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Gout, the most prevalent inflammatory arthritis worldwide, released interleukin-1β (IL-1β) and Cathepsin B inflammatory mediators that constitute the hallmark of the disease. Herein we aimed to investigate whether procyanidin B2 (PCB2), a natural dietary compound, can suppress MSU crystals-stimulated gouty inflammation. Treated with lipopolysaccharide (LPS) plus MSU, both mouse peritoneal macrophages (MPM) and mouse bone marrow-derived macrophages (BMDM) released a large amount of mature IL-1β compared to those treated with MSU or LPS alone, while IL-1β release was blocked by TLR4 and its downstream effector inhibitors. In two mouse models of gout, oral administration of PCB2 suppressed MSU crystals-induced increasing expression of IL-1β, Cathepsin B and NLRP3 in the air pouch skin and paws, accompanied with the downregulation prostaglandin E2 (PGE2) in pouch exudates. Inflammatory immune cell infiltration including macrophages and neutrophils were significantly blocked by PCB2 in air pouch skin and paws of mice gout groups. PCB2 also suppressed the release of IL-1β and Cathepsin B induced by MSU plus LPS in MPM. Our results suggest that the inhibitory effects of PCB2 on NLRP3 inflammasome may alleviate inflammatory response in gout, and this might be a promising anti-inflammatory mechanism of PCB2 against the inflammation in gout. [ABSTRACT FROM AUTHOR]

To ensure the safe and effective application of deep geotechnical engineering, it is necessary to establish a suitable constitutive model of the rocks in thermal environment, including geothermal energy mining, and deep geological treatment of nuclear waste and tunnel fire. A strain-softening damage model of the rocks with defect growth is established based on damage evolution. According to the change in the tangent modulus from the compression phase to the elastic stage, we established a constitutive model reflecting the nonlinearity characteristics of the compression phase. According to the change in the energy conversion, the energy consumption coefficient is introduced to describe the deformation characteristics of the rocks when the residual stress is reached. The specific physical meaning and the calculation method of the energy consumption coefficient are given to correct the shortcomings of the evolution of the damage variable. We then analyzed the relationship between parameters in the constitutive model of the rocks at high temperature and normal temperature. Based on the constitutive model of the rocks at normal temperature, we established a constitutive model reflecting the influence of high temperature. Finally, the established model fit the stress-strain curves of several kinds of the rocks at different temperatures and generated desired results. The established model can be used to describe the stress-strain curve characteristics of the rocks at different temperatures. [ABSTRACT FROM AUTHOR]

Highlights • This study focus on virus elimination from eight potato-valuable cultivars belonging to the Norwegian potato germplasm. • Compare meristem culture, cryotherapy and chemotherapy combined with thermotherapy in the same platform for the first time. • Small RNA HTS was used after virus eradication to confirm virus status of potato virus-free materials. • The results provide a technical platform for establishment of virus-free potato germplasm in Norway. Abstract Potato (Solanum tuberosum L.) is one of the most important crops grown in Norway, and virus-free plants are required for commercial potato production and for preservation of potato germplasm. The present study evaluates three in vitro therapies – meristem culture, cryotherapy, and chemotherapy combined with thermotherapy – to eliminate viruses from eight historically valuable potato cultivars belonging to the Norwegian potato germplasm. Potato virus Y, potato virus M, potato virus X and potato virus S were present in eight selected old potato cultivars due to long-term conservation in open field. Double-antibody sandwich enzyme-linked immunological assay (DAS-ELISA) and biological indicators were the standard tests used to confirm virus infection in our study. Six virus-free plants from four potato cultivars were obtained after meristem culture, and no virus-free potato cultivars were obtained after cryotherapy. Virus-free frequency for eight different potato cultivars after combining chemotherapy with thermotherapy varied from 36.4% to 100%, with single virus elimination rates of between 74.2% and 92.9%. Chemotherapy compared with thermotherapy was the most effective of the three in vitro therapies used in this study. Highly sensitive small RNA high-throughput sequencing (HTS) was used to evaluate the virus status of potato virus-free materials after virus eradication, and no virus was found, which was consistent with the results of DAS-ELISA and biological indicators. Small RNA HTS has been reported for the first time to evaluate the virus status after virus elimination and to control virus-free potato nuclear stocks. [ABSTRACT FROM AUTHOR]

Background: The present study aims to investigate the protective effects of the SOCS1-JAK2-STAT3 signaling pathway on neurons in a rat model of ischemic stroke. Methods: Our study was conducted using an ischemic stroke rat model. After the microglia were extracted, 40 neonatal Sprague-Dawley (SD) rats were assigned into the blank, AG490, model and negative control (NC) groups. The neurological function of all the rats was evaluated. Histopathological changes were observed. qRT-PCR and western blotting were applied to measure the expression of genes and proteins in the SOCS1-JAK2-STAT3 signaling pathway and related to apoptosis. The TUNEL assay was conducted to calculate the cellular morphology and apoptosis of neuronal cells. Cell viability was detected using the MTT assay. In addition, immunoassays were used to measure the content of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) as well as the levels of oxidative stress. Results: Compared with the blank group, the model and NC groups showed higher neurological function scores--the cytoplasm of the neurons were cavitated, the organelles were reduced with unclear margins, some of the neurons were necrotic, and apoptosis was increased. In addition, the NC and model groups exhibited decreased cell viability, lower mRNA and protein expression of SOCS1 SOCS3 and bcl-2 and reduced SOD and GSH levels but higher mRNA and protein expression levels of AK2, STAT3, Bax and caspase-3 as well as increased protein expression of P-JAK2, P-STAT3 and activated caspase-3 (c-caspase-3). Moreover, the MDA levels were up-regulated in the NC and model groups. In contrast, opposing trends were found in the AG490 group compared with the NC and model groups. Conclusion: These data demonstrate that inhibiting the SOCS1-JAK2-STAT3 signaling pathway can reduce the loss of nerve function and apoptosis of neuronal cells, which provides a new target for the clinical treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

The article discusses photoresponsive host-guest functional systems. Topics include photoresponsive rotaxane, catenanes, and pseudorotaxanes; light-responsive mechanical motion powered by photoisomerization; photoresponsive supramolecular polymers and supramolecular interactions in main chain; and photoresponsive host-guest system on surfaces.

A rapid method based on pressurized liquid extraction followed by high-performance liquid chromatography coupled with evaporative light scattering detection was firstly developed for the quantitative analysis of two bioactive triterpenoids (acankoreoside A and acankoreagenin) in the leaves of Schefflera octophylla and Schefflera actinophylla. The analysis was performed on an Agilent Zorbax SB-Aq column (4.6 × 50 mm, 3.5 μm) with gradient elution of 0.1% formic acid and acetonitrile. Calibration curves of two analytes showed good linearity ( R2 > 0.9990) within the tested ranges. This novel method is simple, rapid and accurate, and the results of quantification showed that contents of each investigated compound is significant high in natural S. octophylla (6.36-14.83%), which indicated that natural S. octophylla as potential medicinal resource. Furthermore, hierarchical clustering analysis based on the typical peaks of acankoreoside A and acankoreagenin from the 17 tested samples showed that natural and cultured Schefflera species were in different clusters, which could provide a means of discriminating between Schefflera species from different origins. Thus, acankoreoside A and acankoreagnin could be selected markers for quality control of S. octophylla and S. actinophylla. [ABSTRACT FROM AUTHOR]

For comprehensive utilization of coal gangue and iron ore tailings, XRD, FE-SEM and EDX were used to analyze hydration products and microstructure of autoclaved aerated concrete (AAC) mainly from coal gangue and iron ore tailings. Furthermore, it was studied that the influence of raw materials and the optimal thermal activation temperature of coal gangue to physical and mechanical prosperities. The results show that 600 °C is the optimal calcination temperature AAC with bulk density of 608 kg/m³ and strength of 3.64 MPa, which can reach the requirements of A3.5, B06 level of AAC product regulated by "autoclaved aerated concrete block" GB 11968-2006. There exists ettringite before autoclaved and the main hydration products are tobermorite, C-S-H gel and hibschite, which is globular and botryoidalis. [ABSTRACT FROM AUTHOR]

A high-performance anion-exchange chromatography coupled with diode array detection method was developed for the determination of dencichine in Panax notoginseng and related species. The analysis was performed on an Eprogen Synchropak WAX column (4.6 × 250 mm, 6 μm) with 50 mM NaH2PO4 aqueous solution isocratic elution. The method was validated in terms of linearity, sensitivity, precision, stability, and accuracy. It was found that the calibration curve for dencichine showed good linearity ( R2 = 0.9999) within the test range. The LOD and LOQ were 0.77 and 3.06 ng, respectively. The RSD for intra- and interday repeatability was 0.2 and 0.5%, respectively. The test solution of dencichine is stable at least for three days at room temperature and for seven days at 4°C. The mean recovery of dencichine was 102.0%. The established method was successfully applied to determine dencichine in the raw root of P. nogoginseng, P. ginseng, and P. quinquefolium as well as the steamed root of P. notoginseng. Compared with previous reports, this method is sensitive, selective, and accurate, which is helpful to evaluate the quality of P. notoginseng and related species. [ABSTRACT FROM AUTHOR]

Abstract: The characteristics of core binding factor (CBF) leukemia appear to differ between Chinese and Caucasian patients. In this study, we analyzed the biological and clinical characteristics of 76 Chinese CBF leukemia patients out of 425 newly diagnosed acute myeloid leukemia (AML) patients. The frequency of CBF AML was 17.9%. Patients harboring t(8;21) were predominant in CBF AML. The incidence of c-kit mutation in CBF AML was 28.9%. The N822K mutation appeared to be more prevalent in Chinese CBF AML patients. Multivariate analysis showed that c-kit mutation and high white blood cell count could negatively impact overall survival (OS) (HR=2.74 and 6.24, P =0.007 and 0.022, respectively) but did not affect relapse-free survival (RFS). Kaplan–Meier analysis showed a significant difference in both OS and RFS between wild-type and mutated c-kit patients. Although we had included recently reported prognostic indicators in our analysis, our results demonstrated that only c-kit mutation and high white blood cell count had prognostic impact on Chinese CBF AML patients. [Copyright &y& Elsevier]

NPM1 mutation is the most common molecular abnormality in patients with acute myeloid leukemia (AML), especially normal karyotype AML (NK-AML), and is associated with a favorable prognosis in the absence of concomitant FLT3-ITD. Like other molecular abnormalities such as FLT3-ITD, C/EBPα and c-Kit mutation, NPM1 mutation normally presents as a recurrent molecular abnormality. The NPM1 mutation is generally used as a molecular marker in the prognosis evaluation of a patient with AML. Here, we report a different case. He was first diagnosed with NPM1 mutation-positive acute monocytic leukemia. However, he achieved no remission, but the NPM1 mutation dramatically became negative after induction chemotherapy. Finally, he achieved complete remission after salvage chemotherapy and the NPM1 mutation was still negative. To our knowledge, this is a rare case according to the worldwide published literature. [ABSTRACT FROM AUTHOR]

T(15;17) is the most common chromosomal aberration in patients with acute promyelocytic leukemia (APL), leading to the formation of PML-RARα fusion gene. In a small subset of patients with APL, the RARα gene is fused with different partners. Here, we report a rare APL case with STAT5B-RARα fusion transcript. Cytomorphologic and immunophenotypic analyses showed typical features of APL. However, cytogenetic analysis showed normal karyotype, and interphase fluorescence in situ hybridization (FISH) showed PML-RARα negative. Quantitative RT-PCR also showed PML-RARα negative but STAT5B-RARα positive and sequencing analysis confirmed the result. Molecular markers including FLT3, NPM1, c-Kit and C/EBPα mutation were all negative. To our knowledge, this is the first APL patient with STAT5B-RARα in Chinese population and the fifth patient around the world according to published paper. [ABSTRACT FROM AUTHOR]

Abstract: An approach for rapid optimization of dual-mode gradient high performance liquid chromatography (HPLC) by response surface methodology (RSM) was developed for fast simultaneous separation of hydrophilic and hydrophobic components in Radix et Rhizoma Salviae Miltiorrhizae (Danshen) and its preparations. The aim of this study was to achieve a high throughput RSM optimization using a short ultra-high performance liquid chromatographic (UHPLC) column to simultaneously optimize flow rate and solvent gradient, and then transfer the optimized method to conventional HPLC for routine analytical purposes. The optimization was designed with Box Behnken design (BBD) and the global Derringer''s desirability was used for describing the multicriteria response variables. Sixty-two designed experiments were performed by UHPLC with a short sub-2μm column (2.1mm×50mm, 1.7μm) and a total running time of only 5h. The predicted gradient profile was further transferred to a long UHPLC column (2.1mm×100mm, 1.7μm) and a conventional HPLC columns (2.1mm×100mm, 3.5μm and 4mm×100mm, 5μm, respectively). Compared to the published methods, the newly developed dual-mode gradient is faster and more efficient at simultaneously separating hydrophilic and hydrophobic components in Danshen and its preparations. [Copyright &y& Elsevier]

Abstract: A novel tetranuclear silver(I) heterocyclic cluster, which is of nano-hole structure, based on 1,1′-bis[(2-hydroxybenzylidene)thiocarbonohydrazono-1-ethyl] ferrocene (FcL) has been prepared and structurally characterized by single-crystal X-ray diffractions. In addition, its electrochemical properties are also discussed. The results confirm that the receptor FcL is responsive to Ag+. [Copyright &y& Elsevier]

In this paper, we summarize our recent experimental and theoretical works on observation and control of scroll wave (SW) turbulence. The experiments were conducted in a three-dimensional Belousov–Zhabotinsky reaction-diffusion system with chemical concentration gradients in one dimension. A spatially homogeneous external forcing was used in the experiments as a control; it was realized by illuminating white light on the light sensitive reaction medium. We observed that, in the oscillatory regime of the system, SW can appear automatically in the gradient system, which will be led to spatiotemporal chaos under certain conditions. A suitable periodic forcing may stabilize inherent turbulence of SW. The mechanism of the transition to SW turbulence is due to the phase twist of SW in the presence of chemical gradients, while modulating the phase twist with a proper periodic forcing can delay this transition. Using the FitzHugh–Nagumo model with an external periodic forcing, we confirmed the control mechanism with numerical simulation. Moreover, we also show in the simulation that adding temporal external noise to the system may have the same control effect. During this process, we observed a new state called “intermittent turbulence,” which may undergo a transition into a new type of SW collapse when the noise intensity is further increased. The intermittent state and the collapse could be explained by a random process. [ABSTRACT FROM AUTHOR]

Abstract: Mesenchymal stem cells (MSCs) are known as a population of multi-potential cells able to proliferate and differentiate into multiple mesodermal tissues including bone, cartilage, muscle, ligament, tendon, fat and stroma. In this study human MSCs were successfully isolated from the umbilical cords. The research characteristics of these cells, e.g., morphologic appearance, surface antigens, growth curve, cytogenetic features, cell cycle, differentiation potential and gene expression were investigated. After 2weeks of incubation, fibroblast-like cells appeared to be dominant. During the second passage the cells presented a homogeneous population of spindle fibroblast-like cells. After more than 4months (approximately 26 passages), the cells continued to retain their characteristics. Flow cytometry analysis revealed that CD29, CD44, CD95, CD105 and HLA-I were expressed on the cell surface, but there was no expression of hematopoietic lineage markers, such as CD34, CD38, CD71 and HLA-DR. Chromosomal analysis showed the cells kept a normal karyotype. The cell cycle at the third passage showed the percentage of G0/G1, G2/M and S phase were 88.86%, 5.69% and 5.45%, respectively. The assays in vitro demonstrated the cells exhibited multi-potential differentiation into osteogenic and adipogenic cells. Both BMI-1 and nucleostemin genes, expressed in adult MSCs from bone marrow, were also expressed in umbilical cord MSCs. Here we show that umbilical cords may be a novel alternative source of human MSCs for experimental and clinical applications. [Copyright &y& Elsevier]

Cyclic AMP response element-binding protein (CREB), a transcription factor on which multiple signal transduction pathways converge, has been implicated in long-term memory. We examined whether the sex difference in the performance of contextual fear or passive avoidance conditioning is associated with a change in the activation of CREB in the hippocampus, a neural structure important for long-term memory. The activation of CREB in different subregions within the hippocampus in male and female rats was determined immunohistochemically with an antibody that specifically recognizes the phosphorylated form of CREB (pCREB). With respect to the freezing time in contextual fear conditioning and the step-through latency in passive avoidance conditioning, male rats exhibited better performance than female rats. Phosphorylation of CREB (% pCREB) as revealed by the ratio of the pCREB-immunoreactive (pCREB-ir) cell number to the CREB-immunoreactive cell number was increased in the CA1 region, but not in CA3, CA4, or in the dentate gyrus following training for both types of conditioning in males. In females, such an increase in % pCREB was not found in any hippocampal subregion at any time after conditioning or by increasing the intensity of foot shock. Orchidectomy in males did not alter either the performance of contextual conditioning or conditioning-induced CREB phosphorylation in CA1. The close relationship between behavioral performance and CREB phosphorylation in the CA1 region suggests that hippocampal CREB is involved in the sex difference in some forms of learning and memory. [Copyright &y& Elsevier]

Three compounds, which comprise of benzo[e]indolinium luminophores with two different fluorescence wavelengths, have been synthesized. Those compounds have been prepared by condensation of benzo[e]indolinium and their counterpart aldehydes, and they were confirmed by H-NMR, MS, IR. The absorption and fluorescence spectra of them were tested. The influences of pH value and various solvents on their absorption and fluorescence spectra were summarized. At the same time, self-condensation of benzo[e]indolinium was found in the synthesis of three compounds above. [Copyright &y& Elsevier]

The four kinds of novel naphthalimide dimers were synthesized and their fluorescent lifetimes were investigated. The ground-state/excited state interaction and photo-induced energy/electron transfer in these dimers, which would result in a serial of photochemical properties changes, has been discussed. Using MM2, the energy-minimized molecular modelings of the dimers were studied and confirmed cofacial conformation of chromophores in some dimers, and the pH sensitivity of the dimers has also been detected by fluorescent spectra. [Copyright &y& Elsevier]

The study aims to understand geneome diversification and complexity that developed in Acute myeloid leukemia (AML). Next-generation sequencing (NGS) was used to identify the genetic profiles of 22 genes relevant to hematological malignancy in 204 patients with de novo non-M3 AML. At time of initial diagnosis, at least one mutation was identified in 80.9% of patients (165/204). The most commonly mutated gene was NPM1 (22.1%), followed by ASXL1 (18.1%), TET2 (18.1%), IDH2 (15.7%), CEBPA (14.7%), FLT3-ITD (13.2%) and DNMT3A (11.8%). Mutations landscape analysis indicated several patterns of co-occurring and mutual exclusive gene mutations. Some correlation was observed between gene mutations and clinicohematological features. Multivariate analysis showed that age >60 years, karyotypes, IDH2 and KIT mutations were the independent unfavorable prognostic factors for OS; NPM1-mut/ FLT3-ITD-wt was independently correlated with prolonged OS; whereas the independent poor risk factors for RFS were karyotypes, high WBC and RUNX1 mutation. According to different genotype demonstrated by multivariate analysis, 163 patients with intermediate-risk cytogenetics were classified into three subgroups: patients with NPM1-mut/ FLT3-ITD-wt or biallelic CEBPA mutation as favorable risk, patients with KIT, IDH2, TP53 or NRAS mutations as unfavorable risk, and the remaining was the intermediate risk. We also obtain information of clonal evolution during leukemia progression by observing five patients who underwent repeat NGS at relapse in our cohort. NGS techniques is a useful tool for discovering related gene mutations and clonal evolution in AML genomes, leading to novel targeted therapeutic approaches that could improve patients outcomes. [ABSTRACT FROM AUTHOR]

This document is a letter published in the Annals of Hematology. It reports on a case of an 18-year-old female with Loeys-Dietz syndrome (LDS) and concomitant aplastic anemia (AA). The patient presented with symptoms of generalized pruritus and was diagnosed with AA based on pancytopenia and hypocellular bone marrow. Whole-exome sequencing revealed a SMAD3 mutation in the patient, and subsequent computed tomography angiography (CTA) showed a tortuous right vertebral artery. The letter discusses the findings related to CD8+ T cells and Notch signaling in the patient, suggesting a potential connection between LDS and AA. The patient declined bone marrow transplantation and was treated with eltrombopag and cyclosporin. The authors recommend annual echocardiogram and CTA for monitoring. The study was approved by the Ethics Committee, and written informed consent was obtained from the patient and her guardians. The authors declare no competing interests. [Extracted from the article]

Aim: PAX6 is a transcription factor involved in embryonic development of many organs, including the eyes and the pancreas. Mutations of PAX6 gene is the main cause of a rare disease, congenital aniridia (CA). This case–control study aims to investigate the effects of PAX6 mutations on glucose metabolism and insulin secretion in families with CA. Methods: In all, 21 families with CA were screened by Sanger sequencing. Patients with PAX6 mutations and CA (cases) and age‐matched healthy family members (controls) were enrolled. Oral glucose tolerance test (OGTT) was performed to detect diabetes or impaired glucose tolerance (IGT). Insulin and proinsulin secretion were evaluated. Results: Among 21 CA families, heterozygous PAX6 mutations were detected in five families. Among cases (n = 10) from the five families, two were diagnosed with newly identified diabetes and another two were diagnosed with IGT. Among controls (n = 12), two had IGT. The levels of haemoglobin A1c were 36 ± 4 mmol/mol (5.57 ± 0.46%) and 32 ± 5 mmol/L (5.21 ± 0.54%) in the cases and the controls, respectively (p = 0.049). More importantly, levels of proinsulin in the cases were significantly higher than that of the controls, despite similar levels of total insulin. The areas under the curve of proinsulin in the cases (6425 ± 4390) were significantly higher than that of the controls (3709 ± 1769) (p = 0.032). Conclusion: PAX6 may participate in the production of proinsulin to insulin and heterozygous PAX6 mutations may be associated with glucose metabolism in CA patients. [ABSTRACT FROM AUTHOR]

Background and Purpose: Regulating macrophage-hepatocyte crosstalk through P2X7 receptors has led to new pharmacological strategies to reverse alcoholic hepatosteatosis. We investigated how tetrahydroxystilbene glucoside (2354glu), isolated from Polygonum multiflorum, modulates macrophage-hepatocyte crosstalk during alcoholic hepatosteatosis.Experimental Approach: A model of alcoholic hepatosteatosis was established by giving ethanol intragastrically to C57BL/6 mice. HepG2 cells were incubated in conditioned medium from LPS+ATP-activated THP-1 human macrophages with silenced or overexpressed P2X7 receptors. THP-1 macrophages or mouse peritoneal macrophages were pretreated with 2354glu for 1 hr prior to LPS+ATP stimulation. Western blots, RT-PCR and immunohistochemical analysis were used, along with over-expression and silencing of P2X7 receptors.Key Results: Knockdown or overexpression of P2X7 receptors in THP-1 macrophages affected release of mature IL-1β and, subsequently, modulated lipid metabolism in HepG2 cells via the LKB-AMPK pathway. 2354glu ameliorated alcoholic hepatosteatosis in mice by regulating LKB1-AMPK-SREBP1 pathway and its target genes. Suppression of P2X7 receptor activation by 2354glu inhibited IL-1β release and reduced macrophage and neutrophil infiltration. In macrophages stimulated with LPS+ATP, expression of P2X7 receptors, caspase-1 and NF-κB, release of IL-1β, calcium influx and PI uptake were reduced by 2354glu. SIRT1-LKB1-AMPK-SREBP1 axis-mediated lipid accumulation in HepG2 cells was reduced when they were cultured with conditioned media from LPS+ATP-activated THP-1 macrophages pretreated with 2354glu.Conclusion and Implications: Modulation of P2X7 receptors in macrophages regulated lipid accumulation in hepatocytes during alcoholic hepatosteatosis. 2354glu might be a promising candidate that targets P2X7 receptors in macrophages interacting with hepatocytes during alcoholic hepatosteatosis. [ABSTRACT FROM AUTHOR]

Immunoglobulin heavy chain variable region (IGHV) mutational status has been an important prognostic factor for chronic lymphocytic leukemia (CLL) for decades. Patients with unmutated IGHV (≥98% identity to the germline sequence) have inferior prognosis and tend to carry unfavorable genetic markers compared to those with mutated IGHV (<98% identity to the germline sequence). However, 98% as the cutoff for IGHV mutational status is a mathematical choice and remains controversial. We have previously reported distinct IGHV repertoire features between Chinese and western CLL populations. Here, we retrospectively studied 595 Chinese CLL patients to determine the best cutoff value for IGHV in Chinese CLL population. Using 1% as the interval for IGHV identity, we divided the studied cohort into seven subgroups from 95% to 100%. Briefer time to first treatment (TTFT) and overall survival (OS) were observed in cases with ≥98% compared to those with <98%, while the differences were obscure within subgroups ≥98% (98%‐98.99%, 99%‐99.99%, and 100%) and <98% (<94.99%, 95%‐95.99%, 96%‐96.99%, and 97%‐97.99%). Multivariate analysis confirmed the independent prognostic value of 98% being the cutoff for IGHV identity in terms of both TTFT and OS. All the prognostic factors, including del(17p13), del(11q22.3), TP53 mutation, MYD88 mutation, NOTCH1 mutation, SF3B1 mutation, CD38, ZAP‐70, Binet staging, gender, and β2‐microglobulin, were significantly different in distribution between group <98% and group ≥98%, but not among subgroups 98%‐98.99%, 99%‐99.99%, and 100%. In conclusion, 98% is the optimal cutoff of IGHV identity for the prognosis evaluation of Chinese CLL patients. [ABSTRACT FROM AUTHOR]

Review: 291 refs. [ABSTRACT FROM AUTHOR]

Ultrasound–microwave combined extraction (UMCE), gradient ethanol precipitation, chemical characterization, and antioxidant and hypoglycemic activities of Lycium barbarum leaf polysaccharides (LLP) were systematically studied. The optimal conditions for UMCE of LLP achieved by response surface method (RSM) were as follows: microwave time of 16 min, ultrasonic time of 20 min, particle size of 100 mesh, and ratio of liquid to solid of 55:1. Three novel polysaccharide fractions (LLP30, LLP50, LLP70) with different molecular weights were obtained by gradient ethanol precipitation. Polysaccharide samples exhibited scavenging capacities against ABTS and DPPH radicals and inhibitory activities against α-glucosidase and α-amylase. Among the three fractions, LLP30 possessed relatively high antioxidant and hypoglycemic activities in vitro, which showed a potential for becoming a nutraceutical or a phytopharmaceutical for prevention and treatment of hyperglycemia or diabetes. [ABSTRACT FROM AUTHOR]

Root and tuber crops (RTCs) are the second-most important carbohydrate commodity after cereals. Many species of the RTCs are vegetatively propagated, making their shoot tips the preferred material to be conserved for future uses. Shoot tip cryopreservation provides an important tool to support the long-term conservation of plant genetic resources. Over the past four decades, significant efforts have been undertaken to move shoot tip cryopreservation of RTCs from research projects to full-scale implementation in cryobanks. This comprehensive review focuses on the history of cryopreservation protocols developed in RTCs. The encapsulation and vitrification solution-based cryopreservation techniques followed by ultra-rapid freezing and thawing have been highly successful. Additionally, different strategies for improving the cryotolerance of shoot tips have been introduced to further increase post-cryopreservation recovery. Finally, the research conducted to explain the mechanism underlying cryoprotection and differential cryotolerance including the use of histological studies are highlighted. [ABSTRACT FROM AUTHOR]

Diseases caused by plant pathogens such as viruses, viroids and phytoplasmas cause huge economic losses of agricultural production and limit the safe movement of plant materials across borders. The use of pathogen‐free planting materials provides a strategy for efficient management of these diseases and facilitates the global exchange of genetic resources. Shoot tip cryotherapy is a novel biotechnology method that uses cryogenic procedures to eradicate plant pathogens from the diseased plants. Combining thermotherapy or chemotherapy with shoot tip cryotherapy has further enhanced pathogen eradication efficiency. This review provides updated and comprehensive information on shoot tip cryotherapy and the combination of thermotherapy or chemotherapy with shoot tip cryotherapy for pathogen eradication. Prospects are proposed for future studies. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma progression is thought to be driven by cancer stem cells (CSCs). No clinical trial has, as yet, shown convincing long-term disease free survival results for the majority of patients in HCC. So it is important to discover new anti-cancer agents. In our study, we chose sophocarpine, which is derived from the foxtail-like sophora herb, for its efficacy to inhibit HCC including CSCs and potential mechanism study. Our results show that sophocarpine could not only reduce HCC cell viability, eliminate HCC and reverse hepatoma cells malignant phenotype, but also reduce the ratio of CSCs and inhibit the sphere formation of CSCs in vitro. In vivo, sophocarpine significantly displayed antitumor effects in subcutaneous xenograft HCC models and orthotopic transplantation tumor models. Further studies showed that sophocarpine could exert anti-tumor effects partly via downregulating the activity of the cancer stem cell related pathways and inhibiting EMT induced by TGF-β. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Clinical prognostic value of different NPM1 mutations in acute myeloid leukemia patients" published in a previous issue of the periodical.

Background: Acute myeloid leukemia (AML) patients with various nucleophosmin 1 (NPM1) mutations are controversial in the prognosis. This study aimed to investigate the prognosis of patients according to types of NPM1 mutations (NPM1mut). Methods: Bone marrow samples of 528 patients newly diagnosed with AML, were collected for morphology, immunology, cytogenetics, and molecular biology examinations. Gene mutations were detected by next-generation sequencing (NGS) technology. Results: About 25.2% of cases exhibited NPM1mut. 83.5% of cases were type A, while type B and D were respectively account for 2.3% and 3.0%. Furthermore, 15 cases of rare types were identified, of which 2 cases have not been reported. Clinical characteristics were similar between patients with A-type NPM1 mutations (NPM1A − type mut) and non-A-type NPM1 mutations (NPM1non − A−type mut). Event-free survival (EFS) was significantly different between patients with low NPM1non − A−type mut variant allele frequency (VAF) and low NPM1A − type mut VAF (median EFS = 3.9 vs. 8.5 months, P = 0.020). The median overall survival (OS) of the NPM1non − A−type mutFLT3-ITDmut group, the NPM1A − type mutFLT3-ITDmut group, the NPM1non − A−type mutFLT3-ITDwt group, and the NPM1A − type mutFLT3-ITDwt group were 3.9, 10.7, 17.3 and 18.8 months, while the median EFS of the corresponding groups was 1.4, 5.0, 7.6 and 9.2 months (P < 0.0001 and P = 0.004, respectively). Conclusions: No significant difference was observed in OS and EFS between patients with NPM1A − type mut and NPM1non − A−type mut. However, types of NPM1 mutations and the status of FLT3-ITD mutations may jointly have an impact on the prognosis of AML patients. [ABSTRACT FROM AUTHOR]

The realization of controllable multicomponent self-assembly through reversible supramolecular interactions is a challenging goal, and is an important strategy for the fabrication of switchable nanomaterials. Herein we show that the self-assembly of TiO2 nanoparticles (NP) functionalized with methyl viologen can be controlled both by light irradiation and chemical reduction through cucurbitfSJuril-enhanced radical cation dimerization interactions. Moreover, the controlled assembly and disassembly of this system are accompanied by switchable photocatalytic activity of the TiO2 NPs, which shows potential application as a novel smart and recyclable photocatalyst. [ABSTRACT FROM AUTHOR]

The realization of controllable multicomponent self-assembly through reversible supramolecular interactions is a challenging goal, and is an important strategy for the fabrication of switchable nanomaterials. Herein we show that the self-assembly of TiO2 nanoparticles (NP) functionalized with methyl viologen can be controlled both by light irradiation and chemical reduction through cucurbit[8]uril-enhanced radical cation dimerization interactions. Moreover, the controlled assembly and disassembly of this system are accompanied by switchable photocatalytic activity of the TiO2 NPs, which shows potential application as a novel smart and recyclable photocatalyst. [ABSTRACT FROM AUTHOR]

Background: With the rapid development of next-generation sequencing (NGS) technologies, researchers are making efforts to reveal the genomic landscape of multiple myeloma (MM). However, the clinical significance of many mutations remains poorly defined due to the genetic heterogeneity of MM. To systematically explore the clinical implications of gene mutations and build practical prognostic models, we performed DNA sequencing in newly diagnosed MM patients. Methods: MM cells were purified from bone marrow aspirates using CD138 microbeads and subjected to sequencing with a 387-gene Panel. Nomogram was developed using Cox's proportional hazards model, and candidate variables were screened by stepwise regression. Internal validation was carried out by the bootstrap method. Results: Between July 2016 and December 2020, a total of 147 patients were included in our study. We found patients with a higher mutational load had a significantly shorter progress-free survival (PFS) (19.0 vs. 32.0 months, P = 0.0098) and overall survival (OS) (3-year OS rates were 66.1% and 80.0%, P = 0.0290). Mutations in chromatin regulators (CRs) including KMT2C (14.3%), KMT2D (14.3%), EP300 (11.6%) and ARID gene family (31.3%) were highly frequent in newly diagnosed MM patients. Interestingly, proteins encoded by these genes could form a complex called KMT2C/D COMPASS (KCDCOMs). Patients with mutations of ARID gene family had a significantly shorter PFS (15.5 vs. 34.0 months, P = 0.0003) and OS (3-year OS rates were 64.9% and 81.0%, P = 0.0351) than patients without ARID gene mutations. Incorporating ARID gene mutations into the current staging system could successfully improve their prognostic performance. The PFS and OS nomogram models (including 1q21 copies, ARID gene mutations, extramedullary disease, mutational load and TP53 mutations) showed good predicting performance in both training and validation sets. Conclusion: Our findings emphasized the importance of CRs mutations in newly diagnosed MM patients and indicated the mutations affecting KCDCOMs might promote the development of MM. High mutational load and harboring mutations in the ARID gene family were novel predictors of adverse prognosis in MM. Prognostic models based on gene mutations were commendably prognostic evaluation methods that could provide a reference for clinical practices. [ABSTRACT FROM AUTHOR]

Background: Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of non‐Hodgkin lymphoma. Histone deacetylase inhibitors (HDACis) have been widely applied in multiple tumours, but the expected efficacy was not observed in DLBCL. Therefore, this study is aimed to explore superior HDACis and optimise a relative combinational therapeutic strategy. Methods: The antitumour effects of the drug were evaluated by Cell Counting Kit‐8 (CCK‐8) assay and apoptosis analysis. Single‐cell RNA sequencing (scRNA‐Seq) was used to analyse the intratumoural heterogeneity of DLBCL cells. Whole‐exome sequencing and RNA sequencing were performed to analyse the genetic and transcriptional features. Western blotting, qRT–PCR, protein array, immunohistochemistry, and chromatin immunoprecipitation assays were applied to explore the involved pathways. The antitumour effects of the compounds were assessed using subcutaneous xenograft tumour models. Results: LAQ824 was screened and confirmed to kill DLBCL cells effectively. Using scRNA‐Seq, we characterised the heterogeneity of DLBCL cells under different drug pressures, and c‐Fos was identified as a critical factor in the survival of residual tumour cells. Moreover, we demonstrated that combinatorial treatment with LAQ824 and a c‐Fos inhibitor more potently inhibited tumour cells both in vitro and in vivo. Conclusion: Altogether, we found an HDACi, LAQ824, with high efficacy in DLBCL and provided a promising HDACi‐based combination therapy strategy. [ABSTRACT FROM AUTHOR]

Plant virus eradication is a prerequisite for the use of virus‐free propagules for sustainable crop production. In contrast, virus preservation is required for all types of applied and basic research of viruses. Shoot tip cryopreservation can act as a double‐edged strategy, facilitating either virus eradication or virus preservation in cryoderived plants. Here, we tested the efficacies of shoot tip cryopreservation for virus eradication and preservation in shallot (Allium cepa var. aggregatum). In vitro stock shallot shoots infected with onion yellow dwarf virus (OYDV) and shallot latent virus were thermotreated for 0, 2, and 4 weeks at a constant temperature of 36℃ before shoot tip cryopreservation. Results showed that viruses were preserved in recovered shoots when thermotherapy was not applied. Although thermotherapy lowered the regrowth levels of cryotreated shoot tips, the efficiency of virus eradication increased from 5% to 54%. Immunolocalization of OYDV and histological observation of cryotreated shoot tips showed the high frequency of virus preservation was due to the viral invasion of cells close to the apical meristem and the high proportion of cells surviving. Four weeks of thermotherapy drastically decreased the distribution of OYDV, as well as the percentage of surviving cells within the shoot tips, thereby promoting virus eradication. Virus‐free plants obtained from combining thermotherapy with cryotherapy showed significantly improved vegetative growth and bulb production. The present study reports how thermotherapy can act as a trigger to facilitate either the safe preservation of Allium viruses or the production of virus‐free shallot plants. [ABSTRACT FROM AUTHOR]

Poly(γ-benzyl L-glutamate)/poly(ethylene glycol) (PBLG/PEG) polymer blend membranes were prepared by casting the polymer blend solution in chloroform. Surface morphologies of the polymer blend membranes were investigated by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Thermal and mechanical properties of the polymer blend membranes were researched using differential scanning calorimeter (DSC) and tensile tests. It was revealed that the introduction of PEG could exert outstanding effects on the morphology and the properties of the polymer blend membranes. [ABSTRACT FROM AUTHOR]

A series of poly(vinyl alcohol) (PVA)/polyurethane (PU) blend membranes were prepared by casting the polymer blend solution in dimethyl sulfoxide (DMSO). Structure and morphologies of PVA/PU blend membranes were investigated by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Thermal, mechanical, and chemical properties of PVA/PU blend membrane were studied by differential scanning calorimetry (DSC), tensile tests, and surface contact angle tests. It was found that the introduction of PU could exert marked effects on the morphology and the properties of PVA membrane. [ABSTRACT FROM PUBLISHER]

The human multidrug resistance (MDR1, ABCB1) gene encodes P-glycoprotein (P-gp), which affects the pharmacokinetics of many drugs. Here, we investigated whether common MDR1 single nucleotide polymorphisms (SNPs) (C1236T, C3435T, and G2677T/A) affect predisposition to chronic lymphocytic leukemia (CLL). Genotyping was performed in 150 patients with CLL and 117 controls using polymerase chain reaction (PCR)-based assays. Haplotypes were inferred using the PHASE algorithm. We found comparable allele and genotype frequencies among patients with CLL and controls. Moreover, patient and control groups did not differ regarding MDR1 haplotype distribution ( p == 0.97). Furthermore, no correlation was shown between the MDR1 1236, 3435, or 2677 genotypes and Binet stage, unmutated immunoglobulin heavy-chain variable region (IGHV) status, CD38 expression, ZAP-70 expression, and p53 deletion. In conclusion, our results do not support a major influence of MDR1 variants on the risk of CLL, and these genomic polymorphisms are not associated with clinical prognostic factors in Chinese patients with CLL. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, an ultra performance liquid chromatography coupled with photo-diode array detector and time-of-flight mass spectrometry (UPLC–PDA–TOFMS) based chemical profiling approach to rapidly evaluate chemical consistency between traditional and dispensing granule decoctions of traditional medicine combinatorial formulae was proposed and validated using San–Huang–Xie–Xin–Tang (SHXXT) as a model combinatorial formula. Two different kinds of decoctions, namely traditional decoction: water extract of mixed three constituent herbs of SHXXT, and dispensing granules decoction: mixed water extract of each individual herbs of SHXXT, were prepared. Batches of these two kinds of decoction samples were subjected to UPLC–PDA–TOFMS analysis, the datasets of t R–m/z pairs, ion intensities and sample codes were processed with supervised orthogonal partial least squared discriminant analysis (OPLS–DA) to holistically compare the difference between these two kinds of decoction samples. Once a clear classification trend was found in score plot, further statistics was performed to generate S-plot, in which the variables (t R–m/z pair) contributing most to the difference were clearly depicted as points at the two ends of “S”, and the components that correlate to these ions were regarded as the most changed components during decocting of combinatorial formula. The identities of the changed components can be identified by comparing the mass/UV spectra and retention times with those of reference compounds and/or tentatively assigned by matching empirical molecular formulae with those of the known compounds published in the literatures. Using the proposed approach, global chemical difference was found between traditional and dispensing granule decoctions, and berberine, palmatine, epiberberine, baicalin, wonogoside, 2-O-golloyl-1-O-cinnamoylglucose and emodin were identified as the most changed components during decocting SHXXT. It is suggested that this newly established approach could be used practically for the evaluation of chemical consistency between traditional and dispensing granule decoctions of traditional medicine combinatorial formulae. [Copyright &y& Elsevier]

Abstract: In traditional Chinese medicine, raw and processed herbs are used to treat different diseases. Suitable chemical markers are crucial for the discrimination between raw and processed herbs. In this study, a novel strategy using UHPLC–TOFMS coupled with multivariate statistical analysis to rapidly explore potential chemical markers was proposed and validated. Using Radix Rehmanniae as a model herb, batches of raw and processed samples were determined by UHPLC–TOFMS. The datasets of t R–m/z pair, ion intensity and sample code were subjected to principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) to holistically compare the difference between raw and processed samples. Once a clear cluster was found, extended statistics was performed to generate S-plot, in which the variables (t R–m/z pair) contributing most to the difference were clearly indicated as points at the two ends of “S”, and the components that correlate to these ions should be the processing-induced transformed components. These transformed components could be regarded as the potential chemical markers that can be used to distinguish between raw and processed herbs. The identity of the potential markers can be identified by comparing the mass/UV spectra and retention time with that of reference compounds and/or tentatively assigned by matching empirical molecular formula with that of the known compounds published. Using this proposed strategy, leonuride or its isomer and 5-(α-d-glucopyranosyl-(1-6)-α-d-glucopyranosyloxymethyl)-2-furancarboxaldehyde were rapidly explored as the most characteristic markers of raw and processed Radix Rehmanniae, respectively. This newly proposed strategy can not only be used to explore chemical markers but also to investigate the chemical transforming mechanisms underlying traditional herb processing. [Copyright &y& Elsevier]

Abstract: Polysubstituted 2H-pyran-2-ones and 5,6-dihydro-2H-pyran-2-ones were synthesized via the MCRs initiated by the hydroalkylation of alkynoates with activated methylenes. Under the optimized reaction conditions, the desired products were obtained in 47–88% isolated yields. The experimental results showed that the groups on activated methylenes act important roles in the nucleophilic attack fashion. [Copyright &y& Elsevier]

Abstract: Eleven major isoflavonoids and three major astragalosides in the xylem and bark of cultivated Radix Astragali (RA) from different cultivated regions of China were determined by high performance liquid chromatography. The results showed that the contents of astragalosides in the bark are up to 74-fold higher than in the xylem, and that thin roots contained more astragalosides than thick roots. Although the contents of isoflavonoids varied between samples, no significant difference was observed between the isoflavonoids content of xylem and bark, or between that of thin and thick roots. It was also found that the chemical profile of isoflavonoids in the xylem and bark are related to their cultivated regions. Constituents in either xylem or bark were divided into five groups according to their chemical structures: (1) Group 1 (G1), contained calycosin and related constituents; (2) Group 2 (G2), contained ononin and related constituents; (3) Group 3 (G3), contained (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan and related constituents; (4) Group 4 (G4), contained (3R)-7,2′-dihydroxy-3′,4′-dimethoxyisoflavan and related constituents; and (5) Group 5 (G5), contained astragalosides, compounds AG I, AG II, and AG IV. Based on the integrated contents of constituents in each group, the cultivated region of RA was successfully distinguished by principal components analysis (PCA). Chemical constituents in RA cultivated from different regions of China were compared and it was concluded that the quality of thin RA roots is better than thick RA roots. [Copyright &y& Elsevier]

We report a noise assisted and optimized resonant transition behavior between two metastable Turing pattern states in a piecewise FitzHu–Nagumo model. The response of the bistable Turing system to a weak periodic signal which modulates the attraction domain of the piecewise function is enhanced with the addition of noise. The quantity that measures the resonant transition between the bistable states and the periodicity of the Turing pattern shows a tent-shape dependence on the intensity of noise, which is the fingerprint of stochastic resonance. As the frequency of the signal is increased to be high enough, the coherent transition disappears. [ABSTRACT FROM AUTHOR]

Abstract: A recycling counter-current chromatographic system was first set up with a high-speed counter-current chromatography instrument coupled with a column switching valve. This system was first successfully applied to the preparative separation of epimers, gambogic acid and epigambogic acid from Garcinia hanburyi using n-hexane–methanol–water (5:4:1, v/v/v) as the two-phase solvent system. As a result, 28.2mg gambogic acid and 18.4mg epigambogic acid were separated from 50mg of mixture. Their purities were both above 97% as determined by HPLC. The chemical structures were then identified by their 1H NMR and 13C NMR spectra. [Copyright &y& Elsevier]

Two dimers, based on perylene derivatives linked by urea, were synthesized; both dimers are in linear conformations. Fluorescence lifetimes and fluorescent properties of the dimers were investigated. They show fluorescence quenching in the presence of fluoride ion. The binding constants were calculated by the change of fluorescence, and the values were high (of the order of ∼105M-1). [Copyright &y& Elsevier]

Two novel co-facial folded naphthalimide dimers were synthesized. Strong exciton coupling was observed in the folded dimers as an absorption maximum blue-shift. The fluorescent quenching of the dimers compared to that of monomers and the solvent polarity effect on the quenching efficiency are discussed. The fluorescence lifetimes of the dimers have been also investigated and discussed. [Copyright &y& Elsevier]

Molecular abnormalities are frequent in core-binding factor (CBF) AMLs, but their prognostic relevance is controversial. Sixty-two patients were retrospectively analyzed and 47 harbored at least one gene mutation with a next-generation-sequencing assay. The most common molecular mutation was KIT mutation (30.6%), followed by NRAS (24.2%) and ASXL1 (14.5%) mutations, which was associated with a higher number of bone marrow blasts (p =.049) and older age (p =.027). The survival analysis showed KIT mutation adversely affected the overall survival (OS) (p =.046). NRAS mutation was associated with inferior OS (p =.016) and RFS (p =.039). Eight patients carried co-mutations of KIT and NRAS and had worse OS (p =.012) and RFS (p =.034). The multivariate analysis showed age ≥60 years and additional chromosomal abnormalities were significant adverse factors for OS. Thus, co-mutations of KIT and NRAS were significantly associated with a poor prognosis and should be taken into account when assessing for prognostic stratification in patients with CBF-AML. [ABSTRACT FROM AUTHOR]

A unified description of finite nuclei and equation of state of neutron stars presents both a major challenge and also opportunities for understanding nuclear interactions. Inspired by the Lee–Huang–Yang formula of hard-sphere gases, we develop effective nuclear interactions with an additional high-order density dependent term. While the original Skyrme force SLy4 is widely used in studies of neutron stars, there are not satisfactory global descriptions of finite nuclei. The refitted SLy4' force can improve descriptions of finite nuclei but slightly reduces the radius of neutron star of 1.4M⊙ with M⊙ being the solar mass. We find that the extended SLy4 force with a higher-order density dependence can properly describe properties of both finite nuclei and GW170817 binary neutron stars, including the mass-radius relation and the tidal deformability. This demonstrates the essential role of high-order density dependence at ultrahigh densities. Our work provides a unified and predictive model for neutron stars, as well as new insights for the future development of effective interactions. [ABSTRACT FROM AUTHOR]

The present study described a combining thermotherapy with meristem culture for improved eradication of onion yellow dwarf virus (OYDV) and shallot latent virus (SLV) from co‐infected in vitro‐cultured shallot shoots. In vitro‐cultured shoots infected with OYDV and SLV were thermo‐treated at a constant temperature of 36°C for 0, 2 and 4 weeks, and then meristems (0.5 mm) containing 1–2 leaf primordia were excised and cultured for shoot regrowth. Meristem culture without thermotherapy produced much higher levels of survival (100%) and shoot regrowth (55%) than those (62% survival and 32% shoot regrowth) produced by the procedure combining 4 weeks of thermotherapy with meristem culture. However, much higher virus‐free frequencies (70% for OYSV, 80% for SLV and 50% for both viruses) were obtained in the latter than those (10% for OYSV, 15% for SLV and 10% for both viruses) obtained in the former. Histological and subcellular studies showed that thermotherapy imposed stress or damage to the cells of meristems, thus resulting in reduced meristem survival and shoot regrowth. Studies on virus location revealed considerable alternations of virus distribution patterns in the thermo‐treated meristems. The results of histological and subcellular studies and analysis of virus distribution pattern added valuable experimental data in the combining thermotherapy with meristem culture for virus eradication. These data provided explanations as to why combining thermotherapy with meristem culture improved the eradication of OYDV and SLV from the virus‐infected in vitro shallot shoots. [ABSTRACT FROM AUTHOR]

• Blockade of P2x7R with its selective inhibitor, A438079, reverses thioacetamide-induced liver damage and fibrosis via inhibiting P2x7R-NLRP3 inflammasome activation • Ectopic overexpression of P2x7R lowered the threshold of extracellular matrix (ECM) deposition in HSCs • Macrophages stimulated by LPS/ATP aggravated ECM deposition in HSCs through activating P2x7R • IL-1β secreted by LPS/ATP activated macrophages amplifies the fibrosis signal from macrophages HSCs (hepatic stellate cells) contribute to the excessive extracellular matrix (ECM) deposition, inflammatory pathways and crucial cell-cell interactions in hepatic disease leading to fibrosis. P2x7R is considered a potential orchestrater in liver fibrosis. For this reason, this work explored the role of P2x7R in liver fibrosis and the mechanism by which P2x7R in macrophages promotes fibrogenesis. In a model of liver fibrosis induced by administration of thioacetamide (TAA), inhibition of P2x7R with its selective inhibitor A438079 reversed TAA-induced liver damage and fibrosis. The mechanism was linked to inhibition of P2x7R-NLRP3 inflammasome activation and thereby infiltration of macrophages and neutrophils into the liver. This result indicated that the P2x7R-TLR4-NLRP3 axis is involved in the process of TGF-β-mediated ECM deposition in HSCs. Ectopic overexpression of P2x7R lowered the threshold of extracellular matrix (ECM) deposition and maintained HSCs in an activated state. The culture medium of THP-1 macrophages stimulated by LPS/ATP aggravated ECM deposition in HSCs by activating P2x7R. Additionally, IL-1β secreted by LPS / ATP activated macrophages amplified fibrosis. These data indicate that P2x7R plays a key regulative role in the activation and maintenance of HSCs promoted by macrophages. Thus, pharmacological inhibition of P2x7R could be a potential therapeutic mechanism to treat human liver fibrosis. [ABSTRACT FROM AUTHOR]