Aerobic exercise prevents renal osteodystrophy via irisin-activated osteoblasts.

Renal osteodystrophy is commonly seen in patients with chronic kidney disease (CKD) due to disrupted mineral homeostasis. Given the impaired renal function in these patients, common anti-resorptive agents, including bisphosphonates, must be used with caution or even contraindicated. Therefore, an alternative therapy without renal burden to combat renal osteodystrophy is urgently needed.

Elevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma.

Metabolic reprogramming shapes tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of pro-tumor macrophages, and reduced cytotoxic T cell in the TME.

Interplay between Skeletal Muscle Catabolism and Remodeling of Arteriovenous Fistula via YAP1 Signaling.

Background: Arteriovenous (AV) fistulas are the preferred access for dialysis but have a high incidence of failure. This study aims to understand the crosstalk between skeletal muscle catabolism and AV fistula maturation failure.

Methods: Skeletal muscle metabolism and AV fistula maturation were evaluated in mice with chronic kidney disease (CKD).

Attention-aware differential learning for predicting peptide-MHC class I binding and T cell receptor recognition.

The identification of neoantigens is crucial for advancing vaccines, diagnostics, and immunotherapies. Despite this importance, a fundamental question remains: how to model the presentation of neoantigens by major histocompatibility complex class I molecules and the recognition of the peptide-MHC-I (pMHC-I) complex by T cell receptors (TCRs). Accurate prediction of pMHC-I binding and TCR recognition remains a significant computational challenge in immunology due to intricate binding motifs and the long-tail distribution of known binding pairs in public databases.

Novel genetic insight for psoriasis: integrative genome-wide analyses in 863 080 individuals and proteome-wide Mendelian randomization.

Psoriasis affects a significant proportion of the worldwide population and causes an extremely heavy psychological and physical burden. The existing therapeutic schemes have many deficiencies such as limited efficacies and various side effects. Therefore, novel ways of treating psoriasis are urgently needed.

Graph contrastive learning of subcellular-resolution spatial transcriptomics improves cell type annotation and reveals critical molecular pathways.

Imaging-based spatial transcriptomics (iST), such as MERFISH, CosMx SMI, and Xenium, quantify gene expression level across cells in space, but more importantly, they directly reveal the subcellular distribution of RNA transcripts at the single-molecule resolution. The subcellular localization of RNA molecules plays a crucial role in the compartmentalization-dependent regulation of genes within individual cells. Understanding the intracellular spatial distribution of RNA for a particular cell type thus not only improves the characterization of cell identity but also is of paramount importance in elucidating unique subcellular regulatory mechanisms specific to the cell type.

A comprehensive benchmarking for evaluating TCR embeddings in modeling TCR-epitope interactions.

The complexity of T cell receptor (TCR) sequences, particularly within the complementarity-determining region 3 (CDR3), requires efficient embedding methods for applying machine learning to immunology. While various TCR CDR3 embedding strategies have been proposed, the absence of their systematic evaluations created perplexity in the community. Here, we extracted CDR3 embedding models from 19 existing methods and benchmarked these models with four curated datasets by accessing their impact on the performance of TCR downstream tasks, including TCR-epitope binding affinity prediction, epitope-specific TCR identification, TCR clustering, and visualization analysis.

Risk assessment of persistent incidental pulmonary subsolid nodules to guide appropriate surveillance interval and endpoints.

Guidelines for the follow-up of pulmonary subsolid nodule (SSN) vary in terms of frequency and criteria for discontinuation. We aimed to evaluate the growth risk of SSNs and define appropriate follow-up intervals and endpoints. The immediate risk (IR) and cumulative risk (CR) of SSN growth were assessed using the Kaplan-Meier method according to nodule consistency and size.

Increased plasma interleukin-1β is associated with accelerated lung function decline in non-smokers.

Interleukin-1β is one of the major cytokines involved in the initiation and persistence of airway inflammation in chronic obstructive pulmonary disease (COPD). However, the association between plasma interleukin-1β and lung function decline remains unclear. We aimed to explore the association between plasma interleukin-1β and lung function decline.

The diagnostic performance and optimal strategy of cone beam CT-assisted bronchoscopy for peripheral pulmonary lesions: A systematic review and meta-analysis.

Cone-beam computed tomography (CBCT) assisted bronchoscopy shows prospective advantages in diagnosing peripheral pulmonary lesions (PPLs), but its diagnostic value and potential influencing factors remain unclear. What is the clinical value and optimal strategy of CBCT-assisted bronchoscopy in diagnosing PPLs? The references were searched from PubMed, EmBase, and Web of Science. Studies reporting diagnostic yield and potential influencing factors of CBCT-assisted bronchoscopy were included.

Ultrasound-Activated Copper Matrix Nanosonosensitizer for Cuproptosis-Based Synergy Therapy.

Cuproptosis exhibits enormous application prospects in treatment. However, cuproptosis-based therapy is impeded by the limited intracellular copper ions, the nonspecific delivery, uncontrollable release, and chelation of endogenous overproduced glutathione (GSH). In this work, an ultrasound-triggered nanosonosensitizer (p-TiO-Cu(I)) was constructed for Cu(I) delivery, on-demand release, GSH consumption, and deeper tissue response.

Artificial Intelligence in Retrosynthesis Prediction and its Applications in Medicinal Chemistry.

Retrosynthesis is a strategy to analyze the synthetic routes for target molecules in medicinal chemistry. However, traditional retrosynthesis predictions performed by chemists and rule-based expert systems struggle to adapt to the vast chemical space of real-world scenarios. Artificial intelligence (AI) has revolutionized retrosynthesis prediction in recent decades, significantly increasing the accuracy and diversity of predictions for target compounds.

Automatic Quality Control System and Adenoma Detection Rates During Routine Colonoscopy: A Randomized Clinical Trial.

Importance: High-quality colonoscopy reduces the risks of colorectal cancer by increasing the adenoma detection rate. Routine use of an automatic quality control system (AQCS) to assist in colorectal adenoma detection should be considered.

Objective: To evaluate the effect of an AQCS on the adenoma detection rate among colonoscopists who were moderate- and low-level detectors during routine colonoscopy.

Argonaute-mediated dual recognition enables the detection of trace single-nucleotide-mutated fungicide-resistant fungal pathogens.

Detection of low-abundance mutations for the early discovery of fungicide-resistant fungal pathogens is highly demanded, but remains challenging. Herein, we developed a dual-recognition strategy, termed PARPA, involving s Argonaute (pfAgo)-mediated elimination of wild-type fungal genes and CRISPR/Cas12a-based amplicon recognition. This assay can detect fungicide-resistant at relative abundances as low as 0.

Adjuvant Atezolizumab for Early Triple-Negative Breast Cancer: The ALEXANDRA/IMpassion030 Randomized Clinical Trial.

Importance: Triple-negative breast cancer is an aggressive subtype with a high incidence in young patients, a high incidence in non-Hispanic Black women, and a high risk of progression to metastatic cancer, a devastating sequela with a 12- to 18-month life expectancy. Until recently, one strategy for treating early-stage triple-negative breast cancer was chemotherapy after surgery. However, it was not known whether the addition of immune therapy to postsurgery chemotherapy would be beneficial.

Composition Conversion-Induced Disassembly of Amphiphilic ABA Triblock Copolymer Vesicles: A Monte Carlo Study.

The composition conversion in block copolymer induced by external stimuli such as light and pH is an effective strategy to trigger the disassembly of vesicles experimentally. Based on this strategy, the disassembly behavior of the ABA triblock copolymer vesicle induced by the composition conversion from B block to C block was studied using Monte Carlo simulation. In this study, a part of the B block in the ABA triblock copolymer was converted to the new block C with weaker hydrophobicity, forming the ABCA tetrablock copolymer.

Registered reports in psychology across scholarly citations and public dissemination: A comparative metaevaluation of more than a decade of practice.

After more than a decade of practice, registered reports (RRs) are widely adopted in psychology. However, the acceptance of RRs in terms of postpublication academic recognition and public dissemination, compared with nonregistered reports (non-RR), remained largely unexplored. This matched meta-evaluation identified and analyzed 119 pairs of original research articles (RR vs.

The involuntary experience of digital exclusion among older adults: A taxonomy and theoretical framework.

The emerging phenomenon of digital exclusion raises an important issue that not everyone is equally engaged in and can benefit from the digital world. Older adults are particularly susceptible to digital exclusion, but a comprehensive conceptual treatment of digital exclusion in older adults is lacking in the psychology literature. In this article, we provide a taxonomy to advance the literature on digital exclusion in older adults, identifying key conceptual attributes of older adults' digital exclusion experiences by articulating both structural (i.

Proximity-Induced Superconductivity in Ferromagnetic FeGeTe and Josephson Tunneling through a van der Waals Heterojunction.

Synergy between superconductivity and ferromagnetism may offer great opportunities in nondissipative spintronics and topological quantum computing. Yet at the microscopic level, the exchange splitting of the electronic states responsible for ferromagnetism is inherently incompatible with the spin-singlet nature of conventional superconducting Cooper pairs. Here, we exploit the recently discovered van der Waals ferromagnets as enabling platforms with marvelous controllability to unravel the myth between ferromagnetism and superconductivity.

Exploring the Role of TRAF6-TAK1 Pathway in Podocyte Pyroptosis and Its Implications for Primary Membranous Nephropathy Therapy.

Primary membranous nephropathy (PMN) is a prevalent renal disorder characterized by immune-mediated damage to the glomerular basement membrane, with recent studies highlighting the significant role of pyroptosis in its progression. In this study, we investigate the molecular mechanisms underlying PMN, focusing on the role of Tumor necrosis factor receptor-associated factor 6 (TRAF6) in promoting disease advancement. Specifically, we examine how TRAF6 facilitates PMN progression by inducing the ubiquitination of Transforming growth factor-beta-activated kinase 1 (TAK1), which in turn activates the Gasdermin D (GSDMD)/Caspase-1 axis, leading to podocyte pyroptosis.