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Isoliquiritigenin (ISL) exhibits antioxidation and anti-inflammation activity. We sought to investigate the effects and mechanism of ISL on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE -/- ) mice. Firstly, we determined that ISL reduced the mRNA levels of inflammatory factors interleukin 6 ( IL-6 ), tumor necrosis factor α ( TNF-α ), and monocyte chemotactic protein-1 ( MCP-1 ), while it increased the expression of several lipoprotein-related genes in peritoneal macrophages treated with lipopolysaccharide (LPS). ISL also enhanced peroxisome proliferator-activated receptor gamma (PPARγ) protein levels and reversed the changes of ATP-binding cassette transporter A (ABCA1) and cluster of differentiation 36 (CD36) in macrophages treated with oxidative low-density lipoprotein (ox-LDL). Then, in an in vivo study, female apoE -/- mice were fed a Western diet with ISL (0, 20, 100 mg/kg/day) added for 12 weeks. We found that ISL decreased the plasma cholesterol levels of very low-density lipoprotein (VLDL)/LDL, promoted plasma superoxide dismutase (SOD) and paraoxonase-1 (PON1) activities, and decreased plasma IL-6, TNF-α, and MCP-1 levels. Moreover, ISL significantly reduced the atherosclerotic lesions and hepatic steatosis in apoE -/- mice. In the liver, ISL altered the expression of several key genes (such as SRBI , ABCA1 , ABCG8 , PPARγ , and FASN ) involving cholesterol-selective uptake and excretion into bile, triglyceride (TG) biosynthesis, and inflammation. These results suggest that the atheroprotective effects of ISL are due to the improvement of lipid metabolism, antioxidation, and anti-inflammation, which involve PPARγ-dependent signaling., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Several Pleurocordyceps species have been reported as hyperparasitic fungi. A new species, Pleurocordyceps fusiformispora, and a known species, Perennicordyceps elaphomyceticola, are described here based on morphology and phylogenetic evidence from six genes (ITS, SSU, LSU, TET1-α, RPB1, and RPB2). Pl. fusiformispora differed from the other Pleurocordyceps species by producing flaky colonies, ovoid or elliptic α-conidia, and fusiform or long fusiform β-conidia. Both full genomes of Pe. elaphomyceticola and Pl. fusiformispora were sequenced, annotated, and compared. The antiSMASH and local BLAST analyses revealed significant differences in the number and types of putative secondary metabolite biosynthetic gene clusters, i.e., NPPS, PKS, and hybrid PKS–NRPS domains, between the two species. In addition, the putative BGCs of six compounds, namely ε-poly lysine, 4-epi-15-epi-brefeldin A, Monorden D/monocillin IV/monocillin VII/pochonin M/monocillin V/monocillin II, Tolypyridone, Piperazine, and Triticone DABFC, were excavated in the present study. This study motivates the use of heterologous expression and gene knockout methods to discover novel biologically active SMs from Polycephalomycetaceae. [ABSTRACT FROM AUTHOR]

Whole genomes of Samsoniella hepiali ICMM 82-2 and S. yunnanensis YFCC 1527 were sequenced and annotated, as well as compared with whole genome sequences of other species in the family Cordycipitaceae. S. hepiali ICMM 82-2, S. hepiali FENG and S. yunnanensis YFCC 1527 had 54, 57 and 58 putative secondary metabolite biosynthetic gene clusters, respectively. S. hepiali had one unique domain and S. yunnanensis YFCC 1527 six. Both S. hepiali and S. yunnanensis YFCC 1527 had curvupallide-B, fumosorinone and fujikurin putative biosynthetic gene clusters. C. javanica had biosynthetic gene clusters for fumonisin. The 14 genomes had common domains, namely A-P-C-P-C and KS-AT-DH-ER-KR-ACP. The A-P-C-P-C domain may be involved in the biosynthesis of dimethylcoprogen. The maximum likelihood and the Bayesian inference trees of KS-AT-DH-ER-KR-ACP were highly consistent with the multigene phylogenetic tree for the 13 species of Cordycipitaceae. This study facilitates the discovery of novel biologically active SMs from Cordycipitaceae using heterologous expression and gene knockdown methods. [ABSTRACT FROM AUTHOR]

Simple Summary: Esophageal squamous cell carcinoma (ESCC) is a malignancy characterized by high mortality and dismal quality of life. Circulating tumor cells (CTCs), considered precursors of distant metastasis, can be analyzed using a non-invasive liquid biopsy approach to identify patients at risk of cancer progression or recurrence. The current study employed an unbiased size-based CTC enrichment strategy in combination with quantitative reverse transcription polymerase chain reaction (RT-qPCR) to investigate gene transcripts as potential biomarkers in the bloodstream. We categorized 83.6% (46/55) of ESCC patients as CTC-positive, each displaying at least two detected markers. Furthermore, 50.9% (28/55) of ESCC patients were identified as CTC-high, showing at least five detected markers using a 10-gene CTC panel. The presence of specific markers, namely TWIST1, VEGFC, CCND1, and TFRC, was significantly associated with shorter survival of the patients, suggesting their prognostic values as liquid biopsy markers to guide clinical ESCC treatment decisions and enhance treatment efficacy. We investigated the clinical significance of CTCs in cancer progression by detecting multiple cancer driver genes associated with epithelial-to-mesenchymal transition (EMT) at the transcript level. The 10-gene panel, comprising CCND1, ECT2, EpCAM, FSCN1, KRT5, KRT18, MET, TFRC, TWIST1, and VEGFC, was established for characterizing CTCs from mouse ESCC xenograft models and clinical ESCC peripheral blood (PB) samples. Correlations between gene expression in CTCs from PB samples (n = 77) and clinicopathological features in ESCC patients (n = 55) were examined. The presence of CTCs at baseline was significantly correlated with tumor size (p = 0.031). The CTC-high patients were significantly correlated with advanced cancer stages (p = 0.013) and distant metastasis (p = 0.029). High mRNA levels of TWIST1 (Hazard Ratio (HR) = 5.44, p = 0.007), VEGFC (HR = 6.67, p < 0.001), TFRC (HR = 2.63, p = 0.034), and EpCAM (HR = 2.53, p = 0.041) at baseline were significantly associated with a shorter overall survival (OS) in ESCC patients. This study also revealed that TWIST1 facilitates EMT and enhances malignant potential by promoting tumor migration, invasion, and cisplatin chemoresistance through the TWIST1-TGFBI-ZEB1 axis in ESCC, highlighting the prognostic and therapeutic potential of TWIST1 in clinical ESCC treatment. [ABSTRACT FROM AUTHOR]

The stability and Hopf bifurcation of gene expression models with a mechanism of delayed state feedback are considered. An effective algorithm for the calculations on the delay stable interval of the equilibrium point, the direction, and stability of the bifurcating periodic solution is also proposed. The τ -decomposition strategy is applied to tackle the issue of local stability, and the explicit formula for the delay stable interval is provided. In addition, the asymptotical behaviors of the bifurcation solutions are investigated by the center manifold theorem and normal form theory. The direction and stability of the Hopf bifurcation are determined naturally. In addition, a subtle bilinear form of the adjoint system is proposed to calculate the bifurcation parameters directly. Finally, the correctness and effectiveness of our results and algorithm are verified by typical numerical examples. [ABSTRACT FROM AUTHOR]

Simple Summary: Quantitative real-time fluorescent polymerase chain reaction (qRT-PCR) is a momentous tool for calculating the expression levels of targeted genes across various experimental conditions. The selection and evaluation of stable reference genes for qRT-PCR analysis is an essential precondition for reliable expression assessment. Phthorimaea operculella is one of the most serious Lepidopteran pests that attack potatoes around the world. In the present paper, a total of 10 commonly used reference genes, namely ACT, α-TUB, 18S, 28S, GAPDH, EF1α, RPL4, RPL13, RPL27 and SOD, were selected and validated for suitability under three treatments (developmental stages, tissues/organs and temperatures) using five methods (Ct value, geNorm, NormFinder, BestKeeper and RefFinder). These results indicated that EF1α and RPL13 were the best suitable reference genes for diverse backgrounds. The relative transcript levels of the target gene chitin synthase A gene (PoChSA) were abundantly expressed in epidermal cells, and lowly transcribed in the midgut. Our findings will be beneficial for improving the accuracy of qRT-PCR analysis for future functional analysis of the target gene expression in P. operculella. Due to a lack of effective internal references, studies on functional genes in Phthorimaea operculella, a serious Lepidopteran pest attacking potatoes worldwide, have been greatly limited. To select suitable endogenous controls, ten housekeeping genes of actin (ACT), α-tubulin (α-TUB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), elongation factor 1α (EF1α), 18S and 28S ribosomal RNA (18S, 28S), ribosomal protein genes RPL4, RPL13 and RPL27 and superoxide dismutase (SOD) were tested. Their expression levels were determined under three different experimental conditions (developmental stages, tissues/organs and temperatures) using qRT-PCR technology. The stability was evaluated with five methods (Ct value, geNorm, NormFinder, BestKeeper and RefFinder). The results clarified that RPL13, EF1α and RPL27 are ranked as the best reference gene combination for measuring gene expression levels among different developing stages and under various temperatures; EF1α and RPL13 are recommended to normalize the gene expression levels among diverse tissues. EF1α and RPL13 are the best reference genes in all the experimental conditions. To validate the utility of the selected reference pair, EF1α and RPL13, we estimated the tissue-biased expression level of chitin synthase A gene (PoChSA). As expected, PoChSA was abundantly expressed in ectodermally derived epidermal cells, and lowly transcribed in the midgut. These findings will lay the foundation for future research on the molecular physiology and biochemistry of P. operculella. [ABSTRACT FROM AUTHOR]

Simple Summary: Prognosis for patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor mainly due to late diagnosis and limited curative treatment options. Neoadjuvant chemoradiotherapy (nCRT) plus surgery is considered the standard of care for patients with locally advanced ESCC. Currently, predicting prognosis remains a challenging task. Quantitative imaging radiomics analysis has shown promising results, but these methods are traditionally data-intensive, requiring a large sample size, and are not necessarily based on the underlying biology. Feature selection based on genomics is proposed in this work, leveraging differentially expressed genes to reduce the number of radiomic features allowing for the creation of a CT-based radiomic model using the genomics-based feature selection method. The established radiomic signature was prognostic for patients' long-term survival. The radiomic nomogram could provide a valuable prediction for individualized long-term survival. Purpose: To evaluate the prognostic value of baseline and restaging CT-based radiomics with features associated with gene expression in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiation (nCRT) plus surgery. Methods: We enrolled 106 ESCC patients receiving nCRT from two institutions. Gene expression profiles of 28 patients in the training set were used to detect differentially expressed (DE) genes between patients with and without relapse. Radiomic features that were correlated to DE genes were selected, followed by additional machine learning selection. A radiomic nomogram for disease-free survival (DFS) prediction incorporating the radiomic signature and prognostic clinical characteristics was established for DFS estimation and validated. Results: The radiomic signature with DE genes feature selection achieved better performance for DFS prediction than without. The nomogram incorporating the radiomic signature and lymph nodal status significantly stratified patients into high and low-risk groups for DFS (p < 0.001). The areas under the curve (AUCs) for predicting 5-year DFS were 0.912 in the training set, 0.852 in the internal test set, 0.769 in the external test set. Conclusions: Genomics association was useful for radiomic feature selection. The established radiomic signature was prognostic for DFS. The radiomic nomogram could provide a valuable prediction for individualized long-term survival. [ABSTRACT FROM AUTHOR]