Identifying meaningful drug response biomarkers from public pharmacogenomic datasets with biologically informed interpretable neural networks.

With the advancements of next-generation sequencing, publicly available pharmacogenomic datasets from cancer cell lines provide a handle for developing predictive models of drug responses and identifying associated biomarkers. However, many currently available predictive models are often just used as black boxes, lacking meaningful biological interpretations. In this study, we made use of open-source drug response data from cancer cell lines, in conjunction with KEGG pathway information, to develop sparse neural networks, K-net, enabling the prediction of drug response in EGFR signaling pathways and the identification of key biomarkers.

Exploring why adolescents of disadvantaged family socio-economic status were more depressed than others: Serial mediations via personal psychological resources, loneliness, and school refusal functions.

Background: Disadvantageous family socio-economic status (DFSES) is a potential source of disparity in adolescent mental health. This study investigated the association between DFSES and probable depression and its mediation mechanisms via personal psychological resources (hope and resilience), loneliness, and school refusal functions.

Methods: A school-based anonymous survey was conducted among 8285 middle school students in China from February to March 2022; the response/eligible rate was 98.

Sex differences in social anxiety: A longitudinal serial mediation via perceived stress and resilience among adolescents in China.

Background: Adolescent social anxiety is consequential. There is a substantial sex difference in the prevalence. Yet, the underlying mechanisms are almost unknown; no longitudinal studies have investigated this topic.

Challenging gender essentialism with animal examples: Reducing children's prejudice toward voice-based gender nonconformity.

Grounded in developmental intergroup theory, which highlights the role of essentialist thinking in the emergence of prejudice, this study examined whether reducing children's gender essentialism could decrease prejudice against speakers with gender-nonconforming (GN) voices. A total of 162 children aged 8-12 years participated in the study. The intervention group (N = 81) received three lessons illustrating diversity in sex-related traits and behaviors in the animal kingdom to challenge essentialist beliefs about gender roles, expression, and biological sex, whereas the control group received comparable lessons without gender-related content.

Noninvasive assessment of glymphatic system alterations as potential biomarkers for predicting overall survival in glioma.

Objective: In this retrospective study, authors aimed to evaluate the glymphatic function alterations associated with glioma and explore the prognostic value of these alterations by calculating the index for diffusivity along the perivascular space (ALPS index).

Methods: The authors utilized data from the publicly available University of California San Francisco Preoperative Diffuse Glioma MRI (UCSF-PDGM) dataset, which includes 501 adult patients with histopathologically confirmed diffuse glioma, per the 2021 WHO classification, who underwent preoperative MRI, initial tumor resection, and tumor genetic testing at a single medical center from 2015 to 2021.The ALPS index was calculated from diffusivity maps for noninvasive glymphatic system (GS) analysis.

Parent-Adolescent Congruence and Incongruence in Parental Involvement and Academic Achievement: The More, the Better?

Parents and adolescents can differ in their perceptions of parental involvement, yet most research relies on a single informant, potentially overlooking important discrepancies. Using data from 89,448 fifteen-year-olds (50.3% female) and their parents (78.

Nonlinear Associations of Depression and Stigma With Subclinical Hikikomori in Cancer Survivors.

Background: Cancer survivors often experience depression and stigma associated with chronic diseases, which may increase the risk of subclinical hikikomori.

Aims: This study examined the prevalence of subclinical hikikomori and its nonlinear associations with depression and stigma among cancer patients.

Methods: A cross-sectional survey was conducted among 1951 cancer survivors.

Promoter or inhibitor? The role played by housing prices on entrepreneurial vitality in China.

This study delves into the time-varying causal relationship between housing prices (HP) and entrepreneurial vitality (EV) in China, employing a rolling-window sub-sample testing approach. The findings reveal that HP exerts both positive and negative influences on EV across different sub-samples. Specifically, when wealth effects dominate, HP positively impacts EV, acting as a promoter.

Epidermal Growth Factor Receptor (EGFR)-Targeting Peptides and Their Applications in Tumor Imaging Probe Construction: Current Advances and Future Perspectives.

The epidermal growth factor receptor (EGFR) is a key target for both cancer diagnosis and therapeutic interventions. Assessing EGFR expression before therapy has become routine in clinical practice, yet current methods like biopsy and immunohistochemistry (IHC) have significant limitations, including invasiveness, limited repeatability, and lack of real-time, whole-body data. EGFR-targeted imaging has emerged as a promising alternative.

Biomimetic semiconducting polymer dots for dual targeted NIR-II phototheranostic and multimodal coordinated immunostimulatory therapy.

Breast cancer is a global health challenge necessitating more precise and effective treatment strategies. In this study, we developed a novel drug-loaded therapeutic nanoplatform, OCPdots@CTe, which integrated near-infrared-II (NIR-II) window phototheranostic for targeted treatment of orthotopic breast tumors. The outer membrane vesicles (OMVs) can stimulate more immune responses based on precise targeting, while chelerythrine (CTe) can induce apoptosis by generating reactive oxygen species (ROS), thereby enhancing the therapeutic effect.

Versatile Applications of CRISPR-Based Programmable T-DNA Integration in Plants.

Agrobacterium-mediated T-DNA integration into plant genomes represents a cornerstone for transgenic expression in plant basic research and synthetic biology. However, random T-DNA integration can disrupt essential endogenous genes or compromise transgene expression, stressing the need for targeted integration strategies. Here we explored CRISPR-aided targeted T-DNA integration (CRISTTIN) in Arabidopsis, leveraging CRISPR-induced double-strand breaks (DSBs) to facilitate precise T-DNA insertion.

Genetic modifications boost chrexanthomycin yield and neuroprotective potential.

Introduction: Chrexanthomycins, a unique class of pentangular polyphenols (PPs) conjugated with glucuronic acid, have demonstrated remarkable neuroprotective properties both in vitro and in vivo. However, their low yield has restricted their potential applications.

Objective: This study aims to clarify the biosynthetic pathway and neuroprotective potency of chrexanthomycins, enhance their large-scale production potential, and discover novel derivatives with improved activities.

Fici hirtae radix alleviates influenza A virus-induced acute lung injury via TLR4-PI3K-AKT/p38 MAPK-NF-κB signaling pathway.

Ethnopharmacological Relevance: Fici hirtae radix (FHR), documented in the classical Chinese medicinal text "The Characteristics, Uses and Preparation of Medicinal Herbs", has demonstrated clinical efficacy in alleviating respiratory infections. However, its anti-influenza effects and mechanisms remain unclear, dramatically restricting its product development.

Aim Of The Study: This study aimed to explore the protective effects of FHR against acute lung injury (ALI) and its underlying mechanisms.

Exploring the heterogeneity of internet gaming disorder: a stage-based framework characterized by evolving euphoria and compulsivity.

Introduction: Existing diagnosis systems, such as DSM-5 and ICD-11, predominantly rely on a dichotomous approach, flat, cross-sectional definitions of Internet Gaming Disorder (IGD) that fail to capture the persistent, evolving nature and may contribute to heterogeneity. Applying a clinical staging approach, we propose that IGD spans a continuum with early stages marked by euphoria from gaming and later stages by compulsive gaming. This study aimed to empirically identify distinct IGD stages.

Microenvironment-driven transformable self-assembly nanoplatform enables spatiotemporal remodeling for rheumatoid arthritis therapy.

The aberrant vasculature within the inflamed joint cavity of rheumatoid arthritis (RA) not only exacerbates joint pathology but also restricts the effective delivery of therapeutic drugs. Herein, we propose a strategy that involves the rapid and sustained vasculature repair alongside microenvironment-driven drug delivery to achieve multifaceted RA management. The transformable, self-assembling nanoplatform specifically accumulates in the inflamed joint cavity guided by a vascular targeting peptide (STP).

A Citrate Synthase Splice Variant Rewires the TCA Cycle to Promote Colorectal Cancer Progression.

Metabolic reprogramming, notably alterations in the tricarboxylic acid (TCA) cycle, has emerged as a hallmark of cancer that supports tumor growth and metastasis. Despite the TCA cycle being a classical central metabolic pathway, further exploration is needed to fully elucidate the intricate manifestations and contributory mechanisms of TCA cycle rewiring in colorectal carcinogenesis. Herein, we identified a splicing isoform of citrate synthase (CS), CS-ΔEx4, and unveiled its role in TCA cycle dysregulation in colorectal cancer (CRC).

Action verbs and demonstrative pronouns affect volumetric affordance activation.

Whereas the influence of visual information on the activation of perceived affordances is well documented, far less attention has been given to the specific role of language in modulating affordance activation. Furthermore, while several studies have demonstrated that nouns and verbs denoting grasping actions and graspable objects may potentiate affordances, there is little-to-no research exploring similar properties of other word classes, particularly those specifically marking spatial relations - the so-called demonstrative pronouns. Demonstratives (e.

Volatility spillover between financial assets and transport energy.

This study examines the dynamics of volatility spillover between financial assets and transport energy. Such spillovers are critical for implementing risk management strategies, supporting energy policymaking, and enabling more effective investment decisions in today's globally integrated financial-energy system. Our study includes financial assets (both non-green and green) and transport energy (fossil fuels and biofuels).

Beyond efficacy parity: a novel cost-equilibrium framework for value assessment of competing third-line therapies in metastatic colorectal cancer.

Background: Colorectal cancer remains a leading cause of global cancer mortality, with metastatic CRC (mCRC) requiring sequential therapies after first line treatment failure. While regorafenib and fruquintinib are guideline-endorsed third-line options, their comparative value remains unestablished due to absent head-to-head trials. This real-world study evaluates clinical outcomes, safety, and cost differentials to model value-equilibrium pricing.

Emotion word is an ambiguous concept: dividing, defining, and connecting emotion-label words and emotion-laden words.

We argue that emotion words can be divided into two subcategories: emotion-label words and emotion-laden words. We believe that the term "emotion word" should not solely refer to emotion-label words, since emotion-laden words also contain emotional content, and both emotion-label words and emotion-laden words play important roles in creating emotions. Based on the division of emotion-laden words and emotion-label words, the two types of words can be defined by measuring their emotional prototypicality, along with lexicographic definitions and syntactic analyses.

Therapeutic restoration of mitochondria-endoplasmic reticulum cross talk for osteoarthritis.

Osteoarthritis is a prevalent joint disease in the aging population. The hallmark of osteoarthritis is the degeneration of the joint cartilage, characterized by changes in chondrocytes including mitochondrial dysfunction. However, the precise mechanisms of how this affects chondrocyte homeostasis and whether such processes can be explored as therapeutic targets for osteoarthritis remain unclear.

Integrated screening identifies GPR31 as a key driver and druggable target for metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is a globally prevalent but intractable disease lacking effective pharmacotherapies. Here, we performed an integrated multilayered screening for pathogenic genes and druggable targets for MASH. We identified the subclass of metabolite-sensing G protein-coupled receptors, specifically GPR31, a critical contributor to MASH occurrence, which, to our knowledge, was previously uncharacterized.

Inferring Personality From Social Media Activity Using Large Language Models: Cross-Model Agreement, Temporal Stability, and Convergent Validity With Self-Reports.

Introduction: Large language models (LLMs) offer a promising approach to infer personality traits unobtrusively from digital footprints. However, the reliability and validity of these inferences remain underexplored.

Method: Gemini 1.

Supramolecular Microspheres Fabricated from Macrocycle-Incorporated Polymers and Their Biomedical Applications Based on Host-Guest Recognition.

Microspheres have emerged as a pivotal platform for micron-scale drug delivery, yet their utility has been greatly hindered by limitations in biodegradability, drug loading efficiency, and release kinetics, underscoring the urgent need for a next-generation microsphere platform that integrates high performance, scalability, and multifunctionality. Leveraging host-guest recognition, a series of macrocycle-incorporated polymers is synthesized and engineered a new class of supramolecular microspheres, which feature precisely tunable components, including host molecules, guest cargoes, and polymer components, as well as customizable morphologies, while enabling cost-effective, large-scale production. Following systematic validation of the host-guest recognition between β-cyclodextrin (β-CD) and lanreotide, we developed supramolecular microspheres (LAN@S-CPMs) that achieve a drug loading capacity and release duration approximately twice that of conventional microspheres, effectively curbing the disease progression of acromegaly.