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The metalloid arsenic, known for its toxic properties, is widespread presence in the environment. Our previous research has confirmed that prolonged exposure to arsenic can lead to liver fibrosis injury in rats, while the precise pathogenic mechanism still requires further investigation. In the past few years, the Nod-like receptor protein 3 (NLRP3) inflammasome has been found to play a pivotal role in the occurrence and development of liver injury. In this study, we administered varying doses of sodium arsenite (NaAsO 2) and 10 mg/kg.bw MCC950 (a particular tiny molecular inhibitor targeting NLRP3) to Sprague-Dawley (SD) rats for 36 weeks to explore the involvement of NLRP3 inflammasome in NaAsO 2 -induced liver injury. The findings suggested that prolonged exposure to NaAsO 2 resulted in pyroptosis in liver tissue of SD rats, accompanied by the fibrotic injury, extracellular matrix (ECM) deposition and liver dysfunction. Moreover, long-term NaAsO 2 exposure activated NLRP3 inflammasome, leading to the release of pro-inflammatory cytokines in liver tissue. After treatment with MCC950, the induction of NLRP3-mediated pyroptosis and release of pro-inflammatory cytokines were significantly attenuated, leading to a decrease in the severity of liver fibrosis and an improvement in liver function. To summarize, those results clearly indicate that hepatic fibrosis and liver dysfunction induced by NaAsO 2 occur through the activation of NLRP3 inflammasome-mediated pyroptosis, shedding new light on the potential mechanisms underlying arsenic-induced liver damage. [Display omitted] • Prolonged exposure to arsenite triggered pyroptosis in the liver cells of rats. • Prolonged exposure to arsenite caused fibrotic changes and dysfunction in the liver of rats. • The NLRP3 inflammasome in liver tissue of rats was activated upon prolonged exposure to arsenite. • MCC950 alleviated arsenite-induced pyroptosis in liver cells, ameliorated liver fibrosis and dysfunction in rats. [ABSTRACT FROM AUTHOR]

Arsenic is a well known environmental hazardous material, chronic arsenic exposure results in different types of liver damage. Among them, liver fibrosis has become a research hotspot because of its reversibility, while the underlying mechanism is still unclear. Previous studies revealed that EGFR/ERK signaling appears to play an important role in fibrosis diseases. In this study, sprague-dawley rats were exposed to different doses of arsenite for 36 weeks to investigate the roles of EGFR/ERK signaling on arsenite-induced liver fibrogenesis. Our results showed that long-term arsenite exposure induced liver fibrosis, accompanied by hepatic stellate cells (HSCs) activation, excessive serum secretion of extracellular matrix (ECM), and hepatocytes epithelial-mesenchymal transformation (EMT). In addition, arsenite exposure caused hyperphosphorylation of EGFR/ERK signaling in liver tissue of rats, indicating that EGFR/ERK signaling may be involved in arsenite-induced liver fibrosis. Indeed, erlotinib (a specific phosphorylation inhibitor of EGFR) intervention significantly decreased arsenite induced hyperphosphorylation of EGFR/ERK signaling, thereby suppressed hepatocytes EMT process and alleviated liver fibrogenesis in arsenite exposed rats. In summary, the present study provides evidences showing that hyperphosphorylation of EGFR/ERK signaling facilitates long-term arsenite-induced hepatocytes EMT and liver fibrosis in rats, which brings new insights into the pathogenesis of arsenic-induced liver injury. [Display omitted] • Long-term arsenite exposure induces liver fibrosis in rats. • Arsenite exposure causes hyperphosphorylation of EGFR/ERK signaling in liver tissue of rats. • Hyperphosphorylation of EGFR/ERK signaling promotes arsenite-induced hepatocytes EMT in liver tissue of rats. • Erlotinib attenuates arsenite-induced hepatocytes EMT and liver fibrosis in rats. [ABSTRACT FROM AUTHOR]

Fish morphological colouration is essential for their survival and reproduction success; however, it is vulnerable to environmental factors, such as pollutants. Triphenyltin (TPT) is widespread in aquatic ecosystems, and its impacts on fish have been problematic. Therefore, the purpose of this study was to investigate the effects of TPT at environment-related concentrations (0, 1, 10 and 100 ng Sn/L) on morphological colouration in male guppies (Poecilia reticulata). The results showed that TPT exposure affected both orange/red and dark morphological colouration in guppies. The faded orange/red colouration might be related to the decrease of coloured pteridine and Pts (6-Pyruvoyltetrahydropterin Synthase) expression. In addition, TPT exposure induced melanogenesis, however, much melanin was distributed diffusely in the skin and did not seem to form a spot pattern, giving the fish a dull appearance. According to the skin transcriptional profiles, the changes of dark morphological colouration might be related to the changes in genes related to the functions of melanosome components (Gpnmb , Slc45a2 and Tyr), construction (Ap3d1 , Fig4 , Hps3 , Hps5 , Lyst , Rabggta , Txndc5 and Vps33a), and transport (Rab27a). Additionally, genes related to the regulation of melanogenesis (Atrn and Pomc) and system effects (Atox1 , Atp6ap2 , Atp6v1f , Atp6v1h , Rpl24 , Rps19 and Rps20) might also be involved in the molecular mechanisms of abnormal morphological colouration induced by TPT. The present study provides crucial data on the molecular basis of abnormal morphological colouration in fish exposed to TPT and underscores the importance of toxicological studies of the effects of pollutants in aquatic environments on fish morphological colouration. • Effects of triphenyltin on morphological colouration in male guppies were investigated. • Skin transcriptional profiles were analyzed to clarify the molecular mechanisms. • Triphenyltin exposure affected both orange/red and dark morphological colouration. • Mechanisms of melanosome, melanogenesis, and pteridine synthesis might be involved. [ABSTRACT FROM AUTHOR]

Transcription factors are key determinants of lineage commitment during mammalian development. However, the function and molecular mechanism for the transcription factors in the formation of three primary germ layers during human embryonic development are not fully elucidated. Here, we report that homeobox-containing transcription factor HESX1 plays a critical role in mesendodermal (ME) commitment of human embryonic stem cells (hESCs). Our results show that expression of HESX1 in hESCs is regulated by OCT4 and NANOG, and that its expression level changes with hESC differentiation. We find that knockdown of HESX1 does not disrupt the undifferentiated state of hESCs, in terms of cell morphology and expression levels of pluripotency-associated genes. However, HESX1 deficiency in hESCs impairs their ME commitment, whereas forced expression of HESX1 significantly enhances ME marker expression during ME commitment. Interestingly, HESX1 knockdown in hESCs represses ERK1/2 signaling activated by ME induction, while overexpression of HESX1 markedly enhances ERK1/2 activity during ME commitment of hESCs. Of note, MEK inhibitor PD0325901 weakens or even eliminates HESX1 overexpression-mediated promotive effects on ME induction in a dosage-dependent manner. Together, this study identifies a novel role of HESX1 in hESC commitment to ME cells and establishes the functional link between a transcription factor and lineage-associated signaling. These findings would help to better understand early human development and develop more efficient protocols to induce hESC differentiation to desired lineages. • Expression of HESX1 in hESCs is regulated by OCT4 and NANOG. • HESX1 deficiency impairs induction of mesendodermal (ME) transcription program of hESCs. • HESX1 overexpression (OE) enhances ME commitment of hESCs. • HESX1 modulates ERK1/2 signaling during hESC commitment to ME cells. • ERK1/2 signaling inhibition abrogates the enhancement of HESX1 OE on ME induction. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel eye-sensitive Ba 3 Nb 2 O 2 F 12 (H 2 O) 2 :Tb3+/Mn4+ were synthesized by simple co-precipitation strategy. • Red phosphor presents extremely strong ZPL at ∼ 625 nm and high color purity. • Red and green phosphors exhibit inherently outstanding thermal stability and moisture resistance. • Red and green phosphors coated directly on UV chip can achieve white emission. • The fabricated WLED devices show excellent electroluminescent properties. Novel eye-sensitive Ba 3 Nb 2 O 2 F 12 (H 2 O) 2 :Tb3+ green and Ba 3 Nb 2 O 2 F 12 (H 2 O) 2 :Mn4+ red oxyfluoride phosphors with extremely strong absorption in the UV region were designed and synthesized by simple co-precipitation strategy. Particularly, Tb3+ ions were doped in this matrix for the first time, which greatly improves their absorption efficiency in the near ultraviolet region (367 nm) and emits sharp green light (544 nm). In addition, the Ba 3 Nb 2 O 2 F 12 (H 2 O) 2 :Mn4+ red phosphors have strong zero phonon line (ZPL) emission at 625 nm, which is conducive to improving the sensitivity of human eye and color purity. Meanwhile, the optical properties of the red phosphor are significantly enhanced via doping K+ cations as charge compensators. Crystal field environment and nephelauxetic effect of the as-prepared phosphors before and after K+ cation doping were systematically analyzed. Moreover, these synthesized red/green phosphors have good thermal stability and moisture resistance. Remarkably, the as-prepared Ba 3 Nb 2 O 2 F 12 (H 2 O) 2 :5%Mn4+ or K 0.9 Ba 2.1 Nb 2 O 2 F 12 (H 2 O) 2 :5%Mn4+ red phosphors can be directly mixed with the as-synthesized Ba 3 Nb 2 O 2 F 12 (H 2 O) 2 :13%Tb3+ green phosphor coating on 365 nm near-ultraviolet LED chip to package WLED devices with excellent electroluminescence performance. These findings are conducive to opening an avenue for screening the unique structure of optical materials. [ABSTRACT FROM AUTHOR]

[Display omitted] Fine-tuning the surface structure of transition metal oxides at the atomic level is a promising way to improve the catalytic properties of materials. However, the influence of crystal surface structure on electrode reaction kinetics is still limited. In this study, we propose an in-situ synthesis strategy to obtain two-dimensional carbon/cerium oxide core–shell nanosheets by thermal decomposition of Ce-MOF nanosheets grown on the surface of carbon nanostructures, and fine-tuning the surface structure by introducing oxygen vacancies through defect engineering during the oxide nucleation process is conducted to obtain controllable exposed {1 1 1} and {1 1 0} surface CeO 2 @C composites. Both experiments and theoretical calculations show that the {1 1 0} -dominated nanocomplex (CeO 2 @C-350S) has better kinetic behavior and catalytic activity due to its abundant surface defects, which is manifested in higher active surface area, richer carrier concentration, and better promotion of diffusion and adsorption. In addition, CeO 2 @C-350S electrode has an extremely wide linear range and good stability in the electrochemical detection of nitrite. After 1000 times of the accelerated cycle experiments, CeO 2 @C-350S electrode still maintains 79.3 % of its initial current response, and recovers to 87.3 % after 10 min of stopping the test. The electrode stability is excellent, which is attributed to the clever carbon shell structure of the material. This synthesis strategy can be extended to other carbon-based oxide composite catalysts to improve the electrocatalytic performance and overall stability by adjusting the surface structure. [ABSTRACT FROM AUTHOR]

Human embryonic stem cells (hESCs) can self-renew infinitely and differentiate into the cell types of all lineages of our body, holding great promise for investigating early human embryo development and providing functional cells for disease treatment. For the full application of hESCs, it is necessary to elucidate how hESCs maintain their identity. Recent studies have shown that glycolysis and mitochondrial respiration are linked to pluripotency states. However, the function of mitochondrial respiration in hESCs has not been fully understood. Herein, we report that the adenosine triphosphate (ATP) production rate is comparable between mitochondrial respiration and glycolysis, suggesting an important contribution of mitochondrial respiration to ATP production in conventionally cultured hESCs. To investigate the function of mitochondrial respiration, we silence OGDH expression in hESCs by the inducible CRISPRi method, and find that OGDH knockdown (KD) results in disrupted TCA (tricarboxylic acid) cycle, and diminished mitochondrial respiration activity and total ATP level. Moreover, OGDH KD leads to hESC death and aberrant transcriptional program. Interestingly, blockage of the electron transport chain (ETC) by small molecule inhibitors gives rise to the phenotype similar to that observed in OGDH deficient hESCs. Therefore, genetic and pharmacological perturbations of the mitochondrial respiration impair identity of hESCs. Collectively, our study highlights the pivotal role of the mitochondrial respiration activity for the stemness maintenance of primed hESCs, and unveils OGDH as a key regulator for the proper production of ATP and TCA cycle metabolites in primed hESCs. • Mitochondrial respiration contributes to ATP production in primed hESCs. • Inducible knockdown of OGDH provides a useful model to study TCA cycle. • OGDH deficiency reduces maximal mitochondrial respiration and ATP levels. • OGDH deficiency leads to hESC death and an aberrant transcriptomic profile. • Electron transport chain inhibition causes hESC death and aberrant gene expression. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hollow sphere structure of poly(ionic liquid)s (HPILs) was fabricated as nanoreactor. • HPILs nanoreactor efficiently enhanced the activity of metal catalysts and showed high selectivity of AA. • HPILs could storage and stabilize catalysts during reaction with high activity for 7 times. • HPILs could promote the generation of free radicals to enhance the reaction. • The reaction process of HPILs was theoretically calculated to verify high activity and selectivity. Hollow structure nanoreactors take advantage of catalyst loading and enhanced activity by shell construction. In this work, functionalized poly(ionic liquid)s (PILs) with hollow spherical structures were synthesized by polymerization- and quaternization-based approaches. These hollow structure PILs (HPILs) could be controllable designed from IL monomer easily, giving HPILs various properties. In the subsequent selective oxidation of cyclohexane, the HPILs acting as nanoreactors could efficiently improve the activity of metal salt catalysts (CoCl 2) and displayed adjustable selectivity for cyclohexanone, cyclohexanol (KA) or adipic acid (AA) by different types of HPILs. In kinetic study, it follows first-order reaction kinetics which CoCl 2 /HPIL-C12 had a lower the activation energy of 29.1 kJ/mol. Importantly, these nanoreactors storing the catalysts could be recovered and reused more than 7 times without significant loss of activity. A theoretical model for the hollow spherical reactor was further established to support the advance of the HPILs reactor, which could also help to predict reaction process in other core-shell catalytic system. Due to controlled substrate transfer and enhanced radical generation in HPILs, the reaction process could be adjusted to enhance the conversion of cyclohexane and selective oxidation to AA. [ABSTRACT FROM AUTHOR]

[Display omitted] PTP1B plays an important role as a key negative regulator of tyrosine phosphorylation associated with insulin receptor signaling in the therapy for diabetes and obesity. In this study, the anti-diabetic activity of dianthrone derivatives from Polygonum multiflorum Thunb., as well as the structure–activity relationships, mechanism, and molecular docking were explored. Among these analogs, trans -emodin dianthrone (compound 1) enhances insulin sensitivity by upregulating the insulin signaling pathway in HepG2 cells and displays considerable anti-diabetic activity in db/db mice. By using photoaffinity labeling and mass spectrometry-based proteomics, we discovered that trans -emodin dianthrone (compound 1) may bind to PTP1B allosteric pocket at helix α6/α7, which provides fresh insight into the identification of novel anti-diabetic agents. [ABSTRACT FROM AUTHOR]

[Display omitted] • Six new oligostilbenes obtained from the stems of Caragana sinica. • Natural tetrastilbenes were determined as absolute configuration for the first time. • Obvious inhibition of α -glucosidase in vitro with IC 50 values of 0.1 ∼ 0.4 μ M. • Leachianol (7) showed significant inhibition (88.8%, 10 μ M) of protein tyrosine phosphatase (PTP1B) with IC 50 value of 1.1 μ M in vitro. Six new oligostilbenes, carastilphenols A-E (1 – 5) and (–)-hopeachinol B (6), with three reported oligostilbenes were obtained from the stems of Caragana sinica. The structures of compounds 1 – 6 were determined by comprehensive spectroscopy analysis, and their absolute configurations were determined by electronic circular dichroism calculations. Thus, natural tetrastilbenes were determined as absolute configuration for the first time. Also, we did several pharmacological essays. In the antiviral tests, compounds 2 , 4 and 6 showed moderate anti-coxsackie virus B3 type (CVB3) effect on Vero cells activities in vitro with IC 50 values of 19.2 ∼ 69.3 μ M; and compounds 3 and 4 showed different levels of anti-respiratory syncytial virus (RSV) effect on Hep2 cells activities in vitro with IC 50 values of 23.1 and 33.3 μ M, respectively. As for hypoglycemic activity, compounds 6 – 9 (10 μ M) showed the inhibition of α -glucosidase in vitro with IC 50 values of 0.1 ∼ 0.4 μ M; and compound 7 showed significant inhibition (88.8%, 10 μ M) of protein tyrosine phosphatase 1B (PTP1B) with IC 50 value of 1.1 μ M in vitro. [ABSTRACT FROM AUTHOR]