Mesenchymal stem cells (MSCs) serve as an attractive vehicle for cell-directed enzyme prodrug therapy (CDEPT) due to their unique tumour-nesting ability. Such approach holds high therapeutic potential for treating solid tumours including glioblastoma multiforme (GBM), a devastating disease with limited effective treatment options. Currently, it is a common practice in research and clinical manufacturing to use viruses to deliver therapeutic genes into MSCs. However, this is limited by the inherent issues of safety, high cost and demanding manufacturing processes. The aim of this study is to identify a facile, scalable in production and highly efficient non-viral method to transiently engineer MSCs for prolonged and exceptionally high expression of a fused transgene yeast cytosine deaminaseuracil phosphoribosyl-transferasegreen fluorescent protein (CDUPRTGFP).
 
  MSCs were transfected with linear polyethylenimine using a cpg-free plasmid encoding the transgene in the presence of a combination of fusogenic lip this approach was further validated with other well-characterized and clinically annotated patient-derived GBM cells. Additionally, a long-term suppression (> 30 days) of the growth of a subcutaneous TMZ-resistant U-251MG tumour was demonstrated.
 
  Collectively, this highly efficient non-viral workflow could potentially enable the scalable translation of therapeutically engineered MSC for the treatment of TMZ-resistant GBM and other applications beyond the scope of this study.
 Collectively, this highly efficient non-viral workflow could potentially enable the scalable translation of therapeutically engineered MSC for the treatment of TMZ-resistant GBM and other applications beyond the scope of this study.
  Smartphone plays a vital role in higher education as it serves as a device with multiple functions. Smartphone addiction was reported on the rise among college and university students. The addiction may result in unwanted consequences on their academic performance and psychological health. One factor that consistently relates to psychological distress and smartphone addiction is the neurotic personality trait. This study explored the relationship of smartphone addiction with psychological health and neuroticism among USM medical students.
 
  A cross-sectional study was carried out on medical students in a public medical school. DASS-21, the neuroticism-subscale of USMaP-i and SAS-SV were administered to measure psychological distress, neuroticism, and smartphone addiction of the medical students.  https://www.selleckchem.com/products/Gefitinib.html  Spearman correlation was performed to examine the correlation between smartphone addiction with psychological distress and neuroticism. Simple linear regression was performed to investigate relationship factors of sigh prevalence of smartphone addiction among medical students, particularly in male medical students. The smartphone addiction might lead to psychological problems and the most vulnerable group is the medical student with the neurotic personality trait.
 This study suggested a high prevalence of smartphone addiction among medical students, particularly in male medical students. The smartphone addiction might lead to psychological problems and the most vulnerable group is the medical student with the neurotic personality trait.
  Microglia-specific genetic variants are enriched in several neurodegenerative diseases, including Alzheimer's disease (AD), implicating a central role for alterations of the innate immune system in the disease etiology. A rare coding variant in the PLCG2 gene (rs72824905, p.P522R) expressed in myeloid lineage cells was recently identified and shown to reduce the risk for AD.
 
  To assess the role of the protective variant in the context of immune cell functions, we generated a Plcγ2-P522R knock-in (KI) mouse model using CRISPR/Cas9 gene editing.
 
  Functional analyses of macrophages derived from homozygous KI mice and wild type (WT) littermates revealed that the P522R variant potentiates the primary function of Plcγ2 as a Pip2-metabolizing enzyme. This was associated with improved survival and increased acute inflammatory response of the KI macrophages. Enhanced phagocytosis was observed in mouse BV2 microglia-like cells overexpressing human PLCγ2-P522R, but not in PLCγ2-WT expressing cells. Immunohistochemical analyses did not reveal changes in the number or morphology of microglia in the cortex of Plcγ2-P522R KI mice. However, the brain mRNA signature together with microglia-related PET imaging suggested enhanced microglial functions in Plcγ2-P522R KI mice.
 
  The AD-associated protective Plcγ2-P522R variant promotes protective functions associated with TREM2 signaling. Our findings provide further support for the idea that pharmacological modulation of microglia via TREM2-PLCγ2 pathway-dependent stimulation may be a novel therapeutic option for the treatment of AD.
 The AD-associated protective Plcγ2-P522R variant promotes protective functions associated with TREM2 signaling. Our findings provide further support for the idea that pharmacological modulation of microglia via TREM2-PLCγ2 pathway-dependent stimulation may be a novel therapeutic option for the treatment of AD.
  GNE myopathy is an autosomal recessive adult-onset distal myopathy. While a few case reports have described the progression of GNE myopathy during pregnancy, to our knowledge, none have examined disease progression after delivery or obstetric complications.
 
  This study aimed to reveal maternal complications, newborn complications, and the impact of pregnancy on disease progression in GNE myopathy patients.
 
  We conducted a questionnaire survey on pregnancy, delivery, and newborns involving female GNE myopathy patients who are currently registered in a national registry in Japan.
 
  The response rate for the questionnaire survey was 60.0% (72/120). Of the 72 respondents, 44 (61.1%) had pregnancy experience (average, 1.8 pregnancies; 53 pregnancies before onset and 28 after onset). The incidence of threatened abortion was 26.9% among post-onset pregnancies, which was higher compared to those of the general Japanese population (p = 0.03). No other maternal or infant complications were commonly observed. Over 80% were unaware of changes in disease progression during pregnancy (mean age, 32.