What They Gain Depends on What They Do: An Exploratory Empirical Research on Effective Use of Mobile Healthcare Applications

Mobile healthcare application receives widespread attention, although it has advanced technology and user-friendly design, when users don’t use it effectively, it seems worthless. Research mainly focus on technology improvement. But how to improve user behavior to match the technology is another essential factor for facilitating effective use from managerial perspective. We introduced the task technology fit theory to explain the mechanism when user using the applications. We added perceived e-health literacy as moderator variable, considering the user characteristic and medical environment. The data was collected from student samples of two schools (medical and non-medical related universities), totally 178 valid samples. Our research indicates adaptation and learning behavior have significantly positive impact on the efficiency use and effectiveness use. The perceived e-health literacy only has significant moderator effect on learning behavior. Our study provides practical implications for both software providers and users to achieve effective use of mobile healthcare applications

XAF1 expression and regulatory effects of somatostatin on XAF1 in prostate cancer cells

<p>Abstract</p> <p>Background</p> <p>Somatostatin prevents cell proliferation by inducing apoptosis. Downregulation of the <it>XAF1 </it>transcript may occur during the development of prostate cancer. It is interesting to evaluate the potential regulatory effects of somatostatin on <it>XAF1 </it>expression during the development of prostate cancer cells.</p> <p>Methods</p> <p><it>XAF1 </it>mRNA and protein expression in human prostate epithelial cells RWPE-1, androgen dependent prostate cancer LNCaP, and androgen independent DU145 and PC3 cells were evaluated using RT-PCR and Western blot. The regulation of <it>XAF1 </it>mRNA and protein expression by somatostatin and its analogue Octreotide was evaluated.</p> <p>Results</p> <p>Substantial levels of <it>XAF1 </it>mRNA and proteins were detected in RWPE-1 cells, whereas prostate cancer cells LNCaP, DU145 and PC3 exhibited lower <it>XAF1 </it>expression. Somatostatin and Octreotide up-regulated <it>XAF1 </it>mRNA and protein expression in all prostate cancer cell lines.</p> <p>Conclusions</p> <p><it>XAF1 </it>down-regulation may contribute to the prostate cancer development. The enhanced <it>XAF1 </it>expression by somatostatin indicates a promising strategy for prostate cancer therapy.</p

Transient p53 suppression increases reprogramming of human fibroblasts without affecting apoptosis and DNA damage

The discovery of human-induced pluripotent stem cells (iPSCs) has sparked great interest in the potential treatment of patients with their own in vitro differentiated cells. Recently, knockout of the Tumor Protein 53 (p53) gene was reported to facilitate reprogramming but unfortunately also led to genomic instability. Here, we report that transient suppression of p53 during nonintegrative reprogramming of human fibroblasts leads to a significant increase in expression of pluripotency markers and overall number of iPSC colonies, due to downstream suppression of p21, without affecting apoptosis and DNA damage. Stable iPSC lines generated with or without p53 suppression showed comparable expression of pluripotency markers and methylation patterns, displayed normal karyotypes, contained between 0 and 5 genomic copy number variations and produced functional neurons in vitro. In conclusion, transient p53 suppression increases reprogramming efficiency without affecting genomic stability, rendering the method suitable for in vitro mechanistic studies with the possibility for future clinical translation

Functional and structural analysis of a novel splice site HMBS variant in a Chinese AIP patient

Background: Acute intermittent porphyria (AIP) is a rare metabolic disorder that results from mutations in the gene encoding hydroxymethylbilane synthase (HMBS), an enzyme involved in heme biosynthesis. AIP follows an autosomal dominant inheritance pattern, but most carriers are asymptomatic. The clinical manifestations of AIP include acute attacks of abdominal pain and neuropsychiatric disturbances. The pathogenicity of novel HMBS variants identified in Chinese patients has not been well established.Objective: The article aims to identify the pathogenic mutation in an AIP patient and prove its pathogenicity through in vitro experiments.Methods: A 22-year-old female diagnosed with AIP participated in the study. Variant screening of her HMBS gene was carried out through Sanger sequencing. To ascertain the consequences of the newly discovered variant, we conducted in vitro experimentation targeting HMBS gene expression and enzymatic function. Additionally, protein structure analysis was performed. Cycloheximide treatment and UPF1-specific siRNA knockdown were employed to assess the impact of the mutation on the mechanism of non-sense-mediated mRNA decay (NMD).Results: A novel splice site variant in the HMBS gene (c.648_651+1delCCAGG) was detected in the patient, which caused aberrant mRNA splicing. In vitro experiments demonstrated that this variant significantly decreased the expression of HMBS. Further investigation confirmed that this decrease was due to NMD. Additionally, structural analysis indicated that this variant would destabilize the HMBS protein and impair its catalytic activity. To gain a comprehensive understanding of HMBS mutations in the context of AIP, we conducted a literature search on PubMed using the keywords ‘HMBS’ and ‘Acute intermittent porphyria’ from 2013 to 2023. This search yielded 19 clinical case reports written in English, which collectively described 220 HMBS gene mutations worldwide.Conclusion: The study identified and proved the pathogenicity of a novel splice site HMBS variant for the first time. Our results elucidated the pathological mechanism by which this mutation causes AIP through reducing HMBS expression and activity. These findings provide theoretical guidance for the diagnosis, treatment and genetic counseling of AIP patients

Research on influencing factors and remedial measures of coal seam water blocking effect

Coalbed methane development primarily relies on hydraulic fracturing and drainage gas extraction processes. The intrusion of external fluids and long-term drainage and extraction contribute to the water blocking effect, which becomes one of the crucial factors affecting production capacity. In this study, the coal reservoir of a certain coalbed methane in Hancheng, Shaanxi Province, was selected as the research object. The experimental method was employed to comprehensively evaluate the correlation between factors such as coal sample moisture content, permeability, porosity, properties of external liquids, and water blocking damage. The results indicated that there was a positive correlation between coal sample moisture content, liquid surface tension, and water blocking damage. On the other hand, coal sample pore permeability characteristics, liquid contact angle with rock samples, and water blocking damage showed a negative correlation. Building upon the aforementioned research, an investigation into remedial measures for water blocking damage was conducted. Additionally, a chemical treatment study using the compound surfactant system JSS-1 as a water-blocking agent was performed to manage the water blocking effect. The results demonstrated that JSS-1 as a water-blocking agent significantly reduced the surface tension of the wellbore fluid and improved its wetting behavior on the coal-rock surface. The laboratory experiments confirmed the capability of JSS-1 in managing the water blocking effect

Segmental Membranous Glomerulopathy in Adults

Introduction: The clinicopathological features of segmental membranous glomerulopathy (SMGN) have not been well characterized. The aim of this study was to investigate the prevalence and clinicopathological features of SMGN in adults. Methods: Adult patients with biopsy-confirmed SMGN in the native kidney at our center between January 2017 to September 2020 were identified. The clinicopathological features of SMGN were collected. The glomerular deposition of IgG subclasses, M-type phospholipase A2 receptor 1 (PLA2R), thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) were tested. Clinical and pathologic features were comparable between NELL1-positive and NELL1-negative SMGN. Results: A total of 167 patients with biopsy-proven SMGN were enrolled. During the same period, 32,640 (33.0%) out of 98,939 renal biopsies were diagnosed with membranous nephropathy (MN) in adults. SMGN accounted for 0.17% of total kidney biopsies and 0.51% of MN in adults. One hundred and fifty (89.8%) cases were isolated SMGN and 17 (10.2%) cases were complicated with other kidney disease. Clinically, the median age of isolated SMGN patients was 41.5 years, with female (74%) predominance, and 33.1% had full nephrotic syndrome. Pathologically, IgG1 was the dominant subclass (92.5%), followed by IgG4 (45.0%). PLA2R and THSD7A staining were done in 142 and 136 isolated SMGN cases, respectively. In which, all the cases showed negative. NELL1 staining was done in 135 isolated SMGN cases, 58 cases (43.0%) showed positive. Fifty-eight patients (41.1%) had diffuse (≥90%) foot process effacement, 119 patients (83.8%) had either stage I (38.0%) or stage II (45.8%) membranous alterations in patients with SMGN. Most patients with NELL1-positive SMGN were female. Patients with NELL1-positive SMGN were more likely with lower prevalence of full nephrotic syndrome than NELL1-negative SMGN. Conclusions: SMGN is a relatively rare pathological type. Majority of patients with isolated SMGN were female, with a median age of 41.5 years, 33.1% had full nephrotic syndrome, absence of PLA2R and THSD7A, 43.0% with NELL1-positive, and mainly stage I or II MN (83.8%). NELL1 is the major target antigen of SMGN in adults

An atlas of DNA methylomes in porcine adipose and muscle tissues

It is evident that epigenetic factors, especially DNA methylation, have essential roles in obesity development. Here, using pig as a model, we investigate the systematic association between DNA methylation and obesity. We sample eight variant adipose and two distinct skeletal muscle tissues from three pig breeds living within comparable environments but displaying distinct fat level. We generate 1,381 Gb of sequence data from 180 methylated DNA immunoprecipitation libraries, and provide a genome-wide DNA methylation map as well as a gene expression map for adipose and muscle studies. The analysis shows global similarity and difference among breeds, sexes and anatomic locations, and identifies the differentially methylated regions. The differentially methylated regions in promoters are highly associated with obesity development via expression repression of both known obesity-related genes and novel genes. This comprehensive map provides a solid basis for exploring epigenetic mechanisms of adipose deposition and muscle growth