Transmembrane and coiled-coil domains 3 is a diagnostic biomarker for predicting immune checkpoint blockade efficacy in hepatocellular carcinoma

Liver hepatocellular carcinoma (LIHC) is a malignancy with a high mortality and morbidity rate worldwide. However, the pathogenesis of LIHC has still not been thoroughly studied. Transmembrane and coiled-coil domains 3 (TMCO3) encodes a monovalent cation, a member of the proton transducer 2 (CPA2) family of transporter proteins. In the present study, TMCO3 expression and its relationship with cancer prognosis, as well as its immunological role in LIHC were studied by bioinformatic analysis. We found the significant overexpression of TMCO3 in LIHC in the TCGA, HCCDB, and GEO databases. In LIHC patients, high TMCO3 expression was related to poorer overall survival (OS) and TMCO3 had good predictive accuracy for prognosis. Moreover, TMCO3 was linked to the infiltrates of certain immune cells in LIHC. The correlation of TMCO3 with immune checkpoints was also revealed. Moreover, patients with LIHC with low TMCO3 expression showed a better response to immune checkpoint blockade (ICB) than those with LIHC with high TMCO3 expression. GO and KEGG enrichment analyses indicated that TMCO3 was probably involved in the microtubule cytoskeleton organization involved in mitosis, small GTPase mediated signal transduction, and TGF-β pathway. In conclusion, TMCO3 may be a potential biomarker for LIHC prognosis and immunotherapy

Emergence of central recirculation zone in a V-shaped premixed swirling flame

This paper presents an experimental study on the emergence of the central recirculation zone (CRZ) in a V-shaped premixed swirling flame, using simultaneous measurement of particle image velocimetry (PIV) and CH* chemiluminescence. The results show that either increasing the Reynolds number (Re) or decreasing the equivalence ratio ({\phi}) would facilitate the emergence of CRZ, and the inner shear layer (ISL) plays an essential role in governing the characteristics of CRZ. Further analysis demonstrates that the CRZ emergence can be promoted by higher ISL intensity but suppressed by enhanced viscous diffusion owing to higher flame temperature. As such, the CRZ formation can be interpreted as the outcome of a competition between the ISL intensity, i.e., circulation, and the vorticity consumption due to viscous diffusion. This competition physically corresponds to a special Reynolds number, Re_s, defined as the ratio between the ISL circulation ({\Gamma}) and the ISL effective viscosity ({\nu}_s), with a simplified heat loss model proposed for the temperature and viscosity estimations of the ISL. The outputting {\Gamma}-{\nu}_s plot yields a single boundary line separating the cases with and without CRZ, which points to a common critical Re_s of about 637, justifying the generality of the present criterion for lean-premixed V-shaped swirling flames of various operating conditions. Unlike most previous works which study the CRZ of a swirling flame from the point of vortex breakdown, the present work reveals the importance of enhanced viscous diffusion, caused by flame heating, in suppressing the CRZ emergence

Predictive value of PIMREG in the prognosis and response to immune checkpoint blockade of glioma patients

Glioma is the most common primary brain tumor in the human brain. The present study was designed to explore the expression of PIMREG in glioma and its relevance to the clinicopathological features and prognosis of glioma patients. The correlations of PIMREG with the infiltrating levels of immune cells and its relevance to the response to immunotherapy were also investigated. PIMREG expression in glioma was analyzed based on the GEO, TCGA, and HPA databases. Kaplan–Meier survival analysis was used to examine the predictive value of PIMREG for the prognosis of patients with glioma. The correlation between the infiltrating levels of immune cells in glioma and PIMREG was analyzed using the CIBERSORT algorithm and TIMRE database. The correlation between PIMREG and immune checkpoints and its correlation with the patients’ responses to immunotherapy were analyzed using R software and the GEPIA dataset. Cell experiments were conducted to verify the action of PIMREG in glioma cell migration and invasion. We found that PIMREG expression was upregulated in gliomas and positively associated with WHO grade. High PIMREG expression was correlated with poor prognosis of LGG, prognosis of all WHO grade gliomas, and prognosis of recurrent gliomas. PIMREG was related to the infiltration of several immune cell types, such as M1 and M2 macrophages, monocytes and CD8+ T cells. Moreover, PIMREG was correlated with immune checkpoints in glioma and correlated with patients’ responses to immunotherapy. KEGG pathway enrichment and GO functional analysis illustrated that PIMREG was related to multiple tumor- and immune-related pathways. In conclusion, PIMREG overexpression in gliomas is associated with poor prognosis of patients with glioma and is related to immune cell infiltrates and the responses to immunotherapy

Fully Band Resolved Scattering Rate in MgB2 Revealed by Nonlinear Hall Effect and Magnetoresistance Measurements

We have measured the normal state temperature dependence of the Hall effect and magnetoresistance in epitaxial MgB2 thin films with variable disorders characterized by the residual resistance ratio RRR ranging from 4.0 to 33.3. A strong nonlinearity of the Hall effect and magnetoresistance have been found in clean samples, and they decrease gradually with the increase of disorders or temperature. By fitting the data to the theoretical model based on the Boltzmann equation and ab initio calculations for a four-band system, for the first time, we derived the scattering rates of these four bands at different temperatures and magnitude of disorders. Our method provides a unique way to derive these important parameters in multiband systems.Comment: 4 pages, 4 figure

A Phase 1 Study of ADI-PEG20 (Pegargiminase) Combined with Cisplatin and Pemetrexed in ASS1-Negative Metastatic Uveal Melanoma

Metastatic uveal melanoma (UM) is a devastating disease with few treatment options. We evaluated the safety, tolerability and preliminary activity of arginine depletion using pegylated arginine deiminase (ADI-PEG20; pegargiminase) combined with pemetrexed (Pem) and cisplatin (Cis) chemotherapy in a phase 1 dose-expansion study of patients with argininosuccinate synthetase (ASS1)-deficient metastatic UM. Eligible patients received up to six cycles of Pem (500 mg/m2 ) and Cis (75 mg/m2 ) every three weeks plus weekly intramuscular ADI (36 mg/m2 ), followed by maintenance ADI until progression (NCT02029690). Ten of fourteen ASS1-deficient patients with UM liver metastases and a median of one line of prior immunotherapy received ADIPemCis. Only one ≥ grade 3 adverse event of febrile neutropenia was reported. Seven patients had stable disease with a median progression-free survival of 3.0 months (range, 1.3-8.1) and a median overall survival of 11.5 months (range, 3.2-36.9). Despite anti-ADI-PEG20 antibody emergence, plasma arginine concentrations remained suppressed by 18 weeks with a reciprocal increase in plasma citrulline. Tumour rebiopsies at progression revealed ASS1 re-expression as an escape mechanism. ADIPemCis was well tolerated with modest disease stabilisation in metastatic UM. Further investigation of arginine deprivation is indicated in UM including combinations with immune checkpoint blockade and additional antimetabolite strategies

Aldehyde Dehydrogenase-2 Attenuates Myocardial Remodeling and Contractile Dysfunction Induced by a High-Fat Diet

Background/Aims: Consumption of a high-fat (HF) diet exacerbates metabolic cardiomyopathy through lipotoxic mechanisms. In this study, we explored the role of aldehyde dehydrogenase-2 (ALDH2) in myocardial damage induced by a HF diet. Methods: Wild-type C57 BL/6J mice were fed a HF diet or control diet for 16 weeks. ALDH2 overexpression was achieved by injecting a lentiviral ALDH2 expression vector into the left ventricle. Results: Consumption of a HF diet induced metabolic syndrome and myocardial remodeling, and these deleterious effects were attenuated by ALDH2 overexpression. In addition, ALDH2 overexpression attenuated the cellular apoptosis and insulin resistance associated with a HF diet. Mechanistically, ALDH2 overexpression inhibited the expression of c-Jun N-terminal kinase (JNK)-1, activated protein 1 (AP-1), insulin receptor substrate 1 (IRS-1), 4- hydroxynonenal, caspase 3, transforming growth factor β1, and collagen I and III, and enhanced Akt phosphorylation. Conclusion: ALDH2 may effectively attenuate myocardial remodeling and contractile defects induced by a HF diet through the regulation of the JNK/AP-1 and IRS-1/Akt signaling pathways. Our study demonstrates that ALDH2 plays an essential role in protecting cardiac function from lipotoxic cardiomyopathy

Manometric Measurement of the Sphincter of Oddi in Patients with Common Bile Duct Stones: A Consecutive Study of the Han Population of China

Objective. Role of dysfunction of the sphincter of Oddi (SO) in choledocholithiasis is controversial. This study was to evaluate SO motor activity in patients with common bile duct (CBD) stones in the Han population of China. Patients and Methods. In this study, 76 patients with CBD stones were enrolled in a single tertiary endoscopy center. Data of SO motor activities was prospectively evaluated by endoscopic manometry. Mean basal SO pressure, amplitude, and frequency were collected and analyzed. Results. The mean basal SO pressure, amplitude, and frequency were 52.7±40.0 (1.60–171.1) mmHg, 39.9±19.7 (14.9–115.5) mmHg, and 5.7±3.2 (1.3–13.8)/min, respectively. The basal SO pressure was higher in patients with CBD stones < 10 mm in diameter than that in those with CBD stones larger than 10 mm in diameter (60.7±41.0 mmHg versus 36.8±29.4 mmHg, P=0.043). There was no significant difference in the basal SO pressure, amplitude, and frequency when compared with the CBD diameter, CBD stone number, prior cholecystectomy, periampullary diverticula, and symptoms. Levels of alanine aminotransferase, aspartate transaminase, γ-glutamyl transpeptidase, and alkaline phosphatase showed no significant difference in patients with normal or elevated basal SO pressure. Conclusion. These results identify that, in Chinese Han population, abnormalities of SO motor activity are associated with CBD stones