Single-cell RNA-seq reveals T cell exhaustion and immune response landscape in osteosarcoma

BackgroundT cell exhaustion in the tumor microenvironment has been demonstrated as a substantial contributor to tumor immunosuppression and progression. However, the correlation between T cell exhaustion and osteosarcoma (OS) remains unclear.MethodsIn our present study, single-cell RNA-seq data for OS from the GEO database was analysed to identify CD8+ T cells and discern CD8+ T cell subsets objectively. Subgroup differentiation trajectory was then used to pinpoint genes altered in response to T cell exhaustion. Subsequently, six machine learning algorithms were applied to develop a prognostic model linked with T cell exhaustion. This model was subsequently validated in the TARGETs and Meta cohorts. Finally, we examined disparities in immune cell infiltration, immune checkpoints, immune-related pathways, and the efficacy of immunotherapy between high and low TEX score groups.ResultsThe findings unveiled differential exhaustion in CD8+ T cells within the OS microenvironment. Three genes related to T cell exhaustion (RAD23A, SAC3D1, PSIP1) were identified and employed to formulate a T cell exhaustion model. This model exhibited robust predictive capabilities for OS prognosis, with patients in the low TEX score group demonstrating a more favorable prognosis, increased immune cell infiltration, and heightened responsiveness to treatment compared to those in the high TEX score group.ConclusionIn summary, our research elucidates the role of T cell exhaustion in the immunotherapy and progression of OS, the prognostic model constructed based on T cell exhaustion-related genes holds promise as a potential method for prognostication in the management and treatment of OS patients

Endothelin-1 single nucleotide polymorphisms and risk of pulmonary metastatic osteosarcoma.

Pulmonary metastases are the major cause of death of osteosarcoma (OS) patients. Endothelin-1 (ET-1) reportedly plays an important role in OS metastasis. In the present study, we for the first time explored the association of ET-1 SNPs with the risk of pulmonary metastatic OS. We genotyped three SNPs (rs1800541, rs2070699 and rs5370) in the ET-1 gene in a case-control study, using 260 pairs of age-, sex-, residence area- and tumor location-matched subjects. Patients with pulmonary metastatic OS and patients with localized high-grade (stage IIB) OS were enrolled as cases and controls, respectively. The G allele at rs1800541 was found associated with reduced risk of pulmonary metastatic OS after adjustment for body mass index, systolic blood pressure, diastolic blood pressure and the plasma ET-1 level (P=10(-4); adjusted OR, 0.55; 95% CI, 0.42-0.70), while the G allele at rs2070699 was not significantly associated with the risk of pulmonary metastatic OS (P=0.15; adjusted OR, 1.15; 95% CI, 0.87-1.50). The mRNA and the secreted protein levels of ET-1 in primary OS cell cultures (POCCs) established from surgically resected primary OS in the rs1800541 TT homozygotes were higher than those from the TG heterozygotes (P<0.05), who in turn showed higher ET-1 mRNA and secreted ET-1 levels than the GG homozygotes (P<0.05). In the control subjects, the rs1800541 TT homozygotes showed an 18.4% relapse rate, significantly higher than that of the GG homozygotes (0%) (P<0.01). On the other hand, the GG homozygotes showed a 71.4% complete recovery rate, significantly higher than that of the TG heterozygotes (7.3%) and the TT homozygotes (0%) (P<0.01). This study provides the first evidence of an association between the ET-1 gene SNPs and the risk of pulmonary metastatic OS

Specific zone within 8-membered ring channel as catalytic center for carbonylation of dimethyl ether and methanol over FER zeolite

The DFT investigation of methanol and dimethyl ether (DME) carbonylation at different sites of FER zeolite is carried out in an attempt to explore whether some specific acid sites are present to selectively catalyze the desired reaction. It is shown that the surface methoxy groups (SMG), generated by the reaction of methanol or DME with the Bronsted acid sites of zeolites, preferentially forms in the 8-membered ring (8MR) and 10-membered ring (10MR) channels. Further study of the CO attack on the SMG shows that, the carbonylation reaction occurs selectively at the 6MR zone of 8MR channel of FER zeolites. This result not only provides a theoretical perspective for the experimentally observed higher carbonylation reactivity of SMG located inside the 8MR channels, but also makes the location of the reaction more accurate

Dual Effects of Cold Storage and Stored Host Eggs of <i>Spodoptera frugiperda</i> (Smith) (Lepidoptera: Noctuidae) on the Reproductive Capacity of <i>Telenomus remus</i> Nixon (Hymenoptera: Scelionidae)

Spodoptera frugiperda is the preferred host of the parasitoid Telenomus remus. Cold storage can preserve a sufficient quantity of parasitoids and their hosts in a laboratory colony for mass release. First, the effects of cold storage on the reproductive capacity of T. remus reared on non-stored S. frugiperda eggs and the hatching rate of unparasitized S. frugiperda eggs were investigated. Further, the dual effects of cold storage and stored S. frugiperda eggs on the reproductive capacity of T. remus were studied to determine the optimal storage conditions and the maximal shelf life for both the host and the parasitoid. The emergence rate, the number of adults produced, and the female proportion of T. remus were affected by cold storage factors. Pupae stored at 13 °C for 15 days is optimum for T. remus reared on non-stored S. frugiperda eggs. Spodoptera frugiperda eggs could only be stored at 10 °C for five days to be suitable for rearing T. remus. The optimum cold storage conditions for T. remus parasitizing stored eggs were 7 °C for 5 days in the larval stage. The maximal shelf lives of T. remus parasitizing cold-stored S. frugiperda eggs were 10 days. Cold storage affected the hatching rate of S. frugiperda eggs, thereby further affecting the reproductive capacity of T. remus. The findings suggest that different storage conditions should be used when mass-rearing T. remus on stored and non-stored eggs. Telenomus remus should be reproduced using fresh laid S. frugiperda eggs for maximum shelf life

A theoretical study on the selective adsorption behavior of dimethyl ether and carbon monoxide on H-FER zeolites

The adsorption behavior of dimethyl ether (DME) and carbon dioxide (CO) on FER zeolite with different Si/AI ratios and Al positions was calculated. For pure CO or DME gas, the CO adsorption quantity rises near linearly with pressure, while the DME adsorption quantity firstly rises rapidly but then rises much moderately at higher pressure. For the CO-DME gas mixture, both CO and DME adsorption quantity rises rapidly but then rises much moderately at higher pressure. Further investigation reveals that CO and DME molecules are preferentially located in the 6-MR zone of the 8-MR channel. (C) 2017 Elsevier B.V. All rights reserved

Relapse Rate and Complete Recovery Rate in Control Subjects by the rs1800541 Polymorphism.

<p>Note: POCC, primary osteosarcoma cell culture. ^a Fisher’s exact <i>P</i> value for GG vs. TT; ^b Fisher’s exact <i>P</i> value for TG vs. TT.</p

Table_1_Regional decreases of cortical thickness in major depressive disorder and their correlation with illness duration: a case-control study.DOCX

BackgroundAlterations in brain structure and function in major depressive disorder (MDD) have been identified in a number of studies, but findings regarding cortical thickness were various and inconsistent. Our current study aims to explore the differences in cortical thickness between individuals with MDD and healthy controls (HC) in a Chinese population.MethodsWe investigated T1-weighted brain magnetic resonance imaging data from 61 participants (31 MDD and 30 HC). The cortical thickness between the two groups and analyzed correlations between cortical thickness and demographic variables in the MDD group for regions with significant between-group differences were conducted.ResultsCompared with the HC group, patients with MDD had significantly decreased cortical thickness, in left pars triangularis, left pars orbitalis, left rostral middle frontal gyrus, left supramarginal gyrus, right parahippocampal gyrus, right lingual gyrus, right fusiform and right inferior parietal gyrus. The cortical thickness of left rostral middle frontal gyrus was negatively correlated (r = −0.47, p = 0.028) with the illness duration in patients with MDD.ConclusionOur study distinguished that cortical thickness decreases in numerous brain regions both in the left and right hemisphere in individuals with MDD, and the negative correlation between the cortical thickness of left rostral middle frontal gyrus illness duration. Our current findings are valuable in providing neural markers to identify MDD and understanding the potential pathophysiology of mood disorders.</p

Image_1_Single-cell RNA-seq reveals T cell exhaustion and immune response landscape in osteosarcoma.jpeg

BackgroundT cell exhaustion in the tumor microenvironment has been demonstrated as a substantial contributor to tumor immunosuppression and progression. However, the correlation between T cell exhaustion and osteosarcoma (OS) remains unclear.MethodsIn our present study, single-cell RNA-seq data for OS from the GEO database was analysed to identify CD8+ T cells and discern CD8+ T cell subsets objectively. Subgroup differentiation trajectory was then used to pinpoint genes altered in response to T cell exhaustion. Subsequently, six machine learning algorithms were applied to develop a prognostic model linked with T cell exhaustion. This model was subsequently validated in the TARGETs and Meta cohorts. Finally, we examined disparities in immune cell infiltration, immune checkpoints, immune-related pathways, and the efficacy of immunotherapy between high and low TEX score groups.ResultsThe findings unveiled differential exhaustion in CD8+ T cells within the OS microenvironment. Three genes related to T cell exhaustion (RAD23A, SAC3D1, PSIP1) were identified and employed to formulate a T cell exhaustion model. This model exhibited robust predictive capabilities for OS prognosis, with patients in the low TEX score group demonstrating a more favorable prognosis, increased immune cell infiltration, and heightened responsiveness to treatment compared to those in the high TEX score group.ConclusionIn summary, our research elucidates the role of T cell exhaustion in the immunotherapy and progression of OS, the prognostic model constructed based on T cell exhaustion-related genes holds promise as a potential method for prognostication in the management and treatment of OS patients.</p