MoS2 Hollow Multishelled Nanospheres Doped Fe Single Atoms Capable of Fast Phase Transformation for Fast-charging Na-ion Batteries.

Low Na+ and electron diffusion kinetics severely restrain the rate capability of MoS2 as anode for sodium-ion batteries (SIBs). Slow phase transitions between 2H and 1T, and from NaxMoS2 to Mo and Na2S as well as the volume change during cycling, induce a poor cycling stability. Herein, an original Fe single atom doped MoS2 hollow multishelled structure (HoMS) is designed for the first time to address the above challenges. The Fe single atom in MoS2 promotes the electron transfer, companying with shortened charge diffusion path from unique HoMS, thereby achieving excellent rate capability. The strong adsorption with Na+ and self-catalysis of Fe single atom facilitates the reversible conversion between 2H and 1T, and from NaxMoS2 to Mo and Na2S. Moreover, the buffering effect of HoMS on volume change during cycling improves the cyclic stability. Consequently, the Fe single atom doped MoS2 quadruple-shelled sphere exhibits a high specific capacity of 213.3 mAh g-1 at an ultrahigh current density of 30 A g-1, which is superior to previously-reported results. Even at 5 A g-1, 259.4 mAh g-1 (83.68 %) was reserved after 500 cycles. Such elaborate catalytic site decorated HoMS is also promising to realize other "fast-charging" high-energy-density rechargeable batteries.

Urban particulate air pollution linked to dyslipidemia by modification innate immune cells.

Air particulate matter (PM) is an essential risk factor for lipid metabolism disorders. However, the underlying mechanism remains unclear. In this cross-sectional study, 216 healthcare workers were recruited to estimate the associations among the daily exposure dose (DED) of air PM, innate immune cells, and plasma lipid levels. All participants were divided into two groups according to the air particulate combined DED (DED-PMC). The peripheral white blood cell counts, lymphocyte counts, and monocyte counts and percentages were higher in the higher-exposure group (HEG) than in the lower-exposure group (LEG), whereas the percentage of natural-killer cells was lower in the HEG than in the LEG. The plasma concentrations of the total cholesterol, triglycerides, LDL-C, and apolipoprotein B were higher in the HEG than in the LEG, whereas the HDL-C and apolipoprotein A1 were lower in the HEG than in the LEG. A dose-effect analysis indicated that when the DED of the air PM increased, there were increased peripheral monocyte counts and percentages, a decreased NK cell percentage, elevated plasma concentrations of total cholesterol, triglycerides, LDL-C, and apolipoprotein B, and reduced plasma levels of HDL-C and apolipoprotein A1. In addition, the modification of the innate immune cells was accompanied by alterations in the plasma lipid levels in a dose-dependent manner. Mediation effect analysis suggested innate immune cells were the potential mediators for the associations among air PM exposure on abnormal lipid metabolism. These results indicated that chronic exposure to air PM may disturb lipid metabolism by altering the distribution of innate immune cells in the peripheral blood, ultimately advancing cardiovascular disease risk.

Reversible Transformation and Distribution Determination of Diverse Pt Single-Atom Species.

In single-atom catalysts (SACs), the complexity of the support anchoring sites creates a vast diversity of single-atom species with varied coordination environments. To date, the quantitative distribution of these diverse single-atom species in a given SAC has remained elusive. Recently, CeO2-supported metal SACs have been extensively studied by modulating their local environments via numerous synthetic strategies. However, owing to the absence of a quantitative description, unraveling the site-specific reactivity and regulating their transformation remain challenging. Here, we show that two distinct Pt/CeO2 SACs can be reversibly generated by oxidative and nonoxidative dispersions, which contain varied Pt1On-Ceδ+ single-atom species despite similar Pt charge states and coordination numbers. By means of Raman spectroscopy and computational studies, we semiquantitatively reveal the distribution of diverse Pt1On-Ceδ+ species in each specific SACs. Remarkably, the minority species of Pt1O4-Ce3+-Ov accounting for only 14.2% affords the highest site-specific reactivity for low-temperature CO oxidation among the other abundant counterparts, i.e., Pt1O4-Ce4+ and Pt1O6-Ce4+. The second nearest oxygen vacancy (Ov) not only acts synergistically with the nearby active metal sites to lower the reaction barrier but also facilitates the dynamic transformation from six-coordinated to four-coordinated sites during cyclic nonoxidative and oxidative dispersions. This work elucidates the quantitative distribution and dynamic transformation of varied single-atom species in a given SAC, offering a more intrinsic descriptor and quantitative measure to depict the inhomogeneity of SACs.

Increased body mass index linked to decreased neutralizing antibody titers of inactivated SARS-CoV-2 vaccine in healthcare workers.

Objective: Obesity is an important risk factor for COVID-19. However, whether obesity affects SARS-CoV-2 antibody production is unclear. This study aimed to identify the influence of obesity on neutralizing antibody production of an inactivated SARS-CoV-2 vaccine to better guide vaccination strategies. Methods: This cross-sectional study recruited a total of 239 healthcare workers (age, 21-50 years) from Suining Central Hospital during 22-23 April 2021. An electronic questionnaire on basic characteristics was completed by all participants. A general physical exam and fasting blood sampling by venipuncture were performed. Peripheral leukocyte counts and the ratios of leukocyte subsets, hepatorenal function, and the neutralizing antibody titers against SARS-CoV-2 were measured. Results: Among 239 healthcare workers, the participants with underweight, normal weight, overweight, and obesity accounted for 10.88%, 64.44%, 23.01%, and 1.67%, respectively. The highest peripheral monocyte counts were observed in the group with obesity, whereas the lowest were observed in the group with normal weight. Similar results were obtained with respect to percentage of peripheral monocytes. Participants with obesity had higher peripheral eosinophil counts and percentages than the other three groups. The median neutralizing antibody titer was 12.70 AU/mL, with 85.36% (n = 204) of participants were sufficiently protected against SARS-CoV-2. The lowest neutralizing antibody titers were observed in the group with obesity, whereas the highest were observed in the group that was underweight. Additionally, high BMI was significantly associated with high peripheral monocyte counts [B (95% CI) = 0.008 (0.002, 0.013)] and low neutralizing antibody titers [B (95% CI) = -1.934 (-3.663, -0.206)]. Conclusions: Obesity could induce chronic inflammation, and associated with lower neutralizing antibody titers against SARS-CoV-2 after inactivated SARS-CoV-2 vaccination.

Associations between air pollutants and risk of respiratory infection: patient-based bacterial culture in sputum.

Air pollution is a crucial risk factor for respiratory infection. However, the relationships between air pollution and respiratory infection based on pathogen detection are scarcely explored in the available literature. We detected respiratory infections through patient-based bacterial culture in sputum, obtained hourly data of all six pollutants (PM2.5, PM10, SO2, NO, CO, and O3) from four air quality monitoring stations, and assessed the relationships of air pollutants and respiratory bacterial infection and multi-drug-resistant bacteria. Air pollution remains a challenge for Mianyang, China, especially PM2.5 and PM10, and there are seasonal differences; pollution is the heaviest in winter and the lowest in summer. A total of 4237 pathogenic bacteria were detected, and the positive rate of multi-drug-resistant bacteria was 0.38%. Similar seasonal differences were found with respect to respiratory infection. In a single-pollutant model, all pollutants were significantly associated with respiratory bacterial infection, but only O3 was significantly associated with multi-drug-resistant bacteria. In multi-pollutant models (adjusted for one pollutant), the relationships of air pollutants with respiratory bacterial infection remained significant, while PM2.5, PM10, and O3 were significantly associated with the risk of infection with multi-drug-resistant bacteria. When adjusted for other five pollutants, only O3 was significantly associated with respiratory bacterial infection and the risk of infection with multi-drug-resistant bacteria, showing that O3 is an independent risk factor for respiratory bacterial infection and infection with multi-drug-resistant bacteria. In summary, this study highlights the adverse effects of air pollution on respiratory infection and the risk of infection with multi-drug-resistant bacteria, which may provide a basis for the formulation of environmental policy to prevent respiratory infections.

The associations between air pollutant exposure and neutralizing antibody titers of an inactivated SARS-CoV-2 vaccine.

Air pollution is a critical risk factor for the prevalence of COVID-19. However, few studies have focused on whether air pollution affects the efficacy of the SARS-CoV-2 vaccine. To better guide the knowledge surrounding this vaccination, we conducted a cross-section study to identify the relationships between air pollutant exposure and plasma neutralizing antibody (NAb) titers of an inactivated SARS-CoV-2 vaccine (Vero cell, CoronaVac, SINOVΛC, China). We recruited 239 healthcare workers aged 21-50 years who worked at Suining Central Hospital. Of these, 207 were included in this study, depending on vaccination date. The data regarding air pollutants were collected to calculate individual daily exposure dose (DED). The geometric mean of all six pollutant DEDs was applied to estimate the combined toxic effects (DEDcomplex). Then, the participants were divided into two groups based on the mean value of DEDcomplex. The median plasma NAb titer was 12.81 AU/mL, with 85.99% vaccine efficacy in healthcare workers against SARS-CoV-2. In exposure group, observations included lower plasma NAb titers (median: 11.13 AU/mL vs. 14.56 AU/mL), more peripheral counts of white blood cells and monocytes (mean: 6.71 × 109/L vs. 6.29 × 109/L and 0.49 × 109/L vs. 0.40 × 109/L, respectively), and a higher peripheral monocyte ratio (7.38% vs. 6.50%) as compared to the reference group. In addition, elevated air pollutant DEDs were associated with decreased plasma NAb titers. To our knowledge, this study is the first to report the relationship between air pollutant exposure and plasma NAb titers of the SARS-CoV-2 vaccine. This suggests that long-term exposure to air pollutants may inhibit plasma NAb expression by inducing chronic inflammation. Therefore, to achieve early herd immunity and hopefully curb the COVID-19 epidemic, vaccinations should be administered promptly to those eligible, and environmental factors should be considered as well.

Particulate air pollution and respiratory Haemophilus influenzae infection in Mianyang, southwest China.

Particulate air pollution is correlated with many respiratory diseases. However, few studies have focused on the relationship between air particulate exposure and respiratory Heamophilus influenzae infection. Therefore, we detected respiratory Heamophilus influenzae infection by bacterial culture of sputum of patients, and we collected particulate air pollution data (including PM2.5 and PM10) from a national real-time urban air quality platform to analyze the relationship between particulate air pollution and respiratory Heamophilus influenzae infection. The mean concentrations of PM2.5 and PM10 were 37.58 µg/m3 and 58.44 µg/m3, respectively, showing particulate air pollution remains a severe issue in Mianyang. A total of 828 strains of Heamophilus influenzae were detected in sputum by bacterial culture. Multiple correspondence analysis suggested the heaviest particulate air pollution and the highest Heamophilus influenzae infection rates were all in winter, while the lowest particulate air pollution and the lowest Heamophilus influenzae infection rates were all in summer. In a single-pollutant model, each elevation of 10 µg/m3 of PM2.5, PM10, and PM2.5/10 (combined exposure level) increased the risk of respiratory Heamophilus influenzae infection by 34%, 23%, and 29%, respectively. Additionally, in the multiple-pollutant model, only PM2.5 was significantly associated with respiratory Heamophilus influenzae infection (B, 0.46; 95% confidence interval, 0.05-0.87), showing PM2.5 is an independent risk factor for respiratory Heamophilus influenzae infection. In summary, this study highlights air particulate exposure could increase the risk of respiratory Heamophilus influenzae infection, implying that stronger measures need to be taken to protect against respiratory infection induced by particulate air pollution.

Relations of blood lead levels to echocardiographic left ventricular structure and function in preschool children.

Lead (Pb) has been proved to exert adverse effect on human cardiovascular system. However, the cardiotoxicity of Pb on children is still unclear. The aim of this study was to evaluate left ventricular (LV) structure and function, by using echocardiographic indices, in order to elucidate the effect of Pb on low-grade inflammation related to left ventricle in healthy preschool children. We recruited a total of 486 preschool children, 310 from Guiyu (e-waste-exposed area) and 176 from Haojiang (reference area). Blood Pb levels, complete blood counts, and LV parameters were evaluated. Associations between blood Pb levels and LV parameters and peripheral leukocyte counts were analyzed using linear regression models. The median blood level of Pb and the counts of white blood cells (WBCs), monocytes, and neutrophils were higher in exposed group. In addition, the exposed group showed smaller left ventricle (including interventricular septum, LV posterior wall, and LV mass index) and impaired LV systolic function (including LV fractional shortening and LV ejection fraction) regardless gender. After adjustment for confounding factors, elevated blood Pb levels were significantly associated with higher counts of WBCs and neutrophils, and lower levels of LV parameters. Furthermore, counts of WBCs, monocytes, and neutrophils were negatively correlated with LV parameters. Taken together, smaller left ventricle and impaired systolic function were found in e-waste-exposed children and associated with chronic low-grade inflammation and elevated blood Pb levels. It indicates that the heart health of e-waste-exposed children is at risk due to the long-term environmental chemical insults.

Oral antimicrobial activity weakened in children with electronic waste lead exposure.

Environmental lead (Pb) exposure can induce dysbacteriosis, impair oral health, and is associated with the development of dental caries. However, the mechanism is unclear. The aim of this study was to explore the effects of Pb toxicity on oral antimicrobial activity in children in an e-waste area. Results showed higher blood Pb levels in e-waste-exposed group children, accompanied by decreased saliva SAG (salivary agglutinin) concentrations, increased peripheral WBC (white blood cell) counts and monocyte counts, and elevated peripheral monocyte percentage. LnPb (natural logarithmic transformation of blood Pb level) was negatively correlated with saliva SAG concentration, while positively correlated with peripheral monocyte percentage. Saliva SAG concentration played a complete mediating role in the correlation of LnPb to peripheral monocyte percentage. To our knowledge, this is the first study on the relationship of environmental Pb exposure and oral antimicrobial activity in children, showing that environmental Pb exposure may weaken oral antimicrobial activity through reducing saliva SAG concentration, which may raise the risk of oral dysbacteriosis and ultimately pathogen infection.

Combined toxicity of outdoor air pollution on kidney function among adult women in Mianyang City, southwest China.

Environmental pollution is a risk factor for kidney dysfunction. However, the combined toxicity of air pollutants on kidney function is scarce. We estimated the relationship between combined toxicity of air pollutants and kidney function among adult women (n = 7071, 18-65 years old) in Mianyang City, Southwest China. We measured serum concentrations of uric acid, urea, creatinine, and cystatin C, and we calculated the individual estimated glomerular filtration rate (eGFR) using a cystatin C-based equation developed specifically for Chinese patients with CKD equation. Air pollution data were collected to calculate the individual average daily dose (ADD) of pollutants based on the air quality complex index (AQCI). Mean AQCI was higher in winter and lower in summer, and followed the monthly and seasonal trends of air pollutants. Concomitantly, individual ADD was also higher in winter and lower in summer, and the seasonal differences were reflected in the levels of kidney biomarkers (including uric acid, urea, creatinine, cystatin C, and eGFR). With an interquartile range (IQR: 1.04-1.50 m3/day/kg) increases of ADD, the serum concentrations of uric acid, urea, creatinine, and cystatin C increase [B (95%CI): 1.774 (0.318, 3.231) umol/L, 0.218 (0.1888, 0.247) mmol/L, 1.501 (1.016, 1.986) umol/L, and 0.006 (0.003, 0.009) mg/L, respectively], whereas eGFR decreases [B (95%CI): -0.776 (-1.106, -0.446) mL/min/1.73 m2]. Totally, the relationship between combined toxicity of air pollutants and kidney function in Chinese adult women suggests that the toxicity of combined air pollutants inversely affects kidney function, which might accelerate the risk of CKD.

Elevated levels of lead exposure and impact on the anti-inflammatory ability of oral sialic acids among preschool children in e-waste areas.

The oral health of preschool children in an electronic waste (e-waste) area is susceptible to lead (Pb) exposure increasing the risk of dental caries and causing periodontitis and other oral diseases. The aim of the present study is to investigate the relationship between chronic exposure to Pb and oral anti-inflammatory potential of preschool children. For this analysis, 574 preschool children from 2.5 to 6 years of age were recruited between November and December 2017, in which 357 preschool children were from Guiyu (n = 357), an e-waste-contaminated town, and 217 from Haojiang Shantou. We measured the levels of child blood Pb, salivary sialic acid, serum interleukin-6 (IL-6) and serum tumor necrosis factor-α (TNF-α), and investigated the prevalence of dental caries in deciduous teeth. The medians of blood Pb levels, serum IL-6 and TNF-α were significantly higher in the Guiyu children than in Haojiang children. Concomitantly, salivary sialic acids were lower in the Guiyu children [9.58 (3.97, 18.42) mg/dL] than in Haojiang [17.57 (5.95, 24.23) mg/dL]. Additionally, the prevalence of dental caries in deciduous teeth was significantly higher in the Guiyu children than in Haojiang (62.5% vs. 53.9%). Blood Pb levels were negatively correlated with salivary sialic acids, in which IL-6 played as a mediator of the association between blood Pb levels and saliva sialic acid concentrations according to the mediation model. To our knowledge, this is the first report on the potential association between chronic Pb exposure and the anti-inflammatory ability of oral sialic acids among preschool children. These results suggest that the chronic Pb exposure can reduce salivary sialic acid levels, attenuate oral anti-inflammatory potential and increase the potential risk of dental caries in deciduous teeth among preschool children in an e-waste site.

Assessing Global Ionosphere TEC Maps with Satellite Altimetry and Ionospheric Radio Occultation Observations.

As global navigation satellite system (GNSS)stations are sparsely distributed in oceanic area, oceanic areas usually have lower precision than continental areas on a global ionosphere maps (GIM). On the other hand, space-borne observations like satellite altimetry (SA) and ionospheric radio occultation (IRO) have substantial dual-frequency observations in oceanic areas, which could be used for total electron content (TEC) retrieval. In this paper, the Jason-2 SA and Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) IRO products were used to assess the precision of IGS GIM products. Both the systematic biases and scaling factors between the international GNSS service (IGS) GIM TEC and space-borne TEC were calculated, and the statistical results show that the biases and the scaling factors obviously vary under different temporal-spatial conditions. This analysis shows that these differences are variable with diurnal and latitude factors, that is, the differences in biases during the day time are higher than those during the night time, and larger biases are experienced at lower latitude areas than at high latitude areas. The results also show that in the southern hemisphere middle-high latitude area and some other central oceanic areas, the space-borne TEC values are even higher than GIM TEC values. As the precision of space-borne TEC should be evenly distributed around different areas on Earth, it can be explain that the TEC in these areas is undervalued by the current GIM model, and the space-borne SA and IRO techniques could be used as complementary observations to improve the accuracy and reliability of TEC values in these areas.

The association of PM2.5 with airway innate antimicrobial activities of salivary agglutinin and surfactant protein D.

Fine particulate matter ≤2.5 µm (PM2.5) is a prominent global public health risk factor that can cause respiratory infection by downregulating the amounts of antimicrobial proteins and peptides (AMPs). Both salivary agglutinin (SAG) and surfactant protein D (SPD) are important AMPs in respiratory mucosal fluid, providing protection against airway pathogen invasion and infection by inducing microbial aggregation and enhancing pathogen clearance. However, the relationship between PM2.5 and these AMPs is unclear. To better understand the relationship between PM2.5 and airway innate immune defenses, we review the respiratory antimicrobial activities of SAG and SPD, as well as the adverse effects of PM2.5 on airway innate antimicrobial defense. We speculate there exists a dual effect between PM2.5 and respiratory antimicrobial activity, which means that PM2.5 suppresses respiratory antimicrobial activity through downregulating airway AMPs, while airway AMPs accelerate PM2.5 clearance by inducing PM2.5 microbial aggregation. We propose further research on the relationship between PM2.5 and these AMPs.

Evaluation of the GPS Precise Orbit and Clock Corrections from MADOCA Real-Time Products.

The Japanese Quasi-Zenith Satellite System (QZSS) is a regional navigation satellite system covering the entire Asia-Oceania region. Except for the standard satellite navigation signals, QZSS satellites also broadcast L6E augmentation signals with real time GNSS precise orbit every 30 s and clock messages every 1 s, which is very important and necessary for Real-Time precise point positioning (RTPPP) applications. In this paper, the MADOCA real-time services derived from L6E augmentation signals were evaluated for both accuracy and availability compared with IGS final products. To avoid the datum difference of GPS orbit between MADOCA real-time and IGS final products, the 7-parameters Helmert transformation was firstly used in this paper, and then the orbit was evaluated on radial, along, and cross-track directions. On the clock evaluation, the mean satellites clock errors were taken as reference clock error, and then the standard deviation (STD) was calculated for each satellite. Furthermore, the signal in space range errors (SISRE) were also summarized to evaluate the ranging-measurement accuracy. Seven-day evaluation results show that satellite orbit, clock errors, and the final SISRE errors range as being 1.8-3.9 cm, 0.04-0.15 ns (1.2-4.5 cm), and 5-10 cm, respectively. For the one-year long-term evaluation, daily SISRE errors in 2018 show consistent performance with that of seven days. Furthermore, the open source software RTKLIB was used to evaluate the kinematic PPP performance based on the MADOCA real-time products, and it shows that the daily positioning accuracy of the 20 globally distributed IGS stations can reach 4.9, 4.2, 11.7, and 12.1 cm in the east, north, up, and 3D directions, respectively. Hence, it is concluded that the current MADOCA real-time ephemeris products can provide orbit and clock products with SISRE on centimeters level with high interval, which could meet the demands of the RTPPP solution and serve real-time users who can access the MADOCA real-time products via L6E signal or internet.

Ambient fine particulate matter inhibits innate airway antimicrobial activity in preschool children in e-waste areas.

Ambient fine particulate matter (PM2.5) is a risk factor for respiratory diseases. Previous studies suggest that PM2.5 exposure may down-regulate airway antimicrobial proteins and peptides (AMPs), thereby accelerating airway pathogen infection. However, epidemiological research is scarce. Hence, we estimated the associations between individual PM2.5 chronic daily intake (CDI) and the levels of the airway AMP salivary agglutinin (SAG), as well as peripheral leukocyte counts and pro-inflammatory cytokines, of preschool children in Guiyu (an e-waste area) and Haojiang (a reference area located 31.6 km to the east of Guiyu). We recruited 581 preschool children from Guiyu and Haojiang, of which 222 were included in this study for a matching design (Guiyu: n = 110 vs. Haojiang: n = 112). Air PM2.5 pollution data was collected to calculate individual PM2.5 CDI. The mean concentration of PM2.5 in Guiyu was higher than in Haojiang, resulting in a higher individual PM2.5 CDI. Concomitantly, saliva SAG levels were lower in Guiyu children (5.05 ng/mL) than in Haojiang children (8.68 ng/mL), and were negatively correlated with CDI. Additionally, peripheral counts of white blood cells, and the concentrations of interleukin-8 and tumor necrosis factor-alpha, in Guiyu children were greater than in Haojiang children, and were positively associated with CDI. Similar results were found for neutrophils and monocytes. To our knowledge, this is the first study on the relationship between PM2.5 exposure and innate airway antimicrobial activity in children, in an e-waste area, showing that PM2.5 pollution may weaken airway antimicrobial activity by down-regulation of saliva SAG levels, which might accelerate airway pathogen infection in children.

Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017).

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.

Upregulation of SIRT1 inhibits H2O2­induced osteoblast apoptosis via FoxO1/ß­catenin pathway.

Osteoporosis is a disease that significantly influences life expectancy and quality in humans. Oxidative stress may stimulate bone marrow osteoclast differentiation and inhibit osteoblast (OB) differentiation. OB proliferation and differentiation are affected by the forkhead box O (FoxO)1/ß­catenin signaling pathway. The osteogenic differentiation of mesenchymal stem cells (MSCs) may be promoted by silent information regulator type­1 [sirtuin (SIRT)1]. However, the molecular mechanism of SIRT1 regulation of osteogenic differentiation of MSCs remains unclear, and further elucidation is needed. The present study investigated the role of SIRT1 in the FoxO1/ß­catenin signaling pathway in oxidative stress and its mechanism in the osteoblastic progenitor cell line (MC3T3­E1). The results demonstrated that OB apoptosis and elevated oxidative stress in cells were simulated by H2O2, which was inhibited by moderate SIRT1 overexpression through reducing the oxidative stress. Further studies revealed that FOXO1 and ß­catenin pathway activity was downregulated by SIRT1 and eventually resulted in inhibition of target genes, including the proapoptotic gene B cell lymphoma­2 interacting mediator of cell death, DNA repair gene growth arrest and DNA damage inducible protein 45 and the OB differentiation suppressor gene peroxisome proliferator activated receptor (PPAR)­Î³. Furthermore, ß­catenin and PPAR­Î³ were inhibited by SIRT1. Overall, the results of the present study suggest that moderate overexpression of SIRT1 (~3­fold of normal level) may directly or indirectly inhibit apoptosis of OBs via the FOXO1 and ß­catenin signaling pathway.

Crystal Structure of an Invasivity-Associated Domain of SdrE in S. aureus.

The surface protein SdrE, a microbial surface components recognizing adhesive matrix molecule (MSCRAMM) family protein expressed on the surface of Staphylococcus aureus (S. aureus), can recognize human complement regulator Factor H and C4BP, thus making it a potentially promising vaccine candidate. In this study, SdrE278-591 was found to directly affect S. aureus host cell invasion. Additionally, the crystal structure of SdrE278-591 at a resolution of 1.25 Å was established, with the three-dimensional structure revealing N2-N3 domains which fold in a manner similar to an IgG fold. Furthermore, a putative ligand binding site located at a conserved charged groove formed by the interface between N2 and N3 domains was identified, with ß2 suspected to occupy the ligand recognizing site and undergo a structural rearrangement to allow ligand binding. Overall, these findings have further contributed to the understanding of SdrE as a key factor for S. aureus invasivity and will enable a better understanding of bacterial infection processes.

Soluble expression, purification, and characterization of active recombinant human tissue plasminogen activator by auto-induction in E. coli.

BACKGROUND: Human tissue plasminogen activator (tPA) belongs to the serine protease family. It converts plasminogen into plasmin and is used clinically to treat thrombosis. Human tPA is composed of 527 amino acids residues and contains 17 disulfide bonds. Escherichia coli has been used only rarely for the efficient production of recombinant tPA. However, the functional expression of full-length tPA that contains multiple disulfide bonds on an industrial scale remains challenging. Here, we describe the soluble expression and characterization of full-length tPA by auto-induction in E. coli. RESULTS: We achieved optimal levels of gene expression, minimized negative effects related to the production of heterologous proteins, and optimized cytoplasmic yields. Three different E. coli strains, BL21 (DE3), Rosetta, and Origami 2, could express tPA using an auto-induction mechanism. In addition, similar yields of recombinant protein were produced at temperatures of 33, 35, and 37°C. The E. coli strain origami 2 could increase disulfide bond formation in cytoplasmic tPA and produce purified soluble recombinant protein (~0.9 mg/l medium). The full-length tPA was monomeric in solution, and fibrin plate assays confirmed that the recombinant tPA displayed serine protease activity. CONCLUSIONS: This is the first report that describes the heterologous expression of correctly folded active full-length tPA. This could provide valuable information for using prokaryotic auto-induction expression systems to produce tPA at industrial and pharmaceutical levels without in vitro refolding during the production step.