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We show that a diffusive memristor with analogue switching characteristics can be achieved in a layer of gold nanoparticles (AuNPs) functionalized with charged self-assembled monolayers (deprotonated 11-mercaptoundecanoic acid). The nanoparticle core and the anchored stationary charges are jammed within the layer while the mobile counterions [N(CH3)4+] can respond to the electric field and spontaneously diffuse back to the initial positions upon removal of the field. This metal nanoparticle device is set-step free, energy consumption efficient, mechanically flexible, and analogous to bio-Ca2+ dynamics and has tunable conductance modulation capabilities at the counterion concentrations. The gradual resistive switching behavior enables us to implement several important synaptic functions such as potentiation/depression, spike voltage-dependent plasticity, spike duration-dependent plasticity, spike frequency-dependent plasticity, and paired-pulse facilitation. Finally, on the basis of the paired-pulse facilitation characteristics, the metal nanoparticle diffusive artificial synapse is used for edge extraction with exhibits excellent performance.
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OBJECTIVE: This study aimed to investigate the association between consumption of ultra-processed foods (UPFs) and leucocyte telomere length (LTL). METHODS: This cross-sectional study utilized data from the UK Biobank, including a total of 64,690 participants. LTL was measured using Q-PCR with natural logarithmic conversion and Z-score normalization. Dietary data were collected through a 24-hour recall questionnaire from 2009 to 2010. UPFs were identified using the Nova food classification and analyzed as either a continuous or categorical variable respectively. Multiple linear regression models were employed to analyze the association between UPF consumption and LTL. RESULTS: The included participants had an average age of 56.26 years, of whom 55.2% were female. After adjusting for sociodemographic, lifestyle-related and anthropometric variables, LTL exhibited a decrease of 0.005 (95% CI: -0.007, -0.002) with one UPF serving/day increase. Compared to participants consuming ≤ 3.5 servings/day, those consuming 3.5 to < 6, 6 to ≤ 8 and > 8 servings/day showed a shortening of LTL by 0.025 (95% CI: -0.047, -0.004), 0.034 (95% CI: -0.055, -0.012) and 0.038 (95% CI: -0.062, -0.015), respectively (P for trend = 0.001). Subgroup analyses by UPF subclasses revealed that consumption of ready-to-eat/heated food (ß = -0.008, 95% CI: -0.014, -0.002), beans and potatoes (ß = -0.024, 95% CI: -0.039, -0.009), animal-based products (ß = -0.011, 95% CI: -0.019, -0.004), artificial sugar (ß = -0.014, 95% CI: -0.025, -0.004), and beverages (ß = -0.005, 95% CI: -0.009, -0.001) showed negative associations with LTL. Conversely, breakfast cereals (ß = 0.020, 95% CI: 0.004, 0.036) and vegetarian alternatives (ß = 0.057, 95% CI: 0.027, 0.086) showed positive correlations with LTL. CONCLUSIONS: Our study found that a higher consumption of total UPFs was associated with a shorter LTL. However, some subclass UPFs may be associated with longer LTL, depending on their nutritional composition.
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BACKGROUND: Cadmium toxicity has been associated with disruption of protein homeostasis by interfering with protein folding processes. Heat shock factor 1 (HSF1) coordinates the rapid and extensive cellular response to maintain proteomic balance facing the challenges from many environmental stressors. Thus, we suspect that HSF1 may shield cells from cadmium toxicity by conserving proteome integrity. RESULTS: Here, we demonstrate that cadmium, a highly poisonous metal, induces aggregation of cytosolic proteins in human cells, which disrupts protein homeostasis and activates HSF1. Cadmium exposure increases HSF1's phosphorylation, nuclear translocation and DNA bindings. Aside from this, HSF1 goes through liquid-liquid phase separation to form small nuclear condensates upon cadmium exposure. A specific regulatory domain of HSF1 is critical for HSF1's phase separation capability. Most importantly, human cells with impaired HSF1 are sensitized to cadmium, however, cells with overexpressed HSF1 are protected from cadmium toxicity. Overexpression of HSF1 in human cells reduces protein aggregates, amyloid fibrils and DNA damages to antagonize cadmium toxicity. CONCLUSIONS: HSF1 protects cells from cadmium toxicity by governing the integrity of both proteome and genome. Similar mechanisms may enable HSF1 to alleviate cellular toxicity caused by other heavy metals. HSF1's role in cadmium exposure may provide important insights into the toxic effects of heavy metals on human cells and body organs, allowing us to better manage heavy metal poisoning.
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Cádmio , Proteínas de Ligação a DNA , Humanos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição de Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo , Cádmio/toxicidade , Cádmio/metabolismo , Proteoma/metabolismo , ProteômicaRESUMO
When metal nanoparticles are functionalized with charged ligands, the movement of counterions and conduction electrons is coupled, which enables us to develop electronic devices, including diodes, transistors, and logic gates, but dynamically modulating the conductivity of a synaptic device within these materials has proved challenging. Here we show that an artificial synapse can be created from thin films of functionalized metal nanoparticles using an active silver electrode. The electric-field-injected Ag+ coordinates with carboxyl ligands that sets up a conduction bridge to increase the nanoparticle conductivity by reducing the electron tunneling/hopping energy barriers. The dynamic modulation of conductivity allows us to implement several important synaptic functions such as potentiation/depression, paired-pulse facilitation, learning behaviors including short-term to long-term memory transition, self-learning, and massed leaning vs spaced learning. Finally, based on the nonvolatile characteristics, the metal nanoparticle synapse is used to build a single-layer hardware spiking neural network (SNN) for pattern recognition.
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Nanopartículas Metálicas , Sinapses , Cátions , Eletrônica , LigantesRESUMO
During the SARS-CoV-2 (COVID-19) pandemic, most citizens were cooperative towards the face-masking policy; however, undeniably, face masking has increased complaints of thermal discomfort to varying degrees and resulted in potential health hazards during summer. Thus, a thermal comfort survey was conducted under tree-shaded areas generally preferred by pedestrians to explore the thermal response of face-masked pedestrians. Thirty-two subjects, with and without masks, participated in walking experiments, and their thermal parameters and physiological indicators were recorded; moreover, the subjects were asked to fill in subjective questionnaires. The results showed that although tree shades significantly reduced the average radiant temperature, dampness in the mask may cause some discomfort symptoms, among which intense sweating (54.55%) and tachycardia (42.18%) accounted for the largest proportion. Based on thermal indices, it could be concluded that face-masking does not significantly affect the thermal comfort of subjects walking in shaded areas. Notably, a 30-min walk in tree-shaded areas with face masking does not adversely affect human health or quality of life. Thus, the present assessment of the thermal safety of humans in shaded environments provides reference data for determining thermal comfort levels during outdoor walking with face masking.
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Accurate prediction of the non-uniform contaminant distribution under stratum ventilation (SV) is crucial for optimal design for reducing contaminant exposure risks. Compared with experiments and computational fluid dynamics, zonal models are convenient to implement. This study proposes a zonal model for predicting dynamic non-uniform contaminant distribution in the stratum ventilated room. The zoning method is based on the unique airflow pattern under SV, and the room is divided into the jet zone, entrainment zone, and the mixing zone. The interzonal airflow rate is derived from the profile of the supply air jet. The results show that the proposed zonal model can predict the dynamic contaminant distribution in the stratum ventilated room. Compared with the experimental measurement, the predictions show good accuracy with the mean absolute error (MAE) at 0.51-2.36 ppm and root mean squared error (RMSE) at 0.64-2.53 ppm. The error of the proposed zonal model is influenced by the degree of mixing in each subzone. The proposed zonal model shows better accuracy for non-uniform air distribution under stratum ventilation compared with the existing zonal model.
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Poluição do Ar em Ambientes Fechados , Hidrodinâmica , Ventilação/métodosRESUMO
C3 glomerulopathy is characterized by accumulation of complement C3 within glomeruli. Causes include, but are not limited to, abnormalities in factor H, the major negative regulator of the complement alternative pathway. Factor H-deficient (Cfh-/-) mice develop C3 glomerulopathy together with a reduction in plasma C3 levels. Using this model, we assessed the efficacy of two fusion proteins containing the factor H alternative pathway regulatory domains (FH1-5) linked to either a non-targeting mouse immunoglobulin (IgG-FH1-5) or to an anti-mouse properdin antibody (Anti-P-FH1-5). Both proteins increased plasma C3 and reduced glomerular C3 deposition to an equivalent extent, suggesting that properdin-targeting was not required for FH1-5 to alter C3 activation in either plasma or glomeruli. Following IgG-FH1-5 administration, plasma C3 levels temporally correlated with changes in factor B levels whereas plasma C5 levels correlated with changes in plasma properdin levels. Notably, the increases in plasma C5 and properdin levels persisted for longer than the increases in C3 and factor B. In Cfh-/- mice IgG-FH1-5 reduced kidney injury during accelerated serum nephrotoxic nephritis. Thus, our data demonstrate that IgG-FH1-5 restored circulating alternative pathway activity and reduced glomerular C3 deposition in Cfh-/- mice and that plasma properdin levels are a sensitive marker of C5 convertase activity in factor H deficiency. The immunoglobulin conjugated FH1-5 protein, through its comparatively long plasma half-life, may be a potential therapy for C3 glomerulopathy.
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Complemento C3 , Properdina , Animais , Complemento C3/genética , Convertases de Complemento C3-C5 , Complemento C5 , Fator H do Complemento/genética , Via Alternativa do Complemento , Imunoglobulina G , Camundongos , Properdina/genéticaRESUMO
Eculizumab is a humanized mAb approved for treatment of patients with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Eculizumab binds complement component C5 and prevents its cleavage by C5 convertases, inhibiting release of both the proinflammatory metabolite C5a and formation of the membrane attack complex via C5b. In this study, we present the crystal structure of the complex between C5 and a Fab fragment with the same sequence as eculizumab at a resolution of 4.2 Å. Five CDRs contact the C5 macroglobulin 7 domain, which contains the entire epitope. A complete mutational scan of the 66 CDR residues identified 28 residues as important for the C5-eculizumab interaction, and the structure of the complex offered an explanation for the reduced C5 binding observed for these mutant Abs. Furthermore, the structural observations of the interaction are supported by the reduced ability of a subset of these mutated Abs to inhibit membrane attack complex formation as tested in a hemolysis assay. Our results suggest that eculizumab functions by sterically preventing C5 from binding to convertases and explain the exquisite selectivity of eculizumab for human C5 and how polymorphisms in C5 cause eculizumab-resistance in a small number of patients with paroxysmal nocturnal hemoglobinuria.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Complemento C5/metabolismo , Hemoglobinúria Paroxística/tratamento farmacológico , Fragmentos Fab das Imunoglobulinas/metabolismo , Animais , Ativação do Complemento , Complemento C5/imunologia , Cristalografia por Raios X , Análise Mutacional de DNA , Hemólise , Humanos , Mutação/genética , Filogenia , Ligação Proteica , Conformação Proteica , Relação Estrutura-AtividadeRESUMO
Deep hypothermia or circulation arrest is widely used during total aortic arch replacement. However, conventional procedures have high morbidity and mortality.1 We use the "branch-first" technique2,3 combined with clamping the distal aorta, incorporating a stented elephant trunk to avoid deep hypothermia and circulation arrest. This technique brings us closer to the goal of arch surgery without cerebral or visceral circulatory arrest and the morbidity of deep hypothermia. Early results are encouraging.
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Aorta Torácica/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Parada Circulatória Induzida por Hipotermia Profunda/métodos , Adulto , Idoso , Procedimentos Cirúrgicos Cardíacos/instrumentação , Procedimentos Cirúrgicos Cardíacos/mortalidade , Parada Circulatória Induzida por Hipotermia Profunda/instrumentação , Parada Circulatória Induzida por Hipotermia Profunda/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The link between civilization and technology has long been a hotspot of research around the world. Mobile phone addiction has become a common social phenomenon with advances in society and technology, wreaking havoc on people's emotional health, physical fitness, and personal connections. Considering the positive effects of mindfulness, this study used the diary method to explore the relationship between mindfulness and mobile phone addiction based on the mindfulness reperceiving model. We conducted a 14-day diary study among 198 Chinese youth participants. The results showed that there was a circular argument relationship between mindfulness and mobile phone addiction: mindfulness of the previous day could significantly negatively predict mobile phone addiction of the following day, and vice versa. These results, based on the mindfulness reperceiving model, effectively extend theories and profoundly reveal the circular argument relationship between mindfulness and mobile phone addiction. Besides, it also provides new thought for the mechanism of the interrelationship between mindfulness and mobile phone addiction, as an important theoretical support for the intervention of mobile phone addiction from the perspective of mindfulness.
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Comportamento Aditivo , Telefone Celular , Atenção Plena , Adolescente , Humanos , Atenção Plena/métodos , Comportamento Aditivo/psicologia , Emoções , Dependência de TecnologiaRESUMO
Supercapacitors (SCs), as new energy storage devices with low cost and high performance, urgently require an electrode material with good pore structure and developed graphitization. Herein, we report a 3D hierarchical porous structured carbon aerogel (CA) obtained via dissolving-gelling and a subsequent carbonizing process. The gelling process was realized by using different types of anti-solvents. The carbon aerogel-acetic acid (CA-AA) has a specific surface area of 616.97 m2 g-1 and a specific capacitance of 138 F g-1 which is superior to cellulose-based active carbon. The CA was assembled into a SC, which showed excellent cycle stability. After charging and discharging 5000 times at the current density of 1 A g-1, the capacitance retention ratio of CA-AA reaches 102%. In addition, CA-AA has an energy density of 10.06 W h kg-1 when the power density is 181.06 W kg-1. It provides a choice for non-activation to effectively regulate the porous structure of biomass carbon materials.
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Methanol, serving as a hydrogen carrier, is utilized for hydrogen production through steam reforming, a promising technology for on-vehicle hydrogen applications. Despite the impressive performance of noble-metal catalysts in hydrogen generation, the development of highly efficient non-noble-metal heterogeneous catalysts remains a formidable challenge. In our investigation, we systematically controlled the influence of the MoC phase on the dispersion of active copper metal to enhance the catalytic performance of methanol steam reforming (MSR). Within the Cu/MoC catalyst systems, featuring MoC phases including α-MoC1-x and Mo2C phases, alongside MoO2 phases, the Cu/α-MoC catalyst exhibited exceptional catalytic efficacy at 350 °C. It achieved a remarkable hydrogen selectivity of up to 80% and an outstanding CO selectivity of 0. Notably, its hydrogen production rate reached 44.07 mmol gcat-1 h-1, surpassing that of Cu/Mo2C (37.05 mmol gcat-1 h-1), Cu/MoO2 (19.02 mmol gcat-1 h-1), and commercial CuZnAl (38 mmol gcat-1 h-1) catalysts. Additionally, we introduced the concept of the (Cu1-Cun)/α-MoC catalyst, wherein Cu atoms are immobilized on the α-MoC surface, facilitating the coexistence of isolated Cu atoms (Cu1) and subnanometer copper cluster (Cun) species at a high dispersibility. This innovative design capitalizes on the robust interaction between the α-MoC1-x phase and the Cu active center, yielding a substantial augmentation in the catalytic activity.
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BACKGROUND: The relationships between sleep duration and aging-associated diseases are intricate. Leukocyte telomere length (LTL) is a biomarker of aging, while the association of sleep duration and LTL is unclear. METHODS: The 310,091 study participants from UK Biobank were enrolled in this cross-sectional study. Restricted cubic splines (RCS) analysis was firstly performed to assess the nonlinear relationship between sleep duration and LTL. Sleep duration was then categorized into three groups: <7 h (short sleep duration), 7-8 h (reference group), and >8 h (long sleep duration) and multiple linear regression was applied to analyze the association of short sleep and long sleep duration with LTL. We further performed subgroup analyses stratified by sex, age, chronotype and snoring. RESULTS: RCS showed an inverted J-shaped relationship between sleep duration and LTL. Compared with the reference group, the inverse association of long sleep duration and LTL was statistically significant in fully-adjusted model (P = 0.001). Subgroup analyses showed that this association was more apparent in people over 50 years (51-60 y: P = 0.002; >60 y: P = 0.005), in men (P = 0.022), and in people preferred evening chronotype (P = 0.001). CONCLUSION: Compared with participants sleeping 7-8 h, those sleep longer than 8 h had shorter LTL in middle-aged and young-old adults. The negative association between long sleep duration and LTL was more apparent in older people, in men, and in people preferred evening chronotype.
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Duração do Sono , Biobanco do Reino Unido , Pessoa de Meia-Idade , Adulto , Masculino , Humanos , Idoso , Estudos Transversais , Bancos de Espécimes Biológicos , Leucócitos , TelômeroRESUMO
SCOPE: Alcoholic liver disease (ALD) is a global public health concern. Nobiletin, a polymethoxyflavone abundant in citrus fruits, enhances circadian rhythms and ameliorates diet-induced hepatic steatosis, but its influences on ALD are unknown. This study investigates the role of brain and muscle Arnt-like protein-1 (Bmal1), a key regulator of the circadian clock, in nobiletin-alleviated ALD. METHODS AND RESULTS: This study uses chronic ethanol feeding plus an ethanol binge to establish ALD models in Bmal1flox/flox and Bmal1 liver-specific knockout (Bmal1LKO) mice. Nobiletin mitigates ethanol-induced liver injury (alanine aminotransferase [ALT]), glucose intolerance, hepatic apoptosis, and lipid deposition (triglyceride [TG], total cholesterol [TC]) in Bmal1flox/flox mice. Nobiletin fails to modulated liver injury (ALT, aspartate aminotransferase [AST]), apoptosis, and TG accumulation in Bmal1LKO mice. The expression of lipogenic genes (acetyl-CoA carboxylase alpha [Acaca], fatty acid synthase [Fasn]) and fatty acid oxidative genes (carnitine pamitoyltransferase [Cpt1a], cytochrome P450, family 4, subfamily a, polypeptide 10 [Cyp4a10], and cytochrome P450, family4, subfamily a, polypeptide 14 [Cyp4a14]) is inhibited, and the expression of proapoptotic genes (Bcl2 inteacting mediator of cell death [Bim]) is enhanced by ethanol in Bmal1flox/flox mice. Nobiletin antagonizes the expression of these genes in Bmal1flox/flox mice and not in Bmal1LKO mice. Nobiletin activates protein kinase B (PKB, also known as AKT) phosphorylation, increases the levels of the carbohydrate response element binding protein (ChREBP), ACC1, and FASN, and reduces the level of sterol-regulatory element binding protein 1 (SREBP1) and phosphorylation of ACC1 in a Bmal1-dependent manner. CONCLUSION: Nobiletin alleviates ALD by increasing the expression of genes involved in fatty acid oxidation by increasing AKT phosphorylation and lipogenesis in a Bmal1-dependent manner.
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Fatores de Transcrição ARNTL , Flavonas , Lipogênese , Hepatopatias Alcoólicas , Camundongos Knockout , Proteínas Proto-Oncogênicas c-akt , Animais , Flavonas/farmacologia , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Hepatopatias Alcoólicas/prevenção & controle , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Lipogênese/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Masculino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Camundongos , Substâncias Protetoras/farmacologia , Etanol , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacosRESUMO
The bispecific antibody gefurulimab (also known as ALXN1720) was developed to provide patients with a subcutaneous treatment option for chronic disorders involving activation of the terminal complement pathway. Gefurulimab blocks the enzymatic cleavage of complement component 5 (C5) into the biologically active C5a and C5b fragments, which triggers activation of the terminal complement cascade. Heavy-chain variable region antigen-binding fragment (VHH) antibodies targeting C5 and human serum albumin (HSA) were isolated from llama immune-based libraries and humanized. Gefurulimab comprises an N-terminal albumin-binding VHH connected to a C-terminal C5-binding VHH via a flexible linker. The purified bispecific VHH antibody has the expected exact size by mass spectrometry and can be formulated at greater than 100 mg/mL. Gefurulimab binds tightly to human C5 and HSA with dissociation rate constants at pH 7.4 of 54 pM and 0.9 nM, respectively, and cross-reacts with C5 and serum albumin from cynomolgus monkeys. Gefurulimab can associate with C5 and albumin simultaneously, and potently inhibits the terminal complement activity from human serum initiated by any of the three complement pathways in Wieslab assays. Electron microscopy and X-ray crystallography revealed that the isolated C5-binding VHH recognizes the macroglobulin (MG) 4 and MG5 domains of the antigen and thereby is suggested to sterically prevent C5 binding to its activating convertase. Gefurulimab also inhibits complement activity supported by the rare C5 allelic variant featuring an R885H substitution in the MG7 domain. Taken together, these data suggest that gefurulimab may be a promising candidate for the potential treatment of complement-mediated disorders.
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Complemento C5 , Anticorpos de Domínio Único , Humanos , Proteínas do Sistema Complemento/metabolismo , Ativação do Complemento , AlbuminasRESUMO
OBJECTIVE: To evaluate the novel method of combinedly use of occluder and bare stent in the treatment of aortic dissection with distal tear at visceral branches. METHODS: From April 2010 to September 2012, 6 patients (5 male and 1 female patients, aged from 29 to 62 years, mean 47.2 years) were diagnosed as Stanford type B aortic dissection that been revealed by CT angiography. The main tears were sealed with stent-grafts firstly, and then the tears at the visceral branch area were evaluated that impossible to close spontaneously. Atrium septal defect occluder and ventricular septal defect were implanted at the tears with the anterior disc in false lumen, while the posterior disc in the true lumen. After that, the bare stents were implanted in the true lumen to pull the occluders on the aortic wall. RESULTS: Among the 6 procedures, occluders were successfully implanted in 5 cases, and 1 failed anchoring at the tear, and the alternative method of coils embolization was applicated. After all the procedures, the immediate aortogrophy revealed that the false lumen disappeared in the 5 cases that occluders were used, and the visceral branches were all patent. No paraplegia, lesion of visceral organs or other complications occurred. All the cases were followed at least 5 months. There was one endoleak due to a non-sealed tear at the descending aorta, one new-occurred small tear in the descending aorta but with no communication to the false lumen. CONCLUSIONS: The combinedly use of occluder and bare stent in the treatment of aortic dissection with tears at the visceral branch area is a sum of two simple technique plus each other. It is easily to master. The lesions at the aortic that ordinary stent-grafting incapable to seal are successfully solved then. The huge trauma of open or hybrid procedures are avoided.
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Dissecção Aórtica , Implante de Prótese Vascular , Dissecção Aórtica/cirurgia , Aneurisma Aórtico/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Humanos , StentsRESUMO
Sensing and computing are two important ways in which humans attempt to perceive and understand the analog world through digital devices. Analog-to-digital converters (ADCs) discretize analog signals while the data bus transmits digital data between the components of a computer. With the increase in sensor nodes and the application of deep neural networks, the energy and time consumption limit the increment of data throughput. In-sensor computing is a computing paradigm that integrates sensing, storage, and processing in one device without ADCs and data transfer. According to the integration degree, herein, we summarize four levels of in-sensor computing in the field of artificial olfactory. In the first level, we show that different functions are conducted by using discrete components. Next, the data conversion and transfer are exempt within the in-memory computing architecture with necessary data encoding. Subsequently, in-sensor computing is integrated into a single device. Finally, multi-modal in-sensor computing is proposed to improve the quality and reliability of the classification results. At the end of this minireview, we provide an outlook on the use of metal nanoparticle devices to achieve such in-sensor computing for bionic olfaction.
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This study sought to understand the nature of the immune complexes that could be formed when a patient is exposed simultaneously to two different anti-complement component 5 (C5) antibodies, such as in patients converting from one bivalent, noncompetitive, C5-binding monoclonal antibody to another. Size exclusion chromatography (SEC) in combination with multiangle light scattering was used to assess the potential formation of multivalent complexes among eculizumab, C5, and each of two other anti-C5 bivalent antibodies, TPP-2799 or TP-3544, respectively having the same sequence as either crovalimab or pozelimab currently undergoing clinical trials. Each of these two antibodies bound C5 noncompetitively with eculizumab. In phosphate-buffered saline (PBS), C5-eculizumab in the absence of other antibodies measured <500 kDa; however, inclusion of other antibodies at levels ranging from equimolar and up to a fivefold excess over eculizumab and C5 yielded a series of complexes with some >1500 kDa in size, consistent with incorporation of multiple antibodies and C5 molecules. A similar pattern of complexes was also observed when fluorescently labeled eculizumab and either of the other two antibodies were spiked into human plasma, based on SEC monitored by fluorescence detection. A detailed characterization of the pharmacodynamic and pharmacokinetic properties of such complexes is warranted, as is the incorporation of mitigation processes to avoid their formation in patients converting from one bivalent, noncompetitive, C5-binding monoclonal antibody to another.
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Complemento C5 , Hemoglobinúria Paroxística , Humanos , Ativação do Complemento , Hemoglobinúria Paroxística/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Complexo Antígeno-AnticorpoRESUMO
Wood has a rich three-dimensional pore structure and many bottom-up nanochannels. However, the structure of wood itself has limited ability to adsorb dyes, so the effective combination of the unique structure of wood and Pd NPs was studied to achieve efficient degradation of dyes. First, the three-dimensional structure of natural wood is optimized by combining the complex pore structure of wood with Pd NPs to improve the contact process between the dye and Pd NPs. Then, Pd (II) ion can be well reduced to Pd NPs by wood lignin. In addition, Pd NPs can be fixed by hydroxyl groups on cellulose in wood. The flow state inside Pd NPs/wood film and the contact area between catalyst and dye were discussed in detail by hydrodynamic simulation, which filled the gap. It provides reference for composite structure. When Pd NPs/wood membrane was used to treat methylene blue (MB), the degradation efficiency was up to 96.7%, which was 90% higher than that of natural wood. Its TOF value was 1.82 molMB molPd-1min-1, which was higher than that in the previous literature. Therefore, the novelty of this study is that the mechanism of catalytic degradation of MB by Pd nanoparticles/wood composites is reported for the first time. The internal flow mode and contact condition of the new material are understood, which has a good application prospect.
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Nanopartículas Metálicas , Azul de Metileno , Azul de Metileno/química , Madeira , Corantes/química , Lignina , Nanopartículas Metálicas/químicaRESUMO
Shrinking the size of the electronic synapse to molecular length-scale, for example, an artificial synapse directly fabricated by using individual or monolayer molecules, is important for maximizing the integration density, reducing the energy consumption, and enabling functionalities not easily achieved by other synaptic materials. Here, we show that the conductance of the self-assembled peptide molecule monolayer could be dynamically modulated by placing electrical biases, enabling us to implement basic synaptic functions. Both short-term plasticity (e.g., paired-pulse facilitation) and long-term plasticity (e.g., spike-timing-dependent plasticity) are demonstrated in a single molecular synapse. The dynamic current response is due to a combination of both chemical gating and coordination effects between Ag+ and hosting groups within peptides which adjusts the electron hopping rate through the molecular junction. In the end, based on the nonlinearity and short-term synaptic characteristics, the molecular synapses are utilized as reservoirs for waveform recognition with 100% accuracy at a small mask length.