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Heterotopic ossification (HO) is a pathological process that commonly arises following severe polytrauma, characterized by the anomalous differentiation of mesenchymal progenitor cells and resulting in the formation of ectopic bone in non-skeletal tissues. This abnormal bone growth contributes to pain and reduced mobility, especially when adjacent to a joint. Our prior observations suggested an essential role of NGF (Nerve Growth Factor)-responsive TrkA (Tropomyosin Receptor Kinase A)-expressing peripheral nerves in regulating abnormal osteochondral differentiation following tendon injury. Here, we utilized a recently developed mouse model of hip arthroplasty-induced HO to further validate the role of peripheral nerve regulation of traumatic HO. Nerve ingrowth was either modulated using a knockin transgenic animals with point mutation in TrkA, or local treatment with an FDA-approved formulation of long acting Bupivacaine which prevents peripheral nerve growth. Results demonstrate exuberant sensory and sympathetic nerve growth within the peri-articular HO site, and that both methods to reduce local innervation significantly reduced heterotopic bone formation. TrkA inhibition led to a 34% reduction in bone volume, while bupivacaine treatment resulted in a 50% decrease. Mechanistically, alterations in TGFβ and FGF signaling activation accompanied both methods of local denervation, and a shift in macrophages from M1 to M2 phenotypes was observed. In sum, these studies reinforce the observations that peripheral nerves play a role in the etiopathogenesis of HO, and that targeting local nerves represents a potential therapeutic approach for disease prevention. [ABSTRACT FROM AUTHOR]

In this paper, a two-level Newton iterative method is proposed for the stationary micropolar fluid equations. Firstly, the original equations are solved on a coarse grid based on Newton-type linearization. Then, the simplified linearized equations are solved on a fine grid. The stability and error estimates of the method are given in the theoretical part. The results of the theoretical analysis show that when the coarse mesh size H and fine mesh size h satisfy the relation h = O (H 2) , the two-level Newton iterative method can achieve an optimal convergence rate. Finally, the effectiveness and applicability of the method are verified by some numerical experiments. [ABSTRACT FROM AUTHOR]

When Chinese scholars who have obtained doctoral degrees or have undertaken research visits abroad return to work in China, they bring with them transferable experiences, knowledge, and skills acquired overseas. However, they also face challenges with academic reintegration. This study, through 18 semi-structured interviews with returnee scholars, examines the academic reintegration processes of these individuals at Chinese regional universities, focusing on the impact of transnational capital on their reintegration. It highlights the challenges that returnee scholars encounter, such as insufficient resources or a lack of academic infrastructure, and demonstrates how transnational capital can serve as a valuable asset for academic reintegration. This article advocates for a contextualized understanding of the academic reintegration process that considers how the scholars' personal attributes and the environments of their home institutions either facilitate or impede transnational knowledge production. Our findings have implications for the development of policies by the Chinese government and regional universities to support the reintegration of returnee scholars. [ABSTRACT FROM AUTHOR]

Water drives the decay of road subgrades such as frost heave in cold areas and collapse in saline soil areas, which influences the safety and comfort of vehicle transportation. This paper proposes a novel geotechnical material, namely hydrophobized soil, as a subgrade fill material to mitigate water-induced degradation of subgrade. Hydrophobized soil has a low affinity to water and therefore can prevent the subgrade from water infiltration, enhancing the volume stability of subgrades. To demonstrate its feasibility, the hydrophobicity and its durability were investigated in this study. A one-year outdoor weathering test on hydrophobized soil columns was conducted, with the hydrophobicity measured. The results show that hydrophobized sand has different durabilities and exhibits different degradations depending on the chosen hydrophobizing agent and its concentration. Based on the testing results and capillary rise model, the design of hydrophobic hydraulic barrier in subgrade was discussed at the end. [ABSTRACT FROM AUTHOR]

Deep neural networks have shown remarkable performance on a wide range of classification tasks and applications. However, the large model size and the enormous size of the training dataset make the training process slow and often limited by the computing resources. To overcome this limitation, distributed training can be used to accelerate the process by utilizing multiple devices for a single model training. In this work, we evaluate the performance of Microsoft DeepSpeed, a distributed training library, on image classification tasks by comparing the performance of 108 trained neural networks in 27 unique settings. Our experimental results suggest that DeepSpeed may provide limited benefits for simpler learning tasks (e.g. smaller neural network models or simpler datasets). On the other hand, for more complex learning tasks, DeepSpeed can provide up to 8× faster training with possible performance improvement. Our study contributes to a better understanding of the capabilities and limitations of the DeepSpeed library, providing insights into when and where it may be most beneficial to use in image classification settings. [ABSTRACT FROM AUTHOR]

Base editing, the targeted introduction of point mutations into cellular DNA, holds promise for improving genome-scale functional genome screening to single-nucleotide resolution. Current efforts in prokaryotes, however, remain confined to loss-of-function screens using the premature stop codons-mediated gene inactivation library, which falls far short of fully releasing the potential of base editors. Here, we developed a base editor-mediated functional single nucleotide variant screening pipeline in Escherichia coli. We constructed a library with 31,123 sgRNAs targeting 462 stress response-related genes in E. coli, and screened for adaptive mutations under isobutanol and furfural selective conditions. Guided by the screening results, we successfully identified several known and novel functional mutations. Our pipeline might be expanded to the optimization of other phenotypes or the strain engineering in other microorganisms. [ABSTRACT FROM AUTHOR]

Background: The clinical efficacy and safety of intravenous immunoglobulin (IVIg) treatment for COVID-19 remain controversial. This study aimed to map the current status and gaps of available evidence, and conduct a meta-analysis to further investigate the benefit of IVIg in COVID-19 patients. Methods: Electronic databases were searched for systematic reviews/meta-analyses (SR/MAs), primary studies with control groups, reporting on the use of IVIg in patients with COVID-19. A random-effects meta-analysis with subgroup analyses regarding study design and patient disease severity was performed. Our outcomes of interest determined by the evidence mapping, were mortality, length of hospitalization (days), length of intensive care unit (ICU) stay (days), number of patients requiring mechanical ventilation, and adverse events. Results: We included 34 studies (12 SR/MAs, 8 prospective and 14 retrospective studies). A total of 5571 hospitalized patients were involved in 22 primary studies. Random-effects meta-analyses of very low to moderate evidence showed that there was little or no difference between IVIg and standard care or placebo in reducing mortality (relative risk [RR] 0.91; 95% CI 0.78–1.06; risk difference [RD] 3.3% fewer), length of hospital (mean difference [MD] 0.37; 95% CI − 2.56, 3.31) and ICU (MD 0.36; 95% CI − 0.81, 1.53) stays, mechanical ventilation use (RR 0.92; 95% CI 0.68–1.24; RD 2.8% fewer), and adverse events (RR 0.98; 95% CI 0.84–1.14; RD 0.5% fewer) of patients with COVID-19. Sensitivity analysis using a fixed-effects model indicated that IVIg may reduce mortality (RR 0.76; 95% CI 0.60–0.97), and increase length of hospital stay (MD 0.68; 95% CI 0.09–1.28). Conclusion: Very low to moderate certainty of evidence indicated IVIg may not improve the clinical outcomes of hospitalized patients with COVID-19. Given the discrepancy between the random- and fixed-effects model results, further large-scale and well-designed RCTs are warranted. [ABSTRACT FROM AUTHOR]

Gut dysbiosis has been identified as a crucial factor of Alzheimer's disease (AD) development for apolipoprotein E4 (APOE4) carriers. Inulin has shown the potential to mitigate dysbiosis. However, it remains unclear whether the dietary response varies depending on sex. In the study, we fed 4-month-old APOE4 mice with inulin for 16 weeks and performed shotgun metagenomic sequencing to determine changes in microbiome diversity, taxonomy, and functional gene pathways. We also formed the same experiments with APOE3 mice to identify whether there are APOE-genotype dependent responses to inulin. We found that APOE4 female mice fed with inulin had restored alpha diversity, significantly reduced Escherichia coli and inflammation-associated pathway responses. However, compared with APOE4 male mice, they had less metabolic responses, including the levels of short-chain fatty acids-producing bacteria and the associated kinases, especially those related to acetate and Erysipelotrichaceae. These diet- and sex- effects were less pronounced in the APOE3 mice, indicating that different APOE variants also play a significant role. The findings provide insights into the higher susceptibility of APOE4 females to AD, potentially due to inefficient energy production, and imply the importance of considering precision nutrition for mitigating dysbiosis and AD risk in the future. [ABSTRACT FROM AUTHOR]

Background: The progestin and adipoQ receptors (PAQRs) family contains 11 genes involved in the regulation of metabolism and cancer development. However, a comprehensive understanding of the role of PAQRs in cancer remains largely scarce, and the associations between their expression levels and immune signatures also need to be researched. Methods: Here, we applied pan-cancer analysis to explore the associations between PAQRs expression and survival, tumor microenvironment (TME), and drug sensitivity from the UCSC Xena and CellMiner databases. Besides, we further studied the expression, survival and somatic mutations of PAQRs in lung cancer (LC) from TCGA database. Results: The results showed that PAQRs had significant heterogeneity with some upregulation and some downregulation in most tumors. Specifically, compared with PAQR3/5/6/9 and MMD2, ADIPOR1/2, PAQR4/7/8 and MMD had higher levels of average expression in all tumor types. PAQRs expression was greatly correlated with survival, immune subtypes, TME, and drug sensitivity. Furthermore, this research concentrated on analyzing the relationship of PAQRs expression with LC prognosis, and proved that ADIPOR2, PAQR4/9 and MMD were independent prognostic factors for LC patients. Finally, based on somatic mutation data, the genetic mutations in LC patients were majorly missense mutations, and TP53 and TTN had the top two highest mutation frequencies. Conclusion: Collectively, PAQRs may serve as robust biomarkers to predict the prognosis and guide immunotherapy of tumors, especially LC, which enables novel ways for improving cancer treatment. [ABSTRACT FROM AUTHOR]

Purpose: Available evidence indicates that dipyridamole enhances the anti-thrombotic effects of aspirin for the prevention of secondary strokes. Aspirin is a well-known non-steroid anti-inflammatory drug. This anti-inflammatory property has turned aspirin into a potential drug for inflammation-related cancers such as colorectal cancer (CRC). Here, we aimed to explore whether the anti-cancer effect of aspirin against CRC could be improved by combined administration with dipyridamole. Methods: Population-based clinical data analysis was conducted to assess a possible therapeutic effect of combined dipyridamole and aspirin treatment in inhibiting CRC compared with either monotherapy. This therapeutic effect was further verified in different CRC mouse models, i.e. an orthotopic xenograft mouse model, an AOM/DSS mouse model, an Apcmin/+ mouse model and a patient derived xenograft (PDX) mouse model. The in vitro effects of the drugs on CRC cells were tested using CCK8 and flow cytometry assays. RNA-Seq, Western blotting, qRT-PCR and flow cytometry were used to identify the underlying molecular mechanisms. Results: We found that dipyridamole combined with aspirin had a better inhibitory effect on CRC than either monotherapy alone. The enhanced anti-cancer effect of the combined use of dipyridamole with aspirin was found to rely on the induction of an overwhelmed endoplasmic reticulum (ER) stress and subsequent pro-apoptotic unfolded protein response (UPR), which was different from the anti-platelet effect. Conclusions: Our data indicate that the anti-cancer effect of aspirin against CRC may be enhanced by combined administration with dipyridamole. In case further clinical studies confirm our findings, these may be repurposed as adjuvant agents. [ABSTRACT FROM AUTHOR]

Heterotopic ossification (HO) is a pathological process resulting in aberrant bone formation and often involves synovial lined tissues. During this process, mesenchymal progenitor cells undergo endochondral ossification. Nonetheless, the specific cell phenotypes and mechanisms driving this process are not well understood, in part due to the high degree of heterogeneity of the progenitor cells involved. Here, using a combination of lineage tracing and single-cell RNA sequencing (scRNA-seq), we investigated the extent to which synovial/tendon sheath progenitor cells contribute to heterotopic bone formation. For this purpose, Tppp3 (tubulin polymerization-promoting protein family member 3)-inducible reporter mice were used in combination with either Scx (Scleraxis) or Pdgfra (platelet derived growth factor receptor alpha) reporter mice. Both tendon injury- and arthroplasty-induced mouse experimental HO models were utilized. ScRNA-seq of tendon-associated traumatic HO suggested that Tppp3 is an early progenitor cell marker for either tendon or osteochondral cells. Upon HO induction, Tppp3 reporter+ cells expanded in number and partially contributed to cartilage and bone formation in either tendon- or joint-associated HO. In double reporter animals, both Pdgfra+Tppp3+ and Pdgfra+Tppp3- progenitor cells gave rise to HO-associated cartilage. Finally, analysis of human samples showed a substantial population of TPPP3-expressing cells overlapping with osteogenic markers in areas of heterotopic bone. Overall, these data demonstrate that synovial/tendon sheath progenitor cells undergo aberrant osteochondral differentiation and contribute to HO after trauma. [ABSTRACT FROM AUTHOR]

Purpose: Few data are available regarding the nephrotoxicity of immune checkpoint inhibitor (ICI) combination therapy in advanced renal cell carcinoma (RCC). This study aimed to investigate the nephrotoxicity of ICI-based combination therapy versus standard of care sunitinib in patients with advanced RCC. Methods: We searched Embase/PubMed/Cochrane Library for relevant randomized controlled trials (RCTs). Treatment-related nephrotoxicities including increase of creatinine and proteinuria were analyzed by Review Manager 5.4 software. Results: Seven RCTs involving 5239 patients were included. The analysis showed that ICI combination therapy had similar risks of any grade (RR = 1.03, 95% CI: 0.77–1.37, P = 0.87) and grade 3–5 (RR = 1.48, 95% CI: 0.19–11.66, P = 0.71) increased creatinine compared with sunitinib monotherapy. However, ICI combination therapy was associated with significantly higher risks of any grade (RR = 2.33, 95% CI: 1.54–3.51, P < 0.0001) and grade 3–5 proteinuria (RR = 2.25, 95% CI: 1.21–4.17, P = 0.01). Conclusions: This meta-analysis suggests that ICI combination therapy shows more nephrotoxicity of proteinuria than sunitinib in advanced RCC, which deserves a high attention in the clinic. [ABSTRACT FROM AUTHOR]

The development of donor-acceptor (D-A) type conjugated polymers depends largely on the design of novel A building blocks. Herein, we report a novel A building block based on the cyano-substituted organoboron unit (SBN-3). Compared with the most common fluorine-substituted B←N unit, SBN-3 displays a significantly downshifted LUMO energy level because of the strong electron-withdrawing ability of cyano groups. In addition, due to the greater impact of cyano substitution on LUMO than on HOMO, SBN-3 exhibits a reduced band gap, near-infrared absorption and fluorescence properties. The D-A type conjugated polymers based on the cyano-substituted B←N unit with thiophene-based units show narrow optical band gaps of ca. 1.3 eV as well as distinctive electronic structures, i.e., delocalized LUMOs and localized HOMOs. This work thus provides not only an effective approach to design strong A units but also a new electron-deficient building block for D-A type conjugated polymers. [ABSTRACT FROM AUTHOR]

N,N-Dimethylformamide (DMF), a nitrogen-containing volatile organic compound (NVOC) with high emissions from the spray industry, has attracted increasing attention. In this study, Cu-ZSM-5 catalysts with different CuO particle sizes of 3, 6, 9 and 12 nm were synthesized and tested for DMF selective catalytic oxidation. The crystal structure and physicochemical properties of the catalyst were studied by various characterization methods. The catalytic activity increases with increasing CuO particle size, and complete conversion can be achieved at 300–350 °C. The Cu-12 nm catalyst has the highest catalytic activity and can achieve complete conversion at 300 °C. The Cu-6 nm sample has the highest N2 selectivity at lower temperatures, reaching 95% at 300 °C. The activity of the catalysts is determined by the surface CuO cluster species, the bulk CuO species and the chemisorbed surface oxygen species. The high N2 selectivity of the catalyst is attributed to the ratio of isolated Cu2+ and bulk CuO species, and weak acidity is beneficial to the formation of N2. The results in this work will provide a new design of NVOC catalytic oxidation catalysts. [ABSTRACT FROM AUTHOR]

Interest in the identification of thermostable lipases for industrial applications is growing. Herein, the novel thermostable lipase TDL2 was identified from the thermophilic fungus Thermomyces dupontii ATCC 16461 and its gene was cloned and overexpressed in Pichia pastoris. The recombinant TDL2 was purified and biochemically characterized. The optimal conditions for hydrolytic activity were identified as 50 °C and pH 8.5. Interestingly, the enzyme was stable at 50 °C and stable over the pH range of 6.5–9.0. Additionally, the activity analysis for various p-nitrophenyl acyl esters indicated that the lipase TDL2 showed higher specific activity for medium- and long-chain substrates, as well as the highest activity toward p-nitrophenyl laurate. Furthermore, the lipase TDL2 exhibited excellent enantioselectivity (E > 200) in the kinetic resolution of 2-carboxyethyl-3-cyano-5-methylhexanoic acid ethyl ester. Given the excellent enantioselectivity, TDL2 is an interesting enzyme for industrial applications. [ABSTRACT FROM AUTHOR]

The H5N8 avian influenza viruses have been widely circulating in wild birds and are responsible for the loss of over 33 million domestic poultry in Europe, Russia, Middle East, and Asia since January 2020. To monitor the invasion and spread of the H5N8 virus in China, we performed active surveillance by analyzing 317 wild bird samples and swab samples collected from 41,172 poultry all over the country. We isolated 22 H5N8 viruses from wild birds and 14 H5N8 viruses from waterfowls. Genetic analysis indicated that the 36 viruses formed two different genotypes: one genotype viruses were widely detected from different wild birds and domestic waterfowls; the other genotype was isolated from a whopper swan. We further revealed the origin and spatiotemporal spread of these two distinct H5N8 virus genotypes in 2020 and 2021. Animal studies indicated that the H5N8 isolates are highly pathogenic to chickens, mildly pathogenic in ducks, but have distinct pathotypes in mice. Moreover, we found that vaccinated poultry in China could be completely protected against H5N8 virus challenge. Given that the H5N8 viruses are likely to continue to spread in wild birds, vaccination of poultry is highly recommended in high-risk countries to prevent H5N8 avian influenza. [ABSTRACT FROM AUTHOR]

Pichia pastoris has gained much attention as a popular microbial cell factory for the production of recombinant proteins and high-value chemicals from laboratory to industrial scale. However, the lack of convenient and efficient genome engineering tools has impeded further applications of Pichia pastoris towards metabolic engineering and synthetic biology. Here, we report a CRISPR-based toolbox for gene editing and transcriptional regulation in P. pastoris. Based on the previous attempts in P. pastoris, we constructed a CRISPR/Cas9 system for gene editing using the RNA Pol-III–driven expression of sgRNA. The system was used to rapidly recycle the selectable marker with an eliminable episomal plasmid and achieved up to 100% knockout efficiency. Via dCas9 fused with transcriptional repressor (Mix1/RD1152) or activator (VPR), a flexible toolbox for regulation of gene expression was developed. The reporter gene eGFP driven by yeast pGAP or pCYC1 promoter showed strong inhibition (above 70%) and up to ~ 3.5-fold activation. To implement the combinatorial genetic engineering strategy, the CRISPR system contained a single Cas9-VPR protein, and engineered gRNA was introduced in P. pastoris for simultaneous gene activation, repression, and editing (CRISPR-ARE). We demonstrated that CRISPR-ARE was highly efficient for eGFP activation, mCherry repression, and ADE2 disruption, individually or in a combinatorial manner with a stable expression of multiplex sgRNAs. The simple and multifunctional toolkit demonstrated in this study will accelerate the application of P. pastoris in metabolic engineering and synthetic biology. Key points: • An eliminable CRISPR/Cas9 system yielded a highly efficient knockout of genes. • Simplified CRISPR/dCas9-based tools enabled transcriptional regulation of targeted genes. • CRISPR-ARE system achieved simultaneous gene activation, repression, and editing in P. pastoris. [ABSTRACT FROM AUTHOR]

Methylene blue (MB) is one of the most common cationic dyes to detect heparin. As the sulfate residue presented in heparin was the main contributor to bind with MB, the UV performance of the MB with selectively desulfated heparin derivatives was investigated. It was found that the sulfate residue in different heparin analogues did not show the equal ability to attract MB binding. The stoichiometry of sulfate with MB among the heparin and derivatives was verified as a non-constant number. For the two selectively desulfated heparin derivatives: sulfate elimination at 6-O (6-OdeS) and N-acetylated heparin (N-deS-Acetyl), the MB to sulfate ratios were significantly higher than for heparin. For the not fully diminished sulfate at 2-O heparin derivative (2-OdeS), the MB-SO3- ratio of 2-OdeS was between 6-OdeS, N-deS-Acetlyl and heparin. Although in a distinct sulfation position, the MB-SO3- ratio of 6-OdeS and N-deS-Acetyl was almost equal, which agreed with the comparable total desulfation degree between 6-OdeS and N-deS-Acetyl. In addition, compared to heparin groups, the non-desulfated gs-HP showed no significantly different MB-SO3- ratio with heparin. The above results demonstrated that compared with the sulfate location and glycan composition of heparin, the content of sulfate was the most essential factor for the MB binding. [ABSTRACT FROM AUTHOR]

Mixotrophic bacteria provide a desirable alternative to the use of classical heterotrophic or chemolithoautotrophic bacteria in environmental technology, particularly under limiting nutrients conditions. Their bi-modal ability of adapting to inorganic or organic carbon feed and sulfur, nitrogen, or even heavy metal stress conditions are attractive features to achieve efficient bacterial activity and favorable operation conditions for the environmental detoxification or remediation of contaminated waste and wastewater. This review provides an overview on the state of the art and summarizes the metabolic traits of the most promising and emerging non-model mixotrophic bacteria for the environmental detoxification of contaminated wastewater and waste containing excess amounts of limiting nutrients. Although mixotrophic bacteria usually function with low organic carbon sources, the unusual capabilities of mixotrophic electroactive exoelectrogens and electrotrophs in bioelectrochemical systems and in microbial electrosynthesis for accelerating simultaneous metabolism of inorganic or organic C and N, S or heavy metals are reviewed. The identification of the mixotrophic properties of electroactive bacteria and their capability to drive mono- or bidirectional electron transfer processes are highly exciting and promising aspects. These aspects provide an appealing potential for unearthing new mixotrophic exoelectrogens and electrotrophs, and thus inspire the next generation of microbial electrochemical technology and mixotrophic bacterial metabolic engineering. Key points: • Mixotrophic bacteria efficiently and simultaneously remove C and N, S or heavy metals. • Exoelectrogens and electrotrophs accelerate metabolism of C and N, S or heavy metals. • New mixotrophic exoelectrogens and electrotrophs should be discovered and exploited. [ABSTRACT FROM AUTHOR]

Various peptides with inhibitory activity against human dipeptidyl peptidase-IV (hDPP-IV), which degrades glucagon-like peptide 1 (GLP-1) and decreases insulin release, were isolated from synthetic tripeptide mixtures, having sequences Val-Pro-Xaa (VPX) or Ile-Pro-Xaa (IPX). All peptides isolated by reversed-phase high performance liquid chromatography (HPLC) analysis were measured for hDPP-IV inhibitory activity. VPV and VPI prepared from the VPX mixture and IPI isolated from the IPX mixture, showed the highest hDPP-IV inhibitory activity. The dissociation constants for hDPP-IV and IC50 values of the peptides were analyzed to understand the reason for the potent inhibitory activity of these tripeptides. The IC50 and Ki values of VPV, VPI, and IPI were found to be 20.2, 22.2, and 46.7 µM and 10.8, 11.3 and 21.4 M−1, respectively. Further, degradation of the peptides by the proteolytic action of hDPP-IV was analyzed to understand the stability of these peptides. Peptides with lower Ki and IC50 values showed relatively slower degradation when incubated with hDPP-IV. These results suggested that a peptide might have higher hDPP-IV inhibitory activity because of its higher affinity and stronger resistance to hDPP-IV, which is caused by the introduction of a hydrophobic amino acid at the C-terminal end of its VP or IP sequence. [ABSTRACT FROM AUTHOR]

Academic books are an important carrier of knowledge for scientific communication. This study aims to gain an improved understanding of academic books by jointly analyzing the altmetric and citation indicators. We explore the impact of academic books among six fields. The data set includes 666,527 records of the Book Citation Index from Web of Science in 2013–2017. Results reveal as follows. (1) The coverage of digital object identifiers and altmetric values on books was relatively low. (2) The impact of books shows evident disciplinary differences in the citation and altmetric indicators. Clinical, Pre-Clinical and Health books had the highest altmetric impact but the lowest citation impact. However, Physical Sciences books showed the opposite traits. Although books are the preferred publication format of the fields of Arts and Humanities; and Social Sciences, the performance of the book impact based on the citation and altmetric indicators was not apparent among six fields. Overall, Social Sciences have relatively better performance than Arts and Humanities. (3) The citation frequency of early publications is significantly higher than that of recent publications, whereas the altmetric attention score presented a growth trend and the cumulative effect is not evident. The clear but weak correlations between altmetric indicators and citations of books were also found. (4) The hierarchical cluster analysis of fields based on the citation and altmetric indicators revealed that the fields of Clinical, Pre-Clinical and Health; and Life Sciences showed high internal homogeneity. However, the fields of Social Sciences, Arts and Humanities are heterogeneous. This study is a constructive attempt to show the macroscopic traits of academic books. Altmetric indexes were involved in multidisciplinary comparison analysis to enhance the understanding of books. [ABSTRACT FROM AUTHOR]

A cobalt-based hydrotalcite-like compound was prepared using a constant-pH coprecipitation method. Cobalt-transition metal oxides (Co2XAlO, X = Co, Mg, Ca and Ni) were investigated for the deep catalytic oxidation of o-chlorophenol as a typical heteroatom contaminant containing chlorine atoms. The partial substitution of Co by Mg, Ca or Ni in the mixed oxide can promote the catalytic oxidation of o-chlorophenol. The Co2MgAlO catalyst presented the best catalytic activity, and could maintain 90% o-chlorophenol conversion at 167.1°C, compared only 27% conversion for the Co3AlO catalyst. The results demonstrated that the high activity could be attributed to its increased low-temperature reducibility, rich active oxygen species and excellent oxygen mobility. In the existence of acid and base sites, catalysts with strong basicity also showed preferred activity. The organic by-products generated during the o-chlorophenol catalytic oxidation over Co2MgAlO catalyst included carbon tetrachloride, trichloroethylene, 2,4-dichlorophenol, and 2,6-dichloro-p-benzoquinon, et al. This work provides a facile method for the preparation of Co-based composite oxide catalysts, which represent promising candidates for typical chlorinated and oxygenated volatile organic compounds. [ABSTRACT FROM AUTHOR]

Clinical trials focusing on therapeutic candidates that modify β-amyloid (Aβ) have repeatedly failed to treat Alzheimer's disease (AD), suggesting that Aβ may not be the optimal target for treating AD. The evaluation of Aβ, tau, and neurodegenerative (A/T/N) biomarkers has been proposed for classifying AD. However, it remains unclear whether disturbances in each arm of the A/T/N framework contribute equally throughout the progression of AD. Here, using the random forest machine learning method to analyze participants in the Alzheimer's Disease Neuroimaging Initiative dataset, we show that A/T/N biomarkers show varying importance in predicting AD development, with elevated biomarkers of Aβ and tau better predicting early dementia status, and biomarkers of neurodegeneration, especially glucose hypometabolism, better predicting later dementia status. Our results suggest that AD treatments may also need to be disease stage-oriented with Aβ and tau as targets in early AD and glucose metabolism as a target in later AD. Here the authors analyze the Alzheimer's Disease Neuroimaging Initiative dataset using random forest machine learning methods and determine that Aβ and tau biomarkers are better predictors of early dementia status, while glucose hypometabolism is a better predictor of later dementia status. These results suggest the need for stage-oriented Alzheimer's disease treatments. [ABSTRACT FROM AUTHOR]

We develop a method to capture marine bacterial strains at high efficiency to replace the conventional two-step collecting method. Lab-made, Fe3O4 magnetic beads were used to firstly verify the feasibility of capture in artificial seawater, using Bacillus velezensis. Almost 100% of the bacteria could be captured and separated within 10 min. Then, the salinity of capture medium was proved to have the most marked effect on the capture process. After that, the broad application and high efficiency of capture were verified using four different bacterial strains from the Pacific Ocean. Subsequently, through adjusting the salinity, the capture efficiency for Pseudoalteromonas sp. and Halomonas meridiana was increased from 20 to ~ 80% in a seawater system, which was used to simulate the in-situ capture conditions. Finally, mixed strains in seawater were successfully captured, and their genomic DNAs were isolated and analyzed. Bare Fe3O4 magnetic beads were initially applied to capture marine microorganisms and this method is convenient and highly efficient and thus has great potential to replace the conventional two-step method. [ABSTRACT FROM AUTHOR]

In order to investigate the heavy metal pollution level and distribution characteristics in different particle sizes, and to evaluate the health risk, 42 street dust samples were collected in January 2015 from Huangshi, as an industrial city in Central China. The results analyzed by flame atomic absorption spectrometry (FAAS) showed that the average content of Cu, Pb, Zn, Cd, Mn, and Fe in the fine particle diameter (< 25 μm) was 1041.12, 361.64, 890.00, 14.43, 3178.52, and 61841.79 mg kg−1, respectively. Meanwhile, the average content of Cu, Pb, Zn, Cd, Mn, and Fe in the coarse particle diameter (25 < D < 75 μm) was 1628.54, 401.52, 593.16, 9.54, 5316.07, and 76765.37 mg kg−1, respectively. Compared with other cities, the heavy metal pollution of street dust in Huangshi was more serious. The results indicated that heavy metals were more easily enriched in fine grains street dust, except for Cu, Mn, and Fe. The heavy metal elements showed obvious spatial heterogeneity in different regions, and the interference from human sources was greater. Heavy metals in Huangshi street dust are generally at moderate or higher pollution levels (except Fe), of which Cu and Cd are the most seriously polluted. Multivariate statistical analysis shows that the heavy metals in fine-grained street dust mainly come from traffic/industrial mixed sources (74.5%) and industrial sources (25.5%); the heavy-grained street dust heavy metals mainly come from mixed traffic/industrial sources (55.1%) and soil source (44.9%). For non-carcinogenic heavy metals, mainly through the hand-mouth contact pathway into the human body, there are also no non-carcinogenic health risks in both hand-mouth ingestion and dermal contact. For carcinogenic heavy metals, Cd in street dust did not have carcinogenic risk. [ABSTRACT FROM AUTHOR]

The methylotrophic bacterium Methylorubrum extorquens AM1 holds a great potential of a microbial cell factory in producing high value chemicals with methanol as the sole carbon and energy source. However, many gene functions remain unknown, hampering further rewiring of metabolic networks. Clustered regularly interspaced short palindromic repeat interference (CRISPRi) has been demonstrated to be a robust tool for gene knockdown in diverse organisms. In this study, we developed an efficient CRISPRi system through optimizing the promoter strength of Streptococcus pyogenes–derived deactivated cas9 (dcas9). When the dcas9 and sgRNA were respectively controlled by medium PR/tetO and strong PmxaF-g promoters, dynamic repression efficacy of cell growth through disturbing a central metabolism gene glyA was achieved from 41.9 to 96.6% dependent on the sgRNA targeting sites. Furthermore, the optimized CRISPRi system was shown to effectively decrease the abundance of exogenous fluorescent protein gene mCherry over 50% and to reduce the expression of phytoene desaturase gene crtI by 97.7%. We then used CRISPRi technology combined with 26 sgRNAs pool to rapidly discover a new phytoene desaturase gene META1_3670 from 2470 recombinant mutants. The gene function was further verified through gene deletion and complementation as well as phylogenetic tree analysis. In addition, we applied CRISPRi to repress the transcriptional level of squalene-hopene cyclase gene shc involved in hopanoid biosynthesis by 64.9%, which resulted in enhancing 1.9-fold higher of carotenoid production without defective cell growth. Thus, the CRISPRi system developed here provides a useful tool in mining functional gene of M. extorquens as well as in biotechnology for producing high-valued chemicals from methanol. Key points: Developing an efficient CRISPRi to knockdown gene expression in C1-utilizing bacteria CRISPRi combined with sgRNAs pool to rapidly discover a new phytoene desaturase gene Improvement of carotenoid production by repressing a competitive pathway [ABSTRACT FROM AUTHOR]

To improve the transmission performance of XCTD channel, this paper proposes a method to measure directly and fit the channel transmission characteristics by using frequency sweeping method. Sinusoidal signals with a frequency range of 100 Hz to 10 kHz and an interval of 100 Hz are used to measure transmission characteristics of channels with lengths of 300 m, 800 m, 1300 m, and 1800 m. The correctness of the fitted channel characteristics by transmitting square wave, composite waves of different frequencies, and ASK modulation are verified. The results show that when the frequency of the signal is below 1500 Hz, the channel has very little effect on the signal. The signal compensated for amplitude and phase at the receiver is not as good as the uncompensated signal. Alternatively, when the signal frequency is above 1500 Hz, the channel distorts the signal. The quality of signal compensated for amplitude and phase at receiver is better than that of the uncompensated signal. Thus, we can select the appropriate frequency for XCTD system and the appropriate way to process the received signals. Signals below 1500 Hz can be directly used at the receiving end. Signals above 1500 Hz are used after amplitude and phase compensation at the receiving end. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: There is conflicting evidence on whether intermittent catheterization (IC) is less associated with urinary tract infection (UTI) and more likely to prevent urinary retention than continuous catheterization (CC). We aimed to compare the effect of IC with that of CC on the incidence of postpartum UTI, urinary retention and hemorrhage in laboring women with epidural analgesia. Methods: Electronic searches were performed in PubMed, EMBASE and Cochrane Library from their inception to October 2018. We selected RCTs comparing IC with CC in laboring women with epidural analgesia. A meta-analysis was performed using the RevMan software, and a random-effects model was used to pool the effect size. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence. Results: Six RCTs (N = 850) were included in this review. The meta-analyses indicated that there was no significant difference between the IC and CC group in the incidence of postpartum UTI (RR = 1.25, 95% CI: 0.91 to 1.71, P = 0.16), postpartum urinary retention (RR = 0.76, 95% CI: 0.21 to 2.77, P = 0.68) and postpartum hemorrhage (RR = 1.72, 95% CI: 0.60 to 4.95, P = 0.31). GRADE assessment results showed that the quality of evidence was low. Conclusions: Based on the available evidence, there is no measurable difference in rates of UTI between CC and IC, not that neither stragety decreases UTI, since the included trials do not address this. [ABSTRACT FROM AUTHOR]

Aims: Evidence indicates that curcumin seems to improve outcomes in non-alcoholic fatty liver disease (NAFLD). A meta-analysis was performed to evaluate the effects of curcumin inNAFLD. Methods: We searched PubMed, EMBASE, and the Cochrane Library from inception through March 2018 to identify randomized controlled trials (RCTs) evaluating the role of curcumin inNAFLD. The mean difference (MD) and 95% confidence interval (CI) were calculated. Results: Four RCTs with a total of 229 NAFLD patients were included. Curcumin was more likely to lower LDL-C, triglycerides, FBS, HOMA-IR, weight and AST levels compared with placebo, and the difference was statistically significant [MD = − 27.02, 95% CI (− 52.30, − 1.74); MD = − 33.20, 95% CI (− 42.30, − 24.09); MD = − 5.63, 95% CI (− 10.36, − 0.90); MD = − 0.53, 95% CI (− 1.00, − 0.05); MD = − 2.27, 95% CI (− 3.11, − 1.44); MD = − 7.43, 95% CI (− 11.31, − 3.54), respectively]. However, the beneficial effect of curcumin did not achieve statistical significance in lowering total cholesterol, HDL-C, HbA1c, ALT or insulin levels [MD = − 30.47,95% CI (− 60.89. − 0.06); MD = − 0.98, 95% CI (− 2.88, 0.92); MD = − 0.41, 95% CI (− 1.41, 0.59); MD = − 6.02, 95% CI (− 15.61, 3.57); MD = − 0.92, 95% CI (− 2.33, 0.49)]. Conclusions: Curcumin is effective in lowering LDL-C, triglycerides, FBS, HOMA-IR, weight, and AST levels in NAFLD patients, and it is well tolerated. Further RCTs are required to confirm our findings. [ABSTRACT FROM AUTHOR]

Crude violacein, consisting of violacein and deoxyviolacein, displays many attractive bio-activities in the field of drug therapy. To produce crude violacein from an industrially economic carbon source, we firstly introduced the violacein pathway into Escherichia coli B8/pTRPH1, which was previously engineered to accumulate tryptophan from glucose. A crude violacein production capacity of 0.25 g L−1 OD600−1 was obtained using glucose-containing medium. By further overexpressing each of the five genes involved in violacein synthesis pathway, VioE was found as the rate-limiting step for the violacein production. The optimal strain of B8/pTRPH1-pVio-VioE was then used for fed-batch fermentation in a 5-L bioreactor and a crude violacein titer of 4.45 g L−1, as well as a productivity of 98.7 mg L−1 h−1, was obtained. This engineered strain showed the highest violacein titer and productivity reported so far. Our optimal strain of E. coli B8/pTRPH1-pVio-VioE by overexpression of the rate-limiting VioE in violacein synthesis pathway was a potential violacein producer by directly using glucose for industrial application. [ABSTRACT FROM AUTHOR]

Terpenoids are a large family of natural compounds that are important for both biotechnological applications and basic microorganism physiology. Inspired by the current literature, we hypothesized that recently deciphered phosphatase promiscuity may be an unexplored factor that negatively affects terpenoid biosynthesis by redirecting carbon flux away from the pathway via unrecognized catalytic activities on the phosphorylated intermediates. We used lycopene as a proof-of-concept to test this hypothesis. Based on an extensive bioinformatics analysis, we selected 56 phosphatase-encoding genes in Escherichia coli and constructed a knockdown library for these genes in a lycopene overproducer via CRISPR interference (CRISPRi). We screened this phosphatase knockdown library and observed enrichment (28 of 56) for genes that impair lycopene biosynthesis. Further scaled-up cultivation, combinatorial knockdown, and knockout assays in strains that overproduce lycopene or another terpenoid (β-carotene) confirmed the proposed relationship between promiscuous phosphatases and impaired terpenoid biosynthesis. This study hence suggests the necessity of reconsidering the interactions of promiscuous phosphatases with ubiquitous phosphorylated components of metabolic networks with respect to engineering metabolism. [ABSTRACT FROM AUTHOR]

Ethylene oxide is a most versatile and critical raw chemical and intermediate. However, the strained ring of ethylene oxide is liable to be cleaved, potentially leading to industrial disasters at high temperatures, such as severe explosions, fires, and toxic releases. In this study, nonisothermal, adiabatic, and isothermal tests were performed to determine the inherent properties of aqueous ethylene oxide solution (AEOS) with regard to its safety. Differential scanning calorimetry and vent sizing package 2 were used to investigate its thermal decomposition and pseudo-adiabatic runaway reaction, respectively. Isothermally exothermic behavior was detected by using the thermal activity monitor IV. Kinetic equations were applied to calculate the apparent activation energy of AEOS (at conversion degrees of 10, 11, 12, 13,…, and 90%), with its value in the range 59.6-85.0 kJ mol−1. The Arrhenius method was also used to ascertain the frequency factor. As the conversion degree increased, the apparent activation energy and frequency factor gradually decreased. The flash point of AEOS was tested to determine its fire and explosion hazard potential. From the perspective of proactive loss prevention, these results are salient for the safer thermal handling of AEOS. [ABSTRACT FROM AUTHOR]

Methylobacterium extorquens AM1 is the model strain for methylotrophic bacteria that metabolize methanol as the sole carbon and energy source. Genetically modified M. extorquens AM1 is used as a methylotrophic cell factory (MeCF) for high value-added chemical production. We tested the Cre-loxP recombination system for its ability to mediate multicopy gene integration of the mvt3 operon (mvt3) in M. extorquens AM1. mvt3 controls the expression of the first three enzymes of the mevalonate synthesis pathway. We assayed for Cre-mediated multigene integration by screening for multicopy mutants via their survival in culture with a high kanamycin concentration (600 μg/mL). We identified mutant strains in which the mevalonate titer was increased by up to 1.9-fold compared with M2 (M. extorquens AM1ΔcelABCΔattTn7::mvt3::loxP) and confirmed mvt3 integration at 2-3 copies per genome. This result demonstrates the feasibility of multicopy integration in M. extorquens AM1 mediated by Cre-loxP recombination and its potential for improving the output of M. extorquens AM1 metabolic pathways, e.g., optimization of terpenoid synthesis. [ABSTRACT FROM AUTHOR]

We analyze the impact of open-access (OA) articles published by China and the USA by using Web of Science (WoS) data covering a period of 5 years (2011-2015), five indexes (citation and four altmetric indexes), five disciplines, and three types of articles. With regard to article type, Type I papers are those wherein the authors are all from China or the USA. Type II are those in which the first author is from China or the USA. Type III includes those in which the first author is not from China or the USA. We found that the proportion of OA papers in WoS has been growing in recent years. In terms of citations and altmetric indexes, the mean value of the USA is larger than that of China in general; Type II articles possess the highest value among all papers in the USA, whereas Type III has the highest value in China. Compared with the scenario in citations, social sciences and humanities possess larger altmetric values in China and the USA. The correlation among indicators is similar for the OA papers from China and the USA. Generally, citations cannot effectively represent the altmetric indexes. The gap between China and the USA is the largest in the altmetric attention score and Type I, and the smallest in citations and Type III. Measuring the international impact of OA papers using only citations underestimates the gap between China and the USA. [ABSTRACT FROM AUTHOR]

Aim: To provide a systematic review of the existing theory, framework, systems and instruments for tracing and evaluating quality in rural health services.Subjects and methods: We searched six electronic databases up to March 2016. Observational studies of quality assessment of rural health services using theoretical models were included. Ekman’s scale was used to evaluate the quality of the included studies.Results: A total of 18 studies, published between 2001 and 2015, met the inclusion criteria. The corresponding authors for most of them (7, 44%) are from Chinese institutions and three (3, 17%) from Australian institutions. Five studies (28%) focused on township hospitals. Primary health care quality was reported in five studies (28%), followed by clinical service in four (22%). More than half of the studies (61%) were considered of high quality, and the remainder was of moderate quality. These studies applied 16 theoretical systems, including the model/pattern (4, 25%), method/tool (7, 44%) and framework of the theory (5, 31%). Most of the theoretical models (14, 88%) obtained positive observations. In addition, the conceptual model (6, 36%) and TOPSIS method (2, 13%) were more frequently reported.Conclusion: Although most of the current studies were considered to have high-quality and positive results, there were limitations in the number of publications and research on theoretical systems. The lacks of unified standards and comprehensive evaluation are important issues that need to be pointed out and resolved. [ABSTRACT FROM AUTHOR]

In methane-rich environments, methane-oxidizing bacteria usually occur predominantly among consortia including other types of microorganisms. In this study, artificial coal bed gas and methane gas were used to enrich mixed methanotrophic cultures from the soil of a coal mine in China, respectively. The changes in microbial community structure and function during the enrichment were examined. The microbial diversity was reduced as the enrichment proceeded, while the capacity for methane oxidation was significantly enhanced by the increased abundance of methanotrophs. The proportion of type II methanotrophs increased greatly from 7.84 % in the sampled soil to about 50 % in the enrichment cultures, due to the increase of methane concentration. After the microbial community of the cultures got stable, Methylomonas and Methylocystis became the dominant type I and type II methanotrophs, while Methylophilus was the prevailing methylotroph. The sequences affiliated with pigment-producing strains, Methylomonas rubra, Hydrogenophaga sp. AH-24, and Flavobacterium cucumis, could explain the orange appearance of the cultures. Comparing the two cultures, the multi-carbon sources in the artificial coal bed gas caused more variety of non-methanotrophic bacteria, but did not help to maintain the diversity or to increase the quantity and activity of methanotrophs. The results could help to understand the succession and interaction of microbial community in a methane-driven ecosystem. [ABSTRACT FROM AUTHOR]

Mining activities are among the major culprits of the wide occurrences of soil and water pollution by PAHs in coal district, which have resulted in ecological fragilities and health risk for local residents. Sixteen PAHs in multimedia environment from the Heshan coal district of Guangxi, South China, were measured, aiming to investigate the contamination level, distribution and possible sources and to estimate the potential health risks of PAHs. The average concentrations of 16 PAHs in the coal, coal gangue, soil, surface water and groundwater were 5114.56, 4551.10, 1280.12 ng g, 426.98 and 381.20 ng L, respectively. Additionally, higher soil and water PAH concentrations were detected in the vicinities of coal or coal gangue dump. Composition analysis, isomeric ratio, Pearson correlation analysis and principal component analysis were performed to diagnose the potential sources of PAHs in different environmental matrices, suggesting the dominant inputs of PAHs from coal/coal combustion and coal gangue in the soil and water. Soil and water guidelines and the incremental lifetime risk (ICLR) were used to assess the health risk, showing that soil and water were heavily contaminated by PAHs, and mean ICLR and mean ICLR were both significantly higher than the acceptable levels (1 × 10), posing high potential carcinogenic risk to residents, especially coal workers. This study highlights the environmental pollution problems and public health concerns of coal mining, particularly the potential occupational health hazards of coal miners exposed in Heshan. [ABSTRACT FROM AUTHOR]

Methylotrophic biosynthesis using methanol as a feedstock is a promising and attractive method to solve the over-dependence of the bioindustry on sugar feedstocks derived from grains that are used for food. In this study, we introduced and engineered the mevalonate pathway into Methylobacterium extorquens AM1 to achieve high mevalonate production from methanol, which could be a platform for terpenoid synthesis. We first constructed a natural operon (MVE) harboring the mvaS and mvaE genes from Enterococcus faecalis as well as an artificial operon (MVH) harboring the hmgcs1 gene from Blattella germanica and the tchmgr gene from Trypanosoma cruzi that encoded enzymes with the highest reported activities. We achieved mevalonate titers of 56 and 66 mg/L, respectively, in flask cultivation. Introduction of the phaA gene from Ralstonia eutropha into the operon MVH increased the mevalonate titer to 180 mg/L, 3.2-fold higher than that of the natural operon MVE. Further modification of the expression level of the phaA gene by regulating the strength of the ribosomal binding site resulted in an additional 20 % increase in mevalonate production to 215 mg/L. A fed-batch fermentation of the best-engineered strain yielded a mevalonate titer of 2.22 g/L, which was equivalent to an overall yield and productivity of 28.4 mg mevalonate/g methanol and 7.16 mg/L/h, respectively. The production of mevalonate from methanol, which is the initial, but critical step linking methanol with valuable terpenoids via methylotrophic biosynthesis, represents a proof of concept for pathway engineering in M. extorquens AM1. [ABSTRACT FROM AUTHOR]

Objective: To characterize a novel xanthine dehydrogenase (XDH) from Acinetobacter baumannii by recombinant expression in Escherichia coli and to assess its potential for industrial applications. Results: The XDH gene cluster was cloned from A. baumannii CICC 10254, expressed heterologously in E. coli and purified to homogeneity. The purified recombinant XDH consisted of two subunits with the respective molecular weights of 87 kDa and 56 kDa according to SDS-PAGE. XDH catalysis was optimum at pH 8.5 and 40-45 °C, was stable under alkaline conditions (pH 7-11) and the half-inactivation temperature was 60 °C. The K, turnover number and catalytic efficiency for xanthine were 25 μM, 69 s and 2.7 μM s, respectively, which is an improvement over XDHs characterized previously. A. baumannii XDH is less than 50 % identical to previously identified XDH orthologs from other species, and is the first from the Acinetobacter genus to be characterized. Conclusion: The novel A. baumannii enzyme was found to be among the most active, thermostable and alkaline-tolerant XDH enzymes reported to date and has potential for use in industrial applications. [ABSTRACT FROM AUTHOR]

Flexibility or rigidity of the linker between two fused proteins is an important parameter that affects the function of fusion proteins. In this study, we constructed a linker library with five elementary units based on the combination of the flexible (GGGGS) and the rigid (EAAAK) units. Molecular dynamics (MD) simulation showed that more rigid units in the linkers lead to more helical conformation and hydrogen bonds, and less distance fluctuation between the N- and C-termini of the linker. The diversity of linker flexibility of the linker library was then studied by fluorescence resonance energy transfer (FRET) of cyan fluorescent protein (CFP)-yellow fluorescent protein (YFP) fusion proteins, which showed that there is a wide range of distribution of the FRET efficiency. Dissipative particle dynamics (DPD) simulation of CFP-YFP with different linkers also gave identical results with that of FRET efficiency analysis, and we further found that the combination manner of the linker peptide had a remarkable effect on the orientation of CFP and YFP domains. Our studies demonstrated that the construction of the linker library with the widely controllable flexibility could provide appropriate linkers with the desirable characteristics to engineer the fusion proteins with the expected functions. [ABSTRACT FROM AUTHOR]

DNA damage is the dominant source of mutation, which is the driving force of evolution. Therefore, it is important to quantitatively analyze the DNA damage caused by different mutagenesis methods, the subsequent mutation rates, and their relationship. Atmospheric and room temperature plasma (ARTP) mutagenesis has been used for the mutation breeding of more than 40 microorganisms. However, ARTP mutagenesis has not been quantitatively compared with conventional mutation methods. In this study, the umu test using a flow-cytometric analysis was developed to quantify the DNA damage in individual viable cells using Salmonella typhimurium NM2009 as the model strain and to determine the mutation rate. The newly developed method was used to evaluate four different mutagenesis systems: a new ARTP tool, ultraviolet radiation, 4-nitroquinoline-1-oxide (4-NQO), and N-methyl- N'-nitro- N-nitrosoguanidine (MNNG) mutagenesis. The mutation rate was proportional to the corresponding SOS response induced by DNA damage. ARTP caused greater DNA damage to individual living cells than the other conventional mutagenesis methods, and the mutation rate was also higher. By quantitatively comparing the DNA damage and consequent mutation rate after different types of mutagenesis, we have shown that ARTP is a potentially powerful mutagenesis tool with which to improve the characteristics of microbial cell factories. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection varies in the outcomes depending on both viral and host factors. This study aims to investigate the associations of three single nucleotide polymorphisms (SNPs) of Toll-like receptor 7 (TLR7), rs179016, rs5743733, and rs1634323, with susceptibility to HCV infection and clearance. The three SNPs were genotyped in a high-risk Chinese population, including 444 HCV spontaneous clearance cases, 732 persistent infection cases, and 1107 healthy controls. The G allele of rs1634323 was related to the protection from persistent infection among females (dominant model: odds ratio (OR) = 0.558, 95 % confidence interval (CI) = 0.348-0.894, P = 0.015). This protective effect was more evident in blood donation and HCV non-1 genotype-infected subgroups (all P < 0.05). The carriage of rs179016 C allele was more prone to develop persistent infection (OR = 1.444, 95 % CI = 1.096-1.903, P = 0.009) in males, and the risk effect remained significant among older (>50 years), hemodialysis (HD), and HCV-1 and HCV non-1 genotypes-infected subjects (all P < 0.05). Haplotype analyses showed that CCA haplotype among females was correlated with the elevated risk of HCV susceptibility while the carriage of GGA was more prone to be infected with HCV and CCA was more likely to develop persistent infection (all P < 0.05) among males. Our results first demonstrated that the carriage of rs179016 C allele had a negative effect on spontaneous clearance of HCV among males while rs1634323 G allele conferred a protective effect against persistent infection among female subjects. [ABSTRACT FROM AUTHOR]