Safety, efficacy, and immunogenicity of a novel IgG degrading enzyme (KJ103): results from two randomised, blinded, phase 1 clinical trials.

The approved intravenous adeno-associated virus (AAV) therapies are limited by the widespread prevalence of pre-existing anti-AAV antibodies in the general population, which are known to restrict patients' ability to receive gene therapy and limit transfection efficacy in vivo. To address this challenge, we have developed a novel recombinant human immunoglobulin G degrading enzyme KJ103, characterized by low immunogenicity and clinical value for the elimination of anti-AAV antibodies in gene transfer. Herein, we conducted two randomized, blinded, placebo-controlled, single ascending dose Phase I studies in China and New Zealand, to evaluate the pharmacokinetics, pharmacodynamics, safety and immunogenicity of KJ103 in healthy volunteers.

The microneme protein1 (MIC1) of Chinese 1 Toxoplasma regulates pyroptosis through the TLR4/NLRP3 pathway in macrophages.

Background: TgMIC1, a soluble adhesion protein that typically facilitates parasite invasion, exhibited varying expression levels among distinct virulence strains of Chinese 1 Toxoplasma. This study aims to explore its role in immunological regulation and its association with diverse postinfection outcomes in Toxoplasma infection.

Methods: First, the mic1 knockout strain Wh3Δmic1 was generated and assessed for its virulence and proliferative capacity.

A nomogram incorporating linezolid and metabolite concentrations for predicting linezolid induced thrombocytopenia in patients with renal impairment.

A nomogram to estimate the risk of linezolid-induced thrombocytopenia in patients with renal impairment is not available. The aim of the study is to develop a nomogram for predicting linezolid-induced thrombocytopenia in patients with renal impairment and to investigate the incremental value of PNU-142300 concentration beyond clinical factors and linezolid trough concentration (C) for risk prediction. Logistic regression was used to identify independent risk factors for linezolid-induced thrombocytopenia in patients with renal impairment and nomograms were established.

Procyanidin B2-3'--Gallate Derived from Grape Seed Polymeric Procyanidins via the Galloyl-Attached Nucleophilic Degradation as a Potential Hepatoprotective Agent.

An effective method was developed for preparing galloylated procyanidins (GPCs) using galloyl-attached nucleophilic degradation. Under degradation conditions optimized through Box-Behnken design and single-factor experiments, two dimeric and three tetrameric GPCs were produced, with the yield of procyanidin B2-3'--gallate (B2-3'-G) reaching up to 232 mg/g (PPCs). The structure of B2-3'-G was identified by UV, FTIR, NMR, CD, MS, and phloroglucinolysis.

A retrospective analysis of transudative pleural effusion due to fibrosing mediastinitis.

Background: Pleural effusion caused by fibrosing mediastinitis is rarely reported. This study aimed to summarize the clinical manifestations, diagnosis and treatment of transudative pleural effusion due to fibrosing mediastinitis.

Methods: Medical records and follow-up data of 7 patients with transudative pleural effusion due to fibrosing mediastinitis in Beijing Chaoyang Hospital between May 2014 and Feb 2018 were retrospectively analyzed.

Population pharmacokinetics and dose optimization of magnesium sulfate in Chinese preeclampsia population.

Objective: To establish the population pharmacokinetics (PPK) of magnesium sulfate (MgSO)in women with preeclampsia (PE), and to determine the key covariates having an effect in magnesium pharmacokinetics in Chinese PE.

Methods: Pregnant women with PE prescribed MgSO4 were enrolled in this prospective study from April 2021 to April 2023. On the initial day of administration, the patients were administered a loading dose of 5 g in conjunction with 10 g of magnesium sulfate as a maintenance dose.

Intratumoral metabolic heterogeneity by F-FDG PET/CT to predict prognosis for patients with thymic epithelial tumors.

Background: The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative F-FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs).

Methods: This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment F-FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured.

Novel l-Cysteine Incomplete Degradation Method for Preparation of Procyanidin B2-3'--Gallate and Exploration of its Anti-inflammatory Activity and Tissue Distribution.

In this study, an effective method for preparation of bioactive galloylated procyanidin B2-3'--gallate (B2-3'-G) was first developed by incomplete depolymerization of grape seed polymeric procyanidins (PPCs) using l-cysteine (Cys) in the presence of citric acid. The structure-activity relationship of B2-3'-G was further evaluated through establishing lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells.

Relationship between bilirubin and systemic lupus erythematosus: A systematic review and meta-analysis.

Aims: Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence worldwide. This study aimed to examine the correlation between serum bilirubin levels and SLE.

Methods: The Cochrane library, Embase, PubMed, and China National Knowledge Infrastructure (CNKI) databases were examined and assessed until March 2023.

Promoting OH Adsorption and Diffusion Enables Ultrahigh Capacity and Rate Capability of Nickel Sulfide Cathode for Aqueous Alkaline Zn-Based Batteries.

Aqueous alkaline Zn-based batteries (AAZBs) possess great promise for large-scale applications thanks to their higher discharging plateau and unique reaction mechanism. However, the capacity and rate capability of Ni-based cathodes are still unsatisfactory due to their insufficient OH adsorption and diffusion ability. Herein, heterostructured Ni S /Ni(OH) nanosheets with outstanding electrochemical performance are synthesized via a facile chemical etching strategy.

Stress aggravates imiquimod-induced psoriasiform inflammation by promoting M1 macrophage polarization.

Psychological stress has long been considered to cause the aggravation and recurrence of psoriasis, but the underlying mechanism remains largely unknown. Here, we used a mouse model of restraint-induced stress and imiquimod (IMQ)-induced psoriasiform inflammation to investigate the crosstalk between stress and the skin immune system and their functions in the pathogenesis of psoriasis. We found that stress aggravated skin inflammation and elevated serum corticosterone (CORT) levels in mice.

Risk factors associated with attendance at postpartum blood pressure follow-up visit in discharged patients with hypertensive disorders of pregnancy.

Background: This study aims to investigate the risk factors for not returning to postpartum blood pressure (BP) follow-up visit at different time points in postpartum discharged hypertensive disorders of pregnancy (HDP) patients. Likewise, females with HDP in China should have a BP evaluation continuously for at least 42 days postpartum and have BP, urine routine, and lipid and glucose screening for 3 months postpartum.

Methods: This study is a prospective cohort study of postpartum discharged HDP patients.

Meta-analysis of cancer risk among end stage renal disease undergoing maintenance dialysis.

Currently, there is no consensus on whether maintenance dialysis increases cancer risk in patients with end-stage renal disease (ESRD). Therefore, this study was to systematically evaluate the risk of cancer among ESRD patients undergoing maintenance dialysis. Related studies on the impact of maintenance dialysis on cancer risk were retrieved from PubMed, Embase, Cochrane Library, and other databases from their respective inceptions to 19 February 2021.

CircRNA Circ_0000118 Regulates Malignancy of Cervical Cancer Cells by Regulating miR-211-5p/miR-377-3p/AKT2 Axis.

CircRNAs are implicated in the development of several cancers. Nevertheless, the involvement of circ_0000118 in the development of cervical cancer (CC) remains unclear. Circ_0000118 levels in tumor tissues and cells were examined by qRT-PCR.

Valence Engineering Enhancing NH Storage Capacity of Manganese Oxides.

Ammonium ions (NH ), as non-metallic charge carriers, are attracting attention in aqueous batteries due to its low molar mass, element sufficiency, and non-toxicity. However, the host materials for NH storage are still limited. Herein, an oxygen defects-rich manganese oxide (MnO ) for NH storage are reported.

Compacting Electric Double Layer Enables Carbon Electrode with Ultrahigh Zn Ion Storage Capability.

Carbon-based cathodes for aqueous zinc ion hybrid supercapacitors (ZHSCs) typically undergo low Zn ion storage capability due to their electric double layer capacitance (EDLC) energy storage mechanism that is restricted by specific surface area and thickness of electric double layer (EDL). Here, we report a universal surface charge modulation strategy to effectively enhance the capacitance of carbon materials by decreasing the thickness of EDL. Amino groups with lone pair electrons were chosen to increase the surface charge density and enhanced the interaction between carbon electrode and Zn ions, thus effectively compacting the EDL.

Unshared Pair Electrons of Zincophilic Lewis Base Enable Long-life Zn Anodes under "Three High" Conditions.

The hydrogen evolution and dendrite issues are the notorious culprits of the limited lifespan and Coulombic efficiency (CE) of Zn anodes, particularly at harsh test conditions. Herein, considering the Lewis acidic feature of Zn , abundant unshared pair electrons of zincophilic Lewis bases are proposed as decent electrolyte additives to stabilize Zn anodes at "Three High" conditions (high depth of discharge, high areal capacity and high current). The unshared pair electrons can remove H O from Zn solvated sheaths and confine the activity of H O by breaking its hydrogen bonding network.

Defect Engineering Triggers Exceptional Sonodynamic Activity of Manganese Oxide Nanoparticles for Cancer Therapy.

Sonodynamic therapy (SDT) has received increasing interest in cancer treatment, but its clinical application is still constrained by the low activity of sonosensitizers and their unclear mechanism. Herein, a kind of oxygen-deficient manganese oxide (MnO) nanoparticles with greatly enhanced sonodynamic activity and good biocompatibility is developed as an advanced sonosensitizer. The introduced oxygen defects can remarkably enhance the electrical conductivity of manganese oxide (MnO) nanoparticles and serve as charge trapping sites to prohibit the electron-hole pair recombination upon ultrasound (US) irradiation.

Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice.

CaMK4 has an important function in autoimmune diseases, and the contribution of CaMK4 in psoriasis remains obscure. Here, we show that CaMK4 expression is significantly increased in psoriatic lesional skin from psoriasis patients compared to healthy human skin as well as inflamed skin from an imiquimod (IMQ)-induced mouse model of psoriasis compared to healthy mouse skin. Camk4-deficient (Camk4) mice treated with IMQ exhibit reduced severity of psoriasis compared to wild-type (WT) mice.

Optimization of the vancomycin administration regimen by clinical pharmacists based on a population pharmacokinetics model: a prospective interventional study.

In vancomycin treatment, the rates of correct blood sampling and initial trough concentrations within the target range are very low. Studies of interventions by clinical pharmacists based on population pharmacokinetics (PPK) models are limited. This study aimed to evaluate the intervention effect of clinical pharmacist-mediated optimization of the vancomycin administration regimen based on a PPK model.