Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescen...Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.展开更多
The recycling of spent batteries has become increasingly important owing to their wide applications,abundant raw material supply,and sustainable development.Compared with the degraded cathode,spent anode graphite ofte...The recycling of spent batteries has become increasingly important owing to their wide applications,abundant raw material supply,and sustainable development.Compared with the degraded cathode,spent anode graphite often has a relatively intact structure with few defects after long cycling.Yet,most spent graphite is simply burned or discarded due to its limited value and inferior performance on using conventional recycling methods that are complex,have low efficiency,and fail in performance restoration.Herein,we propose a fast,efficient,and“intelligent”strategy to regenerate and upcycle spent graphite based on defect‐driven targeted remediation.Using Sn as a nanoscale healant,we used rapid heating(~50 ms)to enable dynamic Sn droplets to automatically nucleate around the surface defects on the graphite upon cooling owing to strong binding to the defects(~5.84 eV/atom),thus simultaneously achieving Sn dispersion and graphite remediation.As a result,the regenerated graphite showed enhanced capacity and cycle stability(458.9 mAh g^(−1) at 0.2 A g^(−1) after 100 cycles),superior to those of commercial graphite.Benefiting from the self‐adaption of Sn dispersion,spent graphite with different degrees of defects can be regenerated to similar structures and performance.EverBatt analysis indicates that targeted regeneration and upcycling have significantly lower energy consumption(~99%reduction)and near‐zero CO_(2) emission,and yield much higher profit than hydrometallurgy,which opens a new avenue for direct upcycling of spend graphite in an efficient,green,and profitable manner for sustainable battery manufacture.展开更多
As an important mechanism in multi-agent interaction,communication can make agents form complex team relationships rather than constitute a simple set of multiple independent agents.However,the existing communication ...As an important mechanism in multi-agent interaction,communication can make agents form complex team relationships rather than constitute a simple set of multiple independent agents.However,the existing communication schemes can bring much timing redundancy and irrelevant messages,which seriously affects their practical application.To solve this problem,this paper proposes a targeted multiagent communication algorithm based on state control(SCTC).The SCTC uses a gating mechanism based on state control to reduce the timing redundancy of communication between agents and determines the interaction relationship between agents and the importance weight of a communication message through a series connection of hard-and self-attention mechanisms,realizing targeted communication message processing.In addition,by minimizing the difference between the fusion message generated from a real communication message of each agent and a fusion message generated from the buffered message,the correctness of the final action choice of the agent is ensured.Our evaluation using a challenging set of Star Craft II benchmarks indicates that the SCTC can significantly improve the learning performance and reduce the communication overhead between agents,thus ensuring better cooperation between agents.展开更多
BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more effi...BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.展开更多
Esophageal cancer (EC) is a prevalent malignant tumor that affects the digestive system and is often linked to a poor prognosis. The absence of effective early screening methods results in the diagnosis of esophageal ...Esophageal cancer (EC) is a prevalent malignant tumor that affects the digestive system and is often linked to a poor prognosis. The absence of effective early screening methods results in the diagnosis of esophageal cancer (EC) patients at advanced or metastatic stages. While historically considered incurable, ongoing advancements in medical research have led to the integration of various treatment modalities as primary approaches for managing advanced endometrial cancer. These modalities include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Notably, the introduction of targeted therapy and immunotherapy has significantly enhanced the survival rates of individuals with EC. Immunotherapy has appeared as the predominant treatment for advanced esophageal cancer, while targeted therapy faces certain obstacles. Consequently, this review primarily focuses on the advancements in targeted therapy for esophageal cancer (EC), evaluating the effectiveness and safety of relevant medications, and aiming to provide guidance for the comprehensive management of EC based on current research findings.展开更多
BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,...BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their importance in overcoming GSC-mediated resistance.Various therapeutic agents,notably RNA inhibitor/short hairpin RNA(27.3%),inhibitors(e.g.,LY294002,NVP-BEZ235)(24.2%),and monoclonal antibodies(e.g.,cetuximab)(9.1%),demonstrate versatility in targeted therapies.among 20 studies(60.6%),the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance(51.5%),followed by reductions in carmustine resistance(9.1%)and doxorubicin resistance(3.0%),while resistance to RTR is reduced in 42.4%of studies.CONCLUSION GSCs play a complex role in mediating radioresistance and chemoresistance,emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.展开更多
Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important ...Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric cancer.Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer.The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified.However,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer.Small-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future.Antibo-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab.Therefore,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.展开更多
Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone ...Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.展开更多
The Unintentional Insider Threat (UIT) concept highlights that insider threats might not always stem from malicious intent and can occur across various domains. This research examines how individuals with medical or p...The Unintentional Insider Threat (UIT) concept highlights that insider threats might not always stem from malicious intent and can occur across various domains. This research examines how individuals with medical or psychological issues might unintentionally become insider threats due to their perception of being targeted. Insights from the survey A Survey of Unintentional Medical Insider Threat Category indicate that such perceptions can be linked to underlying health conditions. The study Emotion Analysis Based on Belief of Targeted Individual Supporting Insider Threat Detection reveals that anger is a common emotion among these individuals. The findings suggest that UITs are often linked to medical or psychological issues, with anger being prevalent. To mitigate these risks, it is recommended that Insider Threat programs integrate expertise from medicine, psychology, and cybersecurity. Additionally, handwriting analysis is proposed as a potential tool for detecting insider threats, reflecting the evolving nature of threat assessment methodologies.展开更多
Introduction: Prostate cancer (PCa) is the third most prevalent cancer among Malaysian males, often diagnosed at advanced stages, leading to suboptimal outcomes. While transrectal ultrasound-guided systematic biopsy (...Introduction: Prostate cancer (PCa) is the third most prevalent cancer among Malaysian males, often diagnosed at advanced stages, leading to suboptimal outcomes. While transrectal ultrasound-guided systematic biopsy (TRUS-SB) is the primary diagnostic method, prebiopsy multiparametric magnetic resonance imaging (mpMRI) is gaining popularity in identifying suspicious lesions. This study addresses the lack of comprehensive investigations into the efficacy of cognitive registration TRUS targeted biopsy (COG-TB) compared to conventional TRUS-SB, considering the resource limitations of the Malaysian healthcare system. Materials and Methods: A retrospective cohort study was conducted in two Malaysian healthcare facilities. 116 adult patients with a prostate-specific antigen (PSA) level of more than 4 ng/mL who underwent both COG-TB and TRUS-SB between October 2020 and March 2022 were included. Primary outcomes were cancer detection rate and histopathological outcomes, including Gleason score. Results: COG-TB showed a higher overall cancer detection rate (50%) compared to TRUS-SB (44%). Clinically significant cancer detection rates were similar between COG-TB and TRUS-SB (37.1%). Further analysis revealed that both COG-TB and TRUS-SB detected clinically significant cancer in 30.2% of patients, did not detect it in 56.0%, and had conflicting findings in 16 patients (p Conclusion: COG-TB and TRUS-SB have comparable detection rates for clinically significant prostate cancer, with COG-TB showing a higher tendency to detect insignificant prostate cancer. Further studies comparing these methods are warranted.展开更多
Targeted radionuclide therapy,in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation,has addressed unmet clinical needs and improved outcomes for patients with cancer1-4.A ther...Targeted radionuclide therapy,in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation,has addressed unmet clinical needs and improved outcomes for patients with cancer1-4.A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue,which remains a major challenge5,6.A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution.Here we installed a sulfur(VI)fluoride exchange(SuFEx)chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance.When the engineered radiopharmaceutical binds to the tumour-specific protein,the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the'click'SuFEx reaction.展开更多
Prostate cancer is a common male malignant tumor,and bone metastasis is one of the common complications in the late stage of prostate cancer.The mechanism of prostate cancer bone metastasis is a complex process involv...Prostate cancer is a common male malignant tumor,and bone metastasis is one of the common complications in the late stage of prostate cancer.The mechanism of prostate cancer bone metastasis is a complex process involving multiple factors and steps.In recent years,with in-depth research on the mechanism of prostate cancer bone metastasis and the development of new drugs,important progress has been made in the treatment of prostate cancer bone metastasis.Based on this,this article introduces the mechanism of prostate cancer bone metastasis and the research progress of several bone-targeted drugs to provide reference and inspiration for future research.展开更多
Objective:To explore and analyze the effectiveness of targeted nursing in children with severe viral encephalitis complicated with respiratory failure.Methods:From April 2021 to April 2023,74 children with severe vira...Objective:To explore and analyze the effectiveness of targeted nursing in children with severe viral encephalitis complicated with respiratory failure.Methods:From April 2021 to April 2023,74 children with severe viral encephalitis complicated with respiratory failure admitted to the Department of Pediatrics of our hospital were selected as the research objects and divided into the target group(n=37)and the reference group(n=37).Targeted nursing was given to the target group,while general nursing was given to the reference group.Physical rehabilitation,motor scores,and lung function were compared between the groups.Results:The recovery time of limb abnormalities,convulsions,abnormal consciousness,and cranial nerve disorders in the target group was significantly better than that in the reference group(P<0.05).The motor function,joint activity and pain,sensory function,and total score of the target group were significantly lower than those of the reference group(P<0.05).After the intervention,lung function indicators including VC(vital capacity),FVC(forced vital capacity),and MVV(maximum voluntary ventilation)of the target group were better than those of the reference group(P<0.05).Conclusion:Targeted nursing can shorten the recovery period of severe viral encephalitis complicated with respiratory failure in children,speed up the recovery of motor function,and improve lung function.This nursing model has a significant application effect in children with severe viral encephalitis complicated with respiratory failure.展开更多
Nano-targeted delivery systems have been widely used for breast tumor drug delivery.Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor ...Nano-targeted delivery systems have been widely used for breast tumor drug delivery.Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor cells.However,targeted ligands have a significant impact on the safety and effectiveness of active delivery systems,limiting the clinical transformation of nanoparticles.Phytoestrogens have shown good biosafety characteristics and some affinity with the estrogen receptor.In the present study,molecular docking was used to select tanshinone IIA(Tan IIA)among phytoestrogens as a target ligand to be used in nanodelivery systems with somemodifications.Modified Tan IIA(Tan-NH2)showed a good biosafety profile and demonstrated tumor-targeting,anti-tumor and anti-tumor metastasis effects.Moreover,the ligand was utilized with the anti-tumor drug Dox-loaded mesoporous silica nanoparticles via chemical modification to generate a nanocomposite Tan-Dox-MSN.Tan-Dox-MSN had a uniform particle size,good dispersibility and high drug loading capacity.Validation experiments in vivo and in vitro showed that it also had a better targeting ability,anti-tumor effect and lower toxicity in normal organs.These results supported the idea that phytoestrogens with high affinity for the estrogen receptor could improve the therapeutic efficacy of nano-targeted delivery systems in breast tumors.展开更多
Colorectal cancer(CRC)is one of the most lethal and common malignancies in the world.Chemotherapy has been the conventional treatment for metastatic CRC(mCRC)patients.However,the effects of chemotherapy have been unsa...Colorectal cancer(CRC)is one of the most lethal and common malignancies in the world.Chemotherapy has been the conventional treatment for metastatic CRC(mCRC)patients.However,the effects of chemotherapy have been unsatisfactory.With the advent of targeted therapy,the survival of patients with CRC have been prolonged.Over the past 20 years,targeted therapy for CRC has achieved substantial progress.However,targeted therapy has the same challenge of drug resistance as chemotherapy.Consequently,exploring the resistance mechanism and finding strategies to address the resistance to targeted therapy,along with searching for novel effective regimens,is a constant challenge in the mCRC treatment,and it is also a hot research topic.In this review,we focus on the current status on resistance to existing targeted therapies in mCRC and discuss future developments.展开更多
The paper studies stochastic dynamics of a two-degree-of-freedom system,where a primary linear system is connected to a nonlinear energy sink with cubic stiffness nonlinearity and viscous damping.While the primary mas...The paper studies stochastic dynamics of a two-degree-of-freedom system,where a primary linear system is connected to a nonlinear energy sink with cubic stiffness nonlinearity and viscous damping.While the primary mass is subjected to a zero-mean Gaussian white noise excitation,the main objective of this study is to maximise the efficiency of the targeted energy transfer in the system.A surrogate optimisation algorithm is proposed for this purpose and adopted for the stochastic framework.The optimisations are conducted separately for the nonlinear stiffness coefficient alone as well as for both the nonlinear stiffness and damping coefficients together.Three different optimisation cost functions,based on either energy of the system’s components or the dissipated energy,are considered.The results demonstrate some clear trends in values of the nonlinear energy sink coefficients and show the effect of different cost functions on the optimal values of the nonlinear system’s coefficients.展开更多
One-time application of mixed fertilizer formed by the compounding of two controlled-release nitrogen fertilizers(CRUs)with targeted N supply during the periods from transplantation(TS)to panicle initiation(PI)and fro...One-time application of mixed fertilizer formed by the compounding of two controlled-release nitrogen fertilizers(CRUs)with targeted N supply during the periods from transplantation(TS)to panicle initiation(PI)and from PI to heading(HS)is expected to synchronize the double-peak N demand of rice.However,its effects on the yield and N use efficiency(NUE)of labor-intensive double-cropping rice were unknown.Two targeted CRU(CRU_(A)and CRU_(B))were compounded in five ratios(CRU_(A):CRU_(B)=10:0,7:3,5:5,3:7,and 0:10)to form five mixed fertilizers(BBFs):BBF1-5.A field experiment was performed to investigate the characteristics of N supply in early and late seasons under different BBFs and their effects on N uptake,yield,and ammonia volatilization(AV)loss from paddy fields of double-cropping rice.Conventional high-yield fertilization(CK,three split applications of urea)and zero-N treatments were established as controls.The N supply dropped significantly with the increased compound ratio of CRU_(B)during the period from TS to PI,but increased during the period from PI to HS.With the exception of the period from TS to PI in the late rice season,the N uptake of early and late rice maintained close synchronicity with the N supply of BBFs during the double-peak periods.Excessive N supply(BBF1 and BBF2)in the late rice season during the period from TS to PI increased N loss by AV.The effect of BBF on grain yield increase varied widely between seasons,irrespective of year.Among the BBFs,the BBF2 treatment of early rice not only stabilized the spikelets per panicle but also ensured a high number of effective panicles by promoting N uptake during the period from TS to PI and a high grain-filling percentage by appropriately reducing the N supply at the later PI stage,resulting in the highest rice yield.While stabilizing the effective panicle number,the BBF4 treatment of late rice increased the number of spikelets per panicle by promoting N uptake during the period from PI to HS,resulting in the highest rice yield.The two-year average yield and apparent N recovery efficiency of the BBF2 treatment during the early rice season were 9.6 t ha 1 and 45.3%,while those of late rice in BBF4 were 9.6 t ha 1 and 43.0%,respectively.The yield and NUE indexes of BBF2 in early rice and BBF4 in late rice showed no significant difference from those of CK.The AVs of BBF2 during the early rice season and of BBF4 during the late rice season were 50.0%and 76.8%lower,respectively,than those of CK.BBF2 and BBF4 could effectively replace conventional urea split fertilization in early and late rice seasons,ensuring rice yield and NUE and reducing AV loss in paddy fields.展开更多
Lithium-metal batteries are regarded as the"Holy Grail"of next-generation batteries.However,lithium dendrite and anode volume expansion in cycles seriously hinders lithium-metal battery applications.Herein,w...Lithium-metal batteries are regarded as the"Holy Grail"of next-generation batteries.However,lithium dendrite and anode volume expansion in cycles seriously hinders lithium-metal battery applications.Herein,we propose a precise and efficient strategy for stabilizing lithium-metal batteries via a lithiophilic Ag-modified Cu current host(Li@CuM/Ag).By applying the magnetron sputtering method,the lithiophilic silver layer can be anchored homogeneously on the Cu mesh.The lithiophilic silver layer effectively guides uniform Li deposition in the 3D host and realizes spatial control over Li nucleation.In addition,a dendrite-free lithium anode is successfully realized,which has been proven by in situ optical dynamic tests and Li deposition simulations.The symmetrical cell can maintain a low overpotential(230 mV)and long cycle life(90 h)at a large current of 10 mA cm^(-2)for a plating amount of 3 mAh cm^(-2).Furthermore,Li@CuM/Ag||LiCoO2 cells exhibited a high-capacity retention rate(86.39%)after 150 cycles at 2 C.Lithiophilic hosts based on magnetron sputtering provide a feasible strategy for applications of lithium-metal batteries.展开更多
Hepatocellular carcinoma(HCC)is a common malignant tumor that affecting many people's lives globally.The common risk factors for HCC include being overweight and obese.The liver is the center of lipid metabolism,s...Hepatocellular carcinoma(HCC)is a common malignant tumor that affecting many people's lives globally.The common risk factors for HCC include being overweight and obese.The liver is the center of lipid metabolism,synthesizing most cholesterol and fatty acids.Abnormal lipid metabolism is a significant feature of metabolic reprogramming in HCC and affects the prognosis of HCC patients by regulating inflammatory responses and changing the immune microenvironment.Targeted therapy and immunotherapy are being explored as the primary treatment strategies for HCC patients with unresectable tumors.Here,we detail the specific changes of lipid metabolism in HCC and its impact on both these therapies for HCC.HCC treatment strategies aimed at targeting lipid metabolism and how to integrate them with targeted therapy or immunotherapy rationally are also presented.展开更多
The weakly ionized plasma flows in aerospace are commonly simulated by the single-fluid model,which cannot describe certain nonequilibrium phenomena by finite collisions of particles,decreasing the fidelity of the sol...The weakly ionized plasma flows in aerospace are commonly simulated by the single-fluid model,which cannot describe certain nonequilibrium phenomena by finite collisions of particles,decreasing the fidelity of the solution.Based on an alternative formulation of the targeted essentially non-oscillatory(TENO)scheme,a novel high-order numerical scheme is proposed to simulate the two-fluid plasmas problems.The numerical flux is constructed by the TENO interpolation of the solution and its derivatives,instead of being reconstructed from the physical flux.The present scheme is used to solve the two sets of Euler equations coupled with Maxwell's equations.The numerical methods are verified by several classical plasma problems.The results show that compared with the original TENO scheme,the present scheme can suppress the non-physical oscillations and reduce the numerical dissipation.展开更多
基金supported by Dalian Youth Science and Technology Star Project(2020RQ121)the National Science Fund for Distinguished Young Scholars of China(31925031)+1 种基金Doctoral Scientific Research Foundation of Liaoning Province(2020-BS-211)Liaoning Province Education Administration(J2020101)。
文摘Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.
基金The Fundamental Research Funds for the Central Universities,HUST,Grant/Award Number:2021GCRC046The Open Fund of State Key Laboratory of New Textile Materials and Advanced Processing Technologies,Grant/Award Number:FZ2022005Natural Science Foundation of Hubei Province,China,Grant/Award Number:2022CFA031。
文摘The recycling of spent batteries has become increasingly important owing to their wide applications,abundant raw material supply,and sustainable development.Compared with the degraded cathode,spent anode graphite often has a relatively intact structure with few defects after long cycling.Yet,most spent graphite is simply burned or discarded due to its limited value and inferior performance on using conventional recycling methods that are complex,have low efficiency,and fail in performance restoration.Herein,we propose a fast,efficient,and“intelligent”strategy to regenerate and upcycle spent graphite based on defect‐driven targeted remediation.Using Sn as a nanoscale healant,we used rapid heating(~50 ms)to enable dynamic Sn droplets to automatically nucleate around the surface defects on the graphite upon cooling owing to strong binding to the defects(~5.84 eV/atom),thus simultaneously achieving Sn dispersion and graphite remediation.As a result,the regenerated graphite showed enhanced capacity and cycle stability(458.9 mAh g^(−1) at 0.2 A g^(−1) after 100 cycles),superior to those of commercial graphite.Benefiting from the self‐adaption of Sn dispersion,spent graphite with different degrees of defects can be regenerated to similar structures and performance.EverBatt analysis indicates that targeted regeneration and upcycling have significantly lower energy consumption(~99%reduction)and near‐zero CO_(2) emission,and yield much higher profit than hydrometallurgy,which opens a new avenue for direct upcycling of spend graphite in an efficient,green,and profitable manner for sustainable battery manufacture.
文摘As an important mechanism in multi-agent interaction,communication can make agents form complex team relationships rather than constitute a simple set of multiple independent agents.However,the existing communication schemes can bring much timing redundancy and irrelevant messages,which seriously affects their practical application.To solve this problem,this paper proposes a targeted multiagent communication algorithm based on state control(SCTC).The SCTC uses a gating mechanism based on state control to reduce the timing redundancy of communication between agents and determines the interaction relationship between agents and the importance weight of a communication message through a series connection of hard-and self-attention mechanisms,realizing targeted communication message processing.In addition,by minimizing the difference between the fusion message generated from a real communication message of each agent and a fusion message generated from the buffered message,the correctness of the final action choice of the agent is ensured.Our evaluation using a challenging set of Star Craft II benchmarks indicates that the SCTC can significantly improve the learning performance and reduce the communication overhead between agents,thus ensuring better cooperation between agents.
基金This study was reviewed and approved by the Ethics Committee of Zhongshan People’s Hospital(Approval No.2022-029).
文摘BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.
文摘Esophageal cancer (EC) is a prevalent malignant tumor that affects the digestive system and is often linked to a poor prognosis. The absence of effective early screening methods results in the diagnosis of esophageal cancer (EC) patients at advanced or metastatic stages. While historically considered incurable, ongoing advancements in medical research have led to the integration of various treatment modalities as primary approaches for managing advanced endometrial cancer. These modalities include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Notably, the introduction of targeted therapy and immunotherapy has significantly enhanced the survival rates of individuals with EC. Immunotherapy has appeared as the predominant treatment for advanced esophageal cancer, while targeted therapy faces certain obstacles. Consequently, this review primarily focuses on the advancements in targeted therapy for esophageal cancer (EC), evaluating the effectiveness and safety of relevant medications, and aiming to provide guidance for the comprehensive management of EC based on current research findings.
文摘BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their importance in overcoming GSC-mediated resistance.Various therapeutic agents,notably RNA inhibitor/short hairpin RNA(27.3%),inhibitors(e.g.,LY294002,NVP-BEZ235)(24.2%),and monoclonal antibodies(e.g.,cetuximab)(9.1%),demonstrate versatility in targeted therapies.among 20 studies(60.6%),the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance(51.5%),followed by reductions in carmustine resistance(9.1%)and doxorubicin resistance(3.0%),while resistance to RTR is reduced in 42.4%of studies.CONCLUSION GSCs play a complex role in mediating radioresistance and chemoresistance,emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.
文摘Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric cancer.Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer.The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified.However,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer.Small-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future.Antibo-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab.Therefore,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.
基金supported by the National Natural Science Foundation of China(#81872220 and#81703437)Xinjiang Uygur Autonomous Region Science and Technology Support Project(#2020E0290)+4 种基金Basic Public Welfare Research Project of Zhejiang Province(#LGF18H160034,LGC21B050011 and#LGF20H300012),Science and Technology Bureau of Jiaxing(2020AY10021)Key Research and Development and Transformation project of Qinghai Province(2021-SF-C20)Dutch Cancer Foundation(KWF project#10666)a Zhejiang Provincial Foreign Expert Program Grant,Zhejiang Provincial Key Natural Science Foundation of China(#Z20H160031)and Jiaxing Key Laboratory of Oncological Photodynamic Therapy and Targeted Drug Research,and“Innovative Jiaxing·Excellent Talent Support Program”-Top Talents in Technological Innovation.
文摘Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.
文摘The Unintentional Insider Threat (UIT) concept highlights that insider threats might not always stem from malicious intent and can occur across various domains. This research examines how individuals with medical or psychological issues might unintentionally become insider threats due to their perception of being targeted. Insights from the survey A Survey of Unintentional Medical Insider Threat Category indicate that such perceptions can be linked to underlying health conditions. The study Emotion Analysis Based on Belief of Targeted Individual Supporting Insider Threat Detection reveals that anger is a common emotion among these individuals. The findings suggest that UITs are often linked to medical or psychological issues, with anger being prevalent. To mitigate these risks, it is recommended that Insider Threat programs integrate expertise from medicine, psychology, and cybersecurity. Additionally, handwriting analysis is proposed as a potential tool for detecting insider threats, reflecting the evolving nature of threat assessment methodologies.
文摘Introduction: Prostate cancer (PCa) is the third most prevalent cancer among Malaysian males, often diagnosed at advanced stages, leading to suboptimal outcomes. While transrectal ultrasound-guided systematic biopsy (TRUS-SB) is the primary diagnostic method, prebiopsy multiparametric magnetic resonance imaging (mpMRI) is gaining popularity in identifying suspicious lesions. This study addresses the lack of comprehensive investigations into the efficacy of cognitive registration TRUS targeted biopsy (COG-TB) compared to conventional TRUS-SB, considering the resource limitations of the Malaysian healthcare system. Materials and Methods: A retrospective cohort study was conducted in two Malaysian healthcare facilities. 116 adult patients with a prostate-specific antigen (PSA) level of more than 4 ng/mL who underwent both COG-TB and TRUS-SB between October 2020 and March 2022 were included. Primary outcomes were cancer detection rate and histopathological outcomes, including Gleason score. Results: COG-TB showed a higher overall cancer detection rate (50%) compared to TRUS-SB (44%). Clinically significant cancer detection rates were similar between COG-TB and TRUS-SB (37.1%). Further analysis revealed that both COG-TB and TRUS-SB detected clinically significant cancer in 30.2% of patients, did not detect it in 56.0%, and had conflicting findings in 16 patients (p Conclusion: COG-TB and TRUS-SB have comparable detection rates for clinically significant prostate cancer, with COG-TB showing a higher tendency to detect insignificant prostate cancer. Further studies comparing these methods are warranted.
文摘Targeted radionuclide therapy,in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation,has addressed unmet clinical needs and improved outcomes for patients with cancer1-4.A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue,which remains a major challenge5,6.A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution.Here we installed a sulfur(VI)fluoride exchange(SuFEx)chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance.When the engineered radiopharmaceutical binds to the tumour-specific protein,the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the'click'SuFEx reaction.
基金Traditional Chinese Medicine and Integrated Traditional Chinese and Western Medicine Research Project of Tianjin Municipal Administration of Traditional Chinese Medicine(2021106)Beijing-Tianjin-Hebei Traditional Chinese Medicine Collaborative Development Specialty Alliance Construction Project(First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Qingxian County Traditional Chinese Medicine Hospital).
文摘Prostate cancer is a common male malignant tumor,and bone metastasis is one of the common complications in the late stage of prostate cancer.The mechanism of prostate cancer bone metastasis is a complex process involving multiple factors and steps.In recent years,with in-depth research on the mechanism of prostate cancer bone metastasis and the development of new drugs,important progress has been made in the treatment of prostate cancer bone metastasis.Based on this,this article introduces the mechanism of prostate cancer bone metastasis and the research progress of several bone-targeted drugs to provide reference and inspiration for future research.
文摘Objective:To explore and analyze the effectiveness of targeted nursing in children with severe viral encephalitis complicated with respiratory failure.Methods:From April 2021 to April 2023,74 children with severe viral encephalitis complicated with respiratory failure admitted to the Department of Pediatrics of our hospital were selected as the research objects and divided into the target group(n=37)and the reference group(n=37).Targeted nursing was given to the target group,while general nursing was given to the reference group.Physical rehabilitation,motor scores,and lung function were compared between the groups.Results:The recovery time of limb abnormalities,convulsions,abnormal consciousness,and cranial nerve disorders in the target group was significantly better than that in the reference group(P<0.05).The motor function,joint activity and pain,sensory function,and total score of the target group were significantly lower than those of the reference group(P<0.05).After the intervention,lung function indicators including VC(vital capacity),FVC(forced vital capacity),and MVV(maximum voluntary ventilation)of the target group were better than those of the reference group(P<0.05).Conclusion:Targeted nursing can shorten the recovery period of severe viral encephalitis complicated with respiratory failure in children,speed up the recovery of motor function,and improve lung function.This nursing model has a significant application effect in children with severe viral encephalitis complicated with respiratory failure.
基金supported by the Tianjin University of Traditional Chinese Medicine Scientific Research Project for the NewTeacher[grant number:XJS2022212]The Science and Technology Program of Tianjin[grant number:21YJDJC00020]The Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine[grant number:22HHZYSS00005].
文摘Nano-targeted delivery systems have been widely used for breast tumor drug delivery.Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor cells.However,targeted ligands have a significant impact on the safety and effectiveness of active delivery systems,limiting the clinical transformation of nanoparticles.Phytoestrogens have shown good biosafety characteristics and some affinity with the estrogen receptor.In the present study,molecular docking was used to select tanshinone IIA(Tan IIA)among phytoestrogens as a target ligand to be used in nanodelivery systems with somemodifications.Modified Tan IIA(Tan-NH2)showed a good biosafety profile and demonstrated tumor-targeting,anti-tumor and anti-tumor metastasis effects.Moreover,the ligand was utilized with the anti-tumor drug Dox-loaded mesoporous silica nanoparticles via chemical modification to generate a nanocomposite Tan-Dox-MSN.Tan-Dox-MSN had a uniform particle size,good dispersibility and high drug loading capacity.Validation experiments in vivo and in vitro showed that it also had a better targeting ability,anti-tumor effect and lower toxicity in normal organs.These results supported the idea that phytoestrogens with high affinity for the estrogen receptor could improve the therapeutic efficacy of nano-targeted delivery systems in breast tumors.
基金the National Natural Science Foundation of China,No.82073338Sichuan Science and Technology Support Project,No.2021YFSY0039 and No.22ZDYF0499+1 种基金1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project,West China Hospital,Sichuan University,No.2020HXFH0021.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,No.ZYJC21059.
文摘Colorectal cancer(CRC)is one of the most lethal and common malignancies in the world.Chemotherapy has been the conventional treatment for metastatic CRC(mCRC)patients.However,the effects of chemotherapy have been unsatisfactory.With the advent of targeted therapy,the survival of patients with CRC have been prolonged.Over the past 20 years,targeted therapy for CRC has achieved substantial progress.However,targeted therapy has the same challenge of drug resistance as chemotherapy.Consequently,exploring the resistance mechanism and finding strategies to address the resistance to targeted therapy,along with searching for novel effective regimens,is a constant challenge in the mCRC treatment,and it is also a hot research topic.In this review,we focus on the current status on resistance to existing targeted therapies in mCRC and discuss future developments.
基金funding for this work from NSF-CMMI 2009270 and EPSRC EP/V034391/1.
文摘The paper studies stochastic dynamics of a two-degree-of-freedom system,where a primary linear system is connected to a nonlinear energy sink with cubic stiffness nonlinearity and viscous damping.While the primary mass is subjected to a zero-mean Gaussian white noise excitation,the main objective of this study is to maximise the efficiency of the targeted energy transfer in the system.A surrogate optimisation algorithm is proposed for this purpose and adopted for the stochastic framework.The optimisations are conducted separately for the nonlinear stiffness coefficient alone as well as for both the nonlinear stiffness and damping coefficients together.Three different optimisation cost functions,based on either energy of the system’s components or the dissipated energy,are considered.The results demonstrate some clear trends in values of the nonlinear energy sink coefficients and show the effect of different cost functions on the optimal values of the nonlinear system’s coefficients.
基金provided by the National Key Research and Development Program of China(2018YFD0300904)Anhui Natural Science Foundation(2008085QC119)Key Fund Project of Anhui Department of Education(KJ2019A0176).
文摘One-time application of mixed fertilizer formed by the compounding of two controlled-release nitrogen fertilizers(CRUs)with targeted N supply during the periods from transplantation(TS)to panicle initiation(PI)and from PI to heading(HS)is expected to synchronize the double-peak N demand of rice.However,its effects on the yield and N use efficiency(NUE)of labor-intensive double-cropping rice were unknown.Two targeted CRU(CRU_(A)and CRU_(B))were compounded in five ratios(CRU_(A):CRU_(B)=10:0,7:3,5:5,3:7,and 0:10)to form five mixed fertilizers(BBFs):BBF1-5.A field experiment was performed to investigate the characteristics of N supply in early and late seasons under different BBFs and their effects on N uptake,yield,and ammonia volatilization(AV)loss from paddy fields of double-cropping rice.Conventional high-yield fertilization(CK,three split applications of urea)and zero-N treatments were established as controls.The N supply dropped significantly with the increased compound ratio of CRU_(B)during the period from TS to PI,but increased during the period from PI to HS.With the exception of the period from TS to PI in the late rice season,the N uptake of early and late rice maintained close synchronicity with the N supply of BBFs during the double-peak periods.Excessive N supply(BBF1 and BBF2)in the late rice season during the period from TS to PI increased N loss by AV.The effect of BBF on grain yield increase varied widely between seasons,irrespective of year.Among the BBFs,the BBF2 treatment of early rice not only stabilized the spikelets per panicle but also ensured a high number of effective panicles by promoting N uptake during the period from TS to PI and a high grain-filling percentage by appropriately reducing the N supply at the later PI stage,resulting in the highest rice yield.While stabilizing the effective panicle number,the BBF4 treatment of late rice increased the number of spikelets per panicle by promoting N uptake during the period from PI to HS,resulting in the highest rice yield.The two-year average yield and apparent N recovery efficiency of the BBF2 treatment during the early rice season were 9.6 t ha 1 and 45.3%,while those of late rice in BBF4 were 9.6 t ha 1 and 43.0%,respectively.The yield and NUE indexes of BBF2 in early rice and BBF4 in late rice showed no significant difference from those of CK.The AVs of BBF2 during the early rice season and of BBF4 during the late rice season were 50.0%and 76.8%lower,respectively,than those of CK.BBF2 and BBF4 could effectively replace conventional urea split fertilization in early and late rice seasons,ensuring rice yield and NUE and reducing AV loss in paddy fields.
基金supported by the National Natural Science Foundation of China(U1802256,21875107)the Basic Research Program of Frontier Leading Technologies in Jiangsu Province(BK20202008)+1 种基金the Free Exploration Basic Research Project in Shenzhen Virtual University Park(2021Szvup062)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Lithium-metal batteries are regarded as the"Holy Grail"of next-generation batteries.However,lithium dendrite and anode volume expansion in cycles seriously hinders lithium-metal battery applications.Herein,we propose a precise and efficient strategy for stabilizing lithium-metal batteries via a lithiophilic Ag-modified Cu current host(Li@CuM/Ag).By applying the magnetron sputtering method,the lithiophilic silver layer can be anchored homogeneously on the Cu mesh.The lithiophilic silver layer effectively guides uniform Li deposition in the 3D host and realizes spatial control over Li nucleation.In addition,a dendrite-free lithium anode is successfully realized,which has been proven by in situ optical dynamic tests and Li deposition simulations.The symmetrical cell can maintain a low overpotential(230 mV)and long cycle life(90 h)at a large current of 10 mA cm^(-2)for a plating amount of 3 mAh cm^(-2).Furthermore,Li@CuM/Ag||LiCoO2 cells exhibited a high-capacity retention rate(86.39%)after 150 cycles at 2 C.Lithiophilic hosts based on magnetron sputtering provide a feasible strategy for applications of lithium-metal batteries.
基金Supported by National Natural Science Foundation of China,No.81970453,and No.82270634Shanghai Science and Technology Innovation Action Plan Project,No.20XD1405100.
文摘Hepatocellular carcinoma(HCC)is a common malignant tumor that affecting many people's lives globally.The common risk factors for HCC include being overweight and obese.The liver is the center of lipid metabolism,synthesizing most cholesterol and fatty acids.Abnormal lipid metabolism is a significant feature of metabolic reprogramming in HCC and affects the prognosis of HCC patients by regulating inflammatory responses and changing the immune microenvironment.Targeted therapy and immunotherapy are being explored as the primary treatment strategies for HCC patients with unresectable tumors.Here,we detail the specific changes of lipid metabolism in HCC and its impact on both these therapies for HCC.HCC treatment strategies aimed at targeting lipid metabolism and how to integrate them with targeted therapy or immunotherapy rationally are also presented.
基金Project supported by the National Natural Science Foundation of China(Nos.12072246,11972272,11872286)the National Numerical Wind Tunnel Project of China(No.NNW2020ZT3-A23)。
文摘The weakly ionized plasma flows in aerospace are commonly simulated by the single-fluid model,which cannot describe certain nonequilibrium phenomena by finite collisions of particles,decreasing the fidelity of the solution.Based on an alternative formulation of the targeted essentially non-oscillatory(TENO)scheme,a novel high-order numerical scheme is proposed to simulate the two-fluid plasmas problems.The numerical flux is constructed by the TENO interpolation of the solution and its derivatives,instead of being reconstructed from the physical flux.The present scheme is used to solve the two sets of Euler equations coupled with Maxwell's equations.The numerical methods are verified by several classical plasma problems.The results show that compared with the original TENO scheme,the present scheme can suppress the non-physical oscillations and reduce the numerical dissipation.