Skin microbiome profiling reveals the crucial role of microbial metabolites in anti-photoaging.

BACKGROUND: Skin microbiota is essential for health maintenance. Photoaging is the primary environmental factor that affects skin homeostasis, but whether it influences the skin microbiota remains unclear. OBJECTIVE: The objective of this study is to investigate the relationship between photoaging and skin microbiome. METHODS: A cohort of senior bus drivers was considered as a long-term unilateral ultraviolet (UV) irradiated population. 16S rRNA amplicon sequencing was conducted to assess skin microbial composition variations on different sides of their faces. The microbiome characteristics of the photoaged population were further examined by photoaging guinea pig models, and the correlations between microbial metabolites and aging-related cytokines were analyzed by high-throughput sequencing and reverse transcription polymerase chain reaction. RESULTS: Photoaging decreased the relative abundance of microorganisms including Georgenia and Thermobifida in human skin and downregulated the generation of skin microbe-derived antioxidative metabolites such as ectoin. In animal models, Lactobacillus and Streptobacillus abundance in both the epidermis and dermis dropped after UV irradiation, resulting in low levels of skin antioxidative molecules and leading to elevated expressions of the collagen degradation factors matrix metalloproteinase (MMP)-1 and MMP-2 and inflammatory factors such as interleukin (IL)-1ß and IL-6. CONCLUSIONS: Skin microbial characteristics have an impact in photoaging and the loss of microbe-derived antioxidative metabolites impairs skin cells and accelerates the aging process. Therefore, microbiome-based therapeutics may have potential in delaying skin aging.

Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

Dual-recognition colorimetric platform based on porous Au@Pt nanozymes for highly sensitive washing-free detection of Staphylococcus aureus.

A dual-recognition strategy is reported to construct a one-step washing and highly efficient signal-transduction tag system for high-sensitivity colorimetric detection of Staphylococcus aureus (S. aureus). The porous (gold core)@(platinum shell) nanozymes (Au@PtNEs) as the signal labels show highly efficient peroxidase mimetic activity and are robust. For the sake of simplicity the detection involved the use of a vancomycin-immobilized magnetic bead (MB) and aptamer-functionalized Au@PtNEs for dual-recognition detection in the presence of S. aureus. In addition, we designed a magnetic plate to fit the 96-well microplate to ensure consistent magnetic properties of each well, which can quickly remove unreacted Au@PtNEs and sample matrix while avoiding tedious washing steps. Subsequently, Au@PtNEs catalyze hydrogen peroxide (H2O2) to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) generating a color signal. Finally, the developed Au@PtNEs-based dual-recognition washing-free colorimetric assay displayed a response in the range of S. aureus of 5 × 101-5 × 105 CFU/mL, and the detection limit was 40 CFU/mL within 1.5 h. In addition, S. aureus-fortified samples were analyzed to further evaluate the performance of the proposed method, which yielded average recoveries ranging from 93.66 to 112.44% and coefficients of variation (CVs) within the range 2.72-9.01%. These results furnish a novel horizon for the exploitation of a different mode of recognition and inexpensive enzyme-free assay platforms as an alternative to traditional enzyme-based immunoassays for the detection of other Gram-positive pathogenic bacteria.

Isolation and characterization of a novel Bacillus cereus bacteriophage vBce-DP7.

Foodborne pathogens have become a major concern for public health. Bacillus cereus, a representative foodborne pathogen, is particularly challenging due to its ability to cause food poisoning and its resilient spores that are difficult to completely eradicate. Therefore, it is crucial to develop measures to prevent and control B. cereus. Bacteriophages, which are high specific towards their host strains and cannot infect eukaryotes, have proven to be effective in combating foodborne pathogens and are safe for human use. In this study, we isolated and characterized a novel bacteriophage named vBce-DP7 that specifically targets B. cereus strains belonging to three different sequence types (STs). Phage vBce-DP7 is a lytic one and has a short latent time of only 15 minutes. Moreover, it exhibited a good temperature tolerance, retaining high activity across a broad range of 4 - 55 °C. Additionally, its activity remains unaffected within a wide pH range spanning from 2 - 10. Interestingly, with only 4% genetic similarity with known bacteriophages, vBce-BP7 shows a possible classification on a family level though it shares many similar functional proteins with Salasmaviridae bacteriophages. Taken together, vBce-BP7 demonstrates its significant potential for further exploration in terms of phage diversity and its application in controlling B. cereus.

Progress of Infection and Replication Systems of Hepatitis B Virus.

Despite the long-standing availability of effective prophylaxis, chronic hepatitis B virus (HBV) infection remains a formidable public health threat. Antiviral treatments can limit viral propagation, but prolonged therapy is necessary to control HBV replication. Robust in vitro models of HBV infection are indispensable prerequisites for elucidating viral pathogenesis, delineating virus-host interplay and developing novel therapeutic, preventative countermeasures. Buoyed by advances in molecular techniques and tissue culture systems, investigators have engineered numerous in vitro models of the HBV life cycle. However, all current platforms harbor limitations in the recapitulation of natural infection. In this article, we comprehensively review the HBV life cycle, provide an overview of existing in vitro HBV infection and replication systems, and succinctly present the benefits and caveats in each model with the primary objective of constructing refined experimental models that closely mimic native viral infection and offering robust support for the ambitious "elimination of hepatitis by 2030" initiative.

Characterization of the novel phage vB_BceP_LY3 and its potential role in controlling Bacillus cereus in milk and rice.

Bacillus cereus is a foodborne pathogen that induces vomiting and diarrhea in affected individuals. It exhibits resistance to traditional sterilization methods and has a high contamination rate in dairy products and rice. Therefore, the development of a new food safety controlling strategy is necessary. In this research, we isolated and identified a novel phage named vB_BceP_LY3, which belongs to a new genus of the subfamily Northropvirinae. This phage demonstrates a short latency period and remains stable over a wide range of temperatures (4-60 °C) and pH levels (4-11). The 28,124 bp genome of LY3 does not contain any antibiotic-resistance genes or virulence factors. With regards to its antibacterial properties, LY3 not only effectively inhibits the growth of B. cereus in TSB (tryptic soy broth), but also demonstrates significant inhibitory effects in various food matrices. Specifically, LY3 treatment at 4 °C with a high MOI (MOI = 10,000) can maintain B. cereus levels below the detection limit for up to 24 h in milk. LY3 represents a safe and promising biocontrol agent against B. cereus, possessing long-term antibacterial capabilities and stability.

Washed microbiota transplantation promotes homing of group 3 innate lymphoid cells to the liver via the CXCL16/CXCR6 axis: a potential treatment for metabolic-associated fatty liver disease.

Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.

Precisely Designed Ultra-Small CoP Nanoparticles-decorated Hollow Carbon Nanospheres as Highly Efficient Host in Lithium-Sulfur Batteries.

Designing porous carbon materials with metal phosphides as host materials holds promise for enhancing the cyclability and durability of lithium-sulfur (Li-S) batteries by mitigating sulfur poisoning and exhibiting high electrocatalytic activity. Nevertheless, it is urgent to precisely control the size of metal phosphides to further optimize the polysulfide conversion reaction kinetics of Li-S batteries. Herein, a subtlety regulation strategy was proposed to obtain ultra-small CoP nanoparticles-decorated hollow carbon nanospheres (CoP@C) by using spherical polyelectrolyte brush (SPB) as the template with stabilizing assistance from polydopamine coating, which also works as carbon source. Leveraging the electrostatic interaction between SPB and Co2+, ultra-small Co particles with sizes measuring 5.5 ± 2.6 nm were endowed after calcination. Subsequently, through a gas-solid phosphating process, these Co particles were converted into CoP nanoparticles with significantly finer sizes (7.1 ± 3.1 nm) compared to state-of-the-art approaches. By uniformly distributing the electrocatalyst nanoparticles on hollow carbon nanospheres, CoP@C facilitated the acceleration of Li ion diffusion and enhanced the conversion reaction kinetics of polysulfides through adsorption-diffusion synergy. As a result, Li-S batteries utilizing the CoP@C/S cathode demonstrated an initial specific discharge capacity of 850.0 mAh g-1 at 1.0 C, with a low-capacity decay rate of 0.03% per cycle.

Electric-field-controlled electronic structures and quantum transport in monolayer InSe nanoribbons.

Electronic structures and quantum transport properties of the monolayer InSe nanoribbons are studied by adopting the tight-binding model in combination with the lattice Green function method. Besides the normal bulk and edge electronic states, a unique electronic state dubbed as edge-surface is found in the InSe nanoribbon with zigzag edge type. In contrast to the zigzag InSe nanoribbon, a singular electronic state termed as bulk-surface is observed along with the normal bulk and edge electronic states in the armchair InSe nanoribbons. Moreover, the band gap, the transversal electron probability distributions in the two sublayers, and the electronic state of the topmost valence subband can be manipulated by adding a perpendicular electric field to the InSe nanoribbon. Further study shows that the charge conductance of the two-terminal monolayer InSe nanoribbons can be switched on or off by varying the electric field strength. In addition, the transport of the bulk electronic state is delicate to even a weak disorder strength, however, that of the edge and edge-surface electronic states shows a strong robustness against to the disorders. These findings may be helpful to understand the electronic characteristics of the InSe nanostructures and broaden their potential applications in two-dimensional nanoelectronic devices as well.

A general strategy for all-solid-state batteries with agglomeration-free and high conductivity achieved by improving the interface compatibility of fillers and polymer matrix.

Composite solid electrolytes (CSEs) composed of polymer matrix and inorganic fillers show considerable potential for applications in all-solid-state lithium (Li) metal batteries. However, challenges such as fillers agglomeration and low lithium ion transference number (tLi+) remain significant obstacles to the practical application of CSEs. Herein, a general strategy of graft polymerization on the fillers surface to modulate the interface compatibility with the polymer matrix is proposed, and CSEs are prepared to verify the feasibility. The microstructure and composition of the surface coating of the fillers are analyzed, with subsequent studies of the fillers distribution within the CSEs confirming the improved interface compatibility. The enhancement of interface compatibility facilitates uniform dispersion of fillers, thereby greatly improving the utilization of fillers. CSEs exhibits high ionic conductivity (0.163 mS·cm-1 at 30 °C) and tLi+ (0.77), which gives the battery excellent rate performance and cycle stability. Therefore, chemical grafting of polymer onto the fillers surface to enhance the interface compatibility with the polymer matrix represents a promising strategy for the practical application of solid-state batteries.

Relay-Type Catalysis by a Dual-Metal Single-Atom System in a Waste Biomass Derivative Host for High-Rate and Durable Li-S Batteries.

An environmental-friendly and sustainable carbon-based host is one of the most competitive strategies for achieving high loading and practicality of Li-S batteries. However, the polysulfide conversion reaction kinetics is still limited by the nonuniform or monofunctional catalyst configuration in the carbon host. In this work, we propose a catalysis mode based on "relay-type" co-operation by adjacent dual-metal single atoms for high-rate and durable Li-S batteries. A discarded sericin fabric-derived porous N-doped carbon with a stacked schistose structure is prepared as the high-loading sulfur (84 wt %) host by a facile ionothermal method, which further enables the uniform anchoring of Fe/Co dual-metal single atoms. This multifunctional host enables superior lithiophilic-sulfiphilic and electrocatalytic capabilities contributed by the "relay-type" single-atom modulation effects on different conversion stages of liquid polysulfides and solid Li2S2/Li2S, leading to the suppression of the "shuttle effect", alleviation of nucleation and decomposition barriers of Li2Sx, and acceleration of polysulfide conversion kinetics. The corresponding Li-S batteries exhibit a high specific capacity of 1399.0 mA h g-1, high-rate performance up to 10 C, and excellent cycling stability over 1000 cycles. They can also endure the high sulfur loading of 8.5 mg cm-2 and the lean electrolyte condition and yield an areal capacity as high as 8.6 mA h cm-2. This work evidentially demonstrates the potential of waste biomass reutilization coupled with the design of a single-atom system for practical Li-S batteries with high energy density.

An In Vitro Evaluation of the Effect of Bifidobacterium longum L556 on Microbiota Composition and Metabolic Properties in Patients with Coronary Heart Disease (CHD).

Bifidobacterium longum (B. longum) is a beneficial anaerobic bacteria that may improve cardiovascular disease (CVD). We studied B. longum L556, isolated from healthy human feces, in coronary heart disease (CHD) patients through anaerobic fermentation in vitro. Results showed that B. longum L556 increased Lactobacillus, Faecalibacterium, Prevotella, and Alistipes, while reducing Firmicutes to Bacteroidetes, Eggerthella, Veillonella, Holdemanella, and Erysipelotrichaceae_UCG-003 in the gut microbiota of CHD patients. B. longum L556 also enhanced anti-inflammatory effects by modulating gut microbiota and metabolites like SCFAs. Additionally, it regulated lipid and amino acid metabolism in fermentation metabolites from the CHD group. These findings suggest that B. longum L556 has potential for improving CHD by modulating the intestinal microbiota, promoting SCFA production, and regulating lipid metabolism and inflammation.

Exome-Based Amino Acid Optimization: A Dietary Strategy to Satisfy Human Nutritional Demands and Enhance Muscle Strength in Breast Tumor Mice Undergoing Chemotherapy.

Breast cancer patients undergoing chemotherapy often experience muscle wasting and weakness, which impact their quality of life. A potential solution lies in customizing amino acid compositions based on exome-derived formulations (ExAAs). The study hypothesized that tailoring dietary amino acids using ExAAs could enhance muscle health. Theoretical amino acid requirements were calculated from the genome's exome region, and a breast cancer mouse model undergoing paclitaxel treatment was established. The mice were supplemented with a cancer-specific nutritional formula (QJS), and the effects of QJS and amino acid-adjusted QJS (adjQJS) were compared. Both formulations improved the nutritional status without compromising tumor growth. Notably, adjQJS significantly enhanced muscle strength compared to QJS (1.51 ± 0.25 vs. 1.30 ± 0.08 fold change, p < 0.05). Transcriptome analysis revealed alterations in complement and coagulation cascades, with an observed upregulation of C3 gene expression in adjQJS. Immune regulation also changed, showing a decrease in B cells and an increase in monocytes in skeletal muscle with adjQJS. Importantly, adjQJS resulted in a notable increase in Alistipes abundance compared to QJS (10.19 ± 0.04% vs. 5.03 ± 1.75%). This study highlights the potential of ExAAs as valuable guide for optimizing amino acid composition in diets for breast cancer patients undergoing chemotherapy.

Cold-tolerance mechanisms in foodborne pathogens: Escherichia coli and Listeria monocytogenes as examples.

The cold chain is an integral part of the modern food industry. Low temperatures can effectively alleviate food loss and the transmission of foodborne diseases caused by microbial reproduction. However, recent reports have highlighted shortcomings in the current cold chain technology's ability to prevent and control cold-tolerant foodborne pathogens. Furthermore, it has been observed that certain cold-chain foods have emerged as new sources of infection for foodborne disease outbreaks. Consequently, there is a pressing need to enhance control measures targeting cold-tolerant pathogens within the existing cold chain system. This paper aims to review the recent advancements in understanding the cold tolerance mechanisms of key model organisms, identify key issues in current research, and explore the potential of utilizing big data and omics technology in future studies.

Rapid and sensitive lateral flow biosensor for the detection of GII human norovirus based on immunofluorescent nanomagnetic microspheres.

Human norovirus (HuNoV) is the most predominant viral agents of acute gastroenteritis. Point-of-care testing (POCT) based on lateral flow immunochromatography (LIFC) has become an important tool for rapid diagnosis of HuNoVs. However, low sensitivity and lack of quantitation are the bottlenecks of traditional LIFC. Thus, we established a rapid and accurate technique that combined immunomagnetic enrichment (IM) with LFIC to identify GII HuNoVs in fecal specimens. Before preparing immunofluorescent nanomagnetic microspheres and achieving the effect of HuNoV enrichment in IM and fluorescent signal in LFIC, amino-functionalized magnetic beads (MBs) and carboxylated quantum dots (QDs) were coupled at a mass ratio of 4:10. Anti-HuNoV monoclonal antibody was then conjugated with QDs-MB. The limit of detection was 1.56 × 104 copies/mL, and the quantitative detection range was 1.56 × 104 copies/mL-1 × 106 copies/mL under optimal circumstances. The common HuNoV genotypes GII.2, GII.3, GII.4, and GII.17 can be detected, there was no cross-reaction with various enteric viruses, including rotavirus, astrovirus, enterovirus, and sapovirus. A comparison between IM-LFIC and RT-qPCR for the detection of 87 fecal specimens showed a high level of agreement (kappa = 0.799). This suggested that the method is rapid and sensitive, making it a promising option for point-of-care testing in the future.

In Vitro Lactic Acid Bacteria Anti-Hepatitis B Virus (HBV) Effect and Modulation of the Intestinal Microbiota in Fecal Cultures from HBV-Associated Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC), being ranked as the top fifth most prevalent cancer globally, poses a significant health challenge, with a considerable mortality rate. Hepatitis B virus (HBV) infection stands as the primary factor contributing to HCC, presenting substantial challenges in its treatment. This study aimed to identify lactic acid bacteria (LAB) with anti-HBV properties and evaluate their impact on the intestinal flora in HBV-associated HCC. Initially, two LAB strains, Levilactobacillus brevis SR52-2 (L. brevis SR52-2) and LeviLactobacillus delbrueckii subsp. bulgaicus Q80 (L. delbrueckii Q80), exhibiting anti-HBV effects, were screened in vitro from a pool of 498 LAB strains through cell experiments, with extracellular expression levels of 0.58 ± 0.05 and 0.65 ± 0.03, respectively. These strains exhibited the capability of inhibiting the expression of HBeAg and HBsAg. Subsequent in vitro fermentation, conducted under simulated anaerobic conditions mimicking the colon environment, revealed a decrease in pH levels in both the health control (HC) and HCC groups influenced by LAB, with a more pronounced effect observed in the HC group. Additionally, the density of total short-chain fatty acids (SCFAs) significantly increased (p < 0.05) in the HCC group. Analysis of 16S rRNA highlighted differences in the gut microbiota (GM) community structure in cultures treated with L. brevis SR52-2 and L. delbrueckii Q80. Fecal microflora in normal samples exhibited greater diversity compared to HBV-HCC samples. The HCC group treated with LAB showed a significant increase in the abundance of the phyla Firmicutes, Bacteroidetes and Actinobacteria, while Proteobacteria significantly decreased compared to the untreated HCC group after 48 h. In conclusion, the findings indicate that LAB, specifically L. brevis SR52-2 and L. delbrueckii Q80, possessing antiviral properties, contribute to an improvement in gastrointestinal health.

An ultrasensitive smartphone-assisted bicolor-ratiometric fluorescence sensing platform based on a "noise purifier" for point-of-care testing of pathogenic bacteria in food.

Non-specific binding in fluorescence resonance energy transfer (FRET) remains a challenge in foodborne pathogen detection, resulting in interference of high background signals. Herein, we innovatively reported a dual-mode FRET sensor based on a "noise purifier" for the ultrasensitive quantification of Escherichia coli O157:H7 in food. An efficient FRET system was constructed with polymyxin B-modified nitrogen-sulfur co-doped graphene quantum dots (N, S-GQDs@PMB) as donors and aptamer-modified yellow carbon dots (Y-CDs@Apt) as acceptors. Magnetic multi-walled carbon nanotubes (Fe@MWCNTs) were employed as a "noise purifier" to reduce the interference of the fluorescence background. Under the background purification mode, the sensitivity of the dual-mode signals of the FRET sensor has increased by an order of magnitude. Additionally, smartphone-assisted colorimetric analysis enabled point-of-care detection of E. coli O157:H7 in real samples. The developed sensing platform based on a "noise purifier" provides a promising method for ultrasensitive on-site testing of trace pathogenic bacteria in various foodstuffs.

A systematic review and meta-analysis indicates a high risk of human noroviruses contamination in vegetable worldwide, with GI being the predominant genogroup.

Human noroviruses (HuNoVs) are the most predominant viral agents of acute gastroenteritis. Vegetables are important vehicles of HuNoVs transmission. This study aimed to assess the HuNoVs prevalence in vegetables. We searched the Web of Science, Excerpta Medica Database, PubMed, and Cochrane databases until June 1, 2023. A total of 27 studies were included for the meta-analysis. Statistical analysis was conducted using Stata 14.0 software. This analysis showed that the pooled HuNoVs prevalence in vegetables was 7 % (95 % confidence interval (CI): 3-13) worldwide. The continent with largest number of studies was Europe, and the highest number of samples was lettuce. As revealed by the results of the subgroup meta-analysis, the prevalence of GI genogroup was the highest (3 %, 95 % CI: 1-7). A higher prevalence was seen in vegetables from farms (18 %, 95 % CI: 5-37), while only 4 % (95 % CI: 1-8) in retail. The HuNoVs prevalence of ready-to-eat vegetables and non-ready-to-eat vegetables was 2 % (95 % CI: 0-8) and 9 % (95 % CI: 3-16), respectively. The prevalence by quantitative real time RT-PCR was 8 % (95 % CI: 3-15) compared to 3 % (95 % CI: 0-13) by conventional RT-PCR. Furthermore, the HuNoVs prevalence in vegetables was 6 % (95 % CI: 1-14) in ISO pretreatment method and 8 % (95 % CI: 1-19) in non-ISO method, respectively. This study is helpful in comprehensively understanding the prevalence of HuNoVs contamination in vegetables worldwide.

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.

Therapeutic applications of gut microbes in cardiometabolic diseases: current state and perspectives.

Cardiometabolic disease (CMD) encompasses a range of diseases such as hypertension, atherosclerosis, heart failure, obesity, and type 2 diabetes. Recent findings about CMD's interaction with gut microbiota have broadened our understanding of how diet and nutrition drive microbes to influence CMD. However, the translation of basic research into the clinic has not been smooth, and dietary nutrition and probiotic supplementation have yet to show significant evidence of the therapeutic benefits of CMD. In addition, the published reviews do not suggest the core microbiota or metabolite classes that influence CMD, and systematically elucidate the causal relationship between host disease phenotypes-microbiome. The aim of this review is to highlight the complex interaction of the gut microbiota and their metabolites with CMD progression and to further centralize and conceptualize the mechanisms of action between microbial and host disease phenotypes. We also discuss the potential of targeting modulations of gut microbes and metabolites as new targets for prevention and treatment of CMD, including the use of emerging technologies such as fecal microbiota transplantation and nanomedicine. KEY POINTS: • To highlight the complex interaction of the gut microbiota and their metabolites with CMD progression and to further centralize and conceptualize the mechanisms of action between microbial and host disease phenotypes. • We also discuss the potential of targeting modulations of gut microbes and metabolites as new targets for prevention and treatment of CMD, including the use of emerging technologies such as FMT and nanomedicine. • Our study provides insight into identification-specific microbiomes and metabolites involved in CMD, and microbial-host changes and physiological factors as disease phenotypes develop, which will help to map the microbiome individually and capture pathogenic mechanisms as a whole.