A fibroblast-centric network drives cold fibrosis in the tumor microenvironment of lung squamous cell carcinoma.

The tumor microenvironment (TME) of chronic inflammation-associated cancers (CIACs) is shaped by cycles of injury and maladaptive repair, yet the principles organizing fibrotic stroma in these tumors remain unclear. Here, we applied the concept of hot versus cold fibrosis, originally credentialed in non-cancerous fibrosis of heart and kidney, to lung squamous cell carcinoma (LUSC), a prototypical CIAC. Single-cell transcriptomics of matched tumor and adjacent-normal tissue from 16 treatment-naive LUSC patients identified a cold fibrotic architecture in the LUSC TME: cancer-associated fibroblasts (CAFs) expanded and adopted myofibroblast and stress-response states, while macrophages were depleted.

Functional genetic screens reveal key pathways instructing the molecular phenotypes of tumor-associated macrophages.

Tumor-associated macrophages (TAMs) display remarkable functional heterogeneity, yet the molecular mechanisms driving their diverse phenotypes remain elusive. Using CRISPR screens in primary macrophages, we identified tumor-derived factors, including lactic acid, PGE2, and GM-CSF, as key modulators of TAM polarization. These factors interact synergistically and antagonistically to shape distinct TAM phenotypes that are highly conserved across human cancers.

Exploration Progress on Inflammatory Responses and Immune Regulatory Mechanisms in Diabetic Retinopathy.

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes. In recent years, with the number of diabetic patients increasing annually, the number of DR patients has also been rising, and it has become one of the major blinding eye diseases worldwide. The pathogenesis of DR has not been fully clarified but includes microvascular lesions and metabolic factors.

Perturbation of calreticulin potentiates CD8+ T cell-mediated antitumor immunity.

Effective immunotherapy relies on the presentation of tumor-derived neoantigens on the major histocompatibility complex class I (MHC-I) to activate CD8+ T cells. Deficiencies in this process are a key mechanism of immune evasion and resistance to checkpoint blockade. In this study, using an in vivo CRISPR-Cas9 screen, we unexpectedly found that inactivation of calreticulin (CALR), and other selected components of the peptide-loading complex (PLC), induced robust CD8+ T cell-mediated immune responses.

Emission of Acoustic Point Sources near an Interface.

The emission of point sources is a cornerstone of wave-based physics, underpinning applications in optics and acoustics. While optical theories for point sources near interfaces are well established, a unified acoustic framework, modeled after its optical counterpart to provide cohesive insights into emission behaviors, remains underdeveloped. In this Letter, we extend the optical framework to acoustics, focusing on point sources near solid-fluid interfaces.

[Double J-tube indwelling after transurethral seminal vesiculoscopy reduces recurrence of ejaculatory duct obstruction].

Objective: To introduce a surgical method involving the indwelling of double-J tubes (DJT) in the seminal vesicles after transurethral seminal vesiculoscopy (TSV) in order to reduce the recurrence of refractory ejaculatory duct obstruction (EDO).

Methods: This randomized controlled trial included 67 EDO patients undergoing TSV in our hospitals, 27 with (the trial group) and 29 without postoperative indwelling of DJTs in the seminal vesicles (the control group). We collected the general information on the patients and TSV-related parameters, including age, body mass index (BMI), preoperative use of antibiotics, history of urinary tract disease, operation time, hospital stay and intra- and postoperative complications, and performed comparative analyses particularly on the surgical effect, complications, recurrence rate and time to recurrence in the two groups of patients.

Non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol is a predictor for cardiovascular mortality in patients with diabetes mellitus.

Background: The non-high-density lipoprotein cholesterol (non-HDL-C)/HDL-C ratio (NHHR) is linked to cardiovascular event risk, but its prognostic value in diabetes mellitus (DM) patients remains unclear.

Aim: To explore the association of NHHR and cardiovascular mortality in patients with DM and generate predictive model.

Methods: This cohort study analyzed data from 8425 DM patients in National Health and Nutrition Examination Survey.

Concerted changes in Epithelium and Stroma: a multi-scale, multi-omics analysis of progression from Barrett's Esophagus to adenocarcinoma.

Esophageal adenocarcinoma arises from Barrett's esophagus, a metaplastic condition. Multi-omics profiling, integrating single-cell transcriptomics, extracellular matrix proteomics, tissue mechanics and spatial proteomics of the paths of progression from squamous epithelium through metaplasia, dysplasia to adenocarcinoma, in 107 samples from 26 patients in two independent cohorts, defined shared and patient-specific progression characteristics. Metaplastic replacement of epithelial cell composition and architecture was paralleled by changes in stromal cells, extracellular matrix (ECM) and tissue stiffness.

A Fibroblast State Choreographs an Epithelial YAP-dependent Regenerative Program Essential to (Pre)malignancy via ECM-mediated Mechanotransduction.

Unlabelled: Chronic lung injury generates metaplasia which occasionally, but ominously, progresses to squamous dysplasia and squamous lung cancer. To identify mechanisms through which disrupted tissue homeostasis contributes to malignant initiation and progression, we used and heterotypic recombinant models of human b ronchial e pithelial c ells (hBECs) and fibroblasts. We demonstrate that injury-associated TGF-β signaling creates a fibroblast state dependent upon HSP47 upregulation.

Computational insights into the origins of regio- and enantioselectivities in palladium-catalyzed allylic substitution reactions.

Pd-catalyzed allylic substitution reactions represent one of the most important and straightforward protocols for the construction of C-C and C-X bonds. In recent years, significant progress has been made in theoretical studies of these reactions, including proposals of the inner-sphere and outer-sphere nucleophilic attack transition state models, particularly with further elucidation of the origins of regio- and enantioselectivities, based on these key models which serve as the selectivity-determining step. This review focus on elucidating the origins of regio- and enantioselectivities within the framework of selectivity-determining nucleophilic attack transition state models, based on density functional theory calculations.

High-throughput single cell motility analysis using nanowell-in-microwells.

Cell motility is important to many biological processes including cancer, immune response, and tissue repair. Conventional assays measure bulk cell motility, potentially overlooking important heterogeneity and missing important high motility subpopulations. Here, we introduce a high-throughput single-cell motility assay using nanowell-in-microwell plates to precisely track single cell position and analyze their migratory trajectories.

Analysis of the correlation between mental status and ocular and systemic indicators in patients with primary angle-closure glaucoma.

Background: To analyze the poor mental status of patients with primary closed-angle glaucoma(PACG), and to explore the correlation between mental status and ocular and systemic indices in patients with PACG.

Methods: We collected patients' axial length (AL), anterior chamber depth (ACD), nerve fiber layer thickness (RNFL), cup-to-disc ratio (C/D), antinuclear antibody (ANA), toxoplasmosis antibody (anti-Toxoplasma gondii IgM), and anxiety and depression scores (HAMA and HAMD scales). Statistical analysis was utilized to analyze the data for each of the patients in the PACG and cataract patient groups.

Association between left atrial appendage volume and atrial fibrillation recurrence after catheter ablation: a systematic review and meta-analysis.

Objectives: To evaluate the association between left atrial appendage volume (LAAV) and atrial fibrillation (AF) recurrence after catheter ablation (CA) and explore the potential mechanism.

Design: Systematic review and meta-analysis.

Data Sources: PubMed, EMBASE, Web of Science and Cochrane Library databases were searched systematically from inception through 28 September 2024 to identify relevant studies.

Femtosecond laser-assisted printing of hard magnetic microrobots for swimming upstream in subcentimeter-per-second blood flow.

Magnetic microrobots have garnered increasing attention in the biomedical field due to their wireless motion control and noninvasive therapeutic potential. However, current microrobots fabricated from soft magnetic materials exhibit critical limitations, including weak magnetic response and uncontrollable locomotion in high-rate blood flow, which hinder their practical applications. Here, we develop a fabrication method for three-dimensional (3D) hard magnetic microrobots (HM-microrobots) containing neodymium-iron-boron particles.

Mutations of the complex I PSST target gene confers acaricide resistance and a fitness cost in Panonychus citri.

Background: Pesticide resistance is a serious problem that threatens crop industries. Major resistance towards pyridaben, an acaricidal inhibitor of mitochondrial electron transport complex I (METI-Is), has been reported in tetranychids following its extensive use worldwide. Understanding mechanisms of pyridaben resistance is crucial for sustainable resistance management.

Mechanisms and engineering of a miniature type V-N CRISPR-Cas12 effector enzyme.

Type V CRISPR-Cas12 systems are highly diverse in their functionality and molecular compositions, including miniature Cas12f1 and Cas12n genome editors that provide advantages for efficient in vivo therapeutic delivery due to their small size. In contrast to Cas12f1 nucleases that utilize a homodimer structure for DNA targeting and cleavage with a preference for T- or C-rich PAMs, Cas12n nucleases are likely monomeric proteins and uniquely recognize rare A-rich PAMs. However, the molecular mechanisms behind RNA-guided genome targeting and cleavage by Cas12n remain unclear.

Association of lipid accumulation product with mortality in patients with diabetes mellitus.

Lipid accumulation product (LAP) is associated with increased risk of metabolic diseases and cardiovascular disease. However, its relationship with all-cause mortality and cardiovascular mortality among diabetes mellitus (DM) patients remains unclear. This study aims to explore the associations between LAP and mortality outcomes in patients with DM.

Enhancing 10-HDA production of by heterologous expression of MexHID transporter proteins.

10-Hydroxy-2-decenoic acid (10-HDA) is a medium-chain α,β-unsaturated carboxylic acid that exists in royal jelly with terminal hydroxylation. It has a broad market value because of its antibacterial, anti-inflammatory, anti-tumor, anti-radiation, and other active functions. The one-step whole-cell catalytic synthesis of 10-HDA by constructing engineered strains has improved the reaction rate to a certain extent compared with the previous two-step method.

Three typical organophosphorus flame retardants trigger thyroid hormone synthesis by inducing oxidative stress or inflammation reactions in Nthy-ori 3‑1 cells.

Accumulating evidence shows that organophosphorus flame retardants (OPFRs) can interfere with thyroid function in animals. However, studies on the effect of OPFR exposure on human thyroid hormone (TH) synthesis remain limited and controversial. In this study, we sought to investigate the effects and mechanisms of three typical OPFRs, including Tris (2-chloroethyl) phosphate (TCEP), tris (2-butoxyethyl) phosphate (TBEP), and triphenyl phosphate (TPHP), on TH synthesis using human thyroid follicular epithelial Nthy-ori 3-1 cells.

Early replacement of re-induction therapy following failed intensive induction treatment enhances the therapeutic efficacy of newly diagnosed AML.

20-30% of newly diagnosed Acute myeloid leukemia(AML) patients fail to achieve complete response (CR) following intensive induction chemotherapy. This retrospective study aimed to evaluate the efficacy of reinduction regimens in improving CR rates among newly diagnosed AML patients who did not achieve partial response(PR) after initial intensive induction therapy. We conducted a retrospective analysis of 175 newly diagnosed AML patients aged 18-60 years, treated at the First Affiliated Hospital of China Medical University between January 2020 and March 2024.

Gene network analysis reveals the responsive cascades of scallop (Patinopecten yessoensis) exposed to toxic Alexandrium catenella.

As filter-feeding bivalves, scallops exhibit remarkable tolerance to paralytic shellfish toxins (PSTs) produced by Alexandrium dinoflagellates, yet the molecular mechanisms enabling concurrent PST accumulation and physiological resilience remain poorly understood. Here, we integrated transcriptomics and weighted gene co-expression network analysis (WGCNA) to dissect dynamic gene networks in scallop digestive glands during a 15-day exposure to PST-producing algae. We identified eight responsive modules, with the hub module M4 coordinating all phases of xenobiotic metabolism: phase I oxidation (CYP enzymes), phase II conjugation (GST/GGT), and phase III efflux (MRP transporters).

All-Light Remote Driving and Programming of Soft Actuator Based on Selective Laser Stimulation and Modification.

Soft robots are advantageous due to their flexibility, ability to interact with humans, and multifunctional adaptability. However, developing soft robots that are unrestrained and can be reprogrammed for reversible control without causing damage remains a significant challenge. The majority of soft robots have a bilayer structure with internal stress, which limits their motion to pre-programmed anisotropic structures.

Long-Range Angular Correlations of Particle Displacements at a Plastic-to-Elastic Transition in Jammed Amorphous Solids.

Understanding how a fluid turns into an amorphous solid is a fundamental challenge in statistical physics, during which no apparent structural ordering appears. In the athermal limit, the two states are connected by a well-defined jamming transition, near which the solid is marginally stable. A recent mechanical response screening theory proposes an additional transition above jamming, called a plastic-to-elastic transition here, separating anomalous and quasielastic mechanical behavior.

Engineering eukaryotic transposon-encoded Fanzor2 system for genome editing in mammals.

Eukaryotic transposon-encoded Fanzor proteins hold great promise for genome-engineering applications as a result of their compact size and mechanistic resemblance to TnpB. However, the unmodified Fanzor systems show extremely low activity in mammalian cells. Guided by the predicted structure of a Fanzor2 complex using AlphaFold3, we engineered the NlovFz2 nuclease and its cognate ωRNA to create an evolved enNlovFz2 system, with an expanded target-adjacent motif (TAM) recognition scope (5'-NMYG) and a substantially improved genome-editing efficiency, achieving an 11.