Cardiovascular disease (CVD) is one of the leading causes of mortality in developed countries. The incidence of CVD is sexually dimorphic, and research has focused on the contribution of sex steroids to the development and progression of the cardiometabolic syndrome, which is defined as a clustering of interrelated risk factors that promote the development of atherosclerosis (which can lead to CVD) and type 2 diabetes mellitus. Data are inconclusive as to how sex steroids and their respective receptors increase or suppress the risk of developing the cardiometabolic syndrome and thus CVD. In this Review, we discuss the potential role, or roles, of sex hormones in cardiometabolic health by first focusing on the influence of oestrogens and their receptors on the risk of developing cardiometabolic syndrome and CVD. We also highlight what is known about testosterone and its potential role in protecting against the development of the cardiometabolic syndrome and CVD. Given the inconclusive nature of the data regarding the direct effects of each sex hormone, we advocate and highlight the importance of studying the relative levels and the ratio of sex hormones to each other, as well as the use of cross sex hormone therapy and its effect on cardiometabolic health.

In this paper, we investigate a correlation between theoretical calculations and experimental data to explain the electronic structure and optical properties of silver molybdate (β-Ag 2 MoO 4 ) microcrystals synthesized by the microwave-assisted hydrothermal method. X-ray diffraction, Rietveld refinement, and micro-Raman spectroscopy confirmed that these microcrystals crystallize in a spinel-type cubic structure. Field-emission scanning electron microscopy images revealed that the processing temperatures influence in the final shape of microcrystals. Optical properties were analyzed by ultraviolet−visible diffuse reflectance spectroscopy; the increase in the optical band gap energy (E gap ) (from 3.24 to 3.31 eV) with processing temperature is associated with the reduction of intermediary energy levels. First-principles quantum mechanical calculations based on the density functional theory at the B3LYP level were conducted. The calculated band structure revealed an indirect E gap of approximately 4.00 and 3.34 eV for the β-Ag 2 MoO 4 without and with the formation of defects, respectively. Theoretical calculations based on density of states and electron density maps were employed to understand the polarization phenomenon induced by structural defects in the β-Ag 2 MoO 4 crystals. Finally, photoluminescence properties at room temperature of β-Ag 2 MoO 4 microcrystals were explained by the charge-transfer mechanism involving tetrahedral [MoO 4 ] clusters.

COVID-19 pandemic has infected more than 154 million people worldwide and caused more than 3.2 million deaths. It is transmitted by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and affects the respiratory tract as well as extra-pulmonary systems, including the pancreas, that express the virus entry receptor, Angiotensin-Converting Enzyme 2 (ACE2) receptor. Importantly, the endocrine and exocrine pancreas, the latter composed of ductal and acinar cells, express high levels of ACE2, which correlates to impaired functionality characterized as acute pancreatitis observed in some cases presenting with COVID-19. Since acute pancreatitis is already one of the most frequent gastrointestinal causes of hospitalization in the U.S. and the majority of studies investigating the effects of SARS-CoV-2 on the pancreas are clinical and observational, we utilized human iPSC technology to investigate the potential deleterious effects of SARS-CoV-2 infection on iPSC-derived pancreatic cultures containing endocrine and exocrine cells. Interestingly, iPSC-derived pancreatic cultures allow SARS-CoV-2 entry and establish infection, thus perturbing their normal molecular and cellular phenotypes. The infection increased a key cytokine, CXCL12, known to be involved in inflammatory responses in the pancreas. Transcriptome analysis of infected pancreatic cultures confirmed that SARS-CoV-2 hijacks the ribosomal machinery in these cells. Notably, the SARS-CoV-2 infectivity of the pancreas was confirmed in post-mortem tissues from COVID-19 patients, which showed co-localization of SARS-CoV-2 in pancreatic endocrine and exocrine cells and increased the expression of some pancreatic ductal stress response genes. Thus, we demonstrate that SARS-CoV-2 can directly infect human iPSC-derived pancreatic cells with strong supporting evidence of presence of the virus in post-mortem pancreatic tissue of confirmed COVID-19 human cases. This novel model of iPSC-derived pancreatic cultures will open new avenues for the comprehension of the SARS-CoV-2 infection and potentially establish a platform for endocrine and exocrine pancreas-specific antiviral drug screening.

In this study, the structure and photoelectrochemical properties of CuWO 4 porous films synthesized by a co-precipitation method followed by a hydrothermal treatment were investigated. The film was deposited on fluorine-doped tin oxide (FTO)-conducting glass, from a suspension containing polyethylene glycol, and heat-treated at 500 C for 30 min. X-ray diffraction patterns, the Rietveld refinement data, and the micro-Raman spectrum showed that the CuWO 4 film has a triclinic structure. The optical band gap energy of the film was estimated to be 2.45 eV by the Tauc plot. Field emission scanning electron microcopy images of the films indicated that they are about 4.0 AE 0.5 mm thick. The photoelectrochemical properties of the film were investigated in a Na 2 SO 4 aqueous solution, in the absence of light and under polychromatic irradiation. The CuWO 4 film exhibited photoelectrochemical behavior of a n-type semiconductor, with a negative photopotential and an anodic photocurrent density of 68 mA cm À2 at 0.73 V vs. Ag/AgCl (1.23 V vs. RHE). The n-type photoelectrochemical behavior was confirmed by a chronoamperometry measurement biased condition at + 0.7 V, at different pH values. From these studies, it was noted that when the pH values increased from 3 to 11, the photocurrent density increased about 9 times. Also, the flat band potential (E fb) of the semiconductor was estimated by the Butler-Gärtner model at + 0.34 V, which was utilized to calculate the conduction band edge. The studies presented here reveal that the CuWO 4 porous film is a promising candidate to be applied as a photoanode in photocatalytic processes under irradiation by visible light.

ObjectivesBrown adipose tissue (BAT) and BAT-like adipose tissues, referred to as ‘beige’ adipose tissues uncouple respiration from ATP synthesis via uncoupling protein one (UCP-1). There is a sexual dimorphism with respect to beige and BAT tissues; pre-menopausal women have more BAT and are more sensitive to BAT activation than men or postmenopausal women. We hypothesized selective activation of adipose tissue estrogen receptor alpha (ERα) induces beiging of WAT through induction of lipolysis mediated by adipose tissue triglyceride lipase (ATGL).Methods3T3-L1 and primary adipocytes were treated with the selective ERα agonist pyrazole triol (PPT), and selection deletion of ERα (using siRNA) was used to determine if selective ERα activation, or inhibition, influences the adipose tissue expression of genes associated with beiging. In a second series of experiments, ERα was selectively added back to adipose tissue of mice lacking total body ERα (ERKO) to determine if add back of ERα changed the morphology of adipose tissue to resemble beige tissues. Additionally, WT and ERKO mice were exposed to cold and FDG labeled glucose uptake was measured to determine the ability of cold to induce UCP-1 in ERKO mice. To begin to mechanistically probe how activation of ERα facilitates beiging, we tested the influence of PPT to activate the lipolytic pathway through ATGL. Finally, since ERα exerts its effects both at the genomic and non-genomic level depending on its cellular location, we determined in vivo if beiging occurs in mice expressing ERα only at the plasma membrane (MOER mice) or only at nucleus (NOER mice).ResultsSelective ERα activation by PPT increased markers of beiging in vitro in 3T3-L1 and primary adipocytes, whereas, knockdown of ERα with siRNA reduced the ability of PPT to induce beiging in vitro. ERα add back to the adipose tissue of ERKO mice resulted in multilocular adipose tissue resembling a beige phenotype. Following cold exposure, FDG labeled glucose in BAT tissues of ERKO mice was reduced when compared to weight-matched controls. Glycerol release and ATGL expression were increased after PPT treatment, while pre-treatment with the ATGL inhibitor prevented PPT's ability to increase UCP-1 expression. Finally, MOER mice were more sensitive to beiging of adipose tissues when compared to NOER mice.ConclusionOur results demonstrate for the first time that selective-activation of ERα in adipocytes increases markers of beiging and this is likely through induction of AMPK and ATGL-mediated lipolysis providing FFAs as a fuel to activate UCP-1.

In this Essay, we discuss the critical need to incorporate sex and gender in pre-clinical and clinical research to enhance our understanding of the mechanisms by which metabolic processes differ by sex and gender. This knowledge will allow for development of personalized medicine which will optimize therapies specific for individuals.

Background17 Alpha-estradiol (17 α-E2) is a natural, non-feminizing stereoisomer of 17 beta-estradiol (17 β-E2). Whereas much is known about the physiological effects of 17 β-E2, much less is known about 17 α-E2. For example, 17 β-E2 exerts anti-inflammatory effects in neurons and adipocytes through binding and activation of estrogen receptor alpha (ERα); however, if 17 α-E2 has similar effects on inflammation is currently unknown.MethodsTo begin to address this, we analyzed the ability of 17 α-E2 and 17 β-E2 to suppress lipopolysaccharide (LPS)-induced inflammation in vitro using embryonic fibroblast cells (MEF) from wild type and total body ERα (ERKO) male and female mice. Additionally, we further probed if there were sex differences with respect to the effects of E2s using primary pre-adipocyte cells from C57BL/6J male and female mice. Also, we probed mechanistically the effects of E2s in fully differentiated 3T3-L1 cells.ResultsBoth E2s decreased LPS-induced markers of inflammation Tnf-α and Il-6, and increased the anti-inflammatory markers Il-4 and IL-6 receptor (Il-6ra) in MEF cells. To begin to understand the mechanisms by which both E2’s mediate their anti-inflammatory effects, we probed the role of ERα using two methods. First, we used MEF cells from ERKO mice and found reductions in ERα diminished the ability of 17 α-E2 to suppress Tnf-α in female but not in male cells, demonstrating a sexual dimorphism in regard to the role of ERα to mediate 17 α-E2’s effects. Second, we selectively reduced the expression of ERα in 3T3-L1 cells using siRNA and found reductions in ERα diminished the ability of both E2s to suppress Tnf-α and Il-6 expression. Lastly, to determine the mechanisms by which E2s reduce inflammation, we explored the role of NFκB-p65 and found both E2s decreased NFκB-p65 expression.ConclusionsIn conclusion, we demonstrate for the first time that 17 α-E2, as well as 17 β-E2, suppresses inflammation through their effects on ERα and NFκB-p65.Electronic supplementary materialThe online version of this article (10.1186/s13293-017-0151-9) contains supplementary material, which is available to authorized users.

In this paper, a new synthesis method was proposed to obtain anatase titanium oxide (TiO 2) nanocrystals anchored into SBA-15 molecular sieve, as a matrix assigned by the in-situ anchoring (ISA) method. Pure SBA-15 and modified with TiO 2 nanocrystals at different Si/Ti molar ratios (R = 75, 50, and 25) were structurally characterized by X-ray diffraction (XRD), Micro-Raman and Fourier Transform infrared (FTIR) spectroscopies. Specific surface area, pore volume and average pore diameter were estimated using both Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH) methods, respectively. Morphological aspects of these samples were observed by means of field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). Optical properties were investigated by ultravioletvisible (UV-vis) diffuse reflectance spectroscopy. XRD patterns, Micro-Raman and FT-IR spectra indicate the TiO 2 nanocrystals crystallized in a tetragonal structure anchored into the SBA-15 mesopores. BET and BJH methods prove a large amount of TiO 2 nanocrystals were anchored inside of SBA-15 mesopores due to increase in surface area and average pore size of SBA-15 matrix. FE-SEM and TEM images showed the pure SBA-15 has an elongated hexagon-shaped microstructure, and an average size of 7.34 nm for 2D hexagonal mesopores. Moreover, ISA method was able to avoid blocking of mesopores, in addition promotes a significant increasing the impregnation rate of anatase TiO 2 nanocrystals in SBA-15 matrix. A growth mechanism was proposed in order to explain the stages involved in the formation of TiO 2-SBA mesoporous. UV-vis spectra revealed a dependence of the optical band gap energy (E gap) with the decreasing of Si/Ti molar ratios.