Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.

High temperature requirement A1 (HTRA1) is a member of the serine protease family, comprising four structural domains: IGFBP domain, Kazal domain, protease domain and PDZ domain. HTRA1 encodes a serine protease, a secreted protein that is widely expressed in the vasculature. HTRA1 regulates a wide range of physiological processes through its proteolytic activity, and is also involved in a variety of vascular abnormalities-related diseases. This article reviews the role of HTRA1 in the development of vascular abnormalities-related hereditary cerebral small vessel disease (CSVD), age-related macular degeneration (AMD), tumors and other diseases. Through relevant research advances to understand the role of HTRA1 in regulating signaling pathways or refolding, translocation, degradation of extracellular matrix (ECM) proteins, thus directly or indirectly regulating angiogenesis, vascular remodeling, and playing an important role in vascular homeostasis, further understanding the mechanism of HTRA1's role in vascular abnormality-related diseases is important for HTRA1 to be used as a therapeutic target in related diseases.

Cerebral endothelial cells mediated enhancement of brain pericyte number and migration in oxygen-glucose deprivation involves the HIF-1α/PDGF-ß signaling.

The present study focused on whether hypoxia-inducible factor-1alpha (HIF-1α) and platelet-derived factor-beta (PDGF-ß) are involved in the crosstalk between brain microvascular endothelial cells (BMECs) and brain vascular pericytes (BVPs) under ischaemic-hypoxic conditions. Mono-cultures or co-cultures of BVPs and BMECs were made for the construction of the blood-brain barrier (BBB) model in vitro and then exposed to control and oxygen-glucose deprivation (OGD) conditions. BBB injury was determined by assessing the ability, apoptosis, and migration of BVPs and the transendothelial electrical resistance and horseradish peroxidase permeation of BMECs. Relative mRNA and protein levels of HIF-1α and PDGF-ß, as well as tight junction proteins ZO-1 and claudin-5 were analyzed by western blotting, reverse transcription quantitative PCR, and/or immunofluorescence staining. Dual-luciferase reporter assays assessed the relationship between PDGF-ß and HIF-1α. Co-culturing with BMECs alleviated OGD-induced reduction in BVP viability, elevation in BVP apoptosis, and repression in BVP migration. Co-culturing with BVPs protected against OGD-induced impairment on BMEC permeability. OGD-induced HIF-1α upregulation enhanced PDGF-ß expression in mono-cultured BMECs and co-cultured BMECs with BVPs. Knockdown of HIF-1α impaired the effect of BMECs on BVPs under OGD conditions, and PDGFR-ß silencing in BVPs blocked the crosstalk between BMECs and BVPs under OGD conditions. The crosstalk between BMECs and BVPs was implicated in OGD-induced BBB injury through the HIF-1α/PDGF-ß signaling.

Redox metabolism maintains the leukemogenic capacity and drug resistance of AML cells.

Rewiring of redox metabolism has a profound impact on tumor development, but how the cellular heterogeneity of redox balance affects leukemogenesis remains unknown. To precisely characterize the dynamic change in redox metabolism in vivo, we developed a bright genetically encoded biosensor for H2O2 (named HyPerion) and tracked the redox state of leukemic cells in situ in a transgenic sensor mouse. A H2O2-low (HyPerion-low) subset of acute myeloid leukemia (AML) cells was enriched with leukemia-initiating cells, which were endowed with high colony-forming ability, potent drug resistance, endosteal rather than vascular localization, and short survival. Significantly high expression of malic enzymes, including ME1/3, accounted for nicotinamide adenine dinucleotide phosphate (NADPH) production and the subsequent low abundance of H2O2. Deletion of malic enzymes decreased the population size of leukemia-initiating cells and impaired their leukemogenic capacity and drug resistance. In summary, by establishing an in vivo redox monitoring tool at single-cell resolution, this work reveals a critical role of redox metabolism in leukemogenesis and a potential therapeutic target.

Design and establishment of a large-scale controlled ecological life-support system integrated experimental platform.

A Controlled Ecological Life-Support System (CELSS) can meet the demands of food, oxygen, and water for human, as well as providing psychological benefits during deep space exploration by the continuous materials regeneration. Many key techniques of the platform are needed to explore before applying to the extraterrestrial planets. In this study, a large-scale CELSS integrated experimental platform was designed and constructed to meet the basic life-support material demands of six crew members (max). The platform was composed of four kinds of cabins including Crew Cabin (CC), Plant Cabin (PC), Life-Support Cabin (LSC), Resource Recycling Cabin (RRC) and affiliated facilities. Eight cabins were involved in the platform, i.e., CCs I and II, PCs I, II, III and IV, LSC, and RRC. The platform involved 15 subsystems and covered a plant culture area of 206.6 m2 (a max extensible area of 260 m2) and a total volume of 1340 m3. The joint debuggings and the 4-subject 180-day CELSS integration experiment were carried out successfully. The material closures were 55% (on average) for food (70.8% in highly efficient production period), 100% for atmospheric regeneration, 100% for water regeneration, and 87.7% for recycled solid waste in the 4-subject 180-day integration experiment. It verified that the indicators of the platform meet the technical requirements and realize food regeneration, air regeneration and water regeneration through the integration of physico-chemical technique and biological technique for the long-term survivals of six crew members in the closed cabins.

Highly efficient UV/H2O2 technology for the removal of nifedipine antibiotics: Kinetics, co-existing anions and degradation pathways.

This study investigates the degradation of nifedipine (NIF) by using a novel and highly efficient ultraviolet light combined with hydrogen peroxide (UV/H2O2). The degradation rate and degradation kinetics of NIF first increased and then remained constant as the H2O2 dose increased, and the quasi-percolation threshold was an H2O2 dose of 0.378 mmol/L. An increase in the initial pH and divalent anions (SO42- and CO32-) resulted in a linear decrease of NIF (the R2 of the initial pH, SO42- and CO32- was 0.6884, 0.9939 and 0.8589, respectively). The effect of monovalent anions was complex; Cl- and NO3- had opposite effects: low Cl- or high NO3- promoted degradation, and high Cl- or low NO3- inhibited the degradation of NIF. The degradation rate and kinetics constant of NIF via UV/H2O2 were 99.94% and 1.45569 min-1, respectively, and the NIF concentration = 5 mg/L, pH = 7, the H2O2 dose = 0.52 mmol/L, T = 20 ℃ and the reaction time = 5 min. The ·OH was the primary key reactive oxygen species (ROS) and ·O2- was the secondary key ROS. There were 11 intermediate products (P345, P329, P329-2, P315, P301, P274, P271, P241, P200, P181 and P158) and 2 degradation pathways (dehydrogenation of NIF → P345 → P274 and dehydration of NIF → P329 → P315).

Occurrence of antibiotics in the Xiaoqing River basin and antibiotic source contribution-a case study of Jinan city, China.

Twenty antibiotics were investigated to evaluate the degree of antibiotic pollution, the temporal and spatial antibiotic distribution and the ecological risks in the Xiaoqing River basin (main stream). The total antibiotic concentrations in surface water and sediment were 0.99 to 832.4 ng L-1 and 9.71 to 7841.61 ng g-1, respectively, and that ofloxacin was the dominant antibiotic. However, ofloxacin, erythromycin, clarithromycin and sulfamethoxazole posed high risks to algae, among which clarithromycin presented the highest risk quotients (23.8). In addition, there were spatial and temporal differences in the antibiotic concentration distribution. Temporally, the following trend was detected: dry season > normal season > wet season; spatially, the following trend was detected: Jinan > Dongying > Binzhou > Zibo > Weifang. Meanwhile, we used the PCA-MLR model to quantify the contribution rate of the four sewage treatment plants A, B, C and D. Factor 1 (co-sources A, B, C, D) contributed 64.1% of the total antibiotic concentration in the Xiaoqing River. According to the estimated flux into the sea, approximately 972.31 kg of antibiotics were discharged into Bohai Bay in 2017, posing a potential threat to the marine ecosystem. As a comprehensive river channel used for flood control, waterlogging, irrigation and shipping, its water quality safety is of great significance to the surrounding residents and ecological safety. Therefore, further investigations of antibiotic pollution and source contribution are necessary.

The preparation of a novel iron/manganese binary oxide for the efficient removal of hexavalent chromium [Cr(vi)] from aqueous solutions.

To remove hexavalent chromium Cr(vi) efficiently, a novel Fe-Mn binary oxide adsorbent was prepared via a "two-step method" combined with a co-precipitation method and hydrothermal method. The as-prepared Fe-Mn binary oxide absorbent was characterized via transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectra (FTIR), thermogravimetric analysis (TGA), zeta potential, BET and X-ray photoelectron spectroscopy (XPS). The results indicated that the morphology of the adsorbent was rod-like with length of about 100 nm and width of about 50-60 nm, specific surface area was 63.297 m2 g-1, has the composition of α-Fe2O3, ß-MnO2 and MnFe2O4 and isoelectric point was observed at pH value of 4.81. The removal of Cr(vi) was chosen as a model reaction to evaluate the adsorption capacity of the Fe-Mn binary oxide adsorbent, indicating that the Fe-Mn binary oxide adsorbent showed high adsorption performance (removal rate = 99%) and excellent adsorption stability (removal rate > 90% after six rounds of adsorption). The adsorption behavior of the Fe-Mn binary oxide was better represented by the Freundlich model (adsorption isotherm) and the pseudo-second-order model (adsorption kinetic), suggesting that the adsorption process was multi-molecular layer chemical adsorption. The possible adsorption mechanism of the Fe-Mn binary oxide for the removal of Cr(vi) included the protonation process and the electrostatic attraction interactions.

Efficient Adsorption of Sulfamethazine onto Modified Activated Carbon: A Plausible Adsorption Mechanism.

Activated carbon (AC) was modified by FeCl3. Batch experiments were carried out to evaluate the characteristics of equilibrium, kinetics and thermodynamics of Sulfamethazine adsorption onto original and modified AC. The results showed that Fe3+ treatment changed the surface area, pore volume and surface zeta potential and increased the number of surface oxygenic functional groups. The adsorption of Sulfamethazine on modified activated carbon (MAC) was significantly improved. Isotherm test results revealed that the adsorption isotherms of Sulfamethazine on MAC fit the Freundlich, Langmuir and Temkin equations well. The maximum adsorption quantity of Sulfamethazine on MAC was 17.2414 mg/g at 25 °C. The adsorption kinetics of Sulfamethazine on AC and MAC can be characterized by the pseudo-second-order model. The adsorption process was affected by membrane diffusion, surface adsorption and internal diffusion. The adsorption quantities of Sulfamethazine first increased and then decreased for pH between 3 and 10. The removal efficiencies decreased with increasing temperature, which is favorable for adsorption at low temperature. It was also found that the mechanisms of adsorption included micropore capture and electrostatic, hydrogen bonding, π-π electron donor-acceptor (EDA) and coordination interactions as well as other interactions.

Highly-efficient photocatalytic degradation of methylene blue by PoPD-modified TiO 2 nanocomposites due to photosensitization-synergetic effect of TiO2 with PoPD.

Poly-o-phenylenediamine modified TiO2 nanocomposites were successfully synthesized via an 'in situ' oxidative polymerization method. The modified nanocomposites were characterized by BET, XRD, TEM, FT-IR, TGA, XPS, EA and UV-Vis DRS. The photocatalytic degradation of methylene blue was chosen as a model reaction to evaluate the photocatalytic activities of TiO2 and PoPD/TiO2. The results indicated that PoPD/TiO2 nanocomposites exhibited good photocatalytic activity and stability. The photocatalytic activity of PoPD/TiO2 increased as the initial pH increased because of electrostatic adsorption between the photocatalyst and MB as well as the generation of ·OH, whereas it exhibited an earlier increasing and later decreasing trend as the concentration of the photocatalyst increased owing to the absorption of visible light. The photocatalytic stability of the PoPD/TiO2 nanocomposite was dependent on the stability of its structure. Based on radical trapping experiments and ESR measurements, the origin of oxidizing ability of PoPD/TiO2 nanocomposites on photocatalytic degradation of MB was proposed, which taking into account of ·OH and ·O2- were the first and second important ROS, respectively. The possible photocatalytic mechanism and photocatalytic activity enhanced mechanism has been proposed, taking into account the photosensitization effect and synergetic effect of TiO2 with PoPD.

Highly efficient photocatalytic degradation of methylene blue by PoPD/TiO2 nanocomposite.

The poly-o-phenylenediamine (PoPD)/TiO2 nanocomposite was successfully synthesized via 'in situ' oxidative polymerization method. The modified photocatalysts were characterized by BET, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrarad spectra (FT-IR), thermogravimrtic analysis (TGA), X-ray photoelectron spectroscopy (XPS), Ultraviolet-visible diffuse reflectance spectrum (UV-Vis DRS) and Photocurrent Test. The results showed that the PoPD exists on the surface of TiO2, the presence of PoPD does not impact on the lattice structure and grain size of TiO2, and the presence of PoPD enhances the visible response and photoelectric property. The photocatalytic degradation of methylene blue (MB) was chosen as a model reaction to evaluate the photocatalytic activities of TiO2 and PoPD/TiO2. The optimal preparation condition was the molar ratio of oPD to TiO2 = 3:1, HCl concentration = 1.2 mol/L, the molar ratio of APS to oPD = 1:1. The apparent first-order rate constant kapp of PoPD/TiO2 nanocomposite was 0.0098 min-1, which is 6 times higher than TiO2 (0.0016 min-1). Meanwhile, the PoPD/TiO2 nanocomposites showed excellent photocatalytic stability, and the photocatalytic stability was depended on the stability of structure. At last, the photocatalytic mechanism of POPD/TiO2 nanocomposites was also proposed based on the synergetic effect between TiO2 and PoPD.

[Establishment and identification of A new HPV positive esophageal cancer cell line].

In order to explore the relationship between human papilloma virus ( HPV) and upper gastrointestinal cancer(esophageal cancer), An esophageal squamous cell carcinoma(ESCC) tissue was obtained from a 76 year old Chinese female patient from Anyang city, a high-incidence area for esophageal cancer, in China. Transplanted tumor was formed through direct SCID mouse tumorigenicity experiment and cultured monolayer cells were obtained after several passages and screenings Immunofluorescence test, cell growth curve, soft agar assay, chromosome analysis and tissues HE staining were also performed to confirm the epithelial cell origin. Cell DNA STR typing results showed that no three alleles was observed,indicating no contamination of human cells. DNA analysis revealed the presence of HPV type 18 DNA in this cell line. DOLINK test found the E6 protein expression of HPV virus. We concluded that the established cell line is a new esophageal squamous cell-origincarcinoma cell line with HPV DNA positive and expression of viral oncoprotein. It provides new cytologic material for performing etiology studies on the occurrence and development of esophageal cancer.

[Immune potency of recombinant adeno-associated virus combined with recombinant adenovirus vaccine containing HIV-1 gp120].

OBJECTIVE: To study the immune effect of recombinant adeno-associated virus (rAAV) combined with recombinant adenovirus (rAdV) vaccine in BALB/c mice. METHODS: The codon-modified HIV-1 gp120 gene was inserted into plasmid of adeno-associated virus and adenovirus vector separately. Then the rAAV and rAdV vaccines were constructed. BALB/c mice were immunized with rAAV and rAdV vaccines in different administration scheme. The IgG antibody was detected by ELISA and CTL response was detected by intracellular cytokine stain assay. RESULTS: Both rAAV and rAdV vaccine could express gp120 gene; the mice primed with rAAV at week 0, 2 and boosted with rAdV at week 5, 14 and 20 elicited the strongest gp120 specific CTL and IgG antibody response. CONCLUSION: The mice primed with rAAV and boosted with rAdV could elicit specific CTL response and IgG antibody.

[Construction and analysis of activity of an HIV-1/bovine immunodeficiency virus chimeric clone cDNA].

OBJECTIVE: Chimeric human/bovine immunodeficiency virus (HBIV) cDNA was constructed by replacing HIV tat and LTR with bovine immunodeficiency virus (BIV) tat and LTR to study the activity of BIV tat and LTR in the chimerae. METHODS: The target fragments of BIV tat, LTR and HIV gag, pol, env were respectively amplified by using PCR and sequentially inserted into pBluescript SK(+) vector. The chimeric clone was transfected into human MT4 cells. The transcript and gene expression of the HBIV chimeric virus were detected by using RT-PCR and a reverse transcriptase assay, respectively. RESULTS: BIV tat mRNA and HIV gag mRNA were detected. The reverse transcriptase activity of the chimeric virus was analyzed in the fluctuation curve. CONCLUSIONS: In chimeric HBIV cDNA transfected MT?4 cells, BIV tat and HIV gag were transcripted. The reverse transcriptase of the chimeric virus had biological activity. These data suggest that in MT4 cells, BIV LTR had promoter activity and BIV tat had the function of transactivation in the chimeric virus. The study of the chimeric virus with infectivity is in progress.

Construction and characterization of a chimeric virus (BIV/HIV-1) carrying the bovine immunodeficiency virus gag-pol gene.

HIV-1(HXB2) 5'LTR region, most of BIV(R29) gag-pol segment and HIV-1(HXB2) pol IN-3'LTR region were respectively amplified. A chimeric clone, designated as pHBIV(3753), was constructed by cloning three fragments sequentially into pUC18. MT4 cells were transfected with pHBIV3753. The replication and expressions of the chimeric virus (HBIV3753) were monitored by RT activity and IFA. The results firstly demonstrated that it is possible to generate a new type of the BIV/HIV-1 chimeric virus containing BIV gag-pol gene.