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Salusin-β is a biologically active peptide, which plays an important role in promoting atherosclerosis, raising blood pressure, promoting cardiomyocyte hypertrophy, participating in vascular smooth muscle cell proliferation and anti-inflammatory response. Salusin-β has certain predictive value for the prognosis of cardiovascular diseases, it is expected to find targets and thus support the treatment of cardiovascular diseases.

SUMMARY: Abscisic acid (ABA) is involved in salt and drought stress responses, but the underlying molecular mechanism remains unclear. Here, we demonstrated that the overexpression of MdMYB44‐like, an R2R3‐MYB transcription factor, significantly increases the salt and drought tolerance of transgenic apples and Arabidopsis. MdMYB44‐like inhibits the transcription of MdPP2CA, which encodes a type 2C protein phosphatase that acts as a negative regulator in the ABA response, thereby enhancing ABA signaling‐mediated salt and drought tolerance. Furthermore, we found that MdMYB44‐like and MdPYL8, an ABA receptor, form a protein complex that further enhances the transcriptional inhibition of the MdPP2CA promoter by MdMYB44‐like. Significantly, we discovered that MdPP2CA can interfere with the physical association between MdMYB44‐like and MdPYL8 in the presence of ABA, partially blocking the inhibitory effect of the MdMYB44‐like–MdPYL8 complex on the MdPP2CA promoter. Thus, MdMYB44‐like, MdPYL8, and MdPP2CA form a regulatory loop that tightly modulates ABA signaling homeostasis under salt and drought stress. Our data reveal that MdMYB44‐like precisely modulates ABA‐mediated salt and drought tolerance in apples through the MdPYL8–MdPP2CA module. Significance Statement: Under salt and drought stress, ABA promotes MdMYB44‐like gene expression, and MdPYL8 interacts with MdMYB44‐like to form a protein complex that further strengthens the transcriptional inhibition of MdMYB44‐like on the MdPP2CA promoter. Interestingly, MdPP2CA interferes with the interaction between MdMYB44‐like and MdPYL8 in the presence of ABA, thereby reducing the transcriptional inhibition of MdPP2CA by the MdMYB44‐like‐MdPYL8 complex and thus balancing ABA signaling in plants. [ABSTRACT FROM AUTHOR]

Background: The low level of circulating tumor DNA (ctDNA) in the blood is a well-known challenge for the application of liquid biopsies in early-stage non-small cell lung cancer (NSCLC) management. Studies of metastatic NSCLC indicate that ctDNA levels are associated with tumor metabolic activity as measured by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT). This study investigated this association in NSCLC patients considered for potentially curative treatment and explored whether the two methods provide independent prognostic information. Method: Patients with stage I-III NSCLC who had routinely undergone an 18F-FDG PET/CT scan and exploratory ctDNA analyses were included. Tumor glucose uptake was measured by maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) from the 18F-FDG PET/CT scans. ctDNA detectability and quantity, using variant allele frequency, were estimated by tumor-informed ctDNA analyses. Results: In total, 63 patients (median age 70 years, 60% women, and 90% adenocarcinoma) were included. The tumor glucose uptake (SUVmax, MTV, and TLG) was significantly higher in patients with detectable ctDNA (n = 19, p < 0.001). The ctDNA quantity correlated with MTV (Spearman's ρ = 0.53, p = 0.021) and TLG (Spearman's ρ = 0.56, p = 0.013) but not with SUVmax (Spearman's ρ = 0.034, p = 0.15). ctDNA detection was associated with shorter OS independent of MTV (HR: 2.70, 95% CI: 1.07–6.82, p = 0.035) and TLG (HR: 2.63, 95% CI: 1.06–6.51, p = 0.036). Patients with high tumor glucose uptake and detectable ctDNA had shorter overall survival and progression-free survival than those without detectable ctDNA, though these associations were not statistically significant (p > 0.05). Conclusion: There was a positive correlation between plasma ctDNA quantity and MTV and TLG in early-stage NSCLC patients. Despite the correlation, the results indicated that ctDNA detection was a negative prognostic factor independent of MTV and TLG. [ABSTRACT FROM AUTHOR]

(1) Background: Analysis of tumor DNA by next-generation sequencing (NGS) plays various roles in the classification and management of cancer. This study aimed to assess the performance of two similar and large, comprehensive gene panels with a focus on clinically relevant variant detection and tumor mutation burden (TMB) assessment; (2) Methods: DNA from 19 diagnostic small cell lung cancer biopsies and an AcroMetrix™ assessment sample with >500 mutations were sequenced using Oncomine™ Comprehensive Assay Plus (OCAP) on the Ion Torrent platform and TruSight Oncology 500 Assay (TSO500) on the Illumina platform; (3) Results: OCAP and TSO500 achieved comparable NGS quality, such as mean read coverage and mean coverage uniformity. A total of 100% of the variants in the diagnostic samples and 80% of the variants in the AcroMetrix™ assessment sample were detected by both panels, and the panels reported highly similar variant allele frequency. A proportion of 14/19 (74%) samples were classified in the same TMB category; (4) Conclusions: Comparable results were obtained using OCAP and TSO500, suggesting that both panels could be applied to screen patients for enrolment in personalized cancer treatment trials. [ABSTRACT FROM AUTHOR]

Droplet digital polymerase chain reaction (ddPCR) is a highly sensitive and accurate method for quantification of nucleic acid sequences. We used absolute quantification of mutated v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homology gene (KRAS) by ddPCR to investigate the prognostic role of mutated KRAS in patients with KRAS‐mutated lung adenocarcinomas. Pre‐treatment plasma samples from 60 patients with stages I–IV KRAS‐mutated lung adenocarcinomas were analysed for KRAS mutations. The associations between survival, detectable KRAS mutations in plasma, and the plasma concentration of mutated KRAS were assessed. Overall, 23 of 60 (38%) patients had detectable KRAS mutation in plasma. The percentage of patients with detectable mutation was 8% in stage I, 30% in stage II, 71% in stage III, and 73% in stage IV. Estimated overall median progression‐free survival (PFS) and overall survival (OS) were 26.2 months [95% confidence interval (CI) 12.5–39.9] and 50.8 months (95% CI 0–107.3), respectively. Patients with detectable mutations in plasma had significantly worse median PFS compared to patients with undetectable mutation (13.1 versus 70.1 months) and shorter median OS (20.7 versus not reached). High circulating tumour DNA (ctDNA) concentrations of mutated KRAS were significantly associated with shorter PFS [hazard ratio (HR) 1.008, 95% CI 1.004–1.012] and OS (HR 1.007, 95% CI 1.003–1.011). All associations remained statistically significant in multivariable analyses. In conclusion, ddPCR is an accurate and easily feasible technique for quantification of KRAS mutations in ctDNA. The presence of detectable KRAS mutation in plasma at baseline was associated with worse PFS and OS. High concentration of mutated KRAS in ctDNA was an independent negative prognostic factor for both PFS and OS. [ABSTRACT FROM AUTHOR]