Mu opioid receptor mRNA overexpression predicts poor prognosis among 18 common solid cancers: A pan-cancer analysis

BackgroundOpioids are widely used for patients with solid tumors during surgery and for cancer pain relief. We conducted a pan-cancer genomic analysis to investigate the prognostic features of Mu opioid receptor (MOR) mRNA expression across 18 primary solid cancers.MethodsAll the data of cancer with MOR mRNA were retrieved from cBioPortal for Cancer Genomics. Logistic regression was used to determine the associations between MOR mRNA expression and clinicopathological features. Log-rank test and Cox regression was used for survival analysis. Subgroup analysis and propensity score matching were also carried out.Results7,274 patients, including 1,112 patients with positive MOR mRNA expression, were included for data analyses. Positive MOR mRNA expression was associated with more advanced stage of T (adjusted Odds ratio [OR], 1.176; 95% confidence interval [CI], 1.022-1.354; P=0.024), M (adjusted OR, 1.548; 95% CI, 1.095-2.189; P=0.013) except N (adjusted OR, 1.145; 95% CI, 0.975-1.346; P=0.101), and worse prognosis for overall survival (Hazard ratio [HR] 1.347, 95% CI 1.200-1.512, P<0.001), progression-free survival (HR 1.359, 95% CI 1.220-1.513, P<0.001), disease-free survival (HR 1.269, 95% CI 1.016-1.585, P<0.001) and disease-specific survival (HR 1.474, 95% CI 1.284-1.693, P<0.001). Patients with positive MOR mRNA expression tended to be classified as tumor microenvironment immune types II, representing low PD-L1 and low CD8A expression.ConclusionMOR mRNA overexpression is associated with poor prognosis and poor response to PD-L1 therapy

A critical assessment of Mus musculus gene function prediction using integrated genomic evidence

Background: Several years after sequencing the human genome and the mouse genome, much remains to be discovered about the functions of most human and mouse genes. Computational prediction of gene function promises to help focus limited experimental resources on the most likely hypotheses. Several algorithms using diverse genomic data have been applied to this task in model organisms; however, the performance of such approaches in mammals has not yet been evaluated. Results: In this study, a standardized collection of mouse functional genomic data was assembled; nine bioinformatics teams used this data set to independently train classifiers and generate predictions of function, as defined by Gene Ontology (GO) terms, for 21,603 mouse genes; and the best performing submissions were combined in a single set of predictions. We identified strengths and weaknesses of current functional genomic data sets and compared the performance of function prediction algorithms. This analysis inferred functions for 76% of mouse genes, including 5,000 currently uncharacterized genes. At a recall rate of 20%, a unified set of predictions averaged 41% precision, with 26% of GO terms achieving a precision better than 90%. Conclusion: We performed a systematic evaluation of diverse, independently developed computational approaches for predicting gene function from heterogeneous data sources in mammals. The results show that currently available data for mammals allows predictions with both breadth and accuracy. Importantly, many highly novel predictions emerge for the 38% of mouse genes that remain uncharacterized

Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion

The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban

Meroterpenoids from Ganoderma Species: A Review of Last Five Years

Abstract Meroterpenoids are hybrid natural products that partially originate from the terpenoid pathway. Ganoderma meroterpenoids (GMs) are a type of meroterpenoids containing a 1,2,4-trisubstituted phenyl and a polyunsaturated terpenoid part. Over last 5 years, great efforts have been made to conduct phytochemistry research on the genus Ganoderma, which have led to the isolation and identification of a number of GMs. These newly reported GMs showed diverse structures and a wide range of biological activities. This review gives an overview of new GMs from genus Ganoderma and their biological activities and biosynthetic pathway, focusing on the period from 2013 until 2018. Graphical Abstrac

Machine learning-assisted structure annotation of natural products based on MS and NMR data

Machine learning (ML) has emerged as a popular tool for analyzing the structures of natural products (NPs). This review presents a summary of the recent advancements in ML-assisted mass spectrometry (MS) and nuclear magnetic resonance (NMR) data analysis to establish the chemical structures of NPs. First, ML-based MS/MS analyses that rely on library matching are discussed, which involves the utilization of ML algorithms to calculate similarity, predict the MS/MS fragments, and form molecular fingerprint. Then, ML assisted MS/MS structural annotation without library matching is reviewed. Furthermore, the cases of ML algorithms in assisting structural studies of NPs based on NMR are discussed from four perspectives: NMR prediction, functional group identification, structural categorization and quantum chemical calculation. Finally, the review concludes with a discussion of the challenges and the trends associated with the structural establishment of NPs based on ML algorithms

High Level of Ammonium Nitrogen Increases Net Ecosystem Productivity in a <i>Quercus liaotungensis</i> Forest in Northern China

Forest ecosystems are vital to the terrestrial ecosystem’s carbon (C) cycle. The effects of nitrogen (N) addition on C sequestration in forest ecosystems are critical for better understanding C dynamics when facing an increase in N availability. We conducted a six-year field experiment to examine the effects of N addition on C sequestration and net ecosystem productivity (NEP) in a Quercus liaotungensis forest in northern China. N addition resulted in a significant increase in biomass C storage (17.54–48.62%) and changed the distribution patterns of above and belowground biomass C storage, resulting in a 9.64 to 23.23% reduction in the proportion of belowground biomass C compared with the control. The annual average heterotrophic respiration was significantly increased by the additional N (by 0.06–0.94 Mg C ha−1 yr1). In comparison with the control, the C sequestration efficiency driven by N addition ranged from 7.12 to 33.50 kg C/kg N. High-level N addition exerted stronger effects on ecosystem C sequestration than low-level N addition. NH4+-N, rather than NO3−-N, dominated the increase in ecosystem C sequestration. We found that Q. liaotungensis forest acted as a C sink. The increase in NEP in the study forest in northern China was mainly due to an increase in net primary productivity (NPP) caused by N addition. Atmospheric N deposition increased the C sequestration efficiency depending on the rate and form of N deposition