Unveiling the shared genetic architecture between testosterone and polycystic ovary syndrome.

Testosterone (T) is a critical predictor of polycystic ovary syndrome (PCOS) but the genetic overlap between T and PCOS has not been established. Here by leveraging genetic datasets from large-scale genome-wide association studies, we assessed the genetic correlation and polygenic overlap between PCOS and three T-related traits using linkage disequilibrium score regression and the bivariate causal mixture model methods. The conjunctional false discovery rate (conjFDR) method was employed to identify shared causal variants.

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.

Preoperative Glycosylated Hemoglobin A1C Impacts Long-Term Outcomes Following Curative-Intent Resection of Nonfunctional Gastroenteropancreatic Neuroendocrine Tumors.

Background: To investigate the impact of preoperative glycosylated hemoglobin A1C (HbA1c) among patients following curative-intent resection of nonfunctional gastroentropancreatic neuroendocrine tumors (GEP-NETs).

Methods: Patients who underwent curative-intent resection for GEP-NETs from 2000 to 2020 were identified from the US Neuroendocrine Tumor Study Group (US-NETSG). Preoperative blood HbA1c levels were defined as high HbA1c (≥ 6.

Therapeutic Suppression of Atherosclerotic Burden and Vulnerability via Inhibition in Plaque Macrophages Using Dual-Targeted Liposomes.

Atherosclerosis, characterized by chronic inflammation within the arterial wall, remains a pivotal concern in cardiovascular health. We developed a dual-targeted liposomal system encapsulating Dll4-targeting siRNA, designed to selectively bind to pro-inflammatory M1 macrophages through surface conjugation with anti-F4/80 and anti-CD68 antibodies. The Dll4-targeting siRNA is then delivered to the macrophages, where it silences Dll4 expression, inhibiting Notch signaling and reducing plaque vulnerability.

Exosomes from adipose-derived stem cells overexpressing microRNA-671-3p promote fat graft angiogenesis and adipogenic differentiation.

Exosomes from adipose-derived stem cells (ADSCs) have been demonstrated to benefit angiogenesis, wound healing, and fat grafting. Small noncoding RNAs such as microRNA (miRNA) and circular RNA play critical roles in mediating the function of ADSCs-derived exosomes. However, the underlying mechanisms have not been fully elucidated.

Methionine restriction alleviates diabetes-associated cognitive impairment via activation of FGF21.

Glucose metabolism disturbances may result in diabetes-associated cognitive decline (DACI). Methionine restriction (MR) diet has emerged as a potential dietary strategy for managing glucose homeostasis. However, the effects and underlying mechanisms of MR on DACI have not been fully elucidated.

Pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer and brain metastases (PERMEATE trial): overall survival results from a multicenter, single-arm, two-cohort, phase 2 trial.

Background: The phase 2 PERMEATE study has shown the antitumor activity and safety of pyrotinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and brain metastases. In this report, survival results were updated with extended follow-up.

Methods: Between January 29, 2019 and July 10, 2020, adult patients with HER2-positive metastatic breast cancer who had radiotherapy-naïve brain metastases (cohort A, n = 59) or progressive disease after radiotherapy (cohort B, n = 19) were enrolled and received pyrotinib (400 mg once daily) and capecitabine (1000 mg/m twice daily on days 1-14 of each 21-day cycle) until disease progression or unacceptable toxicity.

Design and synthesis of triazolopyridine derivatives as potent JAK/HDAC dual inhibitors with broad-spectrum antiproliferative activity.

A series of triazolopyridine-based dual JAK/HDAC inhibitors were rationally designed and synthesised by merging different pharmacophores into one molecule. All triazolopyridine derivatives exhibited potent inhibitory activities against both targets and the best compound 4-(((5-(benzo[][1, ]dioxol-5-yl)-[1, 2, 4]triazolo[1, 5-]pyridin-2-yl)amino)methyl)--hydroxybenzamide (19) was dug out. 19 was proved to be a pan-HDAC and JAK1/2 dual inhibitor and displayed high cytotoxicity against two cancer cell lines MDA-MB-231 and RPMI-8226 with IC values in submicromolar range.

Dual Orthogonally Polarized Lasing Assisted by Imaginary Fermi Arcs in Organic Microcavities.

The polarization control of micro- and nanolasers is an important topic in nanophotonics. Up to now, the simultaneous generation of two distinguishable orthogonally polarized lasing modes from a single organic microlaser remains a critical challenge. Here, we demonstrate simultaneously orthogonally polarized dual lasing from a microcavity filled with an organic single crystal exhibiting selective strong coupling.

Acellular dermal matrix hydrogels promote healing of radiation-induced skin injury in a rat model.

Background: radiation-induced skin injury (RISI) is a common complication of radiotherapy, affecting 85-95% of patients. Current treatments lack sufficient evidence of efficacy. Acellular dermal matrix (ADM) hydrogels have shown promise in treating chronic wounds, burns, and ulcers, but their potential in RISI remains unexplored.

Transforming growth factor-β (TGF-β) signaling pathway-related genes in predicting the prognosis of colon cancer and guiding immunotherapy.

Background: Colon cancer is a malignant tumor with high malignancy and a low survival rate whose heterogeneity limits systemic immunotherapy. Transforming growth factor-β (TGF-β) signaling pathway-related genes are associated with multiple tumors, but their role in prognosis prediction and tumor microenvironment (TME) regulation in colon cancer is poorly understood. Using bioinformatics, this study aimed to construct a risk prediction signature for colon cancer, which may provide a means for developing new effective treatment strategies.

Systematic optimization of UCNPs-LFA for Helicobacter pylori nucleic acid detection at point-of-care.

Helicobacter pylori (Hp) prevail globally as the primary cause of gastritis, gastric ulcer, and potential gastric cancer, highlighting the need for rapid and precise point-of-care (POC) detection of Hp nucleic acid. Upconversion nanoparticle-based lateral flow assay (UCNPs-LFA) exhibit great potential in POC detection, due to their high optical stability and absence of background fluorescence. However, insufficient sensitivity for nucleic acid detection remains a key challenge.