In the present study. At first, some properties of r-fuzzy soft β-closed sets are introduced on fuzzy soft topological spaces based on the paper Aygunoglu et al. (Hacet. J. Math. Stat. 2014, 43, 193-208). Also, we define the closure and interior operators with respect to the classes of r-fuzzy soft β-closed and r-fuzzy soft β-open sets, and investigate some of their properties. In addition, the concept of r-fuzzy soft β-connected sets is introduced and characterized with help of fuzzy soft β-closure operators. Thereafter, some properties of a fuzzy soft β-continuity are studied. Furthermore, we introduce and study the concepts of fuzzy soft almost (weakly) β-continuous functions, which are weaker forms of a fuzzy soft β-continuity. Also, the relationships between these classes of functions are specified with the help of some illustrative examples. Finally, we explore new types of fuzzy soft functions called, fuzzy soft β-irresolute (strongly β-irresolute, β-irresolute open, β-irresolute closed and β-irresolute homeomorphism) functions, and discuss some properties of them. Also, we show that fuzzy soft strongly β-irresolute → fuzzy soft β-irresolute → fuzzy soft β-continuity, but the converse may not be true.

In this paper, some characterizations of fuzzifying strong compactness are given, including characterizations in terms of nets and pre -subbases. Several characterizations of locally strong compactness in the framework of fuzzifying topology are introduced and the mapping theorems are obtained.

Background: Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer’s disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show membrane-binding capacity to red blood cells (RBCs) and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Aβ-treated RBCs. Methods: In RBCs following different treatments, ATP, 2,3 DPG, cAMP levels, and caspase 3 activity were determined by spectrophotometric and immunoassay. Results: S1P rescued the inhibition of ATP release from RBCs triggered by Aβ through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. Conclusions: These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.

Weak interaction processes continue to be hot topics in fundamental physics research. In this paper, we briefly review some recent advances in the theoretical study of beta and double-beta decays that include both the nuclear and atomic part of these processes. On the nuclear side, we present a statistical approach for the computation of the nuclear matrix elements (NME) for neutrinoless double-beta (0νββ). A range of NME values, the most probable value for NME, and the associated theoretical uncertainty are given. Correlations with other related observables are shown as well. On the atomic side, we first briefly review the methods used to get the electrons’ wave functions. Further, we use them for the computation of some relevant kinematic quantities such as Fermi functions, electron spectra and angular correlation between the emitted electrons. Then, we present applications of these calculations to the experimental data analysis related to the search of the Lorentz invariance violation in two-neutrino double-beta (2νββ) decay and description of the decay rates and decay rate ratios for allowed and unique forbidden electron capture (EC) processes.

We define the notions of strong and strict recurrency for actions of countable ordered groups on $\sigma$-finite non atomic measure spaces with quasi-invariant measures. We show that strong recurrency is equivalent to non existence of weakly wandering sets of positive measure. We also show that for certain p.m.p ergodic actions the system is not strictly recurrent, which shows that strong and strict recurrency are not equivalent.

The human landscape transforming activity contributes to the global change of vegetation in different forms. Hunting is one of the most ancient human landscape-shaping activities. Feeders for hunting are particularly disruptive to vegetation. In the present study, we conducted a vegetation survey in these highly disturbed places. We are investigating the vegetation dynamics over several years in in the turkey oak–sessile oak zone, in two areas with different moisture and shade conditions (forest and clearing). One important background factor is changes in precipitation and temperature. The novelty of our present study lies in the fact that the observation takes place with continuous disturbance, where the human influence is very large. Our results confirm that the weed infestation be detectable at bait sites over a long period, and the interannual changes were typical in every year, according to the fact that in August, more weed species are usually present with a greater cover at the bait sites. The main meteorological factors played a role in the degree of weed infestation in each year. There was a higher proportion of vegetation regeneration in wetter years, while dry periods do not favor successional processes. With the drying of the climate, the disturbed areas are constantly losing their natural value, but wetter weather is not an automatic solution either. A more precise understanding of vulnerable systems and careful planning of treatment interventions is necessary.

In this paper, we present a new concept of the generalized core orthogonality (called the C-S orthogonality) for two generalized core invertible matrices $A$ and $B$. $A$ is said to be C-S orthogonal to $B$ if $A^{\tiny\textcircled{S}}B=0$ and $BA^{\tiny\textcircled{S}}=0$, where $A^{\tiny\textcircled{S}}$ is the generalized core inverse of $A$. The characterizations of C-S orthogonal matries and the C-S additivity are also provided. And the connection between the C-S orthogonality and C-S partial order has been given using their canonical form. Moreover, the concept of the strongly C-S orthogonality is defined and characterized.

A procedure, dedicated to superconductivity, is extended to study the properties of interacting electrons in normal metals in the thermodynamic limit. Each independent-electron band is shown to split into two correlated-electron bands. Excellent agreement is achieved with Bethe's wave-function for the one-dimensional Hubbard model. The groundstate energy, reckoned for the two-dimensional Hubbard Hamiltonian, is found to be lower than values, obtained thanks to the numerical methods. This analysis applies for any spatial dimension and temperature.

A technique devised some years ago permits to study a theory in a regime of strong perturbations. This translate into a gradient expansion that, at the leading order, can recover the BKL solution. We solve exactly the leading order equations in a spherical symmetric case and we show that the 4-velocity in such a case is multiplied by an exponential warp factor when the perturbation is properly applied. This factor is always greater than one. We will give a closed form solution of this factor for a simple case. Some numerical examples are also given.

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

Cercospora beticola Sacc. is an ascomycete pathogen that causes Cercospora leaf spot in sugar beets (Beta vulgaris L.) and other related crops. The disease symptoms are characterized by circular lesions with an ash-gray centre and dark brown to purple margins on the leaves. It can lead to significant yield losses if not effectively managed. This study aims to characterize and assess the impact of bacterial biological control agents against C. beticola. Following a dual-culture screening, 18 bacteria exhibiting over 50% inhibition were selected, with six of them demonstrating more than 80% control. Identification of the bacteria was carried out through sequencing of the16S rDNA, revealing potentially 12 species belonging to six genera including Bacillus which was represented by four species. Additionally, the bacteria underwent in-depth characterization of biochemical and molecular properties, as well as plant-growth promotion. PCR detection of genes responsible for producing antifungal metabolites revealed that 83%, 78%, 89%, and 56% of the selected bacteria possessed the bacillomycin, iturin, fengycin, and surfactin encoding genes, respectively. Infrared spectroscopy analysis confirmed the presence of lipopeptide structure in the bacteria supernatant filtrate. Subsequently, the bacteria were assessed for their effect on sugar beet plants in controlled conditions. The bacteria exhibited notable capabilities, promoting growth in both roots and shoots, resulting in significant increases in root length, weight, and shoot length. The field experiment with four bacterial candidates demonstrated good performance against C. beticola compared to difenoconazole fungicide. These bacteria played a significant role in disease control, achieving a maximum efficacy of 77.42%, slightly below the 88.51% efficacy attained by difenoconazole. Additional field trials are necessary to verify the protective and growth-promoting effects of these candidates, whether applied individually, combined in consortia, or integrated with chemical inputs in sugar beet crop production.

Carbapenem antibiotics are the drug of choice for treating multidrug-resistant bacterial infections. Metallo-beta-lactamases (MBLs) are carbapenemase capable of hydrolyzing nearly all therapeutically available beta-lactam antibiotics. Consequently, a need to assess the frequency and phenotypic resistance phenomena of two MBL genes in diarrheal and urinary tract infections (UTIs). Samples were collected through a cross-sectional study, with MBLs genes detected via PCR. Two hundred twenty eight diarrheal bacteria were isolated from 240 samples. The most predominant pathogens were Escherichia coli (32%) and Klebsiella spp. (7%). Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 50.4%, 65.6%, 66.8%, 80.5%, 54.4%, 41.6%, 25.7%, 41.2%, 37.2%, and 42.9%, respectively.  Total 142 UTI pathogens were obtained from 150 urine samples, with Klebsiella spp. (39%) and Escherichia coli (24%) are the major pathogens. Phenotypic resistance to amoxycillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 93.7%, 75.0%, 91.5%, 93.7%, 88.0%, 72.5%, 13.6%, 44.4%, 71.1%, and 43%, respectively.  Twenty four diarrheal isolates carried either blaNDM-1 or blaVIM genes; the overall MBL gene prevalence was 10.5%. Thirty six UTI pathogens carried either blaNDM-1 or blaVIM genes (25.4%). Seven isolates carried both blaNDM-1 and blaVIM genes.  MBL genes exhibited a strong association with phenotypic carbapenem and other beta-lactam antibiotic resistance. Resistance to carbapenems requires active surveillance and stewardship.

We changed the symmetry of the Weak Force from SU(2) to the quaternion group $Q_8$, and found that spin spacetime separates into two complementary spaces: a spin polarization spacetime of even parity states, and a spin coherence space, in the $S^3$ hypersphere, of odd parity coherent states. Under the quaternion group, spin is a boson of spin 1 in free flight and a fermion of spin $\frac{1}{2}$ when measured. It immediately follows that neutrinos are not needed to balance spin and conserve energy in beta decay. Additionally, we find the boson electrons emitted in beta decay are odd to parity, leading to parity conservation even though the observed beta distribution is asymmetrical.

The main objective of this paper is to introduce a further extension of extended (p, q)-beta function by considering two Mittag-Leffler function in the kernel. We investigate various properties of this newly defined beta function such as integral representations, summation formulas and Mellin transform. We define extended beta distribution and its mean, variance and moment generating function with the help of extension of beta function. Also, we establish an extension of extended (p, q)-hypergeometric and (p, q)-confluent hypergeometric functions by using the extension of beta function. Various properties of newly defined extended hypergeometric and confluent hypergeometric functions such as integral representations, Mellin transformations, differentiation formulas, transformation and summation formulas are investigated.

Objective: To examine the associations between menstruation features and symptoms and hormone-immune-metabolic biomarkers. Methods: Forty-one women completed questionnaires assessing characteristic menstruation symptoms, duration of menstrual cycle and number of pads used/day and completed the Daily Record of Severity of Problems (DRSP) during the consecutive days of their menstrual cycle. Menses-related symptoms (MsRS) were computed from the sum of 10 pre- and post-menses symptoms and the menstruation blood and duration index (MBDI) was computed based on the daily number of pads and duration of menses. We assayed serum levels of various biomarkers at days 7, 14, 21, and 28 of the subjects’ menstrual cycle. Results: MBDI was significantly associated with a) MsRS including low abdominal cramps, and gastro-intestinal (GI) and pain symptoms (positively); b) plasma levels of haptoglobin (Hp), CCL5, insulin growth factor (IGF)-1, and plasminogen activator inhibitor (PAI)1 (all positively); and c) estradiol and paraoxonase (PON)1 arylesterase activity (both inversely). MsRS were significantly predicted by CCL5 and IGF-1 (both positively) and progesterone (inversely). Low-abdominal cramps, and gastro-intestinal and pain symptoms were associated with lower progesterone levels. The MBDI+MsRS score was significantly predicted by the cumulative effects of (in descending order of importance): Hp, IGF-1, PON1 arylesterase, estradiol and PAI. Conclusion: Menstruation-related features including estimated blood loss, duration of menses, cramps, pain and GI symptoms are associated with hormone-immune-metabolic biomarkers, which mechanistically may explain those features. Women with an increased MBDI+MsRS index ≥ 0.666 percentile may be considered to have menstruation-related distress, including dysmenorrhea symptoms.

The stock beta coefficient literature extensively discusses the proper methods for the estimation of beta as well as its use in asset valuation. However, there are relatively few references with respect to the appropriate time horizon that investors should utilize when evaluating the risk-return relationship of a stock. We examine the appropriate time horizon for beta estimation differentiating our results by sector according to the Industry Classification Benchmark. We employ data from the NYSE and we estimate varying lengths of beta employing data from 30 to 250 trading days. The constructed beta series is then examined for the presence of breaks using the endogenous structural break literature. Results show evidence against the use of betas that employ more than 90 trading days of data provisional to the sector under study.

In this paper, we introduce a new class of open sets that is called is*-open set . Also, we present the notion of is*-continuous, is*-open, is*-irresolute, is*-totally continuous, and is-contra-continuous mappings, and we investigate some properties of these mappings. Furthermore, we introduce some is*-separation axioms, and is*-mappings are related with is*-separation axioms. . .

In the article, by applied the concept of strongly convex function and one known identity, we establish several Ostrowski type inequalities involving conformable fractional integrals. As applications, some new error estimations for the midpoint formula are provided as well.

We report on recent experimental results on β decay into self-conjugate (N=Z) nuclei with mass number 58≤A≤70. Super-allowed β decays from the Jπ=0+ ground state of a Z=N+2 parent nucleus are to the isobaric analogue state, through so-called Fermi transitions, and to Jπ=1+ states, by way of Gamow–Teller (GT) transitions. The operator of the latter decay is a generator of Wigner’s SU(4) algebra and as a consequence GT transitions obey selection rules associated with this symmetry. Since SU(4) is progressively broken with increasing A, mainly as a consequence of the spin–orbit interaction, this symmetry is not relevant for the nuclei considered here. We argue, however, that the pseudo-spin–orbit splitting can be small in nuclei with 58≤A≤70, in which case nuclear states exhibit an approximate pseudo-SU(4) symmetry. To test this conjecture, GT decay strength is calculated with use of a schematic Hamiltonian with pseudo-SU(4) symmetry. Some generic features of the GT β decay due to pseudo-SU(4) symmetry are pointed out. The experimentally observed GT strength indicates a restoration of pseudo-SU(4) symmetry for A=70.

Thalassemia is genetic blood disease cause by absence or decrease of one or more of the globin chain synthesis. Beta thalassemia is characterized by one or more mutations in beta globin gene. Absence or reduced amount the of beta globin chains cause ineffective erythropoiesis which leads to anemia. Beta thalassemia has been further divided into three main forms: Thalassemia minor/silent carrier, major and intermedia. More severe form is thalassemia major in which patients depend upon blood transfusion for survival and high level of iron occur as a consequence of consistent blood transfusion. Over loaded iron invokes the synthesis of reactive oxygen species that are toxic in redundancy and triggering the impairment to vascular, endocrine and hepatic system. Thalassemia can be diagnosed and detected through various laboratory tests such as blood smear, prenatal testing (genetic testing of amniotic fluid), DNA analysis (genetic testing) and complete blood count. Treatment of thalassemia intermedia is symptomatic but it can also be managed by splenectomy and folic supplementation. While thalassemia major can be treated by transplantation of bone marrow, regular transfusion of blood and iron chelation treatment, stimulation of fetal hemoglobin production, hematopoietic stem cell transplantation and gene therapy.

We proposed a so-called Beta Kumaraswamy Burr Type X distribution which gives the extension of the Kumaraswamy-G class of family distribution. Some properties of this proposed model were provided, like: the expansion of densi- ties and quantile function. We considered the Bayes and maximum likelihood methods to estimate the parameters and also simulate the model parameters to validate the methods based on dierent set of true values. Some real data sets were employed to show the usefulness and exibility of the model which serves as generalization to many sub-models in the elds of engineering, medical, survival and reliability analysis.

We proposed a so-called Beta Kumaraswamy Burr Type X distribution which gives the extension of the Kumaraswamy-G class of family distribution. Some properties of this proposed model were provided, like: the expansion of densities and quantile function. We considered the Bayes and maximum likelihood methods to estimate the parameters and also simulate the model parameters to validate the methods based on different set of true values. Some real data sets were employed to show the usefulness and flexibility of the model which serves as generalization to many sub-models in the field of engineering, medical, survival and reliability analysis.

A new generalization of extended beta function and its various properties, integral representations and distribution are given in this paper. In addition, we establish the generalization of extended hypergeometric and con uent hypergeometric functions using the newly extended beta function. The properties these extended and con uent hypergeometric functions such as integral representations, Mellin transformations, dif- ferentiation formulas, transformation and summation formulas are also investigated.

Optical conductivity of an interacting polaron gas is calculated within an extended random phase approximation which takes into account mixing of collective excitations of the electron gas with LO phonons. This mixing is important for the optical response of strongly polar crystals where the static dielectric constant is rather high, as in the case of strontium titanate. The present calculation sheds light on unexplained features of experimentally observed optical conductivity spectra in $n$-doped SrTiO$_{3}$. These features appear to be due to dynamic screening of the electron-electron interaction by polar optical phonons and hence do not require additional mechanisms for their explanation.

With reference to Planck scale, Mach’s relation, increasing support for large scale cosmic anisotropy and preferred directions and by introducing two new parameters Gamma and Beta, right from the beginning of Planck scale, we make an attempt to estimate ordinary matter density ratio, dark matter density ratio, mass, radius, temperature, age and expansion velocity (from and about the baby universe in all directions). We would like suggest that, from the beginning of Planck scale, 1) Dark matter can be considered as a kind of cosmic foam responsible for formation of galaxies. 2) Cosmic angular velocity is directly proportional to squared cosmic temperature. 3) Ratio of critical temperature to actual temperature plays a heuristic role in understanding ordinary and dark matter density ratios. 4) Cosmic expansion velocity increases with decreasing total matter density ratio. 5) There is no need to consider dark energy for understanding cosmic acceleration.

In this paper we introduce the concept of Nano Beta Closure, Nano Beta Interior and study the relationship between them also study some of their properties. Based on these notions we introduced the topological Approach to Decision Making and Its Application in the Medical Field" which describes the use of topological methods in decision-making, specifically through the utilization of nano beta closure and nano beta interior. These mathematical tools are applied in the medical field to improve diagnostic accuracy and aid in treatment planning. The authors demonstrate the effectiveness of this approach through a case study on the diagnosis of Chronic Kidney. The results show that the topological approach using nano beta closure and nano beta interior provides a reliable and accurate method for medical decision-making. Finally, we introduce a medical application for disease groups patients of with chronic kidney. To identify the main causative agent of kidney disease. where using this approach, the medical team can identify the specific areas of the kidney that are affected by the infection, as well as the extent of damage and any potential complications. This information is used to create an individualized treatment strategy that is customized to meet the specific requirements of the patient. and medical history. We write an algorithm that can be a helpful tool for doctors to utilize in diagnosing infection disease Chronic Kidney infections. By utilizing this approach, clinicians can provide accurate diagnoses, develop effective treatment plans, and ultimately improve patient outcomes. finally, we show that fractals hold significant importance in future nano topological generation of the human factor. Their unique properties and self-similar patterns offer insights into the complex organization of biological systems and provide a foundation for designing advanced Nanosystems.

The novel coronavirus pneumonia (COVID-19) is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a novel virus of the coronavirus family, SARSCoV-2. A recent pre-print study has showed a heme attack on the 1-beta chain of hemoglobin by COVID19. Beta-thalassemia results of a default in the hemoglobin beta- chain synthesis. 1,5% global population are heterozygotes for this disease. In this study, by a multiple linear regression, we have analyzed the evolution of COVID-19 infection in three Italian regions (Puglia, Sardinia, Sicilia) with different beta-thalassemic prevalences, in order to search a link. The results have showed that betathalassemic heterozygote population prevalence is correlated to immunity against COVID-19, by a regression. This paper is only for academic discussion, the hypotheses and conclusions needs to be confirmed by further research .

In this study, we aim to evaluate how cyclodextrin molecules affect the hydrophilicity and selec-tivity of PVDF membrane. Herein, we prepared PVDF-PVP(1-x) β-CDx membranes, with x rang-ing from 0 to 1 wt%. The membranes were deeply characterized by means of X-ray diffraction (XRD), attenuated total reflectance infrared (ATR-IR), Raman spectroscopies, Thermal gravimet-ric analysis (TGA), Contact angle measurement (CA), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The study unequivocally demonstrates the effectiveness of the addition of β-CD molecules on membranes' structural, morphological, and dielectric properties. Adding 0.25wt% β-CD enhanced hydrophilicity, with CA decreasing from 72.6° to 56° and roughness decreasing from 81 to 29 nm. The PVDF-PVP(1-x) β-CDx membranes were then fully characterized using electrochemical impedance spectroscopy (EIS) to determine their dielectric properties, which clearly showed that the presence of β-CD induced polarization of the mem-brane. The separation of various dyes with different sizes and charges was utilized. These dyes included methylene blue (MB, positive, 0.504 nm), methyl red (MR, neutral, 0.487 nm), rose Bengal (RB, negative, 0.588 nm), and brilliant blue (BB, negative, 0.798 nm). Based on our re-search, we found that the membrane's selectivity is determined by both exclusion factors (such as size and dielectric properties) and inclusion inside the β-CD cage. We found that using alpha-CD instead of beta-CD led to the disappearance of dye inclusion. These findings strongly sug-gest that β-CD molecules can be a viable solution for dye removal from wastewater.

We consider a specific holographic model in the limit where the gauge field does not couple to the rest of of the holographic fields (gravity and scalar sector) and investigate a phase of matter at zero charge density, a realistic feature that may have implications for disordered strange metals. We then pick a specific form of the gauge coupling $Z(\alpha)$ with a certain disorder realization and argue that this provides a hard-gapped insulator with exponentially-suppressed conductivity by holographic methods. The limit is non-trivial: as there is backreaction at zero density amount, surviving in the coupled case.

Several specific types of generalized maps of a generalized topological space have been defined and investigated for various purposes from time to time in the literature of topological spaces. Our recent research in the field of a new class of generalized maps of a generalized topological space is reported herein as a starting point for more generalized classes.

Potassium inwardly-rectifying channel, subfamily J, member 12 (KCNJ12) gene is one promising candidate for economic traits because of its crucial roles in myoblast development. Here, a missense mutation (Cys>Arg), was firstly detected to locate in exon 3 of KCNJ12 from three Chinese cattle breeds by DNA-pool sequencing. Then, we performed the association analysis of this SNP with stature in three Chinese cattle populations (n = 820). Significantly positive correlation was revealed by reduced animal general linear model and the genotype of CC is the most excellent genotype in three breeds. Further, we measured the expression profiling of the KCNJ12 gene in various cattle tissues and primary bovine skeletal muscle cells. Ubiquitous expression with high abundance in muscle was observed. Further, in primary bovine skeletal muscle cells, the KCNJ12 mRNA expression was gradually up-regulated in differentiation medium (DM) compared with that in growth medium (GM), suggesting that KCNJ12 gene is involved in bovine myocyte differentiation. Conclusively, KCNJ12 gene is a functional candidate gene which can be used as molecular marker for beef cattle breeding.

The apparent metal-insulator transition (MIT) in two-dimension (2D) was discovered by Kravchenko et al. [1] more than two decades ago in strongly interacting 2D electrons residing in a Si-metal-oxide-semiconductor field-effect transistor (Si-MOSFET). Its origin remains unresolved. Recently, low magnetic field reentrant insulating phases (RIPs), which dwell between the zero-field (B=0) metallic state and the integer quantum Hall (QH) states where the Landau-level filling factor υ > 1, have been observed in strongly correlated 2D GaAs hole systems with large interaction parameter rs (~20-40) and high purity. A new complex phase diagram was proposed, which includes zero field MIT, low magnetic field RIPs, integer QH states, fractional QH states, high field RIPs and insulating phases (HFIPs) with υ < 1 in which the insulating phases are explained by the formation of Wigner crystal. Furthermore, evidences of new intermediate phases were reported. All contribute to the further understandings of the puzzle. This review article serves the purpose of summarizing those recent experimental findings and theoretical endeavors, to foster future research efforts.

Using the method of the beta function, Sun has recently evaluated some series of the type $\sum_{k=0}^{\infty}(ak+b)x^k/\binom{mk}{nk}$. By factorization of the polynomial $t^{m-n}(1-t)^n-x$, we will give a general method to find new $\pi$-series.

This paper introduces a novel ensemble adjustment Kalman filter (EAKF) that integrates a machine-learning approach. The approach employs nonlinear variable relationships established by a deep neural network (DNN) during the analysis stage of the EAKF. This process nonlinearly projects observation increments into the state variable space. The newly developed DNN-EAKF algorithm can be applied to coupled data assimilation using coupled ocean-atmosphere models. It enhances cross-component updates in strongly coupled data assimilation (SCDA) by diminishing errors in estimating cross-component error covariance arising from insufficient ensemble members, thereby improving the SCDA analysis. This paper employs a conceptual model to conduct twin experiments, validating the DNN-EAKF’s capability to utilize cross-component observation information in SCDA effectively. The approach is anticipated to offer insights for future methodological integrations of machine learning and data assimilation and provide methods for SCDA applications in coupled general circulation models.

Truffles contribute to crucial dynamics in the soil systems, being involved in plentiful ecological functions important for ecosystems. Despite this, the interactions between truffles and surrounding mycobiota remain unknown. Here, we aimed to shed light on how much truffle species could affect its surrounding soil mycobiota. Using traditional chemical analysis and Illumina ITS amplicon sequencing, we compared soil nutrients and mycobiota surrounding two truffle species: Tuber indicum (Ti) and T. pseudohimalayense (Tp) inhabit in the same Pinus armandii forest in southwestern China. Tp soil was more acidic and had higher nutrients (total C, N, P contents) than Ti soil. Fungal richness and diversity of truffle ascomata and surrounding soils were significantly higher in Tp than in Ti. Redundancy analysis showed relationships between soil fungal taxa and soil properties had changed from negative (Tp) to positive (Ti) and shifted from a moisture-driving (Tp) to a total N-driving (Ti). Overall, our results showed that the interactions between truffle and soil system had been altered with species variation, although the causative peculiarity of these associations needs to be further studied.

A precise understanding of the genes and associated genomes of SARS-CoV2 is important for various reasons such as discovering origin of the virus and virulence and so on. A thorough descriptive understanding of the SARS-CoV2 genomes and other coronavirus of the beta-coronavirus genus is primarily important. In this article, a set of ten genomes of four CoVs and their associated genes are considered for this present study. A spatial representations of nucleotide bases including purine-pyrimidine representations of the different genes of the corresponding genomes are quantified using Hurst exponent, Shannon entropy and density estimation of different nucleotides including GC content, in order to draw a comparison and contrast among the ten genomes of different types of CoVs which include MERS, SARS-CoV, HKU1 (Human Coronavirus) and associated their genes.

Bergamot flavonoids have been shown to prevent metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and stimulate autophagy in animal models and patients. To investigate further the mechanism of polyphenol-dependent effects, we performed RT2-PCR array analysis on 168 metabolism, transport and autophagy-related genes expressed in rat livers exposed for 14 weeks to different diets: standard, cafeteria (CAF) and CAF diet supplemented with 50 mg/kg of Bergamot Polyphenol Fraction (BPF). CAF diet caused a strong upregulation of the gluconeogenesis pathway (Gck, Pck2) and a moderate (>1.7 fold) induction of genes regulating lipogenesis (Srebf1, Pparg, Xbp1), lipid and cholesterol transport or lipolysis (Fabp3, Apoa1, Lpl) and inflammation (Il6). However, only one -oxidation gene (Cpt1a) and a few autophagy genes were modulated in the CAF group compared to controls. While most of these transcripts were significantly modulated by BPF, we observed a particularly potent effect on lipogenesis genes, like Acly, Acaca, Fasn and Scd1, which were suppressed far below the mRNA levels of control livers as confirmed by alternative primers-based RT2-PCR analysis and western blotting. These effects were accompanied by downregulation of pro-inflammatory cytokines (Il6, Tnfa, and Il10) and diabetes-related genes. Few autophagy (Map1Lc3a, Dapk) and no -oxidation gene expression changes were observed, suggesting minor transcriptional effects on autophagy. In conclusion, chronic BPF supplementation efficiently prevents NAFLD by modulating hepatic energy metabolism and inflammation gene expression programs, with no effect on -oxidation, but profound suppression of de-novo lipogenesis.

This review was carried out to identify different beta-lactamase resistance genes reported in published literature from Nigeria and to determine the proportion estimates of the important beta-lactamase resistance genes in Nigeria. Sixty-three (63) articles were included in this review based on the eligibility criteria. All the beta-lactamases reported were detected from the Gram-negative bacteria, most especially from Enterobacteriaceae (n=53). Thirty-six different beta-lactamase genes have been reported from Nigeria. These genes belong to the narrow-spectrum, AmpC, extended-spectrum, and carbapenemase beta-lactamase resistance genes. Eight (8) genes (bla_DHA, bla_CTXM-1, bla_CTXM-14, bla_GES-1, bla_VEB-1, bla_OXA-1, bla_OXA-2, and bla_TEM-1) were shared between animals and humans, 5 genes (bla_SHV-1, bla_SHV-2, bla_SHV-11, bla_SHV-12, and bla_NDM-1) were common to both humans and environment while none of the genes was unique to both animals and environment. Four genes including bla_CMY, bla_TEM-1, bla_AmpC, and internationally pandemic bla_CTXM-15 gene were unique to animals, humans, and the environment. No carbapenemase gene was reported from animals yet. The pooled proportion estimate of ESBL genes in Nigeria was 31% (95% CI: 26-36%, P<0.0001), while the estimate of bla_CTXM-15 gene in Nigeria was 46% (95% CI: 36-57%, P<0.0001). The proportion estimate of AmpC genes was 32% (95% CI: 11-52%, P<0.001), while the estimate for carbapenemases was 8% (95% CI: 5-12%, P<0.001). This study has provided information on the beta-lactamases distribution in Nigeria. This is necessary for a better understanding of molecular epidemiology of clinically important beta-lactamases especially the extended-spectrum beta-lactamases and carbapenemases in Nigeria.

Introduction: This study aims to elucidate the clinical diagnostic value of S100 Calcium Binding Protein beta (S100B) in epilepsy, a topic of ongoing debate among European and Asian epilepsy research centres.Methods and analysis: A structured long-term research plan was developed, comprising three phases. Phase one involves observational studies investigating the correlation between S100B levels in serum or cerebrospinal fluid and epilepsy. Phase two integrates observational and randomised controlled data to establish baseline S100B levels across diverse epilepsy demographics, underpinning the predictive value of S100B for epilepsy. Phase three focuses on randomised controlled trials to evaluate the diagnostic accuracy of S100B as an epilepsy biomarker.Ethics and dissemination: All enrolled patients will provide written consent. The ethics committee of the Second People’s Hospital of Gansu Province, Affiliated Hospital of Northwest Minzu University, China, approved the study (GSSEY2022-KY009-01).Registration: The study is registered with PROSPERO (CRD42023425431).

Vaccination is one of the most effective methods for preventing morbidity and mortality from COVID-19. Vaccine hesitancy has led to a decrease in vaccine uptake; driven by misinformation, fear, and perceptions of vaccine safety. Whole inactivated vaccines have been used in one-fifth of the vaccine recipients in Africa, however there is limited real-world data on their safety. We evaluated the reported side effects and factors associated with reported side effects following vaccination with whole inactivated COVID-19 vaccines - BBiBP-CorV (Sinopharm) and CoronaVac (Sinovac). A quantitative survey evaluating attitudes and side effects from vaccination was administered to 1016 adults presenting at vaccination centers. Two follow-up telephone interviews were conducted to determine side effects after the first and second vaccination dose. Overall, the vaccine was well tolerated; 26.0% and 14.4% reported side effects after the first and second dose respectively. The most frequent local and systemic side effects were pain at the injection site and headaches respectively. Most symptoms were mild, and no participants re-quired hospitalization. Participants who perceived COVID-19 vaccines as safe or had a personal COVID-19 experience were significantly less likely to report side effects. Our findings provide data on the safety and tolerability of whole inactivated COVID-19 vaccines in an African population, providing the necessary data to create effective strategies to increase vaccination and support vaccination campaigns.

Studies on crop response to light quality [red (R) to far-red (FR) light ratio] often recommend early weed removal to reduce the effects of shade avoidance responses on crop yield. However, it is unclear whether crops are able to distinguish reflected light quality of kin from that of non-kin. We evaluated the response of sugarbeet (Beta vulgaris L.) to reflected FR light from sugarbeet, common lambsquarters (Chenopodium album L.), Kentucky bluegrass (Poa pratensis L.), alfalfa (Medicago sativa L.), and bare soil (control) under outdoor conditions in 2016 and 2017. Treatments were completely randomized with 10 replications per treatment. The study methods ensured there was no direct resource competition. The reflected R:FR of plant species ranged from 0.06 (common lambsquarters) to 0.24 (sugarbeet) compared to 0.7 for the bare soil. In both 2016 and 2017, there were 2 to 4 more leaves in the sugarbeet surrounded by soil compared to sugarbeet surrounded by neighboring species. There was up to 47, 57, 43, and 23% reduction in sugarbeet leaf area, shoot dry weight, root diameter, and root dry weight, respectively, due to reflected R:FR light from neighboring species. Sugarbeet did not respond differently to reflected light quality of kin compared to non-kin.

In a previous paper we defined the Black-and-White SAT problem which has exactly two solutions, where each variable is either true or false. We showed that Black-and-White $2$-SAT problems represent strongly connected directed graphs. We presented also the strong model of communication graphs. In this work we introduce two new models, the weak model, and the Balatonbogl\'{a}r model of communication graphs. A communication graph is a directed graph, where no self loops are allowed. In this work we show that the weak model of a strongly connected communication graph is a Black-and-White SAT problem. We prove a powerful theorem, the so called Transitions Theorem. This theorem states that for any model which is between the strong and the weak model, we have that this model represents strongly connected communication graphs as Blask-and-White SAT problems. We show that the Balatonbogl\'{a}r model is between the strong and the weak model, and it generates $3$-SAT problems, so the Balatonbogl\'{a}r model represents strongly connected communication graphs as Black-and-White $3$-SAT problems. Our motivation to study these models is the following: The strong model generates a $2$-SAT problem from the input directed graph, so it does not give us a deep insight how to convert a general SAT problem into a directed graph. The weak model generates huge models, because it represents all cycles, even non-simple cycles, of the input directed graph. We need something between them to gain more experience. From the Balatonbogl\'{a}r model we learned that it is enough to have a subset of a clause, which represents a cycle in the weak model, to make the Balatonbogl\'{a}r model more compact. We still do not know how to represent a SAT problem as a directed graph, but this work gives a strong link between two prominent fields of formal methods: SAT problem and directed graphs.

In this paper, a kind of single-walled carbon nanotube nonlinear model is developed, and the strongly nonlinear dynamic characteristics of such carbon nanotubes subjected to random magnetic field are studied. The nonlocal effect of microstructure is considered based on the theory of nonlocal elasticity. The natural frequency of the strongly nonlinear dynamic system is obtained by the energy function method, the drift coefficient and the diffusion coefficient are verified. The stationary probability density function of the system dynamic response is given and the fractal boundary of the safe basin is provided. Theoretical analysis and numerical simulation show that stochastic resonance occurs when varying the random magnetic field intensity. The boundary of safe basin has fractal characteristics and the area of safe basin decreases when the intensity of the magnetic field permeability increases.

Crustacean hyaluronidases are 1 poorly understood both in terms of their enzymatic properties and in terms of their structural features. In this work, we have shown that the hepatopancreas homogenate of the red king crab has a hyaluronidase activity that is an order of magnitude higher than its commercial counterpart. Zymography revealed the hyaluronidase activity of the protein roughly from40 to 50 kDa relative to the molecular marker used in electrophoresis. Analysis of the hepatopancreas transcriptome revealed a hyaluronidase sequence with an expected molecular weight of 42.5 kDa. It turned out that the reaction of cleavage of hyaluronate in the presence of a homogenate proceeds by the mechanism of b-elimination, which is well known for bacterial hyaluronidases. Thus, a new hyaluronidase of higher eukaryotes was found and described, which is not integrated into the modern classification of hyaluronidases.

We experimentally demonstrate enhanced self-phase modulation (SPM) in silicon nitride (Si₃N₄) waveguides integrated with 2D graphene oxide (GO) films. GO films are integrated onto Si₃N₄ waveguides using a solution-based, transfer-free coating method that enables precise control of the film thickness. Detailed SPM measurements are carried out using both picosecond and femtosecond optical pulses. Owing to the high Kerr nonlinearity of GO, the hybrid waveguides show significantly improved spectral broadening compared to the uncoated waveguide, achieving a broadening factor of up to ~3.4 for a device with 2 layers of GO. By fitting the experimental results with theory, we obtain an improvement in the waveguide nonlinear parameter by a factor of up to 18.4 and a Kerr coefficient (n₂) of GO that is about 5 orders of magnitude higher than Si₃N₄. Finally, we provide a theoretical analysis for the influence of GO film length, coating position, and its saturable absorption on the SPM performance. These results verify the effectiveness of on-chip integrating 2D GO films to enhance the nonlinear optical performance of Si₃N₄ devices.

We study strong optical coupling of metal nanoparticle arrays with dielectric substrates. Based on the Fermi Golden Rule, the particle-substrate coupling is derived in terms of the photon absorption probability assuming a local dipole field. An increase in photocurrent gain is achieved through the optical coupling. In addition, we describe light-induced, mesoscopic electron dynamics via the nonlocal hydrodynamic theory of charges. At small nanoparticle size (<20nm), the impact of this type of spatial dispersion becomes sizable. Both absorption and scattering cross section of the nanoparticle are significantly increased through the contribution of additional nonlocal modes. We observe a splitting of local optical modes spanning several tenths of nanometers. This is a signature of semi-classical, strong optical coupling via the dynamic Stark effect, known as Autler-Townes splitting. The photocurrent generated in this description is increased by up to 2%, which agrees better with recent experiments than compared to identical classical setups with up to 6%. Both, the expressions derived for the particle-substrate coupling and the additional hydrodynamic equation for electrons are integrated into COMSOL for our simulations.

A subset of patients with schizophrenia experience physio-somatic symptoms reminiscent of chronic fatigue and fibromyalgia. In schizophrenia, these symptoms contribute to impaired quality of life, and are strongly related to neuro-cognitive deficits, and increased IgA responses to tryptophan catabolites. Negative and PHEM (psychosis, hostility, excitation, mannerism) symptoms, psychomotor retardation (PMR) and formal thought disorders, appear to be manifestations of a single trait reflecting overall severity of schizophrenia (OSOS). In this study, 120 patients with deficit schizophrenia (DEFSCZ) and 54 healthy subjects were assessed with the FibroFatigue (FF) rating scale, and the above-mentioned symptom domains as well as neuro-cognitive tests and biomarkers were measured. In DEFSCZ, there were robust associations between the FF score and all above-mentioned symptom domains, and impairments in semantic and episodic memory and executive functions. Furthermore, the FF score loaded highly on an OSOS latent vector (LV), which showed adequate convergent validity, internal consistency reliability and predictive relevance and fitted a reflective model. Soft Independent Modelling of Class Analogy (SIMCA) showed that the FF items discriminated DEFSCZ from controls with an overall accuracy of 100%. Interleukin IL-1β, IL-1 receptor antagonist (sIL-1RA), tumour necrosis factor (TNF)-α and CCL-11 (eotaxin) explained 66.8% of the variance in the FF score and 59.4% of the variance in OSOS. In conclusion, these data show that physio-somatic symptoms are a core component of the phenomenology of DEFSCZ and are largely mediated by neurotoxic effects of activated immune pathways, including aberrations in CCL-11, IL-1β and TNF-α signalling.

(1) Background: Angiotensin II, a major culprit in cardiovascular disease, activates mediators that are also involved in pathological cardiac remodelling. We aimed at investigating the effects of two of them: aldosterone (Ald) and transforming growth factor-beta-1 (TGF-β1 ), on cardiac remodelling in an in vivo model. (2) Methods: Six-week-old male wild-type (WT) and TGF-β1 -overexpressing transgenic (TGF-β1 -TG) mice were infused with subhypertensive doses of Ald for 2 weeks, and/or treated orally with eplerenone from postnatal day 21. Heart’s ventricles were examined: by morphometry, immunoblotting to assess intracellular signalling pathways, RT qPCR to determine hypertrophy and fibrosis marker genes. (3) Results: TGF-β1 -TG mice spontaneously developed cardiac hypertrophy and interstitial fibrosis, exhibited higher baseline phosphorylation of p44/42 and p38 kinases, fibronectin and ANP mRNA expression. Ald induced a comparable increase in ventricular heart weight-to-body-weight ratio and cardiomyocyte diameter in both strains, but less pronounced increase in interstitial fibrosis in transgenic compared to WT mice (23.6% vs 80.9%, p&lt;0.005). Ald increased phosphorylation of p44/42 and p38 in WT but not TGF-β1 -TG mice. While eplerenone-enriched chow partially prevented Ald-induced cardiac hypertrophy in both genotypes and interstitial fibrosis in WT controls, it completely protected from additional fibrosis in transgenic mice. (4) Conclusions: Ald appears to induce cardiac hypertrophy independently of TGF-β1 , while in case of fibrosis downstream signalling pathways of these two factors probably converge

Pancreatic beta cells secrete insulin in response to stimulation with glucose and other nutrients, and impaired insulin secretion plays a central role in development of diabetes mellitus. Pharmacological management of diabetes includes various antidiabetic drugs, including incretins. The incretin hormones, glucagon-like peptide-1 and gastric inhibitory polypeptide, potentiate glucose-stimulated insulin secretion by binding to G protein-coupled receptors, resulting in stimulation of adenylate cyclase and production of the secondary messenger cAMP, which exerts its intracellular effects through activation of protein kinase A or the guanine nucleotide exchange protein 2A. The mo-lecular mechanisms behind these two downstream signaling arms are still not fully elucidated and involve many steps in the stimulus-secretion coupling cascade, ranging from the proximal regula-tion of ion channel activity, to the central Ca2+ signal, and the most distal exocytosis. In addition to modifying intracellular coupling, the effect of cAMP on insulin secretion could also be at least partly explained by the impact on intercellular coupling. In this review, we systematically describe the possible roles of cAMP at these intra- and inter-cellular signaling nodes, keeping in mind the rele-vance for the whole organism and translation to humans.

Iloperidone (ILO) is a second-generation antipsychotic drug and a first-line treatment approved by USFDA in May 2009. Iloperidone belongs to Biopharmaceutical Classification Systems (BCS) class II; thus, it is poorly water-soluble, highly permeable, and has pH-dependent solubility. Cyclodextrins and their derivatives have a wide range of applications in different formulations due to their complexation ability, which improves the solubility, stability, safety, and bioavailability of a drug. We have tried the complexation of iloperidone with sulfobutyl ether-β-cyclodextrin (SEβCD) to improve its solubility and dissolution. Complexation was done by the kneading method. The characterization of the SEβCD complexes with Iloperidone was done by FTIR, differential scanning calorimetry (DSC), saturation solubility, etc. A multimedia dissolution of the complex was carried out and compared with the plain drug. A significant improvement in drug release was found from SEβCD complexes in all media when compared with the drug alone.

Background: The antimalarial drug chloroquine and antimicrobial drug azithromycin have received significant attention during the current COVID-19 pandemic. Both drugs can alter cardiac electrophysiology and have been associated with drug-induced arrhythmias. Meanwhile, sympathetic activation is commonly observed during systemic inflammation and oxidative stress (e.g., in SARS-CoV-2 infection), and may influence the electrophysiological effects of chloroquine and azithromycin. Here, we investigated the effect of beta-adrenergic stimulation on proarrhythmic properties of chloroquine and azithromycin using a detailed in silico model of ventricular electrophysiology. Methods: Concentration-dependent chloroquine and azithromycin-induced alterations in ion-channel function were incorporated into the Heijman canine ventricular cardiomyocyte model. Single and combined drug effects on action-potential (AP) properties were analyzed using a population of 592 models accommodating inter-individual variability. Sympathetic stimulation was simulated by an increase in pacing rate and experimentally validated isoproterenol-induced changes in ion-channel function. Results: At 1 Hz pacing, therapeutic doses of chloroquine and azithromycin (5 and 20 µM, respectively) individually prolonged AP duration (APD) by 33% and 13%. Their combination produced synergistic APD prolongation (+161%) with incidence of proarrhythmic early afterdepolarizations in 53.5% of models. Increasing the pacing frequency to 2 Hz shortened APD and together with 1 µM isoproterenol corrected the drug-induced APD prolongation. No afterdepolarizations occurred following increased rate and simulated application of 0.1-1 µM isoproterenol. Conclusion: Sympathetic stimulation limits chloroquine- and azithromycin-induced proarrhythmia by reducing their APD-prolonging effect, suggesting the importance of heart rate and autonomic status monitoring in particular conditions (e.g., COVID-19).

While vaccines are a well-established method of controlling the spread of infectious diseases, vaccine hesitancy jeopardizes curbing the spread of COVID-19. Through the Vaccine Information Network (VIN), this study explored barriers and motivators to COVID-19 vaccine uptake. We conducted 18 focus group discussions with male and female community members, stratified by country, age group, and—for Zimbabwe only—by HIV status. Participants’ median age across both countries was 40 years (interquartile range of 22–40) and most (65.9%) were female. We conceptualized the key themes within the World Health Organization’s Strategic Advisory Group of Experts on Immunization (SAGE) 3Cs (convenience, confidence, complacency) vaccine hesitancy model. Barriers to vaccine uptake—lack of convenience, low confidence, and high complacency—included inaccessibility of vaccines and vaccination sites, vaccine safety and development concerns, and disbelief in COVID-19’s existence. Motivators to vaccine uptake—convenience, confidence and low complacency—included accessibility of vaccination sites, user-friendly registration processes, trust in governments and vaccines, fear of dying from COVID-19 and knowing someone who had died or become infected with COVID-19. Overall, vaccine hesitancy in South Africa and Zimbabwe was influenced by inconvenience, a lack of confidence, and high complacency around COVID-19 vaccines.

In recent years, there has been a growing interest in the preoperative modeling of fluid-structure interaction in the treatment of cerebral aneurysms. In this study, we investigate two cases involving laminar incompressible fluid flow interacting with hyperelastic materials (a vertical flap and aneurysm walls) under the effect of fluid flow. We present a finite element method (FEM) for these prototypical two-dimensional ($2D$) configurations, taking into account the complex flows and deformation of the variant's structure models. We use an Arbitrary Lagrangian-Eulerian (ALE) formulation in a continuum, fully monolithic coupled way, and discretize the fluid and solid domains using the quadratic LBB stable $P_2P_1$ finite element pair to approximate the displacement, velocity, and pressure spaces independently. The resulting discretized form of the nonlinear algebraic system is linearized using a variant of Newton's procedure, and the Jacobian matrices are approximated via the divided difference method. The resulting linear systems are solved using a direct solver MUMPS. We evaluate hydrodynamic forces such as drag and lift coefficients for nonlinear elastic material models, including Saint-Venant Kirchoff, Neo-Hookean, and Mooney-Rivlin (2 parameters) separately. To gain more physical insight into the problem, we verify the computed results by comparing the velocity, viscosity, and pressure fields. Our aim is to qualitatively analyze the changes in the mechanics of the wall behavior of the elasticity of the flap vs. the complexity of deformation, interface, details for prototypical flow situations, corresponding displacement, and deformation. We also provide a physical interpretation of blood flow magnitude and basic hemodynamic phenomena of wall shear stresses (WSS) in aneurysma and the range of deformation. Overall, this study presents a comprehensive approach to modeling fluid-structure interaction in cerebral aneurysms, which could help in the development of more effective treatment strategies.

The neutrino is perhaps the most elusive member of the particle zoo. The questions about its nature, namely: Dirac or Majorana, the value of its mass and the interactions with other particles, the number of its components including sterile species, are long standing ones and still re- main in large extent without conclusive answers. From the side of the nuclear structure and nuclear reactions, both theories and experiments, the need to elucidate these questions have, and still has, prompt crucial developments in the fields of double beta decay, double charge exchange and neutrino induced reactions. The measurements of neutrino flavor os- cillation parameters contribute largely to restrict models with massless neutrinos. From the particle physics side, the possibilities to extent the standard model of electroweak interactions to incorporate a right handed sector of the electroweak lagrangian are directly linked to the adopted neu- trino model. Here, I would like to address another aspect of the problem by asking the question of the neutrino mass mechanism in the cosmological context, and particularly about dark matter.

Searching for neutrinoless double beta decay is a top priority in particle and astroparticle physics, being the most sensitive test of lepton number violation and the only suitable process to probe the Majorana nature of neutrinos. In order to increase the experimental sensitivity for this particular search, ton-scale detectors operated at nearly zero-background conditions with a few keV energy resolution are required. In this scenario, cryogenic detectors have proven effective in addressing many of these issues simultaneously. After long technical developments, the CUORE experiment established the possibility to operate large scale detectors based on this technology. Parallel studies pointed out that scintillating cryogenic detectors represent a suitable upgrade for the CUORE design, directed towards higher sensitivities. In this work, we review the recent development of cryogenic detectors, starting from the status of the art and outlying the path toward next-generation experiments.

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders. In order to replace the function of the destroyed pancreatic beta cells in diabetes, islet transplantation is the widely practiced treatment; however, it has several limitations. As an alternative approach, human pluripotent stem cells (hPSCs) can provide an unlimited source of pancreatic cells that have the ability to secrete insulin in response to high blood glucose level. However, determination of the appropriate pancreatic lineage candidate for the purpose of cell therapy for treatment of diabetes is still debated upon. While hPSC-derived beta cells are perceived as the ultimate candidate, the efficiency needs further improvement in order to obtain a sufficient number of glucose responsive β-cells for transplantation therapy. On the other hand, hPSC-derived pancreatic progenitors can be efficiently generated in vitro and can further mature into glucose responsive beta cells in vivo after transplantation. Herein, we discuss the advantages and predicted challenges associated with the use of each of the two pancreatic lineage products for diabetes cell therapy. Furthermore, we address co-generation of functionally relevant islet cell subpopulations and structural properties contributing to glucose responsiveness of beta cells, as well as the available encapsulation technology for these cells.

Alveolar Rhabdomyosarcoma (ARMS), an invasive subtype of Rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic fusion genes PAX3-FOXO1 or PAX7-FOXO1. ARMS patients exhibit an overexpression of the pleiotropic cytokine Transforming growth factor beta (TGF-β). This overexpression of TGF-β1 causes an increased expression of a downstream transcription factor called SNAIL, which promotes Epithelial to Mesenchymal Transition (EMT). Overexpression of TGF-β also inhibits myogenic differentiation, making ARMS patients highly resistant to chemotherapy. In this review, we first describe different types of RMS and then focus on ARMS and the impact of TGF-β in this tumor type. We next highlight current chemotherapy strategies including a combination of FDA approved drugs vincristine, actinomycin D, and cyclophosphamide (VAC), Cabozantinib, Bortezomib, Vinorelbine, AZD 1775 and cisplatin. Lastly, we discuss chemotherapy agents that target the differentiation of tumor cells in ARMS which include all trans retinoic acid (ATRA) and 5-Azacytidine. Improving our understanding of the role of signaling pathways, such as TGF-β1, in the development of ARMS tumor cells differentiation will help inform more tailored drug administration in the future.

There is clinical concern about the combined use of alcohol and opiates. Several lines of evidence support an interaction between alcohol and the endogenous opioid system. Thus, we hypothesized that ethanol by causing the release of opioid peptides may sensitize the system to the action of exogenous opioids such as morphine. In this study, using the place conditioning paradigm as an animal model of reward, we determined whether a morphine challenge would alter the pre-established preference induced by ethanol conditioning in mice, and whether this response was mediated by the mu opioid receptor (MOP). Given that ethanol exposure stimulates the release of opioid peptides, we also assessed the role of beta-endorphin (β-END) and enkephalins (ENKs) in this response. Mice lacking MOP, β-END and/ or ENKs as well as their respective wild-type controls were tested for baseline place preference on day 1, conditioned with ethanol (2 g/kg) versus saline on days 2 to 4 and then tested under a drug-free state for postconditioning place preference on day 5. On day 8, mice received a single injection of morphine (5 mg/kg) and were tested for place preference. On each test day, mice were placed in the central neutral chamber and allowed to freely explore the conditioning chambers. The amount of time that mice spent in each chamber was recorded. We found that a challenge dose of morphine given on day 8 enhanced the CPP response in mice previously conditioned with ethanol. This response was abolished in MOP null mice, confirming the role of MOP in this response. Although this enhanced response was not altered in mice lacking either β-end or ENKs compared to their wild-type littermates/controls, it was completely blunted in mice lacking both β-end and enkephalins. Together, these results suggest that these opioid peptides jointly mediate the crosstalk between the rewarding actions of morphine and ethanol.

We propose that the coexistence of gapless Fermi arcs with the metal-insulator crossover of in-plane resistivity in strongly underdoped cuprates can be explained by the FL* fractionalized Fermi liquid nature of these systems and it is not due simply to disorder effects. The particle excitations of this FL* system derived from variants of the t-J model are: the gapless holon carrying charge with small Fermi momentum proportional to the doping, the gapful spinon carrying spin 1/2, gauge fluctuations coupling them and the hole as a spinon-holon bound state or resonance due to gauge binding with a Fermi surface respecting the topological Luttinger theorem. In our proposal Fermi arcs are determined by the hole resonance, whereas the metal-insulator crossover is dominated by spinon-spinon (with subleading holon-holon) gauge interactions and this dichotomy is able to explain their coexistence.

Abstract: Due to their rapid evolution and their impact on health care, be-ta-lactamases, protein degrading beta-lactam antibiotics, are used as generic model of protein evolution. Therefore, we investigated the mutation effects in two distant beta-lactamases TEM-1 and CTX-M-15. Interestingly we found a site with a complex pattern of genetic interactions. Mutation G251W in TEM-1 is in-activating the protein’s function just as the reciprocal mutation W251G in CTXM-15. Phylogenetic analysis revealed that mutation G has been entrenched in TEM-1 background: while rarely observed throughout the phylogeny it is es-sential in TEM-1. Using a rescue experiment in TEM-1 G251W mutant, we could identify sites that alleviates the deviation from G to W. While few of these muta-tions could potentially involve local interactions, most of them were found on distant residues in the 3D structure. Many well-known mutations having an impact on protein stability, such as M182T, were recovered. Our results there-fore suggest that entrenchment of an amino acid may rely on diffuse interactions among multiple sites with a major impact on protein stability.

Wnt/β-catenin signaling pathway plays an established role in various diseases and is considered a hallmark of endometrial cancer (EC). Special AT-rich sequence-binding protein 1 and 2 (SATB1 and SATB2) are nuclear matrix-associated proteins involved in chromatin remodeling and regulation of gene expression. SATB1 promotes the progression of numerous types of cancers, whereas SATB2 acts as a tumor suppressor. Despite a recent progress in our knowledge about EC, the exact mechanisms that control their proliferation and metastatic potential still remain unknown. The aim of our study was to investigate the association between Wnt3A, β-catenin, SATB1 and SATB2 protein level and the clinicopathological features of EC patients. 92 EC patients, aged 37-84, were enrolled to our study. The immunoexpression of WNT3A was found in specimens from all EC patients, β-catenin was expressed in 97% of the cases, SATB1 in 87%. The significant association between Wnt3a expression and tumor grade was found; moreover mean IRS for Wnt3a turned out to be significantly lower in high-grade tumors than in low-grade malignancies (p=0.038). In turn, immunoexpression of β-catenin varied significantly across FIGO stages and was associated with the presence of lymph node metastases. Mean IRS for β-catenin in patients with lymph node metastases was significantly lower than in those without (p = 0.028). The Kaplan-Meier analyses demonstrated a stepwise impairment of cancer overall survival with increasing SATB1 expression. In conclusion, both Wnt/β-catenin signaling pathway and SATB1 contribute to progression of EC. Downregulation of β-catenin may predispose to lymphatic spread of EC. In turn, downregulation of Wnt3a seems to be characteristic for high-grade tumors, but probably does not play a role in formation of lymph node metastases. The important role of SATB1 as a predictor of poor survival and could be helpful in establishing a more accurate prognosis in endometrial cancer patients.

We recently reported that in the spinal cord of PPMS or SPMS patients, large areas of periplaque demyelinating lesions extend distance away from plaque borders. Such lesions are characterized by a progliotic TGF-beta 1 signature accompanied by: i) a low-grade inflammatory reaction, ii) an extensive astrocytosis and iii) a process of incomplete demyelination. It was proposed that, while efficiently dampening inflammation in MS spinal cords, TGF-beta 1 could promote astrocytosis, prevent remyelination and possibly trigger alterations of myelin synthesis. In light of these findings, a re-interpretation of two large neuropathological studies performed on MS brains and spinal cords is provided here. While results from these studies clearly showed that active plaques do not display any region-specific distribution, an important point was apparently overlooked and not discussed by the authors: a significantly higher percentage of inactive plaques was found in MS spinal cords as compared to brains and, conversely, the percentage of slowly-expanding (or smoldering) lesions was significantly lower in the spinal cord as compared to the brain. These data indicate that the spinal cord environment may be more favorable to the resolution of inflammation. Downstream of the autoimmune process leading to plaque formation, region-specific mechanisms may thus drive the outcome of active plaques. While inflammation triggers tissue destruction, inflammation may also be needed for effective tissue repair and an inappropriate dampening of inflammatory events may possibly translate into a poor level of remyelination in MS spinal cords. It is proposed here that TGF-beta 1 is involved in such a brain-spinal cord dissociation of active plaques outcome.

In this paper, we introduce a new formulation based on Floquet (Fourier) spectral analysis combined with a spectral modulation technique (and its spatial form) to study strongly coupled sublattices predefined in the infinite and large finite extent of almost periodic antenna arrays (e.g metasurfaces). This analysis is very relevant for dense massive MIMO, intelligent surfaces, 5G, and 6G applications (used for very small areas with a large number of elements such as millimeter and terahertz waves applications). The numerical method that is adopted to model the structure is the method of moments simplified by equivalent circuits MoM GEC. Other numerical methods (as the ASM array scanning method and windowing Fourier method) used this analysis in their kernel that to treat periodic and pseudo-periodic (or quasi-periodic) arrays.

This study investigates the metabolic parallels between stimulated pancreatic beta cells and cancer cells, emphasizing glucose and glutamine metabolism. Addressing the significant public health challenges of Type 2 Diabetes Mellitus (T2DM) and cancer, we aim to deepen understanding of the mechanisms driving insulin secretion and cellular proliferation. Our analysis of anaplerotic cycles and NADPH's role in biosynthesis elucidates their vital functions in both processes. Additionally, we find that both cell types share an antioxidative response mediated by the Nrf2 signaling pathway, glutathione synthesis, and UCP2 upregulation. Notably, UCP2 facilitates the transfer of C4 metabolites, enhancing reductive TCA cycle metabolism. We also uncover that hypoxic responses are transient in beta cells post-stimulation but persistent in cancer cells. By synthesizing these insights, our research suggests novel therapeutic targets for T2DM, highlighting the shared metabolic strategies of stimulated beta cells and cancer cells. This comparative analysis not only illuminates the metabolic complexity of these conditions but also emphasizes the crucial role of metabolic pathways in cell function and survival, offering fresh perspectives for tackling T2DM and cancer challenges.

In this paper, we introduce the (ρ,q)-analogue of the p-adic factorial function. By utilizing some properties of (ρ,q)-numbers, we obtain several new and interesting identities and formulas. We then construct the p-adic (ρ,q)-gamma function by means of the mentioned factorial function. We investigate several properties and relationships belonging to the foregoing gamma function, some of which are given for the case p = 2. We also derive more representations of the p-adic (ρ,q)-gamma function in general case. Moreover, we consider the p-adic (ρ,q)-Euler constant derived from the derivation of p-adic (ρ,q)-gamma function at x = 1. Furthermore, we provide a limit representation of aforementioned Euler constant based on (ρ,q)-numbers. Finally, we consider (ρ,q)-extension of the p-adic beta function via the p-adic (ρ,q)-gamma function and we then investigate various formulas and identities.

Prebiotic dietary fiber supplements are commonly consumed to help meet fiber recommendations and improve gastrointestinal health by stimulating beneficial bacteria and the production of short-chain fatty acids (SCFAs), molecules beneficial to host health. The objective of this research project was to compare potential prebiotic effects and fermentability of five commonly consumed fibers using an in vitro fermentation system measuring changes in fecal microbiota, total gas production and formation of common SCFAs. Fecal donations were collected from three healthy volunteers. Materials analyzed included: pure beta-glucan, Oatwell (commercially available oat-bran containing 22% oat β-glucan), xylooligosaccharides (XOS), WholeFiber (dried chicory root containing inulin, pectin, and hemi/celluloses), and pure inulin. Oatwell had the highest production of propionate at 12 h (4.76 μmol/mL) compared to inulin, WholeFiber and XOS samples (p<0.03). Oatwell’s effect was similar to those of the pure beta-glucan samples, both samples promoted the highest mean propionate production at 24 h. XOS resulted in a significant increase in the genus Bifidobacterium after 24 h of fermentation (0 h: 0.67 OTUs; 24 h: 5.22 OTUs; p = 0.038). Inulin and WholeFiber increased the beneficial genus Collinsella, consistent with findings in clinical studies. All analyzed compounds were fermentable and promoted the formation of beneficial SCFAs.

Schizophrenia comprises various symptom domains, including positive and negative symptoms. Machine learning showed that a) negative symptoms are significantly interrelated with PHEM (psychosis, hostility, excitation, and mannerism) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR); and b) stable phase schizophrenia comprises two distinct classes, namely Major Neuro-Cognitive Psychosis (MNP, largely overlapping with deficit schizophrenia) and Simple NP (SNP). In this study, we recruited 120 MNP patients and 54 healthy subjects and measured the above-mentioned symptom domains. In MNP, there were significant associations between negative and PHEM symptoms, FTD and PMR. A single latent trait, which is essentially unidimensional, underlies these key domains of schizophrenia and MNP and additionally shows excellent internal consistency reliability, convergent validity, and predictive relevance. Confirmatory Tedrad Analysis indicates that this latent vector fits a reflective model. The lack of discriminant validity shows that PHEM and negative symptoms greatly overlap and probably measure the same construct. Soft Independent Modeling of Class Analogy (SIMCA) shows that MNP (diagnosis based on negative symptoms) is better modeled using PHEM symptoms, FTD, and PMR than negative symptoms. In conclusion, in stable phase MNP, a restricted sample of the schizophrenia population, negative and PHEM symptoms, FTD and PMR belong to one underlying latent vector reflecting overall severity of schizophrenia (OSOS). The bi-dimensional concept of “positive” and “negative” symptoms cannot be validated and, therefore, future research in stable phase schizophrenia should consider that the latent phenomenon OSOS as well as its 8 reflective manifestations are the key factors of schizophrenia phenomenology.

Beta-carotene is a fat-soluble antioxidant commonly found in foods such as fruits, vegetables, and palm oil. Despite various liquid chromatography methods are proposed to detect and measure the sera carotenoid level, a long retention time to elute this marker is needed. This study attempted to develop a rapid reverse phase method in eluding beta-carotene in human sera. The researchers managed to elute the antioxidant in 2.2 minutes by applying a combination of a C8 column, mobile phase comprising of acetonitrile mixed with methanol in 70:30 proportion, and an ultra-high performance liquid chromatography system. The outputs had a good calibration curve (R²=0.959) and low coefficient of variation (0.2%), suggesting this protocol is reliable. A column with a lower carbon chain such as C8 allows the beta-carotene molecule to flow through the column faster. Besides, selecting solvents with high elution strength coupled with an ultra-high performance liquid chromatography system which equipped with high pressure can force the beta-carotene through the column in a shorter duration compared to previous reported methods. Therefore, it is recommended to adopt this protocol in epidemiological studies where beta-carotene is screened as a dietary biomarker associated with disease of interest by using human sera in the population level.

During type 1 diabetes mellitus (T1DM) development, beta-cells undergo intense endoplasmic reticulum (ER) stress that could result in apoptosis through the failure of adaptation to the unfolded protein response (UPR). Islet transplantation is considered an attractive alternative among beta-cell replacement therapies for T1DM. To avoid the loss of beta-cells that will jeopardize the transplant´s outcome, several strategies are being studied. We have previously shown that prolactin induces protection against pro-inflammatory cytokines and redox imbalance-induced beta-cell death by increasing heat shock protein B1 (HSPB1) levels. Since the role of HSPB1 in beta cells has not been deeply studied, we investigated the mechanisms involved in unbalanced protein homeostasis caused by intense ER stress and overload of the proteasomal protein degradation pathway. We tested whether HSPB1-mediated cytoprotective effects involved UPR modulation and improvement of protein degradation via the ubiquitin-proteasome system. We demonstrated that increased levels of HSPB1: attenuated levels of pro-apoptotic proteins like CHOP and BIM, increased protein ubiquitination and the speed of proteasomal protein degradation. Our data showed that HSPB1 induced resistance to proteotoxic stress and thus enhanced cell survival via an increase in beta-cell proteolytic capacity. These results could contribute to generate strategies aiming at optimization of beta-cell replacement therapies.

We investigate new graph characteristics namely total (vertex, edge) face irregularity strength of gen- eralized plane grid graphs Gmn under k-labeling Phi of type (Alpha, Beta, Gamma). The minimum integer k for which a vertex-edge labelled graph has distinct face weights is called the total face irregularity strength of the graph and is denoted by tfs(Gmn). In this article, the graphs G = (V;E; F) under consideration are simple, finite, undirected and planar. We will estimate the exact tight lower bounds for the total face irregularity strength of some families of generalized plane grid graphs.

This work communicates a review on Balmer series hydrogen beta line measurements and applications for analysis of white dwarf stars. Laser-induced plasma investigations explore electron density and temperature ranges comparable to white dwarf star signatures such as Sirius B, the companion to the brightest star observable from the earth. Spectral line shape characteristics of the hydrogen beta line include width, peak separation, and central dip-shift, thereby providing three indicators for electron density measurements. The hydrogen alpha line shows two primary line-profile parameters for electron density determination, namely, width and shift. Both Boltzmann plot and line-to-continuum ratios yield temperature. The line-shifts recorded with temporally- and spatially- resolved optical emission spectroscopy of hydrogen plasma in laboratory settings can be larger than gravitational redshifts that occur in absorption spectra from radiating white dwarfs. Published astrophysical spectra display significantly diminished Stark or pressure broadening contributions to red-shifted atomic lines. Gravitational redshifts allow one to assess the ratio of mass and radius of these stars, and subsequently, the mass from cooling models.

There is compelling evidence that the nuclear receptor TRβ, a member of the thyroid hormone receptor (TR) family, is a tumor suppressor in thyroid, breast and other solid tumors. Cell-based and animal studies reveal that the liganded TRβ induces apoptosis, reduces an aggressive phenotype, decreases stem cell populations, and slows tumor growth through modulation of a complex interplay of transcriptional networks. TRβ-driven tumor suppressive transcriptomic signatures include repression of known drivers of proliferation such as PI3K/Akt pathway and activation of novel signaling (JAK1/STAT1) and metabolic reprogramming in both thyroid and breast cancers. The presence of TRβ is also correlated with a positive prognosis and response to therapeutics in BRCA+ and triple-negative breast cancers respectively. Ligand activation of TRβ enhances sensitivity to chemotherapeutics. TRβ co-regulators and bromodomain-containing chromatin remodeling proteins are emergent therapeutic targets. This review considers TRβ as a potential biomolecular diagnostic and therapeutic target.

Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than parent the cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable material for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal and epithelial type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as non-toxic. Based on these results, fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cells protection against oxidative stress.

A powder synthesis of PbMoO₄ from ancient lead (Pb) and deeply purified commercial MoO₃ powders was performed using a wet chemistry technique to achieve the low radioactivity scintillator for neutrinoless double beta decay search in ¹⁰⁰Mo. The synthesized powders were used to grow single crystals of PbMoO₄ by a Czochralski technique in Ar environment. The luminescence and scintillation properties were measured with excitations using UV, X- and γ-rays in temperature range of 10-300 K. Annealing of the grown PMO crystal in air atmosphere enhanced the scintillation light yield by ~3 orders of magnitude compared to that measured before annealing. The scintillation light yield of grown PMO crystal at 10 K is found to be 127% to that of a reference PMO crystal under 662 keV γ-rays excitation from a ¹³⁷Cs source. The background measurement of the grown crystal performed at 50 K shows negligible activity from ²¹⁰Pb compared to that of reference PMO crystal. These preliminary performances show that the PMO crystal grown from ancient Pb and deeply purified MoO₃ powders has the great potential to be used as cryogenic scintillator for the neutrinoless double beta decay search in ¹⁰⁰Mo.

Beta cells couple stimulation by glucose with insulin secretion and impairments in this coupling play a central role in diabetes mellitus. To clarify the effect of cAMP and the role of Epac2A in intracellular calcium signals and intercellular coupling, we performed functional multicellular calcium imaging in beta cells in mouse pancreas tissue slices after stimulation with glucose and forskolin in wild-type and Epac2A knock-out mice. Increased cAMP evoked calcium signals in otherwise sub-stimulatory glucose and beta cells from Epac2A knock-out mice displayed a faster activation. During the plateau phase, beta cells from Epac2A knock-out mice displayed a slightly higher active time in response to glucose compared with wild-type littermates, and increased cAMP increased the active time via a large increase in oscillation frequency and small decrease in oscillation duration in both Epac2A knock-out and wild-type mice. Functional network properties during stimulation with glucose did not differ in Epac2A knock-out mice, but the presence of Epac2A was crucial for the protective effect of increased cAMP in preventing a decline in beta cell functional connectivity with time. Finally, increased cAMP prolonged beta cell activity during deactivation in an Epac2A-independent manner.

Vessel co-option correlates with resistance against anti-angiogenic agents and chemotherapy in colorectal cancer liver metastasis (CRCLM). We previously identified higher intensity of neutrophils in the tumour microenvironment of vessel co-opting CRCLM lesions compared to their angiogenic counterparts. Herein, we demonstrated that over 50% of the neutrophils in vessel co-opting lesions are expressing pro-apoptotic markers including cleaved caspase-3 and poly (ADP-ribose) polymerase-1 (PARP-1). Our previous publications suggested upregulation of transforming growth factor-beta (TGFβ1) in the microenvironment of vessel co-option CRCLM. Therefore, we examined the effect of TGFβ1 on the expression of cleaved caspase-3 and PARP-1 in neutrophils in vitro. Significantly, we noticed the upregulation of pro-apoptotic markers upon exposure to TGFβ1. This finding might pave the way to determine the role of neutrophils in developing vessel co-option in CRCLM in the future.

Abstract: Breast cancer is one of the leading causes of death in the female population due to the re-sistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubil-ity and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxy curcumin magnesium complex with cyclodex-trin (DiMeOC-Mg-BCD, 5) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media (PBS) was improved by a factor of 6x over the free metal complex (DiMeOC-Mg). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the MMP-2 and MMP-9, IL-6, and STAT3 expression levels on MDA MB 231 cell lines. Results of an antitumor assay in an in-ovo model showed up to 30% inhi-bition of tumour growth for breast cancer (MDA-MB-231) when using 5 (0.650 mg/Kg dose), and 17.29 % inhibition with the free homoleptic metal complex (1.5 mg/Kg dose, DiMeOC-Mg). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new DiMeOC-Mg-BCD exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

$\beta$-decay is one of the key factors to understand the $r$-process and evolution of massive stars. The Gamow-Teller (GT) transitions drive the $\beta$-decay process. We employ the proton-neutron quasiparticle random phase approximation (pn-QRPA) model to calculate terrestrial and stellar $\beta$-decay rates for 50 top-ranked nuclei possessing astrophysical significance according to a recent survey \cite{Nab21}. The model parameters of the pn-QRPA model effect the predicated results of $\beta$-decay. The current study investigates the effect of nucleon-nucleon pairing gaps on charge-changing transitions and the associated $\beta$ decay rates. Three different values of pairing gaps, namely TF, 3TF and 5TF, were used in our investigation. It was concluded that both GT strength distributions and half-lives are sensitive to pairing gap values. The 3TF pairing gap scheme, in our chosen nuclear model, resulted in best prediction with around 80$\%$ of the calculated half-lives within a factor 10 of the measured ones. The 3TF pairing scheme also led to calculation of biggest $\beta$-decay rates in stellar matter.

It is well known that the primes and prime powers have a deep relationship with the nontrivial zeros of Riemann’s zeta function. This is a reciprocal relationship. The zeros and the primes are encoded in each other and are reciprocally recoverable. Riemann’s zeta is an extended or continued version of Euler’s zeta function which in turn equates with Euler’s product formula over the primes. This paper shows that the zeros of the converging Dirichlet or Catalan beta function, which requires no continuation to be valid in the critical strip, can be easily determined. The imaginary parts of these zeros have a deep and reciprocal relationship with the odd primes and odd prime powers. This relationship separates the odd primes into those having either 1 or 3 as a remainder after division by 4. The vector pathway of the beta function is such that the real part of its zeros has to be a half.

Background: COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a recurrent endemic disease affecting the whole world. Since November 2021, Omicron and its subvariants are dominating. In order to prevent severe courses of disease, vaccines are needed to boost and maintain antibody levels capable of neutralizing Omicron. Recently we produced and characterized a SARS-CoV-2 vaccine based on a recombinant fusion protein consisting of hepatitis B virus (HBV)-derived PreS and two SARS-CoV-2 wild-type RBDs. Objectives: To develop a PreS-RBD vaccine which induces high levels of Omicron-specific neutralizing antibodies. Methods: We designed, produced, characterized and compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix of W-PreS-W and O-PreS-O) and chimeric (i.e., W-PreS-O) SARS-CoV-2 protein subunit vaccines. Immunogens were characterized in vitro by protein chemical methods, mass-spectrometry, circular dichroism in combination with thermal denaturation and immunological methods. In addition, BALB/c mice were immunized with aluminum hydroxide-adsorbed proteins and aluminum hydroxide alone (i.e., placebo) to study specific antibody and cytokine responses, safety and Omicron neutralization. Results: Defined and pure immunogens could be produced in large amounts as secreted and folded proteins in mammalian cells. Antibodies induced after vaccination with different doses of strain-specific, bivalent and chimeric PreS-RBD fusion proteins reacted with wild-type and Omicron RBD in a dose-dependent manner and resulted in a mixed Th1/Th2 immune response. Interestingly, RBD-specific IgG levels induced by the different vaccines were comparable but the W-PreS-O-induced virus neutralization titers against Omicron (median VNT50: 5000) were 7- and 2-fold higher than the W-PreS-W- and O-PreS-O-specific ones, respectively and 6-fold higher than those of the bivalent vaccine. Conclusion: Among the tested immunogens, the chimeric PreS-RBD subunit vaccine, W-PreS-O, induced the highest neutralizing antibody titers against Omicron. Thus, W-PreS-O seems to be a highly promising COVID-19 vaccine candidate for further preclinical and clinical evaluation.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID Syndrome (PCS). A fraction of the PCS patients develops the full clinical picture of ME/CFS. New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure. Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing constriction of resistance vessels and of precapillary sphincters which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion. The detrimental coincidence of the microcirculatory with the precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in pre-disposed patients because the interaction causes a particular kind of perfusion disturbance - capillary ischemia-reperfusion - which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter in turns worsens the vascular situation by the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.

Cholinergic innervation in pancreas controls both the release of digestive enzymes to support the intestinal digestion and absorption, as well as insulin release to promote nutrient use in the cells of the body. The effects of muscarinic receptor stimulation are described in detail for endocrine beta cells and exocrine acinar cells separately. Here we describe morphological and functional criteria to separate these two cell types in situ in tissue slices and simultaneously measure their response to ACh stimulation on cytosolic Ca2+ oscillations [Ca2+]c in stimulatory glucose conditions. Our results show that both cell types respond to glucose directly in the concentration range compatible with the glucose transporters they express. The physiological ACh concentration increases the frequency of glucose stimulated [Ca2+]c oscillations in both cell types and synchronizes [Ca2+]c oscillations in acinar cells. The pharmacological ACh concentration further increases the oscillation frequency on the level of individual beta cells, inhibits the synchronization between these cells, and abolishes oscillatory activity in acinar cells. We discuss possible mechanisms leading to the observed phenomena.

Study of gross alpha (GA) and gross beta (GB) activity in road and surface deposited sediments were performed in various geographical areas in three Russian cities. To perform radiation measurements, new methods were applied which allow dealing with low mass and low volume dust size (2-100μm) samples obtained after the size fractionation procedure. The 2-10 μm fraction size has the highest gross beta activity concentration (GB)– 1.32Bq/g in Nizhny Novgorod (NN) and Rostov-On-Don (RND) while the 50-100 μm fraction size in Ekaterinburg. This is maybe associated with the subsistence of radionuclides that conveyed through natural processes and anthropogenic applications. The highest gross alpha activity concentration (GA) in fraction sizes was found in Rostov-on-Don city within the 50-100 μm– 0.22Bq/g. The fraction size 50-100 μmhas a higher gross alpha activity concentration than 2-10 and 10-50 μmfraction sizes due to natural partitioning of the main minerals constituting the urban surface deposited sediment (USDS). The geochemical processes that occur during the formation and transportation of USDS are reflected in the observed dependencies.Developed experimental methods of radiation measurements allowed to the extent the methodological base of urban geochemical studies.

In the paper, by convolution theorem for the Laplace transforms and analytic techniques, the author finds necessary and sufficient conditions for complete monotonicity, monotonicity, and inequalities of several functions involving polygamma functions. By these results, the author derives a lower bound of a function related to the sectional curvature of the manifold of the beta distributions. Finally, the author poses several guesses and open problems related to monotonicity, complete monotonicity, and inequalities of several functions involving polygamma functions.

Beta adrenoblockers is a large class of drugs mainly used to manage abnormal heart rhythms. Over the last couples of decades, the anticancer effects of these compounds has been extensively studied. There is much evidence about their activity in non-small cell lung, pancreatic, breast, colorectal, prostate and ovarian cancer. However, the mechanism of beta blockers anticancer activity is still not known, and more detailed studies are needed. The aim of our study was to evaluate the anticancer activity of beta adrenoblockers in non-small cell lung cancer cell lines A549 and H1299. In order to find the relationship with their selectivity to beta adrenoreceptors, in our study we used selective (atenolol, betaxolol, esmolol, metoprolol) and non-selective (pindolol, propranolol and timolol) beta blockers. The effect on cell viability was evaluated by MTT assay and the activity on cell ability to form colonies was tested by clonogenic assay. The type of cell death was evaluated by cell double staining with Hoechst 33342 and Propidium iodide. The most active adrenoblockers against both tested cancer cell lines were propranolol and betaxolol. They completely inhibited lung cancer cell colony formation at 90% of EC50 (half maximal effective concentration) value. Most tested compounds induced cell death through apoptosis and necrosis. In A549 cell lines apoptosis was mainly induced while in H1299 cell line compounds induced both apoptosis and necrosis. There was no correlation established between beta adrenoblocker anticancer activity and their selectivity to beta adrenoreceptors.

One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood–brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ42 containing isomerized Asp7 residue (iso-Aβ42) and Aβ42 containing phosphorylated Ser8 residue crossed the BBB better than unmodified Aβ42, which correlated with different contribution of endocytosis mechanisms to the transport of these isoforms. Using microscale thermophoresis, we observed that RAGE binds to iso-Aβ42 an order of magnitude weaker than to Aβ42. Thus, post-translational modifications of Aβ increase the rate of its transport across the BBB and modify the mechanisms of the transport, which may be important for AD pathology and treatment.

Abstract: Composite sintered bodies comprising silicon dioxide (SiO2) nanoparticles dispersed in β-tricalcium phosphate (β-TCP) were prepared. The addition of nano-sized colloidal SiO2 to the β-TCP produced well-dispersed secondary phase nanoparticles that promoted densification by suppressing grain growth and increasing volume shrinkage of the sintered bodies. The SiO2 was found not to react with the β-TCP at 1120 °C and the substitution of silicon for phosphorous to produce a solid solution did not occur. This lack of a reaction is ascribed to the absence of avail-able calcium ions to compensate for the increase in charge associated with this substitution. The SiO2 nanoparticles were found to be present near the intersections of grain boundaries in the β-TCP. A β-TCP composite sintered body containing 4.0 wt% SiO2 exhibited a bending strength comparable to that of cortical bone and hence could potentially be used as a bone filling material.

Three-dimensional matrices are a new strategy used to tackle type I diabetes; a chronic metabolic disease characterized by the destruction of beta pancreatic cells. Type I collagen is an abundant extracellular matrix (ECM), component that has been used to support cell growth. However, pure collagen possesses some difficulties including low stiffness and strength, and high susceptibility to cell-mediated contraction. Therefore, we developed a collagen hydrogel with a poly(ethylene glycol) diacrylate (PEGDA) interpenetrating network (IPN), functionalized with vascular endothelial growth factor (VEGF) to mimic the pancreatic environment for the sustenance of beta-pancreatic cells. We analyzed the physicochemical characteristic of the hydrogels and found that they were successfully synthesized. The mechanical behavior of the hydrogels improved with the addition of VEGF, and the swelling degree and the degradation were stable over time. In addition, it was found that 5 ng/mL VEGF-functionalized collagen/PEGDA IPN hydrogels sustained and enhanced viability, proliferation, respiratory capacity and functionality of beta pancreatic cells. Hence, this is a potential candidate for future preclinical evaluation, which may be favorable for diabetes treatment.

Antibiotic resistance, particularly beta-lactam resistance, is a major problem worldwide. Imipenemase or IMP-type metallo-beta-lactamase (MBL) has become a more prominent enzyme, especially in Asia, since it was discovered in the 1990s in Japan. There are currently more than 91 variants of IMP-type enzymes. The most commonly identified variant of IMP-type enzymes is IMP-1 variant. IMP-type MBLs have been identified in more than 10 species in Enterobacterales. Pseudomonas aeruginosa is the most frequent carrier of IMP-type enzymes worldwide. In Asia, IMP-type MBLs have been distributed in many countries in the region. This work investigated a variety of currently available IMP-type MBLs in both global level and regional level. Out of 88 variants of IMP-type MBLs reported worldwide, only 32 variants were found to have susceptibility profiles. Most of the IMP-type MBLs were resistant to Carbapenems, especially Imipenem and Meropenem, followed by the 3rd generation cephalosporins, and interestingly, monobactams. Our results comprehensively indicated the distribution of IMP-type MBLs in Asia and raised the awareness of the situation of antimicrobial resistance in the region.

The most widely distributed bla_CTX-M gene on a global scale is bla_CTX-M-15. The dissemination has been associated with clonal spread and different types of mobile genetic elements. This study aimed to review and describe the genetic environments of bla_CTX-M-15 gene detected from Enterobacteriaceae in published literature from Africa. A literature search for relevant articles was done through PubMed, and Google Scholars electronic databases, 43 articles from 17 African countries were included in the review based on the eligibility criteria. Insertion sequences were reported as part of the genetic environment of bla_CTX-M-15 gene in 32 studies, integrons in 13 studies, and plasmids in 23 studies. In this review, five insertion sequences including ISEcp1, IS26, orf447, IS903, and IS3 have been detected associated with the genetic environment of bla_CTX-M-15 in Africa. Seven different genetic patterns were seen in bla_CTX-M-15 genetic environment. Insertion sequence ISEcp1 was commonly located upstream of the end of the bla_CTX-M-15 gene while insertion sequence orf477 was located downstream. In some studies, ISEcp1 was truncated upstream of bla_CTX-M-15 by insertion sequences IS26 and IS3. Class 1 integron (Intl1) was most reported to be associated with bla_CTX-M-15 (13 studies), with Intl1/dfrA17–aadA5 being the most common gene cassette array. IncFIA-FIB-FII multi-replicons and IncHI2 replicon types were the most common plasmid replicon types that horizontally transfer bla_CTX-M-15 gene. Aminoglycoside modifying enzymes, and plasmid-mediated quinolone resistance genes were commonly collocated with bla_CTX-M-15 gene on plasmids. This review revealed the predominant role of ISEcp1, Intl1and IncF plasmid in the mobilization and continental dissemination of the bla_CTX-M-15 gene in Africa.

In this work, we investigated for the first time the complexation of sepiapterin (SP), the natural precursor of the natural essential cofactor tetrahydrobiopterin, that displays mild water-solubility and short biological half-life, with the hydrophobic triacetyl-β-cyclodextrin (TAβCD) to improve its encapsulation within methoxy-poly(ethylene-glycol)-poly(epsilon-caprolactone) (mPEG-PCL) nanoparticles. First, TAβCD-SP complexes were produced by spray-drying of TAβCD/SP binary solutions by utilizing the Nano Spray Dryer B-90 HP. Then, dry powders were characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR) and transmission and scanning electron microscopy (SEM and TEM, respectively) and compared to the complex components and physical mixtures (PMs). Next, SP was encapsulated within methoxy-poly(ethylene-glycol)-poly(epsilon-caprolactone) (mPEG-PCL) nanoparticles by nanoprecipitation of a SP/TAβCD complex/mPEG-PCL solution. In addition to complex nanoencapsulation, we assessed encapsulation of pure SP by nanoprecipitation with an intermediate step, which comprised the co-drying of SP, TAβCD and mPEG-PCL copolymer solution in organic solvent; this step aimed to promote the formation of molecular interactions between SP, TAβCD and the PCL blocks in the copolymer. SP-loaded mPEG-PCL nanoparticles were characterized by dynamic light scattering (DLS) and SEM. Nanoparticles with size of 74-75 nm and small polydispersity index (PDI <0.1) were obtained when SP-TAβCD equimolar spray-dried complex was used for nanoencapsulation, and SEM analysis indicated the absence of free SP crystals. Moreover, the encapsulation efficiency (%EE) and drug loading (DL) were 85% and 2.6%, respectively, as opposed to those achieved with pure SP encapsulation (14% and 0.6%, respectively). Overall, our results confirm that spray-drying of SP/TAβCD solutions at the appropriate molar ratio leads to the hydrophobization of the relatively hydrophilic SP molecule, enabling its encapsulation within mPEG-PCL nanoparticles.

Background: Cancer stem cells (CSCs) exhibit self-renewal activity and give rise to other cell types in tumors. Due to the infinite proliferative potential of CSCs, drugs targeting these cells are necessary to completely inhibit cancer development. beta-lapachone (bL) has been widely used to treat cancer development, but its effect on cancer stem cells remain elusive. Thus, we investigated the effect of bL on mammosphere formation using breast cancer stem cell (BCSC) marker positive cells, MDA-MB-231. Methods: MDA-MB-231 Cells, which is negative for NQO1 expression, was constructed to stably express NQO1(NQO1 stable cells) to see the effect of bL. The effect of bL on cells were evaluated by wound healing and Transwell cell culture chambers, and ALDEFLUOR assay. Results: Here, we show that bL inhibited the proliferative ability of mammosphere derived from BCSC marker-positive cells, MDA-MB-231, in an NQO1-dependent manner. bL treatment efficiently downregulated expression level of BCSC markers CD44, ALDH1A1, and DLGAP5 that recently identified as a stem cell proliferation marker in both cultured cells and mammosphered cells. Moreover, bL efficiently downregulates cell proliferation and migration activities. Conclusions: These results strongly suggest that bL could be a therapeutic agent targeting breast cancer stem cells with proper NQO1 expression.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The interferons (IFNs) were discovered in 1957, and recombinant IFN-β-1b was approved by the US Food and Drug Administration as the first disease-modifying therapy (DMT) for MS in 1993. Since that time, clinical trials and real-world observational studies have demonstrated the effectiveness of IFN therapies. The pivotal intramuscular IFN-β-1a phase 3 trial was the first to demonstrate that a DMT could reduce accumulation of sustained disability in MS. Patient adherence to treatment is higher with intramuscular IFN-β-1a, given once weekly, than with subcutaneous formulations requiring multiple injections per week. Moreover, subcutaneous IFN-β-1a is associated with an increased incidence of injection site reactions and neutralizing antibodies compared with intramuscular administration. In recent years, revisions to MS diagnostic criteria have improved clinicians’ ability to identify patients with MS and have promoted the use of magnetic resonance imaging (MRI) for diagnosis and monitoring. MRI studies show that treatment with IFN-β-1a, relative to placebo, reduces T2 and gadolinium-enhancing lesions and gray matter atrophy. Since the approval of intramuscular IFN-β-1a, several high-efficacy therapies have been approved for MS, though the benefit of these high-efficacy therapies should be balanced against the increased risk of serious adverse events. For some subpopulations of patients, including pregnant women, the safety profile of IFN-β formulations may provide a particular benefit. In addition, the antiviral properties of IFNs may indicate therapeutic opportunities for IFN-β in the treatment of viral infections such as COVID-19.

Patients with transfusion-dependent thalassemia (TDT) show disorders in calcium metabolism. The α-klotho protein is predominantly expressed in tissues that are involved in calcium homeostasis, and lowered levels are associated with bone disease. Aim of the study. To study the associations between low α-klotho status and calcium metabolism in relation to iron status in children with TDT. Methods. α-klotho, calcium, parathyroid hormone (PTH), calcyphosin, vitamin D3, phosphorous, fibroblast growth factor receptor 2 (FGFR2), as well as iron and erythron biomarkers were measured in 60 children with TDT and 30 healthy control children. Results. A meaningful part of TDT patients showed lowered α-klotho levels, and those children also showed low serum total and ionized calcium concentrations. TDT patients showed increased PTH, FGFR2, and calcyphosin and lowered vitamin D3 as compared with healthy children. The α-klotho levels were significantly correlated with total and ionized calcium (positively) and with iron overload biomarkers and the number of blood transfusions (inversely). Partial Least Squares path analysis showed that 40.1% of the variance in serum total calcium could be explained by the regression on α-klotho, vitamin D3 (both positively), and calcyphosin (inversely) and that the effects of the latter are mediated by iron overload and the number of blood transfusions. Conclusion. In TDT, iron overload and its consequences may induce lowered levels of α-klotho which in turn may lead to lower calcium thereby explaining at least in part the effects of TDT on bone metabolism including spontaneous pathological fractures, osteoporosis, osteopenia, and skeletal deformities.

Beta-thalassemia major (β-TM) patients are treated with repeated blood transfusions, which may cause iron overload (IO), which in turn may induce immune aberrations. Patients with β-TM have an increased risk of major depressive disorder (MDD). The aims of the present study are to examine whether repeated blood transfusions, IO and immune-inflammatory responses are associated with MDD in children (6-12 years) with β-TM. The Children’s Depression Inventory (CDI), iron status (serum iron, ferritin, transferrin, TS%) and serum levels of CCL11, IL-1β, IL-10, and TNF-α were measured in β-TM with (n=54) and without (n=57) MDD and in healthy children (n=55). The results show that MDD in β-TM is associated with a greater number of blood transfusions, increased IO and IL-1β levels. Partial Least Squares path analysis shows that 68.8% of the variance in the CDI score is explained by the number of blood transfusions, IO, and increased levels of IL-1β and TNF-α. The latter two cytokines partly mediate the effects of IO on the CDI score, while the effects of blood transfusions on the CDI score are partly mediated by IO and the path from IO to immune activation. IO is also associated with increased IL-10 and lower CCL11 levels but these alterations are not significantly associated with MDD. In conclusion, blood transfusions may be causally related to MDD in β-TM children and their effects are in part mediated by increased IO and the consequent immune-inflammatory response. The results suggest that not only IO and its consequences including inflammation and ferroptosis, but also other factors related to the number of transfusions may cause MDD including psychosocial stressors. Current treatment modalities with folic acid and vitamin C are insufficient to attenuate IO and immune-inflammatory responses and to prevent MDD is children with β-TM undergoing blood transfusions.

Ischemic heart disease is the leading cause of mortality worldwide. There is evidence of the participation of Aβ in thrombosis and clinical manifestations of acute coronary syndromes. In this study, we investigated the correlation of Aβ peptides with myocardial injury and inflammation biomarkers in acute coronary syndrome. This is a single-center, cross-sectional, observational, and correlation study that included 65 patients within the first 12 hours after symptom onset (chest pain, shoulder pain, or chest discomfort) with ST-elevation and non-ST elevation myocardial infarction who were admitted in the Coronary Care Unit, biochemical parameters of Aβ peptides levels were evaluated. Our results show that NSTEMI patients had a higher prevalence of hypertension, diabetes, smoking, and prior myocardial infarction when compared to STEMI patients. We observed a higher level of Aβ-42 in NSTEMI, but no difference in Aβ-40 levels. We also found a correlation between age and NT-proBNP with both Aβ peptides (Aβ-40, Aβ-42) in both groups. In this analysis, NSTEMI patients had higher prevalence of cardiovascular risk factors. Considering the toxic properties of Aβ-42 in coronary endothelial cells and cardiomyocytes, this peptide may be useful in risk stratification scores in patients with NSTEMI.

Abstract: Beetroot (Beta vulgaris L) has been known for being a rich source of phytochemicals, minerals and vitamins. This study presents a model system for how the combination of extrac-tion/chromatography/mass spectrometry and NMR offers an efficient way to profile metabolites in the extracts of a natural product, beetroot . Such combination may lead to the identification of more nutritional or medicinal compounds in natural products, and it is essential for our ongoing investigation to study the selective adsorption/desorption of these metabolites on nanoparticles. The aqueous and organic extracts underwent analyses using UV-vis spectroscopy; GC-MS; LC-MS; 1H, 13C, TOCSY, HSQC, and selective TOCSY NMR experiments. Polar Extract: The two forms of betalain pigment were identified by UV-vis and LC MS. Fourteen amino acids, sucrose, and other compounds among which is riboflavin, were identified by LC-MS. 2D TOCSY showed the spin coupling correlations corresponding to some of these compounds. The HSQC spectrum showed 1H/13C spin correlation in sucrose confirming the high abundance of sucrose in beetroot. Organic Extract: GC-MS data enabled the identification of several compounds including six fatty acid methyl esters (FAME) with higher than, on average, 90% similarity score. Selective TOCSY NMR data showed the spin coupling pattern corresponding to oleic, linoleic, and linolenic fatty acids. 31P NMR spectra indicate that phospholipids exist in both the organic and aqueous phases. Keywords: Beetroot (Beta vulgaris L); Total Correlation Spectroscopy (TOCSY); Gas Chromatog-raphy-Mass Spectrometry (GC-MS); selective TOCSY, Homonuclear single quantum correlation (HSQC); fatty acid methyl esters (FAME).

Background: Multidrug-resistant bacteria present resistance mechanisms against β-lactam antibiotics, such as Extended-Spectrum Beta-lactamases (ESBL) and Metallo-β-lactamases enzymes (MBLs) operon encoded in Gram-negative species. Likewise, Gram-positive bacteria have evolved other mechanisms through mec genes, which encode modified penicillin-binding proteins (PBP2). This study aimed to determine the presence and spread of β-lactam antibiotic resistance genes and the microbiome circulating in Quito’s Public Transport (QTP). Methods: A total of 29 station turnstiles were swabbed to extract the surface environmental DNA. PCRs were performed to detect the presence of 13 antibiotic resistance genes and to identify 16S rDNA barcoding, followed by clone analysis, Sanger sequencing and BLAST search. Results: ESBL genes blaTEM-1 and blaCTX-M-1 and MBL genes blaOXA-181 and mecA were detected along QPT stations. Two subvariants were found for blaTEM-1, blaCTX-M-1, and blaOXA-181. Almost half of the circulating bacteria found at QPT stations were common human microbiota species including those classified by the WHO as pathogens of critical and high-priority surveillance. Conclusions: β-lactam antibiotic resistance genes are widely spread throughout QPT. This is the first report of blaOXA-181 in environmental samples in Ecuador. Moreover, we detected a new putative variant of this gene. Some commensal coagulase-negative bacteria may have a role as mecA resistance reservoirs

Background/Aim: There is continuing interest in engineering esthetic labial archwires. The aim of this study was to coat nickel-titanium (NiTi) and beta-titanium (β-Ti), also known as titanium molybdenum (TMA), archwires by plasma electrolytic oxidation (PEO) and to analyze the characteristics of the PEO-surfaces. Materials and Methods: PEO-coatings were generated on 0.014-inch NiTi and 0.19x0.25-inch β-Ti archwires. The surfaces were analyzed by scanning electron microscopy and stereomicroscopy. Cytocombability testing was performed with ceramized and untreated samples according to EN ISO 10993-5 in XTT-, BrdU- and LDH-assays. The direct cell impact was analyzed using LIVE-/DEAD-staining. In addition, the archwires were inserted in an orthodontic model and photographs were taken before and after insertion. Results: The PEO coatings were 15 to 20 µm thick and esthetically pleasing. The cytocompatibility analysis revealed good cytocompatibility results for both ceramized NiTi and β-Ti archwires. In the direct cell tests, the ceramized samples showed improved compatibility as compared to those of uncoated samples. However, bending of the archwires resulted in loss of the PEO-surfaces. Nevertheless, it was possible to insert the β-Ti PEO-coated archwire in an orthodontic model without loss of the PEO-ceramic. Conclusion: PEO is a promising technique for the generation of esthetic orthodontic archwires. Since the PEO-coating does not resist bending, its clinical use seems to be limited so far to orthodontic techniques using straight or pre-bended archwires.

Pyracantha angustifolia has been used in traditional medicine to treat a range of diseases of the stomach and improve digestion, blood circulation, diarrhea, dysentery, and hemostasis. This study evaluated bioactivity-guided fractionation as a means to identify therapeutic phytochemicals from P. angustifolia that can attenuate melanogenesis and oxidation. Seven compounds with inhibitory effects on melanin production and tyrosinase (TYR) activity, as well as ABTS and DPPH radical scavenging activities, and have not been reported as whitening materials, were isolated from the n-butanol fraction from P. angustifolia leaves (PAL). Among the seven compounds, p-hydroxybenzoic acid beta-d-glucosylester (HG), and cimidahurinine (CD) had strong inhibitory effects of melanin production, TYR activity, and ABTS and DPPH radical scavenging activities. Western blot analysis showed that HG and CD suppressed tyrosinase-related protein (TYRP)-1 and TYRP-2 expression. These results suggest that P. angustifolia containing active compounds, such as HG and CH, is a potent therapeutic candidate for the development of hypopigmenting agents.