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DNA-PKcs is a key regulator of DNA double-strand break repair. Apart from its canonical role in the DNA damage response, DNA-PKcs is involved in the cellular response to oxidative stress (OS), but its exact role remains unclear. Here, we report that DNA-PKcs-deficient human cells display depolarized mitochondria membrane potential (MMP) and reoriented metabolism, supporting a role for DNA-PKcs in oxidative phosphorylation (OXPHOS). DNA-PKcs directly interacts with mitochondria proteins ANT2 and VDAC2, and formation of the DNA-PKcs/ANT2/VDAC2 (DAV) complex supports optimal exchange of ADP and ATP across mitochondrial membranes to energize the cell via OXPHOS and to maintain MMP. Moreover, we demonstrate that the DAV complex temporarily dissociates in response to oxidative stress to attenuate ADP-ATP exchange, a rate-limiting step for OXPHOS. Finally, we found that dissociation of the DAV complex is mediated by phosphorylation of DNA-PKcs at its Thr2609 cluster by ATM kinase. Based on these findings, we propose that the coordination between the DAV complex and ATM serves as a novel oxidative stress checkpoint to decrease ROS production from mitochondrial OXPHOS and to hasten cellular recovery from OS.
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Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ligação a DNA , Estresse Oxidativo , Humanos , Trifosfato de Adenosina/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Mitocôndrias/metabolismo , FosforilaçãoRESUMO
Type 1 diabetes (T1D) is an autoimmune disease caused by destruction of the pancreatic ß-cells. Genome-wide association (GWAS) and fine mapping studies have been conducted mainly in European ancestry (EUR) populations. We performed a multi-ancestry GWAS to identify SNPs and HLA alleles associated with T1D risk and age at onset. EUR families (N = 3223), and unrelated individuals of African (AFR, N = 891) and admixed (Hispanic/Latino) ancestry (AMR, N = 308) were genotyped using the Illumina HumanCoreExome BeadArray, with imputation to the TOPMed reference panel. The Multi-Ethnic HLA reference panel was utilized to impute HLA alleles and amino acid residues. Logistic mixed models (T1D risk) and frailty models (age at onset) were used for analysis. In GWAS meta-analysis, seven loci were associated with T1D risk at genome-wide significance: PTPN22, HLA-DQA1, IL2RA, RNLS, INS, IKZF4-RPS26-ERBB3, and SH2B3, with four associated with T1D age at onset (PTPN22, HLA-DQB1, INS, and ERBB3). AFR and AMR meta-analysis revealed NRP1 as associated with T1D risk and age at onset, although NRP1 variants were not associated in EUR ancestry. In contrast, the PTPN22 variant was significantly associated with risk only in EUR ancestry. HLA alleles and haplotypes most significantly associated with T1D risk in AFR and AMR ancestry differed from that seen in EUR ancestry; in addition, the HLA-DRB1*08:02-DQA1*04:01-DQB1*04:02 haplotype was 'protective' in AMR while HLA-DRB1*08:01-DQA1*04:01-DQB1*04:02 haplotype was 'risk' in EUR ancestry, differing only at HLA-DRB1*08. These results suggest that much larger sample sizes in non-EUR populations are required to capture novel loci associated with T1D risk.
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Diabetes Mellitus Tipo 1 , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Humanos , Diabetes Mellitus Tipo 1/genética , Masculino , Feminino , População Branca/genética , Idade de Início , Alelos , Cadeias alfa de HLA-DQ/genética , População Negra/genética , Criança , Hispânico ou Latino/genética , Antígenos HLA/genética , AdolescenteRESUMO
Mesenchymal stem cells (MSCs) reveal multifaceted immunoregulatory properties, which can be applied for diverse refractory and recurrent disease treatment including acute graft-versus-host disease (aGVHD). Distinguishing from MSCs with considerable challenges before clinical application, MSCs-derived exosomes (MSC-Exos) are cell-free microvesicles with therapeutic ingredients and serve as advantageous alternatives for ameliorating the outcomes of aGVHD. MSC-Exos were enriched and identified by western blotting analysis, NanoSight, and transmission electron microscopy (TEM). Bone marrow-derived MSCs (denoted as MSCs) and exosomes (denoted as MSC-Exos) were infused into the aGVHD SD-Wister rat model via tail vein, and variations in general growth and survival of rats were observed. The level of inflammatory factors in serum was quantized by enzyme-linked immunosorbent assay (ELISA). The pathological conditions of the liver and intestine of rats were observed by frozen sectioning. The ratios of CD4+/CD8+ and Treg cell proportions in peripheral blood, together with the autophagy in the spleen and thymus, were analyzed by flow cytometry. After treatment with MSC-Exos, the survival time of aGVHD rats was prolonged, the clinical manifestations of aGVHD in rats were improved, whereas the pathological damage of aGVHD in the liver and intestine was reduced. According to ELISA, we found that MSC-Exos revealed ameliorative effect upon aGVHD inflammation (e.g., TNF-α, IL-2, INF-γ, IL-4, and TGF-ß) compared to the MSC group. After MSC-Exo treatment, the ratio of Treg cells in peripheral blood was increased, whereas the ratio of CD4+/CD8+ in peripheral blood and the autophagy in the spleen and thymus was decreased. MSC-Exos effectively suppressed the activation of immune cells and the manifestation of the inflammatory response in the aGVHD rat model. Our data would supply new references for MSC-Exo-based "cell-free" biotherapy for aGVHD in future.
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Exossomos , Doença Enxerto-Hospedeiro , Células-Tronco Mesenquimais , Animais , Exossomos/metabolismo , Doença Enxerto-Hospedeiro/terapia , Ratos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Ratos Wistar , Masculino , Ratos Sprague-Dawley , Transplante de Células-Tronco Mesenquimais/métodos , Linfócitos T Reguladores/imunologia , Células da Medula Óssea/citologia , AutofagiaRESUMO
Hierarchical biobased micro/nanomaterials offer great potential as the next-generation building blocks for robust films or macroscopic fibers with high strength, while their capability in suppressing crack propagation when subject to damage is hindered by their limited length. Herein, we employed an approach to directly convert bulk wood into fibers with a high aspect ratio and nanosized branching structures. Particularly, the length of microfibers surpassed 1 mm with that of the nanosized branches reaching up to 300 µm. The presence of both interwoven micro- and nanofibers endowed the product with substantially improved tensile strength (393.99 MPa) and toughness (19.07 MJ m-3). The unique mechanical properties arose from mutual filling and the hierarchical deformation facilitated by branched nanofibers, which collectively contributed to effective energy dissipation. Hence, the nanotransformation strategy opens the door toward a facial, scalable method for building high-strength film or macroscopic fibers available in various advanced applications.
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The shrinkage and collapse of wood cell walls during carbonization make it challenging to control the size and shape of carbonized wood (CW) through pre- or postprocessing (e.g., sawing, cutting, and milling). Herein, a shape-adaptive MXene shell (MS) is created on the surface of the wood cell walls. The MS limits the deformation of wood cell walls by spatial confinement and traction effects, which is supported by the inherent dimensional stability of the MS and the formation of new C-O-Ti covalent bonds between the wood cell wall and MS. Consequently, the volumetric shrinkage ratio of CW encapsulated by the MS (CW-MS) is significantly reduced from 54.8% for CW to 2.6% for CW-MS even at 800 °C. The harnessing of this collapse enables the production of CW-MS with prolonged stability and high electric conductivity (384 S m-1). These properties make CW-MS suitable for energy storage devices with various designed shapes, matching the increasingly compact and complex structures of electronic devices.
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Assembling active materials into dense electrodes is a promising way to obtain high-volumetric-capacitance supercapacitors, but insufficient ion channels in the dense structure lead to a low rate capability. Herein, a dense and robust wood electrode with a large MXene volumetric mass loading (1.25 g cm-3) and abundant ion diffusion channels is designed via a facile capillary-force-driven self-densification strategy. Specifically, MXene is assembled onto a wood cell wall, endowing the wood electrode with good electrical conductivity (86 S cm-1) and high electrochemical activity (5.9 F cm-2 at 1 mA cm-2). Notably, the oriented channels along with spaces between adjacent microfibrils recast after densification ensure efficient ion transport for the wood electrode, achieving an excellent rate capability with a high capacitance retention of 77% from 1 to 20 mA cm-2. Meanwhile, the capillary force induces self-densification on the softened wood cell wall, resulting in a highly compact and robust structure for the wood electrode.
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Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.
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População Negra/genética , Estatura/genética , Estudo de Associação Genômica Ampla , África/etnologia , Negro ou Afro-Americano/genética , Europa (Continente)/etnologia , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Copper iodide organic-inorganic hybrid materials have been favored by many researchers in the field of solid-state lighting (SSL) due to their structural diversity and optical adjustability. In this paper, three isomeric copper iodide cluster hybrid materials, Cu4I6(L)2(1), Cu5I4.5Cl2.5(L)2(2) and Cu5I7(L)2) (3) (L=1-(4-methylpyrimidin-2-yl)-1,4-diazabicyclo[2.2.2]octan-1-ium), were achieved by adjusting the reaction conditions. The crystal color transit from green, yellow to orange and the internal quantum yield (IQY) increase from 57 %-88 %. All three complexes have good thermal stability, good solution processability, and high quantum yield. And origin and mechanism of luminescence of complexes were further studied. This study can provide ideas and theoretical basis for the regulation of cuprous iodide cluster luminescent materials.
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Plant residues are important sources of soil organic carbon in terrestrial ecosystems. The degradation of plant residue by microbes can influence the soil carbon cycle and sequestration. However, little is known about the microbial composition and function, as well as the accumulation of soil organic carbon (SOC) in response to the inputs of different quality plant residues in the desert environment. The present study evaluated the effects of plant residue addition from Pinus sylvestris var. mongolica (Pi), Artemisia desertorum (Ar) and Amorpha fruticosa (Am) on desert soil microbial community composition and function in a field experiment in the Mu Us Desert. The results showed that the addition of the three plant residues with different C/N ratios induced significant variation in soil microbial communities. The Am treatment (low C/N ratio) improved microbial diversity compared with the Ar and Pi treatments (medium and high C/N ratios). The variations in the taxonomic and functional compositions of the dominant phyla Actinobacteria and Proteobacteria were higher than those of the other phyla among the different treatments. Moreover, the network links between Proteobacteria and other phyla and the CAZyme genes abundances from Proteobacteria increased with increasing residue C/N, whereas those decreased for Actinobacteria. The SOC content of the Am, Ar and Pi treatments increased by 45.73%, 66.54% and 107.99%, respectively, as compared to the original soil. The net SOC accumulation was positively correlated with Proteobacteria abundance and negatively correlated with Actinobacteria abundance. These findings showed that changing the initial quality of plant residue from low C/N to high C/N can result in shifts in taxonomic and functional composition from Actinobacteria to Proteobacteria, which favors SOC accumulation. This study elucidates the ecophysiological roles of Actinobacteria and Proteobacteria in the desert carbon cycle, expands our understanding of the potential microbial-mediated mechanisms by which plant residue inputs affect SOC sequestration in desert soils, and provides valuable guidance for species selection in desert vegetation reconstruction.
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Clima Desértico , Microbiologia do Solo , Ecossistema , Carbono/análise , Carbono/metabolismo , Solo/química , Sequestro de Carbono , Microbiota , Bactérias/classificação , Bactérias/genéticaRESUMO
An electrolyte additive, with convenient operation and remarkable functions, has been regarded as an effective strategy for prolonging the cycle life of aqueous zinc ion batteries. However, it is still difficult to dynamically regulate the unstable Zn interface during long-term cycling. Herein, tricine was introduced as an efficient regulator to achieve a pH-stable and byproduct-free interface. The functional zwitterion of tricine not only inhibits interfacial pH perturbation and parasitic reactions by the trapping effect of an anionic group (-COO-) but also simultaneously creates a uniform electric field by the electrostatic shielding effect of a cationic group (-NH2+). Such synergy accordingly eliminates dendrite formation and creates a chemical equilibrium in the electrolyte, endowing the Zn||Zn cell with long-term Zn plating/stripping for 2060 h at 5 mA cm-2 and 720 h at 10 mA cm-2. As a result, the Zn||VS2 full cell under a high cathodic loading mass (8.6 mg cm-2) exhibits exceptional capacity retention of 93% after 1000 cycles.
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Ferroptosis, a unique form of programmed cell death trigged by lipid peroxidation and iron accumulation, has been implicated in embryonic erythropoiesis and aging. Our previous research demonstrated that lysophosphatidic acid receptor 3 (LPA3) activation mitigated oxidative stress in progeria cells and accelerated the recovery of acute anemia in mice. Given that both processes involve iron metabolism, we hypothesized that LPA3 activation might mediate cellular ferroptosis. In this study, we used an LPA3 agonist, 1-Oleoyl-2-O-methyl-rac-glycerophosphothionate (OMPT), to activate LPA3 and examine its effects on the ferroptosis process. OMPT treatment elevated anti-ferroptosis gene protein expression, including solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), heme oxygenase-1 (HO-1), and ferritin heavy chain (FTH1), in erastin-induced cells. Furthermore, OMPT reduced lipid peroxidation and intracellular ferrous iron accumulation, as evidenced by C11 BODIPY™ 581/591 Lipid Peroxidation Sensor and FerroOrange staining. These observations were validated by applying LPAR3 siRNA in the experiments mentioned above. In addition, the protein expression level of nuclear factor erythroid 2-related factor (NRF2), a key regulator of oxidative stress, was also enhanced in OMPT-treated cells. Lastly, we verified that LPA3 plays a critical role in erastin-induced ferroptotic human erythroleukemia K562 cells. OMPT rescued the erythropoiesis defect caused by erastin in K562 cells based on a Gly A promoter luciferase assay. Taken together, our findings suggest that LPA3 activation inhibits cell ferroptosis by suppressing lipid oxidation and iron accumulation, indicating that ferroptosis could potentially serve as a link among LPA3, erythropoiesis, and aging.
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Ferroptose , Receptores de Ácidos Lisofosfatídicos , Camundongos , Animais , Humanos , Receptores de Ácidos Lisofosfatídicos/genética , Receptores de Ácidos Lisofosfatídicos/metabolismo , Apoptose , Estresse Oxidativo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Ferro/metabolismoRESUMO
Effective elimination of heavy metals from complex wastewater is of great significance for industrial wastewater treatment. Herein, bimetallic adsorbent Fe3O4-CeO2 was prepared, and H2O2 was added to enhance Sb(V) adsorption by Fe3O4-CeO2 in complex wastewater of Sb(V) and aniline aerofloat (AAF) for the first time. Fe3O4-CeO2 showed good adsorption performance and could be rapidly separated by external magnetic field. After five adsorption/desorption cycles, Fe3O4-CeO2 still maintained good stability. The maximum adsorption capacities of Fe3O4-CeO2 in single Sb(V), AAF + Sb(V), and H2O2+AAF + Sb(V) systems were 77.33, 70.14, and 80.59 mg/g, respectively. Coexisting AAF inhibited Sb(V) adsorption. Conversely, additional H2O2 promoted Sb(V) removal in AAF + Sb(V) binary system, and made the adsorption capacity of Fe3O4-CeO2 increase by 14.90%. H2O2 could not only accelerate the reaction rate, but also reduce the optimal amount of adsorbent from 2.0 g/L to 1.2 g/L. Meanwhile, coexisting anions had little effect on Sb(V) removal by Fe3O4-CeO2+H2O2 process. The adsorption behaviors of Sb(V) in three systems were better depicted by pseudo-second-order kinetics, implying that the chemisorption was dominant. The complexation of AAF with Sb(V) hindered the adsorption of Sb(V) by Fe3O4-CeO2. The complex Sb(V) was oxidized and decomposed into free state by hydroxyl radicals produced in Fe3O4-CeO2+H2O2 process. Then the free Sb(V) was adsorbed by Fe3O4-CeO2 mostly through outer-sphere complexation. This work provides a new tactic for the treatment of heavy metal-organics complex wastewater.
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Peróxido de Hidrogênio , Águas Residuárias , Águas Residuárias/química , Peróxido de Hidrogênio/química , Adsorção , Poluentes Químicos da Água/química , Compostos de Anilina/química , Cério/químicaRESUMO
The aqueous zinc-ion battery is promising as grid scale energy storage device, but hindered by the instable electrode/electrolyte interface. Herein, we report the lean-water ionic liquid electrolyte for aqueous zinc metal batteries. The lean-water ionic liquid electrolyte creates the hydrophobic tri-layer interface assembled by first two layers of hydrophobic OTF- and EMIM+ and third layer of loosely attached water, beyond the classical Gouy-Chapman-Stern theory based electrochemical double layer. By taking advantage of the hydrophobic tri-layer interface, the lean-water ionic liquid electrolyte enables a wide electrochemical working window (2.93â V) with relatively high zinc ion conductivity (17.3â mS/cm). Furthermore, the anion crowding interface facilitates the OTF- decomposition chemistry to create the mechanically graded solid electrolyte interface layer to simultaneously suppress the dendrite formation and maintain the mechanical stability. In this way, the lean-water based ionic liquid electrolyte realizes the ultralong cyclability of over 10000 cycles at 20â A/g and at practical condition of N/P ratio of 1.5, the cumulated areal capacity reach 1.8â Ah/cm2 , which outperforms the state-of-the-art zinc metal battery performance. Our work highlights the importance of the stable electrode/electrolyte interface stability, which would be practical for building high energy grid scale zinc-ion battery.
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Utilizing the periodicity of the rotating machinery, dynamic clearance measurement can be achieved with a single swept light source without any additional auxiliary devices, which has the advantages of simplicity and reliability. However, there is a shortcoming that previous algorithm is not fast enough to achieve real-time measurement when the machinery rotates at high speed. Aiming at this shortcoming, utilizing the correlation between mimic signal and measurement signal, combined with information for multiple periods, the fast algorithms and dynamic clearance corrected model were proposed. And the relationship between demodulation speed and cycle numbers was also discussed. Simulation was carried out to discuss the influence of different algorithm on the demodulation speed and accuracy. A test system was set up in the simulated environment for clearance measurement, and the results show that, the demodulation time of the proposed algorithm costs decreased dramatically, the speed has increased by about ten times, and the dynamic clearance measurement error is less than 2 µm.
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OBJECTIVE: The aim of this study was to identify prognostic autophagy-related genes and lncRNAs to predict clinical outcomes in head and neck squamous cell carcinoma (HNSCC). SUBJECTS AND METHODS: Differentially expressed autophagy-related genes and autophagy-related lncRNAs were identified by comparing pare-carcinoma and carcinoma samples of HNSCC. And then, we constructed an ARG and an AR-lncRNA signature risk score. Receiver operating characteristic (ROC) curve analyses were performed to assess the prognostic prediction capacity. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) functional annotation were used to analysis the functions of ARGs and AR-lncRNAs. RESULTS: Six ARGs and thirteen AR-lncRNAs were identified in the ARG and AR-lncRNA signatures, and overall survival (OS) in the high-risk group was significantly shorter than the low-risk group. ROC analysis showed the ARG and AR-lncRNA signatures have excellent ability of predicting the total OS of patients with HNSCC. What's more, GSEA and GO functional annotation proved that autophagy-related pathways are mainly enriched in the high-risk group. CONCLUSIONS: These findings indicated that our ARG signature and AR-lncRNA signature could be considered to predict the prognosis of patients with HNSCC and provide a deep understanding of the biological mechanisms of autophagy in HNSCC.
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Neoplasias de Cabeça e Pescoço , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Regulação Neoplásica da Expressão Gênica , Prognóstico , Neoplasias de Cabeça e Pescoço/genética , Autofagia/genéticaRESUMO
Wireless sensor networks (WSNs) are widely used in various fields such as military, industrial, and transportation for real-time monitoring, sensing, and data collection of different environments or objects. However, the development of WSNs is hindered by several limitations, including energy, storage space, computing power, and data transmission rate. Among these, the availability of power energy plays a crucial role as it directly determines the lifespan of WSN. To extend the life cycle of WSN, two key approaches are power supply improvement and energy conservation. Therefore, we propose an energy harvesting system and a low-energy-consumption mechanism for WSNs. Firstly, we delved into the energy harvesting technology of WSNs, explored the utilization of solar energy and mechanical vibration energy to ensure a continuous and dependable power supply to the sensor nodes, and analyzed the voltage output characteristics of bistable piezoelectric cantilever. Secondly, we proposed a neighbor discovery mechanism that utilizes a separation beacon, is based on reply to ACK, and can facilitate the identification of neighboring nodes. This mechanism operates at a certain duty cycle ratio, significantly reduces idle listening time and results in substantial energy savings. In comparison to the Disco and U-connect protocols, our proposed mechanism achieved a remarkable reduction of 66.67% and 75% in the worst discovery delay, respectively. Furthermore, we introduced a data fusion mechanism based on integer wavelet transform. This mechanism effectively eliminates data redundancy caused by spatiotemporal correlation, resulting in a data compression rate of 5.42. Additionally, it significantly reduces energy consumption associated with data transmission by the nodes.
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BACKGROUND: Although a few meta-analyses were conducted to compare the risk of incident atrial fibrillation (AF) between sodium-glucose cotransporter-2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and other anti-hyperglycemic agents using indirect or direct comparison, the above analyses showed conflicting results with each other. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i, GLP-1RA, and dipeptidyl peptidase-4 inhibitor (DPP4i) among a large longitudinal cohort of diabetic patients. METHODS: In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, a total of 344,893, 44,370, and 393,100 consecutive patients with type 2 diabetes without preexisting AF receiving GLP-1RA, SGLT2i, and DPP4i, respectively, were enrolled from May 1, 2016, to December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates across paired study groups. Patients were followed from the drug index date until the occurrence of AF, death, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. RESULTS: After PSM, there were 245,442, 43,682, and 39,190 paired cohorts of SGLT2i-DPP4i, SGLT2i-GLP-1RA, and GLP-1RA-DPP4i, respectively. SGLT2i treatment was associated with lower risk of new-onset AF in participants with type 2 diabetes compared with either DPP4i [hazard ratio (HR):0.90; 95% confidential interval (CI) 0.84-0.96; P = 0.0028] or GLP-1RA [HR 0.74; 95% CI 0.63-0.88; P = 0.0007] treatment after PSM. There was no difference in the risk of incident AF between GLP-1RA and DPP4i users [HR 1.01; 95% CI 0.86-1.19; P = 0.8980]. The above findings persisted among several important subgroups. Dapagliflozin was specifically associated with a lower risk of new-onset AF compared with DPP4i (P interaction = 0.02). CONCLUSIONS: Compared with DPP4i, SGLT2i but not GLP-1RA was associated with a lower risk of incident AF in patients with type 2 diabetes.
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Fibrilação Atrial , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Dipeptidil Peptidases e Tripeptidil Peptidases/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemiantes/efeitos adversos , Estudos Retrospectivos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversosRESUMO
Revealing the ecological roles of core microbiota in the maintenance of the functional stability of soil microbiomes is crucial for sustainable ecosystem functioning; however, there is a dearth of whole-soil profile studies on the fundamental topic in microbial ecology, especially in the context of ecological restoration. Here, we explored whether core microbiota influence the temporal changes in the functional stability of soil microbiomes throughout the soil profile (i.e., soil depths of 0-300 cm) during natural succession in restored ex-arable ecosystems, via high-throughput amplicon and metagenomic sequencing. We revealed that core microbiota were essential for the maintenance of the functional stability of soil microbiomes in reforestation ecosystems. Specifically, the core taxa within one cluster of soil network, which had similar ecological preferences, had major contributions to functional stability. Reforestation significantly decreased the functional stability of soil microbiomes, which exhibited significant variations along the vertical soil profile in the reforested soils. Overall, the findings enhance our understanding of the factors driving functional stability in soil microbiomes, and suggests that core microbiota should be considered a key factor and integrated in policy and management activities targeting the enhancement and maintenance of functional stability and ecosystem sustainability in ecological restoration programs.
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Microbiota , Solo , Metagenômica , Microbiologia do SoloRESUMO
The interface between electron-donating (D) and electron-accepting (A) materials in organic photovoltaic (OPV) devices is commonly probed by charge-transfer (CT) electroluminescence (EL) measurements to estimate the CT energy, which critically relates to device open-circuit voltage. It is generally assumed that during CT-EL injected charges recombine at close-to-equilibrium energies in their respective density of states (DOS). Here, we explicitly quantify that CT-EL instead originates from higher-energy DOS site distributions significantly above DOS equilibrium energies. To demonstrate this, we have developed a quantitative and experimentally calibrated model for CT-EL at organic D/A heterointerfaces, which simultaneously accounts for the charge transport physics in an energetically disordered DOS and the Franck-Condon broadening. The 0-0 CT-EL transition lineshape is numerically calculated using measured energetic disorder values as input to 3-dimensional kinetic Monte Carlo simulations. We account for vibrational CT-EL overtones by selectively measuring the dominant vibrational phonon-mode energy governing CT luminescence at the D/A interface using fluorescence line-narrowing spectroscopy. Our model numerically reproduces the measured CT-EL spectra and their bias dependence and reveals the higher-lying manifold of DOS sites responsible for CT-EL. Lowest-energy CT states are situated â¼180 to 570 meV below the 0-0 CT-EL transition, enabling photogenerated carrier thermalization to these low-lying DOS sites when the OPV device is operated as a solar cell rather than as a light-emitting diode. Nonequilibrium site distribution rationalizes the experimentally observed weak current-density dependence of CT-EL and poses fundamental questions on reciprocity relations relating light emission to photovoltaic action and regarding minimal attainable photovoltaic energy conversion losses in OPV devices.
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BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in females of reproductive age, with a prevalence of 20%-33% in the general population. Interleukin (IL)-34 is a recently explored proinflammatory cytokine and is an important modulator in different disease types. However, the function of IL-34 in PCOS has yet to be investigated. OBJECTIVE: The purpose of this study was to determine the IL-34 serum level in women with PCOS and to compare it to that of a relatively healthy control group. Focusing on its relationship with IL-6, TNF-α, and IL-1ß and homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, and low-density lipoprotein cholesterol (LDL-C). MATERIALS AND METHODS: In this study, blood samples were obtained from 100 women with PCOS and 100 healthy control women for the purpose of estimating their serum levels of IL-34, IL-6, TNF-α, and IL-1ß using the enzyme-linked immunosorbent assay technique. RESULTS: Serum levels of IL-34, IL-6, TNF-α, and IL-1ß were all higher in PCOS women than in healthy controls, and the difference was highly statistically significant. Serum IL-34 concentration was positively correlated with IL-6, TNF-α, and IL-1ß concentration. Additionally, serum concentrations of IL-34 were positively correlated with HOMA-IR, triglyceride, and LDL-C. CONCLUSION: When compared to normal women, IL-34, IL-6, TNF-α, and IL-1ß levels were highly statistically significant in PCOS, and these high levels were associated with other cytokines (IL-6, TNF-α, and IL-1ß), HOMA-IR, triglyceride, and LDL-C.