Performance of a scalable quantum processor critically relies on minimizing crosstalk and unwanted interactions within the system,as it is vital for parallel controlled operations on qubits.We present a protocol not o...Performance of a scalable quantum processor critically relies on minimizing crosstalk and unwanted interactions within the system,as it is vital for parallel controlled operations on qubits.We present a protocol not only to provide information about residual coupling but also to effectively discriminate it from the influence of classical crosstalk.Our approach utilizes out-of-time-order correlators(OTOCs)as a signal of quantum crosstalk,making it applicable to various coupling forms and scalable architectures.To demonstrate the effectiveness of our protocol,we provide a theoretical analysis and simulate its implementation in coupled superconducting qubits.展开更多
Synaptic crosstalk is a prevalent phenomenon among neuronal synapses,playing a crucial role in the transmission of neural signals.Therefore,considering synaptic crosstalk behavior and investigating the dynamical behav...Synaptic crosstalk is a prevalent phenomenon among neuronal synapses,playing a crucial role in the transmission of neural signals.Therefore,considering synaptic crosstalk behavior and investigating the dynamical behavior of discrete neural networks are highly necessary.In this paper,we propose a heterogeneous discrete neural network(HDNN)consisting of a three-dimensional KTz discrete neuron and a Chialvo discrete neuron.These two neurons are coupled mutually by two discrete memristors and the synaptic crosstalk is considered.The impact of crosstalk strength on the firing behavior of the HDNN is explored through bifurcation diagrams and Lyapunov exponents.It is observed that the HDNN exhibits different coexisting attractors under varying crosstalk strengths.Furthermore,the influence of different crosstalk strengths on the synchronized firing of the HDNN is investigated,revealing a gradual attainment of phase synchronization between the two discrete neurons as the crosstalk strength decreases.展开更多
Rice(Oryza sativa)plant architecture and grain shape,which determine grain quality and yield,are modulatedby auxin and brassinosteroid via regulation of cell elongation and proliferation.We review the signaltransducti...Rice(Oryza sativa)plant architecture and grain shape,which determine grain quality and yield,are modulatedby auxin and brassinosteroid via regulation of cell elongation and proliferation.We review the signaltransduction of these hormones and the crosstalk between their signals on the regulation of rice plantarchitecture and grain shape.展开更多
As develops in deep sub micron designs,the interconnect crosstalk becomes much more serious.Espe cially, the coupling inductance can not be ignored in gigahertz designs.So shield insertion is an efficient techniq...As develops in deep sub micron designs,the interconnect crosstalk becomes much more serious.Espe cially, the coupling inductance can not be ignored in gigahertz designs.So shield insertion is an efficient technique to reduce the inductive noise.In this paper,the characteristics of on chip mutual inductance (as well as self) for coplanar,micro stripline and stripline structures are introduced first.Then base on the coplanar interconnect structures,the effective coupling K eff model and the RLC explicit noise model are proposed respectively.The results of experiments show that these two models both have high fidelity.展开更多
Based on the 65nm CMOS process,a novel parallel RLC coupling interconnect analytical model is presented synthetically considering parasitical capacitive and parasitical inductive effects. Applying function approximati...Based on the 65nm CMOS process,a novel parallel RLC coupling interconnect analytical model is presented synthetically considering parasitical capacitive and parasitical inductive effects. Applying function approximation and model order-reduction to the model, we derive a closed-form and time-domain waveform for the far-end crosstalk of a victim line under ramp input transition. For various interconnect coupling sizes, the proposed RLC coupling analytical model enables the estimation of the crosstalk voltage within 2.50% error compared with Hspice simulation in a 65nm CMOS process. This model can be used in computer-aided-design of nanometer SOCs.展开更多
RLC model is used to estimate the coupling noise between interconnect wires and make some analysis through the simulation result. Based on the analysis conclusion,some algorithms are developed to adjust the rou ting ...RLC model is used to estimate the coupling noise between interconnect wires and make some analysis through the simulation result. Based on the analysis conclusion,some algorithms are developed to adjust the rou ting result with crosstalk constraint.展开更多
Liver fibrosis is the common pathological basis of all chronic liver diseases,and is the necessary stage for the progression of chronic liver disease to cirrhosis.As one of pathogenic factors,inflammation plays a pred...Liver fibrosis is the common pathological basis of all chronic liver diseases,and is the necessary stage for the progression of chronic liver disease to cirrhosis.As one of pathogenic factors,inflammation plays a predominant role in liver fibrosis via communication and interaction between inflammatory cells,cytokines,and the related signaling pathways.Damaged hepatocytes induce an increase in proinflammatory factors,thereby inducing the development of inflammation.In addition,it has been reported that inflammatory response related signaling pathway is the main signal transduction pathway for the development of liver fibrosis.The crosstalk regulatory network leads to hepatic stellate cell activation and proinflammatory cytokine production,which in turn initiate the fibrotic response.Compared with the past,the research on the pathogenesis of liver fibrosis has been greatly developed.However,the liver fibrosis mechanism is complex and many pathways involved need to be further studied.This review mainly focuses on the crosstalk regulatory network among inflammatory cells,cytokines,and the related signaling pathways in the pathogenesis of chronic inflammatory liver diseases.Moreover,we also summarize the recent studies on the mechanisms underlying liver fibrosis and clinical efforts on the targeted therapies against the fibrotic response.展开更多
Pulmonary abnormalities,dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease(IBD) more frequently than previously recognized.Emerging evidence suggests that subtle inflammation exists ...Pulmonary abnormalities,dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease(IBD) more frequently than previously recognized.Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms,and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy,with failure to isolate bacterial pathogens on repeated sputum culture,and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel.Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD,the detailed mechanisms of pulmonaryintestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities,dysfunction,or hyper-reactivity among IBD patients need further evaluation. Here,we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy.展开更多
Autophagy is a conserved intracellular degradation system that plays a dual role in cell death;thus,therapies targeting autophagy in cancer are somewhat controversial.Ferroptosis is a new form of regulated cell death ...Autophagy is a conserved intracellular degradation system that plays a dual role in cell death;thus,therapies targeting autophagy in cancer are somewhat controversial.Ferroptosis is a new form of regulated cell death featured with the iron-dependent accumulation of lethal lipid ROS.This pathway is morphologically,biochemically and genetically distinct from other forms of cell death.Accumulating studies have revealed crosstalk between autophagy and ferroptosis at the molecular level.In this review,we summarize the mechanisms of ferroptosis and autophagy,and more importantly,their roles in the drug resistance of cancer.Numerous connections between ferroptosis and autophagy have been revealed,and a strong causal relationship exists wherein one process controls the other and can be utilized as potential therapeutic targets for cancer.The elucidation of when and how to modulate their crosstalk using therapeutic strategies depends on an understanding of the fine-tuned switch between ferroptosis and autophagy,and approaches designed to manipulate the intensity of autophagy might be the key.展开更多
Hepatitis B virus(HBV) infection is a major public healthproblem worldwide. HBV is not directly cytotoxic to infected hepatocytes; the clinical outcome of infection results from complicated interactions between the vi...Hepatitis B virus(HBV) infection is a major public healthproblem worldwide. HBV is not directly cytotoxic to infected hepatocytes; the clinical outcome of infection results from complicated interactions between the virus and the host immune system. In acute HBV infection, initiation of a broad, vigorous immune response is res-ponsible for viral clearance and self-limited inflammatory liver disease. Effective and coordinated innate and adaptive immune responses are critical for viral clearance and the development of long-lasting immunity. Chronic hepatitis B patients fail to mount efficient innate and adaptive immune responses to the virus. In particular, HBV-specific cytotoxic T cells, which are crucial for HBV clearance, are hyporesponsiveness to HBV infection. Accumulating experimental evidence obtained from the development of animal and cell line models has highlighted the importance of innate immunity in the early control of HBV spread. The virus has evolved immune escape strategies, with higher HBV loads and HBV protein concentrations associated with increasing impairment of immune function. Therefore, treatment of HBV infection requires inhibition of HBV replication and protein expression to restore the suppressed host immunity. Complicated interactions exist not only between innate and adaptive responses, but also among innate immune cells and different components of adaptive responses. Improved insight into these complex interactions are important in designing new therapeutic strategies for the treatment HBV infection. In this review, we summarize the current knowledge regarding the cross-talk between the innate and adaptive immune responses and among different immunocytes in HBV infection.展开更多
<abstract>Ageing in man is associated with a decline in testosterone following changes in the hypothalamo-pituitary testicular axis. This may offset the physiologic equilibrium between oestrogen and androgen and...<abstract>Ageing in man is associated with a decline in testosterone following changes in the hypothalamo-pituitary testicular axis. This may offset the physiologic equilibrium between oestrogen and androgen and at some point when the ratio of free testosterone to oestradiol reaches a critical level, the oestrogenic gonadotropin suppressive effect predominates with decreased release of FSH and LH. Adding to this endocrinal complexity is the continued peripheral conversion to oestradiol through aromatisation. Although the androgen deficiency is not the sole cause for impotence in the elderly, there is a gradual decrease in nocturnal penile tumescence (NPT) and spontaneous morning erections with ageing. Despite the age related increase in oestrogen levels, the information on the pathophysiological role of the 'female hormone' in erectile dysfunction has been scanty. Together with our identification of oestrogen receptors within the penile cavernosum, we have delineated dysfunctional changes on male erection mediated by oestradiol. These findings parallel the recent concerns over environmental oestrogens on fertility declines in young men. Oestrogenic activity is also present in plants and thereby in human diet. These phytoestrogens are structurally and functionally similar to oestradiol and more potent than the environmental oestrogenic chemicals such as organochlorine and phenolic compounds. Thus in the light of growing concerns of possible compromising effects on sexuality by endogenous and environmental oestrogens, we are faced with the scientific need to delineate their role on the mechanism of male erectile pathway in health and disease for clinical correlates and prognostics.展开更多
Major pulmonary disorders may occur after brain injuries as ventilator-associated pneumonia, acute respiratory distress syndrome or neurogenic pulmonary edema. They are key points for the management of brain-injured p...Major pulmonary disorders may occur after brain injuries as ventilator-associated pneumonia, acute respiratory distress syndrome or neurogenic pulmonary edema. They are key points for the management of brain-injured patients because respiratory failure and mechanical ventilation seem to be a risk factor for increased mortality, poor neurological outcome and longer intensive care unit or hospital length of stay. Brain and lung strongly interact via complex pathways from the brain to the lung but also from the lung to the brain. Several hypotheses have been proposed with a particular interest for the recently described "double hit" model. Ventilator setting in brain-injured patients with lung injuries has been poorly studied and intensivists are often fearful to use some parts of protective ventilation in patients with brain injury. This review aims to describe the epidemiology and pathophysiology of lung injuries in brain-injured patients, but also the impact of different modalities of mechanical ventilation on the brain in the context of acute brain injury.展开更多
BACKGROUND Obesity is a recognized risk factor for endometrial cancer (EmCa) and other cancer types. Leptin levels are significantly increased in obese individuals. Leptin-induced signaling crosstalk [Notch, Interleuk...BACKGROUND Obesity is a recognized risk factor for endometrial cancer (EmCa) and other cancer types. Leptin levels are significantly increased in obese individuals. Leptin-induced signaling crosstalk [Notch, Interleukin-1 (IL-1) and leptin outcome, NILCO] has been associated with breast cancer progression. This complex signaling crosstalk affects cancer cell proliferation, migration, invasion, angiogenesis, apoptosis and chemoresistance. NILCO expression was previously detected in human EmCa. However, it is unknown whether leptin regulates NILCO and alters EmCa’s response to chemotherapeutics. It is hypothesized that leptin induces NILCO and increases aggressiveness and chemoresistance in EmCa cells. AIM To determine whether leptin induces NILCO molecules in EmCa affecting cell proliferation, aggressiveness and chemoresistance. METHODS Leptin’s effects on the expression of NILCO molecules [mRNAs and proteins for Notch receptors (Notch1-4), ligands (JAG1 and DLL4) and downstream effectors (survivin, Hey2), and leptin (OB-R) and IL-1 (IL-1R tI) receptors] was examined in EmCa cells (type I: Ishikawa, and HEC-1A, and type II: An3Ca and KLE) using Real-time PCR and Western blot analysis, respectively. In addition, the effects of leptin on cell cycle, proliferation and cell invasion were determined using cytometric analysis (Cellometer Vision CBA system), MTT cell proliferation and Matrigel-based invasion assays, respectively. Inhibitors of leptin (nanoparticlebound leptin peptide receptor antagonist-2, IONP-LPrA2), IL-1 (anti-IL-1R tI antibody) and Notch (siRNA interference RNA) were used to investigate NILCO’s effects on cell proliferation and invasion. Leptin’s effects on Paclitaxel cytotoxicity in EmCa cells was determined by the CCK8 and Cellometer-based Annexin V assays. RESULTS For the first time it was shown that leptin is an inducer of Notch in EmCa. Experimental data suggest that leptin induced the expression of NILCO molecules, promoted proliferation and S- phase progression, and reduced Paclitaxel cytotoxicity on EmCa cells. Leptin’s effects were higher in type II EmCa cells. The progression of this more aggressive form of the disease is associated with obesity. Remarkably, the use of the leptin signaling antagonist, IONPLPrA2, re-sensitized EmCa cells to Paclitaxel. CONCLUSION Present data suggest the notion that leptin-induced NILCO could be a link between obesity and EmCa progression and chemoresistance. Most aggressive type II EmCa cells were higher sensitive to leptin, which appears to increase proliferation, cell cycle progression, aggressiveness, and chemoresistance to Paclitaxel. Therefore, leptin and NILCO could be novel therapeutic targets for type II EmCa, which does not have targeted therapy. Overall, IONP-LPrA2 has a potential as a novel adjuvant drug to enhance the effectiveness of type II EmCa chemotherapy.展开更多
An autostereoscopic display composed of a directional backlight, an image display panel, a striped half-wave plate,and a polarized lenticular lens array is proposed. The directional backlight emitting the parallel lig...An autostereoscopic display composed of a directional backlight, an image display panel, a striped half-wave plate,and a polarized lenticular lens array is proposed. The directional backlight emitting the parallel light can redirect the cones of light to lenticular lens array and reduce the chromatic spatial-interference effect. The striped half-wave plate, located in front of the image display panel, transformed the polarization direction of the lights from the directional backlight into two mutually perpendicular directions. The polarized lenticular lens array not only can divide the light from the left and right view images to send to left and right eyes but also can reduce the crosstalk of the stereoscopic images. The proposed autostereoscopic display can produce high quality stereoscopic images without crosstalk at the optimal viewing distance.展开更多
An algorithm to resolve the coupling effect problem is proposed during the cross point assignment (CPA) stage.In the algorithm,the priority queue concept and the rip-up and reroute strategy are combined to control cro...An algorithm to resolve the coupling effect problem is proposed during the cross point assignment (CPA) stage.In the algorithm,the priority queue concept and the rip-up and reroute strategy are combined to control crosstalk noise caused by interconnect coupling capacitance.First,the nets are arranged into different priority queues according to their weighted sum of their length and criticality.Then,the CPA problem for one queue of nets is translated into a linear assignment problem.After the assignment of one queue of nets,a post-CPA checking routine is performed to check and rip up the net pairs which violate the crosstalk noise constraint and then push them into the next queue to be reassigned.The algorithm is tested by a set of bench mark examples,and the experimental results are promising...展开更多
Through-silicon-via (TSV) to TSV crosstalk noise is one of the key factors affecting the signal integrity of three- dimensional integrated circuits (3D ICs). Based on the frequency dependent equivalent electrical ...Through-silicon-via (TSV) to TSV crosstalk noise is one of the key factors affecting the signal integrity of three- dimensional integrated circuits (3D ICs). Based on the frequency dependent equivalent electrical parameters for the TSV channel, an analytical crosstalk noise model is established to capture the TSV induced crosstalk noise. The impact of various design parameters including insulation dielectric, via pitch, via height, silicon conductivity, and terminal impedance on the crosstalk noise is analyzed with the proposed model. Two approaches are proposed to alleviate the TSV noise, namely, driver sizing and via shielding, and the SPICE results show 241 rnV and 379 mV reductions in the peak noise voltage, respectively.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant Nos.12074179 and U21A_(2)0436)the Innovation Program for Quantum Science and Technology(Grant No.2021ZD0301702)+1 种基金the Natural Science Foundation of Jiangsu Province,China(Grant Nos.BE2021015-1 and BK20232002)the Natural Science Foundation of Shandong Province(Grant No.ZR2023LZH002).
文摘Performance of a scalable quantum processor critically relies on minimizing crosstalk and unwanted interactions within the system,as it is vital for parallel controlled operations on qubits.We present a protocol not only to provide information about residual coupling but also to effectively discriminate it from the influence of classical crosstalk.Our approach utilizes out-of-time-order correlators(OTOCs)as a signal of quantum crosstalk,making it applicable to various coupling forms and scalable architectures.To demonstrate the effectiveness of our protocol,we provide a theoretical analysis and simulate its implementation in coupled superconducting qubits.
基金Project supported by the Key Projects of Hunan Provincial Department of Education(Grant No.23A0133)the Natural Science Foundation of Hunan Province(Grant No.2022JJ30572)the National Natural Science Foundations of China(Grant No.62171401).
文摘Synaptic crosstalk is a prevalent phenomenon among neuronal synapses,playing a crucial role in the transmission of neural signals.Therefore,considering synaptic crosstalk behavior and investigating the dynamical behavior of discrete neural networks are highly necessary.In this paper,we propose a heterogeneous discrete neural network(HDNN)consisting of a three-dimensional KTz discrete neuron and a Chialvo discrete neuron.These two neurons are coupled mutually by two discrete memristors and the synaptic crosstalk is considered.The impact of crosstalk strength on the firing behavior of the HDNN is explored through bifurcation diagrams and Lyapunov exponents.It is observed that the HDNN exhibits different coexisting attractors under varying crosstalk strengths.Furthermore,the influence of different crosstalk strengths on the synchronized firing of the HDNN is investigated,revealing a gradual attainment of phase synchronization between the two discrete neurons as the crosstalk strength decreases.
基金the National Natural Science Foundation of China(32370248)the Jiangsu Seed Industry Revitalization Project(JBGS[2021]001)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Rice(Oryza sativa)plant architecture and grain shape,which determine grain quality and yield,are modulatedby auxin and brassinosteroid via regulation of cell elongation and proliferation.We review the signaltransduction of these hormones and the crosstalk between their signals on the regulation of rice plantarchitecture and grain shape.
文摘As develops in deep sub micron designs,the interconnect crosstalk becomes much more serious.Espe cially, the coupling inductance can not be ignored in gigahertz designs.So shield insertion is an efficient technique to reduce the inductive noise.In this paper,the characteristics of on chip mutual inductance (as well as self) for coplanar,micro stripline and stripline structures are introduced first.Then base on the coplanar interconnect structures,the effective coupling K eff model and the RLC explicit noise model are proposed respectively.The results of experiments show that these two models both have high fidelity.
文摘Based on the 65nm CMOS process,a novel parallel RLC coupling interconnect analytical model is presented synthetically considering parasitical capacitive and parasitical inductive effects. Applying function approximation and model order-reduction to the model, we derive a closed-form and time-domain waveform for the far-end crosstalk of a victim line under ramp input transition. For various interconnect coupling sizes, the proposed RLC coupling analytical model enables the estimation of the crosstalk voltage within 2.50% error compared with Hspice simulation in a 65nm CMOS process. This model can be used in computer-aided-design of nanometer SOCs.
文摘RLC model is used to estimate the coupling noise between interconnect wires and make some analysis through the simulation result. Based on the analysis conclusion,some algorithms are developed to adjust the rou ting result with crosstalk constraint.
文摘Liver fibrosis is the common pathological basis of all chronic liver diseases,and is the necessary stage for the progression of chronic liver disease to cirrhosis.As one of pathogenic factors,inflammation plays a predominant role in liver fibrosis via communication and interaction between inflammatory cells,cytokines,and the related signaling pathways.Damaged hepatocytes induce an increase in proinflammatory factors,thereby inducing the development of inflammation.In addition,it has been reported that inflammatory response related signaling pathway is the main signal transduction pathway for the development of liver fibrosis.The crosstalk regulatory network leads to hepatic stellate cell activation and proinflammatory cytokine production,which in turn initiate the fibrotic response.Compared with the past,the research on the pathogenesis of liver fibrosis has been greatly developed.However,the liver fibrosis mechanism is complex and many pathways involved need to be further studied.This review mainly focuses on the crosstalk regulatory network among inflammatory cells,cytokines,and the related signaling pathways in the pathogenesis of chronic inflammatory liver diseases.Moreover,we also summarize the recent studies on the mechanisms underlying liver fibrosis and clinical efforts on the targeted therapies against the fibrotic response.
文摘Pulmonary abnormalities,dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease(IBD) more frequently than previously recognized.Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms,and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy,with failure to isolate bacterial pathogens on repeated sputum culture,and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel.Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD,the detailed mechanisms of pulmonaryintestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities,dysfunction,or hyper-reactivity among IBD patients need further evaluation. Here,we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy.
基金supported by the National Natural Science Foundation of China (Grant No. 81602471, 81672729, 81672729, 81874380 and 81672932)Zhejiang Provincial Natural Science Foundation of China under Grants (Grant No. LY19H160055, LY19H160059)+5 种基金by Zheng Shu Medical Elite Scholarship Fundby grant from sub-project of China National Program on Key Basic Research Project (973 Program) (Grant No. 2014CB744505)Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars (Grant No. LR18H160001)Zhejiang Province Medical Science and Technology Project (Grant No. 2017RC007)Talent Project of Zhejiang Association for Science and Technology (Grant No. 2017YCGC002)Zhejiang Province Science and Technology Project of TCM (Grant No. 2019ZZ016)
文摘Autophagy is a conserved intracellular degradation system that plays a dual role in cell death;thus,therapies targeting autophagy in cancer are somewhat controversial.Ferroptosis is a new form of regulated cell death featured with the iron-dependent accumulation of lethal lipid ROS.This pathway is morphologically,biochemically and genetically distinct from other forms of cell death.Accumulating studies have revealed crosstalk between autophagy and ferroptosis at the molecular level.In this review,we summarize the mechanisms of ferroptosis and autophagy,and more importantly,their roles in the drug resistance of cancer.Numerous connections between ferroptosis and autophagy have been revealed,and a strong causal relationship exists wherein one process controls the other and can be utilized as potential therapeutic targets for cancer.The elucidation of when and how to modulate their crosstalk using therapeutic strategies depends on an understanding of the fine-tuned switch between ferroptosis and autophagy,and approaches designed to manipulate the intensity of autophagy might be the key.
基金Supported by Grants of Yantai Science and Technology Plan Project,No.2012116
文摘Hepatitis B virus(HBV) infection is a major public healthproblem worldwide. HBV is not directly cytotoxic to infected hepatocytes; the clinical outcome of infection results from complicated interactions between the virus and the host immune system. In acute HBV infection, initiation of a broad, vigorous immune response is res-ponsible for viral clearance and self-limited inflammatory liver disease. Effective and coordinated innate and adaptive immune responses are critical for viral clearance and the development of long-lasting immunity. Chronic hepatitis B patients fail to mount efficient innate and adaptive immune responses to the virus. In particular, HBV-specific cytotoxic T cells, which are crucial for HBV clearance, are hyporesponsiveness to HBV infection. Accumulating experimental evidence obtained from the development of animal and cell line models has highlighted the importance of innate immunity in the early control of HBV spread. The virus has evolved immune escape strategies, with higher HBV loads and HBV protein concentrations associated with increasing impairment of immune function. Therefore, treatment of HBV infection requires inhibition of HBV replication and protein expression to restore the suppressed host immunity. Complicated interactions exist not only between innate and adaptive responses, but also among innate immune cells and different components of adaptive responses. Improved insight into these complex interactions are important in designing new therapeutic strategies for the treatment HBV infection. In this review, we summarize the current knowledge regarding the cross-talk between the innate and adaptive immune responses and among different immunocytes in HBV infection.
文摘<abstract>Ageing in man is associated with a decline in testosterone following changes in the hypothalamo-pituitary testicular axis. This may offset the physiologic equilibrium between oestrogen and androgen and at some point when the ratio of free testosterone to oestradiol reaches a critical level, the oestrogenic gonadotropin suppressive effect predominates with decreased release of FSH and LH. Adding to this endocrinal complexity is the continued peripheral conversion to oestradiol through aromatisation. Although the androgen deficiency is not the sole cause for impotence in the elderly, there is a gradual decrease in nocturnal penile tumescence (NPT) and spontaneous morning erections with ageing. Despite the age related increase in oestrogen levels, the information on the pathophysiological role of the 'female hormone' in erectile dysfunction has been scanty. Together with our identification of oestrogen receptors within the penile cavernosum, we have delineated dysfunctional changes on male erection mediated by oestradiol. These findings parallel the recent concerns over environmental oestrogens on fertility declines in young men. Oestrogenic activity is also present in plants and thereby in human diet. These phytoestrogens are structurally and functionally similar to oestradiol and more potent than the environmental oestrogenic chemicals such as organochlorine and phenolic compounds. Thus in the light of growing concerns of possible compromising effects on sexuality by endogenous and environmental oestrogens, we are faced with the scientific need to delineate their role on the mechanism of male erectile pathway in health and disease for clinical correlates and prognostics.
文摘Major pulmonary disorders may occur after brain injuries as ventilator-associated pneumonia, acute respiratory distress syndrome or neurogenic pulmonary edema. They are key points for the management of brain-injured patients because respiratory failure and mechanical ventilation seem to be a risk factor for increased mortality, poor neurological outcome and longer intensive care unit or hospital length of stay. Brain and lung strongly interact via complex pathways from the brain to the lung but also from the lung to the brain. Several hypotheses have been proposed with a particular interest for the recently described "double hit" model. Ventilator setting in brain-injured patients with lung injuries has been poorly studied and intensivists are often fearful to use some parts of protective ventilation in patients with brain injury. This review aims to describe the epidemiology and pathophysiology of lung injuries in brain-injured patients, but also the impact of different modalities of mechanical ventilation on the brain in the context of acute brain injury.
基金Supported by the National Cancer Institute at the National Institutes of Health,No.S21 MD000101,No.5G12 MD0076021,No.G12RR026250-03,No.NIH RR030341C06,No.RR18386 to Morehouse School of Medicinethe National Institute of General Medical Sciences,National Institutes of Health,No.5T32HL103104-04 to DDB
文摘BACKGROUND Obesity is a recognized risk factor for endometrial cancer (EmCa) and other cancer types. Leptin levels are significantly increased in obese individuals. Leptin-induced signaling crosstalk [Notch, Interleukin-1 (IL-1) and leptin outcome, NILCO] has been associated with breast cancer progression. This complex signaling crosstalk affects cancer cell proliferation, migration, invasion, angiogenesis, apoptosis and chemoresistance. NILCO expression was previously detected in human EmCa. However, it is unknown whether leptin regulates NILCO and alters EmCa’s response to chemotherapeutics. It is hypothesized that leptin induces NILCO and increases aggressiveness and chemoresistance in EmCa cells. AIM To determine whether leptin induces NILCO molecules in EmCa affecting cell proliferation, aggressiveness and chemoresistance. METHODS Leptin’s effects on the expression of NILCO molecules [mRNAs and proteins for Notch receptors (Notch1-4), ligands (JAG1 and DLL4) and downstream effectors (survivin, Hey2), and leptin (OB-R) and IL-1 (IL-1R tI) receptors] was examined in EmCa cells (type I: Ishikawa, and HEC-1A, and type II: An3Ca and KLE) using Real-time PCR and Western blot analysis, respectively. In addition, the effects of leptin on cell cycle, proliferation and cell invasion were determined using cytometric analysis (Cellometer Vision CBA system), MTT cell proliferation and Matrigel-based invasion assays, respectively. Inhibitors of leptin (nanoparticlebound leptin peptide receptor antagonist-2, IONP-LPrA2), IL-1 (anti-IL-1R tI antibody) and Notch (siRNA interference RNA) were used to investigate NILCO’s effects on cell proliferation and invasion. Leptin’s effects on Paclitaxel cytotoxicity in EmCa cells was determined by the CCK8 and Cellometer-based Annexin V assays. RESULTS For the first time it was shown that leptin is an inducer of Notch in EmCa. Experimental data suggest that leptin induced the expression of NILCO molecules, promoted proliferation and S- phase progression, and reduced Paclitaxel cytotoxicity on EmCa cells. Leptin’s effects were higher in type II EmCa cells. The progression of this more aggressive form of the disease is associated with obesity. Remarkably, the use of the leptin signaling antagonist, IONPLPrA2, re-sensitized EmCa cells to Paclitaxel. CONCLUSION Present data suggest the notion that leptin-induced NILCO could be a link between obesity and EmCa progression and chemoresistance. Most aggressive type II EmCa cells were higher sensitive to leptin, which appears to increase proliferation, cell cycle progression, aggressiveness, and chemoresistance to Paclitaxel. Therefore, leptin and NILCO could be novel therapeutic targets for type II EmCa, which does not have targeted therapy. Overall, IONP-LPrA2 has a potential as a novel adjuvant drug to enhance the effectiveness of type II EmCa chemotherapy.
基金Project supported by the National High Technology Research and Development Program of China(Grant No.2012AA03A301)the National Natural Science Foundation of China(Grant No.60932007)+1 种基金the Postdoctoral Science Programs Foundation of the Ministry of Education of China(Grant No.0110032110029)the Key Projects in the Tianjin Science & Technology Pillar Program,China(Grant No.11ZCKFGX02000)
文摘An autostereoscopic display composed of a directional backlight, an image display panel, a striped half-wave plate,and a polarized lenticular lens array is proposed. The directional backlight emitting the parallel light can redirect the cones of light to lenticular lens array and reduce the chromatic spatial-interference effect. The striped half-wave plate, located in front of the image display panel, transformed the polarization direction of the lights from the directional backlight into two mutually perpendicular directions. The polarized lenticular lens array not only can divide the light from the left and right view images to send to left and right eyes but also can reduce the crosstalk of the stereoscopic images. The proposed autostereoscopic display can produce high quality stereoscopic images without crosstalk at the optimal viewing distance.
文摘An algorithm to resolve the coupling effect problem is proposed during the cross point assignment (CPA) stage.In the algorithm,the priority queue concept and the rip-up and reroute strategy are combined to control crosstalk noise caused by interconnect coupling capacitance.First,the nets are arranged into different priority queues according to their weighted sum of their length and criticality.Then,the CPA problem for one queue of nets is translated into a linear assignment problem.After the assignment of one queue of nets,a post-CPA checking routine is performed to check and rip up the net pairs which violate the crosstalk noise constraint and then push them into the next queue to be reassigned.The algorithm is tested by a set of bench mark examples,and the experimental results are promising...
基金Project supported by the National Natural Science Foundation of China(Grant Nos.61131001,61322405,61204044,61376039,and 61334003)
文摘Through-silicon-via (TSV) to TSV crosstalk noise is one of the key factors affecting the signal integrity of three- dimensional integrated circuits (3D ICs). Based on the frequency dependent equivalent electrical parameters for the TSV channel, an analytical crosstalk noise model is established to capture the TSV induced crosstalk noise. The impact of various design parameters including insulation dielectric, via pitch, via height, silicon conductivity, and terminal impedance on the crosstalk noise is analyzed with the proposed model. Two approaches are proposed to alleviate the TSV noise, namely, driver sizing and via shielding, and the SPICE results show 241 rnV and 379 mV reductions in the peak noise voltage, respectively.