Chitosan oligosaccharide ameliorates acute lung injury induced by blast injury through the DDAH1/ADMA pathway

<div><p>Objective</p><p>To investigate the protective effect of chitosan oligosaccharide (COS) on acute lung injury (ALI) caused by blast injury, and explore possible molecular mechanisms.</p><p>Methods</p><p>A mouse model of blast injury-induced ALI was established using a self-made explosive device. Thirty mice were randomly assigned to control, ALI and ALI + COS groups. An eight-channel physiological monitor was used to determine the mouse physiological index. Enzyme linked immunosorbent assay was used to measure serum inflammatory factors. Hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, immunofluorescence staining, real time-polymerase chain reaction and western blot assay were used to detect inflammatory reactions, oxidative stress and apoptosis.</p><p>Results</p><p>Mice were sacrificed 24 hours after successful model induction. Compared with the ALI group, the heart rate, respiration and PCO₂ were significantly lower, but the PO₂, TCO₂ and HCO₃^- were significantly higher in the ALI + COS group. Compared to ALI alone, COS treatment of ALI caused a significant decrease in the wet/dry lung weight ratio, indicating a reduction in lung edema, inflammatory cell infiltration, levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-4, IL-6 and nuclear factor kappa B mRNA and protein expression were reduced and IL-10 mRNA and protein expression was increased (<i>P</i> < 0.05). COS significantly inhibited reactive oxygen species, MDA5 and IREα mRNA and protein expressions, cell apoptosis and Bax and Caspase-3 mRNA and protein expressions, and significantly increased superoxide dismutase-1 mRNA expression, and Bcl-2 and Caspase-8 mRNA and protein expression (all <i>P</i><0.05). COS significantly increased dimethylarginine dimethylaminohydrolase 1 (DDAH1) protein expression, and reduced ADMA and p38 protein expression (<i>P</i>< 0.05).</p><p>Conclusion</p><p>Blast injury causes inflammation, oxidative stress and apoptosis in the lung tissues of mice. COS has protective effects on blast injury-induced ALI, possibly by promoting DDAH1 expression and inhibiting ADMA and mitogen-activated protein kinase pathways.</p></div

COS effects on mouse weight, heart rate, respiratory rate and blood gas analysis.

<p>The MPA2000 eight-channel physiological monitor was used to record pulmonary function. Lung function parameters were calculated by esophageal pressure, airway pressure and gas flow. After left femoral artery catheterization, connecting heart function analyzer and blood pressure sensor, mouse heart rate was continuously monitored. *<i>P</i> < 0.05, vs. control group; ^#<i>P</i> < 0.05, vs. the ALI group. COS: chitosan oligosaccharide; ALI: acute lung injury.</p

COS effects on oxidative stress in the lung.

<p>Oxidative stress in the lung was determined using immunofluorescence staining, real time-PCR and western blot. *<i>P</i> < 0.05, vs. control group; ^#<i>P</i> < 0.05, vs. ALI group. COS: chitosan oligosaccharide; ALI: acute lung injury.</p

COS effects on inflammatory factor expression in the lung.

<p>The expression of TNF-α, IL-1β, IL-4, IL-6 and IL-10 in serum were determined using ELISA kit. The expression of inflammatory factors was detected using real time-PCR and western blot. *<i>P</i> < 0.05, vs. control group; ^#<i>P</i> < 0.05, vs. ALI group. COS: chitosan oligosaccharide; ALI: acute lung injury; TNF: tumor necrosis factor; IL: interleukin.</p

COS effects on pathway protein expression in the lung.

<p>Pathway protein expression in the lung was measured using immunofluorescence staining, real time-PCR and western blot. *<i>P</i> < 0.05, vs. control group; ^#<i>P</i> < 0.05, vs. ALI group. COS: chitosan oligosaccharide; ALI: acute lung injury.</p

COS effects on the wet/dry weight ratio and pathological changes in the lung of mice.

<p>*<i>P</i> < 0.05, vs. control group; ^#P < 0.05, vs. ALI group. COS: chitosan oligosaccharide; ALI: acute lung injury.</p

Screening of the Salmonella paratyphi A CMCC 50973 strain outer membrane proteins for the identification of potential vaccine targets

National Natural Science Foundation [91029729]; Natural Science Foundation of Fujian Province [2009J01200]; key projects in the Fujian Province Science and Technology Program [2009D019]Outer membrane protein antigens usually have strong immunogenicities, closely interact with the immune system and play a significant role in the development of new vaccines. The outer membrane proteins of Salmonella paratyphi A (S. paratyphi A) were screened for immunogenicity and immunoprotection for potential vaccine targets. In this study, the bactericidal effect of antiserum against the total outer membrane proteins of S. paratyphi A CMCC 50973 strain was determined, and their immunoprotection was detected with a challenge experiment on vaccinated mice. The immunogenic outer membrane proteins were identified via immunoproteomic technology, and recombinant outer membrane proteins were expressed and purified. The immunoprotection provided by the immunogenic membrane proteins was verified through active and passive immunity challenge experiments. The result revealed a number of S. paratyphi A outer membrane proteins that were proven as strong protective antigens. Twelve immunogenic outer membrane proteins were located and identified. Five recombinant proteins (LamB, pagC, TolC, nmpC and fadL) with strong immunoprotective abilities were found via the active immunity challenge experiment, with protection rates of 95, 95, 85, 80 and 70%, respectively. They were also proven to induce good immunoprotection via the passive immunity challenge experiment, with protection rates of 65, 55, 60, 55 and 50%, respectively. The immunoprotective rate of the five-antiserum combination was 85%. In conclusion, the LamB, pagC, TolC, nmpC and fadL outer membrane proteins, with strong immunogenicities and immunoprotection, are effective protein candidate targets for the development of new vaccines, whereas the recombinant outer membrane proteins are a promising tool for improving immunoprotection

CEPC Technical Design Report -- Accelerator

International audienceThe Circular Electron Positron Collider (CEPC) is a large scientific project initiated and hosted by China, fostered through extensive collaboration with international partners. The complex comprises four accelerators: a 30 GeV Linac, a 1.1 GeV Damping Ring, a Booster capable of achieving energies up to 180 GeV, and a Collider operating at varying energy modes (Z, W, H, and ttbar). The Linac and Damping Ring are situated on the surface, while the Booster and Collider are housed in a 100 km circumference underground tunnel, strategically accommodating future expansion with provisions for a Super Proton Proton Collider (SPPC). The CEPC primarily serves as a Higgs factory. In its baseline design with synchrotron radiation (SR) power of 30 MW per beam, it can achieve a luminosity of 5e34 /cm^2/s^1, resulting in an integrated luminosity of 13 /ab for two interaction points over a decade, producing 2.6 million Higgs bosons. Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons, facilitating precise measurements of Higgs coupling at sub-percent levels, exceeding the precision expected from the HL-LHC by an order of magnitude. This Technical Design Report (TDR) follows the Preliminary Conceptual Design Report (Pre-CDR, 2015) and the Conceptual Design Report (CDR, 2018), comprehensively detailing the machine's layout and performance, physical design and analysis, technical systems design, R&D and prototyping efforts, and associated civil engineering aspects. Additionally, it includes a cost estimate and a preliminary construction timeline, establishing a framework for forthcoming engineering design phase and site selection procedures. Construction is anticipated to begin around 2027-2028, pending government approval, with an estimated duration of 8 years. The commencement of experiments could potentially initiate in the mid-2030s

CEPC Technical Design Report -- Accelerator

International audienceThe Circular Electron Positron Collider (CEPC) is a large scientific project initiated and hosted by China, fostered through extensive collaboration with international partners. The complex comprises four accelerators: a 30 GeV Linac, a 1.1 GeV Damping Ring, a Booster capable of achieving energies up to 180 GeV, and a Collider operating at varying energy modes (Z, W, H, and ttbar). The Linac and Damping Ring are situated on the surface, while the Booster and Collider are housed in a 100 km circumference underground tunnel, strategically accommodating future expansion with provisions for a Super Proton Proton Collider (SPPC). The CEPC primarily serves as a Higgs factory. In its baseline design with synchrotron radiation (SR) power of 30 MW per beam, it can achieve a luminosity of 5e34 /cm^2/s^1, resulting in an integrated luminosity of 13 /ab for two interaction points over a decade, producing 2.6 million Higgs bosons. Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons, facilitating precise measurements of Higgs coupling at sub-percent levels, exceeding the precision expected from the HL-LHC by an order of magnitude. This Technical Design Report (TDR) follows the Preliminary Conceptual Design Report (Pre-CDR, 2015) and the Conceptual Design Report (CDR, 2018), comprehensively detailing the machine's layout and performance, physical design and analysis, technical systems design, R&D and prototyping efforts, and associated civil engineering aspects. Additionally, it includes a cost estimate and a preliminary construction timeline, establishing a framework for forthcoming engineering design phase and site selection procedures. Construction is anticipated to begin around 2027-2028, pending government approval, with an estimated duration of 8 years. The commencement of experiments could potentially initiate in the mid-2030s