Activation of polyamine catabolism promotes glutamine metabolism and creates a targetable vulnerability in lung cancer.

Polyamines are a class of small polycationic alkylamines that play essential roles in both normal and cancer cell growth. Polyamine metabolism is frequently dysregulated and considered a therapeutic target in cancer. However, targeting polyamine metabolism as monotherapy often exhibits limited efficacy, and the underlying mechanisms are incompletely understood. Here we report that activation of polyamine catabolism promotes glutamine metabolism, leading to a targetable vulnerability in lung cancer. Genetic and pharmacological activation of spermidine/spermine N1-acetyltransferase 1 (SAT1), the rate-limiting enzyme of polyamine catabolism, enhances the conversion of glutamine to glutamate and subsequent glutathione (GSH) synthesis. This metabolic rewiring ameliorates oxidative stress to support lung cancer cell proliferation and survival. Simultaneous glutamine limitation and SAT1 activation result in ROS accumulation, growth inhibition, and cell death. Importantly, pharmacological inhibition of either one of glutamine transport, glutaminase, or GSH biosynthesis in combination with activation of polyamine catabolism synergistically suppresses lung cancer cell growth and xenograft tumor formation. Together, this study unveils a previously unappreciated functional interconnection between polyamine catabolism and glutamine metabolism and establishes cotargeting strategies as potential therapeutics in lung cancer.

Changes in the area of inland lakes in arid regions of central Asia during the past 30 years.

Inland lakes are major surface water resource in arid regions of Central Asia. The area changes in these lakes have been proved to be the results of regional climate changes and recent human activities. This study aimed at investigating the area variations of the nine major lakes in Central Asia over the last 30 years. Firstly, multi-temporal Landsat imagery in 1975, 1990, 1999, and 2007 were used to delineate lake extents automatically based on Normalized Difference Water Index (NDWI) threshold segmentation, then lake area variations were detailed in three decades and the mechanism of these changes was analyzed with meteorological data and hydrological data. The results indicated that the total surface areas of these nine lakes had decreased from 91,402.06 km(2) to 46,049.23 km(2) during 1975-2007, accounting for 49.62% of their original area of 1975. Tail-end lakes in flat areas had shrunk dramatically as they were induced by both climate changes and human impacts, while alpine lakes remained relatively stable due to the small precipitation variations. With different water usage of river outlets, the variations of open lakes were more flexible than those of other two types. According to comprehensive analyses, different types of inland lakes presented different trends of area changes under the background of global warming effects in Central Asia, which showed that the increased human activities had broken the balance of water cycles in this region.

[Two endmember extraction algorithms with combined spatial and spectral domain TM image].

Based on a few bands and unabundant spectral information of TM remote sensing image, two endmember extraction algorithms are put forward. First, spatial split endmember extraction algorithm, which firstly browses the image, based on the complexity of objects, divides the image into different blocks, then uses hourglass algorithm to extract endmembers. Second, region continuity algorithm, also based on dividing-into-blocks idea, which uses extraction and classification of homogenous object algorithm and spectral correlation energy level matching algorithm to extract endmembers. Finally, comparing the two algorithms, spatial split endmember extraction algorithm runs fast, with little prior knowledge, however, the probability of error extraction endmembers exists; and region continuity algorithm's precision is higher, needs for prior knowledge, and the segment process is slow. Experimental results show that both spatial-and-spectral combined endmember extraction algorithms can effectively solve the large regional scale, multispectral endmember extraction problem, and have broad application prospects.

[A remote sensing band simulation approach based on image spectral library].

The authors proposed an image spectral library based band simulation method. Firstly, the authors clustered the reference image which has the same class composition with the target image by using its pixel spectrum similarity. Secondly, the authors fetched sample from the reference image base on the former cluster image, and then built the image spectral library. Thirdly, the authors fetched the same count of each type of samples to train the simulation model. Finally, the authors simulated the target band of the target image. The experiment results show that: firstly, this method can be more precise to simulate TM blue band, and increase more than 1.2 RMSE value than that of the "Spectral Library-image" model and more than 0.6 RMSE value than that of the "image-image" model. On the other hand, our method is more stable and reliable than the "image-image" and "Spectral Library-Image" simulation model; finally, this method can be successfully applied to the blue band simulation that SPOT and MSS lacked.

Immunogenicity and safety levels of inactivated quadrivalent influenza vaccine in healthy adults via meta-analysis.

Objective: The aim of the current study was to evaluate immunogenicity and safety levels of human inactivated quadrivalent influenza vaccine (QIV) which includes two A strains (A/H1N1, A/H3N2) and two B lineages (B/Victoria, B/Yamagata) in healthy adults via meta-analysis. Methods: Searches were conducted in PubMed, Cochrane Library, ClinicalTrials.gov, and EMBASE databases published in 2011-2020 according to inclusion and exclusion criteria. The purpose was to collect and perform meta-analysis of related randomized clinical trial (RCT) data concerning safety and immunogenicity levels of human QIV compared with inactivated trivalent influenza vaccine (TIV). Results: A total of 9 literatures were included. There was no significant difference in the seroconversion(SCR) and seroprotection(SPR) between QIV and TIV for influenza A strains (A/H1N1, A/H3N2) and the B lineage included in the TIV. QIV showed superior efficacy for the B lineage not included in the TIV: SCR RR of 2.20 (95%CI: 1.44-3.37, p = .0003) and SPR RR of 1.34 (95%CI: 1.10-1.63, p = .004) for B/Victoria, and SCR RR of 1.88 (95%CI: 1.53-2.31, p < .00001) and SPR RR of 1.11 (95%CI: 1.03-1.19, p = .006) for B/Yamagata, respectively. There were no significant differences between QIV and TIV for local and systemic adverse events(AE) post-vaccination. Conclusion: In adults 18-64 years old, QIV not only produced similar immunogenicity and safety levels to TIV, but also had better immunogenicity against influenza B vaccine strains not included in TIV.

A simple and safe antibody neutralization assay based on polio pseudoviruses.

The evaluation of the immunogenicity of Sabin strain based Inactivated Poliovirus Vaccines (sIPV) necessitates the use of wild strains in neutralization assays to assess the potential cross-reactivity of antibodies. The live virus strains including wild and Sabin strains must be handled in level 3 biocontainment laboratories. To develop an alternative assay without the use of a live virus, we constructed Mahoney, MEF-1, and Saukett pseudovirions by inserting luciferase reporter genes into intact capsid proteins. Afterward, we developed a pseudovirus-based neutralization test (pNT) and evaluated for the specificity and reproducibility. We tested serum samples from a clinical trial on sIPV vaccines by pNT and compared the results with those obtained from conventional neutralization tests (cNT). A strong correlation was observed between two methods, with the correlation coefficients of all three types of IPV vaccines being greater than 0.82 (p < 0.0001). The Geometric Mean Titer (GMT) values obtained by pNT were approximately four times higher than that by cNT, revealing the better sensitivity of pNT. In conclusion, pNT is a safe, rapid and sensitive quantitative assay with the potential of being an alternative for the evaluation of the potency of polio vaccines.

Bioabsorbable Drug-Eluting Stent Versus Bare Metal Stent in Iliac Artery Evaluated by Optical Coherence Tomography: An In Vivo Study in Porcine.

OBJECTIVE: This study aimed to compare, using optical coherence tomography (OCT), the outcomes of bioabsorbable drug-eluting stent with those of bare metal stent (BMS) following implantation in porcine iliac artery. METHODS: After the placement of BMS and bioabsorbable drug-eluting stents, we used OCT and digital subtraction angiography to investigate stent appositions, arterial neointima, evagination, and restenosis at 1 and 3 months. RESULTS: At 1 and 3 months after stent implantation, OCT study was performed to investigate 32 stents and 21 788 struts. Thirty-three malapposed struts were found in the bioabsorbable drug-eluting stent groups and 2 were found in BMS groups. The average neointimal thickness, area, and in-stent stenosis were significantly lower in bioabsorbable drug-eluting stents than in BMS, while the frequency of malapposed struts was higher in the bioresorbable drug-eluting stent groups. Average neointimal thickness was lower in bioabsorbable drug-eluting stents than in BMS at 1 (0.19 ± 0.09 vs 0.67 ± 0.75 mm; P < .001) and 3 months (0.21 ± 0.08 vs 1.52 ± 0.28 mm; P < .001). CONCLUSION: Our study suggested that bioabsorbable drug-eluting stent is more effective in decreasing arterial restenosis than BMS in animal models.

Structure-Dependent Optical Properties of Self-Organized Bi2Se3 Nanostructures: From Nanocrystals to Nanoflakes.

Bismuth selenide (Bi2Se3), with a wide bulk band gap and single massless Dirac cone at the surface, is a promising three-dimensional topological insulator. Bi2Se3 possesses gapless surface states and an insulator-like bulk band gap as a new type of quantum matter. Different Bi2Se3 nanostructures were prepared using electron beam evaporation with high production efficiency. Structural investigations by energy-dispersive X-ray analysis, scanning electron microscopy, and X-ray diffraction revealed the sample stoichiometries and the structural transition mechanism from nanocrystals to nanoflakes. The optical properties systematically probed and analyzed by spectroscopic ellipsometry showed strong dependence on the nanostructures and were also predicted to have structure-modifiable technological prospects. The optical parameters, plasma frequencies, scattering rates of the free electrons, and optical band gaps were related to the topological properties of the Bi2Se3 nanostructures via light-matter interactions, offering new opportunities and approaches for studies on topological insulators and spintronics. The high-quality Bi2Se3 nanostructures provide advantages in exploring novel physics and exploiting prospective applications.

Safety and effectiveness assessment of 2011-2012 seasonal influenza vaccine produced in China: a randomized trial.

OBJECTIVE: This study evaluated the effectiveness and safety of the egg-based, trivalent, inactivated split influenza vaccine produced by the Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, China. METHODS: From March 2012 through May 2012, we enrolled a total of 1390 healthy volunteers between the ages of 3 and 80 years in a randomized clinical trial at the Hebei Disease Control Center Vaccine Clinical Evaluation Center. For all subjects, body part adverse reactions and whole-body adverse reactions were observed 30 min, 6 h, and 1-7 days' post-inoculation. If no severe adverse effects were observed 7 days' post-vaccination, the local and systemic reactions of preliminary test participants were recorded until day 28. There was no placebo group in this study. Blood samples were taken for serological testing before vaccination and 28 days' post-vaccination. RESULTS: Twenty-eight days after vaccination, the seroconversion rates of experimental and control groups were H1N1 75.3% and 75.7%, H3N2 75.8% and 71.8%, B 70.7% vs. 69.4%, (P > 0.05). The antibody Geometric Mean Titer（GMT）of experimental and control groups were H1N1 (179.7, 182.4), H3N2 (584.0, 445.7), B (201.4,191.6). The protection rate of experimental and control groups was not statistically significant (H1N1: 86% vs. 87%, H3N2: 99% vs. 98%, B: 98% vs. 98%). Also, 95% confidence intervals of the protection rate difference between the experimental and the control group were H1N1: -0.1% (-4.1,3.8) %, H3N2: 0.3% (-1.0,1.7) % and B: 0.2% (-1.5,1.9) %; confidence intervals exceeded the limit of -5%. The rates of adverse reactions between experimental and control groups were 6.3% and 7.7% in local response reactions, and 19.5% and 18.0% in systemic reactions. Three hundred and twenty-seven adverse events (AEs) in 1200 (27.76%) subjects were reported within 28 d after vaccination. No serious adverse events occurred during the study. CONCLUSIONS: The experimental vaccine three-antibody protection rate was non-inferior to the control vaccine. Our results demonstrated that the experimental vaccine achieved the primary immunogenic end point of the intended clinical protocol, as well as a secondary immunogenic end-point, with an acceptable level of safety. IRB approval for this study was issued under #2012Y0005 and registered as Clinical Trial No. NCT01551810.

Molecular characterization and antimicrobial susceptibility of tcdA-negative Clostridium difficile isolates from Guangzhou, China.

This study aimed to investigate the molecular characteristics and antimicrobial susceptibility of Clostridium difficile clinical isolates in Guangzhou, China. One hundred twenty isolates were collected from Guangzhou General Hospital at the Guangzhou Military Command in China from March 2014 to April 2015, and 9 isolates were identified as tcdA-negative/tcdB-positive (A(-)B(+)) strains. Results showed that all of the strains were confirmed to be ST37 and 0 single nucleotide variants (SNVs) were found in the PaLoc region, and >60 SNVs were identified throughout the whole genome sequence. The results show the diversity of the antibiotic and gene mutations present in these strains. All of the A(-)B(+) isolates were highly resistant to clindamycin and erythromycin; showed an average sensitivity to fluoroquinolones; and maintained a high susceptibility to metronidazole, vancomycin, and tigecycline.

Transplantation of vascular endothelial growth factor 165­transfected endothelial progenitor cells for the treatment of limb ischemia.

The present study aimed to investigate the effects of neovascularization in rabbits with limb ischemia transplanted with vascular endothelial growth factor (VEGF)165­transfected endothelial progenitor cells (EPC). Bone marrow mononuclear cells were isolated by gradient centrifugation, cultured in M199 culture medium and induced into EPCs using VEGF, basic fibroblast growth factor, and insulin­like growth factor­1, and subsequently identified. The EPCs were transfected with Adv­green fluorescent protein­VEGF165 and the proliferation potential of the cells was determined using an MTT assay. The protein expression levels of VEGF were measured by detecting its concentration levels in the supernatant using an ABC­ELISA assay. A rabbit hind limb ischemic model was established and randomly divided into three groups: (A) Control group, (B) EPC­transplanted group, and (C) Ad­VEGF165/EPCs­transplanted group. The effects of transplantation and the levels of recanalization were detected. Incorporation of the transplanted cells into the ischemic region was confirmed by 5­bromodeoxyuridine staining, and the levels of recanalization were measured by computer tomography ateriography and immunohistochemical staining. Bone marrow­derived EPCs were induced, cultivated, and successfully identified. The results of the present study determined the optimum transfection ratio that promoted the growth of EPCs. The EPCs were successfully transfected with VEGF165, and EPC proliferation was not affected by the transfection. The supernatant protein concentration levels of VEGF were markedly higher in the VEGF165­transfected group, as compared with those of the control group. Introduction of the transplanted cells into the ischemic region of group C occurred more efficiently, as compared with groups A and B. The recanalization capillary density in group C was significantly higher, as compared with groups A and B. VEGF gene transfection was able to improve the quality of EPCs, and the response of rabbits with limb ischemia to transplantation with VEGF­transfected EPCs was significantly better, as compared with transplantation with EPCs alone.