Vicinity Vision Transformer.

Vision transformers have shown great success on numerous computer vision tasks. However, their central component, softmax attention, prohibits vision transformers from scaling up to high-resolution images, due to both the computational complexity and memory footprint being quadratic. Linear attention was introduced in natural language processing (NLP) which reorders the self-attention mechanism to mitigate a similar issue, but directly applying existing linear attention to vision may not lead to satisfactory results. We investigate this problem and point out that existing linear attention methods ignore an inductive bias in vision tasks, i.e., 2D locality. In this article, we propose Vicinity Attention, which is a type of linear attention that integrates 2D locality. Specifically, for each image patch, we adjust its attention weight based on its 2D Manhattan distance from its neighbouring patches. In this case, we achieve 2D locality in a linear complexity where the neighbouring image patches receive stronger attention than far away patches. In addition, we propose a novel Vicinity Attention Block that is comprised of Feature Reduction Attention (FRA) and Feature Preserving Connection (FPC) in order to address the computational bottleneck of linear attention approaches, including our Vicinity Attention, whose complexity grows quadratically with respect to the feature dimension. The Vicinity Attention Block computes attention in a compressed feature space with an extra skip connection to retrieve the original feature distribution. We experimentally validate that the block further reduces computation without degenerating the accuracy. Finally, to validate the proposed methods, we build a linear vision transformer backbone named Vicinity Vision Transformer (VVT). Targeting general vision tasks, we build VVT in a pyramid structure with progressively reduced sequence length. We perform extensive experiments on CIFAR-100, ImageNet-1 k, and ADE20 K datasets to validate the effectiveness of our method. Our method has a slower growth rate in terms of computational overhead than previous transformer-based and convolution-based networks when the input resolution increases. In particular, our approach achieves state-of-the-art image classification accuracy with 50% fewer parameters than previous approaches.

Protamine 1 as a secreted colorectal cancer-specific antigen facilitating G1/S phase transition under nutrient stress conditions.

PURPOSE: Cancer testis antigens (CTAs) are optimal tumor diagnostic markers and involved in carcinogenesis. However, colorectal cancer (CRC) related CTAs are less reported with impressive diagnostic capability or relevance with tumor metabolism rewiring. Herein, we demonstrated CRC-related CTA, Protamine 1 (PRM1), as a promising diagnostic marker and involved in regulation of cellular growth under nutrient deficiency. METHODS: Transcriptomics of five paired CRC tissues was used to screen CRC-related CTAs. Capability of PRM1 to distinguish CRC was studied by detection of clinical samples through enzyme linked immunosorbent assay (ELISA). Cellular functions were investigated in CRC cell lines through in vivo and in vitro assays. RESULTS: By RNA-seq and detection in 824 clinical samples from two centers, PRM1 expression were upregulated in CRC tissues and patients` serum. Serum PRM1 showed impressive accuracy to diagnose CRC from healthy controls and benign gastrointestinal disease patients, particularly more sensitive for early-staged CRC. Furthermore, we reported that when cells were cultured in serum-reduced medium, PRM1 secretion was upregulated, and secreted PRM1 promoted CRC growth in culture and in mice. Additionally, G1/S phase transition of CRC cells was facilitated by PRM1 protein supplementation and overexpression via activation of PI3K/AKT/mTOR pathway in serum deficient medium. CONCLUSIONS: In general, our research presented PRM1 as a specific CRC antigen and illustrated the importance of PRM1 in CRC metabolism rewiring. The new vulnerability of CRC cells was also provided with the potential to be targeted in future. Diagnostic value and grow factor-like biofunction of PRM1 A represents the secretion process of PRM1 regulated by nutrient deficiency. B represents activation of PI3K/AKT/mTOR pathway of secreted PRM1.

Identification of Key Genes Related With Aspartic Acid Metabolism and Corresponding Protein Expression in Human Colon Cancer With Postoperative Prognosis and the Underlying Molecular Pathways Prediction.

Objective: Colon cancer is one of the most frequent and lethal neoplasias. Altered metabolic activity is a well-known hallmark for cancer. The present study is aiming to screen key genes associated with tumor metabolism and construct a prognostic signature of colon cancer patients. Methods: Glutamine- and UC- metabolism related genes were downloaded from GSEA MsigDB. Three key genes were screened by Cox regression analysis with data samples downloaded from TCGA and GSE29623 database. Consistent clustering based on the prognostic genes identified was employed to divide the colon cancer samples into two clusters with significant OS differences. The mRNA and protein expression of the key genes in colon tissues and matched adjacent noncancerous tissues of 16 patients were detected by IHC, qPCR, and Western blot to validate the constructed clustering model. GO, GSVA, and IPA were used to predict the relevant metabolic pathways. Results: According to the three key genes identified, i.e., ASNS, CEBPA, and CAD, the cohort can be divided into two clusters with prognosis differences. Clinical specimen results confirmed that the risk model established was effective, and the different expression pattern of ASNS and CEBPA was correlated with TNM stage and lymph node metastasis, whilst that of CAD was correlated with post-operative tumor metastasis and recurrence. Molecular mechanism prediction indicated that CREB, insulin, and RNA Pol II were the key nodes affecting CEBPA and ASNS expression. Moreover, TIDE algorithm reflected the better immune response of the cluster with shorter OS. Further immune infiltration and checkpoints analyses provided important reference for clinicians to perform individualized immunotherapy. Conclusion: Differential expression profile of three aspartic acid metabolic-associated genes, ASNS, CEBPA, and CAD, can be considered as a risk model with a good evaluation effect on the prognosis of colon cancer patients.

Role of glutamine and its metabolite ammonia in crosstalk of cancer-associated fibroblasts and cancer cells.

Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, play an indispensable role in cancer initiation, progression, metastasis, and metabolism. The limitations of traditional treatments can be partly attributed to the lack of understanding of the role of the tumor stroma. For this reason, CAF targeting is gradually gaining attention, and many studies are trying to overcome the limitations of tumor treatment with CAF as a breakthrough. Glutamine (GLN) has been called a "nitrogen reservoir" for cancer cells because of its role in supporting anabolic processes such as fuel proliferation and nucleotide synthesis, but ammonia is a byproduct of the metabolism of GLN and other nitrogenous compounds. Moreover, in some studies, GLN has been reported as a fundamental nitrogen source that can support tumor biomass. In this review, we discuss the latest findings on the role of GLN and ammonia in the crosstalk between CAFs and cancer cells as well as the potential therapeutic implications of nitrogen metabolism.

Effect of Potato Pulp Pectic Polysaccharide on the Stability of Acidified Milk Drinks.

In order to broaden the application of potato pulp pectic polysaccharide (PPP) in stabilizing acidified milk drinks (AMDs) and investigate the stabilizing effect and physical properties of AMDs prepared with PPP, a comparative study was made among PPP, commercial high methoxyl pectin (HMP) and low methoxyl pectin (LMP). The zeta potential, rheology, particle size and serum separation of AMDs were evaluated after preparing with PPP, HMP and LMP, respectively. Results indicated that PPP led to lower serum separation than LMP (14.65% for AMDs prepared with 0.5% PPP compared to 25.05% for AMDs prepared with 0.5% LMP), but still higher than HMP (9.09% for AMDs prepared with 0.5% HMP). However, narrower particle size distribution and lower viscosity of AMDs was achieved by PPP than by LMP and HMP. PPP can electrostatically adsorb on the surface of casein and its abundant neutral sugar side chains would provide steric hindrance to prevent casein flocculation in AMDs. Our results might provide some new ideas for the application of PPP in improving the stability of AMDs.

Lnc HAGLR Promotes Colon Cancer Progression Through Sponging miR-185-5p and Activating CDK4 and CDK6 in vitro and in vivo.

BACKGROUND/AIM: LncRNA plays a key role in tumor progression. HAGLR functions as an oncogene in many cancers. However, the molecular mechanism of HAGLR in colon cancer is still unclear. METHODS: qRT-PCR was used to measure the expression of HAGLR, miR-185-5p in colon cancer. The expression of CDK4 and CDK6 was detected by Western blot. CCK-8 assay, EdU staining, transwell and Annexin V-FITC/PI assay were used to analyze the effect of HAGLR and miR-185-5p on cell proliferation, invasion, migration and apoptosis. Bioinformatic analysis and luciferase were used to analyze the target genes of HAGLR and miR-185-5p. Nude mice were used to detect mouse tumor changes. RESULTS: Compared with normal colon cancer tissues and cells, the expression of HAGLR was increased in colon cancer tissues and cells. In addition, the expression of HAGLR down-regulation inhibited the growth, migration, and invasion of colon cancer cells. MiR-185-5p was reduced in colon cancer, and CDK4 and CDK6 acted as target genes of miR-185-5p to regulate the progress of colon cancer. And CDK4 and CDK6 were predicted as downstream targets of miR-185-5p. Finally, it was demonstrated that HAGLR regulated tumor progression in vivo. CONCLUSION: Lnc HAGLR promoted the development of colon cancer by miR-185-5p/CDK4/CDK6 axis, and lnc HAGLR might be potential target for colon cancer.

KRas-ERK signalling promotes the onset and maintenance of uveal melanoma through regulating JMJD6-mediated H2A.X phosphorylation at tyrosine 39.

Since DNA damage is a first incident occurred during a tumour attack, it is rational that histone H2A.X phosphorylation on tyrosine 39 (H2A.XY39ph) may act as a tumour-relevant factor. This study was aimed to test the authenticity of the hypothesis. Uveal melanoma MP65 cells were transfected for expression of KRas mutated. H2A.X phosphorylation and ERK1/2 was measured, and transwell experiment was performed to examine the consequents of H2A.XY39ph on MP65 cells developing and migration. Regulatory relationship between H2A.XY39ph and ERK1/2 downstream genes were measured. Moreover, whether JMJD6 and MDM2 are involved in H2A.X phosphorylation was studied. Mutation of Ras activated ERK1/2 signalling and inhibited H2A.X phosphorylation at Y39. Silence of H2A.XY39ph contributed to the regulation of MP65 cells growth, migration and transcription of ERK1/2 downstream genes, including CYR61, IGFBP3, WNT16B, NT5E, GDF15 and CARD16. The repressed H2A.X phosphorylation through Ras-ERK1/2 signalling might be through MDM2-mediated JMJD6 degradation. Our study suggested that Ras-ERK1/2 signalling inhibited H2A.X phosphorylation at Y39, which led to the uncontrolled developing and migration of uveal melanoma cells. In addition, H2A.X phosphorylation was mediated possibly through JMJD6 which could be degraded by MDM2.

Controlled ultrasound treatments modify the morphology and physical properties of rice starch rather than the fine structure.

To further investigate how controlled ultrasound treatments affect the morphology, physical property and fine structure of rice starch granules, the starch suspended in water was treated with different ultrasonic power levels (150, 300, 450 and 600 W) at 25 °C for 20 min. XRD, FT-IR and Raman spectroscopy were performed to characterise the long-range and short-range ordered structure of starch granules. Results indicated that ultrasound slightly destroyed the amorphous region of starch granules, while the A-type crystalline pattern remained unchanged. The result of chain length distributions showed that the fine structure of rice starch was not significantly changed by ultrasound treatment. SEM and particle size distribution demonstrated that ultrasound induced fissures and pores on the granule surface and elevated the homogeneity of granules, with minimum effect on the granule size. In addition, the thermal and pasting properties of rice starch were also measured by DSC and RVA. Results showed that after ultrasound treatments, the peak and breakdown viscosity increased, while the peak time, pasting temperature and gelatinisation enthalpy decreased. Overall, controlled ultrasound treatments dominantly modified the morphology and physical property of rice starch rather than the fine structure, providing additional information for the application of ultrasound on starch modification.

Retracted: Ras-PI3K-AKT signaling promotes the occurrence and development of uveal melanoma by downregulating H3K56ac expression.

BACKGROUND: Uveal melanoma (UM) is an intraocular malignant tumor characterized by rapid progression and recurrence. The current conventional treatments are unsatisfactory. Histone acetylation at H3 lysine 56 (H3K56ac) has been reported to be a tumor suppressor in breast cancer. However, whether H3K56ac prevents the occurrence and development of UM remains uninvestigated. The study aimed to explore the regulatory effect of H3K56ac on Ras-PI3K-AKT induced UM cells proliferation and migration. METHODS: The vectors of pEGFP-RasWT , pEGFP-K-Ras G12V/Y40C , and pEGFP-N1 were transfected into MP46 cells, and protein levels of phosphorylated AKT Ser473 and H3K56ac were examined using western blot analysis. The effect of H3K56ac on cell proliferation and migration were studied using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide, colony formation, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and chromatin immunoprecipitation assays were performed to determine the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) downstream genes. Further, the regulatory effects of silent mating type information regulation 2 homolog-1 (SIRT1), general control nonderepressible 5 (GCN5), and mouse double minute 2 homolog (MDM2) on Ras-PI3K-AKT affected H3K56ac expression were also investigated. RESULTS: H3K56ac expression was specifically downregulated by Ras-PI3K-AKT activation pathway. H3K56ac inhibited the tumorigenic effect of Ras-PI3K-AKT on MP46 cells viability, colony formation, and migration, as well as participated in regulating the transcription of PI3K/AKT downstream genes. SIRT1 silence recovered H3K56ac expression, and reversed the tumorigenic effect of Ras-PI3K-AKT activation on MP46 cells. Downregulation of H3K56ac induced by Ras-PI3K-AKT activation was found to be associated with MDM2-mediated the degradation of GCN5. CONCLUSIONS: The results demonstrated that Ras-PI3K-AKT signaling promoted UM cells proliferation and migration via downregulation of H3K56ac expression, which might be related to MDM2-mediated the degradation of GCN5.

Retracted: Ras-ERK1/2 signaling promotes the development of uveal melanoma by downregulating H3K14ac.

Ras-extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) signaling has been proposed as the crucial regulators in the development of various cancers. Histone acetylation at H3 lysine 14 (H3K14ac) is closely associated with gene expression and DNA damage. However, whether H3K14ac participates in mediating Ras-ERK1/2-induced cell proliferation and migration in uveal melanoma cells remains unknown. The purpose of this study is to investigate the effect of H3K14ac on Ras-ERK1/2 affected uveal melanoma cell phenotypes. MP65 cells were transfected with Ras WT and Ras G12V/T35S , the unloaded plasmid of pEGFP-N1 served as a negative control. Protein levels of phosphorylated ERK1/2 Thr202 and H3K14ac were assessed by western blot assay. Cell viability, number of colonies, migration, and the downstream genes of ERK1/2 were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2-H-tetrazolium bromide, soft-agar colony formation, transwell, and chromatin immunoprecipitation assays. HA-tag vectors of CLR3 and TIP60 and the small interfering RNAs that specific for CLR3 and MDM2 were transfected into MP65 cells to uncover the effects of CLR3, TIP60, and MDM2 on Ras-ERK1/2 mediated H3K14ac expression and MP65 cell phenotypes. We found that, Ras-ERK1/2 decreased H3K14ac expression in MP65 cells, and H3K14ac significantly suppressed Ras-ERK1/2-induced cell viability, colony formation, and migration in MP65 cells. Moreover, the transcription of CYR61, IGFBP3, WNT16B, NT5E, GDF15, and CARD16 was regulated by H3K14ac. Additionally, CLR3 silence recovered H3K14ac expression and reversed the effect of Ras-ERK1/2 on MP65 cell proliferation, migration and the mRNAs of ERK1/2 downstream genes. Besides, Ras-ERK1/2 decreased H3K14ac expression by MDM2-mediated TIP60 degradation. In conclusion, Ras-ERK1/2 promoted uveal melanoma cells growth and migration by downregulating H3K14ac via MDM2-mediated TIP60 degradation.

Curcumin inhibits proliferation, migration, invasion and promotes apoptosis of retinoblastoma cell lines through modulation of miR-99a and JAK/STAT pathway.

BACKGROUND: Curcumin, a primary active ingredient extracted from the Curcuma longa, has been recently identified as a potential anti-tumor agent in multiple kinds of cancers. However, the effect of curcumin on retinoblastoma (Rb) is still unclear. Therefore, we attempted to reveal the functional impacts and the underlying mechanisms of curcumin in Rb cells. METHODS: Two Rb cell lines SO-Rb50 and Y79 were pre-treated with various doses of curcumin, and then cell proliferation, apoptosis, migration, and invasion were assessed, respectively. Further, regulatory effects of curcumin on miR-99a expression, as well as the activation of JAK/STAT pathway were studied. RESULTS: Data showed that curcumin significantly inhibited the viability, colony formation capacity, migration and invasion, while induced apoptosis of SO-Rb50 and Y79 cells. Up-regulation of miR-99a was observed in curcumin-treated cells. Curcumin suppressed the phosphorylation levels of JAK1, STAT1, and STAT3, while curcumin did not inhibit the activation of JAK/STAT pathway when miR-99a was knocked down. CONCLUSION: Curcumin inhibited proliferation, migration, invasion, but promoted apoptosis of Rb cells. The anti-tumor activities of curcumin on Rb cells appeared to be via up-regulation of miR-99a, and thereby inhibition of JAK/STAT pathway.

Autophagy Inhibitor (LY294002) and 5-fluorouracil (5-FU) Combination-Based Nanoliposome for Enhanced Efficacy Against Esophageal Squamous Cell Carcinoma.

In this study, 5-fluorouracil (5-FU) and LY294002 (LY)-loaded PEGylated nanoliposome was prepared to target esophageal squamous cell carcinoma (ESCC). The particles were characterized in terms of physicochemical and biological parameters. The co-delivery of autophagy inhibitor and chemotherapeutic drug in a single carrier was successfully accomplished. The two components from 5-FU and LY-loaded PEGylated nanoliposome (FLNP) released in a controlled manner with LY relatively released faster compared to that of 5-FU. FLNP showed a receptor-mediated cellular uptake that will allow the gradual release of drug in the acidic environment. The cellular uptake of nanoparticles (NP) was further confirmed by FACS analysis. The combination of 5-FU and LY resulted in higher cytotoxic effect compared to that of individual drugs. Most importantly, FLNP exhibited a significantly higher anticancer effect in cancer cells compared to that of free cocktail combinations. The faster release of LY from FLNP leads to autophagy inhibition that improves the sensitivity of cancer cells towards 5-FU, resulting in more cell death. Consistently, FLNP induced a greater apoptosis (~ 48%) of cancer cells compared to that of any other groups. Western blot analysis clearly showed that 5-FU and LY individually increased the expression of caspase-3 and PARP, while as expected FLNP induced a remarkable expression of these protein markers indicating the superior anticancer effect. We believe that the programmed release of autophagy inhibitor and chemotherapeutic drug from a single nanocarrier will increase the prospect of anticancer therapy in ESCC.

Aroma modulation of Cabernet Gernischt dry red wine by optimal enzyme treatment strategy in winemaking.

Cabernet Gernischt (CG) is a famous Chinese wine grape cultivar, the red wine of which is known for its green trait, especially when produced from grapes cultivated in regions with monsoon climate. To modify CG wine aroma, three enzyme preparations (H. uvarum extracellular enzyme, AR2000, and pectinase) were introduced in different winemaking stages with Saccharomyces cerevisiae. Free and bound aroma compounds in young wines were detected using headspace solid-phase micro-extraction and gas chromatography-mass spectrometry, and aroma characteristics were quantified by trained panelists. Results showed that simultaneous inoculation of enzymes and yeasts improved wine aroma. Partial least-squares regression revealed that the green trait was due mainly to varietal compounds, especially C6 compounds, and could be partly weakened by fermentative compounds. Moreover, H. uvarum enzyme treatments enriched the acid fruit note of CG wine by enhancing the synergistic effect of varietal volatiles and certain fermentative compounds, such as esters and phenylethyls.

Evaluation of aroma enhancement for "Ecolly" dry white wines by mixed inoculation of selected Rhodotorula mucilaginosa and Saccharomyces cerevisiae.

To improve the aroma profile of Ecolly dry white wine, the simultaneous and sequential inoculations of selected Rhodotorula mucilaginosa and Saccharomyces cerevisiae were performed in wine making of this work. The two yeasts were mixed in various ratios for making the mixed inoculum. The amount of volatiles and aroma characteristics were determined the following year. Mixed fermentation improved both the varietal and fermentative aroma compound composition, especially that of (Z)-3-hexene-1-ol, nerol oxide, certain acetates and ethyls group compounds. Citrus, sweet fruit, acid fruit, berry, and floral aroma traits were enhanced by mixed fermentation; however, an animal note was introduced upon using higher amounts of R. mucilaginosa. Aroma traits were regressed with volatiles as observed by the partial least-square regression method. Analysis of correlation coefficients revealed that the aroma traits were the multiple interactions of volatile compounds, with the fermentative volatiles having more impact on aroma than varietal compounds.

Poly[hexa-aqua-(µ9-cyclo-hexane-1,2,3,4,5,6-hexa-carboxyl-ato)trimanganese(II)].

The asymmetric unit of the title compound, [Mn3(C12H6O12)(H2O)6] n , comprises one Mn(II) ion, one third of a cyclo-hexane-1,2,3,4,5,6-hexa-carboxyl-ate anion and two aqua ligands. The anion is completed by application of a -3 axis. The Mn(II) ion is six-coordinated by six O atoms from two aqua ligands and three different cyclo-hexa-carboxyl-ate anions in an octa-hedral geometry. The six carboxyl-ate groups adopt a bridging bidentate mode to ligate the Mn(II) ions. Thus, each cyclo-hexane-1,2,3,4,5,6-hexa-carboxyl-ate anion adopts a µ9-connected mode, ligating nine different Mn(II) ions and forming a three-dimensional framework. In the framework, there are strong O-H⋯O hydrogen-bonding inter-actions, which further stabilize the crystal structure.

Tetra-aqua-bis-[4-(4H-1,2,4-triazol-4-yl)benzoato-κN]nickel(II) deca-hydrate.

In the title compound, [Ni(C(9)H(6)N(3)O(2))(2)(H(2)O)(4)]·10H(2)O, the Ni(II) ion lies on a twofold rotation axis and displays a slightly distorted octa-hedral geometry defined by two N atoms from two monodentate 4-(1,2,4-triazol-4-yl)benzoate ligands and four water mol-ecules, two of which also lie on the twofold rotation axis. In the crystal, the complex mol-ecules and uncoordinated water mol-ecules are linked via inter-molecular O-H⋯N and O-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular network. π-π inter-actions between the benzene rings provide additional stability of the crystal packing [centroid-centroid distance = 3.792 (2) Å].