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ABSTRACT: Oxidative stress is a crucial factor in the age-related decline in physiological, genomic, metabolic, and immunological functions. We screened Lactiplantibacillus plantarum JS19, which has been shown to possess therapeutic properties in mice with ulcerative colitis. In this study, L. plantarum JS19 used as the adjunct starter culture in fermented goat milk (LAF) was employed to alleviate d-galactose-induced aging and regulate intestinal flora in an aging mouse model. The oral administration of LAF effectively improved the health of spleen and kidney in mice, while mitigating the hepatocyte and oxidative damage induced by d-galactose. Additionally, LAF alleviated d-galactose-induced dysbiosis of the intestinal flora by reducing the abundance of harmful bacteria Desulfovibrio and Helicobacter, while greatly promoting the growth of beneficial Rikenellaceae_RC9_gut_group and Eubacterium. Biomarker 5-hydroxyindole-3-acetic acid was found to be positively linked with those harmful bacteria, whereas bio-active metabolites were strongly correlated with the beneficial genus. These observations suggest that LAF possesses the capability to mitigate the effects of d-galactose-induced aging in a mouse model through the regulation of oxidative stress, the gut microbiota composition, and levels of fecal metabolites. Consequently, these findings shed light on the potential of LAF as a functional food with antiaging properties.

Abstract Background Lung cancer (LC) is one of the most devastating diseases worldwide, there is growing studies confirm the role of impaired lung function in LC susceptibility. Moreover, gut microbiota dysbiosis is associated with LC severity. Whether alterations in gut microbiota and metabolites are associated with long-term lung dysfunction in LC patients remain unclear. Our study aimed to analyze the risk factors in LC patients with impaired pulmonary function based on the characteristics of the gut microbiome and metabolites. Methods Fecal samples from 55 LC patients and 28 benign pulmonary nodules patients were collected. Pulmonary ventilation function was graded according to the American Thoracic Society/ European Respiratory Society (ATS/ERS) method. LC patients were divided into 3 groups, including 20 patients with normal lung ventilation, 23 patients with mild pulmonary ventilation dysfunction and 12 patients with moderate or above pulmonary ventilation dysfunction. The fecal samples were analyzed using 16 S rRNA gene amplicon sequencing and metabolomics. Results The gut microbiome composition between LC patients and benign pulmonary nodules patients presented clearly differences based on Partial Least Squares Discriminant Analysis (PLS-DA). Pulmonary ventilation function was positively correlated with LC tumor stage, the richness and diversity of the gut microbiota in LC patients with moderate or above pulmonary ventilation dysfunction increased significantly, characterized by increased abundance of Subdoligranulum and Romboutsia. The metabolomics analysis revealed 69 differential metabolites, which were mainly enriched in beta-Alanine metabolism, styrene degradation and pyrimidine metabolism pathway. The area under the curve (AUC) combining the gut microbiome and metabolites was 90% (95% CI: 79-100%), indicating that the two species and four metabolites might regarded as biomarkers to assess the prediction of LC patients with impaired pulmonary function. Conclusions Our results showed that microbiome and metabolomics analyses provide important candidate to be used as clinically diagnostic biomarkers and therapeutic targets related to lung cancer with impaired pulmonary function.

Abstract Background Psoriasis is an inflammatory disease mediated by helper T (Th)17 and Th1 cells. MicroRNA-125a (miR-125a) is reduced in the lesional skin of psoriatic patients. However, the mechanism by which miR-125a participates in psoriasis remains unclear. Methods The levels of miR-125a-5p and its downstream targets (ETS-1, IFN-γ, and STAT3) were detected in CD4+ T cells of healthy controls and psoriatic patients by quantitative real-time PCR (qRT-PCR). In vitro, transfection of miR-125a-5p mimics was used to analyze the effect of miR-125a-5p on the differentiation of Th17 cells by flow cytometry. Imiquimod (IMQ)-induced mouse model was used to evaluate the role of upregulating miR-125a-5p by intradermal injection of agomir-125a-5p in vivo. Results miR-125a-5p was downregulated in peripheral blood CD4+ T cells of psoriatic patients, which was positively associated with the proportion of regulatory T cells (Tregs) and negatively correlated with the Psoriasis Area and Severity Index (PASI) score. Moreover, the miR-125a-5p mimics promoted the differentiation of Tregs and downregulated the messenger RNA (mRNA) levels of ETS-1, IFN-γ, and STAT3 in murine CD4+ T cells. Furthermore, agomir-125a-5p alleviated psoriasis-like inflammation in an IMQ-induced mouse model by downregulating the proportion of Th17 cells. Conclusions miR-125a-5p may have therapeutic potential in psoriasis by restoring the suppressive function of Tregs on Th17 cells through targeting STAT3, and on Th1 cells indirectly through targeting ETS-1 and IFN-γ.

ABSTRACT: This study aimed to evaluate the effects of added jujube polysaccharide (JP) and Lycium barbarum polysaccharide (LBP) on the texture, rheological properties, and microstructure of goat milk cheese. Seven groups of fresh goat milk cheese were produced with 4 levels (0, 0.2, 0.6, and 1%, wt/wt) of JP and LBP. The goat milk cheese containing 1% JP showed the highest water-holding capacity, hardness, and the strongest rheological properties by creating a denser and more stable casein network structure. In addition, the yield of goat milk cheese was substantially improved as a result of JP incorporation. Cheeses containing LBP expressed lower fat content, higher moisture, and softer texture compared with the control cheese. Fourier-transform infrared spectroscopy and low-field nuclear magnetic resonance analysis demonstrated that the addition of JP improved the stability of the secondary protein structure in cheese and significantly enhanced the binding capacity of the casein matrix to water molecules due to strengthened intermolecular interactions. The current research demonstrated the potential feasibility of modifying the texture of goat milk cheese by JP or LBP, available for developing tunable goat milk cheese to satisfy consumer preferences and production needs.

Objective: Study on the non-alkaloid chemical constituents with novel structure and their biological activities from the w-butanol fraction of the leaves of Rauvolfia vomitoria. Methods: The w-butanol fraction of R. vomitoria was separated by silica gel, ODS, and Sephadex LH-20 chromatography column, as well as semi-preparative HPLC to obtain five compounds. Their structures were identified by extensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR, and ECD analysis. All the isolated compounds were evaluated their AChE inhibitory activities by Ellman’s method with slight modification, their vasorelaxant activities against phenylephrine-induced contraction of rat mesenteric arteries, and their inhibitory activity of a-glucosidase employing pNPG as substrate. Results: Two new phenylpropanoids (1-2) along with three known compounds, methyl trans-3,4,5-trimethoxycinnamate (3), methyl cis-3,4,5-trimethoxycinnamate (4), and 3,4,5-trimethoxybenzoic acid methyl ester (5), were isolated from the leaves of R.vomitoria. The five isolated compounds did not show significant tested activity. Conclusion: Chemical investigation of the leaves of R. vomitoria led to the isolation and identification of two new phenylpropanoids (1–2), expanding the study of non-alkaloids in the genus of Rauvolfia and enriching the chemical diversity of this genus.

ABSTRACT: Antibiotic resistance genes, as newly emerging contaminants, have become a serious challenge to public health through the food chain. The gut of humans and animals is an important reservoir for the development and dissemination of antibiotic resistance genes because of the great abundance and diversity of intestinal microbiota. In the present study, we evaluated the influence of goat milk on the diversity and abundance of antibiotic resistance genes and gut microbial communities, especially pathogenic bacteria. Male mice were used, 12 for each of the 2 groups: a control group that received sterile distilled water and a treated group that received goat milk, and gut microbiota and antibiotic resistance genes were compared in these groups using metagenomic analysis. The results revealed that ingestion of goat milk decreased the diversity and abundance of antibiotic resistance genes in the mice gut. The relative abundance of fluoroquinolone, peptide, macrolide, and β-lactam resistance genes in the total microbial genes significantly decreased after the intervention. Goat milk intake also significantly reduced the abundance of pathogenic bacteria, such as Clostridium bolteae, Clostridium symbiosum, Helicobacter cinaedi, and Helicobacter bilis. Therefore, goat milk intake might decrease the transfer potential of antibiotic resistance gene to pathogenic bacteria in the gut. In addition, bacteria with multiple resistance mechanisms accounted for approximately 4.5% of total microbial communities in the control group, whereas it was not detectable in the goat milk group, indicating the total inhibition by goat milk intake. This study highlights the influence of goat milk on antibiotic resistome and microbial communities in the gut, and provides a new insight into the function of goat milk for further study.

ABSTRACT: Aflatoxin M1 (AFM1) is a common toxin in dairy products that causes acute and chronic human health disorders. Thus, the development of a rapid and accurate AFM1 detection method is of vital importance for food safety monitoring. This work was to develop a novel electrochemical aptasensor for sensitive and specific determination of AFM1. The dendritic-like nanostructure was formed on the gold electrode surface by layer-by-layer assembly of gold-silver core-shell nanoparticles modified with DNA conjugates. In the presence of AFM1, the specific recognition between AFM1 and Apt caused the disassociation of the DNA controlled dual Au@Ag conjugates from the surface of the electrode, causing less methylene blue to bind to the surface and weakening the electrochemical signal. The more AFM1 there is, the weaker the electrochemical signal. Transmission electron microscope results showed that the successfully synthesized Au@Ag nanoparticles exhibited a core-shell structure with Au as core and Ag as shell, and their average diameter was about 30 nm. Under optimal conditions, the electrochemical aptasensor showed a wide detection ranging from 0.05 ng mL−1 to 200 ng mL−1, and a low detection limit of 0.02 ng mL−1. Moreover, the proposed strategy has been successfully applied to the detection of AFM1 in cow, goat, and sheep milk samples with satisfactory recoveries ranging from 91.10% to 104.05%. This work can provide a novel rapid detection method for AFM1, and also provide a new sensing platform for the detection of other toxins.

IntroductionGoat milk is an attractive food due to its high nutritional values, easy digestibility and hypoallergenicity, but has an undesirable “goaty” flavor.MethodsIn this study, goat yogurt was fermented with four probiotics, respectively, including Lactobacillus acidophilus (GYA), Bifidobacterium animalis (GYB), Lactobacillus casei (GYC) and Lactobacillus plantarum (GYP), and tested for texture, organoleptic, and biological properties during a 4-week storage period at the refrigerated temperature.ResultsAll goat yogurt with probiotics showed an increase on titratable acidity and a corresponding downward trend on pH value. Viable counts of L. acidophilus and L. casei were above 6 log cfu/mL at the end of the storage, which met the minimum standards for viable probiotic bacteria in yogurt specified by the Food and Agriculture Organization of United Nation (FAO). The texture and organoleptic characteristics of fermented goat milk depended on the strain and the storage period. DPPH free radical scavenging rate and ferric reducing antioxidant power activity gradually increased in all goat yogurts during the storage and yogurt with probiotic bacteria showed higher values than those of GY0.DiscussionAmong all probiotic containing goat yogurts, GYC exhibited the desirable characteristics of hardness, adhesiveness, water holding capacity, antioxidant activity during the whole storage. Furthermore, the addition of L. casei effectively weakened the goaty flavor and enhanced the overall acceptability. Thus, fermented goat milk with L. casei is optional for the development of goat milk product with satisfactory texture properties, pleasant sensory quality and high bioactivity.

In this study, we compared the content of main components in goat colostrum and mature milk, and evaluated their influences on the intestinal microbiota to establish the correlations between milk components and functional features of the intestinal microbiota. Compared with goat mature milk, colostrum had significantly higher contents of protein, fat, minerals, dry matter, EGF, IGF-I, LTF and IgG, but lower concentrations of lactose and cAMP. The metagenomic analysis indicated that ingestion of mature milk increased the abundance of probiotic bacteria Lactobacillus and Muribaculum, while goat colostrum intake could promote the growth of probiotics Lactobacillus and Alistipes, but also the pathogen Helicobacter. Fat content was positively associated with the abundance of Helicobacter. Our study provided evidence that goat colostrum and mature milk could change the composition and structure of the intestinal microbiota community in different ways, which might drive the downstream effects on the host’s metabolism and health.

Cooperative vehicle safety system (CVSS) rely on periodical beacons to track neighboring vehicles.High traffic density often causes channel congestion,seriously damaging the performance of CVSS.Existing congestion control strategies aim to ensure the performance in network layer,without considering the service requirements of vehicles in different driving contexts.To solve the problem,a distributed congestion control strategy using network utility maximization (NUM) theory was proposed.First of all,the NUM model for channel resource allocation was introduced.A utility function reflecting vehicle’s safety requirements was proposed in the model.Then under the condition of fixed transmit powers,a optimization problem of channel resource allocation was proposed.Lastly,to solve the optimization problem,a distributed congestion control algorithm named utility-based rate congestion control (UBRCC) algorithm was designed,the algorithm worked out the optimal beaconing rate by updating vehicle’s congestion price,realizing the resource allocation according to vehicle’s safety requirements.Simulation results validate that UBRCC algorithm can efficiently control channel congestion,reduce transmission delay,ensure reliable data transmission and satisfies the requirements of safety applications.

Based on the computer simulation technology of zero memory nonlinearity (ZMNL), this paper combines with the backscattering features of sea clutter and conducts simulation for four typical backscattering coefficient empirical models of sea clutter, namely, Technology Service Corporation, Georgia Institutes of Technology, Hybrid Sea Clutter Model, and Naval Research Laboratory. According to the results, the signals of sea clutter simulated by zero memory nonlinearity are able to well satisfy the requirements of spectrum characteristics and amplitude distribution according to experiments on the fitting characteristics of simulated signals. After that, the above-mentioned sea clutter scattering coefficient fitting characteristics are applied to the finite difference time domain (FDTD) electromagnetic scattering equation of the numerical method, and the optimal recursive solution to the backward scattering area fitted by the above four semi-empirical models is proposed for the first time. Then, the method of discretizing the power spectrum equation of the differential form is combined with the FDTD discrete form. The numerical results of discrete simulation take the form of the random phase ω between 0 and 2π and then are converted into a basic iteration of one-dimensional rough length, thus realizing time domain power spectrum inversion. Finally, combined with the above conclusions, this paper proposes a new statistical model based on sea surface backscatter coefficient to invert the two-dimensional sea surface, that is, the three-parameter statistical model. At the same time, this paper further deduces the backscattering function of sea clutter based on random distribution and points out that the incident frequency and the rubbing angle are the main factors affecting the sea clutter scattering model. Based on this conclusion, this paper combines the sea clutter estimation model and the directional function model to simulate a two-dimensional random rough sea surface satisfying the physical laws of the ocean.

Combining the contrast characteristics of Wen's directional spectrum and Donelan's distribution function, this paper proposed a simulation model of 2-D random rough sea surface based on improved Wen's spectrum and Monte Carlo method, and analyzes distribution characteristics of the 2-D random rough sea surface under the condition of 320° wind direction, different wind speeds, and fetch. On the basis of the classical two-scale method for calculating the electromagnetic scattering of the sea surface, this paper attempts to compare the electromagnetic scattering results of the above simulated 2-D random rough sea surface with the backscattering simulation data of four typical semi-empirical sea clutter models, such as Technology Service Corporation, the Georgia Institutes of Technology, the Hybrid Sea Clutter Model, and the Naval Research Laboratory for the first time. Then, the electromagnetic scattering characteristics of 2-D random rough sea surface with improved Wen's spectrum in HH and VV polarization modes under different sea conditions, grazing angle, and incident frequency are studied. Finally, this paper analyzes the fitting characteristics between the above model and improved Wen's spectrum from the perspective of inversion of the wave spectrum by combining the spectral characteristics of the simulated wave spectrum and summarizes the respective adaptive ranges of different models.

Study region: Tarago Reservoir, Victoria, Australia. Study focus: This study investigates the influence of rainfall, river inflow and wind on the temperature stratification of the Tarago Reservoir by incorporating atmospheric and bathymetric conditions using a three-dimensional hydrodynamic model. New hydrological insights for this region: In this study, a three-dimensional (3D) hydrodynamic model was developed and applied to the Tarago Reservoir. The model allowed 3D visualization of the thermal structure, and the seasonal and longitudinal differences in stratification could be quantified using the Schmidt stability index. The simulation results revealed longitudinal differences in thermal structure among the riverine, transition, and lacustrine zones. The bathymetry affects the lake stratification and stability; furthermore, the strong vertical current caused by the sharp bathymetry gradient significantly weakens the stability in deep zones. In addition, this study assessed the impacts of rainfall and wind on lake stability using sensitivity analysis. The results indicated that rainfall decreases the water temperature of the lake but hardly affects the summer stratification. Moreover, the wind not only influences the intensity and duration of stratification but also contributes to the heat storage of waterbodies. The patterns of water current velocities and temperature also showed that the circulation generated by overflow and underflow plumes have a crucial effect on the thermal structure of the transition and lacustrine zones.

As sessile organisms, plants face a variety of environmental challenges. Their reproduction and survival depend on their ability to adapt to these stressors, which include water, heat stress, high salinity, and pathogen infection. Failure to adapt to these stressors results in programmed cell death and decreased viability, as well as reduced productivity in the case of crop plants. The growth and development of plants are maintained by meiosis and mitosis as well as endoreduplication, during which DNA replicates without cytokinesis, leading to polyploidy. As in other eukaryotes, the cell cycle in plants consists of four stages (G1, S, G2, and M) with two major check points, namely, the G1/S check point and G2/M check point, that ensure normal cell division. Progression through these checkpoints involves the activity of cyclin-dependent kinases and their regulatory subunits known as cyclins. In order for plants to survive, cell cycle control must be balanced with adaption to dynamic environmental conditions. In this review, we summarize recent advances in our understanding of cell cycle regulation in plants, with a focus on the molecular interactions of cell cycle machinery in the context of stress tolerance.

In vehicular networking, the heavy traffic can cause channel congestion and hence, degrade the tracking accuracy of cooperative vehicle safety systems. To overcome this problem, a dynamic packet reception model that integrates the packets reception rate and the vehicle density is proposed. Then, a traffic-flow-based vehicle density estimation method is designed. This estimation method is capable of predicting the vehicle density in the scenario, where there exist strong interactions among the vehicles. Based on the vehicle density method, a dynamical transmission power control strategy is developed. This transmission power control strategy employs model predictive control to make the optimal control decisions based on the estimated vehicle density. Experimental analyses demonstrate that the dynamical power control strategy can greatly enhance the vehicle tracking performance of cooperative vehicle safety systems under dynamical traffic situation.

B2C is a commercial retail model of e-commerce for selling products and services directly to consumers. To solve the credit risk issues in B2C e-commerce, in this paper, a credit risk game mechanism is proposed based on game theory and logical Petri nets theory. First, by combining logical Petri nets with game theory, a theoretical modeling method called the logical game Petri nets is proposed. To characterize the utility that each body gained during the competition processes using the least square method, utility functions that describe the relationships between enterprises in different business modes are derived; next, a logical game Petri net model to specify the interactions among different bodies in the enterprise competition module is constructed. To analyze the behavior of the competition module, a reachable marking graph for this logical game Petri net model is established. According to this reachable graph, a utility matrix is subsequently designed to obtain the maximum expected utility for the bodies; finally, through analysis of the logical game Petri nets model for the enterprise competition module, the local optimal utility, as well as the global optimal utility of the individuals and groups, can be guaranteed.

The goal of this work was to use laboratory evolution assays and whole-genome sequencing to develop and test the safety of a probiotic, Lactobacillus plantarum, with high-level of resistance to gentamicin. The evolution of L. plantarum was evaluated under the selective pressure from gentamicin and subsequently when the selective pressure was removed. After 30 days of selective pressure from gentamicin, the minimum inhibitory concentration (MIC) of L. plantarum to gentamicin increased from 4 to 512 μg/mL and remained stable at this level. After removing the selective pressure, the resistance of L. plantarum to gentamicin decreased to 64 μg/mL after 20 days, and remained stable thereafter. Although the MIC declined it was still higher than the cut-off value recommended by EFSA, indicating that the acquisition of gentamicin-resistance was an irreversible process. Using whole-genome sequencing, gene mutations were identified in the strains that had undergone selection pressure from gentamicin as well as in the strains where the selection pressure was subsequently removed. Specifically, four non-synonymous mutations were detected including one single nucleotide polymorphism (SNP), one insertion, and two structural variants (SVs), of which the mutations in genes encoding the drug resistance MFS transporter and transcriptional regulator of AraC family were only detected in the strains under selective pressure from gentamicin. The results indicate that these mutations play an important role in increasing the resistant levels of L. plantarum to gentamicin. The mobility analysis of mutant genes confirmed that they were not located on mobile elements of the genome of highly resistant L. plantarum, indicating that horizontal gene transfer was not possible.

Plague, caused by Yersinia pestis, was classified as a reemerging infectious disease by the World Health Organization. The five human pneumonic plague cases in Yulong County in 2005 gave rise to the discovery of a Yulong plague focus in Yunnan province, China. Thereafter, continuous wild rodent plague (sylvatic plague) was identified as the main plague reservoir of this focus. In this study, the epizootics in Yulong focus were described, and three molecular typing methods, including the different region (DFR) analysis, clustered regularly interspaced short palindromic repeats (CRISPRs), and the multiple-locus variable number of tandem repeats (VNTR) analysis (MLVA) (14+12), were used for the molecular typing and source tracing of Y. pestis isolates in the Yulong plague focus. Simultaneously, several isolates from the vicinity of Yunnan were used as controls. The results showed that during the 10-year period from 2006 to 2016, an animal plague epidemic occurred in 6 of those years, and 5 villages underwent an animal plague epidemic within a 30-km2 area of the Yulong plague focus. Searching for dead mice was the most effective monitoring method in this plague focus. No positive sample has been found in 6937 captured live rodents thus far, suggesting that the virulence of strains in the Yulong plague focus is stronger and the survival time of mice is shorter after infection. Strains from Lijiang, Sichuan and Tibet were of the same complex based on a typing analysis of DFR and CRISPR. The genetic relationship of Y. pestis illustrated by MLVA "14+12" demonstrates that Tibet and Sichuan strains evolved from the strains 1.IN2 (Qinghai, 1970 and Tibet, 1976), and Lijiang strains are closer to Batang strains (Batang County in Sichuan province, 2011, Himalaya marmot plague foci) in terms of genetic or phylogenic relationships. In conclusion, we have a deeper understanding of this new plague focus throughout this study, which provides a basis for effective prevention and control.