Parkinson's disease (PD) is the second most common neurodegenerative disorder, entailing several motor-related symptoms that contribute to a reduced quality of life in affected subjects. Recent advances in wearable technologies and computing resources have shown great potential for the assessment of PD-related symptoms. However, the potential applications (e.g., early diagnosis, prognosis and monitoring) and key features of digital biomarkers for motor symptoms of PD (DB-MS-PD) have not been comprehensively studied. This study aims to provide a state-of-the-art review of current digital biomarker definitions for PD, focusing on the use of wearable devices. This review systematically examines research articles from 2012 to 2024, focusing on key features and recent technologies in PD research. A total of 22 studies were included and thoroughly analyzed. Results indicate that DB-MS-PD can accurately distinguish patients with PD (PwPD) from healthy controls (HC), assess disease severity or treatment response, and detect motor symptoms. Large sample sizes, proper validation, non-invasive devices, and ecological monitoring make DB-MS-PD promising for improving PD management. Challenges include sample and method heterogeneity and lack of public datasets. Future studies can leverage evidence of the current literature to provide more effective and ready-to-use digital tools for monitoring PD.

This study investigates the moderating role of information asymmetry in shaping the effect of environmental sustainability reporting on the firm value of listed manufacturing companies in Nigeria. Utilizing an ex-post facto research design, the study draws on a stratified sample of 29 manufacturing firms from a population of 43 listed on the Nigerian Exchange as of December 31, 2022. Spanning from 2007 to 2022, the study collects secondary data from annual reports, Nigerian All Share Index reports, meristem securities and register platform Admin platform and sustainability reports. Employing descriptive and inferential statistics, along with multiple regression techniques, the analysis considers Firm value as the dependent variable, Environmental sustainability reporting as independent variables, Information asymmetry (IA) as the moderating variable and Equity ratio, Return on asset and Leverage as control variables. Results indicate that information asymmetry shows a negative and significant effect on the relationship between environmental sustainability reporting and firm value. The study concluded that information asymmetry impacts firm value despite environmental disclosure efforts. The study recommends that Nigerian manufacturing companies should engage in comprehensive disclosure practices to enhance transparency and address information asymmetry through adequate stakeholder engagement. The study’s findings emphasized the need for Nigerian policy makers to enhance regulations on environmental sustainability reporting. By implementing stricter disclosure laws and standards, policy can reduce information asymmetry and foster a more transparent business environment. This could attract foreign investment and demonstrate Nigeria’s commitment to sustainable practices. Furthermore, the study also highlights the importance of transparency in maintaining stakeholder trust. Improved disclosure practices can increase public trust in the manufacturing sector, promoting corporate responsibility. This heightened transparency benefits investors and the broader community, ensuring companies are accountable for their environmental impacts, ultimately leading to better environmental stewardship and community welfare.

ABSTRACT After locavore was chosen as “the best word of the year” in 2007, its popularity increased gradually. Today great number of locavores consciously prefer locally produced food for the benefit of themselves and their community. Undoubtedly this conscious movement has its consequences in marketing discipline. Accordingly, this paper is purposed to examine the how locavore perceptions affect loyalty towards retailers that sell locally produced food. In this context, a survey was applied to people residing in Istanbul and Kocaeli districts to measure the robustness of these effects. Furthermore, attitude towards locavore is used as a control variable to reveal to what extend locavorism affects these proposed connections. According to results, for participants with low attitude, Social Responsibility and Health Consciousness variables have significant effect on local retailer shopping loyalty. However, for participants with high attitude, all independent variables proved to have substantial effect on local retailer shopping loyalty. As the first empirical study in Turkey on the subject, this paper will provide important insight to academia and practicioners due to today’s ever-increasing consciousness in green marketing.

The teaching of mathematics at the Faculty of Military Technology of the University of Defense in the first two years of the five-year Military master’s degree is divided into the teaching of students in four specializations: Military Technologies – Mechanical, Military Technologies – Electrical, Military Geography and Cartography, and Cybersecurity. The article discusses the previous five-year experience in teaching the subjects Mathematics I, Mathematics II, Mathematics III, and Graph theory for the specialization in Cybersecurity, that the author of the paper gained while teaching, as a guarantor of these four subjects. The article provides an overview of the topics that are covered, typical exam assignments, and an evaluation of the results of the semester exams in the five years since the accreditation of the Cybersecurity specialization was granted.

With continuous increase in integration of the semiconductor devices, the requirements on size accuracy and surface quality of the etched lead frame are higher. The etchant is a key factor on etching process and etched surface quality, while effects of the difference in etchants on microscopic etched surface morphology of the Cu alloy have not been directly studied. In this study, the aqua regia, acidic FeCl3 and CuCl2 solutions were used as etchants, and the CuCrSn alloy specimens with different microstructure were etched and characterized. The results show that the etching rate in aqua regia is high, and the grain orientation, grain boundary (GB) and dislocation have significant influence on the local etching rate. The preferential etching of some atomic planes forms steps between grains with different orientations, and the preferential etching around the GB and dislocation group forms grooves, resulting in high surface roughness. For etching of the FeCl3 and CuCl2 etchants, the steps and grooves become blurred, and almost invisible on the surface etched by the CuCl2 etchant, thus the surface roughness is much lower. The CuCrSn alloy surface etched by the aqua regia is clean, with little Cr-rich particles, while high density Cr-rich particles are remained on the surfaces etched with the FeCl3 and CuCl2 etchants. For the same kind of etchant, the ion concentration can affect the etching mechanism and etching surface morphology.

The implementation of Emissions Trading System (ETS) poses significant challenges for the Indian maritime sector. This paper investigates the regulatory implications of ETS, focusing on how these regulations impact compliance and operational practices within the Indian shipping sector. It also analyzes the economic effects, including the financial burden and competitive dynamics faced by the Indian shipping companies in a global context. Additionally, the paper explores various adaptation strategies, emphasizing technological innovations and operational adjustments essential for navigating ETS requirements. By integrating recent industry data and case studies, this study offers a comprehensive overview of how the Indian shipping industry can effectively address the evolving regulatory landscape of ETS.

The SI unit of length, the Metre, is presently defined by taking the fixed numerical value of the fundamental constant `c', the invariant speed of light in vacuum. This definition has the same physical basis as the previous definition, as the length of the path travelled by light in vacuum during a time interval of 1/299 792 458 of a second. With the atomic standard second defined in terms of the ground state hyperfine transition in Caesium-133, this definition is supposed to provide a universally reproducible standard of length. However, this relies on Einstein's singular postulate that the relative velocity of light in vacuum is an invariant constant that is independent of any inertial motion of the reference laboratory. I argue that the basis of the definition of the standard metre should be changed to the specific form, "the length of the path equal to the two-way propagation of light in vacuum during a time interval of 1/299 792 458 of a second", to be compatible and consistent with the fact that it is only the two-way relative velocity that is consistent with being an invariant. The null result in the Michelson-Morley two-way experiment, and in all such experiments to date, is consistent with a Galilean one-way propagation of light (relative velocity $c'=c\pm v$) as well as an invariant relative velocity of light. All practical methods and protocols related to the implementation of length standard involve also a two-way propagation, not conforming to the present definition. Besides, this redefinition is absolutely necessary because the relative velocity of light in one-way propagation is indeed Galilean, and not an invariant, as proved here in multiple ways including a direct experiment.

A quantum theory of gravity is among the most pursued goals in physics. I present a definitive and direct experimental proof that refutes the widely believed hypothesis of quantum gravity. The detections of astrophysical gravitational waves (GW) are inferred from the differential oscillations of suspended mirrors of optical interferometers like the aLIGO detectors. If gravity is indeed quantized, then the average energy $\bar{E}$ in the minute oscillations of the mirrors, at a frequency $\nu$, corresponds to the absorption of an integer number $N$ gravitational quanta with total energy $E_{gw}=Nh\nu$. The coherent and coincident detections across large separations of detectors, and also the constraint of the equivalence principle, dictate that the average number of quanta $\bar{N}$ forcing the oscillations obeys $\bar{N}\gg 1$, or $1/\sqrt{\bar{N}}\ll 1$. However, the average energy $\bar{E}$ in the differential oscillations is smaller than the energy of a single quantum of GW radiation at the detected astrophysical GW frequencies. This startling finding implies that $\bar{N} <1$, which is physically impossible if gravity is quantized. This singular contradiction refutes the long-held hypothesis that gravity is quantized.

as the growth and popularity of technology has become simultaneous ascend in both impacts and numbers of cyber criminals thanks to the web. For many years, the organization has strived in ways of preventing any attacks from cyber-criminal with advanced techniques. Cybercriminals and intruders are developing a more advanced way to breach the security surface of an organization. Advanced Persistent Threats are also known as APT are new and a lot more sophisticated version for multistep attack scenarios that are known and are targeted just to achieve a goal most commonly undercover activities. this report, there will cover everything I know that tells us about APT with more word and brief explanations

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.

Climate change poses a significant threat to European security, implicitly to Romania’s naval forces in the Black Sea. Rising sea levels, extreme weather events, and ocean acidification impact maritime operations, infrastructure, and personnel, with potential ramifications for regional stability. This paper explores the implications of climate change for the Romanian Navy and proposes "Green Defence" strategies to enhance resilience and sustainability. These strategies encompass energy efficiency, renewable energy integration, sustainable procurement, and the application of advanced functional materials in naval operations and infrastructure. By adopting a proactive and multifaceted approach, the Romanian Navy can adapt to the changing climate, ensuring operational effectiveness while minimizing environmental impact. This approach aligns with broader European security concerns and contributes to a more sustainable and resilient defence posture in the face of climate-related challenges.

During the last decades, zebrafish (Danio rerio) has become one of the most important model organisms to study different physiological and biological phenomena. Research field of carbonic anhydrases (CAs) and carbonic anhydrase related proteins (CARPs) is not an exception in this. The best-known known function of CAs is the regulation of acid-base balance. However, studies performed with zebrafish, among others, have revealed important roles for these proteins in many other physiological processes, some of which have been unpredicted in the light of the previous studies and suggestions. Examples are roles in zebrafish pigmentation as well as motor coordination. Disruption of the function of these proteins may generate even lethal outcomes. In this review, we summarize the current knowledge of CA-related studies performed in zebrafish.

Amidst increasing awareness of diet-health relationships, plant-derived bioactive peptides are recognized for their dual nutritional and health benefits. This study investigates bioactive peptides released after Alcalase hydrolysis of protein from chachafruto (Erythrina edulis), a nutrient-rich South American leguminous plant, focusing on their behavior during simulated gastrointestinal digestion. Evaluating their ability to scavenge radicals, mitigate oxidative stress, and influence immune response biomarkers, the study underscores the importance of understanding peptide interactions in digestion. Methods included previous enzymatic hydrolysis with Alcalase to obtain peptides, and results show significant radical scavenging and oxidative stress protection by chachafruto peptides. These findings highlight the potential of chachafruto bioactive peptides in functional foods and nutraceuticals, supporting human health through dietary interventions.

The Aβ cascade and alternations of biomarkers in neuro-inflammation, synaptic dysfunction and neuronal injury followed by Aβ have progressed. But the question is how to use the biomarkers. Here, we examine the evidence and pathogenic implications of protein interactions and the time order of alternation. After the deposition of Aβ, the change of tau, NfL and NG is the main alternation and connection to others. The neuro-inflammation, synaptic dysfunction and neuronal injury function is exhibited prior the structural and metabolic changes in the brain following Aβ deposition. The time order of such biomarkers compared to the tau protein is not clear. Despite the close relationship between biomarkers and plaque Aβ deposition, several factors favor one or the other. There is an interaction between the proteins that CSF SNAP-25, VILIP-1 and YKL-40 can predict the brain amyloid burden. The Aβ cascade hypothesis could be the pathway, but not all subjects are converted to AD, even with very high elevated Aβ. The interaction of biomarkers and the time order of change require further research to identify the right subjects and right molecular target for precision medicine therapies.

Since the 1960s, forest planners have used linear programming models to develop management plans for large, forested areas. Hundreds of academic papers have presented such models, incorporating multiple objectives, a growing diversity of management interventions, and uncertainty, among other things. Three basic ways to formulate these models have been used: Model I, III, and III. We define these models based on the sequence of management unit states represented by the variables. In Model I, variables represent a sequence of states from the beginning of the planning horizon to the end. In Model II, variables represent a sequence of states from one intervention to the next. Finally, in Model III, variables represent a single arc in a management unit’s decision tree, including only a beginning and an ending state. We formulate each type of model for a case study with three increasingly complex scenarios incorporating additional ecosystem services. Our results indicate that, despite requiring more variables and constraints, Model III requires the least time to formulate, largely because it has the least dense parameter matrix. Model II has the shortest solution times, with Model III close behind. Model I requires both the longest formulation and solution times.

Background and Objectives: Due to huge demand and availability of Banana, innovative cost effective method is necessary to promote and smoothen the banana production among farmers commercially mitigating the demand. Method and Materials: In this study, we feed cow dung mixture along with Urea, TSP, MoP, water to the distal part of rachis after cutting down male bud as soon as the female flowers matured into fruits (T1). The effect of this method was then compared with two control groups; one with the same strategy except fertilizer applied on root following ring method (C1, Positive control) and another was male flower untouched without applying fertilizer on rachis or root (C2, Negative control). Results and Conclusion: T1 showed more than double increase in length than controls. In the same way, in case of shape (diameter), T1 (0.46 cm) showed twice as better growth in the C1 (0.22 cm) and C2 (0.18 cm). Trend analysis showed the test group T1 curve is much steeper than the control groups suggesting faster growth rate than the other two. Finally, the cost of fertilizers for T1 per plant was estimated 0.091 USD while for positive control C1 it was 2.9 USD. This study shows an approach to be effective and economic comparing to traditional method of fertilizer application, which can be adapted as a new method of banana production.

Keywords: Marine Coasts; Protected Areas; Defense and Conservation; Asbestos Cement Materials; Wastes; Contamination; Human Health Risk; Medical Geology.

This paper presents a comprehensive analysis of the financial factors and risk management strategies essential for optimizing disaster resilience within the Serbian defence industry's critical infrastructure. The significance of this sector is multi-faceted, impacting national security, economic stability, and technological advancement. Primarily, the Serbian defence industry ensures the preservation of vital defence interests, maintaining Serbia's independence from foreign sources for weapons and military equipment in both peacetime and wartime. Economically, it is a significant employer of the working-age population, directly affecting local employment rates, fostering economic development, and ensuring the sustainable growth of this crucial sector. This, in turn, stimulates broader economic activity and enhances social cohesion while strengthening the national balance of payments through increased export potential. From a technological perspective, the defence industry drives scientific, technological, and industrial development, reinforcing Serbia's global political and military standing within the Western Balkans and on the international stage. Consequently, the paper aims to examine the risk management and protection of the Serbian defence industry's critical infrastructure, offering concrete and actionable measures to improve and develop these systems with a particular emphasis on security. The research's utility and contribution lie in identifying similarities and differences in the operational performance of defence industry companies, a vital segment of the national economy. The presentation of these findings focuses on the protection of critical infrastructure. The results will form the basis for further investigation into the underlying causes of business performance and the effective management of critical infrastructure security.

When we talk about the Defence Industry (DI), arms transfers, and military expenditures we mostly refer to data accumulated by the Stockholm International Peace Research Institute (SIPRI). In the SIPRI Top 20 list of largest exporters of major arms for 2019, small states hold consecutive positions: Israel takes 8th place, Switzerland is 13th, and Sweden, Norway, and Belarus place 15th, 17th, and 20th respectively. The author analyses the Swiss DI case due to several reasons; its place in SIPRI Top, its sharp rise of Swiss arms exports in the recent year, its Swiss neutrality strategy, the country’s multilingual society, and its all-government approach to the arms industry, though still contributing to the limited scholarly studies on contemporary Swiss DI. This paper aims to explore Swiss DI and its strategies, to identify the country’s defence and security policy influence towards DI, and to discuss the Swiss DI stance and future perspectives in the context of the global arms trade. At the same time, this paper also highlights Swiss DI successes and failures that could be of significant use to other small states aiming to develop or enhance their relevant DIs.

Quantum nonlocality represents correlation properties between subsystems of a composite quantum system, usually including the four types: Bell nonlocality, steerability, entanglement, and quantum correlation (quantum discord). Given a basis $e_{AB}=\{|e_{ij}\>\}_{i\in[d_A],j\in[d_B]}$ for the Hilbert space $\H_A\otimes \H_B$ of a bipartite system $AB$, a density operator $\rho^{AB}$ (quantum state) of $AB$ can be represented as a $d_Ad_B\times d_Ad_B$ matrix $\hat{\rho}_{e_{AB}}=[\]$, called the density matrix of a density operator $\rho^{AB}$. A natural question is what is the relationship between the quantum nonlocality of a density operator $\rho^{AB}$ and its corresponding density matrix $\hat{\rho}_{e_{AB}}$? In this work, we discuss the relationships between quantum locality and basis, and prove that one type of quantum locality of density operators and that of their density matrices under a basis are the same if and only if the chosen basis is the tensor product of the bases of subsystems. Consequently, different bases define different quantum nonlocality density operators.

Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has high infectivity in humans, attributed to the strong affinity of its spike (S) protein to human angiotensin-converting enzyme 2 (ACE2). Here, we analyzed the structural similarity of the S protein between SARS-CoV-2 and other SARS-related coronaviruses (CoVs). Methods We performed multiple alignment analysis of nine amino acid sequences of CoV S proteins from NCBI with MAFFT web-based software, followed by phylogeny analysis. Three-dimensional structure modeling was performed by SWISS-MODEL. We calculated the template modeling score between the S protein of SARS-CoV-2 and that of other SARS-related CoVs. Results The S1 domain of the unclassified CoV RaTG13 (the host of which is the intermediate horseshoe bat) was structurally very similar to that of SARS-CoV-2, implying that RaTG13 could be the origin of SARS-CoV-2. In addition, the folding property of the entire S protein was nearly the same between SARS-CoV-2 and RaTG13 after the PRRA amino acid insertion was removed from SARS-CoV-2. Conclusions RaTG13 could have a high binding affinity to ACE2, similar to SARS-CoV-2, and it is therefore highly likely to infect other animals. Therefore, massive research and monitoring of CoVs in animals is necessary to prevent future COVID-19-like disasters.

Directed energy deposition (DED) parameters were determined for near-β alloy Ti-55511 by employing statistical design of experiments (DOE) methods. Parameters resulting in fully dense freeform deposits were identified using two sequential DOEs. Single laser tracks were printed with several laser power, traverse rate, and powder feed rate settings in an initial DOE to identify promising build parameters. Capture efficiency and effective deposition rate were used to characterize and rank the single track deposits. The best parameters were then used to print solid cube with various X-Y and Z-overlaps (different hatch spacing, HS, and layer thickness, ZS) in a second DOE. Suitable deposition parameters were selected based on cube density and microstructure and were used to fabricate larger tensile samples for mechanical testing. Multiple parameter sets were found to provide dense Ti-55511 deposits with acceptable mechanical properties and parametric models showed statistical significance.

Axon guidance is a crucial process for growth of the central and peripheral nervous systems. In this study, 3 axon guidance related disorders, namely- Duane Retraction Syndrome (DRS) , Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS) and Congenital fibrosis of the extraocular muscles type 3 (CFEOM3) were studied using various Systems Biology tools to identify the genes and proteins involved with them to get a better idea about the underlying molecular mechanisms including the regulatory mechanisms. Based on the analyses carried out, 7 significant modules have been identified from the PPI network. Five pathways/processes have been found to be significantly associated with DRS, HGPPS and CFEOM3 associated genes. From the PPI network, 3 have been identified as hub proteins- DRD2, UBC and CUL3.

The aim of the study was to examine the biogas and methane yield of maize silage, a wastes in agricultural point of view and compare it to the biogas productivity of commonly used mixture of maize silage and mixed fodder with water. The experimental study was carried out into 2 parts. Firstly, the batch experiment was conducted in Mesophilic conditions (35°C), at five different hydraulic retention times (HRT): 6 DAT, 11 DAT 20 DAT 29 DAT and 41 DAT. The results revealed that maize silage was generated the highest biogas yield of 537 mL /241 mL at the HRT of 6days /41 days. Mixed fodder produced the highest biogas yield of 421 mL at the HRT of 6th days and the lowest one was 252 mL at the HRT of 20th days. Finally, the methane, carbon dioxide and hydrogen sulphide of biogas produced from maize silage and mixed fodder were analyzed using a gas chromatography. The results shown that biogas from maize silage precedes the gas less than the mixed fodder. In the field level experiment proved that from mixed fodder produced gas which would be enough for 7 member’s family used 3 months for the purpose of their cooking.

The Septoria Leaf Blotch Complex (SLBC), caused by the two ascomycetes Zymoseptoria tritici and Parastagonospora nodorum, can reduce global yearly yield of wheat by up to 50%. In the last decade in Italy, SLBC incidence has increased; notably, durum wheat has proven to be more susceptible than common wheat. Field fungicide treatment can efficiently control these pathogens, but it leads to the emergence of resistant strains and adversely affects human and animal health, and the environment. Our previous studies indicated that active compounds produced by Trametes versicolor can restrict the growth of mycotoxigenic fungi and the biosynthesis of their secondary metabolites (e.g. mycotoxins). Specifically, we identified Tramesan: a 23 KDa -heteropolysaccharide secreted by T. versicolor that acts as a pro-antioxidant molecule in animal cells, fungi, and plants. Foliar-spraying of Tramesan (3.3 µM) in SLBC-susceptible varieties of durum significantly diminished symptoms of Stagonospora Nodorum Blotch (SNB) and Septoria Tritici Blotch (STB) by 75% and 65%, respectively. Tests were conducted under controlled conditions as well as in field. We show that Tramesan elicits wheat defence against SNB and STB augmenting the synthesis of defence-related hormones, notably JA and SA, that in turn switch on the expression of markers of defence (PR1, PR4 inter alia). In field experiments, yield of durum wheat plants treated with Tramesan was similar to that of untreated ones. The results suggest the use of Tramesan for protecting durum wheat against SLBC.

Plants have a natural protective process of altering their genetic molecules in response to changing environments. To uncover the genetic potential of plants, it is crucial to understand how they adapt to adverse conditions by analyzing their genetic molecules. In the study, we focused on understanding the responsive genes of tomatoes under drought conditions. We analyzed RNASeq data from different Tomato genotypes, tissue types, and different drought durations. We used a time series scale to identify early and late drought-responsive gene modules and applied a machine learning method to identify the best responsive genes. We found six candidate genes of Tomato (ASCT, FLA2, BAG5, DCL2b, NFP7.3, and ADC1) that were responsive to drought. We further constructed their protein-protein interaction network to identify their potential interactors and found them drought responsive proteins. The candidate genes can help to explore the adaptation of tomato plants under drought conditions. The identification of these candidate genes and modules can have far-reaching implications for molecular breeding and genome editing in Tomato, providing insights into the molecular mechanisms that underlie drought adaptation. This research underscores the importance of the genetic basis of plant adaptation, particularly in changing climates and growing populations.

A comprehensive study of the interactions of human serum albumin (HSA) and α-1-acid glycoprotein (AAG) with two isoquinoline alkaloids: allocryptopine (ACP) and protopine (PP) was performed. The UV-Vis spectroscopy, molecular docking, competitive binding assays, and circular dichroism (CD) spectroscopy were used for the investigations. The results showed that ACP and PP form spontaneous and stable complexes with HSA and AAG, with ACP displaying a stronger affinity towards both proteins. Molecular docking studies showed also revealed the preferential binding of ACP and PP to specific sites within HSA, with site 2 (IIIA) being identified as the favored location for both alkaloids. This was supported by competitive binding assays using markers specific to HSA's drug binding sites. Similarly, for AAG, a decrease in fluorescence intensity upon addition of the alkaloids to AAG/ Quinaldine Red (QR) complexes indicated the replacement of the marker by the alkaloids, with ACP showing a greater extent of replacement than PP. CD spectroscopy showed that the proteins’ structures remained largely unchanged suggesting that the formation of complexes did not significantly perturb the overall spatial configuration of these macromolecules. These findings are crucial for advancing the knowledge on the natural products-protein interactions and the future design of isoquinoline alkaloid-based therapeutics.

Age-related diseases place an intense and growing stress on healthcare systems. Numerous theories of ageing exist. Yet prediction, prevention and treatment limitations of age-related disease persist because we lack a complete aetiological understanding of their origins. Here we propose a new theory that aims to provide a blueprint-type understanding of ageing and disease aetiology, working across multiple scientific disciplines. Supported by specific examples, we demonstrate that the primary driver of much of age-related diseases is the futile triggering of specific molecular pathways in a pathological manner, which we term patho-pathways. Patho-pathways induce pathological cell, tissue and system changes in the form of hyperactivity (undesirable increased and new biological activities that are typical of age related disease). As part of patho-pathways, all wild-type (normal) genes have the potential to contribute to age-related diseases (though specific risk varies and can be formularised). In a domino-style effect, one patho-pathway typically triggers others, resulting in complex, but traceable, cascades. Utility, in terms of changing clinical and scientific practice, is derived from mapping these cascades to create Blueprint Maps that allow identification of biomarkers and therapeutic targets far upstream in the causal chain of events. Finally, our theory provides testable hypotheses concerning predictions of links between otherwise seemingly disparate diseases as well as new interventions into ageing.

Reservoirs created by damming rivers significantly modify the environment and problems may arise: the storage of nutrients and organic matter in reservoirs often leads to decreased water quality due to eutrophication. Reservoirs built on lowland rivers are exposed to significant nutrient loads, often leading to eutrophication. In this article, the Sulejów Reservoir, in Central Poland, was the subject of the research, which focused on the use of Sentinel-2 remote sensing data to detect phytoplankton blooms, and on understanding the pattern of wind-driven surface currents using the CCHE2D model (a depth-averaged hydrodynamic model). The calculation of the total phosphorus load has shown that the reservoir mainly acts as nutrient storage. Still, during the low flow and intensive phytoplankton bloom, it can be a source of nutrients. The distribution of phytoplankton bloom on the Sulejów Reservoir was documented using eight Sentinel-2 satellite images from the vegetation season of 2020 and the Normalized Difference Chlorophyll Index (NDCl). Coupling remote sensing data and numerical modelling helps to interpret the hydrodynamic model results and understand nutrients and sediment dynamics within the reservoir. Hydrodynamic modelling combined with remote sensing data can be a valuable tool for selecting appropriate locations for water quality measurements at monitoring stations.

The maritime industry contributes to over 80% of global trade and ranks as the sixth-largest emitter of greenhouse gases. The International Maritime Organization has taken strides to reduce these emissions, while the European Union spearheads efforts to establish sustainable maritime transport. However, meeting decarbonisation targets poses significant challenges, with the potential implications of adopting an EU Emission Trading System (ETS) on shipping allowances, particularly at specific borders. If not managed effectively, this could result in diversifying regular container shipping routes away from EU ports, potentially leading to increased shipping emissions and disrupting the logistics trade and security chain. These challenges are exacerbated by the International Maritime Organization's lack of a carbon fee on bunkering, which creates an imbalance. The ETS Directive has fostered unfair competition between EU and non-EU ports due to discrepancies in applying emission unit allowances. It is imperative to implement preventive measures to contain and prevent the shift of operations from EU ports to nearby ports, ensure equitable treatment of EU transhipment ports and their competitors, and thwart carbon leakage. Additionally, the recent Houthis attacks on the Red Sea have significantly impacted shipping costs on the Cape of Good Hope route to Europe, necessitating increased allowances to and from Europe.

The maritime industry contributes to over 80% of global trade and ranks as the sixth-largest emitter of greenhouse gases. The International Maritime Organization has taken strides to reduce these emissions, while the European Union spearheads efforts to establish sustainable maritime transport. However, meeting decarbonisation targets poses significant challenges, with the potential implications of adopting an EU Emission Trading System (ETS) on shipping allowances, particularly at specific borders. If not managed effectively, this could result in diversifying regular container shipping routes away from EU ports, potentially leading to increased shipping emissions and disrupting the logistics trade and security chain. These challenges are exacerbated by the International Maritime Organization's lack of a carbon fee on bunkering, which creates an imbalance. The ETS Directive has fostered unfair competition between EU and non-EU ports due to discrepancies in applying emission unit allowances. It is imperative to implement preventive measures to contain and prevent the shift of operations from EU ports to nearby ports, ensure equitable treatment of EU transhipment ports and their competitors, and thwart carbon leakage. Additionally, the recent Houthis attacks on the Red Sea have significantly impacted shipping costs on the Cape of Good Hope route to Europe, necessitating increased allowances to and from Europe.

Metallo-β-lactamases (MBLs) are members of the structurally conserved but functionally diverse MBL-fold superfamily of metallohydrolases. MBLs are a major concern for global health care as they efficiently inactivate β-lactam antibiotics, including the “last-resort” carbapenems, and no clinically suitable inhibitors are currently available. Increasingly, promiscuous β-lactamase activity is also observed in other members of the superfamily, including from viruses, which represents an underexplored reservoir for future pathways to antibiotic resistance. Here, two such MBL-fold enzymes from Bacillus phages, the cyclic mononucleotide-degrading proteins ApycGoe3 and ApycGrass, are shown to efficiently degrade β-lactam substrates in vitro. In particular, ApycGrass displays a distinct preference for carbapenem substrates with a catalytic efficiency that is within one order of magnitude of that of the clinically relevant MBL NDM-1. Mutagenesis experiments also demonstrate that the loss of a metal-bridging aspartate residue reduces nuclease activity up to 35-fold, but improves carbapenemase activity. In addition, we propose that the oligomeric state significantly influences β-lactamase activity by modifying access to the active site pocket. Together, these observations hint at a possible new avenue of resistance via the spread of phage-borne MBL-fold enzymes with β-lactamase activity.

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

Companies operating in the PayTech and online e-commerce sectors play a crucial role in critical infrastructure, functioning within the dynamic digital landscape. This study focuses on the recovery process after cyber-attacks and examines the contrasting perspectives of internal and external professionals. The research reveals notable differences in the perceptions of recovery strategies between internal stakeholders such as investor relations, reputation management, and Chief Information Security Officers, representing companies belonging to critical infrastructure and external auditors, who provide just and emergency support and perform specific tasks. Importantly, the study underscores the current attitudes towards future information security strategies and their influence on the financial recovery and reputation of reliable companies following cyber incidents. This research contributes to the existing knowledge by shedding light on the perspectives of both a company's internal and external specialists involved in the recovery process and cyber resilience strategies in critical infrastructure sectors.

SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induce the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted in the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions which share high identity between SARS-Cov-2 anti-gens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals.

Staphylococcus aureus mastitis remains a major challenge for dairy farming. Here, 24 mice were immunized and divided into four groups: G1: control; G2: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) DNA vaccine; G3: F0F1 ATP synthase subunit α (SAS), succinyl-diaminopimelate (SDD), and cysteinyl-tRNA synthetase (CTS) recombinant proteins; and G4: SAS+SDD+CTS plus GM-CSF DNA vaccine. The lymphocyte subpopulations and the intracellular interleukin-17A (IL-17A) and interferon-γ production in the draining lymph node cells were immunophenotyped by flow cytometry. The immunophenotyping and lymphocyte proliferation was determined in spleen cells cultured with and without S. aureus stimulus. Immunization with S. aureus recombinant proteins generated memory cells in draining lymph nodes. Immunization with the three recombinant proteins plus GM-CSF DNA led to an increase in the percentage of IL-17A+ cells among overall CD44+ (memory), T CD4+, CD4+ T CD44+ CD27-, γδ TCR, γδ TCR+ CD44+ CD27+ and TCRVγ4+ cells. Vaccination with S. aureus recombinant proteins associated with GM-CSF DNA vaccine downregulates TH2 immunity. Immunization with the three recombinant proteins plus the GM-CSF DNA led to a proliferation of overall memory T, CD4+ and CD4+ TEM cells upon S. aureus stimulus. This approach fostered type 3 immunity, suggesting the development of a protective immune response against S. aureus.

An experiment was carried out at Nabogram Khamarbari, near the Manannogor, Sadar Upazila, Noakhali District, Noakhali-3814, Bangladesh during the period from 12th January 2018 to 17th April 2018, with two varieties of tomatillo (Physalis ixocarpa Brot.) SAU tomatillo-1 and SAU tomatillo-2. It was laid out in RCBD method having three replications and was conducted to observe the influence of staking and non-staking on tomatillo cultivation in coastal areas. For the study, growth indicating characters like no. of leaves plant^-1, size of leaf plant^-1, height of each plant, no. of branches plant^-1 and yield attributing parameters such as days to first flowering, days to 50% flowering, no. of fruits branch^-1, fruit weight and yield were obtained from the plants with the treatments of staking and non-staking. A wide variation was observed between two varieties of tomatillo with the effect of these treatments. According to the results highest no. of leaves branch^-1, maximum size of leaves branch^-1, tallest height of each plant, uppermost no. of branches plant^-1, highest no. of fruits branch^-1, maximum weight of each fruit and yield were obtained in the staking treatment over the non-staking treatment of SAU tomatillo-1 and in case of SAU tomatillo-2, with the same parameters the result indicated significantly upper in the staking treatment over non-staking treatment. Considering the two varieties of tomatillo, the outcome were significantly superior with staking treatment for the similar parameters. The findings of the experiment indicated that the best yield (21 tha¹) and highest financial benefit could be obtained by SAU tomatillo-1 and the best tomatillo production in saline soil of coastal areas is possible by cultivating SAU tomatillo-1.

There are ~200.000 households living in the detached houses and ger (yurt) with the small-coal stove which burns a raw coal in the Ulaanbaatar city. The proper heating system and improvement on the energy efficiency of residential dwellings is vital important for Ulaanbaatar city to reduce an air pollution as well as for the operation of current central energy system. This study shows the experimental results of two Gers with two different heating system and different thermal insulation. Technical availability of the system consisting of ETS heater with daytime charging schedule and areal PV system is also examined by using a simulation of MATLAB programming. As a result of the experiment, the indoor comfort level and energy efficiency of the Ger with added insulation and ETS heater with nighttime charging was enhanced to compare with the reference Ger. The Ger with added insulation and ETS heater consumed 3169 kWh for electric appliances and 5989 kWh for the heating season. The simulation was resulted that the ETS heater to be installed in the Ger 2 had prospected to increase the PV self-consumption rate by 76% because of the daytime charging schedule of ETS heater. The PV system supplied 31% of the total energy consumption with remained 69% of the main grid.

Spider silks, renowned for their exceptional mechanical and biocompatible properties, offer significant potential as scaffolds in tissue engineering. This paper explores the feasibility of using spidroins, the primary proteins in spider silk, to develop scaffolds that closely mimic the extracellular matrix (ECM) essential for tissue regeneration. Spidroins (spider silk proteins) are particularly valuable due to their unique strength, elasticity, and biocompatibility, which support cellular growth and differentiation. The paper examines current methods for producing recombinant spider silk, including using unicellular hosts like E. coli and multicellular systems like transgenic plants and silkworms. It also examines current scaffolds that utilize spidroins and their shortcomings, such as immunogenicity and protein production, which must be urgently addressed for more practical and effective widespread biomedical applications. In addition, it stresses the need for further research to solve these challenges and fully realize the potential of spider silk in biomedical applications.

Background: There is considerable evidence to support the association between environmental tobacco smoke (ETS) exposure and children’s burden of disease. However, literature on the health outcomes of prenatal ETS exposure among Chinese children has not yet been comprehensively reviewed. Objective: This systematic scoping review examines the currently available evidence and identifies gaps for further research on the health consequences of prenatal ETS exposure among Chinese children. Methods: Following the JBI scoping review methodological framework, we conducted a computer-aid search of three electronic databases-- PubMed, EBSCOhost, and ProQuest to include studies from January 2011 to May 2023 that addressed the health outcomes of Chinese children whose mothers were exposed to ETS at any stage of the pregnancy. Further, a methodological quality assessment of the selected articles was conducted, using JBI Critical Appraisal Checklists. Results: A total of 30 articles were reviewed, including eleven high-quality studies and nineteen moderate-quality studies. Five main themes, including hypertension, foetal and children’s development, behavioural disorders, respiratory outcomes, and other health outcomes. Majority of studies showed positive link between prenatal ETS exposure and increase risk of preterm birth, and moderately, foetal growth restriction. Few studies explored other potential adverse outcome of ETS, including hypertension, respiratory morbidity, lung function and asthma in their children. Conclusion: The current available evidence on prenatal ETS exposure in Chinese children has unveiled a wide range of health outcomes, including preterm birth, foetal development, behavioural disorders and much more. However, Chinese studies in this area are still lacking and a gap still exists in relation to the strength of association between prenatal ETS exposure and some health risks. Efficient anti-smoking policies and smoking cessation programs should be developed to promote maternal and child health. Further research is also needed to provide better evidence in this field.

Graphene hybrid-filler polymer composites have emerged as prominent materials that revolutionize heavy industries. This study encapsulates the in-depth analysis of different influential factors such as filler/graphene type, aspect ratios, dispersion methods, filler-matrix compatibility, fiber orientation, synergistic effects, different processing techniques, and post-curing conditions that affect the processing, properties and determine the resultant applications of graphene hybrid polymer composites. Additionally, it discusses the substantial role of graphene collaboration with other fillers such as carbon nanotubes, silica, nano-clays and metal oxides to produce functionalized hybrid polymer composites with synergistically enhanced tailored properties to offer solutions for heavy industries like aerospace, automotive, electronics, and energy harvesting. The review concludes with some suggestions and outlook on the future of these composite materials by emphasizing the need for continued research to fully optimize their potential.

The DnaA protein has long been considered to play the key role in the initiation of chromosome replication in modern bacteria. Many questions about this role, however, remain unanswered. Here, we raise these questions within a framework based on the dynamics of hyperstructures alias large assemblies of molecules and macromolecules that perform a function. In this dynamics, hyperstructures can (1) emit and receive signals or (2) fuse and separate from one another. We ask whether the DnaA-based initiation hyperstructure acts as a logic gate receiving information from the membrane, the chromosome and metabolism to trigger replication; we try to phrase some of these questions in terms of DNA supercoiling, strand opening, glycolytic enzymes, SeqA, ribonucleotide reductase, the Macromolecular Synthesis operon, post-translational modifications and metabolic pools. Finally, we ask whether, underpinning the regulation of the cell cycle, there is a physico-chemical clock inherited from the first protocells, and whether this clock emits a single signal that triggers both chromosome replication and cell division.

Background and Objectives: Age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As the inflammation and involvement of the immune system are strongly suggested to have a central role to promote the degenerative process and to stimulate the onset of complications, we aimed to analyze the prevalence of serum anti-retinal (ARA) and anti-endothelial cell antibodies (AECA) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably area of geographic atrophy (GA). Materials and Methods: We enrolled 41 patients with dry AMD and 50 sex- and age-matched healthy controls without AMD. The presence of ARA was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECA was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARA were detected 36 (87.8%) AMD patients (titers range from 1:20 to 1:320) and in 16 (39.0%) (titers range from 1:10 to 1:40) of controls (p=0.0000). Twenty of the 41 patients (48.8%) were positive for AECA, while in a control group AECA were present only in 5 sera (10.0%). The titers of AECA in AMD patients ranged from 1:100 to 1:1000 and in the control group the AECA titers were 1:100 (p=0.0001). There were no significant correlations between the presence of AECA and disease activity. Conclusions: This study provides evidence for the possible involvement of an autoimmune process against retina and retinal vessel antigens in the pathogenesis of geographic atrophy associated with dry AMD.

Herbivores have evolved several strategies to cope with plant defences. Some herbivores are able to resist toxic compounds, while others can manipulate host immunity. Previously it was found that spider mites collected from non-solanaceous wild host plants consist mostly of individuals that induce tomato defences, but also at low frequencies of individuals that can suppress these defences. Also, it has been shown that mites collected from non-solanaceous plants can adapt to tomato by evolving traits that allow them to suppress defences. Hence, we wanted to know if this trait is also common among mites naturally occurring on tomatoes. Here, we compared three T. urticae populations sampled from tomato at three field sites, and also an outbred population created from them through controlled crosses. We then assessed their fecundity on wild-type (WT) tomato plants and def-1 mutants impaired in inducible JA-defences. We also assessed the magnitude of JA defences they induce in WT plants to discriminate between resistant types (high induction and high performance) and those that can suppress defences (low induction, high performance). We then aligned these data with data on variation in mitochondrial DNA cytochrome oxidase I (COI) and effector 84 (a suppressor of JA-defences in planta), in order to compare genetic diversity patterns among mite lines that induce or suppress defences. We found that suppression is the dominant phenotype in mite strains collected from field-grown tomatoes and that inducers and suppressors predominantly cluster in distinct effector 84 clades. We speculate that effector allelic diversity may be subject to natural selection when these mites colonize a novel host plant, promoting traits to cope with plant resistance, such as defence suppression, which facilitates adaptation.

The emergence of drug-resistant parasitic nematodes of both humans and livestock calls for development of alternative and cost-effective control strategies. For the economically important ruminant strongylid Haemonchus contortus, Barbervax® remains the only registered vaccine available. Here we compared the microbiome, genome-wide diversity and transcriptome of H. contortus adult male populations that survived vaccination with an experimental vaccine after inoculation in sheep. Our genome-wide SNP analysis revealed 16 putative candidate vaccine evasion genes. However, we did not identify any evidence for changes in microbial community profiling based of 16S rRNA gene sequencing results of vaccine surviving parasite populations. A total of 58 genes were identified as significantly differentially expressed with six being long non-coding (lnc) RNAs and no putative candidate SNP associated genes. The genes highly upregulated in surviving parasites from vaccinated animals were associated with GO terms belonging to predominantly molecular function and a few biological processes that may have facilitated evasion or potentially lessened the effect of the vaccine. These included five targets: astacin (ASTL), carbonate dehydratase (CA2), phospholipase A2 (PLA2), glutamine synthetase (GLUL) and fatty acid-binding protein (FABP3). We searched all five DEG targets against the proteomes of selected Nematoda (Clades III, V, IV, C, I) and Platyhelminthes (Clades Monogenea, Trematoda, Cestoda, Rhabditophora) to determine homologs within the H. contortus NZ_HCO_NP v1.0 genome and identified single-copy orthologous groups (OGs) in selected proteomes. All but one (FABP3) demonstrated high levels of duplication and wide-spread occurrence in closely related Caenorhabditis elegans and Pristionchus pacificus, with complete absence of all five gene targets among other Clade III (Toxocara canis) and V (Ascaris suum, Ascaris lumbricoides and Parascaris univalens) nematodes, further supporting their vital biological functions in nematodes. Phylogenetic analyses inferred the presence of only ASTL and CA2 in almost all Nematoda, platyhelminthes and metazoans examined, with loss of GLULs observed among all outgroup vertebrate species and the presence of FABP3 in only three other species (Schmidtea mediterranea, Fasciola gigantica and F. hepatica). Our tertiary structure predictions and modelling analyses were used to perform in silico searches of all published and commercially available inhibitor molecules or substrate analogues with potential broad-spectrum efficacy against nematodes of human and veterinary importance.

Fungi are rich sources of secondary metabolites of agrochemical, pharmaceutical and food importances, such as mycotoxins, antibiotics and antitumor agents. Secondary metabolites play vital roles in fungal pathogenesis, growth and development, oxidative status modulation, and adaptation/resistance to various environmental stresses. LaeA contains an S-adenosylmethionine binding site and displays methyltransferase activity. The members of velvet proteins include VeA, VelB, VelC, VelD and VosA, for each member with a velvet domain. LaeA and velvet proteins can form multimeric complexes such as VosA-VelB and VelB-VeA-LaeA. They belong to global regulators and are mainly impacted by light. One of their most important functions is to regulate gene expression that are responsible for secondary metabolite biosynthesis. The aim of this mini-review is to represent the newest cognition on the biosynthetic regulation of mycotoxins and other fungal secondary metabolites by LaeA and velvet proteins. In most cases, LaeA and velvet proteins positively regulated production of fungal secondary metabolites. The regulated fungal species mainly belong to the toxigenic fungi from the genera of Alternaria, Aspergillus, Botrytis, Fusarium, Magnaporthe, Monascus, and Penicillium for the production of mycotoxins. We can control secondary metabolite production to inhibit the production of harmful mycotoxins while promoting the production of useful metabolites by global regulation of LaeA and velvet proteins in fungi. Furthermore, the regulation by LaeA and velvet proteins should be a practical strategy in activating silent biosynthetic gene clusters (BGCs) in fungi to obtain previously undiscovered metabolites.

Type I (IFN-α/β) and Type III (IFN-λ) interferon-inducible myxovirus resistance (Mx) proteins have long been recognized to inhibit a broad spectrum of RNA- and DNA-containing viruses (1-5). Mx proteins are dynamin-family GTPases of size 60-70 kDa (1-3) with different subcellular localization and antiviral activities. In the last 5 years there has been a paradigm shift in our understanding of the structures formed by human and murine Mx proteins in the cytoplasm and nucleus. We now recognize that the major human MxA protein forms structures in the cytoplasm and the major murine Mx1 forms structure in the nucleus which comprise liquid-liquid phase separated (LLPS) biomolecular condensates [membraneless organelles (MLOs)] with a gel-like internal consistency. The second human Mx protein, MxB, which had been previously observed to associate with the cytoplasmic face of nuclear pores, was also recently confirmed to represent cytoplasmic biomolecular condensates. Our overall focus now is to understand the formation, dynamics and antiviral function of biomolecular condensates of different Mx proteins in the cytoplasm and nucleus in cells of different species. We highlight the metastability and rapidly reversible hypotonicity sensing properties of MxA condensates in human cells, especially as applicable to environmental stress inflicted on the oral mucosa.

Histone changes that are adjustable and transmitted without altering the DNA sequence are part of epigenetic control. In many disorders, most famously malignancy, abnormal genetic information is seen as a result of mismanagement of typical epigenetic mechanisms. A paradigm change in the diagnosis and treatment of cancer has been brought about by recent discoveries about the processes of epigenetic modifications, chromatin remodeling, and noncoding RNAs implicated in the changed expression patterns of tumor cells. There is a significant increase in the search for drugs that could alter the epigenetic environment altered by tumor cells and benefit from their therapeutic potential. Phytochemicals with a high concentration of naturally produced phenol molecules known as flavonoids can regulate genomic processes. Understanding the precise epigenetic alterations brought on by flavonoid-mediated mechanisms is necessary to develop combination therapy techniques and genomic therapies for cancer. This article aims to thoroughly examine the epigenetic modifications of flavonoids, including their anticancer properties.

Neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain-Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of ZIKV Asian lineage in South Pacific. Here, we hypothesize that ZIKV-associated GBS relates to a molecular mimicry between viral envelope E (E) protein and neural proteins involved in GBS. Analysis of ZIKV epidemic strains showed that glycan loop (GL) region of the E protein includes an IVNDT motif which is conserved in voltage-dependent L-type calcium channel subunit alpha-1C (Cav1.2) and Heat Shock 70 kDa protein 12A (HSP70 12A). Both VSCC-alpha 1C and HSP70 12A belong to protein families which have been associated with neurological autoimmune diseases in central nervous system. The purpose of our in silico analysis is to point out that IVNDT motif of ZIKV E-GL region should be taken in consideration for the development of safe and effective anti-Zika vaccines by precluding the possibility of adverse neurologic events including autoimmune diseases such as GBS.

In this systematic review, the PRISMA method was applied to examine publications from the last two decades that have investigated the noxious gaseous emissions from dairy barns. The aim was to analyse the outcomes from literature studies estimating the quantities of polluting gases produced in dairy barns, with specific focus on ammonia (NH₃) emissions. The review also explores proposed methods to reduce the associated effects through mitigation strategies. Estimation of NH₃ emissions is significantly influenced by the complex interactions among several factors, including animal management practices, such as controlling animal behavioral activities; manure management, like utilising practices for floor manure removal; the type of structure housing the animals, whether it is naturally or mechanically ventilated; and environmental conditions, such as the effects of temperature, wind speed, relative humidity, and ventilation rate on NH₃ release in the barn. These influential components have been considered by researchers, identifying targeted mitigation strategies. Despite growing attention to the issue, gaps in the scientific literature were identified and discussed, particularly regarding the analysis of mitigation strategies and their long-term impacts (i.e., environmental, economic and productivity-wise).

Ferritin is an indirect marker for total body iron stores. Comparison of the ferritin concentrations in the meconium with the concentrations of proteins regulating iron metabolism could aid better understanding of principles behind the adjustment between the fetal iron pool and newborn body size. Ferritin, transferrin, haptoglobin, ceruloplasmin, lactoferrin, myeloperoxidase, neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin concentrations were measured by ELISA in meconium samples from 122 neonates. The neonates were classified according to the meconium ferritin tertiles and the values were collated with the meconium concentrations of other proteins and newborn body weight and length measurements. Increasing ferritin concentrations in meconium in consecutive tertiles (p < 0.05) were parallel to increased NGAL concentrations (p < 0.05). The interrelationships between the meconium concentrations of transferrin, haptoglobin and NGAL as well as between myeloperoxidase, calprotectin and lactoferrin are maintained in all subsequent tertiles of ferritin concentrations, (p < 0.05). In contrast to ferritin, increasing meconium NGAL concentrations in consecutive tertiles were linked to increased concentrations of transferrin, haptoglobin, lactoferrin and myeloperoxidase (p < 0.05) and of calprotectin, ferritin and ceruloplasmin (p < 0.1). Meconium ceruloplasmin concentrations correlate exclusively with neutrophil granule proteins, i.e. myeloperoxidase, NGAL, lactoferrin and calprotectin (p < 0.05). Meconium ferritin concentrations negatively correlates with birth weight (r= -0.20) and length (r= -0.31) of neonates, whereas NGAL concentrations just with birth length (r= -0.26). The remaining proteins did not show such relationships with the size of the newborn. High meconium concentrations of both ferritin and NGAL may specifically characterize neonates of smaller size. High meconium concentrations of both ferritin and NGAL may specifically characterize neonates with lower body measurements. Correlations between meconium transferrin, haptoglobin and NGAL may confirm the interrelationships of these proteins for proper iron control and transport in the intrauterine environment. Meconium ceruloplasmin concentrations may reflect the control of neutrophil activity in utero.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that these ER-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including total 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the PERK-UPR associated genes: p-eIF2, BCL-2, PERK, ATF4, BAX were investigated by Real-Time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression of PERK, BCL-2, p-eIF2, ATF4, BAX was found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056 and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors, may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

Abstract: Background: Exposure to ETS (Environmental Tobacco Smoke) is one of the most toxic environmental exposures. Objective: To investigate the impact of ETS on physiological, biochemical, psychological indicators, on the urine antioxidant capacity (AC) and oxidative damage to lipids in a pilot sample of healthy pregnant women. Methods: The exposure to ETS was investigated by a validated questionnaire, urine cotinine and the marker of oxidative damage to lipids - 8-isoprostane concentrations using an ELISA kit. Urine AC was determined by the spectrophotometric TEAC method. From the sample of pregnant women (n=319, average age 30.84 ± 5.09 years) in 80 the levels of cotinine and oxidative stress markers were analyzed. Results: From our sample, 5 % individuals (7.4 % objectified by cotinine) were current smokers and 25 % reported passive smoking in the household (18.8 % objectified by cotinine). The Kappa was 0.78 for smokers and 0.22 for ETS exposed non-smokers. Smokers as well as non-smokers had significantly higher (p<0.05) urine AC than ETS exposed non-smokers. Non-smokers had significantly lower levels of 8-isoprostane than smokers (p<0.01) and ETS-exposed non-smokers (p<0.05). Correlations between urine levels of cotinine and AC were positive in ETS exposed non-smokers. Conclusion: The harmful effect of active and passive smoking on oxidative stress parameters has been indicated.

The study was done to determine the effect of supplementing different forms of L-methionine (L-Met) and acetate on protein synthesis in immortalized bovine mammary epithelial cell line (MAC-T Cell): Control, L-Met, conjugated L-Met and acetate (CMA), and non-conjugated L-Met and Acetate (NMA). Protein synthesis mechanism was determined by omics method. NMA group had the highest protein content in the media and β-casein mRNA expression levels (P < 0.05). The number of upregulated and downregulated proteins observed were 77 and 62 in CMA group and 50 and 81 in NMA group from 448 proteins, respectively (P < 0.05). NMA and CMA treatments stimulated pathways related to protein and energy metabolism (P < 0.05). Metabolomic analysis also revealed CMA and NMA treatments resulted in increases of several metabolites (P < 0.05). In conclusion, NMA treatment increased protein concentration and expression level of β-casein mRNA in MAC-T cells compared to CMA.

An opinion dependent cross sectional survey was conducted among charland peoples of Noakhali, Bangladesh with a view to identify the factors that affect green economy. Nijhumdwip Island and Tamaruddi union are highly affected by cyclone and soil salinity. Unpredictable rainfall is the most acute in Nijhumdwip. Lack of information the main problem in Nijhumdwip Island. Farmers are found less interest in integrated farming and crop diversification. Few farmers from Sonadia Union are involved in homestead gardening. Regression analysis have shown a negative relationship (p<0.001) between education of stockholders and decrease of crop production. On the other hand education level of stockholders is to be found positively (p<0.05) varied with decrease of food insecurity. So it can be said that educated farmers are more adaptive against climate change.

The aim of the study was to analyze the in ovo injection of chemically and biologically synthesized silver nano-particles (Ag NPs) using Brassica oleracea L. var capitate f. Rubra, (BOL) conjugation with L-Arginine (L-Arg) on the immune, muscle growth, survivability and hatchability of the broiler chickens. L-Arg (100 μg) with 1000 µg (BOL-Ag NPs) and L-Arg (100 μg) with 100 µg (C-Ag NPs) were injected into fertile eggs at 8, 14 and 18 of incubation. Survival and hatched chicks were calculated. Survivability and hatchability were unaffected by the injected dose of L-Arg (100 μg) with 1000 µg (BOL-Ag NPs) and L-Arg (100 μg) with 100 µg (C-Ag NPs) but it significantly improved when the eggs were injected on day 14 of incubation compared with those injected on days 8 or 18. Moreover, the protein expression of muscle development markers such as myogenin and myoD were significantly up-related in 14 d incubation whereas the heat shock proteins (HSPs) such as HSP-60 and HSP-70 were significantly up-regulated in 18 d incubation. In addition, the in ovo injection on 18 d significantly increased the serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) as well the immunoglobulin (IgM) levels were increased in 14-day incubation period in serum at the same concentration. Collectively, these results indicate that injecting L-Arg (100 μg) with 1000 µg of BOL-Ag NPs or L-Arg (100 μg) with 100 µg of C-Ag NPs to eggs at day 14 after incubation could improve their hatchability, survival rate, and muscle growth marker.

Being a chilling-sensitive staple crop, rice (Oryza sativa L.) is vulnerable to climate change. The competence of rice to withstand chilling stress should, therefore, be enhanced through technological tools. The present study employed chemical intervention like application of sodium nitroprusside (SNP) as nitric oxide (NO) donor and elucidated the underlying molecular mechanisms of NO-mediated chilling tolerance in rice. At germination stage, germination indicators were interrupted by chilling stress (5.0 ± 1.0°C for 8 h day‒1), while pretreatment with 100 μM SNP markedly improved the indicators. At seedling stage (14-day-old), chilling stress caused stunted growth with visible toxicity along with alteration of biochemical markers, for example, increase in oxidative stress markers (superoxide, hydrogen peroxide, and malondialdehyde) and osmolytes (total soluble sugar; proline and soluble protein content, SPC), and decrease in chlorophyll (Chl), relative water content (RWC), and antioxidants. However, NO application attenuated toxicity symptoms with improving growth performance which might be attributed to enhanced activities of antioxidants, mineral contents, Chl, RWC and SPC. Furthermore, principal component analysis indicated that water imbalance and increased oxidative damage were the main contributors to chilling injury, whereas NO-mediated mineral homeostasis and antioxidant defense were the critical determinants for chilling tolerance in rice. Collectively, our findings revealed that NO protects against chilling stress through valorizing cellular defense mechanisms, suggesting that exogenous application of NO could be a potential tool to evolve cold tolerance as well as climate resilience in rice.

Proteins possess complex three-dimensional structures, and these structures are stable only within specific ranges of temperature which mostly correspond to the temperature ranges of the host organisms. However, few exceptional proteins, called heat-stable proteins, are stable at temperatures that are substantially higher than those tolerated by the host organisms themselves. Most of the heat-stable proteins possess heat stability to perform their functions at high temperatures, but some of them are intrinsically heat-stable due to their structure. Heat-stable proteins are usually divided into three or four groups depending upon the intricacies of their structures and thermal behaviors. Their peculiar property, i.e. heat-stability, makes them very valuable in applications such as polymerase chain reaction, industrial processes requiring high temperature, and protein engineering. Heat-stability also makes it feasible to purify such proteins, from the rest of the heat-labile proteins, using a simple heat-treatment method. Moreover, heat treatment can be used as a combined cell-lysis and protein purification step which, as compared to conventional methods, can result in a higher yield of heat-stable proteins. Furthermore, some special heat-stable proteins, i.e. intrinsically disordered proteins (which include the proteins involved in important neurodegenerative diseases), need heat-treatment step, in some cases, as the only way for their successful purification and study. Hence, this paper provides a first-ever comprehensive review of all major aspects of heat-stable proteins, i.e., their structure, evolution, classification, significance, and heat-treatment mediated purification.

The Zika virus (ZIKV) is a mosquito-borne Flavivirus and can be transmitted through an infected mosquito bite or through human-to-human interaction by sexual activity, blood transfusion, breastfeeding or perinatal exposure. After the 2015-2016 outbreak in Brazil, a strong link between ZIKV infection and microcephaly emerged. ZIKV specifically targets human neural progenitor cells, suggesting that proteins encoded by ZIKV bind and inactivate host cell proteins leading to microcephaly. Here, we present a systematic annotation of interactions between human proteins and the seven non-structural ZIKV proteins corresponding to a Brazilian isolate. The interaction network was generated by combining tandem-affinity purification followed by mass spectrometry with yeast two-hybrid screens. We identified 150 human proteins, involved in distinct biological processes, as interactors to ZIKV non-structural proteins. Our interacting network is composed of proteins that have been previously associated with microcephaly in human genetic disorders and/or animal models. This study builds on previously published interacting networks of ZIKV and genes related to autosomal recessive primary microcephaly to generate a catalog of human cellular targets of ZIKV proteins implicated in processes related to microcephaly in humans. Collectively, this data can be used as a resource for future characterization of ZIKV infection biology and help create a basis for the discovery of drugs which may disrupt the interaction and reduce the health damage to the fetus.

Survival of Medulloblastoma (MB) depends on various factors, including the gene expression profiles of MB tumor tissues. In this study, we identified 967 MB survival related genes (SRBs) using the gene expression dataset of Cavalli et al. (2017) and the Cox proportional hazards regression model. Notably, the SRGs were over-represented on chromosomes 6 and 17, known for the abnormalities monosomy 6 and isochromosome 17 in MB. The most significant SRG was HMGA1 (high mobility group AT-hook 1), which is a known oncogene and a histone H1 competitor. High expression of HMGA1 was associated with worse survival, primarily in the Group 3γ subtype. The high expression of HMGA1 was unrelated to any known somatic copy number alteration. Most SRGs on chromosome 17p were associated with low expression in Group 4β, the MB subtype with 93% deletion of 17p and 98% copy gain of 17q. Pathway analysis showed that both chromosomes 6 and 17 included SRGs related to telomere maintenance and provide a rationale for testing telomerase inhibitors in Group 3 MBs. We conclude that HMGA1, along with other SRGs on chromosome 6 and 17 warrant further investigation as potential therapeutic targets in selected subgroups or subtypes of MB.

Health-Related Quality of Life (HRQoL) encompasses the comprehensive evaluation of an indi-vidual's health and well-being across multiple dimensions. Mindfulness, recognized as a scientifi-cally supported strategy for anxiety management, plays a role in enhancing both physical and mental health. The Gut-Brain Axis (GBA) serves as the bidirectional communication link between the gastrointestinal system and the central nervous system. This study aims to explore the associa-tion between Mindfulness and factors influencing the GBA in both healthy individuals and those with Inflammatory Bowel Diseases (IBD). A cross-sectional investigation involved 338 adults, in-cluding 50 IBD patients, utilizing validated Greek scales for Mindfulness (MAAS-15), Mediterra-nean Diet (14-MEDAS), and HRQoL (EQ-5D-5L). The questionnaire gathered demographic, an-thropometric, and lifestyle data. Among healthy participants, EQ-5D-5L showed a moderate cor-relation with the MAAS-15 scale (r=0.389, p

Introduction: Subtalar Arthroereisis (STA) is a surgical intervention for pediatric flexible flatfoot (PFF), primarily targeting hindfoot alignment by limiting excessive subtalar eversion. However, its effects on forefoot parameters remain underexplored. This study aims to investigate radiological changes following STA in pediatric patients. Materials and Methods: A retrospective analysis was conducted on consecutive patients treated with STA for PFF. First ray-related angles, including Hallux Valgus Angle (HVA) and Inter-Metatarsal Angle (IMA), alongside hindfoot radiological parameters such as Meary, Calcaneal Pitch, and Costa Bartani angles, were assessed. Subgroup analysis by gender was performed, and correlations between demographic and pre-operative radiological parameters were examined. Results: Forty-one patients (81 feet) with a mean age of 11.6 years were included, with a mean follow-up duration of 6.4 months. No significant differences were observed in first ray-related an-gles pre- and post-operatively, with mean IMA changing from 7.97° to 7.18° and mean HV angles from 9.51° to 8.66°. Noteworthy improvements were seen in flat foot angles, including Meary, Calcaneal Pitch, and Costa Bartani angles, postoperatively. Age subgroup analysis revealed similar trends in IMA and HVA changes between Group A (operated before peak growth) and Group B (operated later). Higher preoperative angles tended to improve, while lower preoperative IMA and HVA tended to worsen postoperatively, all remaining within normal ranges. Conclusion: STA showed positive radiological outcomes for PFF treatment, while negligible changes in first ray-related angles were observed. Age subgroup analysis indicated similar trends regardless of operation timing. Higher preoperative angles tended to improve, while lower preoperative angles tended to worsen postoperatively, despite all falling within non-pathological ranges. Further re-search is warranted to confirm this correlation.

Obesity and chronic inflammation are well-known risk factors for cancer. Interleukin-33 (IL-33) functions in inflammatory diseases, particularly those related to obesity and cancer. However, the correlation and molecular mechanisms linking IL-33, obesity, and cancer remain unclear. IL-33 is a nuclear cytokine released as an alarm signal when cells are damaged or stressed. It is expressed in epithelial, endothelial, and fibroblast-like cells during normal conditions and in-flammation. When IL-33 is present, immune cells expressing the IL-1RL1/ST2 receptor are alerted in response to tissue damage or cell injury. Research on IL-33 and its correlation with obesity has revealed improvements in inflammatory and metabolic changes associated with obesity. IL-33 can have both pro-tumorigenic and antitumorigenic effects, depending on the cellular content, in-flammatory environment, expression levels, and bioactivity of IL-33. This review will discuss the various functions of IL-33 in obesity-driven inflammation and cancers and how they intersect.

The purpose of this study is to examine the match-related performance (scores and penalties) of the athletes in the Junior EJC (European Judo Championship) and U23 EJC categories before and immediately after the Covid-19 quarantine, according to gender and weight category groups. Our sample was based on the junior and U23, male and females, 2019-2020 Junior European Judo Championships and 2019-2020 U23 European Judo Championships. A total of 1431 matches in these tournaments were analyzed: male (n=812) and female (n=619). The main findings of this study showed that most matches in both the male and female categories resulted in ippon (2019-2020 average: 64,35% for Junior male, 70,55% for U23 male and 69,3% for Junior female, 64,4% for U23 female). No significant differences (p &gt; 0.05) were observed between gender and age groups concerning the match scores. In the formation phase of the technique, considerations of high- and low-intensity actions, and analysis of the speed of athletes during matches in official competitions can help to better understand the dynamics of the variability of movements in judo matches. In addition, suggestions are presented to be applied to athletes in different age categories who are on the way to become Olympic athletes.

The continues evolution of coronaviruses has gained considerable attention prior to the outbreak of COVID 19. Although, COVID-19 is currently not recognized as a global pandemic, the virus's ability to evolve and cause disease outbreaks in both humans and animals necessitates ongoing research into its genetic and structural characteristics. Therefore, understanding the molecular origin, rapid evolution, as were as the immunogenicity of coronaviruses is a critical step towards preparing for and preventing future outbreaks. This study aimed to uncover the genetic diversity and evolutionary relationships among the main viral proteins of SARS-CoV-2 and other related coronaviruses. Amino acid sequences of structural viral proteins spike glycoprotein, nucleocapsid protein, membrane protein, and envelope protein were retrieved from the NCBI database for SARS-CoV-2 and 13 other coronaviruses. Here, we identified that SARS-CoV-2 is closely related to BatCoV RaTG13 and Pangolin-CoV, suggesting their potential role in the emergence of the virus. Additionally, we predicted novel epitopes, glycosylation sites, and cleavage sites, identifying three novel glycosylation sites (NATR, NXSN, and NGTK) and six new CTL epitopes (XSNQVAVLY, NSFTRGVYY, NATRFASVY, STQDLFLPF, NSASFSTFK, and ASFSTFKCY). Our comparative analysis revealed that BatCoV RaTG13 has the closest cleavage site to SARS-CoV-2, with significant similarities also observed with Pangolin-CoV. The study highlighted the unique features of SARS-CoV-2, including its furin cleavage site, which may account for its high infectivity during the pandemic. These findings contribute to the understanding of SARS-CoV-2 evolution and its relationship with other coronaviruses, providing critical insights for the development of broad-spectrum vaccines and antiviral therapies.

The BET family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises Brd2, Brd3, Brd4, and Brdt, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-Myc. These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. This review presents an overview of the basic roles of BET proteins and highlights the pathological functions of BET and the recent developments in cancer therapy targeting BET proteins in animal models.

D-dimer testing in combination with clinical assessment is commonly used to diagnose suspected DVT and pulmonary embolism. However, as D-dimer levels are physiologically higher in elderly patients, this test loses clinical specificity in the setting of geriatric patients. The aim of our study was to investigate the changes in D-dimer levels with age and the specificity of the D-dimer test in the diagnosis of pulmonary embolism. 1617 elderly patients consecutively admitted to the Geriatric Emergency Care Department of the INRCA-IRCCS hospital between January 2013 and February 2014 and for whom D-dimer results were available were included. The D-dimer immunoturbidimetric assay was performed on a cs-2100i Sysmex Siemens using a conventional cut-off level of 500 µg/L. The median D-dimer level was 1200 [550-2990] µg/L FEU, and the percentage of patients with D-dimer levels below the conventional cut-off was only 22.1%. As expected, there was a significant age-related increase in D-dimer, even when sex was considered, and a significant decrease in the specificity of D-dimer assay with age. The most established use of D-dimer testing is in the diagnosis of deep vein thrombosis or pulmonary embolism. Our study confirms the need for an age-adjusted cut-off for D-dimer testing in geriatric patients.

Background: Critical states present scale-free dynamics, optimizing neuronal complexity. We explored electroencephalogram (EEG) criticality in amnesic Mild Cognitive Impairment (aMCI) patients with clinical improvement in working memory, verbal memory, verbal fluency and overall executive functions after the completion of a 6-month prospective memory training. (2) Methods: We compared “before” and “after” stationary resting-state EEG records of right-handed MCI patients (n = 17; 11 females), using the method of critical fluctuations and Haar wavelet analysis. (3) Results: Significant criticality enhancement was present in frontotemporal electrodes [mean dif: 0.10; Z = 7, p = .019] and isolated electrodes T6 [mean dif: 0.204; t (10) = - 2.3, p = .044] and F4 [mean dif: 0.0194; t (10) = - 2.82; p = .018]. (4) Conclusions: EEG criticality agreed with clinical improvement, consisting a possible monitoring biomarker in MCI and Alzheimer’s disease. Further evaluation is needed in patients under cognitive training or even drug-modifying therapies.

Resistance of tumor cells to anticancer drugs is a major obstacle in tumor therapy. In this study, we investigated the mechanism of cordycepin-mediated resensitization to cisplatin inT24R2, a derived T24 cell line. Treatment with cordycepin or cisplatin (2 g/ml) alone could not induce cell death of T24R2, but combination treatment of these drugs significantly induced apoptosis of the cells through mitochondrial pathway including depolarization of mitochondrial membrane, decrease of anti-apoptotic proteins, Bcl-2, Bcl-xL, and Mcl-1, and increase of pro-apoptotic proteins, Bak and Bax. . High expression of MDR1 was the cause of cisplatin resistance in T24R2, and cordycepin significantly reduced MDR1 expression through inhibition of MDR1 promoter activity. MDR1 promoter activity was dependent on a transcription factor, Ets-1, in T24R2 cells. Although there is a correlation between MDR1 and Ets-1 expression in bladder cancer patients, active Ets-1, Thr-38 phosphorylated form (pThr-38), was critical to induce MDR1 expression. Cordycepin decreased pThr-38 Ets-1 level through inhibition of AKT, which reduced MDR1 transcription and induced the resensitization of T24R2 to cisplatin. The results suggest that cordycepin effectively resensitizes cisplatin-resistant bladder cancer cells to cisplatin, thus serving as a potential strategy for treatment of anti-cancer drug resistant patients.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, wings, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects and all other arthropods. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. As a means of renaming this protein family, this review article discusses the latest findings (“CSP” is attached to the tail of bigger intracellular proteins) and attempts to compel all the data. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins) and use at least for abbreviations for distinctive animal proteins the common peptide 5-letter code, such as “Bommo-4CSPs”.

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

The Rose grain aphid, a notable agricultural pest, releases saliva while feeding. Yet, there is a need for a comprehensive understanding of the specific identity and role of secretory proteins released during probing and feeding. Therefore, a combined transcriptomic and proteomic approach was employed to identify putative secretory proteins. The transcriptomic sequencing result led to the assembly of 18030 unigenes out of 31344 transcripts. Among these, 705 potential secretory proteins were predicted and functionally annotated against publicly accessible protein databases. Notably, a substantial proportion of secretory genes (71.5%, 69.08%, and 60.85%) were predicted to encode known proteins in Nr, Pfam, and Swiss-Prot databases, respectively. Conversely, 27.37% and 0.99% of gene transcripts were predicted to encode known proteins with unspecified functions in the Nr and Swiss-Prot databases, respectively. Meanwhile, the proteomic analysis result discovered, 30 salivary proteins. Interestingly, most salivary proteins (53.3% proteins) showed close similarity to A. craccivora, while 36.67% to A. pisum and A. glycines. However, to verify the expression of these secretory genes and characterize the biological function of salivary proteins further intervention should be geared towards gene expression and functional analysis.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports the role of the immune system, mainly played by alveolar macrophages (AMs), as key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore theirinvolvment in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine expression of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insight for diagnosis or pharmacological treatment.

Microglial cells are brain macrophages that support and protect the central nervous system enviroment. Aging induces alterations in microglial polarization, resulting in a shift towards a neurotoxic phenotype characterized by increased expression of pro-inflammatory markers. Dysregulation of microglial cells regulatory pathways and interactions with neurons contribute to chronic activation and neurodegeneration. A better understanding the involvement of microglia in neurodegenerative diseases like Alzheimer's and Parkinson's, is a critical topic to studying the role of inflammatory responses in disease progression. Furthermore, the metabolic changes in aged microglia, including downregulation of oxidative phosphorylation are discussed in this review. Understanding these mechanisms is crucial for developing better preventive and therapeutic strategies.

Abstract: A. baumannii exhibits resilience in harsh environments and progressively develops resistance to diverse antibacterial agents over time. This adaptability poses a significant challenge in treating an infection caused by this bacterium within healthcare settings. The presence of peptidoglycan, a crucial precursor for cell wall synthesis, contributes to this challenge. Peptidoglycan serves not only as a structural support in bacterial cells but also provides protection against adverse environmental conditions. The synthesis of the peptidoglycan layer involves a group of substrates such as N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), within a three-partitioned process occurring in the membrane, periplasmic space, and cytoplasm of each bacterium. Initiated in the cytoplasm and extending to the inner cell membrane, this synthesis starts with the production of nucleotide precursors. The first step involves the synthesis of UDP-GlcNAc, orchestrated by Glm (GlmS, GlmM, and GlmU) enzymes using fructose-6-phosphate. Subsequently, enzymes from the Mur family, namely MurB, MurA, MurD, MurC, MurI, MurF, and MurE, synthesize UDP-N-acetylmuramyl-pentapeptide (UDP-Mpp) from UDP-GlcNAc. Concurrently, on the cytosolic side, the production of membrane-surrounded undecaprenyl phosphate occurs, involving membrane-side proteins MraY and MurG in the biosynthesis of peptidoglycan. This review emphasizes updated information on Mur family proteins, encompassing physicochemical properties, nature of binding site, number and type of binding site residues, functional domain details, three-dimensional structural aspects, and their functions within bacterial cells. Special attention is directed towards their enzymatic role in peptidoglycan biosynthesis due to the limited availability of precursors in the market. Additionally, the review provides a comprehensive summary of existing inhibitors and ongoing efforts in identifying new targeted inhibitors, recognizing these enzymes as potential candidates for antibacterial drug design and discovery.

Gestational Diabetes Mellitus (GDM) is related with adverse outcomes for both the mother and the offspring. Immune and senescence play a crucial role in GDM progression. This study aims to explore the diagnostic significance of immune-related senescence (IRS) genes in GDM. We used weighted gene co-expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) to compute the immune score and aging score in control and GDM samples. Machine learning identified core IRS genes. Then we performed unsupervised cluster analysis in GDM patients to explore immune infiltration. Finally, we validated the core genes in clinical samples. We used the intersection of MEblack module from WGCNA and differentially expressed genes (DEGs) to obtain the potential genes. Next, a univariate logistic regression model including 23 potential genes were constructed, and these genes were filtered by least absolute shrinkage and selection operator (LASSO) algorithm. There were 5 potential genes (COX17, RRAS2, RRAGC, CECR1, and TACC2), which defined as biomarkers, remained eventually, and the efficacy of these biomarkers was evaluated by nomogram. Finally, the results from both qRT-PCR and western blot analyses demonstrated CECR1 was down-regulated, while TACC2 was up-regulated in GDM placental tissue. Our study identified CECR1 and TACC2 as diagnostic biomarkers for GDM associating with immune and senescence, providing a new perspective on GDM progression.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

Long COVID (Post-Acute Sequelae of COVID-19, PASC) is a consequence of infection by SARS-CoV-2 that continues to disrupt the well-being of millions of affected individuals for many months beyond their first infection. While the exact mechanisms underlying PASC remain to be defined, hypotheses regarding the pathogenesis of Long COVID are varied and include (but are not limited to) dysregulated local or systemic inflammatory responses, autoimmune mechanisms, viral-induced hormonal imbalances and long-term persistence of virus and/or fragments of viral RNA or proteins. This review article is based on a comprehensive review of the wide range of symptoms most often observed in long COVID and an attempt to integrate that information into a plausible hypothesis for the pathogenesis of PASC. In particular, it is proposed that longterm dysregulation of the gut in response to viral persistence could lead to the myriad of symptoms observed in PASC.

Fish kills in Southeast Asia are frequently associated with harmful algal blooms (HABs) and cause significant ecological and economic impacts. This paper serves as a review of fish kill events with focus on those related to HABs within the region. It examines the causative algal species, known mechanisms of fish mortality, and socio-economic consequences. Fish kills have been reported across multiple countries within Southeast Asia, with notable hotspots in the Philippines, Malaysia, Singapore, Indonesia, and Thailand. The common harmful microalgal species span a diverse group including dinoflagellates (Karenia spp., Karlodinium spp., Margalefidinium polykrikoides, Noctiluca scintillans), raphidophytes (Chattonella spp.), diatoms (Skeletonema spp. and Chaetoceros spp.), and cyanobacteria (Trichodesmium spp.). These microalgae lead to fish kills through mechanisms such as hypoxia, physical gill damage, and ichthyotoxin production. Freshwater fish kills linked to HABs have also been documented for the Philippines, but there is no or limited information for the region. Our review highlights the widespread and recurring nature of fish kills, their impact on fisheries and aquaculture, and challenges in managing and mitigating their effects. There are efforts at enhancing management and mitigation using clay and early-warning systems. However, it is essential to further improve monitoring efforts, the development and deployment of early-warning systems, and viable and holistic mitigation strategies to protect the region’s aquatic resources and dependent communities, especially as aquaculture and coastal development are increasing concurrent with a changing climate that can exacerbate the risks of fish kills and HABs in Southeast Asia.

Synucleins are a family of small, soluble proteins mainly expressed in neural tissue and in certain tumors. Since their discovery, tens of thousands of scientific reports have been published about this family of proteins as they are associated to severe human diseases. Although the physiological function of these proteins still elusive, their relation with neurodegeneration and cancer was clearly described over the years. In this review, we summarize data connecting synucleins and cancer, going from the structural description of these molecules, to their involvement in tumor-related processes, and discuss the putative use of this proteins as cancer molecular biomarkers.

Seventy-seven percent of Irish primary school children do not meet recommended physical activity (PA) guidelines [1]. The Daily Mile (TDM) is a primary school initiative designed to increase children’s PA output. This study evaluates TDM’s perceived effect on Irish primary school children’s health-related metrics. A mixed-methods study, comprising two data collection phases, used the RE-AIM framework to evaluate TDM [2]. Phase one involved teachers, principals and classroom assistants (n = 191) from TDM-registered schools completing a questionnaire. Two TDM-registered schools participated in phase two where, (i) interviews were conducted with each principal, (ii) a teacher sub-sample (n = 4) participated in a focus group and (iii) a child sub-sample (n = 14) participated in separate focus groups. TDM was perceived to positively impact markers of children’s health, including their PA behaviour, physical fitness and social wellbeing. Inclement weather (66.5%) and a lack of time (56.5%) were reported as the top-ranked implementation barriers. Moreover, TDM’s repetitive nature often left children feeling disinterested and resulted in some teachers modifying the initiative to maintain engagement levels. Maintaining the long-term implementation of TDM and its health benefits in primary schools may require bespoke amendments to the original format to preserve children’s engagement.

In mammals, Tripartite motif-containing (TRIM) proteins modulate the immune response by coordinating pro-inflammatory related processes such as antiviral restriction, cellular autophagy and inflammasome activation. In fish, TRIM proteins have been reported mainly in cyprinids (e.g., carp, zebrafish) and salmonids (rainbow trout). However, their molecular mechanisms and functions are still being described these animals. Our study focused on characterizing novel TRIM proteins involved in the innate immune response of gill cells from rainbow trout stimulated with LPS or poly(I:C). Also, a fish trial was performed to detect TRIM proteins of rainbow trout after a challenge with Flavobacterium psychrophilum, a salmonid bacterial pathogen. At in vitro level, the results showed that, among several TRIM proteins, OmTRIM25 triggered an LPS-induced expression of pro-inflammatory cytokines (TNF-α2 and IL-1β), suggesting a potential local modulatory function. Moreover, in the fish trial, while OmTRIM25 and finTRIM2 were up-regulated in the gills two days post infection (dpi), IL-1β and TNF-α2 reached their peaks of expression at four- and six-dpi. Finally, after delving into the function of OmTRIM25 by RNA interference (RNAi) gene-silencing, we propose that TRIM proteins such as OmTRIM25 are needed to induce the pro-inflammatory response in the gills of rainbow trout, which confirms their immunomodulatory function.

PDEF is expressed in luminal epithelial cells of the prostate gland and associates with luminal phenotype. Hippo pathway regulates cell growth/proliferation, cellular homeostasis, and organ development by modulating phosphorylation of its downstream effectors. In previous studies, we observed decreased levels of PDEF during prostate cancer progression. In the present studies, we evaluated the effects of PDEF on total and phospho (Ser-127)YAP1 protein(a downstream effector of the Hippo pathway) levels in PC3 cells, a line of castrate resistant prostate cancer. We observed that the expression of PDEF in PC3 cells resulted in increased increased phospho(Ser127) -YAP1 protein levels. Our immunofluorescence analysis for YAP1 revealed an increased cytoplasmic/nuclear ratio of YAP1 in PDEF-PC3 cells as compared to VC-PC3 cells, suggesting PDEF may play a critical role in modulating YAP1 phosphorylation, and by extension in the regulation of the Hippo pathway. We also observed a decrease in YAP1 protein levels in prostate cancer tissues as compared to normal prostate tissues. Our analysis of multiple publicly available clinical cohorts revealed a gradual decrease in YAP1 mRNA expression during prostate cancer progression and metastasis. This decrease was similar to the decrease in PDEF levels which we reported earlier. In addition we observed further decreased in PDEF and YAP1 expression in Neuro-Endocrine Prostate Cancer (NEPC), and a direct correlation between PDEF and YAP1 expression. To the best of our knowledge, these results provide the first demonstration of modulation of YAP1 by PDEF in any system and suggest a cross-talk between PDEF and the Hippo pathway.

Background: The aim of this systematic review was to evaluate diagnostic accuracy of molecular-based LTPs serum IgE for the diagnosis of food allergies in patients with suspected allergy to one of the LTPs-containing food. Methods: cohort, prospective or retrospective cross- sectional studies were considered for inclusion in the review. Oral food challenge (both open and double-blind placebo-controlled) was the reference standard for the diagnosis. Pubmed (MEDLINE), Web of Science, Scopus, and ClinicalTrial.org were searched for relevant papers. Risk of bias was assigned by QUADAS-2 tool. Data were reported as sensitivity and specificity. Study protocol was registered in the PROSPERO database (CRD42022321985). Results: Fifteen articles, including 2395 individuals, were included. Sensitivity of Ara h 9 for peanut allergy diagnosis ranged from 6 to 61%; specificity ranged from 57 to 100%. Cor a 8 sensitivity ranged from 11 to 43%, with specificity ranging from 59 to 94%. Conclusions: Ara h9 and Cor a 8 serum IgE may be useful to confirm diagnosis of peanut and hazelnut allergy in symptomatic patients, although diagnostic accuracy is limited by low sensitivity. More investigation on other LTPs and in adult population may be important to define the clinical role of this test in food allergies diagnostics.

Children on farms face high risks of work and non-work-related fatalities, with tractors being a significant contributor. This study examines children's involvement in fatal tractor-related accidents within agriculture in Iceland in 1950-2024, explores adult reflections on childhood tractor-driving experiences, and analyses Members of Parliament´s arguments against setting a minimum age for off-road tractor driving. Data rests on fatal tractor-related accidents using newspaper archives and supplementary sources, narrative interviews with former summer children who stayed at farms in childhood, and parliamentary debates on tractor-related legislation. Over half of the 81 registered accidents involved children, primarily boys, with 75% occurring between 1958 and 1988 when no minimum age for off-road tractor driving existed. Children's fatality incidence rate was more than four times higher than adults. Arguments against minimum age requirements for off-road driving included the need for child labour, children's superior driving skills, and a denial that children were more often victims than adults. Since 1988, no child has died when driving a tractor. A human-centred approach focusing on working conditions, driver capacity, and adherence to safety procedures and legal frameworks is needed to prevent future accidents.

Purpose: This integrated review aims to identify and analyze the multifactorial contributors to the longevity of direct restorations, focusing on tooth-, patient-, and dentist-related factors. Materials and Methods: A literature search was performed using an electronic database, PubMed/Medline, Web of Science, and Scopus, between 1980 and 2024. Titles and abstracts of papers that evaluated aspects categorized into tooth-related, patient-related, and dentist-related factors influencing restoration failure were selected and screened. Full-text assessments were conducted, and the extracted data were compiled, summarized, and synthesized. The reference lists of the collected papers were also screened, and relevant citations were included in this review. Data were gathered from clinical and laboratorial studies, systematic reviews, and meta-analyses to provide a comprehensive understanding of restoration longevity. Results: Among the tooth-related factors, multiple-surface restorations, deep margins, tooth location, and tooth vitality significantly impact restoration survival. Patient-related factors such as medical conditions, risk predictors of caries, age, sex, parafunctional habits, smoking, periodontal health, number of restorations, and socioeconomic status all play crucial roles. Regarding dentist-related factors, the decision-making process, age, experience, and dentist manual dexterity are vital aspects. Furthermore, the technique used, including isolation methods for moisture control, as well as the type of dental practice (large group vs. small practice), notably influenced the restoration survival. Conclusions: The longevity of dental restorations is influenced by a complex interplay of tooth-related, patient-related, and dentist-related factors. Strategies to improve restoration outcomes should consider all these multifactorial contributors. Continuing professional education, diligent patient guidance on the factors that influence restoration survival, careful material selection and restorative technique, and tailored individual treatment are crucial factors to reduce failure rates and improve the lifespan of restorations.

Long COVID, characterized by persistent symptoms lasting from weeks to several months following initial infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), significantly impacts individuals' quality of life and poses a potential long-term burden on global healthcare systems. Clinical manifestations of Long COVID are diverse, affecting multiple systems including respiratory, cardiovascular, neurological, and gastrointestinal. While the precise mechanisms underlying Long COVID remain unclear, emerging evidence suggests involvement of various bodily pathways. This study employs bioinformatics tools to investigate the mechanisms of Long COVID and identify potential drug targets associated with key pathways, including inflammation, cytokines, immune response, coagulation, mitochondrial function, oxidative stress, and autonomic dysfunction. Tools such as the National Center for Biotechnology Information (NCBI) database, PubChem, UniProt, and iGEMDOCK were utilized for pathway analysis and molecular docking. The analysis aimed to identify drug molecules that may interact with target proteins to regulate or inhibit pathway activity, yielding several potential drug candidates for further investigation.

In the intricate dance between viruses and host cells, RNA-binding proteins (RBPs) serve as crucial orchestrators of gene expression and cellular processes. We will delve into the riveting realm of viral hijacking, where viruses deftly exploit host RBPs to manipulate cellular machinery for their replication and pathogenesis. Through a masterstroke of molecular subterfuge, viruses co-opt RBPs involved in various facets of RNA metabolism - from transcription to degradation - to promote viral gene expression and evade host immune defenses. This manipulation leads to global alterations in cellular RNA metabolism, impacting essential host genes vital for immune responses and homeostasis.Unveiling this clandestine alliance between viruses and RBPs is not just a scientific pursuit, but a critical imperative for devising innovative antiviral strategies to disrupt these interactions. By unraveling the intricate interplay between viral proteins and host RBPs throughout the viral life cycle - from entry to assembly - researchers aim to identify vulnerabilities that can be targeted for therapeutic intervention. Strategies such as disrupting viral protein-RBP interactions hold promise for inhibiting viral replication and curbing pathogenesis, offering a beacon of hope in the battle against viral infections.Our manuscript elucidates the indispensable roles played by RBPs in viral replication, translation, and pathogenesis, shedding light on the molecular mechanisms driving viral success. Delving deeper, it explores how viruses intricately entwine with host RBPs, manipulating cellular signaling pathways to create a hospitable environment for viral spread. By dissecting these manipulative tactics, researchers uncover new targets for antiviral therapy, envisioning a future where tailored interventions disrupt viral-host RBP interactions with precision and efficacy.As the narrative unfolds, the therapeutic implications of targeting RBPs or their interactions with viral proteins emerge as a promising frontier in the fight against viral infections. From small molecule inhibitors to RNA-based therapeutics, innovative approaches are on the horizon, offering new avenues for combatting viral diseases. We set the stage for future research, beckoning researchers to delve deeper into the molecular intricacies of viral hijacking of RBPs and charting a course towards novel therapeutic interventions that promise to reshape the landscape of antiviral therapy.\Ultimately, it beckons the scientific community to embark on a voyage of discovery, unraveling the secrets of viral hijacking of RBPs and paving the way for transformative advances in antiviral therapeutics. The stage is set for a new chapter in the battle against viral infections, where knowledge becomes the sword and innovation the shield against the pernicious machinations of viral pathogens.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Computational models of homologous protein groups are essential in sequence bioinformatics. Due to the diversity and rapid evolution of viruses, the grouping of protein sequences from virus genomes is particularly challenging. The low sequence similarities of homologous genes in viruses require specific approaches for sequence- and structure-based clustering. Furthermore, the annotation of virus genomes in public databases is not as consistent and up-to-date as for many cellular genomes. To tackle these problems, we have developed VOGDB, a database of Virus Orthologous Groups. VOGDB is a multi-layer database that progressively groups viral genes into groups connected by increasingly remote homology. The first layer is based on pair-wise sequence similarities, the second layer is based on the sequence profile alignments and the third layer uses predicted protein structures to find the most remote homology. VOGDB groups allow for more sensitive homology searches of novel genes and increase the chance of predicting annotations or inferring phylogeny. VOGDB uses all virus genomes from RefSeq and partially re-annotates them. VOGDB is updated with every RefSeq release. The unique feature of VOGDB is inclusion of both prokaryotic and eukaryotic viruses in the same clustering process which makes it possible to explore old evolutionary relationships of the two groups. VOGDB is freely available at https://vogdb.org under the CC BY 4.0 license.

The fast fashion industry has a significant impact on the environment at every stage of the product life cycle. There is a lack of research in the literature on the impact of fast fashion on the environment through logistics and transport. In this area, the greatest environmental impact is caused by air emissions, which is very important from the point of view of climate change. Therefore, this article deals with the analysis of the carbon footprint resulting from the fast fashion logistics process. The identification and assessment of fast fashion companies' sustainability efforts in the area of transport-related emissions and sustainable transformation strategies was conducted using a case study method for selected brands (H&M Group; Inditex, Shein). The study uses secondary data available in non-financial reports from 2023. After analyzing the data and content in non-financial reports on transport-related emissions, sev-eral important conclusions emerge. As a dominant practice, companies emphasize their reliance on external frameworks and standards, in particular the Global Reporting Initiative and the Task Force on Climate-related Financial Disclosures. Companies prioritize reducing emissions from significant factors, such as production processes. The data disclosed in the reports (scope 1, 2, 3) are not clearly formulated, but they can be used to calculate the level of CO2 emission reduction/increase. The ar-ticle contains recommendations for companies to improve their reporting by including additional indicators expressing the efficiency of transport-related emissions.

Abstract: The emergence of the COVID-19 pandemic has led to the rapid and worldwide devel-opment and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aims to explore the current knowledge on potential endocrine adverse effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pi-tuitary, adrenal, diabetes, and gonadal events will also be reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. A PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar research were performed. Case reports case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines is accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of endocrine disorders linked to COVID-19 vac-cines.

Zn is an essential element for children related to optimal growth, development and nutritional metabolism. We measured Zn bioaccesibility (Zn-BA) levels of foods by Inductively coupled plasma mass spectrometry (ICP-MS) after in vitro digestion-fermentation method from children with gluten related disorders (GRD-CH), obesity (OB-CH) and allergy/intolerance to cow’s milk proteins (AICM-CH). Zn-BA levels in sick children (34.7 ± 28.8, 29.6 ± 30.1 and 26.7 ± 30.4%, respectively) were significantly lower (p &lt; 0.05) than in healthy norm-weight children (HE-CH). For AICM-CH, Zn-BA in animal foods was significantly lower than in plant foods, and in both plant and animal foods from sick and healthy children (p &lt; 0.05). In foods of animal origin in sick and healthy children, Zn-BA in foods heated in liquid media (frying and boiling) was significantly higher than in foods heated by hot air (roasting and grilling). In conclusion, in children the studied diseases diminished the Zn-BA, probably by the alteration of the gut microbiota which could negatively affect their appropriate long-term development. In AICM-CH, the allergy to cow's milk proteins could induce intestinal dysbiosis and inflammatory processes, leading to allergies to other animal food proteins, and to a more pronounced decrease of Zn-BA.

The role of astro- and microglial cells in the pathogenesis of epilepsy is currently under active in-vestigation. It is proposed that the activity of these cells may be regulated by agonists of peroxi-some proliferator-activated nuclear receptors (PPARs). The objective of this study was to investi-gate the effects of the PPAR β/δ agonist GW0742 (Fitorine) on the behavior and gene expression of astro- and microglial proteins involved in the regulation of epileptogenesis in rat brain in a lithi-um-pilocarpine model of temporal lobe epilepsy (TLE). A seven-day administration of GW0742 at a dose of 5 mg/kg/day has been shown to suppress TLE-related behavioral hyperactivity in the Open Field test and to attenuate the TLE-induced increase in gene expression and protein levels of astro- and microglial activation markers Gfap and Aif1 in the dorsal hippocampus and temporal cortex. Furthermore, GW0742 reversed the TLE-related increase in Lcn2 gene expression (a marker of the A1 phenotype of astrocytes) in the temporal cortex, the increase in the ratio of Nos2/Arg1 gene expression (markers of the M1/M2 phenotypes of microglia), and the decrease in Arg1 gene ex-pression in the dorsal hippocampus. The results suggest that GW0742 may mitigate behavioral and biochemical abnormalities in a lithium-pilocarpine model of TLE.

The ovary is the major determinant of female reproductive health. Ovarian functions are mainly related to the primordial follicle pool, which is gradually loss with aging. Ovarian aging and reproductive dysfunctions share oxidative stress as common underlying mechanism. ROS signaling is essential for normal ovarian processes yet can contribute to various ovarian disorders when disrupted. Therefore, balance in the redox system is crucial for proper ovarian functions. In the present study, by focusing on mRNAs and ncRNAs described in the ovary and taking into account only validated ncRNA interactions, we built up an ovarian antioxidant ceRNA network, namely OvAnOx ceRNA, composed of 5 mRNAs (SOD1, SOD2, CAT, PRDX3, GR), 10 miRNAs and 5 lncRNAs (XIST, FGD5-AS1, MALAT1, NEAT1, SNHG1). Our bioinformatic analysis indicated that the components of the OvAnOx ceRNA not only contribute to antioxidant defence, but are also involved in other ovarian functions. Indeed, antioxidant enzymes encoded by mRNA of OvAnOx ceRNA operate within a regulatory network that impacts ovarian reserve, follicle dynamics, and oocyte maturation in normal and pathological conditions. The OvAnOx ceRNA represents a promising tool to unravel the complex dialogue between redox potential and ovarian signalling pathways involved in reproductive health, aging and diseases.

Background/Objectives: Patient positioning during surgery can influence intra- and postoperative complications. Therefore, we assessed the impact of the sitting and park-bench positions on anesthetic parameters and complications in neurosurgical patients. Methods & Patients: For this retrospective study, 314 adults who underwent neurosurgical procedures for posterior fossa pathologies were divided into two groups: sitting (n=231) and park bench (n=83). The following data were collected, monitored, recorded and compared: age, sex, tumor type, surgical approach, cardiovascular and respiratory complications, and postoperative surgical complications. The association of hypotension with position was further investigated through multivariate logistic regression models by adjusting for CO2 decrease, desaturation and documented gas embolism. Results: The average age was significantly lower in the sitting group (55 years, interquartile range (IQR)=43-63; female proportion=59.74%) than in the park-bench group (62 years, IQR=45-74; female proportion=57.83%) (p<0.001). Cerebellopontine angle tumors were detected in 37.23% of the patients who underwent operation in the sitting position and in 7.26% who underwent operation on in the park-bench position (p<0.001). Patients in the sitting position had significantly greater anesthetic complication (91.77% vs. 71.08%, p<0.001), hypotension (61.9% vs. 16.87%),and >2-mmHg CO2 decrease (35.06% vs. 15.66%, p<0.001) incidences. Hypoxemia and death occurred more frequently in the park-bench group (8.43% vs. 1.73% and 6.03% vs. 1.3%, respectively). Conclusions: Compared with the park-bench position, the sitting position was associated with a greater specific anesthetic complication incidence and lower postoperative mortality rate, indicating a need for careful risk‒benefit assessment when selecting each individual patient’s surgical position.

This study investigated interactions between sugar-related dietary patterns (DP), personality traits, cognitive-behavioural, and emotional functioning. The study involved females aged 18-54. Data were collected between the Winter and Spring of 2020/21. The survey was conducted using anonymized questionnaires. The Ten-Item Personality Inventory (TIPI) was used to examine personality traits based on the Big Five Personality Trait Model. Three-Factor Eating Questionnaire (TFEQ) was used to measure eating behaviours: cogni-tive restraint (CR), uncontrolled eating (UE), and emotional eating (EE). The KomPAN question-naire collected the frequency of intake. Dietary patterns (DPs) were derived by principal component analysis (PCA). A logistic regression (OR) was applied to verify the association between the DPs, personality traits, cognitive-behavioural and emotional functioning. Three DPs were identified: sweet-western (SWDP), pro-healthy (PHDP) and dairy (DDP). Women with high conscientiousness were less likely, by 33%, to adhere to the upper tercile of SWDP and 80% more likely to the upper tercile of PHDP. Elevated CR intensity increased by almost 2-fold (OR: 1.93; p

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study is to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts in weight management, body fat, appetite, lipid, and glucose profiles, in an overweight population, for 90 days. As a result, the volunteers presented significant weight loss in absence of diet, which coincided with decreased body fat. Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scan. Cholesterol levels were also significantly decreased. Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal, compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals, in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products, as part of a healthy lifestyle.

Adhesive-invasive E. coli have been suggested to be associated with the development of Crohn's disease (CD). It is assumed that they can provoke the onset of the inflammatory process as a result of the invasion of intestinal epithelial cells, and then, due to survival inside macrophages, stimulate chronic inflammation and the development of granuloma. In previous reports, we have shown that passage of the СD isolate ZvL2 on minimal medium M9 supplemented with sodium propionate (PA) as a carbon source stimulates, and with glucose - inhibits the adherent-invasive properties and the ability to survive in macrophages. This effect was reversible and not observed for the laboratory strain K12 MG1655. We were able to compare the isogenic strain AIEС in two phenotypes - virulent (ZvL2-PA) and non-virulent (ZvL2-GLU). We showed that, unlike ZvL2-GLU, the ZvL2-PA activates the production of ROS and cytokines when interacting with neutrophils. The laboratory strain does not cause a similar effect. Differences in neutrophil NADH-oxidase activation and ζ potential for ZvL2-GLU and ZvL2-PA are associated with changes in the abundance of membrane proteins. Using differential 2D electrophoresis and LC-MS, we identified membrane proteins that may be associated with the activation of the virulence properties of the СD isolate ZvL2.

Background: Oxidative stress has emerged as a key contributor to numerous NCDs (Non Communicable Diseases), including cardiovascular diseases, cancer, and diabetes. This study aims to explore the potential of targeted interventions to mitigate oxidative stress as part of a primary prevention strategy. Methods: The study included 32 healthy participants (11 men, 21 women) aged 45-65 who completed both the initial and follow-up assessments of the Healthy Days Initiative, a community-based wellness program organized by the non-profit Associazione O.R.A. ETS. Through blood analysis, vital sign assessment, lifestyle questionnaires, and individualized recommendations, participants received guidance on improving their health and reducing disease risk. The initiative also offered the opportunity for participants to consume a flavonoid supplement containing quercitrin, rutin and hesperidin, with the goal of reducing oxidative stress. Participants who opted for supplementation were instructed to take 1-2 tablets daily for two weeks. Data collected included demographic information, anthropometric measurements, vital signs, dietary and lifestyle habits, medical history, WHO-5 Well-Being Index scores, and blood parameters. Results: Significant reductions were observed in glucose levels (from 82 to 74.5 mg/dL), reactive oxygen metabolites (d-ROMs) (from 394.5 to 365.5 U.CARR), and systolic blood pressure (from 133 to 122 mmHg) after the two-week flavonoid intervention. Most participants (26/31) reported no side effects, and the majority (30/31) expressed a willingness to continue using a product combination of quercitrin, rutin and hesperidin or a similar product long-term. Conclusions: While limited in scope and duration, the PREVES-FLAVON study contributes valuable insights to the growing body of evidence suggesting that flavonoid supplementation may play a significant role in reducing risk factors associated with NCDs in primary prevention settings. By targeting novel risk factors such as oxidative stress, this intervention holds promise for mitigating the global burden of NCDs and promoting healthy aging.