Effect of periodic nursing interventions on improving compliance behavior and health status in long-term Hemodialysis patients.

Objective: To investigate the effect of periodic nursing interventions on improving compliance behavior and health status in long-term hemodialysis patients.

Method: This was retrospective study. A total of 88 patients on long-term hemodialysis admitted to Qinhuangdao Haigang Hospital from January 2022 to April 2023 were randomly divided into the control group and the intervention group, who received routine hemodialysis nursing and periodic nursing interventions, respectively.

Medical image analysis using improved SAM-Med2D: segmentation and classification perspectives.

Recently emerged SAM-Med2D represents a state-of-the-art advancement in medical image segmentation. Through fine-tuning the Large Visual Model, Segment Anything Model (SAM), on extensive medical datasets, it has achieved impressive results in cross-modal medical image segmentation. However, its reliance on interactive prompts may restrict its applicability under specific conditions.

Discovery of spiro amide SHR902275: A potent, selective, and efficacious RAF inhibitor targeting RAS mutant cancers.

The RAS-RAF-MEK-ERK signaling pathway plays a key role to regulate multiple cellular functions. Acquired resistance to the first-generation RAF inhibitors that only targeted the bRAF mutation prompted the need for a new generation of RAF inhibitors to target cancers bearing mutant RAS and wild type RAF activity by inhibition of paradoxical activation. Starting from the company's previously reported RAF inhibitor 1, extensive drug potency and drug-like properties optimizations led to the discovery of molecule 33 (SHR902275) with greatly improved in vitro potency and solubility.

Discovery of a novel RORγ antagonist with skin-restricted exposure for topical treatment of mild to moderate psoriasis.

Clinical success of IL-17/IL-23 pathway biologics for the treatment of moderate to severe psoriasis suggests that targeting RORγt, a master regulator for the proliferation and function of Th17 cells, could be an effective alternative. However, oral RORγ antagonists (VTP43742, TAK828) with high systemic exposure showed toxicity in phase I/II clinical trials and terminated development. To alleviate the potential safety concerns, identifying compounds with skin-restricted exposure amenable for topical use is of great interest.

Discovery of SHR1653, a Highly Potent and Selective OTR Antagonist with Improved Blood-Brain Barrier Penetration.

The oxytocin receptor (OTR) plays a major role in the control of male sexual responses. Antagonists of the OTR have been reported to inhibit ejaculation in animal models and serve as a potential treatment for premature ejaculation (PE). Herein, we describe a novel scaffold featuring an aryl substituted 3-azabicyclo [3.

A Secure and High-Fidelity Live Animal Model for Off-Pump Coronary Bypass Surgery Training.

Objective: Existing simulators for off-pump coronary artery (CA) bypass grafting training are unable to provide cardiac surgery residents all necessary skills they need entering the operation room. In this study, we introduced a secure and high-fidelity live animal model to supplement the in vitro simulators for off-pump CA bypass grafting training.

Design: The left internal thoracic artery (ITA) of 3 Chinese miniature pigs was grafted to the left anterior descending CA using an end-to-side anastomosis.

Transapical implantation of a self-expandable aortic valve prosthesis utilizing a novel designed positioning element.

Objectives: To evaluate a new transapical system which utilizes a novel designed positioning element and a two-step positioning mechanism for easy and accurate implantation of transcatheter valves.

Background: Transcatheter aortic valve implantation is an important treatment option for non-surgical patients with severe aortic stenosis. However, accurate placement of the transcatheter valve remains challenging.

Optimized protein kinase Cθ (PKCθ) inhibitors reveal only modest anti-inflammatory efficacy in a rodent model of arthritis.

We previously demonstrated that selective inhibition of protein kinase Cθ (PKCθ) with triazinone 1 resulted in dose-dependent reduction of paw swelling in a mouse model of arthritis.1,2 However, a high concentration was required for efficacy, thus providing only a minimal safety window. Herein we describe a strategy to deliver safer compounds based on the hypothesis that optimization of potency in concert with good oral pharmacokinetic (PK) properties would enable in vivo efficacy at reduced exposures, resulting in an improved safety window.

LCK: a new biomarker candidate for the early diagnosis of acute myocardial infarction.

Acute myocardial infarction (AMI) is one of the most common cardiovascular emergencies, of which the molecular pathogenesis is still not fully understood. This study aimed to explore the differentially expressed genes (DEGs) and then identify the critical genes in AMI thus screening out potential biomarkers for the early diagnosis of this serious heart disease. The gene expression data of AMI patients (GSE19339) were downloaded from gene expression omnibus database.

Neural progenitor cells derived from adult bone marrow mesenchymal stem cells promote neuronal regeneration.

Aim: It is well known that neural stem/progenitor cells (NS/PC) are an ideal cell type for the treatment of central nervous system (CNS) disease. However, ethical problems have severely hampered fetal NS/PC from being widely used as a source for stem cell therapy. Recently, it has been demonstrated that autologous bone marrow mesenchymal stem cells (BMSC) can transdifferentiate into neural progenitor cells (NPC).

Mitochondrial and Plasma Membrane Citrate Transporters: Discovery of Selective Inhibitors and Application to Structure/Function Analysis.

Cytoplasmic citrate is the prime carbon source for fatty acid, triacylglycerol, and cholesterol biosyntheses, and also regulates glucose metabolism via its allosteric inhibition of phosphofructokinase. It originates either via the efflux of citrate from the mitochondrial matrix on the inner membrane citrate transport protein (CTP) or via the influx of extracellular citrate on the plasma membrane citrate transporter (PMCT). Despite their common substrate, the two transport proteins share little sequence similarity and they transport citrate via fundamentally different mechanisms.

The yeast mitochondrial citrate transport protein: molecular determinants of its substrate specificity.

The objective of this study was to identify the role of individual amino acid residues in determining the substrate specificity of the yeast mitochondrial citrate transport protein (CTP). Previously, we showed that the CTP contains at least two substrate-binding sites. In this study, utilizing the overexpressed, single-Cys CTP-binding site variants that were functionally reconstituted in liposomes, we examined CTP specificity from both its external and internal surfaces.

Probing the effect of transport inhibitors on the conformation of the mitochondrial citrate transport protein via a site-directed spin labeling approach.

The present investigation utilized the site-directed spin labeling method of electron paramagnetic resonance (EPR) spectroscopy to identify the effect of citrate, the natural ligand, and transport inhibitors on the conformation of the yeast mitochondrial citrate transport protein (CTP) reconstituted in liposomal vesicles. Spin label was placed at six different locations within the CTP in order to monitor conformational changes that occurred near each of the transporter's two substrate binding sites, as well as at more distant domains within the CTP architecture. We observed that citrate caused little change in the EPR spectra.

Inhibitors of the mitochondrial citrate transport protein: validation of the role of substrate binding residues and discovery of the first purely competitive inhibitor.

The mitochondrial citrate transport protein (CTP) is critical to energy metabolism in eukaryotic cells. We demonstrate that 1,2,3-benzenetricarboxylate (BTC), the classic and defining inhibitor of the mitochondrial CTP, is a mixed inhibitor of the reconstituted Cys-less CTP, with a strong competitive component [i.e.

The yeast mitochondrial citrate transport protein: identification of the Lysine residues responsible for inhibition mediated by Pyridoxal 5'-phosphate.

The present investigation identifies the molecular basis for the well-documented inhibition of the mitochondrial inner membrane citrate transport protein (CTP) function by the lysine-selective reagent pyridoxal 5'-phosphate. Kinetic analysis indicates that PLP is a linear mixed inhibitor of the Cys-less CTP, with a predominantly competitive component. We have previously concluded that the CTP contains at least two substrate binding sites which are located at increasing depths within the substrate translocation pathway and which contain key lysine residues.

Identification of the substrate binding sites within the yeast mitochondrial citrate transport protein.

The objective of the present investigation was to identify the substrate binding site(s) within the yeast mitochondrial citrate transport protein (CTP). Our strategy involved kinetically characterizing 30 single-Cys CTP mutants that we had previously constructed based on their hypothesized importance in the structure-based mechanism of this carrier. As part of these studies, a modified transport assay was developed that permitted, for the first time, the accurate determination of K(m) values that were elevated >100-fold compared with the Cys-less control value.