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Sortase A (SrtA) is a membrane-associated enzyme that anchors surface-exposed proteins to the cell wall envelope of Gram-positive bacteria such as Staphylococcus aureus. As SrtA is essential for Gram-positive bacterial pathogenesis but dispensable for microbial growth or viability, SrtA is considered a favorable target for the enhancement of novel anti-infective drugs that aim to interfere with key bacterial virulence mechanisms, such as biofilm formation, without developing drug resistance. Here, we used virtual screening to search an in-house natural compound library and identified two natural compounds, N1287 (Skyrin) and N2576 ((4,5-dichloro-1H-pyrrol-2-yl)-[2,4-dihydroxy-3-(4-methyl-pentyl)-phenyl]-methanone) that inhibited the enzymatic activity of SrtA. These compounds also significantly reduced the growth of S. aureus but possessed moderate mammalian toxicity. Furthermore, S. aureus strains treated with these compounds exhibited reduction in adherence to host fibrinogen, as well as biofilm formation. Hence, these compounds may represent an anti-infective therapy without the side effects of antibiotics.

Most of the drugs currently prescribed for cancer treatment are riddled with substantial side effects. In order to develop more effective and specific strategies to treat cancer, it is of importance to understand the biology of drug targets, particularly the newly emerging ones. A comprehensive evaluation of these targets will benefit drug development with increased likelihood for success in clinical trials. The folate-mediated one-carbon (1C) metabolism pathway has drawn renewed attention as it is often hyperactivated in cancer and inhibition of this pathway displays promise in developing anticancer treatment with fewer side effects. Here, we systematically review individual enzymes in the 1C pathway and their compartmentalization to mitochondria and cytosol. Based on these insight, we conclude that (1) except the known 1C targets (DHFR, GART, and TYMS), MTHFD2 emerges as good drug target, especially for treating hematopoietic cancers such as CLL, AML, and T-cell lymphoma; (2) SHMT2 and MTHFD1L are potential drug targets; and (3) MTHFD2L and ALDH1L2 should not be considered as drug targets. We highlight MTHFD2 as an excellent therapeutic target and SHMT2 as a complementary target based on structural/biochemical considerations and up-to-date inhibitor development, which underscores the perspectives of their therapeutic potential.

Sortase A (SrtA) is a membrane-associated enzyme that anchors surface-exposed proteins to the cell wall envelope of Gram-positive bacteria such as Staphylococcus aureus. As SrtA is essential for Gram-positive bacterial pathogenesis but dispensable for microbial growth or viability, SrtA is considered a favorable target for the enhancement of novel anti-infective drugs that aim to interfere with key bacterial virulence mechanisms, such as biofilm formation, without developing drug resistance. Here, we used virtual screening to search an in-house natural compound library and identified two natural compounds, N1287 (Skyrin) and N2576 ((4,5-dichloro-1H-pyrrol-2-yl)-[2,4-dihydroxy-3-(4-methyl-pentyl)-phenyl]-methanone) that inhibited the enzymatic activity of SrtA. These compounds also significantly reduced the growth of S. aureus but possessed moderate mammalian toxicity. Furthermore, S. aureus strains treated with these compounds exhibited reduction in adherence to host fibrinogen, as well as biofilm formation. Hence, these compounds may represent an anti-infective therapy without the side effects of antibiotics.

To observe the impact of moxa-stick with different diameters and at different distances on skin temperature in local "Zusanli"(ST36) region, so as to select suitable specifications for moxibustion.A total of 120 male SD rats were randomly divided into diameters of 0.5, 0.9, 1.2 and 1.8 cm, and distances of 1, 2, 3, 4 and 5 cm groups, with 6 rats in each group. Moxa-stick with different diameters mentioned above was applied to the right ST36 (right hind limb) for 10 min every time at different distances (between the ignited moxa-stick tip and the skin) mentioned above, and the left ST36 was used as the control point. The skin temperature was detected by using an infrared thermometer.After application of moxibustion to ST36 region, the skin temperature was increased gradually along with the increased diameter of moxa-sticks and decreased along with the increased distance from the ignited moxa-stick tip to the skin. There were no significant changes in the skin temperature of the left control acupoint ST36. The skin temperature was below 40 ℃, between 43 to 55 ℃, over 43℃ and between 43 to 61 ℃, when the moxa-stick was 0.5 cm, 0.9 cm, 1.2 cm and 1.8 cm in diameter, and was kept 1, 2, 3 and 3 to 5 cm away from the skin surface, respectively. When the moxa-stick with a diameter of 1.8 cm was kept at a distance of 1 to 2 cm, the skin temperature reached 71 to 93 ℃ to cause obvious local burn lesion.During moxibustion, the ignited moxa-sticks with diameters of 0.5, 0.9, 1.2 and 1.8 cm are suitable to be kept less than 1, 1 to 2, 2 to 3, and 3 to 5 cm away from the skin surface of ST36, respectively.

Here Phoebe hekouensis Bing Liu, W.Y. Jin, L.N. Zhao & Y. Yang from south-eastern Yunnan Province of China is described as new to science. This species is morphologically similar to P. megacalyx H.W. Li in the twigs being robust and brownish tomentose, the ovary densely pubescent and the tepals longer than 1 cm, but differs from the latter species by the leaves being broader, up to 18 cm (vs. 4.5–11.5 cm), the inflorescences shorter, ca. 10–15 cm long (vs. up to 23 cm), the ovary completely and densely pubescent (vs. pubescent only at the apical portion) and the stigma conspicuous (vs. inconspicuous). The new species also resembles P. macrocarpa C.Y. Wu, but differs from the latter by the tepals being longer, 9–13 mm long (vs. ca. 4 mm).

Background The differential diagnoses of patients hospitalized for respiratory infections due to influenza virus vs other pathogens are challenging. Our study investigated whether hematological parameters such as neutrophil (N), lymphocyte (L), platelet (PLT), and neutrophil‐to‐lymphocyte ratio (NLR) contributed in diagnosing influenza virus infections and in discriminating other respiratory infections. Methods We retrospectively analyzed the laboratory characteristics of 307 patients with respiratory infections caused by influenza/non‐influenza virus and bacteria. The diagnostic abilities of hematological indexes were evaluated in the patients compared with 100 healthy people. Results The hematological parameters in patients with influenza virus infection were dramatically altered compared with those in the controls. Additionally, among the systemic inflammatory markers, the sensitivity of NLR for influenza detection was higher than that of N and L. PLT was significantly lower in influenza virus‐positive infection than in influenza virus‐negative infection. Moreover, when patients with influenza virus infection were cured, PLT returned to a normal level. The red blood cell (RBC) and hemoglobin (Hb) levels of influenza virus infection were higher than those of bacterial infection. Compared with traditional N and L, NLR and platelet‐to‐neutrophil (PNR) showed greater significance between influenza virus and bacterial infection (P

Daqu provides a complex and unique microbial ecosystem and acts as a fermentation starter and a source of flavor compounds for Chinese strong-flavor Baijiu production. Dynamic changes in Daqu bacterial composition and physicochemical properties during production were studied using physicochemical analysis and Illumina HiSeq sequencing, revealing that the bacterial α- and β-diversity changed markedly after the start of fermentation. The dominant bacterial genera were Cyanobacteria, Proteobacteria and Firmicutes; Enterobacter, within Proteobacteria, was at the most influential node of the interaction network, and was positively correlated with Bacillus, Pantoea and Pedicoccus. Redundancy analysis showed that the bacterial community structure was closely related to the physicochemical properties of Daqu, especially the acidity, cellulase activity and moisture. These findings clarified the complex bacterial community succession and interactions between organisms and with physicochemical properties, during Daqu fermentation, thereby enabling quality improvement of strong-flavor Baijiu, by augmenting selected bacterial cultures, or by controlling environmental factors.

BACKGROUND: Septic cardiomyopathy (SCM) occurs in the early stage of sepsis and septic shock, which has implications for treatment strategies and prognosis. Additionally, myocardial involvement in the early stages of sepsis is difficult to identify. Here, we assess subclinical myocardial function using laboratory tests and speckle-tracking echocardiography (STE). METHODS: Emergency department patients diagnosed with sepsis or septic shock were included for analysis. Those with other causes of acute or pre-existing cardiac dysfunction were excluded. Transthoracic echocardiography (TTE), including conventional echocardiography and STE, were performed for all patients three hours after initial resuscitation. Samples for laboratory tests were taken around the time of TTE. RESULTS: Left ventricular functions of 60 patients were analyzed, including 21 septic shock patients and 39 sepsis patients. There was no significant difference in global longitudinal strain (GLS), global circumferential strain (GCS), or global radical strain (GRS) between patients with sepsis and septic shock (all with P>0.05). However, GLS and GCS were significantly less negative in patients with abnormal troponin levels or in patients with abnormal left ventricular ejection fraction (LVEF) values (all with P

Objective A retrospective observational cohort study was conducted to evaluate the efficacy and safety of tacrolimus in Osserman grade III and Osserman grade IV myasthenia gravis (MG) patients. Patients and methods MG patients admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine between June 2011 and January 2017 with grade III and grade IV according to the modified Osserman scale were recruited and received a telephone follow-up in September 2017. Patients treated with tacrolimus plus prednisone were compared with those treated without tacrolimus. The efficacy of tacrolimus was assessed using MG-activities of daily living (MG-ADL) score, Osserman classification, Myasthenia Gravis Foundation of America (MGFA) post intervention status (PIS), the number of hospitalizations, the number of myasthenic crises and deaths. The adverse drug effects of tacrolimus were monitored. Results A total of 124 patients were included. The tacrolimus group had a significantly lower MG-ADL score than the control group at follow-up (1.90 ± 2.27vs 2.97 ± 2.78, p = 0.029). The difference of MG-ADL score between baseline and after follow-up was significantly greater in the tacrolimus group than the control group (-7.20 ± 2.95 vs -5.52 ± 2.91, p = 0.003). Fewer patients were hospitalized in the tacrolimus group (p = 0.011). The Osserman classification, MGFA PIS, the number of myasthenic crises and deaths did not differ significantly between the two groups. Nineteen patients in the tacrolimus group had adverse drug reactions, but no severe adverse effects appeared. Conclusion Our study suggested that tacrolimus could be an effective and safe treatment for Osserman grade III and Osserman grade IV MG patients.

Corynebacterium pyruviciproducens (C. pyruviciproducens, CP), as a newly discovered immunomodulator, has been confirmed to have a stronger immunoregulation than Propionibacterium acnes (P. acnes) of the traditional immune adjuvant, by previous experiments with model antigen ovalbumin and sheep red blood cells. Here, it was designed to assess its ability to resist methicillin-resistant Staphylococcus aureus (MRSA), since MRSA as a vital gram positive pathogen is characterized by high morbidity and mortality. In this report, it was indicated that C. pyruviciproducens and its peptidoglycan (CP-PGN) could help to be against bloodstream infection of MRSA with raised survival rate, decreased bacteria load and alleviated systemic inflammation, and these effects of CP-PGN were more pronounced. However, the whole CP was inclined to prevent localized abdominal infection of MRSA from progressing to a systemic infection. And they showed the potential as a therapeutic drug alone or combined with vancomycin. The diversity of capacity of activating macrophages induced by CP and CP-PGN may result in distinct resistance to MRSA in different infection models. Furthermore, both CP and CP-PGN induced M1 macrophages. In conclusion, CP and its PGN could act as promising immune agents to treat and prevent MRSA infection.

Although several optimal mycobacterial interspersed repetitive units–variable number tandem repeat (MIRU–VNTR) loci have been suggested for genotyping homogenous Mycobacterium tuberculosis, including the Beijing genotype, a more efficient and convenient selection strategy for identifying optimal VNTR loci is needed. Here 281 M. tuberculosis isolates were analyzed. Beijing genotype and non-Beijing genotypes were identified, as well as Beijing sublineages, according to single nucleotide polymorphisms. A total of 22 MIRU–VNTR loci were used for genotyping. To efficiently select optimal MIRU–VNTR loci, we established accumulations of percentage differences (APDs) between the strains among the different genotypes. In addition, we constructed a minimum spanning tree for clustering analysis of the VNTR profiles. Our findings showed that eight MIRU–VNTR loci displayed disparities in h values of ≥0.2 between the Beijing genotype and non-Beijing genotype isolates. To efficiently discriminate Beijing and non-Beijing genotypes, an optimal VNTR set was established by adding loci with APDs ranging from 87.2% to 58.8%, resulting in the construction of a nine-locus set. We also found that QUB11a is a powerful locus for separating ST10s (including ST10, STF and STCH1) and ST22s (including ST22 and ST8) strains, whereas a combination of QUB11a, QUB4156, QUB18, Mtub21 and QUB26 could efficiently discriminate Beijing sublineages. Our findings suggested that two nine-locus sets were not only efficient for distinguishing the Beijing genotype from non-Beijing genotype strains, but were also suitable for sublineage genotyping with different discriminatory powers. These results indicate that APD represents a quantitative and efficient approach for selecting MIRU–VNTR loci to discriminate between divergent M. tuberculosis sublineages.

Robust recovery of multiple subspace structures from high-dimensional data with noise has received considerable attention in computer vision and pattern recognition. Low-Rank Representation (LRR) as a typical method has made satisfactory results in subspace clustering. Latent Low-Rank Representation (LLRR) is an advanced version of LRR, which considers the row and column of data to solve the insufficient samples problem. However, they fail to exploit the local structures of data. To address this problem, Latent Sparse Low-Rank Representation (LSLRR) is proposed to capture the local and global structures of data by considering sparse and low-rank constraints simultaneously. In this way, LSLRR not only solves the clustering problem, but also extracts significant features for classification. Inexact Augmented Lagrange Multiplier method (IALM) is utilized to solve its objective function. Experimental results in subspace clustering and salient features extraction demonstrate the proposed LSLRR have a favorable performance.

Hematopoietic stem cells (HSCs) aging is associated with hematopoietic dysfunction and diseases. Our previous study showed that lead exposure induced a functional decline in HSCs. Allicin, a chemical extracted from the garlic (Allium sativum L.), has been reported to have antioxidative and anti-inflammatory effects. However, the biological activities of allicin on lead-induced toxicity, especially in the hematopoietic system, remain unclear. Here, we found that lead exposure elicited aging phenotypes in HSCs, including perturbed cell quiescence, disabled self-renewal function and colony-forming ability, and myeloid-biased differentiation, all of which contributed to significant hematopoietic disorders in mice. Intragastric administration of allicin substantially ameliorated lead-induced HSCs aging phenotypes in vivo. Lead exposure induced a peroxide condition in HSCs leading to DNA damage, which reduced expression of the glycolytic enzyme pyruvate kinase M2 isoform (PKM2), a phenotype which was significantly ameliorated by allicin treatment. These findings suggested that allicin alleviated lead-induced HSCs aging by up-regulating PKM2 expression; thus, it could be a natural herb for preventing lead toxicity.

Understanding the reaction mechanism of CRISPR-associated protein 9 (Cas9) is crucial for the application of programmable gene editing. Despite the availability of the structures of Cas9 in apo- and substrate-bound forms, the catalytically active structure is still unclear. Our first attempt to explore the catalytic mechanism of Cas9 HNH domain has been based on the reasonable assumption that we are dealing with the same mechanism as endonuclease VII, including the assumption that the catalytic water is in the first shell of the Mg2+ . Trying this mechanism with the cryo-EM structure forced us to induce significant structural change driven by the movement of K848 (or other positively charged residue) close to the active site to facilitate the proton transfer step. In the present study, we explore a second reaction mechanism where the catalytic water is in the second shell of the Mg2+ and assume that the cryo-EM structure by itself is a suitable representation of a catalytic-ready structure. The alternative mechanism indicates that if the active water is from the second shell, then the calculated reaction barrier is lower compared with the corresponding barrier when the water comes from the first shell.

Elucidating the nature of the gene editing mechanism of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is an important task in view of the role of this breakthrough to the advancement of human medicine. In particular, it is crucial to understand the catalytic mechanism of Cas9 (one of the CRISPR associated proteins) and its role in confirming accurate editing. Thus, we focus in this work on an attempt to analyze the catalytic mechanism of Cas9. Considering the absence of detailed structural information on the active form of Cas9, we use an empirical valence bond (EVB) which is calibrated on the closely related mechanism of T4 endonuclease VII. The calibrated EVB is then used in studying the reaction of Cas9, while trying several structural models. It is found that the catalytic activation requires a large conformational change, where K848 or other positively charged group moves from a relatively large distance toward the scissile phosphate. This conformational change leads to the change in position of the Mg(2+) ion and to a major reduction in the activation barrier for the catalytic reaction. Our finding provides an important clue on the nature of the catalytic activation of CAS9 and thus should help in elucidating a key aspect of the gene editing process. For example, the approach used here should be effective in exploring the nature of off target activation and its relationship to the energetics of the unwinding process. This strategy may offer ways to improve the selectivity of Cas9.

High temperature directly affects the yield and quality of crops. Plant Hsfs play vital roles in plant response to heat shock. In the present study, ZmHsf05 was isolated from maize (Zea mays L.) using homologous cloning methods. The sequencing analysis demonstrated that CDS of ZmHsf05 was 1080 bp length and encoded a protein containing 359 amino acids. The putative amino acid sequence of ZmHsf05 contained typical Hsf domains, such as DBD, OD, NLS and AHA motif. Subcellular localization assays displayed that the ZmHsf05 is localized to the nucleus. ZmHsf05 was expressed in many maize tissues and its expression level was increased by heat stress treatment. ZmHsf05 rescued the reduced thermotolerance of the athsfa2 mutant in Arabidopsis seedlings. Arabidopsis seedlings of ZmHsf05-overexpressing increased both the basal and acquired thermotolerances. After heat stress, the ZmHsf05-overexpressing lines showed enhanced survival rate and chlorophyll content compared with WT seedlings. The expression of Hsps was up-regulated in the ZmHsf05-overexpressing Arabidopsis lines after heat stress treatment. These results suggested that ZmHsf05 plays an important role in both basal and acquired thermotolerance in plants.

In the present study, effects of floroquinone on anaplastic thyroid cancer cell lines and mouse tumor xenografts were investigated. Increase in the concentration of floroquinone from 10 to 100 µM reduced the cell growth from 98 to 17% after 48 hours in HOTHC cells. Similarly, in FRO cells growth rate was found to be 96 and 21%, respectively at 10 and 100 µM concentra-tions of floroquinone. Western blot analysis showed a marked reduction in Bcl-2 expression and increased in Bax, caspase-3 and cleaved PARP expre-ssion in HOTHC cell lines on treatment with floroquinone. Floroquinone treatment of the HOTHC cells led to inhibition of the cobalt chloride-induced increase in the hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor expression. In HOTHC cells, floroquinone treatment inhibited the tube formation and migration potential significantly compared to control cells. Treatment of the mouse bearing HOTHC tumor xenograft with 50 and 100 mg/kg doses of floroquinone alternatively for one month reduced the tumor volume to 48 and 17%, respectively compared to the control. Thus, floroquinone effectively inhibits growth of thyroid cancer and can be used for its treatment.Video Clip:Migration assay: 1 min 09 sec

Background: This article will evaluate the effects of traditional Chinese medicine (TCM) combined with chemotherapy on the immune function and quality of life of patients with non-small cell lung cancer (NSCLC), and evaluate the published side effects. Methods: The systematic review and meta-analysis will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The databases we will search include: PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biomedicine, Wan fang Data, and Technology Periodical Database. The search date is from inception to June 30, 2020. There are no restrictions on the document language. The literatures included in this study are randomized controlled trials. The main results include ratio of CD3+, CD4+, CD8+, CD4+/CD8+, NK cells, the level of IgA, IgG, IgM, and Karnofsky performance status score. The secondary result is to evaluate various side effects during treatment. We will use the Cochrane Collaboration tool to evaluate each study and use Review Manager software (RevMan, version 5.3) to merge and analyze the data. The 2 researchers will independently cross-screen the literature, extract data, and evaluate the quality. If there are differences, we will resolve them through discussion or consultation with a third reviewer. Results: The results of this study will provide high-quality evidence for the effect of TCM combined with chemotherapy on the immune function and quality of life of patients with NSCLC. Conclusion: This article will comprehensively evaluate the effects of TCM combined with chemotherapy on the immune function and quality of life of patients with NSCLC, and provide evidence-based evidence for clinical practice. Ethics: Since the data used in this study is based on previous trials and does not involve patient privacy, ethical approval is not required. Study registration number: INPLASY202070071

Supplemental Digital Content is available in the text, Background: The main component of cinobufacini injection is dry toad skin, which is used as adjuvant therapy for stage III/IV non-small cell lung cancer patients in long-term combination with vinorelbine and cisplatin. However, the efficacy and safety of this combination therapy remain unclear. Methods: A systematic review and meta-analysis will be conducted following the preferred reported items for systematic review and meta-analysis guidelines. Two independent reviewers (LRL and ZLN) will carry out a comprehensive search of the PubMed, Web of Science, Cochrane Library, EMBASE, the Chinese Science and Technology Periodical Database, China National Knowledge Infrastructure, Wanfang Databases, China Biology Medicine. The last search date will be July 30, 2020. Reference list of all selected articles will independently screened to identify additional studies left out in the initial search. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias of the randomized controlled trials. Outcome index: The main efficacy indicators were based on the objective efficacy evaluation criteria of the World Health Organization antineoplastic drugs or the objective efficacy evaluation criteria of solid tumors established by RECIST. Secondary criteria Karnofsky performance scale (KPS) score, pain efficacy criteria, side effects of chemotherapy such as myelosuppression and gastrointestinal symptoms. Assessment of risk of bias and data synthesis will be conducted using Review Manager V5.3 software. Results: This study will systematically evaluate the efficacy and safety of cinobufacini combined with vinorelbine and cisplatin in the treatment of stage III/IV non-small cell lung cancer. The results of this systematic review will be published in peer-reviewed scientific journals. Ethics: The ethical approval is not required since systematic review is based on published studies. INPLASY registration number: INPLASY202060091.

In this work, we present a generalizable directed computational evolution protocol to effectively reduce the sequence space to be explored in rational enzyme design. The protocol involves in silico mutation modeling and substrate docking to rapidly identify mutagenesis hotspots that may enhance an enzyme's substrate binding and overall catalysis. By applying this protocol to a quorum-quenching Geobacillus kaustophilus lactonase, GKL, we generated 1,881 single mutants and docked high-energy intermediates of nine acyl homoserine lactones onto them. We found that Phe28 and Tyr99 were two hotspots that produced most of the predicted top 20 mutants. Of the 180 enzyme-substrate combinations (top 20 mutants × 9 substrates), 51 (28%) exhibited enhanced substrate binding and 22 (12%) had better overall activity when compared with wild-type GKL. X-ray crystallographic studies of Y99C and Y99P provided rationalized explanations for the enhancement in enzyme function and corroborated the utility of the protocol.

Salvia miltiorrhiza is one of the 40 most commonly used traditional Chinese medicinal materials in clinics. It is effective in activating blood circulation, removing blood stasis, relieving pain through the meridian, clearing the heart and removing irritations, and cooling blood and eliminating blemishes. Each main production area has developed a unique production method and processing technology, in accordance with local conditions. The processed products included in Chinese Pharmacopoeia are purified and wine-fried S. miltiorrhiza. In addition, the Chinese province's standards include the vinegar-fried and wine-fried types. S. miltiorrhiza is produced in more areas and is more extensively processed, with large variations in specifications. The challenge in establishing a uniform quality standard affects the clinical application of decoction pieces. This review has explored the books of the past dynasties, summarized the relevant literature published in the past three decades, discussed the processing methods of S. miltiorrhiza, and provided a basis for further research on the processing method of the original sample. In particular, we integrate fresh cut processing as the starting point for in-depth research, discuss the processing technology specifications, and formulate quality product standards.

The Chinese oak silkworm, Antheraea pernyi, is an important alternate host for mass production of Trichogramma parasitoids, which play a vital role in the biological control of lepidopterous pests in China. The quality of A. pernyi eggs is particularly important for mass production of these parasitoids. In this study, a pathogenic bacterium, isolated and purified from A. pernyi eggs that had turned gray in color, was identified as Serratia marcescens. We used morphology, biochemistry and 16S rDNA analysis to characterize the strain, which was named “APE strain”. Serratia marcescens APE strain was determined to be the causal bacterium associated with the disease in the eggs, verified by a test based on Koch’s Postulates. We tested the pathogenicity of S. marcescens APE strain on A. pernyi eggs; the percentage of diseased (gray) eggs reached 57.78% when uninfected eggs were exposed to a concentration of 1 × 109 cfu/mL bacterial suspension for 7 h. S. marcescens was transmitted mechanically by Trichogramma parasitoids. The transmission rate was 25.56%. In a horizontal transmission test, the highest percentage of uninfected eggs that developed infections was 51.43% after being treated with contents of diseased eggs for 12 h. In a vertical transmission test, the number of infected eggs per treated adult female was 63.8–92.3 after treatment with different S. marcescens concentrations, significantly lower than the 304.3 eggs per female in the control group. Furthermore, the percentage of infected (gray) eggs produced by adult moths exposed to bacteria in the larval stage was 80.5–85.3%.

The association of the degree of aging based on the whole-brain anatomical characteristics, or brain age, with smoking, alcohol consumption, and individual genetic variants is unclear. Here, we investigated these associations through analyzing data collected for UK Biobank subjects with an age range of 45 to 79 years old. We first trained a statistical model for obtaining relative brain age (RBA), a metric describing a subject’s brain age relative to peers, based on a randomly selected training set subjects (n=2,679). We then applied this model to the evaluation set subjects (n=6,252) and further tested the association of RBA with tobacco smoking, alcohol consumption, and 529,098 genetic variants. We found that daily or almost daily consumption of smoking or alcohol was significantly associated with increased RBA (P

DNA mismatch repair was proposed to play a pivotal role in the development and prognosis of colorectal cancer. However, the prognostic value of mismatch repair on colorectal cancer is still unknown. The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched. The articles about mismatch repair (including hMLH1, hMSH2, hMSH3, hMSH6, hPMSH1, and hPMSH2) deficiency for the prognosis of patients with colorectal cancer were included in the study. The hazard ratio and its 95% confidence interval were used to measure the impact of mismatch repair deficiency on survival time. Twenty-one articles were included. The combined hazard ratio for mismatch repair deficiency on overall survival was 0.59 (95% confidence interval: 0.50-0.69) and that on disease-free survival was 0.57 (95% confidence interval: 0.43-0.75). In subgroup analysis, there were a significant association between overall survival and mismatch repair deficiency in Asian studies (hazard ratio: 0.67; 95% confidence interval: 0.50-0.91) and Western studies (hazard ratio: 0.56; 95% confidence interval: 0.46-0.67). For disease-free survival, the hazard ratios in Asian studies and Western studies were 0.55 (95% confidence interval: 0.38-0.81) and 0.62 (95% confidence interval: 0.50-0.78), respectively. Our meta-analysis indicated that mismatch repair could be used to evaluate the prognosis of patients with colorectal cancer.

Ten compounds were isolated from the methanol extract of Zanthoxylum nitidum through silica gel, Sephadex LH-20, RP-18 and HPLC chromatography techniques. Their structures were elucidated by the MS and NMR spectra as zanthonitidine B(1), cyclo-(Leu-Leu-Leu-Leu-Ile)(2),6S-10-O-demethylbocconoline(3), liriodenine(4), isoplatydesmine(5), 5, 5'-dimethoxylariciresinol(6), syringaresinol (7), episyringaresinol (8), marmesin (9) and syringaldehyde (10). Among them,1 is a new alkaloid,2 is a cyclopentapeptide isolated from plant kingdom for the first time, and 3 is from the genus Zanthoxylum for the first time. Compounds 3 and 4 exhibited cytoxoxicity against three human cancer cell lines HT29, A549 and MDA-MB-231 with IC₅₈ values of 27.37, 24.10, 33.58 μmol·L⁻¹ and 9.12,6.05, 11.35 μmol·L⁻¹, respectively.

Nineteen compounds, including kihadanin D (1), obacunone (2), kihadanin A (3), kihadanin B (4), kihadanin C (5), limonin (6), evodol (7), fraxinellone (8), furo[2,3-b]quinolin-4-ol (9), preskimmianine (10), ifflaiamine (11), dictamnol (12), naringenin (13), diosmetin (14), wogonin (15), scopoletin (16), cleomiscosin A (17), apocynin (18), and methyl pyroglutamate (19), were isolated from the methanol extract of the root barks of Dictamnus dasycarpus by using various column chromatographies. Their chemical structures were extensively determined on basis of UV, IR, NMR, MS, and CD spectroscopic data analyses. Among them, 1 is a new limonoid, 9 was isolated from plant kingdom for the first time, 11, 13-14 and 17-19 were obtained from the genus Dictamnnus for the first time. Cytotoxicities of compounds 1-18 were tested, and the results indicated that 1 exhibited cytotoxicities against three human cancer cell lines MDA-MB-231, A549 and HT29 with IC₅₈ values of 16.22, 21.72 and 31.06 μmol·L⁻¹, respectively.

Radioresistance is an important obstacle to nasopharyngeal carcinoma (NPC) therapy. In this study, we explored the role of RNA-binding motif protein 3 (RBM3) in the radioresistance of NPC and its underlying mechanism. We measured the expression of RBM3 in 20 clinical NPC tissues and in NPC cell lines. We found that RBM3 was upregulated in radioresistant NPC tissues and cells. Radioresistant NPC cells (CNE1/IR) and parental NPC cells (CNE1) were subjected to RBM3-shRNA knockdown and RBM3 overexpression, respectively. RBM3 depletion in CNE1/IR cells sensitized cells to radiotherapy, increased DNA damage, and accelerated the rate of apoptosis. In contrast, RBM3 overexpression in CNE1 cells significantly enhanced radioresistance and reduced the rate of apoptosis. Additionally, radioresistance conferred by RBM3 was attributed to the activation of the AKT/Bcl-2 signaling pathway and reduction of caspase 3. Inhibition of AKT signaling attenuated RBM3-mediated radioresistance. Furthermore, RBM3 directly interacted with PI3K subunit p85 in NPC cell lines. Altogether, our data demonstrate that RBM3 enhances radioresistance by inhibiting the apoptotic response to radiotherapy through the PI3K/AKT/Bcl-2 signaling pathway. RBM3 may serve as a novel factor for predicting radioresistance and as a molecular target in the treatment of NPC.

With the rapid development of e-commerce, the online product reviews and ratings play an important role on the purchase decisions of consumers. Most of the previous researches on online product reviews had focused on the empirical results, however, use of intuition usually resulted in poorer decisions and a lack of the scientific results is difficult to obtain the same conclusions. This study designed a new review ranking system which is used to examine how consumers read the online product review. All the online product reviews were collected from consumers through this system. After summarized and analyzed these data, the results demonstrated that most of consumers first searched out and read positive reviews, but spent more time on the negative comments. In addition, compared with positive reviews, consumers felt they need to read negative reviews even more carefully before they fully trusted a business. Thus, the negative reviews influence the purchase decisions of online shoppers since they would pay most attention to the negative reviews. This study can help enterprises to understand the consumers’ perspective on using the online product reviews and give new insight for future research as well as effectively assist in their management on online reviews.

Translational biomedical research is generating exponentially more data: thousands of whole-genome sequences (WGS) are now available; brain data are doubling every two years. Analyses of Big Data, including imaging, genomic, phenotypic, and clinical data, present qualitatively new challenges as well as opportunities. Among the challenges is a proliferation in ways analyses can fail, due largely to the increasing length and complexity of processing pipelines. Anomalies in input data, runtime resource exhaustion or node failure in a distributed computation can all cause pipeline hiccups that are not necessarily obvious in the output. Flaws that can taint results may persist undetected in complex pipelines, a danger amplified by the fact that research is often concurrent with the development of the software on which it depends. On the positive side, the huge sample sizes increase statistical power, which in turn can shed new insight and motivate innovative analytic approaches. We have developed a framework for Big Data Quality Control (BDQC) including an extensible set of heuristic and statistical analyses that identify deviations in data without regard to its meaning (domain-blind analyses). BDQC takes advantage of large sample sizes to classify the samples, estimate distributions and identify outliers. Such outliers may be symptoms of technology failure (e.g., truncated output of one step of a pipeline for a single genome) or may reveal unsuspected “ signal” in the data (e.g., evidence of aneuploidy in a genome). We have applied the framework to validate real-world WGS analysis pipelines. BDQC successfully identified data outliers representing various failure classes, including genome analyses missing a whole chromosome or part thereof, hidden among thousands of intermediary output files. These failures could then be resolved by reanalyzing the affected samples. BDQC both identified hidden flaws as well as yielded new insights into the data. BDQC is designed to complement quality software development practices. There are multiple benefits from the application of BDQC at all pipeline stages. By verifying input correctness, it can help avoid expensive computations on flawed data. Analysis of intermediary and final results facilitates recovery from aberrant termination of processes. All these computationally inexpensive verifications reduce cryptic analytical artifacts that could seriously preclude clinical-grade genome interpretation. BDQC is available at https://github.com/ini-bdds/bdqc.

The brittleness and fracture behaviors of the sintered and the two-stage aged Dy-doped NdFeB magnets were studied by a unique method of acoustic emission testing and Vickers hardness indentation method in this paper. A detailed analysis on the crack propagation mechanism along the grain boundary of the main grain phase (Nd, Dy)2Fe14B was done. By comparing the acoustic emission energy count value (E n) with the Vickers hardness indentation load (P), it is shown that there is a linear relationship between E n and P for both the sintered and the two-stage aged Dy-doped NdFeB magnets. According to the slope of E n versus P linear lines, it can be found that the two-stage aged Dy-doped NdFeB magnet is more brittle than the sintered one. It is due to that the Nd-rich grain boundary phase of the two-stage aged Dy-doped NdFeB magnet is formed as thin film and uniformly distributes around the main grain phase, which plays a significant role in increasing the intrinsic coercive force of the magnet, but decreasing its interface binding strength. Therefore, the resistance of crack propagation along the grain boundary decreases and the brittleness increases.

Treatments for pancreatic injuries have been significantly improved recently, but full recovery of pancreatic function remains difficult. Embryonic stem cells have great potentialities for self-renewal and multiple differentiations. In this study, we explored an approach to induce the differentiation of pancreatic progenitor cells from embryonic stem cells in vitro. Male mouse embryonic stem cells were cultured by the hanging-drop method to form embryoid bodies. The definitive endoderm marked by CXCR4 in embryoid bodies was sorted by magnetic activated cell sorting and subsequently administrated with b-FGF, exendin-4, and cyclopamine to induce the differentiation of putative pancreatic progenitor cells, which was monitored by Pdx1, and Shh expressions. The putative pancreatic progenitor cells were transplanted into female BALB/c mice with pancreatitis induced by L-Arginine. Male donor cells were located by detecting sex-determining region of Y-chromosome DNA. Definitive endoderm cells (CXCR4(+) cells) were sorted from 5-day embryoid bodies. After 3-day administration with b-FGF, exendin-4, and cyclopamine, Pdx1-high/Shh-low cells were differentiated from CXCR4(+) cells. These cells developed into more amylase-secreted cells in vitro and could specifically reside in the damaged pancreas acinar area in mice with acute pancreatitis to enhance the regeneration. The putative pancreatic progenitor cells (Pdx1-high/Shh-low cells) derived from mouse embryonic stem cells through the administration of b-FGF, exendin-4, and cyclopamine on the CXCR4(+) cells in vitro could improve the regeneration of injured pancreatic acini in vivo.

Summary A polyphenol oxidase (PPO) from lotus seed was purified by the procedures including ammonium sulphate precipitation and affinity chromatography. The apparent molecular mass was 38.6 kDa by SDS-PAGE. Kinetic studies showed that the Km and Vmax values for catechol were 6.04 mm and 416.67 U, respectively. The PPO performed optimal activity in 20 °C and pH 7.0. The enzymatic activity could be mainly maintained up to 50 °C and pH 4.0–7.0. The activity could be inhibited by various inhibitors including thiourea, urea, sodium hydrogen sulphite, EDTA·2Na, SDS, citric acid, guanidine hydrochloride, ascorbic acid, sodium sulphite and sodium thiosulphate. The metal ions Ba2+, Mg2+, Ca2+, Mn2+, Co2+ and Zn2+ could inhibit the activity of PPO, while Cu2+ performed obvious enhancement. The enzymatic properties of PPO could probably provide practical application in inhibiting the PPO activity and preventing enzymatic browning in the process of picking, transportation, processing and storage of fresh lotus seeds.

Background Autoimmune pancreatitis (AIP) is a distinct type of pancreatitis associated with a presumed autoimmune mechanism. The aim of this study was to analyze the clinical features and expressions of forkhead box P3 (Foxp3) and interleukin-17 (IL-17) in type 1 AIP in China and to identify factors for differentiation of AIP from non-AIP chronic pancreatitis (CP). Material/Methods We retrospectively reviewed pancreatic specimens with diagnosis of type 1 AIP and non-AIP CP at Sun Yat-Sen Memorial Hospital in China from January 2000 to December 2013. The clinical symptoms, serological data, imaging findings, histopathology, and immunohistochemical findings of Foxp3 and IL-17 in the 2 groups were analyzed. Results Twenty-nine patients with type 1 AIP and 20 patients with non-AIP CP were enrolled. Obstructive jaundice was more common in type 1 AIP than in non-AIP CP (62.1% vs. 30.0%, P=0.042). The diffuse or segmental enlargement of the pancreas was more frequent in type 1 AIP than in non-AIP CP (72.4% vs. 40.0%, P=0.038). Histopathology of type 1 AIP presented dense lymphoplasmacytic infiltration, “snowstorm-like” fibrosis and abundant immunoglobulin (Ig) G4+ cells. Foxp3+ cells were more frequently observed in type 1 AIP than in non-AIP CP. IL-17+ cell infiltration was similar between the 2 groups. Furthermore, a positive correlation was found between Foxp3+ and IgG4+ cell counts in the pancreas of patients with type 1 AIP. Conclusions Type 1 AIP has distinctive symptoms, image, and pathological characteristics, which could be used for differentiation from non-AIP CP. Foxp3+ cells might be helpful to distinguish type 1 AIP from non-AIP CP.

With the emergence of large-scale and high-performance modern production system, how to effectively improve the safety performance of the control system has become an urgent problem to be solved.[1] Fault detection and diagnosis as the main means to improve the reliability of the control system have been widely valued. Fault diagnosis is a technique to use the information in the system to detect the faults in time and take corresponding measures to ensure the safety and reliability of the system. In view of the nonlinear systems containing uncertainties, this paper combined with state observer, adaptive control, fuzzy logic, neural network and genetic algorithm are investigated in theory, such as nonlinear system fault diagnosis scheme based on observer. The main research is as follows: Firstly, the research status of fault diagnosis technology is introduced, the main method of fault diagnosis is analyzed systematically, and the fault diagnosis technology based on observer is expounded. Then, the intelligent algorithm is introduced into the control system fault diagnosis, and the fault diagnosis method based on adaptive fuzzy observer is proposed. Finally, the design and performance of the fault diagnosis scheme are verified by a numerical example. The simulation results show that the method is effective for fault diagnosis of nonlinear systems with uncertain factors.

In this paper, we study the fault tolerant control problem of actuator fault by indirect adaptive method. There are normal conditions, the failure of executor partial, interruption, and non-parametric failures of actuator form. We assume that the efficiency factor of actuator is unknown, furthermore, the external disturbances and the boundary of time-varying card failures are also unknown. In addition, compensate the actuator failure and external disturbance by designing the adaptive controller. The asymptotically stable of adaptive closed-loop system can be guaranteed whether under normal operation or under the influence of fault and disturbance based on the Lyapounov theory. And the method is proved to be effective by the simulation example.

Background Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) affecting millions of people worldwide. miR-155 has been reported to be upregulated in various inflammatory diseases and is a positive regulator of the T-cell response. IL-17 secreting helper T (Th17) cells have been heavily implicated in tissue-specific immune pathology, including UC. Methods and results Therefore, we targeted miR-155 and investigated its expression levels in a DSS-induced UC mouse model, revealing increased expression. Est-1 expression was found to have decreased, but the levels of IL-23/17/6 were raised significantly and Th17 had experienced an obvious increase. We overexpressed miR-155 using a lentiviral treatment. Increased miR-155 expression induced a more severe damage to colon tissues. In this case, the level of Est-1 decreased even further, thereby enhancing IL-23/17/6-mediated Th17 differentiation. Conclusion miR-155 seems to target Est-1 and induces UC via the IL-23/17/6-mediated Th17 pathway.

Stewart platform is a parallel linkage, which is widely used in the area of parallel robotics. Generalized Stewart Platform (GSP) consists of two rigid bodies connected with six constraints between six pairs of geometric primitives in the base and the moving platform respectively. Direct kinematics to GSP is to determine the pose of moving platform according to six constraints between the base and the moving platform. Strategies on direct kinematics to GSP were presented, which were based on graph theory and symbolic computation method. A GSP can be decomposed into smaller ones if possible, and the corresponding parameters conditions of real solutions to direct kinematics to the GSP can be obtained according to these strategies.

Medicinal plants have been used in many countries for thousands of years. For a long time, scientists have done a lot of work in order to make a study on the effective components of traditional herbal medicines (THM) and make quality control for them. Because the components of herbal medicines are various and uncertain, we need to develop standardized methods to test related items, which can estimate the source, category, authenticity, and main components of them to ensure their safety and efficacy. This article aims to introduce some of the analysis methods and quality control aspects of THM of the relevant research reports, including the identification of plants, the determination of the active ingredients or toxic components and analysis of heavy metals, pesticide residues, adulterants and counterfeits distinguishment, and identification. Among them, the fingerprint is the core of THM standardization. And the standardization is confronted with huge challenges, that everyone can do a favor.

Against the problem that the existing MPPT control algorithms of PV array have difficulties to balance both of the control accuracy and searching speed, this article presents a golden ratio optimal gradient MPPT algorithm based on the traditional optimal gradient MPPT control algorithm. The algorithm is an optimal gradient control algorithm of variable step size, it has an advantage over the traditional fixed step optimal gradient algorithms on tracking the maximum power point. The experimental results show its superiority in the searching speed and control accuracy by modeling and simulation on PSCAD.

There are many kinds of mobile power supply, in this paper, aiming at the existing mobile power cannot be automatically continued charging problem, an automatic charging and discharging circuit design, and put forward the improvement circuit corresponding to the common lithium battery over-voltage and over-current protection, battery monitoring problem. The widespread use of application of STC15W401AS, SX2105, DS2762 chip as the core device, with the corresponding peripheral circuit, provides a reference for the application of charge power supply protection circuit of lithium ion batteries based on SCM system.

β-Catenin accumulation promotes proliferation. However, the correlation between proliferation of colorectal epithelium and β-catenin in type 2 diabetes mellitus (DM) patients remains unclear.Colorectal epithelium samples from distal ends of colorectal adenocarcinomas without histological aberrances were divided into two groups: DM patients with type 2 DM for more than 1year (n=27) and non-DM patients without hyperglycemia (n=20). Samples from patients without colorectal epithelial disease or hyperglycemia served as a control group (n=6). Proliferative index was calculated as the percentage of proliferating cell nuclear antigen positive cells. Wnt/β-catenin signaling was assessed immunohistochemically and phosphorylation of β-catenin was assessed by immunofluorescence.Compared with the non-DM or control group, the proliferative index and expression of lactate dehydrogenase A and Wnt/β-catenin signaling were significantly higher in the DM group (all p0.01). The proliferative index correlated positively with β-catenin expression (Spearman correlation coefficient=0.55; p0.01). Reduced phosphorylation at serine 33/37 and increased phosphorylation at serine 675 of β-catenin were detected in the DM group (all p0.01).Enhanced proliferation, accompanied by increased aerobic glycolysis, was detected in colorectal epithelium of patients with diabetes. β-Catenin accumulation with altered phosphorylation correlated with the proliferative changes.

In order to increase the intrinsic coercivity of the Nd-Fe-B magnets, the aging process optimization had been carried out. The results showed that more than 17 kOe intrinsic coercivity could be obtained by the aging process optimization. The microstructures and the fractures of the Nd-Fe-B magnets treated by the optimized aging process were also investigated by optical microscope, thermal field emission scanning electron microscopy and energy disperse spectroscopy. It was showed that the thin, continuous and smooth Nd-rich layer along the boundaries of the main crystal phase Nd2Fe14B could be formed by the optimized aging treatment and it resulted in the increase of the intrinsic coercivity of the Nd-Fe-B magnets.

Proliferative change and intestinal barrier dysfunction in intestinal mucosa of diabetes have been described, but the differentiation characteristics of intestinal epithelial cells (IECs) and the mechanisms in the IECs development remain unclear. To explore the intestinal epithelial constitution patterns and barrier function, the diabetic mouse model was induced by streptozotocin. Tight junctions between IECs were significantly damaged and the serum level of D-lactate was raised in diabetic mice (P