The Stellarator Power Plant Studies Prospective R&D Work Package in the Eurofusion Programme was settled to bring the stellarator engineering to maturity, so that stellarators and particularly the HELIAS (HELical-axis Advanced Stellarator) configuration could be a possible alternative to tokamaks. However, its complex geometry makes designing a Breeding Blanket (BB) that fully satisfies the requirements for such a HELIAS configuration, which is a difficult task. Taking advantage of the acquired experience in BB design for DEMO tokamak, CIEMAT is leading the development of a Dual Coolant Lithium Lead (DCLL) BB for a HELIAS configuration. To answer the specific HELIAS challenges, new and advanced solutions have been proposed, such as the use of fully detached First Wall (FW) based on liquid metal Capillary Porous Systems (CPS). The proposed solutions have been studied in a simplified 1D model that can help to estimate the relative variations in Tritium Breeding Ratio (TBR) and displacement per atom (dpa) to verify their effectiveness in simplifying the BB integration and improving the machine availability while keeping the main BB nuclear functions (i.e., tritium breeding, heat extraction and shielding). This preliminary study demonstrates that the use of FW CPS would drastically reduce the radiation damage received by the blanket by $29\%$ in some of the selected configurations along with a small decrease of $4.9\%$ in TBR. This could even be improved to just a $3.8\%$ TBR reduction by using a graphite reflector. Such an impact on the TBR is considered affordable, and the results presented, although preliminary in essence, have shown the existence of margins for further development of the FW CPS concept for HELIAS, as they have been not found, at least to date, to be significant showstoppers for the use of this technological solution. Full article

In this work, we present a new type of fractional derivatives (FD) involving exponential cotangent function in their kernels called Riemann–Liouville $D^{\sigma ,\gamma }$ and Caputo cotangent fractional derivatives ${}^C{D}^{\sigma ,\gamma }$, respectively, and their corresponding integral $I^{\sigma ,\gamma }$. The advantage of the new fractional derivatives is that they achieve a semi-group property, and we have special cases; if $\gamma =1$ we obtain the Riemann–Liouville FD (RL-FD), Caputo FD (C-FD), and Riemann–Liouville fractional integral (RL-FI). We give some theorems and lemmas, and we give solutions to linear cotangent fractional differential equations using the Laplace transform of the $D^{\sigma ,\gamma }$, ${}^C{D}^{\sigma ,\gamma }$ and $I^{\sigma ,\gamma }$. Finally, we give the application of this new type on the SIR model. This new type of fractional calculus can help other researchers who still work on the actual subject. Full article

The circadian and stress-realizing systems are interconnected, and the balance of their interaction determines the state of human health. The objective of this study was to investigate the modulating effect of activating the circadian system on heart rate variability in female medical students with high anxiety while performing a cognitive task. After 20 min of adequate stimulation of circadian photoreceptors with a monochromatic blue light, the cognitive task performance resulted in a decrease in sympathetic impact. During the session of monochromatic blue light exposure, a trend of increasing heart rate variability was observed in a state of relative rest (especially in the first 5 min). A comparative analysis of the parameters of the letter cancellation test before and after light exposure revealed a statistically significant increase in the indexes reflecting mental productivity, work accuracy, and concentration of attention. The results suggest an essential physiological role of the human circadian system in modulating the autonomic and psycho-emotional conditions, as well as cognitive functions of individuals with high anxiety. Our findings indicate the possibility of quickly correcting the balance in human systemic regulatory mechanisms using the activation of retinal circadian photoreceptors by blue light. Full article

The steady-state redox status is physiologically important and therefore homeostatically maintained. Changes in the status result in signaling (eustress) or oxidative damage (distress). Oxidative stress (OS) is a hard-to-quantitate term that can be estimated only based on different biomarkers. Clinical application of OS, particularly for selective antioxidant treatment of people under oxidative stress, requires quantitative evaluation and is limited by the lack of universal biomarkers to describe it. Furthermore, different antioxidants have different effects on the redox state. Hence, as long as we do not have the possibility to determine and quantify OS, therapeutic interventions by the “identify-and-treat” approach cannot be assessed and are, therefore, not likely to be the basis for selective preventive measures against oxidative damage. Full article

Increasing development of infrastructure in Indonesia has driven the need for effective ground improvement methods to accelerate the consolidation of soft soil, which is estimated to occupy around 10% of the country’s land area. A prefabricated vertical drain combined with vacuum preloading is among the most effective methods for this purpose. However, the prefabricated vertical drain creates a smear zone in the surrounding soil area during installation. This study examines the effectiveness of a newly developed mandrel system in reducing the smear zone during prefabricated vertical drain installation. Large-scale consolidation tests at a macro level and microstructure analysis using scanning electron microscopy at a micro level were employed to investigate the effect of soil water content and shear strength. The results show that the water content and shear strength of the soft soil gradually increased in the inner smear zone and transition zone, while both decreased in the radial distance. Furthermore, the soil structure underwent a transformation in which the particle area and pore area became a closed flake structure, and apparent agglomeration occurred. The test results indicate that the newly developed mandrel system can effectively reduce the smear zone. The macro to micro test results demonstrated that the mandrel system is successful in reducing the smear zone effect. Full article

In hospital construction, additional challenges must be considered, such as an increased number of stakeholders and building trades, such as medical and laboratory technology. Due to the increasing requirements and challenges, associated construction processes are becoming more intricate. Especially for complex building types, the effects of this development are clearly noticeable and cause considerable disruptions to the construction process. A main difficulty constitutes the missing definition of the interfaces of building trades and participants. In the present study, interfaces in hospital construction were identified and analyzed by guided interviews with experts from the health sector. The qualitative content analysis, according to Mayring, was used for the evaluation to derive appropriate solution approaches. This paper presents the interfaces using the example of hospital construction in Germany and general approaches of optimization. Hereby, the digital method Building Information Modeling (BIM) plays a decisive role in the optimization of interfaces, especially in complex buildings. Furthermore, a task and building trade control matrix is required to better coordinate the interfaces. The identified approach intends to alleviate potential disputes and misunderstandings among stakeholders, as well as to improve time and financial predictability, which are particularly valuable during inflationary periods. Full article

Considering the technological enhancements nowadays, antennas tend to be smaller in order to be easily integrated in devices. The most used antennas today in small high-tech devices close to the human body are planar antennas. In this paper, a Yagi Uda planar antenna operating at a frequency of 2.4 GHz is HF analyzed and optimized by increasing its bandwidth and gain while maintaining its initial dimensions. The methods used to optimize the antenna’s operation are the use of different dielectrics, different numbers of directors, and different dimensions for directors, placing new conductor elements, all while keeping the same dimensions for its implementation on the planar device. The optimized structure of the planar Yagi Uda antenna has a 10% increase in bandwidth and a 30% increase in gain, reaching a peak value of 4.84 dBi. In our daily activities, we use devices with such antennas very often, so an analysis of the antenna’s influence on the human body is performed: the SAR, electric and magnetic field and radiation power density are determined, represented and reported to the standards in force. For the frequency considered, the SAR should be below 4 W/kg for the head/torso when the exposure is more than six minutes, which is a value exceeded by the antenna in its near vicinity. The calculated maximum electric field limit is 0.349 V/m and the maximum magnetic field value is 28.441 V/m for an exposure between 6 and 30 min values, which is also exceeded in the immediate vicinity of the antenna. The results allow us to suggest that such an antenna should be placed further from the human body, or some protection should be placed between the body and the antenna. From the radiation power density point of view for the modeled antenna, it can be said that a distance from the antenna greater than 0.5 m is considered to be safe. Full article

Guanine quadruplexes (G4s) are non-canonical nucleic acid structures formed by guanine (G)-rich tracts that assemble into a core of stacked planar tetrads. G4s are found in the human genome and in the genomes of human pathogens, where they are involved in the regulation of gene expression and genome replication. G4s have been proposed as novel pharmacological targets in humans and their exploitation for antiviral therapy is an emerging research topic. Here, we report on the presence, conservation and localization of putative G4-forming sequences (PQSs) in human arboviruses. The prediction of PQSs was performed on more than twelve thousand viral genomes, belonging to forty different arboviruses that infect humans, and revealed that the abundance of PQSs in arboviruses is not related to the genomic GC content, but depends on the type of nucleic acid that constitutes the viral genome. Positive-strand ssRNA arboviruses, especially Flaviviruses, are significantly enriched in highly conserved PQSs, located in coding sequences (CDSs) or untranslated regions (UTRs). In contrast, negative-strand ssRNA and dsRNA arboviruses contain few conserved PQSs. Our analyses also revealed the presence of bulged PQSs, accounting for 17–26% of the total predicted PQSs. The data presented highlight the presence of highly conserved PQS in human arboviruses and present non-canonical nucleic acid-structures as promising therapeutic targets in arbovirus infections. Full article

As an Internet of Things (IoT) technological key enabler, Wireless Sensor Networks (WSNs) are prone to different kinds of cyberattacks. WSNs have unique characteristics, and have several limitations which complicate the design of effective attack prevention and detection techniques. This paper aims to provide a comprehensive understanding of the fundamental principles underlying cybersecurity in WSNs. In addition to current and envisioned solutions that have been studied in detail, this review primarily focuses on state-of-the-art Machine Learning (ML) and Blockchain (BC) security techniques by studying and analyzing 171 up-to-date publications highlighting security aspect in WSNs. Then, the paper discusses integrating BC and ML towards developing a lightweight security framework that consists of two lines of defence, i.e, cyberattack detection and cyberattack prevention in WSNs, emphasizing the relevant design insights and challenges. The paper concludes by presenting a proposed integrated BC and ML solution highlighting potential BC and ML algorithms underpinning a less computationally demanding solution. Full article

Immunotherapy has revolutionised anti-cancer treatment in solid organ malignancies. Specifically, the discovery of CTLA-4 followed by PD-1 in the early 2000s led to the practice-changing clinical development of immune checkpoint inhibitors (ICI). Patients with lung cancer, including both small cell (SCLC) and non-small cell lung cancer (NSCLC), benefit from the most commonly used form of immunotherapy in immune checkpoint inhibitors (ICI), resulting in increased survival and quality of life. In NSCLC, the benefit of ICIs has now extended from advanced NSCLC to earlier stages of disease, resulting in durable benefits and the even the emergence of the word ‘cure’ in long term responders. However, not all patients respond to immunotherapy, and few patients achieve long-term survival. Patients may also develop immune-related toxicity, a small percentage of which is associated with significant mortality and morbidity. This review article highlights the various types of immunotherapeutic strategies, their modes of action, and the practice-changing clinical trials that have led to the widespread use of immunotherapy, with a focus on ICIs in NSCLC and the current challenges associated with advancing the field of immunotherapy. Full article

The friction stir welding (FSW) process was recently developed to overcome the difficulty of welding non-ferrous alloys and steels. In this study, dissimilar butt joints between 6061-T6 aluminum alloy and AISI 316 stainless steel were welded by FSW using different processing parameters. The grain structure and precipitates at the different welded zones of the various joints were intensively characterized by the electron backscattering diffraction technique (EBSD). Subsequently, the FSWed joints were tensile tested to examine the mechanical strength compared with that of the base metals. The micro-indentation hardness measurements were conducted to reveal the mechanical responses of the different zones in the joint. The EBSD results of the microstructural evolution showed that a significant continuous dynamic recrystallization (CDRX) occurred in the stir zone (SZ) of the Al side, which was mainly composed of the weak metal, Al, and fragmentations of the steel. However, the steel underwent severe deformation and discontinuous dynamic recrystallization (DDRX). The FSW rotation speed increased the ultimate tensile strength (UTS) from 126 MPa at a rotation speed of 300 RPM to 162 MPa at a rotation speed of 500 RPM. The tensile failure occurred at the SZ on the Al side for all specimens. The impact of the microstructure change in the FSW zones was significantly pronounced in the micro-indentation hardness measurements. This was presumably attributed to the promotion of various strengthening mechanisms, such as grain refinement due to DRX (CDRX or DDRX), the appearance of intermetallic compounds, and strain hardening. The aluminum side underwent recrystallization as a result of the heat input in the SZ, but the stainless steel side did not experience recrystallization due to inadequate heat input, resulting in grain deformation instead. Full article

This paper provides an overview of an early attempt at developing a simulation model on a solid-state transformer (SST) based on input-serial and output-parallel (ISOP) topology. The proposed SST is designed as a base for a smart grid (SG). The paper provides a theoretical review of the power converters under consideration, as well as their control techniques. Further, the paper presents a simulation model of the proposed concept with a PLECS circuit simulator. The proposed simulation model examines bidirectional energy flow control between the medium-voltage AC grid and DC smart grid, while evaluating power flow efficiency and qualitative indicators of the AC grid. After the completion of design verification and electrical properties analysis by the PLECS simulation models, the synthesis offers recommendations on the optimal layout of the proposed SST topology for smart grid application. Full article

P4, a specific combination of dairy proteins (whey and casein) and plant-based protein isolates (pea and soy), has been shown to provide a more balanced amino acid (AA) profile than its single constituent proteins; however, less is known about how this translates to muscle protein synthesis (MPS). The aim of this study was to investigate the effect of P4 compared to whey or casein against fasted control on MPS. C57BL/6J mice, aged 25 months, were fasted overnight, followed by oral gavage of either whey, P4, casein, or water as a fasted control. Thirty minutes after ingestion, puromycin (0.04 µmol∙g^-1 bodyweight) was subcutaneously injected; 30-min thereafter, mice were sacrificed. MPS was measured by the SUnSET method, and signalling proteins were determined in the left-tibialis anterior (TA) muscle by the WES technique. AA composition was determined in plasma and right-TA muscle. Dried blood spots (DBS) were analysed for postprandial AA dynamics at 10, 20, 45, 60 min. MPS was 1.6-fold increased with whey (p = 0.006) and 1.5-fold with P4 compared to fasted (p = 0.008), while no change was seen with casein. This was confirmed by a significant increase of phosphorylated/total ratio of 4E-BP1 for both whey (p = 0.012) and P4 (p = 0.001). No changes were observed in p70S6K and mTOR phosphorylation/total ratio with whey or P4. Intramuscular leucine levels were lower for P4 (0.71 µmol∙g dry weight⁻¹) compared to whey (0.97 µmol∙g dry weight⁻¹) (p = 0.0007). Ten minutes postprandial, DBS showed significantly increased blood AA levels of BCAAs, histidine, lysine, threonine, arginine, and tyrosine for P4 versus fasted. In conclusion, a hybrid mix of dairy and plant-based proteins (P4) resulted in a MPS response that was similar to whey protein in aged mice after fasting. This suggests that other anabolic triggers beyond leucine or the well-balanced amino acid profile and bioavailability of the blend benefit stimulation of MPS. Full article

Knowledge about anatomical shape variations in the pelvis is mandatory for selection, fitting, positioning, and fixation in pelvic surgery. The current knowledge on pelvic shape variation mostly relies on point-to-point measurements on 2D X-ray images and computed tomography (CT) slices. Three-dimensional region-specific assessments of pelvic morphology are scarce. Our aim was to develop a statistical shape model of the hemipelvis to assess anatomical shape variations in the hemipelvis. CT scans of 200 patients (100 male and 100 female) were used to obtain segmentations. An iterative closest point algorithm was performed to register these 3D segmentations, so a principal component analysis (PCA) could be performed, and a statistical shape model (SSM) of the hemipelvis was developed. The first 15 principal components (PCs) described 90% of the total shape variation, and the reconstruction ability of this SSM resulted in a root mean square error of 1.58 (95% CI: 1.53–1.63) mm. In summary, an SSM of the hemipelvis was developed, which describes the shape variations in a Caucasian population and is able to reconstruct an aberrant hemipelvis. Principal component analyses demonstrated that, in a general population, anatomical shape variations were mostly related to differences in the size of the pelvis (e.g., PC1 describes 68% of the total shape variation, which is attributed to size). Differences between the male and female pelvis were most pronounced in the iliac wing and pubic rami regions. These regions are often subject to injuries. Future clinical applications of our newly developed SSM may be relevant for SSM-based semi-automatic virtual reconstruction of a fractured hemipelvis as part of preoperative planning. Lastly, for companies, using our SSM might be interesting in order to assess which sizes of pelvic implants should be produced to provide proper-fitting implants for most of the population. Full article

Existing deep learning-based methods for detecting fake news are uninterpretable, and they do not use external knowledge related to the news. As a result, the authors of the paper propose a graph matching-based approach combined with external knowledge to detect fake news. The approach focuses on extracting commonsense knowledge from news texts through knowledge extraction, extracting background knowledge related to news content from a commonsense knowledge graph through entity extraction and entity disambiguation, using external knowledge as evidence for news identification, and interpreting the final identification results through such evidence. To achieve the identification of fake news containing commonsense errors, the algorithm uses random walks graph matching and compares the commonsense knowledge embedded in the news content with the relevant external knowledge in the commonsense knowledge graph. The news is then discriminated as true or false based on the results of the comparative analysis. From the experimental results, the method can achieve 91.07%, 85.00%, and 89.47% accuracy, precision, and recall rates, respectively, in the task of identifying fake news containing commonsense errors. Full article

In this paper, we investigate the structural and biological features of G-quadruplex (G4) aptamers as promising antiproliferative compounds affecting the STAT3 signalling pathway. Targeting the STAT3 protein through high-affinity ligands to reduce its levels or activity in cancer has noteworthy therapeutic potential. T40214 (STAT) [(G₃C)₄] is a G4 aptamer that can influence STAT3 biological outcomes in an efficient manner in several cancer cells. To explore the effects of an extra cytidine in second position and/or of single site-specific replacements of loop residues in generating aptamers that can affect the STAT3 biochemical pathway, a series of STAT and STATB [GCG₂(CG₃)₃C] analogues containing a thymidine residue instead of cytidines was prepared. NMR, CD, UV, and PAGE data suggested that all derivatives adopt dimeric G4 structures like that of unmodified T40214 endowed with higher thermal stability, keeping the resistance in biological environments substantially unchanged, as shown by the nuclease stability assay. The antiproliferative activity of these ODNs was tested on both human prostate (DU145) and breast (MDA-MB-231) cancer cells. All derivatives showed similar antiproliferative activities on both cell lines, revealing a marked inhibition of proliferation, particularly at 72 h at 30 µM. Transcriptomic analysis aimed to evaluate STAT's and STATB’s influence on the expression of many genes in MDA-MB-231 cells, suggested their potential involvement in STAT3 pathway modulation, and thus their interference in different biological processes. These data provide new tools to affect an interesting biochemical pathway and to develop novel anticancer and anti-inflammatory drugs. Full article

A substantial body of phenomenological and theoretical work over the last few years strengthens the possibility that the vacuum energy density (VED) of the universe is dynamical, and in particular that it adopts the ‘running vacuum model’ (RVM) form, in which the VED evolves mildly as $\delta {\rho }_{\mathrm{vac}}\left(H\right)\sim {\nu }_{\mathrm{eff}}{m}_{\mathrm{Pl}}^2\mathcal{O}\left(H^2\right)$, where H is the Hubble rate and ${\nu }_{\mathrm{eff}}$ is a (small) free parameter. This dynamical scenario is grounded on recent studies of quantum field theory (QFT) in curved spacetime and also on string theory. It turns out that what we call the ‘cosmological constant’, $\mathsf{\Lambda }$, is no longer a rigid parameter but the nearly sustained value of $8\pi G\left(H\right){\rho }_{\mathrm{vac}}\left(H\right)$ around any given epoch $H\left(t\right)$, where $G\left(H\right)$ is the gravitational coupling, which can also be very mildly running (logarithmically). Of particular interest is the possibility suggested in past works that such a running may help to cure the cosmological tensions afflicting the $\mathsf{\Lambda }$CDM. In the current study, we reanalyze the RVM in full and we find it becomes further buttressed. Using modern cosmological data, namely a compilation of the latest SNIa+BAO+$H\left(z\right)$+LSS+CMB observations, we probe to what extent the RVM provides a quality fit better than the concordance $\mathsf{\Lambda }$CDM model, with particular emphasis on its impact on the ${\sigma }_8$ and $H_0$ tensions. We utilize the Einstein–Boltzmann system solver CLASS and the Monte Carlo sampler MontePython for the statistical analysis, as well as the statistical DIC criterion to compare the running vacuum against the rigid vacuum (${\nu }_{\mathrm{eff}}=0$). On fundamental grounds, ${\nu }_{\mathrm{eff}}$ receives contributions from all the quantized matter fields in FLRW spacetime. We show that with a tiny amount of vacuum dynamics (${\nu }_{\mathrm{eff}}\ll 1$) the global fit can improve significantly with respect to the $\mathsf{\Lambda }$CDM and the mentioned tensions may subside to inconspicuous levels. Full article

Conversely to most tumour types, magnetic resonance imaging (MRI) was rarely used for eye tumours. As recent technical advances have increased ocular MRI’s diagnostic value, various clinical applications have been proposed. This systematic review provides an overview of the current status of MRI in the clinical care of uveal melanoma (UM) patients, the most common eye tumour in adults. In total, 158 articles were included. Two- and three-dimensional anatomical scans and functional scans, which assess the tumour micro-biology, can be obtained in routine clinical setting. The radiological characteristics of the most common intra-ocular masses have been described extensively, enabling MRI to contribute to diagnoses. Additionally, MRI’s ability to non-invasively probe the tissue’s biological properties enables early detection of therapy response and potentially differentiates between high- and low-risk UM. MRI-based tumour dimensions are generally in agreement with conventional ultrasound (median absolute difference 0.5 mm), but MRI is considered more accurate in a subgroup of anteriorly located tumours. Although multiple studies propose that MRI’s 3D tumour visualisation can improve therapy planning, an evaluation of its clinical benefit is lacking. In conclusion, MRI is a complementary imaging modality for UM of which the clinical benefit has been shown by multiple studies. Full article

This article deals with the determination of the impact of selected parameters on energy consumption for heating and cooling purposes and CO₂ emissions. Mathematical modelling combined with planning a computational experiment was adopted as the research method. The database for creating the models was developed using building energy simulations performed with DesignBuilder software. A single-family house with an area of 101 m² was the subject of this study. Four deterministic mathematical models for the estimation of annual energy demand for heating, cooling, total final energy demand, and CO₂ emissions were developed. Four parameters affecting the energy balance of the house: the area of the glazing system (three levels), U-value of windows (two-, three- and four-pane), U-value of external walls (0.1, 0.15, 0.2 W/m²K) and location (Warsaw, Berlin, Paris) were considered. The article discusses in detail the influence of individual factors on the energy demand and their common interactions. It was found that the level of thermal insulation of the glazing system plays the most important role in saving energy. This factor was the only one to show a stable and significant reduction in house energy demand, and thus a reduction in CO₂ emissions for all four objective functions. Full article

Anthocyanins, the colored water-soluble pigments, have increasingly drawn the attention of researchers for their novel applications. The sources of anthocyanin are highly diverse, and it can be easily extracted. The unique biodiversity of the Himalayan Mountain range is an excellent source of anthocyanin, but it is not completely explored. Numerous attempts have been made to study the phytochemical aspects of different Himalayan plants. The distinct flora of the Himalayas can serve as a potential source of anthocyanins for the food industry. In this context, this review is an overview of the phytochemical studies conducted on Himalayan plants for the estimation of anthocyanins. For that, many articles have been studied to conclude that plants (such as Berberis asiatica, Morus alba, Ficus palmata, Begonia xanthina, Begonia palmata, Fragaria nubicola, etc.) contain significant amounts of anthocyanin. The application of Himalayan anthocyanin in nutraceuticals, food colorants, and intelligent packaging films have also been briefly debated. This review creates a path for further research on Himalayan plants as a potential source of anthocyanins and their sustainable utilization in the food systems. Full article

Surface cracks are typical defects in high-speed rail (HSR) slab tracks, which can cause structural deterioration and reduce the service reliability of the track system. However, the question of how to effectively detect and quantify the surface cracks remains unsolved at present. In this paper, a novel crack-detection method based on infrared thermography is adopted to quantify surface cracks on rail-track slabs. In this method, the thermogram of a track slab acquired by an infrared camera is first processed with the non-subsampled contourlet transform (NSCT)-based image-enhancement algorithm, and the crack is located via an edge-detection algorithm. Next, to quantitatively detect the surface crack, a pixel-locating method is proposed, whereby the crack width, length, and area can be obtained. Lastly, the detection accuracy of the proposed method at different temperatures is verified against a laboratory test, in which a scale model of the slab is poured and a temperature-controlled cabinet is used to control the temperature-change process. The results show that the proposed method can effectively enhance the edge details of the surface cracks in the image and that the crack area can be effectively extracted; the accuracy of the quantification of the crack width can reach 99%, whilst the accuracy of the quantification of the crack length and area is 85%, which essentially meets the requirements of HSR-slab-track inspection. This research could open the possibility of the application of IRT-based track slab inspection in HSR operations to enhance the efficiency of defect detection. Full article

Although various studies have investigated biochar (BC) soil amendments for improving soil microbial abundance, functions, and community structure, a comparison of dairy manure biochar (MBC) to wood biochar (WBC) is warranted given the large volume of manure produced in high-intensity dairy production. Additionally, the synergistic effects of different BC sources and loading percentages on microbial functions and community composition using massively parallel 16S DNA sequencing in BC-amended soils with different types of crops are limited. In this study, the synergistic effects of BC type, BC loading percentage, and crop types on soil fertility, prokaryote community diversity, and functions were investigated in a greenhouse study. The MBC and WBC were used to amend sandy loam soils at increasing BC loading percentages (0, 5, and 10%) to grow the cool-season forages crimson clover (Trifolium incarnatum; an annual legume) and Italian ryegrass (Lolium multiflorum Lam.; an annual forage grass) for 120 days. High nutrient concentrations in MBC shifted microbial communities towards r-strategists and alkaliphiles, potentially increasing the rate of nutrient bioremediation from high nitrogen- and phosphorus-containing soil amendments. This study enables emerging biochar agronomic use recommendations with different crops. Full article

Maternal infection with Zika virus (ZIKV) is associated with a distinct pattern of birth defects, known as congenital Zika syndrome (CZS). In ZIKV-exposed children without CZS, it is often unclear whether they were protected from in utero infection and neurotropism. Early neurodevelopmental assessment is essential for detecting neurodevelopmental delays (NDDs) and prioritizing at-risk children for early intervention. We compared neurodevelopmental outcomes between ZIKV-exposed and unexposed children at 1, 3 and 4 years to assess exposure-associated NDD risk. A total of 384 mother–child dyads were enrolled during a period of active ZIKV transmission (2016–2017) in Grenada, West Indies. Exposure status was based on laboratory assessment of prenatal and postnatal maternal serum. Neurodevelopment was assessed using the Oxford Neurodevelopment Assessment, the NEPSY^® Second Edition and Cardiff Vision Tests, at 12 (n = 66), 36 (n = 58) and 48 (n = 59) months, respectively. There were no differences in NDD rates or vision scores between ZIKV-exposed and unexposed children. Rates of microcephaly at birth (0.88% vs. 0.83%, p = 0.81), and childhood stunting and wasting did not differ between groups. Our results show that Grenadian ZIKV-exposed children, the majority of whom were without microcephaly, had similar neurodevelopmental outcomes to unexposed controls up to at least an age of 4 years. Full article

Gnomoniopsis smithogilvyi (Gs) is a relevant pathogen of chestnut since it provokes significant losses worldwide. The aim of this study was to screen the effect of a new biocontrol agent (BCA) against Gs isolated from chestnut (CIMO-BCA1) on the mould’s growth as well as on the production of secondary metabolites. The chemical fungicide Horizon^® (tebuconazole; HOR) and the commercial biofungicide Serenade^® ASO (Bacillus amyloliquefaciens QST 713; ASO) were also tested. Three concentrations of each antifungal (HOR, ASO, and CIMO-BCA1) were faced with Gs in the growth study in a chestnut-based medium. The intermediate concentrations were used for the analyses of metabolites by LC-MS/MS. CIMO-BCA1 was also identified as B. amyloliquefaciens. All agents reduced the mould’s growth, and the CIMO-BCA1 treatment with an intermediate concentration was the most effective. The metabolite analysis revealed, for the first time, the production of two mycotoxins by Gs, including 3-nitropropionic acid and diplodiatoxin. Additionally, HOR stimulated the production of diplodiatoxin. In conclusion, Gs could present a health risk for consumers. B. amyloliquefaciens strains effectively decreased the mould’s growth, but they must be applied at effective concentrations or in combination with other strategies to completely reduce the hazard. Full article

Multidrug resistance (MDR) proteins belonging to the ATP-Binding Cassette (ABC) transporter group play a crucial role in the export of cytotoxic drugs across cell membranes. These proteins are particularly fascinating due to their ability to confer drug resistance, which subsequently leads to the failure of therapeutic interventions and hinders successful treatments. One key mechanism by which multidrug resistance (MDR) proteins carry out their transport function is through alternating access. This mechanism involves intricate conformational changes that enable the binding and transport of substrates across cellular membranes. In this extensive review, we provide an overview of ABC transporters, including their classifications and structural similarities. We focus specifically on well-known mammalian multidrug resistance proteins such as MRP1 and Pgp (MDR1), as well as bacterial counterparts such as Sav1866 and lipid flippase MsbA. By exploring the structural and functional features of these MDR proteins, we shed light on the roles of their nucleotide-binding domains (NBDs) and transmembrane domains (TMDs) in the transport process. Notably, while the structures of NBDs in prokaryotic ABC proteins, such as Sav1866, MsbA, and mammalian Pgp, are identical, MRP1 exhibits distinct characteristics in its NBDs. Our review also emphasizes the importance of two ATP molecules for the formation of an interface between the two binding sites of NBD domains across all these transporters. ATP hydrolysis occurs following substrate transport and is vital for recycling the transporters in subsequent cycles of substrate transportation. Specifically, among the studied transporters, only NBD2 in MRP1 possesses the ability to hydrolyze ATP, while both NBDs of Pgp, Sav1866, and MsbA are capable of carrying out this reaction. Furthermore, we highlight recent advancements in the study of MDR proteins and the alternating access mechanism. We discuss the experimental and computational approaches utilized to investigate the structure and dynamics of MDR proteins, providing valuable insights into their conformational changes and substrate transport. This review not only contributes to an enhanced understanding of multidrug resistance proteins but also holds immense potential for guiding future research and facilitating the development of effective strategies to overcome multidrug resistance, thus improving therapeutic interventions. Full article

This study investigated the flexural behavior of prefabricated RC bridge decks with different joint materials, normal strength concrete or UHPC (normal strength concrete for RC deck, while UHPC means ultra-high performance concrete). A total of three specimens were tested and subjected to four-point bending loads. The load–deflection curve, strain curve, load–crack width curve, and failure mode were analyzed. Numerical models with cohesive models were built and verified with test results to explore the force-transferring mechanism. The results show that UHPC effectively improved the crack strength, flexural strength, and failure mode. Compared with the joint with normal-strength concrete, the crack strength and flexural strength increased by 66.7% and 6%, respectively. The failure mode of the specimen with UHPC as joint material changed from a concentrated cracking failure of the joint to a multi-crack development failure. The behavior of the specimen with UHPC as joint material was similar to the monolithically cast specimen. In addition, the application of the current design method was evaluated and compared with test results. Full article