Microbial succession and its effect on the formation of umami peptides during sufu fermentation

Sufu, a traditional Chinese fermented food, is famous for its unique flavor, especially umami. However, the formation mechanism of its umami peptides is still unclear. Here, we investigated the dynamic change of both umami peptides and microbial communities during sufu production. Based on peptidomic analysis, 9081 key differential peptides were identified, which mainly involved in amino acid transport and metabolism, peptidase activity and hydrolase activity. Twenty-six high-quality umami peptides with ascending trend were recognized by machine learning methods and Fuzzy c-means clustering. Then, through correlation analysis, five bacterial species (Enterococcus italicus, Leuconostoc citreum, L. mesenteroides, L. pseudomesenteroides, Tetragenococcus halophilus) and two fungi species (Cladosporium colombiae, Hannaella oryzae) were identified to be the core functional microorganisms for umami peptides formation. Functional annotation of five lactic acid bacteria indicated their important functions to be carbohydrate metabolism, amino acid metabolism and nucleotide metabolism, which proved their umami peptides production ability. Overall, our results enhanced the understanding of microbial communities and the formation mechanism of umami peptides in sufu, providing novel insights for quality control and flavor improvement of tofu products

Informer: Beyond Efficient Transformer for Long Sequence Time-Series Forecasting

Many real-world applications require the prediction of long sequence time-series, such as electricity consumption planning. Long sequence time-series forecasting (LSTF) demands a high prediction capacity of the model, which is the ability to capture precise long-range dependency coupling between output and input efficiently. Recent studies have shown the potential of Transformer to increase the prediction capacity. However, there are several severe issues with Transformer that prevent it from being directly applicable to LSTF, including quadratic time complexity, high memory usage, and inherent limitation of the encoder-decoder architecture. To address these issues, we design an efficient transformer-based model for LSTF, named Informer, with three distinctive characteristics: (i) a $ProbSparse$ self-attention mechanism, which achieves $O(L \log L)$ in time complexity and memory usage, and has comparable performance on sequences' dependency alignment. (ii) the self-attention distilling highlights dominating attention by halving cascading layer input, and efficiently handles extreme long input sequences. (iii) the generative style decoder, while conceptually simple, predicts the long time-series sequences at one forward operation rather than a step-by-step way, which drastically improves the inference speed of long-sequence predictions. Extensive experiments on four large-scale datasets demonstrate that Informer significantly outperforms existing methods and provides a new solution to the LSTF problem.Comment: 8 pages (main), 5 pages (appendix) and to be appeared in AAAI202

CD151 Drives Cancer Progression Depending on Integrin α3β1 through EGFR Signaling in Non-Small Cell Lung Cancer

Background Tetraspanins CD151, a transmembrane 4 superfamily protein, has been identified participating in the initiation of a variety of cancers. However, the precise function of CD151 in non-small cell lung cancer (NSCLC) remains unclear. Here, we addressed the pro-tumoral role of CD151 in NSCLC by targeting EGFR/ErbB2 which favors tumor proliferation, migration and invasion. Methods First, the mRNA expression levels of CD151 in NSCLC tissues and cell lines were measured by RT-PCR. Meanwhile, CD151 and its associated proteins were analyzed by western blotting. The expression levels of CD151 in NSCLC samples and its paired adjacent lung tissues were then verified by Immunohistochemistry. The protein interactions are evaluated by co-immunoprecipitation. Flow cytometry was applied to cell cycle analysis. CCK-8, EdU Incorporation, and clonogenic assays were used to analyze cell viability. Wound healing, transwell migration, and matrigel invasion assays were utilized to assess the motility of tumor cells. To investigate the role of CD151 in vivo, lung carcinoma xenograft mouse model was applied. Results High CD151 expression was identified in NSCLC tissues and cell lines, and its high expression was significantly associated with poor prognosis of NSCLC patients. Further, knockdown of CD151 in vitro inhibited tumor proliferation, migration, and invasion. Besides, inoculation of nude mice with CD151-overexpressing tumor cells exhibited substantial tumor proliferation compared to that in control mice which inoculated with vector-transfected tumor cells. Noteworthy, we found that overexpression of CD151 conferred cell migration and invasion by interacting with integrins. We next sought to demonstrate that CD151 regulated downstream signaling pathways via activation of EGFR/ErbB2 in NSCLC cells. Therefore, we infer that CD151 probably affects the sensitivity of NSCLC in response to anti-cancer drugs. Conclusions Based on these results, we demonstrated a new mechanism of CD151-mediated tumor progression by targeting EGFR/ErbB2 signaling pathway, by which CD151 promotes NSCLC proliferation, migration, and invasion, which may considered as a potential target of NSCLC treatment

Advanced NSCLC Patients With EGFR T790M Harboring TP53 R273C or KRAS G12V Cannot Benefit From Osimertinib Based on a Clinical Multicentre Study by Tissue and Liquid Biopsy

BackgroundNon-small cell lung cancer (NSCLC) patients treated with first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) almost always acquire resistance, and the development of novel techniques analyzing circulating tumor DNA (ctDNA) have made it possible for liquid biopsy to detect genetic alterations from limited amount of DNA with less invasiveness. While a large amount of patients with EGFR exon 21 p.Thr790 Met (T790M) benefited from osimertinib treatment, acquired resistance to osimertinb has subsequently become a growing challenge.MethodsWe performed tissue and liquid rebiopsy on 50 patients with EGFR-mutant NSCLC who acquired resistance to first-generation EGFR-TKIs. Plasma samples underwent droplet digital PCR (ddPCR) and next-generation sequencing (NGS) examinations. Corresponding tissue samples underwent NGS and Cobas® EGFR Mutation Test v2 (Cobas) examinations.ResultsOf the 50 patients evaluated, the mutation detection rates of liquid biopsy group and tissue biopsy group demonstrated no significant differences (41/48, 85.4% vs. 44/48, 91.7%; OR=0.53, 95% CI=0.15 to 1.95). Overall concordance, defined as the proportion of patients for whom at least one identical genomic alteration was identified in both tissue and plasma, was 78.3% (36/46, 95% CI=0.39 to 2.69). Moreover, our results showed that almost half of the patients (46%, 23/50) resistant to first-generation EGFR-TKI harbored p.Thr790 Met (T790M) mutation. 82.6% (19/23) of the T790M positive patients were analyzed by liquid biopsy and 60.9% (14/23) by tumor tissue sequencing. Meanwhile, a wide range of uncommon mutations was detected, and novel mechanisms of osimertinib resistance were discovered. In addition, 16.7% (2/12) of the T790M positive patients with either TP53 R237C or KRAS G12V failed to benefit from the subsequent osimertinib treatment.ConclusionOur results emphasized that liquid biopsy is applicable to analyze the drug resistance mechanisms of NSCLC patients treated with EGFR-TKIs. Moreover, we discovered two uncommon mutations, TP53 R273C and KRAS G12V, which attenuates the effectiveness of osimertinib

Table_1_Microbial succession and its effect on the formation of umami peptides during sufu fermentation.DOCX

Sufu, a traditional Chinese fermented food, is famous for its unique flavor, especially umami. However, the formation mechanism of its umami peptides is still unclear. Here, we investigated the dynamic change of both umami peptides and microbial communities during sufu production. Based on peptidomic analysis, 9081 key differential peptides were identified, which mainly involved in amino acid transport and metabolism, peptidase activity and hydrolase activity. Twenty-six high-quality umami peptides with ascending trend were recognized by machine learning methods and Fuzzy c-means clustering. Then, through correlation analysis, five bacterial species (Enterococcus italicus, Leuconostoc citreum, L. mesenteroides, L. pseudomesenteroides, Tetragenococcus halophilus) and two fungi species (Cladosporium colombiae, Hannaella oryzae) were identified to be the core functional microorganisms for umami peptides formation. Functional annotation of five lactic acid bacteria indicated their important functions to be carbohydrate metabolism, amino acid metabolism and nucleotide metabolism, which proved their umami peptides production ability. Overall, our results enhanced the understanding of microbial communities and the formation mechanism of umami peptides in sufu, providing novel insights for quality control and flavor improvement of tofu products.</p

Integrated meta-omics approaches reveal Saccharopolyspora as the core functional genus in huangjiu fermentations.

Identification of the core functional microorganisms in food fermentations is necessary to understand the ecological and functional processes for making those foods. Wheat qu, which provides liquefaction and saccharifying power, and affects the flavor quality, is a key ingredient in ancient alcoholic huangjiu fermentation, while core microbiota of them still remains indistinct. In this study, metagenomics, metabolomics, microbial isolation and co-fermentation were used to investigate huangjiu. Although Aspergillus is usually regarded as core microorganism in wheat qu to initiate huangjiu fermentations, our metagenomic analysis showed that bacteria Saccharopolyspora are predominant in wheat qu and responsible for breakdown of starch and cellulose. Metabolic network and correlation analysis showed that Saccharopolyspora rectivirgula, Saccharopolyspora erythraea, and Saccharopolyspora hirsuta made the greatest contributions to huangjius metabolites, consisting of alcohols (phenylethanol, isoamylol and isobutanol), esters, amino acids (Pro, Arg, Glu and Ala) and organic acids (lactate, tartrate, acetate and citrate). S. hirsuta J2 isolated from wheat qu had the highest amylase, glucoamylase and protease activities. Co-fermentations of S. hirsuta J2 with S. cerevisiae HJ resulted in a higher fermentation rate and alcohol content, and huangjiu flavors were more similar to that of traditional huangjiu compared to co-fermentations of Aspergillus or Lactiplantibacillus with S. cerevisiae HJ. Genome of S. hirsuta J2 contained genes encoding biogenic amine degradation enzymes. By S. hirsuta J2 inoculation, biogenic amine content was reduced by 45%, 43% and 62% in huangjiu, sausage and soy sauce, respectively. These findings show the utility of Saccharopolyspora as a key functional organism in fermented food products

Integrated meta-omics approaches reveal Saccharopolyspora as the core functional genus in huangjiu fermentations

Abstract Identification of the core functional microorganisms in food fermentations is necessary to understand the ecological and functional processes for making those foods. Wheat qu, which provides liquefaction and saccharifying power, and affects the flavor quality, is a key ingredient in ancient alcoholic huangjiu fermentation, while core microbiota of them still remains indistinct. In this study, metagenomics, metabolomics, microbial isolation and co-fermentation were used to investigate huangjiu. Although Aspergillus is usually regarded as core microorganism in wheat qu to initiate huangjiu fermentations, our metagenomic analysis showed that bacteria Saccharopolyspora are predominant in wheat qu and responsible for breakdown of starch and cellulose. Metabolic network and correlation analysis showed that Saccharopolyspora rectivirgula, Saccharopolyspora erythraea, and Saccharopolyspora hirsuta made the greatest contributions to huangjiu’s metabolites, consisting of alcohols (phenylethanol, isoamylol and isobutanol), esters, amino acids (Pro, Arg, Glu and Ala) and organic acids (lactate, tartrate, acetate and citrate). S. hirsuta J2 isolated from wheat qu had the highest amylase, glucoamylase and protease activities. Co-fermentations of S. hirsuta J2 with S. cerevisiae HJ resulted in a higher fermentation rate and alcohol content, and huangjiu flavors were more similar to that of traditional huangjiu compared to co-fermentations of Aspergillus or Lactiplantibacillus with S. cerevisiae HJ. Genome of S. hirsuta J2 contained genes encoding biogenic amine degradation enzymes. By S. hirsuta J2 inoculation, biogenic amine content was reduced by 45%, 43% and 62% in huangjiu, sausage and soy sauce, respectively. These findings show the utility of Saccharopolyspora as a key functional organism in fermented food products

Clinical characteristics of airway impairment assessed by impulse oscillometry in patients with chronic obstructive pulmonary disease: findings from the ECOPD study in China

Abstract Background The role of airway impairment assessed by impulse oscillometry (IOS) in patients with chronic obstructive pulmonary disease (COPD) remains unclear. Therefore, this study aimed to analyze the proportion and clinical characteristics of airway impairment assessed by IOS across COPD severities, and explore whether airway impairment is a subtype of COPD. Methods This study was based on cross-sectional data from the ECOPD cohort in Guangdong, China. Subjects were consecutively recruited from July 2019 to August 2021. They filled out questionnaires and underwent lung function tests, IOS and computed tomography (CT). COPD was defined as post-bronchodilator forced expiratory volume in one second/forced vital capacity  upper limit of normal or < LLN. On the one hand, Poisson regression was employed to analyze the associations between acute exacerbations of COPD (AECOPD) in the previous year and airway impairment. On the other hand, logistic regression was used to assess differences in CT imaging between patients with IOS parameters’ abnormalities and patients with normal IOS parameters. Results 768 COPD subjects were finally enrolled in the study. The proportion of airway impairment assessed by R5, R20, R5–R20, X5, AX, and Fres was 59.8%, 29.7%, 62.5%, 52.9%, 60.9% and 67.3%, respectively. Airway impairment assessed by IOS parameters (R5, R5–R20, X5, AX, and Fres) in patients with COPD was present across all severities of COPD, particularly in GOLD 3–4 patients. Compared with patients with normal IOS parameters, patients with IOS parameters’ abnormalities had more respiratory symptoms, more severe airway obstruction and imaging structural abnormalities. Patients with IOS parameters’ abnormalities assessed by R5 [risk ratio (RR): 1.58, 95% confidential interval (CI): 1.13–2.19, P = 0.007], R5–R20 [RR: 1.73, 95%CI: 1.22–2.45, P = 0.002], X5 [RR: 2.11, 95%CI: 1.51–2.95, P < 0.001], AX [RR: 2.20, 95%CI: 1.53–3.16, P < 0.001], and Fres [RR: 2.13, 95%CI: 1.44–3.15, P < 0.001] had a higher risk of AECOPD in the previous year than patients with normal IOS parameters. Conclusions Airway impairment assessed by IOS may be a subtype of COPD. Future studies are warranted to identify the underlying mechanisms and longitudinal progression of airway impairment

Characteristics of inflammatory phenotypes in patients with chronic obstructive pulmonary disease: a cross-sectional study

Background The relationship between airway inflammation in chronic obstructive pulmonary disease (COPD) and clinical characteristics remains unclear. This study aimed to investigate the airway inflammatory phenotypes in COPD and their association with clinical characteristics.Methods 895 patients with COPD were recruited from Guangdong Province, China in this study. Each patient underwent questionnaire interviews, spirometry testing, CT scans and induced sputum examination. Classification of airway inflammation phenotypes was based on sputum inflammatory cell counts. Covariance analysis was applied to assess associations with airway inflammation phenotypes.Results In this study, we found that neutrophilic phenotype (NP, 58.0%) was the most common airway inflammation phenotype in patients with COPD, followed by mixed granulocytic phenotype (MGP, 32.6%), eosinophilic phenotype (EP, 5.4%) and paucigranulocytic phenotype (PP, 4.0%). Compared with NP patients, those with MGP exhibited more frequent chronic respiratory symptoms, and a higher proportion of individuals classified under Global Initiative for Chronic Obstructive Lung Disease stages 3 and 4. After adjusting for confounding factors, MGP patients had lower lung function, and more severe emphysema and air trapping. On the contrary, patients with PP had the best pulmonary function and less emphysema and air trapping.Conclusions NP was the most common airway inflammation phenotype in patients with COPD. Patients with MGP had more respiratory symptoms, greater loss of lung function, and more severe emphysema and gas trapping compared with those with NP. Meanwhile, PP may be a phenotype of mild damage to lung structure in patients with COPD