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Background: The National Health Commission and the other relevant departments in China have initiated testing of the Diagnosis Related Groups (DRGs) system in 30 pilot locations since 2019. In the process of DRG payment reform, accounting for the costs of diseases has become a highly challenging issue. The traditional method of disease accounting method overlooks the compensation for the knowledge capital value of medical personnel. Objective: The primary objective of this study is to analyze the cost accounting scheme of China's Diagnosis Related Groups (C-DRG), focusing on the value of knowledge capital. Methods: The study initially proposes a measurement index system for the value of knowledge-based capital, including the difficulty of disease treatment, labor intensity of disease treatment, risk of disease treatment, and operation/treatment time for diseases. The Analytic Hierarchy Process (AHP) is then utilized to weigh the features of medical workers' knowledge capital value. First, pairwise comparisons are conducted in this stage to develop a two-pair judgment matrix of the primary indicators. Second, the eigenvectors corresponding to the maximum eigenvalues of the matrix are calculated to generate the weight coefficient of each feature. The consistency test is carried out after this stage. An empirical analysis is conducted by collecting data, including the full costs of treating three types of diseases-hip replacement, acute simple appendicitis, and heart bypass surgery-from one public medical institution. Results: The empirical analysis examines whether this DRG costing accounting can address the issue of neglecting the value of medical workers' knowledge capital. The methods reconfigure the positive incentive mechanism, stimulate the endogenous motivation of the medical service system, foster independent changes in medical behavior, and achieve the goals of reasonable cost control. Conclusion: In the cost accounting system of C-DRG, the value of medical workers' knowledge capital is acknowledged. This acknowledgment not only boosts the enthusiasm and creativity of medical workers in optimizing and standardizing the diagnosis and treatment process but also improves the transparency and authenticity of DRG pricing. This is particularly evident in the optimization and standardization of the diagnosis and treatment processes within medical institutions and in monitoring inadequate medical practices within these institutions.
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Grupos Diagnósticos Relacionados , Humanos , China , Grupos Diagnósticos Relacionados/economia , Contabilidade , Custos de Cuidados de Saúde/estatística & dados numéricos , Efeitos Psicossociais da DoençaRESUMO
Developing the films of N-containing unsubstituted poly(p-phenylene) (PPP) films for diverse applications is significant and highly desirable because the replacement of sp2 C atoms with sp2 N atoms will bring novel properties to the as-prepared polymers. In this research, an electrochemical-dehalogenation polymerization strategy is employed to construct two N-containing PPP films under constant potentials, where 2,5-diiodopyridine (DIPy) and 2,5-dibromopyrazine (DBPz) are used as starting agents. The corresponding polymers are named CityU-23 (for polypyridine) and CityU-24 (for polypyrazine). Moreover, it is found that both polymers can form films in situ on different conductive substrates (i.e., silicon, gold, ITO, and nickel), satisfying potential device fabrication. Furthermore, the as-obtained thin films of CityU-23 and CityU-24 exhibit good performance of alkaline hydrogen evolution reaction with the overpotential of 212.8 and 180.7 mV and the Tafel slope of 157.0 and 122.4 mV dec-1, respectively.
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Pristine iron triad metal-organic frameworks (MOFs), i.e., Fe-MOFs, Co-MOFs, Ni-MOFs, and heterometallic iron triad MOFs, are utilized as versatile and promising cathodes for alkali metal-ion batteries, owing to their distinctive structure characteristics, including modifiable and designable composition, multi-electron redox-active sites, exceptional porosity, and stable construction facilitating rapid ion diffusion. Notably, pristine iron triad MOFs cathodes have recently achieved significant milestones in electrochemical energy storage due to their exceptional electrochemical properties. Here, the recent advances in pristine iron triad MOFs cathodes for alkali metal-ion batteries are summarized. The redox reaction mechanisms and essential strategies to boost the electrochemical behaviors in associated electrochemical energy storage devices are also explored. Furthermore, insights into the future prospects related to pristine iron triad MOFs cathodes for lithium-ion, sodium-ion, and potassium-ion batteries are also delivered.
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Helical morphologies are widely observed in nature, however, it is very challenging to prepare artificial helical polymers. Especially, precisely understanding the structure information of artificial metal-free helical covalent inorganic polymers via single-crystal X-ray diffraction (SCXRD) analysis is rarely explored. Here, we successfully prepare a novel metal-free helical covalent inorganic polymer ({[Te(C6 H5 )2 ] [PO3 (OH)]}n , named CityU-10) by introducing angular anions (HOPO3 2- ) into traditional tellurium-oxygen chains. The dynamic reversibility of the reaction is realized through the introduction of organic tellurium precursor and the slow hydrolysis of polyphosphoric acid. High-quality and large-size single crystals of CityU-10 have been successfully characterized via SCXRD, where the same-handed helical inorganic polymer chains form a pseudo-two-dimensional layer via multiple hydrogen-bonding interactions. The left-handed layers and right-handed layers alternatively stack together through weak hydrogen bonds to form a three-dimensional supramolecular structure. The single crystals of CityU-10 are found to display promising optical properties with a large birefringence. Our results would offer new guidelines for designing and preparing new crystalline covalent polymers through tellurium-based chemistry.
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Cognitive dysfunction increases as menopause progresses. We previously found that estrogen receptors (ERs) contribute to dyslipidemia, but the specific relationship between ERs, dyslipidemia and cognitive dysfunction remains poorly understood. In the present study, we analyzed sequencing data from female hippocampus and normal breast aspirate samples from normal and Alzheimer's disease (AD) women, and the results suggest that abnormal ERs signaling is associated with dyslipidemia and cognitive dysfunction. We replicated a mouse model of dyslipidemia and postmenopausal status in LDLR-/- mice and treated them with ß-estradiol or simvastatin, and found that ovariectomy in LDLR-/- mice led to an exacerbation of dyslipidemia and increased hippocampal apoptosis and cognitive impairment, which were associated with reduced estradiol levels and ERα, ERß and GPER expression. In vitro, a lipid overload model of SH-SY-5Y cells was established and treated with inhibitors of ERs. ß-estradiol or simvastatin effectively attenuated dyslipidemia-induced neuronal apoptosis via upregulation of ERs, whereas ERα, ERß and GPER inhibitors together abolished the protective effect of simvastatin on lipid-induced neuronal apoptosis. We conclude that decreased estrogen and its receptor function in the postmenopausal stage promote neuronal damage and cognitive impairment by exacerbating dyslipidemia, and that estrogen supplementation or lipid lowering is an effective way to ameliorate hippocampal damage and cognitive dysfunction via upregulation of ERs.
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Disfunção Cognitiva , Receptor alfa de Estrogênio , Humanos , Camundongos , Feminino , Animais , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Pós-Menopausa , Estrogênios/farmacologia , Estradiol/farmacologia , Disfunção Cognitiva/complicações , Sinvastatina/farmacologia , Sinvastatina/uso terapêutico , LipídeosRESUMO
The development of lithium (Li) metal batteries (LMBs) has been limited by problems, such as severe dendrite growth, drastic interfacial reactions, and large volume change. Herein, an LMB (8AP@LiB) combining agraphene oxide-poly(ethylene oxide) (PEO) functionalized polypropylene separator (8AP) with a lithium-boron (LiB) anode is designed to overcome these problems. Raman results demonstrate that the PEO chain on 8AP can influence the Li+ solvation structure in the electrolyte, resulting in Li+ homogeneous diffusion and Li+ deposition barrier reduction. 8AP exhibits good ionic conductivity (4.9 × 10-4 S cm-1), a high Li+ migration number (0.88), and a significant electrolyte uptake (293%). The 3D LiB skeleton can significantly reduce the anode volume changes and local current density during the charging/discharging process. Therefore, 8AP@LiB effectively regulates the Li+ flux and promotes the uniform Li deposition without dendrites. The Li||Li symmetrical cells of 8AP@LiB exhibit a high electrochemical stability of up to 1000 h at 1 mA cm-2 and 5 mAh cm-2. Importantly, the Li||LiFePO4 full cells of 8AP@LiB achieve an impressive 2000 cycles at 2C, while maintaining a high-capacity retention of 86%. The synergistic effect of the functionalized separator and LiB anode might provide a direction for the development of high-performance LMBs.
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Acute cardiovascular events increase significantly in postmenopausal women. The relationship between estrogen receptor (ER) and plaque stability in the postmenopausal stage remains to be elucidated. We aimed to explore whether ERα activation improves plaque instability in the postmenopausal stage. Here, we report that postmenopausal women showed increased macrophage activation and plaque instability with increased MCP-1, MMP9, TLR4, MYD88 and NF-κB p65 and decreased ERα and TIMP1 expression in the vascular endothelium. Moreover, ovariectomy in LDLR-/- mice resulted in a significant increase in plaque area and necrotic core area, as well as a significant decrease in collagen content and an increase in macrophage accumulation in the artery. Ovariectomy also reduced serum estrogen levels and ERα expression and upregulated TLR4 and MMP9 expression in arteries in LDLR-/- mice. Estrogen or phytoestrogen therapy upregulated the expression level of ERα in ovariectomized mice and increased plaque stability by inhibiting macrophage accumulation and TLR4 signaling. In vitro, LPS incubation of RAW264.7 cells resulted in a significant decrease in ERα and TIMP1 expression and an increase in TLR4 activation, and estrogen or phytoestrogen treatment increased ERα and TIMP1 expression and inhibited TLR4 activation and MMP9 expression in LPS-treated RAW264.7 cells. Compared to control siRNA transfected RAW264.7 cells, TLR4 siRNA promoted TIMP1 expression in RAW264.7 cells with LPS incubation, but did not affect ERα expression in RAW264.7 cells with or without LPS treatment. The ERα inhibitor MPP abolished the regulatory effect of estrogen or phytoestrogen on LPS-induced RAW264.7 cells. In conclusion, the present study demonstrates that decreased ERα expression promotes macrophage infiltration and plaque instability in the postmenopausal stage, and activation of ERα in the postmenopausal stage alleviates atherosclerotic plaque instability by inhibiting TLR4 signaling and macrophage-related inflammation.
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Receptor alfa de Estrogênio , Placa Aterosclerótica , Receptor 4 Toll-Like , Animais , Feminino , Camundongos , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Lipopolissacarídeos , Macrófagos , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , NF-kappa B/metabolismo , Fitoestrógenos , Pós-Menopausa , RNA Interferente Pequeno/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Humanos , Células RAW 264.7RESUMO
Carbon-coated metal chalcogenide composites have been demonstrated as one type of promising anode material for sodium-ion batteries (SIBs). However, combining carbon materials with micronanoparticles of metal chalcogenide always involve complicated processes, such as polymer coating, carbonization, and sulfidation/selenization. To address this issue, herein, we reported a series of carbon-coated FexSey@CN (FexSey = FeSe2, Fe3Se4, Fe7Se8) composites prepared via the thermodynamic transformation of a crystalline organic hybrid iron selenide [Fe(phen)2](Se4) (phen = 1,10-phenanthroline). By pyrolyzing the bulk crystals of [Fe(phen)2](Se4) at different temperatures, FexSey microrods were formed in situ, where the nitrogen-doped carbon layers were coated on the surface of the microrods. Moreover, all the as-prepared FexSey@CN composites exhibited excellent sodium-ion storage capabilities as anode materials in SIBs. This work proves that crystalline organic hybrid metal chalcogenides can be used as a novel material system for the in situ formation of carbon-coated metal chalcogenide composites, which could have great potential in the application of electrochemical energy storage.
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Sea buckthorn is rich in polyphenolic compounds with antioxidant activities. However, it is very sour, and its odor is slightly unpleasant, so it requires flavor improvement. Fermentation is one potential method. Sea buckthorn juice was fermented at 37 °C for 72 h and then post-fermented at 4 °C for 10 days. The flavor-related properties of the sea buckthorn juice were evaluated during fermentation, including the pH, total soluble solids (TSS), color, sensory evaluation, and volatile flavors. The sea buckthorn fermented juice had a low pH. The total soluble solids decreased from 10.60 ± 0.10% to 5.60 ± 0.12%. The total color change was not more than 20%. Fermentation increased the sweet odor of the sea buckthorn juice, but the fruity flavor decreased and the bitter flavor increased. A total of 33 volatile flavors were identified by headspace gas chromatography-ion mobility spectrometry (GC-IMS), including 24 esters, 4 alcohols, 4 terpenes, and 1 ketone. Their total relative contents were 79.63-81.67%, 10.04-11.76%, 1.56-1.22%, and 0.25-0.55%, respectively. The differences in the characteristic volatile molecular species of the sea buckthorn juice at different fermentation stages could be visually discerned using fingerprint maps. Through principal component analysis (PCA), the total flavor difference of the sea buckthorn juice at different fermentation stages could be effectively distinguished into three groups: the samples fermented for 0 h and 12 h were in one group, the samples fermented for 36 h, 48 h, 60 h, and 72 h were in another group, and the samples fermented for 24 h were in another group. It is suggested that sea buckthorn juice be fermented for 36 h to improve its flavor. GC-IMS and PCA are effective methods of identifying and distinguishing the flavor characteristics of sea buckthorn juice. The above results can provide a theoretical basis for studying the changes in sea buckthorn's characteristics as a result of fermentation, particularly with regard to its flavor.
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Concerns regarding inevitable soil translocation and bioaccumulation of cadmium (Cd) in plants have been escalating in concomitance with the posed phytotoxicity and threat to human health. Exhibiting a Cd tolerance, Bacillus sp. M6 strain has been reported as a soil amendment owing to its capability of reducing metal bioavailability in soils. The present study investigated the rhizospheric bacterial community of the Cd hyperaccumulator Sedum alfredii using 16S rRNA gene sequencing. Additionally, the Cd removal efficiency of strain Bacillus sp. M6 was enhanced by supplementing with biochar (C), glutamic acid (G), and rhamnolipid (R) to promote the phytoremediation effect of hyperaccumulator S. alfredii. To the best of our knowledge, this is the first time the amendments such as C, G, and R together with the plant-microbe system S. alfredii-Bacillus sp. M6 has been used for Cd bioremediation. The results showed that soil CaCl2 and DTPA (Diethylenetriamine penta-acetic acid) extractable Cd increased by 52.77 and 95.08%, respectively, in all M6 treatments compared to unamended control (CK). Sedum alfredii with Bacillus sp. M6 supplemented with biochar and rhamnolipid displayed a higher phytoremediation effect, and the removal capability of soil Cd (II) reached up to 16.47%. Moreover, remediation of Cd polluted soil by Bacillus sp. M6 also had an impact on the soil microbiome, including ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea (AOA), and cadmium transporting ATPase (cadA) genes. Quantitative PCR analysis confirmed the Bacillus sp. M6 strain increased the abundance of AOB and cadA in both low Cd (LC) and high Cd (HC) soils compared to AOA gene abundance. Besides, the abundance of Proteobacteria and Actinobacteria was found to be highest in both soils representing high tolerance capacity against Cd. While Firmicutes ranked third, indicating that the additionof strain could not make it the most dominant species. The results suggested the presence of the hyperaccumulator S. alfredii and Cd tolerant strain Bacillus sp. M6 supplemented with biochar, and rhamnolipid, play a unique and essential role in the remediation process and reducing the bioavailability of Cd.
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Amelioration of neuroinflammation via modulating microglia is a promising approach for cerebral ischemia therapy. The aim of the present study was to explore gut-brain axis signals in berberine-modulating microglia polarization following cerebral ischemia. The potential pathway was determined through analyzing the activation of the vagus nerve, hydrogen sulfide (H2 S) metabolism, and cysteine persulfides of transient receptor potential vanilloid 1 (TRPV1) receptor. The cerebral microenvironment feature was explored with a metabolomics assay. The data indicated that berberine ameliorated behavioral deficiency in transient middle cerebral artery occlusion rats through modulating microglia polarization and neuroinflammation depending on microbiota. Enhanced vagus nerve activity following berberine treatment was blocked by antibiotic cocktails, capsazepine, or sodium molybdate, respectively. Berberine-induced H2 S production was responsible for vagus nerve stimulation achieved through assimilatory and dissimilatory sulfate reduction with increased synthetic enzymes. Sulfation of the TRPV1 receptor resulted in vagus nerve activation and promoted the c-fos and ChAT in the nucleus tractus solitaries with berberine. Sphingolipid metabolism is the primary metabolic characteristic with berberine in the cerebral cortex, hippocampus, and cerebral spinal fluid disrupted by antibiotics. Berberine, in conclusion, modulates microglia polarization in a microbiota-dependent manner. H2 S stimulates the vagus nerve through TRPV1 is responsible for the berberine-induced gut-brain axis signal transmission. Sphingolipid metabolism might mediate the neuroinflammation amelioration following vagus afferent fiber activation.
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Berberina , Isquemia Encefálica , Sulfeto de Hidrogênio , Microbiota , Animais , Berberina/farmacologia , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Microglia/metabolismo , Ratos , Esfingolipídeos/metabolismo , Nervo Vago/metabolismoRESUMO
Triptolide exhibits superior and broad-spectrum antitumor activity. However, the narrow safety window caused by the toxicity of triptolide limits its clinical applications. Although several characterized targets for triptolide are reported, the association between triptolide and its targets in cancer therapy is not fully understood. Here, we show that acute myeloid leukemia (AML) cell lines are sensitive to triptolide by constructing an in vitro cell and in vivo xenograft models. Meanwhile, the triptolide-induced hepatotoxicity increases with increasing dosages within the xenograft models. Additionally, the expression levels of WSTF-RPB1 are strongly associated with the sensitivity to triptolide in hematological cancer cells and can be downregulated in a dose and time-dependent manner. Finally, we show that optimizing dosing regimens can achieve the same pharmaceutical effect and reduce toxicity. In summary, this study aims to search for triptolide-sensitive cell lines as well as the underlying molecular mechanisms in order to broaden the safety window of triptolide; thus, increasing its clinical utility.
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BACKGROUND: Serious mental illness is a disease with complex etiological factors that requires multiple interventions within a holistic disease system. With heat-clearing and detoxifying effects, Coptis chinensis Franch. is mainly used to treat serious mental illness. AIM OF THE STUDY: To explore the underlying mechanisms and therapeutic effect by which Coptis chinensis Franch. treats serious mental illnesses at a holistic level. METHODS: A viable network pharmacology approach was adopted to obtain the potential active ingredients of Coptis chinensis Franch., and serious mental illnesses-related targets and signaling pathways. The interactions between crucial target HTR2A and constituents were verified by molecular docking, and the dynamic behaviors of binding were studied by molecular dynamics simulation. In addition, the anti-anxiety effect of Rhizoma Coptidis (the roots of Coptis chinensis Franch.) extract on lipopolysaccharide-stimulated mice was verified. The anxiety-like behavior was measured through the elevated plus-maze test, light-dark box test, and open field test. Radioimmunoassays detected the levels of interleukin-1ß, tumor necrosis factor-α, interleukin-10, interleukin-4, 5-hydroxytryptamine, and dopamine in the serum, hippocampus, medial prefrontal cortex, and amygdala. Meanwhile, immunohistochemistry protocols for the assessment of neuronal loss (neuron-specific nuclear protein) and synaptic alterations (Synapsin I) were performed in the hippocampus. RESULTS: Based on scientific analysis of the established networks, serious mental illnesses-related targets mostly participated in the calcium signaling pathway, cyclic adenosine monophosphate signaling pathway, mitogen-activated protein kinase signaling pathway, serotonergic and dopaminergic synapse. Molecular docking and molecular dynamics simulation studies illustrated that berberine, epiberberine, palmatine, and coptisine presented favorable binding patterns with HTR2A. The in vivo experiments confirmed that Rhizoma Coptidis extract ameliorated anxiety-like behaviors by improving the survival of neurons, regulating synaptic plasticity, and inhibiting neuroinflammation. CONCLUSION: These findings in the present study led to potential preventative and therapeutic strategies for serious mental illnesses with traditional Chinese medicine.
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Coptis , Medicamentos de Ervas Chinesas , Transtornos Mentais , Animais , Coptis/química , Coptis chinensis , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Farmacologia em RedeRESUMO
Engineering the heterogeneous interface fusing MOFs and inorganic active component is an effective strategy to improve the electrochemical performance. Herein, we report a new Ni3-based MOF (denoted as CTGU-24) with an infrequent two-fold interpenetrating 3D (3,8)-connected network constructed from Ni(II) trimer and mixed tripodal tectonics for the electrocatalytic methanol oxidation reaction (MOR). In order to improve its stability and activities, the heterogeneous hybrid CTGU-24@NiOOH has been fabricated successfully via the first preparation of the NiOOH nanosphere and then in situ formation of CTGU-24 decorated on the NiOOH surface. Moreover, the integration of CTGU-24@NiOOH and different additives [acetylene black (AB) and ketjen black (KB)], resulting in the optimized hybrid sample AB&CTGU-24@NiOOH (4:4). It attains better MOR performance with an area-specific peak current density of 34.53 mA·cm-2 than pure CTGU-24 (14.99 mA·cm-2) and improved durability in an alkali medium. The new findings indicate that the CTGU-24@NiOOH heterostructure formed in situ and the integration of moderate additives are critical to optimizing and improving electrocatalytic activity of pure MOF crystalline material.
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Atherosclerosis (AS) is exacerbated in the perimenopausal period, which significantly increases the incidence rate of cardiovascular disease. The disruption of the gut microbiota has been associated with AS or menopause, but the specific changes of AS-associated gut microbiota in the perimenopausal period remain largely unknown. As lipid abnormalities are mainly responsible for AS, the relationship between lipid metabolism abnormalities and gut microbiota disruptions during menopause is rarely reported hitherto. In the present study, ApoE-/- mice fed with a high-fat diet (HFD) were subjected to ovariectomy and supplemented with estrogen. The ovariectomized HFD-fed ApoE-/- mice underwent significant AS damage, hepatic lipid damage, hyperlipidemia, and changes of lipid metabolism- and transport-related enzymes. There was significantly higher abundance of some lipid metabolites in the plasma of ovariectomized HFD-fed ApoE-/- mice than in non-ovariectomized ones, including cholesterol esters, triglycerides, phospholipids, and other types of lipids (free fatty acids, acylcarnitine, sphingomyelins, and ceramides). The administration of estrogen significantly reduced the contents of most lipid metabolites. The diversity and composition of gut microbiota evidently changed in ovariectomized HFD-fed ApoE-/- mice, compared to HFD-fed ApoE-/- mice without ovariectomy. In contrast, with estrogen supplementation, the diversity and composition of gut microbiota were restored to approach that of non-ovariectomized HFD-fed ApoE-/- mice, and the relative abundances of some bacteria were even like those of C57BL/6 mice fed with a normal diet. On the other hand, the transplantation of feces from C57BL/6 mice fed with normal diet to ovariectomized HFD-fed ApoE-/- mice was sufficient to correct the hyperlipidemia and AS damage, and to reverse the characteristics changing of lipid metabolomics in ovariectomized HFD-fed ApoE-/- mice. These phenomena were also been observed after transplantation of feces from estrogen-treated ovariectomized HFD-fed ApoE-/- mice to ovariectomized HFD-fed ApoE-/- mice. Moreover, the gut microbiota and lipid metabolites were significantly correlated, demonstrating that the changes of serum lipids may be associated with the gut microbiota disruptions in the perimenopausal period. In conclusion, the gut microbiota during the progression of AS in the perimenopausal period showed specific compositional changes and significant correlations with circulating lipid metabolites. Estrogen supplementation may exert beneficial effects on gut bacteria and lipid metabolism.
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Aterosclerose/microbiologia , Aterosclerose/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Metabolismo dos Lipídeos , Perimenopausa , Animais , Bactérias/crescimento & desenvolvimento , Dieta Hiperlipídica , Progressão da Doença , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios , Transplante de Microbiota Fecal , Fezes/microbiologia , Feminino , Lipídeos/sangue , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , OvariectomiaRESUMO
Grassland soils serve as a biological sink and source of the potent greenhouse gases (GHG) methane (CH4) and nitrous oxide (N2O). The underlying mechanisms responsible for those GHG emissions, specifically, the relationships between methane- and ammonia-oxidizing microorganisms in grazed grassland soils are still poorly understood. Here, we characterized the effects of grazing on in situ GHG emissions and elucidated the putative relations between the active microbes involving in methane oxidation and nitrification activity in grassland soils. Grazing significantly decreases CH4 uptake while it increases N2O emissions basing on 14-month in situ measurement. DNA-based stable isotope probing (SIP) incubation experiment shows that grazing decreases both methane oxidation and nitrification processes and decreases the diversity of active methanotrophs and nitrifiers, and subsequently weakens the putative competition between active methanotrophs and nitrifiers in grassland soils. These results constitute a major advance in our understanding of putative relationships between methane- and ammonia-oxidizing microorganisms and subsequent effects on nitrification and methane oxidation, which contribute to a better prediction and modeling of future balance of GHG emissions and active microbial communities in grazed grassland ecosystems.
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Excessive inflammation and the pyroptosis of vascular endothelial cells caused by estrogen deficiency is one cause of atherosclerosis in post-menopausal women. Because autophagy is highly regulated by estrogen, we hypothesized that estrogen can reduce vascular endothelial cell pyroptosis through estrogen receptor alpha (ERα)-mediated activation of autophagy to improve atherosclerosis in post-menopausal stage. Aortic samples from pro-menopausal and post-menopausal women with ascending aortic arteriosclerosis were analyzed, and bilateral ovariectomized (OVX) female ApoE-/- mice and homocysteine (Hcy)-treated HUVECs were used to analyze the effect of estrogen supplementation therapy. The aortic endothelium showed a decrease in ERα expression and autophagy, but presented an increase in inflammation and pyroptosis in female post-menopausal patients. Estrogen treatment accelerated autophagy and ameliorated cell pyroptosis in the cardiac aortas of OVX ApoE-/- mice and Hcy-treated HUVECs. Estrogen had therapeutic effect on atherosclerosis and improved the symptoms associated with lipid metabolism disorders in OVX ApoE-/- mice. Inhibition and silencing of ERα led to a reduction in the autophagy promoting ability of estrogen and aggravated pyroptosis. Moreover, the inhibition of autophagy promoted pyroptosis and abolished the protective effect of estrogen, but had no influence on ERα expression. Thus, the results of the present study demonstrated that post-menopausal women present decreased autophagy and ERα expression and excessive damage to the ascending aorta. In addition, in vitro and in vivo assay results demonstrated that estrogen prevents atherosclerosis by upregulating ERα expression and subsequently induces autophagy to reduce inflammation and pyroptosis.
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Decreases in estrogen secretion and estrogen receptor function lead to an increase in the incidence of dyslipidemia and cardiovascular disease (CVD) in postmenopausal women. We previously reported that ß-estradiol has a significant regulatory effect on lipids in ApoE-/- mice with bilateral ovariectomy. In the present study, we investigated how ß-estradiol regulates intestinal function via estrogen receptors to alleviate postmenopausal dyslipidemia. Ovariectomized ApoE-/- mice were treated with ß-estradiol for 90 days, and we found that ß-estradiol reduced TC, TG, LDL-c, IL-1ß and IL-18 levels in serum and decreased lipid accumulation in the liver. ß-estradiol reduced injury and inflammation in the jejunum in ovariectomized mice, and promoted the expression of tight junction-related proteins. Moreover, ß-estradiol increased ERα, ERß, GPR30 and ABCG5 protein expression, and decreased the levels of NPC1L1 and SR-B1 in the jejunum of ovariectomized mice. In Caco-2 cells incubated with cholesterol, ß-estradiol up-regulated PI3K/AKT signaling, reduced cholesterol accumulation, suppressed inflammatory signaling, and increased the expression of tight junction-related proteins. ERß or GPR30 inhibition decreased the protective effect of ß-estradiol on cholesterol accumulation, tight junctions, and inflammation in cholesterol incubated Caco-2 cells, while silencing both ERß and GPR30 completely eliminated the protective effect of ß-estradiol. PI3K/AKT inhibition abolished the protective effect of ß-estradiol on cholesterol accumulation, tight junction-related protein expression, and inflammation, but had no influence on ERα, ERß or GPR30 expression in cholesterol incubated Caco-2 cells. Our results provide evidence that ß-estradiol regulates intestinal function via ERß and GPR30 mediated PI3K/AKT signaling activation to alleviate postmenopausal dyslipidemia.
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Dislipidemias/tratamento farmacológico , Estradiol/farmacologia , Receptor beta de Estrogênio/metabolismo , Estrogênios/farmacologia , Jejuno/efeitos dos fármacos , Pós-Menopausa/metabolismo , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Apolipoproteínas E/genética , Células CACO-2 , Dislipidemias/sangue , Dislipidemias/metabolismo , Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Feminino , Humanos , Jejuno/metabolismo , Lipídeos/sangue , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Ovariectomia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
Pulmonary fibrosis (PF) is a kind of interstitial lung disease with the features of progressive and often fatal dyspnea. Tetrandrine (TET) is the major active constituent of Chinese herbal Stephania tetrandra S. Moore, which has already applied clinically to treat rheumatism, lung cancer, and silicosis. In this work, a tetrandrine-hydroxypropyl-ß-cyclodextrin inclusion compound (TET-HP-ß-CD) was developed for the treatment of pulmonary fibrosis via inhalation administration. TET-HP-ß-CD was prepared by the freeze-drying method and identified using the cascade impactor, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectrum (FT-IR). A bleomycin-induced pulmonary fibrosis rat model was used to assess the effects of inhaled TET and TET-HP-ß-CD. Animal survival, hydroxyproline content in the lungs, and lung histology were detected. The results showed that inhalation of TET-HP-ß-CD alleviated inflammation and fibrosis, limited the accumulation of hydroxyproline in the lungs, regulated protein expression in PF development, and improved postoperative survival. Moreover, nebulized delivery of TET-HP-ß-CD accumulated chiefly in the lungs and limited systemic distribution compared with intravenous administration. The present results indicated that inhalation of TET-HP-ß-CD is an attractive candidate for the treatment of pulmonary fibrosis.