Objectives Chronic lymphocytic leukemia(CLL)is characterized by progressive immune dysregulation.Invariant natural killer T(iNKT)cells support immune surveillance,but the clinical relevance of their regulatory subsets...Objectives Chronic lymphocytic leukemia(CLL)is characterized by progressive immune dysregulation.Invariant natural killer T(iNKT)cells support immune surveillance,but the clinical relevance of their regulatory subsets remains unclear.FoxP3+regulatory iNKT cells(iNKTreg)and E4BP4+IL-10+(iNKT10)cells may reflect immunoregulatory changes associated with disease progression.The study aimed to quantify circulating iNKTreg and iNKT10 subsets and monocytic myeloid-derived suppressor cells(M-MDSCs)in treatment-naïve CLL patients and evaluate their associations with disease characteristics and time to first treatment(TTFT).Methods Peripheral blood samples from 60 untreated CLL patients and 20 healthy donors were analyzed by flow cytometry to determine iNKTreg and iNKT10 percentages,as well as indoleamine 2,3-dioxygenase(IDO)-expressing M-MDSCs.Receiver operating characteristic(ROC)curves and Cox proportional hazards models were used to assess prognostic significance.Results iNKTreg and iNKT10 percentages were significantly increased in CLL compared with healthy donors(p=0.002).Elevated iNKTreg frequencies were associated with zeta-chain-associated protein of 70 kD(ZAP-70)positivity(p=0.017),CD38 positivity(p=0.048),and treatment requirement during follow-up(p=0.016).Based on an ROC-derived cut-off of 9.6%(AUC=0.753),patients with iNKTreg≥9.6%had shorter TTFT(hazard ratio[HR]=2.71;95%confidence interval[CI],1.13–6.49;p=0.025),although the association was not retained in multivariate analysis(HR=1.27;95%CI,0.44–3.64;p=0.626).iNKTreg and iNKT10 percentages correlated positively with IDO+M-MDSCs(p=0.035 and p=0.044),but not with arginase-1(ARG1)or inducible nitric oxide synthase(NOS2).Conclusion Elevated iNKTreg levels reflect a more aggressive disease phenotype and associate with shorter TTFT in univariate analysis,supporting their exploration as complementary immunological biomarkers in CLL.Functional studies and validation in larger cohorts are needed to determine their prognostic and biological significance.展开更多
In the references[4,11,12],the authors gave some modular forms overΓ^(0)(2).In this note,we proceed with the study of cancellation formulas relating to the modular forms.
Gamma delta(γδ)T cells and invariant natural killer T(iNKT)cells are unconventional T cells with limited T cell receptor(TCR)diversity.Both can recognize lipid or non-peptide antigens,often through cluster of differ...Gamma delta(γδ)T cells and invariant natural killer T(iNKT)cells are unconventional T cells with limited T cell receptor(TCR)diversity.Both can recognize lipid or non-peptide antigens,often through cluster of differentiation 1d(CD1d),rapidly produce cytokines,express natural killer(NK)cell markers,and are mainly found in mucosal and barrier tissues.Acting as a bridge between innate and adaptive immunity,they show great promise for cancer immunotherapy.DevelopingγδT and iNKT cells for treatment involves shared features like thymic origin,MHC-independent recognition,rapid cytotoxicity,low graft-vs.-host disease(GvHD)risk,ex vivo expansion,and genetic modification,making them suitable for adoptive cell therapies.While their mechanisms are similar,iNKT cells rely on CD1d-mediated antigen presentation,provided by CD1d-expressing antigen-presenting cells(APCs)or engineered cell lines,to activate their invariant TCR and expand effectively.Chimeric antigen receptors(CAR)-induced functional activations make these cell types viable alternatives to conventional cell-based or CAR-T therapies with additional safety benefits.Early clinical trials have shown encouraging results,and their completion will confirm their potential for future treatments.This review explores the biology and mechanisms ofγδT and iNKT cells,focusing on how APCs,cytokines,feeder cells,and CARs contribute to boosting their cytotoxic function,cytokine production,and expansion,enhancing their promise as cancer immunotherapies.It also explores the advancements and challenges in developingγδT and iNKT cell-based immunotherapies,with preclinical and early clinical outcomes offering promising insights.展开更多
在基于机器视觉的智能检测领域,工件外轮廓缺陷检测需要自动提取图像中的感兴趣区域(Regions of Interest,ROI),利用Canny边缘检测算子进一步获取工件的外轮廓。为此,采用Hu不变矩计算工件最外层轮廓,并利用该方法进行缺陷检测。首先,...在基于机器视觉的智能检测领域,工件外轮廓缺陷检测需要自动提取图像中的感兴趣区域(Regions of Interest,ROI),利用Canny边缘检测算子进一步获取工件的外轮廓。为此,采用Hu不变矩计算工件最外层轮廓,并利用该方法进行缺陷检测。首先,对采集到的工件图像进行灰度化、去噪和反转二值图像等预处理。其次,计算图像外轮廓的Hu不变矩及其相似度系数。通过将计算得到的图像相似度系数与设定阈值进行比较,实现工件的缺陷检测。实验结果表明,该方法在缺陷检测方面的准确率超过90%,匹配时间保持在1000 ms以内,同时满足设计要求中的可靠性、稳定性、实时性及高检测精度。展开更多
基金funded by the Medical University of Lublin,Poland,grant number DS 458.
文摘Objectives Chronic lymphocytic leukemia(CLL)is characterized by progressive immune dysregulation.Invariant natural killer T(iNKT)cells support immune surveillance,but the clinical relevance of their regulatory subsets remains unclear.FoxP3+regulatory iNKT cells(iNKTreg)and E4BP4+IL-10+(iNKT10)cells may reflect immunoregulatory changes associated with disease progression.The study aimed to quantify circulating iNKTreg and iNKT10 subsets and monocytic myeloid-derived suppressor cells(M-MDSCs)in treatment-naïve CLL patients and evaluate their associations with disease characteristics and time to first treatment(TTFT).Methods Peripheral blood samples from 60 untreated CLL patients and 20 healthy donors were analyzed by flow cytometry to determine iNKTreg and iNKT10 percentages,as well as indoleamine 2,3-dioxygenase(IDO)-expressing M-MDSCs.Receiver operating characteristic(ROC)curves and Cox proportional hazards models were used to assess prognostic significance.Results iNKTreg and iNKT10 percentages were significantly increased in CLL compared with healthy donors(p=0.002).Elevated iNKTreg frequencies were associated with zeta-chain-associated protein of 70 kD(ZAP-70)positivity(p=0.017),CD38 positivity(p=0.048),and treatment requirement during follow-up(p=0.016).Based on an ROC-derived cut-off of 9.6%(AUC=0.753),patients with iNKTreg≥9.6%had shorter TTFT(hazard ratio[HR]=2.71;95%confidence interval[CI],1.13–6.49;p=0.025),although the association was not retained in multivariate analysis(HR=1.27;95%CI,0.44–3.64;p=0.626).iNKTreg and iNKT10 percentages correlated positively with IDO+M-MDSCs(p=0.035 and p=0.044),but not with arginase-1(ARG1)or inducible nitric oxide synthase(NOS2).Conclusion Elevated iNKTreg levels reflect a more aggressive disease phenotype and associate with shorter TTFT in univariate analysis,supporting their exploration as complementary immunological biomarkers in CLL.Functional studies and validation in larger cohorts are needed to determine their prognostic and biological significance.
文摘In the references[4,11,12],the authors gave some modular forms overΓ^(0)(2).In this note,we proceed with the study of cancellation formulas relating to the modular forms.
文摘Gamma delta(γδ)T cells and invariant natural killer T(iNKT)cells are unconventional T cells with limited T cell receptor(TCR)diversity.Both can recognize lipid or non-peptide antigens,often through cluster of differentiation 1d(CD1d),rapidly produce cytokines,express natural killer(NK)cell markers,and are mainly found in mucosal and barrier tissues.Acting as a bridge between innate and adaptive immunity,they show great promise for cancer immunotherapy.DevelopingγδT and iNKT cells for treatment involves shared features like thymic origin,MHC-independent recognition,rapid cytotoxicity,low graft-vs.-host disease(GvHD)risk,ex vivo expansion,and genetic modification,making them suitable for adoptive cell therapies.While their mechanisms are similar,iNKT cells rely on CD1d-mediated antigen presentation,provided by CD1d-expressing antigen-presenting cells(APCs)or engineered cell lines,to activate their invariant TCR and expand effectively.Chimeric antigen receptors(CAR)-induced functional activations make these cell types viable alternatives to conventional cell-based or CAR-T therapies with additional safety benefits.Early clinical trials have shown encouraging results,and their completion will confirm their potential for future treatments.This review explores the biology and mechanisms ofγδT and iNKT cells,focusing on how APCs,cytokines,feeder cells,and CARs contribute to boosting their cytotoxic function,cytokine production,and expansion,enhancing their promise as cancer immunotherapies.It also explores the advancements and challenges in developingγδT and iNKT cell-based immunotherapies,with preclinical and early clinical outcomes offering promising insights.
文摘在基于机器视觉的智能检测领域,工件外轮廓缺陷检测需要自动提取图像中的感兴趣区域(Regions of Interest,ROI),利用Canny边缘检测算子进一步获取工件的外轮廓。为此,采用Hu不变矩计算工件最外层轮廓,并利用该方法进行缺陷检测。首先,对采集到的工件图像进行灰度化、去噪和反转二值图像等预处理。其次,计算图像外轮廓的Hu不变矩及其相似度系数。通过将计算得到的图像相似度系数与设定阈值进行比较,实现工件的缺陷检测。实验结果表明,该方法在缺陷检测方面的准确率超过90%,匹配时间保持在1000 ms以内,同时满足设计要求中的可靠性、稳定性、实时性及高检测精度。
