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The existing work is dedicated toward the manufacture of ZA-27/TiC as composites material via powder metallurgy. A mixture of Zn and Al with 63 and 27 wt%, respectively, is ball milled for 4 hrs at 145 rpm. Then, samples with disk-like shapes were made through pressing under 600 MPa and afterward sintered at 336 °C for 90 minutes in an electric furnace in argon gas. Other three groups from the above Zn and Al mixture ratio were prepared but with the addition of 3, 6, and 9 wt% TiC particles independently. The group's samples were prepared at the same conditions above. Hardness, density, and porosity microstructure observations, including optical and SEM-Mapping techniques were utilized to validate the effect of TiC particle additions with the listed above contents on the prepared ZA-27 alloy properties. The practical density of the prepared ZA-27 alloy is decreased basically owing to the used powder metallurgy route and with a lesser degree due to TiC addition. In contrast, the porosity is increased. But the hardness of the ZA-27 alloy is improved when TiC was added, and it was increased from 49.4 to 66 VHN with 0 to 9 wt% TiC addition. The optical microscope and SENM-Mapping facilities explained the distribution of co-existing Zn, Al, and TiC particles in the microstructures of the tested samples to improve the properties of ZA alloy.

In this paper, the results of our research were presented into the sliding wear behaviors of reinforced epoxy composites made with 3D networked carbon fibers ornamented with nanowires of cobalt oxides (NWRs@CFs). Composites are made using the cast-in-place method. Under different normal loads and sliding velocities, these composites' wear and friction coefficient performances are assessed. Tests were performed at 400 rpm spindle speed, 10, 20, and 30 N normal load, and a duration of 300 seconds. Pure epoxy exhibits wear rates of 0.449, 0.481, and 0.501 * 10-5 mm3/Nm at 10, 20, and 30N. Conversely, 3D CFs/epoxy composites exhibit lower wear rates (0.334, 0.360, and 0.390 * 10-5 mm3/Nm) at the same pressure. The epoxy composites of NWRs@CFs wear less, measuring 2.1, 3.5, and 0.4 * 10-5 mm3/Nm under applied loads. The effects of speed on the tribological characteristics were also studied, the friction coefficients for 400, 800, and 600 rpm at 10 N. Pure Epoxy has fraction coefficients of 0.449, 0.494, and 0.552µ at 400, 800, and 600 rpm. In comparison, three-dimensional carbon fibers and epoxy composites show reduced wear rates (0.334, 0.376, and 0.304 µ) under identical loads. Epoxy composites of NWRs@CFs have friction coefficients of 0.261, 0.304, and 0.332µ. Pure epoxy has high wear, indicating less friction resistance.

In most situations, predicting wear requires a variety of microstructural characterizations and experiments with contact surfaces. Based on physical principles, mathematical models might be of great assistance in understanding and thereby predicting this event. Considering the significance of heat generation in war, it appears that the parameters of thermodynamics are appropriate measurements for wear modelling. Entropy is among these parameters of thermodynamics. The Miedema model is a good method to predict the Gibbs free energy and entropy of solid solutions of binary and ternary systems. In this study, the wear behaviour of iron-based alloys according to their estimating values of Gibbs free energies and entropy was studied under lubricated conditions. The wear test was performed in accordance with ASTM-G99, utilizing the vertical universal friction testing machine MMW-1A and the pin-on-disk test methodology. Results show that the lowest negative value of Gibbs free energy was noted in the Fe-Al-Sn ternary system (-14.37 KJ/mol), while the highest negative value was found in the Fe-Al-V (-25.16 KJ/mol) binary system. It was also concluded that the wear rate decreased when the entropy estimate increased. The higher value of the wear rate was (6.935 mm3\N.m x107) for Fe-Al binary alloy with an entropy value (1.717 J\k Mole). The lowest value of wear rate was (3.581 mm3\N.m *107) for Fe-Al-Sn ternary alloy with an entropy of (2.71 J\k Mole). This is due to the micro-distortion that was mechanically indicated with the ternary alloys Fe-Al with V, Mn, Ga.B, and Sn additives that affected the wear mechanism and caused high values of wear.

Background: The clinical epidemiology of hospitalized COVID-19 patients has never been described before in Lebanon. Moreover, the hospital admission and PCR positivity rates have not been assessed and compared yet. Objectives: To describe the characteristics and outcomes of hospitalized patients with coronavirus induced disease 2019 (COVID-19) in Lebanon and identify risk factors for severe disease or death. Study design: This is a retrospective mono-center cohort study in which we used patients’ files to extract and analyse data on demographic and clinical characteristics, as well as mortality. Moreover, we tracked the pandemic by recording the daily total and ICU inpatient census and the PCR positivity rate for admitted and outpatients. Results: Although the total admission rate increased from September to April, the ICU census switched this trend in December to stabilize at an average of around 10 patients/day until April. The case fatality rate was 19% for the 902 hospitalized patients, of which the majority (80%) had severe COVID-19. The severity odds ratio is significantly decreased in immunosuppressed cases (OR, 0.18; CI, 0.05-0.67; p=0.011). Additionally, the odds of COVID-19 related death are significantly greater if consolidations are found in the chest computed tomography (CT) scan (OR, 12; CI, 2.63-55.08; p=0.0013). Conclusion: Consolidations in the lungs significantly increase the COVID-19 death risk. Risk factors identification is important to improve patients’ management and vaccination strategies. In addition, hospital statistics are good indicators of a pandemic's track.

The using of powders with attractive wear and friction has increased attention industrial sectors and research. In this study the experimental work results of the tribological behavior of base oil SN500 with CuO and ZrO2 as anti-wear and anti-friction hybrid additives powders at concentrations (0.5, 1, 2 and 4) wt. % were obtained and comparing the results with pure oil. Therefore the effect of normal loads and sliding speed under mixed lubrication were studied according to ASTM G-99 pin on disc and ASTM G-77 block on ring principles for friction and wear measurements respectively. The optimum lubrication concluded on the level of concentration of the hybrid powder was at (2) wt. % by the formation of protected boundary layer in the significantly improved i.e. friction coefficient decreased about (20.8%) and the wear rate about (46%) as compared with the case of using pure lubricant oil

The immunosuppression required for graft tolerance in kidney transplant patients can trigger latent BK polyomavirus (BKPyV) reactivation, and the infection can progress to nephropathy and graft rejection. It has been suggested that pre-transplantation BKPyV serostatus in donors and recipients is a predictive marker for post-transplantation BKPyV replication. The fact that research laboratories have used many different assay techniques to determine BKPyV serostatus complicates these data analysis. Even studies based on the same technique differed in their standard controls choice, the antigenic structure type used for detection, and the cut-off for seropositivity. Here, we review the different BKPyV VP1 antigens types used for detection and consider the various BKPyV serostatus assay techniques’ advantages and disadvantages. Lastly, we highlight the obstacles in the implementation of a consensual BKPyV serologic assay in clinics (e.g., the guidelines absence in this field).

Objectives. Hollow space between implant and abutment may act as reservoir for commensal and/or pathogenic bacteria representing a potential source of tissue inflammation. Microbial colonization of the interfacial gap may ultimately lead to infection and bone resorption. Using Rhodamine B, a sensitive fluorescent tracer dye, we aim in this study to investigate leakage at implant-abutment connection of three implant systems having the same prosthetic interface. Materials and Methods. Twenty-one implants (seven Astra Tech, seven Euroteknika, and seven Dentium) with the same prosthetic interface were connected to their original abutments, according to the manufacturers’ recommendation. After determination of the inner volume of each implant systems, the kinetic quantification of leakage was evaluated for each group using Rhodamine B (10−2 M). For each group, spectrophotometric analysis was performed to detect leakage with a fluorescence spectrophotometer at 1 h (T0) and 48 h (T1) of incubation time at room temperature. Results. Astra Tech had the highest inner volume (6.8 μL), compared to Dentium (4 μL) and Euroteknika (2.9 μL). At T0 and T1, respectively, the leakage volume and percentage of each system were as follows: Astra Tech 0.043 μL or 1.48% (SD 0.0022), 0.08 μL or 5.56% (SD 0.0074), Euroteknika 0.09 μL or 6.93% (SD 0.0913), 0.21 μL or 20.55% (SD 0.0035), and Dentium 0.07 μL or 4.6% (SD 0.0029), 0.12 μL or 10.47% (SD 0.0072). Conclusion. The tested internal conical implant-abutment connections appear to be unable to prevent leakage. In average, Astra Tech implants showed the highest inner volume and the least leakage.

Monoterpene indole alkaloids (MIAs) make up a highly bioactive class of metabolites produced by a range of tropical and subtropical plants. The corynanthe-type MIAs are a stereochemically complex subclass with therapeutic potential against a large number of indications including cancer, psychotic disorders, and erectile dysfunction. Here, we report yeast-based cell factories capable of de novo production of corynanthe-type MIAs rauwolscine, yohimbine, tetrahydroalstonine, and corynanthine. From this, we demonstrate regioselective biosynthesis of 4 fluorinated derivatives of these compounds and de novo biosynthesis of 7-chlororauwolscine by coexpression of a halogenase with the biosynthetic pathway. Finally, we capitalize on the ability of these cell factories to produce derivatives of these bioactive scaffolds to establish a proof-of-principle drug discovery pipeline in which the corynanthe-type MIAs are screened for bioactivity on human drug targets, expressed in yeast. In doing so, we identify antagonistic and agonistic behavior against the human adrenergic G protein-coupled receptors ADRA2A and ADRA2B, and the serotonergic receptor 5HT4b, respectively. This study thus demonstrates a proto-drug discovery pipeline for bioactive plant-inspired small molecules based on one-pot biocatalysis of natural and new-to-nature corynanthe-type MIAs in yeast.

Synthetic biology dictates the data-driven engineering of biocatalysis, cellular functions, and organism behavior. Integral to synthetic biology is the aspiration to efficiently find, access, interoperate, and reuse high-quality data on genotype-phenotype relationships of native and engineered biosystems under FAIR principles, and from this facilitate forward-engineering strategies. However, biology is complex at the regulatory level, and noisy at the operational level, thus necessitating systematic and diligent data handling at all levels of the design, build, and test phases in order to maximize learning in the iterative design-build-test-learn engineering cycle. To enable user-friendly simulation, organization, and guidance for the engineering of biosystems, we have developed an open-source python-based computer-aided design and analysis platform operating under a literate programming user-interface hosted on Github. The platform is called teemi and is fully compliant with FAIR principles. In this study we apply teemi for i) designing and simulating bioengineering, ii) integrating and analyzing multivariate datasets, and iii) machine-learning for predictive engineering of metabolic pathway designs for production of a key precursor to medicinal alkaloids in yeast. The teemi platform is publicly available at PyPi and GitHub., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: M.K.J., L.G.H. J.D.K. and J.Z. are inventors on pending patent applications. M.K.J., L.G.H., J.D.K., and J.Z. have financial interest in Biomia Aps. J.D.K. also has a financial interest in Amyris, Lygos, Demetrix, Napigen, Apertor Pharmaceuticals, Maple Bio, Ansa Biotechnologies, Berkeley Yeast, and Zero Acre Farms. The remaining authors declare no competing interests., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Monoterpenoid indole alkaloids (MIAs) represent a large class of plant natural products with marketed pharmaceutical activities against a wide range of indications, including cancer, malaria and hypertension. Halogenated MIAs have shown improved pharmaceutical properties; however, synthesis of new-to-nature halogenated MIAs remains a challenge. Here we demonstrate a platform for de novo biosynthesis of two MIAs, serpentine and alstonine, in baker's yeast Saccharomyces cerevisiae and deploy it to systematically explore the biocatalytic potential of refactored MIA pathways for the production of halogenated MIAs. From this, we demonstrate conversion of individual haloindole derivatives to a total of 19 different new-to-nature haloserpentine and haloalstonine analogs. Furthermore, by process optimization and heterologous expression of a modified halogenase in the microbial MIA platform, we document de novo halogenation and biosynthesis of chloroalstonine. Together, this study highlights a microbial platform for enzymatic exploration and production of complex natural and new-to-nature MIAs with therapeutic potential., (© 2023. The Author(s).)

Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including the essential anti-cancer therapeutics vinblastine and vincristine 1 . As MIAs are difficult to chemically synthesize, the world's supply chain for vinblastine relies on low-yielding extraction and purification of the precursors vindoline and catharanthine from the plant Catharanthus roseus, which is then followed by simple in vitro chemical coupling and reduction to form vinblastine at an industrial scale 2,3 . Here, we demonstrate the de novo microbial biosynthesis of vindoline and catharanthine using a highly engineered yeast, and in vitro chemical coupling to vinblastine. The study showcases a very long biosynthetic pathway refactored into a microbial cell factory, including 30 enzymatic steps beyond the yeast native metabolites geranyl pyrophosphate and tryptophan to catharanthine and vindoline. In total, 56 genetic edits were performed, including expression of 34 heterologous genes from plants, as well as deletions, knock-downs and overexpression of ten yeast genes to improve precursor supplies towards de novo production of catharanthine and vindoline, from which semisynthesis to vinblastine occurs. As the vinblastine pathway is one of the longest MIA biosynthetic pathways, this study positions yeast as a scalable platform to produce more than 3,000 natural MIAs and a virtually infinite number of new-to-nature analogues., (© 2022. The Author(s).)

Recent reports of antiepileptic activity of the fungal alkaloid TMC-120B have renewed the interest in this natural product. Previous total syntheses of TMC-120B comprise many steps and have low overall yields (11-17 steps, 1.5-2.9% yield). Thus, to access this compound more efficiently, we herein present a concise and significantly improved total synthesis of the natural product. Our short synthesis relies on two key cyclization steps to assemble the central scaffold: isoquinoline formation via an ethynyl-imino cyclization and an intramolecular Friedel-Crafts reaction to form the furanone.

New infectious diseases and increase in drug-resistant microbial pathogens emphasize the need for antibiotics with novel mode-of-action. Tetramates represented by fungi-derived tenuazonic acid and bacterial polycyclic tetramate macrolactams (PTMs) are an important family of natural products with a broad spectrum of antimicrobial activities. Despite their potential application as new antibiotics, it remains unknown how PTMs function. In this study, genomic mining revealed that PTM biosynthetic gene clusters (BGCs) are widespread in both Gram-positive and Gram-negative bacteria, and we investigated a sponge endosymbiont Actinoalloteichus hymeniacidonis harboring a potential PTM-BGC. Xanthobaccin A that previously has only been isolated from a Gram-negative bacterium was obtained after a scale-up fermentation, isolation, and structure elucidation through mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. Xanthobaccin A as well as two previously reported tetramates, equisetin and ikarugamycin, exhibited antibacterial activities against Bacillus subtilis . In addition, these three tetramates were for the first time to be confirmed as metallophores and the stoichiometry of the complexes were shown to be Fe(III)(equisetin) 3 /Fe(III)(equisetin) 2 and Fe(III)(ikarugamycin) 2 , respectively. Meanwhile, we found that all three tetramates could reduce ferric into ferrous iron, which triggers the Fenton chemistry reaction. Their antibacterial activity was reduced by adding the radical scavenger, vitamin C. Altogether, our work demonstrates that equisetin and PTMs can act as metallophores and their antimicrobial mechanism is possibly mediated through Fenton chemistry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ding, Zhang, Haidar, Bajimaya, Guo, Larsen and Gram.)

Background: Newcastle disease virus (NDV) is the causative agent of the Newcastle disease, a severe disease in birds associated with substantial economic losses to the poultry industry worldwide. Sweden is situated along the Western European waterfowl flyway and applies a non-vaccination policy combined with directives of immediate euthanisation of NDV infected flocks. During the last decades there have been several outbreaks with NDV in poultry in Sweden. However, less is known about the virus prevalence in the wild bird population including waterfowl, a well-established reservoir of avian paramyxovirus type 1 (APMV-1), the paramyxovirus serotype that include pathogenic NDV., Methods: The survey constituted of 2332 samples from Mallards (Anas platyrhynchos), trapped in the southern part of Sweden during autumn migration in 2010. These samples were screened for APMV-1 by real-time reverse transcription PCR, and viral strains from positive samples were isolated and characterized by sequence analysis of the fusion gene and by phylogenetic analysis., Conclusions: Twenty of these samples were positive for APMV-1, hence a virus prevalence of 0.9% (95% Confidence Interval [95% CI]=0.54%, 1.35%). The highest APMV-1 prevalence was detected in juvenile Mallards sampled in November (n=887, prevalence 1.24% ([95% CI])=0.67%, 2.24%). Sequence analysis and evaluation of phylogenetic relatedness indicated that isolated APMV-1 strains were lentogenic, and phylogenetically most closely related to genotype Ib strains within the clade of class II viruses. The sampling system employed enabled us to follow APMV-1 infections and the shedding of one particular viral strain in one individual bird over several days. Furthermore, combining previous screening results with the APMV-1 detections in this study showed that more than 50% of Mallards that tested positive for APMV-1 RNA were co-infected with influenza A virus.