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Achieving high-performance materials with superior mechanical properties and electrical conductivity, especially in large-sized bulk forms, has always been the goal. However, it remains a grand challenge due to the inherent trade-off between these properties. Herein, by employing nanodiamonds as precursors, centimeter-sized diamond/graphene composites were synthesized under moderate pressure and temperature conditions (12 GPa and 1,300 to 1,500 °C), and the composites consisted of ultrafine diamond grains and few-layer graphene domains interconnected through covalently bonded interfaces. The composites exhibit a remarkable electrical conductivity of 2.0 × 104 S m-1 at room temperature, a Vickers hardness of up to ~55.8 GPa, and a toughness of 10.8 to 19.8 MPa m1/2. Theoretical calculations indicate that the transformation energy barrier for the graphitization of diamond surface is lower than that for diamond growth directly from conventional sp2 carbon materials, allowing the synthesis of such diamond composites under mild conditions. The above results pave the way for realizing large-sized diamond-based materials with ultrahigh electrical conductivity and superior mechanical properties simultaneously under moderate synthesis conditions, which will facilitate their large-scale applications in a variety of fields.
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Conventional solid-based SERS substrates often face challenges with inconsistent sample distribution, while liquid-based SERS substrates are prone to aggregation and precipitation, resulting in irreproducible signals in both cases. In this study, we tackled this dilemma by designing and synthesizing raspberry-like plasmonic nanoaggregates that exhibit a high density of hotspots and are colloidally stable at the same time. In particular, the nanoaggregates consist of a core made of functionalized polystyrene (PS) microspheres, which act as a template for rapid self-assembly of Au@Ag core-shell nanoparticles to form raspberry-like hierarchical nanoaggregates within 5 min of mixing. The optimized nanoaggregates can be used as reproducible and stable SERS substrates for a range of wastewater pollutants (e.g., rhodamine 6G (R6G) and malachite green (MG)) and nucleobases (e.g., adenine and uracil), with the detection limits as low as 1 × 10-10, 1 × 10-16, 3 × 10-8, and 3 × 10-7 M, respectively. Additionally, the trace detection of adenine in clinical urine samples has been successfully demonstrated. Our modular assembly approach opens up new possibilities in SERS substrate design and advanced trace-chemical detection technologies.
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Intra-individual response time variability (IIRTV) during cognitive performance is increasingly recognized as an important indicator of attentional control (AC) and related brain region function. However, what determinants contribute to preschoolers' IIRTV received little attention. The present study explored the interaction of dopaminergic polygenic composite score (DPCS) and the parent-child relationship in relation to preschoolers' IIRTV. In the initial sample, 452 preschoolers (M age = 5.17, SD = 0.92) participated in the study. The modified Flanker task was used to evaluate children's IIRTV and their parents were requested to complete the Parent-Child Relationship Scale to assess the parent-child relationship (closeness/conflict). DNA data were extracted from children's saliva samples, and a DPCS was created by the number of COMT, DAT1, and DRD2 alleles associated with lower dopamine levels. Results showed that DPCS significantly interacted with the parent-child closeness to impact preschoolers' IIRTV. Specifically, preschoolers with higher DPCS exhibited lower IIRTV under higher levels of the parent-child closeness, and greater IIRTV under lower levels of the parent-child closeness compared to those with lower DPCS, which supported the differential susceptibility theory (DST). A direct replication attempt with 280 preschoolers (M age = 4.80, SD = 0.86) was conducted to investigate whether the results were in accordance with our exploratory outcomes. The interactive effect of DPCS and the parent-child closeness on IIRTV was confirmed. Additionally, the significant interactive effect of DPCS and the parent-child conflict on IIRTV was found in the replication study. The findings indicate that preschoolers' IIRTV, as an indicator of AC and related brain region function, is influenced by the interactions of dopaminergic genotypes and the parent-child relationship. RESEARCH HIGHLIGHTS: We investigated the Gene × Environment mechanism to underline the intra-individual response time variability as an indicator of attentional control (AC) in Chinese preschoolers. Dopaminergic polygenic composite score (COMT, DAT1, and DRD2) interacted with the parent-child relationship to predict preschoolers' intra-individual reaction time variability. A direct replication attempt has been conducted, and the results were in accordance with our exploratory outcomes, which increased the credibility of the present findings. The findings highlight the importance of considering precursors, including polygenic and environmental factors, which contribute to the development of early cognitive performance such as AC.
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Catecol O-Metiltransferase , Genótipo , Relações Pais-Filho , Tempo de Reação , Receptores de Dopamina D2 , Humanos , Pré-Escolar , Feminino , Masculino , Catecol O-Metiltransferase/genética , Receptores de Dopamina D2/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Dopamina/metabolismo , Atenção/fisiologia , Cognição/fisiologiaRESUMO
The extensive use of mineral fertilizers has a negative impact on the environment, whereas wastewater and microalgal biomass can provide crops with nutrients such as nitrogen, phosphorus, and potassium, and have the potential to be used as a source of fertilizers in circular agriculture. In this study, a step-by-step resource utilization study of algae-containing wastewater generated from microalgae treatment of swine wastewater was carried out. When wheat seedlings were cultivated in the effluent after microalgae separation, the root fresh weight, seedling fresh weight, and total seedling length were increased by 3.44%, 14.45%, and 13.64%, respectively, compared with that of the algae-containing wastewater, and there was no significant difference in seedling fresh weight, total seedling length, maximum quantum yields of PSII photochemistry (Fv/Fm), and performance index (PIABS) from that of the Hogland solution group, which has the potential to be an alternative liquid fertilizer. Under salt stress, microalgae extract increased the contents of GA3, IAA, ABA, and SA in wheat seedlings, antioxidant enzymes maintained high activity, and the PIABS value increased. Low-dose microalgae extract (1 mL/L) increased the root fresh weight, seedling fresh weight, longest seedling length, and total seedling length by 30.73%, 31.28%, 16.43%, and 28.85%, respectively. Algae extract can act as a plant biostimulant to regulate phytohormone levels to attenuate the damage of salt stress and promote growth.
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Biomassa , Microalgas , Plântula , Triticum , Águas Residuárias , Triticum/crescimento & desenvolvimento , Triticum/efeitos dos fármacos , Microalgas/crescimento & desenvolvimento , Microalgas/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/efeitos dos fármacos , Animais , Águas Residuárias/química , Suínos , Tolerância ao Sal , Fertilizantes/análise , Eliminação de Resíduos Líquidos/métodosRESUMO
BACKGROUND: Surgery in geriatric patients often poses risk of major postoperative complications. Acute kidney injury (AKI) is a common complication following noncardiac surgery and is associated with increased mortality. Early identification of geriatric patients at high risk of AKI could facilitate preventive measures and improve patient prognosis. This study used machine learning methods to identify important features and predict AKI following noncardiac surgery in geriatric patients. METHODS: The data for this study were obtained from a prospective cohort. Patients aged ≥ 65 years who received noncardiac surgery from June 2019 to December 2021 were enrolled. Data were split into training set (from June 2019 to March 2021) and internal validation set (from April 2021 to December 2021) by time. The least absolute shrinkage and selection operator (LASSO) regularization algorithm and the random forest recursive feature elimination algorithm (RF-RFE) were used to screen important predictors. Models were trained through extreme gradient boosting (XGBoost), random forest, and LASSO. The SHapley Additive exPlanations (SHAP) package was used to interpret the machine learning model. RESULTS: The training set included 6753 geriatric patients. Of these, 250 (3.70%) patients developed AKI. The XGBoost model with RF-RFE selected features outperformed other models with an area under the precision-recall curve (AUPRC) of 0.505 (95% confidence interval [CI]: 0.369-0.626) and an area under the receiver operating characteristic curve (AUROC) of 0.806 (95%CI: 0.733-0.875). The model incorporated ten predictors, including operation site and hypertension. The internal validation set included 3808 geriatric patients, and 96 (2.52%) patients developed AKI. The model maintained good predictive performance with an AUPRC of 0.431 (95%CI: 0.331-0.524) and an AUROC of 0.845 (95%CI: 0.796-0.888) in the internal validation. CONCLUSIONS: This study developed a simple machine learning model and a web calculator for predicting AKI following noncardiac surgery in geriatric patients. This model may be a valuable tool for guiding preventive measures and improving patient prognosis. TRIAL REGISTRATION: The protocol of this study was approved by the Committee of Ethics from West China Hospital of Sichuan University (2019-473) with a waiver of informed consent and registered at www.chictr.org.cn (ChiCTR1900025160, 15/08/2019).
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Injúria Renal Aguda , Aprendizado de Máquina , Complicações Pós-Operatórias , Humanos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/epidemiologia , Idoso , Feminino , Masculino , Estudos Prospectivos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Idoso de 80 Anos ou mais , Medição de Risco/métodos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Fatores de RiscoRESUMO
BACKGROUND: The integration of telehealth-supported programs in chronic disease management has become increasingly common. However, its effectiveness for individuals with knee osteoarthritis (KOA) remains unclear. OBJECTIVE: This study aimed to assess the effectiveness of telehealth-supported exercise or physical activity programs for individuals with KOA. METHODS: A comprehensive literature search encompassing Embase, MEDLINE, CENTRAL, Web of Science, PubMed, Scopus, PEDro, GreyNet, and medRxiv from inception to September 2023 was conducted to identify randomized controlled trials comparing telehealth-supported exercise or physical activity programs to a control condition for KOA. Data were extracted and qualitatively synthesized across eligible studies, and a meta-analysis was performed to evaluate the effects. The study was reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020. RESULTS: In total, 23 studies met eligibility criteria, with 20 included in the meta-analysis. Results showed that telehealth-supported exercise or physical activity programs reduced pain (g=-0.39; 95% CI -0.67 to -0.11; P<.001), improved physical activity (g=0.13; 95% CI 0.03-0.23; P=.01), and enhanced physical function (g=-0.51; 95% CI -0.98 to -0.05; P=.03). Moreover, significant improvements in quality of life (g=0.25; 95% CI 0.14-0.36; P<.001), self-efficacy for pain (g=0.72; 95% CI 0.53-0.91; P<.001), and global improvement (odds ratio 2.69, 95% CI 1.41-5.15; P<.001) were observed. However, self-efficacy for physical function (g=0.14; 95% CI -0.26 to 0.53; P=.50) showed insignificant improvements. Subgroup analyses based on the World Health Organization classification of digital health (pain: χ22=6.5; P=.04 and physical function: χ22=6.4; P=.04), the type of teletechnology in the intervention group (pain: χ24=4.8; P=.31 and function: χ24=13.0; P=.01), and active or inactive controls (pain: χ21=5.3; P=.02 and physical function: χ21=3.4; P=.07) showed significant subgroup differences. CONCLUSIONS: Telehealth-supported exercise or physical activity programs might reduce knee pain and improve physical activity, physical function, quality of life, self-efficacy, and global improvement in individuals with KOA. Future research should consider longer implementation durations and assess the feasibility of incorporating wearables and standardized components into large-scale interventions to evaluate the effects. TRIAL REGISTRATION: PROSPERO CRD42022359658; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=359658.
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Terapia por Exercício , Exercício Físico , Osteoartrite do Joelho , Telemedicina , Humanos , Osteoartrite do Joelho/reabilitação , Osteoartrite do Joelho/terapia , Terapia por Exercício/métodos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Feminino , Masculino , Pessoa de Meia-IdadeRESUMO
T cell-based adoptive cell therapy (ACT) has exhibited excellent antitumoral efficacy exemplified by the clinical breakthrough of chimeric antigen receptor therapy (CAR-T) in hematologic malignancies. It relies on the pool of functional T cells to retain the developmental potential to serially kill targeted cells. However, failure in the continuous supply and persistence of functional T cells has been recognized as a critical barrier to sustainable responses. Conferring stemness on infused T cells, yielding stem cell-like memory T cells (TSCM) characterized by constant self-renewal and multilineage differentiation similar to pluripotent stem cells, is indeed necessary and promising for enhancing T cell function and sustaining antitumor immunity. Therefore, it is crucial to identify TSCM cell induction regulators and acquire more TSCM cells as resource cells during production and after infusion to improve antitumoral efficacy. Recently, four common cytokine receptor γ chain (γc) family cytokines, encompassing interleukin-2 (IL-2), IL-7, IL-15, and IL-21, have been widely used in the development of long-lived adoptively transferred TSCM in vitro. However, challenges, including their non-specific toxicities and off-target effects, have led to substantial efforts for the development of engineered versions to unleash their full potential in the induction and maintenance of T cell stemness in ACT. In this review, we summarize the roles of the four γc family cytokines in the orchestration of adoptively transferred T cell stemness, introduce their engineered versions that modulate TSCM cell formation and demonstrate the potential of their various combinations. Video Abstract.
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Linfócitos T CD8-Positivos , Citocinas , Imunoterapia Adotiva , Células-Tronco , Transdução de SinaisRESUMO
As an important phase-change material, GeTe has many high-pressure phases as well, but its phase transitions under pressure are still lack of clarity. It is challenging to identify high-pressure GeTe crystal structures owing to the phase coexistence in a wide pressure range and the reversibility of phase transitions. Hence, first-principles calculations are required to provide further information in addition to limited experimental characterizations. In this work, a new orthorhombic Cmca GeTe high-pressure phase has been predicted via the CALYPSO method as the most energetically favorable phase in the pressure range between â¼30 and â¼38.5 GPa, which would update the GeTe high-pressure phase transition sequence. The crystal structure of the Cmca phase is composed of alternate stacking puckered layers of Ge six-membered rings and Te four-membered rings along the b direction. The high density of states near the Fermi level and delocalization of electrons from the two-dimensional electron localization function indicate a strong metallic property of the Cmca phase. Electron-phonon coupling calculations indicate that the Cmca phase is superconductive below â¼4.2 K at 35 GPa. The simulated x-ray diffraction pattern of the Cmca phase implies that this phase might coexist with the Pnma-boat phase under high pressure. These results offer further understanding on the high-pressure structural evolution and physical properties in GeTe and other IV-VI semiconductors.
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In recent years, skutterudite filled with electronegative elements (S, Se, Cl, Br) has attracted the extensive attention of researchers. By doping electron donors (Pb, Ni, or Te, S, Se) at the Co or Sb sites, the electronegative elements can form thermodynamically stable compounds in the intrinsic pores of the skutterudite, substantially expanding the research scope of skutterudite. In this study, S0.05Co4Sb11.3Te0.6Se0.1 skutterudite was synthesized at high pressure and high temperature, with a pressure range of 2.0-3.5 GPa. The phase composition, micro-morphology, and electrical and thermal transport properties were systematically characterized. The micromorphology analysis shows that the introduction of S element and substituting Te and Se at the Sb sites inhibit the grain growth in a suitable high-pressure environment. Substantial differences are observed in the directions of the lattice stripes in the samples, and rich grain boundaries and many lattice distortions and dislocation defects occur. The carrier concentration can be optimized by filling the voids of the skutterudite with a few S atoms, and the thermoelectric properties can be optimized by scattering phonons through resonance scattering and defect scattering. The samples synthesized at a pressure of 3.0 GPa and a temperature of 900 K have a maximum power factor of 23.85 × 10-4 W m-1 K-2 and a maximum zT value of 1.30 at a test temperature of 773 K.
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OBJECTIVES: Autonomic nervous activity imbalance plays an important role in atrial fibrillation (AF). AF can be treated by acupuncture at the Neiguan point (PC6), but the mechanism remains elusive. Here, we investigated autonomic nervous system activity in electroacupuncture (EA) at PC6 in a rat AF model. MATERIAL AND METHODS: In this study, we established a rat AF model via tail vein injection with ACh-CaCl2 for ten consecutive days with or without EA at PC6. AF inducibility and heart rate variability (HRV) were assessed by electrocardiogram. Next, we completed in vivo recording of the activity of cervical sympathetic and vagal nerves, respectively. Finally, the activities of brain regions related to autonomic nerve regulation were assessed by c-Fos immunofluorescence and multichannel recording. RESULTS: EA at PC6 decreased AF inducibility and prevented changes in HRV caused by ACh-CaCl2 injection. Meanwhile, EA at PC6 reversed the increased sympathetic and decreased vagal nerve activity in AF rats. Furthermore, EA treatment downregulated increased c-Fos expression in brain regions, including paraventricular nucleus, rostral ventrolateral medulla, and dorsal motor nucleus of the vagus in AF, while c-Fos expression in nucleus ambiguus was upregulated with EA. CONCLUSION: The protective effect of EA at PC6 on AF is associated with balance between sympathetic and vagal nerve activities.
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Trial-to-trial intraindividual reaction time variability (IIRTV) serves as an index of attentional control and related endogenous brain function. What determinants contribute to preschoolers' attentional control indexed by IIRTV remains unknown. The present study examined how catechol-o-methyltransferase (COMT) rs4680 polymorphism interacted with family functioning (cohesion and adaptability) to impact on preschoolers' attentional control indexed by IIRTV. One hundred forty-four preschool children (Mage = 4.19, SD = 0.63) completed the flanker task to assess their IIRTV. Their parents were asked to fill out the Family Adaptability and Cohesion Evaluation Scale II to assess family functioning. After controlling for age, socioeconomic status (SES) and mean reaction time, results showed that the COMT rs4680 polymorphism was positively associated with preschoolers' IIRTV at the 5% significance level (p = .02) but not after multiple testing adjustment (p = .08). Moreover the COMT rs4680 polymorphism significantly interacted with family functioning to impact on preschoolers' IIRTV and the interaction effects remained significant after correction for multiple testing (p = .01, ΔR2 = 0.06 in congruent conditions; p = .04, ΔR2 = 0.04 in combined conditions). In addition, the significant interaction between SES and COMT rs4680 polymorphism was also found in the present study (p = .01, ΔR2 = 0.05 in congruent conditions; p = .05, ΔR2 = 0.03 in combined conditions). No sex differences were found in the present sample. The findings of the present study expand our knowledge about the gene × environment underpinnings of children's attentional control and endogenous brain function, and provide evidence for the Vantage Sensitivity model on children's development.
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Atenção , Catecol O-Metiltransferase , Catecol O-Metiltransferase/genética , Pré-Escolar , Genótipo , Humanos , Pais , Polimorfismo de Nucleotídeo Único , Tempo de ReaçãoRESUMO
In the original article.
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Pectinase is widely used in numerous industrial fields, including the food, wine, and paper industries. In this work, seven bacteria were isolated from orange peel and their pectinase production activity was assayed. One bacterium (OR-B2) identified as a Bacillus sp. showed the highest enzyme activity towards others. A gene encoding a pectate lyase designed as PelB-B2 in this work was amplified and heterogeneous expressed in E.coli. PelB-B2 was defined as a member of the PelB pectate lyase family after phylogenic tree analysis. 3D model of PelB-B2 was constructed by SWISS-MODEL and PelB-B2 showed conserved para-ß structure. After inducing culture and purified by Ni-affinity chromatography, the properties of the purified PelB-B2 were assayed. Optimal pH and temperature for PelB-B2 was pH 8.0 and 50 °C, respectively. PelB-B2 showed excellent pH stability and thermostability. It was stable within pH range 3.0-11.0 and retained more than 51% activity after incubation at 40 °C, 50 °C, or 60 °C for 1 h. Furthermore, we determined that PelB-B2 was a Ca2+-dependent pectinase and the pectin extracted from citrus was the benefit substrate for PelB-B2. The Km and Vmax of PelB-B2 were 1.64 g/L and 232.56 mol/(L min), respectively. The OR-B2 can be a new resource for pectinase production and the PelB-B2 has potential for industrial application. 7 bacteria were isolated from orange peel, namely OR-B1 to OR-B7 and their pectinase activities were assayed. One pectate lyase belongs to PelB family was cloned from OR-B2 and heterogeneous expressed in E. coli. Purified PelB-B2 was further studied with its properties. Effects of pH, temperature, chemicals, substrate on the enzyme activity were assayed and the enzyme kinetic was also measured.
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Bacillus/enzimologia , Pectinas/metabolismo , Poligalacturonase/metabolismo , Bacillus/genética , Bacillus/metabolismo , Citrus/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Concentração de Íons de Hidrogênio , Cinética , Poligalacturonase/biossíntese , Polissacarídeo-Liases/metabolismo , TemperaturaRESUMO
This study developed a nano-magnetite-modified biochar material (m-biochar) using a simple and rapid in situ synthesis method via microwave treatment, and systematically investigated the removal capability and mechanism of chromium (VI) by this m-biochar from contaminated groundwater. The m-biochar was fabricated from reed residues and magnetically modified by nano-Fe3O4. The results from scanning electron microscopy (SEM) and X-ray diffraction (XRD) characterisations confirmed the successful doping of nano-Fe3O4 on the biochar with an improved porous structure. The synthesised m-biochar exhibited significantly higher maximum adsorption capacity of 9.92 mg/g compared with that (8.03 mg/g) of the pristine biochar. The adsorption kinetics followed the pseudo-second-order model and the intraparticle diffusion model, which indicated that the overall adsorption rate of Cr(VI) was governed by the processes of chemical adsorption, liquid film diffusion and intramolecular diffusion. The increasing of the pH from 3 to 11 significantly affected the Cr(VI) adsorption, where the capabilities decreased from 9.92 mg/g to 0.435 mg/g and 8.03 mg/g to 0.095 mg/g for the m-biochar and pristine biochar, respectively. Moreover, the adsorption mechanisms of Cr(VI) by m-biochar were evaluated and confirmed to include the pathways of electrostatic adsorption, reduction and complexation. This study highlighted an effective synthesis method to prepare a superior Cr(VI) adsorbent, which could contribute to the effective remediation of heavy metal contaminations in the groundwater.
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Carvão Vegetal/química , Cromo/química , Óxido Ferroso-Férrico/química , Água Subterrânea/química , Poluentes Químicos da Água/química , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Magnetismo/métodos , Micro-Ondas , NanopartículasRESUMO
Optical detection has become a convenient and scalable approach to read out information from microfluidic systems. For the study of many key biomolecules, however, including peptides and proteins, which have low fluorescence emission efficiencies at visible wavelengths, this approach typically requires labeling of the species of interest with extrinsic fluorophores to enhance the optical signal obtained - a process which can be time-consuming, requires purification steps, and has the propensity to perturb the behavior of the systems under study due to interactions between the labels and the analyte molecules. As such, the exploitation of the intrinsic fluorescence of protein molecules in the UV range of the electromagnetic spectrum is an attractive path to allow the study of unlabeled proteins. However, direct visualization using 280 nm excitation in microfluidic devices has to date commonly required the use of coherent sources with frequency multipliers and devices fabricated out of materials that are incompatible with soft lithography techniques. Here, we have developed a simple, robust, and cost-effective 280 nm LED platform that allows real-time visualization of intrinsic fluorescence from both unlabeled proteins and protein complexes in polydimethylsiloxane microfluidic channels fabricated through soft lithography. Using this platform, we demonstrate intrinsic fluorescence visualization of proteins at nanomolar concentrations on chip and combine visualization with micron-scale diffusional sizing to measure the hydrodynamic radii of individual proteins and protein complexes under their native conditions in solution in a label-free manner.
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Técnicas Analíticas Microfluídicas/instrumentação , Proteínas/análise , Animais , Bovinos , Galinhas , Difusão , Dimetilpolisiloxanos/química , Desenho de Equipamento , Fluorescência , Hidrodinâmica , Dispositivos Lab-On-A-Chip , Muramidase/análise , Soroalbumina Bovina/análise , Soluções , Cadeia B de alfa-Cristalina/análiseRESUMO
We developed suitable high-pressure and high-temperature (HPHT) conditions for improvement of the thermoelectric properties of nonstoichiometric TiO1.80. X-ray diffraction, scanning transmission microscopy, transmission electron microscopy, and ultraviolet spectral measurements demonstrate that the crystal structures and microstructures are strongly modulated by our HPHT. The electrical properties and thermal conductivity are improved simultaneously by raising the reactive sintering pressure. The band gap was narrowed, contributing to the increase of the electrical properties with the pressure. In addition, relatively low thermal conductivities were obtained here as a result of a full spectrum of phonon scattering, benefiting from our deliberately engineered microstructures via HPHT. As a consequence, a high dimensionless figure of merit (zT) of 0.36 was obtained at 700 °C in the sample fabricated at 5 GPa. As far as we know, this is higher than all of the results of nonstoichiometric titanium oxide by other means and an enhancement of 57% of the best ever result. HPHT offers us a promising alternative for optimization of the thermoelectric properties, and it is worthwhile to popularize it.
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Alzheimer's disease (AD) is complex and multifactorial, and its pathogenesis involves multiple factors and processes. This study pioneered the in situ growth of cerium oxide nanoparticles on macrophage membranes (Ce-RAW). Further, carbon quantum dots (CQD) were biomimetically modified by Ce-RAW, leading to the synthesis of a multifunctional nanocomposite (CQD-Ce-RAW). Within the framework of this research, CQD-Ce-RAW was strategically combined with photothermal therapy (PTT), aiming to achieve a more significant therapeutic effect. The macrophage membrane confers the system with anti-phagocytic and anti-inflammatory biological functions. More importantly, the ultra-small size of cerium oxide grown on the membrane acts as a reactive oxygen species (ROS) scavenger and alleviates the degree of oxidative stress. Meanwhile, CQD as a photosensitizer helps dissociate amyloid-ß (Aß) aggregates and chelates excess copper ions, thus further inhibiting Aß aggregation. Cell experiments showed that CQD-Ce-RAW combined with PTT could effectively degrade and inhibit the aggregation of Aß, remove ROS, and improve cell survival rate. The results of in vivo photothermal experiments demonstrated that near-infrared light enhanced the efficiency of drug penetration through the blood-brain barrier and facilitated its accumulation in brain tissue. This comprehensive therapeutic approach can intervene in the disease progression from multiple pathways, providing a new prospect for treating AD.
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Doença de Alzheimer , Biofilmes , Cério , Nanopartículas , Terapia Fototérmica , Espécies Reativas de Oxigênio , Cério/química , Cério/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/terapia , Doença de Alzheimer/patologia , Animais , Camundongos , Nanopartículas/química , Biofilmes/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Pontos Quânticos/química , Peptídeos beta-Amiloides/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Tamanho da Partícula , Células RAW 264.7 , Humanos , Propriedades de Superfície , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacosRESUMO
Circular RNAs (circRNAs) constitute a class of endogenous non-coding RNAs (ncRNAs) that lack a 5'-ended cap and 3'-ended poly (A) tail and form a closed ring structure with covalent bonds. Due to its special structure, circRNA is resistant to Exonuclease R (RNaseR), making its distribution in the cytoplasm quite rich. Advanced high-throughput sequencing and bioinformatics methods have revealed that circRNA is highly conserved, stable, and disease- and tissue-specific. Furthermore, increasing research has confirmed that circRNA, as a driver or suppressor, regulates cancer onset and progression by modulating a series of pathophysiological mechanisms. As a result, circRNA has emerged as a clinical biomarker and therapeutic intervention target. This article reviews the biological functions and regulatory mechanisms of circRNA in the context of respiratory cancer onset and progression.
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Alzheimer's disease (AD) has a complex etiology and diverse pathological processes. The therapeutic effect of single-target drugs is limited, so simultaneous intervention of multiple targets is gradually becoming a new research trend. Critical stages in AD progression involve amyloid-ß (Aß) self-aggregation, metal-ion-triggered fibril formation, and elevated reactive oxygen species (ROS). Herein, red blood cell membranes (RBC) are used as templates for the in situ growth of cerium oxide (CeO2) nanocrystals. Then, carbon quantum dots (CQDs) are encapsulated to form nanocomposites (CQD-Ce-RBC). This strategy is combined with photothermal therapy (PTT) for AD therapy. The application of RBC enhances the materials' biocompatibility and improves immune evasion. RBC-grown CeO2, the first application in the field of AD, demonstrates outstanding antioxidant properties. CQD acts as a chelating agent for copper ions, which prevents the aggregation of Aß. In addition, the thermal effect induced by near-infrared laser-induced CQD can break down Aß fibers and improve the permeability of the blood-brain barrier. In vivo experiments on APP/PS1 mice demonstrate that CQD-Ce-RBC combined with PTT effectively clears cerebral amyloid deposits and significantly enhances learning and cognitive abilities, thereby retarding disease progression. This innovative multipathway approach under light-induced conditions holds promise for AD treatment.
Assuntos
Doença de Alzheimer , Cério , Membrana Eritrocítica , Pontos Quânticos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Animais , Cério/química , Cério/farmacologia , Camundongos , Membrana Eritrocítica/química , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Humanos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/química , Raios Infravermelhos , Carbono/química , Carbono/farmacologia , Terapia Fototérmica , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Nanocompostos/química , Nanocompostos/uso terapêuticoRESUMO
Mitochondrial dysfunction and metal ion imbalance are recognized as pathological hallmarks of Alzheimer's Disease (AD), leading to deposition of ß-amyloid (Aß) thereby and inducing neurotoxicity, activating apoptosis, eliciting oxidative stress, and ultimately leading to cognitive impairment. In this study, the red blood cell membrane (RBC) was used as a vehicle for encapsulating carbon quantum dots (CQD) and polydopamine (PDA), creating a nanocomposite (PDA-CQD/RBC). This nanocomposite was combined with near-infrared light (NIR) for AD treatment. The RBC offers anti-immunorecognition properties to evade immune clearance, PDA exhibits enzyme-mimicking activity to mitigate oxidative stress damage, and CQD acts as a chelating agent for metal ions (Cu2+), effectively preventing Cu2+-mediated aggregation of Aß. Furthermore, the local heating induced by near-infrared laser irradiation can dismantle the formed Aß fibers and enhance the blood-brain barrier's permeability. Both in vitro and animal experiments have shown that PDA-CQD/RBC, in combination with NIR, mitigates neuroinflammation, and ameliorates behavioral deficits in mice. This approach targets multiple pathological pathways, surpassing the limitations of single-target treatments and enhancing therapeutic efficacy while decelerating disease progression.