Alzheimer's disease (AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progression are currently unavailable, a plethora of studies have highlighted the potential advantages of exercise rehabilitation for managing this condition. Those studies show that exercise rehabilitation can enhance cognitive function and improve the quality of life for individuals affected by AD. Therefore, exercise rehabilitation has been regarded as one of the most important strategies for managing patients with AD. Herein, we provide a comprehensive analysis of the currently available findings on exercise rehabilitation in patients with AD, with a focus on the exercise types which have shown efficacy when implemented alone or combined with other treatment methods, as well as the potential mechanisms underlying these positive effects. Specifically, we explain how exercise may improve the brain microenvironment and neuronal plasticity. In conclusion, exercise is a cost-effective intervention to enhance cognitive performance and improve quality of life in patients with mild to moderate cognitive dysfunction. Therefore, it can potentially become both a physical activity and a tailored intervention. This review may aid the development of more effective and individualized treatment strategies to address the challenges imposed by this debilitating disease, especially in low- and middle-income countries.

JOURNAL/nrgr/04.03/01300535-202410000-00024/figure1/v/2024-02-06T055622Z/r/image-tiff Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.

JOURNAL/nrgr/04.03/01300535-202410000-00031/figure1/v/2024-02-06T055622Z/r/image-tiff Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogen-activated protein kinase (MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.

The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.

JOURNAL/nrgr/04.03/01300535-202410000-00029/figure1/v/2024-02-06T055622Z/r/image-tiff Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1 (APP/PS1). Here, we performed 16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-L-threonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesium-L-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins (zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

JOURNAL/nrgr/04.03/01300535-202410000-00027/figure1/v/2024-02-06T055622Z/r/image-tiff Spinal cord injury is a disabling condition with limited treatment options. Multiple studies have provided evidence suggesting that small extracellular vesicles (SEVs) secreted by bone marrow mesenchymal stem cells (MSCs) help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury. Strikingly, hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs (HSEVs) exhibit increased therapeutic potency. We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair. SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation. HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation. HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro. MicroRNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that miR-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1. Reducing miR-146a-5p expression in HSEVs partially attenuated macrophage polarization. Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting miR-146a-5p, which alters macrophage polarization. This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202410000-00026/figure1/v/2024-02-06T055622Z/r/image-tiff Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.

It has been reported both in clinic and rodent models that beyond spinal cord injury directly induced symptoms, such as paralysis, neuropathic pain, bladder/bowel dysfunction, and loss of sexual function, there are a variety of secondary complications, including memory loss, cognitive decline, depression, and Alzheimer's disease. The large-scale longitudinal population-based studies indicate that post-trauma depression is highly prevalent in spinal cord injury patients. Yet, few basic studies have been conducted to address the potential molecular mechanisms. One of possible factors underlying the depression is the reduction of adult hippocampal neurogenesis which may come from less physical activity, social isolation, chronic pain, and elevated neuroinflammation after spinal cord injury. However, there is no clear consensus yet. In this review, we will first summarize the alteration of hippocampal neurogenesis post-spinal cord injury. Then, we will discuss possible mechanisms underlie this important spinal cord injury consequence. Finally, we will outline the potential therapeutic options aimed at enhancing hippocampal neurogenesis to ameliorate depression.

Metabolism is a fundamental process by which biochemicals are broken down to produce energy (catabolism) or used to build macromolecules (anabolism). Metabolism has received renewed attention as a mechanism that generates molecules that modulate multiple cellular responses. This was first identified in cancer cells as the Warburg effect, but it is also present in immunocompetent cells. Studies have revealed a bidirectional influence of cellular metabolism and immune cell function, highlighting the significance of metabolic reprogramming in immune cell activation and effector functions. Metabolic processes such as glycolysis, oxidative phosphorylation, and fatty acid oxidation have been shown to undergo dynamic changes during immune cell response, facilitating the energetic and biosynthetic demands. This review aims to provide a better understanding of the metabolic reprogramming that occurs in different immune cells upon activation, with a special focus on central nervous system disorders. Understanding the metabolic changes of the immune response not only provides insights into the fundamental mechanisms that regulate immune cell function but also opens new approaches for therapeutic strategies aimed at manipulating the immune system.

This comprehensive review explores the intricate relationship between nutrition, the gut microbiome, steroid hormones, and Parkinson's disease within the context of the gut-brain axis. The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease, encompassing diverse components such as the gut microbiota, immune system, metabolism, and neural pathways. The gut microbiome, profoundly influenced by dietary factors, emerges as a key player. Nutrition during the first 1000 days of life shapes the gut microbiota composition, influencing immune responses and impacting both child development and adult health. High-fat, high-sugar diets can disrupt this delicate balance, contributing to inflammation and immune dysfunction. Exploring nutritional strategies, the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk. Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders. Beyond nutrition, emerging research uncovers potential interactions between steroid hormones, nutrition, and Parkinson's disease. Progesterone, with its anti-inflammatory properties and presence in the nervous system, offers a novel option for Parkinson's disease therapy. Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects. The review addresses the hypothesis that α-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve. Gastrointestinal symptoms preceding motor symptoms support this hypothesis. Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances, emphasizing the potential of microbiota-based interventions. In summary, this review uncovers the complex web of interactions between nutrition, the gut microbiome, steroid hormones, and Parkinson's disease within the gut-brain axis framework. Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.

JOURNAL/nrgr/04.03/01300535-202410000-00030/figure1/v/2024-02-06T055622Z/r/image-tiff Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum (L. barbarum) polysaccharide (LBP) protects degenerated photoreceptors in rd1, a transgenic mouse model of retinitis pigmentosa. L. barbarum glycopeptide (LbGP) is an immunoreactive glycoprotein extracted from LBP. In this study, we investigated the potential protective effect of LbGP on a chemically induced photoreceptor-degenerative mouse model. Wild-type mice received the following: oral administration of LbGP as a protective pre-treatment on days 1-7; intraperitoneal administration of 40 mg/kg N-methyl-N-nitrosourea to induce photoreceptor injury on day 7; and continuation of orally administered LbGP on days 8-14. Treatment with LbGP increased photoreceptor survival and improved the structure of photoreceptors, retinal photoresponse, and visual behaviors of mice with photoreceptor degeneration. LbGP was also found to partially inhibit the activation of microglia in N-methyl-N-nitrosourea-injured retinas and significantly decreased the expression of two pro-inflammatory cytokines. In conclusion, LbGP effectively slowed the rate of photoreceptor degeneration in N-methyl-N-nitrosourea-injured mice, possibly through an anti-inflammatory mechanism, and has potential as a candidate drug for the clinical treatment of photoreceptor degeneration.

Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

JOURNAL/nrgr/04.03/01300535-202410000-00032/figure1/v/2024-02-06T055622Z/r/image-tiff Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries--the United States, China, Japan, the United Kingdom, Spain, Germany, and France--by searching for all global diabetic eye disease journal articles in the Web of Science and PubMed databases, all global registered clinical trials in the ClinicalTrials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority (89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema (9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development (58.19%). Approximately half of the trials (49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic (40 out of 1830; 2.19%) and diabetic eye disease (3 out of 1830; 0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.

JOURNAL/nrgr/04.03/01300535-202410000-00025/figure1/v/2024-02-06T055622Z/r/image-tiff In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1 (PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.eB-GFAP-shPTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-shPTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.

JOURNAL/nrgr/04.03/01300535-202410000-00028/figure1/v/2024-02-06T055622Z/r/image-tiff Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome. 3'-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3'-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3'-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3'-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3'-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3'-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3'-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3'-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia (leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.

In this study, the ultrasonic-microwave pretreatment was defined as a processing technology in the production of tribute citrus powder, and it could increase the flavonoid compounds in the processing fruit powder. A total of 183 upregulated metabolites and 280 downregulated metabolites were obtained by non-targeted metabolomics, and the differential metabolites was mainly involved in the pathways of flavonoid biosynthesis, flavone and flavonol biosynthesis. A total of 8 flavonoid differential metabolites were obtained including 5 upregulated metabolites (6"-O-acetylglycitin, scutellarin, isosakuranin, rutin, and robinin), and 3 downregulated metabolites (astragalin, luteolin, and (-)-catechin gallate) by flavonoids-targeted metabolomics. The 8 flavonoid differential metabolites participated in the flavonoid biosynthesis pathways, flavone and flavonol biosynthesis pathways, and isoflavonoid biosynthesis pathways. The results provide a reference for further understanding the relationship between food processing and food components, and also lay a basis for the development of food targeted-processing technologies.

Phytosterol esters (PEs) and diacylglycerols (DAGs) have various health benefits in humans. In this study, PEs and DAGs were synthesized by lipase-catalyzed transesterification between a natural oil and phytosterols. First, commercial lipases were screened for transesterification and were further verified using multiple-ligand molecular docking. AYS "Amano" (a lipase from Candida rugosa) was found to be the optimum lipase. Subsequently, the enzymatic transesterification conditions were optimized. The optimized conditions were determined to be a 1:2 M ratio of phytosterols to oil, 100 mmol/L phytosterols, and 9 % AYS "Amano", and 50 °C for 24 h in 20 mL n-hexane. Under these conditions, over 70 % of phytosterols were converted to PEs. In this study, an efficient enzymatic process was developed to produce value-added functional oils rich in PEs and DAGs, with PEs content ≥ 31.6 %, DAGs content ≥ 11.2 %, acid value ≤ 0.91 mg KOH/g, and peroxide value ≤ 2.38 mmol/kg.

Carbonyl compounds are vital constituents that contribute to the flavor profile of alcoholic beverages. We examined 3-nitrophenylhydrazine as a derivatizing reagent for the measurement of 34 carbonyl compounds using UPLC-MS/MS. Adding formic acid and sodium acetate to the mobile phase significantly enhanced the detection limit of carbonyl compounds. The technique exhibited a notable extraction efficiency, yielding recovery percentages ranging from 83.6% to 117.1%, coupled with exceptional sensitivity, as evidenced by detection limits spanning from 0.07 μg/L to 4.80 μg/L. The relative standard deviation was <6.9%, indicating the precision and reliability of the analytical methodology. The method was verified by analyzing carbonyl compounds from red-fleshed kiwifruit wine. Furthermore, sensory assessment revealed that the amalgamation of tartaric acid, malic acid, and citric acid contributes to sour taste perception at sub-threshold concentrations through an additive interaction with supra-threshold non-volatile organic acids such as lactic acid and acetic acid.

We have developed a rapid, facile liquid crystal (LC)-based aptasensor for E. coli detection in water and juice samples. A textile grid-anchored LC platform was used with specific aptamers adsorbed via a cationic surfactant, cetyltrimethylammonium bromide (CTAB), on the LC surface. The presence of E. coli dissociates the aptamers from CTAB and restores the dark signal induced by the surfactant. Using polarized microscopy, the images of the LCs in the presence of various concentrations of E. coli were captured and analyzed using image analysis and machine learning (ML). The artificial neural networks (ANN) and extreme gradient boosting (XGBoost) rendered the best results for water samples (R2 = 0.986 and RMSE = 0.209) and juice samples (R2 = 0.976 and RMSE = 0.262), respectively. The platform was able to detect E. coli with a detection limit (LOD) of 6 CFU mL-1.

Chloramphenicol (CAP) is known to be harmful to the environment and food, posing a threat to human health. Developing an effective and convenient method for detecting CAP is crucial. An electrochemiluminescence (ECL) biosensor has been designed for sensitive detection of CAP. The improved ECL behavior was attributed to the synergistic effect of N and P co-doped Ti3C2-Apt1 (N, P-Ti3C2-Apt1) nanoprobes and high intensity focused ultrasound (HIFU) pretreatment. The doping of N and P could improve the electrochemical performance of Ti3C2. HIFU pretreatment generated more reactive oxygen species (ROS) in the luminol-O2 system. N, P-Ti3C2 could aggregate and catalyze ROS, causing an increase in ECL intensity. Furthermore, N, P-Ti3C2 as a carrier loaded more aptamer, which could recognize CAP with high specificity. The detection limit was 0.01 ng/mL. This biosensor has been successfully applied in milk and environmental water samples, highlighting its potential in the field of food and environmental analysis.

Glucosinolates (GLs) are important precursors of anticancer isothiocyanates in cruciferous plants. However, GLs in aqueous solution have been found to decompose under certain conditions, and the effect of metal ions remains unclear. In this study, high-purity glucoraphanin and glucoraphenin were used to explore the effects of metal ions with thermal treatment. The degree of GLs decomposition was affected by the type and concentration of metal ions, temperature, and duration of heating. Fe3+ (1 mM) was found to cause the decomposition of 78.1 % of glucoraphanin and 94.7 % of glucoraphenin in 12 h at 100 °C, while Cu2+ completely decomposed both GLs. The decomposition products were all the corresponding nitriles, and decomposition dynamic curves were first-order. In addition to accelerating hydrolysis, metal ions may promote the generation of nitriles as catalysts. The exploration of GLs decomposition could help to adopt more effective methods to avoid the formation of toxic compounds.

This study aimed to investigate the interaction between L.casei and L.bulgaricus with Polygonatum sibiricum saponins (PSS) and to explore the co-microencapsulation to reduce their loss rate during storage and consumption. 1% PSS was added to the culture broth, and it was found that the growth and metabolism of the strains were accelerated, especially in the compound probiotic group, indicating that PSS has potential for prebiotics. LC-MS observed significant differences in the composition and content of saponins in PSS. The metabolomics results suggest that the addition of PSS resulted in significant changes in the metabolites of probiotics. In addition, it was found that the combination of probiotics and PSS may have stronger hypoglycemic ability (ɑ-glucosidase, HepG2). Finally, a co-microencapsulated delivery system was constructed using zein and isomaltooligosaccharide. This system can achieve more excellent resistance of probiotics and PSS in gastrointestinal fluids, effectively transporting both to the small intestine.

This paper presents a comprehensive study of commercially available monovarietal red and white wines from Fruška Gora mountain in Serbia, conducted to characterize their chemical and biochemical properties. Namely, 72 wines of 18 different Vitis vinifera varieties, including international, domestic and autochthonous ones, were assessed. Phenolic profile of wines was determined qualitatively, using spectrophotometric methods, and quantitatively, using LC-MS/MS and HPLC-UV/VIS methods. Quantified phenolic compounds pointed out differences between red and white wines, where some compounds stood out as distinctive characteristic of analyzed varieties, while others served as chemotaxonomic markers of the Fruška Gora region. Antioxidant and inhibitory properties towards acetylcholinesterase were evaluated for all wines and their relation to phenolic composition was investigated. This study is valuable since chemical and biochemical properties of domestic and autochthonous Fruška Gora varieties are reported for the first time. Also, international varieties studied herein gave distinctive information about the terroir of Fruška Gora region, which is scarce in scientific literature.

The duration of storage significantly influences the quality and market value of Qingzhuan tea (QZT). Herein, a high-resolution multiple reaction monitoring (MRMHR) quantitative method for markers of QZT storage year was developed. Quantitative data alongside multivariate analysis were employed to discriminate and predict the storage year of QZT. Furthermore, the content of the main biochemical ingredients, catechins and alkaloids, and free amino acids (FAA) were assessed for this purpose. The results show that targeted marker-based models exhibited superior discrimination and prediction performance among four datasets. The R2Xcum, R2Ycum and Q2cum of orthogonal projection to latent structure-discriminant analysis discrimination model were close to 1. The correlation coefficient (R2) and the root mean square error of prediction of the QZT storage year prediction model were 0.9906 and 0.63, respectively. This study provides valuable insights into tea storage quality and highlights the potential application of targeted markers in food quality evaluation.

The infrared spectroscopy (IR) signal of protein is prone to being covered by impurity signals, and the accuracy of the secondary structure content calculated using spectral data is poor. To tackle this challenge, a rapid high-precision quantitative model for protein secondary structure was proposed. Firstly, a two-dimensional correlation calculation was performed based on 60 groups of soybean protein isolates (SPI) infrared spectroscopy data, resulting in a two-dimensional correlation infrared spectroscopy (2DCOS-IR). Subsequently, the optimal characteristic bands of the four secondary structures were extracted from the 2DCOS-IR. Ultimately, partial least squares (PLS), long short-term memory (LSTM), and bidirectional long short-term memory (BILSTM) algorithms were used to model the extracted characteristic bands and predict the content of SPI secondary structure. The findings suggested that BILSTM combined with 2DCOS-IR model (2DCOS-BILSTM) exhibited superior predictive performance. The prediction sets for α-helix, β-sheet, β-turn, and random coil were designated as 0.9257, 0.9077, 0.9476, and 0.8443, respectively, and their corresponding RMSEP values were 0.26, 0.48, 0.20, and 0.15. This strategy enhances the precision of IR and facilitates the rapid identification of secondary structure components within SPI, which is vital for the advancement of protein industrial production.

Heme proteins and their derivatives play important roles in inducing lipid oxidation to produce volatile compounds during bacon drying. This study investigated the effects of heme proteins and their derivatives (hemoglobin, myoglobin, nitrosylmyoglobin, hemin, Fe2+, and Fe3+) on lipid and volatiles profiles in the washed pig muscle (WPM) model. The results of the study indicated that the inducers primarily caused the oxidation of glycerophospholipids. Furthermore, hemoglobin and myoglobin had the most significant impact, and their potential substrates may include PE (O-18:2/20:4), PE (O-18:1/20:4), PC (16:0/18:1), and PE (O-18:2/18:2). Nitrosomyoglobin has limited ability to promote lipid oxidation and may protect ether phospholipids from oxidation. The analysis of the volatiles in the model revealed that heme proteins and their derivatives have the ability to induce the production of key aroma compounds. The descending order of effectiveness in inducing the production of aroma compounds is as follows: hemoglobin, myoglobin, hemin, and nitrosylmyoglobin. The effectiveness of Fe2+ and Fe3+ is similar to that of nitrosylmyoglobin.

This article summarizes the characterization, by shotgun proteomics, of 11 bacterial strains identified as responsible for seafood spoilage. A total of 4455 peptide spectrum matches, corresponding to 4299 peptides and 3817 proteins were identified. Analyses of data determined the functional pathways they are involved in. The proteins identified were integrated into a protein-protein network that involves 371 nodes and 3016 edges. Those proteins are implicated in energy pathways, peptidoglycan biosynthesis, spermidine/putrescine metabolism. An additional 773 peptides were characterized as virulence factors, that participates in bacterial pathogenesis; while 14 peptides were defined as biomarkers, as they can be used to differentiate the bacterial species present. This report represents the most extensive proteomic repository available in the field of seafood spoilage bacteria; the data substantially advances the understanding of seafood decay, as well as provides fundamental bases for the recognition of the bacteria existent in seafood that cause spoilage during food processing/storage.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), a type of fatty acid that has many health benefits, are of increasing concern. Herein, we developed a method for the rapid esterification and enrichment of ω-3 PUFAs in eggs, which includes microwave-assisted esterification (MAE) and electrically enhanced solid-phase microextraction (EE-SPME). Combined with gas chromatographic, efficient detection of ω-3 PUFAs was achieved in eggs. Under microwave radiation, the esterification efficiency exhibited a significant increase ranging from 5.06 to 10.65 times. The EE-SPME method reduced extraction time from 50 to 15 min. In addition, improvements in extractive fiber coating materials were explored, which ensured efficient extraction of ω-3 PUFAs. Under the optimal conditions, the method displayed a low detection limit (1.01-1.54 μg L-1), good recoveries (85.82%-106.01%), and wide linear range (7.5-1000 μg L-1), which was successfully applied to determine ω-3 PUFAs in real egg samples.

β-galactosidase (lactase) is commercially important as a dietary supplement to alleviate the symptoms of lactose intolerance. This work investigated a unique activation of CMP (carboxymethylated (1 → 3)-β-d-glucan) on lactase and its mechanism by comparing it with carboxymethyl chitosan (CMCS), an inhibitor of lactase. The results illustrated that the secondary and tertiary structures of lactase were altered and its active sites exposed after complexation with CMP, and dissociation of lactase aggregates was also observed. These changes favored better accessibility of the substrate to the active sites of lactase, resulting in a maximum increase of 60.5 % in lactase activity. Furthermore, the hydrophobic and electrostatic interactions with lactase caused by the carboxymethyl group of CMP were shown to be crucial for its activation ability. Thus, the improvement of lactase activity and stability by CMP shown here is important for the development of new products in the food and pharmaceutical industries.

Baked oyster is a popular seafood dish around the world. The present study investigated the effect of various concentrations of a green-tea extract (GTE) marinade on the safety and sensory profiles of oysters baked for different durations. The results showed 10 g/L of GTE and 10-min baking time was the optimal combination, as supported by significantly attenuated lipid oxidation (35.29 %) and Nε-(carboxyethyl)lysine (CEL) content (48.51 %) without appreciable negative impact on the sensory or nutritional quality of the oysters. However, high concentrations of the marinade or prolonged baking promoted protein oxidation and Nε-(carboxymethyl)lysine (CML) formation likely through the pro-oxidative action of the GTE phytochemicals. Correlation analysis further revealed the main factors that affected CML, CEL, and fluorescent AGEs generation, respectively. These findings provide theoretical support for the protective effect and mechanism of GTE against quality deterioration of baked oysters and would help broaden the application of GTE in the food industry.

Buffalo colostrum is the initial mammary secretion after parturition, consisting of nutritional and bioactive components. In this study, we conducted a proteomic analysis of buffalo colostrum whey to identify bioactive proteins and peptides. A total of 107 differentially expressed proteins (DEPs) were identified in buffalo colostrum whey compared to those in mature milk. Gene Ontology analysis revealed that DEPs were primarily associated with immune response and tissue development. KEGG pathway enrichment suggested that colostrum actively enhances nascent immunity involved in interleukin and interferon signaling pathways. Furthermore, candidate antimicrobial peptides (AMPs) of whey protein hydrolysates from buffalo colostrum were characterized, which exhibits broad-spectrum activity against gram-positive and gram-negative pathogens. Overall, this study improves our understanding of protein variations in buffalo lactation, and contributes to the development of AMPs from buffalo colostrum.

C-Phycocyanin and sugar (C-PC/S) blended agar hydrocolloid was prepared and its rheological, thermo-functional and morphological properties were examined based on the fluorescence excitation-emission matrix profile. Sucrose (40%, w/v) determined as a superior preservative, maintaining the native conformation of C-PC effectively. C-PC/S exhibited enhanced structural integrity with high storage modulus (G') and 86.4% swelling index. FT-IR demonstrated strong intramolecular bonding. TGA revealed that the presence of sucrose prolonged the devolatilization peak up to 325 °C, with a degradation rate of -2.273 mg/min, it the thermal stability. C-PC/S fortified hydrocolloid in ice cream (5.0% w/w), reduced melting rate up to five times. In conclusion, sucrose as a promising enhancer of color stability and structural integrity for C-PC, and this combination effectively improves the functional and rheological properties. Further, the findings exposed the agar hydrocolloid as a potential enhancer of color retention and improved performance for various food and cosmetic products.

One of the main reasons for hyperuricemia is high purine intake. The primary strategy for treating hyperuricemia is blocking the purine metabolism enzyme. However, by binding the purine bases directly, we suggested a unique therapeutic strategy that might interfere with purine metabolism. There have been numerous reports of extensive interactions between proteins and purine bases. Adenine, constituting numerous protein co-factors, can interact with the adenine-binding motif. Using Bayesian Inference and Markov chain Monte Carlo sampling, we created a novel adenine-binding peptide Ile-Tyr-Val-Thr based on the structure of the adenine-binding motifs. Ile-Tyr-Val-Thr generates a semi-pocket that can clip the adenine within, as demonstrated by docking. Then, using thermodynamic techniques, the interaction between Ile-Tyr-Val-Thr and adenine was confirmed. The KD value is 1.50e-5 (ΔH = -20.2 kJ/mol and ΔG = -27.6 kJ/mol), indicating the high affinity. In brief, the adenine-binding peptide Ile-Tyr-Val-Thr may help lower uric acid level by blocking the absorption of food-derived adenine.

Legume proteins can be induced to form amyloid-like fibrils upon heating at low pH, with the exact conditions greatly impacting the fibril characteristics. The protein extraction method may also impact the resulting fibrils, although this effect has not been carefully examined. Here, the fibrillization of lentil protein prepared using various extraction methods and the corresponding fibril morphology were characterized. It was found that an acidic, rather than alkaline, protein extraction method was better suited for producing homogeneous, long, and straight fibrils from lentil proteins. During alkaline extraction, co-extracted phenolic compounds bound proteins through covalent and non-covalent interactions, contributing to the formation of heterogeneous, curly, and tangled fibrils. Recombination of isolated phenolics and proteins (from acidic extracts) at alkaline pH resulted in a distinct morphology, implicating a role for polyphenol oxidase also in modifying proteins during alkaline extraction. These results help disentangle the complex factors affecting legume protein fibrillization.

Recently, deep eutectic solvents (DES) have been extensively researched as a more biocompatible and efficient alternative to conventional solvents for extracting pigments from natural resources. The efficiency of DES extraction for the anthocyanin and carotenoid can be enhanced by microwave-assisted extraction (MAE) and/or ultrasound-assisted extraction (UAE) techniques. Apart from the extraction efficiency, the toxicity and recovery of the pigments and their bioavailability are crucial for potential applications. A plethora of studies have explored the extraction efficiency, toxicity, and recovery of pigments from various natural plant-based matrices using DES. Nevertheless, a detailed review of the deep eutectic solvent extraction of natural pigments has not been reported to date. Additionally, the toxicity, safety, and bioavailability of the extracted pigments, and their potential applications are not thoroughly documented. Therefore, this review is designed to understand the aforementioned concepts in using DES for anthocyanin and carotenoid extraction.