This dissertation presents a method for the synthesis of substituted indoles bearing heterocyclic substituents onto the 3- position. The route for the synthesis of the heterocyclic substituents indoles starts from 3-acetyl indole nucleus depend on two parts. One part: Reaction of 3-acetylindole 1 with hydrazide compounds such as phenyl hydrazine, hydrazine hydrate, and thio-semicarbazide, to yield 3-(1-(2-phenylhydrazono) ethyl)-1H-indole 2, 3-(1-hydrazonoethyl)-1H-indole 6, and thiosemicarbazone 10 respectively. 3-(1-Hydrazonoethyl)-1H-indole 6 reacted with thiophene-2-carboxaldeyde, isatin and 3-acetyl indole. In the same way, 3-(1-(2-phenylhydrazono) ethyl)-1H-indole 2 reacted with thioglycollic acid, glycine and benzaldehyde. 3-Acetylindole 1 thiosemicarbazone reacted with acetic anhydride, piperidine, concentration of hydrochloric acid and thiophene-2-carboxaldeyde. Second part. Reaction of 3-acetyl indole 1 with amines compounds such as p-nitroaniline to formed Schiff base 15 which it reacted with thioglycollic acid to give compound 16. 3-Acetyl indole 1 reacted with ethylene diamine to afford bis imine indole to afford compound 17. The reports of this docking study revealed that the new compounds exhibit good antibacterial activity. The synthesized compounds screened in vitro for their antibacterial activity revealed remarkable inhibitory effects against the selected microorganisms. And also an anti-oxidant activity studying for some synthesized compounds. Structures of the newly synthesized compounds examination by spectral data (IR, 1H- NMR and 13C -NMR).

Fusarium culmorum is a major pathogen of grain crops. Infected plants accumulate deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON), or nivalenol (NIV), which are mycotoxins of the trichothecene B group. These toxins are also produced by F. graminearum species complex. New trichothecenes structurally similar to trichothecenes B but lacking the carbonyl group on C-8, designated NX toxins, were recently discovered in atypical isolates of F. graminearum from North America. Only these isolates and a few strains of a yet to be characterized Fusarium species from South Africa are known to produce NX-2 and other NX toxins. Here we report that among 20 F. culmorum strains isolated from maize, wheat, and oat in Europe and Asia over a period of 70 years, 18 strains produced NX-2 simultaneously with 3-ADON and DON or NIV. Rice cultures of strains producing 3-ADON accumulated NX-2 in amounts corresponding to 2-8% of 3-ADON (1.2 - 36 mg/kg). A strain producing NIV accumulated NX-2 and NIV at comparable amounts (13.6 and 10.3 mg/kg, respectively). In F. graminearum, producers of NX-2 possess a special variant of cytochrome P450 monooxygenase encoded by TRI1 that is unable to oxidize C-8. In F. culmorum, producers and nonproducers of NX-2 possess identical TRI1; the reason for the production of NX-2 is unknown. Our results indicate that production of NX-2 simultaneously with trichothecenes B is a common feature of F. culmorum.

The major auxin, indole-3-acetic acid (IAA), is associated with a plethora of growth and developmental processes including embryo development, expansion growth, cambial activity, and the induction of lateral root growth. Accumulation of the auxin precursor indole-3-acetamide (IAM) induces stress related processes by stimulating abscisic acid (ABA) biosynthesis. How IAM signaling is controlled is, at present, unclear. Here, we characterize an ami1/rooty double mutant, that we initially generated to study the metabolic and phenotypic consequences of a genetic blockade of the indole glucosinolate and IAM pathways in Arabidopsis thaliana. Our mass spectrometric analyses of the mutant revealed that the combination of the two mutations is not sufficient to fully prevent the conversion of IAM to IAA. The detected strong accumulation of IAM was, however, recognized to substantially impair seed development. We further show by genome-wide expression studies that the double mutant is broadly affected in its translational capacity, and that a small number of cell proliferation and plant growth regulating transcriptional circuits are repressed by the high IAM content in the seed. In accordance with the previously described growth reduction in response to elevated IAM levels, our data support the hypothesis that IAM is a growth repressing counterpart to IAA.

Bacterial indole-3-acetic acid (IAA), an effector molecule in microbial physiology, plays an important role in plant growth-promotion. Here, we comprehensively analyzed about 7282 prokaryotic genomes representing diverse bacterial phyla, combined with root-associated metagenomic data to unravel the distribution of tryptophan-dependent IAA synthesis pathways and to quantify the IAA synthesis-related genes in the plant root environments. We found that 82.2% of the analyzed bacterial genomes were potentially capable of synthesizing IAA from tryptophan (Trp) or intermediates. Interestingly, several phylogenetically diverse bacteria showed a preferential tendency to utilize different pathways and tryptamine and indole-3-pyruvate pathways are most prevalent in bacteria. About 45.3% of the studied genomes displayed multiple coexisting pathways, constituting complex IAA synthesis systems. Furthermore, root-associated metagenomic analyses revealed that rhizobacteria mainly synthesize IAA via IAM and tryptamine (TMP) pathways and might possess stronger IAA synthesis abilities than bacteria colonizing other environments. The obtained results refurbished our understanding of bacterial IAA synthesis pathways and provided a faster and less labor-intensive alternative to physiological screening based on genome collections. The better understanding of IAA synthesis among bacterial communities could maximize the utilization of bacterial IAA to augment the crop growth and physiological function.

Lectins, characterized by their carbohydrate-binding ability, have an extensive practical application. However, their industrial use is limited by low yields, and few active recombinant lectins have been reported. In this study, the algal lectin BPL-3 (Bryopsis plumosa lectin 3) was successfully produced using a bacterial expression system, BL21(DE3), with an artificial repeated structure (dimeric construct). Recombinant dimeric BPL3 (rD2BPL3) was confirmed by LC-MS/MS spectrometry. Expression efficiency was greater for the construct with the repeat structure (rD2BPL3) than the monomeric form (rD1BPL3). Optimal conditions for expression were 1 mM IPTG at 20 °C. Recombinant lectin was purified under denaturing conditions and refolded by the flash dilution method. Recombinant BPL3 was solubilized in 1× PBS containing 2 M urea. rD2BPL3 showed strong hemagglutination activity using human erythrocytes, similar to that of native BPL3. rD2BPL3 had a similar sugar specificity to that of the native protein, i.e., to N-acetyl-glucosamine (GlcNAc) and N-acetyl-galactosamine (GalNAc). Glycan array results showed that recombinant BPL3 and native BPL3 exhibited different binding properties. Both showed weak binding activity to α-Man-Sp. Native BPL3 showed strong binding specificity to the alpha conformation of amino sugars, and rD2BPL3 had binding activity to the beta conformation. The process developed in this study was suitable for the quality-controlled production of high amounts of soluble recombinant lectins.

Indole-3-acetic acid (IAA) is a key vegetative hormone that plays crucial roles in plant growth and development. In this study, the effect of the exogenous application of IAA as a biostimulant in the cultivation of onions (Allium cepa) was investigated. Different IAA concentrations were evaluated to determine their effects on onion growth and chemical parameters. Various physical and chemical parameters such as total fresh weight, plant height, chlorophyll content, nitrates, total phenols, and antioxidant capacity (DPPH) were analyzed. The results revealed that exogenous application of IAA had a significant impact on onion growth and quality. Specifically, it was found that certain concentrations of IAA fostered a greater fresh weight of the bulb, an increase in the levels of phenolic compounds and a greater DPPH. However, the onion response to IAA was dependent on the concentration. In conclusion, the present study provides evidence that the exogenous application of IAA as a biostimulant can improve onion growth and quality. These results are relevant for the development of sustainable agricultural practices and could be oriented towards crop improvement.

The presence of exogenous auxins such as indole-3-acetic acid (IAA), has been reported in organic materials such as vermicompost. The objectives of this work were to quantify the concentration of IAA in sand-based substrates with vermicompost (S-VC), to establish the relationship between the concentration of exogenous IAA and the amount of vermicompost (VC), as well as determine its influence on the development of tomato plants. S-VC substrates with different percentages based on volume (0, 20, 40 and 50% VC) placed in pots were used to transplant tomato seedlings. In each substrate, the concentration of IAA was determined at the beginning and at the end of a culture cycle, as well as the bacterial load. In addition, some performance components were measured in the plants. The results show that by increasing 1 kg of VC in a sand-based substrate, the concentration of exogenous IAA increases both at the beginning and at the end of the experiment (0.0470 and 0.0642 mg g^-1, respectively); a result that, in turn, was related to the colony-forming units of gram-positive bacteria (Bacillus spp., mainly). Behavior that is reflected in tomato plants; for example, the root had its maximum development (371.33 cm^-3) when the amount of VC in the substrate was 4.12 kg.

Reactions of quinones with compounds containing an amino group can produce a wide variety of addition or substitution products that depend on reactivity of both quinone and amino derivative. 6,7-Dichloropyrido[1,2-a]benzimidazole-8,9-diones undergo selective nucleophilic substitution reaction with different benzohydrazides and α-hydroxy-p-quinone imine derivatives stabilized by strong intramolecular hydrogen bond were isolated. Synthesized compounds represent a combination of several structural motifs: benzimidazole core fused with α-hydroxy-p-quinone imine which contains a benzamido fragment. The protonation/deprotonation processes were investigated in a solution using UV-Vis spectroscopy and 1H NMR titration experiment. X-ray crystallography analysis revealed a set of weak non-covalent interactions such as intra- and intermolecular hydrogen bonds and π-π stacking. Additionally, the redox behavior of 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione and its p-imino derivative was investigated in acidic and neutral environment using cyclic voltammetry measurements. Cathode material based on 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione could act as potential effective active electrode in aqueous electrolyte batteries, however further optimization is required.

The indole nucleus is an important element of many natural and synthetic molecules with significant biological activity. Nonetheless, the co-presence of transitional metals in organic scaffold may represent an important factor in the development of effective medicinal agents. This review covers some of the relevant and recent achievements in the biological, chemical and pharmacological activity of important indole-based metal complexes in the area of drug discovery.

Indole is a versatile pharmacophore widely distributed in bioactive natural products. This privileged scaffold has been found in a variety of molecules isolated from marine organisms such as algae and sponges. Among these, indole alkaloids represent one of the biggest, most promising family of compounds, having shown a wide range of pharmacological properties, including anti-inflammatory, antiviral and anticancer activities. The aim of this review is to show the current scenario of marine indole alkaloid derivatives, covering not only the most common chemical structures, but also new synthetic routes developed during the last years as well as promising therapeutic applications.

Pore structure characterization and fractal analysis have great significance for understanding and evaluating tight limestone reservoirs. In this work, the pore structure of tight limestone is characterized combined with low-temperature nitrogen adsorption (LTNA) and low-field nuclear magnetic resonance (NMR), and the fractal dimension of tight limestone pore structure is discussed based on LTNA and NMR data. The results indicate that the pores of tight limestone have H3 and H4 types, the pore size distribution (PSD) of H3 type is a wave distribution ranging from 2 to 10 nm, and the PSD of H4 type is a unimodal distribution ranging from 2 to 10 nm. The transverse relaxation time (T2) spectrum of tight limestone shows single peak (DF), double peak (SF) and three peak (TF), and the T2 spectrums for micropores, mesopores and macropores range from 0.1 to 10 ms, from 10 to 100 ms, and greater than 100 ms, respectively. The LTNA fractal dimension of tight limestone (DL) ranges between 2.4446 and 2.7688, with an average of 2.5729, and the NMR fractal dimensions of micropores (DNMR1), mesopores (DNMR2) and macropores (DNMR3) are distributed between 0.3744 to 1.1293, 2.4263 to 2.9395 and 2.6582 to 2.9989, respectively. Moreover, there is no correlation between fractal dimension and permeability and porosity, a negative correlation between DL and average pore radius, a positive correlation between DL and specific surface area, and a positive correlation between DNMR2 and DNMR3 and micropore content, while DNMR2 and DNMR3 are negatively correlated with the content of mesopores and macropores.

A Cu₂ZnSnS₄ (CZTS) film with a thickness of approximately 1.5 μm was fabricated on a Mo-coated glass substrate by annealing a CZTS precursor fabricated from nanoparticle ink. The chemical states of the elements in the CZTS thin film in the depth direction were studied to identify the presence of secondary phases, which are detrimental to the performance of solar cells containing CZTS. X-ray diffraction was unable to detect any secondary phases in CZTS because of their small relative amount. Instead, X-ray photoelectron spectroscopy (XPS), which is highly sensitive to chemical state, was conducted at different depths in the CZTS film to further check the presence of secondary phases. XPS analysis revealed peaks shift consistent with the presence of secondary phases. For the CZTS film annealed in a S atmosphere at 575 °C for 3 h, the film surface consisted of a secondary-phase layer composed of CuS, ZnS, and SnSx (x=1 or 2) originating from the decomposition of CZTS. At depths below 80 nm, the film was pure CZTS. Formation of MoS2 at the CZTS–Mo interface was confirmed by XPS analysis of Mo and S.

A Q-switched Nd:YAG laser was focused on Pb-Ti alloy samples in several Laser Induced Breakdown experiments in order to measure the Stark parameters of several spectral lines (58) of single ionized Titanium including the 3504.89 Å, and the 3510.83 Ålines (where we aported new experimental and theoretical values).Diagnostics of the laser induced plasmas (electron density and electron temperature) was performed using Balmer’s H alpha line (6562.7 Å).Temperatures were obtained by the Boltzmann Plot technique with spectral lines of Pb I (after correction for its evident self-absorption).Subsequently, calculations by the Griem approach of the Stark broadening parameters for several spectral lines were performed using the Gaunt factors proposed by Van Regemorter and those proposed by Douglas H. Sampson. In the latter cases the values obtained were very close to the experimental values. It allows us to assume that the calculations made for the spectral lines of Ti II, without experimental information, are more accurate using the Gaunt factors proposed by Sampson.

This study addresses the urgent need for sustainable protein sources in aquaculture due to the depletion of marine resources and rising costs. Animal protein sources, particularly poultry by-product meal (PBM) and insect exuviae meal, are investigated as viable alternatives to fishmeal (FM). Research confirms the successful replacement of FM with a combination of PBM and insect exuviae meal (up to 50%) in the diet of European seabass without compromising growth, feed conversion, gut health and liver fat content. In particular, growth performance was robust with both PBM formulations, with the 25% PBM diet showing better results. Histological examinations showed good gut and liver health, contradicting the concerns of previous studies. The study emphasizes the importance of holistic analyzes that go beyond growth parameters and include histomorphological investigations. The results show that PBM in combination with insect/exuviae meal is well tolerated by seabass, which is consistent with literature reports of mitigating negative effects on gut health. A detailed analysis of the microbiota revealed a decrease in the Firmicutes/Proteobacteria ratio due to an increase in potentially pathogenic bacteria. However, the formulation containing insect exuviae partially counteracted this effect by preserving the beneficial Lactobacillus and promoting the synthesis of short-chain fatty acids (SCFA), particularly butyrate. Chitin-rich components from insect exuviae were associated with improved gut health, which was supported by increased production of SCFA, which are known for their anti-inflammatory properties. The study concludes that a combination of PBM and insect/exuviae meal can replace up to 50% of FM in the diet of seabass, supporting sustainable aquaculture practices. Despite some changes in the microbiota, the negative effects are mitigated by the addition of insect exuviae, highlighting their potential as a prebiotic to increase fish productivity and contribute to a circular economy in aquaculture.

The treatment of the bulky Rind-based dibromosilanes, (Rind)2SiBr2 (2) [Rind = 1,1,7,7-tetra-R1-3,3,5,5-tetra-R2-s-hydrindacen-4-yl: EMind (a: R1 = Et, R2 = Me) and Eind (b: R1 = R2 = Et)], with two equivalents of tBuLi in Et2O at low temperatures resulted in the formation of blue solutions derived from the diarylsilylenes, (Rind)2Si: (3). Upon warming the solutions above −20 °C, the blue color gradually faded, accompanying the decomposition of 3 and yielding the cyclic hydrosilanes (4) via intramolecular C−H bond insertion at the Si(II) center. The molecular structures of the bulky Eind-based 3b and 4b were confirmed by X-ray crystallography. Thus, at −20 °C, blue crystals were formed (Crystal-A), which were identified as mixed crystals of 3b and 4b. Additionally, colorless crystals of 4b as a singular component were isolated (Crystal-B), whose structure was also determined by an X-ray diffraction analysis. Although the isolation of 3 was difficult due to their thermally-labile nature, their structural characteristics and electronic properties were discussed based on the experimental findings complemented by computational results. We also examined the hydrolysis of 3b to afford the silanol, (Eind)2SiH(OH) (5b).

A series of novel indole Schiff base derivatives (2a–2t) containing a 1,3,4-thiadiazole scaffold modified with a thioether group were synthesized, and their structures were confirmed using FT-IR, ¹H NMR, ¹³C NMR, andHR-MS. In addition, the antifungal activity of synthesized indole derivatives was investigated against Fusarium graminearum (F. graminearum), Fusarium oxysporum (F. oxysporum), Fusarium moniliforme (F. moniliforme), Curvularia lunata (C. lunata), and Phytophthora parasitica var. nicotiana (P. p. var. nicotianae) using the mycelium growth rate method. Among the synthesized indole derivatives, compound 2j showed the highest inhibition rates of 100%, 95.7%, 89%, and 76.5% at a concentration of 500 μg/mL against F. graminearum, F. oxysporum, F. moniliforme, and P. p. var. nicotianae, respectively. Similarly, compounds 2j and 2q exhibited higher inhibition rates of 81.9% and 83.7% at a concentration of 500 μg/mL against C. lunata. In addition, compound 2j has been recognized as a potential compound for further investigation in the field of fungicides.

To stabilize the Earth’s climate a large-scale transition is needed to non-carbon emitting renewable energy technologies like wind and solar energy. Although these renewable energy sources are now lower-cost than fossil fuels, their inherent intermittency make them unable to supply a constant load without storage. To address these challenges rechargeable electric batteries are currently the most promising option; however, their high capital costs limit current deployment velocities. To both reduce the cost as well as improve performance 3D printing technology has emerged as a promising solution. This literature review provides the state-of-the-art enhancements of battery properties with 3D printing including efficiency, mechanical stability, energy and power density, customizability and sizing, production process efficiency, material conservation and environmental sustainability as well as the progress in solid-state batteries. The principles, advantages, limitations, and recent advancements associated with the most common types of 3D printing are reviewed focusing on their contributions to the battery field. 3D printing batteries offer design flexibility, material flexibility, reduces pack weight, minimizes material waste, increases the range of applications and has the potential to reduce costs. As 3D printing technologies become more accessible, the prospect of cost-effective production for customized batteries is extremely promising.

Healthcare professionals constantly face situations that reflect ecosystems’ degradation. These can negatively affect their mental health. Research suggests that hope and resilience can play an important role in this scenario, since they are related to/predict mental health in highly heterogeneous samples (considering geography, age, profession, health, etc.). In this context, the aims of the present study are: to characterize and explore the relationship between hope, resilient coping and mental health of Portuguese healthcare professionals. Using Google Forms, 276 healthcare professionals answered to the GHQ-28, the (adult) Trait Hope Scale, and the Brief Resilient Coping Scale (cross-sectional study). The minimum and maximum possible scores were reached, with the exception of the maximum score of GHQ-28-Total. Regarding Hope, 19.6% scored below the midpoint (M=43.46, SD=11.97); 29.3% revealed low resilience (M=14.93, SD=4.05); and the average of 4 of the 5 Mental Health scores (exception: Severe Depression) indicates the probability of a psychiatric case. Hope correlated with Social Dysfunction and GHQ-28-Total; resilient coping proved to be a (weak) predictor of 4 of the 5 GHQ-28 indicators (exception: Severe depression). The results support the need to promote the sample's mental health, hope and resilient coping. They also suggest that stimulating resilient coping may contribute to improving healthcare professionals’ mental health.

The present study was performed to examine that transforming growth factor beta (TGF-β) in root-surrounding tissues on deciduous teeth during the physiological root resorption regulates the differentiation induction into odontoclast. We prepared root-surrounding tissues with (R) or without (N) physiological root resorption scraped off at three regions (R1-R3 or N1-N3) from the cervical area to the apical area of the tooth and measured both TGF-β and the tartrate-resistant acid phosphatase (TRAP) activities. The TGF-β activity level was increased in N1-N3, whereas the TRAP activity was increased in R2 and R3. In vitro experiments for RANKL-mediated osteoclast differentiation revealed that TGF-β in N1-N3 and R1-R3 enhanced the TRAP activity in RAW264 cells. A genetic study indicated that the mRNA level of TGF-β1 in N1 and N2 was significantly increased, and corresponded with that of osteoprotegerin (OPG). In contrast, the expression level of receptor activator of NF-κB ligand (RANKL) was increased in R2 and R3. Our findings suggest that TGF-β is closely related to the regulation of OPG induction and RANKL-mediated odontoclast differentiation depending on the timing of RANKL and OPG mRNA expression in the root-surrounding tissues of deciduous teeth during physiological root resorption.

Advanced glycation end-products (AGEs) form through non-enzymatic glycation of various proteins. Optic nerve degeneration is a frequent complication of diabetes, and retinal AGEs accumulation is strongly linked to diabetic retinopathy development. Type 2 diabetes mellitus (T2DM) is a major risk factor for Alzheimer's disease (AD), with patients often exhibiting optic axon degeneration in the nerve fiber layer. Notably, a gap exists in our understanding of how AGEs contribute to neuronal degeneration in the optic nerve within the context of both diabetes and AD. Our previous work demonstrated that glyceraldehyde (GA)-derived toxic advanced glycation end-products (TAGE) disrupt neurite outgrowth through TAGE-β-tubulin aggregation and tau phosphorylation in neural cultures. In this study, we further illustrated GA-induced suppression of optic nerve axonal elongation via abnormal β-tubulin aggregation in mouse retinas. Elucidating this optic nerve degeneration mechanism holds promise for bridging the knowledge gap regarding vision loss associated with DM and AD.

Aquifer Thermal Energy Storage (ATES) systems are garnering attention as high-efficiency air conditioning technologies that contribute to the realization of a carbon-neutral society. This study focuses on an ATES system constructed in Japan, characterized by its complex geological conditions and thin aquifer layers. Through performance analysis using four years of operational data, we achieved a Coefficient of Performance (COP) of 5 on the building load side. This paper confirms the equivalence of the dimensionless production temperature and heat recovery rate, observing nearly identical changes in the dimensionless production temperature over four cycles (eight seasons). Furthermore, we propose an operational method for the following fiscal year that maintains the balance between accumulated storage quantity and pumping volume, based on predictions from this plant's operational pattern.

Enzymatic polyethylene terephthalate (PET) recycling processes are gaining interest for their low environmental impact, use of mild conditions, and specificity. Furthermore, PET hydrolase enzymes are continuously being discovered and engineered. In this work, we studied a PET hydrolase (PET2), initially characterized as an alkaline thermostable lipase. PET2 was produced in a fusion form with a 6-histidine tag in the N-terminal. The PET2 activity on aromatic terephthalate and new indole-based polyesters was evaluated using polymers in powder form. Compared with IsPETase, an enzyme derived from Ideonella sakaiensis, PET2 showed a lower PET depolymerization yield. However, interestingly, PET2 gave significantly higher polybutylene terephthalate (PBT) and polyhexylene terephthalate (PHT) depolymerization yields. A clear preference was found for aromatic indole-derived polyesters over non-aromatic ones. No activity was detected on Akestra™, an amorphous copolyester with spiroacetal structures. Docking studies suggest that a narrower and more hydrophobic active site reduces its activity on PET but favours its interaction with PBT and PHT. Understanding the enzyme preferences of polymers will contribute to their effective use to depolymerize different types of polyesters.

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes owing to COVID-19 include QT prolongation and ST-T changes; however, there have been no studies on ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24-h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 a 76-year-old man with hypertension and diabetes, and Case 3 a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. LP, TWA, HRV, and HRT were all positive in three cases with no significant structural cardiac disease at the initial phase of admission. There is a possibility that LP, TWA, HRV, and HRT have the potential to be risk stratifiers of COVID-19 pneumonia in the early phase of admission. Further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed.

Dust storms play a crucial role in the climate system and the space environment of Mars and have a great impact on human’s Mars exploration activities. The Martian dust storms exhibit significant regional, seasonal and interannual variations due to various controlling factors such as the large-scale atmospheric circulation, varying solar radiation forcing, and Martial orbital and rotational motions and their coupling to the atmospheric dynamics. This paper focuses on the review of cur-rent understandings on Martian dust storms. This paper begins by elucidating the basic properties of dust storms, and their driving mechanisms and impacts on atmospheric dynamics, atmospheric electric property, space environment, topography, and Mars explorations. Then it introduces the observation methods on different platforms including orbiters and landers/rovers, and the da-tasets constructed based on these historical observations for Martian dust storms. Finally, we pro-posed the dust storm monitoring and forecasting for the upcoming Chinese Tianwen-3 Mars sam-pling returning mission. It concludes by depicting the future research topics to systematically un-derstand the Martian dust storms.

The ubiquitous presence of microplastics (MPs) in the environment poses a threat to ecosystems and increases concerns about their exposure to the human body. However, despite being consumed for health improvement, limited research has been conducted on MPs in functional foods. This study aimed to investigate the occurrence of MPs and the relation of the source of raw material or the manufacture in various omega-3 oil in the Korean market. MPs in omega-3 capsule and raw oil, sourced from both plant-based (PB) and animal-based (AB) sources, were investigated. We developed the method by direct filtration with acetone washing and analyzed MPs greater than 5 μm using microscope-Raman spectroscopy. The average number of MPs was found to be 1.2 ± 1.7 MPs/g for PB raw oil, 2.2 ± 1.7 MPs/g for AB raw oil, 3.5 ± 3.9 MPs/g for PB capsule oil, and 10.6 ± 8.9 MPs/g for AB capsule oil. Polypropylene and polyethylene terephthalate were major specious (83-95 %) found in omega-3 oil. The ratio of size range remained consistent across all groups, with a trend of higher detection rates as the size diminished. The results reveal that the main reason of MPs contamination is not the source of raw material but the manufacturing and packaging process for omega-3 oil.

The Bcl-2 family plays a crucial role in regulating cell apoptosis, making it an attractive target for cancer therapy. In this study, a series of indole-based compounds, U1-6, were designed, synthesized, and evaluated for their anticancer activity against BCL-2-expressing cancer cell lines. The binding affinity, safety profile, cell cycle arrest, and apoptosis effects of the compounds were tested. The designed compounds exhibited potent inhibitory activity at sub-micromolar IC50 concentrations against MCF-7, MDA-MB-231, and A549 cell lines. Notably, U2 and U3 demonstrated the highest activity, particularly against MCF-7 cells. Respectively, both U2 and U3 showed potential Bcl-2 inhibition activity with IC50 values of 1.2 ± 0.02 and 11.10 ± 0.07 µM using an ELISA binding assay compared to 0.62 ± 0.01 µM for gossypol, employed as positive control. Molecular docking analysis suggested stable interactions of compound U2 at the Bcl-2 binding site through hydrogen bonding, pi-pi stacking, and hydrophobic interactions. Furthermore, U2 demonstrated significant induction of apoptosis and cell cycle arrest at G1/S phase. Importantly, U2 displayed a favorable safety profile on HDF human dermal normal fibroblast cells at 10-fold greater IC50 compared to MDA-MB-231 cells. These findings underscore the therapeutic potential of compound U2 as a Bcl-2 inhibitor and provide insights into its molecular mechanisms of action.

Tryptophan metabolism, via the kynurenine (Kyn) pathway, and microbial transformation of tryptophan to indolic compounds, are fundamental for host health; both of which are altered in colon carcinogenesis. Alterations in tryptophan metabolism begin early in colon carcinogenesis as an adaptive mechanism for the tumor to escape immune surveillance and metastasize. The microbial community is a key part of the tumor microenvironment and influences cancer initiation, promotion and treatment response. A growing awareness of the impact of the microbiome on tryptophan (Trp) metabolism in the context of carcinogenesis has prompted this review. We first compare the different metabolic pathways of Trp under normal cellular physiology to colon carcinogenesis, in both the host cells and the microbiome. Second, we review how the microbiome, specifically indoles, influence host tryptophan pathways under normal and oncogenic metabolism. We conclude by proposing several dietary, microbial and drug therapeutic modalities that can be utilized in combination to abrogate tumorigenesis.

A field experiment was conducted for 2 years in Green Tea Laboratory of Saitama Prefectural Agriculture and Forestry Research Center, Iruma, Saitama, Japan from March 2014 to December 2015. Controlled release fertilizers (CRF) or organic fertilizers (ORG) which is the mixture of chicken manure and oil cakewere applied with the amount of 450 kg N ha^-1 yr^-1 in 2014 and 397 kg N ha^-1 yr^-1 in 2015. Nitrous oxide (N₂O) emissionsfrom soil in green tea fields were measured by closed chamber method. The results showed that CRF has significantly lower N₂O compared to ORG. The cumulative N₂O emissions from CRF accounted for 51% of N₂O emissions from ORG fields and 138% of control with no fertilizer treatment. The N₂O flux from the row was higher than that of under the canopy, since fertilizer were applied on the row. However the total emission from the area between the rows was lower than that under the canopy because of the area ratio of row and canopy was 1:5.

It is an utmost importance to characterize drug candidates as early in the development pipeline as possible. Appropriate application of the emerging high throughput analytical techniques unlocks the opportunities to obtain experimental data for in vitro absorption, distribution, metabolism and elimination (ADME) profiling of large compound libraries which is crucial for selection of lead compounds. In an usual scenario, only one drug candidate will be selected from thousands of early compounds based on several stability and screening results. A high to medium throughput screening approaches could significantly accelerates the subsequent research and production phases. Traditionally, the analysis of metabolic stability assays heavily relies on high throughput LC-MS/MS techniques to meet with the lead profiling demands. In this study presented an innovative experimental approach that can offer a refreshing alternative. Laser Assisted Rapid Evaporative Ionization Mass Spectrometry (LA-REIMS) is a quick and efficient method for characterizing complex biological samples without laborious sample preparation and chemical separation. Therefore, using an automated LA-REIMS well plate reader as fast as 8 seconds per sample, we assessed the oxidative metabolic stability of active agents using biomimetic metalloporphyrin-based oxidative model reactions at various pH for commercially available drug substances and compared stability measurements with traditional HPLC-DAD-MS results.

The synthesis, anticancer and antioxidant activity of a series of indole-derived hybrid chalcones are reported here. First, using well known Claisen-Schmidt condensation method a set of 29 chalcones has been designed, synthesized, and consequently characterized. Subsequently, screening for the antiproliferative activity of the synthesized hybrid chalcones was performed on the on five cancer (HCT116, HeLa, Jurkat, MDA-MB-231 and MCF7) and two non-cancer (MCF-10A and Bj-5ta) cell lines. Chalcone 18c bearing 1-methoxyindole and catechol structural features, exhibited selective activity against cancer cell lines with IC50 values of 8.0 ± 1.4 µM (Jurkat) and 18.2 ± 2.9 µM (HCT116) and showed no toxicity to non-cancer cells. Furthermore, antioxidant activity was evaluated using tree different methods. The in vitro studies of radical scavenging activity utilizing DPPH radicals, as well as FRAP method, demonstrated the strong activity of catechol derivatives 18a-c. According to the ABTS radical scavenging assay, the 3-methoxy-4-hydroxy substituted chalcones 19a–c were slightly more favorable. In general, a series of 3,4-dihydroxychalcone derivatives showed properties as a lead compound for both antioxidant and anticancer activity.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

The 5-hydroxymethylfurfural (HMF) is a six-carbon heterocyclic organic compound with two substituents an aldehyde group and an alcohol group. It is formed from saccharides as a result of two reactions: the Maillard reaction and the caramelization of saccharides. It has both a negative and a positive effect on the human body, which makes it, even more, an attractive research object. The objective of the study was to determine HMF content in honey samples available on the Polish market using three varied methods and compare the results obtained. The methodology used included: two spectrophotometric methods (by White and Winkler) and the HMF determination method based on the LC-MS/MS technique developed uniquely for this study. The determined HMF content in all tested honey samples did not exceed the applicable standard. All results are within the scope of the European Council Directive 2001/110/EC of 20 December 2001, i.e. they do not exceed HMF content in honey, which is 40 mg/kg.

The COVID-19 pandemic has posed a significant threat to society in recent times, endangering human health, life, and economic well-being. The disease spreads quickly due to the highly infectious SARS-CoV-2 virus, which has undergone numerous mutations. Despite intense research efforts by the scientific community since its emergence in 2019, no effective therapeutics have been discovered yet. While some repurposed drugs have been used to control the global outbreak and save lives, none have proven universally effective, particularly for severely infected patients. Although the spread of the disease is generally under control, anti-SARS-CoV-2 agents are still needed to combat current and future infections. This study reviews some of the most promising repurposed drugs containing indolyl heterocycle, which is an essential scaffold of many alkaloids with diverse bio-properties in various biological fields. The study also discusses natural and synthetic indole-containing compounds with anti-SARS-CoV-2 properties, as well as computer-aided drug design (in-silico studies) for optimizing anti-SARS-CoV-2 hits/leads.

Introduction Atherosclerotic disease is a major contributor to heart failure, stroke, and myocardial infarction, significantly lowering the quality of life and life expectancy, with a significant burden on healthcare. Not all lesions deemed non-significant are benign, and conversely, not all significant lesions are causative of ischemia. Fractional flow reserve (FFR) provides a functional assessment of coronary lesions, while optical coherence tomography (OCT) offers detailed imaging of plaque morphology, aiding in therapeutic decision-making. The objective of this study was to evaluate the utility of OCT and FFR as adjunctive tools in the catheterization laboratory for guiding therapeutic decisions in patients with multivessel disease for non-culprit vessels. Specifically, we aimed to assess how OCT and FFR influence therapeutic decision-making in patients with multi-vessel coronary artery disease. Methods 36 patients with acute coronary syndrome (ACS) and multivessel disease were randomized 1:1 into two groups: one guided by FFR alone, and the other by a combination of FFR and OCT. For the FFR group, revascularization decisions for non culprit lesions were based solely on FFR measurements. If the FFR was >0.8, the procedure concluded, and the patient received maximal medical treatment. If the FFR was ≤0.8, a stent was placed. For the FFR + OCT group, if the FFR was >0.8, the revascularization decision was based on OCT findings. If there were no vulnerable plaques (VP), the procedure concluded, and the patient received maximal medical treatment. If OCT imaging indicated VP, then the patient underwent revascularization. If the FFR was ≤0.8, the patient underwent revascularization regardless of OCT findings. Results OCT imaging altered the therapeutic decision in 11 cases where FFR measurements were above 0.8, but the lesions were characterized as VP. Analyzing the total change in the decision to stent, 4 cases in the FFR group and 15 cases in the FFR and OCT group (4 based on FFR and 11 on OCT) revealed a statistically significant difference (p = 0.0006; Relative Risk = 0.2556; 95% CI: 0.1013 to 0.5603). When analyzing the change in the total decision both to stent and not to stent, we observed a statistically significant difference, with Group 1 having 7 cases and Group 2 having 15 cases (p = 0.0153; Relative Risk = 0.4050; 95% CI: 0.2004 to 0.7698) Conclusion Based on the findings of this study, OCT significantly increases the percentage of stenting procedures by identifying vulnerable lesions. The use of intracoronary imaging facilitates the timely identification and treatment of these vulnerable lesions. This underscores the crucial role of OCT in enhancing the precision of coronary interventions by ensuring timely intervention for vulnerable lesions, thereby potentially improving patient outcomes Acknowledgment funding „This work was supported by the University of Medicine, Pharmacy, Science and Technology ,, George Emil Palade’’ of Targu Mures Research Grant number 510/14/17.01.2022”

The presence of antibiotic residues in honey has recently become a growing public health concern due to the overuse of these products in beekeeping and their transfer to the food industry. The aim of this study was to develop and validate a simple, selective and sensitive method for the simultaneous identification and quantification of residues of twenty-two sulfonamides, trimethoprim and dapsone in honey using a rapid and reliable liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. The developed method showed good linearity, specificity, precision (repeatability and intra-laboratory reproducibility) and recovery. The decision limit (CCalpha) ranged between 2.16-22.12 µg/kg for CCα, while the detection capability (CCbeta) was between 2.16- 2.67-27.36 µg/kg. The method proved to be rapid, reliable and effective for the determination of sulfonamides, trimethoprim and dapsone from honey samples. The average recoveries were estimated to be between 70 and 106%. The relative standard deviations (RSDs) were between 6-18%. In practice, the method is essential to check the honey sold on the market and ensure its safety before it reaches the consumer.

Theoretical studies on the generation of nondiffracting and nondispersive light pulses and their experimental implementation are one of the renowned problems within electromagnetics. Current technologies enable creation of short-duration pulses of a few cycles with high power and fluency. An application of these techniques to the field of nondiffracting and nondispersive pulses requires a proper mathematical description of highly focused vector pulses. In this work, we study vector optical bullets in a dielectric medium with different polarization structures: linear, azimuthal, and radial. We report the differences caused by the vector model compared to the scalar model. We analyze effects caused by superluminal, subluminal, or even negative group velocity on properties of vector optical bullets inside a dielectric material.

The recent increase in global consumption of rice has led to increased demand for sustainable water management in paddy cultivation. In this study, we propose an enhanced paddy simulation module to be introduced to Soil and Water Assessment Tool (SWAT) to evaluate the sustainability of paddy cultivation. The enhancements added to SWAT include: (1) modification of water balance calculation for impounded fields, (2) addition of an irrigation management option for paddy fields that are characterized by flood irrigation with target water depth, and (3) addition of a puddling operation that influences the water quality and infiltration rate of the top soil layer. In a case study, the enhanced model, entitled SWAT-Paddy, was applied to an agricultural watershed in Japan. The results showed that the SWAT-Paddy successfully represented paddy cultivation, water management, and discharge processes. Simulated daily discharge rates with SWAT-Paddy (R² = 0.8) were superior to the SWAT result (R² = 0.002). SWAT-Paddy allows the simulation of paddy management processes realistically, and thus can enhance model accuracy in paddy-dominant agricultural watersheds.

Outbreaks of the crown-of-thorns seastar (CoTS) represent a major cause of coral loss on the Great Barrier Reef. Outbreaks might be explained by enhanced larval survival supported by higher phytoplankton availability after flood events, yet little is known about CoTS larvae feeding behaviour, in particular their potential for selective feeding. Here, single- and mixed-species feeding experiments were conducted on CoTS bipinnaria larvae using five algae (Phaeodactylum tricornutum, Pavlova lutheri, Tisochrysis lutea , Dunaliella sp. and Chaetoceros sp.) and two algal concentrations (1000 and 2500 algae mL^-1). Cell counts using flow-cytometry at the beginning and end of each incubation experiment allowed us to calculate the filtration and ingestion rates of each species by CoTS larvae. In line with previous studies, CoTS larvae ingested more algae when initial algal concentration was higher. We found evidence for the selective ingestion of some species (Chaetoceros sp., Dunaliella sp.) over others (P. lutheri, P. tricornutum). The preferred algal species had the highest energy content, suggesting that CoTS selectively ingested the most energetic algae. Ultimately, combining these results with spatio-temporal patterns in phytoplankton communities will help elucidate the role of larval feeding behaviour in determining the frequency and magnitude of CoTS outbreaks.

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.

Omega-3 polyunsaturated fatty acids (ɷ-3 PUFAs) offer diverse health benefits, such as supporting cardiovascular health, improving cognitive function, promoting joint and musculoskeletal health, and contributing to healthy aging. Despite their advantages, challenges like oxidation susceptibility, low bioavailability, and potential adverse effects at high doses persist. Nanoparticle encapsulation emerges as a promising avenue to address these limitations while preserving stability, enhanced bioavailability, and controlled release. This comprehensive review explores the therapeutic roles of omega-3 fatty acids, critically appraising their shortcomings and delving into modern encapsulation strategies. Furthermore, it explores the potential advantages of Metal-organic framework nanoparticles (MOF NPs) compared to other commonly utilized nanoparticles in improving the therapeutic effectiveness of omega-3 fatty acids within drug delivery systems (DDS). Additionally, it outlines future research directions to fully exploit the therapeutic benefits of these encapsulated omega-3 formulations for cardiovascular disease treatment.

We aimed to evaluate the protective effects of acetyl-xylogalactan on the activity of RAW264.7 macrophages against heat stress. To this end, we assessed cell survival, phagocytic activity, in-tracellular Ca2+ level, mitochondria potential exchange, apoptotic assay findings, galactosidase activity and the RNA-seq by NGS and real-time polymerase chain reaction (PCR) expression. In our evaluation of macrophage morphology at 37°C and 41°C, the macrophages showed an oval shape at 41°C , unlike the spindle shape at 37°C. Therefore, 41°C was chosen as the heat stress condition. Subsequently, we designed an experiment to evaluate changes in the RAW264.7 macrophages after acetyl-xylogalactan treatment under heat stress. The survival of RAW264.7 macrophages treated with acetyl-xylogalactan was higher than that of controls that were not treated with acetyl-xylogalactan. Moreover, on the basis of the results of the annexin-V detection assay, the apoptotic activity of macrophages appeared to have reduced after treatment with ac-etyl-xylogalactan. Moreover, treatment with acetyl-xylogalactan resulted in a stronger recovery trend in the intracellular Ca2+ and mitochondrial membrane potential after heat stress. RNA sequencing and real-time polymerase chain reaction (PCR) illustrated that Sarcodia suieae acetyl-xylogalactan could upregulate the expression of the anti-apoptosis Cflar gene and down-regulate the expression of the apoptosis factors Ddit3, and Hyou1 to protect macrophages under heat stress.

The cell case temperature versus time profiles of a multistage fast charging technique (4C-1C-CV)/fast discharge (4C) in a 2.3 Ah cylindrical lithium-ion cell are analyzed using a 1D thermal model. Heat generation is dominated by the irreversible component associated to cell overpotential, although evidences of the reversible component are also observed, associated to the heat related to entropy from the electrode reactions. The final charging stages (i.e., 1C-CV) significantly reduce heat generation and cell temperature during charge, resulting in a thermally safe charging protocol. Cell heat capacity was determined from cell specific heats and cell materials thickness. The 1D model adjustment of the experimental data during the 2 min. resting period between discharge and charge allowed us to calculate both the time constant of the relaxation process and the cell thermal resistance. The obtained values of these thermal parameters used in the proposed model are almost equal to those found in the literature for the same cell model, which suggests that the proposed model is suitable for its implementation in thermal management systems.

To elucidate mesenchymal stromal cells (MSC)-tumor intricate and ambiguous interactions, the reliable cell labeling and tracking techniques are imperative. Traditional methods of cell labelling have limitations mostly relevant to need for genetic modification what demands the exploration for alternative strategies. Here, we propose using fluorescent photoconvertible microcapsules containing Rhodamine B (RhB) to study mMSC migration in brain tumors. These 3 μm sized microcapsules are readily internalised by cells and undergo photoconversion under 561 nm laser exposure with fluorescence blue shift on demand. Optimal photoconversion was achieved with a laser irradiation duration of 0.4 ms, which provide a maximal brightness of photoconverted label without an excessive laser exposure on cells. Capsules modified with polyallylamine hydrochloride demonstrated the best potential for intracellular uptake without significantly affecting cell viability, motility, or proliferation. The optimal ratio of 20 capsules per mMSC was determined for labeling. Moreover, migration of individual mMSCs within 2D and 3D glioblastoma cell (EPNT-5) colonies over 2 days and in vivo tumor settings over 7 days was tracked. Our study unveils a robust platform for investigating MSC-tumor dynamics, offering insights into therapeutic strategies. Photoconvertible microcapsules could also become an indispensable tool for studying complex fundamental processes of cell-cell interactions for a wide range of problems in biology and medicine.

Terrestrial orchid tubers are an important source of food in some parts of Africa and are traditionally included in the diets of most rural communities in Malawi. However, there is limited information on the nutritional and phytochemical content of the Malawian orchids to substantiate their traditional use. The present study evaluates the nutritional and phytochemical variation of four orchid species: Disa zombica, Satyrium buchananii, Satyrium carsonii, and Satyrium trinerve, collected from the same ecological zone of Malawi. The proximate content, minerals, phytochemicals, and functional properties were analysed using official procedures. Protein ranged from 2.19% to 4.65%, whereas carbohydrate ranged from 65.24% to 80.22%, with S. carsonii and S. trinerve registering the highest protein and carbohydrate contents, respectively. Iron and potassium were highest in D. zombica, while sodium and calcium were highest in S. buchananii. The total phenolics ranged from 228.56 to 500.00 mg GAE/100 g, with D. zombica registering the highest. The water absorption capacity ranged from 4.10 to 10.88 g/g. Albeit variable levels, the study provides evidence that orchid species contain essential nutrients and phytochemicals important for human nutrition and health. Furthermore, the functional properties can be utilised in the development of food products, such as baked products.

Childhood obesity has become a global epidemic, with significant increases in prevalence over recent decades. While excessive calorie consumption and physical inactivity are known factors, emerging research highlights the role of Endocrine-Disrupting Chemicals (EDCs), particularly obesogens, in obesity's pathogenesis. This review explores the historical context of the environmental obesogens hypothesis, their sources, mechanism of action, impact on prenatal and postnatal development and epigenetics. Additionally, it discusses the long-term consequences of childhood obesity and proposes prevention strategies that will mitigate the negative health effects. Obesogens were found to disrupt hormonal balance and metabolic processes through various mechanisms such as altering gene expression, hormonal interference, and inflammation. Especially significant, was exposure during critical windows of development which correlates with increased risk of obesity in childhood or adolescence. Long-term effects of childhood obesity include chronic health conditions and psychosocial issues. A comprehensive approach is necessary to address childhood obesity, encompassing genetic, environmental, and lifestyle factors. Prevention strategies should focus on reducing obesogens exposure, promoting healthy lifestyles, and implementing regulatory policies. Future research should investigate obesogens-diet interactions, microbiome impacts, and combined obesogens effects. Long-term human studies are also crucial for validating findings from animal models and allow for inform decision-making to combat the obesity pandemic.

A mathematical procedure enabling the transformation of an arbitrary tessellation of a surface into a bi-colored complete graph is introduced. Polygons constituting the tessellation are represented by vertices of the graphs. Vertices of the graphs are connected by two kinds of links/edges, namely, by a green link, when polygons have the same number of sides, and by a red link, when the polygons have a different number of sides. This procedure gives rise to a semi-transitive, complete, bi-colored Ramsey graph. The Ramsey number was established as R_trans (3,3)=5. Shannon entropies of the tessellation and graphs are introduced. Ramsey graphs emerging from random Voronoi and Poisson Line tessellations were investigated. The limits ζ=lim┬(N→∞)⁡〖N_g/N_r 〗, where N is the total number of green and red seeds, N_g and N_r, were found ζ=0.272±0.001 (Voronoi) and ζ= 0.47±0.02 (Poisson Line). The Shannon Entropy for the random Voronoi tessellation was calculated as S= 1.690±0.001 and for the Poisson line tessellation as S =1.265±0.015.

This paper presents the work done to transition the lab scale synthesis (1 g) to a large scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol; a new pharmaceutical for treatment of antibiotic resistant Pseudomonas aeruginosa biofilm infections. The potentially hazardous diazotisation step in the lab scale synthesis was transformed to a safe and easy to handle flow chemistry step. Additionally, the paper presents an OSHA recommended safety assessment of the active compound E, performed by Fauske and Associates, LLC.

As a precious natural resource, forests are being destroyed. In previous studies, there is a lack of interactive assessment of its distribution that comprehensively considers multiple external disturbances. This paper takes the Barcelona Metropolitan Region as an example. Based on remote sensing, it analyzes the development process of the forest from 2006 to 2018 through multiple landscape indicators, and OLS models were established to analyze variables that have direct and indirect effects on forest distribution. In addition, the ecological structure of the forest was analyzed based on NDVI. It was found that the forest area is the largest but has been decreasing, becoming more complex in distribution structure. Much of the forest was converted to agricultural land and grassland. The green quality of forests was increasing, and the broad-leaved forest, the second largest area, contributes the most. NDVI is the most important positively correlated variable, and daytime surface temperature is an important inverse factor related to NDVI. In addition, NDBI is also a negative condition that inhibits forest development. In conclusion: The BMR forest area is decreasing and becoming more fragmented. NDVI and daytime LST are the two most significant factors. Climate warming may lead to worse forest development.

Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by an abnormal expansion of CAG repeats in the disease gene ATXN3, leading to prolonged polyglutamine (polyQ) tracts in the respective protein ataxin-3. The polyQ-expanded protein forms polyQ-containing aggregates in several brain regions which leads to neuronal cell loss. Autophagy is thought to play a significant role in clearing these polyQ-containing protein aggregates. Therefore, the autophagy mechanism was investigated in SCA3 with focus on the autophagic protein p62/sequestosome-1. Human and mouse RNA sequencing data were analyzed to determine RNA expression level of autophagic genes. Additionally, autophagy was studied in the SCA3 304Q knock-in mouse model and through several cell culture experiments using HEK-293T cells transfected with ATXN3 of differ-ent polyQ lengths. For cell culture experiments, autophagy was induced with rapamycin treat-ment, proteasomal degradation was blocked with MG132 and degradation of autophagic pro-teins was investigated using cycloheximide treatment. Here, we report an increased autophagy impairment with SCA3 disease progression seen in HEK-293T cells transfected with ATXN3 plasmid with expanded polyQ tracts, higher aged 304Q-knock-in mice, or human post-mortem brain material. Furthermore, co-localized aggregation of the autophagic protein p62 and the dis-ease protein ATXN3 was observed in the course of SCA3 disease. Therefore, we suggest a signifi-cant role for p62 in aggregate formation seen in the neurodegenerative disease SCA3.

The 2-Acetyl-1-pyrroline (2-AP) is the most important volatile in determining the aroma of fragrant rice, however, the transcriptional regulation mechanism of 2-AP biosynthesis in fragrant rice is still unclear. In this study, the Osp5cs1 knockout mutant lines and OsP5CS1 over-expression lines were constructed by genetic transformation of indica rice cultivar i.e., ‘Zhonghua11’, which was knocked out OsBADH2 to produce fragrance in aromatic rice. The OsP5CS1 gene was also identified as a key gene in the 2-AP biosynthesis pathway of aromatic rice. The OsP5CS1 promoter was used as bait, and the transcription factor OsbZIP60-like was screened by yeast one-hybrid assays. The transcription factor OsbZIP60-like specifically bound to the OsP5CS1 gene. The dual luciferase reporting system found that OsbZIP60-like transcription factor promoted the transcriptional activation of OsP5CS1. Compared with the wild type, the OsP5CS1 gene expression was significantly down-regulated in Osbzip60-like mutant, and resulted in substantial reduction in 2-AP biosynthesis. Moreover, the OsP5CS1 gene expression was significantly up-regulated in OsbZIP60-like over-expressed plants, and the 2-AP concentrations were also increased whereas the Osbzip60-like mutants were found to be sensitive to Zn deficiency. Overall, the OsbZIP60-like transcription factor promoted the 2-AP accumulation. This study provides a theoretical basis for the transcriptional regulation mechanism of 2-AP biosynthesis and explores the function of OsbZIP transcription factor in fragrant rice.

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

One of the important air pollutants is ammonia, which is mainly emitted from the agriculture sector. This sector is responsible for over 81% of global ammonia emissions. The main threat related to ammonia emissions is water eutrophication and soil acidification. The aim of the research was a preliminary assessment of the implementation status of methods for reducing ammonia emissions on farms and to learn the views and awareness of agricultural producers on reducing emissions of pollutants into the air. The research was conducted using a survey questionnaire that was made available to farmers in various ways. Based on the results of pilot surveys, it can be concluded that farmers have general knowledge of environmental protection and generally agree that people have an impact on the state of the environment. Low-emission practices to reduce ammonia emissions from agricultural sources are not widely used. The best situation is regarding reduction practices in the storage of natural fertilizers and the use of low-emission fertilizer application techniques. Some reduction activities are not obligatory, therefore it is difficult to determine the scope of application of these practices. Therefore, such periodic research will allow monitoring the activity of agricultural producers in implementing reduction methods.

Liver X receptors (LXR) are deemed as potential drug targets for atherosclerosis, whereas a role in adipose tissue expansion and its relation to insulin sensitivity remains unclear. To assess the metabolic effects of LXR activation, C57BL/6 mice on a high-fat diet (HFD) were treated with the dual LXRα/β agonist T0901317 (30 mg/kg per day) for 3 weeks. Differentiated 3T3-L1 was used for analysing the effect of T0901317 on glucose uptake.T0901317 reduced fat mass, accompanied by a massive fatty liver and lower adipokine levels in circulation of HFD mice. Increased adipocyte apoptosis and macrophage infiltration were found in epididymal fat of T0901317-treated HFD mice. In addition, T0901317 treatment promoted basal lipolysis, but blunted the anti-lipolytic action of insulin. Furthermore, LXR activation antagonized PPARγ target genes in epididymal fat and PPARγ-PPRE binding activity in 3T3-L1 adipocytes. Although the glucose tolerance was comparable to that in vehicle-treated HFD mice, the insulin tolerance was significantly decreased in T0901317-treated HFD mice, indicating decreased insulin sensitivity by T0901317 administration, and which was further supported by impaired insulin signalling found in epididymal fat and decreased insulin-induced glucose uptake in 3T3-L1 by T0901317administration. These findings reveal that LXR activation impairs adipose expansion which contributes to decreased insulin sensitivity.

The rationalization of single molecule magnets’ (SMMs) magnetic properties by quantum mechanical approaches represents a major task in the field of the Molecular Magnetism. The fundamental interpretative key of molecular magnetism is the phenomenological Spin Hamiltonian and the understanding of the role of its different terms by electronic structure calculations is expected to steer the rational design of new and more performing SMMs. This paper deals with the ab initio calculation of isotropic and anisotropic exchange contributions in the Fe(III) dimer [Fe₂(OCH₃)₂(dbm)₄]. This system represents the building block of one of the most studied Single Molecule Magnets ([Fe₄RC(CH₂O)₃)₂(dpm)₆] where R can be an aliphatic chain or a phenyl group just to name the most common functionalization groups) and its relatively reduced size allows the use of a high computational level of theory. Calculations were performed using CASSCF and NEVPT2 approaches on the X-ray geometry as assessment of the computational protocol, which has then be used to evinced the importance of the outer coordination shell nature through organic ligand modelization. Magneto-structural correlations as function of internal degrees of freedom for isotropic and anisotropic exchange contributions are also presented, outlining for the first time the extremely rapidly changing nature of the anisotropic exchange coupling.

Diastolic dysfunction, a prevalent condition characterized by impaired relaxation and filling of the left ventricle, significantly contributes to heart failure with preserved ejection fraction (HFpEF). Galectin-3, a β-galactoside-binding lectin, has garnered attention as a potential biomarker and mediator of fibrosis and inflammation in cardiovascular diseases. This comprehensive review investigates the impact of galectin-3 on diastolic dysfunction. We explore its molecular mechanisms, including its involvement in cellular signaling pathways and interaction with components of the extracellular matrix. Evidence from both animal models and clinical studies elucidates galectin-3's role in cardiac remodeling, inflammation, and fibrosis, shedding light on the underlying pathophysiology of diastolic dysfunction. Additionally, we examine the diagnostic and therapeutic implications of galectin-3 in diastolic dysfunction, emphasizing its potential as both a biomarker and a therapeutic target. This review underscores the significance of comprehending galectin-3's role in diastolic dysfunction and its promise in enhancing diagnosis and treatment approaches for HFpEF patients.

The collection of photo shoots during the systematic monitoring activities is useful to witness the ecological role of marine phanerogams as hosts for a rich variety of organisms in coastal and transitional waters. Cymodocea nodosa is present in the Taranto seas. In the Mar Piccolo, it reached high covers in short times, up to 100%, due to the bettering of the environmental conditions. The most recent observations showed that it offers welcoming towards several vertebrates and invertebrates, native and non-indigenous, as well as to micro and macroalgae. The NPPR funded activities will make these observations more robust and structural.

In the Vietnamese Mekong delta, soil quality and crop yield are steadily declining under rice monocultures with three crops per year. The objective of this study was to evaluate the medium-term effects of rotating rice with upland crops and adding organic amendments on rice yield and relate it to soil quality. A field trial with split-plot design including two factors and three replicates was carried out from 2017 to 2020, over the course of nine consecutive cropping seasons. Crop rotations and organic amendments were applied as main-plot and subplot factors, respectively. The rotations were: 1) rice–rice–rice (R–R–R), 2) soybean–rice–rice (So–R–R), and 3) sesame–rice–rice (Se–R–R), while organic amendment treatments included: i) no amendment (NO-AM); ii) compost of rice straw and cow manure (RS+CM), and iii) sugarcane compost (SGC); the composts were applied at a rate of 2.0 t ha-1. The rotation cycle started with the so-called spring–summer (SS), followed by summer–autumn (SA) and ended with the winter–spring (WS) season. Rice yield significantly (P < 0.05) increased by organic amendments after nine growing seasons (2019–2020 WS), with an increment of 5.1% for RS+CM (7.07 ton/ha) and 6.1% for SGC (7.14 ton/ha). Contrary to our expectation, rotations with upland crops did not significantly increase rice yield. Rice yield significantly and positively correlated with an integrated soil quality index SQI (r = 0.86) for the topsoil (0–15 cm), but not for the subsoil (15–30 cm). The increased availability of soil nutrients (Si and marginally also P) and improved soil physical properties probably induced by organic amendments, along with other soil properties under study, cumulatively attributed to enhanced rice yield. Use of a SQI involving several soil quality indicators enables to overall quantify the importance of soil fertility for rice yield versus other factors and it provides an effective means of quantifying the integrated effect of improved management. Moreover, integrating a wide range of soil quality indicators in a SQI ensures its applicability across diverse settings, including different crop rotations and various soil types.

Antioxidant, anti-inflammatory and chemo-preventive features have been reported for the carotenoid diatoxanthin. Diatoxanthin is only produced by a few groups of microalgae where it functions in photoprotection. Its large-scale production in microalgae is currently not feasible. In fact, rapid conversion into the inactive pigment diadinoxanthin is triggered when the cells are removed from the high-intensity light source, which will be the case during large-scale harvesting of microalgae biomass. Zeaxanthin epoxidase (ZEP) 2 and/or ZEP3 have been suggested to be responsible for the back-conversion of high-light accumulated diatoxanthin to diadinoxanthin in low light in diatoms. Using the CRISPR/Cas9 gene editing technology we knocked out the ZEP2 and ZEP3 genes in the already commercially used marine diatom Phaeodactylum tricornutum to investigate their role in the diadinoxanthin-diatoxanthin cycle, and to determine if one of the mutant strains could function as a diatoxanthin production line. Light shift experiments proved that ZEP3 encodes the enzyme converting diatoxanthin to diadinoxanthin in low light. Loss of ZEP3 caused the high-light accumulated diatoxanthin to be stable for several hours after the cultures had been returned to low light, suggesting that zep3 mutant strains could be suitable as commercial production lines of diatoxanthin.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Early detection and the modification of risk factors, such as diet, can reduce its incidence. Among food components the polyamines are important for maintaining gastrointestinal health and are metabolites of gut microbiota. Their disruption is linked to CRC, making polyamines a potential marker of the disease. This study analyzed the relationship between dietary components, including polyamines, and the presence of polyamines in feces to determine whether their presence could contribute to predicting the occurrence of colorectal lesions in patients. Fifty-nine participants of both sexes (aged 50 to 70 years) who had undergone colonoscopy screening for CRC (18 without and 41 with colorectal lesions) participate in the study. A nutritional survey and determination of fecal polyamine content were performed. Specific dietary components and putrescine levels were higher in patients with colorectal lesions. The diet ratio of putrescine/spermidine and the fecal content of N-acetyl putrescine and cadaverine were elevated in patients with precancerous lesions and adenocarcinomas, showing a potential predictive value for the presence of colorectal lesions. These findings suggest that N-acetyl putrescine and cadaverine could be complementary markers for the diagnosis of suspected colorectal lesions.

The safety concerns associated with current lithium-ion batteries are a significant drawback. A short-circuit within the battery's internal components, such as those caused by a car accident, can lead to ignition or even explosion. To address this issue, a polymer shear thickening electrolyte, free from flammable solvents, has been developed. It comprises a star-shaped oligomer derived from a trimethylolpropane (TMP) core and polyether chains, along with the inclusion of 20 wt.% nanosilica. Notably, the star-shaped oligomer serves a dual function as both the solvent for the lithium salt and the continuous phase of the shear thickening fluid. The obtained electrolytes exhibit an ionic conductivity of 10-6 S cm-1 at 20 °C and 10-4 S cm-1 at 80 °C, with a high Li+ transference number (t+ = 0.79). A nearly thirtyfold increase in viscosity to a value of 1187 Pa s at 25 °C and a critical shear rate of 2 s-1 were achieved. During impact, this electrolyte could enhance cell safety by preventing electrode short-circuiting.

The inclusion of various chemical substances in personal care products (PCPs) and cosmetic formulations can be associated with disruption and damage to the nervous system. Microplastics, benzophenones, parabens, phthalates and metals are among the most common chemical substances found in cosmetics that have been shown to induce neurotoxic mechanisms. Although cosmetic neurotoxin exposure is believed to be minimal, different exposure scenarios of cosmetics suggest that these neurotoxins remain a threat. Special attention should be paid to early exposure in the first gestation weeks, when critical processes, like the migration and proliferation of the neural crest derived cells start to form the ENS. Importantly, cosmetic’s neurotoxins can cross the placenta barrier and so affect the future embryo, but are also secreted in the breast milk, so that babies remain exposed for longer periods, even after birth. In this review we explore how neurotoxins contained in cosmetic and PCPs may have a role in the pathogenesis of various neurodevelopment disorders and neurodegenerative diseases, and therefore also in congenital enteric aganglionosis as well as in postnatal motility disorders. Understanding the mechanisms of these chemicals used in cosmetic formulations and their role in neurotoxicity is crucial to determining the safety of use for cosmetic products during pregnancy.

Indole derivatives are key components of natural products and possesses a wide range of biological and pharmaceutical applications. Here we present the synthesis of a new indole derivative namely 2-(1-ethyl-5-nitro-1H-indole-7-carbonyl) butyl 4-methylbenzenesulfonate (5). The structural elucidation of 5 was accomplished through comprehensive spectroscopic analysis, including Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS). Our molecular docking study revealed that compound 5 exhibits strong affinity towards Tyrosinase, making it a promising candidate as an antioxidant agent. Keywords: Indole derivative; Tosyl group; Molecular docking; Antioxidant agent.

Hirschsprung disease (HSCR, incidence 1/5000 live births) is caused by failure of neural crest-derived precursors to migrate, survive, proliferate or differentiate during the embryonic development of the Enteric Nervous System (ENS), which could be disrupted by many factors, in-cluding inflammatory processes. The NF-κB family controls several biological processes includ-ing inflammation, neurogenesis and cell migration. With the aim of studying the potential role of NF-κB in HSCR, we have analyzed the expression of the NF-κB main subunits and other NF-κB-related genes by RT-qPCR in HSCR tissue samples (sub-divided in ganglionic and agan-glionic segments). We found a decreased gene expression of the NF-κB main subunit RelA/p65, but also of IkBα, TNF-α, TFGBR2 and ERBB3 in the pathologic distal aganglionic segments com-pared to the proximal ganglionic segments. Moreover, we could also confirm the lower protein expression of RelA/p65 in the aganglionic distal segments by immunofluorescence staining. Fur-ther, we show that the expression of RelA/p65 in the proximal segments concurs with lymphocyte infiltration in the bowel tissue, indicating a pro-inflammatory activation of p65 in the proximal ganglionic HSCR tissue in the patients analyzed. In all, our findings suggest that the modulation of NF-κB signaling in the neuro-enteric system does obviously contribute to the pathological ef-fects in HSCR.

This paper, from the perspective of Mode 3 of knowledge production, takes the important carrier of knowledge, scientific research papers, as the research object. The mainstream databases (SCIE and SSCI) are chosen as the data sources. Firstly, bibliometric methods are applied to analyze the cooperation status among the main bodies of paper production, including authors and their affiliated institutions, countries, and disciplines; secondly, the Analytic Hierarchy Process (AHP) is used to construct a comprehensive evaluation model for the state of research cooperation in carbon neutrality. Based on the evaluation model, the cooperation characteristics of different disciplinary fields and the relationship between paper cooperation status and high-impact research papers are comparatively analyzed. At the same time, an analysis is conducted on the support from the government, the sponsorship from enterprises, and the participation of the public in the process of paper production. Finally, some suggestions are put forward on how to build an innovative ecosystem for carbon neutrality research from the perspective of Mode 3 of knowledge production.

The Speer allergic tension-fatigue syndrome (SATFS) is a classic syndrome characterized by allergy-like symptoms, muscle tension, headache, chronic fatigue, and a particular behavior. The particular behavior displayed includes symptoms such as hyperkinesis, hyperesthesia (i.e., insomnia), restlessness, and distractibility, among others. Interestingly, these symptoms are very similar to recent descriptions of attention deficit hyperactivity disorder (ADHD), the most prevalent neurodevelopmental disorder worldwide, which is characterized by inattention, hyperactivity and impulsivity. Although the exact cause of ADHD remains unknown, it has been proposed that deficiency of the enzyme diamine oxidase (DAO), which metabolizes histamine, may be involved in the development of ADHD. Our conceptual paper suggests that DAO enzyme deficiency may be involved in the development and severity of ADHD. Histamine, which is metabolized by DAO, plays an important role in the regulation of attention, memory and cognition. Therefore, decreased DAO activity could lead to an accumulation of histamine, which could contribute to ADHD symptoms. This study provides a theoretical framework for the relationship between DAO deficiency and ADHD, which could have important implications for the diagnosis and treatment of the disorder. Further empirical studies are needed to confirm our hypothesis and explore the clinical implications of the relationship between DAO deficiency, histamine, and ADHD.

The studied solar pot is a recent invention, which gained a utility model protection in 2021 from the Hungarian Intellectual Property Office under patent number 5489. The device is made for environmentally friendly cooking or heating (by utilizing solar energy) of foods and liquids. Its structure is similar to a double pipe heat exchanger, it has an outer mantle and an inner cooking tank. The goals of the paper are proposing a new physically-based mathematical model describing the solar pot and carrying out computer experiments with it, assembling an experimental system of the pot connected with a solar collector and performing measurements on it. Based on the results, the solar pot can successfully be used for cooking or sterilizing foods or liquids during the studied time period, in Hungary.

In this work, two plasmonic structures with two different periodic nanostructures (nanodisk and nanostrip arrays) separated from the gold layer by an ultrathin dielectric Al2O3 layer are proposed, and their optical properties are simulated as 3-dimensional models using COMSOL Multiphysics software tool. The optical responses, such as the amplification of the electric field and the scattering, absorption and extinction cross sections of the two structures, are investigated and compared. The results show that both structures show strong field enhancement in their gap layer, and the structure with the periodic array of metal nanodisks shows stronger field enhancement and larger absorption, extinction, and scattering cross sections in its dipole resonance wavelength, which is defined as a bright plasmonic mode. In addition, some weaker resonant modes are observed for both structures and the reason for their generation is dis-cussed. The analysis of different possible modes in such structures is crucial for their application in various fields.

Nowadays, animal breeders look for effective innovations to care animal health. Use of probiotics, postbiotics, parabiotics and the other beneficial natural substances are dominated. Mundticin-like substance EM 41/3 is thermo-stable bacteriocin (postbiotic) with a broad antimicrobial spectrum. In this study its effect in broiler rabbits was assessed. Rabbits represent food-derived animal and they are also suitable animal model. The parameters tested were analyzed by validated methods. Administration of MLS EM 41/3 produced by non-autochthonous strain Enterococcus mundtii EM 41/3 lead to significant increase of parameter immunity-phagocytic activity, while it did not influence microbiota composition. It also did not influence blood biochemistry and no oxidative stress was noted. Moreover, higher growth parameters were noted and also stimulated hydrolytic activity. Finally, no negative influence on rabbit meat quality was noted. Postbiotic MLS EM 41/3 administration in feeding strategy seems to be contributing fact for rabbit health status maintaining.

Mapping short-term wetland vegetation and water storage changes is valuable for monitoring the biogeochemical processes of wetland systems. Old Woman Creek National Estuarine Research Reserve is a dynamic freshwater estuary that experiences intermittent changes in water level over the course of a year. Small unmanned aerial systems (sUAS) are useful tools in monitoring changes as they are rapidly deployed, repeatable, and high-resolution. In this study, commercial quadcopters were paired with a red/green/near-infrared MAPIR Survey 3W camera to produce normalized difference vegetation index (NDVI) and normalized difference water index (NDWI) maps to observe short-term changes at OWC. Orthomosaics were produced for flights on 8 days throughout 2018 and early 2019. The orthomosaics were calibrated to bottom-of-atmosphere reflectance using the Empirical Line Correction method and NDVI and NDWI maps were created. The NDVI pixel values were used to generate maps of vegetation extent showing density changes over time. Identifying dominant vegetation in these maps allowed for the application of the National Estuarine Reserve System (NERRS) Classification Codes to zones of interest. NDWI provided water extent at different water levels and when paired with LiDAR and bathymetric data yielded water volume and residence time estimates. The produced maps contribute to the overall understanding of habitats affected by water inundation variations.

Levels of trace element pollution in surface soil can be estimated using soil analyses and leaching tests. These methods may reveal different results due to the effect of soil properties, such as grain size and mineral composition, on elemental availability. Therefore, this study advocates an alternative method for monitoring and assessment of trace element pollution in surface soil using terricolous fruticose lichens. Lichens growing at abandoned mine sites and unpolluted areas in southwest Japan and their substrata were analyzed using inductively coupled plasma-mass spectrometry and X-ray fluorescence spectrometry to clarify the relationships between Cu, Zn, As, and Pb concentrations in lichens and soils, including their absorption properties. Concentrations of these elements in the lichens were positively correlated with those in the soils regardless of lichen species, location, habitat, or conditions of soils. The analyzed lichens had neither competitive nor antagonistic properties in their elemental absorption, which made them good biomonitors of trace element pollution in surface soil. The distribution maps of average Cu, Zn, As, and Pb concentrations at each sampling region detected almost all of the Cu, Zn, and As pollution of the soils. Therefore, lichens could be used in practical applications to monitor Cu, Zn, and As pollution in surface soils.

Genetic testing allows for identification of germline DNA variations which are associated with a significant increase in risk of developing breast and ovarian cancer. Detection of a BRCA1 or BRCA2 pathogenic variant triggers several clinical management actions, which may include increased surveillance and prophylactic surgery for healthy carriers or treatment with PARP inhibitor therapy for carriers diagnosed with cancer. Thus, standardized validated criteria for annotation of BRCA1 and BRCA2 variants according to their pathogenicity are necessary to support clinical decision making and ensure improved outcomes. Upon detection, variants whose pathogenicity can be inferred by the genetic code are typically classified as pathogenic, likely pathogenic, likely benign, or benign. Variants whose impact on function cannot be directly inferred by the genetic code are labeled as Variants of Uncertain Clinical Significance (VUS) and are evaluated by multifactorial likelihood models that use personal and family history of cancer, segregation data, prediction tools, and co-occurrence with a pathogenic BRCA variant. Missense variants, coding alterations that replace a single amino acid residue with another, are a class of variants for which determination of clinical relevance is particularly challenging. Here, we discuss current issues in variant classification by following a typical life cycle of a BRCA1 missense variant through detection, annotation and information dissemination. Advances in massively parallel sequencing have led to a substantial increase in VUS findings. Although comprehensive assessment and classification of missense variants according to their pathogenicity remains the bottle neck, new developments in functional analysis, high throughput assays, data sharing, and statistical models are rapidly changing this scenario.

On February 28th, 2023, Spanish Royal Decree 150/2023 as published, approving the plans for the management of the maritime space of the five Spanish marine demarcations. This Royal Decree Law inaugurates the Planning of the Maritime Space in Spain. Terrestrial Space Planning is very advanced, both in the legislation and in the instruments that are enabled to organize this space, from the national scale to the municipal scale, passing through the regional, provincial, and supra-municipal scales. Naturally, both Planning must converge and thus speak of an Integrated Space Planning. In some of the countries that we can take as global references, this convergence in the form of integration is taking place. On the other hand, and within the context of climate change, coastal cities will be the most affected, both by the potential rise in sea level and by the increasingly continuous and greater extreme events. Integrated Space Planning is postulated as the most effective tool to carry out adequate territorial and urban planning of our coastal cities, as well as to analyse the influence and possible corrective measures to apply against the effects produced by climate change.

Background: During the stay in the neonatal intensive care unit, parents play a crucial role in the care of their infants. Recent studies reported a decrease in parental participation due to Coronavirus Disease (COVID-19) pandemic that determined restricted access policies in hospitals. The aim of this study is to describe the barriers to a good parents’ participation during the stay in the neonatal intensive care unit in the COVID-19 era. Methods: A quantitative observational study was carried out. Results: 270 parents participated in this study. Mothers’ participation in care seems to be higher as compared to fathers (p = 0.017). Parents who lived the birth of their first child reported a better level of participation in care when compared to those who lived the birth of their second born (p = 0.005). Parents of extremely preterm neonates reported a lower interaction with their infant if compared to parents of term newborns (p < 0.001). Conclusions: Some more disadvantaged categories have reported lower scores: cultural and linguistic minorities, parents of multiple children and fathers. COVID-19 pandemic made several Family Centred Care activities not possible with a higher impact on those who benefited the most of these facilities. This study was prospectively registered by the IRB-CRRM of the University “G. d’Annunzio” Chieti-Pescara on the 23/01/2024 with registration number CRRM;2023_12_07_01.

Zwitterionic polymers emerge as very useful materials for applications in antifouling surfaces. The properties of these polymers can be tuned by variation of the chemical structure of the corresponding monomer. In this study, two zwitterionic ammonium sulfonate monomers bearing an hydroxyl function and a styrenic polymerizable groups were prepared in two steps. The two monomers were obtained using 4-vinylbenzyl chloride as the key precursor. The zwitterionic monomers were characterized by 1H NMR, 13C NMR, IR spectroscopy and high-resolution mass spectrometry (HRMS). These two monomers enable the preparation of novel zwitterionic polymers with enhanced hydrophilicity due to the presence of a hydroxyl group.

Hybrid reinforcement in a composite material (CM), in many situations, allows better govern material mechanical properties. Polymer matrix CM plate is reinforced with small particles and macro-fibers. Particles are oil shale ash (OSA) powder, macro-fibers – basalt fiber threads im-pregnated by matrix material. With the goal to find out elastic properties of the matrix- polymer with OSA, samples with its different concentrations were experimentally fabricated and their elastic properties were experimentally measured. Obtained data were used in numerical model-ling. Was observed polymer matrix composite slab, reinforced with OSA and three-dimensional (3D) basalt fiber fabric. Fabric are forming threads impregnated by matrix (polymer resin mixed with OSA particles). Damage accumulation in the stretched slab was modelled. Impregnated thread, in the modelling, is observed as a macro-fiber (MF) with averaged elastic properties. With the load increase MF in the material began to break. At first, appeared isolated single breaks. A probabilistic sequential MF rupture accumulation model was accepted and numerical-ly realized. The geometry of the reinforcing knitted fabric was modeled using the Leaf and Glaskin approach. In the knitted fabric highly, stressed MF cross-sections are observed as po-tential location where thread breakage can occur. If one thread breaks, the cross-sections of the adjacent threads experience the overload caused by this rupture. More overloaded crossection in the adjacent overloaded thread breaks and we obtain two adjacent broken MF designated as a defect with the size j=2. The probabilities of obtaining defect consisting of at least 2, 3, … j adjacent broken MF in the plate were calculated. The calculations continued until the rupture process becomes unstable (j→∞). The overstresses on adjacent threads in the CM were calculat-ed using the FEM three-dimensional numerical approach. Analytical and stochastic methods were used for the load-carrying capacity determination and different size defects accumulation in the hybrid composite material (HCM) plate. Also, was calculated the probability of the plate rupture.

Herein we present the biocatalysed preparation of mono-N-carbamate-protected precursor of antitumoral Nutlin-3a, through enantioselective alkoxycarbonylation of meso-1,2-disubstituted-1,2-diaminoethane, using enzyme lipases and dialkyl carbonates as acylating agents. A series of supported or free lipase enzymes were screened in combination with commercially available diallyl-, diethyl and dimethyl- carbonate. The reactions were conducted at different temperatures, reaction times and with variable co-solvent systems to evaluate the effect on the enzyme catalytic activity. The best results in terms of conversion, enantiomeric excess and yield were obtained when lipase from Candida antarctica B (CAL-B) was used with diallyl carbonate (DAC) conducting the reaction solventless at 75 °C.

Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3% and, more pronouncedly, of 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA.

We investigated the sleep-wake rhythm of nursery school children with the aim of supporting their health and balanced mental/physical development. We analyzed 4881 children from infant to 6 years of age, using 2-week sleep tables recorded by their guardians. The table contains sleep onset times, wake times, nighttime/daytime sleep duration, and the differences in these between weekdays and weekends. The total sleep decrement of children with age is due to a decrease in daytime sleep only, and nighttime sleep duration remains almost unchanged at about 10 hours, and is therefore called the nighttime basic sleep duration (NBSD). While sleep onset time stabilizes at around 9:30 pm by the age of 2, wake-up times to be before 7 am, resulted in weekdays sleep insufficiency. This lack of sleep is compensated by long naps on weekdays and by catching up sleep on weekends morning, which may be the background to future social-jet-lag. Guardians are encouraged to know their children's exact NBSD and set an ap-propriate bedtime to maintain it on weekdays, which prevent sleep dept and form a daily rhythm of waking up at the same time both on weekdays/weekends. These conditions are believed to maintain balance in mental/physical development and school-social-adaptation.

The optimal timing for actively discontinuing immune checkpoint inhibitor therapy in long-term responders with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains unresolved. We conducted a retrospective study of 246 patients with R/M HNSCC treated with nivolumab to determine the optimal timing to actively discontinue nivolumab therapy. We examined the point at which progression-free survival (PFS) plateaued in all cases. We compared the prognosis of 19 (7.7%) ongoing cases and 227 (92.3%) discontinued cases and analyzed treatment duration and treatment-free interval (TFI). The 6-year overall survival was 11.8% (median, 12.1), and the 6-year PFS was 15.3% (median, 3.0). The PFS curve remained stable for 3 years. The median duration of nivolumab treatment was 2.9 months (range, 0.03–81.9): Ongoing group, 41.8 (5.6–81.9); Decision group, 36.8 (4.0–70.1); Toxicity group, 30.6 (2.8–64.8); and progressive disease group, 2.0 (0.03–42.9). TFI in the Decision group was 15.1 months (0.6–61.6) and 30.6 months (2.8–64.8) in the Toxicity group. Limited number of long-term responders in R/M HNSCC cases treated with nivolumab exists. Given that PFS plateaued at 3 years, we propose that the optimal duration of treatment for this subset of patients is 3 years.

The concept of {\it quantum ratio} emerged in the recent efforts to understand how Newton's equations appear for the center of mass (CM) of an isolated macroscopic body at finite body-temperatures, as the first approximation to quantum-mechanical equations. It is defined as $Q\equiv R_q/L_0$, where the quantum fluctuation range $R_q$ is the spatial extension of the pure-state CM wave function, whereas $L_0$ stands for the body's linear size (the space support of the internal, bound-state wave function). The two cases $R_q /L_0 \lesssim 1$ or $R_q/ L_0 \gg 1$, roughly correspond to the body's CM behaving classically or quantum mechanically, respectively. In the present note we elaborate more on this concept, illustrating it in several examples. An important notion following from introduction of the quantum ratio is that the elementary particles (thus the electron and the photon) are quantum mechanical, even when the environment-induced decoherence turns them into a mixed state. Decoherence and classical state should not be identified. This simple observation, further illustrationed by the consideration of a few atomic or molecular processes, may have significant implications on the way quantum mechanics works in biological systems.

Rationale: The 14-3-3 protein family is known to interact with many proteins in non-cardiac cell types to regulate multiple signaling pathways, particularly those relating to energy and protein homeostasis; and the 14-3-3 network is a therapeutic target of critical metabolic and proteostatic signaling in cancer and neurological diseases. Although the heart is critically sensitive to nutrient and energy alterations, and multiple signaling pathways coordinate to maintain the cardiac cell homeostasis, neither the structure of cardiac 14-3-3 protein interactome, nor potential functional roles of 14-3-3 protein-protein interactions (PPIs) in heart has been explored. Objective: To establish the comprehensive landscape and characterize the functional role of cardiac 14-3-3 PPIs. Methods and Results: We evaluated both RNA expression and protein abundance of 14-3-3 isoforms in mouse heart, followed by co-immunoprecipitation of 14-3-3 proteins and mass spectrometry in left ventricle. We identified 52 proteins comprising the cardiac 14-3-3 interactome. Multiple bioinformatic analyses indicated that more than half of the proteins bound to 14-3-3 are related to mitochondria; and the deduced functions of the mitochondrial 14-3-3 network are to regulate cardiac ATP production via interactions with mitochondrial inner membrane proteins, especially those in mitochondrial complex I. Binding to ribosomal proteins, 14-3-3 proteins likely coordinate protein synthesis and protein quality control. Localizations of 14-3-3 proteins to mitochondria and ribosome were validated via immunofluorescence assays. The deduced function of cardiac 14-3-3 PPIs is to regulate cardiac metabolic homeostasis and proteostasis. Conclusions: Thus, the cardiac 14-3-3 interactome may be a potential therapeutic target in cardiovascular metabolic and proteostatic disease states, as it already is in cancer therapy.

Understanding and improving seismic resilience in regions prone to earthquakes is crucial for mitigating the effects of natural disasters. This study zeroes in on Montenegro, a region frequently affected by seismic activity, with the goals of critically evaluating current resilience levels, pinpointing key preparedness gaps, and assessing the efficacy of existing response strategies. Employing qualitative methods, the research involved semi-structured interviews with residents from Montenegro's most vulnerable areas, including Nikšić, Podgorica, Bar, Kotor, Cetinje, Budva, Herceg Novi, and Berane. These participants, selected for their firsthand experiences with significant earthquake impacts, contributed to a deeper understanding through discussions that aligned with a broad conceptual framework, exploring everything from the nuances of citi-zen resilience to local government responses and personal preparedness. The study aimed to gather in-depth views on community resilience during earthquakes, evaluate citizens' knowledge and preparedness for such disasters, and examine local governance strategies for enhancing seismic resilience. It revealed varying resilience levels across communities, with some displaying well-structured strategies while others showed notable deficiencies. The findings underscore the urgent need for community-specific preparedness programs and improvements in both structural and educational frameworks to enhance resilience. This research highlights the necessity of a comprehensive approach that includes detailed risk assessments, tailored preparedness training, and stronger public awareness efforts. Additionally, it emphasizes strengthening local governments' capabilities to enact and sustain effective response measures to ensure ongoing community resilience against future seismic challenges.

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.

We report neutralization titer data against contemporary SARS-CoV-2 sublineages from an ongoing, open-label, phase 2/3 trial of a single 30-μg dose of monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine. Healthy participants had previously received ≥3 doses of a US-authorized mRNA vaccine, with the most recent being a bivalent Omicron BA.4/BA.5-adapted vaccine administered ≥150 days before study vaccination. In this analysis, Omicron XBB.1.5, BA.2.86, and JN.1 serum neutralizing titers were assessed at baseline and 1 month after vaccination in a subset of ≥18-year-olds (N = 40) with evidence of previous SARS-CoV-2 infection. Immunogenicity was also evaluated in a demographically matched group of participants who received bivalent BA.4/BA.5-adapted BNT162b2 in another study (ClinicalTrials.gov Identifier: NCT05472038). The XBB.1.5-adapted BNT162b2 vaccine elicited higher XBB.1.5, BA.2.86, and JN.1 neutralizing titers than those elicited by bivalent BA.4/BA.5-adapted BNT162b2. Overall geometric mean fold rises in neutralizing titers from baseline to 1 month after vaccination were higher among participants who received XBB.1.5-adapted BNT162b2 than those who received bivalent BA.4/BA.5-adapted BNT162b2 for XBB.1.5 (7.6 vs 5.6), slightly higher for JN.1 (3.9 vs 3.5), and similar for BA.2.86 (4.8 vs 4.9). ClinicalTrials.gov Identifier: NCT05997290.

Rapid analysis and characterization of compounds by mass spectrometry may overlook trace compounds, although targeted analysis methods can significantly improve detection sensitivity, it is difficult to discover novel scaffold compounds. This study developed a strategy for discovering trace compounds in the aging process of traditional Chinese medicine based on MS fragmentation and known metabolic pathway. Specifically, we found that the characteristic component of C. reticulata 'Chachi', methyl N-methylanthranilate (MMA), fragmented in ESI-CID to produce rearrangement ion 3-hydroxyindole, which has been proven to exist in trace amounts in C. reticulata 'Chachi' comparing with the reference substance by LC-MS/MS. By combining the known metabolic pathways of 3-hydroxyindole and the possible methylation reactions that may occur during aging, 10 possible indole derivatives were untargeted predicted. These compounds were confirmed to originate from MMA by purchasing or synthesizing reference substances and all of them were detected in C. reticulata 'Chachi' through LC-MS/MS analysis, achieving trace compound analysis from untargeted to targeted. It may contribute to explain the aging mechanism of C. reticulata 'Chachi' and the strategy of CID-induced special rearrangement ion binding metabolic pathway has potential application value in discovering trace compounds.

Human number understanding is thought to rely on the analogue number system (ANS), working according to Weber’s law. We propose an alternative account, suggesting that symbolic mathematical knowledge is based on a discrete semantic system (DSS), a representation that stores values in a semantic network, similar to the mental lexicon or to a conceptual network. Here, focusing on the phenomena of numerical distance and size effects in comparison tasks, first we discuss how a DSS model could explain these numerical effects. Second, we demonstrate that DSS model can give quantitatively as appropriate a description of the effects as the ANS model. Finally, we show that symbolic numerical size effect is mainly influenced by the frequency of the symbols, and not by the ratios of their values. This last result suggests that numerical distance and size effects cannot be caused by the ANS, while the DSS model might be the alternative approach that can explain the frequency-based size effect.

Stroke constitutes a significant public health concern due to its impact on mortality and morbidity. This study investigates the utility of machine learning algorithms in predicting stroke and identifying key risk factors using data from the Suita study, comprising 7,389 participants and 53 variables. Initially, unsupervised K-prototype clustering categorized participants into risk clusters, while five supervised models including Logistic Regression (LR), Random Forest (RF), Support Vector Machine (SVM), eXtreme Gradient Boosting (XGBoost), and Light Gradient Boosted Machine (Light-GBM) were employed to predict stroke outcomes. Stroke incidence disparities among identified risk clusters using the unsupervised K-prototype clustering method are substantial, according to the findings. Supervised learning, particularly RF was a preferable option because of the higher levels of performance metrics. The Shapley Additive Explanations (SHAP) method identified age, systolic blood pressure, hypertension, estimated glomerular filtration rate, metabolic syndrome, and blood glucose level as key predictors of stroke, aligning with findings from the unsupervised clustering approach in high-risk groups. Additionally, previously unidentified risk factors such as elbow joint thickness, fructosamine, hemoglobin, and calcium level demonstrate potential for stroke prediction. In conclusion, machine learning facilitated accurate stroke risk predictions and highlighted potential biomarkers, offering a data-driven framework for risk assessment and biomarker discovery.

Magnetic resonance (MR) image acquisitions are usually time-consuming, limiting utilization in neuroimaging. For multiple sclerosis (MS) patients, MR imaging plays a major role in drug therapy decision-making. The purpose of this study was to evaluate whether an ultrafast, T2-weighted (T2w), deep-learning-enhanced (DL), echo-planar-imaging-based (EPI) fluid-attenuated inversion recovery (FLAIR) sequence (FLAIRUF) that has been targeting neurological emergencies so far might even be an option to detect MS lesions of the brain compared to conventional FLAIR sequences. Therefore, 17 MS patients were enrolled prospectively in this exploratory study. Standard MR protocols and ultrafast acquisitions were conducted at 3 tesla (T), including three-dimensional (3D)-FLAIR, turbo/fast spin echo (TSE)-FLAIR, and FLAIRUF. Inflammatory lesions were grouped by size and location. Lesion conspicuity and image quality were rated on an ordinal five-point Likert scale, and lesion detection rates were calculated. Statistical analyses were performed to compare results. Altogether, 568 different lesions were found. Data indicated no significant differences in lesion detection (sensitivity and positive predictive value [PPV]) between FLAIRUF and axially reconstructed 3D-FLAIR (lesion size ≥ 3 mm × ≥ 2 mm) and no differences in sensitivity between FLAIRUF and TSE-FLAIR (lesion size ≥ 3 mm total). Lesion conspicuity in FLAIRUF was similar in all brain regions except for superior conspicuity in the occipital lobe and inferior conspicuity in central brain regions. Further findings include location-dependent limitations of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as artifacts such as spatial distortions in FLAIRUF. In conclusion, FLAIRUF could potentially be an expedient alternative to conventional methods for brain imaging in MS patients since the acquisition can be performed in a fraction of time while maintaining good image quality.

This research aims to deepen the understanding of the relationship between conductivity and morphology in polypyrrole (PPy) via a comparison of the bipolaron to polaron ratios with a focus on the C-H deformation area. PPy samples were synthesized with different surfactants: sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and tween 80 (TW). The study revealed that SDS significantly altered the bipolaron and polaron in C-H deformation region and showed higher conductivity than other surfactants. Notably, the morphological shifts to a sheet-like structure when using ammonium sulfate (APS) contrasted with the particle-like form observed with ferric chloride (FeCl3). These results showed that if the oxidant changed, the bi-polaron and polaron ratios in C-H deformation were unrelated to PPy morphology. However, this work showed a consistent relationship between SDS use, the bipolaron and polaron ratios in the C-H deformation, and the conductivity properties. Moreover, the natural positive charge of PPy and negatively charged SDS molecules may lead to an electrostatic interaction between PPy and SDS. This work assumes that this interaction might cause the transformation of polaron to bipolaron in the C-H deformation region, resulting in improved conductivity of PPy. This work offers more support for the future investigation of PPy characteristics.

Plant-derived compounds have been historically used for the treatment of various diseases and an important source of several clinically useful anti-cancer agents. The Artemisia annua is known as a medicinal herb that is effective against cancer. Thus, the purpose of this study was to investigate whether ethanol extracts of Artemisia annua could increase an anti-cancer effect against LS174T cells. Our results show that Artemisia annua extracts (AAE) induces apoptosis through the regulation of mitochondria outer membrane potential. We demonstrate that apoptosis is induced by p53-dependent manner when cells were treated with Nutlin-3 (MDM2 inhibitor) and LY294002 (Akt inhibitor). In addition, the apoptotic effect was also observed in the p53-independent manner through pifithrin-α (p53 inhibitor) and celecoxib (COX-2 inhibitor) treatment. As in in vitro, AAE induced apoptotic effects and regulated apoptosis-related proteins in LS174T xenograft model. Taken together, these results suggest that Artemisia annua extracts exerts an anti-cancer effect through p53-independent manner, as well as p53-dependent manner by p53´ translocation in LS174T colon cancer cells.

Acetyleugenol is a phytochemical compound with broad effect against infectious diseases and tumors. Here, we extracted, characterized and elucidated the structure of acetyeugenol, for the first time, from the leaves of Acacia nilotica (L.)―a well-known medicinal plant. The broad antibacterial potential of acetyleugenol was first confirmed against seven bacterial pathogenic isolates with best activity against Proteus sp., Salmonella typhi, Staphylococcu aureus, and Streptococcus pneumonia, which showed similar or better zone of inhibition to that of the control amoxicillin. To further investigate its effect against Mycobacterium tuberculosis, acetyleugenol and its indole and phenyl analogs were subjected to molecular docking experiments against two potential tuberculosis drug targets―MtPknE and MtPknB Ser/Thr protein kinases. The results reveal that all of the analogs have improved docking scores comparing to the acetyleugenol. The indole analogs EUG-1 and EUG-3 were more effective with better docking scores for MtPknE with –11.08 and –10.05 kcal/mol, respectively. Similar results were obtained for the MtPknB. In contrast, only the EUG-2 phenyl analog has given rise to similar docking scores for both targets. This opens the door for further comprehensive studies on these acetyleugenol analogs with in vitro and in vivo experiments to validate and get more insights into their mechanisms of action.

To secure logic circuits against the illegal copying the insertion of the so-called key bit inputs using XOR/XNOR gates has been proposed in . The inserted gates modify (lock) the behavior of the original circuit and only the correct choice of the secret key bits guarantees the equivalent behaviour of the locked circuit to the original circuit. To break this kind of security, i.e. to find the secret key bits, there was a SAT solver based attack proposed in . The aim of this work is to experimentally verify this attack on several locked circuits with various number of primary inputs and outputs and with various number of gates. Except for the random placement of the key gates we evaluate also the positioning with chaining elimination. The obtained and presented results show that we were able to unlock 10 of 11 circuits within few minutes on a common PC.

From grape cultivation to ripening and harvest timing to processing, each step can be a critical point when it comes to wine quality and phenolic composition. In this study, the influence of winemaking technology on resveratrol and quercetin content, as well as other polyphenolic compounds, was investigated. Resveratrol is a non-flavonoid polyphenolic stilbene synthesized by grape skin when damaged by infectious diseases or ionizing radiation. Quercetin is a phenol found in grape skins and stems and is produced to protect grapes from UV light damage. Trans-resveratrol and quercetin are known to act as antioxidants, reduce the risk of atherosclerosis and type 2 diabetes, inhibit the growth of cancer cells, and prevent the release of allergic and inflammatory molecules. However, the question was whether red wine could be enriched with these phenols using an innovative winemaking technology. The innovative idea was to completely replace the cold maceration process with maceration with the addition of wild yeast (Torulaspora delbrueckii, Td). Maceration with the addition of wild yeast (Td) offers the following advantages over traditional cold maceration: (1) higher concentrations of trans-resveratrol (>35-40%) and quercetin (>35-40%) in the final wine, (2) the new wine has a higher potential for human health, (3) the wine has a better aroma and stability due to the higher mannoprotein content, and (4) the better energy efficiency in the production process. The study of stability during storage and aging also included derivatives of benzoic acid and hydroxycinnamic acid, piceid, catechin, naringenin, rutin, kaempherol, hesperetin, and anthocyanins. The study found that younger wines had higher phenolic content, while storage of the wine resulted in a decrease in total phenolic content, especially monomeric stilbenes and quercetin.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

Causative agent of the viral pneumonia outbreak in the World identified as SARS-CoV2 leads to a severe respiratory illness like SARS and MERS. The pathogen spreading has turned into a pandemic dissemination and increased the mortality rate. Therefore, useful information is urgently necessary for effective control of the disease. Our study shows the existence of unvarying sequence with no mutation, including ORF1ab regions in 134 high-quality filtered genome sequences of SARS-CoV2 downloaded from the GISAID database. We have detected this sequence stability by using MAUVE analysis and pairwise alignment with Global Needleman Wunsch algorithm for each two different sequences, reciprocally. They also confirmed all these results were also with the Clustal W analysis. The first 6500 bp including ORF1ab region is an unvarying sequence. According to the highest TM-score of predicted protein structure analysis, the results showed it is very similar to spike protein of feline infectious peritonitis virus strain UU4 (PDB 6JX7) depending on amino acid sequences encoded by this unvarying region, and N-acetyl-D-glucosamine is the ligand of this protein. These results have confirmed that N-acetyl-D-glucosamine could play an important role in controlling of SARS-CoV-2. Also, our molecular docking analysis data supports a strong protein-ligand interaction of N-acetyl-D-glucosamine with spike receptor-binding domain bound with ACE2 (PDB 6M0J) and RNA-binding domain of nucleocapsid phosphoprotein (PDB 6WKP) from SARS CoV-2. Therefore, binding of N-acetyl-D-glucosamine to these proteins could inhibit SARS CoV-2’s replication. In the present work, we have suggested providing a repurposing compound for further in vitro and in vivo studies and new insights for ongoing clinical treatments as a new strategy to control of SARS-CoV-2 infections.

The purpose of this study was to determine the maximum tolerated dose (MTD) for stereotactic body radiation therapy (SBRT) in the treatment of non-metastatic prostate cancer. This study was a phase 1 dose escalation trial conducted in Japan. Patients with histologically proven prostate cancer without lymph node or distant metastasis were enrolled. The prescribed doses were 42.5, 45, or 47.5 Gy in five fractions. Dose-limiting toxicity (DLT) was defined as grade (G) 3+ gastrointestinal or genitourinary toxicity within 180 days after SBRT completion and a 6 plus 6 design was used as the method of dose escalation. A total of 16 patients were enrolled, with 6 in the 42.5 Gy group and 10 in the 45 Gy group. No DLT was observed in the 42.5 Gy group. In the 45 Gy group, one patient experienced G3 rectal hemorrhage, and another had G4 rectal perforation, leading to the determination of 42.5 Gy as the MTD. None of the patients experienced biochemical recurrence or death during the follow-up period. We concluded that SBRT for non-metastatic prostate cancer at 42.5 Gy in 5 fractions could be safely performed, but a total dose of 45 Gy increased severe toxicity.

Crash prediction of the sharp horizontal curve segment (SHCS) of a freeway is an important tool in analyzing safety of SHCSs and in building a crash prediction model (CPM). The design and crash report data of 88 SHCSs from different institutions were surveyed and three negative binomial (NB) regression models and three generalized negative binomial (GNB) regression models were built to prove that the interactive influence of explanatory variables plays an important role in fitting goodness. The study demonstrates the effective use of the GNB model in analyzing the interactive influence of explanatory variables and in predicting freeway basic segments. Traffic volume, highway horizontal radius, and curve length have been formulated as explanatory variables. Subsequently, we performed statistical analysis to determine the model parameters and conducted sensitivity analysis. Among the six models, the result of model 6, which considered interactive influence, is much better than those of the other models by fitting rules. We also compared the actual results from crashes of 88 SHCSs with those predicted by models 1, 3, and 6. Results demonstrate that model 6 is much more reasonable than models 1 and 3.

The Tisza River is the longest tributary of the Danube, draining the eastern part of the Carpathian Basin (Central Europe). Five countries share its catchment with different waste production and management practices. Large amounts of waste, including macroplastics (MaPs), are washed into the river. Some of the litter is trapped by the riparian vegetation forming litter accumulations. The study aimed to map the amount of litter by a citizen science program and remote sensing data and to compare the MaP data to the amount of microplastic fragments in sediments. Volunteers reported 3216 riverine litter accumulations from five countries along the entire length of the Tisza (2016–2022). The results suggest that low flow conditions (e.g., impoundment by dams) support litter and MaP trapping. The volume of large accumulations registered by the citizens showed a good correlation with the area of drifting litter revealed on Sentinel-2 images (2015–2021) using machine learning algorithms. Though the MaPs probably fragmentate during their fluvial transport, no clear connection was found between the volume of litter accumulations and the mean microplastic fragment content of sediments (2019–2022). The “Clean Tisza Map“ reveals the high degree of stranded pollutants along rivers and supports public cleanup activities.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P < 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P < 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P < 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Background/Objectives: The aim of the project is a longitudinal assessment of body image and mental health in scoliosis females pre-, postoperatively and in a follow-up, and implementation (one group-CBT scoliosis sample, CBTSS) or not (second group-control scoliosis sample, CSS) of CBT interventions. A healthy female sample (HFS) was also selected for comparative purposes. Methods. 36 in total AIS patients participated in the 1st and 2nd study phases, whereas 23 were eligible in the follow-up. Regarding HFS, 18 participants were included in the study. The CBT intervention took place pre- and postoperatively, during the patients' stay in hospital. Participants completed the Spinal Appearance Questionnaire (SAQ), Body Esteem Scale (BES) and Strengths and Difficulties Questionnaire-25 (SDQ-25). Body image was also assessed using a virtual reality-based application “Avatar Scoliosis 3D”. Results: The difference between the desired and objective, actual body shape is significant preoperatively both in the CBTSS and CSS at p