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Background: Postmenopausal osteoporosis (PMOP) is a serious condition that affects elderly individuals. Our previous study revealed that Yigu decoction (YGD) effectively improved bone mineral density (BMD) in elderly individuals, but the mechanism underlying this effect remains unclear. In this study, we investigated the relationships among YGD, microRNAs (miRNAs), and bone metabolism by assessing the effects of YGD on the miRNA levels in patient plasma to provide a scientific basis for treating PMOP with YGD. Methods: In this clinical trial, 60 patients were randomly assigned to the YGD group or the control group (ratio of 1:1) and treated for 3 months. The primary outcome measure was BMD, and the secondary outcome measures included plasma miRNA levels, visual analogue scale (VAS) scores, alkaline phosphatase (ALP) levels, anti-tartrate acid phosphatase (TRACP-5b) levels and traditional Chinese medicine (TCM) syndrome scores. We assessed the regulatory roles of miRNAs in PMOP patients by analysing publicly available data from the Gene Expression Omnibus (GEO) database. Bioinformatics methods were also used to explore the mechanism by which YGD regulates miRNAs that are involved in bone metabolism. Results: Compared with those before treatment, the BMD, ALP levels, TRACP-5b levels, TCM syndrome scores and VAS scores improved in both groups after 3 months of treatment (P < 0.05). A total of 82 miRNAs differed between the groups. After analysing data from the GEO database, we confirmed that miR-133a-3p is the key molecule that mediates the effects of YGD intervention on PMOP. GO analysis of key genes suggested that gene enrichment was more pronounced in response to hormones, cellular response to growth factor stimulation, and positive regulation of physiological and metabolic processes. KEGG analysis revealed that these genes were enriched mainly in the PI3K-Akt, FOXO, and JAK-STAT pathways and other pathways. The results of the protein‒protein interaction (PPI) network analysis revealed that epidermal growth factor receptor (EGFR), Insulin-like growth factor 1 (IGF-1), Caveolin-1 (Cav-1) and others were core proteins. Conclusion: This study demonstrated that YGD is beneficial in the treatment of PMOP, ameliorating clinical symptoms and bone turnover indices. Moreover, the inhibition of miR-133a-3p expression may be the key mechanisms by which YGD regulates bone metabolism in the treatment of PMOP, although YGD regulates bone metabolism in a multitarget and multipathway manner. [ABSTRACT FROM AUTHOR]

Prior research has suggested an inverse correlation between dried fruit intake and type 2 diabetes mellitus (T2DM), yet the causal link remains uncertain. This study seeks to investigate the potential causal impact of dried fruit intake on T2DM, covering cases both with and without various complications, as well as glycaemic traits, using a two-sample Mendelian randomisation (MR) approach. Using MR analysis with genome-wide association study summary statistics, the primary analysis investigated the causal relationship between dried fruit intake and T2DM, both with and without complications, as well as glycaemic traits, employing the inverse variance weighted method. Supplementary analyses were conducted using MR-Egger and the weighted median method. Heterogeneity and intercept tests were utilised to evaluate the robustness of the study outcomes. The results show a significant association between dried fruit intake and T2DM without complications, as well as fasting insulin. Sensitivity analyses confirmed the robustness of the results and the independence from multicollinearity. However, no association was found between dried fruit intake and T2DM with various complications or other glycaemic traits. The significant association between dried fruit intake and T2DM without complications and fasting insulin persisted even after adjusting for BMI. This study offers genetic evidence endorsing the protective effects of dried fruit intake against T2DM, specifically for cases without complications, and in regulating fasting insulin. These findings suggest that dried fruit intake might serve as a primary preventive strategy for T2DM. [ABSTRACT FROM AUTHOR]

[Objectives] The aim of a ship's land target is to provide a judgment basis for the actual penetration and damage ability of anti-ship warheads on the warship structure. At present, the penetration capability of anti-ship missiles is calibrated by its penetration of steel plates with different thicknesses. [Methods] In this paper, the damage mode of an anti-ship missile penetrating a typical ship deck structure is studied via numerical simulation. The damage mode and motion law of the plate differ from those of the previous thick target. Based on the movement of the ship's plate frame and the actual failure mode of the ballistic missile based on the ship's land target, a multiple land-based ship structure design scheme is proposed which takes the material characteristics, dynamic boundary conditions and objective conditions into consideration. [Results] Through the numerical prediction of the designed land target, the damage pattern of the target and the motion law of the missile are similar to those of the actual situation. [Conclusions] Land targets can respond to the actual strike ability and damage effect of missiles on surface ships.

Introduction: Major depressive disorder (MDD) affects about 17% population in the world. Although abnormal energy metabolism plays an important role in the pathophysiology of MDD, however, how deficiency of adenosine triphosphate (ATP) products affects emotional circuit and what regulates ATP synthesis are still need to be elaborated. Aims: Our study aimed to investigate how deficiency of PGAM5‐mediated depressive behavior. Results: We firstly discovered that PGAM5 knockout (PGAM5−/−) mice generated depressive‐like behaviors. The phenotype was reinforced by the observation that chronic unexpected mild stress (CUMS)‐induced depressive mice exhibited lowered expression of PGAM5 in prefrontal cortex (PFC), hippocampus (HIP), and striatum. Next, we found, with the using of functional magnetic resonance imaging (fMRI), that the functional connectivity between PFC reward system and the PFC volume were reduced in PGAM5−/− mice. PGAM5 ablation resulted in the loss of dendritic spines and lowered density of PSD95 in PFC, but not in HIP. Finally, we found that PGAM5 ablation led to lowered ATP concentration in PFC, but not in HIP. Coimmunoprecipitation study showed that PGAM5 directly interacted with the ATP F1F0 synthase without influencing the interaction between ATP F1F0 synthase and Bcl‐xl. We then conducted ATP administration to PGAM5−/− mice and found that ATP could rescue the behavioral and neuronal phenotypes of PGAM5−/− mice. Conclusions: Our findings provide convincing evidence that PGAM5 ablation generates depressive‐like behaviors via restricting neuronal ATP production so as to impair the number of neuronal spines in PFC. [ABSTRACT FROM AUTHOR]

Background: Yigu decoction (YGD) is a traditional Chinese medicine prescription for the treatment of osteoporosis, although many clinical studies have confirmed its anti-OP effect, but the specific mechanism is still not completely clear., Methods: In this study, through the methods of network pharmacology and molecular docking, the material basis and action target of YGD in preventing and treating OP were analyzed, and the potential target and mechanism of YGD in preventing and treating OP were clarified by TMT quantitative protein and experiment., Results: Network pharmacology and molecular docking revealed that the active components of YGD were mainly stigmasterol and flavonoids. Molecular docking mainly studied the strong binding ability of stigmasterol to the target. Animal proteomics verified the related mechanism of YGD in preventing and treating OP. Based on the KEGG enrichment of network pharmacology and histology, our animal experiments in vivo verified that YGD may play a role in the treatment of OP by mediating hif1- α/vegf/glut1 signal pathway., Conclusions: YGD prevention and treatment of OP may be achieved by interfering with multiple targets. This study confirmed that it may promote osteoblast proliferation and protect osteoblast function by up-regulating the expression of proteins related to HIF signal pathway.