Circulating tumor cells(CTCs)are precursors of distant metastasis in a subset of cancer patients.A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the ...Circulating tumor cells(CTCs)are precursors of distant metastasis in a subset of cancer patients.A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis.It remains elusive how CTCs evade immune surveillance and elimination by immune cells.In this study,we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle(EVs)-derived CD45(termed as CD45^(+)CTCs)that resisted T cell attack.A higher percentage of CD45^(+)CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients.Moreover,CD45^(+)tumor cells orchestrated an immunosuppressive milieu and CD45^(+)CTCs exhibited remarkably stronger metastatic potential than CD45−CTCs in vivo.Mechanistically,CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells,thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response.Together,these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis,providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.展开更多
Objective Traditional Chinese medicine exhibits positive therapeutic effects as a primary or adjunctive treatment for diabetic nephropathy(DN).This study aimed to evaluate the impact and mechanism of action of Xiaoke ...Objective Traditional Chinese medicine exhibits positive therapeutic effects as a primary or adjunctive treatment for diabetic nephropathy(DN).This study aimed to evaluate the impact and mechanism of action of Xiaoke decoction(XKD),a traditional Chinese medicine,on renal function in DN rats.Methods A rat model of DN was established,and the rats were divided into five groups(n=7 per group):normal control group(NC),DN model group(DN),low-dose XKD treatment group(DN+XKD-L,1.5 g/kg/d),high-dose XKD treatment group(DN+XKD-H,6 g/kg/d),and cyclooxygenase-2(COX-2)inhibitor(NS398)treatment group(DN+NS398,8 mg/kg/d).Medications were administered via gavage for 12 consecutive weeks,while equal volumes of normal saline were given to the NC and DN groups.A glucometer was used to detect changes in blood glucose(BG).Enzyme-linked immunosorbent assay(ELISA)and an automatic biochemical analyzer were employed to measure levels of insulin,serum creatinine(Scr),blood urea nitrogen(BUN),triglyceride(TG),total cholesterol(TC),high-density lipoprotein(HDL),low-density lipoprotein(LDL),and 24-h urine protein quantity(UP/24 h)in rats.Renal tissue sections from different treatment groups were prepared,with tissue lesions examined via periodic acid-Schiff(PAS)and hematoxylin–eosin(HE)staining.Tissue inflammation and lipid deposition were evaluated using ELISA and Oil Red O staining.Immunohistochemistry and Western blotting were used to detect changes in the expression levels of COX-2 and low-density lipoprotein receptor(LDLr)in tissues,and to clarify the regulatory mechanism of XKD on renal function in DN rats.Results XKD,particularly at the high dose(XKD-H,6 g/kg/d),significantly reduced BG,insulin levels,renal weight ratio,Scr,BUN,and UP/24 h in DN rats.DN rats showed significant renal lesions,and XKD gavage(especially XKD-H)markedly improved these pathological changes.In DN rats,XKD significantly decreased the protein expression levels of COX-2 and LDLr,downregulated the levels of inflammatory factors and lipid factors,reduced lipid deposition in renal tissues,and ameliorated structural abnormalities in glomeruli,basement membranes,and renal tubules.Conclusions XKD alleviates renal tissue damage by regulating the COX-2-mediated LDLr pathway,thereby reducing the release of inflammatory factors and lipid accumulation in DN rats and protecting renal function.Graphical Abstract XKD improves renal function in streptozotocin(STZ)-induced DN rats by regulating the COX-2-mediated LDLr pathway,reducing inflammatory factors and lipid deposition,and alleviating renal tissue damage.展开更多
Spin relaxation induced by the interfacial effects in GaN/Al_(0.25) Ga_(0.75) N heterostructures was carefully investigated using a photon-energy-dependent time-resolved Kerr rotation spectrum.The existence of the int...Spin relaxation induced by the interfacial effects in GaN/Al_(0.25) Ga_(0.75) N heterostructures was carefully investigated using a photon-energy-dependent time-resolved Kerr rotation spectrum.The existence of the interfacial localized states with potential fluctuations at the GaN/AlGaN heterointerface leads to photoluminescence peaks showing blue and S-shaped shifts owing to the excitation power and temperature,respectively.Photoexcited electrons in the localized states show a spin relaxation time longer than 1 ns because of the suppression of the D’yakonov-Perel’(DP)scattering,while the spin relaxation time of free electrons was approximately only 10 ps because of the giant Rashba spin-orbit coupling induced by the interfacial polarization field under the framework of the DP scattering mechanism.Furthermore,it is found that the high electron mobility at the heterointerface results in a long spin diffusion length of 300 nm at high temperatures,which is promising for the development of GaN-based spintronic devices.展开更多
基金supported by the National Natural Science Foundation of China(No:U21A20421,82073882,82203649)the Key Project of Science Technology Program of Guangzhou(No:2023B03J0029)National Key R&D Program of China(No:2022YFE0209700).
文摘Circulating tumor cells(CTCs)are precursors of distant metastasis in a subset of cancer patients.A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis.It remains elusive how CTCs evade immune surveillance and elimination by immune cells.In this study,we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle(EVs)-derived CD45(termed as CD45^(+)CTCs)that resisted T cell attack.A higher percentage of CD45^(+)CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients.Moreover,CD45^(+)tumor cells orchestrated an immunosuppressive milieu and CD45^(+)CTCs exhibited remarkably stronger metastatic potential than CD45−CTCs in vivo.Mechanistically,CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells,thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response.Together,these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis,providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.
基金supported by the Budget Project of Shanghai University of Traditional Chinese Medicine(18LK058).
文摘Objective Traditional Chinese medicine exhibits positive therapeutic effects as a primary or adjunctive treatment for diabetic nephropathy(DN).This study aimed to evaluate the impact and mechanism of action of Xiaoke decoction(XKD),a traditional Chinese medicine,on renal function in DN rats.Methods A rat model of DN was established,and the rats were divided into five groups(n=7 per group):normal control group(NC),DN model group(DN),low-dose XKD treatment group(DN+XKD-L,1.5 g/kg/d),high-dose XKD treatment group(DN+XKD-H,6 g/kg/d),and cyclooxygenase-2(COX-2)inhibitor(NS398)treatment group(DN+NS398,8 mg/kg/d).Medications were administered via gavage for 12 consecutive weeks,while equal volumes of normal saline were given to the NC and DN groups.A glucometer was used to detect changes in blood glucose(BG).Enzyme-linked immunosorbent assay(ELISA)and an automatic biochemical analyzer were employed to measure levels of insulin,serum creatinine(Scr),blood urea nitrogen(BUN),triglyceride(TG),total cholesterol(TC),high-density lipoprotein(HDL),low-density lipoprotein(LDL),and 24-h urine protein quantity(UP/24 h)in rats.Renal tissue sections from different treatment groups were prepared,with tissue lesions examined via periodic acid-Schiff(PAS)and hematoxylin–eosin(HE)staining.Tissue inflammation and lipid deposition were evaluated using ELISA and Oil Red O staining.Immunohistochemistry and Western blotting were used to detect changes in the expression levels of COX-2 and low-density lipoprotein receptor(LDLr)in tissues,and to clarify the regulatory mechanism of XKD on renal function in DN rats.Results XKD,particularly at the high dose(XKD-H,6 g/kg/d),significantly reduced BG,insulin levels,renal weight ratio,Scr,BUN,and UP/24 h in DN rats.DN rats showed significant renal lesions,and XKD gavage(especially XKD-H)markedly improved these pathological changes.In DN rats,XKD significantly decreased the protein expression levels of COX-2 and LDLr,downregulated the levels of inflammatory factors and lipid factors,reduced lipid deposition in renal tissues,and ameliorated structural abnormalities in glomeruli,basement membranes,and renal tubules.Conclusions XKD alleviates renal tissue damage by regulating the COX-2-mediated LDLr pathway,thereby reducing the release of inflammatory factors and lipid accumulation in DN rats and protecting renal function.Graphical Abstract XKD improves renal function in streptozotocin(STZ)-induced DN rats by regulating the COX-2-mediated LDLr pathway,reducing inflammatory factors and lipid deposition,and alleviating renal tissue damage.
基金supported by the National Key Research and Development Program of China(Grants No.2018YFB0406603 and 2018YFE0125700)the National Natural Science Foundation of China(Grants No.61574006,61522401,61927806,61521004,and 11634002).
文摘Spin relaxation induced by the interfacial effects in GaN/Al_(0.25) Ga_(0.75) N heterostructures was carefully investigated using a photon-energy-dependent time-resolved Kerr rotation spectrum.The existence of the interfacial localized states with potential fluctuations at the GaN/AlGaN heterointerface leads to photoluminescence peaks showing blue and S-shaped shifts owing to the excitation power and temperature,respectively.Photoexcited electrons in the localized states show a spin relaxation time longer than 1 ns because of the suppression of the D’yakonov-Perel’(DP)scattering,while the spin relaxation time of free electrons was approximately only 10 ps because of the giant Rashba spin-orbit coupling induced by the interfacial polarization field under the framework of the DP scattering mechanism.Furthermore,it is found that the high electron mobility at the heterointerface results in a long spin diffusion length of 300 nm at high temperatures,which is promising for the development of GaN-based spintronic devices.
