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Platelets and M2 macrophages both play crucial roles in tumorigenesis, but their relationship and the prognosis value of the relative genes in bladder cancer (BLCA) remain obscure. In the present study, we found that platelets stimulated by BLCA cell lines could promote M2 macrophage polarization, and platelets were significantly associated with the infiltration of M2 macrophages in BLCA samples. Through the bioinformatic analyses, A2M, TGFB3, and MYLK, which were associated with platelets and M2 macrophages, were identified and verified in vitro and then included in the predictive model. A platelet and M2 macrophage‐related gene signature was constructed to evaluate the prognosis and immunotherapeutic sensitivity, helping to guide personalized treatment and to disclose the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Microbial necromass is a large and persistent component of soil organic carbon (SOC), especially under croplands. The effects of cropland management on microbial necromass accumulation and its contribution to SOC have been measured in individual studies but have not yet been summarized on the global scale. We conducted a meta‐analysis of 481‐paired measurements from cropland soils to examine the management effects on microbial necromass and identify the optimal conditions for its accumulation. Nitrogen fertilization increased total microbial necromass C by 12%, cover crops by 14%, no or reduced tillage (NT/RT) by 20%, manure by 21%, and straw amendment by 21%. Microbial necromass accumulation was independent of biochar addition. NT/RT and straw amendment increased fungal necromass and its contribution to SOC more than bacterial necromass. Manure increased bacterial necromass higher than fungal, leading to decreased ratio of fungal‐to‐bacterial necromass. Greater microbial necromass increases after straw amendments were common under semi‐arid and in cool climates in soils with pH <8, and were proportional to the amount of straw input. In contrast, NT/RT increased microbial necromass mainly under warm and humid climates. Manure application increased microbial necromass irrespective of soil properties and climate. Management effects were especially strong when applied during medium (3–10 years) to long (10+ years) periods to soils with larger initial SOC contents, but were absent in sandy soils. Close positive links between microbial biomass, necromass and SOC indicate the important role of stabilized microbial products for C accrual. Microbial necromass contribution to SOC increment (accumulation efficiency) under NT/RT, cover crops, manure and straw amendment ranged from 45% to 52%, which was 9%–16% larger than under N fertilization. In summary, long‐term cropland management increases SOC by enhancing microbial necromass accumulation, and optimizing microbial necromass accumulation and its contribution to SOC sequestration requires site‐specific management. [ABSTRACT FROM AUTHOR]

This study investigates the therapeutic effect and the underlying mechanisms of ergothioneine (EGT) on the testicular damage caused by varicocele (VC) in vivo, in vitro, and in silico. This preclinical study combines a series of biological experiments and network pharmacology analyses. A total of 18 Sprague Dawley (SD) male rats were randomly and averagely divided into three groups: the sham‐operated, VC model, and VC model with EGT treatment (VC + EGT) groups. The left renal vein of the VC model and the VC + EGT groups were half‐ligated for 4 weeks. Meanwhile, the VC + EGT group was intragastrically administrated with EGT (10 mg/kg). GC1 and GC2 cells were exposed to H2O2 with or without EGT treatment to re‐verify the conclusion. The structure disorder of seminiferous tubules ameliorated the apoptosis decrease in the VC rats receiving EGT. EGT can also increase the sperm quality of the VC model rats (p < 0.05). The exposure to H2O2 decreased proliferation and increased apoptosis of GC1 and GC2 cells, which was revisable by adding EGT to the plates (p < 0.05). The network pharmacology and molecular docking were conducted to explore the potential targets of EGT in VC, and HSP90AA1 was identified as the pivotal gene, which was validated by western blot, immunohistochemistry, and RT‐qPCR both in vivo and in vitro (p < 0.05). Overall, EGT attenuates the testicular injury in the VC model both in vivo and in vitro by potentially potentiating the expression of HSP90AA1. [ABSTRACT FROM AUTHOR]

The article develops an optimized control via learning from the design idea of optimized backstepping (OB) technique for the nonlinear strict feedback systems containing the unknown dynamic and control gain functions. OB technique requires to deal with the actual and virtual controls of backstepping as the optimized solutions of corresponding subsystems so that the entire backstepping control is optimized. In the work, for achieving the optimization control, reinforcement learning (RL) of critic‐actor structure is constructed in every backstepping step on the basis of the neural network approximation of the Hamilton–Jacobi–Bellman equation's solution. Since the unknown nonlinear control gain function is considered, the complexity of control algorithm is greatly increased. However, the proposed RL is with the simple training laws, it can greatly alleviate the algorithm complexity for the optimized control. Finally, the feasibility of the method is demonstrated by both theory and simulation. [ABSTRACT FROM AUTHOR]

Aims: 12(S)‐hydroxyeicosatetraenoic (12(S)‐HETE), an alternate arachidonic acid metabolite, has been recently examined in metabolic disease. However, the role of 12(S)‐HETE in diabetic kidney disease (DKD) remains unclear. We studied for the first time the relationship of serum 12(S)‐HETE and DKD and renal function parameters in a Chinese population. Materials and Methods: We recruited 275 subjects who were diagnosed with type 2 diabetes (T2DM) for more than 10 years, including 149 DKD patients and 126 T2DM patients without DKD. Serum 12(S)‐HETE was measured using the enzyme‐linked immunosorbent assay. Results: Serum 12(S)‐HETE was significantly higher in DKD patients than controls [384.69 (77.54, 1003.05) pg/ml and 17.77 (8.11, 75.13) pg/ml, respectively, p < 0.0001]. Compared to controls, 12(S)‐HETE was significantly increased in both macroalbuminuria and microalbuminuria groups (p < 0.0001). Further, the macroalbuminuria group also had a higher serum 12(S)‐HETE level compared to the microalbuminuria group (p = 0.0063). Moreover, serum 12(S)‐HETE was positively correlated with the albuminuria level (r = 0.5833, p < 0.0001), serum creatinine (r = 0.2725, p < 0.0001), and was negatively associated with the estimated glomerular filtration rate (r = −0.2085, p = 0.0005). Further, receiver operating characteristic analysis (ROC) revealed that 12(S)‐HETE had a good performance of distinguishing DKD from controls (AUC 0.828) with a sensitivity of 0.913 and a specificity of 0.711. Conclusion: Our findings revealed that serum 12(S)‐HETE significantly associated with DKD and disease severity, suggesting that serum 12(S)‐HETE may be used as a potential biomarker for the early diagnosis of DKD. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Previous studies have shown that glucose peak time during the oral glucose tolerance test varies in type 2 diabetes patients; however, characteristics of this heterogeneity remain unclear. This research aimed to investigate the characteristics of delayed glucose peak time in type 2 diabetes. Materials and Methods: A total of 178 participants who underwent the oral glucose tolerance test were divided into five groups according to glucose peak time. Results: A total of 25 participants with normal glucose tolerance had a glucose peak at 30 min. Among participants with type 2 diabetes, 28 had a glucose peak at 60 min, 48 at 90 min, 45 at 120 min and 32 at 150 min. With the glucose peak time delayed, glycated hemoglobin, area under the glucose curve and homeostatic model assessment of insulin resistance increased gradually (P = 0.038, P < 0.0001, P < 0.0001, respectively), and oral glucose insulin sensitivity, homeostatic model assessment of β‐cell function, insulinogenic index, modified β‐cell function index and disposition indices decreased (P < 0.0001 for all). On multinominal logistic regression, insulinogenic index (odds ratio 0.73, 95% confidence interval 0.57–0.93, P = 0.01), modified β‐cell function index (odds ratio 0.67, 95% confidence interval 0.47–0.94, P = 0.023) and oral glucose insulin sensitivity (odds ratio 0.91, 95% confidence interval 0.87–0.96, P < 0.0001) were independently correlated with delayed glucose peak time. Conclusions: Delay in glucose peak time indicated an increase in blood glucose and a decrease in insulin sensitivity and secretion. Furthermore, insulinogenic index, modified β‐cell function index and oral glucose insulin sensitivity contributed to delayed glucose peak time. The purpose of this research was to investigate the characteristics of delayed glucose peak time of type 2 diabetes. Along with the delay of glucose peak time, blood glucose increased while insulin sensitivity and secretion decreased. Insulinogenic index, modified beta‐cell function index, oral glucose insulin sensitivity contributed to delayed glucose peak time. [ABSTRACT FROM AUTHOR]

ABSTRACT During the mining process, repetitive stress disturbances induced by mining activities can lead to alterations in the physical properties of coal, potentially resulting in rockburst occurrences within tunnels. To investigate the propagation rule of physical field characteristics and characteristics of failure in roadway surrounding rock under multiple disturbance damage caused by dynamic load, a combined experimental and theoretical analysis is conducted to study the weakening effect of rock mass under various disturbance circumstances. A model of roadway surrounding rock loosening and failure under multiple disturbances was proposed. The degree of damage is quantified by defining the weakening coefficient Di, A “weakening variable method” is proposed to confirm the main parameters of the Holmquist‐John‐son‐Cook (HJC) model under different disturbance conditions. The reliability of these findings was validated through a microseismic event at the Tangshan coal mine's 0250 working face in 2020, followed by numerical simulation studies. The results indicate that damaged coal weakens the intensity of stress waves at the same source velocity, with the strongest effect observed at interfaces between different damage zones. Furthermore, damaged coal exhibits a stronger weakening effect on stress wave propagation speed compared to undamaged coal in non‐interface areas. The study on roadway stability reveals that severely damaged coal‐rock samples significantly weaken stress waves; however, they also exhibit lower minimum energy for dynamic failure in roadway surrounding rock, indicating that low‐stress waves cause greater damage under severe damage conditions. The study investigates the impact of coal rock mass degradation on the stability of surrounding roadways under various disturbance conditions, which holds significant implications for the timely identification of potential instability risks in damaged coal bodies, optimization of support strategies, and ensuring mining safety. [ABSTRACT FROM AUTHOR]