Physiological and biochemical characteristics of the carbon ion beam irradiation-generated mutant strain Clostridium butyricum FZM 240 in vitro and in vivo.

Clostridium butyricum (C. butyricum) represents a new generation of probiotics, which is beneficial because of its good tolerance and ability to produce beneficial metabolites, such as short-chain fatty acids and enzymes; however, its low enzyme activity limits its probiotic efficacy. In this study, a mutant strain, C. butyricum FZM 240 was obtained using carbon ion beam irradiation, which exhibited greatly improved enzyme production and tolerance. The highest filter paper, endoglucanase, and amylase activities produced by C. butyricum FZM 240 were 125.69 U/mL, 225.82 U/ mL, and 252.28 U/mL, which were 2.58, 1.95, and 2.21-fold higher, respectively, than those of the original strain. The survival rate of the strain increased by 11.40 % and 5.60 % after incubation at 90 °C for 5 min and with simulated gastric fluid at pH 2.5 for 2 h, respectively, compared with that of the original strain. Whole-genome resequencing and quantitative real-time PCR(qRT-PCR) analysis showed that the expression of genes related to enzyme synthesis (GE000348, GE001963 and GE003123) and tolerance (GE001114) was significantly up-regulated, while that of genes related to acid metabolism (GE003450) was significantly down-regulated. On this basis, homology modeling and functional prediction of the proteins encoded by the mutated genes were performed. According to the results, the properties related to the efficacy of C. butyricum as a probiotic were significantly enhanced by carbon ion beam irradiation, which is a novel strategy for the application of Clostridium spp. as feed additives.

vB_EcoM-P896 coliphage isolated from duck sewage can lyse both intestinal pathogenic Escherichia coli and extraintestinal pathogenic E. coli.

Pathogenic Escherichia coli strains cause diseases in both humans and animals. The limiting factors to prevent as well as control infections from pathogenic E. coli strains are their pathotypes, serotypes, and drug resistance. Herein, a bacteriophage (vB_EcoM-P896) has been isolated from duck sewage. Furthermore, aside from targeting intestinal pathogenic E. coli strains like enteropathogenic E. coli, Shiga toxin-producing E. coli, entero-invasive E. coli, and enteroaggregative E. coli, vB_EcoM-P896 can cause lysis in extraintestinal pathogenic E. coli strains such as avian pathogenic E. coli. Stability analysis revealed that vB_EcoM-P896 was stable under the following conditions: temperature, 4℃-50℃; pH, 3-11. The sequencing of the vB_EcoM-P896 genome was conducted utilizing an HiSeq system (Illumina, San Diego, CA) and subjected to de novo assembling with the aid of Spades 3.11.1. The characteristics of the DNA genome were as follows: size, 170,656 bp; GC content, 40.4%; the number of putative coding regions, 294. Transmission electron microscopy analysis of morphology and genome analysis revealed that the phage vB_EcoM-P896 belonged to the order Caudovirales and the family Myoviridae. The pan-genome analysis of vB_EcoM-P896 was divided into two levels. The first level involved the analysis of 91 strains of muscle tail phages, which were mainly divided into 5 groups. The second level involved the analysis of 24 strains of myophage with high homology. Of the 1480 gene clusters, 23 were shared core genes. Neighbor-joining phylogenetic trees were constructed using the Poisson model with MEGA6.0 based on the conserved sequences of phage proteins, the amino acid sequence of the terminase large subunit, and tail fibrin. Further analysis revealed that vB_EcoM-P896 was a typical T4-like potent phage with potential clinical applications.

Exploring TRF2-Dependent DNA Distortion Through Single-DNA Manipulation Studies.

TRF2 is a component of shelterin, a telomere-specific protein complex that protects the ends of mammalian chromosomes from DNA damage signaling and improper repair. TRF2 functions as a homodimer and its interaction with telomeric DNA has been studied, but its full-length DNA-binding properties are unknown. This study examines TRF2's interaction with single-DNA strands and focuses on the conformation of the TRF2-DNA complex and TRF2's preference for DNA chirality. The results show that TRF2-DNA can switch between extended and compact conformations, indicating multiple DNA-binding modes, and TRF2's binding does not have a strong preference for DNA supercoiling chirality when DNA is under low tension. Instead, TRF2 induces DNA bending under tension. Furthermore, both the N-terminal domain of TRF2 and the Myb domain enhance its affinity for the telomere sequence, highlighting the crucial role of multivalent DNA binding in enhancing its affinity and specificity for telomere sequence. These discoveries offer unique insights into TRF2's interaction with telomeric DNA.

Interrogation and validation of the interactome of neuronal Munc18-interacting Mint proteins with AlphaFold2.

Munc18-interacting proteins (Mints) are multidomain adaptors that regulate neuronal membrane trafficking, signaling, and neurotransmission. Mint1 and Mint2 are highly expressed in the brain with overlapping roles in the regulation of synaptic vesicle fusion required for neurotransmitter release by interacting with the essential synaptic protein Munc18-1. Here, we have used AlphaFold2 to identify and then validate the mechanisms that underpin both the specific interactions of neuronal Mint proteins with Munc18-1 as well as their wider interactome. We found that a short acidic α-helical motif within Mint1 and Mint2 is necessary and sufficient for specific binding to Munc18-1 and binds a conserved surface on Munc18-1 domain3b. In Munc18-1/2 double knockout neurosecretory cells, mutation of the Mint-binding site reduces the ability of Munc18-1 to rescue exocytosis, and although Munc18-1 can interact with Mint and Sx1a (Syntaxin1a) proteins simultaneously in vitro, we find that they have mutually reduced affinities, suggesting an allosteric coupling between the proteins. Using AlphaFold2 to then examine the entire cellular network of putative Mint interactors provides a structural model for their assembly with a variety of known and novel regulatory and cargo proteins including ADP-ribosylation factor (ARF3/ARF4) small GTPases and the AP3 clathrin adaptor complex. Validation of Mint1 interaction with a new predicted binder TJAP1 (tight junction-associated protein 1) provides experimental support that AlphaFold2 can correctly predict interactions across such large-scale datasets. Overall, our data provide insights into the diversity of interactions mediated by the Mint family and show that Mints may help facilitate a key trigger point in SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) complex assembly and vesicle fusion.

Screening of the Active Substances for the Assessment of Walnut Kernel in the Treatment of Scopolamine-Induced AD Animals.

SCOPE: Alzheimer's disease (AD) has been a challenge and hotspot in the field of neuroscience research due to the high morbidity. As we all know, walnut kernel (WK) ingestion has been linked to benefits to brain health and has the function of improving memory. This study follows the AD model induced by scopolamine to reveal the active fractions and substances of walnut in the treatment of AD. METHODS AND RESULTS: The histopathological analysis and brain tissue biochemistry assay are revealed the active fractions of WK, and this result determines that walnut kernel organic acids have significant therapeutic effect on AD. The strategy of studying ingredients pointed at lesions is integrated to ascertain the selected brain-targeted effective substances of WK for blood-brain barrier by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry, and a total of eight organic acids are figured out definite absorptivity in rat brains. Finally, the binding interaction between the effective substances and target proteins is analyzed by molecular docking, and the main function related active markers are ascertained as glansreginin A, glansreginic acid, ellagic acid, and ellagic acid 4-O-xyloside. CONCLUSIONS: The comprehensive process is helpful to the clinical application of WK as a promising cholinesterase inhibitors for nutritional intervention.

Engineering Platelet Membrane-Coated Bimetallic MOFs as Biodegradable Nanozymes for Efficient Antibacterial Therapy.

Nanocatalytic-based wound therapeutics present a promising strategy for generating reactive oxygen species (ROS) to antipathogen to promote wound healing. However, the full clinical potential of these nanocatalysts is limited by their low reactivity, limited targeting ability, and poor biodegradability in the wound microenvironment. Herein, a bio-organic nanozyme is developed by encapsulating a FeZn-based bimetallic organic framework (MOF) (MIL-88B-Fe/Zn) in platelet membranes (PM@MIL-88B-Fe/Zn) for antimicrobial activity during wound healing. The introduction of Zn in MIL-88B-Fe/Zn modulates the electronic structure of Fe thus accelerating the catalytic kinetics of its peroxidase-like activity to catalytically generate powerful ROS. The platelet membrane coating of MOF innovatively enhanced the interaction between nanoparticles and the biological environment, further developing bacterial-targeted therapy with excellent antibacterial activity against both gram-positive and gram-negative bacteria. Furthermore, this nanozyme markedly suppressed the levels of inflammatory cytokines and promoted angiogenesis in vivo to effectively treat skin surface wounds and accelerate wound healing. PM@MIL-88B-Fe/Zn exhibited superior biodegradability, favourable metabolism and non-toxic accumulation, eliminating concerns regarding side effects from long-term exposure. The high catalytic reactivity, excellent targeting features, and biodegradability of these nanoenzymes developed in this study provide useful insights into the design and synthesis of nanocatalysts/nanozymes for practical biomedical applications.

Nanoreactor based on Cu nanoparticles confined in B, N co-doped porous carbon nanotubes for glutathione biosensing.

A cost-effective approach has been developed to synthesize Cu nanoparticles encapsulated into B and N double-doped carbon nanotubes (Cu@BCNNTs) by one-step pyrolysis. According to the specific binding of Cu-Cl and Cu-glutathione (GSH), we employed Cu@BCNNTs to build an electrochemical sensing platform to detect GSH. The unique space-confined structure can prevent Cu nanoparticles from agglomeration. In addition, B and N co-doped porous hollow tubes can improve the electrochemical conductivity, expand the number of active sites, enhance surface adsorption, and shorten the transport path. These favorable characteristics of Cu@BCNNTs make them have excellent electrocatalytic properties. These results display that the prepared sensor can detect GSH from 0.5 to 120 µM with a detection limit of 0.024 µM. The obtained sensors can be successfully applied in the human serum with recovery of GSH ranging from 100.2 to 103.9%. This work provides a new vision to synthesize nanoparticles confined in a hollow tube for the applications in biosensing and medical diagnostics.

The attenuation effect of licorice on the hepatotoxicity of Euodiae Fructus by inhibiting the formation of protein conjugates and GSH depletion.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine and food, Euodiae Fructus (EF) is widely used in clinics to relieve pain and prevent vomiting and for making tea for more than a thousand years. In recent years, hepatotoxic reactions to EF have been reported. The intermediates produced by evodiamine and rutaecarpine metabolism in vitro were captured by glutathione (GSH), suggesting that the toxicity of EF may be related to metabolic activation. Whether licorice can inhibit the metabolic activation of EF has not been reported, which needed an effective strategy to clarify the correlation between protein conjugates and hepatotoxicity and the attenuation mechanism of licorice processing. AIM OF THE STUDY: This study aimed to explore the toxic components and mechanisms of EF based on metabolic activation and the detoxification of licorice. MATERIALS AND METHODS: The content and toxicity index of protein conjugates in the liver were determined by orally administering mice and rats with EF. The attenuation mechanism of licorice was examined in cell and enzymology experiments. RESULTS: The change in evodiamine-cysteinylglycine (EVO-Cys-Gly) and evodiamine-cysteine (EVO-Cys) levels was consistent with the change in hepatotoxicity. Licorice inhibited the formation of the protein conjugates of EF and increased the content of GSH in L02 cells. CONCLUSION: EF mediated by P450 enzymes produced toxic intermediates, which combined with cysteine residues in animal liver and inactivate them, leading to hepatotoxicity. Interestingly, licorice can alleviate the GSH depletion caused by EF and inhibit the production of protein conjugates by inhibiting P450 enzymes.

Construction of Clostridium tyrobutyricum strain and ionic membrane technology combination pattern for refinery final molasses recovery and butyric acid production.

Introduction: Clostridium tyrobutyricum has considerable prospect in the production of organic acids. Globally, refinery final molasses is rich in sugar and reported to have high levels of accumulation and high emission costs, recognized as an excellent substrate for C. tyrobutyricum fermentation, but there is no suitable method available at present. Methods: In this study, an acid-base treatment combined with a new green membrane treatment technology - a dynamic ion-exchange membrane -was used to pretreat refinery final molasses, so that it could be used for C. tyrobutyricum to produce butyric acid. A high-performance liquid chromatography method was established to determine the conversion of a large amount of sucrose into fermentable sugars (71.88 g/L glucose and 38.06 g/L fructose) in the treated refinery final molasses. The process of sequential filtration with 3, 1, and 0.45 µm-pore diameter dynamic ion-exchange membranes could remove impurities, pigments, and harmful substances from the refinery final molasses, and retain the fermentable sugar. Results and discussion: This means that refinery final molasses from the sugar industry could be utilized as a high-value by-product and used for the growth of C. tyrobutyricum, with industrial feasibility and economic competitiveness. Using the treated refinery final molasses as a carbon source, C. tyrobutyricum was screened by the method of adaptive evolution. The strain with butyric acid yielded 52.54 g/L, and the yield of the six carbon sugar was increased from 0.240 to 0.478 g/g. The results showed that combination of C. tyrobutyricum and ionic membrane technology broke through the bottleneck of its utilization of refinery final molasses. This study provided an innovative idea for the C. tyrobutyricum fermentation to produce butyric acid.

Identification of Subunits for Novel Universal Vaccines against Three Predominant Serogroups and the Emerging O145 among Avian Pathogenic Escherichia coli by Pan-RV Pipeline.

Avian pathogenic Escherichia coli, a causative agent of avian colibacillosis, has been causing serious economic losses in the poultry industry. The increase in multidrug-resistant isolates and the complexity of the serotypes of this pathogen, especially the recently reported emergence of a newly predominant serogroup of O145, make the control of this disease difficult. To address this challenge, a high-throughput screening approach, called Pan-RV (Reverse vaccinology based on pangenome analysis), is proposed to search for universal protective antigens against the three traditional serogroups and the newly emerged O145. Using this approach, a total of 61 proteins regarded as probable antigens against the four important serogroups were screened from the core genome of 127 Avian pathogenic Escherichia coli (APEC) genomes, and six were verified by Western blots using antisera. Overall, our research will provide a foundation for the development of an APEC subunit vaccine against avian colibacillosis. Given the exponential growth of whole-genome sequencing (WGS) data, our Pan-RV pipeline will make screening of bacterial vaccine candidates inexpensive, rapid, and efficient. IMPORTANCE With the emergence of drug resistance and the newly predominant serogroup O145, the control of Avian pathogenic Escherichia coli is facing a serious challenge; an efficient immunological method is urgently needed. Here, for the first time, we propose a high-throughput screening approach to search for universal protective antigens against the three traditional serogroups and the newly emerged O145. Importantly, using this approach, a total of 61 proteins regarded as probable antigens against the four important serogroups were screened, and three were shown to be immunoreactive with all antisera (covering the four serogroups), thereby providing a foundation for the development of APEC subunit vaccines against avian colibacillosis. Further, our Pan-RV pipeline will provide immunological control strategies for pathogens with complex and variable genetic backgrounds such as Escherichia coli and will make screening of bacterial vaccine candidates more inexpensive, rapid, and efficient.

Accuracy of contrast-enhanced ultrasound in diagnosing extracranial carotid occlusion: A meta-analysis.

AIM: This study aimed to assess the accuracy of contrast-enhanced ultrasound (CEUS) in detecting extracranial carotid artery occlusion. MATERIALS AND METHODS: A systematic literature search was conducted in the Cochrane, PubMed, and EMBASE databases. Prospective or retrospective studies that reported sensitivity and specificity of CEUS for the diagnosis of carotid artery occlusion were selected. Eight studies (354 arteries) were included in the meta-analysis. A bivariate random-effect model was used to estimate overall sensitivity and specificity. The results were also summarized by developing a summary receiver operating characteristic (SROC) curve. RESULTS: The overall sensitivity, specificity, positive, and negative likelihood ratios were 0.99 (95% CI: 0.83-1.00), 0.97 (95% CI: 0.90-0.99), 30.0 (95% CI: 9.8-91.4), and 0.01 (95% CI: 0.00-0.21), respectively; the odds ratio for diagnosis was 4,796 (95% CI: 119-192,584). CONCLUSION: The diagnostic test accuracy suggests that CEUS is a reliable tool for diagnosis of extracranial carotid artery occlusion.

Large-scale microbiome analysis reveals bacterial community characteristics in typical Chinese herbal slices.

Chinese herbal slices (CHSs) are closely associated to microorganisms, whether they are endophytic or epiphytic in plants, or introduced during processing. In this study, the structures and predicted functions of microbial communities in 150 batches of samples from five types of CHSs were investigated by combining pure culture and 16 S rDNA amplicon sequencing. Bile-salt-tolerant gram-negative bacteria were detected in 56.0% of samples, and Salmonella was detected in two batches of Glycyrrhiza slices and in one batch of Rheum slices. The main genera from the Enterobacteriaceae, Bacillaceae, Fibrobacteraceae, and Pseudomonadaceae families were assessed in typical colonies. Amplicon sequencing identified 1200 bacterial genera, including some pharmacopeial-controlled bacteria and many beneficial endophytes of medicinal plants. Around 65% of the genera co-occurred in all five CHSs. In clustering based on different algorithms, the samples from each CHS type were relatively clustered, with some overlap. Ranked from highest to lowest diversity, the CHSs were Rheum, Angelica, Astragalus, Codonopsis, and Glycyrrhiza. Each CHS had its indicator species. Functional annotations suggest that potential microbial transformation uses CHSs as substrates and microbial communities as transformants. Overall, it was demonstrated that, based on their complementary advantages, high-throughput sequencing technology and traditional pure-culture technology together can fully assess the microbial load of CHSs and reduce the misdetection rate. We observed large microbial communities in typical CHSs, demonstrating differences and similarities among different CHS types. These results provide a reference for establishing new microbial limit criteria for CHSs and highlight the importance of further correlating CHS microbial community structure and function. Supplementary Information: The online version contains supplementary material available at 10.1007/s11756-022-01199-0.

Evaluating the utility of an immune checkpoint-related lncRNA signature for identifying the prognosis and immunotherapy response of lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most frequent subtype of lung cancer globally. However, the survival rate of lung adenocarcinoma patients remains low. Immune checkpoints and long noncoding RNAs are emerging as vital tools for predicting the immunotherapeutic response and outcomes of patients with lung adenocarcinoma. It is critical to identify lncRNAs associated with immune checkpoints in lung adenocarcinoma patients. In this study, immune checkpoint-related lncRNAs (IClncRNAs) were analysed and identified by coexpression. Based on the immune checkpoint-related lncRNAs, we divided patients with lung adenocarcinoma into two clusters and constructed a risk model. Kaplan-Meier analysis, Gene Set Enrichment Analysis, and nomogram analysis of the 2 clusters and the risk model were performed. Finally, the potential immunotherapeutic prediction value of this model was discussed. The risk model consisting of 6 immune checkpoint-related lncRNAs was an independent predictor of survival. Through regrouping the patients with this model, we can distinguish between them more effectively in terms of their immunotherapeutic response, tumour microenvironment, and chemotherapy response. This risk model based on immune checkpoint-based lncRNAs may have an excellent clinical value for predicting the immunotherapeutic response and outcomes of patients with LUAD.

Immune checkpoints related-LncRNAs can identify different subtypes of lung cancer and predict immunotherapy and prognosis.

BACKGROUND: Non-small cell lung cancer is the most common subtype of lung cancer in the world. However, the survival rate of non-small cell lung cancer patients remains low currently. Immune checkpoint and long non-coding RNAs are emerging as critical roles in prognostic significance and the immunotherapeutic response of non-small cell lung cancer. It is critical to discern LncRNAs related with immune checkpoints in patients with Non-small cell lung cancer. METHODS: In this study, immune checkpoint-linked LncRNAs were determined and achieved by the co-expression analysis. Immune checkpoint-linked LncRNAs with noteworthy prognostic value (P < 0.05) gained were next utilized to separate into two cluster by non-negative matrix factorization (NMF). Univariate and a least absolute shrinkage and selection operator were applied to construct an immune checkpoint-linked LncRNAs model. Kaplan-Meier analysis, Gene Set Enrichment Analysis, and the nomogram were utilized to investigate the LncRNAs model. Lastly, the capability immunotherapy and chemotherapy prediction value of this risk model were also estimated. RESULTS: The model consisting of ten immune checkpoint-related LncRNAs was acknowledged to be a self-determining predictor of prognosis. Through regrouping the NSCLC patients by this model, difference between them more efficiently on immunotherapeutic response, tumor microenvironment and chemotherapy response could be discovered. This risk model related to the immune checkpoint-based LncRNAs may have an excellent clinical prediction for prognosis and the immunotherapeutic response in patients with NSCLC. CONCLUSIONS: We performed an integrative analysis of LncRNAs linked with immune checkpoints and emphasized the significance of NSCLC subtypes classification, immune checkpoints related LncRNAs in estimating the tumor microenvironment score, immune cell infiltration of the tumor, immunotherapy, and chemotherapy response.

Cell membrane-coated nanoparticles as peroxidase mimetics for cancer cell targeted detection and therapy.

The development of novel and efficient recognition molecules that can be easily modified by nanomaterials to achieve ultra-sensitive and specific cancer cell analysis is of great significance for its early diagnosis and timely prognosis. Herin, a new nanostructured hybrid based on cell membrane-coated Au cores- ultrathin Pt skins composite nanoparticles (Au@Pt@CM NPs) were developed for in vitro detection and treatment of cancer cells. In this strategy, the Au@Pt NPs acted as the signal transducer, and the cell membrane were used as the cancer-cell recognition tool. The synthesized Au@Pt@CM NPs could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of the hydrogen peroxide and were demonstrated to have excellent peroxidase-like activity. Coated with the source cancer cell membrane, the nanoparticles achieved highly specific self-recognition to the source cell. Therefore, the colorimetric method based on Au@Pt@CM NPs could detect the cancer cells in the linear range from 50 to 100000 cells/mL with a limit of detection of 5 cells/mL, which is much lower than other colorimetric detection methods. Afterwards, the nanoparticles as a mimetic enzyme were used for therapeutics of cancer cells through the ROS-mediated oxidative damage. Due to the change of the redox state in the cells by the Au@Pt@CM NPs, the hybrid can achieve the growth inhibitory effect and the selective killing effect on cancer cells. It can be expected that this novel hybrid membrane coating method will bring new insight into developing targeted nanomaterials for tumor treatment and detection.

Template-Regulated Bimetallic Sulfide Nanozymes with High Specificity and Activity for Visual Colorimetric Detection of Cellular H2O2.

For the past several decades, most of the research studies on nanozymes have been aimed at improving their catalytic activity and diversity; however, developing nanozymes with strong catalytic activity and great specificity remains a challenge. Herein, a simple and efficient template synthesis method was used to synthesize bimetallic sulfide nanoparticles, NiCo2S4 NPs, and prove that they have excellent peroxidase-like activity with good specificity. By regulating polyvinyl pyrrolidone (PVP) and hexadecyl trimethyl ammonium bromide as the templating agent, we have obtained the NiCo2S4 (PVP) NPs with a high Ni/Co ratio, thus exhibiting superior peroxidase activity. In addition, the NiCo2S4 NPs selectively catalyzed and oxidized colorless 3,3,5,5-tetramethylbenzidine (TMB). On being treated with H2O2, TMB turns blue while other substrates did not undergo the oxidation reaction under the same conditions, such as 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium (ABTS) and dopamine. The high specificity of NiCo2S4 NPs is due to the strong electrostatic driving coordination between negatively charged NiCo2S4 NPs and positively charged TMB. Due to the peroxidase activity of the developed NiCo2S4 NPs, a simple, low-cost, and reliable colorimetric method was established. Simultaneously, this method for in situ quantitative monitoring of H2O2 produced by MDA-MB-231 cells was also achieved. This study has provided a theoretical basis for the improvement of the activity and specificity of bimetallic sulfide nanozymes and may offer guidance for the further reasonable design of related materials.

Catalytic amplification based on hierarchical heterogeneity bimetal-organic nanostructures with peroxidase-like activity.

In this paper, integrating heterometallic units and nanostructures into metal-organic frameworks (MOFs) were applied to improve the sensitivity of detecting hydrogen peroxide (H2O2) in neutral solution. The bimetal-MOFs (CuCo-BDC) and GO composite (CuCo-BDC/GO) were first synthesized via an ordinary one-step solvothermal synthesis. The CuCo-BDC/GO with admirable peroxidase-like catalytic activity could be applied to detect H2O2. The results have low detection limit of 69 nM (S/N = 3) and a wide linear detection range, from 100 nM to 3.5 mM. This is superior to recently published biosensors based on noble metal nanomaterials, which confirms CuCo-BDC/GO as the MOF electrocatalysts with high performance. The remarkable electroanalytical performance of CuCo-BDC/GO is due to the presence of numerous open metal active sites, the synergistic effect of Cu2+ and Co2+, hierarchical structure with high-specific surface areas and the marvelous electrochemical properties of GO. Therefore, CuCo-BDC/GO is a powerful candidate for detecting H2O2 in electrochemical biosensing fields. Moreover, H2O2 detection in real samples can be done with the CuCo-BDC/GO, including human serum samples. Therefore, the novel CuCo-BDC/GO is a promising catalyst that can be applied in biotechnological and environmental applications.

Long non-coding RNA DUXAP8 promotes the cell proliferation, migration, and invasion of papillary thyroid carcinoma via miR-223-3p mediated regulation of CXCR4.

Papillary thyroid carcinoma (PTC) is a differentiated type of thyroid malignancy with a high incidence. Long non-coding RNA (lncRNA) DUXAP8 has been reported to participate in the proliferation, migration, and invasion of several cancer types. However, its association with PTC has not yet been reported. The current study aimed to investigate the role of DUXAP8 in PTC and revealed the underlying mechanisms. The expression of DUXAP8 was knocked down in two PTC cell lines and the effects of DUXAP8 on the PTC biological behavior were examined by cell counting kit-8 (CCK-8), wound healing, and transwell invasion assays. Luciferase reporter assay was used to detect the binding activity between miR-223-3p and DUXAP8. We found that knockdown of DUXAP8 inhibited the proliferation, migration, and invasion of PTC cells. DUXAP8 could sponge miR-223-3p through the specific binding site. CXCR4 was a target of miR-223-3p. The malignant phenotypes of the PTC cells were suppressed by the over-expression of miR-223-3p. Moreover, miR-223-3p inhibition or CXCR4 over-expression partly restored the proliferation, migration, and invasion activities of DUXAP8-downregulated PTC cells. The results evidenced that DUXAP8 acted as an oncogene in PTC, these effects seemed to partly dependent on the miR-223-3p/CXCR4 axis.