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1.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167299, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878833

RESUMO

STING (stimulator of interferon genes) is a critical immunoregulatory protein in sepsis and is regulated by various mechanisms, especially palmitoylation. FASN (fatty acid synthase) is the rate-limiting enzyme to generate cellular palmitic acid (PA) via acetyl-CoA and malonyl-CoA and participates in protein palmitoylation. However, the mechanisms underlying the interaction between STING and FASN have not been completely understood. In this study, STING-knockout mice were used to confirm the pivotal role of STING in sepsis-induced liver injury. Metabolomics confirmed the dyslipidemia in septic mice and patients. The compounds library was screened, revealing that FASN inhibitors exerted a significant inhibitory effect on the STING pathway. Mechanically, the regulatory effect of FASN on the STING pathway was dependent on palmitoylation. Further experiments indicated that the upstream of FASN, malonyl-CoA inhibited STING pathway possibly due to C91 (palmitoylated residue) of STING. Overall, this study reveals a novel paradigm of STING regulation and provides a new perspective on immunity and metabolism.

2.
Ecotoxicol Environ Saf ; 281: 116570, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38896902

RESUMO

Rice is one of the most important staple food crops; however, it is prone to cadmium (Cd) accumulation, which has negative health effects. Therefore, methods to reduce Cd uptake by rice are necessary. At present, there is limited research on the effects of co-application of silicon (Si) and goethite in mitigating Cd stress in rice. Furthermore, the specific mechanisms underlying the effects of their combined application on iron plaque formation in rice roots remain unclear. Therefore, this study analyzed the effects of the combined application of Si and goethite on the biomass, physiological stress indicators, Cd concentration, and iron plaques of rice using hydroponic experiments. The results revealed that co-treatment with both Si and goethite increased the plant height and dry weight, superoxide dismutase and catalase activities, photosynthetic pigment concentration, and root activity. Moreover, this treatment decreased the malondialdehyde concentration, repaired epidermal cells, reduced the Cd concentration in the roots by 57.2 %, and increased the number of iron plaques and Cd concentration by 150.9 % and 266.2 % in the amorphous and crystalline fractions, respectively. The Cd/Fe ratio in amorphous iron plaques also increased. Our findings suggest that goethite serves as a raw material for iron plaque formation, while Si enhances the oxidation capacity of rice roots. The application of a combination of Si and goethite increases the quantity and quality of iron plaques, enhancing its Cd fixation capacity. This study provides theoretical evidence for the effective inhibition of Cd uptake by iron plaques in rice, providing insights into methods for the remediation of Cd contamination.

3.
Hypertens Res ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778170

RESUMO

To explore the mechanism of the hypertension in dopamine receptor-4 (Drd4) null mice, we determined the salt sensitivity and renal sodium transport proteins in Drd4-/- and Drd4+/+ mice with varied salt diets. On normal NaCl diet (NS), mean arterial pressures (MAP, telemetry) were higher in Drd4-/- than Drd4+/+; Low NaCl diet (LS) tended to decrease MAP in both strains; high NaCl diet (HS) elevated MAP with sodium excretion decreased and pressure-natriuresis curve shifted to right in Drd4-/- relative to Drd4+/+ mice. Drd4-/- mice exhibited increased renal sodium-hydrogen exchanger 3 (NHE3), sodium-potassium-2-chloride cotransporter (NKCC2), sodium-chloride cotransporter (NCC), and outer medullary α-epithelial sodium channel (αENaC) on NS, decreased NKCC2, NCC, αENaC, and αNa+-K+-ATPase on LS, and increased αENaC on HS. NKCC2, NCC, αENaC, and αNa+-K+-ATPase in plasma membrane were greater in Drd4-/- than in Drd4+/+ mice with HS. D4R was expressed in proximal and distal convoluted tubules, thick ascending limbs, and outer medullary collecting ducts and colocalized with NKCC2 and NCC. The phosphorylation of NKCC2 was enhanced but ubiquitination was reduced in the KO mice. There were no differences between the mouse strains in serum aldosterone concentrations and urinary dopamine excretions despite their changes with diets. The mRNA expressions of renal NHE3, NKCC2, NCC, and αENaC on NS were not altered in Drd4-/- mice. Thus, increased protein expressions of NHE3, NKCC2, NCC and αENaC are associated with hypertension in Drd4-/- mice; increased plasma membrane protein expression of NKCC2, NCC, αENaC, and αNa+-K+-ATPase may mediate the salt sensitivity of Drd4-/- mice.

4.
Mol Neurobiol ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427211

RESUMO

The exact relationship between nicotine metabolism and dependence is not fully understood but is known to be influenced at a molecular level by genetic factors. A sample comprising 274 Chinese adult male smokers was categorized into groups based on their metabolic rates, namely fast, intermediate, and slow metabolizers. We then measured their smoking topography, evaluated their nicotine dependence, and assessed the rewarding effects. Based on these findings, we proposed the hypothesis that the rate of nicotine metabolism could influence the level of dopamine release which in turn had repercussions on the pleasurable and rewarding effects. To test this hypothesis, male mice were selected with different nicotine metabolic rates that closely resembled in the smoker group. We evaluated their nicotine dependence and rewarding effects through conditioned place preference and withdrawal symptom tests, supplemented with dopamine release measurements. In both animal and human, the slow metabolism group (SMG) required less nicotine to maintain a comparable level of dependence than the fast metabolism group (FMG). The SMG could achieve similar rewarding effects to FMG despite consuming less nicotine. Comparable dopamine levels released were therefore critical in setting the nicotine acquisition behavior in this animal model and also for the smokers tested. Our findings suggested that even within the same ethnicity of established smokers (Chinese Han), differences in nicotine metabolism were an important parameter to modulate the degree of nicotine dependence.

5.
FASEB J ; 38(6): e23537, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38498345

RESUMO

Candesartan is a common angiotensin-II receptor-1 blocker used for patients with cardiovascular and renal diseases. Angiotensin-converting enzyme 2 (ACE2) is a negative regulator of blood pressure (BP), and also a major receptor for coronaviruses. To determine whether and how candesartan upregulates ACE2, we examined BP and ACE2 in multi-organs from male and female C57BL/6J mice treated with candesartan (1 mg/kg, i.p.) for 7 days. Relative to the vehicle, candesartan lowered BP more in males than females; ACE2 protein abundances were increased in kidneys, not lungs, hearts, aorta, liver, spleen, brain, or serum, only from males. Ace2-mRNA was similar in kidneys. Candesartan also decreased BP in normal, hypertensive, and nephrotic male rats. The renal ACE2 was increased by the drug in normal and nephrotic male rats but not spontaneously hypertensive ones. In male mouse kidneys, ACE2 was distributed at sodium-hydrogen-exchanger-3 positive proximal-convoluted-tubules; ACE2-ubiquitination was decreased by candesartan, accompanied with increased ubiquitin-specific-protease-48 (USP48). In candesartan-treated mouse renal proximal-convoluted-tubule cells, ACE2 abundances and activities were increased while ACE2-ubiquitination and colocalization with lysosomal and proteosomal markers were decreased. The silence of USP48 by siRNA caused a reduction of ACE2 in the cells. Thus, the sex-differential ACE2 upregulation by candesartan in kidney from males may be due to the decreased ACE2-ubiquitination, associated with USP48, and consequent degradation in lysosomes and proteosomes. This is a novel mechanism and may shed light on candesartan-like-drug choice in men and women prone to coronavirus infections.


Assuntos
Enzima de Conversão de Angiotensina 2 , Benzimidazóis , Compostos de Bifenilo , Hipertensão , Humanos , Feminino , Masculino , Ratos , Camundongos , Animais , Enzima de Conversão de Angiotensina 2/metabolismo , Camundongos Endogâmicos C57BL , Rim/metabolismo , Hipertensão/metabolismo , Tetrazóis/farmacologia , Ubiquitinação
6.
World J Clin Cases ; 12(7): 1320-1325, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38524521

RESUMO

BACKGROUND: Developmental dysplasia of the hip (DDH) is a common osteoarticular deformity in pediatric orthopedics. A patient with bilateral DDH was diagnosed and treated using our improved technique "(powerful overturning acetabuloplasty)" combined with femoral rotational shortening osteotomy. CASE SUMMARY: A 4-year-old girl who was diagnosed with bilateral DDH could not stand normally, and sought surgical treatment to solve the problem of double hip extension and standing. As this child had high dislocation of the hip joint and the acetabular index was high, we changed the traditional acetabuloplasty to "powerful turnover acetabuloplasty" combined with femoral rotation shortening osteotomy. During the short-term postoperative follow-up (1, 3, 6, 9, 12, and 15 months), the child had no discomfort in her lower limbs. After the braces and internal fixation plates were removed, formal rehabilitation training was actively carried out. CONCLUSION: Our "powerful overturning acetabuloplasty" combined with femoral rotational shortening osteotomy is feasible in the treatment of DDH in children. This technology may be widely used in the clinic.

7.
J Acoust Soc Am ; 155(2): 1119-1134, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38341740

RESUMO

A feature matching method based on the convolutional neural network (named FM-CNN), inspired from matched-field processing (MFP), is proposed to estimate source depth in shallow water. The FM-CNN, trained on the acoustic field replicas of a single source generated by an acoustic propagation model in a range-independent environment, is used to estimate single and multiple source depths in range-independent and mildly range-dependent environments. The performance of the FM-CNN is compared to the conventional MFP method. Sensitivity analysis for the two methods is performed to study the impact of different environmental mismatches (i.e., bottom parameters, water column sound speed profile, and topography) on depth estimation performance in the East China Sea environment. Simulation results demonstrate that the FM-CNN is more robust to the environmental mismatch in both single and multiple source depth estimation than the conventional MFP. The proposed FM-CNN is validated by real data collected from four tracks in the East China Sea experiment. Experimental results demonstrate that the FM-CNN is capable of reliably estimating single and multiple source depths in complex environments, while MFP has a large failure probability due to the presence of strong sidelobes and wide mainlobes.

8.
bioRxiv ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38405772

RESUMO

BACKGROUND: The thiazide-sensitive sodium chloride cotransporter (NCC) is the major apical sodium transporter located in the mammalian renal distal convoluted tubule (DCT). The amount of sodium reabsorbed in the DCT through NCC plays an important role in the regulation of extracellular fluid volume and blood pressure. Dopamine and its receptors constitute a renal antihypertensive system in mammals. The disruption of Drd4 in mice causes kidney-related hypertension. However, the pathogenesis of D4R-deficiency associated hypertension is not well documented. METHOD: We assessed the effects of D4R on NCC protein abundances and activities of DCT in mice with renal or global Drd4-deficiencies and expressing human D4.7 variant and in cultured mouse DCT cells, and explored the molecular mechanism. RESULTS: NCC inhibitor hydrochlorothiazide enhanced the natriuresis in Drd4-/- mice. Renal NCC protein was greater while ubiquitination of NCC was less in Drd4-/- than Drd4+/+ mice. Silencing of D4R in cultured mouse DCT cells increased NCC protein but decreased NCC ubiquitination. D4R agonist had opposite effects that were blocked by the antagonist. In mouse kidneys and DCT cells D4R and NCC colocalized and co-immunoprecipitated. Moreover, D4R-agonist promoted the binding between the two proteins demonstrated by fluorescence resonance energy transfer. D4R agonism internalized NCC, decreased NCC in the plasma membrane, increased NCC in lysosomes and reduced NCC-dependent-intracellular-sodium transport. The lysosomal inhibitor chloroquine prevented the D4R-induced NCC-reduction. A shortened NCC half-life was suggested by its decay under cycloheximide-chase. Ubiquitin-specific-protease 48 (USP48, a deubiquitinating enzyme) was increased in the kidneys and cells with Drd4-deficiency while D4R stimulation decreased it in vitro and reduction of USP48 with siRNA decreased NCC expression. The mice carrying human D4.7 variant or with renal supcapsular-Drd4-siRNA-delivery developed hypertension with increased NCC. CONCLUSION: Our data demonstrates that D4R downregulates NCC by promoting USP48-associated deubiquitination and subsequent internalization, lysosome relocation and degradation.

9.
Cell Mol Life Sci ; 80(11): 337, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37897551

RESUMO

Hypervirulent Klebsiella pneumoniae (hvKP) is a highly lethal opportunistic pathogen that elicits more severe inflammatory responses compared to classical Klebsiella pneumoniae (cKP). In this study, we investigated the interaction between hvKP infection and the anti-inflammatory immune response gene 1 (IRG1)-itaconate axis. Firstly, we demonstrated the activation of the IRG1-itaconate axis induced by hvKP, with a dependency on SYK signaling rather than STING. Importantly, we discovered that exogenous supplementation of itaconate effectively inhibited excessive inflammation by directly inhibiting SYK kinase at the 593 site through alkylation. Furthermore, our study revealed that itaconate effectively suppressed the classical activation phenotype (M1 phenotype) and macrophage cell death induced by hvKP. In vivo experiments demonstrated that itaconate administration mitigated hvKP-induced disturbances in intestinal immunopathology and homeostasis, including the restoration of intestinal barrier integrity and alleviation of dysbiosis in the gut microbiota, ultimately preventing fatal injury. Overall, our study expands the current understanding of the IRG1-itaconate axis in hvKP infection, providing a promising foundation for the development of innovative therapeutic strategies utilizing itaconate for the treatment of hvKP infections.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Humanos , Klebsiella pneumoniae/genética , Disbiose/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Inflamação/tratamento farmacológico , Alquilação , Quinase Syk
10.
Environ Int ; 179: 108162, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37688807

RESUMO

The potential toxicity of Cd to soil and rice plant severely threaten human health. This study was conducted to investigate the remediation effects of blast furnace slag (BFS) on the bioavailability of Cd in a contaminated paddy soil from a perspective of soil solution chemistry. Batch experiments, pot culture experiments, and principal analysis (PCA) were used to study the effects and mechanisms of BFS addition changing Cd chemical behavior and Cd toxicity. Results indicated that BFS facilitated Cd adsorption in soils, increased pH, Eh, and EC values in soil solution, whereas reduced dissolved Cd content. BFS amendment was efficient in decreasing root Cd intake and Cd upward transport in rice plant, with the Cd translocation factor in brown rice decreased by âˆ¼ 75% (BFS treatment, 6‰ wt) relative to Cd treatment, which in turn increased rice biomass and grain yield. PCA indicated that the dissolved Cd concentration had a close relationship with soil pH and metal concentration in soil solution. Results from this study indicated that BFS had potential ability for either immobilization or remobilization of Cd in soils, and the findings have important implications for Cd-polluted soil remediation or other resource utilization with slag-based materials.


Assuntos
Cádmio , Oryza , Humanos , Cádmio/toxicidade , Transporte Biológico , Adsorção , Disponibilidade Biológica , Solo , Translocação Genética
11.
Ying Yong Sheng Tai Xue Bao ; 34(7): 1883-1891, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37694472

RESUMO

Scientific evaluating ecosystem service value (ESV) of cover crop cultivation system can provide important guidance for the construction of conservation tillage pattern in Northeast China. Based on empirical analysis and the theory of ecosystem service value, we calculated the ESVs of intercropping maize with gramineous cover crop ryegrass and with leguminous cover crops, alfalfa and hairy vetch, with maize monoculture as the control. The ESVs included product supply, gas regulation, nutrient cycling, and soil and water conservation. Results showed that ESVs of cover crop-maize intercropping were higher than those of maize monoculture. Nutrient cycling value was the highest, followed by product supply value, accounting for 67.3% and 29.3% of total ESV, respectively. The nutrient cycling value of cover crop-maize intercropping was higher than that of maize monoculture. The product supply value of alfalfa-maize and hairy vetch-maize were 18.7% and 21.0% higher than that of ryegrass-maize, respectively. Cover crops had the potential to increase the value of gas regulation services, but had little impact on the value of soil and water conservation. Considering the ESVs, intercropping maize with leguminous cover crops would have the greatest benefits.


Assuntos
Lolium , Vicia , Zea mays , Ecossistema , China , Produtos Agrícolas , Medicago sativa , Solo , Verduras
12.
Biomed Pharmacother ; 162: 114694, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37054540

RESUMO

Diabetic nephropathy (DN) is a common microvascular complication of both type 1 and type 2 diabetes mellitus and often advances to end-stage renal disease. Oxidative stress plays an important role in the pathogenesis and progress of DN. Hydrogen sulfide (H2S) is considered as a promising candidate for the management of DN. But the antioxidant effects of H2S in DN have not been fully studied. In mouse model induced by high-fat diet and streptozotocin, GYY4137, a H2S donor, ameliorated albuminuria at weeks 6 & 8 and decreased serum creatinine at week 8, but not hyperglycemia. Renal nitrotyrosine and urinary 8-isoprostane were reduced along with the suppressed levels of renal laminin and kidney-injury-molecule 1. Renal NADPH oxidase (NOX) 2 was lower but heme oxygenase (HO) 2, paraoxonase (PON) 1, PON2 were higher in DN+GYY than DN group. NOX1, NOX4, HO1, superoxide dismutases 1-3 were similar between groups. Except for a rise at HO2, all the affected enzymes were unchanged in mRNA levels. The affected reactive-oxygen-species (ROS) enzymes were mainly located in the renal sodium-hydrogen-exchanger positive proximal tubules with similar distribution but changed immunofluorence in GYY4137 treated DN mice. Kidney morphological alterations in DN mice under light and electrical-microscopes were also improved by GYY4137. Thus, exogenous H2S administration may improve the renal oxidative damage in DN by reducing ROS production and enhancing ROS cleavage in kidney via the affected enzymes. This study may shed a light on therapeutic applications in diabetic nephropathy with H2S donors in the future.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Camundongos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Rim/patologia , Estresse Oxidativo
13.
JASA Express Lett ; 3(2): 026003, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36858986

RESUMO

Neural networks have been applied to underwater source localization and achieved better performance than the conventional matched-field processing (MFP). However, compared with MFP, the neural networks lack physical interpretability. In this work, an interpretable complex convolutional neural network based on Bartlett processor (BC-CNN) for underwater source localization is designed, the output and structure of which have clear physical meanings. The relationship between the convolution weights of BC-CNN and replica pressure of MFP is discussed, which effectively presents the interpretability of the BC-CNN. Simulation experiments using two kinds of labels demonstrate the equivalence between the Bartlett MFP and BC-CNN.

14.
Cell Rep ; 42(3): 112145, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36862550

RESUMO

The Krebs cycle-derived metabolite itaconate, whose production is catalyzed by immune response gene 1 (IRG1), has potential to link immunity and metabolism in activated macrophages through alkylation or competitive inhibition of target proteins. In support of this, our previous study demonstrated that the stimulator of interferon genes (STING) signaling platform functions as a hub in macrophage immunity and has a profound impact on the prognosis of sepsis. Interestingly, we find that itaconate, an endogenous immunomodulator, can significantly inhibit the activation of STING signaling. Moreover, 4-octyl itaconate (4-OI), which is a permeable itaconate derivative, can alkylate cysteine sites 65, 71, 88, and 147 of STING, thereby inhibiting its phosphorylation. Furthermore, itaconate and 4-OI inhibit the production of inflammatory factors in sepsis models. Our results broaden the knowledge on the role of the IRG1-itaconate axis in immunomodulation and highlight itaconate and its derivatives as potential therapeutic agents in sepsis.


Assuntos
Inflamação , Succinatos , Humanos , Alquilação , Inflamação/tratamento farmacológico , Proteínas/metabolismo , Succinatos/farmacologia , Succinatos/metabolismo , Proteínas de Membrana
15.
FASEB J ; 37(4): e22834, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36961378

RESUMO

The kidney regulates blood pressure through salt/water reabsorption affected by tubular sodium transporters. Expanding our prior research on placental cluster of differentiation 81 (CD81), this study explores the interaction of renal CD81 with sodium transporters in preeclampsia (PE). Effects of renal CD81 with sodium transporters were determined in lipopolysaccharide (LPS)-induced PE rats and immortalized mouse renal distal convoluted tubule cells. Urinary exosomal CD81, sodium potassium 2 chloride cotransporter (NKCC2), and sodium chloride cotransporter (NCC) were measured in PE patients. LPS-PE rats had hypertension from gestational days (GD) 6 to 18 and proteinuria from GD9 to GD18. Urinary CD81 in both groups tented to rise during pregnancy. Renal CD81, not sodium transporters, was higher in LPS-PE than controls on GD14. On GD18, LPS-PE rats exhibited higher CD81 in kidneys and urine exosomes, higher renal total and phosphorylated renal NKCC2 and NCC with elevated mRNAs, and lower ubiquitinated NCC than controls. CD81 was co-immunoprecipitated with NKCC2 or NCC in kidney homogenates and co-immunostained with NKCC2 or NCC in apical membranes of renal tubules. In plasma membrane fractions, LPS-PE rats had greater amounts of CD81, NKCC2, and NCC than controls with enhanced co-immunoprecipitations of CD81 with NKCC2 or NCC. In renal distal convoluted tubule cells, silencing CD81 with siRNA inhibited NCC and prevented LPS-induced NCC elevation. Further, PE patients had higher CD81 in original urines, urine exosomes and higher NKCC2 and NCC in urine exosomes than controls. Thus, the upregulation of renal CD81 on NKCC2 and NCC may contribute to the sustained hypertension observed in LPS-PE model. Urine CD81 with NKCC2 and NCC may be used as biomarkers for PE.


Assuntos
Hipertensão , Pré-Eclâmpsia , Gravidez , Camundongos , Humanos , Ratos , Feminino , Animais , Simportadores de Cloreto de Sódio-Potássio/metabolismo , Simportadores de Cloreto de Sódio/genética , Simportadores de Cloreto de Sódio/metabolismo , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Cloretos/metabolismo , Pré-Eclâmpsia/induzido quimicamente , Pré-Eclâmpsia/metabolismo , Membro 1 da Família 12 de Carreador de Soluto/metabolismo , Placenta/metabolismo , Túbulos Renais Distais/metabolismo , Hipertensão/metabolismo , Sódio/metabolismo , Potássio/metabolismo , Tetraspanina 28/metabolismo
16.
Biomed Pharmacother ; 161: 114484, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36921530

RESUMO

A low-salt diet may activate the renin-angiotensin-aldosterone system (RAAS) and is often applied simultaneously with RAAS inhibitors, especially for treatment of proteinuric nephritis. To explore the effect of a low-salt diet combined with angiotensin receptor blockers (ARB) on kidney function, the proteinuric nephritis model was induced by single intravenous injection of doxorubicin, and then the SD rats were administrated with candesartan intraperitoneal injection and fed with different salt diets. Rats with low-salt plus candesartan, not either alone, experienced acute kidney injury (AKI) at day 7 and could not self-restore when extending the experiment time from 7 days to 21 days, unless switching low-salt to normal-salt. Among three nitric oxide synthetases (NOS), endothelial NOS (eNOS) was obviously elevated and PI3K-Akt-eNOS signal pathway was activated. NG-Nitro-L-Arginine Methyl Ester (L-NAME), an eNOS inhibitor, reversed the decreased blood pressure and recovered the kidney dysfunction induced by low-salt with candesartan. The increased TUNEL-positive cells, Bax/Bcl-2 and cleaved-caspase3 protein abundance was ameliorated by L-NAME in vivo. In vitro, sodium nitroprusside, a nitric oxide donor, can also increase Bax/Bcl-2 and cleaved-caspase3 protein level in HK-2 cell. Thus, low-salt diet combined with candesartan in nephritis rats led to AKI, and the mechanism involved the increase of eNOS/NO, which linked to the decrease of blood pressure and the increase of apoptosis. This study provides practical guidance for salt intake in cases of RAS inhibitor usage clinically.


Assuntos
Injúria Renal Aguda , Nefrite , Ratos , Animais , Rim , NG-Nitroarginina Metil Éster/farmacologia , Dieta Hipossódica , Óxido Nítrico/metabolismo , Antagonistas de Receptores de Angiotensina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteína X Associada a bcl-2/metabolismo , Ratos Sprague-Dawley , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Pressão Sanguínea , Óxido Nítrico Sintase/metabolismo , Cloreto de Sódio , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Nefrite/metabolismo
17.
Materials (Basel) ; 16(3)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36770172

RESUMO

Composite material uses ceramic reinforcement to add to the metal matrix to obtain higher material properties. Structural design is an important direction of composite research. The reinforcement distribution of the core-shell structure has the unique advantages of strong continuity and uniform stress distribution. In this paper, a method of preparing boron carbide (B4C)-coated titanium (Ti) powder particles by ball milling and preparing core-shell B4C-reinforced Ti matrix composites by Spark Plasma Sintering was proposed. It can be seen that B4C coated on the surface of the spherical Ti powder to form a shell structure, and B4C had a certain continuity. Through X-ray diffraction characterization, it was found that B4C reacted with Ti to form layered phases of titanium boride (TiB) and titanium carbide (TiC). The compressive strength of the composite reached 1529.1 MPa, while maintaining a compressive strain rate of 5%. At the same time, conductivity and thermal conductivity were also characterized. The preparation process of the core-shell structure composites proposed in this paper has high feasibility and universality, and it is expected to be applied to other ceramic reinforcements. This result provides a reference for the design, preparation and performance research of core-shell composite materials.

18.
Ecotoxicol Environ Saf ; 249: 114391, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36508843

RESUMO

Barley is a diagnostic plant that often used in the research of soil pollution by heavy metals, our research explored the detoxification and tolerance mechanism of cadmium(Cd) in barley through pot experiment. We investigated subcellular distribution, chemical forms and oxidative damage of Cd in barley leaves, combing with the transmission electron microscopy and Fourier-transform infrared spectroscopy(FT-IR) to further understand the translocation, transformation characteristics and toxic effect of Cd in cells. The results showed that, the bioaccumulation factors in roots and shoots of barley were ranged of 4.03-7.48 and 0.51-1.30, respectively. Barley reduces the toxic effects by storing Cd in the roots and reducing its transport to the shoots. Compared to the control treatment (0 mg/kg), the percentage of Cd in the cell wall fractions of leaves in 300 mg/kg Cd treatment increased from 34.74 % to 38.41 %; the percentage of the organelle fractions increased from 24.47 % to 56.02 %; and the percentage of soluble fraction decreased from 40.80 % to 5.57 %. We found that 69.13 % of the highly toxic inorganic Cd and water-soluble Cd were converted to less toxic pectates and protein-integrated Cd (50.20 %) and undissolved Cd phosphates (18.93 %). This conversion of Cd was mainly due to its combination with -OH, -NH, -CN, -C-O-C, and -C-O-P groups. Excessive Cd induced a significant (P < 0.05) increase in the levels of peroxidase, malondialdehyde, and cell membrane permeability, which damaged the cell membrane and allowed Cd to enter the organelles. The chloroplasts and mitochondria were destroyed, and eventually the metabolism of intracellular substances was affected, resulting in symptoms of toxicity. Our research provides cellular-scale insight into the mechanisms of Cd tolerance in barley.


Assuntos
Hordeum , Poluentes do Solo , Hordeum/metabolismo , Cádmio/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Raízes de Plantas/metabolismo , Folhas de Planta/metabolismo , Poluentes do Solo/análise
19.
Materials (Basel) ; 15(23)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36499979

RESUMO

In the present study, the effects of SiC nanowires (SiCnws) with diameters of 100 nm, 250 nm and 450 nm on the microstructure and mechanical behavior of 20 vol.% SiCnws/6061Al composites prepared by pressure infiltration were studied. It was found that the interface between SiCnws and Al matrix was well bonded, and no interface product was found. The thicker SiCnws are beneficial to improve the density. In addition, the bamboo-like and bone-like morphologies of SiCnws produce a strong interlocking effect between SiCnws and Al, which helps to improve the strength and plasticity of the material. The tensile strength of the composite prepared by SiCnws with a diameter of 450 nm reached 544 MPa. With a decrease in the diameter of SiCnws, the strengthening effect of SiCnws increases. The yield strength of SiCnws/6061Al composites prepared by 100 nm is 13.4% and 28.5% higher than that of 250 nm and 450 nm, respectively. This shows that, in nano-reinforced composites, the small-size reinforcement has an excellent improvement effect on the properties of the composites. This result has a guiding effect on the subsequent composite structure design.

20.
Materials (Basel) ; 15(24)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36556875

RESUMO

The mechanical properties of (Ti, Nb)B/Ti2AlNb composites were expected to improve further by utilizing spark plasma sintering (SPS) and inducing the novel three-dimensional network architecture. In this study, (Ti, Nb)B/Ti2AlNb composites with the novel architecture were successfully fabricated by ball milling the LaB6 and Ti2AlNb mixed powders and subsequent SPS consolidation. The influence of the (Ti, Nb)B content on the microstructure and mechanical properties of the composites was revealed by using the scanning electron microscope (SEM), transmission electron microscopy (TEM) and electronic universal testing machine. The microstructural characterization demonstrated that the boride crystallized into a B27 structure and the α2-precipitated amount increased with the (Ti, Nb)B increasing. When the (Ti, Nb)B content reached 4.9 vol%, both the α2 and reinforcement exhibited a continuous distribution along the prior particle boundaries (PPBs). The tensile test displayed that the tensile strength of the composites presented an increasing trend with the increasing (Ti, Nb)B content followed by a decreasing trend. The composite with a 3.2 vol% reinforcement had the optimal mechanical properties; the yield strengths of the composite at 25 and 650 °C were 998.3 and 774.9 MPa, showing an 11.8% and 9.2% improvement when compared with the Ti2AlNb-based alloy. Overall, (Ti, Nb)B possessed an excellent strengthening effect and inhibited the strength weakening of the PPBs area at high temperatures; the reinforcement content mainly affected the mechanical properties of the (Ti, Nb)B/Ti2AlNb composites by altering the α2-precipitated amount and the morphology of (Ti, Nb)B in the PPBs area. Both the continuous precipitation of the brittle α2 phase and the agglomeration of the (Ti, Nb)B reinforcement dramatically deteriorated the mechanical properties.

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