Given that the concurrent L1-minimization(L1-min)problem is often required in some real applications,we investigate how to solve it in parallel on GPUs in this paper.First,we propose a novel self-adaptive warp impleme...Given that the concurrent L1-minimization(L1-min)problem is often required in some real applications,we investigate how to solve it in parallel on GPUs in this paper.First,we propose a novel self-adaptive warp implementation of the matrix-vector multiplication(Ax)and a novel self-adaptive thread implementation of the matrix-vector multiplication(ATx),respectively,on the GPU.The vector-operation and inner-product decision trees are adopted to choose the optimal vector-operation and inner-product kernels for vectors of any size.Second,based on the above proposed kernels,the iterative shrinkage-thresholding algorithm is utilized to present two concurrent L1-min solvers from the perspective of the streams and the thread blocks on a GPU,and optimize their performance by using the new features of GPU such as the shuffle instruction and the read-only data cache.Finally,we design a concurrent L1-min solver on multiple GPUs.The experimental results have validated the high effectiveness and good performance of our proposed methods.展开更多
Compressive sensing(CS)is an emerging methodology in computational signal processing that has recently attracted intensive research activities.At present,the basic CS theory includes recoverability and stability:the f...Compressive sensing(CS)is an emerging methodology in computational signal processing that has recently attracted intensive research activities.At present,the basic CS theory includes recoverability and stability:the former quantifies the central fact that a sparse signal of length n can be exactly recovered from far fewer than n measurements via l1-minimization or other recovery techniques,while the latter specifies the stability of a recovery technique in the presence of measurement errors and inexact sparsity.So far,most analyses in CS rely heavily on the Restricted Isometry Property(RIP)for matrices.In this paper,we present an alternative,non-RIP analysis for CS via l1-minimization.Our purpose is three-fold:(a)to introduce an elementary and RIP-free treatment of the basic CS theory;(b)to extend the current recoverability and stability results so that prior knowledge can be utilized to enhance recovery via l1-minimization;and(c)to substantiate a property called uniform recoverability of l1-minimization;that is,for almost all random measurement matrices recoverability is asymptotically identical.With the aid of two classic results,the non-RIP approach enables us to quickly derive from scratch all basic results for the extended theory.展开更多
Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
Objective:Lung cancer is the most common cause of cancer-related deaths worldwide.Platinum-based chemotherapy is one of the main treatment options for patients with non-small cell lung cancer(NSCLC)but the effectivene...Objective:Lung cancer is the most common cause of cancer-related deaths worldwide.Platinum-based chemotherapy is one of the main treatment options for patients with non-small cell lung cancer(NSCLC)but the effectiveness of chemotherapy is encumbered by drug resistance.Therefore,understanding the molecular mechanisms underlying chemotherapy resistance is crucial in improving treatment outcomes and prognosis.Methods:The cell viability assay and apoptosis were used to analyze chemoresistance.Western blot analysis and wound healing testing were used to evaluate the epithelial-to-mesenchymal transition(EMT).Immunoprecipitation was used for analysis of protein modification.Promoter activity was determined using the luciferase reporter assay.Immunofluorescence staining was used to determine reactive oxygen species levels.The expression patterns of EMT markers and carnitine palmitoyltransferase 1C(CPT1C)were determined by Western blot analysis.Results:CPT1C,which was shown to be highly expressed in lung cancer,is associated with cisplatin resistance in NSCLC cells.CPT1C depletion increased NSCLC cell sensitivity to cisplatin,while overexpression of CPT1C increased NSCLC cell resistance to cisplatin.Induction of EMT mediated CPT1C-induced cisplatin resistance.Ectopic expression of Snail reversed the increase in cisplatin sensitivity triggered by CPT1C knockdown.Moreover,CPT1C was shown to be regulated at the post-translational level and an E3-ubiquitin ligase,NEDD4L,was shown to be a major regulator of CPT1C stability and activity.Conclusions:These data provide evidence for the first time that the lipid metabolism enzyme,CPT1C,mediates resistance to chemotherapy.Therefore,the use of combination therapy with a CPT1C inhibitor may be a promising new avenue in lung cancer treatment.展开更多
基金The research has been supported by the Natural Science Foundation of China under great number 61872422the Natural Science Foundation of Zhejiang Province,China under great number LY19F020028.
文摘Given that the concurrent L1-minimization(L1-min)problem is often required in some real applications,we investigate how to solve it in parallel on GPUs in this paper.First,we propose a novel self-adaptive warp implementation of the matrix-vector multiplication(Ax)and a novel self-adaptive thread implementation of the matrix-vector multiplication(ATx),respectively,on the GPU.The vector-operation and inner-product decision trees are adopted to choose the optimal vector-operation and inner-product kernels for vectors of any size.Second,based on the above proposed kernels,the iterative shrinkage-thresholding algorithm is utilized to present two concurrent L1-min solvers from the perspective of the streams and the thread blocks on a GPU,and optimize their performance by using the new features of GPU such as the shuffle instruction and the read-only data cache.Finally,we design a concurrent L1-min solver on multiple GPUs.The experimental results have validated the high effectiveness and good performance of our proposed methods.
文摘Compressive sensing(CS)is an emerging methodology in computational signal processing that has recently attracted intensive research activities.At present,the basic CS theory includes recoverability and stability:the former quantifies the central fact that a sparse signal of length n can be exactly recovered from far fewer than n measurements via l1-minimization or other recovery techniques,while the latter specifies the stability of a recovery technique in the presence of measurement errors and inexact sparsity.So far,most analyses in CS rely heavily on the Restricted Isometry Property(RIP)for matrices.In this paper,we present an alternative,non-RIP analysis for CS via l1-minimization.Our purpose is three-fold:(a)to introduce an elementary and RIP-free treatment of the basic CS theory;(b)to extend the current recoverability and stability results so that prior knowledge can be utilized to enhance recovery via l1-minimization;and(c)to substantiate a property called uniform recoverability of l1-minimization;that is,for almost all random measurement matrices recoverability is asymptotically identical.With the aid of two classic results,the non-RIP approach enables us to quickly derive from scratch all basic results for the extended theory.
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
基金Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBJC00001the Key Discipline Special Project of Tianjin Municipal Health Commission,No.TJWJ2022XK016.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.
基金supported by the National Natural Science Foundation of China(Grant No.81872371)the Open Project Program of State Key Laboratory of Molecular Oncology(Grant No.SKL-KF-2019-11)+3 种基金the Program for Excellent Sci-tech Innovation Teams of Universities in Anhui Province(Grant No.2023AH010073)the Provincial-level Quality Project in Higher Education Institutions of Anhui Province(Grant No.2022jyxm1710)the College Students Innovation and Entrepreneurship Training Program(Grant No.S202310368028 and S202410368035)the Health Science Research Project of Anhui Province(Grant No.AHWJ2022a028)。
文摘Objective:Lung cancer is the most common cause of cancer-related deaths worldwide.Platinum-based chemotherapy is one of the main treatment options for patients with non-small cell lung cancer(NSCLC)but the effectiveness of chemotherapy is encumbered by drug resistance.Therefore,understanding the molecular mechanisms underlying chemotherapy resistance is crucial in improving treatment outcomes and prognosis.Methods:The cell viability assay and apoptosis were used to analyze chemoresistance.Western blot analysis and wound healing testing were used to evaluate the epithelial-to-mesenchymal transition(EMT).Immunoprecipitation was used for analysis of protein modification.Promoter activity was determined using the luciferase reporter assay.Immunofluorescence staining was used to determine reactive oxygen species levels.The expression patterns of EMT markers and carnitine palmitoyltransferase 1C(CPT1C)were determined by Western blot analysis.Results:CPT1C,which was shown to be highly expressed in lung cancer,is associated with cisplatin resistance in NSCLC cells.CPT1C depletion increased NSCLC cell sensitivity to cisplatin,while overexpression of CPT1C increased NSCLC cell resistance to cisplatin.Induction of EMT mediated CPT1C-induced cisplatin resistance.Ectopic expression of Snail reversed the increase in cisplatin sensitivity triggered by CPT1C knockdown.Moreover,CPT1C was shown to be regulated at the post-translational level and an E3-ubiquitin ligase,NEDD4L,was shown to be a major regulator of CPT1C stability and activity.Conclusions:These data provide evidence for the first time that the lipid metabolism enzyme,CPT1C,mediates resistance to chemotherapy.Therefore,the use of combination therapy with a CPT1C inhibitor may be a promising new avenue in lung cancer treatment.
