Production of optically pure 2,3-butanediol from Miscanthus floridulus hydrolysate using engineered Bacillus licheniformis strains.

2,3-Butanediol (2,3-BD) can be produced by fermentation of natural resources like Miscanthus. Bacillus licheniformis mutants, WX-02ΔbudC and WX-02ΔgldA, were elucidated for the potential to use Miscanthus as a cost-effective biomass to produce optically pure 2,3-BD. Both WX-02ΔbudC and WX-02ΔgldA could efficiently use xylose as well as mixed sugars of glucose and xylose to produce optically pure 2,3-BD. Batch fermentation of M. floridulus hydrolysate could produce 21.6 g/L D-2,3-BD and 23.9 g/L meso-2,3-BD in flask, and 13.8 g/L D-2,3-BD and 13.2 g/L meso-2,3-BD in bioreactor for WX-02ΔbudC and WX-02ΔgldA, respectively. Further fed-batch fermentation of hydrolysate in bioreactor showed both of two strains could produce optically pure 2,3-BD, with 32.2 g/L D-2,3-BD for WX-02ΔbudC and 48.5 g/L meso-2,3-BD for WX-02ΔgldA, respectively. Collectively, WX-02ΔbudC and WX-02ΔgldA can efficiently produce optically pure 2,3-BD with M. floridulus hydrolysate, and these two strains are candidates for industrial production of optical purity of 2,3-BD with M. floridulus hydrolysate.

Assessment of Tumor Stiffness With Shear Wave Elastography in a Human Prostate Cancer Xenograft Implantation Model.

OBJECTIVES: To investigate the stiffness of human prostate cancer in a xenograft implantation model using shear wave elastography and compare the pathologic features of tumors with varying elasticity. METHODS: Human prostate cancer DU-145 cells were injected into 24 nude male mice. The mice were divided into 3 groups according to the time of transplantation (6, 8, and 10 weeks). The volume, elasticity, and Young modulus of tumors were recorded by 2-dimensional sonography and shear wave elastography. The tumors were collected for pathologic analyses: hematoxylin-eosin staining, Ponceau S, and aniline staining were used to stain collagen and elastic fibers, and picric acid-sirius red staining was used to indicate type I and III collagen. The area ratios of collagen I/III were calculated. The correlation between the Young modulus of the tumor and area ratio of collagen I/III were evaluated. Immunohistochemistry of vimentin and α-smooth muscle actin was performed. RESULTS: Nineteen tumors in 3 groups were collected. The volume and mean Young modulus increased with the time of transplantation. There were more collagen fibers in the stiff tumors, and there were significant differences in the area ratios of collagen I/III between groups 1 (mean ± SD, 0.50 ± 0.17) and 3 (1.97 ± 0.56; P < .01). The Young modulus of the tumors showed a very significant correlation with the area ratios of collagen I/III (r = 0.968; P < .05). The expression level of α-smooth muscle actin protein was higher in group 3 than in the other groups, but differences in vimentin expression were barely seen. CONCLUSIONS: Shear wave elastography is a novel useful technology for showing the elasticity of human prostate cancer xenograft implantation tumors. Collagen fibers, especially collagen type I, play a crucial role in the elasticity in the human prostate cancer xenograft implantation model.

Secure control for remote networked stochastic systems via integral sliding mode.

This paper deals with the secure control problem for a class of networked stochastic systems with false data injection attacks via an integral sliding mode control technique. The networked control system is with a hierarchical structure, and the main controller and a remote controller are considered to realize the secure control against false data injection attacks on the network between a main controller and the plant. A mode-shared event-triggering controller is designed as the main controller, by utilizing a time delay approach. An input-output model based on a two-term approximation is applied to cope with the formulated time-varying delay. Then, the scaled small gain theory is employed to analyze the stability of the resulting system. Sufficient conditions on ensuring the desired system performance are derived and then the controller parameters are synthesized. Moreover, an elaborated sliding mode control law is proposed for the desired secure control action. Finally, two simulation examples are permitted to verify the effectiveness of the theoretical derivations.

A critical role for host-derived cystathionine-ß-synthase in Staphylococcus aureus-induced udder infection.

Cystathionine-ß-synthase (CBS) catalyzes the first step of the transsulfuration pathway. The role of host-derived CBS in Staphylococcus aureus (S. aureus)-induced udder infection remains elusive. Herein, we report that S. aureus infection enhances the expression of CBS in mammary epithelial cells in vitro and in vivo. A negative correlation is present between the expression of CBS and inflammation after employing a pharmacological inhibitor/agonist of CBS. In addition, CBS achieves a fine balance between eliciting sufficient protective innate immunity and preventing excessive damage to cells and tissues preserving the integrity of the blood-milk barrier (BMB). CBS/H2S reduces bacterial load by promoting the generation of antibacterial substances (ROS, RNS) and inhibiting apoptosis, as opposed to relying solely on intense inflammatory reactions. Conversely, H2S donor alleviate inflammation via S-sulfhydrating HuR. Finally, CBS/H2S promotes the expression of Abcb1b, which in turn strengthens the integrity of the BMB. The study described herein demonstrates the importance of CBS in regulating the mammary immune response to S. aureus. Increased CBS in udder tissue modulates excessive inflammation, which suggests a novel target for drug development in the battle against S. aureus and other infections.

Stabilization With Prescribed Instant for High-Order Integrator Systems.

This article develops a new controller design approach to stabilize system states onto the equilibrium at an arbitrarily selected time instant irrespective of the initial system states and parameters. By the stabilization approach, the actual convergence time (not the bound of actual convergence time) is independent of the initial value of system states. This feature differentiates our proposed prescribed-instant stability from conventional fixed, predefined, and prescribed time stability. In this work, we propose the controller design method for the prescribed-instant stability of n -order integrator systems. The proposed control is bounded and can gradually go to zero at an arbitrarily selected time instant, at which the system states reach zero simultaneously. This special stability of the controlled system is analyzed by reduction to absurdity. In simulations, an example of comparison with frequently used prescribed-time control is presented to show the difference. Moreover, the proposed stabilization method is validated by a magnetic suspension system with matched disturbances.

Study on the Effect of Borehole Size on Gas Extraction Borehole Strength and Failure Mode.

In the coal mine industry, the instability failure of an extraction borehole is one of the main factors leading to the decrease in gas extraction rate. The study on borehole strength and failure mode with different sizes can provide a theoretical basis for the optimization and selection of a gas extraction borehole. In this paper, biaxial loading tests are carried out on similar coal specimens, and the prediction model of borehole strength is proposed and verified. At the same time, numerical simulation of similar specimens is carried out to analyze the failure process of boreholes of different sizes. The results show that hole size has a great influence on hole strength, and the hole strength decreases with an increase of hole size. Size change has a great influence on the strength of a small-size borehole, and the strength of the borehole gradually stabilizes with an increase of size. The process of borehole failure can be divided into three stages, borehole top failure, borehole deformation, and crack extension. Stress concentration and a large number of cracks occur on the two wings of the borehole, and these cracks reduce the strength of the borehole. The stress concentration area of the borehole is X-shaped distribution, and the through crack mainly extends along this area and leads to the failure of the specimen.

Research on the Effect of Extinction Characteristics of Coal Dust on Visibility.

A good knowledge of the reduction mechanism of visibility is fundamental to developing preventive strategies in coal mines. In this work, the Mie theory was selected for investigating the absorption and scattering of coal dust. A prediction model for evaluating the visibility was developed based on the extinction characteristics of coal dust. The optical properties have been discussed to simplify the model and clarify the relationships among the different wavelengths and diameters. Additionally, the variety of extinction coefficients can be reasonably used in guiding the calculated visibility under different conditions. The experimental results demonstrated that the reduction of visibility was attributed to the synergistic effect of the extinction of coal dust and droplet. For the field application of this prediction model, the relative errors of the calculated and measured visibility were 9.8 and 7.1% from models I and II, which reflected the small deviation between the two methods. The prediction model can accurately describe the visibility in mines due to coal dust pollution. The exploration results provide a significant reference for the development and application of air cleaning technology for increased visibility.

Aconitine: A review of its pharmacokinetics, pharmacology, toxicology and detoxification.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitine, a C19-norditerpenoid alkaloid, derives from many medicinal plants such as Aconitum carmichaelii Debx. (Chinese:), Aconitum kusnezoffii Reichb (Chinese:), which were used to rheumatic fever, painful joints and some endocrinal disorders. AIMS OF THE REVIEW: The present paper reviews research progress relating to the pharmacokinetics, physiological and pathological processes of aconitine, while some promising research direction and the detoxification of aconitine are also discussed. MATERIALS AND METHODS: The accessible literature on aconitine, from 1990 to 2020, obtained from published materials of electronic databases, such as SCI finder, PubMed, Web of Science, Science Direct, Springer and Google Scholar was systematically analyzed. RESULTS: In this review, we address the pharmacokinetics of aconitine, as well as its pharmacological effects including anti-cancer, anti-inflammatory, anti-virus, immunoregulation, analgesic, insecticide and inhibition of androgen synthesis. Further, we summarize the toxicity of aconitine such as cardiotoxicity and neurotoxicity, on which we strikingly focus on the ways to reduce the toxicity of aconitine based. CONCLUSIONS: Aconitine plays an vital role in a wide range of physiological and pathological processes and we can reduce the toxicity of aconitine by compatibility and hydrolysis. Although some issues still exist, such as the correlative relationship between the dose and toxicity of aconitine not being clear, our review may provide new ideas for the application of aconitine in the treatment of related diseases.

Qing-Re-Xiao-Zheng Formula Modulates Gut Microbiota and Inhibits Inflammation in Mice With Diabetic Kidney Disease.

Evidence indicates that the metabolic inflammation induced by gut microbiota dysbiosis contributes to diabetic kidney disease. Prebiotic supplementations to prevent gut microbiota dysbiosis, inhibit inflammatory responses, and protect the renal function in DKD. Qing-Re-Xiao-Zheng formula (QRXZF) is a Traditional Chinese Medicine (TCM) formula that has been used for DKD treatment in China. Recently, there are growing studies show that regulation of gut microbiota is a potential therapeutic strategy for DKD as it is able to reduce metabolic inflammation associated with DKD. However, it is unknown whether QRXZF is effective for DKD by regulating of gut microbiota. In this study, we investigated the reno-protective effect of QRXZF by exploring its potential mechanism between gut microbiota and downstream inflammatory pathways mediated by gut-derived lipopolysaccharide (LPS) in the kidney. High-fat diet (HFD) and streptozotocin injection-induced DKD mice model was established to assess the QRXZF effect in vivo. Mice treated with QRXZF for 8 weeks had significantly lower levels of urinary albumin, serum cholesterol and triglycerides. The renal injuries observed through histological analysis were attenuated as well. Also, mice in the QRXZF group had higher levels of Zonula occludens protein-1 (ZO-1) expression, lower levels of serum fluorescein-isothiocyanate (FITC)-dextran and less-damaged colonic mucosa as compared to the DKD group, implying the benefit role for the gut barrier integrity. QRXZF treatment also reversed gut dysbiosis and reduced levels of gut-derived LPS. Notably, the expression of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB), which are important inflammation pathways in DKD, were suppressed in the QRXZF groups. In conclusion, our results indicated that the reno-protective effects of QRXZF was probably associated with modulating gut microbiota and inhibiting inflammatory responses in the kidney.

Modulation of the Gut Microbiota by Shen-Yan-Fang-Shuai Formula Improves Obesity Induced by High-Fat Diets.

Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier and chronic inflammation. Shen-Yan-Fang-Shuai formula (SYFSF) is a traditional Chinese herbal formula composed of Astragali Radix, Radix Angelicae Sinensis, Rheum Officinale Baill, and four other herbs. In this study, we identified that SYFSF treatment prevented weight gain, low-grade inflammation and insulin resistance in high-fat diet (HFD)-fed mice. SYFSF also substantially improved gut barrier function, reduced metabolic endotoxemia, as well as systemic inflammation. Sequencing of 16S rRNA genes obtained from fecal samples demonstrated that SYFSF attenuated HFD-induced gut dysbiosis, seen an decreased Firmicutes to Bacteroidetes ratios. Microbial richness and diversity were also higher in the SYFSF-treated HFD group. Furthermore, similar therapeutic effects and changes in gut microbiota profile caused by SYFSF could be replicated by fecal microbiota transfer (FMT). Taken together, our study highlights the efficacy of SYFSF in preventing obesity and related metabolic disorders. Its therapeutic effect is associated with the modulation of gut microbiota, as a prebiotic.

Application of Herbal Medicines with Heat-Clearing Property to Anti-Microinflammation in the Treatment of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a global pandemic, and microinflammation has been reported as an important pathogenic factor of DKD. Traditional Chinese Medicine (TCM) has been used in the treatment of DKD for thousands of years, and modern Chinese medicine studies have found that herbal medicines with heat-clearing property have a curative anti-inflammation effect in DKD. This article reviews the new clinical and experimental progress made in herbal medicines with heat-clearing property, in the treatment of DKD, as well as their safety aspects.

Filtering of Interval Type-2 Fuzzy Systems With Intermittent Measurements.

In this paper, the problem of fuzzy filter design is investigated for a class of nonlinear networked systems on the basis of the interval type-2 (IT2) fuzzy set theory. In the design process, two vital factors, intermittent data packet dropouts and quantization, are taken into consideration. The parameter uncertainties are handled effectively by the IT2 membership functions determined by lower and upper membership functions and relative weighting functions. A novel fuzzy filter is designed to guarantee the error system to be stochastically stable with H∞ performance. Moreover, the filter does not need to share the same membership functions and number of fuzzy rules as those of the plant. Finally, illustrative examples are provided to illustrate the effectiveness of the method proposed in this paper.

Control of Nonlinear Networked Systems With Packet Dropouts: Interval Type-2 Fuzzy Model-Based Approach.

In this paper, the problem of fuzzy control for nonlinear networked control systems with packet dropouts and parameter uncertainties is studied based on the interval type-2 fuzzy-model-based approach. In the control design, the intermittent data loss existing in the closed-loop system is taken into account. The parameter uncertainties can be represented and captured effectively via the membership functions described by lower and upper membership functions and relative weighting functions. A novel fuzzy state-feedback controller is designed to guarantee the resulting closed-loop system to be stochastically stable with an optimal performance. Furthermore, to make the controller design more flexible, the designed controller does not need to share membership functions and amount of fuzzy rules with the model. Some simulation results are provided to demonstrate the effectiveness of the proposed results.

Fault detection for T-S fuzzy time-delay systems: delta operator and input-output methods.

This paper focuses on the problem of fault detection for Takagi-Sugeno fuzzy systems with time-varying delays via delta operator approach. By designing a filter to generate a residual signal, the fault detection problem addressed in this paper can be converted into a filtering problem. The time-varying delay is approximated by the two-term approximation method. Fuzzy augmented fault detection system is constructed in δ -domain, and a threshold function is given. By applying the scaled small gain theorem and choosing a Lyapunov-Krasovskii functional in δ -domain, a sufficient condition of asymptotic stability with a prescribed H∞ disturbance attenuation level is derived for the proposed fault detection system. Then, a solvability condition for the designed fault detection filter is established, with which the desired filter can be obtained by solving a convex optimization problem. Finally, an example is given to demonstrate the feasibility and effectiveness of the proposed method.

[Effects of TGF beta 1 on the cell cycle of irradiated human lung fibroblasts and its signal transduction mechanism].

AIM: To investigate the effects of TGF beta 1 on the proliferative activity and cell cycle of normal and gamma ray-irradiated human lung fibroblasts (HLFs). METHODS: HLFs were cultured and irradiated with 3Gy gamma rays and then stimulated by TGF beta 1 at 0.01, 0.1, 1 and 10 microg/L. The proliferative activity and cell cycle were detected by MTT colorimetry and FACS. Furthermore, the expressions of signal proteins Smad3/4 in HLFs were observed by immunohistochemical staining and FACS. RESULTS: TGF beta 1 of 10 microg/L could promote the proliferation of HLFs, with the number of cells in S phase increased. It also could enhance the expression of Smad3 protein and promote the nuclear translocation of Smad4 protein. CONCLUSION: A given dose of TGF beta 1 can promote the proliferation of gamma rays-irradiated HLFs by regulating their cell cycle in which the activation of Smad pathway may play a role.