A mutant GH3 family ß-glucosidase from Oenococcus oeni exhibits superior adaptation to wine stresses and potential for improving wine aroma and phenolic profiles.

In this study, we conducted a comprehensive investigation into a GH3 family ß-glucosidase (BGL) from the wild-type strain of Oenococcus oeni and its mutated counterpart from the acid-tolerant mutant strain. Our analysis revealed the mutant BGL's remarkable capacity to adapt to wine-related stress conditions, including heightened tolerance to low pH, elevated ethanol concentrations, and metal ions. Additionally, the mutant BGL exhibited superior hydrolytic activity towards various substrates. Through de novo modeling, we identified specific amino acid mutations responsible for its resilience to low pH and high ethanol environments. In simulated wine conditions, the mutant BGL outperformed both wild-type and commercial BGLs, efficiently releasing terpene and phenolic aglycones from glycosides in wine grapes. These findings not only expand our understanding of O. oeni BGLs but also highlight their potential in enhancing wine production. The mutant BGL's enhanced adaptation to wine stress conditions opens promising avenue for improving wine quality and flavor.

Using foliar nitrogen application during veraison to improve the flavor components of grape and wine.

Nitrogen is involved in the winemaking process from grapevine growth to wine fermentation, and its precise utilization in vineyards can regulate grape and wine quality. Foliar nitrogen application during veraison (FNAV) could prevent nitrogen deficiency in grape and must in nitrogen-deficient vineyards. Moreover, FNAV also could improve certain flavor components of grape and wine, but little attention has been paid to FNAV. Therefore, this paper mainly reviews the difficulties encountered in current applications of nitrogen in vineyards and wineries, and the advantages of FNAV over the addition of nitrogen in soil and wineries. And it discusses that FNAV can increase yeast-assimilable nitrogen and phenolics, and scarcely affect volatile components of grape (must and wine), and points out the existing problems including the core issue and then puts forward future research directions. This information may indicate future directions for research, and provide a reference for viticulturists and winemakers on the precise application of nitrogen on grapevine and must to further improve grape and wine quality in nitrogen-deficient vineyards. © 2020 Society of Chemical Industry.

Endovenous radiofrequency ablation vs laser ablation in patients with lower extremity varicose veins: A meta-analysis.

BACKGROUND: Endovenous radiofrequency ablation (RFA) and laser ablation (LA) have been commonly used for treating lower extremity varicose veins (LEVVs). Their therapeutic effects have been widely recognized compared with conventional surgery. However, there have been some controversies regarding the choice between RFA and LA. The objective of our study was to conduct a systematic review and meta-analysis comparing the early and long-term outcomes of RFA and LA. METHODS: A comprehensive search was performed in the PubMed, Embase, and Cochrane databases to identify relevant literature on endovenous thermal ablation for primary LEVV up until June 2023. Randomized controlled trials, cohort studies, and case-control studies involving RFA and LA for LEVV treatment were included. The primary endpoints were the occlusion rate of the great saphenous vein (GSV) and occurrence of venous thrombotic events. Secondary outcomes included nerve injury, hyperpigmentation, burns, recurrence of VVs, postoperative pain, and phlebitis. Data were analyzed using Review Manager 5.3 software. RESULTS: A total of 29 studies met the inclusion criteria, consisting of 16 randomized controlled trials and 13 cohort studies. At 1 month, the occlusion rates of GSV were 98.35% for RFA and 98.04% for LA, whereas at 1 year, the rates were 93.13% for RFA and 94.18% for LA. Subgroup analyses revealed that RFA had higher GSV occlusion rates at 1 year since 2016 (93.27% vs 91.24%; odds ratio [OR], 1.35; 95% confidence interval [CI], 1.0-1.83; P = .05). The incidence of postoperative venous thrombotic events was 0.78% for RFA and 0.87% for LA at 1 month (OR, 1.46; 95% CI, 0.77-2.74; P = .24). RFA showed a reduced risk of burns and ecchymosis (OR, 0.65; 95% CI, 0.48-0.87; P = .005), postprocedural pain (mean difference, -0.85; 95% CI, -1.06 to -0.64; P < .001), recurrence of VVs (OR, 0.58; 95% CI, 0.36-0.92; P = .02), and paresthesia since 2016 (OR, 0.42; 95% CI, 0.19-0.91; P = .03), but an increased risk of skin pigmentation (OR, 1.75; 95% CI, 1.06-2.9; P = .03) compared with LA therapy. The rate of phlebitis was similar between RFA and LA (OR, 0.87; 95% CI, 0.33-2.27; P = .78). CONCLUSIONS: RFA and LA demonstrated similar efficacy in terms of early and long-term occlusion rates of GSV and the incidence of thrombotic and phlebitis complications. However, since 2016, RFA has shown higher GSV occlusion rates compared with LA. Furthermore, RFA was associated with fewer complications such as paresthesia, burns and ecchymosis, and recurrence of VVs when compared with LA.

Effects of ultraviolet and infrared radiation absence or presence on the aroma volatile compounds in winegrape during veraison.

Light environmental factors have been identified to influence grape aromas greatly. Among them, the effect of non-visible light on grape aroma compounds has scarcely been investigated during grape growth and development. In the present study, ultraviolet (UV) or infrared (IR) radiation was eliminated in the grape bunch zone, and the grape bunches were irradiated with UV or IR light in vitro. The effect of UV and IR radiation on the grape aroma profile of the Cabernet Sauvignon variety was assessed by headspace solid phase microextraction gas chromatography mass spectrometer (HS-SPME GC-MS). A total of 16 aroma compounds were identified in the grape berries under UV radiation absence (UV-) or IR radiation absence (IR-). They were classified into aliphatic alcohols, aliphatic acids, benzenolds, aldehydes, and monoterpenes. A total of 23 aroma compounds were identified in the grape berries under UV radiation presence (UV+) or IR radiation presence (IR+), which were classified into aliphatic alcohols, aliphatic ketones, aliphatic esters, aliphatic acids, monoterpenes, aldehydes, volatile phenols, and other volatiles. Linalool and hexanal aroma compounds were the most responsive to UV- and UV+, according to OPLS-DA analysis. Hexanal was increased by UV- and decreased by UV+, thus was negatively correlated with UV radiation. Benzaldehyde and 2-decanone were also found as the main differing aroma compounds according to VIP scores in the IR- and IR+, respectively. The significant differences of aroma compounds in three UV and IR intensities were also observed by headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS). The content of acetic acid, 2-methylbutanal, and pentanal were reduced with the radiation intensity increase, and the content of 2-3-butanedione, butyl acetate, and 1-hexanol was enhanced, especially with UV radiation. This study improves our understanding of the non-visible light role in volatile aroma compound accumulation and further expands on the useful wavelength for plant growth and development. Our study provides a theoretical basis for non-visible light field management and indoor plant growth applications.

19q13.12 KRAB zinc-finger protein ZNF383 represses p53 signaling pathway by interacting with p53.

As one of the most important tumor suppressors, the activity of p53 is precisely regulated. However, the mechanism of p53 regulation is still being elucidated and new regulatory molecules for p53 have also been frequently identified. Our previous works revealed that two members of the KRAB zinc-finger protein (KZFP) family Apak and PISA, which are located on human 19q13.12, participated in the regulation of p53 signaling pathway. KZFPs genes are mainly amplified via tandem in situ duplication during evolution, which indicates that similar sequences and functions may be conserved in evolutionarily and physically close KZFPs. Here, we revealed that ZNF383, another member of the KZFPs mapped at 19q13.12, could inhibit p53-mediated apoptosis and the activation of IFN-ß pathway by decreasing the H3K36me2 level at p53's binding sites and the attenuating the binding of p53 to its target genes. We further explored the effect of other KZFPs clustered on 19q13.12 on p53, and found that 85% of these KZFPs exerted p53-repressive activity. Intriguingly, an acidic amino acid-enriched sequence, the SAcL motif in the zinc-finger domains of these KZFPs, was found to be critical for p53 binding. Taken together, our findings revealed the KZFPs cluster located at 19q13.12 not only was involved in p53 regulation but also exhibited different features in the selective regulation of p53 and functional mechanisms, and for the first time, confirmed a motif in KZFPs that mediates the interaction of KZFPs and p53. These results would enrich the knowledge on the role, sequence features, and functional mechanisms of the KZFP family in p53 regulation.

ZNF498 promotes hepatocellular carcinogenesis by suppressing p53-mediated apoptosis and ferroptosis via the attenuation of p53 Ser46 phosphorylation.

BACKGROUND: Dysfunctional p53 signaling is one of the major causes of hepatocellular carcinoma (HCC) tumorigenesis and development, but the mechanisms underlying p53 inactivation in HCC have not been fully clarified. The role of Krüppel-associated box (KRAB)-type zinc-finger protein ZNF498 in tumorigenesis and the underlying mechanisms are poorly understood. METHODS: Clinical HCC samples were used to assess the association of ZNF498 expression with clinicopathological characteristics and patient outcomes. A mouse model in which HCC was induced by diethylnitrosamine (DEN) was used to explore the role of ZNF498 in HCC initiation and progression. ZNF498 overexpression and knockdown HCC cell lines were employed to examine the effects of ZNF498 on cellular proliferation, apoptosis, ferroptosis and tumor growth. Western blotting, immunoprecipitation, qPCR, luciferase assays and flow cytometry were also conducted to determine the underlying mechanisms related to ZNF498 function. RESULTS: ZNF498 was found to be highly expressed in HCC, and increased ZNF498 expression was positively correlated with advanced pathological grade and poor survival in HCC patients. Furthermore, ZNF498 promoted DEN-induced hepatocarcinogenesis and progression in mice. Mechanistically, ZNF498 directly interacted with p53 and suppressed p53 transcriptional activation by inhibiting p53 Ser46 phosphorylation. ZNF498 competed with p53INP1 for p53 binding and suppressed PKCδ- and p53INP1-mediated p53 Ser46 phosphorylation. In addition, functional assays revealed that ZNF498 promoted liver cancer cell growth in vivo and in vitro in a p53-dependent manner. Moreover, ZNF498 inhibited p53-mediated apoptosis and ferroptosis by attenuating p53 Ser46 phosphorylation. CONCLUSIONS: Our results strongly suggest that ZNF498 suppresses apoptosis and ferroptosis by attenuating p53 Ser46 phosphorylation in hepatocellular carcinogenesis, revealing a novel ZNF498-PKCδ-p53INP1-p53 axis in HCC cells that would enrich the non-mutation p53-inactivating mechanisms in HCC.

A hybrid quantum-classical neural network with deep residual learning.

Inspired by the success of classical neural networks, there has been tremendous effort to develop classical effective neural networks into quantum concept. In this paper, a novel hybrid quantum-classical neural network with deep residual learning (Res-HQCNN) is proposed. We firstly analyse how to connect residual block structure with a quantum neural network, and give the corresponding training algorithm. At the same time, the advantages and disadvantages of transforming deep residual learning into quantum concept are provided. As a result, the model can be trained in an end-to-end fashion, analogue to the backpropagation in classical neural networks. To explore the effectiveness of Res-HQCNN , we perform extensive experiments for quantum data with or without noisy on classical computer. The experimental results show the Res-HQCNN performs better to learn an unknown unitary transformation and has stronger robustness for noisy data, when compared to state of the arts. Moreover, the possible methods of combining residual learning with quantum neural networks are also discussed.

Foliar Phenylalanine Application Promoted Antioxidant Activities in Cabernet Sauvignon by Regulating Phenolic Biosynthesis.

The effects of foliar phenylalanine application during veraison (FPV) on phenolic biosynthesis and correlation between phenolic compositions and antioxidant activities in Cabernet Sauvignon grown in field and greenhouse were investigated. Solutions with 69 and 138 mg N/vine phenylalanine (Pe1 and Pe2, respectively) and an aqueous solution without nitrogen (CK) were sprayed three times during veraison. FPV significantly improved antioxidant activities in grapes using the two culture methods. The most contributory phenolic compositions to antioxidant activities were anthocyanins and stilbenes following FPV compared with CK. Phenylalanine metabolism, abscisic acid content, and expression levels of VvPAL, VvCHS, VvF3H, VvUFGT, and VvSTS in the phenolic synthesis pathway were increased from the first FPV to harvest. Although Pe2 significantly increased total phenolic contents than Pe1, antioxidant parameters were not markedly affected by the phenylalanine dose. Our finding revealed that FPV was a useful fertilization method to enhance antioxidant activities in grapes in nitrogen-deficient vineyards.

Biomass estimation and physicochemical characterization of winter vine prunings in the Chinese and global grape and wine industries.

The residual biomass of winter vine prunings (WVPs) in the Chinese and global grape and wine industries was investigated and estimated, and the physicochemical characteristics of Chinese WVPs were analyzed. The eight regions investigated within China showed a total annual regional WVP yield of 201-842 kt FW, with R1 and R6 region showing the highest and the lowest region yields, respectively. The R4 and R2 regions showed the highest and the lowest yield per tree. Table grapes showed considerably higher WVP yields than wine grapes, whereas the pergola systems showed considerably higher WVP yields than the hedge systems. In addition, older vines showed higher WVP yields than younger vines. Overall, the average WVP yield in China was 2.35 kg/tree FW with a range of 1.33-3.21 kg/tree FW. Globally, the estimated WVP yield has decreased gradually from 2000 to 2017 to 42.31 million ton FW; in contrast, estimated WVP yield in China has increased substantially over the same period to 6.04 million ton FW. Winter vine pruning was the leading source of solid grape waste in the grape and wine industry, both absolutely and proportionally, and was characterized by such properties as a high dry matter content, mild acidity, high levels of organic matter and nutrients, and low fat. It is clear that WVP represents a resource of immense value for generating additional wealth in China and in the global grape and wine industry.

Foliar nitrogen application from veraison to preharvest improved flavonoids, fatty acids and aliphatic volatiles composition in grapes and wines.

This study investigated the effects of foliar nitrogen application from veraison to preharvest (FNVH) on flavonoids, fatty acids and aliphatic volatiles in Cabernet Sauvignon grapes and wines. Solutions with 69 and 138 mg N/plant phenylalanine (P1 and P2, respectively), 69 and 138 mg N/plant urea (U1 and U2, respectively), as well as an aqueous solution without nitrogen (CK), were sprayed three times from veraison to preharvest. U1, P1 had the highest anthocyanins and acylated anthocyanins contents in grapes, respectively. U1 and P2 showed great potential to promote the accumulation of flavonols and flavanols in grapes and wines. U2 increased the contents of almost all free aliphatic volatiles in grapes, while it didn't affect the undesirable smell, and increased the concentrations of fruity esters in wines instead. The study showed FNVH was a useful fertilization way for improving contents of flavonoids and fruity aroma in grapes and wines in deficit-nitrogen vineyards.

Transcriptomic Analysis of Oenococcus oeni SD-2a Response to Acid Shock by RNA-Seq.

Oenococcus oeni can be applied to conduct malolactic fermentation (MLF), but also is the main species growing naturally in wine. Due to the high stress tolerance, it is an interesting model for investigating acid response mechanisms. In this study, the changes in the transcriptome of O.oeni SD-2a during the adaptation period have been studied. RNA-seq was introduced for the transcriptomic analysis of O. oeni samples treated with pH 4.8 and pH 3.0 at 0 and 1 h, respectively. Gene ontology (GO) and Kyoto encyclopedia of genes and genome (KEGG) were performed to compare the transcriptome data between different treatments. From GO analysis, the majority of differentially expressed genes (DEGs) (pH 3.0_1 h-VS-pH 4.8_1 h, pH 3.0_1 h-VS-pH 4.8_0 h, and pH 4.8_1 h-VS-pH 4.8_0 h) were found to be involved in the metabolic process, catalytic activity, cellular process, and binding. KEGG analysis reveals that the most functional gene categories affected by acid are membrane transport, amino acid metabolism and carbohydrate metabolism. Some genes, like the heat shock protein Hsp20, malate transporter and malate permease, were also over-expressed in response to acid stress. In addition, a considerable proportion of gene indicate a significantly different expression in this study, are novel, which needs to be investigated further. These results provide a new viewpoint and crucial resource on the acid stress response in O. oeni.