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Parageobacillus thermoglucosidasius is emerging as a highly promising thermophilic organism for metabolic engineering. The utilization of CRISPR-Cas technologies has facilitated programmable genetic manipulation in P. thermoglucosidasius. However, the absence of thermostable NHEJ enzymes limited the capability of the endogenous type I CRISPR-Cas system to generate a variety of extensive genomic deletions. Here, two thermophilic NHEJ enzymes were identified and combined with the endogenous type I CRISPR-Cas system to develop a genetic manipulation tool that can achieve long-range genomic deletion across various lengths. By optimizing this tool—through adjusting the expression level of NHEJ enzymes and leveraging our discovery of a negative correlation between GC content of the guide RNA (gRNA) and deletion efficacy—we streamlined a comprehensive gRNA selection manual for whole-genome editing, achieving a 100 % success rate in randomly selecting gRNAs. Notably, using just one gRNA, we achieved genomic deletions spanning diverse length, exceeding 200 kilobases. This tool will facilitate the genomic manipulation of P. thermoglucosidasius for both fundamental research and applied engineering studies, further unlocking its potential as a thermophilic cell factory.

In this study, the high-temperature performance of hypersonic missile radomes was investigated through a combination of numerical simulations, experiments, and machine learning-based damage detection. Two- and three-dimensional steady-state and transient heat conduction models were developed in MATLAB and COMSOL to examine the effects of different materials (ceramic, air and copper), filler configurations, and geometric shapes (cylindrical vs. conical) on radome insulation. Results indicated that introducing an air gap significantly reduced the peak temperature in the metallic layer (by up to 10–15 %), while shape optimization (e.g., cylindrical structures) further improved thermal uniformity. High-temperature damage simulations were performed using a Huffman Damage Coefficient, confirming that an air interlayer markedly decreased the damage area from 10 to 15 % to about 2–5 %. Laboratory tests employing infrared thermography validated the numerical predictions, showing consistency in temperature trends and structural integrity under ∼1000 °C heating. Furthermore, machine learning techniques (ResNet50) were applied to classify and detect microscopic damage, achieving a 95 % accuracy. These findings offer a robust theoretical and experimental basis for designing high-performance radomes and provide guidance for future integrated approaches to thermal protection in hypersonic missile systems.

Abstract Thermophilic cell factories have remarkably broad potential for industrial applications, but are limited by a lack of genetic manipulation tools and recalcitrance to transformation. Here, we identify a thermophilic type I-B CRISPR-Cas system from Parageobacillus thermoglucosidasius and find it displays highly efficient transcriptional repression or DNA cleavage activity that can be switched by adjusting crRNA length to less than or greater than 26 bp, respectively, without ablating Cas3 nuclease. We then develop an orthogonal tool for genome editing and transcriptional repression using this type I-B system in both thermophile and mesophile hosts. Empowered by this tool, we design a strategy to screen the genome-scale targets involved in transformation efficiency and established dynamically controlled supercompetent P. thermoglucosidasius cells with high efficiency ( ~ 108 CFU/μg DNA) by temporal multiplexed repression. We also demonstrate the construction of thermophilic riboflavin cell factory with hitherto highest titers in high temperature fermentation by genome-scale identification and combinatorial manipulation of multiple targets. This work enables diverse high-efficiency genetic manipulation in P. thermoglucosidasius and facilitates the engineering of thermophilic cell factories.

Abstract This paper explores the influence of fund managers’ social networks on the herding behavior of securities investment funds (SIFs) in China. Using the data of Chinese SIFs in recent years as a sample, it adopts the CSAD model to measure SIFs’ herding behavior. Combining indicators such as social network centrality, constraint, and size, it constructs a regression model of the influence of fund managers’ social networks on the herding behavior of SIFs and conducts an empirical study. The heterogeneity of this influence is investigated in four dimensions, degree of herding behavior, gender, diploma, and region. The results show that: (i) The larger the social network size of fund managers, the lower the degree of herding behavior of fund managers, but the effect of the network constraint on the degree of herding behavior is not significant. (ii) When the degree of herding behavior of SIFs is high, the effect of network size on herding behavior is heterogeneous. (iii) The relationship between the social network of male fund managers and the degree of herding behavior is more significant than that of female fund managers, as network size is significant for male fund managers, while the regression results of social network centrality, network constraint, network size, and the degree of herding behavior of female fund managers are all not significant. (iv) The social network of the fund manager with a master’s degree has a significant impact on the herding behavior of SIFs, which is not significant in fund managers with Ph.D.

Runting and stunting syndrome (RSS), which is characterized by lower body weight, widely occurs in broilers. Some RSS chickens simply exhibit slow growth without pathological changes. An increasing number of studies indicate that broiler strains differ in susceptibility to infectious diseases, most likely due to their genetic differences. The objective of this study was to detect the differentially expressed miRNAs and mRNAs in RSS and normal chickens. By integrating miRNA with mRNA expression profiling, potential molecular mechanisms involved in RSS could be further explored. Twenty-two known miRNAs and 1,159 genes were differentially expressed in RSS chickens compared with normal chickens (P < 0.05). qPCR validation results displayed similar patterns. The differentially expressed genes were primarily involved in energy metabolism pathways. The antisense transcripts were extensively expressed in chicken liver albeit with reduced abundance. Dual-luciferase reporter assay indicated that gga-miR-30b/c directly target CARS through binding to its 3'UTR. The miR-30b/c: CARS regulation mainly occurred in liver. In thigh muscle and the hypothalamus, miR-30b/c are expressed at higher levels in RSS chickens compared with normal chickens from 2 to 6 w of age, and notably significant differences are observed at 4 w of age.

ObjectiveThe aim of this study is the identification of hub genes associated with idiopathic pulmonary arterial hypertension (IPAH).Materials and MethodsGSE15197 gene expression data was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by screening IPAH patients and controls. The 5,000 genes with the greatest variances were analyzed using a weighted gene co-expression network analysis (WGCNA). Modules with the strongest correlation with IPAH were chosen, followed by a functional enrichment analysis. Protein–protein interaction (PPI) networks were constructed to identify hub gene candidates using calculated degrees. Real hub genes were found from the overlap of DEGs and candidate hub genes. microRNAs (miRNAs) targeting real hub genes were found by screening miRNet 2.0. The most important IPAH miRNAs were identified.ResultsThere were 4,395 DEGs identified. WGCNA indicated that green and brown modules associated most strongly with IPAH. Functional enrichment analysis showed that green and brown module genes were mainly involved in protein digestion and absorption and proteoglycans in cancer, respectively. The top ten candidate hub genes in green and brown modules were identified, respectively. After overlapping with DEGs, 11 real hub genes were identified: EP300, MMP2, CDH2, CDK2, GNG10, ALB, SMC2, DHX15, CUL3, BTBD1, and LTN1. These genes were expressed with significant differences in IPAH versus controls, indicating a high diagnostic ability. The miRNA–gene network showed that hsa-mir-1-3p could associate with IPAH.ConclusionEP300, MMP2, CDH2, CDK2, GNG10, ALB, SMC2, DHX15, CUL3, BTBD1, and LTN1 may play essential roles in IPAH. Predicted miRNA hsa-mir-1-3p could regulate gene expression in IPAH. Such hub genes may contribute to the pathology and progression in IPAH, providing potential diagnostic and therapeutic opportunities for IPAH patients.