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1.
Sci Total Environ ; 803: 150007, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34492492

RESUMO

Satellite-based measures of NO2 have become increasingly available for resolving the limitation on insufficient spatial and temporal coverage of ground-level monitoring networks. Oversampled NO2 column density can obtain more detailed features of NO2 column with a spatial resolution as high as 2 km × 2 km, while it is still challenging to identify hotspots of NOx pollution plume in city-scale due to background interference. In this study, we proposed a method for detecting the NOx hotspot grids from oversampled satellite NO2 column based on the image segmentation method, and identifying major source types using Term frequency-inverse document frequency (TF-IDF). A fractal model was used to evaluate and eliminate the background portion of the NO2 column and an adaptive threshold method was adopted to identify the region of interest (ROI) of local hotspot NO2 column. Hot-grid index, counting the frequency of NO2 hotspot ROI in each grid, was conducted to identify the hotspot grids. TF-IDF was used to semantically analyze the major source types of NO2 hotspot grids. Taking Central and Eastern China as the studied domain, the hotspot grids of NO2 and the relevant major source types were identified based on the proposed method. The major non-road mobile sources (such as Beijing Capital International Airport), industrial areas (such as Caofeidian Industrial Park) and urban areas were clearly distinguished. The power plant, Coke and Iron and Steel were identified as major source types in the whole year in the corresponding NOx hotspot grids. Notably, the identification of hotspot grids indicated a higher probability of a local high-intensity NOx pollution plume rather than a quantitative NOx emission; the key source types were the semantic keywords in hotspot grids, which does not mean there were no other exiting emission sources. This proposed method has strong implications on rapidly identifying the NOx hotspot grids based on oversampled TROPOMI NO2 column and the list of industrial enterprises.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Cidades , Monitoramento Ambiental , Dióxido de Nitrogênio/análise
2.
Neural Regen Res ; 17(1): 194-202, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34100456

RESUMO

Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 µL exosomes via the tail vein (200 µg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1ß release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.

3.
Mol Ther Nucleic Acids ; 26: 798-812, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34729249

RESUMO

Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease. The lack of targeted therapies and poor patient outcome have fostered efforts to discover new molecular targets to treat patients with TNBC. Here, we showed that baculoviral IAP repeat containing 6 (BIRC6) is overexpressed and positively correlated with epidermal growth factor (EGF) receptor (EGFR) in TNBC cells and tissues and that BIRC6 overexpression is associated with poor patient survival. Mechanistic studies revealed that BIRC6 stability is increased by EGF-JNK signaling, which prevents ubiquitination and degradation of BIRC6 mediated by the E3 ubiquitin ligase HECTD1. BIRC6 in turn decreases SMAC expression by inducing the ubiquitin-proteasome pathway, thereby antagonizing apoptosis and promoting the proliferation, colony formation, tumorsphere formation, and tumor growth capacity of TNBC cells. Therapeutically, the PEGylated cationic lipid nanoparticle (pCLN)-assisted delivery of BIRC6 small interfering RNA (siRNA) efficiently silences BIRC6 expression in TNBC cells, thus suppressing TNBC cell growth in vitro and in vivo, and its antitumor activity is significantly superior to that of the EGFR inhibitor gefitinib. Our findings identify an important regulatory mechanism of BIRC6 overexpression and provide a potential therapeutic option for treating TNBC.

4.
J Med Chem ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34779204

RESUMO

VPS34 is a class III phosphoinositide 3-kinase involved in endosomal trafficking and autophagosome formation. Inhibitors of VPS34 were believed to have value as anticancer agents, but genetic and pharmacological data suggest that sustained inhibition of VPS34 kinase activity may not be well tolerated. Here we disclose the identification of a novel series of dihydropyrazolopyrazinone compounds represented by compound 5 as potent, selective, and orally bioavailable VPS34 inhibitors through a structure-based design strategy. A water-interacting hydrogen bond acceptor within an appropriate distance to a hinge-binding element was found to afford significant VPS34 potency across chemical scaffolds. The selectivity of compound 5 over PIK family kinases arises from interactions between the hinge-binding element and the pseudo-gatekeeper residue Met682. As recent in vivo pharmacology data suggests that sustained inhibition of VPS34 kinase activity may not be tolerated, structure-activity relationships leading to VPS34 inhibition may be helpful for avoiding this target in other ATP-competitive kinase programs.

5.
Eur Radiol ; 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34800150

RESUMO

OBJECTIVES: We tried to realize accurate pathological classification, assessment of prognosis, and genomic molecular typing of renal cell carcinoma by CT texture feature analysis. To determine whether CT texture features can perform accurate pathological classification and evaluation of prognosis and genomic characteristics in renal cell carcinoma. METHODS: Patients with renal cell carcinoma from five open-source cohorts were analyzed retrospectively in this study. These data were randomly split to train and test machine learning algorithms to segment the lesion, predict the histological subtype, tumor stage, and pathological grade. Dice coefficient and performance metrics such as accuracy and AUC were calculated to evaluate the segmentation and classification model. Quantitative decomposition of the predictive model was conducted to explore the contribution of each feature. Besides, survival analysis and the statistical correlation between CT texture features, pathological, and genomic signatures were investigated. RESULTS: A total of 569 enhanced CT images of 443 patients (mean age 59.4, 278 males) were included in the analysis. In the segmentation task, the mean dice coefficient was 0.96 for the kidney and 0.88 for the cancer region. For classification of histologic subtype, tumor stage, and pathological grade, the model was on a par with radiologists and the AUC was 0.83 [Formula: see text] 0.1, 0.80 [Formula: see text] 0.1, and 0.77 [Formula: see text] 0.1 at 95% confidence intervals, respectively. Moreover, specific quantitative CT features related to clinical prognosis were identified. A strong statistical correlation (R2 = 0.83) between the feature crosses and genomic characteristics was shown. The structural equation modeling confirmed significant associations between CT features, pathological (ß = - 0.75), and molecular subtype (ß = - 0.30). CONCLUSIONS: The framework illustrates high performance in the pathological classification of renal cell carcinoma. Prognosis and genomic characteristics can be inferred by quantitative image analysis. KEY POINTS: • The analytical framework exhibits high-performance pathological classification of renal cell carcinoma and is on a par with human radiologists. • Quantitative decomposition of the predictive model shows that specific texture features contribute to histologic subtype and tumor stage classification. • Structural equation modeling shows the associations of genomic characteristics to CT texture features. Overall survival and molecular characteristics can be inferred by quantitative CT texture analysis in renal cell carcinoma.

6.
Mater Horiz ; 8(6): 1690-1699, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34846499

RESUMO

Developing materials with tailorable properties has been the long-sought goal of humankind. Forming composite materials with superior properties by combining two or more materials has emerged as a competitive means in the search and design of new materials. However, it is still a grand challenge to use metallic materials as a binder for composites because of their lack of adhesion. In the present work, we proposed a facile and flexible route to synthesize composites using metallic glass as a glue to bond various materials, ranging from conductors to insulators, and metals to nonmetals, together. The mechanical, magnetic and electrical performances of the composites can be manually regulated by changing the addition ratios of the metallic glass glue and the corresponding admixture. In addition, porous structures were also obtained and tuned by dissolving the soluble admixture in water. In principle, our approach provides a new idea for the fabrication and optimization of composites using metallic materials as binders. The outcome of our current research opens up a window not only to synthesize composite materials with tailorable properties universally and flexibly, but also towards the discovery of potential multi-functional metal containing composites.

7.
Vaccine ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34815117

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic. Safe and effective COVID-19 vaccines are now available, including mRNA-1273, which has shown 94% efficacy in prevention of symptomatic COVID-19 disease. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several variants have shown decreased susceptibility to neutralization by vaccine-induced immunity, most notably B.1.351 (Beta), although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of 2 updated mRNA vaccines designed to target SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the spike protein found in B.1.351 and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against B.1.351, while mRNA-1273.211 was effective at providing broad cross-variant neutralization. A third (booster) dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are being evaluated in pre-clinical challenge and clinical studies.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34816709

RESUMO

Antimicrobial resistance in Gram-negative bacteria has become one of the leading causes of morbidity and mortality and a serious worldwide public health concern due to the fact that Gram-negative bacteria have an additional outer membrane protecting them from an unwanted compound invading. It is still very difficult for antimicrobials to reach intracellular targets and very challenging to treat Gram-negative bacteria with the current strategies. Here, we found that (o-(bromomethyl)phenyl)boronic acid was incorporated into poly((2-N,N-diethyl)aminoethyl acrylate) (PDEA), forming a copolymer (poly(o-Bn-DEA)) having both phenylboronic acid (B) and ((2-N,N-diethyl)amino) (DEA) units. Poly(o-Bn-DEA) exhibits very strong intramolecular B-N coordination, which could highly promote the covalent binding of phenylboronic acid with lipopolysaccharide (LPS) on the outer membrane of E. coli and lodge poly(o-Bn-DEA) on the LPS layer on the surface of E. coli. Meanwhile, the strong electrostatic interaction between poly(o-Bn-DEA) and the negatively charged lipid preferred tugging the poly(o-Bn-DEA) into the lipid bilayer of E. coli. The combating interactions between covalent binding and electrostatic interaction form a tug-of-war action, which could trigger the lysis of the outer membrane, thereby killing Gram-negative E. coli effectively without detectable resistance.

9.
Mater Horiz ; 8(1): 267-275, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34821305

RESUMO

The development of intrinsic self-healing elastomers with simultaneous high mechanical strength, toughness and room-temperature reparability remains a formidable challenge. Herein, we report a mechano-responsive strategy, known as strain induced crystallization, to address the above issue, whereby synthesized elastomers with unprecedented high mechanical performances are bestowed with room-temperature self-healing materials, achieving tensile strength, toughness and fracture energy values of 29.0 MPa, 121.8 MJ m-3 and 104.1 kJ m-2, respectively.

10.
Gut ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34836916

RESUMO

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34779551

RESUMO

Supramolecular catalysis of artificial synthetic-hosts is originally bio-inspired for reactivities intrinsic to enzymes, but more exceptional properties and functions may be expected beyond enzyme mimics. Herein we demonstrate that, based on the creation of dynamic nanospaces in solution by highly charged positive coordination cage of [Pd 6 (RuL 3 ) 8 ] 28+ , multirole and multi-way cageconfined catalysis is accomplishable for versatile functions and anomalous reactivities with the aid of biomimetic cage effect. The high cationic-host charges drive partial deprotonation of 24 imidazole-NHs on cage sphere alike imidazole-residuals in proteins, generating amphoteric heterogeneity in solution to enforce effective cavitybasicity against solution-acidity. Synergistic actions arisen from cage hydrophobicity, host-guest electrostatic interactions and imidazole-N coordination facilitate C(sp)-H activation and carbanionic intermediate stabilization of terminal alkynes to achieve unusual H/D-exchange and Glaser coupling under acidic conditions, and enable phase transfers of water-insoluble substrates/products/co-catalysts to make immiscible-phase and bi-phase catalysis feasible, thus providing a useful catalytic protocol to combine merits from homogeneous, heterogeneous, enzymatic and phase transfer catalysis.

12.
Micromachines (Basel) ; 12(11)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34832725

RESUMO

MEMS resonators have become core devices in a large number of fields; however, due to their complex structures, the finite element analysis (FEA) method is still the main method for their theoretical analysis. The traditional finite element analysis method faces the disadvantages of large calculation amount and long simulation time, which limits the development of high-performance MEMS resonators. This paper demonstrates a high-speed and high-accuracy simulation tool based on the artificial neural network, where a multilayer perceptron (MLP) neural network model is constructed. The typical structural parameters of MEMS resonator are used as the input layer, and its performance indicators produced by the finite element analysis method are the output layer. After iteratively trained with 4000 samples, the cumulative error of the neural network decreases to 0.0017 and a prediction network model is obtained. Compared with the finite element analysis results, the structural accuracy error predicted by the neural network model can be controlled within 6%, but its runtime is shortened by 15,000 times. This high-speed and high-accuracy mathematical modeling method can effectively improve the analyzing efficiency and provide a promising tool for the design and optimization of different complex MEMS resonators, which exhibit remarkable accuracy and speed.

13.
Environ Pollut ; : 118595, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34843848

RESUMO

Although an association between urinary phthalate (PAE) metabolites and respiratory symptoms and diseases has been reported, knowledge regarding its effect on pulmonary function is limited, especially in adolescents. Using cross-sectional data from 1389 adolescents (aged 10-19 years) in the 2007-2012 National Health and Nutrition Examination Survey, the association of mixed urinary PAE metabolites with pulmonary function was evaluated using the weighted quantile sum. Moreover, multivariate linear regression was performed to investigate associations between each urinary PAE metabolite and pulmonary function indicators and to estimate the interaction effects between urinary PAE metabolites and demographic characteristics. We found that mixed urinary PAE metabolites were negatively associated with forced expiratory volume at the 1 s (FEV1, p < 0.001) and forced vital capacity (FVC, p = 0.008) levels. In individual PAE metabolite analyses, mono (carboxynonyl) pthalate (MCNP), mono-n-butyl pthalate (MnBP), mono-isobutyl pthalate (MiBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-benzyl phthalate (MBzP) correlated negatively with both FVC and FEV1 values (Holm-Bonferroni corrected p < 0.05). Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was negatively associated with the FVC value. Significant interactions between sex and urinary MnBP or MBzP levels for the risk of FEV1 decrease in girls were found (p = 0.005), as was a significant interaction between sex and urinary MBzP level for the risk of FVC decline. Our findings suggest that higher PAE exposure is associated with respiratory dysfunction; the association is more pronounced among girls.

14.
Cancer Cell Int ; 21(1): 637, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34844621

RESUMO

BACKGROUND: Esophageal carcinogenesis is a multifactorial process in which genetic and environmental factors interact to activate intracellular signals, leading to the uncontrolled survival and growth of esophageal squamous cell carcinoma (ESCC) cells. The intracellular pathways of ESCC cells could be regulated by proteinase activated-receptors (PARs), which are comprised of four receptors (i.e., PAR-1, PAR-2, PAR-3, and PAR-4). Therefore, the function and possible mechanism of PAR1 and PAR4 in the progression of ECSS were explored in our study. METHODS: First, we detected the expression levels of PAR1 and PAR4 in 27 cases of ESCC specimens and cell lines by RT-qPCR, IHC and western blot. Meanwhile, the correlation between PAR1/PAR4 expression levels, clinicopathological characteristics, and disease free survival was analyzed. Then, we constructed PAR1/PAR4 knockdown cell models and investigated the role of PAR1/PAR4 knockdown on the proliferation, apoptosis, changes of calcium flow, and metastasis of ESCC cells via MTT, flow cytometry, transwell and wound healing assays in vitro. Further, an experimental metastasis model in vivo was established to explore the role of stable PAR1/PAR4 knockdown on the growth and metastasis of ESCC cells. Finally, the role of nSMase2 in the activation of NF-κB induced by PAR4 and the role of NF-κB and STAT3 signaling pathways in the PAR1/PAR4-mediated tumor promoting or suppressive functions were measured by immunoprecipitation, western blot and immunofluorescence assays. RESULTS: First, the integrated results demonstrated the expression levels of PAR1 and PAR4 are inversely proportional in ESCC. PAR1 potently enhanced tumor growth and metastasis, while PAR4 had an inhibitory effect. Further, the co-activation of STAT3 and NF-κB was involved in the PAR1 activation-induced tumor promoting effect, while only NF-κB participated in the PAR4 activation-induced tumor inhibitory effect in ESCC. To be specific, FAK/PI3K/AKT/STAT3/NF-κB signaling mediated PAR1 activation-induced tumor promoting effect and nSMase2/MAPK/NF-κB signaling mediated PAR4 activation-induced tumor inhibitory effect. CONCLUSIONS: Overall, the study has provided new insights into the potential implication of PAR1 and PAR4 in the pathogenesis of ESCC. Besides, FAK/PI3K/AKT/STAT3/NF-κB and nSMase2/MAPK/NF-κB pathways may be novel targets for regulating tumor growth and metastasis in ESCC patients.

15.
Sci Rep ; 11(1): 19716, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611243

RESUMO

It was still unclear how homocysteine (Hcy) levels and cognitive deficits change in patients with schizophrenia of various ages. The present article attempts to assess the relationship between Hcy levels and cognitive deficits in patients with schizophrenia across age groups, especially in young people. Totals of 103 patients and 122 healthy controls were included. All participants were stratified into four groups according to their age: 18-29 years, 30-39 years, 40-49 years, and 50-59 years. Clinical data, plasma Hcy levels, and cognitive function score were collected. Cognitive function was evaluated using the MATRICS Consensus Cognitive Battery of tests assessing speed of processing, verbal learning and memory, visual learning and memory, working memory, and attention/vigilance. Compared with the healthy group, Hcy levels increased significantly, and all the measured cognitive function score were significantly lower in all age groups of patients with schizophrenia (p < 0.001). Hcy levels were negatively associated with speed of processing (SoP), working memory (WM), and visual learning and memory (Vis Lrng) score in 18-29 years. Further multiple regression analysis showed that SoP were independently associated with Hcy levels in patients with schizophrenia aged 18-29 years (B = 0.74, t = 3.12, p = 0.008). Based on our results, patients with schizophrenia performed worse on cognitive assessments and Hcy levels were more closely related to cognition in young patients.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34699166

RESUMO

Following spinal cord injury (SCI), the transmission of electrical signals is interrupted, and an oxidative microenvironment is generated, hindering nerve regeneration and functional recovery. The strategies of regulating oxidative pathological microenvironment while restoring endogenous electrical signal transmission hold promise for SCI treatment. However, challenges are still faced in simply fabricating bioactive scaffolds with both antioxidation and conductivity. Herein, aiming to construct an antioxidative and conductive microenvironment for nerve regeneration, the difunctional polypyrrole (PPy) nanoparticles were developed and incorporated into bioactive collagen/hyaluronan hydrogel. Owing to the embedded PPy in hydrogel, the encapsulated bone marrow mesenchymal stem cells (BMSCs) can be protected from oxidative damage, and their neuronal differentiation was promoted by the synergy between conductivity and electrical stimulation, which is proved to be related to PI3K/Akt and the mitogen-activated protein kinase (MAPK) pathway. In SCI rats, the BMSC-laden difunctional hydrogel restored the transmission of bioelectric signals and inhibited secondary damage, thereby facilitating neurogenesis, resulting in prominent nerve regeneration and functional recovery. Overall, taking advantage of a difunctional nanomaterial to meet two essential requirements in SCI repair, this work provides intriguing insights into the design of biomaterials for nerve regeneration and tissue engineering.

20.
Int J Ophthalmol ; 14(10): 1463-1472, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34667721

RESUMO

AIM: To investigate the effect of Staphylococcus aureus (S. aures) lysates (SALs) on herpes simplex virus type-I (HSV1) infection in human corneal epithelial (HCE) cells and in a mouse model of HSV1 keratitis. METHODS: HCE, Vero, HeLa, and BV2 cells were infected with HSV1 [HSV1 f strain, HSV1f; HSV-1-H129 with green fluorescent protein (GFP) knock-in, HSV1g]. Pre- or post-infection, SAL at various concentrations was added to the culture medium for 24h. GFP fluorescence in HSV1g or plaque formation by HSV1f were examined. The effects of heat-treated SAL, precooled acetone-precipitated SAL, and SAL subjected to ultrafiltration (100 kDa) were evaluated. The effects of other bacterial components and lysates on HSV1 infection were also tested, including lipoteichoic acid (LTA), peptidoglycan (PGN), staphylococcal protein A (SPA), and α-hemolysin from S. aureus (α-toxin) as well as lysates from a wild-type S. aureus strain, S. epidermidis, and Escherichia coli (W-SAL, SEL, and ECL, respectively). In addition, SAL eye drops were applied topically to BALB/c mice with HSV1 keratitis, followed by in vivo observations. RESULTS: The cytopathic effect, plaque formation (HSV1f), and GFP expression (HSV1g) in infected cells were inhibited by SAL in a dose-dependent manner. The active component of SAL (≥100 kDa) was heat-sensitive and retained activity after acetone precipitation. In HSV1g-infected cells, treatment with LTA-sa, α-toxin, PGN-sa, or SPA did not inhibit GFP expression. SAL, W-SAL, and SEL (but not ECL) decreased GFP expression. In mice with HSV1 keratitis, SAL reduced corneal lesions by 71%. CONCLUSION: The results of this study demonstrate that SAL can be used to inhibit HSV1 infection, particularly keratitis. Further studies are needed to determine the active components and mechanism underlying the effects of SAL.

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