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Zoonotic coronaviruses pose a continuous threat to human health, with newly identified bat-borne viruses like swine acute diarrhea syndrome coronavirus (SADS-CoV) causing high mortality in piglets. In vitro studies indicate that SADS-CoV can infect cell lines from diverse species, including humans, highlighting its potential risk to human health. However, the lack of tools to study viral entry, along with the absence of vaccines or antiviral therapies, perpetuates this threat. To address this, we engineered an infectious molecular clone of Vesicular Stomatitis Virus (VSV), replacing its native glycoprotein (G) with SADS-CoV spike (S) and inserting a Venus reporter at the 3' leader region to generate a replication-competent rVSV-Venus-SADS S virus. Serial passages of rVSV-Venus-SADS S led to the identification of an 11-amino-acid truncation in the cytoplasmic tail of the S protein, which allowed more efficient viral propagation due to increased cell membrane anchoring of the S protein. The S protein was integrated into rVSV-Venus-SADS SΔ11 particles, susceptible to neutralization by sera from SADS-CoV S1 protein-immunized rabbits. Additionally, we found that TMPRSS2 promotes SADS-CoV spike-mediated cell entry. Furthermore, we assessed the serum-neutralizing ability of mice vaccinated with rVSV-Venus-SADS SΔ11 using a prime-boost immunization strategy, revealing effective neutralizing antibodies against SADS-CoV infection. In conclusion, we have developed a safe and practical tool for studying SADS-CoV entry and exploring the potential of a recombinant VSV-vectored SADS-CoV vaccine.IMPORTANCEZoonotic coronaviruses, like swine acute diarrhea syndrome coronavirus (SADS-CoV), pose a continual threat to human and animal health. To combat this, we engineered a safe and efficient tool by modifying the Vesicular Stomatitis Virus (VSV), creating a replication-competent rVSV-Venus-SADS S virus. Through serial passages, we optimized the virus for enhanced membrane anchoring, a key factor in viral propagation. This modified virus, rVSV-Venus-SADS SΔ11, proved susceptible to neutralization, opening avenues for potential vaccines. Additionally, our study revealed the role of TMPRSS2 in SADS-CoV entry. Mice vaccinated with rVSV-Venus-SADS SΔ11 developed potent neutralizing antibodies against SADS-CoV. In conclusion, our work presents a secure and practical tool for studying SADS-CoV entry and explores the promise of a recombinant VSV-vectored SADS-CoV vaccine.
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Alphacoronavirus , Internalização do Vírus , Replicação Viral , Animais , Humanos , Camundongos , Coelhos , Alphacoronavirus/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linhagem Celular , Chlorocebus aethiops , Infecções por Coronavirus/virologia , Infecções por Coronavirus/prevenção & controle , Células HEK293 , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Serina Endopeptidases/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Suínos , Células Vero , Vírus da Estomatite Vesicular Indiana/genética , Vesiculovirus/genética , Vacinas Virais/imunologia , Vacinas Virais/genéticaRESUMO
Swine acute diarrhea syndrome coronavirus (SADS-CoV) has caused severe intestinal diseases in pigs. It originates from bat coronaviruses HKU2 and has a potential risk of cross-species transmission, raising concerns about its zoonotic potential. Viral entry-related host factors are critical determinants of susceptibility to cells, tissues, or species, and remain to be elucidated for SADS-CoV. Type II transmembrane serine proteases (TTSPs) family is involved in many coronavirus infections and has trypsin-like catalytic activity. Here we examine all 18 members of the TTSPs family through CRISPR-based activation of endogenous protein expression in cells, and find that, in addition to TMPRSS2 and TMPRSS4, TMPRSS13 significantly facilitates SADS-CoV infection. This is confirmed by ectopic expression of TMPRSS13, and specific to trypsin-dependent SADS-CoV. Infection with pseudovirus bearing SADS-CoV spike protein indicates that TMPRSS13 acts at the entry step and is sensitive to serine protease inhibitor Camostat. Moreover, both human and pig TMPRSS13 are able to enhance the cell-cell membrane fusion and cleavage of spike protein. Overall, we demonstrate that TMPRSS13 is another host serine protease promoting the membrane-fusion entry of SADS-CoV, which may expand its host tropism by using diverse TTSPs.
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Proteínas de Membrana , Serina Endopeptidases , Internalização do Vírus , Animais , Serina Endopeptidases/metabolismo , Serina Endopeptidases/genética , Suínos , Humanos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Alphacoronavirus/genética , Alphacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Infecções por Coronavirus/metabolismo , Gabexato/análogos & derivados , Gabexato/farmacologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Células HEK293 , Linhagem Celular , Chlorocebus aethiops , Doenças dos Suínos/virologia , Ésteres , GuanidinasRESUMO
MXenes with excellent conductivity and abundant surface functional groups have displayed great advantages as platforms for sensing materials. NiO also has drawn much attention for gas detection due to its unique merits of excellent catalytic activity. Herein, NiO nanoparticles are incorporated with multilayer Ti3C2Tx-MXene to develop excellent triethylamine sensors. Due to the larger specific surface area and formed p-p heterojunctions, the response of the NiO/Ti3C2Tx gas sensor is endowed with a response value of 950% to 50 ppm triethylamine gas and is much higher than that of the pristine NiO sensor. Moreover, the NiO/Ti3C2Tx sensor displays a fast response time of 8 s (50 ppm triethylamine), excellent reproducibility, and reliable long-term stability. This study proves that NiO/Ti3C2Tx sensors have potential for the effective detection of triethylamine gas.
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The bimetallic metal-organic frameworks (MOFs), Cu/Co-MOF, was synthesized through a solvothermal method and calcined to obtain CuO/Co3O4composites. By adjusting the molar ratio between Cu and Co ions, a composite material of CuO/Co3O4(Cu:Co = 1:1) was developed and showed excellent sensing capabilities, and the response reached as high as 196.3 for 10 ppm H2S detection. Furthermore, the optimal operating temperature as low as 40 °C was found. In comparison with the sensors prepared by pristine CuO and pristine Co3O4, the sensor based on CuO/Co3O4composite exhibited a significant response. Additionally, the sensor can detect H2S gas down to 300 ppb. The gas sensing mechanism is discussed in depth from the perspective of p-p heterojunction formation between the p-type CuO and p-type Co3O4. The as-prepared CuO/Co3O4composite-based sensor is expected to find practical application in the low-power monitoring of H2S.
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BACKGROUND: Chinese topography appears a three-rung ladder-like distribution of decreasing elevation from northwest to southeast, which is divided by two sloping edges. Previous studies have reported that prevalence of thyroid diseases differed by altitude, and geographical factors were associated with thyroid disorders. To explore the association between three-rung ladder-like regions and thyroid disorders according to unique Chinese topographic features, we conducted an epidemiological cross-sectional study from 2015-2017 that covered all 31 mainland Chinese provinces. METHODS: A total of 78,470 participants aged ≥ 18 years from a nationally representative cross-sectional study were included. Serum thyroid peroxidase antibody, thyroglobulin antibody, and thyroid-stimulating hormone levels; urine iodine concentration; and thyroid volume were measured. The three-rung ladder-like distribution of decreasing elevation from northwest to southeast in China was categorized into three topographic groups according to elevation: first ladder, > 3000 m above sea level; second ladder, descending from 3000-500 m; and third ladder, descending from 500 m to sea level. The third ladder was further divided into groups A (500-100 m) and B (< 100 m). Associations between geographic factors and thyroid disorders were assessed using linear and binary logistic regression analyses. RESULTS: Participants in the first ladder group were associated with lower thyroid peroxidase (ß = -4.69; P = 0.00), thyroglobulin antibody levels (ß = -11.08; P = 0.01), and the largest thyroid volume (ß = 1.74; P = 0.00), compared with the other groups. The second ladder group was associated with autoimmune thyroiditis (odds ratio = 1.30, 95% confidence interval [1.18-1.43]) and subclinical hypothyroidism (odds ratio = 0.61, 95%confidence interval [0.57-0.66]) (P < 0.05) compared with the first ladder group. Group A (third ladder) (500-100 m) was associated with thyroid nodules and subclinical hypothyroidism (P < 0.05). Furthermore, group B (< 100 m) was positively associated with autoimmune thyroiditis, thyroid peroxidase and thyroglobulin antibody positivity, and negatively associated with overt hypothyroidism, subclinical hypothyroidism, and goiter compared with the first ladder group(P < 0.05). CONCLUSION: We are the first to investigate the association between different ladder regions and thyroid disorders according to unique Chinese topographic features. The prevalence of thyroid disorders varied among the three-rung ladder-like topography groups in China, with the exception of overt hyperthyroidism.
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Bócio , Hipotireoidismo , Iodo , Doenças da Glândula Tireoide , Tireoidite Autoimune , Humanos , Tireoglobulina , Estudos Transversais , Altitude , Doenças da Glândula Tireoide/epidemiologia , Hipotireoidismo/epidemiologia , Bócio/epidemiologia , Tireoidite Autoimune/epidemiologia , Iodo/urina , Iodeto Peroxidase , TireotropinaRESUMO
This study integrates hollow microneedle arrays (HMNA) with a novel jellyfish-shaped electrochemical sensor for the detection of key biomarkers, including uric acid (UA), glucose, and pH, in artificial interstitial fluid. The jellyfish-shaped sensor displayed linear responses in detecting UA and glucose via differential pulse voltammetry (DPV) and chronoamperometry, respectively. Notably, the open circuit potential (OCP) of the system showed a linear variation with pH changes, validating its pH-sensing capability. The sensor system demonstrates exceptional electrochemical responsiveness within the physiological concentration ranges of these biomarkers in simulated epidermis sensing applications. The detection linear ranges of UA, glucose, and pH were 0~0.8 mM, 0~7 mM, and 4.0~8.0, respectively. These findings highlight the potential of the HMNA-integrated jellyfish-shaped sensors in real-world epidermal applications for comprehensive disease diagnosis and health monitoring.
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Biomarcadores , Técnicas Biossensoriais , Técnicas Eletroquímicas , Líquido Extracelular , Agulhas , Líquido Extracelular/química , Biomarcadores/análise , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Concentração de Íons de Hidrogênio , Glucose/análise , Ácido Úrico/análise , Animais , HumanosRESUMO
BACKGROUND: Female survivors of childhood cancer are at risk for primary ovarian insufficiency (POI), defined as the cessation of gonadal function before the age of 40 years. We aimed to develop and validate models to predict age-specific POI risk among long-term survivors of childhood cancer. METHODS: To develop models to predict age-specific POI risk for the ages of 21-40 years, we used data from the Childhood Cancer Survivor Study (CCSS). Female survivors aged 18 years or older at their latest follow-up, with self-reported menstrual history information and free of subsequent malignant neoplasms within 5 years of diagnosis, were included. We evaluated models that used algorithms based on statistical or machine learning to consider all predictors, including cancer treatments. Cross-validated prediction performance metrics (eg, area under the receiver operating characteristic curve [AUROC]) were compared to select the best-performing models. For external validation of the models, we used data from 5-year survivors in the St Jude Lifetime Cohort (SJLIFE) with ovarian status clinically ascertained using hormone measurements (menopause defined by follicle stimulating hormone >30 mIU/mL and oestradiol <17 pg/mL) and medical chart or questionnaire review. We also evaluated an SJLIFE-based polygenic risk score for POI among 1985 CCSS survivors with genotype data available. FINDINGS: 7891 female CCSS survivors (922 with POI) were included in the development of the POI risk prediction model, and 1349 female SJLIFE survivors (101 with POI) were included in the validation study. Median follow-up from cancer diagnosis was 23·7 years (IQR 18·3-30·0) in CCSS and 15·1 years (10·4-22·9) in SJLIFE. Between the ages of 21 and 40 years, POI prevalence increased from 7·9% (95% CI 7·3-8·5) to 18·6% (17·3-20·0) in CCSS and 7·3% (5·8-8·9) to 14·9% (11·6-19·1) in SJLIFE. Age-specific logistic regression models considering ovarian radiation dosimetry or prescribed pelvic and abdominal radiation dose, along with individual chemotherapy predictors, performed well in CCSS. In the SJLIFE validation, the prescribed radiation dose model performed well (AUROC 0·88-0·95), as did a simpler model that considered any exposures to pelvic or abdominal radiotherapy or alkylators (0·82-0·90). Addition of the polygenic risk predictor significantly improved the average positive predictive value (from 0·76 [95% CI 0·63-0·89] to 0·87 [0·80-0·94]; p=0·029) among CCSS survivors treated with ovarian radiation and chemotherapy. INTERPRETATION: POI risk prediction models using treatment information showed robust prediction performance in adult survivors of childhood cancer. FUNDING: Canadian Institutes of Health Research, US National Cancer Institute.
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Sobreviventes de Câncer , Neoplasias , Insuficiência Ovariana Primária , Adulto , Humanos , Criança , Feminino , Adulto Jovem , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Insuficiência Ovariana Primária/diagnóstico , Insuficiência Ovariana Primária/epidemiologia , Insuficiência Ovariana Primária/etiologia , Canadá , Sobreviventes , Fatores de Risco , Fatores EtáriosRESUMO
Recent developments in phosphoproteomics have enabled signaling studies where over 10,000 phosphosites can be routinely identified and quantified. Yet, current analyses are limited in sample size, reproducibility, and robustness, hampering experiments that involve low-input samples such as rare cells and fine-needle aspiration biopsies. To address these challenges, we introduced a simple and rapid phosphorylation enrichment method (miniPhos) that uses a minimal amount of the sample to get enough information to decipher biological significance. The miniPhos approach completed the sample pretreatment within 4 h and high effectively collected the phosphopeptides in a single-enrichment format with an optimized enrichment process and miniaturized system. This resulted in an average of 22,000 phosphorylation peptides quantified from 100 µg of proteins and even confidently localized over 4500 phosphosites from as little as 10 µg of peptides. Further application was carried out on different layers of mouse brain micro-sections; our miniPhos method provided quantitative information on protein abundance and phosphosite regulation for the most relevant neurodegenerative diseases, cancers, and signaling pathways in the mouse brain. Surprisingly, the phosphoproteome exhibited more spatial variations than the proteome in the mouse brain. Overall, spatial dynamics of phosphosites are integrated with proteins to gain insights into crosstalk of cellular regulation at different layers, thereby facilitating a more comprehensive understanding of mouse brain development and activity.
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Fosfopeptídeos , Proteoma , Camundongos , Animais , Reprodutibilidade dos Testes , Fosforilação , Proteoma/análise , Fosfopeptídeos/análise , Encéfalo/metabolismoRESUMO
Research efforts have intensified on developing superhydrophobic surfaces on concrete structures to limit the damage caused by the natural porosity and hydrophilicity of cementitious materials. However, the feasibility idea is impeded by the complex preparation process and weak adhesion/stability performance. Therefore, superhydrophobic coatings were rapidly prepared on mortar surfaces by a straightforward and effective one-step method using zinc oxide (ZnO) modified with stearic acid and epoxy resin. The microstructure, physical/chemical properties, hydrophobic properties, and stability of the coatings were systematically investigated. The experimental results showed that the water contact angle of the samples reached a maximum value of 164.2° and a sliding angle of 4.6° when the stearic acid content was 0.5 g. The water absorption of the coated superhydrophobic mortar was reduced by approximately 61% compared to that of ordinary mortar, and neither particulate pollutants nor liquid pollutants could contaminate the superhydrophobic mortar. The coating maintained a superhydrophobic state and exhibited good physical durability after sandpaper abrasion, tape peeling, and high-temperature resistance tests. The water cluster diffusion coefficient on surface of the ordinary coating was 0.1645 × 10-4 and 0.0328 × 10-4 cm2/s on surface of the modified coating after molecular dynamics simulation.
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Glycosylation is one of the most common types of post-translational modifications in mammals. It is well known that N-glycans play a key role in cell adhesion, differentiation, synapsis, and myelination during the development of the mammalian central nervous system (CNS). Neuropathological symptoms (such as epilepsy and Alzheimer's disease) are usually accompanied by N-glycosylation changes. In this study, we extracted N-glycan chains from eight regions of the mouse brain, and combined high-throughput, high-resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) with the Fmoc N-hydroxysuccinimide ester (Fmoc-OSU) derivatization method to improve the sensitivity of glycan detection to characterize the total N-glycans in the mouse brain. A total of 96 N-glycan moieties were detected. An exhaustive examination of the relative abundance of N-glycans, coupled with a comparative analysis of differences, has uncovered discernible variations of statistical significance, including high mannose, fucosylated, sialylated, and galactosylated N-glycans. According to our investigations, a thorough and regionally specific cartography of glycans within the brain can facilitate the investigation of glycan-mediated mechanisms related to both the developmental trajectory and functional output of the brain. Additionally, this approach may serve as a basis for identifying potential biomarkers that are relevant to various brain-associated pathologies.
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Polissacarídeos , Processamento de Proteína Pós-Traducional , Camundongos , Animais , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Polissacarídeos/análise , Glicosilação , Encéfalo/metabolismo , Mamíferos/metabolismoRESUMO
In this study, a series of novel 3-(5-fluoropyridine-3-yl)-2-oxazolidinone derivatives were designed and synthesized based on compounds previously reported, and their antibacterial activity was investigated. Then their antibacterial activity was investigated for the first time. Preliminary screening results showed that all these compounds exhibited antibacterial activity against gram-positive bacteria, including 7 drug-sensitive strains and 4 drug-resistant strains, among which compound 7j exhibited an 8-fold stronger inhibitory effect than linezolid, with a minimum inhibitory concentration (MIC) value of 0.25 µg/mL. Further molecular docking studies predicted the possible binding mode between active compound 7j and the target. Interestingly, these compounds could not only hamper the formation of biofilms, but also have better safety, as confirmed by cytotoxicity experiments. All these results indicate that these 3-(5-fluoropyridine-3-yl)-2-oxazolidinone derivatives have the potential to be developed into novel candidates for the treatment of gram-positive bacterial infections.
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Oxazolidinonas , Oxazolidinonas/farmacologia , Oxazolidinonas/química , Oxindóis/farmacologia , Simulação de Acoplamento Molecular , Piperazina/farmacologia , Antibacterianos/química , Bactérias Gram-Positivas , Pirimidinas/farmacologia , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Estrutura MolecularRESUMO
Triethylamine gas is one of the harmful volatile organic compounds for human health and the ecological environment. Therefore, in order to prevent the detrimental effects of triethylamine gas, it has greatly requirement to be accurately detected. Unfortunately, Cu2O has a low triethylamine gas response and slow recovery. Because of this, we prepared Cu2O/Ti3C2Txnanocomposites by a facile ultrasonication technique. Cu2O is uniformly dispersed on the surface and interlayers of multilayer Ti3C2Txto form a stable hybrid heterostructure. The optimized Cu2O/Ti3C2Txnanocomposite sensor's response to 10 ppm triethylamine at room temperature is 181.6% (â£Rg-Raâ£/Ra × 100%). It is 3.5 times higher than the original Cu2O nanospheres (52.1%). Moreover, due to the characteristics of high carrier migration rate and excellent conductivity of Ti3C2Tx, the response recovery rate (1062 s/74 s) of Cu2O/Ti3C2Txcomposites is greatly improved than pristine Cu2O (3169 s/293 s). In addition, Cu2O/Ti3C2Txnanocomposites sensor also shows excellent repeatability, outstanding selectivity, and long-term stability. Thus, the Cu2O/Ti3C2Txnanocomposites sensor has broad application prospects for detecting triethylamine gas at room temperature.
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OBJECTIVE: Women with hypothyroidism need to increase exogenous thyroid hormone levels during pregnancy to reduce adverse outcomes. Few studies have reported the effect of gestational levothyroxine (LT4) variations on postpartum LT4 treatment. METHODS: Women were classified as having subclinical hypothyroidism (SCH) (n = 101), overt hypothyroidism (OH) caused by autoimmune thyroiditis (AIT-OH), OH following thyroidectomy for benign thyroid disease (BA-OH) (n = 66), and OH after surgery for papillary thyroid cancer (PTC-OH) (n = 46). Thyroid function was monitored, and LT4 therapy was adjusted accordingly. RESULTS: After delivery, all women with SCH stopped LT4 treatment, and 57.4% of them restarted LT4 treatment in the following 1 year, independently of the gestational LT4 variations. Among patients with OH, after adjusted by gestational body weight, 49.1% of them had LT4 doses less than the prepregnancy dose (baseline) in late pregnancy, leading to LT4 reduction in postpartum. The LT4 dose was reduced to approximately 50% baseline for women with AIT-OH and BA-OH and reduced by 27% for women with PTC-OH. The reduction reasons for AIT-OH and BA-OH were thyroid-stimulating hormone levels of <2.5 mU/L during pregnancy and postpartum thyrotoxicosis occurrence (39.4%), and for PTC-OH, the reason was thyroid-stimulating hormone overinhibition (<1.0 mU/L) before delivery. CONCLUSION: For patients with SCH, postpartum LT4 treatment could initially be suspended. For women with OH, if the LT4 dose in late pregnancy was less than baseline, a prepregnancy dose reduced by 50%, 50%, and 27% should be applied after delivery for women with AIT-OH, BA-OH, and PTC-OH, respectively.
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Hipotireoidismo , Complicações na Gravidez , Neoplasias da Glândula Tireoide , Feminino , Humanos , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/epidemiologia , Período Pós-Parto , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Tireotropina/uso terapêutico , Tiroxina/uso terapêuticoRESUMO
Chemical warfare agents, particularly nerve agents such as sarin, are exceptionally harmful and incredibly perilous to people. Thus, the sensitive detection of these gases is indispensable for reducing the risk of chemical weapons. Herein, we fabricated a room-temperature chemiresistive gas sensor based on two-dimensional few-layer tungsten diselenide (WSe2) nanosheets, which were prepared through a facile liquid-phase exfoliation method. The WSe2-based sensor has demonstrated sensitive and selective detection of dimethyl methylphosphonate (DMMP), which is a well-known simulant of the nerve agent sarin. The sensor based on WSe2 nanosheets revealed a high response reaching 8.91% to 10 ppm DMMP with a fast response time of 100 s. Furthermore, the sensor displayed reliable stability, excellent selectivity, and a low theoretical limit of detection of about 122 ppb. The enhanced sensing performance of WSe2 nanosheets can be ascribed to the increase of the specific surface area, which provides more active adsorption sites for DMMP molecules, thereby facilitating the charge transfer process between DMMP molecules and WSe2 nanosheets. Overall, our results indicate that two-dimensional transition metal dichalcogenide materials have the potential for the design and fabrication of high-performance nerve agent sensing devices.
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Substâncias para a Guerra Química , Compostos Organofosforados , Substâncias para a Guerra Química/análise , Humanos , Temperatura , TungstênioRESUMO
The triterpenes in bitter gourd (Momordica charantia) show a variety of medicinal activities. Oxidosqualene cyclase (OSC) plays an indispensable role in the formation of triterpene skeletons during triterpene biosynthesis. In this study, we identified nine genes encoding OSCs from bitter gourd (McOSC1-9). Analyses of their expression patterns in different tissues suggested that characteristic triterpenoids may be biosynthesized in different tissues and then transported. We constructed a hairy root system in which McOSC7 overexpression led to an increased accumulation of camaldulenic acid, enoxolone, and quinovic acid. Thus, the overexpression of McOSC7 increased the active components content in bitter gourd. Our data provide an important foundation for understanding the roles of McOSCs in triterpenoid synthesis.
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Genoma de Planta , Momordica charantia/genética , Família Multigênica , Ácido Oleanólico/análogos & derivados , Triterpenos/metabolismo , Cromossomos de Plantas/genética , Éxons/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Íntrons/genética , Metaboloma/genética , Metabolômica , Ácido Oleanólico/biossíntese , Filogenia , Raízes de Plantas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transformação GenéticaRESUMO
Lactobacillus has been reported to inhibit acute lung injury (ALI). However, the molecular mechanism of Lactobacillus casei (L. casei) in preventing ALI has not been identified, so we investigated whether L. casei pretreatment could inhibit the activation of TLR4/MyD88/NF-κB signaling pathway following ALI. ALI model was established by intraperitoneal injection of 2 mg/kg lipopolysaccharide (LPS) to female BALB/c mice. In L. casei LC2W group, mice were intragastrically administrated L. casei LC2W for a week, before the ALI modeling. The serum of normal BALB/c mice after intragastric administration of L. casei LC2W was used for in vitro cell assays. The serum was pre-incubated with mouse macrophage cell line (RAW264.7) and human lung cell line (HLF-A), then LPS was added to co-incubate. Compared with ALI model group, L. casei LC2W pretreatment significantly reduced lung pathological damage, the number of neutrophils and total cells in bronchoalveolar lavage fluid. Besides, L. casei LC2W pretreatment could significantly reverse the abnormal expression of ICAM-1, IL-6, TNF-α and IL-10 in lung tissue and serum, plus, L. casei LC2W significantly reduced the phosphorylation levels of IRAK-1 and NF-κB p65. In vitro, the serum decreased the up-regulation of IL-6 and TNF-α in cell lines induced by LPS. In conclusion, L. casei LC2W intragastric administration pretreatment could significantly improve LPS-induced ALI in mice, probably through circulation to reach the lungs so as to inhibit the inflammatory response induced by activation of TLR4/MyD88/NF-κB signaling pathway.
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While continuously developing high-performance chemoresistive gas sensors, reducing device power consumption is not negligible. One of the most efficient ways is to enable gas sensors to work close to room temperature. In this work, we present a gas sensor based on hexagonal tin disulfide (SnS2) nanoplates for sensitive and reversible NO2 sensing at room temperature. Two-dimensional SnS2 nanoplates are synthesized via a facile hydrothermal method using Triton X-100 as a surfactant. The sensor exhibits a high response of 15.6 for 50 ppm NO2 with an experimental limit of detection of 50 ppb at room temperature. Besides, excellent linearity, outstanding selectivity, and reliable long-term stability within 40 d are also demonstrated during the experiment process. The sensing mechanism of this sensor could be explained as the physisorption and charge transfer between NO2 molecules and SnS2 nanoplates, which make it possible for the sensor to work at such a low operating temperature. Our research resulted in a SnS2 nanoplate-based sensor that may pave a new way for effective NO2 detection in the future.
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Molybdenum selenide (MoSe2) has drawn significant interest due to its typical semiconductor properties. MoSe2 is a relatively novel material in the field of gas sensors especially at room temperature. Herein, we utilize a facile and efficient synthetic method of liquid-phase exfoliation to exfoliate bulk MoSe2 into nanosheets. Anhydrous ethanol is used as dispersant, so the low boiling point makes it easy to be removed from MoSe2 nanosheets, which does not affect the subsequent sensing performance. The exfoliated few-layered MoSe2 nanosheets shows significantly enhanced NO2 gas response (1500% to 10 ppm NO2 which is 18 times greater than pristine bulk MoSe2), a low detection concentration (50 ppb), an outstanding repeatability, a remarkable selectivity, and a reliable long-term device durability (more than 60 d) at room temperature (25 °C). The reason of the significant improvement in gas sensing performance can be attributed mainly to the higher surface-to-volume ratio of exfoliated MoSe2 nanosheets. It promotes the adsorption of gas molecules on the surface of the material, thereby facilitating the charge transfer process. The superior performance of this gas sensor makes MoSe2 nanosheets a potential candidate for room temperature NO2 detection.
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Local electric field enhancement is crucial to detect gases for an ionization gas sensor. Nanowires grown collectively along the identical lattice orientation have been claimed to show a strong tip effect in many previous studies. Herein, we propose a novel ionization gas detector structure by using a single crystalline silicon nanowire as one electrode that is placed above the prepatterned nanotips. A significant improvement of the local electric field in its radical direction was obtained leading to an ultralow operation voltage for gas breakdown. Different from the tip of the nanowire in the reported ionization gas sensors, the gaseous discharge current in this device flows towards the sidewall in the case of a trace amount of gas environment change. Technically, this discharge current brings about a sudden temperature rise followed by a fusion of the silicon nanowire. Such unique fusibility of a single nanowire in this gas detection device suggests a novel architecture that is portable and in-site executable and can be used as an integrated gas environmental monitor.
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Current optical-sectioning methods require complex optical system or considerable computation time to improve imaging quality. Here we propose a deep learning-based method for optical sectioning of wide-field images. This method only needs one pair of contrast images for training to facilitate reconstruction of an optically sectioned image. The removal effect of background information and resolution that is achievable with our technique is similar to traditional optical-sectioning methods, but offers lower noise levels and a higher imaging depth. Moreover, reconstruction speed can be optimized to 14 Hz. This cost-effective and convenient method enables high-throughput optical sectioning techniques to be developed.