Dietary polyphenols exist in two forms; extractable polyphenols (EPP) or compounds solubilised by aqueous/organic solvents, and non-extractable polyphenols (NEPP) or compounds remain in the corresponding residues after the extraction. At present, most researchers focus on EEP fractions, while NEPP is neglected. Thus, this study aimed to release NEPP from the remaining powder residue of Barhi date palm kernels (BDPK) with acid hydrolysis. The related extraction conditions were determined and optimised using response surface methodology (RSM) for maximisation of NEPP with highest cytotoxic and antioxidant activities. The face-centred central composite design (FCCCD) was used to establish treatments based on three independent variables, namely; extraction temperature, time, and solvent/sample ratio. Under the optimal conditions, the experimental values for DPPH radical-scavenging capacity of NEPP (IC50=57.52µg/mL), and cytotoxicity of NEPP against A549 and HT29 cells were IC50=17.4 µg/mL and 31.4µg/mL, respectively. The experimental values were in agreement with those predicted by RSM models, confirming the suitability of the model employed and the success of RSM for optimisation of the extraction conditions for NEPP from BDPK. These results indicate that NEPP from industrial date fruit waste could be a promising candidate as natural antioxidants with significant antiproliferation effect against A549 and HT29 cancer cells in-vitro.

The article describes facile one-pot, hi-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamide (3a–m) and carbohydrazide analogues (5a–l) as potential antifungal and antimicrobial agents. The structural integrity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compound 5h, 5i and 5j were found to be the most potent against A. fumigatus, with MIC value of 0.031 mg/mL. The compound 5f bearing a 2,6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking to the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron related deleterious side effects observed with existing antifungal compounds.

Fourteen (14) rack-mounted polycrystalline modules installed on the concrete roof of the solar energy applications laboratory at the Kwame Nkrumah University of Science and Technology (KNUST) in Ghana, a hot humid environment were assessed after 19 years of continuous outdoor expodure. The physical state of the modules was documented using a visual inspection checklist. They were further assessed by current-voltage (I-V) characterization and thermal imaging. The modules were found to be in good physical state, except some bubbles on front side and minor discolouration/corrosion at edge of the cells. Compared with reference values, the performance decline of the modules observed over the exposure period was: nominal power (P_nom), 21% to 35%; short circuit current (I_sc), 5.8% to 11.7%; open circuit voltage (V_oc) 3.6% to 5.6% and 11.9% to 25.7% for fill factor (FF). It is hoped that this study will provide some helpful information to project developers, manufacturers and the research community on the long-term performance of PV modules in Ghana.

Rice has become the second major food among rural people. It is one of the most nutrient and low-cost food available in Asia. Rice is composed of two major subspecies as Japonica and Indica and it belongs to the Poaceae family. The World Bank predicts that rice demand will grow 51% faster than population growth in 2025. It is high time to develop a model which predicts the type of infected paddy leaf and avoids the loss of grains. In this paper, the proposed hybrid CNN model, three CNN networks with different layer properties are trained parallel. The extracted feature from these CNN networks is combined to provide the classification of the type of infected leaf. Fieldwork was carried and about 340 samples are collected from five different types of classes. The proposed hybrid model was tested with both the fieldwork dataset and also with an available dataset on the internet. The experimental results show that the proposed model outperforms the other CNN network and yields an accuracy value of 98%, a precision value of 95%, and a misclassification rate of 4% respectively.

The Internet of Medical Things (IoMT) represents a specialized domain within the Internet of Things, focusing on medical devices that require regulatory approval to ensure patient safety. Trusted composition of IoMT systems aims to ensure high assurance of the entire composed system, despite potential variability in the assurance levels of individual components. Achieving this trustworthiness in IoMT systems, especially when using less-assured, commercial, off-the-shelf networks like Ethernet and WiFi, presents a significant challenge. To address this challenge, this paper advocates a systematic approach that leverages the Architecture Analysis & Design Language (AADL) along with Behavior Language for Embedded Systems with Software (BLESS) specification and behavior. This approach aims to provide high assurance on critical components through formal verification, while using less-assured components in a manner that maintains overall system determinism and reliability. A clinical case study involving an automated opioid infusion monitoring IoMT system is presented to illustrate the application of the proposed approach. Through this case study, the effectiveness of the systemic approach in achieving trusted composition of heterogeneous medical devices over less-assured networks is demonstrated.

Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the development of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.

Salmonella causes various type of disease worldwide with a remarkable pace. Salmonella enteric serotype typhi (S. typhi), a gram-negative bacterium (only cause disease in man) is the mainly causative agent of Typhoid fever. Typhoid fever is most common in poor and unprivileged developing countries of Asia and Africa. One of the major components of virulence factors produced during salmonella infection is Lipid A, which acts as a potent human immuno-modulator bacterial endotoxin. Regulation of Lipid A biosynthetic pathway occurs at second step, catalyzed by LpxC, a Zn2+ dependent metalloamidase. Systematic Screening of a pool of drug datasets like natural products library from Zinc database, Asinex database, Thiophene analogues fruitfully provided us 3 potent lead molecules s1_dl_mseq2, s1_ll_mseq2, and s2_ll_mseq8 which actively binds with LpxC enzyme and could be developed into sound inhibitors of LpxC enzyme after the application of drug development and processing strategies. Wet lab experimentation is required to validate these results for further use.

Natural Fibre Composites (NFC) are eco-friendly, sustainable alternatives to synthetic polymers. However, some intrinsic natural fillers´ properties hinder their widespread implementation as re-inforcement in polymeric matrices and require further investigation. In the scope of this study, the thermal, rheologic, mechanical (tension and flexural modes), morphological properties, water ab-sorption and dimensional stability of the NF polypropylene (PP) based injection moulded compo-sites with the rice husk (rh) and olive pits (op) of 20 wt% and 30% wt%, were investigated. The results suggest that the higher content of the rice husk and olive pits led to a similar reduction of the Melt Flow Index (MFI), independent of the additive type compared to virgin polypropylene (PPv). The melting and crystallization temperatures of the PPrh and PPop composites did not change with statistical significance. The composites are stiffer than the PP matrix by up to 49% and possess higher mechanical strength in what concerns the tension mode at the expense of de-creased ductility. PPrh and PPop have superior flexural modulus in the bending mode, while the flexural strength improvement was accomplished for the PP30%rh. The dimensional stability of the composites was improved as the linear shrinkage in the flow direction was decreased by 49% for PPrh and 30% for PPop, positively correlating with an increase in the filler content and stiff-ness. PPop was less susceptible to water sorption than PPrh due to fibres' composition and larger surface-to-area volume ratios.

Bottlebrush (BB) elastomers with water-soluble side chains and tissue-mimetic mechanical properties are promising for biomedical applications like tissue implants and drug depots. This work investigates the microstructure and phase transitions of BB elastomers with crystallizable polyethylene oxide (PEO) side chains by real-time synchrotron X-ray scattering. In the melt, the elastomers exhibit the characteristic BB peak corresponding to the backbone-to-backbone correlation. Upon crystallization of the side chains, the intensity of the peak decays linearly with crystallinity, and eventually vanishes due to BB packing disordering within intercrystalline amorphous gaps. This behavior of the bottlebrush peak differs from an earlier study of BBs with poly(ε-caprolactone) side chains, explained by stronger backbone confinement in the case of PEO, a high-crystallinity polymer. Microstructural models based on 1D SAXS correlation function analysis suggest crystalline lamellae of PEO side chains separated by amorphous gaps of monolayer-like BB backbones.

Marine macroalgae have garnered significant attention in the field of cosmeceutical research due to their rich abundance of bioactive compounds. These compounds offer remarkable skin benefits without inducing any adverse effects on human health, such as cytotoxicity, reproductive toxicity, genotoxicity, mutagenicity, or carcinogenicity. Among the various bioactive compounds found in brown algae, phenolic compounds exhibit diverse chemical structures and are present in high concentrations. In addition to phenolic compounds, brown algae also contain terpenoids, bro-mophenols, mycosporine amino acids (MAAs), and flavonoids, with the well-studied poly-phenol compound, phlorotannin, being particularly prominent. Marine macroalgae further possess an array of pigments derived from their natural pigmentation, including chlorophylls, carotenoids (such as fucoxanthin and β-carotene), phycobiliproteins (such as phycoerythrin and phycocyanin), and melanin. These pigments have been extensively investigated for their potential cos-meceutical applications. The phenolic compounds and pigments derived from marine macroalgae have been thoroughly studied for their beneficial effects on the skin, including skin whitening, moisturizing, photoprotection, anti-aging, anti-wrinkle, anti-melanogenic, and anti-oxidant properties. This comprehensive review aims to explore the extraction, characterization, and skin cosmetic effects of phenolic compounds and pigments derived from marine macroalgae, as documented in the existing literature, thereby enhancing our understanding of their therapeutic potential.

Objectives: To examine the long term impact of COVID-19 on sleep patterns and development of sleep disorders. Methods: Using the centralized Massachusetts General Brigham (MGB) Research Patient Data Registry (RPDR), SARS-CoV2 positive patients were surveyed about their sleep patterns before and after the viral infection. Information related to co-morbid conditions and medications were obtained through chart review. Results: Two hundred and forty five completed surverys were analysed. Average age was 53.3 ± 16.3 years, and participants were predominantly Non-Hispanic White (84.1%) and female (74.3%). Average BMI (kg/m2) was 29.9 ± 6.9, and a greater proportion was non-smokers (63.2%). After COVID-19, there was an increase in the percentage of participants reporting difficulty initiating (31 ± 46% vs. 39 ± 49%, P=0.01), and maintaining sleep (43 ± 49% vs. 57 ± 49%, P<0.001), and use of sleep aids (24 ± 43% vs. 30 ± 45% P=0.003) with an incidence rate of 24.3%, 37.4%, and 12.3% respectively. In addition, there was an increase in daytime fatigue and the need for napping (58 ± 49% vs. 36 ± 48%, P <0.0001) with an incidence of 8% and 23% respectively. The sleep symptoms persisted beyond 12 months among 28% of the participants and were predominantly seen among women. Conclusions: Infection with SARS-CoV2 has negative effects on sleep, and a significant proportion of adults experience insomnia and daytime sleepiness beyond 12 months after recovering from the initial infection.

The adoption of recycling and proper disposal techniques for electronic waste is crucial in advancing sustainable development. The traditional approaches of motivating people for collection of electronic waste are often insufficient due to inadequate methods reaching out, given incentives, calculating appropriate incentives associate to the task of gathering the electronic waste and a lack of transparency in the entire process. Insufficient collection of electronic waste could result in the release of numerous harmful substances into the environment. Prior research studies have been carried out to tackle the issue of electronic waste management in a broad sense. The findings of those studies indicated diverse strategies, each of which is relevant solely to a restricted range of electronic waste reprocessing circumstances. The current study has presented a proposed technique for incentivizing tasks and activities associated to collection of electronic waste through the adoption of vector space technique. Blockchain smart contact technology, has been used to implemented the strategy. The method used involves various well defined mapping of tasks, nature of activities, and their magnitude in order to derived an incentive. Some scenarios for the calculations of incentives are presented, and the findings reveals the based case is by utilizing weighting scale scheme where each tasks and activities are mapped to its associated inventive rather than providing fixed incentive values. Ethereum was used as digital token for each unit of incentive. This concept has contributed in encouraging personal accountability in the management of e-waste collection in order to cultivate sustainable behaviors for a long term solution.

This paper attempts to develop a Dynamic Mode Decomposition (DMD) based Reduced Order Model (ROMs) which can quickly but accurately predict the forces and moments experienced by a road vehicle such that they be used by an on-board controller to determine the vehicle's trajectory. DMD can linearize a large dataset of high-dimensional measurements by decomposing them into low-dimensional coherent structures and associated time-dynamics. This ROM then also can be applied to predict the future state of the fluid flow. Existing literature on DMD is limited to low Reynolds number applications. This paper presents DMD analyses of the flow around an idealized road vehicle, called the Ahmed body, at a Reynolds number of 2.7E6. The high dimensional dataset used in this paper was collected from a computational fluid dynamics (CFD) simulation performed using Menter's shear stress transport (SST) turbulence model within the context of Improved Delayed Detached Eddy Simulations (IDDES). The DMD algorithm, as available in literature, was found to suffer nonphysical dampening of the medium-to-high frequency modes. Enhancements to the existing algorithm were explored, and a modified DMD approach is presented in this paper which includes: (a) a requirement of higher sampling rate to obtain higher resolution of data, and (b) a custom filtration process to remove spurious modes. The modified DMD algorithm thus developed was applied to the high Reynolds number, separation dominated flow past the idealized ground vehicle. The effectiveness of the modified algorithm was tested by comparing future predictions of force and moment coefficients as predicted by the DMD-based ROM to the reference CFD simulation data, and found to offer significant improvement.

Self-healing ceramic composites are promising smart materials for high-temperature applications. To better understand their behaviors under service conditions, numerous studies have been performed both experimentally and numerically, and kinetics parameters such as activation energy and frequency factor are reported to be indispensable for investigating healing phenomena. Here, we propose a method for determining the kinetic parameters of self-healing ceramic composites based on the oxidation kinetics model of strength recovery. These parameters are determined by an optimization method using experimental strength recovery data under various healing temperatures and times and microstructural features on the fractured surfaces. Alumina and mullite matrix-based self-healing ceramic composites, such as Al2O3/SiC, Al2O3/TiC, Al2O3/Ti2AlC (MAX phase), and mullite/SiC, were selected as target materials. The theoretical strength recovery behaviors of the cracked specimens obtained from the determined kinetic parameters were compared with the experimental results. The determined parameters are within the previously reported range, and the predicted strength recovery behaviors are reasonably agreed with the experimental values. The proposed method can also be applied to other self-healing ceramics with matrices reinforced with different healing agents to evaluate oxidation rate, crack healing rate, and theoretical strength recovery behaviors for designing self-healing materials used in high temperature applications. Furthermore, the healing ability of composites can be fairly discussed regardless of the type of strength recovery test.

The Direction-of-Arrival (DoA) estimation methods are highly versatile and find extensive applications in satellite communication. The DoA methods are employed across a range of orbits, from Low Earth Orbits (LEO) to Geostationary Earth Orbits (GEO). They serve multiple applications, including altitude determination, geolocation and estimation accuracy, target localization, and relative and collaborative positioning. This paper presents a novel approach for modeling the DoA angle using a closed-form expression, incorporating the boresight angle and satellite and Earth station position data. The method uses the geographic coordinate system in the satellite communication system, precisely the latitude and longitude of the Earth station and altitude parameters of the satellite stations, to calculate the Earth station’s elevation angle and accurately model the DoA angle. Furthermore, this paper performs a comprehensive comparative analysis of various DoA methods to gain deeper insights into the performance of DoA estimation in multi-antenna systems operating under spatially correlated channels. Accordingly, this paper evaluates DoA estimation performance using root-mean-square-error (RMSE) statistics for uplink and downlink conditions through extensive Monte Carlo simulations. The simulation’s effectiveness is validated against the Cramer-Rao Bound (CRB) performance metric for the Additive white Gaussian noise (AWGN) case. (i.e., thermal noise). The simulation results demonstrate improved RMSE performance in satellite systems by incorporating spatial correlation into the system model.

Information about molecular mechanism of pesticide resistance in the rust-red flour beetle, a major pest destroying grains and flour across Nigeria is grossly lacking, hindering evidence-based con-trol. Here, we identified to species level three populations of the red-flour beetle from Kano, Ni-geria, as Tribolium castaneum, and investigated the mechanism driving their insecticide resistance. IRAC susceptibility bioassays established high cypermethrin resistance, with LC50s of 4.35-5.46mg/ml in the three populations, NNFM, R/Zaki and Yankaba. High DDT and malathion resistance was observed in NNFM, with LC50s of 15.32- and 3.71mg/ml, respectively. High sus-ceptibility was observed towards dichlorvos in all three populations with LC50s of 0.17-0.35mg/ml, respectively. Synergist bioassay with piperonylbutoxide significantly restored cypermethrin sus-ceptibility, with mortality increasing almost threefold, from 24.8% obtained from 1.25mg/ml of cypermethrin, to 63.3% in synergised group (p=0.013), suggesting a preeminent role of P450s. The two major knockdown resistance (kdr) mutations, T929I and L1014F in the IIS4 and IIS6 fragments of voltage-gated sodium channel were not detected in both cypermethrin-alive and cyperme-thrin-dead beetles, suggesting lesser role of target-site insensitivity. These findings highlight the need to explore alternative control tools for this pest and/or explore incorporation of synergists, like piperonylbutoxide as additional chemistries into pesticides formulations to improve their ef-ficacy.

In this paper we propose a computational framework that merges mechanistic modeling with deep neural networks obeying the Systems Biology Markup Language (SBML) standard. Over the last 20 years, the systems biology community has developed a large number of mechanistic models in SBML that are currently stored in public databases. With the proposed framework, existing SBML mechanistic models may be upgraded to hybrid systems through the incorporation of deep neural networks into the model core, using a freely available python tool. The so-formed hybrid mechanistic/neural network models are trained with a deep learning algorithm based on the adaptive moment estimation method (ADAM), stochastic regularization and semidirect sensitivity equations. The trained hybrid models are encoded in SBML and stored back in model databases, where they can be further analyzed as regular SBML models. The application of this approach is illustrated with three well-known case studies: the threonine synthesis model in Escherichia coli, the P58IPK signal transduction model, and the Yeast glycolytic oscillations model. The proposed framework is expected to greatly facilitate the widespread use of hybrid modeling techniques for systems biology applications.

As exemplified by the global response to the SARS-CoV-2 pandemic, whole genome sequencing played an important role in monitoring the evolution of novel viral variants and provided guidance on potential antiviral treatments. The recent rapid and extensive introduction and spread of highly pathogenic avian influenza virus in Europe, North America and elsewhere raises the need for similarly rapid sequencing to aid in appropriate response and mitigation activities. To facilitate this objective, we investigated a next generation sequencing platform that uses a portable nanopore sequencing device to generate and present data in real time. This platform offers the potential to extend in-house sequencing capacities to laboratories that may otherwise lack resources to adopt sequencing technologies requiring large benchtop instruments. We evaluated this platform for routine use in a diagnostic laboratory. In this study we evaluated different primer sets for the whole genome amplification of influenza A virus and evaluated five different library preparation approaches for sequencing on the nanopore platform using the MinION flow-cell. A limited amplification procedure and a rapid procedure were found to be best among the approaches taken.

Cold gas dynamic spray (CS) is a unique technique to deposit material using high strain rate solid state deformation. A major challenge for this technique is its dependence on the powder properties and lack of standards to assess them between lots and manufacturers. The motivation of this research was to understand the variability in powder atomization techniques for stainless steel powders and their subsequent properties for their corresponding impact on CS. A drastic difference (~30%) was observed in deposition efficiencies (DE) of unaltered, spherical, and similar sized stainless steel (316) powders produced using centrifugal (C.A) and traditional gas atomization (G.A) techniques. The study highlights more on differences on precursor level. Using recent advancements in large scale statistical measurements like laser diffraction shape analysis, µCT scanning, traditional methods like EBSD, nano-indentation, an attempt is made to understand the powder property. Insights on powder size and shape are documented. Significant differences were observed between C.A and G.A powders in terms of grain size, fraction of higher angle grain boundaries (HAGB) and nano hardness. The outcomes of this study would be helpful to understand the commercialization of the cold-spray process for bulk manufacturing of powder precursors

Sensing Technology (ST) plays a key role in Structural Health Monitoring (SHM) systems. ST focuses on developing sensors, sensory systems or smart materials that monitor a wide variety of materials properties aiming to create smart structures and smart materials, using Embedded Sensors (ESs), and allowing continuous and permanent measurements of the structural integrity. The integration of ESs is limited to the processing technology to embed the sensor due to its high-temperature sensitivity and the possibility of damage during its insertion into the structure. In addition, the technological process selection is dependent on the base material composition, either metallic or composite parts. The selection of smart sensors or the technology underlying them is fundamental to the monitoring mode. This paper presents a critical review of the fundaments and applications of sensing technologies for SHM employing ESs, focusing on the actual developments and innovation of these, as well as analysing the challenges that these technologies present, to build a path that allows a connected world through distributed measurement systems.

Steam boiler has a significant role in the industrial sector. The failure in boiler tubes significantly reduces the availability of the plant. Furthermore, deposits on the inner tube wall contribute to such failure by changing the thermal resistance of the wall, which causes a significant increase in the tube wall's temperature and, consequently, lower allowable stress. The presented thermal-fluid model is developed for the water tube. The model is implemented using ANSYS FLUENT to estimate the wall maximum water tube wall temperature considering the deposits layer and then determine the minimum thickness of the tube wall via ASME standards to assure safe operation. The model is verified via a mesh independence test. The minimum tube thickness is recommended and justified given the thermo-mechanical performance of the water tubes at several operating loads of 50, 75, and 100 %. These loads are implemented by different convective heat transfer coefficients of flue gases under different deposit thicknesses, thermal conductivity, and flue gas temperature. The present work contributes to the literature by recommending the minimum thickness of the water wall tubes and highlighting the thermo-mechanical effect of the deposits on water tube resilience under different operating conditions.

Organically-coated nanomaterials are intensively studied and find numerous applications in a wide range of areas ranging from optics to biomedicine. One of the recent trends in material science is the application of bio-mimetic polydopamine coatings that can be produced on a variety of substrates in a cost-efficient way under mild conditions. Such coatings not only modify the biocompatibility of the material but also add functional amino groups to the surface that can be further modified by classic conjugation techniques. Here we show an alternative strategy of substrates modification using not dopamine but dopamine conjugates. Compared to the classic scheme the proposed strategy allows for separation of the "organic" and "colloidal" stages and simplifies identification and purification steps. Modification with pre-modified dopamine allowed to achieve high active components loading up to 10.5% wt. A series of organo-inorganic hybrids were synthesized and their bioactivity was analyzed.

Frequency combs (FCs)—spectra containing equidistant coherent peaks—have enabled researchers and engineers to measure the frequencies of complex signals with high precision thereby revolutionising the areas of sensing, metrology and communications and also benefiting the fundamental science. Although mostly optical FCs have found widespread applications thus far, in general FCs can be generated using waves other than light. Here, we review and summarise recent achievements in the emergent field of acoustic frequency combs (AFCs) including phononic FCs and relevant acousto-optical, Brillouin light scattering and Faraday wave-based techniques that have enabled the development of phonon lasers, quantum computers and advanced vibration sensors. In particular, our discussion is centred around potential applications of AFCs in precision measurements in various physical, chemical and biological systems in conditions, where using light, and hence optical FCs, faces technical and fundamental limitations, which is, for example, the case in underwater distance measurements and biomedical imaging applications. This review article will also be of interest to readers seeking a discussion of specific theoretical aspects of different classes of AFCs. To that end, we support the mainstream discussion by the results of our original analysis and numerical simulations that can be used to design the spectra of AFCs generated using oscillations of gas bubbles in liquids, vibrations of liquid drops and plasmonic enhancement of Brillouin light scattering in metal nanostructures. We also discuss the application of non-toxic room-temperature liquid-metal alloys in the field of AFC generation.

Parts produced by laser or electron-beam powder bed fusion (PBF) additive manufacturing are prone to residual stresses, deformations, and other defects linked to non-uniform temperature distribution during the manufacturing process. Several researchers have highlighted the important role scan sequence plays in achieving uniform temperature distribution in PBF. However, scan sequence continues to be determined offline based on trial-and-error or heuristics, which are neither optimal nor generalizable. To address these weaknesses, we have articulated a vision for an intelligent online scan sequence optimization approach to achieve uniform temperature distribution, hence reduced residual stresses and deformations, in PBF using physics-based and data-driven thermal models. This paper proposes SmartScan, our first attempt towards achieving our vision using a simplified physics-based thermal model. The conduction and convection dynamics of a single layer of the PBF process are modeled using the finite difference method and radial basis functions. Using the model, the next best feature (e.g., stripe or island) that minimizes a thermal uniformity metric is found using control theory. Simulations and experiments involving laser marking of a stainless steel plate are used to demonstrate the effectiveness of SmartScan in comparison to existing heuristic scan sequences for stripe and island scan patterns. In experiments, SmartScan yields up to 43% improvement in average thermal uniformity and 47% reduction in deformations (i.e., warpage) compared to existing heuristic approaches. It is also shown to be robust, and computationally efficient enough for online implementation.

Here we studied Bianchi type-III string cosmological models generated by means of a cloud of strings with particles connected to them in the framework of Lyra geometry considering five-dimensional space-time. To obtain the exact solutions of field equations we consider that the shear scalar and the scalar expansion are proportional, σ∞θ which leads to D=cn and secondly we adopt the assumption considering the Reddy String Condition, ρ+λ=0. From the two different cases obtained here, first case leads to the Bianchi type-III string cosmological model in Lyra geometry in five-dimensional space-time and the second case leads to the five-dimensional vacuum universe in general relativity. The Geometrical and physical properties of the model universe are studied comparing with the present day’s observational findings. The model universe obtained here starts with the big bang and as time progresses both particle density ρp and energy density ρ decreases with expansion of our Universe.

Aedes albopictus is an invasive mosquito species responsible for local transmission of chikungunya and dengue viruses in Europe. In the absence of available treatments, insecticides-based control is one of the most important viable strategies to prevent emerging problems. Diflubenzuron (DFB) and Bacillus thuringiensis var. israelensis (Bti) are among the most commonly used larvicides for Ae. albopictus control which pose major concerns for potential resistance development. Studies on the resistance emergence of Ae. albopictus to both DFB and Bti and its persistence in the wild are essential for the efficient and sustainable planning of the control programs. In this concept, larvae from a recently laboratory established population were subjected to increasing selective pressure for nine successive generations against both DFB and Bti. At the end of this process, the resistance levels and the overwintering success of the selected populations relative to control (colonies that received no selection) were determined. Results revealed a substantial and a moderate increase on the resistance levels following selection with DFB and Bti respectively. Interestingly, the selection process to both larvicides had no apparent impacts on the overwintering capability relative to control suggesting the successful persistence of the resistant individuals in the wild from year to year.

Bioethanol has many environmental and practical benefits as a transportation fuel. It is one of the best alternatives to replace fossil fuels due to its liquid nature which is similar to petrol and diesel fuels traditionally used in transportation. In addition, bioethanol production technology has the capacity for negative carbon emissions which is vital for solving the current global warming dilemma. However, conventional bioethanol production takes place based on an inland site and relies on freshwater and edible crops (or land suitable for edible crop production) for production, which has led to the food vs fuel debate. Establishing a coastal marine biorefinery (CMB) system for bioethanol production that is based on coastal sites and relies on marine resources (seawater, marine biomass and marine yeast) could be the ultimate solution. In this paper, we aim to evaluate the environmental impact of using seawater for bioethanol production at coastal locations as a step towards the evaluation of a CMB system. Hence, a life cycle assessment for bioethanol production was conducted using the proposed scenario named Coastal-Seawater and compared to the conventional scenario, named Inland-Freshwater (IF). The impact of each scenario in relation to climate change, water depletion, land use and fossil depletion was studied for comparison. The coastal-seawater scenario demonstrated an improvement upon the conventional scenario in all the selected impact categories. In particular, the use of seawater in the process had a significant effect on water depletion showing an impact reduction of 31.2%. Furthermore, reductions are demonstrated in natural land transformation, climate change and fossil depletion of 5.5%, 3.5% and 4.2% respectively. This indicates the positive impact of using seawater and coastal locations for bioethanol production and encourages research to investigate the CMB system.

Pancreatic cancer is the third leading cause of cancer-related deaths in the United States. Pancreatic ductal adenocarcinoma (PDA) is the most common (90%) and aggressive type of pancreatic cancer. Genomic analyses of PDA specimens have identified the recurrent genetic mutations that drive PDA initiation and progression. However, the underlying mechanisms that further drive PDA metastasis remain elusive. Despite many attempts, no recurrent genetic mutation driving PDA metastasis has been found, suggesting that PDA metastasis is driven by epigenetic fluctuations rather than genetic factors. Therefore, establishing epigenetic mechanisms of PDA metastasis would facilitate the development of successful therapeutic interventions. In this review, we provide a comprehensive overview on the role of epigenetic mechanisms in PDA as a critical contributor on PDA progression and metastasis. In particular, we explore the recent advancements elucidating the role of nucleosome remodeling, histone modification, and DNA methylation in the process of cancer metastasis.

The severe disease outbreak COVID-19 pandemic impacted public health and safety and the educational systems worldwide. For fear of the further spread of diseases, most educational institutions, including Bangladesh, have postponed their face-to-face teaching. Therefore, this study explores public university student's perceptions towards online classes during the COVID-19 pandemic in Bangladesh. Data were collected among students of Islamic University, Kushtia, Bangladesh, through an online survey. The study followed both a qualitative and quantitative approach, where the survey technique was used as an instrument of data collection. Results showed that most students were facing difficulty participating in virtual classes and could not communicate with their friends correctly during online classes. They faced challenges in online schooling, and the majority of the students preferred conventional types of learning to virtual classes and did not understand the content of virtual classes easily. The study also explored that most students did not feel comfortable in online classes. Still, considering the present pandemic situation, they decided to participate in online classes to continue schooling. Besides, the study discovered that female students showed better real perceptions than male students regarding online classes, and urban students have more optimistic appreciation than rural students. Moreover, laptop or personal computer users showed more positive perceptions towards online education than mobile users. Furthermore, Broadband/ Wi-Fi users have more positive perceptions than mobile network users. These findings would be an essential guideline for governments, policymakers, technology developers, and university authorities for making better policy choices in the future.

Colorectal cancer is a major threat to the society causing the death through metastasis to several patients with stage IV. Computational tools provide a relatively quick procedure in order to evaluate several molecules for their drug activity. Prenylated flavonoids are well known for their anticancer properties even in colon cancer. Here, we provided altered structures of chalcones, based on theoretical studies that are showing better binding affinities to several colon cancer related proteins. Using molecular docking and dynamics, alongside with density function theory and ADMET studies we are representing two new derivatives of Xanthohumol prenylated flavonoids having promising results against this disease.

This article aims to discuss, the stability and boundedness character of the solutions of the rational equation of the form \begin{equation}\label{eql21.1} y_{t+1}=\frac{\nu\epsilon^{-y_t}+\delta\epsilon^{-y_{t-1}}}{\mu+\nu y_t+\delta y_{t-1}},\quad t\in N(0). \end{equation} Here, $\epsilon>1, \nu,\delta,\mu\in (0,\infty)$ and $y_0, y_1$ are taken as arbitrary non-negative reals and $N(a)=\{a,a+1,a+2,\cdots \}$. Relevant examples are provided to validate our results. The exactness is tested using MATLAB.

Tissue engineering has the potential for repairing large bone defects, which impose a heavy financial burden on the public health. However, difficulties with O₂ delivery to the cells residing in the interior of tissue engineering scaffolds make it challenging to grow artificial tissues of clinically-relevant sizes. This study uses image-based simulation in order to provide insight into how to better optimize the scaffold manufacturing parameters, and the culturing conditions, in order to resolve the O₂ bottleneck. To do this, high resolution 3D X-ray images of two common scaffold types (salt leached foam and non-woven fiber mesh) are fed into a Lattice Boltzmann Method fluid dynamics and reactive Lagrangian Scalar Tracking mass transfer solvers. The obtained findings indicate that the scaffolds should have maximal surface area-to-solid volume ratios, for higher chances of the molecular collisions with the cells. Furthermore, the cell culture media should be flown through the scaffold pores as fast as practically possible (without detaching or killing the cells). Finally, we have provided a parametric sweep that maps how the molecular transport within the scaffolds is affected by variations in rates of O₂ consumption by the cells. Ultimately, the results of this study are expected to benefit the computer-assisted design of tissue engineering scaffolds and culturing experiments.

Appropriate estimation of soil settlement is of significant importance since it directly influences the performance of building and infrastructures that are built on soil. In particular, the settlement of fine-grained soils is critical because of low permeability and continuous settlement with time. Coefficient of consolidation (C_c) is a key parameter to estimate settlement of fine-grained soil layers. However, estimation of this parameter is time consuming, needs skilled technicians, and specific equipment. In this study, C_c was estimated using several soil parameters such as liquid limit (LL), plastic limit (PL), and initial void ratio (e₀). Estimating such parameters in laboratory is straight forward and needs substantially less time and cost compared to conventional tests to estimate C_c such as oedometer test. This study presents a novel prediction model for C_c of fine-grained soils using gene-expression programming (GEP). GEP is a biologically inspired technique capable of offering closed-form solution for the optimal solution. A database consisted of 108 different data points was used to develop the model. A closed-form equation solution was derived to estimate C_c based on LL, PL, and e₀. The performance of developed GEP-based model was evaluated through coefficient of determination (R²), root mean squared error (RMSE), and mean average error (MAE). High R² and low error values indicated the descent performance of the model. Furthermore, the model was evaluated using the additional performance measures and met all the suggested criteria. Furthermore, the model had a better performance in terms of R², RMSE, and MAE compared to most of existing models. It is expected that the developed model will decrease the time and cost associate with determining C_c of fine-grained soils.Keywords: evolutionary model, gene-expression programming (GEP), prediction, soil compression index, estimation, soil engineering, soil informatics, civil engineering, machine learning, data science, big data, soft computing, deep learning, forecasting, subject classification codes, construction informatics, computational intelligence (CI), artificial intelligence (AI), estimation

The myocardial extracellular matrix is not a passive entity, but rather a complex and dynamic microenvironment which represents an important structural and signaling system within the myocardium. Understanding the fundamental role of hypoxia and peroxidation in the genesis of many cardiovascular diseases has stimulated the development of strategies that can enhance the energy-producing functions of cells. Revealing the alterations in cardiac metabolism and function associated with sustained exposure to high altitude advances our understanding of hypoxia-related disease. The study was conducted on 26 adult males of Wistar rats weighing 220–310 g, divided into 3 groups. The first control group consisted of 6 intact animals, the second group included 10 rats which were exposed to hypobaric hypoxia without medication for 30 days. Third group was composed of 10 rats, which were medicated by succinic acid solution which was injected intraperitoneally once a day at the rate of 0.5 mL/100 g of animal body weight 15 minutes before hypoxic exposure for 30 days. Fibrosis in the myocardium inevitably leads to increased myocardial stiffness, resulting in systolic and diastolic dysfunction, neurohormonal activation and, ultimately, heart failure Changes in cardiac highenergy phosphate metabolism may underlie the myocardial dysfunction caused by hypobaric hypoxia. Reduced oxygen delivery by microvascular damage, increased perivascular fibrosis associated with reduced cellular oxygen availability may contribute to contractile failure. Succinic acid combined with inosine acts as a high-energy phosphate reserve, to maintain adenosine triphosphate at levels sufficient to support contractile function.

Recent evidence suggests the existence of shared neural resources for rhythm processing in language and music. Such overlaps could be the basis of the facilitating effect of regular musical rhythm on spoken word processing previously reported for typical children and adults, as well as adults with Parkinson’s disease and children with developmental language disorders. The present study builds upon these previous findings by examining whether musical rhythmic priming also influences visual word processing, and the extent to which such cross-modal priming effect of rhythm is related to individual differences in musical aptitude and reading skills. EEG was recorded while participants listened to a rhythmic tone prime, followed by a visual target word with a stress pattern that either matched or mismatched the rhythmic structure of the auditory prime. Participants were also administered standardized assessments of musical aptitude and reading achievement. ERPs elicited by target words with a mismatching stress pattern showed an increased fronto-central negativity. Additionally, the size of the negative effect correlated with individual differences in musical rhythm aptitude and reading comprehension skills. Results support the existence of shared neurocognitive resources for linguistic and musical rhythm processing, and have important implications for the use of rhythm-based activities for reading interventions.

Chitosan decorated copper nanoparticles (CS/CuNPs) catalysts were synthesized via reduction methods utilizing green protocol. The CS/CuNPs hybrid catalysts were tested for the synthesis of quinoline derivatives utilizing one-pot multicomponent reaction (MCR) under ultrasonic irradiation. The best catalyst (CS/CuNPs) that provided good conversion reaction yield and high turnover frequency (TOF) was characterized using Fourier transform infrared (FTIR), Thermogravimetric analyses (TGA), X-ray diffraction (XRD), , scanning electron microscopy (SEM), transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS) techniques. Generalization of the scope of the proposed catalytic process was studied using different aldehydes. Excellent products yield and high TOF in even shorter reaction time (~5 min) was attained. Recyclability performance of the catalyst over five times re-use without detectable loss in product yield was recorded. The current method is green process utilizing environmentally benign catalyst and considered to be promising sustainable protocol for the synthesis of fine chemicals.

In 2016 northern Nigeria experienced a devastating infestation by the tomato leaf miner, leading to soaring in prices of tomato across the country. Unfortunately, information on the bionomics and resistance status of this pest is lacking in northern Nigeria, hampering appropriate control measures. Here, we identified to species level, and using conventional and synergist bioassays characterised pesticides resistance profile of a field population of a tomato leaf miner from northern Nigeria. Highest resistance was obtained with λ-cyhalothrin (Type II pyrethroid) with a low mortality (18.52% at 56hr) and LD₅₀ of 7461.474ppm. Resistance was also established toward propoxur and chlorpyrifos-methyl with average mortalities each of 56% and LD_50s of 1023.51ppm and 106.351ppm, respectively. Highest susceptibility was seen with abamectin with mortality of 86% and LD₅₀ of 0.034ppm. Pre-exposure to piperonyl butoxide significantly recovered λ–cyhalothrin susceptibility (mortality = 90% and LD₅₀ = 0.92ppm) implicating the P450 monoxygenases in the resistance. No significant changes in mortalities were obtained on pre-exposure to diethyl maleate and triphenyl-phosphate- inhibitors of glutathione S-transferases and carboxylesterases, respectively. The finding of resistance to these agricultural pesticides will sensitize stakeholders across Nigeria to take action to manage the resistance at an early stage before it gets out of hand.

Following the detection of highly pathogenic avian influenza (HPAI) virus in countries bordering Kenya to the west, we conducted surveillance among domestic and wild birds along the shores of Lake Victoria. In addition, between 2018 and 2020, we conducted surveillance among poultry and poultry workers in live bird markets and among wild migratory birds in various lakes that are resting sites during migration to assess introduction and circulation of avian influenza viruses in these populations. We tested 7,464 specimens (oropharyngeal and cloacal swabs) from poultry and 6,531 fresh fecal specimens from wild birds for influenza A viruses by real-time RT-PCR. Influenza was detected in 3.9% (n=292) of specimens collected from poultry and 0.2% (n=10) of fecal specimens from wild birds. On hemagglutinin subtyping, most of the influenza A positives from poultry (274/292, 93.8%) were H9. Of 34 H9 specimens randomly selected for further subtyping, all were H9N2. On phylogenetic analysis, these viruses were genetically similar to other H9 viruses detected in East Africa. Only two of the ten influenza A positive specimens from the wild bird fecal specimens were successfully subtyped; sequencing analysis of one specimen collected in 2018 was identified as low pathogenicity avian influenza H5N2 virus of the Eurasian lineage and the second specimen, collected in 2020, was subtyped as H11. A total of 18 OP/NS swabs from poultry workers with ARI (12%) were collected; none were positive for influenza A virus. We observed significant circulation of H9N2 influenza viruses in poultry in live bird markets in Kenya. During the same period, low pathogenic H5N2 virus was detected in a fecal specimen collected in a site hosting a variety of migratory and resident birds. Although HPAI H5N8 was not detected in this survey, these results highlight the potential for introduction and establishment of highly pathogenic avian influenza viruses in poultry populations and the associated risk of spillover to human populations.

Diabetic cardiac autonomic neuropathy (DCAN) is a severe complication of type 1 diabetes mellitus (T1DM) characterized by autonomic nerve fiber dysfunction in the heart and blood vessels. This study aimed to elucidate the histopathological mechanisms underlying DCAN and evaluate the therapeutic potential of MCC950, an NLRP3 inflammasome inhibitor, in a Wistar rat model. Male Wistar rats were divided into control and T1DM groups, with diabetes induced by streptozotocin (STZ) injection. Following confirmation of DCAN through elevated serum noradrenaline levels, diabetic rats were subdivided into positive control (insulin-treated), treatment (MCC950), and untreated groups. The stellate ganglia, thoracic aorta, and left ventricle were dissected for histological examination using Haematoxylin and Eosin (H&E) and Masson Trichrome staining. STZ-induced hyperglycemia was evident by Week 2 and sustained throughout the study. Serum noradrenaline levels significantly increased by Week 14 in diabetic rats, indicating DCAN onset. Histological analysis revealed atrophy in stellate ganglia, endothelial damage in the thoracic aorta, and myocardial fibrosis in untreated diabetic rats. MCC950 treatment preserved ganglionic structure, mitigated vascular damage, and reduced myocardial fibrosis, demonstrating its potential in attenuating DCAN progression. These findings highlight MCC950 as a promising therapeutic agent for DCAN by targeting inflammation and preserving autonomic and cardiovascular function. Further investigations are warranted to validate MCC950’s efficacy in human trials, with the potential to improve clinical outcomes for T1DM patients at risk of DCAN.

The perovskite crystal structure has garnered significant attention due to its unique properties and potential applications. Particularly, YTiO3 is a ferromagnetic Mott insulator with strong electron correlation effects and orbital ordering, so it is a good candidate for electronic applications. In this research, we investigate the structural, elastic, and electronic properties of Y1-xSrxTiO3 (x=0.01, 0.10, 0.50, 0.99) perovskites within the Pm3m space group using density functional theory (DFT) to improve mechanical properties while preserving electronic properties. Initial geometry optimizations were performed using the GGA-PBE functional with a 6×6×6 Monkhorst-Pack k-point mesh. The study utilized the CASTEP code with ultrasoft pseudopotentials for DFT calculations. Complete structural relaxations were achieved, and the elastic constants which confirm the mechanical stability of the materials were determined using the finite strain theory. The electronic properties were analyzed through band structure and partial density of states (PDOS) calculations. Despite variations in band structures due to Sr doping, no bandgap was observed, indicating the metallic nature of the compounds. The study highlights that p and d orbitals are predominant in electronic states. The findings suggest that Sr doping significantly influences the elastic properties, making these materials potentially valuable for various applications requiring robust mechanical properties.

Some of neurodegenerative diseases may be characterized by continuing behavioral and cognitive dysfunction that contains memory loss and/or apathy. Alzheimer's disease is the most typical type of such neurodegenerative disease characterized by deficit of cognition and alteration of behavior. Despite the huge efforts against Alzheimer's disease, there has been yet no successful treatment for this disease. Interestingly, several possible risk genes to cognitive dysfunction are frequently expressed within brain cells, which may also be linked to cholesterol metabolism, lipid transport, exosomes and/or caveolae formation, suggesting that caveolae may be a therapeutic target to consider cognitive dysfunctions. Interestingly, modulation of autophagy/mitophagy with the alteration of glucagon-like peptide-1 (GLP-1) and N-methyl-d-aspartate (NMDA) receptors signaling may offer a novel approach to prevent and alleviate the cognitive dysfunction. A paradigm that both GLP-1 and NMDA receptors at caveolae sites is promising and crucial for the treatment of cognitive dysfunctions has been presented here, which might also be able to modify the progression of Alzheimer's disease. This research direction may open the potential to move a clinical care toward disease-modifying treatment strategies with maximal benefits for patients without detrimental adverse events for neurodegenerative diseases.

Liraglutide, a glucagon-like peptide 1 analog used to treat type 2 diabetes and obesity, is a po-tential new treatment modality for bile acid (BA) diarrhea. Here, we show that administration of liraglutide significantly decreased total BAs, especially the primary BAs, including cholic acid, chenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, glycocholic acid, and β-muricholic acid, in the liver and feces. In addition, liraglutide significantly decreased trypto-phan metabolites, including L-tryptophan, serotonin, 5-hydroxy indole-3-acetic acid, L-kynurenine, and xanthurenic acid, in the colon, whereas it significantly increased in-dole-3-propionic acid. Moreover, the administration of liraglutide remarkably decreased the ex-pression of apical sodium-dependent bile acid transporter, which mediates BA uptake across the apical brush border member in the ileum, ileal BA binding protein, and fibroblast growth factor 15 in association with decreased expression of the BA-activated nuclear receptor farnesoid X receptor and the heteromeric organic solute transporter Ostα/β, which induces BA excretion, in the ileum. Liraglutide acutely decreased body weight and blood glucose levels in association with decreases in plasma insulin and serotonin levels in food-deprived mice. These findings suggest the potential of liraglutide as a novel inhibitor of primary BAs and serotonin in the colon, which may be in-volved in the improvement of BA diarrhea.

Quaking aspen (Populus tremuloides Michx.) is an important deciduous species in western U.S. forests. Existing maps of aspen distribution are based on Landsat imagery and often miss small stands (&lt;0.09 ha or 30 m²), which rapidly regrow when managed or following disturbance. In this study, we present methods for deriving a new regional map of aspen forests using one year of Sentinel-1 (S1) and Sentinel-2 (S2) imagery in Google Earth Engine. We assessed the annual phenology of aspen in the Southern Rockies and leveraged the frequent temporal resolution of S1 and S2 to create ecologically relevant seasonal composites. Additionally, we derived spectral indices and radar textural features targeting the canopy structure, moisture, and chlorophyll content. Using spatial block cross-validation and Random Forests, we assessed the accuracy of different scenarios and selected the best performing set of features for classification. Comparisons were then made with existing landcover products across the study region. The resulting map improves on existing landcover products in both accuracy (average F1-score = 93.1%) and detection of smaller forest patches. These methods enable accurate mapping at spatial and temporal scales relevant to forest management for one of the most widely distributed tree species in North America.

Variance-driven decomposition based on the singular spectrum analysis of the European Project for Ice Coring in Antarctica (EPICA) dD, CO2 and CH4 records allowed a novel quantitative structural interpretation of all glacial/interglacial cycles and glacial terminations of the last 800 kyr. This bottom-up approach used the response components of EPICA stacked records to reconstruct the envelope of the thermal response through a physical interference model. The aim was to improve the understanding regarding the features of intensity, amplitude, and asymmetry of 73 marine isotope stages (MIS) and seven terminations. The Antarctic stack record can be described by a variance-weighted interference model of ten thermal waves of different origins (mid-term oscillation, orbitals and suborbitals) that stochastically interfere at a given time according to their relative differences in frequency, intensity, and polarity. Interglacial/glacial stages resulted from constructive interference and bipolar amplification of warming/cooling responses, respectively. The low intensity MISs (including 90% of substages) and the unbiased-dated terminations fell in the low interference regions where dominant destructive patterns minimise the thermal envelope. The positive skewness of the EPICA stack resulted from the constructive interference with a strong bias in the warming direction, especially after the Mid-Brunhes Event. Duration analysis of short eccentricity hemicycles exhibited an intrinsic unexpectedly prolonged mean cooling in the nominal solution (5.8 kyr) and its EPICA response as well (8.6 kyr), along with an interference-induced asymmetry (21.1 kyr). The overall effect resulted in the saw-tooth shape of glacial cycles which is heavily induced by interference and related to the intermediate feedback mechanisms controlled by short eccentricity.

Mutations of PKD1 coding for polycystin-1 (PC1) account for most of the autosomal dominant polycystic kidney disease (ADPKD). The extracellular region of PC1 contains many evolutionarily conserved domains for ligand interactions. Among these is the leucine-rich repeats (LRR) in the far N-terminus of PC1. Using zebrafish (Danio rerio) as an in vivo model system, we explored the role of LRR in the function of PC1. Zebrafish expresses two human PKD1 paralogs, pkd1a and pkd1b. Knockdown of both genes in zebrafish by morpholino antisense oligonucleotides produced phenotypes of dorsal axis curvature and pronephric cyst formation. We found that overexpression of LRR suppressed both phenotypes in pkd1-morphant zebrafish. Purified recombinant LRR domain inhibited proliferation of HEK cells in culture and interacted with the heterotrimeric basement membrane protein laminin-511 (α5β1γ1) in vitro. Mutations of amino acid residues in LRR structurally predicted to bind laminin-511 disrupted LRR-laminin interaction in vitro and neutralized the ability of LRR to inhibit cell proliferation and cystogenesis. Our data support the hypothesis that the extracellular region of PC1 plays a role in modulating PC1 interaction with the extracellular matrix and contributes to cystogenesis of PC1-deficiency.

Background: Breast cancer is a commonly diagnosed cancer worldwide. Human MutT homolog 1 (MTH1) is found to be elevated in breast tumors and cancer cells are addicted to MTH1 for sur-vival. Pharmacological inhibition of MTH1 may be potentially beneficial in the treatment of breast cancer. Methods: MA-24 was screened by malachite green colorimetric assay from MTH1 inhibitors and the kinetic characteristics of MA-24 was assessed. Binding features of MA-24 with MTH1 was as-certained through molecular docking, and cytotoxic activity of MA-24 was validated in vitro and in vivo. Target engagement assays, comet assay and western blot confirmed that the intracellular target and mechanism of MA-24. Results: MA-24 with potent antitumor bioactivity both in vitro and in vivo. MA-24 competitively inhibited the MTH1 and further induce DNA strand breaks, leading to increased apoptosis of cancer cells depending on upregulation of cleaved-caspase 3 – cleaved-PARP axis. Especially, MA-24 exhibited a powerful efficacy and safety in vivo (tumor growth inhibition rate: 61.8%). Conclusions: MA-24 possesses a broad spectrum of breast cancer cytotoxicity and offered valuable insights for overcoming the challenges of chemotherapy-related toxicity, which holds great po-tential for further development MA-24 as an anti-cancer drug.

Ipomoea batatas L. (IBL) has gained significant popularity as a complementary therapy or herbal medicine in the treatment of anti-diabetes. The objective of this review is to examine the mechanism of action of flavonoid compounds found in IBL that can activate GLP-1 as an anti-diabetic agent. The review article refers to PRISMA guidelines. The literature search was conducted using electronic databases such as Crossref, Pubmed, Scopus, and Science Direct. The search query was based on specific keywords, including Ipomoea batatas OR sweet potato AND anti-diabetic OR hypoglycemic. A total of 1055 articles were found, but only 32 articles were selected for further review based on inclusion and exclusion criteria. IBL contains various compounds, including phenolic acid, flavonols, flavanols, flavones, and anthocyanins, which exhibit activity against anti-diabetes. Flavonols, flavonols, and flavones belong to a group of flavonoids that possess the ability to form complexes with AlCl3 and Ca2+. Retention of Ca2+ within intracellular L cells, resulting in the release of GLP-1. Flavonols, flavones, and flavone groups have been found to strongly interact with DPP-IV, which inhibits the degradation of GLP-1. This mechanism effectively prolongs the half-life of GLP-1 in the systemic system, thereby contributing to the anti-diabetic activity of IBL

Objective: To analyze the relation between alterations in the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis during the first 6 months of life and weight in children born in the Lower Middle São Francisco region. Methods: This is an analytical cohort, with a quantitative approach and a translational perspective. Thirty children with low and normal birth weight were initially identified in a hospital and reapproached at 3 and 6 months of age. Birth weight and alterations in GH/IGF-1 curves at birth, third month, and sixth month of life. Results: Weight gain during the 6 months of follow-up in newborns with low birth weight was greater compared to newborns with normal birth weight. All children who were born with low birth weight had an altered GH/IGF-1 curve at birth (p = 0.002). Most newborns with low birth weight maintained the alteration in the GH/IGF-1 curve at the third month of life (p = 0.027). Regarding the GH/IGF-1 curve at the sixth month, alteration persisted in greater proportion among children with low birth weight. Conclusion: Alterations in insulin resistance markers, demonstrated by increased GH without a proportional increase in IGF-1, were observed to be significant in children with low birth weight, with greater adiposity in this group, which may increase the risk of metabolic diseases in later life.

Human pulmonary paragonimiasis, an emerging concern in North East India, frequently masquerades as pulmonary tuberculosis due to clinical and radiological similarities, leading to diagnostic challenges. This research was aimed to harness the immunoblotting technique to discern immunodiagnostic protein antigens from both adult worm and excretory-secretory (ES) extracts of the prevalent Paragonimus westermani type 1 in Arunachal Pradesh, North East India. We studied the time kinetics of immunoreactive patterns in relation to the duration of infection in rodent models. Immunoblot analyses were also conducted using sera from ELISA positive patients confirmed with paragonimiasis, facilitating the selection of antigenic extracts with diagnostic potential. Further, ES proteins antigens were subjected to 2D- immunoblot analysis and immunoreactive protein spots identified by MALDI-TOF MS. Immunoreactivity patterns of ES antigens with sera of paragonimiasis positive patients were detailed, and specific immunoreactive protein antigens were pinpointed using peptide mass fingerprinting (MALDI-TOF). This work underscores the enhanced diagnostic accuracy when combining ELISA with immunoblotting for pulmonary paragonimiasis in regions like North East India, marked by co-existing helminth infections.

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8+ T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C*03:02-restricted CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope exclusively restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies.

Type 1 diabetes is a chronic condition that results from the destruction of insulin-producing β-cells in the pancreas. Current treatments for type 1 diabetes, such as insulin therapy and pancreatic islet transplantation, have several limitations and, hence not quite effective in the long run. As current therapy methods fail to slow disease development, novel strategies such as the development of a bioartificial pancreas are being seriously considered. Over the last decade, research has focused on tissue engineering, which aids in the design of biological alternatives for the repair and replacement of non-functional or damaged organs. Three dimensional (3D) bioprinting technology which employs 3D printing technology to generate 3D tissue-like structures from biomaterials and cells, offers a promising solution for the treatment of type 1 diabetes by providing the ability to generate functional endocrine pancreatic tissue. Bioprinted structures are therefore an important aspect of tissue engineering because they have been found to replicate the native extracellular matrix, promoting cell survival and proliferation. In this review, we extensively discussed about bioprinting endocrine pancreas for the treatment of type 1 diabetes particularly focussing on the choice of cells, biomaterials, growth factors, and essential considerations. Additionally, the key challenges and perspectives towards recapitulation of the pancreatic function of the pancreatic organ engineering technologies have also been discussed.

Monitoring snowmelt dynamics in mountains is crucial to understand water releases downstream. Sentinel-1 (S-1) synthetic aperture radar (SAR) has become one of the most widely used techniques to achieve this aim due to its high frequency of acquisitions and all-weather capability. This work aims to understand the possibilities of S-1 SAR imagery to capture snowmelt dynamics and related changes in streamflow response in semiarid mountains. The results proved that S-1 SAR imagery was able not only to capture the final spring melting but also all melting cycles that commonly appear throughout the year in these types of environments. The general change detection approach to identify wet snow was adapted for these regions using as reference the average S-1 SAR image from the previous summer, and a threshold of -3.00 dB. In addition, four different type of melting runoff onsets depending on physical snow condition were identified. When translating that at the catchment scale, distributed melting runoff onset maps were defined to better understand the spatiotemporal evolution of melting dynamics. Finally, a linear connection between melting dynamics and streamflow was found for long-lasting melting cycles, with a determination coefficient (R2) ranging from 0.62 to 0.83 and an average delay between the melting onset and streamflow peak of about 21 days.

Powder metallurgy is a preferred manufacturing method in various industries because it offers design flexibility, material efficiency and a cost-effective production. In this work, we study the effects of different compaction directions on the strength of parts produced by powder metallurgy. Al–4wt.%Cu alloys are used due to their recyclability, and three distinctive compaction pressures are applied, resulting in two sample groups. One group is air-cooled after sintering, while the other is water-quenched and naturally aged (T4 temper). Both the compressive and tensile strengths are measured and analyzed. The study reveals that both heat treatments and compaction directions significantly influence anisotropic strengths. The novelty of this research lies in the use of powders that can be reused from machining, turning, or foundry rejection. By omitting or reducing the melting stage and employing simple powder metallurgy, the cost-effective and environmentally friendly processes are achieved. The planning of compaction load, compaction direction, and heat treatments is found to play a crucial role in determining the final mechanical performance. Notably, this approach aligns with the environmental, social and governance (ESG) practices that have been increasingly adopted by industry.

Prevention and management of cytomegalovirus (CMV) reactivation is important to improve outcome of allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The aim of this study was to analyze real-world data for incidence and characteristics of CMV infections until 1-year after allo-HCT under 100-day letermovir prophylaxis. A single-center retrospective study was conducted between November 2020 and October 2021. During the study period, 358 patients underwent allo-HCT, 306 of whom received letermovir prophylaxis. Cumulative incidence of clinically significant CMV infection (CS-CMVi) was 11.4%, 31.7%, and 36.9% at 14-weeks, 24-weeks, and 1-year post-HCT, respectively. In multivariate analysis, risk of CS-CMVi increased with graft-versus-host disease (GVHD) ≥ grade 2 (adjusted odds ratio 3.640 [2.036–6.510]; P &lt; 0.001). One-year non-relapse mortality was significantly higher in letermovir breakthrough CS-CMVi patients than those with subclinical CMV reactivation who continued letermovir (P = 0.002). There were 18 (15.9%) refractory CMV infection in this study population. In summary, letermovir prophylaxis is effective in preventing CS-CMVi until day 100, which increased after cessation of letermovir. GVHD is still a significant risk factor in letermovir prophylaxis era. Further research is needed to establish individualized management strategies especially in patients with significant GVHD or letermovir breakthrough CS-CMVi.

Glycated hemoglobin (HbA1c) is used to assess glycemic control in Type 1 diabetes (DM1) patients. Apolipoproteins play an essential role in DM1 pathophysiology and may be associated with complications, as well as HbA1c. This cross-sectional observational study consisting of 81 children and adolescents of both sexes diagnosed with DM1 investigated the relationship between body fat distribution and lean mass with HbA1C and apolipoprotein values analyzing biochemical and body composition measurements. Shapiro-Wilk test with Lilliefors correction, non-parametric Mann-Whitney test, and others were used with a significance level of 5%. The sample had a diagnosis time of 4.32 years and high blood glucose levels (mean 178.19 mg/dL) and HbA1c (mean 8.57%). Subjects also had a moderate level of adiposity, as indicated by arm and thigh fat areas. The study also found significant differences in the distribution of patients concerning levels of apolipoproteins A and B, with a smaller proportion of patients having undesirable levels. Finally, the study found a significant difference in the distribution of patients with estimated cardiovascular risk based on the ApoB/ApoA-1 ratio. Conclusively, visceral fat in children and adolescents with DM1 may increase the risk of DM1 long-term complications owing to its association with elevated HbA1C and apolipoprotein values.

A novel group of conjugative plasmids of Pseudomonas is characterized. The prototype plasmid pPPUT-Tik1-1 (153663 bp), isolated from a permafrost strain of P. putida Tik1, carries a defective mercury transposon Tn501 and a streptomycin resistance transposon Tn5393. Ten plasmids and 34 contigs with backbone regions closely related to pPPUT-Tik1-1 have been found in Gene Bank. Two of these plasmids isolated from clinical strains of P. putida and P. fulva are almost identical to the ancient plasmid. A characteristic feature of this group of plasmids is the presence of two genes encoding the initiators of replication (repA1 and repA2). None of these genes has high similarity with plasmid replication genes belonging to known incompatibility groups. It has been demonstrated that while pPPUT-Tik1-1-like plasmids have homologous backbone regions they significantly differ by the molecular structure and the functional burden of their accessory regions. Some of the pPPUT-Tik1-1-related plasmids carry determinants of antibiotic resistance and/or heavy metal salts. Some plasmids are characterized by the ability to degrade xenobiotics. Plasmids related to pPPUT-Tik1-1 are characterized by a narrow host range and are found in various species of Pseudomonas genus. A group of shortened plasmids containing the same replication module, but without conjugation genes, were also found. These plasmids also contain other structural changes that strongly distinguish them from plasmids related to pPPUT-Tik1-1. The data obtained indicate the need for a complex approach to the classification of plasmids.

Secretory and membrane proteins are vital for cell activities, including intra- and intercellular communication. Therefore, protein quality control in the endoplasmic reticulum (ER) is an essential and crucial process for eukaryotic cells. Endoplasmic reticulum-associated degradation (ERAD) targets misfolded proteins during the protein maturation process in the ER and leads to their disposal. This process maintains the ER productive function and prevents misfolded protein stress (i.e., ER stress). The ERAD-stimulating factor ER degradation-enhancing α mannosidase-like 1 protein (EDEM1) acts on misfolded proteins to accelerate ERAD, thereby maintaining the productivity of the ER. However, the detail mechanism underlying the function of EDEM1 in ERAD is not completely understood due to lack of established physiological substrate proteins. In this study, we attempted to identify substrate proteins for EDEM1 using siRNA. The matrix component thrombospondin-1 (TSP1) and epidermal growth factor receptor (EGFR) were identified as candidate targets of EDEM1. Their protein maturation status and cellular localization were markedly affected by knockdown of EDEM1. We also showed that EDEM1 physically associates with EGFR and enhances EGFR degradation via ERAD. Our data highlight the physiological role of EDEM1 in maintaining specific target proteins and provide a potential approach to the regulation of expression of clinically important proteins.

Type 1 Diabetes mellitus (T1DM) occurs when insulin is not produced in the Pancreas due to the autoimmune destruction of the beta cells. The patients may be diagnosed after 80-90% of the beta cells are destroyed. Insulin remains the essential medicine in T1DM management, under continuous monitoring of glucose levels. T1DM management consists of a complex and precise set of self-care measures for the entire life; during this continuous process, the patients could become overwhelmed, angry, anxious, frustrated, and/or discouraged. Therefore, to be widely used and provide general benefits, new technologies for DM management must provide clinical advantages without compromising safety. The compliance of T1DM patients is also essential, thus improving their quality of life (QoL). Moreover, the accessibility of the new system for patients through healthcare coverage is critical; they must be able to buy the new devices and accessories and pay for their maintenance. In this context, our work aims to describe the most recent technologies regarding continuous glucose monitors (CGMs) and continuous subcutaneous insulin infusion (CSII) systems, correlated with psychosocial impact and capacity to improve T1DM patients' life quality.

The reef manta ray (Mobula alfredi) is a highly mobile and plankton-feeding species, classified vulnerable to extinction on the IUCN Red List for Threatened Species. Knowledge on their spatial ecology and the extent of their dispersal remain incomplete, especially within island-fragmented habitats as found in New Caledonia. Satellite telemetry was used to investigate the horizontal movement ecology of reef manta rays in New Caledonia. A total of 21 manta rays were tagged with pop-up satellite archival transmitting tags (21 Fastloc and 2 MiniPAT) that remained deployed for a duration ranging from 3 to 180 days (mean ± SE = 76.7 ± 50.3). Rays presented a strong site fidelity and an important affinity for coastal waters. Long-distance migrations (> 300 km) were also observed, mainly through coastal and shallow water paths. Horizontal movements were compared to a home range area and classified into four distinct patterns: Fidelity, Excursion, Fidelity + Relocation and Relocation. The most dominant pattern was Fidelity where manta rays remained within their home range for the whole duration of the tag deployment. Our findings may assist the design of more appropriate management strategies for the species in New Caledonia and other regions worldwide.

Observations of ocean surface winds from Indian scatterometer SCATSAT-1 have been combined with background wind field from a numerical weather prediction (NWP) model available at National Centre for Medium Range Weather Prediction (NCMRWF) to generate a 6-hourly gridded hybrid wind product. A distinctive feature of the study is to produce a global gridded wind field from SCATSAT-1 scatterometer passes with spatio-temporal data gaps at regular synoptic hours relevant for forcing models and other NWP studies. This is done by making use of concepts from the modern particle filter technique, which does not represent the model probability density function (PDF) following the Gaussian technique. The 6 hourly hybrid wind is generated for the entire year of 2018 and is validated using the wind speed from daily gridded level-4 SCATSAT-1 winds (L4AW), Cross Calibrated Multi-Platform dataset (CCMP) and global buoy data from National Data Buoy Centre (NDBC). The results indicate potential of the technique to produce scatterometer winds at the desired temporal frequency with significantly less noise and along swath biases. The study shows the generated hybrid winds have very high quality with respect to the already existing daily product available from ISRO.

Feline panleukopenia (FPL), a highly contagious and frequently fatal disease of cats, is caused by Feline parvovirus (FPV) and Canine parvovirus (CPV). We characterized the diversity of these Carnivore protoparvovirus 1 variants in 18 faecal samples collected from domestic cats with FPL during an outbreak, using targeted parvoviral DNA metagenomics to a mean depth of >10,000 X coverage per site. All samples comprised FPV alone. Compared to the reference FPV genome, isolated in 1967, 44 mutations were detected. Ten of these were non-synonymous, including 9 in non-structural genes and one in VP1/VP2 (Val232Ile), which was the only one to exhibit inter-host diversity, being present in five sequences. There were five other polymorphic nucleotide positions, all with synonymous mutations. Intra-host diversity at all polymorphic positions was low with sub-consensus variant frequencies (SVF) of >1% except for two positions (2108 and 3208) in two samples with SVF of 1.1 – 1.3%. Intra-host nucleotide diversity was measured across the whole genome (0.7 - 1.5%) and for each gene, and was highest in the NS2 gene of four samples (1.2 – 1.9%). Overall, intra-host viral genetic diversity was limited and most mutations observed were synonymous, indicative of a low background mutation rate and strong selective constraints.

Aim: Sca-1+CD31− cells were shown to be endothelial stem/progenitor cells, found in many mammalian tissues, including heart, were able to differentiate into cardiomyocytes in vitro and in vivo. Our previous work indicated that heart derived Sca-1+CD31− cells increased Nr1d1 mRNA level and decreased cells plasticity with aging. However, little is known about how NR1D1 affects Sca-1+CD31− cells plasticity. Methods: Lentiviral vector was used to stably overexpress Nr1d1 in young Sca-1+CD31− cells and to knockdown Nr1d1 in aged Sca-1+CD31− cells. Cell differentiation, proliferation, apoptosis, and cell cycle were evaluated. Results and Conclusions: The overexpression of Nr1d1 in young Sca-1+CD31− cells inhibited cell proliferation and promoted apoptosis. Knockdown of Nr1d1 in aged Sca-1+CD31− cells promoted cell proliferation and inhib-ited apoptosis. Using mouse cardiac myocytes cell line, confirmed the effect of Nr1d1 and indi-cated that Nr1d1 induce Serpina3 expression via Nr1d1 interaction with Nr4a3. Nr1d1 may there-fore be identified as a potent anti-aging receptor and be a therapeutic target for aging relative diseases.

PSD-95 (Dlg4) is an ionotropic glutamate receptor scaffolding protein essential in synapse stability and neurotransmission. PSD-95 levels are reduced during aging and in neurodegenerative diseases like Huntington’s disease (HD), and it is believed to contribute to synaptic dysfunction and behavioral deficits. However, the mechanism responsible for PSD-95 dysregulation under these conditions is unknown. The Heat Shock transcription Factor 1 (HSF1), canonically known for its role in protein homeostasis, is also depleted in both aging and HD. Synaptic protein levels, including PSD-95, are influenced by alterations in HSF1 levels and activity, but the direct regulatory relationship between PSD-95 and HSF1 has yet to be determined. Here, we showed that HSF1 chronic or acute depletion in cell lines and mice decreased PSD-95 expression. Furthermore, HSF1(+/-) mice had reduced PSD-95 synaptic puncta that paralleled a loss in thalamo-striatal excitatory synapses, an important circuit disrupted early in HD. We demonstrated that HSF1 binds to regulatory elements present in the PSD-95 gene and directly regulates PSD-95 expression. HSF1 DNA-binding on the PSD-95 gene was disrupted in an age-dependent manner in WT mice and worsened in HD cells and mice, leading to reduced PSD-95 levels. These results demonstrate a direct role of HSF1 in synaptic gene regulation that has important implications in synapse maintenance in basal and pathological conditions.

African swine fever (ASF) is one of the most important and devastating viral diseases in wild boar and domestic pigs worldwide. In the absence of vaccines or treatment options, early clinical detection is key and requires sound knowledge of disease characteristics. To provide practitioners and state veterinarians with detailed information, the objective of the present study was to characterize the ASF virus (ASFV) isolate “Belgium 2018/1” in subadult and weaning domestic pigs. To this end, two animal trials were performed. Trial A included eight subadult domestic pigs and trial B five weaner pigs. In general, clinical signs and pathological lesions were in line with previous studies utilizing highly virulent ASF genotype II viruses. However, in trial A, four subadult domestic pigs survived and recovered pointing to an age dependent outcome. The long-term fate of those survivors remains under discussion and would need further investigations.

Novel mechanism of ccRCC progression is essential, including PBRM1, BAP1, and SETD2 in histone-modifying and chromatin remodeling genes. The study aimed to investigate VHL, PD-1, PD-L1, PD-L2. BAP1, PBRM1, SETD2 expression in ccRCC primary cancers and metastatic tissues associated with the cancer dissemination. A total of 62 patients with RCC were enrolled in the study. Investigation of mRNA level of VHL, PD-1, PD-L1, PD-L2. PCR in real-time performed BAP1, PBRM1, SETD2 with the previous RNA isolation. Western Blotting analysis was used for detecting the p-VHL protein content in tissues. The VHL expression and p-VHL content determined the aggressive cancer behavior and elevated in disseminated tumors. The cancer dissemination was accompanied by an increase in both mRNA and VHL content. The PD-L2 prevalence in metastatic cancers is crucial in tumor progression. ccRCC progression in VHL overexpression is associated with the decrease in BAP1 gene expression. It is revealed the heterogeneity in molecular markers in primary tumors and metastases. The low mRNA level of BAP1, PBRM1, SETD2, PD-1, PD-L1, PD-L2 in metastases compared with primary tumors were found. We show a novel mechanism for VHL tumor progression and present a new instrument and factor targeting tumor-related pathologies with p-VHL/HIF altered function.

SARS-CoV-2 infection produces a response of the innate immune system causing oxidative stress and a strong inflammatory reaction termed ‘cytokine storm’ that is one of the leading causes of death. Paraoxonase-1 (PON1) protects against oxidative stress by hydrolyzing lipoperoxides. Alterations in PON1 activity have been associated with pro-inflammatory mediators such as the chemokine (C-C motif) ligand 2 (CCL2) and the glycoprotein galectin-3. We aimed to investigate the alterations in the circulating levels of PON1, CCL2 and galectin-3 in 126 patients with COVID-19 and their interactions with clinical variables and analytical parameters. A machine learning approach was used to identify predictive markers of the disease. For comparisons, we recruited 45 COVID-19 negative patients and 50 healthy individuals. Our approach identified a synergy between oxidative stress, inflammation and fibrogenesis in positive patients that is not observed in negative patients. PON1 activity was the parameter with the greatest power to discriminate between patients who were either positive or negative for COVID-19, while their levels of CCL2 and galectin-3 were similar. We suggest that the measurement of serum PON1 activity may be a useful marker for the diagnosis of COVID-19.

Background: We aimed to describe the patterns, management, and outcome of traumatic femoral shaft fractures. Methods: An observational descriptive retrospective study was conducted for all trauma patients admitted with femoral shaft fractures between January 2012 and December 2015 at the only level 1 trauma center and tertiary hospital in the country. Data were analyzed and compared according to the time to intramedullary nailing, mechanisms of injury and age groups. Main outcomes included in-hospital complications and mortality Results: A total of 605 cases were analyzed, with mean age of 30.7±16.2 years. The majority of fractures were unilateral (96.7%) and 91% were closed fractures. Three-fourth of fractures were treated by reamed intramedullary nailing (rIMN); antegrade in 80%. The pyriform fossa nails were used in 71.6% while trochanteric entry nails were used in 28.4%. Forty-five (8.9%) of fractures were treated with external fixator, 37 (6.1%) had conservative management. Traffic-related injuries occurred more in patients aged 14-30 years whereas; injuries related to fall were significantly higher in patients aged 31-59 years. Thirty-one patients (7.8%) had rIMN < 6 h post-injury, 106 (25.5%) had rIMN < 6-12 h and 267 (66.8%) had rIMN > 12 h. The implant type, duration of surgery, DVT prophylaxis, in-hospital complications and mortality were comparable among the three treatment groups. Conclusion: In our center, the frequency of femoral fracture is 11% which mainly affects severely injured young males due to traffic-related collisions or falls. Further multicenter studies are needed to reach a consensus for the appropriate management based on the location and timing of injury

The objective of this study is to investigate whether the sequence length of HIV-1 increases over time. A longitudinal analysis of full-length coding region sequences (FLs) in an outbreak of HIV-1 infection among patients with hemophilia and local controls identified as infected with the Korean subclade B of HIV-1 (KSB). Genes amplified by overlapping RT-PCR or nested PCR were subjected to direct sequencing. In total, 141 FLs were sequentially determined over 30 years in 62 KSB-infected patients. Non-KSB sequences were retrieved from the Los Alamos National Laboratory HIV Database. Phylogenetic analysis indicated that within KSB, 2 FLs from plasma donors O and P comprised two clusters together with 8 and 12 patients with hemophilia, respectively. Signature pattern analysis for the KSB of HIV-1 revealed signature nucleotide residues at 1.05%, compared with local controls. Additionally, in-depth FLs sequence analysis over 30 years in KSB indicates that the KSB FL significantly increases over time before combined antiretroviral therapy (cART) and decreases on cART. Furthermore, the increase in FLs over time significantly occurred in the subtypes B, C and G, but, there was no increase in the subtypes D, A, and F1. Consequently, subtypes F1 and D had the shortest sequence length. Our analysis was extended to compare HIV-1 with HIV-2 and SIVs. Essentially, the longer the sequence length (SIVsm > HIV-2 > SIVcpz > HIV-1), the longer the survival period. The increase in the length of the HIV-1 sequence over time suggests that it might be an evolutionary direction toward attenuated pathogenicity.

Sentinel-1A/B radar remote sensing data were applied for the first time to determine the sixth nuclear test, its underground explosion h-bomb location and affected zone in North Korea, on September 3, 2017. Location of epicenters nuclear test were found according to line-of-sight displacement images via its maximum value. Line-of-sight displacement images were obtained by processing in the GMTSAR package in the VirtualBox virtual machine of the Linux Ubuntu 16.04 operation system. In this research, three scenes Sentinel-B data with descending orbits were considered, one after and two before the event (the nuclear test date) scene were used.

Objective: We previously provided evidence to confirm that soluble Fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and their ratio, are useful tools to direct the management of preeclampsia (PE), fetal growth restriction (FGR), and PE+FGR near delivery. In this study we examine the potential additive value of Inhibin-A, a hormone marker of the transforming growth factor family. Methods: We used a cohort of 125 pregnant women enrolled near delivery at clinics of the University Medical Center of Ljubljana, Slovenia. There were 31 cases of PE, 16 of FGR, 42 of PE+FGR, 15 iatrogenic preterm delivery (PTD), and 21 unaffected controls with delivery of a healthy baby at term. Cases delivered before 34 weeks’ gestation included 13 of PE, 12 of FGR, 22 of PE+FGR, and 6 of PTD. We recorded demographic characteristics and medical history and the levels of PlGF, sFlt-1 and Inhibin-A. The predictive accuracy of each biomarker, their ratios, and combinations was estimated from areas under the curve (AUC) of Receiver Operating Characteristics (ROC) curves. We estimated accuracy by the continuous marker model and a cut-off model. Results: Combining Inhibin-A with PlGF or with the sFlt-1 / PlGF ratio showed a 10-20% increase in AUCs and 5-15% increase in the detection rate, at 10% false positive rate, of PE, and a lower, but significant, increase for PE+FGR but not for FGR alone. The use of a cut-off model was adequate, although a bit higher accuracy was obtained from the continuous model. Highest correlation was found for PlGF with all three complications. Conclusion: Inhibin-A improves the accuracy of predicting PE and PE+FGR provided by the angiogenic markers alone, bringing the results to a diagnostic level, thus assisting in directing clinical management. Inhibin-A had no added value for the accuracy of predicting FGR alone.

Aim: To establish, through molecular modelling, safe and clinically acceptable putative antagonists of E571K-mutated exportin-1 among the bioactive compounds in various parts of Juglans mandshurica. Methods: The bioactive compounds were subjected to compendium of druglikeness and lead-likeness filter workflows prior to docking of the resultant compounds into E571K exportin-1 active site using PyRx AutoDock vina to establish their binding affinity and interaction profile. The evolutionary algorithm of Osiris property explorer DataWarrior software as well as lead-likeness filter were employed for generation of novel non-promiscuous analogues of the lead compound with better putative selectivity and clinical acceptability as E571K Exportin-1 antagonists.Results: The findings of this study present taxifolin as the putatively effective and lead-like E571K Exportin-1 inhibitor with high potential of qualifying for clinical evaluation but is associated with high promiscuity tendency in high throughput screening. The evolutionary derivation of novel analogues of the compound, however, results in the generation of putatively non-promiscuous, non-toxic, and lead-like E571K Exportin-1 antagonists with high synthetic accessibility and clinical developability for evaluation in the strategy for treatment of drug-resistant KRAS-mutant lung adenocarcinoma condition.

Our recent study detected the expression of a tissue Renin-Angiotensin System (tRAS) in human intervertebral discs (IVDs). The present study sought to investigate the impact of angiotensin II receptor type 1 (AGTR1) antagonist losartan on human nucleus pulposus (NP) cell inflammation and degeneration induced by tumor necrosis factor-α (TNF-α). Human NP cells (4 donors, Pfirrmann grade 2-3, 30-37 years old, male) were isolated and expanded. TNF-α (10 ng/mL) was used to induce inflammation and degeneration. We examined the impact of losartan supplementation and measured gene expression of tRAS, anabolic, catabolic, and inflammatory markers in NP cells after 24 h and 72 h of exposure, respectively. T0070907, a PPAR-gamma antagonist, was applied to examine the regulatory pathway of losartan. Losartan (1 mM) significantly impaired TNF-α induced increase of pro-inflammatory (nitric oxide and TNF-α), catabolic (matrix metalloproteinases), and tRAS (AGTR1a and Angiotensin Converting Enzyme) markers. Further, losartan maintained the NP cell phenotype by upregulating aggrecan and downregulating collagen type I expression. In summary, losartan showed anti-inflammatory, anti-catabolic, and positive phenotype modulating effects on human NP cells. These results indicate that tRAS signaling plays an important role in IVD degeneration, and tRAS modulation with losartan could represent a novel therapeutic approach.

The proportion of area under various crops at a given point in time, known as a cropping pattern, plays an essential role in determining the level of agricultural production. In this study, cropping patterns of three sub-counties in Murang’a County, a typical African smallholder farming area in Kenya, were mapped. Specifically, we compared the performance of eight classification scenarios for mapping cropping patterns; namely using (i) only Sentinel-2 reflectance bands (S2), (ii) S2 and S2 derived vegetation indices (VIs); (iii) S2 and S2 vegetation phenology (VP); (iv) S2 and Sentinel-1 radar backscatter data (S1); (v) S2, VIs, and S1; (vi) S2, VP, and S1; (vii) S2, VIs and VP, and (viii) S2, VIs, VP and S1. Reference data of the dominant cropping patterns and non-croplands were collected. The guided regularized random forest (GRRF) algorithm was used to select the optimum variables and to perform the respective classification for each scenario. The most accurate result of the overall accuracy of 93.16% was attained from the scenario (viii) S2, VIs, VP, and S1. The McNemar’s test of significance did not show significant differences (p≤0.05) among the tested scenarios. Our study demonstrated the strength of GRRF and the synergetic advantage of S2 and S1 derivatives to map cropping patterns in a heterogeneous landscape where high resolution imagery are inaccessible. Our cropping pattern mapping approach can be used in other sites of relatively similar agro-ecological conditions.

Due to the SARS-CoV-2 pandemic a shortage of personal protective equipment, including surgical facemasks and Filtering Facepiece Particle Respirators has occurred. SARS-CoV-2 has a 79,5-82% homology to SARS-CoV. The SARS-CoV UVC sensitivity is described in literature. We have performed UVC transmission measurements of surgical facemasks and respirators. In addition, we performed UVC disinfection experiments of S. aureus with surgical facemasks and respirators. Results show that we can achieve an 8-log reduction of S. aureus in the inner layers of FFP1 respirators and the exterior of surgical facemasks. Furthermore, we showed a 7-log reduction of S. aureus in the inner layers of FFP2 respirators. We conclude that UVC disinfection is an effective, safe and scalable method for reuse of surgical facemask and respirators.

Acute myeloid leukemia (AML) is an incurable hematological malignancy. To treat the disease successfully, new therapeutic strategies are urgently needed. One of these strategies can be the use of neurokinin-1 receptor (NK-1R) antagonists (e.g., aprepitant), because the substance P (SP)/NK-1R system is involved in cancer progression, including AML. AML patients show an up-regulation of the NK-1R mRNA expression; human AML cell lines show immunoreactivity for both SP and the NK-1R (it is overexpressed: the truncated isoform is more expressed than the full-length form) and, via this receptor, SP and NK-1R antagonists (aprepitant, in a concentration-dependent manner) respectively exert a proliferative action or an antileukemic effect (apoptotic mechanisms are triggered by promoting oxidative stress via mitochondrial Ca++ overload). Aprepitant inhibits the formation of AML cell colonies and, in combination with chemotherapeutic drugs, is more effective in inducing cytotoxic effects and AML cell growth blockade. NK-1R antagonists also exert an antinociceptive effect in myeloid leukemia-induced bone pain. The antitumor effect of aprepitant is diminished when the NF-κB pathway is overactivated and the damage induced by aprepitant in cancer cells is higher than that exerted in non-cancer cells. Thus, the SP/NK-1R system is involved in AML and aprepitant is a promising antitumor strategy against this hematological malignancy. In this review, the involvement of this system in solid and non-solid tumors (in particular in AML) is up-dated and the use of aprepitant as an anti-leukemic strategy for the treatment of AML is also mentioned (a dose of aprepitant (> 20 mg/kg/day) for a period of time according to the response to treatment is suggested).

It has been long recognized that under hypoxia conditions cancer cells reprogram their metabolism through shift from oxidative phosphorylation (OXPHOS) to glycolysis to meet elevated requirements in energy and nutrients for proliferation, migration and survival. However, data accumulated over the last years increasingly evidence that cancer cells can revert from glycolysis to OXPHOS and maintain both reprogrammed and oxidative metabolism even in the same tumor. The phenomenon denoted as cancer cell metabolic plasticity or hybrid metabolism depends on a tumor micro-environment, which is highly heterogeneous and influenced by intensity of vasculature and blood flow, oxygen concentration, nutrient and energy supply, and requires regulatory interplay between multiple oncogenes, transcription factors, growth factors, reactive oxygen species (ROS), etc. Hypoxia-inducible factor-1 (HIF-1) and AMP-activated protein kinase (AMPK) represent key modulators of switch between reprogrammed and oxidative metabolism. The present review focuses on cross-talks between HIF-1, GLUTs, and AMPK and other regulatory proteins including oncogenes such as c-Myc, p53 and KRAS, growth factor-initiated PKB/Akt, PI3K and mTOR signaling pathways and tumor suppressors such as LKB1 and TSC1 in controlling cancer cell metabolism. The multiple switches between metabolic pathways can underlie chemo-resistance to conventional anti-cancer therapy and should be taken into account in choosing molecular targets to discovery novel anti-cancer drugs.

For voltage-gated Ca2+ channel (VGCC), its α2δ subunits are traditionally considered to be auxiliary subunits that regulates VGCC trafficking to the plasma membrane. The antiepileptic, antinociceptive and anxiolytic gabapentin (GBP) has previously been shown to bind the VGCC α2δ subunits with high affinity to disrupt VGCC trafficking. Yet, the interaction between GBP and α2δ still remains poorly understood from a structural point of view. For instance, it is not clear yet what the structural implication is of α2δ-1-bound GBP against VGCC trafficking. With a set of experimental data-driven structural analysis of the VGCC α2δ-1 and its ligand GBP, this article postulates for the first time that: 1), α2δ-1 bound GBP stabilizes the α2δ-1-GBP complex structure; 2), α2δ-1 bound GBP restrains the conformational flexibility of α2δ-1; 3), α2δ-1-bound GBP establishes an electrostatic axis consisting of Q535 (Gln535)-R241 (Arg241)-GBP (gabapentin)-D452 (Asp452), which constitutes an energetically favourable contribution towards the structural stability of the α2δ-1-GBP complex and helps restrains the conformational flexibility and local structural rigidification of α2δ-1; and 4), GBP-induced local conformational inflexibility and structural rigidification of α2δ-1 is one key step in the pharmacological disruption of VGCC trafficking by GBP.

The involvement of the angiotensin II type 1 receptor in the Frank-Starling Law of the Heart, where the various activations are very limited, allows simple analysis of the kinase systems involved and thence extrapolation of the mechanism to that of angiotensin control of activation of cardiac and skeletal muscle contraction. The involvement of phosphorylation of the myosin light chain in the control of contraction is accepted but not fully understood. The involvement of troponin-I phosphorylation is also indicated but of unknown mechanism. There is no known signal for activation of myosin light chain kinase or Protein Kinase C-βII other than Ca²⁺/calmodulin but the former is constitutively active and thus has to be under control of a regulated inhibitor, the latter kinase may also be the same. Ca²⁺/calmodulin is not activated in Frank-Starling, i.e. there are no diastolic or systolic [Ca²⁺] changes. I suggest here that that the regulated inhibition is by myosin light chain phosphatase and/or β-arrestin. Angiotensin activation is by translocation of the β-arrestin from the sarcoplasm to the PM thus reducing its kinase inhibition action in the sarcoplasm, this reduced inhibition has been wrongly attributed to a mythical downstream agonist property of β-arrestin.

A Multicomponent Reaction (MCR) strategy, alternative to the known cycloaddition reaction, towards variously substituted 1-amino-1H-imidazole-2(3H)-thione derivatives has been successfully developed. The novel approach involves α-halohydrazones whose azidation process followed by tandem Staudinger/aza-Wittig reaction with CS₂ in a sequential MCR regioselectively leads to the target compounds avoiding the formation of the regioisomer iminothiazoline heterocycle. The approach can be applied to a range of differently substituted α-halohydrazones bearing also electron-withdrawing groups confirming the wide scope and the substituent tolerance of the process for the synthesis of the target compounds. Interestingly, the concurrent presence of reactive functionalities in the scaffolds so obtained, ensures postmodifications in view of N-bridgedheaded heterobicyclic structures.

Signal-to-noise ratio (SNR) is an important index to evaluate radiation performance and image quality of optical imaging systems under low illumination background. Under the nighttime lighting condition, the illumination of remote sensing objects is low and varies greatly, usually ranging from several lux to tens of thousands of lux. Nighttime light remote sensing imaging requires high sensitivity and large dynamic range of detectors. Luojia 1-01 is the first professional nighttime light remote sensing satellite in the world. In this paper, we took the nighttime light remote sensing camera carried on the satellite as research object, proposed an in-orbit SNR test method based on time series images to overcome the problem of low spatial resolution. We first analyzed the process of luminous flux transmission between objects and satellite and established a radiative transfer model. By combining the parameters of large relative aperture optical system and high sensitivity CMOS device, we established SNR model and specially analyzed the effect of exposure time and quantization bits on SNR. Finally we used the proposed in-orbit test method to calculate SNR of lighting images acquired by satellite. And the measured result is in good agreement with the model predicted data. Under the condition of 10lx illumination, the SNR of typical objects can reach 27.02dB, which is much better than the requirement of 20dB for engineering application.

A novel and simple method to improve the corrosion resistance of copper by constructing a 3D 1-dodecanethiol self-assembled monolayers (SAMs) in 3.5% NaCl solution is reported in this study. Several drops of 1% H3PO4 solution are thinly and uniformly distributed on copper surface to form a 3D nanostructure constituted by Cu3(PO4)2 nanoflowers. The anticorrosion properties of 1-dodecanethiol SAMs on copper surface and on copper surface treated with H3PO4 solution were evaluated. Results demonstrated that 1-dodecanethiol SAMs on bare copper surface exhibit good protection capacity, whereas a copper surface pretreated with H3PO4 solution can substantially enhance the corrosion resistance of 1-dodecanethiol SAMs.

Background: Even though a number of studies have verified the positive effect of physical activity (PA) on self-related health (SRH) no previous research has examined this association among pediatric patients with Type 1 diabetes mellitus (T1DM). Objective: The purpose of this study was to investigate the association between regular physical activity (PA) and self-rated health (SRH) in pediatric patients with Type 1 diabetes mellitus (T1DM) who lacked diabetes care. Methods: We conducted a retrospective study among pediatric patients with T1DM who lacked diabetes care and were enrolled in a diabetes education program between January 2011 to January 2015 at the endocrinology clinic of Seoul National University Children’s Hospital in South Korea. The eligible participants for this study were 37 pediatric patients with T1DM aged 9 to 17 years. PA was divided into regular PA and muscle strength exercise to analyze the relationship with SRH using binomial logistic regression analysis. Results: The results showed SRH of pediatric patients with T1DM who did not engage in regular PA was significantly lower than those who did (OR in regular PA = .199 [95% CI: .040, .995]; OR in regular muscle strength exercise = .097 [95% CI: .023, .825]). Conclusions: In conclusion, regular PA and muscle strength exercise in pediatric patients with T1DM who lacked diabetes care were effective in improving their SRH. A systematic plan is required to enhance regular PA for pediatric patients with T1DM.

The role of epigenetic alterations in the pathogenesis of age-related macular degeneration (AMD) has been pending so far. Our study investigated the effect of oxidative stress and inflammation on DNA methyltransferases (DNMTs) and Sirtuin 1 (SIRT1) functions, as well as on long interspersed nuclear element-1 (LINE-1) methylation, in human retinal pigment epithelial (ARPE-19) cells. Therefore, we evaluated whether treatment with resveratrol may restore changes in LINE-1 methylation by modulating DNMTs and SIRT1 functions. Cells were treated with 25 mU/ml glucose oxidase (GOx) or 10 µg/ml lipopolysaccharide (LPS) to mimic oxidative or inflammatory conditions, respectively. Oxidative stress decreased DNMT1, DNMT3a, DNMT3b and SIRT1 expression (p-values <0.05), as well as total DNMTs (-28.5%; p<0.0001) and SIRT1 (-29.0%;p<0.0001) activities. Similarly, inflammatory condition decreased DNMT1 and SIRT1 expression (p-values<0.05), as well as total DNMTs (-14.9%;p=0.007) and SIRT1 (-20.1%;p<0.002) activities. Interestingly, GOx- and LPS-treated cells exhibited lower LINE-1 methylation compared to controls (p-values<0.0001). We also demonstrated that treatment with 10 μM resveratrol for 24 hours counteracted the detrimental effect on LINE-1 methylation via increasing DNMTs and SIRT1 functions in cells upon oxidative and inflammatory conditions. However, further studies should explore the perspectives of resveratrol as a suitable strategy for the prevention and/or treatment of AMD.

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

Drug nanosuspensions offer a promising approach to improve bioavailability for poorly soluble drug candidates. Such formulations often necessitate the inclusion of an excipient to stabilize the drug nanoparticles. However, a rationale to choose the correct excipient for a given drug candidate remains unclear. To gain molecular insight into formulation design, this work first utilizes molecular dynamics simulation to computationally investigate drug-excipient interactions for a number of combinations that have been previously studied experimentally. We find that hydrophobic interactions drive excipient adsorption to drug nanoparticles, and that the fraction of polar surface area serves as a predictor for experimental measurements of nanosuspension stability. To test these ideas prospectively, we applied our model to an uncharacterized drug compound, GDC-0810. Our simulations predicted that salt forms of GDC-0810 would lead to more stable nanosuspensions than the neutral form; therefore, we tested the stability of salt GDC-0810 nanosuspensions and found that the salt form readily formed nanosuspensions even without excipient. To avoid computationally expensive simulations in the future, we extended our model by showing that simple, two-dimensional properties of the single drug molecule can be used to rationalize nanosuspension design without simulation. In all, our work demonstrates how computational tools can provide molecular insight into drug-excipient interactions, and aid in rational formulation design.

Burn-induced cardiac dysfunction is thought to involve mitochondrial dysfunction although the mechanisms responsible are unclear. In this study, we used our established model of in vivo burn injury to understand the genetic evidence of burn-induced mitochondrial metabolism confusion by describing cardiac mitochondrial metabolism-related gene expression after burn. Cardiac tissue was collected at 24 hours after burn injury. An O2K respirometer system was utilized to measure cardiac mitochondrial function. Oxidative phosphorylation complex activities were determined using enzyme activity assays. RT Profiler PCR array was used to identify differential regulation of genes involved in mitochondrial biogenesis and metabolism. Quantitative qPCR and Western Blotting were applied to validate differentially expressed genes. Burn-induced cardiac mitochondrial dysfunction was supported by the finding of decreased state 3 respiration and decreased mitochondrial electron transport chain activity in complex I, III, IV, and V following burn injury. Eighty-four mitochondrial metabolism-related gene profiles were measured. The mitochondrial gene profile showed that one third of genes related to mitochondrial energy and metabolism was differentially expressed. Of these 28 genes, 15 were more than 2-fold upregulated and 13 were more than 2-fold downregulated. All genes were validated using qPCR; 4 genes had a protein level which correlated with the observed change in gene expression. This study provides preliminary evidence that a large percentage of mitochondrial metabolism-related genes in cardiomyocytes were significantly affected by burn injury.

We propose a novel approach for time series forecasting with many predictors, referred to as the GO-sdPCA, in this paper. The approach employs a variable selection method known as the group orthogonal greedy algorithm and the high-dimensional Akaike information criterion to mitigate the impact of irrelevant predictors. Moreover, a novel technique, called peeling, is used to boost the variable selection procedure so that many factor-relevant predictors can be included in prediction. Finally, the supervised dynamic principal component analysis (sdPCA) method is adopted to account for the dynamic information in factor recovery. In simulation studies, we found that the proposed method adapts well to unknown degrees of sparsity and factor strength, which results in good performance even when the number of relevant predictors is large compared to the sample size. Applying to economic and environmental studies, the proposed method consistently performs well compared to some commonly used benchmarks in one-step-ahead out-sample forecasts.

Abstract Background: Metabolic syndrome (MetS) is a complex disorder characterized by insulin resistance (IR), central obesity, atherogenic dyslipidemia and higher glucose levels. It increases the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), imposing an economic burden on the healthcare system. However, the historical origins of MetS as well as the development and evolution of its definitions have not been conclusively documented in the literature. Aim: This study seeks to enhance the understanding of the developmental trends of MetS during the preceding two decades, placing particular emphasis on the definition, diagnosis and prevalence. Methods: An extensive search was performed from 1920 to 2023 across prominent scientific research engines, including Scopus, PubMed, MDPI, and others. Results: Despite advancements, many aspects of MetS remain inadequately understood. As the understanding of the nature and pathophysiology of MetS progresses, the development and refinement of its diagnostic criteria, and assessment and treatment guidelines will continue. Additionally, there exists significant variation in the global prevalence of metabolic syndrome, ranging from 14 to 39%. This prevalence is projected to increase due to the adoption of less healthy dietary patterns and sedentary lifestyles. The observed disparities in metabolic syndrome prevalence can be attributed to multiple factors, including demographic characteristics. Furthermore, the lack of a standardized definition across studies also contributes to the variation in reported prevalence rates. Conclusion: Further studies focusing on the standardization of the MetS definition across different research are crucial. The establishment of consistent criteria would enhance the reliability and validity of research findings, enabling more meaningful comparisons and interpretations.

Increased CO2 emissions and air pollution impact the environment and human health. In this manner, new functionalized polyaminal-based polymers are synthesized via a one-pot polycondensation reaction of melamine with aldehyde monomers 2-bromo-1-naphthaldehyde and 2-hydroxy-1-naphthaldehyde to yield bromine- hydroxyl- functionalized polymer networks PAN-BrNA and PAN-HNA, respectively. The polyaminals porosity parameters were investigated and applied as an adsorbent for CO2 capture. FTIR, solid-state 13C NMR, and X-ray diffraction verified the PANs structure development. A scanning electron microscope and N2 adsorption-desorption methods were utilized to identify the porous properties of the polymers at 77 K. The Brunauer-Emmett-Teller (BET) surface area of PAN-BrNA and PAN-HNA is (16.6990 m2/g) and (716.7568 m2/g), respectively. At 273 K, PAN-BrNA and PAN-HNA can take CO2 gas up to (4.42786 cm3/g) and (47.55 cm3/g), respectively. The findings show that inserting functional groups has a significant impact on surface area and porosity parameters, as well as CO2 uptake.

Milkfish (Chanos chanos) locally called Bangus in the Philippines, is a popular food fish in terms of production and consumption in the Philippines, Indonesia and Taiwan. This study characterized a typical grow-out milkfish farm in the Davao region in terms of socioeconomic profile, farming practices, and simple costs and returns. Three sites were chosen to conduct this study, mainly in Mati, Pantukan and Panabo in Davao region where N=43 farm workers provided information on their daily farming practices. Farms are commonly stocked with 16,000 fingerlings, harvesting occurs after every 6 months with six feeding times in a day. Moreover, workers were paid an average of Php 10,000 per month while the company had a gross income of Php 930,000 per cropping cycle. The feed cost shares 76% of the overall operational cost with a 27% return on investment for the first year of operation. Climate change impacts (e.g. higher sea surface temperature, unpredictable weather and flooding) and deteriorating water quality conditions were seen as bigger threats. Other results showed a positive relationship between stocking density and volume harvested (df=1, MS=0.0907, F=40.13, P=0.000) and income (df=1, MS=0.048, F=21.22, P=0.000). The study also showed the need for cheaper feed substitute and better benefits to farm workers.

This article presents a method that uses a semi-automatic algorithm for the detection and analysis of microcracks in steel test specimens using binarized image analysis. It obtains the length along the crack path in contrast to previous methods that have obtained linear length, thereby achieving a closer approximation to its actual value. Additionally, this method automatically calculates the COD and COA parameters with measurement deviations in micrometres, thus providing greater precision than previous methods proposed to date.

Rhabdomyosarcoma is a cancer arising from arrested myogenic differentiation, seen mainly in children or adolescents. Metastatic rhabdomyosarcoma is often fatal even with aggressive cytotoxic chemotherapies, surgery, and irradiation. SALIQ is an acronym for a multidrug augmentation regimen designed as an adjunct to current rhabdomyosarcoma chemotherapies. SALIQ uses five common non-oncology drugs, repurposed from general medicine use, to promote malignant clone maturation and inhibit rhabdomyosarcoma growth. The five drugs are: the cholesterol lowering drug simvastatin, the acne medicine tretinoin (ATRA), the psychiatric drug lithium carbonate, the antifungal drug itraconazole, and the food supplement quercetin. All five drugs are in common use for non-cancer conditions, are cheap, have an eminently safe side effect profile, and all five have preclinical evidence and good rationale for inhibiting rhabdomyosarcoma growth.

Sustainable biomass production has significant potential for mitigating greenhouse gas emissions and is a promising alternative for the production of eco-friendly biofuels, biochemicals, and carbonaceous materials for biological, energetic, and environmental applications. Biomass from agroforestry and agricultural wastes is the richest natural carbon source and a sustainable option for woody biomass from a circular economic perspective. Portugal has several residues and by-products of agriculture, food processing, and forestry origin, and has a high availability of residual biomass. Portugal intends to reduce its dependence on energy imports and the use of fossil fuels, thereby increasing its economic performance while using biomass waste to produce high-value-added products. In this context, this review aims to explore the potential of agri-food wastes obtained from Portuguese industries via thermochemical conversion technologies as a promising sustainable alternative to woody biomass for the development of eco-friendly biofuels, biochemicals, and high-value carbonaceous materials and their applications. This strategy based on the circular bioeconomy concept can contribute to reducing the dependence on fossil fuels and minimising greenhouse gas emissions while meeting the demands of the growing population and providing a sustainable waste management solution.

: Seaweeds are among the most important biomass feedstocks for the production of third generation biofuels. They are also efficient in carbon sequestration during growth, and produce a variety of high value chemicals. Given these characteristics together with the relatively high carbohydrate content, seaweeds have been discussed as an ideal means for CO2 capture and biofuel production. Though third generation biofuels have emerged as some of the best alternatives to fossil fuels, there is currently no large-scale production or mainstream use of such liquid fuels due to the many technical challenges and high production costs. The present study describes the concept of coastal marine biorefineries as the most cost-effective and sustainable approach for biofuel production from sea-weeds as well as atmospheric carbon capture and storage (CCS). The suggested refinery system makes use of marine resources, namely seawater, seaweed, and marine microorganisms. Firstly, extensive screening of the current literature was performed to determine which technologies would enable the emergence of such a novel biorefinery system and its merits over conventional refineries. Secondly, the study investigates various scenarios assessing the potential of seaweeds as a means of carbon sequestration. We demonstrate that the removal of 100 Gigatons of excess CO2 using seaweed farms can be achieved in around 4 months to less than 12 years depending on the area under cultivation and the seaweed species. The total bioethanol that could be generated from the harvested biomass is around 8 trillion litres. In addition, high-value chemicals (HVC) that could potentially be recovered from the process represent a considerable op-portunity with multi-billion-dollar commercial value. Overall, coastal marine biorefineries have strong potential for a sustainable green economy and rep-resent a rapid approach for climate change mitigation.

A two-layer Fe-Cr-Al-Zr surface alloy was synthesized on a zirconium substrate by magnetron sputtering and subsequent low-energy high-current electron-beam (LEHCEB) processing. Thicknesses of the top Fe69Cr20Al11 (at.%) relatively large-grained (~1 µm) and transition Fe-Zr Cr-Al amorphous layers were about 0.7 and 0.6 µm, respectively. In turn, the amorphous layer consisted of two Fe64–54Zr8–22Cr21–17Al8–7 and Fe40–16Zr42–78Cr12–4Al6–2 (at.%) sublayers, differing in both zirconium and iron concentrations in wide ranges, which were separated by another nanocrystalline interlayer. The Fe-Cr-Al-Zr surface alloy serve as a diffusion barrier, preventing interaction of the zirconium substrate with oxygen from an environment. It was thermally stable up to ≈1173 K.

Alunogen, Al2(SO4)3·17H2O, occurs as an efflorescent in acid mine drainage, low-temperature fumarolic or pseudofumarolic (at coal fires) terrestrial environments. It is considered as one of the main Al-sulfates of Martian soils demanding comprehensive crystal chemical data of natural terrestrial samples. However, structural studies of natural alunogen were carried out in 1970s without localization of H atoms and have not previously been performed for samples from geothermal fields, despite the fact that these environments are considered as proxies of the Martian conditions. The studied alunogen sample comes from Verkhne-Koshelevsky geothermal field (Koshelev volcano, Kamchatka, Russia). Its chemical formula is somewhat dehydrated, Al2(SO4)3×15.8 H2O. The crystal structure was solved and refined to R1 = 0.068 based on 5112 unique observed reflections with I > 2σ(I). Alunogen crystalizes in P-1 space group, a = 7.4194(3), b = 26.9763(9), c = 6.0549(2) Å, α = 90.043(3), β = 97.703(3), γ = 91.673(3) °, V = 1200.41(7) Å3, Z = 2. The crystal structure consists of isolated SO4 tetrahedra, Al(H2O)6 octahedra and H2O molecules connected by hydrogen bonds. The structure refinement includes Al, S and O positions that are similar to previous structure determinations and thirty-four H positions localized for the natural sample first. The study also shows the absence of isomorphic substitutions in the composition of alunogen despite the iron-enriched environment of mineral crystallization. The variability of the alunogen crystal structure is reflected in the number of “zeolite” H2O molecules and their splitting. The structure complexity of alunogen and its modifications ranges from 333-346 bits/cell for models with non-localized H atoms to 783-828 bits/cell for models with localized H atoms. The higher values correspond to higher hydration state of alunogen.

The crystal structure of quintinite, Mg4Al2(OH)12(CO3)·3H2O, from Jacupiranga alkaline complex (Cajati, São Paulo, Brazil) has been refined for two samples (91002 and C7029) using single-crystal X-ray diffraction data. The mineral crystallizes in the P-3c1 space group, a = 5.246/5.298, c = 15.110/15.199 Å for the samples 91002/C7029. The crystal structure consists of octahedral sheets with Mg and Al ordering according to the 3 × 3 superstructure. The Mg and Al atoms are coordinated by six hydroxylated oxygen atoms each with the average &lt;Mg–O&gt; and &lt;Al–O&gt; bond distances being in the ranges 2.022–2.053 Å and 1.974–1.978 Å, respectively. The interlayer structures are identical (in contradiction to the previous assumptions) and compose from disordered (CO3)2- groups and (H2O)0 molecules. The samples from Jacupiranga can be identified as quintinite-2T that is the second find of the polytype after the Kovdor alkaline complex (Kola peninsula, Russia). The powder X-ray diffraction pattern of quintinite-2T contains weak superstructure reflection at 4.57 Å (010) indicative of Mg and Al ordering. An important crystal-chemical criterion of quintinite is the interlayer distance (d00n-value) of ~ 7.56 Å, which is steady for natural specimens from various findings worldwide.

The worldwide prevalence of type 2 diabetes (T2D) and prediabetes is rapidly increasing, particularly in children, adolescents, and young adults. Oxidative stress (OxS) has emerged as a likely initiating factor in T2D. The role of natural antioxidant products in combating T2D is best evaluated in the context of the complex physiological processes that modulate T2D-OxS such as glycemic control and exercise. The role of natural antioxidant compounds such as vitamin E in T2D must likewise be considered beyond their roles as inhibitors of OxS. In addition to antioxidant properties, vitamin E vitamers (tocopherols and tocotrienols) also exhibit distinct abilities to regulate cellular signal transduction pathways important to T2D progression. Most research on the role of vitamin E in T2D or prediabetes has been limited to tocopherols (Ts) but emerging trials with tocotrienols (T3s) show promise. Minimizing factors that induce chronic damaging OxS and maximizing natural antioxidant protective factors may provide a means of preventing or slowing T2D progression. This “optimal redox” (OptRedox) approach also provides a framework in which to discuss the potential benefits of natural antioxidant factors such as antioxidant products. Since early, effective intervention is critical, the OptRedox strategy would be optimally effective if implemented in the pediatric population.

Metchnikovellids (Microsporidia: Metchnikovellida) are poorly studied hyperparasitic micro-sporidia that live in gregarines inhabiting the intestines of marine invertebrates, mostly poly-chaetes. Our recent studies showed that the diversity of the metchnikovellids might be signifi-cantly higher than previously thought, even within a single host. Four species of metchnikovellids were found in the gregarines inhabiting the gut of the polychaete Pygospio elegans from littoral populations of the White and Barents Seas: the eugregarine Polyrhabdina pygospionis is the host for Metchnikovella incurvata and M. spiralis, while the archigregarine Selenidium pygospionis is the host for M. dogieli and M. dobrovolskiji. The most common species in the White Sea is M. in-curvata, while M. dobrovolskiji prevails in the Barents Sea. The gregarines within a single worm could be infected with different metchnikovellid species. However, co-infection of one and the same gregarine with several species of metchnikovellids has never been observed. The difference in prevalence and intensity of metchnikovellid invasion apparently depends on the features of the life cycle and on the development strategies of individual species.

Land degradation and climate change are among the main threats to the sustainability of ecosystems worldwide. Therefore, the restoration of degraded landscapes is essential to maintain the functionality of ecosystems, especially those with greater social, economic and environmental vulnerability. Nevertheless, policy-makers are frequently challenged by deciding on where to prioritize restoration actions, which usually includes to deal with multiple and complex needs under an always short budget. If these decisions are not taken based on proper data and processes, restoration implementation can easily fail. To help decision-makers taking informed decisions on where to implement restoration activities, we have developed a semiautomatic geospatial platform to prioritize areas for restoration activities based on ecological, social and economic variables. This platform takes advantage of the potential to integrate R coding, Google Earth Engine cloud computing and GIS visualization services to generate an interactive geospatial decision-maker tool for restoration. Here, we present a prototype version called "RePlant alpha" which was tested with data from the Central Zone of Chile. This exercise proved that integrating R and GEE was feasible, and that the analysis, with at least six indicators and for a specific region was also feasible to implement even from a personal computer. Therefore, the use of a virtual machine in the cloud with a large number of indicators over large areas is both possible and practical.