Notes

Essential Roles associated with Lysophospholipid Receptors inside Initial involving Neuroglia in addition to their Neuroinflammatory Reactions.
Taken together, our results demonstrate that PAF plays a crucial role in maintaining the hepatoma cell stemness by β-catenin signaling.Abbreviations CSCs cancer stem cells; HCC hepatocellular carcinoma; PAF pCNA-associated factor.Eukaryotic cells use post-translational modifications to diversify and dynamically coordinate the function and properties of protein networks within various cellular processes. For example, the process of autophagy strongly depends on the balanced action of kinases and phosphatases. Highly conserved from the budding yeast Saccharomyces cerevisiae to humans, autophagy is a tightly regulated self-degradation process that is crucial for survival, stress adaptation, maintenance of cellular and organismal homeostasis, and cell differentiation and development. Many studies have emphasized the importance of kinases and phosphatases in the regulation of autophagy and identified many of the core autophagy proteins as their direct targets. In this review, we summarize the current knowledge on kinases and phosphatases acting on the core autophagy machinery and discuss the relevance of phosphoregulation for the overall process of autophagy.Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, which has been found associated with dysfunctional mitochondria. In order to advance our understanding of the complex molecular mechanisms underlying this disease, we analyzed mitophagy, a process fundamental for the elimination of damaged mitochondria through the autophagic process, in peripheral blood mononuclear cells (PBMCs) of MS patients. Through a genetic analysis carried out on 203 MS patients and 1000 healthy controls, we identified a natural variant of CALCOCO2/NDP52, a well-known autophagic receptor, associated with and protective in MS. Structural modeling of the CALCOCO2 variant and functional studies highlighted an amino acid substitution (G140E) located near the LC3-interacting region (LIR) motif of CALCOCO2, crucial in controlling mitophagy. In addition, we found that among PBMCs, CALCOCO2 is mainly expressed in B cells and, by mediating mitophagy, it reduces pro-inflammatory cytokine production following stimulation of these cells. Here we summarize these recent findings, discuss the putative protective roles of CALCOCO2 in B cells and its novel association with an autoimmune disease such as MS.Abbreviations LIR LC3-interacting region; MS multiple sclerosis; PBMC peripheral blood mononuclear cells; RR-MS relapsing-remitting MS; TLR toll like receptor.As a highly dynamic organelle, mitochondria undergo constant fission and fusion to change their morphology and function, coping with various stress conditions. Loss of the balance between fission and fusion leads to impaired mitochondria function, which plays a critical role in the pathogenesis of Parkinson disease (PD). Yet the mechanisms behind mitochondria dynamics regulation remain to be fully illustrated. Chaperone-mediated autophagy (CMA) is a lysosome-dependent process that selectively degrades proteins to maintain cellular proteostasis. Pilaralisib In this study, we demonstrated that MARCHF5, an E3 ubiquitin ligase required for mitochondria fission, is a CMA substrate. MARCHF5 interacted with key CMA regulators and was degraded by lysosomes. Severe oxidative stress compromised CMA activity and stabilized MARCHF5, which facilitated DNM1L translocation and led to excessive fission. Increase of CMA activity promoted MARCHF5 turnover, attenuated DNM1L translocation, and reduced mitochondria fragmentation, which alleviated mitochondrial dysfunction under oxidative stress. Furthermore, we showed that conditional expression of LAMP2A, the key CMA regulator, in dopaminergic (DA) neurons helped maintain mitochondria morphology and protected DA neuronal viability in a rodent PD model. Our work uncovers a critical role of CMA in maintaining proper mitochondria dynamics, and loss of this regulatory control may occur in PD and underlie its pathogenic process.Abbreviations CMA chaperone-mediated autophagy; DA dopaminergic; DNM1L dynamin 1 like; FCCP carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone; HSPA8 heat shock protein family A (Hsp70) member 8; LAMP2A lysosomal associated membrane protein 2A; MARCHF5 membrane-associated ring-CH-type finger 5; MMP mitochondria membrane potential; OCR oxygen consumption rate; 6-OHDA 6-hydroxydopamine; PD Parkinson disease; SNc substantia nigra pars compacta; TEM transmission electron microscopy; TH tyrosine hydroxylase; TMRE tetramethylrhodamine ethyl ester perchlorate; WT wild type.
Evidence for a genetic influence on psychological treatment outcome so far has been inconsistent, likely due to the focus on candidate genes and the heterogeneity of the disorders treated. Using polygenic risk scores (PRS) in homogenous patient samples may increase the chance of detecting genetic influences.

A sample of 342 phobic patients treated either for clinically relevant dental fear (
 = 189) or other (mixed) phobic fears (
 = 153) underwent highly standardised exposure-based CBT. A brief five-session format was used to treat dental fear, whereas longer multi-session treatments were used with the mixed-fear cohort. PRS were calculated based on large genetic studies of Neuroticism, Educational Attainment (EA), Intelligence, and four psychopathology domains. We compared PRS of post-treatment and follow-up remitters and non-remitters and regressed PRS on fear reduction percentages.

In the dental fear cohort, EA PRS were associated with treatment outcomes, i.e. drop-out, short- and long-term remission state, fear reduction, and attendance of subsequent dental appointments. In the mixed fear treatment cohort, no gene effects were observable.

Results indicate the importance of EA-related traits for outcomes following brief, but not long, standardised exposure-based CBT. Such use of PRS may help inform selection and tailoring of treatments.
Results indicate the importance of EA-related traits for outcomes following brief, but not long, standardised exposure-based CBT. Such use of PRS may help inform selection and tailoring of treatments.Research over the last 10 years suggests that the brain's reward system plays a crucial role in stress resilience. Notably, reward processing includes both an anticipatory (cue-triggered "wanting") phase and a consummatory ("liking") phase. However, previous studies manipulated rewards via direct reward administration, which makes it difficult to isolate the buffering effect of anticipating the reward stimulus. In the current study, we designed a paradigm to manipulate participants into generating reward anticipation or not and investigated whether reward anticipation can buffer psychological, neuroendocrine, and cardiovascular responses to psychosocial stress. A sample of 78 healthy young adults underwent the Trier Social Stress Test or placebo-Trier Social Stress Test after a reward anticipation task. Results showed that reward anticipation relieved subjective stress feelings, as well as the overall cortisol secretion and the increased heart rate induced by psychosocial stress. Taken together, these findings expanded our understanding of the role the reward system plays in stress resilience, and the possible psychological mechanism of the buffering effect for future stress study was also discussed.HIGHLIGHTSReward processing includes both an anticipatory and consummatory phasesThe buffering effect of anticipating the reward stimulus requires elucidationWe examined if said anticipation buffers varied responses to psychosocial stressReward anticipation relieved subjective stress, cortisol secretion, and heart rateWe clarified the role of the reward system in stress resilience.
The Twelve Steps of Alcoholics Anonymous (AA) has proven to be an effective aid in recovery for many people with alcohol use disorder. While constructive criticisms of AA can be beneficial to the organization, other criticisms have merely served as rhetorical devices intent on discrediting the 12-step approach.

This paper examines six prominent critiques of AA, paying special attention to the premises, tone, and factual basis of the statements. Interpretations grounded in AA literature are offered to address claims or critiques around prominent themes, which are organized into two main classes purported causes of alcoholism and factors maintaining alcoholism.

Findings reveal tenuous statements in the AA literature that appear contradictory and thereby invite a misreading. These statements, some of which misrepresent the tenets of AA and its founders, underscore certain vocal criticisms that are not entirely unfounded. While many pages of the AA literature are imbued with timeless wisdom, even the most acohol use disorder. Conclusions/Importance The AA literature essentially presents a valid target for critics, fueling resistance to this free community-based resource that may prevent people who could benefit from AA from seeking the help of the 12-steps.This review aims to develop an evidence-based pathway for isolated adult orbital blowout fractures. Evaluation of assessment methods, outcome measures, imaging modalities, and crucially, the optimal timing of surgical intervention was critically examined to develop a clinically applicable care pathway. A literature search was carried out using Scopus, PubMed and Web of Knowledge. The literature favors the use of HAR% ratio, Field of Binocular Single Vision (FOBSV) and Exophthalmometer as the core tests that should form part of the standardized assessment for blow-out fractures (BOFs). CT imaging remains gold standard, particularly to identify 'red-flags' warranting early intervention. There was some disagreement in relation to timing of intervention in adult fractures who continue to be symptomatic without initial extraocular muscle (EOM) entrapment and enophthalmos >3 mm, where early intervention within two weeks is not indicated. The limited literature available agreed that successful functional and radiological outcomes can be achieved with conservative or late surgical management following an extended observational period of four weeks, opposed to the conventional two weeks. An evidence-based care pathway has been created, confidently including the initial assessment methods, imaging modality, and the criteria for observation. A four-week observational period has been advocated due to evidence suggesting that there is no significant difference in outcomes from two-week observation, plus with careful functional evaluation, surgery may be avoided in some cases.
To identify the clinical characteristics, histopathological features, and prognosis of kidney disease in a large cohort of elderly patients from Northeast China.

We retrospectively analyzed the renal disease spectrum in 7,122 patients who underwent renal biopsies at the Second Hospital of Jilin University from 2006 to 2020. Patients were grouped according to age below 60 years (non-elderly group,
 = 5923) and at least 60 years (elderly group,
 = 1199). The clinical and pathological characteristics of renal biopsy patients in the groups were analyzed using the
-test and chi-square test.

Compared with the non-elderly group, the elderly group had significantly fewer patients with primary glomerulonephritis, but more patients with tubulointerstitial disorders (
 < .05). The incidence of IgA nephropathy, mesangial proliferative glomerulonephritis, and lupus nephritis was significantly lower in elderly patients than in non-elderly patients. The incidence of membranous nephropathy, membranoproliferative glomerulonephritis, diabetic nephropathy, hypertensive nephropathy, systemic vasculitis-associated renal damage, and amyloid nephropathy was significantly higher in elderly patients than in non-elderly patients (
 < .
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