NEDD4-Mediated GSNOR Degradation Aggravates Cardiac Hypertrophy and Dysfunction.

Background: The decrease in S-nitrosoglutathione reductase (GSNOR) leads to an elevation of S-nitrosylation, thereby exacerbating the progression of cardiomyopathy in response to hemodynamic stress. However, the mechanisms under GSNOR decrease remain unclear. Here, we identify NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) as a novel molecule that plays a crucial role in the pathogenesis of pressure overload-induced cardiac hypertrophy, by modulating GSNOR levels, thereby demonstrating significant therapeutic potential.

Enhancing Lesion Detection in Inflammatory Myelopathies: A Deep Learning-Reconstructed Double Inversion Recovery MRI Approach.

Background And Purpose: The imaging of inflammatory myelopathies has advanced significantly over time, with MRI techniques playing a pivotal role in enhancing lesion detection. However, the impact of deep learning (DL)-based reconstruction on 3D double inversion recovery (DIR) imaging for inflammatory myelopathies remains unassessed. This study aims to compare acquisition time, image quality, diagnostic confidence, and lesion detection rates among sagittal T2WI, standard DIR, and DL -reconstructed DIR in patients with inflammatory myelopathies.

Programmable and flexible wood-based origami electronics.

Natural polymer substrates are gaining attention as substitutes for plastic substrates in electronics, aiming to combine high performance, intricate shape deformation, and environmental sustainability. Herein, natural wood veneer is converted into a transparent wood film (TWF) substrate. The combination of 3D printing and origami technique is established to create programmable wood-based origami electronics, which exhibit superior flexibility with high tensile strength (393 MPa) due to the highly aligned cellulose fibers and the formation of numerous intermolecular hydrogen bonds between them.

Diagnostic Utility of a 90-Gene Expression Assay (Canhelp-Origin) for Patients with Metastatic Cancer with an Unclear or Unknown Diagnosis.

Background: Metastatic cancers with unclear or unknown origins pose significant challenges in diagnosis and management, frequently leading to suboptimal outcomes. Studies have demonstrated that a 90-gene expression assay is effective in predicting the primary origin and guiding the site-specific therapy to improve prognosis. This study aimed to evaluate the clinical effectiveness of a 90-gene expression assay in patients with unclear or unknown diagnoses.

Population Pharmacokinetics of Xeligekimab: An Anti-IL-17A Monoclonal Antibody, in Patients with Moderate to Severe Plaque Psoriasis.

Xeligekimab, a recombinant fully human IgG4 monoclonal antibody, has been strategically developed to target IL-17A and is presently in the developmental phase for treating moderate to severe plaque psoriasis. This study aims to investigate the pharmacokinetic profile of Xeligekimab, utilizing data derived from clinical trials specifically conducted in Chinese patients. The study conducted a population pharmacokinetic (PopPK) analysis involving 614 patients with plaque psoriasis.

USP28 Serves as a Key Suppressor of Mitochondrial Morphofunctional Defects and Cardiac Dysfunction in the Diabetic Heart.

Background: The majority of people with diabetes are susceptible to cardiac dysfunction and heart failure, and conventional drug therapy cannot correct diabetic cardiomyopathy progression. Herein, we assessed the potential role and therapeutic value of USP28 (ubiquitin-specific protease 28) on the metabolic vulnerability of diabetic cardiomyopathy.

Methods: The type 2 diabetes mouse model was established using db/db leptin receptor-deficient mice and high-fat diet/streptozotocin-induced mice.

Effects of spectral smearing on speech understanding and masking release in simulated bilateral cochlear implants.

Differences in spectro-temporal degradation may explain some variability in cochlear implant users' speech outcomes. The present study employs vocoder simulations on listeners with typical hearing to evaluate how differences in degree of channel interaction across ears affects spatial speech recognition. Speech recognition thresholds and spatial release from masking were measured in 16 normal-hearing subjects listening to simulated bilateral cochlear implants.

An MRI-Based Radiomics Nomogram for Differentiation of Benign and Malignant Vertebral Compression Fracture.

Rationale And Objectives: This study aimed to develop and validate a magnetic resonance imaging (MRI)-based radiomics nomogram combining radiomics signatures and clinical factors to differentiate between benign and malignant vertebral compression fractures (VCFs).

Materials And Methods: A total of 189 patients with benign VCFs (n = 112) or malignant VCFs (n = 77) were divided into training (n = 133) and validation (n = 56) cohorts. Radiomics features were extracted from MRI T1-weighted images and short-TI inversion recovery images to develop the radiomics signature, and the Rad score was constructed using least absolute shrinkage and selection operator regression.

Population Pharmacokinetic Analysis of Dorzagliatin in Healthy Subjects and Patients with Type 2 Diabetes Mellitus.

Background And Objectives: Dorzagliatin is a first-in-class small molecule glucokinase activator (GKA) that improves pancreatic insulin secretion behavior and regulates hepatic glucose conversion in a glucose concentration-dependent manner. The primary objective of this study was to develop a population pharmacokinetic model of dorzagliatin to evaluate the influence of covariates, such as demographic characteristics and liver and kidney function, on the pharmacokinetics of dorzagliatin and provide a basis for medication guidance.

Method: The pharmacokinetic data of dorzagliatin in this study came from six clinical trials.

Effect of Natural Aging on Cold Forming Performance of 2219 Aluminum Alloy.

To facilitate the manufacturing of the thin-walled components of 2219 aluminum alloy, the quenching-forming-aging (Q-F-A) process has been increasingly utilized. However, natural aging (NA) after quenching significantly affects the cold forming performance of this alloy. In this study, experiments are conducted to investigate the effect of NA time on the cold forming performance of 2219 aluminum alloy.

α- and β-Genotyping of Thalassemia Patients Based on a Multimodal Liver MRI Radiomics Model: A Preliminary Study in Two Centers.

Background: So far, there is no non-invasive method that can popularize the genetic testing of thalassemia (TM) patients on a large scale. The purpose of the study was to investigate the value of predicting the α- and β- genotypes of TM patients based on a liver MRI radiomics model.

Methods: Radiomics features of liver MRI image data and clinical data of 175 TM patients were extracted using Analysis Kinetics (AK) software.

Population pharmacokinetic and dose optimization of mycophenolic acid in children with anti-neutrophilic cytoplasmic antibody-associated nephritis.

Purpose: Anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis is a rare autoimmune disease. Mycophenolic acid (MPA) is widely used for ANCA-associated nephritis (AAN) but with large pharmacokinetic variability. This study aims to investigate clinical factors impacting MPA disposition in pediatric AAN.

The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice.

Ageing-associated functional decline of organs and increased risk for age-related chronic pathologies is driven in part by the accumulation of senescent cells, which develop the senescence-associated secretory phenotype (SASP). Here we show that procyanidin C1 (PCC1), a polyphenolic component of grape seed extract (GSE), increases the healthspan and lifespan of mice through its action on senescent cells. By screening a library of natural products, we find that GSE, and PCC1 as one of its active components, have specific effects on senescent cells.

Qualitative and Quantitative Wall Enhancement on Magnetic Resonance Imaging Is Associated With Symptoms of Unruptured Intracranial Aneurysms.

Background And Purpose: Aneurysmal wall enhancement (AWE) on vessel wall magnetic resonance imaging (VW-MRI) has been described as a new imaging biomarker of unstable unruptured intracranial aneurysms (UIAs). Previous studies of symptomatic UIAs are limited due to small sample sizes and lack of AWE quantification. Our study aims to investigate whether qualitative and quantitative assessment of AWE can differentiate symptomatic and asymptomatic UIAs.

[Retracted] Epigenetic silencing of miR‑130a ameliorates hemangioma by targeting tissue factor pathway inhibitor 2 through FAK/PI3K/Rac1/mdm2 signaling.

Following the publication of this paper, it was drawn to the authors' attention by an interested reader that some tumours featured in Fig. 6A of the above paper were strikingly similar to those featured in Fig. 8A of an article appearing in the same journal [Fan F‑Y, Deng R, Yi H, Sun H‑P, Zeng Y, He G‑C and Su Y: The inhibitory effect of MEG3/miR‑214/AIFM2 axis on the growth of T‑cell lymphoblastic lymphoma.

Genotype-Guided Dosing of Warfarin in Chinese Adults: A Multicenter Randomized Clinical Trial.

Background: Warfarin is an effective treatment for thromboembolic disease but has a narrow therapeutic index; optimal anticoagulation dosage can differ tremendously among individuals. We aimed to evaluate whether genotype-guided warfarin dosing is superior to routine clinical dosing for the outcomes of interest in Chinese patients.

Methods: We conducted a multicenter, randomized, single-blind, parallel-controlled trial from September 2014 to April 2017 in 15 hospitals in China.

Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke.

Background: In acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy.

Methods: We conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.

Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma.

Background: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials.

Methods: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone.

Simultaneous silencing of TGF-β1 and COX-2 reduces human skin hypertrophic scar through activation of fibroblast apoptosis.

Excessive skin scars due to elective operations or trauma represent a challenging clinical problem. Pathophysiology of hypertrophic scars entails a prolonged inflammatory and proliferative phase of wound healing. Over expression of TGF-β1 and COX-2 play key regulatory roles of the aberrant fibrogenic responses and proinflammatory mediators.

Population pharmacokinetics and Bayesian estimation of tacrolimus exposure in Chinese liver transplant patients.

What Is Known And Objectives: Tacrolimus (TAC) is widely used as part of immunosuppressive regimens. There is great interindividual variation on the disposition of TAC. The aim of this study was to develop a population pharmacokinetic (PPK) model for Chinese liver transplant patients and evaluate genetic polymorphism and other possible factors on the PK parameters.

Clinical Outcome of Double Kissing Crush Versus Provisional Stenting of Coronary Artery Bifurcation Lesions: The 5-Year Follow-Up Results From a Randomized and Multicenter DKCRUSH-II Study (Randomized Study on Double Kissing Crush Technique Versus Provisional Stenting Technique for Coronary Artery Bifurcation Lesions).

Background: Provisional stenting is effective for anatomic simple bifurcation lesions. Double kissing crush stenting reduces the 1-year rate of target lesion revascularization. This study aimed to investigate the 5-year clinical results of the DKCRUSH-II study (Randomized Study on Double Kissing Crush Technique Versus Provisional Stenting Technique for Coronary Artery Bifurcation Lesions).