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ToxigenicIn this article, the mechanisms implying the probiotic effect againstAlthough many strains with ability against

Objective Goal of this work is to assess the feasibility to perform COVID-19 RNA tests within hospitals and communities experiencing SARS-CoV-2 virus outbreaks, to ultimately provide recommendations for hospitals with so-called fever clinics. In China, these specialised clinics within a hospital, specifically receive outpatients who have fever symptoms.Methods A team with expertise in the Exposure Analysis of Critical Control Points (EACCP) framework first identified potential infection routes during the testing for SARS-CoV-2, then constructed and tested flow diagrams, which were confirmed under actual conditions, demonstrating the feasibility to be carried out in hospitals with fever clinics. The team determined critical control points to mitigate the exposure risks at each control point.Findings The sampling and inactivation steps of clinical samples in fever clinics appeared to be associated with particularly high risk levels of exposure to SARS-CoV-2. Moderate levels of exposure were associated with storage and transportation of samples for inactivation; Low risk levels were associated with the transportation, storage and detection steps after inactivation.Conclusion To minimise risks of infection for personnel, optimised processes to carry out SARS-CoV-2 RNA tests in hospitals with fever clinics in China are proposed. The high risk of SARS-CoV-2 exposure during procedures preceding testing are the sampling and biological inactivation, which can be reduced by using full personal protective equipment and the use of BSL2 facilities in fever clinics or mobile BSL2 platforms. The implementation of the Exposure Analysis of Critical Control Points framework could facilitate rapid responses to outbreaks of emerging infectious diseases.

The previous target tracking algorithms based on correlation filters have excellent tracking performance. However, when encountering some challenging problems such as fast motion, occlusion, scale variations, motion blur, etc., tracking drift or even tracking failure occurs during the tracking process. Aiming at the above problems, we propose a novel tracking method. On the basis of kernelized correlation filter, a scale adaptive filter is added to adapt to the scale variations of the target during the tracking process. In addition, a feedback mechanism using the average peak-to-correlation energy (APCE) as the judgment criterion is introduced to enable the model to be updated under the premise of high-confidence and avoid tracking model corruption. Experimental results show that our algorithm performs better than traditional correlation filtering algorithms on challenging sequences.

Our current understanding of the host-microbiota interaction in the gut is dominated by studies focused primarily on prokaryotic bacterial communities. However, there is an underappreciated symbiotic eukaryotic protistic community that is an integral part of mammalian microbiota. How commensal protozoan bacteria might interact to form a stable microbial community remains poorly understood. Here, we describe a murine protistic commensal, phylogenetically assigned as Tritrichomonas musculis, whose colonization in the gut resulted in a reduction of gut bacterial abundance and diversity in wild-type C57BL/6 mice. Meanwhile, dietary nutrient and commensal bacteria also influenced the protozoan’s intestinal colonization and stability. While mice fed a normal chow diet had abundant T. musculis organisms, switching to a Western-type high-fat diet led to the diminishment of the protozoan from the gut. Supplementation of inulin as a dietary fiber to the high-fat diet partially restored the protozoan’s colonization. In addition, a cocktail of broad-spectrum antibiotics rendered permissive engraftment of T. musculis even under a high-fat, low-fiber diet. Furthermore, oral administration of Bifidobacterium spp. together with dietary supplementation of inulin in the high-fat diet impacted the protozoan’s intestinal engraftment in a bifidobacterial species-dependent manner. Overall, our study described an example of dietary-nutrient-dependent murine commensal protozoan-bacterium cross talk as an important modulator of the host intestinal microbiome. IMPORTANCE Like commensal bacteria, commensal protozoa are an integral part of the vertebrate intestinal microbiome. How protozoa integrate into a commensal bacterium-enriched ecosystem remains poorly studied. Here, using the murine commensal Tritrichomonas musculis as a proof of concept, we studied potential factors involved in shaping the intestinal protozoal-bacterial community. Understanding the rules by which microbes form a multispecies community is crucial to prevent or correct microbial community dysfunctions in order to promote the host’s health or to treat diseases.

The physiologic signals that regulate beige adipogenesis remain incompletely understood, especially those that limit browning and prevent overexpenditure of energy. In this study, the TNF family member cytokine lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT), also known as TNF super family protein 14 (TNFSF14), can inhibit adipose precursor differentiation into beige adipocytes. In acute cold stress, LIGHT deficiency in mice accelerated browning in the subcutaneous white adipose tissue (scWAT). Further experiments showed that LIGHT interacting with lymphotoxin-β receptor (LTβR) on adipose precursors blocked beige fat biogenesis. LTβR signals attenuated the JNK pathway, which contributed to their antibeiging effect. Blocking JNK activation using a small molecular inhibitor prevented cold-induced scWAT beiging. Furthermore, LIGHT/LTβR signals acted as an attenuator of white adipogenesis. LIGHT deficiency in mice promoted obesity during high-fat diet feeding. These findings identify the LIGHT axis as a regulator of adipose tissue homeostasis and suggest that LIGHT signaling functions as a mechanism to divert energy in favor of immune activation.-Kou, Y., Liu, Q., Liu, W., Sun, H., Liang, M., Kong, F., Zhang, B., Wei, Y., Liu, Z., Wang, Y. LIGHT/TNFSF14 signaling attenuates beige fat biogenesis.

The efficient capture of radioactive iodine (I-129, I-131) and radon (Rn-222) is crucial to the development of nuclear energy in spent fuel treatment. Herein, we successfully synthesized a new type of three-dimensional hydrolyzed collagen aerogel immobilized with catechin (Catechin@3DCF aerogel) as an effective adsorbent to remove iodine and radon through enzymatic hydrolysis, dialysis, freeze-drying, immobilization, and cross-linking. The as-prepared adsorbent was systematically characterized by FE-SEM, EDX, FT–IR, and XPS, showing that the adsorbent possesses ultra-high porosity, high content flake structure, and abundant adsorption sites on the surface of adsorbent. The results show that Catechin@3DCF aerogel exhibited excellent capture capacity for iodine and radon, with the maximum capture capacity of 222.67 wt% (88.5 wt% for 3DCF aerogel) and 44,877.9 Bq/Kg, respectively. Through the active group-shielding experiment analysis, the phenolic hydroxyl groups on the surface of adsorbent played a major role in iodine capture, followed by the -NHR group. In addition, mechanism studies have shown that the capture of iodine is mainly by chemical adsorption, while the capture of radon is mainly through physical adsorption, which is related to the numerous mesopores and flake structure of the adsorbent. Furthermore, Catechin@3DCF aerogel still maintains excellent adsorption capacity for iodine and radon under 60Co γ-ray irradiation at a total dose ranging from 10 to 350 kGy, indicating that it has excellent radiation resistance stability. Advantages such as novelty, ultra-high porosity, high-radiation stability, ultra-high capture capacity, environment-friendly, and low-cost indicate that biomass-derived Catechin@3DCF aerogel plays a role in the capture of radioactive iodine and radon from airborne effluents.

Bifidobacterium inhabiting the human and animal intestinal tract is known for its health-promoting effect. Tolerance to acid stress is crucial for bifidobacteria to survive and then exert their beneficial effects in the gut. A long-term adaptation in successive batch cultures was used as evolutionary engineering strategy to improve acid stress tolerance in an industrial probiotic strain, B. longum JDM301. Its derivative, JDM301AR showed higher resistance to several stress conditions, including acid stress than the parental strain, JDM301. To better understand bifidobacterial acid stress response, the changes of fatty acid (FA) in cell membrane of these two strains were determined. A shift in the production of FA in cell membrane, characterized by increased C14:0 was found, when JDM301AR was exposed to low-pH environment. It was implied that the increased production of C14:0 is associated with the acquisition of acid-tolerant phenotype for JDM301AR. High-throughput RNA-sequencing was performed to analyze the changes of gene expression profile after acid-exposure. The transcriptional profiles of JDM301AR and JDM301 under normal condition and acid stress were compared to reveal the different acid response between them. A total of 5 genes involved in FA metabolism were upregulated and no downregulated genes were found in response to acid stress in JDM301AR. The up-regulated BLJ_0565 and BLJ_1105 may play important roles in the modification of membrane FA composition of JDM301AR after acid exposure. Overall, these results suggested that successive batch cultures induced the acid stress tolerance of B. longum involved in transcriptional and physiological responses, including modification of cell wall and cell membrane, metabolism of amino acid and neutralization of internal pH by strengthening NH3 production and transport.

This study evaluated compliance with the comprehensive smoke-free law in public indoor places introduced in Shanghai in March 2017. Observations and PM2.5 monitoring over 30 min intervals in 8 types of the venue were conducted three times: within a month before implementation and 3- and 12-months post implementation. Observations of evidence of smoking decreased from 66.2% before legislation to 52.8% three months after (p = 0.002) and 49.7% one year after (p &lt, 0.001). The density of lit cigarettes also reduced significantly after implementation (p &lt, 0.001). When adjusting for outdoor, indoor PM2.5 levels were significantly lower after the legislation, but only by a small amount (three months later: &minus, 0.27, p = 0.08, one year later: &minus, 0.12, p = 0.03). Evidence of compliance was weakest in farmer&rsquo, s markets and bars, and smoking in male toilets did not change significantly. The reduction in smoking was affected by the management performance of their obligations. The comprehensive smoke-free law led to modest reductions in smoking and PM2.5 levels as a result, but from levels suggesting quite high levels of pre-compliance. However, compliance was limited in some areas, suggesting more effort is required on management to gain better compliance in some places like farmer&rsquo, s markets, bars, and toilets.

Objective: The aim of this study was to identify the potential psychological mechanism of well-being in migrants in Shanghai, China. Methods: A cross-sectional study was conducted in 2018. First, a literature review was conducted to understand the salutogenesis of migrants in China. Then, 2573 random participants were recruited from six workplaces and public places in six districts of Shanghai. The Chinese versions of the Patient Health Questionnaire-9 (PHQ-9), the Personal Wellbeing Index (PWI), and the Sense of Coherence (SOC) Scale were used to evaluate the depression, subjective well-being (SWB), and SOC of migrants. The t-test, ANOVA, and multiple linear regression and structural equation models (SEM) were used to analyze the correlations and paths among generalized resistant resources (GRRs), SOC, PHQ, and SWB. Results: The subjects were aged between 18 and 58 (mean, 28.17, SD, 6.99). SOC showed a positive correlation with SWB (r = 0.46, p &lt, 0.001) and a negative correlation to PHQ (r = &ndash, 0.53, p &lt, 0.001). After controlling for the demographic characteristics, we found that PHQ, SOC (comprehensibility, manageability, meaningfulness), and GRRs (income ratio, marital status) contributed 33.3% of the variance in SWB, and their linear regression coefficients were: &minus, 0.32 (p &lt, 0.001), 0.09 (p &lt, 0.001), 0.15 (p &lt, 0.001), 0.06 (p &lt, 0.05), and 0.16 (p &lt, 0.05), respectively. These findings not only confirmed the direct association among SOC, PHQ and SWB, but also verified two underlying mechanisms regarding the mediating effect of SOC by using SEM: (1) GRRs (income ratio, marital status) are positively associated with a higher SOC, which further contributes to favorable SWB, and (2) PHQ is negatively associated with poor SWB indirectly via SOC. Conclusion: Migrant workers with low SOC and high PHQ are vulnerable to poor well-being levels. Meanwhile, GRRs (income ratio, marital status) may strengthen the SOC level, and can be regarded as the basis of intervention. Further investigation may be needed to focus on external psychological support factors.

The conformation and stability of zein in solution are closely associated with its solvation process and influence the mechanical properties of the related zein-based materials. In this work, a common solvent dimethyl sulfoxide (DMSO) was used to dissolve zein, rather than solvents frequently used such as aqueous ethanol and acetic acid. It was found that DMSO could dissolve zein readily and the solution was stable for at least 2 weeks. Rheological analysis and small-angle X-ray scattering (SAXS) were employed to characterize the zein DMSO solution. Results of rheological analysis suggested a Huggins coefficient of 0.24, indicating DMSO to be a good solvent for zein. SAXS results revealed that zein adopted an elongated conformation and had dimensions of 2.8 nm × 2.8 nm × 14.8 nm in DMSO solution. Moreover, robust zein films were fabricated from zein DMSO solutions. The content of residual DMSO in the films was determined to be approximately 15 wt % by thermogravimetric analysis, in consistence with the value obtained by other two methods. The film showed a large breaking strain of 320.6% with a considerable breaking stress of 1.9 MPa, yielding a breaking energy of 376.2 MJ/m3. Therefore, the ease of dissolution and good mechanical performance of the final zein-based material make DMSO a potential solvent for fabrication of zein materials, thereby improving the scope of practical applications of zein.

The correlation filters are the core components of most trackers which achieve the excellent results both on accuracy and real-time. However, the previous trackers are prone to drift away from the target when dealing with the challenging situations, e.g. motion blur and fast motion, which leads to the performance of trackers degration. To solve the above problems, in this paper, we propose a novel algorithm which adds the re-detection mechanism to the traditional kernelized correlation filter for judging and verifying the reliability of the detected target before updating the model. We employ the average peak-to-correlation energy to evaluate the confidence level of the candidate position. The experiment results show that proposed algorithm is more accurate and successful than the traditional algorithms.

Injury to the biliary epithelium triggers cholangiopathies. However, factors involved in regulating the pathogenesis remains incompletely understood. Here, we report that the gut microbiota is important in regulating hepatobiliary fibroproliferative regenerative process. In helminth Clonorchis sinensis-induced bile duct injury model, wild-type mice showed more extensive peribiliary fibroproliferative responses than non-littermate IL-33-deficient mice. However, these reactions could be attenuated by co-housing of the animals together. In the meantime, the relatively fibroproliferative-resistant IL-33-deficient mice could become fibroproliferative-responsive especially in large intrahepatic bile duct by antibiotics treatment. Furthermore, microbiota-derived metabolite butyrate was able to inhibit biliary organoid expansion in vitro and temper 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced biliary fibrosis in vivo. Together, our data implies a potential way of management of hepatobiliary diseases by modulating gut microbiota.

Nano-scale zero-valent iron (NZVI) is easy to be agglomerated and passivated in the process of U(VI) reduction and fixation. Herein, a facile one-step process for titanium modified beaded segments like nano-zero-valent iron nanoparticles (FTNP) was designed and prepared for U(VI) adsorption-reduction from aqueous solution. The as-prepared NZVI, FTNP were characterized by Fourier transform infrared Spectroscopy (FT-IR), X-ray diffraction (XRD), X-Ray photoelectron spectra (XPS), Scanning electron microscope (SEM), Transmission electron microscope (TEM) and Energy dispersive X-ray spectrum (EDS). Results indicated that the beaded segments like FTNP were successful prepared. Furthermore, the uranium removal performance of FTNP with the effect of adsorption and reduction were investigated and showed excellent adsorption and reducibility for U(VI) from aqueous solution. Batch adsorption for U(VI) shown the U(VI) adsorption capacity of FTNP reached 734.4 mg g–1 (pH = 5.0). In the Fe-U reaction system, Fe2+ was generated as the primary reducing agent to reduce U(VI) from Fe0. Therefore, part of U(VI) was removed and reduced to U(IV), while others was precipitation hydrolyzed to schoepite, which also reduced to U(IV) and precipitated. This study may provide a novel and significant method for using nano-zero-valent iron to develop for wastewater decontamination.

In this study, the structural characterization of Sphallerocarpus gracilis polysaccharide (SGP) and its hypoglycaemic activities are reported for the first time. SGP, which has a weight average molar mass (Mw) of 7.413×105, was isolated from Sphallerocarpus gracilis and purified by ion-exchange chromatography. The polysaccharide is composed of rhamnose, arabinose, mannose, glucose and galactose, with the molar ratio of 4.12: 8.99: 5.45: 65.94: 15.50. The mechanism underlying the hypoglycaemic effect of SGP was evaluated. Experimental results showed that SGP protected pancreatic β-cells from alloxan damage by several possible mechanisms, including: (1) repairing free radical damage; (2) reducing the apoptosis of pancreatic β-cells by inhibiting the activities of caspase-3 and bax, and enhancing the activity of bcl-2; (3) stimulating insulin secretion and upregulating the pancreatic and duodenal homeobox 1 gene and the insulin gene and the pancreatic in pancreatic β-cells. The results obtained in this study suggest that SGP may be a promising therapeutic agent in the treatment of diabetes mellitus.

Toxin-antitoxin (TA) systems are widespread in bacteria and archaea. However, the roles of chromosomally encoded TA systems in bacterial physiology are still open to debate. In this study, a TA module-relBE in Bifidobacterium longum JDM301 (relBE(Bif)) was identified and its function in stress response was evaluated. Bioinformatics analysis of the whole genome sequences of JDM301 revealed a pair of linked genes encoding a RelBE-like TA system (RelBE(Bif)). Our results revealed a bicistronic operon formed by relBE(Bif) in JDM301. Over-expression of RelE(Bif) had a toxic effect on Escherichia coli, which could be neutralized by co-expression of its cognate antitoxin, RelB(Bif) Our data also demonstrated that RelE(Bif) is an mRNA interferase and that the activity of RelE(Bif) can be inhibited by RelB(Bif) These results suggest that RelE(Bif) is a toxic nuclease which arrests cell growth through mRNA degradation, and that the activity of RelE(Bif) can be abolished by co-expression of RelB(Bif) In addition, we also found that the expression of RelBE(Bif) is increased during osmotic stress, suggesting that RelBE(Bif) is activated under this adverse condition. Our results imply that the RelBE(Bif) TA module may represent a cell growth modulator which helps B. longum to deal with osmotic stress.

The pH-sensitive hydrogels composed of sodium caseinate (SC) and N,O-carboxymethyl chitosan (NOCC) were prepared and a new method to characterize the gelation process was presented in this work. Reological tests suggested that RSC/NOCC=3/7 (the weight ratio of SC and NOCC) was the best ratio of hydrogel. The well-developed three-dimensional network structures in the hydrogel were confirmed by AFM. Two structural parameters, tIS and tCS, denoted as the initial and critical structure formation time, respectively, were used to provide an exact determination of the start of structure formation and description of gelation process. The gelation process strongly depended on temperature changes, a high temperature resulted in an early start of gelation. The non-kinetic model suggested the higher activation energy in the higher temperatures was disadvantageous to structure formation, and vice versa. Due to the smart gel reported here was very stable at room temperature, we believed that the gel is required for applications in drug delivery or could be exploited in the development of potential application as molecular switches in the future.

Sphallerocarpus gracilis (S. gracilis) is a little-investigated edible plant and used as traditional Chinese medicine. In this study, polysaccharide extracted from S. gracilis,deproteined and purified. The polysaccharide (SGP) was chemically modified to obtain its sulfated derivatives (S-SGP) using the method of chlorosulfonic acid/pyridine (CSA/Pyr). In order to acquire the derivative with the highest degree of substitution (DS), the optimum conditions of the sulfation were obtained based on response surface design (RSD), and the structural characterizations and antioxidant properties of the S-SGP were comparatively investigated by Fourier transform infrared spectrometry (FT-IR), GC-MS analysis, size exclusion chromatography (SEC), and DPPH radical assay, hydroxyl radical assay, superoxide radical assay, and reducing power assay, respectively. Results showed that the modification was successful, and obtained the optimum combination of conditions. Compared with SGP, the sulfated polysaccharide with relatively the decreased degree of molecular weight (Mw) but the same composition of monosaccharides exhibited better antioxidant activities in DPPH, hydroxyl, superoxide radical and reducing power assay. These results indicated that the antioxidant activities in vitro of the S-SGP from S. gracilis may be related to combined effects of Mw, monosaccharide composition, and sulfate content.

Additional file 1. List of genes involved in NH3 production, peptidoglycan synthesis, pantothenate and CoA biosynthesis and cell division and chromosome partitioning expressed differently in JDM301AR compared with JDM301 in normal condition.

Current evidence to support extensive use of probiotics in inflammatory bowel disease is limited and factors that contribute to the inconsistent effectiveness of clinical probiotic therapy are not completely known. Here, we used Bifidobacterium longum JDM 301 as a model probiotic to study potential factors that may influence the effect of probiotics in experimental colitis. We found that the effect of B. longum JDM 301 in tempering experimental colitis varied across individual mice even with the same genetic background. The probiotic efficacy was highly correlated with the host gut microbial community features. Consumption of a diet rich in fat could exacerbate mucosal injury-induced colitis but could not change the host responsiveness to B. longum JDM 301 treatment, suggesting of potential mechanistic differences between regulating colitis pathogenesis, and modulating probiotic efficacies by the gut microbiota. Together, our results suggest that personalized microbiome features may modify the probiotic therapeutic effect and support the idea of personalized probiotic medicine in inflammatory bowel disease.

Edge detection and recognition is one of the most critical procedures in image processing and pattern recognition. Traditional Canny algorithm has some advantages, such as simple and fast execution times. It is not good enough when traditional Canny algorithm is applied in complex background images for objects edge detection. It is sensitive to noise and low location accuracy. To solve the shortcomings of traditional Canny algorithm, we propose an improved edge detection and recognition algorithm. The proposed edge detection algorithm can remove the influence of complex background images in the process of edge detection and characters segmentation. The effectiveness of the proposed algorithm is demonstrated by the experimental results. The proposed algorithm can eliminate the complex background of credit card and detect the meaningful edges of its numbers. The experimental results show the improved algorithm can obtain accurate edge position and good segmentation results.

Background Clostridium difficile (C. difficile) is a main cause of antibiotic-associated diarrhoea in humans. Several studies have been performed to reveal the prevalence rate of C. difficile in cats and dogs. However, little is known about the epidemiology of C. difficile in healthy pets in China. This study aimed to assess the burden of C. difficile shedding by healthy dogs and cats in China. Furthermore, the genetic diversity and antimicrobial susceptibility patterns of the recovered isolates were determined. Methods A total of 175 faecal samples were collected from 146 healthy dogs and 29 cats. C. difficile strains were isolated and identified from the feces of these pets. The characterized C. difficile strains were typed by multilocus sequence typing (MLST), and the MICs of the isolates were determined against ampicillin, clindamycin, tetracycline, moxifloxacin, chloramphenicol, cefoxitin, metronidazole and vancomycin by the agar dilution method. Results Overall, 3 faecal samples (1.7%) were C. difficile culture positive. One sample (0.7%) from a dog was C. difficile culture positive, while two cats (7.0%) yielded positive cultures. The prevalence rate differed significantly between cats and dogs. These isolates were typed into 3 MLST genotypes and were susceptible to chloramphenicol, tetracycline, metronidazole and moxifloxacin and resistant to ampicillin, clindamycin and cefoxitin. Notably, one strain, D141–1, which was resistant to three kinds of antibiotics and carried toxin genes, was recovered in the faeces of a healthy dog. Conclusion Our results suggest that common pets may be a source of pathogenic C. difficile, indicating that household transmission of C. difficile from pets to humans can not be excluded.

Current evidence to support extensive use of probiotics in inflammatory bowel disease is limited and factors contribute to the inconsistent effectiveness of clinical probiotic therapy are not completely known. Here, as a proof-of-concept, we utilized Bifidobacterium longum JDM 301, a widely used commercial probiotic strain in China, to study potential factors that may influence the beneficial effect of probiotics in experimental colitis. We found that the probiotic therapeutic effect was varied across individual mouse even with the same genetic background and consuming the same type of food. The different probiotic efficacy was highly correlated with different microbiome features in each mouse. Consumption of a diet rich in fat can change the host sensitivity to mucosal injury-induced colitis but did not change the host responsiveness to probiotic therapy. Finally, the host genetic factor TLR2 was required for a therapeutic effect of B. longum JDM 301. Together, our results suggest that personalized microbiome and genetic features may modify the probiotic therapeutic effect.

Probiotics might offer an attractive alternative to prevent and control Clostridium difficile (C. difficile) infection (CDI). Limited information is available on the ability of commercially used bifidobacterial strains to inhibit C. difficile. This study examined the anti-clostridial effects of Bifidobacterium longum JDM301, a widely used commercial probiotic strain in China, in vitro and in vivo. In vitro evaluation revealed a significant reduction in C. difficile counts when JDM301 was co-cultured with C. difficile, which was correlated with the significant decrease in clostridial toxin titres (TcdA and TcdB). Furthermore, the cell-free culture supernatants (CFS) of JDM301 inhibited C. difficile growth and degraded TcdA and TcdB. Notably, the results showed that acid pH promoted the degradation of TcdA by CFS from JDM301. Furthermore, comparative studies among 10 B. longum strains were performed, which showed that the inhibitory effect of CFS from JDM301 was similar with the other 8 B. longum strains and higher than strain BLY1. However, when it was neutralized, the significant different was lost. When present together, it was suggested that the acid pH induced by probiotics not only played important roles in the growth inhibition against C. difficile resulting in the reduction of toxins titres, but also directly promoted the degradation of clostridial toxin. In vivo studies proved that JDM301 partially relieved damage to tissues caused by C. difficile and also decreased the number of C. difficile and toxin levels. In summary, our results demonstrated that the commercial strain, JDM301 could be considered a probiotic able to exert anti-toxin capability and most of the CFS from Bifidobacterium were able to inhibit the growth of C. difficile, depending on acid pH. These results highlighted a potential that JDM301 could be helpful in preventing CDI and that most of the bifidobacterial strains could (at least partially) exert protective effects by reducing toxin titres through growth inhibition against toxigenic C. difficile.

To discover the potential functionalities of fenugreek gum (FG) in food applications and pharmaceutical industry, steady-shear flow, thixotropy and dynamical viscoelasticity tests were systemically carried out under a range of FG concentration (0.05–2.0%, w/v) and temperature (0–80 °C). The results showed that FG aqueous solutions exhibited Newtonian plateaus followed by shear-thinning regions which were found to be well correlated to the Carreau model. It was also found that the pseudoplastic behaviors of the FG aqueous solutions exhibited a concentration dependence. When the concentration of FG was above 1%, the system exhibited a gel-like behavior. Dynamical viscoelastic properties also showed a solid, elastic-like viscoelastic behavior. While solution with FG concentration of 0.05% exhibited a transition from a fluid-like to gel-like structure. The variation of the thixotropic index α as a function of FG concentration showed a stronger thixotropic behavior as the polymer concentration increased, which indicated a typical elastic behavior of FG solutions with high concentration. Multiwave temperature ramp test for 1.0% (w/v) FG aqueous solution showed that the solid-like behavior had a strong dependence on frequency rather than temperature, which was consistent with the results of oscillatory frequency sweep test. These results could provide a useful indicator for the applications of FG in food industry and other fields.

Probiotics might offer an attractive alternative to prevent and control Clostridium difficile (C. difficile) infection (CDI). Limited information is available on the ability of commercially used bifidobacterial strains to inhibit C. difficile. This study examined the anti-clostridial effects of Bifidobacterium longum JDM301, a widely used commercial probiotic strain in China, in vitro and in vivo. In vitro evaluation revealed a significant reduction in C. difficile counts when JDM301 was co-cultured with C. difficile, which was correlated with the significant decrease in clostridial toxin titres (TcdA and TcdB). Furthermore, the cell-free culture supernatants (CFS) of JDM301 inhibited C. difficile growth and degraded TcdA and TcdB. Notably, the results showed that acid pH promoted the degradation of TcdA by CFS from JDM301. Furthermore, comparative studies among 10 B. longum strains were performed, which showed that the inhibitory effect of CFS from JDM301 was similar with the other 8 B. longum strains and higher than strain BLY1. However, when it was neutralized, the significant different was lost. When present together, it was suggested that the acid pH induced by probiotics not only played important roles in the growth inhibition against C. difficile resulting in the reduction of toxins titres, but also directly promoted the degradation of clostridial toxin. In vivo studies proved that JDM301 partially relieved damage to tissues caused by C. difficile and also decreased the number of C. difficile and toxin levels. In summary, our results demonstrated that the commercial strain, JDM301 could be considered a probiotic able to exert anti-toxin capability and most of the CFS from Bifidobacterium were able to inhibit the growth of C. difficile, depending on acid pH. These results highlighted a potential that JDM301 could be helpful in preventing CDI and that most of the bifidobacterial strains could (at least partially) exert protective effects by reducing toxin titres through growth inhibition against toxigenic C. difficile.

Bifidobacterium longum strain JDM301, a widely used commercial strain in China, encodes at least two MazEF-like modules and one RelBE-like toxin-antitoxin (TA) system in its chromosome, designated MazE 1 F 1 Bif , MazE 2 F 2 Bif , and RelBE Bif , respectively. Bacterial TA systems play an important role in several stress responses, but the relationship between these TA systems is largely unknown. In this study, the interactions between MazF 1 Bif and MazE 2 Bif or RelB Bif were assessed in B. longum strain JDM301. MazF 1 Bif caused the degradation of tufA Bif mRNA, and its toxicity was inhibited by forming a protein complex with its cognate antitoxin, MazE 1 Bif . Notably, MazF 1 Bif toxicity was also partially neutralized when jointly expressed with noncognate antitoxin MazE 2 Bif or RelB Bif . Our results show that the two noncognate antitoxins also inhibited mRNA degradation caused by MazF 1 Bif toxin. Furthermore, the physical interplay between MazF 1 Bif and its noncognate antitoxins was confirmed by immunoprecipitation. These results suggest that MazF 1 Bif can arrest cell growth and that MazF 1 Bif toxicity can be neutralized by its cognate and noncognate antitoxins. These results imply that JDM301 uses a sophisticated toxin-antitoxin interaction network to alter its physiology when coping with environmental stress. IMPORTANCE Although toxin-antitoxin (TA) systems play an important role in several stress responses, the regulatory mechanisms of multiple TA system homologs in the bacterial genome remain largely unclear. In this study, the relationships between MazE 1 F 1 Bif and the other two TA systems of Bifidobacterium longum strain JDM301 were explored, and the interactions between MazF 1 Bif and MazE 2 Bif or RelB Bif were characterized. In addition, the mRNA degradation activity of MazF 1 Bif was demonstrated. In particular, the interaction of the toxin with noncognate antitoxins was shown, even between different TA families (MazF 1 Bif toxin and RelB Bif antitoxin) in JDM301. This work provides insight into the regulatory mechanisms of TA systems implicated in the stress responses of bifidobacteria.

Core-shell structured multifunctional nanocarriers (NCs) of ZnO quantum dots-conjugated gold nanoparticles (Au NPs) as core and amphiphilic hyperbranched block copolymer as shell were synthesized for targeted anticancer drug delivery. The amphiphilic hyperbranched block copolymer contained poly(l-lactide) (PLA) inner arm and folate (FA)-conjugated a sulfated polysaccharide from Gynostemma pentaphyllum Makino (GPPS-FA) outer arm. The structure and properties of core-shell structured multifunctional nanocarriers were characterized and determined by UV-visible spectra, FT-IR spectra, X-ray diffraction (XRD), fluorescence spectroscopy and TEM analyses. The release results indicated that camptothecin (CPT) release from NCs at pH 7.4 was much greater than that at pH 5.3. The cytotoxicity studies showed that both the blank NCs and the CPT-loaded NCs provided high anticancer activity against Hela cells. Furthermore, nanocarriers gained specificity to target model cancer cells in this study due to the enhanced cell uptake mediated by FA moiety. The results indicated that the NCs not only had great potential as tumor-targeted drug delivery nanocarrier, but also had an assistant role in the treatment of cancer.

For centuries, Patrinia heterophylla had been used in China to treat many diseases including tumor. Triterpenes has been identified as the major active constituents in Patrinia heterophylla. To elucidate the antitumor mechanism of triterpenes from Patrinia heterophylla1 (TPH), a proteomic analysis is carried out with TPH treatment in K562 cells. The total proteins extracted from TPH treated K562 cells are analyzed by two dimensional gel electrophoresis (2-DE) and compared with those untreated K562 cells. Mass spectrometry is applied to identify the differentially expressed proteins. Twenty-three differentially expressed significant proteins are discovered. Eight proteins are later identified by mass spectrometry (MALDI-TOF-MS) and Mascot software. Among them, four proteins are up-regulated (Aldolase A, Glyceraldehyde-3-phosphate dehydrogenase, Flavin reductase and Hemoglobin subunit) and four proteins were down-regulated (Heat-shock protein 90 〈Alpha〉 (HSP90-〈Alpha〉), Eukaryotic translation initiation factor 5A, Moesin, tublin) by TPH treatment in K562 cells. The identified proteins are associated with energy metabolism, oxidative stress, apoptosis, signal transduction, differential induction, and protein biosynthesis. These findings might provide valuable insights into the antitumor mechanism of TPH in K562 cells.

The heterotrimeric G protein subunit Gsα couples receptors to activate adenylyl cyclase and is required for the intracellular cAMP response and protein kinase A (PKA) activation. Gsα is ubiquitously expressed in many cell types; however, the role of Gsα in neural crest cells (NCCs) remains unclear. Here we report that NCCs-specific Gsα knockout mice die within hours after birth and exhibit dramatic craniofacial malformations, including hypoplastic maxilla and mandible, cleft palate and craniofacial skeleton defects. Histological and anatomical analysis reveal that the cleft palate in Gsα knockout mice is a secondary defect resulting from craniofacial skeleton deficiencies. In Gsα knockout mice, the morphologies of NCCs-derived cranial nerves are normal, but the development of dorsal root and sympathetic ganglia are impaired. Furthermore, loss of Gsα in NCCs does not affect cranial NCCs migration or cell proliferation, but significantly accelerate osteochondrogenic differentiation. Taken together, our study suggests that Gsα is required for neural crest cells-derived craniofacial development.

Toxin-antitoxin (TA) systems are widespread in bacteria and archaea. However, the roles of chromosomally encoded TA systems in bacterial physiology are still open to debate. In this study, a TA module-relBE in Bifidobacterium longum JDM301 (relBE(Bif)) was identified and its function in stress response was evaluated. Bioinformatics analysis of the whole genome sequences of JDM301 revealed a pair of linked genes encoding a RelBE-like TA system (RelBE(Bif)). Our results revealed a bicistronic operon formed by relBE(Bif) in JDM301. Over-expression of RelE(Bif) had a toxic effect on Escherichia coli, which could be neutralized by co-expression of its cognate antitoxin, RelB(Bif) Our data also demonstrated that RelE(Bif) is an mRNA interferase and that the activity of RelE(Bif) can be inhibited by RelB(Bif) These results suggest that RelE(Bif) is a toxic nuclease which arrests cell growth through mRNA degradation, and that the activity of RelE(Bif) can be abolished by co-expression of RelB(Bif) In addition, we also found that the expression of RelBE(Bif) is increased during osmotic stress, suggesting that RelBE(Bif) is activated under this adverse condition. Our results imply that the RelBE(Bif) TA module may represent a cell growth modulator which helps B. longum to deal with osmotic stress.

Asymmetric cell division, which plays fundamental roles in generating cell diversity during development, requires elaborate interactions between extrinsic cues and intrinsic cues. However, the precise nature of this type of interaction and its involving signaling mechanisms are poorly understood. Here, we demonstrate that Gαs is present in the proliferative region of ventricular zone in mouse developing neocortex and co-localizes with intrinsic cell fate determinant protein Numb in dividing apical progenitors. Targeted ablation of Gαs subunit in the cortical progenitor causes an alteration from asymmetric to symmetric cell division, consequently leading to increased progenitor proliferation. Mechanistically, we show that Gαs deletion significantly reduces Numb expression and activates notch signaling. Therefore, these results reveal a novel role of Gαs in control of neural progenitor asymmetric cell division via suppressing Numb mediated Notch signaling inhibition.

A series of eight novel podophyllotoxin derivatives were designed, synthesized and evaluated for biological activities. The antiproliferative activities were tested against a panel of human cancer cell lines (K562, SGC, Hela and HepG) and the inhibition of tubulin polymerization was also evaluated. Compound 8e displayed significant antiproliferative activities for all four cell lines and strong levels of tubulin polymerization inhibition effect. Combined with cell apoptosis and cell cycle analysis, it demonstrated that compound 3e that effectively interfere with tubulin dynamics prevent mitosis in cancer cells, leading to cell cycle arrest and, eventually dose dependent apoptosis. All experimental measurements were also supported by molecular docking simulations of colchicine binding site, which revealed the governing forces for the binding behavior and a good relationship with anti-tubulin activity and antiproliferative activities. The synthesis and biological studies provided an interesting new class of antitubulin agents for development of lead compounds and also a direction for further structure modification to obtain more potent anti-cancer drugs.

Sulfated modification of a polysaccharide obtained from Radix hedysari (RHP) was studied. Four sulfated derivatives (RHPS) with variable degrees of substitution (DS) were obtained by the chlorosulfonic acid method with ionic liquids (ILs) as solvent and 4-dimethylaminopyridine (DMAP) as catalyst. The structures of RHPS were characterized by FT-IR spectra and ¹³C NMR spectra, and the results indicated that the sulfated groups were modified mainly at the C-6 position and C-2 position. Four kinds of RHPS showed different DS ranging from 0.63 to 1.45, and different weight-average molecular mass (Mw) ranging from 60.8 to 71.1 kDa with a little degradation. Compared with RHP, all of RHPS exhibited obvious antitumor activity on A549 cells and BGC-823 cells in vitro. However, they had no obvious influence on HEK293 cells, which indicated that they had low toxicity to normal cells. Flow cytometric studies indicated that the treatment of RHPS against A549 cells and BGC-823 cells could mediate the cell-cycle arrest in the G1 phase.

Phosphorylated modification of a polysaccharide obtained from Radix Hedysari (RHP) was studied. Three phosphorylated polysaccharides (RHPP) with variable degrees of substitution (DS(p)) were obtained with 4-dimethylaminopyridine (DMAP) and N, N' Dicyclocarbodiimide (DCC) as catalyst. The structures of RHPP were characterized by FT-IR spectra and (13)C NMR spectra. Depending on different reaction time, RHPP showed different DS(p) ranging from 0.30 to 0.66, and different Mw ranging from 86.6 to 89.7 KDa. Compared with RHP, RHPP exhibited superior antioxidant activities in vitro, which indicated that phosphorylated modification could enhance antioxidant activities of RHP. Furthermore, it was obvious that the DS(p) had a significant effect on the antioxidant activity.

The traditional experiment teaching system of mechanical major has a lot of shortages, such as fewer class hours and fewer experiment types. Therefore, it has become a key point in the reformation of education at present. The reformational target is to construct a comprehensive experiment platform of mechanical major as the main part of experiment teaching, to promote updating the experiment content through creation of experiment, to build experiment teaching system of “three platforms, three levels, modularization and open type”. Laboratory facilities are innovated by means of students’ directing or participating in scientific research items and introduction of advanced technology. The comprehensive experiment platform has benefited to a large number of students of some majors including mechanical manufacture and automation, vehicle engineering, electric work and automation, industrial automation. Some teaching achievement awards are obtained. Scientific research atmosphere of students is animated.