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Osteoporosis is a chronic metabolic disease that increases bone fragility and, leads to severe osteoporotic fractures. In recent years, the use of high-throughput omics to explore physiological and pathological biomarkers related to bone metabolism has gained popularity. In this review, we first briefly review the technical approaches of proteomics. Additionally, we summarize the relevant literature in the last decade to provide a comprehensive overview of advances in human proteomics related to osteoporosis. We describe the specific roles of various proteins related to human bone metabolism, highlighting their potential as biomarkers for risk assessment, early diagnosis and disease course monitoring in osteoporosis. Finally, we outline the main challenges currently faced by human proteomics in the field of osteoporosis and offer suggestions to address these challenges, to inspire the search for novel osteoporosis biomarkers and a foundation for their clinical translation. In conclusion, proteomics is a powerful tool for discovering osteoporosis-related biomarkers, which can not only provide risk assessment, early diagnosis and disease course monitoring, but also reveal the underlying mechanisms of disease and provide key information for personalized treatment. The translational potential of this article: This review provides an insightful summary of recent human-based studies on osteoporosis-associated proteomics, which can aid the search for novel osteoporosis biomarkers based on human proteomics and the clinical translation of research results.

The expanded lethal (2) essential for life [l(2)efl] gene family is responsive to proteostatic stresses. Their protein products are core components of the stress response mechanism and are emerging as promising biomarkers for cellular stress in Apis mellifera. However, l(2)efl (LOC410857) uniquely remains unresponsive to heat stress within this gene family, and research examining its role in adaptation to other types of stress across diverse bee species is scarce. To address this knowledge gap, we cloned the l(2)efl gene from Apis cerana cerana [Accl(2)efl] and conducted a bioinformatics analysis on the encoded protein, aiming to elucidate the potential functions of Accl(2)efl. Our study encompassed assessing the role of Accl(2)efl in the response of bees to various stressful environments and its involvement in tolerance to heavy metals (Cd and Hg). Furthermore, we employed the RNAi technology to delve into the response mechanisms of Accl(2)efl under Cd and Hg stress. Our findings revealed that Accl(2)efl was activated when exposed to CdCl2 or HgCl2. Following the knockdown of Accl(2)efl, we observed that genes, such as defensins, were upregulated through the activation of the Toll signaling pathway. Conversely, the peroxisome signaling pathway was inhibited, resulting in a notable decrease in antioxidant enzyme activity. This led to a substantial elevation in Cd and Hg concentrations within hemolymph, accompanied by an increased mortality rate among bees re-exposed to CdCl2 or HgCl2. Combined, our data indicated that Accl(2)efl may plays a role in the tolerance of Apis cerana cerana to Cd/Hg stress. These findings provide a scientific basis for the further exploration of the role of Accl(2)efl in the response of bees to Cd/Hg stress and for enhancing the anti-Cd/Hg stress signaling network. They further lay a theoretical foundation for identifying new stress biomarkers for bees as well as indicators for the detection of environmental pollution.

Objective: This study aims to investigate the status of fertility preservation (FP) in young breast cancer patients. Materials and methods: A clinical database of six women with breast cancer who wished to undergo FP before starting chemotherapy were analyzed between January 2018 and December 2019 in our hospital. Among the six women, three were unmarried and three were married. Results: Three patients chose oocyte preservation and obtained 23, 7, and 17 MII oocytes, respectively. One patient chose embryo freezing, and three embryos were frozen. Fertility preservation failed for two patients, one of whom had premature ovulation, while the other patient abandoned egg retrieval on the human chorionic gonadotropin (HCG) day. Conclusion: The present results indicate that oocyte and embryo cryopreservation are effective optional methods for young breast cancer patients. However, a lack of knowledge, the urgency of cancer treatment, and financial constraints are causes for a low access rate regarding this process.

Gastric cancer (GC) is a globally important disease. Targeted therapies licensed to treat gastric cancer include trastuzumab, which targets HER2, and nivolumab or pembrolizumab, which block PD-1/PD-L1. The main challenge of tumor molecule-targeted drugs is resistance. Based on the multicomponent and multitarget characteristics of Traditional Chinese Medicine (TCM) and our previous research on Guiqi Baizhu Prescription (GQBZP) in targeting HER2/PD-L1, we used different cell models to verify the effect of quercetin targeting of HER2 and formononetin targeting of PD-L1. The results show that quercetin can inhibit MKN-45 cell proliferation by targeting HER2 to inhibit the PI3K-AKT pathway, and formononetin can regulate T-cell function by inhibiting the PD-1/PD-L1 pathway. We also used GC MKN-45 cells in a T lymphocyte co-culture model to show that quercetin and formononetin co-treatment can regulate T cell function and inhibit MKN-45 cell proliferation. More importantly, quercetin with formononetin treatment had a greater effect than treatment with either quercetin or formononetin alone. We believe that quercetin and formononetin may be useful to target HER2 and inhibit PD-1/PD-L1 in GC.

Structural health monitoring is important to ensuring the health and safety of dams. An inverse analysis method based on a novel hybrid fireworks algorithm (FWA) and the radial basis function (RBF) model is proposed to diagnose the health condition of concrete dams. The damage of concrete dams is diagnosed by identifying the elastic modulus of materials using the displacement changes at different reservoir water levels. FWA is a global optimization intelligent algorithm. The proposed hybrid algorithm combines the FWA with the pattern search algorithm, which has a high capability for local optimization. Examples of benchmark functions and pseudo-experiment examples of concrete dams illustrate that the hybrid FWA improves the convergence speed and robustness of the original algorithm. To address the time consumption problem, an RBF-based surrogate model was established to replace part of the finite element method in inverse analysis. Numerical examples of concrete dams illustrate that the use of an RBF-based surrogate model significantly reduces the computation time of inverse analysis with little influence on identification accuracy. The presented hybrid FWA combined with the RBF network can quickly and accurately determine the elastic modulus of materials, and then determine the health status of the concrete dam. Keywords: Fireworks algorithm(FWA), Radial basis function (RBF) network, Surrogate model, Inverse analysis, Structural health monitoring

Background: Manganese (Mn) and iron (Fe) are essential trace elements for humans, yet excessive exposure to Mn or Fe can accumulate in the central nervous system (CNS) and cause neurotoxicity. The purpose of this study was to investigate the effects of Mn and Fe exposure, alone or in combination, on inducing oxidative stress-induced neurological damage in rat cortical and SH-SY5Y cells, and to determine whether combined exposure to these metals increases their individual toxicity. Methods: SH-SY5Y cells and male Sprague-Dawley rats were used to observe the effects of oxidative stress-induced neurological damage induced by exposure to manganese and iron alone or in combination. To detect the expression of anti-oxidative stress-related proteins, Nrf2, HO-1, and NQO1, and the apoptosis-related proteins, Bcl2 and Bax, and the neurological damage-related protein, α-syn. To detect reactive oxygen species generation and apoptosis. To detect the expression of the rat cortical protein Nrf2. To detect the production of proinflammatory cytokines. Results: We demonstrate that juvenile developmental exposure to Mn and Fe and their combination impairs cognitive performance in rats by inducing oxidative stress causing neurodegeneration in the cortex. Mn, Fe, and their combined exposure increased the expression of ROS, Bcl2, Bax, and α-syn, activated the inflammatory factors IL-6 and IL-12, inhibited the activities of SOD and GSH, and induced oxidative stress-induced neurodegeneration both in rats and SH-SY5Y cells. Combined Mn-Fe exposure attenuated the oxidative stress induced by Mn and Fe exposure alone by increasing the expression of antioxidant factors Nrf2, HO-1, and NQO1. Conclusion: In both in vivo and in vitro studies, manganese and iron alone or in combination induced oxidative stress, leading to neuronal damage. In contrast, combined exposure to manganese and iron mitigated the oxidative stress induced by exposure to manganese and iron alone by increasing the expression of antioxidant factors. Therefore, studies to elucidate the main causes of toxicity and establish the molecular mechanisms of toxicity should help to develop more effective therapeutic modalities in the future.

Lung adenocarcinoma is a malignancy with a low overall survival and a poor prognosis. Studies have shown that lung adenocarcinoma progression relates to locus-specific/global changes in histone modifications. To explore the relationship between histone modification and gene expression changes, we focused on 11 histone modifications and quantitatively analyzed their influences on gene expression. We found that, among the studied histone modifications, H3K79me2 displayed the greatest impact on gene expression regulation. Based on the Shannon entropy, 867 genes with differential H3K79me2 levels during tumorigenesis were identified. Enrichment analyses showed that these genes were involved in 16 common cancer pathways and 11 tumors and were target-regulated by trans-regulatory elements, such as Tp53 and WT1. Then, an open-source computational framework was presented (https://github.com/zlq-imu/Identification-of-potential-LUND-driver-genes). Twelve potential driver genes were extracted from the genes with differential H3K79me2 levels during tumorigenesis. The expression levels of these potential driver genes were significantly increased/decreased in tumor cells, as assayed by RT–qPCR. A risk score model comprising these driver genes was further constructed, and this model was strongly negatively associated with the overall survival of patients in different datasets. The proportional hazards assumption and outlier test indicated that this model could robustly distinguish patients with different survival rates. Immune analyses and responses to immunotherapeutic and chemotherapeutic agents showed that patients in the high and low-risk groups may have distinct tendencies for clinical selection. Finally, the regions with clear H3K79me2 signal changes on these driver genes were accurately identified. Our research may offer potential molecular biomarkers for lung adenocarcinoma treatment.

In order to precisely assess gene expression level, a suitable internal reference gene must be chosen to quantify real-time reverse transcription polymerase chain reaction (RT-qPCR) data. For greenbug, Schizaphis graminum, a suitable reference gene for assessing the level of transcriptional expression of target genes has yet to be explored. In our study, eight reference genes, elongation fator 1 beta (Ef1β), TATA box binding protein (TBP), alpha-tubulin (α-TUB), 18S ribosomal (18S), 28S ribosomal (28S), glyceraldehyde-3-phosphate (GAPDH), actin (ACT), and ribosomal protein L18 (RPL18) were evaluated in S. graminum at different developmental stages, tissues, and insecticide treatments. To further explore whether these genes are suitable to serve as internal control, three software-based approaches (geNorm, BestKeeper, and NormFinder), ΔCt method, and one web-based comprehensive tool (RefFinder) were employed to analyze and rank the tested genes. The optimal number of reference genes was determined using the geNorm program, and the suitability of particular reference genes was empirically validated according to normalized gene expression data of three target genes, heat shock protein gene (HSP70), cytocrome P450 gene (SgraCYP18A1), and glutathione S-transferase (GST). We found that the most suitable reference genes varied considerably under different experimental conditions. For developmental stages, α-TUB and 28S were the optimal reference genes; for different tissues, 18S and ACT were suitable reference genes; for insecticide treatments, 28S and α-TUB were suitable for normalizations of expression data. In addition, 28S and α-TUB were the suitable reference gene as they had the most stable expression among different developmental stages, tissues and insecticide treatments. This should be useful for the selection of the suitable reference genes to obtain reliable RT-qPCR data in the gene expression of S. graminum.

Objective: Defects in L-selectin ligand (LSL) expression have been reported to cause implantation failure, but little is known about LSL expression in adenomyosis. This study evaluates LSL expression throughout the menstrual cycle in women with adenomyosis. Materials and methods: Endometrial samples were obtained from reproductive-aged women with adenomyosis who underwent hysterectomy. A total of 42 endometrial biopsies were included. There were 12 women in proliferative phase, 10 in early-secretory phase, 9 in mid-secretory phase, and 11 in late-secretory phase. Immunohistochemistry, western blotting, and RT-PCR were performed to evaluate LSL expression. A non-parametric Kruskal–Wallis one-way analysis of variance with multiple comparisons was performed to examine differences among menstrual phases. Results: Immunohistochemistry analysis with MECA-79 shows that LSL is expressed with weak intensity in the endometrium in all phases. In the luminal epithelium, MECA-79 reactivity increased from the proliferative to the late-secretory phase but decreased in the mid-secretory phase. There were significant differences in the mean histological scores (HSCOREs) among the proliferative, early-secretory, and late-secretory phases (p