Evaluation of the tumor-targeting specific imaging and killing effect of a CEA-targeting nanoparticle in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is a prevalent digestive malignancy with significant global mortality and morbidity rates. Improving diagnostic capabilities for CRC and investigating novel therapeutic approaches are pressing clinical imperatives. Additionally, carcinoembryonic antigen (CEA) has emerged as a highly promising candidate for both colorectal tumor imaging and treatment. METHODS: A novel active CEA-targeting nanoparticle, CEA(Ab)-MSNs-ICG-Pt, was designed and synthesized, which served as a tumor-specific fluorescence agent to help in CRC near-infrared (NIR) fluorescence imaging. In cell studies, CEA(Ab)-MSNs-ICG-Pt exhibited specific targeting to RKO cells through specific antibody-antigen binding of CEA, resulting in distribution both within and around these cells. The tumor-targeting-specific imaging capabilities of the nanoparticle were determined through in vivo fluorescence imaging experiments. Furthermore, the efficacy of the nanoparticle in delivering chemotherapeutics and its killing effect were evaluated both in vitro and in vivo. RESULTS: The CEA(Ab)-MSNs-ICG-Pt nanoparticle, designed as a novel targeting agent for carcinoembryonic antigen (CEA), exhibited dual functionality as a targeting fluorescent agent. This CEA-targeting nanoparticle showed exceptional efficacy in eradicating CRC cells in comparison to individual treatment modalities. Furthermore, it exhibits exceptional biosafety and biocompatibility properties. CEA(Ab)-MSNs-ICG-Pt exhibits significant promise due to its ability to selectively target tumors through NIR fluorescence imaging and effectively eradicate CRC cells with minimal adverse effects in both laboratory and in vivo environments. CONCLUSION: The favorable characteristics of CEA(Ab)-MSNs-ICG-Pt offer opportunities for its application in chemotherapeutic interventions, tumor-specific NIR fluorescence imaging, and fluorescence-guided surgical procedures.

Magnetoelectric Sensor Operating in d15 Thickness-Shear Mode for High-Frequency Current Detection.

For the application of high-frequency current detection in power systems, such as very fast transient current, lightning current, partial discharge pulse current, etc., current sensors with a quick response are indispensable. Here, we propose a high-frequency magnetoelectric current sensor, which consists of a PZT piezoelectric ceramic and Metglas amorphous alloy. The proposed sensor is designed to work under d15 thickness-shear mode, with the resonant frequency around 1.029 MHz. Furthermore, the proposed sensor is fabricated as a high-frequency magnetoelectric current sensor. A comparative experiment is carried out between the tunnel magnetoresistance sensor and the magnetoelectric sensor, in the aspect of high-frequency current detection up to 3 MHz. Our experimental results demonstrate that the d15 thickness-shear mode magnetoelectric sensor has great potential for high-frequency current detection in smart grids.

Prognostic and predictive value of tumor deposits in advanced signet ring cell colorectal cancer: SEER database analysis and multicenter validation.

BACKGROUND: Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer with a bleak prognosis. The relationship between its clinicopathological features and survival remains incompletely elucidated. Tumor deposits (TD) have been utilized to guide the N staging in the 8th edition of American Joint Committee on Cancer (AJCC) staging manual, but their prognostic significance remains to be established in colorectal SRCC. PATIENTS AND METHODS: The subjects of this study were patients with stage III/IV colorectal SRCC who underwent surgical treatment. The research comprised two cohorts: a training cohort and a validation cohort. The training cohort consisted of 631 qualified patients from the SEER database, while the validation cohort included 135 eligible patients from four independent hospitals in China. The study assessed the impact of TD on Cancer-Specific Survival (CSS) and Overall Survival (OS) using Kaplan-Meier survival curves and Cox regression models. Additionally, a prognostic nomogram model was constructed for further evaluation. RESULTS: In both cohorts, TD-positive patients were typically in the stage IV and exhibited the presence of perineural invasion (PNI) (P < 0.05). Compared to the TD-negative group, the TD-positive group showed significantly poorer CSS (the training cohort: HR, 1.87; 95% CI, 1.52-2.31; the validation cohort: HR, 2.43; 95% CI, 1.55-3.81; all P values < 0.001). This association was significant in stage III but not in stage IV. In the multivariate model, after adjusting for covariates, TD maintained an independent prognostic value (P < 0.05). A nomogram model including TD, N stage, T stage, TNM stage, CEA, and chemotherapy was constructed. Through internal and external validation, the model demonstrated good calibration and accuracy. Further survival curve analysis based on individual scores from the model showed good discrimination. CONCLUSION: TD positivity is an independent factor of poor prognosis in colorectal SRCC patients, and it is more effective to predict the prognosis of colorectal SRCC by building a model with TD and other clinically related variables.

Predation risk-mediated indirect effects promote submerged plant growth: Implications for lake restoration.

Biological manipulation, involving fish stockings, is commonly used to counteract the deterioration of submerged vegetation in eutrophic lakes. Nevertheless, the non-consumptive effects (NCEs) of stocked carnivorous fish are often overlooked. Using a controlled experimental system, we investigated the NCEs of a native carnivorous fish, snakehead (Channa argus), on two key biological factors, herbivore-dominated grass carp (Ctenopharyngodon idella) and disturbance-dominated loach (Misgurnus anguillicaudatus), influencing submerged plants growth. Additionally, we conducted a meta-analysis on predation risk and primary productivity. The results reveal that predation risk induces oxidative stress damage and affects grass carp growth. Non-significant changes in cortisol and glucose may be linked to predation risk prediction. Simultaneously, predation risk reduces fish feeding and disturbance behavior, relieving pressure on submerged plants to be grazed and disturbed, thereby supporting plant development. The presence of submerged plants, in turn, enhances loach activity and influences water body characteristics through negative feedback. Furthermore, the meta-analysis results indicate the facilitative effect of predation risk on primary producers. Our findings contribute to the understanding of biological manipulation theory. We demonstrate that the predation risk associated with introducing carnivorous fish can promote the growth of submerged plants through behaviorally mediated indirect effects. This highlights the potential utility of predation risk in lake restoration efforts.

Mechanistic insight into the impact of polystyrene microparticle on submerged plant during asexual propagules germination to seedling: Internalization in functional organs and alterations of physiological phenotypes.

Asexual reproduction is one of the most important propagations in aquatic plants. However, there is a lack of information about the growth-limiting mechanisms induced by microplastics on the submerged plant during asexual propagule germination to seedling. Hence, we investigated the effects of two sizes (2 µm, 0.2 µm) and three concentrations (0.5 mg/L, 5 mg/L, and 50 mg/L) of polystyrene microplastics (PSMPs) on Potamogeton crispus turion germination and seedling growth. Both PSMPs sizes were found in P. crispus seedling tissues. Metabolic profile alterations were observed in leaves, particularly affecting secondary metabolic pathways and ATP-binding cassette transporters. Metal elements are indispensable cofactors for photosynthesis; however, alterations in the metabolic profile led to varying degrees of reduced concentrations in magnesium, iron, copper, and zinc within P. crispus. Therefore, the maximum quantum yield of photosystem II significantly decreased in all concentrations with 0.2 µm-PSMPs, and at 50 mg/L with 2 µm-PSMPs. These findings reveal that internalization of microplastics, nutrient absorption inhibition, and metabolic changes contribute to the negative impact on P. crispus seedlings.

Adaptive responses and transgenerational plasticity of a submerged plant to benthivorous fish disturbance.

Submerged macrophytes play a key role in the restoration of shallow eutrophic lakes. However, in some subtropical lakes, benthivorous fishes dominate the fish assemblages and influence the growth of submerged plants. A comprehensive understanding of the direct and indirect effects of benthivorous fishes on submerged plants is important. We conducted mesocosm experiments to examine the effects of three densities of benthivorous fish, Misgurnus anguillicaudatus, on the water properties, the growth, asexual reproduction, and the germination of turions of Potamogeton crispus L. Our results showed that fish disturbance increased TN, TP, PO4-P, NH4-N, and NO3-N of the water, raising the extinction coefficient K, Chl a, and the periphyton biomass. Benthivorous fish disturbance reduced the total biomass, root length, relative growth rate (RGR), and branching number while increasing the plant height of P. crispus. The P stoichiometric homeostasis coefficient (H P) (except turions) and H N was lower in plant tissues due to fish disturbance. Benthivorous fish disturbances promoted turions formation (e.g., increased turions total numbers and biomass) of P. crispus. Moreover, P. crispus exhibited transgenerational plasticity for benthivorous fish affecting turion emergence. The maximum final germination rate occurred only when fish density in the mother plant grow experiment matched that in the turion germination experiment. Turions generated by P. crispus disturbed by low-density fish exhibited increased germination rates. Our findings suggest that controlling benthivorous fish reduces its indirect and direct effects on submerged vegetation, facilitating the successful restoration of these plants.

Synthesis of Cellulose-Poly(Acrylic Acid) Using Sugarcane Bagasse Extracted Cellulose Fibres for the Removal of Heavy Metal Ions.

In this study, sugarcane bagasse (SCB) was treated with sodium hydroxide and bleached to separate the non-cellulose components to obtain cellulose (CE) fibres. Cross-linked cellulose-poly(sodium acrylic acid) hydrogel (CE-PAANa) was successfully synthesised via simple free-radical graft-polymerisation to remove heavy metal ions. The structure and morphology of the hydrogel display an open interconnected porous structure on the surface of the hydrogel. Various factors influencing batch adsorption capacity, including pH, contact time, and solution concentration, were investigated. The results showed that the adsorption kinetics were in good agreement with the pseudo-second-order kinetic model and that the adsorption isotherms followed the Langmuir model. The maximum adsorption capacities calculated by the Langmuir model are 106.3, 333.3, and 163.9 mg/g for Cu(II), Pb(II), and Cd(II), respectively. Furthermore, X-ray photoelectron spectroscopy (XPS) and energy-dispersive X-ray spectrometry (EDS) results demonstrated that cationic exchange and electrostatic interaction were the main heavy metal ions adsorption mechanisms. These results demonstrate that CE-PAANa graft copolymer sorbents from cellulose-rich SCB can potentially be used for the removal of heavy metal ions.

Association of Diabetes Mellitus with All-Cause and Cause-Specific Mortality among Patients with Metabolic-Dysfunction-Associated Fatty Liver Disease: A Longitudinal Cohort Study.

BACKGROUND: Diabetes mellitus (DM) is a comorbidity commonly presenting with metabolic-dysfunction-associated fatty liver disease (MAFLD); however, few tests for interaction have been reported. Our target was to evaluate the prognostic implications of DM in patients with different forms of MAFLD. METHODS: Using data from the Third National Health and Nutrition Examination Survey (NHANES III) in the United States, we screened 14,797 participants aged 20-74 who received ultrasound examinations from 1988-1994. Among them, 4599 patients met the diagnosis of MAFLD, and we defined mortality as the outcome event. Survival analysis of competitive risk events was performed using Cox regression and sub-distributed risk ratio (SHR). RESULTS: During 21.1 years of follow-up, cardiovascular diseases seemed to be the most common cause of death among MAFLD patients. Of them, DM was present in 25.48% and was independently associated with increased risk of all-cause mortality (HRs: 1.427, 95% CIs: 1.256-1.621, p < 0.001) and cause-specific mortality (cardiovascular-related mortality (HRs: 1.458, 95% CIs: 1.117-1.902, p = 0.005), non-cardiovascular-related mortality (HRs: 1.423, 95% CIs: 1.229-1.647, p < 0.001), and non-cancer-related mortality (HRs: 1.584, 95% CIs: 1.368-1.835, p < 0.001), respectively). Surprisingly, this association was more significant for young patients (p-value for interaction <0.001). Moreover, DM had a greater risk of all-cause and cause-specific mortality among overweight and obese MAFLD patients (p-value for interaction <0.001). CONCLUSIONS: DM increased the risk of all-cause and cause-specific mortality (cardiovascular-related, non-cardiovascular-related, and non-cancer-related) in MAFLD patients, especially in younger patients with excess obesity.

Multidisciplinary nutritional management improves nutritional and hospitalized outcomes of patients with esophageal cancer undergoing chemoradiotherapy: A randomized control trial.

BACKGROUND: This study aimed to investigate the effects of multidisciplinary whole-course nutrition management on the nutritional status and complications during the course of treatment in patients with esophageal cancer (EC) undergoing chemoradiotherapy. METHODS: A total of 36 EC patients undergoing chemoradiotherapy were divided into a control group (n = 18) and an intervention group (n = 18). Participants in the control group were given routine nutritional support, whereas those in the intervention group were provided whole-course nutrition management from the nutrition support team. Nutrition-related indicators, that is, serum albumin level (ALB), hemoglobin (Hb), and C reactive protein were assessed before, during, and after treatment in both groups. The incidence of complications (e.g., lymphocytopenia, radiation esophagitis, and myelosuppression), clinical outcomes, length of hospital stay, and hospital costs were also recorded. Differences between the 2 groups were tested using the Mann-Whitney U and chi-square tests. RESULTS: The ALB and Hb levels of the patients in the control group decreased significantly [ALB: -2.6 (-5.6, 0), P = .01; Hb: -12.0 (-27.0, -2.0), P = .04] and C reactive protein increased [8.9 (2.9, 14.9), P = .02] compared to those before treatment, while the indicators of participants in the intervention group did not change (P > .05). The incidence of grade ≥ II lymphocytopenia was higher in the control group than that in the intervention group (33.3% vs 61.1%, P = .03). Moreover, compared with the control group, the average length of hospital stay decreased by 12 days [47 (40, 50) vs 35 (23, 40), P = .001], and in-patient expenses decreased by 20,504 CNY in the intervention group (P = .004). CONCLUSION: Multidisciplinary whole-course nutrition management can maintain the nutritional status of patients with EC undergoing chemoradiotherapy. This may lower the incidence of complications, shorten hospital stays, and reduce in-patient expenses.

B7-H3 is spliced by SRSF3 in colorectal cancer.

B7-H3, an important co-inhibitor, is abnormally highly expressed in a variety of malignancies. The antibodies targeting B7-H3 have exhibited beneficial therapeutic effects in clinical trials. Therefore, discovery of the regulatory factors in B7-H3 expression may provide new strategies for tumor therapy. Here, we investigated the splicing factors involved in the splicing of B7-H3. By individual knockdown of the splicing factors in colorectal cancer (CRC) cells, we found that B7-H3 expression was markedly inhibited by SRSF3 and SRSF8, especially SRSF3. Then we found that both SRSF3 and B7-H3 were highly expressed in CRC tissues. Moreover, high-expression of either SRSF3 or B7-H3 was significantly correlated with poor prognosis of patients. The expression of B7-H3 mRNA and protein were evidently reduced by SRSF3 silence, but were enhanced by overexpression of SRSF3 in both HCT-116 and HCT-8 cells. The results from the RNA immunoprecipitation (RIP) assays demonstrated that SRSF3 protein directly binds to B7-H3 mRNA. In addition, we constructed a minigene recombinant plasmid for expressing B7-H3 exons 3-6. We found that SRSF3 contributed to the retention of B7-H3 exon 4. These findings demonstrate that SRSF3 involves in the splicing of B7-H3 by directly binding to its exon 4 and/or 6. It may provide novel insights into the regulatory mechanisms of B7-H3 expression and potential strategies for the treatment of CRC.

The Yellow Sea green tide: A risk of macroalgae invasion.

Large scale green tides have bloomed successively in the Yellow Sea since 2007. The floating ecotype of Ulva prolifera, which is responsible for the environmental disaster, drifted a long distance during the blooming time and was exotic to the coastal area. The Yellow Sea green tide can be a potential source to incur bio-invasion. In this study, the distribution pattern and propagule pressure of the floating ecotype was investigated along the Qingdao coastline, which was seriously impacted by the green tide. Two out of 661 attached Ulva specimens collected in different seasons were identified as the floating ecotype by molecular markers, indicating that a few individuals of the floating ecotype had settled down, and their attached population could have spontaneously established. In seawater and sediments, the proportion of the floating ecotype in Ulva propagules reached up to 32% and 69% respectively when the floating algae was accumulating on seashore, which was a great propagule pressure to the local ecosystem. Results of the field test indicated that the available resources and the competition between the floating ecotype and the local Ulva species might be the main restrictions for settlement. Though the current scale of the established population is still small, the risk of biological invasion by the floating ecotype exists and it deserves more attention.

miR-27b inhibits gastric cancer metastasis by targeting NR2F2.

Increasing attention is focused on the down-regulation of miRNAs in cancer process. Nuclear receptor subfamily 2 (NR2F2, also known as COUP-TFII) is involved in the development of many types of cancers, but its role in gastric cancer remains elusive. In this experiment, oncomine and Kaplan-meier database revealed that NR2F2 was up-regulated in gastric cancer and that the high NR2F2 expression contributed to poor survival. MicroRNA-27b was targeted and down-regulated by NR2F2 in human gastric cancer tissues and cells. The ectopic expression of miR-27b inhibited gastric cancer cell proliferation and tumor growth in vitro and in vivo. Assays suggested that the overexpression of miR-27b could promote MGC-803 cells' migration and invasion and retard their metastasis to the liver. In addition, down-regulation of miR-27b enhanced GES-1 cells' proliferation and metastasis in vitro. These findings reveal that miR-27b is a tumor suppressor in gastric cancer and a biomarker for improving patients' survival.

A polymorphism in the promoter region of PD-L1 serves as a binding-site for SP1 and is associated with PD-L1 overexpression and increased occurrence of gastric cancer.

PD-L1 is a member of the B7 family co-inhibitory molecules and plays a critical role in tumor immune escape. In this study, we found a polymorphism rs10815225 in the PD-L1 promoter region was significantly associated with the occurrence of gastric cancer. The GG homozygous frequency was higher in the cancer patients than that in the precancerous lesions, which was higher than that in the health controls. This polymorphism locates in the binding-site of Sp1 transcription factor (SP1). The expression level of PD-L1 mRNA in the GG homozygous cancer patients was apparently higher than that in the GC heterozygotes. Luciferase reporter results showed that SP1 bonded to rs10815225 G-allelic PD-L1 promoter instead of C-allelic. Upregulation and knockdown of SP1 resulted in elevation and attenuation of PD-L1 in SGC-7901 cells, respectively. The chromatin immunoprecipitation results further confirmed the binding of SP1 to the promoter of PD-L1. Additionally, rs10815225 was found to be in disequilibrium with a functional polymorphism rs4143815 in the PD-L1 3'-UTR, and the haplotypes of these two polymorphisms were also markedly related to gastric cancer risk. These results revealed a novel mechanism underlying genetic polymorphisms influencing PD-L1 expression modify gastric cancer susceptibility.

Improving production of thermostable and fluorescent holo-ß-allophycocyanin by metabolically engineered Escherichia coli using response surface methodology.

A stable fluorescent holo-ß-allophycocyanin (holo-ApcB) was produced by metabolically engineered Escherichia coli. The E. coli cells harbored two plasmids for expression of five genes that were involved in the holo-ApcB production. Response surface methodology was employed to investigate the individual and interactive effects of four variables, i.e., initial pH of culture medium, IPTG concentration, post-induction temperature, and induction start time, on holo-ApcB production by E. coli. The experimental results showed that the IPTG concentration, postinduction temperature, and induction start time had significant individual effects on holo-ApcB production. A significant interactive effect was also found between the initial pH of culture and induction start time. The maximum holo-ApcB production of 45.3 mg/L was predicted under the following optimized culture conditions: a postinduction temperature of 28.4°C, initial pH of culture of 7.3, IPTG concentration of 1.1 mM, and postinduction time of 66 min. Holo-ApcB production under the optimized culture conditions increased 5.8-fold, compared with that under the nonoptimized conditions. Response surface methodology proved to be a valuable tool for optimization of holo-ApcB production by metabolically engineered E. coli.

Spatial diversity of bacterioplankton communities in surface water of northern South China Sea.

The South China Sea is one of the largest marginal seas, with relatively frequent passage of eddies and featuring distinct spatial variation in the western tropical Pacific Ocean. Here, we report a phylogenetic study of bacterial community structures in surface seawater of the northern South China Sea (nSCS). Samples collected from 31 sites across large environmental gradients were used to construct clone libraries and yielded 2,443 sequences grouped into 170 OTUs. Phylogenetic analysis revealed 23 bacterial classes with major components α-, ß- and γ-Proteobacteria, as well as Cyanobacteria. At class and genus taxon levels, community structure of coastal waters was distinctively different from that of deep-sea waters and displayed a higher diversity index. Redundancy analyses revealed that bacterial community structures displayed a significant correlation with the water depth of individual sampling sites. Members of α-Proteobacteria were the principal component contributing to the differences of the clone libraries. Furthermore, the bacterial communities exhibited heterogeneity within zones of upwelling and anticyclonic eddies. Our results suggested that surface bacterial communities in nSCS had two-level patterns of spatial distribution structured by ecological types (coastal VS. oceanic zones) and mesoscale physical processes, and also provided evidence for bacterial phylogenetic phyla shaped by ecological preferences.

A functional variant at miR-132-3p, miR-212-3p, and miR-361-5p binding site in CD80 gene alters susceptibility to gastric cancer in a Chinese Han population.

A number of single-nucleotide polymorphisms within the 3'-UTR of genes have been shown to relate to the occurrence of cancers. In this study, by using polymerase chain reaction-restriction fragment length analysis method, we determined an SNP rs1599795 in the 3'-UTR of CD80 gene in 183 gastric cancer patients and 348 healthy controls. Statistical analysis results showed that SNP rs1599795 genotypes were significantly correlated with the risk of gastric cancer. Compared with the AA homozygotes, the TA heterozygotes were significantly more prevalent in the patients (OR 1.44, 95 % CI 0.98-2.11) with a larger tumor size (P = 0.001), deeper infiltration (P = 1.5 × 10(-5)), higher possibility of lymph node metastasis (P = 0.003), and more in the late stage (TNM stage III and IV; P = 0.003); the TT homozygotes had larger tumor size (P = 0.001) and lower degree of differentiation (P = 2.2 × 10(-4)). Dual-luciferase reporter assays showed that miR-132-3p, miR-212-3p, and miR-361-5p inhibited the expression of CD80 through binding with the CD80 3'-UTR, and this inhibitory role of miR-132-3p, miR-212-3p, and miR-361-5p was impacted by rs1599795. Our findings have shown that the SNP rs1599795 in CD80 3'-UTR, through disrupting the regulatory role of miR-132-3p, miR-212-3p, and miR-361-5p in CD80 expression, contributed to the occurrence of gastric cancer.

Impacts of mariculture on the diversity of bacterial communities within intertidal sediments in the Northeast of China.

Mariculture is one of the major seafood supplies worldwide and has caused serious environmental concerns on the coastal zone. Its rapid development has been shown to disrupt the sediment ecosystems and thus influence the benthic bacterial communities. Bacterial diversity and community structure within both adjacent farms and non-cultured zones intertidal sediments along the coasts of Qinhuangdao and Dalian, China, were investigated using full-length 16S rRNA gene-based T-RFLP analyses and clone library construction. Richness and Shannon-Wiener index were significantly increased at sites adjacent the mariculture farm with mean values of 29 and 2.97 from peak profiles of T-RFLP result. Clustering analyses suggested that impacts of mariculture on bacterial diversity of sediment were significantly larger than those resulted from temporal and spatial scales. Upon comparisons of RFLP patterns from 602 clones from libraries of the selected five samples, 137 OTUs were retrieved. Members of γ- and δ-Proteobacteria, Bacilli, Flavobacteria, and Actinobacteria were recorded in all libraries. In addition, γ-Proteobacteria were dominant in all samples (21.7~45.0 %). Redundancy analysis revealed that the distribution of bacterial composition seemed to be determined by the variables of salinity, PO4 (3-)-P, NH4 (+)-N, and Chlorophyll a content. The phyla of γ-Proteobacteria, Clostridia, Flavobacteria, Bacilli, and Planctomycetes were principal components to contribute to the bacterial differences of clone libraries. Our finding demonstrated that these phyla could display variations of bacterial composition linked to environmental disturbance resulted from mariculture.

Biosynthesis of a stable allophycocyanin beta subunit in metabolically engineered Escherichia coli.

Allophycocyanin (APC) is widely used as a fluorescent tag for fluorescence detection techniques. In this study, the apcB gene from a thermophilic cyanobacterium strain was cloned and ligated into an expression vector to construct a pathway for the biosynthesis of an allophycocyanin beta subunit (holo-apcBT) in Escherichia coli. Isopropyl ß-d-1-thiogalactopyranoside induction successfully reconstituted holo-apcBT in E. coli. The recombinant holo-apcB showed spectroscopic properties similar to native APC. The stability and spectroscopic properties of this protein were then compared with another recombinant allophycocyanin beta subunit (holo-apcBM) whose apcB gene was cloned from mesophilic cyanobacterium. At high temperatures and during the course of storage, holo-apcBT was significantly more stable than holo-apcBM. In addition, holo-apcBT had an unexpectedly higher extinction coefficient and fluorescence quantum yield than holo-apcBM, suggesting that holo-apcBT would be a promising fluorescent tag and serve as a substitute for native APC.

Genomic sequence-based discovery of novel angucyclinone antibiotics from marine Streptomyces sp. W007.

A large number of novel bioactive compounds were discovered from microbial secondary metabolites based on the traditional bioactivity screenings. Recent fermentation studies indicated that the crude extract of marine Streptomyces sp. W007 possessed great potential in agricultural fungal disease control against Phomopsis asparagi, Polystigma deformans, Cladosporium cucumerinum, Monilinia fructicola, and Colletotrichum lagenarium. To further evaluate the biosynthetic potential of secondary metabolites, we sequenced the genome of Streptomyces sp. W007 and analyzed the identifiable secondary metabolite gene clusters. Moreover, one gene cluster with type II PKS implied the possibility of Streptomyces sp. W007 to produce aromatic polyketide of angucyclinone antibiotics. Therefore, two novel compounds, 3-hydroxy-1-keto-3-methyl-8-methoxy-1,2,3,4-tetrahydro-benz[α]anthracene and kiamycin with potent cytotoxicities against human cancer cell lines, were isolated from the culture broth of Streptomyces sp. W007. In addition, other four known angucyclinone antibiotics were obtained. The gene cluster for these angucyclinone antibiotics could be assigned to 20 genes. This work provides powerful evidence for the interplay between genomic analysis and traditional natural product isolation research.

Draft genome sequence of marine Streptomyces sp. strain W007, which produces angucyclinone antibiotics with a benz[a]anthracene skeleton.

A series of angucyclinone antibiotics have been isolated from marine Streptomyces sp. strain W007 and identified. Here, a draft genome sequence of Streptomyces sp. W007 is presented. The genome contains an intact biosynthetic gene cluster for angucyclinone antibiotics, which provides insight into the combinatorial biosynthesis of angucyclinone antibiotics produced by marine streptomycetes.