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BACKGROUND: The accurate determination of iodine in seawater is essential to understanding its impact on the environment and human health. Inductively coupled plasma mass spectrometry (ICP-MS) is a widely used technique for elemental analysis due to its high sensitivity, speed, and low limit of detection (LOD). However, its capability in the detection of iodine in complex matrix samples is still limited by the low sample introduction efficiency of pneumatic nebulization and the high ionization energy of iodine. Dielectric barrier discharge microplasma-induced vapor generation (DBD-µPIVG) is a sample introduction technique that has been widely coupled with atomic spectrometry due to its high vapor generation efficiency, rapid reaction speed, high anti-interference capability, and environmental friendliness. RESULTS: A new method was developed for the rapid and sensitive determination of iodine using DBD-µPIVG coupled with ICP-MS. The DBD-µPIVG sample introduction technique can convert both iodide and iodate to their volatiles with a vapor generation efficiency of 70 %. The experimental conditions were optimized in detail, and the LOD for iodine was 0.04 µg L-1, which was lower compared to pneumatic nebulization and comparable to that after the extraction treatment. The relative standard deviation (RSD) obtained after 11 replicate determinations was 2.4%. Furthermore, the potential mechanism and anti-interference performance of the proposed method were also carefully investigated. SIGNIFICANCE: Compared to other analytical methods for iodine analysis, this approach is environmentally friendly, exhibits high anti-interference capability and enables accurate determination of iodine in complex matrix samples. The high vapor generation efficiency of DBD-µPIVG improves the sensitivity for iodine detection and expands the applicable elemental range of DBD-µPIVG. Finally, the proposed method was successfully applied to analyze the iodine content in seawater samples obtained from the Chinese coastal waters and retains great potential for assessing the distribution of iodine in different sea areas.
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AIMS: It has been reported that some peptides released by the gastro-intestinal tract play important roles in the prevention of myocardial ischemia/reperfusion injury (MIRI). Bombesin (BN) is a biologically active peptide released by non-adrenergic non-cholinergic nerves on the gastric antrum mucosa controlled by the vagus nerve. However, there is a lack of reports on the impact of BN on MIRI. This study aimed to explore the influence of BN on MIRI and its underlying mechanism. MATERIALS AND METHODS: MIRI was induced by either 30â¯min of global ischemia in Langendorff perfused rat hearts, or by ligation of the descending coronary artery for 30â¯min in anesthetized Spraque-Dawley rats, and both were followed by 120â¯min reperfusion. Infarct size and left ventricular function were assessed, and lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) levels were measured spectrophotometrically, while cardiomyocyte apoptosis was detected by TUNEL assay. The content of BN in plasma was measured with enzyme-linked immunosorbent assays (ELISA). The expression of caspase 3, Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were quantified. KEY FINDINGS: BN and vagus nerve stimulation improved cardiac contractile function and reduced myocardial infarct size, attenuated oxidative stress damage and myocardial cell apoptosis, increased the expression of Keap1, Nrf2, and HO-1. and these effects were blocked by using a BN receptor antagonist. SIGNIFICANCE: BN provides protection against MIRI, and its underlying mechanism is through activation of the Keap1/Nrf2/HO-1 pathway. This research provides more reliable evidence for the "gut-heart axis dialogue" and explores potential therapeutic approaches for MIRI.
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Climate change is predicted to increase the occurrence of extreme weather events such as heatwaves, which may thereby impact the outcome of plant-herbivore interactions. While elevated temperature is known to directly affect herbivore growth, it remains largely unclear if it indirectly influences herbivore performance by affecting the host plant they feed on. In this study, we investigated how transient exposure to high temperature influences plant herbivory-induced defenses at the transcript and metabolic level. To this end, we studied the interaction between potato (Solanum tuberosum) plants and the larvae of the potato tuber moth (Phthorimaea operculella) under different temperature regimes. We found that P. operculella larvae grew heavier on leaves co-stressed by high temperature and insect herbivory than on leaves pre-stressed by herbivory alone. We also observed that high temperature treatments altered phylotranscriptomic patterns upon herbivory, which changed from an evolutionary hourglass pattern, in which transcriptomic responses at early and late time points after elicitation are more variable than the ones in the middle, to a vase pattern. Specifically, transcripts of many herbivory-induced genes in the early and late defense stage were suppressed by HT treatment, whereas those in the intermediate stage peaked earlier. Additionally, we observed that high temperature impaired the induction of jasmonates and defense compounds upon herbivory. Moreover, using jasmonate-reduced (JA-reduced, irAOC) and -elevated (JA-Ile-elevated, irCYP94B3s) potato plants, we showed that high temperature suppresses JA signaling mediated plant-induced defense to herbivore attack. Thus, our study provides evidences on how temperature reprograms plant-induced defense to herbivores.
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Resposta ao Choque Térmico , Herbivoria , Larva , Mariposas , Solanum tuberosum , Solanum tuberosum/fisiologia , Solanum tuberosum/parasitologia , Solanum tuberosum/genética , Solanum tuberosum/imunologia , Animais , Mariposas/fisiologia , Larva/fisiologia , Regulação da Expressão Gênica de Plantas , Folhas de Planta/fisiologia , Folhas de Planta/parasitologia , Temperatura Alta , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Defesa das Plantas contra Herbivoria , Transcriptoma , Mudança ClimáticaRESUMO
The urgent need for field detection of uranium in seawater is 2-fold: to provide prompt guidance for uranium extraction and to prevent human exposure to nuclear radiation. However, current methods for this purpose are largely hindered by bulky instrumentation, high costs of developed materials, and severe matrix interferences, which limit their further application in the field. Herein, we demonstrated a portable and label-free strategy for the field detection of uranyl in seawater based on the efficient photocleavage of DNA. Further experiments confirmed the generation of ultraviolet (UV) light-induced reactive oxygen species (ROS), such as O2â¢- and â¢OH, which fragmented oligomeric DNA in the presence of uranyl and UV light. Detailed studies showed that DNA significantly enhances uranyl absorption in the UV-visible region, leading to the generation of more ROS. A fluorescence system for the selective detection of uranyl in seawater was established by immobilizing two complementary oligonucleotides with the fluorescent dye SYBR Green I. The strategy of UV-induced photocleavage offers high selectivity, excellent interference immunity, and high sensitivity for uranyl, with a detection limit of 6.8 nM. Additionally, the fluorescence can be visually detected using a 3D-printed miniaturized device integrated with a smartphone. This method has been successfully applied to the on-site detection of uranyl in seawater in 18 Chinese coastal cities and along the coast of Hainan Island within 3 min for a single sample. The sample testing and field analysis results indicate that this strategy has promising potential for real-time monitoring of trace uranyl in China's coastal waters. It is expected to be utilized for the rapid assessment of nuclear contamination and nuclear engineering construction.
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DNA , Água do Mar , Raios Ultravioleta , Urânio , Água do Mar/análise , Água do Mar/química , DNA/análise , China , Urânio/análise , Corantes Fluorescentes/química , Espécies Reativas de Oxigênio/análise , Limite de Detecção , Processos Fotoquímicos , Diaminas , Benzotiazóis/química , Compostos Orgânicos/análise , Compostos Orgânicos/química , QuinolinasRESUMO
Myelin Basic Protein (MBP) is essential for both elaboration and maintenance of CNS myelin, and its reduced accumulation results in hypomyelination. How different Mbp mRNA levels affect myelin dimensions across the lifespan and how resident glial cells may respond to such changes are unknown. Here, to investigate these questions, we used enhancer-edited mouse lines that accumulate Mbp mRNA levels ranging from 8% to 160% of wild type. In young mice, reduced Mbp mRNA levels resulted in corresponding decreases in Mbp protein accumulation and myelin sheath thickness, confirming the previously demonstrated rate-limiting role of Mbp transcription in the control of initial myelin synthesis. However, despite maintaining lower line specific Mbp mRNA levels into old age, both MBP protein levels and myelin thickness improved or fully normalized at rates defined by the relative Mbp mRNA level. Sheath length, in contrast, was affected only when mRNA levels were very low, demonstrating that sheath thickness and length are not equally coupled to Mbp mRNA level. Striking abnormalities in sheath structure also emerged with reduced mRNA levels. Unexpectedly, an increase in the density of all glial cell types arose in response to reduced Mbp mRNA levels. This investigation extends understanding of the role MBP plays in myelin sheath elaboration, architecture, and plasticity across the mouse lifespan and illuminates a novel axis of glial cell crosstalk.
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Proteína Básica da Mielina , Bainha de Mielina , Neuroglia , RNA Mensageiro , Animais , Proteína Básica da Mielina/metabolismo , Proteína Básica da Mielina/genética , Bainha de Mielina/metabolismo , Bainha de Mielina/genética , RNA Mensageiro/metabolismo , Neuroglia/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MasculinoRESUMO
Circular RNAs (circRNAs) play a critical role in pathological mechanisms of Mycobacterium tuberculosis (Mtb) and can be used as a new biomarker for active tuberculosis (ATB) diagnosis. Therefore, we identified significantly dysregulated circRNAs in ATB patients and healthy controls (HC) and explored their molecular mechanism. We found that hsa_circ_0002371 was significantly up-regulated in PBMCs of ATB patients and Mycobacterium tuberculosis H37Rv- or Mycobacterium bovis bacillus Calmette Guerin (BCG)-infected THP-1 cells. Functional experiments demonstrated that hsa_circ_0002371 inhibited autophagy in BCG-infected THP-1 cells and promoted intracellular BCG survival rate. In terms of mechanism, hsa_circ_0002371 facilitated the expression of hsa-miR-502-5p, as shown by bioinformatics and dual-luciferase reporter gene analysis, respectively. Notably, hsa-miR-502-5p inhibited autophagy via suppressing autophagy related 16 like 1 (ATG16L1) in BCG-infected macrophages and thus promoting intracellular BCG growth. In summation, hsa_circ_0002371 increased the suppression of hsa-miR-502-5p on ATG16L1 and inhibited autophagy to promote Mtb growth in macrophages. In Conclusion, our data suggested that hsa_circ_0002371 was significantly up-regulated in the PBMCs of ATB patients compared with HC. The hsa_circ_0002371/hsa-miR-502-5p/ATG16L1 axis promoted the survival of intracellular Mtb and inhibited autophagy in macrophages. Our findings suggested hsa_circ_0002371 could act as a potential diagnostic biomarker and therapeutic target.
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Proteínas Relacionadas à Autofagia , Autofagia , Macrófagos , MicroRNAs , Mycobacterium tuberculosis , RNA Circular , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , RNA Circular/genética , RNA Circular/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas Relacionadas à Autofagia/genética , Macrófagos/metabolismo , Macrófagos/microbiologia , Células THP-1 , Tuberculose/metabolismo , Tuberculose/microbiologia , Tuberculose/genética , Tuberculose/patologia , Mycobacterium bovis , Masculino , FemininoRESUMO
Preschoolers are notoriously poor at delaying gratification and saving limited resources, yet evidence-based methods of improving these behaviors are lacking. Using the marble game saving paradigm, we examined whether young children's saving behavior would increase as a result of engaging in future-oriented imagination using a storyboard. Participants were 115 typically developing 4-year-olds from a midwestern U.S. metropolitan area (Mage = 53.48 months, SD = 4.14, range = 47-60; 54.8% female; 84.5% White; 7.3% Hispanic/Latino ethnicity; median annual household income = $150,000-$174,999). Children were randomly assigned to one of four storyboard conditions prior to the marble game: Positive Future Simulation, Negative Future Simulation, Positive Routine, or Negative Routine. In each condition, children were asked to imagine how they would feel in the future situation using a smiley face rating scale. Results showed that children were significantly more likely to save (and to save more marbles) in the experimental conditions compared with the control conditions (medium effect sizes). Moreover, imagining saving for the future (and how good that would feel) was more effective at increasing saving behaviors than imagining not saving (and how bad that would feel). Emotion ratings were consistent with the assigned condition, but positive emotion alone did not account for these effects. Results held after accounting for game order and verbal IQ. Implications of temporal psychological distancing and emotion anticipation for children's future-oriented decision making are discussed.
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Imaginação , Humanos , Feminino , Masculino , Pré-Escolar , Comportamento Infantil/psicologia , Desvalorização pelo AtrasoRESUMO
BACKGROUND: The brown planthopper (BPH), Nilaparvata lugens, is one of the most destructive pests of rice. Owing to the rapid adaptation of BPH to many pesticides and resistant varieties, identifying putative gene targets for developing RNA interference (RNAi)-based pest management strategies has received much attention for this pest. The glucoprotein papilin is the most abundant component in the basement membranes of many organisms, and its function is closely linked to development. RESULTS: In this study, we identified a papilin homologous gene in BPH (NlPpn). Quantitative Real-time PCR analysis showed that the transcript of NlPpn was highly accumulated in the egg stage. RNAi of NlPpn in newly emerged BPH females caused nonhatching phenotypes of their eggs, which may be a consequence of the maldevelopment of their embryos. Moreover, the transcriptomic analysis identified 583 differentially expressed genes between eggs from the dsGFP- and dsNlPpn-treated insects. Among them, the 'structural constituent of cuticle' cluster ranked first among the top 15 enriched GO terms. Consistently, ultrastructural analysis unveiled that dsNlPpn-treated eggs displayed a discrete and distorted serosal endocuticle lamellar structure. Furthermore, the hatchability of BPH eggs was also successfully reduced by the topical application of NlPpn-dsRNA-layered double hydroxide nanosheets onto the adults. CONCLUSION: Our findings demonstrate that NlPpn is essential to maintaining the regular structure of the serosal cuticle and the embryonic development in BPH, indicating NlPpn could be a potential target for pest control during the egg stage. © 2024 Society of Chemical Industry.
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Hemípteros , Proteínas de Insetos , Óvulo , Interferência de RNA , Hemípteros/genética , Hemípteros/crescimento & desenvolvimento , Hemípteros/fisiologia , Animais , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Feminino , Técnicas de Silenciamento de GenesRESUMO
Neospora caninum is an obligate intracellular parasite that infects a wide range of mammalian species, and particularly causes abortions in cattle and nervous system dysfunction in dogs. Dense granule proteins (GRAs) are thought to play an important role in the mediation of host-parasite interactions and facilitating parasitism. However, a large number of potential GRAs remain uncharacterized, and the functions of most of the identified GRAs have not been elucidated. Previously, we screened a large number GRAs including NcGRA27 and NcGRA61 using the proximity-dependent biotin identification (BioID) technique. Here, we identified a novel GRA protein NcGRA85 and used C-terminal endogenous gene tagging to determine its localization at the parasitophorous vacuole (PV) in the tachyzoite. We successfully disrupted three gra genes (NcGRA27, NcGRA61 and NcGRA85) of N. caninum NC1 strain using CRISPR-Cas9-mediated homologous recombination and phenotyped the single knockout strain. The NcGRA61 and NcGRA85 genes were not essential for parasite replication and growth in vitro and for virulence during infection of mice, as observed by replication assays, plaque assays and in vitro virulence assays in mice. Deletion of the NcGRA27 gene in the NC1 strain reduced the in vitro replication and growth of the parasite, as well as the pathogenicity of the NC1 strain in mice. In summary, our findings provide a basis for in-depth studies of N. caninum pathogenesis and demonstrate the importance of NcGRA27 in parasite growth and virulence, most likely a new virulence factor of N. caninum.
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Sistemas CRISPR-Cas , Coccidiose , Neospora , Proteínas de Protozoários , Animais , Neospora/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Camundongos , Coccidiose/parasitologia , Coccidiose/veterinária , Feminino , Camundongos Endogâmicos BALB C , Virulência/genética , Técnicas de Inativação de Genes , CãesRESUMO
Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade (ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies (mAbs) are currently available as immune checkpoint inhibitors (ICIs). These ICIs target specific immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Clinical trial results strongly support the feasibility of this immunotherapeutic approach. However, a substantial proportion of patients with cancer develop resistance or tolerance to treatment, owing to tumor immune evasion mechanisms that counteract the host immune response. Consequently, substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1, anti-programmed cell death ligand 1 (anti-PD-L1), and anti-CTLA-4 treatments. Recently, several immune checkpoint molecular targets have been identified, such as T cell immunoreceptor with Ig and ITIM domains (TIGIT), mucin domain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), V-domain immunoglobulin suppressor of T cell activation (VISTA), B and T lymphocyte attenuator (BTLA), and signal-regulatory protein α (SIRPα). Functional mAbs targeting these molecules are under development. CTLA-4, PD-1/PD-L1, and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of research. This review discusses these structures, as well as clinical progress in mAbs targeting these immune checkpoint molecules and their potential applications.
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Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , AnimaisRESUMO
In order to achieve efficient recognition of 3D images and reduce the complexity of network parameters, we proposed a novel 3D image recognition method combining deep neural networks with fractional-order Chebyshev moments. Firstly, the fractional-order Chebyshev moment (FrCM) unit, consisting of Chebyshev moments and the three-term recurrence relation method, is calculated separately using successive integrals. Next, moment invariants based on fractional order and Chebyshev moments are utilized to achieve invariants for image scaling, rotation, and translation. This design aims to enhance computational efficiency. Finally, the fused network embedding the FrCM unit (FrCMs-DNNs) extracts depth features to analyze the effectiveness from the aspects of parameter quantity, computing resources, and identification capability. Meanwhile, the Princeton Shape Benchmark dataset and medical images dataset are used for experimental validation. Compared with other deep neural networks, FrCMs-DNNs has the highest accuracy in image recognition and classification. We used two evaluation indices, mean square error (MSE) and peak signal-to-noise ratio (PSNR), to measure the reconstruction quality of FrCMs after 3D image reconstruction. The accuracy of the FrCMs-DNNs model in 3D object recognition was assessed through an ablation experiment, considering the four evaluation indices of accuracy, precision, recall rate, and F1-score.
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The fruits of Cornus officinalis are used not only as a popular health food to tonify the liver and kidney, but also as staple materials to treat dementia and other age-related diseases. The pharmacological function of C. officinalis fruits with or without seeds is controversial for treating some symptoms in a few herbal prescriptions. However, the related metabolite and pharmacological information between its pericarps and seeds are largely deficient. Here, comparative metabolomics analysis between C. officinalis pericarps and seeds were conducted using an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, and therapeutic effects were also evaluated using several in vitro bioactivity arrays (antioxidant activity, α-glucosidase and cholinesterase inhibitory activities, and cell inhibitory properties). A total of 499 secondary metabolites were identified. Thereinto, 77 metabolites were determined as key differential metabolites between C. officinalis pericarps and seeds, and the flavonoid biosynthesis pathway was identified as the most significantly different pathway. Further, 47 metabolites were determined as potential bioactive constituents. In summary, C. officinalis seeds, which demonstrated higher contents in total phenolics, stronger in vitro antioxidant activities, better α-glucosidase and butyrylcholinesterase inhibitory activities, and stronger anticancer activities, exhibited considerable potential for food and health fields. This work provided insight into the metabolites and bioactivities of C. officinalis pericarps and seeds, contributing to their precise development and utilization.
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Cornus , Frutas , Butirilcolinesterase , alfa-Glucosidases , Sementes , Compostos Fitoquímicos/farmacologiaRESUMO
Millions of people worldwide are affected by naturally occurring arsenic in groundwater. The development of a low-cost, highly sensitive, portable assay for rapid field detection of arsenic in water is important to identify areas for safe wells and to help prioritize testing. Herein, a novel paper-based fluorescence assay was developed for the on-site analysis of arsenic, which was constructed by the solid-phase fluorescence filter effect (SPFFE) of AsH3-induced the generation of silver nanoparticles (AgNPs) toward carbon dots. The proposed SPFFE-based assay achieves a low arsenic detection limit of 0.36 µg/L due to the efficient reduction of Ag+ by AsH3 and the high molar extinction coefficient of AgNPs. In conjunction with a smartphone and an integrated sample processing and sensing platform, field-sensitive detection of arsenic could be achieved. The accuracy of the portable assay was validated by successfully analyzing surface and groundwater samples, with no significant difference from the results obtained through mass spectrometry. Compared to other methods for arsenic analysis, this developed system offers excellent sensitivity, portability, and low cost. It holds promising potential for on-site analysis of arsenic in groundwater to identify safe well locations and quickly obtain output from the global map of groundwater arsenic.
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Iodine is essential for human growth and can enter the body through food, water, and air. Analyzing its presence in the environment is crucial for ensuring healthy human development. However, current large-scale instruments have limitations in the field analysis of iodine. Herein, a miniaturized purge and trap point discharge microplasma optical emission spectrometric (P&T-µPD-OES) device was developed for the field analysis of iodine in water. Volatile iodine molecules were produced from total inorganic iodine (TII) through a basic redox reaction under acidic conditions, then the purge and trap module effectively separated and preconcentrated iodine molecules. The iodine molecules were subsequently atomized and excited by the integrated point discharge microplasma and an iodine atomic emission line at 206.24 nm was monitored by the spectrometer. Under optimal conditions, this proposed method had a detection limit of 16.2 µg L-1 for iodine and a precision better than 4.8%. Besides, the accuracy of the portable device was validated by successful analysis of surface and groundwater samples and a comparison of the mass spectrometry method. This proposed portable, low-power device is expected to support rapid access to iodine levels and distribution in water.
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On the basis of the jet theory of airflow fields and the gas-solid two-phase flow theory, we studied the law of dust migration in a simulated dusting space. We used the control variable method and numerical simulation software to explore the airflow field and dust concentration distribution on the working surface of the dusting under different inlet wind speeds and different attached blades of the double-walled annular air curtain. We determined the speed of the inlet of the annular air curtain to be 30 m/s. When the angle of the attached blade was 30°, the dust concentration of the driver and other workers was controlled below 100 mg/m3, which produced the best dust control effect is the best. Using real data, we built a similar test platform to test the airflow field and dust concentration. Through data measurement and analysis, we proved that a dust control system with a double-wall attached-ring air curtain formed a circulating airflow field that could shield dust and effectively reduce dust concentration in the simulated space. The dust removal efficiency of total dust and exhaled dust reached 98.5% and 97.5%, respectively. We compared the test data and simulation results and concluded that the double-wall attached-ring air curtain could effectively ensure the safety of mine production and provide a better underground working environment for operators.
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Poeira , Vento , Humanos , Poeira/análise , Equipamentos de ProteçãoRESUMO
Based on the production conditions of the 10103 excavation working face of the Baozigou coal mine, this paper analyzes the potential sources of H2S and the expected emission concentrations of H2S in the working face. Considering the previous engineering practice for controlling H2S disasters in coal mine working faces, numerical simulations were conducted to investigate air flow and H2S migration and diffusion in the tunnel in the excavation working face. The migration and distribution of H2S in the coal seam mining face were studied, and the effects of outlet wind speed, duct location, and duct diameter on the H2S concentration distribution were explored. The higher the outlet wind speed, the more conducive to the emission of H2S gas, but too high a wind speed will be detrimental to the concentrated extraction and purification absorption of H2S; the closer the outlet position of the air duct is to the end of the working surface, the lower the H2S concentration in the vortex area at the corner; the air duct If the diameter is too small, the harmful gases released from hard-to-break coal cannot be entrained and taken away. When the diameter of the air duct is too large, the entrainment volume during the jet process will be expanded. To verify the field distribution of H2S concentration at the bottom, middle, and top of the boring machine, a CD4-type portable H2S instrument was used to analyze the distribution of H2S near the excavation working face.
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Detecting scandium (Sc) with high selectivity and sensitivity is a challenging task due to its chemical similarity to other rare earth ions. Our findings show that the fluorescence of the complex fluorescent indicator calcein (CL) is quenched under acidic conditions (pH = 2), and Sc3+ strongly inhibits this process. The results demonstrate that CL forms multimers and precipitates out of the solution under acidic conditions, while Sc3+ causes a significant decrease in the scattering intensity of the solution. Additional experiments revealed that the strong Lewis acid nature of Sc3+ complexes with the carboxyl groups of CL leads to increased dispersion of CL even under acidic conditions, thus enhancing its absorption and fluorescence. The complexation ratio of Sc3+ and CL was investigated through spectral titrations and theoretical calculations. The interaction between Sc3+ and CL is the strongest among rare earth and common metal ions due to the smallest ionic radius, resulting in high selectivity. The fluorescence turn-on strategy had a linear range of 0.04 to 2.25 µM under optimal conditions, with a detection limit of 20 nM for Sc3+. The combination of 3D printing and a smartphone program allows for portable on-site analysis of Sc3+. Mineral and water samples were used to demonstrate the potential of this strategy for the rapid, selective, and sensitive analysis of low levels of Sc3+.
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Although CD19-specific chimeric antigen receptor (CAR) T cells are curative for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), disease relapse with tumor antigen-positive remains a challenge. Cytokine/chemokine-expressing CAR-T cells could overcome a suppressive milieu, but the clinical safety and efficacy of this CAR-T therapy remain unclear. Here we report the preclinical development of CD19-specific CAR-T cells capable of expressing interleukin (IL)-7 and chemokine (C-C motif) ligand (CCL)-19 upon CD19 engagement (referred to as 7 × 19 CAR-T cells) and results from a phase 1 and expansion phase trial of 7 × 19 CAR-T cell therapy in patients with R/R LBCL (NCT03258047). In dose-escalation phase, there were no dose-limiting toxicities observed. 39 patients with R/R LBCL received 7 × 19 CAR-T with doses ranged from 0.5 × 106-4.0 × 106 cells per kg body weight. Grade 3 cytokine release syndrome occurred in 5 (12.8%) patients and ≥ grade 3 neurotoxicity in 4 (10.3%) patients. The overall response rate at 3 months post-single infusion was 79.5% (complete remission, 56.4%; partial response, 23.1%). With a median follow-up of 32 months, the median progression-free survival was 13 months, and median overall survival was not reached, with an estimated rate of 53.8% (95% CI, 40.3% to 72.0%) at two years. Together, these long-term follow-up data from the multicenter clinical study suggest that 7 × 19 CAR-T cells can induce durable responses with a median overall survival of greater than 2 years, and have a manageable safety profile in patients with R/R LBCL.
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Herein, a hybrid substrate for surface-enhanced Raman scattering (SERS) is fabricated, which couples localized surface plasmon resonance (LSPR), charge transfer (CT) resonance, and molecular resonance. Exfoliated 2D TiS2 nanosheets with semimetallic properties accelerate the CT with the tested analytes, inducing a remarkable chemical mechanism enhancement. In addition, the LSPR effect is coupled with a concave gold array located underneath the thin TiS2 nanosheet, providing a strong electromagnetic enhancement. The concave gold array is prepared by etching silicone nanospheres assembled on larger polystyrene nanospheres, followed by depositing a gold layer. The LSPR intensity near the gold layer can be adjusted by changing the layer thickness to couple the molecular and CT resonances, in order to maximize the SERS enhancement. The best SERS performance is recorded on TiS2-nanosheet-coated plasmonic substrates, with a detectable methylene blue concentration down to 10-13 m and an enhancement factor of 2.1 × 109 and this concentration is several orders of magnitude lower than that of the TiS2 nanosheet (10-11 m) and plasmonic substrates (10-9 m). The present hybrid substrate with triple-coupled resonance further shows significant advantages in the label-free monitoring of curcumin (a widely applied drug for treating multiple cancers and inflammations) in serum and urine.