Convergent evidence links traditional brominated flame retardants (BFRs) exposure to weight gain, while the obesogenic potency of new BFRs (NBFRs) remain largely unknown. Aiding by ...luciferase-reporter gene assay, the present study revealed only pentabromoethylbenzene (PBEB), an alternative for penta-BDEs, binds with retinoid X receptor α (RXRα) but not peroxisomeproliferator receptor γ (PPARγ) among the seven testing NBFRs. An apparent induction of adipogenesis in 3T3-L1 cells was observed at nanomolar of PBEB, much lower than penta-BFRs. Mechanistic research uncovered PBEB initiated the adipogenesis by demethylated CpG sites in the PPARγ promoter region. Specifically, activation RXRα by PBEB strengthened the activity of RXRα/PPARγ heterodimer, tightened the interaction between the heterodimer and PPAR response elements, and further enhanced adipogenesis. RNA sequencing combined with k-means clustering analysis exposed adenosine 5′-monophosphate (AMP)-activated protein kinase and phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling as two predominant pathways that enriched in PBEB-induced lipogenesis. The obesogenic outcome was further corroborated in offspring mice when the maternal mice exposed to environmental relevant doses of PBEB. We found the male offspring exhibited adipocyte hypertrophy and increased weight gain in the epididymal white adipose tissue (eWAT). Consistent with in vitro findings, the reduction in protein phosphorylation of both AMPK and PI3K/AKT were observed within eWAT. Thus, we posited PBEB disrupts the pathways controlling adipogenesis and adipose tissue maintenance, supporting its potential as an environmental obesogen.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Improving the performance of professional cyclists during individual time trials has been a challenge for several decades. In this study, the fatigue power profiles of male and female ...professional cyclists were characterized and a novel optimal pacing strategy model was established to determine the output power distribution based on the simulated annealing algorithm. Moreover, the model was implemented on the male 2021 UCI ITT course and the female 2021 Olympic ITT course. Compared with the actual performance of the professional cyclists, the race scores predicted by this model are among the best, which indicates that the model is highly practical and instructive. Considering riders are unlikely to follow the detailed plan exactly and their output power can deviate from the optimal power, a sensitivity analysis was conducted and the results demonstrated the high stability and reliability of the model.
The worldwide prevalence of obesity highlights the potential contribution of endocrine-disrupting chemicals (EDCs). However, common epidemiological measures such as body mass index and waist ...circumference may misrepresent the intricate obesity risks these chemicals pose across genders. This study delves deeper into abdominal fat by differentiating between subcutaneous and visceral regions by analyzing data from National Health and Nutrition Examination Surveys (NHANES). We particularly investigated the gender-specific associations between organophosphorus flame-retardant metabolites (mOPFRs), phthalates (mPAEs) and accumulated fat indexes from 2536 people. Aiding by Bayesian Kernel Machine Regression (BKMR), we found while co-exposure to mOPFRs and mPAEs was linked to general and abdominal obesity across the entire and gender-specific populations, a gender-specific fat distribution emerged. For women, urinary BDCPP and MBzP were linked to an increased subcutaneous fat index (SFI) BDCPP OR: 1.12 (95% CI: 1.03–1.21), MBzP OR: 1.09 (95% CI: 1.01–1.18), but not to visceral fat index (VFI). These metabolites had a combined linkage with SFI, with BDCPP (weighting 22.0%) and DPHP (weighting 31.0%) being the most influential in Quantile g-computation model (qgcomp) model. In men, BCEP exposure exclusively associated with the elevated VFI OR: 1.14 (95% CI: 1.03–1.26), a trend further highlighted in mixture models with BCEP as the predominant association. Intriguingly, only males displayed a marked correlation between these metabolites and insulin resistance in subpopulation. An attempted mediation analysis revealed that elevated C-reactive protein mediated 12.1% of the association between urinary BCEP and insulin resistance, suggesting a potential role of inflammation. In conclusion, the gender-specific fat distribution and insulin resistance that associated with mOPFRs represented the potential risk of these chemicals to man.
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•Co-exposure of mOPFRs and mPAEs relates to obesity risk.•The metabolites associate with gender-specific abdominal fat changes.•Certain metabolites correlated with visceral fat indexes and insulin resistance only in men.•Inflammation may mediate BCEP-insulin resistance association.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cynaroside is the primary flavonoid component of honeysuckle which has been widely used as Chinese traditional medicine given its anti-inflammation properties. Overactive systemic inflammatory ...response and multi-organ injury are the leading causes of life-threatening sepsis. Regulation of macrophage polarization balance may act as a promising strategy for its treatment. In the present study, we aimed to investigate whether cynaroside exerted protective effects against sepsis and its potential mechanism. Building upon a sepsis mouse model, we observed cynaroside alleviated serum levels of inflammatory factors including IL-1β and TNF-α at 5 and 10 mg/kg. The pathological injury of heart, kidney and lung was remarkedly attenuated as the levels of blood urea nitrogen, creatinine, creatine kinase-MB and lactate dehydrogenase were reduced nearly 2.8-, 2.7-, 2.4-, and 2.5-fold as compared with the sepsis mice, respectively. We further demonstrated cynaroside suppressed the biomarker of pro-inflammatory macrophage M1 phenotype (iNOS+) and promotes the anti-inflammatory M2 polarization (CD206+) in the injury organs of septic mice. Mechanistic research verified cynaroside inhibited LPS-induced polarization of macrophage into M1 phenotype, which can be highly blocked by Nrf2 inhibitor. Expectedly, Nrf2 and its downstream (Heme oxygenase-1 (HO-1)) was upregulated in injury organs after treating with cynaroside, indicating the involvement of Nrf2 signaling. Taken together, the data claims cynaroside ameliorated systematic inflammation and multi-organ injury dependent on Nrf2/HO-1 pathway in septic mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sandwich structures with good mechanical performance can be manufactured by continuous carbon‐fiber‐reinforced composites (CCFRC) via the fused filament fabrication (FFF) technology. Poor ...inter‐thread bonding is a major reason for the failure of these sandwich structures. In the present study, a novel fiber‐interleaved printing pattern has been proposed to improve the bonding property between printing threads. And panel/core integrated sandwich structures were fabricated via the FFF technology. The manufacturing quality was examined by microscopic examination and non‐destructive computed tomography (CT) scanning. The results indicated that manufacturing voids are mainly concentrated in the printed carbon fiber bundles, resulting from inadequate infiltration between the reinforcement and the matrix. Flatwise compression tests were conducted to compare the mechanical performance of sandwich structures with the fiber‐adjacent and fiber‐interleaved core. The results clearly demonstrated that the fiber‐interleaved design can significantly improve the mechanical performance of the sandwich structures (i.e., 44% higher in elastic modulus and 119% higher in strength). Furthermore, three‐point bending tests were conducted to investigate the flexural behavior. Fractographic analysis demonstrated that the main failure modes under these loading conditions include fiber pull‐out and breakage, delamination, local core crushing, fiber/matrix and panel/core debonding.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The development of lightweight composites with desirable thermo‐mechanical properties is progressively increasing. Phthalonitrile (PN) based composites have shown great potential in this regard. ...However, the basic thermal properties of PN composites required for engineering design are not yet fully understood. In this work, we investigated the thermal stability, thermal expansion behavior and thermal conductivity of PN composites reinforced with carbon fiber (CF) and high silicon fiberglass (HSF) via combined experimental studies and numerical simulations. The results indicated that CF/PN performs better in thermostability than HSF/PN at temperatures below 500°C. Moreover, the incorporation of CF and HSF lowered the coefficient of thermal expansion (CTE) and thermal insulation of PN. At room temperature, the in‐plane CTE of CF/PN and HSF/PN were 1.97E‐6 and 9.24E‐6°C−1, respectively, while the out‐plane thermal conductivities of CF/PN and HSF/PN were 0.65 and 0.34 W/(m K). It is worth noting that an excessively high fiber volume fraction would lead to poor thermal insulation and lightweight properties of the PN composites, while a low fiber volume fraction would result in poor stiffness and thermal dimensional stability. Determined via TOPSIS model, a fiber volume fraction range of 50%–60% was ideal for both composites with comprehensive optimal properties, respectively.
Preparation and simulation of PN composites.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The treatment of sepsis is still challenging and the liver is an important target of sepsis-related injury. Macrophages are important innate immune cells in liver, and modulation of macrophages M1/M2 ...polarization may be a promising strategy for septic liver injury treatment. Macrophage polarization and inflammation of liver tissue has been shown regulated by pyruvate kinase M2 (PKM2)-mediated aerobic glycolysis and immune inflammatory pathways. Therefore, modulating PKM2-mediated immunometabolic reprogramming presents a novel strategy for inflammation-associated diseases. In this study, cynaroside, a flavonoid compound, promoted macrophage phenotypic transition from pro-inflammatory M1 to anti-inflammatory M2, and mitigated sepsis-associated liver inflammatory damage. We established that cynaroside reduced binding of PKM2 to hypoxia-inducible factor-1α (HIF-1α) by abolishing translocation of PKM2 to the nucleus and promoting PKM2 tetramer formation, as well as suppressing phosphorylation of PKM2 at Y105 in vivo and in vitro. Moreover, cynaroside restored pyruvate kinase activity, inhibited glycolysis-related proteins including PFKFB3, HK2 and HIF-1α, and inhibited glycolysis-related hyperacetylation of HMGB1 in septic liver. Therefore, this study reports a novel function of cynaroside in hepatic macrophage polarization, and cecum ligation and puncture-induced liver injury in septic mice. The findings provide crucial information with regard to therapeutic efficacy of cynaroside in the treatment of sepsis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Investigation of the strength, deformation and constitutive model of rocks under true three-dimensional stress is of much significance to scientifically and accurately predict the integrity of ...underground gas storage caprock. In general the intermediate principal stress and the minimum principal stress to which the caprock is subjected are not equal, and there is uncertainty in the in-situ stress test. In this study, the siltstone is taken from the caprock of the Hutubi gas storage in Xinjiang, with a buried depth of 3600 m. A series of true triaxial compression tests on siltstones were carried out using a true triaxial testing system for rocks, and the strength and deformation characteristics of siltstones under different intermediate principal stress conditions were studied. The elastoplastic constitutive model of rocks has been established: in the plastic part, the Mogi-Coulomb yield criterion has been modified so as to obtain the triple-mean-normal-stress yield function and triple-mean-normal-stress potential function suitable for rocks under the true three-dimensional stress state. The hardening law has been determined by fitting the relationship between the plastic deviatoric shear strain and the deviatoric stress in the true triaxial compression test. The constitutive model and the test data of siltstones have been verified by fitting. Finally, the influence of true triaxial stress on the permeability and breakthrough pressure of caprock siltstones has been discussed. The result indicates that with the increase of intermediate principal stress within a certain range, the peak strength of siltstones will also increase, and deformation in the direction of the intermediate principal stress will be restrained. Compared with the potential functions in other constitutive models, the triple-mean-normal-stress potential function proposed in this paper can accurately describe the plastic flow direction of siltstones under the true three-dimensional stress state. And the hardening law truly reflects the plastic deformation of siltstone specimens under different stress states during the loading process. The calculation result of the constitutive model is in good agreement with the test result. Under the true three-dimensional stress, the permeability of siltstones shows anisotropy. With the increase of the intermediate principal stress, the minimum value of siltstone permeability decreased by 8%, and the maximum value of breakthrough pressure increased by 4.3%.
•The deformation and strength of rocks under the true three-dimensional stress are studied.•The triple-mean-normal-stress potential function proposed can truly describe the plastic flow direction.•A constitutive model emphasis on plastic potential and hardening law of rocks is established and verified.•The anisotropy of rock permeability is confirmed under the true three-dimensional stress.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZRSKP
In this paper, we investigate multiple flexible spacecrafts attitude synchronization with parametric uncertainties and external disturbances. A large number of results on this problem rely on ...accurate measurements, ignoring measurement noises in attitude and angular velocity feedback. However, the existence of inherent noises and accumulated measurement errors are invertible, such that the performance of synchronization may be damaged. By developing a decentralized measurement-based attitude controller, we achieve attitude synchronization having input-to-state stability (ISS) with respect to measurement noises as external input. Moreover, thanks to the ISS-based robust design procedure, each of flexible spacecraft attitude control subsystem gains modeled external disturbance rejection, as well as unmodeled actuator disturbances attenuation and robustness with regarding to uncertain parameters.
There are many articles reporting that the component of intestinal microbiota implies a link to anxiety disorders (AD), and the brain-gut axis is also a hot topic in current research. However, the ...specific relevance between gut microbiota and AD is uncertain. We aimed to investigate causal relationship between gut microbiota and AD by using bidirectional Mendelian randomization (MR).
Genetic instrumental variable (IV) for the gut microbiota were obtained from a genome-wide association study (GWAS) involving 18,340 participants. Summary data for AD were derived from the GWAS and included 158,565 cases and 300,995 controls. We applied the inverse variance weighted (IVW) method as the main analysis. Cochran's Q values was computed to evaluate the heterogeneity among IVs. Sensitivity analyses including intercept of MR-Egger method and MR-PRESSO analysis were used to test the horizontal pleiotropy.
We discovered 9 potential connections between bacterial traits on genus level and AD. Utilizing the IVW method, we identified 5 bacterial genera that exhibited a direct correlation with the risk of AD: genus Eubacteriumbrachygroup, genus Coprococcus3, genus Enterorhabdus, genus Oxalobacter, genus Ruminiclostridium6. Additionally, we found 4 bacterial genera that exhibited a negative association with AD: genus Blautia, genus Butyricicoccus, genus Erysipelotrichaceae-UCG003 and genus Parasutterella. The associations were confirmed by the sensitivity analyses.
Our study found a causal relation between parts of the gut microbiota and AD. Further randomized controlled trials are crucial to elucidate the positive effects of probiotics on AD and their particular protection systems.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
