Acid Changes Research Articles

Ginger Extract Improves Cognitive Dysfunction via Modulation of Gut Microbiota-Derived Short-Chain Fatty Acids in D-Galactose/Ovariectomy-Induced Alzheimer-Like Disease.

Alzheimer's disease (AD) is the most common form of dementia with complex causes and limited treatment options. Recent research has suggested a connection between the progression of AD and the activity of gut microbiota. Ginger, a plant known for its anti-inflammatory, antioxidant, and neuroprotective properties, has gained attention as a potential treatment for alleviating AD symptoms. In this study, we induced an AD model in female rats through ovariectomy and D-galactose injection and then investigated the protective effects of oral administration of ginger ethanolic extract. We assessed changes in short-chain fatty acids (SCFAs), learning and memory abilities, neuroinflammatory markers in plasma, and the hippocampus, as well as histological changes in the intestine and hippocampus in sham-operated, diseased, and treatment groups. Oral administration of ginger ethanolic extract improved gut microbiota activity, increased SCFA levels, and enhanced the expression of tight junction proteins. Additionally, ginger extract reduced the concentrations of TNF-α and IL-1β in both plasma and the hippocampus. Furthermore, it significantly reduced cell death and amyloid plaque deposition in the hippocampal tissue. These physiological changes resulted in improved performance in learning and memory tasks in rats treated with ginger compared with the disease group. These findings provide compelling evidence for the beneficial effects of ginger on the gut-brain axis, leading to improvements in learning and memory through the reduction of neuroinflammation.

RNA editing-induced structural and functional adaptations of NAD9 in Triticum aestivum under drought stress

IntroductionMitochondria are essential organelles in eukaryotic cells, producing ATP through the electron transport chain to supply energy for cellular activities. Beyond energy production, mitochondria play crucial roles in cellular signaling, stress responses, and the regulation of reactive oxygen species. In plants, mitochondria are one of the keys to responding to environmental stresses which can significantly affect crop productivity, particularly in crops like wheat. RNA editing, a post-transcriptional RNA modification process in mitochondria, is linked to regulating these stress responses.MethodsThis study explores RNA editing patterns in the nad9 gene of wheat drought-tolerant (Giza168) and drought-sensitive (Gemmiza10) wheat cultivars under drought stress to understand plant adaptation mechanisms. RNA-seq data for these cultivars were analyzed using CLC Genomic Workbench to identify RNA editing sites in the nad9 gene, examining subsequent amino acid changes and predicting secondary structure modifications. These RNA editing sites were validated using qRT-PCR on drought-treated seedlings at 0, 2, and 12 hours post-treatment. Protein models were generated using AlphaFold, with functional predictions and structure verification conducted using various bioinformatics tools to investigate the effect of RNA editing on protein level.ResultsThe results showed significant RNA editing events, especially C-to-T conversions, in the nad9 gene across different drought exposure times. Giza168 had 22 editing sites, while Gemmiza10 had 19, with several showing significant differences between control and stress conditions. RNA editing influenced the NAD9 protein's secondary structure, particularly beta sheets, and 3D modeling highlighted the structural impacts of these edits. The N-terminal region of NAD9 contained important regulatory motifs, suggesting a complex regulatory environment.DiscussionThis study reveals key editing sites that differ between drought-tolerant and sensitive wheat cultivars, impacting NAD9 protein structures and highlighting the role of RNA editing in enhancing drought resilience. Additionally, the study suggests potential regulatory mechanisms, including phosphorylation and ubiquitination that influence mitochondrial stability and function.

Environmental Drivers of the Divergence of Harveyi Clade Pathogens with Distinctive Virulence Gene Profiles

Fish and shellfish pathogens of the Harveyi clade of the Vibrio genus cause significant losses to aquaculture yields and profits, with some of them also causing infections in humans. The present study aimed to evaluate the presence of Harveyi clade fish and shellfish pathogens and their possible diversification in response to environmental drivers in southeastern USA waters. The presence and abundance of potential pathogens were evaluated via the detection and quantitation of six Harveyi-clade-specific virulence genes (toxR, luxR, srp, vhha, vhh, and vhp; VGs) in environmental DNA with clade-specific primers. The environmental DNA was obtained from water and sediments collected from three Georgia (USA) cultured clam and wild oyster grounds. In sediments, the VG concentrations were, on average, three orders of magnitude higher than those in water. The most and least frequently detected VGs were vhp and toxR, respectively. In water, the VGs split into two groups based on their seasonal trends. The first group, composed of luxR, vhp, vhha, and vhh, peaked in August and remained at lower concentrations throughout the duration of the study. The second group, composed of toxR and srp, peaked in June and disappeared between July and December. The first group revealed a high adaptation of their carriers to an increase in temperature, tolerance to a wide range of pH, and a positive correlation with salinity up to 25 ppt. The second group of VGs demonstrated a lower adaptation of their carriers to temperature and negative correlations with pH, salinity, potential water density, conductivity, and dissolved solids but a positive correlation with turbidity. No such trends were observed in sediments. These data reveal the role of VGs in the adaptability of the Harveyi clade pathogens to environmental parameters, causing their diversification and possibly their stratification into different ecological niches due to changes in water temperature, acidity, salinity, and turbidity. This diversification and stratification may lead to further speciation and the emergence of new pathogens of this clade. Our data urge further monitoring of the presence and diversification of Harveyi clade pathogens in a global warming scenario.

Soil Acidification and Its Temporal Changes in Tea Plantations of Guizhou Province, Southwest China

ABSTRACTSoil acidification is a significant problem in intensive agricultural systems, particularly in tea plantations. Guizhou province, located in the center of the karst mountainous region of southwest China, has the largest tea plantation area in China. However, the soil acidification characteristics in the tea plantations of Guizhou province, as well as their temporal changes, have not yet been adequately studied. Therefore, soil acidification and associated soil properties in the major tea‐planting counties of Guizhou province were extensively assessed, and the temporal changes in soil acidity over the past 11 years were also evaluated through long‐term and short‐term experiments. The results showed that the average soil pH in the tea plantations in Guizhou province varied from 4.08 to 4.87, with a mean of 4.47. The average cation exchange capacity (CEC), TEA (total exchangeable acidity, TEA), EH (exchangeable H+), and EA (exchangeable Al3+) values were 9.6, 3.7, 5.8, and 19.0 cmol/kg, respectively. Seasonal changes in tea plantation soil pH were observed in low‐ and moderately acidic soils but not in highly acidic soils. The soil pH values did not significantly change during three consecutive years of in situ observations but significantly decreased over the past 11 years at an average of 0.03 yearly. Correlation analysis revealed that the soil pH in tea plantations was significantly positively correlated with the content of specific amino acids, such as glutamic acid, arginine, and valine, but was significantly negatively correlated with certain soil physicochemical properties. The findings of this study indicate that soil acidification in tea plantations of the Guizhou province is severe and possesses distinctive attributes that should be considered for its effective management.

Aging delays the suppression of lipolysis and fatty acid oxidation in the postprandial period.

Plasma glycerol and free fatty acid concentrations decrease following oral glucose consumption, but changes in the rate of lipolysis during an oral glucose tolerance test (OGTT) have not been documented in conjunction with changes in fatty acid (FA) oxidation or reesterification rates in healthy individuals. After a 12-h overnight fast, 15 young (21-35 yr; 7 men and 8 women) and 14 older (60-80 yr; 7 men and 7 women) participants had the forearm vein catheterized for primed continuous infusion of [1,1,2,3,3-2H]glycerol. A contralateral hand vein was catheterized for arterialized blood sampling. Indirect calorimetry was performed simultaneously to determine total FA and carbohydrate (CHO) oxidation rates (Rox). Total FA reesterification rates (Rs) were estimated from tracer-measured lipolytic and FA oxidation rates. After a 90-min equilibration period, participants underwent a 120-min, 75-g OGTT. Glycerol rate of appearance (Ra), an index of lipolysis, decreased significantly from baseline 5 min postchallenge in young participants and 30 min in older participants. At 60 min, FA Rox decreased in both groups, but was significantly higher in older participants. Between 5 and 90 min, CHO Rox was significantly lower in older participants. In addition, FA Rs was significantly lower in older participants at 60 and 90 min. The area under the curve (AUC) for FA Rox was greater than that for FA Rs in older, but not in young participants. Our results indicate that, in aging, the postprandial suppression of lipolysis and FA oxidation are delayed such that FA oxidation is favored over CHO oxidation and FA reesterification.NEW & NOTEWORTHY To our knowledge, our investigation is the first to demonstrate changes in lipolysis during an oral glucose tolerance test (OGTT) in healthy young and older individuals. Plasma glycerol and free fatty acid concentrations changed after glycerol rate of appearance (Ra), indicating that plasma concentrations are incomplete surrogates of the lipolytic rate. Moreover, simultaneous determinations of substrate oxidation rates are interpreted to indicate that metabolic inflexibility in aging is characterized by delayed changes in postprandial substrate utilization related to the lipolytic rate.

A Distinct Genotype, D/Ep6, Detected in Korean Female Patients: Chlamydia trachomatis Characterization from 2017 - 2018.

The objective of this study lies in identifying the dominant genotype of C. trachomatis isolated in Republic of Korea (ROK) between 2017 and 2018. A total of 504 clinical cervicovaginal swabs from patients were collected and inoculated on McCoy cell monolayers to isolate Chlamydial agents. C. trachomatis isolates were analyzed by sequencing of its ompA gene. A total of 54 C. trachomatis isolates were obtained. The constructed phylogenetic tree revealed the genotypes of isolates are D/Ep6 (48, 88.89%), D/Ep6-like (5, 9.26%), and Ja (1, 1.85%). The C. trachomatis D/Ep6-like have one single nucleotide polymorphism (SNP) compared to C. trachomatis D/Ep6, leading to E870K amino acid change. Phylogenetic analysis demonstrated globally rare C. trachomatis D/Ep6 was dominant in the ROK from 2017 to 2018. Findings in this study act as a keystone, bridging past and present molecular epidemiology of C. trachomatis in context of ROK.

A type VI secretion system in Burkholderia species cenocepacia and orbicola triggers distinct macrophage death pathways independent of the pyrin inflammasome.

The Burkholderia cepacia complex contains opportunistic pathogens that cause chronic infections and inflammation in the lungs of people with cystic fibrosis. Two closely related species within this complex are Burkholderia cenocepacia and the recently classified Burkholderia orbicola. B. cenocepacia and B. orbicola encode a type VI secretion system and the effector TecA, which is detected by the pyrin/caspase-1 inflammasome, and triggers macrophage inflammatory death. We previously showed that the pyrin inflammasome was dispensable for lung inflammation in mice infected with B. orbicola AU1054, indicating this species activates an alternative pathway of macrophage inflammatory death. Notably, B. cenocepacia strains J2315 and K56-2 can damage macrophage phagosomes, and K56-2 triggers activation of the caspase-11 inflammasome, which detects cytosolic lipopolysaccharide. Here, we investigated inflammatory cell death in pyrin- (Mefv-/-) or caspase-1/caspase-11- (Casp1/11-/-) deficient mouse macrophages infected with B. cenocepacia J2315 or K56-2 or B. orbicola AU1054 or PC184. Macrophage inflammatory death was measured by cleavage of gasdermin D protein, the release of cytokines IL-1α and IL-1β, and plasma membrane rupture. We found that J2315 and K56-2 are detected by the caspase-11 inflammasome in Mefv-/- macrophages, resulting in IL-1β release. By contrast, inflammasome activation was not detected in Mefv-/- macrophages infected with AU1054 or PC184. Instead, AU1054 triggered an alternative macrophage inflammatory death pathway that required TecA and resulted in plasma membrane rupture and IL-1α release. Structural modeling of TecA orthologs in B. cenocepacia and B. orbicola suggested that amino acid changes in the latter may underlie its ability to trigger a non-inflammasome macrophage death pathway.

Response of One-Carbon Biomarkers in Maternal and Cord Blood to Folic Acid Dose During Pregnancy

Background/Objectives: The folate Recommended Daily Allowance (RDA) for pregnant women is 600 μg/day dietary folate equivalents, which is equivalent to approximately 400 μg folic acid. Many prenatal supplements contain much higher doses of folic acid. The body’s ability to reduce synthetic folic acid to the metabolically active form may be exceeded with high levels of supplementation. The objective of this double-blinded randomized controlled intervention trial was to determine changes in unmetabolized folic acid and other biomarkers of folate and one-carbon metabolism in maternal and cord blood in response to a folic acid dose commonly found in prenatal supplements (800 μg/day) compared to the dose equivalent of the RDA (400 μg/day). Methods: Healthy pregnant women were randomized and provided supplements from their first prenatal visit (<12 weeks gestation) through delivery. Maternal blood was collected at baseline and delivery. Umbilical cord blood from the mothers was collected at delivery. Results: A repeated measures analysis of variance revealed that there was a significant group supplemental dose effect (p = 0.0225) on serum unmetabolized folic acid concentration in mothers but no difference in cord blood unmetabolized folic acid concentrations between groups. Mixed effects analysis found a significant overall effect of pre-pregnancy BMI (p = 0.0360) and length of previous folic acid supplementation (p = 0.0281) on serum folate concentrations. No treatment effect was seen in RBC folate concentrations. Choline concentrations were higher in cord blood from the 800 μg/day group compared to the 400 μg/day group, but there was no group effect in maternal choline concentrations. Conclusions: The results indicate that folic acid dose during pregnancy affects certain folate and one-carbon biomarkers, and these effects are not consistent between maternal and cord blood. Potential long-term effects of these results on both mothers and offspring are unknown and merit further investigation.

Characterization of quality parameters and phytosterol content in oils and their formulated margarines

AbstractUnlike lipid stability and oxidation studies in commonly used edible oils and margarines, margarines formulated with unconventional oils are not well characterized. This study investigated the effect of heat treatment (HT) on the stability and content of phytosterol in njangsa seed oil (NSO), bush mango oil (BMO), soybean oil (SBO), coconut oil (CCO), and margarines formulated from their blends: BN (BMO and NSO), BS (BMO and SBO), CN (CCO and NSO), CS (CCO and SBO), and commercial margarines (CM1 and CM2). Both oils and margarines were heat‐treated at 130, 170, and 210°C for 10, 15, 20, and 120 min (only oils). Changes in free fatty acid (FFA), peroxide value (PV), para‐anisidine value (AnV), and fatty acid (FA) composition and phytosterol content were determined after 20 min (margarines) and 120 min (oils) of HT and compared to their control/pre‐HT/unheated (UH) counterparts. The FA composition did not change significantly with HT. Polyunsaturated fatty acids (PUFA)‐rich oils such as NSO and SBO showed significantly higher increase in FFA content with HT compared with oils with higher saturated fatty acid content (BMO and CCO). Oils with higher proportions of linoleic acid, such as SBO (68.3%) and NSO (60.35%), had higher AnV at the end of the HT compared with oils with lower content, such as BMO (0.51%). Phytosterol content fluctuated with HT, and changes in content were generally more pronounced in β‐sitosterol than in stigmasterol and campesterol. Both principal component analysis (PCA) and partial least‐squares discriminant analysis (PLS‐DA) were carried out to observe possible clusters. The results suggest that changes in quality and content of oils and margarines during heating are dependent on more than their fatty acid composition.

Pharmacogenomics of CRP response to statins: a GIST consortium study

Abstract Introduction Statins are first line treatments in the primary and secondary prevention of cardiovascular disease. Prior clinical studies have shown that statins act independently of lipid lowering mechanisms to decrease C-reactive protein (CRP), a marker of inflammation. Purpose To elucidate genetic loci associated with CRP response to statins. Methods CRP response was specified as the change from baseline in log CRP after at least 4 weeks of statin therapy. Cohort level Genome-wide Association Studies (GWAS) of this CRP response was performed by linear regression analysis adjusted for baseline CRP, age, sex and BMI covariates using genetic data imputed to 1000 Genomes, testing ~10 million single nucleotide polymorphisms (SNPs) of minor allele frequency (MAF) >2%. Following quality control with EasyQC, a meta-analysis was conducted with METAL to combine GWAS results from six different cohorts of European ancestry (CARDS, FHS, JUPITER, MESA, PARC, PROSPER) within the GIST consortium. 1Mb loci regions were defined, centred +/-500kb around the lead SNP. Conditional analysis was performed using GCTA. Results There were 11,075 statin-treated individuals. The meta-analysis results revealed two loci achieving genome wide significance (P<5e-8): APOE (chr 19) and HNF1A (chr 12) (Figure 1). A signal at the CRP locus was highly suggestive (P=2.3e-7). All three loci are known to be associated with CRP levels in the absence of statin. Conditional analysis did not reveal secondary signals. The most associated variant at the APOE locus was the missense SNP rs429358, which contributes to the APOE E4 haplotype and is a risk locus for both dyslipidaemia and Alzheimer’s dementia. It is a C>T missense variant of MAF 0.12 leading to a R/C amino acid change, more common in African ancestry populations (MAF 0.27), and least common in Asian populations (MAF 0.09). A nominally significant association (P=0.09) for interaction with randomized allocation to statin v. placebo within samples derived from clinical trials supports this pharmacogenetic effect at APOE beyond genetic effects on baseline CRP levels. The most associated variant at the HNF1A locus was the intronic SNP rs11065384, which is in strong LD with the HNF1A missense SNP (rs1169288). The HNF1A locus is associated with diabetes, cholesterol levels, and coronary artery disease. There was no between-study heterogeneity at the top three loci (P>0.1), and forest plots show contribution to these signals from all 6 studies within the meta-analysis (Figure 2 A,B,C). Conclusions APOE and HNF1A are associated with CRP response to statins at the level of genome-wide significance. TheAPOE E4 signal is also known to be associated with LDL-Cholesterol response to statins, whereas the HNF1A locus is identified here for the first time as a pharmacogenetic determinant of statin response. The effect of this interindividual variability in CRP response on non-cardiovascular clinical outcomes should be elucidated.Figure 1Figure 2 A,B,C

PIM-1L Kinase Binds to and Inactivates SRPK1: A Biochemical and Molecular Dynamics Study.

SR/RS dipeptide repeats vary in both length and position, and are phosphorylated by SR protein kinases (SRPKs). PIM-1L, the long isoform of PIM-1 kinase, the splicing of which has been implicated in acute myeloid leukemia, contains a domain that consists largely of repeating SR/RS and SH/HS dipeptides (SR/SH-rich). In order to extend our knowledge on the specificity and cellular functions of SRPK1, here we investigate whether PIM-1L could act as substrate of SRPK1 by a combination of biochemical and computational approaches. Our biochemical data showed that the SR/SH-rich domain of PIM-1L was able to associate with SRPK1, yet it could not act as a substrate but, instead, inactivated the kinase. In line with our biochemical data, molecular modeling followed by a microsecond-scale all-atom molecular dynamics (MD) simulation suggests that the SR/SH-rich domain acts as a pseudo-docking peptide that binds to the same acidic docking-groove used in other SRPK1 interactions and induces inactive SRPK1 conformations. Comparative community network analysis of the MD trajectories, unraveled the dynamic architecture of apo SRPK1 and notable alterations of allosteric communications upon PIM-1L peptide binding. This analysis also allowed us to identify key SRPK1 residues, including unique ones, with a pivotal role in mediating allosteric signal propagation within the kinase core. Interestingly, most of the identified amino acids correspond to cancer-associated amino acid changes, validating our results. In total, this work provides insights not only on the details of SRPK1 inhibition by the PIM-1L SR/SH-domain, but also contributes to an in-depth understanding of SRPK1 regulation.

Changes in serum uric acid, glutathione, and amyloid-β1-42 levels in Parkinson’s disease patients and their association with disease progression and cognitive decline

Objective This study aims to evaluate the diagnostic significance of serum uric acid (UA), glutathione (GSH), and amyloid-β1-42 (Aβ1-42) levels in relation to disease progression and cognitive impairment in patients with Parkinson’s disease (PD). Methods A total of 209 PD patients with disease duration ranging from 4.0 to 6.8 years were enrolled. Based on the Hoehn-Yahr staging system, patients were classified into Early (n = 67), Medium-term (n = 70), and Advanced (n = 72) stages. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), dividing the cohort into CD (cognitive dysfunction, n = 94) and NO-CD (no cognitive dysfunction, n = 115) groups. Serum UA, GSH, and Aβ1-42 levels were analyzed for correlations with clinical data. Independent risk factors and diagnostic value were determined through multivariable logistic regression models and receiver operating characteristic curve analysis. Results Serum UA and GSH levels progressively declined with advancing disease stage, while Aβ1-42 increased. Compared to the NO-CD group, the CD group showed lower serum UA and GSH levels, and higher Aβ1-42 levels. Serum UA and GSH were inversely correlated with disease duration, levodopa equivalent daily dose, and Unified Parkinson's Disease Rating Scale scores, while Aβ1-42 showed positive correlations. UA (p = 0.006), GSH (p < 0.001), and Aβ1-42 (p = 0.040) were independent predictors of disease stage. Similarly, UA (p = 0.003), GSH (p < 0.001), and Aβ1-42 (p < 0.001) were independent predictors of cognitive dysfunction. The combined assessment of these markers demonstrated a higher area under the curve (AUC) than individual markers for disease and cognitive decline identification. Conclusions Serum UA, GSH, and Aβ1-42 are independent predictors of disease progression and cognitive decline in PD patients. Their combined use offers enhanced diagnostic accuracy for disease staging and cognitive impairment in PD.

Stoichiometry of HIV-1 Envelope Glycoprotein Protomers with Changes That Stabilize or Destabilize the Pretriggered Conformation.

The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer consists of three protomers. In response to receptor binding, the flexible Env changes its conformation to mediate virus entry into host cells. The shape-shifting ability of Env also contributes to HIV-1's capacity to evade the host immune system. The pretriggered (State-1) conformation (PTC) of Env is an important target for virus entry inhibitors and host antibodies, but is unstable and therefore incompletely characterized. Changes in Env amino acids that either stabilize or destabilize the PTC have been identified. Here, we define how many Env protomers need to be modified by these changes to achieve stabilization or destabilization of the PTC. These results can guide the placement of changes in the HIV-1 Env protomers to control the movement of the Env trimer from the PTC, allowing better characterization of this elusive conformation and testing of its utility in vaccines.

Association between change in serum uric acid and rapid decline in kidney function in China

While the elevation of serum uric acid (SUA) is acknowledged as a risk factor for chronic kidney disease, the independent extent to which variations in SUA levels are correlated with temporal changes in estimated glomerular filtration rate (eGFR) remains uncertain. In light of this uncertainty, our research endeavored to elucidate the temporal associations between change in SUA and rapid eGFR decline in China. In this longitudinal study of China’s middle-aged and elderly between 2011 and 2015, we analyzed 5421 individuals with complete SUA and eGFR data. Logistic regression was applied to evaluate the risk factors associated with a rapid eGFR decline (defined by a 5 mL/min/1.73 m2 decrease or falling to less than 15 mL/min/1.73 m2 by 2015), adjusted for age, gender, marital, residence, income, BMI, hypertension, diabetes, dyslipidemia, CRP, Hba1c, baseline eGFR and baseline SUA. Linear regression was used to evaluate the relationship between variations in SUA and changes in eGFR. After multivariable adjustments, the risk factors of a rapid eGFR decline included aging (OR per 1-year increase: 1.1, 95% CI 1.08–1.12, P < 0.001), being female, being single, having hypertension, a higher baseline eGFR, a higher baseline SUA (OR per-1 mg/dL increase: 1.68, 95% CI 1.48–1.90, P < 0.001), and increase in change in SUA (OR per-1 mg/ dL increase: 1.92,95% CI 1.71–2.16, P < 0.001). Pearson’s analysis showed a significant inverse correlation between SUA changes and eGFR decline, particularly pronounced in females, with correlation coefficients of − 0.349 for females and − 0.306 for males (95% CI − 0.347 to − 0.299, P < 0.001). A significant correlation was found between the change in SUA and the rapid decline in eGFR, with this association being particularly pronounced in females.

Natural alleles of LEAFY and WAPO1 interact to regulate spikelet number per spike in wheat

Key messageSpecific combinations ofLFY andWAPO1 natural alleles maximize spikelet number per spike in wheat. Spikelet number per spike (SNS) is an important yield component in wheat that determines the maximum number of grains that can be formed in a wheat spike. In wheat, loss-of-function mutations in LEAFY (LFY) or its interacting protein WHEAT ORTHOLOG OF APO1 (WAPO1) significantly reduce SNS by reducing the rate of formation of spikelet meristems. In previous studies, we identified a natural amino acid change in WAPO1 (C47F) that significantly increases SNS in hexaploid wheat. In this study, we searched for natural variants in LFY that were associated with differences in SNS and detected significant effects in the LFY-B region in a nested association mapping population. We generated a large mapping population and confirmed that the LFY-B polymorphism R80S is linked with the differences in SNS, suggesting that LFY-B is the likely causal gene. A haplotype analysis revealed two amino acid changes P34L and R80S, which were both enriched during wheat domestication and breeding suggesting positive selection. We also explored the interactions between the LFY and WAPO1 natural variants for SNS using biparental populations and identified significant interaction, in which the positive effect of the 80S and 34L alleles from LFY-B was only detected in the WAPO-A1 47F background but not in the 47C background. Based on these results, we propose that the allele combination WAPO-A1-47F/LFY-B 34L 80S can be used in wheat breeding programs to maximize SNS and increase grain yield potential in wheat.

Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin.

Multidrug-resistant bacterial pathogens like vancomycin-resistant Enterococcus faecium (VREfm) are a critical threat to human health1. Daptomycin is a last-resort antibiotic for VREfm infections with a novel mode of action2, but for which resistance has been widely reported but is unexplained. Here we show that rifaximin, an unrelated antibiotic used prophylactically to prevent hepatic encephalopathy in patients with liver disease3, causes cross-resistance to daptomycin in VREfm. Amino acid changes arising within the bacterial RNA polymerase in response to rifaximin exposure cause upregulation of a previously uncharacterized operon (prdRAB) that leads to cell membrane remodelling and cross-resistance to daptomycin through reduced binding of the antibiotic. VREfm with these mutations are spread globally, making this a major mechanism of resistance. Rifaximin has been considered 'low risk' for the development of antibiotic resistance. Our study shows that this assumption is flawed and that widespread rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin, a major last-resort intervention for multidrug-resistant pathogens. These findings demonstrate how unanticipated antibiotic cross-resistance can undermine global strategies designed to preserve the clinical use of critical antibiotics.

Yeast β-glucan supplementation lowers insulin resistance without altering microbiota composition compared to placebo in subjects with Type II diabetes: a phase I exploratory study.

The increased global prevalence of type II diabetes mellitus (T2DM) is associated with consumption of low fibre "Western diets". Characteristic metabolic parameters of these individuals include insulin resistance, high fasting and postprandial glucose, as well as low-grade systemic inflammation. Gut microbiota composition is altered significantly in these cohorts suggesting a causative link between diet, microbiota and disease. Dietary fibre consumption has been shown to alleviate these changes and improve glucose parameters in individuals with metabolic disease. We previously reported that yeast β-glucan (yeast beta-1,3/1,6-D-glucan; Wellmune) supplementation ameliorated hyperinsulinemia and insulin resistance in a murine model. Here we conducted a randomised, placebo-controlled, two-armed dietary fibre phase I exploratory intervention study in patients with T2DM. The primary outcome measure was alteration to microbiota composition while the secondary outcome measures included markers of glycaemic control, inflammation as well as metabolomics. Patients were supplemented with 2.5g/day of maltodextrin (placebo) or yeast β-1,3/1,6-D-glucan (treatment). Yeast β-glucan (Wellmune) lowered insulin resistance (HOMA-IR) compared to the placebo maltodextrin after 8 weeks of consumption. TNFα was significantly lower after 4 weeks of β-glucan supplementation. Significantly higher faecal concentrations of several bile acids were detected in the treatment group when compared to the placebo after 8 weeks. These included tauroursodeoxycholic acid (TUDCA) which was previously shown to improve glucose control and lower insulin resistance. Interestingly, the hypoglycaemic and anti-inflammatory effect of yeast β-glucan was independent of any changes in faecal microbiota composition or short-chain fatty acid (SCFA) levels. Our findings highlight the potential of yeast β-glucan to lower insulin resistance in patients with T2DM.

Comparative study of volatile compounds of cold-pressed oils extracted from three different oilseeds after gamma irradiation.

To investigate the effect of gamma irradiation on the volatile compounds of edible oils. Three types of oilseeds, including peanut, sesame, and flaxseed, were subjected to 8 kGy gamma irradiation, followed by cold pressing to extract their oils. The volatile compounds of the oils were isolated by simultaneous distillation extraction and analyzed by gas chromatography-mass spectrometry. A total of 91 volatile compounds were identified, which can be grouped into eight categories: hydrocarbons, aldehydes, ketones, alcohols, acids, esters, furans, and benzene derivatives. Irradiation treatment resulted in a significant increase in the levels of hydrocarbons, aldehydes, and ketones in all oil samples (p<0.05), with the greatest increase observed in hydrocarbons (4-14 times). In contrast, changes in alcohols, acids, esters, furans, and benzene derivatives were related to oilseed type. The increased hydrocarbons mainly originated from the degradation of palmitic, stearic, oleic, and linoleic acids. The irradiation resistance of the three oilseeds varied considerably, in the order: flaxseed>sesame>peanut. Based on the odor activity value, 11 key aroma compounds were selected, and (E)-2-decenal (tallow, oily, and orange), 1-octanol (soapy and oily), and 1-nonanol (floral and soapy) were only detected in the irradiated samples. Principal component analysis revealed that the oil samples of the three oilseeds could be well classified based on their key aroma compounds, and that the irradiation treatment had no remarkable effect on their intrinsic aroma.

Synergistic amelioration of obesity in high‐fat diet–fed mice by Bifidobacterium longum and green banana powder through targeting multiple pathways

AbstractLong‐term consumption of high‐fat diet (HFD) is a major significant risk factor for various diseases, including hyperlipidemia, diabetes, cardiovascular disease, and certain cancers. Recently, there has been a focus on effective dietary methods to improve lipid absorption and accumulation in the body. Simultaneously, exploring non‐pharmacological interventions to counteract the adverse consequences of obesity is crucial. Probiotics and prebiotics emerge as promising alternatives in this context, with their combined utilization yielding substantial effects surpassing those achieved by individual application alone. The aim of this study was to investigate the combined effects of Bifidobacterium longum (BL) SYP‐B4138 and green banana powder (GBP) on HFD‐induced obesity while exploring their underlying mechanisms. The findings demonstrated that the combined intervention exhibited significantly greater efficacy than BL or GBP alone, including in mitigating weight gain and organ weight among obese mice, while also improving lipid profile, glucose tolerance, and inflammation levels. Furthermore, it effectively reduced liver fat accumulation. The mechanism study revealed that the combined intervention increased the expression of gene‐related lipid metabolism, such as Pparα, Cpt1a, Fxr, Cyp7a1, and Bsep, while decreasing expression of the regulatory genes involved in fat synthesis, Acc1, Srebpf1, and Pparγ. The correlation analysis of gut microbes and metabolites suggests that the combined effect of BL and GBP can reverse the intestinal microecological imbalance, leading to changes in bile acids, glycerophospholipids, and other related metabolites. Overall, this study demonstrates that BL combined with GBP can effectively alleviate dietary obesity, highlighting its potential as a non‐pharmacological intervention for weight reduction.

Insights into Genetic and Antigenic Characteristics of Influenza A(H1N1)pdm09 Viruses Circulating in Sicily During the Surveillance Season 2023-2024: The Potential Effect on the Seasonal Vaccine Effectiveness.

After disruption in the influenza circulation due to the emergence of SARS-CoV-2, the intensity of seasonal outbreaks has returned to the pre-pandemic levels. This study aimed to evaluate the evolution and variability of whole-genome sequences of A(H1N1)pdm09, the predominant influenza virus in Sicily (Italy) during the season 2023-2024. The potential vaccine efficacy was calculated using the pepitope model based on amino acid changes in the dominant epitope of hemagglutinin. The HA gene sequences showed several amino acid substitutions, some of which were within the major antigenic sites. The phylogenetic analysis showed that Sicilian strains grouped into two main genetic clades (6B.1A.5a.2a.1 and 6B.1A.5a.2a) and several subclades. Notably, about 40% of sequences partially drifted from the WHO-recommended vaccine strain A/Victoria/4897/2022 for the Northern Hemisphere. These sequences mostly belonged to the subclades C.1.8 and C.1.9 and harboured the amino acid mutations responsible for the modest predicted vaccine efficacy (E = 38.12% of 53%, pepitope = 0) against these viruses. Amino acid substitutions in other gene segments were also found. Since influenza viruses are constantly evolving, genomic surveillance is crucial in monitoring their molecular evolution and the occurrence of genetic and antigenic changes, and, thus, their potential impact on vaccine efficacy.