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As the main structural component of tobacco cell wall, lignin content is an important factor affecting the safety of tobacco smoking. However, it is time‐consuming to quantify lignin by conventional wet chemical analysis methods. In this work, a 13C multiCP/MAS NMR spectral analysis method for tobacco lignin was established. The multiCP/MAS NMR sequence was optimized for tobacco lignin. The optimized nuclear magnetic sequence parameters were 9 CP cycles of 1.5 ms, repolarization time of 0.7 s, and a total acquisition time of 130 min. Subsequently, TMSP was used as the internal standard substance to establish the working curve, and the correlation coefficient was 0.9946. The relative standard deviation (RSD, n = 5) was 3.26%. This method was applied to the determination of lignin content in different types of tobacco samples. The relative error in the determination of lignin content by this method did not exceed 4.46% compared to the results of the chemical method. The results showed that the 13C multiCP/MAS NMR spectral analysis method had the advantages of accuracy and rapidity, which provided a new technical means for the quantitative study of tobacco cell wall substances. [ABSTRACT FROM AUTHOR]

Ultra‐fast magic‐angle spinning (100+kHz) has revolutionized solid‐state NMR of biomolecular systems but has so far failed to gain ground for the analysis of paramagnetic organic and inorganic powders, despite the potential rewards from substantially improved spectral resolution. The principal blockages are that the smaller fast‐spinning rotors present significant barriers for sample preparation, particularly for air/moisture‐sensitive systems, and are associated with low sensitivity from the reduced sample volumes. Here, we demonstrate that the sensitivity penalty is less severe than expected for highly paramagnetic solids and is more than offset by the associated improved resolution. While previous approaches employing slower MAS are often unsuccessful in providing sufficient resolution, we show that ultra‐fast 100+kHz MAS allows site‐specific assignments of all resonances from complex paramagnetic solids. Combined with more reliable rotor materials and handling methods, this opens the way to the routine characterization of geometry and electronic structures of functional paramagnetic systems in chemistry, including catalysts and battery materials. We benchmark this approach on a hygroscopic luminescent Tb3+ complex, an air‐sensitive homogeneous high‐spin Fe2+ catalyst, and a series of mixed Fe2+/Mn2+/Mg2+ olivine‐type cathode materials. [ABSTRACT FROM AUTHOR]

ABSTRACT In solid‐state nuclear magnetic resonance (ssNMR) spectroscopy, fast magic angle spinning (MAS) is a potent technique that efficiently reduces line broadening and makes it possible to probe structural details of biological systems in high resolution. However, its utilization in studying complex heterogeneous biomaterials such as bone in their native state has been limited. The present study has demonstrated the feasibility of acquiring two‐dimensional (2D) 1H‐1H correlation spectra for native bone using multiple‐quantum/single‐quantum correlation experiments (MQ/SQ) at fast MAS (70 kHz). This method uncovered distinct 1H–1H dipolar coupling networks involving long‐chain charged residues of collagen protein, highlighting their role in maintaining the stability of the collagen triple helix. Our study opens up new avenues for 1H‐detected multi‐quantum‐based experiments at fast MAS on native collagen‐containing biological systems to explore their complex heterogeneous structural details more efficiently. [ABSTRACT FROM AUTHOR]

Anti-vascular endothelial growth factor (VEGF) drugs suppress choroidal neovascularisation (CNV), thus improving vision. However, some patients may have a poor response or develop resistance to anti-VEGF drugs. Geraniin (GE), a polyphenol isolated from an herb called Phyllanthus amarus, possesses anti-angiogenic properties. This study aimed to explore the mechanism of action of GE in CNV. GE was found to activate the angiotensin-converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang-[1-7])/MAS1 proto-oncogene, G protein-coupled receptor (MasR)/interleukin-10 (IL-10) pathway in hypoxic human choroidal endothelial cells (HCECs) in vitro and mouse models of laser-induced CNV in vivo. Activation of the ACE2/Ang-(1-7)/MasR/IL-10 pathway by GE attenuated the proliferative, migratory, and tube-forming abilities of hypoxic HCECs and prevented the development of CNV in mice. Notably, GE did not cause ocular or systemic toxicity in mice with CNV. These findings suggest that GE alleviates CNV by activating the ACE2/Ang-(1-7)/MasR/IL-10 pathway in choroidal endothelial cells (CECs)., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

ABSTRACT The purpose of this study was to develop and validate a new measurement tool designed to capture endorsement of myths surrounding female perpetrated sexual violence against men, specifically in ‘forced‐to‐penetrate’ cases. Data were collected among a sample of 4152 UK adults aged 18–55+ (52% female). Dimensionality and construct validity of the Forced‐to‐Penetrate Myth Acceptance Scale (FTP‐MAS) was investigated using traditional Confirmatory Factor Analysis (CFA) techniques separately for the complete sample, males only, and females only. CFA results indicated that FTP‐MAS scores are best captured by a three‐factor model (1. Distorted Sex and Gender Roles; 2. Harm Minimisation; 3. Offence Denial) across all samples tested. Excellent composite reliability and differential predictive validity were observed for all three subscales. The validated 22‐item FTP‐MAS constitutes the first measurement tool which allows for the assessment and evaluation of public attitudes towards female perpetrators who force men to penetrate them without consent. As such, this tool enables researchers to better understand the multi‐faceted nature of these myths, assess prevalence in different contexts, and can also be used as an outcome measure in research seeking to evaluate the effectiveness of interventions that aim to debunk endorsement of such myths and stereotypes. [ABSTRACT FROM AUTHOR]

Solid‐state NMR spectroscopy has gained increasing attention as a probe to investigate structures and dynamics of various solid materials, in particular, materials for rechargeable batteries. Cathodes and anodes for rechargeable batteries contain unpaired electrons (paramagnetic), which generate localized magnetic fields at molecules. Owing to this paramagnetic interaction, it is often complicated to measure and interpret the NMR spectra of the paramagnetic systems. Thus, understanding the effect of the interaction between unpaired electrons and nuclei is important. NMR spectroscopy at higher magnetic fields has been perceived as beneficial since this can provide higher sensitivity and resolution. However, the response to the magnetic field strength varies depending on the nuclei of interest and material properties because various factors affect NMR characteristics. In this work, we performed a systematic study of the effect of the field strength on the magic angle spinning (MAS) NMR characteristics by comparing diamagnetic and paramagnetic systems at two different magnetic fields. As diamagnetic materials, LiCoO2 (LCO) and Li2O are examined. As paramagnetic materials, LiFePO4(LFP) and lithium nickel manganese cobalt oxides (LiNixMnyCo1–x–yO2) with different compositions are investigated. We have demonstrated that higher signal intensity and narrower linewidths can be obtained at higher magnetic fields for diamagnetic systems, whereas higher signal intensity and better resolution are obtained at lower magnetic fields for paramagnetic systems. Our research will provide systematic and experimental evidence about the field strength dependence of paramagnetic systems and rationalized grounds for choosing proper NMR spectrometers for each material. [ABSTRACT FROM AUTHOR]

The metal–organic frameworks (MOFs) attract interest as potential catalysts whose catalytic properties are driven by defects. Several methods have been proposed for the defects‐inducing synthesis of MOFs. However, the active species formed on the defective sites remain elusive and uncharacterized, as the spectroscopic fingerprints of these species are hidden by the regular structure signals. In this work, we have performed the synthesis of ZIF‐8 MOF with defect‐inducing procedures using fully deuterated 2‐methylimidazolate ligands to enhance the defective sites′ visibility. By combining 1H and 31P MAS NMR spectroscopy and X‐ray absorption spectroscopy, we have found evidence for the presence of different structural hydroxyl Zn−OH groups in the ZIF‐8 materials. It is demonstrated that the ZIF‐8 defect sites are represented by Zn−OH hydroxyl groups with the signals at 0.3 and −0.7 ppm in the 1H MAS NMR spectrum. These species are of basic nature and may be responsible for the catalytic activity of the ZIF‐8 material. [ABSTRACT FROM AUTHOR]

Diminazene aceturate (DIZE) has been described as an angiotensin-converting enzyme 2 (ACE2) activator. We aimed to investigate DIZE effects on blood pressure (BP) of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. BP was recorded in awake and unrestrained rats 24 hours after femoral artery catheterization. DIZE (15 mg/kg, s.c.) produced a fast BP decrease only in SHR (P < .01). Pre-treatment with L-NAME (10 mg/kg, iv) did not change the hypotensive effect on systolic BP whereas mitigated the DIZE effect on diastolic BP (∆ Emax: -31 ± 5 DIZE vs -15 ± 1 mm Hg DIZE + L-NAME, P < .05). BP changes after DIZE remained unchanged after the treatment of rats with A-779 (50 ug/kg, iv), a Mas receptor blocker. Vasodilatation curves to DIZE (10 -9 to 10 -4  mol/L) in mesenteric arteries confirmed the NO-mediation on DIZE effects in SHR, as L-NAME (300 μmol/L) reduced the vascular sensitivity (∆EC50: -5.12 ± 0.09 CONTROL vs -4.66 ± 0.08 L-NAME, P < .05) and the magnitude of DIZE effect (area under the curve (AUC), 357.5 ± 8.2 DIZE vs 424.7 ± 11.6 L-NAME; P < .001), whereas A-779 (1 μmol/L) enhanced DIZE response (AUC, 357.5 ± 8.2 DIZE vs 309.8 ± 14.7 A-779, P < .05). Our findings indicate that DIZE acutely reduces the BP in SHR possibly by a mechanism other than Mas receptor activation. This effect seems to be mediated, at least partially, by NO., (© 2020 John Wiley & Sons Australia, Ltd.)

Chronic spontaneous urticaria (CSU), atopic dermatitis (AD), psoriasis and rosacea are highly prevalent inflammatory skin conditions which impose a significant burden on patients' quality of life. Their pathophysiology is likely multifactorial, involving genetic, immune and environmental factors. Recent advancements in the field have demonstrated the key role of mast cells (MC) in the pathophysiology of these conditions. The Mas-related G protein-coupled receptor X2 (MRGPRX2) has emerged as a promising non-IgE-mediated MC activation receptor. MRGPRX2 is predominately expressed on MC and activated by endogenous and exogenous ligands, leading to MC degranulation and release of various pro-inflammatory mediators. Mounting evidence on the presence of endogenous MRGPRX2 agonists (substance P, cortistatin-14, LL37, PAMP-12 and VIP) and its high expression among patients with CSU, AD, rosacea, psoriasis and chronic pruritus emphasizes the pathogenic role of MRGPRX2 in these conditions. Despite the currently available treatments, there remains a pressing need for novel drug targets and treatment options for these chronic inflammatory skin conditions. Here, we reviewed the pathogenic role of MRGPRX2 and its potential as a novel therapeutic target and provided an update on future research directions., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

The renin‐angiotensin system (RAS) is an endocrine system composed of two main axes: the classical and the counterregulatory, very often displaying opposing effects. The classical axis, primarily mediated by angiotensin receptors type 1 (AT1R), is linked to obesity‐associated metabolic effects. On the other hand, the counterregulatory axis appears to exert antiobesity effects through the activation of two receptors, the G protein‐coupled receptor (MasR) and Mas‐related receptor type D (MrgD). The local RAS in adipose organ has prompted extensive research into white adipose tissue and brown adipose tissue (BAT), with a key role in regulating the cellular and metabolic plasticity of these tissues. The MasR activation favors the brown plasticity signature in the adipose organ by improve the thermogenesis, adipogenesis, and lipolysis, decrease the inflammatory state, and overall energy homeostasis. The MrgD metabolic effects are related to the maintenance of BAT functionality, but the signaling remains unexplored. This review provides a summary of RAS counterregulatory actions triggered by Mas and MrgD receptors on adipose tissue plasticity. Focus on the effects related to the morphology and function of adipose tissue, especially from animal studies, will be given targeting new avenues for treatment of obesity‐associated metabolic effects. [ABSTRACT FROM AUTHOR]

Mas‐related G protein‐coupled receptor X2 (MrgprX2) is acknowledged as a mast cell‐specific receptor, playing a crucial role in orchestrating anaphylactoid responses through mast cell degranulation. It holds promise as a target for regulating allergic and inflammatory diseases mediated by mast cells. Polygonum cuspidatum (PC) has shown notable anti‐anaphylactoid effects, while its pharmacologically active components remain unclear. In this study, we successfully utilized MrgprX2 high‐expressing cell membrane chromatography (CMC), in conjunction with liquid chromatography‐mass spectrometry (LC‐MS), to identify active anti‐anaphylactoid components in PC. Our study pinpointed polydatin, resveratrol, and emodin‐8‐O‐β‐d‐glucoside as potential anti‐anaphylactoid compounds in PC. Their anti‐anaphylactoid activities were evaluated through β‐aminohexosidase and histamine release assays, demonstrating a concentration‐dependent inhibition for both β‐aminohexosidase and histamine release. This approach, integrating MrgprX2 high‐expression CMC with LC‐MS, proves effective in screening potential anti‐anaphylactoid ingredients in natural herbal medicines. The findings from this study illuminated the anti‐anaphylactoid properties of specific components in PC and provided an efficient method for the drug development of natural products. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic debilitating condition, hallmarked by persistent inflammation of the gastrointestinal tract. Despite recent advances in clinical treatments, the aetiology of IBD is unknown, and a large proportion of patients are refractory to pharmacotherapy. Understanding IBD immunopathogenesis is crucial to discern the cause of IBD and optimise treatments. Mas‐related G protein‐coupled receptors (Mrgprs) are a family of approximately 50 G protein‐coupled receptors that were first identified over 20 years ago. Originally known for their expression in skin nociceptors and their role in transmitting the sensation of itch in the periphery, new reports have described the presence of Mrgprs in the gastrointestinal tract. In this review, we consider the impact of these findings and assess the evidence that suggests that Mrgprs may be involved in the disrupted homeostatic processes that contribute to gastrointestinal disorders and IBD. LINKED ARTICLES: This article is part of a themed issue Therapeutic Targeting of G Protein‐Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc [ABSTRACT FROM AUTHOR]

Lattice strain engineering optimizes the interaction between the catalytic surface and adsorbed molecules. This is done by adjusting the electron and geometric structure of the metal site to achieve high electrochemical performance, but, to date, it has been rarely reported on anti‐poisoned oxygen reduction reaction (ORR). Herein, lattice‐strained Pd@PdBiCo quasi core‐shell metallic aerogels (MAs) were designed by "one‐pot and two‐step" method for anti‐poisoned ORR. Pd@PdBiCo MAs/C maintain their original activity (1.034 A mgPd−1) in electrolytes with CH3OH and CO at 0.85 V vs. reversible hydrogen electrode (RHE), outperforming the commercial Pd/C (0.156 A mgPd−1), Pd MAs/C (0.351 A mgPd−1), and PdBiCo MAs/C (0.227 A mgPd−1). Moreover, Pd@PdBiCo MAs/C also show high stability and anti‐poisoning with negligible activity decay after 8000 cycles in 0.1 m KOH+0.3 m CH3OH. These results of X‐ray photoelectron spectroscopy, CO stripping, and diffuses reflectance FTIR spectroscopy reveal that the tensile strain and strong interaction between different elements of Pd@PdBiCo MAs/C effectively optimize the electronic structure to promote O2 adsorption and activation, while suppressing CH3OH oxidation and CO adsorption, leading to high ORR activity and anti‐poisoning property. This work inspires the rational design of MAs in fuel cells and beyond. [ABSTRACT FROM AUTHOR]

Cornelian cherry (CC) is a source of bioactive compounds such as phenolics, melatonin and, vitamin C and used as traditional food and in folk medicine. In this study, we analyzed and compared the variation of some bioactive compounds and antioxidant capacity in CC fruits depending on ripening and genotype. CC fruit was sampled at different ripening times (unripe, semi‐ripe and ripe) and the contents of sugars, vitamin C, melatonin and phenolic compounds were analysed by ultra‐fast liquid chromatography (UFLC‐PDA). The results showed that the fruits at the unripe samples had a significantly higher chemical components and antioxidant capacity. Chlorogenic acid, catechin, gallic acid and rutin were the four major phenolic compounds identified in all genotypes. Melatonin concentration of unripe fruits was found to be high in all genotypes (ranged from 1664.78–114.60 ng/mL) and a decrease was detected in ripe fruits. Significant increases in vitamin C and individual sugar contents (glucose and fructose) occurred with advancing maturity. The highest vitamin C concentration was determined as 77.38 mg/100 g during the full ripening period. Antioxidant capacity results determined by both methods showed a decreasing tendency with the ripening of the fruits. Concerning antioxidant activity, DPPH and ABTS scavenging activity were maximal at unripe in all CC genotpes. During the development and maturity periods of fruits, important physiological and biochemical changes occured that affect antioxidant capacity, nutritional and chemical composition. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the effect on the anthropometric and biochemical parameters for women with insulin resistance when lyophilized dried cornelian cherry (Cornus mas L., CM) was added to medical nutrition therapy (MNT). The study was conducted with 84 women aged 18–45, who had been diagnosed with insulin resistance. Participants were randomized into four groups: MNT + 20 g lyophilized dried CM group (DCm, n = 22), MNT group (D, n = 21), only 20 g lyophilized dried CM group (Cm, n = 21), and the control group (C, n = 20). All participants were followed for 12 weeks. While pre‐ and post‐intervention biochemical parameters were recorded from patient files, anthropometric measurements and food consumption records were taken every 15 days. Pre‐intervention groups were homogeneously distributed. Post‐intervention, among the groups, all anthropometric measurements were similar between the DCm and D, while the percentage of decrease in insulin resistance‐related parameters was approximately two times greater in DCm than in D (p <.05). When the Cm and C were compared, it was found that all post‐intervention anthropometric measurements were similar, but the percentage of decrease in fasting blood glucose, fasting insulin, and HOMA‐IR (Homeostasis Model Assessment‐Insulin Resistance) values were greater in C (p <.05). In this study, it was concluded that CM consumption resulted with a decrease in insulin resistance‐related biochemical parameters independent of body weight change. Nevertheless, MNT has positive effects on women with insulin resistance, and adding lyophilized dried CM to MNT improves insulin resistance‐related parameters and may be beneficial for preventing the development of diabetes. [ABSTRACT FROM AUTHOR]

Acetaminophen overdose is a leading cause of acute liver failure (ALF). Despite the pivotal role of the inflammatory microenvironment in the progression of advanced acetaminophen‐induced liver injury (AILI), a comprehensive understanding of the underlying cellular interactions and molecular mechanisms remains elusive. Mas is a G protein‐coupled receptor highly expressed by myeloid cells; however, its role in the AILI microenvironment remains to be elucidated. A multidimensional approach, including single‐cell RNA sequencing, spatial transcriptomics, and hour‐long intravital imaging, is employed to characterize the microenvironment in Mas1 deficient mice at the systemic and cell‐specific levels. The characteristic landscape of mouse AILI models involves reciprocal cellular communication among MYC+CD63+ endothelial cells, MMP12+ macrophages, and monocytes, which is maintained by enhanced glycolysis and the NF‐κB/TNF‐α signaling pathway due to myeloid‐Mas deficiency. Importantly, the pathogenic microenvironment is delineated in samples obtained from patients with ALF, demonstrating its clinical relevance. In summary, these findings greatly enhance the understanding of the microenvironment in advanced AILI and offer potential avenues for patient stratification and identification of novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Objective: To improve our understanding of systemic lupus erythematosus (SLE)‐macrophage activation syndrome (MAS). Methods: A systematic review was performed, to retrieve all those papers on patients with SLE‐MAS, in individual or aggregated form. The data in each of these medical records were extracted and analyzed to identify the characteristics of SLE‐MAS. Results: A total of 86 SLE‐MAS patients were included (25 males and 61 females. The mean (±standard error of the mean) age was 31.21 ± 1.694 years. MAS occurred as the initial presentation of SLE in 47 people (54.65%) and during the course of SLE in 39 (45.35%). A coinfection was reported in 23 (26.74%) patients. The mean Lupus Erythematosus Disease Activity Index 2000 (SLEDAI‐2K) score was 16.54 ± 0.9462. Overall, 10 patients (11.63%) died. The SLEDAI‐2K score was higher in patients with MAS as an initial manifestation of SLE than in those where MAS occurred during the course of SLE. The proportion of patients receiving steroid pulse therapy was lower in patients with coinfections. The deceased group demonstrated lower platelet and ferritin levels. Multiple regression analysis revealed that age and thrombocytopenia were independent factors associated with poor prognosis. In receiver operating characteristic analysis, a platelet count cutoff value of ≤47 × 109/L was a predictor of poor outcome. Conclusions: SLE‐MAS patients demonstrated high lupus activity, and lupus activity was especially higher in patients with MAS as an initial manifestation. Lupus activity was the predominant trigger of lupus MAS. Thrombocytopenia was an independent factor for poor prognosis. Highlights: Lupus activity was especially high in patients with macrophage activation syndrome (MAS) as an initial manifestation.Lupus activity is the predominant trigger for lupus‐MAS.Thrombocytopenia is a predictor of poor prognosis in patients with systemic lupus erythematosus‐MAS. [ABSTRACT FROM AUTHOR]

This study aims to analyse the impact of the Movement towards Socialism (MAS) regime on GDP, income inequality and corruption levels. The empirical findings show that GDP has increased and corruption decreased with the MAS party in power. Income inequality, however, has tended to increase, even though average values for the Gini index during the MAS years have been lower. The difference between counterfactual and actual observations (i.e. treatment effects) was regressed against three key shocks experienced by the Bolivian economy and the findings demonstrate that all these shocks are correlated with the three outcome variables. [ABSTRACT FROM AUTHOR]

To identify the mechanism underlying macrosteatosis (MaS)‐related graft failure (GF) in liver transplantation (LT) by multi‐omics network analysis. The transcriptome and metabolome were assayed in graft and recipient plasma in discovery (n = 68) and validation (n = 89) cohorts. Differentially expressed molecules were identified by MaS and GF status. Transcriptional regulatory networks were generated to explore the mechanism for MaS‐related inferior post‐transplant prognosis. The differentially expressed molecules associated with MaS and GF were enriched in ferroptosis and peroxisome‐related pathways. Core features of MaS‐related GF were presented on decreased transferrin and impaired anti‐oxidative capacity dependent upon dysregulation of transcription factors hepatocyte nuclear factor 4A (HNF4A) and hypoxia‐inducible factor 1A (HIF1A). Furthermore, miR‐362‐3p and miR‐299‐5p inhibited transferrin and HIF1A expression, respectively. Lower M2 macrophages but higher memory CD4 T cells were observed in MaS‐related GF cases. These results were validated in clinical specimens and cellular models. Systemic analysis of multi‐omics data depicted a panorama of biological pathways deregulated in MaS‐related GF. Transcriptional regulatory networks centered on transferrin and anti‐oxidant responses were associated with poor MaS graft quality, qualifying as potential targets to improve prognosis of patients after LT. [ABSTRACT FROM AUTHOR]

Background The activation of AT2 (angiotensin II type 2 receptor ) and Mas receptor by angiotensin II and angiotensin-(1-7), respectively, is the primary process that counteracts activation of the canonical renin-angiotensin system (RAS). Although inhibition of canonical RAS could delay the progression of physiological aging, we recently reported that deletion of Mas had no impact on the aging process in mice. Here, we used male mice with a deletion of only AT2 or a double deletion of AT2 and Mas to clarify whether these receptors contribute to the aging process in a complementary manner, primarily by focusing on aging-related muscle weakness. Methods and Results Serial changes in grip strength of these mice up to 24 months of age showed that AT2/Mas knockout mice, but not AT2 knockout mice, had significantly weaker grip strength than wild-type mice from the age of 18 months. AT2/Mas knockout mice exhibited larger sizes, but smaller numbers and increased frequency of central nucleation (a marker of aged muscle) of single skeletal muscle fibers than AT2 knockout mice. Canonical RAS-associated genes, inflammation-associated genes, and senescence-associated genes were highly expressed in skeletal muscles of AT2/Mas knockout mice. Muscle angiotensin II content increased in AT2/Mas knockout mice. Conclusions Double deletion of AT2 and Mas in mice exaggerated aging-associated muscle weakness, accompanied by signatures of activated RAS, inflammation, and aging in skeletal muscles. Because aging-associated phenotypes were absent in single deletions of the receptors, AT2 and Mas could complement each other in preventing local activation of RAS during aging.

This research letter discusses the potential use of MRGPRX2 and CCL-2 as biomarkers for chronic spontaneous urticaria (CSU) in Chinese patients. The study found that serum MRGPRX2 levels were higher in patients with severe disease compared to nonsevere disease, and that MRGPRX2 was more useful in treatment-naïve patients. Additionally, CCL-2 levels were found to be elevated in patients with severe disease. The study suggests that both MRGPRX2 and CCL-2 may be potential biomarkers for CSU, but further research is needed to validate these findings. [Extracted from the article]

Angiotensin-converting enzyme-2 (ACE2) and Mas receptor are the major components of the ACE2/Ang 1-7/Mas axis and have been shown to play a protective role in hypertension and hypertensive nephropathy individually. However, the effects of dual deficiency of ACE2 and Mas (ACE2/Mas) on Ang II-induced hypertensive nephropathy remain unexplored, which was investigated in this study in a mouse model of hypertension induced in either ACE2 knockout (KO) or Mas KO mice and in double ACE2/Mas KO mice by subcutaneously chronic infusion of Ang II. Compared with wild-type (WT) animals, mice lacking either ACE2 or Mas significantly increased blood pressure over 7-28 days following a chronic Ang II infusion (P < .001), which was further exacerbated in double ACE2/Mas KO mice (P < .001). Furthermore, compared to a single ACE2 or Mas KO mice, mice lacking ACE2/Mas developed more severe renal injury including higher levels of serum creatinine and a further reduction in creatinine clearance, and progressive renal inflammation and fibrosis. Mechanistically, worsen hypertensive nephropathy in double ACE2/Mas KO mice was associated with markedly enhanced AT1-ERK1/2-Smad3 and NF-κB signalling, thereby promoting renal fibrosis and renal inflammation in the hypertensive kidney. In conclusion, ACE2 and Mas play an additive protective role in Ang II-induced hypertension and hypertensive nephropathy. Thus, restoring the ACE2/Ang1-7/Mas axis may represent a novel therapy for hypertension and hypertensive nephropathy., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life‐threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence‐based and consensus‐based points to consider to assist clinicians in optimising decision‐making in the early stages of diagnosis, treatment and monitoring of HLH/MAS. Methods: A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision‐making and optimising the initial care of patients with HLH/MAS. Results: The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance. Conclusion: These 2022 EULAR/American College of Rheumatology points to consider provide up‐to‐date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life‐threatening immunopathology. [ABSTRACT FROM AUTHOR]

DC microgrids (DCMGs) have significant advantages, but their protection can be a challenge for DCMGs expansion expressly in distributed generation sources' (DGS) tendance. This paper proposes a quick, and precise strategy to perceive and trip any fault in DCMGs in the free tendance of DGS. A bi‐level multi‐agent system (MAS) is proposed to protect the DCMG and DGs. The MAS first level perceives the fault in DCMG via a discrete wavelet transform (DWT). The multiply of two harvest levels' summation of DWT is exerted to detect and distinguish DC lines faults. The MAS second level detects the fault in DGS and their switchers to the point of common connection (PCC) via a differential pole (DP) controller. A four bus DCMG containing solar PV and wind sources is implemented, and the results demonstrate that the proposed plan can recognize and trip the fault by 100% of reliability. [ABSTRACT FROM AUTHOR]

Can commodity polymers are made to be healable just by blending with self‐healable polymers? Here we report the first study on the fundamental aspect of this practically challenging issue. Poly(ether thiourea) (PTUEG3; Tg=27 °C) reported in 2018 is extraordinary in that it is mechanically robust but can self‐heal even at 12 °C. In contrast, poly(octamethylene thiourea) (PTUC8; Tg=50 °C), an analogue of PTUEG3, cannot heal below 92 °C. We found that their polymer blend self‐healed in a temperature range above 32 °C even when its PTUEG3 content was only 20 mol %. Unlike PTUEG3 alone, this polymer blend, upon exposure to high humidity, barely plasticized, keeping its excellent mechanical properties due to the non‐hygroscopic nature of the PTUC8 component. CP/MAS 13C NMR analysis revealed that the polymer blend was nanophase‐separated, which possibly accounts for why such a small amount of PTUEG3 provided the polymer blend with humidity‐tolerant self‐healable properties. [ABSTRACT FROM AUTHOR]

In the devastating rice blast fungus Magnaporthe oryzae, six Magnaporthe appressoria‐specific (MAS) proteins are encoded by MoGAS1, MoGAS2 and MoMAS3–MoMAS6. MoGAS1 and MoGAS2 were previously characterized as M. oryzae virulence factors; however, the roles of the other four genes are unknown. Here, we found that, although the loss of any MAS gene did not affect appressorial formation or vegetative growth, ∆Momas3 and ∆Momas5 mutant strains (but not the others) were reduced in virulence on susceptible CO‐39 rice seedlings. Focusing on ∆Momas3 and ∆Momas5 mutant strains, we found that they could penetrate host leaf surfaces and fill the first infected rice cell but did not spread readily to neighbouring cells, suggesting they were impaired for biotrophic growth. Live‐cell imaging of fluorescently labelled MoMas3 and MoMas5 proteins showed that during biotrophy, MoMas3 localized to the apoplastic compartment formed between fungal invasive hyphae and the plant‐derived extra‐invasive hyphal membrane while MoMas5 localized to the appressoria and the penetration peg. The loss of either MoMAS3 or MoMAS5 resulted in the accumulation of reactive oxygen species (ROS) in infected rice cells, resulting in the triggering of plant defences that inhibited mutant growth in planta. ∆Momas3 and ∆Momas5 biotrophic growth could be remediated by inhibiting host NADPH oxidases and suppressing ROS accumulation. Thus, MoMas3 and MoMas5 are novel virulence factors involved in suppressing host plant innate immunity to promote biotrophic growth. [ABSTRACT FROM AUTHOR]

The sensitivity of NMR spectroscopy is considerably enhanced by dynamic nuclear polarization (DNP). In DNP polarization is transferred from unpaired electrons of a polarizing agent to nearby proton spins. In solids, this transfer is followed by the transport of hyperpolarization to the bulk via 1H‐1H spin diffusion. The efficiency of these steps is critical to obtain high sensitivity gains, but the pathways for polarization transfer in the region near the unpaired electron spins are unclear. Here we report a series of seven deuterated and one fluorinated TEKPol biradicals to probe the effect of deprotonation on MAS DNP at 9.4 T. The experimental results are interpreted with numerical simulations, and our findings support that strong hyperfine couplings to nearby protons determine high transfer rates across the spin diffusion barrier to achieve short build‐up times and high enhancements. Specifically, 1H DNP build‐up times increase substantially with TEKPol isotopologues that have fewer hydrogen atoms in the phenyl rings, suggesting that these protons play a crucial role transferring the polarization to the bulk. Based on this new understanding, we have designed a new biradical, NaphPol, which yields significantly increased NMR sensitivity, making it the best performing DNP polarizing agent in organic solvents to date. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study? What are the effects of the antifibrotic peptide acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas axis during the occurrence and progression of silicosis? What is the main finding and its importance? Ac-SDKP inhibited lung fibrosis in rats exposed to silica by activation of the ACE2-angiotensin-(1-7)-Mas axis. Angiotensin-(1-7) potentially promotes Ac-SDKP by increasing the level of meprin α, the major synthetase of Ac-SDKP. Thus, the interaction Ac-SDKP and angiotesin-(1-7) in silicosis could provide a new therapeutic strategy., Abstract: The central role of angiotensin-converting enzyme (ACE) in the occurrence and progression of silicosis has been established. The antifibrotic peptide acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) can be degraded by ACE. The ACE2-angiotensin-(1-7)-Mas axis is protective and acts to counterbalance the detrimental effects of ACE-angiotensin II (Ang II)-Ang II type 1 receptor and exerts antifibrotic effects. Here, we demonstrate an interaction between Ac-SDKP and Ang-(1-7) in the inhibition of collagen deposition and myofibroblast differentiation in rats exposed to silica. Treatment with Ac-SDKP increased the level of ACE2-Ang-(1-7)-Mas in rats or in cultured fibroblasts and decreased the levels of collagen type I and α-smooth muscle actin. Furthermore, exogenous Ang-(1-7) had similar antifibrotic effects and increased the level of meprin α, a major Ac-SDKP synthetase, both in vivo and in vitro. Compared with non-silicotic patients exposed to silica, the level of serum ACE was increased in patients with silicosis phase III; the levels of Ang II and Ang-(1-7) were high in patients with silicosis phase II; and the level of Ac-SDKP was high in the silicosis phase III group. These data imply that Ac-SDKP and Ang-(1-7) have an interactive effect as regulatory peptides of the renin-angiotensin system and exert antifibrotic effects., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

A type of boron nitride–magnesium aluminum silicate (BN‐MAS) composite ceramics was fabricated by hot‐press sintering at different sintering temperatures. The relationship between the sintering temperature and microstructure was investigated by analyzing the interaction between hexagonal boron nitride (h‐BN) and the MAS phase. The main MAS phase in the composite ceramics is the α‐cordierite phase at a sintering temperature of 1300°C. At temperatures above 1400°C, the inhibitory effect of h‐BN on the crystallization of the MAS system is significant, and MAS mainly exists in the form of an amorphous phase. The composite sintered at 1700°C exhibited the highest bending strength of 218MPa. h‐BN and MAS were co‐enhanced. MAS can be used as an effective liquid‐phase sintering aid to assist in the sintering of h‐BN, whereas h‐BN can absorb the fracture energy of the composite ceramics through the pull‐out and bridging effect of the particles. [ABSTRACT FROM AUTHOR]

Morphea, an autoimmune connective tissue disease that affects the skin, can be supported by color Doppler ultrasound in its diagnosis and assessment of activity. To date, there are no reliable laboratory parameters to track activity, and ultrasound presents a higher axial spatial resolution than magnetic resonance imaging and computed tomography, which is critical for studying the superficial layers. The quality of the ultrasonographic assessment of activity in morphea depends on the standardization and features of the acquisition of the anatomical data. We propose a detailed ultrasound morphea activity scoring called modified US‐MAS (mUS‐MAS) that could allow us to systematically register the cutaneous abnormalities in the corporal regions and their subregions. The selection of the scanning sites will depend on the corporal regions of involvement and their adjacent segments. Through systematic and sequential ultrasound data analysis, we propose that this scoring system can better support description and activity tracking accuracy. [ABSTRACT FROM AUTHOR]

Methylarsenite (MAs(III)), a product of arsenic biomethylation or bioreduction of methylarsenate (MAs(V)), has been proposed as a primitive antibiotic. However, the antibacterial property and the bactericidal mechanism of MAs(III) remain largely unclear. In this study, we found that MAs(III) is highly toxic to 14 strains of bacteria, especially against 9 strains of Gram‐positive bacteria with half maximal inhibitory concentration (IC50) in the sub micromolar range for Staphyloccocus aureus, Microbacterium sp., Pseudarthrobacter siccitolerans and several Bacillus species. In a co‐culture of B. subtilis 168 and MAs(III)‐producer Enterobacter sp. CZ‐1, the later reduced non‐toxic MAs(V) to highly toxic MAs(III) to kill the former and gain a competitive advantage. MAs(III) induced autolysis of B. subtilis 168. Deletion of the autolysins LytC, LytD, LytE, and LytF suppressed MAs(III)‐induced autolysis in B. subtilis 168. Transcriptomic analysis showed that MAs(III) downregulated the expression of the major genes involved in the biosynthesis of the cell wall peptidoglycan. Overexpression of an UDP‐N‐acetylglucosamine enolpyruvyl transferase gene murAA alleviated MAs(III)‐induced autolysis in B. subtilis 168. MAs(III) disrupted the membrane potential of B. subtilis 168 and caused severe membrane damage. The results suggest that MAs(III) is a broad‐spectrum antibiotic preferentially against Gram‐positive bacteria by disrupting the cell wall biosynthesis pathway and cell membrane potential. [ABSTRACT FROM AUTHOR]

Background: Stroke frequently leads to hospital admission and subsequent rehabilitation in order to overcome poststroke sequelae, such as motor impairments. Efficient planning of the steps following hospital admission includes early prediction of whether the patient can be discharged home or not. Early assessment of motor performance in patients with stroke‐induced motor deficits may be able to function as a predictor of discharge destination but is less explored. Objective: The primary objective was to assess the predictive validity of the Motor Assessment Scale (MAS) on discharge destination both regarding total score and regarding subscores (transfer‐mobility items and upper extremity items). Design: The study was designed as a prospective cohort study. Subjects: Thirty‐seven consecutively recruited patients with stroke are the subjects of the study. Methods: Logistic regression model was used to calculate the odds of being discharged to own home upon hospital admittance. The predictive ability was examined with a receiving operator characteristic (ROC) curve, and cut‐points from the curve were employed in Cox regression. Results: A one‐unit higher score on the total MAS significantly increased the odds of being discharged home upon hospital admittance (odds ratio (OR) 1.14, 95% CI 1.04–1.25). The same pattern was observed with the summed items of 1–5 and 6–8. The total MAS showed sensitivity of 91.7% and specificity of 68.0%. Patients having a total MAS score ≥ 24 were 17 times more likely to be discharged home (HR 17.64, 95% CI 2.23–139.57) compared to patients with a lower score. Conclusion: Motor function measured by the MAS can be applied as a predictor of discharge destination upon hospital admission after stroke in Danish setting. [ABSTRACT FROM AUTHOR]

Over the past decade, halogenated semiconducting polymers have attracted considerable interest due to their outstanding optoelectronic properties. Thus, in most of today's organic photovoltaic devices benchmark organic semiconductors are halogenated materials, either electron donor polymers or non‐fullerene acceptor (NFA) small molecules. However, the nature and position of the substituted halogen atoms in halogenated semiconducting polymers impact, through self‐assembly modification, their optoelectronic properties in a way that is difficult to predict. Yet, the solid‐state self‐assembling of these materials has been shown to be a key parameter toward high charge transport properties and photovoltaic efficiencies. In this context, there is still a need to develop analytical methods that will enable an atomic‐scale structural characterization of these materials as a function of the halogenation. In this study, the solid‐state nuclear magnetic resonance (NMR) under magic angle spinning (MAS) is explored as a tool to investigate the local structure and supramolecular organization of a series of conjugated polymers, specially designed for this study. Through a comprehensive study using complementary techniques, including MAS–NMR, small and wide‐angle X‐ray scattering, and molecular modeling investigations, the molecular conformation of these polymers in relation to their chemical composition, is successfully determined. [ABSTRACT FROM AUTHOR]

Background: Little is known about the features of macrophage activation syndrome (MAS) in dermatomyositis, especially the association between rapidly progressive interstitial lung disease (RP‐ILD) and MAS. Objective: To determine the characteristics of MAS in patients with dermatomyositis and their association with RP‐ILD. Methods: This was a retrospective cohort study of 201 dermatomyositis patients at the First Affiliated Hospital of Zhejiang University over a 10‐year period. Results: A total of 22 (10.9%) patients were diagnosed with MAS. The rate of RP‐ILD was significantly higher in patients with MAS than in those without MAS (81.8% vs. 17.4%, respectively, p <.001). Multivariate analysis indicated that RP‐ILD (p =.019), ferritin level > 1685 ng/mL (p =.007) and hemoglobin < 100 g/L (p =.001) were independent risk factors for MAS. Furthermore, RP‐ILD patients with MAS presented more cardiac injury (50.0% vs. 13.3%, respectively, p <.009), central nervous system dysfunction (42.8% vs. 3.4%, respectively, p <.001) and hemorrhage (38.9% vs. 3.3%, respectively, p =.003) than RP‐ILD patients without MAS. The 90‐day cumulative survival rate for patients with MAS was significantly lower than for those without MAS (18.2% vs. 82.1%, respectively, p <.001). Conclusion: MAS was a common and fatal complication of dermatomyositis in our cohort. MAS is closely related to RP‐ILD in patients with dermatomyositis. When RP‐ILD is present in dermatomyositis patients with abnormal laboratory findings, such as cytopenia and hyperferritinemia, the presence of MAS should be considered. Highlights: This study adds evidence that macrophage activation syndrome (MAS) is a common and fatal complication of adult dermatomyositis in our cohort. MAS is closely related to RP‐ILD in patients with dermatomyositis.Clinicians should be aware that when RP‐ILD is present in dermatomyositis patients with abnormal laboratory findings, such as cytopenia and hyperferritinemia, the presence of MAS should be considered. [ABSTRACT FROM AUTHOR]

The MrgD receptor agonist, alamandine (ALA) and Mas receptor agonist, AVE0991 have recently been identified as protective components of the renin‐angiotensin system. We evaluated the effects of ALA and AVE0991 on cardiovascular function and remodeling in angiotensin (Ang) II‐induced hypertension in rats. Sprague Dawley rats were subject to 4‐week subcutaneous infusions of Ang II (80 ng/kg/min) or saline after which they were treated with ALA (50 μg/kg), AVE0991 (576 μg/kg), or ALA+AVE0991 during the last 2 weeks. Systolic blood pressure (SBP) and heart rate (HR) values were recorded with tail‐cuff plethysmography at 1, 15, and 29 days post‐treatment. After euthanization, the heart and thoracic aorta were removed for further analysis and vascular responses. SBP significantly increased in the Ang II group when compared to the control group. Furthermore, Ang II also caused an increase in cardiac and aortic cyclophilin‐A (CYP‐A), monocyte chemoattractant protein‐1 (MCP‐1), and cardiomyocyte degeneration but produced a decrease in vascular relaxation. HR, matrix metalloproteinase‐2 and ‐9, NADPH oxidase‐4, and lysyl oxidase levels were comparable among groups. ALA, AVE0991, and the drug combination produced antihypertensive effects and alleviated vascular responses. The inflammatory and oxidative stress related to cardiac MCP‐1 and CYP‐A levels decreased in the Ang II+ALA+AVE0991 group. Vascular but not cardiac angiotensin‐converting enzyme‐2 levels decreased with Ang II administration but were similar to the Ang II+ALA+AVE0991 group. Our experimental data showed the combination of ALA and AVE0991 was found beneficial in Ang II‐induced hypertension in rats by reducing SBP, oxidative stress, inflammation, and improving vascular responses. [ABSTRACT FROM AUTHOR]

Background: The classical renin-angiotensin system is known as the angiotensin (Ang)-converting enzyme/Ang II/Ang type 1 receptor axis, which induces various organ damage including cognitive decline. The angiotensin-converting enzyme 2/Ang-(1-7)/Mas axis is known to exert antagonistic actions against the classical renin-angiotensin system axis in the cardiovascular system. However, its roles in the brain remain unclear. We examined possible roles of the angiotensin-converting enzyme 2/Ang-(1-7)/Mas axis in cognitive function, employing vascular cognitive impairment model mice., Methods and Results: Male 10-week-old C57BL6 (wild-type mice, Mas1 knockout mice, Ang II type 2 receptor knockout mice, and Ang II type 2 receptor/Mas1 double knockout mice were subjected to bilateral carotid artery stenosis (BCAS) surgery. Six weeks after treatment, they were subjected to cognitive tasks. Brain samples were used for histopathological analysis. Cognitive function was significantly impaired in wild-type and double knockout mice after BCAS. On the other hand, the cognitive function of Mas1 knockout mice was maintained in spite of the reduction of cerebral blood flow with BCAS. Total cell number in the dentate gyrus region was significantly reduced after BCAS in wild-type but not in Mas1 knockout mice. The number of doublecortin-positive cells in the subgranular zone was not significantly different between wild-type and Mas1 knockout mice. Ang-(1-7) administration did not improve cognitive function in all mice after BCAS surgery., Conclusions: Lack of the Mas receptor may have a protective effect against chronic brain ischemia when the Ang II type 2 receptor exists., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

In situ MAS NMR studies on the monitoring of hydrothermal synthesis of zeolites are reviewed. The first part of the review contains information on the experimental techniques used for the in situ NMR studies in static and MAS conditions. In the second part, the main capabilities of the in situ 1H, 11B, 13C, 14N, 19F, 23Na, 27Al, 29Si and 31P MAS NMR for the elucidation of the mechanism of hydrothermal synthesis of zeolites are examined and the data on NMR lines identification are summarized. In the last part the main application areas of the techniques are considered and illustrated with examples taken from the mechanistic studies of zeolites A, X, MFI and BEA synthesis. A cross‐reference index between the materials studied, the experimental approaches used, the mechanistic information obtained, and the corresponding literature sources is established. [ABSTRACT FROM AUTHOR]

Current microcoil probe technology has emerged as a significant advancement in NMR applications to biofluids research. It has continued to excel as a hyphenated tool with other prominent microdevices, opening many new possibilities in multiple omics fields. However, this does not hold for biological samples such as intact tissue or organisms, due to the considerable challenges of incorporating the microcoil in a magic‐angle spinning (MAS) probe without relinquishing the high‐resolution spectral data. Not until 2012 did a microcoil MAS probe show promise in profiling the metabolome in a submilligram tissue biopsy with spectral resolution on par with conventional high‐resolution MAS (HR‐MAS) NMR. This result subsequently triggered a great interest in the possibility of NMR analysis with microgram tissues and striving toward the probe development of "high‐resolution" capable microcoil MAS NMR spectroscopy. This review gives an overview of the issues and challenges in the probe development and summarizes the advancements toward metabolomics. [ABSTRACT FROM AUTHOR]

Efficiently hyperpolarizing proton‐dense molecular solids through dynamic nuclear polarization (DNP) solid‐state NMR is still an unmet challenge. Polarizing agents (PAs) developed so far do not perform well on proton‐rich systems, such as organic microcrystals and biomolecular assemblies. Herein we introduce a new PA, cAsymPol‐POK, and report outstanding hyperpolarization efficiency on 12.76 kDa U‐13C,15N‐labeled LecA protein and pharmaceutical drugs at high magnetic fields (up to 18.8 T) and fast magic angle spinning (MAS) frequencies (up to 40 kHz). The performance of cAsymPol‐POK is rationalized by MAS‐DNP simulations combined with electron paramagnetic resonance (EPR), density functional theory (DFT) and molecular dynamics (MD). This work shows that this new biradical is compatible with challenging biomolecular applications and unlocks the rapid acquisition of 13C–13C and 15N–13C correlations of pharmaceutical drugs at natural isotopic abundance, which are key experiments for structure determination. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study? Dietary sodium manipulation alters the magnitude of angiotensin-(1-7) [Ang-(1-7)]-induced natriuresis. The present study sought to determine whether this was related to relative changes in the activity of intrarenal Mas and/or AT 1 receptors. What is the main finding and its importance? Angiotensin-(1-7)-induced diuresis and natriuresis is mediated by intrarenal Mas receptors. However, intrarenal AT 1 receptor blockade also had an inhibitory effect on Ang-(1-7)-induced natriuresis and diuresis. Thus, Ang-(1-7)-induced increases in sodium and water excretion are dependent upon functional Mas and AT 1 receptors. We investigated whether angiotensin-(1-7) [Ang-(1-7)]-induced renal haemodynamic and excretory actions were solely dependent upon intrarenal Mas receptor activation or required functional angiotensin II type 1 (AT 1 ) receptors. The renin-angiotensin system was enhanced in anaesthetized rats by prior manipulation of dietary sodium intake. Angiotensin-(1-7) and AT 1 and Mas receptor antagonists were infused into the kidney at the corticomedullary border. Mas receptor expression was measured in the kidney. Mean arterial pressure, urine flow and fractional sodium excretion were 93 ± 4 mmHg, 46.1 ± 15.7 μl min -1  kg -1 and 1.4 ± 0.3%, respectively, in the normal-sodium group and 91 ± 2 mmHg, 19.1 ± 3.3 μl min -1  kg -1 and 0.7 ± 0.2%, respectively, in the low-sodium group. Angiotensin-(1-7) infusion had no effect on mean arterial pressure in rats receiving a normal-sodium diet but decreased it by 4 ± 5% in rats receiving a low-sodium diet (P < 0.05). Interstitial Ang-(1-7) infusion increased urine flow twofold and fractional sodium excretion threefold (P < 0.05) in rats receiving a normal-sodium diet and to a greater extent, approximately three- and fourfold, respectively, in rats receiving the low-sodium diet (both P < 0.05). Angiotensin-(1-7)-induced increases in urine flow and fractional sodium excretion were absent in both dietary groups during intrarenal AT 1 or Mas receptor inhibition after either losartan or A-779, respectively. Thus, AT 1 receptor activation, as well as Mas receptor activation, plays an essential role in mediating Ang-(1-7)-induced natriuresis and diuresis. Whether this is because Ang-(1-7) partly antagonizes AT 1 receptors or whether Ang-(1-7)-induced natriuresis is mediated through AT 1 -Mas receptor dimerization remains unclear., (© 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.)

This paper studies the resilience‐based output containment control problem of heterogeneous multi‐agent systems in the presence of simultaneous false data injection attacks on both sensors and actuators injected on both cyber and physical layers. In real‐world security problems, malicious adversaries could inject false data injection attacks on both sensors and actuators simultaneously, even with unbounded injections, to maximize their damage to the multi‐agent systems. To address such a problem, a distributed observer is first designed for each follower to estimate the actual system states against unbounded sensor attacks. A resilience‐based control framework is then proposed using state estimation and adaptive control techniques to compensate for the bounded actuator attack signals adaptively. Lyapunov stability analysis shows that uniformly ultimately bounded convergence is achieved despite the simultaneously injected unbounded sensor attacks and bounded actuator attacks on both cyber and physical layers. That is, each follower's output trajectory converges to a small neighbourhood around the convex hull spanned by the leaders' output trajectories. The effectiveness of the proposed theoretical results is verified by case studies using numerical simulations. [ABSTRACT FROM AUTHOR]

Hydroquinone (HQ) is one of the most effective drugs to treat hyperpigmentary disorders, but often causes skin irritation in clinic. Mast cell plays an important role in contact dermatitis and triggering pseudo‐allergic reactions via MRGPRX2. Whether HQ‐induced skin irritant reaction through activating mast cells via MRGPRX2 remains unknown. To investigate the role of mast cells in HQ‐induced skin irritant reaction and verify whether MRGPRX2 participated in the HQ effect on mast cells which contributed to the pathogenesis of skin irritant reaction, a mouse model of HQ‐induced skin irritation was established to observe the local and systemic inflammation associated with mast cell receptor MrgprB2. Human mast cell LAD2 was used to verify the effect of HQ on mast cells via MRGPRX2 by knocking down with siRNA. As a result, mast cells were involved in the development of HQ‐induced irritant reaction, and local inflammation is closely related to mast cell receptor MrgprB2. HQ could activate mast cells via MRGPRX2, causing changes in calcium concentration, degranulation and release of inflammatory cytokines which lead to skin irritant reaction. In conclusion, HQ‐induced skin irritant reaction could be skin pseudo‐allergic reactions achieved by activating mast cells via MRGPRX2. [ABSTRACT FROM AUTHOR]

Aim: Macrophage activation syndrome (MAS), a severe complication of systemic adult‐onset Still's disease (AOSD), has been reported to occur during interleukin‐6 (IL‐6) inhibitor treatment. However, predictors for MAS development are unknown. Therefore, this study investigated predictive features for MAS development after starting IL‐6 inhibitor treatment in systemic AOSD patients. Method: In a single‐center retrospective study involving systemic AOSD patients who were refractory to high‐dose glucocorticoids with immunosuppressants and started IL‐6 inhibitor treatment between April 2008 and March 2020, we compared the baseline clinical features between patients who developed AOSD flare with MAS features (MAS group) and those who did not (non‐MAS group) during IL‐6 inhibitor treatment. Results: Only tocilizumab was used as an IL‐6 inhibitor. Six of 14 refractory systemic AOSD patients developed AOSD flares with MAS features during tocilizumab treatment, including 4 who developed them shortly after initiation. The MAS group had significantly lower neutrophil counts, fibrinogen, and higher IL‐18/C‐reactive protein (CRP) ratio at starting tocilizumab (baseline) than the non‐MAS group. Before starting tocilizumab, neutrophil counts were trending downward and upward in the MAS and non‐MAS groups, respectively, with significant differences in changes. Receiver operating characteristic analysis showed that baseline neutrophil counts and fibrinogen and their changes before tocilizumab treatment and baseline IL‐18/CRP ratio had significant discriminatory abilities for subsequent MAS development. Conclusion: We identified baseline laboratory features associated with MAS development after initiating an IL‐6 inhibitor in refractory systemic AOSD patients. These features may reflect the suppression of IL‐6 signaling, and further suppression of IL‐6 signaling might trigger early‐onset MAS. [ABSTRACT FROM AUTHOR]

The article in Angewandte Chemie discusses the use of ultra-fast magic-angle spinning combined with solid-state NMR to study paramagnetic materials, allowing for the resolution of complex structures and spectra. The research, led by Andrew J. Pell and Guido Pintacuda, demonstrates how this technique can overcome challenges posed by strong hyperfine couplings in these materials. The study highlights the potential of this method in advancing chemistry and materials science research. [Extracted from the article]

Solid‐state NMR experiments on 2H, 31P, 13C, and 1H nuclei, including 31P T1, 1H T1, and 1H T1ρ measurements, as well as on the kinetics of proton‐phosphorus cross‐polarization have been performed to characterize the crystalline and amorphous α‐zirconium phosphates, which were intercalated with D2O and/or CD3OD. The 13C{1H} CP MAS NMR experiment performed for compound 1‐CD3OD (Zr (HPO4)2.0.2CD3OD) with carbon cross‐polarization via protons of phosphate groups has provided a prove that the methanol was intercalated into the interlayer spaces of this compound. The variable‐temperature 2H solid‐echo MAS NMR spectra of intercalated compounds demonstrated that the methanol molecules, in contrast to the mobile water, were immobile, keeping, however, free CD3 rotations around the C3‐axis. It has been demonstrated that the intercalated species, D2O and CD3OD, do not affect the high‐frequency motions of the phosphate groups. By utilizing local structural models that satisfy the constraints of the experimental data, it has been suggested that the immobile methanol molecules are located in the cavity between two neighboring layers of the zirconium phosphates. Thus, the present work illustrates the reliable criteria in a comprehensive NMR approach to structural and dynamic studies of such systems. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study? The physiological function of Mas-related G protein-coupled receptor D (MrgprD) in gastrointestinal motility is unknown. The aim of this study was to assess the effects of MrgprD and its receptor agonists on murine gastrointestinal motility. What is the main finding and its importance? Mrgprd deficiency improved murine gastrointestinal motility in vivo but had no effects on the spontaneous contractions of murine intestinal rings ex vivo. Systemic administration of the MrgprD ligand, either β-alanine or alamandine, delayed gastrointestinal transit in vivo and attenuated the spontaneous contractions of isolated intestinal rings ex vivo., Abstract: Mas-related G protein-coupled receptor D (MrgprD) was first identified in sensory neurons of mouse dorsal root ganglion and has been demonstrated to be involved in sensations of pain and itch. Although expression of MrgprD has recently been found in the gastrointestinal (GI) tract, its physiological role in GI motility is unknown. To address this question, we used Mrgprd knockout (Mrgprd -/- ) mice and MrgprD agonists to examine the effects of Mrgprd gene deletion and MrgprD signalling activation, respectively, on murine intestinal motility, both in vivo and ex vivo. We observed that the deletion of Mrgprd accelerated the transmission of charcoal through the mouse GI tract. But Mrgprd deficiency did not affect the mean amplitudes and frequencies of spontaneous contractions in ileum ex vivo. Colonic motor complexes in the proximal and the distal colon were recorded from wild-type and Mrgprd -/- mice, but their control frequencies were not different. Moreover, in wild-type mice, systemic administration of an MrgprD agonist, either β-alanine or alamandine, delayed GI transit in vivo and suppressed spontaneous contractions in the ileum and colonic motor complexes in the colon ex vivo. Our results suggest that MrgprD and its agonist are involved in the modulation of GI motility in mice., (© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.)

Objectives: To clarify how pediatric rheumatologists treat systemic juvenile idiopathic arthritis (s‐JIA) associated macrophage activation syndrome (MAS) in the real world and to assess the efficacy and safety of dexamethasone palmitate (DEX‐P) in the treatment of s‐JIA‐associated MAS. Methods: This multicenter, retrospective study was conducted at 13 pediatric rheumatology institutes in Japan. This study included 28 patients with s‐JIA‐associated MAS. Clinical findings, such as treatment details and adverse events, were evaluated. Results: Methylprednisolone (mPSL) pulse therapy was selected as the first‐line treatment in more than half of the patients with MAS. Cyclosporine A (CsA) was used as first‐line therapy in combination with corticosteroids in half of the patients with MAS. DEX‐P and/or CsA were selected as the second‐line therapy in 63% of patients with corticosteroid‐resistant MAS. Plasma exchange was selected as the third‐line therapy for DEX‐P and CsA‐resistant MAS. All patients improved and there were no characteristically severe adverse events associated with DEX‐P. Conclusions: The first‐line treatment for MAS in Japan is mPSL pulse therapy and/or CyA. DEX‐P could be an effective and safe therapeutic option for patients with corticosteroid‐resistant MAS. [ABSTRACT FROM AUTHOR]