Abstract Idiopathic inflammatory myopathy, abbreviated as myositis, is a heterogeneous disease characterized by proximal muscle involvement and chronic inflammation, primarily affecting the lungs. The aim of this study was to establish a stable Idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD) mouse model and evaluate the effects of zanubrutinib on IIM-ILD. We induced an IIM lung involvement model in balb/c mice through intramuscular injection of skeletal muscle homogenate and intraperitoneal injection of pertussis toxin. We observed that the combination of skeletal muscle protein and pertussis toxin in balb/c mice could establish a stable IIM lung involvement model, characterized by muscle inflammation and pulmonary interstitial changes similar to clinical pathology. Zanubrutinib alleviated IIM and ILD, and its anti-inflammatory properties were demonstrated by a reduction in inflammatory cells and inflammatory factors in bronchoalveolar lavage fluid and bronchial inflammation. Its anti-inflammatory and anti-fibrotic effects were mainly achieved through the inhibition of BTK and NF-κB phosphorylation. This study established a stable IIM-ILD animal model and demonstrated for the first time that the BTK inhibitor Zanubrutinib effectively attenuates experimental IIM-ILD in this model.
Quantum Key Distribution (QKD) is considered the most immediate application to be widely implemented amongst a variety of potential quantum technologies. QKD enables sharing secret keys between distant users, using photons as information carriers. An ongoing endeavour is to implement these protocols in practice in a robust, and compact manner so as to be efficiently deployable in a range of real-world scenarios. Single Photon Sources (SPS) in solid-state materials are prime candidates in this respect. Here, we demonstrate a room temperature, discrete-variable quantum key distribution system using a bright single photon source in hexagonal-boron nitride, operating in free-space. Employing an easily interchangeable photon source system, we have generated keys with one million bits length, and demonstrated a secret key of approximately 70,000 bits, at a quantum bit error rate of 6%, with $\varepsilon$-security of $10^{-10}$. Our work demonstrates the first proof of concept finite-key BB84 QKD system realised with hBN defects.
Deglycosylated azithromycin (Deg-AZM), a new transgelin agonist with positive therapeutic effects on slow transit constipation, has been approved for clinical trials in 2024. This work investigated the drug metabolism and transport of Deg-AZM to provide research data for further development of Deg-AZM. A combination of UPLC-QTOF-MS was used to obtain metabolite spectra of Deg-AZM in plasma, urine, feces and bile. Caco-2 cells was used to investigate the permeability of Deg-AZM and whether it is a potential substrate of the efflux transporter P-glycoprotein. Human liver microsome phenotyping assays with chemical inhibition and recombinant CYPs phenotyping assays were used to investigate the CYP450 enzyme phenotype involved in Deg-AZM metabolism in vitro. A HLM inhibition reaction system was established to evaluate the inhibitory effect of Deg-AZM on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. The mRNA expression of human primary hepatocytes incubated with Deg-AZM or not was evaluate the induction of Deg-AZM on CYP1A2, CYP2B6, and CYP3A4. 44 metabolites of Deg-AZM were identified in rat urine, feces, bile, and plasma, the metabolic pathways included demethylation, monohydroxylation, dihydroxylation, dehydroxidation, hydroreduction, hydrolysis, methylation, glucuronidation and the combination of different metabolic pathways. Deg-AZM was a low permeability drug in the intestine and a potential substrate of the efflux transporter P-glycoprotein. CYP3A4 was the major CYP isoform responsible for Deg-AZM metabolism. Deg-AZM showed moderate inhibition with CYP2B6 and CYP2D6. Data in three batches of human primary hepatocytes disclosed induction potential of Deg-AZM on CYP2B6 and CYP3A4. The in vivo metabolic pathway of Deg-AZM and in vitro possibility of drug interaction for Deg-AZM with CYP enzymes and drug transporter were fully investigated. It was suggested that dose adjustments may be warranted depending on the potency of the corresponding modulators in clinical.
An experimental study was conducted in an indoor soil tank to examine to nitrogen infiltration and movement through unsaturated soil in topsoil layer of riparian zone.The timing of seepage flow from the tank and the seepage sequence at different sampling points were monitored.The variation of nitrogen concentrations(e.g.,total nitrogen TN and ammonia NH+4-N) was also observed.Results show that the vertical velocity of percolation water is larger than the horizontal one during infiltration into the unsaturated topsoil layer of riparian zone.In the process from dry-to-wet and wet-to-dry,the TN and NH+4-N concentrations first has a sharp increase and then gradually decrease until reaching a stable state.This is true for every monitoring point.In addition,the nitrogen retention capacity in the topsoil layer of riparian zone is high under unsaturated conditions.Along the 1.08m long slope and 11 hours after the experiment began,the TN and NH+4-N concentrations at points 12 cm below the surface reduce by 74.23% and 68.02%,respectively.
// Huijuan Liu 1, 2, * , Qin Tian 1, * , Xiaoyu Ai 1, * , Yuan Qin 1 , Zhanhong Cui 1 , Meng Li 1 , Jiahuan Yang 1 , Denghui Zhai 1 , Yanrong Liu 3 , Shuang Chen 3 , Jing Meng 1 , Tao Sun 1, 3 , Honggang Zhou 1, 3 and Cheng Yang 1, 3 1 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, College of Life Sciences, Nankai University, Tianjin, China 2 College of Life Sciences, Nankai University, Tianjin, China 3 Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China * These authors have contributed equally to this work Correspondence to: Cheng Yang, email: cyang66_2001@yahoo.com Honggang Zhou, email: honggang.zhou@vip.126.com Tao Sun, email: sunrockmia@hotmial.com Keywords: DHA; AIT; CXCR3; PI3K; NF-κB Received: September 19, 2017 Accepted: November 13, 2017 Published: December 01, 2017 ABSTRACT Dihydroartemisinin (DHA) is the first generation of naturally occurring artemisinin derivatives with antimalarial activity. Recent research showed that this drug also features immunosuppressive and anti-inflammatory properties. Autoimmune thyroiditis (AIT) is a common organ-specific autoimmune disease with no available effective drug treatment. In this study, we investigated effects of DHA on AIT in vitro and in vivo . Results showed that DHA can visibly reduce antithyroglobulin antibody and thyroid peroxidase antibody levels and regulate T helper cells (Th) 1/Th2 imbalance of experimental AIT mice. DHA also dose-dependently suppressed proliferation of lymphocytes induced by lipopolysaccharide and concanavalin A. DHA inhibited binding of C-X-C chemokine ligand 10 (CXCL10) and its receptor (C–X–C motif) receptor 3 (CXCR3), thus inhibiting calcium flow. DHA can also reduce expression levels of PI3-kinase (PI3K), p-PI3K, protein kinase B (AKT), p-AKT, nuclear factor (NF)-κB/p65, and p-NF-κB/p65. In conclusion, DHA may serve as treatment drug for AIT by inhibiting the CXCR3/PI3K/AKT/NF-kB signaling pathway.
In addition to being a physiological protective barrier, the gastrointestinal mucosal membrane is also a primary obstacle that hinders the oral absorption of many therapeutic compounds, especially drugs with a poor permeability. In order to resolve this impasse, we have designed multifunctional nanomicelles based on the acetylcysteine functionalized chitosan-vitamin E succinate copolymer (CS-VES-NAC, CVN), which exhibit marked bioadhesion, possess the ability to penetrate mucus, and enhance the oral absorption of a hydrophobic drug with a poor penetrative profile, paclitaxel. The intestinal absorption (Ka = 0.38 ± 0.04 min(-1), Papp = 0.059 cm · min(-1)) of CVN nanomicelles was greatly improved (4.5-fold) in comparison with paclitaxel solution, and CLSM (confocal laser scanning microscope) pictures also showed not only enhanced adhesion to the intestinal surface but improved accumulation within intestinal villi. The in vivo pharmacokinetics indicated that the AUC0-t (586.37 ng/mL · h) of CVN nanomicelles was markedly enhanced compared with PTX solution. In summary, the novel multifunctional CVN nanomicelles appear to be a promising nanocarrier for insoluble and poorly permeable drugs due to their high bioadhesion and permeation-enhancing capability.
To improve the water quality of Wangyu River, which is the important diversion channel for Water Transfer from Yangtze River to Lake Taihu, a ecological spur-dike was constructed in Wangyu River, This project combined the traditional water conservancy engineering with the biofilm technology, which can not only slow velocity and settle down sediment but also degrade organic pollutants and absorption nutrients in river water by organisms in biofilm. After 39 days of the construction, biofilm characters on the surface of globular biofilter were performed five times to analyze the changing process of microbial community. In addition, 3 sites of water samples were also observed before and behind the spur-dike, and in the background of Wangyu River. it was found that spur-dike has good effect on water purification. Results show that 70 taxa of attaching organism were identified on the biofilter, and major divisions were Bacillariopyta 37, Chlorophyta 20 and Cyanophyta 7. Compared with the background values, the purification efficiency of SS, TP, TN and COD Mn were at the range of 5.1%–61.2%, 16.4%–57.2%, 8.2%–17.7%, 1.6%–34.5%, respectively. This study provided support for the development of river ecosystem restoration projects of in the future.
The aim of the present study is to investigate whether the use of the biorelevant concentration of conventional surfactants as an alternative medium to simulated fasted state intestinal fluid for drugs with different acid–base properties is feasible.
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