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1.
Nature ; 627(8003): 301-305, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38448596

RESUMEN

Solid-state Li-S batteries (SSLSBs) are made of low-cost and abundant materials free of supply chain concerns. Owing to their high theoretical energy densities, they are highly desirable for electric vehicles1-3. However, the development of SSLSBs has been historically plagued by the insulating nature of sulfur4,5 and the poor interfacial contacts induced by its large volume change during cycling6,7, impeding charge transfer among different solid components. Here we report an S9.3I molecular crystal with I2 inserted in the crystalline sulfur structure, which shows a semiconductor-level electrical conductivity (approximately 5.9 × 10-7 S cm-1) at 25 °C; an 11-order-of-magnitude increase over sulfur itself. Iodine introduces new states into the band gap of sulfur and promotes the formation of reactive polysulfides during electrochemical cycling. Further, the material features a low melting point of around 65 °C, which enables repairing of damaged interfaces due to cycling by periodical remelting of the cathode material. As a result, an Li-S9.3I battery demonstrates 400 stable cycles with a specific capacity retention of 87%. The design of this conductive, low-melting-point sulfur iodide material represents a substantial advancement in the chemistry of sulfur materials, and opens the door to the practical realization of SSLSBs.

2.
Nature ; 594(7862): 207-212, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34108699

RESUMEN

Chip floorplanning is the engineering task of designing the physical layout of a computer chip. Despite five decades of research1, chip floorplanning has defied automation, requiring months of intense effort by physical design engineers to produce manufacturable layouts. Here we present a deep reinforcement learning approach to chip floorplanning. In under six hours, our method automatically generates chip floorplans that are superior or comparable to those produced by humans in all key metrics, including power consumption, performance and chip area. To achieve this, we pose chip floorplanning as a reinforcement learning problem, and develop an edge-based graph convolutional neural network architecture capable of learning rich and transferable representations of the chip. As a result, our method utilizes past experience to become better and faster at solving new instances of the problem, allowing chip design to be performed by artificial agents with more experience than any human designer. Our method was used to design the next generation of Google's artificial intelligence (AI) accelerators, and has the potential to save thousands of hours of human effort for each new generation. Finally, we believe that more powerful AI-designed hardware will fuel advances in AI, creating a symbiotic relationship between the two fields.

3.
Nucleic Acids Res ; 52(7): 3510-3521, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38452220

RESUMEN

N6-Methyladenosine (m6A) is the most abundant chemical modification occurring on eukaryotic mRNAs, and has been reported to be involved in almost all stages of mRNA metabolism. The distribution of m6A sites is notably asymmetric along mRNAs, with a strong preference toward the 3' terminus of the transcript. How m6A regional preference is shaped remains incompletely understood. In this study, by performing m6A-seq on chromatin-associated RNAs, we found that m6A regional preference arises during transcription. Nucleosome occupancy is remarkedly increased in the region downstream of m6A sites, suggesting an intricate interplay between m6A methylation and nucleosome-mediated transcriptional dynamics. Notably, we found a remarkable slowdown of Pol-II movement around m6A sites. In addition, inhibiting Pol-II movement increases nearby m6A methylation levels. By analyzing massively parallel assays for m6A, we found that RNA secondary structures inhibit m6A methylation. Remarkably, the m6A sites associated with Pol-II pausing tend to be embedded within RNA secondary structures. These results suggest that Pol-II pausing could affect the accessibility of m6A motifs to the methyltransferase complex and subsequent m6A methylation by mediating RNA secondary structure. Overall, our study reveals a crucial role of transcriptional dynamics in the formation of m6A regional preference.


Asunto(s)
Adenosina , Adenosina/análogos & derivados , ARN Polimerasa II , ARN Mensajero , Transcripción Genética , Adenosina/metabolismo , Metilación , ARN Mensajero/metabolismo , ARN Mensajero/genética , ARN Polimerasa II/metabolismo , Humanos , Conformación de Ácido Nucleico , Nucleosomas/metabolismo , Nucleosomas/genética , Metiltransferasas/metabolismo , Metiltransferasas/genética , Cromatina/metabolismo , Cromatina/genética , Cromatina/química
4.
Proc Natl Acad Sci U S A ; 120(41): e2310714120, 2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37782794

RESUMEN

The future application of Li metal batteries (LMBs) at scale demands electrolytes that endow improved performance under fast-charging and low-temperature operating conditions. Recent works indicate that desolvation kinetics of Li+ plays a crucial role in enabling such behavior. However, the modulation of this process has typically been achieved through inducing qualitative degrees of ion pairing into the system. In this work, we find that a more quantitative control of the ion pairing is crucial to minimizing the desolvation penalty at the electrified interface and thus the reversibility of the Li metal anode under kinetic strain. This effect is demonstrated in localized electrolytes based on strongly and weakly bound ether solvents that allow for the deconvolution of solvation chemistry and structure. Unexpectedly, we find that maximum degrees of ion pairing are suboptimal for ultralow temperature and high-rate operation and that reversibility is substantially improved via slight local dilution away from the saturation point. Further, we find that at the optimum degree of ion pairing for each system, weakly bound solvents still produce superior behavior. The impact of these structure and chemistry effects on charge transfer are then explicitly resolved via experimental and computational analyses. Lastly, we demonstrate that the locally optimized diethyl ether-based localized-high-concentration electrolytes supports kinetic strained operating conditions, including cycling down to -60 °C and 20-min fast charging in LMB full cells. This work demonstrates that explicit, quantitative optimization of the Li+ solvation state is necessary for developing LMB electrolytes capable of low-temperature and high-rate operation.

5.
Nano Lett ; 24(1): 245-253, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38157424

RESUMEN

Mechanically strong and damage-tolerant corrosion protection layers are of great technological importance. However, corrosion protection layers with high modulus (>1.5 GPa) and tensile strength (>100 MPa) are rare. Here, we report that a 130 µm thick densified wood veneer with a Young's modulus of 34.49 GPa and tensile strength of 693 MPa exhibits both low diffusivity for metal ions and the ability of self-recovery from mechanical damage. Densified wood veneer is employed as an intermediate layer to render a mechanically strong corrosion protection structure, referred to as "wood corrosion protection structure", or WCPS. The corrosion rate of low-carbon steel protected by WCPS is reduced by 2 orders of magnitude than state-of-the-art corrosion protection layers during a salt spray test. The introduction of engineered wood veneer as a thin and mechanically strong material points to new directions of sustainable corrosion protection design.

6.
EMBO J ; 39(16): e103631, 2020 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-32643828

RESUMEN

Priming of synaptic vesicles involves Munc13-catalyzed transition of the Munc18-1/syntaxin-1 complex to the SNARE complex in the presence of SNAP-25 and synaptobrevin-2; Munc13 drives opening of syntaxin-1 via the MUN domain while Munc18-1 primes SNARE assembly via domain 3a. However, the underlying mechanism remains unclear. In this study, we have identified a number of residues in domain 3a of Munc18-1 that are crucial for Munc13 and Munc18-1 actions in SNARE complex assembly and synaptic vesicle priming. Our results showed that two residues (Q301/K308) at the side of domain 3a mediate the interaction between the Munc18-1/syntaxin-1 complex and the MUN domain. This interaction enables the MUN domain to drive the opening of syntaxin-1 linker region, thereby leading to the extension of domain 3a and promoting synaptobrevin-2 binding. In addition, we identified two residues (K332/K333) at the bottom of domain 3a that mediate the interaction between Munc18-1 and the SNARE motif of syntaxin-1. This interaction ensures Munc18-1 to persistently associate with syntaxin-1 during the conformational change of syntaxin-1 from closed to open, which reinforces the role of Munc18-1 in templating SNARE assembly. Taken together, our data suggest a mechanism by which Munc13 activates the Munc18-1/syntaxin-1 complex and enables Munc18-1 to prime SNARE assembly.


Asunto(s)
Proteínas Munc18 , Proteínas del Tejido Nervioso , Proteínas SNARE , Membranas Sinápticas , Sintaxina 1 , Animales , Células HEK293 , Humanos , Ratones , Proteínas Munc18/química , Proteínas Munc18/genética , Proteínas Munc18/metabolismo , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Dominios Proteicos , Ratas , Proteínas SNARE/química , Proteínas SNARE/genética , Proteínas SNARE/metabolismo , Membranas Sinápticas/química , Membranas Sinápticas/genética , Membranas Sinápticas/metabolismo , Sintaxina 1/química , Sintaxina 1/genética , Sintaxina 1/metabolismo
7.
Anal Chem ; 96(22): 9051-9059, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38776068

RESUMEN

Surface-enhanced Raman spectroscopy (SERS) tags have the advantages of unique fingerprint vibration spectrum, ultranarrow spectral line widths, and weak photobleaching effect, showing great potential for bioimaging. However, SERS imaging is still hindered for further application due to its weak spontaneous Raman scattering, biomolecular signal interference, and long acquisition times. Here, we develop a novel SERS tag of the core (Au)-shell (N-doped graphene) structure (Au@NGs) with ultrastrong and stable Raman signal (2180 cm-1) in the cellular Raman-silent region (1800-2800 cm-1) through base-promoted oxidative decarboxylation of amino acids. Exploring the factors (metal salts, amino acids, catalysts, temperature, etc.) to obtain Au@NGs with the strongest Raman signal commonly requires more than 100,000 separate experiments, while that using an orthogonal array testing strategy is reduced to 56. The existence of deep charge transfer between the Au surface and C≡N-graphene is proved by theoretical calculations, which means the ultrastrong signal of Au@NGs is the joint effect of electromagnetic and chemical enhancement. The Au@NGs have a detection sensitivity down to a single-nanoparticle level, and high-speed and high-resolution cellular imaging (4453 pixels) is obtained within 10 s by global Raman imaging. The combination of Au@NGs-based tags with ultrastrong intrinsic Raman imaging capability and global imaging technology holds great promise for high-speed Raman imaging.


Asunto(s)
Oro , Grafito , Espectrometría Raman , Espectrometría Raman/métodos , Oro/química , Grafito/química , Humanos , Nanopartículas del Metal/química , Propiedades de Superficie , Aminoácidos/análisis , Aminoácidos/química
8.
Biochem Biophys Res Commun ; 721: 150109, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38762932

RESUMEN

Wild-type Proteinase K binds to two Ca2+ ions, which play an important role in regulating enzymaticactivity and maintaining protein stability. Therefore, a predetermined concentration of Ca2+ must be added during the use of Proteinase K, which increases its commercial cost. Herein, we addressed this challenge using a computational strategy to engineer a Proteinase K mutant that does not require Ca2+ and exhibits high enzymatic activity and protein stability. In the absence of Ca2+, the best mutant, MT24 (S17W-S176N-D260F), displayed an activity approximately 9.2-fold higher than that of wild-type Proteinase K. It also exhibited excellent protein stability, retaining 56.2 % of its enzymatic activity after storage at 4 °C for 5 days. The residual enzymatic activity was 65-fold higher than that of the wild-type Proteinase K under the same storage conditions. Structural analysis and molecular dynamics simulations suggest that the introduction of new hydrogen bond and π-π stacking at the Ca2+ binding sites due to the mutation may be the reasons for the increased enzymatic activity and stability of MT24.


Asunto(s)
Calcio , Endopeptidasa K , Estabilidad de Enzimas , Simulación de Dinámica Molecular , Estabilidad Proteica , Endopeptidasa K/metabolismo , Endopeptidasa K/química , Calcio/metabolismo , Calcio/química , Diseño Asistido por Computadora , Mutación , Sitios de Unión , Ingeniería de Proteínas/métodos , Conformación Proteica
9.
Opt Express ; 32(6): 10419-10428, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38571254

RESUMEN

Twisted stacking of two-dimensional materials with broken inversion symmetry, such as spiral MoTe2 nanopyramids and supertwisted spiral WS2, emerge extremely strong second- and third-harmonic generation. Unlike well-studied nonlinear optical effects in these newly synthesized layered materials, photoluminescence (PL) spectra and exciton information involving their optoelectronic applications remain unknown. Here, we report layer- and power-dependent PL spectra of the supertwisted spiral WS2. The anomalous layer-dependent PL evolutions that PL intensity almost linearly increases with the rise of layer thickness have been determined. Furthermore, from the power-dependent spectra, we find the power exponents of the supertwisted spiral WS2 are smaller than 1, while those of the conventional multilayer WS2 are bigger than 1. These two abnormal phenomena indicate the enlarged interlayer spacing and the decoupling interlayer interaction in the supertwisted spiral WS2. These observations provide insight into PL features in the supertwisted spiral materials and may pave the way for further optoelectronic devices based on the twisted stacking materials.

10.
Cardiovasc Diabetol ; 23(1): 16, 2024 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-38184577

RESUMEN

BACKGROUND: Findings from earlier research have established that insulin resistance (IR) is implicated in atherosclerosis progression, representing a noteworthy risk factor for cardiovascular disease (CVD). Recently, the triglyceride glucose-body mass index (TyG-BMI) has been introduced as a straightforward and robust alternative indicator for early detection of IR. Nevertheless, there is a scarcity of studies that have examined the capability of TyG-BMI for predicting incident CVD. Consequently, the core objective of this study was to determine whether the cumulative average TyG-BMI correlated with CVD incidence. METHODS: All data was sourced from the China Health and Retirement Longitudinal Study (CHARLS). The exposure was the cumulative average TyG-BMI, determined by the average of TyG-BMI values for the baseline and follow-up investigations (Wave 1 in 2011, Wave 3 in 2015, respectively). The calculation of TyG-BMI involved a combination of triglyceride, fasting blood glucose, and body mass index. The primary outcome was incident CVD. Logistic regression analyses as well as restricted cubic spline (RCS) regression analyses were performed for examining the association between the cumulative average TyG-BMI and CVD incidence. RESULTS: In all, 5,418 participants were enrolled in our analysis, with 2,904 (53.6%) being female, and a mean (standard deviation, SD) age of 59.6 (8.8) years. The mean (SD) cumulative average TyG-BMI among all participants was 204.9 (35.7). Totally, during a 4-year follow-up, 543 (10.0%) participants developed CVD. The fully adjusted logistic regression analysis revealed a significant association between the cumulative average TyG-BMI and incident CVD [odds ratio (OR), 95% confidence interval (CI): 1.168, 1.040-1.310, per 1 SD increase]. The RCS regression analysis displayed a positive, linear association of the cumulative average TyG-BMI with CVD incidence (P for overall = 0.038, P for nonlinear = 0.436). CONCLUSIONS: Our study revealed a noteworthy correlation between the cumulative average TyG-BMI and incident CVD among the middle-aged and older population. The cumulative average TyG-BMI emerges as a valuable tool that may enhance the primary prevention and treatment of CVD.


Asunto(s)
Enfermedades Cardiovasculares , Resistencia a la Insulina , Persona de Mediana Edad , Femenino , Humanos , Anciano , Masculino , Incidencia , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Índice de Masa Corporal , Estudios de Cohortes , Estudios Longitudinales , Estudios Prospectivos , China/epidemiología , Glucosa
11.
BMC Cardiovasc Disord ; 24(1): 160, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38491412

RESUMEN

OBJECTIVE: Dyslipidemia is a co-existing problem in patients with diabetes mellitus (DM) and coronary artery disease (CAD), and apolipoprotein E (APOE) plays an important role in lipid metabolism. However, the relationship between the APOE gene polymorphisms and the risk of developing CAD in type 2 DM (T2DM) patients remains controversial. The aim of this study was to assess this relationship and provide a reference for further risk assessment of CAD in T2DM patients. METHODS: The study included 378 patients with T2DM complicated with CAD (T2DM + CAD) and 431 patients with T2DM alone in the case group, and 351 individuals without DM and CAD were set as controls. The APOE rs429358 and rs7412 polymorphisms were genotyped by polymerase chain reaction (PCR) - microarray. Differences in APOE genotypes and alleles between patients and controls were compared. Multiple logistic regression analysis was performed after adjusting for age, gender, body mass index (BMI), history of smoking, and history of drinking to access the relationship between APOE genotypes and T2DM + CAD risk. RESULTS: The frequencies of the APOE ɛ3/ɛ4 genotype and ε4 allele were higher in the T2DM + CAD patients, and the frequencies of the APOE ɛ3/ɛ3 genotype and ε3 allele were lower than those in the controls (all p < 0.05). The T2DM + CAD patients with ɛ4 allele had higher level in low-density lipoprotein cholesterol (LDL-C) than those in patients with ɛ2 and ɛ3 allele (p < 0.05). The results of logistic regression analysis showed that age ≥ 60 years old, and BMI ≥ 24.0 kg/m2 were independent risk factors for T2DM and T2DM + CAD, and APOE ɛ3/ɛ4 genotype (adjusted odds ratio (OR) = 1.93, 95% confidence interval (CI) = 1.18-3.14, p = 0.008) and ɛ4 allele (adjusted OR = 1.97, 95% CI = 1.23-3.17) were independent risk factors for T2DM + CAD. However, the APOE genotypes and alleles were not found to have relationship with the risk of T2DM. CONCLUSIONS: APOE ε3/ε4 genotype and ε4 allele were independent risk factors for T2DM complicated with CAD, but not for T2DM.


Asunto(s)
Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Humanos , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Apolipoproteínas E/genética , Genotipo , Factores de Riesgo , Apolipoproteína E3/genética , Alelos
12.
Am J Respir Crit Care Med ; 207(3): 323-335, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36191258

RESUMEN

Rationale: Obstructive sleep apnea (OSA)-induced endothelial cell (EC) dysfunction contributes to OSA-related cardiovascular sequelae. The mechanistic basis of endothelial impairment by OSA is unclear. Objectives: The goals of this study were to identify the mechanism of OSA-induced EC dysfunction and explore the potential therapies for OSA-accelerated cardiovascular disease. Methods: The experimental methods include data mining, bioinformatics, EC functional analyses, OSA mouse models, and assessment of OSA human subjects. Measurements and Main Results: Using mined microRNA sequencing data, we found that microRNA 210 (miR-210) conferred the greatest induction by intermittent hypoxia in ECs. Consistently, the serum concentration of miR-210 was higher in individuals with OSA from two independent cohorts. Importantly, miR-210 concentration was positively correlated with the apnea-hypopnea index. RNA sequencing data collected from ECs transfected with miR-210 or treated with OSA serum showed a set of genes commonly altered by miR-210 and OSA serum, which are largely involved in mitochondrion-related pathways. ECs transfected with miR-210 or treated with OSA serum showed reduced [Formula: see text]o2 rate, mitochondrial membrane potential, and DNA abundance. Mechanistically, intermittent hypoxia-induced SREBP2 (sterol regulatory element-binding protein 2) bound to the promoter region of miR-210, which in turn inhibited the iron-sulfur cluster assembly enzyme and led to mitochondrial dysfunction. Moreover, the SREBP2 inhibitor betulin alleviated intermittent hypoxia-increased systolic blood pressure in the OSA mouse model. Conclusions: These results identify an axis involving SREBP2, miR-210, and mitochondrial dysfunction, representing a new mechanistic link between OSA and EC dysfunction that may have important implications for treating and preventing OSA-related cardiovascular sequelae.


Asunto(s)
Enfermedades Cardiovasculares , MicroARNs , Apnea Obstructiva del Sueño , Enfermedades Vasculares , Animales , Ratones , Humanos , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/genética , Hipoxia/genética , MicroARNs/genética
13.
J Community Health ; 49(1): 34-45, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37382837

RESUMEN

The well-being of primary care clinicians represents an area of increasing interest amid concerns that the COVID-19 pandemic may have exacerbated already high prevalence rates of clinician burnout. This retrospective cohort study was designed to identify demographic, clinical, and work-specific factors that may have contributed to newly acquired burnout after the onset of the COVID-19 pandemic. An anonymous web-based questionnaire distributed in August 2020 to New York State (NYS) primary care clinicians, via email outreach and newsletters, produced 1,499 NYS primary care clinician survey respondents. Burnout assessment was measured pre-pandemic and early in the pandemic using a validated single-item question with a 5-point scale ranging from (1) enjoy work to (5) completely burned out. Demographic and work factors were assessed via the self-reporting questionnaire. Thirty percent of 1,499 survey respondents reported newly acquired burnout during the early pandemic period. This was more often reported by clinicians who were women, were younger than 56 years old, had adult dependents, practiced in New York City, had dual roles (patient care and administration), and were employees. Lack of control in the workplace prior to the pandemic was predictive of burnout early in the pandemic, while work control changes experienced following the pandemic were associated with newly acquired burnout. Low response rate and potential recall bias represent limitations. These findings demonstrate that reporting of burnout increased among primary care clinicians during the pandemic, partially due to varied and numerous work environment and systemic factors.


Asunto(s)
COVID-19 , Pandemias , Adulto , Femenino , Humanos , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , COVID-19/epidemiología , Agotamiento Psicológico , Ciudad de Nueva York/epidemiología , Atención Primaria de Salud , Encuestas y Cuestionarios
14.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-33753508

RESUMEN

As the core component of the adherens junction in cell-cell adhesion, the cadherin-catenin complex transduces mechanical tension between neighboring cells. Structural studies have shown that the cadherin-catenin complex exists as an ensemble of flexible conformations, with the actin-binding domain (ABD) of α-catenin adopting a variety of configurations. Here, we have determined the nanoscale protein domain dynamics of the cadherin-catenin complex using neutron spin echo spectroscopy (NSE), selective deuteration, and theoretical physics analyses. NSE reveals that, in the cadherin-catenin complex, the motion of the entire ABD becomes activated on nanosecond to submicrosecond timescales. By contrast, in the α-catenin homodimer, only the smaller disordered C-terminal tail of ABD is moving. Molecular dynamics (MD) simulations also show increased mobility of ABD in the cadherin-catenin complex, compared to the α-catenin homodimer. Biased MD simulations further reveal that the applied external forces promote the transition of ABD in the cadherin-catenin complex from an ensemble of diverse conformational states to specific states that resemble the actin-bound structure. The activated motion and an ensemble of flexible configurations of the mechanosensory ABD suggest the formation of an entropic trap in the cadherin-catenin complex, serving as negative allosteric regulation that impedes the complex from binding to actin under zero force. Mechanical tension facilitates the reduction in dynamics and narrows the conformational ensemble of ABD to specific configurations that are well suited to bind F-actin. Our results provide a protein dynamics and entropic explanation for the observed force-sensitive binding behavior of a mechanosensitive protein complex.


Asunto(s)
Cadherinas/química , Cateninas/química , Sitios de Unión , Humanos , Espectroscopía de Resonancia Magnética , Simulación de Dinámica Molecular , Movimiento (Física) , Neutrones , Dominios Proteicos
15.
BMC Biol ; 21(1): 158, 2023 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-37443000

RESUMEN

BACKGROUND: Neurotransmitter release depends on the fusion of synaptic vesicles with the presynaptic membrane and is mainly mediated by SNARE complex assembly. During the transition of Munc18-1/Syntaxin-1 to the SNARE complex, the opening of the Syntaxin-1 linker region catalyzed by Munc13-1 leads to the extension of the domain 3a hinge loop, which enables domain 3a to bind SNARE motifs in Synaptobrevin-2 and Syntaxin-1 and template the SNARE complex assembly. However, the exact mechanism of domain 3a extension remains elusive. RESULTS: Here, we characterized residues on the domain 3a hinge loop that are crucial for the extension of domain 3a by using biophysical and biochemical approaches and electrophysiological recordings. We showed that the mutation of residues T323/M324/R325 disrupted Munc13-1-mediated SNARE complex assembly and membrane fusion starting from Munc18-1/Syntaxin-1 in vitro and caused severe defects in the synaptic exocytosis of mouse cortex neurons in vivo. Moreover, the mutation had no effect on the binding of Synaptobrevin-2 to isolated Munc18-1 or the conformational change of the Syntaxin-1 linker region catalyzed by the Munc13-1 MUN domain. However, the extension of the domain 3a hinge loop in Munc18-1/Syntaxin-1 was completely disrupted by the mutation, leading to the failure of Synaptobrevin-2 binding to Munc18-1/Syntaxin-1. CONCLUSIONS: Together with previous results, our data further support the model that the template function of Munc18-1 in SNARE complex assembly requires the extension of domain 3a, and particular residues in the domain 3a hinge loop are crucial for the autoinhibitory release of domain 3a after the MUN domain opens the Syntaxin-1 linker region.


Asunto(s)
Proteínas del Tejido Nervioso , Proteína 2 de Membrana Asociada a Vesículas , Ratones , Animales , Proteínas del Tejido Nervioso/genética , Proteína 2 de Membrana Asociada a Vesículas/genética , Proteína 2 de Membrana Asociada a Vesículas/metabolismo , Sintaxina 1/genética , Sintaxina 1/química , Sintaxina 1/metabolismo , Proteínas Qa-SNARE/genética , Proteínas Qa-SNARE/metabolismo , Proteínas SNARE/metabolismo , Unión Proteica
16.
Sensors (Basel) ; 24(9)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38732808

RESUMEN

Currently, surface EMG signals have a wide range of applications in human-computer interaction systems. However, selecting features for gesture recognition models based on traditional machine learning can be challenging and may not yield satisfactory results. Considering the strong nonlinear generalization ability of neural networks, this paper proposes a two-stream residual network model with an attention mechanism for gesture recognition. One branch processes surface EMG signals, while the other processes hand acceleration signals. Segmented networks are utilized to fully extract the physiological and kinematic features of the hand. To enhance the model's capacity to learn crucial information, we introduce an attention mechanism after global average pooling. This mechanism strengthens relevant features and weakens irrelevant ones. Finally, the deep features obtained from the two branches of learning are fused to further improve the accuracy of multi-gesture recognition. The experiments conducted on the NinaPro DB2 public dataset resulted in a recognition accuracy of 88.25% for 49 gestures. This demonstrates that our network model can effectively capture gesture features, enhancing accuracy and robustness across various gestures. This approach to multi-source information fusion is expected to provide more accurate and real-time commands for exoskeleton robots and myoelectric prosthetic control systems, thereby enhancing the user experience and the naturalness of robot operation.


Asunto(s)
Electromiografía , Gestos , Redes Neurales de la Computación , Humanos , Electromiografía/métodos , Procesamiento de Señales Asistido por Computador , Reconocimiento de Normas Patrones Automatizadas/métodos , Aceleración , Algoritmos , Mano/fisiología , Aprendizaje Automático , Fenómenos Biomecánicos/fisiología
17.
Nano Lett ; 23(9): 3769-3774, 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37129232

RESUMEN

High-resolution patterning of perovskite quantum dots (PQDs) is of significant importance for satisfying various practical applications, including high-resolution displays and image sensing. However, due to the limitation of the instability of PQDs, the existing patterning strategy always involves chemical reagent treatment or mask contact that is not suitable for PQDs. Therefore, it is still a challenge to fabricate high-resolution full-color PQD arrays. Here, we present a femtosecond laser-induced forward transfer (FsLIFT) technology, which enables the programmable fabrication of high-resolution full-color PQD arrays and arbitrary micropatterns. The FsLIFT process integrates transfer, deposition, patterning, and alignment in one step without involving a mask and chemical reagent treatment, guaranteeing the preservation of the photophysical properties of PQDs. A full-color PQD array with a high resolution of 2 µm has been successfully achieved. We anticipate that our facile and flexible FsLIFT technology can facilitate the development of diverse practical applications based on patterned PQDs.

18.
Medicina (Kaunas) ; 60(2)2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38399483

RESUMEN

Background and Objectives: Optimal opioid analgesia is an excellent analgesia that does not present unexpected adverse effects. Nalbuphine, acting on the opioid receptor as a partial mu antagonist and kappa agonist, is considered a suitable option for patients undergoing laparoscopic surgery. Therefore, we aim to investigate the appropriate dosage of nalbuphine for post-operative pain management in patients with laparoscopic cholecystectomy. Materials and Methods: Patients were randomly categorized into low, medium, and high nalbuphine groups. In each group, a patient control device for post-operative pain control was programed with a low (0.05 mg/kg), medium (0.10 mg/kg), or high (0.20 mg/kg) nalbuphine dose as a loading dose and each bolus dose with a lockout interval of 7 min and without background infusion. Primary and secondary outcomes included the post-operative pain scale and nalbuphine consumption, and episodes of post-operative opioid-related adverse events and satisfactory scores. Results: The low-dosage group presented a higher initial self-reported pain score in comparison to the other two groups for the two hours post-op (p = 0.039) but presented lower nalbuphine consumption than the other two groups for four hours post-op (p = 0.047). There was no significant difference in the analysis of the satisfactory score and adverse events. Conclusions: An appropriate administration of nalbuphine could be 0.1 to 0.2 mg/kg at the initial four hours; this formula could be modified to a lower dosage (0.05 mg/kg) in the post-operative management of laparoscopic cholecystectomy.


Asunto(s)
Analgesia , Colecistectomía Laparoscópica , Nalbufina , Humanos , Nalbufina/efectos adversos , Analgésicos Opioides/efectos adversos , Colecistectomía Laparoscópica/efectos adversos , Dolor Postoperatorio/tratamiento farmacológico
19.
J Am Chem Soc ; 145(17): 9624-9633, 2023 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-37071778

RESUMEN

Sulfurized polyacrylonitrile (SPAN) represents a class of sulfur-bonded polymers, which have shown thousands of stable cycles as a cathode in lithium-sulfur batteries. However, the exact molecular structure and its electrochemical reaction mechanism remain unclear. Most significantly, SPAN shows an over 25% 1st cycle irreversible capacity loss before exhibiting perfect reversibility for subsequent cycles. Here, with a SPAN thin-film platform and an array of analytical tools, we show that the SPAN capacity loss is associated with intramolecular dehydrogenation along with the loss of sulfur. This results in an increase in the aromaticity of the structure, which is corroborated by a >100× increase in electronic conductivity. We also discovered that the conductive carbon additive in the cathode is instrumental in driving the reaction to completion. Based on the proposed mechanism, we have developed a synthesis procedure to eliminate more than 50% of the irreversible capacity loss. Our insights into the reaction mechanism provide a blueprint for the design of high-performance sulfurized polymer cathode materials.

20.
Cardiovasc Diabetol ; 22(1): 150, 2023 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-37365588

RESUMEN

BACKGROUND: The potential predictive significance of atherogenic index of plasma (AIP) for cardiovascular outcomes in patients with acute coronary syndrome (ACS) and who have undergone percutaneous coronary intervention (PCI), with low-density lipoprotein-cholesterol (LDL-C) below 1.8mmol/L, has not been well explored. METHODS: The retrospective cohort analysis included 1,133 patients with ACS and LDL-C levels below 1.8mmol/L who underwent PCI. AIP is calculated as log (triglyceride/high-density lipoprotein-cholesterol). Patients were divided into two groups according to the median value of AIP. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, nonfatal myocardial infarction, ischemic stroke or unplanned repeat revascularization. The association between AIP and the prevalence of MACCE was evaluated using multivariable Cox proportional hazard models. RESULTS: Over a median follow-up of 26 months, the incidence of MACCE was higher in the high AIP group compared to the low AIP group (9.6% vs. 6.0%, P log-rank = 0.020), and the difference was mainly derived from an increased risk of unplanned repeat revascularization (7.6% vs. 4.6%, P log-rank = 0.028). After adjusting for multiple variables, elevated AIP was independently associated with an increased risk of MACCE, regardless of whether AIP was considered a nominal or continuous variable (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.04-2.53 or HR 2.01, 95% CI 1.09-3.73). CONCLUSIONS: The present study demonstrates that AIP is a significant predictor of adverse outcomes in ACS patients undergoing PCI with LDL-C < 1.8mmol/L. These results suggest that AIP may offer supplementary prognostic information for ACS patients with optimally managed LDL-C levels.


Asunto(s)
Síndrome Coronario Agudo , Aterosclerosis , Intervención Coronaria Percutánea , Humanos , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/terapia , LDL-Colesterol , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
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