Effects of salinity and betaine addition on anaerobic granular sludge properties and microbial community succession patterns in organic saline wastewater.

In this study, the effects of different salinity gradients and addition of compatible solutes on anaerobic treated effluent water qualities, sludge characteristics and microbial communities were investigated. The increase in salinity resulted in a decrease in particle size of the granular sludge, which was concentrated in the range of 0.5-1.0 mm. The content of EPS (extracellular polymeric substances) in the granular sludge gradually increased with increasing salinity and the addition of betaine (a typical compatible solute). Meanwhile, the microbial community structure was significantly affected by salinity, with high salinity reducing the diversity of bacteria. At higher salinity, Patescibacteria and Proteobacteria gradually became the dominant phylum, with relative abundance increasing to 13.53% and 12.16% at 20 g/L salinity. Desulfobacterota and its subordinate Desulfovibrio, which secrete EPS in large quantities, dominated significantly after betaine addition.Their relative abundance reached 13.65% and 7.86% at phylum level and genus level. The effect of these changes on the treated effluent was shown as the average chemical oxygen demand (COD) removal rate decreased from 82.10% to 79.71%, 78.01%, 68.51% and 64.55% when the salinity gradually increased from 2 g/L to 6, 10, 16 and 20 g/L. At the salinity of 20 g/L, average COD removal increased to 71.65% by the addition of 2 mmol/L betaine. The gradient elevated salinity and the exogenous addition of betaine played an important role in achieving stability of the anaerobic system in a highly saline environment, which provided a feasible strategy for anaerobic treatment of organic saline wastewater.

Synergistic effects of melatonin and glycine betaine on seed germination, seedling growth, and biochemical attributes of maize under salinity stress.

Salinity stress represents a major threat to crop production by inhibiting seed germination, growth of seedlings, and final yield and, therefore, to the social and economic prosperity of developing countries. Recently, plant growth-promoting substances have been widely used as a chemical strategy for improving plant resilience towards abiotic stresses. This study aimed to determine whether melatonin (MT) and glycine betaine (GB) alone or in combination could alleviate the salinity-induced impacts on seed germination and growth of maize seedlings. Increasing NaCl concentration from 100 to 200 mM declined seed germination rate (4.6-37.7%), germination potential (24.5-46.7%), radical length (7.7-40.0%), plumule length (2.2-35.6%), seedling fresh (1.7-41.3%) and dry weight (23.0-56.1%) compared to control (CN) plants. However, MT and GB treatments lessened the adverse effects of 100 and 150 mM NaCl and enhanced germination comparable to control plants. In addition, results from the pot experiments show that 200 mM NaCl stress disrupted the osmotic balance and persuaded oxidative stress, presented by higher electrolyte leakage, hydrogen peroxide, superoxide radicals, and malondialdehyde compared to control plants. However, compared to the NaCl treatment, NaCl+MT+GB treatment decreased the accumulation of malondialdehyde (24.2-42.1%), hydrogen peroxide (36.2-44.0%), and superoxide radicals (20.1-50.9%) by up-regulating the activity of superoxide dismutase (28.4-51.2%), catalase (82.2-111.5%), ascorbate peroxidase (40.3-59.2%), and peroxidase (62.2-117.9%), and by enhancing osmolytes accumulation, thereby reducing NaCl-induced oxidative damages. Based on these findings, the application of MT+GB is an efficient chemical strategy for improving seed germination and growth of seedlings by improving the physiological and biochemical attributes of maize under 200 mM NaCl stress.

Glycine betaine: A multifaceted protectant against salt stress in Indian mustard through ionic homeostasis, ROS scavenging and osmotic regulation.

Salt stress is a prevalent environmental issue that disrupts the redox balance and metabolic processes in plants, leading to reduced crop growth and productivity. Currently, over 6.74 million hectares in India are salt-affected, and about 75% of this land lies in states that are the major cultivators of edible oilseed crops (rapeseed-mustard). Therefore, this study focused on the efficacy of glycine betaine (GB) supplementation in mitigating the detrimental effects of salt stress in Brassica juncea L. (Indian mustard) plants. Indian mustard plants were subjected to salt stress [0, 50, 100, and 150 mM sodium chloride] 20 days after sowing (DAS), while a foliar spray of 20 mM GB was applied to the foliage at 50 and 70 DAS. The data showed that salt stress substantially reduced growth, photosynthetic rate, membrane stability, and yield by significantly increasing lipid peroxidation, ion toxicity, cell death, electrolyte leakage, and reactive oxygen species accumulation that triggered oxidative stress. Supplementation with 20 mM GB provided tolerance to plants against salt-induced toxicity since it substantially increased growth, biomass, water content, nutrient uptake, and photosynthetic efficiency. Additionally, GB enhances the accumulation of osmolytes, enhances the antioxidant defence system, improves ionic balance, and enhances cell viability. Taken together, the obtained data provides deeper insights into the beneficial effect of the exogenous GB application that could have biotechnological uses to enhance crop stress tolerance in challenging environments.

Gut microbiota metabolites and risk of major adverse cardiovascular events and death: A systematic review and meta-analysis.

BACKGROUND: Gut microbial metabolites such as trimethylamine N-oxide (TMAO) and its precursors, namely betaine, L-carnitine, and choline, have been implicated as risk factors for cardiovascular events and mortality development. Therefore, we aim to perform a systematic review and meta-analysis to assess the validity of these associations. METHODS: MEDLINE and Scopus were queried from their inception to August 2023 to identify studies that quantified estimates of the associations of TMAO with the development of major adverse cardiovascular events (MACE) or death. A random-effects meta-analysis was conducted to pool unadjusted or multivariable-adjusted hazard ratios (HR) and their 95% confidence intervals. The primary endpoint was the risk of MACE and all-cause death. RESULTS: 30 prospective observational studies (n = 48 968) were included in the analysis. Elevated TMAO levels were associated with a significantly greater risk of MACE and all-cause death compared to low TMAO levels (HR: 1.41, 95% CI 1.2-1.54, P < .00001, I2 = 43%) and (HR: 1.55, 95% CI 1.37-1.75, P < .00001, I2 = 46%), respectively. Furthermore, high levels of either L-carnitine or choline were found to significantly increase the risk of MACE. However, no significant difference was seen in MACE in either high or low levels of betaine. CONCLUSION: Elevated concentrations of TMAO were associated with increased risks of MACE and all-cause mortality. High levels of L-carnitine/choline were also significantly associated with an increased risk of MACE. However, no significant difference was found between high or low levels of betaine for the outcome of MACE.

Prophylactic Effects of Betaine on Depression and Anxiety Behaviors in Mice with Dextran Sulfate Sodium-Induced Colitis.

Ulcerative colitis (UC) is a typical type of inflammatory bowl disease, which is accompanied by an increased risk of depression and anxiety-related psychological symptoms. Betaine is a naturally derived compound that can function as an anti-inflammatory drug and a neuromodulator. In-depth exploration of the potential role of betaine in treating UC-related depression and anxiety is crucial. This study aimed to elucidate the effects of betaine on UC-related depression and anxiety and clarify the underlying mechanisms. A dextran sulfate sodium (DSS)-induced mice model was established by 4% DSS drinking ad libitum for 7 days. The colonic injury was measured using hematoxylin-eosin (HE) staining and Alcian blue-periodic acid Schiff (AB-PAS) staining. Depression and anxiety-like behaviors were separately evaluated using a forced swimming test (FST), a tail suspension test (TST), a light-dark box test (LDBT), and an open field test (OFT). Immunohistochemistry was used to detect DNA damage and neurogenesis in the hippocampus. Western blotting was applied to detect the protein levels of macrophage polarization in mice colons and the alteration of mitochondrial dysfunction and the cGAS-STING pathway in the hippocampus. Betaine strongly alleviated mucosal structural disorder and mucin secretion reduction and promoted M2-macrophage polarization in the colon of DSS-treated mice. In addition, betaine could mitigate depression- and anxiety-like behaviors in DSS-treated mice, reduce the DNA damage and mitochondrial dysfunction, and inhibit the cGAS-STING signaling pathway. Our study reveals the antidepression/anxiety effects of betaine and further demonstrates the potential mechanism by which betaine inhibits DNA damage and mitochondrial dysfunction to block the cGAS-STING pathway, thereby repairing neurogenesis in the hippocampus.

Bioinspired Sulfobetaine Borneol Fluorinated Amphiphilic Polymers for Marine Antifouling and Fouling Release Applications.

The development of nontoxic antifouling coatings in static marine environments is urgent. Herein, the successful synthesis of sulfobetaine borneol fluorinated polymers (PEASBF) by a free radical polymerization method is reported. The PEASBF coatings exhibit outstanding antifouling activity, which effectively resists the adhesion of Bovine serum albumin (FITC-BSA adhesion rate: 0.5%), Pseudomonas sp. (Biofilm: 1.3 absorbance) and Navicula sp. (Diatom attachment rate: 33%). More importantly, the PEASBF coatings display outstanding fouling release properties, achieving a release rate of 98% for Navicula sp., and the absorbance of the Pseudomonas sp. biofilm is only 0.2 under 10 Pa shear stress. XPS and MD studies showed that the fluorinated/isobornyl groups induce more sulfobetaine groups to migrate toward polymer surfaces for intensify antifouling. Additionally, the chiral stereochemical structure of borneol enhances antifouling and fouling release ability of amphiphilic polymers. Therefore, the PEASBF has the potential for static marine antifouling applications.

Understanding retention and intra-particle diffusivity of alkylsulfobetaine-bonded Ethylene Bridged Particles with different mesopore sizes for hydrophilic interaction liquid chromatography applications.

The role of the average pore diameter (APD) of 1.7µm AtlantisTM Premier BEHTM Particles derivatized with a zwitterionic group (propylsulfobetaine) on the efficiency of their 2.1 × 50 mm hydrophilic interaction liquid chromatography (HILIC) packed columns is investigated experimentally. Van Deemter plots for toluene (neutral, hydrophobic), cytosine (neutral, polar), tosylate (negatively charged), bretylium and atenolol (positively charged) were measured on three HILIC columns packed with BEH Z-HILIC Particles having APDs of 95 Å, 130 Å, and 300 Å. The intraparticle diffusivities of the analytes across these three BEH Z-HILIC Particles were measured by the peak parking method. The experimental data reveal that the slope of the C-branch of the van Deemter plots can be reduced by factors of about 15 for toluene, 2.5 for cytosine, 6 for atenolol, 5 for tosylate, and 14 for bretylium with increasing the APD from 95 Å to 300 Å. This observation is explained by: (1) the reduced amount of the highly viscous water diffuse layer and subsequent increase of the amount of acetonitrile-rich eluent in the mesopores, (2) the localized electrostatic adsorption of the retained analytes onto the zwitterion-bonded BEH Particles, and (3) depletion/excess of the analytes into the water diffuse layer. A general model of intraparticle diffusivity was then proposed to account for the impact of the APD of Z-HILIC Particles on the solid-to-liquid mass transfer resistance of small molecules. The model highlights the relevance of the thickness of the water diffuse layer, the access of the bulk eluent into the mesopore, the localized electrostatic adsorption, and the partitioning constant of the retained analyte between the bulk eluent and the water diffuse layer.

Breast gel based on Boswellia serrata, Betaine and myo-Inositol improves cyclic mastodynia in fertile women: A retrospective clinical study.

BACKGROUND: The management of mastodynia plays a central role in improving women quality of life. Despite its high occurrence, specific therapeutic guidelines for mastalgia are still lacking. Available therapies include unspecific anti-inflammatories, even though they may often expose to undesirable effects and low compliance. OBJECTIVE: The aim of this study was to highlight the efficacy of the topical application of combined natural molecules including Boswellia serrata, Betaine and myo-Inositol in improving cyclic mastalgia. METHODS: In this retrospective pilot clinical study, patients with cyclic mastalgia applied a specific breast gel for three months. The severity of the pain was measured through the Visual Analogue Score (VAS) in the treated group compared to untreated one. Treated patients also filled in a questionnaire evaluating acceptance and safety of the breast gel. RESULTS: This pilot clinical study demonstrated for the first time the efficacy of the topical application of a breast gel based on Betaine, Boswellia serrata, and myo-Inositol in improving cyclic mastodynia. The completed questionnaires also revealed high levels of acceptance, as both safety and compliance. CONCLUSIONS: Besides confirming the positive effects of these natural molecules in the management of conditions affecting breast physiology - so far evaluated as oral supplementation - the obtained results pave the way for further studies supporting the use of such molecules as a tailored medical device in the management of breast pain, thus also opening toward a combined oral and topical approach.

Exploring antiviral activity of Betanin and Glycine Betaine against dengue virus type-2 in transfected Hela cells.

Dengue virus (DENV) infection is a worldwide public health concern infecting approximately 400 million individuals and about 40,000 mortalities yearly. Despite this, no licensed or readily available antiviral medication is currently available specifically for DENV infection, and therapy is typically symptomatic. Therefore, the objective of the study was to investigate the antiviral activity of Beta vulgaris L. phytoconstituents against DENV-2 targeting NS3 protein. The antiviral activity of phytochemicals was examined through virtual ligand-based screening, antiviral inhibition and dosage response assays, western blotting analysis and MD simulations. We conducted toxicological, and pharmacokinetic analysis to assess plant-based natural compound's efficacy, safety, and non-toxic doses. Molecular docking and MD simulation results revealed that the nonstructural protein-3 (NS3) might prove as a funamental target for Betanin and Glycine Betaine against Dengue virus. Betanin and Glycine betaine were initially studied for their non-toxic doses in HeLa, CHO, and Vero cells via MTT assay. HeLa cells were transiently transfected with cloned vector pcDNA3.1/Zeo(+)/DENV-2 NS3 along with non-toxic doses (80 µM-10 µM) of selected phytochemicals. The dose-response assay illustrated downregulated expression of DENV-2 NS3 gene after administration of Betanin (IC50 = 4.35 µM) and Glycine Betaine (IC50 = 4.49 µM). Dose response analysis of Betanin (80 µM-10 µM) depicted the significant inhibition of NS3 protein expression as well. These results suggested downregulated expression of DENV-2 NS3 at mRNA and protein level portraying the DENV replication inhibition. Based on our study findings, NS3 protease is depicted as distinctive DENV-2 inhibitor target. We will channel our study further into in vitro characterization employing the mechanistic study to understand the role of host factors in anti-flavi therapeutic.

Condensed tannins from Pinus radiata bark: Extraction and their nanoparticles preparation in water by green method.

This work reports for the first time the production of condensed tannin nanoparticles stable in water via modification with glycine betaine. Pine bark, as a byproduct from the paper industry, was used as a source of condensed tannins of high molecular weight. Different glycine betaine concentrations were tested to produce condensed tannin nanoparticles, and the obtained nanoparticles were subjected to several characterization techniques (Dynamic Light Scattering, Field emission scanning electron microscopy, Zeta potential, Fourier transform infrared spectroscopy-Attenuated total reflectance, thermogravimetric analysis). The results showed that the highest stability possessed nanoparticles with 40 wt% glycine betaine. The average particle size distribution evaluated by scanning microscopy was 124 nm. Besides, the glycine betaine-modified condensed tannin nanoparticles demonstrated higher thermal stability with the starting degradation temperature at 238 °C. Finally, obtained nanoparticles showed an antioxidant capacity of 34,209 ± 2194 µmol ET/100 g and low cytotoxicity towards healthy human cells, representing the high potential to be used as a carrier of active compounds in agriculture, food, drug and medical sector.

Effect of anionic groups in zwitterionic hydrophilic stationary phases on their chromatographic characteristics.

The structure of zwitterion has great impact on the separation properties of zwitterionic hydrophilic stationary phases. To better understand the role of anionic groups of zwitterions, a novel carboxybetaine-based zwitterionic monolithic column was first prepared through thermo-initiated copolymerization of functional monomer (3-acrylamidopropyl)-dimethyl-(2-carboxymethyl) ammonium (CBAA) and crosslinker ethylene dimethacrylate (EDMA) within 100 µm ID capillary. The optimal poly(CBAA-co-EDMA) monolithic column exhibited satisfactory mechanical and chemical stability, good repeatability, high column efficiency (96,000 plates/m), and excellent separation performance for different classes of polar compounds (i.e., phenols, monophosphate nucleotides, urea and allantoin). A comparative study was then performed among three zwitterionic hydrophilic stationary phases containing different anionic groups, i.e. poly(CBAA-co-EDMA) (carboxybetaine), poly(2-{2-(methacryloyloxy) ethyldimethylammonium}ethyl n-butyl phosphate-co-EDMA) (phosphocholine), and poly(N,N-dimethyl-N-(3-methacrylamidopropyl)-N-(3-sulfopropyl) ammonium betaine-co-EDMA) (sulfobetaine) using benzoic acid derivatives, amine compounds, nucleobases and nucleosides as model analytes. The carboxybetaine-based monolithic column exhibited much higher positive zeta-potential and hydrophilicity, which endows it with a stronger retention capacity for acidic and neutral compounds, but sulfobetaine-based monolithic column exhibited much higher selectivity and retention capacity for the amines. Moreover, their enrichment efficiencies for N-glycopeptides were also evaluated based on their different hydrophilicity, and it was observed that the poly(CBAA-co-EDMA) monolithic material captured 4-8 times more N-glycopeptides compared to the other two materials.

A Natural deep eutectic solvent as an effective material for dual debridement and antibiofilm effects in chronic wound treatment.

In chronic wound treatment, the debridement of devitalized tissue and the eradication of the biofilm must balance aggressiveness with care to protect regenerating tissues. In this study, urea, a potent chaotropic molecule, was modulated through the formation of a Natural Deep Eutectic Solvent (NADES) with betaine to develop a new debriding material (BU) suitable for application into injured dermal tissues. To evaluate BU's debriding capacity, along with its antibiofilm effect and biocompatibility, pre-clinical to clinical methods were employed. In vitro determinations using artificial and clinical slough samples indicate that BU has a high debriding capacity. Additionally, BU's de-structuring effects lead to a strong antibiofilm capability, demonstrated by a reduced bacterial load compared to the antiseptic PHMB-Betaine or medical honey, evaluated in artificial slough and ex vivo human skin. Furthermore, BU's efficacy was evaluated in a murine model of diabetic wound, demonstrating significant effects on debriding and antibiofilm capacity, similar to those observed in PHMB-Betaine and medical honey-treated animals. Finally, BU was clinically evaluated in leg ulcers, showing superiority in reduction of bacterial load and wound area compared to honey, with no adverse effects. Thus, BU represents a simple and non-biocidal option that could contributes to chronic wound care.

Effects of betaine supplementation on dry matter intake, milk characteristics, plasma non-esterified fatty acids, and ß-hydroxybutyric acid in dairy cattle: a meta-analysis.

Betaine supplementation in dairy cattle has gained attention due to its potential benefits to production and health as a methyl donor, which can play a crucial role in the metabolism of dairy cows. The objective of the current meta-analysis was to quantify the effects of betaine supplementation on milk production, composition, ß-hydroxybutyric acid (BHBA), and non-esterified fatty acids (NEFA). A systematic literature search was carried out, all relevant studies were retrieved, and the meta-analysis was carried out. The mean difference (MD) for dry matter intake (DMI) using the random-effects model was 0.499 kg/d (P < 0.0001). The subgroup analysis indicated that supplementing betaine in heat-stressed cows increased DMI by 0.584 kg/d (P < 0.001), while in cows not exposed to heat stress, DMI was increased by 0.381 kg/d (P = 0.007). The energy-corrected milk (ECM) increased by 1.36 kg/d (P < 0.0001). The milk fat yield was significantly increased in betaine-supplemented cows (MD = 0.040 kg/d, 95% CI = 0.015 to 0.065). The milk protein yield (kg/d) (MD = 0.014, P = 0.138) was increased (MD = 0.035, P = 0.0005) by betaine supplementation. The lactose yield (kg/d) was also significantly higher (MD = 0.055, P = 0.020) in betaine-supplemented cows. The standardized mean difference (SMD) for NEFA (SMD = - 0.447, 95% CI = - 1.029 to 0.135, P = 0.114) and BHBA (SMD = - 0.130, 95% CI = - 0.491 to 0.234). In conclusion, the findings from this meta-analysis suggest that betaine supplementation positively influences DMI, ECM, milk fat yield, milk lactose yield, and milk protein yield. Subgroup analysis further indicated that the positive effects on DMI are greater in heat-stressed cows compared to those not exposed to heat stress. The analysis did not find significant effects on the levels of NEFA or BHBA, suggesting that betaine supplementation may not directly influence these metabolic parameters.

The aim of this meta-analysis was to examine the effects of dietary betaine supplementation on dairy cows' dry matter intake, milk production, milk composition, non-esterified fatty acids, and ß-hydroxybutyric acid. The results indicated that the supplementation of betaine increased dry matter intake (+0.584 kg/d/cow), energy-corrected milk (+1.36 kg/d), milk fat yield (+ 0.040 kg/d), milk protein yield (+ 0.014 kg/d), and lactose yield (+ 0.055 kg/d). ß-Hydroxybutyric acid and plasma non-esterified fatty acids were not influenced by betaine supplementation in dairy cattle.

In ovo betaine injection improves breast muscle growth in newly hatched goslings through FXR/IGF-2 pathway.

Betaine has been shown to enhance growth performance and increase breast muscle yield in ducks and broilers through various mechanisms, including the modification of DNA methylation. However, the impact of in ovo betaine injection on muscle growth in newly hatched goslings remains unclear. In this study, fifty eggs were injected with saline or betaine at 7.5 mg/egg prior to incubation, and the subsequent effects on breast muscle growth in the newly hatched goslings were investigated. Betaine significantly increased (P < 0.05) the hatch weight, breast muscle weight, and breast muscle index, accompanied by an augmentation in muscle bundle cross-sectional area. Concurrently, betaine significantly upregulated (P < 0.05) the expression levels of myogenic regulatory factors, including myogenin (MyoG) and paired box 7 (Pax7) both mRNA and protein, while downregulating (P < 0.05) the mRNA and protein levels of myostatin (MSTN). Histological analysis revealed a higher abundance of proliferating cell nuclear antigen (PCNA) and Pax7 immune-positive cells in the breast muscle of the betaine group, consistent with elevated PCNA and Pax7 mRNA and protein levels. Additionally, significantly increased (P < 0.05) contents of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) were observed in the breast muscle of the betaine group, so was mRNA expression of IGF-1, IGF-2, and insulin-like growth factor 1 receptor (IGF-1R). Betaine also significantly in8creased (P < 0.05) global DNA methylation of the breast muscle, accompanied by enhanced mRNA and protein levels of methionine cycle and DNA methylation-related enzymes, Interestingly, the promoter regions of IGF-1, IGF-2, and IGF-1R genes were significantly hypomethylated (P < 0.05). Moreover, in ovo betaine injection significantly upregulated (P < 0.05) the protein level of farnesoid X receptor (FXR) in breast muscle and FXR binding to the promoter of IGF-2 gene. These findings suggest that in ovo betaine injection promotes breast muscle growth during embryonic development in goslings through the FXR-mediated IGF-2 pathway, ultimately improving hatch weight and breast muscle weight.

Betaine and feed restriction as potential mitigation strategies against heat stress in two strains of laying hens.

Climate change is increasingly manifesting in temperate regions. Laying hens are highly sensitive to heat stress and mitigation strategies should be implemented to reduce the negative effects. The goal of this experiment was to evaluate the effects of betaine in drinking water (0.55 g/L) and 4 h feed restriction during peak heat stress on laying performance, egg quality, blood gas parameters, body temperature (Tb), and oxidative stress in 2 different breeds of laying hens. Therefore, 448 ISA Brown hens (25 wk) and 448 Lohmann LSL classic laying hens (26 wk) were housed in 128 cages (7 hens/cage). Thermoneutral (TN) data was collected for 21 d before cyclic heat stress (HS) (21d; 32 ± 2°C; 6 h daily). During HS, hens were divided into 4 treatments: 1) feed restriction (FR), 2) betaine supplementation in drinking water (BET), 3) feed restriction and betaine supplementation in drinking water (FR-BET), or 4) control (CON). The effects were evaluated after 1 wk of HS (acute heat stress; AHS) and 3 wk of HS (chronic heat stress; CHS). Laying rate and egg mass (EM) diminished during CHS but decreased more in white than brown hens (2.78% and 1.94%; -1.57% and -0.81%, respectively; P = 0.004) and remained unaltered by BET or FR. During AHS, average daily feed intake (ADFI) increased compared to TN, but the increase was higher in white than brown hens (6.36% and 2.62%, respectively; P = 0.001). Egg shell quality deteriorated during AHS and CHS, but was most affected in white hens, FR or BET did not impact this. Blood pCO2, HCO3- and base excess significantly decreased during AHS and CHS, but pH and iCa were unaltered. Blood glucose increased in white hens during AHS compared to TN (P < 0.001), while plasma malondialdehyde increased in brown hens (P < 0.001). Results indicated that laying hens experienced HS, but breed differences were observed and white hens were generally most affected. FR affected feed conversion ratio negatively during CHS. However, FR and BET could not improve laying performance, egg quality, Tb, or blood parameters during HS.

Dietary betaine supplementation improved egg quality and gut microbes of laying hens under dexamethasone-induced oxidative stress.

Oxidative stress is a frequent concern in the breeding of laying hens, and limit the healthy development of poultry. Dexamethasone (DXM) has been demonstrated to induce oxidative stress. Conversely, betaine is an alkaloid with a potent antioxidant activity. The study was designed to investigate the ameliorative effect of betaine on DXM-induced oxidative stress in laying hens. The results revealed that DXM treatment significantly decreased laying rate, shell strength, albumen height, Haugh unit, egg weight, folk weight and albumen weight, alongside increased malondialdehyde (MDA) and decreased total antioxidant capacity (T-AOC) in serum and liver (P < 0.05). In contrast, dietary betaine addition reversed those parameters mentioned above (P < 0.05). Hepatic RNA-seq analysis showed that there existed 110 up- and 88 down-regulated genes in DXM group when compared with the control. Meanwhile there were 117 upregulation and 169 downregulation genes in BT group when compared with DXM group. Besides, we found that dietary betaine addition significantly down-regulated cell adhesion molecules, glycerolipid metabolism and glycolysis gluconeogenesis pathways. In addition, a total of 44 and 94 differential metabolites were identified respectively from Con vs. DXM and DXM vs BT. More importantly, dietary betaine addition significantly increased the levels of pantothenic acid, gamma-Aminobutyric acid, equol and choline, all of which were related to antioxidant and anti-inflammatory properties. Furthermore, gut microbiota analysis indicated that the Chao and Observed_species indexes were remarkably higher in BT group (P<0.05). Heatmap analysis revealed that Subdoligranulum, Prevotella, Blautia, YRC22, Bacteroides, Ruminococcus and Coprococcus were notably restored in BT group (P<0.05). Taken together, our findings collectively illustrate that dietary betaine addition could attenuate DXM-induced oxidative stress, improve egg quality and gut microbes of laying hens.

Structure and mechanism of the osmoregulated choline transporter BetT.

The choline-glycine betaine pathway plays an important role in bacterial survival in hyperosmotic environments. Osmotic activation of the choline transporter BetT promotes the uptake of external choline for synthesizing the osmoprotective glycine betaine. Here, we report the cryo-electron microscopy structures of Pseudomonas syringae BetT in the apo and choline-bound states. Our structure shows that BetT forms a domain-swapped trimer with the C-terminal domain (CTD) of one protomer interacting with the transmembrane domain (TMD) of a neighboring protomer. The substrate choline is bound within a tryptophan prism at the central part of TMD. Together with functional characterization, our results suggest that in Pseudomonas species, including the plant pathogen P. syringae and the human pathogen Pseudomonas aeruginosa, BetT is locked at a low-activity state through CTD-mediated autoinhibition in the absence of osmotic stress, and its hyperosmotic activation involves the release of this autoinhibition.

Trimethylamine N-Oxide and Related Gut Microbe-Derived Metabolites and Incident Heart Failure Development in Community-Based Populations.

BACKGROUND: Growing evidence indicates that trimethylamine N-oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine N-oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine) affect incident heart failure (HF). METHODS: We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites. Cox proportional hazard models were used to examine the associations between metabolites and incident HF, adjusted for cardiovascular disease risk factors. RESULTS: In all, 2102 cases of HF occurred over a median follow-up of 15.9 years. After adjusting for traditional risk factors, higher concentrations of trimethylamine N-oxide (hazard ratio, 1.15 [95% CI, 1.09-1.20]; P<0.001), choline (hazard ratio, 1.44 [95% CI, 1.26-1.64]; P<0.001), and crotonobetaine (hazard ratio, 1.24 [95% CI, 1.16-1.32]; P<0.001) were associated with increased risk for incident HF. After further adjustment for renal function (potential confounder or mediator), these associations did not reach Bonferroni-corrected statistical significance (P=0.01, 0.049, and 0.006, respectively). Betaine and carnitine were nominally associated with a higher incidence of HF (P<0.05). In exploratory analyses, results were similar for subtypes of HF based on left ventricular ejection fraction, and associations appeared generally stronger among Black and Hispanic/Latino versus White adults, although there were no interactions for any metabolites with race. CONCLUSIONS: In this pooled analysis of 2 well-phenotyped, diverse, community-based cohorts, circulating concentrations of gut microbe-derived metabolites such as trimethylamine N-oxide, choline, and crotonobetaine were independently associated with a higher risk of developing HF. REGISTRATION: URL: https://www.clinicaltrials.gov/; Unique identifiers: NCT00005133 and NCT00005487.

Studies on Sorption and Release of Doxycycline Hydrochloride from Zwitterionic Microparticles with Carboxybetaine Moieties.

The aim of this study was to examine the use of zwitterionic microparticles as new and efficient macromolecular supports for the sorption of an antibiotic (doxycycline hydrochloride, DCH) from aqueous solution. The effect of relevant process parameters of sorption, like dosage of microparticles, pH value, contact time, the initial concentration of drug and temperature, was evaluated to obtain the optimal experimental conditions. The sorption kinetics were investigated using Lagergren, Ho, Elovich and Weber-Morris models, respectively. The sorption efficiency was characterized by applying the Langmuir, Freundlich and Dubinin-Radushkevich isotherm models. The calculated thermodynamic parameters (ΔH, ΔS and ΔG) show that the sorption of doxycycline hydrochloride onto zwitterionic microparticles is endothermic, spontaneous and favorable at higher temperatures. The maximum identified sorption capacity value is 157.860 mg/g at 308 K. The Higuchi, Korsmeyer-Peppas, Baker-Lonsdale and Kopcha models are used to describe the release studies. In vitro release studies show that the release mechanism of doxycycline hydrochloride from zwitterionic microparticles is predominantly anomalous or non-Fickian diffusion. This study could provide the opportunity to expand the use of these new zwitterionic structures in medicine and water purification.

Dysregulation of hepatic one-carbon metabolism in classical homocystinuria: Implications of redox-sensitive DHFR repression and tetrahydrofolate depletion for pathogenesis and treatment.

Cystathionine beta-synthase-deficient homocystinuria (HCU) is a life-threatening disorder of sulfur metabolism. HCU can be treated by using betaine to lower tissue and plasma levels of homocysteine (Hcy). Here, we show that mice with severely elevated Hcy and potentially deficient in the folate species tetrahydrofolate (THF) exhibit a very limited response to betaine indicating that THF plays a critical role in treatment efficacy. Analysis of a mouse model of HCU revealed a 10-fold increase in hepatic levels of 5-methyl -THF and a 30-fold accumulation of formiminoglutamic acid, consistent with a paucity of THF. Neither of these metabolite accumulations were reversed or ameliorated by betaine treatment. Hepatic expression of the THF-generating enzyme dihydrofolate reductase (DHFR) was significantly repressed in HCU mice and expression was not increased by betaine treatment but appears to be sensitive to cellular redox status. Expression of the DHFR reaction partner thymidylate synthase was also repressed and metabolomic analysis detected widespread alteration of hepatic histidine and glutamine metabolism. Many individuals with HCU exhibit endothelial dysfunction. DHFR plays a key role in nitric oxide (NO) generation due to its role in regenerating oxidized tetrahydrobiopterin, and we observed a significant decrease in plasma NOx (NO2 + NO3) levels in HCU mice. Additional impairment of NO generation may also come from the HCU-mediated induction of the 20-hydroxyeicosatetraenoic acid generating cytochrome CYP4A. Collectively, our data shows that HCU induces dysfunctional one-carbon metabolism with the potential to both impair betaine treatment and contribute to multiple aspects of pathogenesis in this disease.