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Fructose is associated with colorectal cancer tumorigenesis and metastasis through ketohexokinase-mediated metabolism in the colorectal epithelium, yet its role in the tumor immune microenvironment remains largely unknown. Here, we show that a modest amount of fructose, without affecting obesity and associated complications, promotes colorectal cancer tumorigenesis and growth by suppressing the polarization of M1-like macrophages. Fructose inhibits M1-like macrophage polarization independently of fructose-mediated metabolism. Instead, it serves as a signal molecule to promote the interaction between hexokinase 2 and inositol 1,4,5-trisphophate receptor type 3, the predominant Ca2+ channel on the endoplasmic reticulum. The interaction reduces Ca2+ levels in cytosol and mitochondria, thereby suppressing the activation of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 1 (STAT1) as well as NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. Consequently, this impedes M1-like macrophage polarization. Our study highlights the critical role of fructose as a signaling molecule that impairs the polarization of M1-like macrophages for tumor growth. [Display omitted] • Fructose suppresses M1-like tumor-associated macrophage polarization • Fructose enhances the interaction between HK2 and ITPR3 in BMDMs • Fructose restrains inflammasome formation by regulating calcium flux • Macrophage GLUT5 expression positively relates to human colorectal cancer progression Yan et al. report that fructose promotes the progression of colorectal cancer by inhibiting M1-like tumor-associated macrophage polarization. Specifically, fructose functions as a signaling molecule, enhancing the interaction between HK2 and ITPR3, which disrupts intracellular calcium signaling, thereby impeding M1-like macrophage polarization. [ABSTRACT FROM AUTHOR]

• Propose the VGASM reliability evaluation concept for reliability assessment. • Develop the VGAK reliability evaluation method for multi-objective reliability estimation. • The VGAK reliability evaluation method is validated from mathematical and engineering aspects. • Provide valuable insight for the engineering structural systems reliability design. To effectively evaluate the multi-objective reliability of engineering structural systems, the vectorial generative adversarial surrogate modeling (VGASM) reliability evaluation concept is proposed by integrating the surrogate model, matrix theory, generate adversarial strategy, Copula thought, and linkage sampling technology. In this concept, the surrogate model is employed as a basis function; the matrix theory is applied to establish the vectors and cell arrays of variables and hyperparameters; the generate adversarial strategy is adopted to determine the hyperparameters; the Copula thought and linkage sampling technology are utilized to simultaneously implement multi-objective correlated reliability analysis. Under this concept, the vectorial generative adversarial Kriging (VGAK) reliability evaluation method is developed by combining the Kriging model with VGASM reliability evaluation concept. In addition, a mathematical example and two engineering cases (i.e., aeroengine exhaust gas temperature and turbine blisk multi-failures) are employed to validate the proposed method. The reliability devel of aeroengine exhaust gas temperature and turbine blisk are 0.9989 and 0.9984, when the allowable values of EGT, deformation, and strain are 950 °C, 1.9253 × 10−3 m, and 5.2898 × 10−3 m. Besides, the presented method holds excellent modeling and simulation properties by comparing multiple methods. The study can provide theoretical references for the multi-objective reliability evaluation of engineering structural systems. [ABSTRACT FROM AUTHOR]

• Identifying the filtering class of acceleration signals for HIC. • Quantitative analysis of the difference between rigid body HIC and centroid node HIC. • Enhancing the applicability of HIC by adjusting the injury thresholds in typical impact directions. Although the Head Injury Criteria (HIC) has been widely applied to assess head impact injuries, it faces two outstanding problems: 1) HIC is affected strongly by the cut-off frequency when processing acceleration signals. And these cut-off frequencies are experiential and lack unified guidelines; 2) If the head was impacted on a different part, should the corresponding HIC threshold be the same? If these problems are not resolved, it could potentially lead to a critical misinterpretation of the safety assessment. Finite element method was used to reconstruct head impacts. The head model includes tissues like skull, brainstem, cerebrospinal fluid, etc. The head model was impacted in the frontal, occipital, parietal or lateral direction with different impact velocities. Acceleration signals of the head model were extracted directly from the skull and the head centroid node. To obtain a robust HIC, the filtering class of acceleration signals were analyzed carefully. Then, the relation between rigid body HIC and the centroid node HIC were studied systematically. When the filtering class of rigid body acceleration and centroid node acceleration reached the cut-off frequency, the corresponding derivative of HIC tended to change smoothly. Using these cut-off frequencies, robust HICs were obtained. The rigid body HIC far exceeded that of centroid node HIC, such as 8, 9, 14 and 31 times exceeded in the frontal, occipital, parietal and lateral impact conditions, respectively. Moreover, approximate linear relations were found between the rigid body HIC and the centroid node HIC in different impact directions, respectively. From these relations, the injury thresholds of rigid body HIC of various directions were given quantitatively. The rational filtering class like CFC 800 and CFC 700 were given for rigid body HIC and centroid node HIC, respectively. The rigid body HIC had a significant discrepancy from the centroid node HIC. Linear relations between the rigid body HIC and centroid node HIC were found, and their slopes changed with impact directions. From these relations, we can adjust the injury thresholds reasonably if the head receives different impacts. These findings can effectively enhance the applicability of HIC. [ABSTRACT FROM AUTHOR]

Marrow mesenchymal stem cells (MSCs), especially bone MSCs (BMSCs), play a vital role in immunomodulation of graft rejection but many shortcomings limit its application. In this study, we aimed to investigate the modulation effect of MSCs from gingiva (GMSCs) on the rejection of rat liver transplantation model and to explore the potential mechanisms. GMSCs were obtained from human gingival tissues and BMSCs were harvested from Brown Norway (BN) rats. The siRNA that mediated knockdown of Fas ligand (FASL) expression in GMSCs (FASL-/-GMSCs) was transfected using lentivirus plasmid. Rat orthotopic liver transplantation model was established. The rats were divided randomly into four groups: normal saline (NS) group, FASL-/-GMSCs group, BMSCs group, and GMSCs group, all of which were injected the solution via dorsal vein of penis to construct the rat rejection model Graft survival and liver function indexes were measured. The immunological reactions of recipients including immune-cytokines, T-helper type 17 (Th17) and regulatory T cells (Treg) were also evaluated by flow cytometry. The graft survival of recipient rats in the GMSCs group was significantly prolonged in comparison with that of the NS, FASL-/-GMSCs and BMSCs group. GMSCs remarkably decreased the levels of AST, ALT and TBIL. As for immune-cytokines, serum levels of IL-2, IFN-γ and Th 17 in recipient rats from the GMSCs group reduced significantly compared with that of other three groups, while increased serum IL-10 and TGF-β expressions as well as peripheral serum Treg were also observed in GMSCs group. GMSCs exert immunoprotection on liver transplants by regulating FAS-FASL pathway. The current study firstly provides basis for GMSCs to be used in clinical anti-rejection after liver transplantation. [ABSTRACT FROM AUTHOR]

To effectively realize the reliability design of engineering structural system, a generative adversarial surrogate modeling (GASM) concept is proposed by innovating generative adversarial theory into surrogate modeling methods, which realize the aerospace engineering structural system reliability design adversarial modeling. In this concept, the surrogate model is adopted as a basis function to describe the functional relationship between input variables and output response; the generative adversarial theory is employed to obtain hyper-parameters of basis functions by continuous confrontation and evolution between the generation model and discrimination model. Under the GASM concept, the generative adversarial polynomial chaos expansion (GAPCE) method is developed to achieve aerospace engineering structural system reliability design. The effectiveness of presented GAPCE is verified by three examples including the nonlinear functions approximation, reliability design of flap deflection angle, and reliability estimation for turbine blisk radial deformation. The reliability level of flap deflection angle and turbine blisk radial deformation are 0.9998 and 0.9984, when the allowable values are 9° and 1.9222 × 10−3 m. Besides, the introduced approach possesses advantages of modeling performance (i.e., modeling accuracy and efficiency) and simulation properties (i.e., simulation precision and efficiency) by comparing with various methods. The efforts of this paper can provide a valuable reference for the operational safety of flap systems and engine structures and the development of reliability design theory. [ABSTRACT FROM AUTHOR]

• Propose AMS-MPCK for comprehensive reliability of structural systems. • Gain reliability of brake system temperature and blisk multi-failures. • AMS-MPCK holds advantages in modeling and simulation performance. • Provide valuable insight for the comprehensive reliability analyses. To effectively evaluate the comprehensive reliability of structural systems, the multi-polynomial chaos Kriging-based adaptive moving strategy (AMS-MPCK) is proposed, by integrating the moving least squares (MLS) method, adaptive equilibrium optimizer (AEO) algorithm, polynomial chaos expansions, Kriging model, synchronous modeling thought and linkage sampling technique. In this strategy, the MLS is adopted to select effective samples from training samples for modeling, the developed AEO algorithm is used to obtain the optimal local compact support region radius of MLS, the polynomial chaos expansions are applied to approximate the global behavior, the Kriging model is suited to manage the local variability of output response, the synchronous modeling thought is employed to realize the synchronous construction of multiple models, and the linkage sampling technology is utilized to obtain comprehensive output response values at the same time for improving the efficiency of reliability analysis. The accuracy and efficiency advantages of the proposed AMS-MPCK are verified by the benchmark functions approximation problems, the landing gear brake system temperature, and aeroengine turbine blisk multi-failures. Besides, the developed AMS-MPCK holds excellent modeling and simulation performance by comparing with different methods. The efforts of this study provide valuable insight into the comprehensive reliability analyses of mechanical structure systems. [ABSTRACT FROM AUTHOR]

• Develop vectorial modeling concept for multi-objective modeling. • Propose the AHVSMF for multi-objective reliability estimation. • The AHVSMF is verified form the viewpoint of mathematics and engineering. • Provide a useful way for multi-objective reliability analysis. Vectorial modeling concept is proposed in this paper by introducing the matrix theory into the point modeling concept (surrogate modeling strategy), and an adaptive vectorial surrogate modeling framework (AVSMF, short for) is developed based on the vectorial modeling concept and adaptive modeling strategy. Herein, the adaptive modeling strategy is adopted to determine the form of mathematical model of each objective in line with the cost function, the surrogate modeling strategy is regarded as the basis function for reflecting the relationship of the output of single-objective between the relevant inputs, and the matrix theory is used to ascertain the vectors and cell arrays of undetermined parameters and to establish the performance function of multi-objective structures. To validate the proposed method, we use three examples including approximate and probabilistic analysis of nonlinear function with multiple responses, reliability evaluation of landing gear brake system temperature and reliability assessment of aeroengine high-pressure turbine blisk stress, strain and deformation, to demonstrate the effectiveness of the developed AVSMF. Besides, the modeling and simulation properties are verified by comparison of different methods. The results show that the proposed AVSMF has obvious advantages in the computational efficiency and precision. [ABSTRACT FROM AUTHOR]

PH domain leucine-rich repeats protein phosphatase 1(PHLPP1) belongs to a novel family of Ser/Thr protein phosphatases: PHLPP serves as tumor suppressor in several cancers. However, little knowledge about the expression of PHLPP1 in human glioma tumor tissue and its role in inflammation response in glioma cells was known. Glioma samples were obtained from a total of 37 patients including 16 males and 21 females with surgical removal of the brain tumor. PHLPP1 protein and inflammatory cytokines were measured by Western blot analysis and immunohistochemistry while mRNA was determined by RT-PCR. The levels of inflammatory cytokines including TNF-α, IL-17, IL-1β in U251 glioma cells were evaluated by siRNA PHLPP1 and PHLPP1 addition. The loss of PHLPP1 expression occurs at high frequency in human gliomas. The highest mean values of PHLPP1 mRNA and protein were found in non-glioma brain tissues whereas the lowest mean values were found in those in glioblastoma with an increase of TNF-α, IL-17, IL-1β (p < 0.05). PHLPP1 expression in human glioma was associated negatively with the severity of the tumor and inflammatory cytokines. siRNA PHLPP1 could increase the levels of inflammatory cytokines in U251 glioma cells while PHLPP1 addition could inhibit significantly inflammatory cytokines. We concluded that PHLPP1 played a suppression role in inflammatory response of glioma. The present study indicated that PHLPP1 could be used as a predictor for the prediction of the patients or as a therapeutic target for the treatment of human glioma. [ABSTRACT FROM AUTHOR]

To meet the ever-increasing demand for detection of genetically modified crops (GMCs), low-cost, high-throughput and high-accuracy detection assays are needed. The new multiplex asymmetric polymerase chain reaction and asymmetric hyper-branched rolling circle amplification coupled with reverse dot blot (RDB) systems were developed to detect GMCs. Thirteen oligonucleotide probes were designed to identify endogenous targets ( Lec1 , Hmg and Sad1 ), event-specific targets ( RRS-5C , RRS-3C , Bt176 - 3C and MON810 - 3C ), screening targets ( 35S promoter and NOS terminator), and control targets ( 18S and PLX ). Optimised conditions were as follows: tailed hybridization probes (1–2 pmol/l) were immobilized on a membrane by baking for 2 h, and a 10:1 ratio of forward to reverse primers was used. The detection limits were 0.1 μg/l of 2% RRS and 0.5 ng/l of DNA from genetically modified (GM) soybean. These results indicate that the RDB assay could be used to detect multiplex target genes of GMCs rapidly and inexpensively. [ABSTRACT FROM AUTHOR]

Plectasin, the first fungus-derived defensin from Pseudoplectania nigrella , is considered to be one of the most likely substitutes for antibiotics used to cure Staphyloccocus and Streptococcus infections. Recombinant expression of plectasin in Pichia pastoris X-33 was achieved. In this work, we aimed to develop a multi-copy gene cassette to enhance plectasin expression in P. pastoris . Expression vectors pPICZαA-Pn ( n = 1, 2, 4, or 8) harboring a one, two, four, or eight-copy gene cassette were constructed and confirmed by digestion with Bam HI and Bgl II. Vectors linearized by Bgl II were transformed into P. pastoris by electroporation. The gene copy number of the recombinants was quantified by real-time quantitative PCR. Yields of recombinant plectasin were 296, 409, 516, and 879 mg/L for the 1-, 2-, 4-, and 8-copy transformants, respectively, in a 5-L fermentor, demonstrating that an increase in copy number results in a proportional elevation in the expression level of recombinant plectasin. The purity of plectasin was 90.8%, and the yield was found to be 814 mg/L using ion-exchange chromatography. Multi-copy gene dosage enhances plectasin expression levels and highly reduces its production cost. Additionally, the above results could be helpful in improving the application and understanding of the P. pastoris expression system. [ABSTRACT FROM AUTHOR]

• Propose IWKMEF for dynamic reliability estimation of complex structures. • Gain reliability level 0.9984 for turbine blisk radial deformation. • IWKMEF has high simulation efficiency and precision. • Provide a useful insight for the dynamic reliability analysis of complex structure. To improve the dynamic reliability analyses of complex structures, intelligent weighted Kriging-based moving extremum framework (IWKMEF) is developed by absorbing moving least squares (MLS) thought, Gaussian weight, particle swarm optimization (PSO) method and Kriging model into extremum response surface method (ERSM). ERSM method is employed to convert the dynamic output response into extremum values. MLS thought is used to find effective samples. Gaussian weight is to improve modeling precision. PSO method is applied to optimize the local compact support region radius of MLS. The radial deformation of turbine blisk is conducted to verify the effectiveness of IWKMEF method. The results show that the reliability degree of turbine blisk is 0.9984 when the allowable value is 1.9217 × 10−3 m; The developed IWKMEF holds high performance by comparing direct simulation, ERSM and traditional Kriging model. The efforts of this study provide a useful insight for the dynamic reliability analysis of complex structure. [ABSTRACT FROM AUTHOR]

Highlights: [•] First report of cloning of a novel AP gene from Saccharomyces boulardii. [•] Heterologous expression of high-activity rAP in Pichia pastoris X-33. [•] rAP possess favorable enzymatic characters. [•] rAP possess the function of dephosphorylation of LPS. [•] rAP alleviate inflammation responses caused by LPS. [Copyright &y& Elsevier]

Abstract: The emergence of bacterial resistance to common antibiotics poses a threat to human health and has rekindled an interest in antimicrobial peptides (AMPs). LHP7, a novel hybrid AMP containing 83 amino acid residues was designed on the basis of the LH28 and plectasin. LHP7 was expressed in Pichia pastoris, the total concentration of secreted protein reached 0.906g/L after 108h of methanol induction. Its antimicrobial activity was higher than that of the parent AMPs; the minimal inhibitory concentrations (MICs) of LHP7 against Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus suis were 0.091, 0.023 and 0.18μM, respectively. The antibacterial activity of LHP7 against clinical MRSA isolates (MICs=0.73–2.91μM) was enhanced over that of plectasin. The fractional inhibitory concentration (FIC) indicated a synergistic effect between LHP7 and ampicillin against MRSA (FIC=0.375), and combinations of LHP7 with gentamicin, rifampin or tetracycline provided evidence of additive effects (FIC=0.625–1.0). LHP7 exhibited a broad range of pH stability and thermostability, and a hemolytic activity of less than 5% below a concentration of 500μg/mL. It was resistant to pepsin and papain digestion, but sensitive to trypsin digestion. These results suggest that LHP7 might have potential as a broadly applied and clinically useful antimicrobial agent. [Copyright &y& Elsevier]

Abstract: Although many literatures have shown that prolonged high-dose administration of corticosteroids is hazardous and not indicated to therapy acute lung injury (ALI), there is little information on the harmful effect of prolonged high-dose corticosteroids in acute lung injury. In this study, we aimed to investigate the effect of prolonged high-dose methylprednisolone (MPL) on ALI and improve knowledge regarding the appropriate use of corticosteroids in ALI. The different doses of MPL (3, 30, 180mg·kg−1) were given via tail vein injection 1h after the first time LPS administration and were daily administrated for 14days. Lung tissues and lavage samples were isolated for biochemical determinations and histological measurements at 12h, 7days and 14days after LPS administration. Single administration of 180mg·kg−1 MPL decreased the lung injury score, wet-to-dry ratio, the total cell numbers and level of procollagen type III in BALF at 12h after LPS challenge. However, prolonged therapy with 180mg·kg −1 MPL for 7days and 14days decreased the number of AMs in BALF and increased the above-mentioned indexes. These results suggested that the prolonged high-dose MPL has harmful effects to treat LPS-induced ALI in rats. [Copyright &y& Elsevier]

Abstract: LAMP–LFD, loop-mediated isothermal amplification (LAMP) combined with a lateral-flow dipstick (LFD), was developed and evaluated as a new method for the detection of Roundup Ready soybean (RRS). Biotinylated LAMP amplicons were produced by two sets of six designed primers that specifically recognized the endogenous gene (Lec1) and the event-specific 5′ -junction region (G35S) of RRS followed by hybridization with FITC-labeled probes and LFD detection. The following optimized conditions for the LAMP assay were used: deoxynucleotide triphosphate (dNTP) concentrations ranging from 0.6 to 3.2 mM, 6 mM Mg2+, 4 U Bst DNA polymerase and a 1:6 ratio of outer to inner primers. The LAMP–LFD results were generated within 50 min. The detection limit of LAMP–LFD was 2.4 copies of the linearized plasmid pTLH10 and was 20 times more sensitive than conventional PCR. We demonstrated the high specificity of LAMP–LFD by testing processed soybean products, genetically modified (GM) maize and Bt-cotton meal. The novel LAMP–LFD setup presented here is simple, rapid, and has the potential for future use in the detection of GM ingredients in feed and food products. [Copyright &y& Elsevier]

Abstract: The alpha subunit of β-conglycinin is one of the main allergens found in soybeans. For the preparation of a specific monoclonal antibody (mAb) against the α subunit, potential epitopes were predicted using Protean and evaluated by Wu''s Antigenic Index. The specific epitope 85EQDERQFPFPR95 was synthesized, and then conjugated to keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA) for use as an immunogen and the plate-coating antigen, respectively. The resulting mAb, termed mAb-60K, was characterized as belonging to the IgG1 isotype and containing the κ light chain; it exhibited high specificity for the α subunit and did not cross react with the α′ and β subunits of β-conglycinin or other proteins found within soybeans. A competitive enzyme-linked immunosorbent assay (cELISA) with high accuracy and reproducibility was developed based on mAb-60K and the plate-bound peptide. Co-incubation with the full-length α subunit showed a 50% mAb binding inhibition concentration (IC50) value of 4.42ng/mL, with a linear inhibition curve observed α subunit concentrations between 0.65 and 29.84ng/mL. The newly developed mAb-60K and the companion cELISA could provide a valuable tool for determining sensitivity towards the α subunit of soybean β-conglycinin and for future studies on food allergies resulting from this protein. [Copyright &y& Elsevier]

Abstract: The nutritional quality of soybean meal (SBM) was improved via solid-state fermentation using the Aspergillus oryzae or Bacillus subtilis microbes in conical flasks. Compared to the control, the protein content in fermented soybean meal (FSBM) was increased by 8.37% and 0.34% with B. subtilis and A. oryzae, respectively, and their trypsin inhibitor contents were reduced by 96% and 82%, respectively. Furthermore, the concentrations of small-size proteins in FSBM were increased from 5% to 63% and from 5% to 35% by B. subtilis and A. oryzae, respectively, while the concentrations of large-size proteins were reduced from 40% to 2% and from 40% to 8%, respectively. Significantly lower levels of antigenic proteins were observed in FSBM compared to SBM. Also, FSBM exhibited a higher level of DPPH free radical-scavenging activity than did the control. The in vitro digestibility of crude protein by pepsin (IVDI) was increased strongly by fermentation. Fermentation with B. subtilis mediated a higher IVDI than did fermentation with A. oryzae. However, the in vitro digestibility of crude protein by pepsin and trypsin (IVDII) derived from B. subtilis and A. oryzae showed no significant difference from that of the control. In general, the protein content and anti-oxidation activity were increased and trypsin inhibitors and antigenic proteins were reduced in FSBM culture, indicating that it could be used as a new protein source in animal diets. [Copyright &y& Elsevier]

Abstract: Plectasin is the first known fungal defensin with potent activity against Gram-positive bacteria. To evaluate the potential therapeutic application of plectasin, we produced plectasin and investigated its solubility, activity and factors that affect its antimicrobial activity. Recombinant plectasin was produced from Escherichia coli in high yield by integration of fusion expression and on-column cleavage. Including 0.5M arginine significantly increased the solubility of plectasin in acetic acid buffer with 10% glycerol from 89μg/ml to 408μg/ml. Plectasin was soluble at 846μg/ml in Tris–glycerol–EDTA buffer. Plectasin was active against Gram-positive bacteria Streptococcus pneumoniae and Staphylococcus aureus with minimum inhibitory concentrations of 2 and 0.5μg/ml. Much lower or no activity was observed toward Gram-negative bacteria and fungi. Plectasin (128μg/ml) did not exhibit hemolytic activity toward rabbit erythrocytes. The activity of plectasin toward S. aureus was decreased by reduction with dithiothreitol, indicating that the disulfide-bond is essential for maximal activity. Plectasin was bactericidal under physiological concentrations of mono- and divalent cations. This activity was markedly attenuated by divalent cations in a concentration-dependent manner, however, with complete inhibition occurring at Ca2+ concentrations greater than 25mM. These results suggested that the presence of the disulfide-bond and the absence of divalent cations play key roles in the antimicrobial activity of plectasin. [Copyright &y& Elsevier]

Abstract: A novel injectable in situ cross-linked hydrogel has been designed via Michael type addition between thiol-modified chitosan (CS–NAC) and PEG diacrylate (PEGDA). Hydrogel was rapidly formed in situ under physiological conditions. The gelation time depended on the content of free thiols in CS–NAC, temperature, and concentration of CS–NAC and PEGDA. Thermogravimetric analysis showed the thermal stabilities of hydrogels. SEM observation results confirmed a porous 3D structure. Rheological studies showed that the cross-linking density and elasticity of hydrogel had a correlation to the content of CS–NAC and PEGDA. Swelling studies revealed that these hydrogels had a high initial swelling and were degradable under physiological conditions. And swelling was highly temperature-dependent and was directly related to the amount of cross-linking. Biological activities of the hydrogels were evaluated by in vitro cell compatibility on HDFs and A549 cells and the results indicated that the hydrogel was biocompatible. [Copyright &y& Elsevier]

• Probiotics have different physiological functions on immune and microecology. • There are two types of probiotics resistance to antibiotics: intrinsic and acquired. • Probiotics develop antibiotic resistance by gene mutation or horizontal gene transfer. • Probiotics have potential risks-pathogenicity and antibiotic resistance gene transfer. Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit upon the host. At present, probiotics are gaining popularity worldwide and are widely used in food and medicine. Consumption of probiotics is increasing with further in-depth research on the relationship between intestinal flora and host health. Most people pay more attention to the function of probiotics but ignore their potential risks, such as infection and antibiotic resistance transfer to pathogenic microbes. Physiological functions, effects and mechanisms of action of probiotics were covered in this review, as well as the antibiotic resistance phenotypes, mechanisms and genes found in probiotics. Typical cases of antibiotic resistance of probiotics were also highlighted, as well as the potential risks (including pathogenicity, infectivity and excessive immune response) and corresponding strategies (dosage, formulation, and administration route). This timely study provides an avenue for further research, development and application of probiotics. [ABSTRACT FROM AUTHOR]

• STMF is developed for system reliability analysis considering failure correlation. • The joint optimum of empirical risk and expected loss is realized by MSM of STMF. • The correlation measurement hierarchy is established by MTM of STMF. • STMF is verified by analysis of turbine bladed disk. • STMF holds superior accuracy and efficiency in reliability analysis. To improve the efficiency and accuracy of complex system reliability analysis considering failure correlation, a selective transmit modeling framework (STMF) is proposed by integrating multi-stage selective modeling (MSM) strategy with multi-failure transmit modeling (MTM) architecture. In MSM, the modeling quality of multi-learner is discussed to establish the optimal functional relationship between multi-variable and multi-response by considering the suitability of modeling samples, and the fitting performance of copula functions is quantified to construct the optimal correlation model between multi-failure through distance measure. For MTM, the correlation sequence measurement structure of multiple modes is established to construct the joint reliability analysis model of complex structure by updating iteratively the margin distribution functions with the strongest correlation. Taking the turbine bladed disk as study object, the validation of the proposed STMF is verified by comparing with other methods. The analytical results of study case can be expressed as that (i) STMF holds the superior performance in modeling accuracy and time-consuming, at 2.6308 × 10-2 and 0.4638 s respectively; (ii) STMF also has the best property in simulation, separately at 2.2123 s in simulation efficiency and at 99.9899 % in simulation precision; (iii) the reliability 0.9876 of study case obtained by STMF is higher than the reliability 0.9855 that depends on the mutual independence assumption. The effort of this work is prominent to promote effectively the quantification of multi-failure correlation and the improvement of reliability analysis performance for complex systems. [ABSTRACT FROM AUTHOR]