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.

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.

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.

Introduction: The objectives of this study were to (1) investigate the association between human blood type and COVID-19 infection in both inpatient and longitudinal populations at our institution in South Florida and (2) identify the association between blood type and severity of COVID-19 infection via presence of cellular biomarkers of severe infection in hospitalized individuals. Methods: This study consists of (1) a single-center retrospective analysis of 669 of 2,741 COVID-19 positive screened patients seen from January 1, 2020 until March 31, 2021 at the University of Miami Emergency Department (ED) who tested positive for COVID-19 infection and had a documented ABO blood type and (2) a longitudinal SARS-CoV-2 immunity study (“CITY”) at the University of Miami Miller School of Medicine consisting of 185 survey participants. COVID-19 outcome rates and 95% confidence intervals were calculated for each ABO blood type and Rh group using Chi-squared tests for categorical and ANOVA for continuous variables in the inpatient cohort and Chi-squared tests for the longitudinal cohort, all executed in R studio. Results: Our inpatient cohort had a mean age of 53.6 (± 17.9) years with 48% males and 52% females. When compared to patients with other blood types, those with O- demonstrated less risk of developing COVID-19 pneumonia (26.7% for O- vs. 69.2% for type A-, 56.5% for A+, 71.4% for AB+, 53.7% for B+, 51.5% for O+, p-value= 0.003 via Chi-squared test) and decreased mortality due to COVID-19 infection (17.0% mortality for O vs. 26.3% for A, 29.2% for B, p-value= 0.012 via Chi-squared test). Blood type O- demonstrated less elevated levels of LDH than did other blood types (p-value= 0.001, ANOVA) and a higher frequency of clinically accepted baseline levels of troponin (0.04 ng/mL) (p-value= 0.026, ANOVA) (Figure 1). Most of the longitudinal cohort was ABO blood grouping type O (47% (87/185)), with 33.5% type A, 14.1% B, and 5.4% AB. Most individuals were Rh positive (85.9%). There was no significant association found between COVID status (infection vs. non-infection) and ABO (Chi-squared test (3, N = 185) = 1.8, p = 0.6) or Rh (Chi-squared test (1, N = 185) = 0.16, p = 0.7) blood typing. Nearly all participants had been vaccinated (95.1% (176/185)), with a majority reporting primary vaccination with Pfizer (57.8% (107/185)), followed by Moderna (33% (61/185)), and Johnson & Johnson (4.3% (8/185)). 8 participants (4.3%) were unvaccinated. Conclusions: In an inpatient setting, blood type O sustained less risk of COVID-19 mortality and O- demonstrated less risk of developing COVID-19 pneumonia. In a longitudinal setting, there was no association found between blood type and COVID-19 severity. As the novelty of COVID-19 infection declines with time, further studies on risk-stratification by blood type are encouraged.

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.

The rapid, sensitive, and selective detection of pathogenic bacteria is of utmost importance in ensuring food safety and preventing the spread of infectious diseases. Here, we present a novel, reusable, and cost-effective impedimetric sensor based on a dual bacteria-imprinted polymer (DBIP) for the specific detection of Escherichia coli O157:H7 and Staphylococcus aureus. The DBIP sensor stands out with its remarkably short fabrication time of just 20 minutes, achieved through the efficient electro-polymerization of o-phenylenediamine monomer in the presence of dual bacterial templates, followed by in-situ template removal. The key structural feature of the DBIP sensor lies in the cavity-free imprinting sites, indicative of a thin layer of bacterial surface imprinting. This facilitates rapid rebinding of the target bacteria within a mere 15 minutes, while the sensing interface regenerates in just 10 minutes, enhancing the sensor's overall efficiency. A notable advantage of the DBIP sensor is its exceptional selectivity, capable of distinguishing the target bacteria from closely related bacterial strains, including different serotypes. Moreover, the sensor exhibits high sensitivity, showcasing a low detection limit of approximately 9 CFU mL-1. The sensor's reusability further enhances its cost-effectiveness, reducing the need for frequent sensor replacements. The practicality of the DBIP sensor was demonstrated in the analysis of real apple juice samples, yielding good recoveries. The integration of quick fabrication, high selectivity, rapid response, sensitivity, and reusability makes the DBIP sensor a promising solution for monitoring pathogenic bacteria, playing a crucial role in ensuring food safety and safeguarding public health.

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.

Background: One of the main diseases of worldwide concern is non–insulin dependent Diabetes mellitus. 90-95% of patients with diabetes suffers from Type II diabetes, a metabolic diabetes whose prevalence is increasing in the world.Given the current prevalence of diabetes type II in society, research of natural compounds able to regulate glycaemia and insulin–resistance is nowadays covering importance, as alternative or co–adjuvant treatment to existing hypoglycaemic medicines. In pre–clinical steps of research, C. elegans is considered a promising in vivo model for the study of the molecular mechanism of glucose as part of anti–diabetic bioactivity.Most of the studies of insulin resistance with this in vivo model are carried out by using mutant strains such as daf-2 and the effects of the compounds are attributed a posteriori, after a physiological response of the worms rather than directly measuring preservation of activity inside the worm. Methods: The in vitro α-glucosidase inhibition of two oral formulations with Origanum vulgare extract before and after a simulated process of gastrointestinal digestion was evaluated. After confirming the in vitro activity, the α-glucosidase inhibition was tested in vivo through the new method proposed. Results: The crude extract showed an IC50 value similar to acarbose (positive control), before and after the gastrointestinal digestion. The encapsulated extract (111.86±1.25 µg/mL) did not present statistical differences with the positive control (110.10±1.15 µg/mL) after digestion. However, the powder formulation showed the highest hypoglycaemic activity (59.55±0.85 µg/mL).In vivo, the IC50 values showed similar profile than in vitro. Conclusion: A new simple and reliable method has been developed to determine pharmacological activities inside in vivo model C. elegans.The method has been evaluated with a hydroalcoholic extract of O. vulgare. The method is accurate and valid for the quantification of the inhibition of in vivo, allowing the direct attribution of this in vivo hypoglycaemic activity to the treatment. In addition, it opens the door to further research into in vitro pharmacological activities that require an in vivo counterpart.

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.

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.

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.

A series of alpha,omega-bis(o-methoxyphenyl)arenes were prepared through Suzuki-Miyaura coupling reactions of dibromoarenes with o-methoxyphenyl boronic acid. P2O5-CH3SO3H-mediated direct polycondensation of alpha,omega-bis(o-methoxyphenyl)arenes with trans-1,4-cyclohexanedicarboxylic acid proceeded regioselectively to afford 1,4-cyclohexanediyl-containing aromatic polyketones. The resulting aromatic polyketones have high Tg and excellent solubility in typical organic solvents. In addition, the polyketone films fabricated by solution casting method are more colorless and transparent than those without cyclohexanediyl units.

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.

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.

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.

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.

Classifying spinal tumors can be challenging due to nonspecific clinical and radiological qualities, and a precise biopsy is crucial for an accurate diagnosis and treatment planning. This study aimed to enhance the accuracy and efficiency of spinal biopsies integrating Cone Beam Computed Tomography (CBCT) and magnetic resonance imaging (MRI) modalities using an O-arm CT navigation system. Eighteen patients with diverse spinal lesions underwent 18 biopsies following the Stealth Station navigation system Spine 8 protocol. Preoperative MRI scans were merged with intraoperative CT navigation systems for continuous monitoring during the biopsy process. The combined imaging technique accurately identified the diseased lesion type in all biopsies, demonstrating 100% sensitivity and specificity. In conclusion, combining MRI and CT imaging modalities significantly improved spinal biopsy accuracy and efficiency, differentiating between pathological entities. However, large-scale studies are desired to validate these findings and investigate potential benefits in different clinical scenarios. Although this method requires general anesthesia, its potential profits in avoiding misdiagnosed lesions and decreasing the need for further invasive procedures make it a promising approach for improving spinal biopsy accuracy and efficiency.

Tea (Camellia sinensis) is one of the most popular beverages worldwide. Many types of tea prod-ucts continuously emerge in an endless stream; so, the classification or verification of tea be-comes more difficult. Aroma is a vital indicator of tea quality. The present study deals with the identification of aroma compounds in 18 different kinds of tea belonging to three typical tea va-rieties, including green tea, oolong tea, and black tea, using GC-IMS and GC×GC-O-MS. More-over, the clustering of all 18 tea samples and the in-depth correlation analysis between sensory evaluation and instrumental data were performed using the PCA and OPLS-DA. The results re-vealed that in all 18 kinds of tea, a total of 85 aroma compounds were detected by GC-IMS, whereas 318 were detected by GC×GC-O-MS. The PCA result revealed that green tea, oolong tea, and black tea could be clearly separated based on their peak areas. The OPLS-DA result showed that a total of 49 aroma compounds with VIP value > 1.0 could be considered as the potential in-dicators to quickly classify or verify tea types. This study not only compared the aroma differ-ences across different types of teas, but also provided ideas for the rapid monitoring of tea qual-ity and variety.

The objective of this study is to design and synthesize substituted η6-chromium tricarbonyl metal complexes carrying o-carborane units as potential boron neutron capture therapy (BNCT) agents. In this study, 1,2-Diphenyl-o-carborane units were used as starting materials to generate biologically active species. We investigated how the structural changes of 1,2-diphenyl-o-carborane substituted with chromium(0) tricarbonyl affect the biological properties; [(CO)3Cr]Ph2C2 (2) and [(CO)3Cr]2Ph2C2 (3) species were produced in moderate yields. The molecular structures of compounds 1–3 were identified and established by infrared (IR), 1H, 11B, and 13C nuclear magnetic resonance (NMR), and X-ray crystallography analyses. Crystal structures of o-carboranyl chromium complexes 1 [a = 10.859(1) Å, b = 24.953(3) Å, c = 13.938(2) Å, β = 111.854(2)º], 2 [a = 10.621(3) Å, b = 17.056(5) Å, c = 12.174(4) Å, β = 106.622(5)º], and 3 [a = 17.540(2) Å, b = 18.060(2) Å, c = 19.484(4) Å, α = 105.746(2)º, β = 110.226(2)º, γ = 91.256(2)º] were obtained. In vitro study using B16 and CT26 cancer cells containing the triphenyl-o-carboranyl chromium (0) complexes Ph3C2BCr2 and Ph3C2BCr3, which we have previously reported, the compounds 2 and 3 accumulated at higher levels than compounds Ph3C2BCr2 and Ph3C2BCr3. However, the phenylated o-carboranyl chromium(0) complexes have been found to be more cytotoxic than p-boronophenylalanine (BPA).

Advanced MRI methods and PET using radiolabeled amino acids provide valuable information in addition to conventional MR imaging for brain tumor diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumor progression from treatment-related changes, and the early assessment of response to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing and has been addressed in numerous studies. Currently, most radiology and nuclear medicine departments perform these examinations independently of each other leading to multiple examinations for the patient. The advent of hybrid PET/MRI allowed a convergence of the methods but to date simultaneous imaging has reached little relevance in clinical neuro-oncology. This is partly due to the limited availability of hybrid PET/MRI scanners, but is also due to the fact that PET is a second-line examination in brain tumors. PET is only required in equivocal situations, and spatial co-registration of PET examinations of the brain to previous MRI is possible without disadvantage. A key factor for the benefit of PET/MRI in neuro-oncology is a multimodal approach that provides decisive improvements in the diagnostics of brain tumors compared with a single modality. This systematic review focuses on studies that were able to demonstrate the additive value of amino acid PET and ‘advanced’ MRI in the diagnosis of brain tumors. Available studies suggest that the combination of amino acid PET and advanced MRI improves grading and the histomolecular characterization of newly diagnosed tumors. However, data concerning the delineation of tumor extent and biopsy guidance are of limited value. A clear additive diagnostic value of amino acid PET and advanced MRI can be achieved regarding the differentiation of tumor recurrence from treatment-related changes. Here, PET-guided evaluation of advanced MR methods seems to be helpful. In summary, there is growing evidence that a multimodal approach can achieve decisive improvements in the diagnostics of brain tumors, for which hybrid PET/MRI offers optimal conditions.

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.

In the present paper we introduce three new classes of bi-univalent functions connected with Gregory coefficients. For functions in each of these three bi-univalent function classes we have derived the estimates of the Taylor--Maclaurin coefficients $\left|a_{2}\right|$ and $\left|a_{3}\right|$ and Fekete-Szeg\H{o} functional problems for functions belonging to these new subclasses. We defined three subclasses of the class of the bi-univalent functions $\Sigma$, namely $\mathfrak{HG}_{\Sigma}$, $\mathfrak{GM}_{\Sigma}(\mu)$ and $\mathfrak{G}_{\Sigma}(\lambda)$ by using the subordinations with the function whose coefficients are Gregory's numbers. First, we proved that these classes are not empty, i.e. contains other functions than the identity one. Using the well-known Carath\'eodory Lemma for the functions with real positive parts in the open unit disk, together with an estimation due to P. Zaprawa (see https://doi.org/10.1155/2014/357480) and another one of Libera and Zlotkiewicz, we gave upper bounds for the above mentioned initial coefficients and for the Fekete-Szeg\H{o} functionals. The main results are followed by some particular cases, and the novelty of the definitions and the proofs could involve further studies for such type of similarly defined subclasses.

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.

Protein O-GlcNAcylation has been associated with neurodegenerative diseases such as Alzheimer´s disease (AD). O-GlcNAcylation of Amyloid Precursor Protein (APP) regulates both the trafficking and the processing of the APP through the amyloidogenic pathway, resulting in the release and aggregation of the Aβ1-42 peptide. Microglia clear Aβ aggregates and dead cells to maintain brain homeostasis. Here, using LC-MS/MS we reveal that the Aβ1-42 peptide modifies the microglia O-GlcNAcome. We have identified 55 proteins, focusing our research on Galectin-1 protein, since it is a very versatile protein from a functional point of view. Combining biochemical with genetic approaches we demonstrate that Aβ1-42 peptide specifically targets Galectin-1S8 O-GlcNAcylation via OGT. In addition, this Gal-1-O-GlcNAcylated form, in turn, controls human microglia migration. Given the importance of microglia migration in the progression of AD, this study reports the relationship between Aβ1-42 peptide and Serine 8- O-GlcNAcylation of Galectin to drive microglial migration

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.

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.

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.

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.

In this paper, new N-way Wilkinson power dividers (WPDs) are represented by using slow-wave structures such as narrow slits loaded and meandered transmission lines. The slit loaded and meandered lines are used to represent the quarter wavelength transmission lines of a conventional WPD for size reduction. Based on the proposed approaches, 2-, 4- and 8-way power dividers are designed, simulated and fabricated. The fabricated -, 4- and 8-way circuits have been measured at the center frequencies of 2.03, 1.77, and 1.73 GHz in an excellent agreement with the predicted ones. The meandered transmission lines are also used to design new types of WPDs having novel input/output port arrangements. For this purpose, two 3-way WPDs are located at both sides of the same board so as to have different power splitting ratios at different inputs and outputs to provide alternative solutions for antenna arrays. Furthermore, a 5-way dual layer WPD is introduced by locating the meandered transmission lines to two layers. The proposed 3- and 5-way WPDs allow halving the input power at the next output port in the order of P/2, P/4, P/8, P/16, and P/16. All of the designed power halving WPDs have been simulated, fabricated and successfully tested.

Organic light-emitting diodes (OLEDs) are energy-efficient; however, the coordinating ligand can affect their stability. Sky-blue phosphorescent Pt(II) complexes with a C^N chelate, fluorinated-dbi (dbi = [1-(2,4-diisopropyldibenzo[b,d]furan-3-yl)-2-phenyl-1H-imidazole]), and acetylactonate (acac)(1)/picolinate (pic)(2) ancillary ligands were synthesized. The molecular structures were characterized using various spectroscopic methods. The Pt(II) coordination sphere in 2 exhibited a distorted square-planar geometry, with several intra- and inter-molecular interactions involving Cπ⋯H/Cπ⋯Cπ stacking. Complex 1 emitted bright sky-blue light (λmax = 485 nm) with a moderate photoluminescent quantum efficiency of 0.37 and short decay time (6.1 µs) compared to those of 2. Time-dependent density functional theory calculations suggested that the electronic transition of 1 arose from ligand(C^N)-centered π–π* transitions combined with metal-to-ligand charge transfer transitions (MLCT), whereas that of 2 arose from MLCT and ligand(C^N)-to-ligand(pic) charge transfer (LLCT), with minimal contribution from the C^N chelate to the lowest unoccupied molecular orbital. Multi-layered phosphorescent OLEDs using 1 as a dopant and a mixed host, 3,3-di(9H-carbazol-9-yl)-1,1-biphenyl:3-di(9H-carbazol-9-yl)-1,1-biphenyl (mCBP)/9-(3’-carbazol-9-yl-5-cyano-biphenyl-3-yl)-9H-carbazole-3-carbonitrile (CNmCBPCN) were successfully fabricated. At a 10% doping of 1, a current efficiency of 13.6 cd A−1 and external quantum efficiency of 8.4 % at 100 cd m−2 were achieved. These results show that the ancillary ligand in phosphorescent Pt(II) complexes must be considered.

To study the influence of electrothermal effect of ESD protection device on the reliability of inte-grated circuit,a theoretical model of ESD protection device thermal resistance is constructed in the paper based on the Conservation of Energy Principle. By analyzing the temperature relativity between electricity parameter and thermology parameter of ESD protection device characterized by self-heating thermal resistance, the quantitative relationship expression of physical parameter and geometric parameter is obtained, which can be used to improve ESD protection device elec-tro-thermal effect. The simulation testing and the real tape-out testing of ESD protection device self-heating thermal resistance based on ggNMOS are shown and compared. It is concluded that self-heating thermal resistance is an effective index for the protection device electrothermal char-acterization. Based on the established model, the self-heating thermal resistance could be decreased to improve the homogeneity of the heat transference. The uneven distribution of device temperature can be reduced, and the overall reliability of chips can be improved.

This study employed a TSMC 0.18-µm 50 V process to establish a high-voltage n-LDMOS structure. In the reference device, the number of floating-poly (poly-2) turns was 7, and the width and spacing of each turn was 1 µm. Although increasing the number of turns reduces the peak field, directly reducing or increasing the number of poly-2 turns is a common practice. The present experiment was realized in three steps, namely fixing the number of occupied area adjustment turns, adjusting the width of each turn, and adjusting the distance between turns. The first step was fixing the number of occupied area adjustment turns. The number of turns was increased from 7 to 9, and the number of turns was reduced to 5 and 3 in the reference group. A reduction in the number of turns led to a greater decrease in the peak field and increase in the breakdown voltage despite the area remaining unchanged. A comparison of the use of three turns with that of seven turns revealed that the maximum electric field decreased by 42%, from 4.17e+3 to 2.46e+3 V/cm, and that the breakdown voltage (VBK) increased from 30.2 to 35.84 V. The second step was adjusting the width of each turn from 1 to 1.4, 1.2, 0.8, and 0.6 µm in the reference group. This increase in width reduced the maximum electric field and led to a greater increase in VBK. When the width was increased to 1.4 µm, the maximum electric field decreased by 29% from 1.95e+3 to 1.4e+3 V/cm, and the VBK increased by 183% from 30.2 to 85.6 V. The third step was adjusting the spacing of each turn from 1 to 1.4, 1.2, 0.8, and 0.6 µm in the reference group. The results revealed that a reduction in the spacing led to a greater reduction in the maximum electric field and an in-crease in the VBK. When the pitch was reduced to 0.6 µm, the maximum electric field decreased by 33%, from 1.95e+3 to 1.32e+3 V/cm, and the VBK increased by 345%, from 30.2 to 134.4 V.

The military taxonomy of class indices for chemical and biological warfare agents considers halogenated tear agents (CS) to be incapacitating causing local pain and discomfort with associated reflexe. The removal yield of the organic substances present in the water depends on the environmental conditions, on the chemical composition of the water and on the chemical substance dissolved in the water, which constitutes the substrate of the metabolic activities of the microorganisms that use these substances in the biochemical reactions of the cellular enzyme complexes. The two -CN groups in the malonic nitrile molecule are strongly electron-attracting and activate the CH2 group to which they are linked, and because of this, malononitrile has the role of a methylene component in condensation reactions with aldehydes or ketones. The results obtained after analyzing the degree of hydrolysis in the samples that contained the biological suspension indicated that no CBM metabolites were detected in any biological sample, regardless of the test concentration, analyzed 24 h after incubation. In the parallel samples, the aqueous solutions of CBM without biological treatment had metabolites in the samples., at 30 minutes the degree of hydrolysis is 0.21%, at 60 minutes, the degree of hydrolysis is 5.42%, after 90 minutes, the degree of hydrolysis is 6.19%, and after 24 hours. the degree of hydrolysis is 23.41%. Chemical substances in contact with microorganisms are used by them in the biochemical processes in which they are involved, the retention time and biodegradation capacity have led to an increased effect of the metabolism of toxic substances, in metabolic reactions, organic substances are the source of carbon and energy for biochemical processes. The tests performed indicate that the suspension of Chlorella sp. consumed the entire amount of CBM and metabolites from the analyzed samples The tests prove that the biological material can be used for the decontamination of the affected areas.

A new spirurid nematode Protospirura canariensis n. sp., parasite of the black rat Rattus rattus (Rodentia: Muridae) in El Hierro Island (Canary Archipelago, Spain) is described by means of light (LM) and scanning electron microscopy (SEM). The most discriminant characteristics between the new species and the existing species in the genus Protospirura are: (a) the number of tooth-like prominences in the submedian and lateral lobes of pseudolabia, both in males and females (2 and 4, respectively), (b) the size of right and left spicules in males (643–715 µm and 309–412 µm, respectively), and (c) the number and arrangement of cloacal papillae in males. The new species has a total of 17 cloacal papillae (four large and pedunculated pairs of precloacal papillae, an unpaired precloacal papilla and four pairs of postcloacal papillae). The arrangement of postcloacal papillae are as follows: the first pair are large, pedunculated and placed near the posterior edge of cloaca; the three remaining postcloacal pairs are grouped and located near the posterior tip. In the latter group, papillae in the first pair are large and pedunculated. Parasitized host and geographical distribution are also useful criteria to distinguish P. canariensis n. sp. from the remaining species of the genus Protospirura. In addition, the cytochrome c oxidase subunit 1 (cox1) sequence of the new species is provided and compared with available data of related species.

The chelating aluminum complex [2-(Me2NCH2)C2B10H10]AlX2 (X = Br 3, CH3 4) was synthesized using 2-dimethylaminomethyl-o-carboranyl lithium (2) with aluminum tribromide or dimethylaluminum bromide, resulting in a modest yield. Compound 4 was obtained by reacting compound 3 with CH3Li in toluene. All compounds were characterized by infrared (IR) spectroscopy, 1H, 11B, 13C nuclear magnetic resonance (NMR) spectroscopy, and X-ray crystallography. X-ray structural studies of CabNAlBr2 (3) and CabNAlMe2 (4) indicated that the Al atom was located at the center of a distorted tetrahedron. Crystal structures of the CabNAlBr2 (3) [a = 8.9360(3) Å, b = 12.0358(9) Å, c = 14.7730(4) Å, α = β = γ = 90°] and the CabNAlMe2 (4) [a = 8.9551(3) Å, b = 11.9126(9) Å, c = 14.7711(4) Å, α = β = γ = 90°] were obtained. The reactivity of aluminum complexes 3 and 4 with Lewis bases, such as H2O, pyridine, alkylamines, and arylamines, confirmed their rapid decomposition.

Seafood products are the main dietary source of n-3 polyunsaturated fatty acids (n-3 PUFA), which are essential for human health. However, due to the widespread use of processed fish products, the presence of these n-3 PUFAs may be subject to changes related to different processing methods. The aim of this study was to determine the fatty acid composition, with a focus on n-3 polyunsaturated fatty acids (n-3 PUFAs), in different processed fish and shellfish food of EU and non-EU origin purchased in supermarkets and ethnic food shops in Messina (Italy), using gas chromatography with flame-ionization detector (GC-FID). From the fatty acid profile, the atherogenic index (AI), thrombogenicity index (TI) and flesh-lipid quality index (FLQ) were determined: 0.13-1.04 (AI), 0.31-9.84 (TI) and 0.41-29.90 (FLQ). The percentages of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids had the following ranges: 13.55-50.48%, 18.91-65.58%, 13.84-52.73%, respectively. All samples showed a good presence of PUFAs and, in particular, eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) were the main n-3 polyunsaturated fatty acids (n-3 PUFA).

Wobbling motion as an exotic collective mode in nuclei without axial symmetry, was intensively discussed during the last few years. The observation of the newly proposed transverse wobbling, first reported in $^{135}$Pr and soon after in nuclei from other mass regions, was considered as a significant discovery in low-spin nuclear structure. However, both the reported experimental results and the proposed theoretical models were lively questioned in a series of works devoted to the investigation of the low-spin wobbling mode in the same nucleus. The electromagnetic properties of the $\Delta I=1$ transitions connecting the one- to zero-phonon and the two- to one-phonon wobbling bands in $^{135}$Pr were recently remeasured, demonstrating their predominant $M1$ magnetic character which is in contradiction with the wobbling motion interpretation. These new experimental observables being well reproduced by both quasiparticle-plus-triaxial-rotor model and interacting boson-fermion model calculations, are against the previously proposed wobbling characteristics of the low-spin bands in $^{135}$Pr. On the other hand, we obtained conclusive experimental evidence for the theoretically suggested transverse wobbling bands at medium spin in $^{136}$Nd. The comparison of the experimental data with calculations utilizing the triaxial projected shell model and a new developed particle-rotor model with frozen orthogonal geometry of the active nucleons, supports the description in terms of transverse wobbling of medium-spin bands in triaxial even-even nuclei.

Soil nitrogen (N) is a common limiting factor where soil N cycling is a key component of agro-ecosystems. Soil N transformation processes are largely mediated by microbes and understanding bacteria involvement in soil N cycling in agricultural systems has both agronomic and environmental importance. This 2-yr field scale study examined the abundances and spatial distributions of total bacterial community (16s RNA), bacterial involved in nitrification (amoA), and de-nitrification (narG, nirK, and nosZ) and soil physicochemical properties of winter wheat (Triticum aestivum L.) – soybean (Glycene max L.) double cropping with 2-3 weeks of spring grazing (WGS) and without grazing (WS) and of tall fescue (Festuca arundinacea (L.) Schreb.) pasture (TF) managed to near natural conditions with similar grazing. The TF had a significantly higher abundance of 16S rRNA, amoA, narG, nirK, and nosZ genes than the WS and WGS, which had similar levels between themselves. Soil organic matter (OM) and soil pH had a stronger effect on the N-cycling bacteria gene abundance. All bacterial gene concentrations and soil pH showed non-random distribution patterns with 141-186 m range autocorrelation. These results indicate that biological N transformation processes are more important in natural agricultural systems and the abundance of N-cycling bacteria can be manipulated by field scale management strategies.

Differences in the physical and chemical properties of reclaimed water (RW) and natural surface water (SW) lead to the differences in terms of nitrogen and phosphorus release when pipeline sediments enter these water bodies. The nitrogen and phosphorus release kinetics from pipe sediments with different particle sizes have been investigated. The results demonstrated that both SW and RW had a pH buffering effect after sediment addition, and the final pH (approximately 8.1) of RW was lower. The release of total phosphorus (TP) and ammonia nitrogen ( NH₄⁺-N) fitted the first-order kinetic model where the release of TP reached equilibrium; TP release was inhibited in both SW and RW, where RW exhibited the lowest (by a factor of 1.23~2.44) release (0.002 mg/g). The release of NH4+-N was promoted in both SW and RW; the maximum release in RW was 0.0188 mg/g. The amounts of NH₄⁺-N released in SW and RW were 1.02-1.40 and 1.30-1.80 times that of the control group (CG), respectively. The percentage of TP and NH₄⁺-N release in the three groups was highest in 75-154 μm pipe sediment, reaching 34.53% and 43.51% in SW and RW, respectively. These results can assist in the development of water quality evolution models for specific urban scenarios, and provide important guidance for the precise regulation of recharge water quality during and after rainfall.

Ketamine is a dissociative anesthetic and antidepressant with several biological targets. Among the many targets, ketamine, notably, has an antagonistic effect on molecular N-methyl-D-aspartate (NMDA) receptors and has been identified as a non-competitive inhibitor of these receptors. Although ketamine has a wide range of therapeutic uses in the clinical setting, it is often used recreationally due to its psychoactive and analgesic effects. Regardless of the indication, prenatal exposure to ketamine has been widely investigated. The misuse of this drug, particularly in pregnant women, has been a point of concern. The neurotoxic potential of ketamine positions it as a danger to a developing fetus. Furthermore, the ability of ketamine to cross the blood-placental barrier poses a threat to the health and maturation processes of the neonate. This paper reviewed published work that explores the mechanisms through which prenatal ketamine exposure can cause altered neurodevelopment, neurobehavior, and the physiological consequences that follow. By exploring investigations using multiple different subjects such as: rodents, non-human primates, and human subjects, this paper develops a full picture of the existing data to generate a strong foundation for improved and informed public health policies.

The primary cilium plays critical roles in homeostasis and development of neurons. Recent studies demonstrate that cilia length is regulated by the metabolic state of cells, as dictated by processes such as glucose flux and O-GlcNAcylation (OGN). The study of cilia length regulation during neuron development, however, has been an area left largely unexplored. This project aims to elucidate the roles of O-GlcNAc in neuronal development through its regulation of the primary cilium. Here, we present findings suggesting that OGN levels negatively regulate cilia length on differentiated cortical neurons derived from human-induced pluripotent stem cells. In neurons, cilia length increased significantly during neurons maturation (after day 35), while OGN levels began to drop. Long-term perturbation of OGN via drugs, which inhibit or promote its cycling, during neuron development also have varying effects. Diminishing OGN levels increases cilia length until day 25, when neural stem cells expand and undergo early neurogenesis, before causing cell cycle exit defects and multinucleation. Elevating OGN levels induces greater primary cilia assembly but ultimately results in the development of premature neurons, which have higher insulin sensitivity. These results indicate that OGN levels and primary cilia length are jointly critical in proper neuron development and function. Understanding the interplays between these two nutrient sensors, O-GlcNAc and the primary cilium, during neuron development is important in paving connections between dysfunctional nutrient-sensing and early neurological disorders.

This research is focused on two key areas. The first is mapping the 2022 flood in the Red River of the North near Grafton, North Dakota, US, and the second is evaluating the scour potential of the Grafton Bridge. Local scour of bridge piers can cause hydraulic structures such as bridge piers and abutments to fail during floods, making it a crucial area of investigation. To collect bathymetry and discharge data during low and high flow conditions, including a flood event with a 16.5-year return period in 2022, an Autonomous Surface Vehicle (ASV) incorporated with LiDAR DEM (Digital Elevation Model) data obtained from the US Geological Survey (USGS) National Map was used. Flood mapping and evaluation of local scour around the bridge pier were conducted using the HEC-RAS 6.0.0 software, which utilizes the Colorado State University method as a default equation. This research demonstrates the potential of ASVs in collecting critical data and LiDAR DEM data is an efficient method for flood mapping and determining scour potential, as it integrates bathymetry, flow velocity, and flood prediction.

The excessive use of synthetic insecticides in modern agriculture has led to the contamination of the environment and the development of insect resistance. In this study, we evaluated the potential of tangerine (Citrus reticulata L.) peel essential oil (EO) as a natural insecticide against greenhouse whitefly (Trialeurodes vaporariorum W. (Homoptera: Aleyrodidae)), a common pest in greenhouse production. Petroleum ether (PET) and n-hexane (HEX) were used as solvents to extract essential oil (EO) from tangerine peels. The yield of EO was 1.59 % and 2.00 % (m/m) for PET and HEX, respectively. The insecticidal activity of EO was evaluated by measuring the mortality rate (MR) of greenhouse whiteflies at different time intervals. The results showed that PET and HEX extracts of tangerine EO effectively controlled the greenhouse whitefly. With both solvents, it was observed that with doses of 12.5% (v/v), similar results were achieved as with the positive control (corresponding to the commercial insecticide imidacloprid). Additionally, the FTIR analysis found that the EO contained d-limonene, which may be the source of its insecticidal properties. Therefore, tangerine peel essential oil is an excellent natural insecticide candidate for controlling greenhouse whiteflies effectively and sustainably.

Antisense oligonucleotide (ASO)-mediated exon skipping has become a valuable tool for investigating gene function and developing gene therapy. Machine learning-based computational methods such as eSkip-Finder have been developed to predict the efficacy of ASOs via exon skipping. However, these methods are computationally demanding, and the accuracy of predictions remains suboptimal. In this study, we propose a new approach to reduce computational burden and improve prediction performance by using feature selection within machine learning algorithms and ensemble learning techniques. We evaluated our approach using a dataset of experimentally validated exon skipping events, dividing it into training and testing sets. Our results demonstrate that using a 3-way voting approach with random forest, gradient boosting, and XGBoost can significantly reduce computation time to under ten seconds while improving prediction performance, as measured by R2 for both 2’-O-methyl nucleotides (2OMe) and phosphorodiamidate morpholino oligomers (PMOs). Additionally, the feature importance ranking derived from our approach is in good agreement with previously published results. Our findings suggest that our approach has the potential to enhance the accuracy and efficiency of predicting ASO efficacy via exon skipping. It could also facilitate the development of novel therapeutic strategies. This study could contribute to the ongoing efforts to improve ASO design and optimize gene therapy approaches.

The development of antimicrobial resistance to conventional antibiotics is a major global health challenge. Infections caused by multidrug-resistant gram-negative bacteria have been named one of the most urgent global health threats. Considerable efforts are devoted to developing new antibiotic drugs and investigating the mechanism of antibiotic resistance. Recently, Anti-Microbial Peptides (AMPs) have emerged as a new platform for the target and design of novel drug resistant anti-microbial agents promising a new therapeutic strategy. AMPs are rapid, potent, possess an unusually broad spectrum of activity, and have shown efficacy as topical agents. Unlike traditional therapeutics that interfere with essential bacterial enzymes, AMPs interact with microbial membranes through electrostatic interactions and physically damage cell integrity. However, naturally occurring AMPs have limited selectivity and modest efficacy. Therefore, recent efforts have focused on the development of synthetic AMP analogs as suitable drug targets. This work explores the development of novel antimicrobial agents which mimic the structure of graft-copolymers and mirror the mode of action of an AMP. Chitosan-graft-polypeptide side chains are synthesized by the ring-opening polymerization of N-carboxyanhydrides of L-lysine and L-leucine initiated from the functional groups of chitosan. The derivatives with random- and block-copolymer side chains are explored as drug targets. These graft copolymer systems exhibit activity against clinically significant pathogens and disrupt biofilm formation. This work highlights the potential of chitosan-graft-polypeptide structures in biomedical applications.

Antisense oligonucleotide (ASO)-mediated exon skipping has emerged as a powerful tool for examining the function of genes and exons in basic research, as well as gene therapy. Computational methods, such as eSkip-Finder, have been developed to predict the efficacy of ASOs via exon skipping using machine learning. However, these methods can be computationally demanding and the prediction accuracy of the tool is not yet optimal. In this study, we propose an approach to reduce computational burden and improve prediction performance by utilizing feature selection within machine learning algorithms and employing ensemble learning techniques. The method was evaluated using a dataset of genes with experimentally validated exon skipping events. The dataset was divided into training and testing sets to assess the accuracy of the algorithm. Our results demonstrate that using a 3-way voting approach with random forest, gradient boosting, and XGBoost can significantly reduce computation time to under ten seconds while improving prediction performance, as measured by R2 for both 2’-O-methyl nucleotides (2OMe) and phosphorodiamidate morpholino oligomers (PMOs). Additionally, the feature importance ranking derived from our approach is in good agreement with previously published results. These findings suggest that this approach has the potential to enhance the efficiency and accuracy of predicting ASO efficacy via exon skipping, facilitating the development of novel therapeutic strategies.

It was the aim of this study to compare the ratio of salbutamol and its major metabolite salbutamol-4’-O-sulfate as well as the quantity excreted renally after oral and inhalative administration. Additionally, the excretion pattern after application of racemic salbutamol opposed to the pure enantiomer levosalbutamol was evaluated. For quantitation of the sulfonated metabolite of salbutamol, reference material was synthesized and characterized by NMR and HRMS. Urine samples were analyzed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Salbutamol is mainly metabolized by sulfotransferase 1A3 (SULT1A3), which is most abundantly found in the jejunum. A high first pass effect occurs upon oral administration, which leads to a higher amount of salbutamol-4’-O-sulfate in urine compared to unchanged salbutamol excreted within the first hour post administration. Thus, when administered orally, the proportion of metabolite to total salbutamol was higher than for inhalative administration in the early urinary excretion. Levosalbutamol is the favored enantiomer of SULT1A3 and therefore metabolized at a higher rate whereas racemic salbutamol shows a reduced proportion between metabolite and parent compound. The amount of sulfoconjugate was found higher than that of the parent compound for all urine samples except for those excreted in the first hour after inhalative administration.

This study aimed to investigate the possibility of using one-shot hyperspectral airborne images to recognize crops for an area with many small plots. The results showed that unsupervised clustering methods could classify crops with an accuracy of 80%, which improved to 90% when restricted to only grain crops, using a single airborne hyperspectral recording. However, additional layers such as NDVI, DTM, slope, and aspect did not improve classification accuracy. For comparison, the accuracy of clustering time series Sentinel-2 images with NDVI layers and DTM-derived data yielded an accuracy of: 74% ,Sentinel-2 time series 68% and single one registration before harvest - 39%. The results of the random forest classification were slightly less accurate due to a lack of sufficient reference data. However, it is challenging to verify the reported accuracy of crop recognition in the literature above 90% due to differences in analysis methodologies, reference data selection, pixel/object approaches, metric choice, and calculation formulas used.

Development of K-Ras independence may explain failure of targeted therapy for pancreatic cancer (PC). In this paper active N as well as K-Ras was shown in all human cell lines tested. In a cell line dependent on mutant K-Ras, it was shown that depleting K-Ras reduced total Ras activity, while cell lines described as independent had no significant decline in total Ras activity. Knockdown of N-Ras showed it had an important role in controlling the relative level of oxidative metabolism but only K-Ras depletion caused a decrease in G2 cyclins, proteasome inhibition reversed this and other targets of APC/c were also decreased by K-Ras depletion. K-Ras depletion did not cause an increase in ubiquitinated G2 cyclins but instead caused exit from G2 phase to slow relative to completion of S-phase, suggesting mutant K-Ras may inhibit APC/c prior to anaphase but stabilizes G2 cyclins independently of this. We propose that during tumorigenesis, cancer cells expressing wild type N-Ras protein are selected because the protein protects cancer cells from the deleterious effects of cell cycle independent induction of cyclins by mutant K-Ras. Mutation independence results when N-Ras activity becomes adequate to drive cell division even in cells where K-Ras is inhibited. Keywords: Pancreatic Ductal Adenocarcinoma, K-Ras, N-Ras, G2 cyclins.

Plazomicin is a recently U.S. Food and Drug Administration (FDA)-approved semisynthetic aminoglycoside. Its structure consists of a sisomicin scaffold modified by adding a 2(S)-hydroxy aminobutyryl group at the N1 position and a hydroxyethyl substituent at the 6′ position. These substitutions produced a molecule refractory to most aminoglycoside-modifying enzymes. The main enzyme within this group that recognizes plazomicin as substrate is the aminoglycoside 2′-N-acetyltransferase type Ia [AAC(2′)-Ia], which reduces the antibiotic’s potency. Designing formulations that combine an antimicrobial with an inhibitor of resistance is a recognized strategy to extend the useful life of existing antibiotics. We have recently found that several metal ions inhibit acetylation of numerous aminoglycosides catalyzed by the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib]. In particular, Ag1+, which also enhances the effect of aminoglycosides by other mechanisms, is very effective in interfering with AAC(6′)-Ib-mediated resistance to amikacin. Here we report that silver acetate is a potent inhibitor of AAC(2′)-Ia-mediated acetylation of plazomicin in vitro, and it reduces resistance levels of Escherichia coli carrying aac(2′)-Ia. The resistance reversion assays produced equivalent results when the structural gene was expressed under the control of the natural or the blaTEM-1 promoters. The antibiotic effect of plazomicin in combination with silver was bactericidal, and the mix did not show significant toxicity to human embryonic kidney 293 (HEK293) cells.

In present paper, spatial Minkowski Pythagorean Hodograph (MPH) curves are characterized with Rational Rotation Minimizing Frames (RRMFs). We define Euler-Rodrigues Frame (ERF) for MPH curves and by means of this concept, we reach the definition of MPH curves of type (n, m). Expressing the conditions provided by these curves in the form of Minkowski-Hopf map that we define, it is aimed to establish a connection with the Lorentz force which occurs during the process of Computer Numerical Control (CNC) type sinker Electronic Discharge Machines (EDMs). This approach is reinforced by split quaternion polynomials. Finally, we give conditons satisfied by MPH curves of low degree to be type (n, m) and construct illustrative examples.

The results show that seven types of N-nitrosamines: N-nitrosodiethylamine (NDEA), N-Nitrosopiperidine (NPIP), N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), N-nitrosodipropylamine (NDPA), N-nitrosodibutylamine (NDBA) and N-nitrosodiphenylamine (NDphA) were reduced after heat treatment of pork steaks marinated with L. plantarum MI-LP1, S. carnosus LM-SC1, S. vitulinus LM-SV1. Selected LAB suppressed the formation of putrescine and spermine, lowered acid and peroxide values, which were significantly lower than in the control samples, then P≤0.05 in all cases. The nitrites and nitrates amounts were significantly decreased in pork steaks samples marinated with L. plantarum MI-LP1 and S. carnosus MI-SV1 strains. These results presented that selected lactic acid bacteria could be used for marinating pork steaks to improve quality characteristics and reduce N-nitrosamine formation during grilling.

N-of-1 data are unavoidable in zoological medicine. Accordingly, zoological medicine clinicians and investigators need research techniques that can make use of these data. This article reviews two methodologies for using both observational and experimental N-of-1 data: 1) systematic reviews and meta-analyses of case reports and 2) prospective N-of-1 trials. Systematic reviews of case reports and other observational evidence are formal, unbiased summaries of clinical characteristics of a particular disease-taxon combination. They offer advantages to narrative reviews by minimizing omission of relevant articles, thereby reducing the potential for mischaracterization of the literature. Meta-analyses are extensions of systematic reviews that quantitatively synthesize the data from the included articles. While valuable, systematic reviews and meta-analyses of case reports can have limited interpretations due to publication bias and confounding present in their source materials. In contrast to case reports, N-of-1 trials are prospective study designs that allow clinicians to make strong inferences about the effect of an intervention in a particular patient. They are double-blinded, single patient, multi-crossover studies that are of particular value in fields where it is difficult to recruit sufficient patients for conventional randomized control trials (RCTs), such as zoological medicine. Because they require multiple crossover periods, N-of-1 trials are ideal for evaluating short-acting interventions in patients with somewhat stable chronic diseases, such as osteoarthritis. More complex than conventional therapeutic trials, N-of-1 trials require prior consideration of how to achieve blinding, appropriate placebo controls, quantitative primary outcomes, analysis methods, and ethical approval. Aggregation of N-of-1 trials allows estimation of the average treatment effect across the population with fewer participants than a conventional RCT. While systematic reviews and meta-analyses of case reports can be used to synthesize the observational N-of-1 data already in existence, N-of-1 trials offer an exciting way to prospectively generate strong evidence that will be useful for evidence-based decision-making.

The objective of this work was to investigate the effect of different soil tillage practices in sunflower cultivation in a rotation system with intercropping Triticosecale x Pisum sativum. For this purpose a two year experimental field of 5% slope was established in central Greece. There were four treatments with three replications each. The treatments were: (a) no tillage - planting parallel to the contour (NTC-PAC), (b) conventional tillage - planting parallel to the contour (CTC-PAC), (c) no tillage - planting perpendicular to the contour (NTC-PEC), (d) conventional tillage - planting perpendicular to the contour (CTC-PEC). During the experiment plant height, leaf area index, specific leaf area, plants’ total nitrogen and plants’ proteins were measured. According to the results plant height ranged from 64.9 (CTC-PAC) to 85.2 cm (NTC-PEC) the 1st year and between 66.5 – 86.5 cm in CTC-PAC and NTC-PEC treatments in the 2nd year. Furthermore, LAI and SLA, plant’s total nitrogen and protein content and N-uptake were affected positively by the no tillage practice. To conclude, sunflower is a promising crop in a rotation system with intercropping Triticosecale x Pisum sativum, cultivating under rainfed sloping conditions.

We point out an inconsistency in Newton's equations of celestial mechanics. A set of differential equations implied by Newton's equations are shown to be free of this inconsistency. We then investigate the integrals of motion associated with this relative difference system.

Background: When homeostasis is disturbed it can occur a pathological event named inflammation. The main drugs used in the treatment consist of the non-steroidal and steroidal anti-inflammatory drugs. However, the side effects remain an obstacle during the treatments. In this work we aimed to evaluate three new regioisomers analogues of naphthyl-N-acylhydrazone derivatives. Methods: Acute models of inflammation in vivo (formalin-induced licking and carrageenan-induced inflammation) as well as in vitro were used to evaluate the effects of LASSBio-2039, LASSBio-2040, and LASSBio-2041. Results: All three substances (at 1, 10 or 30 µmol/kg) presented significant effect in the in vivo model reducing leukocyte migration, nitric oxide (NO) and interleukin-1β production. It was observed that only LASSBio-2039 significantly reduced cell migration in vitro. None of the LASSBios did affect inducible nitric oxide synthase activity nor presented NO scavenger effect. It was not observed any toxic effect neither in vivo nor in vitro. The new regioisomers analogues of naphthyl-N-acylhydrazone derivatives presented a significant anti-inflammatory activity suggesting LASSBio-2039 with a direct effect in leukocytes migratory capacity. Conclusions: Taken together the data indicate that these substances present promising effect for de development a prototype for new drugs.

The COVID-19 pandemic has highlighted the importance and urgent need of rapid and accurate diagnostic tests for detection and screening of this infection. In our proposal, a biosensor based on the ELISA immunoassay was developed for monitoring antibodies against SARS-CoV-2 in human serum samples. The SARS-CoV-2 nucleocapsid protein (N-protein) was selected as a specific receptor for the detection of SARS-CoV-2 nucleocapsid immunoglobulin G. Thus, the N-protein was immobilized on surface of screen-printed carbon electrode (SPCE) modified with carboxylated graphene (CG). The IgG-SARS-CoV-2 nucleocapsid concentration was quantified using a secondary antibody labelled with horseradish peroxidase (HRP) (anti-IgG-HRP) catalyzed by 3,3’,5,5’-tetramethylbenzidine (TMB) mediator by chronoamperometry. A linear response was obtained in the range of 1:1000-1:200 v/v in phosphate buffer solution (PBS) and the limit of detection calculated was of 1:4947 v/v. The chronoamperometric method showed electrical signals directly proportional to antibody concentrations due to Ag-Ab specific and stable binding reaction.

We recently proposed that topological quantum computing might be based on $SL(2,\mathbb{C})$ representations of the fundamental group $\pi_1(S^3\setminus K)$ for the complement of a link $K$ in the $3$-sphere. The restriction to links whose associated $SL(2,\mathbb{C})$ character variety $\mathcal{V}$ contains a Fricke surface $\kappa_d=xyz -x^2-y^2-z^2+d$ is desirable due to the connection of Fricke spaces to elementary topology. Taking $K$ as the Hopf link $L2a1$, one of the three arithmetic two-bridge links [the Whitehead link $5_1^2$, the Berge link $6_2^2$, the double-eight link $6_3^2$] or the link $7_3^2$, the $\mathcal{V}$ for those links contains the reducible component $\kappa_4$, the so-called Cayley cubic. In addition, the $\mathcal{V}$ for the later two links contains the irreducible component $\kappa_3$, or $\kappa_2$, respectively. Taking $\rho$ to be a representation with character $\kappa_d$ ($d<4$), with $|x|,|y|,|z| \le 2$, then $\rho(\pi_1)$ fixes a unique point in the hyperbolic space $\mathcal{H}_3$ and is conjugate to a $SU(2)$ representation (a qubit). Even though details on the physical implementation remain open, more generally, we show that topological quantum computing may be developed from the point of view of three-bridge links, the topology of the $4$-punctured sphere and Painlev\'e VI equation. The $0$-surgery on the $3$ circles of the Borromean rings L6a4 is taken as an example.

We solve the And\^{o} dilation problem for linear maps on vector space asked by Krishna and Johnson in \textit{[Oper. Matrices, 2022]}. More precisely, we show that any commuting linear maps on vector space can be dilated to commuting injective linear maps.

High circulating concentrations of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) are significantly associated with the risk of obesity and type 2 diabetes (T2D). We aimed at evaluating the impact of glycemic control and bariatric surgery on circulating concentrations of TMAO and its microbiota-dependent intermediate, γ-butyrobetaine (γBB), in newly diagnosed T2D patients and morbidly obese subjects. An additional experiment was carried out in eight male C57BL/6J mice fed a Western-type diet for twelve weeks. The strategy for glycemic control in the T2D patients significantly improved the HbA1c concentrations without producing changes in the estimated glomerular filtration rate. However, the plasma TMAO and γBB concentrations were significantly increased following the glycemic control in T2D patients. Bariatric surgery was very effective in reducing weight in obese subjects. Nevertheless, the surgery reduced plasma γBB concentrations without affecting TMAO concentrations and the estimated glomerular filtration rate. Neither diet-induced obesity nor insulin resistance were associated with circulating TMAO and γBB concentrations in mice. Our findings do not support that glycemic control or bariatric surgery improve the circulating concentrations of TMAO in newly diagnosed T2D and morbidly obese patients. The contribution of antidiabetic drugs to gut microbiota composition could explain TMAO elevations in treated T2D subjects.

We present results on the spontaneous crystallization of freely-jointed polymers of hard spheres obtained in an unprecedentedly long Monte Carlo (MC) simulation on a system of 54 chains of 1000 monomers. Starting from a purely amorphous configuration and after a transitory dominance of the hexagonal closed packed (HCP) polymorph, the system crystallizes in a final, stable, face centered cubic (FCC) crystal of very high perfection. Through refined metrics we gauge the degree of ordering and identify the regions of the phase transition and the corresponding morphologies. An analysis of chain conformational characteristics, of the spatial distribution of monomers and of the volume accessible to them shows that the phase transition is caused by an increase in translational entropy that is larger than the loss of conformational entropy of the chains in the crystal compared to the amorphous state. Polymer chains in the crystal adopt ideal random walk statistics as their great length renders local conformational details, imposed by the geometry of the FCC crystal, irrelevant.

The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). Newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. Regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.

Background Nitrous Oxide (N₂O) is a dissociative anaesthetic that is sometimes used recreationally. The prevalence of N₂O use is difficult to quantify but appears to be increasing. Research on N₂O harms and application of harm reduction strategies are limited. The aim of this mixed method systematic review was to collate and synthesise the disparate body of research on recreational nitrous oxide use to inform harm reduction approaches tailored for young people. Methods To identify publications reporting recreational use of N₂O, a search of public health, psychology and social science databases was conducted. Databases included PubMed, CIHNAL, PsycINFO, Scopus and Web of Science. Gray literature and Google advanced search were also used. Due to limited published literature on the recreational use of N₂O, no limit was placed on publication date or study type. A thematic synthesis extracted descriptive and analytical themes from the selected studies. Quality appraisal was conducted using the CASP Tool for Qualitative studies and the Joanna Briggs Institute case report assessment tool Results The search retrieved 407 reports. Thirty-four were included in the final analysis including sixteen case reports. The included studies were primarily concerned with raising awareness of the apparently increasing use and subsequently increasing harms of recreational N₂O use. There was limited reference to policy or legislative responses in any published studies, no suggestions for harm reduction strategies or application of service level responses. In general, individuals lack awareness of N2O related harms. Conclusion The review found three key areas that deserve further consideration including: 1) policy, 2) service delivery, and 3) harm associated with N₂O use. We recommend a top-down (policy) and bottom-up (services delivery/services users) approach to harm reduction for N₂O use which also includes further consultation and research with both groups. Future research could explore young people’s experience of N₂O use including benefits and problems to inform contextually relevant harm reduction strategies.

This article analyzes and compares the integration of two different maximum power point tracking (MPPT) control methods, which are tested under partial shading and fast ramp conditions. These MPPT methods are designed by Improved Particle Swarm Optimization (IPSO) and a combination technique between Neural Network and Perturb & Observe method (NN_P&O). These two methods are implemented and simulated for photovoltaic systems (PV), where various system responses, such as: voltage and power are obtained. The MPPT techniques were simulated using Matlab/Simulink environment. A comparison of the performance of IPSO and NN_P&O algorithms is carried out to confirm the best accomplishment of the two methods in terms of speed, accuracy and simplicity.

The C/N ratio is an extremely important parameter in the composting process, which is directly responsible for the growth of microorganisms. A low C/N ratio contributes to higher emissions of greenhouse gases and odorous substances, such as ammonia (NH3), which is formed by nitrogen mineralization. Due to the highly toxic effects of ammonia, it is a particularly unwanted by-product that can disrupt the composting process because it poisons microorganisms and cause environmental issues. The activity of anammox bacteria, so far analyzed only in wastewater treatment processes, is a particularly efficient method of nitrogen removal, having an advantage over the conventional methods used previously. Our study proofs the presence of anammox bacteria during composting, what gives an opportunity to improve the process and reduce its impact on atmospheric pollution. Despite the aerobic nature of this process, the composted mass of waste presents conditions conducive to the development of these ammonia oxidizing bacteria, as well as other strains of microorganisms cooperating with them. This makes it possible to compost at a low C/N ratio; in addition, there is no need for additional energy supply through aeration, as the processes carried out by anammox bacteria do not require oxygen.

Both SARS-CoV-2 and SARS-CoV initially appeared in China and spread to other parts of the world. SARS-CoV-2 has generated a COVID-19 pandemic causing more than 6 million human deaths worldwide while the SARS outbreak quickly ended in six months with a global total of 774 reported deaths. One of the factors contributing to this stunning difference in the outcome between these two outbreaks is the inaccuracy of the RT-qPCR tests for SARS-CoV-2, which generated a large number of false-negative and false-positive test results that have misled patient management and public health policy-makers. This article presented Sanger sequencing evidence to show that the RT-PCR diagnostic protocol established in 2003 for SARS-CoV can in fact detect SARS-CoV-2 accurately due to the well-known nonspecific PCR amplification of DNAs with similar sequences. Using nested RT-PCR followed by Sanger sequencing to retest 50 patient samples collected in January, 2022 and sold as RT-qPCR positive reference confirmed 21 (42%) were false-positive. Although the other 29 positive isolates were categorized as Omicron variant by partial sequencing of the N gene, and the RBD and the NTD of the S gene, 9 (31%) showed focal to complete sequencing failure in the S gene segments due to multi-allelic SNPs. During the course of the study, an Omicron variant isolate containing a BA.1 NTD and a BA.2 RBD in its S gene was also detected. Routine partial S gene sequencing of all PCR-positive samples can timely discover multi-allelic SNPs and viral recombination in the circulating variants for investigation of their impacts on vaccine efficacies, therapeutics and diagnostics.

The seasonal and vertical spatial variation characteristics of total N, NH4+—N and NO3-—N in the soil in Picea mongolica forest at different stand ages were studied. The results showed that: (1) NH4+ —N in the soil in Picea mongolica forest was positively correlated with sample date, soil NO3-—N and forest age (P <0.05), and negatively correlated with soil depth (P < 0.01). NO3-—N in the soil in Picea mongolica forest was negatively correlated with sample date and forest age (P < 0.05), and significantly negatively correlated with soil depth (P < 0.01); (2) the content of NH4+—N is greater than that of NO3-—N in each soil layer of Picea mongolica forest at three forest ages. The correlation analysis showed which had an impact on the content of NH4+—N and NO3-—N in the soil in Picea mongolica forest. The content was lower in February and November, and higher in May and August；(3) The contents of total N, NH4+—N and NO3-—N in the soil of Picea mongolica forest in the three forest ages increased with the depth of soil layer (0-50cm), and showed an overall downward trend. The contents of NH4+—N in the soil layer of young forest (0-10cm, 10-20cm and 20-30cm, 30-40cm and 40-50cm) were significantly different (P＜0.05), and the contents of NO3-—N were also significantly different (P＜0.05), while their contents of middle-aged forest and near mature forest increased with the depth of soil layer, There was no significant difference in the content of NH4+—N; (4) The content of NH4+—N in the soil in Picea mongolica forest generally showed the following change trend near mature forest > middle-aged forest > young forest. The change trend of soil NO3-—N content is consistent with that of the content of NH4+—N in the soil in Picea mongolica forest.

The cytosolic PNGase (peptide:N-glycanase; Png1 in yeast; NGLY1/Ngly1 in human/mice), also known as peptide-N4-(N-acetyl-beta-glucosaminyl)-asparagine ami-dase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-D-glucosaminyl) asparagine residue into N-acetyl-β-D-glucosaminylamine and a peptide containing an aspartate residue. This enzyme (NGLY1) plays essential roles in clearance of misfolded or unassembled gly-coproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive hu-man genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP path-way, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review indeed uncovers the detailed NGLY1’s structure and its im-portant roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency.

The fatigue life of welded joints under cyclic loading is a complex process that can be roughly divided into fatigue crack initiation, crack propagation and final fracture. Usually, these phases are evaluated separately. Several methods are available to estimate the extent of the different phases in welded components, such as stress-based fatigue concepts for crack initiation or linear elastic fracture mechanics for crack propagation; however, distinguishing these phases in welded components is a complex procedure and often relies on assumptions such as transition crack sizes. The objective of this study is to investigate the relationship between fatigue crack initiation and propagation in welded joints using artificially notched specimens with welded joints characteristics of different notch acuity (different radii and opening angle). The experiments show that the investigated relationship basically depends on the notch acuity, the load level and the stress ratio.

Home-field advantage (HFA) encompasses all the processes leading to faster litter decomposition in the 'home' environment as compared to that of ‘away’ environments. To determine the occurrence of HFA in a forest and adjacent clear-cut, we set up a reciprocal litter decomposition experiment within the forest and clear-cut for two soil types (Cambisols and Gleysols) in temperate Germany. The forest was dominated by Norway spruce (Picea abies), whereas forest regeneration of European Beech (Fagus sylvatica) after clearcutting was encouraged. Our observation that Norway spruce decomposed faster than European beech in 70-yr-old spruce forest, was therefore most likely related to specialized litter-microbial interaction under existing spruce, and leading to a HFA. The ‘spruce’ microbial biome and soil conditions of original forest were then rapidly changed even after a short-term regeneration following clearcutting, resulting in faster beech decomposition also masking any HFA for spruce, particularly in moisture- and nutrient-deficient Cambisols. Divergence between forest and clear-cut in the Cambisol of their litter δ15N values beyond 9 months, implied litter N decomposition was only initially independent of soil and residual C status. We conclude that clearcutting modifies HFA and helps promote the establishment or regeneration of European beech in this and similar forest mountain upland areas.

Among the first discovered and most prominent cellular oncogenes is MYC, which encodes a bHLH-ZIP transcription factor (Myc) that both activates and suppresses numerous genes involved in proliferation, energy production, metabolism and translation. Myc belongs to a small group of bHLH-ZIP transcriptional regulators (the Myc Network) that includes its obligate heterodimerization partner Max and six “Mxd proteins” (Mxd1-4, Mnt and Mga) each of which heterodimerizes with Max and largely oppose Myc’s functions. More recently, a second group of bHLH-ZIP proteins (the Mlx Network) has emerged. It is comprised of the Myc-like factors ChREBP and MondoA, which, in association with the Max-like member Mlx, regulate smaller and more functionally restricted sets of target genes, some of which are shared with Myc. Opposing ChREBP and MondoA are heterodimers comprised of Mlx and Mxd1, Mxd4 and Mnt, which also structurally and operationally link the two Networks. We discuss here the functions of these “Extended Myc Network” members with particular emphasis on the roles played by Max, Mlx and Mxd proteins in suppressing normal and neoplastic growth. These roles are complex due to the temporally- and tissue-restricted expression of Extended Myc Network proteins in normal cells, their regulation of both common and unique target genes and, in some cases, their functional redundancy.

Hantaviruses are enveloped viruses that possess a tri-segmented, negative-sense RNA genome. The viral S-segment encodes the multifunctional nucleocapsid protein (N), which is involved in genome packaging, intracellular protein transport, immunoregulation and several other crucial processes during hantavirus infection. In this study we have generated fluorescently tagged N protein constructs derived from Puumalavirus, the dominant hantavirus species in Central, Northern and Eastern Europe. We have comprehensively characterized this protein in the rodent cell line CHO-K1, monitoring the dynamics of N protein complex formation and investigating co-localization with host proteins as well as the viral glycoproteins Gc and Gn. We found a significant spatial correlation of N with vimentin, actin and P-bodies, but not with microtubules. N constructs also co-localized with Gn and Gc, albeit not as strong as the glycoproteins associated with each other. Moreover, we as-sessed oligomerization of N constructs, observing efficient and concentration-dependent multi-merization, with complexes comprising more than 10 individual proteins.

The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, which precluded its direct repurposing against malaria. The targeted N-alkylation of nor-DXM 15 delivered a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2’-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory potency compared to tazopsine 1 and DXM 3 against parasite liver and blood stages, with 760 ± 130 nM and 2.1 ± 0.4 µM IC50 values, respectively, as well as liver/blood phase selectivity of 2.8. Furthermore, cpd. 16i showed a 5 to 8-fold increase of activity relatively to DXM 3 against P. falciparum stages I-II and V gametocytes, with 18.5 µM and 13.2 µM IC50 values, respectively. Cpd. 16i can thus be considered a promising novel hit compound against malaria in the ent-morphinan series with putative pan-cycle activity, paving the way for further therapeutic development (e. g., investigation of its prophylactic activity in a mouse model of malaria).