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1.
Cell ; 185(22): 4049-4066.e25, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36208623

RESUMO

Blocking PD-1/PD-L1 signaling transforms cancer therapy and is assumed to unleash exhausted tumor-reactive CD8+ T cells in the tumor microenvironment (TME). However, recent studies have also indicated that the systemic tumor-reactive CD8+ T cells may respond to PD-1/PD-L1 immunotherapy. These discrepancies highlight the importance of further defining tumor-specific CD8+ T cell responders to PD-1/PD-L1 blockade. Here, using multiple preclinical tumor models, we revealed that a subset of tumor-specific CD8+ cells in the tumor draining lymph nodes (TdLNs) was not functionally exhausted but exhibited canonical memory characteristics. TdLN-derived tumor-specific memory (TTSM) cells established memory-associated epigenetic program early during tumorigenesis. More importantly, TdLN-TTSM cells exhibited superior anti-tumor therapeutic efficacy after adoptive transfer and were characterized as bona fide responders to PD-1/PD-L1 blockade. These findings highlight that TdLN-TTSM cells could be harnessed to potentiate anti-tumor immunotherapy.


Assuntos
Antígeno B7-H1 , Neoplasias , Humanos , Receptor de Morte Celular Programada 1 , Linfócitos T CD8-Positivos , Inibidores de Checkpoint Imunológico , Microambiente Tumoral , Neoplasias/terapia , Neoplasias/patologia , Linfonodos/patologia
2.
J Immunol ; 211(9): 1418-1425, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37728417

RESUMO

Ever-growing evidence has revealed that group 2 innate lymphoid cells (ILC2s) exhibit pleiotropic effects in antihelminth immunity, allergy, tissue protection, and cancer. Currently, the role of ILC2s in cancer is highly controversial regarding the intricate tumor microenvironment (TME), and the tumor-promoting or antitumor immunological mechanisms of ILC2s remain largely unknown. In this study, we report that dopamine receptor 1 (DRD1) restrains ILC2 activity in the TME. DRD1 deficiency promotes ILC2 activation, which irritates eosinophil recruitment and cytotoxic CD8+ T cell expansion during ongoing malignancy. Consequently, DRD1-deficient mice exhibit delayed tumor growth and reduced tumor progression. Furthermore, fenoldopam, a selective DRD1 agonist, restrains the ILC2 response in the TME and aggravates tumor burden in mice. Taken together, our data elaborate that the DRD1 signal acts as an excitatory rheostat in regulating ILC2-dependent antitumor immunity.

3.
Nano Lett ; 24(22): 6821-6827, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38787786

RESUMO

In the quasi-two-dimensional superconductor NbSe2, the superconducting transition temperature (Tc) is layer-dependent, decreasing by about 60% in the monolayer limit. However, for the extremely anisotropic copper-based high-Tc superconductor Bi2Sr2CaCu2O8+δ (Bi-2212), the Tc of the monolayer is almost identical with that of its bulk counterpart. To clarify the effect of dimensionality on superconductivity, here, we successfully fabricate ultrathin flakes of iron-based high-Tc superconductors CsCa2Fe4As4F2 and CaKFe4As4. It is found that the Tc of monolayer CsCa2Fe4As4F2 (after tuning to the optimal doping by ionic liquid gating) is about 20% lower than that of the bulk crystal, while the Tc of three-layer CaKFe4As4 decreases by 46%, showing a more pronounced dimensional effect than that of CsCa2Fe4As4F2. By carefully examining their anisotropy and the c-axis coherence length, we reveal the general trend and empirical law of the layer-dependent superconductivity in these quasi-two-dimensional superconductors.

4.
Hum Mol Genet ; 31(20): 3504-3520, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-35666215

RESUMO

Mutations in genes encoding subunits of the BAF (BRG1/BRM-associated factor) complex cause various neurodevelopmental diseases. However, the underlying pathophysiology remains largely unknown. Here, we analyzed the function of Brahma-related gene 1 (Brg1), a core ATPase of BAF complexes, in the developing cerebral cortex. Loss of Brg1 causes several morphological defects resembling human malformations of cortical developments (MCDs), including microcephaly, cortical dysplasia, cobblestone lissencephaly and periventricular heterotopia. We demonstrated that neural progenitor cell renewal, neuronal differentiation, neuronal migration, apoptotic cell death, pial basement membrane and apical junctional complexes, which are associated with MCD formation, were impaired after Brg1 deletion. Furthermore, transcriptome profiling indicated that a large number of genes were deregulated. The deregulated genes were closely related to MCD formation, and most of these genes were bound by Brg1. Cumulatively, our study indicates an essential role of Brg1 in cortical development and provides a new possible pathogenesis underlying Brg1-based BAF complex-related neurodevelopmental disorders.


Assuntos
Cromatina , DNA Helicases/metabolismo , Malformações do Desenvolvimento Cortical , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Animais , Humanos , Camundongos
5.
FASEB J ; 37(12): e23314, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37983660

RESUMO

Small extracellular vesicles (sEVs) from adipose-derived stem cells (ADSCs) have gained great attention and have been widely used in cell-free therapies for treating diabetic non-healing wounds in recent years. However, further clinical application of ADSC-sEVs have been limited due to their unsolvable defects, including cumbersome extraction procedure, high cost, low yield, etc. Thus, we urgently need to find one therapeutic reagent that could not only accelerate diabetic wound healing as ADSC-sEVs but also overcome these shortcomings. As the extraction process of adipose tissue-derived sEVs (AT-sEVs) is quite simple and labor saving, we put our focus on the efficiencies of white adipose tissue-derived sEVs (WAT-sEVs) and brown adipose tissue-derived sEVs (BAT-sEVs) in diabetic wound repair. After successfully isolating WAT-sEVs and BAT-sEVs by ultracentrifugation, we thoroughly characterized them and compared their diabetic wound healing capabilities both in vitro and in vivo. According to our study, AT-sEVs possess similar competence in diabetic wound healing as compared with ADSC-sEVs. While the effect of BAT-sEVs is not as stable as WAT-sEVs and ADSC-sEVs, the repair efficiency is also slightly lower than the other two sEVs in some cases. In summary, we are the first to discover that WAT-sEVs show great potential in diabetic wound repair. With advantages that are specific to tissue-derived sEVs (Ti-sEVs) such as time- and cost-saving, high-yield, and simple isolation procedure, we believe WAT-sEVs could serve as a novel reliable cell-free therapy for clinical diabetic wound treatment.


Assuntos
Diabetes Mellitus , Vesículas Extracelulares , Humanos , Cicatrização , Tecido Adiposo Branco , Tecido Adiposo Marrom
6.
Inorg Chem ; 63(18): 8171-8179, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38655575

RESUMO

Although 1,10-phenanthroline has been proven to hold a strong complexing capacity for f-block elements and their derivatives have been applied in many fields, research on more highly or completely rigid phenanthroline ligands is still rare due to the challenging syntheses. Here, we reported three tetradentate ligands 2,9-di(pyridin-2-yl)-1,10-phenanthroline (L1), 12-(pyridin-2-yl)-5,6-dihydroquinolino[8,7b][1,10]phenanthroline (L2), and 5,6,11,12-tetrahydrobenzo[2,1-b:3,4-b']bis([1,10]phenanthroline) (L3) with increasing preorganization on the side chain; among which, L3 is fully preorganized. Their complexation reactions with Eu(III) were systematically investigated by electrospray ionization mass spectrometry (ESI-MS), UV-vis titrations, and single-crystal structures. It is found that all three ligands form only 1:1 M/L complexes with Eu(III). The single-crystal structures revealed that the three ligands hold similar coordination modes, while their stability constants determined by UV-vis titrations were L3 (4.80 ± 0.01) > L2 (4.38 ± 0.01) > L1 (3.88 ± 0.01). This trend is supported not only by the thermodynamic stability of rigid ligands compared to free ligands but also by the conclusion that rigid ligands exhibit faster reaction rates (lower energy barrier) than free ligands kinetically. This work is helpful in providing theoretical guidance for the subsequent development of highly preorganized chelating ligands with strong coordination ability and high selectivity for f-block elements.

7.
Inorg Chem ; 63(6): 3063-3074, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38285631

RESUMO

Phenanthroline diamide ligands have been widely used in the separation of trivalent actinides and lanthanides, but little research has focused on extractants with asymmetrical substitutes. Two novel asymmetrical phenanthroline-based ligands N2,N2,N9-triethyl-N9-tolyl-1,10-phenanthroline-2,9-dicarboxamide (DE-ET-DAPhen) and N2-ethyl-N9,N9-dioctyl-N2-tolyl-1,10-phenanthroline-2,9-dicarboxamide (DO-ET-DAPhen) were first synthesized in this work, whose extraction ability and complexation mechanism to trivalent actinides [An(III)] and lanthanides [Ln(III)] were systematically investigated. The ligands dissolved in n-octanol exhibit good extraction ability and high selectivity toward Am(III) in acidic solutions. The complexation mechanism of the ligands with Ln(III) in solution and solid state was analyzed using slope analysis, 1H NMR spectrometric titration, ESI-MS, and calorimetric titration. It is revealed that the ligands complex with Am(III)/Eu(III) with 1:1 stoichiometry. The stability constant (log ß) of the complexation reaction of Eu(III) with DE-ET-DAPhen determined by UV-vis spectrophotometric and calorimetric titration is higher than that of DO-ET-DAPhen, indicating the stronger complexation ability of DE-ET-DAPhen. Meanwhile, the calorimetric titration results show that the complexation process is exothermic with a decreased entropy. The structures of 1:1 complexes of Eu(III) and Nd(III) with DE-ET-DAPhen were analyzed through single-crystal X-ray diffraction. This work proves that ligands containing asymmetrical functional groups are promising for An(III)/Ln(III) separation, which shows great significance in efficient extractants designed for the spent nuclear fuel reprocessing process.

8.
Epilepsy Behav ; 151: 109636, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38232560

RESUMO

Atypical absence seizures are generalized non-convulsive seizures that often occur in children with cognitive impairment. They are common in refractory epilepsy and have been recognized as one of the hallmarks of developmental epileptic encephalopathies. Notably, pathogenic variants associated with AAS, such as GABRG2, GABRG3, SLC6A1, CACNB4, SCN8A, and SYNGAP1, are also linked to developmental epileptic encephalopathies. Atypical absences differ from typical absences in that they are frequently drug-resistant and the prognosis is dependent on the etiology or related epileptic syndromes. To improve clinicians' understanding of atypical absences and provide novel perspectives for clinical treatment, we have reviewed the electro-clinical characteristics, etiologies, treatment, and prognosis of atypical absences, with a focus on the etiology of advancements in gene variants, shedding light on potential avenues for improved clinical management.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia Tipo Ausência , Epilepsia Generalizada , Humanos , Criança , Epilepsia Tipo Ausência/genética , Epilepsia Tipo Ausência/tratamento farmacológico , Convulsões , Proteínas Ativadoras de ras GTPase/genética , Eletroencefalografia
9.
Environ Res ; 245: 117797, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38052357

RESUMO

Problems associated with the colonization and leakage of invertebrates in the granular activated carbon (GAC) filters of waterworks have received increased attention in recent years. To study the effect of environmental factors and water quality on invertebrate abundances, and the backwash control for minimizing invertebrate abundance. A survey of the invertebrate community of GAC filters was carried out monthly from March 2021 to May 2022. A pilot-scale GAC system established in the laboratory alongside a lake, with a volume of 35.3 L. 45 invertebrate species were detected, and 40 of these were rotifers. Significant variation in abundance was observed among seasons before and after GAC filtration, the average invertebrate abundance in the inlet water was 11.1 times that in the filtrate. The GAC filter contained invertebrates that might be responsible for the large number of organisms in the filtrate. Invertebrate abundance in the GAC filter decreased gradually with the carbon layer depth, which the mean invertebrate abundances were 6,926, 5,232, and 3818 ind./kg in the top layer (TL), middle layer (ML), and bottom layer (BL), respectively. Invertebrate abundance was correlated with water temperature and varied seasonally. Among eight water quality parameters, chlorophyll a (Chla) and the total plate count (TPC) were most significantly correlated with invertebrate abundance. According to the statistical modeling and the optimization process of response surface methodology (RSM). The predicted optimal values were a flow rate of 6.36 L/h, a backwash cycle of 3.26 d, and a backwash intensity of 14.97 L/(m2·s) for a minimum invertebrate abundance of 3013 ind./kg in the GAC filter. To maintain invertebrate abundance within an acceptable range, some of these measures might need to be modified depending on the actual conditions.


Assuntos
Carvão Vegetal , Purificação da Água , Animais , Estações do Ano , Clorofila A , Purificação da Água/métodos , Invertebrados , Filtração/métodos
10.
BMC Public Health ; 24(1): 723, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448849

RESUMO

BACKGROUND: Deep learning (DL), a specialized form of machine learning (ML), is valuable for forecasting survival in various diseases. Its clinical applicability in real-world patients with gastric cancer (GC) has yet to be extensively validated. METHODS: A combined cohort of 11,414 GC patients from the Surveillance, Epidemiology and End Results (SEER) database and 2,846 patients from a Chinese dataset were utilized. The internal validation of different algorithms, including DL model, traditional ML models, and American Joint Committee on Cancer (AJCC) stage model, was conducted by training and testing sets on the SEER database, followed by external validation on the Chinese dataset. The performance of the algorithms was assessed using the area under the receiver operating characteristic curve, decision curve, and calibration curve. RESULTS: DL model demonstrated superior performance in terms of the area under the curve (AUC) at 1, 3, and, 5 years post-surgery across both datasets, surpassing other ML models and AJCC stage model, with AUCs of 0.77, 0.80, and 0.82 in the SEER dataset and 0.77, 0.76, and 0.75 in the Chinese dataset, respectively. Furthermore, decision curve analysis revealed that the DL model yielded greater net gains at 3 years than other ML models and AJCC stage model, and calibration plots at 3 years indicated a favorable level of consistency between the ML and actual observations during external validation. CONCLUSIONS: DL-based model was established to accurately predict the survival rate of postoperative patients with GC.


Assuntos
Aprendizado Profundo , Neoplasias Gástricas , Humanos , Algoritmos , Área Sob a Curva , Povo Asiático , Neoplasias Gástricas/cirurgia , População Norte-Americana
11.
Artigo em Inglês | MEDLINE | ID: mdl-38632039

RESUMO

The mutant strain Halomonas bluephagenesis (TDH4A1B5P) was found to produce PHA under low-salt, non-sterile conditions, but the yield was low. To improve the yield, different nitrogen sources were tested. It was discovered that urea was the most effective nitrogen source for promoting growth during the stable stage, while ammonium sulfate was used during the logarithmic stage. The growth time of H. bluephagenesis (TDH4A1B5P) and its PHA content were significantly prolonged by the presence of sulfate ions. After 64 hr in a 5-L bioreactor supplemented with sulfate ions, the dry cell weight (DCW) of H. bluephagenesis weighed 132 g/L and had a PHA content of 82%. To promote the growth and PHA accumulation of H. bluephagenesis (TDH4A1B5P), a feeding regimen supplemented with nitrogen sources and sulfate ions with ammonium sodium sulfate was established in this study. The DCW was 124 g/L, and the PHA content accounted for 82.3% (w/w) of the DCW, resulting in a PHA yield of 101 g/L in a 30-L bioreactor using the optimized culture strategy. In conclusion, stimulating H. bluephagenesis (TDH4A1B5P) to produce PHA is a feasible and suitable strategy for all H. bluephagenesis.


Assuntos
Reatores Biológicos , Meios de Cultura , Halomonas , Nitrogênio , Poli-Hidroxialcanoatos , Sulfatos , Halomonas/metabolismo , Halomonas/crescimento & desenvolvimento , Halomonas/genética , Sulfatos/metabolismo , Poli-Hidroxialcanoatos/metabolismo , Meios de Cultura/química , Nitrogênio/metabolismo , Sulfato de Amônio/metabolismo , Ureia/metabolismo , Fermentação
12.
Sensors (Basel) ; 24(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38475179

RESUMO

False data injection attacks (FDIAs) on sensor networks involve injecting deceptive or malicious data into the sensor readings that cause decision-makers to make incorrect decisions, leading to serious consequences. With the ever-increasing volume of data in large-scale sensor networks, detecting FDIAs in large-scale sensor networks becomes more challenging. In this paper, we propose a framework for the distributed detection of FDIAs in large-scale sensor networks. By extracting the spatiotemporal correlation information from sensor data, the large-scale sensors are categorized into multiple correlation groups. Within each correlation group, an autoregressive integrated moving average (ARIMA) is built to learn the temporal correlation of cross-correlation, and a consistency criterion is established to identify abnormal sensor nodes. The effectiveness of the proposed detection framework is validated based on a real dataset from the U.S. smart grid and simulated under both the simple FDIA and the stealthy FDIA strategies.

13.
Nano Lett ; 23(6): 2121-2128, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36877932

RESUMO

Two-dimensional (2D) van der Waals heterostructures (VDWHs) containing a charge-density wave (CDW) and superconductivity (SC) have revealed rich tunability in their properties, which provide a new route for optimizing their novel exotic states. The interaction between SC and CDW is critical to its properties; however, understanding this interaction within VDWHs is very limited. A comprehensive in situ study and theoretical calculation on bulk 4Hb-TaSe2 VDWHs consisting of alternately stacking 1T-TaSe2 and 1H-TaSe2 monolayers are investigated under high pressure. Surprisingly, the superconductivity competes with the intralayer and adjacent-layer CDW order in 4Hb-TaSe2, which results in substantially and continually boosted superconductivity under compression. Upon total suppression of the CDW, the superconductivity in the individual layers responds differently to the charge transfer. Our results provide an excellent method to efficiently tune the interplay between SC and CDW in VDWHs and a new avenue for designing materials with tailored properties.

14.
Pol J Pathol ; 75(1): 40-53, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741428

RESUMO

C1q/TNF-related protein-9 (CTRP9) has been reported to play roles in several types of retinal diseases. However, the role and the potential mechanism of CTRP9 in glaucoma are still incompletely understood. The expression of CTRP9 in OGD/R-induced retinal ganglion cells (RGCs) was detected by quantitative real-time polymerase chain reaction and western blot assay. Cell proliferation was identified by cell counting Kit-8 assay. Flow cytometry, enzyme-linked immunosorbent assay and western blot assay were performed to assess cell apoptosis. Unfolded protein response (UPR), endoplasmic reticulum (ER) stress and the AMPK pathway were evaluated by western blot assay. The data showed that the expression of CTRP9 was significantly downregulated in OGD/R-induced 661W cells. OGD/R treatment reduced cell viability, promoted cell apoptosis and activated the UPR and ER stress. The overexpression of CTRP9 reversed the effects of OGD/R on 661W cell viability, apoptosis, the UPR and ER stress, as well as the AMPK pathway. However, Compound C, an inhibitor of AMPK signaling, reversed the protection of CTRP9 overexpression against injury from OGD/R in 661W cells. In summary, the results revealed that CTRP9 abated the apoptosis and UPR of OGD/R-induced RGCs by regulating the AMPK pathway, which may provide a promising target for the treatment of glaucoma.


Assuntos
Proteínas Quinases Ativadas por AMP , Apoptose , Estresse do Retículo Endoplasmático , Células Ganglionares da Retina , Transdução de Sinais , Resposta a Proteínas não Dobradas , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/metabolismo , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Camundongos , Linhagem Celular , Adiponectina/metabolismo , Sobrevivência Celular , Glucose/metabolismo , Glaucoma/metabolismo , Glaucoma/patologia , Glicoproteínas
15.
Environ Manage ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867057

RESUMO

The development of renewable energy has become an important means for the world to cope with climate change, ensure energy security, and protect the ecological environment. Using the panel data of 30 provinces in China from 2013 to 2021, this study used the mediating effect model and the spatial Durbin model (SDM) to explore the mechanism and spatial effects of renewable energy development on China's regional carbon emission reduction. The results show that: (1) Renewable energy development can help to reduce carbon emission intensity. (2) The results of mechanism analysis show that renewable energy development reduces carbon intensity by improving energy structure, promoting industrial structure optimization, and industrial structure upgrading. (3) The development of renewable energy can not only reduce the local carbon intensity but also have a positive spillover effect on the carbon intensity of neighboring regions. (4) Further analysis shows that the long-term effect of renewable energy development on carbon emissions is greater than the short-term effect. At the same time, the heterogeneity analysis shows that compared with the Yellow River basin, the development of renewable energy has a significant carbon emission reduction effect in the Yangtze River Economic Belt region. Energy-rich areas fall into the "resource curse", which makes the carbon emission reduction effect of renewable energy development not significant. This paper has certain reference significance for promoting reasonable decomposition between regions and formulating renewable energy development policies.

16.
Am J Physiol Cell Physiol ; 324(6): C1307-C1319, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37154491

RESUMO

It is a widespread and difficult problem that refractory diabetic wounds have a poor local environment and prolonged inflammatory irritation. Tumor cell-derived exosomes play an important role in the development of tumors, as they can promote tumor cell proliferation, migration, and invasion and enhance tumor cell activity. However, tumor tissue-derived exosomes (Ti-Exos) have been less studied, and it is unclear how they affect wound healing. In this study, we extracted Ti-Exos from human oral squamous carcinoma and paracancerous tissue by ultracentrifugation, size exclusion chromatography, and ultrafiltration and performed exosome characterization. In vitro, the oral squamous cell carcinoma tissue-derived exosomes (OSCC Ti-Exos) promoted the proliferation and migration of endothelial cells, keratinocytes, and fibroblasts. In addition, in vivo experiments showed that the OSCC Ti-Exos accelerated the healing of diabetic wounds and were safe in mice. In contrast, there was no promoting effect of paracancerous tissue-derived exosomes either in vivo or in vitro. In conclusion, OSCC Ti-Exos promoted the healing of diabetic wounds, demonstrated preliminary biosafety in mice, and have promise as therapeutic applications.NEW & NOTEWORTHY Diabetic wound healing has become a public health issue that lacks effective treatment. We collected oral squamous cell carcinoma samples and paracancerous tissue and extracted Ti-Exos for verification. In vitro assays revealed that OSCC Ti-EVs could enhance the proliferation and migration of endothelial cells, keratinocytes, and fibroblasts in diabetic cell model. In vivo assays also verified that OSCC Ti-Exos could promote diabetic wound healing, demonstrated preliminary biosafety in mice, and have promise as therapeutic applications.


Assuntos
Carcinoma de Células Escamosas , Diabetes Mellitus , Exossomos , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Camundongos , Animais , Células Endoteliais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Exossomos/química , Cicatrização , Proliferação de Células
17.
Clin Infect Dis ; 76(3): e336-e341, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35666466

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), especially the Delta and Omicron variants, have been reported to show significant resistance to approved neutralizing monoclonal antibodies (mAbs) and vaccines. We previously identified a mAb named 35B5 that harbors broad neutralization to SARS-CoV-2 VOCs. Herein, we explored the protection efficacy of a 35B5-based nasal spray against SARS-CoV-2 VOCs in a small-scale clinical trial. METHODS: We enrolled 30 healthy volunteers who were nasally administered the modified 35B5 formulation. At 12, 24, 48, and 72 hours after nasal spray, the neutralization efficacy of nasal mucosal samples was assayed with pseudoviruses coated with SARS-CoV-2 spike protein of the wild-type strain or the Alpha, Beta, Delta, or Omicron variants. RESULTS: The nasal mucosal samples collected within 24 hours after nasal spray effectively neutralized SARS-CoV-2 VOCs (including Delta and Omicron). Meanwhile, the protection efficacy was 60% effective and 20% effective at 48 and 72 hours after nasal spray, respectively. CONCLUSIONS: A single nasal spray of 35B5 formation conveys 24-hour effective protection against SARS-CoV-2 VOCs, including the Alpha, Beta, Delta, or Omicron variants. Thus, 35B5 nasal spray might be potential in strengthening SARS-CoV-2 prevention, especially in high-risk populations. CLINICAL TRIALS REGISTRATION: 2022-005-02-KY.


Assuntos
COVID-19 , Humanos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Sprays Nasais , SARS-CoV-2/genética
18.
Small ; 19(38): e2301985, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37226367

RESUMO

Benefiting from the admirable energy density (1086 Wh kg-1 ), overwhelming security, and low environmental impact, rechargeable zinc-air batteries (ZABs) are deemed to be attractive candidates for lithium-ion batteries. The exploration of novel oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) bifunctional catalysts is the key to promoting the development of zinc-air batteries. Transitional metal phosphides (TMPs) especially Fe-based TMPs are deemed to be a rational type of catalyst, however, their catalytic performance still needs to be further improved. Considering Fe (heme) and Cu (copper terminal oxidases) are nature's options for ORR catalysis in many forms of life from bacteria to humans. Herein, a general "in situ etch-adsorption-phosphatization" strategy is designed for the fabrication of hollow FeP/Fe2 P/Cu3 P-N, P codoped carbon (FeP/Cu3 P-NPC) catalyst as the cathode of liquid and flexible ZABs. The liquid ZABs manifest a high peak power density of 158.5 mW cm-2 and outstanding long-term cycling performance (≈1100 cycles at 2 mA cm-2 ). Similarly, the flexible ZABs deliver superior cycling stability of 81 h at 2 mA cm-2 without bending and 26 h with different bending angles.

19.
Small ; 19(25): e2301012, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36932873

RESUMO

Porous metal-organic framework (MOF) liquids with permanent porosity, good fluidity, and fine dispersion attract broad attention in catalysis, transportation, gas storage, and chemical separations. Yet, the design and synthesis of porous MOF liquids for drug delivery remain less explored. Herein, a simple and general strategy is reported to prepare ZIF-91 porous liquid (ZIF-91-PL) via surface modification and ion exchange. The cationic nature of ZIF-91-PL not only renders it antibacterial but also with high curcumin loading capacity and sustained release. More importantly, the acrylate group on the grafted side chain of ZIF-91-PL makes it feasible to crosslink with modified gelatin through light curing, and the obtained hydrogel shows a significantly improved healing effect on the wound of diabetes. This work demonstrates for the first time, a MOF-based porous liquid for drug delivery, and the further fabrication of composite hydrogel may have potential applications in biomedical science.


Assuntos
Diabetes Mellitus , Estruturas Metalorgânicas , Humanos , Porosidade , Estruturas Metalorgânicas/química , Bandagens , Cicatrização , Hidrogéis/farmacologia
20.
Chemistry ; 29(33): e202300456, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37013708

RESUMO

The separation of actinides from lanthanides in spent nuclear fuel reprocessing is a vital step of nuclear fuel cycle process. As one class of mature industrial extractants, the organophosphorus extractants have been widely used for the extraction and separation of actinides and lanthanides in spent fuel reprocessing due to their strong extraction ability and low-cost acquisition. In this concept, the application scope of tributyl phosphate (TBP), bis(2-ethylhexyl) phosphate (HDEHP), octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO), trialkyl phosphine oxide (TRPO), and purified Cyanex 301 (bis(2,4,4-trimethylpentyl) dithiophosphinic acid, HA301) are introduced, and their extraction mechanism, as well as structure-function relationships for separation of actinides over lanthanides are also discussed. Furthermore, the design criteria, extraction properties and mechanism of several typical newly developed organophosphorus extractants (CMPO-modified calixarene/pillarene, phenanthroline-derived organophosphorus extractants, and phosphate-modified carborane) based on pre-organized skeletons are briefly reviewed. Finally, the important role played by those organophosphorus extractants is emphasized and potential applications in separation of actinides over lanthanides in future advanced nuclear fuel cycle are identified.


Assuntos
Elementos da Série Actinoide , Elementos da Série dos Lantanídeos , Óxidos , Fosfatos
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