A novel diagnostic signature of circulating tsRNAs and miRNAs in esophageal squamous cell carcinoma detected with a microfluidic platform.

Small non-coding RNAs (sncRNAs) consisting of tRNA-derived small RNAs (tsRNAs) and miRNAs can be released by cancer cells and detected in blood, offering great potential for diagnosis of malignant tumors such as squamous cell carcinoma of the esophagus (ESCC). One of the major challenges for the clinical application of blood-based sncRNAs biomarkers is the difficulty of detection because of their small sncRNA size and low abundance. The deferentially expressed tsRNAs and miRNAs in plasma were studied with high-throughput sequencing and polymerase chain reaction in ESCC cohorts. A novel signature containing tRF-55:74-chrM.Phe-GAA, tRF-56:75-Ala-CGC-1-M4 and miR-4488 was identified with diagnostic potential. The signature was further confirmed by an attomolar-level ultrasensitive and rapid microfluidic biochip, which can achieve a multiplex, simple and low-cost detection. Our results indicated that a combination of tsRNAs and miRNAs has high diagnostic efficiency and tremendous potential to act as specific biomarkers through a reliable, highly sensitive, fast, and economic microfluidic biochip for ESCC diagnosis.

CMR left ventricular strains beyond global longitudinal strain in differentiating light-chain cardiac amyloidosis from hypertrophic cardiomyopathy.

Background: The clinical value of left ventricular (LV) global longitudinal strain (GLS) in the differential diagnosis of light-chain cardiac amyloidosis (AL-CA) and hypertrophic cardiomyopathy (HCM) has been previously reported. In this study, we analyzed the potential clinical value of the LV long-axis strain (LAS) to discriminate AL-CA from HCM. Furthermore, we analyzed the association between all the LV global strain parameters derived from cardiac magnetic resonance (CMR) feature tracking and LAS in both the AL-CA and HCM patients to assess the differential diagnostic efficacies of these global peak systolic strains. Materials and methods: Thus, this study enrolled 89 participants who underwent cardiac MRI (CMRI), consisting of 30 AL-CA patients, 30 HCM patients, and 29 healthy controls. The intra- and inter-observer reproducibility of the LV strain parameters including GLS, global circumferential strain (GCS), global radial strain (GRS), and LAS were assessed in all the groups and compared. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic performances of the CMR strain parameters in discriminating AL-CA from HCM. Results: The intra- and inter-observer reproducibility of the LV global strains and LAS were excellent (range of interclass correlation coefficients: 0.907-0.965). ROC curve analyses showed that the differential diagnostic performances of the global strains in discriminating AL-CA from HCM were good to excellent (GRS, AUC = 0.921; GCS, AUC = 0.914; GLS, AUC = 0.832). Furthermore, among all the strain parameters analyzed, LAS showed the highest diagnostic efficacy in differentiating between AL-CA and HCM (AUC = 0.962). Conclusion: CMRI-derived strain parameters such as GLS, LAS, GRS, and GCS are promising diagnostic indicators that distinguish AL-CA from HCM with high accuracy. LAS showed the highest diagnostic accuracy among all the strain parameters.

The value of enhanced CT features and texture-signatures in assessing the inflammatory infiltration of pancreatic ductal adenocarcinoma.

Purpose: To explore the predictive value of computed tomography (CT) imaging features and CT-based texture analysis in assessing inflammatory infiltration in pancreatic ductal adenocarcinoma (PDAC). Methods: A total of 43 patients with PDAC confirmed by surgical pathology were included in the study. The clinical, radiological, surgical, and pathological features of the patients were analyzed retrospectively using the chi-square test or Spearman's correlation. Receiver operating characteristic (ROC) curves were utilized to assess the overall predictive ability of the tumor enhancement degree on triphasic contrast-enhanced CT images for the inflammatory infiltration degree in PDAC. Furthermore, all CT data were uploaded to the RadCloud platform for region of interest (ROI) delineation and feature extraction. Then, the Variance Threshold and SelectKBest algorithms were used to find the optimal CT features. Binary logistic regression was employed to analyze the selected features in all three contrast-enhanced CT phases, and regression equations were formulated. ROC analysis was performed to evaluate the predictive effectiveness of each equation. Results: The analysis revealed a statistically significant correlation between the degree of differentiation and radiological findings such as necrosis and cystic degeneration, vascular invasion, and the presence of ascites (P < 0.05). The enhancement degree of the tumor in both the arterial and venous phases was significantly correlated with the inflammatory infiltration degree (P < 0.05); however, the areas under the ROC curve (AUCs) of arterial and venous enhancement were 0.570 and 0.542, respectively. Regression equations based on the texture features of triphasic contrast-enhanced tumors were formulated, and their AUCs were 0.982, 0.643, and 0.849. Conclusion: Conventional radiological features are not significantly correlated with the degree of inflammatory infiltration in PDAC. The enhancement degrees in both the arterial phase and venous phase were statistically correlated with the inflammatory infiltration level but had poor predictive value. The texture features of PDAC on contrast-enhanced CT may show a better assessment value, especially in the arterial phase.

Cyclosporin A acts as a novel insecticide against Cry1Ac-susceptible and -resistant Helicoverpa armigera.

Cotton bollworm (Helicoverpa armigera) is an economically important pest, which is difficult to manage due to its biological and ecological traits, and resistance to most insecticides. Alternative compounds for the sustainable management of H. armigera are needed. As a fungal metabolite, Cyclosporin A (CsA) has not been applied in agriculture pests. Here, CsA was evaluated as a propective insecticide for H. armigera. The results showed that CsA displayed high insecticidal activity against both Cry1Ac-susceptible and -resistant populations of H. armigera. Moreover, lower concentrations of CsA had clear effects, including significantly reduced pupal weight, pupation rate, emergence rate, ovary size, female fecundity and egg hatchability. Further study confirmed that CsA suppressed calcineurin activity and the subsequent expression of endogenous antimicrobial peptide genes (APMs), leading to impaired immunity, ultimately resulting in delayed development and increased mortality. Thus, CsA treatment could control the cotton bollworm population and even showed efficacy against those with Bt resistance. In addition, the morphological changes observed in insects fed CsA with lower concentrations provide insight into insect immunity, regulation of growth and development, regulation of body color, ovary development and sexual selection under external pressure. Overall, our study provides information on biological control potential of Cry1Ac-susceptible and -resistant populations of H. armigera to develop novel bioinsecticides.

Cyclosporin A as a Potential Insecticide to Control the Asian Corn Borer Ostrinia furnacalis Guenée (Lepidoptera: Pyralidae).

The long-term use of chemical insecticides has caused serious problems of insect resistance and environmental pollution; new insecticides are needed to solve this problem. Cyclosporin A (CsA) is a polypeptide produced by many fungi, which is used to prevent or treat immune rejection during organ transplantation. However, little is known about the utility of CsA as an insecticide. Therefore, this study evaluated the insecticidal activity of CsA using Ostrinia furnacalis as a model. The results demonstrated that CsA was toxic to O. furnacalis with LC50 values of 113.02 µg/g and 198.70 µg/g for newly hatched neonates and newly molted third-instar larvae, respectively. Furthermore, CsA treatment had sublethal effects on the development of O. furnacalis, and significantly reduced the fecundity of adults; this suggests that CsA has great potential to suppress O. furnacalis populations. Further analysis revealed that CsA suppressed calcineurin activity in larvae. CsA had independent or synergistic toxic effects on O. furnacalis when combined with ß-cypermethrin, indoxacarb, emamectin benzoate, azadirachtin, and the Bacillus thuringiensis toxin Cry1Ac, which suggests that CsA can help prevent or manage resistance. Our study provides detailed information on the potential of CsA as an insecticide for controlling lepidopterans.

Cyclosporin A as a Source for a Novel Insecticidal Product for Controlling Spodoptera frugiperda.

The fall armyworm (FAW), Spodoptera frugiperda, causes substantial annual agricultural production losses worldwide due to its resistance to many insecticides. Therefore, new insecticides are urgently needed to more effectively control FAW. Cyclosporin A (CsA) is a secondary metabolite of fungi; little is known about its insecticidal activity, especially for the control of FAW. In this study, we demonstrate that CsA shows excellent insecticidal activity (LC50 = 9.69 µg/g) against FAW through significant suppression of calcineurin (CaN) activity, which is a new target for pest control. Combinations of CsA and indoxacarb, emamectin benzoate, or Vip3Aa showed independent or synergistic toxicity against FAW; however, the combination of CsA and chlorantraniliprole showed no toxicity. Sublethal doses of CsA led to decreases in FAW larval and pupal weight, pupation, emergence, mating rates, adult longevity, extended development of FAW larvae and pupae and the pre-oviposition period of adults, and increases in the proportion of pupal malformation. Importantly, CsA treatment reduced FAW ovarian size and female fecundity, which suggests that it has great potential to suppress FAW colony formation. Taken together, these results indicate that CsA has high potential as an insecticide for controlling FAW.

A signature-based classification of lung adenocarcinoma that stratifies tumor immunity.

Background: Immune-related subgroup classification in immune checkpoint blockade (ICB) therapy is largely inconclusive in lung adenocarcinoma (LUAD). Materials and methods: First, the single-sample Gene Set Enrichment Analysis (ssGSEA) and K-means algorithms were used to identify immune-based subtypes for the LUAD cohort based on the immunogenomic profiling of 29 immune signatures from The Cancer Genome Atlas (TCGA) database (n = 504). Second, we examined the prognostic and predictive value of immune-based subtypes using bioinformatics analysis. Survival analysis and additional COX proportional hazards regression analysis were conducted for LUAD. Then, the immune score, tumor-infiltrating immune cells (TIICs), and immune checkpoint expression of the three subtypes were analyzed. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) of the differentially expressed genes (DEGs) between three immune-based subtypes were subsequently analyzed for functional enrichment pathways. Result: A total of three immune-based subtypes with distinct immune signatures have been identified for LUAD and designated as cluster 1 (C1), cluster 2 (C2), and cluster 3 (C3). Patients in C3 had higher stromal, immune, and ESTIMATE scores, whereas those in C1 had the opposite. Patients in C1 had an enrichment of macrophages M0 and activation of dendritic cells, whereas tumors in C3 had an enrichment of CD8+ T cells, activation of CD4+ memory T cells, and macrophages M1. C3 had a higher immune cell infiltration and a better survival prognosis than other subtypes. Furthermore, patients in C3 had higher expression levels of immune checkpoint proteins such as PD-L1, PD1, CTLA4, LAG3, IDO1, and HAVCR2. No significant differences were found in cluster TMB scores. We also found that immune-related pathways were enriched in C3. Conclusion: LUAD subtypes based on immune signatures may aid in the development of novel treatment strategies for LUAD.