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
Gene mutations drive oncogene addiction in tumor cells,presenting opportunities for targeted gene therapy.Currently,targeted therapy is one of the most effective cancer treatment modalities.However,tumor cells demonst...Gene mutations drive oncogene addiction in tumor cells,presenting opportunities for targeted gene therapy.Currently,targeted therapy is one of the most effective cancer treatment modalities.However,tumor cells demonstrate remarkable plasticity,acquiring genetic mutations or activating alternative signaling pathways to evade targeted agents.Drug resistance frequently emerges,significantly diminishing the efficacy of targeted therapy.The precise causes of this resistance is unclear.The intricate interplay of immune and inflammatory pathways is integral to cancer development and response to treatment.Emerging evidence suggests that inflammatory pathways have pivotal roles in mediating resistance to targeted therapies across various cancer types,yet the exact mechanisms remain obscure.Herein we present an overview of the mechanisms underlying resistance to targeted therapies induced by inflammatory signaling,with a particular focus on inflammatory-driven resistance to EGFR-targeted therapies.展开更多
There are currently no targeted delivery systems to satisfactorily treat bone-related disorders.Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach...There are currently no targeted delivery systems to satisfactorily treat bone-related disorders.Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site.This coupled with repeatedly high dose usage that leads to severe side effects.展开更多
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
Osteoarthritis(OA)is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis.The cartilage matrix is mainly composed of collagen,a matrix protein with a hallmark trip...Osteoarthritis(OA)is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis.The cartilage matrix is mainly composed of collagen,a matrix protein with a hallmark triplehelix structure,which unfolds with collagen degradation on the cartilage surface.A collagen hybridizing peptide(CHP)is a synthetic peptide that binds the denatured collagen triple helix,conferring a potential diseasetargeting possibility for early-stage OA.Here,we constructed an albumin nanoparticle(An)conjugated with CHP,loaded with a chondrogenesis-promoting small molecule drug,kartogenin(KGN).The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA.Compared to treatment with KGN alone,CHP-KGN-An robustly attenuated cartilage degradation,synovitis,osteophyte formation,and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation.Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for earlystage OA therapeutics.展开更多
Object detection finds wide application in various sectors,including autonomous driving,industry,and healthcare.Recent studies have highlighted the vulnerability of object detection models built using deep neural netw...Object detection finds wide application in various sectors,including autonomous driving,industry,and healthcare.Recent studies have highlighted the vulnerability of object detection models built using deep neural networks when confronted with carefully crafted adversarial examples.This not only reveals their shortcomings in defending against malicious attacks but also raises widespread concerns about the security of existing systems.Most existing adversarial attack strategies focus primarily on image classification problems,failing to fully exploit the unique characteristics of object detectionmodels,thus resulting in widespread deficiencies in their transferability.Furthermore,previous research has predominantly concentrated on the transferability issues of non-targeted attacks,whereas enhancing the transferability of targeted adversarial examples presents even greater challenges.Traditional attack techniques typically employ cross-entropy as a loss measure,iteratively adjusting adversarial examples to match target categories.However,their inherent limitations restrict their broad applicability and transferability across different models.To address the aforementioned challenges,this study proposes a novel targeted adversarial attack method aimed at enhancing the transferability of adversarial samples across object detection models.Within the framework of iterative attacks,we devise a new objective function designed to mitigate consistency issues arising from cumulative noise and to enhance the separation between target and non-target categories(logit margin).Secondly,a data augmentation framework incorporating random erasing and color transformations is introduced into targeted adversarial attacks.This enhances the diversity of gradients,preventing overfitting to white-box models.Lastly,perturbations are applied only within the specified object’s bounding box to reduce the perturbation range,enhancing attack stealthiness.Experiments were conducted on the Microsoft Common Objects in Context(MS COCO)dataset using You Only Look Once version 3(YOLOv3),You Only Look Once version 8(YOLOv8),Faster Region-based Convolutional Neural Networks(Faster R-CNN),and RetinaNet.The results demonstrate a significant advantage of the proposed method in black-box settings.Among these,the success rate of RetinaNet transfer attacks reached a maximum of 82.59%.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
Myocardial infarction accompanied by diabetes mellitus is accepted as the most seri-ous type of coronary heart disease,and among the current treatment strategies,the precise delivery of protective drugs for inhibiting...Myocardial infarction accompanied by diabetes mellitus is accepted as the most seri-ous type of coronary heart disease,and among the current treatment strategies,the precise delivery of protective drugs for inhibiting cardiomyocyte apoptosis is still a challenge.In this study,we developed a biodegradable nanoparticles-based delivery system with excellent macrophage escape,cardiac targeting,and drug release prop-erties to achieve targeted therapy of myocardial infarction.Specifically,a copolymer of p(DMA–MPC–CD)combining self-adhesion,hydration lubrication,and targeting peptide binding site was successfully prepared by free radical copolymerization,and it was self-assembled on the surface of melatonin-loaded dendritic mesoporous silica nanoparticles(bMSNs)following the integration of adamantane-modified cardiac homing peptide(CHP)based on supramolecular host–guest interaction.Importantly,a hydration layer formed around the zwitterionic phosphorylcholine groups of the multifunctional nanoparticles,which was confirmed by the enhancement in hydra-tion lubrication and reduction in coefficient of friction,prevented the nanoparticles from phagocytosis by the macrophages.The in vivo bioluminescence imaging test indicated that the nanoparticles were endowed with satisfied cardiac targeting capa-bility,and the in vivo mice study demonstrated that the intravenous injection of drug-loaded nanoparticles(namely bMSNs–Mel@PDMC–CHP)effectively reduced cardiomyocyte apoptosis,alleviated myocardial interstitialfibrosis,and enhanced cardiac function.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
Poverty and income inequality are problems faced by many countries including China.Since the implementation of Targeted Poverty Alleviation(TPA),absolute poverty has been eradicated,meanwhile,Chinese rural residents...Poverty and income inequality are problems faced by many countries including China.Since the implementation of Targeted Poverty Alleviation(TPA),absolute poverty has been eradicated,meanwhile,Chinese rural residents'income and inequality have experienced unprecedented new dynamics,but still,very few studies have focused on them.Hence,we attempt to examine the new trends in Chinese farmers'income inequality and to understand its causes during this period.We observe that China's urban-rural income ratio has been shrinking and the urban-rural inequality has been decreasing from 2014 to 2021.The reduction in the Theil index indicates a decrease in the regional inequality of farmers'income as well,and the decline in inter-regional inequality among eight economic zones contributes about 80%to increased equality.These new trends are caused by the fact that,with the TPA,the incomes of rural residents especially that in destitute areas,grew faster than that of urban residents and farmers in prosperous areas.The higher share of non-agricultural industry and agricultural mechanization level have significant positive impact on regional equality of farmers'income,while urban-rural dual structure has significant negative inhibitory effects.The lowest farmers'income and the highest inequality in the Northwest,and the slowest growth in the Northeast deserve more attention in rural Revitalization.From these findings,we propose four policy implications that would be applied to improve Chinese farmers'income equality,govern relative poverty,and achieve common prosperity in the post-poverty era.展开更多
Objective This study aimed to explore the diagnostic value of novel technique-targeted next-generation sequencing(tNGS)of bronchoalveolar lavage fluid(BALF)in pulmonary mycobacterial infections.Methods This retrospect...Objective This study aimed to explore the diagnostic value of novel technique-targeted next-generation sequencing(tNGS)of bronchoalveolar lavage fluid(BALF)in pulmonary mycobacterial infections.Methods This retrospective study was conducted on patients who underwent bronchoscopy and tNGS,smear microscopy,and mycobacterial culture of BALF.Patients with positive Mycobacterium tuberculosis(MTB)culture or GeneXpert results were classified into the tuberculosis case group.Those diagnosed with nontuberculous mycobacteria(NTM)-pulmonary disease(NTM-PD)composed the case group of NTM-PD patients.The control group comprised patients without tuberculosis or NTM-PD.Sensitivity,specificity,and receiver operating characteristic(ROC)curves were used to evaluate the diagnostic performance.Results For tuberculosis patients with positive mycobacterial culture results,the areas under the ROC curves(AUCs)for tNGS,GeneXpert,and smear microscopy were 0.975(95%CI:0.935,1.000),0.925(95%CI:0.859,0.991),and 0.675(95%CI:0.563,0.787),respectively.For tuberculosis patients with positive GeneXpert results,the AUCs of tNGS,culture,and smear microscopy were 0.970(95%CI:0.931,1.000),0.850(95%CI:0.770,0.930),and 0.680(95%CI:0.579,0.781),respectively.For NTM-PD,the AUCs of tNGS,culture,and smear-positive but GeneXpert-negative results were 0.987(95%CI:0.967,1.000),0.750(95%CI:0.622,0.878),and 0.615(95%CI:0.479,0.752),respectively.The sensitivity and specificity of tNGS in NTM-PD patients were 100%and 97.5%,respectively.Conclusion tNGS demonstrated superior diagnostic efficacy in mycobacterial infection,indicating its potential for clinical application.展开更多
Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However...Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.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
Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attrac...Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.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
BACKGROUND Febrile convulsions are a common pediatric emergency that imposes significant psychological stress on children and their families.Targeted emergency care and psychological nursing are widely applied in clin...BACKGROUND Febrile convulsions are a common pediatric emergency that imposes significant psychological stress on children and their families.Targeted emergency care and psychological nursing are widely applied in clinical practice,but their value and impact on the management of pediatric febrile convulsions are unclear.AIM To determine the impact of targeted emergency nursing combined with psychological nursing on satisfaction in children with febrile convulsions.METHODS Data from 111 children with febrile convulsions who received treatment at Nantong Maternal and Child Health Care Hospital between June 2021 and October 2022 were analyzed.The control group consisted of 44 children who received conventional nursing care and the research group consisted of 67 children who received targeted emergency and psychological nursing.The time to fever resolution,time to resolution of convulsions,length of hospital stays,Pittsburgh Sleep Quality Index,patient compliance,nursing satisfaction of the parents,occurrence of complications during the nursing process,and parental anxiety and depression were compared between the control and research groups.Parental anxiety and depression were assessed using the Hamilton Rating Scale for Depression(HAMD)and the Hamilton Rating Scale for Anxiety(HAMA).RESULTS The fever resolution,convulsion disappearance,and hospitalization times were longer in the control group compared with the research group(P<0.0001).The time to falling asleep,sleep time,sleep quality,sleep disturbance,sleep efficiency,and daytime status scores were significantly better in the research group compared with the control group(P<0.0001).The HAMD and HAMA scores for parents of children in the research group were lower than the scores in the control group after nursing(P<0.05).Compliance with treatment of children in the research group was higher than in the control group(P<0.05).Parental satisfaction with nursing in the research group was higher than in the control group(P<0.05).The total complication rate of children in the control group was higher than in the research group(P<0.05).CONCLUSION Combining psychological nursing with targeted emergency nursing improved the satisfaction of children’s families and compliance with treatment and promoted early recovery of clinical symptoms and improvement of sleep quality.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
Cholangiocarcinoma(CCA),a highly aggressive bile duct cancer,is associated with late-stage diagnosis and limited treatment options,leading to poor patient outcomes.Early detection and personalized treatment strategies...Cholangiocarcinoma(CCA),a highly aggressive bile duct cancer,is associated with late-stage diagnosis and limited treatment options,leading to poor patient outcomes.Early detection and personalized treatment strategies are crucial.The study by Wang et al highlights the prognostic potential of the PEA3 subfamily genes(ETV1,ETV4,and ETV5)in CCA,identifying ETV4 as a particularly promising biomarker.Their bioinformatic analysis revealed that elevated ETV4 expression correlates with poorer survival,positioning it as a strong indicator of disease progression.These findings suggest that ETV4 could enhance prognostic precision and guide personalized therapies,although further validation through large-scale clinical trials is essential.Challenges in clinical application include the need for comprehensive experimental validation and addressing the tumor heterogeneity in CCA.Future research should focus on validating these biomarkers in diverse cohorts and developing targeted therapies,especially in regions where CCA is endemic.展开更多
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.
基金supported by the National Natural Science Foundation of China(Grant No.82372854)for Excellent Young Scholars,the Fundamental Research Funds for the Central Universities,and the National Science Foundation of Hubei Province(Grant No.2022CFA008).
文摘Gene mutations drive oncogene addiction in tumor cells,presenting opportunities for targeted gene therapy.Currently,targeted therapy is one of the most effective cancer treatment modalities.However,tumor cells demonstrate remarkable plasticity,acquiring genetic mutations or activating alternative signaling pathways to evade targeted agents.Drug resistance frequently emerges,significantly diminishing the efficacy of targeted therapy.The precise causes of this resistance is unclear.The intricate interplay of immune and inflammatory pathways is integral to cancer development and response to treatment.Emerging evidence suggests that inflammatory pathways have pivotal roles in mediating resistance to targeted therapies across various cancer types,yet the exact mechanisms remain obscure.Herein we present an overview of the mechanisms underlying resistance to targeted therapies induced by inflammatory signaling,with a particular focus on inflammatory-driven resistance to EGFR-targeted therapies.
基金financially supported by the National Natural Science Foundation of China (22305117)the Natural Science Foundation of Jiangsu Province (BK20220336)the Natural Science Foundation for Colleges and Universities in Jiangsu Province (22KJB180002)。
文摘There are currently no targeted delivery systems to satisfactorily treat bone-related disorders.Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site.This coupled with repeatedly high dose usage that leads to severe side effects.
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supported by the National Natural Science Foundation of China(82325035,82172481,32271409,82071977,and 92059104)the Six Talent Peaks Project of Jiangsu Province(WSW-079)+1 种基金the 2018 High-Level Health Team of Zhuhai,the Innovation Project of National Orthopedics and Sports Medicine Rehabilitation Clinical Medical Research Center(2021-NCRC-CXJJ-ZH-16)the Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine Foundation of Guangdong Province(2023LSYS001).Fig.1a was created by Biorender.com.
文摘Osteoarthritis(OA)is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis.The cartilage matrix is mainly composed of collagen,a matrix protein with a hallmark triplehelix structure,which unfolds with collagen degradation on the cartilage surface.A collagen hybridizing peptide(CHP)is a synthetic peptide that binds the denatured collagen triple helix,conferring a potential diseasetargeting possibility for early-stage OA.Here,we constructed an albumin nanoparticle(An)conjugated with CHP,loaded with a chondrogenesis-promoting small molecule drug,kartogenin(KGN).The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA.Compared to treatment with KGN alone,CHP-KGN-An robustly attenuated cartilage degradation,synovitis,osteophyte formation,and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation.Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for earlystage OA therapeutics.
文摘Object detection finds wide application in various sectors,including autonomous driving,industry,and healthcare.Recent studies have highlighted the vulnerability of object detection models built using deep neural networks when confronted with carefully crafted adversarial examples.This not only reveals their shortcomings in defending against malicious attacks but also raises widespread concerns about the security of existing systems.Most existing adversarial attack strategies focus primarily on image classification problems,failing to fully exploit the unique characteristics of object detectionmodels,thus resulting in widespread deficiencies in their transferability.Furthermore,previous research has predominantly concentrated on the transferability issues of non-targeted attacks,whereas enhancing the transferability of targeted adversarial examples presents even greater challenges.Traditional attack techniques typically employ cross-entropy as a loss measure,iteratively adjusting adversarial examples to match target categories.However,their inherent limitations restrict their broad applicability and transferability across different models.To address the aforementioned challenges,this study proposes a novel targeted adversarial attack method aimed at enhancing the transferability of adversarial samples across object detection models.Within the framework of iterative attacks,we devise a new objective function designed to mitigate consistency issues arising from cumulative noise and to enhance the separation between target and non-target categories(logit margin).Secondly,a data augmentation framework incorporating random erasing and color transformations is introduced into targeted adversarial attacks.This enhances the diversity of gradients,preventing overfitting to white-box models.Lastly,perturbations are applied only within the specified object’s bounding box to reduce the perturbation range,enhancing attack stealthiness.Experiments were conducted on the Microsoft Common Objects in Context(MS COCO)dataset using You Only Look Once version 3(YOLOv3),You Only Look Once version 8(YOLOv8),Faster Region-based Convolutional Neural Networks(Faster R-CNN),and RetinaNet.The results demonstrate a significant advantage of the proposed method in black-box settings.Among these,the success rate of RetinaNet transfer attacks reached a maximum of 82.59%.
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National Natural Science Foundation of China,Grant/Award Numbers:52275199,82073833,52335004,52022043Beijing-Tianjin-Hebei Fundamental Research Cooperation Project,Grant/Award Number:J230001+1 种基金Hainan Provincial Social Development Fund,Grant/Award Number:ZDYF2023SHFZ145National Key Research and Development Program of China,Grant/Award Numbers:2022YFC3600500,2022YFC3600502。
文摘Myocardial infarction accompanied by diabetes mellitus is accepted as the most seri-ous type of coronary heart disease,and among the current treatment strategies,the precise delivery of protective drugs for inhibiting cardiomyocyte apoptosis is still a challenge.In this study,we developed a biodegradable nanoparticles-based delivery system with excellent macrophage escape,cardiac targeting,and drug release prop-erties to achieve targeted therapy of myocardial infarction.Specifically,a copolymer of p(DMA–MPC–CD)combining self-adhesion,hydration lubrication,and targeting peptide binding site was successfully prepared by free radical copolymerization,and it was self-assembled on the surface of melatonin-loaded dendritic mesoporous silica nanoparticles(bMSNs)following the integration of adamantane-modified cardiac homing peptide(CHP)based on supramolecular host–guest interaction.Importantly,a hydration layer formed around the zwitterionic phosphorylcholine groups of the multifunctional nanoparticles,which was confirmed by the enhancement in hydra-tion lubrication and reduction in coefficient of friction,prevented the nanoparticles from phagocytosis by the macrophages.The in vivo bioluminescence imaging test indicated that the nanoparticles were endowed with satisfied cardiac targeting capa-bility,and the in vivo mice study demonstrated that the intravenous injection of drug-loaded nanoparticles(namely bMSNs–Mel@PDMC–CHP)effectively reduced cardiomyocyte apoptosis,alleviated myocardial interstitialfibrosis,and enhanced cardiac function.
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.
基金supported by the GanSu Provincial Science and Technology Program(No.22ZD6FA005)the Strategic Priority Research Program of Chinese Academy of Sciences(No.XDA23060704).
文摘Poverty and income inequality are problems faced by many countries including China.Since the implementation of Targeted Poverty Alleviation(TPA),absolute poverty has been eradicated,meanwhile,Chinese rural residents'income and inequality have experienced unprecedented new dynamics,but still,very few studies have focused on them.Hence,we attempt to examine the new trends in Chinese farmers'income inequality and to understand its causes during this period.We observe that China's urban-rural income ratio has been shrinking and the urban-rural inequality has been decreasing from 2014 to 2021.The reduction in the Theil index indicates a decrease in the regional inequality of farmers'income as well,and the decline in inter-regional inequality among eight economic zones contributes about 80%to increased equality.These new trends are caused by the fact that,with the TPA,the incomes of rural residents especially that in destitute areas,grew faster than that of urban residents and farmers in prosperous areas.The higher share of non-agricultural industry and agricultural mechanization level have significant positive impact on regional equality of farmers'income,while urban-rural dual structure has significant negative inhibitory effects.The lowest farmers'income and the highest inequality in the Northwest,and the slowest growth in the Northeast deserve more attention in rural Revitalization.From these findings,we propose four policy implications that would be applied to improve Chinese farmers'income equality,govern relative poverty,and achieve common prosperity in the post-poverty era.
文摘Objective This study aimed to explore the diagnostic value of novel technique-targeted next-generation sequencing(tNGS)of bronchoalveolar lavage fluid(BALF)in pulmonary mycobacterial infections.Methods This retrospective study was conducted on patients who underwent bronchoscopy and tNGS,smear microscopy,and mycobacterial culture of BALF.Patients with positive Mycobacterium tuberculosis(MTB)culture or GeneXpert results were classified into the tuberculosis case group.Those diagnosed with nontuberculous mycobacteria(NTM)-pulmonary disease(NTM-PD)composed the case group of NTM-PD patients.The control group comprised patients without tuberculosis or NTM-PD.Sensitivity,specificity,and receiver operating characteristic(ROC)curves were used to evaluate the diagnostic performance.Results For tuberculosis patients with positive mycobacterial culture results,the areas under the ROC curves(AUCs)for tNGS,GeneXpert,and smear microscopy were 0.975(95%CI:0.935,1.000),0.925(95%CI:0.859,0.991),and 0.675(95%CI:0.563,0.787),respectively.For tuberculosis patients with positive GeneXpert results,the AUCs of tNGS,culture,and smear microscopy were 0.970(95%CI:0.931,1.000),0.850(95%CI:0.770,0.930),and 0.680(95%CI:0.579,0.781),respectively.For NTM-PD,the AUCs of tNGS,culture,and smear-positive but GeneXpert-negative results were 0.987(95%CI:0.967,1.000),0.750(95%CI:0.622,0.878),and 0.615(95%CI:0.479,0.752),respectively.The sensitivity and specificity of tNGS in NTM-PD patients were 100%and 97.5%,respectively.Conclusion tNGS demonstrated superior diagnostic efficacy in mycobacterial infection,indicating its potential for clinical application.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82104827 and 82274336)the National High Level Hospital Clinical Research Funding,China(Grant No.:2022-PUMCH-A-265)the Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine(Grant No.:CACM-2022-QNRC2-B14).
文摘Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.
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.
基金the National Natural Science Foundation of China(Grant No.:51803120).
文摘Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.
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BACKGROUND Febrile convulsions are a common pediatric emergency that imposes significant psychological stress on children and their families.Targeted emergency care and psychological nursing are widely applied in clinical practice,but their value and impact on the management of pediatric febrile convulsions are unclear.AIM To determine the impact of targeted emergency nursing combined with psychological nursing on satisfaction in children with febrile convulsions.METHODS Data from 111 children with febrile convulsions who received treatment at Nantong Maternal and Child Health Care Hospital between June 2021 and October 2022 were analyzed.The control group consisted of 44 children who received conventional nursing care and the research group consisted of 67 children who received targeted emergency and psychological nursing.The time to fever resolution,time to resolution of convulsions,length of hospital stays,Pittsburgh Sleep Quality Index,patient compliance,nursing satisfaction of the parents,occurrence of complications during the nursing process,and parental anxiety and depression were compared between the control and research groups.Parental anxiety and depression were assessed using the Hamilton Rating Scale for Depression(HAMD)and the Hamilton Rating Scale for Anxiety(HAMA).RESULTS The fever resolution,convulsion disappearance,and hospitalization times were longer in the control group compared with the research group(P<0.0001).The time to falling asleep,sleep time,sleep quality,sleep disturbance,sleep efficiency,and daytime status scores were significantly better in the research group compared with the control group(P<0.0001).The HAMD and HAMA scores for parents of children in the research group were lower than the scores in the control group after nursing(P<0.05).Compliance with treatment of children in the research group was higher than in the control group(P<0.05).Parental satisfaction with nursing in the research group was higher than in the control group(P<0.05).The total complication rate of children in the control group was higher than in the research group(P<0.05).CONCLUSION Combining psychological nursing with targeted emergency nursing improved the satisfaction of children’s families and compliance with treatment and promoted early recovery of clinical symptoms and improvement of sleep quality.
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Cholangiocarcinoma(CCA),a highly aggressive bile duct cancer,is associated with late-stage diagnosis and limited treatment options,leading to poor patient outcomes.Early detection and personalized treatment strategies are crucial.The study by Wang et al highlights the prognostic potential of the PEA3 subfamily genes(ETV1,ETV4,and ETV5)in CCA,identifying ETV4 as a particularly promising biomarker.Their bioinformatic analysis revealed that elevated ETV4 expression correlates with poorer survival,positioning it as a strong indicator of disease progression.These findings suggest that ETV4 could enhance prognostic precision and guide personalized therapies,although further validation through large-scale clinical trials is essential.Challenges in clinical application include the need for comprehensive experimental validation and addressing the tumor heterogeneity in CCA.Future research should focus on validating these biomarkers in diverse cohorts and developing targeted therapies,especially in regions where CCA is endemic.