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In the presence of a chiral spiro phosphoric acid catalyst, the asymmetric reaction of disubstituted ketenes with N–H pyrroles occurred to afford enantioenriched C-acylated pyrroles bearing α-stereogenic carbon centres. The described reaction constitutes a rare example of a catalytic asymmetric reaction of ketenes with carbon-based nucleophiles. [ABSTRACT FROM AUTHOR]

Objective: We aimed to estimate the optimal cut‐off values of liver stiffness measurement (LSM) for diagnosing and staging fibrosis in non‐obese and obese patients with nonalcoholic fatty liver disease (NAFLD). Methods: NAFLD patients diagnosed by liver biopsy according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system were enrolled in this study. Non‐obesity was defined as a body mass index (BMI) less than 25 kg/m2. LSM was performed by experienced physicians within 2 weeks before or after liver biopsy. Results: A total of 158 patients were included. Average BMI of the non‐obese (n = 68) and obese (n = 90) groups was 23.2 ± 1.6 and 27.9 ± 2.5 kg/m2, respectively. After adjusted for age, fibrosis stage, steatosis grade and type 2 diabetes mellitus, the obese group had a LSM of 3.522 kPa higher than the non‐obese patients (P = 0.003). LSM values of the non‐obese patients had a lower trend when stratified by fibrosis stage, especially in cirrhosis (F4; P = 0.021). Applying separate cut‐off values for patients with NAFLD in individual fibrosis stage, 5.8 vs 7.5 kPa (≥ F1), 7.6 vs 8.5 kPa (≥ F2), 9.1 vs 11.2 kPa (≥ F3), and 12.5 vs 14.3 kPa (F4), improved their diagnostic odds ratios compared with overall cut‐off values. In the non‐obese NAFLD group, using a separate cut‐off avoided underestimating 9.1% of patients with cirrhosis. Conclusions: Non‐obese NAFLD group had lower LSM than the obese group. Different cut‐off values should be used to measure liver fibrosis stage in non‐obese and obese NAFLD patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the relationship among inflammatory cytokines including hypersensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6), glycated hemoglobin A1c (HbA1c), and platelet distribution width (PDW) in women with gestational diabetes mellitus (GDM). Methods: Data on 191 pregnant women (96 women with GDM; 95 healthy controls) were extracted from routine prenatal examination records in Nanjing, China. Fasting concentrations of hs-CRP, IL-6, HbA1c, blood cell indices, and glucose at 24–28th gestational weeks were determined. Results: The levels of hs-CRP, IL-6, FPG, PG1h, PG2h, HbA1c, RBC, and PDW significantly were increased (P < 0.05) in GDM group. hs-CRP had a positive correlation with HbA1c and PLT (P < 0.05). The odds ratios of HbA1c and PDW were 7.817 (95% CI 1.921–31.816, P = 0.004) and 1.523 (95% CI 1.158–2.002, P = 0.003), respectively. Furthermore, AUC of the combined diagnosis of GDM including HbA1c, FPG, and PDW reached 0.754, with specificity of 80.0% and sensitivity of 60.4%. Conclusion: Our findings support that elevated levels of hs-CRP, IL-6, HbA1c, and PDW at 24–28th gestational weeks even within the conventional normal range, may be implicated in the pathogenesis of GDM and their evaluation should be part of prenatal care routine. [ABSTRACT FROM AUTHOR]

Highlights: [•] GPx-1 expression dramatically decreased upon the murine ES cell differentiation. [•] Knock-down of GPx-1 resulted in the differentiation of ES cells. [•] Inhibition of GPx-1 activity led to ES cell differentiation. [•] Proteasome mediated the quick degradation of GPx-1. [Copyright &y& Elsevier]

We investigate the statistical distribution for ideal Bose gases with constant particle density in the 3D box of volume V = L 3 . By changing linear size L and imposing different boundary conditions on the system, we present a numerical analysis on the characteristic temperature and condensate fraction and find that a smaller linear size is efficient to increase the characteristic temperature and condensate fraction. Moreover, there is a singularity under the antiperiodic boundary condition. [ABSTRACT FROM AUTHOR]

Background and Purpose: Glial cell‐derived neurotrophic factor (GDNF) maintains gut homeostasis. Dopamine promotes GDNF release in astrocytes. We investigated the regulation by dopamine of colonic GDNF secretion. Experimental Approach: D1 receptor knockout (D1R−/−) mice, adeno‐associated viral 9‐short hairpin RNA carrying D2 receptor (AAV9‐shD2R)‐treated mice, 6‐hydroxydopamine treated (6‐OHDA) rats and primary enteric glial cells (EGCs) culture were used. Incubation fluid from colonic submucosal plexus and longitudinal muscle myenteric plexus were collected for GDNF and ACh measurements. Key Results: D2 receptor‐immunoreactivity (IR), but not D1 receptor‐IR, was observed on EGCs. Both D1 receptor‐IR and D2 receptor‐IR were co‐localized on cholinergic neurons. Low concentrations of dopamine induced colonic GDNF secretion in a concentration‐dependent manner, which was mimicked by the D1 receptor agonist SKF38393, inhibited by TTX and atropine and eliminated in D1R−/− mice. SKF38393‐induced colonic ACh release was absent in D1R−/− mice. High concentrations of dopamine suppressed colonic GDNF secretion, which was mimicked by the D2 receptor agonist quinpirole, and absent in AAV‐shD2R‐treated mice. Quinpirole decreased GDNF secretion by reducing intracellular Ca2+ levels in primary cultured EGCs. Carbachol (ACh analogue) promoted the release of GDNF. Quinpirole inhibited colonic ACh release, which was eliminated in the AAV9‐shD2R‐treated mice. 6‐OHDA treated rats with low ACh and high dopamine content showed decreased GDNF content and increased mucosal permeability in the colon. Conclusion and Implications: Low concentrations of dopamine promote colonic GDNF secretion via D1 receptors on cholinergic neurons, whereas high concentrations of dopamine inhibit GDNF secretion via D2 receptors on EGCs and/or cholinergic neurons. [ABSTRACT FROM AUTHOR]

Eugenol (2-Methoxy-4-(2-Propenyl) Phenol; EUG) is a natural antibacterial ingredient of the essential oil from many aromatic plants. The antimicrobial mechanism of EUG and its combined inactivation effect with pulsed electric fields (PEF) treatment in a hurdle strategy on E. coli ATCC 8739 were investigated. Results showed that membrane integrity and the morphology of E. coli cell were damaged and the membrane permeability was increased when E. coli was exposed to higher levels of EUG. Analysis of fluorescence spectra, molecular docking and atomic force microscope indicated that EUG bound to the AT-rich region of DNA through groove binding mode, leading to morphological alterations and the aggregation of DNA molecules. The combinations of EUG and PEF demonstrated strong synergistic effects for sterilization and it was proven to be an effective method to achieve a higher level of E. coli inactivation. • Eugenol induced an increase in membrane permeability of E. coli cells. • Eugenol destroyed membrane integrity and morphology of E. coli cell. • Eugenol bound to the AT-rich region of DNA of E. coli through groove binding mode. • The binding resulted in morphological alterations and aggregation of DNA molecules. • Combination of eugenol and PEF showed a strong synergistic effect against E. coli. [ABSTRACT FROM AUTHOR]

[Display omitted] • EA pretreatment at HT7 protected myocardial tissue better than EA KI7 in MIRI rats. • EA pretreatment effectively inhibited glutamatergic neurons in FN of MIRI rats. • EA pretreatment inhibited FNGlu to mediate the sympathetic nervous to improve MIRI. Ischemic heart disease is a fatal cardiovascular disease that irreversibly impairs the function of the heart, followed by reperfusion leading to a further increase in infarct size. Clinically, we call it myocardial ischemia–reperfusion injury (MIRI). A growing number of clinical observations and experimental studies have found electroacupuncture (EA) to be effective in alleviating MIRI. This study attempts to investigate whether glutamatergic neurons in fastigial nucleus (FN) of the cerebellum are involved in EA pretreatment to alleviate MIRI via sympathetic nerves, and the potential mechanisms of EA pretreatment process. A MIRI model was established by ligating the coronary artery of the left anterior descending branch of the heart for 30 minutes, followed by 2 hours of reperfusion. Multichannel physiological recordings, electrocardiogram, cardiac ultrasound, chemical genetics, enzyme-linked immunosorbent assay and immunofluorescence staining methods were combined to demonstrate that EA pretreatment inhibited neuronal firing and c-Fos expression in FN of the cerebellum and reduced cardiac sympathetic firing. Meanwhile, EA pretreatment significantly reduced cardiac ejection fraction (EF), shortening fraction (SF), percentage infarct area, decreased myocardial norepinephrine (NE), creatine kinase isoenzyme MB (CK-MB) concentrations, and improved MIRI-induced myocardial tissue morphology. The results were similar to the inhibition of glutamatergic neurons in FN. However, the activation of glutamatergic neurons in FN diminished the aforementioned effects of EA pretreatment. This study revealed that glutamatergic neurons in FN of the cerebellum is involved in EA pretreatment mediated sympathetic nervous and may be a potential mediator for improving MIRI. [ABSTRACT FROM AUTHOR]

Eugenol (EUG; 4‐allyl‐2‐methoxyphenol) is a natural antibacterial component from essential oil. The effects of EUG on cell membrane fatty acid composition, membrane fluidity and resistance to pulsed electric field (PEF) of Escherichia coli ATCC 8,739 (E. coli) were investigated. Results indicated that the PEF resistance of E. coli decreased as EUG concentration increased, which may be related to the alterations in membrane fatty acid composition and fluidity. Gas chromatography−mass spectrometry and micro‐Raman spectroscopy showed that EUG increased membrane fluidity by notably increasing the proportion of unsaturation fatty acids and simultaneously decreasing the content of cyclic fatty acids. These results revealed that PEF resistance of E. coli was influenced by EUG due to alterations of fatty acid composition and membrane fluidity. Practical applications: Pulsed electric field (PEF), as a widely used non‐thermal sterilization technology, has gained much attention and increasingly focused on improving the efficiency to inactivate micro‐organisms. Eugenol (EUG; 4‐allyl‐2‐methoxyphenol) derived from cloves is a natural phenol essential oil and exhibits several pharmacological properties such as being an antimicrobial. Our results revealed the underlying mechanism that EUG reduced PEF resistance of E. coli cells and contributed to achieve better understanding of microbial inactivation by PEF. Therefore, a new route for the application of eugenol to improve the efficiency of PEF in the food industry was created. [ABSTRACT FROM AUTHOR]

Relativistic multichannel theory has been used to calculate the even-parity Rydberg states and odd-parity autoionizing (AI) Rydberg spectrum converging to the limit of second and third excited core states of selenium (Se), taking into account the ionic core dipole polarization effect caused by the Rydberg electron. Six even-parity Rydberg series 4 s 2 4 p 3 ( ​ 4 S o ) n p 3 P 0 , 1 , 2 and 4 s 2 4 p 3 ( ​ 4 S o ) n p 5 P 1 , 2 , 3 are calculated, along with AI Rydberg states converging to 4 s 2 4 p 3 ( ​ 2 D 3 / 2 o ) or 4 s 2 4 p 3 ( ​ 2 D 5 / 2 o ) in J π = (1) − , (2) − or (3) − symmetry. In general, there is less than a 0.05 difference between calculated and experimental quantum defects. The influence of the perturbers on quantum defects and peak profiles has all been investigated. The accuracy of our calculations allows us to provide a reliable the assignment of the measured AI Rydberg states and the accompanying total angular momentum. [ABSTRACT FROM AUTHOR]

Objectives: In this study we aimed to assess the clinicopathological characteristics and long‐term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) having distinct steatosis distribution patterns. Methods: Clinicopathological data of 238 individuals with biopsy‐confirmed NAFLD were collected. Nonalcoholic steatohepatitis‐clinical research network (NASH‐CRN) and steatosis, activity and fibrosis (SAF)/fatty liver inhibition of progression (FLIP) algorithm were used. Cumulative incidence of liver‐related events (LREs) was compared by Kaplan–Meier analysis. Univariate and multivariate logistic regression analyses were used to identify independent predictors for steatosis distribution. Results: Eligible patients were categorized into three groups based on their steatosis distribution, including azonal steatosis (AS) (62 [26.1%]), perivenular steatosis (PVS) (147 [61.8%]), and the pan‐acinar steatosis (PAS) groups (29 [12.1%]). There were significantly higher ballooning grade and disease activity (P < 0.05), more severe fibrosis (P < 0.001), and a higher cumulative incidence of LREs (hazard ratio [HR] 8.0, 95% confidence interval [CI] 2.34–27.35, P < 0.0001) in the AS group than in the PVS and PAS groups after a median of 3.6‐year follow‐up. Multivariate logistic regression analysis revealed age (odds ratio [OR] 1.11, 95% CI 1.06–1.16, P < 0.001) might be independently associated with AS distribution, and PNPLA3 rs738409 CG/GG genotype (OR 3.36, 95% CI 0.98–11.47, P = 0.053) might also play a role. Conclusions: AS is associated with more severe disease activity and fibrosis stage in NAFLD, and predisposes toward poor prognosis. Age might be an independent predictor for AS in NAFLD, while PNPLA3 rs738409 CG/GG genotype might also play a role. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent joint inflammation. The development of rheumatoid arthritis is directly correlated with the disturbance of gut microbiome and its metabolites. RA can be effectively treated with the Danggui Sini decoction (DSD), a Traditional Chinese medicine (TCM) prescription from the Treatise on Febrile Diseases. Further research is needed to clarify the precise mechanism of DSD in the treatment of RA. In this study, 1H NMR metabonomics and 16 S rRNA gene sequencing techniques were used to clarify the intervention of DSD on CIA-induced RA. The results of 1H NMR metabolomics of feces revealed that five metabolites (alanine, glucose, taurine, betaine, and xylose) were disturbed, which could be regarded as potential biomarkers of RA. The intestinal microbiome of RA rats had changed, according to the results of 16 S rRNA gene sequencing; eight microbes (g_norank_f_Eubacterium_coprostanoligenes_group , g_Ruminococcus_torques_group , g_Dubosiell , g_Lactobacillus , g_norank_f_Desulfovibrionaceae , g_Bacteroides , g_Oscillibacter , and g_Romboutsia) occurred significantly at the genus level, and DSD significantly impacted six of them (g_Dubosiell , g_Lactobacillus , g_norank_f_Eubacterium_coprostanoligenes_group , g_Ruminococcus_torques_grou , g_Bacteroides , and g_Romboutsia). Three of them (g_norank_f_Eubacterium_ coprostanoligenes_group , g_Romboutsia , and g_Lactobacillus) were regarded as key microbiomes for DSD to treat RA, and three common metabolic pathways (taurine and hypotaurine metabolism; alanine, aspartate, and glutamate metabolism; primary bile acid biosynthesis) were discovered based on the 1H NMR metabonomics and PICRUST2 prediction of 16 S rRNA gene sequencing. Six SCFAs in feces (acetic acid, butyric acid, propionic acid, caproic acid, isobutyric acid, and valeric acid) increased significantly in RA, according to the outcomes of targeting SCFAs, while five SCFAs (acetic acid, butyric acid, propionic acid, caproic acid, and valeric acid) had decreased significantly due to DSD treatment. In conclusion, our study indicated that DSD could regulate RA's metabolic disorder by affecting intestinal microbiome and its metabolites. It also establishes a framework for future research into exploiting gut microbes therapeutic to treat RA. • Combining metabolomics and 16 Sr RNA gene sequencing to reveal the therapeutic mechanism of DSD in the RA with Cold Bi syndrome. • Five metabolites were considered as potential biomarkers concerning collagen-induced rheumatoid arthritis. • Six intestinal bacteria were considered to be the key bacteria for DSD treating RA. • Three key pathways are considered for DSD treating RA by combined analysis of metabolomics and 16 S rRNA Gene Sequencing [ABSTRACT FROM AUTHOR]

Abstract: Fe x Co y Ni100−x−y alloy nanoparticles with controllable compositions attached on the surface of carbon nanotubes (CNTs) were synthesized using an easy two-step route including adsorption and reduction processes. The nanocomposites have been characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED), energy-disperse X-ray spectroscopy (EDS) and vibrating sample magnetometer (VSM). The effect of the alloy composition on microstructure and magnetic properties of ternary FeCoNi alloys attached on carbon nanotubes have been studied. During the nominal composition range (x =21, 24, 33, 37, 46 and y =60, 46, 48, 48, 35), Fe x Co y Ni100−x−y alloy nanoparticles attached on CNTs are quasi-spherical, fcc–bcc dual phase, and the coercivity (H c) and saturation magnetization (M s) vary with the alloy composition. The H c of Fe x Co y Ni100−x−y alloy nanoparticles attached on CNTs decreases and M s increases with increasing Fe content. These demonstrate that the two-step route is promising for fabricating alloy nanoparticles attached on CNTs for magnetic storage and ultra high-density magnetic recording applications. [Copyright &y& Elsevier]

Summary Many infections and stress signals can rapidly activate the NLRP3 inflammasome to elicit robust inflammatory responses. This activation requires a priming step, which is thought to be mainly for upregulating NLRP3 transcription. However, recent studies report that the NLRP3 inflammasome can be activated independently of transcription, suggesting that the priming process has unknown essential regulatory steps. Here, we report that JNK1-mediated NLRP3 phosphorylation at S194 is a critical priming event and is essential for NLRP3 inflammasome activation. We show that NLRP3 inflammasome activation is disrupted in NLRP3-S194A knockin mice. JNK1-mediated NLRP3 S194 phosphorylation is critical for NLRP3 deubiquitination and facilitates its self-association and the subsequent inflammasome assembly. Importantly, we demonstrate that blocking S194 phosphorylation prevents NLRP3 inflammasome activation in cryopyrin-associated periodic syndromes (CAPS). Thus, our study reveals a key priming molecular event that is a prerequisite for NLRP3 inflammasome activation. Inhibiting NLRP3 phosphorylation could be an effective treatment for NLRP3-related diseases. [ABSTRACT FROM AUTHOR]