Huntingtin-associated protein 1 is a potential tumor suppressor for gastric cancer.

BACKGROUND: Gastric cancer is heterogeneous cancer and the causes of this disease are complex. New diagnostic and therapeutic targets are urgently needed to explore. Huntingtin-associated protein 1 (HAP1) is directly related to Huntington's disease (HD). However, patients with Huntington's disease have a lower incidence of cancer. Therefore, we are committed to studying the correlation between HAP1 and gastric carcinogenesis and development. METHODS AND RESULTS: Immunohistochemical staining, western blot analysis, and RT-qPCR were conducted to explore the localization and expression of HAP1 in gastric cancer. To study the biological significance of HAP1, we overexpressed HAP1 in both MKN28 and AGS cell lines by lentivirus infection. To explore the role of HAP1 in cell proliferation, the cells counting assay, EdU incorporation assay, and colony formation assay were carried out. We performed the wound healing assay and transwell assay to study the cell migration and invasion. To further investigate whether HAP1 could regulate gastric cancer cell death during glucose deprivation, Annexin V-FITC/PI staining was performed. In our study, we elucidated that HAP1 was downregulated in gastric cancer. What's more, overexpressing HAP1 inhibited cell proliferation, cell migration and invasion, and triggered apoptosis during glucose deprivation. More importantly, the antitumor properties and mechanisms of HAP1 have been elucidated further in gastric cancer. CONCLUSIONS: Taken together, the available evidence implies that HAP1 may serve as a potential tumor suppressor, making it a significant target in preventing and treating gastric cancer. This research provides a theoretical basis for the early diagnosis, clinical targeted therapy, and prognosis evaluation of gastric cancer.

Hypoxia regulates angeogenic-osteogenic coupling process via up-regulating IL-6 and IL-8 in human osteoblastic cells through hypoxia-inducible factor-1α pathway.

Inappropriate angiogenesis and osteogenesis are considered as the crucial factors of osteoporotic fracture. Hypoxia is a primary driving force for regulating the angiogenic-osteogenic coupling process. Our recent results indicated that hypoxia could improve angiogenesis as well as differentiation and activity of osteoblastic cells via up-regulating VEGF through HIF-1α pathway. Here we demonstrated that in human osteoblastic MG-63, U2-OS and Saos-2 cells, besides VEGF, the other two pro-angiogenic factors IL-6 and IL-8 were also up-regulated by hypoxia and CoCl2 (a mimic of hypoxia). Mechanism studies indicated overexpression of HIF-1α (generated from transfection with a plasmid encoding sense HIF-1α) markedly increased the levels of IL-6 and IL-8 in osteoblastic cells. Furthermore, a luciferase reporter assay was performed using the reporter vector containing the IL-6 or IL-8 promoter sequence to illustrate observably increased activity of hypoxia-induced IL-6 and IL-8 promoter caused by overexpression of HIF-1α. Additionally, chromatin immune-precipitation analysis showed hypoxia increased the DNA binding ability of HIF-1α to IL-6 or IL-8 promoter. Analysis in vitro by MTT test and Boyden chamber assay showed exogenous IL-6 and IL-8 (a relatively short period of treatment with recombinant IL-6 or IL-8 equivalent to the autocrine levels) could significantly promote the proliferation of human osteoblastic, endothelial and monocytic cells, as well as the migration of human endothelial cells. Taken together, these results indicate that IL-6 and IL-8 in osteoblastic cells may also contribute to the angiogenic-osteogenic coupling process via HIF-1α pathway. Besides VEGF, IL-6- or IL-8-targeted adjunctive therapy maybe a new strategy to improve the treatment of osteoporosis.

Phase-dependent Fano-shape optomechanically induced transparency.

We present a detailed study of a three-mode-coupling cavity optomechanical system where one mechanical mode and two optical whispering-gallery modes are coupled together. We extend the earlier investigation of regular optomechanically induced transparency (OMIT) [Science330, 1520 (2010)SCIEAS0036-807510.1126/science.1195596] in a more general case. A complete analytical description of the present system is obtained, and quantitative analyses of the Fano-shape OMIT spectrum are provided. It is clearly shown that a sharp and asymmetric Fano-shape OMIT lineshape, which is decided by the phase difference between the probe field and the mechanical driving, can be observed from the probe output.

Salidroside accelerates fracture healing through cell-autonomous and non-autonomous effects on osteoblasts.

Salidroside (SAL), a major active component of Rhodiola rosea L., exhibits diverse pharmacological effects. However, the direct roles of SAL in fracture healing remain largely unknown. Here, we demonstrate that SAL significantly promotes proliferation by altering the cell-cycle distribution of osteoblastic cells. SAL also greatly stimulates osteoblast differentiation and mineralization by inducing the expression of Runx2 and Osterix. In addition to its osteoblast-autonomous effects, SAL can activate the HIF-1α pathway coupling of angiogenesis and osteogenesis through cell-non-autonomous effects. Our in vitro results suggest that SAL significantly up-regulates HIF-1α expression at the mRNA and protein levels. Furthermore, the nuclear translocation and transcriptional activity of HIF-1α and the HIF-responsive gene VEGF increase following SAL treatment. Our mechanistic study revealed that the regulation of osteoblastic proliferation and HIF-1α expression partly involves MAPK/ERK and PI3K/Akt signaling. Our in vivo analysis also demonstrated that SAL can promote angiogenesis within the callus and accelerate fracture healing. Thus, SAL promotes skeletal regeneration in cell-autonomous and cell-non-autonomous ways and might be a potential therapy for accelerating fracture healing.

Biological function of hpsh4590 localized in the plasticity zone of Helicobacter pylori.

The aim of this study was to determine the biological function of hpsh4590 in Helicobacter pylori. After Hpsh4590 was expressed using a prokaryotic expression system, the cytotoxic effects and IL-8 production of Hpsh4590 were analyzed by co-culturing with GES-1 cells. Meanwhile, the antibody of rHpsh4590, produced by immunizing rabbit, was used for localization and protein interaction studies. Hpsh4590 fusion protein was expressed successfully in Escherichia coli Rosetta (DE3), and the polyclonal antibody was produced at high titers. The MTT assay showed that the inhibition ratio of GES-1 cells cultured with 0.1 µg/mL rHpsh4590 (3.02% ± 0.02%) was significantly lower than that of 20 µg/mL rHpsh4590 (57.57% ± 0.03%, p < 0.01), while DAPI staining showed the cytotoxic effects of rHpsh4590 for GES-1 cells. The up-regulation of cleaved caspase-3 and cleaved PARP was observed after GES-1 cells co-cultured with rHpsh4590 by Western blot. Co-culturing of GES-1 cells with rHpsh0459 (20 µg/mL) led to significant production of IL-8 at 12 h(1097.74 ± 212.37 pg/mL) and 24 h (1379.55 ± 209.58 pg/mL) then at 6 h(134.68 ± 14.64 pg/mL, p < 0.01). These observations suggest that the cytotoxicity of Hpsh4590 occurred in a concentration dependent manner, which is related with IL-8 secretion from gastric mucosal epithelial cells. Hpsh4590 was found localized in the membrane and the periplasm of H. pylori, interacted with zinc finger protein and methionine ABC transporter ATP-binding protein, and potentially regulates DNA uptake or transfer.

Effective ciprofloxacin cationic antibacterial agent against persister bacteria with low hemolytic toxicity.

With the widespread use of antibiotics, bacterial resistance has developed rapidly. To make matters worse, infections caused by persistent bacteria and biofilms often cannot be completely eliminated, which brings great difficulties to clinical medication. In this work, three series of quinolone pyridinium quaternary ammonium small molecules were designed and synthesized. Most of the compounds showed good antibacterial activity against Gram-positive bacteria (S. aureus and E. faecalis) and Gram-negative bacteria (E. coli and S. maltophilia). The activity of the para-pyridine quaternary ammonium salt was better than that of the meta-pyridine. 3f was the optimal compound with good stability in body fluids and was unlikely to induce bacterial resistance. The hemolysis rate of erythrocytes at 1280 µg/mL for 3f was only 5.1%. Encouragingly, 3f rapidly killed bacteria within 4 h at 4 × MIC concentration and was effective in killing persistent bacteria in biofilms. The antibacterial mechanism experiments showed that 3f could cause disorder of bacterial membrane potential, increase bacterial membrane permeability, dissolve and destroy the membrane. Incomplete bacterial membranes lead to leakage of bacterial genetic material, concomitant production of ROS, and bacterial death due to these multiple effects.

Recent advances in the exploration of oxazolidinone scaffolds from compound development to antibacterial agents and other bioactivities.

Bacterial infections cause a variety of life-threatening diseases, and the continuous evolution of drug-resistant bacteria poses an increasing threat to current antimicrobial regimens. Gram-positive bacteria (GPB) have a wide range of genetic capabilities that allow them to adapt to and develop resistance to practically all existing antibiotics. Oxazolidinones, a class of potent bacterial protein synthesis inhibitors with a unique mechanism of action involving inhibition of bacterial ribosomal translation, has emerged as the antibiotics of choice for the treatment of drug-resistant GPB infections. In this review, we discussed the oxazolidinone antibiotics that are currently on the market and in clinical development, as well as an updated synopsis of current advances on their analogues, with an emphasis on innovative strategies for structural optimization of linezolid, structure-activity relationship (SAR), and safety properties. We also discussed recent efforts aimed at extending the activity of oxazolidinones to gram-negative bacteria (GNB), antitumor, and coagulation factor Xa. Oxazolidinone antibiotics can accumulate in GNB by a conjugation to siderophore-mediated ß-lactamase-triggered release, making them effective against GNB.

Design, synthesis and antibacterial evaluation of low toxicity amphiphilic-cephalosporin derivatives.

Global public health is facing a serious problem as a result of the rise in antibiotic resistance and the decline in the discovery of new antibiotics. In this study, two series of amphiphilic-cephalosporins were designed and synthesized, several of which showed good antibacterial activity against both Gram-positive and Gram-negative bacteria. Structure-activity relationships indicated that the length of the hydrophobic alkyl chain significantly affects the antibacterial activity against Gram-negative bacteria. The best compound 2d showed high activity against drug-susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) with MICs of 0.5 and 2-4 µg/mL, respectively. Furthermore, 2d remained active in complex mammalian body fluids and had a longer post-antibiotic effect (PAE) than vancomycin. Mechanism studies indicated that compound 2d lacks membrane-damaging properties and can target penicillin-binding proteins to disrupt bacterial cell wall structure, inhibit the metabolic activity and induce the accumulation of reactive oxygen species (ROS) in bacteria. Compound 2d showed minimal drug resistance and was nontoxic to HUVEC and HBZY-1 cells with CC50 > 128 µg/mL. These findings suggest that 2d is a promising drug candidate for treating bacterial infections.

[ESX-1 secreted protein ESAT-6 of Mycobacterium tuberculosis enhances the phagocytosis of RAW264.7 macrophages].

OBJECTIVE: To investigate the effects of Mycobacterium tuberculosis ESX-1 protein early secreted antigenic target of 6 kDa (ESAT-6) in modulating phagocytosis of RAW264.7 cells. METHODS: RAW264.7 cells were transfected with recombinant plasmids pFLAG-ESAT-6 and pFLAG-EGFP by liposome. After screening with a high level of G418, the macrophage cell lines stably expressing flag-ESAT-6 or flag-EGFP proteins were obtained. The cell lines were further identified by PCR, RT-PCR and western blot. The phagocytosis of those cell lines was analyzed for ingested fluorescent beads by flow cytometry and for phagocytized Escherichia coli (E. coli) by colony count and confocalmicroscopy. RESULTS: We established successfully RAW-E6 cell line stably expressing flag-ESAT-6 and RAW-EGFP cell line stably expressing flag-EGFP. Flow cytometric analysis shows that the percentage of phagocytosis of RAW-E6 was higher than that of RAW264.7 and RAW-EGFP. Colony count and confocal microscopy test also show that RAW-E6 had higher phagocytosis ability than RAW264.7 and RAW-EGFP. CONCLUSION: The secreted protein ESAT-6 can enhance the phagocytosis of macrophages, which provides new evidence to understand the pathogenesis of Mycobacterium tuberculosis.

Identification and validation of a novel ubiquitination-related gene UBE2T in Ewing's sarcoma.

Background: Ewing's sarcoma (ES) is one of the most prevalent malignant bone tumors worldwide. However, the molecular mechanisms of the genes and signaling pathways of ES are still not well sufficiently comprehended. To identify candidate genes involved in the development and progression of ES, the study screened for key genes and biological pathways related to ES using bioinformatics methods. Methods: The GSE45544 and GSE17618 microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. A protein-protein interaction (PPI) network was built, and key module analysis was performed using STRING and Cytoscape. A core-gene was gained and was validated by the validation dataset GSE67886 and immunohistochemistry (IHC). The diagnostic value and prognosis evaluation of ES were executed using, respectively, the ROC approach and Cox Regression. Results: A total of 187 DEGs, consisting of 56 downregulated genes and 131 upregulated genes, were identified by comparing the tumor samples to normal samples. The enriched functions and pathways of the DEGs, including cell division, mitotic nuclear division, cell proliferation, cell cycle, oocyte meiosis, and progesterone-mediated oocyte maturation, were analyzed. There were 149 nodes and 1246 edges in the PPI network, and 15 hub genes were identified according to the degree levels. The core gene (UBE2T) showed high expression in ES, validated by using GSE67886 and IHC. The ROC analysis revealed UBE2T had outstanding diagnostic value in ES (AUC = 0.75 in the training set, AUC = 0.90 in the validation set). Kaplan-Meier (analysis of survival rate) and Cox Regression analyses indicated that UBE2T was a sign of adverse results for sufferers with ES. Conlusion: UBE2T was a significant value biomarker for diagnosis and treatment of ES, thereby presenting a novel potential therapeutic target for ES as well as a new perspective for assessing the effect of treatment and prognostic prediction.

Downregulation of miR­7 and miR­153 is involved in Helicobacter pylori CagA induced gastric carcinogenesis and progression.

Helicobacter pylori (H. pylori) infection plays a pivotal role in the development of gastric cancer (GC). However, the association between aberrant microRNAs (miRNAs/miRs) expression and H. pylori­induced GC remains poorly understood. The present study reported that repeated infection of H. pylori caused the oncogenicity of GES­1 cells in BALB/c Nude mice. miRNA sequencing revealed that both miR­7 and miR­153 were significantly decreased in the cytotoxin­associated gene A (CagA) positive GC tissues and this was further confirmed in a chronic infection model of GES­1/HP cells. Further biological function experiments and in vivo experiments validated that miR­7 and miR­153 can promote apoptosis and autophagy, inhibit proliferation and inflammatory response in GES­1/HP cells. All the associations between miR­7/miR­153 and their potential targets were revealed via bioinformatics prediction and dual­luciferase reporter assay. Particularly, downregulation of both miR­7 and miR­153 obtained an improved sensitivity and specificity in diagnosing H. pylori (CagA+)­induced GC. The present study identified that the combination of miR­7 and miR­153 may be regarded as novel therapeutic targets in H. pylori CagA (+)­associated GC.

Interleukin-8 secretion by ovarian cancer cells increases anchorage-independent growth, proliferation, angiogenic potential, adhesion and invasion.

It has been shown that IL-8 is elevated in ovarian cyst fluid, ascites, serum, and tumor tissue from ovarian cancer (OVCA) patients, and increased IL-8 expression correlates with poor prognosis and survival. However, the exact role that IL-8 plays in this malignancy or whether IL-8 can regulate malignant behavior has not been established. Here we demonstrate that overexpression of IL-8 in non-IL-8-expressing A2780 cells (by transfecting with plasmid encoding for sense IL-8) increases anchorage-independent growth, proliferation, angiogenic potential, adhesion and invasion while depletion of endogenous IL-8 expression in IL-8-overexpressing SKOV-3 cells (by transfecting with plasmid encoding for antisense IL-8) decreases the above effects. Further investigation indicates that IL-8-stimulated cell proliferation correlates with alteration of cell cycle distribution by increasing levels of cell cycle-regulated Cyclin D1 and Cyclin B1 proteins as well as activation of PI3K/Akt and Raf/MEK/ERK, whereas IL-8-enhanced OVCA cell invasive correlates with increased MMP-2 and MMP-9 activity and expression. Our data suggest that IL-8 secreted by OVCA cells promotes malignant behavior of these cells via inducing intracellular molecular signaling. Therefore, modulation of IL-8 expression or its related signaling pathway may be a promising strategy for controlling the progression and metastasis of OVCA.

[The clinical research on the application of the heating humidifier with heating wire in pipeline in patients with tracheal intubation].

OBJECTIVE: To explore the effect of the heating humidifier with heating wire in pipeline in patients with tracheal intubation. METHODS: The present research was a prospective study. One hundred and twenty patients with tracheal intubation and mechanical ventilation who could not reach the indication of extubation after weaning were randomly divided into two groups. The patients in the control group (n = 60) were treated by routine airway management which was intermittent airway instillation with normal saline to humidify the airway, and those in the experimental group(n = 60) were used heating humidifier with heating wire in pipeline for airway humidification. The temperature and humidity of inhaled gas, sputum viscosity, the number of tracheal catheter with sputum scab after extubation, as well as number of reintubated cases due to tube plugging, and the oxygenation index at different time points after oxygen inhalation were recorded. RESULTS: The temperature and humidity of inhaled gas in experimental group were higher than those in control group [temperature (centigrade): 36.9 ± 0.2 vs. 22.3 ± 2.1, humidity (mg/L): 44.0 ± 2.0 vs. 27.0 ± 4.0, both P < 0.01]. The number of sputum viscosity II (humidification in well) in experimental group was significantly more than that in the control group (49 vs. 15), but the number of sputum viscosity III (humidification in sufficient) in experimental group was significantly less than that in the control group (8 vs. 43, both P < 0.05). The number of tracheal catheter with sputum scab after extubation (5 cases) and reintubation for tracheal catheter plugging (0 case) in experimental group were significantly less than those in the control group (24 cases, 6 cases, P < 0.01). The oxygenation index (mm Hg, 1 mm Hg = 0.133 kPa) in experimental group was increased after oxygen inhalation, and higher than that in control group at 96 hours and 120 hours (96 hours: 349.0 ± 21.3 vs. 290.0 ± 20.7, 120 hours: 354.0 ± 25.6 vs. 309.0 ± 22.6, both P < 0.01). CONCLUSIONS: The humidify of heating humidifier with heating wire in pipeline for airway humidification in patients with tracheal intubation was better than that of intermittent airway instillation with normal saline.

Autocrine production of interleukin-8 confers cisplatin and paclitaxel resistance in ovarian cancer cells.

It has been widely reported that interleukin-8 (IL-8) is overexpressed in ovarian cyst fluid, ascites, serum, and tumor tissue from ovarian cancer (OVCA) patients, and elevated IL-8 expression correlates with a poor final outcome and chemosensitivity. However, the role of IL-8 expression in the acquisition of the chemoresistance phenotype and the underlining mechanisms of drug resistance in OVCA cells are not yet fully understood. Here we show that both exogenous (a relatively short period of treatment with recombination IL-8) and endogenous IL-8 (by transfecting with plasmid encoding for sense IL-8) induce cisplatin and paclitaxel resistance in non-IL-8-expressing A2780 cells, while deleting of endogenous IL-8 expression in IL-8-overexpressing SKOV-3 cells (by transfecting with plasmid encoding for antisense IL-8) promotes the sensitivity of these cells to anticancer drugs. IL-8-mediated resistance of OVCA cells exhibits decreased proteolytic activation of caspase-3. Meanwhile, the further study demonstrates that the chemoresistance caused by IL-8 is associated with increased expression of both multidrug resistance-related genes (MDR1) and apoptosis inhibitory proteins (Bcl-2, Bcl-xL, and XIAP), as well as activation of PI3K/Akt and Ras/MEK/ERK signaling. Therefore, modulation of IL-8 expression or its related signaling pathway may be a promising strategy of treatment for drug-resistant OVCA.

[Experimental study on Raman spectroscopy of alkane gases in simulated deep-sea extreme environments].

In the present work, Raman spectra of alkane gases aqueous solution under simulated deep-sea hydrothermal environment were acquired by high temperature and high pressure deep-sea simulation experiment system. The variation laws of the Raman spectral features with various temperature and pressure were analyzed and mathematical model between them were established. The results show that for all Raman peaks of these alkane gases in aqueous solution the frequency is lower than gaseous state because of hydrogen bond; the variations of their Raman spectrum were not obvious as the pressure increased (< or = 40 MPa) in room temperature; and all peak positions move to lower wave number and their full width at half maximum (FWHM) increased along with changing temperature in the range of room temperature to 350 degrees C at 40 MPa pressure. The results provide an experimental basis for the in-situ detection of deep sea by Raman laser spectroscopy system in hydrothermal environment.

The value of Angipoietin-2 as a biomarker for the prognosis of osteosarcoma: A protocol for systematic review and meta-analysis.

BACKGROUND: The function of Angipoietin-2 (Agn2) in osteosarcoma has not been fully explored and exists controversial. Therefore, we conducted a meta-analysis to investigate the role of Agn2 in the prognosis of osteosarcoma. In addition, bioinformatics analysis was carried out to reveal the mechanism and related pathways of Agn2 in osteosarcoma. METHODS: Literature search was operated on databases up to July 2021, including PubMed, Web of Science, China National Knowledge Infrastructure, China Biology Medicine disc, and Wan Fang Data. The relation between Agn2 expression and survival outcome was estimated by hazard ratio and 95% confidence interval. Meta-analysis was performed on the Stata 16.0. Being obtained from The Cancer Genome Atlas, the original data were used to further verify the prognostic role of Agn2 in osteosarcoma. Gene set enrichment analysis was applied to predict the potential mechanism of Agn2. The correlation between Agn2 and osteosarcoma immune infiltration was analyzed by TIMER database. RESULTS: The results of this meta-analysis would be submitted to peer-reviewed journals for publication. CONCLUSION: This study will provide evidence for the exploration of the relationship between Agn2 and the prognosis of osteosarcoma and its mechanism. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results will be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/GWQ53.

Insight into the influence of donor-acceptor system on graphitic carbon nitride nanosheets for transport of photoinduced charge carriers and photocatalytic H2 generation.

The rapid recombination of photogenerated charges is one of the main restriction for promoting the photocatalytic H2 generation of graphitic carbon nitride (CN) material. Herein, donor-acceptor (D-A) system was introduced into CN nanosheets by oxygen and/or phenyl doping (DA-CN) strategy to facilitate the transport of photoinduced charge carriers and H2 generation. Experimental and theoretical results revealed that the nanosheet structure of DA-CN shortened the photoexcited charges transport length to the surface, and the D-A system embedded in DA-CN provided the dipole-induced internal electric field for charges transport. As a consequence, compared with pristine CN, DA-CN samples performed the improved transport of photogenerated charges and photocatalytic H2 evolution. Notably, DA-CN-OP (oxygen and phenyl co-doping) with the strongest dipole-induced internal electric field originated from D-A system displayed the highest photocatalytic H2 evolution rate at 7.394 mmol g-1h-1, which was 7.67 times as that of pristine CN (0.964 mmol g-1h-1). This work not only provides a simple strategy to construct highly efficient CN nanosheet photocatalyst with D-A system, but also promote the deep insight into the effect of molecular dipole originated from D-A system on the transport of photoinduced charge carriers and photocatalytic activity for CN material.

Phenyl-Bridged Graphitic Carbon Nitride with a Porous and Hollow Sphere Structure to Enhance Dissociation of Photogenerated Charge Carriers and Visible-Light-Driven H2 Generation.

Graphitic carbon nitride (CN) suffers from rapid recombination of photoexcited charges due to the existing highly symmetrical tri-s-triazine ring and long charge diffusion path, resulting in moderate photocatalytic activity. The bridged phenyl embedded in the CN structure was used to reduce the symmetry of the tri-s-triazine ring. In addition, the CN material was constructed with a porous and hollow sphere structure to shorten the diffusion path of charge carriers. Herein, simple thermal polymerization of a trimesic acid-doped melamine-cyanuric acid (MCA) supramolecular was employed to construct phenyl-bridged graphitic carbon nitride (Ph-CN-MCA) with a hollow sphere structure composed of porous nanosheets for visible-light catalytic H2 evolution. The porous and hollow sphere-structured Ph-CN-MCA possessed increased degree of polymerization, more negative conduction band potential, enlarged Brunauer-Emmett-Teller (BET) surface area, and shortened charge diffusion path. In addition, bridged phenyl embedded in the Ph-CN-MCA structure not only accelerated the dissociation of photogenerated carriers but also narrowed the band gap and extended the visible-light absorption. Further, the separated highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of Ph-CN-MCA facilitated the spatial dissociation of photogenerated charges, which was also confirmed by theoretical calculations. As a consequence, compared with the reference CN-MA catalyst prepared from melamine, Ph-CN-MCA showed approximately 48.42 times the photocatalytic H2 evolution under visible-light irradiation. The developed synthetic method herein highlights that phenyl-bridged graphitic carbon nitride with a porous and hollow sphere structure could provide an efficient platform to boost the dissociation of photoexcited charge carriers and photocatalytic H2 evolution.

Bone marrow mesenchymal stem cells induce M2 microglia polarization through PDGF-AA/MANF signaling.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) are capable of shifting the microglia/macrophages phenotype from M1 to M2, contributing to BMSCs-induced brain repair. However, the regulatory mechanism of BMSCs on microglia/macrophages after ischemic stroke is unclear. Recent evidence suggests that mesencephalic astrocyte-derived neurotrophic factor (MANF) and platelet-derived growth factor-AA (PDGF-AA)/MANF signaling regulate M1/M2 macrophage polarization. AIM: To investigate whether and how MANF or PDGF-AA/MANF signaling influences BMSCs-mediated M2 polarization. METHODS: We identified the secretion of MANF by BMSCs and developed transgenic BMSCs using a targeting small interfering RNA for knockdown of MANF expression. Using a rat middle cerebral artery occlusion (MCAO) model transplanted by BMSCs and BMSCs-microglia Transwell coculture system, the effect of BMSCs-induced downregulation of MANF expression on the phenotype of microglia/macrophages was tested by Western blot, quantitative reverse transcription-polymerase chain reaction, and immunofluorescence. Additionally, microglia were transfected with mimics of miR-30a*, which influenced expression of X-box binding protein (XBP) 1, a key transcription factor that synergized with activating transcription factor 6 (ATF6) to govern MANF expression. We examined the levels of miR-30a*, ATF6, XBP1, and MANF after PDGF-AA treatment in the activated microglia. RESULTS: Inhibition of MANF attenuated BMSCs-induced functional recovery and decreased M2 marker production, but increased M1 marker expression in vivo or in vitro. Furthermore, PDGF-AA treatment decreased miR-30a* expression, had no influence on the levels of ATF6, but enhanced expression of both XBP1 and MANF. CONCLUSION: BMSCs-mediated MANF paracrine signaling, in particular the PDGF-AA/miR-30a*/XBP1/MANF pathway, synergistically mediates BMSCs-induced M2 polarization.

The inhibition of the interaction between the anthrax toxin and its cellular receptor by an anti-receptor monoclonal antibody.

The high affinity binding of the anthrax protective antigen (PA) to one of its receptors, capillary morphogenesis protein 2 (CMG2), is essential for the intoxication process of anthrax toxin. To acquire novel research tools to study the PA-CMG2 interaction, we generated several anti-CMG2 monoclonal antibodies (MAbs). We demonstrated that one of the MAbs, 4B5, could inhibit PA-CMG2 binding and could also protect the sensitive cells against an anthrax lethal toxin challenge. We identified the epitope recognized by 4B5 and confirmed that the key residues of the epitope were the residues (119)YI-LK(125) of CMG2. Based on our results, we propose that 4B5 binds to the E122 pocket of CMG2 and interrupts the interaction between the pocket and the PA 2beta3-2beta4 loop. To our knowledge, this is the first report to illustrate that an anti-CMG2 antibody could inhibit the PA-CMG2 interaction and therefore interfere with the intoxication of anthrax toxin.