The ratio of the number of emitted pions from the target side to that from the projectile side at target rapidity within the reaction plane is investigated for the study of the pion dynamics with an isospin-dependent ...The ratio of the number of emitted pions from the target side to that from the projectile side at target rapidity within the reaction plane is investigated for the study of the pion dynamics with an isospin-dependent quantum molecular dynamic model. The results show that high-energy pions are emitted preferentially towards the target side and, therefore, they are freezed out at the early stage of the collision. By contrast, low-energy pions are emitted predominantly in the opposite direction, which means that they are emitted in a later stage. This argument is based on the shadowing effect caused by the interaction of pions with the spectator matter in peripheral collisions at target or projectile rapidities. This phenomenon disappears in the central collision or at midrapidity due to the weaker shadowing effect. The calculated ratios are also compared with the experimental data.展开更多
The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains c...Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.展开更多
Using the back skin of the mice as the test object,UPLC was used to determine the retention rate of Glabridin(GLA)in the skin and subcutaneous fat pf mice with different dosage forms and different administration times...Using the back skin of the mice as the test object,UPLC was used to determine the retention rate of Glabridin(GLA)in the skin and subcutaneous fat pf mice with different dosage forms and different administration times,and to investigate the transdermal absorption effect of liquid crystal cream.The experimental results showed that the 0.5,1,2,4,6 and 8h skin retention rates of GLA in the liquid crystal cream group were 1.67,0.79,1.73,1.47,1.17 and 1.15 times higher than those of the ordinary cream group under the same dosage of administration,respectively.The 0.5,1,2,4,6 and 8 h fat retention rates of GLA in the normal cream group were 0.86,1.87,1.37,1.20,1.35 and 1.19 times higher than those in the liquid crystal group,respectively.Liquid crystal cream can significantly improve the skin retention of GLA,with certain slow and controlled release,and possesses certain skin targeting properties.展开更多
AIM:To explore whether plasma proteins serve as potential therapeutic targets for primary open angle glaucoma(POAG)based on a Mendelian randomization(MR)study.METHODS:Large-scale protein quantitative trait loci(pQTLs)...AIM:To explore whether plasma proteins serve as potential therapeutic targets for primary open angle glaucoma(POAG)based on a Mendelian randomization(MR)study.METHODS:Large-scale protein quantitative trait loci(pQTLs)data from the Icelandic deCODE database and two large POAG Genome-Wide Association Study(GWAS)summary datasets were used in this study.Causal associations between plasma proteins and POAG were identified using summary-data-based MR(SMR)analysis and the heterogeneity in dependent instruments(HEIDI)test.Colocalization analysis was then conducted to assess the genetic associations between these two factors.Phenotype-wide MR analysis was performed to validate protein targets as potential drug targets and to evaluate potential side effects.Finally,protein-protein interactions(PPI)were studied,and the Drug-Gene Interaction Database(DGIDb)was used to identify associations between drugs and the identified proteins.RESULTS:Four proteins(SVEP1,TMEM190,ROBO1,and ENPP5)were identified as potential drug targets in this study.Phenome-wide MR analysis showed that SVEP1,ROBO1,and ENPP5 were not associated with adverse effects,while TMEM190 was linked to nerve root and plexus disorders,as well as subarachnoid hemorrhage.Ticagrelor was suggested as a potential new drug for the treatment of glaucoma by regulating SVEP1.CONCLUSION:Four plasma proteins—SVEP1,TMEM190,ROBO1,and ENPP5—are identified as potential therapeutic targets for POAG through an MR approach.Phenome-wide MR analysis reveals that SVEP1,ROBO1,and ENPP5 are not associated with adverse effects,while TMEM190 is linked to nerve root and plexus disorders,as well as subarachnoid hemorrhage.Ticagrelor is proposed as a potential therapeutic drug for glaucoma by regulating SVEP1.These findings highlight the potential of plasma proteins as drug targets for POAG and provide valuable insights for further research.展开更多
In the existing impact time control guidance (ITCG) laws for moving-targets, the effects of time-varying velocity caused by aerodynamics and gravity cannot be effectively con-sidered. Therefore, an ITCG with field-of-...In the existing impact time control guidance (ITCG) laws for moving-targets, the effects of time-varying velocity caused by aerodynamics and gravity cannot be effectively con-sidered. Therefore, an ITCG with field-of-view (FOV) constraints based on biased proportional navigation guidance (PNG) is developed in this paper. The remaining flight time (time-to-go) estimation method is derived considering aerodynamic force and gravity. The number of differential equations is reduced and the integration step is increased by changing the integral variable, which makes it possible to obtain time-to-go through integration. An impact time controller with FOV constraints is proposed by analyzing the influence of the biased term on time-to-go and FOV constraint. Then, numerical simulations are performed to verify the correctness and superiority of the method.展开更多
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy.Substantial therapeutic benefits in cancer therapy have been achieved by the integrat...The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy.Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies.Human epidermal growth factor receptor,hormone receptors,and angiogenesis factors are among the established therapies in tumor reduction and managing side effects.Novel targeted therapies like KRAS G12C,Claudin-18 isoform 2(CLDN18.2),Trophoblast cell-surface antigen 2(TROP2),and epigenetic regulators emphasize their promise in advancing precision medicine.However,in many cases,the resistance mechanisms associated with these interventions render them ineffective in carrying out their functions.The purpose of this review is to provide a comprehensive and up-to-date examination of both established and emerging drug targets and mechanisms of treatment resistance in oncology.This review seeks to elucidate recent advancements,address persisting challenges,and explore opportunities for innovative developments in cancer target research.Additionally,it explores the growing role of artificial intelligence in reshaping cancer drug discovery and development frameworks as potential avenues for future research.In conclusion,innovative approaches in oncology,supported by pharmacological research,ongoing clinical trials,molecular biosciences,and artificial intelligence,are poised to significantly transform cancer treatment.展开更多
Diabetes involves multi-organ complications that seriously threaten human life and health,and has become a major public health problem of global concern.Unfortunately,clinical management strategies for diabetic compli...Diabetes involves multi-organ complications that seriously threaten human life and health,and has become a major public health problem of global concern.Unfortunately,clinical management strategies for diabetic complications are still in their“infancy”,restricted by a limited understanding of their complex pathological mechanism.As is well established,lipid metabolism disorder is the characteristic pathological factors of diabetes,but the detailed molecular mechanisms driving the progression of multi-organ complications remain obscure.Protein S-acylation(often referred to as S-palmitoylation)is a reversible lipid modification that reversibly binds fatty acids to protein-specific cysteine(Cys)residues through palmitoyl acyl transferases(PATs,also known as DHHCs)and deacylation enzymes,which is involved in the pathological progression of a variety of complex diseases such as cancer,neurological disorders and metabolic syndrome.Notably,recent studies have shown that protein S-acylation drives the progression of diabetes and its multiple complications,and targeted intervention in the protein S-acylation process significantly alleviates the progression of diabetes and its complications,suggesting that protein S-acylation may be a common pathological link and intervention target of diabetes complications.Therefore,this review systematically comprehends the contribution of protein S-acylation to the progression of diabetes and its complications,summarizes the influence of the diabetic environment on S-acylation related enzymes,as well as providing an in-depth analysis of current drugs,measures,and challenges in targeting S-acylation.Finally,the accessibility of targeting protein S-acylation to prevent diabetes and its complications and the focus of future in-depth studies are envisioned,with a view to providing comprehensive and in-depth references and rationale for future novel strategies targeting protein S-acylation to prevent and treat diabetes and its multi-organ complications.展开更多
We read with great interest Deng et al.’s study 1 comparing sextant(6-core)and 12-core systematic biopsy in theMRI-targeted era,which valuably challenges the“more cores=higher accuracy”dogma by proposing a precisio...We read with great interest Deng et al.’s study 1 comparing sextant(6-core)and 12-core systematic biopsy in theMRI-targeted era,which valuably challenges the“more cores=higher accuracy”dogma by proposing a precision sampling strategy based on prostate cancer’s spatial distribution,aligning with personalized diagnosis trends.展开更多
Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-through...Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.展开更多
In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquiti...In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquitin ligase ligand,and a linker connecting these ligands.By harnessing the cell’s intrinsic ubiquitin-proteasome system(UPS),they promote the ubiquitination of specific target proteins,leading to their degradation and therapeutic effects.PROTACs show exceptional promise in targeting conventional“undruggable”targets compared to traditional small-molecule inhibitors.This review provides an overview of PROTACs,including their molecular mechanism of action,therapeutic benefits,development history,key design aspects,current research and development challenges,and future trends in nextgeneration PROTAC technology.展开更多
Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis....Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis.Herein,the targeted theranostic platform of cysteine-modified gold nanodots-sulfhydrated luteinizing hormone releasing hormone(CGN-SLR)nanosystem was designed for target recognition and precise dual-mode imaging-guided photothermal therapy(PTT)against TNBC.On the one hand,the CGN-SLR nanosystem can serve as an ideal targeting fluorescent probe and computed tomography(CT)enhancer to facilitate the accurate diagnosis and surgical guidance of TNBC.On the other hand,the CGN-SLR nanosystem with great targeting and PTT ability can significantly inhibit the growth of TNBC,without causing harm to normal tissues and healthy organs.It provides an effective strategy for the diagnosis and treatment of TNBC through the rational design of multifunctional nanoplatform with target recognition,multiple imaging guidance/monitoring,and high-efficiency PTT.展开更多
The published article titled“MicroRNA-133b Inhibits Proliferation,Cellular Migration,and Invasion via Targeting LASP1 in Hepatocarcinoma Cells”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1269–1282.
Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-202 Promotes Cell Apoptosis in Esophageal Squamous Cell Carcinoma by Targeting HSF2”has been retracted from Oncology Rese...Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-202 Promotes Cell Apoptosis in Esophageal Squamous Cell Carcinoma by Targeting HSF2”has been retracted from Oncology Research,Vol.25,No.2,2017,pp.215-223.DOI:10.3727/096504016X14732772150541 URL:https://www.techscience.com/or/v25n2/56800.展开更多
Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through...Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.展开更多
Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-126-5p Restoration Promotes Cell Apoptosis in Cervical Cancer by Targeting Bcl2l2”has been retracted from Oncology Resear...Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-126-5p Restoration Promotes Cell Apoptosis in Cervical Cancer by Targeting Bcl2l2”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.463-470.DOI:10.3727/096504016X14685034103879 URL:https://www.techscience.com/or/v25n4/56826.展开更多
Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensiv...Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.展开更多
Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted thera...Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted therapy emerges as a paramount approach to address this substantial unmet clinical need,owing to its precise tumor targeting capabilities and potential for mitigating tumor progression risks.Drug conjugates are in high demand for targeted therapy due to their unique ligand specificity and potent cytotoxicity,thereby significantly enhancing therapeutic efficacy and reducing the incidence of adverse effects.Therefore,as a burgeoning field in biomedical research,it is timely to outline the latest advances in drug conjugates-driven cancer treatment.Herein,we aim to present the emerging breakthroughs in this exciting field at the intersection of target ligands,linkers,payloads,and cancer treatments.This review focuses on several drug conjugates-related strategies,including antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),small molecule-drug conjugates(SMDCs),aptamer-drug conjugates(ApDCs)and radionuclide-drug conjugates(RDCs).Finally,we discuss the fundamentals behind drug conjugate-based anticancer therapeutics,along with their inherent advantages and associated challenges,as well as recent research advances.展开更多
Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of ...Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.展开更多
基金Supported by the National Natural Science Foundation of China under Grant Nos 11421505 and 11220101005the National Basic Research Program of China under Grant No 2014CB845401
文摘The ratio of the number of emitted pions from the target side to that from the projectile side at target rapidity within the reaction plane is investigated for the study of the pion dynamics with an isospin-dependent quantum molecular dynamic model. The results show that high-energy pions are emitted preferentially towards the target side and, therefore, they are freezed out at the early stage of the collision. By contrast, low-energy pions are emitted predominantly in the opposite direction, which means that they are emitted in a later stage. This argument is based on the shadowing effect caused by the interaction of pions with the spectator matter in peripheral collisions at target or projectile rapidities. This phenomenon disappears in the central collision or at midrapidity due to the weaker shadowing effect. The calculated ratios are also compared with the experimental data.
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
基金support from the National Natural Science Foundation of China(Grant Nos.:U21A20407 and 81973467).
文摘Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.
文摘Using the back skin of the mice as the test object,UPLC was used to determine the retention rate of Glabridin(GLA)in the skin and subcutaneous fat pf mice with different dosage forms and different administration times,and to investigate the transdermal absorption effect of liquid crystal cream.The experimental results showed that the 0.5,1,2,4,6 and 8h skin retention rates of GLA in the liquid crystal cream group were 1.67,0.79,1.73,1.47,1.17 and 1.15 times higher than those of the ordinary cream group under the same dosage of administration,respectively.The 0.5,1,2,4,6 and 8 h fat retention rates of GLA in the normal cream group were 0.86,1.87,1.37,1.20,1.35 and 1.19 times higher than those in the liquid crystal group,respectively.Liquid crystal cream can significantly improve the skin retention of GLA,with certain slow and controlled release,and possesses certain skin targeting properties.
基金Supported by the National Natural Science Foundation of China(No.81770920)Open Project of State Key Laboratory of Ophthalmology(No.303060202400383).
文摘AIM:To explore whether plasma proteins serve as potential therapeutic targets for primary open angle glaucoma(POAG)based on a Mendelian randomization(MR)study.METHODS:Large-scale protein quantitative trait loci(pQTLs)data from the Icelandic deCODE database and two large POAG Genome-Wide Association Study(GWAS)summary datasets were used in this study.Causal associations between plasma proteins and POAG were identified using summary-data-based MR(SMR)analysis and the heterogeneity in dependent instruments(HEIDI)test.Colocalization analysis was then conducted to assess the genetic associations between these two factors.Phenotype-wide MR analysis was performed to validate protein targets as potential drug targets and to evaluate potential side effects.Finally,protein-protein interactions(PPI)were studied,and the Drug-Gene Interaction Database(DGIDb)was used to identify associations between drugs and the identified proteins.RESULTS:Four proteins(SVEP1,TMEM190,ROBO1,and ENPP5)were identified as potential drug targets in this study.Phenome-wide MR analysis showed that SVEP1,ROBO1,and ENPP5 were not associated with adverse effects,while TMEM190 was linked to nerve root and plexus disorders,as well as subarachnoid hemorrhage.Ticagrelor was suggested as a potential new drug for the treatment of glaucoma by regulating SVEP1.CONCLUSION:Four plasma proteins—SVEP1,TMEM190,ROBO1,and ENPP5—are identified as potential therapeutic targets for POAG through an MR approach.Phenome-wide MR analysis reveals that SVEP1,ROBO1,and ENPP5 are not associated with adverse effects,while TMEM190 is linked to nerve root and plexus disorders,as well as subarachnoid hemorrhage.Ticagrelor is proposed as a potential therapeutic drug for glaucoma by regulating SVEP1.These findings highlight the potential of plasma proteins as drug targets for POAG and provide valuable insights for further research.
基金supported by the National Natural Science Foundation of China(U21B2028).
文摘In the existing impact time control guidance (ITCG) laws for moving-targets, the effects of time-varying velocity caused by aerodynamics and gravity cannot be effectively con-sidered. Therefore, an ITCG with field-of-view (FOV) constraints based on biased proportional navigation guidance (PNG) is developed in this paper. The remaining flight time (time-to-go) estimation method is derived considering aerodynamic force and gravity. The number of differential equations is reduced and the integration step is increased by changing the integral variable, which makes it possible to obtain time-to-go through integration. An impact time controller with FOV constraints is proposed by analyzing the influence of the biased term on time-to-go and FOV constraint. Then, numerical simulations are performed to verify the correctness and superiority of the method.
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
文摘The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy.Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies.Human epidermal growth factor receptor,hormone receptors,and angiogenesis factors are among the established therapies in tumor reduction and managing side effects.Novel targeted therapies like KRAS G12C,Claudin-18 isoform 2(CLDN18.2),Trophoblast cell-surface antigen 2(TROP2),and epigenetic regulators emphasize their promise in advancing precision medicine.However,in many cases,the resistance mechanisms associated with these interventions render them ineffective in carrying out their functions.The purpose of this review is to provide a comprehensive and up-to-date examination of both established and emerging drug targets and mechanisms of treatment resistance in oncology.This review seeks to elucidate recent advancements,address persisting challenges,and explore opportunities for innovative developments in cancer target research.Additionally,it explores the growing role of artificial intelligence in reshaping cancer drug discovery and development frameworks as potential avenues for future research.In conclusion,innovative approaches in oncology,supported by pharmacological research,ongoing clinical trials,molecular biosciences,and artificial intelligence,are poised to significantly transform cancer treatment.
基金supported by National Natural Science Foundation of China(No.82304909)National Natural Science Foundation of China(No.82174112)Tianjin Science and Technology Innovation Base Construction(No.24ZYJDSY00280).
文摘Diabetes involves multi-organ complications that seriously threaten human life and health,and has become a major public health problem of global concern.Unfortunately,clinical management strategies for diabetic complications are still in their“infancy”,restricted by a limited understanding of their complex pathological mechanism.As is well established,lipid metabolism disorder is the characteristic pathological factors of diabetes,but the detailed molecular mechanisms driving the progression of multi-organ complications remain obscure.Protein S-acylation(often referred to as S-palmitoylation)is a reversible lipid modification that reversibly binds fatty acids to protein-specific cysteine(Cys)residues through palmitoyl acyl transferases(PATs,also known as DHHCs)and deacylation enzymes,which is involved in the pathological progression of a variety of complex diseases such as cancer,neurological disorders and metabolic syndrome.Notably,recent studies have shown that protein S-acylation drives the progression of diabetes and its multiple complications,and targeted intervention in the protein S-acylation process significantly alleviates the progression of diabetes and its complications,suggesting that protein S-acylation may be a common pathological link and intervention target of diabetes complications.Therefore,this review systematically comprehends the contribution of protein S-acylation to the progression of diabetes and its complications,summarizes the influence of the diabetic environment on S-acylation related enzymes,as well as providing an in-depth analysis of current drugs,measures,and challenges in targeting S-acylation.Finally,the accessibility of targeting protein S-acylation to prevent diabetes and its complications and the focus of future in-depth studies are envisioned,with a view to providing comprehensive and in-depth references and rationale for future novel strategies targeting protein S-acylation to prevent and treat diabetes and its multi-organ complications.
文摘We read with great interest Deng et al.’s study 1 comparing sextant(6-core)and 12-core systematic biopsy in theMRI-targeted era,which valuably challenges the“more cores=higher accuracy”dogma by proposing a precision sampling strategy based on prostate cancer’s spatial distribution,aligning with personalized diagnosis trends.
基金the Deanship of Research and Graduate Studies at King Khalid University,KSA,for funding this work through the Large Research Project under grant number RGP2/164/46.
文摘Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.
文摘In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquitin ligase ligand,and a linker connecting these ligands.By harnessing the cell’s intrinsic ubiquitin-proteasome system(UPS),they promote the ubiquitination of specific target proteins,leading to their degradation and therapeutic effects.PROTACs show exceptional promise in targeting conventional“undruggable”targets compared to traditional small-molecule inhibitors.This review provides an overview of PROTACs,including their molecular mechanism of action,therapeutic benefits,development history,key design aspects,current research and development challenges,and future trends in nextgeneration PROTAC technology.
基金supported by the Natural Science Foundation of Jilin Province(No.SKL202302002).
文摘Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis.Herein,the targeted theranostic platform of cysteine-modified gold nanodots-sulfhydrated luteinizing hormone releasing hormone(CGN-SLR)nanosystem was designed for target recognition and precise dual-mode imaging-guided photothermal therapy(PTT)against TNBC.On the one hand,the CGN-SLR nanosystem can serve as an ideal targeting fluorescent probe and computed tomography(CT)enhancer to facilitate the accurate diagnosis and surgical guidance of TNBC.On the other hand,the CGN-SLR nanosystem with great targeting and PTT ability can significantly inhibit the growth of TNBC,without causing harm to normal tissues and healthy organs.It provides an effective strategy for the diagnosis and treatment of TNBC through the rational design of multifunctional nanoplatform with target recognition,multiple imaging guidance/monitoring,and high-efficiency PTT.
文摘The published article titled“MicroRNA-133b Inhibits Proliferation,Cellular Migration,and Invasion via Targeting LASP1 in Hepatocarcinoma Cells”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1269–1282.
文摘Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-202 Promotes Cell Apoptosis in Esophageal Squamous Cell Carcinoma by Targeting HSF2”has been retracted from Oncology Research,Vol.25,No.2,2017,pp.215-223.DOI:10.3727/096504016X14732772150541 URL:https://www.techscience.com/or/v25n2/56800.
基金supported by grants from the Fundamental Research Funds for the Central Universities(No.2025ZFJH03)the Central Guidance Fund for Local Science and Technology Development(No.2024ZY01054)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-045).
文摘Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.
文摘Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-126-5p Restoration Promotes Cell Apoptosis in Cervical Cancer by Targeting Bcl2l2”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.463-470.DOI:10.3727/096504016X14685034103879 URL:https://www.techscience.com/or/v25n4/56826.
基金supported by a grant from the Dalian Science and Technology Innovation Fund Program(No.2024JJ13PT070)United Foundation for Dalian Institute of Chemical Physics,Chinese Academy of Sciences and the Second Hospital of Dalian Medical University(No.DMU-2&DICP UN202410)Dalian Life and Health Field Guidance Program Project(No.2024ZDJH01PT084).
文摘Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.
基金the Project of China-Japan Joint International Laboratory of Advanced Drug Delivery System Research and Translation of Liaoning Province(No.2024JH2/102100007)the open fund of National Key Laboratory of Advanced DrugFormulations for Overcoming Delivery Barriers(No.2024-KFB-003)+1 种基金the National Natural Science Foundation of China(No.82104109)Scientific Research Project of Liaoning Department of Education(No.LJ212410163045).
文摘Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted therapy emerges as a paramount approach to address this substantial unmet clinical need,owing to its precise tumor targeting capabilities and potential for mitigating tumor progression risks.Drug conjugates are in high demand for targeted therapy due to their unique ligand specificity and potent cytotoxicity,thereby significantly enhancing therapeutic efficacy and reducing the incidence of adverse effects.Therefore,as a burgeoning field in biomedical research,it is timely to outline the latest advances in drug conjugates-driven cancer treatment.Herein,we aim to present the emerging breakthroughs in this exciting field at the intersection of target ligands,linkers,payloads,and cancer treatments.This review focuses on several drug conjugates-related strategies,including antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),small molecule-drug conjugates(SMDCs),aptamer-drug conjugates(ApDCs)and radionuclide-drug conjugates(RDCs).Finally,we discuss the fundamentals behind drug conjugate-based anticancer therapeutics,along with their inherent advantages and associated challenges,as well as recent research advances.
文摘Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.
