An antibiotic that mediates immune destruction of senescent cancer cells.

Drugs that eliminate senescent cells, senolytics, can be powerful when combined with prosenescence cancer therapies. Using a CRISPR/Cas9-based genetic screen, we identify here SLC25A23 as a vulnerability of senescent cancer cells. Suppressing SLC25A23 disrupts cellular calcium homeostasis, impairs oxidative phosphorylation, and interferes with redox signaling, leading to death of senescent cells.

Analysis of the Genetic Diversity and Genetic Structure of Jiangshan Black Pigs Using Single Nucleotide Polymorphism (SNP) Chips.

The Jiangshan black pig is an indigenous pig breed in China, renowned for its superior meat quality and adaptability to roughage. However, the population of Jiangshan black pigs has dwindled due to the introduction of cosmopolitan pig breeds and the outbreak of African swine fever, putting them at risk of extinction. To offer insights into the conservation and breeding of Jiangshan black pigs, this study involved 118 Jiangshan black pigs as the research subjects and employed the Zhongxin-1 Porcine Breeding Array PLUS chip to detect whole-genome SNPs.

Baseline Performance of Ultrasound-Based Strategies in Breast Cancer Screening Among Chinese Women.

Rationale And Objective: There is a notable absence of robust evidence on the efficacy of ultrasound-based breast cancer screening strategies, particularly in populations with a high prevalence of dense breasts. Our study addresses this gap by evaluating the effectiveness of such strategies in Chinese women, thereby enriching the evidence base for identifying the most efficacious screening approaches for women with dense breast tissue.

Methods: Conducted from October 2018 to August 2022 in Central China, this prospective cohort study enrolled 8996 women aged 35-64 years, divided into two age groups (35-44 and 45-64 years).

Impact of Diabetes on Persistent Radiological Abnormalities and Pulmonary Diffusion Dysfunction in COVID-19 Survivors: A 3-Year Prospective Cohort Study.

Rationale And Objectives: Little is known about the long-term impact of diabetes on lung impairment in COVID-19 survivors over a three-year period. This study evaluated the long-term impact of diabetes on persistent radiological pulmonary abnormalities and lung function impairment in COVID-19 survivors over three years.

Materials And Methods: In this prospective, multicenter, cohort study, pulmonary sequelae were compared between COVID-19 survivors with and without diabetes.

Gonadotropin Activity during Early Folliculogenesis and Implications for Polycystic Ovarian Syndrome and Premature Ovarian Insufficiency: A Narrative Review.

Female fertility depends on the ovarian reserve of follicles, which is determined at birth. Primordial follicle development and oocyte maturation are regulated by multiple factors and pathways and classified into gonadotropin-independent and gonadotropin-dependent phases, according to the response to gonadotropins. Folliculogenesis has always been considered to be gonadotropin-dependent only from the antral stage, but evidence from the literature highlights the role of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) during early folliculogenesis with a potential role in the progression of the pool of primordial follicles.

Sensing and guiding cell-state transitions by using genetically encoded endoribonuclease-mediated microRNA sensors.

Precisely sensing and guiding cell-state transitions via the conditional genetic activation of appropriate differentiation factors is challenging. Here we show that desired cell-state transitions can be guided via genetically encoded sensors, whereby endogenous cell-state-specific miRNAs regulate the translation of a constitutively transcribed endoribonuclease, which, in turn, controls the translation of a gene of interest. We used this approach to monitor several cell-state transitions, to enrich specific cell types and to automatically guide the multistep differentiation of human induced pluripotent stem cells towards a haematopoietic lineage via endothelial cells as an intermediate state.

Integrative Analysis of Histone Acetylation Regulated CYP4F12 in Esophageal Cancer Development.

Current therapeutic strategies for esophageal cancer (EC) patients have yielded limited improvements in survival rates. Recent research has highlighted the influence of drug metabolism enzymes on both drug response and EC development. Our study aims to identify specific drug metabolism enzymes regulated by histone acetylation and to elucidate its molecular and clinical features.

ABBV-319: a CD19-targeting glucocorticoid receptor modulator antibody-drug conjugate therapy for B-cell malignancies.

Glucocorticoids are key components of the standard-of-care treatment regimens for B-cell malignancy. However, systemic glucocorticoid treatment is associated with several adverse events. ABBV-319 is a CD19-targeting antibody-drug conjugate engineered to reduce glucocorticoid-associated toxicities while possessing 3 distinct mechanisms of action (MOA) to increase therapeutic efficacy: (1) antibody-mediated delivery of a glucocorticoid receptor modulator (GRM) payload to activate apoptosis, (2) inhibition of CD19 signaling, and (3) enhanced fragment crystallizable (Fc)-mediated effector function via afucosylation of the antibody backbone.

Effectiveness and safety of ivabradine in Chinese patients with chronic heart failure: an observational study.

Aims: A therapeutic strategy for chronic heart failure (HF) is to lower resting heart rate (HR). Ivabradine is a well-known HR-lowering agent, but limited prospective data exist regarding its use in Chinese patients. This study aimed to evaluate the effectiveness and safety of ivabradine in Chinese patients with chronic HF.

Classification of Myelin Oligodendrocyte Glycoprotein Antibody-Related Disease and Its Mimicking Acute Demyelinating Syndromes in Children Using MRI-Based Radiomics: From Lesion to Subject.

Rationale And Objectives: To develop MRI-based radiomics models from the lesion level to the subject level and assess their value for differentiating myelin oligodendrocyte glycoprotein antibody-related disease (MOGAD) from non-MOGAD acute demyelinating syndromes in pediatrics.

Materials And Methods: 66 MOGAD and 66 non-MOGAD children were assigned to the training set (36/35), internal test set (14/16), and external test set (16/15), respectively. At the lesion level, five single-sequence models were developed alongside a fusion model (combining these five sequences).

Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration.

The development of liver-based adeno-associated virus (AAV) gene therapies is facing concerns about limited efficiency and durability of transgene expression. We evaluated nonhuman primates following intravenous dosing of AAV8 and AAVrh10 vectors for over 2 years to better define the mechanism(s) of transduction that affect performance. High transduction of non-immunogenic transgenes was achieved, although expression declined over the first 90 days to reach a lower but stable steady state.

Unleashing the Power of NR4A1 Degradation as a Novel Strategy for Cancer Immunotherapy.

An effective cancer therapy requires both killing cancer cells and targeting tumor-promoting pathways or cell populations within the tumor microenvironment (TME). We purposely search for molecules that are critical for multiple tumor-promoting cell types and identified nuclear receptor subfamily 4 group A member 1 (NR4A1) as one such molecule. NR4A1 has been shown to promote the aggressiveness of cancer cells and maintain the immune suppressive TME.

3D printing of ultra-high viscosity resin by a linear scan-based vat photopolymerization system.

The current printing mechanism of the bottom-up vat photopolymerization 3D printing technique places a high demand on the fluidity of the UV-curable resin. Viscous high-performance acrylate oligomers are compounded with reactive diluents accordingly to prepare 3D printable UV-curable resins (up to 5000 cps of viscosity), yet original mechanical properties of the oligomers are sacrificed. In this work, an elaborated designed linear scan-based vat photopolymerization system is developed, allowing the adoption of printable UV-curable resins with high viscosity (> 600,000 cps).

TGF-β1/SMAD3 Regulates Programmed Cell Death 5 That Suppresses Cardiac Fibrosis Post-Myocardial Infarction by Inhibiting HDAC3.

Background: Progressive cardiac fibrosis leads to ventricular wall stiffness, cardiac dysfunction, and eventually heart failure, but the underlying mechanism remains unexplored. PDCD5 (programmed cell death 5) ubiquitously expresses in tissues, including the heart; however, the role of PDCD5 in cardiac fibrosis is largely unknown. Therefore, this study aims at exploring the possible role and underlying mechanisms of PDCD5 in the pathogenesis of cardiac fibrosis.

Association of 4qA-Specific Distal D4Z4 Hypomethylation With Disease Severity and Progression in Facioscapulohumeral Muscular Dystrophy.

Background And Objectives: The objective of this study was to examine whether the regional methylation levels at the most distal D4Z4 repeat units (RU) in the 4qA-permissive haplotype were associated with disease severity and progression in facioscapulohumeral muscular dystrophy type 1 (FSHD1).

Methods: This 21-year, retrospective, observational cohort study was conducted at the Fujian Neuromedical Center (FNMC) in China. Methylation levels of the most distal D4Z4 RU, including 10 CpGs, were assessed in all participants by bisulfite sequencing.

Rhodium nanoparticles supported on silanol-rich zeolites beyond the homogeneous Wilkinson's catalyst for hydroformylation of olefins.

Hydroformylation is one of the largest industrially homogeneous processes that strongly relies on catalysts with phosphine ligands such as the Wilkinson's catalyst (triphenylphosphine coordinated Rh). Heterogeneous catalysts for olefin hydroformylation are highly desired but suffer from poor activity compared with homogeneous catalysts. Herein, we demonstrate that rhodium nanoparticles supported on siliceous MFI zeolite with abundant silanol nests are very active for hydroformylation, giving a turnover frequency as high as ~50,000 h that even outperforms the classical Wilkinson's catalyst.

Brain Activation Evoked by Motor Imagery in Pediatric Patients with Complete Spinal Cord Injury.

Background And Purpose: Currently, there is no effective treatment for pediatric patients with complete spinal cord injury. Motor imagery has been proposed as an alternative to physical training for patients who are unable to move voluntarily. Our aim was to reveal the potential mechanism of motor imagery in the rehabilitation of pediatric complete spinal cord injury.