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Microneedle (MN) patches consist of a hydrogel-forming MN array and a drug-containing reservoir. Drug-containing reservoirs documented in the literature include polymeric films and lyophilized wafers. While effective, both reservoir formulations are aqueous based, and so degradation can occur during formulation and drying for drugs inherently unstable in aqueous media. The preparation and characterization of novel, nonaqueous-based, directly compressed tablets (DCTs) for use in combination with hydrogel-forming MN arrays are described for the first time. In this work, a range of drug molecules are investigated. Precipitation of amoxicillin (AMX) and primaquine (PQ) in conventional hydrogel-forming MN arrays leads to use of poly(vinyl alcohol)-based MN arrays. Following in vitro permeation studies, in vivo pharmacokinetic studies are conducted in rats with MN patches containing AMX, levodopa/carbidopa (LD/CD), and levofloxacin (LVX). Therapeutically relevant concentrations of AMX (≥2 µg mL-1 ), LD (≥0.5 µg mL-1 ), and LVX (≥0.2 µg mL-1 ) are successfully achieved at 1, 2, and 1 h, respectively. Thus, the use of DCTs offers promise to expand the range of drug molecules that can be delivered transdermally using MN patches.

A novel carbon quantum dots (CQDs) were successfully synthesized by one-step hydrothermal reaction using Rosa roxburghii as a biomass-based precursor. The CQDs have an average size of 2.5 nm and a narrow size distribution. They display strong blue fluorescence with a quantum yield of 24.8% and good biocompatibility. Notably, these CQDs were capable of detecting trace o-nitrophenol in surface water and sewage with high sensitivity and specificity. The linear range is 0.08-40 μmol/L, and the limit of detection is 15.2 nmol/L. Furthermore, this CQDs was successfully applied for o-nitrophenol analysis in river water and sewage samples. Additionally, Hep3B cells, a human hepatocellular carcinoma cell line, can be easily imaged with high resolution using the as-prepared CQDs as nanoprobes. These results reveal that the as-prepared CQDs have potential applications for detecting o-nitrophenol and cell imaging.

Hepatic stem cell transplantation has been demonstrated as an effective alternative therapy for the end-stage liver failure patients. Therefore, the functional detection of hepatic stem cell is essentially required. The present study confirmed that adenovirus BMP9 (Ad-BMP9) could increase the ALB-Gluc activity of HP14-19 hepatic progenitor cells, the expression of specific hepatic markers ALB, TAT, UGT1A were up-regulated while the hepatic stem cell markers DLK, AFP were down-regulated, and the number of positive Periodic acid-Schiff (PAS) stained cells were significantly higher than those in control group. However, the indocyanine green (ICG) uptake failed to be detectable in induced hepatocytes, which was inconsistent. By using another cell line LC14d, we found out that positive ICG uptake cells were located in the area of low cell density, while positive PAS stained cells were mainly concentrated in the area where cells were overlapped, indicating that different cell confluence might affect the outcomes of ICG uptake and PAS staining. A manual wound healing of Ad-BMP9 induced HP14-19 cells was made, the crawling cells were stained positive for ICG but not for PAS. Therefore, our finding may provide evidence for better application of PAS staining and ICG uptake assay in functional detection of mature hepatocytes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-021-00453-8.

Several clinical therapies such as tissue repair by replacing injured tissues with functional ones have been reported; however, there is great potential for exploring traditional herbal-induced regeneration with good safety. Tongqiao Huoxue Decoction (TQHXD), a well-known classical traditional Chinese medicinal formula, has been widely used for clinical treatment of stroke. However, biological activity and mechanisms of action of its constituents toward conferring protection against cerebral ischemia-reperfusion (I/R) injury remain unclear. In this present study, we evaluated TQHXD quality using HPLC; then, it was screened for its potential active ingredients using a series of indices, such as their drug-likeness and oral bioavailability. Subsequently, we analyzed the potential mechanisms of TQHXD anti-I/R using gene ontology functional enrichment analyses. The network pharmacological approach enabled us to screen 265 common targets associated with I/R, indicating that TQHXD had remarkable protective effects on infarction volume, neurological function scores, and blood-brain barrier (BBB) injury. In addition, TQHXD significantly promoted the recovery of regional cerebral blood flow (rCBF) 7 days after reperfusion compared to rats in the vehicle group. Immunofluorescence results revealed a significantly higher CD34 expression in TQHXD-treated rats 7 days after reperfusion. TQHXD is not merely effective but eventually develops a secretory profile composed of VEGF and cerebral blood flow, a typical signature termed the angiogenesis-associated phenotype. Mechanistically, our data revealed that TQHXD (6 g/kg) treatment resulted in a marked increase in expression of p-focal adhesion kinase (FAK) and p-Paxillin proteins. However, Ki8751-mediated inhibition of VEGFR2 activity repealed its angiogenesis and protective effects and decreased both p-FAK and p-Paxillin protein levels. Taken together, these findings affirmed the potential of TQHXD as a drug for the management of stroke, which might be exerted by increasing the angiogenesis via the VEGF pathway. Therefore, these results provide proof-of-concept evidence that angiogenesis is a major contributor to TQHXD-treated I/R and that TQHXD is a promising traditional ethnic medicine for the management of this condition.

Natural products with high antioxidant activity have attracted great attention in recent years. A water extraction and alcohol precipitation method were used to extract polysaccharides from the Flammulina velutipes stem-base (FVSP). The series of samples including FVSP30, FVSP45, FVSP60, and FVSP75 were isolated by different concentrations of ethanol. The crude polysaccharides were purified by freeze-thaw; deproteinization; DEAE cellulose-52 chromatography; Sephadex G-100 size-exclusion chromatography; and another series of samples were found including FVSP-1, FVSP-2, and FVSP-3. Through 2,2-diphenyl-1-picrylhydrazyl, hydroxyl radical, and superoxide anion scavenging experiments, the effects of ethanol concentration during isolation and the degree of purification on the in vitro antioxidant properties of the FVSPs were analyzed. The results showed that the polysaccharides isolated by different ethanol concentrations exhibited strong antioxidant activity. With increasing ethanol concentration in the isolation process, the antioxidant activity was progressively enhanced. In the experimental concentration range, FVSP75 showed the strongest antioxidant activity at a concentration of 1.0 mg/mL. The FVSPs of different purities exhibited excellent antioxidant activity. Within the experimental range, as the degree of purification of the polysaccharides increased, the antioxidant activity decreased accordingly. FVSP-1, with low purity, exhibited the highest antioxidant activity at a concentration of 1.0 mg/mL. These results should provide a foundation for the use of FVSPs as a nutritional functional food or food additive and provide a theoretical basis for the efficient use of FVSPs.

The root cell wall is the first and primary target of aluminum (Al) toxicity. Monocots such as rice (Oryza sativa) can accumulate appreciable levels of hydroxycinnamic acids (HCAs) to modify and cross-link hemicellulose and/or lignin of the cell wall. Nevertheless, it is unclear whether this HCA-mediated modification of the cell wall is important for Al accumulation and resistance. We previously isolated and characterized a rice ral1 (resistance to aluminum 1) mutant that shows enhanced Al resistance. In this study, we cloned RAL1 and found that it encodes the 4-coumarate:coenzyme A ligase 4CL4, an enzyme putatively involved in lignin biosynthesis. Mutation of RAL1/4CL4 reduces lignin content and increases the accumulation of its substrates 4-coumaric acid (PA) and ferulic acid (FA). We demonstrate that altered lignin accumulation is not required for the enhanced Al resistance in ral1/4cl4 mutants. We found that the increased accumulation of PA and FA can reduce Al binding to hemicellulose and consequently enhance Al resistance in ral1/4cl4 mutants. Al stress is able to trigger PA and FA accumulation, which is likely caused by the repression of the expression of RAL1/4CL4 and its homologous genes. Our results thus reveal that Al-induced PA and FA accumulation is actively and positively involved in Al resistance in rice through the modification of the cell wall and thereby the reduced Al binding to the cell wall.

Pullulan was successfully esterified with octenyl succinic anhydride (OSA) in aqueous alkaline solutions. The degree of substitution (DS) was regulated from 0.0163, 0.0346 to 0.0469 by changing the OSA concentration (3.0%, 6.0% and 9.0%, respectively). Meanwhile, the weight-average molecular weight (Mw) of OSA-pullulans varied from 2.050 × 105, 2.113 × 105 to 2.124 × 105. The chemical structures of OSA-pullulans were characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance spectroscopy (1H NMR), which indicated that OSA groups were successfully grafted into pullulan. The surface tension, interfacial tension and droplet size of the emulsions stabilized by OSA-pullulans significantly reduced with the increase of DS. Furthermore, the emulsion stability (ES) and viscosity dramatically increased with DS compared with those of emulsion stabilized by pullulan. These results indicated emulsifying properties of OSA-pullulans were improved by increasing DS. Additionally, OSA-pullulans had excellent emulsion stability when DS was higher than 0.0346.

Isoorientin (ISO), a natural flavonoid compound, has been identified in several plants and its biological activity is determined and the study on lowering uric acid has not been reported. In view of the current status of treatment of hyperuricemia, we evaluated the hypouricemic effects of ISO in vivo and in vitro, and explored the underlying mechanisms. Yeast extract-induced hyperuricemia animal model as well as hypoxanthine and xanthine oxidase (XOD) co-induced high uric acid L-O2 cell model and enzymatic experiments in vitro were selected. The XOD activity and uric acid (UA) level were inhibited after the treatment of ISO in vitro and in vivo. Furthermore, serum creatinine (CRE) and blood urea nitrogen (BUN) levels were also significantly reduced and liver damage was recovered in pathological histology after the ISO administration in hyperuricemia animal model. The results of mechanism illustrated that protein expressions such as XOD, toll-like receptor 4 (TLR4), cathepsin B (CTSB), NLRP3, and its downstream caspase-1 as well as interleukin-18 (IL-18) were markedly downregulated by ISO intervention in vitro and in vivo. Our results suggest that ISO exerts a urate-lowering effect through inhibiting XOD activity and regulating TLR4-NLRP3 inflammasome signal pathway, thus representing a promising candidate therapeutic agent for hyperuricemia. Both animal models and in vitro experiments suggested that ISO may effectively lower uric acid produce. The mechanism might be the inhibition of XOD activity and NLRP3 inflammasome of upregulation.

Upon contact with biofluids, proteins are quickly adsorbed onto the nanoparticle (NP) surface to form a protein corona, which initiates the opsonization and facilitates the rapid clearance of the NP by macrophage uptake. Although polyethylene glycol (PEG) functionalization has been the standard approach to evade macrophage uptake by reducing protein adsorption, it cannot fully eliminate nonspecific uptake. Herein, polyglycerol (PG) grafting is demonstrated as a better alternative to PEG. NPs of various size and material were grafted with PG and PEG at 30, 20, and 10 wt % contents by controlling the reaction conditions, and the resulting NP-PG and NP-PEG were characterized qualitatively by IR spectroscopy and quantitatively by thermogravimetric analysis. Their resistivity to adsorption of the proteins in fetal bovine serum and human plasma were compared by polyacrylamide gel electrophoresis, bicinchoninic acid assay, and liquid chromatography-tandem mass spectrometry, giving a consistent conclusion that PG shields protein adsorption more efficiently than does PEG. The macrophage uptake was assayed by transmission electron microscopy and by extinction spectroscopy or inductively coupled plasma mass spectrometry, revealing that PG avoids macrophage uptake more efficiently than does PEG. In particular, a NP coated with PG at 30 wt % (NP-PG-h) prevents corona formation almost completely, regardless of NP size and core material, leading to the complete evasion of macrophage uptake. Our findings demonstrate that PG grafting is a promising strategy in nanomedicine to improve anti-biofouling property and stealth efficiency in nanoformulations.

Seven extraction methods, including hot water extraction (HWE), pressurized water extraction (PWE), ultrasound-assisted extraction, microwave-assisted extraction, ultrasound-assisted enzymatic extraction, high-speed shearing homogenization extraction, and ultrasound-microwave-assisted extraction, were utilized to extract polyphenolic-protein-polysaccharide complexes (PPPs) from Hovenia dulcis. Next, their physicochemical properties and in vitro antioxidant activities, antiglycation effects, and inhibition activities on &alpha, glucosidase and &alpha, amylase were studied and compared. The findings from this study indicate that various extraction processes exhibit notable influences on the physicochemical properties and in vitro bioactivities of PPPs. Extraction yields, contents of polyphenolics and flavonoids, apparent viscosities, molecular weights, molar ratios of monosaccharide compositions, and ratios of amino acid compositions in PPPs varied in different extraction methods. Furthermore, 13 phenolic compounds in PPPs, including rutin, myricitrin, myricetin, quercetin, kaempferol, protocatechuic acid, gallocatechin, p-hydroxybenzoic acid, ampelopsin, quercetin-7,4&prime, diglucoside, dihydroquercetin, 5-methylmyricetin, and naringenin, were identified. The relatively strong in vitro antioxidant activities, antiglycation effects, and inhibition activities on &alpha, amylase were determined in both PPP-W and PPP-P obtained by HWE and PWE, respectively. The high content of total polyphenolics may be one of the main contributors to their in vitro bioactivities. The findings have shown that the PWE method can be an appropriate method to prepare PPPs with strong bioactivities for application in the functional food industry.

Ciliates are important components in planktonic food webs, but our understanding of their community structures in different oceanic water masses is limited. We report pelagic ciliate community characteristics in three seas: the tropical West Pacific, the Bering Sea and the Arctic Ocean. Planktonic ciliate abundance had “bimodal-peak”, “surface-peak” and “DCM (deep chlorophyll a maximum layer)-peak” vertical distribution patterns in the tropical West Pacific, the Bering Sea and the Arctic Ocean, respectively. The abundance proportion of tintinnid to total ciliate in the Bering Sea (42.6%) was higher than both the tropical West Pacific (7.8%) and the Arctic Ocean (2.0%). The abundance proportion of small aloricate ciliates (10–20 µm size-fraction) in the tropical West Pacific was highest in these three seas. The Arctic Ocean had higher abundance proportion of tintinnids in larger LOD (lorica oral diameter) size-class. Proportion of redundant species increased from the Arctic Ocean to the tropical West Pacific. Our result provided useful data to further understand ecology roles of planktonic ciliates in different marine habitats.

BackgroundElderly patients with diffuse large B-cell lymphoma (DLBCL) present with poor clinical outcome and intolerance to intensive chemotherapy. Histone deacetylase inhibitors (HDACIs) show anti-lymphoma activities and can be applied to treat DLBCL. This study aimed to evaluate efficacy and safety of oral HDACI tucidinostat (formerly known as chidamide) plus R-CHOP (CR-CHOP) in elderly patients with newly diagnosed DLBCL (International Prognostic Index ≥ 2).ResultsAmong 49 patients, the complete response rate was 86%, with overall response rate achieving 94%. The 2-year progression survival (PFS) and overall survival (OS) rates were 68% (95% CI 52–79) and 83% (95% CI 68–91). Comparing with historical control (NCT01852435), the 2-year PFS and OS rates of double-expressor lymphoma phenotype (DEL) were improved, and negative prognostic effect of histone acetyltransferasesCREBBP/EP300mutations was also mitigated by CR-CHOP. Grade 3–4 neutropenia was reported in 171, grade 3–4 thrombocytopenia in 27, and grade 3 anemia in 11 of 283 cycles. No grade 4 non-hematological adverse event was reported.ConclusionCR-CHOP is effective and safe in elderly patients with newly diagnosed DLBCL. Relevance of DEL phenotype and molecular biomarkers on CR-CHOP response warrants further investigation in DLBCL.Trial registrationClinicalTrial.gov, NCT02753647. Registered on April 28, 2016.

5-methoxycanthin-6-one, a major canthinone alkaloid isolated from Picrasma quassioides, exhibited significant pharmacological activities. In this study, a rapid and sensitive LC-MS/MS method was established and validated for the determination of 5-hydroxy-4-methoxycanthin-6-one in rat plasma. Small quantities (20 μL) of plasma sample were used for sample preparation. 5-Hydroxy-4-methoxycanthin-6-one and an internal standard (IS, caffeine) were separated using an ACQUITY HSS T3 column (50 × 2.1 mm, 1.7 μm; Waters, Milford, MA, USA). The mobile phase was composed of 0.1% formic acid in water and acetonitrile. Precursor-to-product ion transitions were m/z 267.0 → 168.2 and m/z 195.0 → 138.1 for quantitative monitoring of 5-hydroxy-4-methoxycanthin-6-one and IS, respectively. The assay was linear over the concentration range of 0.5-500 ng/mL (r > 0.99) with the lower limit of quantification 0.5 ng/mL. Other parameters, including intra- and inter-day precision and accuracy, carryover, stability, extraction recovery, matrix effect, and dilution effect, were within acceptable limits. The validated method was successfully applied to pharmacokinetic study in rats after intravenous (5 mg/kg) and oral (10, 25, 50 mg/kg) administration of 5-hydroxy-4-methoxycanthin-6-one. The result indicated that 5-hydroxy-4-methoxycanthin-6-one was quickly absorbed into the blood and reached the highest concentration at ~33.0-42.0 min, with moderate elimination half-life (0.85-2.11 h) and low bioavailability (16.62-24.42%) after oral administration. The study provided valuable information that can be used as a reference for studying other canthinone alkaloids.

To investigate the hormone-like activities of Kuntai capsule (KTC) in the uteri of ovariectomized rats and immature rabbits.Following bilateral ovariectomy, rats were randomly divided into six groups including sham group, control group, estradiol valerate group, KTC 0.24, 0.6, and 1.5 g/kg groups. The rats were treated with 0.5% CMC-Na, estradiol valerate and KTC (0.24, 0.6, and 1.5 g/kg), respectively for 28 consecutive days. Then the estrous cycle, uterine changes and pathological changes were examined. Serum levels of estradiol (E2), and progesterone (P4) were measured by enzyme-linked immunosorbent assay (ELISA). Protein levels of estradiol receptor (ER), progesterone receptor (PR), vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA) and nuclear-associated antigen-67 (Ki-67) in uterine tissues were detected by western blot. Immature rabbits were estrogen-primed prior to intragastric administration with KTC for 6 d consecutively. Then, the uteri underwent hematoxylin-eosin staining to observe endometrial transformation.Compared with the control group, 0.6 and 1.5 g/kg KTC markedly decreased the uterine organ coefficient and endometrial thickness (P0.05). The serum level of P4 was increased in the KTC 0.6 g/kg group (P0.05). There were no significant variations in the serum level of E2 in the KTC groups compared with the control group. ER¦Â, but not ER¦Á, was markedly upregulated after KTC administration (P0.05). Furthermore, 1.5 g/kg KTC significantly decreased the protein level of PRA (P0.05) and 0.6 g/kg KTC increased the protein level of PRB in the uteri (P0.05). VEGF was highly expressed after treatment with 0.24 and 0.6 g/kg KTC, and Ki-67 was markedly reduced in ovariectomized rats treated with 1.5 g/kg KTC. No difference was found in the expression of PCNA. KTC 0.24 and 0.6 g/kg promoted endometrial transformation in immature rabbit uteri.KTC does not demonstrate obvious estrogen-like effect on uteri after ovariectomy, but it does exhibit weak progestogen-like effect, by which mechanism of action is yet to be further investigated.

The dynamic process of synthesizing Janus nanoparticles (JNPs) at a water/oil two-phase interface using a grafting-from reaction is investigated via dissipative particle dynamics simulations. We find that the interfacial tension, the initial monomer concentration, and the reaction probability can greatly influence the microscopic characteristics of JNP structure. It is difficult to synthesize a symmetric JNP with an equal volume ratio between hydrophilic and hydrophobic parts by grafting-from methods unless the physical chemical conditions in the two phases are strictly symmetric, and there is always a disordered domain on the JNP at a two immiscible solvents interface. Interestingly, for certain routes for synthesizing JNPs with a grafting-from method, the higher interfacial tension between the water and oil phases may enhance the degree of disorder of the grafted chains. The asymmetric initial monomer concentration in solution and the reaction probability can be used to control the syntheses of asymmetric JNPs.

Ethnopharmacological relevance Alstonia scholaris (L.) R. Br. (Apocynaceae) is a medicinal plant in China traditionally used to treat pulmonary diseases, including bronchitis, whooping cough, asthma and chronic obstructive pulmonary disease. Aim of the study To provide experimental data supporting clinical adaptation of total indole alkaloids ( TA) from A. scholaris leaves for treating emphysema. Materials and methods An emphysema model was induced by a single intratracheal instillation of porcine pancreatic elastase followed by administration of TA and four main alkaloid components (scholaricine, 19-epischolaricine, vallesamine, and picrinine) for 30 consecutive days. Cytokine levels, histopathological parameters and protein expression in lung tissues were examined. Results Administering the TA, picrinine, scholaricine, 19-epischolaricine and vallesamine for 30 days effectively inhibited inflammatory cell accumulation and invasion in the lung tissue and relieved pulmonary tissue injury. Oxygen saturation was enhanced, and interleukin (IL)-1β, monocyte-chemo attractive peptide 1, IL-11, matrix metalloproteinase-12, transforming growth factor-β and vascular endothelial growth factor levels were significantly reduced, likely by suppressing overactivation of alveolar macrophages and pulmonary fibrosis. The elastin content was markedly elevated, and fibronectin was reduced. Bcl-2 expression was significantly increased, and nuclear factor-κB and β-catenin levels were decreased. Conclusions TA can be potentially used as an effective novel drug for pulmonary emphysema and exerts its effects through not only inhibiting inflammation of the airway wall and airflow resistance but also promoting lung elastic recoil and protease/anti-protease balance.

Hypoxia is a key concern during the treatment of non-small cell lung cancer (NSCLC), and hypoxia-inducible factor 1 alpha (HIF-1α) has been associated with increased tumor resistance to therapeutic modalities such as cisplatin. Compensatory activation of nucleotide excision repair (NER) pathway is the major mechanism that accounts for cisplatin resistance. In the present study, we suggest a novel strategy to improve the treatment of NSCLC and overcome the hypoxia-induced cisplatin resistance by cotreatment with Oroxylin A, one of the main bioactive flavonoids of Scutellariae radix. Based on the preliminary screening, we found that xeroderma pigmentosum group C (XPC), an important DNA damage recognition protein involved in NER, dramatically increased in hypoxic condition and contributed to hypoxia-induced cisplatin resistance. Further data suggested that Oroxylin A significantly reversed the hypoxia-induced cisplatin resistance through directly binding to HIF-1α bHLH-PAS domain and blocking its binding to HRE3 transcription factor binding sites on XPC promoter which is important to hypoxia-induced XPC transcription. Taken together, our findings not only demonstrate a crucial role of XPC dependent NER in hypoxia-induced cisplatin resistance, but also suggest a previously unrecognized tumor suppressive mechanism of Oroxylin A in NSCLC which through sensitization of cisplatin-mediated growth inhibition and apoptosis under hypoxia.

In various autoimmune diseases, Galecin-9 (Gal-9) has been shown to regulate the T-cell balance by decreasing Th1 and Th17, while increasing the number of regulatory T cells (Tregs). However, the role of Gal-9 in the patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD) remains unclear. This study aims to measure the Gal-9 levels in serum and peripheral blood mononuclear cells (PBMCs) in patients with ACS plus CKD and examine their clinical implication. The serum levels of Gal-9 were determined by enzyme-linked immunosorbent assay (ELISA), the expression levels of Gal-9, Tim-3, and Foxp3 mRNA in PBMCs were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR), and the expression of Gal-9 on the surface of PBMCs and in PBMCs was analyzed by flow cytometry. Furthermore, the correlation of serum Gal-9 levels with anthropometric and biochemical variables in patients with ACS plus CKD was analyzed. The lowest levels of Gal-9 in serum and PBMCs were found in the only ACS group, followed by the ACS+CKD group, and the normal coronary artery (NCA) group, respectively. Serum Gal-9 levels were increased along with the progression of glomerular filtration rate (GFR) categories of G1 to G4. Additionally, serum Gal-9 levels were negatively correlated with high-sensitivity C-reactive protein (hs-CRP), estimated GFR (eGFR), and lipoprotein(a), but positively with creatinine, age, osmotic pressure, and blood urea nitrogen (BUN). Notably, serum Gal-9 was independently associated with hs-CRP, osmotic pressure, and lipoprotein(a). Furthermore, serum Gal-9 levels were elevated in patients with type 2 diabetes (T2DM) and impaired glucose tolerance (IGT) in ACS group. It was suggested that the levels of Gal-9 in serum and PBMCs were decreased in patients with simple ACS and those with ACS plus CKD, and hs-CRP, eGFR, osmotic pressure and T2DM may have an influence on serum Gal-9 levels.

Background: Elderly patients with diffuse large B-cell lymphoma (DLBCL) present with poor clinical outcome and intolerance to intensive chemotherapy. Histone deacetylase inhibitors (HDACIs) show anti-lymphoma activities and can be combined with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in treating DLBCL. Methods: Elderly patients with newly diagnosed DLBCL (IPI≥2) received oral HDACI chidamide (20mg twice a week for two weeks) and R-CHOP every 21 days (CR-CHOP) for six cycles. The primary endpoint was complete response rate at the end of the treatment. Whole exome sequencing, targeted sequencing and RNA-sequencing were performed in patients with available tumor samples. Findings: Among 49 patients, the complete response rate was 86%, with overall response rate achieving 94%. 2-year PFS and OS rate were 68% (95%CI 52-80) and 80% (95%CI 64-90), respectively. There was no difference in 2-year PFS (83% vs 65%, P=0.210) or OS (91% vs 81%, P=0.313) rate between double-expressor lymphoma (DEL) and non-DEL phenotype. However, 2-year PFS and OS rate of DEL patients was significantly improved by CR-CHOP, comparing with historical control (NCT01852435, P=0.030 and 0.036). Instead of histone acetyltransferases CREBBP / EP300 , histone methyltransferases KMT2D mutations were associated with inferior PFS and OS (P=0.043 and

An amphiphilic cholesteryl-derived diphenylalanine (Chol-FF) has been developed, which can emulsify the EDA/water (from 9-1 to 1-9, v/v) mixed solutions. External shaking or aging induced a transition of the Chol-FF EDA/water (9-1) system from emulsion to gel. Micron-sized fibers were observed in the gel system, and the formation was driven by the combination of intermolecular π-π stacking, hydrogen bonding, and van der Waals forces based on several spectroscopic studies. A lamellar packing mode was adopted by Chol-FF molecules in the gel. Moreover, the transition from emulsion to gel can be reversed by heating-cooling treatment due to the non-covalent driving nature.

Purpose. Recent research has provided novel insight into the function of fibromodulin (FMOD) in wound healing and angiogenesis. The role of FMOD in initiation of proliferative vitreoretinopathy (PVR) has not been studied. This study investigated the effect of FMOD on human retinal pigment epithelial (RPE) cell, which plays an essential role in the progression of PVR, and the possible mechanisms. Methods. Small interfering (si) RNA-based gene transfer technology was used to decrease FMOD expression and to study its effects on RPEs in vitro. Cell Counting Kit-8 assays, transwells, and flow cytometry analysis were used to measure cell proliferation, migration, cell cycle, and apoptosis. Western blot was used to measure expression of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), extracellular signal-related kinase 1/2 (ERK1/2), and phosphoinositide 3 kinase (PI3K/AKT). Results. After transfection of RPEs with a FMOD-specific siRNA, cell proliferation and migration were inhibited to the percentage of 65% ± 5% and 39% ± 10%, respectively, compared to the control group. Depletion of FMOD induced cell cycle arrest and apoptosis in RPE cells. Downregulation of VEGF, VEGFR2, and phosphorylated AKT (p-AKT) were detected in transfected RPEs. Conclusion. Depletion of FMOD selectively downregulated the expression of VEGF and VEGFR2 and inhibited the signaling pathway of AKT phosphorylation, which consequently inhibited the proliferation and migration of RPE Cell.

Chitin deacetylases (CDAs) are enzymes that catalyze the conversion of chitin into chitosan, thereby influence the mechanical and permeability properties of structures such as the cuticle and peritrophic matrices. The full length cDNAs of chitin deacetylase2 (CDA2) genes from Hyphantria cunea were fully cloned by PCR amplification. Two cDNA sequences of HcCDA2 were searched from transcriptome of H. cunea and named as HcCDA2a and HcCDA2b. The deduced protein sequences showed that HaCDA2a and HaCDA2b are synthesized as preproteins of 524 and 518 amino acid residues with an 18-amino acid signal peptide, respectively. HcCDA2a and HcCDA2b contained a chitin-binding domain (ChBD), a low-density lipoprotein receptor class A domain (LDLa) and a polysaccharide deacetylase-like catalytic domain (CDA). Gene expression analyses results showed that HcCDA2a and HcCDA2b were both expressed at the head, integument, foregut, midgut, hindgut, Malpighian tubules and fat body, as well as the 1st to 5th days of fifth instar larvae. Western blot analyses revealed that HcCDA2 protein was highly abundant in the head and integument, and the developmental expression result in the fifth instars showed that HcCDA2 was highly present at the first two days. Besides, RT-PCR results showed that HcCDA2a and HcCDA2b were both expressed in integument and head, whether in molting stage or feeding stage. No visiable phenotypic changes were observed after injection of dsHcCDA2b, while lethal phenotypes of cuticle shedding failure and high mortality were resulted from injection of dsHcCDA2a. The silence of HcCDA2a leads to the ecdysis failure and death of H. cunea. These results suggest that HcCDA2 plays an important role during insect development, and provide new candidate targets and basis for developing environment-friendly pesticides.

Polyurethane elastomer electrolyte (PUEE) represents a promising class of polymer solid electrolytes for the preparation and packaging of flexible devices by anodic bonding. In this work, PUEEs were designed and prepared via a pre-polymerization method and cured at room temperature using polypropylene glycol (PPG), toluene-2,4-diisocyanate (TDI) and 1,4-butanediol (BDO) in the presence of varying amounts of lithium bis(trifluoromethanesulphonyl)imide (LiTFSI). All PUEEs exhibited high thermal stability and conductivity, with the highest ionic conductivity of 9.6 × 10−5 S cm−1 for PUEE6 (n[NHCOO]/Li+ = 1) at 55 °C. The results showed that LiTFSI was dissolved completely in the polyurethane matrix, and the complexing reactions occurred between the lithium ions and the polar groups of polyurethane. After that, the prepared PUEE and the Al sheet were successfully joined by the anodic bonding process. The microstructures of the bonded interface between PUEE and the Al sheet with a clear intermediate bonding layer could be observed in the cross-section scanning electron microscopy (SEM) images, and the elements in each layer were also detected by energy dispersive spectroscopy (EDS), which indicated that the PUEE and the Al sheet were bonded together. The maximum tensile strength for bonded PUEE6/Al was up to 0.45 MPa. All these results demonstrated that the prepared PUEE material would be a promising candidate for the preparation and packaging of flexible devices by anodic bonding.

"Curcumae Radix", the dried rhizomes of Curcuma kwangsiensis documented in Chinese pharmacopoeia, has been traditionally used for the treatment of inflammatory and pain diseases, such as jaundice and red urine, cleaning the heart-fire and depression, arthralgia, and dysmenorrhea. However, according to literature surveys, anti-inflammatory and antinociceptive studies of C. kwangsiensis have been seldom reported so far.The current study focuses on the anti-inflammatory and antinociceptive effects of C. kwangsiensis and discovering the bioactive compounds for its traditional usages both in vivo and in vitro, which could provide scientific justification about its traditional use.The anti-inflammatory and antinociceptive assays of various layers (ME, EA, AQS) from C. kwangsiensis were achieved by carrageenan-induced paw edema and acetic acid-induced writhing animal models, respectively. The most bioactive part, EA layer was further phytochemically investigated by multiple step chromatography techniques. The structures of these isolates were unambiguously elucidated by means of extensive spectroscopic and chemical methods, and comparison with corresponding data of the reported literature. Four major sesquiterpenoids (4, 6, 14, and 15) were achieved for their anti-inflammatory and antinociceptive assays by the two aforementioned animal models in vivo. All the isolated compounds were evaluated for their anti-inflammatory effects via detecting inflammatory mediator releases (COX-2, IL-1β, and TNF-α) in RAW 264.7 macrophage cells induced by LPS.The ME and EA layers significantly alleviated the paw edema caused by carrageenan and decreased the number of writhes induced by acetic acid at the dose of 200 and/or 100 mg/kg in comparison to the control group (p 0.01/0.05), and the EA layer exhibited better activity than that of ME layer. Subsequent phytochemical investigation on EA layer of C. kwangsiensis exhibited that three new terpenoid compounds (1-3), identified as (12Z,14R)-7β-hydroxylabda-8(17),12-diene-14,15,16-triol (1), (12Z,14S)- 7β-hydroxlabda-8(17),12-diene-14,15,16-triol (2), and (4S)-hydroxy-(8)-methoxy-(5S)-(H)-guaia1(10),7(11)-dien-12,8-olide (3), together with twenty-two known analogs were isolated. Furthermore, four major sesquiterpenoids (4, 6, 14, and 15) significantly relieved the paw edema and number of writhes at 100 and/or 50 mg/kg (p 0.05/0.01). Likewise, the majority of sesqui- and diterpenoids isolated could remarkably inhibited the secretion of inflammatory mediators (COX-2, IL-1β, and TNF-α) in LPS-stimulated RAW 264.7 macrophages cells at the concentration of 20 μg/mL, comparable to DXM used as the positive control. All the results suggested that EA layer from C. kwangsiensis possessed the anti-inflammatory and antinociceptive activities, and these sesqui- and diterpenoids could be the effective constituents responsible for relieving inflammation.The present studies undoubtedly determined the anti-inflammatory and antinociceptive material basis of C. kwangsiensis, including the EA layer and its precise components, which presented equivalent or better anti-inflammatory effects than that of positive control (ASP/DXM) in vivo and in vitro. These results not only would account for scientific knowledge for traditional use of C. kwangsiensis, but also provide credible theoretical foundation for the further development of anti-inflammatory and antinociceptive agents.

An in situ tracing study based on solid-phase microextraction (SPME) was conducted to investigate the uptake and elimination of organophosphorus pesticides in apples. A matrix-compatible polydimethylsiloxane/poly(styrene-co-divinylbenzene)/polydimethylsiloxane fiber was produced to meet the needs of in situ sampling. The fiber had high extraction ability, good sensitivity and accuracy with respect to the analytes in apple pulp, and could be used 85 times. Although the sampling rate was changing over time, quantification was still achieved by the sampling rate calibration method. Some factors that affect its applicability were studied. The limits of detection were 0.18 ng/g for diazinon and 0.20 ng/g for chlorpyrifos, rather lower than the maximum residue limits of the National Food Safety Standard of China (GB 2763-2016) and the European Commission (Reg.(EU) No 834/2013, 2018/686). The accuracy of in situ SPME quantification was verified by comparing with the results obtained by the traditional liquid&ndash, liquid extraction method. In this work, the in situ sampling method is developed using apples, diazinon, and chlorpyrifos as a model system, however, this method can be used for in vivo analysis of fruits and vegetables for nutrition and safety monitoring.

Three anthracen- or pyrene-based coumarin derivatives have been successfully synthesized and characterized by EA, IR and 1H NMR. The photophysical properties of all derivatives were investigated by UV-Vis and photoluminescence spectroscopic analysis. Their thermal stabilities were demonstrated by TGA. These compounds exhibit strong blue mission under ultraviolet light excitation and have potential possible to explore organic electroluminescent materials. The vacuum-processed doped devices with a configuration of ITO/TAPC (20 nm)/TBADN: b1 (x wt%, 30 nm)/TPBi (50 nm)/Liq (2 nm)/Al (150 nm) was fabricated, in which the devices based on b1 exhibited the best electroluminescence performance with a maximum brightness of 8165 cd/m2 and a maximum luminous efficiencies of 6.13 cd/A and a maximum external quantum efficiency (EQE) of 2.75%.

A novel actinobacterium, designated strain CFH 30205T, was isolated from a soil sample collected from a karst cave in Luoyang, Henan Province, China. The taxonomic position of the strain was investigated by using a polyphasic approach. Cells of the strain were aerobic, Gram-stain-positive, non-motile and rod-shaped. The strain was found to be catalase- and oxidase-positive. Strain CFH 30205T grew optimally at 28 °C, pH 9.0 and in the presence of up to 1.5 % NaCl (w/v). On the basis of 16S rRNA gene sequence analysis, strain CFH 30205T was most closely related to the type strains of Nocardioides terrigena DS-17T (97.6 % sequence similarity) and Nocardioides sediminis MSL-01T (97.0 %). The DNA G+C content was determined to be 69.9 mol%. ll-2,6-Diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The whole-cell sugars were mannose, xylose and galactose. The major isoprenoid quinone was MK-8 (H4), and the major fatty acids (>10 %) were iso-C16 : 0 and anteiso-C14 : 0. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and an unidentified phospholipid. On the basis of phenotypic, genotypic and phylogenetic data, strain CFH 30205T merits representation of a novel species of the genus Nocardioides , for which the name Nocardioides allogilvus sp. nov. is proposed. The type strain is CFH 30205T (=KCTC 49020T=CGMCC 4.7457T).

The core of the tumor microenvironment in the hematological system is formed by bone marrow stromal cells (BMSCs). In the present study, we explored the interaction between the urokinase plasminogen activator (uPA) system and the leukemia bone marrow microenvironment (BMM). We established BMSCs–HL60 and HS-5–K562 co-culture models in direct contact mode to simulate the BMM in leukemia. In BMSCs-HL60 co-culture model, the expression levels of uPA, uPA receptor (uPAR), plasminogen activator inhibitor 1 (PAI-1) and vascular endothelial growth factor (VEGF) in BMSCs were higher than those in mono-cultured BMSCs. Matrix metalloproteinase (MMP)-9 (MMP-9) was up-regulated in co-cultured HL60 cells. In HS-5–K562 co-culture model, only uPA, PAI-1, and VEGF-A were up-regulated in HS-5 cells. The levels of the uPA protein in the co-culture supernatant were significantly higher than that of mono-cultured BMSCs or HS-5 cells. Our findings demonstrate that the co-culture stimulates the production of uPA, uPAR, PAI-1, MMP-9, and VEGF-A by BMSCs. It could further explain how the uPA system in leukemia cells is involved in the growth, development, and prognosis of leukemia.

Treatment of multi-drug resistant (MDR) Escherichia coli intestinal infections are being hampered by the presence of the mcr-1 (colistin) and tet (tetracycline) resistance genes in these strains. We screened seven traditional Chinese medicines for their ability to synergize with tetracycline to provide an effective new drug for the treatment of animal intestinal diseases caused by MDR E. coli. Our primary screen identified quercetin as a compound that reduced the minimum inhibitory concentration (MIC) of tetracycline against the E. coli standard test strain American Type Culture Collection (ATCC) 25922 and clinical isolates fourfold from 4 and 256 μg/mL to 1 and 64 μg/mL, respectively. Low levels of quercetin in combination with tetracycline were bactericidal for clinical E. coli isolates and after 24 h, the differences between this combination and each drug singly were 108 CFU/mL. We used this combination therapy in a mouse infection model and found 100% survival after 48 h compared with

Tomato (Solanum lycopersicum) phytochemicals, which include phytoene, phytofluene, beta-carotene, flavonoids, lycopene, and polyphenols, have been shown to improve the effects of fasting on plasma triglyceride (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), total cholesterol (TC), and fasting blood sugar (FBS). The aim of this study was to systematically evaluate the effects of Tomato TC, TG, HDL, LDL, and FBS in humans. A systematic literature search was conducted in PubMed/MEDLINE, Web of sciences, and SCOPUS databases by two researchers for studies published until August of 2019 without language and time limitations. Results were combined with random effect models. Six studies were included in this meta-analysis. Combined results reveal a significant reduction in cholesterol (weighted mean difference [WMD]: -4.39 mg/dl, 95% CI: -7.09, -1.68, I2 = % 48, p heterogeneity: .05), TG (WMD: -3.94 mg/dl, 95% CI: -7.67, -0.21, I2 = % 90, p heterogeneity: .001), LDL levels (WMD: -2.09 mg/dl, 95% CI: -3.73, -0.81, I2 = % 78, p heterogeneity: .001), and increasing in HDL levels (WMD: 2.25 mg/dl, 95% CI: 0.41, 4.10, I2 = % 97, p heterogeneity: .001). Tomato was found to have a higher reduction effect on TG and LDL in younger participants. While pooled results indicate no significant effect on FBS levels (WMD: 0.59 mg/dl, 95% CI: -0.28, 1.46, I2 = % 95, p heterogeneity: .001). In conclusion, the results indicate a significant reduction in total cholesterol, TG, and LDL and increase in HDL levels that is caused by tomato consumption.

Background: Real-world evidence includes data from retrospective/prospective observational studies and observational registries, and provides insights beyond those addressed by randomized controlled trials. This study aimed to evaluate the effectiveness and safety of a clonidine adhesive patch (CAP) for children with tic disorder (TD) in a real-world setting (RWS). Methods: This was an open-label, non-interventional, post-marketing, observational study in a RWS. Children diagnosed with TDs were enrolled from a pediatric neurology clinic in China, and the change in tic symptom severity following 6 weeks pharmacologic treatments was investigated using Yale Global Tic Severity Scale (YGTSS) during visits at weeks 0, 4, 8, and 12. Results: Of 150 patients, 76% (114/150) were male (age range, 3.03-14.24 years; mean, 8.11 ± 2.48 years). Patients were divided into three groups: tiapride (n = 94), CAP (n = 14), and CAP + tiapride (n = 42). The mean YGTSS improved 11.02, 15.14, 11.13 points from baseline to posttreatment for tiapride, CAP, and CAP + tiapride, respectively, but variance analysis showed there was no significant difference in YGTSS related to different pharmacologic intervention during subsequent visits at weeks 4, 8, and 12. Repeated measure analysis showed there was no significant difference between different medication types for reducing the YGTSS score (F = 0.553, P = 0.576). No serious adverse events (AEs) occurred, and there was no significant difference in the prevalence of AEs between the three groups. Conclusion: The CAP is effective and safe for TD management in a RWS, because of the limitation of sample size and the period of follow up, observational studies with longer-term outcomes, and larger sample size are needed.

Acute myocardial infarction (AMI) is an acute heart disease. Cycloastragenol, as a natural product, inhibits inflammation and protects cardiomyocytes. Cycloastragenol (Y006) modulates inflammation in AMI is not known. To explore the function of Cycloastragenol in AMI, this study investigated the effect of Y006 and its mechanisms both in vitro and in vivo. Y006 influences the concentration of 11 proteins, as shown by a proteomics analysis, immunohistochemistry and western blotting. Among these 11 proteins, Erk1/2, PLCG1, IKBKG, and ZEB1 are related to inflammatory regulation. BAX, COX2, and GSK3β are involved in modulating cardiomyocyte apoptosis, and RhoA and DSC2 are directly associated with myocardial function. However, the functions of ARHGAP17 and Rit2 in heart are less well established. Additionally, Y006 suppressed TNF-α, IFN-γ and IL-17 production in PBMCs (peripheral blood monocytes) from patients with acute myocardial infarction and enhanced IL-10 and IL-4 expression. Similar results were obtained in a rat model of AMI by flow cytometry detection and ELISA. Our findings indicate that Y006 protects rats from AMI through direct or indirect inhibition of inflammation and cardiomyocyte apoptosis. However, the specific mechanism of Y006's protective function requires further study. Nonetheless, this research revealed a novel aspect for the treatment of myocardial infarction. SIGNIFICANCE: In the present study, we undertook the first proteomic evaluation of Cycloastragenol (Y006) function in acute myocardial infarction (AMI). Y006 significantly improved myocardial function in vivo by regulating multiple molecular expressions. Hypoxia is a direct reason for AMI. And our data support a role of Y006 in gene expression, cell apoptosis under hypoxia. The conclusions of this research assist to explain the potential molecular mechanism in Cycloastragenol treating AMI and supply a new method for ameliorating AMI.

BackgroundIn higher plants, inflorescence architecture is an important agronomic trait directly determining seed yield. However, little information is available on the regulatory mechanism of inflorescence development in perennial woody plants. Based on two inflorescence branching mutants, we investigated the transcriptome differences in inflorescence buds between two mutants and wild-type (WT) plants by RNA-Seq to identify the genes and regulatory networks controlling inflorescence architecture inJatropha curcasL., a perennial woody plant belonging to Euphorbiaceae.ResultsTwo inflorescence branching mutants were identified in germplasm collection ofJatropha.Theduo xiao hua(dxh) mutant has a seven-order branch inflorescence, and thegynoecy(g) mutant has a three-order branch inflorescence, while WTJatrophahas predominantly four-order branch inflorescence, occasionally the three- or five-order branch inflorescences in fields. Using weighted gene correlation network analysis (WGCNA), we identified several hub genes involved in the cytokinin metabolic pathway from modules highly associated with inflorescence phenotypes. Among them,Jatropha ADENOSINE KINASE 2(JcADK2),ADENINE PHOSPHORIBOSYL TRANSFERASE 1(JcAPT1),CYTOKININ OXIDASE 3(JcCKX3),ISOPENTENYLTRANSFERASE 5(JcIPT5),LONELY GUY 3(JcLOG3) andJcLOG5may participate in cytokinin metabolic pathway inJatropha. Consistently, exogenous application of cytokinin (6-benzyladenine, 6-BA) on inflorescence buds induced high-branch inflorescence phenotype in both low-branch inflorescence mutant (g) and WT plants. These results suggested that cytokinin is an important regulator in controlling inflorescence branching inJatropha. In addition, comparative transcriptome analysis showed thatArabidopsishomologous genesJatropha AGAMOUS-LIKE 6(JcAGL6),JcAGL24,FRUITFUL(JcFUL),LEAFY(JcLFY),SEPALLATAs(JcSEPs),TERMINAL FLOWER 1(JcTFL1), andWUSCHEL-RELATED HOMEOBOX 3(JcWOX3), were differentially expressed in inflorescence buds betweendxhandgmutants and WT plants, indicating that they may participate in inflorescence development inJatropha. The expression ofJcTFL1was downregulated, while the expression ofJcLFYandJcAP1were upregulated in inflorescences in low-branchgmutant.ConclusionsCytokinin is an important regulator in controlling inflorescence branching inJatropha.The regulation of inflorescence architecture by the genes involved in floral development, includingTFL1,LFYandAP1, may be conservative inJatrophaandArabidopsis. Our results provide helpful information for elucidating the regulatory mechanism of inflorescence architecture inJatropha.

The development of novel polymer carriers, which have well-defined structures and desired conjugative abiltiy to therapeutic agents, is still an urgent requirement in the field of polymer–drug conjugates (PDCs) used for stimuli-responsive drug delivery systems. Herein, we present the controlled synthesis of a novel amphiphilic polynorbornene-based block copolymer, side-chain containing hydrophobic functionalizable benzaldehyde groups and hydrophilic dentritic triethylene glycol (TEG) moieties, by the ring-opening metathesis polymerization (ROMP) using the 3rd generation Grubbs catalyst 1 as the initiator. The obtained copolymer can self-assemble into spherical micelles with the average size of 84 nm in water, and its remarkable ability as the polymer carrier to fabricate PDCs was fully confirmed by the efficient covalently Schiff-base linking of its side-chain benzaldehyde groups to amino groups of model drugs including O-benzylhydroxylamine (BHA), 1-hexadecanamine, tryptophan and benzocaine. Notably, torispherical micelles with the average size of 90 nm were also obtained by the self-assembly of the formed polymer-BHA conjugate, and the pH-triggered release of BHA molecules from the micelles was observed at acidic environments (for example, pH 4.0 and 2.5). Therefore, the present polynorbornene block copolymer is expected to find potential applications in the stimuli-responsive drug delivery systems as a promising polymer carrier to form PDCs via acid-responsive Schiff-base linkage with amino-containing drugs such as doxorubicin, daunorubicin, epirubicin and pirarubicin.

Nine new isoquinoline alkaloids, including two proaporphine (1–2), three aporphine (3–5), two oxoaporphine (6–7), and two seco-bisbenzylisoquinoline (8–9), together with three known alkaloids (10−12) were isolated from the whole plant of Thalictrum wangii. Their structures were established on the basis of spectroscopic data. The antitumor activities of the isolated compounds were evaluated in vitro against glioma stem cells. Compounds 3–8 showed the cytotoxicity with IC50 values 15–20 μg/mL.

A Gram-stain-positive, aerobic, motile with peritrichous flagella, rod-shaped bacterium, designated CFH S0170T, was isolated from a soil sample collected from Catba island in Ha Long Bay, Hai Phong City, Vietnam. Comparison of the 16S rRNA gene sequences showed that strain CFH S0170T belonged to the genus Paenibacillus and showed closest relationship with Paenibacillus vulneris CCUG 53270T (98.1 % similarity). Phylogenetic analysis demonstrated that the novel candidate formed a coherent branch with P. vulneris CCUG 53270T and Paenibacillus yunnanensis YN2T. Furthermore, the novel strain shared 87.2 % rpoB gene sequence similarity with P. vulneris CCUG 53270T. Growth of strain CFH S0170T occurred at 10–40 °C, pH 6.0–8.0 and with 0–2.0 % (w/v) NaCl. Strain CFH S0170T contained mannose, glucose and rhamnose as the major whole-cell sugars. The cell-wall peptidoglycan contained meso-diaminopimelic acid, glutamic acid, lysine and aspartic acid. The polar lipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, glycolipids and phospholipids. The dominant cellular fatty acids included anteiso-C15 : 0 and C15 : 0. The genomic DNA G+C content was 50.9 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic analysis, strain CFH S0170T is affiliated to the genus Paenibacillus , but could be distinguished from other valid species of this genus. It is concluded that strain CFH S0170T should be considered to represent a novel species of the genus Paenibacillus , for which the name Paenibacillus esterisolvens sp. nov. is proposed. The type strain is CFH S0170T (=KCTC 33624T=BCRC 80802T).

This study explores the impacts of materials, such as adsorbents and electrodes, on the energy efficiency of a 4-step ESA cycle for CO2 capture. Three types of adsorbents including activated carbon ...

The hierarchical BiOClxBr1–x was synthesized by a simple solvothermal method. The samples were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), UV-visible diffuse reflectance spectroscopy (UV-vis DRS) and Brunauer-Emmett-Teller adsorption method. Compared to pure BiOCl or BiOBr, the BiOClxBr1–x solid solution has enhanced photocatalytic degradation activity for rhodamine B. This phenomenon can be explained to the hierarchical structure, lager specific surface area and appropriate energy gap of the obtained BiOClxBr1–x solid solution. The renewability and stability of photocatalyst were determinated and a possible mechanism of photocatalytic degradation was also proposed.

A rapid, specific, and sensitive analysis for simultaneous determination of fourteen components (daidzein, fermononetin, apigenin, luteolin, puerarin, ononin, calycosin-7-O-β-D-glucoside, tanshinol, rosmarinic acid, alkanoic acid, salvianolic acid B, berberine, jatrorrhizin, and palmatine) of Yigan Jiangzhi formula (YGJZF, a clinical experienced formula for damp-heat syndrome) in rat plasma was developed and validated using ultraperformance liquid chromatography coupled with mass spectrometry. Lower limit of quantitation ranged from 0.2–10.0 ng/mL, and the calibration curves showed good linearity over 500 times of measuring range. The validated method was successfully applied to the pharmacokinetics investigation of the fourteen compounds in rat plasma after oral administration of two different doses of YGJZF. Compared with the low-dose group of YGJZF, the high-dose group showed significant increase (P<0.01 or P<0.05) in maximum plasma concentration, maximum concentration time, and area under the plasma concentration-time curve and decrease (P<0.01 or P<0.05) in clearance of most of the fourteen analytes, which suggested that the bioavailability of these components could be enhanced by increasing dosage. The above results may provide useful information for cognizing the relationship between in vitro and in vivo data of the fourteen bioactive ingredients of YGJZF and further guiding rational clinical drug prescription.

BackgroundPeritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD). The goal of this study was to investigate the anti-fibrotic effects of curcumin on the PF response to PD and its’ mechanism.MethodsMale Sprague–Dawley rats were infused with 20 mL of 4.25% glucose-based standard PD fluid for 8 consecutive weeks to establish PF model and then divided into five groups: Control, received sham operation and 0.9% physiological saline; PD, received 4.25% standard PD fluid; Curcumin, PD rats injected intraperitoeally with curcumin for 8 weeks at doses of 10, 20 or 40 mg/kg. Masson’s staining was performed to evaluate the extent of PF. Peritoneal Equilibration Test (PET) was conducted to assess ultrafiltration volume (UFV) and mass transfer of glucose (MTG), quantitative RT-PCR, and immunohistochemistry or western blotting were performed to measure the expression levels of inflammation and fibrosis-associated factors. We also detected the TGF-β1 in peritoneal fluid by ELISA.ResultsCompared with the control group, the PD rats showed decreased UFV (2.54 ± 0.48 to 9.87 ± 0.78 mL,p p p ConclusionsPresent results demonstrate that curcumin showed a protective effect on PD-related PF and suggest an implication of TAK1, p38 and JNK pathway in mediating the benefical effects of curcumin.

Preadipocyte migration is a fundamental and important process for the development of tissue organization, especially in the development of primitive adipose tissue and adipocyte tissue wound healing. However, excessive migration may result in abnormal development and fibrosis-related diseases such as hypertrophic scar. We previously reported that type I collagen (collagen I) enhanced migration of 3T3-L1 preadipocytes via phosphorylation and/or acetylation of NF-κB p65, and the enhanced cell migration is repressed by silibinin treatment through sirt1. It is known that sirt1 has an ability to deacetylate acetylated NF-κB p65, but little is known about the effect of sirt1 on phosphorylated NF-κB p65. This study aims to examine the potential effect of sirt1 on the regulation of phosphorylated NF-κB p65 and the underlying mechanism. Autophagy is involved in many physiological and pathological processes, including regulation of cell migration as well as in cellular homeostasis. The present study demonstrates that silibinin induces autophagy in a dose-dependent manner in 3T3-L1 cells. Autophagy is under the regulation of sirt1/AMPK pathway, and inhibits collagen I-enhanced migration of 3T3-L1 cells through negative regulation of NF-κB p65 phosphorylation but not acetylation. The expression of peroxisome proliferator-activated receptor α (PPARα) is up-regulated with silibinin accompanying up-regulation of autophagy through activating sirt1 in 3T3-L1 cells. Taken together, these findings indicate that silibinin-induced autophagy is mediated by up-regulation of PPARα-sirt1-AMPK, contributing to repression of type I collagen-enhanced migration in murine 3T3-L1 preadipocytes through down-regulation of phosphorylated NF-κB p65.

Lotus predominantly accumulates benzylisoquinoline alkaloids (BIAs), but their biosynthesis and regulation remain unclear. Here, we investigated structural and regulatory genes involved in BIA accumulation in lotus. Two clustered CYP80 genes were identified to be responsible for the biosynthesis of bis-BIAs and aporphine-type BIAs, respectively, and their tissue-specific expression causes divergence in alkaloid component between leaf and embryo. In contrast with the common (S)-reticuline precursor for most BIAs, aporphine alkaloids in lotus leaf may result from the (S)-N-methylcoclaurine precursor. Structural diversity of BIA alkaloids in the leaf is attributed to enzymatic modifications, including intramolecular C–C phenol coupling on ring A and methylation and demethylation at certain positions. Additionally, most BIA biosynthetic pathway genes show higher levels of expression in the leaf of high-BIA cultivar compared with low-BIA cultivar, suggesting transcriptional regulation of BIA accumulation in lotus. Five transcription factors, including three MYBs, one ethylene-responsive factor, and one basic helix–loop–helix (bHLH), were identified to be candidate regulators of BIA biosynthesis in lotus. Our study reveals a BIA biosynthetic pathway and its transcriptional regulation in lotus, which will enable a deeper understanding of BIA biosynthesis in plants., Synthesis of medicinal compounds in lotus Researchers at the Chinese Academy of Sciences have discovered the genes in lotus responsible for the synthesis of benzylisoquinole alkaloids (BIAs), a diverse set of pharmacologically significant plant metabolites. By comparing gene expression in two lotus varieties, a high- and low-BIA cultivar, they identified the genes that were active during BIA biosynthesis as well as five transcription factors which regulate the process. One of the biosynthesis genes is expressed more strongly in the embryo and another in the leaves, leading to the accumulation of different types of BIAs in these tissues. Although many of these genes are related to known BIA synthesis genes in other species, identifying the lotus equivalents not only reveals the particulars of the process in this species but also expands our understanding of BIA synthesis in general.

Fluoride calcium silicate (FCS) are widely used in dental tissue engineering due to their excellent biological properties. This study aimed to develop novel FCS with multiple biofunctions as toothpaste additives. In this study, the preparation of composite FCS, morphologies of the composites and the in vitro biofunctions were investigated. Calcium silicate with 0.7% (wt) fluoride was prepared by co-precipitation method. Pure calcium silicate (CS) was synthesized for controlling study. Biomimetic mineralization study was conducted in simulated body fluid (SBF), the composition, phase structure, apatite formation and morphology were investigated by X-ray Fluorescence Analysis (XPS), X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and transmission electron microscope (TEM). In vitro cell viability studies showed that the fluoride ions promoted cell proliferation and differentiation. This study indicated that FCS shown good bioactivity to induce apatite formation and it could be a promising toothpaste additives with specific biofunction.

Ethnopharmacological relevance Leaf of Alstonia scholaris (L.) R. Br. (Apocynaceae), a wide used ethic-medicine in many Asia and Africa counties, has also been recorded as the common traditional Chinese medicine for treatment of illnesses in respiratory system by Dai people. Aim of the study To provide experimental data of clinical adaption of total indole alkaloids (TA) from leaf of A. scholaris for treating post-infectious cough in phase II clinical trial. Materials and methods To model post-infectious cough, all animals except control group were instilled intra-tracheal with lipopolysaccharide (LPS) (80 μg/50 µL/mouse), followed by subsequent exposure to cigarette smoke (CS) for 30 min per day for a total of 30 days. Mice were orally given TA at dose of 10, 25, 50 mg/kg, and four main alkaloids (Sch: scholaricine, Epi: 19-epischolaricine, Val: vallesamine, Pic: picrinine) once daily. Cellular infiltration was assessed in the broncho-alveolar lavage fluid (BALF). Expression of interleukin-6 (IL-6) and C-reactive protein (CRP) in the serum was determined, the superoxide dismutase (SOD) activity as well as malondialdehyde (MDA) content in the serum and homogenate were examined. Finally, histopathological examination in the lungs was assessed by H. E. staining. Results After administration of TA and four major alkaloids respectively, the symptoms of cough in mice were obviously attenuated. Total white blood cells (WBC) and neutrophils (NEU) amounts in BALF were reduced obviously and the pathological damage of lung was also attenuated. There was also significant reduction in IL-6, CRP, MDA and a marked improvement in SOD. Conclusions The efficacy of indole alkaloids against post-infectious cough (PIC) was shown in the down-regulation of inflammatory cells, cytokines, and the balance of antioxidants. What's more, the pharmacological effects of TA were better than single indole alkaloid, which might be related to the synergic effect of four major alkaloids., Graphical abstract fx1

The dynamic changes of dissolved organic matter (DOM) during nitrate transport were investigated to explore the relationship between carbon sources and the nitrate reduction process in a loose-pore geothermal reservoir. Batch experiments were performed at four temperature levels (4 °C, 25 °C, 35 °C, and 45 °C) to determine the characteristics of the DOM extracted from the geothermal reservoir matrix. According to its fluorescence spectra, fluorescence index (FI), and biological/autochthonous index (BIX), the DOM was mainly derived by autochthonous microbial processes. Column experiments were carried out at 25 °C, 35 °C and 45 °C to determine the dynamic changes of the matrix DOM during nitrate transport in the simulated geothermal reservoir. The dynamic changes of the FIs; the fluorescence intensities (divided by dissolved organic carbon) of peaks B1 and T1; and concentrations of NO3−-N, NO2−-N, NH4+-N and the total dissolved inorganic nitrogen (∑N) in the column effluent within 412 h (10.5 PV) indicated that the reduction rate of nitrate and the production of denitrifiers were enhanced with an increase in temperature. Although a red shift of peak T2 during experiment at 35 and 45 °C implied the variation of the aromatic components of DOM during denitrification, low molecular weight aliphatic hydrocarbons in the matrix DOM were more active as electron donors than the aromatic compounds, as indicated by the variations of the effluent pH and SUVA254 values. No obvious trend in the variation of the BIX with temperature was observed possibly due to the short test duration of the column experiments. The findings should advance our understanding of the biological transformation of nitrate in loose-pore geothermal reservoirs.

Objective Recent studies have demonstrated that Sinomenine (SIN) exerted anti-inflammatory effect in various immune-related diseases. However, the effect of SIN on glucocorticoids dermatitis has not been investigated. In our study, we aimed to explore the effect of SIN on lipopolysaccharide (LPS)-induced inflammatory injury in HaCaT cells. Materials and methods We constructed an inflammatory injury model of LPS-induced HaCaT cells, then SIN was added to LPS-treated cells, cell viability, apoptosis, apoptosis-associated factors and inflammatory cytokines were detected by CCK-8, flow cytometry, western blot, qRT-PCR and ELISA. Subsequently, miR-101 mimic and mimic control were transfected into HaCaT cells to investigate the effect of SIN and miR-101 on LPS-induced cells injury. Furthermore, MKP-1 and JNK signal pathways were measured by qRT-PCR and western blot. Finally, the animal experiment was performed to further clarify the effect of SIN on inflammatoty injury. Results LPS suppressed cell viability, promoted apoptosis and increased IL-6, IL-8 and TNF-α expressions and secretions in HaCaT cells. SIN significantly alleviated LPS-induced HaCaT cells injury. Additionally, SIN down-regulated miR-101 expression, and the protective effect of SIN on LPS-induced inflammatory injury was abolished by miR-101 overexpression. Besides, SIN promoted MKP-1 expression by down-regulation of miR-101, and SIN inhibited JNK signal pathway by up-regulation of MKP-1 expression in LPS-treated HaCaT cells. Animal experiments revealed that SIN exhibited anti-inflammatory effects in vivo . Conclusions The data indicated that SIN attenuated LPS-induced inflammatory injury by regulation of miR-101, MKP-1 and JNK pathway. These findings might provide a novel method for treatment of glucocorticoids dermatitis.

Two 3D modular designed coordination polymers, namely, {[H2N(CH3)2]2[Mn(TPT)]}n (1), and {[Cd(TPT)0.5(bib)]·0.5H2O}n (2) (H4TPT = p-terphenyl-2,2″,5″,5‴-tetracarboxylate acid, and bib = 1,3-bis((imidazol-1-yl) benzene) have been synthesized and structural characterized by EA, IR, TG, PXRD. Single-crystal X-ray diffraction analyses reveal that complex 1 is a 3D 4-connected {42.63.8}–sra net with the tiling modular being [42.62.82] = [4a.4b.62.8a.8b] (transitivity is 2451). While complex 2 is a 3D (4,4)-connected {64.82}{66}2–bbf net with tiling modular is [6.82]+[63.8] = [6 c.8a.8b]+[6a.6b.6 c.8a] (transitivity is 2352). The variable-temperature susceptibility of 1 has been investigated. Besides, complex 2 exhibits highly sensitive sensing of FeIII ions in DMF solution.

Objective Dementia with Lewy bodies (DLB) is a common type of neurodegenerative dementia. Molecular neuroimaging using dopamine transporter (DaT), Pittsburgh compound B (PIB), and fluorodeoxyglucose (FDG) positron emission tomography (PET) has advantages in detecting dopaminergic neuron loss, abnormal amyloid β-protein deposition, and glucose metabolism changes in patients with neurodegenerative disorders. However, the multi-modality molecular imaging features of patients with DLB have rarely been reported. Methods Five patients with a probable diagnosis of DLB were enrolled. PET/magnetic resonance imaging was performed with three tracers: 11C-β-CFT, 11C-PIB, and 18F-FDG. Clinical and imaging characteristics were analyzed. Results All patients with DLB showed reduced uptake in the bilateral putamen on DaT PET, increased uptake throughout the cerebral cortex on PIB PET, and intact metabolism of the posterior cingulate gyrus on FDG PET. Conclusion Multimodal molecular imaging is helpful for early diagnosis of DLB. Studies with larger sample sizes are needed to confirm the molecular imaging differences between DLB and Alzheimer’s disease and Parkinson’s disease dementia.