Myelodysplastic syndromes (MDS) are diseases that occur when blood-producing cells in the bone marrow are damaged; such damage can affect one or more types of blood cells. Common types of MDS are refractory anemia with ring sideroblasts and refractory anemia with excess blasts (MDS-RS and MDS-EB, respectively). This work analyzed the proteomics of the medullary plasma of 10 patients with MDS-RS and MDS-EB compared to healthy control people. Overexpressed proteins that may be potential candidates for biological markers for the evaluation, study, and diagnosis of these diseases have been identified. These samples were subjected to immunodepleting, concentrated, and digested for further analysis by mass spectrometry. The ratios between selected groups and healthy people were calculated. Seven overexpressed proteins in both syndromes were identified as potential biomarker candidates: vitronectin (VTN), (2) fibrinogen (FGA), (3) pregnancy zone protein (PZP), (4) kininogen (KNG1), (5) immunoglobulin lambda chain (IGLL1), (6) complement factor C4b, and (7) hemopexin (HPX). A modified affinity chromatographic column with lectin frutalin (FTL) was used for non-depleted samples. Immunoglobulin M (IgM) was expressed in the samples from both syndromes. Surprisingly, IgM from patients with syndromes was over retained on the frutalin (FTL) column when compared with the control group. We further hypothesized that over retention of this protein by the FTL is due to the presence of α-galactosidic residues in the IgM of MDS-RS and MDS-EB patients. Differential recognition of proteins on non-depleted samples from the use of FTL appears to be a powerful tool for proteomic analysis.

Type 2 Diabetes Mellitus and Alzheimer's disease are two diseases with a high incidence today that share similar pathophysiological mechanisms suggesting a potential causal relationship between them. In fact, Alzheimer-associated Mellitus Diabetes is also known as Type 3 Diabetes Mellitus and constitutes a diabetes intricately linked to Alzheimer's disease. Central to this association is insulin resistance, a key factor leading to decreased insulin sensitivity, hyperglycemia, and impaired glucose uptake. Because of this, the brain is altered resulting in energy deficits and neuronal damage associated with neurodegenerative disorder characteristic of Alzheimer's disease. Both diseases exhibit common biochemical and physiological characteristics such as inflammation, mitochondrial dysfunction, oxidative stress, and the formation of advanced glycation end products. Understanding the complex pathophysiology of Type 3 Mellitus Diabetes and identifying common features shared with Diabetes and Alzheimer's disease are essential steps towards potential therapeutic interventions targeting the insulin resistance pathway. The authors of this review on the relationships between type 2 diabetes and Alzheimer's disease have developed two works. In the first (Relationships between Type 2 Diabetes Mellitus and Alzheimer's Disease. I. Common pathogenic mechanisms), authors explore the shared (physiological, genetics and molecular) pathological changes occurring in Type 2 Mellitus Diabetes and Alzheimer's disease as well as pathways such as AMPK, PPARγ, cAMP, and PI3K/Akt as potential targets for managing Type 3 Diabetes Mellitus. By exploring these intricate mechanisms, the goal is to uncover their interdependencies and facilitate the discovery of innovative pharmacological and nutritional (epigenetics) strategies. In the second paper (Relationships between Type 2 Diabetes Mellitus and Alzheimer's Disease. II Potential therapies) we describe possible nutritional intervention, particularly dietary patterns and phytochemicals that can enhance the effects of pharmaceutical drugs designed against pathological mechanisms involved in the complex dual disease Type 2 Diabetes Mellitus and Alzheimer's disease (or in Type 3 Diabetes Mellitus as other authors consider).

The spatial segregation is a characteristic of Latin American cities, resulting in distinct dynamics of social inclusion and exclusion at both spatial and identity levels. Then, specific green spaces may convert into appreciated and contested territories, where various actors negotiate their uses and regulations. Considering a case-study in a green icon of the metropolitan city of Santiago de Chile, the main objective of the present study was to describe and comprehend the uses and meanings of the Quebrada Macul park among different social groups over the past two decades. We employed qualitative methods including six in-depth interviews with key informants (social and ecological leaders, historical neighbors, and park workers), five participant observations in the park, and statistical analysis of visitors. Results reveal that (1) the transition of being a popularly used hill to a metropolitan park rises tensions between public and private statuses of place; (2) conflicts emerge regarding who uses the space and how, reflecting power dynamics among different social groups; (3) the park, beyond being a public space, holds significant identity value for its historical residents, both for those who fought for its recovery and those who have lived closely, so processes of forgetfulness might be resentful. We conclude on enduring meanings of the park associated with the struggle for the place among different groups, highlighting the role of memory for the social integration of groups among natural spaces.

Hepatitis B virus (HBV) remains a dominant cause of hepatocellular carcinoma (HCC). Recently it was shown that HBV and woodchuck hepatitis virus (WHV) integrate into hepatocyte genome minutes after invasion. Retrotransposons and transposable sequences were frequent sites of the initial insertions suggesting a mechanism for spontaneous HBV DNA disperse throughout hepatocyte genome. Several somatic genes were also identified as early insertional targets in infected hepatocytes and woodchuck livers. Head-to-tail joints (HTJs) dominated amongst fusions indicating their creation by non-homologous-end-joining (NHEJ). Their formation coincided with robust oxidative damage of hepatocyte DNA. This was associated with activation of the poly(ADP-ribose) polymerase 1 (PARP1)-mediated dsDNA repair as reflected by augmented transcription of PARP1 and XRCC1, the PARP1 binding partner, OGG1, a responder to oxidative DNA damage, and by increased activity of NAD+, a marker of PARP1 activation, and HO1, an indicator of cell oxidative stress. The engagement of the PARP1-mediated NHEJ repair pathway explains HTJ format of the initial merges. The findings showed that HBV and WHV are immediate inducers of oxidative DNA damage, hijack dsDNA repair to integrate into hepatocyte genome and by this may initiate pro-oncogenic process. Tracking initial integrations may uncover early markers of HCC and help to explain HBV-associated oncogenesis.

A partial extraction procedure was used to study the distribution of uranium in the mineral phases of rocks of an aquifer of sandy-clay deposits of the Vendian in the northwest of Russia. This work is a part of a research project to develop a method for combined radiocarbon and uranium-isotope dating of groundwater. Representative aliquots of each core sample were subjected to five "partial" extractions by treatment with: distilled water, low mineralized fresh natural groundwater, minopolycarboxylic acid chelating agent (0.05M EDTA), 0.5M HCl, 15M HNO₃, and a total digestion, with U isotopes reported in this study for each procedure. The following mineral phases of core samples: adsorbed material, carbonate minerals, amorphous iron oxides, aluminosilicates partial digestion and a crystalline iron oxides, aluminosilicates total digestion and a clay/quartz resistate were characterized. Red-colored siltstones depleted in uranium in relatively readily soluble mineral phases. The concentration of adsorbed uranium was established in the amount of 15.8±2.1 - 30.5±3.9 μg/kg. Carbonate minerals contain even less of this element. In iron hydroxides and the most readily soluble aluminosilicates, its concentrations are in the range 168±24 - 212±28 μg/kg. The most insoluble fraction contains 1.65±0.21 - 4.32±0.45 mg/kg of uranium. In green-colored siltstones, the concentration of adsorbed uranium is much higher: 106±14 - 364±43 μg/kg. Carbonate minerals and amorphous iron oxides contain 1.91±0.21 - 2.34±0.26 mg/kg of uranium. In aluminosilicates and a clay/quartz resistate, uranium concentrations are 5.6±0.5 - 16.8±1.4 mg/kg. Elevated values of ²³⁴U:²³⁸U activity ratio prevail in the adsorbed material and iron hydroxides. In aluminosilicates and clay/quartz resistate, the values decrease. This indicates the replacement of primary sedimentogenic uranium by secondary hydrogenic uranium adsorbed on the surface of minerals and coprecipitated with iron hydroxides. The results obtained made it possible to carry out preliminary quantitative estimates of the retardation factor and recoil loss factor of uranium in the groundwater of siltstones of the studied Vendian aquifer.

The construction industry has a notable negative impact on the environment; thus, the promotion of the use of timber structures is an alternative to mitigate its effects. The research develops an artificial intelligence-based decision approach in the calculation of timber structures focused on the enhancement of the sustainability of roof structures. Based on the optimization carried out through genetic algorithms and the framework established in Eurocode 5, a general set of equations has been proposed for a laminated timber roof structure. The tool, which determines the most suitable roof structure for each strength class of laminated timber, allows for the determination of the dimensions of beams and purlins and their respective separations in order to minimize wood consumption. The ultimate goal is to offer multiple solutions regarding strength classes and structural designs in order to foster informed sustainable choices that promote efficient use of resources in construction.

Several review articles about megachurch studies have been published recently concentrating their work on USA, Europe, and other parts of the world, with just a few references about Latin American megachurches. For that reason, this article aims to identify some of the characteristics of Latin American Evangelical megachurches by looking at relevant literature, especially that produced in the region, in Spanish and Portuguese, which is usually overlooked by researchers in Global North. Since this research field is still limited in Latin America, areas, where further work is necessary, are identified. Three general catalysts for the emergence of megachurches in the region, church growth methodologies, Pentecostalization, and theologies of growth, serve as guides to organize the review process. The discussion shows several potential areas of research in a variety of fields such as theology, ecclesiology, organizational theory, leadership, gender studies, and ethics, are proposed from the review.

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5'end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5’ terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I or MDA5 receptors, a way to overcome antiviral innate immune response. Overall, natural 5′ terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host-cell interactions driving the development of acute or persistent EV-B infections.

Complex-structured polymeric microparticles hold significant promise as advance in next-generation medicine mostly due to demand from developing targeted drug delivery. However, the conventional methods for producing these microparticles of defined size, shape and sophisticated composition often face challenges in scalability, reliance on specialized components such as micro-patterned templates, or have limited control over particle size distribution and cargo release kinetics. In this study, we introduce a novel and reliably scalable approach for manufacturing microparticles of defined structures and sizes with variable parameters. The concept behind this method involves the deposition of a specific number of polymer layers on a substrate with low surface energy. Each layer can serve as either the carrier for cargo or a programmable shell-former with predefined permeability. Subsequently, this layered structure is precisely cut into desired-sized blanks using a laser. The manufacturing process is completed by applying of heat to the substrate what results on sealing the edges of the blanks. The combination of the high surface tension of the molten polymer and the low surface energy of the substrate enables the formation of discrete particles, each possessing semi-spherical or other designed geometries determined by their internal composition. Such anisotropic microparticles are envisaged versatile applications.

Aim: The main purpose of this feasibility study was to estimate compliance and acceptability rate of a 9-Steps mobile app preparation program. Subsequently, to assess its impact regarding attitudes towards smoking cessation. Methods: The program was only available on versions above iOS 13.3. The ecological study collected user’s data via the app from 04/07/2021 to 28/07/2021. Results: A total of 2331 ecological users completed onboarding; 1926 users (73.9%) completed the step 0 and only 265 users continued in step 1. On average, participants actively engaged with intra-steps activities (85,1%). Most users were highly satisfied at the end of each step. On average 86% found the content of each step comprehensive and relevant. Mann-Whitney tests demonstrated positive changes in attitudes toward smoking cessation on the less confident users: willing (3 to 5, p <.05); confidence (3 to 5, p <.001) and readiness to quit (3 to 5, p <.001). Conclusions: This ecological study corroborates the expected dropout between first use and regular use of health mobile apps. However, engagement and satisfaction rates support the feasibility and acceptability of a 9-step preparation program. Additional research is needed to better understand determinants of regular use of mobile apps and its impact on the target behavior.

We present large eddy simulations of a mid-latitude open ocean front using a modified state of the art computational fluid dynamics code. We investigate the energy and information fluxes at the submesoscale/small-scale range in the absence of any atmospheric forcing. We find submesoscale conditions (Ro∼1, Ri∼1) near surface, within baroclinic structures related with partially imbalanced frontogenetic activity. Near surface, the simulations show a significant scale coupling on scales larger than ∼103(m). This is manifested as a strong direct energy cascade and intense mutual communication between scales, where the latter was evaluated using an estimator based on Mutual Information Theory. At scales smaller than ∼103(m) the results show near-zero energy flux, however, at this scale range, the estimator of mutual communication still shows values corresponding with a significant level of communication between them. This fact motivates to investigate the nature of the self-organized turbulent motion at this scale range with weak energetic coupling but where communication between scales is still significant and to inquire into the existence of synchronization or functional relationships between scales with emphasis on eventual underlying non-local processes.

Taiwan's bed and breakfast (B&B) development has been more than 25 years ago, from the first generation of retirement to the B&B industry, serving tourists from all over the world accom-modation, providing breakfast and accommodation mode to the present, after the change of employees from the second generation, more and more attention is paid to the cultivation and cultivation of business ability. With the advent of the era of AI technology networking, the ca-pabilities required for B&B operation are more focused on all aspects of service, and the good marketing ability of B&B can promote a green chimney-free tourism economy, which is also a favorite industry of various governments and the public. This study explores the basic vocational competency indicators required for running a B&B, with (1)EQ emotion management skills, (2)Financial management ability, (3)(SK) technical skills, and (4)Marketing and promotion management capabilities. Through the study method, the K-S Z test was determined by the con-sensus conclusion of expert reliability and validity p value

A significant percentage of children suffer from neurodevelopmental aberrations, which have long-term effects on both individuals and society. Since the developmental timelines of different brain regions vary, the type, severity and timing of harmful exposures are crucial for understanding the specific pathological processes and consequences involved. During development, the cerebellum is one of the first brain structures to begin to differentiate, but one of the last to achieve maturity. This relatively long period underscores its vulnerability to detrimental environmental exposures throughout gestation. Moreover, as the postnatal functionality of the cerebellum is multifaceted, enveloping sensorimotor, cognitive, and emotional domains, prenatal disruptions in cerebellar development can result in a variety of neurological and mental health disorders. Here, we review major intrauterine insults that affect cerebellar development in both humans and rodents, ranging from abuse of toxic chemical agents such as alcohol and nicotine, to stress and sleep, malnutrition as well as infections. Understanding these pathological mechanisms in the context of the different stages of cerebellar development in humans and rodents may help us to identify critical and vulnerable periods and thereby to prevent the risk of associated prenatal and early postnatal damage that can lead to lifelong neurological and cognitive disabilities.

For the World Health Organization, and specifically for the International Coordination Committee, the need to bring forward discussions on non-clinical trials in human models, such as vaccine trials in pregnant women, with the aim of demonstrating immunity in newborns, has been addressed. This literature review seeks to investigate the relationship between mothers and newborns in terms of the transfer of IgG antibodies against SARS-CoV-2. Most of the literary evidence shows that the substantial transfer of transplacental and lactational antibodies to infants confers protection even when the baby is exposed to the disease. However, accurate and conclusive evidence on the safety and efficacy of COVID-19 vaccines during pregnancy will be a key factor in facilitating the decision-making process for pregnant women to ensure the safety of mother and baby.

Compound databases of natural products have a major impact on drug discovery projects and other areas of research. The number of databases in the public domain with compounds from natural origin is increasing. Several countries have initiatives in place to construct and maintain compound databases that are representative of their diversity. Examples are Brazil, France, Panama and recently Vietnam. Herein, we discuss the first version of BIOFACQUIM, a novel compound database with natural products isolated and characterized in Mexico. We discuss its construction, curation, and a complete chemoinformatic characterization of the content and coverage in chemical space. It is reported the profile of physicochemical properties, scaffold content, and diversity, as well as structural diversity based on molecular fingerprints. BIOFACQUIM is freely available.

Meprin α and β are zinc-dependent proteinases implicated in multiple diseases including cancers, fibrosis, and Alzheimer’s. However, until recently, only a few inhibitors of either meprin were reported and no inhibitors are in pre-clinical development. Moreover, inhibitors of other metzincins developed in previous years are not effective in inhibiting meprins suggesting the need for de novo discovery effort. To address the paucity of tractable meprin inhibitors we developed ultra-high throughput assays and conducted parallel screening of >650,000 compounds against each meprin. As a result of this effort, we identified 5 selective meprin α hits belonging to three different chemotypes (triazole-hydroxyacetamides, sulfonamide-hydroxypropanamides, and phenoxy-hydroxyacetamides). These hits demonstrated a nanomolar to micromolar inhibitory activity against meprin α with low cytotoxicity and >30-fold selectivity against meprin β and other related metzincincs. These are the most selective inhibitors of meprin α to date.

There is a growing interest in glial cells in the central nervous system due to their important role in maintaining brain homeostasis both under physiological conditions and after injury. A significant amount of evidence has been accumulated regarding their capacity to exert either pro-inflammatory or anti-inflammatory effects under different pathological conditions. In combination with their known proliferative potential, they contribute not only to the limitation of brain damage and tissue remodeling but also to neuronal repair and synaptic recovery. Moreover, reactive glial cells can modulate the processes of neurogenesis, proliferation, and migration of neurons in the existing neural circuits in the adult brain. By discovering precise signals within specific niches, the regulation of sequential processes in adult neurogenesis holds the potential to unlock strategies that can stimulate the generation of functional neurons, whether in response to injury or as a means of addressing degenerative neurological conditions. Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation of the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving post-stroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury.

HepG2 cells reconstituted with Hepatitis B virus (HBV) entry receptor sodium taurocholate co-transporting polypeptide (NTCP) are widely used as a convenient in vitro cell culture infection model for HBV replication studies. As such, it is pertinent that HBV infectivity is maintained at steady-state levels for accurate interpretation of in vitro data. However, variations in HBV infection efficiency due to imbalanced NTCP expression levels in the HepG2 cell line may affect experimental results. In this study, we performed single cell cloning of HepG2-NTCP-A3 parental cells via limiting dilution and obtained multiple subclones with increased permissiveness to HBV. Specifically, one subclone (HepG2-NTCP-A3/C2) yielded more than 4-fold higher HBV infection compared to the HepG2-NTCP-A3 parental clone. In addition, though HBV infectivity was universally reduced in the absence of polyethylene glycol (PEG), subclone C2 maintained relatively greater permissiveness under PEG-free conditions, suggesting the functional heterogeneity within parental HepG2-NTCP-A3 may be exploitable in developing a PEG-free HBV infection model. The increased viral production correlated with increased intracellular viral antigen expression as evidenced through HBcAg immunofluorescence staining. Further, these subclones were found to express different levels of NTCP, albeit with no remarkable morphology or cell growth differences. In conclusion, we isolated subclones of HepG2-NTCP-A3 which support efficient HBV production and thus provide an improved in vitro HBV infection model.

ND1 subunit possesses the majority of the inhibitor binding domain of the human MRC-I. This is an attractive target for the search for new inhibitors that seek mitochondrial dysfunction. It is known, from in vitro experiments, some metabolites from Annona muricata called acetogenins have important biological activities such as anticancer, antiparasitic, and insecticide. Previous studies propose an inhibitory activity of bovine MRC-I by bis-THF acetogenins such as annocatacin B, however, there are few studies on its inhibitory effect on human MRC-I. In this work, we evaluate the molecular and energetic affinity of the annocatacin B molecule with the human ND1 subunit in order to elucidate its potential capacity to be a good inhibitor of this subunit. For this purpose, QM optimizations, MD simulations and MM/PBSA analysis were performed. As a control to compare our outcomes, the molecule rotenone, which is a known MRC-I inhibitor, was chosen. Our results show that annocatacin B has a greater affinity for the ND1 structure, its size and folding were probably the main characteristics that contributed to stabilize the molecular complex. Furthermore, the MM/PBSA calculations showed a 35% stronger BFE compared to the rotenone complex. Detailed analysis of the BFE shows that the aliphatic chains of annocatacin B play a key role in molecular coupling by distributing favorable interactions throughout the major part of the ND1 structure. These results are consistent with experimental studies that mention that acetogenins may be good inhibitors of MRC-I.

Interaction of an electromagnetic field with matter in a laser cavity without the assumption of a fixed direction of the transverse electric field, described by the two-level Maxwell-Bloch equations, is studied. By using a perturbative nonlinear analysis, performed near the laser threshold, we report on the derivation of the laser (3+1)D vectorial complex cubic-quintic complex Ginzburg-Landau equation. Furthermore, we study the modulational instability of the plane waves both theoretically using the linear stability analysis, and numerically, using direct simulations via the split-step Fourier method. The linear theory predicts instability for any amplitude of the primary waves. Our numerical simulations confirm the theoretical predictions of the linear theory as well as the threshold of the amplitude of perturbations. The system understudy shows a deep dependence on the laser cavity parameters, for which there appear wave patterns in accordance with the predictions from the gain spectrum.

The implementation of gold-hydrogel core-shell nanomaterials in novel light-driven technologies requires the development of well-controlled and scalable synthesis protocols with precisely tunable properties. Herein, new insights are presented concerning the importance of using the concentration of gold cores as a control parameter in the seeded precipitation polymerization process to modulate – regardless of core size – relevant fabrication parameters such as encapsulation yield, particle size and shrinkage capacity. Controlling the number of nucleation points results in the facile tuning of the encapsulation process, with yields reaching 99% of gold cores even when using different core sizes at a given particle concentration. This demonstration is extended to the encapsulation of bimodal gold core mixtures with equally precise control on the encapsulation yield, suggesting that this principle could be extended to encapsulating cores composed of other materials. These findings could have significant impact on the development of stimuli-responsive smart materials.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, showing reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

According to global data, there is a male reproductive potential decrease. Pathogenesis of male infertility often is associated with autoimmunity towards sperm antigens essential for fertilization. Antisperm autoantibodies (ASAs) have immobilizing and cytotoxic properties, impairing spermatogenesis, causing sperm agglutination, altering spermatozoa motility and acrosomal reaction, thus preventing ovum fertilization. Infertility diagnosis requires mandatory check for the ASAs. The concept of blood-testis barrier currently is re-formulated with emphasis of informational paracrine and juxtacrine effects, rather than simple anatomical separation. Aetiology of male infertility includes both autoimmune and non-autoimmune diseases, but equally develops through autoimmune links of pathogenesis. Varicocele commonly leads to infertility due to testicular ischemic damage, venous stasis, local hyperthermia, and hypoandrogenism. However, varicocelectomy can alter blood-testis barrier facilitating ASAs production as well. There are contradictory data on the role of ASAs in pathogenesis of varicocele-related infertility. Infection and inflammation both promote ASAs production due to “danger concept” mechanisms and because of antigen mimicry. Systemic pro-autoimmune influences like hyperprolactinemia, hypoandrogenism and hypothyroidism also facilitate ASAs production. Diagnostic value of various ASAs was not yet clearly attributed, and their cut-levels not agreed neither in sera nor in ejaculate. The assessment of the autoimmunity role in pathogenesis of male infertility is ambiguous.

2-(5,6-diphenyl-1,2,4-triazin-3-yl)pyridinium dichloroiodate (I) (1) was synthesized by reacting 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine with ICl in dichloromethane solution. The structural characterization of 1 by SC-XRD analysis was accompanied by elemental analysis, FT-IR, and FT-Raman spectroscopy measurements.

Anticipating and planning for the urgent response to large-scale disasters is critical to increase the probability of survival in these events. These incidents present various challenges that complicate the response, such as unfavorable weather conditions, difficulties in accessing affected areas, and the geographical spread of the victims. Furthermore, local socioeconomic factors such as insufficient prevention education, limited disaster assets, and inadequate coordination between public and private emergency services may complicate these situations. In large-scale emergencies, multiple hotspots are usually observed, which requires efforts to coordinate the strategic allocation of human and material resources in different geographical areas. Therefore, the precise management of these resources based on the specific needs of each area becomes fundamental. To address these complexities, this paper proposes a methodology that models these scenarios as an optimization problem, focusing on the location and allocation of resources in mass casualty incidents. The proposed case study is Mexico City in a post-earthquake scenario, using voluntary geographic information, open government data, and historical data from the September 19, 2017 earthquake. Additionally, it is assumed that the resources that require optimal location and allocation are ambulances, which focus on medical issues that affect the survival of victims. The designed solution involves the use of a metaheuristic optimization technique, along with a parameter tuning technique, to find configurations that perform at different instances of the problem, i.e., different hypothetical scenarios that can be used as a reference for future possible situations. Finally, the objective is to present the different solutions graphically, accompanied by relevant information to facilitate the decision-making process of the authorities responsible for the practical implementation of these solutions.

Ovarian cancer is among the most common causes of female mortality. Despite improvements in diagnostic methods, non-specific symptoms and delayed gynecological exams can lead to late-stage ovarian tumor discovery. In this study, the effect of an anti-cancer compound, 3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide (Compound 1) was examined. Cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, both on cancer stem cells (CSCs), marked as CD49f+ and non-CSCs (CD49f-) were explored. Treatment with Compound 1 reduced the percentage of CSCs compared to non-treated cells (P &lt; 0.001). The expression of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. Both cell lines showed a change in the glycophenotype of the cells, either up or down of its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment of Compound 1 resulted in a statistically significant increase in both early and late apoptosis (P&lt;0.001) suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The metabolic analysis revealed that the treated cancer cells showed reduced metabolic activity compared to the control group (P &lt; 0.001)

The process of oxygenic photosynthesis is primarily driven by two multiprotein complexes known as photosystem II (PSII) and photosystem I (PSI). PSII facilitates the light–induced reactions of water–splitting and plastoquinone reduction, while PSI functions as the light–driven plastocyanin-ferredoxin oxidoreductase. In contrast to the highly conserved structure of PSII among all oxygen–evolving photosynthetic organisms, the structures of PSI exhibit remarkable variations, especially for photosynthetic organisms that grow in special environments. In this review, we make a concise overview of the recent investigations of PSI from photosynthetic microorganisms including prokaryotic cyanobacteria and eukaryotic algae from the perspective of structural biology. All known PSI complexes contain a highly conserved heterodimeric core; however, their pigment compositions and peripheral light-harvesting proteins are substantially flexible. This structural plasticity of PSI reveals the dynamic adaptation to environmental changes for photosynthetic organisms.

The present study was aimed at revealing the influence of the mechanical stress induced by water molecules adsorption on the composition of crystalline phases in the ZrO2–3mol%Y2O3-nanoparticles. Three basic methods have been used to determine the phase transition: neutron diffraction, Raman microspectroscopic scanning, and X-ray diffraction. The fact of phase-structural β → α transformation and the simultaneous presence of two polymorphic structural modifications (β is the phase of the tetragonal syngony and α of monoclinic syngony in nanosized particles (9nm)) under normal physical conditions was established by these methods. Satisfactory consistency was achieved between the results obtained using different techniques.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Sachet water (SW) is a major source of drinking water in most Nigerian homes, thus making it a possible conveyance medium for health risks due to contamination rather than for replenishment of the body. This study collected SW from three busy neighborhoods and investigated for the presence of indicator bacteria – Escherichia coli (E. coli), Total Coliform (TC), Total Heterophilic Bacteria (THB), and Staphylococcus – and some physio-chemical parameters – total dissolved solids (TDS), pH, electrical conductivity (EC), and salinity. Multi-variable and exploratory statistical methods were applied to the results to determine correlations between bacterial contamination levels and perceived brand reputation. Bacteriological test with raw SW samples appeared too numerous to count (TNC) and thus required serial dilutions. After seven dilutions, results obtained revealed that SW brands with good reputation had no TC and E. coli and was statistically significant with groupings of other SW brands (χ2 = 12.28; p < 0.05 and χ2 = 37.96; p < 0.05) respectively. Additionally, SW brands with poor reputation had mean values of TC (19.7X10^8 cfu/ml;14X10^8 cfu/ml1.15X10^8 cfu/ml) and E.coli (18.2X10^8 cfu/ml;38.7X10^8 cfu/ml,32.4X10^8 cfu/ml) exceeding threshold value of zero set by the World Health Organization (WHO). Only one sample from poor reputation brand tested positive for Staphylococcus and was not statistically significant (χ2 =5.2191; p = 0.074). Principal Component Analysis (PCA)/ Factor Analysis (FA) revealed that most of the SW had fecal contamination in an alarming magnitude. Therefore, this study suggests that periodic cleaning of distribution lines, location specific treatment, QC and QA measures should be taken to reduce water security risk for SW consumption in the region.

To achieve n-type doping in diamond, extensive investigations employing first principles have been conducted on various models of phosphorus doping and boron-phosphorus co-doping. The primary focus of this study is to comprehensively analyze the formation energy, band structure, density of states, and ionization energy of these structures. It is observed that within a diamond structure solely composed of phosphorus atoms, the formation energy of an individual carbon atom is excessively high. However, the substitution of two carbon atoms leads to the conversion of diamond into a p-type semiconductor. Upon examining the P-B co-doping structure, it is revealed that the doped impurities exhibit a tendency to form more stable cluster configurations. As the separation between the freely doped atoms and the cluster impurity structure increases, the overall stability of the structure diminishes, consequently resulting in an elevation of the ionization energy. Analysis of the electronic density of states demonstrates that the electron orbit of the B atom makes negligible contributions to the impurity levels during P-B doping.

Atopic dermatitis (AD) is a chronic inflammatory condition which significantly affects quality of life in both patients and their caregivers. Calcineurin inhibitors (CNI) are a class of immunosuppressive drugs predominantly inhibiting T cell mediated immune processes. CNI form complex by binding with immunophilins and in turn inhibit calcineurin and suppress downstream inflammatory pathway. Tacrolimus and pimecrolimus are topical CNI approved for the treatment of mild to severe AD in both children and adults. Application site reactions are frequently seen. They have been issued with black box warning towards increased risk of malignancies but supportive evidence is lacking. Cyclosporine, though highly effective, is used off-label for AD management. It is used for controlling acute flares of AD due to its very rapid onset of action. Nephrotoxicity and hypertension are its serious complications. CNI have not been reported with teratogenicity and may be used conditionally during pregnancy and lactation.

In this present work, we are reporting a novel route for the synthesis of the tetracyclic ring systems, which is a common core of crinipellin via oxidative dearomatization, cycloaddition and oxa- di-pi-methane rearrangement. We considered to exploring a route to tetracyclic core (1e) of Crinipellin and tricyclic core (1g) of Allicaol B through intermolecular diels alder reaction and photochemically 1,2 acyl shift. Moreover, docking study of compound 13 and 16has been investigated against AcrB multidrug efflux pump of Escherichia coli (PDB ID: 1T9U), main protease of SARS COV-2 (PDB ID: 6W63), DNA gyrase of Streptococcus pneumonia (PDB ID: 4Z2C), human estrogen receptor alpha (PDB ID: 3ERT), human lanosterol 14-alpha-demethylase (CYP51)(PDB ID: 3JUS) and cyclooxygenase-2 (Prostaglandin Synthase-2) (PDB ID: 1CX2). The obtained results herein are important for the exploitation of the therapeutic potential of these derivatives as antimicrobial, antiviral, anticancer, antifungal or anti-inflammatory agents.

Signaling modules that integrate the diverse extra- and intracellular inputs to control cell proliferation are essential during both development and adult stages to guarantee organism homeostasis. Mobs are small adaptor proteins that participate in several of these signalling pathways. Here we review recent advances unraveling Mob4 cellular functions, a highly conserved non-catalytic protein, that plays a diversity of roles in cell proliferation, sperm cell differentiation and simultaneously is involved in synapse formation and neural development. In addition, the gene is often overexpressed in a wide range of tumors and is linked to poor clinical outcomes. Nevertheless, Mob4 molecular functions remain poorly defined, although it integrates the core structure of STRIPAK, a kinase/phosphatase protein complex, that can act upstream of the Hippo pathway. In this review we focus on the recent findings of Mob4 functions, that have begun to clarify its critical role on cell proliferation and development of tissues and individuals.

Wood is poised to become a material of choice for future construction. When appropriately managed, it is a renewable material with unique mechanical properties. Beyond its inherent sustainability, the use of wood has a crucial role in addressing climate change concerns due a significantly lower energy consumption and emissions during manufacturing and transportation, while simultaneously acting as a carbon sink. Thus, there has been a growing demand for hardwoods for structural applications, including Castanea sativa Mill., the focal point of this investigation. Albeit in a limited capacity, Eurocode 5-2 offers friction coefficients for softwoods, but it falls short for hardwoods which it is a gap to bridge with this research. These coefficients play a critical role in numerical simulations involving friction, enabling the optimization of joints and, by extension, the overall structural integrity. Test samples were evaluated at 18% moisture content, which is typical of Service Class 2, for various orientations of timber-to-timber and timber-to-steel friction. Considering previous friction coefficients at 12% moisture content, the linear variation was evaluated at an intermediate value of 15%. The results provide an experimental database for numerical simulations and highlight the influence of moisture content on the coefficients, which increase linearly along moisture percentages.

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

Design process can be divided into stages of analysis and synthesis. This paper presents the application of the object-oriented technique to the analysis as well as theoretical considerations concerning to design of gear size ranges. This analysis consists in decomposition of the designed artefact (a gear) according to the rule “from general to details view”. The basics of the object-oriented analysis were formulated. Furthermore, design phases and the objects related to theses phases were discussed. The following models have been considered: hierarchical model, entity-relationship model, data-flow model and object model. Analysis is additionally connected with interactions between particular design phases.

A closed chain of oscillators can be considered as a model of ring-shaped ecosystems, such as atolls or coastal zones of inland reservoirs. As an oscillator model, we use the logistic map that often referred to as an archetypical example of how complex dynamics can arise from very simple nonlinear equations. We investigate the influence of the model parameters both on the nature of oscillations in the oscillator ring and on the spatial structures that arise in this case. Namely, we demonstrate a variety of emerging spatial structures depending on the initial conditions.

The contribution of academics and researchers to the discussion around sustainable rural development planning and its impact on rural communities has grown exponentially in recent years. Understanding trends in sustainable rural development research requires considering the different factors involved and affecting people from a holistic approach. This review examines, through bibliometric studies, the scientific knowledge generated on sustainable rural development planning in the last 50 years, analyzing 6,895 articles published in journals between 1970 and 2020. The results reveal the existence of three clusters and an important growth is observed to respond to the continuous needs in relation to sustainable rural development. This research shows the evolution of a new approach for the planning of sustainable rural development projects in postmodernity: Working with People (WWP). This WWP model, as a conceptual framework from social learning has been validated as a novel proposal in numerous contexts. The bibliometric analysis shows an evolution "From Putting the Last first" to "Working with People in Rural Development" research and the contributions of influential teachers such as Chambers and Cernea. These bibliometric analyses demonstrate the correct approach of WWP model, and open new fields of research in the planning of sustainable rural development projects.

Groove pancreatitis represents a chronic focal form of pancreatitis affecting the zone between the pancreatic head and the duodenal „C” loop, known as the groove area. This is a rare condition that affects the pancreatic periampullary part, including the duodenum and the common bile duct, associated usually with long-term alcohol and tobacco misuse and being more frequent in men than in women. The most common clinical symptoms of groove pancreatitis include weight loss, acute abdominal pain, nausea, and jaundice. This report is about a 66 year old woman with a history of heavy smoking, presenting with weight loss, nausea, and upper abdominal pain. Contrast enhanced computed tomography revealed the existence of a chronic pancreatitis as well as the dilatation of the main pancreatic duct, a cyst of the pancreatic head and enlargement of the biliary tract. Conservatory treatment was initiated but with no improvement of symptoms. Since there was no indication for endoscopic retrograde cholangiopancreatography, we decided to perform a pancreatoduodenectomy, as surgery appears to be the single effective treatment.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of &lt;1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

Engineers make things, make things work, and make things work better and easier. This kind of knowledge is crucial for innovation, and much of the explicit knowledge developed by engineers is embodied in scientific publications. In this paper, we analyze the evolution of publications and citations in Engineering in a middle-income country such as Mexico. Using a database of all Mexican publications in Web of Science from 2004 to 2017, we explore the characteristics of publications that tend to have the greatest impact; this is the highest number of citations. Among the variables studied are the type of collaboration (no collaboration, domestic, bilateral, or multilateral), the number of coauthors and countries, the language of the article, controlling for a coauthor from the USA and the affiliation institution of the Mexican author(s). Our results emphasize the overall importance of joint international efforts and suggest that publications with the highest number of citations are those with multinational collaboration (coauthors from three or more countries), written in English, and when one of the coauthors is from the USA.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Background: Endovascular treatment of popliteal aneurysms (PA) has increased in the last few years, quickly becoming the main treatment in many vascular centers, based on the acceptable and promising outcomes reported in the literature. However, endograft infections are the most dangerous complication as a serious local compromise and usually require open surgical conversion and device explantation to preserve the affected extremity. Case report: We reported two patients admitted to the emergency room for pain and edema in the lower leg. Both patients have undergone exclusion of ruptured PA a few years before by endovascular graft. CTA showed a significant volume of fluid-corpuscular collection related to perianeurysmal abscess collection in both cases. Blood cultures and drained material cultures were positive for Staphylococcus Capitis in the first case and S. Aureus in the second. The antibiotics prophylaxis was performed for 10 days, then, patients underwent an open surgical conversion with a complete explantation of endovascular material and a femoro-popliteal bypass using an autologous vein in the first case and biological bovine pericardium prosthesis in the other case. Furthermore, we have questioned the literature and found eight more cases described in case report article referred to popliteal graft infections by different microorganisms, mostly presenting acute limb ischemia as the first symptom and suggesting endograft explantation with open conversion and autologous vein bypass as the commonest therapeutic choice. Conclusions: Open surgical conversion of popliteal endograft infection is the best strategy to manage peripheral infection of the popliteal stent.

This experimental research presents an easier model for fitting experimental results that can be simulate the dynamical behaviour of a single degree freedom system, SDFS, subjected in a forced vibration in a shaking table. The fractional damping using a Kelvin-Voigt fractional derivative rheological model, KVFRdm, to represent a fractional oscillator and compare with the experimental model.

Abstract: This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses still reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950–1969 and 1970-1794 as well as cancer incidence rates for the period 1998–2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, and diabetes and obesity prevalence near the 2016–2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin’s lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in overweight and obesity, which lowers 25-hydroxyvitamin D concentrations and generates systemic inflammation, a risk factor for cancer. The dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore cancer, would be one based mostly on whole-plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce risk of cancer.Keywords: alcohol consumption; cancer incidence;

SARS-CoV-2, influenza A/B virus (IAV/IBV) and respiratory syncytial virus (RSV) are among the common viruses causing acute respiratory infections. Clinical diagnosis to differentiate these viruses is challenging due to similar clinical presentations, thus laboratory-based real-time RT PCR is the gold standard for diagnosis. The study aimed to evaluate the diagnostic performance of STANDARD M10 Flu/RSV/SARS-CoV-2 (SD Biosensor Inc, Seoul, Korea). This retrospective study was conducted with archived respiratory samples positive and negative for SARS-CoV-2, IAV, IBV or RSV. The evaluation study involved a total of 322 respiratory samples comprising 215 positive samples (49 SARS-CoV-2, 48 IAV, 53 IBV, 65 RSV) and 107 negative samples. All samples were tested with both STANDARD M10 and either Xpert Xpress SARS-CoV-2 or Xpert Xpress Flu/RSV (Cepheid, USA). The sensitivity, specificity, positive predictive value and negative predictive value rates of STANDARD M10 were very similar to Xpert Xpress SARS-CoV-2 or Xpert Xpress Flu/RSV ranges for each virus (98-100%). The overall agreement was 99.4% with 99.1% agreement for positive samples and 100% agreement for negative samples. In conclusion, the STANDARD M10 point-of-care test is suitable for rapid simultaneous detection of SARS-CoV-2, IAV, IBV and RSV.

This research aims to apply Artificial Intelligence (AI) methods, specifically Artificial Immune Systems (AIS), to design an optimal control strategy for a multivariable control plant. Two specific industrial control approaches are investigated: I-PD (Integral-Proportional Derivative) and PI-D (Proportional-Integral Derivative) control. The motivation for using these variations of PID controllers is that they are functionally implemented in modern industrial controllers, where they provide precise process control. The research results in a novel solution to the control synthesis problem for the industrial system. In particular, the research deals with the synthesis of I-P control for a two-loop system in the technological process of a distillation column. This synthesis is carried out using the AIS algorithm, which is the first application of this technique in this specific context. Methodological approaches are proposed to improve the performance of industrial multivariable control systems by effectively using optimization algorithms and establishing modified quality criteria. The numerical performance index ISE justifies the effectiveness of the AIS-based controllers in comparison with conventional PID controllers (ISE₁ = 1.865, ISE₂ = 1.56). The problem of synthesis of the multi-input multi-output (MIMO) control system is solved, considering the interconnections due to the decoupling procedure.

The broad emission bump in the electromagnetic spectra observed following the detection of gravitational waves created during the kilonova event of merger of two neutron stars in August 2017, GW170817, has been linked to the heavy elements of lanthanides (Z=57-71), and a new understanding of creation of heavy elements in the r-process. The initial spectral emission bump has a wavelength range of 3000 - 7000 \AA, thus covering the region of ultraviolet (UV) to optical (O) wavelengths, and is similar to those seen for lanthanides. Most lanthanides have large number of closely lying energy levels which introduce extensive sets of radiative transitions which often form broad region of lines of significant strength. The current study explores these broad features through photoabsorption spectroscopy of 25 lanthanides ions, Ho I-III, Er I-IV, Tm I-V, Yb I-VI and Lu I-VII. With excitations only to a few orbitals up beyond the ground configurations, we find most of these ions cover large number of bound levels with open $4f$ orbital and produce tens to about hundred thousands lines that may form one or multiple broad features in X-ray to UV, O, and infrared (IR) regions. Spectrum of each of 25 ions is presented indicating presence, shape and wavelength region of the features. Accuracy of atomic data to interpret the merger spectra has been a outstanding problem. The present study aims at providing improved atomic data for energies and transition parameters obtained using relativistic Breit-Pauli approximation implemented in the atomic structure code SUPERSTRUCTURE. The present data have been benchmarked with available experimental data for energies and transition parameters. The study finds that number of ions under the present study are possible contributors of the emission bump of GW170817. All atomic data will be made available online at NORAD-Atomic-Data database.

The article presents several innovative systems developed through student laboratory projects, including two autonomous vehicles, a four-legged walking robot, an active ankle-foot orthosis, a ball on beam balancing mechanism, a ball on plate system, and a manipulator arm—all powered by pneumatic artificial muscles (PAMs). Fluidic muscles offer significant potential in various mechatronic systems, robots, and manipulators due to their flexible, lightweight nature and compliance. Their ability to produce smooth and adaptable motions is particularly beneficial in applications requiring natural and human-like movement, such as rehabilitation and assistive devices. Although PAMs powered control systems face challenges with nonlinear phenomena, their biologically inspired design holds promise for future applications across various industries. These may include innovative applicability in industrial, automotive, and aerospace sectors, as well as use in sports, medical aids, entertainment, and animatronics. Incorporating self-made laboratory systems actuated by PAMs into control systems education offers a comprehensive learning opportunity that combines theoretical concepts with hands-on experience. This approach develops the necessary skills of future engineers, expanding their understanding of technical principles and preparing them for future challenges in engineering practice.

Cirrhosis is a chronic disease with multiple etiologies, multiple manifestations, and multi-organ involvement. Affects about 200 million people worldwide. Its main complication is Portal hypertension (PHT). Cirrhotic cardiomyopathy is a consequence of PHT, with heart failure (HF) being the main manifestation. On the other hand, for people with cardiopathy due to other reasons beyond cirrhosis, the presence of the last could act as a trigger to acute HF. Finally, when HF and cirrhosis coexist, the renal system suffers the most, originating from type-5 cardio-renal syndrome, a complex entity with many challenges in diagnosis and treatment. This entity was recently defined and there is a lack of data on the epidemiology of this syndrome. A 77-year-old woman, with cardiovascular risk factors; heart failure with reduced ejection fraction (HFrEF), secondary ischemic and valvular cardiopathy, chronic Kidney disease (CKD), and stable decompensated cirrhosis, went to the emergency department after progressive abdominal perimeter augmentation, legs’ edema and hematochezia. It was assumed acute decompensated cirrhosis and acute decompensated chronic kidney disease, had triggered digestive bleeding and the patient stayed hospitalized. Intravenous diuretic therapy was started but, the ascites and kidney function got worse, the Nt pro-BNP grew until 1125000 pg/ml, and a transthoracic echocardiography showed important signs of congestion, isolated right ventricular dysfunction, with normal cardiac output. After teamwork’s discussion, a type-5 cardio-renal syndrome was assumed deciding not to act on tricuspid regurgitation due to the maladaptive RV remodeling. Hepatorenal syndrome treatment was begun (oral terlipressin and intravenous albumin), followed by decongestion therapy, resulting in a marked improvement in clinical presentation. The kidney, heart, and liver recovered to these basal states. With this clinical case, the authors want to show how multidisciplinary management is important to face tricuspid regurgitation and right ventricular dysfunction.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

The high-mountain and arctic plants are considered especially sensitive to the climate changes because of close adaptations to the cold environment. Kalmia procumbens, the typical arctic-alpine species reaches southernmost European localities in the Pyrenees and Carpathians. The aim of the study was the assessment and comparison of K. procumbens current potential niche areas in the Pyrenees and Carpathians and their possible reduction due to climate change, depending on the scenario. Realized niches of K. procumbens in the Pyrenees are compact while in the Carpathians dispersed. In both mountain chains, the species occurs in the alpine and subalpine vegetation belts, going down to elevations of about 1500-1600 m, while the most elevated localities in the Pyrenees are at ca 3000 m, about 500 m higher than in the Carpathians. The localities of K. procumbens in the Carpathians have a more continental climate than in the Pyrenees, with lower precipitation and temperatures but higher seasonality of temperature and of precipitation. The species covered a larger area of geographic distribution during Last Glacial, and reduced area during mid Holocene. Due to the climate warming, the strong reduction of potential area of occurrence to 2100 is expected in the Carpathians and moderate reduction in in the Pyrenees.

Flooding and overflows are recurring problems in several Brazilian cities, which usually undergo disorderly development. Their causes vary from increased impervious surface areas, deficiency/inefficiency of drainage structures and their maintenance, siltation of rivers, channel obstructions, and climatic factors. This situation is aggravated in the major cities. The Anhangabau watershed lies in the central portion of the city of Sao Paulo – Brazil and covers a drainage area of 5.4 km². The region is highly urbanized and crossed by a major north-south road connection. During heavy rain events, portions of this interconnection passage become compromised, disrupting the flow of vehicles, creating a chaotic situation for the population, as well as losses to the national economy. Observed rainfall records and an existing IDF (intensity duration frequency) curve for the region are used to obtain design storms. To account for climate change, a well know procedure, the equidistance quantile matching method for updating IDF curves under climate change, was applied to the existing historical data. Several different global climate models (GCM) and one regional model were applied to obtain and update rainfall design storm. The GCMs and future scenarios used were from the IPCC Assessment Report 5 (AR5) and two future projections: RCP (representative concentration pathway) 4.5 and 8.5. Alternatives previously proposed to solve to flooding issue are briefly reviewed. On one of the latest studies [1], a few modern concepts of water resources management are presented, and the linear retention measure was found to offer higher potential to mitigate the flooding problem in the lower valley of the watershed. Therefore, this alternative was used to evaluate different design storms scenarios combined with return periods of 25 and 100-years as well as the updated IDF under climate change for RCP 4.5 and RCP 8.5. To model the complex network, representing both road and drainage systems and their interconnections, PCSWMM/SWMM software was applied. Results are presented as flooding maps and show the impacts of the proposed linear retention measure based on the existing IDF curves and the updated IDF curves under climate change for two different drainage system conditions, current and improved with the use of linear retention reservoirs. Results show that the prosed changes on the drainage system help reduce the risk and damage to flooding. The climate change scenarios, however, impose a significant threat and need immediate attention from city planners and stakeholders.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

Epithelial ovarian cancer is an aggressive disease of the female reproductive system and a leading cause of cancer death in women. Standard of care includes surgery and platinum-based chemotherapy yet patients continue to experience a high rate of recurrence and metastasis. Hyperthermic intraperitoneal chemotherapy (HIPEC) treatment in highly selective patients extends overall survival by nearly 12 months. The clinical studies are highly supportive of the use of HIPEC in the treatment of ovarian cancer though the therapeutic approach is limited to academic medical centers. The mechanism underlying HIPEC benefit remains unknown. The efficacy of HIPEC therapy is impacted by several procedural and patient/tumor factors including the timing of surgery, platinum sensitivity, and molecular profiling such as homologous recombination deficiency. The present review aims to provide insight into the mechanistic benefit of HIPEC treatment with a focus on how hyperthermia activates the immune response, induces DNA damage and impairs DNA damage repair pathways, and has a synergistic effect with chemotherapy, with the ultimate outcome of increasing chemosensitivity. Identifying the points of fragility unmasked by HIPEC may provide the key pathways that could be the basis of new therapeutic strategies for ovarian cancer patients.

The serendipitous discovery of antiparasitic drugs, such as quinine and artemisinin from plant origin reveals that the search for new chemical pharmacophores from medicinal plants is valuable. The present study sought to explore the antiplasmodial, antileishmanial, and antitrypanosomal activities of extracts from Lippia adoensis. Crude extracts of L. adoensis leaves and twigs, which were obtained by extraction using 70% ethanol in water, were assayed for antiplasmodial activity against P. falciparum 3D7 and Dd2 through the SYBR green I-based fluorescence assay; and for antileishmanial, antitrypanosomal, and cytotoxic effects on Leishmania donovani, Trypanosoma brucei brucei, and Vero cells, respectively, using the resazurin colorimetric assays. The phytochemical analysis of the extracts was performed using a liquid chromatography-mass spectrometry (LC-MS) feature-based detection and molecular networking flow on Global Natural Product Social (GNPS). As a result, the crude extracts from L. adoensis inhibited growth of P. falciparum (3D7 and Dd2) (IC50s; (3D7): 10.008 and 97.467 μg/mL; (Dd2): 29.48 and 26.96 μg/mL), L. Donovani (IC50s: 22.879-10.522 μg/mL), and T. brucei brucei (IC50s: 2.3085-55.06 μg/mL). The extracts were found to be non-cytotoxic to Vero cells, thus yielding median cytotoxic concentrations (CC50s) above 100 μg/mL. The LC-MS tandem molecular networking flow predicted that the extracts contain valsafungin A and bacillamidin on the first cluster, and fatty acids, ketone and aldehyde derivatives on the second cluster. Overall, the present study demonstrated the antiparasitic effects of L. adoensis extracts, thus justifying the use of this plant in the traditional treatment of fever and malaria conditions. Nevertheless, detailed metabolomic studies and antiparasitic mechanisms of action of the extracts are expected to unveil the potential antiparasitic hit compounds.

Celiac disease (CD) is a genetically conditioned autoimmune process that appears in susceptible people. It can affect people of any age, and slightly predominates in females. It has a fairly homogenous global distribution, with an average prevalence of 1-2%, the frequency having increased in recent decades. The only effective treatment is a strict and permanent gluten-free diet (GFD), although the level of compliance with it is poor, at about 50% of cases. To monitor the effectiveness of the GFD, several procedures involving various approaches are employed: a) periodic interviews by nutritionists; b) clinical follow-up; c) serological controls of specific antibodies; d) endoscopies with collection of duodenal biopsies; e) structured questionnaires; f) determination of gluten peptides derived from gluten in feces and/or urine. All of these procedures are useful when applied, alone or in combination, depending on the cases. Some patients will only need to consult to their doctors, while others will require a multidisciplinary approach to assess their compliance with the GFD. In children, normalization of duodenal mucosa was achieved in 95% of cases within 2 years, while it is more delayed in adults, whose mucosa take longer to heal completely.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

The article presents data on phylogeny, genome size, and ploidy of species of the genus Kalidium Moq. in the flora of Kazakhstan. Genus Kalidium belongs to the tribe Salicornieae of the subfamily Salicornioideae of the family Chenopodiaceae and unites 8 species, the main range of which covers the Iranian-Turanian and Central Asian deserts. There are 4 species in the flora of Kazakhstan: K. foliatum, K. caspicum, K. schrenkianum and the recently described K. juniperinum. Populations of species of the genus Kalidium in the saline deserts of Kazakhstan occupy large areas, often forming monodominant communities. Sometimes there is a joint growth of 2 and very rarely 3 species of the genus. During the period of fieldwork (2021-2022), populations were identified in which these species grew together with a predominance, in most cases, of K. caspicum. Samples of representatives from 15 populations were collected for research. Selected plant samples were studied by flow cytometry to determine plant ploidy. Sequencing of nrITS and two chloroplast fragments were used to build a phylogenetic tree, including sequences from the NCBI database., A phylogenetic tree of species of the genus Kalidium was compiled which considers previously published data. In the valley of the middle reaches of the Syrdarya River tetraploid populations of K. caspicum were found. A hybrid between K. foliatum and K. caspicum was found in the Ili River valley (Almaty region, Uigur district). To identify phylogenetic processes at the intraspecific level, the SCoT (Start codon targeted) fingerprinting method was used.

The convective hot air drying technology can cause physicochemical, nutritional, and organoleptic losses in mango (Mangifera indica). Therefore, mango dehydration technologies were compared through a Systematic Literature Review to identify the effects on mango’s physicochemical, nutritional, and organoleptic properties. The bibliographic and theoretical results were analyzed. Of the 76 resulting articles, it was found that the countries with authors who participated most in the scientific production were those related to mango production or importation. Furthermore, the freeze-drying technology allows operating at lower temperatures than convective hot air drying, contributing to the preservation of ascorbic acid, among other compounds. The refractance window has the shortest operation time to obtain moisture values between 10 and 20%. The dehydrated samples using the refractance window are smooth, homogeneous, non-porous, and comparable to the color obtained with freeze-drying, which is acceptable for industrial applications.

In hepatocellular carcinoma (HCC), recurrence usually occurs after curative surgical resection. Currently, no approved adjuvant therapy has been shown to reduce recurrence rates. In this report, the in vivo mouse effect of sequential combination treatment with recombinant mouse interferon-alpha (rmIFN-α) and an anti-mouse-PD1 antibody on hepatitis B virus (HBV) clearance was evaluated. A phase I clinical trial was then conducted to assess the safety, tolerability, and inhibitory activity of sequential therapy with ropeginterferon alfa-2b and nivolumab in HCC recurrence in patients who have undergone curative surgery for HBV-related HCC. In animal modeling, HBV suppression was significantly greater with rmIFN-α and anti-PD1 sequential combination treatment than with their treatment alone. In the Phase I study, eleven patients completed the sequential therapy with ropeginterferon alfa-2b every two weeks at the dose of 450 µg for six doses, followed by three doses of nivolumab every two weeks up to 0.75 mg/kg. A notable decrease or clearance of HBV surface antigen was observed in two patients. Dose-limiting toxicity of grade 3 alanine transaminase and aspartate aminotransferase increases was observed in one patient. The maximum tolerated dose was determined. Currently no HCC recurrence has been observed. The treatment modality was well tolerated. The data support further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC.

Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the formidable challenges and facilitating factors essential for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.

Demography and behavior of Teinopodagrion oscillans was studied in a protected area from Andean region. Adult damselflies were individually marked, and using their recapture histories we estimated survival, longevity, sex ratio, and population size using Cormack-Jolly-Seber models. Furthermore, aspects of their behaviour were recorded. Survival, recapture, and lifespan were similar for both sexes and all age groups. Mature males were larger and the distance from the water was similar for all individuals. The most supported model was the time-dependent model for survival and recapture (Phi(t) p(t)). This suggests that weather variations affect in a significant way the demography of this population. Individuals exhibited high fidelity to their site perch, perching with open wings near to water on a variety of perch. Mature males make short flights from the perch to intercept conspecific and interspecific males and to hunt prey. Tandem position was formed on macrophytes and then the pair flight away. Oviposition lasted for 11.23 minutes on average, with the females ovipositing by abdomen submersion. Our results offer insights on demographic characteristics and behaviour of this species, providing crucial information for short and long term conservation decisions of the biodiversity in ecosystems of the Andean region.

To investigate the process and chemistry of reaction zone formation, we conducted detailed petrographic observations and major-trace element analysis of rocks and minerals of lherzolite xenoliths from basanites of Tumusun volcano (Baikal Rift Zone). The reaction zones gradually disappear from contact toward center of xenoliths. This indicates their formation as a result of lherzolite-basanite interaction. The influence of basanite melt on major-trace element composition of secondary minerals of reaction zones is notable only at distance up to 100-200 μm from the contact. The major-trace element composition of secondary clinopyroxenes from orthopyroxene reaction zone indicates their formation from a melt formed by dissolution of orthopyroxene and influenced by element diffusion from basanite melt. Inside xenoliths the secondary minerals have Mg# values equal to or higher than Mg# of primary minerals. The secondary clinopyroxenes inherit their depleted or enriched REE pattern from primary pyroxenes. The major-trace element variations in secondary clinopyroxenes testify melt heterogeneity. Secondary clinopyroxene has slightly higher LILE and similar abundances of other trace elements compared to unreacted part of clinopyroxene grain. This is consistent with model developed from experimental studies: due to the interaction with basanite, incongruent dissolution of orthopyroxene occurs to form a melt which circulates in lherzolite and leads to pyroxenes and spinel dissolution. Non-dissolved centers of minerals are homogenous and similar in major-trace element composition to primary minerals. The process of peridotite-basanite interaction is not isochemical: even the centers of large xenoliths become enriched in LILE.

The viscoelastic properties and structure parameters have been investigated for aqueous solutions of wormlike micelles of cationic surfactant erucyl bis(hydroxyethyl) methylammonium chloride with long C22 tail in the presence inorganic salt KCl. The salt content has been varied to estimate linear to branched transition conditions due to screening of the electrostatic interaction in the networks. The local cylindrical structure and low electrostatic repulsion was obtained by SANS data. The drastic power law dependencies of rheological properties on surfactant concentrations were obtained at intermediate salt content. Two power law regions were detected in semi-dilute solutions related to “unbreakable” and “living” micellar chains. The fast contour length growth with surfactant concentration was demonstrated that is in good agreement with theoretical predictions.

Diarrhea remains one of the leading causes of mortality worldwide, especially among children. Recent epidemiological studies conducted in developing countries identified Shigella species as the most predominant pathogenic bacteria responsible for diarrhea. Antimicrobial therapy is necessary for Shigella infections; however, the rapid emergence of resistance against existing antimicrobials in Shigella spp. poses a serious global health problem. To identify alternative antimicrobial compounds with activity against Shigella species, the pathogens responsible for bacterial diarrhea. In this study, we have applied antibacterial phenotypic screening to identify potent anti-Shigella compounds across a broad chemical diversity, including selected acetaminophen derivatives containing benzothiazoles backbone, and their combination with certain antibiotics. In continuation to our effort in searching potent antimicrobial compounds, we have found this time around that two acetaminophen derivatives containing benzothiazoles backbone (4a and 4b) could inhibit the growth of Shigella flexneri with common MIC value of 12.5 µg/ml. These compounds were established through a time-kill kinetics’ study to be bactericidal. Meanwhile, the 2-aminobenzothiazoles (1a and 1b) used for the synthesis of compounds 4 (a & b) were found to be poorly active (MIC: 100 µg/ml) against this pathogen. Combination studies of 4a and 4b with the least susceptible antibiotics (ceftriaxone and cotrimoxazole) demonstrated synergistic anti-Shigella activity. The present study demonstrates that the azobenzothiazole dyes 4 (a & b) can be repurposed as potential anti-Shigella compounds, which can serve as scaffolds for the development of new agents against infectious diarrhea caused by Shigella and other enteric pathogens, especially in developing countries.

Objective: To carry out a bibliometric analysis study of systematic reviews and meta-analyses in dentistry, divided into different thematic areas. Material and method: A search was conducted in the Science Citation Index-Expanded on the core collection of Web of Science, they were selected from the area of Dentistry and Oral Surgery and Medicine categories, the data was downloaded on April 20, 2022 and The 100 most cited articles from each of the thematic areas were selected. Results: An increase in this type of articles was observed in the last decade in the areas of pediatric and medical dentistry and oral pathology. The thematic area that received the most citations was periodontics. The two authors with the most citations are Zwahlen, Marcel and Pjetursson, Bjarni Eluar. The countries that receive the most citations are European, along with the USA and China. The topics that are most published in this type of article deal with Cancer with 50 publications, caries treatment with 25 and fluoridation with 1. The entities that finance this type of articles the most are private companies (26.76%). Conclusions: Together with an exponential increase in the number of publications in dentistry, there has been an increase in the number of publications in systematic reviews. The areas publishing the most articles and having the most citations are Periodontics and Implantology, despite the fact that the most studied topic is cancer.

The study of the impact of polyQ expansion driven proteotoxicity on cell metabolism has evi-denced NAD molecule as a central player in regulating metabolic response and cell repair in neurodegeneration. The decline in NAD intracellular levels represents a hallmark of ageing aris-ing from a dysregulation between NAD-consuming and biosynthetic enzymatic reactions in which NMNAT plays a key role. By an integrated bioanalytical and proteomic experimental design, the derangement of NAD metabolism deriving from the accumulation of polyQ-Htt protein has been analysed in Saccha-romices cerevisiae harbouring a 103Q-Htt and compared with wild-type Htt, in absence and in presence of a phenolic extract from EVOO, as a source of antioxidant bioactive compounds. Quantification of NAD and its precursors and proteomic analysis of the differential protein ex-pression has been performed by LC-DAD-MS. Chronological lifespan and NAD homeostasis was strongly impaired by proteotoxic polyQ-Htt, eliciting a depletion of NAD levels and accumulation of NaMN. In parallel a downregulation of Sirt2 expression levels has been observed. Phenolic extract administration had no meaningful ef-fects on NAD replenishment to prevent proteotoxicity. NaMN can represent a biomarker of accel-erated aging, and/or a signaling molecule for cell repair.

Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

In this article, we delve into the intricate behavior of electronic mechanisms underlying NMR magnetic shieldings, σ, in molecules containing heavy atoms such as cadmium, platinum, and mercury. Specifically, we explore PtXn^{−2} (X = F, Cl, Br, I; n = 4, 6) and XCl2 Te2 Y2 H6 (X = Cd, Hg; Y = N, P) molecular systems. It is known that the leading electronic mechanisms responsible for the relativistic effects on σ are well characterized by the linear response with elimination of small components model (LRESC). In this study, we present results obtained from the innovative LRESC-Loc model, which offers the same outcomes as the LRESC model but employs localized molecular orbitals (LMOs) instead of canonical MOs. These LMOs provide a chemist’s representation of atomic core, lone pairs, and bonds. The whole set of electronic mechanisms responsible of the relativistic effects can be expressed in terms of both non-ligand-dependent and ligand-dependent contributions. We elucidate the electronic origins of trends and behaviors exhibited by these di- verse mechanisms in the aforementioned molecular systems. In PtX4^{−2} molecules, the predominant relativistic mechanism is the well-established one-body spin-orbit (σ^SO(1) ) mechanism, while the paramagnetic mass-velocity (σ^Mv ) and Darwin (σ^Dw ) contributing mechanisms also demand con- sideration. However, in PtX6−2 molecules, the σ Mv+ Dw contribution surpasses that of the SO(1) mechanism, thus influencing the overall ligand-dependent contributions. As for complexes con- taining Cd and Hg, the ligand-dependent contributions exhibit similar magnitudes when nitrogen is substituted with phosphorus. The only discrepancy arises from the σ^SO(1) contribution, which changes sign between the two molecules due to the contribution of bond orbitals between the metal and tellurium atoms.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Nowadays, the presence of pathogen-specific antibodies in the blood is widely controlled by a serodiagnostic technique based on the lateral flow immunoassay (LFIA). However, its common one-stage format with an antigen immobilized in the binding zone of a test strip and a nanodis-persed label conjugated with immunoglobulin-binding proteins is associated with risks of very low analytical signals. It is caused by the presence of non-specific immunoglobulins in very large excess to the target antibodies in the tested samples thus decreasing their binding with the detected labels. In this study, the first stage of the immunochromatographic serodiagnosis was carried out in its traditional format using a conjugate of gold nanoparticles with staphylococcal immunoglobulin-binding protein A and an antigen immobilized on a working membrane. At the second stage, a labeled immunoglobulin-binding protein was added, which enhanced the coloration of the bound immune complexes. The use of two separated steps, binding of specific antibodies, and further coloration of the formed complexes allowed a significant reducing the influence of non-specific immunoglobulins on the assay results. The proposed approach was ap-plied for the serodiagnosis using a recombinant RBD protein of SARS-CoV-2. As a result, an in-crease in the intensity of test zone coloration by more than two orders of magnitude was demonstrated, which enabled to significantly reduce false-negative results. When testing a panel of 16 positive and 8 negative serum samples, the diagnostic sensitivity of the LFIA was 62.5% for the common format and 100% for the enhanced format; the diagnostic specificity of both variants was 100%.

Photovoltaic modules should pass series of tests and examinations, verifying the electrical and thermal characteristics of the module, before being released to the market, examining the properties of the modules should undergo appropriate durability and efficiency tests under real outdoor conditions with exposure to climatic conditions and under laboratory conditions. The performance of photovoltaic cells depends on many factors, such as solar irradiance, module operating temperature, installation location, weather conditions and module shading. In this paper, three selected photovoltaic modules were examined using a large-scale steady-state solar simulator. The current-voltage (I-V) characteristics of the photovoltaic modules were experimentally tested and analyzed. The next step was to implement a three-layer artificial neural network model (MLP). The experimental data obtained in the previous step coupled with output data from MLP were then used in global sensitivity analysis (GSA). Experiments carried out on a large-scale stationary solar simulator showed differences between the values declared by the manufacturer and the values obtained from measurements of PV modules. The first module tested achieved the maximum power point greater than that specified by the manufacturer, while the other two showed power drops; it was 85-87% for the second module, and 95-98% for the third, respectively. The performed global sensitivity analysis (GSA) for the MLP model showed that the parameters: eff (22.9) and Voc/V (14.19) have the largest effect on the power-voltage relationship, while U (7.29) has the smallest effect. The usefulness of machine learning (ML) methods in the comparative analysis of PV modules has been proved.

The effect of sonication on the molecular characteristics of poliacrylic acid (Carbopol® Ultrez 10) and its rheological behavior in aqueous dispersions and microgels containing 0.25 wt. % of the polymer was analyzed in this work by rheometry, weight-average molecular weight (Mw) measurements via static light scattering (SLS), Fourier transform infrared (FTIR) spectroscopy and confocal microscopy. For this, the precursor dispersion and the microgels were sonicated in a commercial ultrasound bath at constant power and different times. We observed a softening of the microgel microstructure consisting of a systematic decrease in its shear modulus, yield stress and viscosity with increasing sonication time, while their overall Herschel-Bulkley (H-B) behavior was preserved. SLS measurements evidenced a reduction of Mw of polyacrylic acid with sonication time. Separately, FTIR measurements indicate that sonication produces scission in the C-C links of the Carbopol® backbone, which results in chains with the same chemistry but lower molecular weight. Finally, confocal microscopy measurements revealed a concomitant diminution of the size of the microsponge domains with sonication time, which is reflected in a softer microstructure resulting from reduction of the molecular weight of polyacrylic acid. The present results indicate that both the microstructure and the rheological behavior of Carbopol® microgels, in particular, and complex fluids in general, may be manipulated or tailored by high-power ultrasonication.

Intussusceptive pillars, regarded as a hallmark of intussusceptive angiogenesis, have been described in developing vasculature of many organs and organisms. The aim of this study was to resolve the question about pillar formation and their further maturation employing zebrafish caudal vein plexus (CVP). The CVP development was monitored by in vivo confocal microscopy in high spatio-temporal resolution using the transgenic zebrafish model Fli1a:eGPF//Gata1:dsRed. We tracked back the formation of pillars (diameter ≤4µm) and intercapillary meshes (diameter >4µm) and analysed their morphology and behaviour. Transluminal pillars in the CVP arose by a combination of sprouting, lumen expansion, and/or by creation of intraluminal folds, and those mechanisms were not associated directly with blood flow. The follow-up of pillars indicated that one third of them disappeared between 28-48 hours post fertilisation (hpf) and of the remaining ones only 1/17 changed their cross-section area by >50%. The majority of the bigger meshes (39/62) increased their cross-section area by >50%. Plexus simplification and establishment of hierarchy was dominated by the dynamics of intercapillary meshes, which formed mainly by sprouting angiogenesis. These meshes were observed to grow, reshape, and merge with each other. Our observations suggested an alternative view on intussusceptive angiogenesis in the CVP.

Clove (Syzygium aromaticum L. Myrtaceae) is an aromatic plant widely cultivated in tropical and subtropical countries, rich in volatile compounds and antioxidants such as eugenol, β-caryophyllene, and α-humulene. Clove essential oil has received considerable interest due to its wide application in the perfumery, cosmetic, health, medical, flavoring, and food industries. Clove essential oil has relevant biological activities to human health, including antimicrobial, antioxidant, and insecticide. This review describes the effect of the extraction method (hydrodistillation, steam distillation, ultrasound-assisted extraction, microwave-assisted extraction, cold pressing, and supercritical fluid extraction) on the chemical composition of essential oil and its correlation with their biological activities. Likewise, are summarized the main compounds and their reported biological activities. Furthermore, the main applications in clove essential oil in the food industry are presented. Finally, this review presents the new biological activities such as anti-inflammatory, analgesic, anesthetic, antinociceptive and anticancer, which are beneficial for human health. This review aims to compile the effect of different methods of extracting clove essential oil on chemical composition, food applications, as well as a current description of biological activities of interest to human health. Biological activities have increased interest in research into this essential oil and its future applications in the food or pharmaceutical industry.

The Coronavirus disease 2019 (COVID-19) pandemic began in Jan. 2020 in Wuhan, China with a new coronavirus designated SARS-CoV-2. The principle cause of death from COVID-19 disease quickly emerged as Acute Respiratory Distress Syndrome (ARDS). A key ARDS pathogenic mechanism is the “Cytokine Storm”. This is a dramatic increase in the blood of inflammatory cytokines. In the last 2 years of the pandemic new pathology has emerged in COVID-19 survivors in which a variety of long-term symptoms emerge. This condition is called “Long COVID”. The spike protein on the surface of the virus (target for the new mRNA/DNA vaccines) is composed of joined S1-S2 subunits. Upon S1 bind-ing to the human ACE2 receptor on cells, the S1 subunit is cleaved and the S2 subunit me-diates entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for initiation and/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the spike S1 protein may activate inflammatory sig-naling and cytokine production independent of the virus. Our data support a potential role for spike S1 activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 spike S1 protein in COVID-19 pathogenesis.

Background: Despite advances in the treatment of hepatocellular carcinoma (HCC) over the last few decades, treatment opportunities for patients with HCC remain limited. HCC is the most common form of liver cancer, accounting for approximately 90% of all cases worldwide. Moreover, apart from the current pharmacological interventions, hepatic resection and liver transplantation are the mainstay curative approaches for patients with HCC. Methods: This systematic review included phase I, II, III, and IV clinical trials (CTs) and randomized controlled trials (RCTs) on current treatments for patients with HCC in an Asian population (2013–2023). A total of 427 articles were screened, and 184 non-duplicate publications were identified. After screening titles and abstracts, 96 publications were excluded, and another 28 were excluded after full-text screening. The remaining 60 eligible RCTs/CTs were finally included. Results: Sixty clinical trials fulfilled our inclusion criteria and screened 36 drugs as monotherapy or combination therapy for HCC. Most studies used sorafenib alone or in combination with any of the treatment regimens. Lenvatinib or atezolizumab with bevacizumab was used for HCC after initial sorafenib treatment. Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. Conclusion: This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicated that sorafenib alone or in combination with atezolizumab and bevacizumab has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in an Asian population

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

Mechanisms for somatic chromosomal mosaicism (SCM) and chromosomal instability (CIN) are incompletely understood. During SNP-array molecular karyotyping and bioinformatic analyses of children with neurodevelopmental disorders and congenital malformations (n=612), we observed colocalizaion of regular chromosomal imbalances or copy number variations (CNV) with mosaic ones (n=47 or 7.7%). Analyzing molecular karyotyping data and pathways affected by CNV burdens, we proposed a mechanism for SCM/CIN, which had been designated as “chromohelkosis” (from the Greek chromosome ulceration/open wound). Briefly, structural chromosomal imbalances are likely to cause local instability (“wreckage”) at the breakpoints, which results either to partial/whole chromosome loss (e.g. aneuploidy) or elongation of duplicated regions. Accordingly, a function for classical/alpha satellite DNA (protection from the wreckage towards the centromere) has been hypothesized. Since SCM and CIN are ubiquitously involved in development, homeostasis and disease (e.g. prenatal development, cancer, brain diseases, aging), we have metaphorically (ironically) designate the system explaining chromohelkosis contribution to SCM/CIN as the cytogenomic “theory of everything” like the homonymous theory in physics inasmuch as it might explain numerous phenomena in chromosome biology. Recognizing possible empirical and theoretical weaknesses of this “theory”, we nevertheless believe that studies of chromohelkosis-like processes are required to understand structural variability and flexibility of the genome.

Crystalline silver thin layers were obtained by high-energy pulsed laser ablation without heating of the deposition substrate. The fluid Plateau-Rayleigh (PRI), Rayleigh – Taylor (RTI) and Richtmyer – Meshkov (RMI) instabilities, as well as crown splash induced during pulsed laser deposition (PLD) in high energy regime, resulting in ring and pearl shaped structures, offer the benefit of increased sorption surface. These morphological structures obtained for the silver thin layers make them of interest for catalytic applications. The study presented with this work addresses both the fundamental and applied issues on the morphological structures obtained for the silver thin layer and their catalytic function in organic processes. In this sense, the catalytic action of the thin silver layer was highlighted by modifications of the Reactive Blue 21 dye (C.I.) in aqueous solution with sodium bicarbonate. Specific investigations and analyzes were carried out by electron microscopy and elemental analysis (SEM-EDX), atomic force microscopy (AFM) and profilometry, mass spectrometry, ablation plasma diagnosis, diffractograms (XRD), as well as IR spectroscopy (FTIR). In addition to the experimental investigation and analyzes, simulation of the ionization energy threshold was conducted in COMSOL for complementary evaluation on the involved processes and phenomena.

Purpose: this paper evaluates the effect of thermo-formed aligners with complementary biomechanical attachments (CBA) on periodontal ligaments (PDL) during the expansion process of the maxillary arch using simulations based on the finite element method (FEM). Methods: four types of teeth (canine 3, premolar 4, premolar 5 and molar 6) were modeled using 3D CAD. In addition, aligners, CBAs and PDL were also 3D modeled. With this information, a FEM model was generated, and a clinical rehabilitation scenario was simulated. For the validation of the results, a comparison with medical records was performed. Results: for canine 3, the displacement was 0.134 mm with a maximum stress of 4.822 x10-3MPa in the amelocemental junction. For premolar 4, the displacement was 0.132 mm at a maximum stress of 3.273x10-3MPa in the amelocemental junction. Premolar 5 had a displacement of 0.129 mm and a stress of 1.358 x10-3MPa at 1 mm from the amelocemental junction. Molar 6 had a displacement of 0.124 mm and a maximum stress of 2.440 x10-3MPa. Conclusions: The simulations showed that the use of CBA reduces tooth tipping. The model with Vestibular CBA presented the best results in terms of the dental movement of expansion of the maxillary arch with the use of thermoformed aligners. Significance: Considering the difficulty of performing in vivo tests that evaluate the configuration effectiveness of the different CBA alternatives in thermoformed aligners, FEM techniques were used to reduce time and costs, and get accurate results with minimal errors.

The construction industry is responsible for 40 to 45% of primary energy consumption in Europe alone. Therefore, it is essential to find new materials with a lower environmental impact in order to attain sustainable housing. This study aims to determine and compare the environmental impact of two clay samples forming a basis for the manufacture of traditional brick, a standard material in building construction; traditional red clay brick and a brick based on clay mixed with a biological ingredient. The samples of fired clay were manufactured at the laboratory scale, the results being valid exclusively as indicators for the extrapolation of the analysis to other studies. The results of the environmental impact of these formulations have been examined through an evaluation of life-cycle analysis (LCA), observing that the incorporation of biological pore forming agents led to a decrease of around 15 to 20% of all impact categories studied. Thus, the suitability of using biological-based additives in clay bricks was confirmed both for their constructive characteristics (lighter material) and increased energy efficiency (better thermal insulation) considering the environmental point of view.

The Upper Hunter Valley is a major coal mining area containing approximately 40% of the currently identified total coal reserves in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. This paper summarises the spatial and temporal variability modes of PM10 pollution in the region, based on long-term multi-site monitoring data and the application of the rotated principal component analysis (RPCA) and wavelet analysis techniques. RPCA identified two distinct air quality clusters/subregions in the valley, one in the west/northwest, the other in the southeast. Wavelet analysis revealed the annual cycle to be most persistent temporal mode of PM10 variability in both subregions, with intermittent signals observed at time scales of around 120, 30~90 and under 30 days. How these variation modes are related to the effects of local PM10 emissions and the influence of meteorology at different time scales deserves further attention in future work. The findings will be used in air quality reporting and forecasting in NSW. The methodology and results can also be useful for air quality research in similar regions elsewhere.

(1) Background: A wide literature based on loading and unloading bending tests has been carried out over the half past century for assessing the force released by superelastic wires. The aim of this investigation is not only to characterize a broadly described superelastic NiTi and a novel CuNiTi archwire, but also to provide novel insights into the load vs deflection profiles. A harmonic scenario for superelastic wires will be shown as temperature is kept constant at 37°C. However, a completely different picture will be highlighted as a temporary heating step up to 50°C is introduced within the force vs deflection profiles. (2) Methods: A variety of NiTi and a novel CuNiTi round and rectangular cross-section archwires have been investigated. Static 3-point bending tests up to a deflection level of 3.0 mm have been carried out for detecting the unloading force plateau levels occurring at 37°C. A hold deflection step of 5 min at deflection levels occurring along the unloading plateau extension is introduced. The effect of a temporary heating up to 50°C on the force plateau level released by the investigated wires is analyzed. (3) Results: Mechanical profiles suggest that the plateau force levels detected at 37°C are consistent with those broadly reported in the literature, but they only represent a single block puzzle of the force scenario that a superelastic wire releases during the orthodontic treatment. (4) Conclusions: Once a superelastic wire is bent and clinically applied, the effect of a temporary heating up to 50°C (e.g. hot food or drink ingestion) produces a significant plateau force increase whose magnitude depends on the deflection level. The highest force increase of about 50% and 40% have been detected at deflection levels located at the beginning of the unloading plateau extension for NiTi and CuNiTi wires, respectively.

“Pecorino” is a typical semi-hard cheese obtained with raw or heat-treated sheep milk using procedures to valorize the raw material's chemical and microbiological properties. In the present study, using a high throughput method of 16S rRNA gene sequencing, we assessed the evolution of the microbiome composition from milk to Pecorino cheese in artisanal processes using milk from Comisana and Lacaune sheep breeds. The comparative analysis of the bacterial com-munity composition revealed significant differences in the presence and abundance of specific taxa in the milk microbiome of the Comisana and Lacaune breeds. NGS analysis also revealed differences in the curd microbiome related to dairy farming practices, which have a relevant effect on the final structure of the Pecorino-cheese microbiome.

MicroRNAs are small non-coding RNAs, which contribute to the regulation of many physiolog-ical and pathological processes. Conventionally, miRNAs perform their activity in the cyto-plasm, where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. MiRNAs recruit to these regions dif-ferent protein complexes, resulting both in activation or repression of transcription, through a number of molecular mechanisms. Haematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs may af-fect gene expression also acting on nuclear mRNA processing and on the biogenesis of miRNA themselves by regulating pri-miRNA maturation. Overall, nuclear miRNAs are biologically ac-tive molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions

The Albufera of Valencia is a coastal lagoon located in the western area of the Mediterranean Sea, in the Iberian Peninsula. It has an area of 23.1 km2 and an average depth of only 1 m, with a maximum depth of 1.6 m. This lagoon is the rest of an original and more extensive wetland of about 220 km2, mostly dedicated to rice cultivation nowadays. Surface water is supplied through several main and many secondary canals for a total of 64 water entry points and three exit points to the sea. It is difficult to evaluate the renewal rate due to the lack of reliable measurements of the inflow or outflow, as well as continuous measurements. Between 1988 and 2018 several procedures have been used, synthesizing in this work the result, in which it is observed a decrease of the inflow in these thirty years, and therefore the residence time is increasing. There is a temporal variation during the year of renewal influenced by rainfall and cultivation periods. Likewise, it is observed that the natural hydrological zoning of the lagoon causes a spatial heterogeneity with small areas with more renewal, practically weekly, and large extensions with little renewal during months. It is impossible to know this information if flow measurements are not taken in each of the main watercourses.

Most cervical cancer cases are a result of persistent high-risk Human papillomavirus (HPV) infections. Cervical cancer is prevalent in LMICs especially in SSA where it is second most prevalent cancer. In South Africa, it is the second most common cancer affecting women aged between 15 and 44 years. The host immune response has been shown as an important factor in controlling the progression or regression of high-risk HPV infection of the cervix to cervical cancer. The risk of cervical cancer is known to be influenced by the host's genetic diversity, particularly by immune response-regulating genes such as the Human Leukocyte Antigen (HLA) class I and II genes. HLA class I genes present viral peptides to CD8+ T cells which are restricted and pre-programmed for cytotoxic functions. There is very little known about the HLA genes of South African women and how these influence outcome of HPV infections. This review aims to understand the role and influence of HLA class I genes in HPV clearance, persistence, and CD8+ T cell mediated immunity in African women by examining existing literature in this area. Understanding this role can influence and inform therapeutic vaccine design that is population specific.

One of the oldest problems in physics is that of calculating the motion of N particles under a specified mutual force: the N-body problem. Much is known about this problem if the specified force is non-relativistic gravity, and considerable progress has been made by considering the problem in one spatial dimension. Here I review what is known about the relativistic gravitational N-body problem. Reduction to one spatial dimension has the feature that gravitational radiation is absent, thereby allowing for a clear comparison between the physics of one-dimensional relativistic and non-relativistic self-gravitating systems. After describing how to obtain a relativistic theory of gravity coupled to N point particles, I discuss in turn the 2-body, 3-body, 4-body, and N-body problems. Quite general exact solutions can be obtained for the 2-body problem, unlike the situation in general relativity in 3 spatial dimensions for which only highly specified solutions exist. The 3-body problem exhibits mild forms of chaos, and provides one of the first theoretical settings in which relativistic chaos can be studied. For N4 other interesting features emerge. Relativistic self-gravitating systems have a number of interesting problems awaiting further investigation, providing us with a new frontier for exploring relativistic many-body systems.

Mexico´s inhabitants have approximately 7 million dogs and cats as pets, of which there is no accurate information about their environmental impacts as a result of their feeding and comfort requirements. The objective of this study is to compare the environmental footprint between a dog and a cat in a family environment. For this purpose, a life cycle analysis was performed including, among other factors, its feeding and waste management in one year of life. Different environmental indicators including the carbon footprint were considered. It was found that the equivalent CO2 emission of a dog is twice that estimated for a domestic cat and that the main contribution is due to the food production. The ecological footprint that is generated when satisfying the requirements for pet´s well-being impacts in the environment contributes primarily to the carbon footprint.

Drosophila melanogaster serves as a important research model both for genetic investigations and for the study of metal toxicity, facilitating the elucidation of physiological mechanisms comparable to those of human organisms. In our research, we evaluated the toxicity effect resulting from exposure to various concentrations of lead and copper on the prolificity rates throughout the life cycle (egg-adult) of four genotypes of Drosophila melanogaster: wild-type (control), white, brown, and white-vestigial. During our study, the prolificity rates were examined across three repetitions under the impact of exposure to concentrations of 0.50, 1.00, 2.00, and 4.00 mM of copper (CuSO₄) and lead (Pb(C₂H₃O₂₎₂). Prolificity rates throughout the life cycle exhibited variations as a direct consequence of genetic factors, the concentration of exposure, and the specific type of metal, either copper or lead. The mutant white-vestigial genotype revealed an IC₅₀ concentration for prolificity inhibition at lower doses of 2.00 mM for copper and 4.00 mM for lead, in contrast to the control genotype (wild-type), which exhibited an inhibition concentration rate >IC₅₀ of 4.00 mM only in the case of copper. Our results concluded that the (i) dose influences the prolificity rate in a directly proportional manner, (ii) comparative analyses between copper and lead revealed that copper displayed toxicity across all genotypes within the concentration range of 0.50 mM to 2.00 mM. In contrast, lead exhibited toxicity within the concentration range of 1.00 mM to 4.00 mM, highlighting a (iii) more acute toxicity characteristic in the case of copper. Thus, the results of this research reflect the importance of using Drosophila melanogaster as a genetic model in the comparative study of the interaction between genetic factors and the toxicity of metals, offering significant insights into monitoring their impact and defining the maximum permissible doses on organisms.

Organisms are adapted to each other and the environment, not as tradition would have it, because natural selection made them that way, but because there is inbuilt striving towards stability and equilibrium. A General Theory of Behaviour connects imagery, affect and action with the central executive system we call Consciousness. The General Theory is founded on the assumption that the primary motivation of all of Consciousness and intentional behaviour is Psychological Homeostasis. Psychological homeostasis is as important to the organisation of mind and behaviour as Physiological Homeostasis is to the organisation of bodily systems. Consciousness processes quasi-perceptual images independently of the input to the retina and sensorium. Consciousness is the “I-Am” control centre for integration and regulation of (my) thoughts, (my) feelings and (my) actions with (my) conscious mental imagery as foundation stones. Imagery vividness, a combination of clarity and liveliness, is essential to imagining, remembering, thinking, predicting, planning and acting. Assessment of vividness using introspective report is validated by objective means such as fMRI. A significant body of work shows that vividness of visual imagery is determined by the similarity of neural responses in imagery to those occurring in perception of actual objects and performance of activities. I am Conscious, therefore I am.

GeneVac-B® was recently licensed in Burkina Faso and is widely used for population vaccination. This study aimed to evaluate the immune response in people fully vaccinated against hepatitis B with the GeneVac-B® vaccine in Burkina Faso under actual conditions of use. This cross-sectional study included individuals fully vaccinated with GeneVac-B®. For each consenting participant, sociodemographic and clinical data were collected using a structured questionnaire. Approximately 4 mL of whole blood was collected for immunological (anti-HBs, HBsAg, anti-HCV and anti-HIV) and biochemical (blood glucose, total cholesterol, and triglycerides) testing. The anti-HBs titer was used to determine the immune response. A total of 392 participants were included in the study. The mean age was 35.5±15 years. Approximately 56.1% had been previously exposed to HBV. Three hundred eighty (380) participants had an anti-HBs titer ≥ 12 mIU/mL, a seroprotection rate of 96.9%, and 12 had a titer &lt; 12 mIU/mL, a nonresponse rate of 3.1%. Among the nonresponders, 11 (11/12; 91.7%) had high total cholesterol levels (&gt; 240 mg/dL), and 8 (8/12; 66.7%) were older than 40 years of age. The results showed an excellent immune response to GeneVac-B® in our study population. However, age &gt; 40 and high total cholesterol appear to be factors associated with nonresponse.

Here we present 1. a model for amplicon sequencing 2. a definition of the best assignment of a read to a set of reference sequences 3. strategies and structures for indexing reference sequences and computing the best assign- ments of a set of reads efficiently, based on (ultra)metric spaces and their geometry The models, techniques, and ideas are particularly relevant to scenarios akin to 16S taxonomic profiling, where both the number of reference sequences and the read diversity is considerable.

Dengue is a viral mosquito-borne disease that rapidly spreads in tropical and subtropical countries, including the Philippines. One of its most distinguishing characteristics is the ability of the Dengue Virus (DENV) to easily surpass the innate responses of the body, thus activating B cells of the adaptive immunity to produce virus-specific antibodies. Moreover, Dengvaxia® is the only licensed vaccine for DENV, but recent studies showed that seronegative individuals become prone to increased disease severity and hospitalization. Owing to this limitation of the dengue vaccine, this study determined and compared consensus and unique B cell epitopes among each DENV (1-4) Philippine isolate to identify potential areas of interest for future vaccine studies and therapeutic developments. An in silico-based epitope prediction of forty (40) DENV 1-4 strains, each serotype represented by ten (10) sequences from The National Center for Biotechnology Information (NCBI), was conducted using Kolaskar and Tongaonkar antigenicity, Emini surface accessibility, and Parker hydrophilicity prediction in Immune Epitope Database (IEDB). Results showed that five (5) epitopes were consensus for DENV-1 with no detected unique epitope, one (1) consensus epitope for DENV-2 with two (2) unique epitopes, one (1) consensus epitope for DENV-3 plus two (2) unique epitopes, and two (2) consensus epitopes and one (1) unique epitope for DENV-4. The findings of this study would contribute to determining potential vaccine and diagnostic marker candidates for further research studies and immunological applications against DENV (1-4) Philippine isolates.

Gardasil 4, a human papilloma virus vaccine, has been shown to protect against various cancers, including cervical cancer. Common side effects include injection site pain, fever, headaches, and muscle aches. In some individuals, the severe side effect of postural orthostatic tachycardia syndrome (POTS) has been reported. POTS is characterized by the abnormal response of lightheadedness, blurry vision, and dizziness while transitioning to an upright posture. POTS predominately affects women, with more than eighty-five (85) percent of POTS patients being female. POTS on average, takes five years and eleven months to receive the diagnosis. Additionally, ​A strong association between POTS and Ehlers Danlos Syndrome Type III (EDS) exists. Eighty (80) percent of patients with EDS have POTS. This severe side effect dictates that providers need to be aware of this strong association of HPV vaccinations and POTS. ​In this report we will present a case of a young women with a past medical history significant for EDS type III who was diagnosed with POTS after receiving Gardasil 4 vaccination. This case demonstrates the need for physicians to be aware of the association of POTS with EDS type III and HPV vaccination. Physician awareness of the associations, signs and symptoms of POTS and earlier testing at the first presentation of signs and symptoms will limit the negative impact on patient’s quality of life.

DIEP-based breast reconstruction necessitates wide undermining at the abdominal donor-site, creating large wound areas. Flap harvesting is usually conducted using electrosurgical dissection devices. This study sought to compare the clinical outcomes in patients after using the PEAK PlasmaBlade (PPB) versus monopolar electrocautery (MPE). This retrospective cohort study included 128 patients with DIEP-based breast reconstruction. Patient characteristics as well as information on the postoperative course were collected and a comparative evaluation was conducted. The MPE group exhibited significantly (p* = 0.0324) higher abdominal drainage volume (351.11 ± 185.96 ml) compared to the PPB group (279.38 ± 183.38 ml). Subgroup analysis demonstrated that PPB significantly reduced postoperative wound fluid in patients with BMI > 30 kg/m² (p* = 0.0284), without prior neoadjuvant chemotherapy (p** = 0.0041), and among non-smokers (p = 0.0046). Furthermore, postoperative pain was significantly (p**** < 0.0001) lower in the PPB cohort. This study confirms the non-inferiority of the PEAK PlasmaBlade to conventional electrocautery for abdominal flap harvesting. The PPB demonstrated advantages, notably reduced drainage volume and lower postoperative pain levels. Recognizing patient subsets that benefit more from the PPB highlights the importance of personalized device selection based on patient characteristics.