Deterministic distribution of multipartite entanglement in a quantum network by continuous-variable polarization states.

Quantum network plays a vitally important role in the practical application of quantum information, which requires the deterministic entanglement distribution among multiple remote users. Here, we propose a feasible scheme to deterministically distribute quadripartite entanglement by continuous-variable (CV) polarization states. The quantum server prepares the quadripartite CV polarization entanglement and distributes them to four remote users via optical fiber. In this way, the measurement of CV polarization entanglement is local oscillation free, which makes the long distance entanglement distribution in commercial optical fiber communication networks possible. Furthermore, both the Greenberger-Horne-Zeilinger-like (GHZ-like) and cluster-like polarization entangled states can be distributed among four users by controlling the beam splitter network in quantum server, which are confirmed by the extended criteria for polarization entanglement of multipartite optical modes. The protocol provides the direct reference for experimental implementation and can be directly extended to quantum network with more users, which is essential for a metropolitan quantum network.

Stabilization improvement of the squeezed optical fields using a high signal-to-noise ratio bootstrap photodetector.

High-precision cavity locking is crucial for squeezing optical fields. Here, a bootstrapped low-noise photodetector is utilized in the generation process of the squeezed state of light. This process is based on a combination of a modified trans-impedance amplifier (TIA) circuit and a two-stage bootstrap amplifier circuit. This not only achieves high-precision and long-term stable locking of the optical cavity, but it also improves the degree to which the light field is squeezed. The experiment results show that the detector has a high signal-to-noise ratio (SNR) of 26.7 dB at the analysis frequency of 3 MHz when measuring the shot noise with an injection optical power of 800 µW, and the equivalent optical power noise level is lower than 2.4 pW/Hz in the frequency range of 1-30 MHz. Moreover, the squeezing degree of the quadrature amplitude squeezed state light field can be improved by more than 34.9% when the detector is used for optical cavity locking. The photodetector is useful in continuous variable (CV) quantum information research.

Enhancing regioselectivity of sucrose phosphorylase by loop engineering for glycosylation of L-ascorbic acid.

Sucrose phosphorylase (SPase) has a remarkable capacity to synthesize numerous glucosides from abundantly available sucrose under mild conditions but suffers from specificity and regioselectivity issues. In this study, a loop engineering strategy was introduced to enhance the regioselectivity and substrate specificity of SPase for the efficient synthesis of 2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G) via L-ascorbic acid (L-AA). P134, L341, and L343 were identified as "hotspots" for modulating the flexibility of loops, which significantly influenced the H-bonding network of L-AA in the active site, as well as the entrance of the substrate channel, thereby altering the regioselectivity and substrate specificity. Finally, the mutant L341V/L343F, with near-perfect control of the selectivity synthesis of the 2-OH group of L-AA (> 99%), was obtained. The AA-2G production by the mutant reached 244 g L-1 in a whole-cell biotransformation system, and the conversion rate of L-AA reached 64%, which is the highest level reported to date. Our work also provides a successful loop engineering case for modulating the regioselectivity and specificity of sucrose phosphorylase. KEY POINTS: • "Hotspots" were identified in the flexible loops of sucrose phosphorylase. • Mutants exhibited improved regioselectivity and specificity against L-ascorbic acid. • Synthesized AA-2G with high yield and regioselectivity by whole-cell of mutant.

The optimized biocatalytic synthesis of (S)-methyl 2-chlorobutanoate by Acinetobacter sp. lipase.

Epilepsy is a chronic disease caused by sudden abnormal discharge of brain neurons, leading to transient brain dysfunction. Levetiracetam, developed by the UCB company in Belgium, is an effective drug for the treatment of epilepsy. (S)-Methyl 2-chlorobutanoate is an important chiral building block of levetiracetam, which has attracted a great deal of attention. In this study, a strain of lipase-produced Acinetobacter sp. zjutfet-1 was screened from soil samples. At optimized conditions for fermentation and biocatalysis, the bacterial lipase exhibited high catalytic activity for hydrolysis and stereoselectivity toward racemic methyl 2-chlorobutanoate. When the enzymatic reaction was carried out in 6% of racemic substrate, the enantiomeric excess (e.e.s ) reached more than 95%, with a yield of over 86%. Therefore, this lipase can efficiently resolve racemic methyl 2-chlorobutanoate and obtain (S)-methyl 2-chlorobutanoate, which presents great potential in the industrial production of levetiracetam.

Batch-feeding whole-cell catalytic synthesis of α-arbutin by amylosucrase from Xanthomonas campestris.

α-Arbutin is an effective skin-whitening cosmetic ingredient and can be synthesized through hydroquinone glycosylation. In this study, amylosucrase (Amy-1) from Xanthomonas campestris pv. campestris 8004 was newly identified as a sucrose-utilizing glycosylating hydroquinone enzyme. Its kinetic parameters showed a seven-time higher affinity to hydroquinone than maltose-utilizing α-glycosidase. The glycosylation of HQ can be quickly achieved with over 99% conversion when a high molar ratio of glycoside donor to acceptor (80:1) was used. A batch-feeding catalysis method was designed to eliminate HQ inhibition with high productivity (> 36.4 mM h-1). Besides, to eliminate the serious inhibition caused by the accumulated hydroquinone oxidation products, the whole-cell catalysis was further proposed. 306 mM of α-arbutin was finally achieved with 95% molar conversion rate within 15 h. Hence, the batch-feeding whole-cell biocatalysis by Amy-1 is a promising technology for α-arbutin production with enhanced yield and molar conversion rate.

Quantum Secret Sharing Among Four Players Using Multipartite Bound Entanglement of an Optical Field.

Secret sharing is a conventional technique for realizing secure communications in information networks, where a dealer distributes to n players a secret, which can only be decoded through the cooperation of k (n/2

An intensive study on aerosol optical properties and affecting factors in Nanjing, China.

The optical properties of aerosol as well as their impacting factors were investigated at a suburb site in Nanjing during autumn from 14 to 28 November 2012. More severe pollution was found together with lower visibility. The average scattering and absorption coefficients (Bsca and Babs) were 375.7 ± 209.5 and 41.6 ± 18.7 Mm(-1), respectively. Higher Ångström absorption and scattering exponents were attributed to the presence of more aged aerosol with smaller particles. Relative humidity (RH) was a key factor affecting aerosol extinction. High RH resulted in the impairment of visibility, with hygroscopic growth being independent of the dry extinction coefficient. The hygroscopic growth factor was 1.8 ± 1.2 with RH from 19% to 85%. Light absorption was enhanced by organic carbon (OC), elemental carbon (EC) and EC coatings, with contributions of 26%, 44% and 75% (532 nm), respectively. The Bsca and Babs increased with increasing N100 (number concentration of PM2.5 with diameter above 100 nm), PM1 surface concentration and PM2.5 mass concentration with good correlation.

Activated phosphatidylinositol 3-kinase/Akt inhibits the transition of endothelial progenitor cells to mesenchymal cells by regulating the forkhead box subgroup O-3a signaling.

BACKGROUND AND AIMS: Endothelial progenitor cells (EPCs) differentiate into mature endothelial cells and may thus be candidates for ischemic disease therapy; however, the transition of EPCs to mesenchymal cells is not fully understood. We explored the role of phosphatidylinositol 3-kinase (PI3K)/Akt signaling in endothelial-to-mesenchymal transition (EndMT) induced by transforming growth factor beta 1 (TGF-ß1). METHODS: Rat bone marrow-derived EPCs were isolated by using Ficoll-Isopaque Plus density-gradient centrifugation. EndMT was induced by TGF-ß1 (5 ng/mL). PI3K/Akt signaling was activated by IGF-1 or Lenti-PIK3R2 shRNA. Additionally, FoxO3a expression was suppressed by a lentiviral vector (Lenti-FoxO3a shRNA). Smad3 and FoxO3a co-localization was detected by confocal immunofluorescence microscopy. The expressions of molecules involved in EndMT were exmined by using Western-blot analysis. RESULTS: EndMT of EPCs was fully developed after TGF-ß1 treatment (5 ng/mL) for 7 days. PIK3R2 expression in EPCs was driven by TGF-ß1. Lenti-PIK3R2 shRNA blocked alpha-smooth muscle actin (α-SMA) expression in EPCs treated with TGF-ß1, drove PI3K/Akt activation, and increased expression of phosphorylated FoxO3a instead of phosphorylated Smad3. The effect of Lenti-PIK3R2 shRNA was reduced by LY294002, a specific inhibitor of PI3K. IGF-1 attenuated α-SMA protein expression in EPCs treated with TGF-ß1. Similar to Lenti-PIK3R2 shRNA, IGF-1 also inhibited and elevated the phosphorylation of Smad3 and FoxO3a, respectively. IGF-1 disrupted the co-localization of these proteins in EPCs treated with TGF-ß1. Lenti-FoxO3a shRNA transfection of EPCs suppressed expression of FoxO3a as well as that of the mesenchymal markers SM22α and α-SMA. CONCLUSIONS: Activation of PI3K/Akt signaling by Lenti-PIK3R2 shRNA or by exogenous IGF-1 inhibits EndMT in EPCs via negative regulation of FoxO3a-dependent signaling.

Curcumin Modulates Macrophage Polarization Through the Inhibition of the Toll-Like Receptor 4 Expression and its Signaling Pathways.

BACKGROUND: Curcumin, the active ingredient in curcuma rhizomes, has a wide range of therapeutic effects. However, its atheroprotective activity in human acute monocytic leukemia THP-1 cells remains unclear. We investigated the activity and molecular mechanism of action of curcumin in polarized macrophages. METHODS: Phorbol myristate acetate (PMA)-treated THP-1 cells were differentiated to macrophages, which were further polarized to M1 cells by lipopolysaccharide (LPS; 1 µg/ml) and interferon (IFN)-γ (20 ng/ml) and treated with varying curcumin concentrations. [3H]thymidine (3H-TdR) incorporation assays were utilized to measure curcumin-induced growth inhibition. The expression of tumor necrosis factor-α (TNF-α), interleukin (IL-6), and IL-12B (p40) were measured by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Macrophage polarization and its mechanism were evaluated by flow cytometry and western blot. Additionally, toll-like receptor 4 (TLR4) small interfering RNA and mitogen-activated protein kinase (MAPK) inhibitors were used to further confirm the molecular mechanism of curcumin on macrophage polarization. RESULTS: Curcumin dose-dependently inhibited M1 macrophage polarization and the production of TNF-α, IL-6, and IL-12B (p40). It also decreased TLR4 expression, which regulates M1 macrophage polarization. Furthermore, curcumin significantly inhibited the phosphorylation of ERK, JNK, p38, and nuclear factor (NF)-κB. In contrast, SiTLR4 in combination with p-JNK, p-ERK, and p-p38 inhibition reduced the effect of curcumin on polarization. CONCLUSIONS: Curcumin can modulate macrophage polarization through TLR4-mediated signaling pathway inhibition, indicating that its effect on macrophage polarization is related to its anti-inflammatory and atheroprotective effects. Our data suggest that curcumin could be used as a therapeutic agent in atherosclerosis.

Experimental generation of 8.4 dB entangled state with an optical cavity involving a wedged type-II nonlinear crystal.

Entangled state of light is one of the essential quantum resources in quantum information science and technology. Especially, when the fundamental principle experiments have been achieved in labs and the applications of continuous variable quantum information in the real world are considered, it is crucial to design and construct the generation devices of entangled states with high entanglement and compact configuration. We have designed and built an efficient and compact light source of entangled state, which is a non-degenerate optical parametric amplifier (NOPA) with the triple resonance of the pump and two subharmonic modes. A wedged type-II KTP crystal inside the NOPA is used for implementing frequency-down-conversion of the pump field to generate the optical entangled state and achieving the dispersion compensation between the pump and the subharmonic waves. The EPR entangled state of light with quantum correlations of 8.4 dB for both amplitude and phase quadratures are experimentally produced by a single NOPA under the pump power of 75 mW.

Antiphospholipid syndrome presenting as extensive skin ulcers on unilateral lower extremity: a case report.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent arterial and venous thrombosis, habitual fetal miscarriages, often accompanied by mild to moderate thrombocytopenia, and persistent moderate-to-high titer positivity for antiphospholipid antibodies (aPLs). However, patients with antiphospholipid antibodies may also present with several nonthrombotic clinical manifestations, such as thrombocytopenia, cardiac valve disease, nephropathy, skin ulcers, or cognitive dysfunction, which are collectively referred to as nonstandard manifestations of APS. Of these, for APS with predominantly cutaneous ulcers, previous reports have focused on APS with combined cutaneous vasculitis, and its medical treatment, rather than cutaneous ulcers with predominantly fatty inflammatory lesions, and the associated surgical treatment. Here, we admitted a relatively rare case of primary APS with extensive skin ulceration of the right lower extremity, without cutaneous vasculitis, in the presence of extensive and severe inflammatory lipoatrophy, carrying anti-ß2-glycoprotein I and lupus anticoagulant, which is reported as follows, with a view to raising awareness of this disease.

Schisandra chinensis Bee Pollen Ameliorates Colitis in Mice by Modulating Gut Microbiota and Regulating Treg/Th17 Balance.

Colitis is a chronic disease associated with alterations in the composition of gut microbiota. Schisandra chinensis bee pollen extract (SCPE) has been proved to be rich in phenolic compounds and effective in modulating gut microbiota, but its effect on colitis and the underlying mechanism remains unclear. This study investigates the relationship between colitis amelioration and the gut microbiota regulation of SCPE via fecal microbial transplantation (FMT). The results showed that administration of 20.4 g/kg BW of SCPE could primely ameliorate colitis induced by dextran sulfate sodium (DSS) in mice, showing as more integration of colon tissue structure and the colonic epithelial barrier, as well as lower oxidative stress and inflammation levels compared with colitis mice. Moreover, SCPE supplement restored the balance of T regulatory (Treg) cells and T helper 17 (Th17) cells. Gut microbiota analysis showed SCPE treatment could reshape the gut microbiota balance and improve the abundance of gut microbiota, especially the beneficial bacteria (Akkermansia and Lactobacillus) related to the production of short-chain fatty acids and the regulation of immunity. Most importantly, the protection of 20.4 g/kg BW of SCPE on colitis can be perfectly transmitted by fecal microbiota. Therefore, the gut microbiota-SCFAS-Treg/Th17 axis can be the main mechanism for SCPE to ameliorate colitis. This study suggests that SCPE can be a new promising functional food for prevention and treatment of colitis by reshaping gut microbiota and regulating gut immunity.

Association between trajectories in cardiac damage and clinical outcomes after transcatheter aortic valve replacement.

BACKGROUND: There is little evidence of evolution in cardiac damage after transcatheter aortic valve replacement (TAVR) in aortic stenosis (AS) patients. Less is known about the prognostic value and potential utility of different cardiac damage trajectories following TAVR. OBJECTIVES: This study aims to investigate the cardiac damage trajectories following TAVR and explore their association with subsequent clinical outcomes. METHODS: AS patients undergoing TAVR were enrolled and classified into five cardiac damage stages (0-4) based on the echocardiographic staging classification retrospectively. They were further grouped into early stage (stage 0-2) and advanced stage (stage 3-4). The cardiac damage trajectories in TAVR recipients were evaluated according to their trend between baseline and 30 days after TAVR. RESULTS: A total of 644 TAVR recipients were enrolled, with four distinct trajectories identified. Compared to patients with early-early trajectory, patients with early-advanced trajectory were at 30-fold risk of all-cause death (HR 30.99, 95% CI 13.80-69.56; p < 0.001). In multivariable analyses, early-advanced trajectory was associated with higher 2-year all-cause death (HR 24.08, 95% CI 9.07-63.90; p < 0.001), cardiac death (HR 19.34, 95% CI 3.06-122.34; p < 0.05), and cardiac rehospitalization (HR 4.19, 95% CI 1.49-11.76; p < 0.05) after TAVR. CONCLUSIONS: This investigation provided insight into four cardiac damage trajectories in TAVR recipients and confirmed the prognostic value of distinct trajectories. Early-advanced trajectory was associated with poor clinical prognosis following TAVR.

Impact of early changes in cardiac damage following transcatheter aortic valve implantation.

BACKGROUND: The staging classification of aortic stenosis (AS) which characterises the extent of cardiac damage has been validated in patients undergoing transcatheter aortic valve implantation (TAVI). Short-term changes in cardiac damage after TAVI and their association with long-term prognosis remain unknown. AIMS: This study aims to investigate the early evolution of cardiac damage after TAVI and the association of residual cardiac damage with clinical outcomes in TAVI recipients. METHODS: AS patients undergoing TAVI were consecutively enrolled and classified into five stages of cardiac damage (0-4). Early change in cardiac damage was defined as any change of stage at 30 days (Δcardiac damage between baseline pre-TAVI and 30 days post-TAVI). RESULTS: Within 30 days post-TAVI, the baseline cardiac damage stage had changed in 22.2% of 644 TAVI recipients, accompanied by improvements in the degree of dyspnoea and left ventricular ejection fraction (LVEF). Two-year mortality was associated with residual cardiac damage within 30 days post-TAVI (hazard ratio [HR] 2.97, 95% confidence interval [CI]: 2.07-4.25; p<0.001). Compared to unchanged cardiac damage post-TAVI, further cardiac damage within 30 days was associated with a higher crude risk of 2-year mortality (HR 22.04, 95% CI: 9.87-49.20; p<0.001). Cardiac deterioration within 30 days post-TAVI was an independent risk factor for 2-year mortality (HR 19.564, 95% CI: 8.047-47.565; p<0.001). CONCLUSIONS: This investigation provided insight into the early evolution of cardiac damage in TAVI recipients and confirmed the predictive value of both residual and early changes in cardiac damage post-TAVI. Cardiac deterioration within 30 days is associated with poor clinical prognosis.

NT-proBNP trajectory after transcatheter aortic valve replacement and its association with 5-year clinical outcomes.

Background: There are only limited reports on the trends of NT-proBNP after transcatheter aortic valve replacement (TAVR) in aortic stenosis (AS) and even fewer report on the prognostic value of the NT-proBNP trajectory following TAVR. Objectives: This study aims to investigate short-term NT-proBNP trajectory following TAVR and explore its association with clinical outcomes in TAVR recipients. Methods: Aortic stenosis patients undergoing TAVR were included if they had NT-proBNP levels recorded at baseline, prior to discharge, and within 30 days after TAVR. We used latent class trajectory models to identify NT-proBNP trajectories based on their trends over time. Results: Three distinct NT-proBNP trajectories were identified from 798 TAVR recipients, which were named class 1 (N = 661), class 2 (N = 102), and class 3 (N = 35). Compared to those with trajectory class 1, patients with trajectory class 2 had a more than 2.3-fold risk of 5-year all-cause death and 3.4-fold risk of cardiac death, while patients with trajectory class 3 had a more than 6.6-fold risk of all-cause death and 8.8-fold risk of cardiac death. By contrast, the groups had no differences in 5-year hospitalization rates. In multivariable analyses, the risk of 5-year all-cause mortality was significantly higher in patients with trajectory class 2 (HR 1.90, 95% CI 1.03-3.52, P = 0.04) and class 3 (HR 5.70, 95% CI 2.45-13.23, P < 0.01). Conclusion: Our findings implied different short-term evolution of NT-proBNP levels in TAVR recipients and its prognostic value for AS patients following TAVR. NT-proBNP trajectory may have further prognostic value, in addition to its baseline level. This may aid clinicians with regards to patient selection and risk prediction in TAVR recipients.

MicroRNA-455-3p accelerate malignant progression of tumor by targeting H2AFZ in colorectal cancer.

Colorectal cancer (CRC) becomes the second leading cause of cancer-related deaths in 2020. Emerging studies have indicated that microRNAs (miRNAs) play a key role in tumorigenesis and progression. The dysfunctions of miR-455-3p are observed in many cancers. However, its biological function in CRC remains to be confirmed. By sequencing serum sample, miR-455-3p was found to be up-regulated in CRC patients. RT-qPCR demonstrated that the miR-455-3p expression was both higher in the serum and tumor tissues of CRC patients. Furthermore, it indicated that miR-455-3p had the ability in promoting cell proliferation, suppressing cell apoptosis, and stimulating cell migration. In vivo experiments also showed that miR-455-3p promoted tumor growth. Additionally, H2AFZ was proved as the direct gene target of miR-455-3p by dual-luciferase assay. Taken together, miR-455-3p functioned as a tumor promoter in CRC development by regulating H2AFZ directly. Thus, it has enormous potential as a biomarker in the diagnosis of CRC.

Mitochondria-targeting nanozyme alleviating temporomandibular joint pain by inhibiting the TNFα/NF-κB/NEAT1 pathway.

Inflammatory cytokines that are secreted into the spinal trigeminal nucleus caudalis (Sp5C) may augment inflammation and cause pain associated with temporomandibular joint disorders (TMD). In a two-step process, we attached triphenylphosphonium (TPP) to the surface of a cubic liposome metal-organic framework (MOF) loaded with ruthenium (Ru) nanozyme. The design targeted mitochondria and was designated Mito-Ru MOF. This structure scavenges free radicals and reactive oxygen species (ROS) and alleviates oxidative stress. The present study aimed to investigate the effects and mechanisms by which Mito-Ru MOF ameliorates TMD pain. Intra-temporomandibular joint (TMJ) injections of complete Freund's adjuvant (CFA) induced inflammatory pain for ≥10 d in the skin areas innervated by the trigeminal nerve. Tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1), and ROS also have been proved to be significantly upregulated in the Sp5C of TMD mice. Moreover, a single Mito-Ru MOF treatment alleviated TMD pain for 3 d and downregulated TNF-α, NF-κB, lncRNA NEAT1, and ROS. NF-κB knockdown downregulated NEAT1 in the TMD mice. Hence, Mito-Ru MOF inhibited the production of ROS and alleviated CFA-induced TMD pain via the TNF-α/NF-κB/NEAT1 pathway. Therefore, Mito-Ru MOF could effectively treat the pain related to TMD and other conditions associated with severe acute inflammatory activation.

Correction: Mitochondria-targeting nanozyme alleviating temporomandibular joint pain by inhibiting the TNFα/NF-κB/NEAT1 pathway.

Correction for 'Mitochondria-targeting nanozyme alleviating temporomandibular joint pain by inhibiting the TNFα/NF-κB/NEAT1 pathway' by Qian Bai et al., J. Mater. Chem. B, 2023, https://doi.org/10.1039/d3tb00929g.

Improving the Transglycosylation Activity of α-Glucosidase from Xanthomonas campestris Through Semi-rational Design for the Synthesis of Ethyl Vanillin-α-Glucoside.

The α-glucosidase (EC 3.2.1.20) XgtA produced by Xanthomonas campestris shows high α-glucosyl transfer activity toward alcoholic and phenolic hydroxyl groups. Ethyl vanillin-α-glucoside, a precursor-aroma compound with improved water solubility and thermal stability, can be synthesized through the transglycosylation of ethyl vanillin by XgtA. However, its low ethyl vanillin-α-glucoside yield and ability to hydrolyze ethyl vanillin-α-glucoside limits for industrial applications. Rational design and site-directed mutagenesis were employed to generate three variants of X. campestris α-glucosidase, L145I, S272T, and L145I/S272T, with improved transglycosylation activity toward EV. The highest yield is up to 52.41% by L145I/S272T, which also displayed remarkably lower hydrolysis activity toward the glycoside product EVG compared to XgtA. These results also showed that the mutation in sugar-binding subsite + 1 is more effective than subsite -1 for enhancing the ratio of transglycosylation/hydrolysis for the α-glucosidase XgtA.

Effects of Different Pesticides on the Brewing of Wine Investigated by GC-MS-Based Metabolomics.

The application of pesticides is critical during the growth of high-quality grape for wine making. However, pesticide residues have significant influence on the wine flavor. In this study, gas chromatography-mass spectrometry (GC-MS) was performed and the obtained datasets were analyzed with multivariate statistical methods to investigate changes in flavor substances in wine during fermentation. The principal component analysis (PCA) score plot showed significant differences in the metabolites of wine treated with various pesticides. In trials using five pesticides (hexaconazole, difenoconazole, flutriafol, tebuconazole, and propiconazole), more than 86 metabolites were changed. Most of these metabolites were natural flavor compounds, like carbohydrates, amino acids, and short-chain fatty acids and their derivatives, which essentially define the appearance, aroma, flavor, and taste of the wine. Moreover, the five pesticides added to grape pulp exhibited different effects on the metabolic pathways, involving mainly alanine, aspartate and glutamate metabolism, butanoate metabolism, arginine, and proline metabolism. The results of this study will provide new insight into the potential impact of pesticide residues on the metabolites and sensory profile of wine during fermentation.