Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, is overexpressed and activated in many cancer types. FAK regulates diverse cellular processes, including growth factor signaling, cell ...cycle progression, cell survival, cell motility, angiogenesis, and the establishment of immunosuppressive tumor microenvironments through kinase-dependent and kinase-independent scaffolding functions in the cytoplasm and nucleus. Mounting evidence has indicated that targeting FAK, either alone or in combination with other agents, may represent a promising therapeutic strategy for various cancers. In this review, we summarize the mechanisms underlying FAK-mediated signaling networks during tumor development. We also summarize the recent progress of FAK-targeted small-molecule compounds for anticancer activity from preclinical and clinical evidence.
Coronavirus infectious disease 2019 (COVID-19) has had a great impact on global health, but with relatively few confirmed cases in Taiwan. People in Taiwan showed excellent cooperation with the ...government for disease prevention and faced social and behavioral changes during this period. This study aimed to investigate people's knowledge of COVID-19, attitudes and practices regarding vaccinations for influenza, pneumococcus and COVID-19.
We conducted a community-based, cross-sectional questionnaire survey from September 2020 to October 2020 among adults in northern Taiwan. The four-part questionnaire included questions on sociodemographic characteristics, knowledge, attitude, and practice toward COVID-19.
Among a total of 410 respondents, 58.5% were categorized as having "good knowledge" responding to COVID-19. Among the total respondents, 86.6% were willing to receive influenza or pneumococcal vaccines, and 76% of them acted to receive COVID-19 immunization once the vaccine became available. Compared with the respondents with poor knowledge of COVID-19, those with good knowledge had a more positive attitude toward receiving influenza or pneumococcal immunization (OR 3.26, 95% CI = 1.74-6.12).
Participants with good knowledge of COVID-19 had greater intent to receive immunization for influenza or pneumococcal vaccine. The promotion of correct knowledge of both COVID-19 and immunization preparations is necessary.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mitigating power distribution network (PDN) noise is one of the main efforts for power integrity (PI) design in high-speed or mixed-signal circuits. Possible solutions, which are based on decoupling ...or isolation concept, for suppressing PDN noise on package or printed circuit board (PCB) levels are reviewed in this paper. Keeping the PDN impedance very low in a wide frequency range, except at dc, by employing a shunt capacitors, which can be in-chip, package, or PCB levels, is the first priority way for PI design. The decoupling techniques including the planes structure, surface-mounted technology decoupling capacitors, and embedded capacitors will be discussed. The isolation approach that keeps part of the PDN at high impedance is another way to reduce the PDN noise propagation. Besides the typical isolation approaches such as the etched slots and filter, the new isolation concept using electromagnetic bandgap structures will also be discussed.
An increasing number of enzymes involved in serine biosynthesis have been identified and correlated with malignant evolution in various types of cancer. Here we showed that the overexpression of ...phosphoserine aminotransferase 1 (PSAT1) is widely found in lung cancer tissues compared with nontumor tissues and predicts a poorer prognosis in patients with lung adenocarcinoma. PSAT1 expression was examined in a tissue microarray by immunohistochemistry. The data show that the knockdown of PSAT1 dramatically inhibits the in vitro and in vivo metastatic potential of highly metastatic lung cancer cells; conversely, the enforced expression of exogenous PSAT1 predominantly enhances the metastatic potential of lung cancer cells. Importantly, manipulating PSAT1 expression regulates the in vivo tumor metastatic abilities in lung cancer cells. Adjusting the glucose and glutamine concentrations did not alter the PSAT1-driven cell invasion properties, indicating that this process might not rely on the activation of its enzymatic function. RNA microarray analysis of transcriptional profiling from PSAT1 alternation in CL1-5 and CL1-0 cells demonstrated that interferon regulatory factor 1 (IRF1) acts as a crucial regulator of PSAT1-induced gene expression upon metastatic progression. Decreasing the IRF1-IFIH1 axis compromised the PSAT1-prompted transcriptional reprogramming in cancer cells. Our results identify PSAT1 as a key regulator by a novel PSAT1/IRF1 axis in lung cancer progression, which may serve as a potential biomarker and therapeutic target for the treatment of lung cancer patients.
Parkinson’s disease is characterized by both hypokinetic and hyperkinetic symptoms. While increased subthalamic burst discharges have a direct causal relationship with the hypokinetic manifestations ...(e.g., rigidity and bradykinesia), the origin of the hyperkinetic symptoms (e.g., resting tremor and propulsive gait) has remained obscure. Neuronal burst discharges are presumed to be autonomous or less responsive to synaptic input, thereby interrupting the information flow. We, however, demonstrate that subthalamic burst discharges are dependent on cortical glutamatergic synaptic input, which is enhanced by A-type K+ channel inhibition. Excessive top-down-triggered subthalamic burst discharges then drive highly correlative activities bottom-up in the motor cortices and skeletal muscles. This leads to hyperkinetic behaviors such as tremors, which are effectively ameliorated by inhibition of cortico-subthalamic AMPAergic synaptic transmission. We conclude that subthalamic burst discharges play an imperative role in cortico-subcortical information relay, and they critically contribute to the pathogenesis of both hypokinetic and hyperkinetic parkinsonian symptoms.
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•A-type K+ channels prominently modulate cortico-subthalamic synaptic transmission•Cortico-subthalamic glutamatergic input triggers burst firing in the subthalamic nucleus•Exaggerated bursts induce coherent oscillations in the motor cortex and skeletal muscles•Erroneous re-entrant information relay leads to parkinsonian hyperkinetic behaviors
The origin of parkinsonian tremors remains obscure. In opposition to the conventional view that neuronal burst activities are autonomous, Huang et al. show that subthalamic burst discharges are dependent on input from the motor cortex, causing erroneous re-entrant information relays from cortico-subthalamic to pallido-thalamocortical loops and thus parkinsonian tremors.
The air exchange rate (AER), defined as the number of times the air is fully replaced per hour in an indoor space, is an important parameter affecting indoor air quality (IAQ). Hospital operation ...rooms (ORs), one of the indoor environments with relatively high health risks, should maintain high AERs to quickly remove surgical smoke during surgery. This study aimed to investigate the characteristics and transmission of pollutants in ORs through on-site measurements and numerical simulations. To determine actual AER (AERactual), both exponential decay and concentration variations, resulting in a more precise representation of indoor air pollutant residence time, were considered. Our results revealed that gaseous pollutants exhibited lower AERactual values compared to particulate pollutants due to their higher diffusibility. Notably, the AERactual of total volatile organic compounds (TVOC) was found to be greater than that of carbon dioxide (CO2) due to the higher reactivity of TVOC. Furthermore, this study also investigated the characteristics of surgical smoke particles and observed variations in emission factors (EF) depending on the surgical procedure, ranging from approximately 1010 to 1011 particles per minute. Moreover, coarse particles (>2.5 μm) were primarily influenced by drag forces, resulting in lower AERactual values. Additionally, the AERactual of ultrafine particles (UFPs) was examined, revealing that smaller particles exhibited lower AERactual values, potentially due to stronger Brownian motion. By combining measurement and simulation analysis, the spatial distribution of lung deposited surface area (LDSA) concentrations could be evaluated, providing accurate exposure concentrations for health risk assessments.
•The actual air exchange rate (AER) was evaluated using the pollutant decay rate.•Actual AER was significantly lower than the nominal AER in hospital operating rooms.•Identified the emission factors of ultrafine particles during surgery.•Compared actual AERs of different particle sizes.•Mapped spatial distribution of lung deposited surface area (LDSA).
Based on the ground surface perturbation concept, a novel stopband-enhanced electromagnetic-bandgap (EBG) structure has been proposed to suppress the power/ground noise on a three-layer package. This ...structure consists of a coplanar periodic pattern on the top layer, a ground plane on the third layer, and a ground surface perturbation lattice on the second layer with eight vias connecting to the ground plane. By designing the dimension and via numbers, the ground surface perturbation lattice can significantly enhance the stopband bandwidth. A generic 1-D circuit model is proposed for the three-layer EBG structure. The reason why the proposed structure can possess wider stopband will be explained. Several test samples are fabricated. The agreement of the stopband between the circuit model and measured results are good.
Peptidyl-prolyl
isomerase NIMA-interacting 1 (Pin1) specifically binds and isomerizes the phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif, which leads to changes in protein conformation ...and function. Pin1 is widely overexpressed in cancers and plays an important role in tumorigenesis. Mounting evidence has revealed that targeting Pin1 is a potential therapeutic approach for various cancers by inhibiting cell proliferation, reducing metastasis, and maintaining genome stability. In this review, we summarize the underlying mechanisms of Pin1-mediated upregulation of oncogenes and downregulation of tumor suppressors in cancer development. Furthermore, we also discuss the multiple roles of Pin1 in cancer hallmarks and examine Pin1 as a desirable pharmaceutical target for cancer therapy. We also summarize the recent progress of Pin1-targeted small-molecule compounds for anticancer activity.
Parkinson's disease (PD), or paralysis agitans, is a common neurodegenerative disease characterized by dopaminergic deprivation in the basal ganglia because of neuronal loss in the substantia nigra ...pars compacta. Clinically, PD apparently involves both hypokinetic (e.g. akinetic rigidity) and hyperkinetic (e.g. tremor/propulsion) symptoms. The symptomatic pathogenesis, however, has remained elusive. The recent success of deep brain stimulation (DBS) therapy applied to the subthalamic nucleus (STN) or the globus pallidus pars internus indicates that there are essential electrophysiological abnormalities in PD. Consistently, dopamine-deprived STN shows excessive burst discharges. This proves to be a central pathophysiological element causally linked to the locomotor deficits in PD, as maneuvers (such as DBS of different polarities) decreasing and increasing STN burst discharges would decrease and increase the locomotor deficits, respectively. STN bursts are not so autonomous but show a "relay" feature, requiring glutamatergic synaptic inputs from the motor cortex (MC) to develop. In PD, there is an increase in overall MC activities and the corticosubthalamic input is enhanced and contributory to excessive burst discharges in STN. The increase in MC activities may be relevant to the enhanced beta power in local field potentials (LFP) as well as the deranged motor programming at the cortical level in PD. Moreover, MC could not only drive erroneous STN bursts, but also be driven by STN discharges at specific LFP frequencies (~ 4 to 6 Hz) to produce coherent tremulous muscle contractions. In essence, PD may be viewed as a disorder with deranged rhythms in the cortico-subcortical re-entrant loops, manifestly including STN, the major component of the oscillating core, and MC, the origin of the final common descending motor pathways. The configurations of the deranged rhythms may play a determinant role in the symptomatic pathogenesis of PD, and provide insight into the mechanism underlying normal motor control. Therapeutic brain stimulation for PD and relevant disorders should be adaptively exercised with in-depth pathophysiological considerations for each individual patient, and aim at a final normalization of cortical discharge patterns for the best ameliorating effect on the locomotor and even non-motor symptoms.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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