SlRBP1 promotes translational efficiency via SleIF4A2 to maintain chloroplast function in tomato.

Many glycine-rich RNA-binding proteins (GR-RBPs) have critical functions in RNA processing and metabolism. Here, we describe a role for the tomato (Solanum lycopersicum) GR-RBP SlRBP1 in regulating mRNA translation. We found that SlRBP1 knockdown mutants (slrbp1) displayed reduced accumulation of total chlorophyll and impaired chloroplast ultrastructure. These phenotypes were accompanied by deregulation of the levels of numerous key transcripts associated with chloroplast functions in slrbp1. Furthermore, native RNA immunoprecipitation-sequencing (nRIP-seq) recovered 61 SlRBP1-associated RNAs, most of which are involved in photosynthesis. SlRBP1 binding to selected target RNAs was validated by nRIP-qPCR. Intriguingly, the accumulation of proteins encoded by SlRBP1-bound transcripts, but not the mRNAs themselves, was reduced in slrbp1 mutants. Polysome profiling followed by RT-qPCR assays indicated that the polysome occupancy of target RNAs was lower in slrbp1 plants than in wild-type. Furthermore, SlRBP1 interacted with the eukaryotic translation initiation factor SleIF4A2. Silencing of SlRBP1 significantly reduced SleIF4A2 binding to SlRBP1-target RNAs. Taking these observations together, we propose that SlRBP1 binds to and channels RNAs onto the SleIF4A2 translation initiation complex and promotes the translation of its target RNAs to regulate chloroplast functions.

The use of high-sensitivity cardiac troponin T and creatinine kinase-MB as a prognostic markers in patients with acute myocardial infarction and chronic kidney disease.

Background: High-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase (CK)-MB are the most commonly used biomarkers for the diagnosis and prognosis of acute myocardial infarction (AMI). Chronic kidney disease (CKD) often leads to elevated hs-cTnT levels in non-AMI patients. However, studies comparing the prognostic value of both hs-cTnT and CK-MB in patients with AMI and CKD are lacking.Methods: We conducted a retrospective study on AMI patients diagnosed between January 2015 and October 2020. Patients were categorized based on renal function as normal or CKD. Peak hs-cTnT and CK-MB levels during hospitalization were collected, and their diagnostic value was evaluated using receiver operating characteristic (ROC) curves. The impact on in-hospital mortality was analyzed using multivariate logistic regression. The relationship between the hs-cTnT/CK-MB ratio and in-hospital death was examined using a restricted cubic spline (RCS) curve.Results: The study included 5022 AMI patients, of whom 797 (15.9%) had CKD. The AUCs of Hs-cTnT and CK-MB were higher in the CKD group [0.842 (95% CI: 0.789-0.894) and 0.821 (95% CI: 0.760-0.882)] than in the normal renal function group [0.695 (95% CI: 0.604-0.790) and 0.708 (95% CI: 0.624-0.793)]. After full adjustment for all risk factors, hs-cTnT (OR, 2.82; 95% CI, 1.03-9.86; p = 0.038) and CK-MB (OR, 4.91; 95% CI, 1.54-14.68; p = 0.007) above the cutoff values were independent predictors of in-hospital mortality in patients with CKD. However, in patients with normal renal function, only CK-MB above the cutoff (OR, 2.45; 95% CI, 1.02-8.24; p = 0.046) was a predictor of in-hospital mortality, whereas hs-cTnT was not. There was an inverted V-shaped relationship between the hs-cTnT/CK-MB ratio and in-hospital mortality, with an inflection point of 19.61. The ratio within the second quartile (9.63-19.6) was an independent predictor of in-hospital mortality in patients with CKD (OR 5.3, 95% CI 1.66-16.86, p = 0.005).Conclusions: Hs-cTnT independently predicted in-hospital mortality in AMI patients with CKD, whereas its predictive value was not observed in patients with normal renal function. CK-MB was an independent predictor of in-hospital mortality regardless of renal function. Moreover, the hs-cTnT/CK-MB ratio may aid in risk stratification of AMI patients with CKD.

[Investigating the impact of silencing an RNA-binding protein gene SlRBP1 on tomato photosynthesis through RNA-sequencing analysis].

Photosynthesis in plants directly affects the synthesis and accumulation of organic matter, which directly influences crop yield. RNA-binding proteins (RBPs) are involved in the regulation of a variety of physiological functions in plants, while the functions of RBPs in photosynthesis have not been clearly elucidated. To investigate the effect of a glycine-rich RNA-binding protein (SlRBP1) in tomato on plant photosynthesis, a stably inherited SlRBP1 silenced plant in Alisa Craig was obtained by plant tissue culture using artificial small RNA interference. It turns out that the size of the tomato fruit was reduced and leaves significantly turned yellow. Chlorophyll(Chl) content measurement, Chl fluorescence imaging and chloroplast transmission electron microscopy revealed that the chloroplast morphology and structure of the leaves of tomato amiR-SlRBP1 silenced plants were disrupted, and the chlorophyll content was significantly reduced. Measurement of photosynthesis rate of wild-type and amiR-SlRBP1 silenced plants in the same period demonstrated that the photosynthetic rate of these plants was significantly reduced, and analysis of RNA-seq data indicated that silencing of SlRBP1 significantly reduced the expression of photosynthesis-related genes, such as PsaE, PsaL, and PsbY, and affected the yield of tomato fruits through photosynthesis.

Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics.

Small-cell lung cancer (SCLC) has a poor prognosis and can be diagnosed with systemic metastases. Nevertheless, the molecular mechanisms underlying the development of SCLC are unclear, requiring further investigation. The current research aims to identify relevant biomarkers and available drugs to treat SCLC. The bioinformatics analysis comprised three Gene Expression Omnibus datasets (including GSE2149507, GSE6044, and GSE30219). Using the limma R package, we discovered differentially expressed genes (DEGs) in the current work. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were made by adopting the DAVID website. The DEG protein-protein interaction network was built based on the Search Tool for the Retrieval of Interacting Genes/Proteins website and visualized using the CytoHubba plugin in Cytoscape, aiming to screen the top ten hub genes. Quantitative real-time polymerase chain reaction was adopted for verifying the level of the top ten hub genes. Finally, the potential drugs were screened and identified using the QuartataWeb database. Totally 195 upregulated and 167 downregulated DEGs were determined. The ten hub genes were NCAPG, BUB1B, TOP2A, CCNA2, NUSAP1, UBE2C, AURKB, RRM2, CDK1, and KIF11. Ten FDA-approved drugs were screened. Finally, two genes and related drugs screened could be the prospective drug targets for SCLC treatment.

Cost-effectiveness of osimertinib versus placebo in resected EGFR-mutated non-small cell lung cancer in China.

PURPOSE: We aim to assess whether osimertinib postoperative adjuvant therapy, compared with placebo, is cost-effective in China. METHODS: We set up the Markov model that contains three health states over a 20-year period. Data were collected from the ADAURA trial that included transition probabilities and safety data. Through the analysis of literature and local charges, we explore both the cost and utility values. Sensitivity analyses were employed using TreeAge Pro software to access model stability. FINDINGS: Patients in the osimertinib group had 1.46 more Quality-adjusted Life Years (8.45 QALYs vs 6.99 QALYs) than the placebo group at an incremental cost of $14098.51($39962.99 vs $25864.48). Compared with the placebo group, the treatment strategy with osimertinib postoperative adjuvant therapy had an incremental cost-effectiveness ratio of $9661.97/QALY. The probability of the osimertinib-assisted therapy strategy being cost-effective will reach 100% if the threshold of willingness to pay is above $15,000/QALY. IMPLICATIONS: From the perspective of the Chinese Healthcare System, the treatment strategy with osimertinib postoperative adjuvant therapy is more cost-effective than the placebo strategy.

A Modified Model for Preoperatively Predicting Malignancy of Solitary Pulmonary Nodules: An Asia Cohort Study.

BACKGROUND: With the recent widespread use of computed tomography, interest in ground glass opacity pulmonary lesions has increased. We aimed to develop a model for predicting the probability of malignancy in solitary pulmonary nodules. METHODS: We assessed 846 patients with newly discovered solitary pulmonary nodules referred to Fujian Medical University Union Hospital. Data on 18 clinical and 13 radiologic variables were collected. Two thirds of the patients were randomly selected to derive the prediction model (derivation set); the remaining one third provided a validation set. The lesions were divided according to proportion of ground glass opacity (less than 50% or 50% or greater). Univariate analysis of significant covariates for their relationship to the presence of malignancy was performed. An equation expressing the probability of malignancy was derived from these findings and tested on data from the validation group. Receiver-operating characteristic curves were constructed using the prediction model and the Mayo Clinic model. RESULTS: In lesions with less than 50% ground glass opacity, three clinical characteristics (age, presence of symptoms, total protein) and three radiologic characteristics (diameter, lobulation, calcified nodes) were independent predictors of malignancy. In lesions with 50% or more ground glass opacity, two clinical characteristics (sex, percent of forced expiratory volume in 1 second accounting for expected value) and two radiologic characteristics (diameter, calcified nodes) were independent predictors of malignancy. Our prediction model was better than the Mayo Clinic model to distinguish between benign and malignant solitary pulmonary nodules (p < 0.05). CONCLUSIONS: Our prediction model could accurately identify malignancy in patients with solitary pulmonary nodules, especially in lesions with 50% or more ground glass opacity.

Shape selective plate-form Ga(2)O(3) with strong metal-support interaction to overlying Pd for hydrogenation of CO(2) to CH(3)OH.

A stronger metal-support interaction between Pd and plate-form Ga(2)O(3) nanocrystals covered with the predominant 002 surface than other Ga(2)O(3) surfaces is found, which gives higher methanol yield in catalytic CO(2) hydrogenation.