Macrophages are innate immune cells that are ubiquitously distributed throughout the vertebrate body.Macrophages orchestrate sophisticated processes in development,homeostasis,immunity,and disease1.Macrophages residin...Macrophages are innate immune cells that are ubiquitously distributed throughout the vertebrate body.Macrophages orchestrate sophisticated processes in development,homeostasis,immunity,and disease1.Macrophages residing in tumor tissues are commonly known as tumor-associated macrophages(TAMs)and promote or inhibit tumor growth depending on the activation state2.展开更多
Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host d...Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host disease(GVHD)and complications of immunosuppressive drugs after allo-HSCT are the main causes of non-relapse mortality and a poor quality of life.In addition,GVHD and infusion-induced toxicity still occur with donor lymphocyte infusions(DLIs)and chimeric antigen receptor(CAR)T-cell therapy.Because of the special immune tolerance characteristics and anti-tumor ability of universal immune cells,universal immune cell therapy may strongly reduce GVHD,while simultaneously reducing tumor burden.Nevertheless,widespread application of universal immune cell therapy is mainly restricted by poor expansion and persistence efficacy.Many strategies have been applied to improve universal immune cell proliferation and persistence efficacy,including the use of universal cell lines,signaling regulation and CAR technology.In this review we have summarized current advances in universal immune cell therapy for hematologic malignancies with a discussion of future perspectives.展开更多
Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell ac...Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.展开更多
Cancer stem cells(CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the ex...Cancer stem cells(CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the existence of CSCs in various types of cancers and suggested that CSCs differentiate into diverse lineage cells that contribute to tumor progression. We may be able to overcome the limitations of cancer treatment with a comprehensive understanding of the biological features and mechanisms underlying therapeutic resistance in CSCs. This review provides an overview of the properties, biomarkers, and mechanisms of resistance shown by CSCs. Recent findings on metabolic features, especially fatty acid metabolism and ferroptosis in CSCs, are highlighted, along with promising targeting strategies. Targeting CSCs is a potential treatment plan to conquer cancer and prevent resistance and relapse in cancer treatment.展开更多
The clearance of apoptotic cell debris,containing professional phagocytosis and non-professional phagocytosis,is essential for maintaining the homeostasis of healthy tissues.Here,we discovered that endothelial cells c...The clearance of apoptotic cell debris,containing professional phagocytosis and non-professional phagocytosis,is essential for maintaining the homeostasis of healthy tissues.Here,we discovered that endothelial cells could engulf apoptotic cell debris in atherosclerotic plaque.Single-cell RNA sequencing(RNA-seq)has revealed a unique endothelial cell subpopulation in atherosclerosis,which was strongly associated with vascular injury-related pathways.Moreover,integrated analysis of three vascular injury-related RNA-seq datasets showed that the expression of scavenger receptor class B type 1(SR-B1)was up-regulated and specifically enriched in the phagocytosis pathway under vascular injury circumstances.Single-cell RNA-seq and bulk RNA-seq indicate that SR-B1 was highly expressed in a unique endothelial cell subpopulation of mouse aorta and strongly associated with the reorganization of cellular adherent junctions and cytoskeleton which were necessary for phagocytosis.Furthermore,SR-B1 was strongly required for endothelial cells to engulf apoptotic cell debris in atherosclerotic plaque of both mouse and human aorta.Overall,this study demonstrated that apoptotic cell debris could be engulfed by endothelial cells through SR-B1 and associated with the reorganization of cellular adherent junctions and cytoskeleton.展开更多
Although neuroelectrochemical sensing technology offers unique benefits for neuroscience research,its application is limited by substantial interference in complex brain environments while ensuring biosafety requireme...Although neuroelectrochemical sensing technology offers unique benefits for neuroscience research,its application is limited by substantial interference in complex brain environments while ensuring biosafety requirements.In this study,we introduced poly(3-hexylthiophene)(P3HT)and nitrogen-doped multiwalled carbon nanotubes(N-MWCNTs)to construct a composite membrane-modified carbon fiber microelectrode(CFME/P3HT-N-MWCNTs)for ascorbic acid(AA)detection.The microelectrode presented good linearity,selectivity,stability,antifouling,and biocompatibility and exhibited great performance for application in neuroelectrochemical sensing.Subsequently,we applied CFME/P3HT-N-MWCNTs to monitor AA release from in vitro nerve cells,ex vivo brain slices,and in vivo living rat brains and determined that glutamate can induce cell edema and AA release.We also found that glutamate activated the N-methyl-d-aspartic acid receptor,which enhanced Na^(+) and Cl^(−) inflow to induce osmotic stress,resulting in cytotoxic edema and ultimately AA release.This study is the first to observe the process of glutamate-induced brain cytotoxic edema with AA release and to reveal the mechanism.Our work can benefit the application of P3HT in in vivo implant microelectrode construction to monitor neurochemicals,understand the molecular basis of nervous system diseases,and discover certain biomarkers of brain diseases.展开更多
Objectives:To examine the 16-year developmental history,research hotspots,and emerging trends of zinc-based biodegradable metallic materials from the perspective of structural and temporal dynamics.Methods:The literat...Objectives:To examine the 16-year developmental history,research hotspots,and emerging trends of zinc-based biodegradable metallic materials from the perspective of structural and temporal dynamics.Methods:The literature on zinc-based biodegradable metallic materials in WoSCC was searched.Historical characteristics,the evolution of active topics and development trends in the field of zinc-based biodegradable metallic materials were analyzed using the bibliometric tools CiteSpace and HistCite.Results:Over the past 16 years,the field of zinc-based biodegradable metal materials has remained in a hotspot stage,with extensive scientific collaboration.In addition,there are 45 subject categories and 51 keywords in different research periods,and 80 papers experience citation bursts.Keyword clustering anchored 3 emerging research subfields,namely,#1 plastic deformation#4 additive manufacturing#5 surface modification.The keyword alluvial map shows that the longest-lasting research concepts in the field are mechanical property,microstructure,corrosion behavior,etc.,and emerging keywords are additive manufacturing,surface modification,dynamic recrystallization,etc.The most recent research on reference clustering has six subfields.Namely,#0 microstructure,#2 sem,#3 additive manufacturing,#4 laser powder bed fusion,#5 implant,and#7 Zn-1Mg.Conclusion:The results of the bibliometric study provide the current status and trends of research on zinc-based biodegradable metallic materials,which can help researchers identify hot spots and explore new research directions in the field.展开更多
Dysfunction of CD8^(+)T cells in the tumor microenvironment(TME)contributes to tumor immune escape and immunotherapy tolerance.The effects of hormones such as leptin,steroid hormones,and glucocorticoids on T cell func...Dysfunction of CD8^(+)T cells in the tumor microenvironment(TME)contributes to tumor immune escape and immunotherapy tolerance.The effects of hormones such as leptin,steroid hormones,and glucocorticoids on T cell function have been reported previously.However,the mechanism underlying thyroid-stimulating hormone(TSH)/thyroid-stimulating hormone receptor(TSHR)signaling in CD8^(+)T cell exhaustion and tumor immune evasion remain poorly understood.This study was aimed at investigating the effects of TSH/TSHR signaling on the function of CD8^(+)T cells and immune evasion in colorectal cancer(CRC).Methods:TSHR expression levels in CD8^(+)T cells were assessed with immunofluorescence and flow cytometry.Functional investigations involved manipulation of TSHR expression in cellular and mouse models to study its role in CD8^(+)T cells.Mechanistic insights were mainly gained through RNAsequencing,Western blotting,chromatin immunoprecipitation and luciferase activity assay.Immunofluorescence,flow cytometry and Western blotting were used to investigate the source of TSH and TSHR in CRC tissues.Results:TSHR was highly expressed in cancer cells and CD8^(+)T cells in CRC tissues.TSH/TSHR signaling was identified as the intrinsic pathway promoting CD8^(+)T cell exhaustion.Conditional deletion of TSHR in CD8^(+)tumorinfiltrating lymphocytes(TILs)improved effector differentiation and suppressed the expression of immune checkpoint receptors such as programmed cell death 1(PD-1)and hepatitis A virus cellular receptor 2(HAVCR2 or TIM3)through the protein kinase A(PKA)/cAMP-response element binding protein(CREB)signaling pathway.CRC cells secreted TSHR via exosomes to increase the TSHR level in CD8^(+)T cells,resulting in immunosuppression in the TME.Myeloid-derived suppressor cells(MDSCs)was the main source of TSH within the TME.Low expression of TSHR in CRC was a predictor of immunotherapy response.Conclusions:The present findings highlighted the role of endogenous TSH/TSHR signaling in CD8^(+)T cell exhaustion and immune evasion in CRC.TSHR may be suitable as a predictive and therapeutic biomarker in CRC immunotherapy.展开更多
High myopia(HM)is the primary cause of blindness,with the microstructural organization and composition of collagenous fibers in the cornea and sclera playing a crucial role in the biomechanical behavior of these tissu...High myopia(HM)is the primary cause of blindness,with the microstructural organization and composition of collagenous fibers in the cornea and sclera playing a crucial role in the biomechanical behavior of these tissues.In a previously reported myopic linkage region,MYP5(17q21-22),a potential candidate gene,LRRC46(c.C235T,p.Q79X),was identified in a large Han Chinese pedigree.LRRC46 is expressed in various eye tissues in humans and mice,including the retina,cornea,and sclera.In subsequent cell experiments,the mutation(c.C235T)decreased the expression of LRRC46 protein in human corneal epithelial cells(HCE-T).Further investigation revealed that Lrrc46^(-/-)mice(KO)exhibited a classical myopia phenotype.The thickness of the cornea and sclera in KO mice became thinner and more pronounced with age,the activity of limbal stem cells decreased,and microstructural changes were observed in the fibroblasts of the sclera and cornea.We performed RNA-seq on scleral and corneal tissues of KO and normal control wild-type(WT)mice,which indicated a significant downregulation of the collagen synthesis-related pathway(extracellular matrix,ECM)in KO mice.Subsequent in vitro studies further indicated that LRRC46,a member of the important LRR protein family,primarily affected the formation of collagens.This study suggested that LRRC46 is a novel candidate gene for HM,influencing collagen protein VⅢ(Col8a1)formation in the eye and gradually altering the biomechanical structure of the cornea and sclera,thereby promoting the occurrence and development of HM.展开更多
The proper transfer of genetic information from DNA to RNA to protein is essential for cell-fate control,development,and health.Methylation of DNA,RNAs,histones,and non-histone proteins is a reversible post-synthesis ...The proper transfer of genetic information from DNA to RNA to protein is essential for cell-fate control,development,and health.Methylation of DNA,RNAs,histones,and non-histone proteins is a reversible post-synthesis modification that finetunes gene expression and function in diverse physiological processes.Aberrant methylation caused by genetic mutations or environmental stimuli promotes various diseases and accelerates aging,necessitating the development of therapies to correct the disease-driver methylation imbalance.In this Review,we summarize the operating system of methylation across the central dogma,which includes writers,erasers,readers,and reader-independent outputs.We then discuss how dysregulation of the system contributes to neurological disorders,cancer,and aging.Current small-molecule compounds that target the modifiers show modest success in certain cancers.The methylome-wide action and lack of specificity lead to undesirable biological effects and cytotoxicity,limiting their therapeutic application,especially for diseases with a monogenic cause or different directions of methylation changes.Emerging tools capable of site-specific methylation manipulation hold great promise to solve this dilemma.With the refinement of delivery vehicles,these new tools are well positioned to advance the basic research and clinical translation of the methylation field.展开更多
Background: Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects mi...Background: Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown. Methods: Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca^(2+)-related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance. Results: Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca ^(2+ )is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments. Conclusions: Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.展开更多
Purpose:This review aims to explore the history,research hotspots,and emerging trends of drug-eluting stents(DES)in the last two decades from the perspective of structural and temporal dynamics.Methods:Publications on...Purpose:This review aims to explore the history,research hotspots,and emerging trends of drug-eluting stents(DES)in the last two decades from the perspective of structural and temporal dynamics.Methods:Publications on DES were retrieved from WoSCC.The bibliometric tools including CiteSpace and HistCite were used to identify the historical features,the evolution of active topics,and emerging trends on the DES field.Results:In the last 20 years,the field of DES is still in the hot phase and there is a wide range of extensive scientific collaborations.In addition,active topics emerge in different periods,as evidenced by a total of 41 disciplines,511 keywords,and 1377 papers with citation bursts.Keyword clustering anchored five emerging research subfields,namely#0 dual antiplatelet therapy,#3 drug-coated balloon,#4 bifurcation,5#rotational atherectomy,and 6#quantitative flow ratio.The keyword alluvial map shows that the most persistent research concepts in this field are thrombosis,restenosis,etc.,and the emerging keywords are paclitaxel eluting balloon,coated balloon,drug-eluting balloon,etc.There are 7 recent research subfields anchored by reference clustering,namely#2 dual antiplatelet therapy,#4 drug-coated balloon,#5 peripheral artery disease,#8 fractional flow reserve,#10 bioresorbable vascular scaffold,#13 intravascular ultrasound,#14 biodegradable polymer.Conclusion:The findings based on the bibliometric studies provide the current status and trends in DES research and may help researchers to identify hot topics and explore new research directions in this field.展开更多
LncMIR31HG acts as a host gene for miR-31,also known as LncHIFCAR(long non-coding HIF-1 co-activating RNA),whose deregulation has been reported to promote the development of various human cancers,including lung cancer...LncMIR31HG acts as a host gene for miR-31,also known as LncHIFCAR(long non-coding HIF-1 co-activating RNA),whose deregulation has been reported to promote the development of various human cancers,including lung cancer,colorectal cancer,etc.1,2 However,the biological functions and molecular mechanisms of MIR31HG in gastric cancer are unclear.展开更多
Multiple signal strategies remarkably improve the accuracy and efficiency of electrochemiluminescence(ECL)immunoassays,but the lack of potential-resolved luminophore pairs and chemical cross talk hinders their develop...Multiple signal strategies remarkably improve the accuracy and efficiency of electrochemiluminescence(ECL)immunoassays,but the lack of potential-resolved luminophore pairs and chemical cross talk hinders their development.In this study,we synthesized a series of gold nanoparticles(AuNPs)/reduced graphene oxide(Au/rGO)composites as adjustable oxygen reduction reaction and oxygen evolution reaction catalysts to promote and modulate tris(2,2′-bipyridine)ruthenium(II)(Ru(bpy)_(3)^(2+))’s multisignal luminescence.With the increase in the diameter of AuNPs(3 to 30 nm),their ability to promote Ru(bpy)_(3)^(2+)’s anodic ECL was first impaired and then strengthened,and cathodic ECL was first enhanced and then weakened.Au/rGOs with medium-small and medium-large AuNP diameters remarkably increased Ru(bpy)_(3)^(2+)’s cathodic and anodic luminescence,respectively.Notably,the stimulation effects of Au/rGOs were superior to those of most existing Ru(bpy)_(3)^(2+)co-reactants.Moreover,we proposed a novel ratiometric immunosensor construction strategy using Ru(bpy)_(3)^(2+)’s luminescence promoter rather than luminophores as tags of antibodies to achieve signal resolution.This method avoids signal cross talk between luminophores and their respective co-reactants,which achieved a good linear range of 10−7 to 10−1 ng/ml and a limit of detection of 0.33 fg/ml for detecting carcinoembryonic antigen.This study addresses the previous scarcity of the macromolecular co-reactants of Ru(bpy)_(3)^(2+),broadening its application in biomaterial detection.Furthermore,the systematic clarification of the detailed mechanisms for converting the potential-resolved luminescence of Ru(bpy)_(3)^(2+)could facilitate an in-depth understanding of the ECL process and should inspire new designs of Ru(bpy)_(3)^(2+)luminescence enhancers or applications of Au/rGOs to other luminophores.This work removes some impediments to the development of multisignal ECL biodetection systems and provides vitality into their widespread applications.展开更多
Nanoparticles(NPs)hold tremendous targeting potential in cardiovascular disease and regenerative medicine,and exciting clinical applications are coming into light.Vascular endothelial cells(ECs)exposure to different m...Nanoparticles(NPs)hold tremendous targeting potential in cardiovascular disease and regenerative medicine,and exciting clinical applications are coming into light.Vascular endothelial cells(ECs)exposure to different magnitudes and patterns of shear stress(SS)generated by blood flow could engulf NPs in the blood.However,an unclear understanding of the role of SS on NP uptake is hindering the progress in improving the targeting of NP therapies.Here,the temporal and spatial distribution of SS in vascular ECs and the effect of different SS on NP uptake in ECs are highlighted.The mechanism of SS affecting NP uptake through regulating the cellular ROS level,endothelial glycocalyx and membrane fluidity is summarized,and the molecules containing clathrin and caveolin in the engulfment process are elucidated.SS targeting NPs are expected to overcome the current bottlenecks and change the field of targeting nanomedicine.This assessment on how SS affects the cell uptake of NPs and the marginalization of NPs in blood vessels could guide future research in cell biology and vascular targeting drugs.展开更多
Adoptive cell therapy(ACT)has emerged with remarkable efficacies for tumor immunotherapy.Chimeric antigen receptor(CAR)T cell therapy,as one of most promising ACTs,has achieved prominent effects in treating malignant ...Adoptive cell therapy(ACT)has emerged with remarkable efficacies for tumor immunotherapy.Chimeric antigen receptor(CAR)T cell therapy,as one of most promising ACTs,has achieved prominent effects in treating malignant hematological tumors.However,the insufficient killing activity and limited persistence of T cells in the immunosuppressive tumor microenvironment limit the further application of ACTs for cancer patients.Many studies have focused on improving cytotoxicity and persistence of T cells to achieve improved therapeutic effects.In this study,we explored the potential function in ACT of ginsenoside Rg1,the main pharmacologically active component of ginseng.We introduced Rg1 during the in vitro activation and expansion phase of T cells,and found that Rg1 treatment upregulated two T cell activation markers,CD69 and CD25,while promoting T cell differentiation towards a mature state.Transcriptome sequencing revealed that Rg1 influenced T cell metabolic reprogramming by strengthening mitochondrial biosynthesis.When co-cultured with tumor cells,Rg1-treated T cells showed stronger cytotoxicity than untreated cells.Moreover,adding Rg1 to the culture endowed CAR-T cells with enhanced anti-tumor efficacy.This study suggests that ginsenoside Rg1 provides a potential approach for improving the anti-tumor efficacy of ACT by enhancing T cell effector functions.展开更多
The most common socioeconomic healthcare issues in clinical are burns,surgical incisions and other skin injuries.Skin lesion healing can be achieved with nanomedicines and other drug application techniques.This study ...The most common socioeconomic healthcare issues in clinical are burns,surgical incisions and other skin injuries.Skin lesion healing can be achieved with nanomedicines and other drug application techniques.This study developed a nano-spray based on cross-linked amorphous calcium peroxide(CaO_(2))nanoparticles of polyacrylic acid(PAA)for treating skin wounds(PAA-CaO_(2)nanoparticles).CaO_(2)serves as a‘drug’precursor,steadily and continuously releasing calcium ions(Ca^(2+))and hydrogen peroxide(H_(2)O_(2))under mildly acidic conditions,while PAA-CaO_(2)nanoparticles exhibited good spray behavior in aqueous form.Tests demonstrated that PAA-CaO_(2)nanoparticles exhibited low cytotoxicity and allowed L929 cells proliferation and migration in vitro.The effectiveness of PAA-CaO_(2)nanoparticles in promoting wound healing and inhibiting bacterial growth in vivo was assessed in SD rats using full-thickness skin defect and Staphylococcus aureus(S.aureus)-infected wound models based thereon.The results revealed that PAA-CaO_(2)nanoparticles demonstrated significant advantages in both aspects.Notably,the infected rats’skin defects healed in 12 days.The benefits are linked to the functional role of Ca^(2+)coalesces with H_(2)O_(2)as known antibacterial and healing-promoted agents.Therefore,we developed nanoscale PAA-CaO_(2)sprays to prevent bacterial development and heal skin lesions.展开更多
Protein arginine methyltransferase 1(PRMT1),a type I PRMT,is overexpressed in gastric cancer(GC)cells.To elucidate the function of PRMT1 in GC,PRMT1 expression in HGC-27 and MKN-45 cells was knocked down by short hair...Protein arginine methyltransferase 1(PRMT1),a type I PRMT,is overexpressed in gastric cancer(GC)cells.To elucidate the function of PRMT1 in GC,PRMT1 expression in HGC-27 and MKN-45 cells was knocked down by short hairpin RNA(shRNA)or inhibited by PRMT1 inhibitors(AMI-1 or DCLX069),which resulted in inhibition of GC cell proliferation,migration,invasion,and tumorigenesis in vitro and in vivo.MLX-interacting protein(MLXIP)and Kinectin 1(KTN1)were identified as PRMT1-binding proteins.PRMT1 recruited MLXIP to the promoter ofβ-catenin,which inducedβ-catenin transcription and activated theβ-catenin signaling pathway,promoting GC cell migration and metastasis.Furthermore,KTN1 inhibited the K48-linked ubiquitination of PRMT1 by decreasing the interaction between TRIM48 and PRMT1.Collectively,our findings reveal a mechanism by which PRMT1 promotes cell proliferation and metastasis mediated by theβ-catenin signaling pathway.展开更多
Following the original article’s publication,[1]the authors declared that the affiliation of the first author Xiaoping Li was submitted incorrectly,while correct author affiliations should be as follows.The authors a...Following the original article’s publication,[1]the authors declared that the affiliation of the first author Xiaoping Li was submitted incorrectly,while correct author affiliations should be as follows.The authors apologize for any inconvenience caused.展开更多
Recently,Piper and Hoen et al.reported a new immunotherapy for pancreatic cancer in orthotopic pancreatic ductal adenocarcinoma(PDAC)KPC tumor model.1 They found that a murine PD-1-targeted IL-2 variant complex(PD1-IL...Recently,Piper and Hoen et al.reported a new immunotherapy for pancreatic cancer in orthotopic pancreatic ductal adenocarcinoma(PDAC)KPC tumor model.1 They found that a murine PD-1-targeted IL-2 variant complex(PD1-IL2v),in combination with radiation therapy(RT),can inhibit PDAC growth and metastasis by immune system,and induce a lasting immunological memory response to the tumor.展开更多
基金the National Key R&D Program of China(Grant Nos.2020YFA0509400 and 2019YFA0110300 to JC)the National Natural Science Foundation of China(Grant Nos.82150117 and 82071745 to JC and 31900570 to GJ)+2 种基金the Nanshan Scholarship of Guangzhou Medical University start-up fund(to GJ)the Science and Technology Program of Guangzhou(Grant No.202002030069 to JC)the Guangdong Project(Grant No.2019QN01Y212 to JC)。
文摘Macrophages are innate immune cells that are ubiquitously distributed throughout the vertebrate body.Macrophages orchestrate sophisticated processes in development,homeostasis,immunity,and disease1.Macrophages residing in tumor tissues are commonly known as tumor-associated macrophages(TAMs)and promote or inhibit tumor growth depending on the activation state2.
基金supported by the National Key R&D Program of China(Grant No.2022YFA1103300)the National Natural Science Foundation of China(Grant No.82020108004)+3 种基金the Natural Science Foundation of Chongqing Innovation Group Science Program(Grant No.cstc2021jcyjcxttX0001)the Natural Science Foundation of Chongqing(Grant No.CSTB2022NSCQ-MSX1060)the Special Project for Talent Construction in Xinqiao Hospital(Grant No.2022XKRC001)the National College Student Innovation and Entrepreneurship Training Program(Grant No.202190035001).
文摘Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host disease(GVHD)and complications of immunosuppressive drugs after allo-HSCT are the main causes of non-relapse mortality and a poor quality of life.In addition,GVHD and infusion-induced toxicity still occur with donor lymphocyte infusions(DLIs)and chimeric antigen receptor(CAR)T-cell therapy.Because of the special immune tolerance characteristics and anti-tumor ability of universal immune cells,universal immune cell therapy may strongly reduce GVHD,while simultaneously reducing tumor burden.Nevertheless,widespread application of universal immune cell therapy is mainly restricted by poor expansion and persistence efficacy.Many strategies have been applied to improve universal immune cell proliferation and persistence efficacy,including the use of universal cell lines,signaling regulation and CAR technology.In this review we have summarized current advances in universal immune cell therapy for hematologic malignancies with a discussion of future perspectives.
基金supported by grants from the National Natural Science Foundation of China(No.82020108004)the Hospital-level Clinical Innovation Military-Civilian Special Project of Army Medical University(No.2018JSLC0020)+1 种基金Chongqing Science and Technology Innovation Leading Talent(No.CSTCCXLJRC201718)Natural Science Foundation of Chongqing Innovation Group Science Program(No.cstc2021jcyj-cxttX0001).
文摘Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.
基金supported by the National Key Research and Development Program of China (Grant No.2023YFC3402100)the National Natural Science Foundation of China (Grant No.92259102)。
文摘Cancer stem cells(CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the existence of CSCs in various types of cancers and suggested that CSCs differentiate into diverse lineage cells that contribute to tumor progression. We may be able to overcome the limitations of cancer treatment with a comprehensive understanding of the biological features and mechanisms underlying therapeutic resistance in CSCs. This review provides an overview of the properties, biomarkers, and mechanisms of resistance shown by CSCs. Recent findings on metabolic features, especially fatty acid metabolism and ferroptosis in CSCs, are highlighted, along with promising targeting strategies. Targeting CSCs is a potential treatment plan to conquer cancer and prevent resistance and relapse in cancer treatment.
基金the National Natural Science Foundation of China(No.12032007,31971242 to G.Wang)the Science and Technology Innovation Project of Jinfeng Laboratory,Chongqing,China(No.jfkyjf202203001 to G.Wang).
文摘The clearance of apoptotic cell debris,containing professional phagocytosis and non-professional phagocytosis,is essential for maintaining the homeostasis of healthy tissues.Here,we discovered that endothelial cells could engulf apoptotic cell debris in atherosclerotic plaque.Single-cell RNA sequencing(RNA-seq)has revealed a unique endothelial cell subpopulation in atherosclerosis,which was strongly associated with vascular injury-related pathways.Moreover,integrated analysis of three vascular injury-related RNA-seq datasets showed that the expression of scavenger receptor class B type 1(SR-B1)was up-regulated and specifically enriched in the phagocytosis pathway under vascular injury circumstances.Single-cell RNA-seq and bulk RNA-seq indicate that SR-B1 was highly expressed in a unique endothelial cell subpopulation of mouse aorta and strongly associated with the reorganization of cellular adherent junctions and cytoskeleton which were necessary for phagocytosis.Furthermore,SR-B1 was strongly required for endothelial cells to engulf apoptotic cell debris in atherosclerotic plaque of both mouse and human aorta.Overall,this study demonstrated that apoptotic cell debris could be engulfed by endothelial cells through SR-B1 and associated with the reorganization of cellular adherent junctions and cytoskeleton.
基金the Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0330)the JinFeng Laboratory Foundation,Chongqing,China(jfkyjf202203001)+3 种基金the Project of Tutorial System of Medical Undergraduate in Lab Teaching and Management Center in Chongqing Medical University(LTMCMTS202109 and LTMCMTS202106)the Project of Scientific Research and Innovative Experiment for College Student in Chongqing Medical University(SRIEP202011,SRIEP202047,and SPIEP202167)the National Project of University Students Innovation and Entrepreneurship Training Program(S202010631016)Chongqing Municipal Education Commission Foundation(CYS22333).
文摘Although neuroelectrochemical sensing technology offers unique benefits for neuroscience research,its application is limited by substantial interference in complex brain environments while ensuring biosafety requirements.In this study,we introduced poly(3-hexylthiophene)(P3HT)and nitrogen-doped multiwalled carbon nanotubes(N-MWCNTs)to construct a composite membrane-modified carbon fiber microelectrode(CFME/P3HT-N-MWCNTs)for ascorbic acid(AA)detection.The microelectrode presented good linearity,selectivity,stability,antifouling,and biocompatibility and exhibited great performance for application in neuroelectrochemical sensing.Subsequently,we applied CFME/P3HT-N-MWCNTs to monitor AA release from in vitro nerve cells,ex vivo brain slices,and in vivo living rat brains and determined that glutamate can induce cell edema and AA release.We also found that glutamate activated the N-methyl-d-aspartic acid receptor,which enhanced Na^(+) and Cl^(−) inflow to induce osmotic stress,resulting in cytotoxic edema and ultimately AA release.This study is the first to observe the process of glutamate-induced brain cytotoxic edema with AA release and to reveal the mechanism.Our work can benefit the application of P3HT in in vivo implant microelectrode construction to monitor neurochemicals,understand the molecular basis of nervous system diseases,and discover certain biomarkers of brain diseases.
基金supported by grants from the National Natural Science Foundation of China(12032007,31971242,82270535)the Science and Technology Innovation Project of JinFeng Laboratory,Chongqing,China(jfkyjf202203001)。
文摘Objectives:To examine the 16-year developmental history,research hotspots,and emerging trends of zinc-based biodegradable metallic materials from the perspective of structural and temporal dynamics.Methods:The literature on zinc-based biodegradable metallic materials in WoSCC was searched.Historical characteristics,the evolution of active topics and development trends in the field of zinc-based biodegradable metallic materials were analyzed using the bibliometric tools CiteSpace and HistCite.Results:Over the past 16 years,the field of zinc-based biodegradable metal materials has remained in a hotspot stage,with extensive scientific collaboration.In addition,there are 45 subject categories and 51 keywords in different research periods,and 80 papers experience citation bursts.Keyword clustering anchored 3 emerging research subfields,namely,#1 plastic deformation#4 additive manufacturing#5 surface modification.The keyword alluvial map shows that the longest-lasting research concepts in the field are mechanical property,microstructure,corrosion behavior,etc.,and emerging keywords are additive manufacturing,surface modification,dynamic recrystallization,etc.The most recent research on reference clustering has six subfields.Namely,#0 microstructure,#2 sem,#3 additive manufacturing,#4 laser powder bed fusion,#5 implant,and#7 Zn-1Mg.Conclusion:The results of the bibliometric study provide the current status and trends of research on zinc-based biodegradable metallic materials,which can help researchers identify hot spots and explore new research directions in the field.
基金supported by the National Key R&D Program of China(Grant No.2021YFF1201004)the National Natural Science Foundation of China(Grant No.82273358,No.81802306,No.81903002,No.81672821,No.82071742,No.32270926)Natural Science Foundation of Guangdong Province of China(Grant No.2019A1515012196,No.2022A1515012059).
文摘Dysfunction of CD8^(+)T cells in the tumor microenvironment(TME)contributes to tumor immune escape and immunotherapy tolerance.The effects of hormones such as leptin,steroid hormones,and glucocorticoids on T cell function have been reported previously.However,the mechanism underlying thyroid-stimulating hormone(TSH)/thyroid-stimulating hormone receptor(TSHR)signaling in CD8^(+)T cell exhaustion and tumor immune evasion remain poorly understood.This study was aimed at investigating the effects of TSH/TSHR signaling on the function of CD8^(+)T cells and immune evasion in colorectal cancer(CRC).Methods:TSHR expression levels in CD8^(+)T cells were assessed with immunofluorescence and flow cytometry.Functional investigations involved manipulation of TSHR expression in cellular and mouse models to study its role in CD8^(+)T cells.Mechanistic insights were mainly gained through RNAsequencing,Western blotting,chromatin immunoprecipitation and luciferase activity assay.Immunofluorescence,flow cytometry and Western blotting were used to investigate the source of TSH and TSHR in CRC tissues.Results:TSHR was highly expressed in cancer cells and CD8^(+)T cells in CRC tissues.TSH/TSHR signaling was identified as the intrinsic pathway promoting CD8^(+)T cell exhaustion.Conditional deletion of TSHR in CD8^(+)tumorinfiltrating lymphocytes(TILs)improved effector differentiation and suppressed the expression of immune checkpoint receptors such as programmed cell death 1(PD-1)and hepatitis A virus cellular receptor 2(HAVCR2 or TIM3)through the protein kinase A(PKA)/cAMP-response element binding protein(CREB)signaling pathway.CRC cells secreted TSHR via exosomes to increase the TSHR level in CD8^(+)T cells,resulting in immunosuppression in the TME.Myeloid-derived suppressor cells(MDSCs)was the main source of TSH within the TME.Low expression of TSHR in CRC was a predictor of immunotherapy response.Conclusions:The present findings highlighted the role of endogenous TSH/TSHR signaling in CD8^(+)T cell exhaustion and immune evasion in CRC.TSHR may be suitable as a predictive and therapeutic biomarker in CRC immunotherapy.
基金supported by the National Natural Science Foundation of China(82330030,82271120,82121003,82201234)the CAMS Innovation Fund for Medical Sciences(2019-12 M-5-032,2021LY06)Sichuan Science and Technology Program(2021YFS0369,2022ZYD0131,24YSZH0012,23ZYZYTS0271,TB2023093,2023ZY0059)。
文摘High myopia(HM)is the primary cause of blindness,with the microstructural organization and composition of collagenous fibers in the cornea and sclera playing a crucial role in the biomechanical behavior of these tissues.In a previously reported myopic linkage region,MYP5(17q21-22),a potential candidate gene,LRRC46(c.C235T,p.Q79X),was identified in a large Han Chinese pedigree.LRRC46 is expressed in various eye tissues in humans and mice,including the retina,cornea,and sclera.In subsequent cell experiments,the mutation(c.C235T)decreased the expression of LRRC46 protein in human corneal epithelial cells(HCE-T).Further investigation revealed that Lrrc46^(-/-)mice(KO)exhibited a classical myopia phenotype.The thickness of the cornea and sclera in KO mice became thinner and more pronounced with age,the activity of limbal stem cells decreased,and microstructural changes were observed in the fibroblasts of the sclera and cornea.We performed RNA-seq on scleral and corneal tissues of KO and normal control wild-type(WT)mice,which indicated a significant downregulation of the collagen synthesis-related pathway(extracellular matrix,ECM)in KO mice.Subsequent in vitro studies further indicated that LRRC46,a member of the important LRR protein family,primarily affected the formation of collagens.This study suggested that LRRC46 is a novel candidate gene for HM,influencing collagen protein VⅢ(Col8a1)formation in the eye and gradually altering the biomechanical structure of the cornea and sclera,thereby promoting the occurrence and development of HM.
基金This work was supported by the pilot program of Southwest University(SWU-XDZD22006)the Natural Science Foundation of Chongqing(cstc2022ycjh-bgzxm0145)the Chongqing Postdoctoral Science Foundation(cstc2021jcyj-bsh0128).
文摘The proper transfer of genetic information from DNA to RNA to protein is essential for cell-fate control,development,and health.Methylation of DNA,RNAs,histones,and non-histone proteins is a reversible post-synthesis modification that finetunes gene expression and function in diverse physiological processes.Aberrant methylation caused by genetic mutations or environmental stimuli promotes various diseases and accelerates aging,necessitating the development of therapies to correct the disease-driver methylation imbalance.In this Review,we summarize the operating system of methylation across the central dogma,which includes writers,erasers,readers,and reader-independent outputs.We then discuss how dysregulation of the system contributes to neurological disorders,cancer,and aging.Current small-molecule compounds that target the modifiers show modest success in certain cancers.The methylome-wide action and lack of specificity lead to undesirable biological effects and cytotoxicity,limiting their therapeutic application,especially for diseases with a monogenic cause or different directions of methylation changes.Emerging tools capable of site-specific methylation manipulation hold great promise to solve this dilemma.With the refinement of delivery vehicles,these new tools are well positioned to advance the basic research and clinical translation of the methylation field.
基金supported by the National Key R&D Program of China(2022YFA1103300)the National Natural Science Foundation of China(81873424,81570097)+2 种基金the Natural Science Foundation of Chongqing Innovation Group Science Program(cstc2021jcyjcxttX0001)Clinical Medical Research Project of Army Medical University(2018XLC1006)and Translational Research Grant of NCRCH(2020ZKZC02).
文摘Background: Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown. Methods: Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca^(2+)-related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance. Results: Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca ^(2+ )is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments. Conclusions: Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.
基金This work was supported in part by grants from the National Natural Science Foundation of China(12032007,31971242)Chongqing Research Program of Basic research and Frontier Technology(cstc2019jcyj-zdxmX0028)+1 种基金JinFeng Laboratory Foundation,Chongqing,China(jfkyjf202203001)Shanghai Clinical Research Center for Interventional Medicine(19MC1910300).
文摘Purpose:This review aims to explore the history,research hotspots,and emerging trends of drug-eluting stents(DES)in the last two decades from the perspective of structural and temporal dynamics.Methods:Publications on DES were retrieved from WoSCC.The bibliometric tools including CiteSpace and HistCite were used to identify the historical features,the evolution of active topics,and emerging trends on the DES field.Results:In the last 20 years,the field of DES is still in the hot phase and there is a wide range of extensive scientific collaborations.In addition,active topics emerge in different periods,as evidenced by a total of 41 disciplines,511 keywords,and 1377 papers with citation bursts.Keyword clustering anchored five emerging research subfields,namely#0 dual antiplatelet therapy,#3 drug-coated balloon,#4 bifurcation,5#rotational atherectomy,and 6#quantitative flow ratio.The keyword alluvial map shows that the most persistent research concepts in this field are thrombosis,restenosis,etc.,and the emerging keywords are paclitaxel eluting balloon,coated balloon,drug-eluting balloon,etc.There are 7 recent research subfields anchored by reference clustering,namely#2 dual antiplatelet therapy,#4 drug-coated balloon,#5 peripheral artery disease,#8 fractional flow reserve,#10 bioresorbable vascular scaffold,#13 intravascular ultrasound,#14 biodegradable polymer.Conclusion:The findings based on the bibliometric studies provide the current status and trends in DES research and may help researchers to identify hot topics and explore new research directions in this field.
基金supported by the Natural Science Foundation of Chongqing(China)(No.cstc2019jcyj-zdxmX0033).
文摘LncMIR31HG acts as a host gene for miR-31,also known as LncHIFCAR(long non-coding HIF-1 co-activating RNA),whose deregulation has been reported to promote the development of various human cancers,including lung cancer,colorectal cancer,etc.1,2 However,the biological functions and molecular mechanisms of MIR31HG in gastric cancer are unclear.
基金This work was supported by grants from the Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0330,cstc2021jsyj-yzysbA0057,and cstc2019jcyj-zdxmX0028)the National Natural Science Foundation of China(31971242 and 12032007)+4 种基金the Project of Tutorial System of Medical Undergraduate in Lab Teaching&Management Center in Chongqing Medical University(LTMCMTS202005 and LTMCMTS202110)the JinFeng Laboratory Foundation of Chongqing(jfkyjf202203001)the Scientific and Technological Research Program of Chongqing Municipal Education Commission(KJQN202200426)the Scientific Research,the CQMU Program for Youth Innovation in Future Medicine(W0015)the Innovation Experimental Project of Chongqing Medical University(SRIEP202105).
文摘Multiple signal strategies remarkably improve the accuracy and efficiency of electrochemiluminescence(ECL)immunoassays,but the lack of potential-resolved luminophore pairs and chemical cross talk hinders their development.In this study,we synthesized a series of gold nanoparticles(AuNPs)/reduced graphene oxide(Au/rGO)composites as adjustable oxygen reduction reaction and oxygen evolution reaction catalysts to promote and modulate tris(2,2′-bipyridine)ruthenium(II)(Ru(bpy)_(3)^(2+))’s multisignal luminescence.With the increase in the diameter of AuNPs(3 to 30 nm),their ability to promote Ru(bpy)_(3)^(2+)’s anodic ECL was first impaired and then strengthened,and cathodic ECL was first enhanced and then weakened.Au/rGOs with medium-small and medium-large AuNP diameters remarkably increased Ru(bpy)_(3)^(2+)’s cathodic and anodic luminescence,respectively.Notably,the stimulation effects of Au/rGOs were superior to those of most existing Ru(bpy)_(3)^(2+)co-reactants.Moreover,we proposed a novel ratiometric immunosensor construction strategy using Ru(bpy)_(3)^(2+)’s luminescence promoter rather than luminophores as tags of antibodies to achieve signal resolution.This method avoids signal cross talk between luminophores and their respective co-reactants,which achieved a good linear range of 10−7 to 10−1 ng/ml and a limit of detection of 0.33 fg/ml for detecting carcinoembryonic antigen.This study addresses the previous scarcity of the macromolecular co-reactants of Ru(bpy)_(3)^(2+),broadening its application in biomaterial detection.Furthermore,the systematic clarification of the detailed mechanisms for converting the potential-resolved luminescence of Ru(bpy)_(3)^(2+)could facilitate an in-depth understanding of the ECL process and should inspire new designs of Ru(bpy)_(3)^(2+)luminescence enhancers or applications of Au/rGOs to other luminophores.This work removes some impediments to the development of multisignal ECL biodetection systems and provides vitality into their widespread applications.
基金supported by the National Natural Science Foundation of China(12032007,31971242)to G.W.the Chongqing Science and Technology Bureau(cstc2019jcyj-zdxmX0028)to G.W.JinFeng Laboratory,Chongqing,China(jfkyjf202203001)to G.W.
文摘Nanoparticles(NPs)hold tremendous targeting potential in cardiovascular disease and regenerative medicine,and exciting clinical applications are coming into light.Vascular endothelial cells(ECs)exposure to different magnitudes and patterns of shear stress(SS)generated by blood flow could engulf NPs in the blood.However,an unclear understanding of the role of SS on NP uptake is hindering the progress in improving the targeting of NP therapies.Here,the temporal and spatial distribution of SS in vascular ECs and the effect of different SS on NP uptake in ECs are highlighted.The mechanism of SS affecting NP uptake through regulating the cellular ROS level,endothelial glycocalyx and membrane fluidity is summarized,and the molecules containing clathrin and caveolin in the engulfment process are elucidated.SS targeting NPs are expected to overcome the current bottlenecks and change the field of targeting nanomedicine.This assessment on how SS affects the cell uptake of NPs and the marginalization of NPs in blood vessels could guide future research in cell biology and vascular targeting drugs.
基金supported by the National Natural Science Foundation of China(No.82020108004 and 81873424)the Natural Science Foundation of Chongqing,China(No.CSTB2022NSCQ-MSX1287)+2 种基金Special Funding for the Frontiers of Military Medical Basics(No.2018YQYLY002)Key Technical Innovation Projects in Clinical Fields of Xinqiao Hospital(No.2018JSLC0020)the Young Doctor Talent Incubation Program of Xinqiao Hospital(No.2022YQB016).
文摘Adoptive cell therapy(ACT)has emerged with remarkable efficacies for tumor immunotherapy.Chimeric antigen receptor(CAR)T cell therapy,as one of most promising ACTs,has achieved prominent effects in treating malignant hematological tumors.However,the insufficient killing activity and limited persistence of T cells in the immunosuppressive tumor microenvironment limit the further application of ACTs for cancer patients.Many studies have focused on improving cytotoxicity and persistence of T cells to achieve improved therapeutic effects.In this study,we explored the potential function in ACT of ginsenoside Rg1,the main pharmacologically active component of ginseng.We introduced Rg1 during the in vitro activation and expansion phase of T cells,and found that Rg1 treatment upregulated two T cell activation markers,CD69 and CD25,while promoting T cell differentiation towards a mature state.Transcriptome sequencing revealed that Rg1 influenced T cell metabolic reprogramming by strengthening mitochondrial biosynthesis.When co-cultured with tumor cells,Rg1-treated T cells showed stronger cytotoxicity than untreated cells.Moreover,adding Rg1 to the culture endowed CAR-T cells with enhanced anti-tumor efficacy.This study suggests that ginsenoside Rg1 provides a potential approach for improving the anti-tumor efficacy of ACT by enhancing T cell effector functions.
基金supported by grants from the Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0330,cstc2021jsyjyzysbA0057)the National Natural Science Foundation of China(31971242,12032007)+1 种基金the Science and Technology Innovation Project of Jinfeng Laboratory,Chongqing,China(jfkyjf202203001)the Project of Tutorial System of Medical Undergraduate in Lab Teaching&Management Center in Chongqing Medical University(LTMCMTS202107).
文摘The most common socioeconomic healthcare issues in clinical are burns,surgical incisions and other skin injuries.Skin lesion healing can be achieved with nanomedicines and other drug application techniques.This study developed a nano-spray based on cross-linked amorphous calcium peroxide(CaO_(2))nanoparticles of polyacrylic acid(PAA)for treating skin wounds(PAA-CaO_(2)nanoparticles).CaO_(2)serves as a‘drug’precursor,steadily and continuously releasing calcium ions(Ca^(2+))and hydrogen peroxide(H_(2)O_(2))under mildly acidic conditions,while PAA-CaO_(2)nanoparticles exhibited good spray behavior in aqueous form.Tests demonstrated that PAA-CaO_(2)nanoparticles exhibited low cytotoxicity and allowed L929 cells proliferation and migration in vitro.The effectiveness of PAA-CaO_(2)nanoparticles in promoting wound healing and inhibiting bacterial growth in vivo was assessed in SD rats using full-thickness skin defect and Staphylococcus aureus(S.aureus)-infected wound models based thereon.The results revealed that PAA-CaO_(2)nanoparticles demonstrated significant advantages in both aspects.Notably,the infected rats’skin defects healed in 12 days.The benefits are linked to the functional role of Ca^(2+)coalesces with H_(2)O_(2)as known antibacterial and healing-promoted agents.Therefore,we developed nanoscale PAA-CaO_(2)sprays to prevent bacterial development and heal skin lesions.
基金supported by the National Natural Science Foundation of China(No.82203339)the Postdoctoral Research Foundation of China(No.2021M692679)+1 种基金the Chongqing Postdoctoral Science Foundation(China)(No.7820100607)the Natural Science Foundation Project of Chongqing(China)(No.cstc2021jcyj-bsh0067 and cstc2022ycjh-bgzxm0145).
文摘Protein arginine methyltransferase 1(PRMT1),a type I PRMT,is overexpressed in gastric cancer(GC)cells.To elucidate the function of PRMT1 in GC,PRMT1 expression in HGC-27 and MKN-45 cells was knocked down by short hairpin RNA(shRNA)or inhibited by PRMT1 inhibitors(AMI-1 or DCLX069),which resulted in inhibition of GC cell proliferation,migration,invasion,and tumorigenesis in vitro and in vivo.MLX-interacting protein(MLXIP)and Kinectin 1(KTN1)were identified as PRMT1-binding proteins.PRMT1 recruited MLXIP to the promoter ofβ-catenin,which inducedβ-catenin transcription and activated theβ-catenin signaling pathway,promoting GC cell migration and metastasis.Furthermore,KTN1 inhibited the K48-linked ubiquitination of PRMT1 by decreasing the interaction between TRIM48 and PRMT1.Collectively,our findings reveal a mechanism by which PRMT1 promotes cell proliferation and metastasis mediated by theβ-catenin signaling pathway.
文摘Following the original article’s publication,[1]the authors declared that the affiliation of the first author Xiaoping Li was submitted incorrectly,while correct author affiliations should be as follows.The authors apologize for any inconvenience caused.
基金the National Natural Science Foundation of China(81872028,to H.M.)Chongqing Fund for Outstanding Youth(CSTB2022NSCQ-JQX0010 to H.M.).
文摘Recently,Piper and Hoen et al.reported a new immunotherapy for pancreatic cancer in orthotopic pancreatic ductal adenocarcinoma(PDAC)KPC tumor model.1 They found that a murine PD-1-targeted IL-2 variant complex(PD1-IL2v),in combination with radiation therapy(RT),can inhibit PDAC growth and metastasis by immune system,and induce a lasting immunological memory response to the tumor.
