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There is an urgent need for animal models of coronavirus disease 2019 to study immunopathogenesis and test therapeutic intervenes. In this study, we showed that NOD/SCID IL2rg

The study aimed to identify BMI-related lipids and to explore the role of lipids linking BMI and gestational diabetes mellitus (GDM).Plasma lipidome, height, and weight were measured in early pregnancy among 1008 women. Pearson correlation analyses and least absolute shrinkage and selection operator regression (LASSO) were performed to identify BMI-associated lipids. Based on these lipids, a lipid score was created using LASSO, and its association with GDM risk was evaluated by conditional logistic regression. The causal relationships between BMI and lipids were tested by Mendelian randomization analysis with genotyping data. Mediation analysis was conducted to evaluate the mediating effect of lipids on the association of BMI with GDM.Of 366 measured lipids, BMI was correlated with 28 lipids, which mainly belong to glycerophospholipids and glycerolipids. A total of 10 lipid species were associated with BMI, and a lipid score was established. A causal relationship between BMI and lysophosphatidylcholine 14:0 was observed. The lipid score was associated with a 1.69-fold increased risk of GDM per 1-point increment (95% CI: 1.33-2.15). Furthermore, BMI-associated lipids might explain 66.4% of the relationship between BMI and GDM.Higher BMI in early pregnancy was associated with altered lipid metabolism that may contribute to the increased risk of GDM.

Cadmium (Cd) is a widespread heavy metal pollutant in the environment that damages human health. In this study, the bioaccessibility and bioavailability of Cd in different Cd-contaminated rice (low pollution level cadmium rice (Rice-L, 0.111 mg/kg), medium pollution level cadmium rice (Rice-M, 0.400 mg/kg), and high pollution level cadmium rice (Rice-H, 0.655 mg/kg)) were estimated and determined by an in vitro digestion model Rijksinstituut voor volksgezondheiden milieu (RIVM), Caco-2 cell model, and mouse model. The results indicated that Cd in the oral cavity (15.65-28.28%) displayed the lowest bioaccessibility comparing with small intestine (90.04-94.73%) and the stomach (99.30-100.70%) in vitro after cooking. In addition, the results showed that the bioaccessibility of Cd in CdCl2 , CdCl2 +normal rice (Rice-N), Rice-H, Rice-M, Rice-L group were 99.29%, 92.57%, 90.04%, 94.73%, and 91.11%, respectively; the in vitro bioavailability of Cd in CdCl2 , CdCl2 +Rice-N, Rice-H, Rice-M, and Rice-L group were 27.50%, 20.78%, 21.90%, 26.90%, 36.46%, respectively, we found that the group of CdCl2 is significantly higher than CdCl2 +Rice-N and Rice-H (p

Background Among various cooking methods, steaming is favored by many because it can cause less damage to nutrient components in muscle, retain the inherent food flavor, and reduce the generation of harmful substances. Steaming conditions are closely related to fish flavor, fat and protein oxidation, and digestibility. Results The black carp steamed for 4 to 14 min was studied in this article based on sensory assessment, electronic tongue, free amino acids, adenosine triphosphate (ATP)-related compounds, total nitrogen and non-protein nitrogen to explore the effect of steaming time on the taste substances and protein degradation of pickled black carp. The experimental result showed that the meat steamed within 8 min tasted better, showing high tastiness. The sensory assessment score increased significantly to the maximum value of 82.33 at 6 min. The content of umami and sweet amino acids increased significantly to the maximum value of 1.6801 g kg-1 at 6 min. In the meantime, the IMP (inosine monophosphate) content was 1.9128 g kg-1 , with its taste activity value (TAV) reaching 7.65, which proved that IMP affected the taste most. Furthermore, the total nitrogen content was 30.77 g kg-1 , which meant protein degraded a great deal. Based on equivalent umami concentration (EUC) and its TAV, the meat tasted best at 6-8 min. The longer the steaming time, the faster the protein degradation and the more the flavor precursors. Conclusion The black carp pickled products (with a weight of 20 g, with the size of 3 cm × 3 cm × 2 cm) is suggested to be steamed for 6 to 8 min. This conclusion provides a theoretical basis for its better taste quality. © 2020 Society of Chemical Industry.

To better inform the next clinical trials of vascular disrupting agent combretastatin-A4-phosphate (CA4P) in patients with hepatic malignancies, this preclinical study aimed at evaluating CA4P therapeutic efficacy in rats with primary hepatocellular carcinomas (HCCs) of a full spectrum of differentiation and vascularity by magnetic resonance imaging (MRI), microangiography and histopathology. Ninety-six HCCs were raised in 25 rats by diethylnitrosamine gavage. Tumor growth was monitored by T2-/T1-weighted-MRI (T2WI, T1WI) using a 3.0 T scanner. Early vascular response and later intratumoral necrosis were detected by dynamic-contrast-enhanced (DCE) MRI and diffusion-weighted-imaging (DWI) before, 1 and 12 hr after CA4P iv-administration. In vivo MRI-findings were validated by postmortem-techniques. Multi-parametric MRI revealed rapid CA4P-induced tumor vascular shutdown within 1 hr, followed by variable intratumoral necrosis at 12 hr. Tumor volumes decreased by 10% at 1 hr (p

Quantile residual lifetime models are often of concern in survival analysis, especially when studying a chronic or irreversible disease like dementia. In the past several decades residual life models have been studied extensively with right-censored survival data. However these methods are not suitable to analyze the length-biased and right-censored data from the prevalent cohort sampling. In this article we propose nonparametric and semiparametric model-based procedures to estimate the quantile residual lifetime with censored length-biased data. Two test statistics are established for comparing the quantile residual lifetimes of two groups, evaluated, respectively, on ratio and difference in terms of type I error probabilities and powers. Some simulations are conducted to compare the proposed method with existing approaches. Real dementia data from the National Alzheimer's Coordinating Center are used to illustrate the proposed estimation methods by estimating the quantile residual lifetimes of the dementia patients. The Canadian Journal of Statistics 45: 220–250; 2017 © 2017 Statistical Society of Canada

Conventional thermosets consisting of polymer networks with robust and irreversible chemical linkages are incapable of reshaping or reprocessing once formed. In contrast, reversible non-covalent crosslinks can impart structurally flexible and reconfigurable feature to the networks, but at the expense of certain mechanical strength. The integration of fixed covalent bonds and noncovalent bonds into these materials can usually attain enhanced mechanical properties and meanwhile provide dynamic and adaptable functions, such as responsive and healing ability to external stimuli. Here a double-cross-linked frustrated Lewis pair network (FLPN) is developed through a specific three-component reaction among triarylborane, triarylphosphine, and CO2 , which is composed of permanent chemical crosslinks and dynamic CO2 gas-bridged connections. The amount of CO2 added can regulate the density of supramolecular node in such FLPN, so as to control the strength and toughness of the gel material. Moreover, the broken gel can be rapidly healed by CO2 stimulus through the reconstruction of dynamic covalent network. This study will inspire a new way to create gas-based smart materials by incorporating frustrated Lewis pair chemistry into traditional gel system.

The world‐wide spreading of coronavirus disease (COVID‐19) has greatly shaken human society, thus effective and fast‐speed methods of non‐daily‐life‐disturbance sterilization have become extremely significant. In this work, by fully benefitting from high‐quality AlN template (with threading dislocation density as low as ≈6×108 cm−2) as well as outstanding deep ultraviolet (UVC‐less than 280 nm) light‐emitting diodes (LEDs) structure design and epitaxy optimization, high power UVC LEDs and ultra‐high‐power sterilization irradiation source are achieved. Moreover, for the first time, a result in which a fast and complete elimination of SARS‐CoV‐2 (the virus causes COVID‐19) within only 1 s is achieved by the nearly whole industry‐chain‐covered product. These results advance the promising potential in UVC‐LED disinfection particularly in the shadow of COVID‐19., The complete elimination of SARS‐CoV‐2 within 1 s by a high‐power UVC light source is demonstrated. Such an effective sterilization benefits from the well‐crystallized AlN on NPSS and the high‐power UV light source with a typical output power of 2 W at an emission wavelength of 275 nm.

Methamphetamine (METH), an illicit drug, is widely abused in many parts of the world. Mounting evidence shows that METH exposure contributes to neurotoxicity, particularly for the monoaminergic neurons. However, to date, only a few studies have tried to unravel the mechanisms involved in METH-induced non-monoaminergic neural damage. Therefore, in the present study, we tried to explore the mechanisms for METH-induced neural damage in cortical neurons. Our results showed that METH significantly increased intracellular [Ca(2) (+) ]i in Ca(2) (+) -containing solution rather than Ca(2) (+) -free solution. Moreover, METH also upregulated calmodulin (CaM) expression and activated CaM-dependent protein kinase II (CaMKII). Significantly, METH-induced neural damage can be partially retarded by CaM antagonist W7 as well as CaMKII blocker KN93. In addition, L-type Ca(2) (+) channel was also proved to be involved in METH-induced cell damage, as nifedipine, the L-type Ca(2) (+) channel-specific inhibitor, markedly attenuated METH-induced neural damage. Collectively, our results suggest that Ca(2) (+) -CaM-CaMKII is involved in METH-mediated neurotoxicity, and it might suggest a potential target for the development of therapeutic strategies for METH abuse. Copyright © 2016 John Wiley & Sons, Ltd.

The aim of this study was to investigate the effects of verapamil on the pharmacokinetics of pristimerin in rats. A sensitive and reliable LC-MS/MS method was developed and applied for the determination of pristimerin in rat plasma. The pharmacokinetics of orally administered pristimerin with and without verapamil pretreatment was investigated. The results indicated that, when the rats were pretreated with verapamil, the peak concentration of pristimerin increased from 189.13 to 277.53 ng/mL (46.7%), and the AUC0-t increased by approximately 82.0%. Additionally, the effects of verapamil on the absorption and metabolic stability of pristimerin were investigated using the Caco-2 cell transwell model and rat liver microsomes. A markedly higher transport of pristimerin across the Caco-2 cells was observed in the basolateral-to-apical direction and was abrogated in the presence of the P-gp inhibitor, verapamil. These results indicated that P-gp might be involved in the absorption of pristimerin. Of note, the metabolic half-life of pristimerin was prolonged by the pretreatment with verapamil. In conclusion, verapamil could affect the pharmacokinetics of pristimerin, and it might work through increasing the absorption of pristimerin by inhibiting P-gp, or through slowing down the metabolism of pristimerin in the rat liver. Copyright © 2015 John Wiley & Sons, Ltd.

Plants and their extracts have been used especially in China for more than ten centuries for preventing and treating disease. However, there are only few reports describing their use in animal cell culture and tissue transplantation. In this study, onion epithelial membranes (OEM) is used as scaffolds to support cultures of a variety of cells such as fibroblasts and epithelial cells notably; they maintain the phenotypic characteristics of corneal epithelial cells. This improvement includes preservation of the proliferative potential and stemness of rabbit corneal epithelial cells (RCECs). Such an outcome suggests that this cost-effective technology warrants further evaluation to determine if OEM is a viable candidate for use as scaffolds in corneal epithelial transplantation surgery. To test this possibility, rabbit corneal epithelial cells expanded on OEM are transplanted to treat corneal epithelial defects in limbal stem cell deficient rabbits. This procedure is successful because it shortens the time required for wound healing to restore losses in corneal epithelial integrity, and forms a more compact and stratified epithelium framework than the untreated group. Ultimately, should they be proven to be effective in other relevant animal model systems, their usefulness for treating wounds in a clinical setting warrants consideration.

Microglial activation is closely related to the pathogenesis of neurodegenerative diseases by producing proinflammatory cytokines. Perfluorooctane sulfonic acid (PFOS), known as an emerging persistent organic pollutant, is reported to disturb human immune homeostasis; however, whether it affects cytokine production or the immune response in the central nervous system remains unclear. The present study was aimed to explore whether PFOS contributed to inflammatory action and to investigate the corresponding mechanisms in BV2 microglia. PFOS-mediated morphologic changes, cytokine responses and signaling events were examined by light microscopy, real-time polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot assays. Our results indicated that PFOS increased BV2 cells activation and simultaneously increased tumor necrosis factor alpha and interleukin-6 expression. In addition, the c-Jun N-terminal protein kinase inhibitor (SP600125), as well as ERK1/2 blocker (PD98059), transcriptionally at least, displayed anti-inflammatory properties on PFOS-elicited cytokine responses. Moreover, the inflammatory transcription factor NF-κB was specifically activated by PFOS as well. These results, taken together, suggested that PFOS exerts its functional effects on the response of microglial cell activation via, in part, the c-Jun N-terminal protein kinase, ERK and NF-κB signaling pathways with its subsequent influence on proinflammatory action. Copyright © 2015 John Wiley & Sons, Ltd.

Aim To investigate processes at the end of life for patients who died in a subacute evaluation and management facility for older people. Methods A retrospective chart audit for patients (n = 55) who died in the previous 2 years was undertaken, recording a number of significant variables. Results Despite diagnosis of comorbid medical conditions, most participants were admitted for improved functioning or assessment for alternative accommodation. Consistent with this focus, the key contact person was most often an allied health team member. Not For Resuscitation order and/or power of attorney documents on admission were uncommon (

Two hybrids based on 1,8-disubstituted carbazole, 1,8-OXDCz and 1,8-mBICz, have been designed and synthesized through a facile process. The incorporation of oxadiazole or N-phenylbenzimidazole moieties at the 1,8-positions of carbazole greatly improves its morphological stability, giving glass transition temperatures (T(g)) as high as 138 and 154 °C, respectively. Blue phosphorescent organic light-emitting devices (PhOLEDs) with 1,8-mBICz exhibit almost the same performance as a similarly structured device based on the mCP host, and green PhOLEDs employing the new host material 1,8-OXDCz exhibit an ideal turn-on voltage (2.5 V at 1.58 cd m(-2)), a maximum current efficiency (η(c,max)) of 73.9 cd A(-1), and a power efficiency (η(p,max)) of 89.7 lm W(-1). These results are among the best performances of [Ir(ppy)(3)]-based devices with simple device configurations.

BACKGROUND: Ribonucleotide reductase M1 (RRM1) is an important molecule in different types of cancer. The objective of this study was to evaluate the predictive roles of RRM1 in the survival of patients with resectable pancreatic adenocarcinoma who received treatment with gemcitabine or nongemcitabine adjuvant therapy. METHODS: In total, 122 patients underwent tumor resection for pancreatic adenocarcinoma at the authors' institution from October 1999 to December 2007. Total RNA was isolated from microdissected, paraffin-embedded tumors. RRM1 expression levels were measured using quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) and were dichotomized using recursive partitioning analysis. The Kaplan-Meier method was used to estimate overall survival and progression-free survival, and the predictive value of RRM1 expression on survival was examined using Cox proportional hazards regression. RESULTS: RRM1 expression did not have significant prognostic value in the entire cohort regarding overall survival (P = .2) or progression-free survival (P = .7). In the subgroup of 44 patients who received adjuvant gemcitabine, patients who had low RRM1 expression had longer overall survival (median, 47.8 months vs 14.1 months; P = .005) and a trend toward longer progression-free survival (median not reached vs 12.9 months; P = .06). In contrast, in the subgroup of 35 patients who received nongemcitabine adjuvant therapy, patients who had high RRM1 expression had significantly longer overall survival (median, 41.9 months vs 19.8 months; P = .01) and progression-free survival (median, 70.0 months vs 11.8 months; P = .04). These results were confirmed in Cox proportional hazards multivariable analysis. CONCLUSIONS: In patients with resectable pancreatic adenocarcinoma, low RRM1 expression in the tumor predicted an overall survival benefit of adjuvant gemcitabine; and high RRM1 expression predicted the survival benefit of nongemcitabine adjuvant therapy. Cancer 2013. © 2012 American Cancer Society.

The use of small interfering RNA (siRNA) in cancer treatment has been limited by the lack of effective systemic delivery methods. Although synthetic polycations have been widely explored in siRNA delivery, polycation/siRNA polyplexes often suffer from insufficient stability in vivo. Here, rationally designed siRNA delivery systems that meet the requirements for systemic siRNA delivery to distant tumors are reported. The hypothesis that modular design of delivery systems based on poly(amido amine)s that combine fluorination for systemic stability with bioreducibility for easy intracellular siRNA release, and PEGylation for improved safety and colloidal stability will overcome problems with contradicting siRNA delivery demands is tested. PEGylated, fluorinated, and bioreducible copolymers (PEG-PCD-F) with different degree of fluorination are thus synthesized. The fluorinated copolymers readily formed polyplexes with siRNA and achieved greatly improved gene silencing efficacy in multiple cell lines in vitro when compared with nonfluorinated controls. The results show fluorination-induced enhancement of stability, cellular uptake, and endosomal escape of the polyplexes, while exhibiting efficient siRNA release in reducing intracellular environment. PEG-PCD-F polyplexes with siRNA against Bcl2 inhibit breast tumor growth following systemic intravenous administration. The results provide strong evidence of successful combination of bioreducibility with fluorination and PEGylation to achieve systemic siRNA polyplex delivery.

Fault diagnosis is crucial in monitoring industrial processes. Faults con be often detected from residuals generated from the system model. For systems with known models, residuals can be readily generated. However, for systems with unknown models, neural networks can be used to model the system. For small or incipient faults, it is difficult to detect faults directly from the residuals. The asymptotic local approach, which transforms the fault diagnosis problem into one that detects statistical changes in a random variable, is proposed here. The proposed scheme is illustrated by a simulation example, and comparison with faults obtained directly from the residuals is also made.

Optimal conditions are developed for bis- and mono-iodination of substrates (I) in order to get modified structures of the chemically important boron scaffold.

In this paper we propose a new method for the measurement of the relative group delay of WDM components, based on photonic microwave technique using a low frequency (below 1.3 GHz) scalar network analyzer. Experimental results demonstrate that this technique has the advantages of low cost, simplicity, and high accuracy (less than ±1 ps). © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 346–348, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10602

We present and demonstrate experimentally a new method for measuring the polarization mode dispersion (PMD) of chirped fiber Bragg gratings. The technique can also be used to measure chromatic dispersion (CD) more accurately by eliminating the influence of PMD. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 41: 1–2, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20026