In a wide range of lymphoid neoplasms, the process of malignant transformation is associated to somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected genes commonly play important roles in cell cycle regulation, apoptosis-inducing signal transduction and DNA damage response, thus facilitating the emergence of malignant traits that impair immune surveillance and favor the emergence of different B-cell lymphoma subtypes. In the last two decades, the field has made a major effort to develop therapies that target these epigenetic alterations. In this review, we discuss which epigenetic alterations occur in non-Hodgkin B-cell lymphoma. Furthermore, we aim to present in close to comprehensive manner the current state-of-the-art in the preclinical and clinical development of epigenetic drugs. We focus on therapeutic strategies interfering with histone methylation and acetylation as these are most advanced in being deployed from the bench-to-bedside and have greatest potential to improve the prognosis of lymphoma patients.

: Cattle farming is an ancient practice, with roots in the early Neolithic era that has retained its status in the food industry today, with global beef market revenue amounting to $385.7B, as of 2018. Hence, cattle maintenance is naturally essential to cater to nutritional requirements of modern civilization. This extensive review aims to provide a holistic overview of cattle microbiome, analysing the native microbial composition within respiratory tract, gastrointestinal tract, reproductive tract, and skin. The dysbiosis associated with various diseases such as bovine respiratory disease, bovine digital dermatitis, mastitis, Johne's disease, uterine diseases (metritis and endometritis) and metabolic disorders (ruminal acidosis and ketosis) has been discussed. Moreover, various non-antibiotic microbial therapies including phage therapy, prebiotics and probiotics have been examined as potential means to reduce disease-associated dysbiosis. In general, this review highlights the importance of the microbiome in maintenance of health in cattle and its potential in alleviating bovine diseases, with an aim to enhance cattle health and production.

New notion of dimension as set, as two optimal numbers including metric number, dimension number and as optimal set are introduced in individual framework and in formation of family. Behaviors of twin and antipodal are explored in fuzzy(neutrosophic) graphs. Fuzzy(neutrosophic) graphs, under conditions, fixed-edges, fixed-vertex and strong fixed-vertex are studied. Some classes as path, cycle, complete, strong, t-partite, bipartite, star and wheel in the formation of individual case and in the case, they form a family are studied in the term of dimension. Fuzzification(neutrosofication) of twin vertices but using crisp concept of antipodal vertices are another approaches of this study. Thus defining two notions concerning vertices which one of them is fuzzy(neutrosophic) titled twin and another is crisp titled antipodal to study the behaviors of cycles which are partitioned into even and odd, are concluded. Classes of cycles according to antipodal vertices are divided into two classes as even and odd. Parity of the number of edges in cycle causes to have two subsections under the section is entitled to antipodal vertices. In this study, the term dimension is introduced on fuzzy(neutrosophic) graphs. The locations of objects by a set of some junctions which have distinct distance from any couple of objects out of the set, are determined. Thus it’s possible to have the locations of objects outside of this set by assigning partial number to any objects. The classes of these specific graphs are chosen to obtain some results based on dimension. The types of crisp notions and fuzzy(neutrosophic) notions are used to make sense about the material of this study and the outline of this study uses some new notions which are crisp and fuzzy(neutrosophic). Some questions and problems are posed concerning ways to do further studies on this topic. Basic familiarities with fuzzy(neutrosophic) graph theory and graph theory are proposed for this article.

Factorization reduces computational complexity and is therefore an important tool in statistical machine learning of high dimensional systems. Conventional molecular modeling, including molecular dynamics and Monte Carlo simulations of molecular systems, is a large research field based on approximate factorization of molecular interactions. Recently, the local distribution theory was proposed to factorize global joint distribution of a given molecular system into trainable local distributions. Belief propagation algorithms are a family of exact factorization algorithms for trees and are extended to approximate loopy belief propagation algorithms for graphs with loops. Despite the fact that factorization of probability distribution is their common foundation, computational research in molecular systems and machine learning studies utilizing belief propagation algorithms have been carried out independently with respective track of algorithm development. The connection and differences among these factorization algorithms are briefly presented in this perspective, with the hope to intrigue further development in factorization algorithms for physical modeling of complex molecular systems.

The Indus basin is considered as the one with the highest dependence on snowmelt runoff in High Mountain Asia. The recent High Mountain Asia snow reanalysis enables to go beyond previous studies by evaluating both snowmelt and snow sublimation at the basin scale. Over 2000-2016, basin-average snowmelt is 101 11 Gt.a^-1 (121 ± 13 mm.a^-1), which represents about 25-30% of basin-average annual precipitation. Snow sublimation accounts for 11% of the mean annual snow ablation, but with a large spatial variability across the basin.

Commonly macrophages are categorized into M1 and M2 subsets. M1 macrophages are defined as inflammatory cells and may contribute to tissue injury, while, M2 macrophages play a central role in tissue remodeling and control of immune responses. It seems that the existence of these cells in graft location is effective for control of inflammation and improvement of transplantation consequences. Although the relative contribution of M2 cells in organ transplantation is not clear, the accumulation of these cells in acute and chronic injury models of transplantation was shown. In some cases, the depletion of M2 cells leads to the amelioration of disease; however in other causes, skewing the response in M2 cells leads to an augmentation of graft fibrosis and worsening of graft condition. In spite of these findings, the benefits of such strategies and their implications in human disease are not clearly understood. The purpose of this mini-review is to highlight the role of alternatively activated M2-type macrophages in the improvement or reduction of the kidney transplantation outcome.

Natural carotenoids are secondary metabolites that exhibit antioxidant, anti-inflammatory and anti-cancer properties. These types of compounds are in high demand by pharmaceutical, cosmetic, textile and food industries, leading to the search for new natural sources of carotenoids. In recent years, the production of carotenoids from bacteria has become of great interest for industrial applications. In addition to carotenoids with C40-skeletons, some bacteria have the ability to synthesize characteristic carotenoids with C30-skeletons. In this regard, a great variety of methodologies for the extraction and identification of bacterial carotenoids has been reported and this is the first review that condenses much of this information. To understand the diversity of these carotenoids, we present their biosynthetic origin in order to focus on the methodologies employed in their extraction and characterization. Special emphasis has been made on high-performance liquid chromatography-mass spectrometry (HPLC-MS) for the analysis and identification of bacterial carotenoids. We end up this review showing their potential commercial use of bacterial carotenoids. This review is proposed as a guide for the identification of these metabolites, which are frequently reported in new bacteria strains.

Microscale surgery on single cells and small organisms have enabled major advances in fundamental biology and in engineering biological systems. Examples of applications range from wound healing and regeneration studies to the generation of hybridoma to produce monoclonal antibodies. Even today, these surgical operations are often performed manually, but they are labor-intensive and lack reproducibility. Microfluidics has emerged as a powerful technology to control and manipulate cells and multicellular systems at the micro- and nanoscale with high precision. Here, we review the physical and chemical mechanisms of microscale surgery, and the corresponding design principles, applications, and implementations in microfluidic systems. We consider four types of surgical operations: 1) Sectioning, which splits a biological entity into multiple parts, 2) ablation, which destroys part of an entity, 3) biopsy, which extracts materials from within a living cell, and 4) fusion, which joins multiple entities into one. For each type of surgery, we summarize the motivating applications and the microfluidic devices developed. Throughout the review, we highlight existing challenges and opportunities. We hope that this review will inspire scientists and engineers to continue to explore and improve microfluidic surgical methods.

The main purpose of this paper is to present a comprehensive view of the application mathematical models in the designing and implementing SSCM beside to solving problems and making decision. The research questions are: what mathematical models are used for designing and implementing sustainable supply chain management, how to use them, which industries implemented in, what modules of SSCM depth in and finally finding the gaps of researches. The methodology of research is Systematic Literature review through peer review papers which are published in high ranking journals. In this paper, First, we search all papers through scientific data bases like Scopus, science direct, MDPI, Springer, Google Scholar, then, screening papers based on the criteria such as subject of paper, journals impact factor which is published in-should be peer review journal- and relative content of the papers. Finally, we selected 245 papers with three steps screening through 2806 papers that they have enough quality and relative to our research goals for context analysis. Through context analysis, first we categorized the information of the papers and drew the current situation of researches in the framework of our topic. Then, we evaluate and compare the goals of sustainability and current situation and found the gapes, then, offered new suggestions like implementing SSCMs models in pollutant industries like casting industry, Heavy industry, coal Industry and so on. On the other hand, there are gaps in researches in some modules of SSCM such as packaging, designing products, etc.

With the advent of microservice-based software architectures, an increasing number of modern cloud environments and enterprises use operating system level virtualization, often referred to as containers. Docker Swarm is one of the most popular container orchestration infrastructures, providing high availability and fault tolerance. Occasionally discovered container escape vulnerabilities allow adversaries to execute code on the host operating system and operate within the cloud infrastructure. We show that docker swarm is currently not secured against misbehaving manager nodes and allows a high impact, high probability privilege escalation attack that we refer to as leadership hijacking. Cloud lateral movement and defense evasion payloads allow an adversary to leverage the docker swarm functionality to control each and every host in the underlying cluster. We demonstrate an end-to-end attack, in which an adversary with access to an application running on the cluster achieves full control of the cluster. To reduce the probability of a successful high impact attack, container orchestration infrastructures must reduce the trust level of participating nodes and in particular, incorporate adversary immune leader election algorithms.

The latest EU regulation on geographical indications (EU Regulation No. 1151/2012) has intro-duced a set of new tools for the protection and enhancement of food products in rural areas, under the group name of optional quality term (OQT). The Commission Delegated EU Regulation, No. 665/2014, regulated the conditions for the use of the optional quality term «mountain product» (MP), to support the implementation of a mountain value chain. This new tool is aimed at pro-moting local development, maintaining the economic activities in mountain areas and redistrib-uting wealth, whilst, at the same time, promoting the territory. Pecorino and goat cheeses are typ-ical Italian cheeses made usually with whole raw ewe's or raw goat's milk, without starter cul-ture addition. In an attempt to characterize these productions, the aim of this study was to inves-tigate the evolution of enterococci during the production and ripening of Pecorino cheese made in three different farms, located in Umbria, Italy in areas facing natural or other specific constraints as stipulated by Regulation 1305/2013 on support for rural development by the European Agri-cultural Fund for Rural Development (EAFRD). Enterococci are enteric organisms which are commonly isolated from ewe and goat's milk production in Umbria, Italy. Counts of enterococci in raw milk ranged from 1.75 for ovine milk to 3.62 for ewe milk and a marked reduction was observed after thermization especially in ovine milk. Out of 100 isolates, 69 were E. faecium, 23 E. durans, 8 E. faecalis and 2 E. casseliflavus and the distribution of species between farms and be-tween samples showed a prevalence of E. faecium in ovine farms and E. durans in ewes farms, with an equal distribution between samples. High percentages of susceptible isolates were found for amoxicillin/clavulanic acid, ampicillin, chloramphenicol, sulphamethoxazole, sulphameth-oxazole/trimethoprim, ticarcillin, vancomycin. A high prevalence of resistant strains (> 30%) was observed for amikacin, ciprofloxacin, ceftriaxone, kanamycin, tetracycline. A comparison of this results with those of previous works on similar dairy products revealed high levels of resistance to antimicrobials which needs to be addressed.

Climate adaptation is a major challenge. Chasing the sufficient amount of hay is getting in higher priority. Distant mass hay producers give favourable offers despite long distances. Quality is also gaining position and indicators like RFQ (Relative Forage Quality) is highlighting the marketing language. Hay market as we knew no longer exists in Hungary. Most farmers produce their own hay and do not spend extra cents to buy bales. Climate change however, force them to adapt and store more bales for the future. Horse owners and dairy farmers are the main driver to convince hay producers to provide high quality forage. We gathered Hungarian regional hay-price information and evaluated the trends in this sector. The demand-driven hay-price is in contradiction with premium quality timothy grass hay.

Recent evidence has highlighted the critical role of memory cells in maintaining lifelong food allergies, thereby identifying these cells as therapeutic targets. IgG⁺ memory B cells replenish pools of IgE-secreting cells upon allergen exposure, which contract thereafter due to the short lifespan of tightly regulated IgE-expressing cells. Advances in the detection and highly dimensional analysis of allergen-specific B and T cells from allergic patients have provided insight on their phenotype and function. The newly identified Th2A and Tfh13 populations represent a leap in our understanding of allergen-specific T cell phenotypes, though how these populations contribute to IgE memory responses remains poorly understood. Within, we discuss the mechanisms by which memory B and T cells are activated, integrating knowledge from human systems and fundamental research. We then focus on memory reactivation; specifically, on the pathways of secondary IgE responses. Throughout, we identify areas of future research which will help identify immunotargets for a transformative therapy for food allergy.

Omics technologies, viz., genomics, transcriptomics, proteomics, metabolomics, and phenomics, are becoming an integral part of virtually every commercial cereal breeding program because they provide substantial dividends per unit time in both pre-breeding and breeding phases. Continuous advances in cereal-omics promise—in combination with time efficiency—the cost benefits. In this review, we provide a comprehensive overview of the established cereal-omics methods in five major cereals, viz., rice, sorghum, maize, barley, and bread wheat. We cover the evolution of technologies in each omics section independently and concentrate on their use to improve economically important agronomic as well as biotic and abiotic stress-related traits. Advancements in the (1) identification, mapping, and sequencing of molecular/structural variants, (2) high-density transcriptomics data to study gene expression patterns, (3) global and targeted proteome profiling to study protein structure and interaction, (4) metabolomic profiling to quantify organ level small-density metabolites and their composition, and (5) high-resolution high-throughput image-based phenomics approaches are surveyed in this review.

Background An outbreak of African swine fever (ASF) in China in 2020 has led to an unprecedented shortage of fraxiparin. Most patients, especially those kept in hospital for surgery, are currently treated with prophylactic anticoagulation (AC). In search of alternatives for fraxiparin, we found no sufficient data on alternatives for neurosurgical patients, such as tinzaparin of European origin. We compared fraxiparin and tinzaparin concerning adverse events (bleeding versus thromboembolic events) in neurosurgical patients. Methods Between 2012 and 2018, 517 neurosurgical patients with benign and malignant brain tumors as well as 297 patients with subarachnoid hemorrhage (SAH) were treated in the Department of Neurosurgery, University Hospital Leipzig receiving prophylactic anticoagulation within 48 hours. In 2015, prophylactic anticoagulation was switched from fraxiparin to tinzaparin throughout the university hospital. In a retrospective manner, the frequency and occurrence of adverse events (rebleeding and thromboembolic events) in connection with the substance used was analyzed. Statistical analysis was performed using Fisher’s exact test and the chi-squared test. Results Rebleeding rates were similar in both fraxiparin and tinzaparin cohorts in patients being treated for meningioma, glioma, and SAH combined (8.8 vs 10.3%). Accordingly, the rates of overall thromboembolic events were not significantly different (5.5% vs 4.3%). The severity of rebleeding did not vary. There was no significant difference among subgroups when compared for deep vein thrombosis (DVT) or pulmonary embolism (PE). Conclusion In this retrospective study, tinzaparin seems to be a safe alternative to fraxiparin for AC in patients undergoing brain tumor surgery or suffering from SAH.

The mammalian gut ecosystem plays critical roles in multiple functions related to health and homeostasis. In many cases, disturbances in the gut ecosystem are associated with a large number of metabolic and chronic diseases and disorders such as diabetes, cancer, and obesity. A diverse community of microorganisms ranging from viruses to bacteria comprise the gut microbiota, which is often considered as an organ in itself. Recent studies have profiled the influence of lifestyles and dietary behavior by comparing the gut microbiome of populations with different cultural underpinnings. In this review, we provide an overview of the studies which report the influence on the gut microbial composition of dietary and lifestyle patterns in different contexts such as western industrialized countries and indigenous cultures (corresponding to different lifestyle gradients such as hunter-gatherers and pastoralists) and how this association may influence health and disease.

Safety and quality are key issues for the food industry. Consequently, there is a growing demand to preserve the food chain and products against substances toxic, harmful to human health such as contaminants, allergens, toxins, or pathogens. For this reason, it is mandatory to develop highly sensitive, reliable, rapid, and cost-effective sensing systems/devices such as electrochemical sensors/biosensors. Generally, conventional techniques are limited by long time of analyses, expensive and complex procedures, and they require skilled personnel. Therefore, the development of performant electrochemical biosensors can significantly support the screening of food chain and products. Here, we report some of the recent developments in this area and analyze the contributions produced by electrochemical biosensors in the food screening and the challenges to address.

The rise in the volume, variety and complexity of data in healthcare has made it as a fertile-bed for Artificial intelligence (AI) and Machine Learning (ML). Several types of AI are already being employed by healthcare providers and life sciences companies. The review summarises a classical machine learning cycle, different machine learning algorithms; different data analytical approaches and successful implementation in haematology. Although there are many instances where AI has been found to be great tool that can augment the clinician’s ability to provide better health outcomes, implementation factors need to be put in place to ascertain large-scale acceptance and popularity.

Muscle is one of the most critical organs for mammals, which governs multiple movement and physiological functions. Circular RNA (circRNA) is a kind of novel endogenous RNA without 5'-Caps and 3'-poly(A) structures formed by pre-mRNA's back-splicing. RNA binding proteins (RBPs) control the production and degradation of circRNA, help nucleus-cytoplasm transport and locate circRNA, and regulate circRNA translation. Therefore, circRNAs and the chaperoned RBPs play critical roles in muscle growth, development, and disease progression. In this review, we systematically characterize the possible molecular mechanism of circRNA-protein interactions. Also, we summarize the latest researches on circRNA-protein interactions in muscle development and diseases. Besides, we provide several valid prediction methods and experimental verification approaches. Our review reveals the importance of circRNAs and their protein chaperones and provides a reference for further study in this field.

The purpose of this paper is to study the sliding mode control as a Ricci flow process in the context of a three-story building structure subjected to seismic waves. The stability conditions result from two Lyapunov- functions, the first associated with slipping in a finite period of time, and the second with convergence of trajectories to the desired state. Simulation results show that the Ricci flow control leads to the minimization of the displacements of the floors. 3D Ricci solitons projection via a semi-conformal mapping to a surface is also studied.

The Newton-Hooke duality and its generalization to arbitrary power laws in classical, semiclassical and quantum mechanics are discussed. We pursue a view that the power-law duality is a symmetry of the action under a set of duality operations. The power dual symmetry is defined by invariance and reciprocity of the action in the form of Hamilton’s characteristic function. We find that the power-law duality is basically a classical notion and breaks down at the level of angular quantization. We propose an ad hoc procedure to preserve the dual symmetry in quantum mechanics. The energy-coupling exchange maps required as part of the duality operations that take one system to another lead to an energy formula that relates the new energy to the old energy. The transformation property of Green function satisfying the radial Schrödinger equation yields a formula that relates the new Green function to the old one. The energy spectrum of the linear motion in a fractional power potential is semiclassically evaluated. We find a way to show the Coulomb-Hooke duality in the supersymmetric semiclassical action. We also study the confinement potential problem with the help of the dual structure of a two-term power potential.

In view of the preparation for a post-LHC collider, the high-energy physics (HEP) community started from 2010 to discuss various options, including the use of HTS for very high field dipoles. Therefore, a small program was set in Europe aiming at exploring the possibility of using HTS for accelerator quality magnets. Based on various EU funded programs, though at modest levels, has enabled the European community of accelerator magnets to start getting experience in HTS and addressing a few issues. The program was based on use of REBCO tapes to form 10 kA Roebel cables, to be used to wind small dipoles of 30-40 mm aperture in the 5 T range. The dipoles are designed to be later inserted in a background dipole field (in Nb3Sn), to reach eventually a field level in the 16-20 T range, beyond the reach of LTS. The program is currently underway: more than 1 km tape of high performance (Je > 500 A/mm2 at 20 T, 4.2 K has been manufactured and characterized, various 30 m long Roebel cables have been assembled and validated up to 13 kA, a few dipoles have been wound and tested, reaching at present 4.5 T in stand-alone (while a dipole made from race track coils with no-bore exceeded 5 T using stacked tape cable) and a test in a background field is being organized.

Together with display and input, storage and processing are requisite to computing. While storage technologies have improved tremendously in capacity and speed over the years, the basic principles enabling information storage into digital 1 and 0 remains the same: induction of phase change in the storage substrate. But recently, there has been much research into structural phase change material (SPCM) and exploration of its possible use in various types of memory storage applications. Despite unconventional use of structural change between amorphous and crystalline state as well as that between crystal structures for encoding information, key barriers for its widespread use remains access speed, capacity to cost ratio, and fidelity of storage. Hence, given the performance requirement of SPCM for memory applications, what are the material and design considerations that feed into translating a promising application into a practical reality? Given the important role of kinetic and thermal energy in structural organization of a phase change material, precise characterization of structural change in the material with external physical factors such as heat, voltage and current, is critical for storage material design. Next comes the precision at which individual memory cells for storing single bits of information could be defined reproducibly and at high fidelity using SPCM. In congruent with memory cell definition lies the equally important aspect of constraining the field characteristics used in modulating the phase state of the memory medium. Specifically, while heat is useful for mediating the “melting” of a crystalline material into its amorphous state, heat conduction is less useful for transferring the “switch command” from the effector to the memory material. More importantly, choice of structural phase change material for memory applications likely revolves around those where individual memory cells could be defined in a cross array format, which is amenable to high density information storage. Durability and fidelity of information storage are additional factors of design that favours selection of SPCM with phase change occurring at narrow operating windows without hysteresis over extended cycling. But, the most important requirement is speed of access. To this end, energetic cost of phase transitions might affect operation of the phase change memory at the system level: for example, usage of large current for high energy transition step may impact on device durability. Ultimately, there is a fundamental limit on the number of reproducible phase transitions in a SPCM before fidelity of information storage is no longer guaranteed. Hence, what are the drivers for uptake of phase change memories in consumer devices? Performance gains must be realized in access speed, storage capacity, form factor, and fidelity of information storage for practical application of structural phase change memories.

Pakistan is an important country located in South Asia and ranks the world's sixth most populous country. It has diverse landscapes with their own specific vegetation. The country specific vegetative diversity has a great ecological and economic impact on the conservation of local fauna. It has huge potential for sustainable beekeeping industry if properly exploited. Beekeeping in Pakistan is mainly focused in Khyber Pakhtunkhwa and central and north regions of Punjab provinces but nowadays it is growing rapidly across the country. Honey produced in Pakistan enjoys good repute in the Middle East due to its unique taste and quality. Pakistan exports around 4000 tons of the honey with the worth of about $ 23.00 million to Arab countries every year.

Low-loss photonic waveguides in lithium niobate offer versatile functionality as nonlinear frequency converters, switches, and modulators for integrated optics. Combining the flexibility of laser processing with liquid phase epitaxy we have fabricated and characterized lithium niobate channel waveguides on lithium niobate and lithium tantalate. We used liquid phase epitaxy with K2O flux on laser-machined lithium niobate and lithium tantalate substrates. The laser-driven rapid-prototyping technique can be programmed to give machined features of various sizes, and liquid phase epitaxy produces high quality single-crystal, lithium niobate channels. The surface roughness of the lithium niobate channels on a lithium tantalate substrate was measured to be 90 nm. The lithium niobate channel waveguides exhibit propagation losses of 0.26 ± 0.04 dB/mm at a wavelength of 633 nm. Second harmonic generation at 980 nm was demonstrated using the channel waveguides, indicating that these waveguides retain their nonlinear optical properties.

To maintain proteostasis, cells must integrate information and activities that supervise protein synthesis, protein folding, conformational stability, and also protein degradation. Extrinsic and intrinsic conditions can both impact on normal proteostasis, causing the appearance of proteotoxic stress. Initially, proteotoxic stress elicits adaptive responses aimed to restore proteostasis, allowing cells to survival the stress condition. However, if the proteostasis restoration fails, a permanent and sustained proteotoxic stress can be deleterious and cell death ensues. Many cancer cells convive with high levels of proteotoxic stress and this condition could be exploited in a therapeutic perspective. Understanding the cell death pathways engaged by proteotoxic stress is instrumental to better hijack the proliferative fate of cancer cells.

In this paper the dynamics of spatially extended infected phytoplankton with the Holling type II functional response and logistically growing susceptible phytoplankton system is studied. The proposed model is an extension of temporal model available [6], in spatiotemporal domain. The reaction diffusion system exhibits spatiotemporal chaos in phytoplankton dynamics. This is particularly important for the spatially extended systems that are studied in this paper as they display a wide spectrum of ecologically relevant behavior, including chaos. In this system stability of the system is studied with respect to disease contact rate and the growth fraction of infected phytoplankton indirectly rejoin the susceptible phytoplankton population. The results of numerical experiments in one dimension and two dimensions in space as well as time series in temporal models are presented using MATLAB simulation. Moreover, the stability of the corresponding temporal model is studied analytically. Finally, the comparison of the three types of numerical experimentations are discussed in conclusion.

The ability to read and quantify nucleic acids such as DNA and RNA using sequencing technologies has revolutionized our understanding of life. With the emergence of synthetic biology, these tools are now being put to work in new ways - enabling de novo biological design. Here, we show how sequencing is supporting the creation of a new wave of biological parts and systems, as well as providing the vast data sets needed for the machine learning of design rules for predictive bioengineering. However, we believe this is only the tip of the iceberg and end by providing an outlook on recent advances that will likely broaden the role of sequencing in synthetic biology and its deployment in real-world environments.

In cosmology, the cosmic curvature $K$ and the cosmological constant $\Lambda$ are two most important parameters, whose values have strong influence on the behavior of the universe. By analyzing the energy-momentum tensor and equations of state of ideal gas, scalar, spinor and vector potential in detail, we find that the total mass density of all matter is always positive, and the initial total pressure is negative. Under these conditions, by qualitatively analyzing the global behavior of the dynamical equation of cosmological model, we get the following results: (i) $K= 1$, namely, the global spatial structure of the universe should be a 3-dimensional sphere $S^3$. (ii) $0\le\Lambda < 10 ^ {-24} {\rm ly} ^ {-2}$, the cosmological constant should be zero or an infinitesimal. (iii) $a(t)>0$, the initial singularity of the universe is unreachable, and the evolution of universe should be cyclic in time. This means that the initial Big Bang is impossible at all. Since the matter components considered are quite complete and the proof is very elementary and strict, these logical conclusions should be quite reliable. Obviously, these conclusions will be much helpful to correct some popular misconceptions and bring great convenience to further research other problems in cosmology such as property of dark matter and dark energy.

Metallic nanoparticles (NPs), among polymeric NPs, liposomes, micelles, quantum dots, dendrimers, or fullerenes, are becoming more and more important due to their potential use in the novel medical therapies. Titanium dioxide (titanium(IV) oxide, titania, TiO2) is an inorganic compound that owes its recent rise in scientific interest to photoactivity. After the illumination in aqueous media with UV light, TiO2 produces an array of reactive oxygen species (ROS). The capability to produce ROS and thus induce cell death has found application in the photodynamic therapy (PDT) for the treatment of a wide range of maladies, from psoriasis to cancer. Titanium dioxide NPs were studied as photosensitizing agents in the treatment of malignant tumors as well as in photodynamic inactivation of antibiotic-resistant bacteria. Both TiO2 NPs themselves, as well as their composites with other molecules, can be successfully used as photosensitizers in PDT. Moreover, various organic compounds can be grafted on TiO2 NPs, leading to hybrid materials. These nanostructures can reveal increased light absorption allowing their further use in targeted therapy in medicine. In order to improve efficient anticancer therapy, many approaches utilizing titanium dioxide were tested. The most significant studies are discussed in this review.

The description of the microscopic world in quantum mechanics is very different from that in classical physics, and there are some points of view that are contrary to intuition and logic. The first is the loss of reality, the behavior of micro particles shows randomness and hopping. The second is the loss of certainty, the conjugate physical variables of a system cannot be determined synchronously, they satisfy the Heisenberg uncertainty principle. The third is the non-local correlation. The measurement of one particle in the quantum entanglement pair will change the state of the other entangled particle simultaneously. In this paper, some concepts related to quantum entanglement, such as EPR correlation, quantum entanglement correlation function, Bell's inequality and so on, are analyzed in detail. Analysis shows that the mystery and confusion in quantum theory may be caused by the logical problems in its basic framework. Bell's inequality is only a mathematical theorem, but its physical meaning is actually unclear. The Bell state of quantum entangled pair may not satisfy the dynamic equation of quantum theory, so it cannot describe the true state of microscopic particles. In this paper, the correct correlation functions of spin entanglement pair and photonic entanglement pair are strictly derived according to normal logic. Quantum theory is a more fundamental theory than classical mechanics, and they are not parallel relation in logic. However, there are still some unreasonable contents in the framework of quantum theory, which need to be improved. In order to disclose the real relationship between quantum theory and classical mechanics, we propose some experiments which show the wave-particle duality simultaneously and provide intuitionistic teaching materials for the new interpretation of quantum theory.

Key features of glycogen metabolism in excitable tissues are not well-explained by current concepts. Glycogen stores in brain and skeletal muscle are generally considered to function as local glucose reserves, to be utilized during transient mismatches between glucose supply and demand; however, quantitative measures show that blood glucose supply is likely never rate-limiting for energy metabolism in either brain or muscle under physiological conditions. These tissues nevertheless do normally utilize glycogen during intervals of increased energy demand, despite the availability of free glucose, and despite the ATP cost of cycling glucose through glycogen polymer. This seemingly wasteful shunt can be explained by considering the effect of glycogenolysis on the amount of energy derived from ATP (ΔG’ATP). ΔG’ATP is diminished by elevations in Pi, such as occur at sites of rapid ATP hydrolysis and net phosphocreatine consumption. Glycogen utilization counters this effect by sequestering Pi in glycolytic metabolites (glycogen_n + Pi → glycogen_n-1 + glucose-1-phosphate → phosphorylated glycolytic intermediates), and thereby maintains the amount of energy obtained from ATP at sites of rapid ATP consumption. This thermodynamic effect may be particularly important in the narrow, spatially constricted astrocyte processes that ensheath neuronal synapses. This effect can also explain the co-localization of glycogen and cytosolic phosphocreatine in brain astrocytes, glycolytic super-compensation in brain when glycogen is not available, and aspects of exercise physiology in muscle glycogen phosphorylase deficiency (McArdle’s disease).

RNA epigenetics is perhaps the most recent aspect of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combination whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes into RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging.

Nutrition is crucial for the management of patients affected by chronic kidney disease (CKD) to slow down disease progression and to correct symptoms. The mainstay of the nutritional approach to renal patients is protein restriction coupled with adequate energy supply to prevent malnutrition. However, other aspects of renal diets, including fiber content, can be beneficial. This paper summarizes the latest literature on the role of different types of dietary fiber in CKD, with special attention to intestinal microbiota and the potential protective role of renal diets. Fibers have been identified based on aqueous solubility, but other features, such as viscosity, fermentability, and bulking effect in the colon should be considered. A proper amount of fiber should be recommended not only in the general population but also in CKD patients, to achieve an adequate composition and metabolism of intestinal microbiota and to reduce the risks connected with obesity, diabetes, and dyslipidemia.

Plant male sterility refers to the failure in the production of fertile pollen. It occurs spontaneously in natural populations and may be caused by genes encoded in the nuclear (genic male sterility; GMS) or mitochondrial (cytoplasmic male sterility; CMS) genomes. This feature has great agronomic value for the production of hybrid seeds and has been widely used in crops, such as corn, rice, wheat, citrus, and several species of the family Solanaceae. Mitochondrial genes determining CMS have been uncovered in a wide range of plant species. The modes of action of CMS have been classified in terms of the effect they produce in the cell, which ultimately leads to a failure in the production of pollen. Male fertility can be restored by nuclear-encoded genes, termed restorer-of-fertility (Rf) factors. CMS from wild plants has been transferred to species of agronomic interest through somatic hybridization. Somatic hybrids have also been produced to generate CMS de novo upon recombination of the mitochondrial genomes of two parental plants or by separating the CMS cytoplasm from the nuclear Rf alleles

Persistent, non-explosive passive degassing is a common characteristic of active volcanoes. Distinct periodic components in measurable parameters of gas release have been widely identified over timescales ranging from seconds to months. The development and implementation of high temporal resolution gas measurement techniques now enables the robust quantification of high frequency processes operating on timescales comparable to those detectable in geophysical datasets. This review presents an overview of the current state of understanding regarding periodic volcanic degassing, and evaluates the methods available for detecting periodicity, e.g., autocorrelation, variations of the Fast Fourier Transform (FFT), and the continuous wavelet transform (CWT). Periodicities in volcanic degassing from published studies are summarised and statistically analysed, together with analyses of literature-derived datasets where periodicity had not previously been investigated. Finally, an overview of current knowledge on drivers of periodicity is presented and discussed in the framework of four main generating categories, including: (1) non-volcanic (e.g., atmospheric or tidally generated); (2) gas-driven, shallow conduit processes; (3) magma movement, intermediate to shallow storage zone; and (4) deep magmatic processes.

Organised hiking and trekking tours are promoted by many providers in adventure travel. Such guided tours shall be engaging for the tourists and evoke positive attitudes towards enjoying nature. We present the Trekking Engagement Profile as a tool to evaluate engagement factors of such guided tours, based on engagement research performed in a different domain, namely evaluating engagement in museums and science centres. This tool shall strengthen guides’ soft skills and enable them to increase engagement during an ongoing arrangement. For instance, the Trekking Engagement Profile can be applied when tourists indicate that the quality of a guided tour is not entirely to their liking. We show the viability of using the Trekking Engagement Profile in a small study with guides and participants of trekking tours offered by the Norwegian Trekking Association. Further, we offer guidance and charts to promote its practical use.

It is estimated that pancreatic cancer will be the 2^nd leading cause of cancer-related deaths globally by 2030, highlighting the ongoing lack of effective treatment options in this devastating condition. There is a lack of reliable prognostic or predictive markers in pancreatic cancer to guide management decisions, whether for systemic chemotherapy, molecularly targeted therapies, or immunotherapies. To date, the results for targeted agents and immunotherapies in unselected populations of chemo-refractory pancreatic cancer have not met expectations. The reasons for this lack of efficacy of immunotherapy in pancreatic cancer are incompletely understood. The challenges in pancreatic cancer include the physical barrier created by the dense desmoplastic stroma surrounding the tumor, chemokine-mediated exclusion of T cells, poor antigenicity, paucity of infiltrating T cells within the tumor, ultimately leading to an immunosuppressive microenvironment. A better understanding of the role of inflammation in pancreatic cancer, its tumor microenvironment and individualized patient-related features, be they molecular, clinical or histopathological would enable a more effective tailored approach to the management of pancreatic cancer. In this review, the role of inflammation, the immune tumor microenvironment and potential immune biomarkers in pancreatic cancer are explored.

The burnout syndrome, which affects so many healthcare workers, has recently awakened wide interest due to the severe repercussions related to its appearance. Even though job factors are determinant to its development, not all individuals exposed to the same work conditions show burnout, which demonstrates the importance of individual variables such as personality. The purpose of this study was to determine personality characteristics of a sample of nursing professionals based on the Big Five model, and then, having determined the personality profiles, analyze the differences in burnout and engagement based on those profiles. The sample was made up of 1236 nurses. An ad hoc questionnaire was prepared to collect the sociodemographic data, and the Brief Burnout Questionnaire, the Utrecht Work Engagement Scale and the Big Five Inventory-10 were used. The results showed that the existence of burnout in this group of workers, is associated negatively with extraversion, agreeableness, conscientiousness and openness to experience, and positively with the neuroticism personality trait. These personality factors showed the opposite pattern with regard to engagement. Three different personality profiles were also found in nursing personnel, in which professionals who had a profile marked by strong neuroticism and low scores on the rest of the personality traits where those who were most affected by burnout.

A overview on application of CO2 in the ironmaking and steelmaking process is presented. Study on resource utilization of CO2 is significant for the reduction of CO2 emissions and the coping with global warming. The paper introduces the research progress of CO2 utilization in the sintering, Blast Furnace, Converter, secondary refining, Continuous Casting and smelting process of stainless steel in recent years in China. According to the foreign and domestic research and application status, the paper analyzes the feasibility and metallurgical effects of the CO2 utilization in the ferrous metallurgy process. The paper mainly introduces such new techniques as 1) flue gas circulating sintering, 2) blowing CO2 through Blast Furnace tuyere and CO2 as a pulverized coal carrier gas, 3) top and bottom blowing CO2 in the converter, 4) Ladle Furnace and Electric Arc Furnace bottom blowing CO2, 5) CO2 as Continuous Casting shielding gas, 6) CO2 for stainless steel smelting, and 7) CO2 circulation combustion. CO2 has a very wide application prospect in ferrous metallurgy process and the quantity of CO2 utilization is expected to be 100kg per ton of steel. It will effectively facilitate the progress of metallurgical technology and strongly promote the energy conservation of metallurgical industry.

Neuroimmune semaphorin 4A (Sema4A), a member of semaphorin family of transmembrane and secreted proteins, is an important regulator of neuronal and immune functions. In the nervous system, Sema4A primarily regulates the functional activity of neurons serving as an axon guidance molecule. In the immune system, Sema4A regulates immune cell activation and function granting a fine tuning of immune response. Recent studies have shown a dysregulation of Sema4A expression in several types of cancer such as hepatocellular carcinoma, colorectal and breast cancers. Cancers have been associated with abnormal angiogenesis. The function of Sema4A in angiogenesis and cancer is not defined. Recent studies have demonstrated Sema4A expression and function in endothelial cells. However, the results of these studies are controversial as they report either pro – or anti-angiogenic Sema4A effects depending on the experimental settings. In this mini-review, we discuss these findings as well as our data on Sema4A regulation of inflammation and angiogenesis, which both are important pathologic processes underlining tumorigenesis and tumor metastasis. Understanding the role of Sema4A in those processes may guide the development of improved therapeutic treatments for cancer.

Recently, there have been revolutions in the development of both gene therapy and genome surgical treatments for inherited diseases. Much of this progress has been centered around hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple AAVs. CRISPR/Ca9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. New CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine FDA treatment trials.

Given the contradiction between the current demands for sustainability and the way the financial system works, this paper explores in a retrospective and a prospective view the Romanian Public Finance Sustainability, highlighting the major challenges and vulnerabilities. For the retrospective part, we concentrate mainly on empirical tests on Romanian government solvency between the period 1986- 2016, by applying unit root and co-integration tests. To gain a better, general understanding of the behavior of policy-makers, in the second part we use a scenario analysis of budgetary adjustment in the short and medium run under alternative hypotheses. The results provide a formal proof that policy makers decisions face critical and complex questions and the way in which they manage fiscal stimuli have a direct implication on the sustainability of the country and on the lax implementation of fiscal policy.

Macromolecular crystallography at cryogenic temperatures has so far provided the majority of the experimental evidence that underpins the determination of the atomic structures of proteins and other biomolecular assemblies by means of single crystal X-ray diffraction experiments. One of the core limitations of the current methods is that crystal samples degrade as they are subject to X-rays, and two broad groups of effects are observed: global and specific damage. While the currently successful approach is to operate outside the range where global damage is observed, specific damage is not well understood and may lead to poor interpretation of the chemistry and biology of the system under study. In this work, we present a phenomenological model in which specific damage is understood as the result of a single process, the steady excitation of crystal electrons caused by X-ray absorption, which acts as a trigger for the bulk effects that manifest themselves in the form of global damage and obscure the interpretation of chemical information from XFEL and synchrotron structural research.

Aflatoxins are a known cause of primary liver cancer in Mozambique since pre-independence epidemiological studies. However, their impact goes beyond the public health, affecting the country’s economy and raising legal concerns. As a developing country endemic for Aspergillus, the nation has been struggling to keep pace with external trade quality demands, delicate policy making, still dealing with the farmers’ limitations to control the contamination. The contamination shows variations over time, space and the different commodities. Considering the recommendations of the Codex Alimentarius, the major crops will be highly implicated unless there is major intervention from the authorities to control the toxins.

Since very few empirical endeavors have looked into statue and funerary art that represents social identities, this study aims to fill this gap. The research article aims to portray social status from the funeral arts, traditions and rituals. This longitudinal case study used interviews and a series of observations. The finding reveals that each funerary art represents particular class of noble families. Every funerary art also depicts specific insightful meaning for their noble families. The process of ritual and funeral ceremony is performed according to each status of noble families. This paper also describes the implication of the funerary art in social and cultural interactions.

Health information technology has been widely used in healthcare, which has contributed a huge amount of data. Health data has four characteristics: high volume; high velocity; high variety and high value. Thus, they can be leveraged to i) discover associations between genes, diseases and drugs to implement precision medicine; ii) predict diseases and identify their corresponding causal factors to prevent or control the diseases at an earlier time; iii) learn risk factors related to clinical outcomes (e.g., patients’ unplanned readmission), to improve care quality and reduce healthcare expenditure; and iv) discover care coordination patterns representing good practice in the implementation of collaborative patient-centered care. At the same time, there are major challenges existing in data-driven healthcare research, which include: i) inefficient health data exchanges across different sources; ii) learned knowledge is biased to specific institution; iii) inefficient strategies to evaluate plausibility of the learned patterns and v) incorrect interpretation and translation of the learned patterns. In this paper, we review various types of health data, discuss opportunities and challenges existing in the data-driven healthcare research, provide solutions to solve the challenges, and state the important role of the data-driven healthcare research in the establishment of smart healthcare system.

The purpose of this study is to explore the intensity of emotions and social skills in a physical education teaching unit (PE). Two instruments of analysis are used: the GES (Games and Emotion Scale) to evaluate emotions and an ad-hoc questionnaire to measure the social skills of 21 students in the sixth year of primary education. The data analysis was carried out using a generalised estimating equation model (GEE), taking into account the correlation between the different scores of the same subject and the asymmetry of the data. The results show positive emotions to be significantly more intense than negative ones and ambiguous emotions are revealed throughout all the PE sessions.

While traditionally people relinquish their pets to an animal shelter or pound, the internet provides a newer method to re-home. We analysed advertisements (ads) on the largest website in Australia for trading dogs and cats, gumtree.com.au. Data was collected in 2016. Dogs were sampled on February 7, 16 and 24, 2016 and cats on February 9, 19 and 26, 2016 with 2640 ads for relinquished dogs, and 2093 ads for relinquished cats. It was estimated >31,000 puppies/dogs and >24,000 kittens/cats are relinquished on gumtree.com.au per year. The median age of dogs was 1.42 and cats 0.9 years of age. There were 23% of dog ads and 62% of cat ads for free animals. Compared to the human population there were proportionately more ads in Queensland and fewer ads in Victoria. A total of 15 people were surveyed who had relinquished a dog or cat using gumtree.com.au. The dog owners used gumtree.com.au because they believed the shelters were full (n = 4), and; they wanted to see/interview the new owner (n = 2). For cat owners it was because they had originally got the cat on gumtree.com.au (n = 2); they use gumtree.com.au for other things, and it works (n = 2), and; they wanted to see/interview the new owner (n = 2). The data collected will be valuable for implementation of policy and interventions to protect the welfare of un-wanted dogs and cats.

The aim of the present study is to investigate both the performance and preferences of males and females Computer Science (CS) graduates. In order to attain the above goal, a quantitative case study was conducted regarding 89 degrees, acquired from 2006 to 2012, from the Department of Computer Science and Technology, University of Peloponnese, Greece. The analysis of the data revealed that in terms of performance, no significant differences between the mean grades of males and females exist, in almost most of the courses included in the curriculum of the aforementioned CS department. Any statistically significant differences in performances were present in almost equal number of courses in favor of males and females. It seems also, that females performed better in the courses they selected more than males. Regarding preferences, in CS courses, it seems that gender differences are existent. Males preferred more than females did core programming courses and advanced topics of Software Systems, computer networks, computer engineering, robotics and mathematics, whereas females preferred more the study of algorithms and security issues, computer fractals, data management, computer architecture, and mobile communication. In addition, females preferred courses in reference with humanities and social sciences, CS terminology, and career opportunities. Yet, females did not select any of programming lab-based courses, computer engineering, computer network issues and robotics.

Oil revenues and external debt might have stimulated economic growth in the oil exporting countries via investment in capital projects. The paper estimated economic growth on oil revenues and external debt after controlling public investment and population growth over the period 1970-2015. Following the confirmation of the order of integration, our analysis is based on autoregressive distributed lag bound testing to cointegration approach. The key findings are that oil revenues and public investment contributes to Nigeria’s economic growth. However, our findings also indicate that external debt and population growth retards growth. The study suggests that minimizing fiscal deficits and unnecessarily foreign loans by creating tax avenues through the development of the non-oil sectors would reduce the dependency syndrome on a single commodity (oil) in Nigeria.

Sports video analysis is an interesting and emerging field in the domain of computer vision. It has become a very popular subject among scholars all over the world in the last decade due to the need of automated classification of events such as offsides, in/out situations, goals and so on. The most important problem in sports video analysis is detection and tracking of ball and players. Extraction of court lines is also another important problem since it is necessary in the classification of aforementioned events. In this study, considering some of the previous work on the subject, we develop a method for tracking the ball and players in tennis videos where the camera position and orientation is supposed fixed.

The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. Therefore, the theory of oxidation-inflammation was proposed as the main cause of aging. Accordingly, the chronic oxidative stress, that appears with age, affects all cells and especially those of the regulatory systems, such as the nervous, endocrine, and immune systems and the communication between them. This prevents an adequate homeostasis and, therefore, the preservation of health. It was also proposed that the immune system plays a key role in the aging process, specifically in the rate of aging, since there is a relationship between the redox state and functional capacity of immune cells and longevity of individuals. Moreover, the role of the immune system in senescence could be of universal application. A confirmation of the central role of the immune system in oxi-inflamm-aging is that the administrationintake? of adequate amounts of antioxidants in the diet improves immune function, decreases their oxidative stress, and consequently increases longevity. The promotion of healthy lifestyles is one of the major goals of governments and international agencies all over the world. Human molecular processes are influenced by both physiological pathways and exogenous factors which include, for instance, those originating from diet. Dietary intake has substantive effects on molecular processes of metabolic health. Nutrients can directly regulate physiological changes in human body. In fact, in addition to have an energetic and structural value, nutritional intake provides bioactive molecules which are selectively able to modulate specific metabolic pathways, noticeably affecting cardiovascular and neoplastic diseases development or progress. Numerous bioactive nutrients are being progressively identified and their chemopreventive effects are being described at clinical and molecular mechanism levels. Systematic analyses comprise all “omics” technologies (such as transcriptomics, proteomics and metabolomics) and the goal is to investigate bioactive molecules effects derived from the diet. Nutrigenomic knowledge on physiologic status and disease risk will provide both developments of better diagnostic procedures and of new therapeutic strategies specifically targeted on nutritionally relevant processes. The present review was aimed to understand the molecular mechanisms underlying beneficial effects of bioactive nutrients and nutrigenomics on age-related diseases.

The objective of this research was to study the dynamics of moisture and nutrition at the root zone and to quantify the variables linked to efficient water management in avocado orchards of mid and high-lands of Michoacán, México, in typical Andisols of low fertility with (A)C(w2) and C(w2) climates, respectively. Using the FDR (Frequency Domain Reflectometry) technology, the dynamics of soil moisture and salinity were recorded daily at four depths: 0-15, 15-30, 30-45, and 45-60 cm. The soil moisture balance model was used to determine actual evapotranspiration (ETr), crop coefficient (Kc), and water use efficiency (WUE). Results indicated that ETr is 66-73% of the total water at 0-30 cm depth; the fertilizer absorption is limited to 0-30 cm, being negligible at deeper layers. The water use efficiency is 4.4 to 5.6 kg of fruit m-3 of applied water, and the ratio of the water use index (ETr/irrigation sheet applied, ISA) is 0.65-0.70; while the annual avocado Kc is 0.72 in Cutzato and 0.78 in Tiamba. We concluded that avocado has a low water requirement, it does not cause leaching of nutrients and/or water, the absorption of water and nutrients mostly occurs at 30 cm depth, and from a hydrological point of view, the crop is environmentally friendly.

Water resources worldwide are limited, especially in desert areas like Saudi Arabia. Therefore, the rational and sustainable management of irrigation water supply is an imperative required by the conditions of space and time. This study evaluates the irrigation system through partial root-zone drying (PRD) and regulated deficit irrigation (RDI). The effect of applying the PRD and RDI systems on the efficiency and rationalization of irrigation water consumption in a greenhouse and open field cucumber was studied in addition to using the surface (S) and subsurface (SB) drip irrigation methods on irrigation efficiency. The productivity of the RDI-S regular drip irrigation treatment was considered 100% as the control on which the results of all treatments are measured. The results showed that in terms of irrigation technique, the PRD-SB technique had the highest productivity during the winter season in greenhouse cucumbers, with a general average of 13.8 kg m-2 for all irrigation levels, while the RDI-SB technique had the highest productivity during the summer season, with a general average of 16.1 kg m-2. Regarding irrigation level results, the study showed that an irrigation level of 100% is the highest productivity in all irrigation techniques, with a general average of 14.9 kg m-2 for all irrigation techniques during the winter season and 16.4 kg m-2 during the summer. However, the increase in the irrigation level to 150% did not increase productivity. In comparison, the application of the deficit irrigation technique by reducing the level of irrigation to 50% was not accompanied by a similar decrease in productivity. The study results also showed that irrigation with the PRD-SB system was the most productive in the open field at all irrigation levels, with a general average of 7.3 kg m-2. The general average of the percentage decrease in productivity in all irrigation techniques compared to reducing the irrigation percentage to 50% and 75% was 22% and 3 %. The irrigation efficiencies were higher when applying the PRD (PRD-SB) in winter. In contrast, applying a deficit irrigation system (RDI-SB) in the summer season had the highest efficiency. It could be concluded that using PRD and RDI systems for indoor and outdoor cucumber can save irrigation water.

Health issues of children with intellectual disabilities (ID) have gained significant attention as a key focus of China health goals. This study aimed to compare the differences in displacement skills and problem behaviors among children with varying degrees and types of ID, while also exploring their relationship. The study included 90 participants who were children with ID and had completed TGMD-2 displacement skills and Strengths and Difficulties Questionnaire (SDQ) assessments. Covariance, partial correlation, and multiple linear regression analyses were conducted to examine the differences and correlations between these factors. The findings revealed that higher severity of intellectual disability was associated with lower scores in locomotor skills and increased manifestation of problem behaviors. Notably, there were significant variations in locomotor skills and problem behaviors among children with different types of intellectual disabilities. There is a positive correlation between locomotor skills and problem behaviors in children with intellectual disabilities, where locomotor skills can predict the occurrence of problem behaviors. In Conclusion, the research confirms that the development of locomotor skills can have a positive impact on the accompanying problem behaviors of children with developmental disabilities.

Contamination of soil and crops with heavy metals (HMs) poses a significant environmental challenge in the United States. Hence, this study aimed to assess HM contamination levels from sampled Ohio and West Virginia soils using various pollution indicators analyses, including Enrichment Factor (EF), Geo-accumulation index (lgeo), Contamination Factor (CF), and Pollution Load Index (PLI) and identify the Translocation Factor (TF) of HMs in the edible part of the vegetables and further evaluate health risks associated with dietary exposure through estimations of Estimated Daily Intake (EDI), Hazard Index (HI), Target Hazard Quotient (THQ), Cancer Risk (CR) and Target Cancer Risk (TCR) on adults and children. In this study, Fe was the most predominant contaminant, ranging from 28.41 to 67.36 g/kg in the soil. Cancer risk assessment revealed that Ni poses significant risks. Therefore, regular monitoring of metal concentrations in soil and vegetables grown in these regions might mitigate potential health hazards in the future.

The rise in prevalence of obesity in women of reproductive age in both developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health, contributing to substantial economic burden on society. Placental lipid metabolism might be disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism and handling from women with pre-gestational obesity as a sole pregnancy complication and compared to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidized products of docosahexahenoic acid (DHA), neuroprostanes, and arachidonic acid (AA), isoprostanes. Placental fatty acid transporters FABP1, FABP3 and endothelial lipase protein were measured. Despite no signs of overall alterations in lipid content, increased contents of DHA, AA, DHA-derived neuroprostanes and AA-derived isoprostanes and decreased content of FABP1 protein were found in placentas from obese women. Multivariate analyses suggested that these oxidised fatty acids are associated with maternal and placental inflammation and also with birth weight. These results might shed light on the molecular mechanisms associated with altered fatty acid metabolism and lipid handling in maternal pre-gestational obesity, placing these oxidized fatty acids as novel mediators of placental function.

The objective of this study was to determine the effects of supplementing L-isoleucine (L-Ile) on milk protein synthesis, using an immortalized bovine mammary epithelial (MAC-T) cell line. In this case, the cells were treated with 0, 0.3, 0.6, 0.9, 1.2 and 1.5 mM of supplemental Isoleucine (Ile), and the most efficient time for protein synthesis for each amino acid was determined by measuring the cell, medium and total protein at 0, 24, 48, 72 and 96 h. Confirmatory tests showed that 48h incubation time and 0.6 mM dosage of L-Ile are considered as the optimal time and dosage. The mechanism of milk protein synthesis was elucidated through proteomics analysis to clarify the metabolic pathway. When the L-Ile was supplemented, extracellular protein (medium protein) reached a peak at 48h, whereas in the case of the intracellular cell protein, it was shown to have reached to its peak at 24h in all L-Ile dosage treatments. In total, it is noted that there were 63 upregulated and 52 downregulated proteins. The results of the protein pathway analysis showed that the L-Ile group stimulated insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade, insulin/IGF pathway-protein kinase B signaling cascade, p53 pathway, de novo purine biosynthesis, Wnt signaling pathway, glycolysis, pentose phosphate pathway, and ATP synthesis which are pathways involved and related to protein and energy metabolism. Together, these results demonstrate that L-Ile supplementation was effective in stimulating β-casein synthesis by stimulating genes and pathways which are significantly related to protein and energy metabolism.

Deficit schizophrenia is characterized by leaky tight and adherens junctions and bacterial translocation. Here we examine whether (deficit) schizophrenia is accompanied by leaky paracellular, transcellular and vascular barriers in the gut and blood brain barriers. We measured IgA responses to occludin, claudin-5, E-cadherin and β-catenin (paracellular pathway, PARA), talin, actin, vinculin and epithelial intermediate filament (transcellular pathway, TRANS) and plasmalemma vesicle-associated protein (PLVAP, vascular pathway) in 78 schizophrenia patients and 40 controls. IgA responses to claudin-5, E-cadherin and β-catenin, the sum of the four PARA proteins and the ratio PARA/TRANS were significantly higher in deficit schizophrenia than in non-deficit schizophrenia and controls. A large part of the variance in PHEMN (psychosis, hostility, excitation, mannerism and negative) symptoms, psychomotor retardation, formal thought disorders, verbal fluency, word list memory, word list recall and executive functions was explained by the PARA/TRANS ratio coupled with plasma IgA responses to Gram-negative bacteria, IgM to malondialdehyde, CCL-11 (eotaxin), IgA levels of the ratio of noxious to more protective tryptophan catabolites (NOX/PRO TRYCATs) and a plasma immune activation index. Moreover, IgA levels to Gram-negative bacteria were significantly associated with IgA to E-cadherin, β-catenin and PLVAP, while IgA levels to claudin-5 were significantly predicted by IgA to E-cadherin, NOX/PRO TRYCAT ratio, Gram-negative bacteria and CCL11. The phenomenology of the deficit syndrome is to a large extent explained by the cumulative effects of lowered natural IgM, breakdown of the paracellular and vascular pathways, increased bacterial translocation, peripheral immune-inflammatory responses and indices of BBB breakdown.

Comparing to males, females require much more morphine to produce comparable levels of analgesia, suggesting a difference in the endogenous hyperalgesia and analgesia modulation between sexes. Aside from hormones, emerging evidence suggests sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and American College of Gastroenterology (ACG), up to 25 % of the population having visceral pain at any one time, and in the United States 10-15 percent of adults suffering from irritable bowel syndrome (IBS). Here we analyzed literatures on clinical reports of sex differences in visceral pain focusing on IBS, other form of bowel dysfunction and comorbidities, and summarized animal models that provided means to investigate the underlying molecular mechanisms in sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems all contribute to sex-dependent nociception and nociplasticity in the painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism.

Subacute rumen acidosis (SARA) is a prevalent issue in intensive livestock farming, particularly associated with high-concentrate diets. This study investigates the prevalence and impact of SARA in Greek dairy sheep farming and explores the use of computerized rumen colorimetry as a management and diagnostic tool for SARA in dairy sheep farms. Forty-two dairy sheep flocks were monitored regularly for rumen pH, milk composition, and milk yield over an approximately 9-month milking period. Computerized Rumen Mucosal Colorimetry was applied to 280 culled, aged ewes from these farms, with rumen wall samples taken for histological examination. SARA cases were identified in 19 farms (45%, n=48). Farms with SARA cases had lower milk fat levels, although milk yield was higher in these farms, while milk protein levels did not differ based on the SARA status of the farms. In culled ewes, rumen color was significantly associated with the farm's SARA status. Additionally, ewes from farms with more SARA cases exhibited increased thickness in the ruminal epithelium layers, particularly in the non-keratinized and total epithelium layers. In conclusion, SARA is a common disorder in the Greek dairy sheep industry, lowering the fat content of milk. The study suggests that computerized rumen epithelium colorimetry in aged culled ewes shows promise as a diagnostic tool for SARA in dairy sheep farms.

The population’s mobility in urban areas is a necessary variable in the modeling of risk scenarios caused by atmospheric contamination. The inclusion of this concept makes static models more dynamic while considering people within a city to be an entity with complex mobility processes. We propose a conceptual and methodological tool to make the representation of the social, economic and territorial components, as well as the patterns in the population´s mobility to delimitate risk areas for human health by exposure of contaminants. In the volatile organic compounds (VOC), benzene, ethylbenzene, toluene and xylene (BTEX) are amongst the most dominant substances in fugitive vapor emissions in gas stations (GS). In urban areas, the exposure to BTEX by residential proximity and proximity to other facilities, which cause intra-urban agglomeration, can impact and affect human health. This model seeks to facilitate the focalization, identification and prioritization of risk areas by BTEX environmental contamination. This article goes beyond de conceptual framework. It suggests methodological and instrumental aspects to be applied in other cities. The government agencies must consider these results when establishing rules, permissions and procedures to reduce environmental pollution for managing the risk in a complex urban environment.

Membrane gas absorption technology and solar-assisted regeneration system are two promising approaches to reduce high energy consumption associated with carbon dioxide capture from coal fired power plants. In the present study, a solar-assisted hollow fiber membrane contactor (SOL-HFMC) power plant is proposed to capture and desorb CO₂ in hollow fiber membrane contactors with the assistance of solar thermal collectors. Techno-economic assessment and sensitivity analysis of the proposed system is carried out in three studied locations with different weather conditions for a 580 MWe pulverized coal power plant. Research results show that, the output capacity and net efficiency of the SOL-HFMC power plant are significantly higher than those of the reference power plant regardless whether TES system is applied or not. In addition, CEI of the SOL-HFMC power plant with TES system is 4.36 kg CO₂/MWh, 4.45 kg CO₂/MWh and 4.66 kg CO₂/MWh lower than that of the reference power plant. The prices of membrane, vacuum tube collector and phase change material should be reduced to achieve lower LCOE and COR values. Specifically for SOL-HFMC power plant with TES system, the corresponding vacuum tube collector price shall be lower than 25.70 $/m² for Jinan, 95.20 $/m² for Xining, and 128.70 $/m² for Lhasa, respectively. To be more competitive than solar-assisted ammonia-based post-combustion CO₂ capture power plant, the membrane price in Jinan, Xining and Lhasa shall be reduced to 0.012 $/m, 0.015 $/m and 0.016 $/m for the sake of LCOE, and 0.03 $/m, 0.033 $/m and 0.034 $/m for the sake of COR, respectively. The findings can provide guidance for decision-making and risk management strategies.

The Drinking Water Directive (EU) 2020/2184 includes the parameter microcystin-LR, a cyanotoxin, which drinking water producers need to analyze if the water source has potential for cyanobacterial blooms. In light of the increasing occurrences of cyanobacterial blooms worldwide and given that more than 50 percent of the drinking water in Sweden is produced from surface water, both fresh and brackish, the need for improved knowledge about cyanotoxin occurrence and cyanobacterial diversity has increased. In this study a total of 98 cyanobacterial blooms were sampled in 2016-2017 and identified regarding their toxin production and taxonomical compositions. The surface water samples from freshwater lakes throughout Sweden including brackish water from 8 east coast locations along the Baltic Sea were analyzed for their toxin content with LC-MS/MS and taxonomic composition with 16S rRNA amplicon sequencing. Both the extracellular and the total toxin content was analyzed. Microcystin´s prevalence was highest with presence in 82% of blooms, of which as free toxins in 39% of blooms. Saxitoxins were found in 36% of blooms in which the congener decarbamoylsaxitoxin (dcSTX) was detected for the first time in Swedish surface waters at four sampling sites. Anatoxins were most rarely detected, followed by cylindrospermopsin, which were found in 6% and 10% of samples, respectively. As expected, nodularin was detected in samples collected from the Baltic Sea only. The cyanobacterial operational taxonomic unit (OTU) with the highest abundance and prevalence could be annotated to Aphanizomenon NIES-81 and the second most profuse cyanobacterial taxon to Microcystis PCC-7914. In addition, two correlations were found, one between Aphanizomenon NIES-81 and saxitoxins and another between Microcystis PCC-7914 and microcystins. This study is of value to drinking water management and scientists involved in recognizing and controlling toxic cyanobacteria blooms.

High-Performance Liquid Chromatography (HPLC) is an advanced analytical technique employed to separate, identify, and quantify components in complex mixtures. The method operates based on the differential affinities of sample molecules for the mobile and stationary phases within a chromatographic column. HPLC is recognized for its high resolution, accuracy, and efficiency, making it indispensable across various fields including pharmaceuticals, biotechnology, environmental analysis, and forensic science. The technique's adaptability to different detectors such as UV-visible, fluorescence, and mass spectrometry enhances its versatility and precision in analyzing a wide array of substances. Despite its advantages, HPLC presents challenges such as high operational costs, the need for specialized expertise, and susceptibility to contamination.Nonetheless, its role in modern analytical chemistry is pivotal, providing crucial insights and supporting developments in diverse scientific and industrial domains. This abstract encapsulates the core aspects of the article, highlighting the significance and applications of HPLC while also acknowledging its limitations.

The influence of polysialic acid (PSA) and sialic acid (SA) on the gut microbial community composition and metabolites in healthy human was investigated using a bionic gastrointestinal reactor. The results indicated that PSA and SA significantly changed the gut microbiota and metabolites in different degrees. PSA can increase the relative abundances of Faecalibacterium and Allisonella, whereas SA can increase those of Bifidobacterium and Megamonas. Both can significantly increase the content of short-chain fatty acids. The results of metabolome analysis showed that PSA can upregulate ergosterol peroxide and gallic acid and downregulate the harmful metabolite N-acetylputrescine. SA can upregulate 4-pyridoxic acid and lipoic acid. PSA and SA affect gut microbiota and metabolites in different ways and have positive effects on human health. These results will provide reference for the further development of PSA- and SA-related functional foods and health products.

In today's digital landscape, cybersecurity has become a priority, with attacks becoming increasingly sophisticated. Traditional security approaches are no longer enough, requiring a more dynamic and advanced response. In this context, integrating Artificial Intelligence (AI) and Machine Learning (ML) appears key to addressing this growing threat. However, despite their high effectiveness, there is a developed problem: the integration of various data sources and technologies for comprehensive protection. This article presents an in-depth review of integrating Artificial Intelligence and Machine Learning in cybersecurity, focusing particularly on Open Extended Detection and Response (Open XDR) technology. The literature review in this article was meticulously conducted with specific criteria in mind. It focused on sourcing peer-reviewed journals, authoritative cybersecurity publications, and recent conferences that primarily concentrate on the advancements in AI and ML within the cybersecurity domain, particularly from 2018 to 2023. This timeframe was chosen to ensure the inclusion of the most current and relevant developments in Open XDR technology, Intrusion Detection Systems, Endpoint Detection and Response, and Security Information and Event Management systems. Additionally, the review gave special attention to studies and reports highlighting practical implementations and real-world applications of these technologies, thereby ensuring a comprehensive understanding of their impact and effectiveness in enhancing cybersecurity resilience. The methodology used is a detailed literature review, examining how various cybersecurity components interact and function. These components include Intrusion Detection Systems (IDS), which monitor networks for malicious activities; Endpoint Detection and Response (EDR), which focuses on detecting and investigating security incidents on endpoints; and Security Information and Event Management (SIEM), systems that provide real-time analysis of security alerts. The review also considers the role of Active Directory, a directory service for Windows domain networks, and the process of log forwarding, where log files are transmitted to a central server for analysis, in the context of AI and ML. The paper delves into the development of AI and ML, underscoring their roles in cybersecurity for advanced data processing, pattern recognition, and predicting threats. It explores both supervised (where the model is trained on labeled data) and unsupervised learning (where the model learns from unlabeled data) in ML, and how these techniques bolster cybersecurity measures. The article highlights the significance of Open XDR as a critical innovation that integrates data from multiple sources for comprehensive security analysis. Further, the review discusses how the integration of AI and ML into various cybersecurity tools, such as IDS, EDR, and SIEM, augments capabilities in threat detection and response. It addresses the challenges and opportunities that AI and ML present in the cybersecurity domain, focusing on ethical issues, data privacy concerns, and the necessity for ongoing professional development in this rapidly advancing field. The paper concludes by affirming the effectiveness of merging AI and ML with these cybersecurity tools within the Open XDR framework.

This study assessed the perception and use of digital applications for soil fertility management and conservation strategies among small-scale crop farmers in southwest Nigeria. A total of 376 farmers were randomly selected across the six southwest states. The data collected were analyzed using descriptive statistics and Logit regression. Majority of the farmers relied on perception and other non-conventional approaches such as the appearance of weeds and performance of crops in the previous season to assess soil fertility. Only 1.1% and 0.3% of the farmers assessed soil fertility through soil test and digital application respectively. Most farmers adopted bush fallowing and the use of inorganic fertilizer to improve soil fertility. Although, 4.8% of the farmers indicated that they had digital application on their mobile phones, only 2.9% reported to have used such. More than half (56.4%) of the famers stated that lack of awareness of the existence of digital application and internet enabled telephones were reasons they have not been able to use digital applications. Majority of the farmers (97.3%) indicated their willingness to embrace the use of new farm decision digital application which can provide more information especially on soil fertility if introduced. Logit model results revealed that literacy level, membership of farmers’ association and extension contact significantly increased the likelihood of willing to use soil digital application, but older farmers are less likely to use digital application.

Hepatitis E virus (HEV) is a zoonotic foodborne virus with an annual infection prevalence of 20 million human cases, which seriously affects public health and economic development in both developed and developing countries. To better understand the epidemiology of HEV in the Centre of Portugal, a cross-sectional study was conducted from 2016 to 2023 with sera samples from wild ungulates. The seroprevalence and risk factors for HEV seropositivity were evaluated in the present study. Specifically, antibodies against HEV were determined by a commercial enzyme-linked immune-sorbent assay (ELISA). Our results show that in the 650 sera collected from 298 wild red deer and 352 wild boars from Portugal, 9.1% red deer (95% confidence interval [CI]: 6.312.9%) and 1.7% wild boar (95% CI: 0.63.3%) were positive for antibodies to HEV. Regarding age, the seropositivity in juvenile wild ungulates was 1.3% (95% CI: 0.273.72%) and 7.2% in adults (95% CI: 4.910.11%). Logistic regression models investigated risk factors for seropositivity. The odds of being seropositive was 3.6 higher in adults than in juveniles (95% CI: 1.7218.11%) and the risk was 4.2 higher in red deer than in wild boar (95% CI: 1.64–10.69%). Both wild ungulate species were exposed to HEV. The higher seroprevalence in red deer suggests that this species may have a major contribution to the ecology of HEV in the Centre of Portugal. Further research is important to understand how wildlife affects the epidemiology of HEV infection in Portugal.

Risedronate sodium (RIS) possesses very low bioavailability and several adverse effects in the gastrointestinal tract when administered through an oral route. Thus, this necessitates the need to develop novel formulation. Hence, we had developed RIS-HA-TCS loaded mPEG coated nanoparticles for the treatment of osteoporosis. Chitosan was used to synthesize thiolated chitosan and its characterization was done using DSC and FTIR. Ellman's reagent was used to measure the degree of thiol immobilization. The RIS-HA fabrication was done and was further conjugated with the synthesized TCS. The Box-Behnken design process was used for designing fifteen batches of RIS-HA-TCS nanoparticles, which were formulated by ionic gelation procedure in which tripolyphosphate (TPP) was used as a crosslinking agent. Moreover, RIS and RIS-HA-TCS in-silico activity was compared for farnesyl pyrophosphate synthetase enzyme. The obtained results revealed that the binding affinity of RIS was much more than the conjugated RIS. Successful docking results paved the way for thiolation of chitosan with RIS. The drug entrapment efficiency (%EE), particle size and Polydispersity index (PDI) of RIS-HA-TCS nanoparticles obtained were 85.4 ±2.21%, 252.1 ±2.44 nm and 0.2± 0.01 respectively. The particle size, PDI, and encapsulation efficiency of RIS-HA-TCS were reported to be 264.9 ±1.91 nm, 0.120± 0.01, and 91.1 ±1.17%, respectively, after being further conjugated with mPEG. TEM showed the spherical particle size of RIS-HA-TCS and RIS-HA-TCS-mPEG. The in-vitro release of RIS-HS-TCS-mPEG was found to be significantly higher (95.13±4.64%) as compared to RIS-HA-TCS (91.74 ± 5.13%), RIS suspension (56.12 ± 5.19%) and marketed formulation (74.69 ± 3.98%). In an ex-vivo gut permeation study, RIS-HA-TCS-mPEG nanoparticles was found to have an apparent permeability of 0.5858×10-1 cm/min which was better than the apparent permeabilities of RIS-HA-TCS formulation (0.4011 ×10-4cm/min), RIS suspension (0.2005 ×10-4 cm/min) and marketed preparation (0.3401 ×10-4 cm/min)..

Accurate measurement of solid precipitation (S) has a critical importance for proper understanding of the Earth’s hydrological cycle, validation of emerging technologies and weather prediction models, and developing parameterizations of severe weather elements such as visibility (Vis). However, measuring S is still a challenging problem mainly because of wind effects. The wind effects are normally mitigated by using a Double-Fence Automated Reference (DFAR) system to reduce the wind speed (Ug). To contribute towards addressing some of these issues we have analyzed data sets collected at a site located in Southern Ontario, Canada using several instruments. The instruments include two Geonor gauges, one placed inside a DFAR (SDFAR) and the other inside a double Alter shield (DASG), a Pluvio2 gauge inside a single Alter shield (SASP), a HotPlate, a PARSIVEL2 Disdrometer that measures S and fall velocity (V), and a FD12P senor that measures S and type and Vis. The results show that for the Ug observed in this study (Ug &lt; 6 ms-1), both DASG and SASP have similar collection efficiency (CE) of near 70%. The transfer functions (TF) for DASG and SASP as a function of Ug and also Ug, and V have been derived. The TF for the DASG that includes both Ug and V showed better agreement with observation than just Ug alone. The S measured using all the other instruments were correlated well with SDFAR, but the PARSIVEL2 and FD12P overestimated and underestimated the snow amount respectively as compared the SDFAR. However, the HotPlate captured similar amount of S as the SDFAR. According to this study, the SDFAR showed good correlation with Vis.

Research efforts toward Philippine biodiversity have increased significantly due to concerns about its natural resources and biodiversity. However, there is an imbalance in the distribution of published studies, with specific territories and organisms receiving more attention. Mindanao, a southern Philippine Island, is known for its high levels of endemism for amphibians and reptiles. Despite this, research on these groups remains unconsolidated. To address this gap, we conducted a biodiversity synthesis focusing on amphibians and reptiles in the faunal region of Mindanao. We found an increasing effort towards herpetofauna over the two decades, yet there is a clear bias in the effort towards amphibians compared to reptiles. In addition, we found that amphibians have a significantly higher species threat index than reptiles and all other vertebrate groups, regardless of ecological status. Yet, threatened herpetofauna species and those facing a greater number of threats are poorly studied, in general. Understanding the factors driving research biases in Mindanao and the Philippines is essential to allow us to redirect research efforts to the most needed areas, particularly to understudied and neglected taxa in Mindanao. This is especially urgent in the face of changing climate, where diverse communities of herpetofauna are at increased risk of extinction. Consequently, by bridging these gaps in biodiversity information, we can effectively contribute to the conservation and understanding of biodiversity in the region.

RNA interference is a highly conserved process in which non-coding small RNAs (sRNA) modulate gene expression at the post-transcriptional level influencing plant growth and development. Dicer-like (DCL), Argonaute (AGO) and RNA-dependent RNA polymerase (RDR) are the core elements involved in gene silencing and their gene families have been explored in many plants. However, these genes and their response to abiotic stresses have not yet been well in wheat. In this study, 82 AGO, 31 DCL, and 31 RDR genes were identified and phylogenetic analysis of these proteins showed that clustered into ten, four and four clades respectively. RNA-seq analysis revealed constitutive expression of AGO1, AGO9, and DCL2 family expression analysis in tissues under normal and stress conditions, whereas RDR1 which is known to engage in siRNA biogenesis showed higher expression levels in wheat leaf tissues. Our findings build the foundation for comparative genomics analyses of RNA silencing elements in cereal crops, as well as new insights into the functional complexity of RNA silencing in wheat stress responses, which is critical for understanding the processes underlying wheat stress responses.

The emergence of the SARS-CoV-2 Variant of Concern (VOC) Omicron has been characterized by an explosive number of cases in almost every part of the world. The dissemination of different sub-lineages and recombinant genomes also led to several posterior waves in many countries. The circulation of this VOC and its major sub-lineages (BA.1 to BA.5) was monitored in community cases and in international travelers returning to Venezuela, by a rapid partial sequencing method. The specific sub-lineage assignment was performed by complete genome sequencing. Epidemic waves of SARS-CoV-2 cases were observed among international travelers during 2022, a situation not seen before December 2021. The succession of the Omicron VOC sub-lineages BA.1 to BA.5 occurred sequentially, except for BA.3, which was almost not detected. However, the sub-lineages generally circulated two months earlier in international travelers than in community cases. The diversity of Omicron sub-lineages found in international travelers was related to the one found in the USA, consistent with the most frequent destination of international travel from Venezuela this year. These differences are compatible with the delay observed in Latin American countries in the circulation of the different lineages of the Omicron VOC.

The diet of the lionfish (Pterois miles), an invasive species in the Aegean Sea, was examined by collecting stomach content data from fish collected in three study sites in the Aegean Sea (southern Crete, Kastellorizo and Nysiros islands). Prey composition in terms of numerical abundance and frequency of occurence was used to compare lionfish’s diet between these sites. Lionfish largely preyed upon teleosts (5% to 83% numerical abundance and 16% to 59% frequency of occurrence depending on the site) and crustaceans (12% to 95% numerical abundance and 15% to 91% frequency of occurrence). The most important teleost families in lionfish’s diet were Gobiidae, Labridae, and Scorpaenidae, while decapods and especially the family Scyllaridae and the genus Plesionika were the dominant crustacean prey items. The lionfish was found to be an especially successful generalist across the study sites, an opportunistic, predatory species overall, and at the same time, at a local level, it seems to be an equally successful specialist that could increase the predation mortality of already stressed prey populations, and can be a serious threat to endemic, critically endangered, and/or commercially important species.

Plant Cysteine Oxidase (PCO) is a plant O2-sensing enzyme of catalyzing oxidation of cysteine to Cys-sulfinic acid at the N-termini of target proteins. To better understand the Brassica napus PCO gene family, PCO genes in B. napus and related species were analyzed. In this study, 20, 7 and 8 PCO genes were identified in Brassica napus, Brassica rapa and Brassica oleracea, respectively. According to phylogenetic analysis, the PCOs were divided into five groups: PCO1, PCO2, PCO3, PCO4 and PCO5. Gene organization and motif distribution analysis suggested that PCO gene family was relatively conserved during evolution. Expression analysis showed that PCO genes were expressed in different tissues at different developmental stages. Interestingly, most of the Bna/Br/BoPCO5 members were expressed in leaves, roots, flowers, buds and siliques, suggesting an important role in both vegetative and reproductive development. Expression of BnaPCO was induced by various abiotic stress, especially waterlogging stress, which was consistent with the result of cis-element analysis. In this study, the PCO gene family of Brassicaceae was analyzed for the first time, which contributes to a comprehensive understanding of the origin and evolution of PCO genes in Brassicaceae and the function of BnaPCO in regulating plant responses to abiotic stresses.

This study aimed to use remote sensing and GIS to detect changes in surface water and wetlands in the Kumasi Metropolis over a period of 20 years (2002-2022). Landsat images were processed using the QGIS software, and the Maximum Likelihood Algorithm was used to perform supervised classification of land use land cover, while raster calculator aided in detecting wetlands by calculation for NDWI, MNDWI, and AWEI. The results showed that the majority of the landscape in the Kumasi metropolis was made up of built-up areas (79.4%), followed by agricultural lands (13.3%) and wetlands (7.3%). Over the 20-year period, built-up areas had gained 20.7% of the total landscape, while agricultural lands and wetlands had lost 16.7% and 4.0%, respectively. All water index methods recorded an increase in non-water cover and a loss of water cover over the period, with surface water decreasing by 5% and non-water land cover increasing by 5%. The study concludes that there have been significant changes in wetlands and surface water land use and land cover within the Kumasi Metropolis over the past 20 years, and recommends the enforcement of legislation on surface water protection in the area to protect wetlands

Antimicrobial resistance (AMR) due to community carriage of antibiotic-resistant bacteria is highly prevalent in the WHO South-East Asia region. One of the major reasons is the misuse of antibiotics in animal farming practices and at community level, which threatens both human and animal health. However, this multifaceted One Health (OH) problem of antibiotic use (ABU) in poultry farms and respective farmers is not well studied in countries like Pakistan. Therefore, we conducted n OH cross-sectional study in rural Punjab to explore the current practices of ABU in poultry and poultry farmers, associated factors, their healthcare-seeking behaviour and biosecurity practices. We found all the participating farmers using antibiotics for poultry, 60% of which were Colistin sulphate and Amoxicillin trihydrate. The significant consumption of antibiotics in poultry farms (60%) and poultry farmers (50%) was without prescription. Most of the farms (85%) had no wastewater drainage system, causing direct shedding of poultry waste and antibiotic residue in the surrounding environment. Lack of farmers’ education, professional farm training and duration of farming experience were the significantly associated factors with ABU and knowledge of AMR. Our study implies the necessity of an integrated OH-AMR policy with the inclusion of farmers’ education, mass awareness, and strict antibiotic usage guidelines.

Emergence of multi drug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis poses a serious threat to TB control as the available treatment options are less effective in these cases. Therefore, new strategies are required for identification of new drugs and drug targets. The M. tuberculosis dihydrodipicolinate synthase is a putative drug target with no potent inhibitor. Here in this study, we have used a comprehensive computational approach to identify small molecule inhibitors and validated them in vitro. As similar structures tend to have similar functions, therefore 3 approaches, namely, (a) known inhibitor-based approach, (b) substrate analogues, (c) product analogues were used for compound screening from various chemical libraries. The fourth approach we have taken is fragment library screening.In vitro studies revealed that β-hydroxypyruvic acid tartronic acid are inhibitors of Mtb-rDapA with maximum inhibition 48% and 51% at 500µM concentrations respectively. We have also observed that β-hydroxypyruvic acid is a time dependent inhibitor of Mtb-rDapA. Further, thermal shift assays showed that β-hydroxypyruvic acid interacts with Mtb-rDapA and the thermal stability of Mtb-rDapA shifted by 3˚C. Among the product analogues of Mtb-DapA, dipicolinic acid showed to bind to Mtb-rDapB shifting thermal stability of Mtb-rDapB by 0.5˚C in binding. Additionally, we have designed a new approach by combining substrate and product analogues to achieve better inhibitions. In vitro assays validated that this combination approach increased maximum inhibition up to 100%. We envision that these compounds would serve as potent leads for tuberculosis drug discovery.

Autonomous systems and intelligent machines are involved in almost all areas of human activity and they are now more and more present in our everyday life. The reason for this extensive use certainly resides in all the benefits these machines offer to the users. In experimental settings, numerous studies have demonstrated the positive effects that the introduction of autonomous systems have on human decision-making and performance. However, studies have shown in addition that the introduction of these systems can have important negative effects as well. Considering that autonomous systems are now introduced in sensitive domains like the military or medicine, we need more than ever a comprehensive understanding of the effects they cause on human performance and decision-making, and particularly in tasks and contexts with a social or moral dimension. The aim of this narrative review is threefold. First, we will provide an overview of the main effects on a human agent’s decision-making and performance produced by the introduction of autonomous systems. Second, we will review the conditions identified as underlying factors of these effects, and see how current models of human – autonomous systems interaction integrate those conditions. Third, we will conclude this review by highlighting new directions for future investigations.

Background: Though tyrosine kinase inhibitors managed to reach outstanding responses in the treatment of Chronic Myeloid Leukemia, resistance is still a challenging point, occurring in approximately 10–20% of the cases, due to several mechanisms. STAT5 expression has been strictly linked to resistance and disease progression and may thus represent a significant target to overcome resistance to TKI in CML. The aim of the study is to explore the in vitro antineoplastic role of the STAT5 inhibitor Pimozide in association with 2nd and 3rd generation inhibitors on chronic myeloid leukemia cells. Methods: The cytotoxic effect was evaluated by the Trypan blue dye exclusion test. K562 cell lines were exposed to pimozide alone and in association with ponatinib and dasatinib at different concentrations to explore the drugs association effect and the in vitro cytotoxic concentrations. Conclusions: Pimozide showed a synergic effect when associated with ponatinib and dasatinib in survival inhibition of K562 cell lines. This results are of note and pave the way for a possible in vivo associations.

The City of Meycauayan is considered as one of the most polluted cities in the developing world on the account of industrial discharges of toxic materials to the environment. This work investigated the sources of the heavy metal pollution by analyzing soil and sediment samples for heavy metals (Cr, Hg, Ni, and Pb) together with selected environmental indicators (TN, TOM, and TP) located along the Meycauayan River. Hierarchical cluster analysis (HCA), principal components analysis (PCA), and Pearson correlation analysis (CA) were used to identify the sources of the metals. Results showed delineated locations of severe levels of heavy metal pollution downstream because of the concentration of industrial activities. Cr contributed more than any other heavy metals analyzed due to proliferation of tanneries discharging untreated wastewaters to the river. Significant inputs of Pb and Hg from Pb-acid battery recycling and gold smelting industries were also found. Risk assessments indicated severe levels of heavy metal pollution where industrial activities are concentrated. The mean Cr, Pb, Ni, and Hg in the sampling locations have mean incidences of toxicity of 91.7 %, 53.6 %, 27.7 %, and 70.0 %, respectively. Our study showed a serious need to address heavy metal pollution in Meycauayan.

Resistance training increases myofiber hypertrophy, but the morphological adaptations that occur within myofibers remain largely unresolved. Fifteen males with minimal training experience (24±4 years, 17.9±1.4 kg/m2 lean body mass index) performed 10 weeks of conventional, full-body resistance training (2x weekly). Body composition, the radiological density of the vastus lateralis muscle using peripheral quantitative computed tomography (pQCT), and vastus lateralis muscle biopsies were obtained one week prior to and 72 hours following the last training bout. Fiber typing and the quantification of myofibril and mitochondrial areas per fiber were performed using histology/immunohistochemistry (IHC) techniques. Relative myosin heavy chain and actin protein abundances per wet muscle weight as well as citrate synthase (CS) activity assays were also obtained on tissue lysates. Training increased whole-body lean mass, mid-thigh muscle cross-sectional area, various strength metrics, and mean and type II fiber cross sectional areas (fCSA) (p<0.05). Myofibril areas in type I or II fibers were not altered with training, suggesting a proportional expansion with fCSA increases. Relative myosin heavy chain and actin protein abundances also did not change with training. IHC indicated training increased mitochondrial areas in both fiber types (p=0.018). However, CS activity levels remained unaltered with training. Interestingly, although pQCT-derived muscle density increased with training (p=0.036), suggestive of myofibril packing, a positive association existed between training-induced changes in this metric and changes in type I+II myofibril areas (r=0.600, p=0.018). Shorter-term resistance training seemingly involves a proportional expansion of myofibrils and an accelerated expansion of mitochondria in type I and II fibers. Additionally, histological and biochemical techniques should be viewed independently from one another given the lack of agreement between the variables assessed herein. Finally, the pQCT may be a viable tool to non-invasively track morphological changes in muscle tissue.

The purpose of the study was to find the source of complaints and to diagnose dynamic upper respiratory tract problems, which were derived from the horse owners, trainers, and jockeys, and to evaluate the overground endoscopic examination efficiency to determine the subclinical upper respiratory tract (URT) abnormalities, which were unable to diagnose with resting endoscopy. In the study, overground endoscopy has been used which nowadays there is a more useful and safe technique of performing endoscopy during ridden exercise in the natural field to diagnose dynamic upper respiratory tract (URT) abnormalities in comparison with the more traditional method of resting endoscopy. This study focused on 25 racehorses (Thoroughbred, n:22 and Arabian n: 3), which were admitted to Racehorse Hospital with complaints of fade abruptly and/or abnormal respiratory noise during the last meters of the race. All horses were examined for the complaints to be associated with systemic disorders and/or lameness, the racehorses with lameness and/or systemic disorders findings were excluded. Resting (post-exercise) and overground endoscopy by using Dr. Fritz® ETL-Equine Overground Endoscopy was performed on a polytrack racecourse in all racehorses. Observed abnormalities were recorded as simple and complex cases and the results of resting and dynamic examination were compared. It was concluded the overground endoscopic examination has a useful diagnostic value in determining the cause of abnormal respiratory noise and/or fade abruptly.

Background Hokkaido is the northernmost, least populous, and coldest of the Japanese islands. It was the first prefecture to be affected by COVID-19, while Kanagawa is home to one of the most populous areas of Japan, namely the Tokyo metro area. The Japanese government responded early during the pandemic by identifying infected patients, contact tracing, and performing PCR analysis on anyone who was suspected of having been exposed to SARS-CoV-2. The government has also been publishing information about each individual who tested positive for the virus. Both Hokkaido and Kanagawa started recording COVID-19 cases in the winter of 2020 and have detailed records of thousands of patients, thus providing an invaluable resource for the transmission and behavior of the virus. Methods The current study analyzed the COVID-19 registry data from the Hokkaido and Kanagawa prefectures. The Hokkaido registry contained 1,269 cases (674 (53%) females and 595 (47%) males) recorded between February 14 and July 22, 2020. The Kanagawa registry had 3,123 cases (1,346 (43%) females and 1,777 (57%) males. The final data contained a total of 4,392 cases (2,020 (46%) females and 2,372 (54%) males). By leveraging the information on viral transmission paths available in the registry data, we performed exponential random graph model (ERGM) network analysis to examine demographic and symptomological homophilies of the SARS-CoV-2 viral transmission networks. Results We observed age, symptomatic, and asymptomatic homophilies in both prefectures. Furthermore, those patients who contracted the virus through secondary or tertiary contacts were more likely to be asymptomatic than those who contracted it from primary infection cases. The transmission networks showed that transmission occurred significantly in healthcare settings, as well as in families, although the size of the networks was small in the latter. Most of the transmissions stopped at the primary and secondary levels and no transmission beyond quaternary was observed. We also observed a higher level of asymptomatic transmission in Kanagawa than in Hokkaido. Conclusions Symptom homophilies are an important component of COVID-19 and suggest that nuanced genetic differences in the virus may affect its epithelial cell type range and can thus result in the diversity of symptoms seen in individuals infected by SARS-CoV-2. Moreover, environmental variables such as temperature and humidity may also be playing an important role in the overall pathogenesis of the virus.

The study focused on investigating the natural incidence of deoxynivalenol (DON) in corn and products from corn producing districts of Punjab, Pakistan. The analysis was carried out using HPLC with UV detector and immunoaffinity cleanup columns. The detection limit (LOD) and limit of quantification were 25 and 50 µg/kg, respectively. Total 1220 samples of corn and products were analyzed to detect the DON, and 539 (44.2%) samples were observed to be contaminated with DON (n ≥ LOD). Furthermore, 92 (7.5%) samples of corn & products have DON levels, elevated than the proposed limits of the EU. The data is significantly different from a normal distribution for DON in corn and products samples and from different locations (p < 0.05) for Shapiro-Wilk and Kolmogorov-Smirnov values. However, a significant difference in DON levels was found between corn and corn derived-products types (p ≤ 0.05). The lowest and highest exposure & hazard quotient (HQ) of 0.92 and 9.68 µg/kg bw/d were documented in cornflour samples.

Craniofacial neuropathic pain affects millions of people worldwide and is often difficult to treat. Two key mechanisms underlying this condition are a loss of the negative control exerted by inhibitory interneurons and an early microglial reaction. Basic features of these mechanisms, however, are still poorly understood. Using the chronic constriction injury of the infraorbital nerve (CCI-IoN) model of neuropathic pain in mice, we have examined the changes in the expression of GAD, the synthetic enzyme of GABA, and GlyT2, the membrane transporter of glycine, as well as the microgliosis that occur at early (5 days) and late (21 days) stages post-CCI in the medullary and upper spinal dorsal horn. Our results show that CCI-IoN induces a down-regulation of GAD at both postinjury survival times, uniformly across the superficial laminae. The expression of GlyT2 showed a more discrete and heterogeneous reduction due to the basal presence in lamina III of ‘patches’ of higher expression, interspersed within a less immunoreactive ‘matrix’, which showed a more substantial reduction in the expression of GlyT2. These patches coincided with foci lacking any perceptible microglial reaction, which stood out against a more diffuse areas of strong microgliosis. These findings may provide clues to better understand the neural mechanisms underlying allodynia in neuropathic pain syndromes.

We have shown that prebiotic xylo-oligosaccharides (XOS) increased beneficial gut microbiota (GM) and prevented high fat diet-induced hepatic steatosis, but the mechanisms behind these effects are not clear. We studied whether XOS affects adipose tissue inflammation and insulin signaling, and whether the GM and fecal metabolome explain associated patterns. XOS was supplemented or not with high (HFD) or low (LFD) fat diet for 12-weeks in male Wistar rats (n = 10/group). Previously analyzed GM and fecal metabolites were biclustered to reduce data dimensionality and identify interpretable groups of co-occurring genera and metabolites. Based on our findings, biclustering provides a useful algorithmic method for capturing such joint signatures. On the HFD, XOS-supplemented rats showed lower number of adipose tissue crown-like structures, increased phosphorylation of AKT in liver and adipose tissue as well as lower expression of hepatic miRNAs. XOS-supplemented rats had more fecal glycine and less hypoxanthine, isovalerate, branched chain amino acids and aromatic amino acids. Several bacterial genera were associated with the metabolic signatures. In conclusion, the beneficial effects of XOS on hepatic steatosis involved decreased adipose tissue inflammation and likely improved insulin signaling, which were further associated with fecal metabolites and GM.

Background: The methods used in low- and middle-income countries (LMICs) household surveys have not changed in four decades; however, LMIC societies have changed substantially and now face unprecedented rates of urbanisation and urbanisation of poverty. This mismatch may result in unintentional exclusion of vulnerable and mobile urban populations. We compare three survey method innovations with standard survey methods in Kathmandu, Dhaka, and Hanoi, and summarize feasibility of our innovative methods in terms of time, cost, skill requirements, and experiences. Methods: We used descriptive statistics and regression techniques to compare respondent characteristics in samples drawn with innovative versus standard survey designs and household definitions, adjusting for sample probability weights and clustering. Feasibility of innovative methods was evaluated using a thematic framework analysis of focus group discussions with survey field staff, and via survey planner budgets. Results: We found that a common household definition excluded single adult (46.9%) and migrant headed households (6.7%), as well as non-married (8.5%), unemployed (10.5%), disabled (9.3%), and studying adults (14.3%). Further, standard two-stage sampling resulted in fewer single adult and non-family households than an innovative area-microcensus design; however, two-stage sampling resulted in more tent and shack dwellers. Our survey innovations provided good value for money and field staff experiences were neutral or positive. Staff recommended streamlining field tools and pairing technical and survey content experts during fieldwork. Conclusions: This evidence of exclusion of vulnerable and mobile urban populations in LMIC household surveys is deeply concerning, and underscores the need to modernize survey methods and practices.

Phylogeny construction can help to reveal evolutionary relatedness among molecular sequences. The spike (S) gene of SARS-CoV-2 is the subject of an immune selective pressure which increases the variability in such region. This study aimed to identify mutations in the S gene among SARS-CoV-2 sequences collected in the Middle East and North Africa (MENA), focusing on the D614G mutation, that has a presumed fitness advantage. Another aim was to analyze the S gene sequences phylogenetically. The SARS-CoV-2 S gene sequences collected in the MENA were retrieved from the GISAID public database, together with its metadata. Mutation analysis was conducted in Molecular Evolutionary Genetics Analysis software. Phylogenetic analysis was done using maximum likelihood (ML) and Bayesian methods. A total of 553 MENA sequences were analyzed and the most frequent S gene mutations included: D614G=435, Q677H=8, and V6F=5. A significant increase in the proportion of D614G was noticed from (63.0%) in February 2020, to (98.5%) in June 2020 (p<0.001). Two large phylogenetic clusters were identified via ML analysis, which showed an evidence of inter-country mixing of sequences, which dated back to February 8, 2020 and March 15, 2020 (median estimates). The mean evolutionary rate for SARS-CoV-2 was about 6.5 × 10^-3 substitutions/site/year based on large clusters’ Bayesian analyses. The D614G mutation appeared to be taking over the COVID-19 infections in the MENA. Bayesian analysis suggested that SARS-CoV-2 might have been circulating in MENA earlier than previously reported.

The present study aims to evaluate the ability of peonidin and petunidin-3-glucoside (Peo and Pet-3-glc) and their metabolites (vanillic acid; VA and methyl-gallic acid; MetGA), to prevent monocyte (THP-1) adhesion to endothelial cells (HUVECs), and to reduce the production of VCAM-1, E-selectin and VEGF in a stimulated pro-inflammatory environment, a pivotal step of atherogenesis. Tumor necrosis factor-α (TNF-α; 100 ng mL-1) was used to stimulate the adhesion of labelled monocytes (THP-1) to endothelial cells (HUVECs). Successively, different concentrations of Peo-3-glc and Pet-3-glc (0.02, 0.2, 2 and 20 µM) and VA and MetGA (0.05, 0.5, 5 and 50 µM) were tested. After 24 h, the production of VCAM-1, E-selectin and VEGF was quantified by ELISA kits, while the adhesion process was measured spectrophotometrically. Peo-3-glc and Pet-3-glc (from 0.02 to 20 µM) significantly (p<0.0001) decreased THP-1 adhesion to HUVECs at all concentrations (-37%, -24%, -30% and -47% for Peo-3-glc; -37%, -33%, -33% and -45% for Pet-3-glc). VA, but not MetGA, reduced the adhesion process at 50 µM (-21%; p<0.001). At the same concentrations, a significant (p<0.0001) reduction of E-selectin, but not VCAM-1, was documented. In addition, anthocyanins and their metabolites significantly decreased (p<0.001) VEGF production. The present findings suggest, that while Peo-3-glc and Pet-3-glc, but not their metabolites, reduced monocyte adhesion to endothelial cells through suppression of E-selectin production, VEGF production was reduced by both anthocyanins and their metabolites suggesting a role in regulation of angiogenesis.

Milling and mining metal ores are major sources of heavy metal contamination. The Spring River and its tributaries in southeast Kansas are contaminated with Pb, Zn, and Cd as a result of 120 years of mining activities. Trace metal transformations and cycling in mine waste materials greatly influence their mobility and toxicity and affect plant productivity and human health. It has been hypothesized that under reduced conditions in sulfate-rich environments, these metals can be transformed into their sulfide forms, thus limiting mobility and toxicity. We studied biogeochemical transformations of Pb, Zn and Cd in flooded subsurface mine waste materials, natural or treated with organic carbon (OC) and/or sulfur (S), by combining advanced microbiological and X-ray spectroscopic techniques to determine the effects of treatments on the microbial community structure and identify the dominant functional genes involved in the biogeochemical transformations, especially metal sulfide formation over time. Samples collected from medium-, and long-term submerged columns were used for microarray analysis via functional gene array (GeoChip 4.2). The total number of detected gene abundance decreased under long-term submergence, but major functional genes abundance was enhanced with OC plus S treatment. The microbial community exhibited a substantial change in structure in response to OC and S addition. Sulfur-reducing bacteria genes dsrA/B were identified as key players in metal sulfide formation via dissimilatory sulfate reduction. Uniqueness of this study is that microbial analyses presented here in details are in agreements with molecular-scale synchrotron-based X-ray data supporting that OC-plus-S treatment would be a promising strategy for reducing metal toxicity in mine waste materials.

Extramammary Paget disease (EMPD) is an uncommon adenocarcinoma of apocrine gland-rich areas, presenting significant diagnostic challenges due to its nonspecific clinical appearance and frequent misidentification as benign, inflammatory skin conditions. Traditional diagnostic methods such as biopsy are invasive and uncomfortable, often required repeatedly due to high recurrence rates. Dermoscopy and non-invasive imaging techniques have been used but provide limited diagnostic accuracy due to their constraints in depth penetration and resolution. Recent advancements in imaging technologies, such as line-field confocal optical coherence tomography (LC-OCT), show promise in enhancing diagnostic precision while minimizing invasive procedures. LC-OCT merges high-resolution imaging with deep penetration capabilities, capturing detailed horizontal and vertical skin images akin to histopathology. This study evaluated the diagnostic performance of LC-OCT in detecting EMPD and its recurrence in 17 clinically suspicious anogenital regions, belonging to 6 patients. Data were collected prospectively at patient bedside by an LC-OCT expert with poor training for EMPD; and, then, reviewed retrospectively by an independent LC-OCT expert with adequate training for EMPD and no concerns about time. The prospective examination yielded 64.7%-accuracy, 71.4%-sensitivity, and 33.3%-specificity. The retrospective analysis achieved 94.1%-accuracy, 100%-sensitivity, and 66.7%-specificity, with the only false positive case being a difficult-to-diagnose concomitant presentation of a lichen sclerosus et atrophicus. Despite the need for specialized training, our results suggest that LC-OCT represents a valuable tool for accurately identifying EMPD and improve its management by reducing unnecessary biopsies. Further studies are needed to standardize its clinical application.

Many neurodegenerative diseases are directly related to the formation of toxic protein aggregates, such as Parkinson’s and Alzheimer’s diseases, which are associated with the aggregation of alpha-synuclein (α-syn) and beta-amyloid (Aβ ), respectively. In this context, protein fibrils are the hallmark of these neurodegenerative diseases. In this sense, planning or designing compounds that are capable of preventing or reducing the formation of protein aggregation in the brain can be of fundamental importance for the curative treatment of these diseases. This work presents an in silico and experimental study to investigate the inhibitory potential of the ligands Octovespin (bioinspired by the wasp venom Polybia Occidentalis) and Fraternine-10 (bioinspired by the wasp venom Parachartergus fraternus wasp) against the aggregation of fibrils of the peptides Aβ(17-42) and α-syn, respectively. Using molecular docking and molecular dynamics simulations with 100 ns, the disaggregation capacity of these ligands was studied. The results obtained indicate that Octovespin and Fraternine-10 interact with the Aβ and α-syn protein fibrils throughout the simulation time. The RMSD values and the interactions with amino acids responsible for fibril aggregation demonstrate that both Octovespin and Fraternine-10 have a significant disaggregation potential, which corroborates the observations in vitro and in vivo. Furthermore, experimental results of Fraternine-10 demonstrate an anti-aggregation effect, indicating that it can promote the disaggregation of fibrils and prevent them from aggregating again to form oligomers. These discoveries qualify these molecules as potential candidates to become medicines against Parkinson’s and Alzheimer’s diseases.

Chikungunya (CHIKV) and Mayaro (MAYV) viruses are arthritogenic alphaviruses that promote an incapacitating and long-lasting inflammatory muscle-articular disease. Despite studies pointing out the importance of skeletal muscle (SkM) in viral pathogenesis, the long-term consequences on its physiology after acute injury and the mechanism of persistence of symptoms are still poorly understood. Combining molecular, morphological, Nuclear Magnetic Resonance Imaging, and histological analysis, we conduct a temporal investigation of CHIKV and MAYV replication in a wild-type mice model, focusing on the impact on SkM composition, structure, and repair in the acute and late phases of infection. We found that viral replication and induced-inflammation promote fast loss of muscle mass and reduction of fibers cross sectional area, by inducing muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin expression, that trigger protein breakdown, resulting in acute SkM fibers atrophy. After temporal reduction of inflammation and clearance of infectious viral particles, SkM atrophy persists until the late phase of infection. The genomic CHIKV and MAYV RNAs were still detected in SkM at the late phase, along with increased levels of chemokines and anti-inflammatory cytokines expression. In agreement with the involvement of inflammatory mediators on induced atrophy, neutralization of TNF and the reduction of oxidative stress using monomethyl fumarate, an agonist of Nrf2, decreases atrogens expression and atrophic fibers, while increasing weight gain in treated mice. Taken together, these data indicate that arthritogenic alphavirus infection could chronically impact body SkM composition and also harm repair machinery, contributing to a better understanding of mechanisms of arthritogenic alphaviruses pathogenesis and with description of potentially new targets of therapeutic intervention.

Background and Objective: Patients with spinal muscular atrophy (SMA) treated with a dis-ease-modifying therapy (DMT) are often classified as responders or non-responders based on at-tainment of a specific improvement threshold on validated functional scales. This categorization may significantly impact treatment reimbursement in some countries. The aim of this research is to evaluate the perception of treatment benefit by patients considered as responder or non-responder. Methods: In this non-commercial multicenter study, 99 post-symptomatically treated SMA type I-III patients with a median age of 11.2 (0.39-57.4) years at treatment initiation were stratified into three groups based on their treatment outcomes, i.e. those exhibiting clinically significant improvement (N=41), those with non-clinically significant improvement (N=18), or those show-ing no improvement (N=40). Fifteen months after treatment initiation patients or patients’ care-givers were assessed using a patient-rated scoring system based on the Patient Global Impression of Change (PGIC) scale, comprising 22 questions targeting important aspects and tasks in the daily life of patients with SMA. Results: We found no statistical difference in patient perception of treatment benefit in 17 out of 22 domains across patient groups. Conclusion: Our results suggest that functional motor scales do not recapitulate patients and pa-tients’ caregivers experience about the effect of nusinersen treatment in SMA.

Environmental degradation leads to a totally unsustainable food system. In addition to this is-sue, the consumption of foods that improve people's health and well-being is recommend-ed. These guidelines create new challenges and the demand for alternatives to meet these needs in the short term. One of the alternatives is undoubtedly the use of by-products of winemaking, namely in the form of grape pomace flour (GPF), which is obtained in a totally sustainable way, requires no further water consumption or agricultural land, and is an ingredient that boasts all the characteristics that meet the circular economy and has colossal potential in promoting nutrition and healthy eating. To verify the benefits of using the Touriga Nacional and Arinto (Vitis vinifera L.) flour varieties, analytical determinations were made to identify and quantify different components, such as nitrogen and extractable phosphorus, ash, moisture, proteins, fats, dietary fibers, total sugars, and phenolic content. GPF could become a valuable ingredient due to its nutritional quality and high content in various polyphenols namely flavonoids and pyranoanthocyanins.

Foods that are fermented have a crucial role in global diets, these foods benefit from the process of fermentation, which enhances nutrition, flavor, and safety through the use of probiotics, anti-aging compounds, and antibiotics. Traditional fermentation is based on the spontaneous activity of microorganisms, while modern methods utilize defined cultures for consistency. The microorganisms in cheese are important for the flavor and texture of the product. These microorganisms are either non-starter or starter bacteria, yeast, and mold. The advances in sequencing technology have facilitated an increase in our understanding of these communities and their contribution to the quality and safety of cheese. Despite the health benefits of fermented dairy products, such as yogurt, they can pose a risk of contamination with pathogens. New methods of management and sequencing are crucial to ensuring the safety and quality of fermented foods, combining traditional methods with modern advances.

This study investigates the critical factors of trust, commitment, and adaptation within supplier relationship management (SRM) in the context of e-commerce. Through qualitative research methods, including semi-structured interviews and documentary analysis, the study explores how these factors influence relationship dynamics and organizational outcomes in digital business environments. Trust is examined as foundational to effective SRM, encompassing integrity, reliability, and shared values between buyers and suppliers. Commitment is analyzed in terms of long-term orientation, resource allocation, and relationship-specific investments aimed at mutual growth and sustainability. Adaptation emerges as essential for navigating the dynamic e-commerce landscape, encompassing proactive strategies, flexibility, and innovation to respond to market changes and technological advancements. The findings highlight the interplay and mutual reinforcement among trust, commitment, and adaptation, contributing synergistically to relationship resilience and organizational performance. However, challenges such as information asymmetry, cybersecurity risks, and organizational inertia are identified as barriers to effective SRM. Practical implications include strategies for enhancing trust, fostering commitment, and cultivating adaptive capabilities through continuous learning, collaborative innovation, and technology integration. By integrating these insights, businesses can strengthen supplier relationships, drive sustainable growth, and achieve competitive advantage in the digital economy.