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1.
Chem Soc Rev ; 53(10): 5149-5189, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38566609

RESUMEN

The electrochemical reduction of CO2 into value-added chemicals has been explored as a promising solution to realize carbon neutrality and inhibit global warming. This involves utilizing the electrochemical CO2 reduction reaction (CO2RR) to produce a variety of single-carbon (C1) and multi-carbon (C2+) products. Additionally, the electrolyte solution in the CO2RR system can be enriched with nitrogen sources (such as NO3-, NO2-, N2, or NO) to enable the synthesis of organonitrogen compounds via C-N coupling reactions. However, the electrochemical conversion of CO2 into valuable chemicals still faces challenges in terms of low product yield, poor faradaic efficiency (FE), and unclear understanding of the reaction mechanism. This review summarizes the promising strategies aimed at achieving selective production of diverse carbon-containing products, including CO, formate, hydrocarbons, alcohols, and organonitrogen compounds. These approaches involve the rational design of electrocatalysts and the construction of coupled electrocatalytic reaction systems. Moreover, this review presents the underlying reaction mechanisms, identifies the existing challenges, and highlights the prospects of the electrosynthesis processes. The aim is to offer valuable insights and guidance for future research on the electrocatalytic conversion of CO2 into carbon-containing products of enhanced value-added potential.

2.
Nano Lett ; 23(1): 291-297, 2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36563295

RESUMEN

Electrochemical conversion of CO2 into high-value-added chemicals has been considered a promising route to achieve carbon neutrality and mitigate the global greenhouse effect. However, the lack of highly efficient electrocatalysts has limited its practical application. Herein, we propose an ultrafast and green electric explosion method to batch-scale prepare spherical indium (In) nanocrystals (NCs) with abundant metal defects toward high selective electrocatalytic CO2 reduction (CO2RR) to HCOOH. During the electric explosion synthesis process, the Ar atmosphere plays a significant role in forming the spherical In NCs with abundant metal defects instead of highly crystalline In2O3 NCs formed under an air atmosphere. Analysis results reveal that the In NCs possess ultrafast catalytic kinetics and reduced onset potential, which is ascribed to the formation of rich metal defects serving as effective catalytic sites for converting CO2 into HCOOH. This work provides a feasible strategy to massively produce efficient In-based electrocatalysts for electrocatalytic CO2-to-formate conversion.

3.
Nano Lett ; 23(22): 10140-10147, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37930176

RESUMEN

Massive production of practical metal or alloy based electrocatalysts for electrocatalytic CO2 reduction reaction is usually limited by energy-extensive consumption, poor reproducibility, and weak adhesion on electrode substrates. Herein, we report the ultrafast thermal shock synthesis and porosity engineering of free-standing Cu-Bi bimetallic nanofoam electrocatalysts with 3D hierarchical porous structure and easily adjustable compositions. During the thermal shock process, the rapid heating and cooling steps in several seconds result in strong interaction between metal nanopowders to form multiphase nanocrystallines with abundant grain boundaries and metastable CuBi intermetallic phase. The subsequent porosity engineering process via acid etching and electroreduction creates highly porous Cu-Bi structures that can increase electrochemically active surface area and facilitate mass/charge transfer. Among the Cu-Bi nanofoam electrodes with different Cu/Bi ratios, the Cu4Bi nanofoam exhibited the highest formate selectivity with a Faradaic efficiency of 92.4% at -0.9 V (vs reversible hydrogen electrode) and demonstrated excellent operation stability.

4.
Small ; 19(39): e2302650, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37264736

RESUMEN

Metallic zinc (Zn) is a highly promising anode material for aqueous energy storage systems due to its low redox potential, high theoretical capacity, and low cost. However, rampant dendrites/by-products and torpid Zn2+ transfer kinetics at electrode/electrolyte interface severely threaten the cycling stability, which deteriorate the electrochemical performance of Zn-ion batteries. Herein, an interfacial engineering strategy to construct alkaline earth fluoride modified metal Zn electrodes with long lifespan and high capacity retention is reported. The compact fluoride layer is revealed to guide uniform Zn stripping/plating and accelerate the transfer/diffusion of Zn2+ via Maxwell-Wagner polarization. A series of in situ and ex situ spectroscopic studies verified that the fluoride layer can guide uniform Zn stripping/plating. Electrochemical kinetics analyses reveal that positive effect on the removal of Zn2+ solvation sheath provided by fluoride layer. Meanwhile, this fluoride coating layer can act as a barrier between the Zn electrode and electrolyte, providing a high electrode overpotential toward hydrogen evolution reaction to hold back H2 evolution. Consequently, the fluoride-modified Zn anode exhibited a capacity retention of 88.2% after 4000 cycles under10 A g-1 . This work opens up a new path to interface engineering for propelling the exploration of advanced rechargeable aqueous Zn-ion batteries.

5.
Liver Int ; 43(5): 1096-1106, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36648384

RESUMEN

BACKGROUND & AIMS: Human neutrophil peptides (HNP)-1, -2 and -3 are the most abundant proteins in neutrophil azurophilic granules and are rapidly released via neutrophil degranulation upon activation. The aims of our study were to assess the role of HNP1-3 as biomarkers of disease severity in patients with decompensated cirrhosis and their value in predicting short-term mortality. METHODS: In this study, 451 patients with acutely decompensated cirrhosis (AD) were enrolled at the two medical centres. Overall, 281 patients were enrolled as the training cohort from October 2015 to April 2019, and 170 patients were enrolled as the validation cohort from June 2020 to February 2021. Plasma HNP1-3 levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma HNP1-3 increased stepwise with disease severity (compensated cirrhosis: 0.3 (0.2-0.4); AD without acute-on-chronic liver failure (ACLF): 1.9 (1.3-4.8); ACLF-1: 2.3 (1.8-6.1); ACLF-2: 5.6 (2.9-12.3); ACLF-3: 10.3 (5.7-17.2) ng/ml). From the multivariate Cox regression analysis, HNP1-3 emerged as independent predictors of mortality at 30 and 90 days. Similar results were observed in the subgroup analysis. On ROC analysis, plasma HNP1-3 showed better predictive accuracy for 30- and 90-day mortality (area under the receiver operating characteristic (AUROC) of 0.850 and 0.885, respectively) than the neutrophil-to-lymphocyte ratio (NLR) and similar accuracy as end-stage liver disease (MELD: 0.881 and 0.874) and chronic liver failure-sequential organ failure (CLIF-SOFA: 0.887 and 0.878). CONCLUSIONS: Plasma HNP1-3 levels were closely associated with disease severity and might be used to identify patients with AD at high risk of short-term mortality.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Enfermedad Hepática en Estado Terminal , Humanos , Pronóstico , Neutrófilos , Biomarcadores , Cirrosis Hepática/complicaciones , Gravedad del Paciente , Péptidos , Índice de Severidad de la Enfermedad
6.
Nano Lett ; 22(6): 2529-2537, 2022 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-35266387

RESUMEN

Electrochemically converting nitrate to ammonia is a promising route to realize artificial nitrogen recycling. However, developing highly efficient electrocatalysts is an ongoing challenge. Herein, we report the construction of stable and redox-active zirconium metal-organic frameworks (Zr-MOFs) based on Zr6 nanoclusters and redox-reversible tetrathiafulvalene (TTF) derivatives as inorganic nodes and organic linkers, respectively. The redox-active Zr-MOF can facilitate the in situ reduction of noble metal precursors free of external reductants and realize the uniform nucleation of noble metal nanodots (NDs) on Zr-MOF, achieving the preparation of M-NDs/Zr-MOF (M = Pd, Ag, or Au). The highly porous Zr-MOF with good conductivity can facilitate the mass transfer process. Among the M-NDs/Zr-MOF catalysts, Pd-NDs/Zr-MOF exhibits the highest electrocatalytic activity, delivering a NH3 yield of 287.31 mmol·h-1·g-1cat. and a Faradaic efficiency of 58.1%. The proposed interfacial reduction nucleation strategy for anchoring M NDs on Zr-MOFs can be applied to other challenging energy conversion reactions.

7.
Small ; 17(41): e2103051, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34510738

RESUMEN

Developing emerging materials for high energy-density lithium-sulfur (Li-S) batteries is of great significance to suppress the shuttle effect of polysulfides and to accommodate the volumetric change of sulfur. Here, a novel porous microcapsule system containing a carbon nanotubes/tin dioxide quantum dots/S (CNTs/QDs/S) composite core and a porous shell prepared through a liquid-driven coaxial microfluidic method as Li-S battery cathode is developed. The encapsulated CNTs in the microcapsules provide pathways for electron transport; SnO2 QDs on CNTs immobilize the polysulfides by strong adsorption, which is verified by using density functional theory calculations on binding energies. The porous shell of the microcapsule is beneficial for ion diffusion and electrolyte penetration. The void inside the microcapsule accommodates the volumetric change of sulfur. The Li-S battery based on the porous CNTs/QDs/S microcapsules displays a high capacity of 1025 mAh g-1 after 100 cycles at 0.1 C. When the sulfur loading is 2.03 mg cm-2 , the battery shows a stable cycling life of 700 cycles, a Coulombic efficiency exceeding 99.9%, a recoverable rate-performance during repeated tests, and a good temperature tolerance at both -5 and 45 °C, which indicates a potential for applications at different conditions.

8.
Artif Organs ; 45(7): 762-769, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33326621

RESUMEN

Our aim was to investigate the effect of artificial liver blood purification treatment on the survival of severe/critical patients with coronavirus disease 2019 (COVID-19). A total of 101 severe and critical patients with coronavirus SARS-CoV-2 infection were enrolled in this open, case-control, multicenter, prospective study. According to the patients' and their families' willingness, they were divided into two groups. One was named the treatment group, in which the patients received artificial liver therapy plus comprehensive treatment (n = 50), while the other was named the control group, in which the patients received only comprehensive treatment (n = 51). Clinical data and laboratory examinations, as well as the 28-day mortality rate, were collected and analyzed. Baseline data comparisons on average age, sex, pre-treatment morbidity, initial symptoms, vital signs, pneumonia severity index score, blood routine examination and biochemistry indices etc. showed no difference between the two groups. Cytokine storm was detected, with a significant increase of serum interleukin-6 (IL-6) level. The serum IL-6 level decreased from 119.94 to 20.49 pg/mL in the treatment group and increased from 40.42 to 50.81 pg/mL in the control group (P < .05), indicating that artificial liver therapy significantly decreased serum IL-6. The median duration of viral nucleic acid persistence was 19 days in the treatment group (ranging from 6 to 67 days) and 17 days in the control group (ranging from 3 to 68 days), no significant difference was observed (P = .36). As of 28-day follow-up,17 patients in the treatment group experienced a median weaning time of 24 days, while 11 patients in the control group experienced a median weaning time of 35 days, with no significant difference between the two groups (P = .33). The 28-day mortality rates were 16% (8/50) in the treatment group and 50.98% (26/51) in the control group, with a significant difference (z = 3.70, P < .001). Cytokine storm is a key factor in the intensification of COVID-19 pneumonia. The artificial liver therapy blocks the cytokine storm by clearing inflammatory mediators, thus preventing severe cases from progressing to critically ill stages and markedly reducing short-term mortality.


Asunto(s)
COVID-19/terapia , Síndrome de Liberación de Citoquinas/prevención & control , Hígado Artificial , Intercambio Plasmático/instrumentación , Anciano , Biomarcadores/sangre , COVID-19/sangre , COVID-19/mortalidad , COVID-19/virología , Estudios de Casos y Controles , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/mortalidad , Síndrome de Liberación de Citoquinas/virología , Citocinas/sangre , Femenino , Mortalidad Hospitalaria , Interacciones Huésped-Patógeno , Humanos , Masculino , Persona de Mediana Edad , Intercambio Plasmático/efectos adversos , Intercambio Plasmático/mortalidad , Estudios Prospectivos , SARS-CoV-2/patogenicidad , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Carga Viral
9.
Nanotechnology ; 31(45): 455402, 2020 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-32808597

RESUMEN

High-energy-density secondary batteries are required for many applications such as electric vehicles. Lithium-sulfur (Li-S) batteries are receiving broad attention because of their high theoretical energy density. However, the large volume change of sulfur during cycling, poor conductivity, and the shuttle effect of sulfides severely restrict the Li-storage performance of Li-S batteries. Herein, we present a novel core-shell nanocomposite consisting of a sulfur core and a hydrogel polypyrrole (PPy) shell, enabling an ultra-high sulfur content of about 98.4% within the composite, which greatly exceeds many other conventional composites obtained by coating sulfur onto some hosts. In addition, the void inside the core-shell structure effectively accommodates the volume change; the conductive PPy shell improves the conductivity of the composite; and PPy is able to adsorb polysulfides, suppressing the shuttle effect. After cycling for 200 cycles, the prepared S@void@PPy composite retains a stable capacity of 650 mAh g-1, which is higher than the bare sulfur particles. The composite also exhibits a fast Li ion diffusion coefficient. Furthermore, the density functional theory calculations show the PPy shell is able to adsorb polysulfides efficiently, with a large adsorption energy and charge density transfer.

10.
J Environ Manage ; 196: 127-136, 2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-28284130

RESUMEN

Removing heavy metal ions from aqueous solutions is one of the most challenging separations. In situ oxidized Fe3O4 membranes using 316L porous stainless steel filter tube have shown great potential for removing anion Cr(VI). Here we report the performances of the in situ oxidized Fe3O4 membranes for removing two toxic cations Cd(II) and Pb(II) commonly existing in water and their potential applications for drinking water purification. The membranes exhibited high removal efficiency: 97% at pH 9.0 for Cd(II) of 1.0 mg/L initial concentration and 100% at pH 5.0-6.0 for Pb(II) of 5.0 mg/L initial concentration. The maximum adsorption capabilities were estimated at 0.800 mg/g and 2.251 mg/g respectively for Cd(II) and Pb(II) at 318 K by the Langmuir model. Results of batch tests revealed the existence of electrostatic attraction and chemisorption. XRD and FT-IR analyses indicated that the chemisorption might be the insertion of Cd(II) and Pb(II) into the Fe3O4 crystal faces of 311 and 511 to form mononuclear or binuclear coordination with O atoms of Fe-O6 groups. Competitive adsorption of Cd(II) and Pb(II) in binary solutions revealed a preferential adsorption for Pb(II). Na2EDTA solution was used to regenerate the membranes, and the maximum desorption ratio was 90.29% and 99.75% respectively for Cd(II) and Pb(II). The membranes were able to efficiently lower Cd(II) and Pb(II) concentrations to meet the drinking water standards recommended by the World Health Organization and are promising for engineering applications aimed at drinking water purification.


Asunto(s)
Cadmio , Plomo , Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Concentración de Iones de Hidrógeno , Espectroscopía Infrarroja por Transformada de Fourier , Acero Inoxidable
11.
Clin Exp Pharmacol Physiol ; 41(9): 643-9, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24837195

RESUMEN

The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has emerged as a useful predictor of long-term outcome in NAFLD patients. We evaluated the predictive performance of the NFS for overall mortality in a Chinese population with NAFLD. All NAFLD patients diagnosed ultrasonographically at Xixi Hospital of Hangzhou between 1996 and 2011 were retrospectively recruited to the study. Outcome was determined by interview and causes of death were confirmed by medical records. The area under the receiver operating characteristic curve (AUCROC ) was used to determine the predictive accuracy of the NFS, BARD (body mass index, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, diabetes) score, FIB-4 index and the AST/platelet ratio index (APRI) for mortality. Data from a total of 180 eligible patients (median age 39 years; 96 men) were analysed, with 12 deaths over a median follow-up period of 6.6 years (range 0.5-14.8 years). Using Cox model analysis, the NFS as a continuous variable was identified as the only predictor for all-cause mortality (hazard ratio 2.743, 95% confidence interval (CI) 1.670-4.504). The NFS yielded the highest AUCROC of 0.828 (95% CI 0.728-0.928, P < 0.05), followed by the FIB-4 index, APRI and BARD score (AUCROC 0.806 (P < 0.05), 0.732 (P < 0.05) and 0.632, respectively). The data indicated that the NFS is a useful predictor of 6.6-year all-cause mortality for Chinese patients with NAFLD.


Asunto(s)
Causas de Muerte , Cirrosis Hepática/patología , Enfermedad del Hígado Graso no Alcohólico/patología , Valor Predictivo de las Pruebas , Adulto , Pueblo Asiatico/estadística & datos numéricos , China/epidemiología , Femenino , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/mortalidad , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/mortalidad , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Ultrasonografía , Adulto Joven
12.
Artículo en Inglés | MEDLINE | ID: mdl-38597358

RESUMEN

Thermoresponsive wound dressings with real-time monitoring and on-demand drug delivery have gained significant attention recently. However, such smart systems with stable temperature adjustment and drug release control are still lacking. Here, a novel smart fabric is designed for wound management with thermoresponsive drug delivery and simultaneously temperature monitoring. The triple layers of the fabrics are composed of the drug-loaded thermoresponsive nanofiber film, the MXene-optimized joule heating film, and the FPCB control chip. The precise and stable temperature stimulation can be easily achieved by applying a low voltage (0-4 V) to the heating film, achieving the temperature control ranging from 25 to 130 °C. And the temperature of the wound region can be monitored and adjusted in real time, demonstrating an accurate and low-voltage joule heating capability. Based on that, the drug-loaded film achieved precise thermoresponsive drug release and obtained significant antibacterial effects in vitro. The in vivo experiments also proved the hybrid fabric system with a notable antibacterial effect and accelerated wound healing process (about 30% faster than the conventional gauze group).

13.
J Agric Food Chem ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842427

RESUMEN

Heavy metal contamination in soils poses a significant environmental threat to human health. This study examines the effects of the chiral herbicide napropamide (NAP) on Arabidopsis thaliana, focusing on growth metrics and cadmium (Cd) accumulation. R-NAP does not adversely affect plant growth compared to the control, whereas S-NAP significantly reduces root length and fresh weight. Notably, R-NAP markedly increases Cd accumulation in the shoots, exceeding levels observed in the control and S-NAP. This increase coincides with reduced photosynthetic efficiency. Noninvasive electrode techniques reveal a higher net Cd absorption flux in the root mature zone under R-NAP than S-NAP, although similar to the control. Transcriptomic analysis highlights significant stereoisomer differences in Cd transporters, predominantly under R-NAP treatment. SEM and molecular docking simulations support that R-NAP primarily upregulates transporters such as HMA4. The results suggest careful management of herbicides like R-NAP in contaminated fields to avoid excessive heavy metal buildup in crops.

14.
Clin Exp Med ; 24(1): 45, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38413535

RESUMEN

Systemic inflammation is related to disease progression and prognosis in patients with advanced cirrhosis. However, the mechanisms underlying the initiation of inflammation are still not fully understood. The role of CD169+ monocyte/macrophage in cirrhotic systemic inflammation was undetected. Flow cytometry analysis was used to detect the percentage and phenotypes of CD169+ monocytes as well as their proinflammatory function in patient-derived cirrhotic tissue and blood. Transcriptome differences between CD169+ and CD169- monocytes were also compared. Additionally, a mouse model with specific depletion of CD169+ monocytes/macrophages was utilized to define their role in liver injury and fibrosis. We observed increased CD169 expression in monocytes from cirrhotic patients, which was correlated with inflammatory cytokine production and disease progression. CD169+ monocytes simultaneously highly expressed M1- and M2-like markers and presented immune-activated profiles. We also proved that CD169+ monocytes robustly prevented neutrophil apoptosis. Depletion of CD169+ monocytes/macrophages significantly inhibited inflammation and liver necrosis in acute liver injury, but the spontaneous fibrin resolution after repeated liver injury was impaired. Our results indicate that CD169 defines a subset of inflammation-associated monocyte that correlates with disease development in patients with cirrhosis. This provides a possible therapeutic target for alleviating inflammation and improving survival in cirrhosis.


Asunto(s)
Cirrosis Hepática , Monocitos , Animales , Ratones , Humanos , Cirrosis Hepática/patología , Inflamación , Progresión de la Enfermedad , Macrófagos/metabolismo
15.
J Hazard Mater ; 476: 134909, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38905979

RESUMEN

Developing highly-efficient electrocatalysts for the nitrate reduction reaction (NITRR) is a persistent challenge. Here, we present the successful synthesis of 14 amorphous/low crystallinity metal nanofilms on three-dimensional carbon fibers (M-NFs/CP), including Al, Ti, Mn, Fe, Co, Ni, Cu, Zn, Ag, In, Sn, Pb, Au, or Bi, using rapid thermal evaporation. Among these samples, our study identifies the amorphous Co nanofilm with fine agglomerated Co clusters as the optimal electrocatalyst for NITRR in a neutral medium. The resulting Co-NFs/CP exhibits a remarkable Faradaic efficiency (FENH3) of 91.15 % at - 0.9 V vs RHE, surpassing commercial Co foil (39 %) and Co powder (20 %), despite sharing the same metal composition. Furthermore, during the electrochemical NITRR, the key intermediates on the surface of the Co-NFs/CP catalyst were detected by in situ Fourier-transform infrared (FTIR) spectroscopy, and the possible reaction ways were probed by Density functional theory (DFT) calculations. Theoretical calculations illustrate that the abundant low-coordinate Co atoms of Co-NFs/CP could enhances the adsorption of *NO3 intermediates compared to crystalline Co. Additionally, the amorphous Co structure lowers the energy barrier for the rate-determining step (*NH2→*NH3). This work opens a new avenue for the controllable synthesis of amorphous/low crystallinity metal nano-catalysts for various electrocatalysis reaction applications.

16.
ACS Nano ; 17(4): 3209-3224, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36786415

RESUMEN

The electrochemical coreduction of carbon dioxide (CO2) and nitrogenous species (such as NO3-, NO2-, N2, and NO) for urea synthesis under ambient conditions provides a promising solution to realize carbon/nitrogen neutrality and mitigate environmental pollution. Although an increasing number of studies have made some breakthroughs in electrochemical urea synthesis, the unsatisfactory Faradaic efficiency, low urea yield rate, and ambiguous C-N coupling reaction mechanisms remain the major obstacles to its large-scale applications. In this review, we present the recent progress on electrochemical urea synthesis based on CO2 and nitrogenous species in aqueous solutions under ambient conditions, providing useful guidance and discussion on the rational design of metal nanocatalyst, the understanding of the C-N coupling reaction mechanism, and existing challenges and prospects for electrochemical urea synthesis. We hope that this review can stimulate more insights and inspiration toward the development of electrocatalytic urea synthesis technology.

17.
Infect Dis Ther ; 12(2): 663-675, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36697937

RESUMEN

INTRODUCTION: Severe Coronavirus Disease 2019 (COVID-19) progresses with inflammation and coagulation, due to an overactive complement system. Complement component 5a (C5a) plays a key role in the complement system to trigger a powerful "cytokine and chemokine storm" in viral infection. BDB-001, a recombinant human immunoglobulin G4 (IgG4) that specially binds to C5a, has the potential to inhibit the C5a-triggered cytokine storm in treating COVID-19 patients and other inflammation diseases. Here, we have explored its safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy adults. This trial is registered with http://www.chinadrugtrials.org.cn/(CTR20200429 ). METHODS: Thirty-two enrolled participants were randomized into three single-dose cohorts (2, 4, and 8 mg/kg) and 1 multi-dose cohort (4 mg/kg), and received either BDB-001 or placebo (3:1) double-blindly. The safety and tolerability after administration were evaluated for 21 days for single-dose cohorts and 28 days for the multi-dose cohort. The pharmacokinetics of BDB-001 in plasma and pharmacodynamics as free C5a in plasma were analyzed. RESULTS: The incidence of drug-related adverse events (AEs) was low, and all AEs were mild or moderate: neither AEs ≥ 3 (NCI-Common Terminology Criteria For Adverse Events, CTCAE 5.0) nor serious adverse events (SAEs) were found. The area under the concentration-time curve from time zero to 480 h (AUC0-480h), that from time zero to infinity (AUCinf), and peak plasma concentration ©max) increased dose-dependently from 2 to 8 mg/kg in the single-dose cohorts and were characterized by a nonlinear pharmacokinetics of target-mediated drug disposal (TMDD). The accumulation index by AUC0-tau after five administrations (4 mg/kg) from the multi-dose cohort was 6.42, suggesting an accumulation effect. Furthermore, inhibition of C5a at the plasma level was observed. CONCLUSION: The results of this phase I study supported that BDB-001 is a potent anti-C5a inhibitor with safety, tolerability, and no immunogenicity. TRIAL REGISTRATION NUMBER: CTR20200429.

18.
Int J Biol Macromol ; 205: 274-282, 2022 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-35192902

RESUMEN

Due to the crucial role of gluten network in maintaining the tensile properties of frozen-cooked noodles (FCNs), the underlying mechanism of protective effect of curdlan on FCNs quality during frozen storage was explored from the perspective of aggregation behavior and structure of gluten in this study. The results showed that curdlan weakened the depolymerization behavior of gluten proteins through inhibiting the disruption of disulfide bonds; Curdlan stabilized the secondary structure of gluten proteins by restraining the transformation of compact α-helices to other secondary structures; Atomic force microscope results implied that curdlan inhibited the aggregation of gluten chains; Confocal laser scanning microscopy observation analyzed by AngioTool software indicated that the connectivity and uniformity of gluten network were enhanced because of curdlan. This study may provide more comprehensive theories for the strengthening effect of curdlan on FCNs quality from the perspective of gluten structure and contribute to the quality improvement of FCN in the food technology field.


Asunto(s)
Glútenes , beta-Glucanos , Culinaria , Harina/análisis , Glútenes/química
19.
Lancet Microbe ; 3(3): e193-e202, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35098177

RESUMEN

BACKGROUND: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). METHODS: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 µg, 10 µg, 15 µg, 20 µg, and 25 µg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). FINDINGS: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 µg group, 13 [65%] of 20 in the 10 µg group, 17 [85%] of 20 in the 15 µg group, 19 [95%] of 20 in the 20 µg group, 16 [100%] of 16 in the 25 µg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 µg group, three (15%) of 20 in the 10 µg group, six (30%) of 20 in the 15 µg group, seven (35%) of 20 in the 20 µg group, five (31%) of 16 in the 25 µg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 µg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19. INTERPRETATION: ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale. FUNDING: National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences.


Asunto(s)
COVID-19 , SARS-CoV-2 , Adulto , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , China , Humanos , Inmunogenicidad Vacunal , Inmunoglobulina G , Pandemias/prevención & control , Glicoproteína de la Espiga del Coronavirus , Vacunas Sintéticas , Vacunas de ARNm
20.
Food Chem ; 346: 128908, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33401084

RESUMEN

Curdlan has been applied to weaken the quality deterioration of frozen cooked noodles (FCN) during frozen storage. However, the underlying mechanism is still unclear. In this paper, an A/LKB-F probe was used for texture profile analysis and mercury intrusion was firstly used for analyzing ice crystals state in three dimensions. Meanwhile, a systematic study on the water state was conducted, as well as the freeze-thawed stability of FCN under curdlan intervention during frozen storage. The results showed that 0.5% curdlan significantly (P < 0.05) alleviated the decrement in hardness, chewiness and extension, and enhanced the freeze-thawed stability of FCN. This was closely associated with the fact that the addition of curdlan minimized freezable water content, inhibited water mobility and migration, and raised the homogeneity of ice crystals in FCN. This study provides more comprehensive theories for the strengthening effect of curdlan on FCN quality from the perspective of water state.


Asunto(s)
Almacenamiento de Alimentos/métodos , Agua/química , beta-Glucanos/química , Culinaria , Congelación , Dureza , Mercurio/química
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