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.

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.

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.

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.

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.

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.

Betaine improves METH-induced depressive-like behavior and cognitive impairment by alleviating neuroinflammation via NLRP3 inflammasome inhibition.

Methamphetamine abuse has been associated with central nervous system damage, contributing to the development of neuropsychiatric disorders such as depressive-like behavior and cognitive impairment. With the escalating prevalence of METH abuse, there is a pressing need to explore effective therapeutic interventions. Thus, the objective of this research was to investigate whether betaine can protect against depressive-like behavior and cognitive impairment induced by METH. Following intraperitoneal injections of METH in mice, varying doses of betaine were administered. Subsequently, the behavioral responses of mice and the impact of betaine intervention on METH-induced neural damage, synaptic plasticity, microglial activation, and NLRP3 inflammatory pathway activation were assessed. Administration 30 mg/kg and 100 mg/kg of betaine ameliorated METH-induced depressive-like behaviors in the open field test, tail suspension test, forced swimming test, and sucrose preference test and cognitive impairment in the novel object recognition test and Barnes maze test. Moreover, betaine exerted protective effects against METH-induced neural damage and reversed the reduced synaptic plasticity, including the decline in dendritic spine density, as well as alterations in the expression of hippocampal PSD95 and Synapsin-1. Additionally, betaine treatment suppressed hippocampal microglial activation induced by METH. Likewise, it also inhibited the activation of the hippocampal NLRP3 inflammasome pathway and reduced IL-1ß and TNF-α release. These results collectively suggest that betaine's significant role in mitigating depressive-like behavior and cognitive impairment resulting from METH abuse, presenting potential applications in the prevention and treatment of substance addiction.

Enhancing biofilm resistance and preserving optical translucency of 3D printed clear aligners through carboxybetaine-copolymer surface treatment.

OBJECTIVES: This study aimed to use a carboxybetaine methacrylate (CBMA) copolymer solution to surface treat 3D printed clear aligners at different fabrication stages, to impart antifouling properties, and assess the surface treatment at various fabrication stages' impact on physico-mechanical characteristics. METHODS: Surface treatments using a blend of 2-hydroxyethyl methacrylate (HEMA) and CBMA, termed CCS, were performed at various stages of 3D printed clear aligner fabrication. Experimental groups, CB1, CB2, and CB3, were determined by the stage of surface treatment during post-processing. CB1, CB2, and CB3 received treatment before post-curing, after post-curing, and after post-processing, respectively. Untreated samples served as controls. Physical and mechanical properties were assessed through tensile testing, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and UV-Vis spectroscopy. The surface was further characterized through scanning electron microscopy and contact angle measurements. The cytotoxicity was assessed with 7-day elution and agar diffusion assays. Lastly, bacterial biofilm resistance was evaluated using confocal laser scanning microscopy. Crystal violet assay was performed using Streptococcus mutans. RESULTS: Surface treatment during CB1 stage exerted the most significantly unfavorable influence on properties of the 3D printed aligner resin. CB2 samples showed the maximum preservation of translucency even after 7-day aging. CB2 and CB3 phases showed enhanced hydrophilicity of sample surfaces with reduced adhesion of multispecies biofilm and S. mutans. SIGNIFICANCE: Application of CCS surface treatment immediately after post-curing (CB2) can enhance the biofilm resistance of 3D printed clear aligners while maintaining high fidelity to optical translucency and constituent mechanical properties.

Transdermal delivery of elastin peptide assisted by betaine-based deep eutectic solvent to ameliorate skin photoaging.

The unique amino acid composition of elastin peptide (EP) makes it an excellent resource to obtain antioxidant peptides. It exhibits high elastase inhibitory activity with the potential to resist skin aging and is currently used in a many cosmetic products. However, the inherent low permeability of the skin limits its ability to penetrate the skin. To address this issue, a deep eutectic solvent (SAB) with excellent bioactivity was synthesized from betaine and succinic acid and used as a permeation enhancer to improve the absorption and utilization of EP in this paper. The results showed that low SAB concentrations significantly increased the transdermal delivery of EP. The 3D epidermal skin model (EpiKutis®) demonstrated that SAB/EP induced the synthesis of hyaluronic acid (HA) and filaggrin (FLG), accelerated skin barrier repair, and reduced water loss. Additionally, the zebrafish embryonic model showed that SAB/EP could reduce melanin secretion, decrease melanin deposition, and have an ameliorative effect on skin photoaging. Cellular experiments proved that SAB/EP can stimulate human skin fibroblasts to secrete procollagen I and elastin, improving skin elasticity and anti-wrinkle. The combination of EP and DES is a new attempt that is expected to be used as a safe and effective anti-wrinkle cosmetic material.

Structural insights into the molecular effects of the anthelmintics monepantel and betaine on the Caenorhabditis elegans acetylcholine receptor ACR-23.

Anthelmintics are drugs used for controlling pathogenic helminths in animals and plants. The natural compound betaine and the recently developed synthetic compound monepantel are both anthelmintics that target the acetylcholine receptor ACR-23 and its homologs in nematodes. Here, we present cryo-electron microscopy structures of ACR-23 in apo, betaine-bound, and betaine- and monepantel-bound states. We show that ACR-23 forms a homo-pentameric channel, similar to some other pentameric ligand-gated ion channels (pLGICs). While betaine molecules are bound to the classical neurotransmitter sites in the inter-subunit interfaces in the extracellular domain, monepantel molecules are bound to allosteric sites formed in the inter-subunit interfaces in the transmembrane domain of the receptor. Although the pore remains closed in betaine-bound state, monepantel binding results in an open channel by wedging into the cleft between the transmembrane domains of two neighboring subunits, which causes dilation of the ion conduction pore. By combining structural analyses with site-directed mutagenesis, electrophysiology and in vivo locomotion assays, we provide insights into the mechanism of action of the anthelmintics monepantel and betaine.

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.

Unveiling the crucial role of betaine: modulation of GABA homeostasis via SLC6A1 transporter (GAT1).

Betaine is an endogenous osmolyte that exhibits therapeutic potential by mitigating various neurological disorders. However, the underlying cellular and molecular mechanisms responsible for its neuroprotective effects remain puzzling.In this study, we describe a possible mechanism behind the positive impact of betaine in preserving neurons from excitotoxicity. Here we demonstrate that betaine at low concentration modulates the GABA uptake by GAT1 (slc6a1), the predominant GABA transporter in the central nervous system. This modulation occurs through the temporal inhibition of the transporter, wherein prolonged occupancy by betaine impedes the swift transition of the transporter to the inward conformation. Importantly, the modulatory effect of betaine on GAT1 is reversible, as the blocking of GAT1 disappears with increased extracellular GABA. Using electrophysiology, mass spectroscopy, radiolabelled cellular assay, and molecular dynamics simulation we demonstrate that betaine has a dual role in GAT1: at mM concentration acts as a slow substrate, and at µM as a temporal blocker of GABA, when it is below its K0.5. Given this unique modulatory characteristic and lack of any harmful side effects, betaine emerges as a promising neuromodulator of the inhibitory pathways improving GABA homeostasis via GAT1, thereby conferring neuroprotection against excitotoxicity.

Betaine ameliorates arsenic-induced kidney injury in mice by mitigating oxidative stress-mediated inflammation.

Arsenic, an environmental pollutant and poisonous metalloid, has adverse effects on different body organs, including the kidneys. Betaine is a natural nutrient that has many beneficial health effects. This research was conducted to examine the impact of betaine on nephrotoxicity caused by inorganic arsenic (NaAsO2) in mice. Mice were separated into following groups: control, NaAsO2 (50 ppm), NaAsO2 (50 ppm) + betaine (500 mg/kg), and betaine (500 mg/kg). Mice were received NaAsO2 via drinking water for 8 consecutive weeks and betaine was given to the animals via gavage once daily in the 7th and 8th weeks of the study. Upon completion of the study, the mice were euthanized and samples of serum and kidney were obtained for further evaluations. Administration of NaAsO2 increased the levels of blood urea nitrogen and creatinine in the serum. It enhanced the amounts of renal malondialdehyde and decreased the total thiol levels, as well as the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase). Furthermore, it enhanced the levels of renal inflammatory indicators (tumor necrosis factor-alpha and nitric oxide). Western blot results exhibited an increase in the protein expression of nuclear factor kappa B (NF-κB), and phosphorylated NF-κB in NaAsO2-treated mice. Histopathological results also confirmed kidney damage caused by NaAsO2. However, treatment with betaine improved NaAsO2-related kidney injuries in mice. The results of this work indicated that betaine can attenuate kidney damage caused by NaAsO2 by inhibiting oxidative stress and inflammation.

Self-assembled thymol-betaine co-crystals with controlled release and hygroscopic properties as green preservatives for aflatoxin prevention.

Mycotoxins are representative contaminants causing food losses and food safety problems worldwide. Thymol can effectively inhibit pathogen infestation and aflatoxin accumulation during grain storage, but high volatility limits its application. Here, a thymol-betaine co-crystal system was synthesized through grinding-induced self-assembly. The THY-TMG co-crystal exhibited excellent thermal stability with melting point of 91.2 °C owing to abundant intermolecular interactions. Remarkably, after 15 days at 30 °C, the release rate of thymol from co-crystal was only 55%, far surpassing that of pure thymol. Notably, the co-crystal demonstrated the ability to bind H2O in the environment while controlling the release of thymol, essentially acting as a desiccant. Moreover, the co-crystals effectively inhibited the growth of Aspergillus flavus and the biosynthesis of aflatoxin B1. In practical terms, the THY-TMG co-crystal was successful in preventing AFB1 contamination and nutrients loss in peanuts, thereby prolonging their shelf-life under conditions of 28 °C and 70% RH.

Effect of dietary treatments on performance, oocysts shedding and lesion scores in broiler chickens experimentally challenged with Eimeria infection.

Although anticoccidials effectively control coccidiosis, a needed reduction in the reliance on antimicrobials in animal production leads to the exploration of alternative compounds. The present study aimed to test five different dietary treatments to counteract the negative impact of coccidiosis on broiler chickens' health and performance. 1-day-old male Ross 308 broilers (n = 960) were randomly assigned to one of eight treatments, with six cages per treatment (20 birds/cage). To the diet of the broiler chickens of treatments (Trt) 1-5, a synbiotic was added from d0-10. From d10-28, birds of Trt1 and Trt2 were fed synbiotics, whereas birds of Trt3 were fed diets with glutamine, and birds of Trt4 and Trt5 were fed diets with a combination of ß-glucans and betaine. From d28-35 onwards, birds of Trt1 were fed a diet with a synbiotic, whereas birds of Trt2-4 received diets with glutamine, and birds of Trt5 were fed a non-supplemented diet. Birds of the positive control group (PC; Trt6) were fed a standard diet supplemented with an anticoccidial (Decoquinate). The challenged negative control (NCchall; Trt7) and non-challenged negative control (NC) Trt8 were fed a standard diet without anticoccidial or other dietary treatment. At 7 days (d) of age, all birds were inoculated with 1 023, 115, and 512 sporulated oocysts of E. acervulina, E. maxima, and E. tenella, respectively, except for Trt8. Body weight gain (BWG), feed intake, and feed conversion ratio were assessed for each feeding phase (d0-10, d10-28 and d28-35) and overall experimental period (d0-35). Oocyst shedding, Eimeria lesion scores, cecal length, and relative weight were assessed at d13, d22, d28 and d35. Additionally, oocyst shedding was determined at d9 and d17. Litter quality was evaluated at d27 and d34, and footpad lesions at d34. During the starter (d0-10) and finisher (d28-35) periods, performance did not differ between the treatments. During the grower period (d10-28), Trt6 (PC) and Trt8 (NC) chickens had the highest BWG of all treatments (P < 0.001). Dietary treatment had no effect on litter quality and severity of footpad lesions. In the PC group (Trt6), low oocyst excretion and lesion scores were found. When comparing Trt1-5 with NCchall (Trt7), none of the treatments significantly reduced oocyst output or lesion scores. In conclusion, in this experiment, none of the dietary treatments performed similar or better compared to the PC group (Trt6) regarding performance or reducing Eimeria oocyst shedding or lesion scores.

Mechanical-Enhanced and Durable Zwitterionic Hydrogel Coating for Inhibiting Coagulation and Reducing Bacterial Infection.

Blood-contact medical devices are indispensable for clinical interventions, yet their susceptibility to thrombosis and bacterial infections poses substantial risks to treatment efficacy and patient well-being. This study introduces a polysulfobetaine/alginate-CuII (SAC) zwitterionic hydrogel coating on polyurethane (PU) surfaces. This approach retains the superhydrophilic and antifouling nature of pSBMA while conferring the antibacterial effects of copper ions. Meanwhile, the copper alginate network intertwines with the polysulfobetaine (pSBMA) network, enhancing its mechanical properties and overcoming inherent weaknesses, thereby improving coating durability. Compared to the substrate, the SAC hydrogel coating significantly reduces thrombus adhesion mass by approximately 81.5% during extracorporeal blood circulation and effectively prevents bacterial biofilm formation even in a high-concentration bacterial milieu over 30 days. Moreover, the results from an isolated blood circulation model in New Zealand white rabbits affirm the impressive anticoagulant efficacy of the SAC hydrogel coating. The findings suggest that this hydrogel coating and its application method hold promise as a solution for blood-contact material surface modification to address thrombosis and bacterial biofilm formation simultaneously.

The Unprecedented Biodegradable Polyzwitterion: A Removal-Free Patch for Accelerating Infected Diabetic Wound Healing.

Zwitterionic polymers have emerged as an important class of biomaterials to construct wound dressings and antifouling coatings over the past decade due to their excellent hydrophilicity. However, all the reported zwitterionic polymers as wound dressings are nondegradable because of noncleavable carbon─carbon bonding backbones, and must be removed periodically after treatment to avoid hypoxia in the wound, thus leading to potential secondary injury. In this work, a biodegradable polyzwitterion patch is fabricated for the first time by ring-opening polymerization of carboxybetaine dithiolane (CBDS), which is self-crosslinked via inter-amide hydrogen bonds and zwitterionic dipole-dipole interactions on the side chains. The unprecedented polyCBDS (PCBDS) patch demonstrates enough ductility owing to the intermolecular physical interactions to fully cover irregular wounds, also showing excellent biodegradability and antifouling performance resulted from the existence of disulfide bonds and carboxybetaine groups. Besides, the PCBDS degradation-induced released CBDS owns potent antioxidant and antibacterial activities. This PCBDS patch is used as a diabetic wound dressing, inhibiting bacterial adhesion on the external surface, and its degradation products can exactly kill bacteria and scavenge excessive reactive oxygen species (ROS) at the wound site to regulate local microenvironment, including regulation of cytokine express and macrophage polarization, accelerating infected diabetic wound repair, and also avoiding the potential secondary injury.

Exploring Seaweed and Glycine Betaine Biostimulants for Enhanced Phenolic Content, Antioxidant Properties, and Gene Expression of Vitis vinifera cv. "Touriga Franca" Berries.

Climate change will pose a challenge for the winemaking sector worldwide, bringing progressively drier and warmer conditions and increasing the frequency and intensity of weather extremes. The short-term adaptation strategy of applying biostimulants through foliar application serves as a crucial measure in mitigating the detrimental effects of environmental stresses on grapevine yield and berry quality. The aim of this study was to evaluate the effect of foliar application of a seaweed-based biostimulant (A. nodosum-ANE) and glycine betaine (GB) on berry quality, phenolic compounds, and antioxidant activity and to elucidate their action on the secondary metabolism. A trial was installed in a commercial vineyard (cv. "Touriga Franca") in the Cima Corgo (Upper Corgo) sub-region of the Douro Demarcated Region, Portugal. A total of four foliar sprayings were performed during the growing season: at flowering, pea size, bunch closer, and veraison. There was a positive effect of GB in the berry quality traits. Both ANE and GB increased the synthesis of anthocyanins and other phenolics in berries and influenced the expression of genes related to the synthesis and transport of anthocyanins (CHS, F3H, UFGT, and GST). So, they have the potential to act as elicitors of the secondary metabolism, leading to improved grape quality, and also to set the foundation for sustainable agricultural practices in the long run.

Green Extraction of Depsidones and Depsides from Hypogymnia physodes (L.) Nyl. Using Natural Deep Eutectic Solvents.

Various studies have shown that Hypogymnia physodes are a source of many biologically active compounds, including lichen acids. These lichen-specific compounds are characterized by antioxidant, antiproliferative, and antimicrobial properties, and they can be used in the cosmetic and pharmaceutical industries. The main aim of this study was to optimize the composition of natural deep eutectic solvents based on proline or betaine and lactic acid for the extraction of metabolites from H. physodes. The design of the experimental method and the response surface approach allowed the optimization of the extraction process of specific lichen metabolites. Based on preliminary research, a multivariate model of the experiment was developed. For optimization, the following parameters were employed in the experiment to confirm the model: a proline/lactic acid/water molar ratio of 1:2:2. Such a mixture allowed the efficient extraction of three depsidones (i.e., physodic acid, physodalic acid, 3-hydroyphysodic acid) and one depside (i.e., atranorin). The developed composition of the solvent mixtures ensured good efficiency when extracting the metabolites from the thallus of H. physodes with high antioxidant properties.

Betaine alleviates spermatogenic cells apoptosis of oligoasthenozoospermia rat model by up-regulating methyltransferases and affecting DNA methylation.

BACKGROUND: Oligoasthenozoospermia is the most common type of semen abnormality in male infertile patients. Betaine (BET) has been proved to have pharmacological effects on improving semen quality. BET also belongs to endogenous physiological active substances in the testis. However, the physiological function of BET in rat testis and its pharmacological mechanism against oligoasthenozoospermia remain unclear. PURPOSE: This research aims to prove the therapeutic effect and potential mechanism of BET on oligoasthenozoospermia rat model induced by Tripterygium wilfordii glycosides (TWGs). METHODS: The oligoasthenozoospermia rat model was established by a continuous gavage of TWGs (60 mg/kg) for 28 days. Negative control group, oligoasthenozoospermia group, positive drug group (levocarnitine, 300 mg/kg), and 200 mg/kg, 400 mg/kg, and 800 mg/kg BET groups were created for exploring the therapeutic effect of BET on the oligoasthenozoospermia rat model. The therapeutic effect was evaluated by HE and TUNEL staining. Immunofluorescence assay of DNMT3A, PIWIL1, PRMT5, SETDB1, BHMT2, and METTL3, methylation capture sequencing, Pi-RNA sequencing, and molecular docking were used to elucidate potential pharmacological mechanisms. RESULTS: It is proved that BET can significantly restore testicular pathological damage induced by TWGs, which also can significantly reverse the apoptosis of spermatogenic cells. The spermatogenic cell protein expression levels of DNMT3A, PIWIL1, PRMT5, SETDB1, BHMT2, and METTL3 significantly decreased in oligoasthenozoospermia group. 400 mg/kg and 800 mg/kg BET groups can significantly increase expression level of the above-mentioned proteins. Methylation capture sequencing showed that BET can significantly increase the 5mC methylation level of Spata, Spag, and Specc spermatogenesis-related genes. Pi-RNA sequencing proved that the above-mentioned genes produce a large number of Pi-RNA under BET intervention. Pi-RNA can form complexes with PIWI proteins to participate in DNA methylation of target genes. Molecular docking indicated that BET may not directly act as substrate for methyltransferase and instead participates in DNA methylation by promoting the methionine cycle and increasing S-adenosylmethionine synthesis. CONCLUSION: BET has a significant therapeutic effect on oligoasthenozoospermia rat model induced by TWPs. The mechanism mainly involves that BET can increase the methylation level of Spata, Specc, and Spag target genes through the PIWI/Pi-RNA pathway and up-regulation of methyltransferases (including DNA methyltransferases and histone methyltransferases).