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 authors regret that there was an error in Fig.3 of the published article.The area under the curve(AUC)and 95%confidence interval(CI)values for the prediction of N2 disease were incorrectly displayed in the figure....The authors regret that there was an error in Fig.3 of the published article.The area under the curve(AUC)and 95%confidence interval(CI)values for the prediction of N2 disease were incorrectly displayed in the figure.This graphical error does not affect the study conclusions or the reported results elsewhere in the manuscript.The corrected version of Fig.3 is provided below.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
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
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
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
The influence of Hf on the precipitation behavior of γ'phase and the subsequent tensile properties of a Ni-Cr-Mo alloy after long-term thermal exposure was investigated.The results reveal that the addition of Hf ...The influence of Hf on the precipitation behavior of γ'phase and the subsequent tensile properties of a Ni-Cr-Mo alloy after long-term thermal exposure was investigated.The results reveal that the addition of Hf increases the average diameter ofγ'phases after thermal exposure at 700℃ for 5000 h,which enhances the critical resolved shear stress required for dislocations to shear the γ'phases in the Ni-Cr-Mo alloy.Simultaneously,element Hf incorporated into the γ'phases increases the lattice mismatch between the γ'and γ phase,thereby strengthening the coherency strengthening effect.These two factors collectively contribute to the enhanced strength of the alloy.Thus,Hf alloying effectively improves the yield strength of the Ni-Cr-Mo alloy after thermal exposure at 700℃.展开更多
The development of materials with excellent microwave absorption(MWA)and electromagnetic interference(EMI)shielding performances has currently received attention.Herein,mesophase pitch-based carbon foam(MPCF)with 3D i...The development of materials with excellent microwave absorption(MWA)and electromagnetic interference(EMI)shielding performances has currently received attention.Herein,mesophase pitch-based carbon foam(MPCF)with 3D interconnected pore structure was prepared through the high pressure pyrolysis of mesophase coal tar pitch.It is found that the 3D interconnected cellular pores of MPCF facilitate multiple reflections of electromagnetic waves,which results in the minimum reflection loss(RLmin)value of MPCF reaches-37.84 dB with the effective absorption bandwidth(EAB)of 5.44 GHz at a thickness of 2.70 mm,and the total average electromagnetic shielding effectiveness(SE_(T))under 3.00 mm thickness achieves 26.52 dB in X-band.Subsequently,MPCF is activated by KOH to obtain activated carbon foam(A-MPCF).The average SE_(T)of A-MPCF achieves 103.00 dB for abundant nanopores on the pore cell walls,which leads to a transition from the multiple reflections of electromagnetic waves on the walls to diffuse reflection.Unfortunately,the reflection coefficient(R)of A-MPCF increases from 0.78 to 0.90.To reduce the R value,Fe_(3)O_(4)/A-MPCF was fabricated via the in situ growth of nano Fe_(3)O_(4)on A-MPCF.Consequently,the R value of Fe_(3)O_(4)/A-MPCF was reduced from 0.90 to 0.74,whereas the MWA performance was only slightly decreased.This work proposes a simple strategy for simultaneously adjusting MWA and EMI shielding performances of materials.展开更多
Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mecha...Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.展开更多
Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance...Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.展开更多
This study investigates the relationship between atmospheric stratification (i.e., static stability given by N^(2)) and the vertical energy transfer of stationary planetary waves, and further illustrates the underlyin...This study investigates the relationship between atmospheric stratification (i.e., static stability given by N^(2)) and the vertical energy transfer of stationary planetary waves, and further illustrates the underlying physical mechanism. Specifically, for the simplified case of constant stratospheric N^(2), the refractive index square of planetary waves has a theoretical tendency to increase first and then decrease with an increased N^(2), whereas the group velocity weakens. Mechanistically, this behavior can be understood as an intensified suppression of vertical isentropic surface displacement caused by meridional heat transport of planetary waves under strong N^(2) conditions. Observational analysis corroborates this finding, demonstrating a reduction in the vertical-propagation velocity of waves with increased N^(2). A linear, quasi- geostrophic, mid-latitude beta-plane model with a constant background westerly wind and a prescribed N^(2) applicable to the stratosphere is used to obtain analytic solutions. In this model, the planetary waves are initiated by steady energy influx from the lower boundary. The analysis indicates that under strong N^(2) conditions, the amplitude of planetary waves can be sufficiently increased by the effective energy convergence due to the slowing vertical energy transfer, resulting in a streamfunction response in this model that contains more energy. For N^(2) with a quasi-linear vertical variation, the results bear a resemblance to the constant case, except that the wave amplitude and oscillating frequency show some vertical variations.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.
文摘The authors regret that there was an error in Fig.3 of the published article.The area under the curve(AUC)and 95%confidence interval(CI)values for the prediction of N2 disease were incorrectly displayed in the figure.This graphical error does not affect the study conclusions or the reported results elsewhere in the manuscript.The corrected version of Fig.3 is provided below.
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 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 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National Key Research and Development Program of China(2021YFB3704103)National Natural Science Foundation of China(51571191)。
文摘The influence of Hf on the precipitation behavior of γ'phase and the subsequent tensile properties of a Ni-Cr-Mo alloy after long-term thermal exposure was investigated.The results reveal that the addition of Hf increases the average diameter ofγ'phases after thermal exposure at 700℃ for 5000 h,which enhances the critical resolved shear stress required for dislocations to shear the γ'phases in the Ni-Cr-Mo alloy.Simultaneously,element Hf incorporated into the γ'phases increases the lattice mismatch between the γ'and γ phase,thereby strengthening the coherency strengthening effect.These two factors collectively contribute to the enhanced strength of the alloy.Thus,Hf alloying effectively improves the yield strength of the Ni-Cr-Mo alloy after thermal exposure at 700℃.
基金Supported by the National Natural Science Foundation of China(22378181).
文摘The development of materials with excellent microwave absorption(MWA)and electromagnetic interference(EMI)shielding performances has currently received attention.Herein,mesophase pitch-based carbon foam(MPCF)with 3D interconnected pore structure was prepared through the high pressure pyrolysis of mesophase coal tar pitch.It is found that the 3D interconnected cellular pores of MPCF facilitate multiple reflections of electromagnetic waves,which results in the minimum reflection loss(RLmin)value of MPCF reaches-37.84 dB with the effective absorption bandwidth(EAB)of 5.44 GHz at a thickness of 2.70 mm,and the total average electromagnetic shielding effectiveness(SE_(T))under 3.00 mm thickness achieves 26.52 dB in X-band.Subsequently,MPCF is activated by KOH to obtain activated carbon foam(A-MPCF).The average SE_(T)of A-MPCF achieves 103.00 dB for abundant nanopores on the pore cell walls,which leads to a transition from the multiple reflections of electromagnetic waves on the walls to diffuse reflection.Unfortunately,the reflection coefficient(R)of A-MPCF increases from 0.78 to 0.90.To reduce the R value,Fe_(3)O_(4)/A-MPCF was fabricated via the in situ growth of nano Fe_(3)O_(4)on A-MPCF.Consequently,the R value of Fe_(3)O_(4)/A-MPCF was reduced from 0.90 to 0.74,whereas the MWA performance was only slightly decreased.This work proposes a simple strategy for simultaneously adjusting MWA and EMI shielding performances of materials.
基金supported by the National Science Foundation of China,Nos.82325031(to FX),82030059(to YC),82102290(to YG),U23A20485(to YC)Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0505504(to FX),2023ZD0505500(to YC)the Key R&D Program of Shandong Province,No.2022ZLGX03(to YC).
文摘Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.
基金supported by Ministry of Science and Technology China Brain Initiative Grant,No.2022ZD0204702(to ZY)the National Natural Science Foundation of China,No.82371357(to LC)+2 种基金Foundation for Military Medicine,No.16QNP085(to ZY)Navy Medical University Basic Medical College“Yi Zhang”Basic Medical Talent Development and Support Program,Nos.JCYZRC-D-022(to TC)and JCYZRC-D-024(to HD)Science and Technology Innovation Special Fund of Shanghai Baoshan District,No.2023-E-05(to YW).
文摘Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.
基金supported by the National Natural Science Foundation of China(Grant No.42261134532,42405059,and U2342212)。
文摘This study investigates the relationship between atmospheric stratification (i.e., static stability given by N^(2)) and the vertical energy transfer of stationary planetary waves, and further illustrates the underlying physical mechanism. Specifically, for the simplified case of constant stratospheric N^(2), the refractive index square of planetary waves has a theoretical tendency to increase first and then decrease with an increased N^(2), whereas the group velocity weakens. Mechanistically, this behavior can be understood as an intensified suppression of vertical isentropic surface displacement caused by meridional heat transport of planetary waves under strong N^(2) conditions. Observational analysis corroborates this finding, demonstrating a reduction in the vertical-propagation velocity of waves with increased N^(2). A linear, quasi- geostrophic, mid-latitude beta-plane model with a constant background westerly wind and a prescribed N^(2) applicable to the stratosphere is used to obtain analytic solutions. In this model, the planetary waves are initiated by steady energy influx from the lower boundary. The analysis indicates that under strong N^(2) conditions, the amplitude of planetary waves can be sufficiently increased by the effective energy convergence due to the slowing vertical energy transfer, resulting in a streamfunction response in this model that contains more energy. For N^(2) with a quasi-linear vertical variation, the results bear a resemblance to the constant case, except that the wave amplitude and oscillating frequency show some vertical variations.
