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Abstract Thyroid hormones(THs) are essential for the proper functioning of the ovaries, and multiple studies have shown that thyroid abnormalities, especially during adolescence and reproductive age, can lead to lifelong ovarian dysfunction. Autoimmune thyroid disease (AITD), one of the most common organ specific autoimmune diseases, is mainly mediated by cellular autoimmune reactions, and has strong inflammatory infiltration and immune active cells, including chemokines and cytokines, which are important components of ovarian aging. This suggests that autoimmune and inflammatory molecular processes may play a role in the emergence of ovarian dysfunction. The purpose of this review is to summarize recent in vivo and in vitro evidence of a complex relationship between AITD and ovarian dysfunction. AITD is closely related to the decline of ovarian function from the perspective of antibody, cytokine, oxidative stress, and genetic factors. Finally, some of the currently known treatments for AITD and hypo ovarian disease are summarized.

IntroductionMalignancy-related ascites (MRA) is a common serious complication of many advanced malignant tumors with high morbidity and mortality. The high hospital expenditures induced by unplanned readmission in patients with MRA have become an urgent issue to the public. We aimed to overall assess the unplanned early readmission rate of patients with MRA and explore the potential risk factors for such readmission.MethodsA retrospective cohort study based on 2018 Nationwide Readmissions Database was performed and patients with MRA were recruited into the analysis. The primary outcome was unplanned 30-day readmission rate and inpatient outcomes. The multivariate logistic regression analysis was performed to evaluate the potential risk factors for such early readmission.ResultsData obtained from 32,457 patients with MRA were analyzed, and of these 7,799 individuals (24.03%) were unplanned readmitted within 30-day follow-up. The mortality rate in the readmitted population was 15.15%. Patients at younger age were at a higher risk of readmission. The morbidities including hypertension (OR=1.117, 95%CI: 1.054-1.184), hyperlipemia (OR=1.075, 95%CI: 1.009-1.146) and diabetes (OR=1.118, 95%CI: 1.053-1.188), gastrointestinal malignancies and peritoneal procedure significantly increased the risk of 30-day readmission in patients with MRA.DiscussionMore than one in five patients with MRA was unplanned readmitted within 30-day follow-up. The above risk factors should be timely intervened and the corresponding medical care should be strengthened in patients with MRA to lessen the unplanned readmission and improve the readmission outcomes.

Introduction: The study aimed to determine if hepatic steatosis assessed by fatty liver index (FLI) was an independent risk factor for male low testosterone level and whether the FLI was the strongest risk factor for low testosterone level in two different age groups. Methods: Two cross-sectional studies were performed. A total of 3,443 male participants (aged 46–75) were recruited into study A (part of lONgitudinal study (REACTION)). Then a total of 267 male participants (aged 25–45) were recruited into study B. Serum total testosterone (TT) and sex hormone-binding globulin (SHBG) levels, indicators for assessing hepatic steatosis were measured. The Pearson correlation and regression analysis were performed to investigate the risk factors for low testosterone level. Results: The FLI had the strongest negative correlation with serum testosterone in the study A (r = −0.436) and B (r = −0.542). Compared with patients with a FLI lower than 30, the risk for low testosterone level increased by 3.48-fold in subjects with a FLI higher than 60 adjusted for potential risk factors in study A. In study B, the odds ratio of low testosterone level in patients with potential hepatic steatosis was 4.26 (1.57–11.60) after adjusted for age and homeostasis model assessment of insulin resistance (HOMA-IR) and 0.59 (0.14–2.60) after adjusted for age, HOMA-IR, waist circumference, body mass index, and SHBG. Conclusions: FLI was the strongest risk factor for male low testosterone level independent of insulin resistance in male populations of different ages; however, the association can be modulated by SHBG levels in the young. Significance Statement: In the study, FLI was the strongest negative risk factor for low testosterone level in the Chinese adult male population. The results suggested that hepatic steatosis assessed by the FLI was the main risk factor for male low testosterone level, independent of age, insulin resistance, smoking, and drinking status; however, the association of FLI and TT levels can be modulated by SHBG levels. Taken together these findings indicate that clinical physicians should pay more attention to the FLI index and hepatic steatosis, so that they can take advantage of them for assessing the risk of developing of low testosterone level in the male population.

Soil salinization and nutrient deficiency limit agricultural production in the Yellow River Delta region. This study investigates the green manure-forage grass rotation on soil quality and productivity. A two-year field experiment was conducted to investigate the effects of different varieties of Sesbania cannabina and ᵡTriticosecale Wittm rotations on soil properties, biological characteristics, and adaptability in coastal saline-alkali land. Four cropping rotation systems were set: Gaoyuan 2 - Lujing 2 (G2L2), Gaoyuan 2 - Lujing 5 (G2L5), Gaoyuan 1640 - Lujing 2 (G1640L2), and Gaoyuan 1640 - Lujing 5 (G1640L5). The G2L5 rotation demonstrated superior enhancement of soil quality. The soil organic matter increased by 35.8%, and the soil electric conductivity (CEC) increased by 20.2%. Compared with T. Wittm, S. cannabina had a significant positive effect on soil physical and chemical properties. S. cannabina L5 showed improved performance in mass density, fresh weight of stem, leaf and aboveground part, etc. After S. cannabina returned to the field, T. Wittm G2 had greater plant height, thousand-grain weight, and stem weight, and the yield reached 322 kg per 667 m2. In conclusion, G2L5 is the recommended planting model in saline-alkali soil. This research offers valuable insight for the efficient planting and sustainable development of coastal saline-alkali land.

Abstract Obesity is a prominent risk factor for male infertility, and a high-fat diet is an important cause of obesity. Therefore, diet control can reduce body weight and regulate blood glucose and lipids, but it remains unclear whether it can improve male fertility and its mechanism. This study explores the effects of switching from a high-fat diet (HFD) to a normal diet (ND) on the fertility potential of obese male mice and its related mechanisms. In our study, male mice were separated into three groups: normal diet group (NN), continuous high-fat diet group (HH), and return to normal diet group (HN). The reproductive potential of mice was tested through cohabitation. Enzymatic methods and ELISA assays were used to measure metabolic indicators, follicle-stimulating hormone (FSH) levels and intratesticular testosterone levels. Transmission electron microscopy and immunofluorescence with biotin tracers assessed the integrity of the blood-testis barrier (BTB). Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were inspected for the assessment of oxidative stress. The expression and localization of BTB-related proteins were detected through the immunoblot and immunofluorescence. The mice in the high-fat diet group indicated increased body weight and epididymal fat weight, elevated serum TC, HDL, LDL, and glucose, decreased serum FSH, and dramatic lipid deposition in the testicular interstitium. Analysis of fertility potential revealed that the fertility rate of female mice and the number of pups per litter in the HH group were significantly reduced. After the fat intake was controlled by switching to a normal diet, body weight and epididymal fat weight were significantly reduced, serum glucose and lipid levels were lowered, serum FSH level was elevated and the deposition of interstitial lipids in the testicles was also decreased. Most significantly, the number of offspring of male mice returning to a normal diet was significantly increased. Following further mechanistic analysis, the mice in the sustained high-fat diet group had disrupted testicular BTB integrity, elevated levels of oxidative stress, and abnormal expression of BTB-related proteins, whereas the restoration of the normal diet significantly ameliorated the above indicators in the mice. Our study confirms diet control by switching from a high-fat diet to a normal diet can effectively reduce body weight, ameliorate testicular lipotoxicity and BTB integrity in male mice, and improve fertility potential, providing an effective treatment option for obese male infertility.

AbstractObjective Systemic immune-inflammation index (SII), a novel inflammatory indicator based on platelets, neutrophils and lymphocytes, has been shown to be associated with prognostic value in several solid tumors. However, its prognostic value in nonalcoholic fatty liver disease (NAFLD) has not been reported yet. Therefore, the present study aimed to investigate the prognostic value of SII in individuals with NAFLD.Methods Data was collected from the 2005 to 2014 National Health and Nutrition Examination Survey (NHANES, https://www.cdc.gov/nchs/nhanes/index.htm), and vital status was derived from the National Death Index (NDI) up to 31 December 2015. NAFLD was diagnosed based on Hepatic Steatosis Index (HSI). Multivariate Cox regression and Kaplan–Meier survival curves were performed to measure the hazard ratios (HRs) and 95% confidence interval (CI). Our study investigated the relationship between SII and all-cause mortality by using two-part linear regression models with penalized splines, as well as Cox models with penalized splines.Results A total of 10,787 NAFLD participants (44.14% men) aged ≥20 years old were enrolled. There were 776 deaths from all causes after a mean follow-up period of 5.6 years. According to the full adjusted Cox regression analysis, the low log2-SII group (quartile 1) and the highest log2-SII group (quartile 4) were significantly associated with increased mortality from all causes (aHR =1.86; 95% CI: 1.47–2.37; p

Summary: The hypothalamus, as a vital brain region for endocrine and metabolism regulation, undergoes functional disruption during obesity.The anti-aging effect of metformin has come into focus. However, whether it has the potential to ameliorate hypothalamic aging and dysfunction in the obese state remains unclear. In this study, obese mice were utilized to investigate the effects of metformin on the hypothalamus of obese mice. According to the results, metformin treatment resulted in improved insulin sensitivity, reduced blood glucose and lipid levels, as well as attenuation of hypothalamic aging, demonstrated by decreased SA-β-gal staining and downregulation of senescence markers. Additionally, metformin decreased the expression of endoplasmic reticulum stress-related proteins in neurons and reduced the inflammatory response triggered by microglia activation. Further mechanistic analysis revealed that metformin inhibited the expression and activation of STING and NLRP3 in microglia. These results reveal a possible mechanism by which metformin ameliorates hypothalamic aging.

IntroductionAge-related decline in testosterone is associated with Leydig cell aging with impaired testosterone synthesis in aging. Obesity accelerates the age-related decline in testosterone. However, the mechanisms underlying the Leydig cell aging and the effects of obesity on Leydig cell aging remain unclear.MethodNatural aging mice and diet-induced obese mice were used to assess the process of testicular Leydig cell senescence with age or obesity. Bioinformatic analysis of the young and aged human testes was used to explore key genes related Leydig cell aging. Leydig cell-specific p38 MAPK knockout (p38LCKO) mice were used to further analyze the roles of p38 MAPK in Leydig cell aging. The levels of testosterone and steroidogenic enzymes, activity of p38 MAPK, aging status of Leydig cells, and oxidative stress and inflammation of testes or Leydig cells were detected by ELISA, immunoblotting, immunofluorescence, and senescence-associated β-galactosidase (SA-β-Gal) staining analysis, respectively.ResultThe serum testosterone level was significantly reduced in aged mice compared with young mice. In the testis of aged mice, the reduced mRNA and protein levels of LHCGR, SRB1, StAR, CYP11A1, and CYP17A1 and the elevated oxidative stress and inflammation were observed. KEGG analysis showed that MAPK pathway was changed in aged Leydig cells, and immunoblotting displayed that p38 MAPK was activated in aged Leydig cells. The intensity of SA-β-Gal staining on Leydig cells and the number of p21-postive Leydig cells in aged mice were more than those of young mice. Similar to aged mice, the testosterone-related indexes decreased, and the age-related indexes increased in the testicular Leydig cells of high fat diet (HFD) mice. Aged p38LCKO mice had higher levels of testosterone and steroidogenic enzymes than those of age-matched wild-type (WT) littermates, with reduced the intensity of SA-β-Gal staining and the expression of p21 protein.ConclusionOur study suggested that obesity was an important risk factor for Leydig cell aging. p38 MAPK was involved in Leydig cell aging induced by age and obesity. The inhibition of p38 MAPK could delay Leydig cell aging and alleviate decline in testosterone.

Abstract Background Neutrophilic inflammation in the airway is a hallmark of bronchiectasis. Neutrophil extracellular traps (NETs) have been reported to play an important role in the occurrence and development of bronchiectasis. Neutrophil side fluorescence is one of the characteristics of neutrophils that can reflect the activation of neutrophils and the formation of NETs. Objective To explore the relationship between the values of neutrophil side fluorescence (NEUT-SFL) in the peripheral blood of bronchiectasis patients, and the severity of the disease. Methods 82 patients with bronchiectasis from the Department of Respiratory and Critical Medicine, at the Third Affiliated Hospital of Southern Medical University and were scored with Bronchiectasis Severity Index (BSI) (2019–2021). The clinical data such as the value of NEUT-SFL, neutrophil count, C-reactive protein, and procalcitonin levels were collected and retrospectively analyzed. NEUT-SFL values neutrophil count from 28 healthy subjects were also used to ascertain cut-off values. Results Based on the BSI scores, patients were divided into three categories as mild (32%), moderate (29%), and severe (39%). Our results showed that the values of NEUT-SFL were higher in bronchiectasis patients compared to healthy controls. The levels of NEUT-SFL positively correlated with the high BSI scores in patients (P = 0.037, r = 0.23) and negatively correlated with the lung function in these patients (r = − 0.35, P = 0.001). The area under the ROC curve was 0.813, the best cut-off was 42.145, indicating that NEUT-SFL values > 42.145 can potentially predict the severity of bronchiectasis. Conclusions The values of NEUT-SFL in the peripheral blood can be used for predicting the severity of bronchiectasis.

Abstract On‐line partial discharge (PD) monitoring is related to the safe and stable operation of power grid. However, the measured signal is inevitably affected by noise. Among a variety of noises, white noise is the most difficult to suppress and ubiquitous. It mainly determines the Cramer–Rao lower bound that cannot be crossed by all methods. This article proposes the Prony time‐series energy spectrum method to suppress white noise in a low signal‐to‐noise ratio environment. This method is divided into two parts: First, Prony time series energy spectrum is used to detect whether there is PD signals in the measured signal. Then, based on the least square method, the PD signal is estimated with the Prony model. In data analysis, this method can suppress ‐10dB white noise, while other methods have performed poorly or even failed under the same conditions. In general, this method has excellent anti‐noise performance compared to several other algorithms.

Abstract Background Kidney cancer, especially clear cell renal cell carcinoma (ccRCC), is one of the most common cancers in the urinary system. Previous studies suggested that certain members of MUCINs could serve as independent predictors for the survival of ccRCC patients. None of them, however, is robust enough to predict prognosis accurately. Objective To analyze the correlation of MUCINs alterations and their expression levels with the prognosis of ccRCC patients and develop a prognosis‐related predictor. Methods We applied whole‐exome sequencing in samples from 22 Chinese ccRCC patients to identify genetic alterations in MUCIN genes and analyzed their genetic alterations, expression, and correlation with survival using the TCGA, GSE73731, and GSE29069 datasets. Result Genetic alternations in MUCINs were identified in 91% and 51% of ccRCC patients in our cohort and the TCGA database, respectively. No correlation with survival was found for the genetic alterations. Using unsupervised clustering analysis of gene expression, we identified two major clusters of MUCIN expression patterns. Cluster 1 was characterized by a global overexpression of MUC1, MUC12, MUC13, MUC16, and OVGP1; and cluster 2 was characterized by a global overexpression of MUC4, MUC5B, MUC6, MUC20, EMCN, and MCAM. Patients with cluster 1 expression pattern had significantly shorter overall survival time and worse clinical features, including higher tumor grades and metastasis. Meanwhile, they had a higher level of mutation counts and more infiltrated immune cells, but lower enrichment in angiogenesis signature genes. A five‐MUCINs expression signature was constructed from cluster 1, and notably, it was demonstrated to be associated with shorter overall survival. A similar worse clinical feature, lower angiogenesis but the more immune signature, was identified in samples presented with signature 1. In the validation data set GSE29069, patients with signature 1 were also associated with a trend of poor survival outcomes. Conclusion We established a five‐MUCINs expression signature as a new prognostic marker for ccRCC. The distinct tumor microenvironment feature between the two signatures may further affect ccRCC patients’ clinical management.

Based on the mechanism of luminescence resonance energy transfer (LRET) and using a special single strand DNA as the recognition element, a portable paper-based sensor for the accurate detection of total heavy rare-earth ions (mainly Gd3+, Tb3+ and Dy3+) concentration was proposed. The RNA cleaving-DNAzyme should recognize rare-earth ions to cleave RNA on DNA duplexes linking UCNPs and AuNPs, causing UCNPs and AuNPs to approach each other, inducing LRET, which attenuated the green upconversion luminescence (UCL) triggered by the 980 nm laser. UCL was captured by a charge-coupled device (CCD) image sensor and processed with the red-green-blue (RGB) image to quantitatively analyze heavy rare-earth ions in the samples. In the range of 5–50 μmol·L-1, the sensor has good sensitivity, with the limit of detection of 1.26 μmol L−1.

In recent years, the impact of lipotoxicity on male fertility has received extensive attention, especially on Sertoli cells (SCs). In SCs, energy metabolism is important as disorders of energy metabolism result in infertility eventually. However, the underlying mechanism of lipotoxicity on energy metabolism in SCs remains unknown. Advances in high-throughput metabolomics and lipidomics measurement platforms provide powerful tools to gain insights into complex biological systems. Here, we aimed to explore the potential molecular mechanisms of palmitic acid (PA) regulating energy metabolism in SCs based on metabolomics and lipidomics. The results showed that glucose metabolism-related metabolites were not significantly changed, which suggested that PA treatment had little effect on glucose metabolism and may not influence the normal energy supply from SCs to germ cells. However, fatty acid β-oxidation was inhibited according to accumulation of medium- and long-chain acylcarnitines in cells. In addition, the pool of amino acids and the levels of most individual amino acids involved in the tricarboxylic acid (TCA) cycle were not changed after PA treatment in SCs. Moreover, PA treatment of SCs significantly altered the lipidome, including significant decreases in cardiolipin and glycolipids as well as remarkable increases in ceramide and lysophospholipids, which indicated that mitochondrial function was affected and apoptosis was triggered. The increased apoptosis rate of SCs was verified by elevated protein expression levels of Cleaved Caspase-3 and Bax as well as decreased Bcl-2 protein expression level. Together, these findings indicated that PA may result in mitochondrial dysfunction and increased apoptosis by inhibiting fatty acid β-oxidation of SCs.

Summary: Mutations in ERCC2/XPD helicase, an important component of the TFIIH complex, cause distinct human genetic disorders which exhibit various pathological features. However, the molecular mechanisms underlying many symptoms remain elusive. Here, we have shown that Ercc2/Xpd deficiency in zebrafish resulted in hypoplastic digestive organs with normal bud initiation but later failed to grow. The proliferation of intestinal endothelial cells was impaired in ercc2/xpd mutants, and mitochondrial abnormalities, autophagy, and inflammation were highly induced. Further studies revealed that these abnormalities were associated with the perturbation of rRNA synthesis and nucleolar stress in a p53-independent manner. As TFIIH has only been implicated in RNA polymerase I-dependent transcription in vitro, our results provide the first evidence for the connection between Ercc2/Xpd and rRNA synthesis in an animal model that recapitulates certain key characteristics of ERCC2/XPD-related human genetic disorders, and will greatly advance our understanding of the molecular pathogenesis of these diseases.

Iodoacetic acid (IAA) is one of the most common water disinfection byproducts (DBPs). Humans and animals are widely and continuously exposed to it. Many species of water DBPs are harmful to the reproductive system of organisms. Nevertheless, the potential effects of IAA exposure on testosterone and spermatogenesis in vivo remain ambiguous. Spermatogenous cells are the site of spermatogenesis, Leydig cells are the site of testosterone synthesis, and Sertoli cells build the blood–testis barrier (BTB), providing a stable environment for the aforementioned important physiological functions in testicular tissue. Therefore, we observed the effects of IAA on spermatogenic cells, Leydig cells, and Sertoli cells in the testis. In this study, we found that oral administration of IAA (35 mg/kg body weight per day for 28 days) in male mice increased serum LH levels and reduced sperm motility, affecting average path velocity and straight line velocity of sperm. In addition, IAA promoted the expression of γH2AX, a marker for DNA double-strand breaks. Moreover, IAA downregulated the protein expression of the scavenger receptor class B type 1 (SRB1), and decreased lipid droplet transport into Leydig cells, which reduced the storage of testosterone synthesis raw materials and might cause a drop in testosterone production. Furthermore, IAA did not affect the function of BTB. Thus, our results indicated that IAA exposure affected spermatogenesis and testosterone synthesis by inducing DNA damage and reducing lipid droplet transport.

Abstract Background As the incidence of secretory osteoporosis has increased, bone loss, osteoporosis and their relationships with thyroid-stimulating hormone (TSH) have received increased attention. In this study, the role of TSH in bone metabolism and its possible underlying mechanisms were investigated. Methods We analyzed the serum levels of free triiodothyronine (FT3), free thyroxine (FT4), and TSH and the bone mineral density (BMD) levels of 114 men with normal thyroid function. In addition, osteoblasts from rat calvarial samples were treated with different doses of TSH for different lengths of time. The related gene and protein expression levels were investigated. Results A comparison of the BMD between the high-level and low-level serum TSH groups showed that the TSH serum concentration was positively correlated with BMD. TSH at concentrations of 10 mU/mL and 100 mU/mL significantly increased the mRNA levels of ALP, COI1 and Runx2 compared with those of the control (P

In this paper, the Cauchy mixture distribution is used for rigid and affine registration. The Cauchy function has a wider effective range than the general window function, so it has a greater information utilization ratio than most registration algorithms. This means that the method can quickly match point clouds without initial registration and corresponding points. On the other hand, the computational complexity of Cauchy mixture model is lower than that of widely used Gaussian mixture model. This means that the introduction of Cauchy mixture model will save computing resources. However, the log-likelihood function of the Cauchy mixture distribution is a nonlinear function that is difficult to solve. This paper proposes an optimization method for the Cauchy mixture model, and discusses the advantages of the Cauchy mixture model in rigid and affine registration. In the experiment, compared with several other algorithms, our method quickly and accurately registers point clouds.

Registering point clouds quickly and accurately has always been a challenging task. A lot of research based on Gaussian mixture model is widely used in recent years. However, few people use other models for point cloud matching. Therefore, this paper proposes a point cloud registration algorithm based on the Laplace mixture model. In this paper, sampling variance is used to replace the variance of the likelihood estimation to successfully overcome the nonlinear problem. In addition, the Laplace model has strong robustness, which is very suitable for point cloud matching of 3D laser scanning. In the experiment, compared with several other algorithms, proposed method quickly and accurately registers point clouds.

Abstract A pot experiment was used to explore the distribution of fertilizer N and agronomic effects in a paddy soil-rice (Oryza sativa L.) system. Five treatments were set: without nitrogen, straw and inhibitor (C), urea (U), urea + straw (US), urea + urease + nitrification inhibitor (UI) and urea + urease + nitrification inhibitor + straw (UIS). Soil and urea-derived microbial biomass N increased significantly in US and UIS compared with straw-free treatments at seedling and tillering, indicating that biotic process play an important role in the retention of fertilizer N with straw addition. About 10% urea-N was recovered as fixed ammonium (FA) at seedling stage, subsequently released at tillering and maturation regardless of treatments, which emphasizes the importance of FA in the retention and supply of fertilizer N in paddy soils. Compared with U, rice yield and N uptake in US decreased by 7.8% and 25.2% respectively, while inhibitors (UIS) alleviated the reduction by 16.4% and 31.6%. The current research indicated UIS is recommended as the most appropriate management strategy in paddy soils of Northeast China based on N dynamics. But the economic effect as well as the field-scale validation need to be further evaluated.

BackgroundObesity is associated with a decrease in testicular function, yet the effects and mechanisms relative to different stages of sexual development remain unclear. The aim of this study is to determine whether high-fat diet-induced obesity impairs male fertility during puberty and in adulthood, and to ascertain its underlying mechanisms. This study aims to further reveal whether restoring to a normal diet can improve impaired fertility.MethodsMale mice were divided into 6 groups: the group N and H exposed to a normal diet or high-fat diet during puberty. The group NN or NH were further maintained a normal diet or exposed to high-fat diet in adulthood, the group HH or HN were further maintained high-fat diet or switched to normal diet in adulthood. Metabolic parameters, fertility parameters, testicular function parameters, TUNEL staining and testicular function-related proteins were evaluated, respectively.ResultsThe fertility of the mice in the high-fat diet group was impaired, which validated by declines in pregnancy rates and litter weight loss. Further analysis demonstrated the increased level of oxidative stress, the increased number of spermatogenic cell apoptosis and decreased number of sperm and decreased acrosome integrity. The expression of steroidogenic acute regulatory (StAR) and spermatogenesis related proteins (WT-1) decreased. Fertility among the HN group recovered, accompanied by the recovery of metabolism, fertility and testicular function parameters, StAR and WT-1 expression.ConclusionsThe findings suggest that high-fat diet-induced obesity impairs male fertility during puberty and in adulthood. The loss of acrosome integrity, the increase of oxidative stress, the increase of cells apoptosis and the down-regulation of StAR and WT-1 may be the underlying mechanisms. Switching from high-fat diets during puberty to normal diets in adulthood can improve male fertility.

ObjectiveThis study aimed at investigating the association between testosterone levels and gut microbiota in male patients with type 2 diabetes mellitus (T2DM) and providing a new strategy to elucidate the pathological mechanism of testosterone deficiency in T2DM patients.MethodsIn an observational study including 46 T2DM male patients, the peripheral venous blood and fecal samples of all subjects were collected. The V3–V4 regions of bacterial 16S rDNA were amplified and sequenced. Alpha and beta diversities were calculated by QIIME software. The possible association between gut microbial community and clinical indicators was assessed using the Spearman correlation coefficient. The association between the relative abundance of bacteria and testosterone levels was discovered using linear regression analysis in R language.ResultsThere was no substantial difference in alpha and beta diversity. Blautia and Lachnospirales were significantly much higher in the testosterone deficiency group. Linear regression analysis showed that the abundance of Firmicutes at the phylum level and Lachnospirales at the order level were negatively correlated with testosterone level. After correcting for C-reactive protein (CRP) and homeostatic model assessment of insulin resistance (HOMA-IR), the relative abundance of Lachnospirales still had a significant negative correlation with testosterone level. Meanwhile, at the genus level, Lachnoclostridium, Blautia, and Bergeyella had a statistically significant negative association with testosterone level, respectively. Blautia was positively associated with FPG and total cholesterol level. Streptococcus was found positively associated with insulin, connecting peptide, and index of homeostatic model assessment of insulin resistance.ConclusionT2DM patients with testosterone deficiency have different gut microbiota compositions compared with T2DM patients alone. Low serum testosterone patients tend to have an increased abundance of opportunistic pathogens, which may be related to the occurrence and development of testosterone deficiency.

Adiposity is caused by an imbalance between energy intake and consumption. Promotion of the browning of white fat increases energy expenditure and could combat adiposity. Thyroid-stimulating hormone (TSH) has been confirmed to positively correlate with adiposity. However, the putative connection between TSH and white adipose browning has never been explored. In this study, we sought to assess the effect of TSH on white adipose tissue browning and energy metabolism. Subclinical hypothyroidism mice, thyroid-specific Tshr-knockout mice injected with TSH, adipocyte-specific and global Tshr-knockout micewere subjected to morphological, physiological, genetic or protein expression analyses and metabolic cages to determine the role of TSH on the browning of white adipose tissue and metabolism. 3T3-L1 and primary SVF cells were used to verify the effects and mechanism of TSH on the browning of white adipocytes. We show that increased circulation TSH level decreases energy expenditure, promotes adiposity, impairs glucose and lipid metabolism. Knockout of Tshr decreases adiposity, increases energy expenditureand markedly promotes the development of beige adipocytesin both epididymal and inguinal subcutaneous white fat via a mechanism that likely involves AMPK/PRDM16/PGC1α. Our results reveal an important role of TSH in regulating energy balance and adiposity by inhibiting the browning of white fat.

Objectives. Peripheral artery disease (PAD) in diabetic populations is a vital chronic disease all over the world due to its high morbidity and mortality. It is important to find early simple screening biomarkers and find residual risk factors that may provide a new target for prevention and treatment of PAD in diabetic patients besides traditional cardiometabolic risk factors. Methods. We performed a cross-sectional retrospective study, and a total of 1671 T2DM participants were recruited. Receiver operating characteristic analysis, stepwise logistic regression analysis, points score system, and decision curve analysis were performed to assess the risk factors for PAD. Results. The prevalence of PAD in the study was 7.18% (n=120). Compared to the participants with the lowest quartile of cystatin C (CysC), the risk of developing PAD in participants with the highest quartile of CysC increased 6.339-fold. The CysC was the superior indicators to distinguish participants with PAD from those without PAD, with an AUC of 0.716. Stepwise logistic regression analysis showed that CysC was independent risk factor for PAD besides traditional risk factors. Combined exposure to these traditional risk factors and CysC was associated with a stepwise increase in the risk of developing PAD and even increased 11.976-fold in participants with the highest quintiles of combined exposure score (CES) based on traditional risk factors and CysC compared to the participants with the lowest quintiles of CES. Conclusions. CysC was associated with PAD independent of potential risk factors in diabetic populations. The CysC was a reliable marker for the early screening of PAD in diabetic patients besides traditional cardiometabolic risk factors.

Application of nitrification inhibitors (NIs) with nitrogen (N) fertilizer is one of the most efficient ways to improve nitrogen use efficiency (NUE). To fully understand the efficiency of NIs with N fertilizer on soil nitrification, yield and NUE of maize (Zea mays L.), an outdoor pot experiment with different NIs in three soils with different pH was conducted. Five treatments were established: no fertilizer (Control); ammonium sulfate (AS); ammonium sulfate + 3, 4-dimethyl-pyrazolate phosphate (DMPP) (AD); ammonium sulfate + nitrogen protectant (N-GD) (AN); ammonium sulfate + 3, 4-dimethyl-pyrazolate phosphate + nitrogen protectant (ADN). The results showed that NIs treatments (AD, AN and ADN) significantly reduced soil nitrification in the brown and red soil, especially in AD and ADN, which decreased apparent nitrification rate by 28% - 44% (P < 0.05). All NIs treatments significantly increased yield and NUE of maize in three soils, especially ADN in the cinnamon soil and AD in the red soil were more efficiency, which significantly increased maize yield and apparent nitrogen recovery by 5.07 and 6.81 times, 4.39 and 8.16 times, respectively. No significant difference on maize yield was found in the brown soil, but AN significantly increased apparent nitrogen recovery by 70%. Given that the effect of NIs on both soil nitrification and NUE of maize, DMPP+N-GD was more efficient in the cinnamon soil, while N-GD and DMPP was the most efficiency in the brown and red soil, respectively. In addition, soil pH and soil organic matter play important role in the efficiency of NIs.

PrimPols are a class of primases that belong to the archaeo-eukaryotic primase (AEP) superfamily but have both primase and DNA polymerase activities. Replicative polymerase from NrS-1 phage (NrSPol) is a representative of the PrimPols. In this study, we identified key residues for the catalytic activity of NrSPol and found that a loop in NrSPol functionally replaces the zinc finger motif that is commonly found in other AEP family proteins. A helix bundle domain (HBD), conserved in the AEP superfamily, was recently reported to bind to the primase recognition site and to be crucial for initiation of primer synthesis. We found that NrSPol can recognize different primase recognition sites, and that the initiation site for primer synthesis is not stringent, suggesting that the HBD conformation is flexible. More importantly, we found that although the HBD-inactivating mutation impairs the primase activity of NrSPol, it significantly enhances the DNA polymerase activity, indicating that the HBD hinders the DNA polymerase activity. The conflict between the primase activity and the DNA polymerase activity in a single protein with the same catalytic domain may be one reason for why DNA polymerases are generally unable to synthesize DNA de novo.

Salt stress and nutrient deficiency strongly limited the productivity of coastal saline-alkali land in the Yellow River Delta. Biochar has been widely used to improve soil health and promote crop yield, and the positive effects of nitrification inhibitors on fertilizer use efficiency, especially nitrogen, were also verified. However, there were few types of research on the combined application of biochar and nitrification inhibitor dicyandiamide (DCD) on saline-alkali soil of the Yellow River Delta, China. In this study, five treatments, including no nitrogen (CK), normal NPK (N), NPK + 1%biochar (B), NPK + 2%DCD (D), and NPK + 1%biochar + 2%DCD (BD) were set to investigate the single and combined effect of biochar and DCD on nitrogen transform, soil properties, bacterial community structure, and soybean production. Results showed that BD application inhibited nitrification and increased the soil’s nitrate supply at the flowering stage, which reduced nitrogen waste and met the nitrogen demand for soybean growth. Biochar addition increased the soil’s pH and decreased the soil’s electrical conductivities and accelerated the soil’s macroaggregates formation, with the soil’s average mass diameter and geometric average diameter increasing by 78.69% and 30% in B, and 71.29% and 29.34% in BD relative to CK. Positive effects of inhibitors on soybean production were found in increasing soybean yield, hundred-grain weight, aboveground biomass, etc. Proteobacteria was the dominant phylum in the bacterial communities detected, and bacterial community diversity was significantly explained by nitrate content and soil aggregates (p < 0.05). Soil pH and DCD addition mainly influenced the abundance of the bacterial community, especially Actinobacteria. Biochar with DCD could be a feasible fertilization scheme for the coastal saline-alkali land in the Yellow River Delta, China.

Abstract Background α-Linolenic acid (ALA) is a plant-derived omega-3 unsaturated fatty acid that is rich in flaxseed oil (FO). The effect of FO on bone health is controversial. This study aims to evaluate the effect of FO on bone damage induced by a high-fat diet (HFD) and to explore the possible mechanism. Methods Male Sprague-Dawley rats were fed a normal control diet (NC, 10% fat), FO diet (NY, 10% fat), HFD (60% fat), or HFD containing 10% FO (HY, 60% fat) for 22 weeks. Micro CT and three-point bending tests were conducted to evaluate bone microstructure and biomechanics. Serum was collected for the detection of ALP, P1NP, and CTX-1. Rat primary osteoblasts (OBs) were treated with different concentrations of ALA with or without palmitic acid (PA) treatment. The ALP activity, osteogenic-related gene and protein expression were measured. Results Rats in the HFD group displayed decreased biomechanical properties, such as maximum load, maximum fracture load, ultimate tensile strength, stiffness, energy absorption, and elastic modulus, compared with the NC group (p

Abstract Background Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality all over the world. Acute exacerbation of COPD (AECOPD) not only accelerates the progression of disease, but also causes hospital administration and death events. Epidemiologic studies have shown air pollution is a high risk factor of AECOPD. However, there are rare technics or treatment strategies recommended to reduce severe air pollution related AECOPD. Methods This is a multi-center, prospective, randomized and standard treatment parallel control clinical trial. Seven hundred sixty-four stable COPD patients in group B, C and D according to GOLD 2017 will be recruited and equally divided into two parallel groups, salvational intervention (SI group) and control group (CT group). Original treatments for participants include tiotropium (18μg once q.d), budesonide/formoterol (160μg/4.5μg once or twice b.i.d) or budesonide/formoterol (160μg/4.5μg once or twice b.i.d) with tiotropium (18μg once q.d). The savational intervention for SI group is routine treatment plus budesonide/formoterol (160μg/4.5μg once b.i.d) from the first day after severe air pollution (air quality index, AQI ≥200) to the third day after AQI

The widely distributed “Step-type” landslides in the Three Gorges Reservoir (TGR) area have caused serious casualties and heavy economic losses. The prediction research of landslide displacement will be beneficial to the establishment of local geological hazard early warning systems for the realization of scientific disaster prevention and mitigation. However, the number of observed data like landslide displacement, rainfall, and reservoir water level in this area is very small, which results in difficulties for the training of advanced deep learning model to obtain more accurate prediction results. To solve the above problems, a Two-stage Combined Deep Learning Dynamic Prediction Model (TC-DLDPM) for predicting the typical “Step-type” landslides in the TGR area under the condition of small samples is proposed. The establishment process of this method is as follows: (1) the Dynamic Time warping (DTW) method is used to enhance the small samples of cumulative displacement data obtained by the Global Positioning System (GPS); (2) A Difference Decomposition Method (DDM) based on sequence difference is proposed, which decomposes the cumulative displacement into trend displacement and periodic displacement, and then the cubic polynomial fitting method is used to predict the trend displacement; (3) the periodic displacement component is predicted by the proposed TC-DLDPM model combined with external environmental factors such as rainfall and reservoir water level. The TC-DLDPM model combines the advantages of Convolutional Neural Network (CNN), Attention mechanism, and Long Short-term Memory network (LSTM) to carry out two-stage learning and parameter transfer, which can effectively realize the construction of a deep learning model for high-precision under the condition of small samples. A variety of advanced prediction models are compared with the TC-DLDPM model, and it is verified that the proposed method can accurately predict landslide displacement, especially in the case of drastic changes in external factors. The TC-DLDPM model can capture the spatio-temporal characteristics and dynamic evolution characteristics of landslide displacement, reduce the complexity of the model, and the number of model training calculations. Therefore, it provides a better solution and exploration idea for the prediction of landslide displacement under the condition of small samples.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder with multifactorial etiology. The role of microglia in the pathogenesis of AD has been increasingly recognized in recent years; however, the detailed mechanisms shaping microglial phenotypes in AD-relevant pathological settings remain largely unresolved. Myocyte-specific enhancer factor 2C (Mef2C) is a transcription factor with versatile functions. Recent studies have attributed aging-related microglial changes to type I interferon (IFN-I)-associated Mef2C deregulation. In view of the close relationship between brain aging and AD, it is of great interest to determine microglial Mef2C changes in AD-related conditions. In this study, we have found that suppressed Mef2C nuclear translocation was an early and prominent microglial phenotype in a mouse model of brain amyloidosis (5×FAD mice), which exacerbated with age. Echoing the early Mef2C deregulation and its association with microglial activation, transcriptional data showed elicited IFN-I response in microglia from young 5×FAD mice. Amyloid beta 42 (Aβ42) in its oligomeric forms promoted Mef2C deregulation in microglia on acute organotypic brain slices with augmented microglial activation and synapse elimination via microglial phagocytosis. Importantly, these oligomeric Aβ42-mediated microglial changes were substantially attenuated by blocking IFN-I signaling. The simplest interpretation of the results is that Mef2C, concurring with activated IFN-I signaling, constitutes early microglial changes in AD-related conditions. In addition to the potential contribution of Mef2C deregulation to the development of microglial phenotypes in AD, Mef2C suppression in microglia may serve as a potential mechanistic pathway linking brain aging and AD.

Atherosclerotic cardiovascular disease is one of the leading causes of death worldwide. Establishing animal models of atherosclerosis is of great benefit for studying its complicated pathogenesis and screening and evaluating related drugs. Although researchers have generated a variety of models for atherosclerosis study in rabbits, mice and rats, the limitations of these models make it difficult to monitor the development of atherosclerosis, and these models are unsuitable for large scale screening of potential therapeutic targets. On the contrast, zebrafish can fulfill these purposes thanks to their fecundity, rapid development ex utero, embryonic transparency, and conserved lipid metabolism process. Thus, zebrafish have become a popular alternative animal model for atherosclerosis research. In this mini review, we summarize different zebrafish models used to study atherosclerosis, focusing on the latest applications of these models to the dynamic monitoring of atherosclerosis progression, mechanistic study of therapeutic intervention and drug screening, and assessment of the impacts of other risk factors.

In this paper, a kind of node_face frictional contact FM-BEM penalty function method is presented for 3D elastic frictional contact nonlinear problems. According to the principle of minimum potential energy, nonpenetrating constraints are introduced into the elastic frictional contact system as a penalty term. By using the least square method and penalty function method, an optimization mathematical model and a mathematical programming model with a penalty factor are established for the node_face frictional contact nonlinear system. For the two models, a penalty optimization IGMRES (m) algorithm is proposed, and the influences of different penalty factors on the solution of the whole system are analyzed. Finally, a numerical simulation is carried out for two elastic frictional contact objects, and some important results including displacements, pressures, friction forces, and friction slips in the contact area are presented. Theoretical analysis and numerical experiment show that the newly presented FM-BEM penalty function method not only is efficient and practical but also has much superiority. It is easy to implement, and it is fast convergent with good stability.

The classical composite midpoint rectangle rule for computing Cauchy principal value integrals on an interval is studied. By using a piecewise constant interpolant to approximate the density function, an extended error expansion and its corresponding superconvergence results are obtained. The superconvergence phenomenon shows that the convergence rate of the midpoint rectangle rule is higher than that of the general Riemann integral when the singular point coincides with some priori known points. Finally, several numerical examples are presented to demonstrate the accuracy and effectiveness of the theoretical analysis. This research is meaningful to improve the accuracy of the collocation method for singular integrals.

Objectives. Nonalcoholic fatty liver disease (NAFLD) and hyperlipidemia (HL) are common metabolic disorders due to overnutrition and obesity. NAFLD is often associated with hyperlipidemia. The aim of this study was to identify and compare the erythrocyte membrane lipids profile in NAFLD patients with or without HL. Methods. A total of 112 subjects (with similar age and body mass index) were divided into four groups: (1) normal controls, (2) NAFLD alone, (3) HL alone, and (4) NAFLD combined with HL (NAFLD + HL). Lipid was extracted from the erythrocyte membrane, and lipid profiles of subjects were analyzed by liquid chromatography mass spectrometry (LC-MS). Results. Data sets from 103 subjects were adopted for lipidomic analysis. Significant changes of lipid species were observed in patient groups, especially in the HL group and NAFLD + HL group. The HL group showed increased level of most lipid species, and decreased level of most lipid species was observed in the NAFLD + HL group. The weight percent of myristic acid, stearic acid, erucic acid, and docosahexaenoic acid also showed distinct variation between different groups. Conclusions. NAFLD, HL, and NAFLD + HL all had an impact on lipid profiling of the erythrocyte membrane. The influence of NAFLD alone is less important compared with HL. Some lipids should be highlighted because of their specific role in cell function and systemic metabolism.

Hypothyroidism is a common disease, and its molecular mechanism still needs further investigation. Lysine succinylation is found to be involved in various metabolic processes associated with hypothyroidism. We performed quantitative analysis on lysine succinylome in thyroids of rats with hypothyroxinemia, which was induced through the administration of a high-fat diet. Overall, 129 differentially expressed proteins were quantified. Downregulated proteins were enriched in the thyroid hormone synthesis and thyroid hormone signaling pathways and were mainly localized in the mitochondria. In addition, 172 lysine succinylation sites on 104 proteins were obviously changed. Decreased succinylated proteins were involved in diverse metabolic pathways and were primarily localized in mitochondria. Finally, the mitochondrial oxygen consumption rates of human normal thyroid epithelial cells were measured to further verify the role of lysine succinylation. The mitochondrial oxygen consumption rates were markedly blunted in the cells treated with palmitic acid (all p

LIN28 is an RNA binding protein that plays crucial roles in pluripotency, glucose metabolism, tissue regeneration, and tumorigenesis. LIN28 binds to the let-7 primary and precursor microRNAs through bipartite recognition and induces degradation of let-7 precursors (pre-let-7) by promoting oligouridylation by terminal uridylyltransferases (TUTases). Here, we report that the zinc knuckle domain (ZKD) of mouse LIN28 recruits TUT4 to initiate the oligouridylation of let-7 precursors. Our crystal structure of human LIN28 in complex with a fragment of pre-let-7f-1 determined to 2.0 Å resolution shows that the interaction between ZKD and RNA is constrained to a small cavity with a high druggability score. We demonstrate that the specific interaction between ZKD and pre-let-7 is necessary and sufficient to induce oligouridylation by recruiting the N-terminal fragment of TUT4 (NTUT4) and the formation of a stable ZKD:NTUT4:pre-let-7 ternary complex is crucial for the acquired processivity of TUT4.

Our previous studies suggested that the thyroid might be a target organ affected by lipotoxicity, which might be partially related to the increasing prevalence of subclinical hypothyroidism. However, the underlying molecular mechanism is not yet clearly established. This study aimed to assess the effect of palmitic acid stimulation on thyrocyte function. Upon palmitic acid stimulation, intracellular contents of lipids, as well as the expression and activity of three key molecules in thyroid hormone synthesis (i.e., thyroglobulin, sodium iodide symporter, and thyroperoxidase), were determined in human primary thyrocytes. The contents of BODIPY® FL C16 (the fluorescently labeled palmitic acid analogue) entering into the thyrocytes were gradually increased with time extending. Accordingly, the intracellular accumulation of both triglyceride and free fatty acids increased in dose- and time-dependent manners. The effect of palmitic acid stimulation on thyroid hormone synthesis was then determined. Both the mRNA and protein levels of thyroglobulin, sodium iodide symporter, and thyroperoxidase were decreased following palmitic acid stimulation. Consistently, upon palmitic acid stimulation, the secreted thyroglobulin levels in supernatants, 131I uptake, and extracellular thyroperoxidase activity were all decreased in a dose-dependent manner. Our results demonstrated that upon palmitic acid stimulation, the expressions of the key molecules (thyroglobulin, sodium iodide symporter, and thyroperoxidase) were reduced and their activities were suppressed, which might lead to impaired thyroid hormone synthesis.

Cholesterol homeostasis is strictly regulated through the modulation of HMG-CoA reductase (HMGCR), the rate-limiting enzyme of cholesterol synthesis. Phosphorylation of HMGCR inactivates it and dephosphorylation activates it. AMP-activated protein kinase (AMPK) is the major kinase phosphorylating the enzyme. Our previous study found that thyroid-stimulating hormone (TSH) increased the hepatocytic HMGCR expression, but it was still unclear whether TSH affected hepatic HMGCR phosphorylation associated with AMPK. We used bovine TSH (bTSH) to treat the primary mouse hepatocytes and HepG2 cells with or without constitutively active (CA)-AMPK plasmid or protein kinase A inhibitor (H89), and set up the TSH receptor (Tshr)-KO mouse models. The p-HMGCR, p-AMPK, and related molecular expression were tested. The ratios of p-HMGCR/HMGCR and p-AMPK/AMPK decreased in the hepatocytes in a dose-dependent manner following bTSH stimulation. The changes above were inversed when the cells were treated with CA-AMPK plasmid or H89. In Tshr-KO mice, the ratios of liver p-HMGCR/HMGCR and p-AMPK/AMPK were increased relative to the littermate wild-type mice. Consistently, the phosphorylation of acetyl-CoA carboxylase, a downstream target molecule of AMPK, increased. All results suggested that TSH could regulate the phosphorylation of HMGCR via AMPK, which established a potential mechanism for hypercholesterolemia involved in a direct action of the TSH in the liver.

This study investigated the influence of nitrogen (N) fertilizer and straw on intact amino acid N uptake by soil microorganisms and the relationship between amino acid turnover and soil properties during the wheat growing season. A wheat pot experiment was carried out with three treatments: control (CK), N fertilizer (NF) and N fertilizer plus rice straw (NS). We used stable isotope compound-specific analysis to determine the uptake of 13C,15N-glycine by soil microorganisms. In the NF treatment, microbial 13C,15N-glycine uptake was lower compared with CK, suggesting that inorganic N was the preferred N source for soil microorganisms. However, The application of straw with N fertilizer (in NS treatment) increased microbial 13C,15N-glycine uptake even with the same amount of N fertilizer application. In this treatment, enzyme activities, soil microbial biomass C and microbial biomass N increased simultaneously because more C was available. Soil mineral N and plant N contents all decreased substantially. The increased uptake of intact 13C,15N-glycine in the NS treatment can be attributed to direct assimilation by soil microorganisms to satisfy the demand for N when inorganic N was consumed.

A field experiment was carried out to evaluate the effect of organic amendments on soil organic carbon, total nitrogen, bulk density, aggregate stability, field capacity and plant available water in a representative Chinese Mollisol. Four treatments were as follows: no fertilization (CK), application of inorganic fertilizer (NPK), combined application of inorganic fertilizer with maize straw (NPK+S) and addition of biochar with inorganic fertilizer (NPK+B). Our results showed that after three consecutive years of application, the values of soil bulk density were significantly lower in both organic amendment-treated plots than in unamended (CK and NPK) plots. Compared with NPK, NPK+B more effectively increased the contents of soil organic carbon, improved the relative proportion of soil macro-aggregates and mean weight diameter, and enhanced field capacity as well as plant available water. Organic amendments had no obvious effect on soil C/N ratio or wilting coefficient. The results of linear regression indicated that the improvement in soil water retention could be attributed to the increases in soil organic carbon and aggregate stability.

The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH) and bone mineral density (BMD) in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells.We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA) was used to detect serum FSH, luteinizing hormone (LH), and estradiol (E2). Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E2. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL), and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP) staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank), Trap, matrix metalloproteinase-9 (Mmp-9) and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction).1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner.The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro.

Our previous study found that thyroid-stimulating hormone promoted sterol regulatory element-binding protein-2 (SREBP-2) expression and suppressed AMP-activated protein kinase (AMPK) activity in the liver, but it was unclear whether there was a direct link between TSH, AMPK and SREBP-2. Here, we demonstrate that the 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR)-induced activation of AMPK directly inhibited the expression of SREBP-2 and its target genes HMGCR and HMGCS, which are key enzymes in cholesterol biosynthesis, and suppressed the TSH-stimulated up-regulation of SREBP-2 in HepG2 cells; similar results were obtained in TSH receptor knockout mice. Furthermore, AMPK, an evolutionally conserved serine/threonine kinase, phosphorylated threonine residues in the precursor and nuclear forms of SREBP-2, and TSH interacted with AMPK to influence SREBP-2 phosphorylation. These findings may represent a molecular mechanism by which AMPK ameliorates the hepatic steatosis and hypercholesterolemia associated with high TSH levels in patients with subclinical hypothyroidism (SCH).

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic triglyceride accumulation, ranging from steatosis to steatohepatitis and cirrhosis. NAFLD is a risk factor for cardiovascular diseases and is associated with metabolic syndrome. Antihyperlipidemic drugs are recommended as part of the treatment for NAFLD patients. Although fibrates activate peroxisome proliferator-activated receptor α (PPARα), leading to the reduction of serum triglyceride levels, the effects of these drugs on NAFLD remain controversial. Clinical studies have reported that PPARα activation does not improve hepatic steatosis. In the present study, we focused on exploring the effect and mechanism of PPARα activation on hepatic triglyceride accumulation and hepatic steatosis. Male C57BL/6J mice, Pparα-null mice and HepG2 cells were treated with fenofibrate, one of the most commonly used fibrate drugs. Both low and high doses of fenofibrate were administered. Hepatic steatosis was detected through oil red O staining and electron microscopy. Notably, in fenofibrate-treated mice, the serum triglyceride levels were reduced and the hepatic triglyceride content was increased in a dose-dependent manner. Oil red O staining of liver sections demonstrated that fenofibrate-fed mice accumulated abundant neutral lipids. Fenofibrate also increased the intracellular triglyceride content in HepG2 cells. The expression of sterol regulatory element-binding protein 1c (SREBP-1c) and the key genes associated with lipogenesis were increased in fenofibrate-treated mouse livers and HepG2 cells in a dose-dependent manner. However, the effect was strongly impaired in Pparα-null mice treated with fenofibrate. Fenofibrate treatment induced mature SREBP-1c expression via the direct binding of PPARα to the DR1 motif of the SREBP-1c gene. Taken together, these findings indicate the molecular mechanism by which PPARα activation increases liver triglyceride accumulation and suggest an adverse effect of fibrates on the pathogenesis of hepatic steatosis.

The Ferric uptake regulatory protein (Fur) is a transcriptional regulatory protein that functions to control gene transcription in response to iron in a number of pathogenic bacteria. In this study, we applied a label-free, quantitative and high-throughput analysis method, Interferometric Reflectance Imaging Sensor (IRIS), to rapidly characterize Fur-DNA interactions in vitro with predicted Fur binding sequences in the genome of Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea. IRIS can easily be applied to examine multiple protein-protein, protein-nucleotide and nucleotide-nucleotide complexes simultaneously and demonstrated here that seventy percent of the predicted Fur boxes in promoter regions of iron-induced genes bound to Fur in vitro with a range of affinities as observed using this microarray screening technology. Combining binding data with mRNA expression levels in a gonococcal fur mutant strain allowed us to identify five new gonococcal genes under Fur-mediated direct regulation.

Abstract Background Serum lipid profiles may be influenced by thyroid function, but the detailed mechanism remains unclear. Increasing evidence suggests that thyrotropin (TSH) may exert extra-thyroidal effects. The goal of this study was to evaluate the relationship between serum TSH levels and the lipid profiles in euthyroid non-smokers with newly diagnosed asymptomatic coronary heart disease (CHD). Methods This was a retrospective study of 406 euthyroid non-smokers (187 males and 219 females) with newly diagnosed asymptomatic CHD from 2004 to 2010 in Jinan, China. Lipid parameters and the levels of TSH, FT3, and FT4 were determined. Multiple linear regression analysis and Logistic regression analysis were used to assess the influence of TSH on the lipid profiles and the risks of dyslipidemia. Results The TSH level, even within the normal range, was positively and linearly correlated with total cholesterol (TC), non-high density lipoprotein cholesterol (non-HDL-C) and triglycerides (TG) (Beta = 0.173, 0.181 and 0.103, respectively, P < 0.01 in all). With 1 mIU/L rise of TSH, the levels of TC, TG and non-HDL-C will increase by 1.010, 1.064, and 1.062 mmol/L, respectively. The odds ratio of hypercholesterolemia and hypertriglyceridemia with respect to the serum TSH level was 1.640 (95% CI 1.199-2.243, P = 0.002) and 1.349 (95% CI 1.054-1.726, P = 0.017), respectively. Conclusions TSH levels were correlated in a positive linear manner with the TC, non-HDL-C and TG levels in euthyroid non-smokers with newly diagnosed asymptomatic CHD. TSH in the upper limits of the reference range might exert adverse effects on lipid profiles and thus representing as a risk factor for hypercholesterolemia and hypertriglyceridemia in the context of CHD.

Green manures (GM) combined with fertilizer reduction is an efficient measure to alleviate the environmental issues caused by the overapplication of chemical fertilizer. However, both the environmental and economic benefits remain unclear in coastal regions that are affected by both soil salinization and climate change. A field experiment was conducted in low-yield cropland in the Yellow River Delta to explore the effects of green manure rotation combined with fertilizer reduction on the soil environment and economic sustainability. Two GM species, Vicia villosa (HV) and Orychophragmus violaceus (OV), a traditional winter wheat (Wheat), were grown in winter, with a fallow control (Fallow). In the subsequent maize season, three fertilizer rate treatments, a full rate of 600 kg ha-1 compound fertilizer (F100), 85% of the full rate (F85), and 70% of the full rate (F70), were applied in each former treatment. The results indicated that GM return markedly increased soil total N (TN) and P (TP) before the V6 stage of maize (when maize had 6 leaves). The average TN contents of HV and OV increased by 56.9% and 38.5%, respectively, compared with that of Wheat, while the values for TP were 13.6% and 16.9%. Compared with Fallow, the maize yields of HV and OV increased by 25.6% and 13.8%, respectively, while that of Wheat decreased by 9.1%. The average partial fertilizer productivities (PFPs) for HV and OV increased by 25.3% and 14.0% compared with Fallow, while Wheat decreased by 8.9%. The PFPs for F85 and F70 increased by 19.4% and 37.7%, respectively, compared with F100. Reducing the fertilizer rate to 70% in the HV-maize rotation pattern did not reduce but increased the total net profit and rate of return. Thus, HV-maize rotation combined with 30% fertilizer reduction is suggested for sustainable agriculture in this region. [ABSTRACT FROM AUTHOR]