From acidity to sweetness: a comprehensive review of carbon accumulation in grape berries.

Most of the carbon found in fruits at harvest is imported by the phloem. Imported carbon provide the material needed for the accumulation of sugars, organic acids, secondary compounds, in addition to the material needed for the synthesis of cell walls. The accumulation of sugars during fruit development influences not only sweetness but also various parameters controlling fruit composition (fruit "quality"). The accumulation of organic acids and sugar in grape berry flesh cells is a key process for berry development and ripening. The present review presents an update of the research on grape berry development, anatomical structure, sugar and acid metabolism, sugar transporters, and regulatory factors.

Dihydropyrimidine Dehydrogenase (DPD) as a Bridge between the Immune Microenvironment of Colon Cancers and 5-FU Resistance.

BACKGROUND: The purpose of the present study was to investigate the role of the 5-Fluorouracil (5-FU) resistance-related factor dihydropyrimidine dehydrogenase (DPD) in tumor immunity and prognosis and to study the relationship between drug resistance and the immune microenvironment of colon cancer. METHODS: Bioinformatics methods were used to analyze the expression of DPD associated with prognosis, immunity, microsatellite instability, and tumor mutational burden in colon cancer. Immunohistochemistry (IHC) was used to detect DPD, MLH1, MSH2, MSH6, and PMS2 in 219 colon cancer tissue samples. Additional IHC analyses were conducted to detect CD4, CD8, CD20, and CD163 in 30 colon cancer tissue samples with the most extensive immune infiltration. The significance of the correlations and clinical significance of DPD with immune infiltration, immune-related markers, microsatellite instability-related indicators, and prognosis were evaluated. RESULTS: The major findings of the present study are as follows: (1) DPD was expressed in tumor and immune cells and associated with certain immune cell-related markers, particularly M2 macrophages that expressed CD163. (2) DPD expression significantly and positively correlated with immune cell markers and immune checkpoints PD-1 and PD-L1. High expression of DPD in immune cells, but not tumor cells, led to increased immune infiltration. (3) High expression of DPD in immune and tumor cells induced 5-FU resistance and was associated with unfavorable prognosis. (4) DPD expression closely correlated with microsatellite instability and tumor mutational burden and led to resistance to 5-FU in patients with microsatellite instability. (5) Bioinformatics analyses revealed that DPD was enriched in immune-related functions and pathways such as activation of T cells and macrophages. CONCLUSIONS: DPD plays an important role in the immune microenvironment and drug resistance of colon cancers and their functional association.

Glutathione peroxidase 2: A key factor in the development of microsatellite instability in colon cancer.

BACKGROUND: Much research has focused on detecting microsatellite instability (MSI), which is frequently employed in the diagnosis and treatment of patients with colon cancer. However, the causes and progression of MSI in colon cancer have not yet been thoroughly elucidated. In this study, we screened and validated the genes associated with MSI in colorectal adenocarcinoma (COAD) using bioinformatics analysis. METHODS: MSI-related genes of COAD were obtained from the Gene Expression Omnibus dataset, Search Tool for the Retrieval of Interaction Gene/Proteins, Gene Set Enrichment Analysis, and Human Protein Atlas. The function, prognostic value, and immune connection of MSI-related genes in COAD were examined using Cytoscape 3.9.1, the Human Gene Database, and the Tumor IMmune Estimation Resource. Key genes were verified using The Cancer Genome Atlas database and immunohistochemistry of clinical tumor samples. RESULTS: We identified 59 MSI-related genes in patients with colon cancer. The protein interaction network of these genes was developed, and numerous functional modules associated with MSI were discovered. Pathways related to MSI were identified using KEGG enrichment analysis, and these included chemokine signaling, thyroid hormone synthesis, cytokine receptor interaction, estrogen signaling, and Wnt signaling pathways. Further analyses were used to identify the MSI-related gene, glutathione peroxidase 2 (GPX2), which was closely related to the occurrence of COAD and tumor immunity. CONCLUSIONS: In COAD, GPX2 may be crucial for the establishment of MSI and tumor immunity, and its deficiency may result in MSI and immune cell infiltration in colon cancer.

The emerging double-edged sword role of Sirtuins in the gastric inflammation-carcinoma sequence revealed by bulk and single-cell transcriptomes.

Histone modification and the inflammation-carcinoma sequence (ICS) have been acknowledgedly implicated in gastric carcinogenesis. However, the extremum expression of some histone modification genes (HMGs) in intestinal metaplasia (IM) rather than GC obscures the roles of HMGs in ICS. In this study, we assumed an explanation that the roles of HMGs in ICS were stage specific. Bulk RNA-seq on endoscopy biopsy samples from a total of 50 patients was accompanied by reanalysis of a set of published single-cell transcriptomes, which cross-sectionally profiled the transcriptomic features of chronic superficial gastritis (SG), atrophy gastritis (AG), IM, and early gastric cancer (GC). Differential analysis observed significantly peaked expression of SIRT6 and SIRT7 at IM. Weighted correlation network analysis on bulk transcriptome recognized significant correlations between SIRT1/6 and IM. The single-cell atlas identified one subgroup of B cells expressing high level of TFF1 (TFF1 hi naive B cell) that theoretically played important roles in defending microbial infection, while SIRT6 displayed a positive correlation with TFF1 low naive B cells. Moreover, gene set enrichment analysis at different lesions (SG-AG, AG-IM, and IM-GC) highlighted that gene sets contributing to IM, e.g., Brush Border, were largely enriched from co-expressing genes of Sirtuins (SIRTs) in AG-IM. Surveys of the genes negatively correlated with SIRT6 in public databases considered SIRT6 as tumor suppressors, which was confirmed by the cell proliferation and migration assays after transient transfection of SIRT6 overexpression vector into AGS cells. All the above observations were then confirmed by serial section-based immunohistochemistry against Ki-67, MUC2, MUC5AC, p53, and SIRT6 on the endoscopic submucosal dissection tissue. By contrast, the expression of the other HMGs varied even opposite within same family. Taken together, this study preliminarily demonstrated the two-edged sword role of SIRTs in ICS and, by extension, showed that the roles of HMGs in ICS were probably stage specific. Our study may provide new insights into and attract attention on gastric prevention and therapy targeting HMGs.

A common tumor in an uncommon site: epithelioid Leiomyoma arising from the seminal vesicle-a case report.

BACKGROUND: Leiomyoma of the seminal vesicle is a rare leiomyoma characterized by the formation of benign leiomyomatous tissue within the seminal vesicle. Although histologically benign, excessive size can lead to urinary system disease if left untreated. Herein, we report a case of a seminal vesicle epithelioid leiomyoma. CASE PRESENTATION: A 36-year-old Chinese man sought medical attention at our hospital for urination pain and hemospermia. CT showed a 5.3 cm × 5.0 cm seminal vesicle mass with a mixed density in the right seminal vesicle. The gross specimen showed light yellow, gray, and white tissues, with softness and hemorrhage in some places. Histologically, it showed classic spindle cell proliferation, with spindle cells arranged in fascicles, and mitosis was rare. Immunohistochemistry showed frequent expression of smooth muscle markers, such as calponin, SMA, and desmin. A diagnosis of epithelioid leiomyoma was proposed according to the immunohistochemical findings and morphology. The patient did not receive adjuvant therapy. There was no evidence of tumor recurrence in the 10 months after surgery. CONCLUSIONS: We report the first case of epithelioid leiomyoma in the seminal vesicle. This disease should be included in the differential diagnostic list of seminal vesicle tumors with epithelioid morphology.

Revealing topology with transformation optics.

Symmetry deepens our insight into a physical system and its interplay with topology enables the discovery of topological phases. Symmetry analysis is conventionally performed either in the physical space of interest, or in the corresponding reciprocal space. Here we borrow the concept of virtual space from transformation optics to demonstrate how a certain class of symmetries can be visualised in a transformed, spectrally related coordinate space, illuminating the underlying topological transitions. By projecting a plasmonic system in a higher-dimensional virtual space onto a lower-dimensional system in real space, we show how transformation optics allows us to construct a topologically non-trivial system by inspecting its modes in the virtual space. Interestingly, we find that the topological invariant can be controlled via the singularities in the conformal mapping, enabling the intuitive engineering of edge states. The confluence of transformation optics and topology here can be generalized to other wave realms beyond photonics.

Key Candidate Genes - VSIG2 of Colon Cancer Identified by Weighted Gene Co-Expression Network Analysis.

BACKGROUND: Colon adenocarcinoma (COAD) is one of the most common malignancies. To identify candidate genes that may be involved in colon adenocarcinoma development and progression, weighted gene co-expression network analysis (WGCNA) was used to construct gene co-expression networks to explore associations between gene sets and clinical features and to identify candidate biomarkers. Moreover, we intend to make a preliminary exploration on it. METHODS: Gene expression profiles and clinical information were collected from The Cancer Genome Atlas COAD database for analysis. The gene expression profiles of GSE106582 and GSE110224 were screened from the Gene Expression Omnibus database for verification. WGCNA analysis, functional pathway enrichment analysis, and prognosis analysis were performed on three databases. Target genes were selected from the key genes for experimental verification and research. RESULTS: Key genes obtained by WGCNA analysis were mainly enriched in key functions and pathways such as drug metabolism, steroid hormones, and retinol metabolism. A total of four prognostic genes were screened out: SELENBP1, NAT2, VSIG2, and CES2. VSIG2 was selected as the target gene for experimental verification, and its encoded protein was found to be mainly expressed in immune cells. Its expression was positively correlated with immune infiltration. CONCLUSIONS: VSIG2 was shown to be associated with immune invasion and antigen presentation in COAD, suggesting it plays an important role in COAD development and progression. It could be used as a potential biomarker or therapeutic target for COAD.

F-Type ATP Synthase Assembly Factors Atp11 and Atp12 in Arabidopsis.

Atp11p and Atp12p are members of two chaperone families essential for assembly of the mitochondrial ATP synthase in Saccharomyces cerevisiae and Homo sapiens. However, the role of their homologs in higher plants is unclear with regard to the assembly of both chloroplast ATP synthase (cpATPase) and mitochondrial ATP synthase (mtATPase). Here, we show that loss of either Atp11 or Atp12 is lethal in Arabidopsis. While Atp12 is only localized in mitochondria, Atp11 is present both in chloroplasts and mitochondria. Yeast two-hybrid analyses showed that, as their homologs in yeast, Atp11 specifically interacts with the ß subunit of the mtATPase and cpATPase, and Atp12 interacts with the α subunit of the mtATPase, implying that Atp11 and Atp12 fulfill a conserved task during assembly of ATP synthase. However, the binding sites for Atp11 in the ß subunit of mtATPase and cpATPase are slightly different, suggesting that the mechanisms of action may have evolved in different ways. Although Atp11 interacts with cpATPase ß subunit as the two assembly factors BFA3 and BFA1, they bind to different sites of the ß subunit. These results indicate that Atp11 is involved in the assembly of both cpATPase and mtATPase but Atp12 is specifically required for the assembly of mtATPase in higher plants.

In vivo antioxidant, hypoglycemic, and anti-tumor activities of anthocyanin extracts from purple sweet potato.

Anthocyanin from purple sweet potato (PSP) extracted by microwave baking (MB) and acidified electrolyzed water (AEW) exhibited antioxidant activity. After further purification by macroporous AB-8 resin, the color value of PSP anthocyanin (PSPA) reached 30.15 with a total flavonoid concentration of 932.5 mg/g. The purified extracts had more potent antioxidant activities than the crude extracts. After continuously administering the PSP extracts to 12-mo-old mice for 1 mo, the anti-aging index of the experimental group was not significantly different from that of 5-mo-old mice. To a certain degree, PSPA was also effective for controlling plasma glucose levels in male Streptozocin (STZ)-treated diabetic mice. In addition, the extracts inhibited Sarcoma S180 cell growth in ICR mice. Mice consuming the PSP extracts formed significantly fewer and smaller sarcomas than mice consuming the control diets. The highest inhibition rate was 69.03%. These results suggest that anthocyanin extracts from PSP not only exert strong antioxidant effects in vitro, but also had anti-aging, anti-hyperglycemic, and anti-tumor activities.