FBXO9 mediated the ubiquitination and degradation of YAP in a GSK-3β-dependent manner.

The Hippo signaling pathway effector YAP (Yes-associated protein) serves as a critical transcriptional regulator involved in a wide range of biological processes, including oncogenesis. Despite its potential as a therapeutic target, pharmacologically targeting the Hippo/YAP axis remains challenging, necessitating further exploration of the mechanisms governing YAP regulation. In this study, we identify the Cullin-RING E3 ligase complex SCF-FBXO9-CRL1 as a novel posttranslational regulator of YAP stability.

Angiotensin-(1-7) Mitigates Progression from Acute Kidney Injury to Chronic Kidney Disease Via Renin-Angiotensin System Modulation in a Murine Model.

 Acute kidney injury (AKI) often progresses to chronic kidney disease (CKD), presenting a significant clinical challenge. The renin-angiotensin system (RAS), particularly the protective arm involving Angiotensin-(1-7) (Ang-(1-7)), offers a potential therapeutic target to mitigate this progression. This study explores the effects of Ang-(1-7) in a murine model of ischemia-reperfusion (I/R) injury-induced AKI.

S-palmitoylation in bone biology: emerging insights and therapeutic potential.

S-Palmitoylation, the reversible covalent attachment of palmitate to cysteine residues, is a dynamic post-translational lipid modification that regulates the localization, stability, and function of a wide array of proteins. Although traditionally linked to membrane trafficking and signaling, recent preliminary studies have begun to reveal its potential role in bone biology, underscoring its significant research value. This review highlights current advances in detection methodologies-particularly the use of H labeling and acyl-biotin exchange (ABE) techniques-that have enabled more precise mapping of the palmitoyl-proteome.

Influence of intravenous iron therapy on mortality and cardiovascular events of patients on hemodialysis: A meta-analysis.

Intravenous (IV) iron is widely utilized to manage anemia in patients undergoing maintenance hemodialysis; however, its long-term safety remains uncertain. This meta-analysis aimed to evaluate the impact of IV iron on all-cause mortality and major adverse cardiovascular events (MACEs) within this population. We conducted a systematic search of PubMed, Embase, Cochrane Library, Web of Science, Wanfang, and CNKI up to March 2025 for randomized controlled trials (RCTs) that compared IV iron with placebo/usual care, oral iron, or varying doses of IV iron in adult hemodialysis patients.

NRXN3-NLGN1 complex influences the development of depression induced by maternal separation in rats.

Early-life stress (ELS) increases the risk of major depressive disorder in children and adolescents. However, the molecular and cellular mechanisms of major depressive disorder (MDD) induced by ELS are poorly understood. Here, we establish a stress model in rats in which maternal separation stress (MS) during the postnatal period increases susceptibility to restraint stress (RS) later in life.

SETDB1 recruits CBX3 to regulate the SIRT4/PTEN axis, inhibiting autophagy and promoting ischemia-reperfusion-induced kidney injury.

Ischemia-reperfusion (I/R) injury is a significant factor in the development of acute kidney injury (AKI), particularly in clinical scenarios, such as kidney transplantation, cardiac surgery, and severe hypotension. Autophagy, a critical process that eliminates damaged cellular components, has been shown to mitigate I/R injury by reducing oxidative stress and enhancing cell survival. However, when autophagy is disrupted, it can exacerbate kidney damage.

Correction: Zeng et al. Hedgehog Signaling: Linking Embryonic Lung Development and Asthmatic Airway Remodeling. 2022, , 1774.

In the original publication [...

Severe asthma beyond bronchodilators: Emerging therapeutic approaches.

Asthma is characterized by reversible airway inflammation, obstruction, and structural remodeling, which lead to the eosinophils and lymphocytes accumulation at inflammation sites and the release of inflammatory cells, like mast cells and dendritic cells, from lungs' epithelial and smooth muscle cells that trigger the activation and release of cytokines and chemokines, attracting more cells and contributing to asthma development. Available pharmacological interventions, like bronchodilators and anti-inflammatory agents, are considered generally safe and effective to treat asthma, but many affected individuals with severe asthma still struggle with symptom control. This review highlights recent innovative therapies, such as chemoattractant receptor-homologous molecule expressed on Th2 cell (CRTH2) antagonists, S-nitrosoglutathione reductase (GSNOR) and phosphodiesterase (PDE) inhibitors, and other novel biological agents, which offer potential new strategies for managing severe asthma and may alter the disease's course.

Relationship of serum calcium concentration with chronic kidney disease and mortality in type 2 diabetes mellitus patients: evidence from the NHANES 1999-2018.

Objectives: This study aims to explore the relationship of serum calcium (Ca) concentration with diabetic kidney disease (DKD) and all-cause mortality among type 2 diabetes mellitus (T2DM) patients using National Health and Nutrition Examination Surveys (NHANES).

Methods: Data of T2DM patients aged ≥ 40 years were screened from the NHANES database from 1999 to 2018. The outcomes were the risk of DKD diagnosed by urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.

The Selective Endothelin Receptor Antagonist SC0062 in IgA Nephropathy: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

Key Points: Patients with IgA nephropathy and significant proteinuria are at high risk of progressive kidney function loss and kidney failure. We report the results of a clinical trial assessing the selective endothelin receptor antagonist SC0062 for the treatment of IgA nephropathy. SC0062 led to clinically meaningful improvements in proteinuria and did not increase risk of peripheral edema at higher doses.

m6A demethylase FTO transcriptionally activated by SP1 improves ischemia reperfusion-triggered acute kidney injury by activating Ambra1/ULK1-mediated autophagy.

Ischemia reperfusion (I/R) was considered as one of main causes of acute kidney injury (AKI). However, the exact mechanism remains unclear. Here, this study aimed to investigate the role and mechanism of the m6A demethylase fat mass and obesity-associated (FTO) protein in I/R-induced AKI.

Smoking-induced CCNA2 expression promotes lung adenocarcinoma tumorigenesis by boosting AT2/AT2-like cell differentiation.

Lung adenocarcinoma (LUAD), a type of non-small cell lung cancer (NSCLC), originates from not only bronchial epithelial cells but also alveolar type 2 (AT2) cells, which could differentiate into AT2-like cells. AT2-like cells function as cancer stem cells (CSCs) of LUAD tumorigenesis to give rise to adenocarcinoma. However, the mechanism underlying AT2 cell differentiation into AT2-like cells in LUAD remains unknown.

Phosphorylation of human glioma-associated oncogene 1 on Ser937 regulates Sonic Hedgehog signaling in medulloblastoma.

Aberrant activation of sonic hedgehog (SHH) signaling and its effector transcriptional factor GLI1 are essential for oncogenesis of SHH-dependent medulloblastoma (MB) and basal cell carcinoma (BCC). Here, we show that SHH inactivates p38α (MAPK14) in a smoothened-dependent manner, conversely, p38α directly phosphorylates GLI1 on Ser937/Ser941 (human/mouse) to induce GLI1's proteasomal degradation and negates the transcription of SHH signaling. As a result, Gli1 loss-of-function knock-in significantly reduces the incidence and severity of smoothened-M2 transgene-induced spontaneous MB, whereas Gli1 gain-of-function knock-in phenocopies Gli1 transgene in causing BCC-like proliferation in skin.

Inhibition of non-muscular myosin light chain kinase accelerates the clearance of inflammatory cells by promoting the lysosome-mediated cell death.

Infections like COVID-19 are the primary cause of death around the world because they can cause acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and sepsis. Inflammatory cells serve as crucial protective barriers in these diseases. However, excessive accumulation of inflammatory cells is also one of the major causes of organ damage.

Pegmolesatide for the treatment of anemia in patients undergoing dialysis: a randomized clinical trial.

Background: Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies.

Methods: A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022.

A novel link between melatonin and circ_0005753/PTBP1/TXNIP regulatory network in the modulation of osteogenic potential in mesenchymal stem cells.

Labeled with pluripotent potential, the transplantation of bone marrow mesenchymal stem cells (BMSCs) is considered as a promising strategy for treating osteoporosis (OP). Melatonin (MEL) has been investigated to be an essential regulator involved in bone metabolism, as well as BMSCs differentiation. Circular RNAs (circRNAs) are a unique kind of non-coding RNA and play an important regulatory role in OP.

Smurf1 polyubiquitinates on K285/K282 of the kinases Mst1/2 to attenuate their tumor-suppressor functions.

Sterile 20-like kinases Mst1 and Mst2 (Mst1/2) and large tumor suppressor 1/2 are core kinases to mediate Hippo signaling in maintaining tissue homeostasis. We have previously demonstrated that Smad ubiquitin (Ub) regulatory factor 1 (Smurf1), a HECT-type E3 ligase, ubiquitinates and in turn destabilizes large tumor suppressor 1/2 to induce the transcriptional output of Hippo signaling. Here, we unexpectedly find that Smurf1 interacts with and polyubiquitinates Mst1/2 by virtue of K27- and K29-linked Ub chains, resulting in the proteasomal degradation of Mst1/2 and attenuation of their tumor-suppressor functions.

Effect of Dexmedetomidine on Postoperative Plasma Neurofilament Light Chain in Elderly Patients Undergoing Thoracoscopic Surgery: A Prospective, Randomized Controlled Trial.

Purpose: Dexmedetomidine exerts a neuroprotective effect, however, the mechanism underlying this effect remains unclear. This study aimed to explore whether dexmedetomidine can reduce the increase in neurofilament light chain (NfL) protein concentration to play a neuroprotective role during thoracoscopic surgery.

Patients And Methods: Patients aged ≥60 years undergoing general anesthesia for thoracoscopic surgery were randomly assigned to receive dexmedetomidine (group D) or not receive dexmedetomidine (group C).

Effect of intravenous vs. inhaled penehyclidine on respiratory mechanics in patients during one-lung ventilation for thoracoscopic surgery: a prospective, double-blind, randomised controlled trial.

Background: Minimising postoperative pulmonary complications (PPCs) after thoracic surgery is of utmost importance. A major factor contributing to PPCs is the driving pressure, which is determined by the ratio of tidal volume to lung compliance. Inhalation and intravenous administration of penehyclidine can improve lung compliance during intraoperative mechanical ventilation.