Autothermal Reforming of Volatile Organic Compounds to Hydrogen-Rich Gas.

Industrial emissions of volatile organic compounds are urgently addressed for their toxicity and carcinogenicity to humans. Developing efficient and eco-friendly reforming technology of volatile organic compounds is important but still a great challenge. A promising strategy is to generate hydrogen-rich gas for solid oxide fuel cells by autothermal reforming of VOCs. In this study, we found a more desirable commercial catalyst (NiO/K2O-γ-Al2O3) for the autothermal reforming of VOCs. The performance of autothermal reforming of toluene as a model compound over a NiO/K2O-γ-Al2O3 catalyst fitted well with the simulation results at the optimum operating conditions calculated based on a simulation using Aspen PlusV11.0 software. Furthermore, the axial temperature distribution of the catalyst bed was monitored during the reaction, which demonstrated that the reaction system was self-sustaining. Eventually, actual volatile organic compounds from the chemical factory (C9, C10, toluene, paraxylene, diesel, benzene, kerosene, raffinate oil) were completely reformed over NiO/K2O-γ-Al2O3. Reducing emissions of VOCs and generating hydrogen-rich gas as a fuel from the autothermal reforming of VOCs is a promising strategy.

Whole genome sequencing of the fast-swimming Southern bluefin tuna (Thunnus maccoyii).

The economically important Southern bluefin tuna (Thunnus maccoyii) is a world-famous fast-swimming fish, but its genomic information is limited. Here, we performed whole genome sequencing and assembled a draft genome for Southern bluefin tuna, aiming to generate useful genetic data for comparative functional prediction. The final genome assembly is 806.54 Mb, with scaffold and contig N50 values of 3.31 Mb and 67.38 kb, respectively. Genome completeness was evaluated to be 95.8%. The assembled genome contained 23,403 protein-coding genes and 236.1 Mb of repeat sequences (accounting for 29.27% of the entire assembly). Comparative genomics analyses of this fast-swimming tuna revealed that it had more than twice as many hemoglobin genes (18) as other relatively slow-moving fishes (such as seahorse, sunfish, and tongue sole). These hemoglobin genes are mainly localized in two big clusters (termed as "MNË® and "LAË® respectively), which is consistent with other reported fishes. However, Thr39 of beta-hemoglobin in the MN cluster, conserved in other fishes, was mutated as cysteine in tunas including the Southern bluefin tuna. Since hemoglobins are reported to transport oxygen efficiently for aerobic respiration, our genomic data suggest that both high copy numbers of hemoglobin genes and an adjusted function of the beta-hemoglobin may support the fast-swimming activity of tunas. In summary, we produced a primary genome assembly and predicted hemoglobin-related roles for the fast-swimming Southern bluefin tuna.

Gut microbiota changes and biological mechanism in hepatocellular carcinoma after transarterial chemoembolization treatment.

Background and aims: Intestinal flora is closely associated with the occurrence and development of hepatocellular carcinoma (HCC). However, gut microbial changes and biological mechanisms in HCC after transarterial chemoembolization (TACE) treatment are rarely reported. Methods: We evaluated changes in intestinal flora after TACE in rabbit HCC models and assessed the impact of these changes on the disease. Twenty-four rabbit VX2 HCC models were established and intestinal flora structures, intestinal barrier function, changes in blood lipopolysaccharide (LPS) levels, Toll-like receptor 4 (TLR4), Cyclooxygenase-2 (COX-2), and p-signal transducer and activator of transcription 3(p-STAT3) protein expression levels were studied after TACE treatment. Results: Compared with healthy rabbits, the intestinal flora in HCC models exhibited structural changes; intestinal barrier function was decreased, and increased LPS levels entered the circulation. A short-term follow-up after TACE showed the procedure partially reversed the intestinal microflora disorder caused by the tumor: intestinal barrier and liver functions were improved, intestinal LPS levels in the blood were reduced, and liver metabolism toward LPS was enhanced. Correlation analyses of the first 75 significantly changed bacteria with clinical factors showed that harmful bacteria had decreased and beneficial bacteria increased. Blood LPS levels and downstream signaling molecule TLR4, COX-2, and p-STAT3 protein expression levels were reduced, which correlated with tumor drug resistance and invasion capabilities. Conclusions: We first characterized gut microbiota changes and biological mechanisms in HCC after TACE treatment. Our data provide a theoretical research basis for TACE combined with an intestinal flora intervention and systemic chemotherapy.

Correlation analysis of serum reproductive hormones and metabolites during multiple ovulation in sheep.

BACKGROUND: The establishment of non-invasive diagnostic method for multiple ovulation prediction is helpful to improve the efficiency of multiple ovulation. The blood hormones and metabolites would be suitable indexes for this subject. METHODS: In this study, 86 estrus ewes (65 of induced estrus (IE) and 21 of spontaneous estrus (SE)) were selected and the blood samples were collected at the day before follicle-stimulating hormone (FSH) injection (1st) and before artificial insemination (2nd). The serum reproductive hormones ofFSH, luteinizing hormone (LH), 17ß-Estradiol (E2), progesterone (P4) and anti-Mullerian hormone (AMH) were measured through enzyme linked immunosorbent assay (ELISA) and the untargeted metabolomics analysis was processed through LC-MS/MS. The embryos were collected after 6.5 days of artificial insemination. RESULTS: In total, 975 and 406 embryos were collected in IE and SE group, respectively. The analysis of reproductive hormones showed that concentrations of FSH, E2 and AMH were positive correlated with the embryo yield while concentrations of LH and P4 were negative correlated in both group at 1st detection. At 2nd detection, the trends of reproductive hormones were similar with 1st except P4, which was positive correlated with embryo yield. The metabolomics analysis showed that 1158 metabolites (721 in positive iron mode and 437 in negative iron mode) were detected and 617 were annotated. In 1st comparation of high and low embryonic yield populations, 56 and 53 differential metabolites were identified in IE and SE group, respectively. The phosphatidyl choline (PC) (19:0/20:5) and PC (18:2/18:3) were shared in two groups. In 2nd comparation, 48 and 49 differential metabolites were identified in IE and SE group, respectively. The PC (18:1/18:2) and pentadecanoic acid were shared. Most differential metabolites were significantly enriched in amino acid, fatty acid metabolism, digestive system secretion and ovarian steroidogenesis pathways. CONCLUSIONS: This study showed that FSH, P4, AMH, the PC relevant metabolites and some anomic acids could be potential biomarkers for embryonic yield prediction in ovine multiple ovulation. The results would help to explain the relation between blood material and ovarian function and provide a theoretical basis for the multiple ovulation prediction.

Circular RNA circ_0000372 contributes to the proliferation, migration and invasion of colorectal cancer by elevating IL6 expression via sponging miR-495.

Circular RNAs are thought to play a vital function in the progression of various cancers, including colorectal cancer (CRC). However, the biological function and mechanism of circ_0000372 in CRC are still not clear. The expression of circ_0000372 and microRNA (miR)-495 was examined by quantitative real-time PCR. Cell proliferation was evaluated using cell counting kit 8 and colony formation assays. Further, cell migration and invasion were assessed using transwell assay. Additionally, western blot analysis was used to detect the expression of proteins associated with proliferation, metastasis, Janus kinase 2 (JAK2)/signal transducers and activators of transcription (STAT3) signaling pathway and interleukin 6 (IL6). Dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to verify the interaction between miR-495 and circ_0000372 or IL6. Furthermore, the effect of circ_0000372 on CRC tumor growth in vivo was explored using the mice xenograft models. Circ_0000372 was markedly upregulated in CRC, and its high expression was associated with the poor prognosis of CRC patients. Silenced circ_0000372 was able to suppress CRC cell proliferation, migration and invasion in vitro and CRC tumor growth in vivo. Bioinformatics prediction and experimental verification proposed that circ_0000372 could sponge miR-495, and miR-495 could target IL6. Besides, the JAK2/STAT3 signaling pathway activation could be regulated by circ_0000372, miR-495 and IL6. Rescue assay results confirmed that the inhibition effect of circ_0000372 knockdown on the proliferation and metastasis of CRC could be reversed by miR-495 inhibitor or IL6 overexpression. In short, we concluded that circ_0000372 promoted CRC progression by regulating the miR-495/IL6 axis, suggesting that circ_0000372 could be used as a new prognostic biomarker and therapeutic target for CRC.

The American Paddlefish Genome Provides Novel Insights into Chromosomal Evolution and Bone Mineralization in Early Vertebrates.

Sturgeons and paddlefishes (Acipenseriformes) occupy the basal position of ray-finned fishes, although they have cartilaginous skeletons as in Chondrichthyes. This evolutionary status and their morphological specializations make them a research focus, but their complex genomes (polyploidy and the presence of microchromosomes) bring obstacles and challenges to molecular studies. Here, we generated the first high-quality genome assembly of the American paddlefish (Polyodon spathula) at a chromosome level. Comparative genomic analyses revealed a recent species-specific whole-genome duplication event, and extensive chromosomal changes, including head-to-head fusions of pairs of intact, large ancestral chromosomes within the paddlefish. We also provide an overview of the paddlefish SCPP (secretory calcium-binding phosphoprotein) repertoire that is responsible for tissue mineralization, demonstrating that the earliest flourishing of SCPP members occurred at least before the split between Acipenseriformes and teleosts. In summary, this genome assembly provides a genetic resource for understanding chromosomal evolution in polyploid nonteleost fishes and bone mineralization in early vertebrates.

Cathodically Pretreated AuNPs-BDD Electrode for Detection of Hexavalent Chromium.

Hexavalent chromium (Cr (VI)) has strong oxidizing properties and can result in strong carcinogenic effects on human bodies. Therefore, it is necessary to detect hexavalent chromium sensitively and accurately. This article proposes the gold nanoparticles (AuNPs)-boron-doped diamond (BDD) electrode for the direct determination of chromium with a green and simple detection process by cathodic stripping voltammetry. Gold nanoparticles are used to enhance the detection performance toward Cr (VI). The effect of different pretreatment methods on electrode modification has been studied, and the detection parameters have been optimized. With the optimized conditions, the AuNPs-BDD electrode presents a good linear behavior in a Cr (VI) concentration range of 10 to 1000 µg/L. A low limit of detection of 1.19 µg/L is achieved. The detection process is simple and environmentally friendly. The sensor has been tested for the detection of Cr (VI) in a real water sample with satisfactory results, which indicates potential application of the AuNPs-BDD electrode for the sensitive and onsite detection of Cr (VI).

Long non-coding RNA KCNQ1OT1 up-regulates CTNND1 by sponging miR-329-3p to induce the proliferation, migration, invasion, and inhibit apoptosis of colorectal cancer cells.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been certified to be involved in the occurrence and growth of diverse cancers, including CRC. The purpose of the research was to explore the effects of lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) on proliferation, migration, invasion, and apoptosis in CRC cells and its mechanism. METHODS: The levels of KCNQ1OT1 and miR-329-3p were examined by quantitative real-time polymerase chain reaction (qRT-PCR) in CRC tissues and cells. The mRNA and protein levels of catenin delta-1 (CTNND1) were measured by qRT-PCR and western blot analysis, respectively. The targets of KCNQ1OT1 and miR-329-3p were predicted by online software and confirmed by luciferase reporter assay. The cell proliferation, migration, invasion, and apoptosis were examined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), transwell, and apoptosis assay. The expression levels of CyclinD1, Bcl-2, MMP9, Cleaved-casp-3, and E-cadherin in SW480 and LS1034 cells were gauged by western blot analysis. Xenograft tumor model was structured to prove the biological role of KCNQ1OT1 of CRC in vivo. RESULTS: The levels of KCNQ1OT1 and CTNND1 were significantly increased in CRC tissues and cells. Knockdown of KCNQ1OT1 suppressed proliferation, migration, invasion, and induced apoptosis in CRC cells. Conversely, CTNND1 overexpression reversed the impact of KCNQ1OT1 knockdown on CRC cells. Moreover, CTNND1 was verified as a direct target of miR-329-3p, and miR-329-3p could specially bind to KCNQ1OT1. Also, the down-regulation of KCNQ1OT1 triggered the CRC progress by up-regulating CTNND1 expression in CRC cells. Besides, KCNQ1OT1 knockdown inhibited CRC tumor growth through the miR-329-3p/CTNND1 axis in vivo. CONCLUSION: Our results indicated that KCNQ1OT1 could positively regulate CTNND1 expression by sponging miR-329-3p, thereby boosting the progression of CRC. Our findings provided the underlying therapy targets for CRC.

Protein phosphatase 2A promotes stomatal development by stabilizing SPEECHLESS in Arabidopsis.

Stomatal guard cells control gas exchange that allows plant photosynthesis but limits water loss from plants to the environment. In Arabidopsis, stomatal development is mainly controlled by a signaling pathway comprising peptide ligands, membrane receptors, a mitogen-activated protein kinase (MAPK) cascade, and a set of transcription factors. The initiation of the stomatal lineage requires the activity of the bHLH transcription factor SPEECHLESS (SPCH) with its partners. Multiple kinases were found to regulate SPCH protein stability and function through phosphorylation, yet no antagonistic protein phosphatase activities have been identified. Here, we identify the conserved PP2A phosphatases as positive regulators of Arabidopsis stomatal development. We show that mutations in genes encoding PP2A subunits result in lowered stomatal production in Arabidopsis Genetic analyses place the PP2A function upstream of SPCH. Pharmacological treatments support a role for PP2A in promoting SPCH protein stability. We further find that SPCH directly binds to the PP2A-A subunits in vitro. In plants, nonphosphorylatable SPCH proteins are less affected by PP2A activity levels. Thus, our research suggests that PP2A may function to regulate the phosphorylation status of the master transcription factor SPCH in stomatal development.

Comprehensive transcriptional changes in the liver of Kanglang white minnow (Anabarilius grahami) in response to the infection of parasite Ichthyophthirius multifiliis.

Abstract: The notorious parasite Ichthyophthirius multifiliis (Ich) has been recorded worldwide in fish species and causes white spot disease, posing major threats and resulting in severe losses to international fish production. Extensively effective strategies for treating Ich are not available yet, and genetic mechanisms of hosts in response to the parasite are still largely unknown. In this study, we selected Kanglang white minnow (KWM, Anabarilius grahami) to examine its liver transcriptional changes after Ich infection, as white spot disease is one bottleneck problem in exploring this economically important species. We divided the experimental fishes into three groups (control, early-infected, and late-infected) to examine differentially expressed genes (DEGs). A total of 831 DEGs were identified and classified into 128 significantly enriched GO (Gene Ontology) terms and 71 significantly enriched KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. Most of these terms or pathways were functionally enriched in immunity, inflammatory response, and apoptosis, such as nucleotide-binding oligomerization domain-like (NOD-like) receptor signaling, tumor necrosis factor (TNF) signaling, interleukin-17 (IL-17) signaling, and apoptosis pathways. We also identified 178 putative antimicrobial peptides (AMPs) and AMP precursors based on our previously reported genome assembly of KWM, and revealed that the expressional patterns varied according to different types. In summary, our work reported the first comprehensive transcriptional changes in KWM in response to the exogenous infection of Ich, which would lay a solid foundation for in-depth studies on disease defense or resistant strains selection in this valuable fish.

Whole Genome Sequencing of Chinese White Dolphin (Sousa chinensis) for High-Throughput Screening of Antihypertensive Peptides.

Chinese white dolphin (Sousa chinensis), also known as the Indo-Pacific humpback dolphin, has been classified as "Vulnerable" on the IUCN Red List of Threatened Species. It is a special cetacean species that lives in tropical and subtropical nearshore waters, with significant differences from other cetaceans. Here, we sequenced and assembled a draft genome of the Chinese white dolphin with a total length of 2.3 Gb and annotation of 18,387 protein-coding genes. Genes from certain expanded families are potentially involved in DNA replication and repairing, suggesting that they may be related to adaptation of this marine mammal to nearshore environments. We also discovered that its historical population had undergone a remarkable bottleneck incident before the Mindel glaciation. In addition, a comparative genomic survey on antihypertensive peptides (AHTPs) among five representative mammals with various residential habitats (such as remarkable differences in exogenous ion concentrations and sea depth) revealed that these small bioactive peptides were highly conserved among these examined mammals, and they had the most abundant hits in collagen subunit proteins, especially for two putative AHTP peptides Gly-Leu-Pro (GLP) and Leu-Gly-Pro (LGP). Our genome assembly will be a valuable resource for further genetic researches on adaptive ecology and conservation biology of cetaceans, and for in-depth investigations into bioactive peptides in aquatic and terrestrial mammals for development of peptide-based drugs to treat various human cardiovascular diseases.

Comparative Transcriptomic Studies on a Cadmium Hyperaccumulator Viola baoshanensis and Its Non-Tolerant Counterpart V. inconspicua.

Many Viola plants growing in mining areas exhibit high levels of cadmium (Cd) tolerance and accumulation, and thus are ideal organisms for comparative studies on molecular mechanisms of Cd hyperaccumulation. However, transcriptomic studies of hyperaccumulative plants in Violaceae are rare. Viola baoshanensis is an amazing Cd hyperaccumulator in metalliferous areas of China, whereas its relative V. inconspicua is a non-tolerant accumulator that resides at non-metalliferous sites. Here, comparative studies by transcriptome sequencing were performed to investigate the key pathways that are potentially responsible for the differential levels of Cd tolerance between these two Viola species. A cascade of genes involved in the ubiquitin proteosome system (UPS) pathway were observed to have constitutively higher transcription levels and more activation in response to Cd exposure in V. baoshanensis, implying that the enhanced degradation of misfolded proteins may lead to high resistance against Cd in this hyperaccumulator. Many genes related to sucrose metabolism, especially those involved in callose and trehalose biosynthesis, are among the most differentially expressed genes between the two Viola species, suggesting a crucial role of sucrose metabolism not only in cell wall modification through carbon supply but also in the antioxidant system as signaling molecules or antioxidants. A comparison among transcriptional patterns of some known transporters revealed that several tonoplast transporters are up-regulated in V. baoshanensis under Cd stress, suggesting more efficient compartmentalization of Cd in the vacuoles. Taken together, our findings provide valuable insight into Cd hypertolerance in V. baoshanensis, and the corresponding molecular mechanisms will be useful for future genetic engineering in phytoremediation.

Thalidomide (THD) alleviates radiation induced lung fibrosis (RILF) via down-regulation of TGF-ß/Smad3 signaling pathway in an Nrf2-dependent manner.

Radiation-induced lung fibrosis (RILF) is a complication of radiotherapy in thoracic cancer patients. Thalidomide (THD) has a therapeutic effect on fibrotic and inflammatory disorders. The purpose of the current study was to investigate the therapeutic effect of THD on RILF in mice and better understand the underlying regulatory mechanisms of the therapeutic effect. We found that THD mitigated the fibrosis caused by irradiation in mice. The action of THD on RILF was related to the elevation of low levels reactive oxygen species (ROS), which inhibited the transforming growth factor­ß (TGF­ß)/Smad3 signaling pathway through activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Analysis of the therapeutic effect of THD using Nrf2-/- mouse model confirmed the role of Nrf2 in vivo. In addition, no radioprotective effect of THD on thoracic cancer cell lines was observed. In conclusion, these data showed that THD attenuated RILF in mice, which was mediated by Nrf2-dependent down-regulation of the TGF-ß/Smad3 pathway, suggesting THD as a potential novel agent for RILF prevention.

Combing NLR, V20 and mean lung dose to predict radiation induced lung injury in patients with lung cancer treated with intensity modulated radiation therapy and chemotherapy.

The purpose was to evaluate the predictive value of baseline neutrophil to lymphocyte ratio (NLR) level in the incidence of grade 3 or higher radiation induced lung injury (RILI) for lung cancer patients. A retrospectively analysis with 166 lung cancer patients was performed. All of the enrolled patients received chemoradiotherapy at our hospital between April 2014 and May 2016. The Cox proportional hazard model was used to identify the potential risk factors for RILI. In this cohort, the incidence of grade 3 or higher RILI was 23.8%. Univariate analysis showed that radiation dose, volume at least received 20Gy (V20), mean lung dose and NLR were significantly associated with the incidence of grade 3 or higher RILI (P = 0.012, 0.008, 0.012, and 0.039, respectively). Multivariate analysis revealed that total dose ≥ 60 Gy, V20 ≥ 20%, mean lung dose ≥ 12 Gy, and NLR ≥ 2.2 were still independent predictive factors for RILI (P = 0.010, 0.043, 0.028, and 0.015, respectively). A predictive model of RILI based on the identified risk factors was established using receiver operator characteristic curves. The results demonstrated that the combination analysis of V20, mean lung dose and NLR was superior to either of the variables alone. Additionally, we found that the constraint of V20 and mean lung dose were meaningful for patients with higher baseline NLR level. If the value of V20 and mean lung dose lower than the threshold value, the incidence of grade 3 or higher RILI for the high NLR level patients could be decreased from 63.3% to 8.7%. Our study showed that radiation dose, V20, mean lung dose and NLR were independent predictors for RILI. Combination analysis of V20, mean lung dose and NLR may provide a more accurate model for RILI prediction.

Improved survival with higher radiation dose for esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy.

PURPOSE: The optimal radiation dose for patients with esophageal squamous cell carcinoma (ESCC) has long been debated. We undertook the retrospective study to evaluate the survival impact of high dose vs standard dose in patients with stage II-III esophageal cancer treated with definitive chemoradiotherapy (CRT). RESULTS: A total of 137 patients were included in our study, 63 patients classified as standard-dose group and 74 as high-dose group. For the 63 patients in the standard-dose group, the median PFS and the 1-, 2-, and 3-year PFS rates were 12.6 months, 58.0%, 26.0% and 12.0%, respectively; for the 74 patients in the high-dose group, they were 20.0 months, 80.1%, 31.0% and 20.0%, respectively (P = 0.013). The median OS of the patients in the standard-dose group and high-dose group groups were 19.0 months and 26.6 months, respectively, and the 1-, 2- and 3-year survival rates were 78.0%, 39.0%, and 24.0% , and 89.0%, 61.0%, and 30.0%, respectively (P = 0.037). Besides the rate of grade ≥ 3 acute irradiation esophagitis in the high-dose group (10.5% versus. 2.2%, P < 0.01), there were no significantly differ of treatment-related toxicities between the two groups. MATERIALS AND METHODS: According to the radiation dose, patients from 2010 to 2014 were allocated into either the standard-dose group (50-50.4 Gy) or the high-dose group (≥ 59.4 Gy). Overall survival (OS), progression-free survival (PFS) and treatment-related toxicities were assessed and compared between the two groups. CONCLUSIONS: Our findings suggest that higher radiation dose could perform better outcomes for esophageal squamous cell carcinoma patients.

High-Throughput Identification of Antimicrobial Peptides from Amphibious Mudskippers.

Widespread existence of antimicrobial peptides (AMPs) has been reported in various animals with comprehensive biological activities, which is consistent with the important roles of AMPs as the first line of host defense system. However, no big-data-based analysis on AMPs from any fish species is available. In this study, we identified 507 AMP transcripts on the basis of our previously reported genomes and transcriptomes of two representative amphibious mudskippers, Boleophthalmus pectinirostris (BP) and Periophthalmus magnuspinnatus (PM). The former is predominantly aquatic with less time out of water, while the latter is primarily terrestrial with extended periods of time on land. Within these identified AMPs, 449 sequences are novel; 15 were reported in BP previously; 48 are identically overlapped between BP and PM; 94 were validated by mass spectrometry. Moreover, most AMPs presented differential tissue transcription patterns in the two mudskippers. Interestingly, we discovered two AMPs, hemoglobin ß1 and amylin, with high inhibitions on Micrococcus luteus. In conclusion, our high-throughput screening strategy based on genomic and transcriptomic data opens an efficient pathway to discover new antimicrobial peptides for ongoing development of marine drugs.

Combining Carcinoembryonic Antigen and Platelet to Lymphocyte Ratio to Predict Brain Metastasis of Resected Lung Adenocarcinoma Patients.

We aimed to evaluate the role of pretreatment carcinoembryonic antigen (CEA) and platelet to lymphocyte ratio (PLR) in predicting brain metastasis after radical surgery for lung adenocarcinoma patients. The records of 103 patients with completely resected lung adenocarcinoma between 2013 and 2014 were reviewed. Clinicopathologic characteristics of these patients were assessed in the Cox proportional hazards regression model. Brain metastasis occurred in 12 patients (11.6%). On univariate analysis, N2 stage (P = 0.013), stage III (P = 0.016), increased CEA level (P = 0.006), and higher PLR value (P = 0.020) before treatment were associated with an increased risk of developing brain metastasis. In multivariate model analysis, CEA above 5.2 ng/mL (P = 0.014) and PLR ≥ 120 (P = 0.036) remained as the risk factors for brain metastasis. The combination of CEA and PLR was superior to CEA or PLR alone in predicting brain metastasis according to the receiver operating characteristic (ROC) curve analysis (area under ROC curve, AUC 0.872 versus 0.784 versus 0.704). Pretreatment CEA and PLR are independent and significant risk factors for occurrence of brain metastasis in resected lung adenocarcinoma patients. Combining these two factors may improve the predictability of brain metastasis.

High-throughput identification of novel conotoxins from the Chinese tubular cone snail (Conus betulinus) by multi-transcriptome sequencing.

BACKGROUND: The venom of predatory marine cone snails mainly contains a diverse array of unique bioactive peptides commonly referred to as conopeptides or conotoxins. These peptides have proven to be valuable pharmacological probes and potential drugs because of their high specificity and affinity to important ion channels, receptors and transporters of the nervous system. Most previous studies have focused specifically on the conopeptides from piscivorous and molluscivorous cone snails, but little attention has been devoted to the dominant vermivorous species. RESULTS: The vermivorous Chinese tubular cone snail, Conus betulinus, is the dominant Conus species inhabiting the South China Sea. The transcriptomes of venom ducts and venom bulbs from a variety of specimens of this species were sequenced using both next-generation sequencing and traditional Sanger sequencing technologies, resulting in the identification of a total of 215 distinct conopeptides. Among these, 183 were novel conopeptides, including nine new superfamilies. It appeared that most of the identified conopeptides were synthesized in the venom duct, while a handful of conopeptides were identified only in the venom bulb and at very low levels. CONCLUSIONS: We identified 215 unique putative conopeptide transcripts from the combination of five transcriptomes and one EST sequencing dataset. Variation in conopeptides from different specimens of C. betulinus was observed, which suggested the presence of intraspecific variability in toxin production at the genetic level. These novel conopeptides provide a potentially fertile resource for the development of new pharmaceuticals, and a pathway for the discovery of new conotoxins.

The Graphene/l-Cysteine/Gold-Modified Electrode for the Differential Pulse Stripping Voltammetry Detection of Trace Levels of Cadmium.

Cadmium(II) is a common water pollutant with high toxicity. It is of significant importance for detecting aqueous contaminants accurately, as these contaminants are harmful to human health and environment. This paper describes the fabrication, characterization, and application of an environment-friendly graphene (Gr)/l-cysteine/gold electrode to detect trace levels of cadmium (Cd) by differential pulse stripping voltammetry (DPSV). The influence of hydrogen overflow was decreased and the current response was enhanced because the modified graphene extended the potential range of the electrode. The Gr/l-cysteine/gold electrode showed high electrochemical conductivity, producing a marked increase in anodic peak currents (vs. the glass carbon electrode (GCE) and boron-doped diamond (BDD) electrode). The calculated detection limits are 1.15, 0.30, and 1.42 µg/L, and the sensitivities go up to 0.18, 21.69, and 152.0 nA·mm-2·µg-1·L for, respectively, the BDD electrode, the GCE, and the Gr/l-cysteine/gold electrode. It was shown that the Gr/l-cysteine/gold-modified electrode is an effective means for obtaining highly selective and sensitive electrodes to detect trace levels of cadmium.

Vaccine-Derived Neutralizing Antibodies to the Human Cytomegalovirus gH/gL Pentamer Potently Block Primary Cytotrophoblast Infection.

UNLABELLED: Human cytomegalovirus (HCMV) elicits neutralizing antibodies (NAb) of various potencies and cell type specificities to prevent HCMV entry into fibroblasts (FB) and epithelial/endothelial cells (EpC/EnC). NAb targeting the major essential envelope glycoprotein complexes gB and gH/gL inhibit both FB and EpC/EnC entry. In contrast to FB infection, HCMV entry into EpC/EnC is additionally blocked by extremely potent NAb to conformational epitopes of the gH/gL/UL128/130/131A pentamer complex (PC). We recently developed a vaccine concept based on coexpression of all five PC subunits by a single modified vaccinia virus Ankara (MVA) vector, termed MVA-PC. Vaccination of mice and rhesus macaques with MVA-PC resulted in a high titer and sustained NAb that blocked EpC/EnC infection and lower-titer NAb that inhibited FB entry. However, antibody function responsible for the neutralizing activity induced by the MVA-PC vaccine is uncharacterized. Here, we demonstrate that MVA-PC elicits NAb with cell type-specific neutralization potency and antigen recognition pattern similar to human NAb targeting conformational and linear epitopes of the UL128/130/131A subunits or gH. In addition, we show that the vaccine-derived PC-specific NAb are significantly more potent than the anti-gH NAb to prevent HCMV spread in EpC and infection of human placental cytotrophoblasts, cell types thought to be of critical importance for HCMV transmission to the fetus. These findings further validate MVA-PC as a clinical vaccine candidate to elicit NAb that resembles those induced during HCMV infection and provide valuable insights into the potency of PC-specific NAb to interfere with HCMV cell-associated spread and infection of key placental cells. IMPORTANCE: As a consequence of the leading role of human cytomegalovirus (HCMV) in causing permanent birth defects, developing a vaccine against HCMV has been assigned a major public health priority. We have recently introduced a vaccine strategy based on a widely used, safe, and well-characterized poxvirus vector platform to elicit potent and durable neutralizing antibody (NAb) responses targeting the HCMV envelope pentamer complex (PC), which has been suggested as a critical component for a vaccine to prevent congenital HCMV infection. With this work, we confirm that the NAb elicited by the vaccine vector have properties that are similar to those of human NAb isolated from individuals chronically infected with HCMV. In addition, we show that PC-specific NAb have potent ability to prevent infection of key placental cells that HCMV utilizes to cross the fetal-maternal interface, suggesting that NAb targeting the PC may be essential to prevent HCMV vertical transmission.