p53 inhibits OTUD5 transcription to promote GPX4 degradation and induce ferroptosis in gastric cancer.

Background: Gastric cancer is one of the most prevalent malignant tumors within the digestive system, and ferroptosis playing a crucial role in its progression. Glutathione peroxidase 4 (GPX4), a key negative regulator of ferroptosis, is highly expressed in gastric cancer and contributes to tumor growth. Targeting the regulation of GPX4 has emerged as a promising approach to induce ferroptosis and develop effective therapy for gastric cancer.

Injectable visible light cross-linking aldehyde-based methacrylated hyaluronic acid hydrogels enhance cartilage repair via improved BMSC homing and chondrogenic differentiation.

Self-repair of articular cartilage defects is a significant challenge that can be addressed using drug-infused hydrogels, which improve injection convenience and provide immediate in situ adhesion. In this study, we developed a hydrogel incorporating Lipo@Kartogenin (KGN) and the cationic functional peptide SKPPGTSS (SKP) linked to aldehyde-based methacrylated hyaluronic acid (AHAMA). The innovative injectable hydrogel responded to visible light, allowing cross-linking under white light (∼30 s) and effective adhesion to cartilage tissue.

Investigating the controversy surrounding statin therapy and Achilles tendinopathy using Mendelian randomization analysis.

Background: The relationship between statin therapy and tendon injuries, particularly Achilles tendinopathy, which is the body's largest and strongest tendon, remains controversial.

Aim: This study employed Mendelian Randomization (MR) analysis to explore the causal link between statin therapy and Achilles tendinopathy (ATP).

Method: Summary statistics were obtained from genome-wide association studies on statin medication and four specific statin drugs from public databases, as well as data related to two ATP phenotypes, namely Achilles tendinitis and Achilles tendon injury.

Centromere protein U mediates the ubiquitination and degradation of RPS3 to facilitate temozolomide resistance in glioblastoma.

Aims: Temozolomide (TMZ) is the first-line chemotherapeutic agent for glioblastoma (GBM) therapy; however, resistance to TMZ remains a major obstacle in GBM treatment. The aim of this study is to elucidate the mechanisms underlying TMZ resistance and explore how to enhance the sensitivity of GBM to TMZ.

Methods: GBM organoids were generated from patient samples, and organoid-based TMZ sensitivity testing was performed.

Exploring the Diet-diverticular Disease Link: Insights from a Comprehensive Mendelian Randomization Study.

Background: The interplay between dietary habits and the development of Diverticular Disease (DD) has long been a subject of vibrant debate.

Objective: Utilizing Mendelian Randomization (MR), this study aims to meticulously examine the causal dynamics at play.

Methods: The foundation for the Genome-Wide Association Studies (GWAS) on DD was established using a dataset from the FinnGen consortium, encompassing 33,619 patients and 329,381 control participants.

Adaptive Plasticity Tumor Cells Modulate MAPK-Targeting Therapy Response in Colorectal Cancer.

MAPK pathway inhibitors (MAPKi) are increasingly used in the treatment of advanced colorectal cancer, but often produce short-lived responses in patients. Although acquired resistance by mutations in tumors have been found to reduce response in some patients, additional mechanisms underlying the limited response durability of MAPK targeting therapy remain unknown. Here, we denote new contributory tumor biology and provide insight on the impact of tumor plasticity on therapy response.

Symptom Network and Subgroup Analysis in Patients with Exacerbation of Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.

Purpose: This study aims to construct a contemporaneous symptom network of inpatients with Exacerbation of Chronic Obstructive Pulmonary Disease (ECOPD) based on the symptom cluster, identify core and bridge symptoms, and patient subgroups with different symptom clusters based on individual differences in the intensity of patient symptom experiences.

Patients And Methods: This study used convenience sampling to collect demographic, symptom, auxiliary examination, and prognosis information of 208 inpatients with ECOPD from April 2022 to October 2023. The data underwent exploratory factor analysis (EFA), symptom network analysis, latent class analysis (LCA), Spearman correlation analysis, Wilcoxon signed-rank test, single-factor regression and multiple-factor stepwise regression.

Observation of Extraordinary Vibration Scatterings Induced by Strong Anharmonicity in Lead-Free Halide Double Perovskites.

Lead-free halide double perovskites provide a promising solution for the long-standing issues of lead-containing halide perovskites, i.e., the toxicity of Pb and the low stability under ambient conditions and high-intensity illumination.

Unveiling the truth: Pathogen infections linked to miscarriage: A STROBE-Compliant Mendelian randomization study.

Miscarriage represents a prevalent yet insufficiently studied adverse pregnancy outcome. The definitive causal links between various pathogens and miscarriage remain to be established. To investigate the causal connections between pathogen infections and miscarriage, we utilized a two-sample bidirectional Mendelian randomization (MR) analysis.

Sulfonium perchlorate based near-infrared fluorescent probe targeting lysosome for pH imaging in living cells and tumor-bearing mice.

Due to the accumulation of lactate and other acidic metabolites from insufficient blood supply and hypoxia, the acidic microenvironment of tumors not only accelerates tumor growth and spread but may also affect immune cell function, thereby aiding tumor development. Therefore, real-time monitoring of pH fluctuations in intracellular and living systems provides crucial insights into physiological and pathological processes. This research introduced a novel NIR fluorescent probe, termed SOH, for pH imaging in living cells and tumor-bearing mice.

Unveiling the mystery: Investigating the debate surrounding mitochondrial DNA copy number and Sjögren syndrome using Mendelian randomization analysis.

Numerous studies have investigated the relationship between mitochondrial DNA (mtDNA) copy number and Sjögren syndrome (SS). However, the conclusions remain inconclusive, with conflicting findings. The genome-wide association study summary statistics for mtDNA copy number were obtained from 2 sources: a cohort of 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the UK Biobank, and a dataset of 395,718 UK Biobank participants.

Structure of the microtubule anchoring factor NEDD1 bound to the γ-tubulin ring complex.

The γ-tubulin ring complex (γ-TuRC) is an essential multiprotein assembly, in which γ-tubulin, GCP2-6, actin, MZT1 and MZT2 form an asymmetric cone-shaped structure that provides a template for microtubule nucleation. The γ-TuRC is recruited to microtubule organizing centers (MTOCs), such as centrosomes and pre-existing mitotic spindle microtubules, via the evolutionarily-conserved attachment factor NEDD1. NEDD1 contains an N-terminal WD40 domain that binds to microtubules, and a C-terminal domain that associates with the γ-TuRC.

Decoding skin mysteries: Unveiling the link between microbiota and keloid scars through a Mendelian randomization study.

The cause of keloids remains unclear, but studies suggest a link between skin microbiota and keloid formation. However, the causal relationship has not been confirmed. This study utilized Genome-Wide Association Studies (GWAS) data from 2 population-based German cohorts, comprising a total of 1656 skin samples.

Pd-Catalyzed Dual C-H Activation/Cyclization: Convergent and Divergent Synthesis of 1-Azahelicenes.

Herein, we report a convergent synthesis of 1-azahelicenes using easily available quinoline derivatives and cyclic diaryliodonium salts as starting materials. This reaction undergoes a palladium-catalyzed dual C-H activation/cyclization process to give facile access to a wide range of 1-aza[5]helicenes and 1-aza[6]helicenes with abundant functional groups (including F, Cl, Br, I, CF, SeR, SR, and heteroaryl) in moderate to excellent yields, thereby providing new opportunities to fine-tune the properties of the helicene backbone. In addition, the obtained products could be further transformed into helicene-based Lewis base catalysts and redox switch materials easily.

Partial closure of the γ-tubulin ring complex by CDK5RAP2 activates microtubule nucleation.

Microtubule nucleation is templated by the γ-tubulin ring complex (γ-TuRC), but its structure deviates from the geometry of α-/β-tubulin in the microtubule, explaining the complex's poor nucleating activity. Several proteins may activate the γ-TuRC, but the mechanisms underlying activation are not known. Here, we determined the structure of the porcine γ-TuRC purified using CDK5RAP2's centrosomin motif 1 (CM1).

New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study.

Background: No intervention definitively extends transplant-free survival in primary sclerosing cholangitis (PSC). Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), may enhance PSC prognosis, but their efficacy is debated.

Methods: We analyzed HMGCR single-nucleotide polymorphisms from published genome-wide association studies using Mendelian randomization to assess the causal relationship between HMGCR and PSC risk.