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Background:. Circular RNA (circRNA) is a type of closed circular noncoding RNA (ncRNA), mostly formed by back-splicing or alternative splicing of pre-messenger RNA (mRNA). The aim of this study was to explore the expression profile of circRNA in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and discover potential molecular markers of AS. Methods:. The circRNA microarray technology was used to detect the expression of circRNAs in the peripheral blood of 6 patients with AS and 6 healthy controls (HC). To screen the differentially expressed circRNAs by fold change (FC) and P value, these differentially expressed circRNAs were analyzed by bioinformatics. In 60 cases of AS and 30 cases of HC, 4 circRNAs were subjected to real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and their correlation with various clinical indicators was analyzed. Finally, the receiver operating characteristic (ROC) curve was used to analyze their potential as AS diagnostic markers. Results:. The microarray results showed that there were 1369 significantly differently expressed (P 1.5) circRNAs between the AS and HC groups (675 upregulated and 694 downregulated). The results of bioinformatics analysis suggested that they were mainly involved in “enzyme binding,” “adenosine ribonucleotide binding,” “MAPK signaling pathway”, etc. The RT-qPCR results showed that the expressions of hsa_circRNA_001544 (U = 486.5, P

Background:. Accumulating evidence suggests that lithium influences mesenchymal stem cell (MSC) proliferation and osteogenic differentiation. As decreased bone formation in femoral heads is induced by glucocorticoids (GCs), we hypothesized that lithium has a protective effect on GC-induced osteonecrosis of femoral heads (ONFH). Methods:. A rat ONFH model was induced by methylprednisolone (MP) and the effect of lithium chloride on the models was evaluated. Micro-computed tomography (CT)-based angiography and bone scanning were performed to analyze the vessels and bone structure in the femoral heads. Hematoxylin and eosin and immunohistochemical staining were performed to evaluate the trabecular structure and osteocalcin (OCN) expression, respectively. Bone marrow-derived MSCs were isolated from the models, and their proliferative and osteogenic ability was evaluated. Western blotting and quantitative real-time polymerase chain reaction were performed to detect osteogenic-related proteins including Runx2, alkaline phosphatase, and Collagen I. Results:. Micro-CT analysis showed a high degree of osteonecrotic changes in the rats that received only MP injection. Treatment with lithium reduced this significantly in rats that received lithium (MP + Li group); while 18/20 of the femoral heads in the MP showed severe osteonecrosis, only 5/20 in the MP + Li showed mild osteonecrotic changes. The MP + Li group also displayed a higher vessel volume than the MP group (0.2193 mm3vs. 0.0811 mm3, P

A gold tube simulation device was used to study the cleavage of representative compounds into gas. The goal of this study is to investigate hydrogen isotope composition change of gaseous hydrocarbons during maturity. Gas chromatography and isotopic analyses were conducted to determine how the yield of natural gas components and their hydrogen isotopic composition were related to experimental temperature and heating rate. A chemical kinetic model for the generation of each component of the natural gas and for the hydrogen isotopic fractionation was established and calibrated based on the results. Results indicate that the hydrogen isotopic fractionation during the evolution of various gas-forming organic materials can be satisfactorily described by chemical kinetic models. During regular methane generation, the reactions at low–activation–energy region had a greater contribution than the high–activation-energy region. While the reactions with high–activation-energy region had greater contribution of deuterium-rich methane. Compared with carbon isotope fractionation, this results in a greater hydrogen isotopic fractionation, which is more sensitive to changes in maturity. This study lays a foundation for further investigations of genesis and maturity of natural gas provided by hydrogen isotopic fractionation. It also provides fundamental knowledge for investigating the filling history of natural gas reservoir and for identifying.

Coordination polymers, commonly known as infinite crystalline lattices, are versatile networks and have diverse potential applications in the fields of gas storage, molecular separation, catalysis, optics, and drug delivery, among other areas. Secondary building blocks, mainly incorporating rigid polydentate organic linkers and metal ions or clusters, are commonly employed to construct coordination polymers. Recently, novel building blocks such as coordination polyhedra have been utilized as metal nodes to fabricate coordination polymers. Benefiting from the rigid porous structure of the coordination polyhedron, prefabricated designer "pores" can be incorporated in this type of coordinate polymer. In this Account, coordination polymers built by pyrogallol[4]arene-assembled metal-organic nanocapsules are summarized. This class of metal-organic nanocapsule possesses the following advantages that make them excellent candidates in the construction of coordination polymers: (i) Various geometrical shapes with different volumes of the inner cavities can be obtained from these capsules. Among them, the two main categories illustrated are dimeric and hexameric capsules, which comprise two and six pyrogallol[4]arenes units, respectively. (ii) A wide range of possible metal ions ranging from main group metals to transition metals and even lanthanides have been demonstrated to seam the capsules. Therefore, these coordination polymers can be endowed with fascinating functionalities such as magnetism, semiconductivity, luminescence, and radioactivity. (iii) Up to 24 metal ions have been successfully embedded on the surface of the nanocapsule, each a potential reaction site in the construction of coordination polymers, opening up pathways for the formation of multidimensional frameworks.In this Account, we focus primarily on the synthesis and the structural information on pyrogallol[4]arene-derived coordination polymers. Coordination polymers can be formed by introducing linkers with two coordination sites, using pyrogallol[4]arenes with coordination sites on the tail, or even via metal ions cross-linking with each other. Machine learning was recently developed to help us predict and screen the structures of the coordination polymers. With single crystal analysis in hand, detailed structural information provides a molecular-level perspective. Significantly, following the formation of coordination polymers, the overall shape and structure of the discrete metal-organic nanocapsules remains essentially unchanged, with full retention of the prefabricated pores. If a rigid linker is used to connect capsules, more than one lattice void with different volumes can be found within the framework. Thus, molecules with different sizes could potentially be encapsulated within these coordination polymers. In addition, flexible ligands can also be employed as linkers. For example, polymers have been employed as large linkers that transform the crystalline coordination polymers into polymer matrices, paving the way toward the synthesis of advanced functional materials. Overall, coordination polymers constructed with pyrogallol[4]arene-assembled metal-organic nanocapsules show wide diversity and tunability in structure and fascinating properties, as well as the promise of built-in functionality in the future.

Excessive consumption of fructose, the sweetest of all naturally occurring carbohydrates, has been linked to worldwide epidemics of metabolic diseases in humans, and it is considered an independent risk factor for cardiovascular diseases. We provide an overview about the features of fructose metabolism, as well as potential mechanisms by which excessive fructose intake is associated with the pathogenesis of metabolic diseases both in humans and rodents. To accomplish this aim, we focus on illuminating the cellular and molecular mechanisms of fructose metabolism as well as its signaling effects on metabolic and cardiovascular homeostasis in health and disease, highlighting the role of carbohydrate-responsive element–binding protein in regulating fructose metabolism.

Background:. MicroRNAs are closely associated with the progression and outcomes of multiple human diseases, including sepsis. In this study, we examined the role of miR-23a in septic injury. Methods:. Lipopolysaccharide (LPS) was used to induce sepsis in a rat model and H9C2 and HK-2 cells. miR-23a expression was evaluated in rat myocardial and kidney tissues, as well as H9C2 and HK-2 cells. A miR-23a mimic was introduced into cells to identify the role of miR-23a in cell viability, apoptosis, and the secretion of inflammatory cytokines. Furthermore, the effect of Rho-associated kinase 1 (ROCK1), a miR-23a target, on cell damage was evaluated, and molecules involved in the underlying mechanism were identified. Results:. In the rat model, miR-23a was poorly expressed in myocardial (sham vs. sepsis 1.00 ± 0.06 vs. 0.27 ± 0.03, P

Hierarchical coordination frameworks based on a novel praseodymium(III)-seamed metal–organic nanocapsule comprising dimerized pyrogallol[4]arene units are synthesized, characterized, and studied. F...

Rationale: Sirtuins are NAD+-dependent protein deacylases known to have protective effects against age-related diseases such as diabetes, cancer, and neurodegenerative disease. SIRT2 is the only primarily cytoplasmic isoform and its overall role in glucose homeostasis remains uncertain. Methods: SIRT2-knockout (KO) rats were constructed to evaluate the role of SIRT2 in glucose homeostasis. The effect of SIRT2 on β-cell function was detected by investigating the morphology, insulin secretion, and metabolomic state of islets. The deacetylation and stabilization of GKRP in β-cells by SIRT2 were determined by western blot, adenoviral infection, and immunoprecipitation. Results: SIRT2-KO rats exhibited impaired glucose tolerance and glucose-stimulated insulin secretion (GSIS), without change in insulin sensitivity. SIRT2 deficiency or inhibition by AGK2 decreased GSIS in isolated rat islets, with lowered oxygen consumption rate. Adenovirus-mediated overexpression of SIRT2 enhanced insulin secretion from rat islets. Metabolomics analysis revealed a decrease in metabolites of glycolysis and tricarboxylic acid cycle in SIRT2-KO islets compared with control islets. Our study further demonstrated that glucokinase regulatory protein (GKRP), an endogenous inhibitor of glucokinase (GCK), was expressed in rat islets. SIRT2 overexpression deacetylated GKRP in INS-1 β-cells. SIRT2 knockout or inhibition elevated GKRP protein stability in islet β-cells, leading to an increase in the interaction of GKRP and GCK. On the contrary, SIRT2 inhibition promoted the protein degradation of ALDOA, a glycolytic enzyme. Conclusions: SIRT2 ablation inhibits GSIS through blocking GKRP protein degradation and promoting ALDOA protein degradation, resulting in a decrease in glycolytic flux.

Background:. Breast cancer (BC) is a common malignancy with highly female incidence. So far the function of notoginsenoside R1 (NGR1), the extract from Panax notoginseng, has not been clearly elucidated in BC. Methods:. Optimal culture concentration and time of NGR1 were investigated by cell counting kit-8 assay. Cell proliferation ability was measured by colony formation assays. Transwell assay was used to detect the effect of NGR1 on cell migration and invasion. The apoptosis rate of cells between each group was measured by TUNEL assay. Results:. NGR1 treatment has an inhibitory effect on proliferation, migration, invasion, and angiogenesis and a stimulating effect on cell cycle arrest and apoptosis of Michigan Cancer Foundation-7 (MCF-7) cells. The 50% growth inhibitory concentration for MCF-7 cells at 24 h was 148.9 mmol/L. The proportions of MCF-7 cells arrested in the G0/G1 phase were 36.94±6.78%, 45.06±5.60%, and 59.46±5.60% in the control group, 75, and 150 mmol/L groups, respectively. Furthermore, we revealed that NGR1 treatment attenuates BC progression by targeted downregulating CCND2 and YBX3 genes. Additionally, YBX3 activates phosphatidylinositol 3-phosphate kinase (PI3K)/protein kinase B (Akt) signaling pathway by activating kirsten rat sarcoma viral oncogene, which is an activator of the PI3K/Akt signaling pathway. Conclusion:. These results suggest that NGR1 can act as an efficacious drug candidate that targets the YBX3/PI3K/Akt axis in patients with BC.

Background Ginsenoside CK (GCK) serves as the potential anti-colorectal cancer (CRC) protopanaxadiol (PPD)-type saponin, which could be mainly bio-converted to yield PPD by gut microbiota. Meanwhile, the anti-CRC effects of GCK could be altered by gut microbiota due to their different diversity in CRC patients. We aimed to investigate the bioconversion variation of GCK mediated by gut microbiota from CRC patients by comparing with healthy subjects. Methods Gut microbiota profiled by 16S rRNA gene sequencing were collected from healthy volunteers and CRC patients. GCK was incubated with gut microbiota in vitro. A LC-MS/MS method was validated to quantify GCK and PPD after incubation at different time points. Results The bioconversion of GCK in healthy subjects group was much faster than CRC group, as well as the yield of PPD. Moreover, significant differences of PPD concentration between healthy subjects group and CRC group could be observed at 12 h, 48 h and 72 h check points. According to 16S rRNA sequencing, the profiles of gut microbiota derived from healthy volunteers and CRC patients significantly varied, in which 12 differentially abundant taxon were found, such as Bifidobacterium, Roseburia, Bacteroides and Collinsella. Spearman’s correlation analysis showed bacteria enriched in healthy subjects group were positively associated with the biotransformation of GCK, while bacteria enriched in CRC group displayed non correlation character. Among them, Roseburia which could secrete β-glycosidase showed the strongest positive association with the bioconversion of GCK. Conclusions The bioconversion of GCK in healthy subjects was much faster than CRC patients mediated by gut microbiota, which might alter the anti-CRC effects of GCK.

Supramolecular tessellation is a newly emerging and promising area in supramolecular chemistry because of its unique structural aesthetics and potential applications. Herein, we investigate the "exo-wall" interactions of pillar[n]arenes and prepare fantastic hexagonal supramolecular tessellations based on perethylated pillar[6]arenes (EtP6) with electron-deficient molecules 1,5-difluoro-2,4-dinitrobenzene (DFN) and tetrafluoro-1,4-benzoquinone (TFB). The crystal structures clearly confirm that EtP6 can form highly ordered hexagonal 2D tiling patterns with DFN/TFB as linkers through cocrystallization. Moreover, the self-assembled packing arrangements in the ultimate cocrystal superstructures can be adjusted under different crystallization conditions. This work not only explores the rare exo-wall interactions based on pillar[n]arenes but also reports the fabrication of supramolecular tessellations based on pillararenes for the first time, showing a new perspective in supramolecular chemistry.

Stimuli-responsive unimolecular chirality switching is a highly intriguing topic because the molecular structure as well as its function can be adjusted simultaneously by a switching process. Herein, a novel acid/base-tunable unimolecular chirality switching system based on a pillar[5]azacrown pseudo[1]catenane is reported. The bicyclic pillar[5]azacrown pseudo[1]catenane PN4 is synthesized through fusing an azacrown ring onto one repeating unit of a pillar[5]arene. Protonation and deprotonation can reversibly regulate the conformational transformations of PN4 between self-inclusion and self-exclusion structures, which results in the chiroptical inversions of the pseudo[1]catenane. NMR spectra, circular dichroism spectra, and single-crystal structures demonstrate these processes. This pseudo[1]catenane is a novel pillararene-based unimolecular chirality switching system driven by acid/base responsiveness and reveals a new perspective on the supramolecular chirality chemistry of macrocycles.

Mitochondrial injury and endoplasmic reticulum (ER) stress are considered to be the key mechanisms of renal ischemia-reperfusion (I/R) injury. Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER, known as mitochondrial-associated membranes. The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes, which can play an important role in mitochondrial damage, ER stress, lipid homeostasis, and cell death. Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury. A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets. In this review, we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms, such as mitophagy, mitochondrial fission, mitochondrial fusion, apoptosis and necrosis, ER stress, mitochondrial substance transport, and lipid metabolism.

Psoriasis is considered a systemic disease associated with metabolic abnormalities, and it is important to understand the mechanisms by which metabolism affects pathophysiological processes both holistically and systematically. Metabolites are closely related to disease phenotypes, especially in systemic diseases under multifactorial modulation. The emergence of metabolomics has provided information regarding metabolite changes in lesions and circulation and deepened our understanding of the association between metabolic reprogramming and psoriasis. Metabolomics has great potential for the development of effective biomarkers for clinical diagnosis, therapeutic monitoring, prediction of the efficacy of psoriasis management, and further discovery of new metabolism-based therapeutic targets.

Herein we develop a new pillar[5]arene-mediated supramolecular polymerization strategy to control the assembly of dyes 4,7-di-2-thienyl-2,1,3-benzothiadiazole and 4,7-di-2-thienyl-2,1,3-benzoselenadiazole in the solid state. The resulting supramolecular polymeric structures drive the dye aggregates in the solid state from parallel alignments to highly ordered "head-to-tail" structures, which effectively suppresses excimer formation and thus aggregation-caused quenching effects and enhances the solid-state emission efficiency by almost 1 order of magnitude. This, together with two-photon excited emission, endows these solid-state polymers with exciting potential in optoelectronic, photonic, and bioimaging applications.

Background. Hyperthermia in combination with DnaJA4-knockout (KO) obviously affects the anti-viral immunity of HaCaT cells. The mechanisms of this process are not yet fully explored. However, it is known that DnaJA4 interacts with actin cytoskeleton after hyperthermia. Our aim was to investigate the effects of DnaJA4 on F-actin in HaCaT cells following hyperthermia. Methods. Wild-type (WT) and DnaJA4-KO HaCaT cells were isolated at either 37°C (unheated) or 44°C (hyperthermia) for 30 min followed by testing under conditions of 37°C and assessing at 6, 12, and 24 h after hyperthermia. The cytoskeleton was observed with immunofluorescence. Flow cytometry and Western blotting were used to detect the expression of F-actin and relevant pathway protein. Results. DnaJA4-KO and hyperthermia changed the cytoskeleton morphology of HaCaT cells. F-actin expression levels were elevated in DnaJA4-KO cells compared with WT cells (6364.33 ± 989.10 vs. 4272.67 ± 918.50, P

Background. The association between free triiodothyronine (FT3) and long-term prognosis in dilated cardiomyopathy (DCM) patients has not been evaluated. The purpose of this study was to determine whether the level of FT3 could provide prognostic value in patients with DCM. Methods. Data of consecutive patients diagnosed with DCM were collected from October 2009 to December 2014. FT3 was measured by fluoroimmunoassay. Other biochemical markers, such as free thyroxin (FT4), thyroid-stimulating hormone, red blood cell, hemoglobin, blood urea nitrogen, and serum creatinine, were tested at the same time. Follow-up was performed every 3 months. The primary endpoint was all-cause mortality. Pearson analysis was used to evaluate the correlation of FT3 and other lab metrics with DCM patients’ prognosis. The association of long-term mortality in DCM and FT3 was compared using Cox hazards model. Results. Data of 176 patients diagnosed with DCM were collected. Of them, 24 patients missed FT3 values and six patients were lost to follow-up. Altogether, data of 146 patients were analyzed. During the median follow-up time of 79.9 (53.5–159.6) months, nine patients lost, 61 patients died (non-survival group), and 85 patients survived (survival group). FT3 was significantly lower in non-survival group than that in survival group (3.65 ± 0.83 pmol/L vs. 4.36 ± 1.91 pmol/L; P = 0.003). FT3 also showed a significantly positive correlation with red blood cell and hemoglobin, negatively correlated with age, blood urea nitrogen and serum creatinine (P

A strain of silicon-activating bacteria was isolated from electrolytic manganese residue (EMR); identified as a species of Ochrobactrum by integrated microscopic morphological characteristics, biochemical index determination, and clone analysis (i.e., results of 16S rRNA sequence); and temporarily named as Ochrobactrum sp. T-07 (T-07). The optimal growth conditions of the strain T-07 were obtained as follows: temperature of 30 °C, initial pH of 7.0, shaking speed of 180 rev. min−1, and loading volume of 100 mL. In order to enhance its activation activity of silicon, T-07 went through the ultraviolet (UV) mutagenesis and nitrosoguanidine (NTG) mutagenesis breeding, and the mutant strain T-07-B with higher activity was obtained. Under the optimal fermentation condition (leaching time of 20 days, temperature of 30 °C, initial pH of 7, pulp concentration of 5%, shaking speed of 180 rev. min−1, and particle diameter of EMR ≤ 180 μm), the available silicon content in the supernatant reached 98.8 mg L−1, which was 2.4 times of the original strain T-07. Therefore, T-07 can be used as a good backup in developing biological silicon fertilizer for plants.

Gut microbiota dysbiosis is a risk factor for colorectal cancer (CRC) in inflammatory bowel disease (IBD). In this study, the effects of Panax notoginseng saponins (PNS) on colitis-associated CRC progression were evaluated on an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. In vivo, PNS significantly relieved AOM/DSS-induced colon tumorigenesis and development by reducing the disease activity index (DAI) scores and colon tumor load. The 16S rRNA data of fecal samples showed that the microbiome community was obviously destructed, while PNS could recover the richness and diversity of gut microbiota. Especially, PNS could increase the abundance of Akkermansia spp. which was significantly decreased in model group and negatively correlated with the progression of CRC. Moreover, ginsenoside compound K (GC-K) was evaluated on the effects of human CRC cells, which was the main bio-transformed metabolite of PNS by gut microbiota. Our data showed that PNS played important role in the prevention of the progression of CRC, due to their regulation on the microbiome balance and microbial bio-converted product with anti-CRC activity.

Toosendanin (TSN) is a tetracyclic triterpenoid extracted from Melia toosendan Sieb, et Zucc, which primarily grows in specific areas of China. Although toosendanin (TSN) exerts antitumoral effects on various human cancer cells, its influence on gastric cancer (GC) is remains to be elucidated. MicroRNAs (miRNAs/miRs) serve crucial roles in apoptosis and proliferation of cancer cells. miR-23a-3p has been shown to be associated with human GC; however, the specific function of miR-23a-3p in GC remains unclear. Therefore, the present study aimed to elucidate the role of miR-23a-3p in the regulation of GC cell proliferation and apoptosis induced in vitro by TSN treatment. Subsequently, apoptosis-related genes expression levels were quantified by reverse transcription-quantitative PCR and western blot analysis, respectively, and the target relationship between miR-23a-3p and BCL2 was determined by luciferase reporter gene analysis. Additionally, cell proliferation and apoptosis experiments were carried out. The results indicated that TSN inhibited proliferation and induced apoptosis in MKN-45 cells. Moreover, it upregulated the expression of miR-23a-3p. B-cell lymphoma-2 (BCL2) was identified as a potential target gene of miR-23a-3p, which was demonstrated to bind to the 3′-untranslated region of BCL2 mRNA, as detected by the luciferase reporter assay. Further studies revealed that BCL2 expression was downregulated following overexpression of miR-23a-3p. In addition, the overexpression of the miR-23a-3p inhibited proliferation, induced G1 arrest and increased apoptosis in MKN-45 cells. The results of the present study demonstrated that miR-23a-3p inhibited proliferation and induced apoptosis of GC cells, which may be attributable to its direct targeting of BCL2. These results may provide a novel insight into the apoptosis of GC cells, and may lead to investigations into the mechanisms of the effects of TSN.

Periodontitis is one of the most prevalent epidemics affecting human health and life recently, and exploration of the pathogenesis and treatment of periodontitis has been valued by scholars. In recent years, sclerostin, a new factor on bone resorption and reconstruction caused by inflammation and mechanical stimulation, has been a research hotspot. This article summarizes the researches on sclerostin in periodontitis development in recent years. Among them, sclerostin has been shown to be a critical negative regulator of bone formation, thereby inhibiting bone remodeling in periodontitis development, and is closely associated with tooth movement. Besides, evidence indicates that the removal of sclerostin seems to reasonably protect the alveolar bone from resorption. Regulation of sclerostin expression is a novel, promising treatment for periodontitis and addresses several complications seen with traditional therapies; accordingly, many drugs with similar mechanisms have emerged. Moreover, the application prospect of sclerostin in periodontal therapy combined with orthodontic treatment is another promising approach. There are also a lot of drugs that regulate sclerostin. Anti-sclerostin antibody (Scl-Ab) is the most direct one that inhibits bone resorption caused by sclerostin. At present, drugs that inhibit the expression of sclerostin have been applied to the treatment of diseases such as multiple myeloma and osteoporosis. Therefore, the application of sclerostin in the oral field is just around the corner, which provides a new therapeutic bone regulation strategy in oral and general health.

Panax notoginseng saponins (PNSs) are the major health-beneficial components of P. notoginseng with very low oral bioavailability, which could be biotransformed by gut microbiota in vitro. However, in vivo biotransformation of PNS mediated by gut microbiota is not well known. This study aimed to characterize the in vivo metabolic profiles of PNS mediated by gut microbiota. The saponins and yielded metabolites in rat feces were identified and relatively quantified by ultra-performance liquid chromatography tandem/quadrupole time-of-flight mass spectrometry. Seventy-three PNS metabolites had been identified in the normal control group, but only 11 PNS metabolites were determined in the pseudo germ-free (GF) group. In addition, the main biotransformation pathway of PNS metabolism was hydrolytic and dehydration reactions. The results indicated that a significant metabolic difference was observed between the normal control group and pseudo GF group, while gut microbiota played a profound role in the biotransformation of PNS in vivo.

Tannic acid (TA) is a polyphenol compound present in wines and many beverages. Although previous works have shown that TA could cause vasodilation in an endothelial cell (EC)-dependent manner, there is hitherto no report showing whether TA could raise EC cytosolic Ca2+ concentration. In this work we examined the effects of TA on cytosolic Ca2+ of mouse brain bEND.3 EC. TA (1–30 μM) caused a slow elevation in cytosolic Ca2+ level in a concentration-dependent manner. At 30 μM, TA triggered Ca2+ influx without causing intracellular Ca2+ release. TA-triggered Ca2+ influx was suppressed by Ni2+ (a non-specific Ca2+ channel blocker), ruthenium red and SKF 96365 (non-specific TRP channel blockers), CBA (a selective TRPM4 inhibitor) and M 084 (a selective TRPC4/C5 blocker). However, TA-triggered Ca2+ influx pathway was not permeable to Mn2+. Our results suggest TA activated TRP channels, possibly TRPM4 and TRPC4/C5, to promote influx of Ca2+.

In this study, a crack-free PDMS–SiO2–BiPO4 (P/Si/Bi) composite was prepared via a solgel-assisted route by dispersing pre-prepared bismuth oxybromide into a solution that was composed of hydroxyl-terminated polydimethylsiloxane (PDMS–OH), tetraethyl orthosilicate and phosphoric acid. Analysis via the FTIR, XRD, XPS and SEM–EDX techniques demonstrated that the nonisolated BiPO4 particles with a monoclinic crystal phase were uniformly distributed on the surface of the P/Si/Bi composite, which can provide more active sites and a larger surface area for photocatalysis compared with other materials. The photocatalytic activity of the P/Si/Bi composite loaded with various mass ratios of BiPO4 (9 wt%, 12 wt%, 18 wt% and 27 wt%) was investigated via the degradation of methylene blue (MB, 10 mg/L) under UV light irradiation. It was found that the P/Si/Bi composite loaded with 18 wt% BiPO4 realized the highest degradation efficiency of MB, and its corresponding apparent rate constant was approximately 2.2 times that of the PDMS–SiO2–TiO2 composite (loaded with 18 wt% TiO2). The effects of inorganic ions on the degradation of MB were also investigated. The static contact angle and photocatalytic activity of the P/Si/Bi composite changed minimally after five cyclic experiments, thereby demonstrating its remarkable durability in sustainable applications. In addition, the photogenerated reactive species that were responsible for the degradation of MB within the P/Si/Bi composite were identified, and a photocatalytic mechanism was proposed.

Polymeric metal-organic nanocapsule networks (polyMONCs), where metal-organic nanocapsules (MONCs) are connected by functional polymers, could possess the properties of traditional polymers and also retain the structures of MONCs. In this work, we constructed novel polyMONCs based on Mg-seamed pyrogallol[4]arene-containing MONCs through supramolecular coordination-driven self-assembly. The MONCs can be successfully polymerized using poly(ethylene glycol) as the linker, and the prepared polyMONCs can be further made into gels with self-healing properties and stimuli responsiveness. Advantageously, single crystals of MONCs cross-linked by ethylene glycol/diethylene glycol were obtained, giving us direct perspectives to mimic and investigate the self-assembly process of polyMONCs.

Background: Fibroblast-like synoviocytes (FLSs), resident mesenchymal cells of synovial joints, play an important role in the pathogenesis of rheumatoid arthritis (RA). Dickkopf-1 (DKK-1) has been proposed to be a master regulator of bone remodeling in inflammatory arthritis. Here, potential impairation on the activity of FLSs derived from RA to small interfering RNAs (siRNAs) targeting DKK-1 was investigated. Methods: siRNAs targeting DKK-1 were transfected into FLSs of patients with RA. Interleukin (IL)-1β, IL-6, IL-8, matrix metalloproteinase (MMP) 2, MMP3, MMP9, transforming growth factor (TGF)-β1, TGF-β2 and monocyte chemoattractant protein (MCP)-1 levels in the cell culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Invasion assay and 3H incorporation assay were utilized to investigate the effects of siRNAs targeting DKK-1 on FLSs invasion and cell proliferation, respectively. Western blotting was performed to analyze the expression of nuclear factor (NF)-κB, interleukin-1 receptor-associated kinase (IRAK)1, extracellular regulated protein kinases (ERK)1, Jun N-terminal kinase (JNK) and β-catenin in FLSs. Results: DKK-1 targeting siRNAs inhibited the expression of DKK-1 in FLSs (P < 0.01). siRNAs induced a significant reduction of the levels of IL-6, IL-8, MMP2, MMP3 and MMP9 in FLSs compared to the control group (P < 0.05). DKK-1 targeting siRNAs inhibited the proliferation and invasion of FLSs (P < 0.05). Important molecules of pro-inflammatory signaling in FLSs, including IRAK1 and ERK1, were decreased by the inhibition of DKK-1 in FLSs. In contrast, β-catenin, a pivotal downstream molecule of the Wnt signaling pathway was increased. Conclusions: By inhibiting DKK-1, we were able to inhibit the proliferation, invasion and pro-inflammatory cytokine secretion of FLSs derived from RA, which was mediated by the ERK or the IRAK-1 signaling pathway. These data indicate the application of DKK-1 silencing could be a potential therapeutic approach to RA. Key words: Dickkopf-1; Fibroblast-like synoviocytes; Rheumatoid arthritis; small interfering RNAs

Background: Proliferative diabetic retinopathy (PDR) is a progressive stage of diabetic retinopathy featured by the formation of neovascular and proliferative membrane. Vascular endothelial growth factor (VEGF) acts as a pivot factor in the development of neovascularization. This study was to investigate the changes of intravitreal VEGF concentrations of severe PDR after intravitreal injection of conbercept (IVC) and its potential advantages to the following vitrectomy. Methods: This was a prospective, interventional, randomized controlled study. Sixty eyes (60 patients) with severe PDR and 20 eyes from 20 patients with rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy were enrolled in this study. PDR eyes were randomly assigned to three groups by sortation randomization method with 20 eyes in each based on the interval of preoperative IVC (group A: 7 days, group B: 14 days, group C: non-IVC). Another 20 eyes without diabetes were enrolled as the non-diabetic control group (group D), receiving PPV directly. Vitreous specimens of all 80 patients were collected and evaluated afterwards. The intravitreal VEGF concentration of the four groups, and the total surgical time and the intraoperative bleeding rate of the PDR groups were recorded. Results: The mean intravitreal VEGF concentrations of groups A-D were 66.6 ± 43.3, 93.1 ± 52.3, 161.4 ± 106.1 and 1.8 ± 1.2 pg/mL, respectively. It increased significantly in PDR patients (groups A, B and C) (P = 0.002

Background: Mesenchymal stem or stromal cells (MSCs) derived from the induced pluripotent stem cells (iPSCs) have uniform biological activity, which makes the clinical application of MSCs in bone repair possible. Culturing the iPSC-MSCs onto osteoconductive materials is a promising tissue engineering-based strategy in bone regeneration. The aim of this work was to evaluate the effects of semaphorin 3A (Sema3A) and hypoxia inducible factor 1 subunit alpha (HIF1α) co-overexpression on the survival and osteogenic differentiation of iPSC-MSCs. Methods: Sema3A and HIF1α were linked together with the three (GGGGS; G, glycine; S, serine) peptide fragment, and their co-expression in iPSC-MSCs was mediated by a lentiviral vector. The fusion protein retained the immune reactivity for both Sema3A and HIF1α as determined with Western blotting. iPSC-MSCs were infected with overexpression lentivirus (oeLenti) as negative control, oeLenti-Sema3A, oeLenti-HIF1α or oeLenti-Sema3A-HIF1α lentiviruses. Results: Sema3A overexpression alone promoted the osteogenic differentiation of iPSC-MSCs (the activity and/or expression of osteoblast markers, such as alkaline phosphatase, osteopontin, and osteocalcin, were upregulated), and suppressed cell survival. The Sema3A-HIF1α fusion protein showed a comparable osteoconductive effect to that of Sema3A without reducing cell survival. We further seeded iPSC-MSCs modified by SemaA-HIF1α overexpression onto hydroxyapatite (HA) scaffolds, and evaluated their growth and differentiation on this three-dimensional material. Additional data indicated that, as compared to iPSC-MSCs cultured in ordinary two-dimensional dishes, cells cultured in HA scaffolds grew (blank vs. HA scaffolds: 0.83 vs. 1.39 for survival) and differentiated better (blank vs. HA scaffolds: 11.29 vs. 16.62 for alkaline phosphatase activity). Conclusion: Modifying iPSC-MSCs with pro-osteogenic (Sema3A) and pro-survival (HIF1α) factors may represent a promising strategy to optimize tissue engineering-based strategy in bone repair. Key words: Semaphorin 3A; Hypoxia inducible factor 1 subunit alpha; Induced pluripotent stem cells; Mesenchymal stems; Cell survival; Osteogenic differentiation; Hydroxyapatite scaffolds

In this study, a core–shell catalyst based on Fe5C2@ZSM-5 (ZSM-5 capped Fe5C2 as active phase) is prepared by the coating-carbonization method for Fischer–Tropsch synthesis (FTS). Further, the designed ZSM-5 zeolites are utilized to screen the low carbon hydrocarbons from the products generated on the iron carbide active centre, and for catalytic disassembly of the long-chain hydrocarbons into low carbon olefins. Prior to utilization, the physical–chemical properties of the prepared catalysts are systematically characterized by various techniques of X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET), Fourier transform infrared (FT-IR), and scanning electron microscopy (SEM) as well as transmission electron microscopy (TEM) observations, in addition to the effects of coating-carbonization, molecular sieve coating amount, and K-doping on core–shell iron-based catalysts. Next, the performance of Fischer–Tropsch synthesis is investigated in a micro-fixed bed reactor. The results manifest that, comparing with Fe5C2 and a supported Fe/ZSM-5 catalyst prepared by the traditional impregnation method, the core–shell Fe5C2@ZSM-5 catalysts show higher CO conversion rate, reaction activity and selectivity to low-carbon olefins. Comparatively, the Fe5C2@ZSM-5C catalyst prepared by carbonization after the coating method exhibited more surface area, smaller average pore size, and more reactive active sites, resulting in the improvement of screening of high carbon hydrocarbons and the enhancement of selectivity to low carbon olefins, in comparison to those prepared by the carbonization-coating method. In conclusion, the K-doping catalyst had significantly improved the reactive activity of the core–shell Fe5C2@ZSM-5 catalyst and the selectivity to low carbon olefins, while the CO conversion on K–Fe5C2@ZSM-20C still remained good.

Supramolecular chaperones play an important role in directing the assembly of multiple protein subunits and redox-active metal ions into precise, complex and functional quaternary structures. Here we report that hydroxyl tailed C-alkylpyrogallol[4]arene ligands and redox-active MnII ions, with the assistance of proline chaperone molecules, can assemble into two-dimensional (2D) and/or three-dimensional (3D) networked nanocapsules. Dimensionality is controlled by coordination between the exterior of nanocapsule subunits, and endohedral functionalization within the 2D system is achieved via chaperone guest encapsulation. The tailoring of surface properties of nanocapsules via coordination chemistry is also shown as an effective method for the fine-tuning magnetic properties, and electrochemical and spectroscopic studies support that the nanocapsule is an effective homogeneous water-oxidation electrocatalyst, operating at pH 6.07 with an exceptionally low overpotential of 368 mV.

The lack of high-performance anode materials has become a major obstacle to the development of Li- and Na-ion batteries. Recently, 2D transition metal borides (e.g. MBenes) have attracted much attention due to their excellent stability and electrical conductivity. Unfortunately, most of the reported MBene phases typically have an intrinsic metal-rich structure with metal atoms exposed on the surface, which harmfully affect the adsorption of Li/Na atoms. Here, through crystal structure prediction combined with the first-principles density functional theory, a novel TiB3 MBene has been determined by altering the proportion of non-metallic element boron to wrap metal atoms and weaken nearest-neighbor electrostatic repulsion. Electrostatic potential analysis visually shows a surface with low potential on the TiB3 monolayer implying high adsorption capacity, and also can be used to quickly screen out the Li/Na adsorption sites. Accurate half-cell battery simulation confirmably shows that the TiB3 monolayer possesses a theoretical specific capacity of 1335.04 and 667.52 mA h g-1 for Li and Na, respectively. The TiB3 monolayer can remain metallic after adsorbing Li/Na atoms, which ensures good conductivity during battery cycling. The ultra-low barrier energy (only 38 meV for Li) and suitable open-circuit voltage indicate excellent charging and discharging capabilities. These results suggest that the TiB3 monolayer could be a promising anode material for Li- and Na-ion batteries, and provide a simple design principle for exposing non-metallic atoms on the surface.

Serious cyanobacterial blooms lead to the release of harmful microcystin-LR and ammonia to eutrophic waters, thereby posing serious challenges to zooplankton. The physiological and ecological responses of Brachionus calyciflorus Pallas to microcystin-LR and ammonia stresses were evaluated. Neonates ( 0.05). Microcystis metabolites negatively affected growth and reproductive performance of B. calyciflorus. In addition, the life-cycle parameters were related to the effects of microcystin-LR and ammonia on the GSH-related antioxidant defense system of rotifers.

Topological state of matter and high-performance electrode materials have attracted considerable attention all over the world. Here we combine these two by exploring the possibility of using In–O c...

PurposeTo retrospectively and comparatively evaluate the improvement of the efficacy and safety on the addition of 252Cf neutron intracavitary brachytherapy (ICBT), individualized or individualized with intrarectal peritumoral injection of amifostine (IPIA) to external-beam radiotherapy (EBRT) or concurrent chemo-EBRT in 314 patients with T2N0-1 or T3N0-1 low-lying rectal adenocarcinoma.MethodsPhase I: from 2009 to 2011, 157 patients were treated with additional 252Cf neutron ICBT for four fixed fractions with a total dose of 40–45 Gy-eq during the EBRT. Phase II: from 2011 to 2013, 75 patients were treated with individualized neutron ICBT delivered for two to five fractions with a total dose of 26–45 Gy-eq according to the response of tumor after concurrent chemo-EBRT. Phase III: from 2013 to 2014, 82 patients were treated with individualized ICBT protected by pretreatment IPIA.ResultsThe 4-year local control rates for the entire T2 and T3 patients were 69.4, 72.0, and 79.3%, while the 4-year overall survival rates were 63.1, 54.7, and 72.0% (P=0.08), and the 4-year disease-free survival rates were 55.4, 52.0, and 69.5% (P=0.053) in Phases I, II, and III, respectively. The late complication (LAC, ≥G2) rates were 33.8, 26.7, and 15.9%, respectively (P=0.012), and the serious LAC (≥G3) rates were 4.5, 4.2, and 0%, respectively, in Phases I, II, and III.ConclusionConcurrent chemo-EBRT combined with individualized 252Cf neutron ICBT protected by IPIA shows promising efficacy and safety in treating low-lying T2 and T3 rectal adenocarcinoma patients without surgery opportunity or willing.

The penetration process has attracted increasing attention due to its engineering and scientific value. In this work, we investigate the deformation and damage mechanism about the nanoscale penetration of single-crystal aluminum nanorod with atomistic simulations, where distinct draw ratio (∅) and different incident velocities (up) are considered. The micro deformation processes of no penetration state (within 2 km/s) and complete penetration (above 3 km/s) are both revealed. The high-speed bullet can cause high pressure and temperature at the impacted region, promoting the localized plastic deformation and even solid-liquid phase transformation. It is found that the normalized velocity of nanorod reduces approximately exponentially during penetration (up < 3 km/s), but its residual velocity linearly increased with initial incident velocity. Moreover, the impact crater is also calculated and the corresponding radius is manifested in the linear increase trend with up while inversely proportional to the ∅. Interestingly, the uniform fragmentation is observed instead of the intact spallation, attributed to the relatively thin thickness of the target. It is additionally demonstrated that the number of fragments increases with increasing up and its size distribution shows power law damping nearly. Our findings are expected to provide the atomic insight into the micro penetration phenomena and be helpful to further understand hypervelocity impact related domains.

Diabetic osteoporosis (DOP) belongs to secondary osteoporosis caused by diabetes; it has the characteristics of high morbidity and high disability. In the present study, we constructed a type 1 diabetic rat model and administered chondroitin sulfate (200 mg/kg) for 10 weeks to observe the preventive effect of chondroitin sulfate on the bone loss of diabetic rats. The results showed that chondroitin sulfate can reduce blood glucose and relieve symptoms of diabetic rats; in addition, it can significantly increase the bone mineral density, improve bone microstructure, and reduce bone marrow adipocyte number in diabetic rats; after 10 weeks of chondroitin sulfate administration, the SOD activity level was upregulated, as well as CAT levels, indicating that chondroitin sulfate can alleviate oxidative stress in diabetic rats. Chondroitin sulfate was also found to reduce the level of serum inflammatory cytokines (TNF-α, IL-1, IL-6, and MCP-1) and alleviate the inflammation in diabetic rats; bone metabolism marker detection results showed that chondroitin sulfate can reduce bone turnover in diabetic rats (decreased RANKL, CTX-1, ALP, and TRACP 5b levels were observed after 10 weeks of chondroitin sulfate administration). At the same time, the bone OPG and RUNX 2 expression levels were higher after chondroitin sulfate treatment, the bone RANKL expression was lowered, and the OPG/RANKL ratio was upregulated. All of the above indicated that chondroitin sulfate could prevent STZ-induced DOP and repair bone microstructure; the main mechanism was through anti-oxidation, anti-inflammatory, and regulating bone metabolism. Chondroitin sulfate could be used to develop anti-DOP functional foods and diet interventions for diabetes.

Background Panax notoginseng saponins (PNS) as the main effective substances from P. notoginseng with low bioavailability could be bio-converted by human gut microbiota. In our previous study, PNS metabolic variations mediated by gut microbiota have been observed between high fat, high protein (HF-HP) and low fat, plant fiber-rich (LF-PF) dietary subjects. In this study, we aimed to correspondingly characterize the relationship between distinct gut microbial species and PNS metabolites. Methods Gut microbiota were collected from HF-HP and LF-PF dietary healthy adults and profiled by 16S rRNA gene sequencing. PNS were incubated with gut microbiota in vitro. A LC–MS/MS method was developed to quantify the five main metabolites yields including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GC-K), protopanaxatriol (PPT) and protopanaxadiol (PPD). The selected microbial species, Bifidobacterium adolescentis and Lactobacillus rhamnosus, were employed to metabolize PNS for the corresponding metabolites. Results The five main metabolites were significantly different between the two diet groups. Compared with HF-HP group, the microbial genus Blautia, Bifidobacterium, Clostridium, Corynebacterium, Dorea, Enhydrobacter, Lactobacillus, Roseburia, Ruminococcus, SMB53, Streptococcus, Treponema and Weissella were enriched in LF-PF group, while Phascolarctobacterium and Oscillospira were relatively decreased. Furthermore, Spearman’s correlative analysis revealed gut microbials enriched in LF-PF and HF-HP groups were positively and negatively associated with the five metabolites, respectively. Conclusions Our data showed gut microbiota diversity led to the personalized bioconversion of PNS. Graphic Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s13020-021-00476-5., Highlights Panax notoginseng saponins could be biotransformed to generate five main metabolites, including GF1, GRh2, GC-K, PPT and PPD, by human gut microbiota. Gut microbiota profiles were significantly different in high protein, high fat and low fat, plant fiber-rich diet-pattern groups. Correlation analysis revealed potential relationships between metabolites and gut microbial species. Bifidobacterium adolescentis and Lactobacillus rhamnosus were selected as a representative species to metabolize PNS for the concerned metabolites. Supplementary Information The online version contains supplementary material available at 10.1186/s13020-021-00476-5.

Background: Gestational diabetes mellitus (GDM) is a common complication during pregnancy. Obesity and overweight are closely related to metabolic diseases and diabetes. However, the role of adipose tissue in the pathogenesis of GDM remains to be studied. The aim of this study was to investigate the correlation of vitamin D (VD) levels, VD receptor (VDR), and peroxisome proliferatoractivated receptor γ (PPARγ) expression with GDM in overweight or obese women. Methods: One hundred and forty pregnant women with full-term single-birth cesarean-section were selected as the study subjects and grouped (70 GDM women, including 35 non-overweight/non-obese women [group G1] and 35 women with overweight or obesity [group G2]; 70 pregnant women with normal glucose tolerance, including 35 non-overweight/non-obese women [group N1] and 35 overweight/obese women [group N2]). The levels of serum VD, blood biochemistry, and adiponectin were compared in these women. Subcutaneous adipose tissue was isolated from the abdominal wall incision. VDR and PPARγ messenger RNA (mRNA) transcript levels in these adipose tissues were quantified by real-time polymerase chain reaction. The differences between the levels of PPARγ protein and phosphorylated PPARγ Ser273 were detected by Western blotting. Results: The serum VD level of GDM women was lower in comparison to that of women with normal glucose tolerance (G1 vs. N1: 20.62 ± 7.87 ng/mL vs. 25.85 ± 7.29 ng/mL, G2 vs. N2: 17.06 ± 6.74 ng/mL vs. 21.62 ± 7.18 ng/mL, P < 0.05), and the lowest in overweight/obese GDM women. VDR and PPARγ mRNA expression was higher in the adipose tissues of GDM women in comparison to that of women with normal glucose tolerance (VDR mRNA: G1 vs. N1: 210.00 [90.58-311.46] vs. 89.34 [63.74-159.92], G2 vs. N2: 298.67 [170.84-451.25] vs. 198.28 [119.46-261.23], PPARγ mRNA: G1 vs. N1: 100.72 [88.61-123.87] vs. 87.52 [66.37-100.04], G2 vs. N2: 117.33 [100.08-149.00] vs. 89.90 [76.95-109.09], P < 0.05), and their expression was the highest in GDM+ overweight/obese women. VDR mRNA levels positively correlated with the pre-pregnancy body mass index (BMI), pre-delivery BMI, fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and PPARγ mRNA while it negatively correlated with the VD and the adiponectin levels (r = 0.395, 0.336, 0.240, 0.190, 0.235, -0.350, -0.294, respectively, P < 0.05). The degree of PPARγ Ser273 phosphorylation increased in obese and GDM pregnant women. PPARγ mRNA levels positively correlated with pre-pregnancy BMI, pre-delivery BMI, FBG, HOMA-IR, serum total cholesterol, triglyceride, free fatty acid, and VDR mRNA, while it negatively correlated with the VD and adiponectin levels (r = 0.276, 0.199, 0.210, 0.230, 0.182, 0.214, 0.270, 0.235, -0.232, -0.199, respectively, P < 0.05). Conclusions: Both GDM and overweight/obese women had decreased serum VD levels and up-regulated VDR and PPARγ mRNA expression in adipose tissue, which was further higher in the overweight or obese women with GDM. VD may regulate the formation and differentiation of adipocytes through the VDR and PPARγ pathways and participate in the occurrence of GDM. Key words: Gestational diabetes mellitus; Overweight; Obesity; Serum vitamin D; Vitamin D receptor; Peroxisome proliferatoractivated receptor gamma

A novel macrocyclic amphiphile based on hybrid[4]arene containing tri(ethylene glycol) chains as the hydrophilic part and benzene rings as the hydrophobic part was synthesized. It self-assembled to produce nanoparticles and showed lower critical solution temperature behavior that was affected by its concentration and K

Background: Acitretin and matrine have been used in the treatment of psoriasis in China. This study was designed to investigate the role and related mechanisms of matrine alone and in combination with acitretin in the treatment of psoriasis in vitro and in vivo. Methods: HaCaT cells were treated with matrine at different concentrations of 0 (blank control), 0.2, 0.4, 0.8, and 1.6 mg/mL for 24, 48, 72 h, respectively. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium cell viability assay was used to assess the growth and proliferation of HaCaT cells. Cell cycle and apoptosis were detected by flow cytometry. Expression of protein was detected by Western blotting. Autophagy was observed by transmission electron microscopy. Then HaCaT cells were assigned to normal saline (NS) control group, matrine (0.4 mg/mL) group, acitretin (10 μmol/L) group, and matrine plus acitretin group, and the above methods were repeated. In animal experiments, the cumulative score (erythema, scaling, thickening) as a measure of the severity of inflammation was used to measure the skin performance of mice after treated with matrine 50 mg/kg, acitretin 4.5 mg/kg or combination of the two drugs on the psoriasis-like mouse models, respectively. Pathological findings of the lesions were observed, and the protein expressions in the lesions were detected by immunohistochemistry. Results: Cell proliferation inhibition was seen in HaCaT cells with treatment of matrine in a dose- and time-dependent manner (P < 0.01, respectively). Cell cycle G0/G1 phase arrest was observed in a dose-dependent way (P < 0.01). The expression of p21 (P < 0.05), LC3II/I (P < 0.01), and Beclin 1 (P < 0.01) increased and the expression of cyclin D1 (P < 0.05) decreased with increasing doses of matrine. Compared with the blank control, more autophagosomes were seen in HaCaT cells treated with matrine at 0.4 mg/mL by transmission electron microscopy (2.667 ± 1.202 vs. 21.33 ± 1.453, t = 9.899, P < 0.01). Cell proliferation inhibition and degree of the G0/G1 phase arrest was significantly higher in matrine plus acitretin group than those in matrine, acitretin, or the NS control group (P < 0.01, respectively). Compared with matrine or acitretin group, the expression of p21 (P < 0.05, P < 0.05) and LC3II/I (P < 0.01, P < 0.05) in matrine plus acitretin group increased significantly and the expression of cyclin D1 (P < 0.01, P < 0.05) and p62 (P < 0.05, P < 0.05) was reduced significantly. Compared with matrine or acitretin, matrine plus acitretin significantly down-regulated the phosphorylation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway (P < 0.05) and its downstream p-p70S6K (P < 0.05). In addition, the cumulative score of mice in the matrine plus acitretin group was significantly better than that in the matrine or acitretin group (1.480 ± 0.230 vs. 2.370 ± 0.241, P < 0.01; 1.480 ± 0.230 vs. 2.888 ± 0.341, P < 0.01). The expression of LC3 protein in the matrine plus acitretin group was also higher than that in the matrine, acitretin, or the NS control group (P < 0.05, respectively). Conclusions: Matrine has therapeutic potentials for psoriasis. Matrine and acitretin show synergistic effect via cell cycle arrest and autophagy induction by PI3K/Akt/mTOR pathway. Key words: Psoriasis; Autophagy; Phosphoinositide 3-kinase; Protein kinase B; Mammalian target of rapamycin

Background: Henoch-Schonlein purpura nephritis (HSPN) is a very common secondary kidney disease of childhood. Its pathogenesis and the treatment mechanism of glucocorticoid have not been fully elucidated. The aim of this study was to determine the relationship between p300 and the pathogenesis, glucocorticoid therapy in mice with HSPN, respectively. Methods: Forty-eight C57BL/6N male mice, weighing 18 to 20 g, were selected (3–4 weeks old, n = 8 per group). The mice in the normal control group (Group I) were given normal solvent and the HSPN model group (Group II) were given sensitizing drugs. The mice in Group III were injected intraperitoneally with dexamethasone after being given sensitizing drugs. Meanwhile, mice in Groups IV, V and VI with conditional knockout of p300 were also given normal solvent, sensitizing drugs and dexamethasone. The levels of serum IgA, creatinine, and circulating immune complex (CIC) concentrations, 24 h urinary protein and urinary erythrocyte in C57 wild mice, and p300 conditional knockout mice in each group were measured. The expression of p300 in renal tissues and the expression of glucocorticoid receptor (GR) α and β, transforming growth factor (TGF)-β1, and activator protein (AP)-1 after dexamethasone treatment were determined by real-time polymerase chain reaction and Western blotting. Results: Compared with the normal solvent control group (Group I), the expression of p300 mRNA in the model group (Group II) was significantly up-regulated. Western blotting further confirmed the result. Urinary erythrocyte count, 24 h urinary protein quantification, serum IgA, CIC, and renal pathologic score in Group V were distinctly decreased compared with non-knockout mice in Group II (9.7 ± 3.8 per high-power field [/HP] vs. 18.7 ± 6.2/HP, t = 1.828, P = 0.043; 0.18 ± 0.06 g/24 h vs. 0.36 ± 0.08 g/24 h, t = 1.837, P = 0.042; 18.78 ± 0.85 mg/mL vs. 38.46 ± 0.46 mg/mL, t = 1.925, P = 0.038; 0.80 ± 0.27 μg/mL vs. 1.64 ± 0.47 μg/mL, t = 1.892, P = 0.041; 7.0 ± 0.5 vs. 18.0 ± 0.5, t = 1.908, P = 0.039). Compared with non-knockout mice (Group III), the level of urinary erythrocyte count and serum IgA in knockout mice (Group VI) increased significantly after treatment with dexamethasone (3.7 ± 0.6/HP vs. 9.2 ± 3.5/HP, t = 2.186, P = 0.024; 12.38 ± 0.26 mg/mL vs. 27.85 ± 0.65 mg/mL, t = 1.852, P = 0.041). The expression level of GRα was considerably increased in the knockout group after dexamethasone treatment compared with non-knockout mice in mRNA and protein level (t = 2.085, P = 0.026; t = 1.928, P = 0.035), but there was no statistically significant difference in the expression level of GRβ between condition knockout and non-knockout mice (t = 0.059, P = 0.087; t = 0.038, P = 1.12). Furthermore, the expression levels of glucocorticoid resistance genes (AP-1 and TGF-β1) were notably increased after p300 knockout compared with non-knockout mice in mRNA and protein level (TGF-β1: t = 1.945, P = 0.034; t = 1.902, P = 0.039; AP-1: t = 1.914, P = 0.038; t = 1.802, P = 0.041). Conclusions: p300 plays a crucial role in the pathogenesis of HSPN. p300 can down-regulate the expression of resistance genes (AP-1 and TGF-β1) by binding with GRα to prevent further renal injury and glucocorticoid resistance. Therefore, p300 is a promising new target in glucocorticoid therapy in HSPN. Key words: p300; Henoch-Schonlein purpura nephritis; Pathogenesis; Glucocorticoid treatment

An environmental and sensitive sample pretreatment method was established and combined with high-performance liquid chromatography (HPLC) for the analysis of tetracycline hydrochloride (TC) in feed water and lake water. One element small molecule alcohol-salt aqueous two-phase system (ATPS) cannot effectively adjust the polarity of the system, but binary small molecule alcohol-salt ATPS can adjust the polarity and improve the extraction efficiency of antibiotics. In this work, a binary ATPS based on ethanol +2-propanol + (NH4 )2 SO4 system was formed and applied to the separation and purification of TC in real water samples. The influence factors on partition behaviors of TC were discussed, including the types and the concentration of phase salts, the volume ratio of alcohol, the pH value, extraction temperature, and the standing time. The response surface methodology was used to determine the best experimental conditions for multi-factor experiments. Under this optimal condition, the extraction efficiency of TC reached 95.7%. This new method is considered to have significant application in the divorce of antibiotics.

It was found that, among these chitosan@TiO2 (Cs@TiO2) composites calcined at different temperatures (200, 300, 400, 500 and 600 °C), the composite calcined at 300 °C (Cs@TiO2-300) showed the best adsorption and photocatalytic activity. To eliminate the limitation of recycling catalyst nanoparticles, the PDMS-SiO2-Cs@TiO2 composites with hydrophobic surfaces were prepared for dye degradation by embedding Cs@TiO2-300 nanoparticles into a PDMS-SiO2 sol-gel system. More concretely, with pumice stone as the support of composites, the experiment was carried out in a reaction bed. When pumice stones were used as supports for PDMS-SiO2-Cs@TiO2 composites, compared with its initial concentration, the concentration of dye solution decreased by 36% after 30 h of simulated sunlight irradiation. Additionally, the degradation efficiency of dyes hardly decreased after five cycles. The optical property and surface structure of PDMS-SiO2-Cs@TiO2 were characterized by UV–Vis DRS and XPS, respectively. It is noteworthy that the UV–Vis DRS results indicated that the light absorption range of both Cs@TiO2-300 composites and PDMS-SiO2-Cs@TiO2 composites had been broadened to the visible light region. Moreover, the XPS results indicated the existence of nitrogen (N) doped titanium on the surface of PDMS-SiO2-Cs@TiO2 composites.