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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]

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]

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]

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]

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]

Although in the majority of patients (90%), the bite wound of brown recluse spider resolves spontaneously, some patients may experience a severe reaction requiring hospitalization. A 25‐year‐old male developed severe hemolytic anemia, jaundice, and other complications following a brown recluse spider bite on his posterior right thigh. He was treated with methylprednisolone, antibiotics, and red blood cells (RBCs) transfusion without response. Therapeutic plasma exchange (TPE) was added to the treatment regimen, and his hemoglobin (Hb) was eventually stabilized, leading to significant clinical improvement. The beneficial effect of TPE in the current case was compared to three other reported cases. We recommend close monitoring of Hb levels in patients with systemic loxoscelism during the first week after brown recluse spider bite and early implementation of TPE in the management of severe acute hemolysis when patients do not respond to usual treatment modalities and RBC transfusion. [ABSTRACT FROM AUTHOR]

Aiming at the problem that the current traditional methods can not effectively analyze the camouflage of human moving objects in real time, which leads to the poor accuracy of human motion prediction, this paper proposes an analysis method of camouflage model of human moving objects based on bionic leaves of marine plants, Firstly, establishing the index system of human motion target parameters. On this basis, the indexes of human motion objects were compared and the scores were given. According to the scores, the constitution parameter matrix was judged and the weight value of constitution index was calculated. Moreover, the reliability of constitution parameter and the body quality index were used to test the consistency, so that the combined weight of constitution was obtained. Furthermore, it was necessary to analyze and study the constitution elements of constitution health and the growth difference, and thus to complete the calculation of weight coefficient of constitution index. Finally, the change model of constitution parameters was built. Experimental results show that the results of proposed method are consistent with the actual results, so the proposed method has the advantages of high effectiveness. [ABSTRACT FROM AUTHOR]

Visible light has been widely studied for possible applications in food industry as being a kind of clean energy. Presently, the influences of illumination pretreatment on soybean oil quality followed by conventional activated clay bleaching, including the oil color, fatty acid composition, oxidation stability, and micronutrient content, were investigated. Results demonstrated that the illumination pretreatment increased the color differences between the non-illuminated and illuminated soybean oils, which indicated that the light exposure could improve the decoloring effects. The fatty acids composition and the peroxide value (POV) and oxidation stability index (OSI) of the soybean oils showed little changes during this process. Although the illumination pretreatment affected the content of lipid-soluble micronutrients, including phytosterols and tocopherols, no significant differences could be observed (p > 0.05). Moreover, it showed that the illumination pretreatment showed significant effects for decreasing the following activated clay bleaching temperature, indicating the energy saving potential of this novel soybean oil decoloring process. The present study might provide new insights for developing eco-friendly and efficient vegetable oil bleaching technology. [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]

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]

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]

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]

Background: Staphylococcus aureus, the most common pathogen in skin and soft tissue infections (SSTI), harbors many well-characterized virulence genes. However, the expression of many of them in SSTIs is unknown. In this study, S. aureus virulence genes expressed in SSTI were investigated. Methods: Fifty-three subjects presenting to the outpatient's care and emergency departments with a purulent SSTI at two medical centers in Wisconsin, USA, were enrolled in the study. Total mRNA was extracted from the purulent or swab materials, made into cDNA and sequenced on MiSeq platform. The relative cDNA counts to gmk and identifications of the transcripts were carried out with respect to USA300 reference genome and using SAMTOOLS v.1.3 and BWA, respectively. Result: A significantly higher cDNA count was observed for many of the virulence and regulatory gene transcripts in the pus samples compared to the swab samples relative to the cDNA counts for gmk, a housekeeping gene. They were for lukS-PV (18.6 vs. 14.2), isaA (13.4 vs. 8.5), ssaA (4.8 vs. 3.1), hlgC (1.4 vs. 1.33), atl (17.7 vs. 8.33), clfA (3.9 vs. 0.83), eno (6.04 vs. 3.16), fnbA (5.93 vs. 0.33), saeS (6.3 vs. 1.33), saeR (5.4 vs. 3.33) and agrC (5.6 vs. 1.5). Conclusions: A relative increase in the transcripts of several toxins, adhesion and regulatory genes with respect to a gmk in purulent materials suggests their role in situ during SSTIs, perhaps in an orchestrated manner. [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]

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]

The development of earth-abundant cocatalysts with confined size on suitable conductive supports is of high importance for facilitating solar energy conversion using semiconductors. In this work, a green redox relay reaction between FeCl3 and a pyrrole (Py) monomer was developed for the synthesis of g-C3N4–PPy–FeP, in which FeCl3 realized the formation of PPy over graphitic carbon nitride, and the as-formed PPy confined and tightly supported Fe ions, which were then transformed into the nanosized FeP of diameter less than 5 nm. A highly porous morphology was obtained by inserting well-dispersed g-C3N4 into PPy, accompanied by conductive PPy and nanosized FeP acting as a mediator of charge carriers and high-performance cocatalyst, respectively. Consequently, optimal g-C3N4–PPy–FeP demonstrated a photocatalytic hydrogen evolution activity 6 and 20 times larger than that of g-C3N4 singly loaded separately with PPy and FeP, respectively, under visible light irradiation. [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]

A rational design of the morphology and configuration of the photocatalyst heterostructure is of great importance for solar energy conversion. This work reported the uniform distribution of CdS nanoparticles over the MOF-derived porous NiO skeleton, thanks to the PVP surface modification, with the residual carbon acting as a conductive medium of charge carriers. The formation of CdS-porous NiO exhibited an excellent photocatalytic hydrogen evolution activity of 7.12 mmol h−1 g−1, and was further improved to 14.25 mmol h−1 g−1 after the PVP surface modification. Impressively, even in the absence of a sacrificial agent, the well-dispersed CdS–NiO heterostructure exhibited a photocatalytic hydrogen production activity of 29.92 and 6.83 μmol h−1 g−1 with the production of a considerable amount of H2O2 under UV-visible and visible light irradiation, respectively. [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]

The design of highly effective noble metal-free cocatalysts plays an extremely important role in improving the photocatalytic solar energy conversion. Herein, we designed and synthesized a novel heterostructure form of MoS2–transition metals (Fe, Co, and Ni) on g-C3N4 nanosheets for obtaining a significant enhancement in the photocatalytic activity for hydrogen production and pollutant disposal. The electrochemical characterization and time-resolved photoluminescence results indicated that the unique tunable feature of the MoS2–transition metals greatly reduced the hydrogen evolution reaction (HER) overpotential, increased the separation, transport and utilization efficiency of the photo-generated charge carriers, and displayed a synergistic effect in improving the electrocatalytic and photocatalytic HER performances. The ternary g-C3N4–MoS2–metals exhibited extremely high photocatalytic HER rates of 1.7, 4.1, and 5.12 mmol h−1 g−1 for g-C3N4–MoS2–Fe, g-C3N4–MoS2–Co and g-C3N4–MoS2–Ni, respectively, which were 2.7, 4.7 and 5.3 times larger than the sum of the photocatalytic HER activities of g-C3N4–MoS2 and the corresponding g-C3N4–metals. This work provides a facile and effective strategy for improving photocatalytic energy conversion using only earth-abundant non-noble cocatalyst heterostructures. [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]

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]

Orthaga achatina (Lepidoptera: Pyralidae) is the most serious pest in south China of camphor trees, Cinnamomum camphora (L.) Presl, an important urban tree species. Gas chromatography-electroantennographic detection (GC-EAD) of the sex pheromone of O. achatina showed three EAD-active components. Coupled gas chromatography/mass spectrometry analyses identified these as (Z)-11-hexadecenol (Z11-16:OH), (Z)-11-hexadecenyl acetate (Z11-16:OAc), and (3Z,6Z,9Z,12Z,15Z)-tricosapentaene (Z3,Z6,Z9,Z12,Z15-23:H). In field tests using different combinations of the three compounds, male moths were attracted to a mixture of Z11-16:OAc and Z3,Z6,Z9,Z12,Z15-23:H, but less attracted to other blends. Further field tests with different ratios of the two compounds determined the optimal ratio of the binary blend as 500:250. The addition of Z11-16:OH to Z11-16:OAc, or to the binary mixture of Z11-16: OAc and the pentaene did not yield higher catches. This shows that O. achatina uses a mixture of Type I and Type II sex pheromone components. Orthaga achatina is the third Pyraloidea species found to utilize Z3,Z6,Z9,Z12,Z15-23:H as a sex pheromone component. [ABSTRACT FROM AUTHOR]

Motivation: Pedigree analysis is a longstanding and powerful approach to gain insight into the underlying genetic factors in human health, but identifying, recruiting and genotyping families can be difficult, time consuming and costly. Development of high throughput methods to identify families and foster downstream analyses are necessary. Results: This paper describes simple methods that allowed us to identify 173 368 family pedigrees with high probability using basic demographic data available in most electronic health records (EHRs). We further developed and validate a novel statistical method that uses EHR data to identify families more likely to have a major genetic component to their diseases risk. Lastly, we showed that incorporating EHR-linked family data into genetic association testing may provide added power for genetic mapping without additional recruitment or genotyping. The totality of these results suggests that EHR-linked families can enable classical genetic analyses in a high-throughput manner. [ABSTRACT FROM AUTHOR]

Aim To investigate the effect of fasiglifam on glycaemic control in people with type 2 diabetes mellitus ( T2DM). Methods In total, 421 people with T2DM and glycated haemoglobin ( HbA1c) ≥7.0% and ≤10.5% who had received only diet and exercise treatment for ≥12 weeks prior to screening were randomized to receive fasiglifam 25 or 50 mg or placebo. The primary efficacy endpoint was change from baseline in HbA1c at week 24. Results The mean participant age was 53.5 years, mean baseline body mass index 32.3 kg/m2, and mean baseline HbA1c level 8.05%. Least squares mean changes in HbA1c from baseline to week 24 were: −0.93% (fasiglifam 50 mg), −0.65% (fasiglifam 25 mg) and −0.17% (placebo). Treatment-emergent adverse events ( TEAEs) occurred in 53.3%, 48.2% and 39.9% of participants receiving fasiglifam 25 mg, fasiglifam 50 mg, and placebo, respectively. Three participants in each group experienced a serious adverse event ( AE). Nine participants had alanine aminotransferase ( ALT) elevations >3× upper limit of normal: 5 (3.6%) in the fasiglifam 25-mg group, 4 (2.8%) in the fasiglifam 50-mg group, and none in the placebo group. Conclusions The data indicate that fasiglifam effectively reduced HbA1c from baseline for 24 weeks in participants with T2DM. The incidence of TEAEs was higher in the fasiglifam groups; however, the incidence of serious AEs was low overall and similar between groups. ALT elevations were observed only in the fasiglifam groups, which contributed to the decision to terminate the fasiglifam programme after completion of the present study. [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]

Species-specific sex pheromone is biosynthesized and released in most female moths as a chemical cue in mating communication. However, information on genes involved in this pathway is limited. The beet armyworm, Spodoptera exigua, is a cosmopolitan agricultural pest that causes severe economic losses to many crops. In China, the female sex pheromones in sex pheromone glands (PGs) of S. exigua have been measured which comprises (Z,E)-9,12-tetradecadienyl acetate, (Z)-9-tetradecen-l-ol, (Z)-9-tetradecenyl acetate, and (Z,E)-9,12-tetradecadien-1-ol in a ratio of 47:18:18:17. Fifty-nine putative genes related to sex pheromone biosynthesis were identified in the present study by sequencing and analyzing the sex pheromone gland (PG) transcriptome of S. exigua. Expression profiles revealed that two desaturase ( SexiDes5 and SexiDes11) and three fatty acyl reductase ( SexiFAR2, 3, and 9) genes had PG-specific expression, and phylogenetic analysis demonstrated that they clustered with genes known to be involved in pheromone synthesis in other moth species. Our results provide crucial background information that could facilitate the elucidation of sex pheromone biosynthesis pathway of S. exigua as well as other Spodoptera species and help identify potential targets for disrupting sexual communication in S. exigua for developing novel environment-friendly pesticides. [ABSTRACT FROM AUTHOR]

Background The first-in-class antibody-drug conjugate TAK-264 (formerly MLN0264) consists of an antibody targeting guanylyl cyclase C (GCC) conjugated to monomethyl auristatin E (MMAE) via a peptide linker. This phase II study evaluated the efficacy and safety of TAK-264 in patients with adenocarcinoma of the stomach or gastroesophageal junction expressing GCC, who had progressed on ≥1 line of prior therapy. Methods This study used a two-stage design, with an interim analysis conducted after stage I to determine whether to continue to stage II or discontinue on the grounds of futility. Adult patients with gastric and gastroesophageal junction adenocarcinoma expressing low, intermediate, or high GCC levels received TAK-264 1.8 mg/kg as a 30-min intravenous infusion once every 21 days, for up to 1 year. The primary endpoint was objective response rate. Radiographic assessments of tumor burden were performed every 2 cycles (6 weeks). Results A total of 38 patients participated in the study. Patients received a median of 2 (range 1-14) cycles; 8 (21%) received at least 6 cycles. The most common adverse events were nausea (53%), fatigue (32%), and decreased appetite (29%). Grade ≥3 events including anemia, diarrhea, and neutropenia were seen in 14 (37%) patients. Systemic exposure to TAK-264 was maintained throughout each treatment cycle. Two patients (6%) with intermediate GCC expression had objective responses. Conclusions TAK-264 demonstrated a manageable safety profile in this patient population. The stage I interim analysis did not support continuation to stage II of the study. [ABSTRACT FROM AUTHOR]

Background: As our population ages, neurogenic claudication (NC) from central canal stenosis of the lumbar spine is becoming an increasingly common condition. Studies have been undertaken to assess the efficacy of caudal, interlaminar, or unilateral transforaminal epidural injections, but bilateral transforaminal epidural injections (BTESIs) have not been evaluated to date.Objective: To assess the therapeutic value and long-term effects of fluoroscope-guided BTESIs in patients with NC from degenerative lumbar spinal stenosis (DLSS) of the central spinal canal.Design: Case series.Setting: Single institution spine clinic.Patients: Twenty-six adults between the ages of 40 and 90 years with a diagnosis of DLSS and a history of subacute or chronic NC.Methods/interventions: Patients meeting inclusion criteria received fluoroscope-guided BTESI of local anesthetic and steroid at the level immediately below the most stenotic level. Patient self-reported pain level, activity level, and overall satisfaction were recorded by telephone interview at 1, 3, and 6 months after injection by an independent observer.Main Outcome Measures: Pain score and Swiss Spinal Stenosis score at baseline, 1, 3, and 6 months.Results: Of the 22 participants eligible for analysis, 20, 19, and 18 had follow-up data available at 1, 3, and 6 months, respectively. Reduction in numeric pain scale score of at least 50% was noted in 30% of participants at 1 month, 53% at 3 months, and 44% at 6 months. Swiss Spinal Stenosis subscale scores indicated a significant reduction in the proportion of participants reporting the presence of severe pain in the back, buttocks, and legs (particularly the back or buttocks) at 1, 3, and 6 months of follow-up compared with baseline (P < .05). The proportion of participants reporting severe weakness in the legs or feet also decreased after injection and was statistically significant at 3 months of follow-up (P = .04).Conclusions: Fluoroscope-guided BTESI was moderately effective in reducing pain, improving function, and achieving patient satisfaction in patients with NC from DLSS at the central spinal canal in this clinical case series.Level Of Evidence: IV. [ABSTRACT FROM AUTHOR]

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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]

Although the general pathway of sex pheromone synthesis in moth species has been established, the molecular mechanisms remain poorly understood. The common cutworm Spodoptera litura is an important agricultural pest worldwide and causes huge economic losses annually. The female sex pheromone of S. litura comprises Z9,E11-14:OAc, Z9,E12-14:OAc, Z9-14:OAc, and E11-14:OAc. By sequencing and analyzing the transcriptomic data of the sex pheromone glands, we identified 94 candidate genes related to pheromone biosynthesis (55 genes) or chemoreception (39 genes). Gene expression patterns and phylogenetic analysis revealed that two desaturase genes (SlitDes5 and SlitDes11) and one fatty acyl reductase gene (SlitFAR3) showed pheromone gland (PG) biased or specific expression, and clustered with genes known to be involved in pheromone synthesis in other moth species. Furthermore, 4 chemoreception related genes (SlitOBP6, SlitOBP11, SlitCSP3, and SlitCSP14) also showed higher expression in the PG, and could be additional candidate genes involved in sex pheromone transport. This study provides the first solid background information that should facilitate further elucidation of sex pheromone biosynthesis and transport, and indicates potential targets to disrupt sexual communication in S. litura for a novel pest management strategy. [ABSTRACT FROM AUTHOR]

Genetic methods can complement epidemiological surveys and clinical registries in determining prevalence of monogenic autosomal recessive diseases. Several large population-based genetic databases, such as the NHLBI GO Exome Sequencing Project, are now publically available. By assuming Hardy-Weinberg equilibrium, the frequency of individuals homozygous in the general population for a particular pathogenic allele can be directly calculated from a sample of chromosomes where some harbor the pathogenic allele. Further assuming that the penetrance of the pathogenic allele(s) is known, the prevalence of recessive phenotypes can be determined. Such work can inform public health efforts for rare recessive diseases. A Bayesian estimation procedure has yet to be applied to the problem of estimating disease prevalence from large population-based genetic data. A Bayesian framework is developed to derive the posterior probability density of monogenic, autosomal recessive phenotypes. Explicit equations are presented for the credible intervals of these disease prevalence estimates. A primary impediment to performing accurate disease prevalence calculations is the determination of truly pathogenic alleles. This issue is discussed, but in many instances remains a significant barrier to investigations solely reliant on statistical interrogation-functional studies can provide important information for solidifying evidence of variant pathogenicity. We also discuss several challenges to these efforts, including the population structure in the sample of chromosomes, the treatment of allelic heterogeneity, and reduced penetrance of pathogenic variants. To illustrate the application of these methods, we utilized recently published genetic data collected on a large sample from the Schmiedeleut Hutterites. We estimate prevalence and calculate 95 % credible intervals for 13 autosomal recessive diseases using these data. In addition, the Bayesian estimation procedure is applied to data from a central European study of hereditary fructose intolerance. The methods described herein show a viable path to robustly estimating both the expected prevalence of autosomal recessive phenotypes and corresponding credible intervals using population-based genetic databases that have recently become available. As these genetic databases increase in number and size with the advent of cost-effective next-generation sequencing, we anticipate that these methods and approaches may be helpful in recessive disease prevalence calculations, potentially impacting public health management, health economic analyses, and treatment of rare diseases. [ABSTRACT FROM AUTHOR]