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Objective: To observe the effects of Zhuang Gu Zhi Tong Formula (ZGZTF) on antagonist SOST in canonical Wnt/β-catenin signaling pathway in osteoporosis. Methods: We analyzed the differential genes of patients with osteoporosis and normal subjects from the GEO database and then found SOST with specific expression. We analyzed SOST as an antagonist of the Wnt signaling pathway by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then we studied the effect of ZGZTF on SOST in Wnt signaling pathway. Osteoporosis model was induced by ovariectomy (OVX) in 8-week-old female Sprague–Dawley (SD) rats. After 12 weeks of treatment with ZGZTF by intragastric administration, the rats were put to death in batch. The changes of alkaline phosphatase (ALP), bone gla protein (BGP) and estradiol (E2) in serum were determined, and bone mineral density (BMD) and histomorphology of right femur were observed. Biomechanics of lumbar vertebra were measured, and the expression of SOST, Wnt3a, β-catenin, LRP5, Runx2, Osx and their mRNA involving the canonical Wnt/β-catenin signaling pathway were detected by Western blot, RT-PCR and Immunohistochemical analysis. All data were analyzed by SPSS 22.0. Results: Twelve weeks of treatment with ZGZTF could significantly decrease the level of ALP and BGP in serum, increase the BMD of femurs, and improve the biomechanical capability of vertebral body in maximum loading and elastic modulus. Concerning histomorphology, we found ordered arrangement of trabeculae, slightly thinning of trabeculae and none obvious slight fractures in femurs after 12 weeks of treatment with ZGZTF. The expression of LRP5, β-catenin, Runx2 and Osx involved in the canonical Wnt/β-catenin signaling pathway was significantly up-regulated in the presence of ZGZTF, and the expression of SOST in this pathway was down-regulated. Conclusions: These results suggest that ZGZTF may be anti- osteoporosis by down-regulating SOST protein to promote Wnt/β-catenin signaling pathway. Keywords: Zhuang Gu Zhi Tong Formula (ZGZTF), Osteoporosis, SOST, Wnt, LRP5, β-catenin, Runx2, Osx

The paper introduced composition of plough mining system and application of technology of frequency-conversion speed-regulation in plough mining system. The application of technology of frequency-conversion speed-regulation improves efficiency of speed-regulation of driving system, realizes infinite speed-regulation of driving system, reduces vibrational loads of driving system of plough mining system in starting, solves exothermic problem causd by frequent start and commutating of driving motor of plough, and realizes really soft start. The technology improves driving reliability and working safety of plough mining system.

A new 2D manganese(II) coordination polymer, namely [Mn(L)0.5(2,2′-bipy)]n·nH2O (1), has been constructed hydrothermally based on manganese acetate and the mixed ligands including the 5.5′-(benzene)-1,4-diyl)-bis(oxy) diterphthalic acid (H4L) and auxiliary 2,2′-bipyridine (2,2′-bipy). The compound was characterized by elemental analyses, was characterized by elemental analysis, infrared spectrum and single-crystal and powder X-ray diffractions, and thermal analyses. Single-crystal X-ray diffraction analyses revealed that compound 1 crystallize in the triclinic system, space group P-1. The adjacent Mn(II) ions are bridged by µ6-L4− ligands, producing a 2D layer. Magnetic studies for compound 1 demonstrate an antiferromagnetic coupling between the adjacent Mn(II) centers. [ABSTRACT FROM AUTHOR]

Background: Psoralea Fructus (PF) is one of the most frequently applied tonic Chinese herbs with various bioactivities, while recently, the idiosyncratic drug-induced liver injury (IDILI) nature of PF was addressed, and liver injury cases were reported in the clinic. Our previous research indicated that many constituents exerted liver injury property, whereas the pharmacokinetic profile of these compounds between normal and immune stress states is still unclear. Objectives: This study aims to construct a validated method to simultaneously determine eight analytes (including psoralen, isopsoralen, psoralidin, corylin, psoralenoside, isopsoralenoside, bavachin, and neobavaisoflavone) in PF via UPLC-TQ/MS, and to compare their pharmacokinetic properties in normal and LPS-stimulated rats. Materials and Methods: The rats were randomly divided into four groups. The blood samples of different groups were harvested at different time points; the eight analytes were analyzed under UPLC-TQ/MS, and the constructed method was confirmed in terms of specificity, linearity, lower limit of quantitation (LLOQ), precision, accuracy, stability, recovery, and matrix effect. Results: The developed UPLC-TQ/MS method showed good linearity (r = 0.9972–0.9994) and specificity; the recovery and matrix effect were acceptable (ranging from 64.75 ± 1.59% to 104.31 ± 3.38%, and from 87.11 ± 1.91% to 115.45 ± 1.63%, respectively), the intra- and inter-day precision of eight analytes were under 13.42%, the intra- and inter-day accuracy was eligible (92.68%–108.85%), and the analytes were stable under storage conditions. All eight analytes in PFE were rapidly absorbed into the circulation, while the relevant pharmacokinetic parameters (including AUC, MRT, VRT, λ, V, t1/2, Cmax, Tmax, and CL) of these analytes were quite different between the normal and model rats. Conclusion: A sensitive, accurate, and rapid method was successfully established and validated to determine the plasma characteristics of analytes in normal and LPS-primed rats. The pharmacokinetic profile indicated the body states might appreciably impact the pharmacokinetic profile of the bioactive constituents of PF, further inducing liver injury in specific patients. [ABSTRACT FROM AUTHOR]

C26H26N6O9Ni, triclinic, P 1 ‾ $‾{1}$ (no. 2), a = 11.2329(5) Å, b = 11.7535(5) Å, c = 12.1109(7) Å, α = 70.936(5)°, β = 75.684(4)°, γ = 63.266(4)°, V = 1340.13(13) Å3, Z = 2, Rgt(F) = 0.0314, wRref(F2) = 0.0743, T = 290 K. [ABSTRACT FROM AUTHOR]

Abstract A new isolate of canine distemper virus (CDV), named ZJ7, was isolated from lung tissues of a dog suspected with CDV infection using MDCK cells. The ZJ7 isolate induced cytopathogenic effects of syncytia in MDCK cell after six passages. In order to evaluate pathogenesis of ZJ7 strain, three CDV sero-negative dogs were intranasally inoculated with its virus suspension. All infected dogs developed clinical signs of severe bloody diarrhea, conjunctivitis, ocular discharge, nasal discharge and coughing, fever and weight loss at 21 dpi, whereas the mock group infected with DMEM were normal. The results demonstrated that CDV-ZJ7 strain isolated by MDCK cell was virulent, and the nucleotide and amino acid sequences of strain ZJ7 had no change after isolation by MDCK cell when compared with the original virus from the fresh tissues. Molecular and phylogenetic analyses for the nucleocapsid (N), phosphoprotein (P) and receptor binding haemagglutinin (H) gene of the ZJ7 isolate clearly showed it is joins to the Asia 1 group cluster of CDV strains, the predominant genotype in China.

Linking antigen specificity to T cell receptor (TCR) sequences is critical, albeit challenging, to both understanding T cell biology and developing T cell-based therapeutics. Here, we describe in detail tetramer-associated TCR sequencing (TetTCR-Seq), a novel approach to tackling this challenge. TetTCR-Seq is accomplished by multiplexing DNA-barcoded peptide-MHC (pMHC) tetramers, allowing for simultaneous recall of antigen specificity and TCR sequences after single cell sequencing. Additionally, TetTCR-Seq simplifies labor and cuts cost by taking advantage of in vitro transcription and translation (IVTT) to generate peptide libraries and DNA barcodes, in parallel, from the same template. Thus, TetTCR-Seq is a powerful technology capable of quickly and affordably surveying the T cell repertoire for hundreds of antigen specificities in a single experiment., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This paper aims to provide some experimental basis for unveiling the role of PDRG1 (P53 And DNA Damage-Regulated Gene 1) gene silencing in the growth and development of gastric cancer., Methods: PDRG1 levels in gastric cancer tissues and cell lines were measured by Western blotting. Then, gastric cancer BGC-823 cells, divided into Control, PDRG1 siRNA, NC siRNA and PDRG1 siRNA + KU55933 (ATM inhibitor) groups, were used to conduct a series of in vitro experiments including MTT, Flow cytometry, Wound-healing and Transwell assays. Expression of PDRG1 and ATM/p53 pathway-related proteins were determined by Western blot. Eventually, experiment in vivo was carried out to verify the control of PDRG1 on gastric cancer cells after establishing the tumor xenograft model in nude mice., Results: PDRG1 was significantly elevated in gastric cancer tissues and was associated with lower cell differentiation degree, more severe lymph node metastasis and higher tumor stage of gastric cancer patients. The growth of BGC-823 cells were significantly retarded and the cell apoptosis was increased in the PDRG1 siRNA group; besides, cell cycle was arrested in G2/M phase, and the expressions of p-ATM, p53, p21, p-cdc2 and cleaved caspase-3 were up-regulated with the reduced PDRG1. However, KU55933 could reverse the anti-tumor effect of PDRG1 siRNA on BGC-823 cells. The in-vivo experiment confirmed PDRG1 siRNA can inhibit tumor xenograft growth in nude mice., Conclusion: Specific PDRG1 gene silencing may inhibit the growth and metastasis of gastric cancer cells through the activation of ATM/p53 pathway., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

In the present study,non-targeted metabolomics technique was used to screen potentially susceptibility biomarkers in patients with mild liver function abnormalities during long-term use of Chinese herbal compound. According to the inclusion and exclusion criteria,we collected 7 cases of patients with abnormal liver function during the period of complete taking Chinese herbal medicine( 60 days),and 18 cases of patients with normal liver function in re-examination from the reproductive medicine center in our hospital. Ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOF/MS~E) technique combined with Progenesis QI software was used to analyze the differential biomarkers in serum of patients with wild liver function abnormalities and normal liver function. 11 potential biomarkers such as bilirubin,pantothenic acid,hippuric acid,sphingomyelin,palmitic acid,and oleic acid were tentatively identified. Metabolic disorders in patients with herbal-induced mild liver abnormality were mainly related to two pathways: pantothenic acid and coenzyme A biosynthesis and linoleic acid metabolism. It could provide a reference for the early warning of mild liver function abnormalities of patients that may be caused by long-term use of Chinese medicine compound in clinical application,and will lay a foundation for further understanding the endogenous substance changes in different levels of liver injury.

Naoxintong capsule (NXTC) is an oral Chinese preparation produced by modern technology, derived from the classic preparation of Buyang Huanwu decoction which was recorded by WANG Qing-ren (Qing dynasty) in Yilingaicuo Juanxia Tanweilun. NXTC is composed of 16 herbs including insect herbs and some blood circulation herbs, with the effects of supplementing Qi and activating blood circulation, dispersing blood stasis and dredging collaterals. In clinical application, it is mainly used for stroke, cerebral infarction, vascular dementia, ischemic cerebrovascular disease, transient ischemic attack, coronary heart disease, angina pectoris, ischemic cardiomyopathy, diabetic cardiomyopathy, myocardial infarction, chronic heart failure, chronic complications of diabetes, essential hypertension, hyperlipidemia and other cardiovascular and cerebrovascular diseases, and has achieved good therapeutic effect on above diseases or their concurrent diseases. Its clinical efficacy is mainly achieved through the improvement in related links of brain protection, neuroprotection, cardioprotection, hemorheology, et al. Nearly 200 chemical constituents identified in NXTC are important pharmacological basis for its functions. At present, however, most of its pharmacological basic researches are focused on plant herbs, and the three kinds of insect herbs remain to be further studied. The researches on clinical effectiveness are more comprehensive; the safety study of long-term application in real world is ongoing by our team, and its results are yet to be published after finishing the study. Through the systematic and comprehensive combing and elaboration of the research progresses on the chemical compositions, pharmacological action and clinical application of NXTC, it can provide a reference for the in-depth study of this preparation, with a great significance for the quality control, secondary development and internationalization promotion of NXTC., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

To establish HPLC-MS/MS method for simultaneous determination of 14 toxic or active components in Fuzi formula granules, and further analyze the quality consistency of 29 batches of formula granules by considering the cluster analysis (CA), principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) and other chemometrics methods. Phenomenonex Gemini C18 column (4.6 mm×150 mm, 5 μm) was used with 0.1% formic acid solution (A) -acetonitrile (B) as the mobile phase. The mass spectrum was scanned by ESI⁺ multiple reaction monitoring (MRM) mode. The contents of aconitine, mesaconitine, hypaconitine, Indaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconitine, aconine, fuziline, neoline, talatisamine, songorine, higenamine and salsoline were determined. The results showed that 14 compounds had a good linear relationship within their respective concentration range (R²>0.990 0). The limit of quantification was 2.07-7.71 mg·L⁻¹, and the average recovery was 96.07%-102.2%. The content determination results demonstrated that all batches of Fuzi formula granules had very low hypertoxic ingredients and high safety, while the content of active ingredients was greatly different. CA and PCA results showed that there were significant differences in the formula granules between two manufacturers; even though the different batches of samples from the same manufacturer had certain differences, but the difference in manufacturer A was less than that of B. Further PLS-DA showed that the content of cardiotonic substance salsola in the formula granules from manufacturer A was generally higher, while the contents of analgesic and anti-inflammatory substances benzoylmesaconitine and fuziline were generally lower than those in the products from manufacturer B. In conclusion, the safety of Fuzi formula granules was assured well, but the consistency needed to be improved. We recommend that all manufacturers establish strict standard for decoctions in the production process, and form a unified standard method to produce better Fuzi formula granules., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)