Background: Monocyte chemoattractant protein 1 (MCP-1) is a member of the C-C chemokine family and exerts strong chemoattractant activity in monocytes, macrophages, and lymphocytes. Rat pancreatic ...fibrosis induced by dibutyltin dichloride (DBTC) is considered to be an appropriate chronic pancreatitis model histologically and enzymatically, as has demonstrated in a previous study. Aim: We examined the effect of human dominant negative inhibitor of MCP-1 (mutant MCP-1) on progression of chronic pancreatitis induced by DBTC in a rat model. Methods: We used the experimental model of chronic pancreatitis induced by DBTC in rats. Mutant MCP-1 or empty plasmid at a dose of 50 µg/body weight was administrated into rat thigh muscles on days 4, 11, and 18 after administration of DBTC. On days 14 and 28, we evaluated the effect of mutant MCP-1 morphologically and biochemically. Results: The mutant MCP-1 treated group inhibited early pancreatic inflammation and later pancreatic fibrosis histologically, and showed a decrease in serum MCP-1 concentration, intrapancreatic hydroxyproline, α-smooth muscle actin, and an increase in intrapancreatic amylase and protein content compared with the empty plasmid treated group. The mutant MCP-1 group also inhibited intrapancreatic mRNA expression of cytokines and chemokines. Conclusions: : Our findings suggest that monocyte/macrophage recruitment and the systemic MCP-1 signal pathway contribute to progression of chronic pancreatitis, and that blockade of MCP-1 may suppress the development of pancreatic fibrosis.
Plants that have evolved to survive on metal‐rich soils—metallophytes—have key values that must drive research of their unique properties and ultimately their conservation. The ability of ...metallophytes to tolerate extreme metal concentrations commends them for revegetation of mines and metal‐contaminated sites. Metallophytes can also be exploited in environmental technologies, for example, phytostabilization, phytoremediation, and phytomining. Actions towards conserving metallophyte species are imperative, as metallophytes are increasingly under threat of extinction from mining activity. Although many hundreds of papers describe both the biology and applications of metallophytes, few have investigated the urgent need to conserve these unique species. This paper identifies the current state of metallophyte research, and advocates future research needs for the conservation of metallophyte biodiversity and the sustainable uses of metallophyte species in restoration, rehabilitation, contaminated site remediation, and other nascent phytotechnologies. Six fundamental questions are addressed: (1) Is enough known about the global status of metallophytes to ensure their conservation? (2) Are metallophytes threatened by the activities of the minerals industry, and can their potential for the restoration or rehabilitation of mined and disturbed land be realized? (3) What problems exist in gaining prior informed consent to access metallophyte genetic resources and how can the benefits arising from their uses be equitably shared? (4) What potential do metallophytes offer as a resource base for phytotechnologies? (5) Can genetic modification be used to “design” metallophytes to use in the remediation of contaminated land? (6) Does the prospect of using metallophytes in site remediation and restoration raise ethical issues?
Since the majority of melanomas eventually become resistant and progress, combining selective BRAF inhibitors (BRAFi) with immunotherapies has been proposed to achieve more durable treatment ...responses. Here, we explored the impact of selective BRAFi on the hosts' immune system.
Clinical data, whole blood counts (WBC) and serum lactate dehydrogenase (LDH) of 277 vemurafenib- and 65 dabrafenib-treated melanoma patients were evaluated. The frequency and phenotype of lymphocyte subpopulations were determined by flow cytometry while T cell cytokine secretion was measured by multiplex assays.
Progression-free survival (PFS) as well as overall survival (OS) were similar in patients treated with either BRAFi. High pretreatment LDH was associated with shorter PFS and OS in both groups. During therapy, peripheral lymphocytes decreased by 24.3% (median, P < 0.0001) in vemurafenib-treated patients but remained unchanged in dabrafenib-treated patients (+1.2%, P = 0.717). Differentiation of peripheral lymphocytes of vemurafenib-treated patients showed a significant decrease in CD4+ T cells (P < 0.05). Within CD4+ T cells obtained during treatment, an increase in CCR7+CD45RA+ (naïve) and a decrease in CCR7+CD45RA- (central memory) populations were found (P < 0.01 for both). Furthermore, secretion of interferon-γ and interleukin-9 by CD4+ T cells was significantly lower in samples obtained during vemurafenib treatment compared with baseline samples.
While both compounds have comparable clinical efficacy, vemurafenib but not dabrafenib decreases patients peripheral lymphocyte counts and alters CD4+ T cell phenotype and function. Thus, selective BRAFi can significantly affect patients' peripheral lymphocyte populations. Fully understanding these effects could be critical for successfully implementing combinatorial therapies of BRAFi with immunomodulatory agents.
The charge density wave (CDW) is usually associated with Fermi surfaces nesting. We here report a new CDW mechanism discovered in a 2H-structured transition metal dichalcogenide, where the two ...essential ingredients of the CDW are realized in very anomalous ways due to the strong-coupling nature of the electronic structure. Namely, the CDW gap is only partially open, and charge density wave vector match is fulfilled through participation of states of the large Fermi patch, while the straight Fermi surface sections have secondary or negligible contributions.
Purpose: For better understanding of radiotherapy resistance and its potential mechanism. Methods: We established radioresistance cell lines of non-small cell lung cancer (NSCLC) followed by ...microarray analysis. 529 differentially expressed genes (DEGs) were then screened between radiation resistant cell lines compared with the sensitive cell lines. The biological functions and enrichment pathways of the above DEGs were identified using Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses. Gene Set Enrichment Analysis (GSEA) revealed that the radiation resistance group had the most gene sets enriched in altered immune response, such as TNF signaling pathway, when compared to the radiation sensitive group. Protein-protein interaction (PPI) network was carried out through the STRING database, and then five hub genes (CXCL10, IFIH1, DDX58, CXCL11, RSAD2) were screened by Cytoscape software. RT-PCR confirmed the expression of the above hub genes. ChIP-X Enrichment Analysis showed that STAT1 might be the transcription factor of the above hub genes. Considering that PD-L1 could be activated by STAT1 in a variety of tumors and ultimately lead to immune exhaustion, RT-PCR and Western blot verified the expression level of PD-L1. Results: Five hub genes (CXCL10, IFIH1, DDX58, CXCL11, RSAD2) were screened and verified to be highly expressed in radioresistance group, STAT1 might be the transcription factor of the above hub genes. Our study found that the expression level of PD-L1 was increased after radiotherapy resistance. Conclusion: Although immune system activation occurs followed by radiation resistance, we hypothesized that the upregulation of PD-L1 expression caused by STAT1 activation might be one of the mechanisms of radiotherapy resistance. Keywords: NSCLC, radioresistance, DEGs, hub gene, STAT1
The exhaust gas, CO and H2, occupy about a half amount of combustion products, and they make the oxidative reaction with oxygen in the ambient air entraining into the plume during the combustion of ...solid propellants, producing shock wave, visible flash and increased infrared radiation. In order to inhibit the afterburning plume of solid rocket motors, one of the best ways is to utilize potassium salts as suppression in the propellant formulation. This review discussed and summarized the influence of a great number of potassium salts including inorganic (K2SO4, KHCO3, KCl, KNO3, KBF4, and K3Co(NO2)6 etc.) and organic (K2C2O4, Potassium biphthalate, KD, energetic K(NNMPA) and ADNPK) compounds on the decomposition kinetics, flame structures and temperature, burning rate, combustion wave structures, quenched surface of solid propellants, especially the plateau burning effect. The equipment of plume tests involves in the pressure differential scanning calorimetry, infrared (IR) radiation signature, afterburning flame length and nitrogen-filled pressure-regulating burner etc. The mechanism by which chemical inhibition occurs when certain powders are added to fuel-air flames was shown and discussed. Moreover, the exhaust properties and electron density of solid propellants were modeled and calculated. Finally, future research trends are suggested from different perspectives involving the KOH testing inside the solid rocket motors, plume signature testing and novel insoluble K compounds.
To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China.
...Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline.
A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the
(95%
) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/
Two experiments were conducted to develop a computer-controlled digestion system to simulate the digestion process of duck for predicting the concentration of ME and the metabolizability of gross ...energy (GE) in corn. In a calibration experiment, 30 corn-based calibration samples with a previously published ME concentration in 2008 were used to develop the prediction models for in vivo energetic values. The linear relationships were established between in vivo ME concentration and in vitro digestible energy (IVDE) concentration, and between in vivo metabolizability of GE (ME/GE) and in vitro digestibility of GE (IVDE/GE), respectively. In a validation experiment, 6 sources of corn with previously published ME concentration in 2008 randomly selected from the primary corn-growing regions of China were used to validate the prediction models established in the calibration experiment. The results showed that in calibration samples, the IVDE concentration was positively correlated with the AME (r = 0.9419), AMEn (r = 0.9480), TME (r = 0.9403), and TMEn concentration (r = 0.9473). Similarly, the IVDE/GE was positively correlated with the AME/GE (r = 0.95987), AMEn/GE (r = 0.9641), TME/GE (r = 0.9588), and TMEn/GE (r = 0.9637). The coefficient of determination greater than 0.88 and 0.91, and residual SD less than 45 kcal/kg of DM and 1.01% were observed in the prediction models for ME concentrations and ME/GE, respectively. Twenty-nine out of 30 calibration samples showed differences less than 100 kcal/kg of DM and 2.4% between determined and predicted values for 4 ME (AME, AMEn, TME, and TMEn) and for 4 ME/GE (AME/GE, AMEn/GE, TME/GE, and TMEn/GE), respectively. Using prediction models developed from 30 calibration samples, 6 validation samples further showed differences less than 100 kcal/kg of DM and 2% between determined and predicted values for ME and ME/GE, respectively. Therefore, the computer-controlled simulated digestion system can be used to predict the ME and ME/GE of corn for ducks with acceptable accuracy.
A series of pseudo-quinary Ti20Zr20Hf20Be20(Cu20-xNix) (x=2.5, 5, 7.5, 10, 12.5, 15, 17.5 and 20at.%) high entropy bulk metallic glasses (HE-BMGs) with large glass forming ability (GFA) were ...successfully prepared by copper mold tilt-casing. The critical diameters (Dc) of these HE-BMGs are all above 12mm. In particular, the developed Ti20Zr20Hf20Be20(Cu7.5Ni12.5) and Ti20Zr20Hf20Be20Ni20 high entropy alloys (HEAs) can be produced in the amorphous state with diameters up to 30mm and 15mm, respectively, which are the largest HE-BMG and quinary HE-BMG hitherto. The two HE-BMGs also exhibit high yield strength, together with the plastic strain values of (3.0±1.1) % and (4.0±0.9) %, respectively. With increasing Ni additions in the pseudo-quinary HEAs, the crystallization growth resistance and thermal stability have been improved, which is apparently due to the sluggish diffusion of the atoms in the HEAs.
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•These high entropy bulk metallic glasses (HE-BMGs) have large glass-forming ability.•These HE-BMGs have a critical diameter up to 30mm.•This is the largest size in the HE-BMGs reported so far.•All the developed HE-BMGs exhibit good mechanical properties.•The developed HE-BMGs possess high thermal stability.
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