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Vision transformers have achieved remarkable success in computer vision tasks by using multi-head self-attention modules to capture long-range dependencies within images. However, the high inference computation cost poses a new challenge. Several methods have been proposed to address this problem, mainly by slimming patches. In the inference stage, these methods classify patches into two classes, one to keep and the other to discard in multiple layers. This approach results in additional computation at every layer where patches are discarded, which hinders inference acceleration. In this study, we tackle the patch slimming problem from a different perspective by proposing a life regression module that determines the lifespan of each image patch in one go. During inference, the patch is discarded once the current layer index exceeds its life. Our proposed method avoids additional computation and parameters in multiple layers to enhance inference speed while maintaining competitive performance. Additionally, our approach1 requires fewer training epochs than other patch slimming methods.
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Algoritmos , Humanos , Redes Neurales de la Computación , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Particulate matter with an aerodynamic diameter of less than 1 µm (PM1.0) can be extremely hazardous to human health, so it is imperative to accurately estimate the spatial and temporal distribution of PM1.0 and analyze the impact of related policies on it. In this study, a stacking generalization model was trained based on aerosol optical depth (AOD) data from satellite observations, combined with related data affecting aerosol concentration such as meteorological data and geographic data. Using this model, the PM1.0 concentration distribution in China during 2016-2019 was estimated, and verified by comparison with ground-based stations. The coefficient of determination (R2) of the model is 0.94, and the root-mean-square error (RMSE) is 8.49 µg/m3, mean absolute error (MAE) is 4.10 µg/m3, proving that the model has a very high performance. Based on the model, this study analyzed the PM1.0 concentration changes during the heating period (November and December) in the regions where the "coal-to-gas" policy was implemented in China, and found that the proposed "coal-to-gas" policy did reduce the PM1.0 concentration in the implemented regions. However, the lack of natural gas due to the unreasonable deployment of the policy in the early stage caused the increase of PM1.0 concentration. This study can provide a reference for the next step of urban air pollution policy development.
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Contaminantes Atmosféricos , Material Particulado , Material Particulado/análisis , China , Contaminantes Atmosféricos/análisis , Carbón Mineral , Monitoreo del Ambiente , Contaminación del Aire/análisis , Aerosoles/análisisRESUMEN
Listeria monocytogenes is an important foodborne pathogen that causes listeriosis, a severe and fatal condition. Biofilms are communities of microorganisms nested within a self-secreted extracellular polymeric substance, and they protect L. monocytogenes from environmental stresses. Biofilms, once formed, can lead to the persistence of L. monocytogenes in processing equipment and are therefore considered to be a major concern for the food industry. This paper briefly introduces the recent advancements on biofilm formation characteristics and detection methods, and focuses on analysis of the mechanism of L. monocytogenes biofilm resistance; Moreover, this paper also summarizes and discusses the existing different techniques of L. monocytogenes biofilm control according to the physical, chemical, biological, and combined strategies, to provide a theoretical reference to aid the choice of effective control technology in the food industry.
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Listeria monocytogenes , Listeriosis , Humanos , Matriz Extracelular de Sustancias Poliméricas , Biopelículas , Industria de Procesamiento de AlimentosRESUMEN
Remodeling the conductive zone to assist normal myocardial contraction and relaxation during myocardial fibrosis has become the primary concern of myocardial infarction (MI) regeneration. Herein, we report an unbreakable and self-recoverable hyaluronic acid conductive cardiac patch for MI treatment, which can maintain structural integrity under mechanical load and integrate mechanical and electrical conduction and biological cues to restore cardiac electrical conduction and diastolic contraction function. Using the free carboxyl groups and aldehyde groups in the hydrogel system, excellent adhesion properties are achieved in the interface between the myocardial patch and the tissue, which can be closely integrated with the rabbit myocardial tissue, reducing the need for suture. Interestingly, the hydrogel patch exhibits sensitive conductivity (ΔR/R0 ≈ 2.5) for 100 cycles and mechanical stability for 500 continuous loading cycles without collapse, which allows the patch to withstand mechanical damage caused by sustained contraction and relaxation of the myocardial tissue. Moreover, considering the oxidative stress state caused by excessive ROS in the MI area, we incorporated Rg1 into the hydrogel to improve the abnormal myocardial microenvironment, which achieved more than 80% free radicalscavenging efficiency in the local infarcted region and promoted myocardial reconstruction. Overall, these Rg1-loaded conductive hydrogels with highly elastic fatigue resistance have great potential in restoring the abnormal electrical conduction pathway and promoting the myocardial microenvironment, thereby repairing the heart and improving the cardiac function.
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The infection-prone wound pathology microenvironment leads to ulceration and difficult healing of diabetic wounds, which seriously affects the quality of survival of patients. In this study, natural polymer materials gelatin and polylysine were used as substrates. By introducing iron/tannic acid (FeIIITA) composite nanoparticles with excellent photothermal properties into the system, the glutamine residues of gelatin were crosslinked with the primary ammonia of polylysine by glutamine aminotransferase. A nanocomposite hydrogel with excellent antibacterial ability and NO production was constructed it was used to improve the clinical problems of diabetes wounds that were difficult to vascularize and easy to be infected. Under the premise of maintaining its structural stability, the hydrogel can be customized to meet the needs of different mechanical strengths by adjusting the ratios to match different diabetic wounds. Meanwhile, the photothermal effect of FeIIITA nanoparticles can synergize with the endogenous antibacterial ability of polylysine to improve the antibacterial efficacy of hydrogels. The potential of hydrogel to promote intracellular NO production was confirmed by fluorescent staining. Microneedle patches prepared from hydrogel can be applied to diabetic wounds, which can achieve NO deep release. Its anti-inflammatory and angiogenic abilities are also useful in achieving effective healing of diabetic wounds.
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Diabetes Mellitus , Hidrogeles , Humanos , Hidrogeles/farmacología , Hidrogeles/química , Gelatina/química , Polilisina/farmacología , Cicatrización de Heridas , Diabetes Mellitus/tratamiento farmacológico , Antibacterianos/químicaRESUMEN
Endoscopic submucosal dissection (ESD) is one of the most effective approaches for the minimally invasive treatment of early gastrointestinal cancers. Submucosal injections help safely and successfully remove lesions during ESD by elevating the mucosa and separating the submucosal muscle layer. Herein, we report dynamic injectable sodium alginate hydrogels (ISAHs) with shear-thinning for ESD surgery, which were easily fabricated by the sulfhydryl group of GSH-modified sodium alginate (SA-GSH) reacting with the aldehyde group of oxidized sodium alginate (OSA) at room temperature. ISAHs have advantageous self-healing abilities and antioxidant activity. Additionally, according to an in vitro test on porcine colorectal submucosal lifting, the submucosal elevation heights created by ISAHs were 13 % -18 % greater than those created by commercial ESD solutions (0.4 w/v% sodium hyaluronate). These properties and biocompatibility were confirmed in vitro and in vivo experiments. ISAHs will hopefully become a novel submucosal injectable hydrogel to assist ESD surgery.
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Alginatos , Resección Endoscópica de la Mucosa , Porcinos , Animales , Hidrogeles , Mucosa Gástrica/patología , InyeccionesRESUMEN
Chronic wounds, especially diabetic wounds, involve abnormally long inflammatory periods due to their pathological microenvironment of high reactive oxygen species (ROS) levels and lack of blood vessels. Here, via a mild, simple and feasible fabrication approach, a sustained oxygenation system is proposed, consisting of MnO2 nanosheets and a dual-network hydrogel fabricated from natural biomaterials including silk fibroin (SF) and carboxymethyl cellulose (CMC). Compared with the initial value (61.09 kPa), the compression modulus of the dual-network hydrogel increased by 116.2% through the coordination of strong covalent bonds and sacrificial coordination bonds constructed by enzymatic crosslinking and UV-irradiation crosslinking; the intrinsic shear-thinning effect endows the dual-network hydrogel with satisfactory injectable properties to be customized as a predetermined shape to accommodate the irregular wounds of diabetes. The encapsulated MnO2 nanosheets can catalyze the excessive ROS into necessary O2in situ and, after co-incubating with the SF/CMC@MnO2 hydrogels, cells in oxidative stress show significantly lower ROS (3 times) and higher O2 (17 times) levels that are conductive to relieving oxidative stress, promoting angiogenesis and reducing inflammation in vivo. Meanwhile, these SF-based hydrogels can offset the overexpression of matrix metalloproteinases (MMPs) in diabetic wounds (more than 80%) and promote remodeling of the extracellular matrix. Eventually, wound healing rates >76% in 7 days and 100% in 14 days were achieved by the bio-fabricated nanocomposite hydrogel and are remarkably faster than the commercial dressing healing rates (<30% in 7 days and <80% in 14 days). These results indicate that this bio-fabricated hydrogel system with multiple and customizable functions has great promise in the personalized clinical care of chronic wounds.
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Diabetes Mellitus , Fibroínas , Diabetes Mellitus/tratamiento farmacológico , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Compuestos de Manganeso , Nanogeles , Óxidos , Oxígeno , Especies Reactivas de Oxígeno , Cicatrización de HeridasRESUMEN
Although conventional suturing techniques are commonly used in assisting wound closure, they do pose limited conduciveness and may lead to secondary injury to wound tissues. Inspired by marine organism mussels, we designed and manufactured a bio-inspired hydrogel-based bandage with tough wet tissue adhesion to substitute traditional surgical suture, accelerate wound healing and avoid infection. Poly(γ-glutamic acid) was modified with 3,4-dihydroxyphenylalanine and glycidyl methacylate, then introduced into the acrylic acid-co-acrylamide hydrogel matrix with robust mechanical properties. The hydrogel bandage showed strong chemical linkage adhesion (70 ± 2.1 kPa), which is 2.8 times that of commercial tissue adhesive fibrin glue (25 ± 2.2 kPa). The hydrogel bandage can not only maintain the self-stability, but is also capable of self-tuning adhesive strength in the range of 14-70 kPa to achieve different adhesion effects by tuning constituent ratio. The bandage has desirable compression properties (0.7 ± 0.11 MPa) and tensile elongation (about 25 times), which ensures its resistance to damages, especially in joint spaces. Secondly, the bandage was endowed with antioxidant and endogenous broad-spectrum antibacterial properties with its catechol structure. Results also demonstrated excellent cell compatibility and blood compatibility, certifying its eligible biological safety profile. In a rat full-thickness cutaneous deficiency model, we can clearly observe that the bandage possesses the ability to promote wound healing (only need 6 days). Above all, this research provides a new strategy for the emergency treatment of liver hemostasis and myocardial repair during disaster rescue. SUPPLEMENTARY INFORMATION: Experimental details and supporting data are available in the online version of the paper10.1007/s40843-021-1724-8.
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Malaria incidence has declined dramatically over the past decade and China was certified malaria-free in 2021. However, the presence of malaria in border areas and the importation of cases of malaria parasites are major challenges for the consolidation of the achievements made by China. Plasmodium vivax Duffy binding protein (PvDBP) performs a significant role in erythrocyte invasion, and is considered a promising P. vivax vaccine. However, the highly polymorphic region of PvDBP (PvDBP-II) impedes the development of blood-stage vaccine against P. vivax. In this study, we investigated the genetic diversity and natural selection of PvDBP-II among 124 P. vivax isolates collected from the China-Myanmar border (CMB) in Yunnan Province, China, during 2009-2011. To compare genetic diversity, natural selection, and population structure with CMB isolates, 85 pvdbp-II sequences of eastern Myanmar isolates were obtained from GenBank. In addition, global sequences of pvdbp-II were retrieved from GenBank to establish genetic differentiation relationships and networks with the CMB isolates. In total, 22 single nucleotide polymorphisms reflected in 20 non-synonymous and two synonymous mutations were identified. The overall nucleotide diversity of PvDBP-II from the 124 CMB isolates was 0.0059 with 21 haplotypes identified (Hd = 0.91). The high ratio of non-synonymous to synonymous mutations suggests that PvDBP-II had evolved under positive selection. Population structure analysis of the CMB and eastern Myanmar isolates were optimally grouped into five sub-populations (K = 5). Polymorphisms of PvDBP-II display that CMB isolates were genetically diverse. Mutation, recombination, and positive selection promote polymorphism of PvDBP-II of P. vivax population. Although low-level genetic differentiation in eastern Myanmar was identified along with the more effective malaria control measures, the complexity of population structure in malaria parasites has maintained. In conclusion, findings from this study advance knowledge of the understanding of the dynamic of P. vivax population, which will contribute to guiding the rational design of a PvDBP-II based vaccine.
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Initial malarial infection mostly causes symptomatic illness in humans. Infection that is not fatal induces complete protection from severe illness and death, and thus complete protection from severe illness or death is granted with sufficient exposure. However, malaria parasite immunity necessitates constant exposure. Therefore, it is important to evaluate lowered immunity and recurrent susceptibility to symptomatic disease in lower transmission areas. We aimed to investigate selection pressure based on transmission levels, antimalarial drug use, and environmental factors. We whole genome sequenced (WGS) P. falciparum clinical samples from Chinese hosts working in Ghana and compared the results with the WGS data of isolates from native Ghanaians downloaded from pf3k. The P. falciparum samples were generally clustered according to their geographic origin, and Chinese imported samples showed a clear African origin with a slightly different distribution from the native Ghanaian samples. Moreover, samples collected from two host populations showed evidence of differences in the intensity of selection. Compared with native Ghanaian samples, the China-imported isolates exhibited a higher proportion of monoclonal infections, and many genes associated with RBC invasion and immune evasion were found to be under less selection pressure. There was no significant difference in the selection of drug-resistance genes due to a similar artemisinin-based combination therapy medication profile. Local selection of malarial parasites is considered to be a result of differences in the host immunity or disparity in the transmission opportunities of the host. In China, most P. falciparum infections were imported from Africa, and under these circumstances, distinct local selective pressures may be caused by varying acquired immunity and transmission intensity. This study revealed the impact of host switching on the immune system, and it may provide a better understanding of the mechanisms that enable clinical immunity to malaria.
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Antimaláricos , Malaria Falciparum , China , Ghana , Humanos , Plasmodium falciparumRESUMEN
Plasmodium vivax apical membrane antigen-1 (PvAMA-1) is an important vaccine candidate for vivax malaria. However, antigenic variation within PvAMA-1 is a major obstacle to the design of a global protective malaria vaccine. In this study, we analyzed the genetic polymorphism and selection of the PvAMA-1 gene from 152 P. vivax isolates from imported cases to China, collected in the China-Myanmar border (CMB) area in Yunnan Province (YP) during 2009-2011 (n = 71) and 2014-2016 (n = 81), in comparison with PvAMA-1 gene information from Myanmar (n = 73), collected from public data. The overall nucleotide diversity of the PvAMA-1 gene from the 152 YP isolates was 0.007 with 76 haplotypes identified (Hd = 0.958). Results from the population structure suggested three groups among the YP and Myanmar isolates with optimized clusters value of K = 7. In addition, YP (2014-2016) isolates generally lacked some K components that were commonly found in YP (2009-2011) and Myanmar. Meanwhile, PvAMA-1 domain I is found to be the dominant target of positive diversifying selection and most mutation loci were found in this domain. The mutation frequencies of D107N/A, R112K/T, K120R, E145A, E277K, and R438H in PvAMA-1 were more than 70% in the YP isolates. In conclusion, high genetic diversity and positive selection were found in the PvAMA-1 gene from YP isolates, which are significant findings for the design and development of PvAMA-1-based malaria vaccine.
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Antígenos de Protozoos/genética , Variación Genética , Malaria Vivax/parasitología , Proteínas de la Membrana/genética , Plasmodium vivax , Proteínas Protozoarias/genética , China/epidemiología , Malaria Vivax/epidemiología , Mianmar/epidemiología , Plasmodium vivax/genética , Selección Genética , Análisis de Secuencia de ADNRESUMEN
For high-precision measurements of the CO2 column concentration in the atmosphere with airborne integrated path differential absorption (IPDA) Lidar, the exact distance of the Lidar beam to the scattering surface, that is, the length of the column, must be measured accurately. For the high-precision inversion of the column length, we propose a set of methods on the basis of the actual conditions, including autocorrelation detection, adaptive filtering, Gaussian decomposition, and optimized Levenberg-Marquardt fitting based on the generalized Gaussian distribution. Then, based on the information of a pair of laser pulses, we use the direct adjustment method of unequal precision to eliminate the error in the distance measurement. Further, the effect of atmospheric delay on distance measurements is considered, leading to further correction of the inversion results. At last, an airborne experiment was carried out in a sea area near Qinhuangdao, China on March 14, 2019. The results showed that the ranging accuracy can reach 0.9066 m, which achieved an excellent ranging accuracy on 1.57-µm IPDA Lidar and met the requirement for high-precision CO2 column length inversion.
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Communities adjacent to concentrated areas of industrial land use (CAILU) are exposed to elevated levels of pollutants during flood disasters. Many CAILU are also characterized by insufficient infrastructure, poor environmental quality, and socially vulnerable populations. Manchester, TX is a marginalized CAILU neighborhood proximate to several petrochemical industrial sites that is prone to frequent flooding. Pollutants from stormwater runoff discharge from industrial land uses into residential areas have created increased toxicant exposures. Working with local organizations, centers/institutes, stakeholders, and residents, public health researchers sampled air, water, indoor dust, and outdoor soil while researchers from landscape architecture and urban planning applied these findings to develop a community-scaled master plan. The plan utilizes land use and built environment changes to increase flood resiliency and decrease exposure to contaminants. Using a combination of models to assess the performance, costs, and benefits of green infrastructure and pollutant load impacts, the master plan is projected to capture 147,456 cubic feet of runoff, and create $331,400 of annual green benefits by reducing air pollution and energy use, providing pollution treatment, increase carbon dioxide sequestration, and improve groundwater replenishment. Simultaneously, there is a 41% decrease across all analyzed pollutants, reducing exposure to and transferal of toxic materials.
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Ciencia Ciudadana/organización & administración , Planificación de Ciudades/organización & administración , Monitoreo del Ambiente/métodos , Contaminación Ambiental/prevención & control , Inundaciones/prevención & control , Entorno Construido , Sustancias Peligrosas , HumanosRESUMEN
The enzyme FabH catalyzes the initial step of fatty acid biosynthesis that is essential for bacterial survival. Therefore, FabH has been identified as an attractive target for the development of new antibacterial agents. We present here the discovery of a promising new series of Pyrazol-Benzimidazole amides with low toxicity and potent FabH inhibitory. Twenty-seven novel compounds have been synthesized, and all the compounds were characterized by 1H NMR, 13C NMR and MS. Afterwards they were evaluated for in-vitro antibacterial activities against E. coli, P. aeruginosa, B. subtilis and S. aureus, along with E. coli FabH inhibition and cytotoxicity test. Some compounds proved to be of low toxicity and potent, especially compound 31 exhibited the most potential to be a new drug with MIC of 0.49-0.98⯵g/mL against the tested bacterial strains and IC50 of 1.22⯵M against E. coli FabH. Eight analogues 16, 28, 30, 31, 33, 34, 35 and 36 with low range MIC against wild type Xanthomonas Campestris exhibited no inhibition against FabH-deficient mutant strain, which firmly proved the class of compounds arrived at antibacterial activity via interacting with FabH. In silico ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) evaluation also pointed out that these compounds are potential for druggability. Further, effective overall docking scores of all the compounds have been recorded, and docking simulation of compound 31 into E. coli FabH binding pocket has been conducted, where solid binding interactions has been identified.
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Bacillus subtilis/enzimología , Inhibidores Enzimáticos/farmacología , Escherichia coli/enzimología , Acido Graso Sintasa Tipo II/antagonistas & inhibidores , Pseudomonas aeruginosa/enzimología , Staphylococcus aureus/enzimología , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Acido Graso Sintasa Tipo II/genética , Acido Graso Sintasa Tipo II/metabolismo , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Tubulin-targeting drugs have increasingly become the focus of anticancer drugs research. Twenty-five novel benzimidazole grafted benzsulfamide-containing pyrazole ring derivatives were synthesized and evaluated for bioactivity as potential tubulin polymerization inhibitors. Among them, compound 30 showed the most excellent inhibition against tubulin assembly (IC50â¯=â¯1.52⯵M) and in vitro growth inhibitory activity against a panel of four human cancer cell lines (IC50â¯=â¯0.15, 0.21, 0.33 and 0.17⯵M, respectively for A549, Hela, HepG2 and MCF-7). It could also validly induce A549 cell apoptosis, cause cell cycle arrest in G2/M phase and disrupt the cellular microtubule network. These results, along with molecular docking data, provided an important basis for further optimization of compound 30 as a potential anticancer agent.
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Antineoplásicos/farmacología , Bencimidazoles/farmacología , Simulación del Acoplamiento Molecular , Pirazoles/farmacología , Sulfonamidas/farmacología , Moduladores de Tubulina/farmacología , Tubulina (Proteína)/metabolismo , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Bencimidazoles/síntesis química , Bencimidazoles/química , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HEK293 , Hepatocitos/efectos de los fármacos , Humanos , Ratones , Estructura Molecular , Polimerizacion/efectos de los fármacos , Pirazoles/química , Relación Estructura-Actividad , Sulfonamidas/química , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/químicaRESUMEN
A series of new 1-phenylsulphonyl-2-(1-methylindol-3-yl)-benzimidazole derivatives were designed, synthesized and evaluated as potential inhibitors of tubulin polymerization and anthropic cancer cell lines. Among them, compound 33 displayed the most potent tubulin polymerization inhibitory activity in vitro (IC50 = 1.41 µM) and strong antiproliferative activities against A549, Hela, HepG2 and MCF-7 cell lines in vitro with GI50 value of 1.6, 2.7, 2.9 and 4.3 µM, respectively, comparable with the positive control colchicine (GI50 value of 4.1, 7.2, 9.5 and 14.5 µM, respectively) and CA-4 (GI50 value of 2.2, 4.3, 6.4 and 11.4 µM, respectively). Simultaneously, we evaluated that compound 33 could effectively induce apoptosis of A549 associated with G2/M phase cell cycle arrest. Immunofluorescence microscopy also clearly indicated compound 33 a potent antimicrotubule agent. Docking simulation showed that compound 33 could bind tightly with the colchicine-binding site and act as a tubulin inhibitor. Three-dimensional-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent tubulin assembling inhibitory activity in the future.