Smartphone-integrated ratiometric fluorescence sensing platform based on bimetallic metal-organic framework nanowires for anthrax biomarker detection.

Developing an intelligent, sensitive, and visual strategy for quickly identifying anthrax biomarkers is crucial for ensuring food safety and preventing disease outbreaks. Herein, a smartphone-integrated ratiometric fluorescent sensing platform based on bimetallic metal-organic framework (Eux/Tb1-x-MOF) nanowires was designed for specific recognition of pyridine-2,6-dicarboxylic acid (DPA, anthrax biomarker). The Eux/Tb1-x-MOF was prepared by coordinating Eu3+ and Tb3+ with BBDC ligands, which exhibited a uniform fibrous morphology and dual-emission fluorescence at 543 and 614 nm. After the introduction of DPA, the red emission at 614 nm displayed obvious fluorescence quenching, while the green emission at 543 nm was gradually enhanced. The ratiometric sensing offered a wide linear equation in the range of 0.06-15 µg/mL and a low detection limit (LOD) of 20.69 ng/mL. Furthermore, a portable smartphone installing the color recognition application can achieve sensitive, real-time, and visual detection of DPA. As a simple and effective smartphone-assisted sensing platform, this work holds admirable promise to broaden the applications in biomarker real-time determinations and other fields.

Highly sensitive fluorescent quantification of carbendazim by two-dimensional Tb-MOF nanosheets for food safety.

Carbendazim (CBZ), a well-known benzimidazole pesticide, is utilized in agriculture to prevent and cure plant diseases caused by fungi. Residual CBZ in food poses serious threat to human health. Herein, a fluorescent two-dimensional terbium-based metal-organic framework (2D Tb-MOF) nanosheet sensor was developed for the rapid and ultrasensitive detection of CBZ. The 2D Tb-MOF nanosheets, prepared with Tb3+ ions and 5-borono-1,3-benzenedicarboxylic acid (BBDC) as the precursors, exhibited excellent optical properties. Upon the addition of CBZ, the fluorescence of Tb-MOF nanosheets was quenched because of the inner filter effect (IFE) and dynamic quenching. The fluorescence sensor offered two linear ranges of 0.06-4 and 4-40 µg/mL with a low detection limit of 17.95 ng/mL. Furthermore, the proposed sensing platform was successfully applied to assay CBZ in apples and tea, and satisfactory results were obtained. This study provides an effective alternative strategy for the qualitative and quantitative determination of CBZ to ensure food safety.

An ER-Horse Detonating Stress Cascade for Hepatocellular Carcinoma Nanotherapy.

Persisting and excessive endoplasmic reticulum stress (ERS) can evoke rapid cell apoptosis. Therapeutic interference of ERS signaling holds enormous potential for cancer nanotherapy. Herein, a hepatocellular carcinoma (HCC) cell-derived ER vesicle (ERV) encapsulating siGRP94, denoted as ER-horse, has been developed for precise HCC nanotherapy. Briefly, ER-horse, like the Trojan horse, was recognized via homotypic camouflage, imitated the physiological function of ER, and exogenously opened the Ca2+ channel. Consequently, the mandatory pouring-in of extracellular Ca2+ triggered the aggravated stress cascade (ERS and oxidative stress) and apoptosis pathway with the inhibition of unfolded protein response by siGRP94. Collectively, our findings provide a paradigm for potent HCC nanotherapy via ERS signaling interference and exploring therapeutic interference of physiological signal transduction pathways for precision cancer therapy.

Loss of NSE-4 Perturbs Genome Stability and DNA Repair in Caenorhabditis elegans.

The Structural Maintenance of Chromosomes (SMC) complex plays an important role in maintaining chromosome integrity, in which the SMC5/6 complex occupies a central position by facilitating mitotic and meiotic processes as well as DNA repair. NSE-4 Kleisin is critical for both the organization and function of the SMC5/6 complex, bridging NSE1 and NSE3 (MAGE related) with the head domains of the SMC5 and SMC6 proteins. Despite the conservation in protein sequence, no functional relevance of the NSE-4 homologous protein (NSE-4) in Caenorhabditis elegans has been reported. Here, we demonstrated the essential role of C. elegans NSE-4 in genome maintenance and DNA repair. Our results showed that NSE-4 is essential for the maintenance of chromosomal structure and repair of a range of chemically induced DNA damage. Furthermore, NSE-4 is involved in inter-sister repair during meiosis. NSE-4 localizes on the chromosome and is indispensable for the localization of NSE-1. Collectively, our data from this study provide further insight into the evolutionary conservation and diversification of NSE-4 function in the SMC-5/6 complex.

Fluorescent lanthanide metal-organic framework for rapid and ultrasensitive detection of methcathinone in human urine.

Methcathinone (MC), a new and easily abused psychoactive substance, not only has a rigorous impact on public security, but also endangers people's health. Herein, novel fluorescent europium metal-organic frameworks (Eu-MOF) were synthesized through a facile one-step solvothermal strategy and utilized as an effective "signal-off" sensing platform for rapid and ultrasensitive detection of MC. The as-fabricated Eu-MOF possessed superior optical properties encompassing bright red fluorescence and good photostability. In the presence of MC, the fluorescence of Eu-MOF was significantly quenched, mainly attributing to the internal filtering effect between Eu-MOF and MC. The fluorescent signal showed high selectivity for MC over other illicit drugs, and offered two linear ranges of 1-100 ng/mL and 100-4000 ng/mL with a detection limit of 0.40 ng/mL. Strikingly, the nanoprobe could be applied for the assay of MC in human urine with satisfactory recoveries and acceptable results. This work provides a promising route for MC detection to effectively control illicit drug pandemic worldwide.

Hierarchical self-uncloaking CRISPR-Cas13a-customized RNA nanococoons for spatial-controlled genome editing and precise cancer therapy.

CRISPR-Cas13a holds enormous potential for developing precise RNA editing. However, spatial manipulation of CRISPR-Cas13a activity remains a daunting challenge for elaborately regulating localized RNase function. Here, we designed hierarchical self-uncloaking CRISPR-Cas13a-customized RNA nanococoons (RNCOs-D), featuring tumor-specific recognition and spatial-controlled activation of Cas13a, for precise cancer synergistic therapy. RNCOs-D consists of programmable RNA nanosponges (RNSs) capable of targeted delivery and caging chemotherapeutic drug, and nanocapsules (NCs) anchored on RNSs for cloaking Cas13a/crRNA ribonucleoprotein (Cas13a RNP) activity. The acidic endo/lysosomal microenvironment stimulates the outer decomposition of NCs with concomitant Cas13a RNP activity revitalization, while the inner disassembly through trans-cleavage of RNSs initiated by cis-recognition and cleavage of EGFR variant III (EGFRvIII) mRNA. RNCOs-D demonstrates the effective EGFRvIII mRNA silencing for synergistic therapy of glioblastoma cancer cells in vitro and in vivo. The engineering of RNSs, together with efficient Cas13a activity regulation, holds immense prospect for multimodal and synergistic cancer therapy.

Zippered G-quadruplex/hemin DNAzyme: exceptional catalyst for universal bioanalytical applications.

G-quadruplex (G4)/hemin DNAzyme is promising horseradish peroxidase (HRP)-mimic candidate in the biological field. However, its relatively unsatisfactory catalytic capacity limits the potential applications. Inspired by nature protease, we conducted a proximity-enhanced cofactor assembly strategy (PECA) to form an exceptional HRP mimic, namely zippered G4/hemin DNAzyme (Z-G4/H). The hybridization of short oligonucleotides induced proximity assembly of the DNA-grafted hemin (DGH) with the complementary G4 sequences (cG4s), mimicking the tight configuration of protease cofactor and apoenzyme. The detailed investigations of catalytic efficiency and mechanism verified the higher activity, more rapid catalytic rate and high environmental tolerance of the Z-G4/H than the classical G4/hemin DNAzymes (C-G4/H). Furthermore, a proximity recognition transducer has been developed based on the PECA for sensitive detection of gene rearrangement and imaging human epidermal growth factor receptor 2 protein (HER2) dimerization on cell surfaces. Our studies demonstrate the high efficiency of Z-G4/H and its universal application potential in clinical diagnostics and biomolecule interaction research. It also may offer significant opportunities and inspiration for the engineering of the protease-free mimic enzyme.

Eco-Friendly Preparation of Epoxy-Rich Graphene Oxide for Wound Healing.

Despite the ever-growing endangerment caused by the multidrug resistance (MDR) of bacteria, the development of effective antibacterial materials still remains a global challenge. Current antibiotic therapies cannot simultaneously inactivate bacteria and accelerate wound healing. This study aimed to originally separate the intercalation of MnO3+ and the oxidation processes to synthesize epoxy-rich graphene oxide (erGO) nanofilms via an eco-friendly synthetic route, which possessed low density and large lamellar distribution and was rich in epoxide. Importantly, the MnO3+ could be separated from the product and recycled for preparing the next generation of erGO nanofilms, which was quite economical and eco-friendly. The erGO nanofilm was capable of successfully inhibiting Gram-negative bacteria and even had excellent growth-inhibitory effects on Gram-positive bacteria including multidrug resistance (MDR) bacteria, as evidenced by antibacterial phenomena. Additionally, the erGO nanofilm with high •C density formed from epoxide exerted excellent antibacterial effects through tight membrane wrapping and induction of lipid peroxidation. The wound-healing property of the erGO nanofilm was evaluated via treatments of wounds infected by Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), which not only killed bacteria but also accelerated wound healing in mice with a skin infection. The novel erGO nanofilm with dual antimicrobial mechanisms might serve as a promising multifunctional antimicrobial agent for medical wound dressing with high biocompatibility.

Recent advances in the construction and analytical applications of carbon dots-based optical nanoassembly.

Recently, more and more attention has been focused on the construction and analytical applications of optical nanoassembly through combining carbon dots (CDs) with various other functional nanomaterials. The rational design and manufacture of CDs-based optical nanoassembly will be critical to meeting the needs of analytical science. The last decade has witnessed the immense potential of CDs-based optical nanoassembly in multiple sensing applications owing to their controlled optical properties, adjustable surface chemistry and microscopic morphology. This feature article collects the recent advances in the research and development of CDs-based optical nanoassembly and their applications in analytical sensors, aiming to provide vital insights and suggestions to inspire their broad sensing applications.

Surface plasmon resonance biosensor using hydrogel-AuNP supramolecular spheres for determination of prostate cancer-derived exosomes.

Based on the hydrogel-AuNP supramolecular sphere (H-Au), a label-free and real-time surface plasmon resonance imaging biosensor has been developed for highly sensitive and specific determination of prostate cancer cell-derived exosomes. After integrating the signal amplification effect of the mass cumulative hydrogel and the LSPR effect of AuNPs with high specific aptamer, the SPRi biosensor for exosome detection exhibited a wide linear range from 1.00 × 105 to 1.00 × 107 particles/mL with a limit of detection of 1.00 × 105 particles/mL. Most importantly, with a strong correlation between the SPRi signal and the t-PSA value measured by the clinical chemiluminescence immunoassay, this biosensor displayed excellent practicability for human serum analysis, which exhibits great potential applications in disease diagnosis and bioanalysis. Prostate cancer has been one of the most threatening diseases in human life and health nowadays. In particular, as cancer metastasizes, it is more likely to cause fracture, paraplegia, and even fatal consequences. However, the predominant t-PSA test needs further improvement for the deficiencies of limited specificity and sensitivity, which is prone to false positive. As one of the noninvasive markers of liquid biopsies, exosome has the potential to be a substitute for t-PSA, which can provide specific and predictive information in disease diagnosis and prognosis. Herein, based on the hydrogel-AuNP supramolecular sphere (H-Au), a label-free and real-time surface plasmon resonance biosensor has been developed for highly sensitive and specific detection of prostate cancer cell-derived exosomes. After integrating the signal amplification effect of mass cumulative hydrogel and LSPR effect of AuNPs with high specific aptamer, this developed SPRi biosensor for exosome detection exhibited a wide linear range from 1.00 × 105 to 1.00 × 107 particles/mL with a limit of detection down to 1.00 × 105 particles/mL. Most importantly, with a strong correlation between the SPRi signal and the t-PSA value measured by the clinical chemiluminescence immunoassay, this biosensor displayed excellent practicability in human serum, which exhibited great potential applications in disease diagnosis and bioanalysis.

Caenorhabditis elegans-Based Aspergillus fumigatus Infection Model for Evaluating Pathogenicity and Drug Efficacy.

Aspergillus fumigatus is the most reported causative pathogen associated with the increasing global incidences of aspergilloses, with the health of immunocompromised individuals mostly at risk. Monitoring the pathogenicity of A. fumigatus strains to identify virulence factors and evaluating the efficacy of potent active agents against this fungus in animal models are indispensable in current research effort. Caenorhabditis elegans has been successfully utilized as an infection model for bacterial and dimorphic fungal pathogens because of the advantages of being time-efficient, and less costly. However, application of this model to the filamentous fungus A. fumigatus is less investigated. In this study, we developed and optimized a stable and reliable C. elegans model for A. fumigatus infection, and demonstrated the infection process with a fluorescent strain. Virulence results of several mutant strains in our nematode model demonstrated high consistency with the already reported pathogenicity pattern in other models. Furthermore, this C. elegans-A. fumigatus infection model was optimized for evaluating the efficacy of current antifungal drugs. Interestingly, the azole drugs in nematode model prevented conidial germination to a higher extent than amphotericin B. Overall, our established C. elegans infection model for A. fumigatus has potential applications in pathogenicity evaluation, antifungal agents screening, drug efficacy evaluation as well as host-pathogen interaction studies.

Genome survey of Zanthoxylum bungeanum and development of genomic-SSR markers in congeneric species.

Zanthoxylum bungeanum, a spice and medicinal plant, is cultivated in many parts of China and some countries in Southeast Asia; however, data on its genome are lacking. In the present study, we performed a whole-genome survey and developed novel genomic-SSR markers of Z. bungeanum. Clean data (∼197.16 Gb) were obtained and assembled into 11185221 scaffolds with an N50 of 183 bp. K-mer analysis revealed that Z. bungeanum has an estimated genome size of 3971.92 Mb, and the GC content, heterozygous rate, and repeat sequence rate are 37.21%, 1.73%, and 86.04%, respectively. These results indicate that the genome of Z. bungeanum is complex. Furthermore, 27153 simple sequence repeat (SSR) loci were identified from 57288 scaffolds with a minimum length > 1 kb. Mononucleotide repeats (19706) were the most abundant type, followed by dinucleotide repeats (5154). The most common motifs were A/T, followed by AT/AT; these SSRs accounted for 71.42% and 11.84% of all repeats, respectively. A total of 21243 non-repeating primer pairs were designed, and 100 were randomly selected and validated by PCR analysis using DNA from 10 Z. bungeanum individuals and 5 Zanthoxylum armatum individuals. Finally, 36 polymorphic SSR markers were developed with polymorphism information content (PIC) values ranging from 0.16 to 0.75. Cluster analysis revealed that Z. bungeanum and Z. armatum could be divided into two major clusters, suggesting that these newly developed SSR markers are useful for genetic diversity and germplasm resource identification in Z. bungeanum and Z. armatum.

DNAH17-AS1 promotes pancreatic carcinoma by increasing PPME1 expression via inhibition of miR-432-5p.

BACKGROUND: The incidence and mortality rates of pancreatic carcinoma (PC) are rapidly increasing worldwide. Long noncoding RNAs (lncRNAs) play critical roles during PC initiation and progression. Since the lncRNA DNAH17-AS1 is highly expressed in PC, the regulation of DNAH17-AS1 in PC was investigated in this study. AIM: To investigate the expression and molecular action of lncRNA DNAH17-AS1 in PC cells. METHODS: The PC expression data for the lncRNA DNAH17-AS1 was downloaded from The Cancer Genome Atlas database and used to examine its profile. Western blot and reverse transcription-quantitative PCR were employed to assess protein and mRNA expression. A subcellular fractionation assay was used to determine the location of DNAH17-AS1 in cells. In addition, the regulatory effects of DNAH17-AS1 on miR-432-5p, PPME1, and tumor activity were investigated using luciferase reporter assay, MTT viability analysis, flow cytometry, and transwell migration analysis. RESULTS: DNAH17-AS1 was upregulated in PC cells and was associated with aggressive tumor behavior and poor prognosis for patients. Silencing DNAH17-AS1 promoted the apoptosis and reduced the viability, invasion, and migration of PC cells. In addition, DNAH17-AS1 served as a PC oncogene by downregulating miR-432-5p which normally directly targeted PPME1 to downregulate its expression. CONLUSION: DNAH17-AS1 functions in PC as a tumor promoter by regulating the miR-432-5p/PPME1 axis. This finding may provide new insights for PC prognosis and therapy.

A localized molecular automaton for in situ visualization of proteins with specific chemical modifications.

Given the powerful regulation roles of chemical modification networks in protein structures and functions, it is of vital importance to acquire the spatiotemporal chemical modification pattern information in a protein-specific fashion, which is by far a highly challenging task. Herein, we design a localized DNA automaton, equipped with an anticoding-coding sequential propagation algorithm, for in situ visualization of a given protein subtype with two chemical modifications of interest on the cell surface. The automaton is composed of three probes respectively for the protein and two types of modifications. Once anchored on the cell surface and triggered, the automaton performs sequential protein-localized, DNA hybridization-based computations on the proximity status of each modification type with the protein and contracts the set of close proximity information into a single fluorescence signal turn-on using the designed algorithm. The modular and scalable features of the automaton enable its operation in scaled-down versions for protein-specific identification of one given modification. Thus, this work opens up the possibility of using automata for revealing complex regulation mechanisms of protein posttranslational modifications.

Linc00511 Indicates A Poor Prognosis Of Liver Hepatocellular Carcinoma.

OBJECTIVE: To uncover the specific function of linc00511 in the progression of liver hepatocellular carcinoma (LIHC) and the underlying mechanism. PATIENTS AND METHODS: GEPIA dataset containing 9736 LIHC samples and 857 normal samples were downloaded from TCGA. Expression pattern and prognostic potential of linc00511 in LIHC were analyzed. Subsequently, expression level of linc00511 in LIHC tissues collected in our hospital and cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Differential expressions of linc00511 in LIHC with different tumor grades and metastatic status were compared. After transfection of si-linc00511, proliferative and migratory changes in Huh7 and Hep3B cells were assessed by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) and Transwell assay. Lastly, Pearson correlation analysis and qRT-PCR were conducted to investigate the interaction between linc00511 and miR-29c. RESULTS: Linc00511 was upregulated in LIHC tissues and cell lines. Its level was positively correlated to TNM staging, lymphatic metastasis and poor prognosis in LIHC patients. Knockdown of linc00511 attenuated proliferative and migratory abilities in Huh7 and Hep3B cells. In addition, miR-29c was downregulated in LIHC and negatively linked to linc00511 level. A negative interaction between linc00511 and miR-29c could be a regulatory feedback influencing the progression of LIHC. CONCLUSION: Linc00511 accelerates the proliferation and migration in LIHC, thus aggravating tumor progression. Meanwhile, linc00511 could be utilized as a hallmark predicting poor prognosis in LIHC patients.

Isolation and Characterization of a Ranavirus Associated with Disease Outbreaks in Cultured Hybrid Grouper (♀ Tiger Grouper Epinephelus fuscoguttatus × â™‚ Giant Grouper E. lanceolatus) in Guangxi, China.

An outbreak of suspected iridovirus disease in cultured hybrid grouper (♀Tiger Grouper Epinephelus fuscoguttatus × â™‚ Giant Grouper Epinephelus lanceolatus) occurred in the Guangxi Province in July, 2018. In this study, grouper iridovirus Guangxi (SGIV-Gx) was isolated from diseased hybrid grouper that were collected from Guangxi. Cytopathic effects were observed and identified in grouper spleen cells that were incubated with diseased tissue homogenates after 24 h, and the effects increased at 48 h postinfection. The transmission electron microscopy results showed that viral particles that were about 200 nm in diameter with hexagonal profiles were present in the cell cytoplasm of suspected virus-infected cells. The presence of SGIV-Gx (accession number: MK107821) was identified by polymerase chain reaction (PCR) and amplicon sequencing, which showed that this strain was most closely related to Singapore grouper iridovirus (AY521625.1). The detection of SGIV-Gx infection was further supported by novel aptamer (Q2c)-based detection technology. The effects of temperature and pH on viral infectivity were analyzed by using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and cell culture. The results indicated that SGIV-Gx was resistant to exposure to pH levels 5, 7, and 7.5 for 1 h, but its infectivity was remarkably lower at pH levels 3 and 10 after 1 h. The analyses showed that SGIV-Gx was stable for 1 h at 4°C and 25°C but was inactivated after 1 h at 40, 50, and 60°C.

Development of novel aptamer-based enzyme-linked apta-sorbent assay (ELASA) for rapid detection of mariculture pathogen Vibrio alginolyticus.

As the major opportunistic pathogen to both marine animals and humans, Vibrio alginolyticus (V. alginolyticus) has caused heavy economic losses to mariculture. ssDNA aptamer VA2 targeting live V. alginolyticus was generated by systematic evolution of ligands by exponential enrichment (SELEX) technology in our previous study. In this study, we first developed aptamer (VA2)-based enzyme-linked apta-sorbent assay (VA2-ELASA) for rapid detection of mariculture pathogen V. alginolyticus. The VA2-ELASA could achieve the rapid detection for V. alginolyticus infection with high specificity and sensitivity. The VA2-ELASA could specifically identify V. alginolyticus, but not other non-target bacterial strains. VA2-ELASA could detect V. alginolyticus at the concentration of 5 × 104 /ml, the incubation time short to 1 min and the incubation temperature as high as 45°C, which proved sensitivity and stability of the novel VA2-ELASA in this study. It took less than one hour to accomplish the detection process by VA2-ELASA. The characteristics of specificity, sensitivity and easy operation make VA2-ELASA a novel useful technology for the rapid diagnosis of pathogen V. alginolyticus in mariculture.

Filter Beacon: A Gating-Free Architecture for Protein-Specific Glycoform Imaging on Cell Surface.

The imaging characterization of spatial proximity of covalently linked structural motifs (e.g., protein-specific glycoform) is essential for thorough understanding of cellular chemistry and biology. The current imaging formats rely on gating-based mechanisms for generating correct closed-loop signaling topology, and they can suffer from low signal intensity, restricted applicability, and complicated design. We report herein the development of a mechanistically distinct filter beacon architecture for protein-specific glycoform imaging on the cell surface. The elaborate structuring of molecular beacon segment, nicking restriction site, and docking moiety lays out a general nongated design principle for passing through intended closed-loop signaling topology and sifting out false-positive open-loop leakage topology, furnishing a straightforward imaging format with high signal intensity and broad applicability. Proof-of-concept protocols have been developed for the imaging of MUC1-bound terminal sialic acid and fucose. The versatile adaptability of the protocols also enables dynamic monitoring of protein-specific glycosylation pattern changes in response to the alteration of cellular physiological states. Given the convenience for achieving multiplexed encoding and decoding, through fluorescence signals alone or together with filter beacon sequences, the filter beacon architecture should permit comprehensive imaging of diverse-structured carbohydrates on a given glycoprotein.

EGR1-induced upregulation of lncRNA FOXD2-AS1 promotes the progression of hepatocellular carcinoma via epigenetically silencing DKK1 and activating Wnt/ß-catenin signaling pathway.

Long non-coding RNAs (lncRNAs) are regarded as a group of biomarkers in the initiation and development of various cancers, including hepatocellular carcinoma (HCC). LncRNA FOXD2-AS1 has been studied in human colorectal cancer and glioma as an oncogene. However, the function and mechanism of lncRNA FOXD2-AS1 in hepatocellular carcinoma are marked. In this study, we found that high expression of FOXD2-AS1 predicted poor prognosis of HCC patients in the TCGA database. The dysregulation of FOXD2-AS1 was determined in HCC tissues and cell lines by qRT-PCR. Functionally, silenced FOXD2-AS1 efficiently suppressed HCC progression by regulating cell proliferation, apoptosis, migration and epithelial-mesenchymal transition (EMT). Mechanistically, FOXD2-AS1 was found to be activated by the transcription factor EGR1. Furthermore, FOXD2-AS1 could activate the Wnt/ß-catenin signaling pathway. The mechanism contributed to the interaction between FOXD2-AS1 and Wnt/ß-catenin signaling pathway was analyzed. It was uncovered that FOXD2-AS1 enhanced the activity of Wnt/ß-catenin signaling pathway by epigenetically silencing the inhibitor of Wnt/ß-catenin signaling pathway (DKK1). Rescue assays demonstrated that DKK1 and Wnt/ß-catenin signaling pathway involved in FOXD2-AS1-mediated HCC progression. In conclusion, our study demonstrated that EGR1-induced upregulation of lncRNA FOXD2-AS1 promotes the progression of hepatocellular carcinoma via epigenetically silencing DKK1 and activating Wnt/ß-catenin signaling pathway.

The inhibitory activities and antiviral mechanism of Viola philippica aqueous extracts against grouper iridovirus infection in vitro and in vivo.

Grouper iridovirus (GIV) is one of the most serious pathogens in mariculture and causes high mortality rates in cultured groupers; then, effective medicines for controlling GIV infections are urgently needed. Viola philippica is a well-known medicinal plant, and the application of V. philippica aqueous extracts against GIV infection was assessed by different methods in this study. The results showed that the working concentration of V. philippica aqueous extracts was 10 mg/ml. V. philippica aqueous extracts below 10 mg/ml have no significant cytotoxic effects on cell viability, while extracts over 15 mg/ml decreased cell viability and showed cytotoxic activity. V. philippica aqueous extracts had excellent inhibitory effects against GIV infection in vitro and in vivo. The possible antiviral mechanism of V. philippica was further analysed, which indicated that V. philippica did no damages to GIV particles, but it could disturb GIV binding, entry and replication in host cells. V. philippica had the best inhibitory effects against GIV during viral infection stage of binding and replication in host cells. Overall, the results suggest that appropriate concentration of V. philippica aqueous extracts has great antiviral effects, making it an interesting candidate for developing effective medicines for preventing and controlling GIV infection in farmed groupers.