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1.
FASEB J ; 38(6): e23564, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38522019

RESUMEN

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.


Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Quinasa Syk , Animales , Humanos , Ratones , Apoptosis , Nefropatías Diabéticas/genética , Metilación de ADN , Glucosa , Estrés Oxidativo , Transducción de Señal , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src/genética , Ratones Noqueados para ApoE , Quinasa Syk/genética
2.
Small ; 20(26): e2310387, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38312084

RESUMEN

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.
Analyst ; 149(6): 1766-1773, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38372348

RESUMEN

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.


Asunto(s)
Carbohidratos , Polisacáridos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Reproducibilidad de los Resultados
4.
J Phys Chem A ; 128(17): 3351-3360, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38651288

RESUMEN

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.

5.
J Chem Phys ; 160(16)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38661196

RESUMEN

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.

6.
BMC Med Inform Decis Mak ; 24(1): 77, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38500135

RESUMEN

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.


Asunto(s)
Aprendizaje Profundo , Agitación Psicomotora , Humanos , Agitación Psicomotora/diagnóstico , Inteligencia Artificial , Unidades de Cuidados Intensivos , Cuidados Críticos
7.
Ren Fail ; 46(2): 2369701, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38952279

RESUMEN

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.


Asunto(s)
Enfermedades Cardiovasculares , LDL-Colesterol , Nefropatías Diabéticas , Fallo Renal Crónico , Humanos , Masculino , Femenino , Persona de Mediana Edad , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/mortalidad , Nefropatías Diabéticas/sangre , LDL-Colesterol/sangre , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/sangre , China/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Factores de Riesgo , Anciano , Encuestas Nutricionales , Adulto , Incidencia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/sangre
8.
Int Wound J ; 21(4): e14852, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38584310

RESUMEN

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.


Asunto(s)
Magnetoterapia , Úlcera Varicosa , Humanos , Úlcera Varicosa/terapia , Lista de Verificación
9.
Entropy (Basel) ; 26(1)2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38248198

RESUMEN

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.

10.
Angew Chem Int Ed Engl ; 63(16): e202318589, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38385612

RESUMEN

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.

11.
Biochem Biophys Res Commun ; 664: 142-151, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-37167707

RESUMEN

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.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Podocitos , Ratones , Animales , Liraglutida/farmacología , Liraglutida/uso terapéutico , Diabetes Mellitus Tipo 2/metabolismo , Receptor del Péptido 1 Similar al Glucagón/agonistas , Podocitos/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Incretinas , Tejido Adiposo Blanco/metabolismo , Apoptosis
12.
Small ; 19(15): e2206865, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36634977

RESUMEN

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.

13.
Small ; 19(26): e2302295, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37194952

RESUMEN

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.

14.
Langmuir ; 39(29): 10079-10087, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37429037

RESUMEN

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).

15.
Langmuir ; 39(41): 14550-14561, 2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37782748

RESUMEN

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.

16.
J Med Genet ; 59(6): 579-588, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-33888552

RESUMEN

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.


Asunto(s)
Menopausia Prematura , Insuficiencia Ovárica Primaria , Animales , Femenino , Haploinsuficiencia/genética , Heterocigoto , Humanos , Ratones , Insuficiencia Ovárica Primaria/genética , Secuenciación del Exoma
17.
Ren Fail ; 45(1): 2158102, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36820611

RESUMEN

AIMS: Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease (ESKD). The identification of risk factors involved in the progression of DKD to ESKD is expected to result in early detection and appropriate intervention and improve prognosis. This study aimed to explore whether plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with kidney outcomes in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DKD. METHODS: Patients with biopsy-proven DKD who were followed up at West China Hospital over 12 months were enrolled. The kidney outcome was defined as progression to ESKD. The cutoff value of plasma NT-proBNP concentration was calculated by using receiver operating characteristic (ROC) curve analysis. The influence of NT-proBNP levels on kidney outcome in patients with DKD was assessed using Cox regression analysis. RESULTS: A total of 30 (24.5%) patients reached ESKD during a median follow-up of 24.1 months. The baseline serum NT-proBNP level had a significant correlation with baseline proteinuria, kidney function, glomerular lesions, interstitial fibrosis tubular atrophy (IFTA), and arteriolar hyalinosis. Multivariate Cox regression analysis indicated that increased NT-proBNP level was significantly associated with a higher risk of progression to ESKD (HR 6.43; 95% CI (1.65-25.10, p = 0.007), and each 1 SD increase in LG (NT-proBNP) was also associated with a higher risk (HR 2.43; 95% CI 1.94-5.29, p = 0.047) of an adverse kidney outcome after adjusting for confounding factors. CONCLUSIONS: A higher level of plasma NT-proBNP predicts kidney prognosis in patients with biopsy-proven DKD. This warrants further investigation into the potential mechanisms.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Fallo Renal Crónico , Humanos , Péptido Natriurético Encefálico , Pronóstico , Fragmentos de Péptidos , Biomarcadores , Progresión de la Enfermedad
18.
Sensors (Basel) ; 23(4)2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36850875

RESUMEN

Mobile crowdsensing (MCS) has been an emerging sensing paradigm in recent years, which uses a sensing platform for real-time processing to support various services for the Internet of Things (IoT) and promote the development of IoT. As an important component of MCS, how to design task assignment algorithms to cope with the coexistence of multiple concurrent heterogeneous tasks in group-oriented social relationships while satisfying the impact of users' preferences on heterogeneous multitask assignment and solving the preference matching problem under heterogeneous tasks, is one of the most pressing issues. In this paper, a new algorithm, group-oriented adjustable bidding task assignment (GO-ABTA), is considered to solve the group-oriented bilateral preference-matching problem. First, the initial leaders and their collaborative groups in the social network are selected by group-oriented collaboration, and then the preference assignment of task requesters and users is modeled as a stable preference-matching problem. Then, a tunable bidding task assignment process is completed based on preference matching under budget constraints. Finally, the individual reasonableness, stability, and convergence of the proposed algorithm are demonstrated. The effectiveness of the proposed algorithm and its superiority to other algorithms are verified by simulation results.

19.
Sensors (Basel) ; 23(17)2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37687881

RESUMEN

Spectrum sensing in Cognitive radio (CR) is a way to improve spectrum utilization by detecting spectral holes to achieve a dynamic allocation of spectrum resources. As it is often difficult to obtain accurate wireless environment information in real-world scenarios, the detection performance is limited. Signal-to-noise ratio (SNR), noise variance, and channel prior occupancy rate are critical parameters in wireless spectrum sensing. However, obtaining these parameter values in advance is challenging in practical scenarios. A lifting wavelet-assisted Expectation-Maximization (EM) joint estimation and detection method is proposed to estimate multiple parameters and achieve full-blind detection, which uses lifting wavelet in noise variance estimation to improve detection probability and convergence speed. Moreover, a stream learning strategy is used in estimating SNR and channel prior occupancy rate to fit the scenario where the SU has mobility. The simulation results demonstrate that the proposed method can achieve comparable detection performance to the semi-blind EM method.

20.
Sensors (Basel) ; 23(11)2023 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-37299740

RESUMEN

Pilot contamination due to pilot reuse seriously mitigates the performance of the cell-free massive multiple-input multiple-output (MIMO) systems. In this paper, we propose a joint pilot assignment scheme that employs user clustering and graph coloring (UC-GC) to reduce pilot contamination. The proposed method consists of two steps: firstly, we utilize AP selection to classify all users; secondly, we assign pilots to users with more severe pilot contamination using the graph coloring algorithm and then assign pilots to the remaining users. The numerical simulation results show that the proposed scheme outperforms existing pilot assignment schemes and significantly improves throughout with low complexity.


Asunto(s)
Algoritmos , Contaminación de Medicamentos , Análisis por Conglomerados , Simulación por Computador
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