We introduce a new class of Vertex Operator Algebras Y+ and their duals, which generalize the standard W-algebras WN of type sl(N). These algebras can be defined in terms of junctions of boundary conditions and interfaces in the GL-twisted N = 4 Super Yang Mills gauge theory. The aim of these technical calculations is to find the relation of these ortho-symplectic Y-algebras to truncations of even W\infinity.

A series of novel N-n-butyl-1,8-naphthalimide derivatives were synthesized via a three-step reaction involving nucleophilic substitution and acylation. All of the compounds were characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis, and the crystal structure of N-n-butyl-4-[N’,N’-bis(2`,4`-dichlorobenzoyl)ethylamino]-1,8-naphthalimide was determined. The π-π stacking interactions and hydrogen bonds between the two molecular core planes (naphthalimide ring) and the van der Waals forces between the flexible n-butyl groups resulted in a 3D long-chain structure. The UV-vis and fluorescence properties of the title compounds were investigated. The results indicated that the monosubstituted 1,8-naphthalimide derivatives bearing an electron-donating group on the benzene ring or a structure with a larger conjugative effect exhibited enhanced fluorescence properties.

Marine sponges, a well documented prolific source of natural products, harbors numerous microbial communities believed to possess N-acyl homoserine lactones (AHLs) mediated Quorum sensing (QS) as one of the mechanisms of interaction. Bacteria and eukaryotic organisms are known to produce molecules that can interfere with QS signaling, thus affecting microbial genetic regulation and function. In the present study, we established the potential for production of both QS signal molecules as well as QS interfering molecules (QSI) in the same sponge species Sarcotragus spinosulus. A total of eighteen saturated acyl chain AHLs were identified along with six putative unsaturated acyl chain AHLs. Bioassay guided purification led to the isolation of two brominated metabolites with QS-interfering activity. The structures of these compounds were elucidated by comparative spectral analysis of 1HNMR and HR-MS data and was identified as 3-Br-N-methyltyramine (1) and 5,6-dibromo-N,N-dimethyltryptamine (2). The QSI activity of compounds 1 and 2 were evaluated using reporter gene assays for long- and short-chain signals (E. coli pSB1075 and E. coli pSB401) and was confirmed by measuring dose dependent inhibition of proteolytic activity and pyocyanin production in P. aeruginosa PAO1. The obtained results showed the co-existence of QS and QSI in S. spinosulus, a complex network which may mediate the orchestrated function of the microbiome within the sponge holobiont.

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

Marine lipids are recognized for their health promoting features, mainly for being the primary sources of omega-3 fatty acids, and therefore critical for human nutrition in an age when the global supply for these nutrients is experiencing an unprecedent pressure due to an ever-increasing demand. The seafood industry originates a considerable yield of co-products worldwide that, while already explored for other purposes, remain mostly undervalued as sustainable sources of healthy lipids, often being explored for low value oil production. These co-products are especially appealing as lipid sources since, besides the well-known nutritional upside of marine animal fat, particularly rich in omega-3 polyunsaturated fatty acids (PUFAs), they have also interesting bioactive properties, which may garner them further interest, not only as food, but also for other high-end applications. Besides the added value that these co-products may represent as valuable lipid sources, there is also the obvious ecological upside of reducing seafood industry waste. In this sense, repurposing these bioresources will contribute to a more sustainable use of marine animal food, reducing the strain on already heavily depleted seafood stocks. Therefore, untapping the potential of marine animal co-products as valuable lipid sources aligns with both health and environmental goals by guaranteeing additional sources of healthy lipids and promoting more eco-conscious practices.

Allergies are a common and increasing health problem affecting millions of people worldwide. In addition to genetic predisposition, this increase in allergic cases is attributed to air pollution, climate change, more time spent indoors, lack of physical activity, and alterations in eating habits. The Mediterranean diet (MD), which includes a lot of fruits and vegetables, whole grains, legumes, nuts, olive oil and fish has been linked to a variety of health benefits, including a lower risk of chronic and allergic diseases. The purpose of this paper is to explore the effects of the dietary components of the MD on food allergies. Electronic databases PubMed, Scopus, Science Direct, and EBSCO were used to conduct this systematic review up to March 2023. 696 studies were initially identified and nine were included (five human and four animal studies). The findings of this review showed an overall beneficial effect between the food components of the MD and food allergies. Although the results are promising, the limited number of studies highlights the need for more research.

Polycystic ovary syndrome (PCOS) usually comes along with metabolic disturbances attributed to androgen excess and obesity, but the contribution of each has not been defined, and the occurrence of metabolic disturbances is frequently not investigated. We evaluated 99 PCOS and 41 non-PCOS women. Clinical biomarkers of glucose-, liver-, and endothelial-related metabolic alterations were measured; participants were categorized into four groups according with obesity (OB) and hyperandrogenemia (HA) statuses: Healthy (no-HA, lean), HA (HA, lean), OB (no-HA, OB), and HAOB (HA, OB). Metabolic disturbances were highly frequent in PCOS women (70%). BMI correlated with all biomarkers, while free testosterone (FT) only with glucose- and hepatic-related indicators. Despite insulin sensitivity and liver enzymes were associated with FT, women with obesity exhibited lower M [coeff = 8.56 – 0.080(FT) –3.71(Ob); p <0.001)] and higher aspartate aminotransferase (coeff = 26.27 + 0.532(FT) + 8.08(Ob); p = 0.015)] than lean at the same level of FT. Women with obesity exhibited greater risk of metabolic disorders than lean, independently of hyperandrogenemia. Clinicians are compelled to search for metabolic alterations in PCOS women; obesity must be handled in all cases, but hyperandrogenemia needs to be managed also in those with glucose- or liver-related disturbances.

Japan Aerospace Exploration Agency (JAXA) is going to launch Advanced Land Observing Satellite 3 (ALOS-3) after 2022. ALOS-3 satellite is capable of observing global land areas with wide swath (4000 km along-track direction and 70 km cross-track direction) at high spatial resolution (panchromatic: 0.8m, multispectral: 3.2m). Maintenance and updating of land cover and vegetation information at national level is one of the major goals of the ALOS-3 mission. This paper presents the potential of simulated ALOS-3 images for the classification and mapping of land cover and vegetation types at Genus-Physiognomy-Ecosystem (GPE) level. We acquired and simulated WorldView-3 images according to the configuration of the ALOS-3 satellite sensor and the simulated ALOS-3 images were utilized for the classification and mapping of land cover and vegetation types in three sites (Hakkoda, Zao, and Shiranuka) in northern Japan. This research dealt with 17 land cover and vegetation types in Hakkoda site, 25 land cover and vegetation types in Zao site, and 12 land cover and vegetation types in Shiranuka site. Ground truth data were newly collected in three sites, and we employed eXtreme Gradient Boosting (XGBoost) classifier with the implementation of 10-fold cross-validation method for assessing the potential of ALOS-3S images. The classification accuracies obtained in Hakkoda, Zao, and Shiranuka sites in terms of f1-score were 0.810, 0.729, and 0.805 respectively. The fine scale (3.2m) land cover and vegetation maps produced in the study sites showed clear and detailed view of the distribution of plant communities. Regardless of the limited number of the temporal images, ALOS-3S images showed high potential (at least 0.729 F1-score) for the land cover and vegetation classification in all three sites. The availability of more cloud free temporal scenes is expected for improved classification and mapping in the future.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients. TPEN (N, N, N’, N’-tetrakis(2-pyridylmethyl)-ethylenediamine).is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cells. Consequently, it has been suggested that TPEN could be a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like model, for example, the bloodstream and bone marrow (BM), in vitro. This investigation is an extension of a previous study that dealt with the effect of TPEN on ex vivo isolated/purified refractory B-ALL cells. Here, we evaluated the effect of TPEN on whole BM from nonleukemic patients (control) or pediatric patients diagnosed with de novo B-ALL or refractory B-ALL cells by analyzing the hematopoietic cell lineage marker CD34/CD19. Although TPEN was innocuous to nonleukemic BM (n=3), we found that TPEN significantly induced apoptosis in de novo (n = 5) and refractory B-ALL (n = 6) leukemic cell populations. Moreover, TPEN significantly increased the counts of cells positive for the oxidation of the stress sensor protein DJ-1, a sign of the formation of H2O2, and significantly increased the counts of cells positive for the pro-apoptotic proteins TP53, PUMA, and CASPASE-3 (CASP-3), indicative of apoptosis, in B-ALL cells. We demonstrate that TPEN selectively eliminates B-ALL cells independent of age, diagnosis status (de novo or refractory), sex, karyotype, or immunophenotype. Understanding TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic oxidation-inducing anticancer agents.

An introductory course of Arka Dhyana, also known as Intuitive Meditation (IM), consisting of five sessions, was offered to an international audience via Zoom technology. Participants were shown how to connect to their deeper self, essence or soul by bringing their I-ego-awareness from the thinking mind, often associated with the frontal part of the brain, to 19 energetic stations in the body including the heart centre. In this limited study, evaluation was both process and outcome orientated and included HeartMath (HM) Inner Balance or emWave2 electronic technology to measure mean coherence and achievement before and after each session. A highly significant increase in both coherence and achievement in six participants was found, which was also reflected in a reported increase in wellbeing related to feelings in qualitative statements indicating changes in levels of consciousness and individual transformative experiences as predicted by the Theory of the Six Main Levels of Consciousness.

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

In this paper, we present an extended version of the Hadi-Vencheh model for multiple criteria ABC inventory classification. The proposed model is a nonlinear weighted product model (WPM) which determines a common set of weights for all the items. Our proposed nonlinear WPM incorporates multiple criteria with different measure units, without converting the performance of each inventory item in terms of each criterion into a normalized attribute value, thereby providing an improvement over the model proposed by Hadi-Vencheh. Our study mainly includes various criteria for ABC classification, and demonstrates an efficient algorithm for solving nonlinear programming problems in which the feasible solution set does not have to be convex. The algorithm presented in this study improves the solution efficiency of the Canonical Coordinates Method (CCM) algorithm substantially when applied to large scale, nonlinear programming problems. The modified algorithm was tested to compare our proposed model results to the results derived using the Hadi-Vencheh model and demonstrate the algorithm's efficacy. The practical implications of the study are to develop an efficient nonlinear optimization solver by optimizing the quality of existing solutions, thus improving time and space efficiency.

Easy to use satellite-based water quality visualizations are needed for monitoring and understanding coastal and inland waters, but to date, no publicly accessible real-time global visualization system was in place. Here we introduce the Ulyssys Water Quality Viewer (UWQV), a Sentinel Hub EO Browser Custom script designed for qualitative views of aquatic chlorophyll and suspended sediment concentrations. The viewer avoids unmixing of the chlorophyll and suspended sediment spectral signal by visualizing these parameters together, with high concentrations of suspended sediment obscuring chlorophyll if present. Cloud masking uses the Hollstein and Braaten algorithms (existing EO Browser custom script code), additionally water surfaces are masked using the Normalized Differential Water Index. Chlorophyll is estimated using reflectance line height-based indicators such as fluorescence line height and maximum chlorophyll index. Suspended sediment is visualized based on single-band reflectances at 620 or 700 nm. Data sources are Sentinel-2 and Sentinel-3 images, allowing either 20 m spatial resolution or up to daily imaging. This visualization system is easy to operate and interpret, and combined with the data service capacity of the Sentinel Hub, it is expected that UWQV will contribute to monitoring of remote water bodies and to our overall understanding of physical limnology and aquatic ecology.

Splines and quasi-interpolation operators are important both in approximation theory and applications. In this paper, we construct a family of quasi-interpolation operators for the bivariate quintic spline spaces S₅³ (∆_mn⁽²⁾). Moreover, the properties of the proposed quasi-interpolation operators are studied, as well as its applications for solving two-dimensional Burgers’ equation and image reconstruction. Some numerical examples show that these methods, which are easy to implement, provide accurate results.

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is reasonable epidemiological cohort data to recommend surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommend that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) should consider HCC surveillance. NITs include fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US or if US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II), can help to identify high risk of incident HCC in NAFLD patients. Innovative parameters including Mac-2 binding protein glycated isomer , type IV collagen 7S, free apoptosis inhibitor of macrophage, combination of single nucleoside polymorphisms are expected to be established. Considering a large number of NAFLD population, optimal screening tests must meet several criteria including high sensitivity, cost effectiveness and availability.

Various attempts to amplify an AQP11 cDNA from tissues of the spiny dogfish (Squalus acanthias) were made. Two pairs of deoxy-inosine-containing degenerate primers were designed based on conserved amino acid sequences from an AQP11 alignment. These primers yielded some faint bands from gill cDNA that were sequenced. Blast searches with the sequences showed they were not AQP11. An elasmobranch AQP11 nucleotide sequence alignment was produced to identify conserved regions to make further degenerate primers. One primer pair produced a short 148bp fragment showing particularly strong expression in gill and intestine. It was sequenced and represented a piece of the AQP11 gene. However, as the fragment may have resulted from contaminating genomic DNA (in total RNA used to make cDNA), 5’ and 3’ RACE was performed to amplify the two ends of the putative cDNA. 5’ and 3’ RACE amplifications depend on the presence of a 5’ cap nucleotide and a poly A tail respectively on the putative AQP11 mRNA. Hence successful amplification was only possible from cDNA and not genomic DNA. Nested RACE amplifications were performed using gill and intestinal RACE cDNA but none of the DNA fragments were AQP11. Consequently, the spiny dogfish AQP11 gene may represent a pseudogene.

Consistent calibration and monitoring is a basic prerequisite for providing reliable time series of global and regional sea level variations from altimetry. The precision of sea level measurements and regional biases for six altimeter missions (Jason-1/2/3, Envisat, Saral, Sentinel-3A) is assessed at eleven GNSS-controlled tide gauge stations in the German Bight (SE North Sea) for the period 2002 to 2019. The gauges are partly located at the open water, partly at the coast close to mudflats. The altimetry is extracted at virtual stations with distances from 2 to 24 km from the gauges. The processing is optimized for the region and adjusted for the comparison with instantaneous tide gauges readings. An empirical correction is developed to account for mean height gradients and slight differences of the tidal dynamics between gauge and altimetry which improves the agreement between the two data sets by 15-75%. The precision of the altimeters is depending on location and mission and is shown to be at least 1.8 to 3.7 cm based on an assumed precision of 2 cm for the gauges. The accuracy of the regional mission biases is strongly dependent on the mean sea surface heights near the stations. The most consistent biases are obtained based on the CLS2011 model with mission dependent accuracies from 1.3 to 3.4 cm. Hence, the GNSS-controlled tide gauges operated operationally by WSV might complement the calibration and monitoring activities at dedicated CalVal stations.

A Staudinger reaction on solid phase between an electronodeficit organic azide such as sulfonyl azide, and the phosphite triester formed upon phosphoramidite coupling is a convenient method for chemical modification of oligonucleotides at the internucleotidic phosphate position. In this work, 4-carboxybenzenesulfonyl azide either with a free carboxy group or in the form of an activated ester such as pentafluorophenyl, 4-nitrophenyl, or pentafluorobenzyl ester were used to introduce a carboxylic acid function to the terminal or internal internucleotidic phosphate of an oligonucleotide via Staudinger reaction. A subsequent treatment with excess primary alkyl amine followed by usual work-up, after prior activation with a suitable peptide coupling agent such as HBTU/HOBt in the case of a free carboxyl, afforded amide-linked oligonucleotide conjugates in good yields including multiple conjugations of up to the exhaustive modification at each phosphate position for a weakly activated pentafluorobenzyl ester, whereas more strongly activated and, thus, more reactive aryl esters provided only single conjugations at the 5′-end. The conjugates synthesized include those with di- and polyamines that introduce a positively charged side-chain to potentially assist intracellular delivery of the oligonucleotide.

Banana is one of the most important fruits in the world due to its status as a major food source for more than 400 million people. Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) causes substantial losses of banana crops every year, and molecular host resistance mechanisms are currently unknown. We here performed a genome-wide analysis of the autophagy related protein 8 (ATG8) family in a wild banana species. The banana genome was found to contain 10 MaATG8 genes. Four MaATG8s formed a gene cluster in the distal part of chromosome 4. Phylogenetic analysis of ATG8 families in banana, Arabidopsis thaliana, Citrus, rice, and ginger revealed five major phylogenetic clades shared by all of these plant species, demonstrating evolutionary conservation of the MaATG8 families. The transcriptomic analysis of plants infected with Foc TR4 showed that almost all of the MaATG8 genes were more highly induced in resistant cultivars than in susceptible cultivars. Finally, MaATG8F was found to interact with MaATG4B in vitro (with yeast two-hybrid assays), and MaATG8F and MaATG4B all positively regulated banana resistance to Foc TR4. Our study provides novel insights into the structure, distribution, evolution, and expression of the MaATG8 family in bananas. Furthermore, the discovery of interactions between MaATG8F and MaATG4 could facilitate future researches of disease resistance genes for genetic improvement of bananas.

Background: Extremely rare progressive diseases like Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) can be neonatally lethal and therefore go undiagnosed or are difficult to treat. Recent sequencing efforts have linked this disease to mutations in GPX4, with consequences in the resulting enzyme, glutathione peroxidase 4. This offers potential diagnostic and therapeutic avenues for those suffering from this disease, though the steps toward these treatments is often convoluted, expensive, and time-consuming. Main body: The CureGPX4 organization was developed to promote awareness of GPX4-related diseases like SSMD, as well as support research that could lead to essential therapeutics for patients. We provide an overview of the 21 published SSMD cases and have compiled additional sequencing data for four previously unpublished individuals to illustrate the genetic component of SSMD, and the role of sequencing data in diagnosis. We outline in detail the steps CureGPX4 has taken to reach milestones of team creation, disease understanding, drug repurposing, and design of future studies. Conclusion: The primary aim of this review is to provide a roadmap for therapy development for rare, ultra-rare, and difficult to diagnose diseases, as well as increase awareness of the genetic component of SSMD. This work will offer a better understanding of GPx4-related diseases, and help guide researchers, clinicians, and patients interested in other rare diseases find a path towards treatments.

Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). We performed a comprehensive search of the literature updated to April 2018, including the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We extracted data on study characteristics and risk of bias in duplicate. Of 423 unique citations, 21 RCTs were included, inherently to 12,635 patients. Both males and females showed reduced risk of death associated with ICIs use (HR 0.73, p<0.001 and HR 0.77, p<0.001, respectively). Subgroup analyses by specific ICI showed similar OS in both genders for anti-PD-1/PDL-1. Anti-CTLA-4 use was associated with longer OS in men only (HR 0.77, p<0.012), with the exception of melanoma (in women, HR 0.80, p=0.006). PFS was longer in men than in women (HR 0.67, p<0.001 and HR 0.77, p=0.100, respectively). Conclusively, ICIs use was associated with more favorable outcomes in men, particularly for anti-CTLA-4 agents. In melanoma, not gender-related factors may influence the anti-tumor immune response evoked by ICIs.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged >=65 years in developed countries. Globally, it affects 30-50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many observational studies, such as AREDS-1 and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high fat and high glucose or fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

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

Recently, due to the decrease in labor force, increase in labor costs, and the desire for improved quality of life, research on robots has been actively conducted to address these issues. However, it is currently difficult to find robots that physically interact with humans. The reason is that the actuators of robots do not have high torque density on their own. To solve this problem, high torque density motors, such as proprioceptive actuators, are being researched. However, the torque density is still insufficient for physical interaction with humans, so we have developed a motor with higher torque density. However, high torque density motors have the disadvantage of lower speed characteristics due to increased Back-EMF. Therefore, to address the deterioration of speed characteristics in the developed motor, we applied the Independent 3-Phase winding structure to improve the speed characteristics. Consequently, through comparison with Y-Connection and Delta-Connection, we propose the most suitable winding structure for high torque density motors intended for physical interaction with humans.

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

Recently, the Third Generation Partnership Project (3GPP) introduced the New Radio (NR) technology for Vehicle-to-everything (V2X) communication to enable delay-sensitive and bandwidth-hungry applications in vehicular communication. The NR system is strategically crafted to complement the existing Long Term Evolution (LTE) Cellular-Vehicle-to-Everything (C-V2X) infrastructure, particularly to support advanced services such as the operation of automated vehicles. It is widely anticipated that the 5th generation (5G) NR system will surpass LTE C-V2X in terms of achieving superior performance in scenarios characterized by high throughput, low latency, and enhanced reliability, especially in the context of congested traffic conditions and a diverse range of vehicular applications. This article will provide a comprehensive literature review on vehicular communications from Dedicated Short Range Communication (DSRC) to NR V2X. Subsequently, it delves into a detailed examination of the challenges and opportunities inherent in NR V2X technology. Finally, we proceed to elucidate the process of creating and analyzing an open-source 5G NR V2X module in network simulation-3 (ns-3) and then demonstrate the NR V2X performance in terms of different key performance indicators implemented through diverse operational scenarios.

: The article examines the regularities of structure formation of ultrafine fibers based on poly-3-hydroxybutyrat under the influence of technological (electrical conductivity, viscosity), molecular (molecular weight), and external factors (low-molecular and nanodispersed substances of different chemical nature). Systems with polar substances are characterized by the presence of intermolecular interactions and the formation of a more perfect crystalline fiber structure. Changes in technological and molecular characteristics affect the fiber formation process, resulting in alterations in the morphology of the non-woven fabric, fiber geometry, and supramolecular fiber structure. Polymer molecular weight, electrical conductivity, and solution viscosity influence fiber formation and fiber diameter. The fiber structure is heterogeneous, consisting of both crystalline and non-equilibrium amorphous phases. This is significant in the development of matrix-fibrillar systems for drug delivery, bioactive substances, antiseptics, tissue engineering constructs, tissue engineering scaffolds, artificial biodegradable implants, sorbents, and other applications.

2-(5,6-diphenyl-1,2,4-triazin-3-yl)pyridinium dichloroiodate (I) (1) was synthesized by reacting 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine with ICl in dichloromethane solution. The structural characterization of 1 by SC-XRD analysis was accompanied by elemental analysis, FT-IR, and FT-Raman spectroscopy measurements.

Synthesis of a novel series of chromen-3-yl-pyridine moieties. IR, NMR, and MS spectroscopy were used to confirm the structure of these novel compounds and study of antitumor activity of these compounds. The structure activity relationship investigation demonstrated that 2,4-diamino-5-(3-methoxyphenyl)-7-(2-oxo-2H-chromen-3-yl)-1,8-naphthyridine-3-carbonitrile (16), was more effective and naphthyridine-3-carbonitrile derivatives 17, 18 and pyrido[2,3-d]pyrimidine derivative 12, while compounds 5a,b, 9c, 11, 13 and 14 were moderate activity for antitumor activities.

In green chemistry, filamentous fungi are regarded as a kind of robust microorganism for the biotransformation of natural products. Nonetheless, the screening of microorganisms is crucial for the effective biotransformation of natural products such as phenazine compounds. The precursor metabolite of most phenazine derivatives in Pseudomonas spp. is phenazine-1-carboxylic acid (PCA), the key constituent of shenqinmycin, widely used to control rice sheath blight in southern China. In this study, a new fungus strain Aspergillus sclerotiorum was isolated, which can efficiently convert PCA into 3-hydroxy-phenazine 1-carboxylic acid (3-OH-PCA). Moreover, an effective whole cells biotransformation system was constructed by screening optimal reaction conditions and carbon sources. Hence, Aspergillus sclerotiorum exhibited desirable adaptation by consumption of different carbon sources and maximum whole cell biomass (10.6 g/L DCW) was obtained as a biocatalyst from glucose. Optimal conditions for whole-cell biocatalysis of PCA were evaluated, including PCA concentration of 1120 mg/L, pH 7.0, temperature of 25°C, rotation rate 200 rpm and dry cell weight 15 g/L for 60 h, thus 1060 mg/L of 3-OH-PCA was obtained and the conversion efficiency of PCA was 94%. Hence, the results of repeated batch mood revealed that the biotransformation efficiency of fungus pellets reduced with each subsequent cycle but remained stable in all five cycles with the provision of glucose supplement. These findings open the prospective of using filamentous fungi for the whole cell biocatalysis of phenazine in enormous amount and efficient production of 3-OH-PCA. Moreover, these results laid the foundation for further research to disclose the genetic based mechanism of the strain responsible for PCA biotransformation.

Cesium lead iodide (CsPbI3) perovskite nanocrystals (NCs) are a promising material for red light-emitting diodes (LEDs) due to their excellent color-purity and high luminous efficiency. However, small-sized CsPbI3 colloidal NCs, such as nanocubes, used in LEDs suffer from confinement effects, negatively impacting their photoluminescence quantum yield (PLQY) and overall efficiency. Here, we introduced YCl3 into the CsPbI3 perovskite, which formed anisotropic, one-dimensional (1D) nanorods. This was achieved by taking advantage of the difference in bond energies between Cl− and I− ions, which caused YCl3 to promote the anisotropic growth of CsPbI3 NCs. The YCl3-based nanorods improved the PLQY and storage stability by passivating the defects reducing the nonradiative recombination rates. When the YCl3-substituted CsPbI3 nanorods are applied to the emissive layer in LEDs, we achieve an external quantum efficiency of ~3.16% which is 1.86-fold higher than the pristine CsPbI3 NCs (1.69%) based LED. Notably, the ratio of horizontal transition dipole moments (TDMs) in the anisotropic YCl3:CsPbI3 nanorods was determined to be 75%, which is higher than the isotropically oriented TDMs in CsPbI3 nanocrystals (67%). This increased TDM ratio led to higher light outcoupling efficiency in nanorods-based LEDs. Overall, the results suggest that YCl3-substituted CsPbI3 nanorods could be promising for achieving high-performance perovskite LEDs.

In this paper, four types of open service signals of BDS-3 satellite (B1I, B1C, B2a, and B3I) and B2I signals broadcasted by BDS-2 satellites were used in the time frequency transfer and positioning experiments with signal coexisting in BDS system, and the single frequency PPP (precise point positioning) method was used. Modified GRoup And PHase Ionospheric Correction (GRAPHIC) method was proposed and verified by the experiment. The results show that 18 selected stations can achieve decimeter-level positioning results with single frequency. Compared with the general observation method, the proposed modified GRAPHIC method improves the stability and precision of positioning and timing significantly, and the positioning accuracy of 5 frequency signals is increased 40.4%, 32.2%, 80.3%, 12.4%, and 10.3%, respectively. The frequency stability can reach the same accuracy as that of dual-frequency with BDS in the current state.

Inflammation mediators enhance the activity of connexin (Cx) hemichannels especially in the epithelial and endothelial tissues. As potential release route for injury signals like (oligo)nucleotides, Cx hemichannels may contribute to long lasting inflammation. Specific inhibition of Cx hemichannels may therefore be a mode of prevention and treatment of long lasting, chronic sterile inflammation. The activity of Cx hemichannels was analysed in N2A and HeLa cells transfected with human Cx26 and Cx46 as well as in Calu-3 cells using the dye uptake as functional assay. Moreover, possible impact of the bioactive phenolic agents CVB2-61 and CVB4-57 on the barrier function of epithelial cells was analysed using Calu-3 cells. Both agents inhibited the dye uptake in N2A cells expressing Cx26 (> 5 µM) and Cx46 (> 20 µM). In Calu-3 cells, CVB2-61 and CVB4-57 reversible inhibited the dye uptake at concentrations as low as 5 µM, without affecting the gap junction communication and barrier function, even at concentrations of 20 µM. While CVB2-61 or CVB4-57 maintained a reduced dye uptake in Calu-3 cells, an enhancement of the dye uptake in response to stimulation of adenosine signaling was still observed after removal of the agents. The report shows that CVB2-61 and CVB4-57 reversible block Cx hemichannels. Deciphering the interaction mechanisms with Cx hemichannels could allow further development of phenolic compounds to target Cx hemichannels for a better and safer use in treatment of pathologies that involve Cx hemichannels.

We present a simplified atmospheric correction algorithm for the snow/ice albedo retrieval using single view satellite measurements. The validation of the technique is performed using Ocean and Land Colour Instrument (OLCI) on board Copernicus Sentinel - 3 satellite and ground spectral or broadband albedo measurements from locations on the Greenland ice sheet and in the French Alps. Through comparison with independent ground observations, the technique is shown to perform accurately in a range of conditions from a 2100 m elevation mid-latitude location in the French Alps to a network of 15 locations across a 2390 m elevation range in seven regions across the Greenland ice sheet. Retrieved broadband albedo is accurate within 5% over a wide (0.5) broadband albedo range of the (N = 4,155) Greenland observations and with no apparent bias.

The Sentinel Application Platform (SNAP) architecture facilitates Earth Observation data processing (http://step.esa.int/main/toolboxes/snap/). In this work we present results from a new Snow Processor for SNAP. We also describe physical principles behind the developed snow property retrieval technique based on the analysis of Ocean and Land Colour Instrument (OLCI) onboard Sentinel-3A/B measurements over clean and polluted snow fields. Using OLCI spectral reflectance measurements in the range 400-1020nm, we derive important snow properties such as spectral and broadband albedo, snow specific surface area, snow extent and grain size on the spatial grid of 300m. The algorithm also incorporates cloud screening and atmospheric correction procedures over snow surfaces. We present validation results using ground measurements from Antarctica, the Greenland ice sheet and the French Alps. We find the spectral albedo retrieved with accuracy of better than 3% on average, making our retrievals sufficient for a variety of applications. Broadband albedo is retrieved with the average accuracy of about 5% over snow. Therefore, the uncertainties of satellite retrievals are close to experimental errors of ground measurements. The retrieved surface grain size shows good agreement with ground observations. Snow specific surface area observations are also consistent with our OLCI retrievals. We present snow albedo and grain size mapping over the inland ice sheet of Greenland for areas including dry snow, melted/melting snow and impurity rich bare ice. The algorithm can be applied to OLCI Sentinel-3 measurements providing an opportunity for creation of long – term snow property records essential for climate monitoring and data assimilation studies - especially in the Arctic region, where we face rapid environmental changes including reduction of snow/ice extent and, therefore, planetary albedo.

The main goal of the Soil Moisture and Ocean Salinity (SMOS) mission over land surfaces is the production of global maps of soil moisture (SM) and vegetation optical depth (τ) based on multi-angular brightness temperature (TB) measurements at L-band. The operational SMOS Level 2 and Level 3 soil moisture algorithms account for different surface effects, such as vegetation opacity and soil roughness at 4 km resolution, in order to produce global retrievals of SM and τ. In this study, we present an alternative SMOS product which was developed by INRA (Institut National de la Recherche Agronomique) and CESBIO (Centre d’Etudes Spatiales de la BIOsphère). This SMOS-INRA-CESBIO (SMOS-IC) product provides daily SM and τ at the global scale and differs from the operational SMOS Level 3 (SMOSL3) product in the treatment of retrievals over heterogeneous pixels. Specifically, SMOS-IC is much simpler and does not account for corrections associated to the antenna pattern and the complex SMOS viewing angle geometry. It considers pixels as homogeneous to avoid uncertainties and errors linked to inconsistent auxiliary data sets which are used to characterize the pixel heterogeneity in the SMOS L3 algorithm. SMOS-IC also differs from the current SMOSL3 product (Version 300, V300) in the values of the effective vegetation scattering albedo (ω) and soil roughness parameters. An inter-comparison is presented in this study based on the use of ECMWF (European Center for Medium range Weather Forecasting) SM outputs and NDVI (Normalized Difference Vegetation Index) from MODIS (Moderate-Resolution Imaging Spectroradiometer). A 6 year (2010-2015) inter-comparison of the SMOS products SMOS-IC and SMOSL3 SM (V300) with ECMWF SM yielded higher correlations and lower ubRMSD (unbiased root mean square difference) for SMOS-IC over most of the pixels. In terms of τ, SMOS-IC τ was found to be better correlated to MODIS NDVI in most regions of the globe, with the exception of the Amazonian basin and of the northern mid-latitudes.

Human milk fat is a concentrated source of energy and provides essential and long chain polyunsaturated fatty acids. According to previous experiments, human milk fat is partially lost during continuous enteral nutrition. However, these experiments were done over relatively short infusion times, and a complete profile of the lost fatty acids was never measured. Whether this lost happens considering longer infusion times or if some fatty acids are lost more than others remain unknown. Pooled breast milk was infused through a feeding tube by a peristaltic pump over a period of 30 minutes and 4, 12 and 24 hours at 2 ml/hour. Adsorbed fat was extracted from the tubes, and the fatty acid composition was analyzed by Gas chromatography-mass spectrometry. Total fat loss (average fatty acid loss) after 24 hours was 0.6 ± 0.1%. Short-medium chain (0.7%, p=0.15), long chain (0.6%, p=0.56) saturated (0.7%, p=0.4), monounsaturated (0.5%, p=0.15), polyunsaturated fatty (0.7%, p=0.15), linoleic (0.7%, p=0.25), and docosahexaenoic acids (0.6%, p=0.56) were not selectively adsorbed to the tube. However, very long chain fatty (0.9%, p=0.04), alpha-linolenic (1.6%, p=0.02) and arachidonic acids (1%, p=0.02) were selectively adsorbed and therefore lost in a greater proportion than other fatty acids. In all cases, the magnitude of the loss was clinically low.

The indole-3-pyruvic acid pathway is the major route for auxin biosynthesis in higher plants. Tryptophan aminotransferases (TAA1/TAR) and members of the YUCCA family of flavin-containing monooxygenases catalyze the conversion of L-tryptophan via indole-3-pyruvic acid into indole-3-acetic acid (IAA). It has been described that locally produced jasmonic acid (JA) in response to mechanical wounding, triggers de novo-formation of IAA through the induction of two YUCCA genes, YUC8 and YUC9. Here, we report the direct involvement of a small number of basic helix-loop-helix transcription factors of the MYC family in this process. We show that the JA-mediated regulation of YUC8 and YUC9 gene expression depends on the abundance of MYC2, MYC3, and MYC4. In support of this observation, seedlings of myc knockout mutants displayed a strongly reduced response to JA-mediated IAA formation. In addition, transactivation assays provided experimental evidence for the binding of the MYC transcription factors to a particular tandem G-box motif abundant in the promoter regions of YUC8 and YUC9, but not in those of the other YUCCA genes. Moreover, we clearly demonstrate that YUC8ox and YUC9ox overexpressing plants show less damage after spider mite infestation, thereby underlining a role of auxin in plant responses toward biotic stress cues.

During the past few years unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking ad-vantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss emerging clinical relevance of advanced diagnostics for cardiovascular diseases - includ-ing those associated with COVID-19 - with a focus on the role of inflammation in cardiomyopa-thies and arrhythmias. Second, we consider newly identified immunological interactions at or-gan and systems level which affect cardiovascular pathogenesis. Thus, studies into immune in-fluences arising from the intestinal system are moving towards therapeutic exploitation. Fur-ther, powerful new research tools have enabled novel insight into brain – immune system inter-actions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress - acting through defined brain regions - upon viral and cardiovas-cular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

This paper presents the PEnsemble 4 model, a sophisticated machine learning framework that integrates IoT-based environmental data to accurately forecast maize yield. With the projected significant growth in global maize demand over the next decade, the inherent risks posed by the crop’s dependence on weather conditions necessitate improved prediction capabilities. The PEnsemble 4 model, developed with high accuracy, incorporates comprehensive datasets encompassing soil attributes, nutrient composition, weather conditions, and UAV-captured vegetation imagery. By employing a combination of Huber and M estimates, the PEnsemble 4 model effectively analyzes temporal patterns in vegetation indices, specifically CIre and NDRE, which serve as reliable indicators of canopy density and plant height. In addition, this research significantly contributes to precision agriculture by offering an efficient and sustainable alternative to conventional farming practices through precise yield predictions. Notably, the PEnsemble 4 model enables earlier estimation, advancing the timeline for yield prediction from the conventional day 100 in the R6 stage to day 79 in the R2 stage. This improvement enhances decision-making processes in farming operations. The remarkable accuracy rate of 91% underscores the importance of adopting a multifaceted data approach that harnesses IoT-derived environmental insights. Additionally, the PEnsemble 4 model extends its benefits beyond yield prediction, facilitating the detection of water and crop stress, as well as disease monitoring in broader agricultural contexts. Ultimately, the PEnsemble 4 model establishes a new standard in maize yield prediction, revolutionizing crop management and protection through the synergistic utilization of IoT and machine learning technologies.

Immune checkpoint inhibition therapy (ICIT) is an emerging field in oncology especially opening new horizons to chemotherapy refractory patients. This paper provides deep insight into immune related adverse events (irAEs) posing a major challenge and drawback to ICIT, and presents right management strategies for very complex complications. Moreover, for the first time in literature, a non-linear mathematical model is introduced to measure the ICIT success rate and to decide about the optimum ICIT duration. Furthermore, a strategy is presented to overcome or to delay the progression after initial good response in a subset of patients.

Large population passages of the SARS-CoV-2 in the past two and a half years have allowed the circulating virus to accumulate an increasing number of mutations in its genome. The most recently emerging Omicron subvariants have the highest number of mutations in the Spike (S) protein gene and these mutations mainly occur in the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the S gene. The eCDC and the WHO recommend partial Sanger sequencing of the SARS-CoV-2 S gene RBD and NTD on the PCR-positive samples in diagnostic laboratories as a practical means of determining the variants of concern to monitor a possible increased transmissibility, increased virulence, or reduced effectiveness of vaccines against them. The author’s diagnostic laboratory has implemented the eCDC/WHO recommendation by sequencing a 398-base segment of the N gene for the definitive detection of SARS-CoV-2 in clinical samples, and sequencing a 445-base segment of the RBD and a 490-509-base segment of the NTD for variant determination. This paper presents 5 selective cases to illustrate the challenges of using Sanger sequencing to diagnose Omicron subvariant when the samples harbor a high level of co-existing minor subvariant sequences with multi-allelic single nucleotide polymorphisms (SNPs) or possible recombinant Omicron subvariants containing a BA.1 NTD and a BA.2 RBD, which can only be detected by using specially designed PCR primers. The current large-scale surveillance programs using next-generation sequencing (NGS) do not face similar problems because NGS focuses on deriving consensus sequence.

Most oral squamous cell carcinomas (OSCCs) arise from oral epithelial dysplasia; however, there is no useful marker for early OSCC detection, likely owing to the inability to continuously observe the carcinoma sequence. We aimed to establish an experimental model to observe changes in the sequential expression pattern of mRNA and protein in the same rat using liquid-based cytology techniques. Cytology specimens were collected from a 4-nitroquinoline 1-oxide-induced rat tongue cancer model at 2, 5, 8, 11, 14, 17, and 21 weeks. We examined candidate biomarker expression using immunocytochemistry and quantitative real-time PCR. The percentage of positively stained nuclei was calculated as the labeling index (LI). All rats had OSCC of the tongue at 21 weeks. Brd4 (Brd4), Myc (c-Myc), and Tp53 (p53) mRNA levels were upregulated during progression from negative for intraepithelial lesion or malignancy to SCC. Brd4- and c-Myc-LI were increased in low- and high-grade squamous intraepithelial lesions and SCC specimens. p53-LI was significantly increased in SCC specimens. Our experimental model allowed the observation of sequential morphological changes and mRNA and protein expression patterns in the same rat during carcinogenesis. By reducing the false negative rate, BRD4 and c-Myc can be useful markers for the early detection of OSCC.

Background: Newer personalized medicine including targeted therapies such as PARP inhibitors and CDK 4/6 inhibitors have shown to improve survival of breast and gynaecological cancer patients. However, efficacy outcomes may be hampered by treatment discontinuation due to targeted therapy-related adverse drug reactions or resistance. Studies suggest that add-on mistletoe (Viscum album L., VA) improves quality of life and ameliorates cytotoxic side effects of standard oncological therapy in cancer patients. The primary objective of this real-world data study was to determine the safety profile of targeted therapy in combination with add-on Helixor® VA therapy in breast and gynecological cancer patients. Methods: The present study is a real-world data study utilizing demographic and treatment data from the accredited national Network Oncology (NO) registry. The study has received ethics approval. The safety profile of targeted with or without Helixor® VA therapy as well as safety - associated variables were evaluated by univariate and adjusted multivariable regression analyses. Results: All stage breast or gynecological cancer patients (n = 242) were on average 54.5±14.2 years old. One hundred and sixty patients (66.1%) were in the control (CTRL, targeted therapy) and 82 patients (33.9%) in the combinational (COMB, targeted plus Helixor® VA therapy) group. The addition of Helixor® VA did not hamper the safety profile (χ2 = 0.107, p-value = 0.99) of targeted therapy. Furthermore, no adverse events and a trend towards an improved targeted therapy adherence were observed in the COMB group. Conclusions: The present study is the first of its kind showing the applicability of Helixor® VA in combination with targeted therapies. The results indicate that add-on Helixor® VA does not negatively alter the safety profile of targeted therapies in breast and gynaecological cancer patients.

Amphetamine is a psychostimulant drug with a high risk of toxicity and death when misused. Abuse of amphetamines is associated with an altered organic profile, which includes omega fatty acids. Low omega fatty acid levels are linked to mental disorders. Using the Comparative Toxicogenomic Database (CTD), we investigated the chemical profile of the brain in amphetamine-related fatalities and the possibility of neurotoxicity. We classified amphetamine cases as low (0-0.5 g/ml), medium (&gt;0.5 to 1.5 g/ml), and high (&gt;1.5 g/ml) based on amphetamine levels in brain samples. All three groups shared 1-octadecene, 1-tridecene, 2,4-di-tert-butylphenol, arachidonic acid, docosahexaenoic acid (DHA), eicosane, and oleylamide. We identified chemical-disease associations using the CTD tools and predict an association between docosahexaenoic and arachidonic acids and curated conditions like autistic disorder, disorders related to cocaine, Alzheimer's disease, and cognitive dysfunction. An amphetamine challenge may cause neurotoxicity in the human brain due to a decrease in omega-3 fatty acids and an increase in oxidative products. Therefore, in cases of amphetamine toxicity, supplement therapy may necessitate preventing omega-3 fatty acid deficiency.

To remain relevant in the green transition, companies are beginning to voluntarily account for the exchange of emissions in their supply chain transactions and using the resulting greenhouse gas inventories for climate resilient decision support. Market advantages of sustainability and transparency see a shift from internal decision support tools to external communication tools which potentially expose companies to the risk of uncovering greenwashing if claims are not supported by transparent data, sound modelling, and a climate just emissions inventory, which considers external impacts connected to the production system. The different methods and standards in place for such greenhouse gas inventories, despite all referring to the ISO life cycle analysis standards and guidelines, present mixed signals and leave room for different interpretations, that may ultimately lead to cascading greenwashing, misleading results, and false successes. The new GHG Protocol Land Sector and Removals Guidance draft addresses this in part. With the GHG Protocol moving into revision periods, we identify gaps that present barriers to companies, or allow for interpretations that goes against the intentions of reporting GHG emissions related to an activity or organisation. The literature agrees that not rectifying these subtle-ties present counterproductive decision support for the green transition’s overall goal: to reduce global emissions.

Either stereo reactants or stereo catalysis from achiral or chiral molecules are prerequisite to obtain pure enantiomeric lipid derivatives. We reviewed a few plausible organic syntheses of phospholipids under prebiotic conditions with a special attention to the starting materials as pro-chiral dihydroxyacetone and dihydroxyacetone phosphate (DHAP), which are the key molecules to break symmetry in phospholipids. The advantages of homochiral membranes compared to those of heterochiral membranes were analysed in term of specific recognition, optimal functions of enzymes, membrane fluidity and topological packing. All biological membranes contain enantiomeric lipids in modern bacteria, eukarya and archaea. The contemporary archaea, comprising of methanogens, halobacteria and thermoacidophiles are living under extreme conditions reminiscent of primitive environment and may indicate the origin of one ancient evolution path of lipid biosynthesis. The analysis of lipid metabolism reveals that all modern cells including archaea synthetize enantiomeric lipid precursors from prochiral DHAP. sn-glycerol-1-phosphate dehydrogenase (G1PDH), usually found in archaea, catalyses the formation of sn-glycerol-1-phosphate (G1P), while sn-glycerol-3-phosphate dehydrogenase (G3PDH) catalyses the formation of sn-glycerol-3-phosphate (G3P) in bacteria and eukarya. The selective enzymatic activity seems to be the main strategy that evolution retained to obtain enantiomeric pure lipids. The occurrence of two genes encoding for G1PDH and G3PDH, served to build up an evolution tree and the basis of our review focusing on the evolution of these two genes. Gene encoding for G3PDH in Eukarya may originate from G3PDH gene found in rare archaea indicating that archaea appeared earlier in the evolution tree than eukarya. Archaea and bacteria evolved probably separately, due to their distinct respective genes coding for G1PDH and G3PDH. The suggested hypothesis is that catalysis of homochiral G1P or G3P from DHAP are more efficient than those leading to racemic G1P and G3P, since there are no enzymes able to synthesize racemic G1P and G3P from DHAP. We propose that G1PDH or G3DPH, which are not “image mirror enzymes” but belonging to distinct family of proteins, emerged separately during evolution. They were probably selected for their efficient catalytic activities during evolution from large libraries of vesicles containing various biopolymers, including amino acids, carbohydrates, nucleic acids, lipids, and meteorite components to induce chemical imbalance.

The tumor organoid (tumoroid) model in three-dimensional (3D) culture systems has been developed to reflect more closely the in vivo tumors than 2D-cultured tumor cells. Notably, extracellular vesicles (EVs) are efficiently collectible from the culture supernatant of gel-free tumoroids. Matrix metalloproteinase (MMP) 3 is a multi-functional factor playing crucial roles in tumor progression. However, roles of MMP3 within tumor growth and EVs have not unveiled. Here, we investigated the protumorigenic roles of MMP3 on integrities of tumoroids and EVs. We generated MMP3-knockout (KO) cells using the CRISPR/Cas9 system from rapidly metastatic LuM1 tumor cells. Moreover, we established fluorescent cell lines with palmitoylation signal-fused fluorescent proteins (tdTomato and enhanced GFP). Then we confirmed the exchange of EVs between cellular populations and tumoroids. LuM1-tumoroids released large EVs (300-1000 nm) and small EVs (50-200 nm) while the knockout of MMP3 resulted in the additional release of broken EVs from tumoroids. The loss of MMP3 leads to a significant reduction in tumoroid size and to the development of the necrotic area within tumoroids. MMP3 and CD9 (a category-1 EV marker tetraspanin protein) were significantly down-regulated in MMP3-KO cells and their EV fraction. These weakened phenotypes by MMP3 KO were markedly rescued by the addition of MMP3-rich EVs or conditioned medium (CM) collected from LuM1-tumoroids, which caused a dramatic rise in the expression of MMP3, CD9, and Ki-67 (a marker of proliferating cells) in the MMP3-null/CD9-low tumoroids. Notably, MMP3 enriched in tumoroids-derived EVs and CM deeply penetrated into recipient MMP3-KO tumoroids, resulting in a remarkable enlargement of solid tumoroids, while MMP3-null EVs did not. These data demonstrate that EVs can mediate molecular transfer of MMP3 resulting in increasing the proliferation and CD9+ tumorigenesis, indicating crucial roles of MMP3 in tumor progression.

Li₂TiO₃ nanopowders were synthesized by hydrothermal process using anatase TiO₂ and LiOH H₂O as raw materials. Li₂TiO₃ crystallizes in the layered monoclinic structure (space group C2/c) with average crystallite size of 34 nm. Morphology, elemental composition and local structure of products were carried out using HRTEM, FESEM, EDS, Raman and FTIR spectroscopy. Transport properties investigated by d.c. (4-probe measurements) and a.c. (complex impedance spectroscopy) show the activation energy of 0.71 and 0.65 eV, respectively. The ionic transport properties of Li⁺ ions in nanocrystalline Li₂TiO₃ characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) validate the good electrochemical properties of this anode material for lithium-ion batteries.

Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathway linked to their proliferation and invasiveness. In particular, ω−3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study 16-(4’-chloro-3’-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω−3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI<0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.

We report here the synthesis and characterization of new N-(3-(8-bromoimidazo[1, 2-a]pyridin-2-yl)-4-fluorophenyl)benzamide derivatives. This collection was obtained from 3-(8-bromoimidazo [1,2-a]pyridin-2-yl)-4-fluoroaniline(5). The family of new compounds was characterized by ¹H-NMR, ¹³C-NMR, FT-IR and LC-MS analysis.

Piezoelectric properties are of significant importance to medical ultrasound, actuators, sensor, and countless other device applications. The mechanism of piezoelectric properties can be deeply understood from structure evolutions. In this paper, we report a diagram of structure evolutions of the Pb(Zn1/3Nb2/3)0.91Ti0.09O3 (PZN-9PT) single crystal with excellent piezoelectric properties among the orthorhombic, tetragonal, and cubic phases with temperature increasing from room temperature to 220 C. Through fitting the temperature dependence XRD curves with Gauss and Lorenz functions, we obtained the evolutions of the content ratio of three kinds of phases (orthorhombic, tetragonal and cubic) and the lattice parameters of the PZN-9PT system with the changes of temperature. The XRD fitting results together with Raman and dielectric spectrums show that the phase transitions of PZN-9PT are a typical continuous evolution process, very similar to the phase transition of paraffin from solid to liquid. Additionally, resonance and anti-resonance spectrum show excellent piezoelectric properties of the crystals, which probably originate from the nano twin domains, as demonstrated by the TEM images. Of particular attention is that the thickness electromechanical coupling factor kt is up to 72%.

Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes of the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction of cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction of Cav1.2-L-type Ca2+ current, mRNA and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3’, 5’-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2- and CREB-mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2- and CREB-mRNA expressions, which were reversed by an ROS scavenger. Our data suggest that EPA rescues cellular remodeling caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.

Background and Aim. Since virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, post-hepatitis C virus (HCV) infection would be a cause for liver cirrhosis that would progress to HCC. Cytotoxic T cells (Tc) are known to be involved in post-HCV complications and HCC pathogenesis. The inhibitory checkpoint Leukocyte-Associated Immunoglobulin-like Receptor-1 (LAIR-1) is expressed on Tc. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression post-HCV and moreover, to evaluate LAIR-1 expression as a non-invasive biomarker for HCC progression in the context of liver cirrhosis post-HCV genotype 4 (G4) in Egyptian patients’ peripheral venous blood liquid biopsy. We studied LAIR-1 expression on Tc related to the progression of liver cirrhosis in a case-controlled study enrolled 64 patients with post-HCV G4-HCC and 37 patients with post-HCV G4-liver cirrhosis. Methods: LAIR-1 expression was analyzed by flow cytometry. Results: LAIR-1 expression on Tc and the percentage of Tc positive for LAIR-1 (LAIR-1+Tc %) were significantly higher in the post-HCV G4-HCC group compared to the post-HCV G4-liver cirrhosis

In this paper, a short survey of the existed results concerning the Jacobian Conjecture is first given. Then the 3-fold linear type polynomial map will be analyzed in detail. The expansion of the Jacobian condition is deduced to obtain its equivalent algebraic equations, and the Jacobian condition will be analyzed to derive two coordinate transformations that can maintain the invariance of the Jacobian condition. Finally, it is proved by mathematical induction method that one general chain expression presented in this paper is just the inverse polynomial map of 3-fold linear type polynomial map, i.e. LJC(n,[3]) holds such that the Jacobian Conjecture holds.

The carbonized elastomer-based composites (CECs) possess a number of attractive features in terms of thermomechanical and electromechanical performance, durability in aggressive media and facile net-shape formability, but their relatively low ductility and strength limit their suitability for structural engineering applications. Prospective applications such as structural elements of MEMS can be envisaged, since smaller principal dimensions reduce the susceptibility of components to residual stress accumulation during carbonization, and to brittle fracture in general. We report the results of operando in-SEM study of micro-deformation and fracture behavior of CECs based on NBR elastomeric matrices filled with carbon and silicon carbide. Nanostructured carbon composite materials were manufactured via compounding of elastomeric substance with carbon and SiC fillers using mixing rolling mill, vulcanization, and low-temperature carbonization. Double Edge Notched Tensile (DENT) specimens of vulcanized and carbonized elastomeric composites were subjected to in situ tensile testing in the chamber of the scanning electron microscope (SEM) Tescan Vega 3 using Deben Microtest 1 kN Tensile Stage. The series of acquired SEM images were analyzed by means of Digital Image Correlation (DIC) using Ncorr open source software to map the spatial distribution of strain. These maps were correlated with Finite Element Modelling (FEM) simulations to refine the values of elastic moduli. Besides, the elastic moduli were derived from unloading curve nanoindentation hardness measurements carried out using NanoScan-4D tester and interpreted using the Oliver-Pharr method. Carbonization causes significant increase of elastic moduli from 0.86 ± 0.07 to 14.12 ± 1.20 GPa for the composite with graphite and carbon black fillers. Nanoindentation measurements yield somewhat lower values, namely, 0.25 ± 0.02 GPa and 9.83 ± 1.10 GPa before and after carbonization respectively. The analysis of fractography images suggests that crack initiation, growth and propagation may occur both at the notch stress concentrator and relatively far from the notch. Possible causes of such response are discussed, namely, (1) residual stresses introduced by processing; (2) shape and size of fillers; and (3) the emanation and accumulation of gases in composites during carbonization.

With the aim to develop novel scaffolds for sustained release of drugs, we initially developed an easy approach for the synthesis of α,ω-homobifunctional mercaptoacyl poly(alkyl oxide)s. This was based on the esterification of the terminal hydroxyl groups of poly(alkyl oxide)s with suitably S-4-methoxytrityl (Mmt) protected mercapto acids, followed by removal of the acid labile S-Mmt group. This method allowed the efficient synthesis of the title compounds in high yield and purity, which were further used in the development a thioether cross-linked liposome scaffold, by thia-Michael reaction of the terminal thiol groups with preformed nano-sized liposomes bearing maleimide groups on their surface. The reaction process was followed by 1H-NMR, using a Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR experiment (1H-NMR CPMG), which allowed real-time monitoring and optimization of the reaction process. The thioether cross-linked liposomal scaffold that was synthesized was proven to preserve the nanosized characteristics of the initial liposomes and allowed sustained release of calcein (which was used as a chromophore), providing evidence for the efficient synthesis of a novel drug release scaffold consisted of nanoliposome building blocks.

Beer is a fermented beverage with a history as old as human civilization and its productive process has been spread all around the world becoming unique in every country and iconic of entire populations. Ales and lagers are by far the most common beers; however, the combination of raw materials, manufacture techniques and aroma profiles are almost infinite, so it is not surprising to notice that there is a large amount of different beer styles, each of them with unique characteristics. Nowadays, diversification is becoming increasingly important in the brewing market and the brewers are continuously interested in improving and extending the already wide range of products, especially in craft brewery. One of the major components that can have a deep impact on the final product is yeast, since it is able to convert carbohydrates in wort, especially maltose and maltotriose, into ethanol, carbon dioxide and other minor aroma-active compounds. Saccharomyces cerevisiae (top‐fermenting yeasts used to produce ales) and Saccharomyces pastorianus (cryotolerant bottom‐fermenting hybrids between S. cerevisiae and Saccharomyces eubayanus responsible for the fermentation of lagers) are most used in breweries. However, an increasing number of different yeast starter cultures are commercially available, to improve the production efficiency also at relative low temperatures and to obtain desirable and diversified aroma profiles avoiding undesired compounds. Four main genetic engineering-free trends are becoming popular in craft brewing yeast development: 1) the research for novel reservoirs as source of new performant S. cerevisiae yeasts; 2) the creation of synthetic hybrids between S. cerevisiae and Saccharomyces non-cerevisiae in order to mimic lager yeasts by expanding their genetic background; 3) the exploitation of evolutionary engineering approaches; 4) the usage of non-Saccharomyces yeasts either in co-coculture or in sequential fermentation with S. cerevisiae. In the present work we summarized pro and contra of these approaches and provided an overview on the most recent advances on how brewing yeast genome evolved and domestication took place. Finally, we delineated how the correlations maps between genotypes and relevant brewing phenotypes can assist and further improve the search for novel craft beer starter yeasts.

Bovine Respiratory Disease Complex, a complex respiratory ailment in cattle, results from a combination of viral and bacterial factors, compounded by environmental stressors such as overcrowding, transportation, and adverse weather conditions. Its impact extends beyond mere health concerns, posing significant economic threats to the cattle industry. This study presents an extensive investigation into viral pathogens associated with BRDC in Serbian cattle, utilizing serum samples and nasal swabs. A cross-sectional study was conducted in 2024 across 65 randomly selected dairy farms in Serbia, excluding vaccinated farms. Farms were categorized by livestock count: small (≤50 animals), medium-sized (51-200 animals), and large (&gt;200 animals). Serum samples from adult cattle older than 24 months were tested for antibodies against BVDV, BHV-1, BRSV, and BPIV3. Nasal swab samples from animals with respiratory signs were tested using PCR for viral genome detection. Results showed seropositivity for all four viruses across all farms, with BPIV3 exhibiting universal seropositivity. Medium-sized and large farms demonstrated higher seropositivity for BRSV and BHV-1 compared to small farms (p&lt;.05). True seroprevalence estimates at the animal level were 84.29% for BRSV, 54.08% for BVDV, 90.61% for BHV-1, and 84.59% for BPIV3. PCR analysis of nasal swabs revealed positive detections for BRSV (20%), BHV-1 (1.7%), BVDV (8%), and BPIV3 (10.9%). Influenza D virus was not found in any of samples. This study provides critical insights into the prevalence and circulation of viral pathogens associated with BRDC in Serbian cattle, emphasizing the importance of surveillance and control measures to mitigate the impact of respiratory diseases in cattle populations.

Our environment has been significantly impacted by man-made pollutants, primarily due to industries make substantial use of synthetic chemicals, resulting in significant environmental consequences. In this research investigation, the co-precipitation approach was employed for the synthesis of cellulose-based ferric oxide (Fe₂O₃/cellulose) and copper oxide nanoparticles (CuOx-NPs). Scanning electron microscopy (SEM) analyses were conducted to determine the properties of the newly synthesised nanoparticles. Furthermore, the synthesized nanoparticles were employed for eliminating chromium from aqueous media under various conditions, including temperature, contact time, adsorbent concentration, adsorbate concentration, and pH. Additionally, the synthesised materials were used to recover Cr(VI) ions from real samples, including tap water, seawater, and industrial water, and the adsorptive capacity of both materials evaluated under optimal conditions. The synthesis of Fe₂O₃/cellulose and CuOx-NPs proved to be effective, as indicated by the outcomes of the study.

Renal uric acid (UA) reabsorption is mainly mediated by urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9). Dotinurad selectively inhibits URAT1 and do not inhibit other UA transporters such as GLUT9, ATP-binding cassette transporter G2 (ABCG2) and organic anion transporter1/3 (OAT1/3). We discovered that dotinurad improved metabolic parameters and renal function in hyperuricemic patients. We consider a significance of high selectivity in inhibiting URAT1 by dotinurad for metabolic syndrome, chronic kidney disease (CKD), and cardiovascular disease (CVD). Dotinurad inhibits selectively URAT1 and increases UA in the proximal tubules, and UA may compete with glucose for GLUT9, reducing glucose reabsorption. The inhibition of UA entry via URAT1 to liver and adipose tissues by dotinurad increased energy expenditure and decrease lipid synthesis and inflammation in rats. The inhibition of URAT1 in kidney, liver and adipose tissues improve metabolic parameters. CKD patients accumulate uremic toxins such as indoxyl sulfate (IS) in the body. ABCG2 regulates renal and intestinal excretion of IS which strongly affects CKD. OAT1/3 inhibitors suppress IS uptake into kidney, increasing plasma IS, which produces oxidative stress, inducing vascular endothelial dysfunction in CKD patients. The high-selective inhibition of URAT1 by dotinurad may be beneficial for metabolic syndrome, CKD and CVD.

Through the use of machine learning algorithms like the Support Vector Machine, it has been show that burn extent can be accurately mapped from hyperspatial drone imagery in both grasslands and forests. Despite these successes, hyperspatial imagery must be acquired via drones, requiring large amounts of time and resources to capture areas much smaller than the large catastrophic fires which result in the majority of the lands burned each year by wildland fires. To overcome this difficulty, high spatial resolution satellite imagery from Worldview2 can be substituted for hyperspatial drone imagery, allowing for larger regions of images to be acquired more easily and efficiently. Additionally, Worldview2 trades spatial resolution for spectral resolution and extent, capturing images in 8 multispectral bands as opposed to 3 band imagery in the visible spectra. This research examines the utility of each of the 8 bands observed in Worldview2 imagery using an Iterative Dichotomiser 3 decision tree, then uses these bands to map burn extent and biomass consumption. Several classifications of burn extent and biomass consumption are produced and compared based on the bands used as inputs. The results show that using Worldview2 imagery to map burn extent and biomass consumption results in highly accurate maps, with slight improvements when additional bands are added.

The collision avoidance mechanism adopted by the IEEE 802.11 standard is not optimal. The mechanism employs a binary exponential backoff (BEB) algorithm in the medium access control (MAC) layer. Such an algorithm increases the backoff interval whenever a collision is detected to minimize the probability of subsequent collisions. However, the expansion of the backoff interval causes degradation of the radio spectrum utilization (i.e., bandwidth wastage). That problem worsens when the network has to manage the channel access to a dense number of stations, leading to a dramatic decrease in network performance. Furthermore, a wrong backoff setting increases the probability of collisions such that the stations experience numerous collisions before achieving the optimal backoff value. Therefore, to mitigate bandwidth wastage and, consequently, maximize the network performance, this work proposes using reinforcement learning (RL) algorithms, namely Deep Q Learning (DQN) and Deep Deterministic Policy Gradient (DDPG), to tackle such an optimization problem. As for the simulations, the NS-3 network simulator is used along with a toolkit known as NS3-gym, which integrates a reinforcement-learning (RL) framework into NS-3. The results demonstrate that DQN and DDPG have much better performance than BEB for static and dynamic scenarios, regardless of the number of stations. Moreover, the performance difference is amplified as the number of stations increases, with DQN and DDPG showing a 27% increase in throughput with 50 stations compared to BEB. Furthermore, DQN and DDPG presented similar performances.

This paper proposes a new structure of the dual-rotor hybrid-excited axial-flux permanent magnet vernier machine (DR-HEAFPMVM) with the modular stator and the consequent-pole PM (CPM) rotor for low-speed, high torque density applications such as in-wheel electric vehicles. The tooth-wound non-overlapping armature windings and direct current (DC) excitation windings are respectively arranged in stator main-teeth and split-teeth to obtain the modulated and adjustable air-gap flux densities, which result in the high torque density and outstanding flux-weakening capability. First, the design consideration, operation principle, and the air-gap flux density distributions of the proposed machine are elaborated based on the air-gap permeance function. Then, the influence of the pole ratios (PRs) and the DC excitation currents on the main electromagnetic performances of the DR-HEAFPMVM, such as the flux-weakening capability, back-electromotive force (back-EMF), on-load electromagnetic torque, loss distribution, and efficiencies, is investigated using the 3-D finite-element method (FEM). Results verify the feasibility of the flux adjustment of the DC excitation windings equipped in the split-tooth, and the design with a pole ratio of 8/1 tends to have higher torque density, higher machine efficiency, and considerable flux-weakening capability compared with the other two PRs.

Dendrobium okinawense is an endangered epiphytic orchid, and there has been no scientific report so far on its propagation. Protocorm is mass of cell, and protocorm-like bodies (PLBs) look alike protocorm produced by vegetative explants in vitro. Regeneration of PLBs is the most efficient technique for the orchids micro-propagation. We used different light emitting diodes (LEDs) for the efficient PLB organogenesis of D. okinawense. PLBs regenartion under green and red LED surpassed respectively 81.1% and 71.6% in numbers, and respectively 80.8% and 57.8% in fresh weight over white fluorescent light. We manipulated the culture media by different concentrations of PCIB and HMI. PLBs organogenesis promoted by low concentration, it increased respectively 35.9% and 19.3% over control by 0.01 mg/L PCIB and 0.01 ml/L HMI in numbers. Green LED and PCIB independently produced mostly similar numbers of new PLBs. Interestingly, culture media with 0.01 mg/L of PCIB further increased 8.5% of the numbers of PLBs under green LED, whereas the culture media with 0.01 mg/L HMI reduced the number of PLBs under green LED. PLBs culture under green LED with very low concentrations of PCIB manipulated culture media can significantly increase their organogenesis of D. okinawense.

The goal of newborn screening is to improve health outcomes by identifying and treating affected newborns. This manuscript provides an overview of a data tool to facilitate the longitudinal collection of health information on newborns diagnosed with a condition through NBS. The Newborn Screening Translational Research Network (NBSTRN) developed the Longitudinal Pediatric Data Resource (LPDR) to capture, store, analyze, visualize, and share genomic and phenotypic data over the lifespan of NBS identified newborns to facilitate understanding of genetic disease, and to assess the impact of early identification and treatment. NBSTRN developed a consensus-based process using clinical care experts to create, maintain, and evolve question and answer sets organized into common data elements (CDEs). The LPDR contains 24,172 core and disease-specific CDEs for 118 rare genetic diseases, and the CDEs are being made available through the NIH CDE Repository. The number of CDEs for each condition average of 2,200 with a range from 69 to 7,944. The LPDR is used by state NBS programs, clinical researchers, and community-based organizations. Case level, de-identified data sets are available for secondary research and data mining. The development of the LPDR for longitudinal data gathering, sharing, and analysis supports research and facilitates the translation of new discoveries into clinical practice.

Within the scope of observed materialistic physical systems, without addressing the roots of H-Bar and big G, it is impossible to construct a workable model of final unification. With reference to our earlier proposed three large atomic gravitational constants, it is possible to reform and compactify the 10 dimensional String theory to 3+1 dimensions

Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and in particular the interferon response form the important first line of defense against these viruses. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity. Already many molecular mechanisms of innate immune evasion by +ssRNA viruses have been identified. However, research addressing the effect of host innate immune evasion on the pathology caused by the viral infection is less prevalent in literature, though very relevant and interesting. Since interferons have been implicated in inflammatory diseases and immunopathology in addition to their protective role in infection, the influence of antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. Therefore, this review discusses what is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging viruses belonging to the coronaviruses, alphaviruses and flaviviruses.

The noble metals palladium and silver find use in many high performance applications, and their alloys (PdAg), known for more than sixty years, are industrially important, finding use in many fields including hydrogen purification and separation, numerous facets of catalysis, and in fuel cells. In recent years, interest in these materials has grown significantly, particularly in energy generating applications and due to their performance as solid-state chemical sensors for a range of small molecules. PdAg thin films can be prepared using traditional physical methods such as cold rolling, or more modern and controllable chemical or physical deposition techniques such as electrodeposition or chemical vapour deposition. Despite the wide-reaching uses of PdAg, several recent advancements in materials preparation, such as additive manufacturing, better known as 3-D printing, remain unexplored for this material due to the differing chemistries of the two elements. In this review, we explore the manufacturing methods commonly employed for the preparation of PdAg thin films, the common and niche applications of these materials, and opportunities for the future development of these two aspects, with an emphasis on how preparation of thin films can utilise additive manufacturing approaches.

Compounds with tyrosinase inhibitory efficacy could be effective as depigmenting agents. Although a large number of natural and synthetic tyrosinase inhibitors have been reported, few of them are used as skin-whitening agents due to poor activity and safety concerns. 3-(2,4-Dihydroxyphenyl)propionic acid (DPPA), a naturally occurring compound isolated from Ficus carica, was previously discovered as a moderate tyrosinase inhibitor. In this study, the structure-activity relationship study of DPPA was conducted. Compound 3g, with the 2,4-resorcinol subunit and terminal hydrophobic di-butylamino group, was identified with low nanomolar enzymatic IC₅₀ value. Additionally, compound 3g could effectively reduce melanin levels in B16-F10 melanoma cells treated with α-melanocyte-stimulating hormone (α-MSH) without affecting cell viability and proliferation. All these results indicated that compound 3g could be considered as a promising candidate for the treatment of diseases associated with hyperpigmentation.

Although distributed additive manufacturing can provide high returns on investment the current markup on commercial filament over base polymers limits deployment. These cost barriers can be surmounted by eliminating the entire process of fusing filament by 3-D printing products directly from polymer granules. Fused granular fabrication (FGF) (or fused particle fabrication (FPF)) is being held back in part by the accessibility of low-cost pelletizers and choppers. An open-source 3-D printable invention disclosed here provides for precise controlled pelletizing of both single thermopolymers as well as composites for 3-D printing. The system is designed, built and tested for its ability to provide high tolerance thermopolymer pellets from a number of sizes capable of being used in a FGF printer. In addition, the chopping pelletizer is tested for its ability to chop multi-materials simultaneously for color mixing and composite fabrication as well as precise fractional measuring back to filament. The US$185 open-source 3-D printable pelletizer chopper system was successfully fabricated and has a 0.5 kg/hr throughput with one motor, and 1.0 kg/hr throughput with two motors using only 0.24 kWh/kg during the chopping process. Pellets were successfully printed directly via FGF and indirectly after being converted into high-tolerance filament in a recyclebot.

Pleural mesothelioma (PM) comprises three main subtypes: epithelioid, biphasic and sarcomatoid, which have a different impact on prognosis and treatment definition. However, PM subtyping can be complex given the inter- and intra-tumour morphological heterogeneity. We aim to use immunohistochemistry (IHC) to evaluate five markers (Mesothelin, Claudin-15, Complement Factor B, Plasminogen Activator Inhibitor 1, and p21-activated Kinase 4), whose encoding genes have been previously reported as deregulated among PM subtypes. Immunohistochemical expressions were determined in a case series of 73 PMs, and cut-offs for the epithelioid and non-epithelioid subtypes were selected. Further validation was performed on an independent cohort (30 PMs). For biphasic PM, the percentage of the epithelioid component was assessed, and IHC evaluation was also performed on the individual components separately. Mesothelin and Claudin-15 showed a good sensitivity (79% and 84%) and specificity (84% and 73%) for the epithelioid subtype. CFB and PAK4 had an inferior performance, with higher sensitivity (89% and 84%), but lower specificity (64% and 36%). In the biphasic group, all markers showed a different expression when comparing epithelioid with sarcomatoid areas. Mesothelin, Claudin-15 and CFB can be useful in subtype discrimination. PAI1 and PAK4 can improve component distinction in biphasic PM.

The electronic structure and the participation of the simplest azomethine imine (AI) in [3+2] cycloaddition (32CA) reactions have been analysed within the Molecular Electron Density Theory (MEDT) using DFT calculations at the MPWB1K/6-311G(d) level. Electron localisation function (ELF) topological analysis reveals that AI has a pseudoradical structure, while the conceptual DFT reactivity indices characterise this TAC as a moderate electrophile and a good nucleophile. The non-polar 32CA reaction of AI with ethylene takes place through a one-step mechanism with low activation energy, 5.3 kcal/mol-1. A bonding evolution theory (BET) study indicates that this reaction takes place through a non-concerted [2n+2τ] mechanism in which the C–C bond formation is clearly anticipated prior to the C–N one. On the other hand, the polar 32CA reaction of AI with dicyanoethylene takes place through a two-stage one-step mechanism. Now, the more favourable regioisomeric transition state structure (TS) is located 8.5 kcal•mol⁻¹ below the reagents, in complete agreement with the high polar character of the TS. The current MEDT study makes it possible to extend Domingo’s classification of 32CA reactions to a new pra-type of reactivity.

Through the use of Smart Sensor Networks (SSN), Marine Observatories (MO) provide continuous ocean monitoring. Deployed sensors may not perform as intended due to the heterogeneity of SSN devices’ hardware and software when combined with the Internet. Hence, SSN are regarded as complex distributed systems. As such, SSN designers will encounter challenges throughout the design phase related to time, complexity, sharing diverse domain experiences (viewpoints), and ensuring optimal performance for the deployed SSN. To this end, we describe in this article how we extended our previously proposed ArchiMO meta-model and design tool by extending an Enterprise Architecture Framework based on the ArchiMate Modeling Language. This extension proposes the incorporation of new Underwater Environmental Constraints (UEC) for SSN in ArchiMO which is coupled with the fusion of sensors with Artificial Intelligence. This serves as the basis for generating a new version of our ArchiMO design tool, which incorporates the new added constraints and invokes the AI created Database. To illustrate our proposal, we use the newly generated ArchiMO to create a model in the MO domain. Furthermore, we use our self-developed domain-specific model compiler to produce the relevant simulation code. Throughout the design phase, our approach contributes to handle and control the uncertainties and variances of the provided quality of service that may occur during the performance of the SSN, hence reducing the design activity’s complexity and time. It provides a way to share the different viewpoints of the designers in the domain of SSN.

Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the GH receptor (GHR) gene, which is the main factor influencing human development and is essential to optimal functioning of the GH/IGF-I axis. Two GHR isoforms have been studied, according to the presence (flGHR) or absence (d3GHR) of exon 3. The d3GHR variant, which has recently been related to longevity, is associated with enhanced signal transduction and higher receptor function. Many of these studies indicated that the growth response to GH treatment may be affected. Individuals carrying the d3GHR isoform have higher receptor activity, improved signal transduction, and alterations in the treatment response and efficacy compared with those carrying the WT isoform. Further, studies performed in patients with acromegaly, Prader-Willi syndrome, Turner syndrome, small for gestational age (SGA), and growth hormone deficiency (GHD) suggested that the d3GHR variant may have an impact on the relationship between GH and IGF-I levels, height, weight, BMI, and other variables. Other research, however, revealed inconsistent results, which might have been caused by confounding factors, including limited sample sizes and different experimental methods. In this review, we lay out the complexity of the GHR isoforms and provide an overview of the major pharmacogenetic research conducted on this ongoing and unresolved subject.

This paper examines the potential of Artificial Intelligence (AI) to address societal megatrends, with a specific focus on OpenAI’s Generative Pre-Trained Transformer 3 (GPT-3). To do this, we con-ducted an analysis using GPT-3 in order to explore the benefits of AI for digitalization, urbanization, globalization, climate change, automation and mobility, global health issues and aging population. We also looked at emerging markets as well as sustainability in this study. Interaction with GPT-3 was done solely through prompt questions and generated responses were analyzed. Our results indicate that AI can significantly improve our understanding of these trends by providing insights into how they develop over time and what solutions could be implemented. Further research is needed to determine how effective AI will be in addressing them successfully but initial findings are encouraging. Our discussion focuses on the implications of our findings for society going forward and suggests that further investigation should be done into how best to utilize new technologies like GPT-3 when tackling these challenges. Lastly, we conclude that while there is still much work left to do before any tangible effects can be seen from utilizing AI tools such as GPT-3 on societal mega-trends; early indications suggest it may have a positive impact if used correctly.

During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although, the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural-functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA to support the optimal brain development and growth and functional roles in the brain.

Public health practices including handwashing and vaccinations help reduce the spread and impact of infections. Nevertheless, the global burden of infection is high, and additional measures are necessary. Acute respiratory tract infections, for example, are responsible for approximately 2.65 million deaths per year. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: 1) Supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function; 2) Supplementation above the RDA, but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and 3) Public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

Zebrafish have been found to be the premier model organism in biological and biomedical research, specifically offering many advantages in developmental biology and genetics. This unique aquatic species has been found to have the capacity to regenerate their spinal cord after injury. However, the complete molecular and cellular mechanisms behind glial bridge formation in the central and peripheral nervous systems upon glial cell injury remains unclear. This review paper focuses on the molecular mechanisms and cellular processes that underlie spinal cord regeneration in four initial phases: proliferation and initial migration; migration and differentiation; glial bridge formation; and remodeling. We propose that within these four phases the cellular mechanisms that underlie spinal cord regeneration each express a terminating signal that aborts one step of the process and initiates the next. Specifically, future studies would be devoted to investigate transmitting signals in the spinal cord injury micro-environment in hope to contribute to the understanding of underlying cellular mechanisms by connecting each process of spinal cord regeneration in zebrafish.

Transient receptor potential melastatin-8 (TRPM8) is a cation channel that is activated by cold and “cooling agents” such as menthol and icilin, which induce a cold sensation. Stimulation of TRPM8 activates an intracellular signaling cascade that ultimately leads to a change in the gene expression pattern of the cells. Here, we investigated the TRPM8-induced signaling pathway that links TRPM8 channel activation to gene transcription. Using a pharmacological approach, we show that inhibition of phosphatidylinositol 4-phosphate 5 kinase alpha (PIP5K), an enzyme essential for the biosynthesis of phosphatidylinositol 4,5-bisphosphate, attenuated TRPM8-induced gene transcription. Analyzing the link between TRPM8 and Gq proteins, we show that pharmacological inhibition of the beta gamma subunits impairs TRPM8 signaling. In addition, genetic studies showed that TRPM8 requires an activated Galpha subunit for signaling. In the nucleus, the TRPM8-induced signaling cascade triggers an activation of the transcription factor AP-1, a complex consisting of a dimer of basic region leucine zipper (bZIP) transcription factors. Here, we identified the bZIP protein c-Jun as an essential component of AP-1 within the TRPM8-induced signling cscade. In summary, with PIP5K, Gq subunits and c-Jun we have identified key molecules in the TRPM8-induced signaling from the plasma membrane to the nucleus.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, wings, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects and all other arthropods. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. As a means of renaming this protein family, this review article discusses the latest findings (“CSP” is attached to the tail of bigger intracellular proteins) and attempts to compel all the data. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins) and use at least for abbreviations for distinctive animal proteins the common peptide 5-letter code, such as “Bommo-4CSPs”.

Space-time evolution is briefly explained by using the 3-dimensional quantized space model (TQSM) based on the 4-dimensional (4-D) Euclidean space. The energy (mass), charges and absolute time are newly defined based on the 4-D Euclidean space. The photons and gravitons are understood as the 2-D space fluctuations along the space axes and 1-D time fluctuations along the time axis, respectively. This indicates that the electromagnetic (EM) and gravitational (G) waves can be unified into the so called gravityelectromagnetic (GEM) wave which has both space and time fluctuations. The photon with zero force fields is the 2EM wave because an EM wave corresponds to a charged fermion. The dark matter bosons, weak force bosons, strong force bosons are the 1-D time fluctuations which can be expressed by the G waves. This indicates that all five forces are unified by the GEM wave. It is called as the super unification theory in the present work. And the force carrying bosons and mesons are, for the first time, proposed as the possible candidates of the magnetic monopoles like the fermions and baryons are the electric monopoles. The signs of the magnetic charges quantized as q_m=cq are newly defined. The big bang is understood by the space-time evolution of the 4-D Euclidean space but not by the sudden 4-D Minkowski space-time creation. The big bang process created the matter universe with the positive energy and the partner anti-matter universe with the negative energy from the CPT symmetry.

Nutrition, diabetes, and mental disorders are interconnected and significantly impact an individual's overall health and well-being. This comprehensive review aims to explore the complex interplay between nutrition, diabetes, and mental disorders, highlighting the latest research findings in this field. While the influence of nutrition on the development and management of both diabetes and mental disorders is widely recognized, there remains a gap in understanding the intricate interplay between nutrition, mental health, and diabetes. Diabetes is associated with an increased risk of mental disorders, including depression, anxiety, and cognitive decline. Mental disorders can also contribute to the development of diabetes through various mechanisms including increased stress, poor self-care behaviors, and adverse effects on glucose metabolism. Thus, the mechanisms linking nutrition, diabetes, and mental disorders are complex and multi-factorial. Inflammation, oxidative stress, gut microbiota alterations, and neuroendocrine dysregulation have emerged as potential pathways that may mediate the relationship between nutrition, diabetes, and mental disorders. Additionally, deficiencies in essential nutrients such as omega-3 fatty acids, vitamin D, B vitamins, zinc, chromium, magnesium, and selenium have been implicated in the pathogenesis of both diabetes and mental disorders. Our findings indicate that the use of personalized dietary interventions and targeted nutrient supplementation can improve metabolic and mental health outcomes in patients with type 2 diabetes.

Mitochondrial pyruvate dehydrogenase complex (PDHC) is essential for the brain glucose and neurotransmitter metabolism, dysregulated in many pathologies. Using specific inhibitors of PDHC in vivo, we determine biochemical and physiological responses to PDHC dysfunction. Dose dependence of the responses to membrane-permeable dimethyl acetylphosphonate (Ac-PMe2) is non-monotonous. Primary decreases in glutathione and its redox potential, methionine and ethanolamine are alleviated with increasing PDHC inhibition, the alleviation accompanied by physiological changes. Comparison of 39 brain biochemical parameters after administration of four phosphinate and phosphonate analogs of pyruvate at a fixed dose of 0.1 mmol/kg reveals no primary, but the secondary changes, such as activation of 2-oxoglutarate dehydrogenase complex (OGDHC) and decreased levels of glutamate, isoleucine and leucine. The accompanying decreases in RMSSD of ECG and freezing time are most pronounced after administration of me-thyl acetylphosphinate and dimethyl acetylphosphonate. The levels of PDHA1 expression and phosphorylation, sirtuin 3 and total protein acetylation are not significantly changed by the PDHC inhibitors that affect the brain protein succinylation and glutarylation. Thus, decreased production of the tricarboxylic acid cycle substrate acetyl-CoA by inhibited PDHC is compen-sated by increased degradation of amino acids through the cycle with activated OGDHC, increas-ing total protein succinylation and decreasing anxiety indicators.

This study continued the analysis of immunization with the receptor binding domain (RBD) associated with the adjuvants Dimethyldioctadecylammonium bromide (DDA) and Saponin (Sap) (RBD+DDA/Sap) or Aluminum hydroxide (AH) and outer membrane vesicles (OMVs) of Neisseria meningitidis (RBD+AH/OMV); from adult to old age and assessed maternal-fetal transference of antibodies. Outbred Swiss mice were immunized with 2 intramuscular (IM) doses with the antigenic preparations RBD+DDA/Sap, RBD+AH/OMV or RBD alone. The humoral immune response was evaluated using ELISA, avidity-ELISA, Immunoblotting and a Omicron-surrogate-neutralization assay (BA.1), while the cellular immune response was analyzed by ELISpot. Our previous work studied the IgG response; here, we verified that IgM levels were higher right after the immunization doses, but, as IgG, it persisted until 368 days after the immunization. The avidity of IgM increased from low to intermediate-to-high after the booster dose. RBD+DDA/Sap presented neutralizing indexes against Omicron at days 47 and 176, while RBD+AH/OMV showed neutralization on days 21, 47 and 176. Cellular response, measured 465 days after immunization, revealed IFN-Y and IL-4 secretion. The offspring of RBD+DDA/Sap had detectable antibodies, which decreased around 45 days after birth, the last point we analyzed. The results suggested that DDA/Sap is a promising adjuvant mixture to enhance humoral and cellular immune response against SARS-CoV-2, improving maternal-fetal transference of antibodies; cross-reactivity with Omicron variant; and the maintenance of antibodies for a long period.

Lake ice thickness (LIT) is a sensitive indicator of climate change identified as a thematic variable of Lakes as an Essential Climate Variable (ECV) by the Global Climate Observing System (GCOS). Here, we present a novel and efficient analytically based retracking approach for estimating LIT from high-resolution Ku-band (13.6 GHz) synthetic aperture radar (SAR) altimetry data. The retracker method is based on the analytical modeling of the SAR radar echoes over ice-covered lakes that show a characteristic double-peak feature attributed to the reflection of the Ku-band radar waves at the snow-ice and ice-water interfaces. The method is applied to Sentinel-6 Unfocused SAR (UFSAR) and Fully Focused SAR (FFSAR) data, with their corresponding tailored waveform model, referred to as the SAR_LITand FFSAR_LITretracker, respectively. LIT retrievals from Sentinel-6 SAR data at different posting rates are evaluated against those obtained from thermodynamic lake ice model simulations and Low Resolution Mode (LRM) Sentinel-6 and Jason-3 data over two ice seasons during the tandem phase of the two satellites, allowing precise assessment of the continuity between LRM and SAR LIT retrievals. Consistency checks of the Sentinel-6 SAR LIT estimates are also performed using optical/radar images that provide information on the snow/ice conditions on the same dates. The analysis is performed on Great Slave Lake and Baker Lake (Canada) that differ in terms of lake size, bathymetry, snow/ice properties, and seasonal evolution of LIT. The accuracy of the LIT estimates with the SAR LIT retrackers is on the order of 5 cm once the ice is well established on the lakes, meeting the GCOS requirements of LIT measurement uncertainty, which is a factor of 2 to 3 times better than that of LIT obtained with LRM data, bringing a further improvement compared to previous analyses and methods. The SAR LIT retrackers presented are promising tools for monitoring the inter-annual variability and trends in LIT from current and future SAR altimetry missions.

SRC homology 3 (SH3) domains are critical interaction modules that orchestrate the assembly of protein complexes involved in diverse biological processes. They facilitate transient protein-protein interactions by selectively interacting with proline-rich motifs (PRMs). A database search revealed 298 SH3 domains in 221 human proteins. Multiple sequence alignment of human SH3 domains is useful for phylogenetic analysis and determination of their selectivity towards PRM-containing peptides (PRPs). However, a more precise functional classification of SH3 domains is achieved by constructing a phylogenetic tree only from PRM-binding residues and using existing SH3-PRP structures and biochemical data to determine the specificity within each of the 10 families for particular PRPs. In addition, the C-terminal proline-rich domain of the RAS activator SOS1 covers 13 of the 14 recognized proline-rich consensus sequence motifs, encompassing differential PRP pattern selectivity among all SH3 families. To evaluate binding capabilities and affinities, we conducted fluorescence dot blot and polarization experiments using 25 representative SH3 domains and various PRPs derived from SOS1. Our analysis has identified 45 interacting pairs with binding affinities ranging from 0.2 to 125 micromolar out of 300 tested and potential new interactors of SOS1. Furthermore, it establishes a framework to bridge the gap between SH3 and PRP interactions and provides predictive insights into potential interactions of SH3 domains with PRMs based on sequence specifications. This novel framework has the potential to enhance the understanding of protein networks mediated by SH3-PRM interactions and be utilized as a general approach for other domain-peptide interactions.

As variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, assessment of vaccine immunogenicity remains a critical factor to support continued vaccination. To this end, an in vitro microneutralization (MN50) assay was validated to quantitate SARS-CoV-2 neutralizing antibodies against ancestral and variant strains (Beta, Delta, Omicron BA.1, Omicron BA.5 and XBB.1.5) in human serum. For ancestral strain, the MN50 assay met acceptance criteria for inter-/intra-assay precision, specificity, linearity, and selectivity. The assay was robust against changes to virus/serum incubation time, cell seeding density, virus content per well, cell passage number, and serum interference. Analyte in serum samples was stable up to 5 freeze/thaw cycles and for up to 12 months of storage at –80 ± 10 °C. Similar results were observed for the variant-adapted MN50 assays. The conversion factor to convert assay result units to WHO international standard units (IU/mL) was determined to be 0.62 for the ancestral prototype strain. This MN50 assay will be useful for vaccine immunogenicity analyses in clinical trial samples, enabling assessment of vaccine immunogenicity for ancestral and variant strains as variant-adapted vaccines are developed.

Artificial Intelligence (AI) experienced significant advancements in recent years, and its impact is already recognized across various industries. Yet, the rise of AI has led to a growing concern about its impact on meeting the Sustainable Development Goals (SDGs). The aim of this paper was to evaluate contributions and the potential impact of AI to sustainable development in the society domain. Furthermore, the study analyzed GPT-3 responses, as one of the largest language models developed by OpenAI, descriptively. We conducted a set of queries on the SDGs to gather infor-mation on GPT-3`s perceptions of AI impact on sustainable development. Analysis of GPT-3’s contribution potential towards the SDGs showcased its broad range of capabilities for contributing to the SDGs in areas such as education, health, and communication. The study findings provide valuable insights into the contributions of AI to sustainable development in the society domain and highlight the importance of proper regulations to promote the responsible use of AI for sustainable development. We plan subsequent research for effects on ecologic and economic domains of SDGs. We highlighted the potential for improvement in neural language processing skills of GPT-3 by avoiding imitating weak human writing styles with more mistakes in longer texts.

Maternal intake of the polyunsaturated fatty acids omega-3 (n-3 PUFA) and omega-6 (n-6 PUFA) impacts hippocampal neurogenesis during development, an effect that may extend to adulthood by altering adult hippocampal neurogenesis (AHN). n-3 PUFA and n-6 PUFA are precursors of inflammatory regulators that potentially affect AHN and glia. Additionally, n-3 PUFA dietary supplementation may present a sexually dimorphic action in the brain. Therefore, we postulated that dietary n-6/n-3 PUFA balance shapes the adult DG in a sex-dependent manner influencing AHN and glia. We test our hypothesis by feeding adult female and male mice with n-3 PUFA balanced or deficient diets. To analyze the immunomodulatory potential of the diets, we injected mice with the bacterial endotoxin lipopolysaccharide (LPS). LPS reduced neuroblast number, and its effect was exacerbated by the n-3 PUFA deficient diet. The n-3 PUFA deficient diet reduced the DG volume, AHN, microglia number and surveilled volume. Diet effect on most mature neuroblasts was exclusively significant in female mice. Colocalization and multivariate analysis revealed an association between microglia and AHN, and the sexual dimorphic effect of diet. Our study reveals that female mice are more susceptible than males to the effect of dietary n-6/n-3 PUFA ratio on AHN and microglia.

Access to nasopharyngeal swabs for sampling remain a bottleneck in some regions for COVID-19 testing. This study develops a distributed manufacturing solution using only an open source manufacturing tool chain consisting of two types of open source 3-D printing and batch UV curing, and provides a parametric fully free design of a nasopharyngeal swab. The swab was designed using parametric OpenSCAD in two components (a head with engineered break point and various handles), which has several advantages: i) minimizing print time on relatively slow SLA printers, ii) enabling the use of smaller print volume open source SLA printers, iii) reducing the amount of relatively expensive UV resin, and iv) enabling production of handle on more accessible material extrusion 3-D printers. A modular open source UV LED box was designed, fabricated for $45 and tested for batch curing. Swabs can be fabricated for $0.06-$0.12/swab. The results of the mechanical validation tests showed that the swabs could withstand greater forces than would be expected in normal clinical use. The swabs were also able to absorb a significant amounts of synthetic mucus materials and passed abrasion and handling tests. The results show the open source swab are promising candidates for clinical trials.

This study provides designs for a low-cost, easily replicable open source lab-grade digital scale that can be used as a precision balance. The design is such that it can be manufactured for use in most labs throughout the world with open source RepRap-class material extrusion-based 3-D printers for the mechanical components and readily available open source electronics including the Arduino Nano. Several versions of the design were fabricated and tested for precision and accuracy for a range of load cells. The results showed the open source scale was found to be repeatable within 0.1g with multiple load cells, with even better precision (0.01g) depending on load cell range and style. The scale tracks linearly with proprietary lab-grade scales, meeting the performance specified in the load cell data sheets, indicating that it is accurate across the range of the load cell installed. The smallest loadcell tested(100g) offers precision on the order of a commercial digital mass balance. The scale can be produced at significant cost savings compared to scales of comparable range and precision when serial capability is present. The cost savings increase significantly as the range of the scale increases and are particularly well-suited for resource-constrained medical and scientific facilities.

The term neurodegeneration with brain iron accumulation (NBIA) brings together a broad set of progressive and disabling neurological genetic disorders in which iron is deposited preferentially in certain areas of the brain. Among NBIA disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by pathologic variants in the PANK2 gene codifying the enzyme pantothenate kinase 2 (PANK2). Nowadays, there are no effective treatments to stop the progression of these diseases. This review discusses the utility of patient-derived cell models as a valuable tool for the identification of commercial pharmacological or natural compounds for implementing polytarget precision medicine in PKAN. In the last years, several studies have described that PKAN patient-derived fibroblasts manifest the main pathological changes associated with the disease including intracellular iron overload. Interestingly, treatment of mutant cell cultures with various supplements such as pantothenate, pantethine, thiamine, L-carnitine, vitamin E, omega 3, and -lipoic acid improved all pathophysiological alterations in PKAN fibroblasts with residual expression of the PANK2 enzyme. The information provided by pharmacological screenings in patient-derived cellular models can help to optimize therapeutic strategies in individual PKAN patients.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. This article tries to compel and discuss the most recent information as a way to rename this protein family. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins).

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but severe adverse event that was first observed during the global vaccination campaign against SARS-CoV-2 infection, specifically in those receiving adenoviral vector-based vaccines for Coronavirus disease 2019 (COVID-19). VITT develops 4 to 42 days post-vaccination and is characterized by the development of platelet-activating anti-platelet factor 4 (PF4) antibodies, leading to thrombocytopenia and thrombosis at unusual sites. The rise in awareness and subsequent prompt recognition of VITT was paramount in reducing mortality. Moreover, as vaccination campaigns around the world continue, a better understanding of VITT not only has important clinical implications but is also crucial for future vaccine development. In this review, we summarize the clinical features, pathophysiology, and incidence rates of VITT as well as highlight other anti-PF4 antibody-mediated disorders of growing clinical significance.

Effective therapeutics for Alzheimer's disease (AD) are in great demand worldwide. In our previous work, we responded to this need by synthesizing novel drug candidates consisting of 4-amino-2,3-polymethylenequinolines conjugated with butylated hydroxytoluene via fixed-length alkylimine or alkylamine linkers (spacers) and studying their bioactivities pertaining to AD treatment. Here, we report significant extensions of these studies, including the use of variable-length spacers and more detailed biological characterizations. Conjugates were potent inhibitors of acetylcholinesterase (AChE, minimum IC50 15.1±0.2 nM) and butyrylcholinesterase (BChE, minimum IC50 5.96±0.58 nM), with weak inhibition of off-target carboxylesterase. Conjugates with alkylamine spacers were more effective cholinesterase inhibitors than alkylimine analogs. Optimal inhibition for AChE was exhibited by cyclohexaquinoline and for BChE by cycloheptaquinoline. Increasing spacer length elevated potency against both cholinesterases. Structure-activity relationships agreed with docking results. Mixed-type reversible AChE inhibition, dual docking to catalytic and peripheral anionic sites, and propidium iodide displacement suggested the potential of hybrids to block AChE-induced β-amyloid (Aβ) aggregation. Hybrids also exhibited inhibition of Aβ self-aggregation in the thioflavin test; those with a hexaquinoline ring and C8 spacer were the most active. Conjugates demonstrated high antioxidant activity in ABTS and FRAP assays as well as inhibition of luminol chemiluminescence and lipid peroxidation in mouse brain homogenates. Quantum-chemical calculations explained antioxidant results. Computed ADMET profiles indicated favorable blood-brain barrier permeability suggesting CNS activity potential. Thus, the conjugates could be considered promising multifunctional agents for potential treatment of AD.

The complete regression of clear cell renal cell carcinoma (ccRCC) obtained pre-clinically with anti-carbonic anhydrase IX (CAIX) G36 chimeric antigen receptor (CAR) T cells in doses equivalent to 10e8 CAR T cells/ Kg renewed the potential of this target to treat ccRCC and other tumors in hypoxia. The immune checkpoint blockade (ICB) brought durable clinical responses in advanced ccRCC and other tumors. Here we tested CD8/4-1BB compared to CD28-based anti-CAIX CAR PBMCs cells-releasing anti-programmed cell death ligand-1 (PD-L1) IgG4 for human ccRCC treatment in vitro and in an orthotopic NSG mice model in vivo. Using a 10e7 CAR PBMCs cells/ Kg dose, anti-CAIX CD28 CAR T cells releasing anti-PD-L1 IgG highly decrease both tumor volume and weight in vivo, avoiding the occurrence of metastasis. This antitumoral superiority of CD28-based CAR PBMCs cells compared to 4-1BB occurred under ICB via PD-L1. Furthermore, T cell exhaustion status in peripheral CD4 T cells, additionally to CD8 was critical for CAR T cells efficiency. The lack of hepatotoxicity and nephrotoxicity upon administration of 10e7 CAR PMBCs cells/Kg dose is the basis for carrying out clinical trials using anti-CAIX CD28 CAR PBMCs cells releasing anti-PD-L1 antibodies or anti-CAIX 4-1BB CAR T cells, offering exciting new prospects for the treatment of refractory ccRCC and hypoxic tumors.

The thermoelectric generator (TEG) has much potential as a renewable energy technology that could be used in ocean thermal energy conversion (OTEC). This technique employs TEGs and heat exchangers as substitutes for the intricate elements found in conventional OTEC systems, including pressure valves, evaporators, condensers, and turbine generators. By harnessing the temperature difference between warm surface seawater and cold deep seawater, it facilitates the conversion of this thermal gradient into electrical energy. This study used computer simulations to look at and compare three different types of heat exchangers: a cavity-type heat exchanger, a heat exchanger with flat fins, and a heat exchanger with longitudinal vortex generators (LVGs). The objective was to evaluate the influence of these designs on the thermoelectric conversion performance when implemented in OTEC systems. The study's findings indicate that using heat exchanger configurations featuring flat fins, or LVGs, enhances the efficiency of thermal energy transfer from warm seawater to TEGs, resulting in a notable enhancement in the output power of TEGs. Furthermore, the efficiency of TEG thermoelectric conversion is influenced by varying seawater flow rates in relation to the performance of flat fins and LVGs. In contrast to the cavity-type heat exchanger, the utilization of a heat exchanger equipped with flat fins has been found to yield a notable enhancement in the output power of TEGs by approximately 22.92%. Furthermore, this configuration demonstrates a substantial improvement in thermoelectric conversion efficiency, exhibiting an increase of around 40.01%. These improvements are observed under certain conditions pertaining to flow rates and fin heights. Utilizing heat exchangers equipped with LVGs has been found to enhance the output power of TEGs by 13.02% and improve the overall thermoelectric conversion efficiency by 17.72%. These improvements are observed under certain conditions, including specific flow rates, LVG tilt angles, and locations.