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Tozorakimab is a high-affinity human immunoglobulin G1 monoclonal antibody that neutralizes interleukin (IL)-33, an IL-1 family cytokine. This phase 1, single-center, randomized, double-blind, placebo-controlled, single ascending dose study (NCT05070312) evaluated tozorakimab in a healthy Chinese population. Outcomes included the characterization of the pharmacokinetic (PK) profile and immunogenicity of tozorakimab. Safety outcomes included treatment-emergent adverse events (TEAEs) and clinical laboratory, electrocardiogram, and vital sign parameters. Healthy, non-smoking, male, and female Chinese participants aged 18-45 years with a body mass index 19-24 kg/m2 were enrolled. In total, 36 participants across 2 cohorts of 18 participants were randomized 2:1 to receive a single subcutaneous dose of tozorakimab (300 mg [2 mL] or 600 mg [4 mL]) or matching placebo (2 or 4 mL). Tozorakimab showed dose-dependent serum PK concentrations with an approximate monophasic distribution in serum over time and a maximum observed peak concentration of 20.1 and 33.7 µg/mL in the 300- and 600-mg cohorts, respectively. No treatment-emergent anti-drug antibodies for tozorakimab were observed in any of the participants. There were no clinically relevant trends in the occurrence of TEAEs across the treatment groups. There were no clinically relevant trends over time in clinical laboratory (hematology, clinical chemistry, and urinalysis), electrocardiogram, or vital sign parameters in any treatment group. Overall, tozorakimab demonstrated dose-dependent systemic exposure in healthy Chinese participants and was well tolerated, with no safety concerns identified in this study.
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Anticorpos Monoclonais Humanizados , Povo Asiático , Relação Dose-Resposta a Droga , Voluntários Saudáveis , Humanos , Método Duplo-Cego , Feminino , Masculino , Adulto , Injeções Subcutâneas , Adulto Jovem , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Pessoa de Meia-Idade , Adolescente , China , População do Leste AsiáticoRESUMO
Biochar is currently used as a phosphate adsorbent in water and subsequently as a soil amendment. In this study, modified biochar was prepared directly by co-pyrolysis of MgO and rice straw, and a preliminary ecotoxicological assessment was performed before the application of modified biochar to soil. The effects of single factors, such as pyrolysis temperature, dosage, pH, and coexisting ions, on phosphate adsorption performance were investigated. In addition, after phosphate adsorption, the effects of modified biochar leachate on the germination of corn and rice seeds were examined. The results showed that phosphate adsorption by the modified biochar first increased and then decreased as the pyrolysis temperature increased, with modified biochar prepared at 800 °C showing the greatest adsorption. In addition, a comprehensive cost analysis showed that the best phosphate adsorption effect of modified biochar was achieved at a dosage of 0.10â g and a solution pH of 3. In contrast, the presence of competitive coexisting ions, Cl- , NO3 - , CO3 2- , and SO4 2- , reduced the phosphate adsorption capacity of the modified biochar. The adsorption kinetics results revealed that the process of phosphate adsorption by the modified biochar was more in line with the pseudo-second-order model and dominated by chemisorption. Moreover, the adsorption isotherm results indicated that the process was more in line with the Langmuir model and dominated by monomolecular layer adsorption, with a maximum adsorption of 217.54â mg/g. Subsequent seed germination tests showed that phosphate-adsorbed modified biochar leachate had no significant effect on the germination rate of corn seeds, whereas it improved the germination rate of rice seeds. Together, these results provide guidance for the application of modified biochar firstly as an adsorbent of phosphate and subsequently as a soil remediator.
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Fosfatos , Poluentes Químicos da Água , Fosfatos/análise , Óxido de Magnésio , Germinação , Adsorção , Pirólise , Sementes/química , Poluentes Químicos da Água/análise , Carvão Vegetal/química , SoloRESUMO
OBJECTIVE: Exosomes in the central nervous system (CNS) have become an attractive area of research with great value. However, few bibliometric analysis has been conducted. The study aimed to visualize the scientific trends and research hotspots of exosomes in the CNS by bibliometric analysis. METHODS: All potential articles and reviews on exosomes in the CNS published in English from 2001 to 2021 were extracted from the Web of Science Core Collection. The visualization knowledge maps of critical indicators, including countries/regions, institutions, authors, journals, references, and keywords, were generated by CiteSpace and VOSviewer software. Besides, each domain's quantitative and qualitative analysis was also considered. RESULTS: A total of 2,629 papers were included. The number of exosomes-related publications and citations regarding CNS increased yearly. These publications came from 2,813 institutions in 77 countries/regions, led by the United States and China. Harvard University was the most influential institution, while the National Institutes of Health was the most critical funding source. We identified 14,468 authors, among which Kapogiannis D had the most significant number of articles and the highest H-index, while Théry C was the most frequently co-cited. The cluster analysis of keywords generated 13 clusters. In summary, the topic of biogenesis, biomarker, and drug delivery will serve as hotspots in future research. CONCLUSION: Exosomes-related CNS research has gained considerable attention in the past 20 years. The sources and biological functions of exosomes and their promising role in diagnosing and treating CNS diseases are considered hotspots in this field. The clinical translation of the results from exosomes-related CNS research will be of great importance in the future.
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Biochar modified by metal ions-particularly Mg-is typically used for the effective recovery of phosphorous. In this study, MgO-modified biochars were synthesized via the direct co-pyrolysis of MgO and raw materials such as rice straw, corn straw, Camellia oleifera shells, and branches from garden waste, which were labeled as MRS, MCS, MOT, and MGW, respectively. The resulting phosphate (PO) adsorption capacities and potential adsorption mechanisms were analyzed. The PO adsorption capacities of the biochars were significantly improved after the modification with MgO: MRS (24.71 ± 0.32 mg/g) > MGW (23.55 ± 0.46 mg/g) > MOT (15.23 ± 0.19 mg/g) > MCS (14.12 ± 0.21 mg/g). PO adsorption on the modified biochars was controlled by physical adsorption, precipitation, and surface inner-sphere complexation processes, although no electrostatic attraction was observed. Furthermore, PO adsorbed on modified biochars could be released under acidic, alkaline, and neutral conditions. The desorption efficiency of MRS was modest, indicating its suitability as a slow-release fertilizer.
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This work aimed to investigate the effect of pyrolysis temperature on the yield and properties of biochars synthesized from herbaceous and woody plants. Four typical materials, including two herbaceous plants (rice straw, corn straw) and two woody plants (camellia oleifera shells, garden waste), were used in the experiments under five operating temperatures (from 300 °C to 700 °C, with an interval of 100 °C). The results showed biochar derived from herbaceous plants had a significantly higher pH (from 7.68 to 11.29 for RS), electrical conductivity (EC, from 6.5 Ms cm-1 to 13.2 mS cm-1 for RS), cation exchange conductivity (CEC, from 27.81 cmol kg-1 to 21.69 cmol kg-1 for RS), and ash content (from 21.79% to 32.71% for RS) than the biochar from woody plants, but the volatile matter (VM, from 42.23% to 11.77% for OT) and specific surface area (BET, from 2.88 m2 g-1 to 301.67 m2 g-1 for OT) in the woody plant-derived biochar were higher. Except for CEC and VM, all the previously referred physicochemical characteristics in the as-prepared biochars increased with the increasing pyrolysis temperature, the H/C and O/C values of herbaceous and woody plant-derived biochar were lower than 0.9 and 0.3, respectively, confirming their potential as the material for carbon sequestration. The results revealed that biochar made from herbaceous plants was more suitable for acidic soil amendments. In contrast, woody plant-derived biochar were recommended to remove heavy metals in environmental remediation and water treatment.
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INTRODUCTION: Most adult cigarette smokers who use e-cigarettes are dual cigarette and e-cigarette (CC-EC) users, yet little is known about relative consumption of cigarettes to e-cigarettes and any associated harm reduction. METHODS: Rate of substitution from cigarettes to e-cigarettes at week 6 and change in biomarkers of exposure and potential harm were examined among dual dual cigarette and e-cigarette users [64/114 (56%); 35 Black, 29 Latino] in an e-cigarette switching randomized trial. RESULTS: Dual users averaged 79% substitution of cigarettes for e-cigarettes at week 6, resulting in a reduction from baseline of 70.0 ± 54.1 cigarettes per week (p < .001). Total nicotine consumption remained stable (baseline: 1160.5 ± 1042.1 pg/mL of cotinine, week 6: 1312.5 ± 1725.9 pg/mL of cotinine, p = .47), while significant reductions were seen in the potent lung carcinogen 4-(methylnitrosamino)-1-(3-pyridul)-1-butanol (NNAL) (-55.9 ± 88.6 ng/ml, p < .001), carbon monoxide (-6.3 ± 8.6 ppm, p < .001), and self-reported respiratory symptoms (-3.3 ± 8.0, p = .002). No significant changes were found in blood pressure or spirometry. Greater substitution from cigarettes to e-cigarettes was associated with larger reductions in NNAL (r = -.29, p = .02). CONCLUSIONS: The predominant dual-use pattern was characterized by regular e-cigarette and intermittent cigarette use. Findings demonstrate the short-term harm reduction potential of this dual-use pattern in Black and Latino smokers and suggest that the greatest benefit, aside from cessation of both products, is achieved by higher substitution of e-cigarettes for cigarettes. Findings need confirmation in a larger sample with longer follow-up in dual users with greater variability in the rate of substitution. CLINICALTRIALS.GOV IDENTIFIER: NCT03511001. IMPLICATIONS: Findings suggest short-term harm reduction potential of dual cigarette-e-cigarette use for Black and Latino smokers. Results also demonstrate the heterogeneity of dual-use, with the greatest harm reduction seen in dual users with higher rates of substitution from cigarettes to e-cigarettes. Study results should be confirmed in a full clinical trial with long-term follow-up to evaluate maintenance of dual-use patterns and associated harm reduction potential over time.
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Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Adulto , Redução do Dano , Hispânico ou Latino , Humanos , FumantesRESUMO
INTRODUCTION: Individuals with Alzheimer's disease (AD) broadly exhibit lower cardiorespiratory fitness (CRF) compared to cognitively healthy older adults. Other factors, such as increasing age and female sex, are also known to track with lower CRF levels. However, it is unclear how these factors together with AD diagnosis and genetic risk (apolipoprotein e4 ; APOE4) collectively affect CRF. METHODS: Our primary objective was to characterize the collective relationship of age, sex, APOE4 carrier status , and cognitive status (nondemented or AD) with two commonly reported CRF outcomes, VO2 max and oxygen uptake efficiency slope (OUES). To interrogate the unique and combined effect of age, sex, APOE4, and cognitive status on CRF, we pooled multiple datasets and tested several statistical models allowing all possible interactions. RESULTS: AD diagnosis was consistently associated with lower maximal CRF, which declined with increasing age. APOE4 was also associated with lower maximal CRF (VO2max), but only in male subjects. Submaximal CRF (OUES) was lower in APOE4 carriers of both sexes, although this difference converged in male subjects with advancing age. DISCUSSION: This multi-cohort analysis (n = 304) suggests that APOE4 carrier status and sex are important considerations for studies that evaluate maximal and submaximal CRF.
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Bessel-like beams with controllable rotation of local linear polarization upon propagation are generated, which in fact achieve the evolution of polarization states along the equator of the Poincaré sphere during propagation. Based on the amplitude-phase joint modulation method, the rotation direction and rate of polarizations of the Bessel-like beam can be controlled easily by adjusting the radial indices and intensity ratio of two superposed beams. A rotation angle of $\sim$â¼800 deg has been achieved after a propagation distance of 120 mm, corresponding to a rotation rate of $\sim$â¼6.7 deg/mm, which is about three times higher than in previous works.
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We introduce the concept of multifractal into vector optical fields (VOFs). We propose, design and generate new fractal VOFs-multifractal VOFs (MF-VOFs), in which multifractal structure and VOF act as the lattice and the base, respectively. We generate two kinds of MF-VOFs experimentally and explore their focusing behaviors. We also investigate the self-healing and information recovering abilities of MF-VOFs, comparing with those of single-fractal VOFs (SF-VOFs) when their lattices are composed of the same hierarchy of fractal geometries. The results show that MF-VOFs have better self-healing and information recovering abilities than that of traditional SF-VOFs, meaning that MF-VOFs have better ability to resist the information loss during the focusing and imaging processes. These properties may find potential applications in information transmission, optical communication, and so on.
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Polarization singularities have topological properties, because they can maintain their features invariably during propagation. The topological property can be destroyed by shifting the polarization singularities away from the central axis, and this destruction originates from the space separation of spin angular momentum components. We find that paired centrosymmetric off-axis polarization singularities can recover the topological property in the Fourier plane (reciprocal space), which belongs to the pseudo-topological property. We reveal that the pseudo-topological property is related to the invisible redistribution of both spin and orbital angular momentum states. We experimentally generate a series of Julia fractal vector optical fields with the pseudo-topological property. They may have potential applications in optical encryption and quantum information.
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Filamentation, as a universal femtosecond phenomenon that could occur in various nonlinear systems, has aroused extensive interest, owing to its underlying physics, complexity and applicability. It is always anticipated to realize the controllable and designable filamentation. For this aim, the crucial problem is how to actively break the symmetry of light-matter nonlinear interaction. A kind of extensively used approaches is based on the controllable spatial structure of optical fields involving phase, amplitude and polarization. Here we present an idea to control the optical field collapse by introducing optical anisotropy of matter as an additional degree of freedom, associated with polarization structure. Our theoretical prediction and experimental results reveal that the synergy of optical anisotropy and polarization structure is indeed a very effective means for controlling the optical field collapse, which has the robust feature against random noise.
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We present an inverse method to engineer uniform-intensity focal fields with arbitrary shape. Amplitude, phase, and polarization states, as adjustable parameters, are used to seek the desired focal fields in the non-iterative computational procedure. Our method can be applied to the cases with low and moderate numerical aperture (NA), in which case the feasibility and validity of our approach have been demonstrated in theory, simulation and experiment, respectively. For the case of higher NA, simulated results based on the Richards-Wolf diffraction integral are shown. We also made some discussions on the experiments with the higher NA. Our method should have wide applications in optical micro machining, optical trapping and so on.
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We introduce a general fractal lattice growth model, significantly expanding the application scope of the fractal in the realm of optics. This model can be applied to construct various kinds of fractal "lattices" and then to achieve the design of a great diversity of fractal vector optical fields (F-VOFs) combinating with various "bases". We also experimentally generate the F-VOFs and explore their universal focusing behaviors. Multiple focal spots can be flexibly enginnered, and the optical tweezers experiment validates the simulated tight focusing fields, which means that this model allows the diversity of the focal patterns to flexibly trap and manipulate micrometer-sized particles. Furthermore, the recovery performance of the F-VOFs is also studied when the input fields and spatial frequency spectrum are obstructed, and the results confirm the robustness of the F-VOFs in both focusing and imaging processes, which is very useful in information transmission.
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We introduce the concept of a fractal, which provides an alternative approach for flexibly engineering the optical fields and their focal fields. We propose, design, and create a new family of optical fields-fractal vector optical fields, which build a bridge between the fractal and vector optical fields. The fractal vector optical fields have polarization states exhibiting fractal geometry, and may also involve the phase and/or amplitude simultaneously. The results reveal that the focal fields exhibit self-similarity, and the hierarchy of the fractal has the "weeding" role. The fractal can be used to engineer the focal field.