Recent advances in biosynthesis mechanisms and yield enhancement strategies of erythritol.

Erythritol is a four-carbon sugar alcohol naturally produced by microorganisms as an osmoprotectant. As a new sugar substitute, erythritol has recently been popular on the ingredient market because of its unique nutritional characteristics. Even though the history of erythritol biosynthesis dates from the turn of the twentieth century, scientific advancement has lagged behind other polyols due to the relative complexity of making it. In recent years, biosynthetic methods for erythritol have been rapidly developed due to an increase in market demand, a better understanding of metabolic pathways, and the rapid development of genetic engineering tools. This paper reviews the history of industrial strain development and focuses on the underlying mechanism of high erythritol production by strains gained through screening or mutagenesis. Meanwhile, we highlight the metabolic pathway knowledge of erythritol biosynthesis in microorganisms and summarize the metabolic engineering and research progress on critical genes involved in different stages of the synthetic pathway. Lastly, we talk about the still-contentious issues and promising future research directions that will help break the erythritol production bottleneck and make erythritol production greener and more sustainable.

The regulatory effects of the apelin/APJ system on depression: A prospective therapeutic target.

Depression is a debilitating neuropsychological disorder characterized by high incidence, high recurrence, high suicide, and high disability rates, which poses serious threats to human health and imposes heavy psychological and economic burdens on family and society. The pathogenesis of depression is extremely complex, and its etiology is multifactorial. Mounting evidence suggests that apelin and apelin receptor APJ, which compose the apelin/APJ system, are related to the development of depression. However, the specific mechanism is still unclear, and research in this area in human is still insufficient. Acceleration of research into the regulatory effects and underlying mechanisms of the apelin/APJ system in depression may identify attractive therapeutic targets and contribute to the development of novel intervention strategies against this devastating psychological disorder. In this review, we mainly discuss the regulatory effects of apelin/APJ system on depression and its potential therapeutic applications.

Interactions between structure and function of resistant glucans for alleviating type 2 diabetes mellitus (T2DM) and its complications in mice.

Resistant glucan, a functional dietary fiber, has been shown to alleviate type 2 diabetes mellitus (T2DM) and its complications in clinical studies. However, the interactions between the special structure of resistant glucan and the metabolism-related pathways in T2DM have not yet been systematically studied. This study identified the structural differences between resistant glucans prepared by new and old methods. Oral gavage with two resistant glucans in T2DM mice, led to significant improvements in glucose and lipid metabolism as measured by related indicators (including gut microbiota, fecal metabolites, and physiological and biochemical indexes). According to these results, in addition to van der Waals forces, micelle formation, and hydrogen bonding, the branching structures of resistant glucans produced more hydroxyl, carbonyl, and keto groups that linked cholesterols, cholesterol esters, and low-density lipoprotein intermediates. Moreover, after lipid clearing, the metabolic environment was more conducive to the proliferation of specific gut microbiota (including Phascolarctobacterium, Prevotella, Butyricicoccus, Weissella, and Anaerostipes) with decreasing abundance ratios of Firmicutes and Bacteroides. This facilitated the synthesis of high-density lipoprotein, conversion of cholesterol into coprostanol, and production of short-chain fatty acids and bile acids. Our findings provide a foundation for comprehensive investigation of the structure of resistant glucan in the promotion and prevention of T2DM.

Rheological Properties and Kinetics of Gelation of Binary Polymers between Xanthan Gum and Locust Bean Gum.

The synergistic interaction and gelling kinetics between xanthan gum (XG) and locust bean gum (LBG) at different mass ratios (XG/LBG 9:1, 7:3, 5:5, 3:7, 1:9) were investigated using a rheometer. The results showed that the mixtures of XG and LBG induced gel formation, and the strongest gel structure was found for the mixture of XG/LBG 3:7 according to the yield stress, storage modulus (G'), and power law parameters. Temperature ramp studies indicated that heating destroyed the gels at 55~60 °C, while cooling induced the sol-gel transition at around 52 °C for all mixtures. Structure developing rate (SDR) curves showed that XG/LBG 3:7 exhibited the highest SDR during the cooling ramp among all the samples. Non-isothermal kinetic analysis demonstrated that the gelation process of XG/LBG mixtures during cooling included two steps: a high-temperature region (55~39 °C) needing higher activation energy (Ea, 111.97 to 199.20 kJ/mol for different mixtures) and a low-temperature region (39~20 °C) needing lower Ea (74.33 to 85.31 kJ/mol), which indicated higher energy barriers to overcome at the initial stage of gel formation. The lowest Ea of 74.33 kJ/mol was found for XG/LBG 3:7 in the low-temperature region. Scanning electron microscopy (SEM) showed that the gel of XG/LBG 3:7 presented the densest entanglements. These results indicated the strongest synergism interaction occurred in XG/LBG 3:7 to form gel network structures. This study will help promote the application of XG-LBG blends to design novel food structures.

Role of STAT3 and NRF2 in Tumors: Potential Targets for Antitumor Therapy.

Signal transducer and activator of transcription 3 (STAT3) and nuclear factor erythroid-derived 2-like 2 (NRF2, also known as NFE2L2), are two of the most complicated transcription regulators, which participate in a variety of physiological processes. Numerous studies have shown that they are overactivated in multiple types of tumors. Interestingly, STAT3 and NRF2 can also interact with each other to regulate tumor progression. Hence, these two important transcription factors are considered key targets for developing a new class of antitumor drugs. This review summarizes the pivotal roles of the two transcription regulators and their interactions in the tumor microenvironment to identify potential antitumor drug targets and, ultimately, improve patients' health and survival.

Preparation of resistant glucan by high pressure processing (HPP) and enzymatic methods increases indigestibility.

This study describes a new method for producing high-quality resistant glucan by characterizing the structural mechanism of indigestibility. The structures and properties of resistant glucans were characterized before and after in vitro simulated digestion. The results demonstrated that high-pressure processing (HPP) led to the complete disappearance of crystal peaks and increased the efficiency of the two enzymes (α-amylase and transglucosidase). Moreover, α-1,6 and ß-linkages were abundant in the connecting parts of the long and branching chains in the resulting resistant glucans, thus hindering the ability of digestive enzymes to hydrolyze short chains with a degree of polymerization (DP) ≤ 6. In addition, transglucosidase activity led to a higher proportion of short chains (DP 3-6), further promoting indigestibility. We demonstrated that, without rectification and decolorization, the dietary fiber content was >75 %, and the degree of branching increased to 50.9 %, indicating higher indigestibility than that resistant glucans produced by traditional methods.

Batch fermentation kinetics of acetoin produced by Bacillus subtilis HB-32.

OBJECTIVES: The aim of this work was to study the changes of bacterial cell growth, acetion formation and glucose consumption with fermentation time during batch cultivation. RESULTS: A mathematical model of cell growth, product synthesis, and substrate consumption changes with time during the batch cultivation of acetion was established. By analyzing the fitting curve of the kinetic model, it is found that the calculated value of the model fits well with the experimental value, and the fitting model R2 is greater than 0.98. CONCLUSIONS: The kinetic model established in this experiment can better reflect the batch cultivation process of acetion.

2-Keto-D-gluconic acid and prodigiosin producing by a Serratia marcescens.

Microbial fermentation has become the main method to produce target compound. In this study, a 2-Keto-D-gluconic acid (2-KGA) producing mutant strain was obtained by mutation with rational screening methods. Meanwhile, prodigiosin was produced when the nitrogen source in the medium was changed to peptone and its fermentation conditions were evaluated to achieve high-efficient accumulation. The mutant strain SDSPY-136 was firstly identified as Serratia marcescens by morphological observation and 16S rDNA sequencing. The 2-KGA synthetic capacity of S. marcescens SDSPY-136 was evaluated by shake fermentation with 110 g/L glucose as substrates. For fermentation, 2-KGA yield, conversation rate and purity of SDSPY-136 reached 104.60 g/L, 95.10%, 99.11% in 72 h. The red pigment was extracted from the fermentation broth using acidic methanol and identified as prodigiosin by FT-IR. The optimal conditions were as follows: glycerol 20 g/L, peptone 20 g/L, MgSO415 g/L, pH 6.0, a 2% (v/v) inoculum, 30 °C and 200 rpm of shaking culture. Eventually, prodigiosin reached a yield of 9.89 g/Lafter shake culturing for 50 h under this condition. The mutant S. marcescens SDSPY-136 was shown to be promising for 2-KGA and prodigiosin production and a suitable object for prodigiosin metabolism research of S. marcescens.

Effects of soluble dietary fibers on the viscosity property and digestion kinetics of corn starch digesta.

Four soluble dietary fibers (SDFs) were fortified with corn starch (CS) at different concentrations to match the same viscosity equivalents. The mixtures were subjected to a simulated digestion procedure to study the effects of SDFs on viscosity properties and digestion kinetics of CS. Results showed that SDFs increased the hydration property and decreased the water mobility of digesta. During digestion process, SDFs increased the apparent viscosity of digesta to some extent, and showed significant difference to delay the decay of digesta viscosity (kv). The amylolysis inhibitory ability was similar when each SDF was present at the same viscosity equivalent, however, significant differences were found on the digestion rate constant of k2. Linear correlations between kv and k2 were established for 1 and 2 equivalent groups. These results demonstrated that SDFs could delay the digestion process as chemistry differences, which related to their ability on delaying the change of digesta viscosity.

Evaluation of Reactivity of Monoclonal Antibodies Against Omp25 of Brucella spp.

Brucellosis is a serious zoonosis occurring mainly in developing countries, and its diagnosis is largely dependent on serologic detection and bacterial culture. In this study, we developed the murine monoclonal antibodies (mAbs) against a conserved and major outer membrane protein 25 (Omp25) of Brucella species (B. spp.) for use in clinical diagnosis. The mAbs to Omp25 were produced by hybridoma technique, which were utilized for developing various immunoassays for detection of Brucellae, including Western blot (WB), enzyme-linked immunosorbent assay (ELISA), immunochemical staining (ICS), immunofluorescence staining (IFS), and flow cytometry assay (FCM). A number of five mAbs (2B10, 4A12, 4F10, 6C12, and 8F3) specific to Omp25 were selected, including 2 IgG1, 2 IgG2a, and 1 IgG2b. Among them, mAbs 6C12, 8F3, and 4A12 reacted highly with B. melitensis (M5-90), B. abortus (S19, 104M, and 2308), and B. suis strain (S2). No cross-reactivity with Yersinia enterocolitica O:9, Salmonella spp., and Escherichia coli was found. By mapping Omp25 epitopes, mAb 6C12 was found as reacting with a semi-conformational epitope, and mAbs 4A12 and 8F3 as recognizing a different linear epitope, respectively. The paired mAbs were tested for detecting Brucella species, suggesting that 8F3 was suitable for solid phase capture and 6C12 or 4A12 was suitable for conjugation with HRP for detection of Brucella Omp25 in ELISA. The FCM was established by mAb 6C12 for detecting intracellular Brucellae-infected peripheral blood mononuclear cells (PBMCs) from brucellosis patients. In conclusion, mAbs against Omp25 are precious reagents for detection of Brucellae in clinical samples with various immunoassays. mAb 6C12-based FCM could be potentially used for the monitoring of therapeutic efficacy for brucellosis in clinical practice.

The Protective Effects and Mechanisms of Apelin/APJ System on Ischemic Stroke: A Promising Therapeutic Target.

The orphan receptor APJ and its endogenous ligand apelin, which are expressed in the brain, are the major components of the apelin/APJ system. Growing evidence shows that the apelin/APJ system plays a vital role in the pathophysiology of cerebral ischemic injury. Targeting the apelin/APJ system may have protective effects on cerebral ischemic injury. In this review, we sum up the latest research progress relating to the actions and therapeutic potential of the apelin/APJ system in ischemic stroke. An in-depth knowledge of the pathophysiological effects of the apelin/APJ system and the underlying mechanisms will help to develop novel therapeutic interventions for ischemic stroke.

Epidemic features of seasonal influenza transmission among eight different climate zones in Gansu, China.

BACKGROUNDS: Seasonal influenza remains epidemic globally with a substantial health burden. Understanding the transmission patterns and epidemic features of influenza may facilitate the improvement of preventive and control measures. This study aims to assess the epidemic features of influenza among different climate zones and identify high-risk zones across Gansu province, China. METHODS: We collected weekly influenza cases at county-level between 1st January 2012 and 31st December 2016, as well as climate zones classification shapefile data from Köppen-Geiger climate map. We compared the epidemic features (Frequency index (α), Duration index (ß) and Intensity index (γ)) of influenza among different climate zones. Spatial cluster analysis was used to examine the high-risk areas of transmission of influenza. RESULTS: The distribution of cases existed significant differences among eight climate zones (F-test: 267.02, p < 0.05). The highest mean weekly incidence rate (per 100,000 population) was 0.59 in snow climate with dry winter and warm summer (Dwb). The primary (relative risk (RR): 3.61, p < 0.001) and secondary (RR: 2.45, p < 0.001) clusters were located in Dwb. The highest values of α, ß and γ were 1.00, 261 and 154.38 in Dwb. The hot spots (high-high clusters) of the epidemic indices were detected in Dwb. CONCLUSIONS: This study found the variability of epidemic features of influenza among eight climate zones. We highlight that Dwb was the high-risk zone where influenza clustered with the highest incidence rate and epidemic temporal indices. This provide further insight into potential improvement of preventive measures by climate zones to minimize the impact of epidemics.

Interaction between barley ß-glucan and corn starch and its effects on the in vitro digestion of starch.

A ß-glucan was extracted from hull-less barley (HBBG) and its effects on the solution properties and in vitro digestion of corn starch (CS) were studied. Rheological results showed that HBBG diminished the gelling ability and increased the apparent viscosity of CS solution. The critical concentration was lowered from 1.10% (CS) to 0.48% (CS/HBBG mixture), and the slow relaxation component T22 decreased from 1417.47 to 464.16 ms after the incorporation of HBBG to CS solution. In vitro digestion study indicated that HBBG significantly increased the apparent viscosity of digesta and inhibited the starch hydrolysis and glucose diffusion. The entanglement and overlap formed by HBBG and CS interaction and aggregates of HBBG itself were considered to enhance the viscosity, thus limiting the water mobility of the system, reducing the contact of digestive enzyme with starch and diffusion of glucose to the small intestinal microvilli. This study suggests that HBBG can be recognized as an important ingredient in starch food to reduce postprandial glycemic responses.

Exopolysaccharide from Streptococcus thermophilus as stabilizer in fermented dairy: Binding kinetics and interactions with casein of milk.

Exopolysaccharides (EPSs) from lactic acid bacteria have great effect on the quality of fermented milk products. However, the mechanism for the quality improvement has not been well described. This study aimed to investigate the molecular binding kinetics and interactions between EPS obtained from Streptococcus thermophilus AR333 (EPS333) and casein of milk (CM) in a simulated acidifying process. The results indicated that EPS333 had a significant effect on the stability of casein micelles at acidic pH (6.0-4.5) according to the turbidity, ζ-potential, particle size and distribution analysis. The adsorption-desorption study by bio-layer interferometry identified the direct affinity binding between EPS333 and CM, the interactive moiety of casein was α-casein, rather than ß- or κ-casein. Fluorescence quenching analysis revealed that the force types of interaction between EPS333 and CM were dynamically changeable during the acidifying process, mainly from electrostatic interaction at pH 7.0-6.5, to hydrophobic or hydrogen bonding at pH 6.5-5.5, and then transferred to electrostatic interaction again at pH 5.5-5.0. Conclusively, EPS333 could bind with CM directly via different binding forces during acidifying process to stabilize the properties of casein micelles.

Telomere Length: A Potential Biomarker for the Risk and Prognosis of Stroke.

Stroke is one of the leading causes of death and disability worldwide. Age is associated with increased risk of stroke, while telomere length shortening plays a pivotal role in the process of aging. Moreover, telomere length shortening is associated with many risk factors of stroke in addition to age. Accumulated evidence shows that short leukocyte telomere length is not only associated with stroke occurrence but also associated with post-stroke recovery in the elderly population. In this review, we aimed to summarize the association between leukocyte telomere length and stroke, and discuss that telomere length might serve as a potential biomarker to predict the risk and prognosis of stroke.

Rheological properties of Prunus persica exudate: Potential effects of proteins and polyphenols.

This study was to investigate the rheological properties of graded Prunus persica exudates (peach gums). Graded peach gums were extracted by hot water and precipitated by ethanol to obtain white peach gum polysaccharide (WPGP) and yellow peach gum polysaccharide (YPGP). Chemical analysis showed that YPGP had 0.11% proteins and 0.23% polyphenols, which were not detected in WPGP. Molecular weight of WPGP and YPGP were determined as 6.09 × 103 kDa and 5.82 × 103 kDa, respectively, by using HPGPC. Monosaccharide analysis revealed that WPGP and YPGP were mainly composed of arabinose and galactose in an approximate molar ratio of 2: 1. These results suggested that WPGP and YPGP might have the same polysaccharide composition. Rheological analysis revealed that peach gum aqueous solutions (10% w/w) exhibited the non-Newtonian shear-thinning behavior and gel structure. Apparent viscosity and viscoelasticity of peach gums were slightly decreased in alkaline solution (pH = 11), high temperature (40 °C) and the presence of salt ions. YPGP solution possessed higher viscosity and storage modulus than WPGP solution at all the tested conditions, which suggested that conjugates of proteins and polyphenols might be involved in the gel network of YPGP solution, resulting in an increase in apparent viscosity.

Composition and Rheological Properties of Polysaccharide Extracted from Tamarind (Tamarindus indica L.) Seed.

A polysaccharide was extracted in high yield from tamarind (Tamarindus indica L.) seed (TSP) by acidic hot water extraction and ethanol precipitation. It was composed of 86.2% neutral polysaccharide, 5.4% uronic acid and 1.3% protein. The molecular weight of TSP was estimated to be about 1735 kDa, with glucose, xylose, and galactose in a molar ratio of 2.9:1.8:1.0 as the major monosaccharides. The steady shear and viscoelastic properties of TSP aqueous solutions were investigated by dynamic rheometry. Results revealed that TSP aqueous solution at a concentration above 0.5% (w/v) exhibited non-Newtonian shear-thinning behavior. Dynamic oscillatory analysis revealed that 10% (w/v) TSP showed as a "weak gel" structure. Apparent viscosities and viscoelastic parameters of TSP solutions decreased drastically in an alkaline solution of pH > 10, but slightly influenced by acidic solution, high temperature and the presence of salt ions and sucrose. These results indicated that TSP possessed excellent pH-resistance and thermo-stability, which might be suitable for applications in acidic beverages and high-temperature processed foodstuffs.

Ureter tissue engineering with vessel extracellular matrix and differentiated urine-derived stem cells.

OBJECTIVE: To assess the possibility of ureter tissue engineering using vessel extracellular matrix (VECM) and differentiated urine-derived stem cells (USCs) in a rabbit model. METHODS: VECM was prepared by a modified technique. USCs were isolated from human urine samples and cultured with an induction medium for the differentiation of the cells into urothelium and smooth muscle phenotypes. For contractile phenotype conversion, the induced smooth muscle cells were transfected with the miR-199a-5p plasmid. The differentiated cells were seeded onto VECM and cultured under dynamic conditions in vitro for 2 weeks. The graft was tubularized and wrapped by two layers of the omentum of a rabbit for vascularization. Then, the maturated graft was used for ureter reconstruction in vivo. RESULTS: VECM has microporous structures that allow cell infiltration and exhibit adequate biocompatibility with seeding cells. USCs were isolated and identified by flow cytometry. After induction, the urothelium phenotype gene was confirmed at mRNA and protein levels. With the combined induction by TGF-ß1 and miR-199a-5p, the differentiated cells can express the smooth muscle phenotype gene and convert to the contractile phenotype. After seeding cells onto VECM, the induced urothelium cells formed a single epithelial layer, and the induced smooth muscle cells formed a few cell layers during dynamic culture. After 3 weeks of omental maturation, tubular graft was vascularized. At 2 months post ureter reconstruction, histological evaluation showed a clearly layered structure of ureter with multilayered urothelium over the organized smooth muscle tissue. CONCLUSION: By seeding differentiated USCs onto VECM, a tissue-engineered graft could form multilayered urothelium and organized smooth muscle tissue after ureteral reconstruction in vivo. STATEMENT OF SIGNIFICANCE: Cell-based tissue engineering offers an alternative technique for urinary tract reconstruction. In this work, we describe a novel strategy for ureter tissue engineering. We modified the techniques of vessel extracellular matrix (VECM) preparation and used a dynamic culture system for seeding cells onto VECM. We found that VECM had the trait of containing VEGF and exhibited blood vessel formation potential. Urine-derived stem cells (USCs) could be differentiated into urothelial cells and functional contractile phenotype smooth muscle cells in vitro. By seeding differentiated USCs onto VECM, a tissue-engineered graft could form multilayered urothelium and organized smooth muscle tissue after ureteral reconstruction in vivo. This strategy might be applied in clinical research for the treatment of long-segment ureteral defect.

Enhanced itaconic acid production in Yarrowia lipolytica via heterologous expression of a mitochondrial transporter MTT.

Itaconic acid, a promising platform chemical, has been applied in many fields of industrial production. As a potential candidate for itaconic acid production, Yarrowia lipolytica possesses several innate abilities such as the tolerance of low-pH and high-shear stress, fast growth rate, cultivation flexibility, and easy for genetic manipulation. Here, Y. lipolytica Po1f which was tested to show high tolerance to itaconic acid could accumulate itaconic acid (0.363 g/L) by expressing the Aspergillus terreus cis-aconitic acid decarboxylase (CAD). Then, we tried to improve the supply and transport of the immediate precursor cis-aconitic acid by overexpressing a series of genes; these results indicate that overexpression of mitochondrial cis-aconitate transporter MTT is beneficial to the itaconic acid biosynthesis in Y. lipolytica. Further culture optimization enabled 22.03 g/L of itaconic acid to be produced in bioreactors, about 60-fold improvement over the initial titer, which is the highest itaconic acid production achieved at low pH by yeast reported worldwide, to data. This study demonstrates the great potential of Y. lipolytica as an industrial platform for itaconic acid production.