Precise individual tree or sample-based inventories derived from 3D point cloud data of mobile laser scanning can improve our comprehensive understanding of the structure, function, resilience, biodiversity, and ecosystem services of urban forests. This study assessed the performance of a hand-held laser scanning system for the extraction of tree position, diameter at breast height (DBH) and tree height (H) in an urban area. A total of 2083 trees of 13 species from 34 plots were analyzed. The results showed that the registration of tree positions using ground control points (GCPs) demonstrated high accuracy, with errors consistently below 0.4 m, except for a few instances. The extraction accuracy of DBH for all trees and individual species remained consistently high, with a total root mean square error (RMSE) of 2.06 cm (6.89%) and a bias of 0.62 cm (2.07%). Notably, broad-leaved trees outperformed coniferous trees, with RMSE and bias values of 1.86 cm (6%) and 0.76 cm (2.46%) compared to 2.54 cm (9.46%) and 0.23 cm (0.84%). Tree height extraction accuracy varied significantly among different species, with R2 values ranging from 0.65 to 0.92. Generally, both DBH and height were underestimated. Linear mixed effects models (LME) were applied to evaluate factors affecting the performance of HLS with the plot as a random factor. LME analysis revealed that plant type and terrain significantly influenced the accuracy of DBH and H derived from HLS data. Other fixed factors of plot area, tree density and trajectory length didn’t have significance. With a large sample size, we concluded that the HLS demonstrated sufficient accuracy in extracting individual tree parameters in urban forests.

German noise action plans aim to reduce negative health outcomes from noise exposure and identify quiet areas free of noise pollution. Quiet area identification in German noise action plans is based primarily on noise mapping and spatial analysis and not empirical or qualitative data about acoustic environments, thus leaving a gap in the understanding of the quality of formally recognized quiet areas in noise action plans. This work presents a comparative empirical case study in Dortmund, Germany, with the aim to describe the diurnal dB(A) and biophonic properties of quiet areas versus noise 'hot spots'. Sound observations were collected (n=282,764) in five different natural or recreational land use patch types larger than four acres within 33 proposed quiet areas in Dortmund (n=70) and 23 noise hot spots between April 27^th, 2022 and March 2^nd, 2023. We find that quiet areas are on average more than 20 dB(A) quieter than noise hot spots almost every hour of the day. Forests, managed tree stands, cemeteries, and agriculture diel patterns are dominated by dawn dusk chorus in spring and summer, whereas sport and recreation as well as noise hot spots are dominated by traffic and human noise. A novel composite biophony mapping procedure is presented that finds distinct temporal distribution of biophony in forested and agriculture peri-urban locations positively associated with patch size, distance away from LDEN > 55, proximity to water, and the number of vegetation layers in the plant community. Anthrophony distribution dominates urban land uses in all hours of the day, but expands during day and evening and contracts at night and in dusk hours. The procedures presented here illustrate how qualitative information regarding quiet areas can be integrated into German noise action planning.

Indole and indole-3-lactate are known dominant microbial tryptophan catabolites (MICT). In obesity, the fecal indole concentration corresponds to the normal one, and that of indole-3-lactate significantly decreases along with other MICT, while it increases in blood plasma. During the analysis of the «enzymatic landscape» of the intestinal microbiota we find an almost twofold increase in the correlation between the concentrations of fecal MICT and the «enzymatic landscape», with indole-3-lactate having the closest relationships with the “enzymatic landscape” of all MICT. Here, we report statistically significant correlations of indole-3-lactate and the gut microbial enzymes for fructose, amino sugars, nucleotides, polyamines metabolism, and sulfoglycolysis. We also demonstrate that indole-3-lactate producing microbiota representatives increase three-fold in obesity. The phenotype of the microbiotic population is thus represented by completely different genera and species of microorganisms in obese individuals compared to healthy donors.

Extraction techniques of important bioactive molecules from the major concern of Seafood byproducts are getting emphasis for better valorization. Employing green extraction technologies for efficient and quality production of these bioactive molecules is also strictly required. Hence, understanding the extraction process parameters to effectively design an applicable optimization strategy could make this real. In this review, statistical optimization strategies applied for the extraction process parameters of bioactive molecules from Seafood byproducts are focused. The type of experimental designs, and techniques applied to criticize and validate the effects of independent variables on the extraction output was addressed. Dominant parameters studied were enzyme/substrate ratio, pH, time, temperature and power of extraction instruments. The yield of bioactive compounds, chitin and chitosan, proteins and peptides, enzymes and carotenoids (Astaxanthins) were the most studied responses. Efficiency and/or economic and quality considerations and their selected optimization strategies that favour the production of potential bioactive molecules were also reviewed.

During public health events, Active Mobility (walking and cycling) plays an important role in securing residents' travel. To enhance the resilience of urban transportation, this article integrates the travel environment elements for walking and cycling and constructs a travel environment for Active Mobility evaluation index system. This article uses survey data from the main urban area of Harbin in the context of the COVID-19 pandemic in May 2022, and combines the Gradient Boosting Decision Tree (GBDT) and Impact-Asymmetry Analysis (IAA) methods to analyze the satisfaction of the travel environment for Active Mobility. It proposes strategies for optimizing the travel environment for Active Mobility, ensuring residents' travel during public health events, guiding them to adopt Active Mobility, and improving urban transportation resilience. This research shows that Active Mobility can enhance urban transportation resilience. In addition, there are differences in resident demand for walking and cycling environments in the travel environment for Active Mobility. Residents are more concerned about the comfort of the walking environment, while they prioritize the convenience of the cycling environment.

Children are inherently curious about everything they encounter, making the early years a perfect time for STEAM (science, technology, engineering, arts, and math) investigations. An outdoor learning environment can influence STEAM concept formation of preschoolers with intentional design that offer STEAM learning affordances. Despite the rising interest in early STEAM education, there is still limited literature on how the outdoor environment may influence STEAM learning behaviors of preschoolers (3-5 years old). This scoping review intends to evaluate the existing knowledge regarding the physical factors that contribute to STEAM learning affordances in an outdoor environment for children aged 3 to 5. The review included studies from the last twenty years. This scoping review was conducted in accordance with the criteria outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). For this scoping review, 843 citations were discovered across four databases (JSTOR, Scopus, EBSCOhost, and Web of Science), ProQuest, and Google Scholar, and 31 articles were considered eligible for inclusion. Through the synthesis of information from those 31 studies, a list of STEAM learning behaviors of children and STEAM activity-supportive settings were identified that may positively influence preschoolers' STEAM concept development.

How hands-on gardening impacts behaviors including healthy eating and physical activity during early childhood can be of critical importance for preventing early onsets of obesity. This research investigates how participating in hands-on gardening impacts preschoolers’ (3-5 years old) physical activity (measured by accelerometers) in childcare centers in the Semi-Arid Climate Zone. The research was conducted in eight licensed childcare centers located in West Texas with 149 children (n=149). Four childcare centers in the experimental group received hands-on garden interventions; the other four in the control group did not. In both experimental (intervention) and control (non-intervention) centers, children wore Actigraph GT3X+ accelerometers continuously for 5 days before and for 5 days after intervention (a total of 10 days). Results show that the duration of sedentary behavior of children in the experimental (intervention) group significantly decreased compared to children in the control (non-intervention) group. The finding suggests that the positive effects of childcare hands-on gardening on physical activity extend to semi-arid climate zones where gardening is challenging due to high temperatures and lack of annual rainfall. The research emphasizes the critical need to incorporate hands-on gardening in childcare centers as an obesity prevention strategy nationally in the U.S. and beyond.

Urban environments face escalating challenges, e.g. due to uncontrolled urbanization, rapid population growth or climate changes, prompting the exploration of sustainable solutions for enhancing urban green spaces (UGS). For this reason, poplars (Populus L.), due to their rapid growth, wide range adaptability to environmental conditions and versatility of use, would have emerged as very promising. This comprehensive review synthesizes current knowledge regarding poplar's application in urban landscapes, emphasizing its multifaceted contributions and benefits. However, challenges arise from the variable lifespans of different poplar cultivars, necessitating strategic management approaches. Selecting cultivars based on growth rates, root system characteristics, and adaptability to urban conditions is pivotal. Adaptive replanting strategies, incorporating species with varying lifespans, offer solutions to maintain continual greenery in urban landscapes. Collaborative efforts between researchers, urban planners, and policymakers are essential for devising comprehensive strategies that maximize benefits while addressing challenges associated with their variable lifespans. In conclusion, harnessing poplar's potential in urban greenery initiatives requires a balanced approach that capitalizes on their benefits while mitigating challenges. Further research and adaptive strategies are crucial for sustained and effective utilization in creating resilient and vibrant urban landscapes.

Historically, urban development has always been centered on coastal areas – with access to waterbodies – seas, rivers and canals being a significant advantage for movement and trade. With most of the world’s megapolises located on coasts, land reclamation offers a solution for the expansion of city centers which are otherwise restricted by the coastline. The current understanding of urban regeneration and development on reclaimed lands is defined in this study, answering the basic questions of what, why and how. This study aims to assess the urban regeneration on reclaimed coastal land based on the principles of sustainable development defined by existing studies. The literature review establishes a theoretical framework and defines performance-based benchmarks identifying the spatial indicators of urban development. Composite indicators namely open space coverage, land use mix, percentage of coast for people, accessibility to public transportation and amenities, availability of pedestrian paths and cycling tracks and adequate road networks are considered for this framework. The conclusions are drawn based on the results of the analysis of spatial layout using GIS as a tool to map and empirically measure each indicator. The framework is validated using a major land reclamation project, West Bay, in the coastal urban area of ​​the city of Doha. The results determine that West Bay has achieved a good level of sustainability, although there are areas that could be enhanced to further improve the overall sustainability of urban development. These findings can serve as a guide for policymakers and various stakeholders for sustainable urban planning on reclaimed coastal lands.

Urban lakes, especially those of natural origin, provide ecosystem services, recreation being one of the most important and highly valued by the city dwellers. Fulfilling the needs of city residents to relax and have contact with nature has become a priority in urbanized areas and has been proved to positively affect people’s health and well-being. The recreational potential of water bodies was identified to be most important aspect of ecosystem services to the residents of the neighboring areas. An assessment of recreational ecosystem services (RES) provisioning to society based on the real time spent by the citizens and housing values in the rural-urban gradient revealed that the economic benefits of lakes differ in urbanized, suburban and rural landscapes. The growth of cities has led to an increased population density in the surroundings of ecologically valuable areas, resulting in higher pressure from visitors seeking recreational areas. Along with urbanization, the impoverishment of ecosystem functions takes place, limiting their capability to provide ecosystem services. In this work provisioning of recreational ecosystem services of 28 floodplain lakes located along the urban-rural gradient of the Warsaw agglomeration was assessed. The relationship between the ecological value of the water bodies, measured using naturalness indices, and the recreational ecosystem services they can provide was assessed. The results showed that the floodplain lakes located along the urban-rural gradient are of a great importance to the citizens due to their recreational potential. The provisioning of recreational ecosystem services is poorly connected with the ecological characteristics of the floodplain lakes. Only hemeroby, was significantly correlated with provisioning, and there was no relationship with factors such as naturalness of vegetation or water quality, demonstrating that public preference was not generally influenced by high ecological quality. These data should be available to potential buyers and be integrated in spatial planning management plans in order to shape future housing policy.

This literature review paper delves into the synergies between Climate-Smart Agriculture (CSA) and the effective management of food losses. With the escalating challenges posed by climate change and the pressing need to address food security concerns, the intersection of these two critical domains becomes paramount for sustainable agricultural practices. The review explores existing research on the implementation of climate-smart agricultural techniques and their impact on mitigating food losses throughout the agricultural value chain. The paper synthesizes findings related to climate-resilient crop varieties, precision farming, water-use efficiency, and sustainable soil management, highlighting their contributions to reducing post-harvest losses and enhancing overall food security. In addition to summarizing current knowledge, this paper identifies gaps in the literature and proposes avenues for future research. This review serves as a foundation for researchers, policymakers, and practitioners seeking to contribute to the advancement of climate-smart agriculture and the reduction of food losses, paving the way for a more sustainable and resilient global food system.

Fibrodysplasia Ossificans Progressiva (FOP) is an enigmatic, ultra-rare genetic disorder characterized by progressive heterotopic ossification, wherein soft connective tissues undergo pathological transformation into bone structures. This incapacitating process severely limits patient mobility and poses formidable challenges for therapeutic intervention. Predominantly caused by missense mutations in the ACVR1 gene, the disorder has hitherto defied comprehensive mechanistic understanding and effective treatment paradigms. This write-up offers a comprehensive overview of the contemporary understanding of FOP's complex pathobiology, underscored by advances in molecular genetics and proteomic studies. We shed light on targeted therapy, spanning genetic therapeutics, enzymatic and transcriptional modulation, stem cell therapies, and innovative immunotherapies. We also focused on the intricate complexities surrounding clinical trial design for ultra-rare disorders like FOP, addressing fundamental statistical limitations, ethical conundrums, and methodological advancements essential for the success of interventional studies. We advocate for the adoption of a multi-disciplinary approach that converges bench-to-bedside research, clinical expertise, and ethical considerations to tackle the challenges of ultra-rare diseases like FOP and comparable ultra-rare diseases. Overall, this article serves a dual role: as a definitive scientific resource for ongoing and future FOP research and as a call to action for innovative solutions to address methodological and ethical challenges that impede progress in the broader field of medical research for ultra-rare conditions.

Transdermal alcohol biosensors have the ability to detect the alcohol that emanates from the bloodstream and diffuses through the skin. However, they have suffered from long-term fouling of the sensor element and drift in the resulting sensor readings over time. Here, we report a disposable cartridge platform that solves the problem of sensor fouling, and an enzymatic detection pathway that minimizes baseline drift for sensitive detection. Laboratory characterization of the enzymatic alcohol sensor demonstrates a linear sensor range of between 0 and 50 mM. Further, we show continuous transdermal alcohol data recorded with a human subject over 48 hours.

Elevated carbon dioxide (eCO₂) stimulates wheat grain yield, but simultaneously reduces protein (N) concentration. Also other essential nutrients are subject to change. This study is a comprehensive synthesis of wheat experiments with eCO₂, estimating effects on N, minerals (B, Ca, Cd, Fe, K, Mg, Mn, Na, P, S, Zn), and starch. Analysis was made by i) deriving response functions for the relative effect on element concentration in relation to CO₂ concentration, ii) meta-analysis to test the magnitude and significance of observed effects, and iii) relating CO₂ effects on minerals to effects on N and grain yield. Responses range from zero to strong negative effects of eCO₂ on mineral concentration, with largest reductions for the nutritionally important elements N, Fe, S, Zn and Mg. Together with the positive but small and non-significant effect on starch concentration, the large variation in effects suggests that CO₂-induced responses cannot be explained by a simple dilution model. To explain the observed pattern, uptake and transport mechanisms may have to be considered, along with the link of different elements to N uptake. Our study shows that eCO₂ has a significant effect on wheat grain stoichiometry, with implications for human nutrition in a world of rising CO₂.

Analyses of the three predominant types of sedimentation – clastic, carbonate and black shale – revealed their discontinuity/continuity in different facies environments of the Middle and Late Devonian of the central part of the Volga-Urals petroleum province, namely (1) in depressions, both condensed and non-condensed, (2) on the slopes of depressions and (3) in shallow water environments represented by tectonic arches or localised biohermal uplifts. The regional zonation of conodonts, correlated with the global chronostratigraphic scheme, substantiates the stratigraphic completeness of the general Devonian sequence in this area. In particular, the sedimentation of organic-rich black shales, traditionally considered as source rocks, lasted more than 29 million years, starting from the Late Eifel and ending at the Devonian-Carboniferous boundary. There was only one hiatus in the deposition of both black shales and carbonate sediments, lasting about 2.5 million years at the end of the Frasnian. That interval is dominated by clastic sediments, which are considered to be the most productive reservoirs of the Volga-Ural province. In the time interval from the beginning of the Eifel to the end of the Frasnian (about 17 Ma), (a) clastic sediments show the highest accumulation rates; (b) the most complete sequences occur in depressions; and (c) arches and uplifts show the most significant gaps in the geological record. During Famennian, (a) clastic sedimentation has completely ceased; (b) differences between the slopes of troughs and shallow-water environments have diminished, resulting in stable accumulation of carbonate sediments in both settings; (c) the decrease in sequence thickness (up to 50 m) in depressions suggests reduced accumulation rates of deep-water organic-rich black shales. The results help to understand the complex spatial relationship between different coexisting sedimentation types and focus attention to the incompleteness of the geological record in different environments.

Separase is a key cysteine protease to separate sister chromatids through digestion of cohesion ring that inhibits chromosome segregation as trigger of metaphase–anaphase transition in eukaryotes and highly regulated its activity by binding with securin and cyclinB-CDK1 complex. Those bindings prevent proteolytic activity of separase until the onset of anaphase. Chromosome missegregation and aneuploidy are frequently observed in malignancies. However, there are some difficulties for biochemical examinations due to instability of separase in vitro and a few spatiotemporal resolution approaches monitoring live separase activity throughout mitotic processes. Here we have developed FRET-based molecular sensors including GFP variants with separase cleavable sequences as donor and covalently attached fluorescent dye as acceptor molecules applicable to conventional live cell imaging and flow cytometric analysis because of efficient live cell uptake. We investigated performance of equivalent molecular sensors localized or not localized inside nucleus under cell cycle control using flow cytometry. Synchronized cell cycle progression rendered significant separase activity detections in both molecular sensors. We obtained consistent outcomes with localized molecular sensor introduction and cell cycle control by fluorescent microscopic observations. We thus established live cell separase activity monitoring systems specifically or statistically that could lead to elucidate separase properties in detail.

The human landscape transforming activity contributes to the global change of vegetation in different forms. Hunting is one of the most ancient human landscape-shaping activities. Feeders for hunting are particularly disruptive to vegetation. In the present study, we conducted a vegetation survey in these highly disturbed places. We are investigating the vegetation dynamics over several years in in the turkey oak–sessile oak zone, in two areas with different moisture and shade conditions (forest and clearing). One important background factor is changes in precipitation and temperature. The novelty of our present study lies in the fact that the observation takes place with continuous disturbance, where the human influence is very large. Our results confirm that the weed infestation be detectable at bait sites over a long period, and the interannual changes were typical in every year, according to the fact that in August, more weed species are usually present with a greater cover at the bait sites. The main meteorological factors played a role in the degree of weed infestation in each year. There was a higher proportion of vegetation regeneration in wetter years, while dry periods do not favor successional processes. With the drying of the climate, the disturbed areas are constantly losing their natural value, but wetter weather is not an automatic solution either. A more precise understanding of vulnerable systems and careful planning of treatment interventions is necessary.

Lignocellulosic biomass has garnered attention as an abundant and sustainable alternative energy source that can facilitate reliable and environmentally friendly energy generation. Energy security improves, and environmental impacts diminish when bioethanol, a biofuel produced via lignocellulose-based processes, is utilized. The lignocellulosic biomass of Thysanolaena latifolia has considerable potential as a bioethanol feedstock due to its high carbohydrate content (62.4 ± 0.7%). In this study, feedstock derived from T. latifolia was pretreated with various concentrations of H3PO4 to determine the ideal conditions for enzymatic hydrolysis to convert the feedstock to fermentable sugar. The findings revealed that hydrolysis efficiency and glucose recovery yields were substantially improved compared to those of the untreated sample. Pretreated samples were enzymatically digested to produce a liquid hydrolysate. This hydrolysate was fermented without detoxification using Saccharomyces cerevisiae TISTR 5339 to produce ethanol. The results indicated that T. latifolia biomass hydrolysate is a promising long-term carbon source for ethanol production from cellulosic biomass. Furthermore, the morphological and crystallographic characteristics of the treated T. latifolia biomass were influenced by H3PO4 concentration, as indicated by the SEM images, X-ray diffractogram patterns, and crystallinity index values. Therefore, utilizing T. latifolia feedstock to produce bioethanol can enhance bioenergy sustainability.

Timely and accurate information on tree species is crucial for the sustainable management of natural resources, forest inventory, biodiversity detection, and carbon stock calculation. The advancement of remote sensing technology and artificial intelligence has facilitated the acquisition and analysis of remote sensing data, resulting in more precise and effective classification of tree species. Multimodal remote sensing data and deep learning seem to be the current tree species classification research mainstream, whether or not. The current review on the remote sensing data and deep learning tree species classification methods perspectives to analyze the unimodal and multimodal remote sensing data and classification methods in this realm is missing. To bridge the gap, we search for major trends in the remote sensing data and tree species classification methods, provide a detailed overview of classic deep learning-based methods for tree species classification, and discuss the limitations.

Analyzing BRCA1/2 tumor pathogenic variants (TPVs) in epithelial tubal/ovarian cancers (EOC) has become an essential part of the diagnostic workflow in many centers to guide treatment options and genetic cascade testing. However, there is no standardization of testing procedures, including techniques, gene assays, or sequencers used, and data on the execution of tumor tests remains scarce. Therefore, we evaluated characteristics of BRCA1/2 tumor testing in advanced-stage EOC with real-world national data. Pathology reports of patients diagnosed with EOC in 2019 in the Netherlands were obtained from the Dutch Pathology Registry (PALGA), and data regarding histological subtype and BRCA1/2 tumor tests were extracted. A total of 999 patients with advanced-stage EOC were included. Tumor tests were performed for 502 patients (50.2%) and BRCA1/2 TPVs were detected in 14.7%. Of all tests, 48.6% used hybrid capture techniques and 26.5% used PCR-based techniques. More than half of the tests (55.0%) analyzed other genes in addition to BRCA1/2. Overall, this study highlights the heterogeneity in the execution of BRCA1/2 tumor tests. Despite a lack of evidence of quality differences, we emphasize that adequate reporting and internal and external quality monitors are essential for high-quality implementation and execution of reliable BRCA1/2 tumor testing, which is crucial for identifying all patients with BRCA1/2 TPVs.

Self-assembled structures mostly arises through enzyme-regulated phenomena in nature under persistent conditions. Enzymatic reactions are one of main biological processes in fabrication and construction of supramolecular hydrogel networks required for biomedical applications. The enzymatic processes provide a unique opportunity to integrate hydrogel formation. In most of cases, structure and substrates of hydrogels are adjusted by enzyme catalysis due to the chemo-, regio- and stereo-selectivity of enzymes. Hydrogels processed by using various enzyme schemes showed remarkable characteristics as dynamic frames for cells, bioactive molecules and drugs in biomedical applications. A novel class of enzyme-mediated crosslinking hydrogels mimics the extracellular matrices by displaying unique physicochemical properties and functionalities like water-retention capacity, drug loading ability, biodegradability, biocompatibility, biostability, bioactivity, optoelectronic properties, self-healing ability, shape memory ability. In recent years, many enzymatic systems investigated hydrogel cross-linking. Results of biocompatible hydrogel products show that these mechanisms of crosslinking can fulfill requirements for variety of biomedical applications including tissue engineering, wound healing and drug delivery.

Intrinsically Disordered Proteins (IDPs) play crucial roles in signal transduction, cell differentiation, and transcriptional regulation. Many disrupted genes associated with mental disorders are identified as IDPs, and emerging evidence suggests the functional role of IDPs in neuropsychiatric disorders. However, few studies comprehensively explore the functional association between protein disorder properties and different mental diseases. To address this gap, we collected disrupted gene sets for seven mental diseases (MDD, SCZ, BP, ID, AD, ADHD, ASD) and a control gene set from normal brains using DisGeNET and GeneCards databases. The state-of-the-art predictor IUPred2A was then utilized to calculate the disorder properties , followed by a thorough comparison between the disordered proteins in mental diseases and healthy controls. Functional enrichment analysis and protein-protein interaction networks were conducted to investigate the IDPs’ functional roles in psychiatric diseases. Additionally, we demonstrated the role of IDPs in protein binding formations through a case study of alpha-synuclein using protein docking. Our findings reveal that differentially expressed proteins in mental disorders, especially in ASD and ADHD, exhibit more IDPs than those in healthy controls. IDPs in psychiatric disorders are significantly enriched in neurodevelopmental pathways and play an important role in in gene expression regulation. Our results indicate distinct functional patterns of disorder proteins among mental diseases and healthy controls. When comparing the IDPs between ASD and ADHD, we observed that IDPs in ADHD are more likely linked to the synaptic signaling and regulation, while IDPs in ASD are more tendentiously related to diverse and complex biological processes. Our work offers valuable insights into the important functions of IDPs in psychiatric disorders, enhancing our understanding of the molecular mechanisms involved in psychiatric disorders.

Bioelectrocatalysis has become one of important research fields in electrochemistry and provided a firm base for an important technology for application to various bioelectrochemical devices such as biosensors, biofuel cells, and biosupercapacitors. The understanding and technology in bioelectrocatalysis have been greatly improved by introducing nanostructured electrode materials and protein-engineering methods over the last few decades. Recently, the electro-enzymatic production of renewable energy resources and useful organic compounds (bioelectrosynthesis) also attracts worldwide attention. In this review, we summarize recent progress in applications of enzymatic bioelectrocatalysis.

The main function of dUTPases is to regulate the cellular levels of dUTP and dTTP, thereby playing a crucial role in the DNA repair mechanisms. Despite the fact that mutant organisms with the obliterated dUTPase enzymatic activity remain viable, it is not possible to knockout the dut gene completely due to the lethal consequences of such mutation for the organism. As a result, it is considered that this class of enzymes perform an additional function that is essential for the organism's survival. In this study, we provide the evidence that the dUTPase of bacteriophage T5 possesses supplemental function in addition to its canonical role. We determined the crystal structure of bacteriophage T5 dUTPase with a resolution of 2.0 Å, and discovered a distinct short loop, consisting of 6 amino acid residues which represents unique structural feature specific to the T5-like phages dUTPases. The removal of this element did not affect the overall structure of the homotrimer, but had significant effects on the development of the phage. Furthermore, it has been shown that the enzymatic function and the novel function of bacteriophage T5 dUTPase are unrelated and independent from each other.

Paper recycling has increased in recent years. A principal consequence of this process is the problem of addressing polymeric components known as stickies. A deep characterization of stickies sampled over one year in a recycled paper industry in México was performed. Based on their chemical structure, an enzymatic assay was performed using lipases. Compounds found in stickies by Fourier-Transform Infrared spectrometry were poly (butyl-acrylate), dioctyl phthalate, poly (vinyl-acetate), and poly (vinyl-acrylate). Pulp with 4% consistency and pH=6.2 was sampled directly from the mill once macro stickies were removed. Stickies were quantified by counting the tacky macrostructures in the liquid fraction of the pulp using a Neubauer chamber before the paper was made, and they were analyzed with rhodamine dye and a UV lamp. Of the two enzymes evaluated, the best treatment condition used Lipase 30G at a concentration of 0.44 g/L, which produced a 35.59% decrease in stickies. SebOil DG showed a smaller stickies reduction of 21.5% when used at a concentration of 0.33 g/L. Stickies in kraft paper processes were actively controlled by the action of lipases, and future research should focus on how this enzyme recognizes its substrate and should apply synthetic biology to improve lipase specificity.

Nanocellulose has gained increasing attention during the past decade, which is related to its unique properties and wide application. In this paper, nanocellulose was produced by hydrolysis with ionic liquids (1-ethyl-3-methylimidazole acetate (EmimOAc) and 1-allyl-3-methylimidazolium chloride (AmimCl)) from microcrystalline cellulose (Avicel and Whatman) subjected to enzymatic pretreatment. The obtained material was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), scanning electron microscope (SEM) and thermogravimetric analysis (TG). The results showed that the nanocellulose had a regular and spherical structure with a diameter of 30-40 nm and exhibited lower crystallinity and thermal stability than the material after hydrolysis with Trichoderma reesei enzymes. However, the enzyme-pretreated Avicel had a particle size of about 200 nm and a cellulose II structure. A two-step process involving enzyme-pretreatment and hydrolysis with ionic liquids resulted in the production of nanocellulose. Moreover, the particle size of nanocellulose and its structure depend on the ionic liquid used.

By analyzing the urban landscape, this investigation focuses on commercial typologies in historical urban areas and its relationship with the urban landscape and its heritage values. Trade plays an essential role in historical urban areas, both in the past and in the present, since it is part of the urban landscape—creating it and modifying it, but also preserving it. Historical protected urban areas contain diverse elements reflecting the impacts of commercial activities that have existed in cities throughout history. At present, the urban landscape of commercial activity is made up of a multiplicity of typologies and formats which interact with the historical landscape and its values, using them to strengthen its strategies of attraction, differentiation, and sales. Shop owners contribute to the preservation of historic urban areas by maintaining the commercial functions within them. Therefore, we affirm that the role of commercial activity in the preservation of urban protected areas is essential. However, further research is needed because this aspect has not been addressed in depth by the scientific community specializing in the management of cultural heritage.

Soy isoflavones are considered important sources of bioactive compounds, but they are poorly absorbable, due to their large hydrophilic structures. Some biotransformation strategies have been used to convert the glycosidic form into aglycones, making them available for absorption. This study evaluated the potential of enzymatic and/or microbial fermentation bioprocesses in soymilk extract before and after gastrointestinal in vitro digestion. Commercial β-glucosidase and mix of commercial probiotics containing Lactobacillus acidophilus, L. casei, Lactococcus lactis, Bifidobacterium bifidum e B. lactis were used to biotransform soymilk extract. Isoflavone profile was quantified by HPLC-DAD, total phenolic content by Folin–Ciocalteu test, and antioxidant capacity by ORAC and FRAP. Soymilk enzymatically treated (ET) followed by microbial fermentation (ET+F) resulted in the conversion of glycosylated isoflavones (6-fold lower than control for daidzin and 2-fold for genistin) to aglycones (18-fold greater than control for dadzein and genistein), besides to increase the total phenolic content (3.48 for control and 4.48 mg/ml ET+F) and to improve antioxidant capacity represented by the ORAC (120 for control and 151 mg/ml ET+F) and by the FRAP (285 for control and 317 µl/ml for ET+F) before in vitro digestion. Further, the digested ET+F samples resulted a higher content of genistein (2-fold higher than control) also an increase in the total phenolic content (2.81 for control and 4.03 mg/ml for ET+F) and antioxidant capacity by ORAC were greater compared to undigested samples. In addition, the microbial fermentation process isolated also resulted in the positive effects, but de combination of ET followed by F presented a synergistic effect, suggesting the greater potential for both bioprocesses to contribute to functional and nutritional properties on fermented soy-based products.

The current study emphasizes on optimizing a suitable ratio of enzymatically hydrolyzed potato powder (EHPP) and whole milk powder (WMP) to produce a quality yogurt by evaluating the physicochemical and rheological properties. The results showed that the addition of EHPP decreased the pH towards acidic conditions which resulted in the high acidity of yoghurt. The proximate composition showed that EHPP increased the ash, protein, water holding capacity (WHC) while fat, synersis, color parameters and total solid were decreased when compared to control yoghurt (CY) sample. Moreover, texture profile (TPA) analysis showed that the addition of EHPP decreased the hardness and cohesiveness while springiness did not show significant difference. Furthermore, rheological properties revealed that EHPP decreased the storage modulus (G’) and loss modulus (G”) when compared with control. In addition to this, sensory analysis revealed that the treatment P4M (1:3) was found as optimum ratio regarding taste, flavor, and aroma. Besides this, scanning electron microscopy (SEM) confirms that the high amount of EHPP resulted in the void holes while CY showed dense gel structure. The prepared yogurt with EHPP provides an excellent flavor, satisfying sweetness and homogeneous texture. These findings suggest the optimum formulation ratio of prepared yogurt was found to be P4M (1:3) for desirable attributes and consumer acceptance. The prepared yogurt from the EHPP presents the potential industrial applications.

Some of the most recent advances in enzymatic glycosylation processes focused on the production of important bioactive compounds have been analyzed. The applicability of different enzymes such as glycosidases, glycosyltransferases, glycophosphorylases and glycosynthases have been de-scribed around the review article considering their advantages and disadvantages of these biocat-alysts in the stereoselective and regioselective synthesis of different types of glycosylated mole-cules, phenolic and aliphatic alcohols, oligosaccharides, polysaccharides, glycoderivatives, glyco-peptides and glycoproteins with a clear focus on food and pharmaceutical chemistry. Therefore, these approaches combining the use of different catalytic systems, the improvement of tools such as immobilization technology, or chemical or genetic modification to improve the synthesization in the glycosylation process could be a very useful tool in a continuous biotechnological advance.

One of the most problematic forms of nature protection in Poland relates to landscape parks. On the one hand, they include the most valuable landscapes; on the other hand, the areas within the landscape park still have economic uses. Therefore, the monitoring of landscape changes within landscape parks is necessary in order to properly manage these forms of protection. The main objective of the study was to monitor the scale and nature of landscape transformations within the boundaries of landscape parks in Poland during the period 2000–2018 and to assess the possibility of using the landscape change index (LCI) to monitor the intensity of landscape transformations within this type of protected area. Filling a gap in the research on landscape changes, I developed and verified the possibility of using LCI for monitoring the intensity of landscape changes using the example of 12 landscape parks in the Lower Silesia region. Preliminary analyses of the transformations within all landscape parks in Poland showed an upward trend, both in terms of the number of types of identified landscape changes as well as their area. In spite of the large diversity and degree of transformation in landscape parks, several dominant processes can be observed. The largest number and area of changes during each of the analyzed periods were found in transformations within forest landscapes (temporary and permanent deforestation and forest maturation), which constitute the dominant type of land cover within most of the landscape parks. In open landscapes, changes mainly relate to afforestation and natural succession in meadows, pastures and arable land, as well as the transformation of arable land into mining areas. Twelve case studies, covering all landscape parks of the Lower Silesia, have shown that the LCI is an excellent tool for monitoring the intensity of landscape changes, but it is dependent on the accuracy of the source data. The analyses confirmed that, during the study periods, the changes in all 12 Lower Silesian landscape parks were at a low level, but their particular intensification took place in the years 2012–2018. The highest LCI was found in the area where a natural disaster had occurred (air tornado), which destroyed huge areas of forest in landscape parks. After changes in the forest landscape, the most frequently identified type of change in 2006–2012 is the transformation of non-forest landscapes into forest landscapes. The main reason for such changes was the expansion of forest into abandoned arable land, meadows and pastures. The use of the Corine Land Cover database to calculate LCI and monitor the intensity of landscape change revealed a low usability of the database for the year 2000 and a high usability for data from 2006–2018.

In the last two centuries, land use change (LUC) has been the most important direct changes driver for terrestrial ecosystems. To contrast the consequent ecosystems degradation, forward-looking spatial policies and target landscape and land-use planning processes, promoting a sustainable land use change, are needed. The present paper proposes a framework of action including different landscape planning and ecological approaches: from the spatial modelling to recognize the LUC and build different scenarios, to the ecosystem services (ESs) assessment to evaluate the possible environmental impacts. Three different scenarios were built: Trend, No-Tillage and Energy crops. The Sediment Delivery Ratio and Carbon Storage and Sequestration ESs were assessed and compared for each scenario. The aim of the paper is to support decision-makers and local communities into the landscape planning process. Results show that a regional development in line with past trend could lead to further land degradation. Instead, the two scenarios proposed in compliance with EU policies, could bring benefits only if related to moderate LUCs and respecting the naturally grass-vegetated land. From the local to global scale, a guided and shared LUC management allows implementing sustainable development, basing on a deep knowledge of physical-environmental but also social and economic issues.

Landscape restoration activities must be conducted through a transdisciplinary process, integrating social, economic, environmental, and governance aspects. Combining visions from the natural and social sciences is a challenge in highly complex territories, where unique ecosystem characteristics, economic processes, stakeholders of diverse nature, and different normativity converge. The harmonization of multiple techniques, such as multicriteria spatial analysis, expert knowledge elicitation, and social mapping, allows for an approach to defining landscape restoration areas in complex regions. This paper employs multiple techniques to define ecosystem restoration areas in a complex Colombian Andes landscape, integrating ecological and social components for sustainable development. We observed that areas of high and very high feasibility for ecological restoration, encompassing 179.5 hectares (4.84% of the study area), are predominantly located near primary forests. Although some areas have low feasibility for conservation processes, they should not be disregarded as they still require protection. Landowners prioritize watershed and soil restoration as the most important landscape restoration activity due to their interest in improving water-related ecosystem services. This proposal enables the identification of areas with higher restoration potential at the property level, facilitating prioritization and investment allocation for future implementation.

Lily tepals have a short lifespan. Once the tepals senesce, the ornamental value of the flower is lost. Some cultivars have attractive purple ovaries and fruits which greatly enhance the ornamental value of Asiatic hybrid lilies. However, little is known about the molecular mechanisms of anthocyanin biosynthesis in Asiatic hybrid lily ovaries. To investigate the transcriptional network that governs purple ovary coloration in Asiatic hybrid lilies, we obtained transcriptome data from green ovaries (S1) and purple ovaries (S2) of Asiatic ‘Tiny Padhye’. Comparative transcriptome analysis revealed 4228 differentially expressed genes. Differential expression analysis revealed that nine unigenes including four CHS genes, one CHI gene, one F3H gene, one F3′H gene, one DFR gene, and one UFGT gene were significantly up-regulated in purple ovaries. One MYB gene, LhMYB12-Lat, was identified as a key transcription factor determining the distribution of anthocyanins in Asiatic hybrid lily ovaries. Further qPCR results showed unigenes related to anthocyanin biosynthesis were highly expressed in purple ovaries of Asiatic ‘Tiny Padhye’ at stages 2 and 3, while they showed an extremely low level of expression in ovaries of Asiatic ‘Yellow Pixels’ during all developmental stages. In addition, shading treatment significantly decreased pigment accumulation by suppressing the expression of several unigenes related to anthocyanin biosynthesis in ovaries of Asiatic ‘Tiny Padhye’. These results could further our understanding of the molecular mechanisms of anthocyanin biosynthesis in Asiatic hybrid lily ovaries.

Intensive crop production and extensive use of harmful synthetic chemical pesticides create numerous socio-economic problems worldwide. Therefore, sustainable solutions are needed for insect pest control, such as biological control agents. The fungal insect pathogen Beauveria bassiana has shown considerable potential as a biological control agent against a broad range of insects. The insights into virulence mechanism of B. bassiana is essential to show the robustness of its use. B. bassiana has several determinants of virulence, including the production of cuticle-degrading enzymes (CDEs), such as proteases, chitinases, and lipases. CDEs are essential in the infection process as they hydrolyze the significant components of the insect's cuticle. Moreover, B. bassiana has evolved effective antioxidant mechanisms that include enzyme families that act as ROS scavengers, e.g., superoxide dismutases, catalases, peroxidases, and thioredoxins. In B. bassiana, the number of CDEs and antioxidant enzymes characterized in recent years. The enzymatic activities are crucial for the biological control potential and significantly advanced our understanding of the infection mechanism of B. bassiana. This review focuses on the progress detailed in the studies of these enzymes and provides an overview of enzymatic activities and their contributions to virulence.

Non-enzymatic glucose sensing is a crucial field of study because of the current market demand. This study proposes a novel design of glucose sensor with enhanced selectivity and sensitivity by using graphene Schottky diodes, which is composed of Graphene/Platinum Oxide/n-Silicon heterostructure. The sensor was tested with different glucose concentrations and interfering solutions to investigate its sensitivity and selectivity. Different structures of the device were studied by adjusting the platinum oxide film thickness to investigate its catalytic activity. It was found that the film thickness plays a significant role in the efficiency of glucose oxidation and hence in overall device sensitivity. Moreover, theoretical investigations were conducted using Density Function Theory (DFT) to better understand the detection method and the origins of selectivity. The working principle of the sensors puts it in a competitive position with other non-enzymatic glucose sensors. DFT calculations provided a qualitative explanation of the charges distributed across the graphene sheet within a system of a platinum substrate with D-glucose molecules above. The proposed graphene/PtO/n-Si heterostructure has proven to satisfy these factors, which opens the door for further developments of more reliable non-enzymatic glucometers for continuous glucose monitoring systems.

The development of a decision framework for landscape governance and management has become one of the prioritised policy instruments for actualising policy objectives relating to agri-food system, biodiversity conservation, nature restoration, environmental management, climate change mitigation and adaptation, net zero greenhouse gas emissions, and the transition to renewable energy supplies in the United Kingdom (UK). However, the landscape lens in policy-making is challenging because of the diverse landscape archetypes, environmental problems, and diverging policy targets that it must address. This highlights the importance of having a robust, evidence-based landscape decisions framework. To address this issue, this study undertakes a systematic review and transdisciplinary synthesis of research outputs from the Landscape Decisions Programme (LDP). This study compiles and synthesizes outputs from the LDP projects in the context of the relevant literature to develop an understanding of the relationships among the emerging evidence with respect to decision-making for more sustainable and multifunctional landscapes. The synthesis analyzed the drivers of landscape decisions, and methodological approaches used to generate evidence for decision-making. The emerging themes from the synthesis were distilled into five principles that can be used as a basis for a roadmap towards the development of a holistic landscape decisions framework.

Cancers arise from the accumulation of somatic genome mutations, with varying contributions of intrinsic (i.e. genetic predisposition) and extrinsic (i.e. environmental) factors. For the understanding of malignant clones, precise information about their genomic composition has to be correlated with morphological, clinical and individual features, in the context of the available medical knowledge. Rapid improvements in molecular profiling techniques, the accumulation of large amount of data in genomic alterations in human malignancies and the expansion of bioinformatic tools and methodologies have facilitated the understanding of the molecular changes during oncogenesis, and their correlation with clinico-pathological phenotypes. Far beyond a limited set of "driver" genes, oncogenomic profiling has identified a large variety of somatic mutations; and whole genome sequencing studies of healthy individuals have improved the knowledge of heritable genome variation. Nevertheless, main challenges arise from the skewed representation of individuals from varying population backgrounds in biomedical studies, and also through the limited extend in which some cancer entities are represented in the scientific literature. Content analyses of oncogenomic publications could provide guidance for the planning and support of future studies aiming at filling prominent knowledge gaps.

Cervi cornu has been extensively used in traditional medicine as an antioxidant and for the treatment of various disorders, including osteoporosis. However, since it is not easy to separate the active ingredient, absorption is not performed well. In this study, we extracted the low molecular weight (843Da) collagen NP-2007 from cervi cornu by enzyme hydrolyzation, and evaluated the therapeutic effect in a monosodium iodoacetate (MIA)-induced rat osteoarthritis model, and identified their molecular mechanisms. NP-2007 was orally administered at 50, 100, and 200 mg/kg for 21 d. Efficacy was evaluated based on serum parameters, inflammatory mediators, and mor-phological and histopathological analyses of knee joints. Production of matrix metalloproteinases, including MMP-2, MMP-3, and MMP-9, in the serum was higher in MIA-treated rats; however, these levels decreased after NP-2007 treatment. Serum levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and prostaglandin E2 were lower in the NP-2007 group than in the MIA group. Furthermore, the administration of NP-2007 resulted in effective preservation of both the synovial membrane and knee cartilage, and significantly decreased the transformation of fibrous tissue. This study indicates that NP-2007 can prevent and alleviate symptoms of osteoarthritis and have applications as a novel arthritis treatment.

In this paper, the effects of different food-grade enzymes on the antigenicity of casein (CN), β- lactoglobulin (β-LG) and ɑ-lactalbumin (ɑ-LA) in natural cow milk were studied. The degree of hydrolysis (DH), SDS-PAGE and molecular mas (MW) distribution of cow milk (CM) hydrolysates was assessed. Additionally, the residual antigenicity of CM hydrolysates was evaluated by using ELISA and western blotting with anti-CN, anti-β-LG and anti-ɑ-LA rabbit polyclonal antibody. The results showed that Alcalase and Protamex hydrolysis could efficiently reduce the antigenicity of CN, β-LG, ɑ-LA, showed a higher DH and the loss of density of CM proteins, as indicated by SDS-PAGE. The increasing of the low MW (<3 kDa) in CM hydrolysates was also presented. It was also found that Protamex, Alcalase could be more efficiently hydrolyzed major allergenic of CM than other enzymes for the development of hypoallergenic cow milk. Our research will lay a theoretical foundation for the study of hypoallergenic cow milk.

(R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol has been synthesised in 93% enantiomeric excess (ee) by asymmetric reduction of the corresponding ketone catalysed by a ketoreductase and NADPH as the co-factor in DMSO. (S)-N-(2,6-Dichloro-4-(1-hydroxyethyl)phenyl)acetamide has been synthesised in >98% ee by the same system. Both synthons are potential precursors for clenbuterol enantiomers. Clenbuterol is a β₂-agonist used in veterinary treatment of asthma in several countries. The drug is listed on the World Anti-doping Agency’s Prohibited list due to its effect on increased protein synthesis in the body. However, racemic clenbuterol has recently been shown to reduce the risk of Parkinson’s disease. In order to reveal which one (or both) of the enantiomers that cause this effect, the pure enantiomers need to be studied separately. Our biocatalytic approach in order to obtain enantiopure clenbuterol should be applicable to industrial scale.

Controlling surface-protein interaction during wastewater treatment is the key motivation for developing functionally modified membranes. A new biocatalytic thermo-responsive poly(vinylidene fluoride)(PVDF)/nylon-6,6/poly(N-isopropylacrylamide)(PNIPAAm) ultrafiltration membrane was fabricated to achieve dual functionality of protein-digestion and thermo-responsive self-cleaning. The PVDF/nylon-6,6/PNIPAAm composite membranes were constructed by integrating a hydrophobic PVDF cast layer and hydrophilic nylon-6,6/PNIPAAm nanofiber layer where trypsin enzymes were covalently immobilized. The immobilization density of enzymes on the membrane surface decreased with increasing PNIPAAm concentration, due to the decreased number of amine functional sites. Through a ultrafiltration study using a model solution containing BSA/NaCl/CaCl₂, the PNIPAAm containing biocatalytic membranes demonstrated a combined effect of enzymatic and thermo-switchable self-cleaning. The membrane without PNIPAAm revealed superior fouling resistance and self-cleaning with an R_PD of 22%, compared to membranes with 2 and 4 wt% PNIPAAm with 26% and 33% R_PD, respectively, after an intermediate temperature cleaning at 50°C, indicating that higher enzyme density offers more efficient self-cleaning than the combined effect of enzyme and PNIPAAm at low concentration. The conformational volume phase transition of PNIPAAm did not affect the stability of immobilized trypsin on membrane surface. Such novel surface engineering design offer a promising route to severe surface-protein contamination remediation in food and wastewater applications.

Plazomicin is a recently U.S. Food and Drug Administration (FDA)-approved semisynthetic aminoglycoside. Its structure consists of a sisomicin scaffold modified by adding a 2(S)-hydroxy aminobutyryl group at the N1 position and a hydroxyethyl substituent at the 6′ position. These substitutions produced a molecule refractory to most aminoglycoside-modifying enzymes. The main enzyme within this group that recognizes plazomicin as substrate is the aminoglycoside 2′-N-acetyltransferase type Ia [AAC(2′)-Ia], which reduces the antibiotic’s potency. Designing formulations that combine an antimicrobial with an inhibitor of resistance is a recognized strategy to extend the useful life of existing antibiotics. We have recently found that several metal ions inhibit acetylation of numerous aminoglycosides catalyzed by the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib]. In particular, Ag1+, which also enhances the effect of aminoglycosides by other mechanisms, is very effective in interfering with AAC(6′)-Ib-mediated resistance to amikacin. Here we report that silver acetate is a potent inhibitor of AAC(2′)-Ia-mediated acetylation of plazomicin in vitro, and it reduces resistance levels of Escherichia coli carrying aac(2′)-Ia. The resistance reversion assays produced equivalent results when the structural gene was expressed under the control of the natural or the blaTEM-1 promoters. The antibiotic effect of plazomicin in combination with silver was bactericidal, and the mix did not show significant toxicity to human embryonic kidney 293 (HEK293) cells.

In this study, we designed a new biosensing membrane for the development of an electrochemical glucose biosensor. To proceed, we used a chitosan-based hydrogel that entraps glucose oxidase enzyme (GOx) and we crosslinked the whole matrix using glutaraldehyde, which is known for its quick and reactive crosslinking behavior. Then, the stability of the designed biosensors was investigated over time according to different storage conditions (in PBS solution at temperatures of 4 °C and 37 °C and in the presence or absence of glucose). In some specific conditions, we found that our biosensor is capable to keep its stability for more than six months of storage. We also included catalase to protect the biosensing membranes from the enzymatic reaction by-products (e.g., hydrogen peroxide). This design protects the biocatalytic activity of GOx and enhances the biosensor lifetime.

Genome-scale metabolic models (GEMs) have been widely used for phenotypic prediction of microorganisms. However, the lack of other constraints in the stoichiometric model often leads to a large metabolic solution space inaccessible. Inspired by previous studies that take allocation of macromolecule resources into account, we developed a simplified Python-based workflow for constructing enzymatic constrained metabolic network model (ECMpy) and constructed an enzyme-constrained model for Escherichia coli (eciML1515) by directly adding a total enzyme amount constraint in the latest version of GEM for E. coli (iML1515), considering the protein subunit composition in the reaction, and automated calibration of enzyme kinetic parameters. Using eciML1515, we predicted the overflow metabolism of E. coli and revealed that redox balance was the key reason for the difference between E. coli and Saccharomyces cerevisiae in overflow metabolism. The growth rate predictions on 24 single-carbon sources were improved significantly when compared with other enzyme-constrained models of E. coli. Finally, we revealed the tradeoff between enzyme usage efficiency and biomass yield by exploring the metabolic behaviors under different substrate consumption rates. Enzyme-constrained models can improve simulation accuracy and thus can predict cellular phenotypes under various genetic perturbations more precisely, providing reliable guidance for metabolic engineering.

Of the manifold concepts in drug discovery and design, covalent drugs have re-emerged as one of the most promising over the past 20-or so years. All such drugs harness the ability of a covalent bond to drive an interaction between a target biomolecule, typically a protein, and a small molecule. Formation of a covalent bond necessarily prolongs target engagement, opening avenues to targeting shallower binding sites, protein complexes, and other difficult to drug manifolds, amongst other virtues. This opinion piece discusses frameworks around which to develop covalent drugs. Our argument, based on results from our research program on natural electrophile signaling, is that targeting specific residues innately involved in native signaling programs are ideally poised to be targeted by covalent drugs. We outline ways to identify electrophile-sensing residues, and discuss how studying ramifications of innate signaling by endogenous molecules can provide a means to predict drug mechanism and function and assess on- versus off-target behaviors.

Abstract: Changes in forest landscapes have been connected with human activity for centuries, which can be considered as one of the main driving forces of change in the global perspective. The spatial distribution of forests changes along with the geopolitical situation, demographic changes, intensification of agriculture, urbanization or changes in the land use policy. However, due to the limited availability of historical data, the driving forces of changes in forest landscapes are most often considered in relation to recent decades, without taking into account long-term analyzes. The aim of this paper is to determine the impact of natural and socio-economic factors on changes in forest landscapes within the protected area – Ślęża Landscape Park and its buffer zone in the aspect of long-term analyzes covering the period of 140 years (1883-2013). The comparison of historical and current maps, demographic data on 4 different periods as well as natural and location factors by using the ArcGIS software allowed analyzing selected driving forces of forest landscape transformations. We took into account natural factors like altitude, slope, exposure of the hillside and socio-economic drivers like population changes, distances to centers of municipalities, main roads and built-up areas.

Millions of people worldwide are affected by diabetes, a chronic disease that continuously grows due to abnormal glucose concentration levels present in the blood. Monitoring blood glucose concentrations is therefore an essential diabetes indicator to aid in the management of the disease. Enzymatic electrochemical glucose sensors presently account for the bulk of glucose sensors in the market. However, their disadvantages are that they are expensive and are dependent on environmental conditions, hence affecting their performance and sensitivity. To meet the increasing demand, non-enzymatic glucose sensors based on chemically modified electrodes for the direct electrocatalytic oxidation of glucose are a good alternative to the costly enzymatic-based sensors currently on the market, and the research thereof continues to grow. Nanotechnology-based biosensors have been explored for their electronic and mechanical properties, resulting in enhanced biological signalling through the direct oxidation of glucose. Copper oxide and copper sulfide exhibit attractive attributes for sensor application, due to their non-toxic nature, abundance, and their unique properties. Thus, in this review, copper oxide and copper sulfide-based materials, are evaluated based on their chemical structure, morphology, and fast electron mobility as suitable electrode materials for non-enzymatic glucose sensors. The review highlights the present challenges of non-enzymatic glucose sensors that have limited their deployment into the market.

Complex interactions between gene variants and environmental risk factors underlie the pathophysiological pathways in major psychiatric disorders. Autism Spectrum Disorder is a psychiatric condition in which susceptible alleles along with epigenetic memories contribute to the mutational landscape of the ailing brain. The present work reviews recent evolutionary, molecular, and epigenetic mechanisms potentially linked to the etiology of autism. First, we present a clinical vignette to describe clusters of maladaptive behaviors frequently diagnosed in autistic patients. Next, we microdissect brain regions pertinent to the nosology of autism as well as cell networks from the bilateral body plan. Lastly, we catalog a number of pathogenic environments associated with disease risk factors. This set of perspectives provides emerging insights into the dynamic interplay between epigenetic and environmental variation in the development of Autism Spectrum Disorders.

Abstract: The internationally accepted goals of eliminating climate gas emissions implies substantial investments in renewable energy (RE) facilities. This will inevitably lead to major impacts on landscapes. Landscape concerns linked to RE facilities are already leading to controversies in many local communities. In this article, we focus on the question of landscape democracy related to the establishment of RE facilities. Based on recommendations from the European Landscape Convention, an analytical framework is presented identifying three main dimensions of landscape democracy, followed by an overview of arrangements, procedures and methods that are or may be used to encourage democracy. The procedures and methods are analysed based on examples from Denmark and Norway. This is followed by an analysis of decision levels with a special focus on the principle of subsidiarity. Finally, recommendations are presented to strengthen landscape democracy in relation to the installation of RE-facilities.

Intratumor heterogeneity (ITH) is associated with therapeutic resistance and poor prognosis in cancer patients, and attributed to genetic, epigenetic, and microenvironmental factors. We developed a new computational platform, GATHER, for geostatistical modeling of single cell RNA-seq data to synthesize high-resolution and continuous gene expression landscapes of a given tumor sample. Such landscapes allow GATHER to map the enriched regions of pathways of interest in the tumor space and identify genes that have spatial differential expressions at locations representing specific phenotypic contexts using measures based on optimal transport. GATHER provides new applications of spatial entropy measures for quantification and objective characterization of ITH. It includes new tools for insightful visualization of spatial transcriptomic phenomena. We illustrate the capabilities of GATHER using real data from breast cancer tumor to study hallmarks of cancer in the phenotypic contexts defined by cancer associated fibroblasts.

A national green planning strategy has recently been introduced in the Italian urban planning sector, aimed at making all local initiatives undertaken nationwide consistent with each other. At a regional level, Friuli Venezia-Giulia has recently implemented a Landscaping Plan, which is of an urban planning and ecological nature at an intermediate level between national and local. This article describes the local green plan of Latisana, which has been entitled Ecopolitana, given that it is represents the experimental phase, at a regional level, of the possibilities offered by landscape planning and design. Specifically, it outlines the multi-disciplinary approach used, demonstrating how landscape planning can be compared to the sustainable development of cities, with specific regard to the agricultural sector. Regarding the agricultural sector, a low-intensity cropping model is also suggested, based on the principles of agroecology and landscape ecology, which has already been implemented in the historical rural landscape of Plasencis (UD) and developed through GIS analysis and remote sensing processes. Its aim is to be the starting point for the achievement of the goals set in the 2030 Agenda, and especially Goals 13 (Climate action) and 15 (Life on land), given the current scarcity of agroecological infrastructures in the area of Latisana (UD) and the high percentage of soil used for intensive cropping.

Rural landscapes are acknowledged for their potential to restore human health due to their natural characteristics. However, few studies have systematically analysed the impact of naturalness, landscape types, and combinations of landscape elements on restorativeness using both subjective and objective measurements. This study investigated the restorative effects of various rural landscapes in Guangzhou, employing electroencephalography and eye-tracking technologies to record physiological responses and using the Restorative Components Scale and the Perceived Restorativeness and Naturalness Scale to evaluate psychological responses. The results indicated the following: (1) There was a significant positive correlation between perceived naturalness and restorativeness, surpassing the impact of actual naturalness. (2) Different landscape types had a varying impact on mental health at the equal perceived naturalness. Natural forest landscapes and artificial forest landscapes exhibited the most substantial restorative effects among the natural and semi-natural landscapes examined, respectively, while settlement landscapes showed the highest restorative potential among the artificial landscapes. (3) Restorative properties varied across landscape elements, with identical elements yielding different benefits in different environments. Trees and water significantly enhanced restorativeness, whereas constructed elements such as roads and infrastructure reduced it. This study provides a scientific basis for restorative rural landscape design to enhance mental health and well-being.

Polyurethane (PU) is a polymer widely used by humans whose recycling is highly complex due his chemical structure, being limited to incineration or accumulation in landfills. Biodegradation by enzymes and microorganisms has been studied for decades as an effective method of biological decomposition. In this study, Tenebrio molitor larvae (T. molitor) were fed with polyurethane foams, which gut enzymes and microorganisms were capable of degrading the polymer by 35% in 17 days of treatment, producing a weight loss of 14% in the mealworm. Changes in T. molitor gut bacterial community and diversity were observed, which may be due to colonization of species associated with PU degradation. Physical and structural biodegradation in PU by T. molitor compared to virgin PU, was demonstrated by Fourier Transform InfraRed spectroscopy (FTIR), Thermal Gravimetric Analysis (TGA) and Scanning Electron Microphotography (SEM).

Crown of thorns starfish (Acanthaster planci) are coral predators with advantages of having toxicity in their venom and tissue regeneration capabilities. With all these characteristics, only a handful of studies have highlighted the association of microorganisms with this organism. Crown of thorns starfish are common in Fiji and their analyses of microbial diversity for secondary metabolites could be of great interest to the scientific community. This study is an attempt to investigate Fijian-based A. planci for their venom and associated actinomycetes antibacterial activity and further identify the type of enzymes present in the crude venom extract. The CoTS venom extract (0.192 g) harbor enzymes such as gelatinase, caesinase, and amylase. An abundant and potent actinomycete strain, represented as FJA1 showed antibacterial activity against Enterococcus faecium with an inhibition zone of 10 mm. Moreover, all pathogenic test microorganisms were resistant against concentrations of 500 µg and 1 mg of A. planci venom extract.

Cellulose is the most abundant polysaccharide in lignocellulosic biomass, where it is interlinked with lignin and hemicellulose. Bioethanol can be produced from biomass. Because breaking down biomass is difficult, cellulose-active enzymes secreted by filamentous fungi play an important role in degrading recalcitrant lignocellulosic biomass. We characterized a cellobiohydrolase (AfCel6A) and lytic polysaccharide monooxygenase LPMO (AfAA9_B) from A. fumigatus after they were expressed in Pichia pastoris and purified. The biochemical parameters suggested that the enzymes were stable; the optimal temperature was ~60 °C. Further characterization revealed high turnover numbers (kcat of 147.9 s-1 and 0.64 s-1, respectively). Surprisingly, when combined, AfCel6A and AfAA9_B did not act synergistically. Association of AfCel6A and AfAA9_B inhibits the activity of AfCel6A, an outcome that needs to be further investigated. However, addition of AfCel6A or AfAA9_B boosts the enzymatic saccharification activity of a cellulase cocktail and the activity of cellulase Af-EGL7. The supplementation of an enzymatic cocktail with AfCel6A or AfAA9_B boosted the yield of fermentable sugars from complex substrates, especially sugarcane exploded bagasse, by up to 95%. The synergism between the cellulase cocktail and AfAA9_B is enzyme- and substrate-specific, which suggests a specific enzymatic cocktail for each biomass.

Nowadays circular economy trend drives researchers in the recovery of various bioactive compounds from agri-food by-products. Enzyme-assisted extraction (EAE) is shown as an innovative green technology for the effective extraction of various phytochemicals from agri-food section by-products, therefore this study aimed to evaluate the application of EAE as green technology to obtain extracts from olive leaves (Olea europaea) for potential industrial production. EAE was conducted under various enzyme dose combinations, and incubation time (120 min). Obtained extracts were characterized in terms of total polyphenols (TP) and Total Antioxidant Activity (AA). Firstly, the enzyme synergistic effect in enzymatic extraction of polyphenols was evaluated. TP optimal extraction conditions (468.19 mg GAE/L) were achieved after EAE (50-50%) and for AA (69.85 AA%). According to the above results, a second experimental part occurred for the incubation time (min.) and enzyme dose (mL) of optimal extraction conditions of olive leaves. Results indicated EAE as an excellent choice for green extraction of polyphenols from the olive leaves.

Hazelnut, pistachio and cashew are tree nuts with health benefits but also with allergenic properties being prevalent food allergens in Europe. The allergic characteristics of these tree nuts after processing combining heat, pressure and enzymatic digestion were analyzed through in vitro (Western blot and ELISA) and in vivo test (Prick-Prick). In the analyzed population, the patients sensitized to Cor a 8 (nsLTP) were predominant over those sensitized against hazelnut seed storage proteins (Sprot, Cor a 9 and 14), which displayed higher IgE reactivity. The protease E5 effectively hydrolyzed proteins from hazelnut and pistachio, while E7 was efficient for cashew protein hydrolysis. When combined with pressured heating (autoclave and Controlled Instantaneous Depressurization (DIC)), these proteases notably reduced the allergenic reactivity. The combination of DIC treatment before enzymatic digestion resulted in the most effective methodology to drastically reduce or indeed eliminate the allergenic capacity of tree nuts.

NiFe alloy nanoparticles/graphene oxide hybrid (NiFe/GO) was prepared for electrochemical glucose sensing. The as-prepared NiFe/GO hybrid was characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD). The results indicated that NiFe alloy nanoparticles can be successfully deposited on GO. The electrochemical glucose sensing performance of the as-prepared NiFe/GO was studied by cyclic voltammetry and amperometric measurement. Results showed that NiFe/GO modified glassy carbon electrode had sensitivity of 173 μA mM⁻¹cm⁻² for glucose sensing with a linear range up to 5 mM, which was superior to commonly used Ni nanoparticles. Furthermore, high selectivity for glucose detection can be achieved by NiFe/GO. All the results demonstrated that NiFe/GO hybrid was promising for using in electrochemical glucose sensing.

The worldwide pandemic of coronavirus disease 2019 (COVID-19) has become an unprecedented challenge to global public health. With the intensification of the COVID-19 epidemic, the development of vaccines and therapeutic drugs against the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are also widespread. To prove the effectiveness and safety of these preventive vaccines and therapeutic drugs, available animal models that faithfully recapitulate clinical hallmarks of COVID-19 are urgently needed. Currently, animal models including mice, golden hamsters, ferrets, nonhuman primates and other susceptible animals have been involved in the study of COVID-19. 92 vaccine candidates have entered clinical trials after the primary evaluation in animal models, of which inactivated vaccines, subunit vaccines, virus-vectored vaccines and mRNA vaccines are promising vaccine candidates. In this review, we summarize the landscape of animal models and advanced vaccines with efficacy range from about 50% to more than 95%. In addition, we point out future directions for animal models and vaccine development, aiming at providing valuable information and accelerating the breakthroughs confronting SARS-CoV-2.

We explored the dynamics of the two interacting information systems. We show that for the Markovian marginal systems the driving force for information dynamics is determined by both the information landscape and information flux. While the information landscape can be used to construct the driving force to describe the equilibrium time reversible information system dynamics, the information flux can be used to describe the nonequilibrium time-irreversible behaviours of the information system dynamics. The information flux explicitly breaks the detailed balance and is a direct measure of the degree of the nonequilibriumness or time irreversibility. We further demonstrate that the mutual information rate between the two subsystems can be decomposed into the equilibrium time-reversible and nonequilibrium time-irreversible parts respectively. This decomposition of the mutual information rate (MIR) corresponds to the information landscape-flux decomposition explicitly when the two subsystems behave as Markov chains. Finally, we uncover the intimate relationship between the nonequilibrium thermodynamics in terms of the entropy production rates and the time-irreversible part of the mutual information rate. We found that this relationship and MIR decomposition still hold for the more general stationary and ergodic cases. We demonstrate the above features with two examples of the bivariate Markov chains.

This study reports the preparation of silica and nano-fructosome encapsulated Candida antarctica lipase B particles (CalB@NF@SiO2) and demonstration of their enzymatic hydrolysis and acylation. CalB@NF@SiO2 particles were prepared as a function of TEOS concentration (3-100 mM). Their mean particle size was 185 nm by TEM. Enzymatic hydrolysis was performed to compare catalytic efficiencies of CalB@NF and CalB@NF@SiO2. Catalytic constants (Km, Vmax, and Kcat) of CalB@NF and CalB@NF@SiO2 were calculated with Michaelis-Menten equation and Line-weaver Burk plot. Optimal stability of CalB@NF@SiO2 was found at pH 8 and temperature of 35 ℃. Moreover, CalB@NF@SiO2 particles were reused for seven cycles to evaluate their reusability. In addition, enzymatic synthesis of benzyl benzoate was demonstrated by an acylation reaction with benzoic anhydride. The efficiency of CalB@NF@SiO2 for converting benzoic anhydride to benzyl benzoate by the acylation reaction was 97%, indicating that benzoic anhydride was almost completely converted to benzyl benzoate. Consequently, CalB@NF@SiO2 particles are better than CalB@NF particles for enzymatic synthesis. In addition, they are reusable with high stability at optimal pH and temperature.

The worldwide competition to vaccinate against COVID-19 has highlighted the importance of immunization measures in containing the virus. Saudi Arabia, like the rest of the globe, must assess socio-demographic subtleties, chronic illnesses, vaccination effects, and public health policy implications as it navigates this complicated environment. This cross-sectional study examined Saudi COVID-19 vaccine in many ways. It examined the socio-demographic makeup of vaccine recipients, the prevalence of chronic conditions in this population, vaccine administration patterns, post-vaccination side effects, and vaccine-infection rates. A questionnaire-based online survey of 401 participants ensured gender, nationality, age, weight, and educational diversity. We analyzed vaccine manufacturer choice for each dosage, side effects after the first and second doses, and chronic diseases in the sample. Pfizer/BioNTech vaccines are preferred for all three doses, reflecting worldwide vaccination acceptance patterns. Side effects were not significantly different between vaccination kinds. Interestingly, immunization reduced infection rates, demonstrating the efficacy of COVID-19 vaccines. The data fills important information gaps and illuminates Saudi COVID-19 vaccination kinetics. These data support the global preference for mRNA vaccines, demonstrating the faith in this breakthrough technology. They also sponsor COVID-19 vaccine safety and effectiveness studies. The dramatic drop in infection rates among vaccinated people shows how vaccinations suppress the pandemic. These findings inform Saudi Arabia's immunization efforts. As booster doses become more common, long-term vaccination research is crucial. Vaccine reluctance, especially in certain demographics, must be addressed. Due to vaccines' protective potential, equitable vaccine distribution and large immunization programs are essential for herd immunity and pandemic management. This thorough cross-sectional study helps policymakers and healthcare practitioners build successful and inclusive COVID-19 immunization regimens in Saudi Arabia.

Smart electronic devices and telemedicine are widely used in humans' daily lives. This provides remote treatment of patients using information and communications technology. New telemedicine technologies, such as the Internet of Medical Things (IoMT), make it easier for medical and computing devices to communicate regularly and effectively. Critical motivations for adapting the IoMT are reduced cost, increased quality of life, and timely medical intervention. IoMT is significant because it enables continuous, real-time patient monitoring during routine everyday activities using a variety of wearables and sensors. With big data, the IoMT technology makes excellent use of Artificial Intelligence (AI) to support disease detection and health condition prediction, alerting patients and healthcare providers. Many research studies have been conducted to explore various aspects of IoMT and its applications in the real world. However, it is challenging to comprehend all the techniques and solutions proposed by the research community. Therefore, this survey sheds light on some crucial aspects of IoMT technologies and explores the potential research gaps and directions the research community could tackle. The survey examines and discusses the characteristics of IoMT standards, protocols, and types. It then delves into the layers of IoMT and distinguishes them into Fog and edge. The studies published under each type were explored, and the limitations of these works were highlighted. The research gaps and directions on IoMT approaches and technologies were also highlighted. With such findings and research directions, further research endeavors could be carried out to address the issues and existing limitations in the IoMT.

The integration of artificial intelligence (AI) technologies into business practices presents both opportunities and challenges for Sabah, Malaysia. This dynamic abstract explores the latest research problem at the intersection of AI and business in Sabah, focusing on optimizing resource allocation in agriculture and enhancing tourism experiences through AI-driven solutions.In Sabah's agricultural sector, AI holds immense potential to revolutionize traditional farming practices. With limited arable land and unpredictable weather patterns, farmers face significant challenges in maximizing crop yields while minimizing resource inputs. Through the application of machine learning, remote sensing, and IoT devices, researchers aim to develop precision farming techniques that can analyze soil health, monitor crop growth, and predict pest outbreaks with unprecedented accuracy. By optimizing resource allocation and enhancing decision-making processes, these AI-driven solutions have the potential to revolutionize Sabah's agriculture industry, promoting sustainability and resilience in the face of environmental uncertainties.Moreover, the tourism industry in Sabah stands to benefit from AI integration, particularly in enhancing visitor experiences and destination management. With its diverse natural landscapes and rich cultural heritage, Sabah attracts tourists from around the globe. AI-powered recommendation systems, tailored to individual preferences and behavior, have the potential to provide personalized travel itineraries, optimize resource allocation, and boost visitor satisfaction. Additionally, natural language processing (NLP) algorithms can analyze online reviews and social media sentiments, providing valuable insights for destination marketing and management strategies. By harnessing the power of AI, Sabah can elevate its tourism offerings, attract more visitors, and enhance its reputation as a premier travel destination.However, alongside these opportunities, challenges abound in the integration of AI into Sabah's business landscape. Concerns regarding data privacy, cybersecurity, and ethical implications must be carefully addressed to ensure the responsible and sustainable deployment of AI technologies. Furthermore, the digital divide and limited access to technology in rural areas pose barriers to widespread adoption, necessitating comprehensive strategies for capacity building and infrastructure development.In conclusion, the advancement of AI integration in Sabah's business landscape holds immense promise for driving innovation, economic growth, and sustainability. By addressing the research problems outlined in this abstract, researchers, policymakers, and industry stakeholders can collaboratively navigate the opportunities and challenges of AI integration, paving the way for a prosperous and inclusive future for Sabah, Malaysia.

In this inclusive review article, the focus is on navigating the dynamic landscape of literature education, particularly the profound pedagogical shifts observed in the aftermath of the pandemic. The article synthesizes global insights, delving into how educators have adapted to hybrid models and embraced digital tools, fundamentally transforming the reading, analysis, and engagement with literary works. Exploring the integration of digital tools in literature education, the review uncovers the transformative impact of technology on traditional pedagogies. It analyzes the challenges and opportunities inherent in adapting literature education to the digital era, emphasizing the need for inclusive practices and adaptability. The article concludes by suggesting future research directions, encompassing AI integration, inclusive practices, cultural variations, long-term effects of hybrid models, and effective pedagogical strategies for technology integration. With a comprehensive approach, this review not only summarizes the current state of literature education but also discusses its implications, offering a holistic understanding of the contemporary educational landscape and setting the stage for future research endeavors.

We performed a comprehensive analysis of angiosarcoma (AS) genomic biomarkers and their associations with the site of origin. We aimed to describe the genomic landscape of AS in a cohort of 143 cases of AS profiled by Caris Life Sciences. Data of Next Generation Sequencing (NGS) with a 592 gene panel was available for the entire cohort. Fifty-three cases had data of Whole Exome Sequencing (WES) which we used to study the microenvironment phenotype. Immuno-therapy (IO) response biomarkers: Tumor Mutation Burden (TMB), Microsatellite Instability (MSI) and PD-L1 status were included. IO-response markers were present in 36.4% of the cohort and in 65% of head and neck AS (H/N-AS) (p<0.0001). H/N-AS cases had predominantly muta-tions in TP53 (50.0%, p=0.0004), POT1 (40.5%, p<0.0001) and ARID1A (33.3%, p=0.5875). In breast AS, leading alterations were MYC amplification (63.3%, p<0.0001), HRAS (16.1%, p=0.0377), and PI3KCA (16.1%, p=0.2352). A microenvironment with a high immune signature, associated with better response to IO, was present in 13% of the cases. This signature was evenly distributed among different primary sites. We found that the molecular biology for AS varies significantly according to the primary site. Our findings can facilitate the design and optimiza-tion of therapeutic strategies for AS to overcome resistance to IO and targeted therapies.

Skeletal metastases of unknown primary (SMUP) represent a clinical challenge dealing with patients diagnosed with bone metastases. The management have improved significantly in the past years, however fraught with lack of evidences, approach to these patients held out hope for more systematic and tailored treatment—and some patients can achieve impressive gains. Nevertheless, in real-life practice the outlook at the beginning of the take in charge of SMUP is decidedly more somber. An incomplete translational relevance of pathological and clinical data on the mortality and morbidity rate has had unsatisfactory consequences for SMUP patients and their physicians. We examined several approaches to confront the available evidences and highlighted three key points that emerge. The characterization of the SMUP biologic profile is essential to drive clinical decisions, integrating genetic and molecular profile into a multi-step diagnostic work-up. Nonetheless, pragmatic investigation plan and therapy of SMUP cannot follow a single template; it must be adapted to different pathophysiological dynamics and coordinated with efforts of a systematic algorithm and high-quality data derived from statistically powered clinical trials within. This review argues that greater efforts are required to face the unmet need dealing with SMUP patients in oncology. Finally, we provide an original functional network analysis, identifying novel therapeutic targets.

Sulfite and kraft pulping are two principal methods of industrial delignification of wood. In recent decades, those have been considered as possibilities to pretreat recalcitrant wood lignocellulosics for enzymatic hydrolysis of polysaccharides and subsequent fermentation of obtained sugars to valuable bioproducts. Current work compares chemistry and technological features of two different cooking processes in the preparation of polysaccharide substrates for deep sacchari-fication with P. verruculosum glycosyl hydrolases. Bleached kraft and sulfite pulps were subjected to hydrolysis with enzyme mixture of high xylanase, cellobiohydrolase and β-glucosidase activities at a dosage of 10 FPU/g of dry pulp and fiber concentration of 2.5, 5 and 10%. HPLC was used to analyze soluble sugars after hydrolysis and additional acid inversion of oligomers to monosaccharides. Kraft pulp demonstrated higher pulp conversion after 48 h (74-99%), mostly resulted from deep xylan hydrolysis. Sulfite-pulp hydrolysates, obtained in similar conditions, due to higher hexose concentration (more than 50 g/L), had higher fermentability for industrial strains producing alcohols, microbial protein or organic acids. Along with saccharification, enzymatic modification of non-hydrolysed residues occurred, which led to decreased degree of polymerization and composition changes in two industrial pulps. As a result, crystallinity of kraft pulp increased by 1.3%, which opens possibilities for obtaining new types of cellulosic products in pulp and paper industry. The high adaptability and controllability of enzymatic and fermentation processes creates prospects for the modernization of existing factories.

Enzymatic hydrolysis of bovine and human hemoglobin yields a diversity of bioactive peptides, some of which are recognized for their antimicrobial properties. Certain small antimicrobial and anticancer peptides target protein synthesis inhibition. This study aims to produce bioactive peptides through enzymatic hemoglobin hydrolysis and evaluate their effects on cell growth inhibition, potentially serving as candidates for biological anticancer drugs. Rapid screening of candidate anticancer peptides derived from enzymatic hydrolysis of bovine and human hemoglobin was conducted using the Lepidium sativum radicle growth technique. The results demonstrate that: 1) the degree of hydrolysis (DH) significantly influences the production of bioactive peptides. DH levels of 3-10% yield considerably stronger radicle growth inhibition compared to DH 0 (native hemoglobin form), exhibiting three to four times greater intensity. 2) Certain peptide fractions from bovine hemoglobin exhibit higher activity than those from human hemoglobin. 3) The structural characteristics of peptides play a crucial role in the observed biological effects. 4) The α137-141 peptide is the most active among the fractions obtained from bovine (IC₅₀ = 29 ± 1 µg/mL) and human hemoglobin (IC₅₀ = 48 ± 2 µg/mL), standing out 10 to 15 times more potent than other hemoglobin fractions. In conclusion, these findings affirm the bioactivity of peptide fractions obtained from bovine and human hemoglobin. The study highlights how enzymatic hydrolysis of bovine and human hemoglobin can yield peptides that inhibit protein synthesis. Ultimately, these results suggest the feasibility of obtaining candidate peptides for biological anticancer drugs from both human and bovine hemoglobin sources. These scientific advances show new hope in the fight against cancer which affects a large number of people around the world.

The protein extract of Ulva australis hydrolyzed with alcalase and flavourzyme investigated multi-functional properties, including total antioxidant capacity (TAC), collagenase inhibitory and antibacterial activities. The #5 fraction (SP5) and #7 fraction (SP7) of U. australis hydrolysate from cation-exchange chromatography showed significantly high TAC, collagenase inhibitory and antibacterial effects against Propionibacterium acnes, and only Q3 fraction from anion-exchange chromatography showed high multi-functional activities. The eight peptides among 42 peptides identified by MALDI-TOF/MS and Q-TOF/MS/MS were selected from the results to screen molecular docking on target proteins, and were synthesized. Thr-Gly-Thr-Trp (TGTW) showed ABTS [2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging activity. Effect TAC as Trolox equivalence was dependent on the concentration of TGTW. The Asn-Arg-Asp-Tyr (NRDY) and Arg-Asp-Arg-Phe (RDRF) possessing collagenase inhibitory activity increased according to the increase of concentration and the IC50 values of them were 0.95 mM and 0.84 mM, respectively. Peptides, RDRF and His-Ala-Val-Tyr (HAVY) showed anti-P. acnes effects with IC50 values of 8.57 mM and 13.23 mM, respectively. These results suggest that the U. australis hydrolysate could be a resource for the application of effective nutraceuticals and cosmetics.

Ionic liquids have been recognised as interesting solvents applicable in the efficient lignocellulosic biomass valorisation, especially in the biomass fractionation into individual polymeric components or direct hydrolysis some of biomass fractions. Considering the chemical character of ionic liquids, two different approaches, paved the way for a fractionation of biomass. The first strategy integrated a pre-treatment, hydrolysis and conversion of biomass through the employment of hydrogen-bond acidic 1-ethyl-3-methyimidazolim hydrogen sulfate ionic liquid. The second one relied on the use of a three-step fractionation process with hydrogen-bond basic 1-ethyl-3-methylimidazolium acetate to produce high purity cellulose, hemicellulose and lignin fractions. The proposed approaches were scrutinised for wheat straw and eucalyptus residues. Those different biomasses allowed understanding that enzymatic hydrolysis yields are dependent on the crystallinity of pre-treated biomass. The use of acetate based ionic liquid allowed to change crystalline cellulose I to cellulose II and consequently enhanced glucan to glucose yield to 93.14.1 mol% and 82.91.2 mol% for wheat straw and eucalyptus, respectively. Whereas for hydrogen sulfate ionic liquid, the same enzymatic hydrolysis yields were 61.6  0.2 mol% for wheat straw and only 7.90.3 mol% for eucalyptus residues. These results demonstrate the importance of either ionic liquid character or biomass type on the efficient biomass processing.

The most relevant fungal disease of the olive tree in Portugal is anthracnose, which has negative effects on fruit destruction and consequently on the yield and quality of the olive oil. Moreover, the loss of quality caused by olive fruit fly is associated with the presence of fungi in the galleries made by the larvae. The present study focuses on the effect of olive anthracnose and olive fly on the content of bioactive compounds, namely on hydroxytyrosol (HYT) and its derivatives (health claim) in olive oils extracted from 'Galega Vulgar' and 'Cobrançosa' cultivars. The olives, with different damage levels (olive fly and anthracnose disease), were harvested in Castelo Branco (Center of Portugal) in organic rainfed orchards, at four harvest times during 2019, 2020 and 2021 harvest years. The fruits were immediately submitted to olive oil extraction. The results of the quality criteria show that Galega olive oils extracted from olives with a higher anthracnose incidence show no conformity for the Extra Virgin Olive Oil (EVOO) and Virgin Olive Oil (VOO) categories, with high acidity values and negative sensory notes accompanied by the disappearance of oleacein (the main phenolic compound of both monovarietal olive oils). Conversely, no sensory defects were observed in Cobrançosa olive oils extracted from fruit with high anthracnose and olive fly incidence. Moreover, despite a decrease in all the positive attributes associated with the cultivar, namely in oleacein and oleocanthal contents, quality criteria were still in accordance with the EVOO category. The total HYT and tyrosol (TYR) content (&gt; 5 mg/20g) allows the use of the health claim on the label of all the analysed Cobrançosa olive oils.

Shiga toxins (Stxs), and more specifically the Stx2a subtype, are the major virulence factors involved in enterohemorrhagic Escherichia coli (EHEC)-associated hemolytic uremic syndrome (eHUS); a life-threatening disease causing acute kidney injury, especially in children. Cleavage of Stxs A subunit, when followed by reduction, boosts the enzymatic activity causing damage to targeted cells. This cleavage was assumed to be mostly mediated by furin during Stx intracellular trafficking. Cleavage of A subunit, without reduction, changes the binding properties of Stxs for blood components during HUS pathogenesis. To investigate whether the cleavage could occur in the intestine, even prior entering target cells, Stx2a structure was characterized after its exposure to specific host factors present in human stool. The structure of Stx2a A subunit was determined by immunoblotting after electrophoretic separation under reducing conditions. Trypsin and chymotrypsin-like elastase 3B (CELA3B), two serine proteases, were identified as potential candidates that may trigger the extracellular cleavage of Stx2a A subunit directly after its secretion by EHEC in the gut. Whether this observation indeed translates to natural infections and plays a role in eHUS pathogenesis has yet to be determined as well as whether host's protease profile could affect disease development by changing the toxin’s biological features.

The enzymatic activities of bacterial isolates have been widely studied, but a spatial distribution of this activity is rarely focused. New antibiotic-producing microorganisms can be discovered in a more efficient manner if spatial statistical techniques are applied to the distribution of the activity of bacterial isolates in different terrains. This study is focused to generate a series of maps illustrating the spatial distribution of different soil parameters and the inhibition against relative-safe pathogens (like Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Salmonella, Pseudomonas fluorencens and Enterobacter cloacae) in an urban park in València (Spain). This spatial data has demonstrated a higher proportion of isolates was specifically allocated. This routine of data presentation is valuable for understanding bacterial population dynamics at a local level.

In this work, PMMA(Poly methyl methacrylate) microfluidic system was used as a micro-reactor for urea hydrolysis by urease enzyme with use conductivity principle and utilize sound level meter(SLM) App in smartphone as a novel detector by considering the peak height in the App as an indicate for urea concentration. the advantage of use small volume and how the reaction carried on in the microfluidic system with simple and low cost are discussed, and the results were analyzed and statically determine. The linearity, detection limit (3×noise )and Correlation Coefficient, 62.5-500 ppm, 31.25 ppm and 0.992 respectively also, recovery studied were between(98.5-100.13%).

Exposure to metals is known to generate oxidative stress in living organisms, which are able to respond with the induction of antioxidant defenses, both enzymatic and non-enzymatic. The aim of this work is to study the correlation among several non-enzymatic component of the antioxidant system, that are physiologically related to both metal sequestration and defense against metal-induced oxidative stress, using the blue mussels (Mytilus galloprovincialis) as model organism. Specimens of this marine bivalve were experimentally exposed to cadmium (Cd), used as oxidative stress risk inducer. Cd, metallothionein (MT), glutathione (GSH), malondialdehyde (MDA) contents, and glutathione reductase (GR) activity in gills and in digestive glands were assessed at 0, 12, 24, 48, 72 and 96 h. The obtained results provide new data about the relationships among the non-enzymatic antioxidant cellular components considered in this study. These constitute the prompt physiological responses to the risk of oxidative stress in blue mussels exposed to Cd in controlled laboratory conditions.

Given that 3-Phosphoinositide-dependent kinase 1 (PDK1) plays a crucial role in malignant biological behaviors of a wide-range of cancers, we further review the influence of PDK1 in breast cancer (BC). First, we describe the power of PDK1 in cellular behaviors and extensively demonstrate the interacting networks of PDK1 via PI3K-dependent/ PI3K-independent pathway. Then we enlighten the roles of PDK1 in carcinogenesis, growth and survival, metastasis, and chemoresistance in BC cells. More important, we sort the current preclinical or clinical trials of PDK1 targeted therapy in BC and find that even though at present no selective PDK1 inhibitor is available for BC therapy, but the combination trials of PDK1 targeted therapy and other agents have demonstrated some benefit. Thus, there is increasing anticipations that PDK1 targeted therapy will have its space in future therapeutic concepts of BC, and we hope to feature PDK1 in BC to the clinic and bring the new promising to patients for targeted therapies.

Pesticides are chemical products are used to protect crops to prevent or eliminate undesirable organisms. Pesticides can contaminate continental waters, air, soil and food products. The presence of pesticide residues must therefore be monitored in water and food using sensitive, reliable and broad-spectrum analytical methods, as there is a huge variety of pesticides. Biosensors are one of the screening methods with great potential for detecting residues below the maximum residue limits. The different sensing principles of enzymatic biosensors for pesticide analysis will be described. This review highlights the great potential of colorimetric, enzymatic biosensors for detecting pesticide residues in water and food. Moreover the development of dual colorimetric and fluorimetric sensors during the past years is presented. These methods are most often based on the enzyme acetylcholinesterase, whose activity is inhibited by pesticides. The different approaches used in the development of these biosensors will be detailed, based on different chemical substrates, fluorophores and nanomaterials. The advantages and disadvantages of each approach will be discussed. Finally, the development prospects for improving these biosensors will be presented.

This paper focuses on the relationship between Mental Health and the Landscape. It aims to find out how people respond to Biophilic inspired landscape design in a healthcare setting. The focal point is not to cure diseases but to help them deal with the physiological, psychological, and psycho-social imbalance and provide a healing environment for the overall well-being of an individual. For this study, a Multispecialty Hospital was selected where an Indoor Healing Garden is used as a retrofitting tool to reduce stress and thus reconnect humans with nature. A multi-method approach is being used for this study. Initially, a questionnaire was conducted for the targeted users categorized into three types – patients, staff, and visitors to know their longing for the landscape. Based on this data and available literature, an evidence-based design was proposed. This conceptual design model is then shown to the targeted user and the response is recorded. The data has then collaborated with similar studies done earlier and design elements are highlighted which helps in creating a restorative environment by reducing stress and increasing recovery rate and thus approaching sustainable development.

The value of landscape, as part of collective heritage, can be acquired by GIS due to the multilayer approach of the spatial configuration. Proficiency in geospatial technologies in order to collect, process, analyze, interpret, visualize and communicate geographic information is being increased by undergraduate and graduate students, but in particular by those who are training to become geography teachers at secondary education. This training can be carried out through personalized learning and distance learning methodology. Personalized GIS education aims to integrate students and enhance their understanding of landscape. Some teaching experiences are shown whereby opportunities offered by WebGIS will be described, through quantitative tools and techniques that will allow this modality of learning and improve its effectiveness. Results of this research show that students, through geospatial technologies, learn landscape as a diversity of elements but also the complexity of physical and human factors involved. Several conclusions will be highlighted: i) the contribution of geospatial training to education for sustainable development; ii) spatial analysis as a mean of skills acquisition about measures for landscape conservation; iii) expanding and applying acquired knowledge to other geographic spaces and different landscapes.

The analysis of the morphological features can be framed in different temporal and spatial scales, depending on the specific objectives and methodologies of the various scientific fields that find in them a valuable source of information. The inventory and assessment of the geomorphological heritage may be based not exclusively in geophysical factors, but also in its contribution to the structuring of the biosphere, in its interrelation with other types of heritage or even in its potential for research or education purposes. In this article, we proceeded to the selection of a set of geomorphosites, at different scales, in Serra do Alvão (northern Portugal), seeking to demonstrate the importance of the broad lines of relief and intermediate and detailed landforms to the organization of the cultural landscape. Based on a questionnaire applied to a sample of 104 persons, it was intended to assess the value of the geomorphosites, concerning the scientific, preservation, use, cultural and educational dimensions.

Oak woodlands are a keystone ecosystem that may not be sustainable under ongoing fire management regimes and climate change. For example, in 2014, sassafras saplings started to emerge in degraded woodlands at the 1200 ha Drury Conservation Area as part of research at the Bull Shoals Field Station in Taney County, Missouri where burning was initiated in 1999. After Spring (March) 2021 burnt, we examined trend in the potential community and ecosystem effects, we assessed sapling density, height, and specific leave weigh (SLW) of white oak and sassafras (<1.0 m) from fall 2021 through fall 2022. In fall 2021, sassafras density was 560/0.1ha with mean height of 25.42cm and SLW of 0.00436g/cm² while white Oak density was 171/0.1ha with mean height of 10.2cm and SLW of 0.00680g/cm. However, in fall 2022, Sassafras density was 582/0.1ha with mean height of 71.689cm and SLW of 0.00366 g/cm² meanwhile, white Oak density was 213/0.1ha with mean height of 50.544cm and SLW of 0.00563 g/cm². We analyzed mass loss for sassafras and white oak after buried for 198 days. The weight loss for sassafras was 0.857g while oak was 0.790g for 61 days of buried. Subsequent sassafras weight loss was 1.942g, 3.343g, 4.222g and 4.82g while that of white Oak was 1.877g, 2.862g, 3.344g and 4.28g for day 105, 153 and 198 respectively. The nutrients composition and carbon sequestration of sassafras and white oak species need to be determined to better understand the effect of their dominance in fire management regime of degraded oak woodland in Southwest Missouri Ozarks.

SOX proteins are transcription factors which play a role in regulating the development of pro-genitor cells and tissue differentiation. Twenty members are known, clustered in eight groups named A to H, and sharing a common DNA-binding domain called the HMG (high-mobility-group) box. Eleven of the SOX genes have been associated with genetic disorders so far, covering a broad spectrum of developmental diseases. SOX4 is a single-exon gene and belongs to the SOXC group together with SOX11 and SOX12. SOX4 variants were recently described to cause a highly penetrant but heterogeneous disorder, with a phenotypic spectrum ranging from mild developmental delay and learning difficulties to intellectual disability with congenital anomalies. Nineteen pathogenic variants were reported to date, generally de novo, heterozygous, and inactivating, either stop-gain or missense, the latter ones primarily targeting the HMG domain. Further, a bi-allelic variant was reported in a single consanguineous family. Copy number variants, leading to whole gene deletion or duplication, are rare and not clearly associated with a neurodevelopmental disorder. Many open questions remain, regarding the definition of variants of unknown significance, a possible role of missense variants outside the HMG domain, genotype-phenotype correlation, the range of phenotypic spectrum and modifying factors, and treatment options.

Over recent years, the importance of patent literature has become more recognized in the academic setting. In the context of artificial intelligence, deep learning, and data sciences, patents are relevant to not only industry but also academe and other communities. In this article, we focus on deep tomographic imaging and perform a preliminary landscape analysis of the related patent literature. Our search tool is PatSeer . Our patent bibliometric data is summarized in various figures and tables. In particular, we qualitatively analyze key deep tomographic patent literature.

Well differentiated liposarcoma (WD-LPS) is a relatively rare tumour, with less than 50 cases occurring per year in the UK. These tumours are both chemotherapy and radiotherapy resistant and present a significant treatment challenge requiring radical surgery. Little is known of the molecular landscape of these tumours and no current targets for molecular therapy exist. We aimed to carry out a comprehensive molecular characterisation of WD-LPS via whole genome sequencing, RNA-sequencing and methylation array analysis. A recurrent mutation within exon1 of FOXD4L3 was observed (chr9:70,918,189A>T; c.322A>T; p. Lys108Ter). Recurrent mutations were also observed in Wnt signalling, immunity, DNA repair and hypoxia-associated genes. Recurrent amplification of HGMA2 was observed, although this was in fact part of a general amplification of the region around this gene. Recurrent gene fusions in HGMA2, SDHA, TSPAN31 and MDM2 were also observed as well as consistent rearrangements between chromosome 6 and chromosome 12. Our study has demonstrated a recurrent mutation within FOXD4L3, which shows evidence of interaction with the PAX pathway to promote tumorigenesis.

The dysregulation of cellular metabolism is a hallmark of ageing. To understand the metabolic changes that occur as a consequence of the ageing process and to find biomarkers for age-related diseases, we conducted a metabolomic analysis of brain, heart, kidney, liver, lung and spleen in young (9-10 weeks) and old (96-104 weeks) wild type (mixed genetic background of 129/J and C57BL/6) mice using NMR spectroscopy. We found differences in metabolic fingerprints of all tissues and identified several metabolites to be altered in most tissues, suggesting that they may be universal biomarkers of ageing. In addition, we found distinct tissue-clustered sets of metabolites throughout the organism. The associated metabolic changes may reveal novel therapeutic targets for the treatment of ageing and age-related diseases. Moreover, the identified metabolite biomarkers could provide a sensitive molecular read-out to age determine the age of biologic tissues and to validate the effectiveness and potential off-target effects of senolytic drug candidates on both a systemic and tissue-specific level.

An evaluation of emerging issues in One Health (OH) in Sub-Saharan Africa was undertaken to map the existing OH initiatives in Sub-Saharan African (SSA) countries. Desk review, expert opinions survey, limited interviews and wider consultations with selected OH stakeholders were conducted. The strengths, weaknesses, opportunities and threats to OH initiatives were identified. OH influence, interest and impacts were evaluated. One Health is transiting from multidisciplinary to transdisciplinary concepts and OH viewpoint should move from ‘proxy for zoonoses’, to include issues of climate change, nutrition and food safety, social sciences, geography, policy and planning, economics, welfare and well-being, antimicrobial resistance (AMR), vector-borne diseases, toxicosis and pesticides issues. While the identified major strengths should be boosted, the weaknesses should be addressed.OH Networks in SSA were spatially and temporally spread across SSA and stakeholders were classified as key, latent, marginal and OH defenders. Imbalance in stakeholders’ representation led to hesitation in buying-in from stakeholders who are outside the main networks. Theory of change, monitoring and evaluation frameworks, and tools to standardized evaluation of OH policies is needed for sustained future of OH and the future OH engagement should be outputs and outcomes-driven and not activity-driven.National roadmap for OH implementation and institutionalization is necessary and proofs of concepts in OH should be verified and scaled-up. Dependence on external funding is unsustainable and must be addressed. Necessary policy and legal instrument to support OH nationally and sub-nationally should be implemented taking cognizance of contemporary issues like urbanization, endemic poverty and other emerging issues. Utilizing current technologies and OH approach to address ongoing pandemic of COVID-19 and other emerging diseases is desirable. Finally, OH implementation should be anticipatory and not reactive to significantly benefit budgeting and contain disease outbreaks in animal sources before the risk of spillover to human can be envisaged.

Currently, the use of numerical models for reproducing the landscape evolution of a river basin is part of the day-by-day research activities of fluvial engineers and geomorphologists. However, despite landscape modelling is based on a rather long tradition, and scientists and practitioners are trying to schematize the processes involved in the evolution of a landscape since decades, there is still the need for improving both the knowledge of the physical mechanisms and their numerical coding. The present review focuses on the first aspect, discussing the main components of a landscape evolution model and their more common schematizations, presenting possible open questions to be addressed towards an improvement of the reliability of such kind of models in describing the fluvial geomorphology.

The landscape image is the bridge of communication between people and forests, and the cut point of the supply-side reform of forest tourism products. The research collected 140 copies in total of forest landscape image drawings from non-art-major graduate students by randomly sampling during April and May, 2018, and constructed the landscape image conceptual model of forest by utilizing the landscape image sketching technique. The results showed that (1) In regard to linguistic knowledge, the natural landscape elements for instance, herbaceous plants, terrains, creatures, water and sky, and the broad-leaf forest objectively reflected not only the real forest landscape and the local native vegetation, but the variation of forest species with little attention. (2) On the perspective of spatial view, the sideways view indicated that graduate students preferred to watch forests at a moderate distance externally and few looked at forests internally. (3) In the view of self-orientation, the objective landscape indicated that graduate students preferred to demonstrate forest landscapes, they did not realize to interact with the environment. (4) On the aspect of social meaning, the scenic view and forest structure stated that graduate students preferred rural forest landscapes, not significantly for other special interests for forest. In conclusions, (1) the forest is thought to be a feature of people's life world and of rural scenes around homes, not an objective perception of the forest. (2) The forest is regarded as an important habitat for animals and a limited resource for people's life, production and recreation needs, into which people will go only to meet such needs. (3) The natural values of forests, like the ecology and aesthetics, etc. get more attention, while the social values of forests, like the life, production and culture receives rather low attention.

In order to reduce the waste of Akebia trifoliata peel and maximize its utilization. In this study, on the basis of single factor experiment and response surface method, the optimum technological conditions for the extraction of soluble dietary fiber from Akebia trifoliata peel by compound en-zyme method were obtained. The chemical composition, physical and chemical properties, structural characterization and biological activity of the purified soluble dietary fiber (AP-SDF) from the Akebia trifoliata peel were analyzed. We discovered that that the optimum yield was 20.87 % under the conditions of cellulase addition 600 U/g, enzymolysis time 100 min, solid-liquid ratio 1:24 g/mL and enzymolysis temperature 51 °C. At the same time, AP-SDF was a po-rous network structure cellulose type I acidic polysaccharose mainly composed of arabinoxylan (36.03%), galacturonic acid (27.40%) and glucose (19.00%), which possessed the structural charac-teristic peaks of the infrared spectra of polysaccharides, and the weight average molecular weight (Mw) was 95.52 kDa with good uniformity. In addition, AP-SDF exhibited high oil hold-ing capacity (15.11 g/g), good water holding capacity, swelling capacity, certain antioxidant ca-pacity in vitro, hypoglycemic activity in vitro of α-glucosidase inhibition and hypolipidemic ac-tivity in vitro of the binding ability of bile acids and cholesterol. These results will provide a theoretical basis for the development of functional products with antioxidant, hypoglycemic and hypolipidemic effects, it has certain application value in related industries.

Plants are exposed to a variety of abiotic and biotic stresses leading to increased formation of reactive oxygen species (ROS) in plant cells. ROS are capable of oxidizing proteins, pigments, lipids, nucleic acids, and other cell molecules, disrupting their functional activity. During the process of evolution, numerous antioxidant systems were formed in plants, including antioxidant enzymes and low-molecular-weight non-enzymatic antioxidants. Antioxidant systems perform neutralization of ROS and therefore prevent oxidative damage of cell components. In the present review, we focus on the biosynthesis of non-enzymatic antioxidants in higher plant cells such as ascorbic acid (vitamin C), glutathione, flavonoids, isoprenoids, including carotenoids, tocopherol (vitamin E), ubiquinone and plastoquinone. Their functioning and their reactivity with respect to individual ROS are described. The review is also devoted to the modern genetic engineering methods, which are widely used to change the quantitative and qualitative content of the non-enzymatic antioxidants in cultivated plants. These methods allow to obtain various plant lines with given properties in a rather short time. The most successful approaches for plant transgenesis and plant genome editing for the enhancement of the biosynthesis and the content of these antioxidants are discussed.

The integration of metal nanoparticles and solid carriers can achieve ideal stability, high load and good conductivity. In this work, copper nanoparticles (Cu NPs) were sequentially deposited on a cobalt metal-organic framework (Co-MOF) by bonding with exposed imino groups, followed by a reduction reaction to prepare a new Cu@Co-MOF composite. Cu@Co-MOF acts as a non-enzymatic electrochemical sensor to detect glucose (Glu) in an alkaline medium. The composite working electrode of Cu@Co-MOF/GCE (GCE = glassy carbon electrode) improves the electrocatalytic activity for Glu oxidation. Cu@Co-MOF/GCE shows excellent electrocatalytic performances in Glu concentration ranging 0.005~1.8 mmol∙L⁻¹ (mM): the sensitivities are 282.89 μA∙mM⁻¹∙cm⁻² in 0.005-0.4 mM Glu and 113.15 μA∙mM⁻¹∙cm⁻² in 0.4-1.8 mM Glu respectively with low detection limit of 1.6 μM (S/N = 3) and high selectivity and stability.

SRC homology 3 (SH3) domains are critical interaction modules that orchestrate the assembly of protein complexes involved in diverse biological processes. They facilitate transient protein-protein interactions by selectively interacting with proline-rich motifs (PRMs). A database search revealed 298 SH3 domains in 221 human proteins. Multiple sequence alignment of human SH3 domains is useful for phylogenetic analysis and determination of their selectivity towards PRM-containing peptides (PRPs). However, a more precise functional classification of SH3 domains is achieved by constructing a phylogenetic tree only from PRM-binding residues and using existing SH3-PRP structures and biochemical data to determine the specificity within each of the 10 families for particular PRPs. In addition, the C-terminal proline-rich domain of the RAS activator SOS1 covers 13 of the 14 recognized proline-rich consensus sequence motifs, encompassing differential PRP pattern selectivity among all SH3 families. To evaluate binding capabilities and affinities, we conducted fluorescence dot blot and polarization experiments using 25 representative SH3 domains and various PRPs derived from SOS1. Our analysis has identified 45 interacting pairs with binding affinities ranging from 0.2 to 125 micromolar out of 300 tested and potential new interactors of SOS1. Furthermore, it establishes a framework to bridge the gap between SH3 and PRP interactions and provides predictive insights into potential interactions of SH3 domains with PRMs based on sequence specifications. This novel framework has the potential to enhance the understanding of protein networks mediated by SH3-PRM interactions and be utilized as a general approach for other domain-peptide interactions.

Understanding influences of multiple stressors across the landscape on aquatic biota is important for conservation, as it allows for an understanding of spatial patterns and informs stakeholders of significant conservation value. Data exists for land use/landcover (LULC) and other physicochemical components of the landscape throughout the Appalachian region yet biological data is sparse. This dearth of biological data relative to LULC and physicochemical data creates difficulties in making informed management and conservation decisions across large landscapes. At the HUC12 watershed scale we sought to create a single score for both abiotic and biotic values throughout the central and southern Appalachian region. We used boosted regression trees (BRT) to model biological responses (fish and aquatic macroinvertebrate variables) to abiotic variables. Variance explained by BRT models ranged from 62-94%. We categorized both predictor and response variables into themes and targets respectively to better understand large scale patterns on the landscape that influence biological condition of streams. We combined predicted values for a suite of response variables from BRT models to create a single watershed score for aquatic macroinvertebrates and fish. Regional models were developed for fish but we were unable to develop regional models for aquatic macroinvertebrates due to the low number of sample sites. There was strong correlation between regional and global watershed scores for fish models but not between fish and aquatic macroinvertebrate models. Use of such multimetric scores can inform managers, NGOs, and private land owners regarding land use practices; thereby contributing to largescale landscape scale conservation efforts.

Reviewed are recent efforts leading to chemo-enzymatic syntheses of strongly fluorescent ribosides of nucleobase analogs, potentially applicable in analytical biochemistry and cell biology. Described are syntheses and properties of fluorescent purine, 8-azapurine and etheno-purine ribosides, obtained using various types of the purine nucleoside phosphorylase (PNP) as catalysts of ribosylation, and -ribose-1-phosphate (r1P) as a second substrate. In several instances, the ribosylation sites were different than the canonical purine N9. Some of the obtained ribosides show fluorescence yields close to 100%. Their main applications are assays of PNP, nucleoside hydrolases, and other enzyme activities both in vitro and, possibly, within the living cells, using fluorescence microscopy.

A novel interaction between the enzyme platelet-activating factor acetyl hydrolase (PAF-AH) and certain non-steroidal anti-inflammatory drugs (NSAIDs), such as sulindac, celecoxib, diclofenac and nimesulide, has been uncovered by this in-silico research. PAF-AH is known for its critical role in maintaining the fluidity and functionality of cell membranes by hydrolysing phospholipids and removing oxidized fatty acids. Since tumour microenvironments are largely marked by inflammation and oxidative stress, the discovery that these non-steroidal anti-inflammatory drugs can bind to the active pocket of PAF-AH. Suggests that they may be able to modulate its activity and thereby influence its role in cancer pathogenesis. Such modulation could lead to significant anti-tumour effects, including the reduction of inflammation, the inhibition of angiogenesis and the suppression of metastasis, particularly in cancers of the breast, colon, prostate, and lung. However, in certain con-texts, this interaction may cause the opposite effect, leading to cancer development. Therefore, this study is a gateway for the development of therapeutic strategies based on PAF-AH modulation and highlights the importance of the tumour microenvironment in the assessment of potential effects of NSAIDs. Furthermore, this finding may guide the selection of NSAIDs for the anti-inflammatory treatment of cancer patients, ruling out in-discriminate use of drugs that may promote neoplastic progression. This may also indicate the potential for repositioning specific NSAIDs within cancer treatment, thereby contributing to more precise and personalized therapeutic approaches.

Introduction: Mucopolysaccharidosis type I (MPSI) is an autosomal recessive lysosomal storage disorder characterized by deficient or absent α-L-iduronidase (IDUA) enzyme activity due to pathogenic variants in IDUA gene. Early treatment with hematopoietic stem cell transplantation and/or enzyme replacement therapy is associated with improved outcomes in this progressive multisystem disease. The diagnosis is usually delayed due to late presentation and nonspecific symptoms resulting in high morbidity and mortality. The incidence of MPSI in US is estimated to be 0.26:100,000, however, it is unknown in Kuwait. This pilot study was undertaken to screen MPSI in all Kuwaiti neonates born at Farwaniya Hospital over a period of 12-months. This study examined the incidence of MPSI in a major center in Kuwait for inclusion in the national newborn screening program to enable its early detection and adequate treatment. Methods: All Kuwaiti neonates born at Farwaniya Hospital, Kuwait from December 2021 to December 2022, were screened for MPSI. The screening consisted of determining IDUA enzyme activity in dried blood spots (DBS)-derived samples by Tandem Mass Spectrometry. A follow-up genetic analysis of IDUA gene is planned to screen the cases with diminished IDUA enzyme activity as second-tier testing. Results: A total of 618 newborns, including 331 (54%) males and 287 (46%) females, were screened. Twenty of them had deficient IDUA enzyme activity but showed negative genetic testing for IDUA. However, we have diagnosed one additional female baby with MPSI, who belonged to Farwaniya Hospital, but the parents chose to deliver in a private hospital. She presented at age three months with recurrent upper airway infections, snoring and extensive Mongolian spots. The molecular study revealed previously reported pathogenic nonsense variant in IDUA c.1882C>T; p.(Arg628Ter), associated with severe phenotype. That being included, MPSI is estimated to be about 0.3% among tested females and 0.2% of all screened cases in Kuwait. Conclusion: Our study is the first to evaluate the incidence of MPSI in Kuwait. Given the single center, small number of screened babies and the short study duration thus far, it is premature to calculate the incidence of MPSI. It is anticipated that as the study continues and more infants are examined, we would be able to estimate the incidence of this disease in our population correctly. Further studies including screening newborns in all maternity hospitals in Kuwait are needed to calculate the actual incidence of MPSI. Our data supports including MPSI in national newborn screening program to allow early initiation of treatment and thus improve disease outcome.

The construction of optimized biological fuel cells requires a cathode which combines the longevity of a microbial catalyst with the power density of an enzymatic catalyst. Laccase secreting fungi were grown directly on the cathode of a biological fuel cell to facilitate the exchange of inactive enzymes with active enzymes with the goal of extending the lifetime of laccase cathodes. Additionally, a functionally graded coating was developed to increase enzyme loading at the cathode. Directly incorporating the laccase producing fungus at the cathode extends the operational lifetime of laccase cathodes while eliminating the need for frequent replenishment of the electrolyte. Additionally, the hybrid microbial-enzymatic cathode addresses the issue of enzyme inactivation by using the natural ability of fungi to exchange inactive laccases at the cathode with active laccases. Finally, enzyme adsorption was increased through the use of a functionally graded coating containing an optimized ratio of titanium dioxide nanoparticles and single walled carbon nanotubes. The hybrid microbial-enzymatic fuel cell combines the higher power density of enzymatic fuel cells with the longevity of microbial fuel cells and demonstrates the feasibility of a self-regenerating fuel cell in which inactive laccases are continuously exchanged with active laccases.

Keywords: Parkinson’s disease; sleep disorders; GBA; Parkin