High-temperature exposure is detrimental to women's reproductive health; however, the impact caused by long-term high temperature is not comprehensive, and a stable model of estrous cycle disorder induced by a high temperature is yet lacking. Herein, we aimed to establish a stable and effective model of estrous cycle disorder in female rats induced by long-term heat stress to study its physiological and pathological characteristics and explore the underlying mechanism. In the present study, female Sprague-Dawley rats with normal estrous cycles were exposed to the temperature of 38 ± 0.5°C, relative humidity (RH) of 55 ± 5% (2 h/d, 1 time/d) hot cabin at more than 90 days. Consequently, after long-term heat stress, no difference was detected in body weight and rectal temperature, but the estrus cycle was prolonged, the uterine organ index was increased, pathological changes occurred, the increase latitude of stress hormones heat shock protein 70 (Hsp70) and corticosterone (CORT) decreased, estradiol (E2) and luteinizing hormone (LH) levels decreased, follicle stimulating hormone (FSH) and prolactin (Prl) levels increased, gonadotropin-releasing hormone (GnRH) and thyroid hormone (T4) showed no difference, and insulin (INS) decreased significantly. Moreover, the mRNA expression of the sex hormone receptor in the uterus and ovary was altered. Therefore, the estrous cycle disorder in female rats can be induced by regular heat stress for 90 days, which can be considered the pioneer method. Subsequently, prominent physiological and pathological characteristics and disruption in the hypothalamic-pituitary-gonadal (HPG) axis were noted.

Clear cell renal cell carcinoma (ccRCC) is a very common cancer in urology. Many evidences suggest that complex changed pathways take a nonnegligible part in the occurrence and development of ccRCC. Nevertheless, the underlying mechanism is not clear. In this study, the expression data between ccRCC and normal tissue samples in TCGA database were compared to distinguish differentially expressed genes (DEGs: mRNAs, miRNAs, and lncRNAs). Afterwards, we used GO enrichment and KEGG pathway enrichment analyses to explore the functions of these DEGs. We also found the correlation between three RNAs and created a competing endogenous RNA (ceRNA) network. Moreover, we used univariate Cox regression analysis to select DEGs that are connected with overall survival (OS) of ccRCC patients. We found 1652 mRNAs, 1534 lncRNAs, and 173 miRNAs that were distinguished in ccRCC compared with normal tissues. According to GO analysis, the maladjusted mRNAs are mainly concentrated in immune cell activation and kidney development, while according to KEGG, they are mainly concentrated in pathways related to cancer. A total of 5 mRNAs, 1 miRNA, and 4 lncRNAs were connected with patients' OS. In this article, a network of lncRNA-miRNA-mRNA was established; it is expected to be able to indicate possible molecular mechanisms for initial of ccRCC and provide a new viewpoint for diagnosis of ccRCC.

Hydroxytyrosol (HT) processes multiaspect pharmacological properties such as antithrombosis and antidiabetes. The aim of this study was to explore the antistherosclerotic roles and relevant mechanisms of HT.

The study is aimed at investigating the role of Nei endonuclease VIII-like1 (NEIL1) in the pathogenesis of colorectal cancer (CRC). The human CRC (HCT116 and SW480) cells were subjected to the siRNA silencing and recombinant plasmid overexpression of NEIL1. Transfection of siNEIL1 significantly inhibited the cell growth. It also increased the Bax expression levels, while it decreased the Bcl-2 expression levels in human CRC cells, leading the Bax/Bcl-2 balance toward apoptosis. Moreover, the apoptosis was promoted through the caspase-9 signaling pathway. One the other hand, high expression of NEIL1 promoted the cell viability and reduced the apoptosis, inducing the balance of Bax/Bcl-2 in the human colon cancer cells to be antiapoptotic. In addition, the caspase-9 signaling pathway inhibited apoptosis, contrary to the results obtained by downregulating NEIL1 expression. Furthermore, NEIL1 was negatively regulated by miR-7-5p, indicating that miR-7-5p inhibited the NEIL1 expression after transcription. Overexpression of miR-7-5p reversed the effects of NEIL1 on these CRC cells. In conclusion, NEIL1 promotes the proliferation of CRC cells, which is regulated negatively by miR-7-5p. These findings suggest that NEIL1 is a potential therapeutic target for CRC.

p2 of rice stripe virus may translocate from the nucleus to the cytoplasm and recruit nucleolar functions to promote virus systemic movement. Cajal bodies (CBs) are nuclear components associated with the nucleolus, which play a major role in plant virus infection. Coilin, a marker protein of CBs, is essential for CB formation and function. Coilin contains three domains, the N-terminal, the center, and the C-terminal fragments. Using yeast two-hybrid, colocalization, and bimolecular fluorescence complementation (BiFC) approaches, we show that p2 interacts with the full-length of Arabidopsis thaliana coilin (Atcoilin), the center and C-terminal domain of Atcoilin in the nucleus. Moreover, the N-terminal is indispensable for Atcoilin to interact with Cajal bodies.

Lonicera japonica is a traditional Chinese herbal medicine with antioxidation, anti-inflammatory, antibacterial, and immunoregulation functions. A method to isolate polysaccharides from Lonicera japonica (LJP) has been reported previously by our group. We also reported previously that LJP was consisted of 6 types of monosaccharides and had the characteristic absorption of typical polysaccharides. In this study, we investigated the protective effect of LJP on cardiomyocytes of mice injured by hydrogen peroxide (H2O2). The results showed that LJP can increase the cardiomyocyte viability and the activities of the enzyme (SOD, CAT, GSH-Px, AST, CPK, and LDH) in cardiomyocytes of mice injured by hydrogen peroxide. The results of intracellular ROS contents showed that a high dose (40 μg mL-1) of LJP had the best effects on protecting the cardiomyocytes of mice injured by H2O2. In addition, the measurement results of the cardiomyocyte apoptosis and the activity of caspase-3, caspase-8, and caspase-9 in cardiomyocytes confirmed this conclusion from another perspective.

Acne is the eighth most common disease worldwide. Disease burden of acne such as anxiety, reduced self-esteem, and facial scarring lowers the life quality of acne patients. Isotretinoin is the most potent treatment for moderate-severe acne. However, the adverse events of isotretinoin especially teratogenicity limit its use. This study aims at investigating the therapeutical mechanisms of isotretinoin using bioinformatics analysis. Differentially expressed genes (DEGs) were filtered from microarray datasets GSE10432, GSE10433, and GSE11792. Functional and pathway enrichment analyses of DEGs were performed. Protein-protein interaction (PPI) network and module analyses were also conducted based on DEGs. Using isotretinoin for 1 week, LCN2, PTGES, and GDF15 were upregulated and might mediate sebocytes apoptosis and thus decreased sebum production; CCL2 originated from activated TNF signaling pathway and S100A7 could be related with "acne-flare". While treating with isotretinoin for 8 weeks, key genes were downregulated, including HMGCS1, HMGCR, FDFT1, MVD, IDI1, and FDPS, which may be associated with decreased sebum synthesis; HMGCS1, HMGCR, and FDFT1 also probably associated with apoptosis of sebocytes. There were only two common genes including ACSBG1 and BCAT2 which worked in both 1 week and 8 weeks and could associate with decreased sebum synthesis and apoptosis of sebocytes, respectively. These results indicate potential therapeutics and side effect mechanisms of isotretinoin in the acne treatment and provide a research direction to further investigate the therapeutic mechanism of isotretinoin and thus develop retinoid-like compounds with similar curative effect and without teratogenicity.

With the development of three-dimensional printing (3DP) technology, the patient-specific instrumentation (PSI) has been widely applied in total knee arthroplasty (TKA). The purpose of this study was to compare the gait parameters of patients with 3DP personalized guide-assisted and standard TKA.

Rheum species present a significant economic value. Traditional Chinese medicine rhubarb is an important medicinal material in China. It has a long history of use, with a record of use as early as two thousand years ago. Here, we determined the complete chloroplast genome sequences of Rheum nobile and Rheum acuminatum and comprehensively compared them to two other available Rheum cp genomes at the genome scale. The results revealed cp genomes ranging in size from 159,051 to 161,707 bp with a similar typical quadripartite and circular structure. The genome organization, gene numbers, gene order, and GC contents of these four Rheum cp genomes were similar to those of many angiosperm cp genomes. Repeats and microsatellites were detected in the R. nobile and R. acuminatum cp genomes. The Mauve alignment revealed that there were no rearrangements in the cp genomes of the four Rheum species. Thirteen mutational hotspots for genome divergence were identified, which could be utilized as potential markers for phylogenetic studies and the identification of Rheum species. The phylogenetic relationships of the four species showed that the members of Rheum cluster into a single clade, indicating their close relationships. Our study provides valuable information for the taxonomic, phylogenetic, and evolutionary analysis of Rheum.

Diabetic nephropathy (DN) is the leading cause of ESRD. Emerging evidence indicated that proteinuria may not be the determinant of renal survival in DN. The aim of the current study was to provide molecular signatures apart from proteinuria in DN by an integrative bioinformatics approach.

Gastric cancer is a disease characterized by inflammation, and epithelial-to-mesenchymal transition (EMT) and tumor-associated macrophages (TAMs) both play a vital role in epithelial-driven malignancy. In the present study, we performed an integrated bioinformatics analysis of transcriptome data from multiple databases of gastric cancer patients and worked on a biomarker for evaluating tumor prognosis. We found that cadherin 11 (CDH11) is highly expressed not only in gastric cancer tissues but also in EMT molecular subtypes and metastatic patients. Also, we obtained evidence that CDH11 has a significant correlation with infiltrating immune cells in the tumor microenvironment (TME). Our findings reflected that CDH11 likely plays an important role in tumor immune escape and could provide a prognostic biomarker and potential therapeutic target for patients with gastric cancer.

Chemical fertilizers were applied on perennial tree vines to obtain high yields, which have resulted in considerable deterioration of soil quality, and it is likely to have negative impacts on the development of the grape industry. In this study, P. putida Rs-198 liquid biofertilizer (Rs198LBF) was inoculated into grape rhizosphere soils to assess its influence on grape growth and microbial community. Field experiment results showed that grape growth and quality increased depending on the concentrations of Rs198LBF applications. The berry weight, length, and width in addition with 60 ml Rs198LBF (1.44 × 1013 cfu ml-1 Rs-198) per grapevine treatment (BFP3) were 17.2%, 6.2%, and 4.4% higher than those of CK (control, non-inoculation) treatment, respectively. The available phosphorus contents in addition with 40 ml Rs198LBF per grapevine (BFP2) and BFP3 treatments were 12.6% and 55.3% higher than those of CK treatment (P < 0.05). The activities of invertase and alkaline phosphatase were improved in BFP2 and BFP3 treatment compared with those in CK. The relative abundance of potentially beneficial bacteria significantly increased compared with that in CK treatment (P < 0.05). The clusters of orthologous groups (COG) annotation illustrated that the application of 60 ml Rs198LBF increased the relative abundance of metabolic genes in rhizosphere soil. The results of this study show that biofertilizer is very effective in enhancing plant growth and affects soil community diversity.

This project is aimed at investigating whether CircANXA2 can promote the apoptosis of myocardial cells by inhibiting miR-133 expression and thereby participate in the development of myocardial ischemia-reperfusion injury. Materials and Method. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of CircANXA2 in H9c2 cells after hypoxia/reoxygenation (H/R) treatment. Evaluation of myocardial injury markers in H9c2 cells was performed using commercial kits, including lactate dehydrogenase (LDH), malonaldehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidation (GSH-PX). MTT analysis and flow cytometry were used to detect myocardial cell proliferation and apoptosis, respectively. Western blot was used to detect the protein expression of apoptosis-related genes.

The effects of long noncoding RNAs (lncRNAs) and their related messenger RNAs (mRNAs) remain unknown in children with acquired aplastic anemia (AA). The aim of this study is to screen key lncRNAs and mRNAs and investigate their potential roles in the pathology of acquired AA in children.

Brown adipose tissue generates heat instead of storing energy. It is important in the regulation of body weight, and individual variation in adaptive thermogenesis can be attributed to variations in the amount or activity of BAT.

Diabetic kidney disease (DKD) is one of the most common complications of diabetes and the leading cause of end-stage renal disease. Here, we investigated the association of PNPLA2 gene variations with DKD susceptibility in a Chinese Han population. A total of 818 participants with type 2 diabetes were recruited in the case-control study, including 379 patients diagnosed with DKD. We observed that 2 tagSNPs, PNPLA2 rs28633403 (A>G) and rs1138714 (A>G), were associated with DKD (rs28633403: genotype, P = 0.017; allele, P = 0.015; rs1138714: genotype, P = 0.029; allele, P = 0.018). PNPLA2 rs1138693 (T>C), a missense SNP, showed no association with DKD (genotype, P = 0.966; allele, P = 0.845). Genetic model analysis revealed that minor allele G of PNPLA2 rs28633403 was a protective factor of DKD in a dominant model adjusted by confounders (AG+GG vs. AA: adjusted odds ratio (aOR), 0.619; 95% CI 0.447-0.857; P = 0.004) and in an additive model (AG vs. AA: aOR, 0.633; 95% CI 0.447-0.895; P = 0.010; GG vs. AA: aOR, 0.588; 95% CI 0.385-0.897; P = 0.014). Minor allele G of PNPLA2 rs1138714 was associated with a higher risk of DKD in a dominant model adjusted by confounders (AG+GG vs. AA: adjusted odds ratio (aOR), 1.531; 95% CI 1.134-2.067; P = 0.005) and in an additive model (AG vs. AA: aOR, 1.529; 95% CI 1.118-2.091; P = 0.008). The combined effect of PNPLA2 rs28633403 AA+rs1138714 AG or GG genotype showed an association with DKD, adjusted by confounders (aOR, 2.194; 95% CI 1.378-3.492; P = 0.001), which was considered statistically significant with a markedly increased risk of DKD after a Holm-Bonferroni correction for multiple tests (P < 0.00125). Our results suggest that PNPLA2 rs28633403 and rs1138714 are significantly associated with the risk of DKD in a Chinese Han population with type 2 diabetes.

To perform a cost-effectiveness analysis of radium-223 plus Best Supportive Care (BSC) compared to BSC in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) and without previous docetaxel treatment in Spain.

Studies have shown that improvements in glycemic control are associated with avoidance or delayed onset of diabetes complications, improvements in health-related quality of life, and reductions in diabetes-related health care costs. Clinical practice guidelines recommend maintaining a hemoglobin A1c (HbA1c) level less than 7%, but among type 2 diabetes patients using insulin, two-thirds have HbA1c above 7% and one-third have HbA1c above 9%.

To evaluate the cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole in post-menopausal women with hormone receptor positive (HR+) and human epidermal growth receptor 2 negative (HER2-) advanced breast cancer from a UK payer perspective.

Many patients with type 2 diabetes mellitus (T2DM) do not have adequate glycemic control, leading to poor patient outcomes and high healthcare costs.