Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular ca...Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (HCC). The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-α (TNF-α) and suppressor of cytokine signaling 3 (SOC-3). IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis and even HCC. In addition, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon.展开更多
The special topic of the two papers is the systemic acquired resistance （SAR） and pathogenesis-related protein genes （PR）. SAR is an enhanced resistance against further potential parasite beyond the initial infect...The special topic of the two papers is the systemic acquired resistance （SAR） and pathogenesis-related protein genes （PR）. SAR is an enhanced resistance against further potential parasite beyond the initial infection site, which can be induced by either pathogen infection or exogenous inducer, including synthetic chemicals and natural prod- ucts. As a ＂whole-plant＂ resistance defense, SAR confers broad-spectrum immunity to widely diverse pathogenic microorganisms, such as viruses, bacteria and fungi for a relatively long lasting period. Convincingly, it is a promising way to prevent crop diseases by activating the plants＇ own natural defenses via application of chemical inducers or creating resistant wheat cultivars.展开更多
Alzheimer＇s disease（AD） is characterized by amyloid-b（Ab） toxicity,tau pathology,insulin resistance,neuroinflammation,and dysregulation of cholesterol homeostasis,all of which play roles in neurodegeneration.Insu...Alzheimer＇s disease（AD） is characterized by amyloid-b（Ab） toxicity,tau pathology,insulin resistance,neuroinflammation,and dysregulation of cholesterol homeostasis,all of which play roles in neurodegeneration.Insulin has polytrophic effects on neurons and may be at the center of these pathophysiological changes.In this study,we investigated possible relationships among insulin signaling and cholesterol biosynthesis,along with the effects of Ab42 on these pathways in vitro.We found that neuroblastoma 2a（N2a） cells transfected with the human gene encoding amyloid-b protein precursor（Ab PP）（N2aAb PP） produced Ab and exhibited insulin resistance by reduced p-Akt and a suppressed cholesterol-synthesis pathway following insulin treatment,and by increased phosphorylation of insulin receptor subunit-1 at serine 612（p-IRS-S612） as compared to parental N2 a cells.Treatment of human neuroblastoma SH-SY5 Y cells with Ab42 also increased p-IRS-S612,suggesting that Ab42 is responsible for insulin resistance.The insulin resistance was alleviated when N2a-Ab PP cells were treated with higher insulin concentrations.Insulin increased Ab release from N2 aAb PP cells,by which it may promote Ab clearance.Insulin increased cholesterol-synthesis gene expression in SHSY5 Y and N2 a cells,including 24-dehydrocholesterol reductase（DHCR24） and 3-hydroxy-3-methyl-glutaryl-Co A reductase（HMGCR） through sterol-regulatory element-binding protein-2（SREBP2）.While Ab42-treated SH-SY5 Y cells exhibited increased HMGCR expression and c-Jun phosphorylation as pro-inflammatory responses,they also showed down-regulation of neuro-protective/antiinflammatory DHCR24.These results suggest that Ab42 may cause insulin resistance,activate JNK for c-Jun phosphorylation,and lead to dysregulation of cholesterol homeostasis,and that enhancing insulin signaling may relieve the insulin-resistant phenotype and the dysregulated cholesterol-synthesis pathway to promote Ab release for clearance from neural cells.展开更多
Fabric-based pressure sensors offer high stability,low energy consumption,and excellent wearing com-fort,making them promise intelligent wearable devices and health monitoring.However,creating a fabric-based capacitiv...Fabric-based pressure sensors offer high stability,low energy consumption,and excellent wearing com-fort,making them promise intelligent wearable devices and health monitoring.However,creating a fabric-based capacitive pressure sensor that integrates high sensitivity,wide detection range,good air breathability,water vapour permeability,and low cost remains a challenge.In this study,a sensor two-scale synergistic resistive/capacitive hybrid response model is developed to analyze the sensor response factors at different pressing stages.It is proposed that fabric metal silver electrodes be prepared using the microdroplet jetting technology,combined with the sacrificial template method and mixed doping of active materials to prepare the dielectric layer.Results indicate the sensor achieves a high sensitivity of 2.872 kPa^(−1)within a pressure range of 0-1 kPa,with an average air breathability of 61.69 mm/s and water vapour permeability of 3075.01 g/m^(2)24 h.Its applications in human motion monitoring and human-computer interaction highlight its potential in wearable technology.展开更多
Aging is closely related to redox regulation.In our previous work,we proposed a new concept,“redox-stress response capacity(RRC),”and found that the decline in RRC was a dynamic characteristic of aging.However,the m...Aging is closely related to redox regulation.In our previous work,we proposed a new concept,“redox-stress response capacity(RRC),”and found that the decline in RRC was a dynamic characteristic of aging.However,the mechanism of RRC decline during aging remains unknown.In this study,using the senescent human fibroblast cell model and Caenorhabditis elegans model,we identified that peroxiredoxin 2(PRDX2),as a hydrogen peroxide(H_(2)O_(2))sensor,was involved in mediating RRC.PRDX2 knockdown led to a decline of RRC and accelerated senescence in fibroblasts and prdx-2 mutant C.elegans also showed decreased RRC.The mechanism study showed that the decreased sensor activity of PRDX2 was related to the increase in hyperoxidation of PRDX2 in senescent cells.Moreover,the level of PRDX2 hyperoxidation also increased in old C.elegans.Simultaneous overexpression of both PRDX2 and sulfiredoxin(SRX)rescued the reduced RRC and delayed senescence.The increase in PRDX2 hyperoxidation in senescent cells led to a decrease in its sensor activity,resulting in the decreased cellular response to H_(2)O_(2),which is similar to the mechanism of insulin resistance due to the lower insulin receptor sensitivity.Treatment of young cells with a high level of H_(2)O_(2)to induce a higher level of PRDX2-SO_(3) resulted in mimicking the RRC decline in senescent cells,which is also similar to a model of insulin resistance induced by high levels of insulin.All these results thrillingly indicate that there is an insulin-resistance-like phenomenon in senescent cells,we named it redox-stress response resistance,RRR.RRR in senescent cells is an important new discovery that explains RRC decline during aging and reveals the internal relationship between redox regulation and aging from a new perspective.展开更多
A unique optoelectronic synaptic device has been developed,leveraging the negative photoconductance property of a single-crystal material system called Cs2CoCl4.This device exhibits a simultaneous volatile resistive s...A unique optoelectronic synaptic device has been developed,leveraging the negative photoconductance property of a single-crystal material system called Cs2CoCl4.This device exhibits a simultaneous volatile resistive switching response and sensitivity to optical stimuli,positioning Cs2CoCl4 as a promising candidate for optically enhanced neuromorphicapplications.展开更多
文摘Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (HCC). The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-α (TNF-α) and suppressor of cytokine signaling 3 (SOC-3). IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis and even HCC. In addition, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon.
文摘The special topic of the two papers is the systemic acquired resistance （SAR） and pathogenesis-related protein genes （PR）. SAR is an enhanced resistance against further potential parasite beyond the initial infection site, which can be induced by either pathogen infection or exogenous inducer, including synthetic chemicals and natural prod- ucts. As a ＂whole-plant＂ resistance defense, SAR confers broad-spectrum immunity to widely diverse pathogenic microorganisms, such as viruses, bacteria and fungi for a relatively long lasting period. Convincingly, it is a promising way to prevent crop diseases by activating the plants＇ own natural defenses via application of chemical inducers or creating resistant wheat cultivars.
基金supported by CIHR Grants (109606,106886,and TAD 125698)an Ontario Graduate Scholarship,an Admission Scholarship,and an Excellence Scholarship from the University of Ottawa
文摘Alzheimer＇s disease（AD） is characterized by amyloid-b（Ab） toxicity,tau pathology,insulin resistance,neuroinflammation,and dysregulation of cholesterol homeostasis,all of which play roles in neurodegeneration.Insulin has polytrophic effects on neurons and may be at the center of these pathophysiological changes.In this study,we investigated possible relationships among insulin signaling and cholesterol biosynthesis,along with the effects of Ab42 on these pathways in vitro.We found that neuroblastoma 2a（N2a） cells transfected with the human gene encoding amyloid-b protein precursor（Ab PP）（N2aAb PP） produced Ab and exhibited insulin resistance by reduced p-Akt and a suppressed cholesterol-synthesis pathway following insulin treatment,and by increased phosphorylation of insulin receptor subunit-1 at serine 612（p-IRS-S612） as compared to parental N2 a cells.Treatment of human neuroblastoma SH-SY5 Y cells with Ab42 also increased p-IRS-S612,suggesting that Ab42 is responsible for insulin resistance.The insulin resistance was alleviated when N2a-Ab PP cells were treated with higher insulin concentrations.Insulin increased Ab release from N2 aAb PP cells,by which it may promote Ab clearance.Insulin increased cholesterol-synthesis gene expression in SHSY5 Y and N2 a cells,including 24-dehydrocholesterol reductase（DHCR24） and 3-hydroxy-3-methyl-glutaryl-Co A reductase（HMGCR） through sterol-regulatory element-binding protein-2（SREBP2）.While Ab42-treated SH-SY5 Y cells exhibited increased HMGCR expression and c-Jun phosphorylation as pro-inflammatory responses,they also showed down-regulation of neuro-protective/antiinflammatory DHCR24.These results suggest that Ab42 may cause insulin resistance,activate JNK for c-Jun phosphorylation,and lead to dysregulation of cholesterol homeostasis,and that enhancing insulin signaling may relieve the insulin-resistant phenotype and the dysregulated cholesterol-synthesis pathway to promote Ab release for clearance from neural cells.
基金financially supported by the China Postdoctoral Science Foundation(No.2023M732827)the Natural Science Basic Research Program of Shaanxi(No.2023-JC-QN-0510)+2 种基金the Scientific Research Program Funded by Shaanxi Provincial Education Depart-ment(No.21JK0649)the Scientific Research Foundation for Doctor of Xi’an Polytechnic University(No.BS202057)the Innova-tion Foundation for Graduate of Xi’an Polytechnic University(No.chx2024007).
文摘Fabric-based pressure sensors offer high stability,low energy consumption,and excellent wearing com-fort,making them promise intelligent wearable devices and health monitoring.However,creating a fabric-based capacitive pressure sensor that integrates high sensitivity,wide detection range,good air breathability,water vapour permeability,and low cost remains a challenge.In this study,a sensor two-scale synergistic resistive/capacitive hybrid response model is developed to analyze the sensor response factors at different pressing stages.It is proposed that fabric metal silver electrodes be prepared using the microdroplet jetting technology,combined with the sacrificial template method and mixed doping of active materials to prepare the dielectric layer.Results indicate the sensor achieves a high sensitivity of 2.872 kPa^(−1)within a pressure range of 0-1 kPa,with an average air breathability of 61.69 mm/s and water vapour permeability of 3075.01 g/m^(2)24 h.Its applications in human motion monitoring and human-computer interaction highlight its potential in wearable technology.
基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB39000000)the National Key Research and Development Program of China(2022YFA1303000,2022YFA1305100,2017YFA0504000)the National Natural Science Foundation of China(91849203)。
文摘Aging is closely related to redox regulation.In our previous work,we proposed a new concept,“redox-stress response capacity(RRC),”and found that the decline in RRC was a dynamic characteristic of aging.However,the mechanism of RRC decline during aging remains unknown.In this study,using the senescent human fibroblast cell model and Caenorhabditis elegans model,we identified that peroxiredoxin 2(PRDX2),as a hydrogen peroxide(H_(2)O_(2))sensor,was involved in mediating RRC.PRDX2 knockdown led to a decline of RRC and accelerated senescence in fibroblasts and prdx-2 mutant C.elegans also showed decreased RRC.The mechanism study showed that the decreased sensor activity of PRDX2 was related to the increase in hyperoxidation of PRDX2 in senescent cells.Moreover,the level of PRDX2 hyperoxidation also increased in old C.elegans.Simultaneous overexpression of both PRDX2 and sulfiredoxin(SRX)rescued the reduced RRC and delayed senescence.The increase in PRDX2 hyperoxidation in senescent cells led to a decrease in its sensor activity,resulting in the decreased cellular response to H_(2)O_(2),which is similar to the mechanism of insulin resistance due to the lower insulin receptor sensitivity.Treatment of young cells with a high level of H_(2)O_(2)to induce a higher level of PRDX2-SO_(3) resulted in mimicking the RRC decline in senescent cells,which is also similar to a model of insulin resistance induced by high levels of insulin.All these results thrillingly indicate that there is an insulin-resistance-like phenomenon in senescent cells,we named it redox-stress response resistance,RRR.RRR in senescent cells is an important new discovery that explains RRC decline during aging and reveals the internal relationship between redox regulation and aging from a new perspective.
文摘A unique optoelectronic synaptic device has been developed,leveraging the negative photoconductance property of a single-crystal material system called Cs2CoCl4.This device exhibits a simultaneous volatile resistive switching response and sensitivity to optical stimuli,positioning Cs2CoCl4 as a promising candidate for optically enhanced neuromorphicapplications.
