Clinical Study on the Prevention of Oxaliplatin-Induced Neurotoxicity with Guilongtongluofang: Results of a Randomized, Double-Blind, Placebo-Controlled Trial

Objective. Oxaliplatin-induced peripheral neurotoxicity continues to be a kind of frequent dose-limiting toxicity for many cancer patients. This study evaluated the preventive effects of Guilongtongluofang on peripheral neurotoxicity induced by oxaliplatin in patients with colorectal tumor. Patients and Methods. From May 2007 to May 2011, we conducted a randomized, double-blind, placebo-controlled trial. 120 patients of colorectal cancer treated with adjuvant oxaliplatin-based chemotherapy were randomly enrolled into the trial group and the control group. The trial group received Guilongtongluofang (at a dose of 200 mL once a day) from 3 days prior to chemotherapy. The control group received a placebo from 3 days prior to chemotherapy. Every 2-week cycle, neurotoxicity was evaluated using numeric rating scale for pain intensity and experienced relief. The primary endpoint was efficacy measurement which included oxaliplatin-induced neurotoxicity and tumor response. The differences of side effects between the two groups were also analyzed. Results. The percentage of grades 1-2 neurotoxicity was significantly lower in the trial group than that in the control group (13.3% versus 20.0%; P0.05). Conclusion. This study provides evidence that Guilongtongluofang is a promising drug for the prevention of oxaliplatin-induced neurotoxicity in patients with colorectal cancer, and it does not reduce the efficacy of oxaliplatin

Analysis of gene expression in Kalanchoe daigremontiana leaves during plantlet formation under drought stress

Background: Kalanchoe daigremontiana is an attractive model system for the study of the molecular mechanisms of somatic embryogenesis and organogenesis competence due to its formation of plantlets with adventitious roots on the leaf margins that are derived from somatic embryos. The suppression subtractive hybridization technique was used to investigate gene expression during asexual reproduction. Leaves from plants subjected to drought stress provided the source of \u2018Tester\u2019 DNA, and leaves from plants grown under normal conditions provided the \u2018Driver\u2019 DNA for subtractive hybridization. Results: A total of 481 high quality ESTs were generated, which clustered into 390 unigenes. Of these unigenes, 132 grouped into 12 functional categories, suggesting that asexual reproduction is a complicated process involving a large number of genes. The expression characteristics of selected genes from the SSH library were determined by real-time PCR and were classified into five groups, suggesting that gene expression patterns during asexual reproduction are complex. Up-regulation of S-adenosylhomocysteine hydrolase suggested that a decrease in cytokinin levels promotes the initiation of plantlet formation. Many other genes, such as inorganic pyrophosphatase and glutamate decarboxylase, play important roles in gene regulation during asexual reproduction. Conclusion: Our results provide a framework and unified platform on which future research on asexual reproduction in K. daigremontiana can be based. This represents the first genome-wide study of asexual reproduction in K. daigremontiana

Detection and Genomic Characterization of a Morganella morganii Isolate From China That Produces NDM-5

The increasing prevalence and transmission of the carbapenem resistance gene blaNDM–5 has led to a severe threat to public health. So far, blaNDM–5 has been widely detected in various species of Enterobacterales and different hosts across various cities. However, there is no report on the blaNDM–5– harboring Morganella morganii. In January 2016, the first NDM-5-producing Morganella morganii L241 was found in a stool sample of a patient diagnosed as recurrence of liver cancer in China. Identification of the species was performed using 16S rRNA gene sequencing. Carbapenemase genes were identified through both PCR and sequencing. To investigate the characteristics and complete genome sequence of the blaNDM–5-harboring clinical isolate, antimicrobial susceptibility testing, S1 nuclease pulsed field gel electrophoresis, Southern blotting, transconjugation experiment, complete genome sequencing, and comparative genomic analysis were performed. M. morganii L241 was found to be resistant to broad-spectrum cephalosporins and carbapenems. The complete genome of L241 is made up from both a 3,850,444 bp circular chromosome and a 46,161 bp self-transmissible IncX3 plasmid encoding blaNDM–5, which shared a conserved genetic context of blaNDM–5 (ΔIS3000-ΔISAba125-IS5-blaNDM–5-ble-trpF-dsbC-IS26). BLASTn analysis showed that IncX3 plasmids harboring blaNDM genes have been found in 15 species among Enterobacterales from 13 different countries around the world thus far. In addition, comparative genomic analysis showed that M. morganii L241 exhibits a close relationship to M. morganii subsp. morganii KT with 107 SNPs. Our research demonstrated that IncX3 is a key element in the worldwide dissemination of blaNDM-5 among various species. Further research will be necessary to control and prevent the spread of such plasmids

Analysis of Optimal Injection Ratio of Vapor Injection Heat Pump for Electric Railway Vehicles

Air-source heat pump with vapour injection is a prospective efficient heating method for electric railway vehicles in cold regions. A heating performance analysis modelling for air source heat pump with vapour injection is set up for performance optimization in this paper. The maximum errors of the program are within 15%. Heating performance, as well as the optimal injection ratio is analysed. The optimal injection ratio varies mainly from 0.12 to 0.3 under the typical working condition of railway vehicles in winter. It goes up with increasing inlet air temperature of condenser and goes down with increasing ambient temperature. The ambient temperature has very little effect on the optimal injection temperature of the internal heat exchanger. The results indicate that the expander valve opening of the injection branch can be controlled by its outlet temperature to get the optimal heating performance

Small RNA zippers lock miRNA molecules and block miRNA function in mammalian cells.

MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed \u27small RNA zipper\u27. It is designed to connect miRNA molecules end to end, forming a DNA-RNA duplex through a complementary interaction with high affinity, high specificity and high stability. Two miRNAs, miR-221 and miR-17, are tested in human breast cancer cell lines, demonstrating the 70∼90% knockdown of miRNA levels by 30-50 nM small RNA zippers. The miR-221 zipper shows capability in rescuing the expression of target genes of miR-221 and reversing the oncogenic function of miR-221 in breast cancer cells. In addition, we demonstrate that the miR-221 zipper attenuates doxorubicin resistance with higher efficiency than anti-miR-221 in human breast cancer cells. Taken together, small RNA zippers are a miRNA inhibitor, which can be used to induce miRNA loss-of-function phenotypes and validate miRNA target genes

Insight into the Interaction of Metal Ions with TroA from Streptococcus suis

The scavenging ability of sufficient divalent metal ions is pivotal for pathogenic bacteria to survive in the host. ATP-binding cassette (ABC)-type metal transporters provide a considerable amount of different transition metals for bacterial growth. TroA is a substrate binding protein for uptake of multiple metal ions. However, the function and structure of the TroA homologue from the epidemic Streptococcus suis isolates (SsTroA) have not been characterized.Here we determined the crystal structure of SsTroA from a highly pathogenic streptococcal toxic shock syndrome (STSS)-causing Streptococcus suis in complex with zinc. Inductively coupled plasma mass spectrometry (ICP-MS) analysis revealed that apo-SsTroA binds Zn(2+) and Mn(2+). Both metals bind to SsTroA with nanomolar affinity and stabilize the protein against thermal unfolding. Zn(2+) and Mn(2+) induce distinct conformational changes in SsTroA compared with the apo form as confirmed by both circular dichroism (CD) and nuclear magnetic resonance (NMR) spectra. NMR data also revealed that Zn(2+)/Mn(2+) bind to SsTroA in either the same site or an adjacent region. Finally, we found that the folding of the metal-bound protein is more compact than the corresponding apoprotein.Our findings reveal a mechanism for uptake of metal ions in S. suis and this mechanism provides a reasonable explanation as to how SsTroA operates in metal transport

Tree-ring stable carbon isotope-based April-June relative humidity reconstruction since AD 1648 in Mt. Tianmu, China

Based on accurate dating, we have determined the stable carbon isotope ratios (delta C-13) of five Cryptomeria fortunei specimens from Mt. Tianmu, a subtropical area in southern China. The five delta C-13 time series records are combined into a single representative delta C-13 time series using a "numerical mix method." These are normalized to remove temporal variations of delta(13) C in atmospheric CO2 to obtain a carbon isotopic discrimination (Delta C-13) time series, in which we observe a distinct correlation between Delta C-13 and local April to June mean relative humidity (RH (AMJ) ) (n = 64, r = 0.858, p < 0.0001). We use this relationship to reconstruct RH (AMJ) variations from ad 1648 to 2014 at Mt. Tianmu. The reconstructed sequence show that over the past 367 years, Mt. Tianmu area was relatively wet, but in the latter part of the twentieth century, under the influence of increasing global warming, it has experienced a sharp reduction in relative humidity. Spatial correlation analysis reveals a significant negative correlation between RH (AMJ) at Mt. Tianmu and Sea Surface Temperature (SSTs) in the western equatorial Pacific and Indian Ocean. In other words, there is a positive correlation between tree-ring delta C-13 in Mt. Tianmu and SSTs. Both observed and reconstructed RH (AMJ) show significant positive correlations with East Asian and South Asian monsoons from 1951 to 2014, which indicate that RH (AMJ) from Mt. Tianmu reflects the variability of the Asian summer monsoon intensity to a great extent. The summer monsoon has weakened since 1960. However, an increase in relative humidity since 2003 implies a recent enhancement in the summer monsoon

Identification of Austwickia chelonae as cause of cutaneous granuloma in endangered crocodile lizards using metataxonomics

The crocodile lizard (Shinisaurus crocodilurus Ahl, 1930) is an endangered reptile species, and in recent years many have died from diseases, especially the rescued and breeding individuals. However, pathogens underlying these diseases are unclear. In this study, we report our effort in rapidly identifying and isolating the pathogen that causes high mortality in crocodile lizards from Guangdong Luokeng Shinisaurus crocodilurus National Nature Reserve. The typical symptom is cutaneous granuloma in the infected crocodile lizards. Metagenomic next-generation sequencing (mNGS) is a comprehensive approach for sequence-based identification of pathogenic microbes. In this study, 16S rDNA based mNGS was used for rapid identification of pathogens, and microscopy and microbe isolation were used to confirm the results. Austwickia chelonae was identified to be the dominant pathogen in the granuloma using 16S rDNA based mNGS. Chinese skinks were used as an animal model to verify the pathogenicity of A. chelonae to fulfill Koch’s postulates. As expected, subcutaneous inoculation of A. chelonae induced granulomas in the healthy Chinese skinks and the A. chelonae was re-isolated from the induced granulomas. Therefore, A. chelonae was the primary pathogen that caused this high mortality disease, cutaneous granuloma, in crocodile lizards from Guangdong Luokeng Shinisaurus crocodilurus National Nature Reserve. Antibiotics analysis demonstrated that A. chelonae was sensitive to cephalothin, minocycline and ampicillin, but not to kanamycin, gentamicin, streptomycin and clarithromycin, suggesting a possible treatment for the infected crocodile lizards. However, surgical resection of the nodules as early as possible was recommended. This study is the first report of pathogenic analysis in crocodile lizards and provides a reference for disease control and conservations of the endangered crocodile lizards and other reptiles. In addition, this study indicated that mNGS of lesions could be used to detect the pathogens in animals with benefits in speed and convenient

Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas

The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma