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

Audio recording in classrooms is a common practice in educational research, with applications ranging from detecting classroom activities to analysing student behaviour. Previous research has employed neural networks for classroom activity detection and speaker role identification. However, these recordings are often affected by background noise that can hinder further analysis, and the literature has only sought to identify noise with general filters and not specifically designed for classrooms. Although the use of high-end microphones and environmental monitoring can mitigate this problem, these solutions can be costly and potentially disruptive to the natural classroom environment. In this context, we propose the development of a neural network model that can specifically detect and filter out background noise in classroom recordings. This model would allow the use of lower quality recordings without compromising analysis capability, thus facilitating data collection in natural educational environments and reducing the costs associated with high-end recording equipment.

(1) Background: The severity of malaria is associated with low bioavailability of antioxidants and high concentration of free radicals that induce oxidative damage in cerebral and pulmonary microcirculation. This can be prevented by the action of consumable antioxidants present in foods. Therefore, we investigated the protective role of lycopene (LYC) on the oxidative changes induced by Plasmodium berghei (Pb); (2) Methods: Mice were infected by intraperitoneal injection of 106 parasitized red blood cells and treated via gavage with LYC (3.11 mg/kg bw/day) or NAC (62 mg/kg bw/day). They were then evaluated for 1, 4, 8 or 12 days after infection. Levels of thiobarbituric acid reactive substances (TBARS), antioxidant capacity by inhibition of ABTS radicals (AC-ABTS) and DPPH (AC-DPPH), uric acid (UA), and nitric oxide (NO) were measured in brain and lung tissues; (3) Results: The infection caused oxidative stress confirmed by increased levels of TBARS, AC-ABTS, AC-DPPH, UA, and NO in the tissues leading to the death of the animals. LYC prevented the increase in TBARS, AU, and NO levels compared to Pb (p< 0.0001) and NAC+Pb groups (p<0.0001), reaching values similar to those of Sham animals; (4) Conclusions: These results are striking evidence of the beneficial effect of lycopene supplementation on oxidative stress in experimental malaria in vivo and emphasize the importance of antioxidant supplementation in the treatment of the disease.

We assume that the current mathematical knowledge K is a finite set of statements from both formal and constructive mathematics, which is time-dependent and publicly available. Any theorem of any mathematician from past or present belongs to K. The set K exists only theoretically. Ignoring K and its subsets, sets exist formally in ZFC theory although their properties can be time-dependent (when they depend on K) or informal. In every branch of mathematics, the set of all knowable truths is the set of all theorems. This set exists independently of K. Algorithms always terminate. We explain the distinction between algorithms whose existence is provable in ZFC and constructively defined algorithms which are currently known. By using this distinction, we obtain non-trivial statements on decidable sets X⊆N that belong to constructive and informal mathematics and refer to the current mathematical knowledge on X. This and the next sentence justify the article title. For any empirical science, we can identify the current knowledge with that science because truths from the empirical sciences are not necessary truths but working models of truth from a particular context. The feature of mathematics from the article title is not quite new. Church's thesis, which is known from the beginning of computability theory, is based on the observation that the currently known computable functions are recursive, where the notion of a computable function is informal. It proves that the predicate of the current mathematical knowledge slightly increases the intuitive mathematics. For a set X⊆N whose infiniteness is false or unproven, we define which elements of X are classified as known. No known set X⊆N satisfies Conditions (1)-(4) and is widely known in number theory or naturally defined, where this term has only informal meaning. (1) A known algorithm with no input returns an integer n satisfying card(X)<ω ⇒ X⊆(-∞,n]. (2) A known algorithm for every k∈N decides whether or not k∈X. (3) No known algorithm with no input returns the logical value of the statement card(X)=ω. (4) There are many elements of X and it is conjectured, though so far unproven, that X is infinite. (5) X is naturally defined. The infiniteness of X is false or unproven. X has the simplest definition among known sets Y⊆N with the same set of known elements. We prove that the set X={n∈N: the interval [-1,n] contains more than 29.5+(11!/(3n+1))∙sin(n) primes of the form k!+1} satisfies Conditions (1)-(5) except the requirement that X is naturally defined. 501893∈X. Condition (1) holds with n=501893. card(X∩[0,501893])=159827. X∩[501894,∞)={n∈N: the interval [-1,n] contains at least 30 primes of the form k!+1}. If we add to X some set W satisfying 14≤card(W)≤23, then the following statements hold: X does not satisfy Condition (1), 159827+14≤card(X), the above lower bound is currently the best known, card(X)<ω ⇒ card(X)≤159827+23, the above upper bound is currently the best known, X satisfies Conditions (2)-(5) except the requirement that X is naturally defined. Analogical statements hold, if we add to X the set ⋃_{x∈N, x divides 99!} {k∈N: k-501894 is the x-th element of P(n^2+1)}, where P(n^2+1) denote the set of primes of the form n^2+1. For a non-negative integer n, let θ(n) denote the largest integer divisor of 10^{10^{10}} smaller than n. Let κ:N→N be defined by setting κ(n) to be the exponent of 2 in the prime factorization of n+1. The set X={n∈N: (θ(n)+κ(n))^2+1 is prime} satisfies Conditions (1)-(5) except the requirement that X is naturally defined. Condition (1) holds with n=0^{10^{10}}. We present a table that shows satisfiable conjunctions of the form #(Condition1)∧ (Condition 2)∧#(Condition 3)∧(Condition 4)∧#(Condition 5), where # denotes the negation ¬ or the absence of any symbol. No set X⊆N will satisfy Conditions (1)-(4) forever, if for every algorithm with no input, at some future day, a computer will be able to execute this algorithm in 1 second or less. The physical limits of computation disprove this assumption.

The plant Allium hookeri, belonging to the Allium genus, has a history of being used both as a common food ingredient and in herbal medicine. It has recently been reported to have anti-oxidant and anti-inflammatory effects. A. hookeri has been also shown to exhibit neuroprotective and anti-neuroinflammatory activities, but the active compounds responsible for these effects have not been identified in previous studies. This study aimed to perform a metabolite profiling using an HRESI-qTOF MS/MS-based molecular networking approach and identify the active compounds from A. hookeri that target senescent cell-associated secretory phenotype (SASP) inhibitory effects, which contribute to neuroprotective activities. As a result, ten compounds, including one new flavonoid (2) and nine known compounds (1 and 3–10), were identified, and their biological activity was tested. The most potent compound was N-trans-feruloyltyramine (7), which inhibited SASP markers and contributed to the senomorphic activities of A. hookeri. These findings suggest that the phenolamides from A. hookeri could be a promising source of bioactive compounds for preventing senescence-associated diseases.

This article explores the relationship between convex functions defined on integers ($\mathbb{Z}$) and their extension to real numbers ($\mathbb{R}$). We introduce key definitions and investigate the hypothesis that there exists a unique convex curve within this family of functions, leading to a proof by contradiction. Our findings highlight the preservation of convexity as functions transition from integers to real numbers.

Given a set of distinct non-negative integers X^n and a target certificate S in parametrized form: ∃X^k⊆X^n,∑_(x_i∈X^k)▒x_i =S (k=|X^k |,n=|X^n |). We present a polynomial solution of the subset sum problem with time complexity T≤O(kn)≤O(n^2) and space complexity S≤O(((n-1)n)/2)≤O(n^2 ), so that P = NP.

The effect of neutron irradiation of Si-Ge/Si film structures obtained by gas-phase epitaxy on the processes of charge carrier generation and the magnitude of the dark short-circuit current and open-circuit voltage caused by it is studied, it is shown that their magnitude practically does not change with time. The results obtained indicate that all types of structural defects, both associated with dopant impurities and radiation exposure, contribute to the generation of charge carriers in heated silicon structures with the participation of deep energy levels, which indicates the applicability of neutron processing of silicon materials to create thermal energy converters, operating at high temperatures.

A two-step, one-pot synthesis of 3-substituted 1H-dibenzo[e,g]indazoles in good to high yields via a LiOtBu-promoted intramolecular cyclization of 2’-alkynyl-biaryl-2-aldehyde N-tosylhydrazones, formed in situ by the reactions of 2’-alkynyl-biaryl-2-aldehydes with p-methylbenzenesulfonohydrazide was developed. Two kinds of hydrogen bonds forming in several products were observed in DMSO-d6 solution in 1H NMR spectroscopic data, which were assigned to the formation of solvated products and dimers of products, supported by the studies of density functional theory (DFT).

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.

Flexible capacity applications demands to large energy storage density and high breakdown electric field strength of flexible films. Here, P(VDF-HFP) with ultra-thin Al2O3 nanosheets composite films were designed and fabricated through an electrospinning process followed by hot-pressing in sandwich structured. The results show that the insulating ultra-thin Al2O3 nanosheets and the sandwich structure can enhance the composites' breakdown field (by 24.8%) and energy density (by 30.6%) remarkedly to P(VDF-HFP) polymer matrix. An energy density of 23.5 J/cm3 at the ultrahigh breakdown field of 740kV/mm can be therefore realized. Insulating test and phase-field simulation results reveal that ultra-thin nanosheets insulating buffer layers can reduce the leakage current in composites, thus it effects the electric field spatial distribution to enhance breakdown strength. Our research provides a feasible method to increase the breakdown strength of ferroelectric polymers, which is comparable to those of non-ferroelectric polymers.

We suggest a new solution to the strong CP problem. The solution is based on the proper use of the boundary conditions for the QCD generating functional integral. It obeys the principle of renormalizability of Quantum Field Theory and does not involve new particles like axions.

(1) Background: The typical transporter protein, P-glycoprotein (P-gp), has been proven to be associated with multidrug resistance (MDR). Pyxinol and 24S-Pyxinol amino acid ester derivatives had been demonstrated to be promising P-gp inhibitors for reversal of tumor MDR in KBV cells, however, their roles in MDR reversal in other tumor-resistant cells are still unclear. (2) Methods: In the present study, we synthesized 40 amino acid ester derivatives of Pyxinol and 24S-Pyxinol. The MDR reversal effects of these derivatives were evaluated in A549/Tax, MCF-7/ADR, and HCT-8/VCR cells using the CCK-8 assay. Subsequently, western blot assay, intracellular Rhodamine123 (Rh123) accumulation assay and P-gp ATPase activity assay were utilized to investigate the effects of active compound on P-gp. Molecular docking was used to predict the possible binding patterns of active compound to P-gp. Moreover, based on UPLC-Q/TOF-MS cellular metabolomics technology to identify endogenous differential metabolites and metabolic pathways associated with tumor MDR effects of the active compound. (3) Results: The results of the CCK-8 assay showed that compounds 8, 14, 16, 17, 18, 23, 25, 34, 36, 37 exhibited strong MDR reversal effect in A549/Tax, MCF-7/ADR and HCT-8/VCR cells, which were screened by reversal fold (RF) greater than 5. Among them, 10 μM of derivative 37 (new compound) showed the outstanding activity (RF: 15.31) in reversing MDR in A549/Tax cells. Compound 37 could act as a substrate for P-gp and inhibit the efflux function of P-gp by competitively binding to the binding site of antitumor drugs. Meanwhile, the molecular docking results confirmed that compound 37 was identified to under-go high-affinity binding to the drug binding site of P-gp. In addition, 14 endogenous differential metabolites and 6 metabolic pathways involved closely associated with the reversal of tumor MDR effects of compound 37 were identified. (4) Conclusions: Overall, a new candidate compound 37 (24S-3-L-threonyl-Pyxinol) could be provided for reversing tumor MDR by this study.

A mixture of nonlabeled (14N2H4) and 15N labeled hydrazine (15N2H4) in an aqueous solution is oxidized to 15N2, 14N2, and 14N15N molecules, indicating the intermediate existence of the 14NH2-14NH-15NH-15NH2 with subsequent hydrogen transfers and splitting of side N-N bonds. Structures, thermodynamics, and electron characteristics of various N4H6 molecules in aqueous solutions are investigated using theoretical treatment at the CCSD/cc-pVTZ level of theory to explain the crucial part of the hydrazine oxidation reaction. Most N4H6 structures in aqueous solutions are decomposed during geometry optimization. Splitting the bond between central nitrogen atoms is the most frequent, but the breakaway of the side nitrogen is energetically the most preferred. The N-N fissions are enabled by suitable hydrogen rearrangements. Gibbs free energy data indicate the dominant abundance of NH3... N2... NH3 species. The side N atoms have very high negative charges, which should support hydrogen transfers in aqueous solutions. The only stable cyclo-(NH)4…H2 structure has a too high Gibbs energy and breaks the H2 molecule. The remaining initial cyclic structures are split into hydrazine and HN≡NH or H2N≡N species, and their relative abundance in aqueous solutions is vanishing.

The rationalization and modeling of an electric discharge in a fluid require the knowledge of electron swarm parameters. In this work, transport coefficients of alcohols, including methanol, ethanol, propanol, and butanol are reported. The electron energy distribution function, mean energy, reduced mobility, and diffusion coefficient, are calculated using the two-term expansion of the electron Boltzmann equation in the frame of BOLSIG+ and the Monte Carlo collision code METHES. For such, experimental and theoretical values of the electron-alcohol collision cross-section, covering a range of electron impact energy from 1 eV to 1000 eV, are employed. A temperature of 300K, reduced fields E/N between $1-10^4$ Td (1Td = $10^{-21}~\rm Vm^2$), and Plasma density of $10^{19}~\rm m^{-3}$ were used in simulations. The calculated coefficients are compared with data available from previous studies.

A series of novel substituted isoxazolidine derivatives was synthesized through 1,3-dipolar cycloaddition reactions of α-aryl-N-methyl nitrones with various ethylene moieties, resulting in the formation of isoxazolidine derivatives. The structures of the synthesized compounds were characterized using spectroscopic methods. The [3+2] cycloaddition (32CA) reactions of α-aryl-N-methyl nitrones with diverse ethylene substituents were computed employing Density Functional Theory (DFT) at the B3LYP/6–31G(d) level, upgrading bond parameters. An investigation of the electron localization function (ELF) unveiled the zwitterionic nature of α-aryl-N-methyl nitrones, devoid of pseudoradical or carbenoid centers. Utilization of CDFT indices enabled the prediction of global electronic flux from the strongly nucleophilic α-aryl-N-methyl nitrones to the varied electrophilic ethylene functionalities. Molecular docking and molecular dynamics simulations were conducted on the isoxazolidine derivatives against the EGFR receptor (PDB: 4ZAU). In silico assessment of the synthesized isoxazolidines involved molecular docking, wherein the compound with the highest docking score was subjected to molecular dynamics simulations. Compound 11a, out of the thirty isoxazolidine derivatives, displayed the most substantial binding energy, yielding a g score of -6.57 kcal/mol. These observations highlighted the functional role of amide NH2 and NO2 in the binding process with the target protein, influencing its activity. Furthermore, prediction of ADME drug-likeness properties was performed to identify a suitable candidate.

In this paper, we concentrate on the study of the properties of residual Tsallis entropy for order statistics. Order statistics have an important role in reliability structural engineering for example for modelling lifetimes of series and parallel systems. The residual Tsallis entropy of ith order statistic from a continuous distribution function and its deviation from the residual Tsallis entropy of ith order statistics from a uniform distribution is investigated. In a mathematical framework, a method to express the residual Tsallis entropy of the ith order statistic from a continuous distribution in terms of the residual Tsallis entropy of the ith order statistic from a uniform distribution is provided. This approach may provide insight into the behavior and properties of the residual Tsallis entropy for order statistics. Further, we study the monotonicity properties of the residual Tsallis entropy of order statistics under dierent conditions. By studying these properties, deeper understanding of the relationship between the position of order statistics and the resulting residual Tsallis entropy is gained.

LiFePO4 (LFP) has undergone extensive research and is a promising cathode material for Li-ion batteries. The high interest is due to its low raw material cost, good electrochemical stability, and high-capacity retention. However, poor electronic conductivity and a low Li+ diffusion rate decrease its electrochemical reactivity, especially at fast charge/discharge rates. In this work, the volumetric energy density of lithium-ion batteries is successfully increased by using different amounts of conductive carbon (Super P) in the active material content. The particle size and morphology of the electrode material samples are studied using field emission scanning electron microscopy and dynamic light scattering. Two-point-probe DC measurements and adhesive force tests are used to determine the conductivity and evaluate adhesion for the positive electrode. Cyclic voltammetry, electrochemical impedance spectroscopy (EIS), and charge/discharge tests are used to analyze the electrochemical properties of the battery. The samples containing 88% LFP, 5.5% Super P and 6.5% PVDF perform best, with discharge capacities reaching 169.8 mAhg-1 at 0.1C, and they can also manage charging/discharging of 5C. EIS indicates that this combination produces the lowest charge-transfer impedance (67 Ω) and the highest Li+ ion diffusion coefficient (5.76 x 10-14 cm2s-1).

The development of mineral resources in China has gradually entered the stage of deep mining. Rock burst, collapse and other ground pressure disasters caused by deep high stress have become major hidden dangers restricting mine safety production. Microseismic monitoring technology is an important means of ground pressure risk prediction. In this paper, the wavelet coefficient threshold denoising method in time-frequency domain, STA/LTA method, AIC method, Skew and Kurtosis method are studied, and the automatic P-phase onset time picking model based on noise reduction and multiple detection indexes is established. Through the effect analysis of microseismic signals collected by microseismic monitoring system of coral Tungsten Mine in Guangxi, automatic P-phase onset time picking is realized. the reliability of the P-phase onset time picking method proposed in this paper based on noise reduction and multiple detection indexes is verified. The picking accuracy can still be guaranteed under the severe signal interference of background noise, power frequency interference and manual activity underground mine, Which is of great significance to the data processing and analysis of microseismic monitoring.

Weak contact metric structures on a smooth manifold, introduced by V. Rovenski and R. Wolak in 2022, have provided new insight into the theory of classical structures. In this paper, we define new structures of this kind (called weak nearly Sasakian and weak nearly cosymplectic and nearly K\"{a}hlerian structures) and study their geometry. We introduce weak nearly K\"{a}hlerian manifolds (generalizing nearly K\"{a}hlerian manifolds) and characterize weak nearly Sasakian and weak nearly cosymplectic hypersurfaces in such Riemannian manifolds.

Pancreatic neuroendocrine tumor (P-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional P-NETs, typically when liver metastases occur. NETs diagnosis is frequently late, along with symptoms related to hormone hypersecretion. We described the case of a patient with a low-grade non-functional P-NET, but with a typical clinical presentation of a carcinoid syndrome; moreover, we reviewed the literature regarding this topic. An 81-year-old male was admitted to our Department of Internal Medicine at Cannizzaro Hospital (Catania, Italy) because of the onset of abdominal pain with nausea, loose stools and episodic flushing. Firstly, an abdominal contrast-enhanced CT scan showed a small pancreatic hypervascular mass; then a gallium-68 DOTATOC integrated PET/CT revealed an elevated expression of SSTR receptors. Serum Chromogranin A and urinary 5-HIAA measurements resulted negative. Given the small size of the lesion (8 mm), we preferred to perform an endoscopic ultrasonography (EUS) with fine-needle biopsy (EUS-FNB), allowing the diagnosis of low-grade (G1) non-functional P-NET (NF-P-NET). Surgery was waived, while a follow-up strategy was chosen. Early recognition of P-NETs, although rare, is necessary to improve patient’s survival. EUS-FNB should be the protocol of choice for an early characterization of these tumors.

Cancer researchers are fascinated by the chemistry of diverse natural products which show exciting potential as anticancer agents. In this study, we aimed to investigate the anticancer properties of watermelon rind extract (WRE) by examining its effects on cell proliferation, apoptosis, senescence, and global gene expression in human renal cell adenocarcinoma cells (HRAC-769-P) in vitro. Our metabolome data analysis of WRE exhibited untargeted phyto-constituents and targeted citrulline (22.29 µg/mg). HRAC-769-P cells were cultured in RPMI-1640 media and treated with 22.4, 44.8, 67.2, 88.6, 112, 134.4, and 156.8 mg mL-1 for 24, 48, and 72 hrs. At 24 hrs after treatment, (88.6 mg ml-1 of WRE) cell proliferation significantly reduced, more than 34% compared to the control. Cell viability decreased 48 and 72 hours after treatment to 45% and 37%, respectively. We also examined poly caspase, SA-beta-galactosidase (SA-beta-gal), and wound healing activities using WRE. All treatments induced an early poly caspase response and a significant reduction in cell migration. Further, we analyzed the transcript profile of the cells grown at 44.8 mg ml-1 of WRE after 6 hours using RNA sequencing (RNAseq) analysis. We identified 186 differentially expressed genes (DEGs), including 149 upregulated genes and 37 downregulated genes, in cells treated with WRE compared to the control. The differentially expressed genes were associated with NF-Kappa B signaling and TNF pathways. Crucial apoptosis-related genes such as BMF, NPTX1, NFKBIA, NFKBIE, and NFKBID might induce intrinsic and extrinsic apoptosis. Another possible mechanism is a high quantity of citrulline may lead to induction of apoptosis by the production of increased nitric oxide. Hence, our study suggests the potential anticancer properties of WRE and provides insights into its effects on cellular processes and gene expression in HRAC-769-P cells.

Abstract: (1) Background: Surgery is the best curative option for Gastric Cancer (GC). However, morbimortality associated with surgery still a significant problem. Thus, it is essential to determine the preoperative surgical risk, to optimize outcomes in higher risk patients. (2) Methods: Patients who underwent curative gastrectomy between January 2010 and December 2013 were included, obtaining a sample of 131 patients, and the acuity of the scales understudy was evaluated. The predictive power of the scales was evaluated through calibration and discrimination. (3) Results and Conclusions: Regarding mortality, the scales demonstrated good calibration, with POSSUM and P-POSSUM obtaining the best O:E ratio. The scales presented good discrimination, with POSSUM showing the best result. Considering morbidity, the scales showed good calibration and discrimination. POSSUM and P-POSSUM seem to have potential in predicting morbidity and mortality when applied to the studied population, but there is a need for further studies in this area.

In this study, we investigate the existence of positive solutions within a system of Riemann-Liouville fractional differential equations that incorporate the (r1,r2,r3)-Laplacian operator while being subject to three-point boundary conditions. These equations incorporate various fractional derivatives and are influenced by parameters represented as (ψ1,ψ2,ψ3). Our approach involves employing techniques such as cone expansion and compression of the functional type, in conjunction with the Leggett-Williams fixed point theorem, to establish the existence of positive solutions. To emphasize the practical significance of our findings in the realm of fractional differential equations, we provide two illustrative examples.

Clopidogrel is one of the most prescribed antiplatelet drugs for cardiovascular diseases prevention. Clopidogrel is a prodrug metabolised by CYP2C19 in active metabolites with anti-aggregant effect. Pharmacogenetic variants such as CYP2C19*2 variant can alter the anti-aggregant effect of clopidogrel leading to a higher risk of cardiovascular disease relapse. The aim of this study was to evaluate the prescription characteristics of CYP2C19 pharmacogenetics in patients on clopidogrel treatment, based on a specific query in a clinical data warehouse. We evaluated the demographics of patients, prescribers, medical indications, CYP2C19 pharmacogenetic tests and therapeutic changes. Neurologists were the main prescribers of CYP2C19 pharmacogenetic tests associated with clopidogrel treatment in a context of suspicion of stroke relapse. Pharmacogenetic tests were mainly prescribed a posteriori to clopidogrel prescription. Clopidogrel pharmacogenetic resistance was associated with the prescription of lysine acetylsalicylate in substitution of clopidogrel. Clear clinical practice guidelines are needed to position CYP2C19 pharmacogenetic testing for patients on clopidogrel treatment.

A hydrophilic silica-based stationary phase with surface bound N-acetylglucosamine (GlcNAc-silica) was prepared in house and characterized physically via Fourier transform infrared (FTIR) and thermogravimetric analysis (TGA) and chromatographically over a wide range of mobile phase compositions. While both FTIR and TGA confirmed the attachment of the GlcNAc ligands to the silica surface, the chromatographic evaluation of the GlcNAc-silica with polar and slightly polar standard solutes (e.g., sugars, nucleic acid fragments, phenolic and benzoic acid derivatives) yielded the typical hydrophilic interaction liquid chromatography (HILIC) behaviors in the sense that retention increased with increased solute’s polarity and the organic content (i.e., acetonitrile) of the hydro-organic mobile phase (i.e., ACN-rich mobile phase). Sugars derivatized with 1-naphthylamine (1-NA) and 2-aminoanthrcene (2-AA) such as xylose, glucose and short chains maltooligosaccharides constituted the most polar species for HILIC retention evaluation, and in addition the maltooligosaccharides offered a polar homologous series for gauging the hydrophilicity of the GlcNAc-silica in analogy with alkylbenzene homologous series and other nonpolar homologous for evaluating the hydrophobicity of non-polar stationary phases. On the other hand, the benzoic acid and phenolic acid derivatives were the probe solutes for evaluating the HILIC retention dependence of ionizable solutes on the pH of the mobile phase. Similarly, the nucleobase and nucleoside weak basic solutes as well as some typical cyclic nucleotide acidic solutes allowed the examination of the dependence of solute retention on the pH of the mobile as well as the polarity of the species.

Neuroinflammation is considered to be a significant component in a range of neuropathologies. Unfortunately, whilst its role is well recognized, the options for therapeutic intervention are limited. As such, there is a need to identify novel targets in order to increase treatment options. Given its role as both a neurotransmitter and an immune modulator, substance P and its NK1 receptor have been widely studied as a potential therapeutic target. There is evidence that NK1 receptor antagonists may exert beneficial effects in a range of conditions, including traumatic brain injury and stroke. Blocking the NK1 receptor has been shown to reduce blood-brain barrier dysfunction, reduce cerebral oedema, and reduce the levels of pro-inflammatory cytokines. These actions are associated with improved survival and functional outcomes. The NK1 receptor has also been shown to be involved in the inflammatory reaction to CNS infection, and hence antagonist may have some benefit in reducing infection-driven inflammation. However, the NK1 receptor may also play a role in the host immune response to infection, and so here, the potential beneficial and detrimental effects need to be carefully balanced. As such, the purpose of this review is to provide a summary of the involvement of substance P in acute inflammation, particularly in the context of traumatic brain injury and stroke.

Balanced nitrogen (N) and phosphorus (P) rates coupling with rational fertilization methodology could promote crop N accumulation, N use efficiency and yield production, particularly in semi-arid and arid regions. To test these characteristics, a two-year (2018 and 2019) pot experiment was therefore performed by growing summer maize in a rain-proof glass greenhouse, under 9 combined N (112, 150 and 187 kg ha-1, urea) and P (45, 60, 75 kg ha-1, calcium superphosphate) rates and three contrasting fertilizer placements. The fertilizers were placed by broadcast on soil surface (Broadcast), side band on 4 cm strip soil surface within 7 cm from sowing line (Side band) and deep band on 4 cm strip below 7 cm soil depth within 7 cm from sowing line (Deep band). Results from three maize growth stages (eight-leaf, 45 days after sowing, DAS; tasseling, 60 DAS; and harvest, 115 DAS) showed that leaf, stem, root N accumulation and total soil N were significantly increased under Deep band than under both Side band and Broadcast at N150P60, N187P60, N150P75 and N187P75, but not at N112P45, N150P45, N187P45, N112P60 and N112P75. Significantly greater leaf, stem, and root N accumulations were also displayed at N150 and N187 than at N112 for the same P60 or P75 under Deep band at 60 DAS and 115 DAS, while were for leaf and stem N accumulations at P75 and P60 than at P45 for the same N150 under Deep band at 45 DAS, 60 DAS and 115 DAS. Significantly greater agronomy N use efficiency, partial factor productivity and N use efficiency exhibited under Deep band than under Side band and Broadcast at N150P75 and N187P75, but at N150P60 and N187P60 for NUE only. In addition, leaf, stem, seed, root N concentrations positively correlated with their own N accumulations or soil N concentration at tasseling and harvest stages. Our results demonstrate that a synchronized N150P60, N187P60, N150P75 or N187P75 fertilization rate with Deep band placement can improve soil N availability and root N uptake, and hereby greater aboveground N accumulation, N use efficiency and yield production of maize particularly practical for small-holder farmers globally.

Many biological functions of curcumin have been reported. As certain bioactivities of curcumin are eliminated by antioxidants, reactive oxygen species generated by curcumin have been suggested as a relevant mechanism. In the present study, effects of different types of antioxidants on stability and bioactivities of curcumin were analyzed. High concentrations (>4mM) of the thiol antioxidants including N-acetylcysteine (NAC), glutathione (GSH) and β-mercaptoethanol accelerated decomposition of curcumin and other curcuminoids; Submillimolar levels (<0.5 mM) of GSH and NAC rather improved their stability. Ascorbic acid or superoxide dismutase also stabilized curcumin regardless of their concentration. Cellular levels and bioactivities of curcumin including cytotoxicity and induction of heme oxygenase-1 were significantly reduced in the presence of 8 mM of GSH and NAC. The effects were enhanced in the presence of submillilmolar GSH and NAC, or non-thiol antioxidants. The present results indicate that antioxidants with reduced thiol group could directly interact with α, β-unsaturated carbonyl moiety of curcuminoids and modulate their stability and bioactivity.

Sewage sludge is an organic waste generated in waste-water treatment plants with certain content of nutrients, what may potentially be used as a source of slow release fertilizer, especially as phosphorus (P) source, but it demands some pre-treatment and the content of P is much lower compared to soluble mineral fertilizers. For these reasons, composted sewage sludge was used to manufacture pelletized organomineral fertilizers, mixing it with the inorganic sources monoammonium phosphate (MAP) and AshDec® (ASD) (thermochemically incinerated sewage sludge). The fertilizers were physiochemically characterized and evaluated as to the dynamics of soil P solubilization, and the forms of P remaining according to its lability. The sources evaluated were: organic compost of sewage sludge powder (SSC), pelletized SSC (SCP), pelletized organominerals SSC+MAP (S+MAP) and SSC+ASD (S+ASD), ASD alone, all compared to a soluble mineral fertilizer (MAP), and a control without P fertilizer. A test was conducted in leaching columns with 50 g of soil (Oxisol), where the fertilizers were applied at a dose of 100 mg P/column, and 30 mL of water or 2% citric acid were added daily for 30 consecutive days. The collected leachates had pH measured and P content determined. Pelletizing process resulted in denser products and promoted more gradual P release. The organomineral S+MAP was the most water-soluble recycled source, solubilizing about 70% of the total P, while the others presented much lower solubilization (&lt;20%). In contrast, all fertilizers showed high solubility in 2% citric acid (except for S+ASD). After leaching, the greatest amount of P remaining in the soil as labile and moderately labile. Composting and the AshDec process produced materials with slow P solubilization, which would be favoured to solubilize in acidic soils and acidic rhizosphere conditions. In turn, the organomineral mixture of SSC with a highly soluble mineral fertilizer (MAP) resulted in a promising product with intermediate nutrient solubility, better synchronized with crop demand, thus increasing efficiency in P use.

Following on from work already carried out in our laboratory on a new biomass-derived green solvent, eucalyptol, we are now turning our attention to sabinene as a new green solvent. Sabinene is also derived from biomass. We have shown that it can be used as such or distilled to synthesize thiazolo[5,4-b]pyridine heterocycles by thermal or microwave activation. This new solvent was compared with various conventional and green solvents. The conditions were optimized to enable us to carry out the syntheses in good yields, and we were able to show that sabinene, a natural bicyclic monoterpene, could be used effectively as a solvent.

Microwave absorbers with lightweight, good stability and high efficiency have attracted much attention for their applications in many contemporary fields. In this work, the 3D porous (Ni@NO-C)n/NO-C composite absorber was prepared by a wet chemistry method with Ni chains and melamine as precursors, in which NO-C (N,O-doped carbon) encapsulated Ni particles are homogenously dispersed in the 3D porous networks of NO-C in the form of (Ni@NO-C)n chains. The special microstructure of the as-prepared material is proved to be benefit for the improvement of its microwave adsorption performance. The as-synthesized (Ni@NO-C)n/NO-C composite ab-sorber exhibited an effective absorption bandwidth of 4.1 GHz and an extremely large reflection loss of -72.3 dB. The excellent microwave absorbing performances can be ascribed to the coopera-tive consequence of dielectric loss and magnetic loss along with the balance between attenuation capability and impedance match.

Due to the low content, few studies are focused on the essential oils (EOs) of Phlomoides rotata (Benth. ex Hook. f.) Mathiesen (syn. Lamiophlomis rotata (Benth.) Kudô. This plant has been used to treat rheumatic arthritis and grasserie in China. However, such EOs may have important pharmacological activities such as anti-cancer. To identify the chemical markers (CM) in the EOs and evaluate their antioxidant activities (AAs), we firstly conduct a thoroughly investigation on their chemicals and AAs, to the best of our knowledge. Light yellow EOs with fresh and elegant smell are obtained by hydro-distillation with average yield 0.11% (volume mL/weight g). The crystals are separated from the EOs through cryoprecipitation, respectively. A total of 81 components are qualified and quantified in the EOs, crystals and EOs removed crystals, in which 44 ones are first reported. As for content, the main compounds are long-chain fatty acids (FAs) and their esters. The most abundant one n-hexadecanoic acid (palmitic acid, PA) accounting for 43.15-54.8%, 58.49-64.57% and 15.9-41.1%, in the EOs, crystals and EOs removed crystals, respectively. Seven compounds including PA, tetradecanoic acid, linoleic acid, oleic acid, methyl hexadecanoate, hexahydrofarnesyl acetone and phytol can be chosen a the CMs in these EOs. The AAs are evaluated through in vitro assays. PA presents pro-oxidant activities in a concentration dependence manner. Usually, the EOs removed crystals demonstrate stronger AAs, and the crystals demonstrate weaker AAs compared with that of the corresponding EOs, which is related to the different content of PA in these samples. This study can give some hints for the utilization of such EOs which are abundant in FAs such as PA.

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

Glioblastoma (GBM) is an aggressive and lethal primary brain tumor with restricted treatment options and a dismal prognosis. Oncolytic virotherapy (OV) has developed as a promising approach for GBM treatment. However, reaching invasive GBM cells may be hindered by tumor-surrounding, non-neoplastic cells when the OV is applied intratumorally. In this study, using a rodent GBM model and immunofluorescence analyses, we investigated the intranasal delivery of the oncolytic adenovirus (OAV) XVir-N-31 via virus-loaded, optimized shuttle cells. Intranasal administration (INA) was selected due to its non-invasive nature and the potential to bypass the blood-brain barrier (BBB). Our findings demonstrate that INA of XVir-N-31 loaded shuttle cells successfully delivers OAVs to the core tumor and invasive GBM cells, significantly prolongs the survival of GBM bearing mice, induces immunogenic cell death and finally reduces tumor burden, all this highlighting the therapeutic potential of this innovative approach. Overall, this study provides compelling evidence for the effectiveness of INA of XVir-N-31 via shuttle cells as a promising therapeutic strategy for GBM. The non-invasive nature of INA of OV-loaded shuttle cells holds great promise for future clinical translation. However, further research is required to assess the efficacy of this approach to ultimately progress in human clinical trials.

Nodule bacteria (rhizobia) represent a suitable model to address a range of evolutionary prob-lems including the tradeoff between genetic polymorphism and natural selection. Rhizobia possess the complicated genomes in which symbiotically specialized (sym) genes differ in their natural histories from core genes encoding for housekeeping functions. Diversification of sym genes is responsible for the rhizobia microevolution which depends on the host-induced natural selection. For the rhizobia speciation, diversification of core genes is responsible for which the selective factors are unclear. In this paper we demonstrate that in the goats’ rue rhizobia (Neorhizobium galegae) populations collected at North Caucasus and composed of two host-specific biovars orientalis and officianalis (N2-fixing symbionts of Galega orientalis and G. officinalis, respectively), evolutionary mechanisms are different for core and sym genes. In both N. galegae biovars, core genes are more polymorphic than sym genes. In bv. orientalis, evolution of core genes occurs under the impacts of driving se-lection (dN/dS > 1), while evolution of sym genes is close to neutral (dN/dS ≈ 1). In bv. officinalis, evolution of core genes is neutral, while for sym genes, it is dependent on purifying selection (dN/dS < 1). A marked phylogenetic congruence of core and sym genes revealed using the ANI analysis may be due to a low intensity of gene transfer within and between N. galegae biovars. Polymorphism of both gene groups and the impacts of driving selection on the core gene evolu-tion are more pronounced in bv. orientalis than in bv. officianalis reflecting the diversities of re-spective host plant species. In bv. orientalis, highly significant (P0 < 0,001) positive correlation was revealed between the p-distance and dN/dS values for core genes, while in bv. officinalis this cor-relation is lowly significant (0,05 < P0 < 0,10). For sym genes, correlation between the p-distance and dN/dS values is negative in bv. officinalis but is not revealed in bv. orientalis. These data along with the functional annotation of core genes implemented using the Gene Ontology tools sug-gests that evolution of bv. officinalis is based mostly on adaptation for in planta niches while in bv. orientalis evolution presumable depends on adaptation for soil niches. New insights into the tradeoff between natural selection and genetic diversity are presented suggesting that the gene polymorphism may be extended by driving selection only in the ecologically versatile organ-isms capable to support a broad spectrum of gene alleles in their genepools.

In this paper we study a special kind of finite mixture model. The sample drawn from the model consisits of three parts. The first two parts are drawn from specified distributions f1 and f2, while the third one is drawn from the mixture. A problem of interest is whether the two distributions f1 and f2 are the same. To test this hypothesis, we first define the regular location and scale family of distributions and assume that f1 and f2 are regular denisty functions. Then the hypothesis transforms to the equalities of the location and scale parameters, respectively. To utilize the information in the sample, we use Bayes’ theorem to obtain the posterior distribution and give the sampling method. Then we propose the posterior p-value to test the hypothesis. The simulation studies show that our posterior p-value largely improves the power in both normal and logistic cases while nicely controls the Type-I error. A real halibut dataset is used to illustrate the validity of our method.

In recent years, numerous approaches have been developed to comprehend the molecular altera-tions underlying thyroid cancer (TC) oncogenesis and explore novel therapeutic strategies for TC. It is now well established that the neurokinin-1 receptor (NK-1R) is overexpressed in cancer cells and that NK-1R is essential for viability of cancer cells. The binding of substance P (SP) to NK-1R in neoplastic cells plays a pivotal role in cancer progression by promoting neoplastic cell growth, protecting tumour cells from apoptosis, triggering invasion and metastasis through enhanced migration of cancer cells, and stimulating endothelial cell proliferation for tumour angiogenesis. Remarkably, all types of human TC (papillary, follicular, medullary, anaplastic), as well as met-astatic lesions, exhibit overexpression of SP and NK-1R compared to the normal thyroid gland. TC cells synthesize and release SP, which exerts its multiple functions through autocrine, para-crine, intracrine, and neuroendocrine processes, including the regulation of tumour burden. Con-sequently, the secretion of SP from TC results in increased SP levels in plasma, which are signifi-cantly higher in TC patients compared to controls. Additionally, NK-1R antagonists have demonstrated a dose-dependent antitumour action. They impair cancer cell proliferation on one side and induce apoptosis of tumour cells on the other side. Furthermore, it has been demonstrat-ed that NK-1R antagonists inhibit neoplastic cell migration, thereby impairing both invasiveness and metastatic abilities, as well as angiogenesis. Given the consistent overexpression of NK-1R in all types of TC, targeting this receptor represents a promising therapeutic approach for TC. Therefore, NK-1R antagonists, such as the drug aprepitant, may represent novel drugs for TC treatment.

Fifty-two kinds of N’-phenylhydrazides were successfully designed and synthesized. Their anti-fungal activity in vitro against five strains of C. alb. was evaluated. All prepared compounds owned varying degrees of activity and their MIC80, TAI, and TSI values were calculated. The in-hibitory activities of 27/52 compounds against fluconazole-resistant fungi C. alb. 4395 and C. alb. 5272 were much higher than those of fluconazole. The MIC80 values of 14/52 compounds against fluconazole-resistant fungus C. alb. 5122 were less than 4 μg/mL, so it was the most sensitive fungus (TSIB = 12.0). A11 showed the highest inhibitory activity against C. alb. SC5314, 4395, and 5272. The antifungal activities of B14 and D5 against four strains of fluconazole-resistant fungi were higher than those of fluconazole. The TAI values of A11 (2.71), B14 (2.13), and D5 (2.25) are the highest. Further exploring the antifungal mechanism revealed that the fungus treated with compound A11 produced free radicals and reactive oxygen species, and their mycelium mor-phology was damaged. In conclusion, the hydrazide scaffold showed potential in the develop-ment of antifungal lead compounds. Among them, A11, B14, and D5 demonstrated particularly promising antifungal activity and hold potential as novel antifungal agents.

Throughout this paper, we will establish a comprehensive theoretical foundation and rigorously develop the methodology to investigate the structure of quotient ring S/P under the influence of symmetric generalized n-derivations, where S represents an arbitrary ring, and P signifies a prime ideal of S satisfying certain algebraic identities acting on prime ideal P without relying on the assumption of primeness or semi-primeness of the ring.

Motivation: It is essential for the diagnosis and treatment of renal cancers to segment kidney tumours precisely and effectively. In medical image segmentation tasks, deep learning models have demonstrated promising results, and the UNet model is widely employed in this field. However, optimising the UNet model for kidney tumour segmentation further can improve its efficacy and deployment feasibility. Related Works: Previous works have explored various techniques to improve the efficiency of deep learning models in medical image segmentation. Image partitioning methods divides the input image into smaller regions, enabling parallel processing and reducing memory requirements. Pruning techniques eliminates redundant or insignificant weights, neurons and connections, resulting in a more compact and efficient model architecture. However, the UNet model architecture and its complexity in the context of kidney tumor segmentation using UNet remains unexplored. Methodology: The proposed methodology consists of adaptive partitioning and weight pruning. Adaptive partitioning divides the UNet model into smaller sub-models, facilitating parallel processing and accelerating inference without compromising segmentation accuracy. Weight pruning techniques remove redundant or less significant weights from the UNet-P model, reducing complexity and improving inference time by eliminating unnecessary computations. The adaptive partitioning and weight pruning processes are seamlessly integrated within the UNet-P architecture, resulting in an optimized model for kidney tumor segmentation. Results: We performed experiments utilising a dataset of KiT 23 CT scan images containing images of kidney malignancies. Compared to the standard UNet model, the optimised UNet-PWP model with adaptive partitioning and weight pruning obtained significant efficiency gains. The adaptive partitioning permitted parallel computation of sub-models, which accelerated inference times. Weight pruning decreased the UNet-PWP model’s complexity without compromising segmentation accuracy, thereby enhancing efficiency. The results of our experiments demonstrated the efficacy of the proposed method with 98% accuracy, demonstrating its potential for deployment in health sector.

The role of biomarkers in the diagnosis of inflammatory bowel disease is not fully characterized. C-reactive protein has a short half-life and elevates quickly after the onset of an inflammatory process, the performance is better in Crohn’s disease than in ulcerative colitis. Erythrocyte sedimentation rate is easy to determine, widely available, and cheap but the long half-life the influence of age, anemia, smoking, and drugs limit its usefulness. Fecal markers have good specificity, but suboptimal accuracy. Microbial antibodies and novel immunological markers show promise but need further evidence before entering clinical practice. Proteomic methods could represent the dawn of a new era of stool protein/peptide biomarker panels able to select patients at risk of inflammatory bowel disease.

Bimetallic (or multimetallic) catalysis has emerged as a powerful tool in modern chemical synthesis, offering improved reaction control and versatility. This review focuses on the recent de-velopments in bimetallic sequential catalysis for the synthesis of nitrogen heterocycles, essential building blocks in pharmaceuticals and fine chemicals. The cooperative action of two (and sometimes more) different metal catalysts enables intricate control over reaction pathways, enhancing selectivity and efficiency of N-heterocyclic compounds synthesis. By activating less reactive substrates, this multimetal catalytic strategy opens new synthetic possibilities for challenging compounds. The use of catalytic materials in bimetallic systems reduces waste and improves atom efficiency, aligning with green chemistry principles. With a diverse range of metal combinations and reaction conditions, bimetallic catalysis provides access to a broad array of N-heterocyclic compounds with various functionalities. This paper highlights the significant progress made in the past decade in this topic, emphasizing the promising potential of bimetallic catalysis in drug discovery and the fine chemical industries.

Deep ultraviolet (DUV) light emitting diode (LED) at emission wavelength of 254 nm is inevitable to replace the conventional toxic mercury UV Lamp as demanded by Minamata Convention of 2020. Both the conventional DUV LEDs (C-LED) and tunnel junction (TJ)-based UVC LEDs are suffering from high operating voltages, low hole injection efficiency and efficiency droops. Therefore, p-AlGaN and n-AlGaN layers-based TJ is one of the most promising parts of optical devices and has been widely utilized as carrier tunneling in DUV LEDs to mitigate both the contact resistance for Ohmic contact and low hole injection efficicny at 254 nm emission. Here an approach is presented to electrically manipulate the quantum tunneling probability by exploiting the transported carriers at the interface of n-AlGaN/p-AlGaN TJ with moderate Si and Mg-doping levels and optimized thickness. As a result, the Augur recomination rate was sucesfully suppressed and quite high radiative recombination rates were achived in the 254nm TJ-based DUV LEDs, which is attributed the improved holes injection toward the MQWs when compared to C-LED. The internal-quantum efficiency (IQE) of approximately ~ 88% in the TJ-based LED with zero efficiency droop is achived, which is 1.3 times greater than the IQE of approximately ~ 66% in the C-LED with efficiency droop of 53%. Based on our known knowledge, this is the highest reported IQE (88%) at emission wavelength of 254 nm in the AlGaN TJ-based LED with efficiency droop of 0%. It was found that the light output powers (LOP) of TJ-LED increases linearly under the varying current density, whereas in the case of C-LED the LOP changes nonlinearly under varying current density. This is attributed to the lower Augure recombination rate in the MQWs of TJ-based DUV LED. The operating voltages were remarkable reduced from 20 V to 5.4 V under 200 mA operation, which is attributed to the thickness and doping optimization in TJ and better selection of realively lower Al-content in the contact-layer. The demonstrated TJ-based DUV LEDs opens the door to epitaxial growth of high-performance UV emitters in MOCVD and MBE for a plethora of biomedical applications.

Antimicrobial peptides provide a powerful toolkit for combating multidrug resistance. Combatting eukaryotic pathogens is complicated by the fact, the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria, (symbionts of entomopathogenic nematode species), release a series of non-ribosomal templated antimicrobial peptides, some may be potential drug candidates. The ability of an entomopathogenic nematode /entomopathogenic bacterium symbiotic complex to survive in a given polyxenic milieu is a coevolutionary product, explaining that those gene complexes which are responsible for the biosynthesis of different non-ribosomal templated antimicrobial protective peptides (including those which are potently capable to inactivate the protist mammalian -pathogen Leishmania and the gallinaceous bird pathogen Histomonas) are co-regulated. Our approach is based on comparative antimicrobial bioassays of the culture media of the wild-type and regulatory mutant strains. We concluded that Xenorhabdus budapestensis and X. szentirmaii are excellent sources of non-ribosomal templated antimicrobial peptides, that are efficient antagonists of the mentioned pathogens. Data on selective cytotoxicity of different cell-free culture media encourages us to forecast that the recently discovered “easy-PACId” research strategy is suitable for constructing EPB strains producing and releasing single, harmless, non-ribosomal templated antimicrobial peptides with considerable drug, (probiotic) -candidate potential.

The N-acylhydrazone function has been reported as a pharmacophore group of molecules with diverse pharmacological activities, including anti-inflammatory effects. Thus, this study evaluated the anti-inflammatory potential of the compound N'-(3-(1H-indol-3-yl)benzylidene)-2-cyanoacetohydrazide (JR19) in vivo. The study started with the carrageenan-induced peritonitis model, followed by an investigation of leukocyte migration using the subcutaneous air pouch test and an assessment of the antinociceptive profile using formalin-induced pain. To find out the likely mechanism of action, a preliminary molecular docking study was performed focusing on the crystallographic structures of NFκB, iNOS, and sGCs. The computational study revealed satisfactory interaction energies with the selected targets, and the same peritonitis model was used to validate the involvement of the nitric oxide pathway and cytokine expression in the peritoneal exudate of mice pretreated with L-NAME or methylene blue. In the peritonitis assay, JR19 (10 and 20 mg/kg) reduced leukocyte migration by 59% and 52%, respectively, compared to the control group, with the 10 mg/kg dose used in subsequent assays. In the subcutaneous air pouch assay, the reduction in cell migration was 66%, and the response to intraplantar formalin was reduced by 39%, particularly during the inflammatory phase, suggesting that the compound lacks central analgesic activity. In addition, a reversal of the anti-inflammatory effect was observed in mice pretreated with L-NAME or methylene blue, indicating the involvement of iNOS and sGC in the anti-inflammatory response of JR19. The compound effectively and significantly decreased the levels of IL-6, TNF-α, IL-17, and IFN-γ, and this effect was reversed in animals pretreated with L-NAME, supporting a NO-dependent anti-inflammatory effect. In contrast, pretreatment with methylene blue only reversed the reduction in TNF-α levels. Therefore, these results demonstrate the pharmacological potential of the novel N-acylhydrazone derivative, which acts through the nitric oxide pathway and cytokine signaling, making it a strong candidate as an anti-inflammatory and immunomodulatory agent.

Japanese pepper (sansho, Zanthoxylum piperitum) contains several types of sanshools belonging to N-alkylamides. Because of long-chain unsaturated fatty acids present in their structure, sanshools are prone to oxidative deterioration, which poses problems in processing. Here, we evaluated the effects of antioxidants from the genus Zanthoxylum in preventing sanshool degradation using accelerated tests. An ethanolic extract of segment membranes of the sansho fruit pericarp was incubated at 70 °C for 7 days with different antioxidants to determine the residual amount of hydroxy-α-sanshool (HαS) in the extract. α-Tocopherol (α-Toc) showed excellent HαS-stabilizing activity at low concentrations. Among phenolic acids, we noted that the HαS-stabilizing activity increased with the number of hydroxy groups per molecule. For example, gallic acid and its derivatives exhibited excellent sanshool-stabilizing activity. Quercetin was found to be a superior HαS stabilizer compared with hesperetin and naringenin. However, the effective concentration was much higher for phenolic compounds than for α-Toc. These substances are believed to play a role in preventing the decomposition of sanshools in the pericarp of sansho. These sanshool stabilizers should be useful in the development of new beverages, foods, cosmetics, and pharmaceuticals that take advantage of the taste and flavor of sansho.

N-Acetyl-L-glutamate kinase (NAGK) catalyzes the rate-limiting step in the ornithine/arginine biosynthesis pathway in eukaryotic and bacterial oxygenic phototrophs. NAGK is the most highly conserved target of the PII signal transduction protein in Cyanobacteria and Archaeplastida (red algae and Chlorophyta). However, yet there is still much to be learnt on how NAGK is regulated in vivo. The use of unicellular green Chlamydomonas reinhardtii as a model system has already been instrumental in identifying several key regulation mechanisms that control nitrogen (N) metabolism. With a combination of molecular-genetic and biochemical approaches, we show the existence of the complex CrNAGK control at transcriptional level, which is dependent on N source and N availability. In growing cells, CrNAGK requires CrPII to properly sense the feedback inhibitor arginine. Moreover, we provided primary evidence that CrPII is only partly responsible for regulating CrNAGK activity to adapt to changing nutritional conditions. Collectively, our results suggest that in vivo CrNAGK is tuned at transcriptional and post-translational levels, and CrPII and additional as yet unknown factor(s) are integral parts of this regulation.

The development of good conductivity p-type β-Ga2O3 is critical to realize its devices and applications. The nitrogen-doped p-type β-Ga2O3 films with enhanced conductivity characteristics were prepared through the thermal oxidation of GaN in the N2O atmosphere. Further measurements were performed on the oxidized films at 1000, 1050, and 1100 °C to have insight into the underlying mechanism of the thermally activated transformation process. The room temperature photoluminescence (PL) spectra demonstrated a moderate ultraviolet emission peak at 246 nm, confirming the generation of gallium oxide with a band gap of ~5.0 eV. The normalized X-ray diffraction (XRD), the high-resolution transmission electron microscopy (HRTEM), and the selected area electron diffraction (SAED) patterns were used to confirm the characteristic of polycrystalline and anisotropic growth. Then, the effects of the oxidation temperature on the amount of incorporated nitrogen were analyzed using secondary ion mass spectrometry (SIMS). Moreover, the ionization energy of the acceptor of films oxidized at 1000, 1050, and 1100 °C was calculated and analyzed using the temperature-dependent Hall test results. The results showed that nitrogen doping was the main contributor to p-type electrical properties. The activation energy of the polycrystalline β-Ga2O3 prepared through thermal oxidation of GaN in the N2O atmosphere was estimated to be 147.175 kJ·mol-1 using the Arrhenius plot, which was considerably lower than that of both dry and wet oxidations of GaN in O2 ambient, thus confirming the efficiency of thermal oxidation of GaN in N2O.

Electrocardigraphy remains as a first-line evaluation method for cardiac function, recording the electrical activity of the heart from the body surface. Since atrial activation is seen on the ECG as P-wave, several factors are known to impact the appearance of the P-wave, such as direction of electric impulse, conduction abnormalities and anatomical characteristics of the atria. The aim of this retrospective study was to find statistically significant associations between anatomy of pulmonary veins (PVs) osberved in cardiac computed tomography (CT) and P-wave appearance during sinus rhythm on resting ECG. For each patient, a resting 12-lead ECG was recorded, the field of analysis was P wave – its’ duration, morphology and axis. The evaluation of the CT scan recordings was performed by creating 3D models of the left atrium and analyzing anatomy of the PVs and left atrial appendage (LAA). Noteworthy correlations were found: anatomy of the left PVs showed an association with LAA volume, LAA morphology and P-wave notching in lead II. The right PVs demonstrated relation with P wave axis and amplitude. Although these correlations cannot be classified as strong, they may play a role in significant scientific discoveries in future research projects.

Background: Hypovitaminosis D is a public health problem due to its implications for various diseases. Vitamin D has numerous functions, such as modulating the metabolism of some cellular tissues, and is expressed through the VDR gene that may influence gene expression modulation, which plays an important role in vitamin D metabolism. Objective: To evaluate the effect of the genotypes of single nucleotide polymorphism (SNP) BsmI of the vitamin D receptor (VDR) gene on VDR, SOD2, and CYP24A1 gene expression in individuals with low serum vitamin D levels. Methods: This was a cross-sectional analytical study. Individuals were invited to participate and, after signing the informed consent form, answered a structured questionnaire with identification data. Blood was collected for biochemical analysis, and vitamin D was measured by chemiluminescence; BsmI polymorphism was determined using real-time polymerase chain reaction (PCR) assays with TaqMan allelic discrimination, and gene expression was conducted by qRT-PCR using QuantiFast SYBR® Green PCR Master Mix. Data were analyzed using the SPSS 20.0 software, and differences were considered significant at p&lt;0.05. Results: 98 individuals with vitamin D ≤20 ng/dL were evaluated, and the SNP BsmI of the VDR gene showed CYP24A1 overexpression and low SOD2 expression. Conclusion: SNP Bsm I of the VDR gene can modulate the expression of the genes evaluated without interfering with serum levels.

The aim of this systematic review is to describe and to identify prospect of β-Tricalcium Phosphate (β-TCP) as Alveolar Bone Grafting (ABG) in Cleft Lip/Palate (CL/P) or alveolar bone cleft defect. A systematic review protocol based on Preferred Reporting Items for Systematic Reviews and Meta Analyses 2020 (PRISMA 2020) was drafted. The literature search was conducted with MEDLINE/PubMed, Web of Science/ ISI-Web of Knowledge, Scopus and Cochrane Library with English language and no publication year limits. The keywords yielded a total of 5824 publications. There are 3196 suitable articles to evaluate after removing duplicates and languages. Afterward, 1315 studies left after doing title and abstract reading. In addition, 85 full-articles were assessed for eligibility. The read the complete texts of those papers and eventually chose 20 that matched the inclusion requirements. Thirteen of the twenty studies included in this systematic review had a low risk of bias, one had a high risk of bias, and six had moderate bias which not report the randomization. β-TCP as ABG is biocompatible, visible and practical, offers a less invasive procedure, and does not interfere with orthodontic treatment. β-TCP as synthetic ABG can be the alternative to autologous bone grafts with several terms and conditions. Improvement of β-TCP efficacy for ABG in CL/P or alveolar bone cleft defects can be done by a tissue engineering approach combining β-TCP with growth factor, mesenchymal stem cells, or other graft materials and modification of β-TCP physical properties.

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

Systematic results of lattice dynamical calculation are reported for the novel (SiC)m/(GeC)n superlattices (SLs) by exploiting a modified-linear chain model (M-LCM) and a realistic rigid-ion- model (RIM). By employing the bond polarizability method in the framework of M-LCM, we have simulated Raman intensities for the graded (SiC)10-D/(Si0.5Ge0.5C)D/(GeC)10-D/(Si0.5Ge0.5C)D SLs by carefully integrating interfacial layer thickness D (≡ 0, 1, 2, 3 monolayers (MLs)). The variation of D has initiated considerable up (down) shifts of GeC-, (SiC)-like Raman peaks in the middle of the optical phonon frequency region. With D = 3 MLs, the maximum energy shift (by ~ 47 cm-1) of SiC-like modes has caused substantial changes in the Raman intensity profiles linked to the localization of atomic displacements at the interfacial transition regions. This effect can be considered as a vital tool for authenticating the interfacial structures in technologically important SLs. By using a RIM, we have reported SL phonon dispersions along the growth [001] as well as in the plane [100], [110] perpendicular to the growth. Our simulations of phonons in the acoustic mode region have not only confirmed the formation of minigaps at the zone center and zone edges but also provided evidence of anti-crossing and phonon confinement. Besides examining angular dependence of zone-center optical modes, we have also discussed phonon folding, confinement and anisotropic behavior in (SiC)m/(GeC)n SLs.

Silica aerogels and their derivatives have outstanding thermal properties with exceptional values in the thermal insulation industry. However, the brittle nature restricts its large-scale commercialization. Thus, enhancing their mechanical strength without affecting their thermal insulating properties is essential. Therefore, for the first time, highly thermally stable Poly(acrylamide-Co-acrylic acid) partial sodium salt is used as a reinforcing polymer to synthesize hybrid P(AAm-CO-AAc)-silica aerogels via epoxy ring-opening polymerization in the present study. Functional groups in P(AAm-CO-AAc) partial sodium salts, such as CONH2 and COOH, acted as nucleophiles for the epoxy ring-opening reaction with (3-glycidyloxypropyl)trimethoxysilane, which resulted in a seven-fold enhancement in mechanical strength compared to that of a pristine silica aerogel while maintaining the thermal conductivity at less than 30.6 mW/mK and porosity of more than 93.68%. Moreover, the hybrid P(AAm-CO-AAc)-silica aerogel demonstrated improved thermal stability up to 343 ⁰C owing to the synergetic effect between P(AAm-CO-AAc) and the silica aerogel, corresponding to thermal stability and strong covalent bonding among them. These excellent results illustrate that this new synthetic approach for producing hybrid P(AAm-CO-AAc)-silica aerogels is useful for enhancing the mechanical strength of a pristine silica aerogel without impairing its thermal insulating property and shows potential as an industrial heat insulation material.

Since the first description of SARS-CoV-2 in China in 2019, thousands of variants have emerged worldwide. For some of them, the constellation of mutations caused changes in virus biology, pathogenicity, infectivityity and transmissibility resulting in dissemination throughout the world. Gamma variant (P.1) differs from SARS-CoV-2 Wuhan strain (B.1) by 12 amino acids in the Spike (S) protein, and presented mutations related to greater affinity for the receptor angioten-sin-converting enzyme 2 (ACE-2) and/or immune escape. The Gamma variant and subvariants were responsible for the second wave of COVID-19 in the Brazilian city of Manaus, characterized by high mortality and rapid transmission. The ability of variants to induce cytokine production may be closely related to their pathogenicity. Herein we observed that there was no significant difference in the quantity of cytokines among macrophages or neutrophils infected with P.1 and B.1 strains. Also, no significant difference was observed in the absolute number of macrophages and neutrophils infected with these variants. Furthermore, no evidence of SARS-CoV-2 replication was observed in macrophages when infected by the two analyzed variants. Our findings suggest that the difference in the epidemiological outcome observed during the P.1 variant spread when compared to B.1, it is not explained by differences in the quantity of cytokines and absolute number of macrophages or neutrophils. Through bioinformatics analysis of the S protein, we observed that the physicochemical differences between the variants and subvariants of P.1, probably refer to the degree of infectivity, due to the impact caused in the recognition of antibodies and receptor af-finity

Inhibition of quorum sensing (QS)-dependent biofilm formation and virulence is extensively investigated as a novel approach to combat bacterial pathogens by impeding their ability to cause antibiotic-tolerant diseases. Such strategies are considered a promising alternative to conventional antibacterial therapy since interrupting the central cell-to-cell communication system imposes less selective pressure on the target pathogen. In this study, novel hybrid compounds composed of anthranilic acids substituted with halogens at different positions of the phenyl ring, and 4-(2-aminoethyl/4-aminobuthyl)amino-7-chloroquinoline linked via 1,3,4-oxadiazole were synthesized using standard procedures. Their anti-QS activities were evaluated using Chromobacterium violaceum ATCC31532 (anti-biofilm and bactericidal activities) and Pseudomonas aeruginosa PAO1 (anti-biofilm/-virulence activities). The results showed that compounds 15–19 and 23 inhibited the production of violacein, the QS-inducible pigment, in C. violaceum to a similar extent as the model QS inhibitor - quercetin (83.5–90%). Compound 15 exhibited the strongest effect on P. aeruginosa in the anti-biofilm screening, reducing its ability to form biofilm by almost 50%, while compounds 16 and 19 were able to reduce the biofilm formation by approximately 30%. However, compound 23 did not demonstrate significant anti-biofilm activity and only inhibited pyocyanin production in P. aeruginosa. In conclusion, this study suggests that 1,3,4-oxadiazoles 15, 16, and 19 are the most promising compounds for future research as novel QS inhibitors against Gram-negative bacteria equipped with different QS signaling pathways.

The scope of this study was twofold: first, to introduce a new method in examining measurement invariance, especially with large-scale studies where a large number of group comparisons are involved: the alignment approach, where only configural invariance is necessary to achieve measurement invariance. Second, to evaluate the psychometric robustness of this approach using real-life data. Particularly, we applied this approach to examine whether the factor structure of a cognitive ability test (PGAT) exhibits measurement invariance across the 26 universities of the Kingdom of Saudi Arabia. The sample consisted of 9,849 graduate students from 26 universities around the Kingdom. The results indicated a robust configural model suggesting that the P-GAT subscales were invariant across the 26 universities. Finally, the aligned factor mean values were estimated, and factor mean comparisons of every group’s mean with all other group means were conducted for both cognitive domains (Verbal and Quantitative). In both domains, King Saud University had the highest mean score among all universities. Moreover, its mean factor score was significantly higher than any other university besides Dammam University. On the other hand, several universities allocated at the northern and Southern borders of the country exhibited the lowest factor mean scores.

Limited availability of expensive alloying elements elevates low-alloyed steels to a unique position in the field of lightweight construction and mass production. Quenching and partitioning (Q&P) heat treatments of low-alloyed steels with exceptional property combinations are particularly promising. In this study, we characterize for the first time a new low-alloyed steel to be processed by Q&P heat treatments. In combined experimental and numerical studies, we design a novel approach that effectively combines the short cycle times of press hardening with the excellent property profiles of Q&P-treated steels. We identify appropriate transformation parameters for Q&P heat treatments by dilatometric studies and we adjust a number of reference conditions with different isothermal holding times. By means of SEM analysis and XRD measurements, we show that different fractions of retained austenite result in different mechanical properties. Initial numerical designs of the process can identify varying temperature profiles and cooling rates depending on the position in the die. The results show that the geometry of the part plays a minor role, but the die temperature is the dominant factor for successful partitioning directly in the press hardening process.

Bimetallic Ni/Cu core-shell and Cu-Ni heterostructural micro- and nanoparticles were prepared using two simple successive reduction procedures. Monometallic Ni and Cu particles were synthesized for comparison. The phase constitutions and morphological features of the particles were studied by means of X-ray diffraction, energy-dispersive X-ray spectroscopy and scanning electron microscopy methods. All the obtained mono- and bimetallic particles were applied as electrocatalysts in the electrohydrogenation of p-nitrophenol (p-NPh). An additional electrochemical reduction of copper cations during the hydrogen saturation of Cu-containing particles was established. Some of the prepared particles exhibited high catalytic activity with an increase in the hydrogenation rate of p-NPh by more than 3 times compared to its electrochemical reduction on the non-activated cathode, and p-NPh conversion yielded the maximum values. The main product of p-NPh electrocatalytic hydrogenation over Ni-Cu particles is p-aminophenol, which is an intermediate in the synthesis of many drugs. p-Aminophenol formation is confirmed by UV-Vis spectra.

Several vaccines against COVID -19 have been developed and licenced to enhance the immune response against SARS-CoV-2. Similarly, infection with SARS-CoV-2 before vaccination has been shown to provide significant protection against severe infection and hospitalisation. The aim of this study was to investigate the effect of three doses of Sinopharm vaccine and SARS-CoV-2 infection on the specific immune response in 103 volunteers, measuring neutralizing antibodies, anti-S1 IgG, anti-RBD IgM, anti-N IgM, anti-N IgG antibodies and interferon γ. Our results showed that the presence of cardiovascular diseases increased the level of anti-N-IgG antibodies, while endocrinological diseases decreased the level of neutralizing antibodies and anti-N-IgG antibodies, suggesting that these diseases alter the effect of vaccine immunity. In addition, there was a significant decrease in anti-S1 IgG levels 6 months and in anti-N IgG levels 18 months post-infection, while neutralizing antibody and interferon γ levels were constant at 3, 6 and 18 months post-infection. Therefore, our results confirm the importance of hybrid immunity as the strongest and most durable compared to exclusively natural or vaccine-induced immunity. Significant positive correlations were found between humoral and cellular immunity markers: neutralizing antibodies, anti-S1 IgG, anti-N IgG and interferon γ, indicating a unique coordinated response specific to COVID-19.

Plant N concentration (PNC) has been commonly used to guide farmers in assessing maize (Zea mays L.) N status and making in-season N fertilization decisions. However, PNC varies based on the development stage and therefore a relationship between biomass and N concentration is needed (i.e., critical N dilution curves; CNDC) to better understand when plants are N deficient. A few CNDC have been developed and used for plant N status diagnoses, but have not been tested in the US Midwest. The objective of this study was to evaluate under highly diverse soil and weather conditions in the US Midwest the performance of CNDCs developed in France and China for assessing maize N status. Maize N rate response trials were conducted across eight US Midwest states over three years. This analysis utilized plant and soil measurements at V9 and VT development stages and final grain yield. Results showed that the French CNDC (y=34.0x-0.37, where y is critical PNC, x is aboveground biomass) was better with a 91% N status classification accuracy compared to only 62% with the Chinese CNDC (y=36.5x-0.48). The N nutrition index (NNI), which is the quotient of the measured PNC and the calculated critical N concentration (Nc), based on the French CNDC was significantly related to soil nitrate-N content (R2=0.38-0.56). Relative grain yield on average reached a plateau at NNI values of 1.36 at V9 and 1.21 at VT, but for individual sites ranged from 0.80 to 1.41 at V9 and from 0.62 to 1.75 at VT. The NNI threshold values or ranges optimal for crop biomass production may not be optimal for grain yield production. It is concluded that the CNDC developed in France is suitable as a general diagnostic tool for assessing maize N status in US Midwest. However, the threshold values of NNI for diagnosing maize N status and guiding N applications vary significantly across the region, making it challenging for guiding specific on-farm N management. More studies are needed to determine how to effectively use CNDC to make in-season N recommendations in the US Midwest.

To improve the understanding of soil–pile interaction of laterally loaded piles, the quasi-static test of pile group foundation in silty clay with 5 foundation piles arranged in cross shape is carried out. The direct measurement-based p–y curves at different depths showed nonlinear behavior, in which the initial stiffness and ultimate soil reaction increased as the depth increased. The loading displacement amplitude corresponding to the failure of each foundation pile in the high axial compression reinforced concrete pile group foundation is given as follows: the front-end nappe foundation pile (#3 pile) is 6mm, the middle pile is 16mm, the front-end nappe foundation pile is 20mm, and the loading displacement amplitude of side pile is 24mm. In silty clay, due to the existence of pile group effect, the edge effect has little effect on the horizontal foundation bed coefficient of foundation pile in pile group, while the influence of masking effect on the horizontal foundation bed coefficient of each foundation pile in pile group is not related to the position of pile, but only to the existence of masking effect, and the influence of different columns of masking effect on the horizontal foundation bed coefficient is the same.

Background The nematode Caenorhabditis elegans (C. elegans) possesses a sophisticated sense of smell and is used for a novel cancer screening test that utilizes the chemotaxis index. We designed a single-institution, prospective study to confirm the ability of Nematode Nose (N-NOSE) to determine preoperative chemotherapy's efficacy for esophageal cancer patients. Patients and Methods We investigated the predictability of N-NOSE screening for the clinical effects of preoperative chemotherapy for esophageal cancer patients receiving radical surgery. The index reduction score (IRS) was calculated by chemotaxis of C. elegans at three points: before treatment, before surgery, and after surgery, and its clinical relevance was examined. Result Thirty-nine patients with esophageal cancer were enrolled from August 2020 to December 2021 and 30 patients receiving radical surgery were examined. Complete response or partial response was achieved in 23 cases (76.7%). When the target of the treatment effect was complete response only, the prediction accuracies of the IRS calculated by area under the curve was 0.85 (95% Confidence interval: 0.62-1) in clinically achieving complete response group, and the sensitivity and specificity were 1 and 0.63, respectively. Conclusion Index reduction score using N-NOSE screening may reflect the efficacy of chemotherapy for esophageal cancer patients. A large-scale prospective study at multiple centers is desired in the future.

Much evidence reveals an important link between gut microbiota and the heart. In particular, the gut microbiota plays a key role in the onset of cardiovascular (CV) disease, including heart failure (HF). In HF, splanchnic hypoperfusion causes intestinal ischemia resulting in the translocation of bacteria and their metabolites into the blood circulation. Among these, the most important is the Trimethylamine N-Oxide (TMAO), which is responsible through various mechanisms for pathological processes in different organs and tissues. In this review, we summarise the complex interaction between gut microbiota and CV disease, particularly with HF, and the possible strategies to influence its composition and function. Finally, we highlight the potential role of TMAO as a novel prognostic marker and new therapeutic target of HF.

Duchenne muscular dystrophy (DMD), the severest form of muscular dystrophy, is characterized by progressive muscle weakness with fatal outcome most often before the fourth decade of life. Despite recent addition of molecular treatments, DMD remains a disease without a cure, and the need persists for the development of supportive therapies aimed to help improve patients’ quality of life. This review focusses on the therapeutical potential of amino acid and derivative supplements, summarizing results obtained in preclinical studies in the murine disease model. Several promising compounds have come forward, with L-arginine, N-acetylcysteine and taurine featuring among the most intensively investigated. Beneficial effects include improved muscle function and reduced muscle fiber necrosis and reduced inflammatory and oxidative damage to muscle tissues, however mild side effects have also surfaced. In order to identify amino acid formulae that are safe and of true benefit to DMD patients, more explorative, placebo-controlled and long-term clinical trials need to be conducted, documenting therapeutic outcomes.

The inability to efficiently metabolize homocysteine (Hcy), which occurs in nutritional and genetic deficiencies, leads to hyperhomocysteinemia (HHcy) thereby causing endothelial dysfunction, a hallmark of atherosclerosis which underpins cardiovascular disease (CVD). The dysregulation of mammalian target of rapamycin (mTOR) signaling, and impaired autophagy play important roles in CVD. Biochemically, HHcy is characterized by elevated levels of Hcy and its metabolites, Hcy-thiolactone (HTL) and N-Hcy-protein (N-Hcy). However, whether these metabolites can dysregulate mTOR signaling and autophagy in endothelial cells is not known. Here, we examined the influence of HTL, N-Hcy, and Hcy on the PHF8/H4K20me1/mTOR/autophagy pathway in human umbilical vein endothelial cells (HUVEC). We found that treatments with HTL, N-Hcy, or Hcy significantly reduced PHF8 protein and mRNA expression, increased H4K20me1, and upregulated mTOR signaling. Autophagy was also impaired (significantly downregulated BECN1, ATG5, ATG7, and LC3 protein and mRNA levels). We also found that these changes were mediated by PHF8-targeting microRNA (miR): miR-22-3p and miR-1229-3p. The effects of HTL, N-Hcy, or Hcy on the miR expression and on the PHF8/H4K20me1/mTOR/autophagy pathway were abrogated by treatments with an inhibitor of miR-22 or miR-1229. Taken together, these findings show that Hcy metabolites can upregulate miR-22-3p and miR-1229-3p expression, which then dysregulate the PHF8/H4K20me1/mTOR/autophagy pathway, important for vascular homeostasis.

Respiratory syncytial virus (RSV) RNA synthesis takes place in cytoplasmic viral factories also called inclusion bodies (IBs), which are membrane-less organelles concentrating the viral RNA polymerase complex. IBs assembly is driven by liquid-liquid phase separation promoted by interactions between the viral nucleoprotein N and the phosphoprotein P. We recently demonstrated that cyclopamine (CPM) inhibits RSV multiplication by disorganizing and hardening IBs. Although a single mutation in the viral transcription factor M2-1 induced resistance to CPM, the mechanism of action of CPM still remains to be characterized. Here, using FRAP experiments on reconstituted pseudo-IBs both in cellula and in vitro, we first demonstrated that CPM activity depends on the presence of M2-1 together with N and P. We show that CPM impairs the competition between P and RNA binding to M2-1. As mutations on both P and M2-1 induced resistance against CPM activity, we suggest that CPM may affect the dynamics of the M2-1−P interaction, thereby affecting the relative mobility of proteins contained in RSV IBs. Overall, our results reveal that stabilizing viral protein-protein interactions is an attractive new antiviral approach. They pave the way for the rational chemical optimization of new specific anti-RSV molecules.

The global malaria community has picked up the theme of malaria elimination in greater than 90 % of the world’s population in the next decade. The recent reports of P. vivax in all sub-Saharan Africa, including Duffy negative individuals, threaten the efforts to achieve elimination. This is not only in view of strategies that are tailored only to P. falciparum elimination, but also due to currently revealed biological characteristics of P. vivax concerning the relapse patterns of hypnozoites and conservation of a large biomass at cryptic sites in the bone marrow and spleen. A typical scenario has been observed in Botswana from the period between 2008 to 2018, which palpably projects how P. vivax could endanger efforts at malaria elimination where the two parasites co-exist. The need for the global malaria community, NMPs, funding agencies and relevant stakeholders to engage in a forum to discuss and recommend clear pathways for sub-Saharan Africa regarding malaria elimination including P. vivax, is warranted.

The mechanisms underlying the de novo regeneration of adventitious roots are still poorly understood, particularly in trees. In this study, we developed a system for studying different modulators of adventitious rooting (AR) at physiological and molecular levels by using for the first time leaves excised from chestnut microshoots. The rooting response of leaves was ontogenetic-stage dependent, and similar to that of the original microshoots. Initiation of root primordia and root development were inhibited by application of N-1-naphthyl-phthalamic acid (NPA), although the effect of this inhibitor of auxin polar transport (PAT) depended on the timing of application. Expression of CsSCL1, an auxin-inducible gene in juvenile and mature shoots during AR, was upregulated by auxin only in rooting-competent leaves during the novo root organogenesis and the expression was reduced by the NPA treatment. This inhibitory effect on gene expression was detected during reprograming of rooting competent cells towards root initials in response to auxin, indicating that PAT-mediated upregulation of CsSCL1 is required in the initial steps of AR in chestnut leaves. The localized expression of CsSCL1 in the quiescent center (QC) also suggests a role for this gene in the maintenance of meristematic competence and root radial patterning.

A simple and sensitive liquid chromatography-tandem mass spectrometry (LC– MS/MS) method has been developed for the simultaneous determination of atorvastatin (ATOR), ezetimibe (EZM) and their three metabolites including o-hydroxyl atorvastatin (o-OH ATOR), p-hydroxyl atorvastatin (p-OH ATOR), and ezetimibe-glucuronide (EZM-G) in human plasma using benzyl paraben (BP) as internal standard (IS). The analytes and IS were ionized using ESI positive ion mode (ATOR, o-OH ATOR, and p-OH ATOR), ESI negative ion mode (EZM, EZM-G, and BP), and operated in multiple reaction monitoring (MRM) mode. They were next extracted by salting-out assisted liquid–liquid extraction with acetonitrile, and then analyzed by liquid chromatography on a reversed-phase chromatographic column (50 mm × 4.6 mm; 3.5 µm), using a mixture of ac-etonitrile and an acetic acid solution (0.5%) as the mobile phase, showing high extraction effi-ciency (>70%), and a minimized matrix effect. The method was satisfactorily validated, and showed excellent linearity over wide concentration ranges of 0.06–15 ng/mL, 0.6–150 ng/mL, 0.4–100 ng/mL, 0.12–30 ng/mL, and 0.05–3 ng/mL for EZM, EZM-G, ATOR, o-OH ATOR, and p-OH ATOR, respectively.

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

In the present study we tested the effect of small molecular weight redox molecules on collagen-induced platelet aggregation. We used N-acetylcysteine amide (AD4), the amide form of N-acetylcysteine (NAC), a thiol antioxidant with improved lipophilicity and bio-availability compared to NAC, and the thioredoxin mimetics (TXM) peptides, TXM-CB3, TXM-CB13, and TXM-CB30. All compounds significantly inhibited platelet aggregation induced by collagen, with TXM-peptides and AD4 being more effective than NAC. The levels of TxB2 and 12-HETE, the main metabolites derived from the cyclooxygenase and lipoxygenase pathways following platelet activation, were significantly reduced in the presence of AD4, TXM-peptides, or NAC, when tested at the highest concentration (0.6 mM). The effect of AD4, TXM-peptides, and NAC was tested also on the clotting time (CT) of whole blood. TXM-CB3 and TXM-CB30 showed the highest increase of CT. Furthermore, two representative compounds, TXM-CB3, and NAC, showed an increase in the an-ti-oxidant free sulfhydryl groups of plasma detected by Ellman’s method, suggesting a contribution of plasma factors to the antiaggregating effects. Our results suggest that these small molecular weight redox peptides might become useful for the prevention and/or treatment of oxidative stress conditions associated with platelet activation.

Oestrogen receptor expression in breast cancer (BC) cells is a marker of high cellular differentiation and allows the identification of two BC groups (ER-positive and ER-negative) that, although not completely homogeneous, differ in biological characteristics, clinical behaviour and therapeutic options. The study, based on three publicly available EWAS datasets, focuses on the comparison between these two groups of breast cancer using an epimutation score. The score is calculated not only based on the presence of the epimutation but also on the deviation amplitude of the methylation outlier value. For each dataset, we performed a functional analysis based first on the functional gene region of each annotated gene (we aggregated the data per gene region TSS1500, TSS200, first-exon, body-gene identified by the information from the Illumina Data Sheet) and then we performed a pathway enrichment analysis through the REACTOME database based on the genes with the highest epimutation score. Thus, we blended our results and found common pathways for all three data sets. We found that a higher and significant epimutation score due to hypermethylation in ER-positive BC is present in the promoter region of the genes belonging to the SUMOylation pathway, the NOTCH pathway, the IFN-$\gamma$ signalling pathway and the deubiquitination protease pathway; while a higher and significant level of epimutation due to hypomethylation in ER-positive BC is present in the promoter region of the genes belonging to the ESR-mediated pathway. The presence of this state of promoter hypomethylation in the ESR-mediated signalling genes is consistent and coherent with an active signalling pathway mediated by oestrogen function in the group of ER-positive BC. SUMOylation and NOTCH pathways are associated with BC pathogenesis and have been found to play distinct roles in the two BC subgroups. We speculated that the altered methylation profile may play a role in regulating signalling pathways with specific functions in the two subgroups of ER-BC.

The aim of this work was to investigate a new, simple one-pot combustion synthesis technique for creating sulphur-based CuS/ZnS p-n heterojunction nanocomposite photocatalysts. The study examined the photocatalytic activity and reusability of these nanocomposites in removing rhodamine B (RhB) dye under visible light irradiation. Various methods of characterisation were employed to determine the properties of the materials, including particle morphology, crystalline phases and bandgap energy. The intrinsic reaction parameters, such as catalyst loading, pH level of the solution, and initial pollutant concentration, were varied to establish the optimal photo-degradation conditions. The results showed that a binary CuS/ZnS catalyst with a 10 gL-1 loading, at pH 5, degraded 97% of 5 ppm RhB dye after 270 minutes of visible light irradiation. Addition-ally, this composite catalyst exhibited excellent chemical stability and reusability, achieving 83% RhB dye removal after five recycling runs. Scavenger tests identified the photogenerated holes (h+) and superoxide free radicals (•O2) as the primary reactive species responsible for degradation. This study provides valuable insight into the design of highly efficient nanomaterials for removing organopollutants in wastewater, and a possible reaction mechanism is proposed.

Aberrant glycosylation affects cancer progression and immune evasion. Approximately 15% of colorectal cancers (CRCs) demonstrate microsatellite instability (MSI) and display major differences in outcomes and therapeutic responses as compared to corresponding microsatellite stable (MSS) tumors. We compared the N-glycan profiles of stage II and IV MSI CRC tumors, further subdivided into BRAFV600E wild-type and mutated subgroups (n=10 in each subgroup), with each other and with those of paired non-neoplastic mucosal samples using mass spectrometry. Further, the N-glycans of BRAFV600E wild-type stage II MSI tumors were compared to corresponding MSS tumors (n=9). Multiple differences in N-glycan profiles were identified between MSI CRCs and control tissues, as well as between stage II MSI and MSS samples. MSI CRC tumors showed a lower relative abundance of high-mannose N-glycans than the control tissues or the MSS CRCs. Among MSI CRC subgroups, acidic N-glycans showed tumor stage and BRAF mutation status dependent variation. Especially large, sulfated/phosphorylated, and putative terminal N-acetylhexosamine containing acidic N-glycans differed between the MSI CRC subgroups, showing opposite changes in stage II and IV, when comparing BRAF mutated and wild-type tumors. Our results show that molecular subgroups of CRC have characteristic glycan profiles that may explain certain carcinogenic properties of MSI tumors.

Panax ginseng C. A. Meyer (P. ginseng), has been widely used in traditional Chinese medicine (TCM). It contains a number of chemical components and possesses a variety of pharmacological activities. Alzheimer's disease (AD) is neurodegenerative disease that creates a huge burden on the lives and health of individuals. In recent years, studies have indicated that the chemical components of P. ginseng, especially ginsenosides, play a pronounced positive role in the prevention and treatment of neurological diseases. This review aimed to summarize currently studies on chemical components and the mechanisms action in AD intervention treatment of P. ginseng, especially ginsenosides. In this review, the components of P. ginseng and their respective active effects were first introduced. Then the key molecular mechanisms and signaling pathways of P. ginseng were introduced, and its different active ingredients in the prevention and treatment of Alzheimer's disease-related pathogenesis were also summarized from the pathogenesis of AD Aβ generation and aggregation, hyperphosphorylation of tau protein，oxidant stress，neuroinflammation，mitochondrial damage，disorder of neurotransmitter and gut microbiota. Signaling pathway networks related to the action of ginseng active ingredients was constructed, which could serve as a therapeutic target for Alzheimer's disease. In addition to a detailed report on P. ginseng in improving Alzheimer's disease-related pathogenesis, the application of the current technology, spatial metabonomics in AD therapeutics and diagnostics were later discussed. Spatial metabonomics could be applied to investigate the multi-target intervention of P. ginseng on Alzheimer's disease. Research perspectives for the study of P. ginseng in the treatment of Alzheimer's disease were provided for further studies.

J/ψ, a charmonium bound state made of a charm and an anti-charm quark, has been discovered in the 1970s and confirmed the quark model. Because the mass of charms quarks is significantly above the Quantum Chromodynamics (QCD) scale ΛQCD, charmonia are considered as excellent probes to test perturbative Quantum Chromodynamics (pQCD) calculations. Over the past decades, they have been studied extensively at different high energy colliders. However, their production mechanisms, which involves multiple scales, are still not very well understood. Recently, in high multiplicity p+p collisions at RHIC and at the LHC, a significant enhancement of J/ψ production yield has been observed, which suggests a strong contribution from the Multi-Parton Interaction (MPI). This is different from the traditional pQCD picture where charm quark pairs are produced from a single hard scattering between partons in p+p collisions. In this work, we will report the J/ψ normalized production yield as a function of normalized charged particle multiplicity over a board range of rapidity and event multiplicity in the J/ψ→μ+μ− channel with PHENIX Run 15 p+p data at \sqrt{s}=200 GeV. The results are compared with PYTHIA 8 simulations with the MPI option on and off. Finally, the outlooks of J/ψ in p+Au and Au+p collisions along with Color Glass Condensate (CGC) predictions and of multiplicity dependent ψ(2S)/J/ψ ratio in p+p data will be briefly discussed.

Rechargeable aqueous Zn-ion batteries (ZIBs) have attracted considerable attention owing to their high theoretical capacity of 820 mA h g‒1, low cost and intrinsic safety. However, the electrolyte leakage and the instability issues of Zn negative electrodes originating from side reactions between the aqueous electrolyte and Zn negative electrode, not only restricts the battery stability but also results in short-circuit of aqueous ZIBs. Herein we report a flexible and stable N-isopropylacrylamide/sodium alginate (N-SA) gel electrolyte, which possesses high mechanical strength and high ionic conductivity of 2.96×10‒2 S cm‒1, and enables the Zn metal negative electrode and MnO2 positive electrode to reversibly and stably cycle. Compared to the liquid electrolyte, the N-SA hydrogel electrolyte can effectively form a uniform Zn deposition and suppress the generation of irreversible by-products. The assemble symmetric Zn/Zn cells at a current density of 1 mA cm‒2 shows a stable voltage profile, which maintains a low level of about 100 mV over 2600 h without an obvious short circuit or any overpotential increasing. Specially, the assembled Zn/N-SA/MnO2 batteries can deliver a high specific capacity of 182 mAh g‒1 and maintain 98% capacity retention after 650 cycles at 0.5 A g‒1. This work provides a facile method to fabricate high-performance SA-based hydrogel electrolytes that illustrates their potential for flexible batteries for wearable electronics.

The use of nitrogen (N) fertilizers can have detrimental effects on the environment due to nitrate leaching. This study aims to examine the impact of N fertilizer source and application timing on wheat yield and nitrate leaching in various soil textures. A randomized complete block design (RCBD) was employed to conduct the experiment. The treatments consisted of two N fertilizer sources: ammonium nitrate (AN) and urea (NN), applied at three different times throughout the year, with a control treatment. The three application timings were total application before sowing (T₁), total application in spring (T₂), and half the amount before sowing and the other half in spring (T₃). The experiment was conducted in three different soil textures (sandy loam, silty clay loam, and silty clay), with three replications over three growing seasons: 2018-19 (Y₁), 2019-20 (Y₂), and 2020-21 (Y₃). The results indicated significant effects of different soil textures on grain yield. Specifically, the silty clay loam soil differed significantly from the sandy loam and silty clay soils in terms of grain yield. The interaction effects between the N fertilizer source and application timing were also found to be significant for all soil textures (p<0.01). In sandy loam and silty clay soils, the grain yield increased when using the T₃ application timing compared to the silty clay loam soil. Notably, the silty clay loam soil with the T₂ application timing exhibited the highest grain yield, with a yield of 6863.6 kg ha^-1. Furthermore, the study revealed that N fertilizers and their application timing significantly influenced the protein content in the silty clay and sandy loam soils. The protein percentages were 10.76 and 10.93 for the silty clay and sandy loam soils, respectively, following the T₂ treatment. Additionally, ammonium nitrate (AN) demonstrated a noticeable effect on the percentage of grain protein compared to urea (NN). In conclusion, the application timing of N fertilizers had an impact on grain yield and protein content in different soil textures. Moreover, nitrate concentration increased throughout the experiment, with the highest soil nitrate concentration observed in both fertilizer treatments, particularly in the sandy loam soil.

This paper proposes an AI-based approach to overcome the limitations of the SHM system in measuring global stress with limited sensors. Feature elements are selected based on correlation analysis among finite elements and used as stress-measured points. An ANN is used to establish the solution relationship between the feature and correlation elements. The proposed method is applied to the connector structure of an offshore platform, and an optimal ANN is established to optimize accuracy by considering factors like the number of sensors, neural network framework, and convergence criteria. The accuracy of the ANN is verified through a real-scale model test, demonstrating 93.6% accuracy. This technology represents a significant advancement, enhancing the practicality of the structural health monitoring (SHM) system from “point monitoring" to “field monitoring".

3,4-Dihydroquinolin-2(1H)-ones represent a class of valuable bioactive compounds with six-membered nitrogen-containing heterocyclic structures. The development of simple, mild and efficient synthetic methods has been widely concerned by synthetic chemists. In this review, we have summarized a series of different synthetic strategies for the synthesis of dihydroquinoline-2(1H)-ones via catalytic annulation of α,β-unsaturated N-arylamides in the past decade, including covering electrophilic cyclization, radical initiated cyclization and photochemical cyclization reactions. Besides, the substrate scope and mechanistic details are also discussed. This paper will provide a useful reference for the development of diverse synthesis methodologies of 3,4-dihydroquinolin-2(1H)-ones.

This study focuses on mimicking constitutive phosphorylation in the N-terminus of the myosin regulatory light chain (S15D-RLC) as a rescue strategy for the mutation-induced cardiac dysfunction in transgenic (Tg) models of restrictive (RCM) and dilated (DCM) cardiomyopathy caused by mutations in myosin essential (ELC) or regulatory (RLC) light chains. S15D-RLC phosphomimetic was reconstituted in left ventricular papillary muscle (LVPM) fibers from two mouse models of cardiomyopathy, RCM-E143K ELC and DCM-D94A RLC, along with their corresponding Tg-ELC and Tg-RLC wild type (WT) mice. The beneficial effects of S15D-RLC in rescuing cardiac function were manifested by S15D-RLC-induced destabilization of the super-relaxed (SRX) state that was observed in both models of cardiomyopathy. S15D-RLC promoted a shift from the SRX state to the disordered relaxed (DRX) state, increasing the number of heads readily available to interact with actin and produce force. Additionally, S15D-RLC reconstituted fibers demonstrated significantly higher maximal isometric force per cross-section of muscle compared with reconstitution with WT-RLC protein. The effects of the phosphomimetic S15D-RLC were compared to those observed for Omecamtiv Mecarbil (OM), a myosin activator shown to bind to the catalytic site of cardiac myosin and increase myocardial contractility. A similar SRX↔DRX equilibrium shift was observed in OM=treated fibers as in S15D-RLC-reconstituted preparations. Additionally, treatment with OM resulted in significantly higher maximal pCa 4 force per cross-section of muscle fibers in both cardiomyopathy models. Our results suggest that both treatments with S15D-RLC and OM may improve the function of myosin motors and cardiac muscle contraction in RCM-ELC and DCM-RLC mice.

N-acetyl-L-cysteine (NAC), a sulfhydryl-containing compound, is mainly used as a mucolytic and as an antidote for acetaminophen overdose. Flow injection and sequential injection systems were designed and optimized with the aim of providing precise, accurate and reliable flow methods for NAC determination in pharmaceuticals with very low sample and reagent consumption. Proposed methods are based on a redox reaction wherein NAC reduces a complex of Cu(II) and bathocuproine disulfonate (BCS) to orange [Cu(BCS)2]3– complex, which absorption was measured at λmax = 483 nm. The optimized FIA and SIA configuration yielded a linear calibration curve with correlation coefficients (R2 = 0.9999 and R2 = 0.9996) in the concentration range of 3.0 × 10–7 – 3.0 × 10–5 mol L–1 and analytical frequency of 120 h–1 for the FIA method and 4.0 × 10–7 – 4.0 × 10–5 mol L–1, at sampling rate 60 h–1 for the SIA method. The proposed flow methods were successfully applied for the determination of NAC in pharmaceutical products, as the results showed good agreement with the standard method prescribed by Pharmacopoeia. Recoveries were in the range from 98.4% to 101.9% for the FIA method and from 97.2% to 101.8% for the SIA method.

N-(diisopropylphosphanyl)benzamide, PhC(O)NHPiPr2, has been synthesized in good yield following two alternative procedures that employ benzamide as the starting material. The first one is a two-step preparation, in which N-(trimetilsilyl)benzamide is reacted with PiPr2Cl, to give the title compound in good yield, whereas the second one is a straightforward synthesis which converts benzamide into N-(diisopropylphosphanyl)benzamide by reaction with PiPr2Cl in the presence of N,N-dimethylpyridin-4-amine (DMAP) and triethylamine. NMR spectroscopy and X-ray diffraction analyses have been performed to characterize the new compound and elucidate its molecular structure in the solid state. N-(diisopropylphosphanyl)benzamide adds to the limited family of amido-substituted phosphines, RC(O)NHPR’2, which can be classified as bidentate hybrid P,O-ligands, both in their neutral and anionic forms, the latter achievable by deprotonation of the NH group.

To compare concentrations of endogenous N-acylethanolamines (NAEs) lipid mediators pal-mitoylethanolamide (PEA), oleoylethanolamide (OEA), and anandamide (AEA) in fresh, decon-taminated, cryopreserved and freeze-dried amniotic membrane (AM) allografts. Thereby deter-mining whether AM's analgesic and anti-inflammatory efficiency related to NAEs persists during storage. The concentrations of NAEs were measured using ultra-high-performance liquid chro-matography-tandem mass spectrometry. Indirect fluorescent immunohistochemistry was used to detect the PEA PPARα receptor. The concentrations of PEA, OEA, and AEA were significantly higher after decontamination. A significant decrease was found in cryopreserved AM compared to decontaminated tissue for PEA but not for OEA and AEA. However, significantly higher val-ues for all NAEs were detected in cryopreserved samples compared to fresh tissue before decon-tamination. The freeze-dried AM had similar values to decontaminated AM with no statistically significant difference. The nuclear staining of PPARα receptor was clearly visible in all specimens. The stability of NAEs in AM after cryopreservation was demonstrated under tissue bank storage conditions. However, a significant decrease, but still higher concentration of PEA compared to fresh not decontaminated tissue was found in cryopreserved, but not frieze-dried AM. Results in-dicate that NAEs persist during storage in levels sufficient for the analgesic and anti-inflammatory effects of AM allografts.

High-quality rice (Oryza sativa L.) is increasingly widely planted in China with the improvement of people's living standards and the achievement of rice breeding efforts in recent years. However, the agronomic and physiological performances of high-quality indica rice (HQIR) under different nitrogen(N) application conditions in southern China are little known. Two-year consecutive field experiments were conducted with two HQIR and two ordinary-quality indica rice (OQIR) varieties under moderate and high N application rates, with yield and yield components, biomass, N up-take, and their related traits investigated. We found that grain yields of HQIR were slightly de-creased, but grain yields of OQIR were significantly increased by 6.60%-8.88% under high N rate compared with moderate N rate in both years. Thereby, OQIR produced 8.34%-11.87% and 22.00%-22.50% higher grain yield than HQIR under moderate and high N rates, respectively. The different responses of grain yield to N application rates were mainly due to decreased grain set-ting rate in HQIR and increased spikelets m-2 in OQIR under high N rate. Furthermore, high N rate significantly reduced pre-anthesis AE and improved grain-leaf area ratio, while did not in-crease post-anthesis DM compared with moderate N rate in HQIR, which might result in carbon metabolic deterioration and imbalance of source-sink relationship and subsequently lower supply of carbohydrate to panicle. Our results suggest that a moderate N rate (165 kg N ha-1) is beneficial for HQIR varieties to balance the maximum grain yield and high quality in southern China

The present paper contains data on the density (ρ), sound velocity (u), specific heat capacity (c_p ) of the mixture of N,N-dimethylformamide + 1-butanol (DMF + BuOH) determined in the entire concentration range of solution and in the temperature range: (293.15–318.15) K. The analysis of thermodynamic functions such as isobaric molar expansion, isentropic and isothermal molar compression, isobaric and isochoric molar heat capacity, as well as their excess functions (〖 E〗_(p,m)^E,〖 K〗_(S,m)^E,〖 K〗_(T,m)^E,〖 C〗_"p,m" ^E,〖 C〗_"V,m" ^E) and also V_m^E was undertaken. The analysis of changes in the physicochemical quantities was based on consideration of the system in an aspect of intermolecular interactions with resulting changes in the mixture structure. The results available in the literature are confusing during the analysis and became the reason for our decision to thoroughly examine the system. What is more, for a system whose components are widely used, there is no information in the literature regarding the heat capacity of the tested mixture, which was also achieved and presented in this publication. The conclusions drawn from so many data allow us to approximate and understand the changes that occur in the structure of the system due to repeatability and consistency of the obtained results

This article introduces ten similarity measures that utilize cosine and cotangent functions to compare (m,n)-rung orthopair fuzzy sets, this a super class of q-rung orthopair fuzzy sets. Further, we applied our established weighted similarity measures to medical diagnosis, pattern recognition,and building material problems and also presented the comparison between established measures with the existing cosine and cotangent measures of q-rung orthopair, pythagorean and intuitionistic fuzzy sets. Lastly, we considered a numerical example that demonstrates the effective and scientific application of these similarity measures in plant leaf disease classification. Furthermore, we present graphical interpretations to demonstrate the effectiveness of our established measures.

The co-occurrence of depression and obesity has become a significant public health concern worldwide. Recent studies have shown that metabolic dysfunction, which is commonly observed in obese individuals and characterized by inflammation, insulin resistance, leptin resistance, and hypertension, is a critical risk factor for depression. This dysfunction may induce structural and functional changes in the brain, ultimately contributing to depression's development. Given that obesity and depression mutually increase each other's risk of development by 50-60%, there is a need for effective interventions that address both conditions. The comorbidity of depression with obesity and metabolic dysregulation is thought to be related to chronic low-grade inflammation, characterized by increased circulating levels of pro-inflammatory cytokines, and C-reactive protein (CRP). As pharmacotherapy fails in at least 30-40% of cases to adequately treat major depressive disorder, a nutritional approach is emerging as a promising alternative. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a promising dietary intervention that can reduce inflammatory biomarkers, particularly in patients with high levels of inflammation, including pregnant women with gestational diabetes, patients with type 2 diabetes mellitus, and overweight individuals with major depressive disorder. Further effort directed to implement these strategies in clinical practice could contribute to improved outcomes in patients with depression and comorbid obesity and/or metabolic dysregulation.

The paper considers coherent states for the representation of Weyl commutation relations over a field of $p$-adic numbers. A geometric object, a lattice in vector space over a field of p-adic numbers, corresponds to the family of coherent states. It is proved that the bases of coherent states corresponding to different lattices are mutually unbiased, and the operators defining the quantization of symplectic dynamics are Hadamard operators.

In this work, we developed a highly sensitive multiplexed immunosensor for direct simultaneous detection of both N-terminal Natriuretic Peptide (NT-proBNP) and Cortisol in human artificial saliva (AS). The developed biosensor platform based on silicon nitride was composed from four gold working microelectrodes (WEs) and an integrated counter and reference electrode. Gold WEs were biofunctionalized through carboxyl diazonium (4-APA) to immobilize both anti- NT-proBNP and anti-Cortisol antibodies for simultaneous detection. The electroaddressing of the 4-APA onto the gold WE surfaces was realized by cyclic voltammetry (CV), while the interaction between antibodies and antigens in PBS was monitored by electrochemical impedance spectroscopy (EIS). The antigen detection in human AS was realized by EIS combined with the standard addition method. The immunesensor was highly sensitive and selective toward the corresponding biomarkers in both PBS and artificial human saliva as well as in the presence of other potential interfering biomarkers such as tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10). The limit of detection (LOD) was at 0.2pg/mL for NT-proBNP within the range 0.03 to 0.9pg/mL, while the LOD for Cortisol was 0.06 ng/mL within the range 0.02 to 0.6 ng/mL for Cortisol in artificial saliva. The developed immunosensor is very promising for significant detection time reducing as it allows the simultaneous detection of various biomarkers.

The following system of equations {x_1 \cdot x_1=x_2, x_2 \cdot x_2=x_3, 2^{2^{x_1}}=x_3, x_4 \cdot x_5=x_2, x_6 \cdot x_7=x_2} has exactly one solution in ({\mathbb N}\{0,1})^7, namely (2,4,16,2,2,2,2). Hypothesis 1 states that if a system of equations S \subseteq {x_i \cdot x_j=x_k: i,j,k \in {1,...,7}} \cup {2^{2^{x_j}}=x_k: j,k \in {1,...,7}} has at most five equations and at most finitely many solutions in ({\mathbb N}\{0,1})^7, then each such solution (x_1,...,x_7) satisfies x_1,...,x_7 \leq 16. Hypothesis 1 implies that there are infinitely many composite numbers of the form 2^{2^{n}}+1. Hypotheses 2 and 3 are of similar kind. Hypothesis 2 implies that if the equation x!+1=y^2 has at most finitely many solutions in positive integers x and y, then each such solution (x,y) belongs to the set {(4,5),(5,11),(7,71)}. Hypothesis 3 implies that if the equation x(x+1)=y! has at most finitely many solutions in positive integers x and y, then each such solution (x,y) belongs to the set {(1,2),(2,3)}. We describe semi-algorithms sem_j (j=1,2,3) that never terminate. For every j \in {1,2,3}, if Hypothesis j is true, then sem_j endlessly prints consecutive positive integers starting from 1. For every j \in {1,2,3}, if Hypothesis j is false, then sem_j prints a finite number (including zero) of consecutive positive integers starting from 1.

The leaves of Ligustrum robustum have been applied as Ku-Ding-Cha, a functional tea to clear heat and remove toxins; and served as a folk medicine to deal with diabetes, obesity, and hypertension. Trans-p-hydroxycinnamic acid and its esters, which were isolated from the leaves of L. robustum, might be a new resource to prevent diabetes and its complications because of their strong -glucosidase and fatty acid synthase (FAS) inhibitory activities and antioxidant effect. However, the quantitative analytical method for trans-p-hydroxycinnamic acid and its esters in the leaves of L. robustum hasn’t been reported so far. In addition, it was difficult and troublesome to analyze no less than 34 trans-p-hydroxycinnamic acid esters by usual HPLC. Therefore, a new HPLC-UV method using hydrolyzation with sodium hydroxide for quantitation of trans-p-hydroxycinnamic acid and its esters in the leaves of L. robustum was developed in the present study. The optimal hydrolyzation conditions were as follows: 1 mL sodium hydroxide aqueous solution (1 M) was added into 1 mL the extract of L. robustum and incubated at 80 °C for 2 h , and then 1 mL hydrochloride (1 M) solution was added. HPLC analysis was performed in reverse phase mode using a C-18 column, eluting with methanol-0.1% acetic acid aqueous solution (40:60, v/v) in isocratic mode at a flow rate of 1.0 mL/min, and detecting at 310 nm. The analytical method was simple and rapid, which simplified greatly the analytical process. The method was validated in terms of linearity, limit of detection (LOD), limit of quantification (LOQ), precision, and accuracy. High linearity was demonstrated with correlation coefficient of 1.000 for trans-p-hydroxycinnamic acid. The LOD and LOQ values were 1.55 and 4.69 μg/mL, respectively. The relative standard deviations (RSD) of intra-day and inter-day variabilities for trans-p-hydroxycinnamic acid were less than 2%. The percentage recovery of trans-p-hydroxycinnamic acid was 101.2% ± 0.8%. Finally, the proposed method was applied successfully to the determination and comparison of the contents of trans-p-hydroxycinnamic acid and its esters in various extracts of the leaves of L. robustum. The 60%-70% ethanol extracts of L. robustum showed the highest contents of free trans-p-hydroxycinnamic acid (3.96-3.99 mg/g), and the 50%-80% ethanol extracts of L. robustum displayed the highest contents of trans-p-hydroxycinnamic acid esters (202.6-210.6 mg/g). The method can be applied also to the quality control of the products of L. robustum.

Graphene-based nanomaterials have emerged as promising materials for a wide range of applications.. Therefore, in the last years carbon nanoparticles have attracted great attention due to their low toxicity, high biocompatibility and easy preparation. Recently, N-doped carbon nanoparticles have been shown to have improved antibacterial activity over the undoped nanomaterial, but it is difficult to find correlations between the structure of the nanoparticle and its antibacterial activity. With this purpose, here, we analyze the effect of both, the nanoparticle size and the surface chemical composition of four N-doped carbon nanoparticles on the growth of Escherichia coli bacteria. Our results were analyzed using a Ligand-Substrate model based on the Monod´s equation, which allows us to interpret the dependence of the nanoparticle-bacteria affinity with the nanomaterial structure.

The goal of the manuscript is to design a relatively best control structure for the noise suppression of a drone’s camera gimbal action. The gimbal’s movement can be simplified as a rest-to-rest reorientation system that can achieve the boundary result of a dynamic system. Six different control architectures are proposed and evaluated based on their ability to control the trajectory of the dynamic-system position and speed, their running time, and quadratic cost. The robustness of the control architecture to uncertainties in inertia and sensor noise is also analyzed. Monte Carlo figures are used to assess the performance of the six control systems. The conditions for applying different architectures are identified through this analysis. The analysis and experimental tests reveal the most suitable control of the drone’s camera gimbal rotation.

Dubermatinib (DMB, TP-0903), a benzenesulfonamide, is an inhibitor of the tyrosine kinase AXL, which is a member of the TAM family, and can prevent GAS6-mediated activation of AXL in cancer cells. Patients with previously treated chronic lymphocytic leukemia are being studied in phase I/II clinical trials to determine its antineoplastic potential (CLL). In the current work, the reactive intermediates of DMB were studied using liquid chromatography-mass spectrometry (LC-MS). Human liver microsomes (HLMs) were exposed to dimethylbenzene in a laboratory setting, and the resulting metabolites were collected through protein precipitation. Intense reactivity toward nucleophilic macromolecules was seen in the metabolites of the piperazine and pyrimidine rings in DMB, iminium and 2,5-quinone-imine, respectively. To assess the toxicities of the possibly reactive metabolites, DMB was incubated with HLMs in the presence of 1.0 mM KCN and 1.0 mM glutathione. The DMB metabolites found by LC-MS/MS were seven in vitro phase I metabolites, three cyano adducts, and two GSH conjugates. Phase I in vitro metabolic reactions included N-demethylation, hydroxylation, and dechlorination. The in vitro metabolism of DMB and the metabolites it produces have not been studied before.

A controllable synthesis of trisubstituted imidazoles and pyrroles has been developed through rhodium(II)-catalyzed regioselective annulation of N-sulfonyl-1,2,3-trizaoles with β-enaminones. The imidazole ring was formed through 1,1-insertion of N-H bond to α-imino rhodium carbene and subsequential intramolecular 1,4-conjugate addition when α-carbon atom of amino group bearing with methyl, whereas utilizing phenyl substituent constructed pyrrole ring via intramolecular nucleophilic addition. Features such as mild conditions, good functional groups tolerance, gram-scale synthesis, and valuable transformations of the products qualified this unique protocol as an efficient tool for the synthesis of N-heterocycles.

All severe cases of SARS-CoV-2 infections are characterized by a high risk of disease progression towards ARDS, leading to bad outcome. Respiratory symptoms in COVID-19 patients often do not correspond to disease’s worsening. A dysregulated host response to the large viral load could play a key role in the disease progression. In our sample median age was 74 years (72-75) and 54% were men. Median period of hospitalization was 9 days. Firstly, we observed an asynchronous trend of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) in 764 selected among 963 patients who were consecutively recruited in two hospitals (Cannizzaro, S. Marco) in Catania, Italy. NLR values in deceased patients showed an increase from baseline over time. By contrast, CRP tended to fall from baseline to median day of hospitalization in all four subgroups, but steeply increased at the end of hospitalization only in ICU-admitted patients. Then we evaluated the relationships between NLR and CRP as continuous variables with PaO2/FiO2 ratio (P/F). Finally, we made mediation and moderation analyses to determine the link between inflammation (CRP), immune system (neutrophils and lymphocytes) and respiratory failure (P/F). CRP, neutrophils and P/F are linked in the same pathogenetic chain leading to respiratory failure.

In this article, the multitouch option, also called the n  touch option (or the “baseball” option when n  3 ) is analyzed and valued in closed form. This is a kind of barrier option that sets a gradual knockout / knock-in mechanism based on the number of times the underlying asset has crossed a predefined barrier in various time intervals before expiry. The higher the number of predefined time intervals during which the barrier has been touched, the lower the value of a knock-out contract at expiry, and conversely for a knock-in one. Multitouch options can be viewed as an extension of step barrier options, preserving the ability of the latter to adjust the exposure to risk over time, while eliminating the notorious danger of “sudden death” that holders of step barrier options are faced with. Unlike occupation time derivatives, the payoff at expiry does not depend on the amount of time spent outside the authorized range, but on the number of passages beyond the authorized range.