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1.
Orphanet J Rare Dis ; 19(1): 183, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698482

RESUMO

BACKGROUND: With over 7000 Mendelian disorders, identifying children with a specific rare genetic disorder diagnosis through structured electronic medical record data is challenging given incompleteness of records, inaccurate medical diagnosis coding, as well as heterogeneity in clinical symptoms and procedures for specific disorders. We sought to develop a digital phenotyping algorithm (PheIndex) using electronic medical records to identify children aged 0-3 diagnosed with genetic disorders or who present with illness with an increased risk for genetic disorders. RESULTS: Through expert opinion, we established 13 criteria for the algorithm and derived a score and a classification. The performance of each criterion and the classification were validated by chart review. PheIndex identified 1,088 children out of 93,154 live births who may be at an increased risk for genetic disorders. Chart review demonstrated that the algorithm achieved 90% sensitivity, 97% specificity, and 94% accuracy. CONCLUSIONS: The PheIndex algorithm can help identify when a rare genetic disorder may be present, alerting providers to consider ordering a diagnostic genetic test and/or referring a patient to a medical geneticist.


Assuntos
Algoritmos , Doenças Raras , Humanos , Doenças Raras/genética , Doenças Raras/diagnóstico , Lactente , Recém-Nascido , Pré-Escolar , Feminino , Masculino , Registros Eletrônicos de Saúde , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Fenótipo
2.
Small ; : e2401299, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38746996

RESUMO

The immunosuppressive tumor microenvironment (TME) reduces the chimeric antigen receptor (CAR) T-cell therapy against solid tumors. Here, a CAR T cell membrane-camouflaged nanocatalyst (ACSP@TCM) is prepared to augment CAR T cell therapy efficacy against solid tumors. ACSP@TCM is prepared by encapsulating core/shell Au/Cu2- xSe and 3-bromopyruvate with a CAR T cell membrane. It is demonstrated that the CAR T cell membrane camouflaging has much better-targeting effect than the homologous tumors cell membrane camouflaging. ACSP@TCM has an appealing synergistic chemodynamic/photothermal therapy (CDT/PTT) effect that can induce the immunogenic cell death (ICD) of NALM 6 cells. Moreover, 3-bromopyruvate can inhibit the efflux of lactic acid by inhibiting the glycolysis process, regulating the acidity of TME, and providing a more favorable environment for the survival of CAR T cells. In addition, the photoacoustic (PA) imaging and computed tomography (CT) imaging performance can guide the ACSP@TCM-mediated tumor therapy. The results demonstrated that the ACSP@TCM significantly enhanced the CAR T cell therapy efficacy against NALM 6 solid tumor mass, and completely eliminated tumors. This work provides an effective tumor strategy for CAR T cell therapy in solid tumors.

3.
Physiol Plant ; 176(3): e14323, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38695188

RESUMO

Tomatoes are frequently challenged by various pathogens, among which Phytophthora capsici (P. capsici) is a destructive soil-borne pathogen that seriously threatens the safe production of tomatoes. Plant growth-promoting rhizobacteria (PGPR) positively induced plant resistance against multiple pathogens. However, little is known about the role and regulatory mechanism of PGPR in tomato resistance to P. capsici. Here, we identified a new strain Serratia plymuthica (S. plymuthica), HK9-3, which has a significant antibacterial effect on P. capsici infection. Meanwhile, stable colonization in roots by HK9-3, even under P. capsici infection, improved tomato growth parameters, root system architecture, photosynthetic capacity, and boosted biomass. Importantly, HK9-3 colonization significantly alleviated the damage caused by P. capsici infection through enhancing ROS scavenger ability and inducing antioxidant defense system and pathogenesis-related (PR) proteins in leaves, as evidenced by elevating the activities of peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and chitinase, ß-1,3-glucanase, and increasing the transcripts of POD, SOD, CAT, APX1, PAL1, PAL2, PAL5, PPO2, CHI17 and ß-1,3-glucanase genes. Notably, HK9-3 colonization not only effectively improved soil microecology and soil fertility, but also significantly enhanced fruit yield by 44.6% and improved quality. Our study presents HK9-3 as a promising and effective solution for controlling P. capsici infection in tomato cultivation while simultaneously promoting plant growth and increasing yield, which may have implications for P. capsici control in vegetable production.


Assuntos
Resistência à Doença , Phytophthora , Doenças das Plantas , Rizosfera , Serratia , Solanum lycopersicum , Solanum lycopersicum/microbiologia , Solanum lycopersicum/fisiologia , Solanum lycopersicum/genética , Phytophthora/fisiologia , Serratia/fisiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Antioxidantes/metabolismo , Raízes de Plantas/microbiologia , Raízes de Plantas/fisiologia
4.
Adv Mater ; : e2310480, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669281

RESUMO

Conjugated polymers are promising materials for thermoelectric applications, however, at present few effective and well-understood strategies exist to further advance their thermoelectric performance. Here a new model system is reported for a better understanding of the key factors governing their thermoelectric properties: aligned, ribbon-phase poly[2,5-bis(3-dodecylthiophen-2-yl)thieno[3,2-b]thiophene] (PBTTT) doped by ion-exchange doping. Using a range of microstructural and spectroscopic methods, the effect of controlled incorporation of tie-chains between the crystalline domains is studied through blending of high and low molecular weight chains. The tie chains provide efficient transport pathways between crystalline domains and lead to significantly enhanced electrical conductivity of 4810 S cm-1, which is not accompanied by a reduction in Seebeck coefficient or a large increase in thermal conductivity. Respectable power factors of 173 µW m-1 K-2 are demonstrated in this model system. The approach is generally applicable to a wide range of semicrystalline conjugated polymers and could provide an effective pathway for further enhancing their thermoelectric properties and overcome traditional trade-offs in optimization of thermoelectric performance.

5.
Cell Biosci ; 14(1): 43, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561835

RESUMO

The prevalence of Crohn's disease (CD), a subtype of inflammatory bowel disease (IBD), is increasing worldwide. The pathogenesis of CD is hypothesized to be related to environmental, genetic, immunological, and bacterial factors. Current studies have indicated that intestinal epithelial cells, including columnar, Paneth, M, tuft, and goblet cells dysfunctions, are strongly associated with these pathogenic factors. In particular, goblet cells dysfunctions have been shown to be related to CD pathogenesis by direct or indirect ways, according to the emerging studies. The mucus barrier was established with the help of mucins secreted by goblet cells. Not only do the mucins mediate the mucus barrier permeability and bacterium selection, but also, they are closely linked with the endothelial reticulum stress during the synthesis process. Goblet cells also play a vital role in immune response. It was indicated that goblet cells take part in the antigen presentation and cytokines secretion process. Disrupted goblet cells related immune process were widely discovered in CD patients. Meanwhile, dysbiosis of commensal and pathogenic microbiota can induce myriad immune responses through mucus and goblet cell-associated antigen passage. Microbiome dysbiosis lead to inflammatory reaction against pathogenic bacteria and abnormal tolerogenic response. All these three pathways, including the loss of mucus barrier function, abnormal immune reaction, and microbiome dysbiosis, may have independent or cooperative effect on the CD pathogenesis. However, many of the specific mechanisms underlying these pathways remain unclear. Based on the current understandings of goblet cell's role in CD pathogenesis, substances including butyrate, PPARγagonist, Farnesoid X receptor agonist, nuclear factor-Kappa B, nitrate, cytokines mediators, dietary and nutrient therapies were all found to have potential therapeutic effects on CD by regulating the goblet cells mediated pathways. Several monoclonal antibodies already in use for the treatment of CD in the clinical settings were also found to have some goblet cells related therapeutic targets. In this review, we introduce the disease-related functions of goblet cells, their relationship with CD, their possible mechanisms, and current CD treatments targeting goblet cells.

6.
J Am Chem Soc ; 146(17): 12087-12099, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38647488

RESUMO

Electron transfer during solid-liquid contact electrification has been demonstrated to produce reactive oxygen species (ROS) such as hydroxyl radicals (•OH) and superoxide anion radicals (•O2-). Here, we show that such a process also occurs in liquid-liquid contact electrification. By preparing perfluorocarbon nanoemulsions to construct a perfluorocarbon-water "liquid-liquid" interface, we confirmed that electrons were transferred from water to perfluorocarbon in ultrasonication-induced high-frequency liquid-liquid contact to produce •OH and •O2-. The produced ROS could be applied to ablate tumors by triggering large-scale immunogenic cell death in tumor cells, promoting dendritic cell maturation and macrophage polarization, ultimately activating T cell-mediated antitumor immune response. Importantly, the raw material for producing •OH is water, so the tumor therapy is not limited by the endogenous substances (O2, H2O2, etc.) in the tumor microenvironment. This work provides new perspectives for elucidating the mechanism of generation of free radicals in liquid-liquid contact and provides an excellent tumor therapeutic modality.


Assuntos
Fluorocarbonos , Água , Fluorocarbonos/química , Água/química , Camundongos , Animais , Neoplasias/tratamento farmacológico , Radicais Livres/química , Humanos , Radical Hidroxila/química , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacologia
7.
Cell Res ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605178

RESUMO

The suprachiasmatic nucleus (SCN) is the mammalian central circadian pacemaker with heterogeneous neurons acting in concert while each neuron harbors a self-sustained molecular clockwork. Nevertheless, how system-level SCN signals encode time of the day remains enigmatic. Here we show that population-level Ca2+ signals predict hourly time, via a group decision-making mechanism coupled with a spatially modular time feature representation in the SCN. Specifically, we developed a high-speed dual-view two-photon microscope for volumetric Ca2+ imaging of up to 9000 GABAergic neurons in adult SCN slices, and leveraged machine learning methods to capture emergent properties from multiscale Ca2+ signals as a whole. We achieved hourly time prediction by polling random cohorts of SCN neurons, reaching 99.0% accuracy at a cohort size of 900. Further, we revealed that functional neuron subtypes identified by contrastive learning tend to aggregate separately in the SCN space, giving rise to bilaterally symmetrical ripple-like modular patterns. Individual modules represent distinctive time features, such that a module-specifically learned time predictor can also accurately decode hourly time from random polling of the same module. These findings open a new paradigm in deciphering the design principle of the biological clock at the system level.

8.
Adv Mater ; : e2314062, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558210

RESUMO

Doping is a crucial strategy to enhance the performance of various organic electronic devices. However, in many cases, the random distribution of dopants in conjugated polymers leads to the disruption of the polymer microstructure, severely constraining the achievable performance of electronic devices. Here, it is shown that by ion-exchange doping polythiophene-based P[(3HT)1-x-stat-(T)x] (x = 0 (P1), 0.12 (P2), 0.24 (P3), and 0.36 (P4)), remarkably high electrical conductivity of >400 S cm-1 and power factor of >16 µW m-1 K-2 are achieved for the random copolymer P3, ranking it among highest ever reported for unaligned P3HT-based films, significantly higher than that of P1 (<40 S cm-1, <4 µW m-1 K-2). Although both polymers exhibit comparable field-effect transistor hole mobilities of ≈0.1 cm2 V-1 s-1 in the pristine state, after doping, Hall effect measurements indicate that P3 exhibits a large Hall mobility up to 1.2 cm2 V-1 s-1, significantly outperforming that of P1 (0.06 cm2 V-1 s-1). GIWAXS measurement determines that the in-plane π-π stacking distance of doped P3 is 3.44 Å, distinctly shorter than that of doped P1 (3.68 Å). These findings contribute to resolving the long-standing dopant-induced-disorder issues in P3HT and serve as an example for achieving fast charge transport in highly doped polymers for efficient electronics.

9.
Nanotechnology ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688249

RESUMO

Dealing with bone defects is a significant challenge to global health. Electrospinning in bone tissue engineering has emerged as a solution to this problem. In this study, we designed a PVDF-b-PTFE block copolymer by incorporating TFE, which induced a phase shift in PVDF from α to ß, thereby enhancing the piezoelectric effect. Utilizing the electrospinning process, we not only converted the material into a film with a significant surface area and high porosity but also intensified the piezoelectric effect. Then we used polydopamine (PDA) to immobilize BMP-2 onto PVDF-b-PTFE electrospun nanofibrous membranes, achieving a controlled release of BMP-2. The scaffold's characters were examined using SEM and XRD. To assess its osteogenic effects in vitro, we monitored the proliferation of MC3T3-E1 cells on the fibers, conducted ARS staining, and measured the expression of osteogenic genes. In vivo, bone regeneration effects were analyzed through micro-CT scanning and HE staining. ELISA assays confirmed that the sustained release of BMP-2 can be maintained for at least 28 days. SEM images and CCK-8 results demonstrated enhanced cell viability and improved adhesion in the experimental group. Furthermore, the experimental group exhibited more calcium nodules and higher expression levels of osteogenic genes, including COL-I, OCN, and RUNX2. HE staining and micro-CT scans revealed enhanced bone tissue regeneration in the defective area of the PDB group. Through extensive experimentation, we evaluated the scaffold's effectiveness in augmenting osteoblast proliferation and differentiation. This study emphasized the potential of piezoelectric PVDF-b-PTFE nanofibrous membranes with controlled BMP-2 release as a promising approach for bone tissue engineering, providing a viable solution for addressing bone defects.

10.
Nat Commun ; 15(1): 2471, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503787

RESUMO

The development of neuromorphic visual systems has recently gained momentum due to their potential in areas such as autonomous vehicles and robotics. However, current machine visual systems based on silicon technology usually contain photosensor arrays, format conversion, memory and processing modules. As a result, the redundant data shuttling between each unit, resulting in large latency and high-power consumption, seriously limits the performance of neuromorphic vision chips. Here, we demonstrate an artificial neural network (ANN) architecture based on an integrated 2D MoS2/Ag nanograting phototransistor array, which can simultaneously sense, pre-process and recognize optical images without latency. The pre-processing function of the device under photoelectric synergy ensures considerable improvement of efficiency and accuracy of subsequent image recognition. The comprehensive performance of the proof-of-concept device demonstrates great potential for machine vision applications in terms of large dynamic range (180 dB), high speed (500 ns) and low energy consumption per spike (2.4 × 10-17 J).

11.
Sci Rep ; 14(1): 6167, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486009

RESUMO

The management of surgical instruments is related to the safety and efficiency of surgical operations, and a surgical instruments information management system (SIIMS) has been developed. The aim of the current study is to explore the application value of the SIIMS in sports medicine specialty. A set of self-developed SIIMS for sports medicine surgeries was applied to the study. The application value of the SIIMS was verified by comparing the safety and efficiency of instrument manipulation before and after its application, with instrument accidents, instrument repair rate, instrument scrap rate and instrument use efficiency as indicators. Through the application of the SIIMS, the incidence of surgical instrument accidents decreased from 3.7 times to 1.8 times (P = 0.02), the number of instrument repair decreased from 7.7 times to 2.9 times (P = 0.00), and the number of scrapped instruments decreased from 5.1 to 2.3 (P = 0.03), when referred to per thousand operations. Before and after the application of the SIIMS, the average instrument use efficiency was 74.0% ± 3.3% and 88.2% ± 4.4%, respectively, with statistically significant difference (P = 0.00). The application of the SIIMS in sports medicine specialty is helpful to the fine management of surgical instruments, improve surgical safety and instrument use efficiency.


Assuntos
Gestão da Informação , Instrumentos Cirúrgicos
12.
Cell Mol Immunol ; 21(5): 510-526, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38472357

RESUMO

Acetaldehyde dehydrogenase 2 (ALDH2) mutations are commonly found in a subgroup of the Asian population. However, the role of ALDH2 in septic acute respiratory distress syndrome (ARDS) remains unknown. Here, we showed that human subjects carrying the ALDH2rs671 mutation were highly susceptible to developing septic ARDS. Intriguingly, ALDH2rs671-ARDS patients showed higher levels of blood cell-free DNA (cfDNA) and myeloperoxidase (MPO)-DNA than ALDH2WT-ARDS patients. To investigate the mechanisms underlying ALDH2 deficiency in the development of septic ARDS, we utilized Aldh2 gene knockout mice and Aldh2rs671 gene knock-in mice. In clinically relevant mouse sepsis models, Aldh2-/- mice and Aldh2rs671 mice exhibited pulmonary and circulating NETosis, a specific process that releases neutrophil extracellular traps (NETs) from neutrophils. Furthermore, we discovered that NETosis strongly promoted endothelial destruction, accelerated vascular leakage, and exacerbated septic ARDS. At the molecular level, ALDH2 increased K48-linked polyubiquitination and degradation of peptidylarginine deiminase 4 (PAD4) to inhibit NETosis, which was achieved by promoting PAD4 binding to the E3 ubiquitin ligase CHIP. Pharmacological administration of the ALDH2-specific activator Alda-1 substantially alleviated septic ARDS by inhibiting NETosis. Together, our data reveal a novel ALDH2-based protective mechanism against septic ARDS, and the activation of ALDH2 may be an effective treatment strategy for sepsis.


Assuntos
Aldeído-Desidrogenase Mitocondrial , Armadilhas Extracelulares , Camundongos Knockout , Neutrófilos , Síndrome do Desconforto Respiratório , Sepse , Animais , Sepse/complicações , Humanos , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/patologia , Camundongos , Armadilhas Extracelulares/metabolismo , Masculino , Modelos Animais de Doenças , Proteína-Arginina Desiminase do Tipo 4/metabolismo , Camundongos Endogâmicos C57BL , Ubiquitinação , Feminino , Peroxidase/metabolismo , Mutação
13.
bioRxiv ; 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38370804

RESUMO

Fluorescent biosensors revolutionized biomedical science by enabling the direct measurement of signaling activities in living cells, yet the current technology is limited in resolution and dimensionality. Here, we introduce highly sensitive chemigenetic kinase activity biosensors that combine the genetically encodable self-labeling protein tag HaloTag7 with bright far-red-emitting synthetic fluorophores. This technology enables five-color biosensor multiplexing, 4D activity imaging, and functional super-resolution imaging via stimulated emission depletion (STED) microscopy.

14.
Inorg Chem ; 63(9): 4364-4372, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38373009

RESUMO

For the most commonly applied platinum-based catalysts of direct methanol fuel cells, the adsorption ability toward reaction intermediates, including CO and OH, plays a vital role in their catalytic activity and antipoisoning in anodic methanol oxidation reaction (MOR). Herein, guided by a theoretical mechanism study, a favorable modulation of the electronic structure and intermediate adsorption energetics for Pt active sites is achieved by constructing the triple-phase interfacial structure between tin oxide (SnO2), platinum (Pt), and nitrogen-doped graphene (NG). From the strong electronic exchange at the triple-phase interface, the adsorption ability toward MOR reaction intermediates on Pt sites could be efficiently optimized, which not only inhibits the adsorption of CO* on active sites but also facilitates the adsorption of OH* to strip the poisoning species from the catalyst surface. Accordingly, the resulting catalyst delivers excellent catalytic activity and antipoisoning ability for MOR catalysis. The mass activity reaches 1098 mA mg-1Pt, 3.23 times of commercial Pt/C. Meanwhile, the initial potentials and main peak for CO oxidation are also located at a much lower potential (0.51 and 0.74 V) against commercial Pt/C (0.83 and 0.89 V).

15.
ACS Omega ; 9(7): 7471-7479, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38405499

RESUMO

Computational prediction of molecule-protein interactions has been key for developing new molecules to interact with a target protein for therapeutics development. Previous work includes two independent streams of approaches: (1) predicting protein-protein interactions (PPIs) between naturally occurring proteins and (2) predicting binding affinities between proteins and small-molecule ligands [also known as drug-target interaction (DTI)]. Studying the two problems in isolation has limited the ability of these computational models to generalize across the PPI and DTI tasks, both of which ultimately involve noncovalent interactions with a protein target. In this work, we developed Equivariant Graph of Graphs neural Network (EGGNet), a geometric deep learning (GDL) framework, for molecule-protein binding predictions that can handle three types of molecules for interacting with a target protein: (1) small molecules, (2) synthetic peptides, and (3) natural proteins. EGGNet leverages a graph of graphs (GoG) representation constructed from the molecular structures at atomic resolution and utilizes a multiresolution equivariant graph neural network to learn from such representations. In addition, EGGNet leverages the underlying biophysics and makes use of both atom- and residue-level interactions, which improve EGGNet's ability to rank candidate poses from blind docking. EGGNet achieves competitive performance on both a public protein-small-molecule binding affinity prediction task (80.2% top 1 success rate on CASF-2016) and a synthetic protein interface prediction task (88.4% area under the precision-recall curve). We envision that the proposed GDL framework can generalize to many other protein interaction prediction problems, such as binding site prediction and molecular docking, helping accelerate protein engineering and structure-based drug development.

16.
Front Microbiol ; 15: 1354936, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38380102

RESUMO

Rabies is a fatal zoonotic disease that poses a threat to public health. Rabies virus (RABV) is excreted in the saliva of infected animals, and is primarily transmitted by bite. The role of the salivary glands in virus propagation is significant, but has been less studied in the pathogenic mechanisms of RABV. To identify functionally important genes in the salivary glands, we used RNA sequencing (RNA-seq) to establish and analyze mRNA expression profiles in parotid tissue infected with two RABV strains, CVS-11 and PB4. The biological functions of differentially expressed genes (DEGs) were determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which revealed 3,764 DEGs (678 up-regulated and 3,086 down-regulated) in the CVS-11 infected group and 4,557 DEGs (874 up-regulated and 3,683 down-regulated) in the PB4 infected group. Various biological processes are involved, including the salivary secretion pathway and the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. This study provides the first mapping of the transcriptome changes in response to RABV infection in parotid tissue, offering new insights into the study of RABV-affected salivary gland function and RABV pathogenic mechanisms in parotid tissue. The salivary gland-enriched transcripts may be potential targets of interest for rabies disease control.

17.
Nat Metab ; 6(2): 273-289, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38286821

RESUMO

Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance and fatty liver disease. Here we show that high-fat diet (HFD) feeding causes mitochondrial fragmentation in inguinal white adipocytes from male mice, leading to reduced oxidative capacity by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes after HFD. Targeted deletion of RalA in white adipocytes prevents fragmentation of mitochondria and diminishes HFD-induced weight gain by increasing fatty acid oxidation. Mechanistically, RalA increases fission in adipocytes by reversing the inhibitory Ser637 phosphorylation of the fission protein Drp1, leading to more mitochondrial fragmentation. Adipose tissue expression of the human homolog of Drp1, DNM1L, is positively correlated with obesity and insulin resistance. Thus, chronic activation of RalA plays a key role in repressing energy expenditure in obese adipose tissue by shifting the balance of mitochondrial dynamics toward excessive fission, contributing to weight gain and metabolic dysfunction.


Assuntos
Resistência à Insulina , Masculino , Camundongos , Humanos , Animais , Adipócitos Brancos/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Aumento de Peso
18.
Small ; : e2310611, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212278

RESUMO

Rational tailoring of the electronic structure at the defined active center of reconstructed metal (oxy)hydroxides (MOOH) during oxygen evolution reaction (OER) remains a challenge. With the guidance of density functional theory (DFT), herein a dual-site regulatory strategy is reported to tailor the d-band center of the Co site in CoOOH via the controlled electronic transfer at the Ru─O─Co─O─Fe bonding structure. Through the bridged O2- site, electrons are vastly flowed from the t2g -orbital of the Ru site to the low-spin orbital of the Co site in the Ru-O-Co coordination and further transfer from the strong electron-electron repulsion of the Co site to the Fe site by the Co-O-Fe coordination, which balancing the electronic configuration of Co sites to weaken the over-strong adsorption energy barrier of OH* and O* , respectively. Benefiting from the highly active of the Co site, the constructed (Ru2 Fe2 Co6 )OOH provide an extremely low overpotential of 248 mV and a Tafel slope of 32.5 mV dec-1 at 10 mA cm-2 accompanied by long durability in alkaline OER, far superior over the pristine and Co-O-Fe bridged CoOOH catalysts. This work provides guidance for the rational design and in-depth analysis of the optimized role of metal dual-sites.

19.
BMC Psychiatry ; 24(1): 65, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263028

RESUMO

BACKGROUND: Delirium is prevalent in ischemic stroke patients, particularly those in the intensive care unit (ICU), and it poses a significant burden on patients and caregivers, leading to increased mortality rates, prolonged hospital stays, and impaired cognitive function. Dysphagia, a common symptom in critically ill patients with ischemic stroke, further complicates their condition. However, the association between dysphagia and delirium in this context remains unclear. The objective of this study was to investigate the correlation between dysphagia and delirium in ICU patients with ischemic stroke. METHODS: A retrospective analysis was conducted on adult patients diagnosed with ischemic stroke at a medical center in Boston. Ischemic stroke cases were identified using the ninth and tenth revisions of the International Classification of Diseases. Dysphagia was defined as a positive bedside swallowing screen performed by medical staff on the day of ICU admission, while delirium was assessed using the ICU Confusion Assessment Method and review of nursing notes. Logistic regression models were used to explore the association between dysphagia and delirium. Causal mediation analysis was employed to identify potential mediating variables. RESULTS: The study comprised 1838 participants, with a median age of approximately 70 years, and 50.5% were female. Among the total study population, the prevalence of delirium was 43.4%, with a higher prevalence observed in the dysphagia group (60.7% vs. 40.8%, p < 0.001) compared to the non-dysphagia group. After adjusting for confounding factors including age, sex, race, dementia, depression, sedative medications, history of falls, visual or hearing deficit, sequential organ failure score, and Glasgow coma score, multifactorial logistic regression analysis demonstrated a significant association between dysphagia and an increased likelihood of delirium (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.07-2.05; p = 0.018; E-value = 1.73). Causal mediation analysis revealed that serum albumin levels partially mediated the association between dysphagia and delirium in critically ill patients with ischemic stroke (average causal mediated effect [ACME]: 0.02, 95% CI: 0.01 to 0.03; p < 0.001). CONCLUSION: ICU admission dysphagia may independently contribute to the risk of delirium in patients with ischemic stroke. Early identification and intervention in ischemic stroke patients with dysphagia may help mitigate the risk of delirium and improve patient prognosis.


Assuntos
Transtornos de Deglutição , Delírio , AVC Isquêmico , Adulto , Humanos , Feminino , Idoso , Masculino , Estudos de Coortes , Estudos Retrospectivos , Estado Terminal , Unidades de Terapia Intensiva
20.
Sci Total Environ ; 915: 170029, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38244629

RESUMO

A novel S-scheme heterojunction photocatalyst carbon quantum dots (CQDs)/BiFeO3/BiOBr (CBB) was synthesized via a facile hydrothermal method, which was highly effective in activating peroxymonosulfate (PMS) to photodegrade imidacloprid (IMD) (one of the typical neonicotinoid insecticides (NEOs)) under visible light irradiation. Based on the physicochemical and photoelectrochemical analysis, the super photocatalytic performance of the CBB photocatalyst was contributed to the enhanced separation and transfer of photogenerated electrons (e-) and holes (h+), the activation of PMS by reactive species, and the wider light absorption range induced by CQDs. Moreover, the intermediate products and possible photodegradation pathways of IMD were confirmed through high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) detection and density functional theory (DFT) calculations. Although the photodegradation of IMD in the CBB/PMS/Vis system can be affected by the water quality parameters (i.e., acid group anions, pH, and the presence of humic acid (HA)), the synthesized CBB photocatalyst showed excellent photocatalytic performance in multiple natural water samples. This study provides a new idea to construct an effective and efficient heterojunction photocatalyst, which may have great advantages in photocatalytic degradation of NEOs and possibly other emerging contaminants in the aquatic environment.

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