PAK in Alzheimer disease, Huntington disease and X-linked mental retardation.

Developmental cognitive deficits including X-linked mental retardation (XLMR) can be caused by mutations in P21-activated kinase 3 (PAK3) that disrupt actin dynamics in dendritic spines. Neurodegenerative diseases such as Alzheimer disease (AD), where both PAK1 and PAK3 are dysregulated, may share final common pathways with XLMR. Independent of familial mutation, cognitive deficits emerging with aging, notably AD, begin after decades of normal function. This prolonged prodromal period involves the buildup of amyloid-β (Aβ) extracellular plaques and intraneuronal neurofibrillary tangles (NFT). Subsequently region dependent deficits in synapses, dendritic spines and cognition coincide with dysregulation in PAK1 and PAK. Specifically proximal to decline, cytoplasmic levels of actin-regulating Rho GTPase and PAK1 kinase are decreased in moderate to severe AD, while aberrant activation and translocation of PAK1 appears around the onset of cognitive deficits. Downstream to PAK1, LIM kinase inactivates cofilin, contributing to cofilin pathology, while the activation of Rho-dependent kinase ROCK increases Aβ production. Aβ activation of fyn disrupts neuronal PAK1 and ROCK-mediated signaling, resulting in synaptic deficits. Reductions in PAK1 by the anti-amyloid compound curcumin suppress synaptotoxicity. Similarly other neurological disorders, including Huntington disease (HD) show dysregulation of PAKs. PAK1 modulates mutant huntingtin toxicity by enhancing huntingtin aggregation, and inhibition of PAK activity protects HD as well as fragile X syndrome (FXS) symptoms. Since PAK plays critical roles in learning and memory and is disrupted in many cognitive disorders, targeting PAK signaling in AD, HD and XLMR may be a novel common therapeutic target for AD, HD and XLMR

Understanding Client Reactions in Online Mental Health Counseling

Communication success relies heavily on reading participants' reactions. Such feedback is especially important for mental health counselors, who must carefully consider the client's progress and adjust their approach accordingly. However, previous NLP research on counseling has mainly focused on studying counselors' intervention strategies rather than their clients' reactions to the intervention. This work aims to fill this gap by developing a theoretically grounded annotation framework that encompasses counselors' strategies and client reaction behaviors. The framework has been tested against a large-scale, high-quality text-based counseling dataset we collected over the past two years from an online welfare counseling platform. Our study shows how clients react to counselors' strategies, how such reactions affect the final counseling outcomes, and how counselors can adjust their strategies in response to these reactions. We also demonstrate that this study can help counselors automatically predict their clients' states.Comment: Accept to ACL 2023, oral. For code and data, see https://github.com/dll-wu/Client-Reac

PsyBench: a balanced and in-depth Psychological Chinese Evaluation Benchmark for Foundation Models

As Large Language Models (LLMs) are becoming prevalent in various fields, there is an urgent need for improved NLP benchmarks that encompass all the necessary knowledge of individual discipline. Many contemporary benchmarks for foundational models emphasize a broad range of subjects but often fall short in presenting all the critical subjects and encompassing necessary professional knowledge of them. This shortfall has led to skewed results, given that LLMs exhibit varying performance across different subjects and knowledge areas. To address this issue, we present psybench, the first comprehensive Chinese evaluation suite that covers all the necessary knowledge required for graduate entrance exams. psybench offers a deep evaluation of a model's strengths and weaknesses in psychology through multiple-choice questions. Our findings show significant differences in performance across different sections of a subject, highlighting the risk of skewed results when the knowledge in test sets is not balanced. Notably, only the ChatGPT model reaches an average accuracy above $70\%$, indicating that there is still plenty of room for improvement. We expect that psybench will help to conduct thorough evaluations of base models' strengths and weaknesses and assist in practical application in the field of psychology

Down-regulation of Toll-like receptor 4 gene expression by short interfering RNA attenuates bone cancer pain in a rat model

<p>Abstract</p> <p>Background</p> <p>This study demonstrates a critical role in CNS innate immunity of the microglial Toll-like receptor 4 (TLR4) in the induction and maintenance of behavioral hypersensitivity in a rat model of bone cancer pain with the technique of RNA interference (RNAi). We hypothesized that after intramedullary injection of Walker 256 cells (a breast cancer cell line) into the tibia, CNS neuroimmune activation and subsequent cytokine expression are triggered by the stimulation of microglial membrane-bound TLR4.</p> <p>Results</p> <p>We assessed tactile allodynia and spontaneous pain in female Sprague-Dawley (SD) rats after intramedullary injection of Walker 256 cells into the tibia. In a complementary study, TLR4 small interfering RNA(siRNA) was administered intrathecally to bone cancer pain rats to reduce the expression of spinal TLR4. The bone cancer pain rats treated with TLR4 siRNA displayed significantly attenuated behavioral hypersensitivity and decreased expression of spinal microglial markers and proinflammatory cytokines compared with controls. Only intrathecal injection of TRL4 siRNA at post-inoculation day 4 could prevent initial development of bone cancer pain; intrathecal injection of TRL4 siRNA at post-inoculation day 9 could attenuate, but not completely block, well-established bone cancer pain.</p> <p>Conclusions</p> <p>TLR4 might be the main mediator in the induction of bone cancer pain. Further study of this early, specific, and innate CNS/microglial response, and how it leads to sustained glial/neuronal hypersensitivity, might lead to new therapies for the prevention and treatment of bone cancer pain syndromes.</p

Growth mechanism of carbon nanotubes from Co-W-C alloy catalyst revealed by atmospheric environmental transmission electron microscopy

High???melting point alloy catalysts have been reported to be effective for the structure-controlled growth of single-wall carbon nanotubes (SWCNTs). However, some fundamental issues remain unclear because of the complex catalytic growth environment. Here, we directly investigated the active catalytic phase of Co-W-C alloy catalyst, the growth kinetics of CNTs, and their interfacial dynamics using closed-cell environmental transmission electron microscopy at atmospheric pressure. The alloy catalyst was precisely identified as a cubic ??-carbide phase that remained unchanged during the whole CNT growth process. Rotations of the catalyst nanoparticles during CNT growth were observed, implying a weak interfacial interaction and undefined orientation dependence for the solid catalyst. Theoretical calculations suggested that the growth kinetics are determined by the diffusion of carbon atoms on the surface of the ??-carbide catalyst and through the interface of the catalyst-CNT wall

Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease

Synaptic neurodegeneration is thought to be an early event initiated by soluble β-amyloid (Aβ) aggregates that closely correlates with cognitive decline in Alzheimer disease (AD). Apolipoprotein ε4 (APOE4) is the most common genetic risk factor for both familial AD (FAD) and sporadic AD; it accelerates Aβ aggregation and selectively impairs glutamate receptor function and synaptic plasticity. However, its molecular mechanisms remain elusive and these synaptic deficits are difficult to monitor. AD- and APOE4-dependent plasma biomarkers have been proposed, but synapse-related plasma biomarkers are lacking. We evaluated neuronal pentraxin 1 (NP1), a potential CNS-derived plasma biomarker of excitatory synaptic pathology. NP1 is preferentially expressed in brain and involved in glutamate receptor internalization. NP1 is secreted presynaptically induced by Aβ oligomers, and implicated in excitatory synaptic and mitochondrial deficits. Levels of NP1 and its fragments were increased in a correlated fashion in both brain and plasma of 7–8 month-old E4FAD mice relative to E3FAD mice. NP1 was also found in exosome preparations and reduced by dietary DHA supplementation. Plasma NP1 was higher in E4FAD+ (APOE4+/+/FAD+/−) relative to E4FAD- (non-carrier; APOE4+/+/FAD−/−) mice, suggesting NP1 is modulated by Aβ expression. Finally, relative to normal elderly, plasma NP1 was also elevated in patients with mild cognitive impairment (MCI) and elevated further in the subset who progressed to early-stage AD. In those patients, there was a trend towards increased NP1 levels in APOE4 carriers relative to non-carriers. These findings indicate that NP1 may represent a potential synapse-derived plasma biomarker relevant to early alterations in excitatory synapses in MCI and early-stage AD

Preparation of (Lu,Y)3(Al,Sc,Cr)2Al3O12 phosphor ceramics with high thermal stability for near-infrared LED/LD

Near-infrared (NIR) phosphor-converted light-emitting diodes/laser diodes (LEDs/LDs) are prospective lighting sources for NIR spectroscopy. However, developing NIR phosphor materials with desired thermal robustness and high photoelectric efficiency is a crucial challenge for their applications. In this work, based on the cationic radius matching effect, a series of (Lu,Y)3(Al,Sc,Cr)2Al3O12 NIR phosphor ceramics (LuYScCr NIR-PCs) were fabricated by vacuum sintering. Excellent thermal stability (95%@150 ℃) was obtained in the prepared NIR-PCs, owing to their weak electron–phonon coupling effect (small Huang–Rhys factor). Being excited at 460 nm, NIR-PCs realized a broadband emission (650–850 nm) with internal quantum efficiency (IQE) of 60.68%. Combining NIR-PCs with LED/LD chips, the maximum output power of the encapsulated LED prototype was 447 mW@300 mA with photoelectric efficiency of as high as 18.6 %@180 mA, and the maximum output power of the LD prototype was 814 [email protected] A. The working temperatures of NIR-PCs were 70.8 ℃@300 mA (LED) and 102.8 ℃@3 A (LD). Finally, the prepared NIR-PCs applied in food detection were verified in this study, demonstrating their anticipated application prospects in the future

بررسی حیطه‌های موجود در فرم‌های ارزشیابی از دیدگاه دانشجویان در دانشگاه علوم پزشکی زنجان در سال تحصیلی 86- 87

زمینه و هدف: ارزشیابی استادان متداول‌ترین روش جهت سنجش کیفیت آموزش می‌باشد. دانشجویان بیش از دست‌اندرکاران در جریان روند آموزش قرار‌دارند بنابراین با نظرخواهی از آنان دیدگاه کاملی برای مسئولین در مورد نقاط قوت و ضعف استادان به‌دست می‌آید. هدف از این پژوهش بررسی حیطه‌های موجود در فرم‌های ارزشیابی از دیدگاه دانشجویان در دانشکده‌های پزشکی، پیراپزشکی و پرستاری و مامایی می‌باشد. روش بررسی: این تحقیق به صورت توصیفی انجام گرفت. 1683 برگ ارزشیابی دانشجویان از استادان هیأت علمی (73 نفر) مربوط به دانشکده‌های پزشکی، پیراپزشکی و پرستاری- مامایی بررسی شد. پرسش‌نامه‌ی دانشجویان پزشکی حاوی 15 سؤوال و دانشجویان پیراپزشکی و پرستاری مامایی 21 سؤوال بود که بر اساس مقیاس لیکرات از حیطه‌های مختلف مقرراتی، علمی و آموزشی، نظارتی و نگرشی تشکیل شده بود. نمرات سؤوالات از نمره‌ی 100 محاسبه شد، نمرات بالاتر بیانگر عملکرد مطلوب‌تراستادان می‌باشد. تجزیه و تحلیل داده‌ها به‌صورت آمار توصیفی با نرم‌افزار SPSS انجام شد. یافته‌ها: نتایج نشان داد مقایسه در سطوح کلی بین دانشکده‌ها، دانشکده‌ی پیراپزشکی با میانگین کل و انحراف معیار 61/3 ±50/85 نسبت به سایر دانشکده‌ها برتری دارد. دانشکده‌ی پیراپزشکی در حیطه‌ی مقرراتی با میانگین و انحراف معیار 89/3±01/91، دانشکده‌ی پزشکی در حیطه‌ی نگرشی با میانگین و انحراف معیار 45/5±48/90 و دانشکده‌ی پرستاری مامایی در حیطه‌ی مقرراتی با میانگین و انحراف معیار 25/4±34/88 بیشترین امتیاز را داشتند. نتیجه‌نهایی نشان می‌دهد، حیطه‌ی علمی و آموزشی نسبت به سایر حیطه‌ها در سطح پایین‌تر می‌باشد. نتایج حیطه‌ها (علمی و آموزشی، نظارتی و نگرشی) بین دانشکده‌ها معنی‌دار می‌باشد (0001/0=P). نتیجه‌گیری: به نظر می‌رسد با برنامه‌ریزی جهت برگزاری کارگاه‌های آموزشی، روش تدریس و تحقیق جهت ارتقای آموزش استادان، اعطا‌ی فرصت مطالعاتی و تشویق انجام کارهای تحقیقاتی و پژوهشی گام مؤثری جهت ارتقای سطح علمی و بالاخره عملکرد بالای استادان خواهد بود

Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression

T helper cells that produce IL-17 (Th17 cells) have recently been identified as the third distinct subset of effector T cells. Emerging data suggests that Th17 cells play an important role in the pathogenesis of many liver diseases by regulating innate immunity, adaptive immunity, and autoimmunity. In this study, we examine the role and mechanism of Th17 cells in the pathogenesis of autoimmune hepatitis (AIH). The serum levels of IL-17 and IL-23, as well as the frequency of IL-17+ cells in the liver, were significantly elevated in patients with AIH, compared to other chronic hepatitis and healthy controls. The hepatic expressions of IL-17, IL-23, ROR-γt, IL-6 and IL-1β in patients with AIH were also significantly increased and were associated with increased inflammation and fibrosis. IL-17 induces IL-6 expression via the MAPK signaling pathway in hepatocytes, which, in turn, may further stimulate Th17 cells and forms a positive feedback loop. In conclusion, Th17 cells are key effector T cells that regulate the pathogenesis of AIH, via induction of MAPK dependent hepatic IL-6 expression. Blocking the signaling pathway and interrupting the positive feedback loop are potential therapeutic targets for autoimmune hepatitis