A combined enteric neuron-gastric tumor organoid reveals metabolic vulnerabilities in gastric cancer.

The discrepancy between organoid and immortalized cell line cultures for cancer target discovery remains unclear. Here, our multi-tiered clustered regularly interspaced short palindromic repeats (CRISPR) screens reveal in vivo-relevant metabolic dependencies and synthetic lethal pairs that can be uncovered with tumor organoids but not cell lines or even three-dimensional (3D) spheroids. These screens identify lanosterol synthase and acetyl-coenzyme A (CoA) carboxylase inhibitors as effective treatments that impede xenografted tumor growth in mice.

Platelet-rich plasma enhances local homing of umbilical cord-derived mesenchymal stem cells to articular cartilage by increasing the quantity and activation of integrin ꞵ1.

Background: Enhancing mesenchymal stem cells (MSCs) engraftment at the degenerative cartilage is important to increase the therapeutic effect of cartilage regeneration. Platelet-rich plasma (PRP) is known to have anti-inflammatory and anabolic effects for the treatment of osteoarthritis and has been reported to be commonly used with MSCs. However, little is known about the effects of PRP on MSCs adhesion to cartilage extracellular matrix (ECM).

Dual probe ligation in situ hybridization with rolling-circle amplification for high-plex spatial transcriptomics.

New biological insights are increasingly dependent upon a deeper understanding of tissue architectures. Critical to such studies are spatial transcriptomics technologies, especially those amenable to analysis of the most widely available human tissue type, formalin-fixed and paraffin-embedded (FFPE) clinical specimens. Here we build on our previous oligonucleotide probe ligation-based approach to accurately analyze FFPE mRNA, which suffers from variable levels of degradation.

International Trends in Opioid Prescribing by Age and Sex from 2001 to 2019: An Observational Study Using Population-Based Databases from 18 Countries and One Special Administrative Region.

Objective: To characterize multinational trends and patterns of opioid analgesic prescribing by sex and age.

Design, Setting, And Participants: We studied opioid analgesic prescribing from 2001 to 2019 with common protocol using population-based databases from eighteen countries and one special administrative region.

Main Outcome Measures: We measured opioid prescribing by geographical region, sex and age, estimating annual prevalent, incident, and nonincident opioid prescribing per 100 population with a 95% confidence interval (CI) and meta-analyzed the multinational and regional opioid prescribing with a random-effects model.

Post-functionalization of polyethers by photoinduced C-H amidation via polar-radical relay.

The C-H functionalization of polymers enables the direct incorporation of new functional groups into polymer backbones, presenting significant opportunities for the upcycling of commodity polymers. However, developing reactions that achieve selective functionalization while preserving the intrinsic features of polymers and avoiding undesirable structure deformation remains a considerable challenge. In this study, we present a transition metal-free post-functionalization approach for polyethers via a photoinduced α-C-H amidation reaction.

High-Quality Targeted Temperature Management After Cardiac Arrest; Results from the Korean Hypothermia Network Prospective Registry.

Most out-of-hospital cardiac arrest (OHCA) survivors are comatose due to hypoxic ischemic brain injury. Targeted temperature management (TTM) is the only evidence-based neuroprotective intervention for this condition; however, the optimal implementation of TTM has yet to be determined. The concept of high-quality TTM has been proposed to improve patient outcomes, but its clinical impact has not been thoroughly evaluated.

Synergistic Anti-Obesity Effects of Q180 and (CKDB-322) in High-Fat-Diet-Induced Obese Mice.

Obesity and associated metabolic disorders are rising globally, necessitating effective dietary strategies. CKDB-322, a formulation containing Q180 and , was evaluated for anti-obesity efficacy using in vitro adipocyte differentiation and in vivo high-fat-diet (HFD)-induced obese mouse models. In 3T3-L1 cells, CKDB-322 suppressed adipogenesis by downregulating PPARγ and C/EBPα and enhancing glycerol release.

Risks of prematurity and low birth weight associated with trimester-specific prenatal benzodiazepine exposure.

Background: Intrauterine exposure of the developing fetus or neonate to bendodiazepine may lead to fetal abnormalities or adverse reactions. We sought to investigate whether benzodiazepine use before or during different trimesters of pregnancy had different associations with incident preterm births (PTB) or small for gestational age (SGA) infants.

Methods: We conducted a 13-year longitudinal cohort study incorporating population-wide, sibling, and paternal comparisons.

The impact of social determinants of health on outcomes of brexucabtagene autoleucel in adults with relapsed/refractory B-cell acute lymphoblastic leukemia.

Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T (CAR T) cell therapy approved for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We studied the impact of social determinants of health (SDoH) on outcomes of adults with B-ALL receiving brexu-cel. This retrospective analysis included adults (≥18 years) with R/R B-ALL treated with brexu-cel between 2021 and 2023.

Cholesterol-modulating effects of Korean red ginseng (KRG) targeting PCSK9 in hyperlipidemia.

Hyperlipidemia represents a major global health concern, closely linked to cardiovascular disease (CVD) and metabolic syndrome. Effective regulation of blood lipid and cholesterol (CHO) is essential for preventing and managing this condition. Korean red ginseng (KRG), a traditional medicinal plant, exhibits diverse pharmacological properties, including antihyperlipidemic, immune-enhancing, anti-fatigue, and antistress effects.

Agreement Between Different Types of Blood Pressure Monitoring : A Systematic Review and Network Meta-analysis.

Background: Accurate blood pressure measurement (BPM) is essential for managing hypertension, but previous studies have not systematically compared different monitoring methods across varying BP levels. To address this gap, a comprehensive analysis using network meta-analysis (NMA) and meta-regression was done to evaluate their agreement and clinical implications.

Purpose: To compare BP values obtained using different BPM methods using office BPM (OBPM) as the reference.

Site-Selective Electrochemical Intramolecular C(sp)-H Selenylation for Dibenzoselenophene Synthesis.

We report a robust and eco-conscious electrosynthetic protocol for efficiently constructing structurally diverse and biologically relevant dibenzoselenophenes. This transformation proceeds electrochemical intramolecular C-H activation of bis(biaryl) diselenides, employing LiClO as a green electrolyte and tetrabutylammonium bromide as an additive, conducted in DMSO at 70 °C under a constant current of 10 mA using Pt/Pt electrodes. The newly developed method offers several notable advantages, including mild and energy-efficient conditions, transition-metal-free catalysis, short reaction times, high to excellent yields, broad substrate tolerance, scalability to gram-scale synthesis, operational simplicity, and environmental friendliness.

Improved clinical outcomes with a modified warming protocol in donor oocyte cycles.

Background: Recent studies have attempted to improve laboratory efficiency while preserving clinical outcomes by shortening the time to warm cryopreserved embryos, though it is still unclear for oocytes. This study thus aimed to evaluate the effects of a modified warming protocol (MWP) on embryonic development and pregnancy outcomes of vitrified donor oocytes.

Methods: The data of this retrospective cohort study were collected from women who underwent donor cycles (fresh or vitrified oocytes) at Lee Women's Hospital, Taiwan, from January 2019 to August 2024.

Lymphodepletion, tumor-infiltrating lymphocytes, and high versus low dose IL-2 followed by pembrolizumab in patients with metastatic melanoma.

This study evaluated the efficacy and safety of unengineered tumor-infiltrating lymphocytes (TILs) combined with pembrolizumab and either high (HD, Arm-1) or low (LD, Arm-2) doses of IL-2 in patients with metastatic melanoma (MM). Patients were lymphodepleted with cyclophosphamide and fludarabine, followed by TIL infusion and IL-2 (Arm-1: 720,000 IU/kg IV q 8 hrs up to 15 doses; Arm-2: 2 million IU SC for 14 days). Patients received pembrolizumab 200 mg IV starting 21 days post-TIL infusion, and every 3 weeks for up to 2 years.

Discovery of asymmetric pyridinium-based fluorescent probes with large Stokes shifts for live neural stem/progenitor cells.

Fluorescent dyes are widely used in biological systems, yet the number of fluorescent scaffolds with desirable photophysical properties remains limited. Herein, we report the synthesis of novel asymmetric pyridinium salts facile Rh(III) C-H activation. A structure-activity relationship (SAR) study led to the identification of a lead candidate, KD01, which exhibits a large Stokes shift (Ex/Em = 405/605 nm) and bright fluorescence only upon interaction with live brain cells.

Comparison of Clinical Characteristics in Older-Onset and Common-Age-of-Onset Gout: A Prospective Gout Cohort Study.

Objectives: Gout is an inflammatory arthritis caused by monosodium urate crystal deposition in the joints. Its clinical presentation varies by age of onset. This study compared the clinical features and treatment patterns of older-onset gout and common-age-of-onset gout.

Recurrent connectivity supports carbon dioxide sensitivity in mosquitoes.

The mosquito 's human host-seeking behavior depends on the integration of multiple sensory cues. One of these cues, carbon dioxide (CO), gates odorant and heat pathways and activates host-seeking behavior. The neuronal circuits underlying processing of CO information remain unclear.

Single-Flask Manganese(I)-Catalyzed Dienylation and Diels-Alder Cascade: Synthesis of Indole-Cyclohexene Hybrids with Anti-Inflammatory Activity.

A manganese(I)-catalyzed C-H dienylation of indoles with allenyl benzoate was developed that enables access to C2-dienylated indoles. Moreover, a one-pot consecutive cycloaddition process using a range of dienophiles afforded a series of complex alicyclic scaffolds. Mechanistic experiments demonstrated reversible C-H metalation and a possible five-membered manganacycle intermediate.

The Growth Mechanism of Boron-Doped Diamond in Relation to the Carbon-to-Hydrogen Ratio Using the Hot-Filament Chemical Vapor Deposition Method.

This study synthesized boron-doped diamond (BDD) thin films using hot-filament chemical vapor deposition at different carbon-to-hydrogen (C/H) ratios in the range of 0.3-0.9%.

In vivo efficacy of NRL knockdown with cell-penetrating siRNA in retinal degeneration.

Retinal degenerative diseases, such as retinitis pigmentosa (RP) and age‑related macular degeneration (AMD), lead to progressive vision loss through photoreceptor degeneration; RP begins with the gradual loss of peripheral rods, whereas AMD causes central‑vision loss mainly because macular cones and parafoveal rods degenerate. The neural retina leucine zipper (NRL) directs rod photoreceptor differentiation, and its disruption has been linked to upregulated cone-specific markers in rods. This study investigates the therapeutic potential of a cell-penetrating asymmetric small interfering RNA targeting NRL (cp-asiNRL) to induce rod-to-cone conversion and mitigate retinal degeneration.

Synthesis of γ-Carbolines through Annulative Cyclization between Indolyl Azines and Alkynes under Rhodium Catalysis.

Functionalized carbolines play a crucial role in the discovery of bioactive compounds and functional materials. In this study, we report a Rh(III)-catalyzed annulative synthesis of γ-carbolines from indolyl azines and internal alkynes. Remarkably, indolyl azines can undergo N-N bond cleavage under the influence of a Rh(III) catalyst, yielding 2-fold ketimines, which demonstrates the atom economy of indolyl azines in catalytic C-H functionalizations.

Sensitization of tumours to immunotherapy by boosting early type-I interferon responses enables epitope spreading.

The success of cancer immunotherapies is predicated on the targeting of highly expressed neoepitopes, which preferentially favours malignancies with high mutational burden. Here we show that early responses by type-I interferons mediate the success of immune checkpoint inhibitors as well as epitope spreading in poorly immunogenic tumours and that these interferon responses can be enhanced via systemic administration of lipid particles loaded with RNA coding for tumour-unspecific antigens. In mice, the immune responses of tumours sensitive to checkpoint inhibitors were transferable to resistant tumours and resulted in heightened immunity with antigenic spreading that protected the animals from tumour rechallenge.

Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.

Background: Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis.

Results: We identify 13 loci with cross-population associations including known loci at/near CR1, BIN1, TREM2, CD2AP, PTK2B, CLU, SHARPIN, MS4A6A, PICALM, ABCA7, APOE, and two novel loci not previously reported at 11p12 (LRRC4C) and 12q24.

Exploring the link between grit and excessive daytime sleepiness: a study in a population sample.

Purpose: Excessive daytime sleepiness (EDS) is a common condition with implications for individual health and public safety. While factors such as snoring and depression are known contributors to EDS, the role of grit in EDS remains unexplored. This study aimed to investigate the association between and EDS in a representative sample of Korean adults, with a specific focus on the two components of grit: perseverance of effort (PE) and consistency of interest (CI).