Central role of Yes-associated protein and WW-domain-containing transcriptional co-activator with PDZ-binding motif in pancreatic cancer development

Pancreatic ductal adenocarcinoma(PDAC) remains a deadly disease with no efficacious treatment options. PDAC incidence is projected to increase, which may be caused at least partially by the obesity epidemic. Significantly enhanced efforts to prevent or intercept this cancer are clearly warranted. Oncogenic KRAS mutations are recognized initiating events in PDAC development, however, they are not entirely sufficient for the development of fully invasive PDAC.Additional genetic alterations and/or environmental, nutritional, and metabolic signals, as present in obesity, type-2 diabetes mellitus, and inflammation, are required for full PDAC formation. We hypothesize that oncogenic KRAS increases the intensity and duration of the growth-promoting signaling network.Recent exciting studies from different laboratories indicate that the activity of the transcriptional co-activators Yes-associated protein(YAP) and WW-domaincontaining transcriptional co-activator with PDZ-binding motif(TAZ) play a critical role in the promotion and maintenance of PDAC operating as key downstream target of KRAS signaling. While initially thought to be primarily an effector of the tumor-suppressive Hippo pathway, more recent studies revealed that YAP/TAZ subcellular localization and co-transcriptional activity is regulated by multiple upstream signals. Overall, YAP has emerged as a central node of transcriptional convergence in growth-promoting signaling in PDAC cells. Indeed, YAP expression is an independent unfavorable prognostic marker for overall survival of PDAC. In what follows, we will review studies implicating YAP/TAZ in pancreatic cancer development and consider different approaches to target these transcriptional regulators.

Statistical Analysis on Gender Difference in Neural Activity for Spatial Ability Tasks

Gender differences are investigated from the viewpoint of cognitive neuroscience in the domain of spatial ability. Five task types of geometric problems are used for the collection of task-evoked fMRI data. Although there was no gender-difference in task performance, we found gender differences in neural activity. Some of the important gender differences that we found are 1) that there are far more joint neuro-activations among the brain regions, co-activations or reverse-activations, in males than in females, 2) that the two types of joint activations were nearly half and half in females while it was mostly co-activations in males, 3) that males tend to have more co-activations in the left hemisphere than expected while females tend to have more between-hemisphere co-activations than expected, and 4) that the left-right pairs of BA's are more highly associated than average for males while they are far less associated than average for females.

吡格列酮对大鼠缺血/再灌注心肌过氧化物酶体增殖物受体γ辅激活因子lα表达的影响

目的观察吡格列酮对大鼠缺血/再灌注损伤心肌过氧化物酶体增殖物受体γ辅激活因子lα(PGC-lα)表达的影响。方法 24只SD大鼠随机分为4组(n=6):缺血/再灌注组、吡格列酮5 mg/(kg·d)组、吡格列酮10 mg/(kg·d)组、吡格列酮10 mg/(kg·d)+过氧化物酶体增殖物激活受体γ(PPARγ)特异性阻断剂GW9662组,利用在体结扎左前降支的方法建立缺血/再灌注损伤模型,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL法)检测心肌细胞凋亡,RT-PCR方法检测心肌组织PGC-lαmRNA的变化,Western blot检测心肌组织PGC-lα蛋白的变化。结果 TUNEL法显示吡格列酮抑制缺血/再灌注心肌细胞凋亡[(21.4±8.8)%、(17.3±8.7)%、(40.1±12.3)%,P<0.05)],吡格列酮上调PGC-lα表达(P<0.05),GW9662逆转吡格列酮对凋亡细胞的抑制作用(P<0.05),抑制吡格列酮促进PGC-lα表达上调的作用(P<0.05)。结论吡格列酮抑制缺血/再灌注损伤诱导的心肌细胞凋亡,吡格列酮促进PGC-lα上调,这两种作用是由PPARγ介导的。

Effect of methane co-feeding on the selectivity of ethylene produced from oxidative dehydrogenation of ethane with CO_2 over a Ni-La/SiO_2 catalyst

A Ni-La/SiO2 catalyst was prepared through the incipient wetness impregnation method and tested in the oxidative dehydrogenation of ethane （ODHE） with CO2. The fresh and used catalysts were characterized by XRD and SEM techniques. The Ni-La/SiO2 catalyst exhibited catalytic activity for the oxidative dehydrogenation of ethane, but with low ethylene selectivity in the absence of methane. The selectivity to ethylene increased with increasing molar ratio of methane in the feed. The carbon deposited on the catalyst surface in the sole ODHE with CO2 was mainly inert carbon, while much more filamentous carbon was formed in the presence of methane. The filamentous carbon was easy to be removed by CO2, which might play a role in improving the conversion of ethane to ethylene. The introduction of methane might affect the equilibrium of the CO2 reforming of ethane and the ODHE with CO2. As a consequence, the synthesis gas produced from CO2 reforming of methane partly inhibited the reaction of ethane and promoted the ODHE with CO2, thus increasing the selectivity of ethylene.

Neuromuscular interactions around the knee in children, adults and elderly

Although injury and neuromuscular activation patterns may be common for all individuals, there are certain factors which differentiate neuromuscular activity responses between children, adults and elderly. The purpose of this study is to review recent evidence on age differences in neural activation and muscle balances around the knee when performing single joint movements. Particularly, current evidence indicates that there are some interesting similarities in the neuromuscular mechanisms by which children or the elderly differ compared with adults. Both children and elderly display a lower absolute muscle strength capacity than adults which cannot fully be explained by differences in muscle mass. Quadriceps activation failure is a common symptom ofall knee injuries, irrespective of age but it is likely that its effect is more evident in children or adults. While one might expect that antagonist co-activation would differ between age categories, it appears that this is not the case. Although hamstring: quadriceps ratio levels are altered after knee injury, it is not clear whether this is an age specific response. Finally, evidence suggests that both children and the elderly display less stiffness of the quadriceps muscle-tendon unit than adults which affects their knee joint function.

Cortico–subcortical spatiotemporal dynamics in Parkinson’s disease can be modulated by transcranial alternating current stimulation

Objective:We investigated changes in cortico–subcortical spatiotemporal dynamics to explore the treatment mechanisms oftranscranial alternating current stimulation(tACS)in patientswith Parkinson’s disease(PD).Methods:Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from 20 patients with PD and 20 normal controls(NC).Each patient with PD received successivemultidisciplinary intensive rehabilitation treatment and tACStreatment over a one-year interval.Individual functional brain network mapping and co-activation pattern(CAP)analysis were performed to characterize cortico–subcortical dynamics.Results:The same tACS electrode placement stimulated different proportions of functional brain networks across the participants.CAP analysis revealed that the visual network,attentional network,and default mode network co-activated with the thalamus,accumbens,and amygdala,respectively.The pattern characterized by thede-activation of the visual network and the activation of the thalamus showed a significantly low amplitude in the patients with PD than inNCs,and this amplitude increased after tACS treatment.Furthermore,the co-occurrence of cortico–subcortical CAPs was significantly higherin patients with PD than in NCs and decreased after tACS treatment.Conclusions:This study investigated cortico–subcortical spatiotemporaldynamics in patients with PD and further revealed the tACS treatmentmechanism.These findings contribute to understanding cortico–subcortical dynamics and exploring noninvasive neuromodulationtargets of cortico–subcortical circuits in brain diseases,such as PD,Alzheimer’s disease,and depression.

Facile Self-templating Melting Route Preparation of Biomass-derived Hierarchical Porous Carbon for Advanced Supercapacitors

Biomass-derived porous carbons show great potential as electrode materials for supercapacitors due to the environmental friendliness. However, most of the carbonaceous electrode materials suffer from low specific capacitance and rate capacity because of the poor porosity. Here, we reported a simple and effective approach to prepare micro/nano-hierarchical structured carbon materials derived from rice husk by NaOH-KOH molten salt co-activation. The as-prepared activated carbons exhibit high porosity and suitable pore size distributions for more electrolyte ion adsorption, which are all beneficial for achieving remarkable electrochemical performances, such as high specific capacitance（194.6 F/g）, excellent rate capability（retention of 85.9%） and outstanding cycling stability. Thus, the above biomass-derived carbon materials with high porosity and micro/nano structures obtained by co-activation method offered a new insight into novel electrode material for the use in energy storage systems with high energy density and excellent rate performance.

Psoralen inhibits hepatitis B viral replication by down-regulating the host transcriptional machinery of viral promoters

The hepatitis B virus(HBV) is a global public health challenge due to its highly contagious nature. It is estimated that almost 300 million people live with chronic HBV infection annually. Although nucleoside analogs markedly reduce the risk of liver disease progression, the analogs do not fully eradicate the virus. As such, new treatment options and drugs are urgently needed. Psoralen is a nourishing monomer of Chinese herb and is known to inhibit virus replication and inactivate viruses. In this study, we evaluated the potential of psoralen as an anti-HBV agent.Quantitative PCR and Southern blot analysis revealed that psoralen inhibited HBV replication in Hep G2.2.15 cells in a concentration-dependent manner. Moreover, psoralen was also active against the 3TC/ETV-dual-resistant HBV mutant. Further investigations revealed that psoralen suppressed both HBV RNA transcription and core protein expression. The transcription factor FOXO1, a known target for PGC1α co-activation, binds to HBV precore/core promoter enhancer II region and activates HBV RNA transcription. Co-immunoprecipitation showed that psoralen suppressed the expression of FOXO1, thereby decreasing the binding of FOXO1 co-activator PGC1αto the HBV promoter. Overall, our results demonstrate that psoralen suppresses HBV RNA transcription by downregulating the expression of FOXO1 resulting in a reduction of HBV replication.

Transcriptional activators and activation mechanisms

Transcriptional activators are required to turn on the expression of genes in a eukaryotic cell.Activators bound to the enhancer can facilitate either the recruitment of RNA polymerase II to the promoter or its elongation.This article examines a few selected issues in understanding activator functions and activation mechanisms.

Stress-Induced Uphill Diffusion with Interfacial Contact Loss in Solid-State Electrodes

We simulate the mechanical-chemical coupling during delithiation and relaxation of a cathode in a solid-state lithium-ion battery.Contact loss at the interface between the active particle and the solid electrolyte is considered.Uphill diffusion is observed during delithiation and relaxation.This phenomenon is explained by analyzing the total chemical potential and its two components.Contact loss at the interface greatly influences the stress and stress gradient in the active particle.As delithiation continues,the stress and stress gradient grow considerably,and the mechanical part of the total chemical potential becomes dominant over the chemical part of it.In the latter stage of delithiation,the influence of the incomplete interfacial constraint on the stress becomes dominant,while the effect of the concentration gradient becomes negligible.After relaxation,the concentration and stress gradients increase in a particle with contact loss.The influence of the degree of contact loss on the mechanical-chemical coupling is investigated.The overall tensile stress in the active particle increases with decreasing contact loss,causing a sharp decrease in local concentration.We also check the effect of the elastic modulus of the solid electrolyte on the coupling of the active material.A rigid solid electrolyte with a higher elastic modulus more strongly restricts the active particle,leading to a higher tensile stress,a larger stress gradient,and a greater concentration gradient.