatalysis represents an attractive method for the synthesis of chiral molecules bearing multiple stereocenters from readily available materials.Here we reported an artificial cascade biocatalysis comprising an epoxide hydrolase,an alcohol dehydrogenase,and a reductive aminase or an amine dehydrogenase.It can be utilized to access all four stereoisomers of 2-aminocyclohexanol with two contiguous stereocenters in high yields(up to 95%)and excellent stereoselectivity(up to 98%de)starting from readily available cyclohexene oxide without isolation of the intermediates.Additionally,the biocatalytic cascade has been successfully extended to the production of structurally diverse 2-(alkylamino)cyclohexanols by replacing ammonia with different organic amines.
基金National Natural Science Foundation of China:Study on the Mechanism of Qingre jiedu Huatan Formula Regulating Macrophage Mitochondrial Autophagy/NLR family pyrin domain containing 3 Inflammasome Activation and Intervening intestinal-Lung Bacterial Translocation in the Treatment of Severe Pneumonia(No.82074411)Science and Technology Innovation Team Support Program of Universities in Henan Province:Study on Prevention and Treatment of Respiratory Critical Illness with Traditional Chinese Medicine(No.22IRTSTHN029)Traditional Chinese Medicine Discipline Construction Project of Characteristic Backbone Discipline in Henan Province:Integrated Traditional Chinese and Conventional Medicine in Treatment of Severe Novel Coronavirus Infection:a Randomized Controlled Trial(No.STG-ZYX02-202204)。
文摘OBJECTIVE:To assess the effect of Traditional Chinese Medicine(TCM)treatment with syndrome differentiation in patients with severe community-acquired pneumonia(CAP).METHODS:A multicenter,randomized,placebocontrolled trial was conducted.Adult patients with severe CAP were randomly allocated to receive conventional medicine treatment(conventional group)or conventional medicine combine with TCM treatment with syndrome differentiation(combination group)underwent a 28-d treatment time.The primary endpoint was treatment failure.Secondary outcomes included time to clinical stability,28-d mortality,90-d mortality,length of hospital stay.RESULTS:A total of 183 patients were included in the intention-to-treat(ITT)population,with 91 allocated to the combination group and 92 to the conventional group.Patients with treatment failure in the combination group(18/91,19.8%)were lower compared with the conventional group(34/92,37.0%).Time to clinical stability was shorter in the combination group(11.8 d)than in the conventional group[17.8 d;HR=2.08,95%CI(1.38,3.14);P=0.001].The 28-d mortality was lower in the combination group(17.6%)than in the conventional group(31.5%).There was no difference in the length of hospital stay between the two groups(P=0.901).Adverse events were evenly distributed between the combination and conventional groups(P=0.837).CONCLUSION:Among patients with severe CAP,TCM treatment with syndrome differentiation reduced treatment failure,time to clinical stability,and the 28-d mortality and the 90-d mortality among patients admitted to the ward,without an increase in complications.
基金funded by the medical and health category of the Science and Technology Project of Shantou(No.230509116495542,Wu Haoming)National Natural Science Foundation of China(NSFC)Cultivation Project of the Cancer Hospital of Shantou University Medical College(No.2024GP002,Wu Haoming)National Natural Science Foundation of China(82203130,Ye Feng).
文摘Background:Breast cancer remains a leading cause of morbidity and mortality among women worldwide,with significant geographic disparities in its impact.While human epidermal growth factor receptor 2(HER2)-targeted therapies,such as trastuzumab,have improved outcomes for HER2-positive breast cancer,challenges like therapy resistance persist,highlighting the need for novel treatments.Recent developments in antibody-drug conjugates(ADCs),particularly disitamab vedotin(RC48),show promising efficacy in targeting both HER2-positive and HER2-low expression tumors,warranting further investigation through real-world studies to assess its broader clinical applicability.Method:This retrospective,multicenter observational study evaluated the real-world efficacy and safety of RC48 in patients with HER2-positive or HER2-low breast cancer across three medical centers in China.Patient demographic characteristics,treatment patterns,sequential use of ADCs,and treatment-related adverse events were recorded and analyzed.Result:The median progression-free survival(mPFS)for the overall population(n 96)was=4.31 months,with HER2-positive patients demonstrating significantly longer mPFS(5.26 months)compared to HER2-low patients(3.45 months;p<0.044),while subgroup analyses revealed no significant differences in mPFS based on=estrogen receptor(ER),progesterone receptor(PR),or hormone receptor(HR)status.Safety data indicated that adverse events were consistent with prior reports,with no new safety concerns identified during the study period.Conclusion:This real-world study demonstrates the efficacy of RC48 in both HER2-positive and HER2-low breast cancer.Notably,combination therapy significantly improved outcomes in HER2-low patients.
基金Supported by Natural Science Foundation of Guangdong Province of China,No.2024A1515012862.
文摘BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is a procedure used for patients with initially unresectable colorectal liver metastases(CRLM).However,the procedure has been reported to be associated with high morbidity and mortality.Laparoscopic ALPPS has recently been reported as a minimally invasive technique that reduces perioperative risks.AIM To assess the safety and feasibility of full laparoscopic ALPPS in patients with CRLM.METHODS A retrospective analysis was conducted on all consecutive patients with CRLM who underwent full laparoscopic ALPPS at the Sixth Affiliated Hospital of Sun Yat-sen University between March 2021 and July 2024.RESULTS Fifteen patients were included,13 with synchronous liver metastases.Nine patients had more than five liver tumors,with the highest count being 22.The median diameter of the largest lesion was 2.8 cm on preoperative imaging.No extrahepatic metastases were observed.RAS mutations were detected in nine patients,and 14 underwent preoperative chemotherapy.The median increase in future liver remnant volume during the interstage interval was 47.0%.All patients underwent R0 resection.Overall complication rates were 13.3%(stage 1)and 53.3%(stage 2),while major complication rates(Clavien-Dindo≥IIIa)were 13.3%(stage 1)and 33.3%(stage 2).No mortality occurred in either stage.The median hospital stay after stage 2 was 10 days.CONCLUSION Full laparoscopic ALPPS for CRLM is safe and feasible,with the potential for reduced morbidity and mortality,offering radical resection opportunities for patients with initially unresectable CRLM.
基金financially supported by research grants from the Natural Science Foundation of China(52173235,22265010,12204071,62074022)National Key Research and Development Program of China(2022YFB3803300)+2 种基金Youth Talent Support Program of Chongqing(CQYC2021059206)Hainan Province Science and Technology Special Fund(ZDYF2024SHFZ038)Science and Technology Innovation and Improving Project of Army Medical University(No.2021XJS24)。
文摘Solar-driven interface evaporation with high solar-to-steam conversion efficiency has shown great potential in seawater desalination.However,due to the influence of latent heat and condensation efficiency,the water yield from solar-driven interface evaporation remains insufficient,posing a significant challenge that requires resolution.In this work,we designed a dual-mode high-flux seawater desalination device that combines solar-driven interface evaporation and capacitive desalination.By utilizing coupled desalination materials exhibiting both photothermal conversion and capacitance activity,the device demonstrated photothermal evaporation rates of 1.41 and 0.97 kg m^(-2)h^(-1)for condensate water yield under one-sun irradiation.Additionally,the device exhibited a salt adsorption capacity of up to48 mg g^(-1)and a salt adsorption rate of 2.1 mg g^(-1)min-1.In addition,the salt adsorption capacity increased by approximately 32%under one-sun irradiation.Furthermore,photo-enhanced capacitive desalination performance was explored through numerical simulations and theoretical calculations.Theoretical calculations and characterizations confirmed that the defect energy levels formed by the introduction of sulfur vacancies can effectively widen the light absorption range,improve photothermal conversion performance,and stimulate more photoelectrons to participate in capacitive desalination.Concurrently,the electron distribution state of molybdenum disulfide with sulfur vacancies and surface defect sites contributes to ion/electron transport at the solid-liquid interface.This work provides a novel pathway for integrating solar vapor generation with other low-energy desalination technologies.
基金the National Natural Science Foundation of China(No.52207227)the Fundamental Research Funds for the Central Universities(No.0213-14380196)+1 种基金the Science and Technology Project of Nanchang(No.2017-SJSYS-008)the Anhui Absorption Spectroscopy Analysis Instrument Co,Ltd.for XAFS measurements and analysis。
文摘The slow conversion of polyphase in lithium-sulfur(Li-S)batteries not only intensifies the shuttle effect of lithium polysulfides(LiPSs),but also causes the continuous accumulation of inactive sulfur species,resulting in rapid capacity attenuation and sluggish dynamic performance.Herein,the promoting effect of atomic interface stress on sulfur reaction was investigated via CoFe-CoFe_(2)O_(4)heterogeneous nanosheets with a cavity structure.The strain force induced by the in-situ precipitation of Co Fe bimetallic alloy in oxide matrix increased the d-band center,which was conducive to the interaction between catalyst and Li PSs.The sulfur cathode based on this two-dimensional(2D)nanosheet design showed an extremely high capacity of 751 mAh g^(-1)at 4 C.Even with a sulfur loading of 5.55 mg cm^(-2),its area capacity was still as high as 7.15 mAh cm^(-2).Meanwhile,the enhanced stability greatly improved the practical potential of Li-S batteries.
基金supported by the National Natural Science Foundation of China(72204169,82425101,82271516,81801187)Noncommunicable Chronic Diseases‐National Science and Technology Major Project(2023ZD0504800,2023ZD0504801,2023ZD0504802,2023ZD0504803,2023ZD0504804)+2 种基金Beijing Municipal Science&Technology Commission(Z231100004823036)Capital's Funds for Health Improvement and Research(2022‐2‐2045)National Key R&D Program of China(2024YFC3044800,2022YFF1501500,2022YFF1501501,2022YFF1501502,2022YFF1501503,2022YFF1501504,2022YFF1501505).
文摘Background:Stroke is the second leading cause of death and third leading cause of disability worldwide and is the leading cause of death and disability among adults in China,with its incidence rate continuing to rise.In China,the average age of firsttime stroke patients is 66.4 years,and the intravenous thrombolysis rate using recombinant tissue plasminogen activator within 3 h of onset is only 16%.Given this fact,there is a pressing need for real‐time predictive tools,particularly for elderly individuals at home,that can provide early warnings for potential strokes.Methods:We collected continuous monitoring data from nonintrusive smart beds and multimodal temporal data from electronic medical records at the National Center for Neurological Disorders.The data included smart bed monitoring indicators,laboratory tests,nurse observations,and static data as potential predictors,with stroke as the outcome.We applied feature representation and feature selection techniques and then input the predictors into machine learning models.Additionally,deep learning models were used after preprocessing the irregular temporal data.Finally,we evaluated the performance of the stroke prediction models and assessed the importance of the features.We used continuously updated vital signs and clinical data during hospitalization to generate timely stroke risk alerts during the same period of admission.Results:A total of 37,041 samples were analyzed,of which 7020 patients were diagnosed with stroke.When only the smart bed features were used for prediction,the model achieved an area under the receiver operating characteristic curve(AUROC)of 0.59−0.63,with an accuracy ranging from 60%−65%.Among the four artificial intelligence algorithms,the random forest model demonstrated the best performance.After all the available features were incorporated,the AUROC increased to 0.94,and the accuracy improved to 92%.Conclusions:In this study,the occurrence of stroke was successfully identified by integrating multimodal temporal data from electronic medical records.Noncontact monitoring of respiration and heart rate offers a promising approach for daily stroke surveillance in home‐based populations,particularly for elderly individuals living alone.
基金supported jointly by the National Natural Science Foundation of China(Grant No.42105039)the China Postdoctoral Science Foundation(Grant No.2024M753587)+4 种基金the Hubei Provincial Natural Science Foundation and Meteorological Innovation and development Joint Foundation of China(Grant No.2023AFD104)the Shanghai Science and Technology Development Funds(Grant No.24QB2703600)the Open Project Fund of the China Meteorological Administration Basin Heavy Rainfall Key Laboratory(Grant No.2023BHR-Y03)the Basic Research Fund of the Institute of Heavy Rain,China Meteorological Administration,Wuhan(Grant No.202314)the Open Project Fund of the Key Open Laboratory of Hydrometeorology,China Meteorological Administration(Grant No.23SWQXM018)。
文摘This study investigated the quasi-biweekly oscillation(QBWO)of the South Asian high(SAH)center in midsummer and its possible impact on rainfall in the middle and lower reaches of the Yangtze River Basin(MLYRB),using ERA5 reanalysis data and CPC(Climate Prediction Center)Global Unified Precipitation data from 1979-2023.First,associated with the phase evolution of the QBWO of the SAH center zonally,a general systematic westward propagation of a wave train pattern along the northern margin of the SAH can be identified.Second,energy analysis indicates that this wave train pattern gains energy from the basic flow through both barotropic and baroclinic energy conversion.Compared with barotropic energy conversion,baroclinic energy conversion plays the more important role in the growth,maintenance,and propagation of the wave train pattern associated with the QBWO of the SAH center.Third,the QBWO of the SAH center leads the variation in rainfall in the MLYRB by approximately four days,and might modulate the precipitation in the MLYRB by affecting the coupling of upper-and lower-level circulation anomalies over the MLYRB.The findings of this study suggest that the QBWO of the SAH center could act as potential source of predictability of intraseasonal variation in precipitation in the MLYRB.
基金funded by grants from Project supported by the Funds for Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2024ZD0520000,2024ZD0520003)Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2024ZD0524400,2024ZD0524403)+2 种基金National Natural Science Foundation of China(No.82388102)Jiangsu Medical Association Medical Research Project of Health Management,SYH-32099-0119(No.2024023)the Specialized Diseases Clinical Research Fund of Jiangsu Province Hospital(No.DL202411)。
文摘Objective:This study aimed to construct a model that predicts invasive lung cancer using longitudinal radiological features from multiple low-dose computed tomography(LDCT)scans,thereby addressing overdiagnosis in lung cancer screening.Methods:In this retrospective study,628 patients with pulmonary nodules who underwent three LDCT scans followed by surgical resection were categorized into invasive carcinoma(n=155)and non-invasive nodule(n=473)groups on the basis of pathological diagnosis.This derivation aimed to identify risk factors and construct a multivariate logistic model.The predictive performance was externally validated in two independent cohorts(retrospectively designed,n=252;prospectively designed,n=269).The discrimination and calibration of the model were evaluated using area under the curve(AUC),and calibration plots.Decision curve analysis(DCA)was further performed to evaluate the net benefit in practical clinical scenarios.Results:The model,termed multiple CTs-invasive lung cancer(MCT-ILC),incorporated eleven factors encompassing nodule features at baseline and feature variability during follow-up.The standard deviation of diameter variability(SD_(diameter))was the most reliable predictor,with an odds ratio[95% confidence interval(95%CI)of 7.35(5.32-10.16)(P<0.001)].AUCs with 95% CIs for the MCT-ILC model were 0.912(0.864-0.960)and 0.906(0.833-0.979)in the two testing cohorts and were superior to those for the model containing only features at baseline(PD_(elong)=0.002 and 0.021,respectively).For calibration,the Brier scores of the MCT-ILC model were0.091(95% CI:0.064-0.118) and 0.078(95% CI:0.055-0.101)in the two test sets.The decision curve image showed that the MCT-ILC model was the only model that maintained positive net benefits across the entire threshold range.Furthermore,the MCT-ILC model score could classify more than 90% of patients with invasive nodules into the high-risk group.Conclusions:The MCT-ILC model could assess pulmonary nodule invasiveness,potentially mitigating overdiagnosis in lung cancer screening.
基金supported by the Guangdong Province Nature Foundation of China Project (No. 2022A1515012200 to Li Z)Shenzhen Science and Technology Program (No. RCYX20221008093032008 to Li Z)Shenzhen People's Hospital Clinician Scientist Training Program (No. SYWGSJCYJ202405 to Li Z).
文摘Objective The aim of this study was to investigate the value of the 8th American Joint Committee on Cancer(AJCC)anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for improvement.Methods The clinical and histopathologic data from 16 centers between January 2000 and December 2021 were assessed according to the 8th AJCC anatomic and prognostic stage groups.Kaplan–Meier plots were used to estimate the disease-specific survival(DSS)of the patients.The accuracy of the staging systems was investigated using the Harrell's concordance index(C-index).Results According to the 8th AJCC anatomic and prognostic stage groups,the 5-year DSS rates for patients with stages 0is/a,I,IIA,IIB,IIIA,IIIB,and IV disease were 100%,99%,86%,81%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–IIA)<0.001,p_(IIA–IIB)=0.5,p_(IIB–IIIA)<0.001,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).According to the modified model 1 system,the 5-year DSS rates without survivorship overlap for patients with stages 0is/a,I,II,IIIA,IIIB,and IV disease were 100%,99%,88%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–II)<0.001,p_(II–IIIA)=0.002,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).Similarly,according to the modified model 2 system,the 5-year DSS rates without survivorship overlap for patients with stages 0is/a,I,II,IIIA,IIIB,and IV disease were 100%,99%,86%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–II)<0.001,p_(II–IIIA)=0.008,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).The C-index scores of the simple modified staging systems were not inferior to those of the AJCC anatomic and prognostic stage groups.These results were confirmed by the bootstrap internal validation.Conclusion There is still room for improvement about the 8th AJCC anatomic and prognostic stage groups.The improved models,which are more concise and convenient,have similar prediction accuracy.
基金supported by a grant from the Zhongda Hospital Affiliated to Southeast University,Jiangsu Province High-Level Hospital Construction Funds(No.YKK24270)。
文摘Background:Hepatocellular carcinoma(HCC)remains a significant global health challenge.While firstline treatments with immune checkpoint inhibitors(ICIs)have improved patient outcomes,the selection of effective second-line therapies remains unclear.This study evaluated the efficacy and safety of regorafenib as a second-line option in advanced HCC patients post-progression on ICI-based therapies.Methods:Advanced HCC patients from eight hospitals in China who received regorafenib after progression on first-line ICI therapies,alone or combined with ICIs were enrolled.Clinical data were collected,and propensity score matching(PSM)was used to ensure comparability between treatment groups.The primary endpoint was overall survival(OS).The secondary endpoints were progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and treatment-related adverse events.The study was registered at www.chictr.org.cn(ChiCTR2400091318).Results:A total of 149 patients were included:113 in the combination therapy group(Rego-ICI group)and 36 in the regorafenib monotherapy group(Rego group).After PSM,the Rego-ICI group showed significantly improved OS[19.0 vs.11.0 months,hazard ratio(HR)=0.426,95%confidence interval(CI):0.235–0.772,P=0.005]and PFS(4.0 vs.3.0 months,HR=0.539,95%CI:0.337–0.863,P=0.010)compared to the Rego group.Differences in ORR and DCR were not statistically significant(ORR:19.4%vs.9.7%,P=0.226;DCR:64.2%vs.48.4%,P=0.139),but the Rego-ICI group showed better disease control.Regorafenib plus ICI improved both OS and PFS with no new safety signals.Conclusions:The combination of ICIs and regorafenib significantly enhances OS in advanced HCC patients post-progression on first-line ICI treatments.These findings support the potential of regorafenib plus ICIs as an effective second-line therapy.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金financially supported by National Key Research and Development Programs (Nos.2022YFD1700403 and 2023YFD1700303)National Natural Science Foundation of China (Nos.12274128 and 12250003)+2 种基金Shanghai Rising-Star Program (No.21QA1402600)the support of NYU-ECNU Center for Computational Chemistry at NYU Shanghaithe University of Bath and the Open Research Fund of the School of Chemistry and Chemical Engineering,Henan Normal University (No.2020ZD01) for support。
文摘Fluorescent probes based on intramolecular charge transfer(ICT) have obvious advantages for accurate quantitative analysis.To obtain high-performance ratiometric probes requires distinct photophysical properties during recognition reaction process,which is closely related to their ICT characteristics.1,8-Naphthalimide is known as a typical fluorophore with desirable ICT property when functionalized with an electron-donating moiety at the para-position of the naphthalene chromophore.Although the photophysical properties of para-substituted 1,8-naphthalimide have been well studied,its meta-substituted counterpart has not been fully evaluated since the meta-position is conventionally thought to be weakly conjugated.Herein,combined experimental and theoretical studies are performed which consistently indicate that stronger charge transfer(CT) is exhibited by the meta-amino substituted 1,8-naphthalimide(m-NH_(2)) compared to the para-amino substituted one(p-NH_(2)).The ratiometric response of fluorescence with significant changes in wavelength and intensity upon acetylation(m-NAc and p-NAc) can be attributed to the larger ICT and stronger-NH_(2) vibrations.This observation is further demonstrated by deuterium oxide experiments,viscosity experiments and quantum chemical calculations.The practical application of meta-amino-1,8-naphthalimide ICT-based probes is also confirmed.This research is expected to bring an in-depth understanding of π-conjugated systems with ICT characteristics,and facilitates the design of sensitive ICT fluorescent probes with meta-amino substitution.
基金financially supported by the National Key Research and Development Program of China(Grant No.2021YFA1400403)the National Natural Science Foundation of China(Grant Nos.12374183,92165205)+2 种基金the Natural Science Foundation of Jiangsu Province(Grant No.BK20233001)the Innovation Program for Quantum Science and Technology(Grant No.2021ZD0302800)the Fundamental Research Funds for the Central Universities(Grant No.020414380207).
文摘Interplay between topology and magnetism can give rise to exotic properties in topological materials.Two-dimensional bismuth has been extensively studied owing to its topological states with a strong spin-orbit coupling,and 1T-VTe_(2)monolayer theoretically predicted to host an intrinsic magnetism as experimentally suggested.In this work,we successfully constructed a vertical heterostructure composed of the two-dimensional Bi(110)monolayer and 1T-VTe_(2)monolayer by using molecular beam epitaxy(MBE).Scanning tunneling microscopy(STM)measurements revealed that the growth of Bi preferably occurs along the step edges of the VTe_(2)monolayer,forming a Bi(110)monolayer on top of the VTe_(2)monolayer next to a peripheral Bi bilayer.The Bi(100)/VTe_(2)heterostructure exhibits a specific lattice registry with a well-defined moiréperiodicity.Scanning tunneling spectroscopy(STS)measurements further unveiled an universal suppression in the local density-of-states at the boundary of the Bi(110)/VTe_(2)bilayer.By examining the atomic structures of Bi(110)boundaries,we found this effect does not originate from the previously proposed atomic reconstruction at the step edge of Bi(110),but is likely related to the magnetic properties of the VTe_(2)monolayer.
