Inhibiting Aspergillus flavus growth and degrading aflatoxin B1 by combined beneficial microbes

Aflatoxin B1 (AFB1) is a type of toxin produced by Aspergillus flavus, which has a negative effect on animal production and economic profits. In order to inhibit A. flavus growth and degrade aflatoxin, the optimal  proportion of beneficial microbes such as Lactobacillus casei, Bacillus subtilis and Pichia anomala were selected. The results show that AFB1 production and mycelium weight of A. flavus was decreased by more than 34 folds (161.05 vs. 4.69 µ/L) and 7.7 folds (6.98 vs. 0.90 mg/ml) with the free-cell supernatants of L. casei and B. subtilis (P<0.05), respectively. The optimal proportion of L. casei, B. subtilis and P. anomala was 2:1:2 for inhibiting A. flavus growth determined by 3x3 orthogonal design. Based on the optimal proportion of three microbial species, the maximum AFB1 degradation was during 24 to 48 h incubation (P<0.05). When three species of beneficial microbes were mixed with yeast cell wall and oligosaccharide, both of them could not help the microbes in AFB1 degradation. The combined microbial incubation showed that AFB1 contents in the supernatant and cells were 10.25 (P<0.05) and 3.34 µg/L, lower than the control group (68.55 µg/L), indicating that most of the AFB1 were degraded by the microbes and only a little of them were absorbed and deposited in microbial cells.Key words: Aspergillus flavus, aflatoxin B1 detoxification, beneficial microbes, yeast cell wall, oligosaccharide

Integrated network analysis and metabolomics reveal the molecular mechanism of Yinchen Sini decoction in CCl4-induced acute liver injury

Objective: Yinchen Sini decoction (YCSND), a traditional Chinese medicine (TCM) formula, plays a crucial role in the treatment of liver disease. However, the bioactive constituents and pharmacological mechanisms of action remain unclear. The present study aimed to reveal the molecular mechanism of YCSND in the treatment of acute liver injury (ALI) using integrated network analysis and metabolomics.Methods: Ultra-high-performance liquid chromatography coupled with Q-Exactive focus mass spectrum (UHPLC-QE-MS) was utilized to identify metabolites in YCSND, and high-performance liquid chromatography (HPLC) was applied to evaluate the quality of four botanical drugs in YCSND. Cell damage and ALI models in mice were established using CCl4. 1H-NMR metabolomics approach, along with histopathological observation using hematoxylin and eosin (H&E), biochemical measurements, and reverse transcription quantitative real-time PCR (RT-qPCR), was applied to evaluate the effect of YCSND on CCl4- induced ALI. Network analysis was conducted to predict the potential targets of YCSND in ALI.Result: Our results showed that 89 metabolites in YCSND were identified using UHPLC-QE-MS. YCSND protected against ALI by reducing the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) contents and increasing those of superoxide dismutase (SOD), and glutathione (GSH) both in vivo and in vitro. The 1H-NMRmetabolic pattern revealed that YCSND reversed CCl4-induced metabolic abnormalities in the liver. Additionally, the Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis identified five pathways related to liver injury, including the PI3K-AKT, MAPK, HIF-1, apoptosis, and TNF signaling pathways. Moreover, RT-qPCR showed YCSND regulated the inflammatory response (Tlr4, Il6, Tnfα, Nfκb1, Ptgs2, and Mmp9) and apoptosis (Bcl2, Caspase3, Bax, and Mapk3), and inhibited PI3K-AKT signaling pathway (Pi3k and Akt1). Combined network analysis and metabolomics showed a link between the key targets (Tlr4, Ptgs2, and Mmp9) and vital metabolites (choline, xanthine, lactate, and 3-hydroxybutyric acid) of YCSND in ALI.Conclusion: Overall, the results contribute to the understanding of the therapeutic effects of YCSND on ALI, and indicate that the integrated network analysis and metabolomics could be a powerful strategy to reveal the pharmacological effects of TCM

Clinical Findings in Patients With Persistent Positional Nystagmus: The Designation of “Heavy and Light Cupula”

Objective: Direction-changing positional nystagmus (DCPN) had been observed as persistent horizontal apogeotropic and was considered as “cupulolithiasis or heavy cupula. ” Recently, the concept of “light cupula” exhibiting persistent geotropic DCPN has been introduced. However, the light cupula is not systematically described, while the identification and diagnosis of “light cupula” should be improved. Here we investigated the underlying characteristics and therapeutic options designed to the “light” and “heavy” cupula, respectively; and summarized the clinical characteristics and therapeutic effect in the two groups.Methods: A total of 359 cases with vertigo and bilateral DCPN were found in the supine roll test. Only 25 patients with persistent DCPN were enrolled and followed up. According to the direction of nystagmus, we further divided the patients into “heavy cupula” (apogeotropic) and “light cupula” (geotropic) groups. We compared the incidence, characteristics of nystagmus and the efficacy of repositioning maneuver in the two groups.Results: Nine patients with persistent horizontal geotropic DCPN were confirmed as “light cupula,” other 16 patients with persistent horizontal ageotropic DCPN were confirmed as heavy cupula. All 25 patients had null plane; the mean value and standard deviation of the null plane in light cupula and heavy cupula was 25.67 ± 9.31° and 27.06 ± 6.29°, respectively. The mean value and standard deviation of the termination plane in light cupula was 28.78 ± 10.00°, and 30.25 ± 6.53° in heavy cupula. There was no statistical significance between the two groups. We found that the direction of evoked nystagmus in the supine position was toward the intact side in light cupula, while in heavy cupula, it was toward the lesion side. The null plane appeared on the lesion side. For light cupula patients, the effect was not obvious at Day-7 after the treatment, however, treatment for most heavy cupula patients were effective. All patients recovered after 30 days of treatment.Conclusion: The null plane is crucial in determining the lesion side for light or heavy cupula. Although the short-term therapeutic effect of the light cupula is not as promising as the effect seen in heavy cupula, the long-term prognosis in both groups is comparable; with all patients recovered after 30 days of treatment.Study design: This is a retrospective cohort study

Panel 3 : Genetics and Precision Medicine of Otitis Media

Objective. The objective is to perform a comprehensive review of the literature up to 2015 on the genetics and precision medicine relevant to otitis media. Data Sources. PubMed database of the National Library of Medicine. Review Methods. Two subpanels were formed comprising experts in the genetics and precision medicine of otitis media. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a merged draft was created. The entire panel met at the 18th International Symposium on Recent Advances in Otitis Media in June 2015 and discussed the review and refined the content. A final draft was made, circulated, and approved by the panel members. Conclusion. Many genes relevant to otitis media have been identified in the last 4 years in advancing our knowledge regarding the predisposition of the middle ear mucosa to commensals and pathogens. Advances include mutant animal models and clinical studies. Many signaling pathways are involved in the predisposition of otitis media. Implications for Practice. New knowledge on the genetic background relevant to otitis media forms a basis of novel potential interventions, including potential new ways to treat otitis media.Peer reviewe

GradAuto:Energy-oriented Attack on Dynamic Neural Networks

Dynamic neural networks could adapt their structures or parameters based on different inputs. By reducing the computation redundancy for certain samples, it can greatly improve the computational efficiency without compromising the accuracy. In this paper, we investigate the robustness of dynamic neural networks against energy-oriented attacks. We present a novel algorithm, named GradAuto, to attack both dynamic depth and dynamic width models, where dynamic depth networks reduce redundant computation by skipping some intermediate layers while dynamic width networks adaptively activate a subset of neurons in each layer. Our GradAuto carefully adjusts the direction and the magnitude of the gradients to efficiently find an almost imperceptible perturbation for each input, which will activate more computation units during inference. In this way, GradAuto effectively boosts the computational cost of models with dynamic architectures. Compared to previous energy-oriented attack techniques, GradAuto obtains the state-of-the-art result and recovers 100% dynamic network reduced FLOPs on average for both dynamic depth and dynamic width models. Furthermore, we demonstrate that GradAuto offers us great control over the attacking process and could serve as one of the keys to unlock the potential of the energy-oriented attack. Please visit https://github.com/JianhongPan/GradAuto for code

A 13-Gene Metabolic Prognostic Signature Is Associated With Clinical and Immune Features in Stomach Adenocarcinoma

Patients with advanced stomach adenocarcinoma (STAD) commonly show high mortality and poor prognosis. Increasing evidence has suggested that basic metabolic changes may promote the growth and aggressiveness of STAD; therefore, identification of metabolic prognostic signatures in STAD would be meaningful. An integrative analysis was performed with 407 samples from The Cancer Genome Atlas (TCGA) and 433 samples from Gene Expression Omnibus (GEO) to develop a metabolic prognostic signature associated with clinical and immune features in STAD using Cox regression analysis and least absolute shrinkage and selection operator (LASSO). The different proportions of immune cells and differentially expressed immune-related genes (DEIRGs) between high- and low-risk score groups based on the metabolic prognostic signature were evaluated to describe the association of cancer metabolism and immune response in STAD. A total of 883 metabolism-related genes in both TCGA and GEO databases were analyzed to obtain 184 differentially expressed metabolism-related genes (DEMRGs) between tumor and normal tissues. A 13-gene metabolic signature (GSTA2, POLD3, GLA, GGT5, DCK, CKMT2, ASAH1, OPLAH, ME1, ACYP1, NNMT, POLR1A, and RDH12) was constructed for prognostic prediction of STAD. Sixteen survival-related DEMRGs were significantly related to the overall survival of STAD and the immune landscape in the tumor microenvironment. Univariate and multiple Cox regression analyses and the nomogram proved that a metabolism-based prognostic risk score (MPRS) could be an independent risk factor. More importantly, the results were mutually verified using TCGA and GEO data. This study provided a metabolism-related gene signature for prognostic prediction of STAD and explored the association between metabolism and the immune microenvironment for future research, thereby furthering the understanding of the crosstalk between different molecular mechanisms in human STAD. Some prognosis-related metabolic pathways have been revealed, and the survival of STAD patients could be predicted by a risk model based on these pathways, which could serve as prognostic markers in clinical practice

Estimation of Recurrence of Colorectal Adenomas with Dependent Censoring Using Weighted Logistic Regression

In colorectal polyp prevention trials, estimation of the rate of recurrence of adenomas at the end of the trial may be complicated by dependent censoring, that is, time to follow-up colonoscopy and dropout may be dependent on time to recurrence. Assuming that the auxiliary variables capture the dependence between recurrence and censoring times, we propose to fit two working models with the auxiliary variables as covariates to define risk groups and then extend an existing weighted logistic regression method for independent censoring to each risk group to accommodate potential dependent censoring. In a simulation study, we show that the proposed method results in both a gain in efficiency and reduction in bias for estimating the recurrence rate. We illustrate the methodology by analyzing a recurrent adenoma dataset from a colorectal polyp prevention trial

Sirtuin 1 and Autophagy Attenuate Cisplatin-Induced Hair Cell Death in the Mouse Cochlea and Zebrafish Lateral Line

Cisplatin-induced ototoxicity is one of the major adverse effects in cisplatin chemotherapy, and hearing protective approaches are unavailable in clinical practice. Recent work unveiled a critical role of autophagy in cell survival in various types of hearing loss. Since the excessive activation of autophagy can contribute to apoptotic cell death, whether the activation of autophagy increases or decreases the rate of cell death in CDDP ototoxicity is still being debated. In this study, we showed that CDDP induced activation of autophagy in the auditory cell HEI-OC1 at the early stage. We then used rapamycin, an autophagy activator, to increase the autophagy activity, and found that the cell death significantly decreased after CDDP injury. In contrast, treatment with the autophagy inhibitor 3-methyladenine (3-MA) significantly increased cell death. In accordance with in vitro results, rapamycin alleviated CDDP-induced death of hair cells in zebrafish lateral line and cochlear hair cells in mice. Notably, we found that CDDP-induced increase of Sirtuin 1 (SIRT1) in the HEI-OC1 cells modulated the autophagy function. The specific SIRT1 activator SRT1720 could successfully protect against CDDP-induced cell loss in HEI-OC1 cells, zebrafish lateral line, and mice cochlea. These findings suggest that SIRT1 and autophagy activation can be suggested as potential therapeutic strategies for the treatment of CDDP-induced ototoxicity

Discovery and Genomic Characterization of Noroviruses from a Gastroenteritis Outbreak in Domestic Cats in the US

Norovirus (NoV) RNA was detected in the stools of 6 out 14 (42.8%) 8–12-week-old cats with enteritis from a feline shelter, in New York State. Upon sequence analysis of the complete capsid, the six NoVs were found to be identical, suggesting the spread of a unique NoV strain in the shelter. The full-length genomic sequence (7839 nt) of one feline NoV, CU081210E/2010/US, was determined. In the capsid protein VP1 region, the virus displayed the highest amino acid identity to animal genogroup IV genotype 2 (GIV.2) NoVs: lion/Pistoia-387/06/IT (97.9%) and dog/Bari-170/07/IT (90.4%). These findings document the discovery of a novel feline calicivirus, different from vesiviruses, and extend the spectrum of NoV host range. Epidemiological studies using feline NoV-specific diagnostic tools and experimental infection of cats are required to understand whether NoVs have a pathogenic role in this species