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Background: Endotheliopathy is a common pathologic finding in patients with acute and long COVID-19. It may be associated with disease severity and predispose patients to long-term complications. Plasma levels of a proteoglycan, syndecan-1, are found to be significantly elevated in patients with COVID-19, but its roles in assessing disease severity and predicting long-term outcome are not fully understood. Methods: A total of 124 consecutive hospitalized patients with SARS-CoV-2 infection were prospectively enrolled and blood samples were collected on admission (T1), 3–4 days following treatment (T2), and 1–2 days prior to discharge or death (T3). Plasma levels of syndecan-1 were determined using an immunosorbent assay; various statistical analyses were performed to determine the association between plasma syndecan-1 levels and disease severity or the 60-day mortality rate. Results: Compared with those in the healthy controls, plasma levels of syndecan-1 in patients with critical COVID-19 were significantly higher (p < 0.0001). However, there was no statistically significant difference among patients with different disease severity (p > 0.05), resulting from large individual variability. Longitudinal analysis demonstrated that while the levels fluctuated during hospitalization in all patients, plasma syndecan-1 levels were persistently elevated from baseline in critical COVID-19 patients. Cox proportional hazard regression analyses revealed that elevated plasma levels of syndecan-1 (>260 ng/mL at T1, >1018 ng/mL at T2, and >461 ng/mL at T3) were significantly associated with the 60-day mortality rate. Conclusions: Endotheliopathy, marked by glycocalyx degradation and elevated plasma syndecan-1, occurs in nearly all hospitalized patients with SARS-CoV-2 infection; elevated plasma syndecan-1 is associated with increased mortality in COVID-19 patients. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the major anthocyanins of blueberry extracts from northeast China and explore their vision health improvement effects. HPLC-Q-TOF-MS/MS results suggested that six different anthocyanins were accurately identified, among which the Cy-3-glu (C3G) was the most abundant, ranging from 376.91 ± 7.91 to 763.70 ± 4.99 μM. The blueberry extract contained a higher purity of anthocyanins, and the anthocyanosides reached 342.98 mg/kg. The anti-oxidative stress function of C3G on HG-treated ARPE-19 cells were evaluated, and showed that the GSSG level of HG-cells pretreated with 10 μM C3G was significantly decreased, while the Nrf2 and NQO1 gene expression levels were increased. Further molecular docking (MD) results indicated that the C3G displayed favorable binding affinity towards REDD1, and only the B-ring of the C3G molecule displayed binding interactions with the CYS-140 amino acids within the REDD1 protein. It implied that the oxidative stress amelioration effects of C3G on the ARPE-19 cells were related to the REDD1 protein, which was probably via the Nrf2 pathways, although further studies are needed to provide mechanism evidence. The present study provides novel insights into understanding the roles of blueberry anthocyanins in ameliorating oxidative stress-induced BRB damage in the retina. [ABSTRACT FROM AUTHOR]

• Highly transparent and nearly superhydrophobic surface can be achieved. • The relationship between optical transmittance and etching depth was studied. • Surface roughness-dependent water contact angle and sliding angle were studied. Highly transparent, superhydrophobic coatings are highly desirable for maintaining long-lasting clarity for outdoor camera windows. In this study, the authors present a simple approach to create a wide–range anti-reflective and highly hydrophobic layer on a glass surface. This is accomplished through a hydrothermal alkali etching process combined with a dip-coating process using 1 H, 1 H, 2 H, 2 H-Perfluorooctyltrimethoxysilane (POTS). The sample, etched for 20 h and modified by POTS, exhibiting an average transmittance of 96.5 %, a water contact angle (WCA) of 140° and a sliding angle (SA) of 40°. The results of the water spray experiment indicate this surface exhibits excellent water repellent performance, preventing water droplets larger than 0.01 mm in size. The relationship between optical transmittance and etching depth was thoroughly studied, revealing that an etched depth ranging from 200 nm to 600 nm yields optimal wide-spectrum anti-reflective properties. Furthermore, the influence of surface roughness on apparent WCA and SA was investigated. It was found that root mean square (RMS) roughness can be an effective factor to predict the apparent WCA of a surface, while both the RMS roughness and morphological structure affect the SA. [ABSTRACT FROM AUTHOR]

Kratom is an herbal supplement which is used for its stimulating properties and pain reduction due to interaction with opioid receptors. Kratom overdose may cause fatality. A 56-year-old man was admitted to the emergency department with severe jaundice and liver failure. His total bilirubin reached at 70.6 mg/dL, but extensive workup did not show any liver mass. Family informed that the patient was taking Kratom. Plasma exchange was suggested as an unconventional therapy and consent from the patient was obtained because this procedure has never been performed to treat Kratom toxicity before. After four procedures, his total bilirubin was reduced to 23.9 mg/dL and his clinical condition improved significantly. Finally on day 5 he was discharged at stable condition with a total bilirubin value of 21.3 mg/dL. There is no antidote for Kratom, and treatment is supportive. To our knowledge this is the first report of reversing Kratom poisoning using plasma exchange. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cell therapy is an immunotherapy that has resulted in tremendous progress in the treatment of patients with B cell malignancies. However, significant toxicities may also be associated with such therapy. Here we report extremely high ferritin in a male patient after such therapy. We present a case of a 52 year old male with a history of B-cell acute lymphoblastic leukemia who received chimeric antigen receptor T-cell (CAR-T) therapy with rapcabtagene autoleucel (carvykti). The patient subsequently developed cytokine release syndrome (CRS) which during its resolution results in a hemophagocytic lymphohistiocytosis (HLH)-like syndrome that fell short of being diagnostic. This syndrome tracked closely with the onset and resolution of immune-effector cell-associated neurotoxicity syndrome (ICANS), with close correlation between the severity of laboratory abnormalities, particularly extremely high ferritin (peak value: 81,540 μg/L), and clinical encephalopathy. Cytokine release syndrome after experimental (CAR) T cell therapy may cause extremely elevated ferritin and hemophagocytic lymphohistiocytosis −like syndrome. [ABSTRACT FROM AUTHOR]

BACKGROUND The palm oil (PO), leaf lard oil (LO), rapeseed oil (RO), sunflower oil (SO) and linseed oil (LN) are five of the most typical dietary lipids in most Asian countries. However, their influences on gut health, and the connections between the fatty acid composition, the gut microbiota, and the bile acid metabolism are not fully understood. RESULTS: In the present study, results showed that compared with polyunsaturated fatty acid (PUFA)‐rich SO and LN, the saturated fatty acid (SFA)‐rich and monounsaturated fatty acid (MUFA)‐rich PO, LO and RO were more likely to decrease the re‐absorption of bile acid in the colon, which was probably caused by their different role in modulating the gut microbiota structure. LO consumption significantly up‐regulated the Cyp27a1, FXR and TGR5 gene expression level (P < 0.05). The correlation results suggested that the C18:0 was significantly positive correlated with these three genes, indicating that intake of SFA‐rich dietary lipids, especially for the C18:0, could specifically increase the bile acid production by stimulating the bile acid alternative synthesis pathway. Although the bile acid receptor expression in the colon was increased, the re‐absorption of bile acid did not show a significant increase (P > 0.05) as compared with other dietary lipids. Moreover, the C18:2‐rich SO maintained the bile acid metabolic balance probably by decreasing the Romboutsia, while increasing the Bifidobacterium abundance in the colon. CONCLUSIONS: The different dietary lipids showed different effects on the bile acid metabolism, which was probably connected with the alterations in the gut microbiota structure. The present study could provide basic understandings about the influences of the different dietary lipids consumption on gut homeostasis and bile acid metabolism. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The development of insect appendages requires the expression of multiple genes in a strict spatial and temporal order. The odd‐skipped family genes are vital transcriptional factors involved in embryonic development. The development and morphogenesis of the insect wing requires multiple transcription factors to regulate the expression of wing patterning genes at the transcriptional level. However, the function of odd‐related genes in insect wing morphogenesis and development during postembryonic stages is unclear. We focused on the roles of the sister of odd and bowl (sob) gene, a member of odd‐skipped family genes, during the wing morphopoiesis in Bombyx mori using the clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR‐associated protein 9 system and in Tribolium castaneum by RNA interference. The results showed that the wings were significantly smaller and degenerated, and wing veins were indistinct in the sob gene loss‐of‐function group in both B. mori and T. castaneum. Quantitative real‐time polymerase chain reaction revealed that the Tcsob gene regulated the expression of wing development genes, such as the cht 7 and the vg gene. The findings suggest the importance of sob gene in insect wing morphology formation during postembryonic stages. [ABSTRACT FROM AUTHOR]

The processing of dietary lipids in the intestinal lumen involves metabolic processes of the host and also of the microbial organisms that reside in the gut. Whereas, in the edible oil, there are also other minor content of components, such as fat-soluble micronutrients. The dietary oils and fats, as well as these accompanied components have different effects on the gut microbiota structure, which is also closely associated with gut inflammation, and the host health. This review of the literature highlights the effects of dietary oils and fats, as well as the minor content of accompanied components on the gut microbiota, and the gut inflammation, with special respect to illustrating the roles of high fat diet (HFD), fatty acid composition, the n6/n3 poly-unsaturated fatty acid (PUFA) ratio, the conjugated linoleic acids (CLAs), the fatty acid chain length and triacylglycerol (TAG) structure, the fat-soluble micronutrients, and some other minor content of components, such as trans -fatty acids (TFAs). The interactions between the dietary oils and fats and gut microbiota are also briefly discussed. The diversity in dietary oils and fats composition affects the gut microbiota structure, and the unhealthy dietary lipid pattern, such as HFD or diet rich in saturated fats may lead to the gut microbiota dysbiosis not only by decreasing their richness and diversity, but also by changing the Firmicutes to Bacteroidetes ratio, further raising the intestinal pro-inflammatory cytokines levels and permeability of the intestine mucosa. The balanced dietary oils and fats intake is recommended to achieve the appropriate fatty acid consumption ratio, especially for the n6/n3 PUFA ratio, thereafter, maintaining both of the gut microbiota homeostasis and host health. The accompanied minor content of fat-soluble bioactive components also showed positive roles for the overall gut health. However, more clinic evidence should be provided in future studies. [Display omitted] • Influences of dietary oils and fats composition on the gut microbiota and gut inflammation were elaborated. • The roles of the accompanied minor components in dietary oils and fats on gut homeostasis were reported. • Interactions between dietary oils and fats, and gut microbiota in the intestinal inflammation regulation were discussed. [ABSTRACT FROM AUTHOR]

Dysregulated lysophosphatidic acid receptor 1 (LPAR1) signaling is implicated in fibrotic diseases, including systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Fipaxalparant (HZN‐825) is a small molecule acting as a negative allosteric modulator of LPAR1 and is in phase 2 clinical evaluations for treating diffuse cutaneous SSc and IPF. This open‐label, phase 1 study examined the pharmacokinetics (PKs), food effect, and safety of fipaxalparant in healthy volunteers. Dose proportionality was evaluated for fipaxalparant single doses of 150, 300, and 450 mg under fasted conditions. Food effect was tested with a 450‐mg single dose under fasted conditions or with a high‐fat meal. Multiple‐dose PKs for twice‐daily dosing of either 300 or 450 mg with low‐ or high‐fat meals was also assessed. Fipaxalparant was safe and well tolerated in healthy volunteers (n = 36) under all conditions. Fipaxalparant exposure increased in a less than dose‐proportional manner from 150 to 450 mg. At 450 mg, a high‐fat meal increased the maximum observed concentration and area under the curve by approximately 1.9‐ and 2.1‐fold, respectively. These results, combined with prior preclinical and phase 2a data, informed dose selection of fipaxalparant 300 mg once and twice daily with a meal for phase 2b studies. [ABSTRACT FROM AUTHOR]

Background: Daratumumab (DARA) is a human monoclonal antibody for the treatment of multiple myeloma (MM). DARA binds to CD38 on RBCs and interferes with detection of RBC alloantibodies. The objective of this study was to evaluate the risk of RBC alloimmunization in MM patients treated with DARA. Materials and methods: A retrospective study of the complete serological profile and transfusion history of 45 MM patients received transfusion and treated with DARA from July 2015 to December 2018 was undertaken. All cases with positive Ab screens were treated with DTT to identify RBC alloantibodies. RBC transfusion history was monitored between the first DARA dose to the last or extending to the first negative Ab screen after the last DARA dose if the Ab screen was ever positive. Forty‐six MM patients received transfusion but not DARA were studied as control group. Results: Totally 184 Ab screens were done on 45 patients transfused with ABO‐Rh compatible RBCs, phenotypically matched units or both. None of them showed detectable alloantibodies after DTT treatment. The duration of Ab screening positivity varied markedly, ranging from 25 days to 5 months after the last dose. Two of 46 patients in the control group had preexisting alloantibodies but no new alloantibodies were detected during study period. Conclusions: Our results indicate that the risk of forming new RBC alloantibodies after transfusion in MM patients treated with current regimens is very low and no DARA‐associated difference in the alloimmunization risk. No significant difference in alloimmunization is detected between ABO‐Rh compatible and phenotypically matched transfusion. [ABSTRACT FROM AUTHOR]

Osteoporosis, a skeletal ailment marked by bone metabolism imbalance and disruption of bone microarchitecture, Neferine, a bisbenzylisoquinoline alkaloid with diverse pharmacological activities, has received limited attention in the context of osteoporosis treatment. We employed a bilateral ovariectomy (OVX) rat model to induce osteoporosis and subsequently administered Neferine treatment for four weeks following successful model establishment. Throughout the modeling and treatment phases, we closely monitored rat body weights. We assessed alterations in bone tissue microstructure through micro-CT, HE staining, and safranin O-fast green staining. Levels of bone formation and resorption markers in serum were evaluated using ELISA assay. Western blot analysis was employed to determine the expression levels of p38MAPK, p-p38MAPK, and bone formation-related genes in bone tissue. We isolated and cultured OVX rat BMSCs (OVX-BMSCs) and induced osteogenic differentiation while simultaneously introducing Neferine and the p38MAPK inhibitor SB203580 for intervention. Neferine treatment effectively curbed the rapid weight gain in OVX rats, ameliorated bone loss, and decreased serum levels of TRAP, CTX-I, PINP, and BALP. Most notably, Neferine promoted the expression of bone formation-related factors in bone tissue of OVX rats, while concurrently activating the p38MAPK signaling pathway. In in vitro experiments, Neferine facilitated the expression of bone formation-related factors in OVX-BMSCs, increased the osteogenic differentiation potential of OVX-BMSCs, and activated the p38MAPK signaling pathway. Nevertheless, SB203580 partially reversed Neferine's promotive effect. Neferine can boost the osteoblastic differentiation of BMSCs and alleviate OVX-induced osteoporosis in rats by activating the p38MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Fatty acid species and locations within TAGs affect lipid digestion rate and extent. • Maximum FFA release extent upon pancreatic lipase reaction: PO > RO > LINO > SO > LO. • Apparent FFA release constants were PO > SO ≈ RO > LO ≈ LINO during in-vitro digestion. • Short-chain saturated fatty acids released faster than long-chain poly-unsaturated fatty acids. • Correlations were found between lipid compositions, lipid digestion and serum fatty acids profiles. Abstract The objective of the present study was to investigate the influences of dietary lipid composition on the gastrointestinal digestion and postprandial serum lipid profiles, and the connections between them. The in-vitro digestion results showed that maximum free fatty acid (FFA) release level of different lipid samples was PO (Palm oil) > RO (Rapeseed oil) > LINO (Linseed oil) > SO (Sunflower oil) > LO (Lard oil), and the first-order kinetics apparent rate constant was PO > SO ≈ RO > LO ≈ LINO, this may probably be ascribed to their specific lipid fatty acid composition and TAG structure. The individual FFA released during 240 min in-vitro digestion time was measured, and it showed that the release rate of short-chain saturated fatty acids (e.g. C16:0 in PO) were higher than the long-chain poly-unsaturated fatty acids (e.g. C18:3n-3 in LINO). Besides, the position of fatty acids within TAG molecules could also impose influences on the lipid hydrolysis process upon pancreas lipase in gastrointestinal tract using in-vitro digestion model. The postprandial serum fatty acid composition of the adult SD male rats were examined within 240 min after oral gavage administration, and the Pearson correlations between lipid fatty acid composition and the serum fatty acid profiles were analyzed. Certain correlations were summarized between lipid compositions (i.e. fatty acid composition and TAG structure), lipid digestion fates and serum fatty acid content in postprandial. The present work may provide some basic understandings of the connections among lipid compositions, lipid gastrointestinal digestion differences and the postprandial serum lipid profiles, and provide useful information about their nutritional and functional evaluation. [ABSTRACT FROM AUTHOR]

Background: Intestinal barrier dysfunction is a significant clinical problem, commonly developing in a variety of acute or chronic pathological conditions. Herein, we evaluate the effect of microRNA-31 (miR-31) on intestinal barrier dysfunction through NF-κB/HIF-1α pathway by targeting HMOX1 in rats with sepsis. Methods: Male Sprague-Dawley rats were collected and divided into the sham group, and the cecum ligation and perforation group which was subdivided after CACO-2 cell transfection of different mimic, inhibitor, or siRNA. Levels of serum D-lactic acid, diamine oxidase and fluorescence isothiocyanate dextran, FITC-DX concentration, and bacterial translocation were detected. Superoxidedismutase (SOD) activity and malondialdehyde (MDA) content were evaluated using the colorimetric method and an automatic microplate reader, respectively. Additionally, the levels of tumor necrosis factor, interleukin (IL)-6, and IL-10 were tested using enzyme-linked immunosorbent assay. The expression of miR-31, HMOX1, NF-κB, HIF-1α,IκB, ZO-1 and Occludin were assessed by reverse transcription quantitative polymerase chain reaction and Western blot analysis. Results: Inhibition of miR-31 decreased intestinal mucosal permeability and intestinal barrier function. The increased levels of miR-31 could cause oxidative damage and affect the expression of inflammatory factors in intestinal tissue of rats. HMOX1 was confirmed as a target gene of miR-31. MiR-31 affected intestinal mucosal permeability and intestinal barrier function, as well as oxidative damage and inflammation level by regulating HMOX1. Down-regulation of miR-31 inhibited NF-κB/HIF-1α pathway related genes by regulating HMOX1 expression. Furthermore, inhibition of miR-31 increased survival rates of rats. Conclusion: Overall, the current study found that inhibition of miR-31 protects against intestinal barrier dysfunction through suppression of the NF-κB/HIF-1α pathway by targeting HMOX1 in rats with sepsis. [ABSTRACT FROM AUTHOR]

The digestion fates of different edible oils are different. The objective of this study was to understand the influences of lipid composition on their digestion fates, and investigate the roles of bile salts (BS) played in emulsified lipid system (whey protein isolate as emulsifier) in the in-vitro small intestine digestion stage. Three typical oils (palm oil (PO), rapeseed oil (RO) and linseed oil (LINO)) were chosen. Results showed that with the BS addition increased from 0.0 to 2.0 mg/mL, the increasing magnitude of the different fatty acid (FA) apparent release rate constants were: PO > RO ≈ LINO. Although the maximum FA release extent changed with BS addition, the order were: PO > RO > LINO. These may probably be attributed to palmitic acids, the most abundant FA in PO, was mostly located on the Sn-1, 3 positions of triacylglycerol (TAG) molecules, which contributed to the pancreatic lipase hydrolysis action. The relatively short chain length and the lower hydrophobicity also favored this process. However, Sn-1, 3 positions of TAGs in RO and LINO were mainly long chain mono- or poly-unsaturated FAs, which restricted the continuous lipid hydrolysis. Furthermore, the lipid composition may also affect the BS behavior on the O/W emulsion droplet surface, thus modulating lipase hydrolysis reaction. These findings can provide some basic understandings of the digestion differences of different oils. [ABSTRACT FROM AUTHOR]

Background and objective Accurate segmentation of liver vessels from abdominal computer tomography angiography (CTA) volume is very important for liver-vessel analysis and living-related liver transplants. This paper presents a novel liver-vessel segmentation and identification method. Methods Firstly, an anisotropic diffusion filter is used to smooth noise while preserving vessel boundaries. Then, based on the gradient symmetry and antisymmetry pattern of vessel structures, optimal oriented flux (OOF) and oriented flux antisymmetry (OFA) measures are respectively applied to detect liver vessels and their boundaries, and further to slenderize vessels. Next, according to vessel geometrical structure, a centerline extraction measure based on height ridge traversal and leaf node line-growing (LNLG) is proposed for the extraction of liver-vessel centerlines, and an intensity model based on fast marching is integrated into graph cuts (GCs) for effective segmentation of liver vessels. Finally, a distance voting mechanism is applied to separate the hepatic vein and portal vein. Results The experiment results on abdominal CTA images show that the proposed method can effectively segment liver vessels, achieving an average accuracy, sensitivity, and specificity of 97.7%, 79.8%, and 98.6%, respectively, and has a good performance on thin-vessel extraction. Conclusions The proposed method does not require manual selection of the centerlines and vessel seeds, and can effectively segment liver vessels and identify hepatic vein and portal vein. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma (OS) is a highly invasive primary malignancy of the bone that is common in children and adolescents. MicroRNAs (miRNAs) are novel diagnostic and predictive biomarkers for cancers. The miRNA miR-3195 is aberrantly expressed in multiple types of tumors. However, the expression levels and biological functions of miR-3195 in OS remain unclear. Methods: Two Gene Expression Omnibus (GEO) datasets (GSE69470 and GSE16088) were used to analyze differentially expressed miRNAs and mRNAs in osteosarcoma cell lines and OS tissues. Quantitative RT-PCR was used to detect the expression levels of miR-3195 and the SRY-box transcription factor 4 (SOX4) mRNA in OS tissues and cell lines. The relationship between miR-3195 and the 3'-upstream region (3'-UTR) in the SOX4 mRNA (predicted through bioinformatics) was analyzed using Pearson's correlation analysis and confirmed by a dual-luciferase reporter gene experiment. Cell counting kit-8 assays, colony formation assays, flow cytometry, wound healing assays, transwell assays, and western blotting were performed to explore the effects of miR-3195 levels on SOX4 affected OS cell biological behavior. Results: Our results revealed that miR-3195 was the most down-regulated miRNA and SOX4 was the most up-regulated mRNA by Bioinformatic analysis. It was further confirmed miR-3195 had low expression, and SOX4 had high expression levels in clinical OS tissue samples; the expression levels of both genes were negatively correlated with each other in OS tissues. Overexpression of miR-3195 in OS cell lines significantly inhibited cell proliferation, migration, and invasiveness, while promoting apoptosis; all these effects were reversed by increasing SOX4 expression levels. We also found that miR-3195 could directly bind with the SOX4 gene and down-regulate SOX4 expression. Conclusions: miR-3195 can modulate proliferation, migration, invasiveness, and apoptosis in OS cells by regulating the SOX4 gene. Thus, the miR-3195/SOX4 signaling may be a novel therapeutic target in OS treatment. [ABSTRACT FROM AUTHOR]

Allergic and autoimmune diseases had been attributed to lack of exposure to biodiversity, an important factor in regulating immune homeostasis in a healthy host. We posit that the microbiome of healthy dairy farmers (DF) will be richer than non-farmers (NF) living in urban settings due to exposure to a greater biodiversity in the dairy environment. However, no studies have investigated the relationships between microbiota of dairy farmers (DF) compared with urban non-farmers (NF). We compared the nasal and oral microbiota of dairy farmers (N_DF, O_DF, respectively) with nasal and oral microbiota of NF in the same geographical area. The N_DF showed high microbial diversity with hundreds of unique genera that reflected environmental/occupational exposures. The nasal and oral microbiomes clustered separately from each other using Principal Coordinate Analysis, and with DF harboring two-fold and 1.5-fold greater exclusive genera in their nose and mouth respectively, than did non-farmers. Additionally, the N_DF group had a lower burden of Staphylococcus spp. suggesting a correlation between higher microbial diversity and competition for colonization by staphylococci. The N_DF samples were negative for the mecA gene, a marker of methicillin-resistance in staphylococci. The lower burden of staphylococci was found to be independent of the abundance of Corynebacterium spp. Exposure to greater biodiversity could enhance microbial competition, thereby reducing colonization with opportunistic pathogens. Future studies will analyze whether exposure to livestock microbiomes offers protection from acute and chronic diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • The major species of the polyphenols derived from rapeseeds were summarized. • The typical biofunctional roles of these polyphenols were elucidated. • The influences of rapeseed oil processing technologies on these polyphenols were elaborated. • Future directions of the studies for illustrating the roles of these polyphenols, and technologies for green manufacturing of rapeseed oil were prospected. The rapeseed (Brassica napus L.) are the important oil bearing material worldwide, which contain wide variety of bioactive components with polyphenolic compounds considered the most typical. The rapeseed polyphenols encompass different structural variants, and have been considered to have many bioactive functions, which are beneficial for the human health. Whereas, the rapeseed oil processing technologies affect their content and the biofunctional activities. The present review of the literature highlighted the major types of the rapeseed polyphenols, and summarized their biofunctional roles. The influences of rapeseed oil processing technologies on these polyphenols were also elucidated. Furthermore, the directions of the future studies for producing nutritional rapeseed oils preserved higher level of polyphenols were prospected. The rapeseed polyphenols are divided into the phenolic acids and polyphenolic tannins, both of which contained different subtypes. They are reported to have multiple biofunctional roles, thus showing outstanding health improvement effects. The rapeseed oil processing technologies have significant effects on both of the polyphenol content and activity. Some novel processing technologies, such as aqueous enzymatic extraction (AEE), subcritical or supercritical extraction showed advantages for producing rapeseed oil with higher level of polyphenols. The oil refining process involved heat or strong acid and alkali conditions affected their stability and activity, leading to the loss of polyphenols of the final products. Future efforts are encouraged to provide more clinic evidence for the practical applications of the rapeseed polyphenols, as well as optimizing the processing technologies for the green manufacturing of rapeseed oils. [ABSTRACT FROM AUTHOR]

In the present study, the phospholipase C (PLC) degumming and water degumming process were studied, respectively, and each was optimized by orthogonal array experimental design; the minimum phosphorus content of PLC degumming was 7.34 ± 0.39 mg/kg, while that of water degumming was 61.54 ± 1.57 mg/kg. Oxidation stability of different oils were analyzed by testing the induction time, and the induction time of degummed oils were a little shorter than crude oil due to the removal of natural phospholipids which acted as antioxidants. Diacylglycerol and triglyceride analysis results showed that PLC degumming was superior to water degumming in increasing the oil yield and decreasing the neutral oil loss during the degumming process. According to the phospholipids composition analysis of degummed oil gums, it could be concluded that PLC was effective to remove the phosphatidylcholine and phosphatidylethanolamine, while having no activity on phosphatidylinositol or phosphatidic acid. [ABSTRACT FROM AUTHOR]

Background: Many new biomedical research articles are published every day, accumulating rich information, such as genetic variants, genes, diseases, and treatments. Rapid yet accurate text mining on large-scale scientific literature can discover novel knowledge to better understand human diseases and to improve the quality of disease diagnosis, prevention, and treatment. Results: In this study, we designed and developed an efficient text mining framework called SparkText on a Big Data infrastructure, which is composed of Apache Spark data streaming and machine learning methods, combined with a Cassandra NoSQL database. To demonstrate its performance for classifying cancer types, we extracted information (e.g., breast, prostate, and lung cancers) from tens of thousands of articles downloaded from PubMed, and then employed Naïve Bayes, Support Vector Machine (SVM), and Logistic Regression to build prediction models to mine the articles. The accuracy of predicting a cancer type by SVM using the 29,437 full-text articles was 93.81%. While competing text-mining tools took more than 11 hours, SparkText mined the dataset in approximately 6 minutes. Conclusions: This study demonstrates the potential for mining large-scale scientific articles on a Big Data infrastructure, with real-time update from new articles published daily. SparkText can be extended to other areas of biomedical research. [ABSTRACT FROM AUTHOR]

Background: Identification and evaluation of incidental findings in patients following whole exome (WGS) or whole genome sequencing (WGS) is challenging for both practicing physicians and researchers. The American College of Medical Genetics and Genomics (ACMG) recently recommended a list of reportable incidental genetic findings. However, no informatics tools are currently available to support evaluation of incidental findings in next-generation sequencing data.Methods: The Wisconsin Hierarchical Analysis Tool for Incidental Findings (WHATIF), was developed as a stand-alone Windows-based desktop executable, to support the interactive analysis of incidental findings in the context of the ACMG recommendations. WHATIF integrates the European Bioinformatics Institute Variant Effect Predictor (VEP) tool for biological interpretation and the National Center for Biotechnology Information ClinVar tool for clinical interpretation.Results: An open-source desktop program was created to annotate incidental findings and present the results with a user-friendly interface. Further, a meaningful index (WHATIF Index) was devised for each gene to facilitate ranking of the relative importance of the variants and estimate the potential workload associated with further evaluation of the variants. Our WHATIF application is available at: http://tinyurl.com/WHATIF-SOFTWARE CONCLUSIONS: The WHATIF application offers a user-friendly interface and allows users to investigate the extracted variant information efficiently and intuitively while always accessing the up to date information on variants via application programming interfaces (API) connections. WHATIF׳s highly flexible design and straightforward implementation aids users in customizing the source code to meet their own special needs. [ABSTRACT FROM AUTHOR]

As the major oxidized triglycerides (ox-TGs), epoxy triglyceride is one of the toxic polar components from deep frying oil. However, the conventional methods are difficult to separate epoxy triglyceride from other ox-TGs due to their similar molecular and structures. To address the problem, a novel magnetic solid-phase extraction approach based on a surface molecularly imprinted polymers was developed. The polymers coated on Fe 3 O 4 nanoparticles (Fe 3 O 4 @MIPs) were synthesized and used as highly selective sorbents for capture epoxy triglyceride from deep frying oil. They have high adsorption capacity (58.3 mg/g), stable equilibrium adsorption time (60 min) and excellent specificity. This method had a satisfactory linear relationship in the range of 0.2–10 mg/L (R 2 = 0.997), and the detection limit of epoxy triglyceride was 0.0599 mg/L. Results indicated that Fe 3 O 4 @MIPs could not only specifically separate epoxy triglycerides, but also provided a potent idea for the separation of other ox-TGs from deep frying oil. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted by researcher Denny and colleagues and published in a 2013 issue of the periodical to conduct a comprehensive phenome-wide association studies (PheWAS) on 3,144 single nucleotide polymorphisms. Topics discussed include drug repositioning which is the process of discovering new indications for existing drugs, and use of flavopiridol, a cyclin-dependent kinase 4 inhibitor and anticancer agent, for the treatment of rheumatoid arthritis.

The genome-wide association study (GWAS) is a powerful approach for studying the genetic complexities of human disease. Unfortunately, GWASs often fail to identify clinically significant associations and describing function can be a challenge. GWAS is a phenotype-to-genotype approach. It is now possible to conduct a converse genotype-to-phenotype approach using extensive electronic medical records to define a phenome. This approach associates a single genetic variant with many phenotypes across the phenome and is called a phenome-wide association study (PheWAS). The majority of PheWASs conducted have focused on variants identified previously by GWASs. This approach has been efficient for rediscovering gene-disease associations while also identifying pleiotropic effects for some single-nucleotide polymorphisms (SNPs). However, the use of SNPs identified by GWAS in a PheWAS is limited by the inherent properties of the GWAS SNPs, including weak effect sizes and difficulty when translating discoveries to function. To address these challenges, we conducted a PheWAS on 105 presumed functional stop-gain and stop-loss variants genotyped on 4235 Marshfield Clinic patients. Associations were validated on an additional 10 640 Marshfield Clinic patients. PheWAS results indicate that a nonsense variant in ARMS2 (rs2736911) is associated with age-related macular degeneration (AMD). These results demonstrate that focusing on functional variants may be an effective approach when conducting a PheWAS. [ABSTRACT FROM AUTHOR]

The virulence protein YopM of the plague bacterium Yersinia pestis has different dominant effects in liver and spleen. Previous studies focused on spleen, where YopM inhibits accumulation of inflammatory dendritic cells. In the present study we focused on liver, where PMN function may be directly undermined by YopM without changes in inflammatory cell numbers in the initial days of infection, and foci of inflammation are easily identified. Mice were infected with parent and ΔyopM-1 Y. pestis KIM5, and effects of YopM were assessed by immunohistochemistry and determinations of bacterial viable numbers in organs. The bacteria were found associated with myeloid cells in foci of inflammation and in liver sinusoids. A new in-vivo phenotype of YopM was revealed: death of inflammatory cells, evidenced by TUNEL staining beginning at d 1 of infection. Based on distributions of Ly6G+, F4/80+, and iNOS+ cells within foci, the cells that were killed could have included both PMNs and macrophages. By 2 d post-infection, YopM had no effect on distribution of these cells, but by 3 d cellular decomposition had outstripped acute inflammation in foci due to parent Y. pestis, while foci due to the ΔyopM-1 strain still contained many inflammatory cells. The destruction depended on the presence of both PMNs in the mice and YopM in the bacteria. In mice that lacked the apoptosis mediator caspase-3 the infection dynamics were novel: the parent Y. pestis was limited in growth comparably to the ΔyopM-1 strain in liver, and in spleen a partial growth limitation for parent Y. pestis was seen. This result identified caspase-3 as a co-factor or effector in YopM's action and supports the hypothesis that in liver YopM's main pathogenic effect is mediated by caspase-3 to cause apoptosis of PMNs. [ABSTRACT FROM AUTHOR]

Objectives: This study explores the mechanism of tanshinone IIA (TSN)-mediated inhibition of myocardial fibrosis by investigating the effect of TSN on transforming growth factor β1 (TGFβ1) signal transduction in rat cardiac fibroblasts (CFs). Materials and Methods: CFs were isolated from neonatal Sprague-Dawley rats by trypsin digestion and differential adhesion and stimulated with 5 ng/mL TGFβ1 and TSN (10-6, 10-5, or 10-4 mol/L). The expression of fibronectin (FN) mRNA in the CFs was determined using reverse transcriptase-polymerase chain reaction and the protein expression of FN and Smads in CFs was detected using Western blot. The intracellular expression and localization of Smads in the CFs were analyzed using immunocytochemistry. Results: TGFβ1 induced the expression of FN and Smads in a time-dependent manner. At the end of the culture treatment, the mRNA expression of FN and the expression of phosphorylated Smad2/3 (p-Smad2/3) increased significantly (P < 0.01). TSN pretreatment (10-5 and 10-4 mol/L) reduced the expression of FN and p-Smad2/3 (P < 0.01) following TGFβ1 stimulation and led to a significant decrease in the nuclear staining intensity and a positive rate of p-Smad2/3 (P < 0.05 and P < 0.01, respectively). Conclusion: The inhibitory effect of TSN on myocardial fibrosis may be associated with its inhibition of TGFβ1-induced Smad2/3 phosphorylation and p-Smad2/3 nuclear translocation, which blocks the TGFβ1/Smad signaling pathway in CFs. [ABSTRACT FROM AUTHOR]

Abstract: Insect chemosensory proteins (CSPs) are proposed to capture and transport hydrophobic chemicals across the sensillum lymph to olfactory receptors (ORs), but this has not been clarified in moths. In this study, we built on our previously reported segment sequence work and cloned the full length CSP19 gene (SinfCSP19) from the antennae of Sesamia inferens by using rapid amplification of cDNA ends. Quantitative real time-PCR (qPCR) assays indicated that the gene was expressed in a unique profile, i.e. predominant in antennae and significantly higher in male than in female. To explore the function, recombinant SinfCSP19 was expressed in Escherichia coli cells and purified by Ni–ion affinity chromatography. Binding affinities of the recombinant SinfCSP19 with 39 plant volatiles, 3 sex pheromone components and 10 pheromone analogs were measured using fluorescent competitive binding assays. The results showed that 6 plant volatiles displayed high binding affinities to SinfCSP19 (Ki=2.12–8.75μM), and more interesting, the 3 sex pheromone components and analogs showed even higher binding to SinfCSP19 (Ki=0.49–1.78μM). Those results suggest that SinfCSP19 plays a role in reception of female sex pheromones of S. inferens and host plant volatiles. [Copyright &y& Elsevier]

Abstract: The influence of coronal streamer background with nested and closed magnetic fields on the of the triggering of coronal mass ejections (CMEs) is investigated in the meridian plane. In the coronal streamers’ background magnetic structure there are three small-scale closed magnetic fields, of which the middle one has a direction opposite to that of the global dipolar field of coronal streamers. The trigger model of CMEs emerges from beneath this small-scale closed magnetic field and possesses a concentric circular structure with radius of a =0.1R s (R s being the solar radius). The direction of the magnetic field in the front half of the CME trigger model is opposite to that of the small-scale closed field and is the same as that of the streamers’ global dipolar field. As revealed by numerical simulation, when the ratio of the plasma pressure at the center of the CME trigger model to the boundary pressure is m ≤2, then the emerging model can trigger CMEs. When m <2, then it cannot. The error in this critical value of 2 is less than 1%. [Copyright &y& Elsevier]

Abstract: The method of Orthogonal Function Series Expansion (OFSE) is generalized and applied to the study of the evolution of the coupling of nondissipative torsional Alfven wave and fast wave in coronal loops. Using this method, the intrinsic angular frequency of the overall wave mode can be described mathematically and that of the Alfven waves along the magnetic lines in the coronal loop during the coupling of the Alfven and fast waves can be analyzed both theoretically and numerically. Also with this method, the relation between the coupling driven term and the Alfven wave resonance may be analyzed. Results of computation reveal the place of appearance of coupling resonance as well as the characteristics of the amplitudes of the Alfven and fast waves. As found by the calculations, if the footpoint driven angular frequency is not equal to the intrinsic angular frequency of the overall wave mode of the coronal loop and when a δ section appears at the place of coupled resonance, the radial gradient of the fast wave''s amplitude is quite large. Sometimes it approximates to a discontinuity, and this is extremely favorable for the dissipation of the fast wave. If the footpoint driven angular frequency is equal to the intrinsic angular frequency of the overall wave mode and when a δ section occurs in the Alfven wave amplitude, abundant small-scale structures appear in the radial direction. Then the location of resonance approximately becomes a discontinuity, very favorable to the dissipation of the Alfven wave. [Copyright &y& Elsevier]

The three-dimensional (3-D) coronal structure in Carrington rotation 1935 in May 1998 is obtained with a 3-D numerical model of ideal MHD equations. In this model, the MacCormack-II scheme is employed for the discretization of the governing equations in the computational domain and the non-reflecting projected-characteristic condition is adopted at the inner boundary in order to keep the simulation stable and the solution self-consistent. The observed photospheric magnetic field in Carrington rotation 1935 is used as the initial guessed magnetic field. The 3-D structure of solar corona acquired by our computation rather well agrees with reality. The results of our computation are as follows: (1) The magnetic field on source surface is nearly a radial one, and the non-radial component is weaker than 2μT near the neutral line. (2) The strength of the radial component of the magnetic field on the source surface does not exhibit large variations except in the vicinity of the neutral line, and this agrees with the observation. (3) The strength of the radial magnetic field component at 1 AU, calculated with inverse square law, agrees with observation better than that given by the potential model. (4) The 3-D numerical coronal structure qualitatively coincides with observation. Besides, the magnetic field dominates global solar wind structure. The density is high and velocity is low in closed magnetic fields or near current sheets, while the density is low and velocity is high in open magnetic fields. [Copyright &y& Elsevier]

Emergent Red Blood Cell (RBC) exchange is indicated in sickle cell disease (SCD) patients with severe acute chest syndrome. However, fully matched RBC units may not be available for patients with multiple RBC antibodies. Intravenous immunoglobulin (IVIG) and steroids were reported for preventing potential delayed hemolytic transfusion reaction (HTR) in simple transfusion of antigen-positive RBCs. We investigated the efficacy and safety of IVIG and steroids in two SCD patients presented with acute chest syndrome receiving RBC exchange with multiple incompatible units. The first patient had multiple historical alloantibodies, including anti-Jsb, although none of them were reactive. IVIG (1 g/kg) was given before and after RBC exchange with methylprednisolone (500 mg IV) one hour before exchange. Her sickle hemoglobin (HbS) was reduced from 89.4% to 17.4% after the exchange with five Jsb-positive units. The patient improved clinically without acute or delayed hemolysis. The second patient had reactive anti-Jsb on two different admissions 18 months apart. Only one of the sixteen units used in the exchanges was Jsb negative. He received the same IVIG regimen during both admissions but 100 mg IV hydrocortisone instead of methylprednisolone. His HbS was reduced from 63.4% to 22.4% after the first exchange. Significant clinical improvements were achieved after both exchanges. No delayed HTR was observed. Our experience of these two patients suggested that IVIG and steroids may be used in preventing potential delayed HTR in some SCD patients with rare antibodies receiving large amounts of antigen-positive RBC products. [ABSTRACT FROM AUTHOR]

The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50 mg (with or without 4-week 100-mg or 200-mg loading dose), 30 mg, or 10 mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50 mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50 mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829. [ABSTRACT FROM AUTHOR]

CoS-Co(OH) 2 heterostructure with conductive polypyrrole (PPy) as the charger transfer mediator were rationally designed and embedded onto the g-C 3 N 4 photocatalyst as the dual noble-metal-free cocatalyst for the first time, for improving the transport, separation and utilization of the photo-generated charge carriers. Notably, CoS, acting as hydrogen evolution reaction (HER) cocatalyst, could not only facilitate the utilization of charge carriers, but also furtherance the charge separation owing to its low flat band potential. Furthermore, the Co(OH) 2 oxygen evolution reaction (OER) cocatalyst exhibited a synergistic effect with the CoS for further improving the charge carriers utilization efficiency. • For the first time, g-C 3 N 4 -PPy-CoS-Co(OH) 2 photocatalyst was synthesized. • PPy acted as photochemical sensitizer and charge carriers mediator. • CoS accepted photo-exited electrons and acted as HER cocatalyst. • Co(OH) 2 received photo-generated holes and acted as OER cocatalyst. CoS-Co(OH) 2 heterostructure with conductive polypyrrole (PPy) as charger transfer mediator were rationally designed and embedded onto the g-C 3 N 4 photocatalyst as the dual noble-metal-free cocatalyst for the first time, for improving the transport, separation and utilization efficiency of the photo-generated charge carriers. Notably, CoS, acting as photocatalytic hydrogen production cocatalyst, not only facilitated the utilization of charge carriers, but also accelerated the charge separation owing to its lower flat band potential. Furthermore, Co(OH) 2 photocatalytic oxygen production cocatalyst exhibited a synergistic effect with CoS for further improving the charge carriers utilization efficiency. Consequently, g-C 3 N 4 -PPy, ternary g-C 3 N 4 -PPy-CoS and quaternary g-C 3 N 4 -PPy-CoS-Co(OH) 2 heterostructures exhibited the photocatalytic hydrogen production activities of 2.49, 23.27 and 46.67 μmol/h, which were 17, 155 and 311-fold in comparison with that of pristine g-C 3 N 4 , respectively. This work provided a hopeful insight for the design of high performance cocatalyst for improving the transport, separation and utilization of photo-exited charge carriers. [ABSTRACT FROM AUTHOR]

• Effects of lipids on serum lipid, colonic SCFAs and colon morphology were studied. • PO and LO had negative effects on serum lipid and colon histology. • An efficient and accurate method was promoted to qualify the colonic SCFAs. • SFA was negatively correlated with colonic isobutyric acid concentration. • Lipids contain high SFA up-regulate the genes related with colon inflammatory. Palm oil (PO), leaf lard oil (LO), rapeseed oil (RO), sunflower oil (SO), and linseed oil (LINO) are the five of the most typical dietary lipids, while few studies have explored and compared their influences on the serum lipid profiles, colonic short chain fatty acids (SCFAs) composition and colon health of Sprague Dawley (SD) rats. Results from the present work showed that PO and LO groups showed significantly higher serum TG and TC level compared with Ctrl group, whereas, the LDL-C/HDL-C and TC/HDL-C ratio were significantly lower in the RO, SO and LINO groups. Different dietary lipid consumption (15% of the normal diet) decreased the colonic SCFAs concentration. The saturated fatty acid (SFA) was negatively correlated, while unsaturated fatty acid (UFA)/SFA ratio was positively correlated, with colonic isobutyric acid concentration. The C18:2ω6 and ω3 fatty acids were positively correlated with colonic butyric acid and isovaleric acid concentration, respectively. Results also demonstrated that PO and LO could decrease the colon villus length and crypt depth, and led to colon injury, which might be due to their high SFAs content. Moreover, results suggested that PO and LO could specifically up-regulate the colon inflammation related gene expression levels and down-regulate the Muc2 expression levels, thus, imposing negative impact on the mucus layers. The present study could provide some information for nutritional evaluation about these dietary lipids. [ABSTRACT FROM AUTHOR]

Background: Plasma levels of von Willebrand factor (VWF) are significantly elevated in patients with coronavirus disease 2019 (COVID-19). However, dynamic changes and prognostic value of this biomarker in hospitalized patients with COVID-19 have not been determined. Methods: A total of 124 patients infected with SARS-CoV-2 were prospectively recruited for the study. Serial blood samples were obtained at the time of admission (D1), 3–4 days following standard-care treatments (D2), and 1–2 days prior to discharge or any time collected prior to death (D3). Plasma VWF antigen, ADAMTS13 antigen, and ADAMTS13 proteolytic activity, as well as the ratio of VWF/ADAMTS13 were determined, followed by various statistical analyses. Results: On admission, plasma levels of VWF in COVID-19 patients were significantly elevated compared with those in the healthy controls, but no statistical significance was detected among patients with different disease severity. Plasma ADAMTS13 activity but not its antigen levels were significantly lower in patients with severe or critical COVID-19 compared with that in other patient groups. Interestingly, the ratios of plasma VWF antigen to ADAMTS13 antigen were significantly higher in patients with severe or critical COVID-19 than in those with mild to moderate disease. More importantly, plasma levels of VWF and the ratios of VWF/ADAMTS13 were persistently elevated in patients with COVID-19 throughout hospitalization. Kaplan–Meier and Cox proportional hazard regression analyses demonstrated that an increased plasma level of VWF or ratio of VWF/ADAMTS13 at D2 and D3 was associated with an increased mortality rate. Conclusions: Persistent endotheliopathy, marked by the elevated levels of plasma VWF or VWF/ADAMTS13 ratio, is present in all hospitalized patients following SARS-CoV-2 infection, which is strongly associated with mortality. [ABSTRACT FROM AUTHOR]

In this study, peanut oil was prepared by cold pressing (temperature under 60 °C), hot pressing (temperature above 105 °C), and enzyme‐assisted aqueous extraction technology. Influences of an extraction technology on the oil fatty acid composition and the content of minor bioactive compounds, including tocopherols, polyphenols, and squalene, were investigated in detail. High‐fat‐diet Sprague–Dawley (SD) rat model was then established to probe the impact of cold‐pressed peanut oil (CPO), hot‐pressed peanut oil (HPO), and enzyme‐assisted aqueous‐extracted peanut oil (EAO) on lipid metabolism outcomes, to explore influences of different extraction technologies on lipid functional quality. Results showed that oleic acid was the predominate fatty acid in the EAO (52.57 ± 0.11%), which was also significantly higher (P < 0.05) than CPO and HPO. The HPO showed higher total tocopherol and polyphenol contents (206.84 ± 6.93 mg/kg and 47.87 ± 6.50 mg GA/kg, respectively) than CPO and EAO (P < 0.05). However, the squalene content in CPO was 475.47 ± 12.75 mg/kg, which was the highest among the three oils (P < 0.05). The animal experiment results revealed that EAO could be more prone to induce lipid accumulation in the liver, which may likely to cause nonalcoholic fatty liver disease. However, the serum lipid profiles indicated that the CPO was more beneficial than the EAO and HPO in lowering the serum low‐density lipoprotein cholesterol, alanine aminotransferase, and aspartate aminotransferase contents, and increasing the high‐density lipoprotein cholesterol content. All of our efforts indicated that an extraction technology can affect the peanut oil lipid fatty acid composition, the bioactive compounds content, and, correspondingly, the lipid metabolism in SD rats. [ABSTRACT FROM AUTHOR]

Human cytosolic sulfotransferase 1A1 ( SULT1A1 ) is considered to be one of the most important SULT isoforms for metabolism, detoxification, and carcinogenesis. This theory is driven by observations that SULT1A1 is widely expressed in multiple tissues and acts on a wide range of phenolic substrates. SULT1A1 is subject to functional common copy number variation (CNV) including deletions or duplications. However, it is less clear how SULT1A1 CNV impacts health and disease. To better understand the biological role of SULT1A1 in human health, we genotyped CNV in 14,275 Marshfield Clinic patients linked to an extensive electronic health record. Since SULT1A1 is linked to steroid metabolism, select serum steroid hormones were measured in 100 individuals with a wide spectrum of SULT1A1 CNV genotypes. Furthermore, comprehensive phenome-wide association studies (PheWAS) were conducted using diagnostic codes and clinical text data. For the first time, individuals homozygous null for SULT1A1 were identified in a human population. Thirty-six percent of the population carried >2 copies of SULT1A1 whereas 4% had ≤ 1 copy. Results indicate SULT1A1 CNV was negatively correlated with estrone-sulfate to estrone ratio predominantly in males (E1S/E1; p = 0.03, r = −0.21) and may be associated with increased risk for common allergies. The effect of SULT1A1 CNV on circulating estrogen metabolites was opposite to the predicted CNV-metabolite trend based on enzymatic function. This finding, and the potential association with common allergies reported herein, warrants future studies. [ABSTRACT FROM AUTHOR]

Transient hyperphosphatasemia, characterized by isolated highly elevated alkaline phosphatase (ALP) activity in the absence of liver or bone disease, is typically seen in children but rarely in adults. Here we report highly elevated ALP activity in a complicated multiple-organ transplant patient due to benign transient hyperphosphatasemia. A 54-year-old male had a complicated past medical history including a bilateral lung transplant for cystic fibrosis in 2006, colonic resection due to colon cancer in December 2011 and subsequent chemotherapy which ended in June 2022. He also had combined liver and kidney transplant in 2022 at our academic medical center. Post-transplant, he was treated with triple drug immunosuppressant therapy (tacrolimus, mycophenolic acid, and prednisone). Although his alkaline phosphatase (ALP) activity was 83 U/L, it continued to increase three months after combined liver and kidney transplant even though other liver enzymes were mildly elevated but total bilirubin remained within their reference ranges. Flecainide was discontinued but his ALP remained high, peaking at 5904 U/L. Finally, lansoprazole, ergocalciferol (vitamin D2) and vitamin E supplement were discontinued as nonessential medications, and coincidently ALP activity started to decline. After ruling out all possibilities that may cause elevated ALP, we concluded that this is a rare case of benign transient hyperphosphatasemia in an adult transplant recipient. [ABSTRACT FROM AUTHOR]

Rapeseed polyphenols have cardiovascular protective effects. Sinapine, one main rapeseed polyphenol, possesses antioxidative, anti-inflammatory, and antitumor properties. However, no research has been published about the role of sinapine in alleviating macrophage foaming. This study aimed to reveal the macrophage foaming alleviation mechanism of sinapine by applying quantitative proteomics and bioinformatics analyses. A new approach was developed to retrieve sinapine from rapeseed meals by using hot-alcohol-reflux-assisted sonication combined with anti-solvent precipitation. The sinapine yield of the new approach was significantly higher than in traditional methods. Proteomics was performed to investigate the effects of sinapine on foam cells, and it showed that sinapine can alleviate foam cell formation. Moreover, sinapine suppressed CD36 expression, enhanced the CDC42 expression, and activated the JAK2 and the STAT3 in the foam cells. These findings suggest that the action of sinapine on foam cells inhibits cholesterol uptake, activates cholesterol efflux, and converts macrophages from pro-inflammatory M1 to anti-inflammatory M2. This study confirms the abundance of sinapine in rapeseed oil by-products and elucidates the biochemical mechanisms of sinapine that alleviates macrophage foaming, which may provide new perspectives for reprocessing rapeseed oil by-products. [ABSTRACT FROM AUTHOR]

The title compound, C16H15N3O6, exhibits weak intermolecular C—H...O and O—H...O hydrogen bonds, which stabilize the structure. π–π stacking interactions are also found, the centroid-to-centroid distance within the stacks being 3.4401 Å. The title compound represents a new derivative of 1, 8-naphthalimides. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of bempedoic acid on glycaemic and lipid variables in patients with hypercholesterolaemia. Methods: A patient‐level pooled analysis of four phase 3, randomized, double‐blind, placebo‐controlled trials evaluated changes in glycaemia, change from baseline in LDL‐C, and adverse events. Patients (N = 3621) on maximally tolerated statins were randomized 2:1 to oral bempedoic acid 180 mg or placebo once daily for 12 to 52 weeks with the results analysed by baseline glycaemic status (diabetes, prediabetes, or normoglycaemia). Results: The annual rate of new‐onset diabetes for bempedoic acid versus placebo in patients with normoglycaemia at baseline (n = 618) was 0.3% versus 0.8%, and for patients with prediabetes at baseline (n = 1868) it was 4.7% versus 5.9%. In patients with diabetes or prediabetes, bempedoic acid significantly (P <.0001) reduced HbA1c by −0.12% and −0.06%, respectively, and did not worsen fasting glucose versus placebo. Bempedoic acid significantly and consistently lowered LDL‐C levels versus placebo, regardless of baseline glycaemic status (placebo‐corrected difference range, −17.2% to −29.6%; P <.001 for each stratum). The safety of bempedoic acid was comparable with placebo and similar across glycaemic strata. Conclusions: Bempedoic acid significantly lowered LDL‐C across glycaemic strata and did not worsen glycaemic variables or increase the incidence of new‐onset diabetes versus placebo over a median follow‐up of 1 year. [ABSTRACT FROM AUTHOR]

Pioglitazone as monotherapy and in combination with sulfonylurea, metformin, or insulin has consistently demonstrated improved glycaemic and lipid parameters in patients with type 2 diabetes mellitus. Objective: We performed a subanalysis to examine the effect of pioglitazone on glycaemia and lipids in patients <65 and ≥65 years of age in two double-blind, placebo-controlled monotherapy studies and in three separate multi-centre trials. Method: In Study 1, 197 patients were randomised to receive pioglitazone 30 mg/day or placebo for 16 weeks. Study 2 was a forced dose-titration trial in patients randomised to receive pioglitazone 7.5/15/30 mg/day, pioglitazone 15/30/45 mg/day, or placebo daily for 26 weeks. Each of the lower dosages was given for at least 4 weeks and the highest dosage for 16 weeks. The three combination studies evaluated efficacy of pioglitazone 30 or 45 mg/day over a 24-week period in combination with sulfonylureas, metformin, or insulin. Results: In both placebo-controlled monotherapy studies, at 16 weeks, and at maximum pioglitazone dosage, 0.53–0.55% and 0.57–1.27% mean reductions from baseline in glycosylated haemoglobin (HbA1c) were seen in patients aged <65 (n = 225) and ≥65 (n = 45) years, respectively. There were statistically significant differences between the placebo and pioglitazone groups in each age cohort. Similar effects were observed in fasting plasma glucose (FPG) levels, with 2.03–2.59 mmol/L and 3.20–4.44 mmol/L mean reductions from baseline, respectively, which were significantly different from the changes in the placebo group, but there was no difference between pioglitazone groups. At treatment endpoint in combination trials, pioglitazone added to sulfonylurea produced a mean decrease in HbA1c of 0.78–1.61%, and 1.64–1.96% in patients aged <65 (n = 557) and ≥65 (n = 115) years, respectively. Pioglitazone added to metformin produced a mean decrease in HbA1c of 0.78–1.03% and 0.78–0.98% in patients aged <65 (n = 686) and ≥65 (n = 112) years, respectively. Pioglitazone added to insulin produced a mean decrease in HbA1c of 1.13–1.37% and 1.39–1.66% in patients aged <65 (n = 500) and ≥65 (n = 156) years, respectively. In patients aged ≥65 years, hypoglycaemia was observed in 1 of 14 patients and in 0 of 13 patients in the two monotherapy studies. In the combination studies, the incidence of hypoglycaemia among patients aged ≥65 years was as follows: 26.7–28.8% combined with sulfonylurea; 0–4.4% combined with metformin; and 53.4–56.4% combined with insulin. Conclusion: Pioglitazone monotherapy, or added to a sulfonylurea, metformin, or insulin demonstrated no significant differences in effectiveness while exhibiting similar adverse events in patients aged ≥65 years compared with patients aged <65 years. Well-controlled randomised clinical trials are recommended to confirm the impact of pioglitazone therapy on the glycaemic and lipid control in elderly patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate two trials of combination therapy, pioglitazone together with metformin or sulfonylurea, for Type 2 diabetes mellitus and to examine how pretrial antidiabetic therapies may have influenced the results. Subjects and Methods: The results of two published trials that examine combination therapy, pioglitazone plus metformin or pioglitazone plus sulfonylurea were analyzed. A post hoc analysis was performed in which patients from both of these trials were subdivided on the basis of their oral antidiabetic therapy before enrollment into the trials. Those subsets receiving pretrial therapy with a sulfonylurea plus metformin — and discontinuing one of the agents before randomization — were compared to those receiving only one of the agents before enrollment. Results: Patients in the combination pioglitazone (30 mg/day) plus metformin therapy arm of one trial, who entered with stable metformin monotherapy, experienced a significant decrease in glycosylated hemoglobin (HbA1C) levels during the 16-week course of the trial (−1.0±0.1 [mean±S.E.] percentage points; P<.05). In contrast, those in the same arm of the trial whose pretrial therapy included metformin plus a sulfonylurea — and who discontinued the sulfonylurea before enrollment — experienced no significant change in HbA1C levels (0.2±0.2 percentage points; P>.05). The difference between groups was significant (P<.001). Patients in the combination pioglitazone (15 or 30 mg/day) plus sulfonylurea therapy arm of the other trial, who entered the trial on stable sulfonylurea monotherapy, experienced significant decreases in HbA1C levels (−1.0±0.1 and −1.4±0.1 percentage points, respectively, for the 15- and 30-mg pioglitazone arms; P<.05). Those in the same arm whose pretrial therapy included sulfonylurea plus metformin — and who discontinued the metformin before enrollment — experienced no significant change in HbA1C levels. Differences between the groups separated on the basis of pretrial antidiabetic regimen were significant (P<.001). Conclusions: The efficacy of pioglitazone as an add-on in combination therapy (with metformin or a sulfonylurea) is likely to be greater than in previous reports, because those trial results were influenced by treatment regimens used by a portion of the patients before enrollment. Trials of oral hypoglycemic agents must be carefully constructed to consider the effects of agents given prior to the trial. [Copyright &y& Elsevier]

Background Mass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing amidst widespread transmission during the coronavirus disease-2019 (COVID-19) pandemic. Disease phenotypes of SARS-CoV-2 exposure occurring around the time of vaccine administration have not been described. Methods Two-dose (14 days apart) vaccination regimen with formalin-inactivated whole virion SARS-CoV-2 in golden Syrian hamster model was established. To investigate the disease phenotypes of a 1-dose regimen given 3 days prior (D-3), 1 (D1) or 2 (D2) days after, or on the day (D0) of virus challenge, we monitored the serial clinical severity, tissue histopathology, virus burden, and antibody response of the vaccinated hamsters. Results The 1-dose vaccinated hamsters had significantly lower clinical disease severity score, body weight loss, lung histology score, nucleocapsid protein expression in lung, infectious virus titers in the lung and nasal turbinate, inflammatory changes in intestines, and a higher serum neutralizing antibody or IgG titer against the spike receptor-binding domain or nucleocapsid protein when compared to unvaccinated controls. These improvements were particularly noticeable in D-3, but also in D0, D1, and even D2 vaccinated hamsters to varying degrees. No increased eosinophilic infiltration was found in the nasal turbinate, lung, and intestine after virus challenge. Significantly higher serum titer of fluorescent foci microneutralization inhibition antibody was detected in D1 and D2 vaccinated hamsters at day 4 post-challenge compared to controls despite undetectable neutralizing antibody titer. Conclusions Vaccination just before or soon after exposure to SARS-CoV-2 does not worsen disease phenotypes and may even ameliorate infection. [ABSTRACT FROM AUTHOR]

In the work, zein-yeast carboxymethyl glucan (ZY) particles were fabricated by a novel ultrasonic assisted anti-solvent precipitation (ASP) method, which was a good delivery system for resveratrol. The particle size and zeta-potential of ZY samples were detected by Zetasizer Pro analyzer, they gradually increased as the mass ratio of zein and yeast carboxymethyl glucan (YCG) changed from 10:1 to 10:5. The intermolecular interactions were investigated by zeta-potentiometric analyzer, Fourier transform infrared spectroscopy and fluorescence spectroscopy. Electrostatic interaction, hydrogen bonding and hydrophobic effects between zein and YCG molecules were identified as the main driving forces in the formation of ZY particles. The optimized ZY (10:3) binary particles were used as delivery system for encapsulating and protecting resveratrol. They had high encapsulation efficiency (85.4 %) and loading capacity (6.1 %), and increased the retention rate of resveratrol by 2.10 and 1.21 folds after exposure to light and heat conditions, effectively protect resveratrol against light and thermal degradation. These particles also delayed the release of resveratrol in simulated gastrointestinal digestion, which might improve its oral bioavailability. In conclusion, ZY binary particles could be regarded as a useful and promising delivery vehicle, which might contribute to the application of hydrophobic bioactive ingredients in functional foods. [Display omitted] • Ultrasonic assisted anti-solvent precipitation was used to fabricate ZY particles. • Molecular interaction mechanism of zein and yeast carboxymethyl glucan was studied. • ZY particles were suitable delivery vehicle of resveratrol with high EE and LC. • ZY particles increased light and thermal stability of resveratrol by 2.10 and 1.21 folds. • ZY particles controlled-release resveratrol in simulated gastrointestinal digestion. [ABSTRACT FROM AUTHOR]

Background: The microparticle content (MP%) of apheresis platelets-a marker of platelet activation-is influenced by donor factors and by external stressors during collection and storage. This study assessed the impact of apheresis technology and other factors on the activation status (MP%) of single-donor apheresis platelets.Study Design and Methods: Data from six US hospitals that screened platelets by measuring MP% through dynamic light scattering (ThromboLUX) were retrospectively analyzed. Relative risks (RRs) were derived from univariate and multivariable regression models, with activation rate (MP% ≥15% for plasma-stored platelets; ≥10% for platelet additive solution [PAS]-stored platelets) and MP% as outcomes. Apheresis platform (Trima Accel vs Amicus), storage medium (plasma vs PAS), pathogen reduction, storage time, and testing location were used as predictors.Results: Data were obtained from 7511 platelet units collected using Trima (from 16 suppliers, all stored in plasma, 20.0% were pathogen-reduced) and 2456 collected using Amicus (from four different collection facilities of one supplier, 65.0% plasma-stored, 35.0% PAS-stored, none pathogen-reduced). Overall, 30.0% of Trima platelets were activated compared to 45.6% of Amicus platelets (P < .0001). Multivariable analysis identified apheresis platform as significantly associated with platelet activation, with a lower activation rate for Trima than Amicus (RR: 0.641, 95% confidence interval [CI]: 0.578; 0.711, P < .0001) and a 6.901% (95% CI: 5.926; 7.876, P < .0001) absolute reduction in MP%, when adjusting for the other variables.Conclusion: Trima-collected platelets were significantly less likely to be activated than Amicus-collected platelets, irrespective of the storage medium, the use of pathogen reduction, storage time, and testing site. [ABSTRACT FROM AUTHOR]

Toxins produced by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) contribute to virulence. We developed a statistical approach to determine an optimum sequence of antimicrobials to treat CA-MRSA infections based on an antimicrobial's ability to reduce virulence. In an in vitro pharmacodynamic hollow fiber model, expression of six virulence genes (lukSF-PV, sek, seq, ssl8, ear, and lpl10) in CA-MRSA USA300 was measured by RT-PCR at six time points with or without human-simulated, pharmacokinetic dosing of five antimicrobials (clindamycin, minocycline, vancomycin, linezolid, and trimethoprim/sulfamethoxazole (SXT)). Statistical modeling identified the antimicrobial causing the greatest decrease in virulence gene expression at each time-point. The optimum sequence was SXT at T0 and T4, linezolid at T8, and clindamycin at T24–T72 when lukSF-PV was weighted as the most important gene or when all six genes were weighted equally. This changed to SXT at T0–T24, linezolid at T48, and clindamycin at T72 when lukSF-PV was weighted as unimportant. The empirical p-value for each optimum sequence according to the different weights was 0.001, 0.0009, and 0.0018 with 10,000 permutations, respectively, indicating statistical significance. A statistical method integrating data on change in gene expression upon multiple antimicrobial exposures is a promising tool for identifying a sequence of antimicrobials that is effective in sustaining reduced CA-MRSA virulence. [ABSTRACT FROM AUTHOR]

External beam radiotherapy (EBRT) with neoadjuvant/adjuvant androgen deprivation therapy (ADT) is an established treatment option to prolong survival for patients with intermediate- and high-risk prostate cancer (PCa). Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, was evaluated in this clinical setting in comparison with degarelix, an injectable GnRH antagonist. To evaluate the safety and efficacy of relugolix to achieve and maintain castration. A phase 2 open-label study was conducted in 103 intermediate-risk PCa patients undergoing primary EBRT and neoadjuvant/adjuvant ADT between June 2014 and December 2015. Patients randomly assigned (3:2) to 24-wk treatment with either daily oral relugolix or 4-wk subcutaneous depot degarelix (reference control). The primary endpoint was the rate of effective castration (testosterone <1.73 nmol/l) in relugolix patients between 4 and 24 wk of treatment. Secondary endpoints included rate of profound castration (testosterone <0.7 nmol/l), prostate-specific antigen (PSA) levels, prostate volume, quality of life (QoL) assessed using the Aging Males' Symptoms scale, and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (30-item EORTC core questionnaire [EORTC QLQ-C30] and 25-item EORTC prostate cancer module [EORTC QLQ-PR25]) questionnaires, and safety. No formal statistical comparisons with degarelix were planned. Castration rates during treatment were 95% and 82% with relugolix and 89% and 68% with degarelix for 1.73 and 0.7 nmol/l thresholds, respectively. Median time to castration in the relugolix arm was 4 d. During treatment, PSA levels and prostate volumes were reduced in both groups. Three months after discontinuing treatment, 52% of men on relugolix and 16% on degarelix experienced testosterone recovery (statistical significance of differences not tested). Mean and median QoL scores improved following treatment discontinuation. The most common adverse event was hot flush (relugolix 57%; degarelix 61%). Lack of blinding was a potential limitation. Relugolix achieved testosterone suppression to castrate levels within days and maintained it over 24 wk with a safety profile consistent with its mechanism of action. Oral once-daily relugolix may be a novel oral alternative to injectable androgen deprivation therapies. The phase 2 study C27003 demonstrated relugolix, an oral gonadotropin-releasing hormone antagonist, achieves and maintains testosterone castration for 24 wk in >90% of men with localised intermediate- and high-risk prostate cancer requiring neoadjuvant and/or adjuvant androgen deprivation therapy to external beam radiation therapy. [ABSTRACT FROM AUTHOR]

Pheromone‐binding proteins (PBPs) are thought to bind and transport sex pheromones onto the olfactory receptors on the dendrite membrane of olfactory neurons, and thus play a vital role in sex pheromone perception. However, the function of PBPs has rarely been demonstrated in vivo. In this study, two PBPs (PBP1 and PBP3) of Chilo suppressalis, one of the most notorious pyralid pests, were in vivo functionally characterized using insects with the PBP gene knocked out by the CRISPR/Cas9 system. First, through direct injection of PBP‐single guide RNA (sgRNA)/Cas9 messenger RNA into newly laid eggs, a high rate of target‐gene editing (checked with polled eggs) was induced at 24 h after injection, 21.3% for PBP1‐sgRNA injected eggs and 19.5% for PBP3‐sgRNA injected eggs. Second, by an in‐crossing strategy, insects with mutant PBP1 or PBP3 (both with a premature stop codon) were screened, and homozygous mutants were obtained in the G3 generation. Third, the mutant insects were measured for electroantennogram (EAG) response to female sex pheromones. As a result, both PBP mutant males displayed significant reduction in EAG response, and this reduction in PBP1 mutants was higher than that in PBP3 mutants, indicating a more important role of PBP1. Finally, the relative importance of two PBPs and the possible off target effect induced by sgRNA‐injection are discussed. Taken together, our study provides a deeper insight into the function of and interaction between different PBP genes in sex pheromone perception of C. suppressalis, as well as a valuable reference in methodology for gene functional study in other genes and other moth species. [ABSTRACT FROM AUTHOR]