A conserved protein inhibitor brings under check the activity of RNase E in cyanobacteria.

The bacterial ribonuclease RNase E plays a key role in RNA metabolism. Yet, with a large substrate spectrum and poor substrate specificity, its activity must be well controlled under different conditions. Only a few regulators of RNase E are known, limiting our understanding on posttranscriptional regulatory mechanisms in bacteria. Here we show that, RebA, a protein universally present in cyanobacteria, interacts with RNase E in the cyanobacterium Anabaena PCC 7120. Distinct from those known regulators of RNase E, RebA interacts with the catalytic region of RNase E, and suppresses the cleavage activities of RNase E for all tested substrates. Consistent with the inhibitory function of RebA on RNase E, depletion of RNase E and overproduction of RebA caused formation of elongated cells, whereas the absence of RebA and overproduction of RNase E resulted in a shorter-cell phenotype. We further showed that the morphological changes caused by altered levels of RNase E or RebA are dependent on their physical interaction. The action of RebA represents a new mechanism, potentially conserved in cyanobacteria, for RNase E regulation. Our findings provide insights into the regulation and the function of RNase E, and demonstrate the importance of balanced RNA metabolism in bacteria.

The level of serum retinol-binding protein is associated with diabetic mild cognitive impairment.

BACKGROUND: Several studies have shown that retinol-binding protein (RBP) is linked to diabetes and neurodegenerative diseases. However, no studies have elucidated the relationship between RBP and diabetic cognitive disorders. OBJECTIVE: To determine whether the change characteristics of serum RBP are associated with alterations in cognitive functioning in type 2 diabetes mellitus (T2DM). METHODS: In this study, 252 patients with T2DM and 34 people as healthy controls were included. According to the Montreal Cognitive Assessment (MoCA), the diabetic subjects were divided into the mild cognitive impairment (MCI) group and the Non-MCI group. Demographic characteristics and clinical indicators as well as serum RBP levels were analyzed. RESULTS: The serum RBP levels in the MCI group were lower compared with the Non-MCI group (P = 0.02). The level of RBP was higher in the diabetes without MCI group than in the healthy control (P < 0.001). Serum RBP levels were positively correlated with MoCA scores (r = 0.178, P = 0.003). Binary Logistic regression model analysis showed that low RBP [odds ratio (OR) = 0.936], old age (OR = 1.074), high fasting blood glucose (OR = 1.164), and low fasting C-peptide (OR = 0.722) may be independent risk factors for diabetic MCI. The ROC curve of serum RBP for predicting diabetic MCI showed that the area under the curve was 0.630. CONCLUSIONS: Our study revealed an association between serum RBP and diabetic MCI. Serum RBP levels in diabetic MCI are lower and correlated with cognitive function.

Application and interpretation of machine learning models in predicting the risk of severe obstructive sleep apnea in adults.

BACKGROUND: Obstructive sleep apnea (OSA) is a globally prevalent disease with a complex diagnostic method. Severe OSA is associated with multi-system dysfunction. We aimed to develop an interpretable machine learning (ML) model for predicting the risk of severe OSA and analyzing the risk factors based on clinical characteristics and questionnaires. METHODS: This was a retrospective study comprising 1656 subjects who presented and underwent polysomnography (PSG) between 2018 and 2021. A total of 23 variables were included, and after univariate analysis, 15 variables were selected for further preprocessing. Six types of classification models were used to evaluate the ability to predict severe OSA, namely logistic regression (LR), gradient boosting machine (GBM), extreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), bootstrapped aggregating (Bagging), and multilayer perceptron (MLP). All models used the area under the receiver operating characteristic curve (AUC) was calculated as the performance metric. We also drew SHapley Additive exPlanations (SHAP) plots to interpret predictive results and to analyze the relative importance of risk factors. An online calculator was developed to estimate the risk of severe OSA in individuals. RESULTS: Among the enrolled subjects, 61.47% (1018/1656) were diagnosed with severe OSA. Multivariate LR analysis showed that 10 of 23 variables were independent risk factors for severe OSA. The GBM model showed the best performance (AUC = 0.857, accuracy = 0.766, sensitivity = 0.798, specificity = 0.734). An online calculator was developed to estimate the risk of severe OSA based on the GBM model. Finally, waist circumference, neck circumference, the Epworth Sleepiness Scale, age, and the Berlin questionnaire were revealed by the SHAP plot as the top five critical variables contributing to the diagnosis of severe OSA. Additionally, two typical cases were analyzed to interpret the contribution of each variable to the outcome prediction in a single patient. CONCLUSIONS: We established six risk prediction models for severe OSA using ML algorithms. Among them, the GBM model performed best. The model facilitates individualized assessment and further clinical strategies for patients with suspected severe OSA. This will help to identify patients with severe OSA as early as possible and ensure their timely treatment. TRIAL REGISTRATION: Retrospectively registered.

α-Aminobutyric Acid Constrains Macrophage-Associated Inflammatory Diseases through Metabolic Reprogramming and Epigenetic Modification.

Metabolites play critical roles in macrophage polarization and in their function in response to infection and inflammation. α-aminobutyric acid (AABA), a non-proteinogenic amino acid which can be generated from methionine, threonine, serine, and glycine, has not been studied extensively in relation to macrophage polarization and function. In this study, we aimed to investigate the immunomodulatory function of AABA in regulating M1 macrophage polarization and function in vitro and in vivo. We stimulated bone-marrow-derived macrophages with lipopolysaccharide (LPS) to generate M1 macrophages. Subsequently, we induced sepsis and colitis in mice, followed by treatment with AABA. We then analyzed the samples using ELISA, real-time PCR, Western blotting, flow cytometry, and histopathological analysis to evaluate cytokine secretion, inflammatory gene expression, macrophage activation, disease progression, and inflammation severity. Additionally, metabolomic and chromatin immunoprecipitation-qPCR were conducted to investigate the function of AABA on metabolic reprogramming and epigenetic modifications of M1 macrophages. Our results revealed that AABA inhibited M1 macrophage polarization and function, which led to prolonged survival in septic mice and reduced disease severity in colitis mice. Mechanically, AABA promoted oxidative phosphorylation (OXPHOS) and glutamine and arginine metabolism while inhibiting glycolysis. Moreover, AABA could increase the occupancy of trimethylation of histone H3K27 at the promoter regions of M1 macrophage-associated inflammatory genes, which contributed to the inhibition of M1 macrophage polarization. These findings suggest that AABA may have therapeutic potential for inflammatory diseases by regulating macrophage polarization and function through metabolic and epigenetic pathways.

Association between obstructive sleep apnea and thyroid function: A 10-year retrospective study.

PURPOSE: To explore whether the obstructive sleep apnea (OSA) has an impact on thyroid function in patients. METHOD: The data of 853 patients were retrospectively collected from the Second Affiliated Hospital of Xi'an Jiaotong University in recent ten years. All the objects were divided into the control group, mild-moderate and severe OSA groups according to the result of polysomnography. RESULTS: In the non-elderly population (age <60), there were significant differences in serum free triiodothyronine (FT3) and total triiodothyronine (TT3) between the mild-moderate and severe OSA groups (all p < 0.05). And there were differences in serum total thyroxine, anti-thyroid peroxidase, and antithyroglobulin between the control and mild-moderate OSA groups (all p < 0.05). Moreover, FT3 was associated with age (OR = 0.98, p < 0.05) and apnea-hypopnea index (OR = 1.01, p < 0.05). The occurrence of thyroid nodules was associated with average transcutaneous oxygen saturation (Mean SaO2) (OR = 0.97, p < 0.05). In the elderly (age ≥60), there was no difference in FT3 and TT3 between the mild-moderate and severe OSA. While the occurrence of thyroid nodules was also associated with Mean SaO2 (OR = 0.90, p < 0.05). CONCLUSION: In the non-elderly population, the progress of OSA may promote the increase in thyroid hormone (especially FT3) levels, while in the elderly population not. In the whole age population, Mean SaO 2 is associated with the occurrence of thyroid nodules. Future research on the relationship between OSA and thyroid function, and age stratification is necessary.

Characterization and modelling of odor-active compounds release behavior from Fu-brick tea during boiling-water extraction by molecular sensory science approach.

The odor-active compounds in Fu-brick tea and their release behaviors during boiling-water were studied. Fifty-one odor-active compounds were identified, and their release behaviors were identified by continuously recovering 16 sections of condensed water combined with sensory, instrumental, and nonlinear curve fitting analysis. The odor intensities of condensed water and the concentrations of odor-active compounds could be significantly fitted (p < 0.01) to power-function type curves. Hydrocarbons showed the fastest release rate, while organic acids showed the slowest. The release rates had very little correlation with their concentrations, molecular weights, and boiling points. Most odor-active compounds (≥70 %) released need to evaporate more than 24 % of the added water during boiling-water extraction. Meanwhile, on the basis of odor activity value (OAV) calculation, the aroma recombination experiments were performed to explore the odor-active compounds that made major contributions to the formation of the aroma profile of each condensed water.

[The application of waterless empirical taste test（WETT®ï¼‰ in 159 Chinese healthy subjects].

Objective:This study examined the influences of age and gender on the taste function of a sizable sample of healthy Chinese subjects using the Waterless Empirical Taste Test（WETT®ï¼‰, and provided scientific evidences for taste evaluation in clinic. Methods:A total of 159 subjects were tested based on strict inclusion and exclusion criteria. The 53 stimuli strips, presented on monomer cellulose pads, were designed to test 5 basic taste functions including sour, sweet, bitter, salty and umami of all subjects. The analysis was computed in SAS 9.4 statistical software. Results:The total taste score of the subjects was 35.00±8.94; the average test administration time was（21.61±7.80） min. The total test scores decreased across age categories（young group: 37.41±8.12, middle-aged group: 34.48±9.04, elderly group: 29.31±8.64）, the correlation coefficient between the total test scores and age was r=-0.335, P<0.05. There were significant differences in sour and bitter scores among different age groups（Psour=0.019, Pbitter<0.001）. Overall, women outperformed men on the total test（[36.53±8.72]vs[32.93±8.87], P=0.012）. There were correlations among individual taste of scores, and the correlation coefficient between umami and total score was the strongest（rumami/total=0.700，P<0.05）. Conclusion:This study demonstrated that a simple self-administered taste test, the WETT®, could be applied to Chinese healthy people. Age and gender-effects are the main factors which affect gustatory function.

Prediction model of obstructive sleep apnea-related hypertension: Machine learning-based development and interpretation study.

Background: Obstructive sleep apnea (OSA) is a globally prevalent disease closely associated with hypertension. To date, no predictive model for OSA-related hypertension has been established. We aimed to use machine learning (ML) to construct a model to analyze risk factors and predict OSA-related hypertension. Materials and methods: We retrospectively collected the clinical data of OSA patients diagnosed by polysomnography from October 2019 to December 2021 and randomly divided them into training and validation sets. A total of 1,493 OSA patients with 27 variables were included. Independent risk factors for the risk of OSA-related hypertension were screened by the multifactorial logistic regression models. Six ML algorithms, including the logistic regression (LR), the gradient boosting machine (GBM), the extreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), bootstrapped aggregating (Bagging), and the multilayer perceptron (MLP), were used to develop the model on the training set. The validation set was used to tune the model hyperparameters to determine the final prediction model. We compared the accuracy and discrimination of the models to identify the best machine learning algorithm for predicting OSA-related hypertension. In addition, a web-based tool was developed to promote its clinical application. We used permutation importance and Shapley additive explanations (SHAP) to determine the importance of the selected features and interpret the ML models. Results: A total of 18 variables were selected for the models. The GBM model achieved the most extraordinary discriminatory ability (area under the receiver operating characteristic curve = 0.873, accuracy = 0.885, sensitivity = 0.713), and on the basis of this model, an online tool was built to help clinicians optimize OSA-related hypertension patient diagnosis. Finally, age, family history of hypertension, minimum arterial oxygen saturation, body mass index, and percentage of time of SaO2 < 90% were revealed by the SHAP method as the top five critical variables contributing to the diagnosis of OSA-related hypertension. Conclusion: We established a risk prediction model for OSA-related hypertension patients using the ML method and demonstrated that among the six ML models, the gradient boosting machine model performs best. This prediction model could help to identify high-risk OSA-related hypertension patients, provide early and individualized diagnoses and treatment plans, protect patients from the serious consequences of OSA-related hypertension, and minimize the burden on society.

NLRP3 inflammasome regulates astrocyte transformation in brain injury induced by chronic intermittent hypoxia.

BACKGROUND: Obstructive sleep apnea (OSA) is mainly characterized by sleep fragmentation and chronic intermittent hypoxia (CIH), the latter one being associated with multiple organ injury. Recently, OSA-induced cognition dysfunction has received extensive attention from scholars. Astrocytes are essential in neurocognitive deficits via A1/A2 phenotypic changes. Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is considered the most important factor inducing and maintaining neuroinflammation. However, whether the NLRP3 regulates the A1/A2 transformation of astrocytes in CIH-related brain injury remains unclear. METHODS: We constructed an OSA-related CIH animal model and assessed the rats' learning ability in the Morris water maze; the histopathological assessment was performed by HE and Nissl staining. The expression of GFAP (astrocyte marker), C3d (A1-type astrocyte marker), and S100a10 (A2-type astrocyte marker) were detected by immunohistochemistry and immunofluorescence. Western blotting and RT-qPCR were used to evaluate the changes of A1/A2 astrocyte-related protein and NLRP3/Caspase-1/ASC/IL-1ß. RESULTS: The learning ability of rats decreased under CIH. Further pathological examination revealed that the neurocyte in the hippocampus were damaged. The cell nuclei were fragmented and dissolved, and Nissl bodies were reduced. Immunohistochemistry showed that astrocytes were activated, and morphology and number of astrocytes changed. Immunofluorescence, Western blotting and RT-qPCR showed that the expression of C3d was increased while S100a10 was decreased. Also, the expression of the inflammasome (NLRP3/Caspase-1/ASC/IL-1ß) was increased. After treatment of MCC950 (a small molecule inhibitor of NLRP3), the damage of nerve cells was alleviated, the Nissl bodies increased, the activation of astrocytes was reduced, and the expression of A2-type astrocytes was increased. In contrast, A1-type astrocytes decreased, and the expression of inflammasome NLRP3/Caspase-1/ASC/IL-1ß pathway-related proteins decreased. CONCLUSION: The NLRP3 inflammasome could regulate the A1/A2 transformation of astrocytes in brain injury induced by CIH.

Etiology distribution of abnormal uterine bleeding according to FIGO classification system: A combined study of ultrasound and histopathology.

AIM: To classify the FIGO's PALM-COEIN etiology for abnormal uterine bleeding (AUB) patients according to the ultrasound and histopathology and to evaluate the etiology prevalence distribution for AUB patients. METHODS: A total of 1065 women with AUB in the Second Hospital of Shandong University between January 2019 and March 2021. The intrauterine histopathological and ultrasound results were reviewed retrospectively.PALM-COEIN etiology classification was performed according to histopathology and ultrasound. The classification system was stratified into nine basic categories: Polyp (AUB-P), adenomyosis (AUB-A), leiomyoma (AUB-L), malignancy and hyperplasia (AUB-M), coagulopathy (AUB-C), ovulatory disorders (AUB-O), endometrium (AUB-E), Iatrogenic(AUB-I), and not classified (AUB-N). The number of cases and composition ratio were also calculated. RESULTS: According to the FIGO's classification system, the PALM group (656,61.60%), which were defined as structural entities that can be measured visually with ultrasound and/or histopathology. 176 (16.53%) patients were classified as AUB-P,102 (9.58%) patients were classified as AUB-A, 487(45.73%) patients were classified as AUB-L, 31 (2.91%) patients were classified as AUB-M. The COEIN group (409,38.40%), which were defined as nonstructural entities that cannot be measured by ultrasound and/or histopathology. Nobody were classified as AUB-C in our group, and 383 (35.96%) patients were classified as AUB-O, 4 (0.38%) patients were classified as AUB-E,14 (1.31%) patients were classified as AUB-I,8 (0.75%) patients were classified as AUB-N. CONCLUSION: In our study, AUB-L was the most common cause, followed by AUB-O, AUB-P, AUB-A, AUB-M, AUB-I, AUB-N, and AUB-E.PALM-COEIN etiology classification system played an important role in the epidemic and management standardization of AUB patients, provided an effective communication between physicians and researchers also. Ultrasonography was the preferred examination for AUB patients, especially with structural abnormalities.

[Arousal characteristics in different OSAHS populations].

Objective:This study sought to explore the effect of age on arousal index in patients with OSAHS, and the significance of arousal index among different phenotypes identified through cluster analysis according to clinical symptoms and complications. Methods:A total of 607 adult patients with OSAHS who received polysomnography in the Second Affiliated Hospital of Xi'an Jiaotong University from July 2020 to July 2021 were selected. All patients registered basic human data, symptoms, complaints and complications, completed the Epworth Sleepiness Scale. We explored the distribution of several PSG parameters in different age groups, and included typical symptoms and complications into cluster analysis to explore the parameter differences in patients with different phenotypes. Results:Young patients had the lowest arousal index and arousal frequency in NREM stage, in middle-aged patients, the arousal index was relatively higher, the arousal times during NREM with oxygen desaturation were the highest. Among elderly patients, the wakefulness after sleep onset（WASO） was the longest, the arousal times in REM sleep was the lowest, and the spontaneous arousal times in NREM sleep were the highest（P<0.05）. Among the 3 types according to the cluster analysis, phenotype Ⅰwas characterised by maximally complications, excessive daytime sleepiness and obesity, while memory and attention impairment were obvious in phenotype Ⅱ. Phenotype Ⅲhad minimal complications, relatively better mental state with shorter time-course of snoring and apnea. Phenotype I differed significantly by higher severity, more severe hypoxemia, higher arousal index and longer WASO time（P<0.05）. Conclusion:the arousal index distribution varies among OSAHS patients with different age, and cluster analysis shows that patients with severe symptoms and more complications tend to have higher arousal index.

Relationship between serum brain-derived neurotrophic factor and cognitive impairment in children with sleep-disordered breathing.

Background: As an important neuroprotective factor, the brain-derived neurotrophic factor (BDNF) may have a key role in cognitive impairment in children with sleep-disordered breathing (SDB). The main aim of this study was to compare the levels of BDNF and tyrosine kinase receptor B (TrkB) in normal children and those with obstructive sleep apnea (OSA) and primary snoring (PS) and to explore a possible link between BDNF/TrkB, inflammation, and SDB with cognitive impairment in children. Methods: A total of 44 OSA children and 35 PS children who completed polysomnography between October 2017 and October 2019 were enrolled. At the same time, 40 healthy children during the same period were included as a control. Enzyme-linked immunosorbent assay was used to measure serum indices of BDNF, TrkB, interleukin-1beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α). Correlation and pooled analyses were performed between the cognitive scores and four serological indicators. Logistic regression was used to analyze the risk factors for cognitive impairment. Results: Significant differences were found in serum BDNF, TrkB, IL-1ß, and TNF-α between the three groups (all P < 0.01). The serum BDNF and TrkB in the OSA and PS groups were lower than those in the control group, whereas the serum IL-1ß and TNF-α were higher than those in the control group (all P < 0.05). Moreover, among these four indices, the strongest correlation was found between BDNF and the Chinese Wechsler Intelligence Scale (all P < 0.05). Logistic regression analysis revealed a correlation between OSA status, TrkB, and course of mouth breathing and cognitive status. Conclusion: The levels of serum BDNF and TrkB were related to cognitive impairment in children with SDB. Also, BDNF and TrkB could be used as noninvasive and objective candidate markers and predictive indices of cognitive impairment in children with SDB.

Professional satisfaction of health professional undergraduates and influencing factors in Hebei province, China.

BACKGROUND: Professional satisfaction of health professional students can impact on their medical professional achievement. Understanding the professional satisfaction of health professional students and identifying its relative factors is beneficial to strengthen the professionalism education of health professional students, and provide solid foundation for future medical achievements. METHODS: A self-made questionnaire was used to survey undergraduate students of six medical universities in Hebei province. The survey included three aspects: students' basic situation, professional selection and cognition, and basic situation of colleges. The Kruskal-Wallis H test was used to compare the professional satisfaction of students with different characteristics. All covariates were used in the ordinal logistics regression analysis to identify the independent factors associated with professional satisfaction. RESULTS: A total of 1238 (97.7%) students responded to the questionnaire in the survey, and 66.0% were women. Students with public health majors had decreased satisfaction compared with those with clinical-related majors. Professional satisfaction decreased among women compared with men. The non-first-choice students had lower professional satisfaction compared with the first-choice students. Students who chose their volunteer with the help of others had lower professional satisfaction compared with students who independently chose their volunteer. Students who did not understand the employment status had lower professional satisfaction compared with students who understood the employment status. Students with fewer employment prospects had lower professional satisfaction compared with students with bright employment prospects. Students generally dissatisfied with the canteen had lower professional satisfaction compared with students satisfied with the canteen. Students who were very satisfied or satisfied with teaching levels were more likely to have professional satisfaction. CONCLUSIONS: The professional satisfaction of health professional undergraduates in Hebei province is high. Employment-related aspects and university environment influence professional satisfaction including canteens, understanding of employment status, teachers' teaching level, etc., which are the main factors affecting professional satisfaction, but the factors such as student employment prospects and majors cannot be changed in the current environment.

Multi-Omics Association Reveals the Effects of Intestinal Microbiome-Host Interactions on Fat Deposition in Broilers.

Growing evidence indicates that gut microbiota factors cannot be viewed as independent in the occurrence of obesity. Because the gut microbiome is highly dimensional and complex, studies on interactions between gut microbiome and host in obesity are still rare. To explore the relationship of gut microbiome-host interactions with obesity, we performed multi-omics associations of gut metagenome, intestinal transcriptome, and host obesity phenotypes in divergently selected obese-lean broiler lines. Metagenomic shotgun sequencing generated a total of 450 gigabases of clean data from 80 intestinal segment contents of 20 broilers (10 of each line). The microbiome comparison showed that microbial diversity and composition in the duodenum, jejunum, ileum, and ceca were altered variously between the lean- and fat-line broilers. We identified two jejunal microbes (Escherichia coli and Candidatus Acetothermia bacterium) and four cecal microbes (Alistipes sp. CHKCI003, Ruminococcaceae bacterium CPB6, Clostridiales bacterium, and Anaeromassilibacillus sp. An200), which were significantly different between the two lines (FDR < 0.05). When comparing functional metagenome, the fat-line broilers had an intensive microbial metabolism in the duodenum and jejunum but degenerative microbial activities in the ileum and ceca. mRNA-sequencing identified a total of 1,667 differentially expressed genes (DEG) in the four intestinal compartments between the two lines (| log2FC| > 1.5 and FDR < 0.05). Multi-omics associations showed that the 14 microbial species with abundances that were significantly related with abdominal fat relevant traits (AFRT) also have significant correlations with 155 AFRT-correlated DEG (p < 0.05). These DEG were mainly involved in lipid metabolism, immune system, transport and catabolism, and cell growth-related pathways. The present study constructed a gut microbial gene catalog of the obese-lean broiler lines. Intestinal transcriptome and metagenome comparison between the two lines identified candidate DEG and differential microbes for obesity, respectively. Multi-omics associations suggest that abdominal fat deposition may be influenced by the interactions of specific gut microbiota abundance and the expression of host genes in the intestinal compartments in which the microbes reside. Our study explored the interactions between gut microbiome and host intestinal gene expression in lean and obese broilers, which may expand knowledge on the relationships between obesity and gut microbiome.

Highly efficient zinc finger peptide detection with ZIF-8-modified micropipets.

Zeolitic imidazolate framework-8 (ZIF-8)-modified micropipets can be an effective sensing platform for zinc finger peptides, the limit of detection of which reaches 10-2 µg ml-1. A series of techniques for detecting biomolecules are expected to emerge because of its simplicity, low cost, and universality by modifying other functional materials into the micropipets.

Influenza infection elicits an expansion of gut population of endogenous Bifidobacterium animalis which protects mice against infection.

BACKGROUND: Influenza is a severe respiratory illness that continually threatens global health. It has been widely known that gut microbiota modulates the host response to protect against influenza infection, but mechanistic details remain largely unknown. Here, we took advantage of the phenomenon of lethal dose 50 (LD50) and metagenomic sequencing analysis to identify specific anti-influenza gut microbes and analyze the underlying mechanism. RESULTS: Transferring fecal microbes from mice that survive virulent influenza H7N9 infection into antibiotic-treated mice confers resistance to infection. Some gut microbes exhibit differential features to lethal influenza infection depending on the infection outcome. Bifidobacterium pseudolongum and Bifidobacterium animalis levels are significantly elevated in surviving mice when compared to dead or mock-infected mice. Oral administration of B. animalis alone or the combination of both significantly reduces the severity of H7N9 infection in both antibiotic-treated and germ-free mice. Functional metagenomic analysis suggests that B. animalis mediates the anti-influenza effect via several specific metabolic molecules. In vivo tests confirm valine and coenzyme A produce an anti-influenza effect. CONCLUSIONS: These findings show that the severity of influenza infection is closely related to the heterogeneous responses of the gut microbiota. We demonstrate the anti-influenza effect of B. animalis, and also find that the gut population of endogenous B. animalis can expand to enhance host influenza resistance when lethal influenza infection occurs, representing a novel interaction between host and gut microbiota. Further, our data suggest the potential utility of Bifidobacterium in the prevention and as a prognostic predictor of influenza.

Multifunctional gold nanoparticle layers for controllable capture and release of proteins.

Protein modified functional surfaces have been applied extensively in the field of biomaterials and medicine. Regulation of the amount and activity of proteins on the material surface is always a challenge and a key research issue. A multifunctional micro/nano-composite based surface system for efficient controllable capture and release of proteins is proposed and studied in the present paper. This novel system contains (1) gold nanoparticles (AuNPs) co-modified with an enzyme and poly(methacrylic acid) (PMAA), e.g., AuNP-pyrophosphatase (PPase)-PMAA, as nanostructured protein carriers; (2) gold nanoparticle layers (GNPLs) modified with poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA), i.e., GNPL-PDMAEMA, as a micro/nano-structured support platform for surface bioactivity regulation. The capture-release of proteins and the regulation of surface bioactivity in this composite surface system were investigated under different conditions. The results showed that the proposed system is capable of protein capture and release with simple adjustment of the pH value from neutral pH to basic pH. When the pH of the system is stabilized at 7.0, the GNPL-PDMAEMA surface could adsorb plenty of AuNP-PPase-PMAA conjugates and maximum surface bioactivity occurred, but when the pH of the system is adjusted to 10.0, the GNPL-PDMAEMA surface could liberate almost all the AuNP-PPase-PMAA conjugates and thus surface bioactivity disappeared. Meanwhile, by cyclical variations between pH 7.0 and pH 10.0, this surface protein capture/release system could realize recycling and reuse of one certain protein multiple times, a series of proteins acting sequentially in accordance with pre-designed procedures, and a functional combination of multiple proteins. This recyclable multifunctional surface with the capability of protein capture/release has great potential in many applications, such as biomonitoring and biomolecule immobilization.

Deciphering the Role of Sulfonated Unit in Heparin-Mimicking Polymer to Promote Neural Differentiation of Embryonic Stem Cells.

Glycosaminoglycans (GAGs), especially heparin and heparan sulfate (HS), hold great potential for inducing the neural differentiation of embryonic stem cells (ESCs) and have brought new hope for the treatment of neurological diseases. However, the disadvantages of natural heparin/HS, such as difficulty in isolating them with a sufficient amount, highly heterogeneous structure, and the risk of immune responses, have limited their further therapeutic applications. Thus, there is a great demand for stable, controllable, and well-defined synthetic alternatives of heparin/HS with more effective biological functions. In this study, based upon a previously proposed unit-recombination strategy, several heparin-mimicking polymers were synthesized by integrating glucosamine-like 2-methacrylamido glucopyranose monomers (MAG) with three sulfonated units in different structural forms, and their effects on cell proliferation, the pluripotency, and the differentiation of ESCs were carefully studied. The results showed that all the copolymers had good cytocompatibility and displayed much better bioactivity in promoting the neural differentiation of ESCs as compared to natural heparin; copolymers with different sulfonated units exhibited different levels of promoting ability; among them, copolymer with 3-sulfopropyl acrylate (SPA) as a sulfonated unit was the most potent in promoting the neural differentiation of ESCs; the promoting effect is dependent on the molecular weight and concentration of P(MAG-co-SPA), with the highest levels occurring at the intermediate molecular weight and concentration. These results clearly demonstrated that the sulfonated unit in the copolymers played an important role in determining the promoting effect on ESCs' neural differentiation; SPA was identified as the most potent sulfonated unit for copolymer with the strongest promoting ability. The possible reason for sulfonated unit structure as a vital factor influencing the ability of the copolymers may be attributed to the difference in electrostatic and steric hindrance effect. The synthetic heparin-mimicking polymers obtained here can offer an effective alternative to heparin/HS and have great therapeutic potential for nervous system diseases.

Characterization of Vibrio cholerae isolates from 1976 to 2013 in Shandong Province, China

Abstract Cholera continues to be a serious public health issue in developing countries. We analyzed the epidemiological data of cholera from 1976 to 2013 in Shandong Province, an eastern coastal area of China. A total of 250 Vibrio cholerae isolates were selected for PCR analysis of virulence genes and pulsed-field gel electrophoresis (PFGE). The analysis of the virulence genes showed that the positive rates for tcpA and tcpI were the highest among strains from the southwest region, which had the highest incidence rate of cholera. Low positive rates for tcpA, tcpI and ctxAB among isolates from after 2000 may be an influencing factor contributing to the contemporary decline in cholera incidence rates. Spatiotemporal serotype shifts (Ogawa, Inaba, Ogawa, Inaba and O139) generally correlated with the variations in the PFGE patterns (PIV, PIIIc, PIa, PIIIb, PIIIa, PIb, and PII). O1 strains from different years or regions also had similar PFGE patterns, while O139 strains exclusively formed one cluster and differed from all other O1 strains. These data indicate that V. cholerae isolates in Shandong Province have continually undergone spatiotemporal changes. The serotype switching between Ogawa and Inaba originated from indigenous strains, while the emergence of serogroup O139 appeared to be unrelated to endemic V. cholerae O1 strains.

Characterization of Vibrio cholerae isolates from 1976 to 2013 in Shandong Province, China.

Cholera continues to be a serious public health issue in developing countries. We analyzed the epidemiological data of cholera from 1976 to 2013 in Shandong Province, an eastern coastal area of China. A total of 250 Vibrio cholerae isolates were selected for PCR analysis of virulence genes and pulsed-field gel electrophoresis (PFGE). The analysis of the virulence genes showed that the positive rates for tcpA and tcpI were the highest among strains from the southwest region, which had the highest incidence rate of cholera. Low positive rates for tcpA, tcpI and ctxAB among isolates from after 2000 may be an influencing factor contributing to the contemporary decline in cholera incidence rates. Spatiotemporal serotype shifts (Ogawa, Inaba, Ogawa, Inaba and O139) generally correlated with the variations in the PFGE patterns (PIV, PIIIc, PIa, PIIIb, PIIIa, PIb, and PII). O1 strains from different years or regions also had similar PFGE patterns, while O139 strains exclusively formed one cluster and differed from all other O1 strains. These data indicate that V. cholerae isolates in Shandong Province have continually undergone spatiotemporal changes. The serotype switching between Ogawa and Inaba originated from indigenous strains, while the emergence of serogroup O139 appeared to be unrelated to endemic V. cholerae O1 strains.