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Motile aeromonads are an opportunistic and heterogenic bacteria that cause motile Aeromonas septicemia (MAS) which is accompanied with variety of clinical signs and lesions in fish. It has been found that their outer membrane proteins (OMPs) are highly immunogenic and may be used as a vaccine candidate. The present study was undertaken to evaluate OMP protection against Aeromonas hydrophila (A. hydrophila) strain ATCC 7966 (A5 and A8) and A. hydrophila strain DSM 30,187 (A6). Pathogenicity tests revealed that out of 12 isolated strains, seven were highly pathogenic, three were moderate, and two were avirulent. SDS-PAGE analysis of OMPs showed several protein bands (7–22) of different molecular weights ranging from 14 to 346 kDa. The common protein band was 39 kDa. It seems that pathogenicity and the number of protein bands are related in the highly pathogenic strains. Challenged A. hydrophila for Nile tilapia (O. niloticus) previously actively immunized with OMPs (A4, A5, A6, A8, and A11) showed a significant increase in relative percent survival (RPS) ranging from 50 to 100%. Immunological parameters such as immunoglobulin M (IgM), antioxidants (SOD, GSH, and CAT), and nitric oxide (NO) and expression of pro-inflammatory cytokines, interleukin 1β (IL-1β), and tumor necrosis factor-α (TNFα) showed a significant increase in OMP-immunized fish. Challenged A. hydrophila for O. niloticus previously passively immunized with OMPs (A4, A5, A6, A8, and A11) in fish-raised sera showed a significant increase in RPS (20 to 100%) in the vaccinated groups. It is concluded that OMPs from Aeromonas spp. have been identified as suitable target for protection development, especially in the case of heterogenic bacteria. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the mineral content, and content of bioactive compounds in fruits of Cornelian cherry (Cornus mas L.). Neochlorogenic acid, chlorogenic acid, caffeic acid, and rutin were determined in the samples. Vitamin C content ranged from 610.36 to 1344 mg kg−1 FW. Content of K, Ca, P, Mg, and Na in samples ranged from 1750.8 to 2645.7 mg kg−1 FW, from 281.14 to 561.62 mg kg−1 FW, from 180.38 to 294.95 mg kg−1 FW, from 68.19 to 115.43 mg kg−1 FW, and from 2.48 to 71.33 mg kg−1 FW respectively. Content of Fe, Zn, Cu, Mn, Ni, Cr, and Co in samples ranged from 2.77 to 4.88 mg kg−1 FW, from 0.49 to 0.99 mg kg−1 FW, from 0.25 to 0.53 mg kg−1 FW, from 0.07 to 0.17 mg kg−1 FW, from 0.02 to 0.13 mg kg−1 FW, from 0.01 to 0.02 mg kg−1 FW, and from 0.01 to 0.08 mg kg−1 FW respectively. Variations across cultivars were found to be statistically significant, indicating that genetics is a key factor influencing the concentration of bioactive compounds and minerals in Cornelian cherry fruits. Understanding the genetic factors influencing mineral and bioactive compound content in cornelian cherry cultivars is essential for targeted breeding programs, crop improvement, and the development of cultivars with enhanced nutritional and health-promoting attributes. This knowledge contributes to sustainable agriculture and supports the production of crops that align with consumer preferences and health trends. [ABSTRACT FROM AUTHOR]

A number of synthesis parameters directly influence the degree of reticulation/geopolymerisation of metakaolin exposed to alkaline solutions of sodium hydroxide and/or sodium silicate. In the latter case, a sodium silicate solution can be depolymerised by the introduction of an appropriate amount of NaOH. The effects of the ageing of the activator solution on the reticulation of metakaolin-based geopolymers are quantified for the first time in this work. We studied the anionic species of the sodium silicate solution with the addition of NaOH made just before the preparation of the paste, 24 h or 7 days before. These three ageing periods cause a significant difference in the Si-bearing species in solution, as demonstrated by nuclear magnetic resonance on 29Si. The effect of these anionic species on the reticulation/polymerisation of metakaolin at room temperature was demonstrated by solid-state 27Al and 29Si MAS-NMR, the chemical stability in various solutions (deionised water, HCl, HNO3, H2SO4), and X-ray diffraction on geopolymer powders before and after immersion in acids. Compressive strength before and after the immersion in acidic media was an additional measurement to assess the overall structural stability of the 3D polymerised network of the final dense ceramic-like product. Ageing of the activator solution affected the chemical stability of the hardened geopolymers accompanied by a slight to severe reduction in strength after leaching in HNO3 or HCl and in H2SO4, respectively. The quantitative MAS-NMR description of the Si and Al coordination in the geopolymers was correlated with the chemical stability where the formulations with the higher number of Q4(0Al) and Q4(1Al) for the silicon species were more resistant (lower number of Na+ compensating for Al+3 to be exchanged with H+). The formulations with higher Al content in the structure, i.e. higher number of Q4(3Al) silicon species showed higher mechanical stability. These results show that the timing of the preparation of the alkaline activator is essential for a correct mix design. [ABSTRACT FROM AUTHOR]

Ventricular remodeling is one of the main causes of mortality from heart failure due to hypertension. Exploring its mechanism and finding therapeutic targets have become urgent scientific problems to be solved. A number of studies have shown that Mas, as an Ang-(1-7) specific receptor, was significantly reduced in myocardial tissue of rats undergoing hypertensive ventricular remodeling. It has been reported that Mas receptor levels are significantly downregulated in myocardium undergoing ventricular remodeling, but studies focused on intracellular and post-translational modifications of Mas are lacking. The results of this research are as follows: (1) PDZK1 interacts with the carboxyl terminus of Mas through its PDZ1 domain; (2) the expression of PDZK1 and Mas is decreased in rats undergoing hypertensive ventricular remodeling, and PDZK1 upregulation can ameliorate hypertensive myocardial fibrosis and myocardial hypertrophy; (3) PDZK1 enhances the stability of Mas protein through the proteasome pathway, and the proteasome inhibitor MG132 promotes hypertensive ventricular remodeling. PDZK1 improves ventricular remodeling in hypertensive rats by regulating Mas receptor stability. This study provides a scientific basis for the prevention and treatment of ventricular remodeling. [ABSTRACT FROM AUTHOR]

Sepsis-induced acute liver injury (ALI) is common in intensive care units. Angiotensin-converting enzyme 2 (ACE2) plays a vital role in hepatic fibrosis and steatosis; however, its role in sepsis-induced ALI remains unclear. This study found that hepatic ACE2 expression in cecal ligation and puncture (CLP)-treated mice significantly decreased 24 h after CLP. ACE2-transgenic (TG) mice exhibited a significant improvement in CLP-induced ALI, accompanied by the inhibition of hepatocyte apoptosis, oxidative stress, and inflammation, while ACE2-knockout mice demonstrated an opposite trend. During sepsis-induced ALI, ACE2-TG could also elevate the Ang-(1–7) and Mas receptor (MasR) levels in liver tissues. Interestingly, the MasR inhibitor A779 abrogated the favorable effects of ACE2 on CLP-induced ALI. In a bone marrow transplantation experiment, the ACE2-TG transplantation group showed significantly improved inflammation and liver dysfunction, less hepatocyte apoptosis, and reduced oxidative stress after CLP compared with the wild-type transplantation group. In contrast, the ACE2-knockout group showed poor inflammatory response and liver dysfunction, significantly more hepatocyte apoptosis, and elevated oxidative stress than the wild-type transplantation group after CLP. ACE2 protects against sepsis-induced ALI by inhibiting hepatocyte apoptosis, oxidative stress, and inflammation via the Ang-(1–7)–Mas receptor axis. Thus, targeting ACE2 may be a promising novel strategy for preventing and treating sepsis-induced ALI. [ABSTRACT FROM AUTHOR]

Silver-modified zeolites have demonstrated promising properties for hydrocarbon feedstock valorization and the oxidation of organic compounds. Within the frame of the scientific interest for selective oxidation of light alkenes on metal-modified zeolites, the transformation of propene on Ag/H-ZSM-5 zeolite in the presence of molecular oxygen has been monitored by 13C (CP) MAS NMR spectroscopy at 296–773 K. Silver-allyl intermediate species have been detected by 13C CP/MAS NMR, indicating that Ag+ sites are involved in propene transformation. It is assumed that oxygen and propene compete for the Ag+ adsorption sites, thus prompting propene adsorption on zeolite Brønsted acid sites (BAS) and its further transformation by oligomerization and conjunct polymerization. Among the products of propene oxidation by molecular oxygen, only carbon dioxide has been detected by 13C MAS NMR, implying high activity of Ag/H-ZSM-5 in alkene total oxidation. It is thus inferred that silver-modified zeolite is not a promising catalyst for propene selective oxidation to propene oxide and carbonyl group containing organics. [ABSTRACT FROM AUTHOR]

An Embedded multi-agent system (Embedded MAS) is an embedded cognitive system based on agents cooperating to control hardware devices. These agents are autonomous and proactive entities capable of decision-making and can constantly acquire new knowledge via interaction with other agents and the environment. Since the interaction between agents is relevant for acquiring new knowledge, issues such as the communicability and mobility of agents from different Embedded MAS must be highlighted. The classification of a MAS as Open or Closed only considers the mobility of agents, but communicability also needs to be considered. For this, we extend the notion of openness in these systems to consider the existence of Totally Closed and Limited Open MAS, to consider agents from an Embedded MAS without the ability to move or communicate or when they lose the ability to communicate but still can move to other systems. In cooperative missions where several devices adopt Embedded MAS, they should not become totally closed since they lose the ability to cooperate and could put the mission at risk. Some existent works considering Embedded MAS relies upon IoT infrastructures to guarantee communicability and mobility. But, in cases where these infrastructures are temporarily or permanently unavailable, the system becomes totally closed. Even when alternatives exist, they do not use cryptography. Therefore, we present a middleware for supporting the development of Embedded MAS, considering radiofrequency ad-hoc communication to reduce the dependency on centralized infrastructures. An extended protocol supports message exchange between devices using cryptography. We also present a proof of concept application and a formalization of our model. [ABSTRACT FROM AUTHOR]

Introduction: CT-based attenuation correction (CT-AC) plays a major role in accurate activity quantification by SPECT/CT imaging. However, the effect of kilovoltage peak (kVp) and quality-reference mAs (QRM) on the attenuation coefficient image (μ-map) and volume CT dose index (CTDIvol) have not yet been systematically evaluated. Therefore, the aim of this study was to fill this gap and investigate the influence of kVp and QRM on CT-AC in 177Lu SPECT/CT imaging. Methods: Seventy low-dose CT acquisitions of an Electron Density Phantom (seventeen inserts of nine tissue-equivalent materials) were acquired using various kVp and QRM combinations on a Siemens Symbia Intevo Bold SPECT/CT system. Using manufacturer reconstruction software, 177Lu μ-maps were generated for each CT image, and three low-dose CT related aspects were examined. First, the μ-map-based attenuation values (μmeasured) were compared with theoretical values (μtheoretical). Second, changes in 177Lu activity expected due to changes in the μ-map were calculated using a modified Chang method. Third, the noise in the μ-map was assessed by measuring the coefficient of variation in a volume of interest in the homogeneous section of the Electron Density Phantom. Lastly, two phantoms were designed to simulate attenuation in four tissue-equivalent materials for two different source geometries (1-mL and 10-mL syringes). 177Lu SPECT/CT imaging was performed using three different reconstruction algorithms (xSPECT Quant, Flash3D, STIR), and the SPECT-based activities were compared against the nominal activities in the sources. Results: The largest relative errors between μmeasured and μtheoretical were observed in the lung inhale insert (range: 18%-36%), while it remained below 6% for all other inserts. The resulting changes in 177Lu activity quantification were -3.5% in the lung inhale insert and less than -2.3% in all other inserts. Coefficient of variation and CTDIvol ranged from 0.3% and 3.6 mGy (130 kVp, 35 mAs) to 0.4% and 0.9 mGy (80 kVp, 20 mAs), respectively. The SPECT-based activity quantification using xSPECT Quant reconstructions outperformed all other reconstruction algorithms. Conclusion: This study shows that kVp and QRM values in low-dose CT imaging have a minimum effect on quantitative 177Lu SPECT/CT imaging, while the selection of low values of kVp and QRM reduce the CTDIvol. [ABSTRACT FROM AUTHOR]

Developing late-leafing genotypes is crucial for mitigating the impact of late-spring frosts in walnut cultivation. Marker-assisted selection (MAS) offers a rapid screening approach for walnut populations in breeding programs, addressing the long breeding cycle. This study aimed to validate Turkish molecular markers associated with leafing date in the Iranian walnut populations and to implement MAS to identify late-leafing genotypes. Two polymorphic SSR primers, 'JRHR209732' and 'CUJ-RBO12', were validated using 14 early- and late-leafing cultivars/genotypes. MAS was then implemented for a population of 91 Iranian walnuts from a breeding program. The results indicated the effective differentiation of the Iranian population using the markers from Turkey, suggesting genetic similarity between the walnut populations of the two countries. Furthermore, alleles with band sizes of 277 and 115 were associated with late-leafing, while band sizes of 289 and 92 indicated early-leafing. Phenological data over three consecutive years, along with SSR analysis, confirmed the validation and implementation of MAS. The SSR analysis identified 14 alleles across all accessions, with an average of 7 alleles per locus. High leafing time variation was observed in the studied population, and cluster analysis identified four major clusters, revealing similarities and dissimilarities among the accessions. Finally, genotypes 'Ch35T12', 'ChLa1', 'ChFr2', 'ChFr3', 'Ped35T1', 'Ped35T4', 'PedLa1', 'PedLa3', 'PedOp1', and 'ChPed2' were identified as late-leafing genotypes based on screening with late-leaf alleles. [ABSTRACT FROM AUTHOR]

The composition of anthocyanins of dogwood fruits was determined using reverse-phase HPLC with spectrophotometric and mass spectrometric detection. The procedure for determining the structure of individual components of extracts including 3-galactosides of delphinidine, cyanidine and pelargonidine and 3-robinobiosides (3-rhamnosylgalactosides) of cyanidine and pelargonidine is described. It was found that the content of delphinidin3-galactoside, as well as both 3-robinobiosides, may be insignificant when cyanidin and pelargonidin prevail in the composition of 3-galactosides. For the studied fruits, the level of anthocyanin accumulation can reach (depending on the intensity of coloring) 46 mg per 100 g of fresh fruits, while the concentration of anthocyanins in the peel of fruits is significantly higher – more than 390 mg per 100 g. When developing an exhaustive extraction of anthocyanins, a peculiarity of dogwood fruits was established, consisting in the fact that the extraction of anthocyanins with 0.1 M aqueous hydrochloric acid solution, unlike a large number of other natural sources studied, is practically impossible. The problem can be solved only by extraction with acidified water-alcohol mixtures with an ethanol content in the extractant of more than 30 vol.%, which indicates a high affinity of the components of the pulp of fruits to anthocyanins. [ABSTRACT FROM AUTHOR]

Objectives: Macrophage activation syndrome (MAS) is a severe complication of systemic juvenile idiopathic arthritis (SJIA). We aimed to compare the characteristics of SJIA patients who developed MAS in the disease course to those who never experienced MAS. Methods: Patients with SJIA were included. The features of the patients at the time of SJIA diagnosis were compared. Multivariate logistic regression and ROC analyses were used while evaluating factors associated with MAS. Results: Overall, 126 SJIA patients (M/F:1.17) were included. Eighty-six (68.2%) never had MAS. At the time of SJIA diagnosis, age was younger; the duration of fever was longer; rash, hepatomegaly, and splenomegaly were more frequent and arthralgia/arthritis was less common among patients who had MAS in the follow-up than those who never had MAS. Also, white blood cell, neutrophil, and platelet counts and fibrinogen were lower, while transaminases, lactate dehydrogenase, triglyceride (TG), and ferritin levels were higher among patients with MAS than those without MAS. The multivariate regression analysis disclosed age at symptom onset, duration of fever, platelet count, TG and ferritin levels as independent MAS predictors. For ferritin level/platelet count (F/P) ratio at the time of SJIA diagnosis, a threshold of ≥1.1 performed best to predict a MAS-prone disease course with a sensitivity of 90% and a specificity of 82.6%. Conclusion: The F/P ratio at the time of SJIA diagnosis may be a promising biomarker to predict MAS-prone disease course in SJIA. Determining MAS-prone patients at the time of SJIA diagnosis could assist physicians while tailoring SJIA treatment individually. Key points • Systemic juvenile idiopathic arthritis (SJIA) patients with macrophage activation syndrome (MAS) differ from SJIA patients who never have MAS, at the time of SJIA diagnosis. • It could be possible to predict a MAS-prone disease course at the time of SJIA diagnosis. • The ferritin/platelet ratio is a promising biomarker for predicting MAS-prone SJIA disease course. [ABSTRACT FROM AUTHOR]

Blinatumomab as a single agent has demonstrated superiority over salvage chemotherapy in patients with relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL), with manageable safety and efficacy. Though known to have anticipated drug toxicities including cytokine release syndrome (CRS) and neurotoxicity, there is only one prior report of macrophage activating syndrome (MAS) due to blinatumomab. Case Presentation: We report the first case of blinatumomab-induced MAS in an adult. The patient presented with fever, cough, and weakness on the second cycle of blinatumomab. Complete blood count was notable for severe leukopenia, with comprehensive metabolic panel notable for elevated alkaline phosphatase, AST, ALT, LDH, and hyperferritinemia consistent with MAS. The patient was already in MRD-negative remission at presentation with MAS. She responded rapidly to withholding the drug and administration of both tocilizumab and dexamethasone. She was able to restart therapy with blinatumomab dosed at 9 mcg/day with no recurrence of symptoms. Though MAS is not an expected association with blinatumomab, the risk for CRS is. Secondary MAS in this case likely shares a mechanism with other hyperinflammatory conditions. Management includes holding the offending agent, like blinatumomab, and administering tocilizumab and dexamethasone. Future research will be needed to predict which patients are at highest risk to develop MAS after similar T-cell therapies. [ABSTRACT FROM AUTHOR]

Patients with idiopathic pulmonary fibrosis show a strongly upregulated expression of chemokine CXCL14, whose target is still unknown. Screening of CXCL14 in a panel of human G protein-coupled receptors (GPCRs) revealed its potent and selective activation of the orphan MAS-related GPCR X2 (MRGPRX2). This receptor is expressed on mast cells and − like CXCL14 − upregulated in bronchial inflammation. CXCL14 induces robust activation of MRGPRX2 and its putative mouse ortholog MRGPRB2 in G protein-dependent and β-arrestin recruitment assays that is blocked by a selective MRGPRX2/B2 antagonist. Truncation combined with mutagenesis and computational studies identified the pharmacophoric sequence of CXCL14 and its presumed interaction with the receptor. Intriguingly, C-terminal domain sequences of CXCL14 consisting of 4 to 11 amino acids display similar or increased potency and efficacy compared to the full CXCL14 sequence (77 amino acids). These results provide a rational basis for the future development of potential idiopathic pulmonary fibrosis therapies. This study reveals that the proinflammatory chemokine CXCL14 activates MAS-related G protein-coupled receptor MRGPRX2; these results provide a rational basis for the future development of idiopathic pulmonary fibrosis therapies. [ABSTRACT FROM AUTHOR]

In recent years, solid-state 13C NMR spectroscopy using the techniques of cross-polarization (CP) and magic angle spinning (MAS) has been used to analyze plant materials, including wood. The composition, structure, and behavior of wood components determine the properties of wood materials in various conditions and are therefore important to know. In this work, differences in wood composition were studied for several tree species of central Russia (birch, aspen, spruce, and larch) by CP MAS 13C NMR spectroscopy. Peaks of CP MAS 13C NMR spectra were assigned to the main components of the wood. Cellulose was shown to occur in amorphous and crystalline forms; the presence of lignin was unambiguously confirmed by signals from aromatic carbon atoms; and hemicellulose was detected by signals from carbon atoms of the methyl groups of acetylxylose and L-rhamnose. Integral intensities were used to estimate the total proportion of cellulose and hemicellulose in relation to lignin. The lignin content in wood was observed to be maximal in the coniferous species (spruce and larch) and minimal in the deciduous species (aspen and birch). [ABSTRACT FROM AUTHOR]

While 1H-1H J-couplings are the cornerstone of all spectral assignment methods in solution-state NMR, they are yet to be observed in solids. Here we observe 1H-1H J-couplings in plastic crystals of (1S)-(−)-camphor in solid-state NMR at magic angle spinning (MAS) rates of 100 kHz and above. This is enabled in this special case because the intrinsic coherence lifetimes at fast MAS rates become longer than the inverse of the 1H-1H J couplings. For example, at 160 kHz MAS the coherence lifetimes are longer than 20 ms, corresponding to refocused linewidths of less than 15 Hz. As a result, we are able to record two-dimensional 1H-1H J resolved spectra that allow the observation and measurement of 1H-1H J-couplings in solid camphor. The J-couplings also lead to unambiguous through-bond correlations in 1H-1H refocused incredible natural abundance double quantum transfer (INADEQUATE) and uniform-sign cross-peak double-quantum-filtered correlation spectroscopy (UC2QFCOSY) experiments. The authors demonstrate the detection of 1H 1H J-couplings, which are difficult to observe in the solid state, in plastic crystals of camphor using solid state NMR at magic angle spinning rates of 100 kHz and above. [ABSTRACT FROM AUTHOR]

Associated water plays a significant role in the morphology of cellulose and the molecular interactions between polymer chains. It also affects the material properties and influences the interpretation of analysis results. In the present study the interaction of cellulose and water in well-defined cellulose samples, hydrogel beads prepared by regeneration of microcrystalline cellulose from organic electrolyte solution, are investigated by solid state 13C CP/MAS NMR. Drying of the hydrogel beads under ambient conditions gave condensed cellulose xerogel beads, which could be partly reswollen in water. The analysis of beads of different moisture content and under repeated drying and swelling afforded a better understanding of the hierarchical organization and crystallinity of cellulose II, which is broadly divisible into crystalline and surface residues in CP/MAS, and the nature of cellulose hornification. The changes in the 13C CP/MAS spectra of water- and D2O-swollen beads also provide new information on the role of immobilized bound water in intermolecular polarization transfer from water to cellulose during the cross-polarization pulse sequence, and evidence of the cellulose II reducing-end-group, which is more prominently observable in CP/MAS under dry conditions. [ABSTRACT FROM AUTHOR]

Backcross breeding is used to transfer an desirable trait from donor to recurrent parent (RP), and it takes six to seven generations for 99% recovery of the recurrent parent genome (RPG). Marker-assisted backcross breeding (MABB) was proposed to accelerate the recovery of the RPG. Over the period of time, MABB has evolved as per the available resources and time frame. One of the major modifications is the number of foreground-selected individuals which are subjected to background selection. This number varied widely and lacked consensus in different studies. Further, the major drawback of the existing method is that the DUS traits are recorded directly in the improved lines. Once the traits are fixed in the finished product, there is no going back to bring the corresponding traits of RP. The modified MABB method (DUS-MAS) can ensure higher recovery of DUS traits and RPG. A yield index has also been developed for the identification of high yielding individuals in backcross generation. In DUS-MAS, the foreground-positive individuals are selected first, and then individuals with a higher yield index are selected. Thereafter, the foreground and yield index positive individuals are selected for higher recovery of DUS traits. Five such individuals are subjected to marker-based background recovery of which only two with the highest recovery were advanced to the next generation. All these steps are to be followed in BC1F1, BC2F1, and BC2F2 generations. It substantially reduces the cost by reducing the use of laboratory chemicals by more than 75%. [ABSTRACT FROM AUTHOR]

Aluminum has been shown to significantly enhance the water incorporation capacity of orthoenstatite (OEn), but the incorporation mechanisms remained to be clarified. We performed a comprehensive one- and two-dimensional 1H, 29Si and 27Al NMR study on four hydrous aluminous OEn samples containing 1–8 wt% Al2O3 synthesized at 1.5 GPa and 900 °C to clarify the issue. The combined 1H MAS and static (non-spinning) NMR, 1H double-quantum and triple-quantum MAS NMR, and 27Al→1H CP MAS NMR and HETCOR results, in particular, unambiguously revealed that a large part of the incorporated water are present as proton pairs in Mg vacancies adjacent to Al, with one proton of each pair for the dominant proton pairs exhibiting significantly weaker hydrogen bonding than those in Al-free OEn. Proton pairs in Mg vacancies remote from Al are minor or absent for samples with 4–8 wt% Al2O3, and more abundant for a sample with 1 wt% Al2O3. Isolated protons due to coupled substitutions of Al + H for 1Si and 2Mg (both with weak hydrogen bonding) were also detected, but are less abundant than hitherto considered. The observed NMR peaks match well with those predicted for the corresponding OH defect models from our first-principles calculations. Thus, the enhancement of water solubility by Al for OEn are due to not only coupled substitutions of Al + H for 1Si and 2Mg, but also interactions of Al with proton pairs in Mg vacancies. These mechanisms may also be important in other nominally anhydrous aluminous silicate minerals. [ABSTRACT FROM AUTHOR]

Amyloid fibrils from Alzheimer's amyloid-beta peptides (Aβ) are found to be polymorphic. So far, 14 Aβ40 fibril structures have been determined. The mechanism of why one particular protein sequence adopts so many different three-dimensional structures is yet not understood. In this work, we describe the assignment of the NMR chemical shifts of two Alzheimer's disease fibril polymorphs, P1 and P2, which are formed by the amyloid-beta peptide Aβ40. The assignment is based on 13C-detected 3D NCACX and NCOCX experiments MAS solid-state NMR experiments. The fibril samples are prepared using an extensive seeding protocol in the absence and presence of the small heat shock protein αB-crystallin. In addition to manual assignments, we obtain chemical shift assignments using the automation software ARTINA. We present an analysis of the secondary chemical shifts and a discussion on the differences between the manual and automated assignment strategies. [ABSTRACT FROM AUTHOR]

To clarify the differences and similarities in the cytokine profiles of macrophage activating syndrome (MAS) between systemic lupus erythematosus (SLE) and adult-onset Still's disease (AOSD). The study participants included 9 patients with MAS-SLE, 22 with non-MAS-SLE, 9 with MAS-AOSD, and 13 with non-MAS-AOSD. Serum cytokine levels were measured using a multiplex bead assay. Cytokine levels were compared between patients with SLE and AOSD with/without MAS. Moreover, cytokine patterns were examined using principal component analysis (PCA) and cluster analysis. IL-6, IL-8, IL-18, and TNF-α levels were elevated in patients with SLE and AOSD. IFN-α levels were elevated in SLE, whereas IL-1β and IL-18 levels were elevated in AOSD. In SLE, IFN-α and IL-10 levels were higher in MAS than in non-MAS and controls. PCA revealed distinctive cytokine patterns in SLE and AOSD, SLE with IFN-α and IP-10, AOSD with IL-1β, IL-6, and IL-18, and enhanced cytokine production in MAS. PCA and cluster analysis showed no differences in cytokine patterns between the MAS and non-MAS groups. However, serum ferritin levels were correlated with IFN-α levels in SLE. Cytokine profiles differed between SLE and AOSD but not between MAS and non-MAS. MAS is induced by the enhancement of underlying cytokine abnormalities rather than by MAS-specific cytokine profiles. Type I IFN may be involved in MAS development in patients with SLE. [ABSTRACT FROM AUTHOR]

Phosphate-fluoride compounds MSbF(PO4)·H2O (M = Na, Rb, NH4) are studied by 19F, 31P, 1H NMR and by magic-angle spinning NMR (MAS NMR) in the temperature range 150-350 K. The types of ionic and molecular motions in these compounds are determined, their activation energies are estimated. The presence of acidic phosphate groups in sodium and rubidium compounds is established. The 19F MAS NMR spectra of antimony(III) phosphate fluorides are similar to each other due to the similar structure of these compounds, while the multitude of signals in the spectra indicates the disorder of cationic sublattices of the complexes. [ABSTRACT FROM AUTHOR]

Background: Rosacea is a chronic inflammatory disease characterized by persistent erythema, papules, and pustules, mainly on the skin of the face. Rosacea is difficult to treat; therefore, identifying new treatments is crucial. Mas-related G protein-coupled receptor X2 (MRGPRX2)-mediated mast cell (MC) activation is essential in the pathogenesis of rosacea. Casticin has been shown to exert anti-inflammatory effects; however, it remains unclear whether it can inhibit MRGPRX2 in treating rosacea. This study determined the therapeutic efficacy of casticin against rosacea by inhibiting MRGPRX2-mediated MC activation.A mouse model of LL37-induced rosacea-like dermatitis was employed. The pathological changes were evaluated using hematoxylin and eosin (H&E) staining, and MCs and CD4+ T cells were observed. Inflammatory mediators were analyzed using ELISA. Mouse skin lesions were collected for transcriptomic sequencing. We used an MRGPRX2-mediated MC degranulation model to evaluate the inhibitory effects of casticin in vitro. Molecular docking analysis, molecular dynamics simulations, and surface plasmon resonance evaluated the binding between casticin and MRGPRX2.Casticin attenuated the LL37-induced inflammatory phenotype and reactions in rosacea-like dermatitis. RNA-seq data showed that casticin inhibited MC activation in a mouse model of rosacea. Furthermore, casticin significantly reduced CD4 + T-cell infiltration. Moreover, casticin inhibited MC activation as an MRGPRX2 antagonist in vitro and in vivo by influencing the NF-κB signaling pathway.Our study demonstrated that casticin exhibits therapeutic efficacy against rosacea by inhibiting MC activation via MRGPRX2.Methods: Rosacea is a chronic inflammatory disease characterized by persistent erythema, papules, and pustules, mainly on the skin of the face. Rosacea is difficult to treat; therefore, identifying new treatments is crucial. Mas-related G protein-coupled receptor X2 (MRGPRX2)-mediated mast cell (MC) activation is essential in the pathogenesis of rosacea. Casticin has been shown to exert anti-inflammatory effects; however, it remains unclear whether it can inhibit MRGPRX2 in treating rosacea. This study determined the therapeutic efficacy of casticin against rosacea by inhibiting MRGPRX2-mediated MC activation.A mouse model of LL37-induced rosacea-like dermatitis was employed. The pathological changes were evaluated using hematoxylin and eosin (H&E) staining, and MCs and CD4+ T cells were observed. Inflammatory mediators were analyzed using ELISA. Mouse skin lesions were collected for transcriptomic sequencing. We used an MRGPRX2-mediated MC degranulation model to evaluate the inhibitory effects of casticin in vitro. Molecular docking analysis, molecular dynamics simulations, and surface plasmon resonance evaluated the binding between casticin and MRGPRX2.Casticin attenuated the LL37-induced inflammatory phenotype and reactions in rosacea-like dermatitis. RNA-seq data showed that casticin inhibited MC activation in a mouse model of rosacea. Furthermore, casticin significantly reduced CD4 + T-cell infiltration. Moreover, casticin inhibited MC activation as an MRGPRX2 antagonist in vitro and in vivo by influencing the NF-κB signaling pathway.Our study demonstrated that casticin exhibits therapeutic efficacy against rosacea by inhibiting MC activation via MRGPRX2.Results: Rosacea is a chronic inflammatory disease characterized by persistent erythema, papules, and pustules, mainly on the skin of the face. Rosacea is difficult to treat; therefore, identifying new treatments is crucial. Mas-related G protein-coupled receptor X2 (MRGPRX2)-mediated mast cell (MC) activation is essential in the pathogenesis of rosacea. Casticin has been shown to exert anti-inflammatory effects; however, it remains unclear whether it can inhibit MRGPRX2 in treating rosacea. This study determined the therapeutic efficacy of casticin against rosacea by inhibiting MRGPRX2-mediated MC activation.A mouse model of LL37-induced rosacea-like dermatitis was employed. The pathological changes were evaluated using hematoxylin and eosin (H&E) staining, and MCs and CD4+ T cells were observed. Inflammatory mediators were analyzed using ELISA. Mouse skin lesions were collected for transcriptomic sequencing. We used an MRGPRX2-mediated MC degranulation model to evaluate the inhibitory effects of casticin in vitro. Molecular docking analysis, molecular dynamics simulations, and surface plasmon resonance evaluated the binding between casticin and MRGPRX2.Casticin attenuated the LL37-induced inflammatory phenotype and reactions in rosacea-like dermatitis. RNA-seq data showed that casticin inhibited MC activation in a mouse model of rosacea. Furthermore, casticin significantly reduced CD4 + T-cell infiltration. Moreover, casticin inhibited MC activation as an MRGPRX2 antagonist in vitro and in vivo by influencing the NF-κB signaling pathway.Our study demonstrated that casticin exhibits therapeutic efficacy against rosacea by inhibiting MC activation via MRGPRX2.Conclusion: Rosacea is a chronic inflammatory disease characterized by persistent erythema, papules, and pustules, mainly on the skin of the face. Rosacea is difficult to treat; therefore, identifying new treatments is crucial. Mas-related G protein-coupled receptor X2 (MRGPRX2)-mediated mast cell (MC) activation is essential in the pathogenesis of rosacea. Casticin has been shown to exert anti-inflammatory effects; however, it remains unclear whether it can inhibit MRGPRX2 in treating rosacea. This study determined the therapeutic efficacy of casticin against rosacea by inhibiting MRGPRX2-mediated MC activation.A mouse model of LL37-induced rosacea-like dermatitis was employed. The pathological changes were evaluated using hematoxylin and eosin (H&E) staining, and MCs and CD4+ T cells were observed. Inflammatory mediators were analyzed using ELISA. Mouse skin lesions were collected for transcriptomic sequencing. We used an MRGPRX2-mediated MC degranulation model to evaluate the inhibitory effects of casticin in vitro. Molecular docking analysis, molecular dynamics simulations, and surface plasmon resonance evaluated the binding between casticin and MRGPRX2.Casticin attenuated the LL37-induced inflammatory phenotype and reactions in rosacea-like dermatitis. RNA-seq data showed that casticin inhibited MC activation in a mouse model of rosacea. Furthermore, casticin significantly reduced CD4 + T-cell infiltration. Moreover, casticin inhibited MC activation as an MRGPRX2 antagonist in vitro and in vivo by influencing the NF-κB signaling pathway.Our study demonstrated that casticin exhibits therapeutic efficacy against rosacea by inhibiting MC activation via MRGPRX2. [ABSTRACT FROM AUTHOR]

Studying the surface chemistry of functionalized cellulose nanofibrils at atomic scale is an ongoing challenge, mainly because FT-IR, NMR, XPS and RAMAN spectroscopy are limited in sensitivity or resolution. Herein, we show that dynamic nuclear polarization (DNP) enhanced 13 C and 15 N solid-state NMR is a uniquely suited technique to optimize the drug loading on nanocellulose using aqueous heterogenous chemistry. We compare the efficiency of two conventional coupling agents (DMTMM vs EDC/NHS) to bind a complex prodrug of ciprofloxacin designed for controlled drug release. Besides quantifying the drug grafting, we also evidence the challenge to control the concurrent prodrug adsorption and to optimize washing procedures. We notably highlight the presence of an unexpected prodrug cleavage mechanism triggered by carboxylates at the surface of the cellulose nanofibrils., (© 2023. The Author(s).)

Solution NMR is typically applied to biological systems with molecular weights < 40 kDa whereas magic-angle-spinning (MAS) solid-state NMR traditionally targets very large, oligomeric proteins and complexes exceeding 500 kDa in mass, including fibrils and crystalline protein preparations. Here, we propose that the gap between these size regimes can be filled by the approach presented that enables investigation of large, soluble and fully protonated proteins in the range of 40–140 kDa. As a key step, ultracentrifugation produces a highly concentrated, gel-like state, resembling a dense phase in spontaneous liquid-liquid phase separation (LLPS). By means of three examples, a Sulfolobus acidocaldarius bifurcating electron transfer flavoprotein (SaETF), tryptophan synthases from Salmonella typhimurium (StTS) and their dimeric β-subunits from Pyrococcus furiosus (PfTrpB), we show that such samples yield well-resolved proton-detected 2D and 3D NMR spectra at 100 kHz MAS without heterogeneous broadening, similar to diluted liquids. Herein, we provide practical guidance on centrifugation conditions and tools, sample behavior, and line widths expected. We demonstrate that the observed chemical shifts correspond to those obtained from µM/low mM solutions or crystalline samples, indicating structural integrity. Nitrogen line widths as low as 20–30 Hz are observed. The presented approach is advantageous for proteins or nucleic acids that cannot be deuterated due to the expression system used, or where relevant protons cannot be re-incorporated after expression in deuterated medium, and it circumvents crystallization. Importantly, it allows the use of low-glycerol buffers in dynamic nuclear polarization (DNP) NMR of proteins as demonstrated with the cyanobacterial phytochrome Cph1. [ABSTRACT FROM AUTHOR]

Based on quantum-chemical computation, a solution with periodic boundary conditions (PBC) was employed within density functional theory (DFT) simulations in order to assign the chemical shifts in the 27Al MAS NMR spectra of Al-BEA (HBEA) zeolite (Si/Al = 31) to the individual crystallographic T-sites calculated for polymorph B of an identical zeolite. The results were compared both to relevant published reports (Si/Al = 71 and 75) and to the experimental data previously obtained by the authors for a mixture of polymorphs (Si/Al = 25). Deconvolution of the 27Al MAS NMR spectrum into Al signals at different T-sites of polymorph B was compared to a similar deconvolution for polymorph A. [ABSTRACT FROM AUTHOR]

To characterize clinical and laboratory signs of patients with Still's disease experiencing macrophage activation syndrome (MAS) and identify factors associated with MAS development. Patients with Still's disease classified according to internationally accepted criteria were enrolled in the AutoInflammatory Disease Alliance (AIDA) Still's Disease Registry. Clinical and laboratory features observed during the inflammatory attack complicated by MAS were included in univariate and multivariate logistic regression analysis to identify factors associated to MAS development. A total of 414 patients with Still's disease were included; 39 (9.4%) of them developed MAS during clinical history. At univariate analyses, the following variables were significantly associated with MAS: classification of arthritis based on the number of joints involved (p = 0.003), liver involvement (p = 0.04), hepatomegaly (p = 0.02), hepatic failure (p = 0.01), axillary lymphadenopathy (p = 0.04), pneumonia (p = 0.03), acute respiratory distress syndrome (p < 0.001), platelet abnormalities (p < 0.001), high serum ferritin levels (p = 0.009), abnormal liver function tests (p = 0.009), hypoalbuminemia (p = 0.002), increased LDH (p = 0.001), and LDH serum levels (p < 0.001). At multivariate analysis, hepatomegaly (OR 8.7, 95% CI 1.9–52.6, p = 0.007) and monoarthritis (OR 15.8, 95% CI 2.9–97.1, p = 0.001), were directly associated with MAS, while the decade of life at Still's disease onset (OR 0.6, 95% CI 0.4–0.9, p = 0.045), a normal platelet count (OR 0.1, 95% CI 0.01–0.8, p = 0.034) or thrombocytosis (OR 0.01, 95% CI 0.0–0.2, p = 0.008) resulted to be protective. Clinical and laboratory factors associated with MAS development have been identified in a large cohort of patients based on real-life data. [ABSTRACT FROM AUTHOR]

The management of nuclear wastes has long been a problem that hinders the sustainable and clean utilization of nuclear energy since the advent of nuclear power. These nuclear wastes include minor actinides (MAs: 237Np, 241Am, 243Am, 244Cm and 245Cm) and long-lived fission products (LLFPs: 79Se, 93Zr, 99Tc, 107Pd, 129I and 135Cs), and yet are hard to be handled. In this work, we propose a scheme that can transmute almost all the MAs and LLFPs with a lead-cooled fast reactor (LFR). In this scheme, the MAs and the LLFPs are loaded to the fuel assembly and the blanket assembly for transmutation, respectively. In order to study the effect of MAs loading on the operation of the core, the neutron flux distribution, spectra, and the keff are further compared with and without MAs loading. Then the LLFPs composition is optimized and the support ratio is obtained to be 1.22 for 237Np, 1.63 for 241Am, 1.27 for 243Am, 1.32 for 79Se, 1.53 for 99Tc, 1.02 for 107Pd, and 1.12 for 129I, respectively, indicating that a self-sustained transmutation can be achieved. Accordingly, the transmutation rate of these nuclides was 13.07%/y for 237Np, 15.18%/y for 241Am, 13.34%/y for 243Am, 0.58%/y for 79Se, 0.92%/y for 99Tc, 1.17%/y for 107Pd, 0.56%/y for 129I. Our results show that a lead-cooled fast reactor can be potentially used to manage nuclear wastes with high levels of long-lived radioactivity. [ABSTRACT FROM AUTHOR]

Bioactive compounds of cornelian cherry (Cornus mas L.) fruits were extracted by green extraction methods including ultrasound-assisted (with three solvents: water, water/ethanol 50:50 v/v, and ethanol), supercritical fluid, and subcritical water extraction. Evaluation of the flavonoid and tocopherol compounds, β-carotene/linoleic acid test, and oil oxidative stability index assay were used to quantify the antioxidant power of cornelian cherry extracts. In β-carotene/linoleic acid test, a strong antioxidant activity of 85.84% was observed in the water/ethanol (50:50, v/v) ultrasound assisted extract, which also had the highest extraction yield and total flavonoid and tocopherol contents achieved by this method. In oil oxidative stability index assay, cornelian cherry extracts had higher resistance to oxidation than the tert-butylhydroquinone (TBHQ) synthetic antioxidant. Among the extracts, the longest induction time of 4.50 h belonged to water/ethanol (50:50, v/v) ultrasound-assisted extract. High and significant correlation was found between the extracted components and antioxidant capacity. This research demonstrated that the cornelian cherry fruit can be used as a potential source of natural antioxidant in food industry. [ABSTRACT FROM AUTHOR]

Chemisorption binding of gold(III) by mercury(II) N,N-diisobutyldithiocarbamate from a solution of H[AuCl4] in 2 M HCl is accompanied by a complete redistribution of ligands between the coordination spheres of metals, which leads to the formation of the [Au(S2CNBui2)2]2[Hg2Cl6] compound belonging to double complex salts. According to X-ray diffraction data, the mutual binding of ionic structural units due to non-valent secondary (Au···S and S···Cl) interactions promotes the formation of a supramolecular 2D pseudopolymer structure of the complex. Thermolysis of this complex was studied by the simultaneous thermal analysis method. [ABSTRACT FROM AUTHOR]

Photovoltaic (PV) resources' installation has numerous advantages in distribution feeders nonetheless they may threaten the selectivity and reliability of protective installations. All proposed schemes including employing distance or directional overcurrent relays, mathematics methods, online overcurrent relay settings change, fault current limiters, PV disconnection after fault, computing optimal installation location of PVs, and the others are too costly or complex or inefficient in PV-penetrated feeders. This paper proposes a new central processor unit to create a smart overcurrent relay and prohibit protection blinding, nuisance tripping, unwanted tripping, and synchronous tripping of overcurrent relay in a PV-penetrated distribution feeder. Firstly, the processor consists of four layers of the multi-agent system, which receives information on the relays and sensed current via the grid. Secondly, each agent is responsible to prevent a separate maloperation event and scrutinizing the input information. Finally, it directs the manipulated commend to the respective breaker if relay has acted incorrectly. Overcurrent relays become smart and miscoordination and maloperation problems are corrected completely by implementing the proposed processor. The proposed scheme is fast, offline, inexpensive, independent of the fault and PV installation location, type and impedance of the fault, and PV capacity. The results indicate the proposed plan has acted successfully with 100% efficiency in all scenarios. [ABSTRACT FROM AUTHOR]

This research characterizes key metabolites in the leaf from Citronella gongonha Martius (Mart.) Howard (Cardiopteridaceae). All metabolites were assessed in intact leaf tissue by proton (1H) high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy integrated with the principal component analysis (PCA) to depict molecular association with the seasonal change. The major 'known unknown' metabolites detected in 1H HR-MAS NMR were derivatives of flavonoid, polyphenolic and monoterpenoid compounds such as kaempferol-3-O-dihexoside, caffeoyl glucoside (2), 3-O-caffeoylquinic acid (3), 5-O-caffeoylquinic acid (4), kingiside (5), 8-epi-kingisidic acid (6), (7α)-7-O-methylmorroniside (7), (7β)-7-O-methylmorroniside (8) and alpigenoside (9) together with the universally occurring sucrose (10), α-glucoses (11, 12), alanine (13), and fatty (linolenic) acid (14). Several of the major metabolites (1, 2–9) were additionally confirmed by liquid chromatography tandem mass spectrometry (LC–MS/MS). In regard with the PCA results, metabolites 1, 2–9 and 14 were influenced by seasonal variation and/or from further (a) biotic environmental conditions. The findings in this work indicate that C. gongonha Mart. is an effective medicinal plant by preserving particularly compounds 2, 3–9 in abundant amounts. Because of close susceptibility with seasonal shift and ecological trends, further longitudinal studies are needed to realize the physiology and mechanism involved in the production of these and new metabolites in this plant under controlled conditions. Also, future studies are recommended to classify different epimers, especially of the phenolics and monoterpenoids in the given plant. [ABSTRACT FROM AUTHOR]

We study whether deep neural network based algorithm can filter out mammography phantom images that will pass or fail. With 543 phantom images generated from a mammography unit, we created VGG16 based phantom shape scoring models (multi-and binary-class classifiers). Using these models we designed filtering algorithms that can filter failed or passed phantom images. 61 phantom images obtained from two different medical institutions were used for external validation. The performances of the scoring models show an F1-score of 0.69 (95% confidence interval (CI) 0.65, 0.72) for multi-class classifiers and an F1-score of 0.93 (95% CI 0.92, 0.95) and area under the receiver operating characteristic curve of 0.97 (95% CI 0.96, 0.98) for binary-class classifiers. A total of 42 of the 61 phantom images (69%) were filtered by the filtering algorithms without further need for assessment from a human observer. This study demonstrated the potential to reduce the human workload from mammographic phantom interpretation using the deep neural network based algorithm. [ABSTRACT FROM AUTHOR]

Determination of protein structure and dynamics is key to understand the mechanism of protein action. Perdeuterated proteins have been used to obtain high resolution/sensitivty NMR experiments via proton-detection. These methods utilizes 1H, 13C and 15N nuclei for chemical shift dispersion or relaxation probes, despite the existing abundant deuterons. However, a high-sensitivity NMR method to utilize deuterons and e.g. determine site-specific deuterium quadrupolar pattern information has been lacking due to technical difficulties associated with deuterium's large quadrupolar couplings. Here, we present a novel deuterium-excited and proton-detected three-dimensional 2H–13C–1H MAS NMR experiment to utilize deuterons and to obtain site-specific methyl 2H quadrupolar patterns on detuterated proteins for the first time. A high-resolution fingerprint 1H–15N HSQC-spectrum is correlated with the anisotropic deuterium quadrupolar tensor in the third dimension. Results from a model perdeuterated protein has been shown. [ABSTRACT FROM AUTHOR]

This paper formally introduces Hart–Mas-Colell consistency for general (possibly multi-valued) solutions for cooperative games with transferable utility. This notion is used to axiomatically characterize the core on the domain of convex games. Moreover, we characterize all nonempty solutions satisfying individual rationality, anonymity, scale covariance, superadditivity, weak Hart–Mas-Colell consistency, and converse Hart–Mas-Colell consistency. This family consists of (a) the Shapley value, (b) all homothetic images of the core with the Shapley value as center of homothety and with positive ratios of homothety not larger than one, and (c) their relative interiors. [ABSTRACT FROM AUTHOR]

Optimal control (OCl) can be traced back to the 1960s when it was utilised for solving an optimisation problem (OP). In the OCl technique, a stable controller can be obtained by optimising a cost function (CF). This means that the performance provided by an OCl technique is the best in any instance. Nevertheless, this performance is not unique. Additionally, the parameters are not optimal. As such, there is a need to improve the technique so that the performance and the parameters are optimal. It has many applications in different fields of study such as engineering. There exist different OCl techniques such as Linear Quadratic Gaussian (LQG), Model Predictive Control (MPCl), Kalman Filter (KF), Linear Quadratic Regulator (LQR), etc. LQR and LQG are among the OCl techniques that are becoming popular in the industry and the research community. These controllers can provide robust stability because of their outstanding properties. Robustness to modelling uncertainty and noise (particular to LQG), closed-loop stability, direct input control, optimal input control, etc., are some of the properties that lead to this robust stability provided by these controllers. Nevertheless, one of their major problems is the tuning method. Conventionally, these controllers are tuned using classical methods such as Bryson's, analytical, trial-and-error, etc., methods. But these methods are associated with a lot of issues, such as time consumption, requiring experience and understanding of the problem at hand, lack of guaranteeing optimal values, etc., which lead to performance, stability, robustness, etc., problems. To solve these issues, researchers tend to use computational (optimisation) methods which proved to be more efficient. Consequently, a comprehensive state-of-the-art review of the recent studies that used computational methods for the improvement of OCl is presented in this paper. Different MAs that have been used to implement optimised LQR and LQG controls have been presented where the most used MAs are discussed in detail. The extent to which these MAs improved the control techniques is critically analysed. Additionally, optimised hybrids of these control techniques have been considered. Furthermore, the most controlled systems are discussed in detail including system modelling and state space representation derivation. The implementation modes of the techniques have been analysed. Some future research directions are also outlined. In essence, the work's major goal is to provide a comprehensive guide for researchers on computational methods usage for OCl improvement using LQR and LQG as case studies. [ABSTRACT FROM AUTHOR]

Purpose of Review: Clinical interest in non-IgE activation of mast cells has been growing since the description of the human MRGPRX2 receptor. Its participation in many allergic and inflammatory conditions such as non histaminergic itch, urticaria, asthma and drug hypersensitivity has been growing. We present here an updated review of its structure, expression and biology to help understand conditions and diseases attributed to its activation and/or overpexression and the search for agonists and antagonists of clinical utility. Recent Findings: The description of patients presenting anaphylaxis when exposed to one or multiple MRGPRX2 agonists such as general anesthetics, antibiotics, opiods and other agents has provided evidence of potential heterogeneity in humans. Summary: This review provides the most recent developments into the receptor structure, tissue expression and signaling pathways including the potential enhancement of IgE-mediated mast cell activation. New insight into its agonists and antagonists is described and future developments to adress its modulations. [ABSTRACT FROM AUTHOR]

The α-synuclein (α-syn) amyloid fibrils are involved in various neurogenerative diseases. Solid-state NMR (ssNMR) has been showed as a powerful tool to study α-syn aggregates. Here, we report the 1H, 13C and 15N back-bone chemical shifts of a new α-syn polymorph obtained using proton-detected ssNMR spectroscopy under fast (95 kHz) magic-angle spinning conditions. The manual chemical shift assignments were cross-validated using FLYA algorithm. The secondary structural elements of α-syn fibrils were calculated using 13C chemical shift differences and TALOS software. [ABSTRACT FROM AUTHOR]

Chronic granulomatous disease (CGD) is a rare inborn error of immunity (IEI), characterized by a deficient phagocyte killing due to the inability of NADPH oxidase to produce reactive oxygen species in the phagosome. Patients with CGD suffer from severe and recurrent infections and chronic inflammatory disorders. Onset of CGD has been rarely reported in neonates and only as single case reports or small case series. We report here the cases of three newborns from two different kindreds, presenting with novel infectious and inflammatory phenotypes associated with CGD. A girl with CYBA deficiency presented with necrotizing pneumonia, requiring a prolonged antibiotic treatment and resulting in fibrotic pulmonary changes. From the second kindred, the first of two brothers developed a fatal Burkholderia multivorans sepsis and died at 24 days of life. His younger brother had a diagnosis of CYBB deficiency and presented with Macrophage Activation Syndrome/Hemophagocytic Lympho-Histiocytosis (MAS/HLH) without any infection, that could be controlled with steroids. We further report the findings of a review of the literature and show that the spectrum of microorganisms causing infections in neonates with CGD is similar to that of older patients, but the clinical manifestations are more diverse, especially those related to the inflammatory syndromes. Our findings extend the spectrum of the clinical presentation of CGD to include unusual neonatal phenotypes. The recognition of the very early, potentially life-threatening manifestations of CGD is crucial for a prompt diagnosis, improvement of survival and reduction of the risk of long-term sequelae. [ABSTRACT FROM AUTHOR]

In the last two decades, an exponentially growing number of meta-analyses (MAs) synthesize thousands of peer-reviewed studies on the environmental impacts of farming practices (FPs). This paper describes the iMAP-FP evidence library, a comprehensive dataset on the effects of 34 categories of FPs (such as agronomic practices, cropping and livestock systems, land management options and mitigation techniques) on 34 impacts including climate mitigation, soil health, environmental pollution, water use, nutrients cycling, biodiversity, and agricultural productivity. Through systematic screening, 570 MAs published since 2000 were selected and categorized according to the type of FP. We assessed their impacts, the geographic regions covered, and their quality. We extracted 3,811 effects and their statistical significance associated with sustainable FPs (intervention) compared to a control (typically conventional agriculture) across 223 different intervention-control pairs. Our dataset is accompanied with an online free-access library, which includes a catalogue of synthetic reports summarizing the available evidence on each evaluated FP. [ABSTRACT FROM AUTHOR]

Background: A number of Italian grape berry varieties, such as Fiano (F) and Pallagrello Nero (P), represent National strategic products. Therefore, it is important to identify soil conditions emphasizing their peculiar characteristics as well as find innovative and sustainable treatments improving their compositional and nutraceutical quality. The field spray preparation 500 is a biodynamic product that is presumed to serve as biostimulant on the vine. However, so far, the scientific results probing its effectiveness are still lacking. Moreover, it is necessary to establish a reliable relationship between the grape quality and the spatial microvariability of the vineyard's soil. On this basis, the main objective of this work consisted in correlating structural and morphological characteristics (via MRI), the primary metabolome (via semi-solid state HRMAS NMR) and important nutraceutical parameters (total phenols and antioxidants via DPPH assay) of F and P grapes with both the action of preparation 500 biostimulant and the vineyard soil microvariability, based on soil apparent electrical conductivity. Results: HRMAS enabled the identification of the primary metabolome of F and P. The elaboration of 1H NMR spectra through chemometrics revealed significant changes in F and P grapes, accounting for both soil microvariability and the application of field spray (the latter also confirmed by PLS-DA and Heat-map clustering). Interestingly, for both F and P it was observed a significantly lower content of carbohydrates after biostimulant treatment while MRI revealed diagnostic structural and internal details of intact grapes. The combined use of proton parametric indices, such as relaxation times and diffusion coefficients, indicated alterations induced in grapes by both the spatial microvariability of the soil and the effects of investigated biostimulant. Interestingly, a tight correlation was found between MRI transverse relaxation time and the contents in total phenols and antioxidants. Conclusions: Our results have proven that both soil spatial microvariability and the application of field spray preparation 500 significantly affect the structural, metabolomic and nutraceutical characteristics of grapes. Moreover, the preparation 500 treatment has increased the nutraceutical value of grapes. Importantly, these data may be potentially used to promote and protect biodynamic grape and predict the quality of the resulting wines. [ABSTRACT FROM AUTHOR]

Crystalline bismuth(III) dithiocarbamato-chlorido complexes [Bi{S2CN(C3H7)2}Cl2] (I) and [Bi{S2CN(iso-C4H9)2}2Cl] (II) were prepared and comparatively studied by (13C, 15N) CP-MAS NMR spectroscopy, IR spectroscopy, and X-ray diffraction (CIF files CCDC nos. 1971976 and 1971975, respectively). The dithiocarbamate ligands are typically coordinated in the S,S'-iso- (I) or aniso- (II) bidentate-terminal mode. In each of the compounds, neighboring molecules are connected through one or two μ2-Cl– ligands into zigzag-like polymer chains, in which the central atom has sixfold coordination: [BiS2Cl4] (I) or [BiS4Cl2] (II). The binding unit in the polymer chains of I is a four-membered [Bi–(μ-Cl)2–Bi] metallocycle in the butterfly conformation (the dihedral angle is 140.51(3)°). Therefore, stronger binding of heteroleptic molecules in polymer chains leads to a considerably shorter interatomic Bi–Bi distances in I (4.0904(4) Å) than in II (4.8772(4) Å). The thermal behavior of heteroleptic bismuth(III) complexes was studied by simultaneous thermal analysis with recording of TG and DSC curves. Although the major product of thermal transformations of I and II is Bi2S3, the microprobe method also identified the presence of reduced bismuth and BiCl3. [ABSTRACT FROM AUTHOR]

The interaction of zinc(II) di-iso-butyldithiocarbamate with [AuCl4]— anions in 2M HCl is studied. The result of chemisorption binding of gold(III) from a solution to the solid phase is the formation of double ionic complexes of the compositions [Au{S2CN(iso-C4H9)2}2]2[Zn2Cl6] (1) and [Au{S2CN(iso-C4H9)2}2][Zn{S2CN(iso-C4H9)2}Cl2] (2). The chemical identification of preparatively isolated crystalline compounds was performed by 13C CP-MAS NMR spectroscopy. According to single crystal X-ray diffraction data, structural units of complex 1 are a binuclear zinc anion and non-equivalent complex [Au{S2CN(iso-C4H9)2}2]+ cations: centrosymmetric A with the Au(1) atom and С – Au(3) and non-centrosymmetric В – Au(2). With the participation of secondary Cl⋯S bonds (3.2407 Å and 3.2756 Å), В cations and anions form supramolecular ionic pairs. The structure of 2 in turn involves the centrosymmetric gold(III) cation whose counterion is a mixed-ligand dithiocarbamato-chlorido anion of zinc(II). Pairs of non-equivalent secondary Cl⋯S bonds (3.2337 Å and 3.3151 Å) combine the ionic structural units of 2 into zigzag-like pseudo-polymeric chains along which the alternation of complex cations and anions is noted. Thermolysis of complexes in cationic and anionic parts is accompanied by the quantitative regeneration of bound gold along with the formation of ZnCl2 and ZnS. [ABSTRACT FROM AUTHOR]

Malignant transformation of fibrous dysplasia lesions has been reported in patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS). Recently, we have observed an increased risk for breast cancer. In this study, the prevalence of skeletal and extraskeletal malignancies in patients with FD/MAS in the Netherlands was assessed by analyzing data from our cohort of FD/MAS patients, the Dutch Pathology Registry (PALGA), and the Netherlands Cancer Registry (NCR). We extracted data on sex, age at diagnosis of FD/MAS, type of FD/MAS, type of malignancy, and age at diagnosis of malignancy and histology of bone and malignant tissue when available, including GNAS-mutation analysis from patients' medical records. Standardized Morbidity Ratios (SMRs) with 95% confidence intervals were calculated. Twelve malignancies were identified in the LUMC FD/MAS cohort and 100 in the PALGA cohort. In this cohort, SMR was increased for osteosarcoma (19.7, 95% CI 3.5-48.9), cervical cancer (4.93, 95%CI 1.7-8.2), thyroid cancer (3.71, 95% CI 1.1-7.8), prostate cancer (3.08, 95% CI 1.8-4.6), and melanoma (2.01, 95%CI 1.2-3.1). SMRs for pancreatic cancer or hepatocellular carcinoma could not be calculated due to low numbers. The small number of malignancies identified in our FD/MAS cohort precluded the calculation of SMRs for our cohort specifically. Our findings show that patients with FD/MAS appear to have an increased risk for osteosarcoma, cervical, thyroid, and prostate cancer and melanoma. However, these data should be interpreted with caution, as true incidence rates of the identified malignancies may be influenced by the inclusion of only patients with histologically confirmed FD/MAS. The etiology of this increased risk for malignancies still needs to be elucidated. [ABSTRACT FROM AUTHOR]

Introduction: Patients with adult-onset Still's disease (AOSD) are at risk of developing macrophage activation syndrome (MAS), a life-threatening condition. Some cases of MAS have been reported following the use of biological agents, highlighting the need to identify contributing factors. This study aims to examine the characteristics of MAS in patients with AOSD treated with anakinra (ANA) or tocilizumab (TCZ). Methods: A systematic search was conducted across four online databases to identify studies reporting the incidence rates of MAS in patients with AOSD treated with ANA or TCZ. Meta-analysis was performed using a random-effects model and the generic inverse variance method to estimate the pooled incidence rates. The difference in incidence rates of MAS between TCZ and ANA was assessed. Additionally, we analyzed laboratory data and clinical features of AOSD cases at our institution, stratifying them into two groups: those who developed MAS after TCZ administration and those who did not. Results: Of the 455 screened articles, we included five ANA and six TCZ studies. The pooled incidence rates of MAS were 1.50% (95% confidence interval [CI], 0–3.36) for ANA (345 patients) and 14.01% (95% CI 4.51–23.51) for TCZ (94 patients). MAS incidence was significantly higher in the TCZ group (P = 0.01). Among the 17 patients from our institution, the six patients who developed MAS had significantly higher white blood cell and neutrophil counts, as well as elevated levels of lactate dehydrogenase, C-reactive protein, and ferritin before TCZ induction (P < 0.05). Conclusions: In patients with AOSD, the manifestation of MAS is influenced by multiple causative factors. Consequently, the administration of TCZ should be approached with caution, particularly in patients exhibiting elevated inflammatory markers. Trial Registration: This study was registered with the Clinical Trial Registry of the University Hospital Medical Information Network (Japan) as UMIN000049243. [ABSTRACT FROM AUTHOR]

The long-term issues of nuclear power systems are the effective use of uranium resources and the reduction of radioactive waste. Important radioactive wastes are minor actinides (MAs: 237Np, 241Am, 243Am, etc.) and long-lived fission products (LLFPs: 129I, 99Tc, 79Se, etc.). The purpose of this study was to show a concept that can simultaneously achieve the breeding of fissile materials and the transmutation of MAs and LLFPs in one fast reactor. Transmutation was carried out by loading innovative Duplex-type MA fuel in the core region and LLFP-containing moderator in the first layer of the radial blanket. Breeding was achieved in the core and axial blanket. As a result, it was clarified that in this fast breeder reactor, a breeding ratio of approximately 1.1 was obtained, and MAs and LLFPs achieved a support ratio of 1 or more. The transmutation rate was 10.3%/y for 237Np, 14.1%/y for 241Am, 9.9%/y for 243Am, 1.6%/y for 129I, 0.75%/y for 99Tc, and 4%/y for 79Se. By simultaneously breeding fissile materials and transmuting MAs and LLFPs in one fast reactor, it will be possible to solve the long-term issues of the nuclear power reactor system, such as securing nuclear fuel resources and reducing radioactive waste. [ABSTRACT FROM AUTHOR]

In the last three decades, the scope of solid-state NMR has expanded to exploring complex biomolecules, from large protein assemblies to intact cells at atomic-level resolution. This diversity in macromolecules frequently features highly flexible components whose insoluble environment precludes the use of solution NMR to study their structure and interactions. While High-resolution Magic-Angle Spinning (HR-MAS) probes offer the capacity for gradient-based 1H-detected spectroscopy in solids, such probes are not commonly used for routine MAS NMR experiments. As a result, most exploration of the flexible regime entails either 13C-detected experiments, the use of partially perdeuterated systems, or ultra-fast MAS. Here we explore proton-detected pulse schemes probing through-bond 13C–13C networks to study mobile protein sidechains as well as polysaccharides in a broadband manner. We demonstrate the use of such schemes to study a mixture of microtubule-associated protein (MAP) tau and human microtubules (MTs), and the cell wall of the fungus Schizophyllum commune using 2D and 3D spectroscopy, to show its viability for obtaining unambiguous correlations using standard fast-spinning MAS probes at high and ultra-high magnetic fields. [ABSTRACT FROM AUTHOR]

Amyloid fibrils are large and insoluble protein assemblies composed of a rigid core associated with a cross-β arrangement rich in β-sheet structural elements. It has been widely observed in solid-state NMR experiments that semi-rigid protein segments or side chains do not yield easily observable NMR signals at room temperature. The reasons for the missing peaks may be due to the presence of unfavorable dynamics that interfere with NMR experiments, which result in very weak or unobservable NMR signals. Therefore, for amyloid fibrils, semi-rigid and dynamically disordered segments flanking the amyloid core are very challenging to study. Here, we show that high-field dynamic nuclear polarization (DNP), an NMR hyperpolarization technique typically performed at low temperatures, can circumvent this issue because (i) the low-temperature environment (~ 100 K) slows down the protein dynamics to escape unfavorable detection regime, (ii) DNP improves the overall NMR sensitivity including those of flexible side chains, and (iii) efficient cross-effect DNP biradicals (SNAPol-1) optimized for high-field DNP (≥ 18.8 T) are employed to offer high sensitivity and resolution suitable for biomolecular NMR applications. By combining these factors, we have successfully established an impressive enhancement factor of ε ~ 50 on amyloid fibrils using an 18.8 T/ 800 MHz magnet. We have compared the DNP efficiencies of M-TinyPol, NATriPol-3, and SNAPol-1 biradicals on amyloid fibrils. We found that SNAPol-1 (with ε ~ 50) outperformed the other two radicals. The MAS DNP experiments revealed signals of flexible side chains previously inaccessible at conventional room-temperature experiments. These results demonstrate the potential of MAS-DNP NMR as a valuable tool for structural investigations of amyloid fibrils, particularly for side chains and dynamically disordered segments otherwise hidden at room temperature. [ABSTRACT FROM AUTHOR]