The CuCrSn alloy is promising as high-strength and high-conductivity Cu alloy due to its relative low smelting requirement, while thus far reports on the CuCrSn alloy is still quite lacked. In this study, the microstructure and properties of Cu-0.20Cr-0.25Sn (wt%) specimens prepared under different rolling and aging combinations were comprehensively characterized, in order to reveal the effects of cold rolling and aging on the CuCrSn alloy. The results show that increasing the aging temperature from 400 ºC to 450 ºC can obviously accelerates the precipitation, and the cold rolling before aging significantly increases the initial microhardness and promotes the precipitation. Whereas, the deformation hardening will be eliminated during the aging process, making the microhardness even decrease monotonically when the aging temperature and the rolling ratio before aging are high. Performing the cold rolling after the aging can maximize the effects of precipitation strengthening and deformation strengthening, and its adverse impact on the conductivity is not serious. A tensile strength of 506.5 MPa and a conductivity of 70.33% IACS were obtained with such a treatment, only the elongation decreases. Different strength-conductivity combinations of the CuCrSn alloy can be achieved through appropriate combinations of the aging and post aging cold rolling conditions.

Genes encoding retinol binding protein 4 (RBP4), follicle stimulating hormone subunit beta (FSHB) and epidermal growth factor (EGF) have been proposed as candidate genes for reproduction traits in pigs. The study presented in this paper aimed to find associations between variants of these genes and reproduction traits in pigs reared in Poland. Investigation included Polish Large White x Polish Landrace (n=288) and Yorkshire (n=195) sows. Individual genotypes were determined by means of PCR-RFLP (single nucleotide polymorphism in RBP4, FSHB) or PCR (insertion/deletion in EGF) methods. Obtained result showed that RBP4 variants were related to total number born (TNB) and number born alive (NBA) in 1st, 2nd and 5th parities, FSHB to TNB and NBA in first two parities, however EGF with both traits in all parities (P≤0.05 or P≤0.01). In case of RBP4 gene, heterozygous genotype (AB) was favorable for analyzed traits, however in case of FSHB and EGF homozygous genotype, AA and BB respectively. Obtained results indicate that polymorphism in three analyzed genes is associated with important reproductive traits of pigs kept in Poland.

Taking a DNA-sequence, a word with letters/bases A, T, G and C, as the relation between the generators of an infinite group $\pi$, one can discriminate two important families: (i) the cardinality structure for conjugacy classes of subgroups of $\pi$ is that of a free group on $1$ to $4$ bases and the DNA word, viewed as a substitution sequence, is aperiodic. (ii) The cardinality structure for conjugacy classes of subgroups of $\pi$ is not that of a free group, the sequence is generally not aperiodic and topological properties of $\pi$ have to be determined differently. The two cases rely on DNA conformations such as A-DNA, B-DNA, Z-DNA, G-quadruplexes, etc. We found a few salient results: Z-DNA, when involved in transcription, replication and regulation in a healthy situation implies (i). The sequence of telomeric repeats comprising $3$ distinct bases, most of the time, satisfies (i). For $2$-base sequences in the free case (i) or non free case (ii), the topology of $\pi$ may be found in terms of the $SL(2,\mathbb{C})$ character variety of $\pi$ and the attached algebraic surfaces. The linking of two unknotted curves --the Hopf link-- may occur in the topology of $\pi$ in cases of biological importance, in telomeres, G-quadruplexes, hairpins and junctions, a feature we already found in the context of models of topological quantum computing. For $3$- and $4$ base sequences, other knotting configurations are noticed and a building block of the topology is the $4$-punctured sphere. Our methods have the potential to discriminate potential diseases associated to the sequences.

Ribonucleoproteins (RNP) condensates often contain intrinsically disordered proteins (IDPs) able to confer an exceptional multifunctionality necessary for gene expression, a process that defines cell types and enables cellular adaptation in metazoans. Centosomes, the microtubule-organizing centers of animal cells, are particularly enriched in disordered proteins but the role of RNPs surrounding the centrosome and the ciliary basal body remains largely unknown. By refining and integrating the existing protein-protein interaction network, spatial proteomics and transcriptomic data, we here report the subcellular and genomic proximity between the spliceosome, a huge nuclear RNP complex that removes introns from a transcribed pre-mRNA, and centrosome/cilia components. We present a comprehensive map of pre-RNA processing factors and other RNA-binding proteins playing a role in the regulation of splicing but localized to the centrosome and cilia. Protein-protein interactions studies reveal that a large number of spliceosome components interact with both centrosome linker and centriolar satellites elements, necessary for cellular division and ciliogenesis. RNAseq data from mouse Embryonic Stem Cells (mESC) and human tissues revealed a co-transcriptional coordination program of splicing and centrosome-related genes with relevance to tissue-specific neurosensory disorders and cancer types. Additionally, we found that centrosome and spliceosome genes form linearly and spatially colocalized genomic loci (CEP250, RBBM39, DHX35, and CTNNBL1) conserved in human and mouse genome, then explaining similarities in co-modification and subcellular distribution. Our results suggest that centrosome and cilia constitute cytoplasmic sites for the exchange of molecular machinery with nucleus, storage of RNA splicing and spliceosome condensates previously unrecognized. These complexes in response to external signals, could play an integral part in ciliogenesis and nuclear division to establish and maintain cellular identity in metazoans.

Fibroepithelial lesions (FL) of the breast, in particular Phyllodes tumors (PT) and fibroadenomas, pose a significant diagnostic challenge. There are no generally accepted criteria that distinguish benign, borderline, malignant PT, and FA. Combined genome-wide DNA methylation and copy number variant (CNV) profiling is an emerging strategy to classify tumors. We compiled a series of patient-derived archival biopsy specimens reflecting the FL spectrum and histological mimickers including clinical follow-up data. DNA methylation and CNVs were determined by well-established microarrays. Comparison of the patterns with a pan-cancer dataset assembled from public resources including "The Cancer Genome Atlas" (TCGA) and "Gene Expression Omnibus" (GEO) suggests that FLs form a methylation class distinct from both control breast tissue as well as common breast cancers. Complex CNVs were enriched in clinically aggressive FLs. Subsequent fluorescence in situ hybridization (FISH) analysis detected respective aberrations in the neoplastic mesenchymal component of FLs only, confirming that the epithelial component is non-neoplastic. Of note, our approach could lead to the elimination of the diagnostically problematic category of borderline PT and allow for optimized prognostic patient stratification. Furthermore, the identified recurrent genomic aberrations such as 1q gains (including MDM4), CDKN2a/b deletions and EGFR amplifications may inform therapeutic decision-making.

Exosomes are nano-sized extracellular vesicles excreted by mammalian cells that circulate freely in the bloodstream of living organisms. Exosomes have a lipid bilayer that encloses genetic material used in intracellular communication (e.g., double-stranded DNA, micro-RNAs, and messenger RNA). Recent evidence suggests that dysregulation of this genetic content within exosomes has a major role in tumor progression and in the surrounding microenvironment. Motivated by this discovery, we focused here on using exosomal biomarkers as a diagnostic and prognostic tool for cancer. In this review, we discuss recently discovered exosome-derived proteomic and genetic biomarkers used in cancer diagnosis and prognosis. Although several genetic biomarkers have been validated for their diagnostic values, proteomic biomarkers are still being actively pursued. We discuss both commercial technologies and emerging technologies for exosome isolation and analysis.

Every firm is devoted to polishing and fine-tuning its maintenance strategy. More exactly, when we develop robust and efficient preventive and conditional maintenance approaches, our objective is to combine performance and robustness to increase maintenance decision-making. This, in turn, leads to a reduction in system failures and a subsequent drop in related expenses. This impulse drives the origin of this essay: to provide fresh criteria that allow us to improve and optimize maintenance techniques. Furthermore, our study has been realistically utilized via the deployment of condition-based maintenance (CBM) techniques, which are commonly regarded as a critical lever that allows firms to gain a competitive advantage in the context of the fourth industrial revolution. Combining both perfect and imperfect maintenance actions into CBM strategies appears to be an effective technique to obtain high economic performance and robustness in the maintenance strategies of the companies. Following this idea, we propose and optimize in this paper a set of criteria enabling the combined assessment of the mean economic performance and the resilience of various kinds of maintenance techniques. The advantage of the proposed criterion is that it adapts to different types of maintenance strategies and provides access to a simple and relevant evaluation model. Thanks to this new criterion, we will be able to choose the better maintenance strategies that have more performance and robustness between these strategies for a system with more or less stable behavior. The Monte Carlo Method is incorporated into the comparative assessment of maintenance methods, adding a layer to the evaluation of the performance and robustness of each adaptation in decision-making.

Using the nematode C. elegans germline as a model system, we previously reported that PUF-8 (a PUF RNA-binding protein) and LIP-1 (a dual-specificity phosphatase) repress sperm fate at 20°C and the dedifferentiation of spermatocytes into mitotic cells (termed "spermatocyte dedifferentiation") at 25°C. Thus, double mutants lacking both PUF-8 and LIP-1 produce excess sperm at 20°C, and their spermatocytes return to mitotically dividing cells via dedifferentiation at 25°C, resulting in germline tumors. To gain insight into the molecular competence for spermatocyte dedifferentiation, we compared the germline phenotypes of three mutant strains – fem-3(q20gf), puf-8(q725; fem-3(q20gf), and puf-8(q725); lip-1(zh15). Both fem-3(q20gf) and puf-8(q725); fem-3(q20gf) mutants produced excess sperm like puf-8(q725); lip-1(zh15) double mutants. Our results show that spermatocyte dedifferentiation was not observed in fem-3(q20gf) mutants, but it was more aggressive in puf-8(q725); lip-1(zh15) than in puf-8(q725); fem-3(q20gf) mutants. These results suggest that MPK-1 (the C. elegans ERK1/2 MAPK ortholog) activation by removing the function of LIP-1 in the absence of PUF-8 promotes spermatocyte dedifferentiation. This idea was confirmed using Resveratrol (RSV), a potential activator of MPK-1 and ERK1/2 in C. elegans and human cells. Notably, spermatocyte dedifferentiation was significantly enhanced by RSV treatment, and its effect was blocked by mpk-1 RNAi. We, therefore, conclude that PUF-8 and MPK-1 are normally required to inhibit spermatocyte dedifferentiation and tumorigenesis. Since these regulators are broadly conserved, we suggest that similar regulatory circuitry may control cellular dedifferentiation and tumorigenesis in other organisms, including humans.

In coastal areas around the world, seagrass meadows play a crucial ecological and economic role. A large amount of seagrass beds dominates primary production and contributes to the high secondary productivity of this ecosystem. The microbial loop (consuming bacterial biomass by grazers and using seagrass-derived detritus by bacteria) may be an important mechanism for transferring seagrass-derived organic matter to the aquatic food chain. This study aims to improve our understanding of how bacterial growth and mortality (grazing and viral lysis rates) differ in seagrass and adjacent unvegetated meadow habitats. We found that viral lysis and grazing caused similar mortality rates of bacteria in a seagrass environment during the summer. It has been found, however, that bacterial production is controlled by the availability of resources (bottom-up control) and is cycled within the bacteria-virus-DOC loop in adjacent unvegetated waters. Our study region may be affected by this shift in organic matter fate and cycling.

Neurodegenerative diseases (NDs) affect millions of people worldwide, and to date Alzheimer's and Parkinson's disease are the most common NDs. The risk of developing NDs increases dra-matically with age, and genetic and environmental factors can be crucial in their progression. The main feature of NDs is the abnormal presence of specific proteins that can lead to neuronal death, proteotoxic stress, and alteration of catabolic systems, which are major players in the processes of neurodegeneration and neuroinflammation. Despite research efforts to date, the therapies cur-rently in use for the treatment of NDs provide marginal therapeutic benefit, so the focus is now being direct toward the search of natural products that could be a valuable aid in combating these diseases, including the natural compound Andrographis paniculata (Ap) and especially its main constituent Andrographolide (Andro). Preclinical studies have shown that the aqueous extract of Ap is capable to modulate neuroinflammatory and neurodegenerative responses, determining a reduction in inflammatory markers and oxidative stress in various NDs. Therefore, in this review we will focus on the molecular mechanisms through which Ap and Andro are able to modulate the processes of neurodegeneration and neuroinflammation that are major causes of neuronal death and cognitive decline.

Background: We screened key genes involved in the dedifferentiation process of thyroid cancer by analyzing differentially expressed genes in anaplastic thyroid carcinoma (ATC) using Gene Expression Omnibus (GEO) database. Methods: We analyzed differentially expressed genes in ATC from GEO database and constructed a co-expression network using Weighted Gene Co-expression Network Analysis (WGCNA) . Cytoscape was used to calculate top ten key genes based on their gene scores. DEPDC1 was selected as interest gene for further validation, including examination of its prognostic relationship with thyroid cancer, correlation analysis with thyroid differentiation markers, immune cell infiltration, and tumor microenvironment. The impact of DEPDC1 on cancer cell migration, invasion, and proliferation was validated through downregulation and overexpression of DEPDC1 gene in thyroid cancer cell lines c643 and BCPAP. Results: We identified top 10 key genes in ATC: AURKA, TPX2, RACGAP1, MELK, DLGAP5, DEPDC1, KIF2C, NCAPG, CCNB1, and PBK. DEPDC1 showed a strong correlation with the prognosis of thyroid cancer. The odds ratio (OR) for overall survival was 3.5 (P=0.016) in individuals with high DEPDC1 expression, and the OR for disease-free survival was 2.6 (P=0.003). Additionally, the analysis revealed a significant negative correlation between the expression of DEPDC1 and thyroid differentiation markers. Gene Ontology enrichment analysis demonstrated that DEPDC1 co-expressed genes were enriched in cellular processes, cell cycle pathways, and dynamic protein groups. Matrix and immune scoring indicated tumor microenvironment and immune scores were associated with DEPDC1 expression. TIMER2.0 online analysis revealed a strong correlation between DEPDC1 expression and immune cell infiltration in papillary thyroid carcinoma. After downregulation of DEPDC1 expression, the invasion, migration, and proliferation abilities of tumor cells were significantly reduced. Conversely, overexpression of DEPDC1 exhibited the opposite effect. Conclusion: DEPDC1, a newly identified dedifferentiation gene in thyroid cancer, inversely correlated with the degree of differentiation. High expression of DEPDC1 promotes cancer progression and leads to poor prognosis in thyroid cancer.

DEXTER (Detection of EXplosives and firearms to counter TERrorism) is a project funded by NATO’s Science for Peace and Security (SPS) program with the goal of developing an integrated system capable of remotely and accurately detecting explosives and firearms in public places without impeding the flow of pedestrians. The active microwave component of the DEXTER project is referred to as MIC (Microwave Imaging Curtain), supported by the French SGDSN (General Secretariat of Defense and National Security), and utilizes a radar system capable of generating 3D images in real time to address non-checkpoint detection of explosives and fire-arms. The project, led by the ONERA (France), is based on a radar imaging system developed by the Fraunhofer FHR institute, using a MIMO architecture with an Ultra Wide-Band waveform. Although high-resolution 3D microwave imaging is already being used in expensive body scanners to detect firearms concealed under clothing, MIC's innovative approach lies in utilizing a high-resolution 3D imaging device that can detect larger dangerous objects carried by moving individuals at a longer range, in addition to providing discrete detection in pedestrian flow. Automatic detection and classification of these dangerous objects is carried out on 3D radar im-ages using a deep-learning network. This paper will outline the project's objectives and constraints, as well as the design, architecture, and performance of the final system. Additionally, it will present real-time imaging results ob-tained during a live demonstration in a relevant environment.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering.’

Holographic subsurface radar (HSR) is currently not in widespread usage. This is due to an historical perspective in the ground penetrating radar (GPR) community that the high attenuation of electromagnetic waves in most media of interest, and the inability to apply time-varying gain to the continuous wave (CW) HSR signal precludes sufficient effective penetration depth. While it is true that the fundamental physics of HSR, with its use of a CW signal, does not allow amplification of later (i.e. deeper) arrivals in lossy media (as is possible with impulse subsurface radar — ISR), HSR has distinct some distinctive advantages. The most important of these is the ability to do shallow subsurface imaging with a resolution that is not possible with ISR. In addition, the design of an HSR system is simpler than for ISR due to the relatively low-tech transmitting and receiving antennae. This paper provides a review of the main principles of HSR through an optical analogy and describes possible algorithms for radar hologram reconstruction. We also present a review of the history of development of systems and applications for HSR of the “RASCAN” type which is possibly the only holographic subsurface radar that is produced in lots. Among the subsurface imaging and remote sensing applications considered are humanitarian demining, construction inspection, surveys of historic architecture and artworks, nondestructive testing of dielectric aerospace materials, security applications, paleontology, detection of wood-boring insect damage, and others. Each application is illustrated with relevant data acquired in laboratory and/or field experiments.

Holographic subsurface radar (HSR) is currently not in widespread usage. This is due to an historical perspective in the ground penetrating radar (GPR) community that the high attenuation of electromagnetic waves in most media of interest, and the inability to apply time-varying gain to the continuous wave (CW) HSR signal precludes sufficient effective penetration depth. While it is true that the fundamental physics of HSR, with its use of a CW signal, does not allow amplification of later (i.e. deeper) arrivals in lossy media (as is possible with impulse subsurface radar — ISR), HSR has distinct some distinctive advantages. The most important of these is the ability to do shallow subsurface imaging with a resolution that is not possible with ISR. In addition, the design of an HSR system is simpler than for ISR due to the relatively low-tech transmitting and receiving antennae. This paper provides a review of the main principles of HSR through an optical analogy and describes possible algorithms for radar hologram reconstruction. We also present a review of the history of development of systems and applications for HSR of the “RASCAN” type which is possibly the only holographic subsurface radar that is produced in lots. Among the subsurface imaging and remote sensing applications considered are humanitarian demining, construction inspection, surveys of historic architecture and artworks, nondestructive testing of dielectric aerospace materials, security applications, paleontology, detection of wood-boring insect damage, and others. Each application is illustrated with relevant data acquired in laboratory and/or field experiments.

Nanocellulose is cellulose in the form of nanostructures, i.e. features not exceeding 100 nm at least in one dimension. These nanostructures include nanofibrils, e.g. in bacterial cellulose; nanofibers, e.g. in electrospun matrices; nanowhiskers and nanocrystals. These structures can be further assembled into bigger 2D and 3D nano-, micro- and macro-structures, such as nanoplatelets, membranes, films, microparticles and porous macroscopic matrices. There are four main sources of nanocellulose: bacteria (Gluonacetobacter), plants (trees, shrubs, herbs), algae (Cladophora) and animals (Tunicata). Nanocellulose has emerged for a wide range of industrial, technology and biomedical applications, e.g. for adsorption, ultrafiltration, packaging, conservation of historical artifacts, thermal insulation and fire retardation, energy extraction and storage, acoustics, sensorics, controlled drug delivery, and particularly for tissue engineering. Nanocellulose is promising for use in scaffolds for engineering of blood vessels, neural tissue, bone, cartilage, liver, adipose tissue, urethra and dura mater, for repairing connective tissue and congenital heart defects, and for constructing contact lenses and protective barriers. This review is focused on applications of nanocellulose in skin tissue engineering and wound healing as a scaffold for cell growth, for delivering cells into wounds, and as a material for advanced wound dressings coupled with drug delivery, transparency and sensorics. Potential cytotoxicity and immunogenicity of nanocellulose are also discussed.

Clinical rehabilitation and sports performance analysis both require the objectification of movement. Kinovea^© is a free 2D motion analysis software that enables the establishment of kinematics parameters. This low-cost technology has been used in sports sciences, as well as clinical field and research work. Although it has been validated as a tool with which to assess time-related variables, this is not yet the case regarding angular and distance variables. The main objective of this study was to determine the validity and reliability of the Kinovea software in obtaining angular and distance data at different perspectives of 90°, 75°, 60° and 45°. For this purpose, a figure with 29 points was designed (in AutoCAD) and 24 frames analysed. Each frame was examined by three observers who each made two attempts. For each export data item, 20 angles and 20 distance variables were calculated, with intra- and inter-observer reliability also analysed. To evaluate Kinovea reliability and validity a multiple approach was applied involving the following analysis: -systematic error with a two-way ANOVA 2x4; -relative reliability with ICC and CV (95% confidence interval); -absolute reliability with Standard Error. The results thus obtained indicate that the Kinovea software is a valid and reliable tool that is able to measure accurately at distances up to 5 m from the object and at an angle range of 90°–45°. Nevertheless, for optimum results an angle of 90° is suggested.

The relationship between tissue effects, intensity (I), and voltage (V) of a high-frequency alternative current seems well known. However, the translation of the settings of the electrosurgical unit and their use during surgery seems not to be unanimously understood by all surgeons. This results in many variations of surgical technique and plenty of specific questions asked during live surgery. Above 200 V, the heat of the sparks results in the explosion of superficial cells and a cutting effect. With higher voltages, the associated coagulation is increasing. Voltage and amount of energy (Watt=I*V) are independent since a similar amount of energy can be obtained with a continuous current or an intermittent current half the time and a double voltage. Below 200 V, tissue is heated until the steam from boiling tissue stops the current. Therefore, slower heating with less energy or a larger contact area permits deeper coagulation. The maximal output (W) of the electrosurgical unit results in versatility of use besides being a safety measure. The current intensity increases with the area of contact. Therefore, when I*V exceeds the preset output, V has to drop. A limited maximal output thus permits using the same instrument for non-contact cutting with >200V and sparks and coagulation when the contact area is much larger. In conclusion, the tissue effects of electrosurgery vary with the device’s voltage setting (often indicated as force) and the maximal output. The sur-geon’s choice to cut or coagulate by changing the contact area adds versatility.

A global existential and interlocking environmental, climate and cooperation/equity polycrisis is being faced, which increasingly impacts and is impacted by water and land systems. As a result, transformations in response are gaining increasing traction. Advances in approaches to visualising and communicating how innovations and changes in landscape features enable shifts, transformations and transitions are more crucial than ever before. Visions help focus actions, collaboration and alignment of multiple actors in working towards a common purpose, whilst also entering people’s consciousness at the deep level of values, transforming beliefs and consequently, thinking and action. They give direction on effort and pull on transformational innovation. The evidence-based ‘Water Visions Visualisation Platform’ presents an innovative and accessible way to illustrate, communicate and support future water visioning and strategizing at the landscape scale based on composite paradigms, scenarios, horizons and concepts. Plausible visions of the future are envisioned, illustrated, narratively described and qualitatively assessed, as well as connected with real-world examples and resources through the interactive Platform. This paper outlines the co-creation methodology, the architecture and the co-development of the Platform, as well as a preliminary evaluation through literature-based criteria and the sharing of the Platform with a number of audiences.

Background: Using the COM-B model as a framework, an EU-wide survey aimed to ascertain multidisciplinary healthcare workers’ (HCWs) knowledge, attitudes and behaviours on antibiotics, antibiotic use and antibiotic resistance. The UK findings are presented. Methods: A 43-item questionnaire was developed through a two-round modified Delphi consensus process. The UK target quota was 1,315 respondents. Results: 2,404 participants responded. The highest proportion were nursing and midwifery professionals (42%), pharmacists (23%) and medical doctors (18%). HCWs correctly answered that antibiotics are not effective against viruses (97%), they have associated side effects (97%), unnecessary use makes antibiotics ineffective (97%) and healthy people can carry antibiotic resistant bacteria (90%). However, fewer than 80% correctly answered that using antibiotics increases a patient’s risk of antimicrobial resistant infection or that resistant bacteria can spread from person to person. Whilst the majority of HCWs (81%) agreed there is a connection between their antibiotic prescribing behaviour and the spread of antibiotic resistant bacteria, only 64% felt that they have a key role in controlling antibiotic resistance. The top three barriers to providing advice or resources were lack of resources (19%), insufficient time (11%) and the patient being uninterested in the information (7%). Approximately 35% of UK respondents who were prescribers prescribed an antibiotic at least once in the last week due to fear of patient deterioration or complications. Conclusion: These findings highlight that a multifaceted approach to tackling the barriers to prudent antibiotic use in the UK is required and provides evidence for guiding targeted policy, intervention development and future research. Education and training should focus on patient communication, information on spreading resistant bacteria and increased risk for individuals.

COVID-19 pandemic in first seven months has led to more than 15 million confirmed infected cases and 600,000 deaths. SARS-CoV-2, the causative agent for COVID-19 has proved a great challenge for its ability to spread in asymptomatic stages and a diverse disease spectrum it has generated. This has created a challenge of unimaginable magnitude not only affecting human health and life but also potentially generating a long-lasting socioeconomic impact. Both medical sciences and biomedical research have also been challenged consequently leading to a large number of clinical trials and vaccine initiatives. While known proteins of pathobiological importance are targets for these therapeutic approaches, it is imperative to explore other factors of viral significance. Accessory proteins are one such trait that have diverse roles in coronavirus pathobiology. Here we analyze certain genomic characteristics of SARS-CoV-2 accessory protein ORF8, predict upon its protein features and review current available literature regarding its function. We have also undertaken review of ORF8 homolog ORF8ab from SARS-CoV with a purpose of developing holistic understanding of these proteins for reason that coronaviruses have been infecting humans repeatedly and might continue to do so. Despite low nucleotide and protein identity and differentiating genome level characteristics, there appears to be significant structural integrity and functional proximity between these proteins pointing towards their high significance. There is further need for comprehensive genomics and structural-functional studies to lead towards definitive conclusions regarding their criticality and that can eventually define their relevance to therapeutics development.

Sulfur, peroxide and combined sulfur and peroxide curing systems were applied for cross-linking of unfilled and carbon black filled rubber compounds based on ethylene-propylene-diene-monomer rubber. The results revealed that the type of curing system influenced the course and shape of curing isotherms. This resulted in the change of curing kinetics of rubber compounds. The cross-link density of vulcanizates cured with combined vulcanization systems was lower than that for vulcanizates cured only in the presence of sulfur or peroxide system. The results revealed good correlation between the cross-link density as well as the structure of the formed cross-links and physical-mechanical characteristics of the materials. It can be stated that by proper combination of vulcanization systems it is possible to modify tensile behavior of vulcanizates in targeted manner. On the other side, dynamical-mechanical properties were found not be significantly influenced by the composition of curing system.

Bees (Apoidea), the largest and most crucial radiation of pollinators, play a vital role in ecosystem balance. Transposons are widely distributed in nature and are important drivers of species diversity. However, transposons are rarely reported in important pollinators such as bees. Here, we surveyed 37 genomes in Apoidea, annotated the pogo and Tc1/mariner transposons in the genome of each species and performed a phylogenetic analysis to determine their overall distribution. The pogo and Tc1/mariner families showed high diversity and low abundance in the 37 species, and their proportion was significantly higher in solitary bees than in social bees. DD34D/mariner was found to be distributed in almost all species and was found in Apis mellifera, Apis mellifera carnica, Apis mellifera caucasica and Apis mellifera mellifera and Euglossa dilemma may still be active. Using horizontal transfer analysis, we found that DD30D/Tigger, DD33D/Tigger and DD34D/mariner may have experienced horizontal transfer events. The current study displayed the evolution profiles (including diversity, activity, and abundance) of the pogo and Tc1/mariner transposons across 37 species of Apoidea. Our data revealed their contributions to the genomic variations across these species and facilitated in understanding of the genome evolution of this lineage.

Particulate matter is a severe source of atmospheric pollution in urban cities, and it has adverse effects on human health. This study was conducted during the whole year of 2016 to monitor the concentrations of PM₁₀ and PM_2.5 on the Beijing Hanshiqiao wetland and bare land in Beijing to analyze their correlations with meteorological factors and compare the removal efficiency between two land surface types. The results indicated that (1) the PM₁₀ and PM_2.5 concentrations on the bare land were higher than those on wetland as a whole, reaching the highest value both at night and dusk and the lowest value near noon. The average concentration of PM₁₀ was higher in winter (wetland: 137.48 μg·m^-3; bare land: 164.75 μg·m^-3) and spring (wetland: 205.18 μg·m^-3; bare land: 244.85 μg·m^-3) and the concentration of PM_2.5 on the wetland also reached the higher value in winter and spring with the average of 84.52 μg·m^-3 and 98.98 μg·m^-3, whereas, it was higher in spring and summer on the bare land; (2) concentrations of PM₁₀ and PM_2.5 were significantly positively affected by the relative humidity (P < 0.01) and negatively influenced by wind speed (P < 0.05). The relationship between PM₁₀ and PM_2.5 concentrations and temperature was found complicated: it showed a significantly negative correlation (P < 0.01) in winter and spring and was insignificant in autumn, but in summer, only the correlation between the PM₁₀ concentration and temperature on wetland was significant (P < 0.01); (3) the removal efficiencies of PM₁₀ and PM_2.5 followed the order of spring > winter > autumn > summer on the wetland, and the removal efficiency of PM₁₀ was greater than that of PM_2.5. This study is aim to provide practical measures to improve the air quality and facilitate sustainable development in Beijing.

Osteoarthritis and rheumatoid arthritis are common cartilage and joint diseases that globally affect more than 200 and 20 million people, respectively. Several transcription factors have been implicated in the onset and progression of osteoarthritis, including Runx2, C/EBPβ, HIF2α, Sox4, and Sox11. IL-1β also leads to osteoarthritis through NF-ĸB, IκBζ, and Zn²⁺-ZIP8-MTF1 axis. IL-1, IL-6, and TNFα play a major pathological role in rheumatoid arthritis through NF-ĸB and JAK/STAT pathways. Indeed, inhibitory reagents for IL-1, IL-6, and TNFα provide clinical benefits for rheumatoid arthritis patients. Several growth factors, such as BMP, FGF, PTHrP, and Indian hedgehog, play roles regulating chondrocyte proliferation and differentiation. Disruption and excess of these signaling cause genetic disorders in cartilage and skeletal tissues. FOP, an autosomal genetic disorder characterized by ectopic ossification, is induced by mutant ACVR1. mTOR inhibitors were found to prevent ectopic ossification by ACVR1 mutations. ACH and related diseases are autosomal genetic diseases, which manifest severe dwarfism. CNP is currently the most promising therapy for ACH. In these ways, investigation of cartilage and chondrocyte diseases at molecular and cellular levels sheds light on the development of effective therapies. Thus, identification of signaling pathways and transcription factors implicated in these diseases is important.

Thalassemia is one of the most prevalent genetic disorders worldwide which has been previously found to have an association with several physiological and organ complications. Several studies found both its positive and inverse correlation with glomerular filtration rate (GFR). Therefore, in this meta-analysis, we tried to assess the accurate correlation of thalassemia with GFR. We searched in Google Scholar, PubMed, and ScienceDirect, and from the initial 96 articles we finally could include 15 studies. The quality and publication bias assessment confirmed that all the studies were of high to moderate quality with no publication bias. The main outcome of the mean difference (MD) was -6.45, 95%CI: -18.50, 5.60 (P<0.00001), which indicated a negative correlation of GFR with thalassemia. The sensitivity analyses found one study as a slight outlier and reanalyzing the data excluding that study MD was achieved as -13.90, 95%CI: -24.22, -3.59 (P<0.00001) which even strongly supports our main outcome. Our result determined that the GFR is generally higher in healthy people as compared to thalassemia patients.

Rivaroxaban and aspirin are commonly used antithrombotic agents that are used in combination for the prevention of coronary artery disease (CAD) and atherothrombotic events in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers, or with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) in high-risk patients. The recommended dosage is 2.5 mg Rivaroxaban twice daily with 75–100 mg aspirin daily. This study aimed to develop a fixed-dose combination tablet of rivaroxaban (2.5 mg) and aspirin (50 mg) to decrease the patient's pill burden and enhance medication adherence. The product formula was developed based on compatibility studies among the active ingredients and the active ingredients' compatibility studies. The formula and the manufacturing procedure were chosen based on the risk assessment for each active substance, wet granulation with both actives intragranular was found to have faster dissolution than direct mix formulae. Furthermore, a validated reverse-phase HPLC stability indicator method was developed to detect APIs and their possible degradants in the formula.

Abstract: The aim of the present study was to identify the age and sex-related associations between marital status with PA and TV time. We used data from Vigitel, an annual telephone survey started in 2006 in Brazil. We applied a complex sample logistic regression model to estimate the odds for PA and TV time comparing marital statuses according to age and sex subgroups, independent of obesity, hypertension, diabetes, self-assessed poor health, and smoking. Our sample included 561,837 individuals with a TV time &gt; 3 h/day (prevalence = 25.2%) and PA &gt; 150 min/week (prevalence = 35%). Compared to single individuals, married men and women were less likely to watch TV more than 3 h/day in participants &gt; 30 years old. When compared to single, married participants were less likely to do more than 150 min of PA/week at younger age groups. Married women older than 40 years were more likely to do more than 150 min of PA/week than the single ones, while there were no differences among married men by age group. In conclusion, married individuals are less likely to spend more than 3 hours a day watching TV than single individuals. Single men and women were more likely to do more than 150 min of PA/week at younger age groups and married women older than 40 years were more likely to do 150 min of PA/week than single women.

Medical and translational scientific research requires the use of animal models as an initial approach to the study of new therapies and treatments, but when the objective is an exploration of translational potentialities, classical models fail to adequately mimic problems in humans. Among the larger animal models that have been explored more intensely in recent decades, small ruminants, namely sheep and goats, have emerged as excellent options. The main advantages associated to the use of these animals in research works are related to their anatomy and dimensions very similar to those of humans in most physiological systems, in addition to their low maintenance and feeding costs, tendency to be docile, long life expectancies and few ethical complications raised in society. The most obvious disadvantages are the significant differences in some systems such as the gastrointestinal, and the reduced amount of data that limits the comparison between works and the validation of the characterization essays. Despite everything, recently these species have been increasingly used as animal models for diseases in different systems, and the results obtained open doors for their more frequent and advantageous use in the future. The purpose of this review is to summarize the general principles related to the use of small ruminants as animal models, with focus on regenerative medicine, to group the most relevant works and results published recently and to highlight the potentials for the near future in medical research.

Bursera fagaroides popularly used in México possess bioactive lignans. These compounds are low in the bark, and its extraction endangers the life of the trees. The aim of the present investigation was to search for alternative sources of cytotoxic compounds from B. fagaroides as leaves and in vitro callus cultures. The friable callus of B. fagaroides were established using a combination of phytoregulators: 4 mgL-1 of 2,4-dichlorophenoxyacetic acid (2,4-D), 1 mgL-1 Naphthaleneacetic Acid (NAA) and 1 mgL-1 Zeatin. The maximum cell growth was at day 28 with a specific growth rate μ= 0.059 days-1 and duplication time td=11.8 days. Scopoletin with a concentration of 10.7 µg/g dry weight was the main compound inducible as a phytoalexin by the addition of high concentrations of 2,4-D, as well as by the absence of nutrients in the culture medium. The com-pounds γ-sitosterol, and stigmasterol were also present. Open column chromatography was used to separate and identify: yatein, acetyl podophyllotoxin and 7'8'-dehydropodophyllotoxin in the leaves of the wild plant. Cytotoxic activity on four cancer cell lines was tested, being PC-3 prostate carcinoma (IC50 of 12.6±4.6) the most sensitive to the wild-type plant extract and HeLa cervical carcinoma (IC50 of 72±5) to the callus culture extract.

Paenibacilli are efficient producers of potent agents against bacterial and fungal pathogens, which are of great interest both for therapeutic applications in medicine as well as in agrobiotechnol-ogy. Lipopeptides produced by such organisms play a major role in their inactivation potential. In this work we investigated two lipopeptide complexes, the fusaricidins and the polymyxins, produced by Paenibacillus polymyxa strains DSM 32871 and M1 by MALDI-TOF mass spectrometry. The fusaricidins show potent antifungal activities and are distinguished by an unusual variabil-ity. For strain DSM 32871 we identified numerous yet unknown variants mass spectrometrically. DSM 32871 produces polymyxins of type E (colistins), while M1 forms polymyxins P. For both strains novel, but not yet completely characterized polymyxin species were detected, which pos-sibly are glycosylated. These compounds may be of interest therapeutically, because polymyxins attain increasing attention as last-resort antibiotics against multiresistant pathogenic Gram-negative bacteria. In addition, the volatilomes of DSM 32781 and M1 were investigated with a GC-MS approach using different cultivation media. Production of volatile organic com-pounds (VOCs) was strain and medium dependent. In particular, strain M1 manifested as an effi-cient VOC-producer that exhibited formation of 25 volatiles in total. A characteristic feature of Paenibacilli is the formation of volatile pyrazine derivatives.

With the increased scientific interest in green technologies, many researches have been focused on the production of polymeric composites containing naturally occurring reinforcing particles. Apart from increasing mechanical properties, these additions can have a wide range of interesting effects, such as increasing the resistance to bacterial and fungal colonization. In this work, different amounts of two different natural products, namely neem and turmeric, have been added to polyethylene to act as a natural antibacterial and antifungal product for food packaging applications. Microscopic and spectroscopic characterization showed that fractions up to 5% of these products can be dispersed into low-molecular weight polyethylene, while higher amounts could not be properly dispersed and resulted in an inhomogeneous, fragile composite. In vitro testing conducted with Escherichia coli, Staphylococcus aureus and Candida albicans showed a reduced proliferation of pathogens when compared to the polyethylene references. In particular, turmeric, resulted to be more effective against E. coli when compared to neem, while they had similar performances against S. aureus. Against C. albicans, only neem was able to show a good antifungal behavior, at high concentrations. Tensile testing showed that the addition of reinforcing particles reduces the mechanical properties of polyethylene, and, in the case of turmeric, it is further reduced by UV irradiation.

The emergence of cloud computing, big data analytics, and machine learning has catalysed the use of remote sensing technologies to enable more timely land management of sustainability indicators such as ground cover and grassland biomass, given the uncertainty of future climate and drought conditions. Here, we examine the potential of “regenerative agriculture”, as an adaptive grazing management strategy to minimise bare ground exposure while maximising pasture biomass productivity. High-intensity sheep grazing treatments were conducted in small fields (less than 1 hectare) for short durations (typically less than 1 day). Paddocks were subsequently spelled to allow pasture biomass recovery (treatments comprising 3, 6, 9, 12, and 15 months) with each compared with control treatments with lighter stocking rates for longer periods (2,000 DSE). Pastures were composed of wallaby grass (Austrodanthonia species), kangaroo grass (Themeda triandra), Phalaris (Phalaris aquatica, and cocksfoot (Dactylis glomerata) were destructively sampled to estimate total standing dry matter (TSDM), standing green biomass, standing dry biomass and trampled biomass. We then invoked a machine learning model using Sentinel-2 imagery to quantify TSDM, standing green biomass and standing dry biomass. Faced with La Nina conditions, regenerative grazing did not significantly impact pasture productivity, with all treatments showing similar TSDM and green biomass. However, regenerative treatments significantly impacted litter fall and trampled material, with the high intensity grazing treatments causing more dry matter trampling, increasing litter, enhancing decomposition rates and surface organic matter. Pasture digestibility was greatest for treatments with minimal spelling (3 months), whereas both standing senescent and trampled material were significantly greater for the treatment with 15-month spell periods. Estimates of TSDM using machine learning with Sentinel-2 imagery underestimated TSDM in treatment plots but explained spatiotemporal variability associated within and across treatments. The root mean square error between the measured and modelled TSDM was 903 kg DM/ha, which was less than the variability measured in the field. We conclude that regenerative grazing with short recovery periods (3-6 months) are most conducive to increasing pasture production under high rainfall conditions, and we speculate that high intensity grazing is likely to positively impact on soil organic carbon through increased litterfall and trampling. Our study paves the way forward for using machine learning with satellite imagery to quantify pasture biomass at small scales, enabling management of pastures from afar.

The interest in natural remedies in modern medicine has revealed potent disease-fighting agents, such asCUR(CUR) and nicotinamide (NIC), known for their antioxidant, anti-inflammatory, and immune-boosting properties. This study explores the antibacterial and antimelanoma potential of a CUR-NIC combination and its liposomal formulation. The antibacterial efficacy was assessed against skin infection-causing bacteria, Staphylococcus aureus, while cytotoxicity and migration assays were conducted on the melanoma B16 cancer cell line. The CUR-NIC combination (1:1) demonstrated an inhibition zone of 18±0.8 mm against S. aureus and a MIC of 31.25 µg/ml, outperforming CUR alone. Whereas Lip-CUR-NIC showed an inhibition zone of 12±0.8 mm against S. aureus and a MIC of 37.5 µg/ml. Notably, the cytotoxicity assay revealed that the CUR-NIC duo synergistically inhibited melanoma cell proliferation (CI<1). Liposomal preparations further enhanced this effect, with Lip-CUR-NIC showing a remarkably low IC50 of 8.5 ± 0.3 µM compared to CUR (IC50= 9.8 ± 2.2 µM) and NIC (IC50=135.95 ± 10.2 µM). These findings highlight the synergistic potential of CUR and NIC, especially in their liposomal form, offering a promising strategy for more effective cancer treatment.

The use of plant-based and microorganism-based biological inputs is a sustainable agricultural practice, promoting a suitable and better utilization of non-renewable resources in the environment. The benefits of using microorganisms are associated with both direct and indirect mechanisms, primarily related to improvements in nutrient absorption and availability, as well as plant growth. The main benefits of using biochemical pesticides are the promotion of sustainability and the management of resistance. Although the use of microorganisms and botanical metabolites is a promising agricultural alternative, it is still primarily concentrated in grain crops. However, due to the wide range of mechanisms of action of plant-based and microorganism-based biological inputs, there is an opportunity to expand their use in agriculture. In the Brazilian biological inputs market, various terminologies have been used to characterize biological-based products, with many of these terms being employed incorrectly and sometimes conflicting with the country’s legislation. Therefore, this review presents the classes of biological inputs and the application and evolution of the plant-based and microbiological-based product market in different crops in Brazil.

Influenza A viruses (IAVs) evolve via point mutations and reassortment of viral gene segments. The patterns of reassortment in different host species differ considerably. We investigated the genetic diversity of IAVs in wild ducks and compared it with the viral diversity in gulls. The complete genomes of 38 IAVs of H1N1, H1N2, H3N1, H3N2, H3N6, H3N8, H4N6, H5N3, H6N2, H11N6 and H11N9 subtypes isolated from wild mallard duck and gull habitants of a pond in Moscow city, Russia were sequenced. The sequences were closely related to those of avian IAVs isolated in Sweden and the Netherlands. The analysis of phylogenetic trees showed that stable viral genotypes do not persist from year to year in ducks owing to frequent gene reassortment. For comparison, similar analyses were carried out using sequences of IAVs isolated in the same period from ducks and gulls in the Netherlands. Our results revealed a significant difference in diversity and rates of reassorment of IAVs in ducks and gulls.

This paper analyses the design and implementation of REDD+ in the West African region, an important global biodiversity area. Drawing on in-depth interviews, analysis of policy documents and observation of everyday activities, we sought to understand how REDD+ has been designed and implemented in Nigeria and Ghana. We draw on tools from political ecology to examine how, and why REDD+ takes the form it does in these countries. We focus on three key dimensions that emerged as strong areas of common emphasis in our case studies -- capacity building, carbon visibility, and property rights. First, we show that, while REDD+ design generally foregrounds an ostensible inclusionary politics, its implementation is driven through various forms of exclusion. This contradictory inclusion-exclusion politics, which is partly emblematic of the neoliberal provenance of the REDD+ policy, is also a contingent reality and a strategy for navigating complexities and pursuing certain interests. Second, we show that though the emergent foci of REDD+ implementation in our case studies align with global REDD+ expectations, they yet manifest as historically and geographically contingent processes that reflect negotiated and contested relations among actors that constitute the specific national circumstance of each country. We conclude by reflecting on the wider implications of these findings for understanding REDD+ implementation more broadly.

In recent years, green and healthy foods have attracted much attention. Plant-based foods have become a new trend to replace animal-derived foods. In this study, we used walnut and purple rice as the primary raw materials to produce yogurt. The process included boiling, mixing, grinding, inoculation, fermentation, and sterilization. We then analyzed the similarities and differences between the resulting walnut purple rice yogurt and unfermented walnut purple rice milk, as well as dairy-based yogurt, in terms of physical chemistry, flavor, and sensory characteristics. We also examined the similarities and differences between fermented walnut purple rice milk and conventional warm yogurt. The study results revealed that walnut purple rice yogurt exhibited greater viscosity than walnut purple rice milk and conventional dairy-based yogurt. Additionally, the former displayed enhanced stability and recovery ability. Notably, distinguishable differences were observed between the three types of yogurts in terms of the presence of unknown volatiles and the umami signal as indicated by electronic nose/tongue and GC-IMS analyses. The umami flavour of walnut purple rice yogurt surpasses that of traditional dairy-based yogurt, whilst its salty taste is lower than that of walnut purple rice milk. Despite possessing a weaker aroma than dairy-based yogurt, it is more potent than walnut purple rice milk. Additionally, its relative abundance of olefins, ketones, and alcohols enhances its unique flavour profile, surpassing both other options. Based on sensory analysis, it can be deduced that walnut purple rice yogurt has the highest overall acceptance rate.

As a result of this work, a previously unreported benzoxazine monomer based on 3,3'-dichloro-4,4'-diaminodiphenylmethane was obtained, characterized by 1H and 13C NMR spectroscopy, and its thermal and rheological properties were studied. A comparison between the properties of benzoxazines based on diamines (3,3'-dichloro-4,4'-diaminodiphenylmethane and 4,4’-diaminodimethylmethane). The effect of the reaction medium on the structure of the oligomeric fraction and the overall yield of the main product was studied. The synthesized monomers can be used as thermo- and fire-resistant binders for polymer composite materials, as well as hardeners for epoxy resins.

This paper investigates the randomly stopped sums, minima and maxima of heavy- and light-tailed random variables. The conditions on the primary random variables, which are independent but generally not identically distributed, and counting random variable are given in order that the randomly stopped sum, random minimum and maximum is heavy/light tailed. The results generalize some existing ones in the literature. The examples illustrating the results are provided.

Most head and neck cancers are diagnosed in advanced stages, when the curative interventions are no longer possible. The assessment and the multidisciplinary therapeutic approach of the locally advanced cases are difficult since the onset of the disease becomes a significant challenge for the whole attending team (including both the patient and his family) because they have to deal with to an extensive symptomatology (abundant secretions, refractory pain, mutilations predominantly in the cephalic area), with the cure of stomas (tracheostomy, gastrostomy) and with various post-therapeutic sequelae. The present paper reflects the impact of late diagnosis, the complexity of the multimodal specific oncological treatment (chemotherapy, radiotherapy, immunotherapy, pal-liative and terminal treatment), the adaptation of medical care to the psycho-emotional structure, having as an example the case of 54-year old patient (with his consent) diagnosed with pharyn-golaryngeal neoplasm who presented himself to “St. Luca” Chronic Disease Hospital, the Oncol-ogy-Palliative Care Department, in September 2021. In patients with locally advanced head and neck cancers, besides the specifically oncological therapeutic decisions, the empathic-emotional connection between the medical team with the patient and his family plays a key role in the ther-apeutic conduct.

Honey is a very cost-efficient food source and a valuable export for the country of Uganda, but is commonly adulterated, resulting in consumers not being aware of the contents of their honey. As a result, it is important to be able to authenticate the honey that consumers are purchasing. This study evaluated the physicochemical properties (pH, free acidity, metal determination, moisture content, and FTIR spectra) of Ugandan and Manuka honey. Honey pH values ranged from 3.3 to 4.8 (±0.6) while free acidity values ranged from 34.87 to 62.22 (±8.69). The moisture content values of all honey samples were below 22%. The metal concentrations and functional groups present in Ugandan and Manuka honey were determined. Metal analysis by atomic absorption spectrometry detected five elements (Na, Ca, K, Cu, and Pb) in all honey samples in varying concentrations. The elemental concentrations were found in descending order as follows: sodium (Na) (9.38 ppm), calcium (Ca) (4.99 ppm), potassium (K) (2.48 ppm), copper (Cu) (1.87 ppm), lead (Pb) (0.28 ppm). FTIR analysis revealed similar patterns of spectral curve (O-H stretching and C-H stretching) across all honey samples analyzed, which is consistent with previously analyzed honey samples from other studies. Ugandan honey sample 7 collected in the Masaka Region was found to be most similar to the Manuka honey standard based on its observed physiochemical properties. All properties analyzed suggested Ugandan honey is of good quality and safe for consumption.

Background: Meniere disease (MD) is an inner ear disorder associated with comorbidities such as autoimmune diseases or migraine. This study describes clinical and cytokine profile in MD according to the age of onset of the condition. Methods: A cross-sectional study including 83 MD patients: 44 with early onset MD (EOMD, <35 years old), and 39 with late onset MD (LOMD, > 50 years old), 64 patients with migraine and 55 controls was carried out. Clinical variables and cytokines levels of CCL3, CCL4, CCL18, CCL22, CXCL1 and IL-1β were compared among the different groups. Results: CCL18 levels were higher in patients with migraine or MD than in controls. Elevated levels of IL-1β were observed in 11.4% EOMD and in 10.3% LOMD patients and these levels were not dependent on the age of individuals. EOMD had a longer duration of the disease (p=0.004) and a higher prevalence of migraine than LOMD (p=0.045). Conclusions: Patients with EOMD have a higher prevalence of migraine than LOMD, but migraine is not associated with any cytokine profile in patients with MD. The levels of CCL18, CCL3 and CXCL4 were different between patients with MD or migraine and controls.

The stepwise hydrogenation of the C=C bond and C=O group of acrolein on Au₃ and Au₅ model systems is investigated using the density functional theory(DFT) PW91 functional. Our results show that the C=C hydrogenation is more favorable than that of C=O bond on Au₃ with the barriers of the rate-determining step being 0.35 and 0.62 eV respectively. On the other hand, the C=O reduction is preferred over the hydrogenation of the C=C bond on Au₅. The corresponding barriers of the rate-determining steps are 0.45 and 0.54 eV, respectively. This demonstrated that the second hydrogenation step controls the reaction on both Au₃ and Au₅ for C=O and C=C hydrogenation and the C=O hydrogenation on Au₅ is preferred over the hydrogenation of the C=C bond, which is helpful to address the reactivity of small size-selected supported gold clusters.

Cellular senescence accumulates with age and has been shown to impact numerous physiological and pathological processes, including immune function. The role of cellular senescence in cancer is multifaceted, but the impact on immune checkpoint inhibitor response and toxicity has not been fully evaluated. In this review, we evaluate the impact of cellular senescence in various biological compartments, including the tumor, the tumor microenvironment, and the immune system on immune checkpoint inhibitor efficacy and toxicity. We provide an overview of the impact of cellular senescence in normal and pathological contexts and examine recent studies that have connected aging and cellular senescence to immune checkpoint inhibitor treatment in both the pre-clinical and clinical contexts. Overall, senescence plays a multi-faceted, context-specific role, and has been shown to modulate immune-related adverse event incidence as well as immune checkpoint inhibitor response.

Hyperglycemia has been associated with increased inflammatory indexes and larger infarct sizes in patients with obstructive acute myocardial infarction (obs-AMI). In contrast, no studies have explored these correlations in non-obstructive acute myocardial infarction (MINOCA). We investigated the relationship between hyperglycemia, inflammation and infarct size in a cohort of AMI patients that included MINOCA. Patients with AMI undergoing coronary angiography between 2016 and 2020 were enrolled. The following inflammatory markers were evaluated: C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR). Myocardial infarct size was measured by peak high sensitivity troponin I (Hs-TnI) levels, left-ventricular-end-diastolic-volume (LVEDV) and left ventricular ejection fraction (LVEF). The final study population consisted of 2450 patients with obs-AMI and 239 with MINOCA. Hyperglycemia was more prevalent among obs-AMI cases. In all hyperglycemic patients - obs-AMI and MINOCA - NLR, NPR, and LPR were markedly altered. Hyperglycemic obs-AMI subjects exhibited a higher Hs-TnI, a larger LVEDV and a lower LVEF compared to normoglycemic ones. Conversely, MINOCA patients showed similar myocardial damage, irrespective of glycemia. Our data confirm the association of hyperglycemic obs-AMI with elevated inflammatory markers and larger infarct sizes. MINOCA patients exhibited modest myocardial damage, regardless of admission glucose levels.

In an effectively managed grazing system, goats as grazers can benefit the land's physical, chemical, biological, and economic aspects. However, little research has evaluated rotational and continuous goat grazing in Kentucky. This observational study investigated the impact of rotational and continuous grazing on forage production and goat performance. One group of 10 does was placed on a rotational pasture, and another group of 10 does were placed on a continuous pasture, each pasture measuring two acres. The pastures were side-by-side with similar forage types and compositions. Goat performance was measured by body weight and eye color score (FAMCHA). Forage production was measured weekly by collecting forage heights at three random spots in each pasture. The rotational grazing field displayed a more evenly grazing pattern, while the continuous field experienced overgrazing in some areas and overgrown of the less desired forage. Goats on the continuous field had a decrease in body weight, while the weights were more consistent in the rotational grazing field. The FAMACHA score was temporarily reduced on the rotational grazing pasture, indicating that properly managed rotational grazing may prevent anemia, possibly by reducing the shedding of gastrointestinal parasites. However, due to drought and lack of forage, the FAMACHA score of goats in the rotational grazing system reverted to its original status by the end, indicating that more extensive management and timely adjustments are necessary to ensure optimal goat performance. Our results suggest that rotational grazing may support more consistent forage yields and body weights of goats and has the potential to reduce the incidence of anemia and parasitic infestations in goats in Kentucky.

Emerging evidence suggests that the human vermiform appendix is not a vestigial organ, but rather an immunological organ of biological relevance. It is hypothesised that the appendix acts as a bacterial ‘safe house’ for commensal gut bacteria and facilitates re-inoculation of the colon after disruption through the release of biofilms. To date, no studies have attempted to explore this potential mechanistic function of the appendix. We conducted a pre-post intervention study in adults (n=59) exploring reestablishment of the gut microbiota in those with and without an appendix after colonic disruption via bowel preparation and colonoscopy. Gut microbiota composition was measured one week before and one month after bowel preparation and colonoscopy using 16S rRNA sequencing. We observed between group differences in gut microbiota composition between those with (n=45) and without (n=13) an appendix at baseline. These differences were no longer evident one-month post-procedure, suggesting that this procedure may have ‘reset’ any potential appendix-related differences between groups. Both groups experienced reductions in gut microbiota richness and shifts in beta diversity post-procedure, with greater changes in those without an appendix, and there were five bacterial genera whose re-establishment post-procedure appeared to be moderated by appendicectomy status. This small experimental study provides preliminary evidence of a potential differential reestablishment of the gut microbiota after disruption in those with and without an appendix, warranting further investigation into the potential role of the appendix as a microbial safe house.

Chitin/chitosan and collagen are two of the most important bioactive compounds with applications in the pharmaceutical, veterinary, nutraceutical, cosmetic, biomaterials, and other industries. When extracted from fish and shellfish non-edible parts, by-catches, and invasive species, their use contributes to a more sustainable and circular economy. The present article reviews the scientific knowledge and publication trends along the marine chitin/chitosan and collagen value-chains and assesses how researchers, industry players, and end-users can bridge the gap between scientific understanding and industrial applications. Overall, research on chitin/chitosan remains focused on the compound itself rather than its market applications. Still, chitin/chitosan use is expected to increase in food and biomedical applications, while that of collagen is expected to increase in biomedical, cosmetic, pharmaceutical, and nutritional applications. Sustainable practices, such as the reuse of waste materials, contribute to strengthen both value-chains; the identified weaknesses include the lack of studies considering market trends, social sustainability, and profitability, as well as insufficient examination of intellectual property rights. Government regulations, market demand, consumer preferences, technological advancements, environmental challenges, and legal frameworks play significant roles in shaping both value-chains. Addressing these factors is crucial for seizing opportunities, fostering sustainability, complying with regulations, and maintaining competitiveness in these constantly evolving value-chains.

Obesity is related to the establishment of chronic inflammation and metabolic diseases, but it can be positively influenced by the regular practice of physical activity. The study aimed to compare the anthropometric, metabolic, and inflammatory parameters of physically active Military Police Officers (MPOs) with those who are less physically active. Sixty male MPOs, low activity (n=28) and physically active (n=32) participated. The following parameters were measured: plasma cytokine levels, C-reactive protein (CRP) levels, circulating glucose triglyceride (TAG) and high-density lipoprotein cholesterol (HDL-C) levels, and plasma glutamic oxalacetate transaminase (GOT), glutamic-pyruvate transaminase (GPT), and gamma-glutamyl transferase (GGT) activities. The physically active group presented lower body fat and reduced TAG and IL-8 levels compared to the low activity group. Moreover, a negative correlation between SPE and SBP, DBP, BPM was detected for the physically active group (p<0.05) but not in the low activity group. Furthermore, the physically active group's work time (WT) values were not correlated with the important metabolic markers SBP, DBP, BPM, GLU, TAG (p>0.05) but could be in the low activity group (p<0.05). These findings highlight the fundamental protective role of physical activity in controlling body composition, subclinical inflammation, and cardiovascular risk in MPOs.

Zingiber officinale rhizome is widely cultivated in the central region of Sudan (Gezira) and data on the biological properties of this variety grown in the Sudan climate is scarce. The study aims to comprehensively analyze the antibacterial, antioxidant, phytochemical, and GC-MS properties of Zingiber officinale (Ginger rhizome) to explore its potential applications. The in vitro antibacterial assessment of the aqueous extract of the Sudanese ginger revealed moderate activity against Staphylococcus aureus, Salmonella typhi, Pseudomonas aeruginosa, Escherichia coli , and Klebsiella pneumonia, as resulted from the disc-diffusion which ranged between 12.87±0.11 mm to 14.5±0.12 mm at 30 µg/disc. The minimum inhibition concentration ranged between 6.25 to 25 µg/ml, the MBC were between 25 and 50 µg/ml, and the MBC/MIC exhibited its bactericidal effect against all tested bacteria. The phytochemical screening revealed the presence of various chemical constituents such as saponins, flavonoids, glycosides, alkaloids, steroids, terpenoids, and absence of tannins in the Sudanese ginger rhizome. Furthermore, the GC-MS study of ginger rhizome identified 22 chemical compounds with retention times ranging from 7.564 to 17.023 minutes. The identification of 22 chemical compounds through GC-MS analysis further underscores the prospect of harnessing ginger rhizome for the development of novel medications. The computational analyses showed that ginger compounds bind the 1JIJ and 2QZW with high binding affinities, which reach –9.5 kcal/mol. Ginger compounds also established promising molecular interactions with some key residues, that satisfactorily explain the in vitro results and support the pharmacokinetic and experimental findings. This study lays the groundwork for future research and pharmaceutical exploration aimed at harnessing the beneficial properties of ginger rhizome for medicinal and therapeutic purposes, particularly its antimicrobial potential.

Background Indicators to evaluate progress towards timely access to safe surgical, anaesthesia, and obstetric (SAO) care were proposed in 2015 by the Lancet Commission on Global Surgery. Despite being rapidly taken up by practitioners, datapoints from which to derive them were not defined, limiting comparability across time or settings. We convened global experts to evaluate and explicitly define - for the first time - the indicators to improve comparability and support achievement of 2030 goals to improve access to safe affordable surgical and anaesthesia care. Methods and findings The Utstein process for developing and reporting guidelines through a consensus building process was followed. In-person discussions at a two day meeting were followed by an iterative process conducted by email and virtual group meetings until consensus was reached. Participants consisted of experts in surgery, anaesthesia, and obstetric care, data science, and health indicators from high, middle, and low income countries. Considering each of the six indicators in turn, we refined overarching descriptions and agreed upon data points needed for construction of each indicator at current time (basic data points), and as each evolves over 2-5 (intermediate) and >5 year (full) timeframes. We removed one of the original six indicators (one of two financial risk protection indicators was eliminated) and refined descriptions and defined data points required to construct the 5 remaining indicators: geospatial access, workforce, surgical volume, perioperative mortality, and catastrophic expenditure. Conclusions To track global progress toward timely access to quality SAO care, these indicators – at the basic level - should be implemented universally. Intermediate and full evolutions will assist in developing national surgical plans, and collecting data for research studies.

Orbit and clock products are used in real-time GNSS precise point positioning without knowing their quality. This study develops a new approach to detect orbit and clock errors through comparing geometry-free and geometry-based wide-lane ambiguities in PPP model. The reparameterization and estimation procedures of the geometry-free and geometry-based ambiguities are described in detail. The effects of orbit and clock errors on ambiguities are given in analytical expressions. The numerical similarity and differences of geometry-free and geometry-based wide-lane ambiguities are analyzed using different orbit and clock products. Furthermore, two types of typical errors in orbit and clock are simulated and their effects on wide-lane ambiguities are numerically produced and analyzed. The contribution discloses that the geometry-free and geometry-based wide-lane ambiguities are equivalent in terms of their formal errors. Although they are very close in terms of their estimates when the used orbit and clock for geometry-based ambiguities are precise enough, they are not the same, in particular, in the case that the used orbit and clock, as a combination, contain significant errors. It is discovered that the discrepancies of geometry-free and geometry-based wide-lane ambiguities are coincided with the actual time-variant errors in the used orbit and clock at the line-of-sight direction. This provides a quality index for real-time users to detect the errors in real-time orbit and clock products, which potentially improves the accuracy of positioning.

Artic root is a well-known plant adaptogen with multipotential pharmacological properties. Thin-layer chromatography (TLC) – screening followed by diode-array high-performance liquid chromatography and nuclear magnetic resonance spectroscopy proved to be a reliable and convenient method for simultaneous determination of quality of various herbal raw materials and supplements. This combination allowed for comparing and differentiating arctic root samples as well as defining their authenticity. The study provided information on the chemical and biological properties of the seven chosen samples as well as qualitative and quantitative evaluation of the quality markers: rosavin, salidroside, and p-tyrosol. The absence of rosavin, salidroside, and p-tyrosol in three samples was detected using TLC-screening and confirmed by HPLC-DAD and NMR. The paper highlighted the importance of quality control and strict regulation for herbal medicine supplements and preparations.

This study describes the design and development of novel compounds aimed at optimizing the function of microtubules and tubulin in the immune system and the brain as they relate to the Orch OR theory of consciousness. These compounds are defined by the following molecular formulas:C65H100CoN15O22P(C6H12O5);C65H100CoN15O22P(C5H10NO4);(C65H100CoN15O22P)(C6H12N2O)n;(C65H100CoN15O22P)(C6H12O5)(C6H12N2O)n;(C6H12N2O)n(C6H12O5)m;Zn(C6H12O5)2;These molecules, formulated under the form of drugs, health functional foods, or food supplements, have the potential to positively affect a number of areas ranging from prevention and therapy of neurological diseases to supporting the immune system.

The structures of a number of dimers of sulphur dioxide and ozone have been optimized by means of a series of ab initio calculations. The dimer species have been classified as either genuine energy minima or transition states of first or higher order, and the most probable structures consistent with the experimental data have been confirmed. The molecular orbitals engaged in the interactions resulting in adduct formation have been identified and relations between the orbitals of the dimers of the valence isoelectronic monomer species examined. The vibrational spectra of the most probable structures have been computed, and compared with those reported in the literature, particularly with spectra observed in cryogenic matrices. The calculations have been extended to predict the properties of a number of possible heterodimers formed between sulphur dioxide and ozone.

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target. Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection. Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

The present reality about the Nigerian economy calls for investment and development in the non-oil sector. This becomes necessary as a result of fall in the oil price in the global market. This paper examined the Bayesian Vector Autoregression (BVAR) modeling and forecasting of the dynamic interrelationship between Economic growth and revenue from the oil and non-oil sectors in Nigeria. To achieve this, annual data on Gross Domestic Product (GDP), revenue from oil and non-oil sectors were collected from Central Bank of Nigeria (CBN) bulletin, the sample from 1981 to 2008 was used for analysis, while sample from 2009 to 2014 was used for model validation. Six (6) versions of Sims-Zha BVAR models were compared for out-of-sample forecast, the result revealed the superiority of the BVAR6 model over the other BVAR models. Lastly, evidence from the decomposition forecast errors revealed that revenue of oil sector contributed 7.69% to GDP while revenue from non-oil sector contributed 0.12% to GDP in Nigeria. This paper therefore recommended that the present government should encourage investment that is geared toward development in the non-oil sector, of which it has the capacity to improve the Economic growth of the Nigerian economy.

Acid stress poses a common challenge for bacteria in diverse environments by the presence of inorganic (e.g., mammals’ stomach) or organic acids (e.g., feed additives; acid-based disinfectants). Limited knowledge exists regarding acid-tolerant strains of specific serotypes, clonal lineages, or sources in human/animal pathogens, namely non-typhoidal Salmonella enterica (NTS) and Enterococcus faecium (Efm). This study evaluated acidic pH and peracetic acid (PAA) susceptibility of Efm (n=72) and NTS (n=60) from diverse epidemiological/genetic backgrounds, and with multiple antibiotic resistance profiles. Efm minimum growth/survival-pH was 4,5-5/3-4 and for NTS 4,0-4,5/3,5-4,0. Among Efm, only those of clade-non-A1 (non-hospital associated) or food chain demonstrated greater tolerance to acidic pH compared to clade-A1 (hospital-associated clones) or clinical isolates (P<0.05). MDR (multidrug-resistant) NTS survived better to acidic pH (P<0.05). The MICPAA/MBCPAA was 70-120/80-150mg/L for Efm and 50-70/60-100mg/L for NTS. Efm-clade-A1 or MDR strains exhibited higher PAA tolerance than clade-non-A1 or non-MDR ones (P<0.05). Higher tolerance was found in non-MDR and clinical NTS than in food chain isolates (P<0.05), but not between different serogroups. This unique study identifies specific NTS or Efm populations more tolerant to acidic pH or PAA, emphasizing the need for further research to tailor control measures of public health and food safety within a One Health framework.

Background: Poisoning constitutes an important part of morbidity and mortality among environmental emergencies that can be prevented, frequent in childhood, requiring rapid diagnosis and treatment. This study aimed was to examine the epidemiological, clinical and therapeutic characteristics of drug and corrosive poisonings in terms of children. Materials and Methods: Between January 2010 and December 2018, 1678 patients between the ages of 1-16 who applied to the emergency department with drug and corrosive poisoning were included in the study. The patients were divided into three groups as 1-5, 6-11 and over 12 years of age, and the substances with known pharmacological agents were divided into 10 groups. The Zargar Classification (7) was used to determine the degree of damage caused by corrosive substances in the esophagus. Results: The mean age of the patients was 8.32 ± 3.23 years (1-15 years). The girl/boy ratio of the cases was 1.18 / 1 and 54.3% were girls. 18.9% of the cases were under five years of age, 61% were between 6-11 years and 20% were older than 12 years. 94.6% of the patients were poisoned by drugs and 5.4% of them were poisoned due to non-drug reasons. Accidental poisoning was most commonly seen in children aged 6-11 and suicides were seen in children older than 12 years. It was found that 62.2% of the poisonings were accidental and 37.8% were suicidal. The most common causes of poisoning were analgesics and paracetamol exposure as a pharmacological agent. Mortality was found to be most common in 1-5 years age group and accidental poisonings. Accidental poisoning was common in girls and suicidal poisoning was common in boys. Grade 3 damage was found endoscopically in all of the mortalities due to corrosive substances. Conclusion: It was found that accidental poisoning was observed in children under five years of age, suicides were observed in children older than 12 years and the most important cause of mortality was due to corrosive substances. Cause-specific rapid diagnosis and treatment will contribute to the reduction of morbidity and mortality.

There is a perception among the inhabitants of the Aburrá Valley Region, that this heavily populated region, situated in the Andean mountains of Colombia, has been suffering large temperature elevations in the last years, especially in the last decade. To give perspective about this issue, the authors have gone through the available information about temperature changes in three meteorological stations in the region and have correlated it with a set of variables of urban, climatic and energetic nature, with the intention of developing an approximate model to understand the temperature changes. Changes in the mean temperature, based on the linear correlation of the data were estimated on 0.47oC for the 20 years between 1995 and 2015; the study showed that 60% of change was found to be related to local human activities and 40% was attributed to the impact of global warming. For the local influences some practical mitigation actions are proposed, related to improve the energy management and paying more attention to the temperature changes trough improvements in the number and capability of sampling stations in the urban air and in the river, which serve as clear indicators of the changes and the effect of any mitigation measures.

There is a perception among the inhabitants of the Aburrá Valley Region, that this heavily populated region, situated in the Andean mountains of Colombia, has been suffering large temperature raises in the last years, especially in the last decade. To give perspective about this issue, the authors have gone through the available information about temperature changes in three meteorological stations in the region and have correlated it with a set of variables of urban, climatic and energetic nature, with the intention of developing an approximate model to understand the temperature changes. Changes in the mean temperature, based on the linear tendencies, were estimated on 0.47ºC for the 20 years between 1995 and 2015; 60% of change was found to be related to local human activities and 40% was attributed to the impact of global warming.

Eucalyptus, a therapeutic plant mentioned in the ancient Algerian pharmacopeia, specifically two species belonging to the Myrtaceae family - E. radiata and E. cinerea, were investigated in this study for their antibacterial, antioxidant, and anti-inflammatory properties. The study used aqueous extracts (AE) obtained from these plants, and the extraction yields were found to be dif-ferent. The in vitro antibacterial activity was evaluated using a disc diffusion assay against three typical bacterial strains. The results showed that E. radiata EAq was effective against all three strains, while E. cinerea EAq was only effective against E. coli. Both extracts displayed significant antioxidant activity compared to BHT. The anti-inflammatory impact was evaluated using a pro-tein (BSA) inhibition denaturation test. The E. radiata extract was found to inhibit inflammation by 75% at a concentration of 250 g/ml, significantly higher than the placebo. Ellagic acid, a pri-mary phytochemical found in the extracts, demonstrated noteworthy toxic and pharmacokinetic characteristics and a maximum binding energy of -7.53 kcal/mol for its anti-TyrRS activity in sili-co. The study suggests that the extracts and their primary phytochemicals could enhance the effi-cacy of antibiotics, antioxidants, and non-steroidal anti-inflammatory drugs (NSAIDs). As phar-maceutical engineering experts, we believe this research contributes to developing natural-based drugs with potential therapeutic benefits.

Sperm during the freezing and thawing process is damaged by oxidative stress. Thus, its antioxidant scavenger is essential for sperm survival and death in frozen-thawed semen. We used melatonin and silymarin in experiments. Our study aimed to identify the effect of melatonin and silymarin on the motility and viability of sperm, reactive oxygen species (ROS), and nitric oxide (NO) production in frozen-thawed boar semen. Melatonin and silymarin were treated alone and co-treated in the fresh boar semen. Boar semen was collected using the gloved-hand method from ten crossbred pigs, and the age of the experimental ten male pigs was 28.7 ± 3.2 months. We evaluated sperm viability using SYBR-14 and PI kit, and ROS and NO production were detected by DCF-DA and DAF-2, respectively. The sperm motility was not significantly different between non-treatment and treatment. ROS and NO production in frozen-thawed sperm were decreased by melatonin and silymarin (P < 0.05). Moreover, silymarin significantly reduced NO production more than melatonin (P < 0.05). Melatonin (46.37 ± 1.10) and silymarin (46.13 ± 0.80) enhanced the viability of sperm (P < 0.05). We suggest that melatonin and silymarin are essential antioxidants in semen cryopreservation for protecting sperm damage and maintaining sperm viability. Melatonin and silymarin may be useful antioxidants in freezing boar sperm.

This work addresses the problem of automatic head pose estimation and its application in 3D gaze estimation using low quality RGB--D sensors without any subject cooperation or manual intervention. The previous works on 3D head pose estimation using RGB--D sensors require either an offline step for supervised learning or 3D head model construction which may require manual intervention or subject cooperation for complete head model reconstruction. In this paper, we propose a 3D pose estimator based on low quality depth data, which is not limited by any of the aforementioned steps. Instead, the proposed technique relies on modeling the subject's face in 3--D rather than the complete head, which in turn, relaxes all of the constraints with the previous works. The proposed method is robust, highly accurate and fully automatic. Moreover, it does not need any offline step. Unlike some of the previous works, the method only uses depth data for pose estimation. The experimental results on the Biwi head pose database confirm the efficiency of our algorithm in handling large pose variations and partial occlusion. We also evaluate the performance of our algorithm on IDIAP database for 3D head pose and eye gaze estimation.

Foliage-feeding fall armyworm (Spodoptera frugiperda) and root-feeding western corn rootworm (Diabrotica virgifera virgifera) are maize (Zea mays L.) pests that cause significant yield losses. Jasmonic acid (JA) play pivotal defense role against insects. 12-oxo-phytodienoic acid (12-OPDA) is converted into JA by peroxisome-localized OPDA reductases (OPR). However, little is known about the physiological functions of cytoplasmic OPRs. Here, we show that disruption of ZmOPR2 reduced wound-induced JA production and defense against FAW while accumulating more JA catabolites. Overexpression of ZmOPR2 in Arabidopsis enhanced JA production and defense against beet armyworm (Spodoptera exigua). In addition, lox10opr2 double mutants were more susceptible than either single mutant, suggesting that ZmOPR2 and ZmLOX10 uniquely and additively contributed to defense. In contrast to the defensive role of ZmOPR2 and ZmLOX10 in leaves, single mutants did not display any alteration in root herbivory defense against WCR. Feeding on lox10opr2 double mutants resulted in increased WCR mortality associated with greater herbivory-induced production of insecticidal death acids and ketols. Thus, ZmOPR2 and ZmLOX10 cooperatively inhibit synthesis of these metabolites during herbivory by WCR. We conclude that ZmOPR2 and ZmLOX10 regulate JA-mediated resistance in leaves against FAW while suppressing insecticidal oxylipin synthesis in roots during WCR infestation.

Oil and gas pipeline vandalism is a recurrent problem in oil rich zones of Nigeria and its West African neighbors and remains a challenge for multinationals to set ahead control measures to avert possible damages to operations both in infrastructure and business profit margins. In this paper, an integrative systems model comprising of a machine intelligence technique called Hierarchical Temporal Memory (HTM) and a sequence learning neural network called the Online-Sequential Extreme Learning Machine (OS-ELM) is proposed for monitoring and prediction of pipeline pressure data. The system models the continual prediction of pipeline oil/gas pressure signals useful for secure monitoring and control to avert acts of vandalism in oil and gas installations. The HTM uses a spatial pooler operated in temporal aggregated fashion and is defined as HTM-SP. The OS-ELM technique uses an explicit hierarchical training scheme so that the best cost estimates may be found after a stipulated number of trial runs. We study the performance of three OS-ELM neural activations: the sigmoid (sig), sinusoidal (sin) and radial basis function (rbf) activations. The results indicate improvement factors of 1.297, 1.297 and 1.300 of the HTM-SP over the OS-ELM sigmoid, sinusoidal and radial basis activations respectively.

Climate change-induced Sea level rise, shoreline changes, and coastal erosion are projected to drive massive population displacement and mobility in Africa. This study was conducted to examine the pattern of shoreline changes, coastal erosion, land use/Land cover dynamics their projections, and its implications on internal migration in Senegal, Kenya and Tanzania representing West and East Africa. The digitized shoreline was mapped into both erosion, accretion and trend analysis which further explains the vulnerability and physical processes that could trigger human displacement within the context of environmental/climate migration. Analysis of landuse and land cover dynamics was obtained from Landsat 5 TM of 1986, Landsat 7 ET of 2006, Landsat 8 OLI/TIRS of 2016 and Landsat 9 OLI/TIRS 2022 and computed using ArcGIS 10.7 for Land-use change and percentage change in square kilometers was conducted to examine landuse/landcover dynamics and their contributions to the risk of coastal erosion in the study regions. The outcome of the shoreline analysis reveals that 972.03sqkm of land has been lost to coastal erosion in Senegal from 1986-2022 with 2016-2022 described as the period with the highest in terms of land loss. In Kenya, -463.30sqkm of land has also been lost to coastal erosion and agents of wave processes with 1986-2006 recording the highest share of -87.74% loss of valuable land while In Tanzania, -1033.35sqkm of valuable land has been lost from 1986-2022 to coastal erosion with 2006-2016 alone recording -10.4634% of land loss. The result of the land use/land cover percentage change analysis indicates a massive loss of vegetation cover with a significant increase in settlement representing urbanization. The scenario modeling of the shoreline on 10,20 and 30ms indicates that 567 persons per sq, 25904.5 persons per sqm and 25904.5 persons per sq km for both 20 and 30ms will be displaced in Senegal while in Kenya 577.5 persons per sq km will be displaced at 10m followed by 1210.3 persons per sq km at 20m and 7737.3 sq km at 30m. In, Tanzania, 702001.9 persons per sq km are projected to be displaced at 10m shift in the shoreline. Structured Questionnaires were administered to elicit responses from coastal dwellers on their perception of coastal erosion and environmental migration as part of ground truthing and the result of the survey affirms that coastal erosion and its exposure are the major drivers of environmental migration in the study area.

For decades, the discoverability and visibility of a paper relied on the readership of the academic journal where the publication was issued. The public's increasing interest in scientific research, particularly in biomedicine, has led news media outlets to play a significant role in disseminating scientific advances. This investigation, which explores the potential impact of news media stories on the citations and altmetrics of a paper, was conducted with thoroughness and rigour. A total of 2020 open access biomedical research papers, all published in the same year, 2015, and in journals with an impact factor between 10 and 14, were investigated. The papers were split into two groups based on the sole criterion of receiving or not receiving news media coverage. Papers with news media coverage accounted for 44% of the total. They received, on average, 60% more citations, 104% more blogs, 150% more X posts, 106% more Facebook reports, 40% more Wikipedia references, 85% more videos, and 51% more Mendeley readers than papers without news media coverage. The correlation between news media outlets and increased citations and altmetrics is evident. However, the broader societal impact of news media coverage, in terms of bringing scientific matters or discoveries to the public eye, appears to be more robust when compared to the reactions of the scientific community.

Background and objectives: Patients with multiple sclerosis (MS) have many potential factors (spasticity, immobilization, glucocorticoids use) which can deteriorate the anthropometrical status and body composition and may have the potential impact on the functional mobility and basic motor skills improvement after physiotherapy. The aim of the study was to assess the functional mobility and basic motor skills in patients with MS and to correlate them with disability and anthropometrical status and body composition parameters. Materials and Methods: Timed Up-and-Go test (TUG), and six-minute walk test (6MWT) were performed in 36 patients with MS before and after 4 weeks of physiotherapy. Body mass index (BMI), waist to height ratio (W/HtR), and waist-to-hip ratio (WHR) were assessed in this group. Body composition was evaluated by bioelectrical impedance analysis (BIA) and fat mass (FAT), fat free mass (FFM), total body water (TBW) and predicted muscle mass (PMM) were expressed as percentage of body mass. Clinical status was assessed by EDSS and AI scales. Results: After physiotherapy, there was a significant improvement in functional mobility and basic motor skills assessed by total distance in 6MWT (p<0.001) and in TUG trials (p<0.001). Positive significant correlations were found between the results obtained in both tests (either before and after physiotherapy) vs. FFM, TBW and PMM, whilst worse results in functional mobility and basic motor skills correlated significantly with higher WHtR, WHR and FAT (p<0.05). Clinical status (EDSS) were significantly related to the WHtR and body composition parameters with the same manner as the results in the either 6MWT and TUG. However, there were no significant relationships between BMI vs. either clinical status (EDSS, AI) and functional mobility tests results in patients with MS. Conclusions: Functional mobility and basic motor skills may be significantly improved during the physiotherapy, but they are related to the anthropometrical status and body composition of MS patients. Moreover, disability status is also significantly related to this parameters. Body composition deterioration seems to be the important target for the therapeutic intervention in MS patients. For proper nutritional status assessment in patients with MS, body composition analysis or WHtR instead BMI should to be used.

In the context of global warming and reduction in fresh water availability is presented a study of the evolution of dew, rain and evapotranspiration in the NW of Africa. The time periods are concerned with the years 2005-2020, using existing data, and years 2020-2100, using the low and high emissions representative concentration pathway scenarios RCP 2.6/8.5 from the Cordex database. A continuous decrease in rain precipitation is observed, on order of -14 mm/decade for the more credible scenario RCP 8.5. The amplitude is maximum on the coast and on the foothills of Atlas. A clear decrease in dew yields is also observed along a NW/SE axis, strongly correlated with a corresponding decrease in relative humidity (up to 7%). Chemical dew and rain data in the representative site of Mirleft correspond to the major cations Na+ > Ca2+ > Mg2+ > K+, similar to a local spring water. Concentrations in rain are about two times less than in dew water. Ionic concentrations are compatible with WHO standards. The seasonal variations of the ionic concentrations in dew and rain follow a volume dilution dependence. The expected diminution in dew and rain volumes according to the RCPs 2.6 and 8.5 should increase the dew and rain ionic concentrations in the future.

This paper gives solutions to puzzles of double Wheeler’s delayed choice experiments, a photon’s passing two paths simultaneously and wave collapse velocity measure, and shows new quantum control, new quantum oscillation and new controlling photon oscillator (that can be arranged in quantum computer and quantum network as their classical correspondences) in experiments. Furthermore, this paper obtains the measured attractive state and the new useful key technology of altering state’s evolving paths for quantum systems. We discover the reason and the technological way for the present changes the past, further show their feasible experiments of new quantum control, new quantum oscillation and new quantum oscillator. Finally, this paper achieves the collapse response time t of wave, further concretely deduces the measured collapse velocity of quantum system. In the past, the collapse velocity cannot be objectively deduced and experimentally measured.

Myeloid neoplasms and acute leukemias include different entities that have been recently re-classify taking into account molecular and clinicopathological features. The myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) category comprises a heterogeneous group of hybrid neoplastic myeloid diseases characterized by the co-occurrence of clinical and pathologic features of both myelodysplastic and myeloproliferative neoplasms. The most frequent entity in this category is chronic myelomonocytic leukemia (CMML) which is, after acute myeloid leukemia (AML), the main myeloid disorder prone to develop cutaneous manifestations. Skin lesions associated with myelodysplastic and myeloproliferative neoplasms include a broad clinical, histopathological and molecular spectrum of lesions, poorly understood and without a clear-cut classification in the current medical literature. The aim of this review is to describe and classify the main clinical, histopathological and molecular patterns of cutaneous lesions in the setting of MDS/MPN in order to improve the diagnostic skills of dermatologists, hematologist and pathologist who deal with these patients.

The study was carried out in zone 7 of Ecuador, in ecosystems of the Southern Montane Evergreen Forest of the Eastern Cordillera of the Andes that goes from 2200 to 3000 masl. In the Evergreen Seasonal Lower Montane Forest of Catamayo-Alamor, which ranges from 1600-2000 meters above sea level and finally in the Semideciduous Foot Montane Forest of Catamayo-Alamor, which ranges from 400-1600 meters above sea level. The objective was to know the occurrence, structure and abundance of J. neotropica. The investigation consisted of collecting secondary information on the occurrence of the species, to later verify it in situ. Six sites with areas ≥ 0.5 hectares were identified, four in the province of Loja and two in the province of Zamora Chinchipe. Regarding the structure, it was determined that there are significant statistical differences as well as in the dasometric variables between one site and another, presenting better growths El Tundo with average values in DAP(cm)= 45.16; G(m2) = 1.41; HT(m)= 19.22; HC(m)= 13; VC(m3) = 3.55; VT(m3) = 5.22. Regarding the Morisita index, the species presents adistribution pattern &gt;1. Regarding abundance, it was determined that Algeria presented a maximum of 297 (ind/ha), and La Victoria 46 (ind/ha) with a minimum.

The changing epidemiology of Staphylococcus aureus has created several gaps in its population structure and emergence of strains. Two global shifts in the aftermath of the past methicil-lin-resistant S. aureus (MRSA) pandemic are: a rise in healthcare-associated infections and evolu-tion of cutaneous and soft tissue infections with high morbidities and mortalities. Furthermore, bitter lessons from COVID-19 showed S. aureus necrotizing-pneumonia and skin conditions ag-gravating Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Monkeypox manifestations. Limited data and paucity of high-quality evidence exist for many key clinical questions. Using clinical microbiology, molecular characterization, hospital data on age and in-fection sites, and antibiograms, we have investigated S. aureus infection patterns. We showed that age-specific distribution in both intensive care unit (ICU) and non-ICU revealed highest infection rates (94.7%) in senior-patients >50 years; most were MRSA (81.99%). However, specific distribu-tions of geriatric MRSA and MSSA rates were 46.5% and 4.6% in ICU and 35.48% and 8.065% in non-ICU, respectively. Intriguingly, age groups 0-20 years showed uniquely similar MRSA pat-terns in ICU and non-ICU patients (13.9%, 9.7%, respectively) and MSSA in ICU (11.6%). In age groups 20-50 years, MRSA were 2-fold in non-ICU (35%) than ICU (18.6%). Interestingly, highly significant association was found between infection-site and age-groups (P-value .000). Skin in-fections remained higher in all ages; pediatrics 32.14%, adults 56%, and seniors 25% while res-piratory infections were lower in pediatrics (14.3%) and adult 17%), and highest in seniors (38%). Blood and “other” sites in pediatrics recorded (28.6%; 25%, respectively), slightly lower in adults (18.6%; 8.6%) and seniors (14%); 22.8%), respectively. Further, significant association existed between infection-site and MRSA (Chi-Square Test, P-value .002). The common cutaneous infec-tions across all age-groups and the significant association of MRSA to geriatric-respiratory infec-tions have a high potential for skin-carriage as reservoir for endogenous infection. The similar frequencies of both lineages in youth in all settings imply MSSA-carriage as potential evolutionary origins for MRSA. These findings have important clinical implications for strategic planning in patient management and S. aureus control particularly in age-specific infections and vigilance for potential viral coinfections.

Licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata. CRC treatment has always been challenged by the development of resistance. We investigated the antiproliferative activity of LCH in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells. We found that LCH decreased epidermal growth factor receptor (EGFR) and AKT kinase activities and related activating signaling proteins including phospho (p)-EGFR and pAKT. A computational docking model indicated that LCH may interact with EGFR, AKT1, and AKT2 at the ATP-binding sites. LCH induced ROS generation, as verified by N-acetyl-L-cysteine (NAC) treatment, and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP and increased. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of subG1 cells and arrested the cell cycle at the G1 phase. LCH inhibits the growth of Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, and inducing ROS generation and ER stress-mediated apoptosis. Therefore, LCH could be a potential therapeutic agent for improving not only Ox-sensitive but also Ox-resistant CRC treatment.

As global economic integration and rapid technological advancements transform international business, international engineering contracting has become essential for achieving sustainable development goals (SDGs). This paper investigates the significant impact of China’s strategic initiatives, notably the "Going Global" strategy and the Belt and Road Initiative (BRI), on the operational practices of Chinese enterprises involved in overseas investments. Central to this transformation is the Engineering, Procurement, and Construction (EPC) model, which emphasizes the integration of supply chain management and stakeholder collaboration to enhance performance in international EPC projects and underscores the crucial role of these elements in promoting sustainability. Incorporating insights from social network data analysis, this study reveals that contractors collaborating with various stakeholders—such as owners/consulting engineers, domestic and foreign customs departments, and group headquarters/design parties—exhibit a high degree of similarity in personnel profiles. This suggests that the internal organizational structure and personnel allocation of contractors could be optimized to enhance operational efficiency, aligning with the collaborative patterns identified. This study addresses a critical research gap by exploring how effective supply chain management and collaborative stakeholder engagement within multinational EPC projects contribute to sustainable outcomes. Employing advanced social network analysis software, the research examines the complex interactions among stakeholders and their influence on procurement dynamics. Findings indicate that strong relational networks and strategic collaborations significantly enhance procurement efficiency and project success, underscoring the importance of supply chain integration. Ultimately, integrating supply chain management principles into the EPC model not only offers innovative perspectives for advancing sustainability in international projects but also provides actionable insights for improving project outcomes within the BRI framework. This research underscores the pivotal role of supply chain organization and stakeholder cooperation in achieving sustainability objectives, thereby enriching the discourse on sustainable enterprise operation and supply chain management in the context of global initiatives.

This study aims to get growth and feed efficiency of Nile tilapia (Oreochromis niloticus) with plant oils supplement from paring coconut (P.C.) and candlenut (C.N.) enrichment of Se in rations formula. The oil of P.C. was dominated by saturated fatty acid (SFA) lauric (42.67%), while the extract of C.N. was unsaturated fatty acids (UFA), linoleic (34.4%), and oleic (48.99%). The extract of P.C. and C.N. or mix oils added 4% in basal ration formula (28% crude protein (C.P.) with energy-protein ratio 8 kcal/kg). Completely Randomized Design (6 × 3) consists R1: basal ration; R2: basal formula with blend of paring coconut and candlenut oils (2% PC + 2% CN); R3: blend oils (R2) with trace additive Se; R4: 4% PC + Se; R5: 4% CN + Se; R6: control ration (32% CP). The result of production parameters showed that blend oils supplement enrichment Se 0.15 ppm in feed formula with ratio SFA: UFA = 1: 1 was the best growth rate equal with high protein feed. Feed efficiency ranged from 50.14-57.93% and protein efficiency ratio 1.72-2.06 both for CN oil (SFA: UFA = 1 : 2), paring coconut (SFA : UFA = 2 : 1) or blend oils (SFA : UFA = 1 : 1). Incorporation of blend oils with Se can be used for Nile tilapia fingerlings (≥ 10 g). Paring coconut oil was trend increasing on feed efficiency for tilapia bigger stadium (≥ 30 g).

The aims of this study were: (1) to analyze the level of agreement of a sample of Italian people with the rights of people with physical and psychical disabilities (PwPHDs and PwPSYDs) to have satisfying sexuality, to marry, to adopt a child; (2) to inquire if PwPSYDs were subject to less recognition than PwPHDs; (3) to verify if socio-demographic characteristics, such as age, sex, education, occupation, geographical origin, relational status, sexual orientation, and religiosity, associated with being against these sexual and parenting rights (SPRs). An online anonymous questionnaire inquired the level of agreement or disagreement with statements regarding the SPRs of PwPHDs and PwPSYDs. 973 participants, aged 18 – 84 years (71.1% females) were considered for analyses; At least 7 out of 10 participants declared in favor of the SPRs of PwPHDs, while the SPRs of PwPSYDs were always subjected to higher underrecognition. Religiosity almost invariably associated to being against the SPRs of PwDs. Being male, of higher age and lower education also associated with lower recognition. A better identification of the less tolerant respondents and of the less recognized categories may allow for specific strategies for promoting the recognition of the SPRs for PwDs.

The severe acquired respiratory coronavirus–2 (SARS–CoV-2) infection has initiated both acute and chronic COVID–19 disease between 2020 and 2023, currently evolving with other homologous prior coronavirus strains of the Nidoviridae order, which encompasses other prevalent alpha/ beta coronaviruses, but also the Middle East Respiratory Syndrome (MERS-CoV) and SARS-CoV-1, with recent SARS–CoV–2 variants, increasing demands for effective immunogens and therapeutic approaches that will reduce global disease burden and further infection from SARS–CoV-2 affected individuals that may experience post acute sequelae (PASC) or “Long COVID”. Following a worldwide programme of prophylactic vaccination, there is still a dilemma in the efforts to find prophylactic and early therapeutic approaches that would treat novel SARS-CoV-2 variants and prevent future epidemics or pandemics within host human and animal populations, where zoonotic or cross species transfer naturally occurs. Concerns about viral immune escape intersect at a specific point; a gained evolutionary ability of several viruses to co–infect and compete against previous scientific advances since 1796 that remain undetected or asymptomatic during the early stages of infection progressing to symptomatic and severe disease via the double methylation of the 5' end of eukaryotic DNA or RNA-based viral genomes, the 7-MeGpppA2’-O-Me cap, and its double methylation capping process is performed by the activated viral 2’ - O - Methyltransferase (MTase) enzyme, a complex of two viral non-structural proteins (NSPs) joined together through an activation process (NSP10/16) and by N7-Methyltransferase (N7-MTase/NSP14), respectively. Moreover, it was discovered that polymorphic viruses translate NSP1, which prevents the activation of various Pattern Recognition Receptors (PRRs), and consequently, detection of Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs) alike. NSP1 also silences important interferon-encoding genes (INGs) and interferon-stimulated genes (ISGs), is signalled in a paracrine manner to neighbouring cells, and that induces the apoptosis of host cells, inducing an effect of “trace erase” effect and making the viral infection as immunologically “invisible” as possible during the initial, key stages of viral replication and distribution, all such mechanisms occurring independently of the viruses in cause. Another important viral NSP is NSP14, as it plays two functional roles that are independent of each other; to produce new viral genetic material for the purpose of maintaining the validity of the viral genome as well, and not just transfer a methyl group to the 5’ end of the viral genome. Other viral NSPs share a role with NSP1, 10, 14 and 16 in directly suppressing the activation of PRRs and ISGs, and all such viral proteins help the virus in its process of self-camouflaging against first- and second-line immunity, thereby often severely impacting the quality of the produced adaptive immune responses. The outcome of all such phenomena is the sharp decrease in the host Type I and Type III interferons' (IFNs) rate of synthesis by the host cells, that would usually occur and affect homeostatic cellular pathways, resulting in further viral replication and induced apoptosis. Nonetheless, effects of microbial immune evasion during the development of other viral or carcinogenic pathologies are not widely known. In short, polymorphic viruses developed a proportionate evolutionary response against developed adaptive immune responses, by currently relying on gaps mostly situated in the natural immune system in their process of molecular self-camouflaging. Scientists developed numerous approaches of early treatment that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration whilst filtering for the most appropriate solutions. For example, the administration of recombinant human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can simulate intracellular infection and stimulate cellular activity in a timely manner, training the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Another example could involve the treatment of natural and adaptive lymphocytes with a low dose of IFNs I and possibly III, prior to their insertion into the host lymphatic system, possibly alongside additional recruitment of plasmacytoid dendritic cells (pDCs) as further interferon “factories”, all with the purpose of early infection management. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. It is until the scientific community realises this potentially crucial aspect that large proportions of the world population will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently, monkeypox and possibly avian flu. Of note, it has been indicated that IFN I and / or III display significant immunising, early therapeutic and clinical disease onset-attenuating effects for many other microbial evoked diseases, as well as for a number of oncological diseases.

We report a detailed investigation of vibrational modes, structure, and dynamics of glutathione (GSH) solutions using ultrasonic relaxation spectroscopy, FT-IR vibrational spectroscopy and electronic absorption measurements. The experimental data were analyzed in view of density functional theory (DFT) and molecular docking calculations. Three distinct Debye-type relaxation processes are resolved in the acoustic spectra, which are assigned to conformational changes between GSH conformers, self-association of GSH, and protonation processes. The standard volume changes for each process were estimated both experimentally and theoretically revealing a close resemblance among them. The higher the effect of the relaxation process in the structure, the greater the induced volume changes. From the temperature dependence of specific acoustic parameters, the thermodynamic characteristics of each process were determined. The experimental FT-IR spectra were compared with the corresponding theoretically predicted vibrational spectra revealing that the GSH dimers and extended conformers dominate the structure of GSH solutions in the high concentration region. The absorption spectra in the ultraviolet region confirmed the gradual aggregation mechanism that takes place in the aqueous GSH solutions. The results of the present study were discussed and analyzed in the framework of the current phenomenological status of the field.

Africa is expected to have a lion’s Share in the world’s population growth by 2050. At the same time, the World Health Organisation (WHO) reported that roughly 3.4 percent (1/25) of African adults live with HIV making the contient the most severely affected by the HIV pandemic. Consequently, this study, the first of its kind, investigates the impact of population growth and HIV incidence on economic growth and economic development in Africa by utilizing the Pooled Mean Group (PMG) estimator on data from 1990 to 2020 across 29 countries. The results show that population growth has a postive long run impact on Gross Domestic Product (GDP) but has a negative long run impact on per capita GDP, albeit the effects are insignificant in the short run. The incidence of HIV has a negative long run impact on both GDP and per capita GDP although its effect is not significant in the short run. The study, therefore, calls for the advancement of family planning practices and the usage of contraceptives to simultaneously control population growth and curb the spread of HIV incidence. The study futher calls for African governments to increase budgetary allocations to the health and education sectors, as these policy perspectives have the potential of increasing the human capital stock and at the same time enhancing the health status of the work force for sustained growth and development.

Major depressive disorder (MDD) is associated with changes in the levels of the cations calcium (Ca) and magnesium (Mg) as well as circulating pro- and anti-inflammatory cytokines. The immune-inflammatory nature of MDD has encouraged researchers to use anti-inflammatory drugs as an adjuvant treatment for MDD. However, the effect of this treatment on cation levels has not been studied. The present study examined a) differences in both cations between drug-naïve MDD patients and controls, and b) the effects of a combination of sertraline and ketoprofen, an anti-inflammatory drug, on Ca and Mg (both total and ionized). In the same patients we also examined the associations between both cations and IL-1β, IL-4, IL-6, IL-18, IFN-γ, TGF-β1, zinc and indoleamine 2,3-dioxygenase (IDO). Clinical improvement was estimated using the Beck Depression Inventory-II (BDI-II) at baseline and after follow up for two months. Serum Ca and Mg (total and ionized) were significantly lower in MDD patients as compared with controls, while treatment significantly increased calcium but decreased magnesium levels. There were significant and inverse correlations between the BDI-II scores from baseline to endpoint and Ca (both total and ionized), but not Mg, levels. The effects of calcium on the BDI-II score remained significant after considering the effects of zinc, IDO and an immune activation z unit weighted composite score based on the sum of all cytokines. There was a significant and inverse association between this immune activation index and calcium levels from baseline to endpoint. In conclusion, reduced levels of both cations play a role in the pathophysiology of major depression. Increased calcium levels are coupled to the clinical efficacy of antidepressants and attenuation of immune activation. The suppressant effect of antidepressants on Mg levels may be a side effect of those drugs. New antidepressant treatments should be developed that increase the levels both Ca and Mg.

Ozonated oil has several benefits for humans, as it contributes to numerous interventions, maintaining the quality of life and the well-being of individuals. Being a natural product, it has few or almost no side effects. Thus, the study aimed to verify the sensitivity and/or resistance of fixed o “Ozonated” and “Non-Ozonated” oils from Mauritia flexuosa (Buriti), Carapa guaianensis (Andiroba) and essential “Ozonated” oils from Menta piperita (Mint), Eugenia caryophyllus (Clove) in different concentrations, against internationally known bacteria from the American Type Culture Collection – ATCC, comparing with the “Non-Ozonated” versions of the respective oils, using the Agar diffusion technique. Thus, it is evident that the ozonation of the fixed oils of Buriti and Andiroba, as well as the essential oils of Mint and Clove, provided significant results, although they were statistically different. The Buriti and Andiroba oil were ineffective in inhibiting microorganisms. On the other hand, the essential oil of Mint and Clove obtained similar activity of inhibition of microorganisms. With regard to Ozonation, the Essential Oil of “Ozonated” Clove provided greater activity than the “Non-Ozonated” one, which inhibited only one tested microorganism, in addition to producing changes in its chemical composition, requiring individualized studies for the ozonation of each essential oil.

Obesity is one of the most prevalent and damaging metabolic conditions and is a risk factor for the development of other disorders that define the metabolic syndrome. Recent studies have identified a significant role of AGE accumulation and RAGE signaling pathways in the underlying mechanisms that cause the chronic inflammatory response present in obesity which, ultimately, leads to adipose tissue dysfunction. Given the current interest and increasing evidence on possible therapeutic opportunities in the AGE-RAGE axis, the purpose of this work is to review the key findings on new small molecules and bioactive compounds that act as AGE or RAGE inhibitors and their effects on metabolic parameters of people with obesity. The search queries were defined according to the following PICO question: “What are the effects of AGE-RAGE antagonism on adipose tissue metabolism and other metabolic parameters of people with obesity? “. Article search was performed in three online databases: PubMed, Scopus, and Web of Science. In the end, 20 studies were selected for this review. Overall, the reviewed molecules showed beneficial effects on body weight, glucose tolerance, insulin resistance, inflammatory profile, and adipose tissue metabolism in mice models with obesity. There are still very few studies on human application of these molecules, but the ones that were reviewed revealed controversial data when compared to animal studies. Therefore, further human clinical trials should be performed to retrieve more conclusive data.

The mechanical properties, structure, and morphology of milled and 3D printed Ti-6Al-4V alloys produced by selective laser melting were investigated in this study. The mechanical properties were investigated by means of nanoindentation, a tensile test, and a three-point bending test. The Atomic Force Microscope (AFM) was used to study the surface topography and roughness of both titanium alloys. The surface structure and phase analysis were studied by a scanning electron microscope (SEM) and through powder X-ray diffraction (XRD). The results from the nanoindentation experiments showed that the 3D-printed sample has higher indentation hardness and modulus than the milled one. The AFM observation of the surface topography of the samples showed that the milled sample has a higher roughness than the 3D-printed one. The tensile test results showed that the 3D printed sample by means of Selective Laser Melting (SLM) technology has about 26% higher tensile strength and smaller elongation than the milled one. The 3-point bending test revealed that the 3D printed Ti-6Al-4V sample has higher flexural strength than the milled one. It was found that the 3D-printed sample has a smaller crystal size than the milled one, which, according to the Hall-Petch relationship, leads to its higher indentation hardness.

The links between rural and urban have often been the subject of study in Portugal. Nevertheless, the asymmetries between rural and urban have not ceased to increase over the last decades, contributing to an imbalance of economic, social, and territorial dimensions between regions. In order to counter this trend, policies to attract the population and tourism have been endorsed but have not been sufficient to promote territorial cohesion. This makes it necessary to rethink the capacity and the potential of rural territories in terms of mobilising their resources and, through them, promoting new and/or renewed relations with urban territories. This article aims to explore and map the links between urban and rural areas by analysing the routes taken by agri-food products, from production to marketing, with the support of a spatial analysis, using Geographic Information Systems (GIS). For that, we analysed a set of specialised and/or gourmet shops in Oorto and Lisbon, and their relations with the territories from which the commercialized agri-food products come. Most of these products originate in the inland rural regions of the country, and there is a clear geographical connection between the shops analysed and specific territories. Thus, it was possible to verify the increase in interest and consumption of agri-food products of rural origin and the spontaneous increase of this type of shop in the cities analysed, as well as identify the target audience of the shops and the spatial influence they have in the respective cities. These shops, in addition to selling agro-food products, are also promoters of rural territories in an urban environment.

The interactions between work and personal life are important for ensuring well-being especially during COVID-19 where the lines between work and home are blurred. Work-life interference/imbalance can result in work-related burnout, which has been shown to have negative effects on faculty members’ physical and psychological health. Although our understanding of burnout has advanced considerably in recent years, little is known about the effects of burnout on nursing faculty turnover intentions and career satisfaction. Thus, this study aimed to test a hypothesized model examining the effects of work-life inference on nursing faculty burnout (emotional exhaustion and cynicism), turnover intentions and ultimately, career satisfaction. A predictive cross-sectional design was used. An online national survey of nursing faculty members was administered throughout Canada in Summer 2021. Nursing faculty who held full-time or part-time positions in Canadian academic settings were invited via email to participate in the study. Data was collected from an anonymous survey housed on Qualtrics. Descriptive statistics and reliability estimates were computed. The hypothesized model was tested using structural equation modeling. Data suggest that work-life interference significantly increase burnout which contribute to both higher turnover intentions and lower career satisfaction. Turnover intentions in turn was negatively associated with career satisfaction. The findings add to the growing body of literature linking burnout to turnover and dissatisfaction, highlighting key antecedents and/or drivers of burnout among nurse academics. These results provide suggestions for suitable areas for the development of interventions and policies within the organizational structure to reduce the risk of burnout during and post-COVID-19 and improve faculty retention.

Human milk (HM) is the gold standard for feeding infants but has been associated with slower growth in preterm infants compared with preterm formula. This systematic review and meta-analysis summarises the post-1990 literature to examine the effect of HM feeding on growth during the neonatal admission of preterm infants with birth weight ≤1500g and/or born ≤28 weeks’ gestation. Medline, PubMed, CINAHL and Scopus were searched, and comparisons grouped as: exclusive human milk (EHM) vs exclusive preterm formula (EPTF), any HM vs EPTF and higher vs lower doses of HM. We selected studies that used fortified HM and compared that with a PTF; studies comparing unfortified HM and term formula were excluded. Experimental and observational studies were pooled separately. The GRADE system was used to evaluate risk of bias and certainty of evidence. Forty-four studies were included with 37 (n =9,963 infants) included in the meta-analyses. In general, due to poor quality studies, evidence of the effect of any HM feeds or higher versus lower doses of HM was inconclusive. There was a possible effect that lower doses of HM compared with higher doses of HM improved weight gain during the hospital admission, and separately, a possible effect of increased head circumference growth in infants fed EPTF vs any HM. The clinical significance of this is unclear. There was insufficient evidence to determine the effects of an exclusive HM diet on any outcomes.

Identifying ambient noise-based (ANb) signatures of streams can help in the estimation of their erosive potential (EP) that promotes reverie landslides and soil losses in the fluvial valleys. This is particularly imperative on flooding or rainy days, leading to stronger erosion-prone conditions (colluvium and boulders) of the valley beds inferred from georadar attribute analysis. Developing such research direction can benefit the local communities, as is the case with the Cerrado region of Brazil, where these phenomena have high destructive potential with social, economic, and climatic implications. For the present study, a seasonal stream in the Federal District of Brazil was investigated by ANb monitoring supported by Ground Penetration Radar (GPR) for site characterization. The ANb monitoring was conducted (at a safe distance) with a seismometer over several durations of dry and rainy conditions. The power spectral density (PSDs) was computed as a function of several variables, including weather conditions (rainfall, wind speed, and pressure), time-frequency spectrograms, and ambient noise displacement root mean square (RMS). This analysis also considered the single station horizontal-to-vertical spectral ratio (HVSR), where rain, wind, pressure, river flow and anthropogenic signatures were evident (at selective frequency ranges). Multi-peaks that emerged on the HVSR curve were further analyzed to identify amplitude and frequency changes, and the three peaks shift on average to a lower position during the rainy period. The GPR amplitude and waveform variation features were attributed to the stratigraphy (i.e., the boundary between valid and invalid regions and coherence value) of the floodplain and regions susceptible to erosion (erosion-prone lithological spots). This approach provides the basis for non-destructive monitoring tools enabling the detection of 'seismic signatures' and weak spots of the fluvial channels for improving environmental management.

Commercial crocodilian farms face significant economic and livestock losses attributed to stress, which may be linked to their adopted husbandry practices. The development of appropriate and modernized husbandry guidelines, particularly those focused on stress mitigation, is impeded by the limited understanding of the crocodilian stress response. Fifteen grower Nile crocodiles were subjected to simulated acute transport stress, with blood samples collected at various intervals post-stress. Plasma levels of corticosterone, dehydroepiandrosterone (DHEA), adrenaline, and noradrenaline were determined using high-performance liquid chromatography. Glucose and lactate were measured using portable meters, and the heterophil-to-lymphocyte ratio (HLR) was determined via differential leucocyte counts. Significant differences were elicited after the stressor, with acute fluctuations observed in the fast-acting catecholamines (adrenaline and noradrenaline) when compared to baseline. Downstream effects of these catecholamines and corticosterone appear to be associated with a persistent increase in plasma glucose and HLR. Lactate also showed acute fluctuations over time but returned to baseline by the final measurement. DHEA, used as a ratio with corticosterone, showed fluctuations over time with an inverted release pattern to the catecholamines. The study highlights the temporal dynamics of physiological markers under acute stress, contributing to understanding crocodilian stress and potentially informing improved farming practices for conservation and sustainable management.

Objectives: This study validated the Japanese version of O’Donovan et al.’s (2020) composite measure of psychological safety scale and examined the associations of psychological safety with mental health and job-related outcomes. Methods: Online surveys were administered twice to Japanese employees with teams of more than three members. Internal consistency and test-retest reliability was tested using Cronbach’s α and intra-class correlation coefficient (ICC). Structural validity was examined using confirmatory factor analysis (CFA) and exploratory factor analysis (EFA). Convergent validity was tested. Multiple linear regression analyses were conducted to examine the relationship between psychological safety and psychological distress, work engagement, job performance, and job satisfaction. Results: Two hundred healthcare workers and 200 non-healthcare workers were analyzed. The Cronbach’s alpha of the total score was 0.92 - 0.96 and ICC was 0.88 - 0.92. CFA demonstrated poor fit, and EFA yielded a two-factor structure, suggesting one factor combined with peers and team. The scale showed good convergent validity. The total score of the scale showed significant associations with all outcomes in adjusted model in all workers. Conclusions: The Japanese version of the measure of the psychological safety scale presented good reliability and validity. Psychological safety is important for employees’ mental health and performance.

Monarch butterflies are a species of conservation priority due to declining overwintering populations in both eastern and western North America. Declines in western overwintering monarchs—more than 99% since monitoring began—are especially acute. However, the degree to which the western monarch is a distinct biological entity is uncertain. In this review, we focus on phenotypic and genetic differentiation between eastern and western monarchs, with the goal of informing researchers and policy-makers who are interested in monarch conservation. Eastern and western monarchs occupy distinct environments and show some evidence for phenotypic differentiation—particularly for migration-associated traits—though population genetic and genomic studies suggest that they are genetically indistinguishable from one another. We suggest future studies that could improve our understanding of differences between eastern and western monarchs. We also discuss the concept of adaptive capacity in eastern and western monarchs as well as non-migratory populations outside of the monarch’s primary North American range.

In this study, sodium alginate (SA) was oxidized with potassium periodate to produce an alginate-based tanning agent. Using OSA as a biodegradable tanning agent and a nano-hydroxyapatite (nano-HAp) low concentration suspension to give flame retardancy to leather, eco-design concepts were applied to establish a chrome-, aldehyde-, and phenol-free tanning process. Micro-DSC, 1H NMR, attenuated total reflection mode Fourier transform infrared spectroscopy (FTIR-ATR), and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS) were used to investigate the complex matrix collagen-OSA-nano-HAp. Micro-differential scanning calorimetry (micro-DSC) was used to assess OSA's ability to interact with collagen and stabilize the collagen-OSA matrix, while 1H unilateral nuclear magnetic resonance (NMR) was used to investigate the aqueous environment and limitations around collagen molecules caused by their association with OSA and nano-HAp. Industrial standard tests were used to assess mechanical properties and fire resistance of the new leather prototype. The findings reported here indicate that both OSA and nano-HAp are suitable alternatives for cleaner tanning technologies and more sustainable leather.

Objectives To determine the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) from animal and plant sources on glucolipid metabolism and lipoprotein subfractions in type 2 diabetic patients with dyslipidemia. Methods Participants were recruited from the diabetes clinic at the Guanlin Hospital, Yixing City in Jiangsu province, China, from March 2017 through June 2017. Ninety participants were randomly assigned to take 3g/day fish oil (FO, containing EPA and DHA), 3g/day perilla oil (PO, containing ALA), or 3g/day blend oil containing fish oil and linseed oil (BO, containing EPA, DHA and ALA) for 3 months. The levels of serum glucose, glycated hemoglobin (HbA1c), C-peptide, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-HDL, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), lipoprotein a (Lp(a)), and free fatty acids were determined at baseline and after the 3 months. In addition, four fatty acids in serum and red blood cells membranes (RBCm) were analyzed using gas chromatography-mass spectrometry. The Lipoprint System was used to determine the lipoprotein subfractions. Results All 90 participants completed the final 3-month follow-up at the end of the study. After three months of intervention, blood glucose and HbA1c levels in the PO group were significantly lower than those at the baseline (p < 0.05). On the other hand, in the BO group, the HbA1c, non-HDL, Apo A1 and Lp(a) levels were significantly lower, while the C-peptide levels were significantly higher after intervention compared to the baseline (p < 0.05). In the FO group, the HbA1c and TG levels were significantly lower after the intervention compared to the baseline (p < 0.05). In addition, at the end of the study, there was significant increase in the levels of DPA and DHA in serum and RBCm of the FO group (p < 0.05), while in the BO group, there was significant increase in the levels of EPA, DPA and DHA in RBCm (p < 0.05). Finally, the FO group had the highest levels of large HDL subfractions compared to the BO and PO groups, but had the lowest levels of small HDL subfractions among the three groups. Conclusion For patients with diabetes, plant-derived ω-3 PUFAs are more effective at controlling blood glucose than animal-derived ω-3 PUFAs. However, animal-derived ω-3 PUFAs play a critical role in controlling blood lipids. Particularly, fish oil can effectively increase the beneficial large HDL subfractions and reduce the nonbeneficial small HDL subfractions. Both the animal- and plant-derived ω - 3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.

Background. This study compares the short- and long-term effectiveness and safety of pramipexole augmentation (PA) and aripiprazole augmentation (AA) for unipolar treatment-resistant depression (TRD). Methods. Patients were recruited in a private out-patients clinic specialized in mood disorders. At intake and at each visit depressive and (hypo)manic symptoms, clinical status, and level of functioning were evaluated with appropriate scales. The trend of outcomes was analyzed using mixed-effect linear regression models. Results. The study includes 81 unipolar TRD patients treated with PA and 51 with AA. After 12 and 24 weeks of treatment with PA, the predicted response (64.1% and 76.2%) and remission rates (49.7% and 72.7%) were significantly higher than the predicted response (32.2% and 38.0%) and remission rates (18.9% and 28.1%) for AA. The improvement in psychosocial functioning was significantly greater and faster in PA than in AA. PA showed significant superiority over AA as a maintenance strategy (time spent ill and psychosocial functioning) up to 12 months. No difference in safety was found at each time point. Conclusions. PA could be an alternative option for short and long-term treatment of unipolar TRD, more effective and similar in safety with AA. These preliminary results need confirmation from randomized clinical trials.

The creation of nano-zero-valent iron (nZVI) by implementing plant extracts is an environmentally friendly process. High antioxidant capacity and phenol content indicated the possibility of oak-nZVI synthesis using oak leaf extract as a stable material with minimal agglomeration. Simultaneously removal of Cd and phosphates and Ni and phosphates was optimized by a statistically designed experiment with a definitive screening design. In terms of significance, 4 input parameters on process productivity were monitored: initial metal concentration (1 - 9 mgL-1), initial ion concentration (1- 9 mgL-1), pH value (2 - 10) and oak-nZVI dosage (2 - 16 ml). Phosphate removal efficiency, in the presence of cadmium, was the most influenced by oak-nZVI dose and cadmium concentration, while pH gave three statistically significant interactions with oak-nZVI dosage, cadmium concentration, and phosphate concentration. Phosphate removal efficiency, in the presence of Ni, is the most influenced by nickel concentration, phosphate concentration, pH, two-factor interaction between nZVI dose and Ni concentration, and quadratic phosphate interaction. The process optimization yielded the highest simultaneous removal efficiency of 98.99% and 87.30% for cadmium and phosphate ions, respectively. Also, the highest simultaneous removal efficiency of nickel and phosphates ion was 93.44% for 96.75%, respectively. The optimization process fits into the confidence intervals, confirming the assumption that the adopted regression model describes the process well. This work demonstrated an enormous potential and prosperous application for the Cd(II), Ni(II), and phosphate removal from water matrices.

Kummerowia striata is a traditional medicine used for the therapy of inflammation-related diseases. Herein, we investigated the anti-melanogenic and antioxidant activities of an ethanolic extract of K. striata (EKS) using a number of in vitro and cell culture model systems. The anti-melanogenic effect was assessed in B16F10 melanoma cells based on melanin synthesis and in vitro tyrosinase inhibitory activity and the anti-oxidant activity assays were performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS); EKS exhibited strong anti-oxidant activities in both the assays. The expression of tyrosinase, tyrosinase-related protein 1, tyrosinase-related protein 2, and microphthalmia-associated transcription factor was decreased in a dose-dependent manner at mRNA and protein levels upon treatment with EKS. Notably, EKS did not affect the cell viability at all the EKS concentrations used in this study, indicating that EKS-mediated inhibition of melanin synthesis is not accompanied with cytotoxicity. Collectively, our findings demonstrate, for the first time, that EKS possesses anti-melanogenic and anti-oxidant activities, and suggest that further evaluation and development of EKS as a functional supplement or cosmetic might be useful for skin whitening and for reduction wrinkles.

Spodoptera frugiperda is a significant economic pest of maize in Uganda. Many Ugandan maize farmers employ synthetic insecticides as their main form of control despite the negative impacts of these chemicals. The study aimed to determine the effect of synthetic, semi-synthetic and bio-pesticides on maize leaf damage, and abundance of S, frugiperda and its parasitoids in Wakiso and Lira districts. The experiments were laid out in an RCBD with six treatments in 2020 and nine treatments in 2021, replicated four times. The treatments with the biggest decrease in leaf damage and infestation were Amdocs and Roket®, followed by Nimbecidine. The biopesticides were not always more effective than the untreated control, though; their efficacy was often lower than that of synthetics, semi-synthetics, and botanical. We recovered one egg parasitoid, Telenomus remus, and seven egg and egg-larval parasitoids (Coccygidium luteum, Coccygidium sp., Cotesia icipe, Chelonus sp., Micranisa sp., Charops cf. diversipes, and Tachinidae sp. Among these, C. cf diversipes, Chelonus sp., C. luteum, C. icipe and Tachinidae were the most abundant. Parasitism was low, averaging 10% for eggs and 5.3% for larvae. Synthetic, the semi-synthetic and Nimbecidine often increased higher yield when compared with the untreated control. There were genrally low population of parasitoids, althoguh there were some indications of reduced population of parasitoids in plots treated with Amdocs and Roket®, while percent parasitism was not affected. In some instances, higher yields were even realized in untreated control. While considering the tactics to integrate, assessing the practices more compatible with biological practices will be necessary.

Background: The SARS-CoV-2 virus is a new highly pathogen virus that can suppress cell immune response (Poly ADPR process, and interferon releasing in infected cell) by viral macrodomain and create fatal pneumonia. Cytokine storm phenomenon which can create consequence of SARS COV-2 by increase of the performance of human TRPM2, is a dangerous condition for human and its body organ such as kidney, heart, and liver. it seems like prevention of beginning of these events is necessary. Material and methods: in this study drug and drug like database was used for inhibition of the viral macrodomain and human TRPM2 that can initiate of the viral cell cycle infection and human cytokine storm respectively. Ligand base drug designed, pharmacophore modeling, docking and molecular dynamic simulation was performed Results: among up to billion compounds, 20 compounds were screened by infinisee program. Then 7 compounds were selected by pharmacophore modeling. between 7 compounds, 5 compound was removed because of high similarity to ADPR and possibility of toxic effect for human RNA and DNA polymerase. One compound was losartan and selected for docking and molecular dynamic simulation. Conclusion: losartan earned a proper dock score and binding affinity to create the complexes with TRPM2 and macrodomain. Molecular dynamic simulation has shown losartan had an adequate binding free energy for human trpm2 and viral macrodomain. The inhibitory effect of losartan on these protein has shown and it could interfere in several points (PARP, PARG- macrodomain and TRPM2) and decreases oxidative stress, apoptosis, cytokine storm in COVID-19.