The microalgae Phaeodactylum tricornutum (PT) is distinguished by its rich nutrient profile, characterized by well-documented neuroprotective activities, including fucoxanthin (FX), a major carotenoid, and polyunsaturated omega-3 fatty acids (n-3 PUFA). The current study aims to evaluate the protective effects of a standardized extract of PT (Mi136) containing 2% FX on cognitive function, oxidative stress, and inflammation parameters in a mouse model of accelerated aging. Seventy-two (72) male mice were randomly assigned to the blank control group (BC), negative control group (NC), and four similar microalgae extract of PT groups (branded as BrainPhytTM) with different human equivalent doses. From day 01 to day 51, mice in the BC group were injected with a 0.9% normal saline solution, while mice in all other groups were subcutaneously injected with D-galactose (D-Gal) at a dose of 150 mg/kg once per day, five days per week. Results indicated that, for the three higher microalgae extract of PT dose groups, spatial cognitive function, swim latency, and step-through latency impairments induced by chronic D-Gal intoxication were significantly and fully inhibited, with mean values similar to those in the BC group during each day of testing. Similar benefits were observed in biochemical analysis, specifically regarding brain and plasma levels of lipid peroxidation, TNF-α, and IL-6 markers. These data underscore the positive effects of a standardized extract of PT containing 2% FX on cognitive function parameters such as spatial working memory, long-term memory, and short-term memory through the regulation of oxidative stress and inflammation pathways.

Small-scale fisheries are significant sources of nutrition and livelihood globally. However, increasing anthropogenic activities in coastal areas of developing countries have threatened the sustainability of artisanal fisheries and species. Fisheries of Sardinella maderensis (Lowe, 1838), to which Nigeria contributes 9% of the global stock and is a significant livelihood source in the coastal communities of Ibeju-Lekki, Lagos, face sustainability threats. This research investigated the effects of anthropogenic activities on S. maderensis fishery in the coastal areas of Ibeju-Lekki, Lagos, Nigeria. The study adopted a mixed-method approach involving qualitative and quantitative research methods. These include species identification, water quality analysis, land use change analysis, field surveys, focus group discussions and interviews. Results show genetic analysis of the fish samples from six stations revealed that the species had a mean of 98% similarity to Sardinella maderensis in NCBI. Multiple linear regression indicates that anthropogenic variables explained approximately 4.62% of the variance in the fish catch (p < .001, R2 = .05). Water samples showed heavy metal levels were above international limits, high total petroleum hydrocarbon (TPH) pollution in all stations (27.56 mg/L- 3985.40 mg/L). Physiochemical analysis of water samples indicated TDS higher than acceptable limits (Mean = 24971.1 mg/L) and inadequate chlorophyll-a level (Mean = 0.01 µg/L). Hence, urgent strategies are required to mitigate anthropogenic threats through inclusive coastal management policies supporting resilient artisanal fisheries and marine spatial planning.

Phelipanche ramosa is a root parasitic plant fully dependent on host plants for nutrition and development. Once germinated, the parasitic seedling develops inside of the infected roots a specific organ, the haustorium, thanks to notably cell wall degrading enzymes of haustorial intrusive cells and induced modifications in host’s cell walls. The model plant Arabidopsis thaliana is susceptible to P. ramosa, thus mutants in cell wall metabolism, notably in pectin remodeling like Atpme3-1, are of interest in studying the involvement of cell wall degrading host’s enzymes in establishment of the plant-plant interaction. Host-parasite co-cultures in mini-rhizotrons systems revealed that parasite attachments are twice more numerous and tubercle growth is quicker on Atpme3-1 roots than on WT roots. When compared to the WT, increase in susceptibility in the mutant is associated to reduction in PME activity in roots and to lowering in the degree of pectin methylation at the host-parasite interface, as detected immunohistochemically in infected roots. In addition, both WT and Atpme3-1 responded to infestation by modulations in expression of PAE and PME encoding genes and in global related enzymes activities in roots, before and after parasite attachment. However, modulations differ in WT and Atpme3-1 and this may contribute to different pectin remodeling in roots and contrasted susceptibility to P. ramosa. By this integrative study, we could define a model of the cell wall response to this particular biotic stress and indicate for the first time the role of PME3 in this parasitic plant-plant interaction.

High-power output and high conversion efficiency are crucial in the study of microfluidic microbial fuel cells (MFCs). In our previous work, we attempted various methods to increase the power density of the MFCs, but nutrient consumption was limited to the bottom (electrode) layer of the microfluidic channel due to the diffusion limitations. In this work, long-term experiments were conducted on a new 4-electrode microfluidic MFC design, which grew Geobacter sulfurreducens biofilms on upward- and downward-facing electrodes in the microchannel. It was discovered that inoculation and growth of the electroactive biofilm did not proceed as fast as the downward facing anode, which we hypothesize is due to gravity effects that negatively impacted bacterial settling on that surface. Rotating the device during the growth phase resulted in uniform and strong outputs from both sides, yielding individual power densities of 4.03 and 4.13 W m-2, which was increased to nearly double when the top- and bottom-side electrodes were operated in parallel as a single 4-electrode MFC. Similarly, acetate consumption could be doubled with the 4-electrodes operated in parallel.

Phosphite (Phi) has gained attention in agriculture due to its biostimulant effect on crops. This molecule has been found to benefit plant performance by providing protection against pathogens, improving yield and fruit quality, and improving nutrient and water use efficiency. It is still unclear how Phi enhances plant growth and protects against multiple stresses. It has been hypothesized that Phi acts by directly affecting the pathogens and interacting with the plant cellular components and molecular machinery to elicit defense responses. This study delves into elucidating the mechanisms underlying Phi’s beneficial effects on plants, revealing a complex interplay with fundamental signaling pathways. A RNA-seq study of Arabidopsis seedlings under optimal and limiting phosphate conditions helped us unveil Phi’s role in promoting plant growth by activating the expression of genes involved in the biosynthesis and signaling pathways associated with abscisic acid (ABA), salicylic acid (SA), and jasmonic acid (JA). Expression of ABA-related genes, known for their involvement in stress response and development regulation, is triggered by Phi treatment, contributing to enhanced resilience and growth. Simultaneously, the activation of the SA pathway, associated with defense responses, suggests Phi’s potential in bolstering plant immunity. Moreover, Phi influences JA biosynthesis and signaling, which are crucial for defense against herbivores and pathogens, thereby strengthening plants’ defenses. Our findings reveal a multifaceted mechanism through which Phi benefits Arabidopsis development. Understanding its intricate interplay with key signaling pathways opens avenues for leveraging Phi as a strategic tool to enhance plant resilience, immunity, and growth in agricultural and ecological contexts.

Solventogenic Clostridium species are important for establishing sustainable industrial bioproduction of fuels and important chemicals. The inherent versatility of these species in substrate utilization and the range of solvents produced during acetone butanol-ethanol (ABE) fermentation make solventogenic Clostridium an attractive choice for biotechnological applications such as production of fuels and chemicals. The functional qualities of these microbes have thus been identified to be due to complex regulatory networks that play essential roles in modulating the metabolism of this group of bacteria. Genomes of solventogenic Clostridium species have relatively greater prevalence of genes that are intricately controlled by various regulatory molecules than most other species. Consequently, the use of genetic or metabolic engineering strategies that do not consider the underlying regulatory mechanisms will not be effective. Several regulatory factors involved in substrate uptake/utilization, sporulation, solvent production, and stress responses (Carbon Catabolite Protein A, Spo0A, AbrB, Rex, CsrA) have been identified and characterized. In this review, the focus is on newly identified regulatory factors in solventogenic Clostridium species, the interaction of these factors with previously identified molecules, and potential implications on substrate utilization, solvent production, and resistance/tolerance to lignocellulose-derived microbial inhibitory compounds.

Cinnamomum tamala leaf (CTL), also known as tejpat and Indian bay leaf, is used all over the world for seasoning, flavouring, and medicinal purposes. Numerous researchers are interested in exploring the nutritional and medicinal benefits of CTL due to their potential as nutraceuticals. These characteristics could be explained by the presence of several essential bioactive substances and lipid derivatives. There are no reports available on this species about its metabolites profile. In this work, rapid screen and identify chemical compounds in supercritical (SC)-CO2 extracts of CTL by use of UPLC-Q-TOF-MSE with multivariate statistical analysis approach was established in both negative and positive mode. As a results, a total of 166 compounds, including 66 monocarboxylic fatty acids, 52 dicarboxylic fatty acids, 27 fatty acid amides, and 21 others were tentatively identified based on accurate mass, and the mass spectrometric fragmentation pattern, out of which 142 compounds are common and found in all five CTL extracts. They displayed robust [M+H]+ and/or [M-H]- ions in both low- and high-energy collision-induced dissociations (CIDs). Based on chemical profiling and chemometric analysis, CTL4 (300bar/55°C) extract was found significantly more potent in other CTL’s extracts. A new mono- and di-carboxylic fatty acids, fatty acid amides and other essential bioactive compounds were separated within 20 min runtime and identified in CTL for the first time. The combination of UPLC-Q-TOF-MSE and chemometric analysis is a powerful method to rapidly screen the metabolites profile for the quality control of C. tamala leaf.

Helicobacter Pylori (H. Pylori) is a common pathogen with high prevalence of infection in human populations. Diagnosis of H. Pylori infection is critical for its treatment, eradication, and prognosis. Biosensors have been demonstrated to be powerful for rapid onsite detection of pathogens, particularly for point-of-care test (POCT) scenarios. In this work, we propose a novel optical biosensor, based on nanomaterial porous silicon (PSi) and photonic surface state Tamm Plasmon Polariton (TPP), for detection of cytotoxin-associated antigen A (CagA) antigen of H. Pylori bacterium. We fabricated the PSi TPP biosensor, analysed its optical characteristics and demonstrated through experiments towards sensing of CagA antigen, that TPP biosensor has sensitivity of 100 pm/(ng/ml), limit of detection of 0.01 ng/ml, and specificity in terms of positive-to-negative ratio of more than six. From these performance factors, it can be concluded that TPP biosensor can serve as an effective tool for diagnosis of H. Pylori infection, either in analytical labs or in POCT applications.

To date, various chimeric lysins have been developed as efficacious antibiotics against multidrug-resistant bacteria, but direct comparisons of their antibacterial activities have been difficult due to the preparation of multiple recombinant chimeric lysins. Previously, we reported an E. coli cell-free expression method to screen better chimeric lysins against Staphylococcus aureus, but we still needed to increase the amounts of expressed proteins enough to be able to detect them non-isotopically for quantity comparisons. In this study, we improved the previous cell-free expression system by adding a previously reported artificial T7 terminator and reversing the different nucleotides between the T7 promoter and start codon to those of the T7 phage. The new method increased the expressed amount of chimeric lysins enough for us to detect them using Western blotting. Therefore, the qualitative comparison of activity between different chimeric lysins has become possible via the adjustment of the amount variables between samples without protein purification. We applied it to select more active chimeric lysins derived from our previously reported chimeric lysin (ALS2). Finally, we compared the antibacterial activities of our selected chimeric lysins with reported chimeric lysins (ClyC and ClyO) and lysostaphin, and determined the rank orders of antibacterial activities on different S. aureus strains in our experimental conditions.

Information geometry (IG) is a fascinating combination of differential geometry and statistics where a Riemannian manifold's structure is applied to a statistical model. It may find numerous fascinating uses in the domains of theoretical neurology, machine learning, complexity, and (quantum) information theory, among others. (IG) aims to provide a differential-geometric perspective on statistical geodesic models' structure. In this case, IG, KD, and J-divergence (JD) are used to define the manifold of the Generalised Brownian Motion (GBM). Consequently, the geodesic equations (GEs) are devised, and GB information matrix exponential (IME) is presented. Moreover, for first time ever, the necessary and sufficient mathematical requirement that characterizes the developability of Generalized Brownian Motion(GBM) manifold is devised. Also, a novel sufficient and necessary conditions which characterizes the regions where the surface describing GBM is minimal is determined. Also, it is shown that GBM has a non-zero 0-Gaussian and Ricci curvatures. Consequently, this advances the establishment of a unified GBM- Relativistic Info-Geometric based analysis.

Recently, Shehata et al. [37] introduced the r+1Rs(B;C; z) matrix function and established some properties. The aim of this study established to devote and derive certain basic properties including analytic properties, recurrence matrix relations, dierential properties, new integral representations, k- Beta transform, Laplace transform, fractional k-Fourier transform, fractional integral properties, the k-Riemann{Liouville and k-Weyl fractional integral and derivative operators an extended version of r+1Rs;k matrix function. We establish its relationships with other well known special matrix functions which have some particular cases in the context of three parametric Mittag-Leer matrix function, k- Konhauser and k-Laguerre matrix polynomials. Finally, some special cases of the established formulas are also discussed.

Background: Smad4, a critical tumor suppressor gene, plays a significant role in pancreatic biology and tumorigenesis. Genetic background and sex are known to influence phenotypic outcomes, but their impact on pancreatic weight in Smad4-deficient mice remains unclear. This study investigates the impact of Smad4 deficiency on pancreatic weight in F1 mice from diverse Collaborative Cross (CC) lines, focusing on the influence of genetic background and sex. Methods: F1 mice were generated by crossbreeding female CC mice with C57BL/6J-Smad4tm1Mak males. Genotyping confirmed the presence of Smad4 knockout alleles. Mice were housed under standard conditions, euthanized at 80 weeks, and their pancreatic weights were measured, adjusted for body weight, and analyzed for effects of Smad4 deficiency, sex, and genetic background. Results: The overall population of F1 mice showed a slight but non-significant increase in adjusted pancreatic weights in heterozygous knockout mice compared to wild-type mice. Sex-specific analysis revealed no significant difference in males but a significant increase in adjusted pancreatic weights in heterozygous knockout females. Genetic background analysis showed that lines CC018 and CC025 substantially increased adjusted pancreatic weights in heterozygous knockout mice. In contrast, other lines showed no significant difference or varied non-significant changes. The interplay between genetic background and sex further influenced these outcomes. Conclusion: Smad4 deficiency affects pancreatic weight in a manner significantly modulated by genetic background and sex. This study highlights the necessity of considering these factors in genetic research and therapeutic development, demonstrating the value of the Collaborative cross-mouse population in dissecting complex genetic interactions.

The jalapeño pepper is a vegetable of great economic importance worldwide. However, low germination efficiency, weak seedlings, and a high mortality rate during transplant compromise the viability and sustainability of the crop. An innovative solution is the nanopriming tech-nique, an emerging and novel technology, which involves the imbibition of seeds for a specific period using mineral nanoparticles. The addition of micronutrients such as Zinc and Molyb-denum has been used in seed germination and early seedling development due to their crucial roles. The aim of this study was to evaluate the effectiveness of using Zinc-Molybdenum nano-priming in Jalapeño Pepper on germination and early growth. The results showed that applying nanopriming 124-10 mg L−1 of Zinc-Molybdenum promotes effectiveness on the imbibition and germination of jalapeño pepper seeds, resulting in heavier seeds with better initial absorption. This method not only improves germination rates and seedling vigor but also points towards more sustainable and efficient agriculture. Building on these findings, the Zinc-Molybdenum nanopriming method could potentially transform jalapeño pepper cultivation by enhancing seed quality and resilience. This could lead to more robust crop yields and reduce the need for chemical inputs such as fertilizers and pesticides, thus lowering production costs and environ-mental impact.

In the paper, we prove a joint limit theorem in terms of weak convergence of probability measures on $\mathbb{C}^2$ defined by means of the Epstein ζ(s;Q) and Hurwitz ζ(s,α) zeta-functions. The limit measure in the theorem is explicitly given. For this, some restrictions on the matrix Q and parameter α are required. The theorem obtained extends and generalizes Bohr-Jessen’s results characterising asymptotic behaviour of the Riemann zeta-function.

Predators are dependent on the capture of prey to meet their energetic and nutritive requirements, imposing a regime of predation risk. Consequently, prey experience both consumptive and non-consumptive effects. Non-consumptive effects may manifest through altered growth and ontogenetic trajectories of prey species, a dynamic modulated by olfactory or other sensory cues from predators. Bactrocera dorsalis Hendel represents a great invasive threat to global horticulture. While earlier research has primarily centered on the consumptive interactions between B. dorsalis and its natural enemies, the potential consequences of non-consumptive interactions on the development of B. dorsalis have been overlooked. In this study, we investigated the impact of predation risk effects, induced by both visual exposure to the predatory mantis Hierodula patellifera Serville and its associated odor, on the life history traits of B. dorsalis. Female B. dorsalis demonstrated reduced development time in the presence of isolated H. patellifera or H. patellifera odor, yet evidenced significantly increased fecundity. Conversely, males displayed no significant change in development time. Additionally, neither female nor male body weight at death was significantly influenced by predation risk from isolated predators or predator odor. These results indicated adaptive developmental strategies of B. dorsalis when faced with risks from predators and highlight the important role of predator odor, which has the potential to lay the groundwork for improving biological control efforts and innovative approaches within pest control.

Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigates B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq Tannic acid / 100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq Chlorogenic acid / 100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC–HRMS/MS) and HPLC and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods; our results could explain the protective effects of Berberidis cortex EC50FRAP = 0.1398 mg/mL, IC50ABTS = 0.0442 mg/mL, IC50DPPH = 0.2610 mg/mL compared to ascorbic acid (IC50 = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and Berberine - Berberine sulfate hydrate (BS) - investigated on Daphnia sp reported significant BS toxicity after 24 h; BVE revealed considerable toxicity after 48 hours and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated on different tumor cell lines after 24 and 48 hours of treatments. The MTS assay evidenced a dose- and time-dependent antiproliferative activity, higher on BS than BVE. The strongest diminution of tumor cell viability was recorded on breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC50 < 100 µg/mL). However, no cytotoxicity was reported on normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE's concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines.

There are laws and rights aimed at people with disabilities, especially those with Mild Intellectual Disability (LDD), who actively participate in society but face barriers in learning and participating in various activities. In Colombia, where 1.3 million people with disabilities are registered, 16.8% correspond to the category of DIL, some of whom are part of the economically active population. Despite this, significant employment gaps persist.In order to address this gap, this research focuses on the analysis of the specific problems related to the labor inclusion of people with IDL in logistics environments, particularly in cold rooms. The aim is to prevent occupational hazards through the application of Industry 4.0 technologies.Through the collaboration of the Analytics and Design Research Seedbed, with entrepreneurs and experts in the field, significant challenges in labor inclusion in low-temperature environments were identified. The agile Scrum methodology was used to develop a prototype of an application that addresses these issues. This prototype meets the functional and non-functional requirements necessary to ensure the protection and prevention of risks for workers with DIL who perform functions in refrigerated rooms.This prototype manages to provide an inclusive alternative for people with disability Intellectual Light, challenging business cultural paradigms, by integrating mobile devices with Industry 4.0 technologies, encouraging greater interaction between machines and human beings, thus prioritizing the health and safety of employees in their daily activities.

Transitions from seed to seedling represent a critical developmental step in the life cycle of higher plants, dramatically affecting plant ontogenesis and stress tolerance. The release from dormancy to acquiring the germination ability is defined by a balance of phytohormones, with a substantial contribution of abscisic acid (ABA), which inhibits germination. We studied the embryonic axes of Pisum sativum L. before and after radicle protrusion. Our previous work compared RNA sequencing-based transcriptomics in the embryonic axes isolated before and after radicle protrusion. The current study aims to analyze ABA-dependent gene regulation during the transition of embryonic axes from germination to post-germination stage. First, we determined the levels of abscisates (ABA, phaseic acid, dihydrophaseic acid, and neo-phaseic acid) using the ultra-high-performance liquid chromatography-tandem mass spectrometry. Second, we made a detailed annotation of ABA-associated genes using RNA sequencing-based transcriptome profiling. Finally, we analyzed the DNA methylation pattern in the promoters of the PsABI3, PsABI4, and PsABI5 genes. We showed that changes in the abscisate profile are characterized by the accumulation of ABA catabolites, and the ABA-related gene profile is accompanied by the upregulation of genes controlling the seedling development and the downregulation of genes controlling the water deprivation. The expression of ABI3, ABI4 and ABI5, which encode the crucial transcription factors during late maturation, was downregulated by more than 20-fold, and their promoters exhibited a high level of methylation already at the late germination stage. Thus, although ABA remains important, other regulators seems to be involved in the transition from seed to seedling.

In the face of climate change, bringing more useful alleles and genes from wild relatives of wheat is crucial to develop climate-resilience varieties. We used two populations of backcrossed recombinant inbred lines (BIL1 and BIL2), developed using two intra-specifically diverse Aegilops tauschii accessions from lineage 1 and lineage 2, respectively, and backcrossing to common wheat cultivar ‘Norin 61’. The study aimed to identify quantitative trait loci (QTL) associated with heat stress (HS) tolerance. The two BILs were evaluated under heat stress environments in Sudan for phenology, plant height (PH), grain yield (GY), biomass (BIO), harvest index (HI), and thousand kernel weight (TKW). Grain yield was significantly correlated with BIO and TKW under HS; therefore, stress tolerance index (STI) was calculated for these traits as well as for GY. A total of 16 heat tolerant lines were identified based on GY and STI-GY. The QTL analysis performed using inclusive composite interval mapping identified a total of 40 QTLs in BIL1 and 153 QTLs in BIL2 across all environments. We detected 39 QTLs associated with GY-STI, BIO-STI, and TKW-STI in both populations (14 in BIL1 and 25 in BIL2). The QTL associated with STI were detected on chromosomes 1A, 3A, 5A, 2B, 4B, and all the D-subgenomes. We found that QTL detected only under HS for GY on chromosome 5A, TKW on 3B and 5B, PH on 3B and 4B, and grain filling duration on 2B. The higher number of QTLs identified in BIL2 for heat stress tolerance suggests the importance of assessing the effects of intraspecific variation of Ae. tauschii in wheat breeding as it could modulate the heat stress responses/adaptation. Our study provides useful genetic resources for uncovering heat-tolerant QTLs for wheat improvement for heat stress environments.

Limited research has been conducted on the metabolites present in the essential oils (EOs) of Phlomoides rotata (Benth. ex Hook. f.) Mathiesen (PR, syn. Lamiophlomis rotata (Benth.) Kudô), and their potential pharmacological activities, such as antioxidant properties, are often overlooked. We conducted a metabolomics-based screening to identify the characteristic metabolites (CMs) in the EOs extracted from PR. Meanwhile, we evaluated their in vitro antioxidant activities (AOAs). The EOs obtained through hydro-distillation are characterized by a light yellow color and a fresh, elegant fragrance. Cryoprecipitation was used to separate the crystals (Crs) from the EOs, resulting in the crystal-free EOs (CFs). A total of 121 components are identified and quantified in the EOs, Crs, and CFs. Among them, 84 were reported for the first time from such EOs. The major compounds include long-chain fatty acids (LCFAs) and their esters, such as palmitic acid (PA), myristic acid (MA), linoleic acid (LA), oleic acid (OA), stearic acid, and methyl palmitate (MP). Furthermore, 11 kinds of apocarotenoids (also called norisoprenoids) were first systematically investigated. Among them, eight C13-norisoprenoids, with trans-β-damascenone (DN) being particularly notable for its flavor, were identified. A sum of 11 CMs are screened , including PA, MA, LA, OA, MP, hexahydrofarnesyl acetone, phytol (PT), DN, stearic acid, linalool, and hexanal. These CMs are biosynthesized through FAs and 2-C-Methyl-D-erythritol 4-phosphate/1-Deoxy-D-xylulose 5-phosphate pathways. The in vitro AOAs of EOs, Crs, CFs, and seven selected CMs (PA, MA, LA, OA, MP, PT, and DN) were evaluated. Generally, PA and MA exhibited pro-oxidant activities (POAs) or weak AOAs. LA and OA demonstrated POAs or weak AOAs at lower concentrations, but at higher concentrations, they displayed medium to strong AOAs. Importantly, the CFs typically exhibited stronger AOAs compared to the corresponding EOs and Crs, potentially due to variations in their PA content. Overall, this study provides valuable insights into the potential utilization of EOs from PR.

Abstract: Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the devel-opment of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granu-lomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.

The prevalence of multidrug-resistant Gram-negative infections, particularly carbapenem-resistant strains, has become a significant global health concern. Ceftazidime-avibactam (CZA) has emerged as a promising treatment option. However, data on its efficacy and safety in children are scarce, necessitating further investigation. We conducted a retrospective study at a tertiary hospital in Spain from February 2019 to January 2022. Pediatric patients (<16 years) treated with CZA for confirmed or suspected multidrug-resistant Gram-negative infections were included. Clinical and microbiological characteristics, treatment approaches, and outcomes were examined. Eighteen children received CZA treatment. All had complex chronic conditions, with the most frequent underlying main diseases being liver transplantation (n=8) and biliary atresia (n=4). The predominant type of infection for which they received CZA was intra-abdominal infections caused or suspected to be caused by OXA-48-producing Klebsiella pneumoniae. CZA was generally well tolerated. Within the first month of starting CZA therapy, 2 patients died, with one case directly linked to the infection’s fatal outcome. Some patients needed repeated courses of therapy due to recurrent infections, yet no resistance development was noted. In summary, the use of CZA showed effectiveness and safety, while the lack of resistance development highlights CZA’s potential as a primary treatment option against OXA-48-producing infections.

The study assessed the trapping efficacy of locally-modified 1) Gravid Aedes Trap(GAT) lined with insecticide-treated net (ITN) as a killing agent, 2) Autocidal Gravid Ovitrap(AGO) with sticky board in the semi-field system (SFS) and field setting. Fully-balanced Latin square experiments were conducted to compare GAT lined with ITN vs AGO, both with either yeast or grass infusion. Biogents-Sentinel (BGS) with BG-Lure and no CO2 was used as standard trap for Aedes mosquitoes. In the SFS, GAT outperformed AGO in collecting both nulliparous (65% vs 49%,OR=2.22,[95%CI:1.89-2.60],p

Blocking the interaction of the SARS-CoV-2 spike protein with the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim in this study was to explore the efficacy of TCM treatments for SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. The antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis was found to be effective against SARS-CoV-2 infection through affecting the interaction of viral spike protein with the hACE2 protein. The active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside, respectively, found in S. baicalensis, exhibited strong inhibitory activities, targeting the viral spike protein or hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors of the interaction of the Omicron spike protein and hACE2 receptor from S. baicalensis. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed.

A reduction of melatonin function contributes to the acceleration of Alzheimer's disease (AD), and understanding molecular processes of melatonin-related signaling is critical for intervention of AD progression. Recently, we synthesized and tested a series of melatonin derivates with donepezil fragments in silico and in vitro. In this study, one of the most potent compounds, 3c, was studied in an in vivo rat model of pinealectomy (pin) and subsequent icvAβ1-42 infusion. Melatonin was used as a referent drug. The treatment with melatonin and 3c (10 mg/kg, i.p. for 14 days) exerted a beneficial effect on memory decline and concomitant rise of Aβ1-42 and pTAU in the hippocampus in the pin + icvAβ1-42 rats. Melatonin supplementation facilitated the non-amyloidogenic signaling via a non-receptor (histone deacetylase sirtuin 1, SIRT1) and receptor-related signaling (MT/ERK/CREB). The hybrid 3c derivate up-regulated the MT1A and MT2B receptors, pERK and pCREB. Our findings strongly support the hypothesis that melatonin-related derivates may become a promising drug candidate in AD therapy.

To delve into the structure-function relationship of transmembrane proteins (TMPs), robust protocols are needed to produce them in a pure, stable, and functional state. Among all hosts that express heterologous TMPs, E. coli has the lowest cost and fastest turnover. However, many of the expressed in E. coli TMPs are misfolded. Several strategies have been developed to either direct the foreign TMPs to E. coli’s membrane or retain them in a cytosolic soluble form to overcome this deficiency. Here, we summarize protein engineering methods to produce chimera constructs of the desired TMPs fused to either signal peptide or precursor maltose binding protein (pMBP) to direct the entire construct to the periplasm, therefore depositing the fused TMP in the plasma membrane. We further describe strategies to produce TMPs in soluble form by utilizing N-terminally fused MBP without signal peptide. Depending on its N- or C-terminus location, a fusion to apolipoprotein A-I can either direct the TMP to the membrane or shield the hydrophobic regions of the TMP, maintaining the soluble form. Strategies to produce G-protein coupled receptors, TMPs of Mycobacterium tuberculosis, HIV-1 Vpu, and other TMPs are discussed. This knowledge could increase the scope of TMPs’ expression in E. coli.

The spatial and temporal variability in dietary preferences of juvenile three-spined stickleback Gasterosteus aculeatus, was studied across typical coastal habitats of Keret Archipelago, Kandalaksha Bay, the White Sea. Sampling of fish using beach seine was implemented in late July-early August and in late August, and zooplankton samples were collected to make a quantitative evaluation of abundance of potential prey items. Similarity Percentage (SIMPER) analysis implemented over the data obtained from stomach content analysis revealed five planktonic taxa mostly contributing to the diet of juvenile sticklebacks, of which copepod Temora longicornis was the most important prey item at marine sites, while Acartia longiremis prevailed in diet of fishes in marine lagoon. Calculation of selectivity index demonstrated that some taxa (e.g., A. longiremis) were always avoided by juvenile fishes, others (e.g. Microsetella norvegica) were firstly avoided and then selected in late August. Calculation of selectivity index was implemented per sample and per individual fish indicated that taxa like T. longicornis and were selected during the whole period of study, fishes demonstrated pronounced individual variation in prey selectivity. In general, data on selectivity indicated that despite juvenile sticklebacks feed on mostly available prey items, they can demonstrate taxonomic and size-specific prey selectivity.

Kininogens are multidomain glycoproteins found in the blood of most vertebrates. They are important in the blood coagulation cascade pathways - in intrinsic pathway activation leading to thrombin generation partially independently from tissue factor dependent extrinsic pathway, connecting blood coagulation with the kallikrein-kinin system. Nothing is known about the shape on atomic level therefore the endeavor to obtain the good-quality spatial structure of kininogens is important for a better understanding of their role in disease and treatment. Application of cryo-EM is important for solving the spatial structure of kininogens, drawing new frontiers in understanding the function and opening new pathways for drug development.

For gravitational wave (GW) detected neutron star mergers, one of the leading candidates for electromagnetic (EM) counterparts is the afterglow from an ultra-relativistic jet. Where this afterglow is observed, it will likely be viewed off-axis, such as the afterglow following GW170817/GRB 170817A. The temporal behaviour of an off-axis observed GRB afterglow can be used to reveal the lateral jet structure, and statistical model fits can put constraints on the various model free-parameters. Amongst these parameters is the inclination of the system to the line of sight. Along with the GW detection, the afterglow modelling provides the best constraint on the inclination to the line-of-sight and can improve the estimates of cosmological parameters e.g. the Hubble constant, from GW-EM events. However, modelling of the afterglow depends on the assumed jet structure and, often overlooked, the effects of lateral spreading. Here we show how the inclusion of lateral spreading in the afterglow models can affect the estimated inclination of GW-EM events.

Negative corona discharges occur widely in high voltage transmission lines and charged aircraft, which can cause strong electromagnetic interference. Negative corona discharge is typically performed simultaneously at multiple discharge points. In this study, the current and its EM radiation characteristics of single-needle and multi-needle negative corona discharge in different conditions were tested. The current and electromagnetic radiation characteristics of the two discharge structures were compared. The dipole radiation model was established to analyze the EM radiation characteristics of the negative corona discharge.The results show that, It is only when the voltage reaches a certain threshold that the current and electromagnetic radiation fields of the multi-needle discharge structure will be superimposed and their amplitudes will increase significantly. The frequency of electromagnetic radiation signal does not change with the number of needles, cathode geometry and applied voltage, but only depends on ambient pressure. It provides a basis for detecting corona discharge sources under different conditions.

Abstract Octreotide is the first synthetic peptide hormone, consisted of eight amino acids, that mimics the activity of somatostatin, a natural hormone in the body. During the past decades, advanced instrumentation and crystallographic software established X-ray Powder Diffraction (XRPD) as a valuable tool for extracting structural information of biological macromolecules. The latter was demonstrated by the successful structural determination of octreotide at a remarkably high d-spacing resolution (1.87 Å) (PDB code: 6vc1). This study focuses on the response of octreotide to different humidity levels and temperatures, with a particular focus on the stability of the polycrystalline sample. XRPD measurements were accomplished employing an Anton Paar MHC-trans humidity-temperature chamber installed within a laboratory X’Pert Pro diffractometer (Malvern Panalytical). The chamber is employed to control and maintain precise humidity and temperature levels of samples during XRPD data collection. Pawley analysis of the collected data sets revealed that the octreotide polycrystalline sample is remarkably stable and no structural transitions were observed. The compound retains its orthorhombic symmetry (space group: P212121, a = 18.57744(4) Å, b = 30.17338(6) Å, c = 39.70590(9) Å, d~ 2.35 Å). However, a characteristic structural evolution in terms of lattice parameters and volume of the unit-cell is reported mainly upon controlled relative humidity variation. In addition, an improvement of signal-to-noise ratio in the XRPD data under a cycle of dehydration/rehydration is reported. These results underline the importance of considering the impact of environmental factors, as humidity and temperature, in the context of structure-based drug design, thereby contributing to the development of more effective and stable pharmaceutical products.

The Dph1•Dph2 heterodimer from yeast is a radical SAM (RS) enzyme that generates the 3-amino-3-carboxy-propyl (ACP) precursor for diphthamide, a clinically relevant modification on eukaryotic elongation factor 2 (eEF2). ACP formation requires SAM cleavage and atypical Cys-bound Fe-S clusters in each Dph1 and Dph2 subunit. Intriguingly, the first Cys residue in each motif locates next to another, ill-defined cysteine that we show in-here is conserved across eukaryotes. As judged from structural modeling, the orientation of these tandem cysteine motifs (TCM) suggests a candidate Fe-S cluster ligand role. Hence, we generated by site-directed DPH1 and DPH2 mutagenesis, Dph1•Dph2 variants with cysteines from each TCM replaced individually or in combination by serines. Assays diagnostic for diphthamide formation in vivo reveal that while single substitutions in the TCM of Dph2 cause mild defects, double mutations almost entirely inactivate the RS enzyme. Based on enhanced Dph1 and Dph2 subunit instability in response to cycloheximide chases, the variants with Cys substitutions in their cofactor motifs are particularly prone to protein degradation. In sum, we identify a fourth functionally cooperative Cys residue within the Fe-S motif of Dph2 and show that the Cys-based cofactor binding motifs in Dph1 and Dph2 are critical for the structural integrity of the dimeric RS enzyme in vivo.

Bamboo is considered a sustainable construction material due to its ability to grow quickly and its mechanical properties that are comparable to timber. Contributing to the current effort to establish the structural bamboo standards in the National Structural Code of the Philippines (NSCP), this study establishes the characteristic compressive strength of four bamboo species: Bambusa vulgaris (36 samples), Dendrocalamus asper (36 samples), Bambusa blumeana (94 samples), and Guadua angustifolia Kunth (30 samples). The samples were subjected to compressive loading following ISO 22157-1 (2017). The characteristic compressive strength values obtained, according to ISO 12122-1 (2014), were 40.35 MPa for B. vulgaris, 40.21 MPa for D. asper, 46.63 MPa for B. blumeana, and 36.99 MPa for G. angustifolia Kunth. Simple linear analysis, One-way ANOVA, and Welch’s t-Test were used to analyze the correlation models and establish a comparative analysis of the effect of nodes, and geometric and physical properties on the compressive strength of bamboos. Comparing the characteristic compressive strength obtained from this study to the strength of unseasoned structural timber of Philippine woods, all bamboo species showed higher strength values, and thus have great potential as an alternative construction material to timber.

Pseudomonas aeruginosa is an opportunistic pathogen that poses a significant threat to individuals with chronic respiratory ailments, such as cystic fibrosis (CF). The pathogen is highly prevalent in CF individuals and is responsible for chronic infection, resulting in severe tissue damage and poor patient outcome. However, early detection and immediate treatment are critical to prevent bacterial persistence and establishment of chronic infection. Presently, antibiotics including aminoglycosides, beta-lactams, polymyxins, and fluoroquinolones along with anti-inflammatory medications are being used to treat P. aeruginosa infections in CF patients. However, prolonged antibiotic administration has led to the emergence of widespread multidrug resistance in P. aeruginosa (CF isolates), contributing to antimicrobial resistance (AMR) and failure of antimicrobial therapies. Thus, exploring viable alternatives such as antivirulence therapeutics can be vital towards managing pseudomonal infections in CF patients and mitigating the risk of AMR. In this direction, antivirulence strategies achieving targeted inhibition of bacterial virulence pathways/factors, including quorum sensing, efflux pumps, lectins, and iron chelators, have been widely explored against CF isolates of P. aeruginosa. Simultaneously, there have been discussions about the sufficiency of in vitro findings and their successful translation in pulmonary infection models (in vivo) for the clinical implementation of antivirulence therapies hence, this review article presents a bird’s eye view on the pulmonary infections involving P. aeruginosa in CF patients by laying emphasis on factors contributing to bacterial colonization, persistence, and disease progression along with the current line of therapeutics against P. aeruginosa in CF while underscoring the limitation of antimicrobial approaches. We further collate scientific literature and comprehensively discuss the various antivirulence strategies that have been successfully tested against P. aeruginosa isolates from CF patients. This could pave the way towards a paradigm shift towards clinical therapy of pseudomonal infections in CF and can potentially override conventional antimicrobial treatments.

The infections caused by various bacterial pathogens both in clinical and community settings represent a significant threat to public healthcare worldwide. The growing resistance to antimicrobial drugs acquired by bacterial species causing healthcare-associated infections has already become a life-threatening danger noticed by the World Health Organization. Several groups or lineages of bacterial isolates usually called ‘the clones of high risk’ often drive the spread of resistance within particular species. Thus, it is vitally important to reveal and track the spread of such clones and the mechanisms by which they acquire antibiotic resistance and enhance their survival skills. Currently, the analysis of whole genome sequences for bacterial isolates of interest is increasingly used for these purposes, including epidemiological surveillance and developing of spread prevention measures. However, the availability and uniformity of the data derived from the genomic sequences often represents a bottleneck for such investigations. In this dataset, we present the results of a comprehensive genomic epidemiology analysis of 17,546 genomes of a dangerous bacterial pathogen Acinetobacter baumannii. Important typing information including multilocus sequence typing (MLST)-based sequence types (STs), intrinsic blaOXA-51-like gene variants, capsular (KL) and oligosaccharide (OCL) types, CRISPR-Cas systems, and cgMLST profiles are presented, as well as the assignment of particular isolates to nine known international clones of high risk. The presence of antimicrobial resistance genes within the genomes is also reported. These data will be useful for researchers in the field of A. baumannii genomic epidemiology, resistance analysis and prevention measure development.

The present study examined metabolites in Northern wild rice (WLD), the impact of WLD supplemented high fat (HF) diet on gut microbiota, short chain fatty acids (SCFAs) and correlation with metabolism or inflammation versus HF+white rice (WHR) in mice. C57BL/6J mice received HF diet supplemented with 26g% WHR, 26g% WLD, or 13g% WHR+13g% WLD (WTWD) for 12 weeks. The levels of fasting plasma glucose, total cholesterol, triglycerides, insulin resistance, inflammatory cytokines and monocyte adhesion were lower, and the abundances of fecal Lactobacillus gasseri species bacteria and propionic acid were higher in HF+WLD diet-fed mice compared to HF+WHR diet-fed mice (p<0.05). The anti-inflammatory effects of HF+WTWD diet were weaker than that in HF+WLD diet, but were greater than that in HF+WHR diet-fed mice (p<0.05). Relative abundances of fecal Lactobacillus gasseri and propionic acid in HF+WLD fed-mice were higher than that in HF+WHR fed mice. The abundance of fecal L. gasseri and propionic acid negatively correlated with metabolic and inflammatory markers (p<0.05). The findings suggest that WLD dose-dependently attenuated metabolic and inflammatory disorders in HF diet-fed mice. Interactions between WLD components and gut microbiota may upregulate fecal propionic acid and contribute to metabolic and anti-inflammatory benefits of WLD diet-induced insulin resistant mice.

The evidential value of an mtDNA match between biological remains and its potential donor is determined by the random match probability of the haplotype. This probability is based on the haplotype’s population frequency estimate. Consequently, implementing a population study representative of the population relevant to the forensic case is vital to correctly evaluating the evidence. The emerging number of poaching cases and the limited availability of such data emphasizes the need for improved fallow deer mtDNA population databank for forensic purposes, including targeting the entire mitochondrial control region. By sequencing the whole mitochondrial control region in 138 animals from five populations in Hungary we found four different haplotypes, including one which has not yet been described. Our results, supplemented with data already available from previous research do not support the possibility of determining the population of origin, although some patterns of geographical separation can be distinguished. Estimates of molecular diversity indicate approximately similarly low mtDNA diversity (Hd=0.565 and π = 0.002), compared with data from other countries. The calculated random match probability of 0.547 shows a high probability of coincidence and, therefore, a limited capacity for exclusion. Consequently, it may be necessary to search for polymorphic sites on other mitochondrial gene sections or to sequence the entire mitogenome of fallow deer.

Plant hormones regulate the adaptive responses to various biotic and abiotic stress factors. Applied exogenously they trigger the natural plant defense mechanisms, a feature that could be implemented in strategies for supporting crop resilience. The potential of exogenous cytokinin-like acting compound (kinetin), the auxin analogue 1-naphtyl acetic acid (NAA), abscisic acid (ABA) and the ethylene-precursor 1-aminocyclopropane-1-carboxylic acid (ACC) to mitigate dehydration was tested on Lactuca sativa (lettuce) grown on 12% polyethylene glycol (PEG). Priming with different blends containing these plant growth regulators applied in bioequivalent concentrations was evaluated through biometric measurements and biochemical analyses. The combined treatment with the four plant hormones exhibited the best dehydration protective effect. The antioxidative enzyme profiling of the PGR-primed individuals revealed increased SOD, catalase and peroxidase activity in the leaves. Immunodetection of higher levels of the rate-limiting enzyme for proline biosynthesis (delta-pyroline-5-carboxylate synthase) in the primed plants coincided with a significantly higher content of the amino acid measured in the leaves. These plants also accumulated particular dehydrin types, which may have contributed to the observed stress-relieving effect. The four-component hormonal mix applied by spraying or through the roots exerted similar stress-mitigating properties on soil-grown lettuce subjected to moderate drought.

Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism spectrum disorder, is caused by a full mutation (&gt;200 CGG repeats) in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene. Individuals with FXS experience a wide range of challenges related to social interaction (SI). Animal models, such as Drosophila melanogaster model for FXS where the only ortholog of human FMR1 (dFMR1) is mutated, have played a crucial role in understanding of FXS. The aim of this study was to investigate SI in the dFMR1B55 mutants using the novel Drosophila Shallow Chamber and a Python data processing pipeline based on social network analysis (SNA). In comparison with wild-type flies (w1118), SNA analysis in dFMR1B55 mutants revealed hypoactivity, fewer connections in their networks, a lower ability to efficiently transmit information, fewer alternative pathways for information transmission, a higher variability in the number of interactions they achieved, and tended to stay near the boundaries of the testing chamber. These observed alterations indicate the presence of characteristic strain-dependent social networks in dFMR1B55 flies, commonly referred to as the group phenotype. Finally, a combination of novel research tools is a valuable method for SI research in fruit flies.

Utilizing bioinformatics tools, this study expands our understanding of secondary metabolism in Botrytis cinerea, identifying novel genes within polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS), sesquiterpene cyclase (STC), diterpene cyclase (DTC), and dimethylal-lyltryptophan synthase (DMATS) families. These findings enrich the genetic framework associ-ated with B. cinerea's pathogenicity and ecological adaptation, offering insights into uncharted metabolic pathways. Significantly, the discovery of previously unannotated genes provides new molecular targets for developing targeted antifungal strategies, promising to enhance crop pro-tection and advance our understanding of fungal biochemistry. This research not only broadens the scope of known secondary metabolites but also opens avenues for future exploration into B. cinerea's biosynthetic capabilities, potentially leading to novel antifungal compounds. Our work underscores the importance of integrating bioinformatics and genomics for fungal research, paving the way for sustainable agricultural practices by pinpointing precise molecular interven-tions against B. cinerea. This study sets a foundation for further investigations into the fungus's secondary metabolism, with implications for biotechnology and crop disease management.

The continuous flowing spacetime forms a spacetime group G, one of its fundamental groups is the Poincare group PO(1,3), and the matter and interaction fields are representations of its intrinsic spacetime group. As a kind of quantized space-time unit, space-time group elements generate both space-time manifolds and matter. Matter and fields are aggregates of the quantum space-time within them and determine their type: the Lorentz group SO(1,3) represents a rotating spacetime corresponding to visible matter and the translation group P^1,3 represents a translational spacetime corresponding to dark matter and dark energy. The aggregation mode of space-time degrees of freedom in matter reveals that charge conjugation symmetry is the inverse symmetry of internal time of charged particles, and the external parity breaking of neutrinos is also due to their internal spatial aggregation mode.

BACKGROUND: Is pharmacovigilance at a moment of prominence for science and in relation to government responsibilities towards their nations, as the new coronavirus pandemic has surprised everyone in a negative and lethal way. OBJECTIVE: Evaluate pharmacovigilance as a resource for controlling and understanding the adverse effects caused by vaccines in use. DESIGN AND SETTING: Narrative review developed by a research group at Faculty of Medicine of the University of Porto. METHODS: This is a narrative review of the literature available in electronic media, government bulletins and similar bodies. The search was carried out using the descriptors: "Pharmacovigilance AND COVID-19 in Brazil", "Vaccine Development AND COVID-19 in Brazil", "Vaccination Hesitancy AND COVID-19 in Brazil", "Pharmacovigilance AND COVID-19", "Vaccine Development AND COVID-19", "Vaccination Hesitancy AND COVID-19", Pharmacovigilance AND COVID-19, Vaccine Development AND COVID-19, Vaccination Hesitancy AND COVID-19, "Public Health Surveillance AND COVID-19". In the period from May 2021 to June 2022. RESULTS: From the database search, 3 journal articles, 4 government bulletins and 535 scientific articles were identified. Of the total of 542 bibliographic materials, 36 were selected according to the selection criteria and objectives of the study. CONCLUSIONS: The vaccines in use have proven efficacy, despite adverse reactions that cannot be attributed solely and exclusively to their use, since the medical history of each patient should be considered in the investigation of each case, especially when there is death. The Brazilian data for adverse events, although the country is continental in its size, are acceptable given the number of deaths recorded.

The inherited ‘EIA’ process at Brexit is based on a ‘Project’ period from Inception tothe start of construction works. The ‘Incompleteness’ of the process covers andidentifies stages that will impact on the environmental cycle: construction period,operational life, de-commissioning and a return to acceptable environmental footprint.A master environment structure-plan framework is required to commence with theupgrading of the complete ‘EIA’ process, embracing separate limbs for the UK’spriority environmental targets for climate change, and other major adverse effectswhich result in serious ‘harm’ to the UK environment. The identification of the processfor ‘incompleteness’ requires effective sustainability, and inclusion of effectivemanagement tools, for the essential ‘monitoring/control/recording’ proceduresthroughout the project life and the natural environmental cycle. This will allow theopportunity for a new approach to a structured ‘Suite of EIAR Directives’, to enable a‘EIAR’ regime that ‘will remain fit and proper for UK purpose’.

In recent decades, there have been numerous endeavors to develop a novel category of survival distributions possessing enhanced flexibility through the extension of existing distributions. This article constructs and validates the statistical properties of a novel survival distribution in order to obtain an alternative distribution that is suitable for analyzing survival data by presenting the novel mixture of the Fréchet distribution along with statistical properties such as the probability density function (PDF), cumulative distribution function (CDF), rth ordinary moment, skewness, kurtosis, moment-generating function, mean, variance, mode, survival function, hazard function, and asymptotic behavior, as well as constructing the estimators of the unknown parameter by employing the expectation-maximization (EM) algorithm, and simulated annealing. Additionally, the performance of the proposed estimators was compared with bias, mean squared errors (MSE), and simulated variances, and given an illustrative example of the proposed distribution to the survival data set in order to show that the proposed distribution is appropriate for the right-skewed data. This will be extremely advantageous in survival analysis.

In the era of big data with increasingly complex data structures and ever-larger data scales, matrix-type data are becoming highly valued and their applications in the fields of medicine, industry, education, geography, and astronomy are growing in extent. In recent years, significant progress has been made in the practical use of matrix variable t-distribution finite mixture models for handling data in order to address the issues of multi-subgroup structures and long data tails. In this paper, the expectation-maximization (EM) algorithm with penalized maximum likelihood is proposed to resolve the problem of the unbounded nature of the likelihood function applied to the model by considering the degeneracy of the variance-covariance matrix of this model. Our data were analyzed through simulations and real data, and the results demonstrate that our model is effective in both preventing the likelihood function from being unbounded and in ensuring the accuracy of the estimated parameters of the EM algorithm.

German chamomile (Matricaria chamomilla L.) is an essential oil-content medicinal plant widely used worldwidely. The aim of this study was (1) to gain knowledge of the phytochemical composition and the analgesic and soporific activity of M. chamomilla flowers extract and its amino acid preparations, (2) to predict the mechanisms of their effects by molecular docking, and (3) to develop aqueous printing gels and novel 3D-printed oral dosage forms for M. chamomilla flowers extracts. In total 22 phenolics and 14 amino acids were identified and quantified in the M. chamomilla extracts. The in-vivo animal studies with rodents showed that the oral administration of such extracts revealed the potential for treating of sleep disorders and diseases accompanied by pain. Amino acids were found to potentiate these effects. Glycine enhanced the analgesic activity the most, while lysine and β-alanine improved the soporific activity. The molecular docking analysis revealed a high probability of GABAA and NMDA receptor antagonism and COX-1,2 inhibition by the extracts. A polyethylene oxide (PEO) based gel composition with the M. chamomilla extracts were proposed for preparing a novel 3D-printed dosage form for the oral administration. These 3D-printed extract preparations can be used for example in dietary supplement applications.

My innovative entropy measure, Ismail entropy, namely, (IE) is an ultimate generalization to numerous generalized entropies within the literature. The fractal dimension of IE is identified in this paper. On another applicative note, this paper offers some potential applications of fractal dimension to smart cities. The paper ends with closing remarks combined with some challenging open problems and the next phase of research.

Background. Azithromycin (AZM) is widely used in cystic fibrosis (CF) treatment following clinical trials demonstrating improved lung function and fewer pulmonary exacerbations. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF macrophages. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. Methods: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs) were differentiated into monocyte-derived macrophages (MDMs) and infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. Results: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected, however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM did not restore endocytosis in CF, another essential feature of M2 macrophages. Conclusions: This study highlights the cellular functions and molecular targets of AZM which may involve improved uptake of both gram-positive and gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.

Dyadic data which is also called co-occurrence data (COD) contains co-occurrences of objects. Searching for statistical models to represent dyadic data is necessary. Fortunately, finite mixture model is a solid statistical model to learn and make inference on dyadic data because mixture model is built smoothly and reliably by expectation maximization (EM) algorithm which is suitable to inherent spareness of dyadic data. This research summarizes mixture models for dyadic data. When each co-occurrence in dyadic data is associated with a value, there are many unaccomplished values because a lot of co-occurrences are inexistent. In this research, these unaccomplished values are estimated as mean (expectation) of random variable given partial probabilistic distributions inside dyadic mixture model.

As the rapid development of communication industry, especially the 5G communication and IOT, there will be plenty of electromagnetic (EM) waves in the free space, which carry lots of energies. However, some of these energies are wasted in free space. To reuse these wasted energies, significantly growing interests are towards to the energy harvesting antennas. This paper is aimed to investigate a wearable antenna which can transfer RF energy from ambient sources to direct current by a soft and portable textile antenna. Among the numerous signals in mobile network, the GSM 1800, 3G, WiFi and 4G/5G will be chosen due to the city signal intensity distribution. Hence, a corresponding triple bands antenna has been designed to cover those frequency bands. The CST STUDIO SUITE is used in whole process of antenna design and simulation. The proposed antenna is a hooked dipole antenna with tuning bar (HATB) whose ends have small folded part in each side for better bandwidth performance. The presented antenna provides a wide operating band from 1.8 GHz to 2.5 GHz below -10 dB in return loss. And methods to overcome interference between antennas is found. Furthermore, using the corresponding rectifier to achieve the RF/DC conversion. The overall efficiency of whole rectifier is about 56.8 %, and output power level of the antenna system is 45.92nW. The experimental results could indicate that my textile hooked antenna harvester is a good choice for the charging system of personal wearable attachment, which could achieve low power absorbing for long distance anytime and anywhere.

Natural Gas (NG) processing is a prominent industrial separation process. Among the available techniques, the innovative membrane process shows potential for efficient removal of impurities, including carbon dioxide (CO₂). This study focuses on utilizing breakthroughs in membrane separation to drive sustainable CO₂ extraction from natural gas. Through comprehensive research and analysis, we explore the effectiveness and feasibility of membrane-based systems in removing CO₂ impurities from NG, thus promoting greener and more sustainable industrial practices. Our findings underscore the transformative nature of membrane separation technology, presenting new possibilities for a more environmentally-friendly and sustainable approach to CO₂ extraction from natural gas.Natural Gas (NG) processing utilizes various techniques for impurity removal, with the membrane process emerging as a promising option for efficient carbon dioxide (CO₂) extraction. This research proposes the integration of a simple mathematical model into ASPEN HYSYS to design a membrane system for CO₂/CH₄ separation. The study also investigates parameter sensitivities by altering operating conditions, such as feed composition and pressure, as well as membrane properties, including selectivity. By analyzing these variables, we aim to optimize the performance and efficiency of the membrane system, facilitating the sustainable extraction of CO₂ from NG. The findings contribute to advancing the design and operation of membrane-based processes for CO₂ separation, paving the way for greener and more sustainable industrial practices. In addition, this study explores various configurations for optimizing the design of the membrane system, including single-stage with and without recycling as well as double-stage configurations. The investigation demonstrates that methane recovery can be enhanced through the recycling of the permeate stream and by implementing a double stage membrane system. These findings highlight the potential for improving the efficiency and performance of the membrane system, enabling higher methane recovery rates. By considering different configurations, this research contributes to the development of more effective and sustainable CO₂ extraction processes from natural gas.

Very disparate types of cell populations exhibit similar transcription specificity for certain genes. We identified 20 genes that were expressed preferentially in myoblasts and cerebellum (Myob/Cbl genes) and examined their cell/tissue-specific epigenetics using a combined approach of comparing DNA methylation, chromatin accessibility, and RNA expression in many different cell populations. Some Myob/Cbl genes shared DNA hypo- or hypermethylated regions in myoblasts and cerebellum. Particularly striking was ZNF556, whose promoter is hypomethylated in expressing cells but highly methylated in the many cell populations that do not express the gene. In reporter gene assays, we demonstrated that its promoter’s activity is methylation-sensitive. The atypical epigenetics of ZNF556 may have originated from its promoter’s hypomethylation and selective activation in sperm progenitors and oocytes. Five of the Myob/Cbl genes (KCNJ12, ST8SIA5, ZIC1, VAX2, and EN2) have much higher RNA levels in cerebellum than in myoblasts and displayed myoblast-specific hypermethylation upstream and/or downstream of their promoters that may downmodulate expression. Differential DNA methylation was associated with alternative promoter usage for Myob/Cbl genes MCF2L, DOK7, CNPY1, and ANK1. Myob/Cbl genes PAX3, LBX1, ZNF556, ZIC1, EN2, and VAX2 encode sequence-specific transcription factors, which likely help drive the myoblast and cerebellum specificity of other Myob/Cbl genes. Our study extends our understanding of epigenetic/transcription associations related to differentiation and may help elucidate relationships between epigenetic signatures and muscular dystrophies or cerebellar-linked neuropathologies.

Tick-borne encephalitis virus (TBEV) is a RNA-containing enveloped virus, a member of the Flaviviridae family. Here we describe a detailed analysis of the size and structure of inactivated TBEV (the Sofyin-Chumakov TBEV strain, used in vaccines). Four analytical methods were used to analyze individual TBEV particles—negative staining TEM, cryo-EM, AFM, and NTA. All methods confirmed that the particles were monodisperse, and their mean size was ~50 nm. Cryo-EM data were used to obtain a 3D electron density model of the virus with clearly distinguishable E-proteins. STEM-EELS analysis detected phosphorous in the particles, which was interpreted as the RNA signal. Altogether, the described analytical procedures can be valuable for the further analysis of vaccine inactivated virus samples.

The presence of potentially pathogenic bacteria on veterinary clinic surfaces may be problematic. In this study we collected swab samples (Fisherbrand, double transport swabs with Stuart’s liquid medium) and water samples from five veterinary rehabilitation clinics. Swabs and water samples were transported to a microbiology lab for processing. At the lab swabs were used to inoculated Hardy’s Cdiff Banana broth (for Clostridium difficile [Cdiff]), and five different types of bacterial growth media, including: Hardy CHROM MRSA agar (methicillin resistant Staphylococcus aureus [MRSA], and S. pseudintermedius [SIM]), Mannitol Salt Agar (S. aureus), Eosin Methylene Blue agar (enterics [ENT]), Pseudomonas Isolation agar (Pseudomonas sp.), and Tryptic Soy Agar [TSA] (non-specific). The most prominent species cultured was Cdiff (on nearly 55% of swabs). Bacillus sp. and Enterics were encountered on nearly 35% of swabs, with MRSA and SIM on just over 10% of swabs. The most contaminated sample site was harnesses/life jackets used with the underwater treadmill (33% of swabs). Underwater treadmill water had total bacterial counts from 1.6 to 2.7 e3 cfu/ml. Of all bacterial species detected SIM tends to be more pathogenic for dogs. Targeted cleaning/disinfecting in these clinics could help reduce risks for both animals and caregivers utilizing these clinics.

This literature review aims to gain a deeper understanding of Spinosaurus aegyptiacus’s dorsal sail regarding its function as thermoregulation, display, or hydrodynamic. The function of S. aegyptiacus’s dorsal sail has been widely debated for many years. The three most popular hypotheses are that it was used as a biological mechanism of thermoregulation, display, or hydrodynamic. The display hypothesis includes attracting mates, intimidating rivals, and social communication with other members. This literature review delves into each of the three hypotheses using past studies and excavation sites to analyze their validity. For the hydrodynamic aspect, the lifestyle of S. aegyptiacus must first be established. Based on existing research, we cannot conclude that there is a definitive primary function of Spinosaurus aegyptiacus’s dorsal sail. However, it is likely that its sail served the crucial function of display, since it would have a large surface area and could thus be a distinguishable characteristic of S. aegyptiacus that could determine mating success. Additionally, it is probable that the sail had supplementary roles in thermoregulation and hydrodynamics.

Escherichia coli is an indicator microorganism in One Health antibiotic resistance surveillance programmes. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole genome sequencing (WGS). Porcine E. coli isolates were proportionally more resistant phenotypically and harboured a richer diversity of antibiotic resistance genes, as compared to human E. coli isolates. Different pathovars, namely ExPEC (12.43%, 21/169), ETEC (4.14%; 7/169), EPEC (2.96%, 5/169), EAEC (2.96%, 5/169) and STEC (1.18%, 2/169) were detected at low frequencies. Sequence type complex (STc) 10 were the most prevalent (85.51%, 59/169) among human and porcine isolates. Six STcs (STc10, STc86, STc168, STc206, STc278 and STc469) were shared at the human-livestock interface according to multilocus sequence typing (MLST). Core genome MLST and hierarchical clustering (HC) showed that human and porcine isolates were overall genetically diverse, but some clustering at HC2 to HC200 were observed. In conclusion, even though the isolates shared a spatio-temporal relationship, there were still differences in the virulence potential, antibiotic resistance profiles, and cgMLST and HC according to the source of isolation.

The identification of a new virus Kiparis-144 (KiparisV) in a half-fed tick I persulcatus, removed from a person in the south of the Russian Far East, determined the goal of further research - to study its role in human pathology and the characteristics of its behavior in the tick microbiome. An ELISA study of 439 blood samples from people affected by tick bites indicated a fairly frequent (up to 16.4±1.7%) encounter of people with the KiparisV virus in the territory of natural foci of the Primorsky Territory. It has been shown that this virus, when mono-infected, can cause clinical symptoms characteristic of acute respiratory diseases. During co-infection under the influence of the KiparisV, there was an increase in the activity of Borrelia spp. with the constant production of antibodies to them only of the IgM class and clinical symptoms of Lyme disease for one year (observation period). Electron microscopy of the KiparisV found in a tick removed from a patient showed a picture of the relationship of the KiparisV (up to 100 nm in size) with unknown representatives of the tick microbiome - pathogens of a viral or bacterial nature. In a comparative aspect, a similar electron microscopic picture of the interaction of the KiparisV virus with a known pathogen of viral nature, the ectromelia virus (ECTV), is presented. The importance of the electron microscopy method in describing the tick microbiome is shown. Thus, it has been established that when co-cultivated in the system the helper-virus KiparisV probably tends to use another pathogen of the tick microbiome for its reproduction, influencing its pathogenicity.

a Special Issue of Microorganisms devoted to ‘Microbial Biocatalysis and Biodegradation’ would be incomplete without some form of acknowledgement of the many important roles that dioxygen-dependent enzymes (principally mono- and dioxygenases) play in relevant aspects of biooxygenation. This is reflected by the multiple strategic roles that dioxygen -dependent microbial enzymes play both in generating valuable synthons for chemoenzymatic synthesis, and in facilitating key reactions that drive the global geochemical Carbon Cycle. A useful insight into this relationship can be gained by reviewing the evolution of the current status of 2,5-diketocamphane 1,2-monooxygenase (EC 1.14.14.108) from camphor-grown Pseudomonas putida ATCC 17453. Over the last sixty years, the perceived nature of this monooxygenase has transmogrified significantly. Commencing in the 1960s, extensive initial studies consistently reported that the enzyme was a monomeric true flavoprotein dependent on both FMNH₂ and nonheme iron as bound cofactors. However, over the last decade all those criteria have changed absolutely, and the enzyme is currently acknowledged to be a metal ion-independent homodimeric flavin-dependent two-component monooxygenase deploying FMNH₂ as a cosubstrate. That transition is a paradigm of the ever evolving nature of scientific knowledge.

Air pollution, climate change and global warming show direct linkage. Introduction - Background: Research in the field has proposed and demonstrated their link to increased allergenicity in plants, leading to increased allergic diseases. Allergen patterns are changing in response to climate change. Across Europe, up to 12% of the population suffers from allergic diseases (bronchial asthma and allergic rhinitis) caused by the pollen grains. The medical costs of these types of allergies are enormous and are increasing with the spread of common ragweed - Ambrosia artemisiifolia* in Europe. In practice, more and more patients are turning to allergists. Methods: Based on these data, the research aims to identify safety measures and specific legislation to control and eradicate common ragweed in the countries most affected by the spread of this plant in Europe, increase in population exposure in countries affected by the presence of common ragweed and the socio-economic impact of allergic rhinitis and bronchial asthma at European level.[1][2] Our database search did not reveal any other research that has addressed this topic to date. Results: This research identifies specific legislation to the countries most affected by the spread of this plant pollen grains at European level, changes in allergen patterns and monitoring/safety eradication measures decided by local authorities, and data on the spread of common ragweed over the last two decades, costs per treatment, increased allergic rhinitis and bronchial asthma morbidity in the most affected areas. Conclusions: At European level, there are no universally valid models for eradicating this weed. Various methods can be used to limit the spread of common ragweed and its pollen production (e.g. mowing once or twice a year of overgrown land, ploughing, chemical control, public information, etc.). Local and regional cooperation should be considered essential to promote phytosanitary &amp; safety measures and exchange of information on methods to identify and manage the spread of common ragweed. Unified legislation at European level would help all affected countries; reduce morbidity from respiratory allergic diseases and the costs of treating these diseases.

This study explores the evolution of price-to-book (P/B) ratios among European banks from 2005 to 2020, period where the majority of banks in different countries had a P/B ratio below 1. By dissecting banks' accounting equity into investor contributions and earnings-derived components, the research aims to evaluate how each component of equity affects these ratios and investigates whether their dynamics shifted during the period. We address a gap in prior research that has not extensively examined how individual equity components affect the overall P/B ratio. This aspect is crucial, especially in scenarios where the increase of specific components compensates for declines in others, thereby stabilizing total equity values. Our methodology involves regression analyses using a panel data model with random effects. The findings reveal that earnings-related equity components significantly influence P/B ratios. In contrast, investor contributions; which strengthen the solvency of the entity, appear to have a minimal impact. Additionally, our analysis highlights a significant quadratic relationship between the P/B ratios and both the profit or loss reported on Income Statements and distributed dividends.

This study aimed to characterize the long non-coding RNA (lncRNA) expression in the bovine mammary gland and to infer their functions in dietary response to 5% linseed oil (LSO) or 5% safflower oil (SFO). Twelve cows (six per treatment) in mid lactation were fed a control diet for 28 days followed by a treatment period (control diet supplemented with 5% LSO or 5% SFO) of 28 days. Mammary gland biopsies were collected from each animal on day-14 (D-14, control period), D+7 (early treatment period) and D+28 (late treatment period) and were subjected to RNA-Sequencing and subsequent bioinformatics analyses. Functional enrichment of lncRNA was performed via potential cis regulated target genes located within 50 Kb flanking regions of lncRNAs and having expression correlation of >0.7 with mRNAs. A total of 4955 lncRNAs (325 known and 4630 novel) were identified which potentially cis targeted 59 and 494 genes in LSO and SFO treatments, respectively. Enrichments of cis target genes of lncRNAs indicated potential roles of lncRNAs in immune function, nucleic acid metabolism and cell membrane organization processes as well as involvement in Notch, cAMP and TGF-β signaling pathways. Thirty-two and 21 lncRNAs were differentially expressed (DE) in LSO and SFO treatments, respectively. Six genes (KCNF1, STARD13, BCL6, NXPE2, HHIPL2 and MMD) were identified as potential cis target genes of six DE lncRNAs. In conclusion, this study indicated potential roles for lncRNAs in mammary gland immune functions and development and provided potential candidate genes and pathways via which lncRNAs can function in diet responses.

Several effective online and offline inference tools offer an interactive platform for inference, visualization, and analysis of gene regulatory networks. However, a tool currently needs to offer a scalable, lightweight, integrated online platform for carrying out inference, visualization, benchmarking, and extensive network analysis in an integrated manner. We introduce NetRA (Network Reconstruction and Analysis for Gene Regulatory Network), a comprehensive web tool for network analysis, visualization, and inference of large expression networks. Additionally, a platform for benchmarking and evaluation is provided. In order to deliver a highly scalable, lightweight, and rich user interface, the tool is created using the most recent technologies. We incorporate the original code of eleven (11) inference algorithms (not limited to) from Bioconductor in the current version. We also report a qualitative comparison of 11 candidate methods regarding prediction accuracy and network characteristics which will shed light on their performance against 4000 sizes synthetic DREAM network. We believe the tool will significantly aid biologists' downstream system biology research. NetRA tool can be extensible to different kinds of complex network analyses. Availability: On request ([email protected]).

Genes encoding regulatory RNAs known as short RNAs (sRNAs) or non-coding sRNAs (ncRNAs), modulate physiological responses through different mechanisms, through RNA-RNA interaction or RNA-protein interaction. These molecules transcribed in trans and in cis relative to the target RNA. They are located between the coding regions of proteins, i.e., in the intergenic regions of the genome and show signals of promoters and termini sequences generally Rho-independent. The size of the ncRNAs genes ranges from ~ 50 to ~ 500 nucleotides and several transcripts are processed by RNase with smaller end products, which modulate physiological responses through different mechanisms, by RNA-RNA interaction or RNA-protein interactions and some interactions may be stabilized by the Hfq chaperone. The Riboswitches constitute another class of ncRNAs, located in the 5'UTR region of an mRNA that promote transcriptional regulation through their interaction with a linker molecule. Recently, in prokaryotes, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) regions have described, which repeats of sequences of palindromic bases are. Each replicate consists of short segments of "spacer DNA" from exposures prior to a bacteriophage virus or exogenous plasmid. The CRISPR system consists of an immune system of resistance to exogenous molecules.

Abstract: Objective: analyze the effectiveness of the implementation of the Lean Healthcare sys-tem at the emergency room of the Clinical Hospital of the Federal University of Uberlândia (HC-UFU), based on a comparison of hospital indicators obtained over the three phases corre-sponding to the period of one year before the implementation (T1), the year during the imple-mentation (T2) and one year after implementation (T3). Material and Methods: this is applied research, classified as a case study, exploratory, descriptive that is developed in stages. Based herein on the search for hospital indicators, as occurred in the implementation process of Lean in Emergencies at the HC-UFU and a description of the implemented Lean system. Results and Discussions: during the period where it was possible to collect data relevant to the NEDOCS and LOS indicators, the motivation of the teams grew, but with a notable tension between municipal management and hospital management. It was found that, despite the fluctuations, the patient length of stay in the Emergency Room remained high. Noteworthy here is that with the excep-tion of the variable of female deaths before 24 hours of hospitalization, all other variables showed percentage increases before and after the intervention. Conclusion: the methodology followed for the implementation of Lean in Emergencies in the emergency sector of the hospital did not produce an improvement in hospital indicators.

Centrifugal pumps are widely employed in the oil refinery industry due to their efficiency and effectiveness in fluid transfer applications. The reliability of pumps plays a pivotal role in ensuring uninterrupted plant productivity and safe operations. Analysis of failure history data shows that bearings have been identified as critical components in oil refinery pump groups. However, traditional reliability estimation theories may not apply when data is limited or subject to right censoring. This paper addresses the complexity of estimating the Weibull distribution parameters using the maximum-likelihood method under the abovementioned conditions. The likelihood equation lacks an explicit analytical solution, necessitating the use of numerical methods for resolution. The proposed approach presented in this article leverages the Expectation-Maximization (EM) algorithm for estimating the Weibull distribution parameters. This method provides more accurate estimates of failure rates and probabilities by accounting for limited and censored data. The findings are demonstrated through a case study, showcasing the practical application of the proposed approach.

Expectation maximization (EM) algorithm is a powerful mathematical tool for estimating statistical parameter when data sample contains hidden part and observed part. EM is applied to learn finite mixture model in which the whole distribution of observed variable is average sum of partial distributions. Coverage ratio of every partial distribution is specified by the probability of hidden variable. An application of mixture model is soft clustering in which cluster is modeled by hidden variable whereas each data point can be assigned to more than one cluster and degree of such assignment is represented by the probability of hidden variable. However, such probability in traditional mixture model is simplified as a parameter, which can cause loss of valuable information. Therefore, in this research I propose a so-called conditional mixture model (CMM) in which the probability of hidden variable is modeled as a full probabilistic density function (PDF) that owns individual parameter. CMM aims to extend mixture model. I also propose an application of CMM which is called adaptive regressive model (ARM). Traditional regression model is effective when data sample is scattered equally. If data points are grouped into clusters, regression model tries to learn a unified regression function which goes through all data points. Obviously, such unified function is not effective to evaluate response variable based on grouped data points. The concept “adaptive” of ARM means that ARM solves the ineffectiveness problem by selecting the best cluster of data points firstly and then evaluating response variable within such best cluster. In order words, ARM reduces estimation space of regression model so as to gain high accuracy in calculation.

Corona viruses hijack human enzymes to assembly sugar coat on Spike glycoproteins. The mechanism that human antibodies may uncover the antigenic viral peptide epitopes hidden by sugar coat are unknown. In this study, we analyzed recombinant SARS-CoV-2 Spike protein secreted from BTI-Tn-5B1-4 cells, by trypsin and chymotrypsin digestion followed by mass spectrometry analysis. We acquired MS/MS spectrums for glycopeptides of all 22 predicted N-glycosylated sites. We further analyzed the surface accessibility of Spike proteins according to Cryo-EM and homolog-modeled structures, and available antibodies that bind to SARS-CoV-1. The results showed that all 22 N-glycosylated sites of SARS-CoV-2 are modified by high-mannose type of N-glycans. MS/MS fragmentation clearly established the glycopeptide identities. Electron densities of glycans cover most of the Spike receptor binding domain of SARS-CoV-2, except YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ, similar to a region FSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQ in SARS-CoV-1. Other surface-exposed domains included those located on Central Helix, between amino acids 967 and 1016 of SARS-CoV-1, and 985 to 1034 of SARS-CoV-2 Spike protein. As the majority of antibody paratopes bind to peptide portion with or without sugar modification, we propose a snake-catcher model that a minimal length of peptide is first clamped by a paratope, and the binding is either strengthened by sugars close to peptide, or not interfered by sugar modification.

Giant plasmonic surface enhancement has been observed in gold coated micron sized inverse pyramids entrapping a gold nanoparticle. The amplification of both surface enhanced Raman and photoluminescence signals was found to be dependent on the diameter of trapped gold nanoparticle and around 50-fold enhancement was detected for 250nm diameter sample relatively to the 50nm one. Finite differential time domain simulations, performed to determine the near-field distribution in the structure, showed that when the nanoparticle protrudes into the hotspot zone of the void, coupling of electromagnetic field occurs and the plasmon-related near-field enhancement is concentrated into the close vicinity of the nanoparticle, mainly into the close gaps around the tangential points of the curved sphere and the flat pyramid surface. This results in a more than 15 times increase of the near-field intensity, compared to the empty void.

Phospholipases are among the important elements involved in lipid-dependent cell signaling that lead to the induction of downstream pathways. In the current study, phospholipases D (PLDs) gene family was characterized and compared in two important oilseeds crops, Brassica napus and Camelina sativa. The results revealed that PLD has 33 members in Camelina sativa (CsPLD) and 41 members in Brassica napus (BnPLD). All studied PLDs showed a negative GRAVY value, indicating that PLDs are probably hydrophilic proteins. Phylogenetic analysis separated PLDs into five subfamilies; gamma, delta, beta, alpha, and zeta. According to evolution analysis, a different evolution process was observed between CsPLD and BnPLD. In addition, the results disclosed that the most of the PLD genes have been segmentally duplicated under purifying selection. Cis-regulatory elements related to ABA and auxin responsiveness were more found in upstream region of CsPLDs, while elements linked with MeJA responsiveness were more dis-tributed in promoter region of BnPLDs. Analysis of the expression data showed that PLD alpha genes have a wide expression and are expressed in most tissues. Quantitative expression analysis (qPCR) of CsPLD genes under salt stress, 200 mM of NaCl, was done in different time series. The results revealed that the CsPLD genes are involved in the response to salinity stress and their expression levels enhance with the increase of salinity stress time. The outcomes of this research will be useful for future molecular work related to lipid signaling in oilseed plants.

Retinitis pigmentosa-59 (RP59) is a rare, recessive form of RP, caused by mutations in the gene encoding DHDDS (dehydrodolichyl diphosphate synthase). DHDDS forms a heterotetrameric complex with Nogo-B Receptor (NgBR; gene NUS1) to form a cis-prenyltransferase (CPT) enzyme complex, which is required for synthesis of dolichol, which in turn is required for protein N-glycosylation as well as other glycosylation reactions in eukaryotic cells. Herein, we review the published phenotypic characteristics of RP59 models extant, with an emphasis on their ocular phenotypes, based primarily upon knock-in of known RP59-associated DHDDS mutations as well as cell type- and tissue-specific knockout of DHDDS alleles in mice. We also briefly review findings in RP59 patients with retinal disease and other patients with DHDDS mutations causing epilepsy and other neurologic disease. We discuss these findings in the context of addressing “knowledge gaps” in our current understanding of the underlying pathobiology mechanism of RP59, as well as their potential utility for developing therapeutic interventions to block the onset, or to dampen the severity or progression, of RP59.

Polymer-based (nano)composite foams, especially those having a microcellular structure, containing suitable conductive (nano)fillers, have been shown to act as good shielding materials, hence coming as promising to act as shields in electronic devices, limiting/avoiding electromagnetic interference (EMI) pollution. Nevertheless, due to their high (micro)structural complexity, related to their multiphase nature, there is still a lot of unawareness behind the shielding mechanisms acting in these materials, coming as a necessity to study their microstructure-cellular/porous structure-properties relations, especially in terms of their electrical conductivity and EMI shielding efficiency (EMI SE). To target and control the electrical conductivity through a controlled distribution/dispersion of conductive nanofillers, single or combined (nanohybrids), as there is a direct relation between electrical conductivity and EMI SE, as well as the main EMI shielding mechanisms working on the developed microcellular structure of the foams, which are expected to be absorption-dominated or absorption/multiple reflection-based, are two of the main objectives when combining polymer foaming with the addition of conductive nanofillers. The present review work considers the recent developments and trends on polymer-based foams containing conductive nanofillers, especially carbon-based such as carbon nanotubes or graphene-based materials, as well as similar porous structures created using trending technologies such as 3D printing, for EMI shielding applications. It is divided in different sections, starting with the strategy of microcellular foaming to develop polymer-based foams with enhanced EMI shielding characteristics, especially focusing on technologies and methods using supercritical CO2 (sCO2); continuing with the use of polymer foams as templates to synthesize carbon foams with improved EMI shielding performance for high use temperature applications; the recent strategy of combining different functional (nano)fillers to create hybrid nanofillers/nanohybrids to be used at lower amounts as conductive fillers in polymer foams; the control and selective distribution of the nanofillers in terms of favoring the formation of a more effective conductive network and hence promote the enhancement of the EMI SE; the very recent use of computational approaches to tailor the EMI shielding properties of composite foams; and the very trending possibility of creating cellular components with varied porous structures from these materials using 3D printing; to finish, some future perspectives are discussed.

To follow the growth and development of each tree (N = 1200) Pinus sylvestris L., var. Negorelskaya starting from the seed and continuing at the juvenile (or even generative) stage is the goal of an ambitious project to create a plant passport if possible. Five datasets of replenished empirical (tab-ular and file) and systematic data reflect the early results of a unique ongoing experiment conducted with families moved along a climatic gradient from the collection area (1731 degree days, 722 mm) to the experimental area (2326 degree days; 786 mm). Datasets of morphometric, VIS-spectrometric, and germination seed data, combined with the first results of biometric data (including the Dickson quality index) of seedlings produced from these seeds, will allow scientists in the future to conduct correlation and other statistical analysis, or train a neural network to determine the presence of connections between a seed and a plant. These data contribute to the early non-destructive diag-nosis and grading of seeds according to VIS-spectrometric properties. This dataset structure can complement the FLR-Library. In the future, by tracing seedlings in their early growth (for example, over three growing seasons at the site being restored), it will be possible to determine the degree of intensification of FRM production depending on the initial properties of the seed.

Blockchain technology can achieve decentralization, multi-party verification, anti-tampering, anonymity, traceability of transactions, and the application of distributed ledger. Countries around the world continue to seek the blockchain business models, technologies and applications, and have different visions and policies for the development of blockchain. This study conducts a comparative policy framework of theoretical analysis of the blockchain technology between the USA and China. Using the innovative policy tools proposed by Rothwell and Zegveld, the above mentioned governments are analyzed from the viewpoint of twelve policy tools. The results show that the USA and China all prefer to use “Environmental-side” policy. The USA has paid more attention to “Legal and regulatory”, “Public services” and “Procurement”. China has the highest proportion of policies in “Political tools”, followed by “Legal & regulatory”, while “Scientific and technical”, “Education” and “Overseas agent” come in third . The blockchain technology has developed vigorously among industries and its applications have gradually diversified. The results are provided to various stakeholders as a reference for policy planning.

The aim of this study was to investigate the role of DNA methylation in the regulation of in vitro and in vivo cartilage formation. Based on the data of an RNA chip-assay performed on chondrifying BMP2-overexpressing C3H10T1/2 cells, the relative expression of Tet1 (tet methylcytosine dioxygenase 1), Dnmt3a (DNA methyltransferase 3) and Ogt (O-linked N-acetylglucosamine transferase) genes was examined with RT-qPCR in mouse cell-line based and primary micromass cultures. RNA probes for in situ hybridization were used on frozen sections of 15-day-old mouse embryos. DNA methylation was inhibited with 5-azacytidine during culturing. We found very strong but gradually decreasing expression of Tet1 throughout the entire course of in vitro cartilage differentiation along with strong signals in the cartilaginous embryonic skeleton. Dnmt3a and Ogt expressions did not show significant changes with RT-qPCR and gave weak in situ hybridization signals. Inhibition of DNA methylation applied during early stages of differentiation reduced cartilage-specific gene expression and cartilage formation. In contrast, it had stimulatory effect when added to differentiated chondrocytes. Our results indicate that the DNA demethylation-inducing Tet1 is a significant epigenetic factor of chondrogenesis, and inhibition of DNA methylation exerts distinct effects in different phases of in vitro cartilage formation.

This study presents a comprehensive assessment of indoor particulate matter (PM) concentrations, focusing on PM1, PM2.5, and PM10 in five Primary Health Centers (PHCs): Arakale, Federal College of Agriculture (FECA), Iju, Oba-Ile, and Owode within Akure Local Government Areas in Nigeria. The primary novelty of this research lies in its detailed exploration of the toxicity potential of these PM fractions, providing valuable insights into the local air quality and associated health risks. The study assesses the health implications by calculating the toxicity potential (TP), Relative Risk (RR), Excess Risk (ER), and Attributable Fractions (AF) for cardiopulmonary and lung cancer mortality. The results reveal varying RR values for all-cause mortality, with Arakale showing a slight elevation (RR: 1.061), indicating potential health risks. ER values for cardiopulmonary mortality range from 14.728±7.25 to 19.04±0.38, emphasizing the substantial excess risk associated with long-term PM2.5 exposure. The study also uncovers AF for cardiopulmonary mortality ranging between 11.03±0.31 to 19.22±0.04, underscoring the significant contribution of PM to cardiovascular and respiratory health risks. Similarly, AF for lung cancer mortality ranges from 10.03±0.012 to 17.13±0.10, highlighting the substantial association between PM2.5 exposure and lung cancer risk. These findings underscore the urgent need for targeted air quality management strategies and public health interventions in the studied locations to mitigate the heightened health risks associated with particulate matter pollution. The calculated RR, ER, and AF values offer crucial insights into the complex relationship between PM exposure and adverse health outcomes, providing a foundation for informed decision-making and future research endeavors.

The goal of this paper is to present a low-cost, low-power prototype of a pulsed Ultra Wide Band UWB) oscillator and an UWB elliptical dipole antenna integrated on the same Radio Frequency (RF) Printed Circuit Board (PCB) and its digital control board for Real Time Locating System (RTLS) applications. The design is compatible with IEEE 802.15.4 high rate pulse repetition UWB standard being able to work between 6 GHz and 8.5 GHz with 500 MHz bandwidth and with a pulse duration of 2 ns. The UWB system has been designed using the CST Microwave Studio transient Electro-Magnetic (EM) circuit co-simulation method. This method integrates the functional circuit simulation together with the full wave (EM) simulation of the PCB’s 3D model allowing fast parameter tuning. The PCB has been manufactured and the entire system has been assembled and measured. Simulated and measured results are in excellent agreement with respect to the radiation performances as well as the power consumptions.

Lysine is the first limiting essential amino acid in rice because it is present in the lowest quantity compared to all the other amino acids. Amino acids are the building block of proteins and play an essential role in maintaining the human body’s healthy functioning. Rice is a staple food for large proportion of the global population, thus increasing the lysine content in rice will improve its nutritional value. In this paper, we studied the lysine biosynthesis pathway in rice (Oryza Sativa) to identify the regulators of the lysine reporter gene LYSA (LOC_Os02g24354). Genetically intervening at the regulators has the potential to increase the overall lysine content in rice. We modeled the lysine biosynthesis pathway in rice seedlings under normal and saline (NaCl) stress conditions using Bayesian networks. We estimated the model parameters using experimental data and identified the gene DAPF(LOC_Os12g37960) as a positive regulator of the lysine reporter gene LYSA under both normal and saline stress conditions. Based on this analysis, we conclude that the gene DAPF is a potent candidate for genetic intervention. Upregulating DAPF using methods such as CRISPR-Cas9 has the potential to upregulate the lysine reporter gene LYSA and increase the overall lysine content in rice.

It is widely discussed that growth of GDP has a vague impact on environmental pollution due to the emissions of carbon dioxide from consumed fossil fuels in production, transportation and power generation, and creation of required instruments to control environmental pollution as well. Due to the fact that environmental pollution can be a reason of mortality increase in a society, the main purpose of this study is to investigate the relationship between economic growth, fossil fuel consumption, mortality (from cardiovascular disease, cancer, diabetes and chronic respiratory disease) and environmental pollution using Generalized Method of Moments (GMM) estimation technique in the case of CIS member states over the period of 1993-2018. The major results revealed CO2 emissions in in the region of CIS have a positive effect on increase of mortality from cardiovascular disease, cancer, diabetes and chronic respiratory disease. In regards to fossil fuel consumption, the estimation proved that this variable affects mortality from cardiovascular disease, cancer, diabetes and chronic respiratory disease positively. In addition, we found effect of economic growth, population growth and inflation rate positively, while any improvement in human development index (HDI) has a negative effect on increase of mortality from cardiovascular disease, cancer, diabetes and chronic respiratory disease in the CIS region. It is recommended that the CIS member states carry out different policies to improve energy transition indicating movement from fossil fuel energy sources to renewable ones. Moreover, we recommend the CIS member states to enhance various policies for easy access to the electricity from green sources and increase of renewable supply through improved technologies, sustainable economic growth, and increase of using green source in daily social life.

Corynebacterium glutamicum is a Gram-positive bacterium found in soil where the condition changes demand plasticity of the regulatory interactions, which study at the global scale has been challenged by the lack of data integration. Here, we update the manually-curated C. glutamicum transcriptional regulatory network, now including protein-protein interactions having a direct effect on gene transcription. The network model with regulations supported by any experimental evidence increased by 557 interactions regarding the previous (2018) version. 73 interactions supported by directed experiments were also included in a second model. We included 545 sRNA-mediated regulations in a third model with a total of 5164 interactions. We deposited the three network models in Abasy Atlas v2.4. We study the C. glutamicum regulatory structure by comparing it against the networks for more than 40 species, finding it to contrast in several global structural properties. We analyze the system-level components of the networks, finding that the inclusion of the sRNAs regulations changes their proportions, transferring part of the basal machinery to the modular class and increasing the number of modules while decreasing their size. Finally, we use strong networks of three model organisms to provide insights in future directions of the C. glutamicum network characterization.

Regulatory agencies across the Latin American Region have strengthened the regulatory science through the development of new tools, standards and various other related parameters to evaluate and assess safety, efficacy, quality and performance. The former have been implemented to promote and incorporate new drugs and technologies, which still, are a challenge to well-established regulatory frameworks. Furthermore, in today’s environment, the existing regulatory framework protecting public’s health creates barriers for market entry of novel drugs and medical devices. This article aims to the pioneering work that Cuban Regulatory Agency (CECMED) has been developing with the aim to build a strong regulatory framework geared to accelerated innovation and the successful transition from research and development to clinical development. The Office of Innovation recently established at the CECMED is the first flagship in Latin America and the Caribbean region. Its aim is to play a leading role as a driving force for the national and regional biopharmaceutical innovation. This article will discuss the Office of Innovation its conceptualisation and management taking into account the Latin American regional and national Cuban context.

This paper presents a hybrid modelling approach that combines physics-based electromigration modelling (PEM) and statistical methods to evaluate the electromigration (EM) limits of nano-interconnects in mesh networks. The approach, which is also compatible with standard Place and Route (P&R) tools and practices, takes into account the positive impact of network redundancy on EM current limits. The study shows that conventional methods underestimate the EM current limits of a power delivery network (PDN) unit-cell by 80% due to their lack of consideration for redundancy. Additionally, the time-to-failure (TTF) distributions of a PDN unit-cell adhered to a lognormal distribution, where the lognormal sigma, σlogn, exhibits a 55% reduction compared to that of the single constituent interconnects. The study also found the negative voltage (i.e. ground or Vss) grid to be more susceptible to EM than the positive voltage, i.e. Vdd grid. In the examined grid unit-cell design, both the number of interconnect sites prone to voiding and also the magnitude of the peak tensile stress within the nano-interconnects were found to be 2-folds as high in the Vss case compared to Vdd. lognormal sigma of TFF for the grid unit-cells, σ_(logn-tile), show a marked reduction compared to the lognormal sigma of the constituent single interconnects, σ_logn, with a 50% and 66% decrease compared to single interconnects, for downstream (Vss) and upstream (Vdd), respectively. In addition, σ_(logn-tile) was 3-folds higher for downstream (Vss) compared to upstream (Vdd), whilst, in contrast this difference was only 2-folds at single interconnect level. 4.13-folds higher TTF50% was observed at grid unit-cell level for upstream compared to downstream operation which was also more pronounced than in the single interconnect level where the difference was only 2-folds. This research provides valuable insights into EM aging of nano-interconnects in mesh networks and could pragmatically enhance the accuracy of EM compliance evaluation methods.

A series of novel chiral nonmetallocene pincer-type rare earth metal dialkyl complexes bearing the chiral monoanionic tridentate C2-symmetric 1,3-bis(oxazolinymethylidene)isoindoline (BOXMI) ligand (BOXMI)Ln(CH2SiMe3)2 1-3 (1, Ln = Sc, yield = 57%; 2, Ln = Lu, yield = 55%; 3, Ln = Y, yield = 62%) have been prepared in moderate yields via the acid-base reaction between the BOXMI ligand and rare earth metal tri(trimethylsilylmethyl) complexes. The X-ray diffractions show that both of the complexes 1 and 2 contain one Boxmi ligand and two trimethylsilylmethyl ligands, adopting a distorted-trigonal-bipyramidal configuration. In the presence of cocatalyst such as borate and AlR3, these complexes 1-3 exhibit high activities up to 6.8 × 104 (g of polymer)/(molLn h) and high cis-1,4-selectivities up to 97%) in the polymerization of isoprene in toluene, yielding the cis-1,4-polyisoprenes with high molecular weights (Mn up to 710000 g/mol) and bimodal molecular weight distributions (Mw/Mn = 2.0-4.5).

This pioneering study explores the geospatial and temporal patterns of natural and human-induced disasters from 1900 to 2024, providing essential insights into their global distribution and impacts. Utilizing the comprehensive international EM-DAT database, our analysis reveals significant trends and disparities in disaster occurrences and their widespread consequences. Results showed a dramatic escalation in both natural and man-made (technological) disasters over the decades, with notable surges in the 1991-2000 and 2001-2010 periods. A total of 25,836 disasters were recorded worldwide, of which 69.41% were natural disasters (16,567) and 30.59% were man-made (technological) disasters (9,269). The most significant increase in natural disasters occurred from 1961-1970, while man-made (technological) disasters surged substantially from 1981-1990. Seasonal trends reveal that floods peak in January and July, while storms are most frequent in June and October. Droughts and floods are the most devastating in terms of human lives, while storms and earthquakes cause the highest economic losses. The most substantial economic losses were reported during the 2001-2010 period, driven by catastrophic natural disasters in Asia and North America. Our research highlights Asia as the most disaster-prone continent, accounting for 41.75% of global events, with natural disasters making up 61.89% of these events. Oceania, despite experiencing fewer total disasters, shows a remarkable 91.51% of these as natural disasters. Africa is notable for its high incidence of man-made (technological) disasters, which constitute 43.79% of the continent's disaster events. Europe, representing 11.96% of total disasters, exhibits a balanced distribution but tends towards natural disasters at 64.54%. Examining specific countries, China, India, and the United States emerged as the most frequently affected by both natural and man-made (technological) disasters. The impact of these disasters has been immense, with economic losses reaching their highest during the decade of 2010-2020, largely due to natural disasters. The human toll has been equally significant, with Asia recording the most fatalities and Africa the most injuries. Particularly, the decade from 2001 to 2010 experienced the greatest economic losses, primarily driven by natural disasters in Asia and North America. These insights highlight the urgent need for tailored disaster risk management strategies that address the distinct challenges and impacts in various regions. By understanding historical disaster patterns, policymakers and stakeholders can better anticipate and manage future risks, ultimately safeguarding lives and economies.

Background: Emerging data indicate that radiotherapy can modulate antitumour immune responses. Regulatory T cells (Tregs) are a key immunosuppressive subpopulation of interest. We aimed to evaluate the impact of conventional fractionated radiotherapy on circulating Treg levels in melanoma patients and to determine the correlation between these changes and survival. Understanding radiotherapy–immunity interactions may facilitate personalized combination therapies. Methods: Peripheral blood samples from 32 melanoma patients were analysed to quantify Tregs before and 1-3 months after regional lymph node radiotherapy using flow cytometry. Tregs were characterized as CD4+/CD25+/CD127-. Total CD4+ T cells were also evaluated. Changes were compared to those in a control group of 30 tumor-free patients. Overall survival was correlated with T-cell subset dynamics induced by radiotherapy. Results: At baseline, the median percentage of Tregs was not significantly lower in melanoma patients than in controls (7.4% vs 8.32%, p=0.17). Radiotherapy markedly increased the median Treg count to 10.01% (p=0.0008), with a concomitant increase in total CD4+ cells (to 11.71%, p=0.001), indicating systemic expansion. Patients exhibiting coordinated increases in Treg and CD4+ T cells after treatment had a significantly improved prognosis compared with nonresponders (median OS 27.8 vs 13.1 months, p=0.001). Conclusions: Our study demonstrated the significant effects of standard fractionated radiotherapy on systemic Treg levels in melanoma patients. Radiation-induced changes in T-cell subset proportions hold prognostic value. Monitoring of circulating lymphocyte subsets could facilitate personalized combination therapies.

Purinergic signaling is that nucleotides (especially ATP) and adenosine are utilized as transmitter molecules, which play an important role in the immune system. In the extracellular ventricle, ATP plays a significant role of pro-inflammatory molecules mainly through activating P2 receptors, while adenosine plays the role as anti-inflammatory molecule mainly through activating P1 receptors. As we know，neutrophils are the most abundant immune cells in our circulation and have become an essential part of coordinating a series of complex events during inflammatory diseases. However, due to the destruction of inflammatory substances from neutrophils, the activation of neutrophils is fine-tuned, and purinergic signaling is associated with this process. As a matter of fact, altering the balance between P2 and P1 signals is of great importance for neutrophils to exert immune activities properly. Here, we review the role of purinergic signaling in regulatory function of neutrophils during inflammatory disease, and then discuss the potential contribution of targeted purinergic signals in the treatment of the neutrophil during inflammatory diseases.

An economic and business history approach is used to show the rise and relative failure of the Spanish wind industry during the period between 2004-2015, when Spain became the fourth country after China, the US and Germany in installed capacity of renewable energies and, in relative terms, the second country after Denmark. This study is unique in that it provides an integrated vision of the reasons for the relative fall of Spain in the world ranking of wind energy producers. The methodology of the economic analysis of industrial policies makes it possible to explain the fall in the relative importance of Spain in the international panorama of wind farms. There were no reasons related to technological obsolescence or inability of the CECRE managing renewable energies to explain the fall.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS &gt; 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (&lt; 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS &gt; 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

This literature review investigates how the diverse habitats of Baryonyx walkeri influenced its hunting strategies, with a focus on adaptations for piscivory and generalist predation. The spinosaurid theropod Baryonyx walkeri, known for its distinctive elongated snout and conical teeth, inhabited a variety of environments during the Early Cretaceous period. Fossil evidence suggests that Baryonyx frequented fluvial and lacustrine environments, leading to the hypothesis that its primary diet consisted of fish and other aquatic organisms. Detailed analysis of its cranial morphology reveals a suite of adaptations, including robust forelimbs with a large, sickle-shaped claw, ideal for catching slippery prey. Isotopic analysis of oxygen in Baryonyx indicates a significant reliance on fish and other similar organisms. Comparisons with modern analogs, such as crocodilians, provide further insight into the behavioral ecology of Baryonyx. This review integrates paleontological data with modern ecological analogs to reconstruct the hunting strategies of Baryonyx walkeri. The findings underscore the importance of habitat diversity in shaping the evolutionary pathways of predatory dinosaurs and contribute to a broader understanding of spinosaurid ecology and behavior.

Prostate cancer (PC) is the most frequently diagnosed non-skin cancer in the world. Previous studies showed that genomic alterations represent the most common mechanism for molecular alterations that cause the development and progression of PC. Great efforts have been done to identify common protein-coding genetic variations; however, the impact of non-coding variations including regulatory genetic variants is not still well understood. To gain an understanding of the functional impact of genetic variants, particularly, regulatory variants in PC, we developed an integrative pipeline (AGV) that used whole genome/exome sequences, GWAS SNPs, chromosome conformation capture data, and ChIP-Seq signals to investigate the potential impact of genomic variants on the underlying target genes in PC. We identified 646 putative regulatory variants, of which 30 of them significantly altered the expression of at least one protein-coding gene. Our analysis of chromatin interactions data (Hi-C) revealed that the 30 putative regulatory variants may affect 131 coding and non-coding genes. Interestingly, our study showed the 131 protein-coding genes are involved in disease-related pathways including Reactome and MSigDB in which for most of them targeted treatment options are currently available. Together, our results provide a comprehensive map of genomic variants in PC and revealed their potential contribution to prostate cancer progression and development.

The consequences of manipulations in structure and amino acid composition of native cyclolinopeptide A (CLA) from linen seeds and its linear precursor on their biological activities and mechanisms of action are reviewed. The modifications included truncation of the peptide chain, replacement of amino acid residues with proteinogenic or non-proteinogenic ones, modifications of peptide bond, and others. The studies revealed changes in the immunosuppressive potency of these analogs investigated in a number of in vitro and in vivo experimental models, predominantly in rodents, as well as differences in their postulated mechanism of action. The modified peptides were compared with cyclosporine A and parent CLA. Some of the synthesized and investigated peptides show potential therapeutic usefulness.

Rationale: A wide range of bioactive phytoconstituents from edible fungi, especially therapeutic mushrooms, have the potential to improve health, especially in the case of chronic illnesses. Known for its anti-cancer qualities, ganoderma lucidum has been the focus of multiple clinical studies. Existing systematic reviews imply that more clinical research and methodological refinement are necessary to support its usage as a primary cancer treatment.Objective: The objective of this research is to evaluate the anti-cancer potential of the bioactive phytoconstituents found in mushrooms, specifically Ganoderma lucidum, in a thorough manner. The aim is to conduct a critical assessment of the extant literature, pinpoint any deficiencies, and offer valuable perspectives on the methodological excellence and research requirements in this domain.Method(s): A thorough analysis of published clinical trials was carried out, with a focus on studies that examined the effectiveness of Ganoderma lucidum and other products derived from mushrooms in treating cancer. The study's design, stated results, and methodological rigor were all carefully examined to evaluate the validity and reliability of the conclusions.Results: Despite Ganoderma lucidum's potential against cancer, the evaluation finds insufficient data to support its widespread usage as a primary cancer treatment. Products made from mushrooms, which are frequently sold as dietary supplements, have anti-cancer claims. But since pre-approval is not required under US regulatory framework in order to market food supplements, these statements raise questions regarding their scientific validity.Conclusions/Recommendations: The study's result emphasizes the necessity of more methodological advancement in clinical studies examining Ganoderma lucidum's potential as an anti-cancer agent. It also highlights the significance of thorough scientific validation for goods made from mushrooms that make health claims. To establish accurate claims regarding their anti-cancer effects, recommendations include developing technological methods for the purification of bioactive substances and undertaking thorough studies of mushroom products from different geographical regions. The goal of this thorough analysis is to direct future investigations and support the ethical promotion and use of products derived from mushrooms for medical purposes.

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a "normal" version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no GE product has been approved, as opposed to 22 GT products that cost up to millions of dollars per dose. The FDA has recently added a guideline specific to gene editing that should be understood to enable faster development of GE products; at the same time, the FDA also needs to bring more clarification and make several amendments to this guideline to make it more rational.

Heart is composed of muscle cells called cardiomyocytes, including a specialized population, named pacemaker cells, that form the Cardiac Conduction System (CCS), responsible for generating the action potential dictating heart contractions. Failure of the CCS system leads to cardiac arrhythmias requiring complicated therapies and often surgical implantation of electrical pacemakers. However, recent research focusses on development of novel therapies using biological pacemakers aiming to substitute electrical devices. While most signalling pathways and transcription factors involved in the development of the pacemaker cells are known, the upstream regulatory networks need to be predicted through computer-based databases, mathematical modelling as well as functional testing of the regulatory elements in vivo, indicating the need for further research. Here we summarise the current knowledge about the vertebrate myocardial CCS system and development of the pacemaker cells and emphasise areas of future research to clarify the regulation of muscle pacemaker cells and ease development of biological therapies.

Basic features of seed dormancy are illustrated. The seed overall regulatory network governs seed metabolism and development, and it is coordinated by plant hormones. A functional model focused on abscisic acid (ABA), the foremost plant hormone in dormancy, is used as a framework to critically discuss the literature. Gibberellins (GAs) have a main role in germination, and the ABA – GAs balance is a typical feature of the seed state: ABA dominates during dormancy and GAs prevail through germination. Thus, the literature converges toward envisaging the development switch between dormancy and germination as represented by the ABA/GAs ratio. The ABA – GAs antagonism is based on mutual inhibition, a feature of the regulatory network architecture that characterizes development trajectories based on a regulatory circuit with a bistable switch. Properties of such kind of regulatory architecture are introduced step by step, and it is shown that seed development – towards either dormancy or germination – is more properly represented by a tristable regulatory circuit, whose intermediate metastable states ultimately take one or the other development trajectory. Although the ABA/GAs ratio can conveniently represent the state of the seed overall regulatory network along the seed development trajectory, specific (unknown) dormancy factors are required to determine the development trajectory. The development landscape is shown to provide a well-suited representation of seed states travelling along developmental trajectories, particularly when the states are envisioned as regulatory circuits. Looking at seed dormancy in terms of regulatory circuits and development landscapes offers a valuable perspective to improve our understanding of this biological phenomenon.

The article features the structure and functions of plant synthetic promoters frequently exercised to precisely regulate complex regulatory routes. The composition of plant native promoters together with interacting proteins is presented to provide a better understanding of tasks associated with synthetic promoter development. The production of synthetic promoters is conferred on relatively small libraries produced generally by basic molecular or genetic engineering methods such as cis-element shuffling or domain swapping. Moreover, the preparation of large-scale libraries supported by synthetic DNA fragments, directed evolution, and machine or deep learning methodologies is presented. A particularly interesting group of synthetic promoters are bidirectional forms that enable the putative expression of up to 6–8 genes by one regulatory element. The introduction and controlled expression of several genes after one transgenic event strongly decreases the frequency of such problems as complex segregation patterns and random integration of multiple transgenes. These complications are commonly observed during transgenic crop development through traditional, multistep transformation by genetic constructs containing a single gene. Another path to solving problems associated with the low complexity and homology of already tested DNA fragments is through orthogonal expression systems composed of synthetic promoters and trans-factors that do not occur in nature or arise from different species. Their structure, functions, and applications are rendered in the article.

Alzheimer’s Disease (AD) has no cure. Earlier, we showed that partial inhibition of mitochondrial complex I (MCI) with small molecule CP2 induces adaptive stress response activating multiple neuroprotective mechanisms. Chronic treatment reduced inflammation, improved synaptic and mitochondrial functions, and blocked neurodegeneration in symptomatic APP/PS1 mice, a translational model of AD. Here, using serial block-face scanning electron microscopy (SBFSEM) and three-dimensional (3D) EM reconstructions combined with Western blot analysis and next-generation RNA sequencing, we demonstrate that CP2 treatment also restores mitochondrial morphology and mitochondria-endoplasmic reticulum (ER) communication in the APP/PS1 mouse brain. Using 3D EM volume reconstructions, we show that mitochondria in AD dendrites exist primarily as mitochondria-on-a-string (MOAS). Compared to other morphological phenotypes, MOAS are extensively enveloped in the ER membranes forming multiple mitochondria-ER contact sites (MERCS) known to contribute to abnormal lipid and calcium homeostasis. CP2 treatment specifically reduced MOAS formation, consistent with improved energy homeostasis in the brain, with concomitant reduction in MERCS, ER stress, and improved lipid homeostasis. These data provide novel information on the role MOAS play in AD and additional support for further development of partial MCI inhibitors as disease modifying strategy for AD.

With the fintech industry growing at an unprecedented rate, it is critical to protect cybersecurity and ensure data privacy. The research presented here offers a thorough examination of the challenges faced by financial technology companies, highlighting the growing risks posed by malware, phishing, and network vulnerabilities. As essential components of a proactive defense plan, the report promotes strong cybersecurity measures like frequent security assessments, encryption, and stringent access controls. The findings highlight how important it is for fintech companies to give cybersecurity equal importance with open and honest data privacy policies in order to win over customers. In order to protect the industry from cybersecurity risks regulatory compliance, intrusion detection systems, and collaborative information sharing are considered essential components. The article advises businesses to include cybersecurity and data privacy into their core business operations and customer relations, highlighting the critical role these factors play in sustaining success in the rapidly evolving fintech industry.

The global trend towards increased demand for organic food, greener environments, and the integration of biological control agents into pest management strategies has greatly enhanced the need for biological pesticides (biopesticides). Biopesticides are generally environmentally friendly and are made from micro-organisms or other natural substances. Despite their great potential, relatively few have been registered and commercialised in Nigeria compared to other African countries such as South Africa and Kenya. Biological active agents are so diverse such that ap-plying the same safety standards or environmental conditions to all of them is almost impossible. A review of risk assessment processes and comparative assessments of Nigeria's biopesticide regulations with other developing African countries and developed regions was conducted. Prolonged field testing, lack of bridged risk assessments and technical checklists have been identified as key factors hampering the timely development and commercialisation of biopesti-cides in Nigeria. Recommendations on necessary changes to the existing Nigeria biopesticide regulations have been made. Risk assessment matrices for microbial and biochemical biopesti-cides and a scientific/technical checklist have also been developed. Harmonisation and data ex-change among other countries in the region will also enhance the advancement of scientific and technical knowledge for sustainable regulation and cross-border trade.

The first group to build artificial general intelligence or AGI stands to gain a significant strategic and market advantage over competitors, so companies, universities, militaries, and other actors have strong incentives to race to build AGI first. An AGI race would be dangerous, though, because it would prioritize capabilities over safety and increase the risk of existential catastrophe. A self-regulatory organization (SRO) for AGI may be able to change incentives to favor safety over capabilities and encourage cooperation rather than racing.

In May of 2022, millions of U.S. parents faced uncertainty in safely feeding their infants due to the infant formula shortage. Methods: An anonymous, electronic, cross-sectional, retrospective survey was used. Results: U.S. parents (n =187) whose infants were 10.2 weeks old during the short-age completed the survey. Eighty-one percent of parents switched formulas during the shortage, 87% switched because they could not find the formula they typically used, 34% switched 3-5 times, 29% of parents visited ≥ 4 stores/24 hours and 26% of parents traveled >20 miles/24 hours to purchase formula. Use of infant formula increased (p< 0.01); in infants requiring specialty for-mula, use of intact cow’s milk formula increased (p < 0.05) and use of premature infant formulas decreased (p < 0.05). Infants relying on specialty formulas experienced at least one undesirable outcome compared with non-specialty users. Parents used social media, relatives/friends, and healthcare providers for support during the shortage, but their helpfulness scores were suboptimal. Parents reported needs for greater infant formula availability, free prenatal lactation education and postpartum lactation support. Conclusions: Government, regulatory and healthcare policy oversight are needed to protect the infant feeding system, including more commercially available products, access to banked donor milk and lactation support.