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Distinct Neuronal, Proliferative, and Secretory Pathways are Perturbed in Cancer Survivors with Depressive Symptoms

Introduction Depression is highly prevalent among cancer survivors and may be biologically distinct, although clinical studies investigating these mechanisms remain limited. Thus, the aims of this study were to (1) identify perturbed biological pathways associated with depressive symptom severity in cancer survivors, and (2) investigate whether these pathways are common or distinct to those perturbed in an age-matched non-cancer cohort. Methods We analyzed cross-sectional self-reported and transcriptomic data from the Multi-Ethnic Study of Atherosclerosis (PHD #39341). Cancer survivors and an age-matched non-cancer cohort (target ratio 1:2) were identified. The 20-item Center for Epidemiologic Studies Depression Scale (CES-D) was used to split participants into low (CES-D

From Proteome Mining to Structural Validation: Phosphopyruvate Hydratase as a Structurally Tractable Drug Target in Kinetoplastid Parasites

Chagas disease, caused by Trypanosoma cruzi, demands novel therapeutic strategies that overcome the toxicity and limited efficacy of current treatments. To address this need, herein we report an integrative, target-centric strategy that combines parasite proteome mining, structural modeling, and experimental validation. Functional enrichment and druggability analyses identified phosphopyruvate hydratase (PPH) as a promising candidate due to its essential metabolic role and limited similarity to human homologs. Notably, proteome mining revealed the presence and conservation of PPH across kinetoplastid parasites, including Leishmania donovani, supporting its evaluation beyond T. cruzi. For the selected PPH sequences, AlphaFold-derived three-dimensional models underwent extensive molecular dynamics refinement, yielding stable conformational ensembles suitable for structure-based studies. Using this validated model, virtual screening of the Latin American Natural Products Database - LANaPDB - identified aptosimon as a top-ranked compound candidate. Molecular dynamics simulations further showed ligand-dependent binding behavior, suggesting alternative binding modes distinct from the canonical substrate configuration. In vitro assays demonstrated consistent antiparasitic activity against intracellular T. cruzi amastigotes (IC50 = 3.52 ug/mL) and Leishmania donovani promastigotes (IC50 = 13.06 ug/mL), supporting the biological relevance of the aptosimon-related lignan chemotype, hinokinin, across two kinetoplastid parasite models. Together, these results support PPH as a structurally tractable and biologically relevant candidate target, while identifying an aptosimon-related lignan chemotype, represented experimentally by hinokinin, as a cross-species antiparasitic scaffold that warrants further biochemical target-validation studies.

Population-associated molecular variation in histologically normal breast tissue is context-dependent and associated with distinct transcriptional states

Population-associated molecular variation in breast tissue may contribute to differences in tissue biology and disease susceptibility, yet the extent to which such variation is shaped by underlying tissue states remains unclear. Here, we performed RNA-seq and lipidomic profiling of histologically normal breast tissue samples from African American (AA) and Caucasian White (CW) individuals, followed by conceptual integration of the resulting transcriptomic and lipidomic patterns. Unsupervised analysis revealed two distinct baseline transcriptional states (G1 and G2) that defined the primary axis of molecular variation across the cohort and corresponded to epithelial-enriched (G1) and vascular-enriched (G2) tissue contexts as determined by cell-type deconvolution. Global comparisons between AA and CW samples showed minimal transcriptomic differences, with only a single gene reaching significance after multiple testing correction. However, when stratified by baseline tissue state, 191 genes were differentially expressed within G1, with coordinated upregulation of extracellular matrix organization and proliferative/cytoskeletal processes in AA samples. These patterns were consistently supported across multiple enrichment approaches. No comparable population-associated differences were observed within G2. Lipidomic analyses showed partial but non-significant trends consistent with transcriptomic structure, suggesting that lipid variation provides complementary but limited support for baseline molecular differences, likely reflecting constraints of bulk tissue composition. Together, these findings suggest that population-associated molecular differences in normal breast tissue are context-dependent and emerge within specific baseline transcriptional states, where distinct biological programs can coexist and be differentially modulated. These findings highlight the importance of tissue heterogeneity in shaping molecular variation and its potential relevance to disease-associated tissue states.

Unlocking Latent Dimensions: Exploring Representations of Large-Scale X-ray Scattering Data using Variational Autoencoders

arXiv:2606.14999v1 Announce Type: new Abstract: Scientific user facilities generate X-ray scattering data faster than traditional workflows can process them. We address this challenge across two settings, offline dataset exploration and live on-the-fly analysis. We train a domain-specific attention-based Convolutional Variational Autoencoder (C-VAE) on 1.5 million X-ray scattering images to learn low-dimensional representations capturing structural variation across diverse experimental conditions. The learned latent space reveals well-organized clusters and smooth trajectories reflecting experimental progression. It further supports controlled synthetic scattering image generation across diverse structural states. When deployed without retraining, the model organizes time-resolved film formation experiments at two synchrotron facilities into interpretable latent structures. Benchmarking against DINOv3 (ViT-7B), a general-purpose vision foundation model, demonstrates that domain-specific training yields more interpretable latent organization for scattering data. Both workflows are integrated within Latent Space Explorer, a component of the MLExchange platform, supporting interactive structural exploration across archived datasets and live experiments.