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Hepatitis A virus (HAV) live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans. Recently, type I interferon (IFN) receptor-deficient mice were shown to be susceptible to HAV infection. Herein, we sought to determine the infection and replication dynamics of the H2 in Ifnar

Yellow fever virus (YFV), the prototype of the Flavivirus genus, can cause devastating yellow fever disease. Although it is preventable by vaccination, there are still tens of thousands of yellow fever cases per year, and no approved antiviral medicine is available.

The suspected link of Zika virus (ZIKV) to birth defects led the World Health Organization to declare ZIKV a Public Health Emergency of International Concern. ZIKV has been identified to have two dominant phylogenetic lineages, African and Asian.

The study aimed to improve polysaccharide-based packaging to extend the shelf life of fresh produce; a composite film with antimicrobial function was developed and tested. The packaging film is a blend of agar, a film-forming substrate; carrageenan, as a reinforcing agent; glycerol, as a plasticizer; and Nisin, an antimicrobial agent. The film was evaluated for its antibacterial, mechanical, and barrier properties at different humidity levels, using fresh-cut watermelon as the test food material. The film effectively inhibited the growth of Staphylococcus aureus and Listeria monocytogenes. Under relative humidity of 20%, 50%, and 90%, the tensile strength of the antibacterial film containing 0.28% Nisin was 23.08 ± 0.65, 16.09 ± 1.73, and 6.52 ± 0.56 MPa, respectively, and the film also had excellent barrier and heat-sealing properties. The packaging test using fresh-cut watermelon sealed in the antibacterial film containing 0.28% Nisin, under controlled atmosphere storage at either 4 °C or 20 °C, effectively inhibited microbial colonization in the melon and slowed the deterioration of the fruit, as indicated by measures of hardness, weight loss, and soluble solids. This method can extend the shelf life of fresh-cut fruit and provide a reference for further research on polysaccharide-based protective film for fresh produce.

Acute ST-segment elevation myocardial infarction (ASTEMI) leads to great morbidity and mortality, even after immediate reperfusion therapy by primary percutaneous coronary intervention (PCI). Plasma exosomal proteins detected in the acute stage are supposed to affect the outcomes of ASTEMI. The present study collected ASTEMI patients with ischemic time around 6 hours and underwent successful emergency PCI, used exosomal proteomics to identify the plasma exosomal proteins, and performed a 1-year follow-up on ASTEMI outcomes. We observed that plasma exosomes concentration significantly decreased in ASTEMI after PCI than before it. Receiver operating characteristic (ROC) curve analysis revealed that several plasma exosomal proteins detected were strong predictors for coronary reintervention, which were revalidated in Cox regressions; while several plasma exosomal proteins were strong predictors for heart failure, which were revalidated in logistic regressions. The protein–protein network interactions and literature review suggest that plasma exosomal proteins might correlate with ASTEMI prognosis though involving in lipid and carbohydrate metabolism, regulation of cardiac muscle contraction, inflammation, platelet activation, or ferroptosis. Our results provide potential preventive and therapeutic targets for ASTEMI outcomes after PCI.

In the current study, we demonstrated that HRD1 was downregulated in TNBC tissues and dysregulated FAO by ubiquitinating CPT2, especially under glutamine‐deficient conditions. In addition, the curative effect of CB839 is more prominent in TNBC cells and tumors with high HRD1 expression. These findings provide insight into HRD1 as a regulator of lipid metabolism and have important implications for TNBC therapeutic targeting., Dependence on glutamine and acceleration of fatty acid oxidation (FAO) are both metabolic characteristics of triple‐negative breast cancer (TNBC). With the rapid growth of tumors, accelerated glutamine catabolism depletes local glutamine, resulting in glutamine deficiency. Studies have shown that the use of alternative energy sources, such as fatty acids, enables tumor cells to continue to proliferate rapidly in a glutamine‐deficient microenvironment. However, the detailed mechanisms behind this metabolic change are still unclear. Herein, we identified HRD1 as a regulatory protein for FAO that specifically inhibits TNBC cell proliferation under glutamine‐deficient conditions. Furthermore, we observed that HRD1 expression is significantly downregulated under glutamine deprivation and HRD1 directly ubiquitinates and stabilizes CPT2 through K48‐linked ubiquitination. In addition, the inhibition of CPT2 expression dramatically suppresses TNBC cell proliferation mediated by HRD1 knockdown in vitro and in vivo. Finally, we found that the glutaminase inhibitor CB839 significantly inhibited TNBC cell tumor growth, but not in the HRD1 knock‐downed TNBC cells. These findings provide an invaluable insight into HRD1 as a regulator of lipid metabolism and have important implications for TNBC therapeutic targeting.

West Nile virus (WNV) is an important neurotropic flavivirus that is widely distributed globally. WNV strain XJ11129 was first isolated in Xinjiang, China, and its genetic and biological characteristics remain largely unknown. In this study, phylogenetic and sequence analyses revealed that XJ11129 belongs to lineage 1a and shares high genetic identity with the highly pathogenic strain NY99. Then, the full-length genomic cDNA of XJ11129 was amplified and assembled using a modified Gibson assembly (GA) method. The virus (named rXJ11129) was successfully rescued in days following this method. Compared with other wild-type WNV isolates, rXJ11129 exhibited virulence indistinguishable from that of the NY99 strain in vivo. In summary, the genomic and virulence phenotypes of rXJ11129 were characterized in vivo and in vitro, and these data will improve the understanding of the spread and pathogenesis of this reemerging virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-020-00246-x) contains supplementary material, which is available to authorized users.

A recently modern stochastic optimization algorithm has been developed by observing the life of slime mold physarum polycephalum in nature. The algorithm is called the slime mold algorithm (SMA) with an excellent exploratory capacity and exploitation inclination. Still, slipping into optimal local is easy to happen and slowly converges speed while dealing with complicated problems. This article proposes a new process of improving SMA (namely ISMA) by adapting the weight coefficient and cooperating the reverse learning strategy in the expression of agents updating locations to enhance the algorithm’s optimization performance. Many selected benchmark functions and the optimal operation of cascade reservoirs are applied to evaluate the performance of the proposed algorithm. Comparisons of the proposed approach’s results with the various algorithms under the case situations show that the recommended solution produces better performance than the different competing algorithms.

Yellow fever virus (YFV) is a re-emerging flavivirus, which can lead to severe clinical manifestations and high mortality, with no specific antiviral therapies available. The live-attenuated yellow fever vaccine 17D (YF17D) has been widely used for over eighty years. However, the emergence of yellow fever vaccine-associated viscerotropic disease (YFL-AVD) and yellow fever vaccine-associated neurotropic disease (YFL-AND) raised non-negligible concerns. Additionally, the attenuation mechanism of YF17D is still unclear. Thus, the development of convenient models is crucial to understand the mechanisms behind YF17D attenuation and its adverse effects. In this work, we generated a reporter YF17D expressing nano-luciferase (NLuc). In vitro and in vivo characterization demonstrated that the NLuc-YF17D shared similar biological properties with its parental strain and the NLuc activity can reflect viral infectivity reliably. Combined with in vivo bioluminescence imaging, a series of mice models of YF17D infection was established, which will be useful for the evaluation of antiviral medicines and novel vaccine candidates. Especially, we demonstrated that intraperitoneally (i.p.) infection of NLuc-YF17D in type I interferon receptor-deficient mice A129 resulted in outcomes resembling YEL-AVD and YEL-AND, evidenced by viral replication in multiple organs and invasion of the central neuronal system. Finally, in vitro and in vivo assays based on this reporter virus were established to evaluate the antiviral activities of validated antiviral agents. In conclusion, the bioluminescent reporter virus described herein provides a powerful platform to study YF17D attenuation and vaccine-associated diseases as well as to develop novel countermeasures against YFV.

Adding some shapes to food in the production process can greatly increase the added value of food and make the same food. The market is more competitive. At present, cake decorating is mainly done manually, which requires high operating skills of personnel, and there are fewer optional decorating styles. Aiming at these shortcomings, a design concept of a smart cake spotting machine is proposed. This design uses a three-axis linkage device to cooperate with the cream delivery mechanism; the main control system used STM32F103ZET6 chip. It stores the G-code files of the flower pattern through the SD card and externally stores the SD card in the SD card data, external stepper motor drive circuit to control the operation of the mechanical structure. Finally, the stepper motor controls the displacement of the mechanism and conveys the cream. The movement of the mechanism makes it possible to finish the work of decorating the cake. In this article, the specific design and implementation of the cake automatic flowering machine are introduced in detail. This study has undergone experimental testing and the results show that the cake embossing machine designed by this study institute can automatically complete embossing according to the set embossing pattern.

This paper proposes a solution to the power grid system’s reactive power optimization scheduling problem (RPSP) based on a novel manta ray foraging optimization (MRFO) evolutionary algorithm. By applying the penalty function for the reactive power optimization model, the management of the constraints of the RPSP optimization formula is counting on for calculation. The experimental results of the proposed MRFO scheme are contrasted with other approaches for the IEEE-30 bus system, such as particle swarm optimization (PSO), grey wolf optimizer (GWO), moth-flame optimization algorithm (MFO), and whale optimization algorithm (WOA). Comparative results show that the MRFO algorithm can generate stable, strong convergence, high reliability effectively, and a feasible figuration needed space in solving optimization problems with reactive power optimization.

This paper suggests a solution for the image segmentation (IS) problem with the multilevel thresholding based on one of the latest hybrid swarm computation optimization algorithms, particle swarms, and gravitational search (PSGA). The experimental results are comparable with other state-of-the-art algorithms that show that the PSGA on selected images is better than the competitors.

A multi-objective paradigm arises a viable approach to solving complex problems of optimization based on integrating multiple disciplines. This paper sets forth a new multi-objective teaching–learning-based optimization (short for MTLBO) for the issue of automotive fuel consumption. The vehicle’s fuel consumption is related to the cost of traveling by gasoline and the current traffic conditions, e.g., congestion, roads. The least use of fuel and the shortest routes are modeled as the objective functions for candidates’ solutions on the automobile navigation route. A road transportation system is built based on wireless sensor network (WSN)-fitted sensor nodes and the car fitted with the global positioning system (GPS). The results of the simulation are contrasted with the approaches of the Dijkstra and the A* algorithm. Results from experiments show that the proposed method increases precision.

This study suggests a new metaheuristic algorithm for global optimization, based on parallel hybridizing the swarm optimization (PSO) and Gravitational search algorithm (GSA). Subgroups of the population are formed by dividing the swarm’s community. Communication between the subsets can be developed by adding strategies for the mutation. Twenty-three benchmark functions are used to test its performance to verify the feasibility of the proposed algorithm. Compared with the PSO, GSA, and parallel PSO (PPSO), the findings of the proposed algorithm reveal that the proposed PPSOGSA achieves higher precision than other competitor algorithms.

Mosquito-borne flaviviruses consist of a positive-sense genome RNA flanked by the untranslated regions (UTRs). There is a panel of highly complex RNA structures in the UTRs with critical functions. For instance, Xrn1-resistant RNAs (xrRNAs) halt Xrn1 digestion, leading to the production of subgenomic flaviviral RNA (sfRNA). Conserved short direct repeats (DRs), also known as conserved sequences (CS) and repeated conserved sequences (RCS), have been identified as being among the RNA elements locating downstream of xrRNAs, but their biological function remains unknown. In this study, we revealed that the specific DRs are involved in the production of specific sfRNAs in both mammalian and mosquito cells. Biochemical assays and structural remodeling demonstrate that the base pairings in the stem of these DRs control sfRNA formation by maintaining the binding affinity of the corresponding xrRNAs to Xrn1. On the basis of these findings, we propose that DRs functions like a bracket holding the Xrn1-xrRNA complex for sfRNA formation. IMPORTANCE Flaviviruses include many important human pathogens. The production of subgenomic flaviviral RNAs (sfRNAs) is important for viral pathogenicity as a common feature of flaviviruses. sfRNAs are formed through the incomplete degradation of viral genomic RNA by the cytoplasmic 5ʹ–3ʹ exoribonuclease Xrn1 halted at the Xrn1-resistant RNA (xrRNA) structures within the 3ʹ-UTR. The 3ʹ-UTRs of the flavivirus genome also contain distinct short direct repeats (DRs), such as RCS3, CS3, RCS2, and CS2. However, the biological functions of these ancient primary DR sequences remain largely unknown. Here, we found that DR sequences are involved in sfRNA formation and viral virulence and provide novel targets for the rational design of live attenuated flavivirus vaccine.

To calculate the required strength of a cemented backfill with high aspect ratio, the confirmation of lateral pressure is fundamental and needs to be determined first. As for the backfill with a high aspect ratio of height to length, the shape of the slip surface is not straight when in the active state due to the limited space, which is different from the general backfill. For this reason, a formulation of the slip surface with a curved shape and a lateral pressure calculation method based on this curved slip surface were proposed. The proposed equation of the slip surface is affected by the geometry parameters of the backfill, internal friction angle of the backfill, and the friction angle of the backfill-rock interface. Then, by the combination of the minor principal stress trajectory method and the horizontal slice method, an ordinary differential equation of stresses was established and then solved numerically. Finally, the method based on Mitchell’s three-dimensional limit equilibrium model was used to calculate the required strength of the cemented backfill. The calculated results were compared with previous studies and validated with numerical models. The results showed good consistency for the backfills with high aspect ratios.

Background Although a variety of antidiabetic drugs have significant protective action on the cardiovascular system, it is still unclear which antidiabetic drugs can improve ventricular remodeling and fundamentally delay the process of heart failure. The purpose of this network meta-analysis is to compare the efficacy of sodium glucose cotransporter type 2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, metformin (MET), sulfonylurea (SU) and thiazolidinediones (TZDs) in improving left ventricular (LV) remodeling in patients with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). Methods We searched articles published before October 18, 2019, regardless of language or data, in 4 electronic databases: PubMed, EMBASE, Cochrane Library and Web of Science. We included randomized controlled trials in this network meta-analysis, as well as a small number of cohort studies. The differences in the mean changes in left ventricular echocardiographic parameters between the treatment group and control group were evaluated. Results The difference in the mean change in LV ejection fraction (LVEF) between GLP-1 agonists and placebo in treatment effect was greater than zero (MD = 2.04% [0.64%, 3.43%]); similar results were observed for the difference in the mean change in LV end-diastolic diameter (LVEDD) between SGLT-2 inhibitors and placebo (MD = − 3.3 mm [5.31, − 5.29]), the difference in the mean change in LV end-systolic volume (LVESV) between GLP-1 agonists and placebo (MD = − 4.39 ml [− 8.09, − 0.7]); the difference in the mean change in E/e′ between GLP-1 agonists and placebo (MD = − 1.05[− 1.78, − 0.32]); and the difference in the mean change in E/e′ between SGLT-2 inhibitors and placebo (MD = − 1.91[− 3.39, − 0.43]). Conclusions GLP-1 agonists are more significantly associated with improved LVEF, LVESV and E/e′, SGLT-2 inhibitors are more significantly associated with improved LVEDD and E/e′, and DPP-4 inhibitors are more strongly associated with a negative impact on LV end-diastolic volume (LVEDV) than are placebos. SGLT-2 inhibitors are superior to other drugs in pairwise comparisons.

Zika virus (ZIKV) has evolved from an overlooked mosquito-borne flavivirus into a global health threat due to its astonishing causal link to microcephaly and other disorders. ZIKV has been shown to infect neuronal progenitor cells of the fetal mouse brain, which is comparable to the first-trimester human fetal brain, and result in microcephaly. However, whether there are different effects between the contemporary ZIKV strain and its ancestral strain in the neonatal mouse brain, which is comparable with the second-trimester human fetal brain, is unclear. Here we adopted a mouse model which enables us to study the postnatal effect of ZIKV infection. We show that even 100 pfu of ZIKV can replicate and infect neurons and oligodendrocytes in most parts of the brain. Compared with the ancestral strain from Cambodia (CAM/2010), infection of the ZIKV strain from Venezuela (VEN/2016) leads to much more severe microcephaly, accompanied by more neuronal cell death, abolishment of oligodendrocyte development, and a more dramatic immune response. The serious brain damage caused by VEN/2016 infection would be helpful to elucidate why the American strain resulted in severe neurovirulence in infants and will provide clinical guidance for the diagnosis and treatment of infection by different ZIKV strains., Highlights • The infection of an American strain of ZIKV leads to more severe microcephaly than the ancestral Asian strain. • American strain infects more cells, and induces more dramatic immune response and cell death than ancestral Asian strain. World attention has been drawn to a global Zika virus (ZIKV) outbreak due to its unexpected causal link to congenital brain abnormalities, especially microcephaly. Infection of pregnant women with the American Zika strain, but not the ancestral Asian strain, can result in microcephaly in infants. However, the phenotypic difference between the contemporary American strain and ancestral Asian strain of ZIKV is still unclear. We employed the ZIKV infection model of a neonatal mouse brain to compare the difference between these two strains. We find that infection by the American strain leads to more severe microcephaly than the ancestral Asian strain.

Active packages of shiitake mushrooms with CO 2 - and moisture-absorbing sachet or pad were designed and tested in their effectiveness in quality preservation for a given shelf life of 5 days at 10 °C. Sachets of sodium carbonate (SC) and mix of SC and calcium hydroxide (CH), and SC-impregnated cotton pad were characterized in their CO 2 and moisture absorption properties to calculate proper amounts of the active components capable of scavenging the required amounts of CO 2 and water vapour. The demands of CO 2 and water vapour absorptions to maintain the desired modified atmosphere (MA) and avoid moisture condensation inside the packages were determined from mass balance relationships comprising the mushroom respiration/transpiration and gas transmission through the package layer. Super-absorbent polymer (SAP) of polyacrylate was added as a supplement material to bring about the water vapour absorption required further to attain non-saturated humidity condition. Sachet combined of SC and SAP attached inside the package of 180 g mushrooms maintained its atmosphere of 10.7–11.6% O 2 and 7.1–8.9% CO 2 concentrations at steady state helping to preserve the quality best. Proper combination of CO 2 and moisture absorbers can be useful tool to create the desired MA and alleviate saturated humidity conditions in packages of the commodities sensitive to high CO 2 and moisture condensation.

Agar-based films with multiple functions (CO2 absorption, water vapor absorption, and antimicrobial activity) were developed, tested for their properties, and then applied to the packaging of fresh shiitake mushrooms as an insert label. The films were cast from an agar-based aqueous solution containing a dissolving plasticizer (glycerol), a CO2 absorbent (sodium carbonate [SC] alone or a combination of SC and sodium glycinate [SC-SG]), and a volatile antimicrobial agent (carvacrol [CRV]). The agar of the film matrix is designed to serve as a water vapor absorbent. The multifunctional films tended to have poor mechanical properties, with a hard texture and an opaque and yellowish color. The CO2 absorbent, either SC alone or SC-SG, affected CRV retention and release along with the CO2 and water vapor absorption behavior. Both films (SC-CRV and SC-SG-CRV films) showed good inhibitory effects against Pseudomonas fluorescens and Saccharomyces cerevisiae. SC-CRV film had a higher and faster CO2 absorpt...

Milk powder products as fatty dry foods are generally sensitive to moisture-adsorption, caking and oxidative deterioration. It is desirable that products with a water activity below 0.5 and a package of oxygen concentration below 2% are kept at storage temperatures below 25 °C for quality preservation and extended shelf life. Oxygen-excluded packages are usually used with barriers against ingress of water vapor and oxygen. A light barrier is another element for protecting against oxidation. Typical packages are metal cans, multilayer barrier pouches and composite cans. Additional attributes are also added onto the packaging to satisfy other needs such as convenience and communication depending on the product. Time temperature indictors showing real-time secondary shelf life are a recent development. While both nitrogen and carbon dioxide are employed for oxygen-excluded packages to prevent oxidation, carbon dioxide dissolvable in the product serves a role to control or reduce the pressure of rigid packages at proper gas mixture under distribution environment. Innovative preservative packaging technologies such as tailored modified atmosphere packaging and active packaging can be adopted to retain milk powder quality and extend the shelf life with additional benefits and effectiveness. Fast and persistent oxygen and moisture scavenging and antioxidant packaging have also been used.

Duck Tembusu virus (DTMUV), a newly identified flavivirus, has rapidly spread to China, Malaysia and Thailand. The potential threats to public health have been well-highlighted; however its virulence and pathogenesis remain largely unknown. Here, by using reverse genetics, a recombinant chimeric DTMUV based on Japanese encephalitis live vaccine strain SA14-14-2 was obtained by substituting the corresponding prM and E genes (named ChinDTMUV). In vitro characterization demonstrated that ChinDTMUV replicated efficiently in mammalian cells with small-plaque phenotype in comparison with its parental viruses. Mouse tests showed ChinDTMUV exhibited avirulent phenotype in terms of neuroinvasiveness, while it retained neurovirulence from its parental virus DTMUV. Furthermore, immunization with ChinDTMUV was evidenced to elicit robust IgG and neutralizing antibody responses in mice. Overall, we successfully developed a viable chimeric DTMUV, and these results provide a useful platform for further investigation of the pathogenesis of DTMUV and development of a live attenuated DTMUV vaccine candidate.