Effect of mesencephalic astrocyte-derived neurotrophic factor on the inflammatory response in human gingival fibroblasts cells.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a unique member of the neurotrophic factor family residing in the endoplasmic reticulum, where it functions as a stress response protein maintaining endoplasmic reticulum homeostasis, in addition to being secreted extracellularly as a neurotrophic factor to bind with receptors to initiate intracellular signal transduction pathways. Interestingly, MANF has shown an important protective role in the inflammatory response of many diseases. In neural stem cells, pancreatic ß cells, and retinal cells, MANF can inhibit the inflammatory response, modulate the immune response, and promote tissue repair. However, the role of MANF in the periodontal inflammatory response remains unclear. In the present study, we used lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg) to establish a Pg-LPS-stimulated periodontal inflammatory model in human gingival fibroblasts cells (HGF-1) to investigate the role of MANF in vitro. We found that MANF could inhibit pro-inflammatory cytokine secretion, alleviate the endoplasmic reticulum stress response, promote cell survival, and inhibit cell apoptosis. Therefore, MANF might be a novel promising target for the treatment of periodontitis.

Covalent Microporous Polymer Nanosheets for Efficient Photocatalytic CO2 Conversion with H2 O.

It is still a challenging target to achieve photocatalytic CO2 conversion to valuable chemicals with H2 O as an electron donor. Herein, 2D imide-based covalent organic polymer nanosheets (CoPcPDA-CMP NSs), which integrate cobalt phthalocyanine (CoPc) moiety for reduction half-reaction and 3,4,9,10-perylenetetracarboxylic diimide moiety for oxidation half-reaction, are constructed as a Z-scheme artificial photosynthesis system to complete the overall CO2 reduction reaction. Owing to the outstanding light absorption capacity, charge separation efficiency, and electronic conductivity, CoPcPDA-CMP NSs exhibit excellent photocatalytic activity to reduce CO2 to CO using H2 O as a sacrificial agent with a CO production rate of 14.27 µmol g-1 h-1 and a CO selectivity of 92%, which is competitive to the state-of-the-art visible-light-driven organic photocatalysts towards the overall CO2 reduction reaction. According to a series of spectroscopy experiments, the authors also verify the photoexcited electron transfer processes in the CoPcPDA-CMP NSs photocatalytic system, confirming the Z-scheme photocatalytic mechanism. The present results should be helpful for fabricating high-performance organic photocatalysts for CO2 conversion.

Melatonin reduces nanoplastic uptake, translocation, and toxicity in wheat.

With increasing plastic production and consumption, large amounts of polystyrene nanoplastics are accumulated in soil due to improper disposal causing pollution and deleterious effects to environment. However, little information is available about how to alleviate the adverse impacts of nanoplastics on crops. In this study, the involvement of melatonin in modulating nanoplastic uptake, translocation, and toxicity in wheat plant was investigated. The results demonstrated that exogenous melatonin application reduced the nanoplastic uptake by roots and their translocation to shoots via regulating the expression of genes associated with aquaporin, including the upregulation of the TIP2-9, PIP2, PIP3, and PIP1.2 in leaves and TIP2-9, PIP1-5, PIP2, and PIP1.2 in roots. Melatonin activated the ROS scavenging system to maintain a better redox homeostasis and ameliorated the negative effects of nanoplastics on carbohydrate metabolism, hence ameliorated the plant growth and enhanced the tolerance to nanoplastics toxicity. This process was closely related to the exogenous melatonin application induced melatonin accumulation in leave. These results suggest that melatonin could alleviate the adverse effects of nanoplastics on wheat, and exogenous melatonin application might be used as a promising management strategy to sustain crop production in the nanoplastic-polluted soils.

LncRNA MAFG-AS1 regulates human periodontal ligament stem cell proliferation and Toll-like receptor 4 expression.

LncRNA MAFG-AS1 is predicted to interact with miR-146a, which can target Toll-like receptor 4 (TLR4), a key player in periodontitis. This study aimed to investigate the roles of MAFG-AS1 in periodontitis. It was observed that MAFG-AS1 was downregulated in the human periodontal ligament stem cells (PDLSCs) derived from periodontitis-affected teeth. Dual-luciferase assay revealed that co-transfection of MAFG-AS1 expression vector and miR-146a mimic showed significantly lower relative luciferase activity comparing to co-transfection of MAFG-AS1 expression vector and negative control (NC) miRNA. However, MAFG-AS1 and miR-146a failed to affect each other. Interestingly, MAFG-AS1 overexpression led to the upregulated TLR4. In addition, MAFG-AS1 overexpression also led to the inhibited proliferation of PDLSCs. Therefore, MAFG-AS1 may regulate the proliferation of PDLSCs and the expression of TLR4 to participate in periodontitis.

OSA-starch stabilized EPA nanoliposomes: Preparation, characterization, stability and digestion in vitro and in vivo.

OSA-starch stabilized EPA nanoliposomes (OSA-EPA-NLs) were prepared by thin film rehydration/dispersion method. The physical properties and morphology of OSA-EPA-NLs were characterized. The best formulated sample was used to measure the storage stability and oxidative properties of EPA under different environmental stresses and to determine release and absorption of OSA-EPA-NLs in vitro and in vivo. The results showed that the encapsulation efficiency of OSA-EPA-NLs was 84.61%. All samples were relatively stable under different environmental stresses, and the release rate of EPA in simulated intestine stage (89.87%) was higher than that in the simulated gastric stage (5.86%). The areas under the EPA concentration-time curve of OSA-EPA-NLs group and EPA-NLs group through in vivo study were 0.42 and 0.32, respectively, which indicated that OSA-starch could improve the stability of EPA nanoliposomes and enhance EPA bioavailability in the form of ethyl esters.

Low temperature tolerance is impaired by polystyrene nanoplastics accumulated in cells of barley (Hordeum vulgare L.) plants.

With increasing plastic consumption, the large amount of polystyrene nanoplastics (PS-NPs) in agricultural soil may not only directly affect the plant growth, but also indirectly affect the abiotic stress tolerance in crops. In this study, the barley (Hordeum vulgare L.) was irrigated with 2 g L-1 PS-NPs (65.776 ± 0.528 nm) solution for 7 days, then subjected to low temperature (2 â„ƒ) for 24 h. The imaging of protoplasts indicated that polymethylmethacrylate nanoplastics could across the cell wall and accumulate in plant cells. The PS-NPs significantly decreased Rubisco activities and ATP production, hence limiting the photosynthetic carbon assimilation in barley under low temperature. The PS-NPs accumulated in cells also caused the significantly decreased activities of key enzymes involved in sucrolytic, glycolysis and starch metabolism pathways, including UDP-glucose pyrophorylase, ADP-Glucose pyrophosphorylase, phosphoglucomutase, glucose-6-phosphate dehydrogenase, phosphoglucoisomerase, fructokinase and phosphofructokinase. In addition, under low temperature, the PS-NPs presence significantly reduced the activities of superoxide dismutase, ascorbate peroxidase and catalase in chloroplasts, and significantly reduced the activities of ascorbate peroxidase and catalase in mitochondria. Thus, it is suggested that the PS-NPs accumulated in plant cells impaired the low temperature tolerance in barley mainly by the negative effects on photosynthetic carbon assimilation, carbohydrate metabolism and ROS homeostasis in sub-cellular level.

Identification a novel de novo RUNX2 frameshift mutation associated with cleidocranial dysplasia.

BACKGROUND: Cleidocranial dysplasia (CCD) is a rare genetic disorder affecting bone and cartilage development. Clinical features of CCD comprise short stature, delayed ossification of craniofacial structures with numerous Wormian bones, underdeveloped or aplastic clavicles and multiple dental anomalies. Several studies have revealed that CCD development is strongly linked with different mutations in runt-related transcription factor 2 (RUNX2) gene. OBJECTIVE: Identification and functional characterization of RUNX2 mutation associated with CCD. METHODS: We performed genetic testing of a patient with CCD using whole exome sequencing and found a novel RUNX2 frameshift mutation: c.1550delT in a sporadic case. We also compared the functional activity of the mutant and wild-type RUNX2 through immunofluorescence microscopy and osteocalcin promoter luciferase assay. RESULTS: We found a novel RUNX2 frameshift mutation, c.1550delT (p.Trp518Glyfs*60). Both mutant RUNX2 and wild-type RUNX2 protein were similarly confined in the nuclei. The novel mutation caused abrogative transactivation activity of RUNX2 on osteocalcin promoter. CONCLUSIONS: We explored a novel RUNX2 deletion/frameshift mutation in a sporadic CCD patient. This finding suggests that the VWRPY domain may play a key role in RUNX2 transactivation ability.

A novel system of artificial antigen-presenting cells efficiently stimulates Flu peptide-specific cytotoxic T cells in vitro.

Therapeutic numbers of antigen-specific cytotoxic T lymphocytes (CTLs) are key effectors in successful adoptive immunotherapy. However, efficient and reproducible methods to meet the qualification remain poor. To address this issue, we designed the artificial antigen-presenting cell (aAPC) system based on poly(lactic-co-glycolic acid) (PLGA). A modified emulsion method was used for the preparation of PLGA particles encapsulating interleukin-2 (IL-2). Biotinylated molecular ligands for recognition and co-stimulation of T cells were attached to the particle surface through the binding of avidin-biotin. These formed the aAPC system. The function of aAPCs in the proliferation of specific CTLs against human Flu antigen was detected by enzyme-linked immunospot assay (ELISPOT) and MTT staining methods. Finally, we successfully prepared this suitable aAPC system. The results show that IL-2 is released from aAPCs in a sustained manner over 30 days. This dramatically improves the stimulatory capacity of this system as compared to the effect of exogenous addition of cytokine. In addition, our aAPCs promote the proliferation of Flu antigen-specific CTLs more effectively than the autologous cellular APCs. Here, this aAPC platform is proved to be suitable for expansion of human antigen-specific T cells.

Enhanced enzymatic saccharification of sorghum straw by effective delignification via combined pretreatment with alkali extraction and deep eutectic solvent soaking.

Hydrogen bond donor (HBD) in ChCl-based deep eutectic solvent (DESs) had significant influence on the Sorghum straw (SS) pretreatment. Lactic acid (LAC) was chosen as the appropriate HBD for preparing ChCl-based DES to pretreat Sorghum straw (SS). Furthermore, sequential pretreatment with dilute sodium hydroxide (0.75 wt%) for 1 h at 121 °C and ChCl:LAC soaking at 140 °C for 40 min was applied to pretreat SS for removing lignin (78.4%) and xylan (67.6%). Hydrolysis for 72 h, the reducing sugar yield reached 94.9%. Moreover, relationships of delignification and xylan removal with saccharification were explored after pretreatment. Finally, the fermentability of SS-hydrolysates was verified by bioethanol fermentation by S. cerevissiae with the yield of 0.45 g ethanol/g glucose. No significant inhibition was observed on ethanol fermentation. Obviously, establishment of high-efficient combination pretreatment with alkali extraction and ChCl:LAC soaking was successfully demonstrated for enhancing enzymatic saccharification of SS.

Antibacterial Properties of Small-Size Peptide Derived from Penetratin against Oral Streptococci.

Periodontitis, an infectious disease originating from dental biofilms that causes the irreversible loss of alveolar bone, is accompanied by gradual biofilm formation and the continuous progression of inflammation. A small peptide derived from penetratin, Arg-Gln-Ile-Arg-Arg-Trp-Trp-Gln-Arg-NH2 (RR9), appears to have antibacterial properties against selected strains associated with periodontitis. The purpose of this research is to assess the antibacterial activity and mechanism of RR9 against the initial oral colonizers Streptococci oralis, Streptococci gordonii, and Streptococci sanguinis and to investigate the cytotoxicity of RR9 on human gingival fibroblasts in vitro. The effects of RR9 on the initial oral settlers of planktonic and biofilm states were evaluated by measuring the MIC, MBC, bactericidal kinetics, and antibiofilm activity. Visual evidence and antibacterial mechanisms were identified, and the anti-inflammatory activity and cytotoxicity were measured. The results demonstrated that RR9 can inhibit the growth of streptococci in the planktonic state and during biofilm formation in vitro while keeping a low toxicity against eukaryotic cells. The antibacterial mechanism was proven to be related to the lower expression of sspA in streptococci. RR9 may be used as a potential antimicrobial and anti-infective agent for periodontal disease.

Polystyrene microplastics disturb the redox homeostasis, carbohydrate metabolism and phytohormone regulatory network in barley.

As emerging contaminants, microplastics (mPS, <5 mm) have been reported to adversely affect the plant growth; however, the mechanisms of mPS-induced growth limitation are rarely known. Here, it was found that the plastic particles were absorbed and accumulated in barley plants, which limited the development of rootlets. The mPS-treated plants had significantly higher concentrations of H2O2 and O2- in roots than the control. The mPS significantly increased the activities of dehydroascorbate reductase, glutathione reductase, ADP-Glucose pyrophosphorylase, fructokinase and phosphofructokinase, while decreased the activities of cell wall peroxidase, vacuolar invertase, sucrose synthase, phosphoglucomutase, glucose-6-phosphate dehydrogenase and phosphoglucoisomerase in roots. The changes in activities of carbohydrate and ROS metabolism enzymes in leaves showed a different trend from that in roots. The mPS plants possessed a higher trans-zeatin concentration while lower concentrations of indole-3-acetic acid, indole-3-butyric acid and dihydrozeatin than the control plants in leaves. However, the phytohormone changes in roots were distinct from those in leaves under mPS. In addition, significant correlations between enzyme activities and phytohormone concentrations were found. It was suggested that the phytohormone regulatory network plays key roles in regulating the activities of key enzymes involved in carbohydrate and ROS metabolisms in response to mPS in barley.

Enzymatic in situ saccharification of chestnut shell with high ionic liquid-tolerant cellulases from Galactomyces sp. CCZU11-1 in a biocompatible ionic liquid-cellulase media.

In this study, it was the first time to report that the cellulases of Galactomyces sp. CCZU11-1 showed high activity and stability in the culture and reaction media containing IL [Mmim]DMP. Using untreated chestnut shell (CNS) as carbon source in the culture media containing IL [Mmim]DMP (5%, w/v), high activity of FPA (28.6U/mL), xylanase (186.2U/mL), and CMCase (107.3U/mL) were obtained, and 184.9mg/L of total protein was achieved. Furthermore, the changes in the structural features (crystallinity, morphology, and porosity) of the solid residue of CNS utilized with Galactomyces sp. CCZU11-1 were characterized with Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction. After was enzymatically hydrolyzed with the prepared crude enzymes in IL diluted to 20% (w/v), a high yield of reducing sugars, 62.1%, was obtained. Significantly, Galactomyces sp. CCZU11-1 showed high potential for the efficient transformation of lignocellulosic materials to glucose in a single-step process.

Whole-exome sequencing identifies variants in invasive pituitary adenomas.

Pituitary adenomas exhibit a wide range of behaviors. The prediction of invasion or malignant behavior in pituitary adenomas remains challenging. The objective of the present study was to identify the genetic abnormalities associated with invasion in sporadic pituitary adenomas. In the present study, the exomes of six invasive pituitary adenomas (IPA) and six non-invasive pituitary adenomas (nIPA) were sequenced by whole-exome sequencing. Variants were confirmed by dideoxynucleotide sequencing, and candidate driver genes were assessed in an additional 28 pituitary adenomas. A total of 15 identified variants were mainly associated with angiogenesis, metabolism, cell cycle phase, cellular component organization, cytoskeleton and biogenesis immune at a cellular level, including 13 variants that occurred as single nucleotide variants and 2 that comprised of insertions. The messenger RNA (mRNA) levels of diffuse panbronchiolitis critical region 1 (DPCR1), KIAA0226, myxovirus (influenza virus) resistance, proline-rich protein BstNI subfamily 3, PR domain containing 2, with ZNF domain, RIZ1 (PRDM2), PR domain containing 8 (PRDM8), SPANX family member N2 (SPANXN2), TRIO and F-actin binding protein and zinc finger protein 717 in IPA specimens were 50% decreased compared with nIPA specimens. In particular, DPCR1, PRDM2, PRDM8 and SPANXN2 mRNA levels in IPA specimens were approximately four-fold lower compared with nIPA specimens (P=0.003, 0.007, 0.009 and 0.004, respectively). By contrast, the mRNA levels of dentin sialophospho protein, EGF like domain, multiple 7 (EGFL7), low density lipoprotein receptor-related protein 1B and dynein, axonemal, assembly factor 1 (LRRC50) were increased in IPA compared with nIPA specimens (P=0.041, 0.037, 0.022 and 0.013, respectively). Furthermore, decreased PRDM2 expression was associated with tumor recurrence. The findings of the present study indicate that DPCR1, EGFL7, the PRDM family and LRRC50 in pituitary adenomas are modifiers of tumorigenesis, and most likely contribute to the development of oncocytic change and to the invasive tumor phenotype.

Enzymatic saccharification of sugarcane bagasse by N-methylmorpholine-N-oxide-tolerant cellulase from a newly isolated Galactomyces sp. CCZU11-1.

Based on the enrichment culture strategy, a novel N-methylmorpholine-N-oxide (NMMO)-tolerant cellulase-producing strain Galactomyces sp. CCZU11-1 was isolated from soil samples. After the optimization of culture condition, the highest FPA (13.4 U/mL) and CMCase (24.5 U/mL) were obtained. In both culture and reaction media containing NMMO 25% (w/v), the cellulase from Galactomyces sp. CCZU11-1 still had good activity. Furthermore, high saccharification rate was obtained in aqueous-NMMO media. Moreover, the fermentability of the hydrolyzates, obtained after enzymatic in situ saccharification of the NMMO-pretreated sugarcane bagasse, was evaluated using Saccharomyce scerevisiae. In conclusion, Galactomyces sp. CCZU11-1 is a promising candidate as high NMMO-tolerant cellulase producer and has potential application in future.