Magnetic resonance imaging and deoxyribonucleic acid methylation-based radiogenomic models for survival risk stratification of glioblastoma.

Glioblastoma multiforme (GBM) is one of the deadliest tumours. This study aimed to construct radiogenomic prognostic models of glioblastoma overall survival (OS) based on magnetic resonance imaging (MRI) Gd-T1WI images and deoxyribonucleic acid (DNA) methylation-seq and to understand the related biological pathways. The ResNet3D-18 model was used to extract radiomic features, and Lasso-Cox regression analysis was utilized to establish the prognostic models. A nomogram was constructed by combining the radiogenomic features and clinicopathological variables. The DeLong test was performed to compare the area under the curve (AUC) of the models. We screened differentially expressed genes (DEGs) with original ribonucleic acid (RNA)-seq in risk stratification and used Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) annotations for functional enrichment analysis. For the 1-year OS models, the AUCs of the radiogenomic set, methylation set and deep learning set in the training cohort were 0.864, 0.804 and 0.787, and those in the validation cohort were 0.835, 0.768 and 0.651, respectively. The AUCs of the 0.5-, 1- and 2-year nomograms in the training cohort were 0.943, 0.861 and 0.871, and those in the validation cohort were 0.864, 0.885 and 0.805, respectively. A total of 245 DEGs were screened; functional enrichment analysis showed that these DEGs were associated with cell immunity. The survival risk-stratifying radiogenomic models for glioblastoma OS had high predictability and were associated with biological pathways related to cell immunity.

System analysis based on the migration- and invasion-related gene sets identifies the infiltration-related genes of glioma.

The current database has no information on the infiltration of glioma samples. Here, we assessed the glioma samples' infiltration in The Cancer Gene Atlas (TCGA) through the single-sample Gene Set Enrichment Analysis (ssGSEA) with migration and invasion gene sets. The Weighted Gene Co-expression Network Analysis (WGCNA) and the differentially expressed genes (DEGs) were used to identify the genes most associated with infiltration. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the major biological processes and pathways. Protein-protein interaction (PPI) network analysis and the least absolute shrinkage and selection operator (LASSO) were used to screen the key genes. Furthermore, the nomograms and receiver operating characteristic (ROC) curve were used to evaluate the prognostic and predictive accuracy of this clinical model in patients in TCGA and the Chinese Glioma Genome Atlas (CGGA). The results showed that turquoise was selected as the hub module, and with the intersection of DEGs, we screened 104 common genes. Through LASSO regression, TIMP1, EMP3, IGFBP2, and the other nine genes were screened mostly in correlation with infiltration and prognosis. EMP3 was selected to be verified in vitro. These findings could help researchers better understand the infiltration of gliomas and provide novel therapeutic targets for the treatment of gliomas.

Gut Microbiota and Metabolome Changes in Three Pulmonary Hypertension Rat Models.

Dysbiosis of the gut microbiota and metabolites is found in both pulmonary hypertension patients and pulmonary hypertension rodent models. However, the exact changes in gut microbiota during the development of pulmonary hypertension is unclear. The function of the gut microbiota is also ambiguous. Here, this study showed that the gut microbiota was disrupted in rats with hypoxia (Hyp)-, hypoxia/Sugen5416 (HySu)-, and monocrotaline (MCT)-induced pulmonary hypertension. The gut microbiota is dynamically changed during the development of Hyp-, HySu-, and MCT-induced rat pulmonary hypertension. The variation in the α diversity of the gut microbiota in Hyp-induced pulmonary hypertension rats was similar to that in rats with MCT-induced pulmonary hypertension and different from that in rats with HySu-induced pulmonary hypertension. In addition, six plasma biomarkers, His, Ala, Ser, ADMA, 2-hydroxybutyric acid, and cystathionine, were identified in Hyp-induced pulmonary hypertension rats. Furthermore, a disease-associated network connecting Streptococcus with Hyp-induced pulmonary hypertension-associated metabolites was described here, including trimethylamine N-oxide, Asp, Asn, Lys, His, Ser, Pro, and Ile.

Marine environmental monitoring with unmanned vehicle platforms: Present applications and future prospects.

Basic monitoring of the marine environment is crucial for the early warning and assessment of marine hydrometeorological conditions, climate change, and ecosystem disasters. In recent years, many marine environmental monitoring platforms have been established, such as offshore platforms, ships, or sensors placed on specially designed buoys or submerged marine structures. These platforms typically use a variety of sensors to provide high-quality observations, while they are limited by low spatial resolution and high cost during data acquisition. Satellite remote sensing allows monitoring over a larger ocean area; however, it is susceptible to cloud contamination and atmospheric effects that subject the results to large uncertainties. Unmanned vehicles have become more widely used as platforms in marine science and ocean engineering in recent years due to their ease of deployment, mobility, and the low cost involved in data acquisition. Researchers can acquire data according to their schedules and convenience, offering significant improvements over those obtained by traditional platforms. This study presents the state-of-the-art research on available unmanned vehicle observation platforms, including unmanned aerial vehicles (UAVs), underwater gliders (UGs), unmanned surface vehicles (USVs), and unmanned ships (USs), for marine environmental monitoring, and compares them with satellite remote sensing. The recent applications in marine environments have focused on marine biochemical and ecosystem features, marine physical features, marine pollution, and marine aerosols monitoring, and their integration with other products are also analysed. Additionally, the prospects of future ocean observation systems combining unmanned vehicle platforms (UVPs), global and regional autonomous platform networks, and remote sensing data are discussed.

In-hospital mortality and SpO2 incritical care patients with cerebral injury: data from the MIMIC­IV Database.

BACKGROUND: Evidence regarding the relationship between in-hospital mortality and SpO2 was low oxygen saturations are often thought to be harmful, new research in patients with brain damage has found that high oxygen saturation actually enhances mortality. However, there is currently no clear study to point out the appropriate range for oxygen saturation in patients with craniocerebral diseases.  METHODS: By screening all patients in the MIMIC IV database, 3823 patients with craniocerebral diseases (according to ICD-9 codes and ICD-10) were selected, and non-linear regression was used to analyze the relationship between in-hospital mortality and oxygen saturation. Covariates for all patients included age, weight, diagnosis, duration of ICU stay, duration of oxygen therapy, etc. RESULTS: In-hospital mortality in patients with TBI and SAH was kept to a minimum when oxygen saturation was in the 94-96 range. And in all patients, the relationship between oxygen saturation and in-hospital mortality was U-shaped. Subgroup analysis of the relationship between oxygen saturation and mortality in patients with metabolic encephalopathy and other encephalopathy also draws similar conclusions In-hospital mortality and oxygen saturation were all U-shaped in patients with subarachnoid hemorrhage, metabolic and toxic encephalopathy, cerebral infarction, and other encephalopathy, but the nonlinear regression was statistically significant only in patients with cerebral infarction (p for nonlinearity = 0.002). CONCLUSION: Focusing too much on the lower limit of oxygen saturation and ignoring too high oxygen saturation can also lead to increase in-hospital mortality. For patients with TBI and SAH, maintaining oxygen saturation at 94-96% will minimize the in-hospital mortality of patients.

Serum hsa-circ-0025244 as a biomarker in Chinese occupational mercury-exposed population and mediate apoptosis through JNK/p38 MAPK signaling pathway.

BACKGROUND: circRNAs have been recognized as biomarkers of numerous diseases. We would like to explore the expression pattern and molecular mechanisms of circRNAs in the Chinese occupational mercury-exposed population. METHODS: The workers from a thermometer manufacturing plant and lamp factory in Jiangsu province of China were recruited in 2016. Blood samples were collected from the subjects with chronic mercury poisoning group, mercury absorption group, and the healthy controls. The differentially expressed circRNAs (DECRs) between the three groups were screened from serum samples using a circRNA microarray. The significant DECRs were validated by qRT-PCR, and their respective diagnostic values for mercury poisoning and mercury absorption were analyzed by receiver operating characteristic (ROC) curves. For in vitro experiments, 293T cells were treated with different doses of HgCl2 to determine the half-lethal concentration. The cells were transfected with the siRNA construct or expression plasmid of circRNA. The expression levels of JNK, p38, and caspase family proteins were analyzed by Western blotting. RESULTS: hsa_circ_0025244 was up-regulated in the mercury poisoning and absorption groups compared to the control group (P < 0.05), and positively correlated with the urine mercury levels (P < 0.05). The area under the ROC curve (AUC) of hsa_circ_0025244 for diagnosing occupational mercury poisoning was 0.748, indicating moderate accuracy (P < 0.001). Moreover, the diagnostic accuracy of occupational mercury absorption was high (P < 0.001) with an AUC of 0.918. Knockdown of hsa_circ_0025244 in 293T cells significantly reduced the expression levels of JNK/p38, and caspase family proteins compared to that in the control cells (P < 0.01), and its overexpression led to opposite effects (P < 0.05). CONCLUSIONS: hsa_circ_0025244 is a potential biomarker for mercury exposure and mediates mercury-induced apoptosis in 293T cells by activating the JNK/p38 MAPK signaling pathway.

Coherent Fourier scatterometry nanoparticle detection enhanced by synthetic optical holography.

We demonstrate that the sensitivity of nanoparticle detection on surfaces can be substantially improved by implementing synthetic optical holography (SOH) in coherent Fourier scatterometry (CFS), resulting in a phase-sensitive confocal differential detection technique that operates at very low power level (P = 0.016 mW). The improvement in sensitivity is due to two reasons: first, the boost in the signal at the detector due to the added reference beam; and second, the reduction of background noise caused by the electronics. With this new system, we are able to detect a 60-nm polystyrene latex (PSL) particle at a wavelength of 633 nm (∼λ/10) on a silicon wafer with an improvement in the signal-to-noise ratio (SNR) of approximately 4 dB.

Methylation-mediated silencing of PTPRD induces pulmonary hypertension by promoting pulmonary arterial smooth muscle cell migration via the PDGFRB/PLCγ1 axis.

OBJECTIVE: Pulmonary hypertension is a lethal disease characterized by pulmonary vascular remodeling and is mediated by abnormal proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). Platelet-derived growth factor BB (PDGF-BB) is the most potent mitogen for PASMCs and is involved in vascular remodeling in pulmonary hypertension development. Therefore, the objective of our study is to identify novel mechanisms underlying vascular remodeling in pulmonary hypertension. METHODS: We explored the effects and mechanisms of PTPRD downregulation in PASMCs and PTPRD knockdown rats in pulmonary hypertension induced by hypoxia. RESULTS: We demonstrated that PTPRD is dramatically downregulated in PDGF-BB-treated PASMCs, pulmonary arteries from pulmonary hypertension rats, and blood and pulmonary arteries from lung specimens of patients with hypoxic pulmonary arterial hypertension (HPAH) and idiopathic PAH (iPAH). Subsequently, we found that PTPRD was downregulated by promoter methylation via DNMT1. Moreover, we found that PTPRD knockdown altered cell morphology and migration in PASMCs via modulating focal adhesion and cell cytoskeleton. We have demonstrated that the increase in cell migration is mediated by the PDGFRB/PLCγ1 pathway. Furthermore, under hypoxic condition, we observed significant pulmonary arterial remodeling and exacerbation of pulmonary hypertension in heterozygous PTPRD knock-out rats compared with the wild-type group. We also demonstrated that HET group treated with chronic hypoxia have higher expression and activity of PLCγ1 in the pulmonary arteries compared with wild-type group. CONCLUSION: We propose that PTPRD likely plays an important role in the process of pulmonary vascular remodeling and development of pulmonary hypertension in vivo .

MicroRNAs in Pulmonary Hypertension, from Pathogenesis to Diagnosis and Treatment.

Pulmonary hypertension (PH) is a fatal and untreatable disease, ultimately leading to right heart failure and eventually death. microRNAs are small, non-coding endogenous RNA molecules that can regulate gene expression and influence various biological processes. Changes in microRNA expression levels contribute to various cardiovascular disorders, and microRNAs have been shown to play a critical role in PH pathogenesis. In recent years, numerous studies have explored the role of microRNAs in PH, focusing on the expression profiles of microRNAs and their signaling pathways in pulmonary artery smooth muscle cells (PASMCs) or pulmonary artery endothelial cells (PAECs), PH models, and PH patients. Moreover, certain microRNAs, such as miR-150 and miR-26a, have been identified as good candidates of diagnosis biomarkers for PH. However, there are still several challenges for microRNAs as biomarkers, including difficulty in normalization, specificity in PH, and a lack of longitudinal and big sample-sized studies. Furthermore, microRNA target drugs are potential therapeutic agents for PH treatment, which have been demonstrated in PH models and in humans. Nonetheless, synthetic microRNA mimics or antagonists are susceptible to several common defects, such as low drug efficacy, inefficient drug delivery, potential toxicity and especially, off-target effects. Therefore, finding clinically safe and effective microRNA drugs remains a great challenge, and further breakthrough is urgently needed.

Salt-Inducible Kinase 3 Haplotypes Associated with Noise-Induced Hearing Loss in Chinese Workers.

INTRODUCTION: Noise-induced hearing loss (NIHL) is a common occupational disease that represents an irreversible hearing damage to the auditory system. It has been identified as a complicated disease involving both environmental and genetic factors. More efforts need to be made to explore the genes associated with susceptibility to NIHL. The main aim of this research is to detect the associations between SIK3 polymorphisms and NIHL susceptibility in Han people in China. METHODS: A case-control study was performed in 586 cases and 639 controls in a textile factory matched for sex, age, smoking, drinking, work time with noise, and intensity of noise exposure. Three single nucleotide polymorphisms (SNPs) (rs493134, rs6589574, and rs7121898) of SIK3 were genotyped in the participants. Then, the main influences of the SNPs on and their interactions with NIHL were assessed. RESULTS: Under the allelic model, distributions of rs493134 T, rs6589574 G, and rs7121898 A in the NIHL group are statistically different from those of the normal group (p = 0.001, p < 0.001, and p = 0.019, respectively). The following haplotype analysis shows that TAA (rs493134-rs6589574-rs7121898) may have a protective effect, while TGA (rs493134-rs6589574-rs7121898) (OR = 1.49, 95% CI = 1.25-1.79) may be a risk factor for NIHL. Multifactor dimensionality reduction analysis shows that the interaction of the 3 selected SNPs is associated with NIHL susceptibility (OR = 1.88, 95% CI = 1.50-2.36). CONCLUSION: The results suggest that 3 SNPs (rs493134, rs6589574, and rs7121898) of SIK3 may be an important part of NIHL susceptibility and can be applied in the prevention, early diagnosis, and treatment of NIHL in noise-exposed Chinese workers.

Research and Discussion on the Relationships between Noise-Induced Hearing Loss and ATP2B2 Gene Polymorphism.

Long-term and continuous noise exposure can result in noise-induced hearing loss (NIHL), which is a worldwide problem resulting from the interaction of environmental and genetic factors. The ATP2B2 gene polymorphism can destroy cochlear hair cells and increase the risk of NIHL. A case-control study of 760 Chinese textile workers was conducted to investigate the relationship between ATP2B2 polymorphisms and NIHL susceptibility. Venous blood was collected and questionnaires were conducted by professional physicians. A case group and a control group which were typed by individuals' pure-tone audiometry test results were set. Three polymorphism sites of ATP2B2 were genotyped by using the PCR technique. Analysis results revealed that the C allele of rs3209637 (95%CI = 1.08-2.58, odds ratio (OR) = 1.67, P = 0.027) was a dangerous factor and could add to risks of NIHL in the Chinese employees. The data of stratified analysis revealed that individuals who are exposed to noise > 95 dB with the rs3209637 C genotype have a higher susceptibility to NIHL (OR = 1.34, 95%CI = 1.07-1.68). Multifactor dimensionality reduction analysis revealed that the interaction between rs14154 and rs3209637 is linked to increased NIHL risk, and for the interaction among rs14154, smoking and drinking had the same function (OR = 1.54 and 1.77, 95%CI = 1.15-2.07, 1.33-2.37, and P = 0.0037 and P < 0.0001, respectively). Our results suggest that genetic polymorphism rs3209637 C within ATP2B2 is a risk factor for NIHL among Chinese employees and rs3209637 C could be a potential biomarker for NIHL patients.

LHX3 is an advanced-stage prognostic biomarker and metastatic oncogene in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer and exhibits high morbidity and mortality in the world. We recently identified LHX3 as a preferentially expressed gene with a possible involvement in HCC. OBJECTIVE: To determine the expression, clinical relevance, prognostic significance and functions of LHX3 in HCC. MATERIALS AND METHODS: LHX3 expression was assessed in 190 cancerous and 40 adjacent non-cancerous tissues by PCR, western blot and immunohistochemistry. Associations between LHX3 expression and clinicopathological characteristics of patients were investigated. Correlations between LHX3 expression and overall survival of patients were analyzed by Kaplan-Meier and Cox-regression methods. Functional roles of LHX3 were evaluated by transwell assays. RESULTS: LHX3 expression is significantly increased in carcinoma tissues, and associated with clinical stage and metastasis of patients. LHX3 expression is much higher in the advanced-stage patients than the early-stage patients, and is sharply increased in metastasic patients. High LHX3 expression is associated with unfavorable overall survival, and is an independent prognostic factor of patients. Moreover, LHX3 is an unfavorable and independent prognostic factor unique to advanced-stage patients. Knockdown expression of LHX3 obviously inhibits tumor cell migration and invasion. CONCLUSION: LHX3 is an advanced-stage prognostic biomarker, and acts as a new potential metastatic oncogene in HCC.