RESUMEN
Phage therapy has shown great promise for the treatment of multidrug-resistant bacterial infections. However, the lack of a thorough and organized understanding of phage-body interactions has limited its clinical application. Here, we administered different purified phages (Salmonella phage SE_SZW1, Acinetobacter phage AB_SZ6, and Pseudomonas phage PA_LZ7) intravenously to healthy animals (rats and monkeys) to evaluate the phage-induced host responses and phage pharmacokinetics with different intravenous (IV) doses in healthy animals. The plasma and the organs were sampled after different IV doses to determine the phage biodistribution, phage-induced cytokines, and antibodies. The potential side effects of phages on animals were assessed. A non-compartment model revealed that the plasma phage titer gradually decreased over time following a single dose. Repeated doses resulted in a 2-3 Log10 decline of the plasma phage titer at 5 min compared to the first dose, regardless of the type of phage administered in rats. Host innate immune responses were activated including splenic enlargement following repeated doses. Phage-specific neutralization antibodies in animals receiving phages were detected. Similar results were obtained from monkeys. In conclusion, the mammalian bodies were well-tolerant to the administered phages. The animal responses to the phages and the phage biodistribution profiles could have a significant impact on the efficacy of phage therapy.IMPORTANCEPhage therapy has demonstrated potential in addressing multidrug-resistant bacterial infections. However, an insufficient understanding of phage-host interactions has impeded its broader clinical application. In our study, specific phages were administered intravenously (IV) to both rats and monkeys to elucidate phage-host interactions and evaluate phage pharmacokinetics (PK). Results revealed that with successive IV administrations, there was a decrease in plasma phage concentrations. Concurrently, these administrations elicited both innate and adaptive immune responses in the subjects. Notably, the observed immune responses and PK profiles exhibited variation contingent upon the phage type and the mammalian host. Despite these variations, the tested mammals exhibited a favorable tolerance to the IV-administered phages. This underscores the significance of comprehending these interactions for the optimization of phage therapy outcomes.
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Infecciones Bacterianas , Bacteriófagos , Terapia de Fagos , Animales , Humanos , Ratas , Infecciones Bacterianas/terapia , Bacteriófagos/fisiología , Mamíferos , Fagos Pseudomonas , Distribución Tisular , Farmacorresistencia Bacteriana MúltipleRESUMEN
Platinum-based drugs are widely used in chemotherapy for various types of cancer and are considered crucial. Tetravalent platinum (Pt(IV)) compounds have gained significant attention and have been extensively researched among these drugs. Traditionally, Pt(IV) compounds are reduced to divalent platinum (Pt(II)) after entering cells, causing DNA lesions and exhibiting their anti-tumor effect. However, the available evidence indicates that some Pt(IV) derivatives may differ from the traditional mechanism and exert their anti-tumor effect through their overall structure. This review primarily focuses on the existing literature regarding targeted Pt(II) and Pt(IV) compounds, with a specific emphasis on their in vivo mode of action and the properties of reduction release in multifunctional Pt(IV) compounds. This review provides a comprehensive summary of the design and synthesis strategies employed for Pt(II) derivatives that selectively target various enzymes (glucose receptor, folate, telomerase, etc.) or substances (mitochondria, oleic acid, etc.). Furthermore, it thoroughly examines and summarizes the rational design, anti-tumor mechanism of action, and reductive release capacity of novel multifunctional Pt(IV) compounds, such as those targeting p53-MDM2, COX-2, lipid metabolism, dual drugs, and drug delivery systems. Finally, this review aims to provide theoretical support for the rational design and development of new targeted Pt(IV) compounds.
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Antineoplásicos , Neoplasias , Profármacos , Humanos , Antineoplásicos/farmacología , Sistemas de Liberación de Medicamentos , Platino (Metal)/química , Neoplasias/tratamiento farmacológico , Línea Celular TumoralRESUMEN
The evolving SARS-CoV-2 Omicron strain has repeatedly caused widespread disease epidemics, and effective antibody drugs continue to be in short supply. Here, we identified a batch of nanobodies with high affinity for receptor binding domain (RBD) of SARS-CoV-2 spike protein, separated them into three classes using high performance liquid chromatography (HPLC), and then resolved the crystal structure of the ternary complexes of two non-competing nanobodies (NB1C6 and NB1B5) with RBD using X-ray crystallography. The structures showed that NB1B5 and NB1C6 bind to the left and right flank of the RBD, respectively, and that the binding epitopes are highly conserved cryptic sites in all SARS-CoV-2 mutant strains, as well as that NB1B5 can effectively block the ACE2. These two nanobodies were covalently linked into multivalent and bi-paratopic formats, and have a high affinity and neutralization potency for omicron, potentially inhibiting viral escape. The binding sites of these two nanobodies are relatively conserved, which help guide the structural design of antibodies targeting future variants of SARS-CoV-2 to combat COVID-19 epidemics and pandemics.
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COVID-19 , Anticuerpos de Dominio Único , Humanos , SARS-CoV-2/genética , Anticuerpos , Epítopos/genética , Anticuerpos NeutralizantesRESUMEN
GW117 is new melatonergic antidepressant being developed to show better antidepressant action than agomelatine. The purpose of this study was to evaluate the toxicity and to determine potential target organs after oral (gavage) administration of the test article GW117 for 28 days and to assess the reversibility after a 4-week recovery phase in beagle dogs. Toxicokinetics was also evaluated. Four groups were designed in this study, including the vehicle control group and the GW117 50, 150 and 500 mg/kg/day groups, with 5 dogs/sex/group. Body weight, hematology, clinical chemistry, gross necropsy, organ weight, histopathology, and other indicators were examined. Results showed that animals dosed at ≥150 mg/kg/day showed gastrointestinal reactions (watery feces and dark green/red brown feces), with a dose-response relationship in the incidence and severity grade. Female dogs at 500 mg/kg/day had an increase in organ weight and ratios of the liver at the end of the dosing phase. Histopathology examination showed that some animals at 500 mg/kg/day, especially female animals, had minimal centrilobular hepatocyte hypertrophy in the liver, which reversed after 28-day recovery. With the exception of the above, no GW117-related abnormality was noted. Meanwhile, there were no sexual differences in drug exposure and accumulation after the first and last dosing. The no observed adverse effect dose level (NOAEL) was 150 mg/kg/day, under which mean Cmax and AUC0 â t were 583.5 and 2767.0 ng/ml*h for females and 663.2 and 4046.3 ng/ml*h for males on Day 28.
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Hígado , Masculino , Perros , Animales , Femenino , Toxicocinética , Nivel sin Efectos Adversos ObservadosRESUMEN
Sclareolide is a sesquiterpene lactone isolated from various plant sources in tons every year and is commercially used as a flavor ingredient in the cosmetic and food industries. Antitumor and antiviral activities of sclareolide have been previously reported. However, biological studies of sclareolide synthetic analogous are few. In view of these, we developed a robust synthetic method that allows the assembly of 36 novel sclareolide-indole conjugates and their derivatives. The synthetic method was based on TiCl4-promoted nucleophilic substitution of sclareolide-derived hemiacetal 4, while electron-rich aryles including indoles, polyphenol ethers, and pyrazolo [1,5-a]pyridine were good substrates. The stereochemistry of the final products was confirmed by single-crystal X-ray diffraction analysis, while the antiproliferative activities of selected final products were tested in K562 and MV4-11 cancer cell lines. Cytometric flow analysis shows that lead compounds 8k- and 10-induced robust apoptosis in MV4-11 cancer cells, while they exhibited weak impact on cell cycle progression. Taken together, our study suggests that sclareolide could be a good template and substrate for the synthesis of novel antiproliferative compounds.
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Antineoplásicos , Diterpenos , Antineoplásicos/farmacología , Indoles/química , Diterpenos/farmacología , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Relación Estructura-Actividad , Línea Celular TumoralRESUMEN
Gastrointestinal (GI) diseases, including pathological dysplasia, inflammation, neoplasia and injury, suffer millions of patients globally per year. Organoids, three-dimensional cell mass structures supported by biomaterials in dishes, are currently used as a research model for diseases of the small intestine. However, the traditional enzymatic-digestion method for establishing small-intestinal organoids (EnzyOs) is time consuming and often loses the bulk of crypts, a more efficient and reliable method needs to be developed. In this study, using mouse GI organoids as a model, we formulated a rapid mechanical isolation method that could efficiently isolate and culture villi-crypts into small intestinal organoids (MechOs). Primary duodenum organoids generated by MechOs displayed three types of morphology: spheroid, semi-budding and budding, while EnzyOs produced much less budding. Moreover, primary duodenum organoids from MechOs could be subcultured and presented similar gene expression profiles of small intestine specific markers as that from EnzyOs. Importantly, the MechOs method could also be used to generate other types of organoids derived from the stomach, jejunum-ileum, sigmoid-rectum and bile cysts. Taken together, the results show that MechOs could efficiently and economically generate digestive system organoids, providing a potential basis of epithelial organoids for the clinical treatment of gastroenterological diseases.
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Intestino Delgado , Organoides , Animales , Tracto Gastrointestinal , Humanos , Íleon , Mucosa Intestinal/metabolismo , Ratones , Organoides/metabolismoRESUMEN
Aerosol iron (Fe) solubility is a key factor for the assessment of atmospheric nutrients input to the ocean but poorly specified in models because the mechanism of determining the solubility is unclear. We develop a deep learning model to project the solubility based on the data that we observed in a coastal city of China. The model has five variables: the size range of particles, relative humidity, and the ratios of sulfate, nitrate and oxalate to total Fe (TFe) contents in aerosol particles. Results show excellent statistical agreements with the solubility in the literature over most worldwide seas and margin areas with the Pearson correlation coefficients (r) as large as 0.73-0.97. The exception is the Atlantic Ocean, where good agreement is obtained with the model trained using local data (r: 0.34-0.66). The model further uncovers that the ratio of oxalate/TFe is the most important variable influencing the solubility. These results indicate the feasibility of treating the solubility as a function of the six factors in deep learning models with careful training and validation. Our model and projected solubility provide innovative options for better quantification of air-to-sea input of aerosol soluble Fe in observational and model studies in the global marine atmosphere.
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Atmósfera , Hierro , Aerosoles , Aprendizaje Automático , Oxalatos , SolubilidadRESUMEN
Urine is a major source of reclaimed water and fertilizer. Urine treatment involves two key processes: the recovery of nutrients and the rejection of trace organic compounds (TOrCs). In this study, we investigated the rejection of TOrCs and the recovery of nutrients in human urine using a seawater-driven forward osmosis and membrane distillation (FO-MD) hybrid system. Three 24 h experiments were conducted at draw solution temperatures of 30, 40, and 50 °C. The average rejection rates of cations, anions, and dissolved organic carbon were more than 93.7% and 79.5% in the FO-MD system and FO side, respectively. Ten types of TOrCs were detected in the feed solution, whereas none were detected in the product water, indicating that the TOrCs were completely rejected. The precipitates, i.e., the recovered nutrients in the FO side, were extremely close to magnesium ammonium phosphate (struvite, MgNH4PO4·6H2O), according to their electron microscopic images, elemental composition, and X-ray diffraction spectra, and it was estimated that approximately 85% of the nutrients in the feed solution were recovered. The rejection and recovery efficiencies were unaffected by the draw solution temperature. These results indicate the potential for the sustainable use of FO-MD-based treatments for human urine.
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Destilación , Purificación del Agua , Humanos , Destilación/métodos , Purificación del Agua/métodos , Membranas Artificiales , Ósmosis , Compuestos Orgánicos , Aguas Residuales , Agua , NutrientesRESUMEN
Chemical constituents of water extracts of Asplenium ruprechtii were investigated. Five compounds were isolated by silica gel, Sephadex LH-20 gel column chromatographies and preparative HPLC, and their structures were identified by various spectral analyses as aspleniumside G(1), trans-p-coumaric acid(2), trans-p-coumaric acid 4-O-ß-D-glucoside(3), cis-p-coumaric acid 4-O-ß-D-glucoside(4), and(E)-ferulic acid-4-O-ß-D-glucoside(5). Among them, compound 1 is a new 9,19-cycloartane glycoside.
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Glicósidos , Triterpenos , Cromatografía Líquida de Alta Presión , GlucósidosRESUMEN
Five new cycloartane glycosides, named aspleniumside A - E, were discovered and characterized by re-investigated the remaining extracts of the whole plant of Asplenium ruprechtii Sa. Kurata, a famous folk medicine for treating thromboangitis obliterans in China, Japan, and Korea. Compounds 3-5 possessed the 9,19-seco-cycloartane-9,11-en triterpene aglycone with 3,7(or 23),24,25,30-highly oxidized methylene, methylene or quaternary carbons, that was found in this species for the first time. The stereo-chemistry of all new compounds were fully discussed by extensive analysis of the 1D and 2D NMR data, and comparisons with those data of known compounds. 24R configuration was determined here which indicated the different growing areas of the same species could influence the secondary metabolic behavior, leading to the differences in chemical composition. All glycoside groups were determined as ß-d-glucopyranosyl by 1H coupling constant of anomeric protons and co-TLC of the acid hydrolysate with d-glucose. All the cycloartane glycosides were evaluated against HL-60 and HepG2 cells for cytotoxicity, compounds 1-3, showed potential cytotoxicity with the IC50 in range of 18-60 µM, while the standard sorafenib showed IC50 value of 10.61 ± 0.43 and 13.43 ± 1.12 µM against HL-60 and HepG2, respectively. The results attained in this study indicated that cycloartane glycosides should be the cytotoxicity substance in A. ruprechtii Sa. Kurata, and had the potential to be developed as tumor cytotoxicity agent applied in clinic.
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Antineoplásicos Fitogénicos/farmacología , Helechos/química , Glicósidos/farmacología , Triterpenos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Glicósidos/química , Glicósidos/aislamiento & purificación , Células HL-60 , Células Hep G2 , Humanos , Conformación Molecular , Relación Estructura-Actividad , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
We characterized a new cycloartane glycoside, herein known as aspleniumside F (1), along with five known compounds as kaempferol-3-O-[(6-O-(E)-feruloyl)-ß-D-glucopyranosyl]-(1â2)-ß-D-galacopyranoside (2), quercetin-3-O-[(6-O-(E)-feruloyl)-ß-D-glucopyranosyl]-(1â2)-ß-D-glucopyranoside (3), kaempferol-3-O-[(6-O-(E)-caffeoyl)-ß-D-glucopyranosyl]-(1â2)-ß-D-glucopyranoside (4), kaempferol-3-O-[(6-O-(E)-caffeoyl)-ß-D-glucopyranosyl]-(1â2)-ß-D-glucopyranosyl-7-O-ß-D-glucopyranoside (5), and kaempferol-3-O-[(6-O-p-coumaroyl)-ß-D-glucopyranosyl]-(1â2)-ß-D-glucopyranosyl-7-O-ß-D-glucopyranoside (6), from Asplenium ruprechtii Sa. Kurata, a folk medicine widely used to treat Thromboangiitis obliterans in China, Japan, and Korea. Based on spectroscopic, mainly 1D-, 2D-NMR and (+)-HR-ESI-MS, analyses as well as through comparisons with previous reports, its chemical structure was determined as 3ß,24,30-tri-ß-D-glucopyranosyl-23,25-dihydroxycycloartane (= (23R,24R)-3ß,24-bis-(ß-D-glucopyranosyloxy)-23,25-dihydroxy-9ß-9,19-cyclolanostan-29-yl ß-D-glucopyranoside). According to the 1 H coupling constant of anomeric protons and co-TLC of the acid hydrolysate with D-glucose, all three glycoside groups in 1 were revealed as ß-D-glucopyranosyl. Furthermore, SOD-like antioxidant activity evaluation via IC50 of 12.43, 6.78, 9.12, 6.94 and 4.85â µM revealed that compounds 2-6 had bioactivity.
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Glicósidos/química , Tracheophyta/química , Triterpenos/química , Espectroscopía de Resonancia Magnética con Carbono-13 , Estructura Molecular , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
Traffic vehicles, many of which are powered by port fuel injection (PFI) engines, are major sources of particulate matter in the urban atmosphere. We studied particles from the emission of a commercial PFI-engine vehicle when it was running under the states of cold start, hot start, hot stabilized running, idle and acceleration, using a transmission electron microscope and an energy-dispersive X-ray detector. Results showed that the particles were mainly composed of organic, soot, and Ca-rich particles, with a small amount of S-rich and metal-containing particles, and displayed a unimodal size distribution with the peak at 600â¯nm. The emissions were highest under the cold start running state, followed by the hot start, hot stabilized, acceleration, and idle running states. Organic particles under the hot start and hot stabilized running states were higher than those of other running states. Soot particles were highest under the cold start running state. Under the idle running state, the relative number fraction of Ca-rich particles was high although their absolute number was low. These results indicate that PFI-engine vehicles emit substantial primary particles, which favor the formation of secondary aerosols via providing reaction sites and reaction catalysts, as well as supplying soot, organic, mineral and metal particles in the size range of the accumulation mode. In addition, the contents of Ca, P, and Zn in organic particles may serve as fingerprints for source apportionment of particles from PFI-engine vehicles.
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Conducción de Automóvil , Gasolina/análisis , Material Particulado/análisis , Material Particulado/química , Emisiones de Vehículos/análisis , Contaminación del Aire , Tamaño de la PartículaRESUMEN
In this study, we investigate the rejection of Hg, Cd, and Pb and the effect of coexisting metals on Hg removal through forward osmosis (FO) and membrane distillation (MD) in order to establish a more effective water treatment process. The results of our laboratory experiment indicate that more than 97% of the rejection for each metal is achieved through the FO system, and this rejection is the highest among previous studies using membrane filtrations. Moreover, we examine the matrix effect of the coexisting Cd and Pb on the rejection of Hg in the FO system. Hg2+ rejection increases with increase in the concentration of the coexisting metals. Furthermore, we study the effect of the Hg concentration and the water temperature on rejection of Hg2+. Indeed, the rejection of Hg2+ is achieved above 95% under any condition. However, approximately 1-10 ppb Hg from the feed solution remains in the draw solution due to permeation. Therefore, we use a FO-MD hybrid system. Approximately 100% rejection of Hg2+ and a stable water flux are achieved. Thus, the FO-MD hybrid system is considered an important alternative to previous studies using membrane filtration for heavy metals removal.
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Destilación/métodos , Ósmosis , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Cadmio/química , Plomo/química , Membranas Artificiales , Mercurio/químicaRESUMEN
Rainwater contains substantial bacteria and rain is an efficient pathway for the dissemination of bacteria from the atmosphere to land and water surfaces. However, quantitative information on rainwater bacteria is very limited due to the lack of a reliable method. In this study, the epifluorescence microscopy enumeration with the LIVE/DEAD BacLight Bacterial Viability Kit stain was verified to quantify the abundance of viable and non-viable bacterial cells in rainwater, with the 4',6-diamidino-2-phenylindole (DAPI) stain for the reference of total cell counts. Results showed that the total counts of bacterial cells by LIVE/DEAD BacLight staining were consistent with those by DAPI staining, and the average detection efficiency was (109±29)%. The ratio of cell count with glutaraldehyde fixation to that without fixation was (106±5)% on average. The bacterial concentration in negative control was usually an order of magnitude lower than that in rainwater samples. However, in case of small precipitation, the abundance in negative control could be more than that in rainwater samples. These results indicate that the enumeration with LIVE/DEAD BacLight bacterial viability assay coupled with glutaraldehyde fixation and careful negative control investigation is an approach applicable to the measurement of the concentration and viability of bacterial cells in rainwater.
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Recuento de Colonia Microbiana/métodos , Monitoreo del Ambiente/métodos , Lluvia/microbiología , Microbiología del Agua , Glutaral , Coloración y EtiquetadoRESUMEN
Airborne bacteria were measured when a dust storm passed Beijing in spring 2012 with a focus on cell concentration, viability and TSA- and R2A-cultured strain composition. The concentration varied at an order of 107cells/m3 with dust loading (demonstrated with PM10) and they had a very close correlation (RT2=0.91, p<0.01). At the time of highest PM10 of 652µg/m3, the bacterial concentration reached 1.4×108cells/m3, which was larger than that before and after the dust event by one order. Bacterial viability, the ratio of number concentration of viable cells to total cells, was 32%-64% and smaller in the dust plume than that before the dust arrival. Bacterial strains from the culture ranged between 2.5×104 and 4.6×105CFU/m3 and no correlation with PM10 was determined. Their composition was different before and after the dust arrival according to 16S rRNA gene sequences and strains belong to Actinomycetes and Firmicutes were the majority in the dust samples.
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Microbiología del Aire , Contaminantes Atmosféricos/análisis , Bacterias/clasificación , Monitoreo del Ambiente , Bacterias/genética , Bacterias/aislamiento & purificación , Beijing , Material Particulado/análisisRESUMEN
Dry-deposited particles were collected during the passage of an extremely strong dust storm in March, 2010 at a coastal site in Qingdao (36.15 °N, 120.49 °E), a city located in Eastern China. The size, morphology, and elemental composition of the particles were quantified with a scanning electron microscope equipped with an energy dispersive X-ray instrument (SEM-EDX). The particles appeared in various shapes, and their size mainly varied from 0.4 to 10 µm, with the mean diameters of 0.5, 1.5, and 1.0 µm before, during, and after the dust storm, respectively. The critical size of the mineral particles settling on the surface in the current case was about 0.3-0.4 µm before the dust storm and about 0.5-0.7 µm during the dust storm. Particles that appeared in high concentration but were smaller than the critical size deposited onto the surface at a small number flux. The elements Al, Si and Mg were frequently detected in all samples, indicating the dominance of mineral particles. The frequency of Al in particles collected before the dust storm was significantly lower than for those collected during and after the dust storm. The frequencies of Cl and Fe did not show obvious changes, while those of S, K and Ca decreased after the dust arrival. These results indicate that the dust particles deposited onto the surface were less influenced by anthropogenic pollutants in terms of particle number.
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Polvo/análisis , Material Particulado/análisis , Material Particulado/química , Contaminantes Atmosféricos/análisis , China , Microscopía Electrónica de Rastreo/métodos , Minerales/análisis , Minerales/química , Tamaño de la Partícula , Espectrometría por Rayos X/instrumentaciónRESUMEN
Vertical structures of aerosols from the ground to about 1,000 m altitude in Beijing were measured with a balloon-borne optical particle counter. The results showed that, in hazy days, there were inversions at approximately 500-600 m, below which the particulate matters were well mixed vertically, while the concentration of particles decreased sharply above the mixing layer. Electron microscopic observation of the particles collected with the balloon-borne impactor indicates that the composition of particles is different according to weather conditions in the boundary mixing layer of Beijing city and suggests that dust particles are always dominant in coarse-mode particles. Interestingly, sea-salt particles are frequently identified, suggesting the importance of marine air inflow to the Beijing area even in summer. The Ca-rich spherical particles are also frequently identified, suggesting chemical modification of dust particle by NOx or emission of CaO and others from local emission. Additionally, those types of particles showed higher concentration above the mixing layer under the relatively calm weather condition of summer, suggesting the importance of local-scale convection found in summer which rapidly transported anthropogenic particles above the mixing layer. Lidar extinction profiles qualitatively have good consistency with the balloon-borne measurements. Attenuation effects of laser pulse intensity are frequently observed due to high concentration of particulate matter in the Beijing atmosphere, and therefore quantitative agreement of lidar return and aerosol concentration can be hardly observed during dusty condition. Comparing the depolarization ratio obtained from the lidar measurements with the balloon-borne measurements, the contribution of the dry sea-salt particles, in addition to the dust particles, is suggested as an important factor causing depolarization ratio in the Beijing atmosphere.
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Polvo/análisis , Material Particulado/química , Movimientos del Aire , Beijing , Monitoreo del Ambiente , Microscopía Electrónica de Rastreo , Estaciones del Año , Espectrometría por Rayos X , Tiempo (Meteorología)RESUMEN
Aerosol proteins, as core biological components of bioaerosols, are garnering increasing attention due to their environmental significance, including their roles in atmospheric processes and associated health risks. However, observational data on the proteins are very limited, leaving their distribution and variation in the atmosphere poorly understood. To investigate the long-distance transport of proteins with Asian dust in the Northern Hemisphere middle latitude westerlies to remote downwind areas, we quantified the soluble proteins in aerosol particles, referred to as aerosol soluble proteins (ASPs), collected in the coastal city of Kumamoto, Japan, during the spring of 2023, when three dust events occurred. The concentration of ASPs ranged from 0.22 to 1.68 µg m-3, with an average concentration of 0.73 ± 0.36 µg m-3 under dust conditions and 0.31 ± 0.05 µg m-3 under non-dust conditions. During the dust periods, the largest concentration of ASPs (1.68 µg m-3) coincided with the peak concentration of suspended particulate matter, and the concentration strongly correlated with the mass concentration of particles larger than 2.5 µm, indicating a close dependence of ASPs on dust particles. Primary estimations indicated a dry deposition flux of ASPs at approximately 1.10 ± 0.87 mg m-2 d-1 under the dust conditions. These results prove that Asian dust efficiently transports proteins, facilitating their dispersion in the atmosphere.
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Aerosoles , Contaminantes Atmosféricos , Polvo , Monitoreo del Ambiente , Polvo/análisis , Japón , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Proteínas/análisis , Material Particulado/análisis , Atmósfera/químicaRESUMEN
Aerosol particles in two size ranges, namely 0.18-1.4 µm (fine) and larger than 1.4 µm (coarse), were collected in the pre-dust, in-dust, and post-dust air during the passage of a slowly-moving dust event at a coastal site in southwestern Japan. We identified the composition and size of individual particles using a scanning electron microscope to investigate the variations during dust passage. The particles could be classified as mineral-seasalt mixtures, non-mixture minerals, sulfur-containing minerals, and seasalt particles, and the number fractions of these type particles in the two size ranges exhibited significant variation across the three periods. In the coarse size range, mixture particles accounted for 17.6 %, 26.8 %, and 37.8 % of the particles in the pre-dust, in-dust, and post-dust air, respectively. Non-mixture particles made up 36.8 %, 29.2 %, and 24.3 % in the same respective periods. In the in-dust air, the average relative ratio of sulfur content in sulfur-containing mineral particles in the coarse range was 5.5 %, whereas in the fine range, it was 17.2 %. The aging state of sea salt components, described by the Cl loss and reflecting the changes in particles due to chemical reactions, exhibited significant differences in the two size ranges. In the fine range, the aging of >90 % particles was predominantly influenced by sulfate formation in the in-dust air. In contrast, nitrate likely played a certain role in both the pre-dust and post-dust air. In the coarse range, the aging was independent of sulfate formation. These results indicate the close dependence of the aging of dust particles on their size and the notable variations of the aged states, underscoring the essentiality to treat dust particles properly according to time and space for a better understanding on their roles in the marine atmosphere.
RESUMEN
Epstein-Barr virus (EBV), an oncogenic herpesvirus, is predominantly found in the latent infection form and is highly associated with many human malignancies, which mainly have poor prognoses and no effective treatments. Here, we obtained thirteen compounds from small-molecule libraries for specific inhibition of EBV-latently infected cell growth in vitro by high-throughput screening. Among them, cetrimonium bromide (CetB) was identified to selectively inhibit the growth of different EBV-infected B lymphoma cell lines. Importantly, CetB reduced EBNA1 protein stability, activated G1 arrest and early apoptosis of EBV-latently infected cells without viral lytic reactivation, which leads to dramatically inhibit colony formation and tumor growth of EBV-infected cells in vitro and in vivo, and significantly prolong the survival of tumor-bearing mice. Overall, these findings demonstrate that CetB acts as a highly selective inhibitor of the growth of EBV-infected cells and has the potential for further development of effective therapeutic strategies specific against EBV-associated cancers.