Tumor cell-released autophagosomes (TRAPs) induce PD-L1-decorated NETs that suppress T-cell function to promote breast cancer pulmonary metastasis.

BACKGROUND: Lung metastasis is the primary cause of breast cancer-related mortality. Neutrophil extracellular traps (NETs) are involved in the progression of breast cancer. However, the mechanism of NET formation is not fully understood. This study posits that tumor cell-released autophagosomes (TRAPs) play a crucial role in this process. METHODS: TRAPs were isolated from breast cancer cell lines to analyze their impact on NET formation in both human and mouse neutrophils. The study used both in vitro and in vivo models, including Toll-like receptor 4 (TLR4-/-) mice and engineered breast cancer cell lines. Immunofluorescence, ELISA, Western blotting, RNA sequencing, and flow cytometry were employed to dissect the signaling pathways leading to NET production and to explore their immunosuppressive effects, particularly focusing on the impact of NETs on T-cell function. The therapeutic potential of targeting TRAP-induced NETs and their immunosuppressive functions was evaluated using DNase I and αPD-L1 antibodies. Clinical relevance was assessed by correlating circulating levels of TRAPs and NETs with lung metastasis in patients with breast cancer. RESULTS: This study showed that TRAPs induced the formation of NETs in both human and mouse neutrophils by using the high mobility group box 1 and activating the TLR4-Myd88-ERK/p38 signaling axis. More importantly, PD-L1 carried by TRAP-induced NETs inhibited T-cell function in vitro and in vivo, thereby contributing to the formation of lung premetastatic niche (PMN) immunosuppression. In contrast, Becn1 KD-4T1 breast tumors with decreased circulating TRAPs in vivo reduced the formation of NETs, which in turn attenuated the immunosuppressive effects in PMN and resulted in a reduction of breast cancer pulmonary metastasis in murine models. Moreover, treatment with αPD-L1 in combination with DNase I that degraded NETs restored T-cell function and significantly reduced tumor metastasis. TRAP levels in the peripheral blood positively correlated with NET levels and lung metastasis in patients with breast cancer. CONCLUSIONS: Our results demonstrate a novel role of TRAPs in the formation of PD-L1-decorated NETs, which may provide a new strategy for early detection and treatment of pulmonary metastasis in patients with breast cancer.

Dual-targeting tigecycline nanoparticles for treating intracranial infections caused by multidrug-resistant Acinetobacter baumannii.

Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood-brain barrier (BBB). In this study, we prepared a novel core-shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aß11 and Tween 80 (Aß11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aß11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation.

KepSalinst: Using Peripheral Points to Delineate Salient Instances.

Salient instance segmentation (SIS) is an emerging field that evolves from salient object detection (SOD), aiming at identifying individual salient instances using segmentation maps. Inspired by the success of dynamic convolutions in segmentation tasks, this article introduces a keypoints-based SIS network (KepSalinst). It employs multiple keypoints, that is, the center and several peripheral points of an instance, as effective geometrical guidance for dynamic convolutions. The features at peripheral points can help roughly delineate the spatial extent of the instance and complement the information inside the central features. To fully exploit the complementary components within these features, we design a differentiated patterns fusion (DPF) module. This ensures that the resulting dynamic convolutional filters formed by these features are sufficiently comprehensive for precise segmentation. Furthermore, we introduce a high-level semantic guided saliency (HSGS) module. This module enhances the perception of saliency by predicting a map for the input image to estimate a saliency score for each segmented instance. On four SIS datasets (ILSO, SOC, SIS10K, and COME15K), our KepSalinst outperforms all previous models qualitatively and quantitatively.

Largemouth bass Rel exerts antiviral role against fish virus and regulates the expression of interleukin-10.

Nuclear factor-κB (NF-κB)/Rel is a group of transcription factors that can be activated and regulates various aspects of innate and adaptive immune functions, which play a crucial role in mediating inflammatory responses. Interleukin-10 (IL-10) is a highly pleiotropic cytokine that has a central role in limiting the immune response to pathogens during infection and thereby alleviating damage to the host. This study aims to investigate the function of the Rel gene in virus infection and its regulatory effect on IL-10 in the largemouth bass (Micropterus salmoides). The ORF sequence of MsRel was 1941 bp, containing 646 amino acids with two conserved functional domains, including RHD and IPT domain. In healthy largemouth bass, the mRNA of MsRel was detected in all the tested tissues, including gill, liver, kidney, heart, spleen, intestine, stomach, skin, brain, fin and muscle. The expression of MsRel was induced by challenge with largemouth bass virus (LMBV) or red grouper nervous necrosis virus (RGNNV), as well as treatment with lipopolysaccharide (LPS) or poly (I:C) in vivo. As evidenced by the detection of viral gene mRNA levels, the infectivity of LMBV and morphological cytopathic effect (CPE), we found that overexpression of MsRel inhibited the infection and replication of LMBV, suggesting its antiviral roles in fish. Besides, the promoter analysis was carried out to determine whether MsRel was a regulator of MsIL-10. The results of the luciferase reporter assay indicated that MsRel has a positive regulatory role in MsIL-10 expression. Further analysis revealed that the potential binding sites of MsIL-10 may be located in the MsIL10-5-M (-42 to +8 bp) region of the MsIL-10 promoter. Furthermore, we observed that MsRel enhanced IFN-I and IFN-III promoter activities. Taken together, our findings demonstrated that MsRel affect LMBV infection by regulating the immune responses, and providing a new idea of the mechanisms how Rel regulate the expression of IL-10 in bony fish.

Natto: A medicinal and edible food with health function.

Natto is a soybean product fermented by natto bacteria. It is rich in a variety of amino acids, vitamins, proteins and active enzymes. It has a number of biological activities, such as thrombolysis, prevention of osteoporosis, antibacterial, anticancer, antioxidant and so on. It is widely used in medicine, health-care food, biocatalysis and other fields. Natto is rich in many pharmacological active substances and has significant medicinal research value. This paper summarizes the pharmacological activities and applications of natto in and outside China, so as to provide references for further research and development of natto.

hsa_circ_0000047 targeting miR-6720-5p/CYB5R2 axis alleviates inflammation and angiogenesis in diabetic retinopathy.

Context: Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM). Circular RNAs (circRNAs) act as key regulators of DR development by regulating inflammation and angiogenesis.Objective: This study aimed to elucidate the function and mechanism of hsa_circ_0000047 in DR.Materials and methods: High glucose (HG) was used to induce human retinal microvascular endothelial cells (hRMECs) to construct a DR model in vitro. Qualitative real-time polymerase chain reaction (qRT-PCR) or western blotting were used to detected the levels of hsa_circ_0000047, miR-6720-5p, and CYB5R2 in DR and HG-indeced hRMECs. Cell functional experiments were performed to detect the change of viability, inflammation, migration, invasion, and angiogenesis of HG-induced hRMECs. Besides, the correlation between miR-6720-5p and hsa_circ_0000047/CYB5R2 was confirmed by luciferase assay and Pearson correlation analysis.Results: hsa_circ_0000047 and CYB5R2 were downregulated in DR, whereas miR-6720-5p was upregulated in DR. Cell functional experiments showed that hsa_circ_0000047 overexpression restrained viability, inflammation, migration, invasion, and angiogenesis of HG-induced hRMECs. Regarding mechanism, hsa_circ_0000047 could sponge miR-6720-5p to regulate CYB5R2 expression in hRMECs. Additionally, CYB5R2 knockdown reversed the effects of hsa_circ_0000047 overexpression on HG-induced hRMECs.Conclusion: Our study revealed that hsa_circ_0000047 alleviated inflammation and angiogenesis in HG-induced hRMECs by targeting the miR-6720-5p/CYB5R2 axis, which may be a novel biomarker for DR therapy.

Interaction Between Dietary Selenium and Zinc Intakes on Hypothyroidism.

This study assessed the independent association of dietary selenium and zinc intakes with the risk of hypothyroidism and interaction effect between dietary selenium and zinc intakes with the risk of hypothyroidism in Americans. The data of this cross-sectional study was from the National Health and Nutritional Examination Survey (NHANES) 2007-2012. The outcome was defined as new-onset hypothyroidism. Weighted univariate and multivariate logistic regression and the subgroup analyses based on gender and body mass index (BMI) were conducted to evaluate the association between the dietary selenium and zinc intakes and new-onset hypothyroidism. Odds ratio (OR) and 95% confidence interval (CI) were calculated. A total of 6402 participants were included with 131 (2.05%) developed a hypothyroidism in this study. Compared with participants with high zinc intake, those with low zinc intake had a higher risk of new-onset hypothyroidism (OR = 1.74, 95% CI: 1.05-2.90). Moreover, we also found a significant interaction between dietary selenium level intake and dietary zinc level intake on new-onset hypothyroidism risk (OR = 5.99, 95% CI: 1.77-20.23). There was an interaction between dietary selenium and zinc intakes on the risk of new-onset hypothyroidism, especially the significant effect for adults with women or overweight. The findings indicated that improving the levels of dietary zinc and selenium intake may be beneficial in preventing of new-onset hypothyroidism.

Hydrogel-Derived Co3ZnC/Co Nanoparticles with Heterojunctions Supported on N-Doped Porous Carbon and Carbon Nanotubes for the Highly Efficient Oxygen Reduction Reaction in Zn-Air Batteries.

It is crucial for metal-air batteries and fuel cells to design non-precious-metal catalysts instead of platinum-based materials to boost the sluggish oxygen reduction reaction (ORR). Herein, Co3ZnC/Co nanoparticles with heterojunctions supported on N-doped porous carbon and carbon nanotubes (CNTs) are fabricated by pyrolyzing the hydrogel prepared from melamine and citric acid chelated with Co2+/Zn2+ ions. This hybrid shows strong ORR catalytic activity as its half-wave potential reaches 0.88 V (vs reversible hydrogen electrode (RHE)) in 0.1 M KOH and Zn-air batteries with the catalyst have higher discharge plateaus and capacity than those employing Pt/C. The hybrid mixed with RuO2 can also be used as an efficient bifunctional catalyst for rechargeable Zn-air batteries. The excellent performance is primarily derived from the Co3ZnC/Co heterojunctions, the electron transfer of which boosts the ORR catalysis. Moreover, the suitable ratio of Co/Zn in precursors results in the epitaxial growth of hollow CNTs and abundant mesopores, hence promoting the adsorption of oxygen and the transport of ORR-related species.

Grouper ATF1 plays an antiviral role in response to iridovirus and nodavirus infection.

Transcription factor ATF1 is a member of the ATF/CREB family of the CREB subfamily and is involved in physiological processes such as tumorigenesis, organ development, reproduction, cell survival, and apoptosis in mammals. However, studies on ATF1 in fish have been relatively poorly reported, especially on its role in antiviral immunity in fish. In this study, ATF1 from orange-spotted grouper (named EcATF1) were cloned and characterized. Molecular characterization analysis showed that EcATF1 encodes a 307-amino-acid protein, containing PKID and bZIP_CREB1 domains. Homology analysis showed that had the highest homology with E. lanceolatus(88.93%). Tissue expression pattern showed that EcATF1 was extensively distributed in twelve selected tissues, with higher expression in the skin, gill, liver and spleen. Subcellular localization analysis showed that EcATF1 was distributed in the nucleus of GS cells. EcATF1 overexpression inhibits Singapore grouper iridovirus (SGIV) and red-spotted grouper nervous necrosis virus (RGNNV) replication, as evidenced by a diminished degree of CPE induced by SGIV and RGNNV and a reduction in the level of viral gene transcription and viral capsid protein expression. Furthermore, EcATF1 overexpression upregulated interferon pathway-related genes and proinflammatory factors, and increased the promoter activities of IFN, IFN stimulated response element (ISRE), and nuclear factor κB(NFκB). Meanwhile, EcATF1 overexpression positive regulate the MHC-I signaling pathway, and upregulated the promoter activity of MHC-I. Collectively, these data demonstrate that EcATF1 plays an important role during the host antiviral immune response. This study provides insights into the function of ATF1 in the immune system of lower vertebrates.

Studies on Quality Markers of Kaihoujian Spray for Anti-Inflammation Based on Gray Correlation Analysis Strategy.

Kaihoujian spray (KHJ) was originated from the classical prescription of Miao medicine, which was commonly used for acute and chronic pharyngitis. The prescription was composed of Sophorae Tonkinensis Radix, Ardisiae Radix, Cicadae Periostracum, and menthol. However, in previous literature, only clinical studies have been reported. The Quality Marker (Q-Markers) of KHJ on anti-inflammation has not been clearly elucidated. In this study, a gray correlation analysis strategy combined with network pharmacology analysis was established for the investigation of Q-Markers in KHJ. A total of 52 components were identified or tentatively characterized in KHJ, including alkaloids, saponins, bergenin, flavonoids, amino acids, and their derivatives. Furthermore, regularity of recipe composition and gray correlation analysis revealed that the correlation degree of all peaks was greater than 0.5. The ranking of correlation degree was peak 1 > 6>9 > 8>7 > 10>4 > 5>11 > 3>2. Among them, peaks 2, 4, 5, 6, 8, 9, and 11 were identified as anagyrine, matrine, sophocarpine, norbergenin, bengenin, 11-O-galloylbergenin, and trifolirhizin. The network pharmacology analysis revealed that EGFR, MMP9, MMP3, MMP1, and PTGS2 were the main targets of KHJ. Bergenin, matrine, sophocarpine, calycosin, and trifolirhizin were the main anti-inflammatory active ingredient in KHJ. These results proposed that bergenin, sophocarpidine, sophocarpine, and trifolirhizin could be the Q-Markers of KHJ on anti-inflammation. The process of discovering the Q-Markers would provide a promising method of quality control on KHJ.

The transcription factor RFX5 positively regulates expression of MHCIa in the red-spotted grouper (Epinephelus akaara).

Regulatory factor X 5 (RFX 5) is a member of the RFX family, and it forms the transcription factor complex RFX with RFXANK/B and RFXAP. The RFX complex can activate MHC expression by binding to the MHC promoter. However, the regulate mechanism of RFX in fish species is not been fully elucidated. In this study, we investigated the transcriptional regulation of Epinephelus akaara RFX5 (EaRFX5) on EaMHCI, and its effect on immune pathways. The genomic sequence of EaRFX5 was 35,774 bp and consisted of ten exons and nine introns. The length of EaRFX5 ORF sequence is 2,160 bp, encoding 719 amino acids. By qRT-PCR, EaRFX5 was detected constitutively expressed in twelve selected tissues, showing a wide range of expression. EaRFX5 expression parttern in response to poly (I:C), LPS, Zymosan A, SGIV, and NNV challenges showed that EaRFX5 plays a differentiated immunomodulatory role in response to various stimuli in different tissues, and EaRFX5 was most significantly upregulated in the kidney after challenge with SGIV. Subcellular localization assays showed that EaRFX5 is a typical nuclear protein. Based on the in vitro overexpression experiments, EaRFX5 appeared to promote the expression of EaMHCIa gene, interferon signalling pathway and inflammatory cytokine. Luciferase reporter assay showed that the -267 bp to +82 bp region of EaMHCIa promoter was the core region where EaRFX5 modulated. Additionally, point mutations and electrophoretic mobility shift assays indicating M3 is the EaRFX5 binding sites in the EaMHCIa promoter. These results contribute to elucidating the function of EaRFX5 in fish immune response, and provide the first evidence of positive regulation of MHCIa expression by RFX5 in fish.

Functional analysis of a novel MHC-Iα genotype in orange-spotted grouper: Effects on Singapore grouper iridovirus (SGIV) replication and apoptosis.

The classical major histocompatibility complex class I (MHC-Ⅰ) molecule plays a key role in vertebrate immune response for its important functions in antigen presentation and immune regulation. MHC pathway is closely related to many diseases involving autoimmunity, antigen intrusion and inflammation. However, rare literatures about the effect of MHC-I on fish cells apoptosis were reported. In this study, a novel type of MHC-Ⅰα genotype from orange-spotted grouper (named EcMHC-ⅠA*01) were cloned and characterized. It shared a 77% identity to its Epinephelus coioides MHC-Iα homology that has been uploaded to NCBI (ACZ97571.1). Molecular characterization analysis showed that EcMHC-ⅠA*01 encodes a 357-amino-acid protein, containing a signal peptide，α1，α2，α3, Cytoplasmic (Cyt) and Transmembrane (TM) domains. Tissue expression pattern showed that EcMHC-ⅠA*01 was extensively distributed in twelve selected tissues, with higher expression in the gill, intestine and skin. The expression of EcMHC-ⅠA*01 in grouper liver and spleen tissues were significantly induced by different stimuli (Zymosan A, LPS, Ploy I:C, RGNNV and SGIV). Comparing with the EcMHC-ⅠA*01 expression levels induced by Zymosan A, Ploy I:C and RGNNV, the effects induced by SGIV and LPS were more significant. Subcellular localization analysis showed that EcMHC-ⅠA*01 localizes throughout the cytoplasm appeared both diffuse and focal intracellular expression pattern. Overexpression of EcMHC-ⅠA*01 inhibited the CPE progression, the mRNA expression of the SGIV related genes (MCP, LITAF, ICP-18 and VP19) and the protein expression of MCP. Meanwhile, qRT-PCR result showed that EcMHC-ⅠA*01 overexpression upregulated the expression of interferon signaling molecules (IFN-γ, ISG56, MDA5 and MXI) and inflammatory cytokines (IL-1ß, IL-6, TNF-α and TRAF6). In addition, our results showed that overexpression of EcMHC-ⅠA*01 promoted the apoptosis of normal fathead minnow (FHM) cells as well as the apoptosis of FHM cells induced by SGIV. However, there was no significant change in the activity of caspase 3 between control group and EcMHC-ⅠA*01 overexpression group, suggesting that EcMHC-ⅠA*01-induced apoptosis may not depend on the caspase 3 pathway. Taken together, these data in our study provide new insights into the role of MHC-I in antiviral immune response and apoptosis in fish.

The transcription factor NFYC positively regulates expression of MHCIa in the red-spotted grouper (Epinephelus akaara).

Mammalian studies have shown that the nuclear transcription factor Y (NFYC) regulates the expression of major histocompatibility complex (MHC) by binding to CCAAT-box on promoters. However, few studies have focused on the regulatory mechanisms of NFYC in MHC pathway in fish. To explore the transcriptional regulatory mechanism of MHCIa in fish, we characterized NFYC and MHCIa of red-spotted grouper (Epinephelus akaara) (named EaNFYC and EaMHCIa, respectively). The EaNFYC genome sequence is 13,796 bp and contains 1,065 bp open reading frame. It is composed of ten exons and nine introns and encode a 354 amino acid sequence. The putative EaNFYC protein sequence shared 67.2-99.4% identity to vertebrate NFYC and possesses a typically conserved domain (histone- or haem-associated protein 5 domain (HAP5)) at the N-terminus. Transcripts of both EaNFYC and EaMHCIa were ubiquitously expressed in all detect tissues, and higher mRNA levels were detected in immune-relevant tissues (middle-kidney). EaNFYC expression increased after treatment with polyinosinic: polycytidylic acid, lipopolysaccharide, nervous necrosis virus, zymosan A, and Singapore grouper iridovirus. Analysis of subcellular localization indicated that EaNFYC was localized at the cell nucleus only. Furthermore, overexpression of EaNFYC significantly stimulated the expression of EaMHCIa, interferon signalling molecules and inflammatory cytokine. The region -878 bp to +82 bp of EaMHCIa promoter was identified to be the core promoter which EaNFYC take effect on. Additionally, point mutations and electrophoretic mobility shift assays verified that NFYC activate MHCIa expression by binding at the M1 and M2 binding sites that do not contain CCAAT-box. These results contribute to elucidating the function of fish NFYC on MHC transcriptional mechanisms, and provide the first evidence of positive regulation of MHCIa expression by NFYC in fish.

Identification and verification of microRNA signature and key genes in the development of osteosarcoma with lung metastasis.

BACKGROUND: Osteosarcoma (OS) is a heterogeneous malignant spindle cell tumor in children under the age of 20. This study aims to research the association between Solute Carrier Family 7 Member 8 (SLC7A8) as well as related genes and OS. METHOD: OS and normal samples (GSE38698 and GSE85537) were downloaded from Gene Expression Omnibus dataset. The bioinformatics analysis was performed to distinguish 2 differentially expressed genes, prognostic candidate genes and functional enrichment pathway. Immunohistochemistry and quantitative real-time PCR were utilized for further study. RESULTS: There were 5 DEMs and 10 differentially expressed genes in cancer tissues compared to normal tissues. According to the km-plot software, ARHGEF3, BSN, PQLC3, and SLC7A8 were significantly related to the overall survival of patients with OS. Furthermore, Multivariate analysis included that SLC7A8 was independent risk factors for OS patients. Furthermore, immunohistochemistry and quantitative real-time PCR outcomes indicated that the expression level of SLC7A8 and hsa-miR-506 was differentially expressed in lung metastasis OS tissues and non-metastasis tissues. CONCLUSION: The prognostic model based on the miRNA-mRNA network could provide predictive significance for prognosis of OS patients, which would be worthy of clinical application. Our results concluded that SLC7A8 may play a key role in the development of OS.

The complete mitochondrial genome of two-belt cardinal and striped cardinalfish Apogonichthyoides taeniatus (Cuvier, 1828).

The complete mitochondrial DNA sequence of Apogonichthyoides taeniatus (Cuvier, 1828) is determined. The mitochondrial genome is 17,050 in length and has the same composition and gene order like most other vertebrates. The phylogenetic analysis based on 13 concatenated PCGs nucleotide sequences among 20 species showed that this species has high support with the sister branch Jaydia lineata. Our findings provide useful information for phylogenetic and evolutionary research of Kurtiformes species.

Flavonoid glycosides from the fruits of Embelia ribes and their anti-oxidant and α-glucosidase inhibitory activities.

Three new flavonoid glycosides, embeliaflavosides A-C (1-3), together with eight known flavonoid glycosides (4-11), were isolated from the fruits of Embelia ribes. Their structures were established based on the analyses of spectroscopic data. Compounds 1-11 were evaluated for antioxidant and α-glucosidase inhibitory activities. The results revealed that compounds 1-11 owned significant ABTS radical scavenging activity with IC50 values of 2.52-9.78 µM, and DPPH scavenging activity with IC50 values of 7.56-26.47 µM, respectively. However, α-glucosidase inhibition assay indicated that all the isolates were inactive.[Formula: see text].

Electrocatalytic, Kinetic, and Mechanism Insights into the Oxygen-Reduction Catalyzed Based on the Biomass-Derived FeOx @N-Doped Porous Carbon Composites.

A valid strategy for amplifying the oxygen reduction reaction (ORR) efficiency of non-noble electrocatalyst in both alkaline and acid electrolytes by decorated with a layer of biomass derivative nitrogen-doped carbon (NPC) is proposed. Herein, a top-down strategy for the generally fabricating NPC matrix decorated with trace of metal oxides nanoparticles (FeOx NPs) by a dual-template assisted high-temperature pyrolysis process is reported. A high-activity FeOx /FeNC (namely Hemin/NPC-900) ORR electrocatalyst is prepared via simply carbonizing the admixture of Mg5 (OH)2 (CO3 )4 and NaCl as dual-templates, melamine and acorn shells as nitrogen and carbon source, hemin as a natural iron and nitrogen source, respectively. Owing to its unique 3D porous construction, large BET areas (819.1 m2 ∙g-1 ), and evenly dispersed active sites (FeNx , CN, and FeO parts), the optimized Hemin/NPC-900 catalyst displays comparable ORR catalytic activities, remarkable survivability to methanol, and preferable long-term stability in both alkali and acid electrolyte compared with benchmark Pt/C. More importantly, density function theory computations certify that the interaction between Fe3 O4 nanoparticles and arm-GN (graphitic N at armchair edge) active sites can effectually promote ORR electrocatalytic performance by a lower overpotential of 0.81 eV. Accordingly, the research provides some insight into design of low-cost non-precious metal ORR catalysts in theory and practice.

Identification of candidate SNPs and genes associated with anti-RGNNV using GWAS in the red-spotted grouper, Epinephelus akaara.

The red-spotted grouper, Epinephelus akaara, has been cultured widely in China, and in several countries of Southeast Asia, due to its important economic value. However, in recent years the outbreak of disease caused by red-spotted grouper nervous necrosis virus (RGNNV) has caused mass mortality in the stage of the grouper lifecycle from fry to juvenile, resulting in considerable economic loss in commercial aquaculture. However, the molecular mechanism underlying anti-RGNNV infection in red-spotted grouper has never been fully understood. To identify the anti-RGNNV related markers and candidate genes, we performed a genome-wide association study (GWAS) on a natural population of 100 individuals for a full-genome screen of the red-spotted grouper. In this research, 36,311 single, high quality nucleotide polymorphisms (SNPs) were developed. Two significantly associated SNPs and three suggestively associated SNPs were identified at the genome level. From these identified SNPs, five candidate genes were annotated: EPHA7, Osbpl2, GPC5, CDH4 and Pou3f1. These genes are involved in nervous system development, retinal formation, and lipid metabolism regulation. In combination with studies on the characteristics of NNV infection, it was speculated that in the fry stage of the grouper lifecycle, the immune system is not fully developed. Therefore, improved resistance to RGNNV may come through regulating nervous system development or lipid metabolism related pathways. In addition, the genotypes of SNPs associated with disease-resistant traits were analyzed. The markers and genes obtained in this study may facilitate a marker-assisted selection for red-spotted grouper aiming at disease resistance to RGNNV.

Long non-coding RNA MEG3 inhibits neovascularization in diabetic retinopathy by regulating microRNA miR-6720-5p and cytochrome B5 reductase 2.

Diabetic retinopathy (DR) is a major cause of vision loss in working and elderly populations. long non-coding RNA (LncRNA) MEG3 is thought to have some effect on DR, but the exact mechanism remains to be clarified. The expression levels of lncRNA MEG3, miR-6720-5p, and cytochrome B5 reductase 2 (CYB5R2) in human retinal microvascular endothelial cells (hRMECs) were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell migration, and tube formation assays were used to determine the cell viability, migration, and tube formation ability of hRMECs, respectively. The interaction of MEG3, miR-6720-5p, and CYB5R2 was detected and explored by a luciferase assay. The expression of MEG3 and CYB5R2 was upregulated and that of miR-6720-5p was downregulated in patients with DR and hRMECs treated with high glucose. Knocking down MEG3 or CYB5R2 promoted proliferation, migration, and neovascularization in hRMECs. The intervention of miR-6720-5p reversed the effect of MEG3 knockdown on hRMEC function, and this effect was eliminated by silencing CYB5R2. Therefore, MEG3 acted as a sponge to suppress miR-6720-5p and regulate the expression of CYB5R2, thereby inhibiting DR neovascularization.

Resolvin D2 prevents inflammation and oxidative stress in the retina of streptozocin-induced diabetic mice.

Diabetic retinopathy is the main ocular complication of diabetes mellitus. The aim of this study was to investigate the protective effect and mechanism of resolvin D2 (RvD2) on diabetic retinopathy. Streptozocin-induced C57/BJ diabetic mice were divided into three groups: normal control, diabetes mellitus, and diabetes plus RvD2 treatment. After three months of diabetic model induction, exogenous RvD2 was injected, monthly for three months, into the vitreous cavity of mice in the diabetic treatment group. Retinal vascular leakage, ganglion cell apoptosis, inflammatory factor expression, and oxidative stress factors were detected one month after the last injection. The levels of retinal vascular leakage and ganglion cell apoptosis in diabetic mice treated with RvD2 were significantly lower than those in untreated diabetic mice, as were the retinal levels of inflammatory factors and oxidative stress. In conclusion, RvD2 might be used as a retinal protective factor for diabetes mellitus by reducing inflammation and oxidative stress.