SKN-1 is indispensable for protection against Aß-induced proteotoxicity by a selenopeptide derived from Cordyceps militaris.

Oxidative stress (OS) and disruption of proteostasis caused by aggregated proteins are the primary causes of cell death in various diseases. Selenopeptides have shown the potential to control OS and alleviate inflammatory damage, suggesting promising therapeutic applications. However, their potential function in inhibiting proteotoxicity is not yet fully understood. To address this gap in knowledge, this study aimed to investigate the effects and underlying mechanisms of the selenopeptide VPRKL(Se)M on amyloid ß protein (Aß) toxicity in transgenic Caenorhabditis elegans. The results revealed that supplementation with VPRKL(Se)M can alleviate Aß-induced toxic effects in the transgenic C. elegans model. Moreover, the addition of VPRKL(Se)M inhibited the Aß aggregates formation, reduced the reactive oxygen species (ROS) levels, and ameliorated the overall proteostasis. Importantly, we found that the inhibitory effects of VPRKL(Se)M on Aß toxicity and activation of the unfolded protein are dependent on skinhead-1 (SKN-1). These findings suggested that VPRKL(Se)M is a potential bioactive agent for modulating SKN-1, which subsequently improves proteostasis and reduces OS. Collectively, the findings from the current study suggests VPRKL(Se)M may play a critical role in preventing protein disorder and related diseases.

Impacts of selenium enrichment on nutritive value and obesity prevention of Cordyceps militaris: A nutritional, secondary metabolite, and network pharmacological analysis.

This study aimed to compare the nutritive value and obesity prevention of ordinary Cordyceps militaris (CM) and selenium-enriched CM (SeCM). The results indicated that Se enrichment significantly increased the total carbohydrate and soluble dietary fiber content, while the protein and insoluble dietary fiber content decreased. Although the fat content was not affected, the medium and long-chain fatty acids content significantly changed. Moreover, Se enrichment significantly elevated the secondary metabolites belonging to terpenoids and alkaloids, which are linked with the enhanced biosynthesis of secondary metabolites. Both CM and SeCM reduced body weight, adipose accumulation, impaired glucose tolerance, and lipid levels in high-fat diet (HFD)-fed mice, and there was no significant difference between them. Network pharmacological analysis revealed that dietary CM and SeCM prevented HFD-induced obesity and associated metabolic diseases with multi-ingredients acting on multi-targets. Overall, Se enrichment improved the nutritive value of CM without altering its role in preventing obesity.

Comparison of Neuroprotection and Regulating Properties on Gut Microbiota between Selenopeptide Val-Pro-Arg-Lys-Leu-SeMet and Its Native Peptide Val-Pro-Arg-Lys-Leu-Met In Vitro and In Vivo.

Selenopeptides are promising candidates for intervening in neuroinflammation; however, the key role of selenium (Se) in selenopeptides remains poorly understood. To address this gap, we compared the neuroprotective effects of selenopeptide Val-Pro-Arg-Lys-Leu-SeMet (namely, Se-P1) and its native peptide Val-Pro-Arg-Lys-Leu-Met (namely, P1). Our results demonstrate that Se-P1 treatment exhibits superior antioxidant and antineuroinflammatory effects in PC12 cells and lipopolysaccharide (LPS)-injured mice compared to P1. Moreover, the administration of Se-P1 and P1 resulted in a shift in the gut microbiota composition. Notably, during LPS-induced injury, Se-P1 treatment demonstrated greater stability in maintaining gut microbiota composition compared to P1 treatment. Specifically, Se-P1 may have a positive impact on gut microbiota dysbiosis by modulating inflammatory-related bacteria such as enhancing Lactobacillus abundance while reducing that of Lachnospiraceae_NK4A136_group. Furthermore, the alteration of metabolites induced by Se-P1 treatment exhibited a significant correlation with gut microbiota, subsequently modulating the inflammatory-related metabolic pathways including histidine metabolism, lysine degradation, and purine metabolism. These findings suggest that organic Se contributes to the bioactivities of Se-P1 in mitigating neuroinflammation in LPS-injured mice compared to P1. These findings hold significant value for the development of potential preventive or therapeutic strategies against neurodegenerative diseases and introduce novel concepts in selenopeptide nutrition and supplementation recommendations.

[Effect of neuroelectrophysiological changes on the clinical manifestations and surgical outcomes of lumbar degenerative diseases].

OBJECTIVE: To evaluate the effects of electromyography on the clinical manifestations and prognosis after posterior lumbar interbody fusion(PLIF) of degenerative lumbar diseases. METHODS: A retrospective analysis was performed on 68 patients with degenerative lumbar diseases, including 29 males and 39 females, aged 21 to 84 years old, who underwent electromyogram (EMG) from January 2018 to October 2019. The patients were divided into negative and positive groups according to whether theresults of EMG was normal or abnormal, PLIF surgery was performed in both groups. The preoperative duration of illness, postoperative recovery time, operative time, intraoperative blood loss, postoperative ambulation time and length of postoperative hospital stay were recorded. The clinical efficacy was evaluated by visual analogue scale(VAS) of low back and lower limb, the Japanese Orthopedic Association(JOA) score before and after operation. RESULTS: All patients were follow-up from 26 to 39 months. The subjective symptoms, clinical signs, daily activities and JOA total scores after operation in two groups were significantly higher than those before preoperation(P<0.05);the clinical signs score and total JOA score in the negative group at 3 months after operation were higher than those in the positive group(P<0.05). The VAS score of leg pain in the negative group after 1 and 3 months was less than that in the positive group(P<0.05). Patients 's illness time, postoperative recovery time, hospitalization time and implantation time in the negative group were shorter than those in the positive group(P<0.05). At other time points, there was no significant difference in low pain VAS, leg pain VAS, JOA scores in the two groups(P>0.05). There was no significant difference in the operation time and intraoperative bleeding volume between the two groups(P>0.05). CONCLUSION: Patients with normal electromyography had shorter disease duration than ones with abnormal electromyography in lumbar degenerative disease;after PLIF, patients with normal electromyography recovered faster than ones with abnormal electromyography, but the results of electromyography had no effect on the final prognosis of PLIF surgery.

Engineered lytic phage of Bacillus cereus and its application in milk.

Phages have been approved for use in the food industry to control bacterial contamination in some countries. However, their broader adoption is hindered by some limitations. For instance, the persistence of infectious phages in the food industry can lead to the emergence of resistant bacteria, which negatively impacts the long-term effectiveness of phages. Additionally, the narrow host range of phages limits their effectiveness against various strains. To address these deficiencies, phage engineering has been proposed as a rational approach for modifying phages. In this study, we developed a simple and efficient engineering method for Bacillus cereus phage, using DK1 as an example, to reduce the number of residual phages and expand its range of hosts. Specifically, we knocked out the appendage gene, which codes for the receptor-binding protein, to produce phage progeny with structural defects in their appendages, resulting in the loss of infectivity after host elimination. Furthermore, we used plasmid-mediated means to express different appendage proteins during phage preparation, which allowed altering the host spectrum of the engineered phages without gene insertion. In practical applications, our engineered phages effectively reduced the number of B. cereus in milk and prevented the amplification of active progeny. Our strategy transformed phages from active viruses into more controllable antibacterial agents, making them safer and more efficient for the prevention and control of B. cereus. Moreover, we believe this strategy will help drive the use of engineered phages in the food industry.

Dual-mode immunochromatographic assay based on dendritic gold nanoparticles with superior fluorescence quenching for ultrasensitive detection of E. coli O157:H7.

We presented a colorimetric/fluorescent dual-mode immunochromatographic assay (ICA) for the sensitive detection of Escherichia coli O157:H7. The use of polydopamine (PDA)-modified gold nanoparticles (AuNPs) with broadband absorption allowed for excellent colorimetry signals for the ICA detection. Moreover, the absorption spectrum of PDA-AuNPs significantly overlaps with the excitation and emission spectra of ZnCdSe/ZnS quantum dots (QDs), resulting in effective quenching of the QDs fluorescence due to the inner filter effect. The fluorescence intensity changes induced by PDA-AuNPs were utilized for the sensitive detection of E. coli O157:H7, achieving a detection limit of 9.06 × 101 CFU/mL, which was 46-fold lower than that of traditional AuNPs-based immunoassay. The proposed immunosensor exhibited the recovery rate between 80.12% and 114.69% in detecting actual samples, indicating its reliability and satisfactory accuracy. This study provides insights into dual-mode signal outputs and the ICA development for food safety applications.

Recent advances in phage defense systems and potential overcoming strategies.

Bacteriophages are effective in the prevention and control of bacteria, and many phage products have been permitted and applied in the field. Because bacteriophages are expected to replace other antimicrobial agents like antibiotics, the antibacterial effect of bacteriophage has attracted widespread attention. Recently, the diversified defense systems discovered in the target host have become potential threats to the continued effective application of phages. Therefore, a systematic summary and in-depth illustration of the interaction between phages and bacteria is conducive to the development of this biological control approach. In this review, we introduce different defense systems in bacteria against phages and emphasize newly discovered defense mechanisms in recent years. Additionally, we draw attention to the striking resemblance between defense system genes and antibiotic resistance genes, which raises concerns about the potential transfer of phage defense systems within bacterial populations and its future impact on phage efficacy. Thus, attention should be given to the effects of phage defense genes in practical applications. This article is not exhaustive, but strategies to overcome phage defense systems are also discussed to further promote more efficient use of phages.

Selenium-enriched foods and their ingredients: As intervention for the vicious cycle between autophagy and overloaded stress responses in Alzheimer's disease.

Dysfunctional autophagy induced by excessive reactive oxygen species (ROS) load and inflammation accelerates the development of Alzheimer's disease (AD). Recently, there has been an increasing interest in selenium-enriched ingredients (SEIs), such as selenoproteins, selenoamino acids and selenosugars, which could improve AD through antioxidant and anti-inflammation, as well as autophagy modulating effects. This review indicates that SEIs eliminate excessive ROS by activating the nuclear translocation of nuclear factor erythroid2-related factor 2 (Nrf2) and alleviate inflammation by inhibiting the mitogen-activated protein kinases (MAPKs)/nuclear factor kappa-B (NF-κB) pathway. Furthermore, they can activate the adenosine 5'-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, and subsequently promote amyloid beta (Aß) clearance and reduce memory impairments. SEIs are ubiquitous in many plants and microorganisms, such as Brassicaceae vegetables, yeast, and mushroom. Enzymatic hydrolysis, as well as physical processing, such as thermal, high pressure and microwave treatment, are the main techniques to modify the properties of dietary selenium. This work highlights the fact that SEIs can inhibit inflammation and oxidative stress and provides evidence that supports the potential use of these dietary materials to be a novel strategy for improving AD.

Whole-plant foods and their macromolecules: untapped approaches to modulate neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Recently, sustained neuroinflammatory response in microglia and astrocytes has been found to cause the deposition of amyloid beta plaques and the hyperphosphorylation of tau protein, thereby accelerating AD progression. The lipoxin A4-transcription factor nuclear factor-kappa B and mitogen-activated protein kinase pathways have been shown to play important roles in the regulation of inflammatory processes. There is growing research-based evidence suggesting that dietary whole-plant foods, such as mushrooms and berries, may be used as inhibitors for anti-neuroinflammation. The beneficial effects of whole-plant foods were mainly attributed to their high contents of functional macromolecules including polysaccharides, polyphenols, and bioactive peptides. This review provides up-to-date information on important molecular signaling pathways of neuroinflammation and discusses the anti-neuroinflammatory effects of whole-plant foods. Further, a critical evaluation of plants' macromolecular components that have the potential to prevent and/or relieve AD is provided. This work will contribute to better understanding the pathogenetic mechanism of neuroinflammation in AD and provide new approaches for AD therapy.

Selenium-containing polysaccharide from Spirulina platensis alleviates Cd-induced toxicity in mice by inhibiting liver inflammation mediated by gut microbiota.

Selenium-containing polysaccharide from Spirulina platensis (Se-SPP) has been demonstrated to help in inhibiting cadmium-induced injury in mice, but the underlying mechanism has not been determined. This study aimed to investigate the beneficial effects of Se-SPP on alleviating Cd-induced toxicity in mice by targeting liver inflammatory and gut microbiota. Se-SPP supplementation for 28 days in Cd-induced toxic mice significantly mitigated liver pathological damage and inflammation, which was correlated to the upregulation of antioxidant enzyme activity. Furthermore, Se-SPP effectively restored Cd-induced disruption of the intestinal barrier compared to model group, as indicated by the depletion of Muribaculaceae and the enrichment of Ruminococcaceae. Spearman's correlation analysis revealed that the Se-SPP-altered microbes were highly correlated with inflammation-related indexes in Cd-induced toxic mice. Noteworthily, the modulation of Se-SPP on the Ruminococcaceae population contributed to the improvement of Cd-induced inflammation-related diseases by downregulating the tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the liver. These findings suggested that Se-SPP may act as prebiotics for ameliorating Cd-induced toxicity in mice by inhibiting liver inflammation mediated by gut microbiota, and target-specific microbiota of Cd-induced inflammation-related diseases deserve further attention.

Antioxidant and anti-inflammation effects of dietary phytochemicals: The Nrf2/NF-κB signalling pathway and upstream factors of Nrf2.

Oxidative stress (OS) is created by an imbalance between reactive oxygen species and antioxidant levels. OS promotes inflammation and is associated with many diseases, such as neurodegenerative disorders, diabetes, and cardiovascular disease. Nrf2 and NF-κB are critical in the cellular defence against OS and the regulators of inflammatory responses, respectively. Recent studies revealed that the Nrf2 signalling pathway interacts with the NF-κB signalling pathway in OS. More importantly, many natural compounds have long been recognized to ameliorate OS and inflammation via the Nrf2 and/or NF-κB signalling pathway. Thus, we briefly overview the potential crosstalk between Nrf2 and NF-κB and the upstream regulators of Nrf2 and review the literature on the antioxidant and anti-inflammatory effects of dietary phytochemicals (DPs) that can activate these defence systems. The aim is to provide evidence for the development of DPs into functional food for the regulation of the Nrf2/NF-κB signalling pathway by upstream regulators of Nrf2.

How Nanoparticles Open the Paracellular Route of Biological Barriers: Mechanisms, Applications, and Prospects.

Biological barriers are essential physiological protective systems and obstacles to drug delivery. Nanoparticles (NPs) can access the paracellular route of biological barriers, either causing adverse health impacts on humans or producing therapeutic opportunities. This Review introduces the structural and functional influences of NPs on the key components that govern the paracellular route, mainly tight junctions, adherens junctions, and cytoskeletons. Furthermore, we evaluate their interaction mechanisms and address the influencing factors that determine the ability of NPs to open the paracellular route, which provides a better knowledge of how NPs can open the paracellular route in a safer and more controllable way. Finally, we summarize limitations in the research models and methodologies of the existing research in the field and provide future research direction. This Review demonstrates the in-depth causes for the reversible opening or destruction of the integrity of barriers generated by NPs; more importantly, it contributes insights into the design of NP-based medications to boost paracellular drug delivery efficiency.

Physicochemical Characterization and Antioxidant and Hypolipidaemic Activities of a Polysaccharide From the Fruit of Kadsura coccinea (Lem.) A. C. Smith.

Kadsura coccinea fruit, a novel fruit resource, has attracted wide interest, but the physicochemical characteristics and biological activities of its polysaccharides remain unclear. This study investigated the physicochemical properties of a polysaccharide extracted from K. coccinea fruit polysaccharide (KCFP) and evaluated its antioxidant and hypolipidaemic activities in vitro and in vivo. KCFP is an amorphous, thermally stable pectin heteropolysaccharide with an average molecular weight of 204.6 kDa that is mainly composed of mannose, rhamnose, glucose, galactose, xylose, arabinose, galacturonic acid (molar percentage >70%) and glucuronic acid. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging assays and an iron reducing antioxidant power assay showed that KCFP has strong antioxidant capacity, while the bile acid binding assay showed that KCFP has hypolipidaemic potential in vitro. The antioxidant and hypolipidaemic activities of KCFP were further evaluated in high-fat diet-induced hyperlipidaemic mice. KCFP significantly increased the activities of superoxide dismutase, glutathione peroxidase and catalase, decreased the malondialdehyde content, significantly reduced the total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels, and increased the amount of high-density lipoprotein cholesterol (HDL-C). These findings suggest that KCFP could be used as a functional food to remedy oxidative damage and hyperlipidaemia.

Polysaccharides from Cordyceps militaris prevent obesity in association with modulating gut microbiota and metabolites in high-fat diet-fed mice.

Improved gut microbes and nutritious metabolites have been considered as the mediators of health benefits from indigestible polysaccharides, but their role in the anti-obesity effect of polysaccharides from Cordyceps militaris (CMP) remains elusive. This study aims to explore the potential mediators of the anti-obesity effects of CMP in high-fat diet (HFD)-fed mice using 16S rRNA sequencing and untargeted metabolomics analysis. The results showed that CMP supplementation in HFD-fed mice reduced body weight, fat accumulation, pro-inflammatory cytokine levels, and impaired glucose tolerance as well as gut barrier. Moreover, the CMP reversed the HFD-induced gut microbiota dysbiosis, as indicated by the elevated population of Alloprevotella, Parabacteroides, Butyricimonas, and Alistipes; and decreased population of Negativebacillus, in addition to altered levels of metabolites, such as brassicasterol and 4'-O-methylkanzonol W. Notably, CMP prevented obesity in association with the altered gut microbes and metabolites. These findings suggest that CMP may serve as a potential prebiotic agent to modulate specific gut microbes and related metabolites, which play a critical role in its preventing obesity-related diseases.

A Flagella Hook Coding Gene flgE Positively Affects Biofilm Formation and Cereulide Production in Emetic Bacillus cereus.

Bacillus cereus, an important foodborne pathogen, poses a risk to food safety and quality. Robust biofilm formation ability is one of the key properties that is responsible for the food contamination and food poisoning caused by B. cereus, especially the emetic strains. To investigate the mechanism of biofilm formation in emetic B. cereus strains, we screened for the mutants that fail to form biofilms by using random mutagenesis toward B. cereus 892-1, an emetic strain with strong biofilm formation ability. When knocking out flgE, a flagellar hook encoding gene, the mutant showed disappearance of flagellar structure and swimming ability. Further analysis revealed that both pellicle and ring presented defects in the null mutant compared with the wild-type and complementary strains. Compared with the flagellar paralytic strains Δ motA and Δ motB, the inhibition of biofilm formation by Δ flgE is not only caused by the inhibition of motility. Interestingly, Δ flgE also decreased the synthesis of cereulide. To our knowledge, this is the first report showing that a flagellar component can both affect the biofilm formation and cereulide production in emetic B. cereus, which can be used as the target to control the biohazard of emetic B. cereus.

Polysaccharide from Agrocybe cylindracea prevents diet-induced obesity through inhibiting inflammation mediated by gut microbiota and associated metabolites.

Polysaccharide from Agrocybe cylindracea (ACP) has been demonstrated with various health benefits, but its anti-obesity effect and underlying mechanisms remain poorly understood. This study aimed to investigate the beneficial effects of ACP in high-fat diet (HFD)-induced obese mice by targeting gut microbiota and metabolites. 9-week ACP supplementation in HFD-fed mice reduced body weight, adipose accumulation, impaired insulin resistance, lipid levels, and liver injuries, which were negatively correlated to the pro-inflammatory factors, particularly tumor necrosis factor-alpha (TNF-α) and interleukin- 6 (IL-6). Moreover, ACP not only restored HFD-induced gut disorder, as indicated by the depletion of Desulfovibrio and Oscillibacter and the enrichment of the Bacteroides, Parabacteroides, Butyricimonas, and Dubosiella, but also positively regulated gut metabolites such as solavetivone and N-acetylneuraminic acid. Spearman's correlation analysis revealed that the ACP-altered microbes and metabolites were highly correlated with inflammation-related indexes. Notably, ACP greatly lowered the obesity-related TNF-α- and IL-6-levels partially by reducing Desulfovibrio and increasing Parabacteroides abundances, together with the associated decrease of solavetivone level. These findings suggest that ACP may be used as a prebiotic agent to prevent diet-induced obesity, and target-specific microbiota and metabolites may have unique therapeutic promise for inflammation-related diseases.

Novel Selenium Peptides Obtained from Selenium-Enriched Cordyceps militaris Alleviate Neuroinflammation and Gut Microbiota Dysbacteriosis in LPS-Injured Mice.

Increasing attention focuses on the relationship between neuroinflammation and Alzheimer's disease (AD). The reports on the microbiota-gut-brain axis reveal that the regulation by gut microbiota is an effective way to intervene in neuroinflammation-related AD. In this study, two novel selenium peptides (Se-Ps), VPRKL(Se)M (Se-P1) and RYNA(Se)MNDYT (Se-P2), with neuroprotection effects were obtained from Se-enriched Cordyceps militaris. Se-P1 and Se-P2 pre-protection led to a 30 and 33% increase in the PC-12 cell viability compared to the damage group, respectively. Moreover, Se-Ps exhibited a significant pre-protection against LPS-induced inflammatory and oxidative stress in the colon and brain by inhibiting the production of pro-inflammatory mediators (p < 0.05) and malondialdehyde, as well as promoting anti-inflammatory cytokine level and antioxidant enzyme activity (p < 0.05), which may alleviate the cognitive impairment in LPS-injured mice (p < 0.05). Se-Ps not only repaired the intestinal mucosa damage of LPS-injured mice but also had a positive effect on gut microbiota dysbacteriosis by increasing the abundance of Lactobacillus and Alistipes and decreasing the abundance of Akkermansia and Bacteroides. Collectively, the antioxidant, anti-inflammatory, and regulating properties on gut microflora of Se-Ps contribute to their neuroprotection, supporting that Se-Ps could be a promising dietary supplement in the prevention and/or treatment of AD.

Controlled PAH-mediated method with enhanced optical properties for simple, stable immunochromatographic assays.

Despite their potential for signal amplification in immunochromatographic assays (ICAs) with Au nanoparticles (AuNPs) as probes, metal growth methods are of limited practical applicability given their complex non-specificity and lack of robust growth schemes. Here, we propose a novel method of polyallylamine hydrochloride (PAH)-mediated metal growth for the detection of Escherichia coli O157:H7 by AuNP-ICA. The developed method relies on the highly controlled growth of Cu shells on the AuNP core and allows one to achieve highly enhanced colorimetric signals by controlling PAH as the growth framework. The introduction of PAH eliminates the non-specific adsorption of Cu ions on the nitrocellulose membrane and thus provides maximized and effective signal-to-noise ratios to achieve a detection limit of 9.8 CFU/mL for E. coli O157:H7. Moreover, the newly developed detection method exhibits good reproducibility (coefficient of variation <13%), remarkable stability, and practical applicability. The PAH-mediated signal enhancement system paves the way to the realization of stable metal growth methods based on Au, Ag, and other metals and is well suited for the rapid, stable, and sensitive detection of food-borne pathogens using the AuNP-ICA platform.