New simplified design methods for engineering barriers around contaminated sites with Cauchy boundaries.

Since the 1980s, low-permeability slurry trench cutoff walls have been widely constructed as barriers to retard the migration of contaminants. The thickness of the cutoff walls is a key determinant of the wall service life. Through a series of theoretical derivations, simplified methods for determining the flux limit and concentration limit were proposed to determine the thickness of cutoff walls for contaminated sites with constant pollutant flux. The relative errors of both the flux-based and concentration-based methods increase as the breakthrough criterion of the ratio between the specified limit concentration of the contaminant to the source concentration (C*) and the ratio of the limited value of contaminant flux to the constant source flux (F*) increases, with a given Peclet number PL. The maximum relative error reaches 4% and 6% when C* and F* are both 0.1, which covers most practical situations in cutoff wall design. Good agreements of wall thickness were obtained between the proposed simplified methods and analytical solutions via a clear example. The proposed method can efficiently simplify the design process of cutoff walls with high accuracy, providing a basis for containing contaminated sites.

One-step synthesis of hydroxyl-functionalized ionic hyper-cross-linked polymers with high surface areas for efficient CO2 capture and fixation.

Ionic liquid-based functional materials have attracted significant attention for their distinctive structure in the field of CO2 capture and conversion. In this work, a series of hydroxyl-functionalized ionic hyper-cross-linked polymers are prepared through a one-step Friedel-Crafts reaction involving hypoxanthine (HX) and benzimidazole (BI) as the monomers, along with various halohydrocarbon crosslinking agents. These polymers demonstrate a high specific surface area (558-1480 m2·g-1), well-developed microporous structure, and unique ion sites, enabling them to exhibit remarkable and reversible CO2 adsorption properties. Particularly noteworthy is their CO2 adsorption capacity, which surpasses that of similar ionic polymers documented in the literature, reaching 157.5 mg·g-1 at 273 K and 1 bar. Additionally, these polymers function as recyclable catalysts in the cycloaddition reaction of CO2 and epoxides, enabling the conversion of CO2 into cyclic carbonates with yields of up to 99 % even without a co-catalyst. Mechanism investigation reveals that the introduction of hydroxyl groups in the polymer is the key to improving catalytic activity through a synergistic catalytic effect. This research provides a novel concept for designing ionic functional materials with capabilities in both CO2 adsorption and catalytic activity.

Milk proteomic analysis reveals differentially expressed proteins in high-yielding and low-yielding Guanzhong dairy goats at peak lactation.

The aim of this experiment was to investigate the differential proteomic characteristics of milk from high- and low-yielding Guanzhong dairy goats during the peak lactation period under the same feeding conditions. Nine Guanzhong dairy goats with high yield (H: 3.5 ± 0.17 kg/d) and nine with low yield (L:1.2 ± 0.25 kg/d) were selected for milk proteomic analysis using tandem mass tag technology. A total of 78 differentially expressed proteins were identified. Compared with L, 50 proteins including HK3, HSPB1 and ANXA2 were significantly upregulated in H milk, while 28 proteins including LALBA and XDH were significantly downregulated. Bioinformatics analysis of the differentially expressed proteins showed that galactose metabolism, purine metabolism, glycolysis/gluconeogenesis, MAPK signaling pathway, regulation of actin cytoskeleton and other pathways were closely related to milk yield. HK3, HSPB1, ANXA2, LALBA and XDH were important candidate proteins associated with the milk production characteristics of Guanzhong dairy goats. Our data provide relevant biomarkers and a theoretical basis for improving milk production in Guanzhong dairy goats.

STK214947, a novel indole alkaloids, inhibits HeLa and SK-HEP-1 cells survival and EMT process by blocking the Notch3 and Akt signals.

Apoptosis and epithelial-to-mesenchymal transition (EMT) are closely associated with tumor survival and metastasis. These are the basic events in tumor occurrence and progression. STK214947 is an indole alkaloid with a skeleton that is similar to that of indirubin. Indole alkaloids have attracted considerable attention because of their antitumor activity. However, the relationship between STK214947 and these basic events remains unknown. In this study, the effects of STK214947 on inducing apoptosis and reversing the EMT process in tumor cells were confirmed. Mild concentrations of STK214947 inhibited tumor cell migration by reversing EMT and significantly regulated the expression of EMT-related proteins, including Notch3, E-cadherin, N-cadherin and vimentin. In addition, STK214947 in high concentration could induce apoptosis by down-regulating Notch3, p-Akt/Akt, and NF-κB, and upregulating Caspase 3. These findings support the further development of STK214947 as a potential antitumor small molecule that targets Notch3 and Akt signal transduction in cancer.

X chromosome-wide association study of quantitative biomarkers from the Alzheimer's Disease Neuroimaging Initiative study.

Introduction: Alzheimer's disease (AD) is a complex neurodegenerative disease with high heritability. Compared to autosomes, a higher proportion of disorder-associated genes on X chromosome are expressed in the brain. However, only a few studies focused on the identification of the susceptibility loci for AD on X chromosome. Methods: Using the data from the Alzheimer's Disease Neuroimaging Initiative Study, we conducted an X chromosome-wide association study between 16 AD quantitative biomarkers and 19,692 single nucleotide polymorphisms (SNPs) based on both the cross-sectional and longitudinal studies. Results: We identified 15 SNPs statistically significantly associated with different quantitative biomarkers of the AD. For the cross-sectional study, six SNPs (rs5927116, rs4596772, rs5929538, rs2213488, rs5920524, and rs5945306) are located in or near to six genes DMD, TBX22, LOC101928437, TENM1, SPANXN1, and ZFP92, which have been reported to be associated with schizophrenia or neuropsychiatric diseases in literature. For the longitudinal study, four SNPs (rs4829868, rs5931111, rs6540385, and rs763320) are included in or near to two genes RAC1P4 and AFF2, which have been demonstrated to be associated with brain development or intellectual disability in literature, while the functional annotations of other five novel SNPs (rs12157031, rs428303, rs5953487, rs10284107, and rs5955016) have not been found. Discussion: 15 SNPs were found statistically significantly associated with the quantitative biomarkers of the AD. Follow-up study in molecular genetics is needed to verify whether they are indeed related to AD. The findings in this article expand our understanding of the role of the X chromosome in exploring disease susceptibility, introduce new insights into the molecular genetics behind the AD, and may provide a mechanistic clue to further AD-related studies.

KI-Catalyzed C(sp3)-H Amination and Acyloxylation of Indolin-3-ones Using Air as the Oxidant.

We have developed an efficient and green strategy for the synthesis of C2-amino indolin-3-ones and C2-acyloxy indolin-3-ones via KI-catalyzed C(sp3)-H amination and acyloxylation of indolin-3-ones using air as the oxidant. The reaction provides straightforward access to 2-substituted indolin-3-ones by the direct functionalization of indolin-3-ones at the C2 position under mild conditions. Moreover, the conditions enable direct functionalization of a range of complex pharmaceuticals, providing attractive products for medicinal chemistry programs.

Comparative analysis of different metabolites in semen of Guanzhong dairy goats with different motility rates.

In order to explore the different metabolites of buck semen with different motility stored at 4 °C, the semen of bucks was collected by artificial vagina. The collected semen was divided into high motility group and low motility group after treatment, with 6 replicates set for each group. The semen metabolites of high motility group and low motility group were detected by Liquid Chromatography-Mass Spectrometry (LC-MS). The results showed that 101 different metabolites were detected in the high and low motility groups of bucks, of which 48 metabolites were significantly up-regulated (P < 0.05) and 53 metabolites were significantly down regulated (P < 0.05). Most of these metabolites belonged to lipids and lipid-like molecules, organic acids and their derivatives, and organic oxygen compounds, which were mainly related to energy metabolism. According to the functional enrichment analysis of the former differential metabolites in KEGG database, the top 20 most representative metabolic pathways were detected, among which the glycerophospholipid metabolic pathways changed significantly. From the perspective of metabolomics, this study revealed the differences of metabolites and characteristic compounds of semen with different motility of bucks under low temperature preservation, which provided a scientific basis for the preservation and utilization of semen of Guanzhong dairy goats in the future.

Health-related quality of life among patients with knee osteoarthritis in Guangzhou, China: a multicenter cross-sectional study.

PURPOSES: To investigate health-related quality of life (HRQoL) of patients with knee osteoarthritis (KOA) in Guangzhou, China, and examine its association with selected sociodemographic characteristics as well as knee function. METHODS: This multicenter cross-sectional study included 519 patients with KOA in Guangzhou from April 1 to December 30, 2019. Data on sociodemographic characteristics were obtained using the General Information Questionnaire. The disability was measured using the KOOS-PS, resting pain using the Pain-VAS, and HRQoL using the EQ-5D-5L. The association of selected sociodemographic factors, KOOS-PS and Pain-VAS scores with HRQoL (EQ-5D-5L utility and EQ-VAS scores) were analyzed using linear regression analyses. RESULTS: The median (interquartile range [IQR]) of EQ-5D-5L utility and EQ-VAS scores were 0.744 (0.571-0.841) and 70 (60-80) respectively, lower than the average HRQoL in the general population. Only 3.661% of KOA patients reported no problems in all EQ-5D-5L dimensions, with Pain/Discomfort being the most frequently affected dimension (78.805%). The correlation analysis showed that the KOOS-PS score, Pain-VAS score and HRQoL were moderately or strongly correlated. Patients with cardiovascular disease, no daily exercise, and high KOOS-PS or Pain-VAS scores had lower EQ-5D-5L utility scores; and patients with body mass index (BMI) > 28 ,high KOOS-PS or Pain-VAS scores had lower EQ-VAS scores. CONCLUSIONS: Patients with KOA had relatively low HRQoL. Various sociodemographic characteristics as well as knee function were associated with HRQoL in regression analyses. Providing social support and improving their knee function through methods such as total knee arthroplasty might be crucial to improve their HRQoL.

Basic constituents, bioactive compounds and health-promoting benefits of wine skin pomace: A comprehensive review.

Wine pomace (WP) is a major byproduct generated during winemaking, and skin pomace (SKP) comprises one of the most valuable components of WP. Since SKP differs in composition and properties from seed pomace (SDP), precise knowledge of SKP will aid the wine industry in the development of novel, high-value products. The current review summarizes recent advances in research relating to SKP presents a comprehensive description of the generation, composition, and bioactive components, primarily focusing on the biological activities of SKP, including antioxidant, gastrointestinal health promotion, antibacterial, anti-inflammatory, anticancer, and metabolic disease alleviation properties. Currently, the separation and recovery of skins and seeds is an important trend in the wine industry for the disposal of winemaking byproducts. In comparison to SDP, SKP is rich in polyphenols including anthocyanins, flavonols, phenolic acids, stilbenes, and some proanthocyanidins, as well as dietary fiber (DF). These distinctive benefits afford SKP the opportunity for further development and application. Accordingly, the health-promoting mechanism and appropriate application of SKP will be further elucidated in terms of physiological activity, with the progress of biochemical technology and the deepening of related research.

An Efficient Bayesian Method for Estimating the Degree of the Skewness of X Chromosome Inactivation Based on the Mixture of General Pedigrees and Unrelated Females.

Skewed X chromosome inactivation (XCI-S) has been reported to be associated with some X-linked diseases. Several methods have been proposed to estimate the degree of XCI-S (denoted as γ) for quantitative and qualitative traits based on unrelated females. However, there is no method available for estimating γ based on general pedigrees. Therefore, in this paper, we propose a Bayesian method to obtain the point estimate and the credible interval of γ based on the mixture of general pedigrees and unrelated females (called mixed data for brevity), which is also suitable for only general pedigrees. We consider the truncated normal prior and the uniform prior for γ. Further, we apply the eigenvalue decomposition and Cholesky decomposition to our proposed methods to accelerate the computation speed. We conduct extensive simulation studies to compare the performances of our proposed methods and two existing Bayesian methods which are only applicable to unrelated females. The simulation results show that the incorporation of general pedigrees can improve the efficiency of the point estimation and the precision and the accuracy of the interval estimation of γ. Finally, we apply the proposed methods to the Minnesota Center for Twin and Family Research data for their practical use.

Study on comparative analysis of differential metabolites in Guanzhong dairy goat semen before and after freezing.

In order to explore the differential metabolites between fresh and frozen-thawed semen of Guanzhong dairy goats, semen samples were collected by artificial vagina method, and divided into fresh and frozen-thawed semen groups, with six replicates in each group. Liquid Chromatography-mass spectrometry (LC-MS) technology was used to detect semen metabolites in both groups. The metabolites were analyzed and identified by the combination of multidimensional statistical analysis, namely principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), orthogonal partial least squares discriminant analysis (OPLS-DA) and univariate statistical analysis, Differential metabolites were identified according to One-step Solution for Identification of Small Molecules in Metabolomics Studies (OSI/SMMS) combined with Human Metabolome Database (HMDB), Lipidmaps and Metlin and the metabolic pathways of different metabolites were enriched and analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The results showed that a total of 53 differential metabolites were detected in fresh and frozen-thawed semen groups, of which 10 metabolites were significantly up-regulated (P < 0.05) and 43 were significantly down-regulated (P < 0.05). Most of the metabolites belonged to lipids and lipid-like molecules, organic acids and their derivatives, organic oxygen compounds, etc. According to the functional enrichment analysis of the top twenty differential metabolites in the KEGG database, significant changes occurred in linoleic acid metabolism pathway out of total eleven pathways observed. These differential metabolites can be used as metabolic markers of sperm cryo-injury in dairy goats.

Dance activity interventions targeting cognitive functioning in older adults with mild cognitive impairment: A meta-analysis.

Objectives: To comprehensively determine the effect of dance activities on the cognitive functions and its sub-domains of older adults with mild cognitive impairment (MCI). Methods: We obtained data from PubMed, Web of Science, EBSCO, China national knowledge infrastructure, Wanfang data, and VIP databases from 2017/01/01 to 2022/03/01. We included trials of older adults with MCI that underwent dance activity intervention and fulfilled the inclusion criteria. Two researchers independently assessed the quality of the study using the Cochrane risk of the bias assessment tool. Meta-analysis was performed when data were available, with further subgroup analysis, using Review Manager 5.4, and sensitivity analysis was performed using Stata software 15.1. Results: Search terms yielded 183 articles, of which 12 fulfilled the inclusion criteria. This included 7 high-quality studies and 5 medium-quality studies. A total of 820 older adults were analyzed. Results showed that dance activity had beneficial effects for global cognition [SMDMMSE = 0.65, 95% CIMMSE (0.20, 1.09), p MMSE = 0.004; SMDMoCA = 0.87, 95% CIMoCA (0.44, 1.29), p MoCA < 0.0001], memory [SMD = 0.61, 95% CI (0.35, 0.88), p < 0.00001], visuospatial function [SMD = -0.39, 95% CI (-0.60, -0.19), p = 0.0002], cognitive flexibility [SMD = -0.31, 95% CI (-0.52, -0.11), p = 0.003], attention [SMD = 0.34, 95% CI (0.07, 0.61), p = 0.01], and balance [SMD = 1.25, 95% CI (0.06, 2.44), p = 0.04]. Further subgroup analysis showed that open-skill dance activity (OSDA) was more effective in promoting global cognition in older adults with MCI than closed-skill dance activity (CSDA) because of the different stimulation provided by the two types of dance activities in the brain regions of the older adults (p = 0.0002). It could be speculated that dance activity improved cognitive function mainly by affecting the microstructure and function of the cingulate tract, hippocampus, cardiovascular function, and other brain areas of older adults with MCI. Conclusion: Dance activities can significantly improve global cognition, memory, visuospatial function, cognitive flexibility, attention, and balance in older adults with MCI. However, more trials with rigorous study designs are necessary to provide more concrete evidence in the future.

The effect of aggressive management of intraoperative body temperature on postoperative APACHE II score and prognosis in high-risk patients undergoing thoracoscopic surgery.

Background: Intraoperative hypothermia is related with postoperative complication, longer length of stay (LoS) and mortality. Acute Physiology and Chronic Health Evaluation II (APACHE II) it the most commonly used evaluation system for assessing the severity and clinical prognosis of patients. This study sought to examine the effect of intraoperative body temperature on postoperative APACHE II scores and the prognosis of high-risk patients undergoing thoracoscopic surgery. Methods: This study used the clinical data of patients from a multicenter randomized controlled trial who had undergone thoracoscopic surgery at our center (NCT03111875). In our center were randomly assigned (1:1) to receive either aggressive warming to a target core temperature of 37 ℃ or routine thermal management to a target of 35.5 ℃ during non-cardiac surgery. Randomisation was computer-generated. Eligible patients (aged ≥45 years) had at least one cardiovascular risk factor, were scheduled for inpatient noncardiac surgery expected to last 2-6 h with general anaesthesia. We retrieved medical information through the electronic medical record system. The primary outcome was the postoperative APACHE II scores, APACHE II score variation. The secondary outcome was Quality of Recovery-15 (QoR-15) scores, LoS in hospital, postoperative complications, infections, and deaths of the patients were recorded, and a logistic regression analysis was conducted to stratify the risk factors for the APACHE II score. Results: Group R comprised 121 patients and Group A comprised 84 patients. Group A had lower postoperative APACHE II scores (P=0.046) and a lower probability of a grade increase than Group R (P=0.005). However, no significant differences were found in terms of the QoR-15 scores, LoS, postoperative complications, infections, and deaths between the 2 groups. The logistic regression showed that aggressive warming, age, and the American Society of Anesthesiologists (ASA) grade were risk factors for the deterioration of postoperative APACHE II scores. Conclusions: The active adoption of various passive and aggressive warming strategies to keep the core body temperature ≥37 ℃ during thoracoscopic surgery significantly reduced increases in APACHE II scores, which is different from age and ASA grade, and was the only intervention factor.

Effect of hypotension prediction index in the prevention of intraoperative hypotension during noncardiac surgery: A systematic review.

Intraoperative hypotension (IOH) is common in noncardiac surgery and is associated with serious postoperative complications. Hypotension Prediction Index (HPI) has shown high sensitivity and specificity for predicting hypotension and may reduce IOH in noncardiac surgery. We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the applications and effects of HPI in reducing hypotension during noncardiac surgery. We comprehensively searched the PubMed, Embase, Cochrane Library, Google Scholar, and http://ClinicalTrials.gov databases to identify RCTs conducted before May 2022. The primary outcome measures were the time-weighted average (TWA) of hypotension and the area under the hypotensive threshold (65 mmHg). Secondary outcomes were the incidence and duration of hypotension and the percentage of hypotensive time during surgery. The Cochrane Risk of Bias (RoB) tool was used to assess the quality of selected studies. We conducted data synthesis for median differences and assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We included five studies with a total of 461 patients. Limited evidence suggested that HPI-guided intraoperative hemodynamics management leads to lower a) TWA of hypotension (median of difference of medians [MDM], -0.27 mmHg; 95% confidence interval [CI], -0.38, -0.01), b) area under the hypotensive threshold (MDM, -60.28 mmHg*min; 95% CI, -74.00, -1.30), c) incidence of hypotension (MDM, -4.50; 95% CI, -5.00, -4.00), d) total duration of hypotension (MDM, -12.80 min; 95% CI, -16.11, -3.39), and e) percentage of hypotension (MDM, -5.80; 95% CI, -6.65, -4.82) than routine hemodynamic management during noncardiac surgery. However, only very low- to low-quality evidence on the benefit of intraoperative HPI-based hemodynamic management is available. Our review revealed that HPI has the potential to reduce the occurrence, duration, and severity of IOH during noncardiac surgery compared to standard intraoperative care with proper adherence to the protocol. Systematic review registration PROSPERO CRD42022333834.

Robust association tests for quantitative traits on the X chromosome.

The genome-wide association study is an elementary tool to assess the genetic contribution to complex human traits. However, such association tests are mainly proposed for autosomes, and less attention has been given to methods for identifying loci on the X chromosome due to their distinct biological features. In addition, the existing association tests for quantitative traits on the X chromosome either fail to incorporate the information of males or only detect variance heterogeneity. Therefore, we propose four novel methods, which are denoted as QXcat, QZmax, QMVXcat and QMVZmax. When using these methods, it is assumed that the risk alleles for females and males are the same and that the locus being studied satisfies the generalized genetic model for females. The first two methods are based on comparing the means of the trait value across different genotypes, while the latter two methods test for the difference of both means and variances. All four methods effectively incorporate the information of X chromosome inactivation. Simulation studies demonstrate that the proposed methods control the type I error rates well. Under the simulated scenarios, the proposed methods are generally more powerful than the existing methods. We also apply our proposed methods to data from the Minnesota Center for Twin and Family Research and find 10 single nucleotide polymorphisms that are statistically significantly associated with at least two traits at the significance level of 1 × 10-3.

Comparative functional analysis of malate metabolism genes in Oenococcus oeni and Lactiplantibacillus plantarum at low pH and their roles in acid stress response.

Oenococcus oeni and Lactiplantibacillus plantarum are major wine-associated lactic acid bacteria that positively influence wine by carrying out malolactic fermentation. O. oeni is the most widely used commercial starter in winemaking because of its fast and efficient malate metabolism capacity under harsh wine conditions. To date, very little is known about the specific molecular mechanism underlying the differences in malate metabolism between O. oeni and L. plantarum under harsh wine conditions. Therefore, in this study, the functions of genes encoding malic enzyme (ME) and malolactic enzyme (MLE) under acid stress in O. oeni and L. plantarum, previously described to have the ability to direct malate metabolism, were comparatively verified through genetic manipulation in L. plantarum. Results showed that the MLE was the only enzyme responsible for direct malate metabolism under acid stress in O. oeni and L. plantarum. In addition, the MLEs in O. oeni and L. plantarum were positively related to acid tolerance by metabolizing malate and increasing the medium pH. Furthermore, the MLE in O. oeni exhibited significantly higher malate metabolism activity than that in L. plantarum under acid stress.

Detection of Parent-of-Origin Effects for the Variants Associated With Behavioral Disinhibition in the MCTFR Data.

Behavioral disinhibition is one of the important characteristics of many mental diseases. It has been reported in literature that serious behavioral disinhibition will affect people's health and greatly reduce people's quality of life. Meanwhile, behavioral disinhibition can easily lead to illegal drug abuse and violent crimes, etc., which will bring great harm to the society. At present, large-scale genome-wide association analysis has identified many loci associated with behavioral disinhibition. However, these studies have not incorporated the parent-of-origin effects (POE) into analysis, which may ignore or underestimate the genetic effects of loci on behavioral disinhibition. Therefore, in this article, we analyzed the five phenotypes related to behavioral disinhibition in the Minnesota Center for Twin and Family Research data (nicotine, alcohol consumption, alcohol dependence, illicit drugs, and non-substance use related behavioral disinhibition), to further explore the POE of variants on behavioral disinhibition. We applied a linear mixed model to test for the POE at a genome-wide scale on five transformed phenotypes, and found nine SNPs with statistically significant POE at the significance level of 5 × 10-8. Among them, SNPs rs4141854, rs9394515, and rs4711553 have been reported to be associated with two neurological disorders (restless legs syndrome and Tourette's syndrome) which are related to behavioral disinhibition; SNPs rs12960235 and rs715351 have been found to be associated with head and neck squamous cell carcinoma, skin cancer and type I diabetes, while both SNPs have not been identified to be related to behavioral disinhibition in literature; SNPs rs704833, rs6837925, rs1863548, and rs11067062 are novel loci identified in this article, and their function annotations have not been reported in literature. Follow-up study in molecular genetics is needed to verify whether they are surely related to behavioral disinhibition.

Gene-Based Methods for Estimating the Degree of the Skewness of X Chromosome Inactivation.

Skewed X chromosome inactivation (XCI-S) has been reported to be associated with some X-linked diseases, and currently several methods have been proposed to estimate the degree of the XCI-S (denoted as γ) for a single locus. However, no method has been available to estimate γ for genes. Therefore, in this paper, we first propose the point estimate and the penalized point estimate of γ for genes, and then derive its confidence intervals based on the Fieller's and penalized Fieller's methods, respectively. Further, we consider the constraint condition of γ∈[0, 2] and propose the Bayesian methods to obtain the point estimates and the credible intervals of γ, where a truncated normal prior and a uniform prior are respectively used (denoted as GBN and GBU). The simulation results show that the Bayesian methods can avoid the extreme point estimates (0 or 2), the empty sets, the noninformative intervals ([0, 2]) and the discontinuous intervals to occur. GBN performs best in both the point estimation and the interval estimation. Finally, we apply the proposed methods to the Minnesota Center for Twin and Family Research data for their practical use. In summary, in practical applications, we recommend using GBN to estimate γ of genes.

Methionine addition improves the acid tolerance of Lactiplantibacillus plantarum by altering cellular metabolic flux, energy distribution, lipids composition.

This paper reported a wine-derived lactic acid bacterium, Lactiplantibacillus plantarum XJ25, which exhibited higher cell viability under acid stress upon methionine supplementation. Cellular morphology and the composition of the cytomembrane phospholipids revealed a more solid membrane architecture presented in the acid-stressed cells treated with methionine supplementation. Transcriptional analysis showed L. plantarum XJ25 reduced methionine transport and homocysteine biosynthesis under acid stress. Subsequent overexpression assays proved that methionine supplementation could alleviate the cell toxicity from homocysteine accumulation under acid stress. Finally, L. plantarum XJ25 employed energy allocation strategy to response environmental changes by balancing the uptake methionine and adjusting saturated fatty acids (SFAs) in membrane. These data support a novel mechanism of acid resistance involving methionine utilization and cellular energy distribution in LAB and provide crucial theoretical clues for the mechanisms of acid resistance in other bacteria.

Integrative multiomics analysis of the acid stress response of Oenococcus oeni mutants at different growth stages.

BACKGROUND: Acid stress is one of the most important environmental stresses that adversely affect the growth of lactic acid bacteria (LAB), such as Oenococcus oeni which was isolated from grape-berries and mainly used in wine fermentation. The aim of this paper is to comprehensively characterize the mechanisms of acid stress regulation in O. oeni and to provide a viable theoretical basis for breed and improvement of existing LAB. METHOD: First, six O. oeni mutants with acid-sensitive (strains b2, a1, c2) and acid-tolerant (strains b1, a3, c1) phenotypes were screened from three wild-type O. oeni, and then their genome (sequencing), transcriptome and metabolome (LC-MS/MS) were examined. RESULTS: A total of 459 genes were identified with one or more intragenic single nucleotide polymorphisms (SNPs) in these mutants, and were extensively involved in metabolism and cellular functions with a high mutation rates in purine (46%) and pyrimidine (48%) metabolic pathways. There were 210 mutated genes that cause significant changes in expression levels. In addition, 446 differentially accumulated metabolites were detected, and they were consistently detected at relatively high levels in the acid-tolerant O. oeni mutant. The levels of intracellular differentially expressed genes and differential metabolites changed with increasing culture time. CONCLUSION: The integrative pathways analysis showed that the intracellular response associated with acid regulation differed significantly between acid-sensitive and acid-tolerant O. oeni mutants, and also changed at different growth stages.