Based on metabolomics, chemometrics, and modern separation omics: Identifying key in-pathway and out-pathway points for pesticide residues during solid-state fermentation of baijiu.

By collecting real samples throughout the entire production process and employing chemometrics, metabolomics, and modern separation omic techniques, it unveiled the patterns of pesticide transfer during solid-state fermentation. The results indicated that 12 types of pesticide residues were prevalent during baijiu production, with organochlorine and carbamate pesticides being the most abundant in raw materials. After fermentation, organochlorine pesticides and pyrethroid pesticides exhibited higher content, while carbamate pesticides dominated in the final product. The pathways for pesticide input and elimination were identified, and the intricate mechanisms underlying these changes were further elucidated. Additionally, key control points were defined to facilitate targeted monitoring. The results indicated that pesticide residue primarily originates from raw materials and Daqu, whereas both solid-state fermentation and distillation processes were effective in reducing pesticide residues. The study offers valuable guidance for establishing pesticide residue standards in the context of baijiu production.

Investigation of interactions between Jiuzao glutelin with resveratrol, quercetin, curcumin, and azelaic and potential improvement on physicochemical properties and antioxidant activities.

The interactions among small molecular functional components (FCTs) within a food matrix have become a focal point for enhancing their stability and bioactivities. Jiuzao glutelin (JG) is a mixed plant protein within Jiuzao (a protein-rich baijiu distillation by-product). This study aimed to explore the interactions between JG and selected FCTs, including resveratrol (RES), quercetin (QUE), curcumin (CUR), and azelaic acid (AZA), and the consequential impact on stability and antioxidant activity of the complexes. The findings conclusively demonstrated that the interactions between JG and the FCTs significantly enhanced the storage stability of the complexes. Moreover, the antioxidant activity of the complexes exhibited improvement compared to their individual counterparts. This study underscores the notion that JG and FCTs mutually reinforce, exerting positive effects on stability and antioxidant activity. This symbiotic relationship can be strategically employed to augment the quality of proteins and enhance the functional properties of bioactive components through these interactions.

International Normalized Ratio Predicts Recurrence and Bleeding in Patients With Acute Venous Thromboembolism Who Undergo Direct Oral Anticoagulants.

Prothrombin time/international normalized ratio (PT/INR) is related to both antithrombotic effect and risk of bleeding. Its role in the prediction of venous thromboembolism (VTE) recurrence and bleeding for patients with acute VTE who undergo direct oral anticoagulants (DOACs) treatment is unclear, despite previous studies revealed some association between them. The predictive efficiency of INR for VTE recurrence and bleeding were analyzed in a retrospective cohort with VTE patients who underwent DOACs treatment. Then its predictive efficiency for VTE recurrence and bleeding were validated in a prospective cohort with the acquired cutoffs range, and compared with anti-Xa level, DASH and VTE-BLEED scores. In the retrospective cohort (n = 1083), the sensitivity and specificity of INR for the prediction of VTE recurrence were 79.4% and 92.8%, respectively. The area under the curve (AUC) was 0.881 (0.803-0.960)(P = .025). The cutoff value of INR was 0.9. The sensitivity and specificity of INR for the prediction of bleeding were 85.7% and 77.9%, respectively. The AUC was 0.876 (0.786-0.967)(P < .001). The cutoff value of INR was 2.1. In the prospective cohort (n = 202), the calibration showed that there were 4 (50%) patients with VTE recurrence, 156 (97.5%) patients with non-recurrence and bleeding (non-R&B), and 20 (58.8%) patients with bleeding in the low (INR < 0.9)(n = 8), intermediate (0.9 ≤ INR ≤ 2.1)(n = 160), and high (INR > 2.1)(n = 34) groups, respectively. The baseline PT/INR value at the initiation of DOACs treatment is an independent predictor for VTE recurrence and bleeding in patients with acute VTE who undergo DOACs treatment.

Construction of resveratrol and quercetin nanoparticles based on folic acid targeted Maillard products between Jiuzao glutelin isolate and carboxymethyl chitosan: Improved stability and function.

Advanced targeted nanoparticles (NPs) were designed to enhance the targeted delivery of resveratrol (RES) and quercetin (QUE) by utilizing carboxymethyl chitosan (CTS) and Jiuzao glutelin isolate (JGI) conjugates. Briefly, RES and QUE were encapsuled within CTS-JGI-2 (CTS/JGI, m/m, 2:1). The carrier's targeting properties were further improved through the incorporation of folic acid (FA) and polyethylenimine (PEI). Moreover, the stability against digestion was enhanced by incorporating baker yeast cell walls (BYCWs) to construct RES-QUE/FA-PEI/CTS-JGI-2/MAT/BYCW NPs. The results demonstrated that FA-PEI/CTS-JGI-2/MAT/BYCW NPs could improve cellular uptake and targeting property of RES and QUE through endocytosis of folic acid receptors (FOLRs). Additionally, RES-QUE successfully alleviated LPS- and DSS-induced inflammation by regulating NF-κB/IkBa/AP-1 and AMPK/SIRT1signaling pathways and reducing the secretion of inflammatory mediators and factors. These findings indicate FA-PEI/CTS-JGI-2/MAT/BYCW NPs hold promise as an oral drug delivery system with targeted delivery capacities for functional substances prone to instability in dietary supplements.

Computational Enzyme Redesign Enhances Tolerance to Denaturants for Peptide C-Terminal Amidation.

The escalating demand for biocatalysts in pharmaceutical and biochemical applications underscores the critical imperative to enhance enzyme activity and durability under high denaturant concentrations. Nevertheless, the development of a practical computational redesign protocol for improving enzyme tolerance to denaturants is challenging due to the limitations of relying solely on model-driven approaches to adequately capture denaturant-enzyme interactions. In this study, we introduce an enzyme redesign strategy termed GRAPE_DA, which integrates multiple data-driven and model-driven computational methods to mitigate the sampling biases inherent in a single approach and comprehensively predict beneficial mutations on both the protein surface and backbone. To illustrate the methodology's effectiveness, we applied it to engineer a peptidylamidoglycolate lyase, resulting in a variant exhibiting up to a 24-fold increase in peptide C-terminal amidation activity under 2.5 M guanidine hydrochloride. We anticipate that this integrated engineering strategy will facilitate the development of enzymatic peptide synthesis and functionalization under denaturing conditions and highlight the role of engineering surface residues in governing protein stability.

[Structure motif guided mining of MHET hydrolase and development of a two-enzyme cascade for plastics depolymerization at mild temperature].

The utilization of polyethylene terephthalate (PET) has caused significant and prolonged ecological repercussions. Enzymatic degradation is an environmentally friendly approach to addressing PET contamination. Hydrolysis of mono(2-hydroxyethyl) terephthalate (MHET), a competitively inhibited intermediate in PET degradation, is catalyzed by MHET degrading enzymes. Herein, we employed bioinformatic methods that combined with sequence and structural information to discover an MHET hydrolase, BurkMHETase. Enzymatic characterization showed that the enzyme was relatively stable at pH 7.5-10.0 and 30-45 ℃. The kinetic parameters kcat and Km on MHET were (24.2±0.5)/s and (1.8±0.2) µmol/L, respectively, which were similar to that of the well-known IsMHETase with higher substrate affinity. BurkMHETase coupled with PET degradation enzymes improved the degradation of PET films. Structural analysis and mutation experiments indicated that BurkMHETase may have evolved specific structural features to hydrolyze MHET. For MHET degrading enzymes, aromatic amino acids at position 495 and the synergistic interactions between active sites or distal amino acids appear to be required for MHET hydrolytic activity. Therefore, BurkMHETase may have substantial potential in a dual-enzyme PET degradation system while the bioinformatic methods can be used to broaden the scope of applicable MHETase enzymes.

Current situation, trend, and prospects of research on functional components from by-products of baijiu production: A review.

In the present scenario marked by energy source shortages and escalating concerns regarding carbon dioxide emissions, there is a growing emphasis on the optimal utilization of biomass resources. Baijiu, as the Chinese national spirit, boasts remarkably high sales volumes annually. However, the production of baijiu yields various by-products, including solid residues (Jiuzao), liquid wastewater (Huangshui and waste alcohol), and gaseous waste. Recent years have witnessed dedicated research aimed at exploring the composition and potential applications of these by-products, seeking sustainable development and comprehensive resource utilization. This review systematically summarizes recent research, shedding light on both the baijiu brewing process and the bioactive compounds present baijiu production by-products (BPBPs). The primary focus lies in elucidating the potential extraction methods and applications of BPBPs, offering a practical approach to comprehensive utilization of by-products in functional food, medicine, cosmetic, and packaging fields. These applications not only contribute to enhancing production efficiency and mitigating environmental pollution, but also introduce innovative concepts for the sustainable advancement of associated industries. Future research avenues may include more in-depth compositional analysis, the development of utilization technologies, and the promotion of potential industrialization.

Computational redesign of a hydrolase for nearly complete PET depolymerization at industrially relevant high-solids loading.

Biotechnological plastic recycling has emerged as a suitable option for addressing the pollution crisis. A major breakthrough in the biodegradation of poly(ethylene terephthalate) (PET) is achieved by using a LCC variant, which permits 90% conversion at an industrial level. Despite the achievements, its applications have been hampered by the remaining 10% of nonbiodegradable PET. Herein, we address current challenges by employing a computational strategy to engineer a hydrolase from the bacterium HR29. The redesigned variant, TurboPETase, outperforms other well-known PET hydrolases. Nearly complete depolymerization is accomplished in 8 h at a solids loading of 200 g kg-1. Kinetic and structural analysis suggest that the improved performance may be attributed to a more flexible PET-binding groove that facilitates the targeting of more specific attack sites. Collectively, our results constitute a significant advance in understanding and engineering of industrially applicable polyester hydrolases, and provide guidance for further efforts on other polymer types.

Inhibitory Effects of Jiuzao Polysaccharides on Alcoholic Fatty Liver Formation in Zebrafish Larvae and Their Regulatory Impact on Intestinal Microbiota.

The liver is critical in alcohol metabolism, and excessive consumption heightens the risk of hepatic damage, potentially escalating to hepatitis and cirrhosis. Jiuzao, a by-product of Baijiu production, contains a rich concentration of naturally active polysaccharides known for their antioxidative properties. This study investigated the influence of Laowuzeng Jiuzao polysaccharide (LJP) on the development of ethanol-induced alcoholic fatty liver. Zebrafish larvae served as the model organisms for examining the LJPs hepatic impact via liver phenotypic and biochemical assays. Additionally, this study evaluated the LJPs effects on gene expression associated with alcoholic fatty liver and the composition of the intestinal microbiota through transcriptomic and 16 S rRNA gene sequencing analyses, respectively. Our findings revealed that LJP markedly mitigated morphological liver damage and reduced oxidative stress and lipid peroxidation in larvae. Transcriptome data indicated that LJP ameliorated hepatic fat accumulation and liver injury by enhancing gene expression involved in alcohol and lipid metabolism. Furthermore, LJP modulated the development of alcoholic fatty liver by altering the prevalence of intestinal Actinobacteriota and Firmicutes, specifically augmenting Acinetobacter while diminishing Chryseobacterium levels. Ultimately, LJP mitigated alcohol-induced hepatic injury by modulating gene expression related to ethanol metabolism, lipid metabolism, and inflammation and by orchestrating alterations in the intestinal microbiota.

Characterization of key aroma compounds in soy sauce flavor baijiu by molecular sensory science combined with aroma active compounds reverse verification method.

The distinctive flavor profile of soy sauce flavor baijiu (SAB) is shaped by its unique aroma compounds. The characteristic aroma compounds in Langjiu soy sauce flavor baijiu (LSAB) were explored based on molecular sensory science. A total of 66 aroma active compounds were identified by gas chromatography-olfactometry (GC-O) combined with aroma extract dilution analysis (AEDA), and 6 important unknown sulfur compounds were identified using the aroma active compounds reverse verification method (ACRVW). A total of 39 key aroma compounds were determined to have odor activity values (OAVs) ≥ 1. The aroma contribution of aroma components was verified by aroma recombination and aroma omission experiments. 15 characteristic aroma compounds were identified in LSAB. Meanwhile, a simple and easy-to-understand sensory expression language was described to fully understand the style characteristics of LSAB. Overall, the present paper offers insights into research uncovering the key "sauce flavor" of soy sauce flavor baijiu.

Effect of Different Ethylene Oxide Addition Numbers on the Performance of Polyoxyethylene Tallow Amine as a Pesticide Emulsifier.

Surfactant reduces the surface tension of liquids, resulting in improved emulsion stability, and there is great interest in pesticide additives. Ethoxylate is often used as a pesticide emulsifier. However, the degree of ethoxylation and the existence of dioxane byproducts can significantly affect the performance of emulsifiers. Here, a series of polyoxyethylene tallow amines with the addition of different numbers of ethylene oxide (EO) were synthesized and characterized. Their physical and chemical performances were measured. The ability of POEA as a surfactant to reduce water surface tension and the surface adsorption of molecules were assessed based on the static and dynamic surface tensions. The results show that the surfactant molecules preferentially form a saturated adsorption layer in solution, and the mixed-diffusion-kinetics mechanism dominates the adsorption process. With the increase of the EO addition number, the emulsifying property of POEA increases, while the wetting property gradually decreases and the contact angle increases. These results can provide a basis for the selection of pesticide additives. At the same time, the mechanism of removing dioxane by ethoxylate is described, and a simple and low-consumption method is put forward to reduce the dioxane content. It provides a new idea for the removal of dioxane.

The Legend score synthesizes Wells, PERC, Geneva, D-dimer and predicts acute pulmonary embolism prior to imaging tests.

INTRODUCTION: The prediction rules of acute pulmonary embolism(PE) before imaging tests recommended by the commonly used guidelines have low diagnostic efficiency if not combined with D-dimer, therefore it is necessary to seek for a prediction rule with higher diagnostic efficiency. METHODS: We designed a new score named Legend by synthesizing the scores of Wells, PERC, and Geneva, as well as D-dimer with patients in the development group(n = 2112), and then validated it in patients of validation group(n = 388). Diagnostic efficiency was also compared between Legend score and Wells+D-dimer (DD), PERC+DD, Geneva+DD, and YEARS+DD(YEAR algorithm). RESULTS: The Legend score comprised active cancer, D-dimer≥1000 ng/mL, DVT symptoms and/or signs, previous venous thromboembolism (VTE) history, and surgery, trauma, or immobilization in the past month. The sensitivity, specificity, Youden index, and area under the curve(AUC) were 0.985, 0.744, 0.729, and (0.861[0.796-0.925], P<0.001), respectively, for original Legend score, whereas were 0.982, 0.778, 0.760, and (0.871[0.823-0.920], P<0.001), respectively, for simplified Legend score. The Kappa coefficient and P value of McNemar test were 0.988 and 1.000, respectively, between the original and simplified Legend scores. In the validation group, the sensitivity, specificity, Youden index, and C-index were 0.971, 0.749, 0.720, and (0.838[0.781-0.896], P<0.001), respectively, for the original Legend score, whereas were 0.986, 0.715, 0.701, and (0.816[0.750-0.880], P = 0.001) respectively, for the simplified Legend score. The Kappa coefficient and P value of McNemar test between original Legend score and Wells+DD, PERC+DD, Geneva+DD, and YEARS+DD were (0.563, 0.001), (0.139, <0.001), (0.631, 0.006), and (0.732, 0.029), respectively. The Kappa coefficient and P value of McNemar test between simplified Legend score and aforementioned scores were (0.675, 0.009), (0.172, <0.001), (0.747, 0.001), and (0.883, 0.012), respectively. DISCUSSION: In view of the fact the Legend score reserves the efficient predictors and eliminates the inefficient ones in Wells, PERC, and revised Geneva scores, and incorporates D-dimer into it, a more efficient, modified, and user-friendly one has replaced the original ones. CONCLUSIONS: The Legend score yields excellent diagnostic efficiency with good safety in the pretest prediction of acute PE prior to imaging tests. It also avoids more unnecessary imaging tests than Wells+DD, PERC+DD, Geneva+DD, or YEARS+DD.

Obstructive sleep apnea promotes the progression of lung cancer by modulating cancer cell invasion and cancer-associated fibroblast activation via TGFß signaling.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with severity of pneumonia; however, the mechanism by which OSA promotes lung cancer progression is unclear. METHODS: Twenty-five lung cancer patients were recruited to investigate the relationship between OSA and cancer-associated fibroblast (CAFs) activation. Lung cancer cells (A549) and WI38 fibroblast cells were used to explore the hypoxia-induced TGFß expression using qPCR, Western blot, and ELISA. Wound healing and transwell assays were performed to evaluate cancer cell migration and invasion. A549 or A549-Luc + WI38 xenograft mouse models were established to detect the intermittent hypoxia (IH) associated with lung tumor growth and epithelial-mesenchymal transition (EMT) in vivo. RESULTS: OSA promotes CAF activation and enrichment in lung cancer patients. Hypoxia (OSA-like treatment) activated TGFß signaling in both lung cancer cells and fibroblasts, which promoted cancer cell migration and invasion, and enriched CAFs. IH promoted the progression and EMT process of lung cancer xenograft tumor. Co-inoculation of lung cancer cells and fibroblast cells could further promote lung cancer progression. CONCLUSIONS: IH promotes lung cancer progression by upregulating TGFß signaling, promoting lung cancer cell migration, and increasing the CAF activation and proportion of lung tumors.

Characterization and stability investigation of rhein encapsulated microcapsules using different enteric biopolymers with pullulan and Jiuzao glutelin conjugates via Maillard reaction.

The poor water solubility and rhein (RH) stability limit its application in the functional food industry. In the present study, the RH-loaded water-in-oil-in-water nano emulsion and microcapsules were prepared using the conjugates of pullulan-Jiuzao glutelin (JG) (m/m, 2:1, PJC-2) obtained by Maillard reaction and enteric-soluble materials (polymethlacrylic acid, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, and D-mannitol). The effects of different formulations on the microstructure, physicochemical properties, and storage stability of microcapsules were analyzed. The results showed that microcapsules exhibited stability against different external environments. The encapsulation efficiency of RH in the four enteric-soluble-PJC-2 double-deck microcapsules (70.03 ± 3.24%-91.08 ± 4.78%) was significantly improved than PJC-2 ones (61.84 ± 0.47%). The antioxidant activity and stability of RH in the microcapsules were improved (ABTS, 49.7%-113.93%; DPPH, 40.85%-101.82%; FRA, 62.32%-126.42%; and FCA, 70.58%-147.20%) after in vitro simulated digestion and extreme environmental conditions compared to free RH. This work provides a microcapsule based on PJC-2 with enteric-soluble materials for insoluble functional ingredients to improve solubility, stability, and bioactivity in the food industry.

Allosteric switch for electrochemical aptasensor toward heavy metals pollution of Lentinus edodes sensitized with porphyrinic metal-organic frameworks.

BACKGROUND: Lentinan medicament from Lentinus edodes has been considered as natural medicinal products with minimal side effects for cancer therapy, but Lentinus edodes are easily polluted by nonbiodegradable heavy metals, especially silver ion (Ag+). Therefore, it is highly desirable to monitor Ag + pollution in Lentinus edodes considering their adverse impact on lentinan medicament. Electrochemical sensor isn't affected from the interference of matrix turbidity and color, and offers a powerful means for determination of variant analytes. As for electrochemical sensing toward Ag+, there is a great need to design efficient signal probes for specific recognition and signal generation. RESULTS: We present an appropriate electrochemical aptasensor for Ag + assay based on biomimetic catalysis of porphyrin-encapsulated MOF (PorMOF) and allosteric switch of C-rich DNA. Thanks to the excellent biocompatibility, PorMOFs as nanozyme are used to design signal probes by loading duplex-like DNA scaffold. Owing to the specific recognition of Ag+ toward cytosine (C) base-rich DNA, PorMOF at the distal end was close to the underlying electrode via C-Ag+-C formation, leading to an enhanced current of catalytic hydroxylamine oxidation for signal generation. Using the positive correlation between current response and Ag+ level, the electrochemical system provides a promising means for on-line monitoring of Ag+ in Lentinus edodes with recoveries from 92.8% to 106.4% and relative standard deviation from 3.98% to 8.24%, verifying the applicability of the electrochemical aptasensor toward Ag+ in Lentinus edodes. SIGNIFICANCE AND NOVELTY: With merits of portability, simple operation, and rapid response, the electrochemical pattern offers a useful solution for on-line monitoring of Ag+ in Lentinus edodes. By altering the DNA sequence, the proposed aptasensor provides a powerful way for monitoring other heavy metals, capable of protecting medicament production from heavy metal pollution.

Unravelling Metabolic Heterogeneity of Chinese Baijiu Fermentation in Age-Gradient Vessels.

Fermentation vessels affect the characteristics of food fermentation; however, we lack an approach to identify the biomarkers indicating fermentation. In this study, we applied metabolomics and high-throughput sequencing analysis to reveal the dynamic of metabolites and microbial communities in age-gradient fermentation vessels for baijiu production. Furthermore, we identified 64 metabolites during fermentation, and 19 metabolites significantly varied among the three vessels (p < 0.05). Moreover, the formation of these 19 metabolites were positively correlated with the core microbiota (including Aspergillus, Saccharomyces, Lactobacillus, and Bacillus). In addition, ethyl lactate or ethyl acetate were identified as the biomarkers for indicating the metabolism among age-gradient fermentation vessels by BP-ANN (R2 > 0.40). Therefore, this study combined the biological analysis and predictive model to identify the biomarkers indicating metabolism in different fermentation vessels, and it also provides a potential approach to assess the profiling of food fermentations.

Integration of Chemometrics and Sensory Metabolomics to Validate Quality Factors of Aged Baijiu (Nianfen Baijiu) with Emphasis on Long-Chain Fatty Acid Ethyl Esters.

The storage process of Baijiu is an integral part of its production (the quality undergoes substantial changes during the aging process of Baijiu). As the storage time extends, the flavor compounds in Baijiu tend to undergo coordinated transformation, thereby enhancing the quality of Baijiu. Among them, long-chain fatty acid ethyl esters (LCFAEEs) were widely distributed in Baijiu and have been shown to have potential contributions to the quality of Baijiu. However, the current research on LCFAEEs in Baijiu predominantly focuses on the olfactory sensation aspect, while there is a lack of systematic investigation into their influence on taste and evaluation after drinking Baijiu during the aging process. In light of this, the present study investigates the distribution of LCFAEEs in Baijiu over different years. We have combined modern flavor sensory analysis with multivariate chemometrics to comprehensively and objectively explore the influence of LCFAEEs on Baijiu quality. The results demonstrate a significant positive correlation between the concentration of LCFAEEs and the fruity aroma (p < 0.05, r = 0.755) as well as the aged aroma (p < 0.05, r = 0.833) of Baijiu within a specific range; they can effectively reduce the off-flavors and spicy sensation of Baijiu. Furthermore, additional experiments utilizing a single variable suggest that LCFAEEs were crucial factors influencing the flavor of Baijiu, with Ethyl Palmitate (EP) being the most notable LCFAEE that merits further systematic investigation.

zPoseScore model for accurate and robust protein-ligand docking pose scoring in CASP15.

We introduce a deep learning-based ligand pose scoring model called zPoseScore for predicting protein-ligand complexes in the 15th Critical Assessment of Protein Structure Prediction (CASP15). Our contributions are threefold: first, we generate six training and evaluation data sets by employing advanced data augmentation and sampling methods. Second, we redesign the "zFormer" module, inspired by AlphaFold2's Evoformer, to efficiently describe protein-ligand interactions. This module enables the extraction of protein-ligand paired features that lead to accurate predictions. Finally, we develop the zPoseScore framework with zFormer for scoring and ranking ligand poses, allowing for atomic-level protein-ligand feature encoding and fusion to output refined ligand poses and ligand per-atom deviations. Our results demonstrate excellent performance on various testing data sets, achieving Pearson's correlation R = 0.783 and 0.659 for ranking docking decoys generated based on experimental and predicted protein structures of CASF-2016 protein-ligand complexes. Additionally, we obtain an averaged local distance difference test (lDDT pli = 0.558) of AIchemy LIG2 in CASP15 for de novo protein-ligand complex structure predictions. Detailed analysis shows that accurate ligand binding site prediction and side-chain orientation are crucial for achieving better prediction performance. Our proposed model is one of the most accurate protein-ligand pose prediction models and could serve as a valuable tool in small molecule drug discovery.

Optimal length of oral anticoagulant treatment for maximum benefit within 5 years after discontinuation of oral anticoagulants in patients with acute pulmonary embolism who require secondary thromboprophylaxis.

BACKGROUND: Extended oral anticoagulant (OA) use is recommended in patients with acute pulmonary embolism (PE) who require secondary thromboprophylaxis. Nevertheless, the optimal length of OA use for the maximum long-term benefit in this patient population has been undefined to date. METHODS: A retrospective study was performed to explore the role of different length of overall OA use (group 1 (≥1 year of OA use and <2 years of OA use), group 2 (≥2 years of OA use and <3 years of OA use), group 3 (≥ 3 years of OA use)) in outcomes within 5 years after OA discontinuation in patients with acute PE, who required secondary thromboprophylaxis. The primary outcome was mortality rates. The secondary outcomes comprised venous thromboembolism (VTE) recurrence, major bleeding during OA use and net clinical benefit. Net clinical benefit was defined as the composite of recurrent VTE and major bleeding. RESULTS: For a total of 385 patients in group 1 (n=220), group 2 (n=110) and group 3 (n=55), the PE-related mortality in group 1 was higher than that in group 2 (p=0.034) and 3 (p=0.040), respectively, whereas were similar between groups 2 and 3 (p=1.000). The net clinical benefit in group 1 was less than that in group 2 (p=0.024), whereas similar with that in group 3 (p=0.526). The net clinical benefit was comparable between groups 2 and 3 (p=0.716). The length of OA use was positively associated with major bleeding (HR, 2.510 (0.293 to 3.485), p=0.001), whereas negatively associated with PE-related mortality (HR, 0.668 (0.196 to 2.832), p=0.025) and VTE recurrence (HR, 0.694 (0.174 to 2.300), p=0.036), respectively. The sensitivity and specificity of the length of OA use for the tendency of PE-related mortality was 70.2% and 46.2%, respectively. The area under the curve (AUC) was 0.654 (0.514 to 0.793) (p=0.029). The sensitivity and specificity of the length of OA use for the tendency of net clinical benefit was 86.8% and 64.3%, respectively. The AUC was 0.628 (0.565 to 0.690) (p<0.001) CONCLUSIONS: For patients with acute PE who require secondary thromboprophylaxis, 2 to 3 years (30 months preferred) of overall OA use after a diagnosis of acute PE could be an optimal length to achieve maximum benefit within 5 years after OA discontinuation.

Identification of regionalmarkers based on the flavor molecular matrix analysis of sauce-aroma style baijiu.

BACKGROUND: Baijiu is a very complex system and its flavor substances are endogenous, influenced by raw materials, starter, production process, production region and other factors. The production region directly affects the composition of flavor substances and quality of baijiu. However, identification of baijiu region is challenging because the corresponding relationship between the production region and baijiu quality is not clear, and the identification of regionalmarkers is indeterminate. In this study, the differences in volatile components of sauce-aroma style baijiu from four representative regions were investigated. RESULTS: A total of 94 volatile compounds were identified in samples tested. Additionally, it was verified that 35 potential flavor substances had important contributions to the aroma of sauce-aroma style baijiu. Meanwhile, nine potential regionalmarkers were screened through multivariate analysis. Further, based on distribution of volatile compounds and the results of sensory evaluation combined with multivariate analysis, a molecular matrix and correlation network were established according to the results of addition experiments, which showed that six substances had a significant impact on the flavor of the tested samples. CONCLUSION: Six key flavor substances (ethyl octanoate, ethyl 2-methylpropanoate, propyl acetate, ethyl heptanoate, 2-nonanone and butyl hexanoate) were considered as important regionalmarkers to effectively identify the production region of sauce-aroma style baijiu. © 2023 Society of Chemical Industry.