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Simple Summary: In the present meta-analysis of randomized controlled trials, probiotic fermented milk supplementation appeared to be beneficial in lowering the levels of fasting plasma glucose, HbA1c, total cholesterol, and C-reactive protein. While these findings are encouraging, they should be interpreted cautiously, as considerable limitations of the included trials and analyses precluded solid conclusions. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (M111–25 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. [ABSTRACT FROM AUTHOR]

This paper presents extended techniques aiming at the improvement of automatic speech recognition (ASR) in single-channel scenarios in the context of the REVERB (REverberant Voice Enhancement and Recognition Benchmark) challenge. The focus is laid on the development and analysis of ASR front-end technologies covering speech enhancement and feature extraction. Speech enhancement is performed using a joint noise reduction and dereverberation system in the spectral domain based on estimates of the noise and late reverberation power spectral densities (PSDs). To obtain reliable estimates of the PSDs-even in acoustic conditions with positive direct-to-reverberation energy ratios (DRRs)-we adopt the statistical model of the room impulse response explicitly incorporating DRRs, as well in combination with a novel proposed joint estimator for the reverberation time T and the DRR. The feature extraction approach is inspired by processing strategies of the auditory system, where an amplitude modulation filterbank is applied to extract the temporal modulation information. These techniques were shown to improve the REVERB baseline in our previous work. Here, we investigate if similar improvements are obtained when using a state-of-the-art ASR framework, and to what extent the results depend on the specific architecture of the back-end. Apart from conventional Gaussian mixture model (GMM)-hidden Markov model (HMM) back-ends, we consider subspace GMM (SGMM)-HMMs as well as deep neural networks in a hybrid system. The speech enhancement algorithm is found to be helpful in almost all conditions, with the exception of deep learning systems in matched training-test conditions. The auditory feature type improves the baseline for all system architectures. The relative word error rate reduction achieved by combining our front-end techniques with current back-ends is 52.7% on average with the REVERB evaluation test set compared to our original REVERB result. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Metastasis of lung cancer is an important factor affecting survival. The present study proposed to establish and verify a nomogram for predicting overall survival (OS) in lung adenocarcinoma (LUAD) patients with different patterns of metastasis. Methods: A total of 9727 patients diagnosed with metastatic LUAD patients from 2010 to 2015 were enrolled based on surveillance, epidemiology and end results (SEER) Database and then randomly divided into training and validation cohorts, and 136 patients in our Cancer Center were enrolled as the external validation cohort. Univariate and multivariate analyses were performed to evaluate the prognostic impact on OS. A prognostic nomogram was constructed and evaluated by C-index, calibration curve, decision curve analysis (DCA), and risk stratification system. Results: Ultimately, 6809 and 2918 patients diagnosed with metastatic LUAD in the training and validation cohorts were enrolled in the study, respectively. A male sex, a later T and N stage, a larger tumor size, treatment including no surgery, no chemotherapy and no radiotherapy, metastasis sites were found to be independent risk factors in LUAD patients for worse OS, and then incorporated into the nomogram. The frequency of bone metastasis was the highest, and in single site metastasis, the prognosis of liver metastasis was the worst. Two-site metastasis is more common than three-site and four-site metastasis, and co-metastasis eventually leads to a worse survival outcome. The C-index value of nomogram for predicting OS were 0.798, 0.703 and 0.698 in the internal training, validation and external validation cohorts, separately. The calibration curves for the 6-months, 1-year and 2-year showed significant agreement between nomogram models and actual observations. The DCA curves indicated nomogram was more beneficial than the AJCC TNM stage. Patients were further divided into low-risk and high-risk groups according to nomogram predicted scores and developed a survival risk classification system. Conclusions: Our prognostic nomogram is expected to be an accurate and individualized clinical predictive tool for predicting OS in LUAD patients with different patterns of metastasis. [ABSTRACT FROM AUTHOR]

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In this paper, we discuss stochastic comparisons of parallel systems with scale proportional hazards components equipped with starting devices. To begin with, we present the hazard rate order of parallel systems with two scale proportional hazards components equipped with starting devices for two different cases: first when the starting devices with different probability have the same scale proportional hazards components, and the second when the different scale proportional hazards components have the same starting devices probability. Next, we present the usual stochastic order of parallel systems with scale proportional hazards components equipped with starting devices. Finally, we provide some numerical examples to illustrate all the results established here. [ABSTRACT FROM AUTHOR]

In this paper, a memristive circuit system is proposed and its dynamical characteristics are analyzed by two-parameters bifurcation diagrams, Lyapunov exponent spectrum, SE complexity and C0 complexity. The numerical analysis results illustrate that the chaotic state of the memristive system is distributed in a large range of parameters, which is especially suitable for image encryption application. Then, in view of the fact that the traditional method of observing three-dimensional chaotic attractors can not give full play to the essence of human eyes cooperating with brain information processing, a new method to obtain the brain information of complete three-dimensional chaotic attractors by using red–blue 3D glasses is proposed. The results show that compared with the traditional method based on the memristive system, the visual effect of chaotic attractors observed by red–blue 3D glasses is shocking. In addition, an image encryption algorithm is designed to verify the image encryption application of the memristive system based on DNA variation. A series of security performance analysis experiments are performed to verify the effectiveness and reliability of the designed algorithm such as the secret key space analysis, histogram distribution analysis, information entropy analysis, correlation analysis and key sensitivity analysis. Finally, the hardware circuit based on the memristive system is implemented with some common electronic devices, which has the advantages of simple structure and low cost. [ABSTRACT FROM AUTHOR]

We hypothesize that short selling has a disciplining role vis-à-vis firm managers that forces them to reduce earnings management. Using firm-level short-selling data for thirty-three countries collected over a sample period from 2002 to 2009, we document a significantly negative relationship between the threat of short selling and earnings management. Tests based on instrumental variable and exogenous regulatory experiments offer evidence of a causal link between short selling and earnings management. Our findings suggest that short selling functions as an external governance mechanism to discipline managers. [ABSTRACT FROM AUTHOR]