Super-enhancer-associated EEPD1 facilitates EMT-mediated metastasis by regulating the PI3K/AKT/mTOR pathway in gastric cancer.

This study focused on exploring the mechanism of the EMT mediated by endonuclease/exonuclease/phosphatase family domain-containing 1 (EEPD1) in gastric cancer metastasis. Through bioinformatics analysis, EEPD1 was found to be a target gene of super enhancers (SEs) in gastric cancer tissues. EEPD1 exhibited higher expression levels in tumor tissues and was associated with poor prognosis. In vitro and in vivo studies have demonstrated that silencing EEPD1 significantly suppressed the proliferation, metastasis, and invasion of gastric cancer cells. Furthermore, EEPD1 knockdown was involved in the regulation of the EMT and suppressed expression of AKT, a downstream component of the PI3K pathway, leading to a reduction in the phosphorylation levels of AKT and its downstream molecule, mTOR. These results showed the potential of EEPD1 as a prognostic indicator and therapeutic target in gastric cancer.

Nanoreactor of Fe, N Co-Doped Hollow Carbon Spheres for Oxygen Reduction Catalysis.

A simple template strategy was applied to prepare a Fe, N co-doped hollow carbon (Fe-NHC) nanoreactor for the oxygen reduction reaction (ORR) by coating Fe nanoparticles (Fe-NPs) with polydopamine (PDA), followed by high temperature pyrolysis and acid-leaching. With this method, Fe-NPs were used as both the template and the metal precursor, so that the nanoreactors can preserve the original spherical morphology and embed Fe single atoms on the inner walls. The carbonized PDA contained abundant N content, offering an ideal coordination environment for Fe atoms. By regulating the mass ratio of Fe-NPs and PDA, an optimal sample with a carbon layer thickness of 12 nm (Fe-NHC-3) was obtained. The hollow spherical structure of the nanoreactors and the atomically dispersed Fe were verified by various physical characterizations. As a result, Fe-NHC-3 performed well in ORR tests under alkaline conditions, with high catalytic activity, durability, and methanol resistance, demonstrating that the as-fabricated materials have the potential to be applied in the cathodic catalysis of fuel cells.

Copper-based metal-organic framework impedes triple-negative breast cancer metastasis via local estrogen deprivation and platelets blockade.

Metastasis is one of the main causes of failure in the treatment of triple-negative breast cancer (TNBC). Abnormally estrogen level and activated platelets are the key driving forces for TNBC metastasis. Herein, an "ion/gas" bioactive nanogenerator (termed as IGBN), comprising a copper-based MOF and loaded cisplatin-arginine (Pt-Arg) prodrug is developed for metastasis-promoting tumor microenvironment reprogramming and TNBC therapy. The copper-based MOF not only serves as a drug carrier, but also specifically produces Cu2+ in tumors, which catalytic oxidizing estrogen to reduce estrogen levels in situ. Meanwhile, the rationally designed Pt-Arg prodrug reduced into cisplatin to significantly promote the generation of H2O2 in the tumor, then permitting self-augmented cascade NO gas generation by oxidizing Arg through a H2O2 self-supplied way, thus blocking platelet activation in tumor. We clarified that IGBN inhibited TNBC metastasis through local estrogen deprivation and platelets blockade, affording 88.4% inhibition of pulmonary metastasis in a 4T1 mammary adenocarcinoma model. Notably, the locally copper ion interference, NO gas therapy and cisplatin chemotherapy together resulted in an enhanced therapeutic efficacy in primary tumor ablation without significant toxicity. This "ion/gas" bioactive nanogenerator offers a robust and safe strategy for TNBC therapy.

In vitro transcriptomes analysis identifies some special genes involved in pathogenicity difference of the Beauveria bassiana against different insect hosts.

Typical entomopathogenic filamentous fungi such as Beauveria bassiana infect susceptible hosts via penetration of insect cuticle. The pathogenicity of B. bassiana strain to diverse insect hosts is different. While the molecular mechanisms of B. bassiana adapt to different insects are not well clear. B. bassiana GXsk1011 is a hyper-virulent strain from silkworm, which was investigated on the metabolic responses to three cuticle extracts of Bombyx mori, Helicoverpa armigera and Clanis bilineata at 24 h by RNA-seq method. A total of 638 up- and 400 down-regulated differentially expressed genes (DEGs) were identified in B. bassiana grown on H. armigera compared with B. mori, and 910 up- and 401 down-regulated genes for C. bilineata compared with B. mori. Functional categorization showed that DEGs are mainly involved in metabolic processes, localization, catalytic activity and transporter activity. Analysis of 20 highest fold change genes in DEGs showed that when B. bassiana transferred to non-original hosts as H. armigera and C. bilineata, the adhesion (Mad1), protease (Pr2) and cell surface protein (BBA_09174), etc. were down-regulated. While the class III chitinase ChiA2 (BBA_05353, Bbchi-17), major allergen Asp f 2-like protein (BBA_05395, Bb-f2) and nonribosomal peptide synthase, etc. were up-regulated. The secretory lipase that responded to H. armigera and the phosphate permease responded to C. bilineata were also up-regulated in the Top 20 DEGs. These special expressed genes indicate when the B. bassiana transferred to non-original hosts (or called as non-natural hosts), the strain appeared the changes of metabolic response and infection strategies to adapt to new hosts, and implied the key actions of infected adaptation were to break the barrier of different cuticle chitin component and against the immune stress of hosts. This study provided an insight into the B. bassiana that with wide host ranges how to adapt to infect different insect hosts, which will help us to further understand the pathogenesis of B. bassiana infection.

Statin use and the overall survival of renal cell carcinoma: A meta-analysis.

PURPOSE: Statins are commonly prescribed drugs that reduce cholesterol levels and the risk of cardiovascular and cerebrovascular events. Clinical studies have shown that statins also possess cancer-preventive properties. Two studies have reported that statins also possess cancer-preventive properties; however, whether statins improve the prognosis of patients with renal cell carcinoma is still unclear. In this study, we used meta-analysis to evaluate the association between statin use and overall survival risk in patients with renal cell carcinoma. METHODS: Published studies on statin-treated renal cell carcinoma were retrieved from PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure and Wanfang databases from inception to July 2019. The relevant data were extracted and a meta-analysis was performed using Cochrane Review Manager (RevMan 5.3) software. RESULTS: Data from five studies, which reported on 5,299 patients, were analysed. The application of statins showed no effects on the overall survival of patients with renal cell carcinoma compared with the control group (OR = 1.07, 95% CI:0.77 to 1.49, P = 0.68). CONCLUSIONS: The findings of this meta-analysis suggest that statin application does not affect the overall survival of patients with renal cell carcinoma.

Serum sclerostin and adverse outcomes in elderly patients with stable coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Recently, sclerostin, a bone-derived protein, has been shown to play a key role in atherosclerosis progression. However, few studies have investigated the influence of sclerostin on cardiovascular disease prognosis. We investigated the relationship between serum sclerostin levels and adverse outcomes in elderly patients with stable coronary artery disease (SCAD) who were undergoing percutaneous coronary intervention (PCI). METHODS: We enrolled 310 elderly SCAD patients who underwent PCI in this study and followed them 3 years. According to the median serum sclerostin levels, subjects were stratified into a low sclerostin (low scl) group (n = 144) and a high sclerostin (high scl) group (n = 166). Time-to-event analyses were performed with the Kaplan-Meier method. Associations between sclerostin levels and main adverse cardiovascular and cerebrovascular events (MACCEs) and mortality were evaluated by Cox multivariate regression analysis. The prognostic power of predictive models was verified by the concordance index and receiver operating characteristic curve analysis. RESULTS: The high scl group had a significantly higher MACCE-free rate and better survival than the low scl group. Serum sclerostin was an independent predictor and could improve the prognostic power for adverse outcomes. In addition, serum sclerostin levels were significantly associated with bone turnover markers, a lower presence of multivessel disease and a lower CCS angina class. CONCLUSIONS: Serum sclerostin is a prognostic parameter for predicting and intervening in the adverse outcomes of elderly SCAD patients undergoing PCI, which may be explained by its potential role in the bone-vascular axis.

Glucose-Induced Trophic Shift in an Endosymbiont Dinoflagellate with Physiological and Molecular Consequences.

Interactions between the dinoflagellate endosymbiont Symbiodinium and its cnidarian hosts (e.g. corals, sea anemones) are the foundation of coral-reef ecosystems. Carbon flow between the partners is a hallmark of this mutualism, but the mechanisms governing this flow and its impact on symbiosis remain poorly understood. We showed previously that although Symbiodinium strain SSB01 can grow photoautotrophically, it can grow mixotrophically or heterotrophically when supplied with Glc, a metabolite normally transferred from the alga to its host. Here we show that Glc supplementation of SSB01 cultures causes a loss of pigmentation and photosynthetic activity, disorganization of thylakoid membranes, accumulation of lipid bodies, and alterations of cell-surface morphology. We used global transcriptome analyses to determine if these physiological changes were correlated with changes in gene expression. Glc-supplemented cells exhibited a marked reduction in levels of plastid transcripts encoding photosynthetic proteins, although most nuclear-encoded transcripts (including those for proteins involved in lipid synthesis and formation of the extracellular matrix) exhibited little change in their abundances. However, the altered carbon metabolism in Glc-supplemented cells was correlated with modest alterations (approximately 2x) in the levels of some nuclear-encoded transcripts for sugar transporters. Finally, Glc-bleached SSB01 cells appeared unable to efficiently populate anemone larvae. Together, these results suggest links between energy metabolism and cellular physiology, morphology, and symbiotic interactions. However, the results also show that in contrast to many other organisms, Symbiodinium can undergo dramatic physiological changes that are not reflected by major changes in the abundances of nuclear-encoded transcripts and thus presumably reflect posttranscriptional regulatory processes.

Characterization of a Lipase From the Silkworm Intestinal Bacterium Bacillus pumilus With Antiviral Activity Against Bombyx mori (Lepidoptera: Bombycidae) Nucleopolyhedrovirus In Vitro.

To investigate whether Bombyx mori Linnaeus (Lepidoptera: Bombycidae) intestinal microorganism play a role in the host defence system against viral pathogens, a lipase gene from the silkworm intestinal bacterium Bacillus pumilus SW41 was characterized, and antiviral activity of its protein against B. mori nucleopolyhedrovirus (BmNPV) was tested. The lipase gene has an open-reading frame of 648 bp, which encodes a 215-amino-acid enzyme with a 34-amino-acid signal peptide. The recombinant lipase (without signal peptide) was expressed and purified by using an Escherichia coli BL21 (DE3) expression system. The total enzyme activity of this recombinant lipase reached 277.40 U/mg at the optimum temperature of 25°C and optimum pH value of 8.0. The antiviral test showed that a relative high concentration of the recombinant lipase reduced BmNPV infectivity in vitro, which resulted in decreased viral DNA abundance and viral occlusion bodies. Besides, the preincubation method also suggested that the lipase probably directly acting on the budded virions. The results suggest that the lipase from intestinal bacterium B. pumilus SW41 is a potential antiviral factor for silkworm against BmNPV.

Transcriptomic analysis of two Beauveria bassiana strains grown on cuticle extracts of the silkworm uncovers their different metabolic response at early infection stage.

Beauveria bassiana is an important entomopathogenic fungus which not only widely distributes in the environment but also shows phenotypic diversity. However, the mechanism of pathogenic differences among natural B. bassiana strains has not been revealed at transcriptome-wide level. In the present study, in order to explore the mechanism, two B. bassiana strains with different pathogenicity were isolated from silkworms (Bombyx mori L.) and selected to analyze the gene expression of early stage by culturing on cuticle extracts of the silkworm and using RNA-sequencing technique. A total of 2108 up-regulated and 1115 down-regulated genes were identified in B. bassiana strain GXsk1011 (hyper-virulent strain) compared with B. bassiana strain GXtr1009 (hypo-virulent strain), respectively. The function categorization of differential expressed genes (DEGs) showed that most of them involved in metabolic process, biosynthesis of secondary metabolites, catalytic activity, and some involved in nutrition uptake, adhesion and host defense were also noted. Based on our data, distinct pathogenicity among different strains of B. bassiana may largely attribute to unique gene expression pattern which differed at very early infection process. Most of the genes involved in conidia adhesion, cuticle degradation and fungal growth were up-regulated in hyper-virulent B. bassiana strain GXsk1011. Furthermore, in combination with fungal growth analysis, our research provided a clue that fungal growth may also play an important role during early infection process. The results will help to explain why different B. bassiana strains show distinct pathogenicity on the same host even under same condition. Moreover, the transcriptome data were also useful for screening potential virulence factors.

Symbiodinium transcriptome and global responses of cells to immediate changes in light intensity when grown under autotrophic or mixotrophic conditions.

Symbiosis between unicellular dinoflagellates (genus Symbiodinium) and their cnidarian hosts (e.g. corals, sea anemones) is the foundation of coral reef ecosystems. Dysfunction of this symbiosis under changing environmental conditions has led to global reef decline. Little information is known about Symbiodinium gene expression and mechanisms by which light impacts host-symbiont associations. To address these issues, we generated a transcriptome from axenic Symbiodinium strain SSB01. Here we report features of the transcriptome, including occurrence and length distribution of spliced leader sequences, the functional landscape of encoded proteins and the impact of light on gene expression. Expression of many Symbiodinium genes appears to be significantly impacted by light. Transcript encoding cryptochrome 2 declined in high light while some transcripts for Regulators of Chromatin Condensation (RCC1) declined in the dark. We also identified a transcript encoding a light harvesting AcpPC protein with homology to Chlamydomonas LHCSR2. The level of this transcript increased in high light autotrophic conditions, suggesting that it is involved in photo-protection and the dissipation of excess absorbed light energy. The most extensive changes in transcript abundances occurred when the algae were transferred from low light to darkness. Interestingly, transcripts encoding several cell adhesion proteins rapidly declined following movement of cultures to the dark, which correlated with a dramatic change in cell surface morphology, likely reflecting the complexity of the extracellular matrix. Thus, light-sensitive cell adhesion proteins may play a role in establishing surface architecture, which may in turn alter interactions between the endosymbiont and its host.

Antiviral activity and specific modes of action of bacterial prodigiosin against Bombyx mori nucleopolyhedrovirus in vitro.

Prodigiosin, the tripyrrole red pigment, is a bacterial secondary metabolite with multiple bioactivities; however, the antiviral activity has not been reported yet. In the present study, we found the antiviral activity of bacterial prodigiosin on Bombyx mori nucleopolyhedrovirus (BmNPV)-infected cells in vitro, with specific modes of action. Prodigiosin at nontoxic concentrations selectively killed virus-infected cells, inhibited viral gene transcription, especially viral early gene ie-1, and prevented virus-mediated membrane fusion. Under prodigiosin treatment, both progeny virus production and viral DNA replication were significantly inhibited. Fluorescent assays showed that prodigiosin predominantly located in cytoplasm which suggested it might interact with cytoplasm factors to inhibit virus replication. In conclusion, the present study clearly indicates that prodigiosin possesses significant antiviral activity against BmNPV.

The red pigment prodigiosin is not an essential virulence factor in entomopathogenic Serratia marcescens.

Although pigments produced by pathogenic microbes are generally hypothesized as essential virulence factors, the role of red pigment prodigiosin in the pathogenesis of entomopathogenic Serratia marcescens is not clear. In this study, we analyzed the pathogenicity of different pigmented S. marcescens strains and their non-pigmented mutants in silkworms. Each pigmented strain and the corresponding non-pigmented mutants showed very similar LD50 value (statistically no difference), but caused very different symptom (color of the dead larva). Our results clearly indicated that the red pigment prodigiosin is not an essential virulence factor in entomopathogenic S. marcescens.

Spatial distribution and variability of carbon storage in different sympodial bamboo species in China.

Selection of tree species is potentially an important management decision for increasing carbon storage in forest ecosystems. This study investigated and compared spatial distribution and variability of carbon storage in 8 sympodial bamboo species in China. The results of this study showed that average carbon densities (CDs) in the different organs decreased in the order: culms (0.4754 g g(-1)) > below-ground (0.4701 g g(-1)) > branches (0.4662 g g(-1)) > leaves (0.4420 g g(-1)). Spatial distribution of carbon storage (CS) on an area basis in the biomass of 8 sympodial bamboo species was in the order: culms (17.4-77.1%) > below-ground (10.6-71.7%) > branches (3.8-11.6%) > leaves (0.9-5.1%). Total CSs in the sympodial bamboo ecosystems ranged from 103.6 Mg C ha(-1) in Bambusa textilis McClure stand to 194.2 Mg C ha(-1) in Dendrocalamus giganteus Munro stand. Spatial distribution of CSs in 8 sympodial bamboo ecosystems decreased in the order: soil (68.0-83.5%) > vegetation (16.8-31.1%) > litter (0.3-1.7%). Total current CS and biomass carbon sequestration rate in the sympodial bamboo stands studied in China is 93.184 × 10(6) Mg C ha(-1) and 8.573 × 10(6) Mg C yr(-1), respectively. The sympodial bamboos had a greater CSs and higher carbon sequestration rates relative to other bamboo species. Sympodial bamboos can play an important role in improving climate and economy in the widely cultivated areas of the world.

Genome-wide distribution of 5-hydroxymethyluracil and chromatin accessibility in the Breviolum minutum genome.

BACKGROUND: In dinoflagellates, a unique and extremely divergent genomic and nuclear organization has evolved. The highly unusual features of dinoflagellate nuclei and genomes include permanently condensed liquid crystalline chromosomes, primarily packaged by proteins other than histones, genes organized in very long unidirectional gene arrays, a general absence of transcriptional regulation, high abundance of the otherwise very rare DNA modification 5-hydroxymethyluracil (5-hmU), and many others. While most of these fascinating properties are originally identified in the 1970s and 1980s, they have not yet been investigated using modern genomic tools. RESULTS: In this work, we address some of the outstanding questions regarding dinoflagellate genome organization by mapping the genome-wide distribution of 5-hmU (using both immunoprecipitation-based and basepair-resolution chemical mapping approaches) and of chromatin accessibility in the genome of the Symbiodiniaceae dinoflagellate Breviolum minutum. We find that the 5-hmU modification is preferentially enriched over certain classes of repetitive elements, often coincides with the boundaries between gene arrays, and is generally correlated with decreased chromatin accessibility, the latter otherwise being largely uniform along the genome. We discuss the potential roles of 5-hmU in the functional organization of dinoflagellate genomes and its relationship to the transcriptional landscape of gene arrays. CONCLUSIONS: Our results provide the first window into the 5-hmU and chromatin accessibility landscapes in dinoflagellates.

Enhancing activity and stability of FeNC catalysts through co incorporation for oxygen reduction reaction.

FeNC single atom catalysts (SACs) have attracted great interest due to their highly active FeN4 sites. However, the pyrolysis treatment often leads to inevitable metal migration and aggregation, which reduces the catalytic activity. Moreover, due to the Fenton reaction caused by FeNC in alkaline and acidic solutions, the presence of Fe and peroxide in electrodes may generate free radicals, resulting in serious degradation of the organic ionomer and the membrane. Herein, we report an original strategy of introducing Co single atoms into FeNC catalysts, forming atomically dispersed bimetallic active sites (FeCoNC) and improving the activity and stability of the catalyst. Benefiting from this strategy, FeCoNC catalyst exhibits excellent oxygen reduction reaction (ORR) activity in alkaline media (E1/2 = 0.88 V) and in acidic media (E1/2 = 0.77 V). As the cathode of Zn-air battery (ZAB), FeCoNC shows an excellent peak power density of 142.8 mW cm-2 and a specific capacity of 806.6 mAh/gZn. This work provides a novel avenue to optimize and enhance the ORR performance of atomic dispersed FeNC catalysts.

Biosynthesis of chlorophyll c in a dinoflagellate and heterologous production in planta.

Chlorophyll c is a key photosynthetic pigment that has been used historically to classify eukaryotic algae. Despite its importance in global photosynthetic productivity, the pathway for its biosynthesis has remained elusive. Here we define the CHLOROPHYLL C SYNTHASE (CHLCS) discovered through investigation of a dinoflagellate mutant deficient in chlorophyll c. CHLCSs are proteins with chlorophyll a/b binding and 2-oxoglutarate-Fe(II) dioxygenase (2OGD) domains found in peridinin-containing dinoflagellates; other chlorophyll c-containing algae utilize enzymes with only the 2OGD domain or an unknown synthase to produce chlorophyll c. 2OGD-containing synthases across dinoflagellate, diatom, cryptophyte, and haptophyte lineages form a monophyletic group, 8 members of which were also shown to produce chlorophyll c. Chlorophyll c1 to c2 ratios in marine algae are dictated in part by chlorophyll c synthases. CHLCS heterologously expressed in planta results in the accumulation of chlorophyll c1 and c2, demonstrating a path to augment plant pigment composition with algal counterparts.

Protocol for the generation of Symbiodiniaceae mutants using UV mutagenesis.

Genetic approaches are limited in the dinoflagellate family, Symbiodiniaceae, causing a bottleneck in the discovery of useful mutants toward the goal of preventing future coral bleaching events. In this protocol, we demonstrate the application of UV exposure, coupled with downstream phenotypic screening and mutant isolation, to form a UV mutagenesis pipeline. This pipeline provides an avenue to generate Symbiodiniaceae mutants to help link genotype to phenotype, as well as address previously unanswered questions surrounding relationships with host organisms, like coral. For complete details on the use and execution of this protocol, please refer to Jinkerson et al. (2022).1.

Genome-wide distribution of 5-hydroxymethyluracil and chromatin accessibility in the Breviolum minutum genome.

In dinoflagellates, a unique and extremely divergent genomic and nuclear organization has evolved. The highly unusual features of dinoflagellate nuclei and genomes include permanently condensed liquid crystalline chromosomes, primarily packaged by proteins other than histones, genes organized in very long unidirectional gene arrays, a general absence of transcriptional regulation, high abundance of the otherwise very rare DNA modification 5-hydroxymethyluracil (5-hmU), and many others. While most of these fascinating properties were originally identified in the 1970s and 1980s, they have not yet been investigated using modern genomic tools. In this work, we address some of the outstanding questions regarding dinoflagellate genome organization by mapping the genome-wide distribution of 5-hmU (using both immunoprecipitation-based and basepair-resolution chemical mapping approaches) and of chromatin accessibility in the genome of the Symbiodiniaceae dinoflagellate Breviolum minutum. We find that the 5-hmU modification is preferentially enriched over certain classes of repetitive elements, often coincides with the boundaries between gene arrays, and is generally correlated with decreased chromatin accessibility, the latter otherwise being largely uniform along the genome. We discuss the potential roles of 5-hmU in the functional organization of dinoflagellate genomes and its relationship to the transcriptional landscape of gene arrays.

Microplastics stimulated nitrous oxide emissions primarily through denitrification: A meta-analysis.

Microplastics can profoundly alter nitrogen cycling. However, it remains poorly understood how microplastics impact soil nitrogen processes and generate N2O. A meta-analysis was conducted for this investigation based on 60 published studies to elucidate the effects of microplastics on soil nitrogen cycling, from genes to processes. Under microplastic exposure, the emissions of soil N2O was significantly increased (140.6%), while the nitrate reductase activities increased by 4.8%. The denitrification rate and number of denitrifier genes were increased by 17.8% and 10.6%, respectively. Meanwhile, the nitrification rate and nitrifier genes were not significantly altered, so did the nitrogen immobilization and mineralization rates. The additional emission of soil N2O might primarily from stimulated denitrification. Soil N2O emission and denitrification genes were always increased, regardless of the concentrations of microplastic or experiment duration. As a result, the nitrite was increased by 38.8% and nitrate was decreased by 22.4%, respectively. Interestingly, the N2O emission increments and copy number of denitrifiers genes diminished over time. This study revealed divergent changes in soil nitrogen processes and highlighted N2O emissions with a greater denitrification rate under microplastic exposure. The negative impacts of microplastics on soil health were revealed from the perspective of soil nitrogen availability and N2O emissions.