RAC2 promotes abnormal proliferation of quiescent cells by enhanced JUNB expression via the MAL-SRF pathway.

Radiation-induced lung injury (RILI) occurs most often in radiotherapy of lung cancer, esophageal cancer, and other thoracic cancers. The occurrence of RILI is a complex process that includes a variety of cellular and molecular interactions, which ultimately result in carcinogenesis. However, the underlying mechanism is unknown. Here we show that Ras-related C3 botulinum toxin substrate 2 (RAC2) and transcription factor jun-B (JUNB) were upregulated in non-small cell carcinoma (NSCLC) tissues and were associated with poor prognoses for NSCLC patients. Ionizing radiation also caused increased expression of RAC2 in quiescent stage cells, and the reentry of quiescent cells into a new cell cycle. The activity of the serum response factor (SRF) was activated by RAC2 and other Rho family genes (RhoA, ROCK, and LIM kinase). Consequently, JUNB acted as an oncogene and induced abnormal proliferation of quiescent cells. Together, the results showed that RAC2 can be used as a target gene for radiation protection. A better understanding of the RAC2 and JUNB mechanisms in the molecular etiology of lung cancer will be helpful in reducing cancer risks and side effects during treatment of this disorder. Our study therefore provides a new perspective on the involvement of RAC2 and JUNB as oncogenes in the tumorigenesis of NSCLC.

Epidemiology of Carbapenem-Resistant Enterobacteriaceae Infections: Report from the China CRE Network.

Carbapenem-resistant Enterobacteriaceae (CRE) infection is highly endemic in China, but estimates of the infection burden are lacking. We established the incidence of CRE infection from a multicenter study that covered 25 tertiary hospitals in 14 provinces. CRE cases defined as carbapenem-nonsusceptible Citrobacter freundii, Escherichia coli, Enterobacter cloacae, or Klebsiella pneumoniae infections during January to December 2015 were collected and reviewed from medical records. Antimicrobial susceptibility testing and carbapenemase gene identification were performed. Among 664 CRE cases, most were caused by K. pneumoniae (73.9%), followed by E. coli (16.6%) and E. cloacae (7.1%). The overall CRE infection incidence per 10,000 discharges was 4.0 and differed significantly by region, with the highest in Jiangsu (14.97) and the lowest in Qinghai (0.34). Underlying comorbidities were found in 83.8% of patients; the median patient age was 62 years (range, 45 to 74 years), and 450 (67.8%) patients were male. Lower respiratory tract infections (65.4%) were the most common, followed by urinary tract infection (16.6%), intra-abdominal infection (7.7%), and bacteremia (7.7%). The overall hospital mortality rate was 33.5%. All isolates showed nonsusceptibility to carbapenems and cephalosporins. The susceptibility rate of polymyxin B was >90%. Tigecycline demonstrated a higher susceptibility rate against E. coli than against K. pneumoniae (90.9% versus 40.2%). Of 155 clinical isolates analyzed, 89% produced carbapenemases, with a majority of isolates producing KPC (50%) or NDM (33.5%)-type beta-lactamases among K. pneumoniae and E. coli The incidence of CRE infection in China was 4.0 per 10,000 discharges. The patient-based disease burden in tertiary hospitals in China is severe, suggesting an urgent need to enhance infection control.

Construction of boundary-surface-based Chinese female astronaut computational phantom and proton dose estimation.

With the rapid development of China's space industry, the importance of radiation protection is increasingly prominent. To provide relevant dose data, we first developed the Visible Chinese Human adult Female (VCH-F) phantom, and performed further modifications to generate the VCH-F Astronaut (VCH-FA) phantom, incorporating statistical body characteristics data from the first batch of Chinese female astronauts as well as reference organ mass data from the International Commission on Radiological Protection (ICRP; both within 1% relative error). Based on cryosection images, the original phantom was constructed via Non-Uniform Rational B-Spline (NURBS) boundary surfaces to strengthen the deformability for fitting the body parameters of Chinese female astronauts. The VCH-FA phantom was voxelized at a resolution of 2 × 2 × 4 mm(3)for radioactive particle transport simulations from isotropic protons with energies of 5000-10 000 MeV in Monte Carlo N-Particle eXtended (MCNPX) code. To investigate discrepancies caused by anatomical variations and other factors, the obtained doses were compared with corresponding values from other phantoms and sex-averaged doses. Dose differences were observed among phantom calculation results, especially for effective dose with low-energy protons. Local skin thickness shifts the breast dose curve toward high energy, but has little impact on inner organs. Under a shielding layer, organ dose reduction is greater for skin than for other organs. The calculated skin dose per day closely approximates measurement data obtained in low-Earth orbit (LEO).

[Expression of TPO mimetic peptide chimeric proteins with human IgG1 Fc fragments and their biological characters].

Many antineoplastic agents can cause myelosuppression and thrombocytopenia. Thrombopoietin (TPO) is believed to be the major cytokine affecting the proliferation and maturation of megakaryocytes and increasing circulating platelet levels. We have designed and synthesized a TPO mimetic peptide, it can increase circulating platelet levels in vivo. For increasing half-life and forming dimer, the peptide was expressed as chimeric proteins with human IgG1 Fc fragments. The cDNA of TPO mimetic peptide was synthesized chemically and linked respectively to 5' terminus of human IgG1 Fc cDNA fragments in various length (Fc1: Fc 5' 648 bp; Fc2: Fc 5' 270 bp; Fc3: Fc 5' 267 bp; Fc4: Fc 5' 90 bp), and cloned into expression plasmid pET28a (+) for constructing four recombinant plasmids. By transforming the four recombinant plasmids into E. coli. BL21 (DE3) respectively, we got 3 kinds of engineered E. coli which express TPO + Fc chimeric proteins(28 kD TPO + Fc1, 12 kD TPO + Fc2 and 12 kD TPO + Fc3) at high level respectively, the expressed proteins were purified with DEAE-Sepharose FF and S-Sepharose FF column. The bioactivities of the expressed chimeric proteins(TPO + Fc1, TPO + Fc2 and TPO + Fc3), TPO mimetic peptide, and PEG4000 coupled TPO mimetic peptide were evaluated with Ba/F3-mp1 in vitro and with carboplatin-induced thrombocytopenia mice in vivo, the expressed chimeric proteins have higher activity than TPO mimetic peptide both in vitro and in vivo, the EC50 on Ba/F3-mp1 cells were 13, 10, 10, 50, and 25 nmol/L respectively, all of them can increase circulating platelet counts. Their imol/Lunogenicity were valuated in mice, none of them can elicit mice to produce antibodies to TPO mimetic peptide, meanwhile three TPO + Fc chimeric proteins can elicit mice to produce antibodies to human IgG1 Fc. These studies have laid basis for production of TPO mimetic peptide by genetic engineering.