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Sepsis is a life-threatening condition caused by an excessive inflammatory response to an infection. However, the precise regulatory mechanism of sepsis remains unclear. Using a strand-specific RNA-sequencing, we identified 115 hub differentially expressed long noncoding RNAs (lncRNAs) and 443 mRNAs in septic patients, primarily participated in crucial pathways including neutrophil extracellular trap (NET) formation and toll-like receptor signaling. Notably, NETs related gene aquaporin-9 (AQP9) and its associated lncRNAs exhibited significant upregulation in septic neutrophils. Functional experiments revealed AQP9 interacts with its lncRNAs to augment the formation of neutrophil NETs. In murine sepsis models, AQP9 inhibition with phloretin reduced proinflammatory cytokine production and lung damage. These findings provide crucial insights into the regulatory role of AQP9 in sepsis, unraveling its interaction with associated lncRNAs in transmitting downstream signals, holding promise in informing the development of novel therapeutic strategies aimed at ameliorating the debilitating effects of sepsis.
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Aquaporinas , Armadilhas Extracelulares , Neutrófilos , RNA Longo não Codificante , RNA Mensageiro , Sepse , Sepse/imunologia , Sepse/genética , Sepse/metabolismo , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/imunologia , Humanos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Neutrófilos/imunologia , Camundongos , Masculino , Aquaporinas/genética , Aquaporinas/metabolismo , Camundongos Endogâmicos C57BL , Citocinas/metabolismo , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Transdução de SinaisRESUMO
Thioesters make up an important class of bioactive compounds. Due to their chemoselectivity, they have been widely used in the synthesis of a wide range of complex bioactive molecules and natural products. At present, chemists have developed a variety of methods for the preparation of thioester compounds. However, these methods usually require the use of transition metal catalysis or harsh reaction conditions. The strategy of synthesizing thioester compounds via visible light-induced electron donor-acceptor (EDA) complex reactions avoids the problems associated with conventional methods through the development of photocatalysis. Here we report a sustainable method for thiocarbonylating aryl sulfonium salts via a visible light-induced EDA complex process without transition metals.
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Light irradiation of stilbene supramolecular polymers produces [2+2] cycloadducts in the kinetically trapped state, which convert to the thermodynamically favorable state upon thermal annealing due to the shift of hydrogen bonds from intra- to inter-complexation modes.
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Lung cancer is one of the most prevalent human cancers with a high lethality rate worldwide. In this study, we demonstrated that GSE1 (genetic suppressor element 1) expression is aberrantly upregulated in lung adenocarcinoma and that GSE1 depletion inhibits the proliferation and migration of both A549 and H1299 cells. Immunoprecipitation assays demonstrated that GSE1 interacts with histone deacetylase 1 (HDAC1) and other BRAF-HDAC complex (BHC) components in cells. The transcriptome of GSE1-knockdown A549 cells indicated that 207 genes were upregulated and 159 were downregulated based on a p-value < .05 and fold change ≥ 1.5. Bioinformatics analysis suggested that 140 differentially expressed genes harbor binding sites for HDAC1, including the tumor suppressor gene KLF6 (Kruppel-like factor 6). Indeed, quantitative reverse-transcription polymerase chain reaction and western blot analysis revealed that GSE1 could inhibit the transcription of KLF6 in lung cancer cells. In conclusion, GSE1 cooperates with HDAC1 to promote the proliferation and metastasis of non-small cell lung cancer cells through the downregulation of KLF6 expression.
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Endoplasmic reticulum stress (ERS) is commonly induced by accumulating misfolded or unfolded proteins in tumor microenvironment. Long non-coding RNAs (lncRNAs) play important roles in ERS response and lung adenocarcinoma (LUAD) progression. However, the role of ERS-related lncRNAs in LUAD remains unknown. In this study, we aimed to identify ERS-associated lncRNAs with prognostic value in LUAD and characterize their clinical implications. Cox and least absolute shrinkage and selection operator regression analyses identified nine ERS-related lncRNAs with independent prognostic abilities, including five protective factors (CROCCP2, KIAA0125, LINC0996, RPARP-AS1 and TBX5-AS1) and four risk factors (LINC0857, LINC116, RP11-21L23.2 and RP11-295G20.2). We developed an ERS-related lncRNA risk prediction model in predicting overall survival of LUAD patients, which classified TCGA cohorts into high-risk (HS) and low-risk (LS) groups. Comprehensive bioinformatic analyses revealed HS patients featured with late-stage tumors, greater mutation burdens, weaker anti-tumor immunity/responses, and lower sensitivity to targeted drugs compared to LS patients, contributing to tumor progression and a poor prognosis. Functional enrichment analysis implicated these ERS-related lncRNAs in cell migration, cell death, and immunity. Furthermore, expression of the most significantly upregulated risk lncRNA, RP11-295G20.2, was validated at the mRNA level using clinical LUAD samples. Knockdown of RP11-295G20.2 obviously reduced ERS and suppressed proliferation, invasion, and migration of LUAD cells. This novel ERS-related lncRNA signature provides a new biomarker for prognostic prediction, and ERS-associated RP11-295G20.2 serves as a potential therapeutic target in LUAD.
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Adenocarcinoma de Pulmão , Estresse do Retículo Endoplasmático , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/mortalidade , Estresse do Retículo Endoplasmático/genética , Prognóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Masculino , Feminino , Biomarcadores Tumorais/genética , Técnicas de Silenciamento de Genes , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Sepsis is a life-threatening condition caused by an excessive inflammatory response to an infection, associated with high mortality. However, the regulatory mechanism of sepsis remains unclear. RESULTS: In this study, bioinformatics analysis revealed the novel key biomarkers associated with sepsis and potential regulators. Three public datasets (GSE28750, GSE57065 and GSE95233) were employed to recognize the differentially expressed genes (DEGs). Taking the intersection of DEGs from these three datasets, GO and KEGG pathway enrichment analysis revealed 537 shared DEGs and their biological functions and pathways. These genes were mainly enriched in T cell activation, differentiation, lymphocyte differentiation, mononuclear cell differentiation, and regulation of T cell activation based on GO analysis. Further, pathway enrichment analysis revealed that these DEGs were significantly enriched in Th1, Th2 and Th17 cell differentiation. Additionally, five hub immune-related genes (CD3E, HLA-DRA, IL2RB, ITK and LAT) were identified from the protein-protein interaction network, and sepsis patients with higher expression of hub genes had a better prognosis. Besides, 14 drugs targeting these five hub related genes were revealed on the basis of the DrugBank database, which proved advantageous for treating immune-related diseases. CONCLUSIONS: These results strengthen the new understanding of sepsis development and provide a fresh perspective into discriminating the candidate biomarkers for predicting sepsis as well as identifying new drugs for treating sepsis.
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Perfilação da Expressão Gênica , Sepse , Humanos , Perfilação da Expressão Gênica/métodos , Biomarcadores , Mapas de Interação de Proteínas/genética , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/genética , Biologia Computacional/métodos , Redes Reguladoras de GenesRESUMO
[This corrects the article DOI: 10.1039/C7SC03351F.].
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Avoiding the low specificity of phototheranostic reagents at the tumor site is a major challenge in cancer phototherapy. Meanwhile, angiogenesis in the tumor is not only the premise of tumor occurrence but also the basis of tumor growth, invasion, and metastasis, making it an ideal strategy for tumor therapy. Herein, biomimetic cancer cell membrane-coated nanodrugs (mBPP NPs) have been prepared by integrating (i) homotypic cancer cell membranes for evading immune cell phagocytosis to increase drug accumulation, (ii) protocatechuic acid for tumor vascular targeting along with chemotherapy effect, and (iii) near-infrared phototherapeutic agent diketopyrrolopyrrole derivative for photodynamic/photothermal synergetic therapy. The mBPP NPs exhibit high biocompatibility, superb phototoxicity, excellent antiangiogenic ability, and double-trigging cancer cell apoptosis in vitro. More significantly, mBPP NPs could specifically bind to tumor cells and vasculature after intravenous injection, inducing fluorescence and photothermal imaging-guided tumor ablation without recurrence and side effects in vivo. The biomimetic mBPP NPs could cause drug accumulation at the tumor site, inhibit tumor neovascularization, and improve phototherapy efficiency, providing a novel avenue for cancer treatment.
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Nanopartículas , Nanoestruturas , Neoplasias , Fotoquimioterapia , Humanos , Biomimética , Nanopartículas/uso terapêutico , Fototerapia , Neoplasias/patologia , Linhagem Celular TumoralRESUMO
[This corrects the article DOI: 10.1039/C7RA06551E.].
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The gut microbiomes of arthropods have significant impact on key physiological functions such as nutrition, reproduction, behavior, and health. Spiders are diverse and numerically dominant predators in crop fields where they are potentially important regulators of pests. Harnessing spiders to control agricultural pests is likely to be supported by an understanding of their gut microbiomes, and the environmental drivers shaping microbiome assemblages. This study aimed to deciphering the gut microbiome assembly of these invertebrate predators and elucidating potential implications of key environmental constraints in this process. Here, we used high-throughput sequencing to examine for the first time how the assemblages of bacteria in the gut of spiders are shaped by environmental variables. Local drivers of microbiome composition were globally-relevant input use system (organic production vs. conventional practice), and crop identity (Chinese cabbage vs. cauliflower). Landscape-scale factors, proportion of forest and grassland, compositional diversity, and habitat edge density, also strongly affected gut microbiota. Specific bacterial taxa were enriched in gut of spiders sampled from different settings and seasons. These findings provide a comprehensive insight into composition and plasticity of spider gut microbiota. Understanding the temporal responses of specific microbiota could lead to innovative strategies development for boosting biological control services of predators.
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Activatable prodrugs have drawn considerable attention for cancer cell ablation owing to their high specificity in drug delivery systems. However, phototheranostic prodrugs with dual organelle-targeting and synergistic effects are still rare due to low intelligence of their structures. Besides, the cell membrane, exocytosis, and diffusional hindrance by the extracellular matrix reduce drug uptake. Moreover, the up-regulation of heat shock protein and short singlet-oxygen lifetime in cancer cells hamper photo-ablation efficacy, especially in the mono-therapeutic model. To overcome those obstacles, we prepare an esterase-activated DM nano-prodrug, which is conjugated by diiodine-substituted fluorogenic malachite green derivative (MG-2I) and phototherapeutic agent DPP-OH via hydrolyzable ester linkage, having pH-responsiveness and genetically targetable activity for dual organelles-targeting to optimize photo-ablation efficacy. The DM nanoparticles (NPs) present improved pH-responsive photothermal/photodynamic property by the protonation of diethylaminophenyl units in acidic environment. More importantly, the MG-2I and DPP-OH moieties can be released from DM nano-prodrug through overexpressed esterase; then specifically target lysosomes and mitochondria in CT-26 Mito-FAP cells. Hence, near-infrared DM NPs can trigger parallel damage in dual-organelles with strong fluorescence and effective phototoxicity, thus inducing serious mitochondrial dysfunction and apoptotic death, showing excellent photo-ablation effect based on esterase-activated, pH-responsive, and genetically targetable activities.
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Nanopartículas , Neoplasias , Pró-Fármacos , Pró-Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Concentração de Íons de Hidrogênio , Linhagem Celular TumoralRESUMO
Mangrove forests inhabit tropical or subtropical intertidal zones and have remarkable abilities in coastline protection. Kandelia obovata is considered the most cold-tolerant mangrove species and has been widely transplanted to the north subtropical zone of China for ecological restoration. However, the physiological and molecular mechanisms of K. obovata under colder climate was still unclear. Here, we manipulated the typical climate of cold waves in the north subtropical zone with cycles of cold/recovery and analyzed the physiological and transcriptomic responses of seedlings. We found that both physiological traits and gene expression profiles differed between the first and later cold waves, indicating K. obovata seedlings were acclimated by the first cold experience and prepared for latter cold waves. 1,135 cold acclimation-related genes (CARGs) were revealed, related to calcium signaling, cell wall modification, and post-translational modifications of ubiquitination pathways. We identified the roles of CBFs and CBF-independent transcription factors (ZATs and CZF1s) in regulating the expression of CARGs, suggesting both CBF-dependent and CBF- independent pathways functioned in the cold acclimation of K. obovata. Finally, we proposed a molecular mechanism of K. obovata cold acclimation with several key CARGs and transcriptional factors involved. Our experiments reveal strategies of K. obovata coping with cold environments and provide prospects for mangrove rehabilitation and management.
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BACKGROUND: Understanding the networks of trophic interactions into which generalist predators are embedded is key to assessing their ecological role of in trophic networks and the biological control services they provide. The advent of affordable DNA metabarcoding approaches greatly facilitates quantitative understanding of trophic networks and their response to environmental drivers. Here, we examine how key environmental gradients interact to shape predation by Lycosidae in highly dynamic vegetable growing systems in China. RESULTS: For the sampled Lycosidae, crop identity, pesticide use and seasons shape the abundance of prey detected in spider guts. For the taxonomic richness of prey, local- and landscape-scale factors gradients were more influential. Multivariate ordinations confirm that these crop-abundant spiders dynamically adjust their diet to reflect environmental constraints and seasonal availability to prey. CONCLUSION: Plasticity in diet composition is likely to account for the persistence of spiders in relatively ephemeral brassica crops. Our findings provide further insights into the optimization of habitat management for predator-based biological control practices. © 2022 Society of Chemical Industry.
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Cadeia Alimentar , Aranhas , Animais , Estações do Ano , Código de Barras de DNA Taxonômico , Ecossistema , Comportamento Predatório/fisiologia , Aranhas/fisiologia , DNARESUMO
MAIN CONCLUSION: Whole-genome duplication, gene family and lineage-specific genes analysis based on high-quality genome reveal the adaptation mechanisms of Avicennia marina to coastal intertidal habitats. Mangrove plants grow in a complex habitat of coastal intertidal zones with high salinity, hypoxia, etc. Therefore, it is an interesting question how mangroves adapt to the unique intertidal environment. Here, we present a chromosome-level genome of the Avicennia marina, a typical true mangrove with a size of 480.43 Mb, contig N50 of 11.33 Mb and 30,956 annotated protein-coding genes. We identified 621 Avicennia-specific genes that are mainly related to flavonoid and lignin biosynthesis, auxin homeostasis and response to abiotic stimulus. We found that A. marina underwent a novel specific whole-genome duplication, which is in line with a brief era of global warming that occurred during the paleocene-eocene maximum. Comparative genomic and transcriptomic analyses outline the distinct evolution and sophisticated regulations of A. marina adaptation to the intertidal environments, including expansion of photosynthesis and oxidative phosphorylation gene families, unique genes and pathways for antibacterial, detoxifying antioxidant and reactive oxygen species scavenging. In addition, we also analyzed salt gland secretion-related genes, and those involved in the red bark-related flavonoid biosynthesis, while significant expansions of key genes such as NHX, 4CL, CHS and CHI. High-quality genomes in future investigations will facilitate the understand of evolution of mangrove and improve breeding.
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Avicennia , Adaptação Fisiológica/genética , Avicennia/genética , Ecossistema , Flavonoides/genética , Melhoramento VegetalRESUMO
Objectives: To compare patients with atrial fibrillation (AF) undergoing left atrial appendage closure (LAAC) with catheter ablation (CA) and those without CA. Background: The CA of AF may cause ridge edema, which may affect the safety of LAAC. Methods: Patients with AF (N = 98) who underwent LAAC (combined CA + LAAC procedure group; N = 51) or alone (LAAC group; N = 47) received pre-procedural, intra-procedural, and 6 week post-procedural transesophageal echocardiography (TEE). The depth and ostial diameter of LAA, device compression, residual leak, and ridge thickness were evaluated in the patients who had undergone combined and alone procedures, as well as images of LAA and primary clinical characteristics. Results: A residual leak was identified in 27 patients at 6 weeks after implantation by TEE (19 in the combined procedures group and eight in the alone group; p = 0.04). The combined procedure group had a significantly higher rate of a new residual leak than the alone group (25.5 vs. 8.5%; p = 0.03). Meanwhile, compared with at the time of implant, a smaller amount of device compression ratio was significant after 6 weeks (22.44 ± 3.90 vs. 19.59 ± 5.39; p = 0.03). There was no significant difference between both groups in all-cause mortality, cardiovascular mortality, and TIA/stroke/system embolism. Conclusion: The combined procedures of CA and LAAC for AF are feasible and safe; however, during the follow-up period, we found that the resolution of ridge edema caused by CA might cause an increased residual leak and a smaller device compression ratio.
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Constructing floating photocatalysts with highly efficient visible-light utilization is a promising approach for practical photocatalytic wastewater treatment. In this study, we anchored bismuth oxybromo-iodide (BiOBrxI1-x (0 ≤ x ≤ 1)) on flexible electrospun polyacrylonitrile (PAN) nanofiber mats to create BiOBrxI1-x@PAN nanofibers with tunable light absorption properties as floating photocatalysts at room temperature. As x increased, the photocatalytic activity of the BiOBrxI1-x@PAN nanofibers with similar loading content initially increased, and then decreased, for the degradation of bisphenol A (BPA) and methyl orange (MO) under visible-light irradiation (λ > 420 nm) conditions. The BiOBrxI1-x@PAN (0 < x < 1) nanofibers exhibited better photocatalytic performance compared to the BiOBr@PAN and BiOI@PAN nanofibers. Under visible-light irradiation, the BPA degradation rate of the BiOBr0.5I0.5@PAN nanofibers was 1.9 times higher than that of the BiOI@PAN nanofibers, while the BiOBr@PAN nanofibers had no noticeable degradation performance. The MO degradation rate of the BiOBr0.5I0.5@PAN nanofibers was 2.5 and 3.2 times higher than that of the BiOBr@PAN and BiOI@PAN nanofibers, respectively. The enhanced performance possibly originated from a balance between the light absorption and redox capabilities, along with efficient separation of electron-hole pairs in the BiOBr0.5I0.5@PAN nanofibers, as determined by ultraviolet-visible diffuse reflectance spectroscopy, X-ray photoelectron spectra analysis of the valence bands, and photocurrent response characterization. Compared to the powder structures, the BiOBrxI1-x@PAN nanofibers showed enhanced performance due to the excellent dispersion and immobilization of the BiOBrxI1-x solid solution, which provided more active sites during photocatalytic degradation. In addition, their flexible self-supporting structures allowed for floating photocatalysis near the water surface. They could be reused directly without separation and maximized the absorption of visible light during the photocatalytic reaction. Therefore, these solid-solution-based floatable nanofiber photocatalysts are good potential candidates for wastewater treatment applications.
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Strobilanthes cusia (Nees) Kuntze is an important plant used to process the traditional Chinese herbal medicines "Qingdai" and "Nanbanlangen". The key active ingredients are indole alkaloids (IAs) that exert antibacterial, antiviral, and antitumor pharmacological activities and serve as natural dyes. We assembled the S. cusia genome at the chromosome level through combined PacBio circular consensus sequencing (CCS) and Hi-C sequencing data. Hi-C data revealed a draft genome size of 913.74 Mb, with 904.18 Mb contigs anchored into 16 pseudo-chromosomes. Contig N50 and scaffold N50 were 35.59 and 68.44 Mb, respectively. Of the 32,974 predicted protein-coding genes, 96.52% were functionally annotated in public databases. We predicted 675.66 Mb repetitive sequences, 47.08% of sequences were long terminal repeat (LTR) retrotransposons. Moreover, 983 Strobilanthes-specific genes (SSGs) were identified for the first time, accounting for ~2.98% of all protein-coding genes. Further, 245 putative centromeric and 29 putative telomeric fragments were identified. The transcriptome analysis identified 2,975 differentially expressed genes (DEGs) enriched in phenylpropanoid, flavonoid, and triterpenoid biosynthesis. This systematic characterization of key enzyme-coding genes associated with the IA pathway and basic helix-loop-helix (bHLH) transcription factor family formed a network from the shikimate pathway to the indole alkaloid synthesis pathway in S. cusia. The high-quality S. cusia genome presented herein is an essential resource for the traditional Chinese medicine genomics studies and understanding the genetic underpinning of IA biosynthesis.