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RNA editing is a crucial post-transcriptional process that influences gene expression and increases the diversity of the proteome as a result of amino acid substitution. Recently, the APOBEC3 family has emerged as a significant player in this mechanism, with APOBEC3A (A3A) having prominent roles in base editing during immune and stress responses. APOBEC3B (A3B), another family member, has gained attention for its potential role in generating genomic DNA mutations in breast cancer. In this study, we coupled an inducible expression cell model with a novel methodology for identifying differential variants in RNA (DVRs) to map A3B-mediated RNA editing sites in a breast cancer cell model. Our findings indicate that A3B engages in selective RNA editing including targeting NEAT1 and MALAT1 long non-coding RNAs that are often highly expressed in tumour cells. Notably, the binding of these RNAs sequesters A3B and suppresses global A3B activity against RNA and DNA. Release of A3B from NEAT1/MALAT1 resulted in increased A3B activity at the expense of A3A activity suggesting a regulatory feedback loop between the two family members. This research substantially advances our understanding of A3B's role in RNA editing, its mechanistic underpinnings, and its potential relevance in the pathogenesis of breast cancer., Competing Interests: Competing interests CZ, KM, OR, and PAC are current or past employees of The Institute of Cancer Research, which has a commercial interest in the discovery and development of A3B inhibitors and operates a reward to inventors’ scheme. Separately, CZ, MW, FX, and XL are employees of Shanghai Institute of Biological Products, an entity presently engaged in the commercial development of therapeutic biologics. No conflicts of interest have been reported by the remaining authors. Ethics approval and consent to participate The authors confirm that all methods were performed in accordance with the relevant guidelines and regulations., (© 2024. The Author(s).)

Modulating gut microbiota composition through probiotic administration has been proposed as a novel therapy for type 2 diabetes mellitus (T2DM), and fermented milk is arguably the most common and ideal probiotic carrier. The present meta-analysis was performed to assess the effects of probiotic fermented milk supplementation on glucose and lipid metabolism parameters and inflammatory markers in patients with T2DM using published data from randomized controlled trials (RCTs). The PubMed, Web of Science, and Cochrane Library databases were searched for relevant RCTs. A random-effects model was used to generate the weighted mean difference (WMD) and 95% confidence interval (95% CI). Probiotic fermented milk supplementation reduced the levels of fasting plasma glucose (MD = -17.01, 95% CI -26.43, -7.58 mg/dL; n = 7), hemoglobin A1c (MD = -0.47, 95% CI -0.74, -0.21%; n = 7), total cholesterol (MD = -5.15, 95% CI -9.52, -0.78 mg/dL; n = 7), and C-reactive protein (MD = -0.25, 95% CI -0.43, -0.08; n = 3) but did not significantly affect the levels of HOMA-IR (MD = -0.89, 95% CI -2.55, 0.78; n = 3), triglyceride (MD = -4.69, 95% CI -14.67, 5.30 mg/dL; n = 6), low-density lipoprotein cholesterol (MD = -4.25, 95% CI -8.63, 0.13 mg/dL; n = 7), high-density lipoprotein cholesterol (MD = 1.20, 95% CI -0.96, 3.36 mg/dL; n = 7), and tumor necrosis factor-alpha (MD: -0.58, 95% CI -1.47, 0.32 pg/mL; n = 2). In summary, the present findings provide a crude indication of the potential benefits of probiotic fermented milk supplementation in improving glucose and lipid metabolism and inflammation in patients with T2DM. However, more robust evidence is needed to determine the clinical significance of probiotic fermented milk in the management of T2DM.

The effective monitoring of microalgae cultivation is crucial for optimizing their energy utilization efficiency. In this paper, a quantitative analysis method, using microalgae images based on two convolutional neural networks, EfficientNet (EFF) and residual network (RES), is proposed. Suspension samples prepared from two types of dried microalgae powders, Rhodophyta (RH) and Spirulina (SP), were used to mimic real microalgae cultivation settings. The method's prediction accuracy of the algae concentration ranges from 0.94 to 0.99. RH, with a distinctively pronounced red-green-blue value shift, achieves a higher prediction accuracy than SP. The prediction results of the two algorithms were significantly superior to those of a linear regression. Additionally, RES outperforms EFF in terms of its generalization ability and robustness, which is attributable to its distinct residual block architecture. The RES provides a viable approach for the image-based quantitative analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Lactobacillus plantarum has been shown to improve glucose and lipid metabolism in mouse models of type 2 diabetes mellitus (T2DM). However, it remains unclear whether such benefits extend to humans. A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to clarify the effect of L. plantarum supplementation on glucose and lipid metabolism in T2DM and prediabetes. The PubMed, Cochrane, and Web of Science databases were searched. A random-effects model was used to estimate the pooled mean difference with 95% CI (confidence interval). L. plantarum supplementation reduced the levels of fasting plasma glucose (-0.41, 95%CI -0.63, -0.19 mg/dL; n = 5) and hemoglobin A1c (-0.2, 95%CI: -0.3, 0%; n = 4). A non-statistically significant tendency towards improvements in the Homeostatic Model Assessment for Insulin Resistance (MD: -0.74, 95%CI: -1.72, 0.25; n = 3), low-density lipoprotein cholesterol (-6.87; 95%CI: -15.03, 1.29 mg/dL; n = 3), high-density lipoprotein cholesterol (MD: 1.34; 95%CI: -0.78, 3.46 mg/dL; n = 3), triglyceride (MD: -3.90; 95%CI: -11.05, 3.24 mg/dL; n = 3), and total cholesterol (MD: -4.88; 95%CI: -11.84, 2.07 mg/dL; n = 3) was observed with the supplementation. In summary, while the evidence from the currently available RCTs provides a crude indication that L. plantarum supplementation might improve glucose and lipid metabolism in patients with T2DM and prediabetes, the benefits of the supplementation are likely subtle, and its clinical significance requires further investigation., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Lacticaseibacillus paracasei has been regarded as a probiotic bacterium because of its role in anti-inflammatory properties and maintenance of intestinal barrier permeability. Here, we explored the anticolitic effects and mechanism of L. paracasei CCFM1222. The results showed that L. paracasei CCFM1222 supplementation could suppress the disease activity index (DAI) and colon length shortening in colitis mice, accompanied by a moderate increase in colonic tight junction proteins (ZO-1, occludin and claudin-1). L. paracasei CCFM1222 intervention significantly suppressed the levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and significantly elevated the activities of antioxidant enzymes (including SOD, GSH-Px, and CAT) in the colon by regulating the TLR4/MyD88/NF-κB and Nrf2 signaling pathways in colitis mice. In addition, L. paracasei CCFM1222 significantly shifted the gut microbiota, including elevating the abundance of Catabacter, Ruminiclostridium 9, Alistipes, and Faecalibaculum, as well as reducing the abundance of Mucispirillum, Escherichia-Shigella, and Salmonella, which was associated with the improvement of colonic barrier damage. Overall, these results suggest that L. paracasei CCFM1222 is a good candidate for probiotic of improving colonic barrier damage and associated diseases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Influenza virus is a prominent cause of respiratory illness in humans. Current influenza vaccines offer strain-specific immunity, while provide limited protection against drifted strains. Broad-spectrum influenza vaccines can induce broad and long-term immunity, and thus are regarded as a future direction for the development of next-generation influenza vaccines. In this study, we have conceptualized a novel mRNA-based multi-antigen influenza vaccine consisting of three conserved antigens of influenza A virus, including the ectodomain of the M2 ion channel (M2e), the long alpha helix of haemagglutinin stalk region (LAH), and nucleoprotein (NP). The vaccine design aims to enhance its potency and promote the development of a future broad-spectrum influenza vaccine. Our mRNA-based vaccine demonstrated potent humoral and cellular responses throughout the time points of the murine model, inducing viral neutralizing antibodies, antibody-dependent cell cytotoxicity effect mediating antibodies and cross-reactive CD8 + T cell immune responses. The vaccine conferred broad protection against H1N1, H3N2, and H9N2 viruses. Moreover, the single-cell transcriptional profiling of T cells in the spleens of vaccinated mice revealed that the mRNA-based vaccine significantly promoted CD8 + T cells and memory T cells by prime-boost immunization. Our results suggest that the mRNA-based influenza vaccine encoding conserved proteins is a promising approach for eliciting broadly protective humoral and cellular immunity against various influenza viruses.

Background: Bifidobacterium pseudolongum is widely exists in mammal gut and its abundance is associated with human and animal health. The present study aimed to investigate the potential mechanisms of B. pseudolongum CCFM1253 on protecting against lipopolysaccharide (LPS)-induced acute liver injury (ALI) by metagenomic analysis and liver metabolomic profiles., Results: Bifidobacterium pseudolongum CCFM1253 preintervention remarkably attenuated the influence of LPS on serum alanine transaminase and aspartate amino transferase activities. B. pseudolongum CCFM1253 preintervention remarkably attenuated the inflammation responses (tumor necrosis factor-α, interleukin-1β, and interleukin-6) and elevated antioxidative enzymes activities [total antioxidant capacity, superoxide dismutase, catalase, and glutathione peroxidase] in ALI mice by intervening in the Nf-kβ and Nrf2 pathways, respectively. Bifidobacterium pseudolongum CCFM1253 treatment elevated the proportion of Alistipes and Bifidobacterium, and decreased the proportion of uncultured Bacteroidales bacterium, Muribaculum, Parasutterella and Ruminococcaceae UCG-010 in ALI mice, which were strongly correlated with the inhibition of inflammation responses and oxidative stress. Untargeted liver metabolomics exhibited that the hepatoprotective efficacy of B. pseudolongum CCFM1253 might be achieved by altering liver metabolites-related riboflavin metabolism, phenylalanine metabolism, alanine, citrate cycle (tricarboxylic acid cycle), and so on. Furthermore, riboflavin exposure could control the contents of malondialdehyde, superoxide dismutase, and catalase in hydrogen peroxide-treated HepG2 cells., Conclusion: Bifidobacterium pseudolongum CCFM1253 can effectively alleviate inflammatory response and oxidative stress, and regulate the intestinal microbiota composition and liver metabolism, and elevate the liver riboflavin content in LPS-treated mice. Therefore, B. pseudolongum CCFM1253 could serves as a potential probiotic to ameliorate the host health. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Short peptides have gained widespread utilization as functional constituents in the development of functional foods due to their remarkable biological activity. Previous investigations have established the positive influence of oysters on testosterone biosynthesis, although the underlying mechanism remains elusive. This study aims to assess the impact of three dipeptides derived from oysters on the oxidative stress state of TM3 cells induced by AAPH while concurrently examining alterations in cellular testosterone biosynthesis capacity. The investigation encompasses an analysis of reactive oxygen species (ROS) content, antioxidant enzyme activity, apoptotic status, and expression levels of crucial enzymes involved in the testosterone synthesis pathway within TM3 cells, thus evaluating the physiological activity of the three dipeptides. Additionally, molecular docking was employed to investigate the inhibitory activity of the three dipeptides against ACE. The outcomes of this study imply that the oxidative stress state of cells impedes the synthesis of testosterone by inhibiting the expression of essential proteins in the testosterone synthesis pathway. These three dipeptides derived from oysters ameliorate cellular oxidative stress by directly scavenging excess ROS or reducing ROS production rather than enhancing cellular antioxidant capacity through modulation of antioxidant enzyme activity. These findings introduce a novel avenue for developing and utilizing antioxidant peptides derived from food sources., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Nowadays, the biological activity of collagen peptides has been revealed, but the effect of Atlantic salmon (Salmo salar) bone-derived collagen peptide (CPs) on osteoarthritis remains unclear. In this study, CPs was identified as a small molecular weight peptide rich in Gly-X-Y structure. Meanwhile, interleukin-1β (IL-1β)-induced hypertrophic chondrocytes and partial medial meniscectomy (pMMx) surgery model in rats were performed. In IL-1β stimulated chondrocytes, CPs significantly increased the type-II collagen content, reduced the type-X collagen abundance and chondrocytes apoptosis. Meanwhile, CPs reversed the increased expression of matrix metalloproteinase, metalloproteinase with thrombospondin motifs and RUNX family transcription factor 2 in chondrocytes induced by IL-1β. In vivo, CPs increased pain tolerance of rats and without organ toxicity at 1.6 g/kg.bw. CPs significantly decreased the levels of COMP and Helix-II in serum. Furthermore, a significant decrease of IL-1β in synovial fluid and cartilage tissue were observed by CPs intervention. From Micro-CT, CPs (0.8 g/kg.bw) significantly decreased Tb.sp and SMI value. Meanwhile, the expression of tumor necrosis factor and interleukin-6 were reduced by CPs administration both in vitro and in vivo. Together, CPs showed potential to be a novel and safe dietary supplement for helping anti-inflammatory and cartilage regeneration, ultimately hindering osteoarthritis development. However, the clear mechanism of CPs's positive effect on osteoarthritis needs to be further explored., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Developing an effective universal influenza vaccine against influenza virus with highly conserved antigenic epitopes could induce a broad-spectrum immune response to prevent infection. The soluble protein M1 that can induce the M1 specific immune response was first confirmed in our previous study. In this study, we characterized the immune response induced by DNA prime-subunit protein boost strategy based on the relatively conserved matrix protein 1 (M1) in the BALB/c mouse model, and evaluated its protection ability against a lethal challenge of homologous H9N2 avian influenza virus (A/Chicken/Jiangsu/11/2002). The results showed that 100 μg DNA prime + 100 μg M1 subunit protein boost-strategy significantly increased antibody levels more than vaccination with M1 DNA or M1 subunit protein alone, and induced a more balanced Th1 / Th2 immune response, which not only can provide protection against the homologous virus but also can provide part of the cross-protection against the heterosubtypic PR8 H1N1 strain. In addition, we used an Elispot assay to preliminary screen the T cell epitope in M1 protein, and identified that p22 (M1 11-25 VLSIIPSGPLKAEIA) epitope was the only immunodominant M1-specific CD4 + T cell epitopes, which could be helpful in understanding the function of influenza virus T cell epitopes.

The miRNA-based strategy has been used to develop live attenuated influenza vaccines. In this study, the nucleoprotein (NP) genome segment of the influenza virus was inserted by different perfect miRNA-192-5p target sites, and the virus was rescued by standard reverse genetics method, so as to verify the virulence and protective efficacy of live attenuated vaccine in cells and mice. The results showed there was no significant attenuation in 192t virus with one perfect miRNA-192-5p target site, and 192t-3 virus with three perfect miRNA target sites. However, 192t-6 virus with 6 perfect miRNA target sites and 192t-9 virus with 9 perfect miRNA target sites were both significantly attenuated after infection, and their virulence were similar to that of temperature-sensitive (TS) influenza A virus (IAV) which is a temperature-sensitive live attenuated influenza vaccine. Mice were immunized with different doses of 192t-6, 192t-9, and TS IAV. Four weeks after immunization, the IgG in serum and IgA in lung homogenate were increased in the 192t-6, 192t-9, and TS IAV groups, and the numbers of IFN-γ secreting splenocytes were also increased in a dose-dependent manner. Finally, 192t-6, and 192t-9 can protect the mice against the challenge of homologous PR8 H1N1 virus and heterosubtypic H3N2 influenza virus. MiRNA targeted viruses 192t-6 and 192t-9 were significantly attenuated and showed the same virulence as TS IAV and played a role in the cross-protection.

Water-Cu(110) interaction is of particular importance during the routine use of graphene-based devices. In this work, water adsorption, dissociation, and desorption at elevated temperatures have been well studied using the time-of-flight ion scattering technique. It is found that water adsorption meets the first-order Langmuir adsorption model at room temperature. The variation of the ratio between residual O and H on the surface with temperature has been well determined, which profoundly reveals the dynamical process of surface composition. Furthermore, the change in the surface electronic properties has been probed by measuring negative-ion fractions as a function of the annealing temperature for fast ion scattering. It suggests that charge transfer is a very sensitive method for studying specific electronic processes in real time.

The dependence of the negative-ion fractions on incident energy and angle is reported for 8.5-22.5 keV F(-) ions scattered from a Si(100) surface at a fixed scattering angle of 38°. The negative-ion fraction increases monotonically with incident velocity for specular scattering. In particular, the variation of the fraction with incident angle is bell shaped for a given incident energy. We interpret this variation using the incident-velocity effect at short distances where the yield of negative ions depends on the number of initial neutrals. It strongly indicates that at short distances, a dynamical equilibrium population is never achieved. This nonadiabatic feature is supported by simple calculations using modified rate equations.

Highly pathogenic avian influenza (HPAI) H5N1 virus infection is still a potential threat to public health worldwide. While vaccines and antiviral drugs are currently under development, neutralizing antibodies could offer an alternative strategy to prevent and treat H5N1 virus infection. In the present study, we had developed a humanized antibody against H5N1 viruses from mouse-derived hybridoma in order to minimize its immunogenicity for potential clinical application. The humanized antibody hH5M9 was generated by transferring the mouse complementarity determining region (CDR) residues together with four key framework region (FR) residues onto the FR of the human antibody. This humanized antibody exhibited high affinity and specificity comparable to the parental mouse or chimeric counterpart with broad and strong neutralization activity against all H5N1 clades and subclades except for Egypt clades investigated. Furthermore, through epitope mapping we identified a linear epitope on the top region of hemagglutinin (HA) that was H5N1 specific and conserved. Our results for the first time reported a humanized antibody against H5N1 viruses by CDR grafting method. With the expected lower immunogenicity, this humanized antibody was expected to be more efficacious than murine or human-mouse chimeric antibodies for future application in humans.