Colorectal cancer is the third most common cancer worldwide. Metastasis is a major cause of colorectal cancer-related death. Mechanisms of metastasis remain largely obscure. MicroRNA is one of the most important epige...Colorectal cancer is the third most common cancer worldwide. Metastasis is a major cause of colorectal cancer-related death. Mechanisms of metastasis remain largely obscure. MicroRNA is one of the most important epigenetic regulators by targeting mRNAs posttranscriptionally. Accumulated evidence has supported its significant role in the metastasis of colorectal cancer, including epithelial-mesenchymal transition and angiogenesis. Dissecting microRNAome potentially identifies specific microRNAs as biomarkers of colorectal cancer metastasis. Better understanding of the complex network of microRNAs in colorectal cancer metastasis provide new insights in the biological process of metastasis and in the potential targets for colorectal cancer therapies and for diagnosis of recurrent and metastatic colorectal cancer.展开更多
Quiescent state has been observed in stem cells(SCs),including in adult SCs and in cancer SCs(CSCs).Quiescent status of SCs contributes to SC self-renewal and conduces to averting SC death from harsh external stimuli....Quiescent state has been observed in stem cells(SCs),including in adult SCs and in cancer SCs(CSCs).Quiescent status of SCs contributes to SC self-renewal and conduces to averting SC death from harsh external stimuli.In this review,we provide an overview of intrinsic mechanisms and extrinsic factors that regulate adult SC quiescence.The intrinsic mechanisms discussed here include the cell cycle,mitogenic signaling,Notch signaling,epigenetic modification,and metabolism and transcriptional regulation,while the extrinsic factors summarized here include microenvironment cells,extracellular factors,and immune response and inflammation in microenvironment.Quiescent state of CSCs has been known to contribute immensely to therapeutic resistance in multiple cancers.The characteristics and the regulation mechanisms of quiescent CSCs are discussed in detail.Importantly,we also outline the recent advances and controversies in therapeutic strategies targeting CSC quiescence.展开更多
An efficient electrocatalyst is indispensable to significantly reduce energy consumption and accelerate the conversion efficiency of water splitting.In this work,the honeycomb-like porous MoCo alloy on nitrogen-doped ...An efficient electrocatalyst is indispensable to significantly reduce energy consumption and accelerate the conversion efficiency of water splitting.In this work,the honeycomb-like porous MoCo alloy on nitrogen-doped three-dimensional(3D)porous graphene substrate(Mo_(0.3)Co_(0.7)@NPG)has been synthesized from the annealing of layered double hydroxide(MoCo-LDH@NPG).Especially,the Mo_(0.3)Co_(0.7)@NPG exhibits low hydrogen evolution overpotential of 75 mV(10 mA·cm^(-2))and a Tafel slope of 69.9 mV·dec^(-1),which can be attributed to highly conductive NPG substrate,the unique nanostructure and the synergistic effect of Mo and Co.Moreover,the Mo_(0.3)Co_(0.7)@NPG can maintain the original morphology and high catalytic activity after 50-h stability test.This work proposes a general strategy to synthesize a multi-element alloy on conductive substrates with high porosity for electrocatalytic reaction.展开更多
Compared with physical models,WRF-Solar,as an excellent numerical forecasting model,includes abundant novel cloud physical and dynamical processes,which enablesenable the high-frequency output of radiation components ...Compared with physical models,WRF-Solar,as an excellent numerical forecasting model,includes abundant novel cloud physical and dynamical processes,which enablesenable the high-frequency output of radiation components which are urgently needed by the solar energy industry.However,the popularisation of WRF-Solar in a wide range of applications,such as the estimation of diffuse radiation,suffers from unpredictable influences of cloud and aerosol optical property parameters.This study assessed the accuracy of the improved numerical weather prediction(WRF-Solar)model in simulating global and diffuse radiation.Aerosol optical properties at 550 nm,which were provided by a moderate resolution imaging spectroradiometer,were used as input to analyse the differences in accuracies obtained by the model with/without aerosol input.The sensitivity of WRF-Solar to aerosol and cloud optical properties and solar zenith angle(SZA)was analysed.The results show the superiority of WRF-Solar to WRF-Dudhia in terms of their root mean square error(RMSE)and mean absolute error(MAE).The coefficients of determination between WRF-Solar and WRF-Dudhia revealed no statistically significant difference,with values greater than 0.9 for the parent and nested domains.In addition,the relative RMSE(RRMSE%)reached 46.60%.The experiment on WRF-Solar and WRF-Dudhia revealed a negative bias for global radiation,but WRF-Solar attained a slightly lower RMSE and higher correlation coefficient than WRF-Dudhia.The WRF-Solar-simulated results on diffuse radiation under clear sky conditions were slightly poorer,with RMSE,RRMSE,mean percentage error and MAE of 181.93 W m^(−2),170.52%,93.04%and 138 W m^(−2),respectively.Based on Himawari-8 cloud data,statistical results on cloud optical thickness(COT)for cloudy days revealed that WRF-Solar overestimated diffuse radiation at COTs greater than 20.Moreover,when the aerosol optical depth was greater than or equal to 0.8,WRF-Solar also overestimated the diffuse radiation,with a mean difference of 58.57 W m^(−2).The errors of WRF-Solar simulations in global and diffuse radiation exhibited a significant dependence on the SZA.The dispersion degree of deviation increased gradually with the decrease in the SZA.Thus,WRF-Solar serves as an improved numerical tool that can provide high temporal and high-spatial-resolution solar radiation data for the prediction of photovoltaic power.Studies should explore the improvement of cumulus parameterisation schemes to enhance the accuracy of solar radiation component estimation and prediction under cloudy conditions.展开更多
Background: Resolvin D1 (RvD1) is a newly found anti-inflammatory bioactive compound derived from polyunsaturated fatty acids. The current study aimed to explore the protective effect of RvD1 on lipopolysaccharide ...Background: Resolvin D1 (RvD1) is a newly found anti-inflammatory bioactive compound derived from polyunsaturated fatty acids. The current study aimed to explore the protective effect of RvD1 on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and its possible mechanism. Methods: Both in vivo and in vitro studies were conducted. Male BALB/c mice were randomly divided into control group (saline), LPS group (LPS 5 mg/kg), RvD1 group (RvD1 5 μg/kg + LPS 5 mg/kg), and blockage group (Boc-MLP 5 gg/kg + RvD1 5 gg/kg + LPS 5 mg/kg). Boc-MLP is a RvD 1 receptor blocker. The mice were intraperitoneally injected with these drugs and recorded for general condition for 48 h, while the blood and kidneys were harvested at 2, 6, 12, 24, and 48 h time points, respectively (n = 6 in each group at each time point). Human proximal tubule epithelial cells (HK-2) were randomly divided into control group (medium only), LPS group (LPS 5 μg/ml), RvD1 group (RvD1 10 ng/ml + LPS 5 μg/ml), and blockage group (Boc-MLP 10 ng/ml + RvD1 10 ng/ml + LPS 5 μg/ml). The cells were harvested for RNA at 2, 4, 6, 12, and 24 h time points, respectively (n = 6 in each group at each time point). Blood creatinine was tested by using an Abbott i-STAT portable blood gas analyzer. Tumor necrosis factor-α (TNF-α level was detected by EL1SA. Kidney pathology was observed under hematoxylin and eosin (HE) staining and transmission electron microscope (TEM). We hired immune-histological staining, Western blotting, and fluorescence quantitative polymerase chain reaction to detect the expression of RvD1 receptor ALX, nuclear factor-kappa B (NF-KB) signaling pathway as well as caspase-3. Kidney apoptosis was evaluated by TUNEL staining. Results: RvD 1 receptor ALX was detected on renal tubular epithelials. Kaplan-Meier analysis indicated that RvD 1 improved 48 h animal survival (80%) compared with LPS group (40%) and RvDI blockage group (60%), while RvD1 also ameliorated kidney pathological injury in HE staining and TEM scan. After LPS stimulation, the mRNA expression of toll-like receptor 4, myeloid differentiation factor 88, and TNF-α in both mice kidneys and HK-2 cells were all up-regulated, while RvDI substantially inhibited the up-regulation of these genes. Western blotting showed that the phosphorylated-IKB/IKB ratio in LPS group was significantly higher than that in the control group, which was inhibited in the RvD1 group. RvD1 could inhibit the up-regulation of cleaved-caspase-3 protein stimulated by LPS, which was prohibited in RvD 1 blockage group. RvD 1 group also had a lower proportion of apoptotic nuclei in mice kidney by TUNEL staining compared with LPS group. Conclusion: In LPS-induced AKI, RvD1 could decrease TNF-α level, ameliorate kidney pathological injury, protect kidney function, and improve animal survival by down-regulating NF-KB inflammatory signal as well as inhibiting renal cell apoptosis.展开更多
Background:Acute kidney injury (AKI) is the most common and life-threatening systemic complication ofrhabdomyolysis.Inflammation plays an important role in the development of rhabdomyolysis-induced AKI.This study a...Background:Acute kidney injury (AKI) is the most common and life-threatening systemic complication ofrhabdomyolysis.Inflammation plays an important role in the development of rhabdomyolysis-induced AKI.This study aimed to investigate the kidney model of AKI caused by rhabdomyolysis to verify the role ofmacrophage Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway.Methods:C57BL/6 mice were injected with a 50% glycerin solution at bilateral back limbs to induce rhabdomyolysis,and CLI-095 or pyrrolidine dithiocarbamate (PDTC) was intraperitoneally injected at 0.5 h before molding.Serum creatinine levels,creatine kinase,the expression of tumor necrosis factor (TNF)-c,interleukin (IL)-1β and I L-6,and hematoxylin and eosin stainings of kidney tissues were tested.The infiltration of macrophage,mRNA levels,and protein expression of TLR4 and NF-κB were investigated by immunofluorescence double-staining techniques,reverse transcriptase-quantitative polymerase chain reaction,and Western blotting,respectively.In vitro,macrophage RAW264.7 was stimulated by ferrous myoglobin;the cytokines,TLR4 and NF-κB expressions were also detected.Results:In an in vivo study,using CLI-095 or PDTC to block TLR4/NF-κB,functional and histologic results showed that the inhibition of TLR4 or NF-κB alleviated glycerol-induced renal damages (P 〈 0.0 1).CLI-095 or PDTC administration suppressed proinflammatory cytokine (TNF-c,IL-6,and IL-1 β) production and macrophage infiltration into the kidney (P 〈 0.01).Moreover,in an in vitro study,CLI-095 or PDTC suppressed myoglobin-induced expression ofTLR4,NF-κB,and proinflammatory cytokine levels in macrophage RAW264.7 cells (P 〈 0.01).Conclusion:The pharmacological inhibition of TLR4/NF-κB exhibited protective effects on rhabdomyolysis-induced AKI by the regulation of proinflammatory cytokine production and macrophage infiltration.展开更多
To the Editor: Congenital diaphragmatic hernia is a congenital anomaly, rarely found in adults. Delayed presentation of congenital diaphragmatic hernia in adults can cause diagnostic dilemma. Immediate laparoscopic re...To the Editor: Congenital diaphragmatic hernia is a congenital anomaly, rarely found in adults. Delayed presentation of congenital diaphragmatic hernia in adults can cause diagnostic dilemma. Immediate laparoscopic repair is recommended for these patients. Here, we presented a case of an 18-year-old man with complaints of chest pain and abdominal discomfort. X-ray and computed tomography (CT) scan revealed a right-sided pleuro-per让oneal hiatus hernia, which is located at postero-lateral diaphragm, also known as Bochdalek hernia.展开更多
基金Supported by NIH K23 CA148964,to Zheng LLefkofsky Family Foundation,to Zheng L+1 种基金the NCI SPORE in Gastrointestinal Cancers P50 CA062924,to Zheng Lthe Zhang Family Gift Fund,to Zheng L
文摘Colorectal cancer is the third most common cancer worldwide. Metastasis is a major cause of colorectal cancer-related death. Mechanisms of metastasis remain largely obscure. MicroRNA is one of the most important epigenetic regulators by targeting mRNAs posttranscriptionally. Accumulated evidence has supported its significant role in the metastasis of colorectal cancer, including epithelial-mesenchymal transition and angiogenesis. Dissecting microRNAome potentially identifies specific microRNAs as biomarkers of colorectal cancer metastasis. Better understanding of the complex network of microRNAs in colorectal cancer metastasis provide new insights in the biological process of metastasis and in the potential targets for colorectal cancer therapies and for diagnosis of recurrent and metastatic colorectal cancer.
文摘Quiescent state has been observed in stem cells(SCs),including in adult SCs and in cancer SCs(CSCs).Quiescent status of SCs contributes to SC self-renewal and conduces to averting SC death from harsh external stimuli.In this review,we provide an overview of intrinsic mechanisms and extrinsic factors that regulate adult SC quiescence.The intrinsic mechanisms discussed here include the cell cycle,mitogenic signaling,Notch signaling,epigenetic modification,and metabolism and transcriptional regulation,while the extrinsic factors summarized here include microenvironment cells,extracellular factors,and immune response and inflammation in microenvironment.Quiescent state of CSCs has been known to contribute immensely to therapeutic resistance in multiple cancers.The characteristics and the regulation mechanisms of quiescent CSCs are discussed in detail.Importantly,we also outline the recent advances and controversies in therapeutic strategies targeting CSC quiescence.
基金supported by the National Natural Science Foundation of China(Nos.52272296 and 51502092)the Fundamental Research Funds for the Central Universities(Nos.JKD01211601 and 1222201718002)the National Overseas High-Level Talent Youth Program in China and the Eastern Scholar Project of Shanghai。
文摘An efficient electrocatalyst is indispensable to significantly reduce energy consumption and accelerate the conversion efficiency of water splitting.In this work,the honeycomb-like porous MoCo alloy on nitrogen-doped three-dimensional(3D)porous graphene substrate(Mo_(0.3)Co_(0.7)@NPG)has been synthesized from the annealing of layered double hydroxide(MoCo-LDH@NPG).Especially,the Mo_(0.3)Co_(0.7)@NPG exhibits low hydrogen evolution overpotential of 75 mV(10 mA·cm^(-2))and a Tafel slope of 69.9 mV·dec^(-1),which can be attributed to highly conductive NPG substrate,the unique nanostructure and the synergistic effect of Mo and Co.Moreover,the Mo_(0.3)Co_(0.7)@NPG can maintain the original morphology and high catalytic activity after 50-h stability test.This work proposes a general strategy to synthesize a multi-element alloy on conductive substrates with high porosity for electrocatalytic reaction.
基金supported by the National Natural Science Foundation of China(41975044,41925007,42371354,42375129,and 41801021)Fundamental Research Funds for National University,China University of Geosciences,Wuhan(CUGDCJJ202201).
文摘Compared with physical models,WRF-Solar,as an excellent numerical forecasting model,includes abundant novel cloud physical and dynamical processes,which enablesenable the high-frequency output of radiation components which are urgently needed by the solar energy industry.However,the popularisation of WRF-Solar in a wide range of applications,such as the estimation of diffuse radiation,suffers from unpredictable influences of cloud and aerosol optical property parameters.This study assessed the accuracy of the improved numerical weather prediction(WRF-Solar)model in simulating global and diffuse radiation.Aerosol optical properties at 550 nm,which were provided by a moderate resolution imaging spectroradiometer,were used as input to analyse the differences in accuracies obtained by the model with/without aerosol input.The sensitivity of WRF-Solar to aerosol and cloud optical properties and solar zenith angle(SZA)was analysed.The results show the superiority of WRF-Solar to WRF-Dudhia in terms of their root mean square error(RMSE)and mean absolute error(MAE).The coefficients of determination between WRF-Solar and WRF-Dudhia revealed no statistically significant difference,with values greater than 0.9 for the parent and nested domains.In addition,the relative RMSE(RRMSE%)reached 46.60%.The experiment on WRF-Solar and WRF-Dudhia revealed a negative bias for global radiation,but WRF-Solar attained a slightly lower RMSE and higher correlation coefficient than WRF-Dudhia.The WRF-Solar-simulated results on diffuse radiation under clear sky conditions were slightly poorer,with RMSE,RRMSE,mean percentage error and MAE of 181.93 W m^(−2),170.52%,93.04%and 138 W m^(−2),respectively.Based on Himawari-8 cloud data,statistical results on cloud optical thickness(COT)for cloudy days revealed that WRF-Solar overestimated diffuse radiation at COTs greater than 20.Moreover,when the aerosol optical depth was greater than or equal to 0.8,WRF-Solar also overestimated the diffuse radiation,with a mean difference of 58.57 W m^(−2).The errors of WRF-Solar simulations in global and diffuse radiation exhibited a significant dependence on the SZA.The dispersion degree of deviation increased gradually with the decrease in the SZA.Thus,WRF-Solar serves as an improved numerical tool that can provide high temporal and high-spatial-resolution solar radiation data for the prediction of photovoltaic power.Studies should explore the improvement of cumulus parameterisation schemes to enhance the accuracy of solar radiation component estimation and prediction under cloudy conditions.
基金This research was supported by a grant of the National Natural Science Foundation of China
文摘Background: Resolvin D1 (RvD1) is a newly found anti-inflammatory bioactive compound derived from polyunsaturated fatty acids. The current study aimed to explore the protective effect of RvD1 on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and its possible mechanism. Methods: Both in vivo and in vitro studies were conducted. Male BALB/c mice were randomly divided into control group (saline), LPS group (LPS 5 mg/kg), RvD1 group (RvD1 5 μg/kg + LPS 5 mg/kg), and blockage group (Boc-MLP 5 gg/kg + RvD1 5 gg/kg + LPS 5 mg/kg). Boc-MLP is a RvD 1 receptor blocker. The mice were intraperitoneally injected with these drugs and recorded for general condition for 48 h, while the blood and kidneys were harvested at 2, 6, 12, 24, and 48 h time points, respectively (n = 6 in each group at each time point). Human proximal tubule epithelial cells (HK-2) were randomly divided into control group (medium only), LPS group (LPS 5 μg/ml), RvD1 group (RvD1 10 ng/ml + LPS 5 μg/ml), and blockage group (Boc-MLP 10 ng/ml + RvD1 10 ng/ml + LPS 5 μg/ml). The cells were harvested for RNA at 2, 4, 6, 12, and 24 h time points, respectively (n = 6 in each group at each time point). Blood creatinine was tested by using an Abbott i-STAT portable blood gas analyzer. Tumor necrosis factor-α (TNF-α level was detected by EL1SA. Kidney pathology was observed under hematoxylin and eosin (HE) staining and transmission electron microscope (TEM). We hired immune-histological staining, Western blotting, and fluorescence quantitative polymerase chain reaction to detect the expression of RvD1 receptor ALX, nuclear factor-kappa B (NF-KB) signaling pathway as well as caspase-3. Kidney apoptosis was evaluated by TUNEL staining. Results: RvD 1 receptor ALX was detected on renal tubular epithelials. Kaplan-Meier analysis indicated that RvD 1 improved 48 h animal survival (80%) compared with LPS group (40%) and RvDI blockage group (60%), while RvD1 also ameliorated kidney pathological injury in HE staining and TEM scan. After LPS stimulation, the mRNA expression of toll-like receptor 4, myeloid differentiation factor 88, and TNF-α in both mice kidneys and HK-2 cells were all up-regulated, while RvDI substantially inhibited the up-regulation of these genes. Western blotting showed that the phosphorylated-IKB/IKB ratio in LPS group was significantly higher than that in the control group, which was inhibited in the RvD1 group. RvD1 could inhibit the up-regulation of cleaved-caspase-3 protein stimulated by LPS, which was prohibited in RvD 1 blockage group. RvD 1 group also had a lower proportion of apoptotic nuclei in mice kidney by TUNEL staining compared with LPS group. Conclusion: In LPS-induced AKI, RvD1 could decrease TNF-α level, ameliorate kidney pathological injury, protect kidney function, and improve animal survival by down-regulating NF-KB inflammatory signal as well as inhibiting renal cell apoptosis.
基金This study was supported by grants from the National Natural Science Foundation of China (No. 81570668, No. 81500524) and the Sichuan Science and Technology Support Program (No. 2015SZ0135).
文摘Background:Acute kidney injury (AKI) is the most common and life-threatening systemic complication ofrhabdomyolysis.Inflammation plays an important role in the development of rhabdomyolysis-induced AKI.This study aimed to investigate the kidney model of AKI caused by rhabdomyolysis to verify the role ofmacrophage Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway.Methods:C57BL/6 mice were injected with a 50% glycerin solution at bilateral back limbs to induce rhabdomyolysis,and CLI-095 or pyrrolidine dithiocarbamate (PDTC) was intraperitoneally injected at 0.5 h before molding.Serum creatinine levels,creatine kinase,the expression of tumor necrosis factor (TNF)-c,interleukin (IL)-1β and I L-6,and hematoxylin and eosin stainings of kidney tissues were tested.The infiltration of macrophage,mRNA levels,and protein expression of TLR4 and NF-κB were investigated by immunofluorescence double-staining techniques,reverse transcriptase-quantitative polymerase chain reaction,and Western blotting,respectively.In vitro,macrophage RAW264.7 was stimulated by ferrous myoglobin;the cytokines,TLR4 and NF-κB expressions were also detected.Results:In an in vivo study,using CLI-095 or PDTC to block TLR4/NF-κB,functional and histologic results showed that the inhibition of TLR4 or NF-κB alleviated glycerol-induced renal damages (P 〈 0.0 1).CLI-095 or PDTC administration suppressed proinflammatory cytokine (TNF-c,IL-6,and IL-1 β) production and macrophage infiltration into the kidney (P 〈 0.01).Moreover,in an in vitro study,CLI-095 or PDTC suppressed myoglobin-induced expression ofTLR4,NF-κB,and proinflammatory cytokine levels in macrophage RAW264.7 cells (P 〈 0.01).Conclusion:The pharmacological inhibition of TLR4/NF-κB exhibited protective effects on rhabdomyolysis-induced AKI by the regulation of proinflammatory cytokine production and macrophage infiltration.
文摘To the Editor: Congenital diaphragmatic hernia is a congenital anomaly, rarely found in adults. Delayed presentation of congenital diaphragmatic hernia in adults can cause diagnostic dilemma. Immediate laparoscopic repair is recommended for these patients. Here, we presented a case of an 18-year-old man with complaints of chest pain and abdominal discomfort. X-ray and computed tomography (CT) scan revealed a right-sided pleuro-per让oneal hiatus hernia, which is located at postero-lateral diaphragm, also known as Bochdalek hernia.