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BackgroundPulmonary fibrosis (PF) is a common interstitial pneumonia disease, also occurred in post-COVID-19 survivors. The mechanism underlying the anti-PF effect of Qing Fei Hua Xian Decotion (QFHXD), a traditional Chinese medicine formula applied for treating PF in COVID-19 survivors, is unclear. This study aimed to uncover the mechanisms related to the anti-PF effect of QFHXD through analysis of network pharmacology and experimental verification.MethodsThe candidate chemical compounds of QFHXD and its putative targets for treating PF were achieved from public databases, thereby we established the corresponding "herb-compound-target" network of QFHXD. The protein-protein interaction network of potential targets was also constructed to screen the core targets. Furthermore, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict targets, and pathways, then validated by in vivo experiments.ResultsA total of 188 active compounds in QFHXD and 50 target genes were identified from databases. The key therapeutic targets of QFHXD, such as PI3K/Akt, IL-6, TNF, IL-1β, STAT3, MMP-9, and TGF-β1 were identified by KEGG and GO analysis. Anti-PF effects of QFHXD (in a dose-dependent manner) and prednisone were confirmed by HE, Masson staining, and Sirius red staining as well as in vivo Micro-CT and immunohistochemical analysis in a rat model of bleomycin-induced PF. Besides, QFXHD remarkably inhibits the activity of PI3K/Akt/NF-κB and TGF-β1/Smad2/3.ConclusionsQFXHD significantly attenuated bleomycin-induced PF via inhibiting inflammation and epithelial-mesenchymal transition. PI3K/Akt/NF-κB and TGF-β1/Smad2/3 pathways might be the potential therapeutic effects of QFHXD for treating PF.

The aim of this systematic review was to describe the efficacy and acceptability of natural products in the management of oral mucositis caused by radiation. From the day it started to August 7, 2023, a thorough search for randomized controlled trials (RCTs) was carried out among seven databases: the Web of Science, PubMed, Embase, OVID, Scopus, the Cochrane Library and the CINAHL database. Only English-language articles were identified during the search. Using the revised Cochrane risk-of-bias tool, version 2, two researchers screened the articles, collected information on study characteristics, and appraised risks of bias. The data were analyzed and descriptively presented with a narrative synthesis methodology involving the Synthesis Without Meta-Analysis (SWiM) reporting element applied in detail. The PROSPERO registration number of this study is CRD42023476932. Thirty-six clinical trials were included in the study; the included studies included a variety of 20 types of natural products. Honey and Curcuma longa were the most commonly assessed natural products. A total of 2,400 participants reported taking part in therapy with natural products for oral mucositis. Natural products demonstrated substantial efficacy in terms of influencing intensity, incidence, pain score, quality of life, and symptoms such as xerostomia and dysphagia. Except for manuka honey, most natural products were well accepted. Regarding the clinical trials' risk of bias, 2 clinical trials (5.56%) had a high risk of bias, 17 studies (47.2%) had a low risk of bias, and 17 studies (47.2%) were rated with "some concern." Natural remedies work well as alternate treatments for managing oral mucositis caused by radiation therapy. However, additional clinical trials are still needed. The safety of these conventional medications as well as their effectiveness and safety when used in combination with other conventional or naturopathic therapies should be fully examined.

Developing countries are deprived of resources, and their economies are dwindling. Energy shortfall is one of the leading issues in developing countries that not only shatter economies but is the leading cause of depletion of natural resources and environmental pollution. There is an urgent need to shift to renewable energy sources to save economies and natural resources and to save our ecological system. Aiming for this, we have collected a cross-sectional data set to study the household intentions of shifting to wind energy and analysed the moderated mediation interactions of the variable to better understand socio-economic and personal factors. 840 responses were analysed using smart-PLS 4.0; results revealed that cost value and social influence directly relate to renewable energy adoption. Environmental knowledge directly influences attitude towards the environment, and health consciousness influences perceived behavioural control. Results also revealed that social influence strengthens the indirect relationship between awareness of renewable energy and its adoption, while it weakens the indirect relationship between health consciousness and renewable energy adoption.

ObjectiveTo determine the efficacy of three different maternal screening programs (first-trimester screening [FTS], individual second-trimester screening [ISTS], and first- and second-trimester combined screening [FSTCS]) in predicting offspring with trisomy 21, trisomy 18, and neural tube defects (NTDs).MethodsA retrospective cohort involving 108,118 pregnant women who received prenatal screening tests during the first (9-13+6 weeks) and second trimester (15-20+6 weeks) in Hangzhou, China from January-December 2019, as follows: FTS, 72,096; ISTS, 36,022; and FSTCS, 67,631 gravidas.ResultThe high and intermediate risk positivity rates for trisomy 21 screening with FSTCS (2.40% and 5.57%) were lower than ISTS (9.02% and 16.14%) and FTS (2.71% and 7.19%); there were statistically significant differences in the positivity rates among the screening programs (all P < 0.05). Detection of trisomy 21 was as follows: ISTS, 68.75%; FSTCS, 63.64%; and FTS, 48.57%. Detection of trisomy 18 was as follows; FTS and FSTCS, 66.67%; and ISTS, 60.00%. There were no statistical differences in the detection rates for trisomy 21 and 18 among the 3 screening programs (all P > 0.05). The positive predictive values (PPVs) for trisomy 21 and 18 were highest with FTS, while the false positive rate (FPR) was lowest with FSTCS.ConclusionFSTCS was superior to FTS and ISTS screening and substantially reduced the number of high risk pregnancies for trisomy 21 and 18; however, FSTCS was not significantly different in detecting fetal trisomy 21 and 18 and other confirmed cases with chromosomal abnormalities.

When coronavirus disease 2019 (COVID-19) became a pandemic, one of most important questions was whether people who smoke are at more risk of COVID-19 infection. A number of clinical data have been reported in the literature so far, but controversy exists in the collection and interpretation of the data. Particularly, there is a controversial hypothesis that nicotine might be able to prevent SARS-CoV-2 infection. In the present study, motivated by the reported controversial clinical data and the controversial hypothesis, we carried out cytotoxicity assays in Vero E6 cells to examine the potential cytoprotective activity of nicotine against SARS-CoV-2 infection and demonstrated for the first time that nicotine had no significant cytoprotective activity against SARS-CoV-2 infection in these cells.

Fluoride pollution in water has attracted widespread concern worldwide. In this study, an Artemia eggshell-zirconium (Aes-Z) nanocomposite has been used for fluoride removal. Material characterization results showed that nano-ZrO2 was immobilized on the inner surface of the Artemia eggshell, and there was no pore blockage on the composite material. Various parameters influencing on the fluoride removal, including treatment time, composite dosage, pH, initial fluoride concentration, and other anions, were analyzed. The removal efficiency of the composite material was better than that of the single zirconia material. The removal percentage of fluoride reached 93% in 30 min with an initial fluoride concentration of 10 mg/L and a nanocomposite dosage of 8.0 g/L. The composite material had a high removal efficiency for fluoride in the pH region 4.0-10.0. The adsorption of fluoride was not influenced by the common anions (e.g., Cl-, SO42-, and NO3-) in water. The regeneration revealed that the Aes-Z composite material could be reused and remove fluoride effectively in four cycles. The pseudo-second-order rate model adequately represented the adsorption kinetics of the Aes-Z composite material. A possible, defluoridation mechanism of the Aes-Z composite material was also proposed. This study demonstrates that Aes-Z is a promising adsorbent material for fluoride removal.

ObjectiveTo assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo.MethodsWe included randomized controlled trials of oral celecoxib compared with a non-selective NSAID or placebo in rheumatoid arthritis and osteoarthritis patients. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database. Study selection and data extraction were done by two authors independently. The risk of bias was assessed using Cochrane's risk-of-bias Tool for Randomized Trials. The effect size was presented as a risk ratio with their 95% confidence interval.ResultsUntil July 22nd, 2021, our search identified 6279 records from which, after exclusions, 21 trials were included in the meta-analysis. The overall pooled risk ratio for Antiplatelet Trialists Collaboration cardiovascular events for celecoxib compared with any non-selective non-steroid anti-inflammatory drugs was 0.89 (95% confidence interval: 0.80-1.00). The pooled risk ratio for all-cause mortality for celecoxib compared with non-selective non-steroid anti-inflammatory drugs was 0.81 (95% confidence interval: 0.66-0.98). The cardiovascular mortality rate of celecoxib was lower than non-selective non-steroid anti-inflammatory drugs (risk ratio: 0.75, 95% confidence interval: 0.57-0.99). There was no significant difference between celecoxib and non-selective non-steroid anti-inflammatory drugs or placebo in the risk of other cardiovascular events.ConclusionCelecoxib is relatively safe in rheumatoid arthritis and osteoarthritis patients, independent of dose or duration. But it remains uncertain whether this would remain the same in patients treated with aspirin and patients with established cardiovascular diseases.

The combination of a fluorescent reporter and enzymatic reporter provides a flexible and versatile way for the study of diverse biological processes, such as the detection of transcription and translation. Thus, there is an urgent need to develop this novel bifunctional reporter system. This study reports the design, construction, and validation of a new dicistronic mCherry-lacZα reporter system by artificial lac operon and pbr operon models in lacZM15-producing E. coli. It allows two reporter genes to be co-transcribed into a dicistronic mRNA strand, followed by coupled expression of mCherry and lacZα. In artificial lac operons, expression of the downstream lacZα was demonstrated to be positively related to expression of the upstream ORF. In artificial pbr operons, compared with the insertion of downstream full-length lacZ, the insertion of downstream lacZα exerted a slight effect on the response from the upstream mCherry. Furthermore, the downstream lacZα reporter showed stronger response to Pb(II) than the downstream full-length lacZ. Importantly, the response sensitivity of downstream lacZα was still higher than that of upstream mCherry in a dual RFP-lacZα reporter construct. The highly efficient expression profile of the reporter lacZα peptide makes it a preferred downstream reporter in polycistronic constructs. This novel bifunctional reporter system offers a robust tool for biological studies.

Serine hydroxymethyltransferase 2 (SHMT2) converts serine plus tetrahydrofolate (THF) into glycine plus methylene-THF and is upregulated at the protein level in lung and other cancers. In order to better understand the role of SHMT2 in cancer a model system of HeLa cells engineered for inducible over-expression or knock-down of SHMT2 was characterized for cell proliferation and changes in metabolites and proteome as a function of SHMT2. Ectopic over-expression of SHMT2 increased cell proliferation in vitro and tumor growth in vivo. Knockdown of SHMT2 expression in vitro caused a state of glycine auxotrophy and accumulation of phosphoribosylaminoimidazolecarboxamide (AICAR), an intermediate of folate/1-carbon-pathway-dependent de novo purine nucleotide synthesis. Decreased glycine in the HeLa cell-based xenograft tumors with knocked down SHMT2 was potentiated by administration of the anti-hyperglycinemia agent benzoate. However, tumor growth was not affected by SHMT2 knockdown with or without benzoate treatment. Benzoate inhibited cell proliferation in vitro, but this was independent of SHMT2 modulation. The abundance of proteins of mitochondrial respiration complexes 1 and 3 was inversely correlated with SHMT2 levels. Proximity biotinylation in vivo (BioID) identified 48 mostly mitochondrial proteins associated with SHMT2 including the mitochondrial enzymes Acyl-CoA thioesterase (ACOT2) and glutamate dehydrogenase (GLUD1) along with more than 20 proteins from mitochondrial respiration complexes 1 and 3. These data provide insights into possible mechanisms through which elevated SHMT2 in cancers may be linked to changes in metabolism and mitochondrial function.

Guided by parental investment theory and social role theory, this study aimed to understand current contradictory results regarding sex differences in response to infant faces by considering the effect of gender role orientation. We recruited 300 adults in China and asked them to complete an Interest in Infants questionnaire and a Bem Sex Role Inventory and then administered a behavioral assessment that used unfamiliar infant faces with varying expressions (laughing, neutral, and crying) as stimuli to gauge three components of motivation towards infants (i.e., liking, representational responding, and evoked responding). The results demonstrated that sex differences emerged only in self-reported interest in infants, but no difference was found between the sexes in terms of their hedonic reactions to infant faces. Furthermore, femininity was found to correlate with preferences for infants in both verbal and visual tests, but significant interactive effects of feminine traits and sex were found only in the behavioral test. The findings indicated that men's responses to infants were influenced more by their feminine traits than were women's responses, potentially explaining the greater extent to which paternal (vs. maternal) investment is facultative.

Biomedical question answering (QA) represents a growing concern among industry and academia due to the crucial impact of biomedical information. When mapping and ranking candidate snippet answers within relevant literature, current QA systems typically refer to information retrieval (IR) techniques: specifically, query processing approaches and ranking models. However, these IR-based approaches are insufficient to consider both syntactic and semantic relatedness and thus cannot formulate accurate natural language answers. Recently, deep learning approaches have become well-known for learning optimal semantic feature representations in natural language processing tasks. In this paper, we present a deep ranking recursive autoencoders (rankingRAE) architecture for ranking question-candidate snippet answer pairs (Q-S) to obtain the most relevant candidate answers for biomedical questions extracted from the potentially relevant documents. In particular, we convert the task of ranking candidate answers to several simultaneous binary classification tasks for determining whether a question and a candidate answer are relevant. The compositional words and their random initialized vectors of concatenated Q-S pairs are fed into recursive autoencoders to learn the optimal semantic representations in an unsupervised way, and their semantic relatedness is classified through supervised learning. Unlike several existing methods to directly choose the top-K candidates with highest probabilities, we take the influence of different ranking results into consideration. Consequently, we define a listwise "ranking error" for loss function computation to penalize inappropriate answer ranking for each question and to eliminate their influence. The proposed architecture is evaluated with respect to the BioASQ 2013-2018 Six-year Biomedical Question Answering benchmarks. Compared with classical IR models, other deep representation models, as well as some state-of-the-art systems for these tasks, the experimental results demonstrate the robustness and effectiveness of rankingRAE.

Sterol regulatory element-binding protein (SREBP), a highly conserved family of membrane-bound transcription factors, is an essential regulator for cellular cholesterol and lipid homeostasis in mammalian cells. Sre1, the homolog of SREBP in the fission yeast Schizosaccharomyces pombe (S. pombe), regulates genes involved in the transcriptional responses to low sterol as well as low oxygen. Previous study reported that casein kinase 1 family member Hhp2 phosphorylated the Sre1 N-terminal transcriptional factor domain (Sre1N) and accelerated Sre1N degradation, and other kinases might exist for regulating the Sre1 function. To gain insight into the mechanisms underlying the Sre1 activity and to identify additional kinases involved in regulation of Sre1 function, we developed a luciferase reporter system to monitor the Sre1 activity through its binding site called SRE2 in living yeast cells. Here we showed that both ergosterol biosynthesis inhibitors and hypoxia-mimic CoCl2 caused a dose-dependent increase in the Sre1 transcription activity, concurrently, these induced transcription activities were almost abolished in Δsre1 cells. Surprisingly, either AMPKα Subunit Ssp2 deletion or Glycogen Synthase Kinases Gsk3/Gsk31 double deletion significantly suppressed ergosterol biosynthesis inhibitors- or CoCl2-induced Sre1 activity. Notably, the Δssp2Δgsk3Δgsk31 mutant showed further decreased Sre1 activity when compared with their single or double deletion. Consistently, the Δssp2Δgsk3Δgsk31 mutant showed more marked temperature sensitivity than any of their single or double deletion. Moreover, the fluorescence of GFP-Sre1N localized at the nucleus in wild-type cells, but significantly weaker nuclear fluorescence of GFP-Sre1N was observed in Δssp2, Δgsk3Δgsk31, Δssp2Δgsk3, Δssp2Δgsk31 or Δssp2Δgsk3Δgsk31 cells. On the other hand, the immunoblot showed a dramatic decrease in GST-Sre1N levels in the Δgsk3Δgsk31 or the Δssp2Δgsk3Δgsk31 cells but not in the Δssp2 cells. Altogether, our findings suggest that Gsk3/Gsk31 may regulate Sre1N degradation, while Ssp2 may regulate not only the degradation of Sre1N but also its translocation to the nucleus.

The Tibetan Plateau is an important component of the global carbon cycle due to the large permafrost carbon pool and its vulnerability to climate warming. The Tibetan Plateau has experienced a noticeable warming over the past few decades and is projected to continue warming in the future. However, the direction and magnitude of carbon fluxes responses to climate change and elevated CO2 concentration under Representative Concentration Pathways (RCP) scenarios in the Tibetan Plateau grassland are poorly known. Here, we used a calibrated and validated biogeochemistry model, CENTURY, to quantify the contributions of climate change and elevated CO2 on the future carbon budget in the alpine grassland under three RCP scenarios. Though the Tibetan Plateau grassland was projected a net carbon sink of 16 ~ 25 Tg C yr-1 in the 21st century, the capacity of carbon sequestration was predicted to decrease gradually because climate-driven increases in heterotrophic respiration (Rh) (with linear slopes 0.49 ~ 1.62 g C m-2 yr-1) was greater than the net primary production (NPP) (0.35 ~ 1.52 g C m-2 yr-1). However, the elevated CO2 contributed more to plant growth (1.9% ~ 7.3%) than decomposition (1.7% ~ 6.1%), which could offset the warming-induced carbon loss. The interannual and decadal-scale dynamics of the carbon fluxes in the alpine grassland were primarily controlled by temperature, while the role of precipitation became increasingly important in modulating carbon cycle. The strengthened correlation between precipitation and carbon budget suggested that further research should consider the performance of precipitation in evaluating carbon dynamics in a warmer climate scenario.

Melioidosis is a severe infectious disease caused by gram-negative, facultative intracellular pathogen Burkholderia pseudomallei (B. pseudomallei). Although cases are increasing reported from other parts of the world, it is an illness of tropical and subtropical climates primarily found in southeast Asia and northern Australia. Because of a 40% mortality rate, this life-threatening disease poses a public health risk in endemic area. Early detection of B. pseudomallei infection is vital for prognosis of a melioidosis patient. In this study, a novel isothermal recombinase polymerase amplification combined with lateral flow dipstick (LF-RPA) assay was established for rapid detection of B. pseudomallei. A set of primer-probe targeting orf2 gene within the putative type III secretion system (T3SS) cluster genes was generated and parameters for the LF-RPA assay were optimized. Result can be easy visualized in 30 minutes with the limit of detection (LOD) as low as 20 femtogram (fg) (ca. 25.6 copies) of B. pseudomallei genomic DNA without a specific equipment. The assay is highly specific as no cross amplification was observed with Burkholderia mallei, members of the Burkholderia cepacia-complex and 35 non-B. pseudomallei bacteria species. Moreover, isolates from patients in Hainan (N = 19), Guangdong (N = 1), Guangxi (N = 3) province of China as well as in Australia (N = 3) and Thailand (N = 1) were retrospectively confirmed by the newly developed method. LODs for B. pseudomallei-spiked soil and blood samples were 2.1×103 CFU/g and 4.2×103 CFU/ml respectively. The sensitivity of the LF-RPA assay was comparable to TaqMan Real-Time PCR (TaqMan PCR). In addition, the LF-RPA assay exhibited a better tolerance to inhibitors in blood than TaqMan PCR. Our results showed that the LF-RPA assay is an alternative to existing PCR-based methods for detection of B. pseudomallei with a potentiality of early accurate diagnosis of melioidosis at point of care or in-field use.

ObjectiveTo characterize the high-resolution computed tomography (HRCT) pulmonary abnormalities in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.MethodsPulmonary HRCT images were reconstructed from whole-spine computed tomography (CT) images of 67 patients with SAPHO syndrome. HRCT images of 58 healthy controls were also obtained and reviewed. Patients with pneumonia and tuberculosis were excluded. Demographic and clinical data such as gender, age, onset age, disease duration, erythrocyte sedimentation rate (ESR), highly sensitive C-reactive protein (hs-CRP) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were collected from the SAPHO syndrome patients. Demographic characteristics, ESR and hs-CRP data from the healthy controls were also recorded. Student's t test, Mann-Whitney U test, chi-squared test and logistic regression were employed to compare the HRCT findings of the two groups of patients.ResultsThe median age of the SAPHO syndrome patients was 47.0 years, interquartile range [38.0-53.0]; that of the healthy controls was 37.0[30.8-53.8]. From the detailed HRCT evaluations, abnormalities were identified in 45 patients. We found irregular linear opacities in 29 (43.3%) patients, opacities in 22 (32.8%), ground-glass opacity in 11 (16.4%), pleural thickening in 9 (13.4%), solitary nodules in 6 (9%), bronchiectasis in 3 (4.5%), pulmonary bulla in 2 (3%), multiple nodules in 1 (1.5%), and reticular patterns in 1 (1.5%). Compared to the healthy controls, the SAPHO syndrome patients had a significantly higher rate of opacities but a significantly lower percentage of nodules (especially multiple nodules), although the overall rates of abnormal HRCT findings were similar in the two groups. According to the multivariate logistic regression analysis, increased age and BASDAI < 4 were significant predictors of abnormal HRCT findings.ConclusionOur study is the first to address HRCT pulmonary abnormalities in SAPHO syndrome patients. SAPHO syndrome patients have a significantly higher percentage of opacities and a significantly lower rate of pulmonary nodules than healthy controls. BASDAI and age are possible good predictors of abnormal HRCT pulmonary findings.

The postnatal thymus is an efficient microenvironment for T cell specification and differentiation. B cells are also present in the thymus and have been recently shown to impact T cell selection, however, the mechanisms controlling B cell development in the thymus are largely unknown. In Foxn1lacZ mutant mice, down-regulation of Foxn1 expression in thymic epithelial cells beginning 1 week after birth caused a dramatic reduction of T progenitors and an increase of B cell progenitors. This time point is coincident with the switch from fetal to adult-type hematopoietic stem cells (HSCs), which is regulated by the Lin28-Let7 system. We hypothesize that the thymic environment might regulate this process to suppress fetal-type B cell development in the thymus. In this study we show that in the Foxn1lacZ thymus, although the down-regulation of Lin28 in thymocytes was normal, up-regulation of Let-7 was impaired. The failure to up-regulate Let-7 caused a transient increase of Arid3a in B precursors, which is known to promote fetal-type B cell fate. Over-expression of Lin28a in HSCs also reduced Let-7 and promoted Arid3a expression in BM and thymic B progenitors, increasing B cell production in the thymus. The level of Let-7 in thymic B progenitors was up regulated by in vitro co-culture with IL15, Vitamin-D3, and retinoic acid, thus down-regulating Arid3a to promote B cell differentiation. All of these signals were produced in thymic epithelial cells (TECs) related to Let-7 expression in thymic B progenitors, and down-regulated in Foxn1lacZ mutants. Our data show that signals provided by TEC control thymic B cell development by up-regulating Let-7, suppressing Arid3a expression in intrathymic progenitor B cells to limit their proliferation during the neonatal to adult transition.

Hematopoietic stem cells (HSCs) derived from birth through adult possess differing differentiation potential for T or B cell fate in the thymus; neonatal bone marrow (BM) cells also have a higher potential for B cell production in BM compared to adult HSCs. We hypothesized that this hematopoietic-intrinsic B potential might also regulate B cell development in the thymus during ontogeny.Foxn1lacZ mutant mice are a model in which down regulation of a thymic epithelial cell (TEC) specific transcription factor beginning one week postnatal causes a dramatic reduction of thymocytes production. In this study, we found that while T cells were decreased, the frequency of thymic B cells was greatly increased in these mutants in the perinatal period. We used this model to characterize the mechanisms in the thymus controlling B cell development.Foxn1lacZ mutants, T cell committed intrathymic progenitors (DN1a,b) were progressively reduced beginning one week after birth, while thymic B cells peaked at 3-4 weeks with pre-B-II progenitor phenotype, and originated in the thymus. Heterochronic chimeras showed that the capacity for thymic B cell production was due to a combination of higher B potential of neonatal HSCs, combined with a thymic microenvironment deficiency including reduction of DL4 and increase of IL-7 that promoted B cell fate.Our findings indicate that the capacity and time course for thymic B-cell production are primarily controlled by the hematopoietic-intrinsic potential for B cells themselves during ontogeny, but that signals from TECs microenvironment also influence the frequency and differentiation potential of B cell development in the thymus.

Vibrio parahaemolyticus is a leading foodborne pathogen in southeastern China. In this study, 105 strains of V. parahaemolyticus were isolated from fresh seafood in 2013 and 2014. The serotypes, virulence-associated genes and sequence types (STs) of these strains were analyzed. 26 defined serotypes were identified and 69 strains (65.7%) had untypeable O or K antigen. 8 strains (7.6%) had the virulence-associated gene tdh and no strain carried the trh gene. 45.7% (48/105) of isolates contained all four T3SS1 genes and 50% (4/8) tdh+ trh- V. parahaemolyticus isolates lacked at least one of the four tested T3SS2α genes. 105 strains could be categorized into 84 STs and only 3 STs (ST3, ST8, ST675) had appeared in clinical strains. V. parahaemolyticus strains from seafood have more diverse and untypeable serotypes, less virulence-associated genes and more STs than strains from clinical sources.

Deep learning techniques, e.g., Convolutional Neural Networks (CNNs), have been explosively applied to the research in the fields of information retrieval and natural language processing. However, few research efforts have addressed semantic indexing with deep learning. The use of semantic indexing in the biomedical literature has been limited for several reasons. For instance, MEDLINE citations contain a large number of semantic labels from automatically annotated MeSH terms, and for a great deal of the literature, only the information of the title and the abstract is readily available. In this paper, we propose a Boltzmann Convolutional neural network framework (B-CNN) for biomedicine semantic indexing. In our hybrid learning framework, the CNN can adaptively deal with features of documents that have sequence relationships, and can capture context information accordingly; the Deep Boltzmann Machine (DBM) merges global (the entity in each document) and local information through its training with undirected connections. Additionally, we have designed a hierarchical coarse to fine style indexing structure for learning and classifying documents, and a novel feature extension approach with word sequence embedding and Wikipedia categorization. Comparative experiments were conducted for semantic indexing of biomedical abstract documents; these experiments verified the encouraged performance of our B-CNN model.

A growing understanding of the molecular interactions between immune effector cells and target tumor cells, coupled with refined gene therapy approaches, are giving rise to novel cancer immunotherapeutics with remarkable efficacy in the clinic against both solid and liquid tumors. While immunotherapy holds tremendous promise for treatment of certain cancers, significant challenges remain in the clinical translation to many other types of cancers and also in minimizing adverse effects. Therefore, there is an urgent need for functional potency assays, in vitro and in vivo, that could model the complex interaction of immune cells with tumor cells and can be used to rapidly test the efficacy of different immunotherapy approaches, whether it is small molecule, biologics, cell therapies or combinations thereof. Herein we report the development of an xCELLigence real-time cytolytic in vitro potency assay that uses cellular impedance to continuously monitor the viability of target tumor cells while they are being subjected to different types of treatments. Specialized microtiter plates containing integrated gold microelectrodes enable the number, size, and surface attachment strength of adherent target tumor cells to be selectively monitored within a heterogeneous mixture that includes effector cells, antibodies, small molecules, etc. Through surface-tethering approach, the killing of liquid cancers can also be monitored. Using NK92 effector cells as example, results from RTCA potency assay are very well correlated with end point data from image-based assays as well as flow cytometry. Several effector cells, i.e., PBMC, NK, CAR-T were tested and validated as well as biological molecules such as Bi-specific T cell Engagers (BiTEs) targeting the EpCAM protein expressed on tumor cells and blocking antibodies against the immune checkpoint inhibitor PD-1. Using the specifically designed xCELLigence immunotherapy software, quantitative parameters such as KT50 (the amount of time it takes to kill 50% of the target tumor cells) and % cytolysis are calculated and used for comparing the relative efficacy of different reagents. In summary, our results demonstrate the xCELLigence platform to be well suited for potency assays, providing quantitative assessment with high reproducibility and a greatly simplified work flow.

How to evaluate driver spontaneous reactions in various collision patterns in a quantitative way is one of the most important topics in vehicle safety. Firstly, this paper constructs representative numerical crash scenarios described by impact velocity, impact angle and contact position based on finite element (FE) computation platform. Secondly, a driver cabin model is extracted and described in the well validated multi-rigid body (MB) model to compute the value of weighted injury criterion to quantitatively assess drivers' overall injury under certain circumstances. Furthermore, based on the coupling of FE and MB, parametric studies on various crash scenarios are conducted. It is revealed that the WIC (Weighted Injury Criteria) value variation law under high impact velocities is quite distinct comparing with the one in low impact velocities. In addition, the coupling effect can be elucidated by the fact that the difference of WIC value among three impact velocities under smaller impact angles tends to be distinctly higher than that under larger impact angles. Meanwhile, high impact velocity also increases the sensitivity of WIC under different collision positions and impact angles. Results may provide a new methodology to quantitatively evaluate driving behaviors and serve as a significant guiding step towards collision avoidance for autonomous driving vehicles.

Drought is the most important factor that limits rice production in drought-prone environments. Plant microRNAs (miRNAs) are involved in biotic and abiotic stress responses. Common wild rice (Oryza rufipogon Griff.) contains abundant drought-resistant genes, which provide an opportunity to explore these excellent resources as contributors to improve rice resistance, productivity, and quality.In this study, we constructed four small RNA libraries, called CL and CR from PEG6000-free samples and DL and DR from PEG6000-treated samples, where 'R' indicates the root tissue and 'L' indicates the shoot tissue. A total of 200 miRNAs were identified to be differentially expressed under the drought-treated conditions (16% PEG6000 for 24 h), and the changes in the miRNA expression profile of the shoot were distinct from those of the root. At the miRNA level, 77 known miRNAs, which belong to 23 families, including 40 up-regulated and 37 down-regulated in the shoot, and 85 known miRNAs in 46 families, including 65 up-regulated and 20 down-regulated in the root, were identified as differentially expressed. In addition, we predicted 26 new miRNA candidates from the shoot and 43 from the root that were differentially expressed during the drought stress. The quantitative real-time PCR analysis results were consistent with high-throughput sequencing data. Moreover, 88 miRNAs that were differentially-expressed were predicted to match with 197 targets for drought-stress.Our results suggest that the miRNAs of O. rufipogon are responsive to drought stress. The differentially expressed miRNAs that are tissue-specific under drought conditions could play different roles in the regulation of the auxin pathway, the flowering pathway, the drought pathway, and lateral root formation. Thus, the present study provides an account of tissue-specific miRNAs that are involved in the drought adaption of O. rufipogon.

RPS6KB1 is the kinase of ribosomal protein S6 which is 70 kDa and is required for protein translation. Although the abnormal activation of RPS6KB1 has been found in types of diseases, its role and clinical significance in non-small cell lung cancer (NSCLC) has not been fully investigated. In this study, we identified that RPS6KB1 was over-phosphorylated (p-RPS6KB1) in NSCLC and it was an independent unfavorable prognostic marker for NSCLC patients. In spite of the frequent expression of total RPS6KB1 and p-RPS6KB1 in NSCLC specimens by immunohistochemical staining (IHC), only p-RPS6KB1 was associated with the clinicopathologic characteristics of NSCLC subjects. Kaplan-Meier survival analysis revealed that the increased expression of p-RPS6KB1 indicated a poorer 5-year overall survival (OS) for NSCLC patients, while the difference between the positive or negative RPS6KB1 group was not significant. Univariate and multivariate Cox regression analysis was then used to confirm the independent prognostic value of p-RPS6KB1. To illustrate the underlying mechanism of RPS6KB1 phosphorylation in NSCLC, LY2584702 was employed to inhibit the RPS6KB1 phosphorylation specifically both in lung adenocarcinoma cell line A549 and squamous cell carcinoma cell line SK-MES-1. As expected, RPS6KB1 dephosphorylation remarkably suppressed cells proliferation in CCK-8 test, and promoted more cells arresting in G0-G1 phase by cell cycle analysis. Moreover, apoptotic A549 cells with RPS6KB1 dephosphorylation increased dramatically, with an elevating trend in SK-MES-1, indicating a potential involvement of RPS6KB1 phosphorylation in inducing apoptosis. In conclusion, our data suggest that RPS6KB1 is over-activated as p-RPS6KB1 in NSCLC, rather than just the total protein overexpressing. The phosphorylation level of RPS6KB1 might be used as a novel prognostic marker for NSCLC patients.

Ovarian cancer's poor progression is closely associated with overexpression of matrix metalloproteinase 9 (MMP-9), which belongs to the class of enzymes believed to be involved in the degradation of extracellular matrix. However, the mechanisms underlying regulation of MMP-9 are not completely understood. STAT (signal transducer and activator of transcription) family of transcription factors is well known to be engaged in diverse cellular functions. Activation of STAT3 has been observed in a number of cancers, promoting tumorigenesis and metastasis via transcriptional activation of its target genes. In this study, we tested our hypothesis that STAT3 regulates MMP-9 gene expression in epithelial ovarian cancer. Using epithelial ovarian cancer cell lines as in vitro model, we show an abundance of phosphorylated STAT3 at Tyr705 (p-STAT3) in SKOV3 cell line. We further show that MMP-9 gene promoter was significantly enriched by p-STAT3, and IL-6 treatment led to a significant increase of MMP-9 at mRNA and protein levels, in addition to an association of p-STAT3 with MMP-9 gene. By using luciferase reporter assay, we determined that the STAT3 DNA responsive element of MMP-9 was sufficient to regulate transcriptional activity of a heterologous promoter. These results suggest that the phosphorylation of STAT3 regulates MMP-9 production in ovarian cancer, which might be responsible for its invasiveness and metastasis.

BACKGROUND:Physical performance is an important healthy factor in elder people. Good living habits, which include sleep, can maintain physical strength and physical performance. The aim of the present study was to conduct a cross-sectional study to determine the association between total sleep duration and physical performance. METHODS:Our study population comprised residents of the township central hospital in the suburban of Tianjin, China. We measured muscle strength, walk speed and balance function by grip, 4-m walk test and timed up and go test (TUGT). We divided sleep duration into four groups 8-9h, >9h. RESULTS:A total 898 participants had completed data (392 men and 506 women, mean age 67.71 years). In man, adjusted sleep duration was associated with lower grip in > 9 h group, the mean value (95% CI) was 0.429 (0.409, 0.448), and longer TUGT time was also associated with long sleep duration, 10.46s (9.97 s, 10.95 s). In women, adjusted slower 4-m walk speed present an inverse U-shaped relation with sleep duration, by 0.93 m/s (0.86 m/s, 0.98 m/s), 0.97 m/s (0.96 m/s, 1.00 m/s), 0.97 m/s (0.95 m/s, 0.99 m/s) and 0.92 m/s (0.89 m/s, 0.96 m/s); longer TUGT time were associated with long sleep duration (> 9 h), by 11.23 s (10.70 s, 11.77 s). CONCLUSION:In Chinese community-dwelling elderly, lower muscle strength and lower balance function were associated with long sleep duration in men. Slower walk speed and lower balance function were associated with long sleep duration in women.

Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic liver disease while the biochemical characteristic is the elevated level of total bile acid (TBA). The present study investigated whether miR-148a mediates the induced effect of estrogen on the development of ICP and the proper mechanism: PXR/MRP3 signal pathway. mRNA expression was detected by qPCR, protein expression was detected by western blotting, the concentration of estrogen and TBA were detected by reagent kit respectively. In the cinical research, it was found that miR-148a expression was positive related with the concentration of TBA in the serum of ICP patients. In in vitro research, estradiol (500 nmol/L, 12 h) significantly upregulated miR-148a expression and LV-148a-siRNA inhibited the function of estradiol (500 nmol/L, 48 h) on TBA secretion. In addition, gene silence of miR-148a upregulated PXR expression which was inhibited by estradiol in LO2 cells. Pretreatment of rifampin (10 μmol/L), the agonist of PXR alleviated the TBA secretion induced by estradiol (500 nmol/L, 48 h). miR-148a-siRNA and PXR had a synergistic action on TBA secretion of LO2. Both of miR-148a-siRNA and rifampin (10 μmol/L) inhibited the upregulated effect of estradiol on MRP3 expression. This research has demonstrated that miR-148a may be involved in the induction of estrogen on ICP via PXR signal pathway, and MRP3 may be involved.

It is difficult to study bone in vitro because it contains various cell types that engage in cross-talk. Bone biologically links various organs, and it has thus become increasingly evident that skeletal physiology must be studied in an integrative manner in an intact animal. We developed a model using local intraosseous small interfering RNA (siRNA) injection to rapidly assess the effects of a target gene on the local skeletal environment. In this model, 160-g male Sprague-Dawley rats were treated for 1-2 weeks. The left tibia received intraosseous injection of a parathyroid hormone 1 receptor (Pth1r) or insulin-like growth factor 1 receptor (Igf-1r) siRNA transfection complex loaded in poloxamer 407 hydrogel, and the right tibia received the same volume of control siRNA. All the tibias received an intraosseous injection of recombinant human parathyroid hormone (1-34) (rhPTH (1-34)) or insulin-like growth factor-1 (IGF-1). Calcein green and alizarin red were injected 6 and 2 days before euthanasia, respectively. IGF-1R and PTH1R expression levels were detected via RT-PCR assays and immunohistochemistry. Bone mineral density (BMD), microstructure, mineral apposition rates (MARs), and strength were determined by dual-energy X-ray absorptiometry, micro-CT, histology and biomechanical tests. The RT-PCR and immunohistochemistry results revealed that IGF-1R and PTH1R expression levels were dramatically diminished in the siRNA-treated left tibias compared to the right tibias (both p

Since the early 1980s, the one-child policy has been implemented nationwide in China. A special group called the "only-child-lost family" (OCL family) has emerged and has become a social phenomenon that cannot be ignored. We report latent profiles of posttraumatic growth and their relation to differences in resilience among OCL people in China.A total of 222 OCL people were investigated using the Posttraumatic Growth Inventory and the Connor-Davidson Resilience Scale. Latent profile analysis was applied to explore PTG latent profiles. Multinomial logistic regression was used to analyze the socio-demographic variables in each latent profile and the association between profile membership and resilience.Three latent profiles were identified and labeled the "high appreciation-power group" (30.6%), the "general moderate growth group" (47.7%) and the "low growth and extreme possibility group" (21.7%). Compared to those in the high appreciation-power group, individuals with monthly income >2000 ($312) were less likely to be in the general moderate growth group (OR = 0.13, P

Silkworm cocoons are multi-layered composite structures comprised of high strength silk fiber and sericin, and their mechanical properties have been naturally selected to protect pupas during metamorphosis from various types of external attacks. The present study attempts to gain a comprehensive understanding of the mechanical properties of cocoon shell materials from wild silkworm species Antheraea pernyi under dynamic loading rates. Five dynamic strain rates from 0.00625 s-1 to 12.5 s-1 are tested to show the strain rate sensitivity of the cocoon shell material. In the meantime, the anisotropy of the cocoon shell is considered and the cocoon shell specimens are cut along 0°, 45° and 90° orientation to the short axis of cocoons. Typical mechanical properties including Young's modulus, yield strength, ultimate strength and ultimate strain are extracted and analyzed from the stress-strain curves. Furthermore, the fracture morphologies of the cocoon shell specimens are observed under scanning electron microscopy to help understand the relationship between the mechanical properties and the microstructures of the cocoon material. A discussion on the dynamic strain rate effect on the mechanical properties of cocoon shell material is followed by fitting our experimental results to two previous models, and the effect could be well explained. We also compare natural and dried cocoon materials for the dynamic strain rate effect and interestingly the dried cocoon shells show better overall mechanical properties. This study provides a different perspective on the mechanical properties of cocoon material as a composite material, and provides some insight for bio-inspired engineering materials.

In China, B. burgdorferi, B.garinii, B. afzelii and B. yangtze sp. nov have been reported; B.garinii and B. afzelii are the main pathogenic genotypes. But until now only one Chinese strain was reported with whole genome sequence. In order to further understand the genomic characteristics and diversity of Chinese Borrelia strains, 5 isolates from China were sequenced and compared with the whole genome sequences of strains in other areas. The results showed a high degree of conservation within the linear chromosome of Chinese strains, whereas plasmid showed a much larger diversity according to the majority genomic information of plasmids. The genome sequences of the five Chinese strains were compared with the corresponding reference strains, respectively, according to the genospecies. Pairwise analysis demonstrates that there are only 70 SNPs between the genomes of CS4 and B31. However, there are many more SNPs between the genomes of QX-S13 and VS116, PD91 and PBi, FP1 and PKo, R9 and Pko, respectively. Gene comparison showed some important different genes. OspA was one of the important different genes. Comparative genomic studies have found that OspA gene sequences of PD91 and R9 had great differences compared with the sequence of B31. OspA gene sequence of R9 had a 96bp deletion; OspA gene of PD91 had two deletions: 9bp and 10 bp. To conclude, we showed the genomic characteristics of four genotype Chinese B. burgdorferi strains. The genomic sequence of B. yangtze sp. nov and differences from B. valaisiana were first reported. Comparative analysis of Chinese strains with the different Borrelia species from other areas will help us to understand evolution and pathogenesis of Chinese Borrelia burgdorferi strains.

Irisin, a newly discovered myokine, is considered as a promising candidate for the treatment of metabolic disturbances and cardiovascular diseases. In the present study, we used two animal models, apolipoprotein E-deficient mice fed on a high-cholesterol diet and a mouse carotid partial ligation model to test the anti-atherosclerotic effect of irisin. Irisin treatment (0.5 μg/g body weight/day) significantly reduced the severity of aortic atherosclerosis in apolipoprotein E-deficient mice fed on a high-cholesterol diet and suppressed carotid neointima formation in a carotid partial ligation model. It was associated with decreased inflammation and cell apoptosis in aortic tissues. In addition, in a cell culture model, irisin restored ox-LDL-induced human umbilical vein endothelial cell dysfunction by reducing the levels of inflammatory genes via inhibiting the reactive oxygen species (ROS)/ p38 MAPK/ NF-κB signaling pathway activation and inhibiting cell apoptosis via up-regulating Bcl-2 and down-regulating Bax and caspase-3 expression. Our study demonstrated that irisin significantly reduced atherosclerosis in apolipoprotein E-deficient mice via suppressing ox-LDL-induced cell inflammation and apoptosis, which might have a direct therapeutic effect on atherosclerotic diseases.

For multi-level spondylolysis patients, surgeons commonly choose to fix all the segments with pars interarticularis defect even those without slippage and not responsible for clinical symptoms. In this study, we tried to study the necessity of the preventative long-segment surgery for the defected segment without slippage in treatment of multi-level spondylolysis patients from a biomechanical perspective.We established a bi-level spondylolysis model with pars defects at L4 and L5 segments, and simulated posterior lumbar interbody fusion (PLIF) and pedicle screw fixation at L5-S1 level. Then we compared the biomechanical changes at L4 segment before and after surgery in neutral, flexion, extension, lateral bending and axial rotation position.The stress on L4 pars interarticularis was very similar before and after surgery, and reached the highest in axial rotation. The L3-L4 intradiscal pressure was almost the same, while L4-L5 intradiscal pressure changed a little in lateral bending (increase from 1.993 to 2.160 MPa) and axial rotation (decrease from 1.639 to 1.307 MPa) after surgery. The PLIF surgery caused a little increase of range of motion at adjacent L4-L5 and L3-L4 levels, but the change is very tiny (1 degree).The PLIF surgery will not cause significant biomechanical change at adjacent segment with pars defect in multi-level spondylolysis. On the contrary, excessive long-segment surgery will damage surrounding soft tissues which are important for maintaining the stability of spine. So a preventative long-segment surgery is not necessary for multi-level spondylolysis as long as there are no soft tissue degeneration signs at adjacent level.

Effective book search has been discussed for decades and is still future-proof in areas as diverse as computer science, informatics, e-commerce and even culture and arts. A variety of social information contents (e.g, ratings, tags and reviews) emerge with the huge number of books on the Web, but how they are utilized for searching and finding books is seldom investigated. Here we develop an Integrated Search And Recommendation Technology (IsArt), which breaks new ground by providing a generic framework for searching books with rich social information. IsArt comprises a search engine to rank books with book contents and professional metadata, a Generalized Content-based Filtering model to thereafter rerank books with user-generated social contents, and a learning-to-rank technique to finally combine a wide range of diverse reranking results. Experiments show that this technology permits embedding social information to promote book search effectiveness, and IsArt, by making use of it, has the best performance on CLEF/INEX Social Book Search Evaluation datasets of all 4 years (from 2011 to 2014), compared with some other state-of-the-art methods.

To evaluate the cyclic fatigue resistance and the force generated by OneShape files during preparation of simulated curved canals.Six OneShape files (the test) and six ProTaper F2 files (the control) were subject to the bending ability test. Another thirty files of each type were used to prepare artificial canals (n = 60), which were divided into 3 groups according to respective curvatures of the canals (30°, 60°, and 90°). The numbers of cycles to fatigue (NCF) as well as the positive and negative forces that were generated by files during canal preparation were recorded. The scanning electron microscopy was applied to detect the fracture surfaces.Compared with ProTaper F2 files, the bending loads of OneShape files were significantly lower at deflections of 45°(P < .05), 60° (P < .05) and 75° (P < .01). No significant difference was found at 30°. OneShape files presented a higher NCF in both 60° and 90° canals than the control (P < .01). No significant difference of NCF was found between OneShape and ProTaper files in 30° canals. During the preparation of 30° canals by both files, the negative forces were dominant. With the increase of the curvature, more positive forces were observed. When the OneShape Files were compared with the control, significant different forces were found at D3 and D2 (P < .05) in 30° canals, at D2 (P < .05), D1 (P < .01) and D0 (P < .01) in 60° canals, and at D4 and D3 (P < .01) in 90° canals.OneShape files possessed a reliable flexibility and cyclic fatigue resistance. According to the assessments of the forces generated by files, OneShape instruments performed in a more fatigue-resistant way during curved canal preparation, compared with the ProTaper F2 files.

Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients.

BACKGROUND:Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1) is integral to the vitamin D metabolic pathway. The enzyme catalyzes localized conversion of pro-hormone 25-hydroxyvitamin D3 to active 1,25-dihydroxyvitamin D3. Our aim was to investigate the expression of CYP27B1 at the fetal-maternal interface in the first trimester pregnancy and to determine whether CYP27B1 was associated with recurrent miscarriage (RM). METHODS:Expressions of CYP27B1 mRNA and protein in villi and decidua from 20 women undergoing primary miscarriage, 20 women with RM and 20 women with normal pregnancy were evaluated by western blot, and quantitative real-time PCR. The co-localization of CYP27B1 and certain cytokines including IL-10, IFN-γ, TNF-α, and IL-2 expression were examined using immunohistochemistry and confocal microscopy. RESULTS:Women with RM had a significantly lower expression of CYP27B1 mRNA and protein in villous and decidual tissues compared with the normal pregnant women (P = 0.000 in villus, P = 0.002 in decidua for mRNA; P = 0.036 in villus, P = 0.007 in decidua for protein.). Compared with the normal pregnancy, immunostaining for CYP27B1 was significantly decreased in villous trophoblasts and decidual glandular epithelial cells in RM women. No significant differences in the localization of CYP27B1, IL-10, IFN-γ, TNF-α, and IL-2 expression were identified between the normal pregnant and RM women. CONCLUSIONS:Women with RM have a lower level of CYP27B1 expression in chorionic villi and decidua compared with normal pregnant women, suggesting that reduced CYP27B1 expression may be associated with RM. The consistent localization of CYP27B1 and IL-10, IFN-γ, TNF-α, and IL-2 expression in villous and decidual tissues suggests the importance of the local production of 1,25(OH)2D3 at the fetal-maternal interface to regulate cytokine responses.

The Sanjiang Plain has been experienced significant wetland loss due to expanded agricultural activities, and will be potentially restored by the China National Wetland Conservation Action Plan (NWCP) in future. The objective of this study is to evaluate the impact of future climate warming and wetland restoration on wetland CH4 emissions in northeast China. We used an atmosphere-vegetation interaction model (AVIM2) to drive a modified biogeophysical model (CH4MODwetland), and projected CH4 flux variations from the Sanjiang Plain wetlands under different Representative Concentration Pathway scenarios throughout the 21st century. Model validation showed that the regressions between the observed and simulated CH4 fluxes by the modified model produced an R2 of 0.49 with a slope of 0.87 (p

BACKGROUND:Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA molecules. The transposon-derived piRNA prediction can enrich the research contents of small ncRNAs as well as help to further understand generation mechanism of gamete. METHODS:In this paper, we attempt to differentiate transposon-derived piRNAs from non-piRNAs based on their sequential and physicochemical features by using machine learning methods. We explore six sequence-derived features, i.e. spectrum profile, mismatch profile, subsequence profile, position-specific scoring matrix, pseudo dinucleotide composition and local structure-sequence triplet elements, and systematically evaluate their performances for transposon-derived piRNA prediction. Finally, we consider two approaches: direct combination and ensemble learning to integrate useful features and achieve high-accuracy prediction models. RESULTS:We construct three datasets, covering three species: Human, Mouse and Drosophila, and evaluate the performances of prediction models by 10-fold cross validation. In the computational experiments, direct combination models achieve AUC of 0.917, 0.922 and 0.992 on Human, Mouse and Drosophila, respectively; ensemble learning models achieve AUC of 0.922, 0.926 and 0.994 on the three datasets. CONCLUSIONS:Compared with other state-of-the-art methods, our methods can lead to better performances. In conclusion, the proposed methods are promising for the transposon-derived piRNA prediction. The source codes and datasets are available in S1 File.

Pretreatment plasma D-dimer levels have been reported to predict survival in several types of malignancies. The aim of this study was to evaluate the prognostic value of D-dimer levels in patients with newly diagnosed natural killer/T-cell lymphoma (NKTCL). The cut-off value of D-dimer to predict survival was set as 1.2 μg/mL based on the receiver operating curve analysis. Patients with a D-dimer level ≥ 1.2 μg/mL had significantly more adverse clinical features, including poor performance status, advanced stage diseases, B symptoms, elevated serum lactic dehydrogenase levels, involvement of regional lymph nodes, more extranodal diseases, and higher International Prognostic Index and natural killer/T-cell lymphoma prognostic index scores. A D-dimer level ≥ 1.2 μg/mL was significantly associated with inferior 3-year overall survival (OS, 13.0 vs. 68.5%, P < 0.001). In the multivariate analysis, a D-dimer level ≥ 1.2 μg/mL remained an independent predictor for worse OS (HR: 3.13, 95% CI: 1.47-6.68, P = 0.003) after adjusting for other confounding prognostic factors. Among patients with Ann Arbor stage I-II diseases, those with a D-dimer level ≥ 1.2 μg/mL had a significantly worse survival than those with a D-dimer level < 1.2 μg/mL (3 year-OS: 76.2 vs. 22.2%, P < 0.001). Survival of early-stage patients with a high D-dimer level was similar to that of the advanced-stage patients. In conclusion, pretreatment plasma D-dimer level may serve as a simple but effective predictor of prognosis in patients with NKTCL.

Mazus sunhangii, a new species of Mazaceae from central China is described and illustrated based on evidence from morphology and molecular phylogeny. This new species is morphologically similar to M. puchellus and M. omeiensis but differs in erect habit, inflorescence position, leaf pattern and corolla color. Phylogenetic analysis based on four chloroplast DNA regions (rbcL, rps16, trnL-F, and psbA-trnH) identified the new species as the independent lineage sister to the other East Asian Mazus species. The new species is known only from a single location in Mt. Shennongjia area in northwest Hubei province, at the elevation of 760 m. The species grows on the limestone cliff, and, because a tourist arterial highway is located along this cliff, its habitat can be easily disturbed or destroyed. We propose that the only known species location is recognized as critical habitat (i.e., as the habitat required to ensure the persistence of a species) and the species listed as Critically Endangered based on the International Union for Conservation of Nature Red List Categories and Criteria B2a.

Serine carboxypeptidase (SCP) is one of the largest groups of enzymes catalyzing proteolysis for functional protein maturation. To date, little is known about the function of SCPs in rice. In this study, we present a comprehensive analysis of the gene structure and expression profile of 59 rice SCPs. SCP46 is dominantly expressed in developing seeds, particularly in embryo, endosperm and aleurone layers, and could be induced by ABA. Functional characterization revealed that knock-down of SCP46 resulted in smaller grain size and enhanced seed germination. Furthermore, scp46 seed germination became less sensitive to the ABA inhibition than the Wild-type did; suggesting SCP46 is involved in ABA signaling. As indicated by RNA-seq and qRT-PCR analysis, numerous grain filling and seed dormancy related genes, such as SP, VP1 and AGPs were down-regulated in scp46. Yeast-two-hybrid assay also showed that SCP46 interacts with another ABA-inducible protein DI19-1. Taken together, we suggested that SCP46 is a master regulator of grain filling and seed germination, possibly via participating in the ABA signaling. The results of this study shed novel light into the roles of SCPs in rice.

For the analysis of interior geometry and property changes of a large-sized analog model during a loading or other medium (water or oil) injection process with a non-destructive way, a consecutive X-ray computed tomography (XCT) short-scan method is developed to realize an in-situ tomography imaging. With this method, the X-ray tube and detector rotate 270° around the center of the guide rail synchronously by switching positive and negative directions alternately on the way of translation until all the needed cross-sectional slices are obtained. Compared with traditional industrial XCTs, this method well solves the winding problems of high voltage cables and oil cooling service pipes during the course of rotation, also promotes the convenience of the installation of high voltage generator and cooling system. Furthermore, hardware costs are also significantly decreased. This kind of scanner has higher spatial resolution and penetrating ability than medical XCTs. To obtain an effective sinogram which matches rotation angles accurately, a structural similarity based method is applied to elimination of invalid projection data which do not contribute to the image reconstruction. Finally, on the basis of geometrical symmetry property of fan-beam CT scanning, a whole sinogram filling a full 360° range is produced and a standard filtered back-projection (FBP) algorithm is performed to reconstruct artifacts-free images.

To investigate the seasonal and interannual dynamics of dissolved organic matter (DOM) in the Yangtze Estuary, surface and bottom water samples in the Yangtze Estuary and its adjacent sea were collected and characterized using fluorescence excitation-emission matrices (EEMs) and parallel factor analysis (PARAFAC) in both dry and wet seasons in 2012 and 2013. Two protein-like components and three humic-like components were identified. Three humic-like components decreased linearly with increasing salinity (r>0.90, p

Bone tissue engineering shows good prospects for mandibular reconstruction. In recent studies, prefabricated tissue-engineered bone (PTEB) by recombinant human bone morphogenetic proteins (rhBMPs) applied in vivo has found to be an effective alternative for autologous bone grafts. However, the optimal time to transfer PTEB for mandibular reconstruction is still not elucidated. Thus, here in an animal experiment of rhesus monkey, the suitable transferring time for PTEB to reconstruct mandibular defects was evaluated by 99mTc-MDP SPECT/CT, and its value in monitoring orthotopic rhBMP-2 implants for mandibular reconstruction was also evaluated. The result of SPECT/CT showed higher 99mTc-MDP uptake, indicating osteoinductivity, in rhBMP-2 incorporated demineralized freeze-dried bone allograft (DFDBA) and coralline hydroxyapatite (CHA) implants than those without BMP stimulation. 99mTc-MDP uptake of rhBMP-2 implant peaked at 8 weeks following implantation while CT showed the density of these implants increased after 13 weeks' prefabrication. Histology confirmed that mandibular defects were repaired successfully with PTEB or orthotopically rhBMP-2 incorporated CHA implants, in accordance with SPECT/CT findings. Collectively, data shows 99mTc-MDP SPECT/CT is a sensitive and noninvasive tool to monitor osteoinductivity and bone regeneration of PTEB and orthotopic implants. The PTEB achieved peak osteoinductivity and bone density at 8 to 13 weeks following ectopic implantation, which would serve as a recommendable time frame for its transfer to mandibular reconstruction.

Physical performance is reported to have various beneficial effects on human health, especially in older individuals. Although such effects are associated with body mass index (BMI), the relationship between BMI and physical performance has not been clarified.We conducted a cross-sectional study of 966 suburb-dwelling Tianjin individuals aged ≥ 60 years (average age 67.5±6.02, men 435, women 531). Mobility, balance, and muscle strength were assessed by walking speed, timed up-and-go test (TUGT), and grip strength, respectively. The subjects were categorized into three groups based on BMI (kg/m2) as follows: normal weight, 18.5 ≤ BMI ≤ 23.9; overweight, 24.0 ≤ BMI ≤ 27.9; and obese, BMI ≥ 28.0.After adjusting for all other variables, relative grip strength decreased when BMI increased in both men and women (P for trend

The biomechanical characteristics of midshaft clavicular fractures treated with titanium elastic nail (TEN) is unclear. This study aimed to present a biomechanical finite element analysis of biomechanical characteristics involved in TEN fixation and reconstruction plate fixation for midshaft clavicular fractures.Finite element models of the intact clavicle and of midshaft clavicular fractures fixed with TEN and with a reconstruction plate were built. The distal clavicle displacement, peak stress, and stress distribution on the 3 finite element models were calculated under the axial compression and cantilever bending.In both loading configurations, TEN generated the highest displacement of the distal clavicle, followed by the intact clavicle and the reconstruction plate. TEN showed higher peak bone and implant stresses, and is more likely to fail in both loading configurations compared with the reconstruction plate. TEN led to a stress distribution similar to that of the intact clavicle in both loading configurations, whereas the stress distribution with the reconstruction plate was nonphysiological in cantilever bending.TEN is generally preferable for treating simple displaced fractures of the midshaft clavicle, because it showed a stress distribution similar to the intact clavicle. However, TEN provides less stability, and excessive exercise of and weight bearing on the ipsilateral shoulder should be avoided in the early postoperative period. Fixation with a reconstruction plate was more stable but showed obvious stress shielding. Therefore, for patients with a demand for early return to activity, reconstruction plate fixation may be preferred.

The perennial O. rufipogon (common wild rice), which is considered to be the ancestor of Asian cultivated rice species, contains many useful genetic resources, including drought resistance genes. However, few studies have identified the drought resistance and tissue-specific genes in common wild rice.In this study, transcriptome sequencing libraries were constructed, including drought-treated roots (DR) and control leaves (CL) and roots (CR). Using Illumina sequencing technology, we generated 16.75 million bases of high-quality sequence data for common wild rice and conducted de novo assembly and annotation of genes without prior genome information. These reads were assembled into 119,332 unigenes with an average length of 715 bp. A total of 88,813 distinct sequences (74.42% of unigenes) significantly matched known genes in the NCBI NT database. Differentially expressed gene (DEG) analysis showed that 3617 genes were up-regulated and 4171 genes were down-regulated in the CR library compared with the CL library. Among the DEGs, 535 genes were expressed in roots but not in shoots. A similar comparison between the DR and CR libraries showed that 1393 genes were up-regulated and 315 genes were down-regulated in the DR library compared with the CR library. Finally, 37 genes that were specifically expressed in roots were screened after comparing the DEGs identified in the above-described analyses.This study provides a transcriptome sequence resource for common wild rice plants and establishes a digital gene expression profile of wild rice plants under drought conditions using the assembled transcriptome data as a reference. Several tissue-specific and drought-stress-related candidate genes were identified, representing a fully characterized transcriptome and providing a valuable resource for genetic and genomic studies in plants.

T-cell epitopes play the important role in T-cell immune response, and they are critical components in the epitope-based vaccine design. Immunogenicity is the ability to trigger an immune response. The accurate prediction of immunogenic T-cell epitopes is significant for designing useful vaccines and understanding the immune system.In this paper, we attempt to differentiate immunogenic epitopes from non-immunogenic epitopes based on their primary structures. First of all, we explore a variety of sequence-derived features, and analyze their relationship with epitope immunogenicity. To effectively utilize various features, a genetic algorithm (GA)-based ensemble method is proposed to determine the optimal feature subset and develop the high-accuracy ensemble model. In the GA optimization, a chromosome is to represent a feature subset in the search space. For each feature subset, the selected features are utilized to construct the base predictors, and an ensemble model is developed by taking the average of outputs from base predictors. The objective of GA is to search for the optimal feature subset, which leads to the ensemble model with the best cross validation AUC (area under ROC curve) on the training set.Two datasets named 'IMMA2' and 'PAAQD' are adopted as the benchmark datasets. Compared with the state-of-the-art methods POPI, POPISK, PAAQD and our previous method, the GA-based ensemble method produces much better performances, achieving the AUC score of 0.846 on IMMA2 dataset and the AUC score of 0.829 on PAAQD dataset. The statistical analysis demonstrates the performance improvements of GA-based ensemble method are statistically significant.The proposed method is a promising tool for predicting the immunogenic epitopes. The source codes and datasets are available in S1 File.

Suppressor of cytokine signaling 3 (SOCS3) plays an important role in mice fetal liver erythropoiesis, but the roles of SOCS3 in human hematopoietic stem cells (HSCs) have not been well investigated. In the present study, lentiviral small interference RNA expression vectors (shRNA) of SOCS3 were constructed and stably transferred into HSCs. We found that SOCS3 knockdown induced erythroid expansion in HSCs. Conversely, Ectopic expression of SOCS3 in progenitor cells blocked erythroid expansion and erythroid colony formation of HSCs. To further explore the involved mechanism, we compared gene expression profiles of SOCS3-shRNA tranduced HSCs with that of control HSCs by whole genome microarrays. The results indicated that cell developmental process related genes, especially hematopoietic lineage-specific genes, associated with the responses to SOCS3 in HSCs.Downexpression of SOCS3 in HSCs or differentiated erythroid progenitor cells induced a transcriptional program enriched for erythroid development relative genes. Our results proved that SOCS3 down-expression induced lineage commitment towards erythroid progenitor cell fate by activation of erythroid-specific gene in HSCs and provided new insight into the mechanism of erythropoietic development.

Currently, the clinical management of visceral pain remains unsatisfactory for many patients suffering from this disease. While preliminary animal studies have suggested the effectiveness of gabapentin in successfully treating visceral pain, the mechanism underlying its analgesic effect remains unclear. Evidence from other studies has demonstrated the involvement of protein kinase C (PKC) and extracellular signal-regulated kinase1/2 (ERK1/2) in the pathogenesis of visceral inflammatory pain. In this study, we tested the hypothesis that gabapentin produces analgesia for visceral inflammatory pain through its inhibitory effect on the PKC-ERK1/2 signaling pathway. Intracolonic injections of formalin were performed in rats to produce colitis pain. Our results showed that visceral pain behaviors in these rats decreased after intraperitoneal injection of gabapentin. These behaviors were also reduced by intrathecal injections of the PKC inhibitor, H-7, and the ERK1/2 inhibitor, PD98059. Neuronal firing of wide dynamic range neurons in L6-S1 of the rat spinal cord dorsal horn were significantly increased after intracolonic injection of formalin. This increased firing rate was inhibited by intraperitoneal injection of gabapentin and both the individual and combined intrathecal application of H-7 and PD98059. Western blot analysis also revealed that PKC membrane translocation and ERK1/2 phosphorylation increased significantly following formalin injection, confirming the recruitment of PKC and ERK1/2 during visceral inflammatory pain. These effects were also significantly reduced by intraperitoneal injection of gabapentin. Therefore, we concluded that the analgesic effect of gabapentin on visceral inflammatory pain is mediated through suppression of PKC and ERK1/2 signaling pathways. Furthermore, we found that the PKC inhibitor, H-7, significantly diminished ERK1/2 phosphorylation levels, implicating the involvement of PKC and ERK1/2 in the same signaling pathway. Thus, our results suggest a novel mechanism of gabapentin-mediated analgesia for visceral inflammatory pain through a PKC-ERK1/2 signaling pathway that may be a future therapeutic target for the treatment of visceral inflammatory pain.