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1.
Small ; : e2404437, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39268805

RESUMEN

The energy density of lithium-metal batteries (LMBs) relies substantially on the thickness of the lithium-metal anode. However, a bare, thin lithium foil electrode is vulnerable to fragmentation due to the inhomogeneity of the lithium stripping/plating process, disrupting the electron conduction pathway along the electrode. Accordingly, the current collector is an integral part to prevent the resulting loss of electronic conductivity. However, the common use of a heavy and lithiophobic Cu current collector results in a great anode mass increase and unsatisfactory lithium plating behavior, limiting both the achievable specific energy and the cycle life of LMBs. Herein, a metal-free polymer-based current collector is reported that allows for a substantial mass reduction, while simultaneously extending the cycle life of the lithium-metal anode. The specific mass of the ultra-light, 10 µm thick polymer-based current collector is only 1.03 mg cm-2, which is ≈11% of a 10 µm thick copper foil (8.96 mg cm-2). As a result, LMB cells employing this novel current collector provide a specific energy of 448 Wh kg-1, which is almost 18% higher than that of LMBs using the copper current collector (378 Wh kg-1), and a greatly enhanced cycle life owing to a more homogeneous lithium deposition.

2.
STAR Protoc ; 5(3): 103235, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39116197

RESUMEN

Selenoprotein thioredoxin reductase 1 (TXNRD1) is a promising therapeutic target, with several inhibitors reported to inhibit TXNRD1 activity. These inhibitors have the potential for applications such as anti-tumor medications. Here, we present a protocol for assessing irreversible inhibitors of TXNRD1. We describe four assays covering cellular TXNRD activity measurement, recombinant enzyme-based activity determination, differential scanning fluorimetry (DSF), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. This protocol will facilitate the screening and development of potential small-molecule inhibitors of TXNRD1.

3.
Biol Trace Elem Res ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39141196

RESUMEN

Mammalian cytosolic selenoprotein thioredoxin reductase (TXNRD1) is crucial for maintaining the reduced state of cellular thioredoxin 1 (TXN1) and is commonly up-regulated in cancer cells. TXNRD1 has been identified as an effective target in cancer chemotherapy. Discovering novel TXNRD1 inhibitors and elucidating the cellular effects of TXNRD1 inhibition are valuable for developing targeted therapies based on redox regulation strategies. In this study, we demonstrated that butein, a plant-derived small molecule flavonoid, is a novel TXNRD1 inhibitor. We found that butein irreversibly inhibited recombinant TXNRD1 activity in a time-dependent manner. Using TXNRD1 mutant variants and LC-MS, we identified that butein modifies the catalytic cysteine (Cys) residues of TXNRD1. In cellular contexts, butein promoted the accumulation of reactive oxygen species (ROS) and exhibited cytotoxic effects in HeLa cells. Notably, we found that pharmacological inhibition of TXNRD1 by butein overcame the cisplatin resistance of A549 cisplatin-resistant cells, accompanied by increased cellular ROS levels and enhanced expression of p53. Taken together, the results of this study demonstrate that butein is an effective small molecule inhibitor of TXNRD1, highlighting the therapeutic potential of inhibiting TXNRD1 in platinum-resistant cancer cells.

4.
Adv Sci (Weinh) ; 11(30): e2401123, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38864344

RESUMEN

Soft robots have the advantage of adaptability and flexibility in various scenarios and tasks due to their inherent flexibility and mouldability, which makes them highly promising for real-world applications. The development of electronic skin (E-skin) perception systems is crucial for the advancement of soft robots. However, achieving both exteroceptive and proprioceptive capabilities in E-skins, particularly in terms of decoupling and classifying sensing signals, remains a challenge. This study presents an E-skin with mixed electronic and ionic conductivity that can simultaneously achieve exteroceptive and proprioceptive, based on the resistance response of conductive hydrogels. It is integrated with soft robots to enable state perception, with the sensed signals further decoded using the machine learning model of decision trees and random forest algorithms. The results demonstrate that the newly developed hydrogel sensing system can accurately predict attitude changes in soft robots when subjected to varying degrees of pressing, hot pressing, bending, twisting, and stretching. These findings that multifunctional hydrogels combine with machine learning to decode signals may serve as a basis for improving the sensing capabilities of intelligent soft robots in future advancements.


Asunto(s)
Aprendizaje Automático , Robótica , Robótica/métodos , Hidrogeles , Humanos , Dispositivos Electrónicos Vestibles , Diseño de Equipo/métodos
5.
Nano Lett ; 24(17): 5332-5341, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38634554

RESUMEN

Alloying-type anode materials provide high capacity for lithium-ion batteries; however, they suffer pulverization problems resulting from the volume change during cycling. Realizing the cycling reversibility of these anodes is therefore critical for sustaining their electrochemical performance. Here, we investigate the structural reversibility of Sn NPs during cycling at atomic-level resolution utilizing in situ high-resolution TEM. We observed a surprisingly near-perfect structural reversibility after a complete cycle. A three-step phase transition happens during lithiation, accompanied by the generation of a significant number of defects, grain boundaries, and up to 202% volume expansion. In subsequent delithiation, the volume, morphology, and crystallinity of the Sn NPs were restored to their initial state. Theoretical calculations show that compressive stress drives the removal of vacancies generated within the NPs during delithiation, therefore maintaining their intact morphology. This work demonstrates that removing vacancies during cycling can efficiently improve the structural reversibility of high-capacity anode materials.

6.
Artif Intell Med ; 149: 102807, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38462276

RESUMEN

BACKGROUND: The breakdown of healthcare facilities is a huge challenge for hospitals. Medical images obtained by Computed Tomography (CT) provide information about the patients' physical conditions and play a critical role in diagnosis of disease. To deliver high-quality medical images on time, it is essential to minimize the occurrence frequencies of anomalies and failures of the equipment. METHODS: We extracted the real-time CT equipment status time series data such as oil temperature, of three equipment, between May 19, 2020, and May 19, 2021. Tube arcing is treated as the classification label. We propose a dictionary-based data-driven model SAX-HCBOP, where the two methods, Histogram-based Information Gain Binning (HIGB) and Coefficient improved Bag of Pattern (CoBOP), are implemented to transform the data into the bag-of-words paradigm. We compare our model to the existing predictive maintenance models based on statistical and time series classification algorithms. RESULTS: The results show that the Accuracy, Recall, Precision and F1-score of the proposed model achieve 0.904, 0.747, 0.417, 0.535, respectively. The oil temperature is identified as the most important feature. The proposed model is superior to other models in predicting CT equipment anomalies. In addition, experiments on the public dataset also demonstrate the effectiveness of the proposed model. CONCLUSIONS: The two proposed methods can improve the performance of the dictionary-based time series classification methods in predictive maintenance. In addition, based on the proposed real-time anomaly prediction system, the model assists hospitals in making accurate healthcare facilities maintenance decisions.


Asunto(s)
Algoritmos , Tomografía Computarizada por Rayos X , Humanos , Tomografía Computarizada por Rayos X/métodos , Hospitales , Atención a la Salud
7.
BMC Med ; 22(1): 59, 2024 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-38331807

RESUMEN

BACKGROUND: Adverse childhood experiences (ACEs), including childhood maltreatment, have been linked with increased risk of diabetes and obesity during adulthood. A comprehensive assessment on the associations between childhood maltreatment and all major endocrine diseases, as well as the relative importance of different proposed mechanistic pathways on these associations, is currently lacking. METHODS: Based on the UK Biobank, we constructed a cohort including 151,659 participants with self-reported data on childhood maltreatment who were 30 years of age or older on/after January 1, 1985. All participants were followed from the index date (i.e., January 1, 1985, or their 30th birthday, whichever came later) until the first diagnosis of any or specific (12 individual diagnoses and 9 subtypes) endocrine diseases, death, or the end of follow-up (December 31, 2019), whichever occurred first. We used Cox models to examine the association of childhood maltreatment, treated as continuous (i.e., the cumulative number of experienced childhood maltreatment), ordinal (i.e., 0, 1 and ≥ 2), or binary (< 2 and ≥ 2) variable, with any and specific endocrine diseases, adjusted for multiple covariates. We further examined the risk of having multiple endocrine diseases using Linear or Logistic Regression models. Then, sequential mediation analyses were performed to assess the contribution of four possible mechanisms (i.e., suboptimal socioeconomic status (SES), psychological adversities, unfavorable lifestyle, and biological alterations) on the observed associations. RESULTS: During an average follow-up of 30.8 years, 20,885 participants received a diagnosis of endocrine diseases. We observed an association between the cumulative number of experienced childhood maltreatment and increased risk of being diagnosed with any endocrine disease (adjusted hazard ratio (HR) = 1.10, 95% confidence interval 1.09-1.12). The HR was 1.26 (1.22-1.30) when comparing individuals ≥ 2 with those with < 2 experienced childhood maltreatment. We further noted the most pronounced associations for type 2 diabetes (1.40 (1.33-1.48)) and hypothalamic-pituitary-adrenal (HPA)-axis-related endocrine diseases (1.38 (1.17-1.62)), and the association was stronger for having multiple endocrine diseases, compared to having one (odds ratio (95% CI) = 1.24 (1.19-1.30), 1.35 (1.27-1.44), and 1.52 (1.52-1.53) for 1, 2, and ≥ 3, respectively). Sequential mediation analyses showed that the association between childhood maltreatment and endocrine diseases was consistently and most distinctly mediated by psychological adversities (15.38 ~ 44.97%), while unfavorable lifestyle (10.86 ~ 25.32%) was additionally noted for type 2 diabetes whereas suboptimal SES (14.42 ~ 39.33%) for HPA-axis-related endocrine diseases. CONCLUSIONS: Our study demonstrates that adverse psychological sequel of childhood maltreatment constitutes the main pathway to multiple endocrine diseases, particularly type 2 diabetes and HPA-axis-related endocrine diseases. Therefore, increased access to evidence-based mental health services may also be pivotal in reducing the risk of endocrine diseases among childhood maltreatment-exposed individuals.


Asunto(s)
Maltrato a los Niños , Diabetes Mellitus Tipo 2 , Enfermedades del Sistema Endocrino , Niño , Humanos , Adulto , Análisis de Mediación , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Maltrato a los Niños/psicología , Enfermedades del Sistema Endocrino/epidemiología , Enfermedades del Sistema Endocrino/etiología , Obesidad
8.
J Chin Med Assoc ; 87(4): 393-399, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38380911

RESUMEN

BACKGROUND: Vegetarian diets have been shown to lower the risks of hyperuricemia and gout. Little is known about the risk factors of hyperuricemia in vegetarians. METHODS: This community-based retrospective case-control study was conducted to establish prediction models for hyperuricemia. From September 5, 2005, to December 31, 2016, 7331 adult vegetarians were recruited at Taipei Tzu Chi Hospital. Hyperuricemia was defined as a serum uric acid concentration greater than 7 mg/dL. RESULTS: There were 593 (8.1%) vegetarians with hyperuricemia and 6738 (91.9%) without hyperuricemia. We stepwise built up three models for predicting hyperuricemia in vegetarians. The full model (model 3) has the highest area under the receiver operating characteristic curve (AUROC, 85.52%). Additionally, the AUROC of model 3 is 77.97% and 84.85% in vegetarians with or without prior gout history, respectively. Moreover, male gender, hyperlipidemia, body mass index, and serum albumin are independent risk factors for hyperuricemia in vegetarians. In contrast, estimated glomerular filtration rate and proteinuria are independently associated with lower risks of hyperuricemia in vegetarians. CONCLUSION: Our study revealed that risk factors for hyperuricemia, which includes clinical characteristics, account for more than 85% of discriminatory performance in Taiwanese vegetarians. This model may be helpful for monitoring and preventing hyperuricemia in the population.


Asunto(s)
Gota , Hiperuricemia , Adulto , Masculino , Humanos , Hiperuricemia/epidemiología , Hiperuricemia/etiología , Ácido Úrico , Estudios Retrospectivos , Estudios de Casos y Controles , Taiwán/epidemiología , Factores de Riesgo , Gota/epidemiología , Vegetarianos
9.
Redox Biol ; 70: 103050, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38277963

RESUMEN

Thioredoxin reductase (TXNRD) is a selenoprotein that plays a crucial role in cellular antioxidant defense. Previously, a distinctive guiding bar motif was identified in TXNRD1, which influences the transfer of electrons. In this study, utilizing single amino acid substitution and Excitation-Emission Matrix (EEM) fluorescence spectrum analysis, we discovered that the guiding bar communicates with the FAD and modulates the electron flow of the enzyme. Differential Scanning Fluorimetry (DSF) analysis demonstrated that the aromatic amino acid in guiding bar is a stabilizer for TXNRD1. Kinetic analysis revealed that the guiding bar is vital for the disulfide reductase activity but hinders the selenocysteine-independent reduction activity of TXNRD1. Meanwhile, the guiding bar shields the selenocysteine residue of TXNRD1 from the attack of electrophilic reagents. We also found that the inhibition of TXNRD1 by caveolin-1 scaffolding domain (CSD) peptides and compound LCS3 did not bind to the guiding bar motif. In summary, the obtained results highlight new aspects of the guiding bar that restrict the flexibility of the C-terminal redox motif and govern the transition from antioxidant to pro-oxidant.


Asunto(s)
Tiorredoxina Reductasa 1 , Antioxidantes/metabolismo , Cinética , Oxidación-Reducción , Selenocisteína/metabolismo , Tiorredoxina Reductasa 1/química , Tiorredoxina Reductasa 1/metabolismo , Reductasa de Tiorredoxina-Disulfuro/metabolismo , Humanos
10.
Molecules ; 28(19)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37836684

RESUMEN

Targeting thioredoxin reductase (TXNRD) with low-weight molecules is emerging as a high-efficacy anti-cancer strategy in chemotherapy. Sanguinarine has been reported to inhibit the activity of TXNRD1, indicating that benzophenanthridine alkaloid is a fascinating chemical entity in the field of TXNRD1 inhibitors. In this study, the inhibition of three benzophenanthridine alkaloids, including chelerythrine, sanguinarine, and nitidine, on recombinant TXNRD1 was investigated, and their anti-cancer mechanisms were revealed using three gastric cancer cell lines. Chelerythrine and sanguinarine are more potent inhibitors of TXNRD1 than nitidine, and the inhibitory effects take place in a dose- and time-dependent manner. Site-directed mutagenesis of TXNRD1 and in vitro inhibition analysis proved that chelerythrine or sanguinarine is primarily bound to the Sec498 residue of the enzyme, but the neighboring Cys497 and remaining N-terminal redox-active cysteines could also be modified after the conjugation of Sec498. With high similarity to sanguinarine, chelerythrine exhibited cytotoxic effects on multiple gastric cancer cell lines and suppressed the proliferation of tumor spheroids derived from NCI-N87 cells. Chelerythrine elevated cellular levels of reactive oxygen species (ROS) and induced endoplasmic reticulum (ER) stress. Moreover, the ROS induced by chelerythrine could be completely suppressed by the addition of N-acetyl-L-cysteine (NAC), and the same is true for sanguinarine. Notably, Nec-1, an RIPK1 inhibitor, rescued the chelerythrine-induced rapid cell death, indicating that chelerythrine triggers necroptosis in gastric cancer cells. Taken together, this study demonstrates that chelerythrine is a novel inhibitor of TXNRD1 by targeting Sec498 and possessing high anti-tumor properties on multiple gastric cancer cell lines by eliciting necroptosis.


Asunto(s)
Alcaloides , Antineoplásicos , Neoplasias Gástricas , Humanos , Benzofenantridinas/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Necroptosis , Alcaloides/farmacología , Alcaloides/química , Oxidación-Reducción
11.
BMC Med Inform Decis Mak ; 23(1): 166, 2023 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-37626352

RESUMEN

BACKGROUND: Large-scale medical equipment, which is extensively implemented in medical services, is of vital importance for diagnosis but vulnerable to various anomalies and failures. Most hospitals that conduct regular maintenance have been suffering from medical equipment-related incidents for years. Currently, the Internet of Medical Things (IoMT) has emerged as a crucial tool in monitoring the real-time status of the medical equipment. In this paper, we develop an IoMT system of Computed Tomography (CT) equipment in the West China Hospital, Sichuan University and collected the system status time-series data. Novel multivariate time-series classification models and frameworks are proposed to predict the anomalies of CT equipment. The important features that are closely related to the equipment anomalies are identified with the model. METHODS: We extracted the real-time CT equipment status time-series data of 11 equipment between May 19, 2020 and May 19, 2021 from the IoMT, which includes the equipment oil temperature, anode voltage, etc. The arcs are identified as labels of anomalies due to their relationship with decreased imaging quality and CT equipment failures. To improve prediction accuracy, the statistics and transformations of the raw historical time-series data segment in the sliding time window are used to construct new features. Due to the particularity of time-series data, two frameworks are proposed for splitting the training and test sets. Then the Decision Tree, Support Vector Machine, Logistic Regression, Naive Bayesian, and K-Nearest Neighbor classification models are used to classify the system status. We also compare our model to state-of-the-art models. RESULTS: The results show that the anomaly prediction accuracy and recall of our method are 79% and 77%, respectively. The oil temperature and anode voltage are identified as the decisive features that may lead to anomalies. The proposed model outperforms the others when predicting the anomalies of the CT equipment based on our dataset. CONCLUSIONS: The proposed method could predict the state of CT equipment and be used as a reference for practical maintenance, where unexpected anomalies of medical equipment could be reduced. It also brings new insights into how to handle non-uniform and imbalanced time series data in practical cases.


Asunto(s)
Tomografía Computarizada por Rayos X , Humanos , Teorema de Bayes , China , Análisis por Conglomerados , Electrodos
12.
J Cell Biol ; 222(11)2023 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-37624117

RESUMEN

Sexually dimorphic behaviors are ubiquitous throughout the animal kingdom. Although both sex-specific and sex-shared neurons have been functionally implicated in these diverse behaviors, less is known about the roles of sex-shared neurons. Here, we discovered sexually dimorphic cholinergic synaptic transmission in C. elegans occurring at neuromuscular junctions (NMJs), with males exhibiting increased release frequencies, which result in sexually dimorphic locomotion behaviors. Scanning electron microscopy revealed that males have significantly more synaptic vesicles (SVs) at their cholinergic synapses than hermaphrodites. Analysis of previously published transcriptome identified the male-enriched transcripts and focused our attention on UNC-43/CaMKII. We ultimately show that differential accumulation of UNC-43 at cholinergic neurons controls axonal SV abundance and synaptic transmission. Finally, we demonstrate that sex reversal of all neurons in hermaphrodites generates male-like cholinergic transmission and locomotion behaviors. Thus, beyond demonstrating UNC-43/CaMKII as an essential mediator of sex-specific synaptic transmission, our study provides molecular and cellular insights into how sex-shared neurons can generate sexually dimorphic locomotion behaviors.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Unión Neuromuscular , Transmisión Sináptica , Animales , Femenino , Masculino , Caenorhabditis elegans/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Neuronas , Proteínas de Caenorhabditis elegans/genética
13.
J Phys Chem Lett ; 14(29): 6647-6657, 2023 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-37462525

RESUMEN

This Perspective focuses on recent advances in understanding ultrafast processes involved in photoinduced structural phase transitions and proposes a strategy for precise manipulation of such transitions. It has been demonstrated that photoexcited carriers occupying empty antibonding or bonding states generate atomic driving forces that lead to either stretching or shortening of associated bonds, which in turn induce collective and coherent motions of atoms and yield structural transitions. For instance, phase transitions in IrTe2 and VO2, and nonthermal melting in Si, can be explained by the occupation of specific local bonding or antibonding states during laser excitation. These cases reveal the electronic-orbital-selective nature of laser-induced structural transitions. Based on this understanding, we propose an inverse design protocol for achieving or preventing a target structural transition by controlling the related electron occupations with orbital-selective photoexcitation. Overall, this Perspective provides a comprehensive overview of recent advancements in dynamical structural control in solid materials.

14.
Artículo en Inglés | MEDLINE | ID: mdl-37252872

RESUMEN

Most stroke survivors have mobility deficits and show a pathological gait pattern. Seeking to enhance the gait performance among this population, we have developed a hybrid cable-driven lower limb exoskeleton (called SEAExo). This study aimed to determine the effects of SEAExo with personalized assistance on immediate changes in gait performance of people after stroke. Gait metrics (i.e., the foot contact angle, knee flexion peak, temporal gait symmetry indices) and muscle activities were the primary outcomes to evaluate the assistive performance. Seven subacute stroke survivors participated and completed the experiment with three comparison sessions, i.e., walking without SEAExo (served as baseline) and without/with personalized assistance, at their preferred walking speeds. Compared to the baseline, we observed increases in the foot contact angle and knee flexion peak by 70.1% ( ) and 60.0% ( ) with personalized assistance. Personalized assistance contributed to the improvements in temporal gait symmetry of more impaired participants ( ), and it led to a 22.8% and 51.3% ( ) reduction in the muscle activities of ankle flexor muscles. These results demonstrate that SEAExo with personalized assistance has the potential to enhance post-stroke gait rehabilitation in real-world clinical settings.


Asunto(s)
Dispositivo Exoesqueleto , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Benchmarking , Fenómenos Biomecánicos , Marcha/fisiología , Tobillo , Caminata/fisiología
15.
Nutrients ; 15(6)2023 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-36986174

RESUMEN

Hyperuricemia is a well-known risk factor for chronic kidney disease (CKD). Little is known about whether a vegetarian diet is associated with a lower risk of CKD in patients with hyperuricemia. From 5 September 2005, to 31 December 2016, we retrospectively included clinically stable patients with hyperuricemia who received health check-ups at Taipei Tzu Chi Hospital. All participants completed a dietary habits questionnaire to determine whether they were omnivorous, lacto-ovo vegetarian, or vegan. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 or the presence of proteinuria. A total of 3618 patients with hyperuricemia were recruited for this cross-sectional study, consisting of 225 vegans, 509 lacto-ovo vegetarians, and 2884 omnivores. After adjusting for age and sex, vegans had a significantly lower odds ratio (OR) of CKD than omnivores (OR, 0.62; p = 0.006). The OR of CKD remained significantly lower in vegans after adjusting for additional confounders (OR, 0.69; p = 0.04). Additionally, age (per year OR, 1.06; p < 0.001), diabetes mellitus (OR, 2.12; p < 0.001), hypertension (OR, 1.73; p < 0.001), obesity (OR, 1.24; p = 0.02), smoking (OR, 2.05; p < 0.001), and very high uric acid levels (OR, 2.08; p < 0.001) were independent risk factors for CKD in patients with hyperuricemia. Moreover, structural equation modeling revealed that a vegan diet was associated with a lower OR of CKD (OR, 0.69; p < 0.05). A vegan diet is associated with a 31% lower risk of CKD in patients with hyperuricemia. A vegan diet may be beneficial in reducing the occurrence of CKD in patients with hyperuricemia.


Asunto(s)
Hiperuricemia , Insuficiencia Renal Crónica , Humanos , Dieta Vegana , Hiperuricemia/complicaciones , Hiperuricemia/epidemiología , Estudios Transversales , Estudios Retrospectivos , Dieta Vegetariana , Vegetarianos , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Dieta
16.
Structure ; 31(4): 424-434.e6, 2023 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-36863339

RESUMEN

Ca2+-dependent activator proteins for secretion (CAPSs) are required for Ca2+-regulated exocytosis in neurons and neuroendocrine cells. CAPSs contain a pleckstrin homology (PH) domain that binds PI(4,5)P2-membrane. There is also a C2 domain residing adjacent to the PH domain, but its function remains unclear. In this study, we solved the crystal structure of the CAPS-1 C2PH module. The structure showed that the C2 and PH tandem packs against one another mainly via hydrophobic residues. With this interaction, the C2PH module exhibited enhanced binding to PI(4,5)P2-membrane compared with the isolated PH domain. In addition, we identified a new PI(4,5)P2-binding site on the C2 domain. Disruption of either the tight interaction between the C2 and PH domains or the PI(4,5)P2-binding sites on both domains significantly impairs CAPS-1 function in Ca2+-regulated exocytosis at the Caenorhabditis elegans neuromuscular junction (NMJ). These results suggest that the C2 and PH domains constitute an effective unit to promote Ca2+-regulated exocytosis.


Asunto(s)
Proteínas de Unión al Calcio , Dominios Homólogos a Pleckstrina , Animales , Proteínas de Unión al Calcio/química , Exocitosis , Dominios Proteicos , Sitios de Unión , Caenorhabditis elegans/metabolismo
17.
Nat Commun ; 14(1): 1436, 2023 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-36918518

RESUMEN

Disturbed inhibitory synaptic transmission has functional impacts on neurodevelopmental and psychiatric disorders. An essential mechanism for modulating inhibitory synaptic transmission is alteration of the postsynaptic abundance of GABAARs, which are stabilized by postsynaptic scaffold proteins and recruited by presynaptic signals. However, how GABAergic neurons trigger signals to transsynaptically recruit GABAARs remains elusive. Here, we show that UNC-43/CaMKII functions at GABAergic neurons to recruit GABAARs and modulate inhibitory synaptic transmission at C. elegans neuromuscular junctions. We demonstrate that UNC-43 promotes presynaptic MADD-4B/Punctin secretion and NRX-1α/Neurexin surface delivery. Together, MADD-4B and NRX-1α recruit postsynaptic NLG-1/Neuroligin and stabilize GABAARs. Further, the excitation of GABAergic neurons potentiates the recruitment of NLG-1-stabilized-GABAARs, which depends on UNC-43, MADD-4B, and NRX-1. These data all support that UNC-43 triggers MADD-4B and NRX-1α, which act as anterograde signals to recruit postsynaptic GABAARs. Thus, our findings elucidate a mechanism for pre- and postsynaptic communication and inhibitory synaptic transmission and plasticity.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Animales , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Unión Neuromuscular/metabolismo , Sinapsis/metabolismo , Transmisión Sináptica/fisiología
18.
Ecotoxicol Environ Saf ; 255: 114812, 2023 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-36963186

RESUMEN

PM2.5 is a type of particulate matter with an aerodynamic diameter smaller than 2.5 µm, and exposure to PM2.5 can adversely damage human health. PM2.5 may impair health through oxidative stress, inflammatory reactions, immune function alterations and chromosome or DNA damage. Through increasing in-depth studies, researchers have found that noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs), circular RNAs (circRNAs) as well as long noncoding RNAs (lncRNAs), might play significant roles in PM2.5-related human diseases via some of the abovementioned mechanisms. Therefore, in this review, we mainly discuss the regulatory function of ncRNAs altered by PM2.5 in human diseases and summarize the potential molecular mechanisms. The findings reveal that these ncRNAs might induce or promote diseases via inflammation, the oxidative stress response, cell autophagy, apoptosis, cell junction damage, altered cell proliferation, malignant cell transformation, disruption of synaptic function and abnormalities in the differentiation and status of immune cells. Moreover, according to a bioinformatics analysis, the altered expression of potential genes caused by these ncRNAs might be related to the development of some human diseases. Furthermore, some ncRNAs, including lncRNAs, miRNAs and circRNAs, or processes in which they are involved may be used as biomarkers for relevant diseases and potential targets to prevent these diseases. Additionally, we performed a meta-analysis to identify more promising diagnostic ncRNAs as biomarkers for related diseases.


Asunto(s)
MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Circular/genética , MicroARNs/genética , MicroARNs/metabolismo , Inflamación , Biomarcadores , Material Particulado/toxicidad
19.
ACS Omega ; 7(41): 36904, 2022 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-36278109

RESUMEN

[This corrects the article DOI: 10.1021/acsomega.2c04064.].

20.
ACS Omega ; 7(38): 34420-34427, 2022 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-36188322

RESUMEN

Through thermodynamic calculation and high-temperature simulation experiments, the coupling behavior between gasification of high- and low-reactivity cokes and reduction of sintering ore in CO-N2-H2 mixed gas with 25% H2 volume fraction was studied, and the evolution of the coke carbon structure and the pore structure was analyzed. The results show that the reaction rate of the two cokes increases with the increase in temperature after the coupling reaction, and the strength after drumming decreases with the increase in temperature. The strength of low-reactivity coke after the reaction is higher than that of high-reactivity coke, and the reduction degree of sintering ore after the coupling reaction with low-reactivity coke is higher than that with high-reactivity coke. At high temperatures and high hydrogen-rich atmospheres with φ(H2) of 25%, the strength of high-reactivity coke after drum rotation is greater than 60.4%. The graphitization degree and carbon structure order of low-reactivity coke are higher than those of high-reactivity coke.

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