Mechanistic roles of long non-coding RNAs in DNA damage response and genome stability.

To maintain genomic stability, cells have evolved complex mechanisms collectively known as the DNA damage response (DDR), which includes DNA repair, cell cycle checkpoints, apoptosis, and gene expression regulation. Recent studies have revealed that long non-coding RNAs (lncRNAs) are pivotal regulators of the DDR. Beyond their established roles in recruiting repair proteins and modulating gene expression, emerging evidence highlights two particularly intriguing functions.

A Rare Case: Composite Paraganglioma-Ganglioneuroma in a Neurofibromatosis 1 Patient and Literature Review.

Background: Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-secreting neuroendocrine tumors originating from the embryonic neural crest. Approximately 30% of PPGLs are hereditary and are frequently associated with genetic syndromes, including neurofibromatosis type 1 (NF1). Composite PPGLs, which include components of both PPGLs and related tumors such as ganglioneuromas, are extremely rare in NF1 patients.

Comparative effectiveness and safety of second-line therapies and dosing regimens for advanced hepatocellular carcinoma: a network meta-analysis.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated death globally. Second-line therapies are crucial for improving survival and quality of life among individuals suffering from advanced HCC who have not responded to first-line therapies. This study sought to evaluate the safety and efficacy of different second-line therapies for advanced HCC by network meta-analysis.

Discovery of -(thiazol-2-yl) Furanamide Derivatives as Potent Orally Efficacious AR Antagonists with Low BBB Permeability.

Resistance-conferring mutations in the androgen receptor (AR) ligand-binding pocket (LBP) compromise the effectiveness of clinically approved orthosteric AR antagonists. Targeting the dimerization interface pocket (DIP) of AR presents a promising therapeutic approach. In this study, we report the design and optimization of -(thiazol-2-yl) furanamide derivatives as novel AR DIP antagonists, among which was the most promising candidate.

Observing a robot peer's failures facilitates students' classroom learning.

According to productive failure (PF) theory, experiencing failure during problem-solving can enhance students' knowledge acquisition in subsequent instruction. However, challenging students with problems beyond their current capabilities may strain their skills, prior knowledge, and emotional well-being. To address this, we designed a social robot-assisted teaching activity in which students observed a robot's unsuccessful problem-solving attempts, offering a PF-like preparatory effect without requiring direct failure.

Modulating Molecular Microheterogeneity within Electrolytes Controls Macroscopic Battery Performance.

Narrow electrochemical windows and high reactivity of aqueous solutions remain critical bottlenecks for the practical application of aqueous batteries. However, the mechanisms for tuning microscopic reactivity of HO molecules in aqueous electrolytes remain elusive. This study employs six ether molecules with distinct structures and solvation powers to regulate the microstructure of aqueous solutions.

A randomized, double-blind, placebo-controlled phase 1 trial of the topical pan-lysyl oxidase inhibitor PXS-6302 in mature scars.

Skin scars remain a substantial clinical challenge because of their impact on appearance and psychological well-being. Lysyl oxidases catalyze collagen cross-linking, a key factor in scar development. Here, we report a randomized, double-blind, placebo-controlled phase 1 study to assess the safety and tolerability of PXS-6302, a topical pan-lysyl oxidase inhibitor, in treating mature scars (ACTRN12621001545853).

Evidence for Similar Collectivity of High Transverse-Momentum Particles in p-Pb and Pb-Pb Collisions.

Charged hadron elliptic anisotropies (v_{2}) are presented over a wide transverse momentum (p_{T}) range for proton-lead (pPb) and lead-lead (PbPb) collisions at nucleon-nucleon center-of-mass energies of 8.16 and 5.02 TeV, respectively.

Observation of Three Resonant Structures in the Cross Section of e^{+}e^{-}→π^{+}π^{-}h_{c}.

Using e^{+}e^{-} collision data collected with the BESIII detector operating at the Beijing electron positron collider, the cross section of e^{+}e^{-}→π^{+}π^{-}h_{c} is measured at 59 points with center-of-mass energy sqrt[s] ranging from 4.009 to 4.950 GeV with a total integrated luminosity of 22.

Onset of Constituent Quark Number Scaling in Heavy-Ion Collisions at RHIC.

Partonic collectivity is one of the necessary signatures for the formation of quark-gluon plasma in high-energy nuclear collisions. Number of constituent quarks (NCQ) scaling has been observed for hadron elliptic flow v_{2} in top energy nuclear collisions at the Relativistic Heavy Ion Collider and the LHC, and this has been theoretically suggested as strong evidence for partonic collectivity. In this Letter, a systematic analysis of v_{2} of π^{±}, K^{±}, K_{S}^{0}, p, and Λ in Au+Au collisions at sqrt[s_{NN}]=3.

Integrating population-level and cell-based signatures for drug repositioning.

Motivation: Drug repositioning presents a streamlined and cost-efficient way to expand the range of therapeutic possibilities. Drugs with human genetic evidence are more likely to advance successfully through clinical trials towards FDA approval. Single gene-based drug repositioning methods have been implemented, but approaches leveraging a broad spectrum of molecular signatures remain underexplored.

Global, regional, and national burdens of five main digestive system cancers in adolescents and young adults from 1990 to 2021 based on the Global Burden of Disease Study 2021: A cross-sectional study.

Objective: To evaluate the burden and trends of digestive system cancers in adolescents and young adults (AYAs) globally between 1990 and 2021.

Methods: Data were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (1990-2021). We analyzed global, regional, and national disease burdens by calculating the age-standardized incidence (ASIR), mortality (ASMR), and disability-adjusted life years (DALYs) for AYAs.

Systemic Delivery of an mRNA-Encoding, Tumor-Activated Interleukin-12 Lock to Eliminate Tumors and Avoid Immune-Related Adverse Events.

Interleukin-12 (IL-12) is a robust proinflammatory cytokine that activates immune cells, such as T cells and natural killer cells, to induce antitumor immunity. However, the clinical application of recombinant IL-12 has been limited by systemic immune-related adverse events (irAEs) and rapid degradation. To address these challenges, we employed mRNA technology to encode a tumor-activated IL-12 "lock" fusion protein that offers both therapeutic efficacy and systemic safety.

ANK3 as a Novel Genetic Biomarker for Liafensine in Treatment-Resistant Depression: The ENLIGHTEN Randomized Clinical Trial.

Importance: This study represents a first successful use of a genetic biomarker to select potential responders in a prospective study in psychiatry. Liafensine, a triple reuptake inhibitor, may become a new precision medicine for treatment-resistant depression (TRD), a major unmet medical need.

Objective: To determine whether ANK3-positive patients with TRD benefit from a 1-mg and/or 2-mg daily oral dose of liafensine, compared with placebo, in a clinical trial.

Efficacy of levocarnitine combined with tadalafil in treating oligozoospermia and asthenozoospermia: effects on serum sex hormones and sexual function.

Objective: This study aimed to evaluate the efficacy of combining levocarnitine with tadalafil in treating oligozoospermia and asthenozoospermia and to analyze its effects on serum sex hormone levels and sexual function.

Methods: A total of 80 patients diagnosed with oligozoospermia or asthenozoospermia at our hospital between March 2023 and February 2024 were randomly divided into two groups, A and B, with 40 patients each. Group A received levocarnitine combined with tadalafil, while Group B was administered levocarnitine alone.

The effect of CD40 agonist antibody therapy on the pancreatic cancer microenvironment.

The fourth leading cause of cancer-related fatalities in the USA is pancreatic ductal adenocarcinoma (PDAC), a particularly deadly illness that is resistant to immunotherapy. One of the Main Obstacles in cancer research is developing better treatments for PDAC, which has the lowest 5-year survival rate of any malignancy. Anti-CTLA-4, anti-PD-L1, and anti-PD-1 immune checkpoint blockade medications also have poor results in these patients, which may indicate the presence of other immunosuppressive mechanisms in the pancreatic tumor microenvironment (TME).

Tetrandrine has protective role in myocardial ischemia/reperfusion injury via the TRPV2/Ca/calcineurin/NFAT axis.

Background: The protective function of the tetrandrine (TET)-mediated transient receptor potential vanilloid 2 (TRPV2) channel in myocardial ischemia/reperfusion injury (MI/RI) has been established in numerous investigations. The objective of the current study was to explain how TRPV2 further modulates downstream factors to influence the progression of MI/RI.

Methods: To this end, an MI/RI model in rats and a hypoxia-reoxygenation (H/R) cell model in H9c2 cells were constructed.

Bio-Scaffold Developed With Decellularized Human Amniotic Membrane Composite 3D Umbilical Cord Mesenchymal Stem Cell Spheroids Accelerate the Repair of Rat Defective Wounds.

Defective wounds pose health risks, and treatment is challenging. Umbilical cord-derived mesenchymal stem cells (UCMSCs) show promise for healing. Primary UCMSCs were isolated and extracted in vitro, and the proliferation and differentiation characteristics were detected by flow cytometry and trilineage differentiation, and a 3D spherical cell culture was performed.

Expert consensus regarding the clinical application of liver contrast-enhanced US with Sonazoid (Sonazoid CEUS).

Sonazoid, a combined blood pool and Kupffer-cell agent, can be specifically phagocytosed by Kupffer cells in the liver, allowing lesion detection and characterization of focal liver lesions (FLLs) at the post-vascular phase apart from the vascular phase which is similar to that of other second-generation US contrast agents. Sonazoid CEUS is currently approved for use in some Asian countries. With the increasing use of Sonazoid CEUS for FLLs in clinical practice, developing consensus or guidelines to help standardize its use is required.

Unveiling the roles of PEX16 in female reproductive capacity and lifespan of brown planthopper, Nilaparvata lugens (Stål), in relation to PEX14.

Background: Peroxisomes are essential for the metabolism of very long-chain fatty acids (VLCFAs). Their biogenesis requires peroxins encoded by the PEX genes. While the significance of PEX14 has been established in the major rice pest the brown planthopper (Nilaparvata lugens), the role of PEX16 as a peroxisome biogenesis initiator remains uncharacterized in this pest.

Dual-arterial occlusion of the celiac trunk and superior mesenteric artery for laparoscopic enucleation of deep-seated or broad-based pancreatic head tumors: a prospective, single-arm pilot study.

Background: Enucleation has the advantages of preserving function and avoiding pancreaticoduodenectomy for benign and low-grade malignant neoplasms in the pancreatic head. However, laparoscopic enucleation (LEn) of pancreatic head tumors remains challenging in terms of bleeding control and duct integrity preservation because of the complicated blood supply to the pancreatic head and the adjacent relationships of lesions with the main pancreatic duct (MPD), especially for deep-seated or broad-based lesions. Here, we developed a novel dual-arterial occlusion technique to facilitate LEn of pancreatic head tumors and evaluated its feasibility and safety.