A novel stoploss mutation CYB5R3 c.906A>G(p.*302Trpext*42) involved in the pathogenesis of hereditary methemoglobinemia.

Recessive congenital methemoglobinemia (RCM) is a hereditary autosomal disorder with an extremely low incidence rate. Here, we report a case of methemoglobinemia type I in a patient with congenital persistent cyanosis. The condition was attributed to a novel compound heterozygous mutation in CYB5R3, characterized by elevated methemoglobin levels (13.

study of p.Ala275Pro mutant causing alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism.

Introduction: We previously reported that ATP1A3 c.823G>C (p.Ala275Pro) mutant causes varying phenotypes of alternative hemiplegia of childhood and rapid-onset dystonia-parkinsonism in the same family.

A rare concurrence of acute tubular necrosis and chronic glomerular sclerosis in a patient with wasp stings.

Wasp venom injections from wasp stings can damage several organs, most commonly the kidneys. Despite literature evidence, wasp sting-induced acute kidney injury (AKI) is rare and involves complex pathophysiological processes. While acute tubular necrosis (ATN) is the most prevalent histological result of wasp sting-induced AKI, uncommon combinations of chronic renal lesions have been described, alerting us to the patient's underlying illness.

A novel splicing mutation DNAH5 c.13,338 + 5G > C is involved in the pathogenesis of primary ciliary dyskinesia in a family with primary familial brain calcification.

Background: Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease characterized by recurrent respiratory infections. In clinical manifestations, DNAH5 (NM_001361.3) is one of the recessive pathogenic genes.

Integrating single-cell and bulk RNA sequencing reveals CK19 + cancer stem cells and their specific SPP1 + tumor-associated macrophage niche in HBV-related hepatocellular carcinoma.

Purpose: Cytokeratin 19-positive cancer stem cells (CK19 + CSCs) and their tumor-associated macrophages (TAMs) have not been fully explored yet in the hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

Experimental Design: Single-cell RNA sequencing was performed on the viable cells obtained from 11 treatment-naïve HBV-associated HCC patients, including 8 CK19 + patients, to elucidate their transcriptomic landscape, CK19 + CSC heterogeneity, and immune microenvironment. Two in-house primary HCC cohorts (96 cases-related HBV and 89 cases with recurrence), TCGA external cohort, and in vitro and in vivo experiments were used to validate the results.

Clinical implications and biological features of a novel postoperative recurrent HCC classification: A multi-centre study.

Background & Aims: The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine.

Methods: A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178).

Gelatin methacryloyl hydrogels functionalized with endothelin-1 for angiogenesis and full-thickness wound healing.

Natural polymer hydrogels are widely used as wound dressings, but they do not have enough bioactivity to accelerate angiogenesis and re-epithelialization. Herein, a therapeutic system was firstly constructed in which endothelin-1 (ET-1), as an endogenous vasoconstrictor peptide, was embedded in a photo-crosslinking gelatin methacryloyl (GelMA) hydrogel for full-thickness wound healing. The multifunctional GelMA-ET-1 hydrogels contained the arginine-glycine-aspartate (RGD) motifs of gelatin that provided adhesive sites for cell proliferation and migration.

Dural sac cross-sectional area is a highly effective parameter for spinal anesthesia in geriatric patients undergoing transurethral resection of the prostate: a prospective, double blinded, randomized study.

Background: Spinal anesthesia is optimal choice for transurethral resection of the prostate (TURP), but the sensory block should not cross the T10 level. With advancing age, the sensory blockade level increases after spinal injection in some patients with spinal canal stenosis. We optimize the dose of spinal anesthesia according to the decreased ratio of the dural sac cross-sectional area (DSCSA), the purpose of this study is to hypothesis that if DSCSA is an effective parameter to modify the dosage of spinal anesthetics to achieve a T10 blockade in geriatric patients undergoing TURP.

Reply to Comments on 'A functional polymorphism rs10830963 in melatonin receptor 1B associated with the risk of gestational diabetes mellitus'.

Th authors of 'A functional polymorphism rs10830963 in melatonin receptor 1B associated with the risk of gestational diabetes mellitus' (Bioscience Reports (2019) 39, 12) have written a reply in response to the correspondence piece by Rosta et al. (Bioscience Reports (2020) 40, 2).

In Vitro Metabolism by Aldehyde Oxidase Leads to Poor Pharmacokinetic Profile in Rats for c-Met Inhibitor MET401.

Background And Objectives: MET401 is a potent and selective c-Met inhibitor with a novel triazolopyrimidine scaffold. The aim of this study was to determine the pharmacokinetic profile of MET401 in preclinical species, and to identify the metabolic soft spot and enzyme involved, in order to help medicinal chemists to modify the compound to improve the pharmacokinetic profile.

Methods: A metabolite identification study was performed in different liver fractions from various species.

Association between polymorphisms in MicroRNA target sites of RAD51D genes and risk of hepatocellular carcinoma.

RAD51D (RAD51L3) is a member of the RAD51 gene family which plays important roles in maintaining genomic stability and preventing DNA damage. This study is aimed to investigate the associations between RAD51D polymorphisms and the hereditary susceptibility of hepatocellular carcinoma (HCC). In this study we conducted a hospital-based case-control study including 805 cases (HCC patients) and 846 controls (nontumor patients) in Guangxi, China.

Structure-Based Optimization of Multifunctional Agonists for Opioid and Neuropeptide FF Receptors with Potent Nontolerance Forming Analgesic Activities.

The opioid and neuropeptide FF pharmacophore-containing chimeric peptide 0 (BN-9) was recently developed and produced potent nontolerance forming analgesia. In this study, 11 analogues of 0 were designed and synthesized. An in vitro cAMP assay demonstrated that these analogues behaved as multifunctional agonists at both opioid and NPFF receptors.

Activation of NPFF receptor stimulates neurite outgrowth in Neuro 2A cells through activation of ERK signaling pathway.

Neurite outgrowth is an important process in neural regeneration and plasticity, especially after neural injury, and recent evidence indicates that several G protein-coupled receptors play an important role in neurite outgrowth. The neuropeptide (NP)FF system contains two G protein-coupled receptors, NPFF and NPFF receptors, which are mainly distributed in the central nervous system. The aim of the present study was to determine whether the NPFF system is involved in neurite outgrowth in Neuro 2A cells.

Pharmacological characterization of EN-9, a novel chimeric peptide of endomorphin-2 and neuropeptide FF that produces potent antinociceptive activity and limited tolerance.

Mounting evidences indicate the functional interactions between neuropeptide FF (NPFF) and opioids, including the endogenous opioids. In the present work, EN-9, a chimeric peptide containing the functional domains of the endogenous opioid endomorphin-2 (EM-2) and NPFF, was synthesized and pharmacologically characterized. In vitro cAMP assay demonstrated that EN-9 was a multifunctional agonist of κ-opioid, NPFF1 and NPFF2 receptors.

The effects of preweaning manganese exposure on spatial learning ability and p-CaMKIIα level in the hippocampus.

Background: The effects and mechanisms of preweaning Manganese (Mn) exposure on cognitive dysfunction remain unclear.

Objective: This study evaluated the effects of preweaning Mn exposure on spatial learning and memory as well as the protein expression of CaMKIIα and p-CaMKIIα.

Methods: We treated neonate rats with Mn(2+) doses of 0 (control group), 10, 20 and 30mg of Mn(2+) per kg body weight (Mn-exposed groups) over postnatal day (PND) 1-21 by intraperitoneal injection.

Effects of neuropeptide FF and related peptides on the antinociceptive activities of VD-hemopressin(α) in naive and cannabinoid-tolerant mice.

Neuropeptide FF (NPFF) system has recently been reported to modulate cannabinoid-induced antinociception. The aim of the present study was to further investigate the roles of NPFF system in the antinociceptive effects induced by intracerebroventricular (i.c.

Combined effects of six cytokine gene polymorphisms and SNP-SNP interactions on hepatocellular carcinoma risk in Southern Guangxi, China.

Cytokine gene single nucleotide polymorphisms (SNPs) are involved in the genesis and progression of hepatocellular carcinoma (HCC). We hypothesized that combined effects of cytokine gene SNPs and SNP-SNP interactions are associated with HCC risk. Six SNPs in cytokine genes (IL-2, IFN-γ, IL-1β, IL-6, and IL-10) were genotyped in a study of 720 Chinese HCC cases and 784 cancer-free controls.