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Previous cross-sectional studies suggested that people with physical disabilities (one of the subgroups of disabled people) are associated with an increased risk of cardiovascular diseases (CVD) than healthy peers. However, a longitudinal cohort of disabled people exhibited a different trend, in which the study populations were similar in health inequalities. We aimed to examine whether physical disability was associated with an increased risk of coronary heart disease (CHD) among disabled people. This retrospective cohort study from the Shanghai Health Examination Program included a total of 6419 disabled adults (50.77 [9.88] age) with complete electronic health records and were free of CHD at baseline (2012) were followed-up for a 7.5-year period until 2019. The physical disability and non-physical disability subgroups were characterized based on the Disability Classification and Grading Standard (GB/T 26341–2010). Multivariable Cox regression analyses were used to evaluate adjusted hazard ratios (HR) for subsequent CHD, while Kaplan-Meier curves was used to assess the proportional hazards assumption. We conducted subgroup analyses based on gender, levels of disability, and baseline blood pressure. Kaplan-Meier analysis revealed a higher incidence of CHD in the physical disability group compared to the non-physical disability group during the 7.5-year follow-up period (P < 0.05). Subjects with physical disabilities exhibited an increased risk for subsequent CHD occurrence (HR : 1.12; 95% CI : 1.03–1.31), compared to the non-physical subgroup after adjustments for confounders. The sensitivity analysis conducted on subgroups according to gender and disability severity indicated that moderate physical disability and female physical disability were associated with a higher prevalence of CHD, which was confirmed by multi-adjusted regression analysis. The spline curves of BP and CHD indicated that the physical disability group displayed lower SBP and DBP thresholds of 120 mmHg and SBP, respectively. Within the disabled population, individuals with physical disability are at higher risk of developing CHD, and it is plausible that their optimal BP threshold for CHD prevention may need to be set at a lower level. Further research is essential to investigate BP management among individuals with physical disabilities and its influence on cardiovascular-related adverse events. [ABSTRACT FROM AUTHOR]

Background: Ciliary neurotrophic factor is a member of the interleukin‐6 family of cytokines. Ciliary neurotrophic factor drives many cells for their development. However, its effects on Leydig cell development remain unclear. Methods: In the current study, we used three‐dimensional seminiferous tubule culture system to induce the proliferation and differentiation of tubule‐associated stem Leydig cells and primary progenitor Leydig cells culture to address the effects of ciliary neurotrophic factor. Results: We found that ciliary neurotrophic factor stimulated the proliferation of stem Leydig cells but inhibited their development into the Leydig cell lineage. The ciliary neurotrophic factor‐mediated effects can be reversed by signal transducer and activator 3 inhibitor S3I‐201 and phosphatidylinositol 3‐kinase inhibitor wortmannin, indicating that ciliary neurotrophic factor acts via signal transducer and activator 3–phosphatidylinositol 3‐kinase signaling pathways to increase stem/progenitor Leydig cell proliferation. Ciliary neurotrophic factor at 1 and 10 ng/mL significantly decreased androgen production by progenitor Leydig cells. Microarray analysis of ciliary neurotrophic factor‐treated progenitor Leydig cells showed that ciliary neurotrophic factor blocked steroidogenic pathways by downregulating Scarb1, Star, and Hsd3b1, possibly by downregulating the transcription factor Nr5a1 expression. Conclusion: Ciliary neurotrophic factor stimulates proliferation but blocks the differentiation of stem/progenitor Leydig cells. [ABSTRACT FROM AUTHOR]

The discussion of collective agency involves the reduction problem of the concept of a collective. Individualism and Cartesian internalism have long restricted orthodox theories and made them face the tension between an irreducible concept of a collective and ontological reductionism. Heterodox theories as functionalism and interpretationism reinterpret the concept of agency and accept it as realized on the level of a collective. In order to adequately explain social phenomena that have relations as their essence, in this paper we propose a relational, holistic account of collective agency and argue that functionalism and interpretationism can be integrated into such an account. [ABSTRACT FROM AUTHOR]

Besides, MUC1 deficiency has been demonstrated to reduce CLDN1 expression in AR pathogenesis.3 Taken together, these results suggest that CLDN1 ubiquitination regulated by RBFOX3 may be involved in MUC1-mediated AR pathogenesis. MUC1 deficiency induces the nasal epithelial barrier dysfunction via RBFOX3 shortage augment ubiquitin-proteasomal degradation in allergic rhinitis pathogenesis In conclusion, our study demonstrates MUC1 deficiency inhibits CLDN1 expression I via i RBFOX3 shortage augment ubiquitin-proteasomal degradation in AR. [Extracted from the article]

In transition-metal dipnictides TmPn2 (Tm = Ta and Nb; Pn = P, As, and Sb), the origin of extremely large magnetoresistance (XMR) is yet to be studied by the direct visualization of the experimental band structures. Here, using angle-resolved photoemission spectroscopy, we map out the three-dimensional electronic structure of NbAs2. The open-orbit topology contributes to a non-negligible part of the Fermi surfaces (FSs), like that of the isostructural compound MoAs2, where the open FS is proposed to likely explain the origin of XMR. We further demonstrate the observation of open characters in the overall FSs of W2As3, which is also a XMR semimetal with the same space group of C12/m1 as the TmPn2 family and MoAs2. Our results suggest that the open-orbit FS topology may be a shared feature between XMR materials with the space group of C12/m1 and, thus, could possibly play a role in determining the corresponding XMR effect together with the electron–hole compensation. [ABSTRACT FROM AUTHOR]

Background: The cylindromatosis (CYLD) tumor suppressor is a microtubule‐associated deubiquitinase that plays a critical role in the regulation of cell signaling and contributes to a variety of physiological and pathological processes. However, the functions of CYLD in zebrafish are less well known, particularly with regard to their development and physiology. In this context, we investigated the loss of function of CYLD in zebrafish via transcription activator‐like effector nuclease (TALEN)‐based gene deletion. Methods: Semi‐quantitative RT‐PCR was used to quantify CYLD mRNA expression in zebrafish embryos at various developmental stages. We also performed whole‐mount in situ hybridization to further assess the dynamic expression and distribution of CYLD in the entire zebrafish embryos at different stages. In addition, we deleted CYLD in zebrafish with TALENs to investigate its potential impact on embryonic development. Results: The expression of CYLD mRNA varied during early embryonic development. The CYLD mRNA localized to the brain and notochord of developing zebrafish embryos. Homozygous deletion of CYLD resulted in embryonic death before 8 h post‐fertilization. Conclusions: CYLD appears to play an important role in central nervous system development in zebrafish. Although severe embryonic death restricted analysis of homozygous mutants, further research into the role of CYLD in central nervous system development is warranted. [ABSTRACT FROM AUTHOR]

We investigate the interface between a three-dimensional Dirac semimetal Cd3As2 and a normal metal via soft-point contact spectroscopy measurement. The superconducting gap features were detected below 3.8 K and 7.1 K in the case of Cd3As2 single crystals sputter-coated with the Pt and Au films, respectively, in the differential conductance dI/dV–V plots of the point contacts. As the applied magnetic field increased, the drop in the zero-bias contact resistance shifted toward lower temperatures. The topologically non-trivial band structure of Cd3As2 is considered to play a crucial role in inducing the superconductivity. Apart from realizing superconductivity in topological materials, our creative approach can be used to investigate possible topological superconductivity and exhibits a high application potential in electronic devices. [ABSTRACT FROM AUTHOR]

Objective: In this study, a genetic risk score (GRS) for the body mass index (BMI) tested and built using a large sample of Chinese individuals aged at least 50 years in southern China. We collected information regarding the participants' weights at 20 years of age and middle age and tested the BMI‐GRS effect modes. Methods: This study involved a prospective study design. The genetic data of the participants in from the Guangzhou Biobank Cohort Study and selected BMI‐related single‐nucleotide polymorphisms (SNPs) were used to establish the GRS. Results: We included 13 597 participants with 12 SNPs. After adjusting for covariates, the high‐GRS group was 36% (95% CI: 25%‐48%) and 34% (95% CI: 23%‐47%) more likely of being overweight at baseline and follow‐up, respectively, and 56% (95% CI: 34%‐82%) and 49% (95% CI: 29%‐72%) more likely of being obese at baseline and follow‐up, respectively, compared with the low‐GRS group (P‐value for all trends <.05). The RRs for the incidences of metabolically healthy and unhealthy obese (MHO and MUO, respectively) individuals in the high‐GRS group were 0.94 (95% CI: 0.65‐1.35) and 1.28 (95% CI: 1.00‐1.63), respectively. Conclusion: High‐GRS participants were more likely to be overweight/obese at baseline and follow‐up, and this relationship exhibited a dose‐response relationship. The GRS was also associated with MUO. [ABSTRACT FROM AUTHOR]

Human placental CYP19A1 catalyzes the estrogen synthesis from androgens. The enzyme is encoded by CYP19A1 gene located in chromosome 15q21. This enzyme is a monooxygenase in the smooth endoplasmic reticulum. The various promoters of the CYP19A1 gene determine its expression in different tissues and the distal promoter I.1 controls its expression in the placenta and retinoids can regulate the expression. Many food components and environmental chemicals inhibit CYP19A1 activity via different modes of action. These chemicals include gossypol, flavones, flavanones, chalconoids, resveratrol, and tobacco alkaloids derived from foods as well as phthalates, insecticides, fungicides, and biocides in the contaminated foods. The inhibition of placental CYP19A1 could impair pregnancy. • Human placental CYP19A1 catalyzes the estrogen synthesis from androgens. • Placental CYP19A1 prevents the female fetus from the androgenic effect of fetal androgens. • Food components and environmental chemicals in the contaminated foods are anti-estrogens via inhibiting CYP19A1 activity. • Some chemicals have clear structure-activity-response to inhibit CYP19A1 leading to disrupted pregnancy. [ABSTRACT FROM AUTHOR]

Abstract The inability of cultured primary Leydig cells to maintain luteinizing hormone (LH)-responsive testosterone formation in vitro for more than 3–5 days has presented a major challenge in testing trophic effects of regulatory factors or environmental toxicants. Our primary objective was to establish culture conditions sufficient to maintain LH-responsive testosterone formation by Leydig cells for at least a month. When isolated rat adult Leydig cells were cultured in DMEM/F12 and M199 culture medium containing insulin (10μg/ml), PDGFAA (10 ng/ml), lipoprotein (0.25 mg/ml), horse serum (1%) and a submaximal concentration of LH (0.2 ng/ml), the cells retained the ability to produce testosterone in vitro for at least 4 weeks. By using the longer-term culture conditions of this system, we were able to detect suppressive effects on testosterone production by low levels of the toxicant MEHP (mono-(2-ethylhexyl) phthalate), an active metabolite of the plasticizer DEHP, that were not detected by short-term culture. Highlights • A novel culture medium for the long-term maintenance of primary Leydig cells in vitro. • Insulin and PDGFAA play important roles in maintaining steroidogenesis in vitro. • LHCGR and CYP17A1 are particularly sensitive to long-term culture. • The long-term culture system is useful to test chronic effects of environmental toxins. [ABSTRACT FROM AUTHOR]

Little is known about the roles of dynorphin and Kappa opioid receptor (KOR) in mollusks. In this study, we aim to determine the distribution of dynorphin A and KOR-1 in the digestive system of the scallop Chlamys farreri. Using immunohistochemical staining, we confirmed the expression of dynorphin A and KOR-1 in the digestive system of C. farreri. Dynorphin A immunopositive cells were identified in intestine and hepatopancreas. In intestine, small and spherical dynorphin A immunopositive cells (4–9 μm in diameter) were scattered among the long columnar epithelial cells (ECs). In hepatopancreas, cells containing masses (5–14 μm in diameter) of dynorphin A immunopositive products were observed in epithelium of acinis. These immunopositive cells may be synthetic and/or secretory cells of dynorphin A. Dynorphin A immunoreactive products were commonly observed in epithelium and connective tissue (CT) of labial palps, mouth labia and stomach, which presented in forms of grains, fibers or flakes. KOR-1 immunoreactive material was observed in ECs and CTs of labial palps, mouth labia and stomach, intestine and hepatopancreas. The distribution of both dynorphin A and KOR-1 in the digestive organs suggests an involvement of dynorphin via KOR-1 in the functional regulation of the digestive system of C. farreri. [ABSTRACT FROM AUTHOR]

Inflammation causes male hypogonadism. Several inflammatory cytokines, including interleukin 6 (IL-6), are released into the blood and may suppress Leydig cell development. The objective of the present study was to investigate whether IL-6 affected the proliferation and differentiation of rat stem Leydig cells. Leydig cell-depleted rat testis ( in vivo ) and seminiferous tubules ( in vitro ) with ethane dimethane sulfonate (EDS) were used to explore the effects of IL-6 on stem Leydig cell development. Intratesticular injection of IL-6 (10 and 100 ng/testis) from post-EDS day 14 to 28 blocked the regeneration of Leydig cells, as shown by the lower serum testosterone levels (21.6% of the control at 100 ng/testis dose), the down-regulated Leydig cell gene ( Lhcgr , Star , Cyp11a1 , Cyp17a1 , and Hsd17b3 ) expressions, and the reduced Leydig cell number. Stem Leydig cells on the surface of the seminiferous tubules were induced to enter the Leydig cell lineage in vitro in the medium containing luteinizing hormone and lithium. IL-6 (1, 10, and 100 ng/ml) concentration-dependently decreased testosterone production and Lhcgr , Cyp11a1 , Cyp17a1 , Hsd17b3 and Insl3 mRNA levels. The IL-6 mediated effects were antagonized by Janus kinase 1 (JAK) inhibitor (filgotinib) and Signal Transducers and Activators of Transcription 3 (STAT3) inhibitor (S3I-201), indicating that a JAK-STAT3 signaling pathway is involved. In conclusion, our results demonstrated that IL-6 was an inhibitory factor of stem Leydig cell development. [ABSTRACT FROM AUTHOR]

Ziram is an endocrine disruptor and may cause birth abnormality of the male reproductive system. However, the effects of ziram on fetal Leydig cell (FLC) development are still unknown. The objective of the present study was to determine the endocrine-disrupting effect of ziram on rat FLC development after gestational exposure. Pregnant Sprague Dawley dams were randomly divided into 5 groups and were gavaged with 0 (corn oil, the control), 1, 2, 4, or 8 mg/kg ziram from gestational day 12 (GD12) to GD21. FLC development was evaluated by measuring serum testosterone, FLC number and distribution, and the expression levels of Leydig and Sertoli cell genes. Ziram significantly increased serum testosterone level at 1 mg/kg (1.350 ± 0.099 ng/ml vs. 0.989 ± 0.106 ng/ml in the control), while it remarkably lowered it at 8 mg/kg (0.598 ± 0.086 ng/ml). Quantitative immunohistochemical staining showed that ziram increased FLC number via stimulating cell proliferation at 1 mg/kg and lowered it via inhibiting its proliferation at 8 mg/kg without affecting Sertoli cell number. Further study demonstrated that the expression of Nr5a1 , Lhcgr , Scarb1 , Star , Cyp11a1 , and Cyp17a1 genes and proteins in the testis was upregulated at 1 mg/kg and the expression of Leydig ( Nr5a1 , Lhcgr , Scarb1 , Star , Cyp11a1 , Cyp17a1 , and Insl3 ) and Sertoli cell ( Fshr , Hsd17b3, Dhh, Amh , and Sox9 ) genes and proteins was downregulated by ziram at 8 mg/kg. In conclusion, ziram had biphasic effects on FLC development with low dose to increase FLC number and function and high dose to decrease them. [ABSTRACT FROM AUTHOR]

This paper presents a logic of preference and functional dependence (LPFD) and its hybrid extension (HLPFD), both of whose sound and strongly complete axiomatization are provided. The decidability of LPFD is also proved. The application of LPFD and HLPFD to modelling cooperative games in strategic form is explored. The resulted framework provides a unified view on Nash equilibrium, Pareto optimality and the core. The philosophical relevance of these game-theoretical notions to discussions of collective agency is made explicit. Some key connections with other logics are also revealed, for example, the coalition logic, the logic of functional dependence and the logic of ceteris paribus preference. [ABSTRACT FROM AUTHOR]

Adult Leydig cells develop from undifferentiated mesenchymal-like stem cells (stem Leydig cells, SLCs) present in the interstitial compartment of the early postnatal testis. Putative SLCs also have been identified in peritubular and perivascular locations of the adult testis. The latter cells, which normally are quiescent, are capable of regenerating new Leydig cells upon the loss of the adult cells. Recent studies have identified several protein markers to identify these cells, including nestin, PDGFRα, COUP-TFII, CD51 and CD90. We have shown that the proliferation of the SLCs is stimulated by DHH, FGF2, PDGFBB, activin and PDGFAA. Suppression of proliferation occurred with TGFβ, androgen and PKA signaling. The differentiation of the SLCs into testosterone-producing Leydig cells was found to be regulated positively by DHH (Desert hedgehog), lithium-induced signaling and activin; and negatively by TGFβ, PDGFBB, FGF2, Notch and Wnt signaling. DHH, by itself, was found to induce SLC differentiation into LH-responsive steroidogenic cells, suggesting that DHH plays a critical role in the commitment of SLC into the Leydig lineage. These studies, taken together, address the function and regulation of low turnover stem cells in a complex, adult organ, and also have potential application to the treatment of androgen deficiency. [ABSTRACT FROM AUTHOR]

A bifunctional highly-loaded NiMoW catalyst was prepared via hydrothermal reaction method with the incorporation of USY zeolite during synthetic process of precursor. The obtained samples were characterized by N 2 physisorption, XRD, Py-FTIR, and HRTEM. Combined with 4,6-DMDBT HDS activity results, Brønsted acid sites have been successfully generated in catalysts, and facilitated the demethylation and cracking reaction, as well as the DDS activity. The high activity of thus-achieved bifunctional catalysts can be attributed to the appropriate acid amount and the synergistic effect of Lewis and Brønsted acid sites combining with desirable textural properties and suitable stacking morphology of MoS 2 /WS 2 slabs. [ABSTRACT FROM AUTHOR]

Leukemia inhibitory factor (LIF) has many physiological roles. However, its effects on Leydig cell development are still unclear. Rat immature and adult Leydig cells were cultured with different concentrations of LIF alone or in combination with luteinizing hormone (LH) for 24 h. LIF (1 and 10 ng/ml) significantly increased androgen production in immature Leydig cells, but had no effects on testosterone production in adult Leydig cells. Further studies revealed that LIF dose-dependently increasedStarandHsd17b3expression levels in immature Leydig cells. Gene microarray revealed that the upregulation of anti-oxidative genes andStarmight contribute to LIF-induced androgen production. In conclusion, LIF has stimulatory effects on androgen production in rat immature Leydig cells. [ABSTRACT FROM PUBLISHER]

Oxidic unsupported Ni–Mo–W catalysts were prepared from a precipitate by high-temperature hydrothermal synthesis. The catalysts were sulfided in-situ by CS 2 and H 2 under different sulfiding conditions. The catalytic activity and selectivity were studied in the model reactions of naphthalene hydrogenation (HYD), quinoline hydrodenitrogenation (HDN), and dibenzothiophene (DBT) hydrodesulfurization (HDS). The sulfided catalysts were characterized by X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), and energy dispersive spectrum (EDS) mapping. Sulfided unsupported Ni–Mo–W catalysts showed visible diffraction peaks of Ni 3 S 2 and MoS 2 /WS 2 . As the sulfiding temperature or time increased, the Ni 3 S 2 and MoS 2 /WS 2 nanoparticles agglomerated, with MoS 2 /WS 2 lamella curved to some extent. Specifically, the stacking of the MoS 2 /WS 2 slabs increased with increasing sulfidation time. Meanwhile, the catalysts showed higher HDS, HDN, and HDAr activities when the sulfiding temperature was 320 °C. However, the hydrogenation activity decreased above 340 °C. [ABSTRACT FROM AUTHOR]

In this study, a cytochemical method and transmission electron microscopy was used to examine acid phosphatase activities of yolk granules throughout the early developmental stages of the Pacific oyster Crassostrea gigas. This study aimed to investigate the dynamic change of yolk granule acid phosphatase, and the mechanisms underlying its involvement in yolk degradation during the early developmental stages of molluscs. Three types of yolk granules (YGI, YGII, and YGIII) that differed in electron density and acid phosphatase reaction were identified in early cleavage, morula, blastula, gastrula, trochophore, and veliger stages. The morphological heterogeneities of the yolk granules were related to acid phosphatase activity and degrees of yolk degradation, indicating the association of acid phosphatase with yolk degradation in embryos and larvae of molluscs. Fusion of yolk granules was observed during embryogenesis and larval development of C. gigas. The fusion of YGI (free of acid phosphatase reaction) with YGII (rich in acid phosphatase reaction) could be the way by which yolk degradation is triggered. [ABSTRACT FROM AUTHOR]

Two novel 3d‐4f clusters with {CoII6LnIII2} (Ln = Dy (1), Ho (2)) cores are fabricated, with formulas of {[Co6Ln2(O)2(dhpb)6(NO3)2(DMF)2]·H2O} (H2dhpb = 6,6′‐dihydroxyl‐2,2′‐bipyridine, DMF = dimethyl formamide), which consist of two asymmetrical [Co3Ln] pyrimids bridged by a μ4‐O bridge. The {CoII6LnIII2} core exhibits a bicapped anti‐trigonal‐prism configuration, and is held together by six dhpb2− ligands. Interestingly, the LnIII ions are seven‐coordinate in pseudo‐D5h symmetry. The magnetic studies indicate that both compounds 1 and 2 show significant single‐molecule magnet (SMM) behaviours. [ABSTRACT FROM AUTHOR]

In this study, the subpopulations of coelomocytes of sea cucumber Apostichopus japonicus were identified with differential-interference microscope and flow cytometry (FCM). The immunostimulatory potential of crude lentinan (cLNT) from shiitake mushrooms ( Lentinus edodes) on A. japonicus was then investigated both in vitro and in vivo. In vitro, the coelomocytes of A. japonicus were incubated with different concentrations of cLNT (0, 2.5, 7.5, 22.5 mg/L) for 1 h, and immuno assays were performed. Flow cytometric analysis revealed that phagocytic activity and viability of coelomocytes increased significantly with cLNT treatment. Biochemical analysis showed a significant increase in peroxidase and alkaline phosphatase activity in coelomocytes. In vivo, the immunostimulatory effect of cLNT on coelomocytes was investigated with FCM by feeding A. japonicus with cLNT-supplemented or control diet for 24 days. The phagocytic activity of coelomocytes in cLNT treatment group was significantly increased at 4, 8 and 12 days of feeding. The viability of coelomocytes was increased after 8 days of feeding. At 4, 8, 12 and 18 days of feeding, the number of small-sized and low granularity coelomocytes was reduced, while the number of large-sized and high granularity coelomocytes was increased compared to control diet. Collectively, our in vitro and in vivo studies suggest that cLNT derived from L. edodes clearly reveals immunostimulating effects on A. japonicus by increasing the viability and phagocytic activity of coelomocytes, and these findings suggest that dietary supplementation of cLNT might further improve the commercial production of sea cucumbers. [ABSTRACT FROM AUTHOR]

Background and Purpose: Prostate cancer remains a major public health burden worldwide. Polo like kinase 4 (PLK4) has emerged as a promising therapeutic target in prostate cancer due to its key roles in cell cycle regulation and tumour progression. This study aims to develop and characterize the novel curcumin analogue NL13 as a potential therapeutic agent and PLK4 inhibitor against prostate cancer. Experimental Approach: NL13 was synthesized and its effects were evaluated in prostate cancer cells and mouse xenograft models. Kinome screening and molecular modelling identified PLK4 as the primary target. Antiproliferative and proapoptotic mechanisms were explored via cell cycle, apoptosis, gene and protein analyses. Key Results: Compared with curcumin, NL13 exhibited much greater potency in inhibiting PC3 (IC50, 3.51 μM vs. 35.45 μM) and DU145 (IC50, 2.53 μM vs. 29.35 μM) prostate cancer cells viability and PLK4 kinase activity (2.32 μM vs. 246.88 μM). NL13 induced G2/M cell cycle arrest through CCNB1/CDK1 down‐regulation and triggered apoptosis via caspase‐9/caspase‐3 cleavage. These effects were mediated by PLK4 inhibition, which led to the inactivation of the AKT signalling pathway. In mice, NL13 significantly inhibited tumour growth and modulated molecular markers consistent with in vitro findings, including decreased p‐AKT and increased cleaved caspase‐9/3. Conclusion and Implications: NL13, a novel PLK4‐targeted curcumin analogue, exerts promising anticancer properties against prostate cancer by disrupting the PLK4‐AKT‐CCNB1/CDK1 and apoptosis pathways. NL13 represents a promising new agent for prostate cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Although research has explored the association between atherogenic index of plasma (AIP) and prediabetes and diabetes, there is still not sufficient available evidence the role of physical activity (PA) in this relationship. Our purpose is to examine the complex connections between AIP, PA, and prediabetes and diabetes in a young and middle‐aged population. Methods: This study included 2220 individuals from the general population, aged 20–60 years. AIP was calculated from the logarithm of the triglyceride (TG) to high‐density lipoprotein cholesterol (HDL‐C) ratio. PA was assessed depending to the American Heart Association (AHA) criteria and categorized into medium‐high and low PA levels. We used binary logistic regression to explore associations and subsequently performed sensitivity and subgroup analyses. Results: The 2220 participants had a mean age of 38 years, with a mean AIP of −0.1185, and a prediabetes and diabetes prevalence of 7.2%. After adjusting for auxiliary variables, AIP was positively correlated with prediabetes and diabetes (odds ratio [OR]: 3.447, 95% confidence interval [CI]: 1.829–6.497). In the low PA population, the prevalence of prediabetes and diabetes raised significantly with higher AIP (OR: 3.678, 95% CI: 1.819–7.434). This association was not meaningful in the medium to high PA population (OR: 1.925, 95% CI: 0.411–9.007). Joint and sensitivity analyze results also showed agreement. Restricted cubic spline identified a linear relationship between AIP and the prevalence of prediabetes and diabetes. Notably, the prevalence significantly increases when AIP values exceed −0.16 (p for linearity <0.05). The findings revealed heterogeneity across subgroups stratified by sex and age. Conclusions: PA may modify the link as regards AIP with prediabetes and diabetes in young and middle‐aged populations. Adherence to PA prevents the adverse effects of abnormal glucose metabolism caused by dyslipidemia, particularly in women. [ABSTRACT FROM AUTHOR]

Acephate is an organophosphate pesticide. It is widely used. However, whether it inhibits androgen synthesis and metabolism remains unclear. In the current study, we investigated the effect of acephate on the inhibition of androgen synthetic and metabolic pathways in rat immature Leydig cells after 3-h culture. Acephate inhibited basal androgen output in a dose-dependent manner with the inhibition starting at 0.5 μM. It significantly inhibited luteinizing hormone and 8-Br-cAMP stimulated androgen output at 50 μM. It significantly inhibited progesterone-mediated androgen output at 50 μM. Further study demonstrated that acephate down-regulated the expression of Hsd3b1 and its protein at ≥ 0.5 μM, Lhcgr at 5 μM and Star at 50 μM. Acephate directly blocked rat testicular HSD3B1 activity at 50 μM. Acephate did not affect other androgen synthetic and metabolic enzyme activities as well as ROS production, proliferation, and apoptosis of immature Leydig cells. In conclusion, acephate targets LHCGR, STAR, and HSD3B1, thus blocking androgen synthesis in rat immature Leydig cells and HSD3B1 is being the most sensitive target of acephate. Image 1 • Acephate inhibits androgen synthesis. • Acephate down-regulates steroidogenic enzymes. • Acephate down-regulates cholesterol transport. • Acephate down-regulates LHCGR. [ABSTRACT FROM AUTHOR]

Dimethoate is an organophosphate pesticide. It is widely used in agriculture. However, whether it blocks pubertal development of Leydig cells remains unknown. In the current study, we exposed male Sprague Dawley rats with 7.5 and 15 mg kg−1 dimethoate from postnatal day 35–56. We also exposed Leydig cells isolated from 35-day-old rats for 3 h. Dimethoate reduced serum testosterone levels at 7.5 and 15 mg kg-1 but increased serum luteinizing hormone and follicle stimulating hormone levels at 15 mg kg-1. Dimethoate did not influence Leydig cell number but reduced Leydig cell size and down-regulated Star , Cyp11a1 , and Hsd3b1 in Leydig cells as well as their protein expression. Dimethoate inhibited basal androgen output in a dose-dependent manner with the inhibition starting at 0.05 μM. It significantly inhibited luteinizing hormone and 8Br-cAMP stimulated androgen outputs at 50 μM. It significantly inhibited 22R-hydroxycholesterol and progesterone-mediated androgen outputs at 50 μM. Further study demonstrated that dimethoate also down-regulated the expression of Star , Cyp11a1 , and Hsd3b1 at 5 or 50 μM in vitro. Dimethoate did not directly inhibit rat testicular steroidogenic enzyme activities at 50 μM. In conclusion, dimethoate targets Star , Cyp11a1 , and Hsd3b1 transcription, thus blocking Leydig cell differentiation during puberty. Image 1 • Dimethoate inhibits androgen synthesis. •Dimethoate down-regulates steroidogenic enzymes. •Dimethoate down-regulates cholesterol transport. •Dimethoate blocks Leydig cell differentiation. [ABSTRACT FROM AUTHOR]

Amorphous magnesium substituted mesoporous aluminophosphate (AlPO) were prepared, characterized and used as catalysts for the transesterification of diethyl carbonate and dimethyl carbonate in the fixed-bed reactor. The results of FT-IR and XPS confirm the substitution of Mg into the framework of AlPO. Magnesium substituted mesoporous aluminophosphate (MgAPO) have strong basic and weak acid sites according to the results of CO 2 -TPD and NH 3 -TPD. Compared with that of the AlPO catalyst, the pore diameters of the catalysts increased after the introduction of Mg. The activity and stability of the catalysts also improved with the introduction of Mg. The catalytic performance of these catalysts increases in the order of AlPO < Mg 0.1 APO < Mg 0.3 APO < Mg 0.2 APO, which is consistent with the strong basic and weak acid amounts of the catalysts, indicating an acid-base synergistic catalysis in the reaction. The catalyst showed high stability after 960 h of time on stream. As a result, the Mg 0.2 APO presented remarkable activity and durability in the synthesis of ethyl methyl carbonate from dimethyl carbonate and diethyl carbonate in fixed-bed reactor. Image 1 • Magnesium substituted mesoporous aluminophosphate was prepared. • Mg 0.2 APO showed high catalytic performance for the synthesis of ethyl methyl carbonate. • Strong basic and weak acid sites were synergistic catalysis for the transesterification. • The catalyst exhibited high stability after 960 h of time on stream. [ABSTRACT FROM AUTHOR]

Background: : Oncostatin M (OSM) is a member of the interleukin‐6 group of cytokines, which can regulate cell proliferation, growth, and function. Immature Leydig cells have the ability to proliferate and differentiate, and adult Leydig cells have the function of testosterone synthesis. However, the role and underlying mechanisms of OSM on the proliferation and function of Leydig cells remain unclear. Methods: : The effects of OSM on the proliferation, apoptosis, and function of immature Leydig cells isolated from 35‐day‐old rats and the function of adult Leydig cells isolated from 63‐day‐old rats in vitro. Results: : OSM stimulated immature Leydig cell proliferation after up‐regulating the expression of Ccnd1 and Cdk4 to drive the transition of G1 phase to M2 phase in the cell cycle at 10 and 100 ng/ml. OSM did not affect the apoptosis of immature Leydig cells up to 100 ng/ml. OSM inhibited testosterone production in immature and adult Leydig cells by down‐regulating the expression of Lhcgr, Star, Cyp11a1, Hsd3b1, and Cyp17a1 at 1–100 ng/ml. OSM induced reactive oxygen species and down‐regulated the expression of antioxidant genes and lowered mitochondrial membrane potential at 10 and 100 ng/ml in both Leydig cells. Janus kinase 1 (JAK1) antagonist filgotinib and signal transducer and activator of transcription 3 (STAT3) antagonist S3I‐201 reversed the effect of OSM, indicating that it acts on JAK1/STAT3 signaling. Conclusion: : Oncostatin M stimulates immature Leydig cell proliferation while inhibiting the function of immature and adult Leydig cells. [ABSTRACT FROM AUTHOR]

Stem cells are specialized cells that can renew themselves through cell division and can differentiate into multi-lineage cells. Mesenchymal stem cells are adult stem cells that exist in animal and human tissues. Mesenchymal stem cells have the ability to differentiate into mesodermal lineages, such as Leydig cells, adipocytes, osteocytes, and chondrocytes. Mesenchymal stem cells express cell surface markers, such as cluster of differentiation (CD) 29, CD44, CD73, CD90, CD105, and lack the expression of CD14, CD34, CD45 and HLA (human leukocyte antigen)-DR. Stem Leydig cells are one kind of mesenchymal stem cells, which are present in the interstitial compartment of testis. Stem Leydig cells are multipotent and can differentiate into Leydig cells, adipocytes, osteocytes, and chondrocytes. Stem Leydig cells have been isolated from rodent and human testes. Stem Leydig cells may have potential therapeutic values in several clinical applications, such as the treatment of male hypogonadism and infertility. In this review, we focus on the latest research on stem Leydig cells of both rodents and human, the expression of cell surface markers, culture, differentiation potential, and their applications. [Display omitted] • Leydig cells develop from perivascular and peritubular stem Leydig cells. • Stem Leydig cells have some common biomarkers such as nestin. • When stem Leydig cells commit into the Leydig cell lineage with the expression of steroidogenic enzymes. • Some factors secreted by Sertoli cells are critical for stem Leydig cell differentiation such as desert hedgehog. • Some growth factors stimulate stem Leydig cell proliferation such as platelet-derived growth factor. [ABSTRACT FROM AUTHOR]

Background: Microorganism identification is critical for the early diagnosis and management of infectious endophthalmitis, but traditional culture can yield false‐negative results. Nanopore targeted sequencing (NTS) is a third‐generation sequencing technique with multiple advantages. This study aimed to test aqueous humour or vitreous fluid samples from presumed cases of infectious endophthalmitis using NTS to evaluate the feasibility of NTS in diagnosing endophthalmitis, especially for culture‐negative cases. Methods: This prospective study enrolled patients who presented to the Department of Ophthalmology of Union Hospital (Wuhan, China) between June 2018 and December 2020. The samples were sent immediately for routine microbiology culture processing and NTS assay. Results: NTS identified microorganisms in 17 of 18 cases (94.4%) (eight culture‐positive cases, nine culture‐negative cases, and one case unavailable for culture). There was a high‐quality match between culture and NTS for culture‐positive cases. In the eight culture‐negative cases and the case unavailable for culture, NTS detected either bacteria, fungi, or a mixture of bacteria and fungi in the intraocular fluids. The average waiting times for the results of bacterial and fungal cultures were 48 and 72 h, respectively. The average time for the NTS results was 12 h. Conclusions: NTS appears to be a promising diagnostic platform for diagnosing infectious endophthalmitis, even for culture‐negative cases. [ABSTRACT FROM AUTHOR]

• Dextmedetomidine concentration-dependently inhibits androgen production in immature Leydig cells. • Dextmedetomidine blocks androgen biosynthetic pathway and metabolizing pathway in immature Leydig cells. • Dextmedetomidine increases ROS generation in immature Leydig cells. • Dextmedetomidine induces apoptosis of immature Leydig cells. • Dextmedetomidine decreases EKR1/2 phosphorylation that could lead to lower steroidogenesis in the immature Leydig cells. Dexmedetomidine (DEX), an imidazole compound, is an anesthetic drug used perioperatively. In the current study, we investigated the effects of DEX on androgen production in rat immature Leydig cells in vitro. Leydig cells isolated from pubertal Sprague Dawley rats were treated with various concentrations of DEX (0.015–1.5 µM) for 3 h and medium 5α-androstanediol and testosterone levels and the expression of Lhcgr , Scarb1 , Star , Cyp11a1 , Hsd3b1 , Cyp17a1 , Hsd17b3 , Srd5a1 and Akr1c14 in Leydig cells were determined. At 0.015–1.5 μM, DEX concentration-dependently inhibited androgen secretion and downregulated Cyp17a1 and Srd5a1 mRNA levels. DEX equally blocked the LH- and cAMP-stimulated secretion of androgens. Using the steroid substrates, 22R-hydroxycholesterol (for cytochrome P450 cholesterol side chain cleavage), pregnenolone (for 3β-hydroxysteroid dehydrogenase 1), progesterone (for cytochrome P450 17α-hydroxylase/C17,C20-lyase), androstenedione (for 17β-hydroxysteroid dehydrogenase 3), testosterone (for steroid 5α-reductase 1), and dihydrotestosterone (for 3α-hydroxysteroid dehydrogenase), it was demonstrated that DEX inhibited 22R-hydroxycholesterol, pregnenolone, progesterone, and testosterone-mediated 5α-androstanediol formation at 1.5 μM. Further study demonstrated that DEX also directly inhibited rat testis cholesterol side chain cleavage, 3β-hydroxysteroid dehydrogenation, and 17α-hydroxylation at 1.5 μM. DEX induced ROS production and increased apoptosis rate in immature Leydig cells after 24-h treatment at ≥0.15 μM. In conclusion, DEX directly inhibits the activities of some steroidogenic enzymes and downregulates the expression of Cyp17a1 and Srd5a1 , and increases ROS production, thus leading to lower production of androgens in immature Leydig cells. [ABSTRACT FROM AUTHOR]

• Glucocorticoid binds to GR to inhibit testosterone production in Leydig cells. • Glucocorticoid binds to MR to stimulate testosterone production in Leydig cells. • 11β-Hydroxysteroid dehydrogenases control glucocorticoid levels in Leydig cells. • 11β-Hydroxysteroid dehydrogenase 1 direction is coupled by several steroidogenic enzymes. Glucocorticoid is secreted by adrenal cortex, which binds to intracellular glucocorticoid and mineralocorticoid receptors to regulate steroidogenesis-related gene expression and testosterone production in Leydig cells. Glucocorticoid receptor activity shows inhibitory action on Leydig cell steroidogenesis, while mineralocorticoid receptor activity shows the stimulatory action. Leydig cells contain two important glucocorticoid-metabolizing enzymes, 11β-hydroxysteroid dehydrogenase type 1 and type 2, regulating the intracellular levels of glucocorticoids by a pre-receptor mechanism. 11β-Hydroxysteroid dehydrogenase type 1 is a bidirectional enzyme, and its direction is regulated by intracellular NADP+/NADPH redox potential. Leydig cells contain many steroidogenic enzymes, possibly regulating NADP+/NADPH redox potential by coupling with 11β-hydroxysteroid dehydrogenase type 1. Here, we review the 11β-hydroxysteroid dehydrogenase regulation and possible consequences in Leydig cell biology and pathology. [ABSTRACT FROM AUTHOR]

Freshwater fish biodiversity is quickly decreasing and requires effective monitoring and conservation. Environmental DNA (eDNA)‐based methods have been shown to be highly sensitive and cost‐efficient for aquatic biodiversity surveys, but few studies have systematically investigated how spatial sampling design affects eDNA‐detected fish communities across lentic systems of different sizes. We compared the spatial patterns of fish diversity determined using eDNA in three lakes of small (SL; 3 ha), medium (ML; 122 ha) and large (LL; 4,343 ha) size using a spatially explicit grid sampling method. A total of 100 water samples (including nine, 17 and 18 shoreline samples and six, 14 and 36 interior samples from SL, ML and LL, respectively) were collected, and fish communities were analysed using eDNA metabarcoding of the mitochondrial 12S region. Together, 30, 35 and 41 fish taxa were detected in samples from SL, ML, and LL, respectively. We observed that eDNA from shoreline samples effectively captured the majority of the fish diversity of entire waterbodies, and pooled samples recovered fewer species than individually processed samples. Significant spatial autocorrelations between fish communities within 250 m and 2 km of each other were detected in ML and LL, respectively. Additionally, the relative sequence abundances of many fish species exhibited spatial distribution patterns that correlated with their typical habitat occupation. Overall, our results support the validity of a shoreline sampling strategy for eDNA‐based fish community surveys in lentic systems but also suggest that a spatially comprehensive sampling design can reveal finer distribution patterns of individual species. [ABSTRACT FROM AUTHOR]

Microplastics can combine with pollutants such as antibiotics and pose a threat to the environment and organisms. At the same time, the inevitable aging behavior of microplastics in the actual environment leads to changes in their physical and chemical properties, and thus changes the reaction mechanism between microplastics and other pollutants. In this study, we used three common microplastics PE/PS/PA to study the adsorption behavior of levofloxacin hydrochloride. Ultraviolet aging method was used to simulate the aging process of levofloxacin hydrochloride under sunlight, and compared with that of before aging. The results showed that the order of adsorption capacity was PS-UV > PA-UV > PE-UV > PA > PS > PE. Aging behavior can significantly enhance the adsorption capacity of microplastics to pollutants. Both Langmuir and Freundlich models can be used to fit the isothermal adsorption process well, indicating that the adsorption process was not a simple monolayer adsorption, but also a multi-molecular layer adsorption. The experiments showed that the adsorption process was affected by various mechanisms, including π-π conjugation, hydrogen bond, ion exchange and electrostatic interaction. This study elucidated the interaction mechanism between microplastics and levofloxacin hydrochloride, which has important significance for future control of microplastics and antibiotic pollution. [Display omitted] • High temperatures can break chemical bonds and inhibit the adsorption process. • The addition of humic acid shows an inhibitory effect on the adsorption process. • Low levels of Cr(VI) act as a promoter and high levels act as an inhibitor. • Micropore filling and wrinkles from UV ageing play a major role in adsorption. [ABSTRACT FROM AUTHOR]

Curcuminoids are functional food additives, and the effect on gonadal hormone biosynthesis remains unclear. Gonads contain 3β-hydroxysteroid dehydrogenase isoforms, h3β-HSD2 (humans) and r3β-HSD1 (rats), which catalyse pregnenolone into progesterone. The potency and mechanisms of curcuminoids to inhibit 3β-HSD activity were explored. The inhibitory potency was bisdemethoxycurcumin (IC50, 1.68 µM) >demethoxycurcumin (3.27 µM) > curcumin (13.87 µM) > tetrahydrocurcumin (109.0 µM) > dihydrocurcumin and octahydrocurcumin on KGN cell h3β-HSD2, while that was bisdemethoxycurcumin (1.22 µM) >demethoxycurcumin (2.18 µM) > curcumin (4.12 µM) > tetrahydrocurcumin (102.61 µM) > dihydrocurcumin and octahydrocurcumin on testicular r3β-HSD1. All curcuminoids inhibited progesterone secretion by KGN cells under basal and forskolin-stimulated conditions at >10 µM. Docking analysis showed that curcuminoids bind steroid-active site with mixed or competitive mode. In conclusion, curcuminoids inhibit gonadal 3β-HSD activity and de-methoxylation of curcumin increases inhibitory potency and metabolism of curcumin by saturation of carbon chain losses inhibitory potency. [ABSTRACT FROM AUTHOR]

• Benzyl butyl phthalate stimulates immature Leydig cell proliferation. • Benzyl butyl phthalate increases Leydig cell number. • Benzyl butyl phthalate inhibits androgen production at the high dose. • Benzyl butyl phthalate is metabolized into mono-benzyl phthalate that has potent toxicity. Benzyl butyl phthalate (BBP) is a widely used plasticizer and has raised public health concerns. Here, we report the effects of BBP on the testis development during rat puberty. BBP (0, 10, 100 or 1000 mg/kg) was gavaged to 35-day-old male Sprague Dawley rats for 21 days. The serum testosterone levels, Leydig cell number, the expressions of Leydig and Sertoli cell genes and proteins were measured. The in vitro effects on steroidogenesis and gene expression in immature Leydig cells were observed. BBP significantly increased serum testosterone level at 10 mg/kg but lowered its level at 1000 mg/kg without affecting serum luteinizing hormone and follicle-stimulating hormone levels. BBP increased Leydig cell number at all doses but inhibited steroidogenic capacity per Leydig cell at 1000 mg/kg. BBP significantly increased the ratio of phosphos-AKT2 (pAKT2)/AKT2, and phosphos-ERK1/2 (pERK1/2)/ERK1/2 in the testis. Mono-benzyl phthalate (the metabolite of BBP) inhibited steroidogenesis but BBP did not affect androgen production in immature Leydig cells in vitro. In conclusion, BBP non-linearly regulates Leydig cell development by increasing Leydig cell number but inhibiting steroidogenesis. [ABSTRACT FROM AUTHOR]

Abstract Testicular 3β-hydroxysteroid dehydrogenase (HSD3B) is a steroidogenic enzyme, catalyzing the conversion of 3β-hydroxysteroids into 3-keto-steroids. Two distinct isoforms in the human are cloned, HSD3B1 and HSD3B2, and HSD3B2 is located in the testis. HSD3B2 is a two-substrate enzyme, which binds to cofactor NAD+ and a 3β-steroid. Many endocrine disruptors, including industrial compounds (phthalates, bisphenols, and perfluoroalkyl substances), insecticides and biocides (organochlorine insecticides and organotins), food additives (butylated hydroxyanisole, resveratrol, gossypol, flavones, and isoflavones), and drugs (etomidate, troglitazone, medroxyprogesterone acetate, and ketoconazole) inhibit testicular HSD3B, possibly interfering with androgen synthesis. In this review, we discuss the distinct testicular isoform of HSD3B, its gene, chemistry, subcellular location, and the endocrine disruptors that directly inhibit testicular HSD3B and their inhibitory modes. Highlights • HSD3B catalyzes 3β-dehydrogenase of 3β-hydroxysteroids. • Testicular HSD3B is critical for testosterone synthesis. • There is a SAR difference for phthalate-mediated inhibition of HSD3B. • Some flavones and isoflavones are very potent HSD3B inhibitors. [ABSTRACT FROM AUTHOR]

Abstract Rational design of efficient and durable anode materials is particularly momentous for high-performance lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs). According to this concept, an effective strategy to prepare MoS 2 /N, S co-doped graphene by electrochemical exfoliation combining hydrothermal route is presented. Due to N and S atoms co-doping to graphene sheets, the three-dimensional interconnection of few-layered MoS 2 and graphene, which contribute to relieving the restacking of the two components, accelerating the electrons transport and improving Li/Na storage capacity. As an anode in LIBs, the MoS 2 /NSG-AG demonstrates an up to reversible capacity of 1012 mAh g−1 after cycling 300 times at 0.5 A g−1 and good rate performance with a capability of 1300.7, 1215.2, 1106.3, 1005.5, 892.7 and 727.7 mAh g−1 at 0.1, 0.2, 0.5, 1.0, 2.0 and 4.5 A g−1, respectively. Furthermore, it delivers a maximum energy density of 890 Wh kg−1 along with the power density of 130 W kg−1. Meanwhile, when used in SIBs, it displays a good reversible capacity of 320.9 mAh g−1 after cycling 500 times at 0.5 A g−1. The prominent electrochemical performance could be due to the three-dimensional network formed by interconnection of MoS 2 and graphene, co-doping of N and S, considerable surface area and rich mesoporous as well as the expanded layer spacing of graphene and MoS 2. Therefore, this is a facile strategy to obtain high-performance hetero-structured anode and make it great potential applications in LIBs and SIBs. [ABSTRACT FROM AUTHOR]

Background: The global prevalence of chronic kidney disease (CKD) in the general population is relatively clear. Our previous study showed that elderly individuals who are physically disabled are more likely to experience kidney function impairment, and the main purpose of this study was to determine the prevalence and risk factors associated with CKD in elderly patients with physical disabilities. Methods: A total of 2679 elderly individuals with physical disabilities from the 2018 Shanghai Disability Health Survey were screened to calculate the prevalence of CKD. Multiple logistic regression was performed to identify the factors associated with CKD. Detailed subgroup analyses of disability level were also conducted. Results: We confirmed CKD in 287 of 2679 (10.7%) participants. Female sex, age, history of hypertension, red blood cell count, albumin, urea, and uric acid (UA) were independently correlated with CKD. Age and UA abnormalities were common risk factors for different levels of disabilities. Conclusion: The prevalence of CKD is higher in the mild level of older physically handicapped individuals. Age and the level of UA should also be considered in this population. The preventive strategies for patients with two levels of elderly disability should have different focuses. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) analogues substituted on the benzene ring are widely used in a variety of industrial and consumer materials. However, their effects on the glucocorticoid-metabolizing enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) remain unclear. The inhibitory effects of 6 BPA analogues on the inhibition of human and rat 11β-HSD1 were investigated. The potencies of inhibition on human 11β-HSD1 were bisphenol H (IC50, 0.75 µM) > bisphenol G (IC50, 5.06 µM) > diallyl bisphenol A (IC50, 13.36 µM) > dimethyl bisphenol A (IC50, 30.18 µM) > bisphenol A dimethyl ether (IC50, 33.08 µM) > tetramethyl bisphenol A (>100 µM). The inhibitory strength of these chemicals on rat 11β-HSD1 was much weaker than that on the human enzyme, ranging from 74.22 to 205.7 µM. All BPA analogues are mixed/competitive inhibitors of both human and rat enzymes. Molecular docking studies predict that bisphenol H and bisphenol G both bind to the active site of human 11β-HSD1, forming a hydrogen bond with catalytic residue Ser170. The bivariate correlation of IC50 values with LogP (lipophilicity), molecular weight, heavy atoms, and molecular volume revealed a significant inverse regression and the correlation of IC50 values with ΔG (low binding energy) revealed a positive regression. In conclusion, the lipophilicity, molecular weight, heavy atoms, molecular volume, and binding affinity of a BPA analogue determine the inhibitory strength of human and rat 11β-HSD isoforms. [ABSTRACT FROM AUTHOR]

Temperature change affects human health and asthma.[[1]] Serum IgE concentrations were shown to be significantly lower in experimental asthmatic mice treated at thermoneutral (30°C) than those treated at standard housing temperature (20°C).[3] A recent study found that the exosomes of mast cells (MC) can compete with MC to bind serum IgE and reduce asthma symptoms.[4] This study aimed to investigate whether temperature directly affects MC-derived exosomes in mediating the high-affinity receptor for IgE (Fc RI)-dependent MC activation and ovalbumin-induced asthma. In summary, this study provides evidence of the temperature-dependent regulation of MC-derived exosomes through regulation of Rab3a expression, which protected against Fc RI-dependent MC activation in vitro and experimental asthma in vivo. Temperature regulates Rab3a and mast cell-derived exosomal Fc RI to inhibit mast cell activation. [Extracted from the article]

Benzophenones (BPs) are a class of chemicals found in various personal care and cosmetic products, such as sunscreens and lotions. Their usage is known to cause reproductive and hormonal health risks, but the exact mechanism of action remains unknown. In this study, we investigated the effects of BPs on human and rat placental 3β-hydroxysteroid dehydrogenases (3β-HSDs), which play a crucial role in the biosynthesis of steroid hormones, particularly progesterone. We tested inhibitory effects of 12 BPs, and performed structure-activity relationship (SAR) and in silico docking analysis. The potency of BPs to inhibit human 3β-HSD1 (h3β-HSD1) is BP-1 (IC 50 , 8.37 μM)>BP-2 (9.06 μM)>BP-12 (94.24 μM)>BP-7 (1160 μM) >BP-8 (1257 μM) >BP-6 (1410 μM) > other BPs (ineffective at 100 μM). The potency of BPs on rat r3β-HSD4 is BP-1 (IC 50 , 4.31 μM)>BP-2 (117.3 μM)>BP-6 (669 μM) >BP-3 (820 μM)>other BPs (ineffective at 100 μM). BP-1, BP-2, and BP-12 are mixed h3β-HSD1 inhibitors and BP-1 is a mixed r3β-HSD4 inhibitor. LogP, lowest binding energy, and molecular weight were positively associated with IC 50 for h3β-HSD1, while LogS was negatively associated with IC 50. The 4-OH substitution in the benzene ring plays a key role in enhancing the effectiveness of inhibiting h3β-HSD1 and r3β-HSD4, possibly through increasing water solubility and decreasing lipophilicity by forming hydrogen bonds. BP-1 and BP-2 inhibited progesterone production in human JAr cells. Docking analysis shows that 2-OH of BP-1 forms hydrogen bonds with catalytic residue Ser125 of h3β-HSD1 and Thr125 of r3β-HSD4. In conclusion, this study demonstrates that BP-1 and BP-2 are moderate inhibitors of h3β-HSD1 and BP-1 is a moderate inhibitor of r3β-HSD4. There is a significant SAR differences for 3β-HSD homologues between BPs and distinct species-dependent inhibition of placental 3β-HSDs. [Display omitted] • BP-1 and BP-2 potently inhibit placental human 3β-HSD1. • BP-1 potently inhibits placental rat 3β-HSD4. • BP-1 and BP-2 inhibit progesterone production by human JAr cells. • BP-2 is more potent to inhibit human 3β-HSD1 than rat 3β-HSD4. • LogP and LogS are correlated with the IC50 values of human 3β-HSD1. [ABSTRACT FROM AUTHOR]

In the testis, KIT ligand (KITL, also called stem cell factor) is expressed by Sertoli cells and its receptor (c-kit, KIT) is expressed by spermatogonia and Leydig cells. Although KITL-KIT signaling is critical for the spermatogenesis, its roles in Leydig cell development during puberty are not clear. In the present study, we investigated effects of KITL on stem Leydig cell proliferation and differentiation. Using an in vitro culture system of seminiferous tubules from Leydig cell-depleted testis, we found that KITL increased the proliferation activity of putative stem Leydig cells at higher concentration (10 and 100 ng/ml). Low concentration (1 ng/ml) of KITL significantly induced the differentiation of stem Leydig cells via increasing the expression level of steroidogenic acute regulatory protein ( Star ). In contrast, higher concentration (100 ng/ml) of KITL inhibited the differentiation of stem Leydig cells via inhibiting the steroidogenic enzyme ( Cyp11a1 , Cyp17a1 , and Hsd17b3 ) expression levels. We cultured rat progenitor Leydig cells with KITL for 48 h and did not find any influence of KITL on the proliferation and androgen production of these cells. In conclusion, KITL is a growth factor that regulates the development of the stem Leydig cell. [ABSTRACT FROM AUTHOR]

[Display omitted] Pursuing efficient thermoelectricity from low-dimensional materials has been highly motivated since the seminal work of Hicks and Dresselhaus. In fact, many superior thermoelectric materials like Bi 2 Te 3 , Mg 3 Sb 2 /Mg 3 Bi 2 and SnSe are quasi-two-dimensional (q2D), though the advantages of two-dimensionality appear to be diverse and sometimes controversial. Here, we report on a remarkably high thermoelectric performance in TlCu 3 Te 2 , which is quasi-one-dimensional (q1D) with a further reduced dimension. The thermoelectric figure of merit zT along its q1D axis amounts to 1.3 (1.5) at 300 (400) K, rivaling the best ever reported at these temperatures. The high thermoelectric performances benefit from, on one hand, large power factors derived from a center-hollowed, pancake-like Fermi pocket with q1D dispersion at the edge of a narrow band gap, and on the other hand, small lattice thermal conductivities caused by the large and anharmonic q1D lattice consisting of heavy, lone-pair-electron bearing (Tl+) and weakly-bonded (Cu+) ions. This compound represents the first bulk material with quasi-uniaxial thermoelectric transport of application level, offering a renewed opportunity to exploit reduced dimensionality for high-performance thermoelectricity. [ABSTRACT FROM AUTHOR]

Cold exposure is a common factor to trigger asthma attacks. However, the underlying mechanism has not been thoroughly elucidated. We aimed to investigate the hypothesis that low temperature reduces occludin expression and compromises epithelial barrier function in airways, which in turn, results in asthma exacerbation. We examined occludin expression in human bronchial epithelial cell line (Beas-2B) cells exposed to either 29 °C or 37 °C. The following drugs were administered prior to cold treatment: MG132 (a proteasome inhibitor), cycloheximide (a protein synthesis inhibitor), HC-067047 plus GSK2193874 (transient receptor potential vanilloid 4 [TRPV4] antagonists), or C4-ceramide (a glucocorticoid-inducible kinase [SGK1] activator). siNedd4–2 was transfected into Beas-2B cells to investigate the role that Nedd4–2 plays in mediating occludin instability induced by cold. In animal experiments, we treated ovalbumin (OVA)-induced asthmatic mice with a thermoneutral temperature of 30 °C or cold exposure (10 °C, 6 h/day) for 2 weeks. GSK2193874 or C4-ceramide was administered during the cold treatment. Occludin expression of the lung, pulmonary permeability, serum IgE levels, and lung inflammation were assessed. Low temperature treatment (29 °C) significantly reduced the expression of occludin in Beas-2B cells from 1 to 9 h, which was rescued upon treatment with MG132, HC-067047 plus GSK2193874, C4-ceramide, or Nedd4–2 knockdown. Low temperatures affected occludin stability through SGK1/Nedd4–2-dependent proteolysis. In vivo mice data revealed that cold exposure compromised the airway epithelial barrier function, decreased occludin expression, and exacerbated lung inflammation, which was attenuated by the GSK2193874 or C4-ceramide injection. We identified a potential mechanism underlying cold-induced asthma exacerbation involving Nedd4–2-mediated occludin proteolysis and airway epithelial barrier disruption. • Low temperature reduced occludin expression in bronchial epithelial cells. • Cold-induced occludin degradation was mediated by Nedd4-2-dependent proteolysis. • Reduced expression of tight junction proteins may lead to epithelial barrier dysfunction at low temperatures. • C4-ceramide improved occludin expression at low temperature. [ABSTRACT FROM AUTHOR]

3β-Hydroxysteroid dehydrogenase/steroid Δ5,4-isomerase 1 (3β-HSD1) plays a critical role in the biosynthesis of progesterone from pregnenolone in the human placenta to maintain normal pregnancy. Whether they inhibit placental 3β-HSD1 and mode of inhibition remains unclear. In this study, we screened 21 pesticides and fungicides in five classes to inhibit human 3β-HSD1 and compared them to rat homolog 3β-HSD4. 3β-HSD activity was measured by catalyzing pregnenolone to progesterone in the presence of NAD+. Of the 21 chemicals, azoles (difenoconazole), thiocarbamates (thiram and ferbam) and organochlorine (hexachlorophene) significantly inhibited human 3β-HSD1 with half maximal inhibitory concentration (IC 50) values of 2.77, 0.24, 0.68, and 17.96 μM, respectively. We also found that difenoconazole, ferbam and hexachlorophene are mixed/competitive inhibitors of 3β-HSD1 while thiram is a mixed/noncompetitive inhibitor. Docking analysis showed that difenoconazole and hexachlorophene bound steroid-binding site. Difenoconazole and hexachlorophene except thiram and ferbam also significantly inhibited rat 3β-HSD4 activity with IC 50 of 1.12 and 2.28 µM, respectively. Thiram and ferbam significantly inhibited human 3β-HSD1 possibly by interfering with cysteine residues, while they had no effects on rat 3β-HSD4. In conclusion, some pesticides potently inhibit placental 3β-HSD, leading to the reduction of progesterone formation. [Display omitted] • Difenoconazole, thiram, and ferbam are potent human 3β-HSD1 inhibitors. • Hexachlorophene is a moderate human 3β-HSD1 inhibitor. • The species-dependent difference for inhibition of placental 3β-HSD. • Thiram and ferbam inhibit human 3β-HSD1 by targeting cysteine residues. • Thiram and ferbam do not inhibit rat 3β-HSD4. [ABSTRACT FROM AUTHOR]