Tanshinone IIA protects mouse testes from heat stress injury by inhibiting apoptosis and TGFß1/Smad2/Smad3 signaling pathway.

Heat stress can cause testicular damage and affect male fertility. Tanshinone IIA (TSA) is a monomer substance derived from plants, with antioxidant and anti-apoptotic effects. Whether it can repair testicular damage caused by heat stress is unclear. This study aims to construct a mouse testicular heat stress injury model and intervene with TSA. Various methods such as histopathology, high-throughput sequencing, bioinformatics analysis, and molecular biology were used to investigate whether TSA can alleviate heat stress-induced testicular injury and its mechanism. Results showed that heat stress significantly reduced the diameter of the mouse seminiferous tubules, increased cell apoptosis in the testicular tissue, and significantly decreased testosterone levels. After TSA intervention, testicular morphology and cell apoptosis improved significantly, and testosterone secretion function was restored. High-throughput transcriptome sequencing found that key differentially expressed genes between the HS group and the control and TSA groups clustered in the apoptosis and TGFß signaling pathways. Using western blot technology, we found that the HS group upregulated TGFß1/Smad2/Smad3 pathway protein expression, causing cell apoptosis, testicular tissue organic lesions, and affecting testicular secretion function. Through TSA intervention, we found that it can inhibit TGFß1/Smad2/Smad3 pathway protein expression, thereby restoring testicular damage caused by heat stress. This study confirms that TSA can effectively restore testicular damage caused by heat stress in mice, possibly by inhibiting the TGFß1/Smad2/Smad3 pathway to suppress apoptosis.

A novel competitive exact approach to solve assembly line balancing problems based on lexicographic order of vectors.

The assembly line balancing problem (ALBP) is an eminent NP-hard topic that is discussed in mass production systems with low diversity. Primarily, two types of ALBPs are discussed in the literature as type I, which aims to find the minimum number of workstations for a given cycle time, and type II, which assigns some tasks to a given number of workstations such that the maximum workstation load is minimized. To solve ALBPs, various exact, heuristic, and metaheuristic methods have been proposed. However, these methods lose their efficiency when handling large-size problems. Therefore, researchers have focused on proposing heuristic and metaheuristic algorithms to solve large-size problems, especially when they deal with real-life case problems in the industry. This study aims to present a novel and competitive exact method for solving ALBP type II based on the lexicographic order of vectors for feasible solutions. To evaluate the performance of the developed method, a group of highly used standard test problems in the literature is utilized, and the results are compared and discussed in detail. The computational results in this study specify that the developed solution approach performs efficiently and yields the best global solution of all the ALB test problems, which proves the proposed method's potential and its competitive advantage.

MDSCs Aggravate the Asthmatic Progression in Children and OVA-Allergic Mice by Regulating the Th1/Th2/Th17 Responses.

Background: Asthma is a chronic inflammatory disease of respiratory with serious risks for children. This study explored myeloid-derived suppressor cells (MDSCs) on the pathogenesis of asthmatic children and mice. Methods: The clinical study enrolled 30 asthma, 20 pneumonia, and 20 control participants. The MDSCs, Th17 and Th1 cells percentage, and IL-4, IL-12, IL-10, and IFN-γ levels were detected by flow cytometry and ELISA. In experimental asthma, mice were divided into control, ovalbumin (OVA), and OVA + MDSCs groups. The changes in inflammatory cell count and the levels of IL-5, IL-12, and IL-10 in mice BALF and the levels of inflammatory factors, IgE, and IFN-γ in mice were detected by ELISA. The amount of ROS generation and pathological changes and the levels of caspase 1 and caspase 3 were tested by flow cytometry, HE and PAS staining, and immunohistochemistry. The expression of cleaved caspase 1/caspase 1 and cleaved caspase 3/caspase 3 was detected by western blot. Results: In clinical trials, the levels of IL-12, IFN-γ, and Th1 percentage decreased in pneumonia and asthma children's peripheral blood, while the levels of IL-4 and IL-10 and the percentages MDSCs and Th17 increased. In asthma mice, pathological staining showed that asthma caused lung inflammation and damage, while the OVA + MDSC group was severer. Moreover, the percentages of eosinophils, neutrophils, lymphocytes, and the levels of inflammatory factors, IgE, ROS production, caspase 1, caspase 3, cleaved caspase 1/caspase 1, and cleaved caspase 3/caspase 3 increased in OVA + MDSC group, while the percentage of macrophages, IL-12, and IFN-γ levels reduced, illustrating that MDSCs exacerbated asthma. Conclusion: Our study indicated that MDSCs could aggravate asthma by regulating the Th1/Th2/Th17 response.