Menopause is associated with bone loss and enhanced visceral adiposity. We have shown previously that a polyclonal antibody (Ab) to the β-subunit of the pituitary hormone Fsh increases bone mass in mice. Here, we report that this Ab sharply reduces adipose tissue in wild type mice, phenocopying genetic Fshr haploinsufficiency. The Ab also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue, and enhances thermogenesis. These actions result from the specific binding of Ab to Fshβ to block its action. Our studies uncover novel opportunities for co-treating obesity and osteoporosis.

BackgroundDiarrhea is the leading infectious cause of childhood morbidity and mortality. Among bacterial agents, diarrheagenic Escherichia coli (DEC) is the major causal agent of childhood diarrhea in developing countries, particularly in children under the age of 5 years. Here, we performed a hospital-based prospective study to explore the pathotype distribution, epidemiological characteristics and antibiotic resistance patterns of DEC from < 5-year-old diarrheal children.MethodsBetween August 2015 and September 2016, 684 stool samples were collected from children (< 5 years old) with acute diarrhea. All samples were cultured and identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and biochemical tests. PCR was used for subtyping, and enteropathogenic E. coli (EPEC) isolates were identified simultaneously with serology. Furthermore, antimicrobial sensitivity tests and sequencing of antibiotic resistance-related genes were conducted.ResultsDEC strains were identified in 7.9% of the 684 stool samples. Among them, the most commonly detected pathotype was EPEC (50.0% of DEC), of which 77.8% were classified as atypical EPEC (aEPEC). Age and seasonal distribution revealed that DEC tended to infect younger children and to occur in summer/autumn periods. Multidrug-resistant DEC isolates were 66.7%; resistance rates to ampicillin, co-trimoxazole, cefazolin, cefuroxime, cefotaxime, and ciprofloxacin were ≥ 50%. Among 5 carbapenem-resistant DEC, 60.0% were positive for carbapenemase genes (2 blaNDM-1 and 1 blaKPC-2). Among 30 cephalosporin-resistant DEC, 93.3% were positive for extended-spectrum β-lactamase (ESBL) genes, with blaTEM-1 and blaCTX-M-55 being the most common types. However, no gyrA or gyrB genes were detected in 16 quinolone-resistant isolates. Notably, aEPEC, which has not received much attention before, also exhibited high rates of drug resistance (81.0%, 66.7%, and 14.3% for ampicillin, co-trimoxazole, and carbapenem resistance, respectively).ConclusionsEPEC was the most frequent DEC pathotype in acute diarrheal children, with aEPEC emerging as a dominant diarrheal agent in central China. Most DEC strains were multidrug-resistant, making even ciprofloxacin unsuitable for empiric treatment against DEC infection. Among carbapenem-resistant DEC strains, those harboring blaNDM-1 and blaKPC-2 were the main causal agents. blaTEM-1 and blaCTX-M-55 were the major genetic determinants associated with high levels of cephalosporin resistance.Electronic supplementary materialThe online version of this article (10.1186/s12879-017-2936-1) contains supplementary material, which is available to authorized users.

These results suggest that Sirt3 may be a target for amelioration of beta cell dysfunction due to obesity and T2D. Antioxid. Redox Signal. 27, 962-976.

35Menopause is associated with bone loss and visceral adiposity. Although 36 estrogen prevents bone loss, its inhibitory effect on body fat is less consistent. We 37 questioned instead whether we could target a rising Fsh level during the 38 perimenopausal transition with a single agent to increase bone mass and reduce body 39 fat. We previously showed that a polyclonal antibody (Ab) that binds to the β-subunit of 40Fsh and blocks its interaction with the Fsh receptor (Fshr) increases bone mass. Here, 41we report that the Fsh Ab causes a marked reduction in visceral white adipose tissue 42 (WAT) in mice fed a high fat diet, in ovariectomized mice, and interestingly, in mice on 43 normal chow. The global reduction in body fat, not seen in Fshr -/mice that were 44 similarly treated with Ab, was associated with profound beiging and brown adipose 45 tissue (BAT) activation, noted most impressively in the ThermoMouse, in which Luc2 is 46 driven by an Ucp1 promoter. These changes were accompanied by increased indices 47

Mutations in NPHS2, the gene that encodes podocin, are well-established causes of both familial and sporadic steroid-resistant focal segmental glomerulosclerosis (FSGS) in the pediatric population, but have not been well-characterized in late-onset disease. To investigate the role of NPHS2 polymorphisms in sporadic cases of late-onset FSGS, we studied 377 biopsy-confirmed FSGS cases and 919 controls. We identified 18 single nucleotide polymorphisms (SNPs) by resequencing a subgroup of cases and controls, and subsequently genotyped African-American and European-American cases and controls for five missense SNPs, three SNPs within introns, and four SNPs in the 3Ј untranslated region. No homozygotes or compound heterozygotes were observed for any missense mutation. R138Q carriers were more frequent among FSGS cases relative to controls (OR ϭ 4.9, P ϭ 0.06), but heterozygosity for the other four missense mutations was equally distributed among FSGS cases and controls. Finally, a common haplotype of noncoding SNPs carried by 20% of African-Americans, but not observed in EuropeanAmericans, was strongly associated with a 50% reduction in risk for sporadic FSGS (OR ϭ 0.5, P ϭ 0.001). These results indicate that genetic variation or mutation of NPHS2 may play a role in late-onset sporadic FSGS.

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The function of lymphocytes is the key to reflect the immune status of hosts. Evaluation of lymphocyte function is a useful tool to monitor the effect of immunosuppressive treatment and predict the prognosis of immune-mediated diseases (e.g., cancer, autoimmune diseases, and infectious diseases). As the lymphocytes have various activities, such as activation, cytotoxicity, and cytokine secretion, it is a challenge to evaluate the function of lymphocytes in clinical practice and the reference intervals (RIs) of lymphocyte function are rarely reported. The present study showed that the secretion of IFN-γ was well correlated with the activation, chemotaxis, and cytotoxicity of CD4+, CD8+ T cells, and NK cells, which suggests that IFN-γ production can be used as a symbol of lymphocyte function. We therefore created a simple method to detect the function of CD4+, CD8+ T cells, and NK cells simultaneously according to IFN-γ secretion by using whole blood instead of peripheral blood mononuclear cells. We further established the RIs of lymphocyte function (CD4+ T cells: 15.31–34.98%; CD8+ T cells: 26.11–66.59%; NK cells: 39.43–70.79%) in healthy adults. This method showed good reproducibility for the evaluation of lymphocyte function. The established RIs were suitable for use in other centers based on the validation data. We also validated the RIs in individuals with different immune status, and the results showed that kidney transplant recipients and infants (0–1 year) had a decreased lymphocyte function, whereas T cells in systemic lupus erythematosus patients exhibited an opposite trend. Overall, we have successfully established the RIs of lymphocyte function in healthy adults in a simple way, which might be of important clinical value in the diagnosis, monitoring, and prognosis of immune-related diseases.

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