Development of a novel copper metabolism-related risk model to predict prognosis and tumor microenvironment of patients with stomach adenocarcinoma

Background: Stomach adenocarcinoma (STAD) is the fourth highest cause of cancer mortality worldwide. Alterations in copper metabolism are closely linked to cancer genesis and progression. We aim to identify the prognostic value of copper metabolism-related genes (CMRGs) in STAD and the characteristic of the tumor immune microenvironment (TIME) of the CMRG risk model.Methods: CMRGs were investigated in the STAD cohort from The Cancer Genome Atlas (TCGA) database. Then, the hub CMRGs were screened out with LASSO Cox regression, followed by the establishment of a risk model and validated by GSE84437 from the Expression Omnibus (GEO) database. The hub CMRGs were then utilized to create a nomogram. TMB (tumor mutation burden) and immune cell infiltration were investigated. To validate CMRGs in immunotherapy response prediction, immunophenoscore (IPS) and IMvigor210 cohort were employed. Finally, data from single-cell RNA sequencing (scRNA-seq) was utilized to depict the properties of the hub CMRGs.Results: There were 75 differentially expressed CMRGs identified, 6 of which were linked with OS. 5 hub CMRGs were selected by LASSO regression, followed by construction of the CMRG risk model. High-risk patients had a shorter life expectancy than those low-risk. The risk score independently predicted STAD survival through univariate and multivariate Cox regression analyses, with ROC calculation generating the highest results. This risk model was linked to immunocyte infiltration and showed a good prediction performance for STAD patients’ survival. Furthermore, the high-risk group had lower TMB and somatic mutation counters and higher TIDE scores, but the low-risk group had greater IPS-PD-1 and IPS-CTLA4 immunotherapy prediction, indicating a higher immune checkpoint inhibitors (ICIs) response, which was corroborated by the IMvigor210 cohort. Furthermore, those with low and high risk showed differential susceptibility to anticancer drugs. Based on CMRGs, two subclusters were identified. Cluster 2 patients had superior clinical results. Finally, the copper metabolism-related TIME of STAD was concentrated in endothelium, fibroblasts, and macrophages.Conclusion: CMRG is a promising biomarker of prognosis for patients with STAD and can be used as a guide for immunotherapy

A two years longitudinal study of a transgenic Huntington disease monkey

BACKGROUND: A two-year longitudinal study composed of morphometric MRI measures and cognitive behavioral evaluation was performed on a transgenic Huntington’s disease (HD) monkey. rHD1, a transgenic HD monkey expressing exon 1 of the human gene encoding huntingtin (HTT) with 29 CAG repeats regulated by a human polyubiquitin C promoter was used together with four age-matched wild-type control monkeys. This is the first study on a primate model of human HD based on longitudinal clinical measurements. RESULTS: Changes in striatal and hippocampal volumes in rHD1 were observed with progressive impairment in motor functions and cognitive decline, including deficits in learning stimulus-reward associations, recognition memory and spatial memory. The results demonstrate a progressive cognitive decline and morphometric changes in the striatum and hippocampus in a transgenic HD monkey. CONCLUSIONS: This is the first study on a primate model of human HD based on longitudinal clinical measurements. While this study is based a single HD monkey, an ongoing longitudinal study with additional HD monkeys will be important for the confirmation of our findings. A nonhuman primate model of HD could complement other animal models of HD to better understand the pathogenesis of HD and future development of diagnostics and therapeutics through longitudinal assessment

Imaging diagnosis in peripheral nerve injury

Peripheral nerve injuries (PNIs) can be caused by various factors, ranging from penetrating injury to compression, stretch and ischemia, and can result in a range of clinical manifestations. Therapeutic interventions can vary depending on the severity, site, and cause of the injury. Imaging plays a crucial role in the precise orientation and planning of surgical interventions, as well as in monitoring the progression of the injury and evaluating treatment outcomes. PNIs can be categorized based on severity into neurapraxia, axonotmesis, and neurotmesis. While PNIs are more common in upper limbs, the localization of the injured site can be challenging. Currently, a variety of imaging modalities including ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) and positron emission tomography (PET) have been applied in detection and diagnosis of PNIs, and the imaging efficiency and accuracy many vary based on the nature of injuries and severity. This article provides an overview of the causes, severity, and clinical manifestations of PNIs and highlights the role of imaging in their management

Differences in Practitioner Experience, Practice Type, and Profession in Attitudes Toward Growing Contact Lens Practice

OBJECTIVE: To investigate eye care practitioners' attitudes and perceptions toward potential interventions that can enhance contact lens (CL) practice across the world, and how this is influenced by their practice setting. METHODS: A self-administered, anonymized survey was constructed in English and then forward and backward translated into six more languages. The survey was distributed online via social media platforms and mailing lists involving reputed international professional bodies. RESULTS: In total, 2,222 responses from 27 countries with sufficient responses were analyzed (53% females, median age- 37 years). Most of the respondents were optometrists (81.9%) and 47.6% were from stand-alone/independent practices. Median working experience in CL prescribing was 11.0 years (IQR: 18.0, 4-22 years). Over two-third of them declared themselves to be very hopeful (22.9%) or hopeful (45.1%) about the future of their CL practice. Among the potential interventions proposed, continuous update of knowledge and skills and competently managing CL-related complications were rated the most important (median score: 9/10 for each). Practitioners working in national/regional retail chains expressed higher proactivity in recommending CLs (9/10) than those in local chains, hospitals, and universities (for all 8/10, P <0.05). National differences were also identified in eye care practitioner attitudes and perceptions ( P <0.05). CONCLUSIONS: The study provided important information to delineate a variety of elements characterizing CL practice across the world. These insights can serve as a basis to design strategies at national and international levels

A Novel, Portable and Fast Moisture Content Measuring Method for Grains Based on an Ultra-Wideband (UWB) Radar Module and the Mode Matching Method

To perform fast and portable grain moisture measurements under field conditions, a novel moisture sensor was designed, which consisted of a coaxial waveguide, a circular waveguide, and an isolation layer. The electromagnetic characteristics of the sensor were simulated and measured. The analytical model, which represented the relationship between the reflection coefficient of the sensor and the complex permittivity of grain, was established by using the mode matching method. The reflection coefficient of the sensor was measured by using an ultra-wideband (UWB) radar module, and the moisture content of grains was calculated from the complex permittivity by using density-independent model. To verify the performance of the proposed method, wheat, rough rice, and barley were taken as examples. The measured results in the range from 1.0% to 26.0%, wet basis, agreed well with the reference values (R2 was more than 0.99), and the maximum absolute errors for wheat, rough rice, and barley were 1.1%, 1.0%, and 1.4%, respectively. In addition, the effect of isolation layer was discussed. Both the simulation results and the experimental results showed that the isolation layer improved the stability of sensor

Gremlin induces cell proliferation and extra cellular matrix accumulation in mouse mesangial cells exposed to high glucose via the ERK1/2 pathway

Abstract Background Gremlin, a bone morphogenetic protein antagonist, plays an important role in the pathogenesis of diabetic nephropathy (DN). However, the specific molecular mechanism underlying Gremlin’s involvement in DN has not been fully elucidated. In the present study, we investigated the role of Gremlin on cell proliferation and accumulation of extracellular matrix (ECM) in mouse mesangial cells (MMCs), and explored the relationship between Gremlin and the ERK1/2 pathway. Methods To determine expression of Gremlin in MMCs after high glucose (HG) exposure, Gremlin mRNA and protein expression were evaluated using real-time polymerase chain reaction and western blot analysis, respectively. To determine the role of Gremlin on cell proliferation and accumulation of ECM, western blot analysis was used to assess expression of pERK1/2, transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF). Cell proliferation was examined by bromodeoxyuridine (BrdU) ELISA, and accumulation of collagen IV was measured using a radioimmunoassay. This enabled the relationship between Gremlin and ERK1/2 pathway activation to be investigated. Results HG exposure induced expression of Gremlin, which peaked 12 h after HG exposure. HG exposure alone or transfection of normal-glucose (NG) exposed MMCs with Gremlin plasmid (NG + P) increased cell proliferation. Transfection with Gremlin plasmid into MMCs previously exposed to HG (HG + P) significantly increased this HG-induced phenomenon. HG and NG + P conditions up-regulated protein levels of TGF-β1, CTGF and collagen IV accumulation, while HG + P significantly increased levels of these further. Inhibition of Gremlin with Gremlin siRNA plasmid reversed the HG-induced phenomena. These data indicate that Gremlin can induce cell proliferation and accumulation of ECM in MMCs. HG also induced the activation of the ERK1/2 pathway, which peaked 24 h after HG exposure. HG and NG + P conditions induced overexpression of pERK1/2, whilst HG + P significantly induced levels further. Inhibition of Gremlin by Gremlin siRNA plasmid reversed the HG-induced phenomena. This indicates Gremlin can induce activation of the ERK1/2 pathway in MMCs. Conclusion Culture of MMCs in the presence of HG up-regulates expression of Gremlin. Gremlin induces cell proliferation and accumulation of ECM in MMCs. and enhances activation of the ERK1/2 pathway.</p