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1.
Nat Nanotechnol ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750167

RESUMEN

Exploration of new dielectrics with a large capacitive coupling is an essential topic in modern electronics when conventional dielectrics suffer from the leakage issue near the breakdown limit. Here, to address this looming challenge, we demonstrate that rare-earth metal fluorides with extremely low ion migration barriers can generally exhibit an excellent capacitive coupling over 20 µF cm-2 (with an equivalent oxide thickness of ~0.15 nm and a large effective dielectric constant near 30) and great compatibility with scalable device manufacturing processes. Such a static dielectric capability of superionic fluorides is exemplified by MoS2 transistors exhibiting high on/off current ratios over 108, ultralow subthreshold swing of 65 mV dec-1 and ultralow leakage current density of ~10-6 A cm-2. Therefore, the fluoride-gated logic inverters can achieve notably higher static voltage gain values (surpassing ~167) compared with a conventional dielectric. Furthermore, the application of fluoride gating enables the demonstration of NAND, NOR, AND and OR logic circuits with low static energy consumption. In particular, the superconductor-insulator transition at the clean-limit Bi2Sr2CaCu2O8+δ can also be realized through fluoride gating. Our findings highlight fluoride dielectrics as a pioneering platform for advanced electronic applications and for tailoring emergent electronic states in condensed matter.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38750897

RESUMEN

OBJECTIVES: The aim of this study was to characterise the first complete genome of Porphyromonas pogonae strain PP01-1 of human origin in China. METHODS: Illumina NovaSeq 6000 (200X coverage) and Nanopore MinION platform (100X coverage) were used for genome sequencing. The de novo hybrid assembly of short Illumina reads and long MinION reads was performed using Unicycler (v.0.5.0). Genome annotation of PP01-1 was performed using the prokaryotic gene prediction tool Prokka1.14.6.The genome was further analysed using several bioinformatics tools, including ResFinder, VFDB, VirulenceFinder,TYGS, AntiSMASH, PathogenFinder, MobileElementfinder, CRISPRFinder, and IslandViewer. RESULTS: The assembled circular genome of Porphyromonas pogonae strain PP01-1 was 2,916,423 bp in length with a GC content of 41.0%, and no plasmid sequence was detected. A total of 2399 coding sequences were predicted by Prokka. PP01-1 harbors antimicrobial resistance genes blaOXA-347 (beta-lactamase resistance), tet(Q) (tetracycline) and floR (chloramphenicol and florfenicol). CONCLUSION: Here we first report the complete genome of Porphyromonas pogonaestrain PP01-1 of human origin. In this strain, we firstly identified blaOXA-347 and tet(Q) in Porphyromonas pogonae, which will paves the way of further analysis that would aim to identify the potential mechanism of ARGs and virulence factors in Porphyromonas pogonae.

3.
Sci Total Environ ; 935: 173329, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38772482

RESUMEN

The remediation of high-concentration thallium (Tl+) contaminated wastewater is a critical environmental concern. Current research emphasizes the effectiveness of adsorption and oxidation methods for Tl+ treatment, yet challenges persist in enhancing their performance. This study explores the feasibility of emergency Tl+ wastewater treatment and elucidates the mechanisms of Tl+ incorporation into mineral structures, with a focus on the struvite mineral as a framework for Tl+ integration via NH4+ ion exchange. To assess the efficacy and mechanisms of Tl+ immobilization, we utilized comprehensive analytical techniques, including X-ray Diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy with Energy-Dispersive X-ray Spectroscopy (SEM-EDS), Thermogravimetric Analysis (TG), and Density Functional Theory (DFT) calculations. The findings reveal that struvite adsorbs Tl+ onto its surface, followed by an ion exchange process between monovalent cations (NH4+/K+) within the structure and Tl+. Ultimately, Tl+ is incorporated in the form of a (NH4,Tl)MgPO4 solid solution within the structure, achieving a remarkable maximum incorporation capacity of 320.56 mg/g, which significantly surpasses the capacity of typical adsorbents. The findings demonstrate significant Tl+ incorporation, validating the approach for emergency wastewater treatment and suggesting the potential of mineralogy in environmental remediation. This research contributes to advancing heavy metal wastewater treatment strategies, offering a foundation for further investigation.

4.
Nano Lett ; 24(18): 5562-5569, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38682815

RESUMEN

Transition metal trichalcogenides (TMTCs) offer remarkable opportunities for tuning electronic states through modifications in chemical composition, temperature, and pressure. Despite considerable interest in TMTCs, there remain significant knowledge gaps concerning the evolution of their electronic properties under compression. In this study, we employ experimental and theoretical approaches to comprehensively explore the high-pressure behavior of the electronic properties of TiS3, a quasi-one-dimensional (Q1D) semiconductor, across various temperature ranges. Through high-pressure electrical resistance and magnetic measurements at elevated pressures, we uncover a distinctive sequence of phase transitions within TiS3, encompassing a transformation from an insulating state at ambient pressure to the emergence of an incipient superconducting state above 70 GPa. Our findings provide compelling evidence that superconductivity at low temperatures of ∼2.9 K is a fundamental characteristic of TiS3, shedding new light on the intriguing high-pressure electronic properties of TiS3 and underscoring the broader implications of our discoveries for TMTCs in general.

5.
J Hazard Mater ; 469: 134069, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38518693

RESUMEN

Chloramphenicol (CAP) is an antibiotic that commonly pollutes the environment, and microorganisms primarily drive its degradation and transformation. Although several pathways for CAP degradation have been documented in different bacteria, multiple metabolic pathways in the same strain and their potential biological significance have not been revealed. In this study, Sphingobium WTD-1, which was isolated from activated sludge, can completely degrade 100 mg/L CAP within 60 h as the sole energy source. UPLC-HRMS and HPLC analyses showed that three different pathways, including acetylation, hydroxyl oxidation, and oxidation (C1-C2 bond cleavage), are responsible for the metabolism of CAP. Importantly, acetylation and C3 hydroxyl oxidation reduced the cytotoxicity of the substrate to strain WTD-1, and the C1-C2 bond fracture of CAP generated the metabolite p-nitrobenzoic acid (PNBA) to provide energy for its growth. This indicated that the synergistic action of three metabolic pathways caused WTD-1 to be adaptable and able to degrade high concentrations of CAP in the environment. This study deepens our understanding of the microbial degradation pathway of CAP and highlights the biological significance of the synergistic metabolism of antibiotic pollutants by multiple pathways in the same strain.


Asunto(s)
Cloranfenicol , Sphingomonadaceae , Cloranfenicol/metabolismo , Biodegradación Ambiental , Antibacterianos/metabolismo , Redes y Vías Metabólicas , Sphingomonadaceae/metabolismo
6.
Environ Pollut ; 345: 123514, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38346634

RESUMEN

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) is an ozonation product of the rubber antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD). 6PPD-Q has recently been detected in various environmental media, which may enter the human body via inhalation and skin contact pathways. However, the human metabolism of 6PPD-Q has remained unknown. This study investigated the in vitro Cytochrome P450-mediated metabolism of 6PPD-Q in human and rat liver microsomes (HLMs and RLMs). 6PPD-Q was significantly metabolized at lower concentrations but slowed at high concentrations. The intrinsic clearance (CLint) of 6PPD-Q was 21.10 and 18.58 µL min-1 mg-1 protein of HLMs and RLMs, respectively, suggesting low metabolic ability compared with other reported pollutants. Seven metabolites and one intermediate were identified, and metabolites were predicted immunotoxic or mutagenic toxicity. Mono- and di-oxygenation reactions were the main phase I in vitro metabolic pathways. Enzyme inhibition experiments and molecular docking techniques were further used to reveal the metabolic mechanism. CYP1A2, 3A4, and 2C19, especially CYP1A2, play critical roles in 6PPD-Q metabolism in HLMs, whereas 6PPD-Q is extensively metabolized in RLMs. Our study is the first to demonstrate the in vitro metabolic profile of 6PPD-Q in HLMs and RLMs. The results will significantly contribute to future human health management targeting the emerging pollutant 6PPD-Q.


Asunto(s)
Citocromo P-450 CYP1A2 , Microsomas Hepáticos , Fenilendiaminas , Humanos , Ratas , Animales , Citocromo P-450 CYP1A2/metabolismo , Microsomas Hepáticos/metabolismo , Simulación del Acoplamiento Molecular , Sistema Enzimático del Citocromo P-450/metabolismo , Quinonas , Cinética
7.
Fish Shellfish Immunol ; 145: 109353, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38184180

RESUMEN

In the past decade, the outbreak of Streptococcus agalactiae has caused significant economic losses in tilapia farming. Vaccine immunization methods and strategies have gradually evolved from single-mode to multi-mode overall prevention and control strategies. In this study, an inactivated vaccine of S. agalactiae with a chitosan oligosaccharide (COS) adjuvant was constructed using different administration methods: intraperitoneal injection (Ip), immersion combined with intraperitoneal injection (Im + Ip), immersion combined with oral administration (Im + Or), and oral administration (Or). Safety analysis revealed no adverse effects on tilapia, and the vaccine significantly promoted fish growth and development when administered through Im + Or or Or immunization. Following vaccination, innate immunity parameters including SOD, ACP and CAT activities were all significantly enhanced. Additionally, specific serum IgM antibodies reached their highest level at the 6th week post vaccination. Skin and intestinal mucus IgT antibodies reached peaked at the 6th and 7th week post vaccination, respectively. The relative peak expression values for IL-8, IL-12, MHC-I, MHC-II, IgM, IgT, CD4, CD8, TNFα, IFNγ from Im + Ip group were significantly higher than those in Ip group, Im + Or group and Or group in most cases (p < 0.05). Importantly, the relative protection survival of Im + Ip group was the highest (78.6%), followed by the Ip group (71.4%), the Or group (64.3%) and the Im + Or group (57.1%). In summary, this study encourages further research on multi-channel immunization strategies of other kinds of vaccines in other aquatic economic animals to improve their disease resistance.


Asunto(s)
Quitosano , Cíclidos , Enfermedades de los Peces , Infecciones Estreptocócicas , Tilapia , Animales , Streptococcus agalactiae , Vacunas Bacterianas , Vacunación , Inmunidad Innata , Inmunoglobulina M , Oligosacáridos
8.
Cardiol Young ; 34(4): 748-753, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37814585

RESUMEN

BACKGROUND: Early diagnosis of acute coronary syndrome is more and more important because of its mortality and morbidity. Hypertension is one of the pathogenesis of acute coronary syndrome, which often leads to stenosis and ischaemia. Ischaemia-modified albumin is sensitive for the occurrence of ischaemia, which attracted us in the significance of ischaemia-modified albumin in patients with chest pain, especially patients complicated with hypertension. METHODS: In total, 200 patients with acute chest pain were included in the study. According to the diagnostic criteria, patients were divided into acute coronary syndrome group and non-ischaemic chest pain group. Cardiac biomarkers were measured with 30 minutes in emergency department, including cardiac troponin T, creatine kinase MB, and ischaemia-modified albumin. Receiver operating characteristic curve (ROC) analysis was used for the sensitivity and specificity of ischaemia-modified albumin in the early diagnosis of acute coronary syndrome. Comparisons between ischaemia-modified albumin and cardiac Troponin T were done between groups. RESULTS: The demographics in two groups were not significantly different in most aspects. Compared with non-ischaemic chest pain group, serum levels of ischaemia-modified albumin and cardiac Troponin T were significantly higher in acute coronary syndrome group. ROC analysis showed that ischaemia-modified albumin had a good sensitivity and specificity in early diagnosis of acute coronary syndrome. The level of ischaemia-modified albumin in acute coronary syndrome patients with hypertension was higher than that in non-ischaemic chest pain patients. CONCLUSIONS: In patients complained with acute chest pain, the serum measurement of ischaemia-modified albumin is potential valuable for the early diagnosis of acute coronary syndrome, especially combined with ECG. The serum level of ischaemia-modified albumin in acute coronary syndrome patients is significantly associated with hypertension.


Asunto(s)
Síndrome Coronario Agudo , Hipertensión , Albúmina Sérica Humana , Humanos , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/diagnóstico , Troponina T , Biomarcadores , Relevancia Clínica , Albúmina Sérica , Sensibilidad y Especificidad , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Hipertensión/complicaciones , Hipertensión/diagnóstico , Isquemia
9.
Environ Pollut ; 346: 123018, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38016590

RESUMEN

The disposal of coffee shell waste on farmland, is a common practice that can causing the environmental and waste valuable resources. Carbonization has been identified as an effective method for transforming coffee shells into useful products that mitigate environmental pollution. Through the response surface methodology, the carbonization conditions of the coffee shells were optimized and its potential as a biochar-based slow-release urea fertilizer was explored. Experiments were conducted on coffee shell performance under varying carbonization conditions such as temperature (600-1000 °C), time (1-5 h), and heating rate (5-20 °C/min). The results indicated that the ideal urea adsorption was 56.3 mg/g, achieved under carbonization conditions of 2.83 h, 809 °C, and 15.3 °C/min. The optimal nutrient release rate within seven days was 45.4% under carbonization conditions of 3.19 h, 813 °C, and 15.0 °C/min. The infrared spectroscopy analysis indicates that carbonization conditions influenced the absorption peak intensity of coffee shell biochar, while the functional group types remain unchanged. The biochar exhibits diverse functional groups and abundant pores, making it a promising candidate for use as a biochar-based fertilizer material. Overall, the findings demonstrate an effective waste management approach that significantly reduces environmental pollutants while remediating pollution.


Asunto(s)
Café , Restauración y Remediación Ambiental , Fertilizantes , Carbón Orgánico/química , Adsorción , Urea/química
10.
Sci Total Environ ; 912: 168723, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38008322

RESUMEN

2,4-Dichlorophenol, which is largely employed in herbicides and industrial production, is frequently detected in ecosystems and poses risks to human health and environmental safety. Microbial communities are thought to perform better than individual strains in the complete degradation of organic contaminants. However, the synergistic degradation mechanisms of the microbial consortia involved in 2,4-dichlorophenol degradation are still not widely understood. In this study, a bacterial consortium named DCP-2 that is capable of degrading 2,4-dichlorophenol was obtained. Metagenomic analysis, cultivation-dependent functional verification, and co-occurrence network analysis were combined to reveal the primary 2,4-dichlorophenol degraders and the cooperation patterns in the consortium DCP-2. Metagenomic analysis showed that Pseudomonas, Achromobacter, and Pigmentiphaga were the primary degraders for the complete degradation of 2,4-dichlorophenol. Thirty-nine phylogenetically diverse bacterial genera, such as Brucella, Acinetobacter, Aeromonas, Allochromatium and Bosea, were identified as keystone taxa for 2,4-dichlorophenol degradation by keystone taxa analysis of the co-occurrence networks. In addition, a stable synthetic consortium of isolates from DCP-2 was constructed, consisting of Pseudomonas sp. DD-13 and Brucella sp. FZ-1; this synthetic consortium showed superior degradation capability for 2,4-dichlorophenol in both mineral salt medium and wastewater compared with monoculture. The findings provide valuable insights into the practical bioremediation of 2,4-dichlorophenol-contaminated sites.


Asunto(s)
Clorofenoles , Microbiota , Humanos , Bacterias/metabolismo , Clorofenoles/metabolismo , Biodegradación Ambiental , Consorcios Microbianos
11.
J Hazard Mater ; 465: 133348, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38154177

RESUMEN

Chloramphenicols (CAPs) are ubiquitous emerging pollutants that threaten ecological environments and human health. Microbial and enzyme-based biodegradation strategies offer a cost-effective environmentally friendly approach for CAPs removal from contaminated sites. Here, CpmO, a novel multifunctional oxidase for CAP degradation was identified from the CAP-degrading strain Sphingobium sp. WTD-1. This enzyme was found to be responsible for both the oxidation of the C3-hydroxyl and oxidative cleavage of the C1-C2 bond of CAP, and the oxidative cleavage pathway of CAP was dominant. The catalytic efficiency of CpmO for CAP was 41.6 times that for thiamphenicol (TAP) under the optimal conditions (40 °C, pH 6.0). CpmO was identified as a member of the glucose-methanol-choline oxidoreductase family. Molecular docking and site-directed mutagenesis analysis indicated that CAP was connected to the key amino acid residues E231/E395, K277, and I273/A276 in CpmO through hydrogen bonding, nonclassical hydrogen bonding, and π-π stacking forces, respectively. The catalytic activities of the A276W, K277P, and E231S mutants were found to be 1.1 times, 6.4 times, and 13.2 times higher than that of the wild type, respectively. These findings provide genetic resources and theoretical guidance for future application in biotechnological and metabolic engineering efforts for the remediation of CAPs-contaminated environments.


Asunto(s)
Cloranfenicol , Oxidorreductasas , Humanos , Sitios de Unión/genética , Simulación del Acoplamiento Molecular , Mutagénesis Sitio-Dirigida
12.
J Org Chem ; 88(23): 16581-16588, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37976463

RESUMEN

An iron-catalyzed efficient C-H amination for the construction of imidazole-fused-ring systems was developed under aerobic conditions. Compared to previous studies, this work exhibited green features. The reaction was conducted in the green solvent anisole, with water as the only byproduct. Four C(sp3)-H bonds were cleaved and three C-N bonds were formed in this transformation. Imidazo[1,5-a]pyridine-, imidazo[5,1-b]oxazole-, imidazo[5,1-b]thiazole-, imidazo[1,5-a]pyrazine-, and imidazo[1,5-a]imidazole-related N-heterocycles were obtained in acceptable-to-excellent yield.

13.
Nano Lett ; 23(22): 10282-10289, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37906179

RESUMEN

Quasiparticles consisting of correlated electron(s) and hole(s), such as excitons and trions, play important roles in the optical phenomena of van der Waals semiconductors and serve as unique platforms for studies of many-body physics. Herein, we report a gate-tunable exciton-to-trion transition in pressurized monolayer MoSe2, in which the electronic band structures are modulated continuously within a diamond anvil cell. The emission energies of both the exciton and trion undergo large blueshifts over 90 meV with increasing pressure. Surprisingly, the trion binding energy remains constant at 30 meV, regardless of the applied pressure. Combining ab initio density functional theory calculations and quantum Monte Carlo simulations, we find that the remarkable robustness of the trion binding energy originates from the spatially diffused nature of the trion wave function and the weak correlation between its constituent electron-hole pairs. Our findings shed light on the optical properties of correlated excitonic quasiparticles in low-dimensional materials.

14.
Materials (Basel) ; 16(18)2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37763441

RESUMEN

Si3N4 ceramic as a tool material shows promising application prospects in high-speed machining fields; however, the required high mechanical properties and low-cost preparation of Si3N4 ceramic tool materials restrict its application. Herein, synergistic reinforced Si3N4 ceramic tool materials were fabricated by adding ß-Si3N4 seeds, inexpensive Si3N4 whiskers and TiC particles into coarse commercial Si3N4 powder (D50 = 1.5 µm), then sintering by hot-pressing with low temperature and short holding time (1600 °C-30 min-40 MPa). The phase assemblage, microstructure evolution and toughening mechanisms were investigated. The results reveal that the sintered Si3N4 ceramics with synergistic reinforcement, compared to those with individual reinforcement, present an enhancement in relative density (from 94.92% to 97.15%), flexural strength (from 467.56 ± 36.48 to 809.10 ± 45.59 MPa), and fracture toughness (from 8.38 ± 0.19 to 10.67 ± 0.16 MPa·m1/2), as well as a fine Vickers hardness of 16.86 ± 0.19 GPa. Additionally, the various reinforcement modes of Si3N4 ceramics including intergranular fracture, crack deflection, crack bridging and whiskers extraction were observed in crack propagation, arising from the contributions of the added ß-Si3N4 seeds, Si3N4 whiskers and TiC particles. This work is expected to serve as a reference for the production of ceramic cutting tools.

15.
Sci Adv ; 9(36): eadf6758, 2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37683003

RESUMEN

Two-dimensional superconductivity is primarily realized in atomically thin layers through extreme exfoliation, epitaxial growth, or interfacial gating. Apart from their technical challenges, these approaches lack sufficient control over the Fermiology of superconducting systems. Here, we offer a Fermiology-engineering approach, allowing us to desirably tune the coherence length of Cooper pairs and the dimensionality of superconducting states in arsenic phosphides AsxP1-x under hydrostatic pressure. We demonstrate how this turns these compounds into tunable two-dimensional superconductors with a dome-shaped phase diagram even in the bulk limit. This peculiar behavior is shown to result from an unconventional valley-dimensionality locking mechanism, driven by a delicate competition between three-dimensional hole-type and two-dimensional electron-type energy pockets spatially separated in momentum space. The resulting dimensionality crossover is further discussed to be systematically controllable by pressure and stoichiometry tuning. Our findings pave a unique way to realize and control superconducting phases with special pairing and dimensional orders.

16.
Nat Commun ; 14(1): 5568, 2023 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-37689758

RESUMEN

Van der Waals dielectrics are fundamental materials for condensed matter physics and advanced electronic applications. Most dielectrics host isotropic structures in crystalline or amorphous forms, and only a few studies have considered the role of anisotropic crystal symmetry in dielectrics as a delicate way to tune electronic properties of channel materials. Here, we demonstrate a layered anisotropic dielectric, SiP2, with non-symmorphic twofold-rotational C2 symmetry as a gate medium which can break the original threefold-rotational C3 symmetry of MoS2 to achieve unexpected linearly-polarized photoluminescence and anisotropic second harmonic generation at SiP2/MoS2 interfaces. In contrast to the isotropic behavior of pristine MoS2, a large conductance anisotropy with an anisotropy index up to 1000 can be achieved and modulated in SiP2-gated MoS2 transistors. Theoretical calculations reveal that the anisotropic moiré potential at such interfaces is responsible for the giant anisotropic conductance and optical response. Our results provide a strategy for generating exotic functionalities at dielectric/semiconductor interfaces via symmetry engineering.

17.
J Immunol ; 211(7): 1154-1166, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37610222

RESUMEN

Chronic graft-versus-host disease (cGVHD) involves multiple organs, but little is known about bone marrow (BM) alterations caused by cGVHD. In mice and humans, we found that cGVHD is associated with BM fibrosis resulting in T cell infiltration, IgG deposition, and hematopoietic dysfunction. Macrophages and Nestin+ mesenchymal stromal cells (MSCs) participated in the process of BM fibrosis during BM cGVHD development. BM macrophage numbers were significantly increased in mice and humans with BM fibrosis associated with cGVHD. Amplified macrophages produced TGF-ß1, which recruited Nestin+ MSCs forming clusters, and Nestin+ MSCs later differentiated into fibroblasts, a process mediated by increased TGF-ß/Smad signaling. TLR4/MyD88-mediated activation of endoplasmic reticulum (ER) stress in macrophages is associated with fibrosis by increasing Nestin+ MSC migration and differentiation into fibroblasts. Depletion of macrophages by clodronate-containing liposomes and inhibition of ER stress by 4-phenylbutyric acid reversed BM fibrosis by inhibiting fibroblast differentiation. These studies provide insights into the pathogenesis of BM fibrosis during cGVHD development.


Asunto(s)
Síndrome de Bronquiolitis Obliterante , Células Madre Mesenquimatosas , Humanos , Animales , Ratones , Médula Ósea , Nestina , Macrófagos
18.
PLoS One ; 18(8): e0289970, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37611031

RESUMEN

The blood brain barrier (BBB) efficiently limits the penetration of biologics drugs from blood to brain. Establishment of an in vitro BBB model can facilitate screening of central nervous system (CNS) drug candidates and accelerate CNS drug development. Despite many established in vitro models, their application to biologics drug selection has been limited. Here, we report the evaluation of in vitro transcytosis of anti-human transferrin receptor (TfR) antibodies across human, cynomolgus and mouse species. We first evaluated human models including human cerebral microvascular endothelial cell line hCMEC/D3 and human colon epithelial cell line Caco-2 models. hCMEC/D3 model displayed low trans-epithelial electrical resistance (TEER), strong paracellular transport, and similar transcytosis of anti-TfR and control antibodies. In contrast, the Caco-2 model displayed high TEER value and low paracellular transport. Anti-hTfR antibodies demonstrated up to 70-fold better transcytosis compared to control IgG. Transcytosis of anti-hTfR.B1 antibody in Caco-2 model was dose-dependent and saturated at 3 µg/mL. Enhanced transcytosis of anti-hTfR.B1 was also observed in a monkey brain endothelial cell based (MBT) model. Importantly, anti-hTfR.B1 showed relatively high brain radioactivity concentration in a non-human primate positron emission tomography study indicating that the in vitro transcytosis from both Caco-2 and MBT models aligns with in vivo brain exposure. Typically, brain exposure of CNS targeted biologics is evaluated in mice. However, antibodies, such as the anti-human TfR antibodies, do not cross-react with the mouse target. Therefore, validation of a mouse in vitro transcytosis model is needed to better understand the in vitro in vivo correlation. Here, we performed transcytosis of anti-mouse TfR antibodies in mouse brain endothelial cell-based models, bEnd3 and the murine intestinal epithelial cell line mIEC. There is a good correlation between in vitro transcytosis of anti-mTfR antibodies and bispecifics in mIEC model and their mouse brain uptake. These data strengthen our confidence in the predictive power of the in vitro transcytosis models. Both mouse and human in vitro models will serve as important screening assays for brain targeted biologics selection in CNS drug development.


Asunto(s)
Productos Biológicos , Animales , Ratones , Humanos , Células CACO-2 , Tomografía Computarizada por Rayos X , Encéfalo , Transcitosis
19.
Artículo en Chino | MEDLINE | ID: mdl-37640992

RESUMEN

Objective:To investigate the clinical efficacy and safety of transcervical non-inflatable endoscopic thyroidectomy through the posterior inferior sternocleidomastoid approach. Methods:From December 2022 to May 2023, the clinical data of 35 patients with papillary thyroid carcinoma treated by transcervical non-inflatable endoscopic surgery via posterior inferior sternocleidomastoid approach were retrospectively analyzed. There were 14 males and 21 females, with an average age of 44.7 years. The operation time, bleeding volume, postoperative recovery, complications and follow-up were recorded. Results:All 35 patients successfully completed the surgery, with an average operation time of 4 hours and 7 minutes, an average bleeding volume of 14 ml, and an average postoperative hospital stay of 3.5 days. There were no serious complications and no obvious neck discomfort during postoperative follow-up. Conclusion:Transcervical non-inflatable endoscopic thyroidectomy via posterior inferior sternocleidomastoid approach is safe and effective, with fast postoperative recovery,high appearance satisfaction and good neck comfort.


Asunto(s)
Cuello , Neoplasias de la Tiroides , Femenino , Masculino , Humanos , Adulto , Estudios Retrospectivos , Músculos del Cuello/cirugía , Neoplasias de la Tiroides/cirugía
20.
Org Biomol Chem ; 21(29): 5985-5989, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37435618

RESUMEN

A convenient method for the alkylation of 3-arylbenzo[d]isoxazoles with maleimides under redox-neutral conditions has been developed, giving a series of substituted succinimides in up to 99% yield. This transformation is highly selective to give succinimides, and Heck-type products are successfully avoided. This protocol features 100% atom-economy and broad substrate tolerance, and provides a novel strategy for the synthesis of diverse succinimides and an opportunity for the succinylation of protein medication and for pharmacologists to discover first-in-class drugs.

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