RESUMO
Biomimetic tactile nervous system (BTNS) inspired by organisms has motivated extensive attention in wearable fields due to its biological similarity, low power consumption, and perception-memory integration. Though many works about planar-shape BTNS are developed, few researches could be found in the field of fibrous BTNS (FBTNS) which is superior in terms of strong flexibility, weavability, and high-density integration. Herein, a FBTNS with multimodal sensibility and memory is proposed, by fusing the fibrous poly lactic acid (PLA)/Ag/MXene/Pt artificial synapse and MXene/EMIMBF4 ionic conductive elastomer. The proposed FBTNS can successfully perceive external stimuli and generate synaptic responses. It also exhibits a short response time (23 ms) and low set power consumption (17 nW). Additionally, the proposed device demonstrates outstanding synaptic plasticity under both mechanical and electrical stimuli, which can simulate the memory function. Simultaneously, the fibrous devices are embedded into textiles to construct tactile arrays, by which biomimetic tactile perception and temporary memory functions are successfully implemented. This work demonstrates the as-prepared FBTNS can generate biomimetic synaptic signals to serve as artificial feeling signals, it is thought that it could offer a fabric electronic unit integrating with perception and memory for Human-Computer interaction, and has great potential to build lightweight and comfortable Brain-Computer interfaces.
Assuntos
Biomimética , Sinapses , Biomimética/métodos , Sinapses/fisiologia , Tato/fisiologia , Memória/fisiologia , Materiais Biomiméticos/química , Humanos , Poliésteres/químicaRESUMO
Cardiorenal syndrome type 4 (CRS4), a progressive deterioration of cardiac function secondary to chronic kidney disease (CKD), is a leading cause of death in patients with CKD. In this study, we aimed to investigate the cardioprotective effect of emodin on CRS4. C57BL/6 mice with 5/6 nephrectomy and HL-1 cells stimulated with 5% CKD mouse serum were used for in vivo and in vitro experiments. To assess the cardioprotective potential of emodin, we employed a comprehensive array of methodologies, including echocardiography, tissue staining, immunofluorescence staining, biochemical detection, flow cytometry, real-time quantitative PCR, and western blot analysis. Our results showed that emodin exerted protective effects on the function and structure of the residual kidney. Emodin also reduced pathologic changes in the cardiac morphology and function of these mice. These effects may have been related to emodin-mediated suppression of reactive oxygen species production, reduction of mitochondrial oxidative damage, and increase of oxidative metabolism via restoration of PGC1α expression and that of its target genes. In contrast, inhibition of PGC1α expression significantly reversed emodin-mediated cardioprotection in vivo. In conclusion, emodin protects the heart from 5/6 nephrectomy-induced mitochondrial damage via activation of the PGC1α signaling. The findings obtained in our study can be used to develop effective therapeutic strategies for patients with CRS4.
Assuntos
Síndrome Cardiorrenal , Emodina , Insuficiência Renal Crônica , Humanos , Camundongos , Animais , Emodina/farmacologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Apoptose , Camundongos Endogâmicos C57BLRESUMO
At least seven cell death programs are activated during myocardial infarction (MI), but which are most important in causing heart damage is not understood. Two of these programs are mitochondrial-dependent necrosis and apoptosis. The canonical function of the pro-cell death BCL-2 family proteins BAX and BAK is to mediate permeabilization of the outer mitochondrial membrane during apoptosis allowing apoptogen release. BAX has also been shown to sensitize cells to mitochondrial-dependent necrosis, although the underlying mechanisms remain ill-defined. Genetic deletion of Bax or both Bax and Bak in mice reduces infarct size following reperfused myocardial infarction (MI/R), but the contribution of BAK itself to cardiomyocyte apoptosis and necrosis and infarction has not been investigated. In this study, we use Bak-deficient mice and isolated adult cardiomyocytes to delineate the role of BAK in the pathogenesis of infarct generation and post-infarct remodeling during MI/R and non-reperfused MI. Generalized homozygous deletion of Bak reduced infarct size â¼50% in MI/R in vivo, which was attributable primarily to decreases in necrosis. Protection from necrosis was also observed in BAK-deficient isolated cardiomyocytes suggesting that the cardioprotection from BAK loss in vivo is at least partially cardiomyocyte-autonomous. Interestingly, heterozygous Bak deletion, in which the heart still retains â¼28% of wild type BAK levels, reduced infarct size to a similar extent as complete BAK absence. In contrast to MI/R, homozygous Bak deletion did not attenuate acute infarct size or long-term scar size, post-infarct remodeling, cardiac dysfunction, or mortality in non-reperfused MI. We conclude that BAK contributes significantly to cardiomyocyte necrosis and infarct generation during MI/R, while its absence does not appear to impact the pathogenesis of non-reperfused MI. These observations suggest BAK may be a therapeutic target for MI/R and that even partial pharmacological antagonism may provide benefit.
Assuntos
Infarto do Miocárdio , Proteína Killer-Antagonista Homóloga a bcl-2 , Animais , Camundongos , Apoptose/fisiologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Homozigoto , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Necrose/genética , Deleção de Sequência , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismoRESUMO
Atmospheric nitrogen (N) deposition is composed of both inorganic nitrogen (IN) and organic nitrogen (ON), and these sources of N may exhibit different impacts on ecosystems. However, our understanding of the impacts of N deposition is largely based on experimental gradients of INs or more rarely ONs. Thus, the effects of N deposition on ecosystem productivity and biodiversity may be biased. We explored the differential impacts of N addition with different IN:ON ratios (0:10, 3:7, 5:5, 7:3, and 10:0) on aboveground net primary productivity (ANPP) of plant community and plant diversity in a typical temperate grassland with a long-term N addition experiment. Soil pH, litter biomass, soil IN concentration, and light penetration were measured to examine the potential mechanisms underlying species loss with N addition. Our results showed that N addition significantly increased plant community ANPP by 68.33%-105.50% and reduced species richness by 16.20%-37.99%. The IN:ON ratios showed no significant effects on plant community ANPP. However, IN-induced species richness loss was about 2.34 times of ON-induced richness loss. Soil pH was positively related to species richness, and they exhibited very similar response patterns to IN:ON ratios. It implies that soil acidification accounts for the different magnitudes of species loss with IN and ON additions. Overall, our study suggests that it might be reasonable to evaluate the effects of N deposition on plant community ANPP with either IN or ON addition. However, the evaluation of N deposition on biodiversity might be overestimated if only IN is added or underestimated if only ON is added.
Assuntos
Ecossistema , Pradaria , Nitrogênio , Biodiversidade , Biomassa , Plantas , SoloRESUMO
SnO2has attracted extensive research attentions as a promising anode material for sodium-ion batteries (SIBs) due to its high theoretical capacity. However, its application is largely hindered by sluggish sodium ion diffusion and drastic volume change during the conversion reaction and alloying process. Herein, ultra-fine SnO2nanocrystals (3-5 nm) anchored on reduced graphene oxide (rGO) is demonstrated as a promising anode material for SIBs. Ultra-fine SnO2nanocrystals are uniformly grown on rGO sheets by a facile one-step hydrothermal process. Nano-scaled SnO2grains tolerate volume expansion and provide shortened diffusion pathway for sodium ions, and meanwhile rGO acts as an excellent conductive matrix, thus endowing the composite electrode with excellent electrochemical performance. More importantly, the ratio of SnO2to rGO in the composite is optimized. The optimized sample delivers an initial charge capacity of 518 mAh g-1at a current density of 50 mA g-1, and 504 mAh g-1after 300 cycles at a current density of 100 mA g-1. Furthermore, a capacity of 287 mAh g-1can be maintained after 1000 cycles at a current density of 1000 mA g-1.
RESUMO
BACKGROUND: Emergence agitation (EA) is a prevalent complication in children following general anesthesia. Several studies have assessed the relationship between melatonin or its analogs and the incidence of pediatric EA, yielding conflicting results. This meta-analysis aims to assess the effects of premedication with melatonin or its analogs on preventing EA in children after general anesthesia. METHODS: PubMed, EMBASE, the Cochrane Library, ProQuest Dissertations & Theses Global, Web of Science, CNKI, Wanfang Data, clinicaltrials.gov, and WHO International Clinical Trials Registry Platform were searched until 25 November 2022. We included randomized controlled trials that assessed EA in patients less than 18 years old who underwent general anesthesia. We excluded studies that did not use a specific evaluation to assess EA. RESULTS: Nine studies (951 participants) were included in this systematic review. Melatonin significantly reduced the incidence of EA compared with placebos (risk ratio 0.40, 95% CI 0.26 to 0.61, P < 0.01) and midazolam (risk ratio 0.48, 95% CI 0.32 to 0.73, P < 0.01). Dexmedetomidine remarkably decreased the incidence of EA compared with melatonin (risk ratio 2.04, 95% CI 1.11 to 3.73, P = 0.02). CONCLUSIONS: Melatonin premedication significantly decreases the incidence of EA compared with placebos and midazolam. Dexmedetomidine premedication has a stronger effect than melatonin in preventing EA. Nevertheless, further studies are warranted to reinforce and validate the conclusion on the efficacy of melatonin premedication in mitigating EA in pediatric patients.
Assuntos
Dexmedetomidina , Delírio do Despertar , Melatonina , Éteres Metílicos , Criança , Humanos , Adolescente , Midazolam , Dexmedetomidina/uso terapêutico , Delírio do Despertar/prevenção & controle , Delírio do Despertar/tratamento farmacológico , Melatonina/uso terapêutico , Sevoflurano , Pré-MedicaçãoRESUMO
Alterations in placental transport may contribute to abnormal fetal intrauterine growth in pregnancies complicated by diabetes, but it is not clear whether the placental amino acid transport system is altered in diabetic pregnancies. We therefore studied the changes in the expressions of placental amino acid transporters in a rat model of diabetes induced by streptozotocin, and tested the effects of hyperglycemia on trophoblast amino acid transporter in vitro. Our results showed that the expressions for key isoforms of system L amino acid transporters were significantly reduced in the placentas of streptozotocin-induced diabetic pregnant rats, which was associated with the decreased birthweight in the rats. A decreased placental efficiency and decreased placental mammalian target of rapamycin (mTOR) complex 1 (mTORC1) activity were also found in the rat model. In addition, hyperglycemia in vitro could inhibit amino acid transporter expression and mTORC1 activity in human trophoblast. Inhibition of mTORC1 activity led to reduced amino acid transporter expression in placental trophoblast. We concluded that reduced placental mTORC1 activity during pregnancy resulted in decreased placental amino acid transporter expression and, subsequently, contributed to fetal intrauterine growth restriction in pregnancies complicated with diabetes.
Assuntos
Sistema A de Transporte de Aminoácidos/metabolismo , Sistema L de Transporte de Aminoácidos/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Retardo do Crescimento Fetal/fisiopatologia , Alvo Mecanístico do Complexo 1 de Rapamicina/biossíntese , Placenta/fisiopatologia , Animais , Linhagem Celular , Feminino , Retardo do Crescimento Fetal/genética , Humanos , Gravidez , Ratos , Ratos Sprague-Dawley , EstreptozocinaRESUMO
Peroxynitrite (OONO(-)) is profoundly implicated in health and disease. The physiological and pathological outcome of OONO(-) is related to its local concentration, and hence, a reliable OONO(-) assay is highly desired. We have developed a FRET-based small-molecule fluorescent probe (PNCy3Cy5), harnessing the differential reactivity of Cy3 and Cy5 toward OONO(-) by fine-tuning. It exhibits high detection sensitivity and yields a ratiometric fluorescent signal. We have exemplified that it can be applied in semiquantitative determination of OONO(-) in living cells. Notably, it specifically localizes in mitochondria, where endogenous OONO(-) is predominantly generated. Thus, PNCy3Cy5 is a promising molecular tool for peroxynitrite biology.
Assuntos
Carbocianinas/química , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Mitocôndrias/metabolismo , Imagem Óptica , Ácido Peroxinitroso/metabolismo , Animais , Camundongos , Ácido Peroxinitroso/química , Células RAW 264.7RESUMO
The excessive elevation of angiotensin II (ANG II) is closely associated with the occurrence and development of aortic dissection (AD)-related acute lung injury (ALI), through its binding to angiotensin II receptor type I (AT1R). MiR-145-5p is a noncoding RNA that can be involved in a variety of cellular physiopathological processes. Transfection with miR-145-5p was found to downregulated the expression of A disintegrin and metalloprotease 17 (ADAM17) and reduced the levels of angiotensin-converting enzyme 2 (ACE2) in lung tissue, while concurrently increasing plasma ACE2 levels in the AD combined with ALI mice. ADAM17 was proved to be a target of miR-145-5p. Transfection with miR-145-5p decreased the shedding of ACE2 and alleviated the inflammatory response induced by ANG II through targeting ADAM17 and inhibiting the AT1R/ADAM17 pathway in A549 cells. In conclusion, our present study demonstrates the role and mechanism of miR-145-5p in alleviating ANG II-induced acute lung injury, providing a new insight into miRNA therapy for reducing lung injury in patients with aortic dissection.
Assuntos
Lesão Pulmonar Aguda , Dissecção Aórtica , MicroRNAs , Humanos , Animais , Camundongos , Enzima de Conversão de Angiotensina 2/genética , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Células Epiteliais Alveolares/metabolismo , Proteína ADAM17/genética , Angiotensina II/farmacologia , Angiotensina II/metabolismo , MicroRNAs/genética , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismoRESUMO
Endoplasmic reticulum (ER) stress and chronic sterile inflammation are associated with the pathogenesis of diabetic nephropathy (DN). Catechins are natural polyphenolic compounds found in green tea that possess some health benefits. However, whether (+)-catechin can reduce tubular injury in DN by regulating ER stress and NLRP3-associated inflammation remains uncertain. This study examined the effects of (+)-catechin on streptozotocin (STZ)-induced diabetic mice and on palmitic acid (PA)-treated HK-2 cells. In vivo, a DN mouse model was generated by injecting STZ. The biochemical indicators of serum and urine, as well as renal histopathology and ultrastructure were analysed. To predict the mechanisms associated with (+)-catechin, network pharmacology and molecular docking were used. Finally, quantitative real-time PCR (qPCR), western blot analysis and immunofluorescence analysis were performed to measure the mRNA and protein expressions of specific targets in the renal tissue of DN mice and PA-treated HK-2 cells to validate the predicted results. (+)-Catechin significantly ameliorated renal function and pathological changes associated with tubular injury by inhibiting ER stress by downregulating of GRP78, PEAK, CHOP, ATF6 and XBP1. In addition, (+)-catechin inhibited renal inflammation by suppressing NLRP3 associated inflammation, which was characterized by the downregulation of NLRP3, ASC, AIM2, Caspase1, IL-1ß and IL-18 in DN mice and PA-treated HK-2 cells. Collectively, these findings suggested that (+)-catechin exerted a renoprotective effect against DN by inhibiting ER stress and NLRP3-related inflammation to ameliorate tubular injury, suggesting the therapeutic potential of (+)-catechin.
Assuntos
Catequina , Nefropatias Diabéticas , Estresse do Retículo Endoplasmático , Inflamação , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Humanos , Masculino , Camundongos , Catequina/farmacologia , Linhagem Celular , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Inflamação/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/metabolismo , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismoRESUMO
Background: In recent years, diabetic kidney disease (DKD) has emerged as a prominent factor contributing to end-stage renal disease. Tubulointerstitial inflammation and lipid accumulation have been identified as key factors in the development of DKD. Earlier research indicated that Astragaloside IV (AS-IV) reduces inflammation and oxidative stress, controls lipid accumulation, and provides protection to the kidneys. Nevertheless, the mechanisms responsible for its protective effects against DKD have not yet been completely elucidated. Purpose: The primary objective of this research was to examine the protective properties of AS-IV against DKD and investigate the underlying mechanism, which involves CD36, reactive oxygen species (ROS), NLR family pyrin domain containing 3 (NLRP3), and interleukin-1ß (IL-1ß). Methods: The DKD rat model was created by administering streptozotocin along with a high-fat diet. Subsequently, the DKD rats and palmitic acid (PA)-induced HK-2 cells were treated with AS-IV. Atorvastatin was used as the positive control. To assess the therapeutic effects of AS-IV on DKD, various tests including blood sugar levels, the lipid profile, renal function, and histopathological examinations were conducted. The levels of CD36, ROS, NLRP3, Caspase-1, and IL-1ß were detected using western blot analysis, PCR, and flow cytometry. Furthermore, adenovirus-mediated CD36 overexpression was applied to explore the underlying mechanisms through in vitro experiments. Results: In vivo experiments demonstrated that AS-IV significantly reduced hyperglycemia, dyslipidemia, urinary albumin excretion, and serum creatinine levels in DKD rats. Additionally, it improved renal structural abnormalities and suppressed the expression of CD36, NLRP3, IL-1ß, TNF-α, and MCP-1. In vitro experiments showed that AS-IV decreased CD36 expression, lipid accumulation, and lipid ROS production while inhibiting NLRP3 activation and IL-1ß secretion in PA-induced HK-2 cells. Conclusion: AS-IV alleviated renal tubule interstitial inflammation and tubule epithelial cell apoptosis in DKD rats by inhibiting CD36-mediated lipid accumulation and NLRP3 inflammasome activation.
RESUMO
BACKGROUND: Tinosporae radix is the root tuber of Tinospora capillipes Gagnep of the Menispermaceae family. It has the effects of clearing away heat and toxins, benefiting the throat, relieving pain, and treating sore throat, carbuncle and boils, and other diseases in clinical practice. METHODS: The related references about T. radix in this review were collected by online databases, including PubMed, Elsevier, Web of Science, Willy, SciFinder, SpringLink, Google Scholar, Baidu Scholar, ACS publications, Scopus, and CNKI. The other information about T. radix was acquired from ancient books and classical works. RESULTS: T. radix is an important medicinal plant with a variety of traditional uses according to the theory of Chinese medicine. Previous studies revealed that T. radix contained a variety of chemical components, including diterpenoids, alkaloids, steroids, cinnamic acid derivatives, and other compounds. Many pharmacological researches have exhibited that T. radix possesses various biological activities, including anti-cancer, hypoglycemic, anti-inflammatory, anti-bacterial, anti-ulcer, and anti-oxidant activities. Furthermore, the quality markers of T. radix were summarized and analyzed in this paper. CONCLUSION: The traditional use, botany, phytochemistry, bioactivity, and quality markers of T. radix were reviewed in this paper. It will not only provide an important clue for further studying T. radix, but also supply an important theoretical basis and a valuable reference for in-depth research and exploitations of this plant in the future.
RESUMO
Ferroptosis, a regulated form of cell death, is characterized by iron-dependent lipid peroxidation leading to oxidative damage to cell membranes. Cell sensitivity to ferroptosis is influenced by factors such as iron overload, lipid metabolism, and the regulation of the antioxidant system. Melatonin, with its demonstrated capacity to chelate iron, modulate iron metabolism proteins, regulate lipid peroxidation, and regulate antioxidant systems, has promise as a potential therapeutic agent in mediating ferroptosis. The availability of approved drugs targeting ferroptosis is limited; therefore, melatonin is a candidate for broad application due to its safety and efficacy in attenuating ferroptosis in noncancerous diseases. Melatonin has been demonstrated to attenuate ferroptosis in cellular and animal models of noncancerous diseases, showcasing effectiveness in organs such as the heart, brain, lung, liver, kidney, and bone. This review outlines the molecular mechanisms of ferroptosis, investigates melatonin's potential effects on ferroptosis, and discusses melatonin's therapeutic potential as a promising intervention against diseases associated with ferroptosis. Through this discourse, we aim to lay a strong foundation for developing melatonin as a therapeutic strategy to modulate ferroptosis in a variety of disease contexts.
Assuntos
Ferroptose , Melatonina , Animais , Melatonina/farmacologia , Melatonina/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Ferro/metabolismo , Morte Celular , Peroxidação de LipídeosRESUMO
Computing in memory (CIM) based on memristors is expected to completely solve the dilemma caused by von Neumann architecture. However, the performance of memristors based on traditional conductive filament mechanism is unstable. In this study, we report a nonvolatile high-performance memristor based on ferroelectric tunnel junction (FTJ) Pd/Bi0.9La0.1FeO3 (6.9 nm) (BLFO)/La0.67Sr0.33MnO3 (LSMO) on a silicon substrate. The conductance of this device was adjusted by different pulse stimulation parameter to achieve various synaptic functions because of ferroelectric polarization reversal. Based on the multiple conductance characteristics of the devices and the high linearity and symmetry of weight updating, image processing and VGG8 convolutional neural network (CNN) simulation based on the devices were realized. Excellent results of the image processing are demonstrated. The recognition accuracy of CNN offline learning reached an astonishing 92.07% based on Cifar-10 dataset. This provides a more feasible solution to break through the bottleneck of von Neumann architecture.
RESUMO
Neuromorphic computing based on memristors capable of in-memory computing is promising to break the energy and efficiency bottleneck of well-known von Neumann architectures. However, unstable and nonlinear conductance updates compromise the recognition accuracy and block the integration of neural network hardware. To this end, we present a highly stable memristor with self-assembled vertically aligned nanocomposite (VAN) SrTiO3:MgO films that achieve excellent resistive switching with low set/reset voltage variability (4.7%/-5.6%) and highly linear conductivity variation (nonlinearity = 0.34) by spatially limiting the conductive channels at the vertical interfaces. Various synaptic behaviors are simulated by continuously modulating the conductance. Especially, convolutional image processing using diverse crossbar kernels is demonstrated, and the artificial neural network achieves an overwhelming recognition accuracy of up to 97.50% for handwritten digits. Even under the perturbation of Poisson noise (λ = 10), 6% Salt and Pepper noise, and 5% Gaussian noise, the high recognition accuracies are retained at 95.43%, 94.56%, and 95.97%, respectively. Importantly, the logic memory function is proven experimentally based on the nonvolatile properties. This work provides a material system and design idea to achieve high-performance neuromorphic computing and logic operation.
RESUMO
Pore-forming toxins (PFTs) are important virulence factors produced by many pathogenic bacteria. Here, we show that the Vibrio cholerae toxin MakA is a novel cholesterol-binding PFT that induces non-canonical autophagy in a pH-dependent manner. MakA specifically binds to cholesterol on the membrane at pH < 7. Cholesterol-binding leads to oligomerization of MakA on the membrane and pore formation at pH 5.5. Unlike other cholesterol-dependent cytolysins (CDCs) which bind cholesterol through a conserved cholesterol-binding motif (Thr-Leu pair), MakA contains an Ile-Ile pair that is essential for MakA-cholesterol interaction. Following internalization, endosomal acidification triggers MakA pore-assembly followed by ESCRT-mediated membrane repair and V-ATPase-dependent unconventional LC3 lipidation on the damaged endolysosomal membranes. These findings characterize a new cholesterol-binding toxin that forms pores in a pH-dependent manner and reveals the molecular mechanism of host autophagy manipulation.
Assuntos
Autofagia , Proteínas de Bactérias , Colesterol , Citotoxinas , Vibrio cholerae , Fatores de Virulência , Adenosina Trifosfatases/metabolismo , Motivos de Aminoácidos , Autofagia/efeitos dos fármacos , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Colesterol/metabolismo , Citotoxinas/metabolismo , Citotoxinas/farmacologia , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Endossomos/química , Endossomos/metabolismo , Concentração de Íons de Hidrogênio , Lisossomos/química , Lisossomos/metabolismo , Ligação Proteica , Vibrio cholerae/química , Vibrio cholerae/metabolismo , Fatores de Virulência/química , Fatores de Virulência/metabolismoRESUMO
Vitamin D insufficiency/deficiency has been linked to an increased risk of preeclampsia. Impaired placental amino acid transport is suggested to contribute to abnormal fetal intrauterine growth in pregnancies complicated by preeclampsia. However, if vitamin D-regulated amino acid transporter is involved in the pathophysiologic mechanism of preeclampsia has not been clarified yet. The aberrant expression of key isoform of L-type amino acid transporter LAT1 was determined by western blot and immunohistochemistry in the placenta from normotensive and preeclamptic pregnancies. The role for vitamin D on placental LAT1 expression was investigated through the exposure of HTR-8/SVneo human trophoblast cells to the biologically active 1,25(OH)2D3 and the oxidative stress-inducer cobalt chloride (CoCl2). Our results showed that placental LAT1 expression was reduced in women with preeclampsia compared to normotensive pregnancies, which was associated with decreased expression of vitamin D receptor (VDR). 1,25(OH)2D3 significantly upregulated LAT1 expression in placental trophoblasts, and also prevented the decrease of mTOR activity under CoCl2-induced oxidative stress. siRNA targeting VDR significantly attenuated 1,25(OH)2D3-stimulated LAT1 expression and mTOR signaling activity. Moreover, treatment of rapamycin specifically inhibited the activity of mTOR signaling and resulted in decrease of LAT1 expression. In conclusion, LAT1 expression was downregulated in the placenta from women with preeclampsia. 1,25(OH)2D3/VDR could stimulate LAT1 expression, which was likely mediated by mTOR signaling in placental trophoblasts. Regulation on placental amino acid transport may be one of the mechanisms by which vitamin D affects fetal growth in preeclampsia.
Assuntos
Placenta , Pré-Eclâmpsia , Sistemas de Transporte de Aminoácidos/metabolismo , Aminoácidos/metabolismo , Feminino , Humanos , Transportador 1 de Aminoácidos Neutros Grandes , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Serina-Treonina Quinases TOR/metabolismo , Trofoblastos/metabolismo , Vitamina D/metabolismo , Vitamina D/farmacologia , Vitaminas/metabolismoRESUMO
Increased nitrogen (N) deposition is known to reduce the ecosystem stability, while the underlying mechanisms are still controversial. We conducted an 8-year multi-level N addition experiment in a temperate semi-arid grassland to identify the mechanisms (biodiversity, species asynchrony, population stability and dominant species stability) driving the N-induced loss of temporal stability of aboveground net primary productivity (ANPP). We found that N addition decreased ecosystem, population, and dominant species stability; decreased species richness and phylogenetic diversity; increased species dominance; but had nonsignificant effects on community-wide species asynchrony. Structural equation model revealed that N-induced loss of ecosystem stability was mainly driven by the loss of dominant species stability and the reduction in population stability. Moreover, species relative instability was negatively related with species relative production and the slopes increase with N addition, indicating that N addition weakened the stabilizing effect of dominant species on ecosystem function. Overall, our results highlight that the dominant species control the temporal stability of ANPP in grassland ecosystem under N addition, and support 'dominance management' as an effective strategy for conserving ecosystem functioning in grassland under N deposition.
Assuntos
Ecossistema , Nitrogênio , Biodiversidade , Pradaria , FilogeniaRESUMO
Fluorine emission from domestic wastewater is a major cause of severe environmental issues. In this paper, the density functional theory has been used to reveal the adsorption properties of F- ions and HF molecules on intrinsic graphene, B-doped graphene, and Al-doped graphene. Throughout the analysis of band structure, geometric structure, adsorption energy, charge transfer, charge density, density of states, and frontier orbital, we can find that the adsorption of F- ions and HF molecules on intrinsic graphene and HF molecules on B-doped graphene is weak, and it is only physical adsorption. When F- ions and HF molecules are adsorbed on Al-doped graphene and F- ions adsorbed on B-doped graphene, the adsorption energy, charge transfer, and charge density greatly increase, and the adsorption distance significantly decreases, and there exist obvious hybridizations by analyzing the charge density and density of states. We can also find that Al-doped graphene is more sensitive to F- ions after comparing the variation of band gap. The work conducted in this research provides a theoretical guidance for the application of fluorine sensors based on graphene.