Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord...Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.展开更多
AIM To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis. METHODS A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3'-UTR. MiR...AIM To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis. METHODS A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3'-UTR. MiR-155 mimics, negative controls and SHIP-1 expression/knockdown vectors were established and then utilized in gain-and loss-of-function studies performed in raw264.7 cells and primary bone marrow-derived macrophages (BMDMs). Thereafter, dextran sulfate sodium (DSS)-induced colitis mouse model with or without antagomiR-155 treatment was established, and the levels of miR-155 and SHIP-1, as well as the pro-inflammatory capabilities, were measured by western blot, quantitative polymerase chain reaction, and immunohistochemistry. RESULTS MiR-155 directly bound to the 3'-UTR of SHIP-1 mRNA and induced a significant decrease in SHIP-1 expression in both raw264.7 cells and primary BMDMs. MiR-155 markedly promoted cell proliferation and proinflammatory secretions including IL-6, TNF-alpha, IL-1 beta, and IFN-gamma, whereas these effects could be reversed by the restoration of SHIP-1 expression. In vivo studies showed that antagomiR-155 administration could alleviate DSS-induced intestinal inflammation in Balb/c mice. Moreover, significantly increased SHIP-1 expression, as well as decreased Akt activation and in-flammatory response, were observed in the antagomiR-155-treated mice. CONCLUSION MiR-155 promotes experimental colitis by repressing SHIP-1 expression. Thus, the inhibition of miR-155 might be a promising strategy for therapy.展开更多
AIM: To investigate the effect of Lianshu preparation on lipopolysaccharide (LPS)-induced diarrhea in rats. METHODS: A diarrhea model was established in Sprague Dawley rats via injection of 1 mL of 30 mg/kg LPS. A...AIM: To investigate the effect of Lianshu preparation on lipopolysaccharide (LPS)-induced diarrhea in rats. METHODS: A diarrhea model was established in Sprague Dawley rats via injection of 1 mL of 30 mg/kg LPS. A total of 40 rats were randomly divided into normal group, LPS group, LPS + Lianshu group, LPS + berberine group (n = 10 in each group). Their intestinal mucosal barrier and frequency of diarrhea were observed. Levels of glucose, serum Na^+, K^+, Cl and hematocrit, plasma nitrogen monoxide (NO), diamine oxidase (DAO), and D (-)-lactate were measured. The number of IgA+ plasma cells in small intestine was detected and SIgA levels in the intestinal fluid were measured. The antipyretic activity of Lianshu preparation in rats was evaluated using Brewer's yeast-induced pyrexia (10 mL/kg of 20% aqueous suspension). Acetaminophen (250 mg/kg, intragastric administration, bid) was comparison. Temperature used as a standard drug for was recorded 1 h before and 6 h after Brewer's yeast injection. Finally, small intestina transmission in mice treated with Lianshu was detected after intraperitoneal injection of methyl prostigmin (2 mg/kg). Atropine (10 g/kg) was used as a control. The ink content in intestine was determined and the total length of intestine was measured. RESULTS: The frequency of diarrhea was higher in LPS group than in LPS + Lianshu group and LPS + berberine group (36.70± 5.23 vs 28.50 ±4.06 and 32.70±9.30 respectively, P 〈 0.01), and lower in LP5 + Lianshu group than in LPS + berberine group (P = 0.03). The levels of Na+, glucose, Cl, K^+ were significantly lower in LPS + Lianshu group than in LPS + berberine group (140.35±3.19 mmol/L vs 131.99±4.86 mmol/L, 8.49 ±1.84 mmol/L vs 6.54±2.30 mmol/L, 106.29± 4.41 mmol/L vs 102.5±1.39 mmol/L, 5.08±0.66 mmol/L vs 4.32 ± 0.62 mmol/L respectively, P 〈 0.05). The level of hematocrit was lower in LPS + Lianshu group than in LPS + berberine group (0.50% ±0.07% vs 0.59%± 0.10% respectively, P 〈 0.05). The plasma levels of NO, DAO and D (-)-lactate were higher in LPS group than in normal group (79.74 ± 7.39μmol/L vs 24.94 ± 3.38μmol/L, 2.48 ±0.42μ/mL vs 0.82 ±0.33 p/mL, 5.63± 0.85μg/mL vs 2.01 ±0.32 μg/mL respectively, P 〈 0.01), and lower in LPS + Lianshu group than in LP5 + berberine group (48.59±4.70μmol/L vs 51.56 ±8.38 μmol/L, 1.43± 0.53μmol/mL vs 1.81 ±0.42 μmol/mL, 4.00± 0.54 μg/mL vs 4.88 ± 0.77 pg/mL respectively, P 〈 0.05). The morphology of the intestinal mucosa showed destroyed villi in LPS group and atrophied intestinal mucosa in other groups. The pathological intestinal mucosal changes were less in LPS + Lianshu group than in LPS group. The number of IgA+ plasma cells and amount of SIgA were higher in LPS + Lianshu group than in LPS group (1.16±0.19/μm^2 vs 1.09±0.28/μm^2, P = 0.026; 0.59 ±0.12 mg/L vs 0.15± 0.19 mg/L respectively, P = 0.000). Lianshu had counteractive effects on yeast-induced pyrexia and enterokinesia in rats. CONCLUSION: Lianshu preparation has therapeutic effects on LPS-induced diarrhea and enterokinesia in rats.展开更多
BACKGROUND: Remote organ failure occurs in cases of acute pancreatitis (AP); however, the reports on AP induced by pancreatic duct obstruction are rare. In this study we determined the effect of L-cysteine on pancreat...BACKGROUND: Remote organ failure occurs in cases of acute pancreatitis (AP); however, the reports on AP induced by pancreatic duct obstruction are rare. In this study we determined the effect of L-cysteine on pancreaticobiliary inflammation and remote organ damage in rats after pancreaticobiliary duct ligation (PBDL). METHODS: AP was induced by PBDL in rats with 5/0 silk Sixty rats were randomly divided into 4 groups. Groups A and B were sham-operated groups that received injections of saline or L-cysteine (10 mg/kg) intraperitoneally (15 rats in each group). Groups C and D were PBDL groups that received injections of saline or L-cysteine (10 mg/kg) intraperitoneally (15 rats in each group). The tissue samples of the pancreas and remote organs such as the lung, liver, intestine and kidney were subsequently examined for pathological changes under a light microscope. The samples were also stored for the determination of malondialdehyde and glutathione levels. Blood urea nitrogen (BUN), plasma amylase, ALT and AST levels were determined spectrophotometrically using an automated analyzer. Also, we evaluated the effect of L-cysteine on remote organ injury in rats with AP induced by retrograde infusion of 3.5% sodium taurocholate (NaTc) into the bile-pancreatic duct. RESULTS: Varying degrees of injury in the pancreas, lung, liver intestine and kidney were observed in the rats 24 hours after PBDL. The severity of injury to the lung, liver and intestine was attenuated, while injury status was not changed significantly in the pancreas and kidney after L-cysteine treatment. Oxidativestress was also affected by L-cysteine in PBDL-treated rats. The concentration of tissue malondialdehyde decreased in the pancreas and remote organs of PBDL and L-cysteine administrated rats, and the concentration of glutathione increased more significantly than that of the model control group. However, L-cysteine administration reduced the severity of injury in remote organs but not in the pancreas in rats with NaTc-induced AP. CONCLUSION: L-cysteine treatment attenuated multiple organ damage at an early stage of AP in rats and modulated the oxidant/antioxidant imbalance.展开更多
BACKGROUND Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma(PDAC)in order to improve their chances of survival.Recent studies have shown potent...BACKGROUND Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma(PDAC)in order to improve their chances of survival.Recent studies have shown potent anti-neoplastic effects of curcumin and its analogues.In addition,the role of histone methyltransferases on cancer therapeutics has also been elucidated.However,the relationship between these two factors in the treatment of pancreatic cancer remains unknown.Our working hypothesis was that L48H37,a novel curcumin analog,has better efficacy in pancreatic cancer cell growth inhibition in the absence of histonelysine N-methyltransferase 2D(KMT2D).AIM To determine the anti-cancer effects of L48H37 in PDAC,and the role of KMT2D on its therapeutic efficacy.METHODS The viability and proliferation of primary(PANC-1 and MIA PaCa-2)and metastatic(SW1990 and ASPC-1)PDAC cell lines treated with L48H37 was determined by CCK8 and colony formation assay.Apoptosis,mitochondrial membrane potential(MMP),reactive oxygen species(ROS)levels,and cell cycle profile were determined by staining the cells with Annexin-V/7-AAD,JC-1,DCFH-DA,and PI respectively,as well as flow cytometric acquisition.In vitro migration was assessed by the wound healing assay.The protein and mRNA levels of relevant factors were analyzed using Western blotting,immunofluorescence and real time-quantitative PCR.The in situ expression of KMT2D in both human PDAC and paired adjacent normal tissues was determined by immunohistochemistry.In vivo tumor xenografts were established by injecting nude mice with PDAC cells.Bioinformatics analyses were also conducted using gene expression databases and TCGA.RESULTS L48H37 inhibited the proliferation and induced apoptosis in SW1990 and ASPC-1 cells in a dose-and time-dependent manner,while also reducing MMP,increasing ROS levels,arresting cell cycle at the G2/M stages and activating the endoplasmic reticulum(ER)stress-associated protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4(ATF4)/CHOP signaling pathway.Knocking down ATF4 significantly upregulated KMT2D in PDAC cells,and also decreased L48H37-induced apoptosis.Furthermore,silencing KMT2D in L48H37-treated cells significantly augmented apoptosis and the ER stress pathway,indicating that KMT2D depletion is essential for the anti-neoplastic effects of L48H37.Administering L48H37 to mice bearing tumors derived from control or KMT2Dknockdown PDAC cells significantly decreased the tumor burden.We also identified several differentially expressed genes in PDAC cell lines expressing very low levels of KMT2D that were functionally categorized into the extrinsic apoptotic signaling pathway.The KMT2D high-and low-expressing PDAC patients from the TCGA database showed similar survival rates,but higher KMT2D expression was associated with poor tumor grade in clinical and pathological analyses.CONCLUSION L48H37 exerts a potent anti-cancer effect in PDAC,which is augmented by KMT2D deficiency.展开更多
In the western and central Pacific Ocean,upper strata waters exhibit highly dynamic oceanographic features under ENSO variability.This has been proved to be responsible for the dynamic change of both abundance and zon...In the western and central Pacific Ocean,upper strata waters exhibit highly dynamic oceanographic features under ENSO variability.This has been proved to be responsible for the dynamic change of both abundance and zonal distribution of skipjack tuna(Katsuwonus pelamis).Although causality has been suggested by researchers using physical-biological interaction models,cumulative evidence needs to be obtained and the tenability of assertion needs to be tested from an ecological habitat perspective,based on fisheries data.For purse seine fishery,the use of catch per unit effort(CPUE)as an indication of the abundance is confusing because of technical improvements over the whole exploitation history and unbalanced individual fishing characteristic of vessels.It is particularly interesting to discriminate between habitat characteristics in comparative scenarios of CPUE application.This study identified habitat traits based on a series of oceanographic factors from a global ocean reanalysis model.A comparison was conducted between two habitat models based on unprocessed purse seine CPUE and standardized CPUE considering fishing characteristics.The results suggest that standardized CPUE could model the regular zonal shift of habitat compatible with the observed fishing efforts transfer,and achieved better prediction capacity than unprocessed CPUE.Furthermore,the habitat of skipjack tuna was also characterized and linked with surface and subsurface thermal environment,ocean current,dissolved oxygen,biotic environment,and ENSO variability.The monthly-averaged habitat suitable index,derived from the optimal habitat model prediction,showed a significant linear relationship with the southern oscillation index,which suggested that El Ni?o episodes eventually provide more preferable habitat for skipjack tuna under ENSO variability.展开更多
采用氩气雾化法制备了Ti60CuNiCr合金钎料粉末,表征了细粉的收得率、微观形貌、组织和成分,研究了该钎料粉末在纯Ti和Ti2AlNb两种基体上的流动性。结果表明,正200目Ti60Cu Ni Cr合金钎料细粉的收得率大于50%,细粉具有较高的球形度、均...采用氩气雾化法制备了Ti60CuNiCr合金钎料粉末,表征了细粉的收得率、微观形貌、组织和成分,研究了该钎料粉末在纯Ti和Ti2AlNb两种基体上的流动性。结果表明,正200目Ti60Cu Ni Cr合金钎料细粉的收得率大于50%,细粉具有较高的球形度、均匀的成分,以纯Ti相为主,在纯Ti和Ti1AlNb两种基材上均有优异的流动性。展开更多
基金supported by Guangdong Provincial Basic and Applied Basic Research Fund,No.2021A1515011299(to KT)。
文摘Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.
文摘AIM To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis. METHODS A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3'-UTR. MiR-155 mimics, negative controls and SHIP-1 expression/knockdown vectors were established and then utilized in gain-and loss-of-function studies performed in raw264.7 cells and primary bone marrow-derived macrophages (BMDMs). Thereafter, dextran sulfate sodium (DSS)-induced colitis mouse model with or without antagomiR-155 treatment was established, and the levels of miR-155 and SHIP-1, as well as the pro-inflammatory capabilities, were measured by western blot, quantitative polymerase chain reaction, and immunohistochemistry. RESULTS MiR-155 directly bound to the 3'-UTR of SHIP-1 mRNA and induced a significant decrease in SHIP-1 expression in both raw264.7 cells and primary BMDMs. MiR-155 markedly promoted cell proliferation and proinflammatory secretions including IL-6, TNF-alpha, IL-1 beta, and IFN-gamma, whereas these effects could be reversed by the restoration of SHIP-1 expression. In vivo studies showed that antagomiR-155 administration could alleviate DSS-induced intestinal inflammation in Balb/c mice. Moreover, significantly increased SHIP-1 expression, as well as decreased Akt activation and in-flammatory response, were observed in the antagomiR-155-treated mice. CONCLUSION MiR-155 promotes experimental colitis by repressing SHIP-1 expression. Thus, the inhibition of miR-155 might be a promising strategy for therapy.
基金Supported by State Administration of Chinese Medicine,No.04-06LP24Health Bureau of Shanghai,No.06ER14090the Major State Basic Research Development Program of China "973 Program",No.2006CB504810
文摘AIM: To investigate the effect of Lianshu preparation on lipopolysaccharide (LPS)-induced diarrhea in rats. METHODS: A diarrhea model was established in Sprague Dawley rats via injection of 1 mL of 30 mg/kg LPS. A total of 40 rats were randomly divided into normal group, LPS group, LPS + Lianshu group, LPS + berberine group (n = 10 in each group). Their intestinal mucosal barrier and frequency of diarrhea were observed. Levels of glucose, serum Na^+, K^+, Cl and hematocrit, plasma nitrogen monoxide (NO), diamine oxidase (DAO), and D (-)-lactate were measured. The number of IgA+ plasma cells in small intestine was detected and SIgA levels in the intestinal fluid were measured. The antipyretic activity of Lianshu preparation in rats was evaluated using Brewer's yeast-induced pyrexia (10 mL/kg of 20% aqueous suspension). Acetaminophen (250 mg/kg, intragastric administration, bid) was comparison. Temperature used as a standard drug for was recorded 1 h before and 6 h after Brewer's yeast injection. Finally, small intestina transmission in mice treated with Lianshu was detected after intraperitoneal injection of methyl prostigmin (2 mg/kg). Atropine (10 g/kg) was used as a control. The ink content in intestine was determined and the total length of intestine was measured. RESULTS: The frequency of diarrhea was higher in LPS group than in LPS + Lianshu group and LPS + berberine group (36.70± 5.23 vs 28.50 ±4.06 and 32.70±9.30 respectively, P 〈 0.01), and lower in LP5 + Lianshu group than in LPS + berberine group (P = 0.03). The levels of Na+, glucose, Cl, K^+ were significantly lower in LPS + Lianshu group than in LPS + berberine group (140.35±3.19 mmol/L vs 131.99±4.86 mmol/L, 8.49 ±1.84 mmol/L vs 6.54±2.30 mmol/L, 106.29± 4.41 mmol/L vs 102.5±1.39 mmol/L, 5.08±0.66 mmol/L vs 4.32 ± 0.62 mmol/L respectively, P 〈 0.05). The level of hematocrit was lower in LPS + Lianshu group than in LPS + berberine group (0.50% ±0.07% vs 0.59%± 0.10% respectively, P 〈 0.05). The plasma levels of NO, DAO and D (-)-lactate were higher in LPS group than in normal group (79.74 ± 7.39μmol/L vs 24.94 ± 3.38μmol/L, 2.48 ±0.42μ/mL vs 0.82 ±0.33 p/mL, 5.63± 0.85μg/mL vs 2.01 ±0.32 μg/mL respectively, P 〈 0.01), and lower in LPS + Lianshu group than in LP5 + berberine group (48.59±4.70μmol/L vs 51.56 ±8.38 μmol/L, 1.43± 0.53μmol/mL vs 1.81 ±0.42 μmol/mL, 4.00± 0.54 μg/mL vs 4.88 ± 0.77 pg/mL respectively, P 〈 0.05). The morphology of the intestinal mucosa showed destroyed villi in LPS group and atrophied intestinal mucosa in other groups. The pathological intestinal mucosal changes were less in LPS + Lianshu group than in LPS group. The number of IgA+ plasma cells and amount of SIgA were higher in LPS + Lianshu group than in LPS group (1.16±0.19/μm^2 vs 1.09±0.28/μm^2, P = 0.026; 0.59 ±0.12 mg/L vs 0.15± 0.19 mg/L respectively, P = 0.000). Lianshu had counteractive effects on yeast-induced pyrexia and enterokinesia in rats. CONCLUSION: Lianshu preparation has therapeutic effects on LPS-induced diarrhea and enterokinesia in rats.
基金supported by grants from the National Natural Science Foundation of China(30971359)the Shanghai Key Laboratory of Pancreatic Diseases for open research project(P2012001)
文摘BACKGROUND: Remote organ failure occurs in cases of acute pancreatitis (AP); however, the reports on AP induced by pancreatic duct obstruction are rare. In this study we determined the effect of L-cysteine on pancreaticobiliary inflammation and remote organ damage in rats after pancreaticobiliary duct ligation (PBDL). METHODS: AP was induced by PBDL in rats with 5/0 silk Sixty rats were randomly divided into 4 groups. Groups A and B were sham-operated groups that received injections of saline or L-cysteine (10 mg/kg) intraperitoneally (15 rats in each group). Groups C and D were PBDL groups that received injections of saline or L-cysteine (10 mg/kg) intraperitoneally (15 rats in each group). The tissue samples of the pancreas and remote organs such as the lung, liver, intestine and kidney were subsequently examined for pathological changes under a light microscope. The samples were also stored for the determination of malondialdehyde and glutathione levels. Blood urea nitrogen (BUN), plasma amylase, ALT and AST levels were determined spectrophotometrically using an automated analyzer. Also, we evaluated the effect of L-cysteine on remote organ injury in rats with AP induced by retrograde infusion of 3.5% sodium taurocholate (NaTc) into the bile-pancreatic duct. RESULTS: Varying degrees of injury in the pancreas, lung, liver intestine and kidney were observed in the rats 24 hours after PBDL. The severity of injury to the lung, liver and intestine was attenuated, while injury status was not changed significantly in the pancreas and kidney after L-cysteine treatment. Oxidativestress was also affected by L-cysteine in PBDL-treated rats. The concentration of tissue malondialdehyde decreased in the pancreas and remote organs of PBDL and L-cysteine administrated rats, and the concentration of glutathione increased more significantly than that of the model control group. However, L-cysteine administration reduced the severity of injury in remote organs but not in the pancreas in rats with NaTc-induced AP. CONCLUSION: L-cysteine treatment attenuated multiple organ damage at an early stage of AP in rats and modulated the oxidant/antioxidant imbalance.
文摘BACKGROUND Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma(PDAC)in order to improve their chances of survival.Recent studies have shown potent anti-neoplastic effects of curcumin and its analogues.In addition,the role of histone methyltransferases on cancer therapeutics has also been elucidated.However,the relationship between these two factors in the treatment of pancreatic cancer remains unknown.Our working hypothesis was that L48H37,a novel curcumin analog,has better efficacy in pancreatic cancer cell growth inhibition in the absence of histonelysine N-methyltransferase 2D(KMT2D).AIM To determine the anti-cancer effects of L48H37 in PDAC,and the role of KMT2D on its therapeutic efficacy.METHODS The viability and proliferation of primary(PANC-1 and MIA PaCa-2)and metastatic(SW1990 and ASPC-1)PDAC cell lines treated with L48H37 was determined by CCK8 and colony formation assay.Apoptosis,mitochondrial membrane potential(MMP),reactive oxygen species(ROS)levels,and cell cycle profile were determined by staining the cells with Annexin-V/7-AAD,JC-1,DCFH-DA,and PI respectively,as well as flow cytometric acquisition.In vitro migration was assessed by the wound healing assay.The protein and mRNA levels of relevant factors were analyzed using Western blotting,immunofluorescence and real time-quantitative PCR.The in situ expression of KMT2D in both human PDAC and paired adjacent normal tissues was determined by immunohistochemistry.In vivo tumor xenografts were established by injecting nude mice with PDAC cells.Bioinformatics analyses were also conducted using gene expression databases and TCGA.RESULTS L48H37 inhibited the proliferation and induced apoptosis in SW1990 and ASPC-1 cells in a dose-and time-dependent manner,while also reducing MMP,increasing ROS levels,arresting cell cycle at the G2/M stages and activating the endoplasmic reticulum(ER)stress-associated protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4(ATF4)/CHOP signaling pathway.Knocking down ATF4 significantly upregulated KMT2D in PDAC cells,and also decreased L48H37-induced apoptosis.Furthermore,silencing KMT2D in L48H37-treated cells significantly augmented apoptosis and the ER stress pathway,indicating that KMT2D depletion is essential for the anti-neoplastic effects of L48H37.Administering L48H37 to mice bearing tumors derived from control or KMT2Dknockdown PDAC cells significantly decreased the tumor burden.We also identified several differentially expressed genes in PDAC cell lines expressing very low levels of KMT2D that were functionally categorized into the extrinsic apoptotic signaling pathway.The KMT2D high-and low-expressing PDAC patients from the TCGA database showed similar survival rates,but higher KMT2D expression was associated with poor tumor grade in clinical and pathological analyses.CONCLUSION L48H37 exerts a potent anti-cancer effect in PDAC,which is augmented by KMT2D deficiency.
基金The National Key R&D Program of China under contract Nos 2020YFD0901202 and 2019YFD0901502the National Natural Science Foundation of China under contract Nos 41806110,41506151 and 31902426。
文摘In the western and central Pacific Ocean,upper strata waters exhibit highly dynamic oceanographic features under ENSO variability.This has been proved to be responsible for the dynamic change of both abundance and zonal distribution of skipjack tuna(Katsuwonus pelamis).Although causality has been suggested by researchers using physical-biological interaction models,cumulative evidence needs to be obtained and the tenability of assertion needs to be tested from an ecological habitat perspective,based on fisheries data.For purse seine fishery,the use of catch per unit effort(CPUE)as an indication of the abundance is confusing because of technical improvements over the whole exploitation history and unbalanced individual fishing characteristic of vessels.It is particularly interesting to discriminate between habitat characteristics in comparative scenarios of CPUE application.This study identified habitat traits based on a series of oceanographic factors from a global ocean reanalysis model.A comparison was conducted between two habitat models based on unprocessed purse seine CPUE and standardized CPUE considering fishing characteristics.The results suggest that standardized CPUE could model the regular zonal shift of habitat compatible with the observed fishing efforts transfer,and achieved better prediction capacity than unprocessed CPUE.Furthermore,the habitat of skipjack tuna was also characterized and linked with surface and subsurface thermal environment,ocean current,dissolved oxygen,biotic environment,and ENSO variability.The monthly-averaged habitat suitable index,derived from the optimal habitat model prediction,showed a significant linear relationship with the southern oscillation index,which suggested that El Ni?o episodes eventually provide more preferable habitat for skipjack tuna under ENSO variability.
文摘采用氩气雾化法制备了Ti60CuNiCr合金钎料粉末,表征了细粉的收得率、微观形貌、组织和成分,研究了该钎料粉末在纯Ti和Ti2AlNb两种基体上的流动性。结果表明,正200目Ti60Cu Ni Cr合金钎料细粉的收得率大于50%,细粉具有较高的球形度、均匀的成分,以纯Ti相为主,在纯Ti和Ti1AlNb两种基材上均有优异的流动性。