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Procollagen protein was lower in UVB-irradiated and UVB + etanercept-treated mice. TNFα blockade decreased decorin and TGF-β1 in UVB-irradiated mice compared to UVB alone. MMP13 was inhibited by etanercept in UVB-irradiated mice (p less then 0.01). In conclusion, blockade of TNFα significantly decreased mature collagen in UVB-irradiated mice, while increasing collagen fragmentation and decreasing procollagen.The unreasonable use of antibiotics in poultry breeding has led to the frequent occurrence of antibiotic residues in poultry products, affecting food safety and posing a threat to human health. Accurate and rapid detection of antibiotic drug content is therefore of great significance. In this study, a new metamaterial method based on terahertz (THz) spectroscopy for the detection of the quinolone antibacterial drug noroxin in low concentrations was developed and tested. First, a new metamaterial structure was designed using a computational electromagnetics simulation tool with experimental verification. Three-dimensional full-wave electromagnetic field simulations and measured transmission spectra for the metamaterials were observed. Second, the transmission spectra of photoresists with different thicknesses (0-40 µm) on the metamaterials surface were simulated, and the transmission spectra of noroxin thin films of different concentrations on the metamaterial surface were measured. Finally, using a purchased standard sample of noroxin in ethanol (100 µg/mL) as the mother liquor, test samples of different concentrations were prepared, and experiments and multivariate data analysis were carried out. The noroxin detection limit for the method presented in this paper was determined as 0.01 µg/mL. Thus, the new metamaterial method based on terahertz spectroscopy designed in this study was shown to effectively detect low concentrations of noroxin, providing a theoretical and experimental basis for the rapid detection of quinolone antibiotic residues in food matrices.The use of peptidomics to find diagnostic markers has attracted increasing clinical attention. Ulcerative colitis (UC) is a type of inflammatory bowel disease, and the traditional auxiliary diagnostic technique is colonoscopy. However, this invasive method is not effective in distinguishing between patients with endoscopic remission and healthy people, which carries the risk of delayed diagnosis of UC. In this study, we used peptidomics to find serum diagnostic markers for different stages of UC. A total of 78 serum samples were collected to form a training set (60 samples) and a testing set (18 samples). Among them, patients with active UC, remitting UC and healthy people accounted for one third each. The nano-liquid chromatography coupled with hybrid linear trap quadrupole orbitrap mass spectrometry was used for detection of low molecular weight peptides in serum. According to the protein database search and de novo sequencing algorithm, forty peptides were simultaneously identified in all samples. Six biomarker peptides were screened in the training set through orthogonal partial least-squares-discriminant analysis and receiver operating characteristic curve analysis. These six peptides were derived from proteins involved in coagulation and complement activation. We evaluated the diagnostic ability of the six peptides in the testing set through hierarchical cluster analysis, and showed that perturbation of these peptides could distinguish patients with active UC, patients with remitting UC and healthy people. This study validated the feasibility of serum peptidomics for the discovery of diagnostic markers, and provided a potential method for diagnosing different stages of UC.Ligustri Lucidi Fructus (LLF) is a traditional Chinese medicine to treat osteopathic and hepatic diseases. Wine steaming is the major processing method for LLF in Chinese Pharmacopoeia, but the chemical changes involved are still unclear. In this study, a research strategy was proposed to reveal the chemical changes during wine steaming processing of LLF. Firstly, in total 104 compounds were tentatively identified using UHPLC/Orbitrap-MS. Secondly, potential chemical changes were revealed by comparing the peak areas of the 104 compounds between LLF and the corresponding wine-steamed LLF (WLLF). The results indicated that iridoid and phenylethanoid esters were readily hydrolyzed during wine steaming processing, while organic acids, flavonoids, and triterpenes were stable. Finally, 7 selected compounds were simultaneously determined in 21 batches of LLF/WLLF samples using a 10-min UPLC/UV method. The contents of 4 esters decreased from 3.64% to 2.71%, and the contents of 3 potential hydrolysis products increased from 0.27% to 0.88% after processing. Our study indicated that hydrolysis of iridoid and phenylethanoid esters such as specneuzhenide was responsible for the chemical changes during the wine processing of LLF. The proposed strategy could be employed to investigate the chemical changes of other herbs during processing.BMS-986142 has been developed as an innovative Bruton's tyrosine kinase inhibitor for treatment of several autoimmune diseases. The drug substance of BMS-986142 may contain three potential atropisomeric impurities due to its unique structural characteristics. Developing a single liquid chromatography (LC) method to separate all four highly structurally related atropisomers and other process impurities from each other turned out to be a daunting task. Two-dimensional LC (2DLC) was found to be an extremely powerful enabling technology for extracting purity information out of the complex sample impurity profile and facilitated process development before a final single dimension method was discovered. The off-the-shelf 2DLC instrument could be configured to allow injection of the targeted first dimension peak through either no-loss multiple heart-cutting fractions or as a large, single volume fraction with on-line dilution. Excellent precision (relative standard deviation of 0.3 %) and recovery (101.2 ± 0.2 %) was achieved for an atropisomer impurity at a 10 % monitoring level in the first configuration with sensitivity down to 0.2 % w/w. With the second instrument configuration, which eliminated the need for fraction recombination, similar figures of merit were maintained for the second dimension at the cost of losing the ability to collect and park multiple fractions.
To evaluate psychosocial long-term outcome in patients diagnosed with psychogenic nonepileptic seizures (PNES) and to predict outcome of PNES, economic status, and quality of life (QoL) at follow-up.

Patients diagnosed with PNES in the video-EEG-monitoring unit at our Epilepsy center between 2002-2016 were contacted by phone 1-16 years after communicating the diagnosis. Patients underwent a structured interview asking for current PNES status, psychosocial situation (economic status, marital status, setting of living, driving), depression, and QoL.

Of 70 PNES patients without comorbid epilepsy (age 41.1 ± 13.5 years; 74 % female, follow-up 5.2 ± 4.2 years), 23 patients (33 %) reported to be free of PNES during the last 12 months. Patients with cessation of PNES were younger at PNES onset (p < .01) and diagnosis (p < .01) and had a higher education (p < .05). At follow-up, the proportion of economically active patients only increased in individuals with cessation of PNES (p < .001) while an increased number of patients with persisting PNES relied on governmental support (p < .001). Cessation of PNES was associated with better mood (p < .01) and QoL (p < .001). In multiple regression models, cessation of PNES was only predicted by younger age at onset, while good economic outcome was determined by younger age and good economic status at diagnosis and cessation of PNES at follow-up. Good QoL at follow-up was predicted by low depressive symptoms, freedom of PNES, and economic activity at follow-up.

Long-term outcome in patients with PNES remains to be poor and the majority of patients continue to have PNES. Cessation of PNES was associated with good economic outcome, mood, and QoL.
Long-term outcome in patients with PNES remains to be poor and the majority of patients continue to have PNES. Cessation of PNES was associated with good economic outcome, mood, and QoL.Underutilization of community care services has been described for informal dementia caregivers. Most research has however examined caregivers' access to home or respite care rather than to services for themselves. selleck kinase inhibitor The aims of this study are to describe access and retention of informal dementia caregivers in psychosocial interventions; examine the perceived effects of interventions among users and motives for non-use among non-users; and compare caregivers with and without lifetime access and retention in psychosocial interventions across predisposing, enabling and need variables. A cross-sectional study was conducted with 179 Portuguese caregivers, who replied to a web-based survey. Participants were fairly distributed among those who have never (49.7%) and those who have ever accessed (50.3%) psychosocial interventions. Individual psychological support was the most used intervention (32.2%). Caregivers' age, time elapsed since diagnosis and the relationship with the care receiver were associated with lifetime access to various intervention types. Dropout was above 50% for most intervention types, except for psychoeducation (31.8%). Associations were found between a history of dropout/retention and caregivers' education, perceived mental health, and the number of hours spent caring. Most users of psychoeducational interventions (>80%) appraised it as beneficial to learn about the disease, provide quality care and cope with caregiving. Informational barriers were the most reported by non-users of psychoeducational interventions (45.1%). The findings show that dementia caregivers continue facing barriers to use and keep using community services for themselves. The influence of particular predisposing and need variables on access to psychosocial interventions can vary according to intervention types.The oxysterol-binding protein-related proteins (ORPs) have emerged as orchestrators of phosphatidylinositol-4,5-bisphosphate (PIP2) and cholesterol trafficking to the plasma membrane (PM). In this scenario, recent studies raised the prospect of ORPs cooperative behavior in sustaining leukemia stem cells (LSCs) survival by remotely enhancing ER-mitochondria Ca2+ communication. At the apex of the signaling cascade, the aberrantly upregulated LSC-ORP4L fosters PM-PIP2 extraction & cleavage, endoplasmic reticulum (ER)-Ca2+ release and mitochondrial energetics. The theoretical ember of draining fuel from the chemoresistant LSCs by restraining endoplasmic reticulum (ER)-mitochondria Ca2+ fluxes in a lipid-contingent fashion ensues. In light of relevant literature, this review briefly and critically discusses some key molecular ins & outs underlying such therapeutic opportunity in acute myeloid leukemia (AML).During the last two decades, numerous observed data obtained by various physical techniques, also supported by molecular modeling approaches, have highlighted the structuring features of tripeptides, as well as their aggregation properties. Herein, we focus on the structural dynamics of four trimers, i.e., Gly-Gly-Gly, Gly-Ala-Gly, Ala-Ala-Ala and Ala-Phe-Ala, in an aqueous environment. Density functional theory calculations (DFT) were carried out to assess the stability of four types of secondary structures, i.e., β-strand, polyproline-II (pP-II), α-helix and γ-turn, of which the formation had been described in these tripeptides. Both implicit and explicit hydration effects were analyzed on the conformational and energetic features of trimers. It has been shown that the use of M062X functional (versus B3LYP) improve the stability of intramolecular H-bonds, especially in inverse γ-turn structures, as well as the energetic and conformational equilibrium in all tripeptides. Explicit hydration reflected by the presence of five water molecules around the backbone polar sites (NH3+, N-H, CO and NH2) considerably changes the conformational landscapes of the trimers.
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