Profiles of cytokines in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Objective: This study aimed to identify plasma biomarkers that are significantly altered in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and are closely associated with AAV disease activity, as well as to explore their role in the pathogenesis of AAV. Methods: Cytokines were measured using Human Immune Response Panel 80-Plex in plasma from 59 patients with AAV and 20 healthy controls (HCs). The differentially expressed cytokines between the two groups and the possible signaling pathway involved in the pathogenesis of AAV were analyzed by bioinformatics. Relationship analysis was performed between these cytokines and clinical parameters to identify the biomarkers that can effectively indicate disease activity. Results: We identified 65 differentially expressed cytokines between the two groups. Among them, 43 cytokines significantly affected the risk of AAV. Bioinformatic analysis showed that the 43 cytokines were primarily enriched in signaling pathways such as cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, chemokine signaling pathway, and IL-17 signaling pathway. The levels of 25 cytokines were significantly positively correlated with Birmingham Vasculitis Activity Score (BVAS), and the levels of 2 cytokines were significantly negatively correlated with BVAS. Receiver operating characteristic analysis showed that 9 cytokines can distinguish between disease relapse and remission (PTX3: area under curve (AUC)=0.932, IL34: AUC=0.856, IL2RA: AUC=0.833, CCL23: AUC=0.826, VEGFA: AUC=0.811, TNFSF13: AUC=0.795, Granzyme A: AUC=0.788, CSF3: AUC=0.773 and IL1A: AUC=0.765). The elevated levels of these 9 cytokines suggested a risk of disease relapse. The AUC of CCL11 in disease relapse and remission was 0.811 (p=0.0116). Unlike the other 9 cytokines, a negatively association existed between CCL11 level and the risk of disease relapse. Conclusion: A group of cytokines that may be involved in AAV pathogenesis was identified. Increased PTX3, IL34, IL2RA, CCL23, and VEGFA levels correlate with active disease in AAV and may be used as biomarkers to identify the disease relapse of AAV.

Secondary formation of oxygenated and nitrated polycyclic aromatic compounds under stagnant weather conditions: Drivers and seasonal variation.

Severe air pollution tends to occur under stagnant weather conditions. This study focused on the occurrence and formation of PM2.5-bound polycyclic aromatic compounds (PACs) under stagnant weather conditions, in consideration of their adverse human health effect and ecological toxicity. The concentrations of PACs were higher under stagnant weather conditions than in other situations with averaged values of 46.0 ng/m3 versus 12.3-39.9 ng/m3 for total PACs. Secondary formation contributed to over half of the oxygenated and nitrated polycyclic aromatic compounds (OPAHs and NPAHs). Further analyses revealed different formation mechanisms for secondary OPAHs and NPAHs. Secondary production of OPAHs was sensitive to the variations of both temperature (T) and O3 concentration at T < 22 °C but sustained at a high level despite the fluctuation of temperature and O3 concentration at T > 22 °C. Elevated NO2 concentrations favored the formation of inorganic nitrogen-containing products over NPAHs under lower temperature and higher humidity. Stagnant weather events, accompanied by raised PAC levels occurred in all seasons, but their effects on secondary processes differed among seasons. The elevated temperature, lowered humidity, and increased NO2 level facilitated the secondary formation of OPAHs and/or NPAHs during the stagnant weather events in spring and summer. While under the temperature and humidity conditions in autumn and winter, increased NO2 levels during stagnant weather events promoted the production of secondary inorganic nitrogen-containing compounds over organic products. This study raised concern about the toxic organic pollutants in the atmosphere under stagnant weather conditions and revealed different formation mechanisms between secondary oxygenated and nitrated pollutants as well as among different seasons.

S100P as a potential biomarker for immunosuppressive microenvironment in pancreatic cancer: a bioinformatics analysis and in vitro study.

BACKGROUND: Immunosuppression is a significant factor contributing to the poor prognosis of cancer. S100P, a member of the S100 protein family, has been implicated in various cancers. However, its role in the tumor microenvironment (TME) of pancreatic cancer remains unclear. This study aimed to investigate the potential impact of S100P on TME characteristics in patients with pancreatic cancer. METHODS: Multiple data (including microarray, RNA-Seq, and scRNA-Seq) were obtained from public databases. The expression pattern of S100P was comprehensively evaluated in RNA-Seq data and validated in four different microarray datasets. Prognostic value was assessed through Kaplan-Meier plotter and Cox regression analyses. Immune infiltration levels were determined using the ESTIMATE and ssGSEA algorithms and validated at the single-cell level. Spearman correlation test was used to examine the correlation between S100P expression and immune checkpoint genes, and tumor mutation burden (TMB). DNA methylation analysis was performed to investigate the change in mRNA expression. Reverse transcription PCR (RT-PCR) and immunohistochemical (IHC) were utilized to validate the expression using five cell lines and 60 pancreatic cancer tissues. RESULTS: This study found that S100P was differentially expressed in pancreatic cancer and was associated with poor prognosis (P < 0.05). Notably, S100P exhibited a significant negative-correlation with immune cell infiltration, particularly CD8 + T cells. Furthermore, a close association between S100P and immunotherapy was observed, as it strongly correlated with TMB and the expression levels of TIGIT, HAVCR2, CTLA4, and BTLA (P < 0.05). Intriguingly, higher S100P expression demonstrated a negative correlation with methylation levels (cg14323984, cg27027375, cg14900031, cg14140379, cg25083732, cg07210669, cg26233331, and cg22266967), which were associated with CD8 + T cells. In vitro RT-PCR validated upregulated S100P expression across all five pancreatic cancer cell lines, and IHC confirmed high S100P levels in pancreatic cancer tissues (P < 0.05). CONCLUSION: These findings suggest that S100P could serve as a promising biomarker for immunosuppressive microenvironment, which may provide a novel therapeutic way for pancreatic cancer.

Experimental Study on the Application of Recycled Concrete Waste Powder in Alkali-Activated Foamed Concrete.

The alkali-activated cementitious material was prepared by partially replacing slag with recycled concrete powder (RCP). The influence of RCP substitution rates (10%, 20%, 30%, 40%, and 50% mass fraction) on the performance of alkali-activated slag-RCP-based (AASR) foamed concrete was studied. The fluidity, water absorption, softening coefficient, compressive strength, flexural strength, drying shrinkage, thermal conductivity, and frost resistance of AASR foamed concrete were studied. The results show that the fluidity and softening coefficient of AASR foamed concrete decreases with the increase in RCP content, and the fluidity range is 230-270 mm. Due to the porous structure of the RCP, the water absorption of AASR increases. With the increase in the curing age, the strength of AASR foamed concrete increases. The addition of RCP reduced the mechanical properties of AASR foamed concrete. Compared with the control group, the compressive strength of AASR50 decreased by 66.7% at 28 days, and the flexural strength decreased by 61.5%. However, the 28 d compressive strength of AASR foamed concrete under all RCP replacement rates still meets the standard value (0.6 MPa). The addition of RCP effectively reduces the thermal conductivity of the AASR foamed concrete, and when the RCP content is 50%, the thermal conductivity is lowest, 0.119 W/(m·K); the drying shrinkage of the AASR foamed concrete can be improved by adding RCP, and the drying shrinkage value is lowest when the RCP is 30%, which is 14.7% lower than that of the control group. The frost resistance of AASR foamed concrete decreases with the increase in the RCP content. When the recycled micropowder content is 20-50% and after 25 freeze-thaw cycles, AASR foamed concrete has reached freeze-thaw damage.

Full-Dimensional Analysis of Electrolyte Decomposition on Cathode-Electrolyte Interface: Establishing Characterization Paradigm on LiNi0.6Co0.2Mn0.2O2 Cathode with Potential Dependence.

Cathode electrolyte interphase (CEI) layers derived from electrolyte oxidative decomposition can passivate the cathode surface and prevent its direct contact with electrolyte. The inorganics-dominated inner solid electrolyte layer (SEL) and organics-rich outer quasi-solid-electrolyte layer (qSEL) constitute the CEI layer, and both merge at the junction without a clear boundary, which assures the CEI layer with both ionic-conducting and electron-blocking properties. However, the typical "wash-then-test" pattern of characterizations aiming at the microstructure of CEI layers would dissolve the qSEL and even destroy the SEL, leading to an overanalysis of electrolyte decomposition pathway and misassignment of CEI architecture (e.g., component and morphology). In this study, we established a full-dimensional characterization paradigm (combining Fourier transform infrared, solution NMR, X-ray photoelectron spectroscopy, and mass spectrometry technologies) and reconstructed the original CEI layer model. Besides, the feasibility of this characterization paradigm has been verified in a wide operating voltage range on a typical LiNixMnyCozO2 cathode.

Effectiveness of Chinese medicine formula Huashibaidu granule on mild COVID-19 patients: A prospective, non-randomized, controlled trial.

Background: The effectiveness and safety of Huashibaidu granule (HSBD) in treating mild Corona Virus Disease 2019 (COVID-19) patients infected with SARS-CoV-2 remain to be identified. We aimed to evaluate the effectiveness of HSBD in mild COVID-19 patients. Methods: A prospective, non-randomized, controlled study in mild COVID-19 patients was conducted in Shanghai, from April 8 to May 6, 2022. The enrolled patients were diagnosed as mild COVID-19. Finally, 360 patients received HSBD, and 368 patients received TCM placebo (administered orally 20 g twice daily for 7 days). The primary endpoints were the negative conversion rate of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the negative conversion time. Secondary endpoints included the hospitalized days and the improvement in the clinical condition. Results: The negative conversion rate of SARS-CoV-2 at 7 days posttreatment in the HSBD group was higher than that in the control group (95.28% vs. 82.61%, P < 0.001). The median negative conversion time in the HSBD group was markedly decreased by 2 days compared with the control group (3 [3-6] vs. 5 [4-7], P < 0.001). In addition, the median hospitalized day was shortened in the HSBD group by 1 day compared with the control group (6 [4-7] vs. 7 [5-9], P < 0.001). The clinical improvement rate (275/360 [76.39%]) in the HSBD group within 7 days was significantly higher than that (203/368 [55.16%]) in the control group (P < 0.001). The improvement of symptom scores in the HSBD group was higher than that in the control group (2 [1-4] vs. 1 [1-2], P < 0.001). No severe adverse events occurred. Conclusions: Our study suggested that HSBD effectively increased the negative conversion rate of SARS-CoV-2 and shortened the negative conversion time and hospitalized days in mild COVID-19 patients. Clinical trial registration: Chinese Clinical Trial Registry, ChiCTR2200058668.

Distinct seasonal variability of source-dependent health risks from PM2.5-bound PAHs and related derivatives in a megacity, southwest China: Implications for the significance of secondary formation.

In contrast to polycyclic aromatic hydrocarbons (PAHs) which have been regularly monitored, the source-dependent health risk of their derivatives in ambient environment has not been well understood, especially regarding seasonal variability. In this study, oxygenated and nitrated PAHs (OPAHs and NPAHs) in PM2.5 samples from different seasons in urban Chongqing were analyzed and compared with PAHs from a human health perspective. Benzo[a]pyrene equivalent concentrations (BaPeq) were annually averaged at 6.13 ± 8.97 ng/m3 (n = 118) in the present study, with highest levels in winter followed by spring, autumn, and summer. The BaPeq values of OPAHs were higher than PAHs in spring and summer with seasonal averaged value up to 3.7 times of that for PAHs, manifesting significant underestimation of the health impact if only PAHs were considered. Incremental lifetime cancer risk (ILCR) model results suggested that the potential cancer risks were accumulated mostly from inhalation exposure during infancy and adulthood. Furthermore, in comparison with PAHs, OPAHs, mainly 6H-Benzo[c,d]pyren-6-one, had significant contribution to cancer risks (annually averaged at 58.3 %). Source-dependent cancer risks based on positive matrix factorization model denoted secondary formed PAH derivatives as a critical contributor to cancer risk, particularly in spring and summer (attributed to about 61 % of ILCR). The enhanced secondary formation of PAH derivatives during spring and summer was partially justified by diagnostic ratios and further analysis revealed that higher temperature, higher O3 level, and lower relative humidity besides stronger solar intensity during these two seasons as the most likely causes of this seasonal variation. Results in this study emphasizes that more knowledge on the formation and toxicity of OPAHs is imperative, especially in the context of complex PM2.5-ozone pollution in China.

Visualizing Cathepsin K-Cre Expression at the Single-Cell Level with GFP Reporters.

The Cre/lox system is a fundamental tool for functional genomic studies, and a number of Cre lines have been generated to target genes of interest spatially and temporally in defined cells or tissues; this approach has greatly expanded our knowledge of gene functions. However, the limitations of this system have recently been recognized, and we must address the challenge of so-called nonspecific/off-target effects when a Cre line is utilized to investigate a gene of interest. For example, cathepsin K (Ctsk) has been used as a specific osteoclast marker, and Cre driven by its promoter is widely utilized for osteoclast investigations. However, Ctsk-Cre expression has recently been identified in other cell types, such as osteocytes, periosteal stem cells, and tenocytes. To better understand Ctsk-Cre expression and ensure appropriate use of this Cre line, we performed a comprehensive analysis of Ctsk-Cre expression at the single-cell level in major organs and tissues using two green fluorescent protein (GFP) reporters (ROSA nT-nG and ROSA tdT) and a tissue clearing technique in young and aging mice. The expression profile was further verified by immunofluorescence staining and droplet digital RT-PCR. The results demonstrate that Ctsk-Cre is expressed not only in osteoclasts but also at various levels in osteoblast lineage cells and other major organs/tissues, particularly in the brain, kidney, pancreas, and blood vessels. Furthermore, Ctsk-Cre expression increases markedly in the bone marrow, skeletal muscle, and intervertebral discs in aging mice. These data will be valuable for accurately interpreting data obtained from in vivo studies using Ctsk-Cre mice to avoid potentially misleading conclusions. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

KIFC3 promotes proliferation, migration and invasion of esophageal squamous cell carcinoma cells by activating EMT and ß-catenin signaling.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. A total of 45 kinesin superfamily proteins (KIFs) have been identified in humans, among which several family members have demonstrated varied functions in tumor pathobiology via different mechanisms, including regulation of cell cycle progression and metastasis. KIFC3 has microtubule motor activity and is involved in cancer cell invasion and migration, as well as survival. However, the role of KIFC3 in ESCC is still unknown. AIM: To evaluate the role of KIFC3 in ESCC and the underlying mechanisms. METHODS: Expression of KIFC3 was evaluated in ESCC tissues and adjacent normal esophageal tissues. The prognostic value of KIFC3 was analyzed using Kaplan-Meier Plotter. Colony formation, EdU assays, cell cycle analysis, Transwell assay, immunofluorescence, and western blotting were performed in ESCC cell lines after transfection with pLVX-Puro-KIFC3-shRNA- and pLVX-Puro-KIFC3-expressing lentiviruses. A xenograft tumor model in nude mice was used to evaluate the role of KIFC3 in tumorigenesis. Inhibitor of ß-catenin, XAV-939, was used to clarify the mechanism of KIFC3 in ESCC. To analyze the differences between groups, t test and nonparametric tests were used. P < 0.05 was considered statistically significant. RESULTS: Immunohistochemical staining indicated that KIFC3 was upregulated in ESCC tissues compared with adjacent normal tissues. Kaplan-Meier Plotter revealed that overexpressed KIFC3 was associated with poor prognosis in ESCC patients. Colony formation and EdU assay showed that KIFC3 overexpression promoted cell proliferation, while KIFC3 knockdown inhibited cell proliferation in ESCC cell lines. In addition, cell cycle analysis showed that KIFC3 overexpression promoted cell cycle progression. KIFC3 knockdown suppressed ESCC tumorigenesis in vivo. Transwell assay and western blotting revealed that KIFC3 overexpression promoted cell migration and invasion, as well as epithelial-mesenchymal transition (EMT), while KIFC3 knockdown showed the opposite results. Mechanistically, KIFC3 overexpression promoted ß-catenin signaling in KYSE450 cells; however, the role of KIFC3 was abolished by XAV-939, the inhibitor of ß-catenin signaling. CONCLUSION: KIFC3 was overexpressed in ESCC and was associated with poor prognosis. Furthermore, KIFC3 promoted proliferation, migration and invasion of ESCC via ß-catenin signaling and EMT.

Salidroside attenuates cardiac dysfunction in a rat model of diabetes.

AIM: This study aimed to investigate the therapeutic effects of salidroside on diabetes-induced cardiovascular disease. METHODS: Sprague-Dawley rats treated with 65 mg/kg of streptozotocin (STZ) on a daily basis were used to establish the diabetic rat model (blood glucose levels >13.9 mmol/L). Cardiac functions of diabetic rats were evaluated by their haemodynamic alterations. Western blot assay was performed to evaluate the protein levels of multiple signalling pathway factors. Quantitative real-time PCR assay was performed to investigate the inflammation and oxidative stress of diabetic rats. RESULTS: Salidroside treatment improved the cardiac functions of diabetic rats. In addition, salidroside therapy attenuated the cardiac oxidative stress induced by diabetes. Salidroside inhibited the diabetes-induced inflammation in diabetic rat hearts. The apoptosis of cardiomyocytes was also alleviated by the treatment of salidroside. Salidroside also upregulated the phosphorylation levels of AMPK, ACC, TSC2 and RAPTOR. CONCLUSION: Salidroside exerts protective effects against diabetes-induced cardiac dysfunction by modulating the mTOR and AMPK signalling pathways.

Green Process for 5-(Chloromethyl)furfural Production from Biomass in Three-Constituent Deep Eutectic Solvent.

5-(Chloromethyl)furfural (CMF), a versatile bio-platform molecule, was first synthesized in a three-constituent deep eutectic solvent (3c-DES) including choline chloride, AlCl3 ⋅ 6H2 O, and oxalic acid. In particular, 3c-DES was conducive for the production of CMF from glucose and provided a CMF yield of 70 % at 120 °C within 30 min. In addition, CMF yields reached up to 86, 80, 30, 29, and 35 % from fructose, sucrose, cellulose, bamboo, and bamboo pulp, respectively. This study opens new avenues for the preparation of CMF.

Circular RNA MTO1 inhibits gastric cancer progression by elevating PAWR via sponging miR-199a-3p.

The effect of circular RNA MTO1 (circMTO1) signaling on the expression of miR-199a-3p in gastric carcinoma cells, and its effect on proliferation and apoptosis of gastric cancer cells were investigated in this study. RT-qPCR was performed to detect the expression levels of circMTO1 and miR-199a-3p in the cell lines and tissues of gastric cancer. The effect of circMTO1 and miR-199a-3p on the growth and apoptosis of tumor cells was detected by BrdU incorporation and Annexin V/PI staining. Target gene prediction and screening, and luciferase reporter assays were performed to validate downstream interested genes of circMTO1 and miR-199a-3p. The expression levels of miR-199a-3p target gene PAWR (named as PRKC apoptosis WT1 Regulator Protein) was measured by RT-qPCR and Western blotting. Tumor changes in mice were detected by transfecting circMTO1. The expression of circMTO1 was significantly downregulated in the cell lines and tissues of gastric cancer, and low expression levels of circMTO1 were closely associated with poor prognosis. Overexpression of circMTO1 inhibited tumor growth, enhanced apoptosis rate and decreased cell invasion and migration. There was a significant negative relationship between the expression levels of circMTO1 and miR-199a-3p in gastric cancer tissues. Inhibiting miR-199a-3p expression or overexpression of PAWR could decrease the promotive effects of knockdown of circMTO1 on the progression of gastric cancer, and a positive relationship was established between the expression of circMTO1 and PAWR. circMTO1 can regulate the growth of gastric cancer cells by regulating miR-199a-3p/PAWR axis, thus inhibiting the development and progression of gastric cancer. Abbreviation GC: Gastric cancer; circ RNA: Circular RNA; MTO1: mitochondrial translation optimized 1 homolog.

The Construction and Immunoadjuvant Activities of the Oral Interleukin-17B Expressed by Lactobacillus plantarum NC8 Strain in the Infectious Bronchitis Virus Vaccination of Chickens.

Interleukin-17B (IL-17B) is a protective cytokine of the IL-17 family and plays an essential role in the regulation of mucosal inflammation. However, little is known about the role of IL-17B in the control of viral infections. In this study, a recombinant Lactobacillus plantarum, designated as NC8-ChIL17B, was constructed to express the chicken IL-17B (ChIL-17B) gene. The recombinant ChIL17B (rChIL17B) protein was about 14 kDa and was anchored to the surface of NC8 cells. In vitro, it was found that the rChIL17B protein inhibited the proliferation of the infectious bronchitis virus (IBV) through activation of nuclear factor kappa B (NF-κB) and the JAK (Janus kinase)-STAT (signal transducers and activators of transcription) signaling. Moreover, to evaluate the immunoadjuvant activities of NC8-ChIL17B, 40 three-day-old specific pathogen-free (SPF) chickens were divided into four groups. Three groups were orally vaccinated with fresh NC8, NC8-ChIL17B, and phosphate buffered saline (PBS), along with the infectious bronchitis virus vaccine, and the other group was the PBS-negative control. The results of the IBV-specific antibody titer and the concentration of the cytokines IL-2, IL-4, IL-6, and interferon gamma (IFN-γ) in sera, as well as the concentration of secretory immunoglobulin A (sIgA) in the tracheal and small intestinal mucosa, the number of cluster of differentiation 4 positive (CD4+) and cluster of differentiation 8 positive (CD8+) T cells in the blood, and the expression of immune-related genes all indicated that NC8-ChIL17B efficiently enhanced the humoral and cellular immune responses to IBV vaccine. Moreover, the viral loads in the NC8-ChIL17B- and IBV-vaccinated group were significantly lower than in the control groups, suggesting a significant promotion of the immunoprotection of IBV vaccination against the virulent IBV strain. Therefore, ChIL-17B is a promising, effective adjuvant candidate for chicken virus vaccines.

Increased AT2R expression is induced by AT1R autoantibody via two axes, Klf-5/IRF-1 and circErbB4/miR-29a-5p, to promote VSMC migration.

Vascular remodeling can be caused by angiotensin II type 1 receptor (AT1R) autoantibody (AT1-AA), although the related mechanism remains unknown. Angiotensin II type 2 receptor (AT2R) plays multiple roles in vascular remodeling through cross-talk with AT1R in the cytoplasm. Here, we aimed to explore the role and mechanism of AT2R in AT1-AA-induced vascular smooth muscle cell (VSMC) migration, which is a key event in vascular remodeling. In vitro and in vivo, we found that AT2R can promote VSMC migration in AT1-AA-induced vascular remodeling. Moreover, AT2R expression was upregulated via Klf-5/IRF-1-mediated transcriptional and circErbB4/miR-29a-5p-mediated posttranscriptional mechanisms in response to AT1-AA. Our data provide a molecular basis for AT1-AA-induced AT2R expression by transcription factors, namely, a circular RNA and a microRNA, and showed that AT2R participated in AT1-AA-induced VSMC migration during the development of vascular remodeling. AT2R may be a potential target for the treatment of AT1-AA-induced vascular diseases.

Pharmacokinetic interaction between a Chinese herbal formula Huosu Yangwei oral liquid and apatinib in vitro and in vivo.

OBJECTIVES: This study aimed to evaluate the inhibitory effects of Huosu Yangwei oral liquid (HSYW) on cytochrome P450 enzymes (CYPs) and to investigate whether this herbal medicine could modulate the pharmacokinetic behaviour of the co-administered CYP-substrate drug apatinib. METHODS: Cytochrome P450 enzymes inhibition assays were conducted in human liver microsomes (HLM) by a LC-MS/MS method for simultaneous determination of the oxidative metabolites of eight probe substrates for hepatic CYPs. The modulatory effects of HSYW on the oxidative metabolism of apatinib were investigated in both HLM and rat liver microsomes (RLM). The influences of HSYW on the pharmacokinetic behaviour of apatinib were investigated in rats. KEY FINDINGS: Huosu Yangwei oral liquid inhibited all tested CYPs in human liver preparations, with the IC50 values ranged from 0.3148 to 2.642 mg/ml. HSYW could also inhibit the formation of two major oxidative metabolites of apatinib in liver microsomes from both human and rat. In-vivo assays demonstrated that HSYW could significantly prolong the plasma half-life of apatinib by 7.4-fold and increase the AUC0-inf (nm·h) of apatinib by 43%, when HSYW (10 ml/kg) was co-administered with apatinib (10 mg/kg) in rats. CONCLUSIONS: Huosu Yangwei oral liquid could inhibit mammalian CYPs and modulated the metabolic half-life of apatinib both in vitro and in vivo.

Long non-coding RNA colon cancer-associated transcript-1 regulates tumor cell proliferation and invasion of non-small-cell lung cancer through suppressing miR-152.

AIM: Lung cancer serves as one of the most common cancers in the world, and approximately 50% of non-small-cell lung cancer (NSCLC) patients are found to be aged >70 when diagnosed. In this study, we aimed to explore the effect of long non-coding RNAs colon cancer-associated transcript-1 (CCAT1) in NSCLC. METHODS: A total of 72 clinical samples from older NSCLC patients were collected for analysis. The relative mRNA level of CCAT1 was detected through real-time polymerase chain reaction. Overall survival of NSCLC patients was detected through Kaplan-Meier survival analysis. MTT assays were used to detect cell proliferation. Cell invasion was determined by transwell assay. Protein levels were detected through western blot. RESULTS: CCAT1 expression levels significantly increased in NSCLC tumor tissues and were associated with poor overall survival of NSCLC patients. CCAT1 promotes cell proliferation, cell invasion and epithelial-mesenchymal transition of NSCLC cell lines. CCAT1 binds with miR-152, and the effect of si-CCAT1 in NSCLC cell proliferation, cell invasion and epithelial-mesenchymal transition was partially reversed by anti-miR-152. CONCLUSIONS: Long non-coding RNA CCAT1 regulates tumor cell proliferation and invasion in NSCLC through suppressing miR-152. Geriatr Gerontol Int 2020; ••: ••-••.

Understanding the emission pattern and source contribution of hazardous air pollutants from open burning of municipal solid waste in China.

The open burning of municipal solid waste (MSW) is common in China. Therein, low-temperature anoxic combustion results in the emission of hazardous air pollutants. This study employed a dilution sampling system to conduct open burning testing on MSW samples from different functional urban areas. Additionally, modified combustion efficiency was used to distinguish smoldering and flaming combustion in two of the most common open burning practices in China: pile-up burning and barrel burning. The sampled pollutants included gaseous pollutants (e.g., CO2, CO, SO2, and NOx) and fine particles (PM2.5). This study also analyzed the carbonization compounds, 9 water-soluble ions, and 8 toxic heavy metals in PM2.5. Emission factors of air pollutants from open burning of different MSW compositions and burning modes were determined. The composition of PM2.5 from MSW open burning comprised average 43.9%, 22.5%, and 0.4% of organic carbon (OC), water-soluble ions, and toxic heavy metals (THMs), respectively. OC was found to be the primary component of PM2.5. Based on localized emission factor database, the emissions and source contribution of open burning of MSW in China were quantified. The open burning of MSW can contribute averaged 8.7%, 16.7%, 3.8%, 1.3% of PM2.5, OC, THMs, and gaseous air pollutants of reported emissions of anthropogenic sources, respectively. This work can complement current anthropogenic emission inventory and assist policy-making.

[Characteristics of Heavy Metal Pollutants of PM2.5 from Open Burning of Municipal Solid Waste (MSW) and the Associated Exposure Health Risks].

The characteristics and health risk assessment for heavy metal pollutants in PM2.5 discharged from the open burning of municipal solid waste (MSW) in different functional areas were studied using a flue gas diluted sampling system. The two common open burning modes of barrel and natural pile-up burning were considered. The results show that the concentration of zinc (Zn) was the highest among the heavy metals produced by five different components of waste incineration, ranging from 1324.03 to 3703.12 mg·kg-1. The concentration of cadmium (Cd) was the lowest, ranging from 20.25 to 63.68 mg·kg-1. According to the geo-accumulation index, lead (Pb), Zn, arsenic (As), and Cd were highly polluted in the measured MSW samples, and all four of these metals reached moderate or higher levels of pollution under natural pile-up burning methods. The geo-accumulation index of Cd was much higher than 5. The results of the human health risk assessment showed that non-carcinogenic risk values for 8 heavy metals (Pb, Zn, Cu, Mn, As, Cd, Cr, and Ni) by respiratory exposure were less than 1, which is within the safe range. For natural pile-up burning, the total non-carcinogenic risk values for As and Pb for children were higher than 1, indicating a non-carcinogenic risk. The carcinogenic risk values for four carcinogenic elements (As, Cd, Cr, and Ni) were less than 1.0×10-4, but still represented a low potential carcinogenic risk under exposure for long periods of time.

Autoantibodies against AT1 Receptor Contribute to Vascular Aging and Endothelial Cell Senescence.

Vascular aging predisposes the elderly to the progression of many aging-related vascular disorders and leads to deterioration of cardiovascular diseases (CVD). However, the underlying mechanisms have not been clearly elucidated. Agonistic autoantibodies against angiotensin II type 1 (AT1) receptor (AT1-AAs) have been demonstrated to be pro-inflammatory and contribute to the progression of atherosclerosis. However, the association between AT1-AAs and vascular aging has not been defined. Peripheral arterial disease (PAD) is an acknowledged vascular aging-related disease. In this study, AT1-AAs were detected in the sera of patients with PAD and the positive rate was 44.44% (n=63) vs. 17.46% in non-PAD volunteers (n=63). In addition, case-control analysis showed that AT1-AAs level was positively correlated with PAD. To reveal the causal relationship between AT1-AAs and vascular aging, an AT1-AAs-positive rat model was established by active immunization. The carotid pulse wave velocity was higher, and the aortic endothelium-dependent vasodilatation was attenuated significantly in the immunized rats. Morphological staining showed thickening of the aortic wall. Histological examination showed that levels of the senescent markers were increased in the aortic tissue, mostly located at the endothelium. In addition, purified AT1-AAs-IgGs from both the immunized rats and PAD patients induced premature senescence in cultured human umbilical vein endothelial cells. These effects were significantly blocked by the AT1 receptor blocker. Taken together, our study demonstrates that AT1-AAs contribute to the progression of vascular aging and induce EC senescence through AT1 receptor. AT1-AA is a novel biomarker of vascular aging and aging-related CVD that acts to accelerate EC senescence.