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The apolipoprotein E type ∊4 allele (ApoE4) is known as the strongest genetic risk factor for Alzheimer’s Disease (AD). Meanwhile, many aspects of its impact on AD pathology remain underexplored. This study conducts a systematic data analysisof donor data from the Seattle Alzheimer’s Disease Brain Cell Atlas. Our investigation delves into the intricate interplay between identified biomarkers and their correlation with ApoE4 across all severities of AD. Employing Pearson R correlation, and one-way and two-way ANOVA tests, we elucidate the pathological changes in biomarkers and the altering effects of ApoE4. Remarkably, the phosphorylation of tau observed in neurofibrillary tangles (NFTs) marked by the AT8 antibody, emerges as the most correlated factor with other pathological biomarkers. This correlation is mediated by both tau and amyloid pathology, suggesting a higher hierarchical role in determining AD pathological effects than other biomarkers. However, non-ApoE4 carriers exhibit a more significant correlation with disease progression severity compared to ApoE4 carriers, though ApoE4 carriers demonstrate significance in exacerbating the effect of accumulating phosphorylated tau and amyloid plaques assessed by AT8 and 6E10 antibodies. Furthermore, our analysis does not observe dramatic neuronal changes in grey matter across the span of AD pathology. Glia activation, measured by Iba1 and GFAP, demonstrates an amyloid-specific correlation. This research marks the first human post-mortem analysis providing a comprehensive examination of prevailing AD biomarkers and their interconnectedness with pathology and ApoE4 genetic factor. Limitations in the study are acknowledged, underscoring the need for further exploration and refinement in future research endeavors.

To recognize objects of the unseen classes, most existing Zero-Shot Learning(ZSL) methods first learn a compatible projection function between the common semantic space and the visual space based on the data of source seen classes, then directly apply it to the target unseen classes. However, for data in the wild, distributions between the source and target domain might not match well, thus causing the well-known domain shift problem. Based on the observation that visual features of test instances can be separated into different clusters, we propose a new visual structure constraint on class centers for transductive ZSL, to improve the generality of the projection function (i.e.alleviate the above domain shift problem). Specifically, three different strategies (symmetric Chamfer-distance, Bipartite matching distance, and Wasserstein distance) are adopted to align the projected unseen semantic centers and visual cluster centers of test instances. We also propose two new training strategies to handle the data in the wild, where many unrelated images in the test dataset may exist. This realistic setting has never been considered in previous methods. Extensive experiments demonstrate that the proposed visual structure constraint brings substantial performance gain consistently and the new training strategies make it generalize well for data in the wild. The source code is available at https://github.com/raywzy/VSC.

Focal adhesion kinase (FAK) is a crucial protein component of focal adhesions (FAs) and belongs to the cytoplasmic non-receptor protein tyrosine kinase family. FAK primarily regulates adhesion signaling and cell migration and is highly expressed in various tumors, including lung, liver, gastric, and colorectal cancers, as well as in conditions such as acute lung injury (ALI) and pulmonary fibrosis (PF). Recent research on FAK and its small-molecule inhibitors has revealed that targeting FAK provides a novel approach for treating various lung diseases. FAK inhibitors can obstruct signaling pathways, demonstrating anti-tumor, anti-inflammatory, and anti-fibrotic effects. In lung cancer, FAK inhibitors suppress tumor growth and metastasis; in ALI, they exert protective effects by alleviating inflammatory responses and oxidative stress; and in pulmonary fibrosis, FAK inhibitors reduce fibroblast activation and inhibit collagen deposition. The findings demonstrate promising efficacy and an acceptable safety profile in preclinical models. However, these early-stage results require further validation through clinical studies. Additionally, the underlying mechanisms, as well as the toxic effects and side effects, necessitate further in-depth investigation. Some have progressed to clinical trials (Defactinib (Phase II), PF-562271 (Phase I), CEP-37440 (Phase I), PND-1186 (Phase I), GSK-2256098 (Phase II), BI-853520 (Phase I)), offering potential therapeutic targets for lung diseases. Collectively, these findings establish a foundational basis for the advancement of FAK inhibitor discovery. Emerging methodologies, such as PROTAC degraders and combination regimens, demonstrate significant potential for future research. Based on a comprehensive analysis of the relevant literature from 2015 to the present, this review briefly introduces the structure and function of FAK and discusses recent research advancements regarding FAK and its inhibitors in the context of pulmonary diseases.

Purpose Adolescent and young adult (AYA) cancer patients, aged between 15 to 39 years old, suffer from long-term psychological distress, confronting low self-efficacy and various psychological problems. This study constructs a group online-based peer support intervention combined with offline activities to explore its impact on the psychological distress of AYA cancer patients. Methods A randomized, two-arm clinical trial was conducted in which 90 AYA cancer patients were recruited. The control group ( N  = 45) received conventional psychological care and treatment, and the experimental group ( N  = 45) received 8 weeks of an online peer support intervention. Outcome measures included psychological distress (Distress Thermometer, DT), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), perceived peer support (Cancer Peer Support Scales, CaPSS), and readiness for return to work (Readiness to Return-To-Work Scale, RRTW). Results Eight-week peer support intervention was effective in improving psychological distress, anxiety, and depressive symptoms in the experimental group with statistically significant differences ( P  < 0.05). Time affected psychological distress, anxiety, and depressive symptoms in AYA cancer patients ( P  < 0.05), and there was an interaction with intervention factors ( P  < 0.05). The intervention has a positive effect on relieving the psychological status of AYA cancer patients. For readiness for return to work, the experimental group was in the preparation for the action-behavioral stage immediately, 1 month and 3 months after the end of the intervention ( P  < 0.01), supporting AYA cancer patients who have not returned to work to maintain optimal return-to-work readiness. Conclusions The group online-based peer support intervention is popular and has good scientificity, effectiveness, and practical significance for AYA cancer patients. Trial registration. This study was registered at clinicaltrials.gov. (ChiCTR2100053091, registered on 10 November 2021).

Background Music therapy can improve mood in patients undergoing hematopoietic stem cell transplantation (HSCT). However, live music (LM) delivered by professional music therapists is not common in developing countries owing to the shortage of professional music therapists. Thus, in this study, we explored the effects of a multidisciplinary collaborative intervention based on LM on physical and psychological well-being of adolescent and young adult (AYA) patients undergoing HSCT with a quasi-experimental design. Methods A total of 62 AYA patients agreed to participate and were randomly assigned to the intervention group receiving 4-week LM therapy ( n  = 31) or control group receiving usual care ( n  = 31). Depression, salivary cortisol, fatigue, and quality of life were the main outcome indicators measured at baseline, immediately after the intervention, 1 month, and 3 months follow-up. The intervention effects were analyzed by generalized estimating equations. Results Significant decrease in HADS-D scores occurred in the intervention group compared with wait-list controls at immediately after intervention ( p  < 0.05). Participants in the LM group had greater improvement in quality of life and lower salivary cortisol level than those in the wait-list control group at immediately, 1 month, and 3 months after intervention ( p  < 0.05). However, the interaction effects of the BFI scores were not significant. Conclusions LM therapy significantly alleviated depression and salivary cortisol levels as well as improved quality of life of AYA patients undergoing HSCT.

Background/Aims Chemotherapy resistance in liver cancer is a major clinical issue, with CD147 playing a vital role in this process. However, the specific mechanisms underlying these processes remain largely unknown. This study investigates how CD147 internalization leads to cytoprotective autophagy, contributing to chemotherapy resistance in hepatocellular carcinoma (HCC). Methods Utilizing bioinformatics methods for KEGG pathways enrichment and screening key molecules associated with chemotherapy resistance through analyses of GEO and TCGA databases. An overexpression/knockdown system was used to study how CD147 internalization leads to autophagy in vitro and in vivo. The process was observed using microscopes, and molecular interactions and autophagy flux were analyzed. Analyzing the internalization of CD147 intracellular domains and the interaction with G3BP1 in clinical chemotherapy recurrence HCC tissues by immunohistochemistry, tissue immunofluorescence, and mass spectrometry. A tumor xenograft mice model was used to study cytoprotective autophagy induced by CD147 and test the effectiveness of combining cisplatin with an autophagy inhibitor in nude mice models. Results In our study, we identified the tumor-associated membrane protein CD147, which implicated in chemoresistance lysosome pathways, by evaluating its protein degree value and betweenness centrality using Cytoscape. Our findings revealed that CD147 undergoes internalization and interacts with G3BP1 following treatment with cisplatin and methyl-β-cyclodextrin, forming a complex that is transported to lysosomes via Rab7A. Notably, higher doses of cisplatin enhanced CD147-mediated lysosomal transport while concurrently inhibiting SG assembly. The CD147-G3BP1 complex additionally inhibits mTOR activity, promoting autophagy and augmenting chemoresistance in hepatoma cells. In vivo studies investigations and analyses of clinical samples revealed that elevated internalization of CD147 is associated with chemotherapy recurrence in liver cancer and the maintenance of stem cells. Mice experiments found that the combined administration of cisplatin and hydroxychloroquine enhanced the efficacy of treatment. Conclusions This study reveals that CD147 internalization and CD147-G3BP1 complex translocation to lysosomes induce cytoprotective autophagy, reducing chemotherapy sensitivity by suppressing mTOR activity. It is also shown that chemotherapy drugs combined with autophagy inhibitors can improve the therapeutic effect of cancer, providing new insights into potential targeted therapeutic approaches in treating HCC.

IntroductionCancer diagnosis and treatment can impair fertility, and younger female patients with cancer have a particularly strong need for fertility preservation. Fertility preservation decision aids are thought to help patients make proactive and informed treatment decisions. This systematic review aims to assess the effectiveness and feasibility of online fertility preservation decision aids for young female patients with cancer.Methods and analysisPubMed, Web of Science Core Collection, Embase, The Cochrane Central Register of Controlled Trials, PsycINFO and CHINAL, along with three grey literature sources (Google Scholar, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform), will be searched from each database’s establishment to 30 November 2022. Two trained reviewers will independently screen the articles, and the data extraction and methodological quality of eligible randomised controlled trials and quasiexperimental studies will be assessed. A meta-analysis will be performed using Review Manager V.5.4 (Cochrane Collaboration) software, and heterogeneity will be assessed using I² statistics. If a meta-analysis is not possible, a narrative synthesis will be done.Ethics and disseminationSince this systematic review is based on published data, no ethical approval is required. The study’s findings will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration numberCRD42022363287.

Background and aims: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with extremely high short-term mortality. Whether plasma exchange (PE) improves HBV-ACLF outcomes remains controversial. Here, PE-based non-bioartificial liver support system (NB-ALSS) effects on short-term HBV-ACLF patient outcomes were investigated. Materials and methods: HBV-ACLF patients from Chinese Acute-on-chronic Liver Failure (CATCH-LIFE) cohort receiving standard medical therapy (SMT) alone or PE-based NB-ALSS in addition to SMT were allocated to SMT and SMT+PE groups, respectively; propensity score matching (PSM) was used to eliminate confounding bias. Short-term (28/90-day and 1-year) survival rates were calculated (Kaplan-Meier). Results: In total, 524 patients with HBV-ACLF were enrolled in this study; 358 received SMT alone (SMT group), and the remaining 166 received PE-based NB-ALSS in addition to SMT (SMT+PE group). PSM generated 166 pairs of cases. In the SMT+PE group, 28-day, 90-day, and 1-year survival rates were 11.90, 8.00, and 10.90%, respectively, higher than those in the SMT group. Subgroup analysis revealed that PE-based NB-ALSS had the best efficacy in patients with ACLF grade 2 or MELD scores of 30–40 (MELD grade 3). In MELD grade 3 patients who received SMT+PE, 28-day, 90-day, and 1-year survival rates were improved by 18.60, 14.20, and 20.10%, respectively. According to multivariate Cox regression analysis, PE-based NB-ALSS was the only independent protective factor for HBV-ACLF patient prognosis at 28 days, 90 days, and 1 year (28 days, HR = 0.516, p = 0.001; 90 days, HR = 0.663, p = 0.010; 1 year, HR = 0.610, p = 0.051). For those who received SMT+PE therapy, PE-based NB-ALSS therapy frequency was the only independent protective factor for short-term prognosis (28-day, HR = 0.597, p = 0.001; 90-day, HR = 0.772, p = 0.018). Conclusions: This multicenter prospective study showed that the addition of PE-based NB-ALSS to SMT improves short-term (28/90 days and 1-year) outcomes in patients with HBV-ACLF, especially in MELD grade 3 patients. Optimization of PE-based NB-ALSS may improve prognosis or even save lives among HBV-ACLF patients.

Bisphenol A (BPA) and its structural analogs (bisphenol S (BPS) and bisphenol F (BPF)) are widely consumed endocrine disrupting chemicals that may contribute to the etiology of obesity. To date, few studies have directly investigated the sex-related associations between bisphenols and body fat distribution in adults. In this study, we included 2669 participants from the National Health and Nutrition Examination Survey (NHANES) 2011–2016 to evaluate and compare sex-specific differences of the associations of BPA, BPS, and BPF with body fat distribution. We found that there were significant positive correlations between BPS and body fat indices (STFAT [adjusted β =1.94, 95% CI: (0.24, 3.64)], TAF [0.18 (0.04, 0.32)], SAT [0.15 (0.03, 0.27)], android fat mass [0.20 (0.004, 0.40)], BMI [1.63 (0.61, 2.65)], and WC [3.19 (0.64, 5.73)] in the highest quartiles of BPS), but not in BPA and BPF. Stratified analyses suggested that the significant associations of BPS with body fat indices were stronger in women than men (STFAT [adjusted β =3.75, 95% CI: (1.04, 6.45) vs. adjusted β =−0.06, 95% CI: (−2.23, 2.11), P for interaction < 0.001], TAF [ 0.32 (0.09, 0.54) vs. 0.01 (−0.17, 0.19), P for interaction < 0.001], SAT [0.27 (0.09, 0.45) vs. 0.01 (−0.14, 0.16), P for interaction < 0.001], android fat mass [0.41 (0.12, 0.71) vs. −0.02 (−0.28, 0.24), P for interaction < 0.001], gynoid fat mass [0.56 (0.11, 1.01) vs. −0.05 (−0.41, 0.31), P for interaction = 0.002], BMI [2.76 (1.08, 4.44) vs. 0.47 (−0.80, 1.74), P for interaction < 0.001], and WC [5.51 (1.44, 9.58) vs. 0.61 (−2.67, 3.88), P for interaction < 0.001]), and positive associations between BPS with fat distribution were also observed in non-smoking women. Our study indicated that in women, higher concentration of urinary BPS was associated with increased body fat accumulation, except for visceral adipose tissue mass. These findings emphasize the role of environmental BPS exposure in the increasing fat deposits, and confirm the need for more prospective cohort studies on a sex-specific manner.