Mobility as a Service (MaaS) is an innovative transport concept, anticipated to provide travelers with different kinds of travel services, more sustainable than a private car, in a simpler, packaged way. It combines different transport modes to offer a tailored mobility package, like a monthly mobile phone contract. The rapid development of intelligent transportation system and the shared economy has speeded up the development of MaaS in these years. In this paper, we aim at classifying the existing research on MaaS and the characteristics of MaaS into different categories, in order to answer the following questions after reviewing the existing literature: What is MaaS? Who are the main actors in MaaS? How can MaaS be implemented? Why should it be implemented? Where will MaaS end up in this wave of disruption? When we talk about MaaS, what are we focusing on? What is the future leading frequency of MaaS? Finally, based on the existing literature, we envision the leading future of MaaS.

Dewetting transition - a concept borrowed from fluid mechanics - is a physiological process which takes place inside the hydrophobic pores of ion channels. This transient phenomenon causes a metastable state which forbids water molecules to cross the microscopic receptors’ cavities. This leads to a decrease of conductance, a closure of the hole and, subsequently, severe impairment of cellular performance. We suggest that artificially-provoked dewetting transition in ion channels’ hydrophobic pores could stand for a molecular candidate to erase detrimental organisms, such as viruses, bacteria and cancer cells. We describe a novel type of high-affinity monoclonal antibody, which: a) targets specific trans-membrane receptor structures of harmful or redundant cells; b) is equipped with lipophilic and/or hydrophobic fragments that prevent physiological water flows inside ion channels. Therefore, we achieve an artificial dewetting transition inside receptors’ cavities which causes transmembrane ionic flows discontinuity, channel blockage and subsequent damage of morbid cells. As an example, we describe dewetting monoclonal antibodies targeting the M2 channel of the Influenza A virus: they might prevent water to enter the pores, thus leading to virion impairment.

Rotavirus is a major cause of diarrhea globally in animals and young children under 5 years. Here, molecular detection and genetic characterization of porcine rotavirus in smallholder and commercial pig farms in the Lusaka Province of Zambia were con-ducted. Screening of 148 stool samples by RT-PCR targeting the VP6 gene revealed a prevalence of 22.9 % (34/148). Further testing of VP6-positive samples with VP7-specific primers produced 12 positives, which were then Sanger-sequenced. BLASTn of the VP7 positives showed sequence similarity to porcine and human rota-virus strains with identities ranging from 87.5% to 97.1%. By next-generation se-quencing, the full-length genetic constellation of the representative strains RVA/pig-wt/ZMB/LSK0137 and RVA/pig-wt/ZMB/LSK0147 were determined. Geno-typing of these strains revealed a known Wa-like genetic backbone and their genetic constellations were G4-P[6]-I5-R1-C1-M1-A8-N1-T1-E1-H1 and G9-P[13]-I5-R1-C1-M1-A8-N1-T1-E1-H1, respectively. Phylogenetic analysis revealed that these two viruses might have their ancestral origin from pigs, though some of their gene segments were related to human strains. The study shows evidence of reas-sortment and possible interspecies transmission between pigs and humans in Zambia. Therefore, the “One Health” surveillance approach for rotavirus A in animals and humans is recommended to inform the design of effective control measures.

This paper shows that by applying the Nyquist-Shannon sampling theorem, the spatial and temporal resolution of a simulation can be no more than half the resolution of the simulating reality. This has significant implications for not only the values of the observables in the simulation but also its physical laws. This progressive halving of nested simulations coupled with the minimum resolution compatible with the production of a simulation also sets a limit to the nestedness of a lineage of simulations (it is by no means infinite). The limit of nestedness is then used to calculate the probability that we are living in a simulation assuming a single base reality. This will be shown to be significantly lower than popular expectation. A Kardashev-like scale, with three variants, is also developed to gauge the technological advancement of a civilization in relation to the extent to which it can extract information from space and time.

It has been widely described that chronic intake of fructose causes metabolic alterations which can be associated with brain function impairment. In this study, we evaluated the effects of fructose intake on the sleep-wake cycle, locomotion and neurochemical parameters in Wistar rats. The experimental group was fed with 10% fructose in drinking water for five weeks. After treatment, metabolic indicators were quantified in blood. Electroencephalographic recordings were used to evaluate the sleep architecture and the spectral power of frequency bands. Likewise, the locomotor activity and the concentrations of orexin A and monoamines were estimated. Our results show that fructose diet significantly increased the blood levels of glucose, cholesterol, and triglycerides. Fructose modified the sleep-wake cycle of rats increasing the waking duration and conversely decreasing the non-rapid eye movement sleep. Furthermore, these effects were accompanied by increases of the spectral power at different frequency bands. Chronic consumption of fructose caused a slight increase in the locomotor activity as well as an increase of orexin-A and dopamine levels in the hypothalamus and brainstem. Specifically, immunoreactivity for orexin-A was increased in the ventral tegmental area after the intake of fructose. Our study suggests that fructose induces metabolic changes and stimulates the activity of orexinergic and dopaminergic neurons which may be responsible for alterations of the sleep-wake cycle.

In the present study, we studied the effect of apolipoprotein A-1 (APOA1) on the spatial and molecular characteristics of bone marrow adipocytes, using well-characterized ApoA1 knockout mice. APOA1 is a central regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, and thus HDL; our recent work showed that deficiency of APOA1 increases bone marrow adiposity in mice. We found that ApoA1 deficient mice have greatly elevated adipocytes within their bone marrow compared to wild type counterparts. Morphologically, the increased adipocytes were similar to white adipocytes, and displayed proximal tibial-end localization. Marrow adipocytes from wild type mice were significantly fewer and did not display bone-end distribution pattern. The mRNA levels of the brown/beige adipocyte-specific markers Ucp1, Dio2, Pat2, Pgc1a, and the expression of leptin were greatly reduced in the ApoA1 knock-out in comparison to the wild-type mice. In the knock-out mice adiponectin was remarkably elevated. In keeping with the close ties of hematopoietic stem cells and marrow adipocytes, we found that the elevated adiposity in the ApoA1 knock out mice is associated with a significant reduction of the hematopoietic stem cells and common myeloid, but not common lymphoid, progenitors. Moreover, the “beiging”-related marker osteopontin and the angiogenic factor VEGF were also reduced in the ApoA1 knock-out mice, further supporting the notion that APOA1, and most probably HDL-C, regulate bone marrow microenvironment, favouring beige/brown adipocyte characteristics.

Translation is spatiotemporally regulated and ER-associated mRNAs are generally in efficient translation. It is unclear whether the ER-associated mRNAs are deadenylated or degraded on the ER surface in situ or in the cytosol. Here, we showed that ER possessed active deadenylases, particularly the poly(A)-specific ribonuclease (PARN), in common cell lines and mouse tissues. Consistently, purified recombinant PARN exhibited a strong ability to insert into the Langmuir monolayer and liposome. ER-anchored PARN was found to be able to reshape the poly(A) length profile of the ER-associated RNAs by suppressing long poly(A) tails without significantly influencing the cytosolic RNAs. The shortening of long poly(A) tails did not affect global translation efficiency, suggesting that the non-specific action of PARN towards long poly(A) tails was beyond the scope of translation regulation on the ER surface. Transcriptome sequencing analysis indicated that the ER-anchored PARN trigged the degradation of a small subset of ER-enriched transcripts. The ER-anchored PARN modulated the translation of its targets by redistributing ribosomes to heavy polysomes, suggesting that PARN may play a role in dynamic ribosome reallocation. During DNA damage response, MK2 phosphorylated PARN-Ser557 to modulate PARN translocation from the ER to cytosol. By promoting the decay of ER-associated MDM2 transcripts with low ribosome occupancy, the ER-anchored PARN modulated DNA damage response and thereby cell viability. These findings revealed that a highly regulated communication between mRNA degradation rate and translation efficiency is present on the ER surface in situ and that PARN may contribute to this communication by modulating the dynamic ribosome reallocation between transcripts with low and high ribosome occupancies.

We present a new interpretation of the Higgs field as a composite particle made up of a positive, with, a negative mass Planck particle. According to the Winterberg hypothesis, space, i.e., the vacuum, consists of both positive and negative physical massive particles, which he called planckions, interacting through strong superfluid forces. In our composite model for the Higgs boson, there is an intrinsic length scale associated with the vacuum, different from the one introduced by Winterberg, where, when the vacuum is in a perfectly balanced state, the number density of positive Planck particles equals the number density of negative Planck particles. Due to the mass compensating effect, the vacuum thus appears massless, charge-less, without pressure, energy density, or entropy. However, a situation can arise where there is an effective mass density imbalance due to the two species of Planck particle not matching in terms of populations, within their respective excited energy states. This does not require the physical addition or removal of either positive or negative Planck particles, within a given region of space, as originally thought. Ordinary matter, dark matter, and dark energy can thus be given a new interpretation as residual vacuum energies within the context of a greater vacuum, where the populations of the positive and negative energy states exactly balance. In the present epoch, it is estimated that the dark energy number density imbalance amounts to, , per cubic meter, when cosmic distance scales in excess of, , are considered. Compared to a strictly balanced vacuum, where we estimate that the positive, and the negative Planck number density, is of the order, particles per cubic meter, the above is a very small perturbation. This slight imbalance, we argue, would dramatically alleviate, if not altogether eliminate, the long standing cosmological constant problem.

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. The anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of lead compounds was confirmed using lipopolysaccharide (LPS) treated blood to mimic conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood.

The Vaal Dam catchment, which is the source of potable water for Gauteng province, holds various human activities including mining, urbanization, agricultural and industrial activities coupled with high fluxes of nutrients from different areas within the catchment. This situation led to an enhancement of Harmful Algal Blooms (HABs) in the dam reservoir. Phosphorus and Nitrogen are the limiting nutrients for HABs in many eutrophic aquatic systems when their concentrations are raised in such waters. In this study, multi-time-series plot types and scutter plots were analysed to reveal the relationship between HABs proxy chlorophyll-a (Chl-a) and the potential nutrients. Also (Chl-a) data extracted from landsat-8 satellite images were visualised to show the spatial distribution of HABs in the reservoir. The results showed that the Vaal Dam HABs productivity is a function of the total phosphorus (TP) and the organic nitrogen (KJEL_N) levels, which were positively correlated with chlorophyll-a (Chl-a) concentration. The long-term analysis of Chl-a in-situ data (1986 – 2022) measured at one point within the reservoir showed an average of 11.25μg/l but at some stochastic dates, the Chl-a concentration jumped to very high values reaching the maximum value of 452.8μg/l. Such high values are associated with high records of TP and KJEL_N concentrations at the same dates which clearly reveals their effect on the productivity levels. The decadal time series and its trend analysis showed that the average productivity level of Chl-a increased during the studded period from 4.75μg/l in the first decade (1990 – 2000) to 10.51μg/l in the second decade (2000 – 2010) reaching 16.7 during the last decade (2010 – 2020). The increasing averages of the decadal values are associated with the increasing decadal average of its driving factors, TP from 0.1043 to 0.1096 to 0.1119mg/l for the three decades, respectively and KJEL_N from 0.80mg/l in the first decade to 1.14mg/l in the last decade. The decadal average of temperature showed no significant increase, 17.9 °C in the first decade and 18 °C in the last decade which suggests that temperature is not the only enhancing factor of the HABs productivity in the Vaal Dam. The satellite data analysis during the last decade revealed that the HABs spatial dynamics is a function of the dam geometry and the levels of the discharges from its two feeding rivers. Higher concentrations were observed where the reservoir is meandering and within the areas of restricted water circulation.

ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). Approximately 30% of transplants from related donors and up to 50% of transplants from unrelated donors are ABO-incompatible. The immuno-hematologic investigationsmay evaluate donor/recipient ABO mismatch and anti-A/B isohemoagglutinins (IHAs) titration in pre-HSCT phase. Immediate hemolysis or delayed complications (passenger lymphocyte syndrome and pure red cell aplasia) can appear post-HSCT. Some preventive treatmentstake into consideration the manipulation of the product and decision-making algorithms based on the titration of IHAs in the recipient with clinical protocols for the removal/reduction of IHAs through plasma exchange or immunoadsorption procedures. Currently, the best approach in the managementof ABO-incompatibletransplant is not defined in expert consensus documents or with solid evidence. In addition, the methods for IHAs titration are not standardized. The transfusion strategy must consider both the blood group systems of the recipient and the donor until the RBC engraftment and the confirmed ABO conversion (forward and reverse typing) on two consecutive and independent samples. Therefore, ABO incompatibility in the HSCT is an important immuno-hematologic challenge and request all necessary preventive measures including the appropriate selection of ABO blood components for transfusion.

We propose a phenomenological theory of spin behavior in a magnetic field, which explains from the point of view of classical physics the two-valued result of the Stern-Gerlach experiment. The behavior of the spin and intrinsic magnetic moment of an electron wave of an atom in an external magnetic field is considered. We show that in a weak magnetic field, the intrinsic magnetic moment of an electron wave is always oriented parallel to the magnetic field strength vector, while in a strong magnetic field, depending on the initial orientation of the intrinsic magnetic moment, two orientations are realized: either parallel or antiparallel to the magnetic field strength vector. Within the framework of classical electrodynamics, the calculation of the motion of an atomic beam in an inhomogeneous magnetic field is carried out, which reproduces the results of the Stern-Gerlach experiment.

The concept of sustainable management in culture has been recognised in global strategic documents on sustainable development for more than a decade. It is also increasingly reflected in the cultural polices of particular states, and – very importantly –cultural managers responsible for shaping the cultural offer in cities are becoming more interested in this concept. Despite the increasing attention being paid to this topic among both practitioners and theoreticians of management, in none of these documents or other works can we find any content directly related to the possibility of applying this concept in a town which, due to political turmoil, has been divided by a national border. Hence, this gap was the direct impulse for taking up research in this field. In the article, by using different notions of the market, our own definition of a cross-border market for cultural services was developed, and the conditions for the functioning of this market were presented based on the example town of Cieszyn (Poland) and Český Těšín (Czech Republic). In the opinion of the authors of the article, the development and functioning of a cross-border market for cultural services is essential for the application of the concept of sustainable management of the cultural offer in a town divided by a border. For the purpose of the article, a survey and individual interviews with experts shaping the cultural offer in Cieszyn and Český Těšín were conducted. The results of the research prove that despite numerous cross-border Czech-Polish projects carried out by cultural institutions, there are still many barriers in the town which make it difficult for the residents to benefit from the cultural offer available on the other side of the border. These barriers limit the full implementation and application of the concept of sustainable management of the cultural offer.

Terminalia arjuna possesses significant cardio protective, antidiabetic and antioxidant properties as these properties are described in Ayurveda. In the present study, three flavonoids were isolated through the separation and chromatographic purification of the whole plant material of T. arjuna. Spectroscopic characterization identified one of them as a new flavonoid “Terminalone A (1)” and two known flavonoids i.e. 6-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one (2) and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one (3). The bioactivity studies showed considerable antibacterial and antioxidant (DPPH was used as a scavenger) potential for all the three compounds 1-3 where the compound 1 showed strong antibacterial and antioxidant activity.

Tight junctions (TJ) are cell-cell adhesive structures that define the permeability of barrier-forming epithelia and endothelia. In contrast to this seemingly static function, TJs display a surprisingly high molecular complexity and an unexpected dynamic regulation, which allows the TJs to maintain a barrier in the presence of physiological forces and in response to perturbations. Cell-cell adhesion receptors play key roles during the dynamic regulation of TJs. They connect individual cells within cellular sheets and link sites of cell-cell contacts to the underlying actin cytoskeleton. Recent findings support roles of adhesion receptors in transmitting mechanical forces and promoting phase separation. In this review, we discuss newly discovered functions of cell adhesion receptors localized at the TJs and their role in the regulation of the barrier function.

Prior to clinical trials, preclinical testing of oncology drug candidates is performed by evaluating drug candidates with in vitro and in vivo platforms. For in vivo testing, animal models are used to evaluate the toxicity and efficacy of drug candidates. However, animal models often display poor translational results as many drugs that pass preclinical testing fail when tested in humans, with oncology drugs exhibiting especially poor acceptance rates. The FDA Modernization Act 2.0 promotes alternative preclinical testing techniques, presenting the opportunity to use higher complexity in vitro models as an alternative to in vivo testing, including 3D cell culture models. 3D tissue cultures address many of the shortcomings of 2D cultures by more closely replicating the tumour microenvironment through a combination of realistic drug diffusion, paracrine signaling, cellular phenotype, and vascularization that can better mimic native human tissue. This review will discuss the common forms of 3D cell culture, including cell spheroids, organoids, organs-on-a-chip, and 3D bioprinted tissues. Their advantages and limitations will be presented, aiming to discuss the use of these 3D models to accurately represent human tissue and as an alternative to animal testing. The use of 3D culture platforms for preclinical drug development is expected to accelerate as these platforms continue to improve in complexity, reliability, and translational predictivity.

This paper is mainly based on a stricter premise of the twin paradox and the assumption of inertial frame, discusses the properties of time and space under the premise of complete symmetry, and draws an interesting conclusion: the simultaneity of different reference frames is possible realized, and the space is relatively independent. And based on this, the twin paradox, cosmic inflation, ultra-distance action of quantum entanglement, microscopic space motion of particles, measurement problems and other phenomena are tentatively explained from a new angle. This interpretation is exploratory and new. At the same time, the author also proposes an experimental way to test the relative independence of space.At the same time, this paper attempts to strictly prove that Einstein's definition of simultaneity and spatial absoluteness in special relativity may be problematic.

he paper presents an innovative method for tourist route planning inside a destination. The necessity of reorganizing the tourist routes within a destination comes as an immediate response to the Covid-19 crisis. The implementation of the method inside tourist destinations can bring an important advantage in transforming a destination into a safer destination in times of Covid-19 and post-Covid-19. The existing trend of shortening the tourist stay length has been accelerated while the epidemic became a pandemic. Moreover, the wariness for future pandemics has brought into spotlight the issue of overcrowded attractions inside a destination at certain moments. The method presented in this paper proposes a backtracking algorithm, more precisely an adaptation of the travelling salesman problem. The method presented is aimed to facilitate the navigation inside a destination and to revive certain less-visited sightseeing spots inside a destination while facilitating conformation with the social distancing measures imposed for Covid-19 control.

Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks in LMNA-DCM patients are sudden cardiac death and progressive left ventricular ejection fraction deterioration, and therefore most human and animal studies have sought to define the mechanisms through which LMNA mutations provoke cardiac alterations, with particular focus on cardiomyocytes. To investigate if LMNA mutations also cause vascular alterations that might contribute to the etiopathogenesis of LMNA-DCM, we generated and characterized Lmnaflox/floxSM22αCre mice, which constitutively lack lamin A/C in vascular smooth muscle cells (VSMCs), cardiac fibroblasts, and cardiomyocytes. Like mice with whole body or cardiomyocyte-specific lamin A/C ablation, Lmnaflox/floxSM22αCre mice recapitulated the main hallmarks of human LMNA-DCM, including ventricular systolic dysfunction, cardiac conduction defects, cardiac fibrosis, and premature death. These alterations were associated with hyperactivation of Smad3 and elevated expression of the proapoptotic protein caspase 3 in the heart. Lmnaflox/floxSM22αCre mice also exhibited perivascular fibrosis in the coronary arteries, and a switch of aortic VSMCs from the ‘contractile’ to the ‘synthetic’ phenotype. Ex vivo wire myography in isolated aortic rings revealed impaired maximum contraction capacity and an altered response to vasoconstrictor and vasodilator agents in Lmnaflox/floxSM22αCre mice. To our knowledge, our results provide the first evidence of phenotypic alterations in VSMCs that might contribute significantly to the pathophysiology of some forms of LMNA-DCM. Future work addressing the mechanisms underlying vascular defects in LMNA-DCM may open new therapeutic avenues for these diseases.

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) proteins are a diverse and evolutionarily conserved family of cytidine deaminases that provide a variety of functions from tissue-specific gene expression and immunoglobulin diversity to control of viruses and retrotransposons. APOBEC family expansion has been documented among mammalian species, suggesting a powerful selection for their activity. Enzymes with a duplicated zinc-binding domain often have catalytically active and inactive domains, yet both have antiviral function. Although APOBEC antiviral function was discovered through hypermutation of HIV-1 genomes lacking an active Vif protein, much evidence indicates that APOBECs also inhibit virus replication through mechanisms other than mutagenesis. Multiple steps of the viral replication cycle may be affected, although nucleic acid replication is a primary target. Packaging of APOBECs into virions was first noted with HIV-1, yet is not a prerequisite for viral inhibition. APOBEC antagonism may occur in viral producer and recipient cells. Signatures of APOBEC activity include G-to-A and C-to-T mutations in a particular sequence context. The importance of APOBEC activity for viral inhibition is reflected in the identification of numerous viral factors, including Vif, which are dedicated to antagonism of these deaminases. Such viral antagonists often are only partially successful, leading to selection for viral variants.

The contactless coalescence of a droplet is of paramount importance for physical and industrial applications. This paper describes a coalescence method in mid-air via acoustic levitation using an ultrasonic phased array system. Acoustic levitation using ultrasonic phased arrays provides promising lab-on-a-drop applications, such as transportation, coalescence, mixing, separation, evaporation, and extraction in a continuous operation. The mechanism of droplet coalescence in mid-air may be better understood by experimentally and numerically exploring the droplet dynamics immediately before the coalescence. In this study, water droplets were experimentally levitated, transported, and coalesced by controlling acoustic fields. We observed that the edge of droplets deformed and attracted each other immediately before the coalescence. Through image processing, the radii of curvature of the droplets were quantified and the pressure difference between the inside and outside the droplet was simulated to obtain the pressure and velocity information on the droplet surface. The results revealed that the sound pressure acting on the droplet clearly decreased before the impact of the droplets. This pressure on the droplets was quantitatively analyzed from the experimental data. Our experimental and numerical results provide deeper physical insights into contactless droplet manipulation for futuristic lab-on-a-drop applications.

: A strong financialtransaction is an important factor in organizational triumph and sustainability, and it is elucidated in the revised student handbook of the University that can be found on page 96 rules 1 to 5. This study assessed the registered students organizations' profile in terms of its type, registration, years of establishment, functions, and designations of student leaders and advisers. The financial practices or internal control system manages their organizational finances and the problems encountered by the student organizations and eventually proposed a manual of operation for students and youth organization's internal control system. This research used the descriptive design with the aid of questionnaire; data gathering through quota sampling from 57 student leaders and advisers of different student organizations of NEUST. Findings showed that most organizations had their constitution and by-laws but kept only as files and renewal requirements. Some provisions were not known to the officers, mostly were registered more than five years in operation; however, in terms of functions of officers and advisers, the results showed that some functions were not done by the officers who supposed to do it like the auditors who serve as treasurers also, the PRO as the record keeper and the presidents who handled finances and collections and as well as disbursements of funds. Generally, the organizations' financial activities were deemed to be "good", especially budgeting and cash receipt, due to the implementation of "no collection and no tuition fee policy". The researchers concluded that the absence of the proper internal control systems and manual of operation and lack of proper transfer of financial records from the previous sets of officers were the serious problems that should be addressed. Moreover, the student organizations' internal control system could still be improved if there is proper training and supervision in accounting operation.

The primary aim of this study is to investigate the relationship of the Mediterranean diet (MD) with metabolic syndrome (MetS) and its components in Caucasian subjects between 35 and 74 years. The secondary aim is to analyze sex differences. Methods: A cross‑sectional trial. This study utilized data from the EVA, MARK, and EVIDENT studies, a total of 3417 subjects with a mean age of 60.14±9.14 years (57% men). MetS was defined based on the Joint Scientific Statement National Cholesterol Education Program III. Waist circumference, blood pressure, fasting plasma glucose, and lipid profile were measured. Adherence to the MD was assessed with the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire used in the PREDIMED study. Good adherence was considered when the MD value was higher than the median value. Results: The mean value of the MEDAS questionnaire was 5.83±2.04; (Men 5.66±2.06 and women 6.04±1.99; p<0.001). Adherence to the MD was observed by 38.6% (34.3% men and 40.3% women; p<0.001). MetS was observed in 41.6% (39.0% men and 45.2%women p<0.001). In the multiple regression analysis after adjusting for possible confounders, the mean MD value showed a negative association with the number of MetS components per subject (β=-0.336), and with the different components of MetS: Systolic blood pressure (β=-0.011), Diastolic blood pressure (β=-0.029), glycemia (β=-0.009), Triglycerides (β=-0.004), Waist circumference (β=-0.026), except with the HDL-cholesterol value which showed a positive association (β=0.021); (p<0.001 in all cases). The adjusted logistic regression models showed that an increase in MDA decreases the probability of MetS (OR =0.56) and its components: blood pressure ≥130/85 mmHg (OR = 0.63), fasting plasma glucose ≥100 mg/dL (OR = 0.62); triglycerides ≥150 mg/dL (OR = 0.65); waist circumference ≥88 cm in women and ≥102 cm in men (OR = 0.74), and increases high-density lipoprotein cholesterol <40 mg/dL in men or <50 mg/dL in women (OR = 1.70); (p<0.001 in all cases). The results by sex were similar, both in multiple regression and logistic regression. Conclusion: The results of this study suggest that a greater adherence to the Mediterranean diet decreases the probability of presenting Mets globally and by sex.

The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction, and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in a BP-induced mutagenesis in mice. The tested products significantly (p<0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16±9.09 μg/mL, 5.96±1.55 μg/mL and 3.05±0.89 μg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1±63.40 μg/mL and 203.10±17.29 μg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p<0.05) benzo[a]pyrene (BP)-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p<0.05) the BP-induced micronuclei and oxidative damage, together with an increase of glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for adjuvant therapy of cancer.

This study investigates the impact of experienced contact on prejudiced attitudes toward individuals with intellectual disabilities (ID), examining beliefs in a just world (BJW) and social dominance orientation (SDO) as potential serial mediators. Data were collected from 224 university students (M = 23.02, SD = 2.48). Path analysis modeling assessed the structural relationships between the study variables. The findings revealed that experienced contact was negatively and significantly associated with BJW and SDO. Additionally, BJW and SDO fully mediated the relationship between experienced contact and overt prejudice. These findings underscore the influence of individual differences on attitudes toward individuals with ID, establishing a crucial foundation for future research and the development of interventions aimed at reducing prejudice and discrimination.

The investigation of the electromagnetic properties of biological particles in microfluidic platforms may enable wireless monitoring and interaction with functional activity of microorganisms. Of high relevance is the membrane potential as it is one of the most important parameters of living cells. In particular, the complex mechanisms of the cell’s membrane potential are comparable to the dynamics of bacteria membranes, providing a simplified platform for advancing the current techniques and knowledge of general bio-particle dynamics. In this work, we provide a theoretical analysis and experimental results on the microwave detection of bacteria on a microfluidic-based framework for sensing the membrane potential of bacteria. The results enable to further advance the state-of-the-art of electromagnetic bacteria sensing and microfluidic control, and their implication for measuring and interacting with the cell and its membrane potentials, which is of great importance for developing new biotechnological engineered systems and solutions.

We employ hierarchy of models (HoM) with 2, 3 and 4 parameters to reanalyze the nucleation kinetics in the electrodeposition as quantified by n(t) - “the number of nuclei vs. time” data obtained at different overvoltages from precise experiments on electrodeposition of Hg on two different types of Pt-cathodes by Ivan V. Markov and Evgenia Stoycheva [1]. The obtained two scales, nmax and , are used to rescale the original data mapping it on a master curve in coordinates . Our main result is obtained by studying further the dependence of these two scales on the overvoltage (analogue of supersaturation). Surprisingly, for one of the two cathode types - the “hemispherical single-crystal electrode” (as defined by the authors), there is discontinuity in the “ vs. overvoltage” dependence – an almost horizontal jump from 85 to 86 mV accompanied by a change in the slope of the dependence - it is ~ -1 and ~ -0.5 after. For the other cathode - “plane structureless platinum electrode”,  decreases smoothly. Combined, these two behaviors point at the so called “cusp catastrophe”. We compare our findings with published results on protein nucleation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to the cell receptor angiotensin-converting enzyme-2 (ACE2) as the first step in viral cell entry. SARS-CoV-2 spike protein expression in ACE2-expressing cell surface induces cell–cell membrane fusion, thus forming syncytia. To exert its fusiogenic activity, the spike protein is typically processed at a specific site (S1/S2 site) by cellular proteases such as furin. The C488 residue, located at the spike–ACE2 interacting surface, is critical for the fusiogenic and infectious roles of the SARS-CoV-2 spike protein. We further demonstrated that the C488 residue of spike protein is involved in subcellular targeting and S1/S2 processing. C488 mutant spike localization to the Golgi apparatus and cell surface were impaired. Consequently, the S1/S2 processing of the spike protein, probed by anti-Ser-686-cleaved spike antibody, markedly decreased in C488 mutant spike proteins. Moreover, brefeldin A-mediated endoplasmic reticulum-to-Golgi traffic suppression also suppressed spike protein S1/S2 processing. As brefeldin A treatment and C488 mutation inhibited S1/S2 processing and syncytia formation, the C488 residue of spike protein is required for functional spike protein processing.

To demonstrate if botulinum toxin type A (BoNT-A) improves mandibular range of motion and muscle sensibility to palpation in refractory myofascial pain (MFP) patients. METHODS: Eighty consecutive female subjects with refractory MFP, were randomly divided into four equal groups (n=20): BoNT-A low (BoNTA-L/10 U in each temporalis and 30 U in each masseter), BoNT-A medium (BoNTA-M/20 U in each temporalis and 50 U in each masseter), BoNT-A high (BoNTA-H/25 U in each temporalis and 75 U in each masseter) and saline solution 0.9% (SS, placebo control group/0.4 mL in each temporalis and 0.6 mL in each masseter). Clinical measurements of the mandibular movements included: pain-free opening, maximum unassisted and assisted opening, and right and left lateral movements. Palpation tests were performed bilaterally in masseter and temporalis muscle. Results were expressed as median, minimum, maximum, and means ± standard deviation (SD). Chi-Square Test was used to compare differences among groups. A 5% probability level was considered significant in all tests RESULTS: Regardless of dose, all parameters of mandibular range of motion significantly improve after 180 days in BoNT- A groups, when compared to the control group. Pain to palpation on muscles, significantly reduced in all BoNT- A groups regardless of dose, when compared to the control group, after 28 and 180 days of treatment. CONCLUSIONS: Independent of doses, BoNT-A improved mandibular range of motion and muscle sensibility to palpation in refractory MFP patients when compared to SS injections.

Application of chemical pesticides to protect agricultural crops from pests and diseases is discouraged due to their harmful effects on human and environment. Therefore, alternative approaches for crop pro-tection through microbial or microbe originated pesticides have been gaining momentum. Wheat blast is a destructive fungal disease caused by Magnaporthe oryzae Triticum (MoT) pathotype, which poses a seri-ous threat to global food security. Screening of secondary metabolites against MoT revealed that antimy-cin A isolated from a marine Streptomyces sp. had significant inhibitory effect on mycelial growth in vitro. This study aimed to investigate the inhibitory effects of antimycin A on some critical life stages of MoT and evaluate the efficacy of wheat blast disease control by this natural product. Bioassay indicated that antimycin A suppressed mycelial growth, conidiogenesis, germination of conidia and formation of ap-pressoria in germinated conidia of MoT in a dose-dependent manner with minimum inhibitory concen-tration 0.005 μg/disk. If germinated, antimycin A induced abnormal germ tubes (4.8%) and suppressed the formation of appressoria. Interestingly, application of antimycin A significantly suppressed wheat blast disease in both seedling and heading stages of wheat supporting the results from invitro study. This is the first report on inhibition of mycelial growth, conidiogenesis, conidia germination, detrimental morphological alterations in germinated conidia, and suppression of wheat blast disease caused by a Triticum pathotype of M. Oryzae. Further study is required to unravel the precise mode of action of this promising natural compound for considering it as a biopesticide to combat wheat blast.

Patients with lean NAFLD make up an increasing subset of liver diseases. The association between lean NAFLD and feutin-A, which serves as a hepatokine and adipokine, has never been examined. Our study aimed to explore the association of serum fetuin-A among lean and nonlean patients. The study comprised 606 adults from the community, stratified into lean or nonlean (BMI </≥ 24 kg/m2) and NAFLD or non-NAFLD (scoring of ultrasonographic fatty liver indicator, US-FLI ≥ 2/<2). Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD among the tertiles of fetuin-A after adjustment. The least square means were computed by general linear models to estimate marginal means of the serum fetuin-A concentrations in relation to the NAFLD groups. The OR of having NAFLD for the highest versus the lowest tertile of fetuin-A was 2.62 (95% CI: 1.72-3.98; P for trend<0.001). Stratifying by BMI, the OR of having lean NAFLD for the highest versus the lowest tertile of fetuin-A was 2.09 (95% CI: 1.09-3.98; P for trend 0.026), while nonlean NAFLD had no significant association with the fetuin-A gradient after adjustments. Fetuin-A was positively associated with lean NAFLD after adjusting for central obesity and insulin resistance.

Fluorescence-linked immunosorbent assay (FLISA) is a commonly used, quantitative technique for detecting biochemical based on antigen–antibody binding reactions using a well-plate platform. With the developments in the manufacturing technology of microfluidic systems, FLISA can be implemented onto microfluidic disk platforms, which allows the detection of trace biochemical with high resolutions. Apart from requiring a lower proportion of reagent (1/10), this method also reduces the time required for the entire process to less than an hour. The incubation process involves antigen–antibody binding reactions as well as the binding of fluorogenic substrates to target proteins. The protocol for FLISA on a microfluidic platform necessitates the appropriate execution of liquid reagent movements during each step in order to ensure sufficient binding reactions. Herein, we propose a novel microfluidic disk comprising a 3D incubation chamber. Vascular endothelial growth factor as concentration with ng mL-1 is detected sequentially using a benchtop process employing this 3D microfluidic disk. The 3D microfluidic disk is implemented without requiring manual intervention or additional procedures for liquid control. During the incubation process, microbead movement is controlled through centrifugal force, generated due to disk rotation, and gravitational force via bead sedimentation on the sloped floor of the chamber.

Along just over a century of research we moved from learning how to cultivate tissues in a dish to grasping the concepts for creating an entire brain in a vat. As we approach the divisive moment in which we can first detect signs of awareness in such artificially developed organoids, we need to lay foundation for what lays ahead. It is crucial that ethical, legal and moral implications of organoid research are clear and that boundaries are set to separate scientific progress from human life preservation. The largest obstacle may be the definition of consciousness itself, which has arguably been historically neglected by philosophy, psychology and neurosciences at large. One reason may be the difficulties posed by the underlying qualities of awareness, such as its subjective and heterogeneous nature. Another reason may lie on the possibly that consciousness is an overarching emergent property of our brain. For the time being, one can see brain organoids as philosophical zombies, physical analogues of the human brain which mimic sentient human reactions but lack experiential properties of sensation (a.k.a. qualia).

We define degree of dependence of two events A and B in a probability space by using Boltzmann-Shannon entropy function of an appropriate probability distribution produced by these events and depending on one parameter (the probability of intersection of A and B) varying within a closed interval I. The entropy function attains its global maximum when the events A and B are independent. The important particular case of discrete uniform probability space motivates this definition in the following way. The entropy function has a minimum at the left endpoint of I exactly when one of the events and the complement of the other are connected with the relation of inclusion (maximal negative dependence). It has a minimum at the right endpoint of I exactly when one of these events is included in the other (maximal positive dependence). Moreover, the deviation of the entropy from its maximum is equal to average information that carries one of the binary trials defined by A and B with respect to the other. As a consequence, the degree of dependence of A and B can be expressed in terms of information theory and is invariant with respect to the choice of unit of information. Using this formalism, we describe completely the screening tests and their reliability, measure efficacy of a vaccination, the impact of some events from the financial markets to other events, etc. A link is available for downloading an Excel program which calculates the degree of dependence of two events in a sample space with equally likely outcomes.

Cancer stem cells remain a challenge to isolate and characterize because of their plastic phenotype. Using a microfluidic lab-on-a-chip based on ultra-high frequency dielectophoresis, we measured the electromagnetic signature of colorectal cancer cells and demonstrated that cancer stem cells show a distinct and lower electromagnetic signature than differentiated cells. The release of extracellular vesicles from tumor cells can drive tumor progression and metastasis development. As extracellular vesicles from cancer stem cells carry more aggressive content, we treated colorectal cancer cells with these vesicles to test whether the lab-on-a-chip can detect a change in phenotype. The electromagnetic signature of treated cells is modified in comparison to untreated cells and sometimes even when no biological change is observed. The lab-on-a-chip provides rapid and relevant result without prior labeling compared to conventional biological approaches. It could be useful in the clinic for early detection of cancer stem cells in the tumor mass and for monitoring the aggressive potential of extracellular vesicles in the bloodstream in order to adapt therapeutic management and prevent relapse.

The reference method for cefiderocol antimicrobial susceptibility testing is broth microdilution (BMD) with iron-depleted-Mueller-Hinton (ID-MH) medium, whereas breakpoints recommended for disk diffusion (DD) are based on MH-agar plates. We aimed to compare the performance of the commercial BMD tests ComASP (Liofilchem) and UMIC (Bruker), DD and E-test using MH- and ID-MH-agar plates with the reference BMD method using 100 carbapenem-resistant-A. baumannii isolates. Standard BMD was performed according to the EUCAST guidelines, DD and E-test were carried out using two commercial MH-agar plates (bioMérieux and Liofilchem) and an in-house ID-MH-agar plate, while ComASP and UMIC were performed according to the manufacturer’s guidelines. DD performed with the ID-MH-agar plates led to a higher categorical agreement (CA, 95.1%) with standard BMD and fewer categorization errors compared to the commercial MH-agar plates (CA bioMérieux 91.1%, Liofilchem 89.2%). E-test on ID-MH-agar plates exhibited a significantly higher essential agreement (EA, 75%) with standard BMD compared to the two MH-agar plates (EA bioMérieux 57%, Liofilchem 44%), and showed a higher performance in detecting high-level resistance than ComASP and UMIC (mean log2 difference with standard BMD for resistant isolates of 0.5, 2.83 and 2.08, respectively). In conclusion, DD and E-test on ID-MH-agar plates exhibit a higher diagnostic performance than on MH-agar plates and the commercial BMD methods. Therefore, we recommend using ID-MH-agar plates for cefiderocol susceptibility testing of A. baumannii.

The article analyzes the problems connected with ensuring the coordinated operation of slipway drives that arise during the launch of a ship. The dynamic model of load of the electric drive of the ship's cart is obtained taking into account the peculiarities of the construction of the ship-lifting complex, which allows to analyze the influence of external factors and random influences during the entire process of launching the ship. A linearized mathematical model of the dynamics of a complex vessel movement in the process of descent in the space of states is developed, which allows to identify the mode of operation of the multi-drive system, taking into account its structure. The analysis of efficiency of application of recurrent methods of identification (stochastic approximation and least squares) of the parameters of the linearized model in the space of states is carried out. A decision support system has been developed in the automated system of operational control by the module for estimating the situation and the control synthesis to ensure a coherent motion of a complex ship-carts object in a two-phase environment.

Balínt Syndrome is an acquired disorder manifesting in the inability to recognize several objects at once (simultagnosia), inaccurate visually guided limb movements despite intact motor function (optic ataxia) and the inability to make accurate voluntary saccades to visual targets despite demonstrating unrestricted range of eye movements (ocular motor apraxia). Here we report the first case of a patient presenting with Balínt Syndrome caused by a platelet-derived growth factor receptor A mutation (PDGFRA)-induced Hypereosinophilic Syndrome (HES).

Bisphenol A is a remarkable chemical compound for its many applications mainly in the plastics industry, but also for its toxic effects on the environment and human health. BPA (4,4-isopropylidenediphenol) is an anthropogenic compound, moderately soluble in water (120 – 300 mg/l) at room temperature, and highly soluble in alkaline solutions, ethanol and acetone. BPA can bioconcentrate, bioaccumulate and biomagnify through food webs until it reaches humans. To prevent this, effective strategies are sought to allow its removal from the environment, through physico-chemical or enzymatic methods, advanced oxidation, adsorption and biodegradation, ultrasonic degradation. This article shows a comparative study regarding adsorption of BPA on Active carbon and zeolitic tuff, ZTC. In this paper, the characterization of the zeolitic tuff Rupea adsorbent, was carried out from an elemental and mineralogical point of view, pore size and elemental distribution, using SEM, EDAX, and XRD analysis. The pore size varies from 30 nm to 10 µm, atomic ratio Si/Al≥4, and the 80 % of mineralogical composition represent Ca Clinoptilolite zeolites Ca Clinoptilolite zeolite ((Na1.32K1.28Ca1.72Mg0.52)(Al6.77Si29.23O72)(H2O)26.84). Also, a comparative study of the adsorbtion capacity of bisphenol A from synthetic solutions on activated carbon type - Norit GAC 830 W, GAC, as well as on Clinoptilolite-type zeolitic tuff, ZTC, Rupea, was carried out. The experiments were carried out at a temperature of 20 ºC, a pH of 4.11; 6.98 and 8.12, and ionic strength being assured using KCl of 0.01 M, and 0.1 M. The adsorption capacities of GAC and ZTC tend to 115 mg/g and 50 mg/g respectively, at 8.12 pH and ionic strength of 0 M. The Langmuir mathematical model most faithfully describes the adsorption equilibrium of BPA. The maximum adsorption capacity for both adsorbents increases with increasing pH, and decreases with increasing ionic strength.

Methionine 77 in calmodulin can be stereospecifically oxidized to methionine sulfoxide by mammalian methionine sulfoxide reductase A. Whether this has in vivo significance is unknown. We therefore created a mutant mouse in which wild-type calmodulin-1 was replaced by a calmodulin containing a mimic of methionine sulfoxide at residue 77. Total calmodulin levels were unchanged in the homozygous M77Q mutant, which is viable and fertile. No differences were observed on learning tests, including the Morris water maze and associative learning. Cardiac stress test results were also the same for mutant and wild type mice. .However, young male and female mice were 20% smaller than wild type mice, although food intake was normal for their weight. Young M77Q mice were notably more active and exploratory than wild type mice. This behavior difference was objectively documented on the treadmill and open field tests. The mutant mice ran 20% longer on the treadmill than controls, and in the open field test, the mutant mice explored more than controls and exhibited reduced anxiety These phenotypic differences bore a similarity to those observed in mice lacking calcium/calmodulin kinase Iiα (CaMKIIα). We then showed that M77Q calmodulin was less effective in activating CaMKIIα than wild type calmodulin. Thus, characterization of the phenotype of a mouse expressing a constitutively active mimic of calmodulin led to the identification of the first calmodulin target that can be differentially regulated by the oxidation state of Met77. We conclude that reversible oxidation of methionine 77 in calmodulin by MSRA can regulate cellular function.

Control as a Service (CaaS) is an emerging paradigm where low-level control of a device is moved from a local controller to the Cloud, and provided to the device as an on-demand service. Among its many benefits, CaaS gives the device access to advanced control algorithms which may not be executable on a local controller due to computational limitations. As a step toward 3D printer CaaS, this paper demonstrates the control of a 3D printer by streaming low-level stepper motor commands (as opposed to high-level G-codes) directly from the Cloud to the printer. The printer is located at the University of Michigan, Ann Arbor, while its stepper motor commands are calculated using an advanced motion control algorithm running on Google Cloud computers in South Carolina and Australia. The stepper motor commands are sent over the Internet using the user datagram protocol (UDP) and buffered to mitigate transmission delays; checks are included to ensure accuracy and completeness of the transmitted data. All but one part printed using the cloud-based controller in both locations were hitch free (i.e., no pauses due to excessive transmission delays). Moreover, using the cloud-based controller, the parts printed up to 54% faster than using a standard local controller, without loss of accuracy.

Polycyclic aromatic hydrocarbons (PAHs), which consist of low-molecular-weight PAHs (LMW-PAHs) and high-molecular-weight PAHs (HMW-PAHs), form an important class of pollutants. Pyrene and benzo[a]pyrene (BaP) are the main pollutants belonging to HMW-PAHs, and their degradation by microorganisms remains an important strategy for their removal from the environments. Extensive studies have been carried out on the isolation and characterisation of microorganisms that actively degrade LMW-PAHs, and to a certain extent, the HMW-PAH pyrene. However, so far, limited work has been carried out on BaP biodegradation. BaP consists of five fused aromatic rings, which confers this compound a high stability, rendering it less amenable to biodegradation. The current review summarizes the emerging reports on BaP biodegradation. More specifically, work carried out on BaP bacterial degradation and current knowledge gaps that limit our understanding of BaP degradation are highlighted. Moreover, new avenues of research on BaP degradation are proposed, specifically in the context of the development of “omics” approaches

Colorectal cancer is the third most common disease and the second most common cause of death in the world. The drug for second-line treatment depends on the drugs used in first-line treatment and biomarker status. As biomarkers, the RAS gene, BRAF gene, and dMMR/MSI-H, TMB-H, and HER2 statuses have been established in clinical practice, and the corresponding molecularly targeted therapeutic agents are selected based on biomarker status. Given the frequency of biomarkers, it is assumed that when patients move on to second-line treatment, an angiogenesis inhibitor is selected in many cases. For second-line treatment, three angiogenesis inhibitors, bevacizumab (BEV), ramucirumab (RAM), and aflibercept (AFL), are available, and one of them is combined with cytotoxic agents. These three angiogenesis inhibitors are known to inhibit angiogenesis through different mechanisms of action. Although no useful biomarkers are established for selecting angiogenesis inhibitors, previous biomarker studies have suggested that angiogenesis-related factors such as VEGF-A and VEGF-D might be predictors of therapeutic efficacy of angiogenesis inhibitors. These biomarkers are measured as protein levels in plasma and are considered to be hopeful biomarkers. We consider that the rationale for selecting among these three angiogenesis inhibitors should be clarified to benefit patients.

In the study of rough sets, there are many covering approximation spaces, how to classify covering approximation spaces has become a hot issue. In this paper, we propose concepts covering approximation $T_{1}$-space, $F-$symmtry, covering rough continuous mapping, covering rough homeomorphism mapping to solve this question. We also propose a new method for constructing topology in Theorem 5.1, and get the following properties: (1) For each $x\in U$, $\{X_{i}:i\in I\}\subseteq \mathcal{P}(U)$ is all the subsets of $U$ which contains $x$ and $*$ is a reflexive relation on $U$. If $V\in \tau$ is a subset of $U$ and $x\in V$, then $\underline{*}(\bigcap \limits_{i\in I}X_{i})$ is the smallest subset of $U$ and $x \in \underline{*}(\bigcap \limits_{i\in I}X_{i})\subseteq V$. Denoted by $C(x)=\bigcap \{\underline{*}(X_{i}):x\in \underline{*}(X_{i}),i\in I\}$. (2)If $V\in \tau$ is a subset of $U$, then $V =$ $\bigcup \limits_{x\in V} C(x)$. (3) Let $\{\underline{*}(X_{i}):x\notin \underline{*}(X_{i}), i\in I\}$, then $\overline{\{x\}}$ $=$ $U \setminus \bigcup \limits_{x\notin \underline{*}(X_{i}), i\in I}\underline{*}(X_{i})$; (4) Let $*$ be a reflexive relation on $U$. For every $X\subseteq U$, we have $int(\underline{*}(X))=\underline{*}(X)$. Where $int(\underline{*}(X))$ represents the interior of $\underline{*}(X)$. (5) Let $\{\underline{*}(X_{i}):x\in \underline{*}(X_{i}),i\in I\}$ be a family subsets of $U$, then $\{\underline{*}(X_{i}):x\in \underline{*}(X_{i}),i\in I\}$ is a base for $(U,\tau)$ at the point $x$. \\

When it is in the template RNA, the naturally occurring m¹A epitranscriptomic RNA modification was recently reported to be able to stop the RNA polymerization reaction catalyzed by the RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. In this report, we report that m¹A via its triphosphate form (m¹ATP) can be incorporated into RNA by the same RdRp. These two findings point a new direction for antiviral drug development based on m¹A for combatting COVID-19. More broadly, it is possible that the large pool of epigenetic RNA as well as DNA modifications could serve as a treasury for drug discovery aimed at combating various infectious and other diseases.

Alzheimer’s and Parkinson's diseases (AD and PD) are amongst top of the prevalent neurodegenerative disease. One-third of PD patients are diagnosed with dementia, a pre-symptom of AD, but the underlying mechanism is elusive. Amyloid beta (Aβ) and α-synuclein are two of the most investigated proteins, whose pathological aggregation and spreading are crucial to the pathogenesis of AD and PD, respectively. Transcriptomic studies of the mammalian central nervous system shed light on gene expression profiles at molecular levels, regarding the complexity of neuronal morphologies and electrophysiological inputs/outputs. In the last decade, the booming of the single-cell RNA sequencing technique helped to understand gene expression patterns, alternative splicing, novel transcripts, and signal pathways in the nervous system at single-cell levels, providing insight for molecular taxonomy and mechanistic targets of the degenerative nervous system. Here, we re-visited the cell-cell transmission mechanisms of Aβ and α-synuclein in medi-ating disease propagation, and summarized recent single-cell transcriptome sequencing from different perspectives and discussed its understanding of neurodegenerative diseases.

Objective To analyze the influence of HIV in penitentiary institutions through an exhaustive lexiconmetric and sentiment analysis of news in the Spanish written press related to HIV and prison. Material an method observational, descriptive, and retrospective design based on news published in Spanish newspapers from 1981 to 2020, linking HIV infection with penitentiary institutions. Natural language processing and lexiconmetry techniques were used, using the Python programming language and ATLAS Ti v.9 software. Result: 318 articles were analyzed, with 10,502 distinct words. The sentiment of news was evaluated in three different periods: the discovery of HIV, and the periods before and after the existence of antiretroviral treatments. N-gram analysis and word cloud creation were carried out for each period. In the initial phase, ignorance predominated, and prominent terms such as "homosexual," "isolate," "test," "trial," or "confirm" were observed. In the period before antiretroviral treatments, news reflected negative feelings and criticism of prison policy, with keywords such as "give birth," "drug," "carrier," or "disease." With the arrival of treatments, news showed an evolution towards a more positive tone, highlighting terms such as "treatment," "release," or "syringes”.Conclusions: The presence of HIV in Spanish prisons has experienced a significant evolution from an alarming situation to an improvement in the care of inmates, driven by institutional adaptation and advances in antiretroviral treatments.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered a recent pandemic of respiratory disease and affected almost every country all over the world. A large amount of natural bioactive compounds is under clinical investigation for various diseas-es. Especially, marine natural compounds are gaining more attention in the new drug develop-ment process. The present study has aimed to identify potential marine-derived inhibitors against the target proteins of COVID-19 using a computational approach. Currently, 16 marine clinical-level compounds were selected for computational screening against the four SARS-CoV-2 main proteases. Computational screening resulted from the best drug candidates for each target based on the binding affinity scores and amino acid interactions. Among these, five marine-derived compounds namely Chrysophaentin A (-6.6 kcal/mol), Geodisterol sulfates (-6.6 kcal/mol), Hymenidin (-6.4 kcal/mol), Plinabulin (-6.4 kcal/mol) and Tetrodotoxin (-6.3 kcal/mol) expressed the minimized binding energy and molecular interactions such as covalent and hydrophobic interactions to the SARS CoV-2 Main Protease. Using Molecular dynamic stud-ies, the Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), Radius of Gyration (ROG), and Hydrogen bonds (H-Bonds) values were calculated for SARS-CoV-2 Main Protease with Hymenidin docked complex. Additionally, in silico Druglikeness and pharmaco-kinetic property assessments of the compounds demonstrated favorable druggability. These re-sults suggested that marine natural compounds are capable of fighting SARS-CoV-2. Further, in vitro and in vivo studies need to be carried out to confirm their inhibitory potential.

Vascular endothelial growth factors (VEGFs) are regarded as the key vasculogenic mediators in the human body, of which VEGF-A is considered as one of the important types. It is the major growth factor possessing increasing vascular permeability as well as angiogenesis properties. This article provides intuition into the different effects of VEGF-A on vessels in ovarian hyper stimulation syndrome (OHSS) which is defined as a complication of in-vitro fertilization for infertility treatment, and obesity, a universally health problem. These are two dissimilar pathways outcomes for VEGF-A effects, thereby This article reviews updated information about the mentioned disorders and reveals that how this kind of growth factor yields different results on vasculature by activating distinct intracellular signaling in endothelial cells.

In this paper, impulsive control on a single-species Markovian jumping ecosystem leads to a stability criterion, and the newly-obtained theorems improve the related existing results. Numerical examples illuminate the effectiveness.

This study explores the use of Bayesian Neural Networks (BNNs) for estimating chlorophyll-a concentration ([CHL-a]) from remotely sensed data. The BNN model enables uncertainty quantification, offering additional layers of information compared to traditional ocean colour models. An extensive in situ bio-optical dataset is utilized, generated by merging 27 data sources across the world’s oceans. The BNN model demonstrates remarkable capability in capturing mesoscale features and ocean circulation patterns, providing comprehensive insights into spatial and temporal variations in [CHL-a] across diverse marine ecosystems. In comparison to established ocean colour algorithms, such as Ocean Colour 4 (OC4), the BNN shows comparable performance in terms of correlation coefficients, errors, and biases when compared with the in situ data. The BNN, however, further provides critical information about the distribution of [CHL-a], which can be used to assess uncertainties in the prediction. Moreover, the BNN model’s ability to provide more information for coastal waters, especially with higher spatial resolution imagery, offers valuable advantages for marine research and management. By quantifying uncertainty, the model builds confidence in [CHL-a] predictions, even in regions with limited data coverage. This is reflected by the spread in the model predictions, where the BNN can detect a range of uncertainty bounds that reflect confidence in the retrievals. Introducing BNNs as probabilistic ocean colour models represents a significant advancement, enabling more accurate and reliable predictions of [CHL-a] in the global oceans.

Insect behavior is coordinated mainly by smell, through the diverse odor-binding proteins (OBP) that allow them to identify and recognize their environment. Sensory information collected through smell is then analyzed and interpreted in the brain, allowing for correct insect functioning. The behavior of honey bees (Apis mellifera L.) can be affected by different pathogens, such as deformed wing virus (DWV). In particular, DWV variant A (DWV-A) is capable of altering olfactory sensitivity, reducing the gene expression of different OBPs, including those associated with nursing behavior. DWV is also capable of replicating itself in the sensory lobes of the brain, further compromising the processing of sensory information. This study evaluated the behavioral response of nurse honey bees exposed to a pheromone compound and the alterations in the gene expression of pre- and post-synaptic neuronal genes neuroxins-1 and neurogilin-1 in the bee heads and OBP proteins in antennae of nurse bees inoculated with DWV-A. The behavioral response of nurse bees exposed to the larval pheromone compounds benzyl alcohol was analyzed using a Y-tube olfactometer. The viral load, gene expression of OBP5 and OBP11 in antennae and the neuroxins-1 and neurogilin-1 in the bee heads were analyzed by qPCR. High viral loads significantly reduced the ability of 10- and 15-day-old nurse honey bees to choose the correct pheromone compound. Also, the gene expression of OBP5, OBP11, neuroxin-1 and neurogilin-1 in nurse honey bees decreased when they were highly infected with DWV-A. These results suggest that a DWV-A infection can disturb information processing and cause nurse honey bees to reduce their activity inside the hive, altering internal cohesion.

This study aims to develop and implement a methodology for retrieving bio-optical parameters in a lagoon located in the Biobío region, in south-central Chile by analyzing time series of Landsat-8 satellite images, specifically using the multispectral OLI sensor. The bio-optical parameters, i.e., chlorophyll-a (mg·m^-3) and turbidity (NTU) were also measured in-situ synchronized with the satellite passes to minimize the impact of atmospheric distortions. To calibrate the satellite images, various atmospheric correction methods (including ACOLITE, C2RCC, iCOR, and LaSRC) were evaluated during the image preprocessing phase. Spectral signatures obtained from the scenes for each atmospheric correction method were then compared with spectral signatures acquired in-situ on the water surface. In short, the ACOLITE model emerged as the best fit for the calibration process. Subsequently, we harnessed the reflectance data derived from the ACOLITE model to establish correlations between various spectral indices and the in-situ data. The empirical retrieval models (based on band combinations) that showed superior performance, as indicated by higher R² values, were subjected to rigorous statistical validation and optimization by applying a bootstrapping approach. Our analysis covered a spectrum of dates, seasons, and years, which allowed us to search deeper into the evolution of the trophic state associated with the lake. We identified a striking eight-year period (2014-2022) characterized by a decline in chlorophyll-a concentration in the lake possibly attributable to governmental measures in the region for the protection and conservation of the lake. The results of this initial study serve as the basis for the creation of a modern monitoring system that enhances traditional point-based methods, offering a holistic view of the ongoing processes within the lake.

Aberrant estrogen receptor (ER) signaling is a major driver of breast tumor growth and progression. Sigma 2 receptor has long been implicated in breast carcinogenesis based on pharmacological studies, but its molecular identity had been elusive until TMEM97 was identified as the receptor. Herein we report that TMEM97/sigma 2 receptor is highly expressed in ER positive breast tumors and its expression is strongly correlated with ER and progesterone receptor (PR) but not with HER2 status. High expression levels of TMEM97 are associated with reduced overall survival of patients. Breast cancer cells with increased expression of TMEM97 had growth advantage over the control cells under both nutrition limiting and sufficient conditions, while knockdown of TMEM97 expression reduced tumor cell proliferations. When compared to their vector control cells, MCF7 and T47D cells with increased TMEM97 expression presented increased resistance to tamoxifen treatment and also grew better under estrogen depleted conditions. TMEM97/sigma 2 receptor enhanced ERα transcriptional activities and increased the level of transactivated ERα, especially the nuclear soluble and chromatin bounded ERα. Increased TMEM97 also stimulated mTOR/S6K1 signaling pathways in MCF7 and T47D cells. The increased level of active, phosphorylated ERα, and the enhanced resistance to tamoxifen treatment with increased TMEM97 could be blocked by an mTOR inhibitor. Knockdown of TMEM97 expression reduced ERα and mTOR/S6K1 signaling activities, rendering the cells with increased sensitivity to tamoxifen. The observations suggest that TMEM97/sigma 2 receptor is a novel regulator of ERα activities in breast tumor cell growth.

In this review paper, the occurrence in the plant kingdom and the biological activities associated to two specific phenyl-ethanoid glycosides i.e., leucosceptoside A and leucosceptoside B, were shown and discussed. This is the first work ever done on such subject. Analysis of the literature data clearly indicates that leucosceptoside A is much more common in plants and exerts many more biological activities than leucosceptoside B even if this also presents some important elements. All of this was widely discussed in this paper.

Despite a large amount of data on the association of folate metabolism disturbances with different aspects of schizophrenia, the role of the MTHFD1 1958 G>A polymorphism in this disorder is barely studied. The aim of this study was to assess the distribution of alleles and genotypes frequencies of MTHFD1 1958 G>A in patients with schizophrenia and healthy controls and to study the association of allele/genotype carriage of this SNP with biochemical markers of one-carbon metabolism and with the severity of schizophrenia symptoms. Methods: In 57 patients with schizophrenia and 37 healthy volunteers the carriage of alleles/genotypes of the MTHFD1 1958 G>A and biochemical markers of folate metabolism disturbances were evaluated. Clinical symptoms of schizophrenia and the severity of extrapyramidal side effects of therapy were assessed in patients. Results: an association of the wild GG genotype with schizophrenia was shown (GG versus AG / AA: χ2 = 7.31; p = 0.007). The serum folate level in carriers of the wild genotype GG is lower (in all participants p = 0.024, in patients p = 0.10), and the level of cobalamin in this subgroup is higher (in all participants p = 0.047, in patients p = 0.091) than in carriers of other genotypes. Patients carrying the G allele had less severe negative symptoms (p = 0.0041) and extrapyramidal side effects of antipsychotics (p = 0.054), than patients with AA genotype. The age of psychosis manifestation is the later, the more wild alleles G are present in the genotype (p = 0.00195).

This review aimed to update the main aspects of aflatoxin production, occurrence and incidence in selected countries, and associated aflatoxicosis outbreaks. Means to reduce aflatoxin incidence in crops were also presented with an emphasis on the environment-friendly technology using atoxigenic strains of Aspergillus flavus. Aflatoxins are unavoidable widespread natural contaminants of foods and feeds with serious impact on health, agricultural and livestock productivity, and food safety. They are secondary metabolites produced by Aspergillus species distributed on three main sections of the genus (section Flavi, section Ochraceorosei, and section Nidulantes). Poor economic status of a country exacerbates the risk and the extent of crop contamination due to faulty storage conditions that are usually suitable for mold growth and mycotoxin production: temperature of 22 to 29°C and water activity of 0.90 to 0.99. This situation paralleled the prevalence of high liver cancer and the occasional acute aflatoxicosis episodes that have been associated with these regions. Risk assessment studies revealed that Southeast Asian and Sub-Saharan African countries remain at high risk and that, apart from the regulatory standards revision to be more restrictive, other actions to prevent or decontaminate crops are to be taken for adequate public health protection. Indeed, a review of publications on the incidence of aflatoxins in selected foods and feeds from countries whose crops are classically known for their highest contamination with aflatoxins, reveals that despite the intensive efforts made to reduce such an incidence, there has been no clear tendency, with the possible exception of South Africa, towards sustained improvements. Nonetheless, a global risk assessment of the new situation regarding crop contamination with aflatoxins by international organizations with the required expertise is suggested to appraise where we stand presently.

Vitamin A and E are important during pregnancy, the neonatal period, and childhood. The objective of this study was to assess whether maternal RRR-a-tocopherol supplementation affects serum and breast milk retinol. Serum was collected at baseline and twenty days later, and breast milk, at baseline, and on days 1, 7, and 20 after delivery. After the baseline serum collection, the supplemented group (n=16) received a single 400 IU of RRR-α-tocopherol. The control group (n=18) was only performed collections. Retinol and alpha tocopherol levels were determined by liquid chromatography. Serum retinol and alpha tocopherol at baseline and 20 days after delivery indicated proper vitamin A (> 20 µg/dL) and E (> 516 μg/dL) statuses in the control and supplemented groups (p > 0.05). Colostrum retinol levels on days 1 and 7 after delivery were significantly higher in the supplemented group (p = 0.018 and p = 0.012, respectively). Maternal vitamin E supplementation increased colostrum retinol by 52.23% and 111.2%, 24 hours and 7 days, respectively. However, retinol in mature milk did not differ between the groups (p > 0.05). In conclusion, the supplementation with 400 IU of RRR-α-tocopherol improved vitamin A bioavailability in breast milk.

Morphine-induced antinociception is partially reduced in interleukin-31 (IL-31) receptor A (IL-31RA)-deficient mice, indicating that IL-31RA is crucial for morphine-induced peripheral antinociception. Herein, we examined the combined effects of IL-31 and morphine on antinociceptive activity and itch-associated scratching behavior (LLS) in mice, and elucidated the regulatory mechanisms. A hot-plate test was used to assess antinociception. LLS was automatically detected and recorded via computer. IL-31RA mRNA expression was assessed using real-time polymerase chain reaction. Repeated pre-treatment with IL-31 resulted in significant antinociceptive activity. Repeated administration of morphine decreased the morphine-induced antinociceptive activity, LLS counts, and regular dose, and inhibited IL-31-induced LLS. These results suggested that repeated administration of morphine depleted inter-neuronal IL-31RA levels, preventing morphine-induced antinociception. Therefore, IL-31 may be helpful as an adjunct analgesic to morphine. To explore the benefits of IL-31, its influence on morphine-induced antinociceptive tolerance in mice was examined. IL-31 and morphine combination increased analgesic action which increased the expression of DRG neuronal IL-31RA, elucidating the site of peripheral antinociception of morphine. This site may induce exocytosis of IL-31RA in the sensory nervous system. Collectively, the suppressive effect of IL-31 on morphine-induced antinociceptive tolerance may result from IL-31RA supplementation in sensory nerves.

The nitrogen-doped amorphous oxide semiconductor (AOS) thin film transistors (TFTs) with double-stacked channel layers (DSCL) were prepared and characterized. The DSCL structure composed of nitrogen-doped amorphous InGaZnO and InZnO films (a-IGZO:N/a-IZO:N or a-IZO:N/a-IGZO:N) made the corresponding TFT devices exhibit quite large field-effect mobility due to the existence of double conduction channels. Especially, the a-IZO:N/a-IGZO:N TFTs showed even better electrical performance (μ_FE = 15.0 cm²·V^-1·s^-1, SS = 0.5 V/dec, V_TH = 1.5 V, I_ON/I_OFF = 1.1×10⁸) and stability (V_TH shift of 1.5, -0.5, and -2.5 V for positive bias-stress, negative bias-stress and thermal stress tests, respectively) than the a-IGZO:N/a-IZO:N TFTs. Based on the X-ray photoemission spectroscopy measurements and energy band analysis, it was assumed that the optimized interface trap states, the less ambient gas adsorption, and the better suppression of oxygen vacancies in the a-IZO:N/a-IGZO:N hetero-structures might be responsible for the better behaviors of the corresponding TFTs.

Historically, viral hepatitis is a considerable public health problem in Central Asian countries, which may have worsened after dissolution of the Soviet Union. However, up-to-date seroepidemiological studies are lacking. The aim of the present study was, therefore, to provide current estimates of seroprevalence of viral hepatitis in Kyrgyzstan, one of the economically least developed countries in the region. We conducted a population-based cross-sectional study in 2018 in the capital of Kyrgyzstan, Bishkek (n=1075). Participants, children and adults, were recruited from an outpatient clinic. Data were collected during face-to-face interviews. A blood sample (6 ml) was collected from each participant and tested with ELISA for the presence of serological markers for five viral hepatitides (A, B, C, D and E). Poststratification weighting was performed to obtain nationally representative findings. The overwhelming majority of the study participants were positive for anti-HAV (estimated seroprevalence, 75.3%; 95% confidence interval: 72.5–77.9%). The weighted seroprevalence estimates of HBsAg, anti-HCV and anti-HDV were 2.2% (1.5–3.3%), 3.8% (2.8–5.1%), and 0.40% (0.15–1.01%), respectively. Anti-HEV seropositivity was 3.3% (2.4–4.5%). Of the 33 HBsAg positive participants, five (15%) were anti-HDV positive. Our study confirms that Kyrgyzstan remains a high endemic country for hepatitis virus A and C infections. However, seroprevalences of HBV and HDV were lower than previously reported, and based on these data, the country could potentially be reclassified from high to (lower) intermediate endemicity. The observed anti-HEV seroprevalence resembles the low endemicity pattern characteristic of high-income countries.

The study within the current research is focused on theoretical assessment of sustainable aviation fuels (SAF) obtained by blending traditional jet fuels Jet A and different liquids (biodiesel and alcohols) from analytical point of view. Within this paper in-depth analysis ofthe physical-chemical properties of Jet A fuel blended with different biodiesels and alcohols has been performed. Also within the blends Aeroshell 500 oil has been added (5% vol.) for ensuring the lubrication of the turbo engine. The blends consists of: Jet Aaviation fuel + biodieselfrom: palm oil, pork fat, sunflower oil and alcohols: methanol, ethanol and butanol. All the 6 liquids have been blended with Jet A in the following percentages: 10, 20 and 30%. Flash point, kinematic viscosity, density, freezing point, elemental analysis and FTIR analysis have been performed for all the liquids: Aeroshell 500, jet A, jet A + 10, 20, 30% biodiesel from waste palm oil, pork fat and waste sunflower oil, jet A + 10, 20, 30% methanol, ethanol and butanol, biodiesels and alcohols. The obtained results shows the influence of each of the blend’s components on the physical-chemical properties of the blends. Based on the physical-chemical analysis of the blends, conclusions on the behavior of the blends during burning and the gaseous pollutants resulting from the burning process can be drawn.

The purpose of this study was to evaluate the bioactivity and cell response of a well-characterized Nurse´s A-phase (7CaO•P2O5•2SiO2) ceramic and his effect compared to a control (tissue culture polystyrene-TCPS) on the adhesion, viability, proliferation and osteogenic differentiation of ahMSCs in vitro. Cell proliferation (Alamar Blue Assay), Alizarin Red-S (AR-s) staining, alkaline phosphatase (ALP) activity, osteocalcin (OCN) and collagen I (Col I) were evaluated. Also, field emission scanning electron microscopy (FESEM) images were acquired in order to visualise the cells and the topography of the material. The proliferation of cells growing in a direct contact with the material was slower at early stages of the study because of the new environmental conditions. However, the entire surface was colonized after 28 days of culture in growth medium (GM). Osteoblastic differentiation markers were significantly enhanced in cells growing on Nurse´s A phase ceramic and cultured with osteogenic medium (OM), probably due to the role of silica to stimulate the differentiation of ahMSCs. Moreover, calcium nodules were formed under the influence of ceramic material. Therefore, it is predicted that Nurse´s A-phase ceramic would present high biocompatibility and osteoinductive properties being a good candidate to be used as a biomaterial for bone tissue engineering.

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here we studied the effect of 12 weeks drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males with slightly higher adipocyte area values in both males and females under clozapine medication. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine medication. IR-ß expression changed sex-specifically in the clozapine medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-medicated females. Taken together, clozapine and haloperidol have a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined and probably in their effect on liver metabolism.

Obesity and overweight are associated with many metabolic diseases, such as hypertension, diabetes, and dyslipidemia, which are closely related to a sedentary lifestyle and lack of exercise. Aerobic exercise effectively increases the high-density lipoproteins-cholesterol (HDL-C) levels and decreases the triglyceride (TG) levels. The consumption of Cuban policosanol (Raydel®) is also effective in enhancing the HDL-C quantity and HDL functionality to treat dyslipidemia and hypertension. On the other hand, no study has examined the effects of a combination of high-intensity exercise and policosanol consumption in obese subjects to improve metabolic disorders. In the current study, 17 obese subjects (average BMI 30.0±1.1 kg/m2, eight male and nine female) were recruited to participate in a program combining exercise and policosanol (20 mg) consumption for 12 weeks. After completion, their BMI, waist circumference, total fat mass, systolic blood pressure (SBP), and diastolic blood pressure (DBP) decreased by approximately 15% (p=0.022), 12.7% (p=0.008), 33% (p=0.006), 11% (p<0.046), and 13% (p=0.007), respectively. In the serum lipid profile, at week 12, they showed a remarkable decrease in the total cholesterol (TC) and triglyceride (TG) levels, up to 17% (p<0.019) and 54% (p<0.002) from the baseline, respectively. Although the serum HDL-C was increased by approximately +12% from the baseline, the percentage of HDL-C in TC, HDL-C/TC (%), was increased by up to +32% (p=0.007) at week 12. The serum coenzyme Q10 (CoQ10) level was increased 1.2-fold in all participants at week 12 from the baseline. In particular, the male participants showed a 1.4-fold increase (p=0.027) from the baseline. The larger increase in serum CoQ10 was correlated with the larger increase in the serum HDL-C during 12 weeks. The hepatic function parameters were improved; the serum -glutamyl transferase decreased at week 12 by up to 55% (p<0.007), while the aspartate aminotransferase and alanine transaminase levels decreased within the normal range. In the lipoprotein level, the extent of oxidation and glycation were reduced significantly in VLDL and LDL, with a remarkable decrease in the TG content in particles. The antioxidant abilities of HDL2 and HDL3, such as paraoxonase (PON) and ferric ion reduction ability (FRA), were enhanced significantly by up to 1.8-fold (p<0.001) and 1.6-fold (p<0.001) at week 12. The particle size and number of HDL2 were increased up to +10% during the 12 weeks with a remarkable decrease in the TG content, glycation extent, oxidation up to 32% (p=0.032), 18% (p=0.043), and 11% (p=0.023), respectively. The particle number and diameter of HDL3 were increased by up to +9% with a remarkable increase in the PON activity, FRA activity, and TC content of +82% (p<0.001), +56% (p<0.001), and +32% (p=0.009), respectively. Expression of apolipoproteinA-I in HDL2 and HDL3 were significantly elevated more in both gender around 30~48% with more distinct band intensity and less glycation at week 12. These improvements in HDL quality and functionality were linked to the higher survivability of adult zebrafish and their embryos. Under the co-presence of carboxymethyllysine (CML), a microinjection of HDL2 to zebrafish embryo from week 0 resulted in approximately 47% survivability with developmental defects and attenuated speed. On the other hand, the HDL2 microinjection from week 12 resulted in remarkably higher survivability (~ 70%). In conclusion, 12 weeks of Cuban policosanol (Raydel®, 20 mg) consumption with high-intensity exercise showed significant improvement in blood pressure, body fat mass, blood lipid profile without liver damage, CoQ10 metabolism, and renal impairment. At week 12, all participants showed a remarkable decrease in oxidation and glycation extent in the VLDL and LDL with a decrease in the TC and TG content. Significant enhancement of the qualities and functionalities in HDL2 and HDL3 by the policosanol consumption were also detected: increase in apoA-I content, TC content, particle size, and particle numbers along with antioxidant abilities, such as PON and FRA.

This paper analyzes the potential strategies for a bank merger from a Sustainable Development Goals (SDG) perspective, focusing on three key criteria: profitability, market share, and service quality. In the short-term, the merged bank should prioritize optimizing financial performance through cost management, revenue stream identification, and risk management practices. Market share expansion can be achieved through targeted customer acquisition and retention efforts, market research, and competitive analysis. Service quality can be enhanced through improved customer service, efficient complaint resolution processes, and leveraging technology. These short-term plans align the merged bank's operations with the identified criteria and promote responsible banking practices that contribute towards the SDGs. In the long-term, the merged bank should focus on diversifying revenue streams, expanding its customer base, and optimizing cost structure. Long-term strategies should include establishing a strong brand presence, customer loyalty programs, and continuous improvement in service quality. The paper emphasizes the importance of monitoring progress, making necessary adjustments, and aligning with SDGs for sustained profitability and long-term success in the marketplace. The findings of this study provide valuable insights for banks considering a merger and highlight the significance of considering SDGs in their strategic planning.

The Influenza A Virus (IAV) represents an enveloped, positive-sense and single-stranded RNA-based virus that infects mammals mainly via the respiratory system, although other bodily systems are also infected and undergo various extents of inflammatory pathogenesis. There are two well-known strains of IAV that cause life-threatening disease in mammals; H1N1 and H5N1, and the first strain caused the 1918 IAV H1N1 pandemic that claimed between 30 and 50 million human lives. Due to the significant ability of IAV to evade important immune recognition, the virus was observed to favor the onset of secondary microbial infections (i.e. bacterial or fungal), as the overall performance of the immune system became transiently weakened during the viral infection. During the IAV H1N1 pandemic, many patients died as a result of bacterial pneumonia, as pathogenic bacteria, such as Streptococcus pneumoniae and Haemophilus influenzae, gained a wider opportunity to colonize and infect vital areas of the lower respiratory tract, and such a phenomenon led to the excessive, prophylactic usage of antibiotics due to the increased levels of panic, which in turn favored the natural selection of bacteria with genes that became resistant to such antibiotics. Antibiotics might be required for usage solely when bacteria are known to be colonizing vital areas of the human body, and this aspect is tricky, as colonization is asymptomatic and screening is consequently rare. Recently, new variants of the avian IAV H5N1 strain were transmitted from live, infected birds to mammals, including humans in some isolated cases, and given that there have already been several zoonotic spillover events overall since the beginning of 2023, we are rapidly approaching the time when a zoonotic spillover into humans will mark the first epidemic outbreak of the avian flu in humans. A lethality rate of 60% was projected by the World Health Organization, as the virus was shown to favor the development of life-threatening hyper-inflammatory responses at the levels of alveolar tissues constituted by Type II pneumocytes. There are hints that novel variants of H5N1 are capable of infecting the intestinal layer, as recently, two dolphins died as a result of ingesting infected birds within the area of the British Isles. IAV is known to suppress the production and transmission of Type I Interferons by expressing various non-structural proteins (NSPs), such as NSP1, which was found to be also packaged into exosomes and transmitted to neighboring uninfected cells, thereby preventing them from responding to the virus in the first place. A more pronounced rate of innate immune evasion would probably be observed in H5N1 IAV infection than in the infection caused by recent variants of H1N1 IAV. The H5N1 strain of IAV was also found to secrete a higher concentration of NSP1 than SARS-CoV-2, indicating the existence of an association to the greater mortality rate of H5N1 IAV infection. A direct, prophylactic stimulation of the interferon system using a reduced oral or nasal dosage of recombinant anti-inflammatory and anti-viral interferon glycoproteins may represent the most viable approach to prevent an emergence of a life-threatening H5N1 IAV pandemic. A similar non-invasive approach could be developed for an Marburg Virus (MARV) and a Nipah Virus (NiV) infection of humans, as risks of the emergence of a Marburg epidemic and also of a Nipah epidemic may be substantial at this stage as well. Clinical testing of clinical approaches as such could be of critical importance at the moment. Animals could also benefit from related clinical approaches. Somatic natural and adaptive lymphocytes treated with IFN I and III could also constitute a substantial approach of immunization and heavily favor an indefinite shift in the evolutionary battle between the host organism and microbes of public health concern.

Based on the elasticity theory, this paper deals with the static analysis of a cracked double beam system in presence of a Winkler medium. The double-beam system is also supposed to be constrained at both ends by elastically flexible springs, with transverse and rotational stiffness. Using a variational formulation, the static governing equations are derived and solved by using analytical and numerical approaches. In the first approach, the closed-form solutions for the displacements functions are obtained based on the Euler-Bernoulli beam theory. In the second approach, the Cell-Discretization Method (CDM) is performed, according to which the two beams are reduced to a set of rigid bars linked together by means of elastic constraints, where the bending stiffness of the bars is concentrated. The resulting stiffness matrix is easily deduced, and the governing equations of the static problem can be immediately solved. A comparative analysis is performed in order to verify the accuracy and validity of the proposed method. This study focuses on the effect of various parameters including the crack depth and position, boundary conditions, elastic medium and slenderness. The validity of the proposed analysis is confirmed by comparing the present results with those obtained from the other approach. In particular, the results obtained by closed-form solution and Cell-discretization method (CDM) are compared by Finite element method (FEM). Accuracy of the results has been evaluated by making comparisons with the results in literature and reported in bibliography. It is demonstrated that the proposed algorithm provides a simple and powerful tool in dealing with the static analysis of a double-beam system. Finally, some concluding remarks are made.

In this paper it is shown that mathematical description of strain, constitutive law and dynamics obtained by direct replacement of integer order derivatives with Caputo or Riemann-Liouville fractional order partial derivatives, having integral representation on finite interval, in case of a guitar string, is nonobjective. The basic idea is that different observers, using this type of descriptions, obtain different results which cannot be reconciled, i.e. transformed into each other using only formulas that link the coordinates of the same point in two fixed orthogonal reference frames and formulas that link the numbers representing the same moment of time in two different choices of the origin of time measuring. This is not an academic curiosity! It is rather a problem: which one of the obtained results is correct?

Dear Ladies and Gentlemen, I thank you for suggesting to submit the manuscript with the title “Insulin resistance develops due to an imbalance in the synthesis of cyclic AMP and the natural cyclic AMP antagonist prostaglandylinositol cyclic phosphate (cyclic PIP)” to the Editorial Board of the MDPI journal Stresses, and I ask for consideration to publish it in the journal Stresses. It was previously submitted to the MDPI journal Int. J. Mol. Sci. (IJMS-195 6513), but it was found that 1) it would not fit within the scope of this special edition and 2) it would primarily deal with cyclic PIP and would have not enough literature citation on the topic insulin resistance. The present version of the manuscript is improved, but the content is the same. The goal of this review is not to write again a summary on nearly all reports on insulin resistance as this was done by Dr. Petersen and Dr. Shulman, whose review has 961 literature citations. The present manuscript compiles what is known on cyclic PIP in relation to insulin resistance and the reason of writing this manuscript was that the discovered facts on cyclic PIP synthesis allow to suggest how insulin resistance most likely starts. Hitherto, reports on insulin resistance did not come close to this question. I am convinced that the manuscript makes an essential contribution to the question what causes the development of insulin resistance, and I have to say that stress overload is one of the reasons. Unfortunately, I have to mention a topic, about which I do not like to talk. Years ago, research groups postulated with rigor that the mediator of insulin action would be a peptide and then they suggested various, extracellularly synthesized glycans as mediators. They caused confusions and a high degree of disbelief in the matter of mediators of insulin action. In my review on cyclic PIP in IUBMB Life from 2020, I wrote in the introduction that cyclic PIP should not be confused with these mediators. But I cannot write this in the introduction of every report. I am keeping fingers crossed so that the editor in charge will find fair and openminded reviewers. Last not least I confirm that neither the manuscript nor any part of its content is currently under consideration or published in another journal. Kind regards, Henrich Wasner, PhD, BioReg Biopharm, TiLab; University of Illinois at Chicago; 2242 West Harrison St., Ste. 201, Chicago, Il 60612; USA

Current, application-driven trends towards larger-scale integration (LSI) of microfluidic systems for comprehensive assay automation and multiplexing pose significant technological and economical challenges to developers. By virtue of their intrinsic capability for powerful sample preparation, centrifugal systems have attracted significant interest in academia and business since the early 1990s. This review models common, rotationally controlled valving schemes at the heart of such “Lab-on-a-Disc” (LoaD) platforms to predict critical spin rates and reliability of flow control mainly based on geometries, location and liquid volumes to be processed, and their experimental tolerances. In absence of larger-scale manufacturing facilities during product development, the method presented here facilitates the provision of efficient simulation tools for virtual prototyping and characterization to greatly expedite design optimization according to key performance metrics. This virtual in silico approach thus significantly accelerates, de-risks and lowers costs along the critical advancement from idea, fluidic testing, bioanalytical validation and scale-up to commercial mass manufacture.

This study aimed to investigate the healing effect of advanced platelet-rich fibrin (A-PRF) clot membranes in the reduction of palatal wounds resulting from free gingival graft (FGG) harvesting, in the re-epithelization rate and in the pain experience after surgery. Twenty-five patients requiring soft tissue augmentation (gingival recession coverage or keratinized gingiva augmentation) participated in this prospective randomized clinical study. After FGG harvesting, the test group (n=14) received A-PRF clot membranes at the palatal wound and the control group (n=11) a gelatin sponge. Epithelialization rate of the palatal wound, wound healing area, correspondent percentage of reduction and post-surgical pain experience were assessed. The follow-up period was 90 days. There was a significantly higher reduction of the palatal wound area in the A-PRF group vs. the control group, at 7 (p<0.001), 14 (p=0.009) and 30 days (p<0.001) follow-up. The maximum difference between groups was attained at 30 days (91.5% for A-PRF vs. 59.0% for the control group). At 14 days a significant difference in the proportion of patients showing total epithelization was found: 64.3% for A-PRF vs. 9.1% for the control group (p=0.012). At 90 days, both groups showed total recovery. Overall, the control group experienced a higher level of pain and discomfort until the 14th day, being significantly higher on the second day (p=0.013). The results suggest that A-PRF membranes haste the healing process by promoting a greater reduction along the recovery period and an apparent less painful postoperative period.

This paper reviews the low-resilience problem in many cities, poor designs of cities to cope with disasters, and the need for tolerance of urban constructions. It explores answers concerning the question of how shall we build cities resiliently? The method of this applied research is a multiphase process that considers all physical and socioeconomic elements of a city. It introduces six indicator groups of urban management (M), economy (E), built environments (U), Infrastructures (I), natural environments (N), and health protection (H). The groups include 55 indicators as variables in the mathematical calculations in this paper. This paper builds a mathematical model to maximize the profitability of resilient buildings by optimizing investments in the required projects. The projects will upgrade the firmness and tolerance of cities against nature-based and human-made dangers and risks. There is a linear programming in 55 variables to select optimal solutions from fifty-five factorial alternatives. Then, the programming will develop into non-linear programming. The unique innovation of this paper is its linear programming interpretation by non-linear to give optimal solutions for the problem. Applying the Lagrange function in the Kuhn-Tucker conditions proves the accuracy of the hypothesis that post-COVID urbanization requires maximum resilience. Only in this way, the urban economies will be free of risks. Outcomes in this paper will assist in the pre-planning, design, and building of built environments everywhere resilient and sustainable.

One method of estimating the evaporation rate (ER) is to use a variety of evaporation pans, such as the Class A standard evaporation pan (CASEP) and the Colorado Sanken standard evaporation pan (CSSEP). In this study, the rate of evaporation of CASEP and CSSEP have been investigated and compared with each other. This study was conducted in Semnan, Iran. CSSEP was used as a test pan, which was performed in an open space around the Faculty of Civil Engineering, Semnan University. Evaporation was recorded daily for 123 days. The evaporation of the CASEP pan was obtained from the synoptic station of Semnan, which is located at a distance of 2.39 km from the test site. Meteorological data were also obtained from the synoptic station of Semnan and compared with experimental evaporation data. The results of this study showed that the daily ER from CASEP and CSSEP in the tested time periods were not significantly different. Based on the Klomogorov-Sminrov method, the best statistical distributions for CASEP and CSSEP were calculated as Error and Gamma, respectively. The coefficient of determination (R 2 ) between the two pans was estimated to be about 93%. Also, by examining the ER with other meteorological data, it was observed that the ER has the highest correlation with the average daily air temperature.

The aim of this work is to broaden the theory of computation by making use of fuzzy sets and multisets, which are generalization of ordinary sets. We study fuzzy multiset finite automata (FMFA), which are characterized by the incorporation of vagueness when it comes to the choice of the next state and multiple occurrences of the same input symbol. The resulting automaton is a genaralization of both classical automata and fuzzy automata. We discuss the algebraic characteristics of FMFA sub-automata—separatedness, strongly connectedness, cyclic, directable, and triangular FMFA in terms of equivalence classes induced by an equivalence relation defined on state set of FMFA. Intrestingly, for a given FMFA, a new FMFA can be constructed that is a homomorphic image of the original FMFA. We define different posets structures that can be associated with a given FMFA and show that some of them are upper semilattices and discuss the inter-relationship of a given poset, a finite upper semilattice (FUSL), a FMFA and a posets/FUSL associated with a given FMFA. Finally, we introduce the concept of decomposition of a FMFA in two different ways and characterize the strongly connected, triangular and directable FMFA.

Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 hours in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials.

Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available. PAPP-A is a protein that is highly elevated during pregnancy. Frequently, higher PAPP-A expression is detected in tumors than in healthy tissues. The increase in expression coincides with increased rates of aggressive cancers. In BC, PAPP-A has been demonstrated to play a role in tumor initiation, progression, metastasis including epithelial-mesenchymal transition (EMT), as well as acting as a biomarker for predicting patient outcomes. In this review, we present the role of PAPP-A, with specific focus on TNBC. The structure and function of PAPP-A, belonging to the pappalysin subfamily, and its proteolytic activity are assessed. We highlight the link of BC and PAPP-A with respect to the IGFBP/IGF axis, EMT, the window of susceptibility and the impact of pregnancy. Importantly, the relevance of PAPP-A as a TNBC clinical marker is reviewed and its influence on immune-related pathways are explored. The relationship and mechanisms involving PAPP-A reveal the potential for more treatment options that can lead to successful immunotherapeutic targets and the ability to assist with better predicting clinical outcomes in TNBC.

Artificially designed, chimeric peptide-based recombinant vaccines are novel approaches to combat the phylogenetically diverse Foot and Mouth Disease (FMD) Virus (FMDV) strains. Among seven distinct serotypes, only serotype O and A are dominantly circulating in Bangladesh and neighbouring countries of Asia, where transboundary transmission, recurrent outbreaks and emergence of novel lineages FMDV are highly prevalent. The objective of this study was to develop multi-epitope recombinant peptides, procuring immunogenicity against circulating diverse subtypes of FMDV serotype O and A. Two chimeric peptides, named B1 (41.0 kDa) and B3 (39.3 kDa), have been designed to incorporate potential B-cell and T-cell epitopes selected from multiple FMDV strains, including previously reported and newly emerged sub-lineages. After expression, characterization and immunization of guineapigs with considerable antigen load of B1 and B3 followed by the serological assays revealed the significant protective immunogenicity, developed from the higher (100 µg) doses of both antigens, against most of the currently prevalent serotype O and A strains of FMDV. The efficient expression, antigenic stability, and multivalent immunogenic potency of the chimeric peptides strongly indicate their credibility as novel vaccine candidates for FMDV serotypes O and A circulating in Bangladesh and surrounding territories.

Abstract: Background: Neonatal sepsis continues to be one of the leading causes of mortality and morbidity, particularly in under development and underdeveloped countries. We aim to compare laboratory parameters between the early-onset sepsis (EOS) and non-EOS groups and to evaluate the association between TLR2- Arg753Gln, TLR4 -Asp299Gly, IL6-174G/C and IL10-1082G/A gene single nucleotide polymorphisms and EOS susceptibility in preterm newborns. Methods: Genotyping of the TLR2, TLR4, IL6 and IL10 polymorphisms was performed in 36 preterm neonates by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP). Logistic regression analysis was used to test the associations between the studied gene polymorphisms and EOS susceptibility. Results: Statistically significant differences in gestational age and birth weight were observed between the two groups, preterm neonates with EOS having a lower mean of gestational age (weeks, 29.4 ± 2.8 versus 32.6 ± 1.1, p = 0.00002) and lower mean of birth weight (gr., 1342.1 ± 446.5 vs. 1984 ± 376.9) than preterm neonates without EOS. C-reactive protein (CRP) values measured at first day significantly increased in EOS group compared with non-EOS group (median, 95% CI: 0.80 [0.40, 1.15] versus 0.30 [0.02, 0.50]). Mean of neutrophils significantly decreased in the EOS preterm neonates (mean difference: 17.3%, 95% CI: [4.0%, 30.5%], p = 0.0126) and non-EOS group (mean difference: 20.8%, 95% CI: [1.8%, 39.9%, p = 0.0354) between the first day and 7th hospitalization day. The minor IL10-A1082 allele frequency was higher in the EOS group than in the nonEOS group (50% versus 25%) with a marginal statistical significance (p=0.0550). In the dominant model, the A/G + A/A variant genotype of IL10- 1082G/A polymorphism significantly increased the odds of EOS compared with GG genotype (OR= 5.25, p = 0.0322). Conclusions: The results of the current study suggests the IL10- 1082G/A gene polymorphism as significant risk factor for early onset sepsis development in preterm neonates.

(1) Background: Deep hypothermic circulatory arrest (DHCA) with selective antegrade cerebral perfusion (ACP) is an established cerebral protection technique for the conduction of complex surgical procedures involving the aortic arch. It is controversial if the duration of DHCA is associated with adverse outcome in patients with acute type A aortic dissection (AAAD). Our goal was to investigate whether DHCA time was associated with surgical outcome in patients undergoing a surgical treatment of AAAD. (2) Methods: 410 Patients were divided into two groups concerning the DHCA time less than 60 minutes and equal or longer than 60 minutes. (3) Results: Patients with longer DHCA time were significantly younger (p=0.001). Intraoperatively, complex procedures with aortic arch surgery were more common in patients with longer DHCA time (p&lt;0.001). Accordingly, cardiopulmonary bypass (p&lt;0.001), cross-clamping (p&lt;0.001) and DHCA times (p&lt;0.001) were significantly longer in this group. Postoperatively, only the duration of mechanical ventilation (p&lt;0.001) and the rate of tracheotomy were significantly higher in these patients. 30-day mortality was satisfactory for both groups (p=0.746). (4) Conclusions: Our results showed that improvements in perioperative management including ACP allow a successful performance of surgical treatment of AAAD under DHCA with duration of even longer than 60 minutes.

Replication protein A (RPA) is a heterotrimeric protein complex and the main single-stranded DNA (ssDNA) binding protein in eukaryotes. RPA has key functions in most of the DNA-associated metabolic pathways and DNA damage signalling. Its high affinity for ssDNA helps to stabilise ssDNA structures and prevents the DNA sequence from nuclease attacks. RPA consists of multiple DNA-binding domains which are oligonucleotide/oligosaccharide-binding (OB)-folds, responsible for DNA binding, and interactions with proteins. These RPA-ssDNA and RPA-protein interactions are crucial for DNA replication, DNA repair, DNA damage signalling, and the conversation of the genetic information of cells. Proteins such as ATR use RPA to locate to regions of DNA damage for DNA damage signalling. Recruitment of nucleases and DNA exchange factors to sites of double strand breaks are also an important RPA function to ensure effective DNA recombination to correct these DNA lesions. Due to its high affinity to ssDNA, RPA’s removal from ssDNA is of central importance to allow these metabolic pathway to proceed and processes to exchange RPA against downstream factors are established in all eukaryotes. These facetted and multi-layered functions of RPA will be discussed in detail in the review. RPA is also a major player in a variety of human diseases, which will be discussed.

Polycyclic aromatic hydrocarbons (PAHs) have been reported to cause oxidative stress in metabolic processes. This study aimed to evaluate the relationship between exposure to PAHs, including benzo[a]pyrene (BaP) and 1-nitropyrene (1-NP), in the atmosphere and oxidative stress levels in the human body. This study included 44 Korean adults who lived in Cheongju, South Korea. Atmospheric BaP and 1-NP concentrations and urinary 6-hydroxy-1-nitropyrene (6-OHNP), N-acetyl-1-aminopyrene (1-NAAP), and 1-hydroxypyrene (1-OHP) concentrations were measured. The oxidative stress level was assessed by measuring urinary thiobarbituric acid reactive substances (TBARS) and 8-hydroxydeoxyguanosine (8-OHdG) concentrations. Urinary TBARS and 6-OHNP concentrations significantly differed between winter and summer. BaP exposure was significantly associated with urinary 8-OHdG concentrations in summer. However, atmospheric 1-NP did not show a significant correlation with oxidative stress marker concentrations. Urinary 1-NAAP concentration was a significant determinant for urinary 8-OHdG concentration in summer. Oxidative stress in the body increases in proportion to inhalation exposure to BaP, and more 8-OHdG is produced in the body as the amount of 1-NP, which is metabolized to 1-AP or 1-NAAP, increases.

Bisphenol-A (BPA) represents an important co-monomer for obtaining polycarbonate, epoxy resins, flame retardants, in paint, and other chemicals products. Products containing BPA are widely used, and thus, we can find it in the environment: in the air, in the soil, in natural surface water and in sediments, underground water in landfills, and in wastewater. BPA disturbs human and animals’ health. This influences the enzymatic, androgenic, neurological, liver and reproductive systems at different stages of human life: like in fetal stage, children and adults’ stages. Taking these inconveniences into account, it is very important to remove BPA from water. Ultrasonic technology can be considered a verry sustainable and efficient method to remove BPA from water. The advantages of this method is easy to implement on existing water treatment and purification facilities, it does not produce residual compounds that produce sludge, the time required for degradation is of the order of 1-2 hours and the level of degradation is very high. In this work, we presented the studies on the efficiency of ultrasonics under air atmosphere on the degradation of BPA. The influence of the frequency and of some additional compounds such as carbon tetrachloride, FeSO4 7H2O (FS), and ethyl anthraquinone (EAC) was studied. Three different frequencies were used: 1146 KHz, 864 KHz, 580 KHz, at a power of 50 W. It was identified the efficiency of BPA degradation over a period of 60 minutes, with sampling every 15 minutes. Using the LC-MS/MS technique, the degradation compounds were identified that result from the application of ultrasound processes. Pathways of BPA degradation were also proposed.

Using the principle of equivalence, it has recently been shown that the electrostatic field lines of a charge, stationary in the gravitational field, bend exactly like the trajectories of photons emitted isotropically from a source at the charge location and that the fraction of electric flux crossing a surface `below' or `above' the charge is exactly similar to the fraction of photon trajectories intersecting these surfaces, with more flux in the downward direction than upward. As one goes much deeper in the gravitational field, all electric field lines increasingly point in the vertically downward direction as is also the case for a stream of photons. Since photon trajectories as well as electric field lines, at any location in the gravitational field, are affected by the local space-time curvature an inference can be drawn that this parallel between the photon trajectories and the electric field lines is a general result. We could then apply these results in the external gravitational field of a black hole, where the trajectories of photons in the gravitational field are already well-known and the behaviour of electric field lines of a stationary charge could be inferred therefrom. Accordingly, we show that the electric field through an external spherical surface surrounding the black hole steadily reduces as the charge location approaches the event horizon (Schwarzschild radius), and like photons from a source inside the Schwarzschild radius cannot escape outside, the electric field lines of a charge within the black hole too remain trapped inside the event horizon. From this one arrives at a conclusion that, contrary to the conventional wisdom, the electric charge contained inside a static black hole cannot be detected or inferred by an external observer. A black hole, said to have no hair with the only external identifying characteristics being mass, electric charge, and angular momentum, is therefore all the more `hairless', as even its charge cannot be ascertained. The derivation of the Reissner-Nordström metric, supposedly describing the gravitational field of a static charged black hole, presumes an external stress-energy tensor of the electrostatic field, as per Gauss law, even for the charges contained within the black hole. However, the absence of electric flux external to a static charged black hole implies that such a charged black hole is not described correctly by the Reissner-Nordström metric and the consequential peculiarities of the space-time geometry, leading in specific cases to the idea of a naked intrinsic singularity and a need for the ``cosmic censorship'' hypothesis, also do not arise here.

Infectious bursal disease (IBD) is a viral poultry disease known worldwide for impacting the economy and food security. The disease is endemic in Nigeria, with reported outbreaks in vaccinated poultry flocks. To gain insight into the dynamics of infectious bursal disease virus (IBDV) evolution in Nigeria, near-complete genomes of four IBDVs were evaluated. Amino acid sequences in the hypervariable region of the VP2 revealed conserved markers (222A, 242I, 256I, 294I and 299S), associated with very virulent (vv) IBDV, including the serine-rich heptapeptide motif (SWSASGS). Based on the newly proposed classification for segments A and B, the IBDVs clustered in the A3B5 group (where A3 are IBDVs with vvIBDV-like segment A and B5 are from non-vvIBDV-like segment B) forming a monophyletic subcluster. Unique amino acid mutations with yet-to-be-determined biological functions have been observed in both segments. Amino acid sequences of the Nigerian IBDVs showed that they are reassortant viruses. Circulation of reassortant IBDVs may be responsible for the vaccination failures observed in the Nigerian poultry population. Close monitoring of changes in the IBDV genome is recommended to nip deleterious changes in the bud, through the identification and introduction of the most appropriate vaccine candidates and advocacy/extension programs for properly implementing disease control.

Digital microfluidics (DMF) holds great potential for the alleviation of laboratory procedures in assisted reproductive technologies (ARTs). Electrowetting on dielectric (EWOD) provides dynamic culture conditions in vitro that may better mimic the natural embryo microenvironment. Thus far, EWOD microdevices have been proposed for in vitro gamete and embryo handling in mice and for analyzing the human embryo secretome. This article presents the development of the first microfluidic chip utilizing EWOD technology designed for the manipulation of bovine embryos in vitro. The prototype sustains the cell cycles of embryos manipulated individually on the chips during in vitro culture (IVC). Challenges related to the chip fabrication as well as to its application during bovine embryo IVC in accordance with the adapted on-chip protocol are thoroughly discussed, and future directions for DMF in ARTs are indicated.

This work presents the results of a computational study of the chemical reactivity and bioactivity properties of the members of the Theopapuamides A-D family of marine peptides by making use of our own proposed methodology named Computational Peptidology (CP) that has been successfully considered in previous studies of this kind of molecular systems. CP allowed for the determination of the global and local descriptors that come from Conceptual Density Functional Theory (CDFT) that can give an idea of the chemical reactivity properties of the marine natural products under study which are already known to be related to their bioactivity. At the same time, the validity of the procedure based on the adoption of the KID (Koopmans in DFT) technique as well as the MN12SX/Def2TZVP/H2O model chemistry has been successfully verified. Together with several Chemoinformatic tools that can be used for the improvement of process of Virtual Screening, some additional properties of these marine peptides were identified related to their ability to behave as useful drugs. With the further object of analyzing their bioactivity some parameters of usefulness for future QSAR studies, their predicted biological targets and the the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) parameters related to the Theopapuamides A-D pharmacokinetics are also reported.

This work reports the isolation, purification, and anti-inflammatory evaluation of compounds from the plant species Ageratina pichinchesis. Using open-column chromatography, 11 known compounds were purified, whose chemical structures were elucidated by nuclear magnetic resonance techniques (1D and 2D). All compounds were evaluated in the in vitro model of RAW 264.7 mouse macrophage cells measuring nitric oxide inhibition as a determination of the anti-inflammatory effect. Outstandingly, the compound betuletol 3-O-β-glucoside (11) exhibited inhibition of nitric oxide with an IC50 of 75.08 ± 3.07% at 75 µM, additionally, it inhibited the secretion of interleukin 6 (IL-6) and activation of nuclear factor (NF-kβ). These results show that compound 11 could be considered as a potential anti-inflammatory agent in suppressing the expression of NF-kβ target genes such as the proinflammatory pathway and inducible nitric oxide synthase (iNOS). Consequently, the medicinal use attributed in traditional medicine to the A. pichinchensis species is due to the diversity of compounds that the plant biosynthesizes, demonstrating that its effect relates to anti-inflammatory effects associated with compound 11.

Cardiovascular diseases (CVD) are chronic diseases associated with a high risk of mortality and morbidity. Early detection of CVD is crucial to initiating timely interventions, such as appro- priate counseling and medication, which can effectively manage the condition and improve patient outcomes. Preventive measures should be implemented at the general public level, promoting a healthy lifestyle, and at the individual level, that is, in people with moderate to high risk of CVD or patients already diagnosed with CVD by addressing an unhealthy lifestyle. Personalized early diagnostic systems based on artificial intelligence (AI), ontologies, and other medical information processing systems may prove to be a great preventive measure. In this paper, we focus on the use of ontology-inspired database models in the diagnosis of cardiovascular disease, as well as their potential for use in web application development.

The amino acids (AAs) and vitamins imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFβ in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. Plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p=0.04) and an increase in IL-2 (p=0.008) and IL-12 (p=0.007) mRNA expression compared to HCs. Treated adult patients showed elevated Serine (p=0.003) and Glycin (p=0.04) levels, as well as increased IL-12 (P&lt;0.0001) mRNA expression, and a decrease in Tryptophan (p=0.04) levels relative to the controls. Additionally, treated adult patients had higher plasma levels of Threonine compared to both active (p=0.04) and control (p=0.02) subjects, and increased mRNA expression of IL-4 (p=0.01) in comparison to active patients. In active children with CD, IL-2 mRNA level was found to be higher than in controls (P&lt;0.0001) and in treated children (p=0.005). Treated children with CD exhibited decreased plasma levels of Tryptophan (p=0.01) and Isoleucine (p=0.01) relative to the controls, and increased mRNA expression of TGFβ (p=0.04) relative to active patients. Managing Retinoic acid levels is crucial to alleviate intestinal inflammation of CD patients. Threonine, tryptophan, and Isoleucine are potential therapeutic options for treating CD, and targeting serine, histidine, tyrosine, and aspartate may hold promise as therapeutic targets for CD patients.

The present studies were undertaken to address the role of fetuin-A in the growth and invasion potential in a triple negative breast cancer (TNBC) cell line, MDA-MB-468. Basal like TNBC that express high levels of ectopic fetuin-A have poorer prognosis for the patients compared to those that express low levels of the protein. We overexpressed fetuin-A in MDA-MB-468 and then determined the invasive potential of fetuin-A overexpressing cells vs controls transfected with empty vector. We also determined the adhesion and growth potential of the cells in the presence of only fetuin-A in serum free medium and also in complete medium. Our data suggest that fetuin-A overexpression significantly enhances the invasive potential of the cells and also the expression of Toll like receptor 4 (TLR4) on these cells. More importantly, the cells rely on fetuin-A-TLR4 signaling network for growth and invasion because the specific TLR4 inhibitor CLI-095 (resatorvid) abrogates fetuin-A mediated growth and invasion. Taken together, the data suggest that fetuin-A-TLR4 signaling network plays a significant role in the growth and invasion potential of TNBC.

Background: It is known that Preeclampsia affects the lactogenesis. However, data on effects of this pathology on the human milk neurobiomarkers composition are not available. The aim of this study is to investigate the effects of this gestational pathology on Activin A levels, a neurobi-omarker known to play an important role in the development and protection of the central nerv-ous system. Methods: The women recruited were divided in two different study groups: preeclamptic or normotensive women. All the human milk samples were collected using the same procedure. Activin A was quantified using an ELISA test. To investigate the effect of Preeclampsia on the Activin A concentration in the 3 lactation phases, mixed linear model with unistructural covariance structure, mother as random effect, and fixed effects were performed. Results: Activin A was detected in all samples. There were no significant differences between Preeclamptic and Normotensive women. The only significant effect is related to the lactation phase: it is significant the difference between colostrum and mature milk (p<0.01). In conclusion these results allow us to affirm that breast milk beneficial properties are maintained even if preeclampsia occurs.

The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352-372) is highly conserved (>90% in 90% species) in mammalian species. The highest-evolved primates show 58.8% similarity with the lowest-evolved monotremes. CST was initially identified as a physiological brake in catecholamine secretion by inhibiting nicotinic-cholinergic signaling. CST also inhibits desensitization of catecholamine secretion, indicating that CST can act both as a cholinergic antagonist (short-term) and as a cholinergic agonist (long-term). The long-term effect sustains catecholamine secretion during stressful situations. CST is now established as a pleiotropic hormone: it affects the cardiovascular system by lowering blood pressure and cardiac contractility, enhancing baroreflex sensitivity, increasing heart rate variability, and promoting angiogenesis; and it increases insulin sensitivity by reducing inflammation, inhibiting hepatic glucose production, attenuating endoplasmic reticulum stress, and inducing glycogen production. The present review will highlight the important direct and indirect effects of CST, CST1-15 (aka cateslytin), D-CST1-15 (where L-amino acids were changed to D-amino acids), and human variants of CST (Gly364Ser-CST and Pro370Leu-CST) on microbial growth inhibition and their potential as therapy for antibiotic-resistant pathogenic microbes.

Lyme disease (LD) is a tick-transmitted infection caused by Borrelia burgdorferi sensu lato species which includes B. burgdorferi, B. afzelii, and B. garinii. The majority of patients with early LD can be cured by standard treatment, yet some still suffer from post-treatment Lyme disease syndrome (PTLDS). The presence of Borrelia persisters has been proposed as a contributing factor, which cannnot be completely killed by the currently used antibiotics for Lyme disease. Finding new pharmaceuticals targeting Borrelia persisters is crucial in developing more effective treatment. Here, we first confirmed the existence of persisters in cultures of B. garinii and B. afzelii and then conducted high-throughput screening of a custom drug library against persister-rich stationary-phase cultures of B. garinii and B. afzelii. Among 2427 compounds screened, hypocrellin A (HA), anthracycline class of drugs, and topical antibiotics along with some other natural compounds were identified to have strong potential in killing persisters of B. garinii and B. afzelii. HA was the most active anti-Borrelia compound, capable of eradicating stationary-phase Borrelia persisters, in particular when combined with doxycycline and/or ceftriaxone. Liposoluble antioxidant vitamin E was found to antagonize the activity of HA, indicating HA’s target is the cell membrane where HA-triggered reactive oxygen species (ROS) generation took place in the presence of light. HA was found to have distinct bactericidal activity against Borrelia species but had poor or no activity against Gram-positive and Gram-negative bacteria. Identification of the above-mentioned drug candidates may help to develop more effective therapies for LD.

Benzo[a]pyrene (B[a]P), is a family member of polycyclic aromatic hydrocarbons and a widespread environmental pollutant and neurotoxicant that contribute to the development of cancer. Microtubules are polymers of tubulin that form part of the cytoskeleton and target for anticancer drugs. Furthermore, NPY significantly increased the percentage of cells in S and G2/M phases. However, little is known about the specific role of NPY in proliferation and the underlying protective mechanism remains unclear. Hence, the aim of this work was to investigate the effect of B[a]P on SH-SY5Y neuroblastoma cells and to explore the potential mechanism for alteration of tubulin-microtubule equilibrium causing mitotic arrest and NPY expression. The present findings showed B[a]P treatment significantly increase number of SH-SY5Y cells in S and G2/M phase as compared to G1 phase and provokes cell cycle arrest that correlated with significant decrease in G0/G1 cells. Immunofluorescence study showed significantly distorted tubulin arrangement from metaphasic plate in formation of bipolar mitotic spindle apparatus. Further, higher doses of B[a]P treatment lead to chromosomal abnormalities accompanied by DNA damage due ROS causing oxidative stress showing significant decrease in tubulin protein around spindle. The results of present study demonstrated that NPY exerts a proliferative and protective effect on B[a]P-induced oxidative stress in a dose-dependent manner in vitro and importantly, these effects may be mediated via mitotic arrest and involved in spindle arrangement during cell division. Our findings addresses a novel pathological outcomes of B[a]P-induced NPY expression by oxidative stress through spindle abnormalities leading to microtubule disruption.

Surface Plasmon Resonance (SPR) based sensors have the advantage of being label-free, enzyme-free and real-time. However, their spreading in multidisciplinary research is still limited and almost confined to prism-coupled devices. Plasmonic gratings, combined with a simple and cost-effective instrumentation, have been poorly developed compared to prism-coupled system mainly due to their lower sensitivity. Here we describe the optimization and signal enhancement of a sensing platform based on phase-interrogation method, which entails the exploitation of a nanostructured sensor. This technique is particularly suitable for integration of the plasmonic sensor in a lab-on-a-chip platform and can be used in a microfluidic circuit to ease the sensing procedures and limit the injected volume. The careful optimization of most suitable experimental parameters by numerical simulations leads to a 30 to 50% enhancement of SPR response, opening new possibilities for applications in the biomedical research field while maintaining the ease and versatility of the configuration.

The alkylation of 1,1,2-trimethyl-1H-benzo[e]indole with 2-chloroacetamide, followed by work-up of the reaction mixture with a base and the subsequent treatment of a crude product with acetic acid gives 10a,11,11-trimethyl-10a,11-dihydro-8H-benzo[e]imidazo[1,2-a]indol-9(10H)-one. The structure assignments were based on data from ¹H, ¹³C and ¹⁵N NMR spectroscopy. The optical properties of the obtained compound were studied by UV-vis and fluorescence spectroscopy.

In this work modeling and analysis of an integrated opto-fluidic sensor, with a focus on achievement of single mode optical confinement and continuous flow of micro particles in the microfluidic channel for Lab-on-a Chip (LOC) sensing application is presented. This sensor consists of integrated optical waveguides, microfluidic channel among other integrated optical components. A continuous flow of micro particles in a narrow fluidic channel is achieved by maintaining the two sealed chambers at different temperatures and by maintaining a constant pressure of 1Pa at the centroid of narrow fluidic channel geometry. The analysis of silicon on insulator (SOI) integrated optical waveguide at an infrared wavelength of 1550nm for single mode sensing operation is presented. The optical loss is found to be 0.0005719dB/cm with an effective index of 2.2963. The model presented in this work can be effectively used to detect the nature of micro particles and continuous monitoring of pathological parameters for sensing applications.

This article lays the foundation for Extended Relativity (ER) – a unified geometric approach to the electromagnetic and gravitational field and relativistic dynamics in them. We explain here the basic tenets of ER, including the influenced spacetime of an object and the Extended Principle of Inertia. These two new ideas enable a unified theory of these fields. We introduce local scaling functions for describing the geometry of a spacetime influenced by a field and construct a simple, universal local scaling function which unifies electromagnetism and gravity. We recover the full electromagnetic theory, including Maxwell’s equations. For gravitation, ER passes all of the tests of General Relativity. Despite the non-linearity of relativistic gravitation, we obtain a method of combining fields from multiple sources. Finally, we identify the differences in the relativistic treatment of the electromagnetic field by Special Relativity and of the gravitational field by General Relativity and indicate how these differences are resolved in ER.

One of the most widely available and extensively produced varieties of industrial hemp, which generates a substantial amount of consumer-increasing waste in the form of hemp cellulose. In this study, recycling with a compressed and high-speed method that combines crushing and alkali treatment effectively converts leftover hemp fiber into ultrafine powder. SEM (Scanning Electron Microscopy), AFM (Atomic Force Microscope), FTIR (Fourier-transform Infrared Spectroscopy), and XRD (X-ray Diffraction) examined the original morphology of hemp fiber treated with alkali, fiber heated to 200 ℃, and crushed powder. Particle size, crystallinity, fiber surface, and strength increased and decreased. It became apparent that fiber strength decreased and fiber roughness significantly increased after alkali treatment. Fiber increased significantly, and crystallinity decreased after crushing. It was simple and effective for converting the leftover hemp fiber into micron-sized powder. In about 3 to 5 minutes, approximately 1 kg of dry ultrafine powder with a particle size of 10.44 μm was produced. This production method will significantly enhance future industrial applications of waste hemp fiber.