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A porous cellulose bioreactor with directional channels was prepared for flow catalysis. The hierarchical porous structure enhanced the mass transfer and improved the catalytic efficiency.

Additional file 1: Fig. S1. Flowchart of this study. Fig. S2. Cross-prevalence of pneumonia, asthma, allergic rhinitis and wheezing among preschool children in the Chinese seven cities in 2011 and 2019.

Additional file 2: Tab.S1. Age-specific and age-adjusted prevalence of pneumonia among preschool children in the Chinese seven cities in 2011 and 2019 by gender. Tab.S2. Multiple adjusted odds ratios of pneumonia in the Chinese seven cities of preschool children in 2011 and 2019 by duration of breastfeeding and antibiotics use. Tab. S3. Multiple adjusted odds ratios of asthma, allergic rhinitis and wheezing and in the Chinese seven cities of preschool children in 2011 and 2019. Tab.S4. Age-specific and age-adjusted prevalence of pneumonia among preschool children in the Chinese seven cities in 2011 and 2019 by duration of breastfeeding. Tab. S5. Age-specific and age-adjusted prevalence of pneumonia among preschool children in the Chinese seven cities in 2011 and 2019 by antibiotics use.

Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. As a living biocatalyst, biofilms can stably catalyze the activity of intracellular enzymes. However, it is unclear how boron affects biofilm formation in E. coli, particularly recombinant E. coli with intracellular enzymes. This study screened different boron derivatives to explore their effect on biofilm formation. The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. Results showed that boron derivatives promote AI-2 activity in QS system. After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. Moreover, treatment with H3BO3 (0.6 mM) increased biomass by 88.54%. Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0–0.6 mM H3BO3 and NaBO2 (R2 > 0.8). Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. These findings demonstrated that boron promoted biofilm formation by upregulating the expression levels of biofilm-related genes, improving the QS system AI-2 activity, and increasing EPS secretion in E. coli.

Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. As a living biocatalyst, biofilms can stably catalyze the activity of intracellular enzymes. However, it is unclear how boron affects biofilm formation in

As a nutritious fruit, mulberry is an ideal source of high-quality cyanidin-3-O-glucoside (C

The last decade has witnessed a prosperous development of computational methods and dataset curation for AI-aided drug discovery (AIDD). However, real-world pharmaceutical datasets often exhibit highly imbalanced distribution, which is overlooked by the current literature but may severely compromise the fairness and generalization of machine learning applications. Motivated by this observation, we introduce ImDrug, a comprehensive benchmark with an open-source Python library which consists of 4 imbalance settings, 11 AI-ready datasets, 54 learning tasks and 16 baseline algorithms tailored for imbalanced learning. It provides an accessible and customizable testbed for problems and solutions spanning a broad spectrum of the drug discovery pipeline such as molecular modeling, drug-target interaction and retrosynthesis. We conduct extensive empirical studies with novel evaluation metrics, to demonstrate that the existing algorithms fall short of solving medicinal and pharmaceutical challenges in the data imbalance scenario. We believe that ImDrug opens up avenues for future research and development, on real-world challenges at the intersection of AIDD and deep imbalanced learning., Comment: 29 pages, 7 figures, 8 tables, a machine learning benchmark submission

Retrosynthesis is a major task for drug discovery. It is formulated as a graph-generating problem by many existing approaches. Specifically, these methods firstly identify the reaction center, and break target molecule accordingly to generate synthons. Reactants are generated by either adding atoms sequentially to synthon graphs or directly adding proper leaving groups. However, both two strategies suffer since adding atoms results in a long prediction sequence which increases generation difficulty, while adding leaving groups can only consider the ones in the training set which results in poor generalization. In this paper, we propose a novel end-to-end graph generation model for retrosynthesis prediction, which sequentially identifies the reaction center, generates the synthons, and adds motifs to the synthons to generate reactants. Since chemically meaningful motifs are bigger than atoms and smaller than leaving groups, our method enjoys lower prediction complexity than adding atoms and better generalization than adding leaving groups. Experiments on a benchmark dataset show that the proposed model significantly outperforms previous state-of-the-art algorithms., Comment: 16 pages, 3 figures

Without any scientifically confirmed discoveries to go on, what aliens look like, and the often violent and exploitative behavior and intentions that pop culture ascribes to them, are entirely products of our own imagination. Aliens come from inside ourselves. The Embassy of Aliens is a diplomacy initiative to develop and promote intragalactic tools through which to develop a reimagining of aliens. The first tool to be launched is a musical instrument that facilitates communication between humans and their inner alien. The project hopes to challenge the way we think about the stereotypes, stigmas, and borders we project onto others, societies and worlds. &nbsp

This paper presents an experimental method to investigate the effect of nanomagnetic particle on mechanics performance of magneto-rheological (MR) fluid, including the normal force and shear torque. Under different currents, the mechanics performance of a series of MR fluids with different quantities of nanomagnetic particles (0%, 4%, 7%, 12%, and 16% respectively) are measured by the plate-on-plate shearing test rig. The experimental results indicate that, with an increasing quality percentage of nanomagnetic particles, in a small range of currents (0–1.5 A), the mechanics performances are increasing, but their increment is no longer obvious when the current is above 1.5 A.

Aim: Maintenance hemodialysis (MHD) frequency is associated with survival and complication rates. Achieving the optimal balance between healthcare, quality of life (QOL), and medical costs is challenging. We compared complications, inflammatory status, nutritional status, and QOL between patients with different MHD frequencies. Material and Methods: This was a multicenter randomized trial of patients treated between May 2011 and August 2017 at 3 tertiary hospitals in Wenzhou. Patients were grouped according to their treatment schedule over 1 year: twice-weekly or 3-times-weekly. Complications, biochemistry parameters, and QOL (KDQOL-SFTM 1.3 scale) were assessed. Results: One hundred forty patients were included aged 29 to 68 years (mean age, 50.9 ± 4.3 years). There were no significant differences in infection, heart failure, or cerebral hemorrhage complications between the 2 groups (P = .664). Pre-dialysis hemoglobin, high-sensitivity C-reactive protein, serum albumin, total cholesterol, triglyceride, calcium, phosphate, parathyroid hormone, and ejection fraction were similar in both groups (P > .05). After 1 year of MHD, both groups exhibited significant improvements in these parameters (all P .05), although a difference in BUN was observed between the 2 groups (P

The South China Sea (SCS) is one of the classical example of a non-volcanic passive margin situated within three tectonic plates of the Eurasian, Indo-Australian and Philippine Sea plate. The development of SCS resulted from interaction of various types of plate boundaries, and complex tectonic assemblage of micro blocks and accretionary prisms. Numerous models were proposed for the formation of SCS, yet none can fully satisfy different aspects of tectonic forces. Temporal and geographical reconstruction of Cretaceous and Cenozoic magmatism with the isochrones of major basins was conducted. Our reconstruction indicated the SE margin of Asia had gone through two crustal thinning events. The sites for rifting development are controlled by localized thermal weakening of magmatism. NW–SE extension setting during Late Cretaceous revealed by magmatism distribution and sedimentary basins allow us to allocate the retreated subduction of Pacific plate to the cause of first crustal thinning event. A magmatic gap between 75 and 65 Ma prior to the initiation of first basin rifting suggested a significant modification of geodynamic setting occurred. The Tainan basin, Pearl River Mouth basin, and Liyue basins started to develop since 65 Ma where the youngest Late Cretaceous magmatism concentrated. Sporadic bimodal volcanism between 65 and 40 Ma indicates further continental extension prior to the opening of SCS. The E–W extension of Malay basin and West Natuna began since late Eocene followed by N–S rifting of SCS as Neotethys subducted. The SCS ridge developed between Pearl River Mouth basin and Liyue basin where 40 Ma volcanic activities concentrated. The interaction of two continental stretching events by Pacific followed by Neotethys subduction with localized magmatic thermal weakening is the cause for the non-volcanic nature of SCS.

Visible watermark plays an important role in image copyright protection and the robustness of a visible watermark to an attack is shown to be essential. To evaluate and improve the effectiveness of watermark, watermark removal attracts increasing attention and becomes a hot research top. Current methods cast the watermark removal as an image-to-image translation problem where the encode-decode architectures with pixel-wise loss are adopted to transfer the transparent watermarked pixels into unmarked pixels. However, when a number of realistic images are presented, the watermarks are more likely to be unknown and diverse (i.e., the watermarks might be opaque or semi-transparent; the category and pattern of watermarks are unknown). When applying existing methods to the real-world scenarios, they mostly can not satisfactorily reconstruct the hidden information obscured under the complex and various watermarks (i.e., the residual watermark traces remain and the reconstructed images lack reality). To address this difficulty, in this paper, we present a new watermark processing framework using the conditional generative adversarial networks (cGANs) for visible watermark removal in the real-world application. The proposed method enables the watermark removal solution to be more closed to the photo-realistic reconstruction using a patch-based discriminator conditioned on the watermarked images, which is adversarially trained to differentiate the difference between the recovered images and original watermark-free images. Extensive experimental results on a large-scale visible watermark dataset demonstrate the effectiveness of the proposed method and clearly indicate that our proposed approach can produce more photo-realistic and convincing results compared with the state-of-the-art methods.

PDF/A形式により利用可能, アクセス:WWWによる, 東京外国語大学大学院総合国際学研究科博士 (学術) 論文 (2016年2月), 博甲第206号, 主要参考文献: p173-178, その他のタイトルは英文要旨による

Influence of Mn2+, Mg2+and Ca2+on β-D-glucosidase activity produced byXanthophyllomyces dendrorhouswas measured. The presence of Mn2+could increase the β-D-glucosidase activity and the change in cell morphology of obviously improves the cell growth and the astaxanthin biosynthesis. The cell biomass, the astaxanthin yield and the astaxanthin content in dry cell was reached to 3.65 g L-1, 3.06 mg L-1and 0.84 mg g-1at 72 h of fermentation respectively, which were higher than those in absence of Mn2+.

Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥0.34, p =, Author Summary Plasmodium knowlesi, a parasite of Southeast Asian macaques, has entered the human population. Approximately 10% of P. knowlesi infections are severe, 1–2% are fatal, in Sarawak, Malaysian Borneo. Increase in parasitaemia is associated with disease severity, but little is known about parasite virulence in this newly described human pathogen. Here we present the results of a study on P. knowlesi parasites collected from 147 patients. We use the isolates to produce DNA sequences from a polymorphic (genetically variable) region of two P. knowlesi genes, Pknbpxa and Pknbpxb, that are involved in parasite entry into host red blood cells. We addressed the question that some parasite genotypes may have an invasion advantage leading to severe disease in human infections. We analysed the DNA sequences with matched clinical and laboratory data from the patient cohort (n = 147). We found that specific DNA sequences (Pknbpxa and Pknbpxb alleles) clustered with high parasitaemia and markers of disease severity. Here, for the first time, we provide evidence that variant alleles of the Plasmodium Reticulocyte Binding-Like Protein invasion gene family can influence disease progression in patients with malaria. The biological characteristics of the variants will be studied to aid our understanding of malaria pathophysiology and to inform intervention strategies.

Epidemiological study on strongyloidiasis in humans is currently lacking in Malaysia. Thus, a cross-sectional study was carried out to determine the prevalence of Strongyloides stercoralis infection among the inhabitants of longhouse indigenous communities in Sarawak. A single stool and blood sample were collected from each participant and subjected to microscopy, serological and molecular techniques. Five species of intestinal parasites were identified by stool microscopy. None of the stool samples were positive for S. stercoralis. However, 11% of 236 serum samples were seropositive for strongyloidiasis. Further confirmation using molecular technique on stool samples of the seropositive individuals successfully amplified 5 samples, suggesting current active infections. The prevalence was significantly higher in adult males and tended to increase with age. S. stercoralis should no longer be neglected in any intestinal parasitic survey. Combination of more than 1 diagnostic technique is necessary to increase the likelihood of estimating the ‘true’ prevalence of S. stercoralis.

This study was funded by the Medical Research Council (MRC) UK; Grant number G0801971 and the European Community’s Seventh Framework Programme (FP7/2007-2013), EVIMALAR network of Excellence under grant agreement N° 242095 and NANOMAL under grant agreement N° 304948 Background: Evidence suggests that Plasmodium knowlesi malaria in Sarawak, Malaysian Borneo remains zoonotic, meaning anti-malarial drug resistance is unlikely to have developed in the absence of drug selection pressure. Therefore, adequate response to available anti-malarial treatments is assumed. Methods: Here the ex vivo sensitivity of human P. knowlesi isolates in Malaysian Borneo were studied, using a WHO schizont maturation assay modified to accommodate the quotidian life cycle of this parasite. The in vitro sensitivities of P. knowlesi H strain adapted from a primate infection to in vitro culture (by measuring the production of Plasmodium lactate dehydrogenase) were also examined together with some assays using Plasmodium falciparum and Plasmodium vivax. Results: Plasmodium knowlesi is uniformly highly sensitive to artemisinins, variably and moderately sensitive to chloroquine, and less sensitive to mefloquine. Conclusions: Taken together with reports of clinical failures when P. knowlesi is treated with mefloquine, the data suggest that caution is required if using mefloquine in prevention or treatment of P. knowlesi infections, until further studies are undertaken. Publisher PDF

Background Cytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype of Plasmodium knowlesi infected human erythrocytes to recombinant human ICAM-1, VCAM and CD36. Methods Five patients with PCR-confirmed P. knowlesi malaria were recruited into the study with consent between April and August 2010. Pre-treatment venous blood was washed and cultured ex vivo to increase the proportion of schizont-infected erythrocytes. Cultured blood was seeded into Petri dishes with triplicate areas coated with ICAM-1, VCAM and CD36. Following incubation at 37°C for one hour the dishes were washed and the number of infected erythrocytes bound/mm2 to PBS control areas and to recombinant human ICAM-1 VCAM and CD36 coated areas were recorded. Each assay was performed in duplicate. Assay performance was monitored with the Plasmodium falciparum clone HB3. Results Blood samples were cultured ex vivo for up to 14.5 h (mean 11.3 ± 1.9 h) to increase the relative proportion of mature trophozoite and schizont-infected red blood cells to at least 50% (mean 65.8 ± 17.51%). Three (60%) isolates bound significantly to ICAM-1 and VCAM, one (20%) isolate bound to VCAM and none of the five bound significantly to CD36. Conclusions Plasmodium knowlesi infected erythrocytes from human subjects bind in a specific but variable manner to the inducible endothelial receptors ICAM-1 and VCAM. Binding to the constitutively-expressed endothelial receptor CD36 was not detected. Further work will be required to define the pathological consequences of these interactions.

Compressibility data of RbBr measured by an in situ X-ray energy-dispersive diamond-anvil pressure cell are reported. Measurements of molar volumes were made at room temperature to greater than 15 GPa. The results obtained with a pressure transmitting medium were in agreement with those of previous workers (Bridgman ( 1 ) and Vaidya and Kennedy ( 2 )) using the piston-displacement technique at lower pressures. The results obtained without a pressure transmitting medium, but were probably hydroscopic, were systematically more compressible than those of previous workers. Measurements from this work, combined with Bridgman's ( 1 ) and Vaidya and Kennedy's ( 2 ) piston-displacement measurements to 40,000 kg/cm 2 and 45 kbar, respectively, yielded values of K ° T = 13.84 ± 1.03 GPa and K °′ T = 5.24 ± 0.29.

Background Plasmodium knowlesi malaria causes severe disease in up to 10% of cases in Malaysian Borneo and has a mortality rate of 1 - 2%. However, laboratory markers with the ability to identify patients at risk of developing complications have not yet been assessed as they have for other species of Plasmodium. Methods A case control study was undertaken in two hospitals in Sarikei and Sibu, Malaysian Borneo. One hundred and ten patients with uncomplicated (n = 93) and severe (n = 17) P. knowlesi malaria were studied. Standardized pigment-containing neutrophil (PCN) count, parasite density and platelet counts were determined and analysed by logistic regression and receiver operating characteristic (ROC) analysis. Results The PCN count was strongly associated with risk of disease severity. Patients with high parasite density (≥ 35,000/μl) or with thrombocytopaenia (≤ 45,000/μl) were also more likely to develop complications (odds ratio (OR) = 9.93 and OR = 5.27, respectively). The PCN count yielded the highest area under the ROC curve (AUC) estimate among all markers of severity (AUC = 0.8561, 95% confidence interval: 0.7328, 0.9794). However, the difference between all parameter AUC estimates was not statistically significant (Wald test, p = 0.73). Conclusion Counting PCN is labour-intensive and not superior in predicting severity over parasitaemia and platelet counts. Parasite and platelet counts are simpler tests with an acceptable degree of precision. Any adult patient diagnosed with P. knowlesi malaria and having a parasite count ≥35,000/μl or ≥1% or a platelet count ≤45,000/μl can be regarded at risk of developing complications and should be managed according to current WHO guidelines for the treatment of severe malaria.

P. knowlesi was the first Plasmodium species in which antigenic variation was observed. Variation was due to schizont infected cell agglutination (SICAvar) antigens expressed by the parasite and transported to the exposed surface of the host erythrocyte [1]. PfEMP1 is P. falciparum’s orthologue of P. knowlesi’s SICA proteins [2]. In P. falciparum PfEMP1 is associated with infected erythrocytes binding to receptors such as ICAM-1 expressed on the endothelial cells of the host microvasculature. Here, we use a static protein assay [3] to determine if naturally occurring human P. knowlesi infections can cause erythrocytes to bind to ICAM-1, VCAM-1 and CD36.