Immunogenicity and safety of an investigational quadrivalent meningococcal conjugate vaccine administered as a booster dose in children vaccinated against meningococcal disease 3 years earlier as toddlers: A Phase III, open-label, multi-center study.

Booster doses of meningococcal conjugate vaccines induce long-term protection against invasive meningococcal disease. We evaluated the immunogenicity and safety of a booster dose of MenACYW-TT in pre-school children who were primed 3 years earlier with MenACYW-TT or MCV4-TT (Nimenrix®). In this Phase III, open-label, multi-center study (NCT03476135), children (4-5 years old), who received a primary dose of MenACYW-TT or MCV4-TT as toddlers in a previous study, received a booster dose of MenACYW-TT.

Additive interaction between potentially modifiable risk factors and ethnicity among individuals in the Han, Tujia and Miao populations with first-ever ischaemic stroke.

Background: As a country with one-fifth of the global population, China has experienced explosive growth in ischaemic stroke (IS) burden with significant ethnic and geographic disparities. The aim of this study was to examine the differences in potentially modifiable risk factors for ischaemic stroke among the Han population and two ethnic minorities (Tujia and Miao).

Methods: A case-control study was conducted with 324 cases of first-ever ischaemic stroke from the hospitals of the Xiangxi Tujia and Miao Autonomous Prefecture and 394 controls from communities covering the same area between May 1, 2018, and April 30, 2019.

RNA methyltransferase NSUN2 promotes hypopharyngeal squamous cell carcinoma proliferation and migration by enhancing TEAD1 expression in an mC-dependent manner.

RNA methyltransferase NSUN2 is involved in cell proliferation and invasion in a variety of tumors. However, the expression, function, and mechanism of NSUN2 in hypopharyngeal squamous cell carcinoma (HPSCC) remains unknown. We used a bioinformatics database, polymerase chain reaction, cell culture and transfection, immunohistochemistry, cell proliferation assay, wound healing experiments, transwell assays, western blotting, RNA-seq detection, dual-luciferase reporter assay, in vivo experiments, and a dot blot assay to evaluate the role of NSUN2 in HPSCC.

Distal Arterialized Venous Supercharging Improves Perfusion and Survival in an Extended Dorsal Three-Perforasome Perforator Flap Rat Model.

Background: Perforator flaps are commonly applied for a variety of skin defects. Many strategies (e.g.

[CT Characteristics of Consolidation Type of Pulmonary Cryptococcosis in Immunocompetent Patients].

Objective To analyze the CT characteristics of consolidation type of pulmonary cryptococcosis in immunocompetent patients,and thus improve the diagnosis of this disease. Methods A total of 20 cases with consolidation-type pulmonary cryptococcosis confirmed by pathological examinations were studied.Each patient underwent breath-hold multislice spiral CT,and 10 patients underwent contrast enhanced CT.

Targeting TFE3 Protects Against Lysosomal Malfunction-Induced Pyroptosis in Random Skin Flaps via ROS Elimination.

Increasing evidence indicates that pyroptosis, a new type of programmed cell death, may participate in random flap necrosis and play an important role. ROS-induced lysosome malfunction is an important inducement of pyroptosis. Transcription factor E3 (TFE3) exerts a decisive effect in oxidative metabolism and lysosomal homeostasis.

Phenotypic screen identifies calcineurin-sparing FK506 analogs as BMP potentiators for treatment of acute kidney injury.

Acute kidney injury (AKI) is a life-threatening disease with no known curative or preventive therapies. Data from multiple animal models and human studies have linked dysregulation of bone morphogenetic protein (BMP) signaling to AKI. Small molecules that potentiate endogenous BMP signaling should have a beneficial effect in AKI.

Liraglutide, a TFEB-Mediated Autophagy Agonist, Promotes the Viability of Random-Pattern Skin Flaps.

Random skin flaps are commonly used in reconstruction surgery. However, distal necrosis of the skin flap remains a difficult problem in plastic surgery. Many studies have shown that activation of autophagy is an important means of maintaining cell homeostasis and can improve the survival rate of flaps.

SAF-248, a novel PI3Kδ-selective inhibitor, potently suppresses the growth of diffuse large B-cell lymphoma.

PI3Kδ is expressed predominately in leukocytes and overexpressed in B-cell-related malignances. PI3Kδ has been validated as a promising target for cancer therapy, and specific PI3Kδ inhibitors were approved for clinical practice. However, the substantial toxicity and relatively low efficacy as a monotherapy in diffuse large B-cell lymphoma (DLBCL) limit their clinical use.

Thermosensitive quaternized chitosan hydrogel scaffolds promote neural differentiation in bone marrow mesenchymal stem cells and functional recovery in a rat spinal cord injury model.

A thermosensitive quaternary ammonium chloride chitosan/β-glycerophosphate (HACC/β-GP) hydrogel scaffold combined with bone marrow mesenchymal stem cells (BMSCs) transfected with an adenovirus containing the glial cell-derived neurotrophic factor (GDNF) gene (Ad-rGDNF) was applied to spinal cord injury (SCI) repair. The BMSCs from rats were transfected with Ad-rGDNF, resulting in the expression of GDNF mRNA in the BMSCs increasing and their spontaneous differentiation into neural-like cells expressing neural markers such as NF-200 and GFAP. After incubation with HACC/β-GP hydrogel scaffolds for 2 weeks, neuronal differentiation of the BMSCs was confirmed using immunofluorescence (IF), and the expression of GDNF by the BMSCs was detected by Western blot at different time points.

A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer's dementia.

Background: New therapies are urgently needed for Alzheimer's disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China.

Chemically Modified SDF-1α mRNA Promotes Random Flap Survival by Activating the SDF-1α/CXCR4 Axis in Rats.

Random skin flaps are frequently applied in plastic and reconstructive surgery for patients suffering from soft tissue defects caused by congenital deformities, trauma and tumor resection. However, ischemia and necrosis in distal parts of random skin flaps remains a common challenge that limits the clinical application of this procedure. Recently, chemically modified mRNA (modRNA) was found to have great therapeutic potential.

Discovery of novel ceramide analogs with favorable pharmacokinetic properties and combination with AKT inhibitor against colon cancer.

Ceramides have emerged as potential therapeutic option with novel mechanism to affect the proliferation, differentiation, senescence, and apoptosis of cancer cells through regulation of multiple signal transduction. Aiming at the improvement of the apoptosis activity and pharmacokinetic profiles of ceramides, a novel series of ceramide analogs were developed through structure simplification and conformation restriction. Among them, compound 12 bearing an alkoxyl naphthyl motif, with favorable rat pharmacokinetic properties, showed better anti-proliferative activity against various colon cancer cells (IC ∼20 μM) than other ceramide analogues, as well as the synergistic effect combined with AKT inhibitor MK2206.

Factors associated with delayed viral shedding in COVID-19 infected patients: A retrospective small-scale study.

Background: The outbreak of COVID-19 has caused ever-increasing attention and public panic all over the world. Until now, data are limited about the risk factors to virus shedding in COVID-19 infected patients.

Methods: In this retrospective study, data were collected from 87 patients hospitalized with COVID-19 infection in Suzhou.

Novel green chitosan-pectin gel beads for the removal of Cu(II), Cd(II), Hg(II) and Pb(II) from aqueous solution.

Chitosan-pectin gel beads (CPBs) were synthesized via a facile and green method and applied to remove heavy metals from aqueous solution. The structural characteristics of CPBs were investigated by SEM and FTIR, the mechanical strength of CPBs was measured by Texture Analyzer and the stability of CPBs was evaluated in acidic solution. To study the adsorption characteristics, the effect of pH, contact time, initial heavy metals concentration, temperature, adsorption mechanism and regeneration were systematically investigated.

Nitrogen forms and metabolism affect plant defence to foliar and root pathogens in tomato.

Nitrogen (N) influences a myriad of physiological processes while its effects on plant defences and the underlying mechanisms are largely unknown. Here, the interaction between tomato and pathogens was examined under four N regimes (sole NO or mixed NO /NH of total 1 and 7 mM N, denoting low and high N regimes, respectively) followed by inoculation with two bacterial pathogens, Pseudomonas syringae and Ralstonia solanacearum. Tomato immunity against both pathogens was generally higher under low N as well as NO as the sole N source.

Idiopathic mesenteric phlebosclerosis: clinical and CT imaging characteristics.

Background: The aim of our study was to evaluate the clinical characteristics and computed tomography (CT) imaging findings of idiopathic mesenteric phlebosclerosis (IMP).

Methods: From January 2013 to May 2019, the clinical data of 10 patients diagnosed with IMP were analyzed retrospectively. Computed tomography angiography (CTA) and colonoscopy were performed in all 10 patients.

Design, Synthesis, and Biological Evaluation of IRAK4-Targeting PROTACs.

Interleukin-1 receptor associated kinase 4 (IRAK4) is a promising therapeutic target for diffuse large B-cell lymphoma driven by MYD88 L265P mutant, acting both as a kinase and a scaffolding protein for downstream signaling molecules. While previous efforts to modulate IRAK4 activity with kinase inhibitors alone displayed moderate efficacy, protein degradation may offer a solution to blocking both IRAK4 kinase activity and scaffolding capabilities. To this end, the potent IRAK4 degrader was discovered, and it effectively inhibited the activation of downstream NF-κB signaling and outperformed the parent compound .

Characterization of Feedback Neurons in the High-Level Visual Cortical Areas That Project Directly to the Primary Visual Cortex in the Cat.

Previous studies indicate that top-down influence plays a critical role in visual information processing and perceptual detection. However, the substrate that carries top-down influence remains poorly understood. Using a combined technique of retrograde neuronal tracing and immunofluorescent double labeling, we characterized the distribution and cell type of feedback neurons in cat's high-level visual cortical areas that send direct connections to the primary visual cortex (V1: area 17).

Dual fluoroscopic imaging and CT-based finite element modelling to estimate forces and stresses of grafts in anatomical single-bundle ACL reconstruction with different femoral tunnels.

Purpose: Little is known about the in vivo forces and stresses on grafts used in anterior cruciate ligament (ACL) reconstruction. The aims of this study were to evaluate and compare the forces and stresses on grafts used in anatomical single-bundle ACL reconstruction at different locations of the femoral footprint (anterior vs middle vs posterior; high vs middle vs low) during a lunge motion.

Methods: Establish subject-specific finite element models with different graft's tunnel loci to represent the primary ACL reconstructions.

MRI analysis and surgical treatment of Wassel Type IV duplicated thumbs.

We present the MRI findings for 39 Wassel Type IV duplicated thumbs in 38 patients. We found that MRI revealed the morphology of the cartilaginous connection between the thumb anlages and the location of the deviation corresponding to the classification of Horii, which allowed precise preoperative planning of corrective osteotomies. All 39 thumbs were available for follow-up after surgical reconstruction at a mean of 29 months (range 25 to 39).

Adaptive resistance to PI3Kα-selective inhibitor CYH33 is mediated by genomic and transcriptomic alterations in ESCC cells.

Phosphoinositide-3 kinase alpha-specific inhibitors (PI3Kαi) displayed promising potential for the treatment of esophageal squamous cell carcinoma (ESCC) with frequent activation in PI3K signaling. However, acquired resistance is likely to develop and limit the efficacy of PI3Kαi like other targeted therapies. To identify genomic adaptation to PI3Kαi, we applied whole-genome sequencing and detected gene mutation and amplification in four lines of ESCC cells established with adapted resistance to a novel PI3Kαi CYH33.

Quantitative proteomic analysis of Xanthoceras sorbifolium Bunge seedlings in response to drought and heat stress.

Yellowhorn (Xanthoceras sorbifolium Bunge) is a woody oil species that is widely distributed in northwestern China. To investigate the molecular mechanisms underlying the drought and heat tolerance response of yellowhorn seedlings, changes in protein abundance were analyzed via comparative proteomics. Drought and heat treatment of seedlings was applied in growth chamber, and the leaves were harvested after 7 days of treatment.

A novel tricyclic BTK inhibitor suppresses B cell responses and osteoclastic bone erosion in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by joint leukocyte infiltration, synovial inflammation and bone damage result from osteoclastogenesis. Bruton's tyrosine kinase (BTK) is a key regulator of B cell receptor (BCR) and Fc gamma receptor (FcγR) signaling involved in the pathobiology of RA and other autoimmune disorders. SOMCL-17-016 is a potent and selective tricyclic BTK inhibitor, structurally distinct from other known BTK inhibitors.