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miRNAs are important regulators of differentiation, development, and function of brown and beige fat cells. In this study, we identify the role of the miR-199a/214 cluster in the regulation of brown and beige adipocyte development and thermogenesis in vitro and in vivo. We show that expression of the miR-199a/214 cluster is dramatically decreased during brown and beige adipocyte differentiation and in response to cold exposure or β-adrenergic receptor activation. The cluster levels are significantly upregulated in the adipose tissues of obese mice and human subjects. Overexpression of the miR-199a/214 cluster suppresses brown adipocyte differentiation and inhibits thermogenic gene expression and mitochondrial respiration, whereas knockdown of the cluster increases thermogenic gene expression and mitochondrial function in beige adipocytes. In addition, inhibition of the miR-199a/214 cluster promotes beiging effects in vivo. We further show that miR-199a/214 suppresses brown adipocyte differentiation and beige fat development by directly targeting PRDM16 and peroxisome PGC-1α, two key transcriptional regulators of adipose browning. Together, these observations reveal that the miR-199a/214 cluster is a key negative regulator of brown and beige fat development and thermogenesis.

Diabetes is a noncommunicable widespread disease that poses the risk of severe complications in patients, with certain complications being life-threatening. Hepatitis C is an infectious disease that mainly causes liver damage, which is also a profound threat to human health. Hepatitis C virus (HCV) infection has many extrahepatic manifestations, including diabetes. Multiple mechanisms facilitate the strong association between HCV and diabetes. HCV infection can affect the insulin signaling pathway in liver and pancreatic tissue and change the profiles of circulating microRNAs, which may further influence the occurrence and development of diabetes. This review describes how HCV infection causes diabetes and discusses the current research progress with respect to HCV infection-related diabetes.

Graphical abstract, Since the 1950s, great efforts have been made to develop antiviral agents against many infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), human cytomegalovirus (HCMV), herpes simplex virus (HSV), and varicella-zoster virus (VZV). Among the list of nearly 106 antiviral agents approved in the past five decades, Prof. Erik De Clercq has contributed to the development of 7 antiviral drugs: tenofovir disoproxil fumarate (Viread®) for HIV and HBV treatment, tenofovir alafenamide (Vemlidy®) for HIV and HBV treatment, brivudine (Zostex®) for HSV-1 and VZV treatment, valacyclovir (Valtrex®) for HSV and VZV treatment, adefovir dipivoxil (Hepsera®) for HBV treatment, stavudine (Zerit®) for HIV treatment, and cidofovir (Vistide®) for treating HCMV retinitis in AIDS patients. In addition to the above antiviral drugs, his contributions include two anti-cancer drugs: rabacfosadine (Tanovea®-CA1) for canine lymphoma and plerixafor (Mozobil®) for multiple myeloma and non-Hodgkin’s lymphoma. These achievements are driven by his life-long passions for antiviral research and successful collaborations worldwide. To honor the 80th birthday of Prof. Erik De Clercq, this study highlights his scientific achievements and the importance of life-long passions and collaborations in the success of antiviral research and drug development.

Objectives Asymptomatic and symptomatic patients may transmit severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), but their clinical features and immune responses remain largely unclear. We aimed to characterise the clinical features and immune responses of asymptomatic and symptomatic patients infected with SARS‐CoV‐2. Methods We collected clinical, laboratory and epidemiological records of patients hospitalised in a coronavirus field hospital in Wuhan. We performed qualitative detection of anti‐SARS‐CoV‐2 immunoglobulin M (IgM) and immunoglobulin G (IgG) using archived blood samples. Results Of 214 patients with SARS‐CoV‐2, 26 (12%) were asymptomatic at hospital admission and during hospitalisation. Most asymptomatic patients were ≤ 60 years (96%) and females (65%) and had few comorbidities (, We studied a cohort of 26 asymptomatic and 188 symptomatic patients in a coronavirus field hospital. We found asymptomatic cases, mostly young females ≤ 60 years, in approximately 12% of nonseverely ill cases. More than 90% of cases experienced immunoglobulin M (IgM)/immunoglobulin G (IgG) seroconversion at the time of virus clearance, whereas the median time from the first virus‐positive tests to IgG/IgM seroconversion was significantly shorter in asymptomatic than in symptomatic patients. Compared with symptomatic patients, asymptomatic patients had lower IgG/IgM titres and plasma neutralisation capacity at the time of virus clearance.

Nucleoside and nucleotide analogues are essential antivirals in the treatment of infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). To celebrate the 80th birthday of Prof. Dr. Erik De Clercq on 28 March 2021, this review provides an overview of his contributions to eight approved nucleos(t)ide drugs: (i) three adenosine nucleotide analogues, namely tenofovir disoproxil fumarate (Viread®) and tenofovir alafenamide (Vemlidy®) against HIV and HBV infections and adefovir dipivoxil (Hepsera®) against HBV infections; (ii) two thymidine nucleoside analogues, namely brivudine (Zostex®) against HSV-1 and VZV infections and stavudine (Zerit®) against HIV infections; (iii) two guanosine analogues, namely valacyclovir (Valtrex®, Zelitrex®) against HSV and VZV and rabacfosadine (Tanovea®-CA1) for the treatment of lymphoma in dogs; and (iv) one cytidine nucleotide analogue, namely cidofovir (Vistide®) for the treatment of HCMV retinitis in AIDS patients. Although adefovir dipivoxil, stavudine, and cidofovir are virtually discontinued for clinical use, tenofovir disoproxil fumarate and tenofovir alafenamide remain the most important antivirals against HIV and HBV infections worldwide. Overall, the broad-spectrum antiviral potential of nucleos(t)ide analogues supports their development to treat or prevent current and emerging infectious diseases worldwide.

The COVID-19 pandemic causes severe morbidity and mortality. This multi-country study aimed to explore risk factors that drive mortality in COVID-19 patients who received neither dexamethasone nor remdesivir. We analyzed a cohort of 568 survivors and 507 non-survivors from China, European regions, and North America. Elderly males ≥70 years accounted for only 25% of survivors, but this rate was significantly higher in non-survivors from China (55%), European regions (63%), and North America (47%). Compared with survivors, non-survivors had more incidences of comorbidities such as cerebrovascular disease and chronic obstructive pulmonary disease (COPD, p-values

Due to the shortage of freshwater and energy crisis, seawater desalination with renewable energy has been proposed. A method for determining optimal planning of coastal hybrid renewable energy system (HRES) is proposed in this paper. Firstly, the system composition is introduced, and the virtual energy storage (VES) characteristics of the seawater reverse osmosis desalination plant is utilized to accommodate renewable energy generation. In order to reduce the system total cost, demand side management (DSM) measures are designed and applied to the regular electric load in the system. The methodology for planning optimization of the system is suggested, with objectives aiming at minimizing system total cost, end-user satisfaction loss caused by DSM, and tie-line power fluctuation. Since the problem has a mixed-integer manner, a modification of Non-dominated Sorting Genetic Algorithm-III (NSGA-III) is proposed. The newly-developed NSGA-III variant, named as MINSGA-III, is capable of solving mixed-integer optimization problem in an evolutionary algorithm fashion. This paper also presents several case studies to verify the feasibility and merits of the proposed method. The simulation results show that the proposed method is effective and feasible, and both DSM measures and VES approach have positive impact on the system modelling. The proposed MINSGA-III can effectively determine the solution of the multi-objective optimization problem.

The first case of COVID-19 was detected in Brazil on 25 February 2020. We report and contextualize epidemiological, demographic and clinical findings for COVID-19 cases during the first 3 months of the epidemic. By 31 May 2020, 514,200 COVID-19 cases, including 29,314 deaths, had been reported in 75.3% (4,196 of 5,570) of municipalities across all five administrative regions of Brazil. The R0 value for Brazil was estimated at 3.1 (95% Bayesian credible interval = 2.4–5.5), with a higher median but overlapping credible intervals compared with some other seriously affected countries. A positive association between higher per-capita income and COVID-19 diagnosis was identified. Furthermore, the severe acute respiratory infection cases with unknown aetiology were associated with lower per-capita income. Co-circulation of six respiratory viruses was detected but at very low levels. These findings provide a comprehensive description of the ongoing COVID-19 epidemic in Brazil and may help to guide subsequent measures to control virus transmission.

PurposeSARS-CoV-2 infects cells via the human Angiotensin-converting enzyme 2 (ACE2) protein. The genetic variation of ACE2 function and expression across populations is still poorly understood. This study aims at better understanding the genetic basis of COVID-19 outcomes by studying association between genetic variation in ACE2 and disease severity in the Iranian population.MethodsWe analyzed two large Iranian cohorts and several publicly available human population variant databases to identify novel and previously known ACE2 exonic variants present in the Iranian population and considered those as candidate variants for association between genetic variation and disease severity. We genotyped these variants across three groups of COVID-19 patients with different clinical outcomes (mild disease, severe disease, and death) and evaluated this genetic variation with regard to clinical outcomes.ResultsWe identified 32 exonic variants present in Iranian cohorts or other public variant databases. Among those, 11 variants are novel and have thus not been described in other populations previously. Following genotyping of these 32 candidate variants, only the synonymous polymorphism (c.2247G>A) was detected across the three groups of COVID-19 patients.ConclusionGenetic variability of known and novel exonic variants was low among our COVID-19 patients. Our results do not provide support for the hypothesis that exonic variation in ACE2 has a sizeable impact on COVID-19 severity across the Iranian population.

Despite the implementation of various vaccination programs, hepatitis B virus (HBV) poses a considerable health problem in Saudi Arabia. Insight on HBV evolutionary history in the region is limited. We performed a comprehensive epidemiological and phylogenetic reconstruction based on a large cohort of HBV infected patients. Three hundred and nineteen HBV-infected patients with different clinical manifestations, including inactive and active chronic carriers and patients with cirrhosis and hepatocellular carcinoma (HCC), were enrolled in this study. The full-length large S gene was amplified and sequenced. Phylogenetic analysis was performed to determine the genotype and subgenotypes of the isolates. Phylogenetic tree analysis revealed that genotype D is the most dominant genotype among patients. Moreover, this analysis identified two strains with genotype E isolated from active carriers. Detailed phylogenetic analyses confirmed the presence of four HBV D subgenotypes, D1 (93%, n = 296), D2 (0.02%, n = 5), D3 (0.003%, n = 1), and D4 (0.003%, n = 1). In addition, six genotype D strains were not assigned to any existing HBV D subgenotype. The large S gene of eight strains showed signatures of genotype recombination between the genotypes D and A and between D and E. Several strains harbored medically important point mutations at the protein level. Along with the dominance of the HBV genotype D, isolation of the E genotype and several recombinant strains from patients with Saudi Arabian origin is an essential result for decisions involving therapeutic measures for patients. Development of vaccines and detection of diagnostic escape mutations at antigenic epitopes on the HBsAg will be valuable to public health authorities. Furthermore, the diversity at the nucleotide and amino acid levels and different proportions of dN/dS at the PreS1, PreS2, and HBsAg reveal the selective pressure trend from inactive status towards advanced liver diseases. ispartof: Infection Genetics And Evolution vol:77 ispartof: location:Netherlands status: Published online

BACKGROUND Clogging of the suction tip frequently occurs during orthopedic surgery. We developed a novel anti-clog suction tip using 3D printing technology to improve orthopedic surgery efficiency. MATERIAL AND METHODS We studied the root causes of obstructions in suction tips currently employed in orthopedic surgery during actual surgical cases. CAD software and 3D printer was used to design, modify, and print the novel suction tip. The frequency of clogging, the frequency of replacement of the suction tip, the time lost in replacing suction tips or connecting tubes, surgical duration, intraoperative surgical blood loss, and the satisfaction scores for the suction tips as rated by the surgeons were compared between the novel suction tip and the conventional suction tip. Comparisons were made first in laboratory experiments using a simulant liquid and then during total hip replacement surgeries. RESULTS In the simulant liquid experiments, the novel suction tips showed significantly reduced frequency of complete clogging and decreased time spent removing all fluid in comparison to the conventional suction tips (p

A flexible power distribution modulation strategy for single-phase dual-input inverter was proposed in this paper. Taking the three-port DC-AC converter as an example, the DC ports include a high-voltage port VH and a low-voltage port VL, and the low-voltage port can send power to AC port even though the voltage is smaller than AC port. The power between the DC ports can also be distributed flexibly by controlling the duty cycle of current flowing through each DC port in each switching cycle. Power emitted from each DC port was analyzed and was verified by both simulation and experimental results. Finally, a 1.1kW prototype was built and tested to verify the practicality and effectiveness of the modulation strategy proposed in this paper.

Submodule (SM) fault detection and location (FDL) is essential for the reliable operation of modular multilevel converters (MMCs). Once SM failures occur, the capacitor voltages of faulty SMs will be out of control and deviate from the rated value. As analyzed in this paper, in normal state, the charging abilities of driving signals are constant in one fundamental period. Thus, the voltage variation of SMs in one fundamental period should coincide with the charging ability of driving signals applied to them. So this paper proposes an FDL method based on the capacitor voltage variation observations, which monitors the health state of SMs by comparing the expected voltage variations with the measured ones. The proposed method can detect and locate the faulty SM simultaneously in no more than two fundamental periods and requires no arm current measurement. Effectiveness of the proposed method and influence of capacitance inconsistency are validated by simulation results of a three-phase 101-level MMC in MATLAB/Simulink.

In the context of the current development of active distribution grids, flexible loads including seawater desalination have been introduced into the distribution grid as important resources in order to improve the ability of source-grid-load interaction. This paper focuses on the seawater desalination loads, and comprehensively considers the demand response uncertainty of desalination load caused by sudden external factors such as residential water consumption and reservoir water volume on the day of the demand response, as well as the characteristic due to the errors of short-term renewable energy forecasting. Afterwards, a multi-time scale optimal scheduling model that takes into account the uncertainty of demand response is proposed, and the risk cost of demand response uncertainty is analyzed and modeled. Besides, this paper introduces the source-grid-load interaction indicator into the optimization model to quantify the interaction effect, and uses the optimization algorithm to analyze examples in order to verify the effectiveness of the model, so as to provide technical support for enhancing the participation of seawater desalination in the source-grid-load interaction of the distribution network.

Nutrient resorption from senescing leaves to grain at physiological mature stage is critical to recover nutrients and improve grain production in semi-arid environment in south-eastern Australia. The aim of this study is to examine nitrogen (N) and phosphorus (P) resorption patterns and their effects on grain yield and quality of wheat in rotation with legume crops. A range of legume crops were grown in the field followed by one and two wheat crops in contrast with continuous wheat and canola crops with N fertiliser over 3 years. The soil N and P availability, flag leaf N and P nutrient status and resorption were measured in the first and second wheat crops after legume crops. Including legume crops in crop rotation increased soil available N concentration. Green leaf N concentration, and senesced leaf N and P concentrations increased as soil available N increased. However, N resorption efficiency (NRE) and P resorption efficiency (PRE) decreased as soil available N concentration increased. The NRE and PRE were positive correlated to grain yield and 1000-grain weight, but negative correlated to grain protein. The soil N benefit from legume crops can last more than one growing season. Under moisture stress conditions increased grain yield was associated with improved nutrient resorption efficiency via increased grain size regardless soil nutrient availability.

Soil emissions of nitrous oxide (N2O) are generally low in Australian semi-arid cropping systems, but can be reduced further by incorporating legumes into cereal-based rotations. We used automated and manual chambers to compare N2O emissions throughout a two-year legume-wheat field experiment. Two pulse crops [lupin (Lupinus angustifolius L.) and field pea (Pisum sativum L.)] and two forage legumes [vetch (Vicia sativa L.) and clover (a mixture of four Trifolium spp.)] were grown in the first year, followed by a wheat (Triticum aestivum L.) crop in the second year without additional nitrogen (N) fertilizer under either no-till or tillage systems. All legume crops were either (a) chemically terminated at anthesis (brown-manured, BM), or (b) cut for hay (forage legumes) or harvested for grain (pulses) (product-removed, PR). The fate of legume N in the BM treatment was traced using 15N labelled urea applied to soil in micro-plots. Results showed that N2O emissions during the legume and wheat phases were mostly unaffected by legume species, the exception being lower emissions from the BM clover pasture under the no-till treatment. Under the PR treatment, tillage tended to increase N2O emissions compared with the no-till treatment during both legume (121 vs. 104 g N2O-N ha−1 year−1) and wheat phases (91 vs. 79 g N2O-N ha−1 year−1). In contrast, a mixed result was found under the BM treatment with a significant tillage × crop management interaction during the legume phase, but no effect of tillage during the wheat phase. In general, the BM treatment promoted more N2O emissions due to more N input into soil compared to the PR treatment, with the impact extending into the subsequent wheat crop. The N2O emissions from the BM treatment during the legume (195 g N2O-N ha−1 year−1) and wheat phase (181 g N2O-N ha−1 year−1) were greater than those from the PR treatment for the corresponding phases (113 vs. 85 g N2O-N ha−1 year−1). The 15N study showed that the majority of legume-derived N was retained in the soil at the end of the legume phase and likely to be readily available for the subsequent cereal crop. The mitigation of N2O emissions derived from legumes in a semi-arid cereal-based cropping system can be optimized in a no-till system where product removal is practiced (cut for hay or harvested for grain) with legume species choice having little or no additional impact.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of coronavirus disease in 2019 (COVID-19). Genome surveillance is a key method to track the spread of SARS-CoV-2 variants. Genetic diversity and evolution of SARS-CoV-2 were analyzed based on 260,673 whole-genome sequences, which were sampled from 62 countries between 24 December 2019 and 12 January 2021. We found that amino acid (AA) substitutions were observed in all SARS-CoV-2 proteins, and the top six proteins with the highest substitution rates were ORF10, nucleocapsid, ORF3a, spike glycoprotein, RNA-dependent RNA polymerase, and ORF8. Among 25,629 amino acid substitutions at 8484 polymorphic sites across the coding region of the SARS-CoV-2 genome, the D614G (93.88%) variant in spike and the P323L (93.74%) variant in RNA-dependent RNA polymerase were the dominant variants on six continents. As of January 2021, the genomic sequences of SARS-CoV-2 could be divided into at least 12 different clades. Distributions of SARS-CoV-2 clades were featured with temporal and geographical dynamics on six continents. Overall, this large-scale analysis provides a detailed mapping of SARS-CoV-2 variants in different geographic areas at different time points, highlighting the importance of evaluating highly prevalent variants in the development of SARS-CoV-2 antiviral drugs and vaccines.

New breeding lines of Phalaris (Phalaris aquatica), cocksfoot (Dactylis glomerata) and tall fescue (Festuca arundinacea = syn. Lolium arundinaceum) are currently under evaluation for the selection of new cultivars for low rainfall environments. The aim was to test the relative tolerance of six elite genotypes of Phalaris, cocksfoot and tall fescue to aluminium and manganese toxicities in solution culture. Two solution culture experiments were conducted at aluminium concentrations of 0, 50, 100, 200 and 300 µM, or manganese (Mn) concentrations of 0, 2, 4, 6 and 8 mM in a basal nutrient solution at pH 4.5. Elite genotypes of cocksfoot, AVH48 Selection and Moroccan Fine, exist with improved tolerance to aluminium and Mn toxicities. Elite genotypes of Phalaris, particularly Northern Retainer, were superior to Sirolan at moderate to high aluminium concentrations in solution. There was little difference in the tolerance to aluminium and manganese toxicities between the elite genotypes and existing culti...

Droop control strategy is widely applied in ac microgrid to realize the seamless mode transition and achieve average power sharing among different inverters. However, there is a lack of analysis about the operation performance of droop control strategy in grid-connected mode. In this paper, grid fluctuation and control accuracy of reactive power are illustrated to be the main influence factors for power flow control according to the small-signal model. The feedforward of grid frequency and voltage magnitude is proposed to mitigate the impacts of grid fluctuation on power flow control. Since the feedforward items are achieved through the synchronous reference frame phase-locked loop with the input of filter capacitor voltage, extra sensors for grid voltage are avoided. Moreover, voltage magnitude control is introduced to enhance the control accuracy of reactive power flow. In addition, modified droop control loops are also proposed to improve the system stability. With the implementation of the proposed control scheme, improved power flow control and enhanced system stability are achieved with the feature of seamless mode transition maintained. Finally, the major contribution of this paper is verified by a laboratory prototype.

Grain legumes, such as lupins and field peas, are one of key rotation components in Australian agricultural systems, supplying nitrogen (N) to following crops, and potentially increasing farm profitability. In this study, we used a modelling approach to investigate the profitability of incorporating field pea ( Pisum sativum ) and narrowleaf lupin ( Lupinus angustifolius ) in cereal-based (wheat/canola) cropping systems in southern New South Wales (NSW), Australia. We calibrated and validated the Agricultural Production Systems sIMulator (APSIM) with three-year's experimental data to predict yields of field pea and lupin, and N contribution of grain legumes in cereal-based (wheat/canola) crop rotations. We conducted a gross margin analysis to analyse the profitability of adding grain legumes into cereal-based crop rotations at both crop and rotation levels. The simulated results showed that field pea and lupin could contribute 30–65 kg N ha − 1 to the next crop and 60–110 kg N ha − 1 to subsequent crops (wheat/canola) for two years, corresponding to 30–55% and 60–86% of net N inputs of legume-fixed N, respectively. This greatly increased the yields and profitability of wheat/canola in the following two years. Including grain legumes in cereal-based crop rotations was more profitable than non-legume crop rotations, even though the grain legumes were less profitable than wheat/canola in the year of growing. However, N and economic benefits would be reduced to zero if N fertilizer applied to wheat/canola was over the optimal level, i.e. 100–125 kg N ha − 1 in terms of N benefit, or 75 kg N ha − 1 for farm-economic profit. In general, incorporation of grain legumes into cereal-based crop rotations offers an obvious N benefit to subsequent crops and provides an economic benefit for farmers (reduced N applications). This suggests that the contribution of grain legumes to cereal-based cropping systems should be assessed as part of a rotation rather than as a stand-alone crop.

Black Vertosols of subtropical Australia emit large amounts of nitrous oxide (N2O) to the atmosphere under fertilizer-applied grain cropping compared to other Australian cropping soils. N2O emissions can be mitigated by either reducing fertilizer N inputs or altering crop rotation systems. In this study, the WNMM agroecosystem model was used to investigate the responses of N2O emissions from four different crop rotation systems including canola-wheat-barley (T1CaWB), chickpea-wheat-barley (T3CpWB), chickpea-wheat-chickpea (T4CpWCp), and chickpea-Sorghum (T5CpS) under projected future climate change scenarios on a black Vertosol at Tamworth, New South Wales, Australia. In simulations of the twenty-first century under four different scenarios for atmospheric greenhouse gas concentrations, the annual N2O emissions from the four cropping systems increased with greenhouse gas forcing of the climate. The annual N2O emissions from T4CpWCp (with no fertilizer N application) were the most sensitive to climate change, with 14.3–61.9% increase compared with historic simulations of 1952–2014. The simulated T5CpS treatment (with a long fallow) kept the gross margin-scaled N2O emissions below 1 g N per Australian dollar under all climate change scenarios. This suggests that the inclusion of a long fallow in a crop rotation system can slow down the pace of increasing gross margin-scaled N2O emissions in response to climate change. Our simulation results also imply that legume rotations as mitigation options on N2O emissions may not be resilient to the future changing climate even though they can greatly reduce N2O emissions under the current climate.

This study examined the response of forage crops to composted dairy waste (compost) applied at low rates and investigated effects on soil health. The evenness of spreading compost by commercial machinery was also assessed. An experiment was established on a commercial dairy farm with target rates of compost up to 5 t ha−1applied to a field containing millet [Echinochloa esculenta(A. Braun) H. Scholz] and Pasja leafy turnip (Brassicahybrid). A pot experiment was also conducted to monitor the response of a legume forage crop (vetch;Vicia sativaL.) on three soils with equivalent rates of compost up to 20 t ha−1with and without ‘additive blends’ comprising gypsum, lime or other soil treatments. Few significant increases in forage biomass were observed with the application of low rates of compost in either the field or pot experiment. In the field experiment, compost had little impact on crop herbage mineral composition, soil chemical attributes or soil fungal and bacterial biomass. However, small but significant increases were observed in gravimetric water content resulting in up to 22.4 mm of additional plant available water calculated in the surface 0.45 m of soil, 2 years after compost was applied in the field at 6 t ha−1dried (7.2 t ha−1undried), compared with the nil control. In the pot experiment, where the soil was homogenized and compost incorporated into the soil prior to sowing, there were significant differences in mineral composition in herbage and in soil. A response in biomass yield to compost was only observed on the sandier and lower fertility soil type, and yields only exceeded that of the conventional fertilizer treatment where rates equivalent to 20 t ha−1were applied. With few yield responses observed, the justification for applying low rates of compost to forage crops and pastures seems uncertain. Our collective experience from the field and the glasshouse suggests that farmers might increase the response to compost by: (i) increasing compost application rates; (ii) applying it prior to sowing a crop; (iii) incorporating the compost into the soil; (iv) applying only to responsive soil types; (v) growing only responsive crops; and (vi) reducing weed burdens in crops following application. Commercial machinery incorporating a centrifugal twin disc mechanism was shown to deliver double the quantity of compost in the area immediately behind the spreader compared with the edges of the spreading swathe. Spatial variability in the delivery of compost could be reduced but not eliminated by increased overlapping, but this might represent a potential 20% increase in spreading costs.

Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials. Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials.

Introduction: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of highly active antiretroviral therapy against HIV-1 infections. Here, we provide a comprehensive overview of approved and emerging NNRTIs. Areas covered: This review covers the latest trend of NNRTIs regarding their pharmacodynamics, pharmacokinetics, mechanisms of drug action, drug resistance as well as new applications such as two-drug regimens and long-acting formulations. Expert opinion: Since the first NNRTI, nevirapine, was approved in 1996, antiviral drug discovery led to the approval of seven NNRTIs, including nevirapine, delavirdine (discontinued), etravirine, elsulfavirine, efavirenz, rilpivirine, and doravirine. The latter three compounds with favorable pharmacodynamic profiles and minimal adverse effects are often combined with one integrase inhibitor or two NRTIs in once-daily fixed-dose tablets. NNRTI-anchored regimens have been approved as initial therapies in treatment-naive patients (efficacy: 72% to 86%) or maintaining therapies in virologically-suppressed patients (efficacy: 91% to 95%). Future development of NNRTIs includes: (i) better resistance and cross-resistance profiles; (ii) reduction of drug burden by optimizing two-drug or three-drug combinations; and (iii) improvement of patient adherence by novel long-acting formulations with weekly or monthly administration. Overall, NNRTIs play an important role in the management of HIV-1 infections, especially in resource-limited countries.

Background As an important anti-HBV drug, pegylated interferon α (PegIFNα) offers promising clinical efficacy, but biomarkers that accurately forecast treatment responses are yet to be elucidated. Here, we evaluated whether HBV RNA could act as an early monitor of pegylated interferon responses. Methods We analyzed a phase 3, multicenter, randomized cohort of 727 HBeAg-positive non-cirrhotic patients receiving a 48-week treatment of PegIFNα-2a or PegIFNα-2b and a 24-week treatment-free follow-up. Serum levels of HBV RNA, HBV DNA, HBeAg, and HBsAg were measured at weeks 0, 12, 24, 48, and 72. Results HBeAg seroconversion and HBsAg loss at week 72 were observed in 217 (29.8%) and 21 (2.9%) patients, respectively. During the 48-week treatment, HBV RNA decreased more rapidly than HBV DNA and HBsAg, but HBV RNA and HBeAg shared similar dynamics with positive correlations. Multivariate regression analyses consistently revealed the significance of HBV RNA at weeks 0, 12, 24, and 48 to monitor HBeAg seroconversion but not HBsAg loss. Although baseline HBV RNA only showed a modest AUC performance, HBV RNA with a significant increase of AUC at week 12 outperformed other HBV biomarkers to forecast HBeAg seroconversion (p value Conclusion HBV RNA at week 12 is an effective monitor of HBeAg seroconversion in HBeAg-positive patients treated with pegylated interferons.

In order to realize the calculation of the line loss of the distribution network with complex structure and low-voltage station area, this paper presents a line loss calculation method based on BP neural network with genetic algorithm optimization. The proposed method is based on the actual operation data of the distribution network. Firstly, build an error back propagation (BP) neural network model to compute the theoretical line loss of the distribution network, then use genetic algorithm (GA) to optimize the neural network and establish the GA-BP model. Based on the proposed model, the calculation demonstrates that the neural network line loss rate calculation model with genetic algorithm optimization shows better performance than the single BP neural network model, such as better nonlinear fitting ability and higher calculation accuracy. Therefore, the line loss calculation method proposed in this paper based on the BP neural network with the genetic algorithm optimization can improve the accuracy of the distribution network line loss rate calculation model.

Soil pH is seldom uniform with depth, rather it is stratified in layers. The soil surface (0–0.02 m) commonly exhibits relatively high pH and overlies a layer of acidic soil of 0.05–0.15 m deep, termed an acidic subsurface layer. Commercial and research sampling methods that rely on depth increments of 0.1 m either fail to detect or under report the presence or magnitude of pH stratification. The occurrence of pH stratification and the presence of acidic subsurface layers may cause the extent of acidity in NSW agricultural land to be underestimated. Though the cause of pH stratification in agricultural systems is well understood, the effect on agricultural production is poorly quantified due in part to inadequate sampling depth intervals resulting in poor identification of acidic subsurface layers. Although liming remains the best method to manage acidic soil, current practices of low pH targets (pHCa 5), inadequate application rates and no or ineffective incorporation have resulted in the continued formation of acidic subsurface layers. Regular monitoring in smaller depth increments (0.05 m), higher pH targets (pHCa > 5.5) and calculation of lime rate requirements that account for application method are required to slow or halt soil degradation by subsurface acidification. If higher pH is not maintained in the topsoil, the acidification of subsurface soils will extend further into the profile and require more expensive operations that mechanically place amendments deep in the soil. Although the use of organic amendments has shown promise to enhance soil acidity amelioration with depth, the longevity of their effect is questionable. Consequently, proactive, preventative management of topsoil pH with lime addition remains the most cost-effective solution for growers.

Cover crop species are usually grown to control weeds. After cover crop harvest, crop residue is applied on the ground to improve soil fertility and crop productivity. Little information is available about quantifying the contributions of cover crop application to soil total carbon (C) and nitrogen (N) contents in temperate Australia. Here, we selected eight cover crop treatments, including two legume crops (vetch and field pea), four non-legume crops (rye, wheat, Saia oat, and Indian mustard), a mixture of rye and vetch, and a nil-crop control in temperate Australia to calculate the contributions of cover crops (crop growth + residue decomposition) to soil C and N contents. Cover crops were sown in May 2009 (autumn). After harvest, the crop residue was placed on the soil surface in October 2009. Soil and crop samples were collected in October 2009 after harvest and in May 2010 after 8 months of residue decomposition. We examined cover crop residue biomass, soil and crop total C and N contents, and soil microbial biomass C and N contents. The results showed that cover crop application increased the mean soil total C by 187–253 kg ha−1 and the mean soil total N by 16.3–19.1 kg ha−1 relative to the nil-crop treatment, except for the mixture treatment, which had similar total C and N contents to the nil-crop control. Cover crop application increased the mean soil microbial biomass C by 15.5–20.9 kg ha−1 and the mean soil microbial biomass N by 4.5–10.2 kg ha−1. We calculated the apparent percentage of soil total C derived from cover crop residue C losses and found that legume crops accounted for 10.6–13.9 %, whereas non-legume crops accounted for 16.4–18.4 % except for the mixture treatment (0.2 %). Overall, short-term cover crop application increased soil total C and N contents and microbial biomass C and N contents, which might help reduce N fertilizer use and improve sustainable agricultural development.

The introduction of highly potent direct-acting antivirals (DAAs) has revolutionized hepatitis C virus treatment. Nevertheless, viral eradication worldwide remains a challenge also in the era of DAA treatment, because of the high associated costs, high numbers of undiagnosed patients, high re-infection rates in some risk groups and suboptimal drug efficacies associated with host and viral factors as well as advanced stages of liver disease. A correct determination of the HCV genotype allows administration of the most appropriate antiviral regimen. Additionally, HCV genetic sequencing improves our understanding of resistance-associated variants, either naturally occurring before treatment, acquired by transmission at HCV infection, or emerging after virological failure. Because treatment response rates, and the prevalence and development of drug resistance variants differ for each DAA regimen and HCV genotype, this review summarizes treatment opportunities per HCV genotype, and focuses on viral genetic sequencing to guide clinical decision making. Although approval of the first pan-genotypic DAA-only regimen is expected soon, HCV genetic sequencing will remain important because when DAA therapies fail, genotyping and resistance testing to select a new active DAA combination will be essential. Copyright © 2016 John Wiley & Sons, Ltd.

Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2'-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2'-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide. ispartof: Clinical Microbiology Reviews vol:29 issue:3 pages:695-747 ispartof: location:United States status: published

Grazing exclusion is one of the common grassland management strategies to restore degraded grasslands. The effectiveness of grazing exclusion on sequestering soil organic carbon, increasing total nitrogen and improving soil biological activity has been documented in literature. Few studies, however, have examined the responses of phosphorus (P) fractions and arbuscular mycorrhizal fungi (AMF) diversity to long-term grazing exclusion. In this study, the variations of soil chemical properties, the status of inorganic and organic P fractions in the rhizosphere soil, and the AMF diversity in roots of Leymus chinensis , Stipa krylovii and Cleistogenes squarrosa and in bulk soils were investigated in continuously grazed and ungrazed paddocks (exclusion from grazing for 10–12 years) on typical and meadow steppes in Inner Mongolia, aiming to evaluate the effectiveness of grazing exclusion in improving AMF diversity and soil P status. Grazing exclusion altered plant species compositions and increased aboveground biomass and ground cover, resulting in increased concentrations of soil organic carbon and total nitrogen. The concentration of total phosphorus increased in typical steppes but reduced in meadow steppes, while the concentrations of available P and most P fractions remained unchanged or reduced following 10–12 years of grazing exclusion. Grazing exclusion improved AMF colonization in meadow steppes, but not in typical steppes, attributing to the differences in soil quality, plant species, and AMF phylotypes between two types of steppes. AMF diversity was positively correlated with soil pH, concentrations of soil total nitrogen, total organic carbon, total P, Ca 10 –P, medium labile organic P, and the activity of alkaline phosphatase, indicating that, on semi-arid steppes in northern China, improved soil conditions would increase the AMF diversity, thus enhancing the productivity of the steppe ecosystem. However, changes of soil AMF phylotypes due to overgrazing would be detrimental to this fragile ecosystem.

In grassland, introduction of legume potentially can play a significant role in increasing soil carbon (C) and nitrogen (N) storage through increasing biomass C input. It has been reported that grass–legume ratio (GLR) is important in assessing benefits of grass–legume mixtures, however, little is known about how GLR affects soil C and N storage. As an effort to understand the effects and mechanisms of GLR on soil carbon and nitrogen storage, biological nitrogen fixation (BNF) by legumes, and changes in C and N storage in plants and soil were examined under swards with different densities of grasses and legumes over 4 years in a temperate steppe grassland. Results showed that total N storage in 0–40 and overall 0–150 cm soil depths varied as GLR changed, reaching peak values when the GLR was equivalent to 1:1. Increased relative legume abundance significantly enhanced soil C storage in both 0–40 and 0–150 cm soil depths, which was primarily attributed to an increase of aboveground biomass C. Soil organic C and total N varied with GLR changes, leading to stoichiometric shifts in soil C:N ratios, possibly influencing soil C storage through changing plant community structure and soil biochemistry. It is suggested that introducing legumes in steppe grasslands with a GLR of 1:1 could increase resources use efficiency and improve the sustainability of the environment.

The droop-based control strategy is widely applied in the interfacing inverters for distributed generation. This can be a problem since low-frequency stability issues may be encountered in droop-based microgrid. The objective of this paper is to classify, evaluate and compare various low-frequency damping methods. First, low-frequency stability problems are analyzed and an equivalent model of a droop-controlled inverter is investigated to classify the damping methods into the source-type damping strategies and the impedance-type damping strategies. Moreover, the lead-lag compensation network insertion control is proposed as a beneficial part of the source-type damping strategies. Then, the advantages and disadvantages of the different types of damping methods are theoretically evaluated and experimentally tested. Furthermore, the damping methods are comprehensively compared to illustrate the application field of each method. Finally, the synthesis of different damping methods to enhance the low-frequency stability is discussed and experimental validation is presented.

In spite of the impressive diversity of multi-factors fuzzy time series models, there is still a burning need to develop models that can handle the uncertainty inherent in certain data with some certain methods and obtain high forecasting accuracy. This paper proposes a novel multi-granularity combined prediction model for multi-factors fuzzy time series forecasting. The proposed model utilizes the clustering algorithm to generate different lengths of intervals, and forecasts the fuzzy trend in different granular spaces. It calculates the final forecasted value by using the forecasted fuzzy trend in each granular space and the optimal weighting vector obtained by particle swarm techniques. The proposed model can transform the uncertain problem to a certain problem through the granular computing theory. The experiments show that the presented model can not only obtain higher forecasting accuracy than several existing methods to forecast the Taiwan Stock Exchange Capitalization Weighted Stock Index (TAIEX) and the civilian unemployment rate, but also capture and interpret the fuzzy trend.

The accumulation of carbon (C) in soil as organic matter (SOM) is considered to be a win–win situation for agriculture and the environment. Retention of crop and pasture residues should contribute to this accumulation of organic C in soil. However the retention of crop stubble has not necessarily resulted in increases in soil organic matter in long term field trials in southern New South Wales (NSW), Australia. Even under permanent pasture, annual or perennial, the rates of accumulation of soil organic matter are only about 500 kg C/ha/year at best in the environment of southern NSW. Hence the C accumulation rates in soil are not likely to generate a significant income stream from C trading. Further, in the mixed farming systems of the inland areas, the traditional rotation has relied upon the build up of organic matter during the pasture phase and the mineralisation of nitrogen (N) (and hence C) during the cropping phase. A change from this system requires increased reliance on the use of N fertiliser. Either way, an additional problem is that the accumulation of organic matter during a pasture phase, or the use of N fertiliser, is commonly associated with soil acidification, requiring the application of limestone and the release of CO2 in order to maintain agricultural productivity. In addition to these soil based processes, the climatic variability that is commonly experienced in the semi-arid environment of southern NSW means that year to year variability in dry matter return to soil and in decomposition rates of residues will be relatively large. The net result is that the signal to noise ratio of any trend in SOM accumulation is low.

We hypothesised that a) species with greater acid soil tolerance have an increased capacity to utilise incipient rainfall; and b) liming increases the productivity and the ability of pasture species to utilise available water resources in the profile of an acid soil. A field experiment was established on a moderately acidic yellow Kandosol and monitored over 5 years. Five perennial pasture species including lucerne (Medicago sativa L.), phalaris (Phalaris aquatica L.), chicory (Cichorium intybus L.), tall fescue (Festuca arundinacea Schreb.) and cocksfoot (Dactylis glomerata L.), were sown in monocultures with and without 2.9 t/ha lime. Both lucerne and phalaris were more persistent than chicory, tall fescue and cocksfoot under severe drought, despite both being considered sensitive to soil acidity. Surface liming increased the soil water deficit by up to 27 mm at 0.75–1.65 m under perennial pastures compared to unlimed treatments, despite lime having no physical presence at that depth. Lime increased lucerne, phalaris and cocksfoot cumulative herbage biomass by 150, 30 and 20 %, respectively, but had no significant effect on chicory or tall fescue biomass. The two most acid-sensitive species, lucerne and phalaris, were more resilient under drought despite the acidic nature of the soil. We contend that species sensitive to acidity can be a valuable addition to pastures on acid soils. Lime used in conjunction with deep-rooted perennial species is likely to maximise the ability of pastures to utilise scarce available soil water reserves.

Newly developed candidate cultivars of cocksfoot (Dactylis glomerata L.), phalaris (Phalaris aquatica L.) and tall fescue (Festuca arundinacea Schreb. = syn. L. arundinaceum (Schreb) Darbysh.) were evaluated over four years for persistence and productivity against current commercial cultivars in small plots at five locations selected for lower and less reliable rainfall and difficult soils (low pH and high Al) in south-eastern Australia known to be marginally too dry for these grass species. The five locations were - representing summer dominant rainfall, Inverell, in northern New South Wales (NSW); - representing uniform rainfall; Trungley Hall, (medium rainfall), and Beckom (lower rainfall) both in southern NSW; and; representing a winter dominant pattern - Eversley, (higher rainfall), and Bealiba, (lower rainfall), in central Victoria. The objective was to determine if the new candidate cultivars were more likely to persist and to be productive than current commercial cultivars. The study showed that most phalaris and cocksfoot treatments were highly productive in high rainfall years at one or both sites in southern NSW. However, all treatments had become much less productive by the end of the experimental period due to plant loss under hot, dry conditions in the final summer. At Bealiba in central Victoria, cocksfoot was the most productive species with several cocksfoot treatments of both subsp. hispanica and subsp. glomerata still present at the final harvest despite a hot and dry final summer-autumn. Tall fescue was the most productive species in the two higher rainfall environments (Inverell, Eversley) although most treatments of all species performed well at those sites. Continental tall fescues were more productive on average than Mediterranean tall fescues at the strongly acidic Eversley site. As a result of this work, two of the new cocksfoot candidates (Moroccan Fine and AVH48 Selection) and one of the tall fescue candidates (Summer Active 1) have been licensed for commercial development and release.

Emerging evidence indicates that long noncoding RNAs (lncRNAs) regulate various biological processes, especially innate and adaptive immunity. However, the relationship between lncRNAs and the interferon (IFN) pathway remains largely unknown. Here, we report that lncRNA ITPRIP-1 (lncITPRIP-1) is involved in viral infection and plays a crucial role in the virus-triggered IFN signaling pathway through the targeting of melanoma differentiation-associated gene 5 (MDA5). LncITPRIP-1 can be induced by viral infection, which is not entirely dependent on the IFN signal. Besides, there is no coding potential found in the lncITPRIP-1 transcript. LncITPRIP-1 binds to the C terminus of MDA5, and it possesses the ability to boost the oligomerization of both the full length and the 2 caspase activation and recruitment domains of MDA5 in a K63-linked polyubiquitination-independent manner. Amazingly, we also found that MDA5 can suppress hepatitis C virus (HCV) replication independently of IFN signaling through its C-terminal-deficient domain bound to viral RNA, in which lncITPRIP-1 plays a role as an assistant. In addition, the expression of lncITPRIP-1 is highly consistent with MDA5 expression, indicating that lncITPRIP-1 may function as a cofactor of MDA5. All the data suggest that lncITPRIP-1 enhances the innate immune response to viral infection through the promotion of oligomerization and activation of MDA5. Our study discovers the first lncRNA ITPRIP-1 involved in MDA5 activation.IMPORTANCE Hepatitis C virus infection is a global health issue, and there is still no available vaccine, which makes it urgent to reveal the underlying mechanisms of HCV and host factors. Although RIG-I has been recognized as the leading cytoplasmic sensor against HCV for a long time, recent findings that MDA5 regulates the IFN response to HCV have emerged. Our work validates the significant role of MDA5 in IFN signaling and HCV infection and proposes the first lncRNA inhibiting HCV replication by promoting the activation of MDA5 and mediating the association between MDA5 and HCV RNA, the study of which may shed light on the MDA5 function and treatment for hepatitis C patients. Our suggested model of how lncITPRIP-1 orchestrates signal transduction for IFN production illustrates the essential role of lncRNAs in virus elimination.

In the above paper, the authors realize that an error inadvertently appeared in the funding section on p. 895. Where "This study was supported by the National Natural Science Foundation of China Science Fund Project (grant no. 30960389 and 8176010097)" was written, the application number 8176010097 was featured incorrectly: This should have been written as grant no. 81760030. Therefore, this sentence in the funding section should have read as follows: "This study was supported by the National Natural Science Foundation of China Science Fund Project (grant nos. 30960389 and 81760030)". The authors regret this error was not noticed prior to the publication, and apologize to their funding body and to the readership of the Journal for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 42:883-896, 2018; DOI: 10.3892/ijmm.2018.3682].

Human innate immunity responds to viral infection by activating the production of interferons (IFNs) and proinflammatory cytokines. The mitochondrial adaptor molecule MAVS plays a critical role in innate immune response to viral infection. In this study, we show that TRIM21 (tripartite motif-containing protein 21) interacts with MAVS to positively regulate innate immunity. Under viral infection, TRIM21 is upregulated through the IFN/JAK/STAT signaling pathway. Knockdown of TRIM21 dramatically impairs innate immune response to viral infection. Moreover, TRIM21 interacts with MAVS and catalyzes its K27-linked polyubiquitination, thereby promoting the recruitment of TBK1 to MAVS. Specifically, the PRY-SPRY domain of TRIM21 is the key domain for its interaction with MAVS, while the RING domain of TRIM21 facilitates the polyubiquitination chains of MAVS. In addition, the MAVS-mediated innate immune response is enhanced by both the PRY-SPRY and RING domains of TRIM21. Mutation analyses of all the lysine residues of MAVS further revealed that Lys325 of MAVS is catalyzed by TRIM21 for the K27-linked polyubiquitination. Overall, this study reveals a novel mechanism by which TRIM21 promotes the K27-linked polyubiquitination of MAVS to positively regulate innate immune response, thereby inhibiting viral infection.IMPORTANCE Activation of innate immunity is essential for host cells to restrict the spread of invading viruses and other pathogens. MAVS plays a critical role in innate immune response to RNA viral infection. In this study, we demonstrated that TRIM21 targets MAVS to positively regulate innate immunity. Notably, TRIM21 targets and catalyzes K27-linked polyubiquitination of MAVS and then promotes the recruitment of TBK1 to MAVS, leading to upregulation of innate immunity. Our study outlines a novel mechanism by which the IFN signaling pathway blocks RNA virus to escape immune elimination.

Candida species are a major cause of human mucosal and deep tissue fungal infections, but few antifungal treatments are available. Here, we showed that lycosin-I, a peptide isolated from venom of the spider Lycosa singoriensis, acted as a potent antifungal inhibitor against Candida species. The MIC50 values of lycosin-I reached 8 μg/mL to treat fluconazole-susceptible and fluconazole-resistant C. tropicalis isolates. Time-kill kinetics assays revealed that after a 2-hour exposure, lycosin-I reduced colony-forming units/mL in fluconazole-susceptible and fluconazole-resistant C. tropicalis isolates approximately 70%. Furthermore, salinity tolerance assays suggested that even in the presence of Mg2+, lycosin-I maintained its potent antifungal ability at a high concentration. When the concentration of lycosin-I was increased from 1 × MIC to 8 × MIC, a significant decrease of the biofilm metabolic activity was observed in both fluconazole-susceptible and fluconazole-resistant C. tropicalis isolates. Moreover, the biofilm inhibitory concentration 50 (BIC50) and the biofilm eradicating concentration 50 (BEC50) were approximately 32 μg/mL and 128 μg/mL, respectively. Confocal laser scanning microscopy showed the localization of CY5-labeled lycosin-I mainly in the cell cytoplasm, and lycosin-I was likely to be localized in the cytoplasm after its transportation across the cell wall and membrane. Overall, our work shows that lycosin-I is a potent antifungal agent with a high efficacy, a high salinity tolerance, and potent anti-biofilm properties.

A network of 21 experiments was established across nine countries on four continents and spanning both hemispheres, to evaluate the relative performance of early generation perennial cereal material derived from wheat, rye, and barley and to inform future breeding strategies. The experimental lines were grown in replicated single rows, and first year production and phenology characteristics as well as yield and persistence for up to three years were monitored. The study showed that the existing experimental material is all relatively short-lived (≤3 years), with environments that are milder in summer and winter generally conferring greater longevity. No pedigree was superior across this diverse network of sites although better performing lines at the higher latitude sites were generally derived from Thinopyrum intermedium. By contrast, at lower latitudes the superior lines were generally derived from Th. ponticum and Th. elongatum parentage. The study observed a poor relationship between year 1 performance and productivity in later years, highlighting the need for perennial cereal material with greater longevity to underpin future experimental evaluation, and the importance for breeding programs to emphasize post-year 1 performance in their selections. Hybrid lines derived from the tetraploid durum wheat generally showed greater longevity than derivatives of hexaploid wheat, highlighting potential for greater use of Triticum turgidum in perennial wheat breeding. We advocate a model in future breeding initiatives that develops perennial cereal genotypes for specific target environments rather than a generic product for one global market. These products may include a diversity of cultivars derived from locally adapted annual and perennial parents. In this scenario the breeding program may have access to only a limited range of adapted perennial grass parents. In other situations, such as at very high latitude environments, perennial crops derived from barley or rye may have a better chance of success than those derived from wheat. In either case, development and selection of the perennial parent for adaptation to local environments would seem fundamental to success.

The present study aimed to investigate the effect of the expression of interleukin (IL)-18 and related markers on deep venous thrombosis (DVT) to examine their correlation. Sprague-Dawley rats of different models were established and were randomly assigned into three groups. The expression of IL-18, nuclear factor (NF)-κB and von Willebrand factor (vWF) were detected in blood samples. The inferior vena cava (IVC) was ligated to establish the DVT model. Rat IL-18 overexpression and inhibition vectors were constructed. The expression levels of IL-18 and related markers in the venous wall were compared between the model group and the control group using reverse transcription-quantitative polymerase chain reaction and western blot analyses. Following the culture of human umbilical vein endothelial cells (HUVECs), IL-18 was added to the cells, following which the growth of the HUVECs, and changes in vWF and other endothelial functional markers were analyzed. The IVC model demonstrated complete thrombosis at 8 h and stable thrombosis at 24 h. At 24 h following model establishment, the expression levels of IL-18, NF-κB and vWF were high in the blood samples with the occurrence and development of thrombosis (P

Activation of innate immunity is essential for host cells to restrict the spread of invading viruses and other pathogens. However, attenuation or termination of signaling is also necessary for preventing immune-mediated tissue damage and spontaneous autoimmunity. Here, we identify nucleotide binding oligomerization domain (NOD)-like receptor X1 (NLRX1) as a negative regulator of the mitochondrial antiviral signaling protein (MAVS)-mediated signaling pathway during hepatitis C virus (HCV) infection. The depletion of NLRX1 enhances the HCV-triggered activation of interferon (IFN) signaling and causes the suppression of HCV propagation in hepatocytes. NLRX1, a HCV-inducible protein, interacts with MAVS and mediates the K48-linked polyubiquitination and subsequent degradation of MAVS via the proteasomal pathway. Moreover, poly(rC) binding protein 2 (PCBP2) interacts with NLRX1 to participate in the NLRX1-induced degradation of MAVS and the inhibition of antiviral responses during HCV infection. Mutagenic analyses further revealed that the NOD of NLRX1 is essential for NLRX1 to interact with PCBP2 and subsequently induce MAVS degradation. Our study unlocks a key mechanism of the fine-tuning of innate immunity by which NLRX1 restrains the retinoic acid-inducible gene I-like receptor (RLR)-MAVS signaling cascade by recruiting PCBP2 to MAVS for inducing MAVS degradation through the proteasomal pathway. NLRX1, a negative regulator of innate immunity, is a pivotal host factor for HCV to establish persistent infection. IMPORTANCE Innate immunity needs to be tightly regulated to maximize the antiviral response and minimize immune-mediated pathology, but the underlying mechanisms are poorly understood. In this study, we report that NLRX1 is a proviral host factor for HCV infection and functions as a negative regulator of the HCV-triggered innate immune response. NLRX1 recruits PCBP2 to MAVS and induces the K48-linked polyubiquitination and degradation of MAVS, leading to the negative regulation of the IFN signaling pathway and promoting HCV infection. Overall, this study provides intriguing insights into how innate immunity is regulated during viral infection.

Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1–6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (¥99% amino acid identity) and an additional 24% as pan-genotypic conserved (¥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%–0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be genotype-specific or geographically tailored. ispartof: Viruses vol:7 issue:9 pages:5018-5039 ispartof: location:Switzerland status: published

Perennial grasses provide forage and environmental benefits in the agricultural systems of southern Australia, but persistent cultivars are lacking for the lower rainfall inland margins (