Hyperactivation of SREBP induces pannexin-1-dependent lytic cell death.

Sterol-regulatory element binding proteins (SREBPs) are a conserved transcription factor family governing lipid metabolism. When cellular cholesterol level is low, SREBP2 is transported from the endoplasmic reticulum to the Golgi apparatus where it undergoes proteolytic activation to generate a soluble N-terminal fragment, which drives the expression of lipid biosynthetic genes. Malfunctional SREBP activation is associated with various metabolic abnormalities. In this study, we find that overexpression of the active nuclear form SREBP2 (nSREBP2) causes caspase-dependent lytic cell death in various types of cells. These cells display typical pyroptotic and necrotic signatures, including plasma membrane ballooning and release of cellular contents. However, this phenotype is independent of the gasdermin family proteins or mixed lineage kinase domain-like (MLKL). Transcriptomic analysis identifies that nSREBP2 induces expression of p73, which further activates caspases. Through whole-genome CRISPR-Cas9 screening, we find that Pannexin-1 (PANX1) acts downstream of caspases to promote membrane rupture. Caspase-3 or 7 cleaves PANX1 at the C-terminal tail and increases permeability. Inhibition of the pore-forming activity of PANX1 alleviates lytic cell death. PANX1 can mediate gasdermins and MLKL-independent cell lysis during TNF-induced or chemotherapeutic reagents (doxorubicin or cisplatin)-induced cell death. Together, this study uncovers a noncanonical function of SREBPs as a potentiator of programmed cell death and suggests that PANX1 can directly promote lytic cell death independent of gasdermins and MLKL.

Similar neurotoxin expression profiles of traditional Chinese scorpion medicine material between juvenile and adult Mesobuthus martensii scorpions revealed by multiple strategic proteomics.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mesobuthus martensii scorpions, called as "Quanxie", are known Chinese medicinal material base on the "Combat poison with poison" strategy for more than one thousand years, and still widely used to treat various diseases according to the Pharmacopoeia of the People's Republic of China nowadays. AIM OF STUDY: The study aims to investigate the similarity of scorpion neurotoxins at the protein level between the juvenile and adult Mesobuthus martensii scorpions as Chinese medicine materials. MATERIALS AND METHODS: The second-, third- and fourth-instar, and adult Mesobuthus martensii scorpions were collected for the characterization of neurotoxin expression through multiple strategic proteomics, including undigested scorpion venom, endopeptidase-digested, and undigested scorpion telson extract for the sample analysis. RESULTS: Based on the known 107 scorpion neurotoxins from the genomic and transcriptomic analysis of adult Mesobuthus martensii scorpions, the multiple strategic proteomics first revealed that neurotoxins exhibited more stability in telson extract than secreted venom. In the reported transcripts of scorpion neurotoxins, approximately 53%, 56%, 66% and 78% of neurotoxins were detected through undigested scorpion venom, the endopeptidase Arg-C-, Lys-C-digested telson extract, and undigested telson extract strategies, respectively. Nearly 79% of scorpion neurotoxins detected in third-instar Mesobuthus martensii scorpions represent the largest number of scorpion neurotoxins from proteomic analysis to date. Moreover, a total of 84% of scorpion neurotoxins were successfully identified at the protein level, and similar neurotoxin expression profiles in second-, third- and fourth-instar, and adult Mesobuthus martensii scorpions were first revealed by the multiple strategic proteomics. CONCLUSION: These findings for the first time demonstrate the similar neurotoxin expression profiles between the juvenile and adult Mesobuthus martensii scorpions as Chinese medicinal material, which would serve as a paradigm for further toxin analysis from different venomous animals.

Scutellarin ameliorates diabetic nephropathy via TGF-ß1 signaling pathway.

Breviscapine, a natural flavonoid mixture derived from the traditional Chinese herb Erigeron breviscapus (Vant.) Hand-Mazz, has demonstrated a promising potential in improving diabetic nephropathy (DN). However, the specific active constituent(s) responsible for its therapeutic effects and the underlying pharmacological mechanisms remain unclear. In this study, we aimed to investigate the impact of scutellarin, a constituent of breviscapine, on streptozotocin-induced diabetic nephropathy and elucidate its pharmacological mechanism(s). Our findings demonstrate that scutellarin effectively ameliorates various features of DN in vivo, including proteinuria, glomerular expansion, mesangial matrix accumulation, renal fibrosis, and podocyte injury. Mechanistically, scutellarin appears to exert its beneficial effects through modulation of the transforming growth factor-ß1 (TGF-ß1) signaling pathway, as well as its interaction with the extracellular signal-regulated kinase (Erk) and Wnt/ß-catenin pathways.

Scutellarin ameliorates diabetic nephropathy via TGF-ß1 signaling pathway.

Breviscapine, a natural flavonoid mixture derived from the traditional Chinese herb Erigeron breviscapus (Vant.) Hand-Mazz, has demonstrated a promising potential in improving diabetic nephropathy (DN). However, the specific active constituent(s) responsible for its therapeutic effects and the underlying pharmacological mechanisms remain unclear. In this study, we aimed to investigate the impact of scutellarin, a constituent of breviscapine, on streptozotocin-induced diabetic nephropathy and elucidate its pharmacological mechanism(s). Our findings demonstrate that scutellarin effectively ameliorates various features of DN in vivo, including proteinuria, glomerular expansion, mesangial matrix accumulation, renal fibrosis, and podocyte injury. Mechanistically, scutellarin appears to exert its beneficial effects through modulation of the TGF-ß1 signaling pathway, as well as its interaction with the Erk and Wnt/ß-catenin pathways.

Contrasting effects of different light regimes on the photoreactivities of allochthonous and autochthonous chromophoric dissolved organic matter.

Chromophoric dissolved organic matter (CDOM) plays an important role in ultraviolet (UV) light absorption in the ocean. CDOM is known to originate from either an allochthonous or autochthonous source and has varying compositions and levels of reactivity; however, the effects of individual radiation treatments and the combined effects of UVA and UVB on allochthonous and autochthonous CDOM remain poorly understood. Thus, here, we measured changes in the common optical properties of CDOM collected from China's marginal seas and the Northwest Pacific, using full-spectrum, UVA (315-400 nm), and UVB (280-315 nm) irradiation to induce photodegradation over the same time period (60 h). Excitation-emission matrices (EEMs) combined with parallel factor analysis (PARAFAC) identified four components: marine humic-like C1, terrestrial humic-like C2, soil fulvic-like C3, and tryptophan-like C4. Although the behaviours of these components during full-spectrum irradiation exhibited similar decreasing tendencies, three components (C1, C3, and C4) underwent direct photodegradation under UVB exposure, whereas C2 was more susceptible to UVA degradation. The diverse photoreactivities of the source-dependent components to different light treatments led to differing photochemical behaviours of other optical indices [aCDOM(355), aCDOM(254), SR, HIX, and BIX]. The results indicate that irradiation preferentially reduced the high humification degree or humic substance content of allochthonous DOM, and promoted the transformation from the allochthonous humic DOM components to recently produced components. Although values for the samples from different sources overlapped frequently, principal component analysis (PCA) indicated that the overall optical signatures could be linked to the original CDOM source features. The degradation of CDOM humification, aromaticity, molecular weight, and autochthonous fractions under exposure can drive the CDOM biogeochemical cycle in marine environments. These findings can aid in a better understanding of the effects of different combinations of light treatments and CDOM characteristics on CDOM photochemical processes.

Low absolute CD4+ T cell counts in peripheral blood: an independent predictor of inferior survival in natural killer/T-cell lymphoma-a retrospective cohort study.

Background: Lymphopenia at diagnosis is considered a negative prognostic factor for patients with extra-nodal natural killer (NK)/T-cell lymphoma (ENKTL), especially that of the absolute cluster of differentiation 4+ T cell count (ACD4C), which has previously been identified as an independent prognostic factor in other hematologic malignancies. However, there is limited data available regarding the prognostic value of peripheral blood T lymphocyte subsets in ENKTL patients. The purpose of this study was to investigate the prognostic value of lymphocyte subsets, especially the ACD4C in ENKTL as a clinical biomarker. Methods: We analyzed the clinical data of 176 patients who met the inclusion criteria in Cancer Center of Integrated Hospital of Traditional Chinese Medicine, Southern Medical University from 2000 to 2018, including baseline clinical factors and ACD4C detected by flow cytometry, and examined the correlation between the results and clinical parameters and long-term outcomes. Results: The complete response rate of the high ACD4C group was 57.6%, which was significantly higher than that of the low ACD4C group (15.1%, P<0.001). The univariate analysis results showed that at a median follow-up time of 58.2 months, patients with a high ACD4C had significantly superior progression-free survival (PFS) and overall survival (OS) (P=0.034 and P=0.001, respectively). The multivariate analysis results revealed that Eastern Cooperative Oncology Group performance status (ECOG PS) and the ACD4C were independent prognostic factors for OS [RR (95% CI): 2.288 (1.209-4.328), P=0.011 and RR (95% CI): 2.058 (1.070-3.968), P=0.031, respectively]. ECOG PS was also an independent prognostic factor for PFS [RR (95% CI): 1.858 (1.064-3.244), P=0.029], while ACD4C tended to be independently correlated with PFS (P=0.085). Conclusions: In this large cohort study, we found that the ACD4C was associated with survival outcomes in ENKTL patients. It is a potential biomarker, which may potentially be applied to clinical.

Characteristics and Health Risk Assessment of Heavy Metal Pollution in Haikou Bay and Adjacent Seas.

Heavy metal contamination in coastal waters may pose a serious threat to aquatic products and human health. This study aimed to gain a better understanding of the pollution-induced by heavy metals in Haikou Bay and adjacent seas and assessed the potential ecological risk. The spatial distributions of heavy metals including Cu, Pb, Zn, Cd, Cr, Hg, and As were analyzed in the surface and bottom water, surface sediment, and five species of fish collected from Haikou Bay and adjacent seas. For seawater, the results showed that the horizontal distribution of the seven heavy metal elements in the study area had no uniform pattern due to the influence of complex factors, such as land-based runoff, port shipping, and ocean current movement. In contrast, the vertical distribution of these heavy metal elements, except for Zn and Cd, showed high concentrations in the surface water and low concentrations in the bottom water. Due to the symbiotic relationship between Zn and Cd, the distributions of these two elements were similar in the study areas. Different from the complex distribution of heavy metals in water, the highest concentrations of these elements in surface sediment all occurred at station 11 except for Pb. Our study revealed that organic carbon and sulfide are important factors affecting the heavy metal concentrations in the surface sediments. Heavy metals in waters and surface sediment were lower than the quality standard of class I according to the China National Standard for Seawater Quality and the sediment quality, except for Zn in water, suggesting that the seawater and surface sediment in Haikou Bay and adjacent seas has not been polluted by heavy metals. Additionally, the heavy metal As was the main element affecting the quality of fish in this study area, and attention should be paid in the future. The target hazard quotient (THQ) values of seven heavy metal elements in fish were all lower than 1.0, indicating that eating fish in this area will not pose a risk to human health. These results provide valuable information for further understanding the status of heavy metal pollution in Haikou Bay and adjacent seas and the development of targeted conversation measures for the environment and fish consumers.

Taxonomic and Bioactivity Characterizations of Mameliella alba Strain LZ-28 Isolated from Highly Toxic Marine Dinoflagellate Alexandrium catenella LZT09.

Microalgae host varied microbial consortium harboring cross-kingdom interactions with fundamental ecological significance in aquatic ecosystems. Revealing the complex biofunctions of the cultivable bacteria of phycosphere microbiota is one vital basis for deeply understanding the mechanisms governing these dynamic associations. In this study, a new light-yellow pigmented bacterial strain LZ-28 was isolated from the highly-toxic and harmful algal bloom-forming dinoflagellate Alexandrium catenella LZT09. Collective phenotypic and genotypic profiles were obtained to confidently identify this strain as a new Mameliellaalba member. Comparative genomic analysis showed that strain LZ-28 shared highly similar functional features with other four marine algae-derived M. alba strains in spite of their distinctive isolation sources. Based on the bioactivity assaying, the mutual growth-promoting effects between bacterial strain LZ-28 and algal strain LZT09 were observed. After the culture conditions were optimized, strain LZ-28 demonstrated an extraordinary production ability for its bioflocculanting exopolysaccharides (EPS). Moreover, the portions of two monosaccharides glucose and fucose of the EPS were found to positively contribute to the bioflocculanting capacity. Therefore, the present study sheds light on the similar genomic features among the selected M. alba strains, and it also reveals the potential pharmaceutical, environmental and biotechnological implications of active EPS produced by this new Mameliella alba strain LZ-28 recovered from toxic bloom-forming marine dinoflagellate.

Alexandriicola marinus gen. nov., sp. nov., a new member of the family Rhodobacteraceae isolated from marine phycosphere.

Two yellow-pigmented bacterial strains, LZ-14 T and ABI-LZ29, were isolated from the cultivable phycosphere microbiota of the highly toxic marine dinoflagellate Alexandrium catenella LZT09 and demonstrated obvious microalgae growth-promoting potentials toward the algal host. To elucidate the taxonomic status of the two bioactive bacterial strains, they were subjected to a polyphasic taxonomic characterization. Both strains were found to be Gram-negative, aerobic, rod-shaped and motile; to contain Q-10 as the predominant ubiquinone; summed feature 8, C16:0, C18:1 ω7c 11-methyl and summed feature 3 as the major fatty acids; and diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and two unidentified phospholipids as the predominant polar lipids. Based on the phylogenetic analysis, phylogenomic inferences and phenotypic characteristics, the strains could be clearly distinguished from phylogenetically closely related species and formed a distinct monophyletic lineage in the family Rhodobacteraceae. The size of the draft genome of strain LZ-14 T is 4.615 Mb, with a DNA G + C content of 63.3 mol%. It contains ten predicted secondary metabolite biosynthetic gene clusters and core genes for bacterial exopolysaccharide biosynthesis. Therefore, strain LZ-14 T (= CCTCC AB 2017230 T = KCTC 62342 T) represents a novel species of a new genus, for which the name Alexandriicola marinus gen. nov., sp. nov., is proposed.

Gephyromycinifex aptenodytis gen. nov., sp. nov., isolated from gut of Antarctic emperor penguin Aptenodytes forsteri.

A novel actinobacterium NJES-13T was isolated from the gut of Antarctic emperor penguin Aptenodytes forsteri. The new isolate produces bioactive gephyromycin metabolites and exopolysaccharides (EPS). Cells were Gram-negative, motile with the peritrichous flagella, and with a faint layer of extracellular slime. Colonies were yellow when grown on marine agar, ISP1, 2, 4 and TSA media. The strain developed clusters of coccoid, and divided by binary fission in the early phase of growth. The cell clusters were gradually disrupted during the stationary phase and formed short rod-shape cells which were interconnected by viscous EPS showing a three-dimensional net-like morphology, and contained polyhydroxyalkanoates (PHA) granules inside the cells. Growth of strain NJES-13T was observed at 15-45 °C, at pH 6.0-9.0 with 0.5-9.0% (w/v) NaCl. The complete genomic size of strain NJES-13T was 3.45 Mb with a DNA G + C content of 67.0 mol%. The combined polyphasic taxonomic characterizations presented in this study unequivocally separated strain NJES-13T from all known genera in the family Dermatophilaceae. Thus, strain NJES-13T represents a novel species of a new genus, for which the name Gephyromycinifex aptenodytis gen. nov., and sp. nov. is proposed. The type strain is NJES-13T (= CCTCC 2019007T = KCTC 49281T). Genetic prediction of secondary metabolite biosynthesis revealed a 44.5 kb-long biosynthetic gene cluster (BGC) of type III polyketide synthase (PKS) as well as four other BGCs, indicating its great potential to produce novel bioactive metabolites derived from the gut microbiota of animals living in the extreme habitats in the Antarctica.

Trace metal contamination and species-specific bioaccumulation in the Zhoushan Fishery, northwestern East China Sea.

Metal contamination in fishery water may pose a serious threat to aquatic products and human health. In this study, the contents of seven trace metals were assessed in water, sediment, and ten commercially important species (seven fish and three crustaceans) with different trophic guilds, habitat preferences, and motility, collected from the Zhoushan Fishery, northwest East China Sea. In general, the results showed that the concentrations of trace metals in water and sediment were lower than the safety thresholds set by the National Seawater Quality Standard of China and the sediment quality guidelines, except for Cu, As, and Cr in sediment. The high metal concentrations were spatially distributed in the west of the Zhoushan Fishery, which is probably due to the chemical pollution generated from many large international ports and chemical industries in Hangzhou Bay. The metal concentrations in the species were lower than the legislation thresholds established by the Commission Regulation and China National Standard, except for Cd in two crustacean species. However, a health risk assessment indicated that the consumption of the analyzed seafood is safe. However, there is a potential risk to local consumers who prefer crustaceans. From a species-specific bioaccumulation point of view, species in high trophic guilds, benthivores, species with low motility, or those living near the sediment have been found to be most likely to accumulate metals. Our findings could contribute to the understanding of the accumulation tendencies of metals in species of different trophic guilds with varying habitat preferences and motility and provide valuable data to environmental and seafood safety managers.

Fabrication of gradient anisotropic cellulose hydrogels for applications in micro-strain sensing.

A gradient anisotropic cellulose hydrogel was prepared by the diffusion of CaCl2 solution. The degree of orientation of the cellulose chains decreased along the ion diffusion direction, and the birefringence of the highly oriented area was up to 1.323×10-4. Importantly, we first propose and demonstrate the presence of sensitive region in the gradient anisotropy hydrogel. The sensitive region located in the order-disorder transition displayed large color variation with the optical path difference (R) range from 155 nm to 1200 nm, high sensitivity (1 % strain interval), low detection (minimum 1 % strain), good cycling ability of 50 times and frost resistance at -20℃. Based on this, the readable response colorimetric card was designed for micro-strain detection. The programmable Ca2+ diffusion design made it convenient to fabricate cylindrical and tubular hydrogels. This concept of sensitive region and this flexible strategy will broaden new horizons to materials that have excellent responsive properties for optical applications, sensors and multiscale bionics architectures.

Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from Gephyromycinifex aptenodytis gen. nov., sp. nov.

Strain NJES-13T is the type strain and currently the only species of the newly established actinobacteria genera Aptenodytes in the family Dermatophilaceae isolated from the gut microbiota of the Antarctic emperor penguin. This strain demonstrated excellent bioflocculation activity with bacteria-derived exopolysaccharides (EPSs). Moreover, it produced bioactive angucycline/angucyclinone derivatives (ADs) and contained one type III polyketide synthase (T3PKS), thus demonstrating great potential to produce novel bioactive compounds. However, the low productivity of the potential new AD metabolite was the main obstacle for its chemical structure elucidation. In this study, to increase the concentration of targeted metabolites, the influence of cellular morphology on AD metabolism in strain NJES-13T was determined using glass bead-enhanced fermentation. Based on the cellular ultra-structural observation driven by bacterial EPSs, and quantitative analysis of the targeted metabolites, the successful increasing of the productivity of three AD metabolites was achieved. Afterward, a new frigocyclinone analogue was isolated and then identified as 2-hydroxy-frigocyclinone, as well as two other known ADs named 2-hydroxy-tetrangomycin (2-HT) and gephyromycin (GPM). Three AD metabolites were found to demonstrate different bioactivities. Both C-2 hydroxyl substitutes, 2-hydroxy-tetrangomycin and 2-hydroxy-frigocyclinone, exhibited variable inhibitory activities against Staphylococcus aureus, Bacillus subtilis and Candida albicans. Moreover, the newly identified 2-hydroxy-frigocyclinone also showed significant cytotoxicity against three tested human-derived cancerous cell lines (HL-60, Bel-7402 and A549), with all obtained IC50 values less than 10 µM. Based on the genetic analysis after genomic mining, the plausible biogenetic pathway of the three bioactive ADs in strain NJES-13T was also proposed.

Dynamics of denitrification performance and denitrifying community under high-dose acute oxytetracycline exposure and various biorecovery strategies in polycaprolactone-supported solid-phase denitrification.

Solid-phase denitrification (SPD) is a promising technology for nitrate-rich water purification. This study aimed to examine the variation in denitrification performance and denitrifying community under high-dose acute oxytetracycline (OTC) exposure and various biorecovery strategies. The denitrification performance was impaired significantly after one-day OTC shock at 50 mg L-1 in a continuous-flow SPD system supported by a polycaprolactone (PCL) carrier but could rapidly recover without the addition of OTC. When 50 mg L-1 OTC stress was applied for a longer time in the batch tests, a natural recovery period of more than 20 days was required to reach more than 95% nitrate reduction. Under the same conditions, the addition of both mature biofilm-attached PCL carrier and fresh biofilm-free PCL carrier significantly shortened the recovery time for efficient nitrate reduction, mainly due to the increase in organic availability from the PCL carriers. However, the composition of the microbial community notably changed due to the effects of OTC according to high-throughput sequencing and metagenomic analysis. Genes encoding NAR and NIR were much more sensitive than those encoding NOR and NOS to OTC shock. Tetracycline resistance gene (TRG) enrichment was 15.86% higher in the biofilm that experienced short-term OTC shock than in the control biofilm in the continuous-flow SPD system.

Species-specific bioaccumulation of trace metals among fish species from Xincun Lagoon, South China Sea.

Xincun Lagoon is an important fishing area in northern Hainan Island, China. It has long been exposed to pollutants from local sewage, breeding cages and fishing boats, resulting in serious pollution threats to the survival of fish. In this study, we examined the concentrations of seven trace metals (Cu, Pb, Zn, Cd, Hg, As and Cr) in sixteen economic fish species collected from Xincun Lagoon and their exposed environment (water and sediment). The concentrations of Pb and Zn in the water column were higher than the safety threshold stipulated by Chinese legislation, while the contents of all examined metals in the sediment and fish species were lower than the legislative thresholds set by China and international organizations. The contents of trace metals in the fish species in high trophic levels or those that prefer to live in/on the sediment layer were significantly higher than those in other trophic levels and pelagic/subbenthic fish, these species had homogeneous anthropogenic pollution sources for Cu, Zn, Cd, Hg and As. Our results show that the trace metal contents in fish were mainly affected by trophic level and habitat preference. The contribution of metal exposure from the sediment to metal accumulation in fish was lower than that in water, especially for the Cd and Hg in the sediment. These results provide valuable information for further understanding the species-specific patterns of metal accumulation in fish and the development of targeted conservation measures for the environment and fish consumers.

Correction: Preoperative Prediction of Ki-67 Labeling Index By Three-dimensional CT Image Parameters for Differential Diagnosis Of Ground-Glass Opacity (GGO).

[This corrects the article DOI: 10.1371/journal.pone.0129206.].

FKBP3 Promotes Proliferation of Non-Small Cell Lung Cancer Cells through Regulating Sp1/HDAC2/p27.

FKBP3 is a member of FK506-binding proteins (FKBPs). Little is known about the expression and functional role(s) of FKBP3 in non-small cell lung cancer (NSCLC). In the present study, we demonstrated up-regulation of FKBP3 expression, both at mRNA and protein levels, in NSCLC samples which closely correlated with poor survival in NSCLC patients. In vitro and in vivo experiments revealed that FKBP3 could promote NSCLC cell proliferation. Furthermore, knockdown of FKBP3 significantly decreased histone deacetylase 2 (HDAC2) expression and increased p27 (a cell cycle inhibitor) expression. HDAC2 modulated the acetylation of histone H3K4 by directly binding to the p27 promoter. The proliferation-promoting effect of FKBP3 was dependent on HDAC2 and inhibited by p27. Also, FKBP3 induced HDAC2 promoter activity via inhibiting the ubiquitination of transcription factor Sp1. Additionally, we identified miR-145-5p as a regulator of FKBP3. miR-145-5p overexpression suppressed cell proliferation of NSCLC cells which was abrogated by FKBP3 overexpression. Taken together, our data clearly show that FKBP3/Sp1/HDAC2/p27 control cell proliferation during NSCLC development.

Photochemical behavior of dissolved and colloidal organic matter in estuarine and oceanic waters.

Chromophoric dissolved organic matter (CDOM), carbohydrates, and amino acids were analyzed to investigate the photochemistry of total dissolved (<0.22µm) organic matter (DOM), high-molecular-weight (HMW, 1kDa-0.22µm) DOM and low-molecular-weight (LMW, <1kDa) DOM at stations in the Yangtze River and its coastal area, and in the Western Pacific Ocean. Results revealed that the humic-like and tryptophan-like CDOM fluorescent components in riverine, coastal, and oceanic surface waters were photodegraded during irradiation. However, the photochemical behavior of tyrosine-like component was obscured by the excessive fluorescence intensities of humic- and tryptophan-like fluorescent components. Light sensitivity varied depending on the source material; terrestrially derived DOM was more susceptible to irradiation than autochthonous DOM. In contrast to the expected photodegradation of CDOM, photo-induced synthetic reaction transformed the LMW matters to polysaccharides (PCHO) and degradation reaction decomposed the HMW DOM to Monosaccharides. Colloidal DOM preferentially underwent photodegradation, whereas permeate DOM mainly photosynthesized PCHO. The total hydrolysable amino acid (THAA) pool changed because of the additional input by the photodegradation of DOM or THAA itself. The compositions of THAA changed during the irradiation experiments, indicating that the different photochemical behavior of individual amino acids were related to their different original photoreactivities; the relatively stable amino acids (e.g., Ser and Gly) significantly accumulated during irradiation, whereas photo-active aromatic amino acids (e.g. Tyr and His) were prone to photodegradation. The data presented here demonstrated that irradiation significantly influence the conversion between dissolved and colloid organic matter. These results can promote the understanding of irradiation effect on the carbon and nitrogen cycle in riverine, estuarine and oceanic ecosystems.

Role of high expression levels of STK39 in the growth, migration and invasion of non-small cell type lung cancer cells.

Non-small cell type lung cancer (NSCLC) is the most common malignancy and the leading cause of cancer related mortality. In this study, serine/threonine kinase 39 (STK39) was identified as an up-regulated gene in NSCLC tissues by next-generation RNA sequencing. Although STK39 gene polymorphisms may be prognostic of overall survival in patients with early stage NSCLC, the roles of STK39 in NSCLC cancer are poorly understood. In the current study, Genome Set Enrichment Analysis (GSEA) on the RNA-seq data of NSCLC specimens indicated that cancer-related process and pathways, including metastasis, cell cycle, apoptosis and p38 pathway, were significantly correlated with STK39 expression. STK39 expression was significantly increased in NSCLC cases and its protein expression was positively correlated with the poor tumor stage, large tumor size, advanced lymphnode metastasis and poor prognosis. Down-regulation of STK39 in NSCLC cells significantly decreased cell proliferation by blocking of cell cycle and inducing apoptosis. We also found that STK39 knockdown in NSCLC cells remarkably repressed cell migration and invasion. On the contrary, overexpression of STK39 in NSCLC cells had inverse effects on cell behaviors. Taken together, STK39 acts as a tumor oncogene in NSCLC and can be a potential biomarker of carcinogenesis.

Overexpression and biological function of TMEM48 in non-small cell lung carcinoma.

Transmembrane protein 48 (TMEM48), localized to nuclear pore complexes (NPCs), has been reported crucial for NPC assembly. Alterations in NPC members have been reported in several malignancies. The present study was aimed to elucidate the expression and biological function of TMEM48 in non-small cell lung carcinoma (NSCLC). Here, TMEM48 expression level was higher in NSCLC tissues than that in the adjacent normal tissues. Moreover, higher TMEM48 expression was correlated with a more advanced tumor stage, lymph node metastasis, bigger tumor size tumor stage, and shorter survival time. Knockdown of TMEM48 in NSCLC cell lines, A549 and H1299, inhibited cell proliferation and significantly increased cells population in G1 phase. Gene set enrichment analysis (GSEA) showed that cell cycle pathway was correlative with the TMEM48 expression. Additionally, real-time PCR and western blot analysis revealed that several cell cycle and DNA replication genes, including Cyclin B1, CDK1, CDC6, PCNA, and RCF4, were reduced after TMEM48 knockdown. Additionally, inhibition of TMEM48 in NSCLC cells significantly stimulated cell apoptosis, while notably repressed cell adhesion, migration, invasion, and tumorigenicity in nude mice. Our data provide insight into the biological relevance of TMEM48 in NSCLC progression and highlight its usefulness as a prognostic factor and potential therapeutic target in NSCLC.