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BACKGROUND: Numerous studies have identified a relationship between hemoglobin (Hb) levels and mortality in patients with chronic kidney disease (CKD), which have raised concerns about the optimal Hb targets in correction of anemia. Our study is designed to investigate the potential effects of targeted Hb levels, aiming to give some evidence for therapy of renal anemia. METHODOLOGY/PRINCIPAL FINDINGS: A comprehensive search of Medline, Embase and the Cochrane Database of Systematic Reviews was performed in December 2011 and updated in February 2012 for any new trials. Randomized trials designed to evaluate effects of high (generally the Hb about 13.0 g/dL) and low Hb (generally the Hb about 10.0 g/dL) targets on clinical outcomes in CKD patients with anemia were collected. All statistical analysis was calculated using the RevMan software available free from the Cochrane Collaboration. 24 trials involving 10361 patients were identified. Our findings demonstrated a statistically significant increased risk of mortality in the high Hb levels (RR 1.18; 95% CI 1.02 to 1.37) while the high and low Hb groups were both treated with ESAs. Overall, compared with low Hb levels, high Hb levels are associated with increased risk of hypertension (RR 1.40; 95% CI 1.11 to 1.75), stroke (RR 1.73; 95% CI 1.31 to 2.29), and hospitalizations (RR 1.07; 95% CI 1.01 to 1.14). However, there are no significant differences in the risk of non-fatal myocardial infarction (RR 1. 13; 95% CI 0.79 to 1.61) and renal replacement therapy (RR 1. 00; 95% CI 0.85 to 1.18). CONCLUSIONS/SIGNIFICANCES: Targeting low Hb levels are beneficial to CKD patients especially in the predialysis population. The optimal Hb targets to aim for in CKD patients and at what Hb level the risks of adverse events begin to increase remain elusive. Future studies are still needed to elucidate these questions.

The new development pattern has identified two key avenues for the sustained advancement of high-quality agricultural and rural development: digitalisation and low-carbon development. The measurement of the digital economy and the agricultural carbon emission performance, and their spatial and temporal heterogeneity, is a crucial step in promoting the spatial coordination and sustainable development of digitalisation and low-carbon agriculture. This paper employs the entropy value method, SBM model, and coupling coordination degree model to investigate the coupling coordination measurement and spatial-temporal heterogeneity of the performance of the digital economy and agricultural carbon emissions. The data used are provincial panel data from 2013 to 2021. The simulation results demonstrate that, between 2013 and 2021, the digital economy of all provinces exhibited varying degrees of growth, yet the development of the digital economy between provinces exhibited a more pronounced tendency to diverge. Concurrently, the agricultural carbon emission efficiency in China exhibited a fluctuating upward trend. The development of the digital economy and the efficiency of agricultural carbon emission were found to be highly coupled. Their coupling and coordination relationship showed a downward trend followed by an upward trend. In general, it is suggested that we should increase investment in digital economy infrastructure and technology, promote digital agricultural applications, strengthen policy guidance and financial support, establish a coupling coordination mechanism and strengthen farmers' digital literacy and environmental awareness., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study constructed a multidimensional indicator system to evaluate spatio-temporal heterogeneity of China's import and export trade of 31 provinces from 2000 to 2022. This study describes the distribution of China's import and export trade by using location Gini coefficient and exploratory spatial analysis. Additionally, Multiple linear regression was used to ascertain the extent of contribution by various factors on the spatio-temporal heterogeneity of import and export trade. The simulation results show that inter-provincial import and export trade displayed distinct spatio-temporal differentiation characteristics with a prominent east-to-west disparity from 2000 to 2022. The trade links between various regions of the country have gradually strengthened, with a corresponding high correlation to the level of economic development. GDP, financial expenditure, freight transportation volume, technology market turnover, foreign investment, and disposable income of all residents, significantly influence the per capita export and import volume. In general, it is suggested that China and developing countries should take effective measures to promote balanced trade development, strengthen regional cooperation and coordination, and promote green trade and sustainable development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The construction of expressways in China has produced diverse habitats along slopes characterized by steep gradients, uneven water distribution, poor soil conditions, and no routine maintenance. Manually planting beneficial species is an essential method of effectively improving slope soils to prevent soil erosion. However, few studies have evaluated the reclamation effects and plant community composition and structure used to restore slopes along expressways. This study focused on the Zhengzhou-Xinxiang section of the Beijing-Hong Kong-Macao Expressway. A total of 10 representative plant communities were evaluated using the analytic hierarchy process (AHP)-fuzzy integrated evaluation method. The sites were divided into four layers, namely, plant communities, soil nutrients, soil physical properties, and other ecological factors, and 14 indicators were assessed. The evaluation results showed that four of these plant communities (PCs) were excellent, three PCs were good, one PC was normal, two PCs were poor. The four excellent PCs had high Shannon-Wiener index, pielou index, richness index or community productivity. It is worth noting that most excellent plant community structures were tree + shrub + herb. Based on these results, we recommend that fill slopes should be restored using a combination of trees, herbs, and shrubs; also, the vegetation should include native plants, such as B. papyrifera, U. pumila, A. fruticosa, and Cynodon dactylon (L.). This study could provide ideas for plant community composition and structure of new highway slopes in similar climate environment, and provide theoretical support for plant community composition and structure and soil improvement for the existing slope., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Iron-Heart Cunninghamia lanceolata, a wild relative of Chinese fir with valuable genetic and breeding traits, has been limited in genetic studies due to a lack of genomic resources and markers. In this study, we conducted transcriptome sequencing of Iron-Heart C. lanceolata leaves using Illumina NovaSeq 6000 and performed assembly and analysis. We obtained 45,326,576 clean reads and 115,501 unigenes. Comparative analysis in five functional databases resulted in successful annotation of 26,278 unigenes, with 6,693 unigenes annotated in all databases (5.79% of the total). UniProt and Pfam databases provided annotations for 22,673 and 18,315 unigenes, respectively. Gene Ontology analysis categorized 23,962 unigenes into three categories. KEGG database alignment annotated 10,195 unigenes, classifying them into five categories: metabolism, genetic information, biological systems, cellular processes, and environmental information processing. From the unigenes, we identified 5,645 SSRs, with dinucleotides repeats being the most common (41.47%). We observed variations in repeat numbers and base compositions, with the majority of markers ranging from 12 to 29 bp in length. We randomly selected 200 primer pairs and successfully amplified 15 pairs of polymorphic SSR primers, which effectively distinguished Chinese fir plants of different origins. This study provides insights into the genetic characteristics of Iron-Heart C. lanceolata and offers a foundation for future molecular marker development, breeding programs, genetic diversity analysis, and conservation strategies., Competing Interests: NO authors have competing interests., (Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Accurate evaluation of morphological changes in articular cartilage are necessary for early detection of osteoarthritis (OA). 3T magnetic resonance imaging (MRI) has highly sensitive contrast resolution and is widely used clinically to detect OA. However, synchrotron radiation phase-contrast imaging computed tomography (SR-PCI) can also provide contrast to tissue interfaces that do not have sufficient absorption differences, with the added benefit of very high spatial resolution. Here, MRI was compared with SR-PCI for quantitative evaluation of human articular cartilage. Medial tibial condyles were harvested from non-OA donors and from OA patients receiving knee replacement surgery. Both imaging methods revealed that average cartilage thickness and cartilage volume were significantly reduced in the OA group, compared to the non-OA group. When comparing modalities, the superior resolution of SR-PCI enabled more precise mapping of the cartilage surface relative to MRI. As a result, MRI showed significantly higher average cartilage thickness and cartilage volume, compared to SR-PCI. These data highlight the potential for high-resolution imaging of articular cartilage using SR-PCI as a solution for early OA diagnosis. Recognizing current limitations of using a synchrotron for clinical imaging, we discuss its nascent utility for preclinical models, particularly longitudinal studies of live animal models of OA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bairagi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To carry out differentiated ecological restoration activities and formulate appropriate environmental conservation strategies for karst regions, it is essential to investigate the impact of ecological restoration and forest management strategy differences on soil properties. The karst region in Xiangxi, Hunan province, China was selected as the study site. Here, we determined soil physical and chemical differences in soil profiles of karst areas with ecological restoration activities. The results showed that (1) the soil properties showed a significant difference between the restoration vegetation and uncultivated land, especially in soil physical properties. The soil moisture conversion coefficient (83.0%) and soil bulk density (1.37g/cm3) of Liriodendron chinense (Hemsl.) Sarg reached the highest value among 12 vegetations. 2) The topsoil was more sensitive to ecological restoration. Soil physical properties in the topsoil samples from the forest management areas were significantly higher than uncultivated lands (P < 0.05). (3) Redundancy analysis showed that the soil chemical content differed significantly among the types of forest vegetation restoration and different soil layers. Among the nutrients analysis, Mg, Zn and K were the main factors affecting soil properties in the rocky desertification areas. Therefore, our results recommend planting the broadleaved deciduous forest as the preferred forest among three different forest types to enhance soil fertility and water conservation functions, especially in subtropical karst areas ecosystems, which provided for making scientific forest restoration management in the karst region., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xiao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In China, industrial pollution has become an urgent problem for policy makers and enterprise managers. To better support industrial development, we need to determine the effectiveness of policies through efficiency evaluation. China's provincial industrial system consists of two stages: production and emission reduction. The emission reduction stage is composed of three parallel sub stages: solid waste treatment, waste gas treatment and wastewater treatment. In this process, the treatment capacity of industrial wastewater treatment facilities can be used as carry forward variable, which is not only the desirable output of the previous emission reduction stage, but also the input of the current emission reduction stage. Therefore, this paper proposes a dynamic hybrid two-stage data envelopment analysis (DEA) model for eco-efficiency evaluation of industrial systems, and applies it to a case study of Chinese regional industry. Applying the data collected from 2011 to 2015 to the model, the following conclusions can be drawn: (1) During the whole survey period, the average eco-efficiency was 0.9027. The overall eco-inefficiency of China's provincial industrial system during the study period is mainly due to low efficiency of solid waste treatment and waste gas treatment. (2) The average eco-efficiency of provincial industrial system increased steadily from 2011 (0.6448) to 2014 (0.6777), but decreased slightly in 2015 (0.5908). (3) The carry forward treatment capacity of industrial wastewater treatment facilities has a remarkable impact on provincial industrial system efficiency scores, especially at the wastewater treatment stage (0.6002 vs 0.3691). (4) Provincial industrial system exists distinct geographical characteristics of low efficiency. This study has important guiding significance for policy makers and enterprise managers who are concerned about industrial pollution control., Competing Interests: The authors have declared that no competing interests exist.

As haze pollution intensifies, its impact on tourism is becoming increasingly obvious. However, limited studies have analyzed the impacts of haze pollution on tourism. To explore the contribution rate and impact of PM2.5 pollution on tourism flows, panel data on 341 prefecture-level cities in China from 2001 to 2015 were used. The results illustrated that the changes in PM2.5 pollution and domestic tourism flows showed a similar partial-most anti-phase main spatial pattern in space, as well as other spatial patterns of PM2.5. From a regional perspective, the contribution rate of PM2.5 to domestic tourism flows was less than that of traditional factors, such as GDP, GDP&#95;500, and 45A, but larger than that of the Airport factor. The contribution rate of the interaction between PM2.5 and 45A on domestic tourism flows was the largest. From a local perspective, PM2.5 pollution had a negative impact on domestic tourism flows in northern China, while it had a positive impact in other regions. The classic environmental Kuznets curve (EKC) hypothesis showed applicability to the Chinese tourism industry, and the is of great significance for comprehensively understanding the impact of PM2.5 pollution on tourism flows and for promoting the sustainable development of domestic tourism., Competing Interests: The authors have declared that no competing interests exist.

South Asia primarily consists of developing economies with diverse financial systems. The commercial banking industry plays a crucial role in each country's financial development in the region. This research aims to evaluate commercial banking industries' efficiency and productivity growth in the South Asian (SA) region over 6 years (2013-2018). In addition, the technology gap among the banking industries of all countries is also explored. Data envelopment analysis (DEA) Meta-frontier is employed to measure the technical efficiency (TE) and technology gap ratio (TGR) among the countries. Further Malmquist productivity index (MPI) is used for productivity change estimation. Results indicate that, on average, 147 commercial banks (CBs) have a technical efficiency score of 0.6208, while CBs in Nepal are the most efficient in the region with an average score of 0.7153. The Meta frontier analysis also confirms the presence of different production technologies in CBs. Nepal's CBs group frontier is closer to meta-frontier (technology gap ratio, TGR = 0.9361) While, Bangladesh, Pakistan, India, and Sri Lanka rank second, third, fourth, and fifth, respectively. The results of productivity contend that the total factor productivity change of all 147 CBs decreases by 0.8 percent on average over the study period. CBs have enhanced their productivity growth in Sri Lanka, Nepal, and Pakistan, but declining trends have been witnessed in Indian and Bangladesh's commercial banking industries., Competing Interests: The authors have declared that no competing interests exist.

In the 12th Five-Year Plan period, Sichuan province has selected strategic emerging industries such as new-generation information technology, new energy, high-end equipment manufacturing, new materials, biology, energy conservation and environmental protection. However, its strategic emerging industries are still in the stage of cultivation and development, and there are some problems such as low industrial agglomeration and obvious industrial restructuring. In essence, this is because the focus of the development of strategic emerging industries is not clear enough, and the location advantages are not fully utilized to select the most suitable strategic emerging industries for the development of the region. This paper constructs a regional strategic emerging industries selection decision model, applies ARCGIS to study the spatial distribution of strategic emerging industries in Sichuan province, and uses fuzzy comprehensive evaluation method (FCEM) and analytic hierarchy process (AHP) to solve the priority of developing strategic emerging industries. Conclusions: Firstly, Sichuan province should give priority to the development of new generation information technology industry and new energy vehicle industry, then high-end equipment manufacturing industry, energy-saving and environmental protection industry and new energy industry, and finally biological industry and new material industry. The larger the coefficient of influence is, the higher the comprehensive score is, while the larger the coefficient of sensitivity is, the lower the comprehensive score is. Secondly, the number of enterprises in the new-generation information technology industry and the new energy vehicle industry is still not dominant in Sichuan province. Finally, the study found that the current development of strategic emerging industries in Sichuan province is extremely unbalanced in various regions, and the phenomenon of competition and reconstruction is obvious., Competing Interests: The authors have declared that no competing interests exist.

In recent years, text sentiment analysis has attracted wide attention, and promoted the rise and development of stance detection research. The purpose of stance detection is to determine the author's stance (favor or against) towards a specific target or proposition in the text. Pre-trained language models like BERT have been proven to perform well in this task. However, in many reality scenes, they are usually very expensive in computation, because such heavy models are difficult to implement with limited resources. To improve the efficiency while ensuring the performance, we propose a knowledge distillation model BERTtoCNN, which combines the classic distillation loss and similarity-preserving loss in a joint knowledge distillation framework. On the one hand, BERTtoCNN provides an efficient distillation process to train a novel 'student' CNN structure from a much larger 'teacher' language model BERT. On the other hand, based on the similarity-preserving loss function, BERTtoCNN guides the training of a student network, so that input pairs with similar (dissimilar) activation in the teacher network have similar (dissimilar) activation in the student network. We conduct experiments and test the proposed model on the open Chinese and English stance detection datasets. The experimental results show that our model outperforms the competitive baseline methods obviously., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Spinal cord injury (SCI) is associated with severe autonomic dysfunction. Patients with SCI often suffer from a lack of central nervous system control over the gastrointestinal system. Therefore, we hypothesized that patients with SCI would cause intestinal flora imbalance. We investigated alterations in the fecal microbiome in a group of patients with SCI., Methods: Microbial communities in the feces of 23 patients and 23 healthy controls were investigated using high-throughput Illumina Miseq sequencing targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene. The relative abundances between the fecal microbiota at the genus level in patients with SCI and healthy individuals were determined using cluster analysis., Results: The structure and quantity of fecal microbiota differed significantly between patients with SCI and healthy controls, but the richness and diversity were not significantly different. A two-dimensional heatmap showed that the relative abundances of forty-five operational taxonomic units (OTUs) were significantly enriched either in SCI or healthy samples. Among these, 18 OTUs were more abundant in healthy controls than in patients with SCI, and 27 OTUs were more abundant in the SCI group than in healthy controls., Conclusion: Our study showed that patients with SCI exhibited microbiome dysbiosis., Competing Interests: The authors have declared that no competing interests exist.

The effect of microchip pulsed electric field (MPEF) treatment on lethal and sublethal injury of Pichia rhodanensis (P. rhodanensis) were employed under 100-500 V for 20-100 pulses and the underlying mechanism of MPEF treatment was investigated as well. A 6.48 log10 reduction of P. rhodanensis was achieved at 500V for 80 pulse. The fluorescent staining with Propidium Iodide (PI) verified that the rate of sublethal injury cells maximum up to 27.2% under 200 V. MPEF can cause the damage of cell morphology and ultrastructure, meanwhile causing a decrease in cellular enzymes, antioxidant enzyme activity and cell membrane fluidity. The leakage of intracellular compounds (protein, nucleic acid, K+, Mg2+) and Ca2+-ATPase gradually increased as the growth of voltage, especially the proportion of protein in the supernatants increased from 2.0% to 26.4%. Flow cytometry analysis showed that MPEF has significant effect on membrane potential, but no obvious influence on non-specific esterase. MPEF can cause the changing of the secondary structure of protein, at the same time, double helix structure of DNA became loose and unwinding. These results provide a theoretical guidance for the widespread using of MPEF technology in the application of a non-thermal processing technique for food., Competing Interests: The authors have declared that no competing interests exist.

The accurate identification and quality evaluation of herbal medical plants is highly necessary to ensure their safety and efficacy. In present study, a new strategy combining DNA barcoding techniques with thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) was proposed to facilitate the identification and quality control of M. tenacissima. In present work, the internal transcribed spacer 2 (ITS2) barcode was successfully used to identify 58 M. tenacissima samples and its adulterants. TLC successfully identified the other three M. tenacissima samples that failed to produce ITS2 regions. An adulterant was found in all the 62 samples. Moreover, the content of active medicinal ingredients is important for herbal plants quality. The content of tenacissoside H (TS-H) of M. tenacissima samples was determined by HPLC to range from 0.39% to 1.09%, which meets the criterion of the Chinese Pharmacopoeia. Thus, DNA barcoding coupled with TLC and HPLC is very promising to identify and evaluate the quality of M. tenacissima in the medicine market.

GNB2L1 and its O-GlcNAcylation has been reported to play roles in gastric cancer metastasis. However, the roles of GNB2L1 in chemoresistance of gastric cancer has never been determined. In the present study, we found that GNB2L1 was downregulated in chemoresistant patients of gastric cancer, and observed the decrease of GNB2L1 in protein levels instead of mRNA levels in different chemoresistant gastric cancer cell lines. Further we proved that this downregulation of GNB2L1 was resulted from its elevated O-GlcNAcylation catalyzed by OGT in both cell lines and patients. Next, we investigate the function of GNB2L1 and its O-GlcNAcylation on gastric cancer metastasis during chemoresistance, and confirmed Ser124 as the major O-GlcNAcylation site on GNB2L1 that regulated its function on metastasis. Furthermore, our data demonstrated that GNB2L1 modulated EMT via regulating the translation of EMT-related proteins in the process of chemoresistance. In summary, this study indicated that GNB2L1 and its O-GlcNAcylation regulated metastasis via modulating the translation of EMT-related proteins in the chemoresistance of gastric cancer.

Although adjuvants are a common component of many vaccines, there are few adjuvants licensed for use in humans due to concerns about their toxic effects. There is a need to develop new and safe adjuvants, because some existing vaccines have low immunogenicity among certain patient groups. In this study, SBP, a hepatitis B surface antigen binding protein that was discovered through screening a human liver cDNA expression library, was introduced into hepatitis B vaccine. A good laboratory practice, non-clinical safety evaluation was performed to identify the side effects of both SBP and SBP-adjuvanted hepatitis B vaccine. The results indicate that SBP could enhance the HBsAg-specific immune response, thus increasing the protection provided by the hepatitis B vaccine. The safety data obtained here warrant further investigation of SBP as a vaccine adjuvant., Competing Interests: The authors have declared that no competing interests exist.

Background: With lipid level being a major contributing factor for cardiovascular health, the high cardiovascular mortality among dialysis patients has raised substantial concerns in regard to the optimal lipid level in these patient population., Objective: To explore the optimal lipid level for the survival of dialysis patients., Methods: The lipid profile was measured for each patient. All participants were followed throughout the course of the study. Cox proportional hazards analysis was performed to analyze the prognostic value of lipid level on the survival of these patients., Results: In our study that included 311 stable maintenance dialysis patients, 54.98% of the participants had LDL-C level ≥100 mg/dl and 82.91% of the patients with triglycerides ≥200 mg/dl had non-HDL level ≥130 mg/dl. During the follow-up period of 48.0 (18.0, 55.5) months, 149 (47.91%) participants died. Among those who died, 59 patients died of cardiovascular disease (CVD) and 33 patients died of ischemic CVD (12.0, 4.7, and 2.7 events per 100 patient-years, respectively). Patients with LDL-C 100-130 mg/dl or non-HDL 130-160 mg/dl had a lower all-cause mortality rate than those who did not meet these criteria. After adjusting for the traditional and ESRD-related risk factors, non-HDL was found to be the independent risk factor for the all-cause mortality. Compared to those patients with non-HDL 130-160 mg/dl, patients with non-HDL <100 mg/dl, 100-130 mg/dl, 160-190 mg/dl, or ≥190 mg/dl all had higher all-cause mortality: HR (95% CI) 3.207 (1.801, 5.713), 2.493 (1.485, 4.184), 2.476 (1.423, 4.307), and 1.917 (1.099, 3.345), respectively. There were no differences in nutrition, comorbidity, and inflammation indices among the patients with different non-HDL groups. However, patients with non-HDL of 130-160 mg/dl had the lowest corrected calcium and calcium phosphate product values as compared with other non-HDL groups., Conclusion: Our study demonstrated that non-HDL 130-160 mg/dl might be the most appropriate lipid level in our dialysis patients. Our follow-up data also showed that patients with higher lipid level had poorer prognosis, just as in the general population., Competing Interests: The authors have declared that no competing interests exist.

Background: Hyperthyroidism affects about 0.2%-2.7% of all pregnancies, and is commonly managed with antithyroid drugs (ATDs). However, previous studies about the effects of ATDs on congenital anomalies are controversial. Therefore, the present meta-analysis was performed to explore the risk of congenital anomalies in children exposed to ATDs in-utero., Methods: Embase, Pubmed, Web of Knowledge, and BIOSIS Citation Index were searched to find out studies about congenital anomalies in children exposed to ATDs in-utero reported up to May 2014. The references cited by the retrieved articles were also searched. The relative risks (RRs) and confidence intervals (CIs) for the individual studies were pooled by fixed effects models, and heterogeneity was analyzed by chi-square and I2 tests., Results: Eight studies met the inclusion criteria. Exposure to propylthiouracil (PTU), methimazole/carbimazole (MMI/CMZ), and PTU & MMI/CMZ was investigated in 7, 7 and 2 studies, respectively. The pooled RR was 1.20 (95%CI: 1.02-1.42), 1.64 (95%CI: 1.39-1.92), and 1.83 (95%CI: 1.30-2.56) for congenital anomalies after exposure to PTU, MMI/CMZ, and PTU & MMI/CMZ, respectively., Conclusions: The meta-analysis suggests that exposure to ATDs in-utero increases the risk of congenital anomalies. The use of ATDs in pregnancy should be limited when possible. Further research is needed to delineate the exact teratogenic risk for particular congenital anomaly.

Background: Reduced neutrophil apoptosis plays an important role in the pathogenesis of acute exacerbation chronic obstructive pulmonary disease (AECOPD). The p38 mitogen-activated protein kinase (MAPK) signaling pathway is involved in neutrophil apoptosis. 1α,25-Dihydroxyvitamin D3 (1α,25VitD3) can induce tumor cell apoptosis. The aim of this study was to assess the effects of 1α,25VitD3 on peripheral blood neutrophil apoptosis in AECOPD and examine the role of the p38 MAPK signaling pathway., Methods: The study enrolled 36 AECOPD patients and 36 healthy volunteers. Venous blood samples were obtained from both groups. Serum 25-hydroxyvitamin D (25-(OH) D) levels in peripheral venous blood were assayed using liquid chromatography-tandem mass spectrometry (LC-MS/MS); the neutrophils were separated and cultured with SB203580 (a p38 inhibitor) and 1α,25VitD3. Neutrophil apoptosis was measured using flow cytometry, and phospho-p38 MAPK protein expression was detected by Western blot. Statistical analysis was performed using analysis of variance. Student's t-test and Pearson's correlation coefficient were used for the between-group differences and correlation analysis, respectively., Results: The 25-(OH) D levels were lower in AECOPD patients than in healthy controls, and the peripheral blood neutrophil apoptosis results were similar. 1α,25VitD3 increased the apoptosis rate and the level of phospho-p38 MAPK in peripheral blood neutrophils of AECOPD patients. SB203580 partly inhibited 1α,25VitD3-induced peripheral blood neutrophil apoptosis and phospho-p38 MAPK overexpression. The 25-(OH) D levels were positively correlated with increased peripheral blood neutrophil apoptosis and phospho-p38 MAPK levels. In addition, expression of the phospho-p38 MAPK protein was also positively correlated with peripheral blood neutrophil apoptosis., Conclusion: Our results suggest that 1α,25VitD3 induces peripheral blood neutrophil apoptosis through the p38 MAPK signaling pathway in AECOPD patients.

In this study, cellulose nanofibrils (CNFs) were successfully isolated from coconut palm petiole residues falling off naturally with chemical pretreatments and mechanical treatments by a grinder and a homogenizor. FTIR spectra analysis showed that most of hemicellulose and lignin were removed from the fiber after chemical pretreatments. The compositions of CNFS indicated that high purity of nanofibrils with cellulose contain more than 95% was obtained. X-ray diffractogram demonstrated that chemical pretreatments significantly increased the crystallinity of CNFs from 38.00% to 70.36%; however, 10-15 times of grinding operation followed by homogenizing treatment after the chemical pretreatments did not significantly improve the crystallinity of CNFs. On the contrary, further grinding operation could destroy crystalline regions of the cellulose. SEM image indicated that high quality of CNFs could be isolated from coconut palm petiole residues with chemical treatments in combination of 15 times of grinding followed by 10 times of homogenization and the aspect ratio of the obtained CNFs ranged from 320 to 640. The result of TGA-DTG revealed that the chemical-mechanical treatments improved thermal stability of fiber samples, and the CNFs with 15 grinding passing times had the best thermal stability. This work suggests that the CNFs can be successfully extracted from coconut palm petiole residues and it may be a potential feedstock for nanofiber reinforced composites due to its high aspect ratio and crystallinity.

Organic agriculture requires cultivars that can adapt to organic crop management systems without the use of synthetic pesticides as well as genotypes with improved nutritional value. The aim of this study encompassing 16 experiments was to compare 23 broccoli cultivars for the content of phytochemicals associated with health promotion grown under organic and conventional management in spring and fall plantings in two broccoli growing regions in the US (Oregon and Maine). The phytochemicals quantified included: glucosinolates (glucoraphanin, glucobrassicin, neoglucobrassin), tocopherols (δ-, γ-, α-tocopherol) and carotenoids (lutein, zeaxanthin, β-carotene). For glucoraphanin (17.5%) and lutein (13%), genotype was the major source of total variation; for glucobrassicin, region (36%) and the interaction of location and season (27.5%); and for neoglucobrassicin, both genotype (36.8%) and its interactions (34.4%) with season were important. For δ- and γ-tocopherols, season played the largest role in the total variation followed by location and genotype; for total carotenoids, genotype (8.41-13.03%) was the largest source of variation and its interactions with location and season. Overall, phytochemicals were not significantly influenced by management system. We observed that the cultivars with the highest concentrations of glucoraphanin had the lowest for glucobrassicin and neoglucobrassicin. The genotypes with high concentrations of glucobrassicin and neoglucobrassicin were the same cultivars and were early maturing F1 hybrids. Cultivars highest in tocopherols and carotenoids were open pollinated or early maturing F1 hybrids. We identified distinct locations and seasons where phytochemical performance was higher for each compound. Correlations among horticulture traits and phytochemicals demonstrated that glucoraphanin was negatively correlated with the carotenoids and the carotenoids were correlated with one another. Little or no association between phytochemical concentration and date of cultivar release was observed, suggesting that modern breeding has not negatively influenced the level of tested compounds. We found no significant differences among cultivars from different seed companies.

Background: DNA methyltransferase 3A (DNMT3A) mutations were considered to be independently associated with unfavorable prognosis in adults with de novo acute myeloid leukemia (AML), however, there are still debates on this topic. Here, we aim to further investigate the association between DNMT3A mutations and prognosis of patients with AML., Methods: Eligible studies were identified from several data bases including PubMed, Embase, Web of Science, ClinicalTrials and the Cochrane Library (up to June 2013). The primary endpoint was overall survival (OS), while relapse-free survival (RFS) and event-free survival (EFS) were chosen as secondary endpoints. If possible, we would pool estimate effects (hazard ratio [HR] with 95% confidence interval[CI]) of outcomes in random and fixed effects models respectively., Results: That twelve cohort studies with 6377 patients exploring the potential significance of DNMT3A mutations on prognosis were included. Patients with DNMT3A mutations had slightly shorter OS (HR = 1.60; 95% CI, 1.31-1.95; P<0.001), as compared to wild-type carriers. Among the patients younger than 60 years of age, DNMT3A mutations predicted a worse OS (HR = 1.84; 95% CI, 1.36-2.50; P<0.001). In addition, mutant DNMT3A predicted inferior OS (HR = 2.30; 95% CI, 1.78-2.97; P = 0.862) in patients with unfavorable genotype abnormalities. Similar results were also found in some other subgroups. However, no significant prognostic value was found on OS (HR = 1.40; 95% CI, 0.98-1.99; P = 0.798) in the favorable genotype subgroup. Similar results were found on RFS and EFS under different conditions., Conclusions: DNMT3A mutations have slightly but significantly poor prognostic impact on OS, RFS and EFS of adults with de novo AML in total population and some specific subgroups.

Urotensin II (UII) is a vasoactive peptide composed of 11 amino acids that has been implicated to contribute to the development of cardiovascular disease. The purpose of this study was to investigate whether UII affects the development of atherosclerosis in cholesterol-fed rabbits. UII was infused for 16 weeks through an osmotic mini-pump into male Japanese White rabbits fed on a high-cholesterol diet. Plasma lipids and body weight were measured every 4 weeks. Aortic atherosclerotic lesions along with cellular components, collagen fibers, matrix metalloproteinase-1 and -9 were examined. Moreover, vulnerability index of atherosclerotic plaques was evaluated. UII infusion significantly increased atherosclerotic lesions within the entire aorta by 21% over the control (P = 0.013). Atherosclerotic lesions were increased by 24% in the aortic arch (P = 0.005), 11% in the thoracic aorta (P = 0.054) and 18% in the abdominal aorta (P = 0.035). These increases occurred without changes in plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or body weight. Immunohistochemical staining revealed that macrophages and matrix metalloproteinase-9 were significantly enhanced by 2.2-fold and 1.6-fold in UII group. In vitro studies demonstrated that UII up-regulated the expression of vascular cell adhesion protein-1 and intercellular adhesion molecule-1 in human umbilical vein endothelial cells, which was inhibited by the UII receptor antagonist urantide. In conclusion, our results showed that UII promotes the development of atherosclerotic lesions and destabilizes atherosclerotic plaques in cholesterol-fed rabbits.

Background: No comprehensive analysis is available on the viral etiology and clinical characterization among children with severe acute respiratory infection (SARI) in China during 2009 H1N1 pandemic and post-pandemic period., Methods: Cohort of 370 hospitalized children (1 to 72 months) with SARI from May 2008 to March 2010 was enrolled in this study. Nasopharyngeal aspirate (NPA) specimens were tested by a commercial assay for 18 respiratory viral targets. The viral distribution and its association with clinical character were statistically analyzed., Results: Viral pathogen was detected in 350 (94.29%) of children with SARI. Overall, the most popular viruses were: enterovirus/rhinovirus (EV/RV) (54.05%), respiratory syncytial virus (RSV) (51.08%), human bocavirus (BoCA) (33.78%), human parainfluenzaviruse type 3 (PIV3) (15.41%), and adenovirus (ADV) (12.97%). Pandemic H1N1 was the dominant influenza virus (IFV) but was only detected in 20 (5.41%) of children. Moreover, detection rate of RSV and human metapneumovirus (hMPV) among suburb participants were significantly higher than that of urban area (P<0.05). Incidence of VSARI among suburb participants was also significant higher, especially among those of 24 to 59 months group (P<0.05)., Conclusion: Piconaviruses (EV/RV) and paramyxoviruses are the most popular viral pathogens among children with SARI in this study. RSV and hMPV significantly increase the risk of SARI, especially in children younger than 24 months. Higher incidence of VSARI and more susceptibilities to RSV and hMPV infections were found in suburban patients.

The identification of disease-causing mutations in next-generation sequencing (NGS) data requires efficient filtering techniques. In patients with rare recessive diseases, compound heterozygosity of pathogenic mutations is the most likely inheritance model if the parents are non-consanguineous. We developed a web-based compound heterozygous filter that is suited for data from NGS projects and that is easy to use for non-bioinformaticians. We analyzed the power of compound heterozygous mutation filtering by deriving background distributions for healthy individuals from different ethnicities and studied the effectiveness in trios as well as more complex pedigree structures. While usually more then 30 genes harbor potential compound heterozygotes in single exomes, this number can be markedly reduced with every additional member of the pedigree that is included in the analysis. In a real data set with exomes of four family members, two sisters affected by Mabry syndrome and their healthy parents, the disease-causing gene PIGO, which harbors the pathogenic compound heterozygous variants, could be readily identified. Compound heterozygous filtering is an efficient means to reduce the number of candidate mutations in studies aiming at identifying recessive disease genes in non-consanguineous families. A web-server is provided to make this filtering strategy available at www.gene-talk.de.

Tumor suppressor p53, which is activated by various stress and oncogene activation, is a target for anti-cancer drug development. In this study, by screening panels of protein kinase inhibitors and protein phosphatase inhibitors, we identified 5-Iodotubercidin as a strong p53 activator. 5-Iodotubercidin is purine derivative and is used as an inhibitor for various kinases including adenosine kinase. We found that 5-Iodotubercidin could cause DNA damage, verified by induction of DNA breaks and nuclear foci positive for γH2AX and TopBP1, activation of Atm and Chk2, and S15 phosphorylation and up-regulation of p53. As such, 5-Iodotubercidin induces G2 cell cycle arrest in a p53-dependent manner. Itu also induces cell death in p53-dependent and -independent manners. DNA breaks were likely generated by incorporation of 5-Iodotubercidin metabolite into DNA. Moreover, 5-Iodotubercidin showed anti-tumor activity as it could reduce the tumor size in carcinoma xenograft mouse models in p53-dependent and -independent manners. These findings reveal 5-Iodotubercidin as a novel genotoxic drug that has chemotherapeutic potential.

Introduction: Integration-deficient lentiviral vectors (IDLVs) are a promising platform for immunisation to elicit both humoral immunity and cellular mediated immunity (CMI). Here, we compared the specific immunity in mice immunised via different regimens (homologous and cocktail) with IDLV-based HCV pseudoparticles (HCVpps) carrying pseudotyped glycoproteins E1E2 and bearing the HCV NS3 gene. Humoral and cell-mediated immune responses were also evaluated after IDLV-HCVpp immunisation combined with heterologous rAd5-CE1E2 priming protocols. Sera from the mice effectively elicited anti-E1, -E2, and -NS3 antibody responses, and neutralised various HCVpp subtypes (1a, 1b, 2a, 3a and 5a). No significant CMI was detected in the groups immunised with IDLV-based HCVpps. In contrast, the combination of rAd5-CE1E2 priming and IDLV-based HCVpp boosting induced significant CMI against multiple antigens (E1, E2, and NS3)., Conclusion: IDLV-based HCVpps are a promising vaccination platform and the combination of rAd5-CE1E2 and IDLV-based HCVpp prime-boost strategy should be further explored for the development of a cross-protective HCV vaccine.

Corynebacterium glutamicum lacking the succinate dehydrogenase complex can produce succinate aerobically with acetate representing the major byproduct. Efforts to increase succinate production involved deletion of acetate formation pathways and overexpression of anaplerotic pathways, but acetate formation could not be completely eliminated. To address this issue, we constructed a pathway for recycling wasted carbon in succinate-producing C. glutamicum. The acetyl-CoA synthetase from Bacillus subtilis was heterologously introduced into C. glutamicum for the first time. The engineered strain ZX1 (pEacsA) did not secrete acetate and produced succinate with a yield of 0.50 mol (mol glucose)(-1). Moreover, in order to drive more carbon towards succinate biosynthesis, the native citrate synthase encoded by gltA was overexpressed, leading to strain ZX1 (pEacsAgltA), which showed a 22% increase in succinate yield and a 62% decrease in pyruvate yield compared to strain ZX1 (pEacsA). In fed-batch cultivations, strain ZX1 (pEacsAgltA) produced 241 mM succinate with an average volumetric productivity of 3.55 mM h(-1) and an average yield of 0.63 mol (mol glucose) (-1), making it a promising platform for the aerobic production of succinate at large scale.

Heat shock proteins (Hsps) play important roles in the environmental adaptation of various organisms. To explore the functions of Hsps in relation to heat stress and development in Cotesia vestalis, a solitary larval endoparasitoid of Plutella xylostella, four heat shock protein genes, CvHsp40, CvHsc70, CvHsp70 and CvHsp90, were cloned and sequenced from C. vestalis by real-time quantitative PCR and RACE. The cDNA sequence of CvHsp40, CvHsc70, CvHsp70 and CvHsp90 were 1473 bp, 2316 bp, 2279 bp and 2663 bp long, which encode proteins with calculated molecular weights (MW) of 39.1 kDa, 71.2 kDa, 70.1 kDa and 83.3 kDa, respectively. Furthermore, the analysis of genomic DNA confirmed that no introns existed in CvHsp40, CvHsp70 and CvHsp90 while two introns were present in CvHsc70. The amino acid sequence analysis of CvHsps indicated that CvHsp40 is a Type II Hsp40 homolog, CvHsp70 and CvHsc70 are the eukaryotic cytoplasmic Hsp70s, and CvHsp90 is the β-isoform of Hsp90. The divergent transcriptional patterns of CvHsp40, CvHsp70 and CvHsp90 in the different developmental stages suggested that CvHsp transcripts were under different mechanisms of regulation during the development of parasitoid larvae. The dramatic increase of transcripts of CvHsp70 at the third-instar larva coincided with its developmental change in this stage, that is, from inside host to outside host. CvHsp40, CvHsc70 and CvHsp70 showed a trend of sex-specific differences of transcript abundance in the adult stage. All CvHsp transcripts in different developmental stages were significantly induced by heat stress, and the lowest transcript abundances appeared around the temperature 27°C, which probably suggest that this is the most favorable temperature for the development of C. vestalis. Our results suggest that the expression of heat shock proteins reflects to some extent the developmental changes and environmental requirements of insects.

Maintaining metabolic homeostasis is critical for plant growth and development. Here we report proteome and metabolome changes when the metabolic homeostasis is perturbed due to gene-dosage dependent mutation of Arabidopsis isopropylmalate dehydrogenases (IPMDHs). By integrating complementary quantitative proteomics and metabolomics approaches, we discovered that gradual ablation of the oxidative decarboxylation step in leucine biosynthesis caused imbalance of amino acid homeostasis, redox changes and oxidative stress, increased protein synthesis, as well as a decline in photosynthesis, which led to rearrangement of central metabolism and growth retardation. Disruption of IPMDHs involved in aliphatic glucosinolate biosynthesis led to synchronized increase of both upstream and downstream biosynthetic enzymes, and concomitant repression of the degradation pathway, indicating metabolic regulatory mechanisms in controlling glucosinolate biosynthesis.

Background: Acute respiratory tract infections (ARTIs) represent a serious global health burden. To date, few reports have addressed the prevalence of respiratory viruses (RVs) in adults with ARTIs attending an emergency department (ED). Therefore, the potential impact of respiratory virus infections on such patients remains unknown., Methodology/principal Findings: To determine the epidemiological and clinical profiles of common and recently discovered respiratory viruses in adults with ARTIs attending an ED in Beijing, a 1-year consecutive study was conducted from May, 2010, to April, 2011. Nose and throat swab samples from 416 ARTI patients were checked for 13 respiratory viruses using multiple reverse transcription polymerase chain reaction(RT-PCR) assays for common respiratory viruses, including influenza viruses (Flu) A, B, and adenoviruses (ADVs), picornaviruses (PICs), respiratory syncytial virus (RSV), parainfluenza viruses (PIVs) 1-3, combined with real-time RT-PCR for human metapneumovirus (HMPV) and human coronaviruses (HCoVs, -OC43, -229E, -NL63, and -HKU1). Viral pathogens were detected in 52.88% (220/416) of patient samples, and 7.21% (30/416) of patients tested positive for more than one virus. PICs (17.79%) were the dominant agents detected, followed by FluA (16.11%), HCoVs (11.78%), and ADV (11.30%). HMPV, PIVs, and FluB were also detected (<3%), but not RSV. The total prevalence and the dominant virus infections detected differed significantly between ours and a previous report. Co-infection rates were high for HCoV-229E (12/39, 30.76%), PIC (22/74, 29.73%), ADV (12/47, 25.53%) and FluA (15/67, 22.39%). Different patterns of clinical symptoms were associated with different respiratory viruses., Conclusions: The pattern of RV involvement in adults with ARTIs attending an ED in China differs from that previously reported. The high prevalence of viruses (PIC, FluA, HCoVs and ADV) reported here strongly highlight the need for the development of safe and effective therapeutic approaches for these viruses.

Background and Objectives: Human papillomaviruses have been linked causally to some human cancers such as cervical carcinoma, but there is very little research addressing the effect of HPV infection on human liver cells. We chose the human hepatoma derived cell line Hep G2 to investigate whether HPV gene integration took place in liver cells as well., Methods: We applied PCR to detect the possible integration of HPV genes in Hep G2 cells. We also investigated the expression of the integrated E6 and E7 genes by using RT-PCR and Western blotting. Then, we silenced E6 and E7 expression and checked the cell proliferation and apoptosis in Hep G2 cells. Furthermore, we analyzed the potential genes involved in cell cycle and apoptosis regulatory pathways. Finally, we used in situ hybridization to detect HPV 16/18 in hepatocellular carcinoma samples., Results: Hep G2 cell line contains integrated HPV 18 DNA, leading to the expression of the E6 and E7 oncogenic proteins. Knockdown of the E7 and E6 genes expression reduced cell proliferation, caused the cell cycle arrest at the S phase, and increased apoptosis. The human cell cycle and apoptosis real-time PCR arrays analysis demonstrated E6 and E7-mediated regulation of some genes such as Cyclin H, UBA1, E2F4, p53, p107, FASLG, NOL3 and CASP14. HPV16/18 was found in only 9% (9/100) of patients with hepatocellular carcinoma., Conclusion: Our investigations showed that HPV 18 E6 and E7 genes can be integrated into the Hep G2, and we observed a low prevalence of HPV 16/18 in hepatocellular carcinoma samples. However, the precise risk of HPV as causative agent of hepatocellular carcinoma needs further study.

Both nature and induced regulatory T (Treg) lymphocytes are potent regulators of autoimmune and allergic disorders. Defects in endogenous Treg cells have been reported in patients with allergic asthma, suggesting that disrupted Treg cell-mediated immunological regulation may play an important role in airway allergic inflammation. In order to determine whether adoptive transfer of induced Treg cells generated in vitro can be used as an effective therapeutic approach to suppress airway allergic inflammation, exogenously induced Treg cells were infused into ovalbumin-sensitized mice prior to or during intranasal ovalbumin challenge. The results showed that adoptive transfer of induced Treg cells prior to allergen challenge markedly reduced airway hyperresponsiveness, eosinophil recruitment, mucus hyper-production, airway remodeling, and IgE levels. This effect was associated with increase of Treg cells (CD4(+)FoxP3(+)) and decrease of dendritic cells in the draining lymph nodes, and with reduction of Th1, Th2, and Th17 cell response as compared to the controls. Moreover, adoptive transfer of induced Treg cells during allergen challenge also effectively attenuate airway inflammation and improve airway function, which are comparable to those by natural Treg cell infusion. Therefore, adoptive transfer of in vitro induced Treg cells may be a promising therapeutic approach to prevent and treat severe asthma.

NADPH oxidase-2 (Nox2)/gp91(phox) and p47(phox) deficient mice are prone to hyper-inflammatory responses suggesting a paradoxical role for Nox2-derived reactive oxygen species (ROS) as anti-inflammatory mediators. The molecular basis for this mode of control remains unclear. Here we demonstrate that IFNγ/LPS matured p47(phox-/-)-ROS deficient mouse dendritic cells (DC) secrete more IL-12p70 than similarly treated wild type DC, and in an in vitro co-culture model IFNγ/LPS matured p47(phox-/-) DC bias more ovalbumin-specific CD4(+) T lymphocytes toward a Th1 phenotype than wild type (WT) DC through a ROS-dependent mechanism linking IL-12p70 expression to regulation of p38-MAPK activation. The Nox2-dependent ROS production in DC negatively regulates proinflammatory IL-12 expression in DC by constraining p38-MAPK activity. Increasing endogenous H(2)O(2) attenuates p38-MAPK activity in IFNγ/LPS stimulated WT and p47(phox-/-) DC, which suggests that endogenous Nox 2-derived ROS functions as a secondary messenger in the activated p38-MAPK signaling pathway during IL-12 expression. These findings indicate that ROS, generated endogenously by innate and adaptive immune cells, can function as important secondary messengers that can regulate cytokine production and immune cell cross-talk to control during the inflammatory response.