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1.
FASEB J ; 38(6): e23564, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38522019

RESUMO

Epigenetic alterations, especially DNA methylation, have been shown to play a role in the pathogenesis of diabetes mellitus (DM) and its complications, including diabetic kidney disease (DKD). Spleen tyrosine kinase (Syk) is known to be involved in immune and inflammatory disorders. We, therefore, investigated the possible involvement of Syk promoter methylation in DKD, and the mechanisms underlying this process. Kidney tissues were obtained from renal biopsies of patients with early and advanced DKD. A diabetic mouse model (ApoE-/- DM) was generated from ApoE knockout (ApoE-/-) mice using a high-fat and high-glucose diet combined with low-dose streptozocin intraperitoneal injection. We also established an in vitro model using HK2 cells. A marked elevation in the expression levels of Syk, PKCß, and P66shc in renal tubules was observed in patients with DKD. In ApoE-/- DM mice, Syk expression and the binding of Sp1 to the Syk gene promoter were both increased in the kidney. In addition, the promoter region of the Syk gene exhibited hypomethylation. Syk inhibitor (R788) intervention improved renal function and alleviated pathologic changes in ApoE-/- DM mice. Moreover, R788 intervention alleviated oxidative stress and apoptosis and downregulated the expression of PKCß/P66shc signaling pathway proteins. In HK2 cells, oxLDL combined with high-glucose stimulation upregulated Sp1 expression in the nucleus (compared with control and oxLDL groups), and this was accompanied by an increase in the binding of Sp1 to the Syk gene promoter. SP1 silencing downregulated the expression of Syk and inhibited the production of reactive oxygen species and cell apoptosis. Finally, PKC agonist intervention reversed the oxidative stress and apoptosis induced by Syk inhibitor (R406). In DKD, hypomethylation at the Syk gene promoter was accompanied by an increase in Sp1 binding at the promoter. As a consequence of this enhanced Sp1 binding, Syk gene expression was upregulated. Syk inhibitors could attenuate DKD-associated oxidative stress and apoptosis via downregulation of PKCß/P66shc signaling pathway proteins. Together, our results identify Syk as a promising target for intervention in DKD.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Quinase Syk , Animais , Humanos , Camundongos , Apoptose , Nefropatias Diabéticas/genética , Metilação de DNA , Glucose , Estresse Oxidativo , Transdução de Sinais , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/genética , Camundongos Knockout para ApoE , Quinase Syk/genética
2.
Small ; 20(26): e2310387, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38312084

RESUMO

Rational design of heterostructure catalysts through phase engineering strategy plays a critical role in heightening the electrocatalytic performance of catalysts. Herein, a novel amorphous/crystalline (a/c) heterostructure (a-CoS/Ni3S2) is manufactured by a facile hydrothermal sulfurization method. Strikingly, the interface coupling between amorphous phase (a-CoS) and crystalline phase (Ni3S2) in a-CoS/Ni3S2 is much stronger than that between crystalline phase (c-CoS) and crystalline phase (Ni3S2) in crystalline/crystalline (c/c) heterostructure (c-CoS/Ni3S2) as control sample, which makes the meta-stable amorphous structure more stable. Meanwhile, a-CoS/Ni3S2 has more S vacancies (Sv) than c-CoS/Ni3S2 because of the presence of an amorphous phase. Eventually, for the oxygen evolution reaction (OER), the a-CoS/Ni3S2 exhibits a significantly lower overpotential of 192 mV at 10 mA cm-2 compared to the c-CoS/Ni3S2 (242 mV). An exceptionally low cell voltage of 1.51 V is required to achieve a current density of 50 mA cm-2 for overall water splitting in the assembled cell (a-CoS/Ni3S2 || Pt/C). Theoretical calculations reveal that more charges transfer from a-CoS to Ni3S2 in a-CoS/Ni3S2 than in c-CoS/Ni3S2, which promotes the enhancement of OER activity. This work will bring into play a fabrication strategy of a/c catalysts and the understanding of the catalytic mechanism of a/c heterostructures.

3.
Diabetes Obes Metab ; 26(10): 4241-4250, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39021330

RESUMO

AIM: To evaluate the impact of non-alcoholic fatty liver disease (NAFLD) presence and fibrosis risk on adverse outcomes in patients with type 2 diabetes and chronic kidney disease. METHODS: Data were sourced from two longitudinal cohorts: 1172 patients from the National Health and Nutrition Examination Survey (NHANES) and 326 patients from the kidney biopsy cohort at the West China Hospital of Sichuan University. Cox regression estimated hazard ratios (HRs) for NAFLD and liver fibrosis concerning adverse clinical outcomes. Subsequently, a two-sample Mendelian randomization study using genome-wide association study statistics explored NAFLD's potential causal link to cardio-cerebrovascular events. RESULTS: In the NHANES cohort, NAFLD stood as an independent risk factor for various outcomes: overall mortality [HR 1.53 (95% confidence interval, CI 1.21-1.95)], mortality because of cardio-cerebrovascular diseases [HR 1.63 (95% CI 1.12-2.37)], heart disease [HR 1.58 (95% CI 1.00-2.49)], and cerebrovascular disease [HR 3.95 (95% CI 1.48-10.55)]. Notably, advanced liver fibrosis, identified by a fibrosis-4 (FIB-4) score >2.67, exhibited associations with overall mortality, cardio-cerebrovascular disease mortality and heart disease mortality. Within the kidney biopsy cohort, NAFLD correlated with future end-stage kidney disease [ESKD; HR 2.17 (95% CI 1.41-3.34)], while elevated FIB-4 or NAFLD Fibrosis Scores predicted future ESKD, following full adjustment. Liver fibrosis was positively correlated with renal interstitial fibrosis and tubular atrophy in biopsies. Further Mendelian randomization analysis supported a causal relationship between NAFLD and cardio-cerebrovascular events. CONCLUSIONS: In patients with type 2 diabetes and chronic kidney disease, the NAFLD presence and elevated FIB-4 scores link to heightened mortality risk and ESKD susceptibility. Moreover, NAFLD shows a causal relationship with cardio-cerebrovascular events.


Assuntos
Diabetes Mellitus Tipo 2 , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Insuficiência Renal Crônica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/mortalidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Longitudinais , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/mortalidade , Cirrose Hepática/mortalidade , Cirrose Hepática/complicações , Cirrose Hepática/patologia , China/epidemiologia , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/complicações , Fatores de Risco , Análise da Randomização Mendeliana , Inquéritos Nutricionais , Adulto , Idoso , Estudos de Coortes , Estudo de Associação Genômica Ampla
4.
Analyst ; 149(6): 1766-1773, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38372348

RESUMO

Quantitative carbohydrate analysis faces challenges in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), including insufficient sensitivity and inconsistent spatial distribution of ion intensity. This study introduces an innovative sample preparation approach, the Rapidly Freeze-Drying Droplet (RFDD) method, aimed at overcoming these challenges by enhancing the homogeneity of the sample morphology and signal intensity in MALDI. Compared to conventional preparation methods, the RFDD method reduces the laser energy threshold and demonstrates a remarkable increase in signal intensity for carbohydrates, facilitating the detection of high-molecular-weight polysaccharides (>10 kDa). The RFDD-prepared samples exhibit a uniformly distributed signal intensity that overcomes the 'sweet spot' issue in MALDI. The enhanced signal intensity and reproducibility lead to reliable quantitative analysis of carbohydrates, eliminating the need for expensive isotopic standards in each sample. A straightforward and accessible approach is presented for general laboratories, revolutionizing carbohydrate analysis in MALDI-MS.


Assuntos
Carboidratos , Polissacarídeos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Reprodutibilidade dos Testes
5.
Cost Eff Resour Alloc ; 22(1): 71, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334364

RESUMO

METHODS: Web of Science, Cochrane library and PubMed were systematically searched up to January 2024 to identify studies examining the impact of financial incentives on diabetes management in patients. Studies were evaluated based on the robustness of their methodology, participant numbers, and quality scores. The Cochrane risk-of-bias tool was applied for randomized controlled trials, while the Newcastle-Ottawa Scale was used for non-randomized controlled trials to assess study quality. Due to the heterogeneity of the included studies, a narrative synthesis approach was utilized. RESULTS: In the study, we included 12 published research studies. Five studies investigated the influence of financial incentives on patient behavior, all demonstrating a significant positive impact on behaviors such as blood glucose monitoring, medication adherence, and physical activity. 10 studies analyzed the impact of financial incentives on HbA1c levels in diabetes patients. Among them, 5 studies reported that financial incentives could improve HbA1c levels through longitudinal historical comparisons. The other 5 studies did not find significant improvements compared to the control group. Three studies explored long-term effects, two studies targeting the adolescent population had no impact, and one study targeting adults had a positive impact. CONCLUSIONS: In summary, this review found that financial incentives can positively influence patient behavior and enhance compliance, but their impact on HbA1c levels is inconsistent. Financial incentives may help adult patients maintain behavior even after the withdrawal of incentives.

6.
J Phys Chem A ; 128(17): 3351-3360, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38651288

RESUMO

H2S is being detected in the atmospheres of ever more interstellar bodies, and photolysis is an important mechanism by which it is processed. Here, we report H Rydberg atom time-of-flight measurements following the excitation of H2S molecules to selected rotational (JKaKc') levels of the 1B1 Rydberg state associated with the strong absorption feature at wavelengths of λ ∼ 129.1 nm. Analysis of the total kinetic energy release spectra derived from these data reveals that all levels predissociate to yield H atoms in conjunction with both SH(A) and SH(X) partners and that the primary SH(A)/SH(X) product branching ratio increases steeply with ⟨Jb2⟩, the square of the rotational angular momentum about the b-inertial axis in the excited state. These products arise via competing homogeneous (vibronic) and heterogeneous (Coriolis-induced) predissociation pathways that involve coupling to dissociative potential energy surfaces (PES(s)) of, respectively, 1A″ and 1A' symmetries. The present data also show H + SH(A) product formation when exciting the JKaKc' = 000 and 111 levels, for which ⟨Jb2⟩ = 0 and Coriolis coupling to the 1A' PES(s) is symmetry forbidden, implying the operation of another, hitherto unrecognized, route to forming H + SH(A) products following excitation of H2S at energies above ∼9 eV. These data can be expected to stimulate future ab initio molecular dynamic studies that test, refine, and define the currently inferred predissociation pathways available to photoexcited H2S molecules.

7.
J Phys Chem A ; 128(38): 8111-8122, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39283291

RESUMO

The first high-resolution translational spectroscopy studies of D atom photoproducts following excitation to the Rydberg states of D2S are reported. Excitation at wavelengths λ ∼ 139.1 nm reveals an unusual 'inverse' isotope effect; the 1B1(3da1←2b1) Rydberg state of D2S predissociates much faster than its counterpart in H2S. This is attributed to accidental near resonance with a vibrationally excited level of a lower-lying, more heavily predissociated Rydberg state of D2S that boosts the probability of nonadiabatic coupling to the dissociation continuum with 1A″ symmetry. Excitation at λ ∼ 129.1 nm populates the 1B1(4da1←2b1) Rydberg state, which predissociates more slowly and allows the study of ways in which the branching into different quantum states of the SD products varies with the choice of parent excited (JKaKc) level. All excited parent levels yield both ground (X) and electronically excited (A) state SD fragments. The former are distributed over a wide range of rovibrational (v″, N″) levels, while the population of levels with low v' and high N' is favored in the latter. These trends reflect the topographies of the dissociative 1A″ (1A') potential energy surfaces that correlate with the respective dissociation limits. Rotational motion about the b-inertial axis in the excited state molecule increases the relative yield of SD(A) products, consistent with dissociation by rotationally (Coriolis-) induced coupling from the photoexcited Rydberg level to the 1A' continuum. Molecules excited to the rotationless (JKaKc = 000) level also yield some SD(A) products, however, confirming the operation of a rival fragmentation pathway wherein photoexcited molecules decay by initial vibronic coupling to the 1A″ continuum, with subsequent nonadiabatic coupling between the 1A″ and 1A' continua enabling access to the D + SD(A) limit.

8.
Environ Res ; 262(Pt 2): 119943, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39276835

RESUMO

Understanding polychlorinated biphenyl (PCB) degradation in sequential anaerobic-aerobic remediation is crucial for effective remediation strategies. In this study, microcosm and greenhouse experiments were conducted to dissect the effects of organic amendments (carbon-based) and plant treatments (ryegrass) on soil PCB dissipation under oxic and sequential anoxic-oxic conditions. We analyzed the soil bacterial community in greenhouse experiments using high-throughput sequencing to explore plant-pollutant-microbe interactions. Microcosm results showed that organic amendments alone did not facilitate aerobic PCB removal, but significantly accelerated PCB dechlorination under anoxic conditions altering the profiles of PCB congeners. In standard greenhouses, plant treatments substantially increased PCB dissipation to 50.8 ± 3.9%, while organic amendments aided phytoremediation by promoting plant growth, increasing PCB removal to 65.9 ± 3.2%. In sequential anaerobic-aerobic greenhouses, plant growth was inhibited by flooding treatment while flooding stress was markedly alleviated by organic amendments. Plant treatments alone during sequential treatments did not lead to PCB dissipation; however, dissipation was significantly promoted following organic amendments, achieving a removal of 41.2 ± 5.7%. This PCB removal was primarily due to anaerobic dechlorination during flooding (27.8 ± 0.5% removal), rather than from plant growth stimulation in subsequent planting phase. Co-occurrence network and functional prediction analyses revealed that organic amendments recruited specific bacterial clusters with distinct functions under different conditions, especially stimulating plant-microbe interactions and xenobiotics biodegradation pathways in planted systems. The findings provide valuable guidance for the design of practical remediation strategies under various remedy scenarios, such as in arable or paddy fields.

9.
J Chem Phys ; 160(16)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38661196

RESUMO

Produced by both nature and human activities, sulfur dioxide (SO2) is an important species in the earth's atmosphere. SO2 has also been found in the atmospheres of other planets and satellites in the solar system. The photoabsorption cross sections and photodissociation of SO2 have been studied for several decades. In this paper, we reported the experimental results for photodissociation dynamics of SO2 via the G̃1B1 state. By analyzing the images from the time-sliced velocity map ion imaging method, the vibrational state population distributions and anisotropy parameters were obtained for the O(1D2) + SO(X3Σ-, a1Δ, b1Σ+) and O(1S0) + SO(X3Σ-) channels, and the branching ratios for the channels O(1D2) + SO(X3Σ-), O(1D2) + SO(a1Δ), and O(1D2) + SO(b1Σ+) were determined to be ∼0.3, ∼0.6, and ∼0.1, respectively. The SO products were dominant in electronically and rovibrationally excited states, which may have yet unrecognized roles in the upper planetary atmosphere.

10.
BMC Med Inform Decis Mak ; 24(1): 77, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500135

RESUMO

OBJECTIVE: To address the challenge of assessing sedation status in critically ill patients in the intensive care unit (ICU), we aimed to develop a non-contact automatic classifier of agitation using artificial intelligence and deep learning. METHODS: We collected the video recordings of ICU patients and cut them into 30-second (30-s) and 2-second (2-s) segments. All of the segments were annotated with the status of agitation as "Attention" and "Non-attention". After transforming the video segments into movement quantification, we constructed the models of agitation classifiers with Threshold, Random Forest, and LSTM and evaluated their performances. RESULTS: The video recording segmentation yielded 427 30-s and 6405 2-s segments from 61 patients for model construction. The LSTM model achieved remarkable accuracy (ACC 0.92, AUC 0.91), outperforming other methods. CONCLUSION: Our study proposes an advanced monitoring system combining LSTM and image processing to ensure mild patient sedation in ICU care. LSTM proves to be the optimal choice for accurate monitoring. Future efforts should prioritize expanding data collection and enhancing system integration for practical application.


Assuntos
Aprendizado Profundo , Agitação Psicomotora , Humanos , Agitação Psicomotora/diagnóstico , Inteligência Artificial , Unidades de Terapia Intensiva , Cuidados Críticos
11.
Ren Fail ; 46(2): 2369701, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38952279

RESUMO

AIMS: This study aimed to investigate the correlations between estimated small dense low-density lipoprotein-cholesterol (esd-LDL-c) and the development of end-stage kidney disease (ESKD), cardiovascular mortality, and all-cause mortality in individuals with diabetic kidney disease (DKD) or diabetes mellitus (DM) concomitant chronic kidney disease (CKD). METHODS: We analyzed the data from a biopsy-proven DKD cohort conducted at West China Hospital of Sichuan University between 2009 and 2021 (the DKD cohort) and participants with DM and CKD in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 (the NHANES DM-CKD cohort). Cox regression analysis was also used to estimate associations between esd-LDL-c and the incidence of ESKD, cardiovascular mortality, and all-cause mortality. RESULTS: There were 175 ESKD events among 338 participants in the DKD cohort. Patients were divided into three groups based on esd-LDL-c tertiles (T1 < 33.7 mg/dL, T2 ≥ 33.7 mg/dL to <45.9 mg/dL, T3 ≥ 45.9 mg/dL). The highest tertile of esd-LDL-c was associated with ESKD (adjusted HR 2.016, 95% CI 1.144-3.554, p = .015). Furthermore, there were 99 deaths (39 cardiovascular) among 293 participants in the NHANES DM-CKD cohort. Participants were classified into three groups in line with the tertile values of esd-LDL-c in the DKD cohort. The highest tertile of esd-LDL-c was associated with cardiovascular mortality (adjusted HR 3.95, 95% CI 1.3-12, p = .016) and all-cause mortality (adjusted HR 2.37, 95% CI 1.06-5.32, p = .036). CONCLUSIONS: Higher esd-LDL-c was associated with increased risk of ESKD in people with biopsy-proven DKD, and higher cardiovascular and all-cause mortality risk among those with DM-CKD.


Assuntos
Doenças Cardiovasculares , LDL-Colesterol , Nefropatias Diabéticas , Falência Renal Crônica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/sangue , LDL-Colesterol/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Falência Renal Crônica/sangue , China/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Fatores de Risco , Idoso , Inquéritos Nutricionais , Adulto , Incidência , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/sangue
12.
Int Wound J ; 21(4): e14852, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38584310

RESUMO

This study aims to evaluate the effects of electromagnetic therapy (EMT) on the treatment of venous leg ulcers (VLUs) by synthesising and appraising available meta-analyses (MAs) and systematic reviews (SRs). A comprehensive literature search was conducted across major databases up to 10 January 2024, focusing on SRs/MAs that investigated the use of EMT for VLUs. Selection criteria followed the PICO framework, and dual-author extraction was used for accuracy. Quality assessment tools included AMSTAR2, ROBIS, PRISMA, and GRADE. The search yielded five eligible studies. The reviews collectively presented moderate methodological quality and a low risk of bias in several domains. Reporting quality was high, albeit with inconsistencies in fulfilling certain PRISMA checklist items. The evidence quality, primarily downgraded due to small sample sizes, was rated as moderate. Whilst some studies suggest potential benefits of EMT in the treatment of VLUs, the overall evidence is inconclusive due to methodological limitations and limited sample sizes. This review underscores the need for future research with more rigorous methodologies and larger cohorts to provide clearer insights into the efficacy of EMT for VLUs.


Assuntos
Magnetoterapia , Úlcera Varicosa , Humanos , Úlcera Varicosa/terapia , Lista de Checagem
13.
Entropy (Basel) ; 26(1)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38248198

RESUMO

The extremely harsh environment of the high temperature plasma imposes strict requirements on the construction materials of the first wall in a fusion reactor. In this work, a refractory alloy system, WTaVTiZrx, with low activation and high entropy, was theoretically designed based on semi-empirical formula and produced using a laser cladding method. The effects of Zr proportions on the metallographic microstructure, phase composition, and alloy chemistry of a high-entropy alloy cladding layer were investigated using a metallographic microscope, XRD (X-ray diffraction), SEM (scanning electron microscope), and EDS (energy dispersive spectrometer), respectively. The high-entropy alloys have a single-phase BCC structure, and the cladding layers exhibit a typical dendritic microstructure feature. The evolution of microstructure and mechanical properties of the high-entropy alloys, with respect to annealing temperature, was studied to reveal the performance stability of the alloy at a high temperature. The microstructure of the annealed samples at 900 °C for 5-10 h did not show significant changes compared to the as-cast samples, and the microhardness increased to 988.52 HV, which was higher than that of the as-cast samples (725.08 HV). When annealed at 1100 °C for 5 h, the microstructure remained unchanged, and the microhardness increased. However, after annealing for 10 h, black substances appeared in the microstructure, and the microhardness decreased, but it was still higher than the matrix. When annealed at 1200 °C for 5-10 h, the microhardness did not increase significantly compared to the as-cast samples, and after annealing for 10 h, the microhardness was even lower than that of the as-cast samples. The phase of the high entropy alloy did not change significantly after high-temperature annealing, indicating good phase stability at high temperatures. After annealing for 10 h, the microhardness was lower than that of the as-cast samples. The phase of the high entropy alloy remained unchanged after high-temperature annealing, demonstrating good phase stability at high temperatures.

14.
Angew Chem Int Ed Engl ; 63(16): e202318589, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38385612

RESUMO

Catalyst surface dynamics drive the generation of active species for electrocatalytic reactions. Yet, the understanding of dominant site formation and reaction mechanisms is limited. In this study, we thoroughly investigate the dynamic reconstruction of two-dimensional defective Bi nanosheets from exfoliated Bi2Se3 nanosheets under electrochemical CO2 and nitrate (NO3 -) reduction conditions. The ultrathin Bi2Se3 nanosheets obtained by NaBH4-assisted cryo-mediated liquid-phase exfoliation are more easily reduced and reconstructed to Bi nanosheets with high-density grain boundaries (GBs; GB-rich Bi). The reconstructed GB-rich Bi catalyst affords a remarkable yield rate of 4.6 mmol h-1 mgcat. -1 and Faradaic efficiency of 32 % for urea production at -0.40 V vs. RHE. Notably, this yield rate is 2 and 8.2 times higher than those of the low-GB Bi and bulk Bi catalysts, respectively. Theoretical analysis demonstrates that the GB sites significantly reduce the *CO and *NH2 intermediate formation energy and C-N coupling energy barrier, enabling selective urea electrosynthesis on the GB-rich Bi catalyst. This work will trigger further research into the structure-activity interplay in dynamic processes using in situ techniques.

15.
Biochem Biophys Res Commun ; 664: 142-151, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37167707

RESUMO

Glucagon like peptide-1 receptor agonists (GLP-1RAs) belong to the class of incretin drugs. Incretin is a hormone secreted into blood by intestinal cells after food stimulation that induces insulin secretion. Liraglutide is a long-acting GLP-1RA that can reduce blood pressure, blood lipids, and inflammation. Previous studies showed that liraglutide can promote white fat browning and improve renal outcomes in patients with type 2 diabetes mellitus. However, no studies have linked white fat browning to kidney damage. The objective of this study was to investigate the effects of liraglutide-induced white fat browning on podocyte apoptosis in diabetic nephropathy. We also aimed to determine whether podocytes express glucagon like peptide-1 receptor (GLP-1R) and if liraglutide directly affects podocytes via GLP-1R. We assessed fat and renal function in db/db and wild-type mice and the effects of adipocyte conditioned medium on cultured podocytes. Liraglutide (400 mg/kg/d) was subcutaneously injected for 8 weeks. Liraglutide promoted white fat browning in vivo. During adipogenic differentiation of 3T3-L1 cells in vitro, liraglutide also upregulated expression of peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC1α) and uncoupling protein 1 (UCP1), which can induce white fat browning in vitro. Furthermore, we found that supernatant from 3T3-L1 cells stimulated by liraglutide reduced podocyte apoptosis. The inhibitory effect of liraglutide on apoptosis was eliminated by exogenous TNF-α. Finally, podocytes express GLP-1R. In vivo and in vitro studies showed that the apoptosis of podocytes in diabetic nephropathy may be related to the effect of liraglutide on promoting white lipid browning. Similarly, liraglutide may directly affect podocytes via GLP-1R.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Podócitos , Camundongos , Animais , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Podócitos/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Incretinas , Tecido Adiposo Branco/metabolismo , Apoptose
16.
Small ; 19(15): e2206865, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36634977

RESUMO

Defect engineering for vacancies, holes, nano precipitates, dislocations, and strain are efficient means of suppressing lattice thermal conductivity. Multiple microstructural defects are successfully designed in Cu1- x Agx GaTe2 (0 ≤ x ≤ 0.5) solid solutions through high-ratio alloying and vibratory ball milling, to achieve ultra-low thermal conductivity and record-breaking thermoelectric performance. Extremely low total thermal conductivities of 1.28 W m-1  K-1 at 300 K and 0.40 W m-1  K-1 at 873 K for the Cu0.5 Ag0.5 GaTe2 are observed, which are ≈79% and ≈58% lower than that of the CuGaTe2 matrix. Multiple phonon scattering mechanisms are collectively responsible for the reduction of thermal conductivity in this work. On one hand, large amounts of nano precipitates and dislocations are formed via vibrating ball milling followed by the low-temperature hot press, which can enhance phonon scattering. On the other hand, the difference in atomic sizes, distorted chemical bonds, elements fluctuation, and strained domains are caused by the high substitution ratio of Ag and also function as a center for the strong phonon scattering. As a result, the Cu0.7 Ag0.3 GaTe2 exhibits a record high ZTmax of ≈1.73 at 873 K and ZTave of ≈0.69 between 300-873 K, which are the highest values of CuGaTe2 -based thermoelectric materials.

17.
Small ; 19(26): e2302295, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37194952

RESUMO

Although the electrocatalytic nitrate reduction reaction (NO3 - RR) is an attractive NH3 synthesis route, it suffers from low yield due to the lack of efficient catalysts. Here, this work reports a novel grain boundary (GB)-rich Sn-Cu catalyst, derived from in situ electroreduction of Sn-doped CuO nanoflower, for effectively electrochemical converting NO3 - to NH3 . The optimized Sn1% -Cu electrode achieves a high NH3 yield rate of 1.98 mmol h-1 cm-2 with an industrial-level current density of -425 mA cm-2 at -0.55 V versus a reversible hydrogen electrode (RHE) and a maximum Faradaic efficiency of 98.2% at -0.51 V versus RHE, outperforming the pure Cu electrode. In situ Raman and attenuated total reflection Fourier transform infrared spectroscopies reveal the reaction pathway of NO3 - RR to NH3 by monitoring the adsorption property of reaction intermediates. Density functional theory calculations clarify that the high-density GB active sites and the competitive hydrogen evolution reaction (HER) suppression induced by Sn doping synergistically promote highly active and selective NH3 synthesis from NO3 - RR. This work paves an avenue for efficient NH3 synthesis over Cu catalyst by in situ reconstruction of GB sites with heteroatom doping.

18.
Langmuir ; 39(29): 10079-10087, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37429037

RESUMO

Ni-Co-W is an alloy with excellent overall performance and wide application prospects. Electrochemical deposition of Ni-Co-W alloys is currently the most promising process for replacing hexavalent chromium plating. Variations in the W content of the Ni-Co-W coating significantly affect its surface morphology, internal structure, and mechanical properties. Considering the numerous defects with conventional electrochemical deposition, a laser was introduced to enhance the quality and rate of deposition. Using a multienergy composite field, the deposition technique enhanced various properties at room temperature. Ni-Co-W alloy coatings were fabricated through electrochemical deposition and laser electrochemical deposition using electrolytes containing Na2WO4·2H2O at concentrations of 12, 15, 18, and 24 g/L in this investigation. This study aimed to examine how laser irradiation strengthens the corrosion resistance of the coatings. The corrosion resistance could be enhanced with an initial W content increase, but the corrosion resistance did not depend entirely on the W content. Variations in the W content of the electrochemically deposited coatings affected the surface morphology, residual internal stresses, and crystal structure, changing the corrosion resistance. In contrast, the laser electrochemical deposition coating was caused by the combined effect of the W content and laser irradiation (concentration of <18 g/L). Laser electrochemical deposition of the Ni-Co-W coating resulted in a higher W content than electrochemical deposition (≥3.5%), improved the residual internal stresses, and refined the grain size of the coating, resulting in better corrosion resistance (corrosion rate decreased by 74% and Rct increased by 109.1% at most).

19.
Langmuir ; 39(41): 14550-14561, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37782748

RESUMO

The silver coating is widely used in electronic device manufacturing due to its excellent conductivity and soldering properties. Conventional preparation of local silver coating often uses the preplated silver, mask high-speed silver plating, and deplated silver processes. In this paper, the laser-induced electrodeposition technique is used to perform maskless laser-induced localized electrodeposition on a copper substrate preplated with a layer of silver. After the deplated silver process, ultrathin silver coatings with high dimensional accuracy, good corrosion resistance, and good bonding were obtained. The spatial distribution of the transient temperature field under laser irradiation is studied, the variation pattern of cathode substrate current under laser irradiation is tested, and finally, the spatial distribution of the pressure field under laser irradiation is simulated by Comsol. The effect of different laser scanning methods on the coating morphology was investigated, and the experimental study of the different single pulse energy-induced localized silver coatings was systematically carried out. The results show that the localized coating obtained by cross-line scanning with a laser single pulse energy of 93 µJ is flat with a film thickness of 0.23 µm, high dimensional accuracy, and good bonding force and corrosion resistance properties. This method provides a new approach for the preparation of a localized silver coating.

20.
J Med Genet ; 59(6): 579-588, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33888552

RESUMO

BACKGROUND: Premature ovarian insufficiency (POI) is a common disease in women that leads to a reduced reproductive lifespan. The aetiology of POI is genetically heterogeneous, with certain double-strand break (DSB) repair genes being implicated in POI. Although non-homologous end joining (NHEJ) is an efficient DSB repair pathway, the functional relationship between this pathway and POI remains unknown. METHODS AND RESULTS: We conducted whole-exome sequencing in a Chinese family and identified a rare heterozygous loss-of-function variant in non-homologous end joining factor 1 (NHEJ1): c.532C>T (p.R178*), which co-segregated with POI and irregular menstruation. The amount of NHEJ1 protein in the proband was half of the normal level, indicating a link between NHEJ1 haploinsufficiency and POI. Furthermore, another rare heterozygous NHEJ1 variant c.500A>G (p.Y167C) was identified in one of 100 sporadic POI cases. Both variants were predicted to be deleterious by multiple in silico tools. In vitro assays showed that knock-down of NHEJ1 in human KGN ovarian cells impaired DNA repair capacity. We also generated a knock-in mouse model with a heterozygous Nhej1 variant equivalent to NHEJ1 p.R178* in familial patients. Compared with wild-type mice, heterozygous Nhej1-mutated female mice required a longer time to first birth, and displayed reduced numbers of primordial and growing follicles. Moreover, these mice exhibited higher sensitivity to DSB-inducing drugs. All these phenotypes are analogous to the progressive loss of ovarian function observed in POI. CONCLUSIONS: Our observations in both humans and mice suggest that NHEJ1 haploinsufficiency is associated with non-syndromic POI, providing novel insights into genetic counselling and clinical prevention of POI.


Assuntos
Menopausa Precoce , Insuficiência Ovariana Primária , Animais , Feminino , Haploinsuficiência/genética , Heterozigoto , Humanos , Camundongos , Insuficiência Ovariana Primária/genética , Sequenciamento do Exoma
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