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Scalable single-use adherent cell-based biomanufacturing platforms are essential for unlocking the full potential of cell and gene therapies. The primary objective of this study is to design and develop a novel fixed bed bioreactor platform tailored specifically for scaling up adherent cell culture. The bioreactor comprises a packed bed of vertically stacked woven polyethylene terephthalate mesh discs, sandwiched between two-fluid guide plates. Leveraging computational fluid dynamics modeling, we optimized bioreactor design to achieve uniform flow with minimal shear stress. Residence time distribution measurements demonstrated excellent flow uniformity with plug flow characteristics. Periodic media sampling coupled with offline analysis revealed minimal gradients of crucial metabolites (glucose, glutamine, lactate, and ammonia) across the bioreactor during cell growth. Furthermore, the bioreactor platform demonstrated high performance in automated cell harvesting, with ≈96% efficiency and ≈98% viability. It also exhibited linear scalability in both operational parameters and performance for cell culture and adeno-associated virus vector production. We developed mathematical models based on oxygen uptake rates to accurately predict cell growth curves and estimate biomass in real-time. This study demonstrates the effectiveness of the developed fixed-bed bioreactor platform in enabling scalable adherent cell-based biomanufacturing with high productivity and process control.
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Biomasa , Reactores Biológicos , Técnicas de Cultivo de Célula , Técnicas de Cultivo de Célula/métodos , Técnicas de Cultivo de Célula/instrumentación , Animales , Glucosa/metabolismo , Adhesión Celular , Proliferación Celular , Hidrodinámica , Células CHO , Cricetulus , Humanos , Diseño de EquipoRESUMEN
BACKGROUND: Diabetic foot ulcer is one of the most prevalent, serious, and costly consequences of diabetes, often associated with peripheral neuropathy and peripheral arterial disease. These ulcers contribute to high disability and mortality rates in patients and pose a major challenge to clinical management. OBJECTIVE: To systematically review the risk prediction models for post-healing recurrence in diabetic foot ulcer (DFU) patients, so as to provide a reference for clinical staff to choose appropriate prediction models. METHODS: The authors searched five databases (Cochrane Library, PubMed, Web of Science, EMBASE, and Chinese Biomedical Database) from their inception to September 23, 2023, for relevant literature. After data extraction, the quality of the literature was evaluated using the Predictive Model Research Bias Risk and Suitability Assessment tool (PROBAST). Meta-analysis was performed using STATA 17.0 software. RESULTS: A total of 9 studies involving 5956 patients were included. The recurrence rate after DFU healing ranged from 6.2 % to 41.4 %. Nine studies established 15 risk prediction models, and the area under the curve (AUC) ranged from 0.660 to 0.940, of which 12 models had an AUC≥0.7, indicating good prediction performance. The combined AUC value of the 9 validation models was 0.83 (95 % confidence interval: 0.79-0.88). Hosmer-Lemeshow test was performed for 10 models, external validation for 5 models, and internal validation for 6 models. Meta-analysis showed that 14 predictors, such as age and living alone, could predict post-healing recurrence in DFU patients (p < 0.05). CONCLUSION: To enhance the quality of these risk prediction models, there is potential for future improvements in terms of follow-up duration, model calibration, and validation processes.
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BACKGROUND: Intensive care unit (ICU)-acquired weakness (ICU-AW) is a critical complication that significantly worsens patient prognosis. It is widely thought that risk prediction models can be harnessed to guide preventive interventions. While the number of ICU-AW risk prediction models is increasing, the quality and applicability of these models in clinical practice remain unclear. OBJECTIVE: The objective of this study was to systematically review published studies on risk prediction models for ICU-AW. METHODS: We searched electronic databases (PubMed, Web of Science, The Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), China National Knowledge Infrastructure (CNKI), China Science and Technology Periodical Database (VIP), and Wanfang Database) from inception to October 2023 for studies on ICU-AW risk prediction models. Two independent researchers screened the literature, extracted data, and assessed the risk of bias and applicability of the included studies. RESULTS: A total of 2709 articles were identified. After screening, 25 articles were selected, encompassing 25 risk prediction models. The area under the curve for these models ranged from 0.681 to 0.926. Evaluation of bias risk indicated that all included models exhibited a high risk of bias, with three models demonstrating poor applicability. The top five predictors among these models were mechanical ventilation duration, age, Acute Physiology and Chronic Health Evaluation II score, blood lactate levels, and the length of ICU stay. The combined area under the curve of the ten validation models was 0.83 (95% confidence interval: 0.77-0.88), indicating a strong discriminative ability. CONCLUSIONS: Overall, ICU-AW risk prediction models demonstrate promising discriminative ability. However, further optimisation is needed to address limitations, including data source heterogeneity, potential biases in study design, and the need for robust statistical validation. Future efforts should prioritise external validation of existing models or the development of high-quality predictive models with superior performance. REGISTRATION: The protocol for this study is registered with the International Prospective Register of Systematic Reviews (registration number: CRD42023453187).
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The ionic conductivity, phase components, and microstructures of LATP depend on its synthesis process. However, their relative importance and their interactions with synthesis process parameters (such as source materials, calcination temperature, and sintering temperature) remain unclear. In this work, different source materials were used to prepare LATP via the solid-state reaction method under different calcination and sintering temperatures, and an analysis via orthogonal experiments and machine learning was used to systematically study the effects of the process parameters. Sintering temperatures had the greatest effect on the total ionic conductivity of LATP pellets, followed by the sources and calcination temperatures. Sources, as the foundational factors, directly determine the composition of a major secondary phase of LATP pellets, which influences the whole process. The calcination temperature had limited impact on the ion conductivity of LATP pellets if pellets were sintered under the optimal temperature. The sintering temperature is the most important factor that influences the ion conductivity by eliminating most secondary phases and altering the microstructure of LATP, including the intergranular contact, grain size, relative densities, etc. This work offers a novel perspective to comprehend the synthesis of solid-state electrolytes beyond LATP.
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Cation-disordered rock-salt (DRX) materials receive intensive attention as a new class of cathode candidates for high-capacity lithium-ion batteries (LIBs). Unlike traditional layered cathode materials, DRX materials have a three-dimensional (3D) percolation network for Li+ transportation. The disordered structure poses a grand challenge to a thorough understanding of the percolation network due to its multiscale complexity. In this work, we introduce the large supercell modeling for DRX material Li1.16Ti0.37Ni0.37Nb0.10O2 (LTNNO) via the reverse Monte Carlo (RMC) method combined with neutron total scattering. Through a quantitative statistical analysis of the material's local atomic environment, we experimentally verified the existence of short-range ordering (SRO) and uncovered an element-dependent behavior of transition metal (TM) site distortion. A displacement from the original octahedral site for Ti4+ cations is pervasive throughout the DRX lattice. Density functional theory (DFT) calculations revealed that site distortions quantified by the centroid offsets could alter the migration barrier for Li+ diffusion through the tetrahedral channels, which can expand the previously proposed theoretical percolating network of Li. The estimated accessible Li content is highly consistent with the observed charging capacity. The newly developed characterization method here uncovers the expandable nature of the Li percolation network in DRX materials, which may provide valuable guidelines for the design of superior DRX materials.
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Thoracic aortic aneurysm is one of the manifestations of Marfan syndrome (MFS) that is known to affect men more severely than women. However, the incidence of MFS is similar between men and women. The aim of this study is to show that during pathological aortic dilation, sex-dependent severity of thoracic aortopathy in a mouse model of MFS translates into sex-dependent alterations in cells and matrix of the ascending aorta, consequently affecting aortic biomechanics. Fibrillin-1 C1041G/+ (Het) mice were used as a mouse model of MFS. Ultrasound measurements from 3 to 12 mo showed increased aortic diameter in Het aorta, with larger percentage increase in diameter for males compared with females. Immunohistochemistry showed decreased contractile smooth muscle cells in Het aortic wall compared with healthy aorta, which was accompanied by decreased contractility measured by wire myography. Elastin autofluorescence, second-harmonic generation microscopy of collagen fibers, and passive biomechanical assessments using myography showed more severe damage to elastin fibers, increased medial fibrosis, and increased stiffness of the aortic wall in MFS males but not females. Male and female Het mice showed increased expression of Sca-1-positive adventitial progenitor cells versus controls at young ages. In agreement with clinical data, Het mice demonstrate sex-dependent severity of thoracic aortopathy. It was also shown that aging exacerbates the disease state especially for males. Our findings suggest that female mice are protected from progression of aortic dilation at early ages, leading to a lag in aneurysm growth.NEW & NOTEWORTHY Male Fbn1C1041G/+ mice show more severe thoracic aortic changes compared with females, especially at 12 mo of age. Up to 6 mo of age, Sca-1+ smooth muscle progenitor cells are more abundant in the adventitia of both male and female Fbn1 Het mice compared with wild types (WTs). Male and female Het mice show similar patterns of expression of Sca-1+ cells at early ages.
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Aorta Torácica/patología , Modelos Animales de Enfermedad , Síndrome de Marfan/genética , Animales , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/crecimiento & desarrollo , Femenino , Fibrilina-1/genética , Masculino , Síndrome de Marfan/diagnóstico por imagen , Síndrome de Marfan/patología , Ratones , Ratones Endogámicos C57BL , Caracteres SexualesRESUMEN
Measuring the spectral response (SR) of large-area (>100cm2) luminescent solar concentrators (LSCs) has proven difficult because common laboratory photovoltaic (PV) instruments that offer monochromatic incidence measure devices with limited sizes (typically <50cm2). This report addresses this issue through a method called regional measurements. In this method, large-area LSCs are configured to small surface and edge regions, which are sequentially illuminated and measured, respectively. The measured SRs of large-area LSCs are consistent with those from the conventional method and the Monte Carlo ray-tracing simulation. This method is also applied to analyze scattering effects in the LSCs, showing the relationships of the scattering-induced power gain and power loss to the surface root-mean-squared roughness (Rq) of the devices. The results explain why the PV performance of the LSCs can be improved through proper surface scattering treatment.
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Harvesting solar energy for catalytic conversion of CO2 into valuable chemical fuels/feedstocks is an attractive yet challenging strategy to realize a sustainable carbon-cycle utilization. Homogeneous catalysts typically exhibit higher activity and selectivity as compared with heterogeneous counterparts, benefiting from their atomically dispersed catalytic sites and versatile coordination structures. However, it is still a "black box" how the coordination and electronic structures of catalysts dynamically evolve during the reaction, forming the bottleneck for understanding their reaction pathways. Herein, we demonstrate to track the mechanistic pathway of photocatalytic CO2 reduction using a terpyridine nickel(II) complex as a catalyst model. Integrated with a typical homogeneous photosensitizer, the catalytic system offers a high selectivity of 99% for CO2-to-CO conversion with turnover number and turnover frequency as high as 2.36 × 107 and 385.6 s-1, respectively. We employ operando and time-resolved X-ray absorption spectroscopy, in combination with other in situ spectroscopic techniques and theoretical computations, to track the intermediate species of Ni catalyst in the photocatalytic CO2 reduction reaction for the first time. Taken together with the charge dynamics resolved by optical transient absorption spectroscopy, the investigation elucidates the full mechanistic reaction pathway including some key factors that have been often overlooked. This work opens the "black box" for CO2 reduction in the system of homogeneous catalysts and provides key information for developing efficient catalysts toward artificial photosynthesis.
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In this study, a polymer dispersed cholesteric liquid crystal (PDChLC) film obtained via a one-step fabrication technique based on photopolymerization of a thiol-acrylate reaction system was prepared and characterized for the first time. The effects of the chiral dopant, the influence of thiol monomer functionality and content on the morphology and subsequent performance of the PDChLC films were systematically investigated. It was demonstrated that the addition of a small amount of chiral dopant slightly increased the driving voltage, but decreased the off-state transmittance significantly. Furthermore, scanning electron micrographs (SEM) shown that the liquid crystal (LC) droplet size decreased at first and then increased with the increasing amount of thiol monomer functionality, while increasing the thiol content increased the LC droplet size. Correspondingly, the electro-optical switching behavior was directly dependent on LC droplet size. By tuning the raw material composition, PDChLC film with optimized electro-optical performance was prepared.
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Acrilatos/química , Cristales Líquidos/química , Polímeros/química , Compuestos de Sulfhidrilo/química , Electricidad , Luz , Microscopía Electrónica de Rastreo , Estructura Molecular , Fenómenos ÓpticosRESUMEN
Polymer-dispersed liquid crystal (PDLC) films were prepared by the ultraviolet-light-induced polymerization of photopolymerizable monomers in nematic liquid crystal/chiral dopant/thiol-acrylate reaction monomer composites. The effects of the chiral dopant and crosslinking agents on the electro-optical properties of the PDLC films were systematically investigate. While added the chiral dopant S811 into the PDLC films, the initial off-state transmittance of the films was decreased. It was found that the weight ratio among acrylate monomers, thiol monomer PETMP and the polymercaptan Capcure 3-800 showed great influence on the properties of the fabricated PDLC films because of the existence of competition between thiol-acrylate reaction and acrylate monomer polymerization reaction. While adding polymercaptans curing agent Capcure 3-800 with appropriate concentration into the PDLC system, lower driven voltage and higher contrast ratio were achieved. This made the polymer network and electro-optical properties of the PDLC films easily tunable by the introduction of the thiol monomers.
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Acrilatos/química , Cristales Líquidos/química , Polímeros/química , Compuestos de Sulfhidrilo/química , Óptica y Fotónica , Procesos Fotoquímicos , Polimerizacion , Rayos UltravioletaRESUMEN
Plant viruses transmitted by arthropods, as an important biotic factor, may not only directly affect the yield and quality of host plants, and development, physiological characteristics and ecological performances of their vector arthropods, but also directly or indirectly affect the non-vector herbivorous arthropods and their natural enemies in the same ecosystem, thereby causing influences to the whole agro-ecosystem. This paper reviewed the progress on the effects of plant viruses on herbivorous arthropods, including vector and non-vector, and their natural enemies, and on their ecological mechanisms to provide a reference for optimizing the management of vector and non-vector arthropod populations and sustainable control of plant viruses in agro-ecosystem.
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Artrópodos/virología , Vectores de Enfermedades , Virus de Plantas , Agricultura , Animales , Ecosistema , HerbivoriaRESUMEN
In order to clarify the impacts of southern rice black-streaked dwarf virus (SRBSDV) infection on rice plants, rice planthoppers and natural enemies, differences in nutrients and volatile secondary metabolites between infected and healthy rice plants were examined. Furthermore, the impacts of virus-mediated changes in plants on the population growth of non-vector brown planthopper (BPH), Nilaparvata lugens, and the selectivity and parasitic capability of planthopper egg parasitoid Anagrus nilaparvatae were studied. The results showed that rice plants had no significant changes in amino acid and soluble sugar contents after SRBSDV infection, and SRBSDV-infected plants had no significant effect on population growth of non-vector BPH. A. nilaparvatae preferred BPH eggs both in infected and healthy rice plants, and tended to parasitize eggs on infected plants, but it had no significant preference for infected plants or healthy plants. GC-MS analysis showed that tridecylic aldehyde occurred only in rice plants infected with SRBSDV, whereas octanal, undecane, methyl salicylate and hexadecane occurred only in healthy rice plants. However, in tests of behavioral responses to these five volatile substances using a Y-tube olfactometer, A. nilaparvatae did not show obvious selectivity between single volatile substances at different concentrations and liquid paraffin in the control group. The parasitic capability of A. nilaparvatae did not differ between SRBSDV-infected plants and healthy plant seedlings. The results suggested that SRBSDV-infected plants have no significant impacts on the non-vector planthopper and its egg parasitoid, A. nilaparvatae.
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Hemípteros/fisiología , Insectos Vectores/fisiología , Oryza/metabolismo , Enfermedades de las Plantas/virología , Aminoácidos/metabolismo , Animales , Conducta Animal , Metabolismo de los Hidratos de Carbono , Femenino , Hemípteros/parasitología , Hemípteros/virología , Especificidad del Huésped , Interacciones Huésped-Parásitos , Insectos Vectores/parasitología , Insectos Vectores/virología , Masculino , Metaboloma , Oryza/parasitología , Oryza/virología , Óvulo/virología , Enfermedades de las Plantas/parasitología , Virus de Plantas , Crecimiento DemográficoRESUMEN
We report a thin-film optical diode written into thin films of a liquid-crystalline polymer (LCP), which is based on the photoinduced LC-to-isotropic phase transition of LCPs. The interference pattern between a collimated and a focused UV laser beam is imprinted as chirped volume-phase gratings in photoresponsive LCP films and no further processing steps like development or liftoff are required for the fabrication. The resultant thin-film device not only possesses the fundamental functions of an optical lens for laser beam focusing, but also shows diode effects with the focusing/defocusing function dependent on the direction of light incidence and orientation of the device. Furthermore, this photonic thin-film lens exhibits a spatially tunable spectroscopic response, revealing a unique physics of secondary excitations of resonance modes of the single-layer LCP waveguide grating structures. This reveals the mechanisms for the focusing/defocusing of laser beams by chirped grating structures. Erasability and reconstructibility of the photoresponsive LCPs guarantee rewritability of the thin-film diode lens.