Prognostic Value and Clinical Significance of Vesicular Transport-Related Genes in Clear Cell Renal Cell Carcinoma.

INTRODUCTION: Vesicular transport (VT) has a complex relationship with tumor progression and immunity. But prognostic significance of VT in clear cell renal cell carcinoma (ccRCC) is unclear. Thus, we aimed to establish a prognostic model according to VT to predict overall survival of ccRCC patients. METHODS: We used patient data from TCGA database and built a prognostic model with 13 VT-related genes (VTRGs) by differential expression analysis, LASSO regression, and univariate/multivariate Cox analysis. The model was validated internally and externally, and survival analysis and ROC curves depicted excellent predictive ability. Furthermore, higher modeled riskscores corresponded to more advanced tumor progression. To further understand the potential reasons for different prognoses in patients, we did enrichment analysis on differentially expressed genes identified by the model in risk groups. The expression levels and roles of SAA1 and KIF18B in ccRCC were verified by qRT-PCR and cell function experiments. RESULTS: Humoral immune response and cAMP signaling pathway may be the biological processes and pathways leading to poor prognosis. Further analysis of immune microenvironment presented that ccRCC patients with poor prognoses had highly immune-infiltrated characteristics. We compared the drug response data of samples from different prognostic patients in the GDSC database and identified drug sensitivity differences associated with prognosis. Finally, we demonstrated that SAA1 and KIF18B could increase the proliferation, migration, and invasion ability of ccRCC cells using cellular experiments. CONCLUSION: In summary, we further revealed the importance of VTRGs in ccRCC prognosis.

Regulating the Topology of Covalent Organic Frameworks for Boosting Overall H2O2 Photogeneration.

Photocatalytic oxygen reduction reactions and water oxidation reactions are extremely promising green approaches for massive H2O2 production. Nonetheless, constructing effective photocatalysts for H2O2 generation is critical and still challenging. Since the network topology has significant impacts on the electronic properties of two dimensional (2D) polymers, herein, for the first time, we regulated the H2O2 photosynthetic activity of 2D covalent organic frameworks (COFs) by topology. Through designing the linking sites of the monomers, we synthesized a pair of novel COFs with similar chemical components on the backbones but distinct topologies. Without sacrificial agents, TBD-COF with cpt topology exhibited superior H2O2 photoproduction performance (6085 and 5448 µmol g-1 h-1 in O2 and air) than TBC-COF with hcb topology through the O2-O2⋅--H2O2, O2-O2⋅--O2 1-H2O2, and H2O-H2O2 three paths. Further experimental and theoretical investigations confirmed that during the H2O2 photosynthetic process, the charge carrier separation efficiency, O2⋅- generation and conversion, and the energy barrier of the rate determination steps in the three channels, related to the formation of *OOH, *O2 1, and *OH, can be well tuned by the topology of COFs. The current study enlightens the fabrication of high-performance photocatalysts for H2O2 production by topological structure modulation.

Complete genome sequence of a novel double-stranded RNA virus infecting the phytopathogenic fungus Rhizopus stolonifer.

In this study, we report the complete genome sequence of a novel toti-like virus, tentatively named "Rhizopus stolonifer double-stranded RNA virus 1" (RsDSV1), identified from a phytopathogenic fungal agent of apple fruit rot disease, Rhizopus stolonifer strain A2-1. RsDSV1 has a double-stranded RNA genome. The complete RsDSV1 genome is 5178 nucleotides (nt) in length and contains two open reading frames (ORFs) encoding a putative coat protein (CP) and an RNA-dependent RNA polymerase (RdRp). Phylogenetic analysis based on RdRp and CP amino acid sequences revealed that RsDSV1 is closely related to unclassified members of the family Totiviridae. In stress-inducing Vogel's minimal and sodium dodecyl sulfate-containing media, hyphal growth of A2-1 was suppressed, but the accumulation of RsDSV1 RNA increased, indicating that stresses promote RsDSV1 replication. To our knowledge, this is the first report of a mycovirus found in R. stolonifer.

Complete genome sequence of a novel ourmia-like mycovirus infecting the phytopathogenic fungus Botryosphaeria dothidea.

Here, we describe the full-length genome sequence of a novel ourmia-like mycovirus, tentatively named "Botryosphaeria dothidea ourmia-like virus 1" (BdOLV1), isolated from the phytopathogenic fungus Botryosphaeria dothidea strain 8A, associated with apple ring rot in Shanxi province, China. The complete BdOLV1 genome is comprised of a 2797-nucleotide positive-sense (+) single-stranded RNA (ssRNA) with a single open reading frame (ORF). The ORF putatively encodes a 642-amino-acid polypeptide with conserved RNA-dependent RNA polymerase (RdRp) motifs related to those of viruses of the family Botourmiaviridae. Phylogenetic analysis based on RdRp amino acid sequences showed that BdOLV1 is grouped with unclassified oomycete-infecting viruses closely related to members of the genus Botoulivirus in the family Botourmiaviridae. This is the first report of a novel (+)ssRNA virus in B. dothidea related to members of the genus Botoulivirus in the family Botourmiaviridae.

The effect of Epigallocatechin-3-gallate on small intestinal morphology, antioxidant capacity and anti-inflammatory effect in heat-stressed broilers.

This study was to investigate the effects of Epigallocatechin-3-gallate (EGCG) on intestinal morphology, antioxidant capacity and anti-inflammatory response in heat-stressed broiler. A total of 192 2-week-old Arbour Acres broilers chickens were divided into four groups with six replicates per group and eight chickens per replicate: one thermoneutral control group (28°C, group TN), which was fed the basal diet; and three cyclic high-temperature groups (35°C from 7:00 to 19:00 hr; 28°C from 19:00 hr to 7:00 hr, heat stress group), which were fed the basal diet supplementation with EGCG 0 mg/kg (group HS0), 300 mg/kg (group HS300) and 600 mg/kg (group HS600). The gut morphology and intestinal mucosal oxidative stress indicators, as well as intestinal barrier-related gene expression, were analysed. The results showed that compared with group TN, heat stress reduced the villus height (VH), activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD)and catalase (CAT), increased the crypt depth (CD) and malondialdehyde (MDA)content at 21, 28 and 35 days (p < 0.05). After the heat-stressed broilers were supplemented with EGCG, VH, VH/CD (V/C), and the activities of GSH-Px, SOD and CAT were increased, and CD and MDA content were reduced compared with those in group HS0 without EGCG supplementation at 21, 28 and 35 days (p < 0.05). The EGCG supplementation promoted the gene expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), Claudin-1, Mucin 2 (Muc2) and alleviated the nuclear factor-kappa B (NF-κB) and lipopolysaccharide-induced tumour necrosis factor (LITAF) gene expression compared with group HS0 (p < 0.05). Moreover, intestinal morphology was strongly correlated with antioxidant ability and inflammatory response. In conclusion, EGCG alleviated the gut oxidative injury of heat-stressed broilers by enhancing antioxidant capacity and inhibiting inflammatory response.

Effect of epigallocatechin gallate on growth performance and antioxidant capacity in heat-stressed broilers.

This study investigated the effects of epigallocatechin gallate (EGCG) on the growth performance and antioxidant capacity of 35-d-old broilers exposed to heat stress. Broilers, 14 d of age, were divided into four groups with six replicates per group (eight chickens/replicate). Thermoneutral group (Group TN) was fed the basal diet and maintained at 28°C for 24 h/d. The heat-stressed groups were housed at 35°C for 12 h/d and 28°C for 12 h/d and fed the basal diet supplemented with EGCG at 0, 300 and 600 mg/kg diet (Groups HS0, HS 300 and HS600, respectively). Compared with Group TN, heat-stressed groups showed significantly reduced gain, feed intake and serum total protein and glucose levels; inhibited serum alkaline phosphatase activities; and increased serum levels of uric acid, cholesterol and triglycerides and the activity of serum creatine kinase, lactate dehydrogenase and aspartate aminotransferase (p < 0.05). Compared with Group HS0, Group HS600 exhibited an increased gain and feed intake; and normalised blood parameters and enzyme activities. Compared with Group TN, the expression of antioxidant-related liver proteins was decreased in Group HS0 and increased in Groups HS300 and HS600 (p < 0.05). The results suggest that EGCG can improve the growth performance and alleviate the oxidant damage by modulating the antioxidant properties of broilers.

Natural Cross-Kingdom Spread of Apple Scar Skin Viroid from Apple Trees to Fungi.

Viroids are the smallest known infectious agents that are thought to only infect plants. Here, we reveal that several species of plant pathogenic fungi that were isolated from apple trees infected with apple scar skin viroid (ASSVd) carried ASSVd naturally. This finding indicates the spread of viroids to fungi under natural conditions and further suggests the possible existence of mycoviroids in nature. A total of 117 fungal isolates were isolated from ASSVd-infected apple trees, with the majority (85.5%) being an ascomycete Alternaria alternata and the remaining isolates being other plant-pathogenic or -endophytic fungi. Out of the examined samples, viroids were detected in 81 isolates (69.2%) including A. alternata as well as other fungal species. The phenotypic comparison of ASSVd-free specimens developed by single-spore isolation and ASSVd-infected fungal isogenic lines showed that ASSVd affected the growth and pathogenicity of certain fungal species. ASSVd confers hypovirulence on ascomycete Epicoccum nigrum. The mycobiome analysis of apple tree-associated fungi showed that ASSVd infection did not generally affect the diversity and structure of fungal communities but specifically increased the abundance of Alternaria species. Taken together, these data reveal the occurrence of the natural spread of viroids to plants; additionally, as an integral component of the ecosystem, viroids may affect the abundance of certain fungal species in plants. Moreover, this study provides further evidence that viroid infection could induce symptoms in certain filamentous fungi.

Effect of epigallocatechin gallate on growth performance and serum biochemical metabolites in heat-stressed broilers.

This study aims to investigate the effects of epigallocatechin gallate (EGCG) on the growth performance and serum metabolic characteristics of heat-stressed broilers. A total of 192 14-day-old Arbor Acres broilers were divided into 4 groups with 6 replicates per group (8 chickens/cage). Thermoneutral group (Group TN) was fed the basal diet and maintained at 28°C for 24 h/d. The heat-stressed groups were housed at 35°C for 12 h/d and 28°C for 12 h/d and fed the basal diet supplemented with EGCG at 0, 300, and 600 mg/kg diet (Groups HS0, HS300, and HS600, respectively). The production performance and serum metabolic characteristics were analyzed at d 21, 28, and 35, respectively. At d 35 of age, heat stress reduced (P < 0.05) the body weight (BW), feed intake (FI) and the contents of serum total protein (TP) and glucose (GLU); inhibited (P < 0.05) alkaline phosphatase (ALP) activity; But increased (P < 0.05) the contents of uric acid (UA), cholesterol (CHOL), triglyceride (TG), and the activities of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST). Heat-stressed chickens fed EGCG exhibited a linear increase (P < 0.05) in BW, FI, the levels of serum TP, GLU, and ALP activity; and linear decrease (P < 0.05) in the contents of serum UA, CHOL, and TG, as well as the activities of LDH, CK, and AST. Heat stress also reduced (P < 0.05) the activities of serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) on d 35 and increased (P < 0.05) the GSH-Px and SOD activity on d 21 and malondialdehyde (MDA) contents. There was a linear increase (P < 0.05) in activities of GSH-Px, SOD and CAT at 35 d of age, and linear decreased (P < 0.05) in MDA contents. In conclusion, EGCG can improve the growth performance of broilers by enhancing antioxidant property and alleviating oxidant damage caused by heat stress.