BCL11A +58/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate.

Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal hemoglobin (HbF) response, we investigated editing both +58 and +55 enhancers. Rhesus macaques transplanted with edited hematopoietic stem/progenitor cells (HSPCs) following busulfan conditioning exhibited durable, high-level (∼90%) editing frequencies post transplantation with sustained HbF reactivation over 4 years, without hematological perturbations.

Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

Background: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1.

Prognostic Nutritional Index as a Prognostic Factor for Very Early-Stage Hepatocellular Carcinoma.

Introduction: Field factors play more important roles in predicting the outcomes of patients compared with tumor factors in early-stage hepatocellular carcinoma (HCC). However, the prognostic ability of noninvasive serum marker scores for hepatic fibrosis and liver functional reserve on very early-stage HCC is still not yet determined. We aimed to investigate the performance of these serum marker scores in predicting the prognoses of patients with very early-stage HCC.

Elranatamab in relapsed or refractory multiple myeloma: the MagnetisMM-1 phase 1 trial.

Multiple myeloma (MM) is a plasma cell malignancy expressing B cell maturation antigen (BCMA). Elranatamab, a bispecific antibody, engages BCMA on MM and CD3 on T cells. The MagnetisMM-1 trial evaluated its safety, pharmacokinetics and efficacy.

Hispidin-enriched Sanghuangporus sanghuang mycelia SS-MN4 ameliorate disuse atrophy while improving muscle endurance.

Background: Disuse atrophy is a frequent cause of muscle atrophy, which can occur in individuals of any age who have been inactive for a prolonged period or immobilization. Additionally, acute diseases such as COVID-19 can cause frequent sequelae and exacerbate muscle wasting, leading to additional fatigue symptoms. It is necessary to investigate potent functional nutrients for muscle reinforcement in both disuse atrophy and fatigue to ensure better physical performance.

Ocular Surface Evaluation in Immunoglobulin G4-Related Ophthalmic Disease.

Purpose: To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients.

Design: Cross-sectional, matched case-control comparison study.

Methods: This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.

Mesocosm experimental study on sustainable riparian restoration using sediment-modified planting eco-concrete.

The continued deterioration of riparian ecosystems is a worldwide concern, which can lead to soil erosion, plant degradation, biodiversity loss, and water quality decline. Here, taking into account waste resource utilization and eco-environmental friendliness, the sediment-modified planting eco-concrete with both H. verticillata and T.

Global climatological data of ocean thermohaline parameters derived from WOA18.

This is a global ocean climatological dataset of 17 thermohaline parameters such as isothermal layer (ITL) depth (h), mixed layer (ML) depth (h), thermocline gradient (G), pycnocline gradient (G) determined from temperature (T) and salinity (S) profiles of the National Centers for Environmental Information (NCEI) world ocean atlas 2018 (WOA18) using the double gradient method along with the identity-index (i-index) showing the quality of the determination. With the identified (h, h) and (G, G), other parameters such as ITL heat content (H), mixed layer fresh-water content (F), maximum thermocline gradient (G), thermocline depth (h), temperature at thermocline depth (T), maximum density gradient G), pycnocline depth (h), density at pycnocline depth (ρ), and (h - h) (barrier layer if positive or compensated layer if negative). The dataset is located at the NOAA/NCEI website ( https://doi.

Differential Associations of GAD Antibodies (GADA) and C-Peptide With Insulin Initiation, Glycemic Responses, and Severe Hypoglycemia in Patients Diagnosed With Type 2 Diabetes.

Objective: We examined the associations of GAD antibodies (GADA) and C-peptide (CP) with insulin initiation, glycemic responses, and severe hypoglycemia in type 2 diabetes (T2D).

Research Design And Methods: In 5,230 Chinese patients (47.6% men) with T2D (mean ± SD age: 56.

Antrodin C Isolated from Antrodia Cinnamomea Induced Apoptosis through ROS/AKT/ERK/P38 Signaling Pathway and Epigenetic Histone Acetylation of TNFα in Colorectal Cancer Cells.

Background: Antrodin C, a maleimide derivative compound isolated from the ethanol extract of the mycelium of , is an endemic fungus of Taiwan and a potential chemoprotective agent. However, the molecular mechanisms underlying the mode of action of antrodin C on cancer cells, especially in human colorectal cancer (CRC), remain unclear.

Methods: The cell death and ROS of the antrodin-C-treated HCT-116 cells were measured by annexin V-FITC/propidium iodide staining, DCFDA, and Fluo-3 fluorescence staining assays.

Acute Infarcts on Brain MRI Following Aortic Arch Repair With Circulatory Arrest: Insights From the ACE CardioLink-3 Randomized Trial.

Background: to investigate the frequency and distribution of new ischemic brain lesions detected by diffusion-weighted imaging on brain magnetic resonance imaging after aortic arch surgery.

Methods: This preplanned secondary analysis of the randomized, controlled ACE (Aortic Surgery Cerebral Protection Evaluation) CardioLink-3 trial compared the safety and efficacy of innominate versus axillary artery cannulation during elective proximal aortic arch surgery. Participants underwent pre and postoperative magnetic resonance imaging.

A Randomized Controlled Trial of Psychological Intervention to Improve Satisfaction for Patients with Depression Undergoing TKA: A 2-Year Follow-up.

Background: The overall satisfaction of patients after total knee arthroplasty (TKA) is approximately 80%, and current studies have demonstrated that patients with depression may have lower patient satisfaction. The purpose of this study was to determine whether perioperative psychological intervention in patients with depression improves the clinical outcomes and patient satisfaction in patients undergoing TKA.

Methods: Six hundred patients who underwent primary TKA from May 2016 to January 2018 were prospectively screened for eligibility.

Randomized, Controlled Trial Comparing Mitral Valve Repair With Leaflet Resection Versus Leaflet Preservation on Functional Mitral Stenosis: The CAMRA CardioLink-2 Study.

Background: Equipoise exists between the use of leaflet resection and preservation for surgical repair of mitral regurgitation caused by prolapse. We therefore performed a randomized, controlled trial comparing these 2 techniques, particularly in regard to functional mitral stenosis.

Methods: One hundred four patients with degenerative mitral regurgitation surgically amenable to either leaflet resection or preservation were randomized at 7 specialized cardiac surgical centers.

Severe dysfunctional tear syndrome patients and resolution of central corneal staining: retrospective cohort study.

Purpose: Severe dry eye is widely prevalent yet difficult to treat. This study aims to evaluate for improvement in epithelial status and the risk factors for lack of improvement in a cohort of patients in Singapore with severe dry eye.

Methods: We retrospectively identified 1712 patients with severe dry eye (≥grade 3 Delphi) in at least one eye, referred to a tertiary centre dry eye clinic from 2006 to 2017.

Coupling Between Interleukin-1R1 and Necrosome Complex Involves in Hemin-Induced Neuronal Necroptosis After Intracranial Hemorrhage.

Background and Purpose- Accumulated evidence suggests that hemin-a breakdown product of hemoglobin-plays a pivotal role in the inflammatory injuries that result after hemorrhagic stroke through the Toll Like Receptor 2-Toll Like Receptor 4 signal pathway. However, the mechanism of how hemin triggers neuronal necroptosis directly after intracranial hemorrhage (ICH) is still an area of active research. As animal model and preclinical studies have shown, the recombinant interleukin-1 receptor antagonist (IL-1RA) improves clinical outcomes after stroke.

Endovascular MR-guided Renal Embolization by Using a Magnetically Assisted Remote-controlled Catheter System.

Purpose To assess the feasibility of a magnetically assisted remote-controlled (MARC) catheter system under magnetic resonance (MR) imaging guidance for performing a simple endovascular procedure (ie, renal artery embolization) in vivo and to compare with x-ray guidance to determine the value of MR imaging guidance and the specific areas where the MARC system can be improved. Materials and Methods In concordance with the Institutional Animal Care and Use Committee protocol, in vivo renal artery navigation and embolization were tested in three farm pigs (mean weight 43 kg ± 2 [standard deviation]) under real-time MR imaging at 1.5 T.

The Chinese Version of the Gotland Male Depression Scale (GMDS): Mokken scaling.

Objective: Invariant item ordering (IIO) is defined as the extent to which items have the same order for each respondent who completes a scale. IIO is crucial for establishing a scale hierarchy that is replicable across samples; however, no research has demonstrated IIO in the Gotland Male Depression Scale (GMDS). The aim of this study was to determine if an IIO hierarchy of depressive symptoms existed in a clinical sample of men who completed the GMDS.

Pharmacokinetics and safety of ezetimibe/simvastatin combination tablet: an open-label, single-dose study in healthy Chinese subjects.

Background And Objectives: Ezetimibe/simvastatin combination tablet has been approved for the treatment of high low-density lipoprotein cholesterol (LDL-C) levels in patients with primary hypercholesterolaemia or mixed hypercholesterolaemia as adjunctive therapy to diet, when diet alone is insufficient in lowering cholesterol. The aims of this study were to assess the pharmacokinetics and safety of an ezetimibe/simvastatin combination tablet after oral single-dose administration in healthy Chinese subjects including sex-related differences in pharmacokinetics.

Methods: This was an open-label, single-dose study.

Improved method for production of antibodies against T-2 toxin and diacetoxyscirpenol in rabbits.

A new, improved approach for the production of antibodies against T-2 toxin and diacetoxyscirpenol (DAS) was developed. The method involves the use of immunogens which were prepared by conjugating O-carboxymethoxyl oxime (CMO) derivatives of both toxins to bovine serum albumin (BSA). Isomers a and b of CMO-T-2 toxin and isomer b of CMO-DAS were tested.

Detection of T-2 toxin by an improved radioimmunoassay.

T-2 toxin in serum, urine, and saline was analyzed by a modified radioimmunoassay procedure. The specimens were added directly to the assay tubes without extraction steps. The reaction between antibody and ligands was optimal at 1 h.