Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis.

SOX9 is a crucial transcriptional regulator of cartilage development and homeostasis. Dysregulation of is associated with a wide spectrum of skeletal disorders, including campomelic dysplasia, acampomelic campomelic dysplasia, and scoliosis. Yet how variants contribute to the spectrum of axial skeletal disorders is not well understood.

Application of Gene Editing in Triple-Negative Breast Cancer Research.

With the rapid development of gene editing technology, its application in breast cancer has gradually become the focus of research. This article reviews the application of gene editing technology in the treatment of breast cancer, and discusses its challenges and future development directions. The key application areas of gene editing technology in the treatment of breast cancer will be outlined, including the discovery of new therapeutic targets and the development of drugs related to the pathway.

First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial.

Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression. Here we investigated the efficacy and safety of cadonilimab (PD-1/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody) plus chemotherapy as first-line treatment in G/GEJ adenocarcinoma. The prespecified interim analysis is reported here.

Oleandrin inhibits osteoclast differentiation by targeting the LRP4/MAPK/NF-κB signalling pathway to treat osteoporosis.

Osteoporosis is a common inflammation-related disease in which the release of proinflammatory cytokines promotes bone loss. Oleandrin is a monomer compound extracted from the leaves of the Nerium oleander plant, has been shown to exert an anti-inflammatory effect on a variety of inflammation-related diseases. However, its role in osteoporosis and the underlying mechanisms remain unclear.

Balancing the solar irradiance needs: optimising growth in sphagnum palustre through tailored UV-B effects.

Background: The carbon sequestration potential and water retention capacity of peatlands are closely linked to the growth dynamics of Sphagnum mosses. However, few studies have focused on the response of Sphagnum moss growth dynamics to UV-B radiation, and existing research has emphasized species differences. In this study, Sphagnum palustre L.

The role of B cells in the pathogenesis of type 1 diabetes.

Type 1 diabetes (T1D) is a metabolic disorder caused by a complete lack of insulin, primarily manifested by hyperglycemia. The mechanisms underlying the onset of T1D are complex, involving genetics, environment, and various unknown factors, leading to the infiltration of various immune components into the islets. Besides T cells, B cells are now considered important contributors to the pathogenesis of T1D, according to recent studies.

Glecirasib in KRAS-mutated nonsmall-cell lung cancer: a phase 2b trial.

Glecirasib (JAB-21822) is a new covalent oral KRAS-G12C inhibitor. This multicenter, single-arm phase 2b study assessed the efficacy and safety of glecirasib administered orally at 800 mg daily in patients with locally advanced or metastatic KRAS-mutated nonsmall-cell lung cancer. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC).

MTFAP: a comprehensive platform for predicting and analyzing master transcription factors.

Master transcription factors (MTFs) activate gene expression in pluripotent embryonic stem cells (ESCs) by binding to enhancers and super-enhancers, which precisely control ESC fate. Compelling evidence reveals a strong correlation between the operation of MTFs and the initiation and progression of cancer. Nevertheless, the challenge of identifying MTFs imposes a barrier for researchers.

MSC-derived exosomal circMYO9B accelerates diabetic wound healing by promoting angiogenesis through the hnRNPU/CBL/KDM1A/VEGFA axis.

Diabetic foot ulcer (DFU) is a common but devastating complication of diabetes mellitus and might ultimately lead to amputation. Elucidating the regulatory mechanism of wound healing in DFU is quite important for developing DFU management strategies. Here, we show, mecenchymal stem cell (MSC)-derived exosomes promoted the proliferation, migration and angiogenesis of high glucose-treated endothelial cells and reduced cell apoptosis.

A negatively charged region within carboxy-terminal domain maintains proper CTCF DNA binding.

As an essential regulator of higher-order chromatin structures, CCCTC-binding factor (CTCF) is a highly conserved protein with a central DNA-binding domain of 11 tandem zinc fingers (ZFs), which are flanked by amino (N-) and carboxy (C-) terminal domains of intrinsically disordered regions. Here we report that CRISPR deletion of the entire C-terminal domain of alternating charge blocks decreases CTCF DNA binding but deletion of the C-terminal fragment of 116 amino acids results in increased CTCF DNA binding and aberrant gene regulation. Through a series of genetic targeting experiments, in conjunction with electrophoretic mobility shift assay (EMSA), circularized chromosome conformation capture (4C), qPCR, chromatin immunoprecipitation with sequencing (ChIP-seq), and assay for transposase-accessible chromatin with sequencing (ATAC-seq), we uncovered a negatively charged region (NCR) responsible for weakening CTCF DNA binding and chromatin accessibility.

Pathway plaques and diffusion-weighted lesion analysis after endovascular treatment of unruptured intracranial aneurysms: a prospective study.

Objectives: To evaluate the prevalence and predictors of ischemic lesions on thin-slice DWI (2 mm) in endovascular treatments for unruptured intracranial aneurysms (UIA), particularly explore the potential relationship with pathway plaques.

Methods: Participants eligible for endovascular treatments with UIA at a national stroke center between March 2023 and August 2023 were prospectively enrolled. All participants performed thin-slice DWI (slice thickness of 2 mm) before and after procedures.

Adipose-derived stem cell exosomes attenuates myofibroblast transformation via inhibiting autophagy through TGF-β/Smad2 axis in oral submucosal fibrosis.

Oral submucous fibrosis (OSF) is a precancerous condition that poses substantial health risks. OSF is mainly caused by betel nut chewing behavior, but its pathogenesis is still unclear and there is no effective treatment strategy. The transformation of fibroblasts to myofibroblast is the key pathological change in the development of OSF.

Cryptic divergence in and evolutionary dynamics of endangered hybrid Picea brachytyla sensu stricto in the Qinghai-Tibet Plateau.

Background: The visual similarities observed across various plant groups often conceal underlying genetic distinctions. This occurrence, known as cryptic diversity, underscores the key importance of identifying and understanding cryptic intraspecific evolutionary lineages in evolutionary ecology and conservation biology.

Results: In this study, we conducted transcriptome analysis of 81 individuals from 18 natural populations of a northern lineage of Picea brachytyla sensu stricto that is endemic to the Qinghai-Tibet Plateau.

Efficacy, safety, and biomarker analysis of first-line immune checkpoint inhibitors with chemotherapy versus chemotherapy for advanced gastric cancer: a multicenter, retrospective cohort study.

Background: Recent phase III randomized controlled trials have demonstrated that first-line immune checkpoint inhibitors (ICIs) improve prognosis in advanced HER-2-negative gastric cancer patients with programmed death ligand 1 (PD-L1) combined positive score (CPS) higher than 5. However, these findings are not confirmed in real-world settings, and the benefits in PD-L1 CPS < 5 patients remain controversial.

Methods: In this multicenter, retrospective cohort study, data from across thirteen medical centers were analyzed by inverse probability of treatment weighting for matching, alongside univariate and multivariate COX proportional hazard regression models.

Novel insights into cuproptosis inducers and inhibitors.

Cuproptosis is a new pattern of Cu-dependent cell death distinct from classic cell death pathways and characterized by aberrant lipoylated protein aggregation in TCA cycle, Fe-S cluster protein loss, HSP70 elevation, proteotoxic and oxidative stress aggravation. Previous studies on Cu homeostasis and Cu-induced cell death provide a great basis for the discovery of cuproptosis. It has gradually gathered enormous research interests and large progress has been achieved in revealing the metabolic pathways and key targets of cuproptosis, due to its role in mediating some genetic, neurodegenerative, cardiovascular and tumoral diseases.

The Mitochondrial Fusion Promoter M1 Mitigates Cigarette Smoke-Induced Airway Inflammation and Oxidative Stress via the PI3K-AKT Signaling Pathway.

Purpose: This study investigated the efficacy and underlying mechanism of the mitochondrial fusion promoter M1 in mitigating cigarette smoking (CS)-induced airway inflammation and oxidative stress both in vitro and in vivo models.

Methods: Cigarette smoke extract (CSE)-treated airway epithelial cells (BEAS-2B) and CS-exposed mice were pretreated with M1, followed by the measurement of proinflammatory cytokines, oxidative stress, mitochondrial fusion proteins (MFN2 and OPA1) and fission proteins (DRP1 and MFF). Molecular pathways were elucidated through transcriptomic analysis and Western blotting.

CircSpna2 attenuates cuproptosis by mediating ubiquitin ligase Keap1 to regulate the Nrf2-Atp7b signalling axis in depression after traumatic brain injury in a mouse model.

Background: Depression is a common but often overlooked consequence in individuals with post-traumatic brain injury (TBI). Circular RNAs (circRNAs) play essential roles in the nervous system, yet their involvement in the cell death mechanism known as cuproptosis and in TBI-related depression remains unclear.

Objectives: This study aimed to investigate the role of circRNA, specifically circSpna2, in the regulation of cuproptosis and its association with depression in TBI patients.

The Impact of Selenium Deficiency and T-2 Toxin on Zip6 Expression in Kashin-Beck Disease.

This study investigated the expression of Zip6, a gene predominantly located in the placenta, breast, and prostate tissues, in patients with Kashin-Beck disease (KBD). Environmental risk factor models for KBD were developed using low selenium (Se) feeding (with a Se content of 0.02 mg Se/kg in the feed) and exposure to T-2 toxin (200 ng/g*BW/D).

Blood-Brain Barrier Conquest in Glioblastoma Nanomedicine: Strategies, Clinical Advances, and Emerging Challenges.

Glioblastoma (GBM) is a prevalent type of malignancy within the central nervous system (CNS) that is associated with a poor prognosis. The standard treatment for GBM includes the surgical resection of the tumor, followed by radiotherapy and chemotherapy; yet, despite these interventions, overall treatment outcomes remain suboptimal. The blood-brain barrier (BBB), which plays a crucial role in maintaining the stability of brain tissue under normal physiological conditions of the CNS, also poses a significant obstacle to the effective delivery of therapeutic agents to GBMs.

The efficacy and safety of a novel PD-1/CTLA-4 bispecific antibody cadonilimab (AK104) in advanced non-small cell lung cancer: A multicenter retrospective observational study.

Background: For patients with advanced non-small cell lung cancer (NSCLC) who have received frontline immunochemotherapy, subsequent treatment options are limited. As the first dual programmed cell death-1 (PD-1)/cytotoxic T lymphocyte-associated antigen-4 bispecific antibody approved globally, cadonilimab demonstrated potential antitumor activity in advanced NSCLC patients resistant to anti-PD-1/PD-L1 antibodies.

Methods: We retrospectively collected efficacy and safety data from advanced NSCLC patients treated with cadonilimab-based regimens in later therapy lines.