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
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
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 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
Obesity,a widespread global health issue,is frequently linked to disrupted lipid metabolism,resulting in excessive accumulation of adipose tissue and associated health complications.Acupuncture,a traditional Chinese m...Obesity,a widespread global health issue,is frequently linked to disrupted lipid metabolism,resulting in excessive accumulation of adipose tissue and associated health complications.Acupuncture,a traditional Chinese medical modality,has exhibited potential as a viable intervention for addressing obesity.The underlying mechanism proposed involves the stimulation of specific acupoints to exert a regulatory influence on hepatic function.The liver has a central role in lipid metabolism,including processes such as lipid synthesis,storage and distribution.Acupuncture is believed to enhance the liver’s efficiency in processing lipids,thereby reducing lipid accumulation and improving metabolic functions.Research indicates that acupuncture can influence the expression of certain genes and proteins involved in lipid metabolism in the liver.This includes upregulating genes that promote lipid breakdown and oxidation,and downregulating those involved in lipid synthesis.Additionally,acupuncture has been shown to improve insulin sensitivity,which is crucial for the regulation of lipid metabolism.Furthermore,the potential anti-inflammatory effects of acupuncture may play a significant role in its efficacy for the treatment of obesity.The presence of chronic inflammation has been strongly associated with metabolic disorders such as obesity.Through its ability to mitigate inflammation,acupuncture can potentially aid in the restoration of lipid metabolism and the reduction of body weight.Moreover,the amelioration of hepatic oxidative stress represents another mechanism by which acupuncture may contribute to the reduction of lipid deposition.Notably,the liver,being the primary site of lipid metabolism,maintains communication with various organs including the brain,adipose tissue,skeletal muscle and intestines.This perspective opens new avenues for the treatment of obesity,emphasizing the importance of holistic approaches in managing complex metabolic disorders.展开更多
Manganese-based oxide electrode materials suffer from severe Jahn-Teller(J-T)distortion,leading to severe cycle instability in sodium ion storage.However,it is difficult to adjust the electron at d orbitals exactly to...Manganese-based oxide electrode materials suffer from severe Jahn-Teller(J-T)distortion,leading to severe cycle instability in sodium ion storage.However,it is difficult to adjust the electron at d orbitals exactly to a low spin state to eliminate orbital degeneracy and suppress J-T distortion fundamentally.This article constructed concentration-controllable Mn/O coupled vacancy and amorphous network in Mn_(3)O_(4) and coated it with nitrogen-doped carbon aerogel(Mn_(3-x)O_(4-y)@NCA).The existence of Mn/O vacancies has been confirmed by scanning transmission electron microscopy(STEM)and positron annihilation lifetime spectroscopy(PALS).Atomic absorption spectroscopy(AAS)and X-ray photoelectron spectroscopy(XPS)determine the most optimal ratio of Mn/O vacancies for sodium ion storage is 1:2.Density functional theory(DFT)calculations prove that Mn/O coupled vacancies with the ratio of 1:2could exactly induce a low spin states and a d~4 electron configuration of Mn,suppressing the J-T distortion successfully.The abundant amorphous regions can shorten the transport distance of sodium ions,increase the electrochemically active sites and improve the pseudocapacitance response.From the synergetic effect of Mn/O coupled vacancies and amorphous regions,Mn_(3-x)O_(4-y)@NCA exhibits an energy density of 37.5 W h kg^(-1)and an ultra-high power density of 563 W kg^(-1)in an asymmetric supercapacitor.In sodium-ion batteries,it demonstrates high reversible capacity and exceptional cycling stability.This research presents a new method to improve the Na^(+)storage performance in manganese-based oxide,which is expected to be generalized to other structural distortion.展开更多
Segregation of solute atoms in the center of thick plates of the tempered steel can cause an inhomogeneous structural transformation and generate micron-sized inclusions,which leads to lamellar tearing of thick plate ...Segregation of solute atoms in the center of thick plates of the tempered steel can cause an inhomogeneous structural transformation and generate micron-sized inclusions,which leads to lamellar tearing of thick plate and decreases the plasticity and toughness.The formation and fragmentation mechanisms of micron-sized inclusions,like MnS and(Nb,Ti)C,in the center of thick plates were investigated by using thermodynamic calculations,finite element simulations,and electron backscatter diffraction characterization techniques.The results show that micron-sized inclusions nucleate and grow in the liquid phase,and under tensile loading,they exhibit three fragmentation mechanisms.The local stress during the fragmentation of inclusions is lower than the critical fracture stress of adjacent grains,and phase boundaries can effectively impede crack propagation into the matrix.The existence of a low proportion of high-angle grain boundaries(58.1%)and high Kernel average misorientation value(0.534°)in the segregation band promotes inclusions fragmentation and crack propagation.The difference in crack initiation and propagation direction caused by the morphology of inclusions and physical properties,as well as different matrix arrest abilities,is the main reasons for the diversity of inclusion fragmentation.展开更多
BACKGROUND Acute-on-chronic liver disease(AoCLD)accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases.AIM To explore the characterization of AoCLD to provide theoret...BACKGROUND Acute-on-chronic liver disease(AoCLD)accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases.AIM To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD.METHODS Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure(ACLF)study cohort were included in this study.The clinical characteristics and outcomes,and the 90-d survival rate associated with each clinical type of AoCLD were analyzed,using the Kaplan-Meier method and the log-rank test.RESULTS A total of 3375 patients with AoCLD were enrolled,including 1679(49.7%)patients with liver cirrhosis acute decompensation(LC-AD),850(25.2%)patients with ACLF,577(17.1%)patients with chronic hepatitis acute exacer-bation(CHAE),and 269(8.0%)patients with liver cirrhosis active phase(LC-A).The most common cause of chronic liver disease(CLD)was HBV infection(71.4%).The most common precipitants of AoCLD was bacterial infection(22.8%).The 90-d mortality rates of each clinical subtype of AoCLD were 43.4%(232/535)for type-C ACLF,36.0%(36/100)for type-B ACLF,27.0%(58/215)for type-A ACLF,9.0%(151/1679)for LC-AD,3.0%(8/269)for LC-A,and 1.2%(7/577)for CHAE.CONCLUSION HBV infection is the main cause of CLD,and bacterial infection is the main precipitant of AoCLD.The most common clinical type of AoCLD is LC-AD.Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.展开更多
Objective:To develop a deep learning model to predict lymph node(LN)status in clinical stage IA lung adeno-carcinoma patients.Methods:This diagnostic study included 1,009 patients with pathologically confirmed clinica...Objective:To develop a deep learning model to predict lymph node(LN)status in clinical stage IA lung adeno-carcinoma patients.Methods:This diagnostic study included 1,009 patients with pathologically confirmed clinical stage T1N0M0 lung adenocarcinoma from two independent datasets(699 from Cancer Hospital of Chinese Academy of Medical Sciences and 310 from PLA General Hospital)between January 2005 and December 2019.The Cancer Hospital dataset was randomly split into a training cohort(559 patients)and a validation cohort(140 patients)to train and tune a deep learning model based on a deep residual network(ResNet).The PLA Hospital dataset was used as a testing cohort to evaluate the generalization ability of the model.Thoracic radiologists manually segmented tumors and interpreted high-resolution computed tomography(HRCT)features for the model.The predictive performance was assessed by area under the curves(AUCs),accuracy,precision,recall,and F1 score.Subgroup analysis was performed to evaluate the potential bias of the study population.Results:A total of 1,009 patients were included in this study;409(40.5%)were male and 600(59.5%)were female.The median age was 57.0 years(inter-quartile range,IQR:50.0-64.0).The deep learning model achieved AUCs of 0.906(95%CI:0.873-0.938)and 0.893(95%CI:0.857-0.930)for predicting pN0 disease in the testing cohort and a non-pure ground glass nodule(non-pGGN)testing cohort,respectively.No significant difference was detected between the testing cohort and the non-pGGN testing cohort(P=0.622).The precisions of this model for predicting pN0 disease were 0.979(95%CI:0.963-0.995)and 0.983(95%CI:0.967-0.998)in the testing cohort and the non-pGGN testing cohort,respectively.The deep learning model achieved AUCs of 0.848(95%CI:0.798-0.898)and 0.831(95%CI:0.776-0.887)for predicting pN2 disease in the testing cohort and the non-pGGN testing cohort,respectively.No significant difference was detected between the testing cohort and the non-pGGN testing cohort(P=0.657).The recalls of this model for predicting pN2 disease were 0.903(95%CI:0.870-0.936)and 0.931(95%CI:0.901-0.961)in the testing cohort and the non-pGGN testing cohort,respectively.Conclusions:The superior performance of the deep learning model will help to target the extension of lymph node dissection and reduce the ineffective lymph node dissection in early-stage lung adenocarcinoma patients.展开更多
Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain met...Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.展开更多
Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular...Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.展开更多
Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cereb...Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.展开更多
Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these...Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.展开更多
Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage se...Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.展开更多
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 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 the National Natural Science Foundation of China(No.82274634).
文摘Obesity,a widespread global health issue,is frequently linked to disrupted lipid metabolism,resulting in excessive accumulation of adipose tissue and associated health complications.Acupuncture,a traditional Chinese medical modality,has exhibited potential as a viable intervention for addressing obesity.The underlying mechanism proposed involves the stimulation of specific acupoints to exert a regulatory influence on hepatic function.The liver has a central role in lipid metabolism,including processes such as lipid synthesis,storage and distribution.Acupuncture is believed to enhance the liver’s efficiency in processing lipids,thereby reducing lipid accumulation and improving metabolic functions.Research indicates that acupuncture can influence the expression of certain genes and proteins involved in lipid metabolism in the liver.This includes upregulating genes that promote lipid breakdown and oxidation,and downregulating those involved in lipid synthesis.Additionally,acupuncture has been shown to improve insulin sensitivity,which is crucial for the regulation of lipid metabolism.Furthermore,the potential anti-inflammatory effects of acupuncture may play a significant role in its efficacy for the treatment of obesity.The presence of chronic inflammation has been strongly associated with metabolic disorders such as obesity.Through its ability to mitigate inflammation,acupuncture can potentially aid in the restoration of lipid metabolism and the reduction of body weight.Moreover,the amelioration of hepatic oxidative stress represents another mechanism by which acupuncture may contribute to the reduction of lipid deposition.Notably,the liver,being the primary site of lipid metabolism,maintains communication with various organs including the brain,adipose tissue,skeletal muscle and intestines.This perspective opens new avenues for the treatment of obesity,emphasizing the importance of holistic approaches in managing complex metabolic disorders.
基金supported by the National Natural Science Foundation of China (22278231,22005165 and 22376110)the Natural Science Foundation Project of Shandong Province (ZR2022MB092 and ZR2023ME098)the Taishan Scholar Program (ts201712030)。
文摘Manganese-based oxide electrode materials suffer from severe Jahn-Teller(J-T)distortion,leading to severe cycle instability in sodium ion storage.However,it is difficult to adjust the electron at d orbitals exactly to a low spin state to eliminate orbital degeneracy and suppress J-T distortion fundamentally.This article constructed concentration-controllable Mn/O coupled vacancy and amorphous network in Mn_(3)O_(4) and coated it with nitrogen-doped carbon aerogel(Mn_(3-x)O_(4-y)@NCA).The existence of Mn/O vacancies has been confirmed by scanning transmission electron microscopy(STEM)and positron annihilation lifetime spectroscopy(PALS).Atomic absorption spectroscopy(AAS)and X-ray photoelectron spectroscopy(XPS)determine the most optimal ratio of Mn/O vacancies for sodium ion storage is 1:2.Density functional theory(DFT)calculations prove that Mn/O coupled vacancies with the ratio of 1:2could exactly induce a low spin states and a d~4 electron configuration of Mn,suppressing the J-T distortion successfully.The abundant amorphous regions can shorten the transport distance of sodium ions,increase the electrochemically active sites and improve the pseudocapacitance response.From the synergetic effect of Mn/O coupled vacancies and amorphous regions,Mn_(3-x)O_(4-y)@NCA exhibits an energy density of 37.5 W h kg^(-1)and an ultra-high power density of 563 W kg^(-1)in an asymmetric supercapacitor.In sodium-ion batteries,it demonstrates high reversible capacity and exceptional cycling stability.This research presents a new method to improve the Na^(+)storage performance in manganese-based oxide,which is expected to be generalized to other structural distortion.
基金the financial support to the National Natural Science Foundation of China(U20A20279)the technical support provided by Analysis and Test Center of Wuhan University of Science and Technology,China.
文摘Segregation of solute atoms in the center of thick plates of the tempered steel can cause an inhomogeneous structural transformation and generate micron-sized inclusions,which leads to lamellar tearing of thick plate and decreases the plasticity and toughness.The formation and fragmentation mechanisms of micron-sized inclusions,like MnS and(Nb,Ti)C,in the center of thick plates were investigated by using thermodynamic calculations,finite element simulations,and electron backscatter diffraction characterization techniques.The results show that micron-sized inclusions nucleate and grow in the liquid phase,and under tensile loading,they exhibit three fragmentation mechanisms.The local stress during the fragmentation of inclusions is lower than the critical fracture stress of adjacent grains,and phase boundaries can effectively impede crack propagation into the matrix.The existence of a low proportion of high-angle grain boundaries(58.1%)and high Kernel average misorientation value(0.534°)in the segregation band promotes inclusions fragmentation and crack propagation.The difference in crack initiation and propagation direction caused by the morphology of inclusions and physical properties,as well as different matrix arrest abilities,is the main reasons for the diversity of inclusion fragmentation.
基金Supported by The National Science and Technology Major Project,No.2018ZX10723203 and No.2018ZX10302206Hubei Province’s Outstanding Medical Academic Leader Program,Advantage Discipline Group(Public Health)Project in Higher Education of Hubei Province,No.2023PHXKQ1+2 种基金The Foundation of Health Commission of Hubei Province,No.WJ2021F037 and No.WJ2021M051Project of Hubei University of Medicine,No.FDFR201902 and No.YC2023047and The Hubei Provincial Technology Innovation Project,No.2023BCB129.
文摘BACKGROUND Acute-on-chronic liver disease(AoCLD)accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases.AIM To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD.METHODS Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure(ACLF)study cohort were included in this study.The clinical characteristics and outcomes,and the 90-d survival rate associated with each clinical type of AoCLD were analyzed,using the Kaplan-Meier method and the log-rank test.RESULTS A total of 3375 patients with AoCLD were enrolled,including 1679(49.7%)patients with liver cirrhosis acute decompensation(LC-AD),850(25.2%)patients with ACLF,577(17.1%)patients with chronic hepatitis acute exacer-bation(CHAE),and 269(8.0%)patients with liver cirrhosis active phase(LC-A).The most common cause of chronic liver disease(CLD)was HBV infection(71.4%).The most common precipitants of AoCLD was bacterial infection(22.8%).The 90-d mortality rates of each clinical subtype of AoCLD were 43.4%(232/535)for type-C ACLF,36.0%(36/100)for type-B ACLF,27.0%(58/215)for type-A ACLF,9.0%(151/1679)for LC-AD,3.0%(8/269)for LC-A,and 1.2%(7/577)for CHAE.CONCLUSION HBV infection is the main cause of CLD,and bacterial infection is the main precipitant of AoCLD.The most common clinical type of AoCLD is LC-AD.Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.
基金supported by the National Key R&D Program of China(grant numbers:2020AAA0109504,2023YFC2415200)CAMS Innovation Fund for Medical Sciences(grant number:2021-I2M-C&T-B-061)+5 种基金Beijing Hope Run Special Fund of Cancer Foundation of China(grant number:LC2022A22)the National Natural Science Foundation of China(grant numbers:81971619,81971580,92259302,82372053,91959205,82361168664,82022036,81971776)Beijing Natural Sci-ence Foundation(grant number:Z20J00105)Key-Area Research and Development Program of Guangdong Province(grant number:2021B0101420005)Strategic Priority Research Program of Chinese Academy of Sciences(grant number:XDB38040200)the Youth In-novation Promotion Association CAS(grant number:Y2021049).
文摘Objective:To develop a deep learning model to predict lymph node(LN)status in clinical stage IA lung adeno-carcinoma patients.Methods:This diagnostic study included 1,009 patients with pathologically confirmed clinical stage T1N0M0 lung adenocarcinoma from two independent datasets(699 from Cancer Hospital of Chinese Academy of Medical Sciences and 310 from PLA General Hospital)between January 2005 and December 2019.The Cancer Hospital dataset was randomly split into a training cohort(559 patients)and a validation cohort(140 patients)to train and tune a deep learning model based on a deep residual network(ResNet).The PLA Hospital dataset was used as a testing cohort to evaluate the generalization ability of the model.Thoracic radiologists manually segmented tumors and interpreted high-resolution computed tomography(HRCT)features for the model.The predictive performance was assessed by area under the curves(AUCs),accuracy,precision,recall,and F1 score.Subgroup analysis was performed to evaluate the potential bias of the study population.Results:A total of 1,009 patients were included in this study;409(40.5%)were male and 600(59.5%)were female.The median age was 57.0 years(inter-quartile range,IQR:50.0-64.0).The deep learning model achieved AUCs of 0.906(95%CI:0.873-0.938)and 0.893(95%CI:0.857-0.930)for predicting pN0 disease in the testing cohort and a non-pure ground glass nodule(non-pGGN)testing cohort,respectively.No significant difference was detected between the testing cohort and the non-pGGN testing cohort(P=0.622).The precisions of this model for predicting pN0 disease were 0.979(95%CI:0.963-0.995)and 0.983(95%CI:0.967-0.998)in the testing cohort and the non-pGGN testing cohort,respectively.The deep learning model achieved AUCs of 0.848(95%CI:0.798-0.898)and 0.831(95%CI:0.776-0.887)for predicting pN2 disease in the testing cohort and the non-pGGN testing cohort,respectively.No significant difference was detected between the testing cohort and the non-pGGN testing cohort(P=0.657).The recalls of this model for predicting pN2 disease were 0.903(95%CI:0.870-0.936)and 0.931(95%CI:0.901-0.961)in the testing cohort and the non-pGGN testing cohort,respectively.Conclusions:The superior performance of the deep learning model will help to target the extension of lymph node dissection and reduce the ineffective lymph node dissection in early-stage lung adenocarcinoma patients.
基金supported by the National Natural Science Foundation of China, No.82274616the Key Laboratory Project for General Universities in Guangdong Province, No.2019KSYS005Guangdong Province Science and Technology Plan International Cooperation Project, No.2020A0505100052 (all to QW)。
文摘Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.
基金supported by the National Natural Science Foundation of China,No.82101340(to FJ).
文摘Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.
基金supported by the National Natural Science Foundation of China,Nos.82260245(to YX),81660207(to YX),81960253(to YL),82160268(to YL),U1812403(to ZG)Science and Technology Projects of Guizhou Province,Nos.[2019]1440(to YX),[2020]1Z067(to WH)+1 种基金Cultivation Foundation of Guizhou Medical University,No.[20NSP069](to YX)Excellent Young Talents Plan of Guizhou Medical University,No.(2022)101(to WH)。
文摘Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.
基金supported by the Fundamental Research Funds for Central Public Welfare Research Institute,No.2020CZ-5(to WS and GS)the National Natural Science Foundation of China,No.31970970(to JSR)Fundamental Research Funds for the Central Universities,No.YWF-23-YG-QB-010(to JSR)。
文摘Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.
基金supported by the National Natural Science Foundation of China, No.61932008Natural Science Foundation of Shanghai, No.21ZR1403200 (both to JC)。
文摘Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.
