TDT-MIL: a framework with a dual-channel spatial positional encoder for weakly-supervised whole slide image classification.

The classic multiple instance learning (MIL) paradigm is harnessed for weakly-supervised whole slide image (WSI) classification. The spatial position relationship located between positive tissues is crucial for this task due to the small percentage of these tissues in billions of pixels, which has been overlooked by most studies. Therefore, we propose a framework called TDT-MIL.

Advancing Cancer Immunotherapy through Engineering New PD-L1 Degraders: A Comprehensive Study from Small Molecules to PD-L1-Specific Peptide-Drug Conjugates.

Despite the considerable achievements of antibodies targeting PD-1/PD-L1 in cancer immunotherapy, limitations in antitumor immune response and pharmacokinetics hinder their clinical adoption. Small molecules toward PD-L1 degradation signifies an innovative avenue to modulate PD-1/PD-L1 axis. Herein, we unveil a comprehensive engineering involving the development of new PD-L1 degraders based on the berberine (BBR) and palmatine (PMT) bioactive frameworks and explore their translational potential for cancer immunotherapy using a peptide-drug conjugate strategy.

Reengineering of Donor-Acceptor-Donor Structured Near-Infrared II Aggregation-Induced Emission Luminogens for Starving-Photothermal Antitumor and Inhibition of Lung Metastasis.

Electron acceptor possessing strong electron-withdrawing ability and exceptional stability is crucial for developing donor-acceptor-donor (D-A-D) structured aggregation-induced emission luminogens (AIEgens) with second near-infrared (NIR-II) emission. Although 6,7-diphenyl-[1,2,5] thiadiazolo [3,4-] quinoxaline (PTQ) and benzobisthiadiazole (BBT) are widely employed as NIR-II building blocks, they still suffer from limited electron-withdrawing capacity or inadequate chemo-stability under alkaline conditions. Herein, a boron difluoride formazanate (BFF) acceptor is utilized to construct NIR-II AIEgen, which exhibits a better overall performance in terms of NIR-II emission and chemo-stability compared to the PTQ- and BBT-derived fluorophores.

Protein folding dependence on selenoprotein M contributes to steady cartilage extracellular matrix repressing ferroptosis via PERK/ATF4/CHAC1 axis.

Objective: Initiation of endoplasmic reticulum (ER) stress is pivotal to the advancement of osteoarthritis (OA). We aimed to explore the function of ER-resident selenoprotein M (SELM) in cartilage-forming chondrocytes, investigating how SELM participates in cartilage extracellular matrix (ECM) metabolism and ER stress modulation.

Methods: Articular cartilage samples with knee OA undergoing total knee arthroplasty were categorised into OA-smooth and OA-damaged groups, with primary chondrocytes extracted from smooth areas.

Ferroptosis and immunosenescence in colorectal cancer.

Colorectal cancer (CRC), ranked as the globe's third leading malignancy. Despite advancements in therapeutic approaches, the mortality rate remains distressingly high for those afflicted with advanced stages of the disease. Ferroptosis is a programmed form of cell death.

The spinal consequences of HT-2 toxin and selenium deficiency during bone maturation in mice.

In our investigation, we probed the ramifications of low selenium diets and HT-2 mycotoxin exposure on spinal development and structural fidelity in murine models. A cohort of 48 male mice was segregated into six groups: a control set, a singular low selenium diet group, two cohorts exposed to distinct concentrations of HT-2 toxin (1.6 and 3.

Graphdiyne as an emerging sensor platform: Principles, synthesis and application.

Background: Graphdiyne (GDY) is a kind of carbon material, which has highly delocalized π-conjugated system and feasible green synthesis. Nowadays, the use of GDY substrate as a sensing platform has become a new research hotspot and is rapidly developing. However, its application as a sensor is still relatively overlook compared to other fields.

Revolutionizing prognostic predictions in colorectal cancer: Macrophage‑driven transcriptional insights from single‑cell RNA sequencing and gene co‑expression network analysis.

Tumor-associated macrophages have become important biomarkers for cancer diagnosis, prognosis and therapy. The dynamic changes in macrophage subpopulations significantly impact the outcomes of cancer immunotherapy. Hence, identifying additional macrophage-related biomarkers is essential for enhancing prognostic predictions in colorectal cancer (CRC) immunotherapy.

A More Efficient and Safer Improved Percutaneous Pedicle Screw Insertion Technique-Trajectory Dynamic Adjustment Technique, Technical Note, and Clinical Efficacy.

Objective: Percutaneous pedicle screw fixation (PPSF) technique requires a very precise entry point of the Jamshidi needle, which leads to repeated adjustments, damaging the pedicle and increasing radiation exposure. This study was designed to propose an improved percutaneous pedicle screw fixation technique-trajectory dynamic adjustment (TDA) technique, and evaluate its feasibility and assess the clinical outcomes.

Method: A total of 445 patients with lumbar spondylolisthesis or lumbar spinal stenosis associated with instability from June 2017 to May 2022 were included in the retrospective study.

Kelp nanocellulose combined with fucoxanthin achieves lipid-lowering function by reducing oxidative stress with activation of Nrf2/HO-1/NQO1 pathway.

This study innovatively utilized kelp-derived nanocellulose and sodium caseinate (SC) to prepare fucoxanthin (Fx)-loaded nanoparticles, exploring their efficacy in reducing oxidative stress and inhibiting lipid accumulation. 2, 2, 6, 6-Tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation produced well-dispersed, kelp-derived nanocellulose. When these celluloses were mixed with SC at varying mass ratios, the composite nanoparticles showed excellent stability.

Inhalation of H/O (66.7 %/33.3 %) mitigates depression-like behaviors in diabetes mellitus complicated with depression mice via suppressing inflammation and preventing hippocampal damage.

Diabetes mellitus complicated with depression (DD) is a prevalent psychosomatic disorder. It is characterized by severe cognitive impairment, and associated with high rates of disability and mortality. Although conventional treatment options are available, the efficacy of these regimens in managing DD remains limited.

Achieving automated and high-precision in situ analysis of the dimensional accuracy and dynamic deformation of 3D-printed surgical templates: an in vitro study.

Purpose: To demonstrate the viability of a coordinate-measuring machine (CMM) for the geometric analysis of 3D printed surgical templates.

Methods: The template was designed and modified by adding 18 cylindrical landmarks for CMM test and then classified into five groups according to the slicing software and resins (opaque and transparent): Streamflow-O, Streamflow-T, Shapeware-T, Rayware-T and Polydevs-T (N = 3). Three standing times (0 w, 1 w, and 2 w) were included to observe possible deformation.

The role of SIRT1 in autophagy and drug resistance: unveiling new targets and potential biomarkers in cancer therapy.

Cancer, the world's second leading cause of death after cardiovascular diseases, is characterized by hallmarks such as uncontrolled cell growth, metastasis, angiogenesis, hypoxia, and resistance to therapy. Autophagy, a cellular process that can both support and inhibit cancer progression, plays a critical role in cancer development and progression. This process involves the formation of autophagosomes that ultimately fuse with lysosomes to degrade cellular components.

BAFF overexpression in triple-negative breast cancer promotes tumor growth by inducing IL-10-secreting regulatory B cells that suppress anti-tumor T cell responses.

Purpose: Despite BAFF's (B cell activating factor, BAFF) known influence on B cell survival and proliferation, its specific effects within the tumor microenvironment remain unclear. We aimed to elucidate how BAFF overexpression in breast cancer cells impacts tumor growth and the functions of T and B cells in the tumor microenvironment.

Methods: BAFF was overexpressed in the 4T1 mouse triple-negative breast cancer cell line, and tumor growth, immune cell infiltration, and activity were assessed in vitro and in vivo using flow cytometry, co-culture assays, and mouse tumor models with B cell depletion.

microRNA-2117 Negatively Regulates Liver Cancer Stem Cells Expansion and Chemoresistance Via Targeting SOX2.

Cancer stem cells (CSCs) are involved in the regulation of tumor initiation, progression, recurrence, and chemoresistance. However, the role of microRNAs (miRNAs) in liver CSCs has not been fully understood. Here we show that miR-2117 is downregulated in liver CSCs and predicts the poor prognosis of hepatocellular carcinoma (HCC) patients.

G protein coupled receptor in apoptosis and apoptotic cell clearance.

Apoptosis is a genetically programmed form of cell death that is substantially conserved across the evolutionary tree. Apoptotic cell elimination includes recognition, phagocytosis, and degradation. Failure to clear apoptotic cells can ultimately cause a series of human diseases, such as systemic lupus erythematosus, Alzheimer's disease, atherosclerosis, and cancer.

Oral Microbiota Variations in Psoriasis Patients Without Comorbidity.

Background: Psoriasis is a chronic inflammatory skin disease, and its etiology is still unclear. There is increasing evidence suggesting that microorganisms may trigger psoriasis. However, the relationship between psoriasis and oral microbiota remains poorly understood.

Radiomics Biomarkers to Predict Checkpoint Inhibitor Pneumonitis in Non-small Cell Lung Cancer.

Rationale And Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). However, immune-related adverse events still occur, of which checkpoint inhibitor pneumonitis (CIP) is the most common. We aimed to construct and validate a contrast-enhanced computed tomography-based radiomic nomogram to predict the probability of CIP before ICIs treatment in NSCLC.

C-Reactive Protein Induces Immunosuppression by Activating FcγR2B in Pulmonary Macrophages to Promote Lung Metastasis.

C-reactive protein (CRP) is a liver-derived acute phase reactant that is a clinical marker of inflammation associated with poor cancer prognosis. Elevated CRP levels are observed in many types of cancer and are associated with significantly increased risk of metastasis, suggesting that CRP could have prometastatic actions. In this study, we reported that CRP promotes lung metastasis by dampening the anticancer capacity of pulmonary macrophages in breast cancer and melanoma.