ABSTRACT
Excessive accumulation of reduced nicotinamide adenine dinucleotide (NADH) within biological organisms is closely associated with many diseases. It remains a challenge to efficiently convert superfluous and detrimental NADH to NAD+. NADH oxidase (NOX) is a crucial oxidoreductase that catalyzes the oxidation of NADH to NAD+. Herein, M1M2 (Mi=V/Mn/Fe/Co/Cu/Mo/Rh/Ru/Pd, i = 1 or 2) mated-atom nanozymes (MANs) are designed by mimicking natural enzymes with polymetallic active centers. Excitingly, RhCo MAN possesses excellent and sustainable NOX-like activity, with Km-NADH (16.11 µM) being lower than that of NOX-mimics reported so far. Thus, RhCo MAN can significantly promote the regeneration of NAD+ and regulate macrophage polarization toward the M2 phenotype through down-regulation of TLR4 expression, which may help to recover skin regeneration. However, RhRu MAN with peroxidase-like activity and RhMn MAN with superoxide dismutase-like activity exhibit little modulating effects on eczema. This work provides a new strategy to inhibit skin inflammation and promote skin regeneration.
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This study proposes a high-sensitivity resonant graphene accelerometer based on a pressure-induced sensing mechanism. The accelerometer design encompasses an optical fiber and a vacuum-sealed graphene resonator affixed to a silicon sensitive film, incorporating a proof mass. This indirect sensing mechanism effectively mitigates the vibration mode aliasing of graphene and the proof mass while ensuring a minimal energy loss in the operating resonator. The mechanical vibration of graphene is excited and detected through an all-fiber optical system. Notably, the proposed sensor demonstrates a sensitivity of 34.3â kHz/g within the range of 0-3.5â g, which is eight times higher than comparable accelerometers utilizing a proof mass on a graphene membrane. This work exhibits a novel, to the best of our knowledge, approach to an acceleration measurement using 2D resonators, exhibiting distinct advantages in terms of compact size and heightened sensitivity.
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BACKGROUND: Normal bile is sterile. Studies have shown that cholangitis after liver transplantation (LT) was associated with a relatively poor prognosis. It remains unclear whether the bacteriobilia or fungibilia impact the patient outcomes in LT recipients, especially with donation after circulatory death (DCD) allografts, which was correlated with a higher risk of allograft failure. METHODS: This retrospective study included 139 LT recipients of DCD grafts from 2019 to 2021. All patients were divided into two groups according to the presence or absence of bacteriobilia or fungibilia. The prevalence and microbial spectrum of postoperative bacteriobilia or fungibilia and its possible association with outcomes, especially hospital stay were analyzed. RESULTS: Totally 135 and 171 organisms were isolated at weeks 1 and 2, respectively. Among all patients included in this analysis, 83 (59.7%) developed bacteriobilia or fungibilia within 2 weeks post-transplantation. The occurrence of bacteriobilia or fungibilia (ß = 7.43, 95% CI: 0.02 to 14.82, P = 0.049), particularly the detection of Pseudomonas (ß = 18.84, 95% CI: 6.51 to 31.07, P = 0.003) within 2 weeks post-transplantation was associated with a longer hospital stay. However, it did not affect the graft and patient survival. CONCLUSIONS: The occurrence of bacteriobilia or fungibilia, particularly Pseudomonas within 2 weeks post-transplantation, could influence the recovery of liver function and was associated with prolonged hospital stay but not the graft and patient survival.
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Background and Objectives: This study examined whether the decline in people's adoption of personal NPIs (e.g., mask wearing) results from the preclusion by vaccination. This study also incorporates the concepts of risk perception and the risk-as-feelings model to elucidate the possible mechanisms behind this preclusion. Materials and Methods: Two cross-sectional surveys (N = 462 in Survey 1 and N = 505 in Survey 2) were administered before and during the first outbreak of COVID-19 in Taiwan. The survey items were designed to measure participants' perceived severity of COVID-19, worry about COVID-19, intention to adopt personal NPIs, and attitudes toward COVID-19 vaccines. Utilizing the risk perception framework, we conducted multigroup SEM (Structural Equation Modeling) to construct the optimal structural model for both samples. Results and Conclusions: The multigroup SEM results showed that worry (i.e., the emotional component of risk perception) fully mediates the influence of the perceived severity of COVID-19 (i.e., the cognitive component of risk perception) on the intention to adopt NPIs in both surveys [z = 4.03, p < 0.001 for Survey 1 and z = 2.49, p < 0.050 for Survey 2]. Before the outbreak (i.e., Survey 1), people's attitudes toward COVID-19 vaccines showed no significant association with their worry about COVID-19 [z = 0.66, p = 0.508]. However, in Survey 2, following the real outbreak of COVID-19, people's attitudes toward COVID-19 vaccines negatively predicts their worry about COVID-19 [z = -4.31, p < 0.001], indirectly resulting in a negative effect on their intention to adopt personal NPIs. This suggests the occurrence of the Peltzman effect. That is, vaccination fosters a sense of safety, subsequently diminishing alertness to COVID-19, and thus reducing the intention to adopt personal NPIs.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , COVID-19 Vaccines/therapeutic use , Masks , Cross-Sectional Studies , VaccinationABSTRACT
Two-dimensional (2D) Ti3C2Tx MXene materials show great potential in electrochemical and flexible sensors due to their high electrical conductivity, good chemical stability, and special delaminated structure. However, their thermal properties were rarely studied, which remarkably affect the stability and safety of various devices. Here, we fabricated a suspended MXene drum resonator photothermally driven by a sinusoidally modulated laser, measured the thermal time constant by demodulating the thermomechanical motion, and then calculated the thermal conductivity and thermal diffusivity of the MXene film. Experiments show the thermal conductivity of the film increases from 3.10 to 3.58 W/m·K while the thermal diffusivity from 1.06 × 10-6 to 1.22 × 10-6 m2/s when temperature increases from 300 to 360 K. We also confirm the film thermal conductivity is mainly contributed by phonon transport rather than electron transport. Furthermore, the relationship between the mechanical and thermal properties of the MXene films was disclosed. The thermal conductivity decreases when film strain increases, caused by enhanced phonon scattering and softening of high-frequency phonons. The measurements provide a noninvasive method to analyze the thermal characteristics of suspended MXene films, which can be further extended to the thermal properties of other 2D materials.
ABSTRACT
Nanomechanical resonators made of suspended graphene exhibit high sensitivity to pressure changes. Nevertheless, the graphene resonator pressure performance is affected owing to the gas permeation problem between the graphene film and the substrate. Therefore, we prepared edge-deposited graphene resonators by focused ion beam (FIB) deposition of SiO2, and their gas leakage velocities and pressure-sensing ability were demonstrated. In this paper, we characterize the pressure-sensing response and gas leakage velocities of graphene membranes using an all-optical actuation system. The gas leakage velocities of graphene resonators with diameters of 10, 20, and 40 µm are reduced by 5.0 × 106, 2.0 × 107, and 8.1 × 107 atoms/s, respectively, which demonstrates that the edge deposition structure can reduce the gas leakage of the resonator. Furthermore, the pressure-sensing performance of three graphene resonators with different diameters was evaluated, and their average pressure sensitivities were calculated to be 3.4, 2.4, and 1.9 kHz/kPa, with the largest full-range hysteresis errors of 0.6, 0.7, and 1.0%, respectively. The temperature stabilities of the three sizes of resonators in the temperature range of 300-400 K are 0.016, 0.015, and 0.016%/K, and the maximum resonance frequency drift over 1 h is 0.0058, 0.0048, and 0.0112%, respectively. This work has great significance for the improvement of gas leakage velocity characterization of graphene membrane and graphene resonant pressure sensor performance optimization.
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Benign familial infantile seizure (BFIS) is an autosomal dominant infantile-onset epilepsy syndrome with a typically benign prognosis. It is commonly associated with heterozygous mutations of the PRRT2 gene located on chromosome 16p11.2. The frameshift heterozygous mutation (c.649dupC, p.Arg217Profs∗8) in PRRT2 is responsible for the majority of BFIS cases. In this report, we present a rare case of a girl with a confirmed clinical and genetic diagnosis of BFIS due to a frameshift heterozygous mutation in PRRT2 (c.649dupC). She exhibited typical neurodevelopment until 15 months of age, followed by an unexpected severe autistic regression. In addition to BFIS, PRRT2 mutations are also associated with paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions and paroxysmal choreoathetosis (ICCA), indicating a complex genotype-phenotype heterogeneity in PRRT2 mutations. This clinical observation highlights the possibility that BFIS patients with PRRT2 mutations may not always have a benign neurodevelopmental prognosis, emphasizing the need for long-term clinical follow-up.
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A total of twenty-two diterpenoid alkaloids, including ten unprecedented ones, namely refractines C-L, were isolated from the roots of Aconitum refractum (Finet et Gagnep.) Hand.-Mazz. Refractine C was the first example of a natural diterpenoid alkaloid wherein C-19 is linked to N position by an oxaziridine ring. Refractine L was a rare glycosidic diterpenoid alkaloid with fructofuranoside. Most of the isolated compounds obtained from a previous study were screened for their anti-inflammatory and myocardial protective activities. The autophagy-inducing effects of some of these compounds on RAW 264.7 cells were evaluated by assessing the expression of microtubule-associated protein 1 light chain 3 (LC3-II/LC3-I). Results revealed that some compounds exerted varying levels of inhibitory effects on the proliferative activity of RAW 264.7 cells.
Subject(s)
Aconitum , Alkaloids , Autophagy , Diterpenes , Aconitum/chemistry , Mice , Animals , Autophagy/drug effects , RAW 264.7 Cells , Alkaloids/pharmacology , Alkaloids/isolation & purification , Alkaloids/chemistry , Diterpenes/pharmacology , Diterpenes/chemistry , Diterpenes/isolation & purification , Cell Proliferation/drug effects , Molecular Structure , Structure-Activity Relationship , Dose-Response Relationship, Drug , Plant Roots/chemistryABSTRACT
Introduction: Tuberculosis (TB) stands as a paramount global health concern, contributing significantly to worldwide mortality rates. Effective containment of TB requires deployment of cost-efficient screening method with limited resources. To enhance the precision of resource allocation in the global fight against TB, this research proposed chest X-ray radiography (CXR) based machine learning screening algorithms with optimization, benchmarking and tuning for the best TB subclassification tasks for clinical application. Methods: This investigation delves into the development and evaluation of a robust ensemble deep learning framework, comprising 43 distinct models, tailored for the identification of active TB cases and the categorization of their clinical subtypes. The proposed framework is essentially an ensemble model with multiple feature extractors and one of three fusion strategies-voting, attention-based, or concatenation methods-in the fusion stage before a final classification. The comprised de-identified dataset contains records of 915 active TB patients alongside 1,276 healthy controls with subtype-specific information. Thus, the realizations of our framework are capable for diagnosis with subclass identification. The subclass tags include: secondary tuberculosis/tuberculous pleurisy; non-cavity/cavity; secondary tuberculosis only/secondary tuberculosis and tuberculous pleurisy; tuberculous pleurisy only/secondary tuberculosis and tuberculous pleurisy. Results: Based on the dataset and model selection and tuning, ensemble models show their capability with self-correction capability of subclass identification with rendering robust clinical predictions. The best double-CNN-extractor model with concatenation/attention fusion strategies may potentially be the successful model for subclass tasks in real application. With visualization techniques, in-depth analysis of the ensemble model's performance across different fusion strategies are verified. Discussion: The findings underscore the potential of such ensemble approaches in augmenting TB diagnostics with subclassification. Even with limited dataset, the self-correction within the ensemble models still guarantees the accuracies to some level for potential clinical decision-making processes in TB management. Ultimately, this study shows a direction for better TB screening in the future TB response strategy.
ABSTRACT
Lipid nanoparticles (LNPs) are drug carriers for protecting nucleic acids for cellular delivery. The first mRNA vaccines authorized by the United States Food and Drug Administration are the mRNA-1273 (Moderna) and BNT162b (BioNTech/Pfizer) vaccines against coronavirus disease 2019 (COVID-19). We designed a 3D printed Omnidirectional Sheath-flow Enabled Microfluidics (OSEM) device for producing mRNA-loaded LNPs that closely resemble the Moderna vaccine: we used the same lipid formulations to encapsulate mRNA encoding SARS-CoV-2 spike protein. The OSEM device is made of durable methacrylate-based materials that can support flow rates in the mL min-1 range and was fabricated by stereolithography (SLA), incorporating readily adaptable interfaces using commercial fluidic connectors. Two key features of the OSEM device are: 1) a 4-way hydrodynamic flow focusing region and 2) a staggered herringbone mixer (SHM). Superior to conventional planar fluid junctions, the 4-way sheath flow channel generates an evenly focused, circular center flow that facilitates the formation of LNPs with low polydispersity. Downstream, fluid mixing in the SHM is intensified by incorporating a zig-zag fluidic pathway to deliver high mRNA encapsulation efficiency. We characterized the mRNA-loaded LNPs produced in the OSEM device and showed that the enhanced 3D microfluidic structures enable a 5-fold higher throughput production rate (60 mL min-1) of LNPs compared to commercial multi-thousand-dollar micromixers. The device produced LNPs of diameter less than 90 nm, with low polydispersity (2-8%) and high mRNA encapsulation efficiency (>90%). The 3D-printed device provides a cost-effective and easily prepared solution for high-throughput LNP production.
Subject(s)
COVID-19 , Nanoparticles , United States , Humans , Spike Glycoprotein, Coronavirus/genetics , RNA, Messenger/genetics , SARS-CoV-2/genetics , Nanoparticles/chemistry , Liposomes , Lab-On-A-Chip Devices , Printing, Three-DimensionalABSTRACT
Electrochemical reduction of CO2 to multicarbon (C2+) products with added value represents a promising strategy for achieving a carbon-neutral economy. Precise manipulation of the catalytic interface is imperative to control the catalytic selectivity, particularly toward C2+ products. In this study, a unique Cu/UIO-Br interface is designed, wherein the Cu(111) plane is co-modified simultaneously by Br and O from UIO-66-Br support. Such Cu/UIO-Br catalytic interface demonstrates a superior Faradaic efficiency of ≈53% for C2+ products (ethanol/ethylene) and the C2+ partial current density reached 24.3 mA cm-2 in an H-cell electrolyzer. The kinetic isotopic effect test, in situ attenuated total reflection Fourier transform infrared spectroscopy and density functional theory calculations have been conducted to elucidate the catalytic mechanism. The Br, O co-modification on the Cu(111) interface enhanced the adsorption of CO2 species. The hydrogen-bond effect from the doped Br atom regulated the kinetic processes of *H species in CO2RR and promoted the formation of *COH intermediate. The formed *COH facilitates the *CO-*COH coupling and promotes the C2+ selectivity finally. This comprehensive investigation not only provides an in-depth study and understanding of the catalytic process but also offers a promising strategy for designing efficient Cu-based catalysts with exceptional C2+ products.
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The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.
Subject(s)
COVID-19 , Communicable Diseases , Cross Infection , Humans , Artificial Intelligence , COVID-19/prevention & control , HospitalsABSTRACT
Linusorbs (LOs), significantly influence oil quality and sensory properties of flaxseed oil. Trp-containing LOs exhibit distinct oxidative behavior when γ-tocopherol (γ-T) is present. Polar fractions of crude flaxseed oil were stripped via silica absorption, and reintroduced (LO and γ-T) separately into the oil matrix to investigate their interaction during storage. Compared with crude oil, LOs account for 18.49% reduction of p-anisidine value, while LOs with γ-T contributed to most of the endogenous antioxidant effect in crude oil. γ-T was found to suppress oxidation of Trp-containing LO at early stage (Met form), while facilitate oxidation while at their mid-stage (MetO form, Methionine sulfoxide). In vitro oxidation shows that CLD more likely cleaved into peptide fragments, while few products retain intact ring structures. LC-MS/MS analysis and silicon simulation revealed proximity between MetO and Trp residues, facilitating inter- or intra-molecular reactions and ring structure rupture. Remarkably, the presence of γ-T facilitate these phenomena.
Subject(s)
Linseed Oil , Tryptophan , gamma-Tocopherol , Tryptophan/chemistry , Linseed Oil/chemistry , gamma-Tocopherol/chemistry , Oxidation-Reduction , Antioxidants/chemistry , Tandem Mass Spectrometry , Flax/chemistryABSTRACT
ABSTRACT Introduction: Chronic obstructive pulmonary disease (COPD) is one of the most common diseases in the lungs. Objective: To evaluate the clinical effect of respiratory rehabilitation training combined with Traditional Chinese and western medicine on the clinical treatment of motor function in patients with COPD. Methods: 156 patients with chronic obstructive pulmonary disease admitted to a hospital from December 2013 to June 2015 were selected as study subjects and randomly divided into groups for treatment. Results: comparing blood gas exchange rates of patients in the four groups, the experimental group, trained using integrated Chinese and Western medicine, was significantly better than the control groups A, B and C, in aspects such as PaCO2, PaO2, SaO2, pH, etc., the difference was statistically significant (p < 0.05). The improvement of lung function in the experimental group was significantly better than in the other three groups, with statistical significance (p < 0.05). Conclusions: Applying Chinese and Western Medicine combined with comprehensive respiratory rehabilitation training has a significant clinical effect. It effectively improved patients' related clinical indicators and should be widely promoted. Level of evidence II; Therapeutic studies - investigation of treatment results.
RESUMO Introdução: A doença pulmonar obstrutiva crônica (DPOC) é uma das doenças pulmonares mais comuns. Objetivo: Avaliar os efeitos clínicos de treino para reabilitação respiratória somado ao uso de medicina ocidental e medicina tradicional chinesa combinadas, no tratamento da função motora de pacientes com DPOC. Métodos: 156 pacientes com DPOC, hospitalizados entre dezembro de 2013 e junho de 2015, foram selecionados como objetos de estudo e aleatoriamente divididos em grupos de tratamento. Resultados: Quanto aos níveis de troca gasosa dos pacientes nos quatro grupos, o grupo experimental, treinado por meio de práticas de medicina ocidental e de medicina tradicional chinesa combinadas teve uma performance significativamente melhor que a dos grupos A, B, e C, em aspectos tais como PaCO2, PaO2, SaO2, pH, etc., com significância estatística (p<0,05). A melhoria da função pulmonar no grupo experimental também foi significativamente maior que nos outros grupos, mais uma vez com significância estatística (p<0,05). Conclusões: A aplicação da medicina chinesa e da medicina ocidental combinadas, somadas a um treino de reabilitação respiratória abrangente, teve um efeito clínico significativo, efetivamente melhorando indicadores clínicos relevantes. Tal aplicação deveria ser largamente promovida. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.
RESUMEN Introducción: La enfermedad pulmonar obstructiva crónica (EPOC) es una de las enfermedades pulmonares más comunes. Objetivo: Evaluar los efectos clínicos de entrenamiento para rehabilitación respiratoria sumado al uso de medicina occidental y medicina tradicional china combinadas en el tratamiento de la función motora de pacientes con EPOC. Métodos: 156 pacientes con EPOC, hospitalizados entre diciembre de 2013 y junio de 2015, fueron seleccionados como objetos de estudio y aleatoriamente divididos en grupos de tratamiento. Resultados: En cuanto a los niveles de intercambio gaseoso de los pacientes de los cuatro grupos, el grupo experimental, entrenado mediante prácticas combinadas de medicina occidental y medicina tradicional china, obtuvo un rendimiento significativamente mejor que los grupos A, B y C, en aspectos como PaCO2, PaO2, SaO2, pH, etc., con significancia estadística (p<0,05). La mejora de la función pulmonar en el grupo experimental también fue significativamente mayor que en los otros grupos, una vez más con significancia estadística (p<0,05). Conclusiones: La aplicación de la medicina china y de la medicina occidental combinadas, sumadas a un entrenamiento de rehabilitación respiratorio abarcativo, tuvo un efecto clínico significativo, efectivamente mejorando indicadores clínicos relevantes. Tal aplicación debería ser largamente promovida. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.