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1.
Materials (Basel) ; 17(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38893902

ABSTRACT

In this study, a top-down approach was employed for the fabrication of flame-retardant wood aerogels. The process involved the removal of lignin and the removal of hemicellulose utilizing NaOH concomitantly with the incorporation of ZnO and urea. Subsequently, an in situ reaction with boric acid was conducted to prepare flame-retardant wood aerogels. The morphology, chemical composition, thermal stability, and flame retardancy of the samples were studied. The results show that the NaOH treatment transformed the wood into a layered structure, and flame-retardant particles were uniformly distributed on the surface of the aerogel. The peak heat release rate (PHRR) and total heat release (THR) of the flame-retardant aerogel were significantly reduced compared with the control samples. Meanwhile, its vertical burning test (UL-94) rating reached the V-0 level, and the Limiting Oxygen Index (LOI) could exceed 90%. The flame-retardant wood aerogel exhibited excellent flame retardancy and self-extinguishing properties.

2.
Int J Biol Macromol ; 256(Pt 2): 128506, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38040143

ABSTRACT

Hansen solubility parameters (HSPs) play a critical role in the majority of processes involving lignin depolymerization, separation, fractionation, and polymer blending, which are directly related to dissolution properties. However, the calculation of lignin HSPs is highly complicated due to the diversity of sources and the complexity of lignin structures. Despite their important role, lignin HSPs have been undervalued, attracting insufficient attention. This review summarizes the calculation methods for lignin HSPs and proposes a straightforward method based on lignin subunits. Furthermore, it highlights the crucial applications of lignin HSPs, such as identifying ideal solvents for lignin dissolution, selecting suitable solvents for lignin depolymerization and extraction, designing green solvents for lignin fractionation, and guiding the preparation of lignin-based composites. For instance, leveraging HSPs to design a series of solvents could potentially achieve sequential controllable lignin fractionation, addressing issues of low value-added applications of lignin resulting from poor homogeneity. Notably, HSPs serve as valuable tools for understanding the dissolution behavior of lignin. Consequently, we expect this review to be of great interest to researchers specializing in lignin and other macromolecules.


Subject(s)
Lignin , Polymers , Lignin/chemistry , Solubility , Solvents/chemistry , Chemical Fractionation
3.
Antimicrob Agents Chemother ; 67(6): e0000823, 2023 06 15.
Article in English | MEDLINE | ID: mdl-37212658

ABSTRACT

In humans, nematode infections are prevalent in developing countries, causing long-term ill health, particularly in children. Worldwide, nematode infections are prevalent in livestock and pets, affecting productivity and health. Anthelmintic drugs are the primary means of controlling nematodes, but there is now high prevalence of anthelmintic resistance, requiring urgent identification of new molecular targets for anthelmintics with novel mechanisms of action. Here, we identified orthologous genes for phosphoethanolamine methyltransferases (PMTs) in nematodes within the families Trichostrongylidae, Dictyocaulidae, Chabertiidae, Ancylostomatoidea, and Ascarididae. We characterized these putative PMTs and found that they possess bona fide PMT catalytic activities. By complementing a mutant yeast strain lacking the ability to synthesize phosphatidylcholine, the PMTs were validated to catalyze the biosynthesis of phosphatidylcholine. Using an in vitro phosphoethanolamine methyltransferase assay with PMTs as enzymes, we identified compounds with cross-inhibitory effects against the PMTs. Corroboratively, treatment of PMT-complemented yeast with the PMT inhibitors blocked growth of the yeast, underscoring the essential role of the PMTs in phosphatidylcholine synthesis. Fifteen of the inhibitors with the highest activity against complemented yeast were tested against Haemonchus contortus using larval development and motility assays. Among them, four were found to possess potent anthelmintic activity against both multiple drug-resistant and susceptible isolates of H. contortus, with IC50 values (95% confidence interval) of 4.30 µM (2.15-8.28), 4.46 µM (3.22-6.16), 28.7 µM (17.3-49.5), and 0.65 µM (0.21-1.88). Taken together, we have validated a molecular target conserved in a broad range of nematodes and identified its inhibitors that possess potent in vitro anthelmintic activity.


Subject(s)
Anthelmintics , Haemonchus , Nematoda , Nematode Infections , Animals , Child , Humans , Saccharomyces cerevisiae/genetics , Anthelmintics/pharmacology , Methyltransferases/genetics , Haemonchus/genetics , Phosphatidylcholines
4.
MAbs ; 15(1): 2185924, 2023.
Article in English | MEDLINE | ID: mdl-36880643

ABSTRACT

Large-molecule antibody biologics have revolutionized medicine owing to their superior target specificity, pharmacokinetic and pharmacodynamic properties, safety and toxicity profiles, and amenability to versatile engineering. In this review, we focus on preclinical antibody developability, including its definition, scope, and key activities from hit to lead optimization and selection. This includes generation, computational and in silico approaches, molecular engineering, production, analytical and biophysical characterization, stability and forced degradation studies, and process and formulation assessments. More recently, it is apparent these activities not only affect lead selection and manufacturability, but ultimately correlate with clinical progression and success. Emerging developability workflows and strategies are explored as part of a blueprint for developability success that includes an overview of the four major molecular properties that affect all developability outcomes: 1) conformational, 2) chemical, 3) colloidal, and 4) other interactions. We also examine risk assessment and mitigation strategies that increase the likelihood of success for moving the right candidate into the clinic.


Subject(s)
Biological Products , Biological Products/therapeutic use , Antibodies , Risk Assessment , Workflow
5.
Org Lett ; 25(10): 1605-1610, 2023 Mar 17.
Article in English | MEDLINE | ID: mdl-36602376

ABSTRACT

Incorporating two pyrrole subunits at the bay positions of perylene-diimide has been a long-pursued goal since 2009, but it has not been achieved due to high strain. Herein, via one step Buchwald-Hartwig reaction, PDI-2N was successfully generated with a bowl depth of 1.52 Å. Though with electron-rich pyrrole embedding, PDI-2N's radical anion and dianion were facilely prepared and were investigated both experimentally and theoretically. Moreover, PDI-2N crystallized in different manners under distinct conditions, and it formed tubular crystals with infinite two-directional columnar stacking under DMF conditions. This finding develops a dream bowl-shaped PDI derivative that holds great promise in organoelectronics.

6.
J Phys Chem Lett ; 14(3): 798-808, 2023 Jan 26.
Article in English | MEDLINE | ID: mdl-36652698

ABSTRACT

Using first-principles calculations in combination with nonadiabatic molecular dynamics (NAMD), we propose novel heterostructures of carbon nitride (C7N6) and the Janus GaSnPS monolayer as promising direct Z-scheme photocatalysts for solar-driven overall water splitting. The out-of-plane electric field due to the electric polarization which is dependent on the stacking pattern alters the band alignment and catalytic activity of the heterostructures. The relatively strong interfacial nonadiabatic coupling and long quantum coherence time accelerate the interlayer carrier recombination, enabling a direct Z-scheme photocatalytic mechanism. More importantly, the redox ability of the remanent photogenerated carriers in the Z scheme is strong enough to trigger both the hydrogen evolution reaction (HER) and oxygen reduction reaction (OER) simultaneously without the help of sacrificial agents. Our work reveals a fundamental understanding of ultrafast charge carrier dynamics at vdW heterointerfaces as well as new design prospects for highly efficient direct Z-scheme photocatalysts.

7.
Sci Rep ; 12(1): 19136, 2022 11 09.
Article in English | MEDLINE | ID: mdl-36352251

ABSTRACT

Lignin is a natural and renewable aromatic polymer, but only about 2% of lignin is utilized with high added value. Polydispersity and heterogeneity are the key reasons for the difficulty in separation, fractionation, characterization, purification and utilization of lignin. However, the molecular weight of lignin is still described from the overall perspective of number-/weight-average molecular weight (Mn and Mw), which if far from enough to understand the heterogeneous and dispersed lignin. To provide a tool for understanding the molecular weight of lignin from a molecular perspective, an integral method for quantifying the molecular characteristics of lignin molecules at arbitrary molecular intervals on the molecular weight distribution curve of lignin was established. The molecular contents of wheat straw lignin as well as its soluble and insoluble fractions at different intervals were calculated. The ease of fractionation of small molecules with weights lower than 8000 g/mol into soluble fractions, and that of large molecules with weights higher than 10,000 g/mol into insoluble fractions were quantitatively analyzed. The established integral method will significantly help in the understanding the properties of lignin at the molecular-level, as well as the fractionation and utilization of lignin.


Subject(s)
Chemical Fractionation , Lignin , Chemical Fractionation/methods , Triticum , Molecular Weight
8.
Int J Parasitol Parasites Wildl ; 19: 89-95, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36090665

ABSTRACT

Avian malaria, caused by Plasmodium spp. and transmitted by mosquitos, is a leading cause of mortality of captive penguins. Antimalarial drugs are currently used to control infections in penguins. However, the effectiveness of treatment reduces significantly by the time the clinical signs appear, while early and unnecessary treatment interferes with development of protective immunity. Therefore, for suppressing parasitemia without affecting the development of immunity in captive penguins, antimalaria drugs need to be administered at the right time, which requires reliable diagnostic tools that can determine the levels of circulating antimalaria antibodies. In the present study, we have developed an enzyme-linked immunosorbent assay (ELISA) diagnostic assay based on the merozoite surface protein 1 (MSP-1) of P. relictum isolate SGS1 to specifically detect and relatively quantify antimalaria antibodies in penguins. We expressed and purified a truncated P. relictum isolate SGS1 MSP-1 and optimized its biotinylation and subsequent conjugation to streptavidin alkaline phosphatase for signal generation in ELISA. We tested the assay by analyzing sera obtained from penguins at the Baltimore Zoo, from Spring through Fall, and found that levels of detectable antibodies against MSP-1 varied seasonally for individual penguins, consistent with the expected seasonal variations in avian malaria prevalence. Corroboratively, we analyzed the sensitivity of the assay by titrating positive sera and found that the signal intensity generated was serum concentration-dependent, thus validating the ability of the assay to detect and relatively quantify the levels of antimalaria antibodies in penguin sera.

9.
Lab Invest ; 102(11): 1225-1235, 2022 11.
Article in English | MEDLINE | ID: mdl-35804043

ABSTRACT

Glaucoma, a common cause of blindness, is characterized by the progressive loss of retinal ganglion cells (RGCs). Growing evidence suggests that nobiletin (NOB) is a promising neuroprotective drug; however, its effects on glaucomatous neurodegeneration remain unknown. Using rat models of microbead occlusion in vivo and primary RGCs model of hypoxia in vitro, we first demonstrate that NOB reduces RGC apoptosis by a TUNEL assay, Hoechst 33342 staining and FluoroGold (FG) retrograde labeling. This effect does not depend on intraocular pressure (IOP) lowering. Additionally, NOB partially restored the functional and structural damage of inner retinas, attenuated Müller glial activation and oxidative stress caused by ocular hypertension. At 2 weeks after IOP elevation, NOB further enhanced Nrf2/HO-1 pathway in RGCs to withstand the cumulative damage of ocular hypertension. With the administration of HO-1 inhibitor tin-protoporphyrin IX (SnPP), the protective effect of NOB was attenuated. Overall, these results indicate that NOB exerts an outstanding neuroprotective effect on RGCs of glaucomatous neurodegeneration. Besides, interventions to enhance activation of Nrf2/HO-1 pathway can slow the loss of RGCs and are viable therapies for glaucoma.


Subject(s)
Glaucoma , Neuroprotective Agents , Ocular Hypertension , Rats , Animals , Retinal Ganglion Cells , NF-E2-Related Factor 2/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/metabolism , Disease Models, Animal , Ocular Hypertension/drug therapy , Ocular Hypertension/metabolism , Glaucoma/drug therapy , Glaucoma/metabolism , Hypoxia/metabolism
10.
Nanomaterials (Basel) ; 12(12)2022 Jun 08.
Article in English | MEDLINE | ID: mdl-35745308

ABSTRACT

A humidity sensor is a crucial device in daily life; therefore, in the present study, a novel humidity sensor was designed to increase its specific surface area to improve its humid sensing capacity and conductivity. Titanium dioxide nanoparticles (TiNP) consisting of zero-dimensional nanospheres and one-dimensional nanotubes were prepared by anodic oxidation. Rod-shaped cellulose nanocrystals (CNCs) with average length and diameter of 60 nm and 800 nm, respectively, were obtained by enzymatic hydrolysis and high pressure homogenization. TiNP/CNC composite films exhibited superior hydrophilicity and large specific surface areas based on Fourier transform infrared spectroscopy and nitrogen adsorption-desorption results. The humidity sensing characteristics of sensors based on TiNP/CNC flexible composite films with varying contents of TiNP were investigated under a relative humidity range of 11-97%. The 6% TiNP/CNC-based humidity sensor exhibited high humidity response, rapid response/recovery speed, and high stability. Furthermore, the humidity sensing mechanism of TiNP/CNC composite films was analyzed based on the density functional theory. TiNP/CNC-based humidity sensors could be applied in flexible and wearable electronics.

11.
ACS Nano ; 16(6): 8751-8765, 2022 06 28.
Article in English | MEDLINE | ID: mdl-35579595

ABSTRACT

Hard-to-transfect cells are cells that are known to present special difficulties in intracellular delivery of exogenous entities. However, the special transport behaviors underlying the special delivery problem in these cells have so far not been examined carefully. Here, we combine single-particle motion analysis, cell biology studies, and mathematical modeling to investigate nanoparticle transport in bone marrow-derived mesenchymal stem cells (BMSCs), a technologically important type of hard-to-transfect cells. Tat peptide-conjugated quantum dots (QDs-Tat) were used as the model nanoparticles. Two different yet complementary single-particle methods, namely, pair-correlation function and single-particle tracking, were conducted on the same cell samples and on the same viewing stage of a confocal microscope. Our results reveal significant differences in each individual step of transport of QDs-Tat in BMSCs vs a commonly used model cell line, HeLa cells. Single-particle motion analysis demonstrates that vesicle escape and cytoplasmic diffusion are dramatically more difficult in BMSCs than in HeLa cells. Cell biology studies show that BMSCs use different biological pathways for the cellular uptake, vesicular transport, and exocytosis of QDs-Tat than HeLa cells. A reaction-diffusion-advection model is employed to mathematically integrate the individual steps of cellular transport and can be used to predict and design nanoparticle delivery in BMSCs. This work provides dissective, quantitative, and mechanistic understandings of nanoparticle transport in BMSCs. The investigative methods described in this work can help to guide the tailored design of nanoparticle-based delivery in specific types and subtypes of hard-to-transfect cells.


Subject(s)
Nanoparticles , Quantum Dots , Humans , HeLa Cells , Peptides , Biological Transport
12.
Neuroscience ; 490: 89-99, 2022 05 10.
Article in English | MEDLINE | ID: mdl-35257794

ABSTRACT

Glaucoma is a neurodegenerative disease characterized by progressive retinal ganglion cell (RGC) death. Recently, many studies have reported that the N-methyl D-aspartate receptor 2B (NR2B) subunit is excitotoxic in the pathogenesis of glaucoma, but the molecular mechanism should be further explored. In our present study, we investigated the involvement of the NR2B-postsynaptic density protein-95 (PSD95) complex in RGC apoptosis in an experimental glaucoma animal model and determined whether inhibition of the NR2B-PSD95 interaction protected RGCs. We found that levels of NR2B, phosphorylated NR2B (p-NR2B) and PSD95 were significantly increased after 12 h of reperfusion, and the protein expression levels were maintained after 24 h of reperfusion in the ischemia-reperfusion (I/R) injury model. Immunohistochemical staining showed that NR2B and PSD95 partially colocalized in the ganglion cell layer (GCL). Increased levels of NR2B and p-NR2B were also detected in the rat chronic ocular hypertension (COH) model, while decreased PSD95 levels accompanied by severe injury were observed. Tat-NR2B9c treatment significantly increased RGC survival in the I/R injury model by disrupting the NR2B-PSD95 interaction, as confirmed by Brn3A fluorescent labelling and TdT-mediated dUTP nick-end labelling (TUNEL) assays. Levels of the apoptosis-related proteins Bax and cleaved caspase-3 decreased as the number of surviving RGCs increased. Together, our results suggest that the NR2B-PSD95 complex was involved in RGC death in the retinal I/R injury model. Tat-NR2B9c exerted a neuroprotective effect on RGC survival in the retinal I/R injury model by disrupting the NR2B-PSD95 interaction.


Subject(s)
Disks Large Homolog 4 Protein , Glaucoma , Neurodegenerative Diseases , Neuroprotective Agents , Receptors, N-Methyl-D-Aspartate , Reperfusion Injury , Animals , Apoptosis , Apoptosis Regulatory Proteins/metabolism , Disease Models, Animal , Disks Large Homolog 4 Protein/genetics , Glaucoma/metabolism , Neurodegenerative Diseases/metabolism , Neuroprotective Agents/pharmacology , Rats , Receptors, N-Methyl-D-Aspartate/genetics , Reperfusion Injury/metabolism , Retina/metabolism
13.
Front Microbiol ; 12: 800293, 2021.
Article in English | MEDLINE | ID: mdl-35046922

ABSTRACT

Cryptosporidium parvum is a highly prevalent protozoan parasite that causes a diarrheal disease in humans and animals worldwide. Thus far, the moderately effective nitazoxanide is the only drug approved by the United States Food and Drug Administration for treating cryptosporidiosis in immunocompetent humans. However, no effective drug exists for the severe disease seen in young children, immunocompromised individuals and neonatal livestock. C. parvum lacks the Krebs cycle and the oxidative phosphorylation steps, making it dependent solely on glycolysis for metabolic energy production. Within its glycolytic pathway, C. parvum possesses two unique enzymes, the bacterial-type lactate dehydrogenase (CpLDH) and the plant-like pyruvate kinase (CpPyK), that catalyze two sequential steps for generation of essential metabolic energy. We have previously reported that inhibitors of CpLDH are effective against C. parvum, both in vitro and in vivo. Herein, we developed an in vitro assay for the enzymatic activity of recombinant CpPyK protein and used it to screen a chemical compound library for inhibitors of CpPyK's activity. The identified inhibitors were tested (at non-toxic concentrations) for efficacy against C. parvum using in vitro assays, and an in vivo mouse infection model. We identified six CpPyK inhibitors that blocked in vitro growth and proliferation of C. parvum at low micromolar concentrations (EC50 values ranging from 10.29 to 86.01 µM) that were non-toxic to host cells. Among those six compounds, two (NSC252172 and NSC234945) were found to be highly efficacious against cryptosporidiosis in immunocompromised mice at a dose of 10 mg/kg body weight, with very significant reduction in parasite load and amelioration of intestinal pathologies. Together, these findings have unveiled inhibitors for an essential molecular target in C. parvum and demonstrated their efficacy against the parasite in vitro and in vivo. These inhibitors are, therefore, potential lead-compounds for developing efficacious treatments for cryptosporidiosis.

14.
ACS Omega ; 5(28): 17703-17714, 2020 Jul 21.
Article in English | MEDLINE | ID: mdl-32715257

ABSTRACT

Cu2O nanospheres (NSs) were synthesized by modifying the glucose reduction method. Based on this method, Cu2O/Au (Ag) NSs were further prepared by in situ reduction of HAuCl4 (via electron beam evaporation of Ag). With Rhodamine 6G (R6G) as probe, the surface-enhanced Raman scattering (SERS) characteristics of the three samples were systematically studied. The experiment results showed that the enhancement factor (EF) of Cu2O/Au (Ag) NSs as 1.25 × 108 (2.74 × 109) and the ultralow detection limit (LOD) as 8.07 × 10-12 (1.13 × 10-13) M for R6G. The excellent performance of SERS may be due to the charge transfer (CT) between metal-semiconductor (MS) molecules and the strong electromagnetic field (E-field) of each hot spot. In addition, discrete dipole approximation (DDA) simulations were performed to simulate the E-field enhancement of the Cu2O and Cu2O/Au (Ag) NSs in a three-dimensional (3D) configuration. These further supported that the high SERS performance for R6G is because of the powerful E-field coupling between neighboring Au (Ag) NPs and the surface plasmon resonance (SPR) effect. The Cu2O/Ag NSs have potential in applications such as biomedicine, food safety, and environmental monitoring because of their high sensitivity and good reproducibility.

15.
Nanomaterials (Basel) ; 10(6)2020 May 30.
Article in English | MEDLINE | ID: mdl-32486223

ABSTRACT

Active photonics based on graphene has attracted wide attention for developing tunable and compact optical devices with excellent performances. In this paper, the dynamic manipulation of electromagnetically induced transparency (EIT) with high quality factors (Q-factors) is realized in the optical telecommunication range via the graphene-loaded all-dielectric metasurface. The all-dielectric metasurface is composed of split Si nanocuboids, and high Q-factor EIT resonance stems from the destructive interference between the toroidal dipole resonance and the magnetic dipole resonance. As graphene is integrated on the all-dielectric metasurface, the modulation of the EIT window is realized by tuning the Fermi level of graphene, engendering an appreciable modulation depth of 88%. Moreover, the group velocity can be tuned from c/1120 to c/3390. Our proposed metasurface has the potential for optical filters, modulators, and switches.

16.
Opt Lett ; 45(4): 823-826, 2020 Feb 15.
Article in English | MEDLINE | ID: mdl-32058479

ABSTRACT

Recent advances in nanotechnology have prompted the need for tools to accurately and noninvasively manipulate individual nano-objects. Among the possible strategies, optical forces have been widely used to enable nano-optical tweezers capable of trapping or moving a specimen with unprecedented accuracy. Here, we propose an architecture consisting of a nanotip excited with a plasmonic vortex enabling effective dynamic control of nanoparticles in three dimensions. The structure illuminated by a beam with angular momentum can generate an optical field that can be used to manipulate single dielectric nanoparticles. We demonstrate that it is possible to stably trap or push the particle from specific points, thus enabling a new, to the best of our knowledge, platform for nanoparticle manipulation.

17.
Exp Eye Res ; 190: 107892, 2020 01.
Article in English | MEDLINE | ID: mdl-31811822

ABSTRACT

Neuronal excitotoxicity caused by over activation of N -Methyl-D-Aspartate (NMDA) receptors is an important risk factor for the retinal ganglion cells (RGCs) death in glaucoma. D-serine played a role as a key co-agonist for NMDA receptor activity and neurotoxicity. Our previous studies have demonstrated that increased D-serine and serine racemase (SR) expression in the retina of the chronic intraocular hypertension (COH) model were detected. D-amino acid oxidase (DAAO) treatment significantly increased RGCs survival in the glaucomatous eyes. However, the molecular mechanism remains unclear. In the present study, we investigated the extracellular signal-regulated protein kinase1/2 (ERK1/2) signaling pathway involved in DAAO neuroprotective effects on RGC survival and explore the effect of inhibited ERK1/2 phosphorylation on RGC survival and Müller cell activation in a COH rat model. We found that ERK1/2 phosphorylation and p38 kinase (p38) phosphorylation increased in the COH model, while c-Jun N-terminal kinase (JNK) phosphorylation didn't change. DAAO treatment induced ERK-1/2 MAP kinase phosphorylation and its upstream regulator, p-MEK increased in the COH model. The increased p-ERK was mainly located in retinal Müller cells. In contrast, p-JNK and p-p38 protein expression was not significantly different under these conditions. Quantitative analysis of RGC survival by fluorescent labeling and TdT-mediated dUTP nick-end labeling (TUNEL) assays confirmed that p-ERK1/2 inhibition by PD98059 attenuates DAAO-mediated reductions in RGC apoptosis. Additionally, p-ERK1/2 inhibition induced elevated glial fibrillary acidic protein (GFAP) expression in Müller cells in the COH model. Together, these results suggest that the ERK1/2 signaling pathway is involved in DAAO's neuroprotective effects on RGC survival.


Subject(s)
D-Amino-Acid Oxidase/pharmacology , Disease Models, Animal , Glaucoma/drug therapy , MAP Kinase Signaling System/drug effects , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Neuroprotective Agents/pharmacology , Animals , Blotting, Western , Ependymoglial Cells/metabolism , Flavonoids/pharmacology , Fluorescent Antibody Technique, Indirect , Glaucoma/enzymology , Glial Fibrillary Acidic Protein/metabolism , In Situ Nick-End Labeling , Male , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Phosphorylation , Protein Kinase Inhibitors/pharmacology , Rats , Rats, Wistar , Retinal Ganglion Cells/drug effects , Retinal Ganglion Cells/enzymology
18.
Sci Rep ; 9(1): 19457, 2019 Dec 19.
Article in English | MEDLINE | ID: mdl-31857607

ABSTRACT

Layered transitional metal dichalcogenides (TMDs) are drawing significant attentions for the applications of optics and optoelectronics. To achieve optimal performances of functional devices, precisely controlled doping engineering of 2D TMDs alloys has provided a reasonable approach to tailor their physical and chemical properties. By the chemical vapor transport (CVT) method and liquid phase exfoliation technique, in this work, we synthesized WS1.76Te0.24 saturable absorber (SA) which exhibited high-performance of nonlinear optics. The nonlinear saturable absorption of the WS1.76Te0.24 SA was also measured by the open aperture Z-scan technique. Compared to that of the binary component WS2 and WTe2, WS1.76Te0.24 SA has shown 4 times deeper modulation depth, 28% lower saturable intensity and a much faster recovery time of 3.8 ps. The passively Q-switched laser based on WS1.76Te0.24 was more efficient, with pulse duration narrowed to 18%, threshold decreased to 28% and output power enlarged by 200%. The promising findings can provide a method to optimize performances of functional devices by doping engineering.

19.
PLoS Pathog ; 15(7): e1007953, 2019 07.
Article in English | MEDLINE | ID: mdl-31356619

ABSTRACT

Cryptosporidium parvum is a highly prevalent zoonotic and anthroponotic protozoan parasite that causes a diarrheal syndrome in children and neonatal livestock, culminating in growth retardation and mortalities. Despite the high prevalence of C. parvum, there are no fully effective and safe drugs for treating infections, and there is no vaccine. We have previously reported that the bacterial-like C. parvum lactate dehydrogenase (CpLDH) enzyme is essential for survival, virulence and growth of C. parvum in vitro and in vivo. In the present study, we screened compound libraries and identified inhibitors against the enzymatic activity of recombinant CpLDH protein in vitro. We tested the inhibitors for anti-Cryptosporidium effect using in vitro infection assays of HCT-8 cells monolayers and identified compounds NSC158011 and NSC10447 that inhibited the proliferation of intracellular C. parvum in vitro, with IC50 values of 14.88 and 72.65 µM, respectively. At doses tolerable in mice, we found that both NSC158011 and NSC10447 consistently significantly reduced the shedding of C. parvum oocysts in infected immunocompromised mice's feces, and prevented intestinal villous atrophy as well as mucosal erosion due to C. parvum. Together, our findings have unveiled promising anti-Cryptosporidium drug candidates that can be explored further for the development of the much needed novel therapeutic agents against C. parvum infections.


Subject(s)
Antiprotozoal Agents/pharmacology , Cryptosporidium parvum/drug effects , Cryptosporidium parvum/enzymology , Enzyme Inhibitors/pharmacology , L-Lactate Dehydrogenase/antagonists & inhibitors , Protozoan Proteins/antagonists & inhibitors , Animals , Cell Line , Cryptosporidiosis/drug therapy , Cryptosporidiosis/parasitology , Cryptosporidiosis/pathology , Cryptosporidium parvum/pathogenicity , Host-Parasite Interactions/drug effects , Humans , L-Lactate Dehydrogenase/chemistry , L-Lactate Dehydrogenase/genetics , Mice , Mice, Knockout , Molecular Docking Simulation , Parasitic Sensitivity Tests , Protozoan Proteins/chemistry , Protozoan Proteins/genetics , Recombinant Proteins/chemistry , Recombinant Proteins/genetics
20.
Light Sci Appl ; 8: 8, 2019.
Article in English | MEDLINE | ID: mdl-30651983

ABSTRACT

In recent years, the two-dimensional (2D) transition metal dichalcogenides (TMDCs) have attracted renewed interest owing to their remarkable physical and chemical properties. Similar to that of graphene, the atomic thickness of TMDCs significantly limits their optoelectronic applications. In this study, we report a hybrid WS2-optical-fiber-nanowire (WOFN) structure for broadband enhancement of the light-matter interactions, i.e., light absorption, photoluminescence (PL) and second-harmonic generation (SHG), through evanescent field coupling. The interactions between the anisotropic light field of an optical fiber nanowire (OFN) and the anisotropic second-order susceptibility tensor of WS2 are systematically studied theoretically and experimentally. In particular, an efficient SHG in the WOFN appears to be 20 times larger than that in the same OFN before the WS2 integration under the same conditions. Moreover, we show that strain can efficiently manipulate the PL and SHG in the WOFN owing to the large configurability of the silica OFN. Our results demonstrate the potential applications of waveguide-coupled TMDCs structures for tunable high-performance photonic devices.

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