The purpose of this paper is to evaluate the timing of innovative investment in technology product life cycles using a compound binomial option with management flexibility. Considering the business cycles changes in the macroeconomic will affect consumer purchasing power. The focus is how to evaluate the optimal investment strategy and the project value. It was applied to different product stages (three stages including production innovation, manufacture innovation, and operation innovation) and factored to different risks to build a technology innovation strategy model. An aim of this study is the options premium of the best strategy timing for each innovation stage. Its application of the compound binomial options for the manufacture innovation will only be considered after the execution of the production innovation. The same condition is applied to the operation innovation, which will only be considered after the execution of the manufacture innovation. Then, this paper constructs the dynamic investment sequential decision model, assesses the feasibility of an investment strategy, and makes a decision on the appropriate project value and options premium for each stage under the possible change of Gross Domestic Product (GDP). This paper investigates the product life cycle innovation investment topic by using the compound binomial options method and will provide a more flexible strategy decision compared with other trend forecast criteria.

The majority of EGFR mutations (85–90%) are exon 19 deletions and L858R point mutation of exon 21, characterized by high sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Less is known about uncommon mutations (10-15% of EGFR mutations). Predominant mutation types in this category include exon 18 point mutations, exon 21 L861X, exon 20 insertions and exon 20 S768I. This group presents a heterogeneous prevalence, partly due to the different testing methods and to the presence of compound mutation, which in some cases leads to shorter overall survival and different sensitivity to different TKIs than simple mutations. EGFR-TKI sensitivity may also vary depending on the specific mutation and the tertiary structure of the protein. The best strategy remains uncertain and the data of TKIs efficacy are founded of few prospective and some retrospective series. Newer investigational agents are still under study and there are no other approved specific treatment targeting uncommon EGFR mutations. Defining the best treatment option for this patient population remain un unmet medical need. The objective of this review is to evaluate existing data on outcomes, epidemiology and clinical characteristics of lung cancer patients with rare EGFR mutations, with a focus on intracranial activity and response to immunotherapy.

Microfluidic technology has become a powerful tool for several applications in chemistry, physics, biology, and engineering. Benefiting from the advantages of flowing fluids in the laminar regime, droplet-based microfluidics enable the development of various delivery systems based on food-grade emulsions, such as multiple emulsions, microgels, microcapsules, solid lipid micro-particles, and giant liposomes. Besides, by manipulating fluids on a micrometer scale with low-energy demand, it is possible to control the size, shape, and dispersity of droplets generated, which makes microfluidic emulsification an excellent strategy to modulate delivery system properties depending on the entrapped compound type. Thus, this review points out the most current advances in droplet-based microfluidic processes, in which food-grade materials were successfully utilized to develop simple and complex delivery systems. In that context, we sum-marized the principles of droplet-based microfluidics, introducing the most common microde-vices geometries, manufacturing materials, and forces involved in the different droplet generation processes within the microchannels. Subsequently, the encapsulated compound type, classified as lipophilic or hydrophilic functional compounds, was used as a starting point to present current advances in delivery systems based on food-grade emulsions and assembly using microfluidic technologies. Finally, we discuss the limitations and perspectives of scale-up in droplet-based microfluidic approaches, including the challenges that have limited the transition of microfluidic processes from lab-scale to industrial-scale.

Electronic structure calculations have been carried out to examine the effect of protonation and water molecules on the heme group of peroxidases in different redox (ferric, ferrous, compounds I and II) and spin states. Shared geometries, spectroscopic properties at Soret region, and thermodynamics of peroxidases are discussed. B3LYP and M06-2X density functionals with different basis sets were employed on a common molecular model of the active site (Fe-centred porphine and proximal imidazole). Computed Gibbs free energies indicate that the corresponding aquo complexes are not thermodynamically stable, supporting the five-coordinate Fe(III) centre in native ferric peroxidases, with a water molecule located at a non-bonding distance. Protonation of the ferryl oxygen of compound II is discussed in terms of thermodynamics, Fe–O bond distances, and redox properties. It is demonstrated that this protonation is necessary to account for the experimental data and computed Gibbs free energies that reveal pKa values of compound II about 8.5 – 9.0. Computation suggests that the origin of the general oxidative properties of peroxidase species, as well as their reactivity towards water and protons and Soret spectral properties, mostly resides on the iron porphyrin and its proximal ligand histidine.

Objective: The aim of this study was to identify and characterize the 100 most cited articles on Parkinson's disease (PD) and phenolic compounds (PCs). Methods: Articles were selected in the Web of Science Core Collection up to January 2022 based on predetermined inclusion criteria, and the following bibliometric parameters were extracted: the number of citations, title, keywords, authors, year, study design, tested PC and therapeutic target. MapChart was used to create worldwide networks, and VOSviewer software was used to create bibliometric networks. Descriptive statistical analysis was used to identify the most researched PCs and therapeutic targets in PD. Results: The most cited article was also the oldest. The most recent article was published in 2020. Asia and China were the continent and the country with the most articles in the list (55% and 29%, respectively). In vitro studies were the most common experimental designs among the 100 most cited articles (46%). The most evaluated PC was epigallocatechin. Oxidative stress was the most studied therapeutic target. Conclusion: Despite the demonstrations in laboratorial studies, the results obtained point to the need for clinical studies to better elucidate this association.

Some novel (phenyl-diazenyl)phenols (3a–g) were designed and synthesized to be evaluated for their antimicrobial activity. A previously synthesized molecule, active against bacteria and fungi, was used as lead for modifications and optimization of the structure, by introduction/removal or displacement of hydroxyl groups on the azobenzene rings. The aim of this work was to evaluate the consequent changes of the antimicrobial activity and to validate the hypothesis that, for these compounds, a plausible mechanism could involve an interaction with protein receptors, rather than an interaction with membrane. All newly synthesized compounds were analyzed by ¹H nuclear magnetic resonance (NMR), DSC thermal analysis and UV-Vis spectroscopy. The in vitro minimal inhibitory concentrations (MIC) of each compound was determined against Gram-positive and Gram-negative bacteria and Candida albicans. Compounds 3b and 3g showed the highest activity against S. aureus and C. albicans, with remarkable MIC values of 10 µg/mL and 3 µg/mL, respectively. Structure- activity relationship studies were capable to rationalize the effect of different substitutions on the phenyl ring of the azobenzene on antimicrobial activity.

Limoncella of Mattinata, a rare and ancient Mediterranean citrus fruit, was investigated by sequence analysis of the ribosomal internal transcribed spacer regions, which assigns it as a variety of Citrus medica L. Morphological, chemical, and biomolecular approaches were used to characterize flavedo and albedo, parts usually rich of bioactive compounds. The morphological findings showed albedo and flavedo cellular structures as “reservoirs” of nutritional components. Both albedo and flavedo hydroalcoholic extracts were rich in polyphenols, but they were different in compounds and quantity. The flavedo is rich in p-coumaric acid and rutin, whereas the albedo contains high levels of hesperidin and quercitrin. Antioxidant, anti-inflammatory, and genoprotective effects for albedo and flavedo were found. The results confirmed the health properties of flavedo and highlighted that albedo is also a rich source of antioxidants. Moreover, this study valorizes Limoncella of Mattinata's nutritional properties, cueing its crops' repopulation.

In recent years, compound glass microsphere resonator devices have attracted increasing interest and have been widely used in sensing, microsphere lasers, and nonlinear optics. Compared with traditional silica resonators, compound glass microsphere resonators have many significant and attractive properties, such as high-Q factor, an ability to achieve high rare earth ion, wide infrared transmittance and low phonon energy. This review provides a summary and a critical assessment of the fabrication and the optical characterization of compound glasses and the related fabrication and applications of compound glass microsphere resonators.

The presence and localization of plant metabolites are indicative of physiological processes, e.g., under biotic and abiotic stress conditions. Further, the chemical composition of plant parts is related to their quality as food or for medicinal applications. Mass spectrometry imaging (MSI) has become a popular analytical technique for exploring and visualizing the spatial distribution of plant molecules within a tissue. This review provides a summary of mass spectrometry methods used for mapping and identifying metabolites in plant tissues. We present the benefits and the disadvantages of both vacuum and ambient ionization methods, considering direct and indirect approaches. Finally, we discuss the current limitations in annotating and identifying molecules and perspectives for future investigations.

Now day; the interest for the synthesis of heterocyclic compounds containing hydroquinoline fragments has increased tremendously due to their wide variety of pharmaceutical and industrial applications. This work details the synthesis of linear and fused heterocyclic systems containing hydroquinoline fragments and the pharmacological activity spectra of the synthesized compounds was predicted by in silico method using Prediction of Activity Spectra of Substances (PASS) program. 1,2,2,4-tetramethyl-1,2-dihydroquinoline-6-carbaldehyde 5a was reacted for three hours with a system of hydroxylammonium chloride/pyridinium chloride/toluene to produce 1,2,2,4-tetramethyl-1,2-dihydroquinoline-6-nitrile 7. N-benzyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-carbaldehyde 6b and iodine reacted at room temperature in aqueous ammonia water, followed by aq. treatment with Na2S2O3 and produced N-benzyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-nitrile 8. 30-60% 2-phenyl-1,3-oxazol-5(4H)-ones 9a,b; 10a,b were synthesized via the condensation reaction of N-alkylhydroquinoline-6-carbaldehydes 5a,b; 6a,b with hippuric acid in acetic acid. When activated 7-methylazolopyrimidines 11a,b were reacted with N-alkyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-carbaldehydes 6a,b, the reaction produced 60–70% yield of 7-[(E)-2,2,4-trimethylhydroquinolin-6-ylidenemethyl]azolo[1,5-a]pyrimidin-6-yl carboxylic acids 12a,b. The condensation reaction of 7-hydroxy-1,2,2,4-tetramethyl-1,2-dihydroquinoline 3h with dimethylacetylenedicarboxylate (DMAD) and ethylacetoacetate afforded methyl (Z)-2-(5,7,7,8-tetramethyl-2-oxo-7,8-dihydrofuro[3,2-g]quinolin-3(2H)-ylidene)acetate 16 and 4,6,8,8,9-pentamethyl-8,9-dihydro-2H-pyrano[3,2-g]quinolin-2-one 17, respectively. The condensation reaction of 6-formyl-7-hydroxy-1,2,2,4-tetramethyl-1,2-dihydroquinoline 5e with methylene active compounds ethylcyanoacetate/dimethyl-3-oxopentanedioate/ ethylacetoacetate/diethylmalonate/Meldrum’s acid afforded 3-substituted dihydroquinoline containg coumarins 19 & 21. A pentacyclic coumarin 22 was obtained via the random condensation reaction of malononitrile with 5e in the presence of catalytic amount of piperidine in ethanol. The potential biological activities of the synthesized compounds were evaluated using PASS computer program. According to the prognosis, (E)-4-(N-alkylhydroquinolin-6-yl)-3-buten-2-ones, 13a, b & 14 showed high probability of being active (Pa) as the Gluconate 2-dehydrogenase inhibitor, Anti-allergic, Anti-asthmatic, and Anti-arthritic with the Pa value of 0.849-0.870. It was also found out that hydroquinolinecarbonitrile compounds 7 & 8 have a propensity to act as a good progesterone antagonists, anti-allergic, anti-asthmatic, and anti-arthritic (Pa = 0.276-0.827). Among the coumarin moieties containing hydroquinolines, compounds 17, 19a, and 19c were predicted to be good progesterone antagonists with the Pa values of 0.710, 0.630 and 0.615; respectively.

Structurally clear compounds have advantages for quality control in plant biostimulant production and application processes. Humic acid (HA) is a biostimulant that significantly affects plant growth, and soil-dwelling Protaetia brevitarsis larva (PBL) can rapidly convert agricultural waste into HA. In this study, we use PBL as a model to investigate HA formation and screen for HA-related structurally clear plant biostimulant compounds. The dephasing magic angle spinning nuclear magnetic resonance (13C DD–MAS NMR) analysis indicated HA structural changes during PBL digestion; the metabolic profile detected seven HA-related aromatic ring-containing compounds. Plant experiments identified six compounds with stimulating effects, with piperic acid being reported for the first time in this study. Thus, this study not only provides insights into the insect-mediated transformation of HA but also illustrates a new strategy for discovering structurally clear plant biostimulant compounds.

Smallholder dairying engages around 70 to 80 million rural households who are mostly landless, small and marginal farmers. These farmers face challenges in terms of adoption of balanced feeding practices including inclusion of compound feed in animal feeding. This necessitates to understand the socio-economic factors that are influencing the adoption of compound feed. The study found that 51% of dairying households adopted compound feed in animal feeding. The adopters and non-adopters of compound feed differed (P< 0.01) in terms of land holding, family educational status, breeds owned, membership status in farmer’s collectives, fodder adoption, area under fodder, access to grazing resources, availability of crop residues, milk production and milk marketing opportunities. Furthermore, users and non-users of compound feed had significant difference (P< 0.05) in extension agency contact, mass media contact, attitude towards dairying and gender participation in farming. The logit regression model explained the variance in adoption to 30%. Further it indicated the role of selective socio-economic characters, farming situations, feeding and marketing practices in adoption of compound feed. In specific membership in farmer’s collectives, marketing opportunity, milk production, farm men participation, family education status, grazing resources and attitude towards dairying has greatly influenced the adoption behaviour of compound feed in positive direction. Added, households with high experience, cultivating fodder and having access to crop residues tend to influence the adoption decision negatively. The research observed that farmers tend to use compound feed for increasing productivity in areas of better markets and there exists trade-offs between milk market opportunities, access to cheaper roughages and usage of compound feed.

To realize the diagnosis of compound faults in gearboxes at different speeds, an "end-to-end" intelligent diagnosis method based on a deep neural network is proposed, named efficiency channel attention-capsule network (ECA-CN). First, the process uses a deep convolutional neural network to extract fault features from the collected raw vibration signals, then embeds the efficient channel attention module to filter important fault features, then uses the capsule network to vectorize the feature space information, and finally calculates the correlation between different levels of capsules by the dynamic routing algorithm to achieve accurate gearbox compound fault diagnosis. The effectiveness of the proposed ECA-CN fault diagnosis method was verified by the composite fault dataset of the 2009 PHM Challenge gearbox, with an average accuracy of 99.63% and a standard deviation of 0.22%. In the comparison experiments with the traditional fault diagnosis method, the average accuracy of the ECA-CN method was improved by 4.62%, and the standard deviation was reduced by 0.58%. The experimental results show that ECA-CN has a more competitive diagnostic performance.

From 2020 to 2023 many people around the world were forced to wear masks for large proportions of the day based on mandates and laws. We aimed to study the potential of face masks for the content and release of inanimate toxins. A scoping review of 1003 studies was performed (database search in PubMed/MEDLINE, qualitative and quantitative evaluation). Twenty-four studies were included (experimental time 17 min to 15 days) evaluating content and/or release in 631 masks (273 surgical, 228 textile and 130 N95 masks). Most studies (63%) showed alarming results with high micro- and nanoplastics (MPs and NPs) release and exceedances could also be evidenced for volatile organic compounds (VOCs), xylene, acrolein, per-/polyfluoroalkyl substances (PFAS), phthalates (including di(2-ethylhexyl)-phthalate, DEHP) and for Pb, Cd, Co, Cu, Sb and TiO₂. Of course, masks filter bacteria, dirt and plastic particles and fibers from the air we breathe and have specific indications, but according to our data they also carry risks. Depending on the application, a risk-benefit analysis is necessary. However, mask mandates during the SARS-CoV-2 pandemic have been generating an additional source of potentially harmful exposition to toxins at population level with almost zero distance to the airways.

The Canadian Prairies are associated with high natural hydroclimatic variability including the frequent periodic occurrence of droughts and pluvials. These extremes carry various risks in-cluding significant damage to the economy, environment and society. The well-documented level of damage necessitates further risk assessment and planned reductions to vulnerability, particu-larly in light of a warming climate. A logical starting point involves awareness and information about the changing characteristics of such climate extremes. We focus on the compound occurrence of droughts and pluvials as the risks from this type of event are magnified compared to the hy-droclimatic extremes in isolation. Also, research on compound droughts and pluvials is limited. Therefore, the purpose of this paper is to synthesize recent literature concerning the risks of com-pound droughts and pluvials, including examples of past occurrences, with a focus on the Cana-dian Prairies. Since literature from the Prairies is limited, global work is also reviewed. Rela-tionships between drought and pluvials are characterized using the SPEI Global Monitor for the Prairies, emphasizing the recent past, and through synthesis from the Prairie literature. That re-search mostly considers drought and pluvials as separate events, but is integrated here to charac-terize the relationships of these extremes. Examples of periods of compound droughts and exces-sive rainfall provide insights into the regional hydroclimatic variability. Furthermore, most lit-erature on future projections strongly suggests that this variability is likely to increase, mainly driven by anthropogenic climate change. These findings suggest means of decreasing vulnerabil-ity and associated damages. Although the study area is the Canadian Prairies, the work is rele-vant to other regions that are becoming more vulnerable to increasing risks of and vulnerabilities to such compound extremes.

Concerns regarding the safety of ethoxyquin (EQ) have gradually increased, highlighting the necessity of identifying safer and more effective antioxidants for use in animal feed. This study investigates the effects of a compound antioxidant (CA) as an alternative to ethoxyquin on feed oxidative stability, growth performance, antioxidant capacity, and intestinal health in broilers. A total of 351 one-day-old Arbor Acres Plus male broilers were randomly assigned to three treatments with nine replicates of 13 birds each. The experimental treatments included: CON group (basal diet), EQ group (basal diet + 200 g/ton EQ at 60% purity), and CA group (basal diet + 200 g/ton compound antioxidant, which comprises 18% butylated hydroxytoluene, 3% citric acid, and 1% tertiary butylhydroquinone). The experiment lasted for 21 days. Compared to the control group, supplementation with CA significantly reduced the acid value, peroxide value, and malondialdehyde content in the feeds after storage. Moreover, CA supplementation significantly decreased feed intake and the feed conversion ratio (FCR) without affecting weight gain of boilers, while also improving liver antioxidant capacity (increased T-AOC and SOD levels), intestinal antioxidant capacity (increased CAT, HO-1, and GPX7 protein expression), and enhancing the duodenal villus height-to-crypt depth ratio and jejunal villus height. Additionally, CA treatment reduced intestinal barrier permeability (decreased diamine oxidase activity and D-lactate levels), potentially by promoting the expression of Occludin, ZO-1, and Mucin2 protein. Furthermore, the addition of CA elevated the protein levels of NF-κB p50 along with its inhibitory factors, IκB and NF-κB p105, in the intestines of broilers, thereby enhancing immune regulatory capacity. This supplementation also led to an increased abundance of beneficial gut microorganisms, including Lactobacillus, Alistipes, Candidatus Arthromitus, and Turicibacter. In comparison to the EQ group, CA supplementation enhanced feed oxidative stability, decreased the FCR, and improved the intestinal morphology, barrier functions, and inflammatory status in broilers. These findings suggest that this compound antioxidant may serve as a healthier and more effective alternative to ethoxyquin.

Renal cancer is a common and serious malignant tumor of the urinary system. While surgery effectively treats early-stage renal cancer, advanced cases pose a significant challenge due to poor treatment outcomes and chemotherapy resistance. Therefore, there is an urgent need to develop alternative therapeutic strategies. Ferroptosis is a newly defined form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which plays a critical role in tumor progression and drug resistance. Recent studies have shown that ferroptosis is involved in the occurrence and development of renal cancer, ferroptosis related genes can induce cell apoptosis, and can be used as potential biomarkers for early diagnosis of renal cancer and participate in drug resistance of renal cancer chemotherapy. With the continuous improvement of the mechanism of ferroptosis, drugs targeting ferroptosis for the treatment of renal cancer are emerging in an endless stream, Based on the theoretical basis of the occurrence of ferroptosis, this paper reviewed drug-induced ferroptosis in renal cancer cells from the aspects of herbal medicine, natural compounds, drug resistance mechanisms, and nanomaterials, hoping to provide a new strategy for the treatment of renal cancer with ferroptosis related drugs.

Cancer is a devastating disease with female breast cancer becoming the leading cause of global cancer morbidity. Herein we report the design and synthesis of a sorafenib analog 1A and its base-promoted arranged compound 1A2. Their in vitro cytotoxicity and potencies in EFGR inhibition study revealed that compound 1A displayed good antiproliferative activity in MDA-MB-231 (breast) cells with an IC50 value of 16.18±1.42 μM. Crystallization 1A2 affored 1A2a as a solvate with dichloromethane which was explicitly confirmed by the single crystal X-ray diffraction analysis.

We are currently investigating the ultrasound imaging of a sensor consisting of a randomized encoding mask attached to a single lead zirconate titanate (PZT) oscillator for use in a puncture microscope. The proposed model was performed using a finite element method (FEM) simulator. To increase the number of measurements required by a single element system, the transducer was rotated at different angles. The image was constructed by solving a linear equation of the image model. In a previous study, the image resolution was improved by extracting phase information. In this study, we propose a strategy by integrating the weighted frequency subbands compound and a super resolution method (SCM) to improve the resolution in range and lateral resolution. We also evaluated the image performance by applying different methods to improve the image quality. The results show that better image resolution and speckle suppression were obtained by applying the proposed method.

Magnaporthe oryzae Triticum (MoT) pathotype is the causal agent of wheat blast, which has caused significant economic losses and threatens wheat production in South America, Asia and Africa. Three bacterial strains from rice and wheat seeds (B. subtilis BTS-3, B. velezensis BTS-4, and B. velezensis BTLK6A) were used to explore the antifungal effects of volatile organic compounds (VOCs) of Bacillus spp. as a potential biocontrol mechanism against MoT. All bacterial treatments significantly inhibited both mycelial growth and sporulation of MoT in vitro. We found that this inhibition was caused by Bacillus VOCs in a dose-dependent manner. In addition, biocontrol assays using detached wheat leaves infected with MoT showed reduced leaf lesions and sporulation compared to the untreated control. VOCs from B. velezensis BTS-4 alone or a consortium (mixture of B. subtilis BTS-3, B. velezensis BTS-4, and B. velezensis BTLK6A) treatments consistently suppressed MoT in vitro and in vivo. Compared to the untreated control, VOCs from BTS-4 and Bacillus consortium reduced MoT lesions in vivo by 85% and 81.25%, respectively. A total of thirty-nine VOCs (from 9 different VOC groups) from 4 Bacillus treatments were identified by gas chromatography-mass spectrometry (GC-MS), of which 11 were produced in all Bacillus treatments. Alcohols, fatty acids, ketones, aldehydes, and S-containing compounds were detected in all four bacterial treatments. In vitro assays using pure VOCs revealed that hexanoic acid, 2-methylbutanoic acid, and phenylethyl alcohol are potential VOCs emitted by Bacillus spp. that are suppressive for MoT. The minimum inhibitory concentrations for MoT sporulation were 250 mM for phenylethyl alcohol and 500 mM for 2-methylbutanoic acid and hexanoic acid. Therefore, our results indicate that VOCs from Bacillus spp. are effective compounds to suppress the growth and sporulation of MoT. Understanding the MoT sporulation reduction mechanisms by Bacillus VOCs may provide novel options to manage the further spread of wheat blast by spores.

We report a very frugal microscope building method from easily realizable parts. We show a highly portable field ready compound type microscope with bright field, dark field and projection microscopy capabilities. It has good resolution and magnification for multiple aspects of education and diagnosis. We demonstrate that such a system can be built from simple lenses in laser pointers and camera modules with no specific 3d printed parts or costly lenses. We show all the parts of the system like stage, coarse and fine focussing system, microscope body, even slides can be built from commonly available materials like soda bottle and DVD disks. We list alternate, safer and easily available staining methods and chemicals. The microscope is developed with a target that it can be self-developed even in rural areas of the world with only resources at one’s disposal with very little education. This features a stable focussing and panning system for comfortable viewing through eyes and also easy imaging with a smartphone. We show its utility for microorganism analysis and potential for clinical diagnosis.

Obesity is a universal health concern that can lead to serious diseases. The side effects of synthetic anti-obesity drugs necessitate the finding of suitable natural/herbal alternatives. Mother nature offers a wide range of plants with medicinal properties that include crude extracts and isolated compounds which are effective for controlling and reducing weight gain. Obesity was induced in 60, 3-week-old male ICR mice, using high-fat diet (60% dietary energy from fat) for 16-week. The mice were divided at random into six groups with 10 mice: mice fed with high-fat diet (HFD) only, mice fed normal diet only (NC), and orlistat at 15.9 mg/kg (HFD+Orlistat), and mice in three other high-fat diet groups treated with methanolic leaf extract of Clinacanthus nutans (MECN) at 500, 1000 and 1500 mg/kg. After 21-day of the treatment, MECN significantly reduced (P<0.05) the body weight, visceral fat and muscle saturated fatty acid compositions. There was also significant downregulation of HSL, PPAR α and PPAR γ and SCD genes expressions in the obese mice treated with 1500 mg/kg MECN compared to the HFD group. Therefore, MECN is a potentially useful natural supplement for alleviating obesity and obesity-mediated metabolic diseases.

Layered superconductors are attractive because some of them show high critical temperatures. While their crystal structures are similar, those compounds are composed of many elements. Compounds with many elements tend to be incongruent melting compounds, thus, their single crystals cannot be grown via the melt-solidification process. Hence, these single crystals have to be grown below the decomposition temperature, and then the flux method, a very powerful tool for the growth of these single crystals with incongruent melting compounds, is used. This review shows the flux method for single-crystal growth technique by self-flux, chloride-based flux, and HPHT (high-pressure and high-temperature) flux method for many-layered superconductors: high-T_c cuprate, Fe-based and BiS₂-based compounds.

The structure of arylpiperazine moieties as an important pharmacophore could generate wide pharmacological activities．Arylpiperazine derivatives referred in this paper possessed antitumor activity. The title compounds were crystallized by slow evaporation. 2-(4-(2-(4-Phenylpiperazin-1-yl)ethyl)benzyl)isoindoline-1,3-dione(1), 2-(4-(2-(4-(4-Bromophenyl)piperazin-1-yl)ethyl)benzyl)isoindoline-1,3-dione (2) and 2-(4-(2-(4-(4-Chlorophenyl)piperazin-1-yl)ethyl)benzyl)isoindoline-1,3-dione (3) crystallizes in the triclinic space group P-1 with two molecules in the unit cell. The unit cell parameters for 1 are a = 6.9159(14) Å, b = 9.999(2) Å, c = 16.925(3) Å, α = 88.25(3)°, β = 85.14(3) °, γ = 79.22(3) °. The unit cell parameters for 2 are a = 6.9995(14) Å, b = 9.919(2) Å, c = 17.671(4) Å, α= 97.55(3)°, β = 92.19(3) °, γ = 102.23(3) °. The unit cell parameters for 1 are a = 6.9872(14) Å, b = 9.863(2) Å, c = 17.557(4) Å, α=96.81(3)°, β = 91.89(3) °, γ = 101.74(3) °. Pi-pi interactions were observed between molecules, and compound 2 and 3 showed halogen interactions between molecules nearby, which was different from compound 1.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder marked by progressive motor and non-motor symptoms. Traditional treatments primarily manage symptoms rather than address the disease's root causes, highlighting the need for novel therapeutic approaches. Natural phytochemicals, particularly phenolic compounds, have shown potential due to their neuroprotective effects. Antiaris africana is commonly used in traditional African medicines to treat several illnesses including neurodegenerative disorders. However, its neuroprotective mechanism remains elusive. This study aimed to employ network pharmacology-based prediction to identify key targets and pathways through which A. africana exerts its effects on PD. Targets associated with Parkinsonism were identified and analyzed for interaction with compounds from A. africana. Protein-protein interaction (PPI) networks were constructed, and key hub genes were identified using Cytoscape. Functional enrichment analysis highlighted significant pathways involved in PD. Molecular docking was performed to evaluate the binding affinities of the compounds to PD-related targets. Our results reveal that compounds such as caffeic acid, chlorogenic acid, catechin, ellagic acid, epigallocatechin, gallic acid, isoquercitrin, kaempferol, quercetin, quercitrin, and rutin interact with key proteins implicated in PD, including APP, EGFR, CASP3, ESR1, AKT1, and MAPK8. Notably, rutin exhibited strong binding affinity for EGFR, and chlorogenic acid showed potential in modulating the APP pathway. These findings suggest that phenolic compounds in A. africana may exert neuroprotective effects through multiple molecular mechanisms, offering potential therapeutic strategies for PD. This study underscores the importance of integrating molecular docking and network pharmacology to elucidate the therapeutic potential of natural compounds in complex diseases like Parkinson's disease

Diabetes mellitus (DM) is a metabolic disorder characterized by the deficiency of insulin production and is one of the concerning health problems worldwide, especially in developing countries. Considering the systemic toxicity associated with current antidiabetic medications and their limited efficacy, there is an urgent need to discover new plant-based natural antidiabetics. Since time immemorial, medicinal plants have played an important role in the management of health disorders. In recent years, herbal medicine has experienced exponential growth in popularity worldwide, owing to its natural origin and fewer side effects, appealing to both developing and developed nations. Ecuador has a rich cultural history in ethnobotany that plays a crucial role in their people's lives. Several Ecuadorian medicinal plants have hypoglycemic or an-ti-hyperglycemic properties that are rich with bioactive phytochemicals. These medicinal plants were extensively used in traditional medicine preparation in Ecuador for many decades to treat diabetes because of their cost-effectiveness, available traditional knowledge, and low toxicity. Many Ecuadorian medicinal plants are reported to have antidiabetic properties that reduce blood sugar levels, and oxidative stress, regulate intestinal function, improve insulin resistance, inhibit α-amylase and α-glucosidase, lower gluconeogenic enzymes, stimulate glucose uptake mechanisms, and play an important role in glucose and lipid metabolism, yet there is a substantial lack of integrated approach between the existing ethnomedicinal practice and pharmacological research. Therefore, this review aims to discuss and explore the traditional medicinal plants used in Ecuador for treating DM and their bioactive phytochemicals, which are mainly responsible for their anti-diabetic properties.

Two new coordination compounds of Mn(II) and Cu(II) viz. [Mn(bz)2(Hdmpz)2(H2O)] (1) and [Cu(crot)2(Hdmpz)2] (2) (where, bz = benzoate, crot = crotonate, Hdmpz = 3, 5-dimethyl pyrazole) have been synthesized and characterized using single crystal X-ray diffraction technique, FT-IR, electronic spectroscopy, TGA and elemental analyses. Compounds 1 and 2 crystallize as mono-nuclear coordination compounds of Hdmpz based penta-coordinated Mn(II) and hexa-coordinated Cu(II) respectively containing distorted trigonal bipyramidal and distorted octahedral geome-tries. Crystal structure analysis of compound 1 reveals the presence C‒H⋯π and π-stacking in-teractions along with O‒H⋯O, N‒H⋯O and C‒H⋯O H-bonding interactions which stabilizes the layered assembly of the compound. Similarly, the presence of hydrogen bonding along with π-stacking interactions stabilizes the crystal structure of compound 2. We have carried out theo-retical investigations to analyze π⋯π H-bonding and antiparallel CH···π non-covalent interac-tions observed in the compounds. DFT calculations were performed to evaluate strength of these interactions energetically. Moreover, QTAIM and non-covalent interaction (NCI) plot index computational tool were used to characterize them and evaluate the contribution of the H-bonds.

Rare ginsenoside compound K (CK), is an intestinal microbial metabolite with a low natural abundance that is primarily produced by physicochemical processing, side chain modification, or metabolic transformation in the gut. Moreover, CK exhibits potent biological activity compared to primary ginsenosides, which has raised concerns in the field of ginseng research and development as well as ginsenosides-related dietary supplements and natural products. Ginsenosides Rb1, Rb2, and Rc are generally used as a substrate to generate CK via several bio-conversion processes. Current research shows that CK has a wide range of pharmacological actions including boosting osteogenesis, lipid and glucose metabolism, lipid oxidation, insulin resistance, anti-inflammatory, and anti-apoptosis properties. Further research on the bioavailability and toxicology of CK can advance its medicinal application. The purpose of this review is to lay the groundwork for future clinical studies and the development of CK as a therapy for metabolic disorders. Furthermore, the toxicology and pharmacology of CK are investigated as well in this review. The findings indicate that CK primarily modulates signal-ing pathways associated with AMPK, SIRT1, PPARs, WNTs, and NF-kB. It also demonstrates a positive therapeutic effect of CK on nonalcoholic fatty liver disease, obesity, hyperlipidemia, diabetes, and its complications, as well as osteoporosis. Additionally, the analogues of CK showed more bioavailability, less toxicity, and more efficacy against disease states. Enhancing bioavailability and regulating hazardous variables are crucial for its use in clinical trials.

The traditional understanding of brain function has predominantly focused on chemical and electrical processes. However, new research in fruit fly (Drosophila) binocular vision reveals ultrafast photomechanical photoreceptor movements significantly enhance information processing, thereby impacting a fly's perception of its environment and behaviour. The coding advantages resulting from these mechanical processes suggest that similar physical motion-based coding strategies may affect neural communication ubiquitously. The theory of neural morphodynamics proposes that rapid biomechanical movements and microstructural changes at the level of neurons and synapses enhance the speed and efficiency of sensory information processing, intrinsic thoughts, and actions by regulating neural information in a phasic manner. We propose that morphodynamic information processing evolved to drive predictive coding, synchronising cognitive processes across neural networks to match the behavioural demands at hand effectively.

Ovarian cancer is the common cause of death among gynecological cancers. Although ovarian cancer initially responds to chemotherapy, the frequent recurrence in patients remains a therapeutic challenge. Pyruvate kinase M2 (PKM2) plays a pivotal role in regulating cancer cell survival. However, its therapeutic roles remain unclear. Here, we investigated the anticancer effects of compound 3K, a specific PKM2 inhibitor, on autophagic and apoptotic pathway regulation in SK-OV-3 (PKM2-overexpressing human ovarian adenocarcinoma cell line). The anticancer effect of compound 3K was examined using the MTT and colony formation assay in SK-OV-3. The results of tissue microarray showed that PKM2 expression positively correlated with the severity of the tumor. Moreover, the expression of pro-apoptotic proteins increased in SK-OV-3 following compound 3K treatment. Compound 3K induced AMPK activation, which was accompanied by the inhibition of mTOR. Additionally, this compound inhibited glycolysis, resulting in reduced proliferation in SK-OV-3. Compound 3K treatment suppressed tumor progression in vivo xenograft model. Our findings suggest that the inhibition of PKM2 by compound 3K affected Warburg effects and induced autophagic cell death. Therefore, the use of specific PKM2 inhibitors to block the glycolytic pathway and target cancer cell metabolism represents a promising therapeutic approach for treating PKM2-overexpressing ovarian cancer.

When the power converter connected to the high-frequency transformer breaks through the bottleneck and reaches a frequency of 100kHz or even higher, the high-frequency transformer's inter-turn insulation faces more serious high-frequency discharge and high temperature problems. In order to improve the service performance of oil-immersed high-frequency transformer insulation paper, composite K-BNNSs particles are prepared by ultrasonic stripping, heat treatment and thermomagnetic stirring. Then, K-BNNSs particles are mixed with PMIA slurry to produce composite aramid paper. And the effects of K-BNNSs particles with different contents on the thermal conductivity, dielectric properties, partial discharge properties and mechanical properties of aramid paper are explored. It can be found that when the addition of composite particles (K-BNNSs) is 10%, the comprehensive performance of composite aramid paper is the best. Compared with Nomex paper, the in-plane and through-plane thermal conductivity of composite insulating paper F-10 is increased by 668.33% and 760.66% respectively. Besides, the high-frequency breakdown voltage is increased by 48.73% and the tensile strength is increased by 2.49%. The main reason is that the composite particles form a complete thermal conductive network in the aramid paper matrix and a large number of hydrogen bonds with the matrix, which enhances the internal interface bonding force of the material and changes the charge transport mechanism.

Acting as the most abundant and widely distributed volatile secondary metabolites in plants, terpenoids play crucial roles in diverse physiological regulations and metabolic processes. Terpene synthases occupy a decisive proportion in determining the composition and diversity of terpenoids; though their regulatory effects have been extensively investigated across various plant species, limited studies have focused on the upstream transcriptional regulation of terpene synthases. In this study, we unveil linalool as the predominant volatile compound in Freesia hybrida flowers, demonstrating a gradual release pattern during flower blooming. In the context of the transcriptome, a typical MYB transcription factor, FhMYB108, was screened based on digital expression profile correlation analysis and homologous gene comparison. FhMYB108 is capable of regulating the expression of terpene synthase FhTPS1, and both their expression levels exhibit a gradual increase concomitant with flower opening. Moreover, transcriptional regulation and transient expression assays revealed that FhMYB108 exerts a stimulatory effect on the transcription of A. thaliana AtTPS14, while no significant increase in AtTPS14 expression was observed upon stabilization of FhMYB108 in Arabidopsis. Investigate its reason, the highly expressed AtMYC2 in A. thaliana can interact with FhMYB108 to suppress the activation of AtTPS14 by FhMYB108. The present study not only elucidated the regulatory mechanism underlying linalool synthesis, but also discovered the synergistic effect of MYB and bHLH transcription factors in governing the biosynthesis of volatile terpenoids.

Jatropha multifida L. is a plant belong to Euphorbiaceae family used in Benin pharmacopoeia because of its medicinal properties. The objective of this work is to appreciate the therapeutic power of this plant through the evaluation of some of its biological activities. After the preliminary phytochemistry, the polyphenols and flavonoids were quantified and identified by the LC-MS-ESI. The antimicrobial power of the extracts was investigated by agar medium diffusion. The antioxidant power of the extracts was evaluated by the reduction of the DPPH radical, the ABTS radical cation, the feric ion (FRAP) and the lipid peroxidation (LPO). Anti-inflammatory activity was assessed by inhibition of protein (albumin) denaturation. Indeed, different phenolic and flavonoid compounds namely, 2-Hydroxybenzoic acid, o-Coumaroylquinic acid, Apigenin-apiosyl-glucoside, Luteolin-galactoside, Luteolin-glucoside, Luteolin-rhamnoside, Quercetin-glucoside, Quercetin-arabinoside, Dicaffeoyquinic acid, Kaempferol-rhamnoside were identify. The J. mutifida extracts has a bactericidal effect with reference strains of wich CMBs vary from 22.67 mg/ml (S. aureus, S. enteridis, L. monocytogenes and C. albicans) to 47.61 mg/ml (E. coli) and with the meat isolated strains (S. equorum, S. saprophiticus, S. haemoliticus, S. cohnii and S. lentus). Ethanolic extract show the highest DPPH radical scavenging activity (IC₅₀ = 0.72±0.03 mg/ml) while methanolic extract showed the highest ferric ion reduction (46.23±1.10 µgEAA/g). Contrary to the FRAP method, the reducing power with ABTS method of water-ethanolic extract was greater (0.49±0.11 mol ET/g). The same extract show the highest albumin denaturation inhibition power (97.31±0.35%) at 1000µg/ml. J. multifida extracts are rich in bioactive compound with good biological activity

A new class of tetrasubstituted imidazole based compounds was synthesized using a multicomponent one-pot synthesis scheme through a cyclo condensation reaction of benzil, aromatic primary amines, aldehydes and ammonium acetate in glacial acetic acid. The synthesized compounds have been analyzed and characterized by melting point, color, conductivity method, CHN analysis, FT-IR, and UV-Visible. The reaction proceeding was examined by TLC after regular intervals of period. To test biological activity, the synthesized compounds have been examined against various bacterial strains. From the analysis of the antibacterial activity of these synthesized compounds demonstrated that all three imidazole compounds have considerable to significant activity against the strains, and compound K2 was found potent comparatively.

The procedures for the extraction and separation of lipids and nutraceutics from microalgae using classic solvents have been used many times. However, these production methods usually require expensive and toxic solvents. Based on our studies involving the use of eco-sustainable methodologies and alternative solvents, we select ethanol (EtOH) and cyclopentyl methyl ether (CPME) for extracting bio-oil and lipids from algae. Different percentage of EtOH in CPME favors the production of an oil rich of SFA useful to production biofuel or rich of compounds bioactive. The proposed method for obtain a rich extract of saturated or unsaturated fatty acids from dry algal biomass is disclosed is eco-friendly and allows a good extraction yield. The method is compared both in extracted oil percentage yield and in extracted fatty acids selectivity to extraction by supercritical carbon dioxide.

Reggio Calabria province (South Italy) is known for being almost the only area of cultivation of the bergamot fruit, grown principally for its essential oil, but today much studied for the health benefits of its juice. The biometrics and physico-chemical properties of the three (Citrus bergamia Risso) existing genotypes namely Castagnaro, Fantastico and Femminello were studied during fruit ripening from October to March. Castagnaro cv had the biggest and heaviest fruit during this harvest period. °Brix (7.9-10.0), pH (2.2-2.8) and Formol number (1.47-2.37 mL NaOH 0.1N/100mL) were shown to be influenced by both the genotype and by the harvest date. Titratable acidity (34.98-59.50 g/L) and Vitamin C (Ascorbic acid) (341-867 g/L) decreased during fruit ripening. The evolution of flavonoids such as neoeriocitrin, naringin, neohesperidin brutieridin and melitidin was studied both in bergamot juice and in the bergamot cloudy which is the aqueous extract of bergamot during fruit processing. Bergamot cloudy contained a higher quantity of flavonoids compared to the juice. This study gives important information regarding the cultivar and the harvest date for producers who want to obtain the highest juice quantity or the highest juice quality from the bergamot fruit.

Joining of aluminium alloys to steels has been extensively studied, especially in the automotive sector. However, aluminium alloys are known to be difficult to join with steels when methods involving fusion welding are used because of hot cracking problem. Hence, a high strength joint between these dissimilar metals would be of benefit especially in reducing the weight of products. In this work the torch brazing method was applied to join AR500 steel with AA7075 aluminium alloy using Al-Si-Zn base filler metal at various flame times. The effect of the brazing work on the intermetallic phase formation and the mechanical strength of the joints were investigated. In this work, the maximum shear load obtained was 6460 N and the presence of the intermetallic phases had reduced the shear strength of the brazed joints. However, the torch brazing process using Al-Si-Zn filler metal had successfully facilitated the joining of these dissimilar metals.

Endocrine disruptor compounds are exogenous agents able to interfere with a gland function, exerting their action across different functional passages, from the synthesis to the metabolism and binding to receptors of the hormone produced. Several issues such as different levels and time of exposure and different action across different ages as well as gender, make the study of endocrine disruptors still a challenge. Thyroid is very sensitive to the action of disruptors, and considering the importance of a correct thyroid function for physical and cognitive functioning, addressing this topic should be considered a priority. In this review we examined the most recent studies, many of them concentrating on maternal and child exposure, conducted to assess the impact of industrial chemicals which showed an impact on thyroid function. So far, the number of studies conducted on that topic is not sufficient to provide solid conclusions and lead to homogeneous guidelines. The lack of uniformity is certainly due to differences in areas and populations examined, the different conditions of exposures and the remarkable inter-subject variability. Nonetheless, the European Commission for Health and Food Safety is implementing recommendations to ensure that substances identified as endocrine disruptors will be withdrawn from the market.

To better understand effects of agronomic practices on yield-nutrition relationships in wheat (Triticum aestivum L.) grains for Zn biofortification while improving yields simultaneously, effects of different soil fertilization and different drone-based foliar spraying treatments were investigated. The mixture of Zn or increasing N but simultaneously reducing P in compound fertilizers were all practical to increase grain yields and Zn concentrations in calcareous soils tested. However, the overall effects are limited, with a maximal yield increase by only 7.0% and a maximal increase of the grain Zn density from 19.4 to 27.0 mg/kg, which is far below the target biofortification value of 40-50 mg/kg. Unfortunately, there was a negative side effect, which decreased Fe and Mn concentrations and the Fe bioavailability. Notably, grain yields and Zn concentrations were significantly increased by drone-based foliar Zn sprayings from 7.5 to 8.6~8.8 t/ha by 12.0-17.3% and from 33.5 to 41.9~43.6 mg/kg by 25.1~30.1%, respectively, indicating a double-win in yield and nutrition. A spraying of ZnSO4·7H2O increased grain Zn concentrations and accumulation more so than ZnO, indicating the importance of chemical Zn forms in determining the effectiveness of foliar spraying. Moreover, foliar Zn sprayings simultaneously increased grain concentrations and accumulation of Fe, Mn and Cu, demonstrating multiple benefits. There were positive correlations between Zn and Fe, Mn or Cu, indicating synergistic but not antagonistic interactions. Compared to micronutrients, concentrations of grain macro- and medium nutrients (N, P, K, Ca, Mg) were less affected. Thus, a double-win in grain yields and micronutrient (particulaly for Zn) nutrition could be effectively achieved through appropriate soil fertilization and foliar Zn spraying. These results provide a better understanding of the yield-nutrition relationship among wheat grain yields, Zn and other nutrient elements for a better integrated manipulation to achieve a win-win situation in yield and nutrition.

Buckwheat is important not only as a crop that improves soil quality and reduces erosion, but its excellent nutritional profile for usage in functional foods. This study aimed to investigate how long-term storage (3, 6, and 9 months) affects Novosadska variety buckwheat's chemical, nutritional, and antioxidative properties, phenolic acids and bioflavonoids profiles. Standard traditional methods were used for quality determinations, and instrumental (spectrophotometry, reverse-phase high performance liquid chromatography) for antioxidant activity and bioactive compounds determination. One-way ANOVA, and Tukey’s HSD post-hoc were performed for statistical data processing. Throughout the storage period, proximate composition and starch content significantly decreased (p&lt;0.05), while total carbohydrates, β-glucan, and energy value significantly increased (p&lt;0.05). Significant decrease in pH and alcoholic acidity of 0.55 pH units, and 0.33% DM, were observed. Total phenol content and antioxidant activity decrease to 5.57 mg GAE/g DM TPC, 22.20 μmol Fe2+/g DM FRAP and 8.12 μmol TE/g DM DPPH, during the storage (p&lt;0.05). Of fifteen phytochemical compounds, gallic, p-coumaric, trans-cinnamic acids, and epicatechin were in high abundance, with a notable decrease in epicatechin (38%). To the authors' knowledge, dihydrocaffeic and phloretic acids, daidzein, naringin, and naringenin were quantified in buckwheat flour for the first time. Easy adaptability to the environment, ability to attract various insects, speedy short-season growing plant for food, many nutritional and health benefits, gives buckwheat potential to be sustainable and biodiversity-friendly crops.

1,2-Dihydroisoquinolines are important compounds due to their biological and medicinal activities, and numerous approaches to their synthesis have been reported. In this study, a palladium-catalyzed cascade cyclization-coupling of trisubstituted allenamides containing a bromoaryl moiety with arylboronic acids is described. The reaction proceeds via intramolecular cyclization, followed by transmetallation with the arylboronic acid of the resulting allylpalladium intermediate. A variety of substituted 1,2-dihydroisoquinolines were concisely obtained using this methodology because the allenamides, as reaction substrates, were prepared from readily available propargylamines in one step.

Abstract: One of the most significant medical advancements of the 20th century was the discovery of antibiotics, which continue to play a vital tool in the treatment and prevention of diseases in humans and animals. However, the imprudent use of antibiotics in all fields of One-Health and concerns about antibiotic resistance among bacterial pathogens have raised interest in antibiotic use restrictions on a global scale. Despite the failure of conventional antimicrobial agents, only about 15 new antibiotics have been introduced clinically since year 2000 to date. Moreover, there have been reports of resistance to some of these new antibiotics. This has necessitated a need to search for an alternative strategy to combat antimicrobial resistant pathogens. Thus, this review compiles and evaluates the approaches—natural compounds, phage treatment, and nanomaterials—that are being used and/or suggested as the potential substitutes for conventional antibiotics. These strategies include those that focus on the enzymes or proteins, as well as the physiology and metabolism of resistant bacteria

A new frontier in solar thermal panel technology can be a high vacuum collector, thick enough to be equipped with solar concentrators based on non-imaging optics, such as the Compound Parabolic Concentrators (CPC). The high vacuum technology guarantees higher operating temperatures thanks to the enhanced thermal insulation, which leads to pay particular attention to the absorber radiative emission. In this paper by means of numerical simulations we compare the efficiency of a flat selective solar absorber under high vacuum to the efficiency of a CPC under high-vacuum collector.

Corn tassel is a by-product from hybrid corn seed production and a new source of phytochemicals including compounds with antioxidant activity. Four tassel development stages were evaluated in eight commercial corn varieties. Corn varieties and tassel developmental stages showed significant variations (P0.01) for all parameters. Total phenolic content and antioxidant activity were highest in field corn. KGW1, a purple waxy variety, had the highest anthocyanin content and carotenoid content at tassel development stages at 50% and 75% of pollen shed, whereas the tassel developmental stages at the 1st day of pollen shed and 50% of pollen shed had the highest of anthocyanin yield and carotenoid yield. The most suitable time for tassel harvest should be between the 1st day of pollen shed to 50% of pollen shed. Phytochemicals and antioxidants that are extracted from corn tassel can be used as a functional food supplement, natural pharmaceuticals and cosmetic products.

Compound parabolic concentrators are relevant systems used in solar thermal technology. With adequate tailoring, they can be used as an efficient and low-cost alternative in residential water applications. This work presents a simulation study using a ray tracing methodology. With this technique we simulate the interaction between solar rays and solar concentrator to quantify the amount of energy that impinges on the receiver at a particular time. Energy availability is evaluated in a comparison of two configurations: stationary at 21° throughout the year and multi position setup; tilted with respect to the horizontal depending on three seasonal positions: 0° for summer, 16° for spring / autumn and 32° for winter, with the objective of increasing the amount of available energy in each season. The fact that a tracking system can be dispensed with also represents an economical option for the proposed application. The results showed that at 21°, the proposed system works satisfactorily; however, by carrying out the selected angular adjustments, the overall energy availability increased by 22%, resulting in a more efficient option. The methodology developed herein proved to be a valuable tool for prototype design and performance evaluation.

The aim of this study is to characterize the compound extremes of rainfall and temperature in Côte d’Ivoire. For this purpose, we analyzed the outputs of fourteen (14) climate models from the CORDEX-Africa project. Results show an increase (approximately 4.3°C) of the surface temperature and a decrease (5,90 %) of the mean rainfall in the near (2036-2065) and far futures (2071-2100) over Côte d’Ivoire during January-February-March (JFM) period. The analysis of the compound extremes of wet/warm type highlights an increase in the frequency of this climatic hazard in the northern and central parts of the country during January-March (JFM) season in the near and far futures. The dry/warm mode will increase in the central and southern parts of the country during the near future and in the whole country during the far future. These increase in compound extremes could lead to an increase in droughts and natural disasters over the country and could have a negative impact on socio-economic activities, such as transportation and agricultural production. This work could provide decision support for political decision-makers in formulating future public policies for managing agricultural production, food security, and natural disasters.

Dengue (DENV) and Zika (ZIKV) virus continue to pose significant challenges globally due to their widespread prevalence and severe health implications. Given the absence of effective vaccines and specific therapeutics, targeting of the highly conserved NS5 RNA-dependent RNA polymerase (RdRp) domain has emerged as a promising strategy. However, limited efforts have been made to develop inhibitors for this crucial target. In this study, we employed an integrated in silico approach utilizing combinatorial chemistry, docking, molecular dynamics simulations, MM/GBSA, and ADMET studies to target the allosteric N-pocket of DENV3-RdRp and ZIKV-RdRp. Using this methodology, we designed lycorine analogs with natural S-enantiomers (LYCS) and R-enantiomers (LYCR) as potential inhibitors of non-structural protein 5 (NS5) in DENV3 and ZIKV. Notably, 12 lycorine analogs displayed a robust binding free energy (&lt;-9.00 kcal/mol), surpassing that of RdRp-Ribavirin (&lt;-7.00 kcal/mol) along with promising ADMET score predictions (&lt;4.00), of which (LYCR728-210, LYCS728-210, LYCR728-212, LYCS505-214) displayed binding properties to both DENV3 and ZIKV targets. This study highlights the potential of non-nucleoside lycorine-based analogs with different enantiomers that may present different or even completely opposite metabolic, toxicological, and pharmacological profiles as promising candidates for inhibiting NS5-RdRp in ZIKV and DENV3, paving the way for further exploration for the development of effective antiviral agents.

This study introduces an advanced dual-mode composite attitude control framework for reusable launch vehicles (RLVs), underpinned by an enhanced particle swarm optimization (PSO) algorithm. This innovative strategy is tailored to meet the stringent demands for precision and robust anti-interference capabilities across the entire flight envelope of RLVs. The research commences with the formulation of a comprehensive attitude dynamics model and diverse heterogeneous actuator representations, meticulously crafted to reflect the distinct phases of RLV flight. Building upon this foundation, a synergistic control paradigm is engineered, integrating PID and fuzzy PID controllers, complemented by a refined fitness evaluation function. The crux of the study is the application of an upgraded PSO algorithm to fine-tune the controllers' weighting coefficients, culminating in an optimized dual-mode composite attitude control system. A series of comparative simulation analyses are meticulously executed to appraise the system's responsiveness, stability, precision, and resilience to interference. The findings unequivocally substantiate the superior performance of the proposed control system, affirming its substantial contribution to the advancement of RLV attitude control.

Adult neurogenesis involves generation of functional neurons from neural progenitor cells, which have the potential to complement and restore damaged neurons and neural circuits. Therefore, the development of drugs that stimulate neurogenesis represents a promising strategy in stem cell therapy and neural regeneration, greatly facilitating the reconstruction of neural circuits in cases of neurodegeneration and brain injury. Our study reveals that compound A5, previously designed and synthesized by our team, exhibits remarkable neuritogenic activities, effectively inducing neurogenesis in neural stem/progenitor cells (NSPCs). Subsequently, transcriptome analysis using high-throughput Illumina RNA-seq technology was performed to further elucidate the underlying molecular mechanisms by which compound A5 promotes neurogenesis. Notably, comparative transcriptome analysis showed that the up-regulated genes were mainly associated with neurogenesis and the down-regulated genes were mainly concerned with cell cycle progression. Furthermore, we confirmed that compound A5 significantly affected the expression of transcription factors related to neurogenesis and cell cycle regulatory proteins. Collectively, these findings identify a new compound with neurogenic activity and may provide insights into drug discovery for neural repair and regeneration.

A general methodology for loan amortization under arbitrary discount functions is discussed. It is shown that it is always possible to uniquely define a scheme for constructing the loan amortization schedule with an arbitrary assigned discount function. It is also shown that even if the loan amortization is carried out from the sequence of principal payments and the sequence of accrued interest, the underlying discount function can be uniquely determined at the maturities corresponding to the installment payment dates. As a special case of the proposed approach, we derive the amortization method according to the law of simple interest.

Both auditory and vestibular primary afferent neurons can be activated by sound and vibration. This review relates differences between them to the different receptor/synaptic mechanisms of the two systems as shown by indicators of peripheral function – cochlear and vestibular compound action potentials (cCAPs and vCAPs) to click stimulation as recorded in animal studies. Sound and vibration sensitive type 1 receptors at the striola of the utricular macula are enveloped by the unique calyx afferent ending which has three modes of synaptic transmission. Glutamate is the transmitter for both cochlear and vestibular primary afferents, however blocking glutamate transmission has very little effect on vCAPs but greatly reduces cCAPs. We suggest that the ultrafast non-quantal synaptic mechanism called resistive coupling is the cause of the short latency vestibular afferent responses and related results – failure of transmitter blockade, masking, and temporal precision. This “ultrafast” non-quantal transmission is effectively electrical coupling dependent on the membrane potentials of the calyx and the type 1 receptor. The major clinical implication is that decreasing stimulus rise-time increases vCAP response, corresponding to the increased VEMP response in human subjects . Short rise-times are optimum in human clinical VEMP testing, whereas long rise-times are mandatory for audiometric threshold testing.

High-grade gliomas present a significant challenge in neuro-oncology because of their aggressive nature and resistance to current therapies. Boron neutron capture therapy (BNCT) is a potential treatment method; however, the boron carrier compounds used — such as 4-borono-L-phenylalanine (L-BPA) — have limitations. This study evaluated the use of boron-conjugated 4-iodophenylbutanamide (BC-IP), a novel boron compound in BNCT, for the treatment of glioma. Using in vitro drug exposure experiments and in vivo studies, we compared BC-IP and BPA, with a focus on boron uptake and retention characteristics. The results showed that although BC-IP had a lower boron uptake than BPA, it exhibited superior retention. Furthermore, despite lower boron accumulation in tumors, BC-IP showed significant survival improvement in glioma-bearing rats compared to controls. These results suggest that BC-IP, with its unique properties, may be an alternative boron carrier for BNCT. Further research is required to optimize this potential treatment modality, which could significantly contribute to advancing the treatment of high-grade gliomas.

This work is the first scientific study on the development of the composition and technology of a new antioxidant agent based on a combination of extracts of tree medicinal plants and the study of the technological parameters of a dry extract. Further draw up technological regulations for their production and their introduction into production. This study aims to the antioxidant activity of dry extract "Antioxim" was determined. In order to create this herbal collection of plant, first of all, to study the technological parameters of raw materials, such as mass size, porosity, dispersibility, free volume of layers of raw materials, water absorption coefficient of extractives, and technological process efficiency to study the effect of parameters, developed at the Department of "Industrial Technology of Medicines" of the Tashkent Pharmaceutical Institute:

Natural products (NPs) are a rich source of structurally novel molecules, and the chemical space they encompass is far from being fully explored. Over history, NPs have represented a significant source of bioactive molecules and have served as a source of inspiration for developing many drugs on the market. On the other hand, computer-aided drug design (CADD) has contributed to drug discovery research, mitigating costs and time. In this sense, compound databases represent a fundamental element for the CADD. This work reviews the progress toward developing compound databases of natural origin, particularly databases developed in Latin America, and their practical applications in the drug discovery area. We also survey the computational methods, emphasizing chemoinformatic approaches to profile natural product databases.

Volatile compounds, abundant in breath, can be used to accurately diagnose and monitor a range of medical conditions. This offers a non-invasive, low-cost approach with screening applications; however, uptake of this diagnostic approach has been limited by conflicting published outcomes. Most published reports rely on large scale screening of the public, at single time points and without reference to ambient air. Here, we present a novel approach to volatile sampling from cellular headspace and mouse breath that incorporates multi-time point analysis and ambient air subtraction revealing compound flux as an effective proxy of active metabolism. This approach to investigating breath volatiles offers a new avenue for disease biomarker discovery and diagnosis. Using gas chromatography mass spectrometry (GC/MS), we focus on low molecular weight, metabolic substrate/by-product compounds and demonstrate that this non-invasive technique is sensitive (reproducible at ~1 µg cellular protein, or ~500,000 cells) and capable of precisely determining cell type, status and treatment. Isolated cellular models represent components of larger mammalian systems and we show that stress- and pathology-indicative compounds are detectable in mice, supporting further investigation using this methodology as a tool to identify volatile targets in human patients.

The processing of alkanes (the main components of natural gas) for obtaining of industrially important chemical products is one of the most urgent environmental problems, because the major share of raw materials are burned in torches. Therefore, the main goal of the work is the development of catalysts and conditions for obtaining of important petrochemical products from light alkanes. For the preparation of catalysts, Mo, Cr and Ga oxide catalysts as well as catalysts based on heteropoly compounds, supported on natural materials were used. The catalysts were prepared by the capillary impregnation method and used in oxidative conversion in a flowing unit while varying the process conditions. It has been determined that 5 and 10% MoCrGa catalysts are optimal for obtaining of liquid and gaseous products, and 1% catalyst is more favorable for the synthesis of gaseous products. Supported catalysts from heteropoly acid Н₃PW₁₂O₄₀ are highly active in oxidative dehydrogenation and cracking processes, which are concurrent. High activity is caused by dispersity of catalysts, formation of crystal hydrates and amorphous phase of heteropoly acid in a condition of interaction with carrier. Maximum yield of C₂H₄ - 35.2% at 973 K, C₃H₆ – 20.0% and C₄H₈ – 14.3% at 773 К were observed.

In order to enhance the efficiency and combined performances of nitriding layer, aluminum-modified plasma nitriding (Al-PN) was developed in this research by adding some FeAl particles around the samples during plasma nitriding (PN) for 42CrMo steel. The results show that the efficiency is dramatically enhanced almost 6 times comparing with traditional PN, with the effective hardening layer increasing from 224 μm to 1246 μm at 520℃/4h. More importantly, the compound layer increased just a little bit from 11.64 μm to 14.32 μm, which remarkably reduces the ratio of the compound layer thickness to effective hardening layer thickness, thus being quite beneficial to decrease the brittleness level, making the brittleness level decreasing from Level 4 to Level 1. Meanwhile, ultra-high surface hardness and excellent wear behaviors are obtained by aluminum-modified plasma nitriding (Al-PN) due to the formation of dispersed strengthening phased of AlN and FexAl in the nitriding layer, with the surface hardness increasing from 755 HV0.025 to 1251 HV0.025, wear rate decreasing from 8.15 x10-5g N-1 m-1 to 4.07 x10-5g N-1 m-1. In other words, comparing with PN, the wear resistance has been almost doubled by Al-PN. Therefore, the research can provide comprehensive insights into the surface characteristics and combined performances of the aluminum-modified plasma nitriding layer.

Multiple sources influence air quality and regional climate in complicated atmospheric emission situations like urban agglomerations. To resolve pollution plumes and source influences in polluted areas, a comprehensive chemical fingerprinting of sources utilizing non-methane hydrocarbons (NMHCs) and the identification of acceptable tracer molecules and emission ratios is required, in contrast to pristine locations, where reliance on a single or a few chemical tracers is frequently sufficient. We have characterized the prevalence of NMHCs fingerprints in the urban areas and quantified the correlation of windspeed with the concentration of these pollutants. eNose sensors and Air quality management stations provide the data to identify the emission sources of such pollutants. Based on our analysis, the average NMHC concentration in 2021 has been recorded 0.424 ppm at point 1 AQMS whereas at point 2 AQMS it was 0.256 ppm. Such outcomes could be attributed to the proximity of emissions sources, the direction and speed of the wind, or both. Moreover, traffic can be a major contributor to pollution levels in any urban area. More research based on a larger dataset is required before definitive conclusions can be drawn, and viable solutions can be proposed.

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a predominant cause of mortality, especially in low- and middle-income nations. Recently antimicrobial peptides were discovered that at low concentrations could stimulate the growth of M. tuberculosis (hormetic response). In this study, such a peptide was used to investigate the effects on the time to positivity (TTP). A systematic substitution analysis of peptide 14D was synthesized using Spot synthesis technology, resulting in 171 novel peptides. Our findings revealed a spectrum of interactions, with some peptides accelerating M. tuberculosis growth, potentially aiding in faster diagnostics, while others exhibited inhibitory effects. Notably, peptide NH2-wkivfiwrr-CONH2 significantly reduced the TTP by 25 hours compared to the wild-type peptide 14D, highlighting its potential in improving TB diagnostics by culture. Several peptides demonstrated potent antimycobacterial activity, with a minimum inhibitory concentration (MIC) of 20 µg/mL against H37Rv and a multidrug-resistant M. tuberculosis strain. Additionally, a reduction in the formation of cord-like structures was observed, which is indicative of reduced virulence and transmission potential. This study underscores the multifaceted roles of antimicrobial peptides in TB management, from enhancing diagnostic efficiency to offering therapeutic avenues against M. tuberculosis.

In tire tread applications, achieving enhanced abrasion resistance, wet grip, and rolling resistance is crucial for optimizing overall performance. To realize improvements in these attributes for silica-filled tire tread compound, it becomes imperative to improve dispersity of silica filler with investigating the effect of each component in tire tread compound. In this work, we study the effect of styrene content within solution styrene butadiene rubber (SSBR) on the properties of tire tread compounds. A higher styrene segment within SSBR contributes to increased silica dispersion and crosslink density. Thus, tire tread compounds featuring SSBR with increased styrene content not only improve physical and mechanical properties but also enhance major characteristics tailored for tire tread applications. These findings provide valuable insights into advancing the reinforced performance of tire tread compounds through the strategic utilization of SSBR enriched in styrene content.

Sedimentation processes have negative socioeconomic and environmental consequences, ranging from eutrophication phenomena, loss of water quality in surface water bodies, effects on the potential for hydroelectric generation, etc. Frequently, anthropic activity is the main cause that enhances these processes through changes in land use that can lead to landscape modifications. Therefore, it is relevant to evaluate this phenomenon and to be able to discriminate the influence of different land uses on the contributions to sediment loads at different scales. The novel Compound Specific Stable Isotopes technique allows the evaluation of sediment inputs associated with different land use changes in a study region. In the present work this technique was used in the Alhajuela Lake sub-basin, within the Panama Canal Watershed. The contribution levels of three (3) representative land uses (forest, pasture and sediment) in the study area were evaluated for the sediments present in sixteen (16) selected mixing points. The main contributions of the sources to the sediments present in the main rivers and tributaries flowing into Alhajuela Lake, in the sub-basin of the same name, were identified. The results obtained are consistent with observations and measurements of sedimentation in the study area.

Low pressure fluid transport (1) applications often require low and precise volumetric flow rates (2) including low leakage to reduce additional costly and complex sensors. A peristaltic pump de-sign (3) was realized, with the fluid’s flexible transport channel formed by a solid cavity and the wobbling plate comprising a rigid and a soft layer (4). In operation, the wobbling plate is driven externally by an electric motor, hence, the soft layer is contracted and unloaded (5) during pump-cycles transporting fluid from low to high pressure sides. A thorough characterization of the pump system is required to design and dimension the components of the peristaltic pump. To capture all these parameters and their dependencies on various operation-states, often complex and long-lasting dynamic 3D FE-simulations are required. We present, here, a holistic design methodology (6) including analytical as well as numerical calculations, and experimental valida-tions for a peristaltic pump with certain specifications of flow-rate range, maximum pressures, and temperatures. An experimental material selection process is established and material data of candidate materials (7) (liquid silicone rubber, acrylonitrile rubber, thermoplastic-elastomer) are directly applied to predict the required drive torque. For the prediction, a semi-physical, analyti-cal model was derived and validated by characterizing the pump prototype.

Elephant dung coffee (Black Ivory Coffee) is a special Thai coffee produced from Arabica coffee cherries consumed by Asian elephants and collected from their feces. In this work, elephant dung coffee and controls were analyzed using static headspace gas chromatography hyphenated with mass spectrometry (SHS GC–MS), and chemometric approaches were applied for multivariate analysis and the selection of marker compounds that are characteristic of the coffee. Seventy-eight volatile compounds belonging to 13 chemical classes were tentatively identified, including 6 alcohols, 5 aldehydes, one carboxylic acid, 3 esters, 17 furans, one furanone, 13 ketones, 2 oxazoles, 4 phenolic compounds, 14 pyrazines, one pyridine, 8 pyrroles and 3 sulfur-containing compounds. Moreover, four potential discriminant markers of elephant dung coffee, including 3-methyl-1-butanol, 2-methyl-1-butanol, 2-furfurylfuran and 3-penten-2-one were established. The proposed method may be useful for elephant dung coffee authentication and quality control.

Vitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder, caused by pathogenic variants in the CYP27B1 gene, typically characterized by growth failure, rickets, leg bowing, fracture, seizures, hyperparathyroidism, hypocalcemia, high alkaline phosphatase, high or normal 25(OH)D3, and low 1,25(OH)2D3. We studied two siblings in a Mexican family with an atypical form of VDDR1A. In addition to the typical features of VDDR1A, the proband showed cafe au lait spots, small teeth and grayish sclera, with hypophosphatemia, normocalcemia and normal 25(OH)D3, the proband´s brother showed grayish sclera. Proband underwent Next Generation Sequencing. Sanger sequencing was performed in the proband, his brother, the parents and 100 healthy controls for validation of detected variant. Both brothers presented a recurrent variant NM_000785.3; c.1319_1325dupCCCACCC and a novel nonsense variant NM_000785.3; c.227G>A in the CYP27B1 gene. Calcitriol treatment had better response in proband´s younger brother. We describe the first Mexican family with an atypical form of VDDR1A associated with novel nonsense variant, the results contribute to the phenotypic spectrum and increases the pool of pathogenic variants in CYP27B1. Data suggesting that nonsense-truncating variants play a significant role in the severity of VDDR1A.

Arsenic trioxide (ATO) has been shown to inhibit pancreatic cell growth in vitro and to promote the inhibitory effects of gemcitabine on pancreatic cancer in vivo. However, the high toxicity of ATO associated with the required high doses and indiscriminate targeting has limited its clinical application. This study aimed to determine whether coupling arsenic to a tumor homing peptide would increase the inhibitory potency against pancreatic cancer cells. The effects of this peptide-linked arsenic compound and ATO on pancreatic cancer growth were tested in vitro and in a mouse model. The data demonstrated that the peptide-linked arsenic compound inhibited pancreatic cancer cell growth more potently with IC50 values 10 times lower than ATO. Like ATO, the peptide-linked compound induced cell death and cell cycle arrest. More importantly, the peptide-linked arsenic compound inhibited pancreatic cancer growth in mice and enhanced the inhibitory effect of gemcitabine on pancreatic cancer growth at 2 times lower molar concentration than ATO. These results indicate that the peptide-linked arsenic compound inhibited pancreatic cancer more potently than ATO and suggest a potential clinical use for the combination of gemcitabine with the peptide-linked arsenic compound for the treatment of pancreatic cancer.

Extreme climates such as droughts and hot extremes, may result in marked damage to crop yields and threaten regional and global food security. Maize is a major grain crop in Liaoning Province, severely affected by drought and hot events. The objective of this study is to advance an approach to estimate the risk of crop yield reduction under the compound dry-hot events (CDHE) in Liaoning Province. Results show that the ratio of stations experiencing compound dry-hot events during the twelfth leaf and maturity stage tended to increase on the time scale. On a spatial scale, the frequency of compound dry-hot events in central Liaoning Province was relatively low during the whole and various reproductive periods of maize. In addition to the twelfth leaf, western Liaoning Province is prone to compound dry-hot events. The high-risk area for the occurrence of the compound dry-hot events in maize is Chaoyang City, located in the western part of Liaoning Province, and the cities in the low-risk area account for about 64.3% of the total number of cities in Liaoning Province, mainly in the central and northern parts of Liaoning Province. Generally, this study emphasizes focusing on the impacts of compound dry-hot events on agricultural production and provides an index to assess the risk of compound dry-hot events on maize production.

Repeated air pollution exposure is one of the major threats to skin health. Air pollution causes skin damage and accelerates skin ageing mainly through oxidative stress mechanisms. Since it is difficult to minimize skin exposure from air pollutants, especially in urban areas, strategies to protect the skin are needed. On the other hand, plant phenolic compounds have been found to be effective in attenuating cellular oxidative stress and inflammation induced by different air pollutants. Therefore, we conducted a 12-week randomized, placebo-controlled, double blind study to assess the efficacy of a polyphenol-enriched dietary supplement (comprised of olive leaf, lemon verbena, rosemary and Sophora japonica extracts) in reducing pollution-induced oxidative stress and in improving different skin parameters related to skin ageing of Caucasian and Asian volunteers living in a polluted urban European area (Milan). One hundred healthy women were recruited and randomized in the placebo or in the test dietary supplement treatment arms. To assess the efficacy of the dietary supplement, the total antioxidant capacity on saliva (FRAP) was determined, as well as the oxidative damage on skin (lipoperoxides content), the skin moisture (corneometry), the trans-epidermal water loss (Tewameter), the skin radiance and the skin colour, (spectrophotometry), the skin elasticity (cutometry), the skin sebum content (sebumeter), and the skin roughness (image analysis). As a result, both inter-group and intra-group analysis proved that the dietary supplement improved all clinical and biochemical monitored parameters, in both Caucasian and Asian individuals. In conclusion, the results of the study indicate a reduced oxidative stress-induced skin damage in both Asian and Caucasian women living in a polluted urban area.

Traditional flood hazard analyses often rely on univariate probability distributions; however, in many coastal catchments, flooding is the result of complex hydrodynamic interactions between multiple drivers. For example, synoptic meteorological conditions can produce considerable rainfall-runoff, while also generating wind-driven elevated sea levels. When these drivers interact in space and time, they can exacerbate flood impacts; this phenomenon is known as compound flooding. In this paper, we build a Bayesian Network based on Gaussian copulas to generate the equivalent of 500 years of daily stochastic boundary conditions for a coastal watershed in Southeast Texas. In doing so, we overcome many of the limitations of conventional univariate approaches and are able to probabilistically represent compound floods caused by riverine and coastal interactions. We calculate the resulting water levels using a 1D steady-state hydraulic model and find that flood stages in the catchment are strongly affected by backwater effects from tributary inflows and downstream water levels. By comparing with a bathtub modeling approach, we show that simplifying the multivariate dependence between flood drivers can lead to an underestimation of flood impacts, highlighting that accounting for multivariate dependence is critical for the accurate representation of flood risk in coastal catchments prone to compound events.

The prototype misfit layer compound (SnS)1.17NbS2 consists of alternatively a metallic triatomic NbS2 layer in which Nb atoms are sandwiched by S atoms and an insulating SnS double-layer of NaCl-type structure. Here we investigate the effect of lattice misfit on the stability and chemical bonding in the misfit layer compound using a first-principles density-functional theory approach. The calculations show that for the (SnS)1+xNbS2 approximants, the most stable one has x = 0.167, close to the experimental observations. Charge analysis finds a moderate charge transfer from the SnS to NbS2. Sn or S vacancies in the SnS part affect the electronic properties and interlayer interactions. The obtained information here helps understand the mechanism of formation and stability of the misfit layer compounds and ferecrystals, and further to design of novel multilayer compounds and emerging van der Waals heterostructures.

Dysregulation of the arsenal of cells, growth factors, cytokines, proteases, and proteins involved in wound healing (WH), could delay the healing process. Plants and plant-derived molecules (PDMs) have been used as medicines for skin wounds. This study aimed to select and evaluate the pro-healing capacity of PMDs. Thirty-three PDMs and 10 therapeutic targets (TTs) were chosen for molecular docking and PDMs: aristolochic acid (AA), α-copaene, selinenes, β-caryophyllene (BC), and BCoxide, and TTs: metalloproteinase (MMP) 3, MMP13, and tumor necrosis factor (TNF α) for molecular dynamics. The bests inhibitor was AA, but because of its toxicity, BC and BCoxide were chosen for evaluation in HaCat cells and BALB/c mice excisional model. Both compounds were not toxic, and higher percentages of lesion area closure (LAC) were induced by BC treatment (p<0.05). All mice healed; however, an initial delay of LAC was induced by 0.05, 0.1% BCoxide, 0.1% BC, and allantoin. At the end of treatment, lower numbers of mast cells, level of cellular infiltrates (except 1% BCoxide and 0.05, 0.5%BC), epidermal thickness tendency (except 0.1, 0.5% BCoxide), and higher values of SC-thickness, and collagen fibers only by 0.5% BC treatment compared with untreated control (p<0.05) were observed. Our results show that BC is a promising multitarget candidate for wound healing treatment and optimization campaigns.

Initial water content significantly affects the efficiency of soil stabilization. In this study, the effects of initial water content on the compressibility, strength, microstructure and composition of a lean clay soil stabilized by compound calcium-based stabilizer were investigated by static compaction test, unconfined compression test, optical microscope observations, environment scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray diffraction spectroscopy. The results indicate that as the initial water content increases in the range studied, both the compaction energy and the maximum compaction force decrease linearly and there are less soil aggregates or agglomerations, and smaller proportion of large pores in the compacted mixture structure. In addition, for specimens cured with or without external water supply and under different compaction degrees, the variation law of the unconfined compressive strength with initial water content is different and the highest strength value is obtained at various initial water contents. With the increase of initial water content, the percentage of oxygen element tends to increase in the reaction products of the calcium-based stabilizer, whereas the crystalline mineral of the soil did not change obviously.

The problem of effective immobilization of liquid radioactive waste (LRW) is key to the successful development of nuclear energy. The possibility of using magnesium potassium phosphate (MKP) compound for LRW immobilization on the example of nitric acid solutions containing actinides and rare earth elements (REE), including high level waste (HLW) surrogate solution is considered in the research work. Under the study of phase composition and structure of the MKP compounds obtained by the XRD and SEM methods, it was established that the compounds are composed of crystalline phases - analogues of natural phosphate minerals (struvite, metaankoleite). The hydrolytic stability of the compounds was determined according to the semi-dynamic test GOST R 52126-2003. Low leaching rates of radionuclides from the compound are established, including a differential leaching rate of ²³⁹Pu and ²⁴¹Am - 3.5 × 10^-7 and 5.3 × 10^-7 g/(cm²∙day). As a result of the research work it was concluded that the MKP compound is promising for LRW immobilization and can become an alternative material combining the advantages of easy implementation of the technology like cementation and the high physical and chemical stability corresponding to a glass-like compound.

Diamidophosphate has been identified as a possible prebiotic compound used in the precursor membranes of the first ‘life’. Compounds such as these will be helpful in developing novel biomimetic approaches in synthetic chemistry. Thermochemical data for this type of compounds are not available. Hess’ law and estimates from calorimetric measurements used by Wakefield in the 1970s for other amido phosphates have been used to estimate the thermochemical values for the diamido and monoamido-phosphoric acid. Enthalpy of formation at 298.15 ^oC is calculated as – 821.9 kJ/mol and the free energy of formation calculated as -813.5 kJ/mol for the diamidophosphoric acid. The calculated enthalpy of formation of monoamidic phosphoric acid is -1117.1 kJ/mol and its free energy of formation is - -1105 kJ/mol.

Carbon fiber-reinforced polymer (CFRP), noted for its outstanding properties including high specific strength and superior fatigue resistance, is increasingly employed in aerospace and other demanding applications. This study investigates the interactions between CFRP composites and high-energy lasers (HEL), with continuous wave laser powers reaching up to 120 kW. A novel automated sample exchange system, operated by a robotic arm, minimizes human exposure while enabling a sequence of targeted laser tests. High-speed imaging captures the rapid expansion of a plume consisting of hot gases and dust particles during the experiment. The research significantly advances empirical models by systematically examining the relationship between laser power, perforation times, and ablation rates. It demonstrates scalable predictions for the effects of high-energy laser radiation. Detailed examination of the damaged samples, both visually and via micro-focused computed X-ray tomography, offers insights into heat distribution and ablation dynamics, highlighting the anisotropic thermal properties of CFRP. Compression-after-impact (CAI) tests further assess the residual strength of the irradiated samples, enhancing the understanding of CFRP’s structural integrity post-irradiation. Collectively, these tests improve the knowledge of the thermal and mechanical behavior of CFRP under extreme irradiation conditions. The findings not only contribute to predictive modeling of CFRP's response to laser irradiation but also enhance the scalability of these models to higher laser powers, providing robust tools for predicting material behavior in high-performance settings.

Comparisons of power flows and efficiencies in two structurally quite similar cylindrical series-parallel planetary gear systems (PGSs) were performed in three separate parts of this paper. Each of these single degree of freedom (DoF) systems consists of three different 2KH subsystems connected in series-parallel. The main goal was to prove that apart from complex, structurally and dynamically coupled PGSs, there are also complex and only structurally coupled PGSs, in which the phenomenon of power flow circulation inside closed loops does not occur. Such a half-coupled type of PGS is herein called pseudo-coupled. Therefore, Part I discusses in detail the geometry, kinematics and statics of coupled PGSs in order to determine power flow paths. A comparison of the directions of power flow in both types of PGSs can be made in Part II after determining the power flow paths in the second planetary gear in a similar way. The directions of power flow in both types of PGSs were determined in a relatively simple way, thanks to the distinction between active and passive torques and thus active and passive shafts of individual subsystems. The efficiency comparison made in Part III will show whether power circulation has an influence on the efficiency value, at least in these two types of PGSs.

The solid particle erosion at room and elevated temperatures of pure and filled hot-curing epoxy resin on anhydride hardener was experimentally tested using accelerated method on special bench. Micro-sized dispersed industrial wastes were used as fillers: fly-ash from a power plant and spent filling material from a copper mining and processing plant. The results showed that the unfilled resin wear significantly decreases with increasing temperature, while the dependence on the temperature of the wear intensity at an impingement angle of 45o is linear inversely proportional, and at an angle of 90o non-linear. The decrease in wear intensity is probably due to an increase in elasticity (an increase in the fracture strain limit) because of heating. Solid particle erosion of the examined filled epoxy compounds is considerably higher than that of unfilled compounds at impingement angles of 90o and 45o. Filled compounds showed ambiguous dependences of intensity of wear from temperature (especially at an angle of attack 45o), probably, character of dependence is defined by a filler share and the structural features of the samples caused by distribution of particles of the filler. Intensity of wear of the considered compounds at impingement angles 90o and 45o has high direct correlation with density and the modulus of elasticity (i.e., increases with their increase), and low correlation with bending strength of the considered materials. The data set for determining the correlation between mechanical properties and wear included characteristics due to both compound filling and test temperature.

The interaction between oceanographic, meteorological, and hydrological factors can result in an extreme flooding scenario in the low-lying coastal area, called compound flooding (CF) events. For instance, rainfall and storm surge (or high river discharge) can be driven by the same meteorological, tropical or extra-tropical cyclones, resulting in a CF phenomenon. The trivariate distributional framework can significantly explain compound events' statistical behaviour reducing the associated high-impact flood risk. Resolving heterogenous dependency of the multidimensional CF events by incorporating traditional 3-D symmetric or fully nested Archimedean copula is quite complex. The main challenge is to preserve all lower-level dependencies. An approach based on decomposing the full multivariate density into simple local building blocks via conditional independence called vine or pair-copulas is a much more comprehensive way of approximating the trivariate flood dependence structure. In this study, a parametric vine copula of a drawable (D-vine) structure is introduced in the trivariate modelling of flooding events with 46 years of observations of the west Coast of Canada. This trivariate framework searches dependency by combining the joint impact of annual maximum 24-hr rainfall and the highest storm surge and river discharge observed within the time ±1 day of the highest rainfall event. The D-vine structures are constructed in three alternative ways by permutation of the conditioning variables. The most appropriate D-vine structure is selected using the fitness test statistics and estimating trivariate joint and conditional joint return periods. The investigation confirms that the D-vine copula can effectively define the compound phenomenon's dependency. The failure probability (FP) method is also adopted in assessing the trivariate hydrologic risk. It is observed that hydrologic events defined in the trivariate case produce higher FP than in the bivariate (or univariate) case. It is also concluded that hydrologic risk increases (i) with an increase in the service design life of the hydraulic facilities and (ii) with a decrease in return periods.

Aging is a complex and inevitable biological process characterized by a gradual decline in physiological function, including increased oxidative stress, chronic inflammation, and mitochondrial dysfunction. While aging is a natural part of life, it is often accompanied by various disorders collectively known as age-related diseases (ARDs) or aging disorders. These include neurodegenerative diseases like Parkinson’s (PD), cardiovascular diseases, diabetes, osteoporosis, and frailty, among others. As the global population ages, the prevalence of ARDs such as PD and frailty is rising, necessitating innovative approaches to enhance healthy aging. Nutraceuticals are natural bioactive compounds in foods that offer health benefits beyond essential nutrition, which is pivotal in preventing and managing aging-related disorders. Nutraceuticals, with their antioxidant, anti-inflammatory, and neuroprotective properties, offer promising strategies to counteract these processes and promote healthy aging. This review highlights the potential of nutraceuticals as valuable adjuncts in managing PD and frailty, two conditions intricately linked to ARD. By examining the differential impacts of these bioactive compounds on the underlying mechanisms of each condition, this study underscores the promise of nutraceuticals in promoting healthy aging. The review aims to inform future research and clinical strategies by advocating for developing novel bioactive compounds, using advanced delivery technologies, and integrating personalized approaches based on genetic and epigenetic profiles. These efforts will pave the way for more precise, effective, and individualized interventions, ultimately extending health span and preventing ARD.

Global warming is increasing the frequency and intensity of compound drought-heat events (CDHEs), potentially leading to larger and more extreme fire seasons in mesic forests. Wildfire activity in subtropical China, under the influence of monsoonal rainfall, was historically limited to dry winters and rare in rainy summers. Here we seek to test that this area is on the brink of a major change in its fire regime characterized by larger fire seasons, extending into the summer, leading to increases in burned area. We analyze fire activity in Chongqing Municipality (46,890 km2), an important area in subtropical China hosting the Three Gorges Reservoir Area. We observed significant increases in summer forest fires under anomalous dry-hot summer conditions, where total burned area was 3-6 higher than the historical annual mean (largely confined to the winter season). Vapor pressure deficit, an indicator of hot and dry conditions, was a strong predictor of fire activity, with major wildfires occurring on days where VPD was higher than 3.5kPa. Results indicate that major wildfire activity may occur in the area as a result of climate change, unless strong fire prevention policies are implemented.

For each $t\in(-1,1)$, exact values of the least upper bounds $$ H(t)=\sup_{\E X=t,\,\E X^2=1} \frac{\E\abs{X}^3}{\E \abs{X-t}^3},\quad \sup_{\E X=t,\,\E X^2=1} \frac{L_1(X)}{L_1(X-t)} $$ are obtained, where $L_1(X)=\E|X|^3/(\E X^2)^{3/2}$ is the non-cental Lyapunov ratio. It is demonstrated that these values are attained only at two-point distributions. As a corollary, S.\,Shorgin's conjecture is proved that states that the exact value is $$ \sup\frac{L_1(X)}{L_1(X-\E X)}= \frac{\sqrt{17 + 7\sqrt7}}{4} = 1.4899\ldots, $$ where the supremum is taken over all non-degenerate distributions of the random variable $X$ with the finite third moment. Also, in terms of the central Lyapunov ratio $L_1(X-\E X)$, an analog of the Berry--Esseen inequality is proved for Poisson random sums of independent identically distributed random variables with the constant $$ 0.3031\cdot H\left(\frac{\E X}{\sqrt{\E X^2}}\right) \left(1-\frac{(\E X)^2}{\E X^2}\right)^{3/2} \le 0.3031\cdot \frac{\sqrt{17 + 7\sqrt7}}{4}<0.4517.$$ where $\Law(X)$ is the common distribution of the summands.

The paper deals with the Compound Inverse Rayleigh distribution, shown to constitute a proper model for the characterization of the probability distribution of extreme values of wind-speed, a topic which is gaining growing interest in the field of renewable generation assessment, both in view of wind power production evaluation and the wind-tower mechanical reliability and safety. The first part of the paper illustrates such model starting from its origin as a generalization of the Inverse Rayleigh model - already proven to be a valid model for extreme wind-speeds - by means of a continuous mixture generated by a Gamma distribution on the scale parameter, which gives rise to its name. Moreover, its validity to interpret different field data is illustrated, also by means of numerous numerical examples based upon real wind speed measurements. Then, a novel Bayes approach for the estimation of such extreme wind-speed model is proposed. The method relies upon the assessment of prior information in a practical way, that should be easily available to system engineers. In practice, the method allows to express one’s prior beliefs both in terms of parameters, as customary, and/or in terms of probabilities. The results of a large set of numerical simulations – using typical values of wind-speed parameters - are reported to illustrate the efficiency and the accuracy of the proposed method. The validity of the approach is also verified in terms of its robustness with respect to significant differences compared to the assumed prior information.

Studies on the characteristics of hazardous air pollutants (HAPs) in the emissions of medium-duty diesel trucks are significantly insufficient compared to that on heavy-duty trucks. This study investigates the characteristics of regulated pollutants and HAPs such as volatile organic compounds (VOCs), aldehydes, and polycyclic aromatic hydrocarbons (PAHs), and estimates non-methane hydrocarbon (NMHC) speciation in the emissions of medium-duty diesel trucks. Ten medium-duty diesel trucks conforming to Euros 5 and 6 were tested for worldwide harmonized light duty driving test cycle (WLTC), new European driving cycle (NEDC), constant volume sampler (CVS)-75, and National Institute of Environmental Research (NIER)-9 using a chassis dynamometer. CO and NMHC emissions were the highest in the NEDC because of its longer low-speed driving time. NOx emissions were the highest in WLTC owing to the influence of thermal NOx in the high-speed phase. Alkanes dominated non-methane volatile compound (NMVOC) emissions owing to the low reaction of the diesel oxidation catalyst. After-treatment system, driving, and engine conditions influenced the individual components of NMVOC emissions. Formaldehyde emissions were the highest among aldehydes irrespective of driving cycles. By sampling the particle-phase of PAHs, we detected benzo(k)fluoranthene and benzo(a)pyrene and estimated the concentrations of the gas-phase PAHs with models to obtain the total PAH concentrations. The toxic equivalency quantities of benzo(k)fluoranthene and benzo(a)pyrene from NIER-9 (cold) for both Euro 5 and Euro 6 vehicles were more than five times higher than that of NIER (hot) and NEDC. In the case of NMHC speciation, formaldehyde emissions were the highest in all the driving cycles. Formaldehyde and benzene must be controlled in the emissions of medium-duty diesel trucks to reduce their health threats. The results of this study will aid in establishing a national emission inventory system for HAPs of mobile sources in Korea.

This study attempts to classify compound words on the basis of Cognitive Linguistics and compares their usage trends using Computational Linguistics. Using Noam Chomsky’s concept of deep and surface structures of a sentence, Lees treated compound words, not as separate units but as a kind of embedded sentences and hinted for possible presence of deep and surface structures in compound words, which this study tries to investigate. Then on the basis of the Idealized Cognitive Model proposed by Lakoff and Fauconnier, compound words have been classified into transparent, opaque and counterintuitive compound words. Using Google Books Corpus, this study also compares their usage trends. This is done using usage frequency, defined in this work, which is analogous to productivity for affixed words calculated by G.E.Booij. Each class of compound word formed on the basis of ICM is found to have different usage frequency. The possible reasons for this are discussed.

Maria Valtorta (MV) (1897–1961) – an Italian mystic who claimed to have visions of Jesus’s life – describes Jesus’ crucifixion with many details from which significant data can be retrieved. My investigation based on these data and the topography of northwest Jerusalem in the I century AD, shows that Jesus’ crucifixion place, Golgotha (the “skull”), is neither at the Holy Sepulchre nor in the Garden Tomb area. The paved road to Golgotha she accurately describes arrives at its top with the minimum mean route gradient; its half way defines two distinct tracts with same height and same walking time but different mean route gradient; at half way Jesus is allowed to walk to the top in a spiral country road less steep than the second tract. The paved road leads to a place where few years after Jesus’ crucifixion the Psephinus Tower, described by Flavius Josephus, was erected, in the area known today as the Russian Compound. In conclusion, the Golgotha reveiled by MV’s writings was located at the same site of the Psephinus Tower.

Manipulating autophagy is a promising strategy for treating cancer as several autophagy inhibitors shown to induce autophagic cell death. One of these, autophagonizer (APZ), induces apoptosis-independent cell death by binding an unknown target via an unknown mechanism. To identify APZ targets we used a label-free drug affinity responsive target stability (DARTS) approach with a liquid chromatography/tandem mass spectrometry (LC-MS/MS) readout. Of 35 protein interactors, we identified Hsp70 as a key target protein of unmodified APZ in autophagy. Either APZ treatment or Hsp70 inhibition attenuates integrity of lysosomes, which leads to autophagic cell death exhibiting an excellent synergism with a clinical drug, temozolomide, in vitro, in vivo, and orthotropic glioma xenograft model. These findings demonstrate the potential of APZ to induce autophagic cell death and its development to combinational chemotherapeutic agent for glioma treatment. Collectively, our study demonstrated that APZ, a new autophagy inhibitor, can be used as a potent antitumor drug candidate to get over unassailable glioma and revealed a novel function of Hsp70 in lysosomal integrity regulation of autophagy.

Despite effective vaccines, yellow fever outbreaks persist, increasing the urgency to find antivirals for patient treatment. This study aimed to discover compounds with potential antiviral properties against the wild-type yellow fever virus (wt-YFV) in Hippeastrum puniceum, of the Amaryllidaceae family, through bioassay-guided fractionation of the crude bulb extract using ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution ESI-QTOF mass spectrometry and subsequent analysis of the pharmacokinetic and toxicological properties (ADMET) of the annotated compounds. In the active fractions against wt-YFV, six alkaloids were proposed such as bulbisine, cathinone, trigonelline, tetrahydroharman-3-carboxylic acid, and 2,7-dimethoxyhomolycorine (or 3-O-acetylnarcissidine). Co-occurring in these fractions were the amino acids arginine, asparagine, tryptophan, and glutamic acid. In silico ADMET analysis of the alkaloids predicted good absorption, distribution, excretion, favorable metabolization profiles, and non-mutagenic toxicity, indicating their potential for drug development. These findings justify further in vitro assessment of the compounds against YFV and in vivo testing in animal models. This strategy seems to be an efficient approach for discovering antiviral compounds against YFV. Such discoveries hold promise not only in combating YFV but also in addressing a spectrum of other flaviviruses.

Low-lying coastal communities are often threatened by compound flooding (CF), which can be determined through the joint occurrence of storm surges, rainfall and river discharge either successively or in close succession. The trivariate distribution can demonstrate the risk of the compound phenomenon more realistically rather than considering each contributing factor independently or in a pairwise dependency. Recently vine copula has been recognized as the highly flexible approach to constructing a higher dimensional joint density framework. In such construction, parametric class copula with parametric univariate marginal distributions is often involved. Such incorporation can lack flexibility due to parametric functions with prior distribution assumptions about their univariate marginal and/or copula joint density. This study introduces the vine copula approach in a nonparametric setting by introducing Bernstein and Beta kernel copula density in establishing trivariate flood dependence. The proposed model is applied to 46 years of flood characteristics collected on the west coast of Canada. The univariate flood marginal distribution is modelled using nonparametric kernel density estimation (KDE). The 2-D Bernstein estimator and Beta kernel copulas estimator are tested independently in capturing pairwise dependencies to establish D-vine structure in a stage-wise nesting approach in three alternative ways, each by permutating the location of the conditioning variable. The best-fitted vine structure is selected using goodness-of-fit (GOF) test statistics. The performance of the nonparametric vine approach is also compared with the vine constructed in the parametric and semiparametric fitting procedure. Investigation reveals that the D-vine constructed using Bernstein copula with normal KDE marginals nonparametrically performed well in capturing dependence of the compound events. Finally, the derived nonparametric model is used in the estimation of trivariate OR- and AND-joint return periods, further employed in estimating failure probability (FP) statistics. The trivariate return periods for the AND-joint case are higher than for the OR-joint case for the same flood combination. Also, the trivariate flood hazard results in a high-value FP than bivariate and univariate events. Ignoring the trivariate dependence could result in the underestimation of FP

This paper presents a two-dimensional mathematical model of compound eye vision. Such a model is useful for solving navigation issues for autonomous mobile robots on the ground plane. The model is inspired by the insect compound eye that consists of ommatidia, which are tiny independent photoreception units, each of which combines a cornea, lens, and rhabdom. The model describes the planar binocular compound eye vision, focusing on measuring distance and azimuth to a circular feature with an arbitrary size. The model provides a necessary and sufficient condition for the visibility of a circular feature by each ommatidium. On this basis, an algorithm is built for generating a training data set to create two deep neural networks (DNN): the first detects the distance, and the second detects the azimuth to a circular feature. The hyperparameter tuning and the configurations of both networks are described. Experimental results showed that the proposed method could effectively and accurately detect the distance and azimuth to objects.

To understand the mystery of final unification, in our earlier publications, we proposed two bold concepts: 1) There exist three atomic gravitational constants associated with electroweak, strong and electromagnetic interactions. 2) There exists a strong elementary charge in such a way that its squared ratio with normal elementary charge is close to reciprocal of the strong coupling constant. In this paper we propose that, can be considered as a compound physical constant associated with proton mass, electron mass and the three atomic gravitational constants. With these ideas, an attempt is made to understand nuclear stability and binding energy. In this new approach, nuclear binding energy can be fitted with four simple terms having one unique energy coefficient with a formula, where is an estimated mean stable mass number. With this new approach, Newtonian gravitational constant can be estimated in a verifiable approach with a model relation of the form, where is the Fine structure constant. Estimated and is 62 ppm higher than the CODATA recommended It needs further investigation. Proceeding further, an attempt is made to fit the recommended quark masses.

The terpolymers of N-vinylpyrrolidone (VP) with acrylic acid and triethylene glycol methacrylate were synthesized with more than 90% yield by radical copolymerization in ethanol from monomeric mixtures of different composition (98 : 2 : 2, 95 : 5: 2 and 98 : 2: 5). Their physical and chemical characteristics such as monomer composition, absolute molecular masses and hy-drodynamic radii in aqueous media at different temperature were determined. The temperature effect on the behavior of terpolymers in water and aqueous saline buffer solution with pH 7.4 has been studied and the ability of a copolymer enriched with dimethacrylates units was discovered to respond to a temperature change in these media. On the basis of terpolymers and linear polyvi-nylpyrrolidone (PVP), polymer compositions of hydrophobic dye methyl pheophorbide a, MPP, that is fluorescent in the red region of the spectrum, were obtained; the sizes of the polymer nanostructures of MPP in water were determined. The structures based on terpolymers were demonstrated to be more stable than MPP-PVP ones. It was carried out the quantum-chemical modelling of the possible structures of MPP-copolymer that formed as a result of intermolecular interaction between MPP and terpolymer’s chains; the possibility of the formation of hydrogen bonds between the donors of the electrons of terpolymer units and the proton donors of the MPP molecule was shown. Using the MTT test, it was established that copolymers of various compositions are low toxic for non-tumor Vero cells and HeLa tumor cells. It was shown that the cytotoxicity of polymer particles loaded with MPP for FetMSC and HeLa cells increased. Using fluorescence microscopy, the accumulation and distribution of polymer particles in non-tumor (FetMSC) and tumor (HeLa) cells was studied and an increase in the accumulation of MPP with both types of particles was shown.

In photolithography process, nanometer level precise, wavefront aberration models enable the machine to be able to meet the overlay (OVL) drift and critical dimension (CD) specifications. Software control algorithms take as input these models and correct any expected wavefront imperfections before reaching the wafer. In such way a near optimal image is exposed on the wafer surface. Optimizing the parameters of these models though, involves several time costly sensor measurements which reduce the throughput performance, in terms of exposed wafers per hour, of the machine. In that case, photolithography machines come across the trade-off between throughput and quality. Therefore one of the most common Optimal Experimental Design (OED) problems in photolithography machines (and not only) is how to choose the minimum amount of sensor measurements that will provide the maximum amount of information. Additionally, each sensor measurement corresponds to a point on the wafer surface and therefore we must measure uniformly around the wafer surface as well. In order to solve this problem, we propose a Sensor Marks Selection Algorithm which exploits Genetic Algorithms. The proposed solution first selects a pool of points that qualify as candidates to be selected in order to meet the uniformity constraint. Then, the point that provides the maximum amount of information, quantified by the Fisher based criteria of G, D and A-Optimality, is selected and added to the measurement scheme. This process though is considered "greedy", and for this reason Genetic Algorithms (GA) are exploited to further improve the solution. By repeating in parallel the "greedy" part several times we get an initial population that will be the input to our GA. This meta-heuristic approach outperforms the "greedy" approach significantly. The proposed solution is applied in a real life semiconductors industry use case and achieves interesting industry and academical results as well.

Chemotherapy represents the most applied approach to cancer treatment. Owing to the frequent onset of chemoresistance and tumor relapses, there is an urgent need to discover novel and more effective anticancer drugs. In search for therapeutic alternatives to treat the cancer disease, a se-ries of hybrid pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered with hydrazide-hydrazones, 5a-h, was synthesized from condensation reaction of pyrazolopyrimidinone-hydrazide 4 with a series of arylaldehydes in EtOH, in acid catalysis. In vitro assessment of antiproliferative effects against MCF-7 breast cancer cells, unveiled that 5a, 5e, 5g, and 5h were the most effective compounds of the series and exerted their cytotoxic activity through apoptosis induction and G0/G1 phase cell-cycle arrest. To explore their mechanism at a molecular level, 5a, 5e, 5g, and 5h were evalu-ated for their binding interactions with two well-known anticancer targets, namely the epider-mal growth factor receptor (EGFR) and the G-quadruplex DNA structures. Molecular docking simulations highlighted high binding affinity of 5a, 5e, 5g, and 5h towards EGFR. CD experi-ments suggested 5a as a stabilizer agent of the G-quadruplex from the KRAS oncogene promot-er. In the light of these findings, we propose the pyrazolo-pyrimidinone scaffold bearing a hy-drazide-hydrazone moiety as a lead skeleton for designing novel anticancer compounds.

The agonist-antagonist myoneural interface (AMI), a surgical method to reinnervate physiologically-relevant proprioceptive feedback for control of limb prostheses, has demonstrated the ability to provide natural afferent sensations for limb amputees when actuating their prostheses. Following an AMI surgery, one potential challenge is atrophy of the disused muscles, which would weaken the reinnervation efficacy of AMI. It is well known that electrical muscle stimulus (EMS) can reduce the muscle atrophy. In this study, we conducted an animal investigation to explore whether the EMS can significantly improve the electrophysiological performance of AMI. The AMI surgery was performed in 14 rats, in which the distal tendons of bilateral solei donors were connected and positioned on the surface of the left biceps femoris. Subsequently, the left tibial nerve and the common peroneus nerve were sutured onto the ends of the connected donor solei. Two stimulation electrodes were affixed onto the ends of the donor solei for EMS delivery. The AMI rats were randomly divided into two groups. One group regularly received the EMS treatment (designated as EMS_on) for eight weeks and another was no EMS (designated as EMS_off). Two physiological parameters, nerve conduction velocity (NCV) and motor unit number, were derived from the electrically evoked compound action potential (CAP) signals to assess the electrophysiological performance of AMI. Our experimental results demonstrated that the reinnervated muscles of the EMS_on group generated higher CAP signals in comparison to the EMS_off group. Both NCV and motor unit number were significantly elevated in the EMS_on group. Moreover, the EMS_on group displayed statistically higher CAP signals on the indirectly activated proprioceptive afferents than the EMS_off group. These findings may suggested that the EMS treatment would be promise in enhancing the electrophysiological performance and facilitating the reinnervation process of AMI.

Humans are often exposed to various environmental contaminants, among which phthalates are prevalent due to their extensive use as plasticizers in various consumer goods. Di(2-ethylhexyl) phthalate (DEHP), a widely used phthalate, is recognized as an endocrine disruptor chemical (EDC). DEHP is reported to affect various organs. Few studies have addressed the effects of phthalates on bone. However, the effects of DEHP on the bone forming cells (osteoblasts) are obscure. The present study was peformed to determine the cytotoxic effects of DEHP on human osteoblasts in vitro and to delineate the mechansims. In this study, we exposed the human osteo-blastic cell line MG-63 to various concentrations of DEHP (1, 25, 50 and 100 µM) for 24, 48 and 72 h. Cell viability was assessed by MTT assay. Total RNA and protein were collected after 48 h treatment with 1 and 100 µM DEHP and determined for the mRNA and/or protein expression of alkaline phosphatase (ALP), sex steroid receptors (androgen and estrogen receptors), receptor activator of nuclear factor kappa-Β ligand (RANKL), runt-related transcription factor 2 (RUNX2) and peroxisome proliferator-activated receptor alpha (PPARα). The mRNA expression was stud-ied by real-time RT-PCR analysis and the protein expression was determined by western blot analysis. Statistical analyses were done by one-way analysis of variance (ANOVA) followed by the Students–Newman–Keuls (SNK) test. The exposure of MG-63 cells to DEHP caused a signifi-cant decrease in osteoblast viability in all the treatment groups and at all the time points stud-ied. Interestingly, DEHP exposure decreased the mRNA expression of ALP, a bone formation marker. DEHP had differential effects on estrogen receptor alpha (ERα) mRNA and protein ex-pression. However, DEHP treatment downregulated the mRNA and protein expression of ERβ, and androgen receptor (AR). Surprisingly, DEHP downregulated the RANKL mRNA expression. DEHP decreased the protein expression of RUNX2, the key transcription factor and master regu-lator of bone formation. Furthermore, DEHP increased the PPARα protein expression in the os-teoblasts. Importantly, DEHP increased the reactive oxygen species (ROS) molecules and thus oxidative stress in osteoblasts, as observed by increased hydrogen peroxide, hydroxyl radical levels and lipid peroxidation. On the other hand, it decreased the enzymatic and non-enzymatic antioxidant levels namely catalase, superoxide dismutase, glutathione peroxidase activity and reduced glutathione. Our study demonstrated that in vitro exposure to DEHP reduces the osteo-blast viability possibly through alterations in the oxidant-antioxidant system and modulation of the key genes involved in bone formation, highlighting the cytotoxic effects of DEHP on bone forming cells.

A novel cytoplasmic dye decolorizing peroxidase from Dictyostelium discoideum was investigated that oxidizes anthraquinone dyes, lignin model compounds and general peroxidase substrates like ABTS efficiently. Unlike related enzymes, an aspartate residue replaces the first glycine of the conserved GXXDG motif in Dictyostelium DyPA. In solution, Dictyostelium DyPA exists as a stable dimer with the side chain of Asp146 contributing to the stabilization of the dimer interface by extending the hydrogen bond network connecting two monomers. To gain mechanistic insights, we solved the Dictyostelium DyPA structures in the absence of substrate as well as in the presence of potassium cyanide and veratryl alcohol to 1.7, 1.85, and 1.6 Å resolution, respectively. The active site of Dictyostelium DyPA has a hexa-coordinated heme iron with a histidine residue at the proximal axial position and either an activated oxygen or CN^- molecule at the distal axial position. Asp149 is in an optimal conformation to accept a proton from H₂O₂ during the formation of compound I. Two potential distal solvent channels and a conserved shallow pocket leading to the heme molecule were found in Dictyostelium DyPA. Further, we identified two substrate-binding pockets per monomer in Dictyostelium DyPA at the dimer interface. Long-range electron transfer pathways associated with a hydrogen-bonding network that connects the substrate-binding sites with the heme moiety are described.

Platelets have long been associated with sustaining the balance between hemostasis and thrombosis. Platelets, however, are also involved in a wide range of biological activities, including inflammation, immunology, wound healing, cancer biology, and angiogenesis. Platelets' diverse roles are mediated by the expression of various adhesive and immune receptors and the secretion of a diverse array of bioactive proteins, ions stored in granules, and several lipid mediators. Platelets also release pro-inflammatory and anti-inflammatory, and angiogenic factors and shed microparticles into the bloodstream. The challenge for therapeutic intervention in non-hemostatic disease is identifying the factors that primarily inhibit specific targets implicated in platelets' complicated contribution to inflammation or tumor growth while leaving their hemostatic function intact. In addition, blood platelets are involved in infection and innate and adaptive immunity by mediating complicated vascular homeostasis via specialized receptors and granule release, RNA transfer, and mitochondrial secretion. Anti-platelet drugs/bioactive compounds are developed based on their platelet anti-aggregatory properties; however, very little information is available on their effects on non-hemostatic function. Therefore, a better understanding of the impact of the anti-platelet bioactive on the platelets' diverse roles and mechanisms may help develop new strategies and prevent CVD and other diseases. In this review, a comprehensive overview of platelet multifunctional roles in CVD and other diseases and dietary factors' modulatory effects are described.

There are many molecules used as drug carrier. TUD-1 is a newly synthesized mesoporous silica (SM) molecule possess two important features; consists of mesoporous so it is very suitable to be drug carrier in addition to that it has the ability to induce apoptosis in cancer cells. However, the effect of TUD-1 appears to act as cell death inducer, regardless of whether it is necrosis or apoptosis. Unfortunately, recent studies indicate that a proportion of cells undergo necrosis rather than apoptosis, which limits the use of TUD-1 as a secure treatment. On the other hand, lithium considered as necrosis inhibitor element. Hence, current study based on the idea of production a new Li/TUD-1 by incorporated mesoporous silica (TUD-1 type) with lithium in order to produce a new compound that has the ability to activate apoptosis by mesoporous silica (TUD-1 type) and at the same time can inhibit the activity of necrosis by lithium. Herein, lithium was incorporated in TUD-1 mesoporous silica by using sol-gel technique in one step synthesis procedure. Moreover, lithium was incorporated in TUD-1 with different loading in order to form different active sites such as isolated lithium ions, nanoparticles of Li2O, and bulky crystals of Li2O. The ability of the new compounds to induce apoptosis and prevent necrosis was evaluated on three different types of cancer cell lines which are; liver HepG-2, Breast MCF-7 and colon HCT116. The obtained results show that Li/TUD-1has the ability to control necrosis and thus reduce the side effects of treatments containing silica in the case of lithium has been added to them, especially in chronic cases. This has been demonstrated by the significant increase in the IC50 value and cell viability comparing to control groups. Consequently, the idea is new, so it definitely needs more develop and test with materials that have more apoptotic impact than silica in order to induce apoptosis without induction of necrosis.