Heyingwuzi formulation alleviates diabetic retinopathy by promoting mitophagy via the HIF-1α/BNIP3/NIX axis

BACKGROUND Diabetic retinopathy(DR)is the primary cause of visual problems in patients with diabetes.The Heyingwuzi formulation(HYWZF)is effective against DR.AIM To determine the HYWZF prevention mechanisms,especially those underlying mitophagy.METHODS Human retinal capillary endothelial cells(HRCECs)were treated with high glucose(hg),HYWZF serum,PX-478,or Mdivi-1 in vitro.Then,cell counting kit-8,transwell,and tube formation assays were used to evaluate HRCEC proliferation,invasion,and tube formation,respectively.Transmission electron microscopy was used to assess mitochondrial morphology,and Western blotting was used to determine the protein levels.Flow cytometry was used to assess cell apoptosis,reactive oxygen species(ROS)production,and mitochondrial membrane potential.Moreover,C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks.Blood glucose levels and body weight were monitored continuously.Changes in retinal characteristics were evaluated using hematoxylin and eosin,tar violet,and periodic acid-Schiff staining.Protein levels in retinal tissues were determined via Western blotting,immunohistochemistry,and immunostaining.RESULTS HYWZF inhibited excessive ROS production,apoptosis,tube formation,and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro.It increased the mRNA expression levels of BCL2-interacting protein 3(BNIP3),FUN14 domain-containing 1,BNIP3-like(BNIP3L,also known as NIX),PARKIN,PTEN-induced kinase 1,and hypoxia-inducible factor(HIF)-1α.Moreover,it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio.However,PX-478 and Mdivi-1 reversed these effects.Additionally,PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy.HYWZF intervention improved the symptoms of diabetes,tissue damage,number of acellular capillaries,and oxidative stress in vivo.Furthermore,in vivo experiments confirmed the results of in vitro experiments.CONCLUSION HYWZF alleviated DR and associated damage by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.

Glycemic Responses of Food Formulations Based on White Rice and White Bean

The management of diabetes mellitus is based on lifestyle and dietary measures suggesting the consumption of foods with a low glycemic index. The present study was conducted in order to propose food formulas based on white rice and white beans resulting in a lower glycemic response. For this, food formulations based on these foods were first made, in particular the formulation [75% white rice + 25% white beans] and the formulation [50% rice + 50% white beans]. Then, the biochemical composition of white rice, white bean and these two formulations was determined by the usual methods. Finally, their glycemic responses over 120 minutes were studied by the FAO/ WHO 1998 method. The results showed that white rice [100% white rice] had the highest carbohydrate content (54.61%) followed respectively by the formulation [75% white rice + 25% white bean] (45.69%), the white bean [100% white bean] (29.1%) and the formulation [50% white rice + 50% white bean] (26.16%). In terms of glycemic responses, the formulation [50% white rice + 50% white beans] presented the best evolution with a lower peak (6.041 mmol/L) observed at T45min and a lower postprandial glycemia (4.872 mmol/ L) at T120min. An increase in the proportion of beans is therefore recommended as it may suggest a beneficial metabolic effect.

Effectiveness of an amino acid beverage formulation in diarrheapredominant irritable bowel syndrome:A pragmatic real-world study

BACKGROUND Amino-acid based medical foods have shown promise in alleviating symptoms of drug induced gastrointestinal side effects;particularly,diarrhea-predominant symptoms.Irritable bowel syndrome(IBS)is a gastrointestinal disorder that affects up to 9% of people globally,with diarrhea predominant IBS(IBS-D)being the most prevalent subtype.Further trials are needed to explore potential added benefits when integrated into standard care for IBS-D.AIM To assess the effectiveness of an amino acid-based medical food as an adjunct to standard of care for adults with IBS-D.METHODS This is a pragmatic,real world,open label,single arm study comparing a 2-week baseline assessment to a 2-week intervention period.One hundred adults,aged 18 to 65 years,with IBS-D,according to Rome IV criteria,were enrolled after completing a 2-week baseline assessment period and received a 2-week supply of an amino acid based medical food which was consumed at home twice daily on top of their standard of care.The primary outcome was an assessment of tolerability after 2-weeks of consumption,while secondary outcomes included changes in stool consistency(Bristol Stool Form Scale),severity of abdominal pain&discomfort,symptoms of urgency,Global Improvement Survey(GIS),and the IBS severity scoring system(IBS-SSS).RESULTS The test product was well-tolerated as each participant successfully completed the full 14-day trial,and there were no instances of dropouts or discontinuation of the study product reported.Forty percent of participants achieved a 50% or more reduction in the number of days with type 6-7 bowel movements(IBS-D stool consistency responders).Fifty-three percent of participants achieved a clinically meaningful reduction of 30% in mean weekly pain scores,and 55%experienced the same for mean weekly discomfort scores(IBS-D pain and discomfort responders).Participants experienced a mean-109.4(95% confidence interval:-130.1,-88.8)point reduction on the IBS-SSS and 52% experienced a minimally clinically important difference of>95 points.An IBS-SSS category shift from severe to moderate or mild occurred in 69% of participants.For functional symptoms,76% of participants reported symptom relief on the GIS.CONCLUSION The amino acid-based medical food was well-tolerated,when added to the standard of care,and demonstrated improvements in both overall IBS symptom severity and IBS-D symptoms within just 2 wk.

Predicting liposome formulations by the integrated machine learning and molecular modeling approaches

Liposome is one of the most widely used carriers for drug delivery because of the great biocompatibility and biodegradability.Due to the complex formulation components and preparation process,formulation screening mostly relies on trial-and-error process with low efficiency.Here liposome formulation prediction models have been built by machine learning(ML)approaches.The important parameters of liposomes,including size,polydispersity index(PDI),zeta potential and encapsulation,are predicted individually by optimal ML algorithm,while the formulation features are also ranked to provide important guidance for formulation design.The analysis of key parameter reveals that drug molecules with logS[-3,-6],molecular complexity[500,1000]and XLogP3(≥2)are priority for preparing liposome with higher encapsulation.In addition,naproxen(NAP)and palmatine HCl(PAL)represented the insoluble and water-soluble molecules are prepared as liposome formulations to validate prediction ability.The consistency between predicted and experimental value verifies the satisfied accuracy of ML models.As the drug properties are critical for liposome particles,the molecular interactions and dynamics of NAP and PAL liposome are further investigated by coarse-grained molecular dynamics simulations.The modeling structure reveals that NAP molecules could distribute into lipid layer,while most PAL molecules aggregate in the inner aqueous phase of liposome.The completely different physical state of NAP and PAL confirms the importance of drug properties for liposome formulations.In summary,the general prediction models are built to predict liposome formulations,and the impacts of key factors are analyzed by combing ML with molecular modeling.The availability and rationality of these intelligent prediction systems have been proved in this study,which could be applied for liposome formulation development in the future.

Effect of Synthetic Conditions and Thickener Formulation on the Rheological and Tribological Properties of Polypropylene Grease

Polypropylene(PP)grease holds great potential for special industrial applications.In this study,synthetic conditions,thickener content,and the ratio of two different molecular weight PPs were investigated systematically using a rheometer,scanning electron microscope,X-ray diffraction,Fourier transform infrared spectrometer,oscillating tribometer,and 3D surface profiler measurements.The results showed that suitable synthetic conditions are two quenching cycles,and the synthetic temperature and time is 240℃for 12 h.The rheological analysis showed that thickener content and different proportions of the two PP molecular weights have a significant influence on the rheological properties of PP grease.High molecular weight PP(H-PP)has a stronger thickening ability than low molecular weight PP(L-PP).The higher the amount of H-PP in the fixed thickener content or the higher the thickener content with a specific proportion,the higher the viscoelasticity of PP grease.The tribological performance is related to the rheological properties.The proportion of two different molecular weight PPs in the thickener content should be appropriate;excessive H-PP content leads to lubrication failure.

Eigen value analysis of composite hollow shafts using modified EMBT formulation considering the shear deformation along the thickness direction

Composite hollow shafts are used in power transmission applications due to their high specific stiffness and high specific strength.The dynamic characteristics of these shafts are important for transmission applications.Dynamic modelling of these shafts is generally carried out using Equivalent Modulus Beam Theory(EMBT)and Layerwise Beam Theory(LBT)formulations.The EMBT formulation is modified by considering stacking sequence,shear normal coupling,bending twisting coupling and bending stretching coupling.It is observed that modified EMBT formulation is underestimating the shafts stiffness at lower length/mean diameter(l/dm)ratios.In the present work,a new formulation is developed by adding shear deformation along the thickness direction to the existing modified EMBT formulation.The variation of shear deformation along the thickness direction is found using different shear deformation theories,i.e.,first-order shear deformation theory(FSDBT),parabolic shear deformation theory(PSDBT),trigonometric shear deformation theory(TSDBT),and hyperbolic shear deformation theory(HSDBT).The analysis is performed at l/d_(m) ratios of 5,10,15,20,25,30,35,and 40 for carbon/epoxy composites,E-glass/epoxy composites,and boron/epoxy composite shafts.The results show that new formulation has improved the bending natural frequency of the composite shafts for l/d_(m)<15 in comparison with modified EMBT.The effect of new formulation is more significant for the second and third bending modes of natural frequencies.

Formulation and Antioxidant Activity Evaluation of Theaflavin Effervescent Tablet

Theaflavins(TFs),as the major polyphenolic components of fermented tea,possess beneficial effects on human health.In this study,the effervescent tablets based on theaflavins were developed.The optimal formulation of TF effervescent tablets was obtained by response surface methodology with the Box-Behnken design.Then,the physiochemical properties were evaluated,including hardness,friability,effervescent time and pH of the solution.At last,the antioxidant ability of TF effervescent tablets was studied through DPPH and ABTS radical scavenging assay.According to the results,the optimal formulation of the tablets contained TF powder 9.09%,disintegrating agent 43.80%(the weight ratio of citric acid and sodium bicarbonate was 1:1),aspartame 1.86%,PEG-6003%,and mannitol in balance.With the wet granulation method,the TF effervescent tablets displayed suitable hardness,fast disintegration time,good color,pleasant taste and high antioxidant activity.This study demonstrated that the TF effervescent tablets could be a valuable product for the supplement market and contribute to promoting practical application of TFs.

Water-Based Environmentally Friendly Pesticide Formulations Based on Cyclodextrin/Pesticide Loading System

Difenoconazole(DIF)is a representative variety of broad-spectrum triazole fungicides and liposoluble pesticides.However,the water solubility of DIF is so poor that its application is limited in plant protection.In addition,the conventional formulations of DIF always contain abundant organic solvents,which may cause pollution of the environment.In this study,two DIF/cyclodextrins(CDs)inclusion complexes(ICs)were successfully prepared,which were DIF/β-CD IC and DIF/hydroxypropyl-β-CD IC(DIF/HP-β-CD IC).The effect of cyclodextrins on the water solubility and the antifungal effect of liposoluble DIF pesticide were investigated.According to the phase solubility test,the molar ratio and apparent stability constant of ICs were obtained.Fourier transform infrared spectroscopy,thermal gravity analysis,X-ray diffraction and scanning electron microscopy were used systematically to characterize the formation and characteristics of ICs.The results noted that DIF successfully entered the cavities of two CDs.In addition,the antifungal effect test proved the better performance of DIF/HP-β-CD IC,which exceeded that of DIF emulsifiable concentrate.Therefore,our study provides informative direction for the intelligent use of liposoluble pesticides with cyclodextrins to develop water-based environmentally friendly formulations.

Entropy Formulation for Triply Nonlinear Degenerate Elliptic-Parabolic-Hyperbolic Equation with Zero-Flux Boundary Condition

In this note, we investigated existence and uniqueness of entropy solution for triply nonlinear degenerate parabolic problem with zero-flux boundary condition. Accordingly to the case of doubly nonlinear degenerate parabolic hyperbolic equation, we propose a generalization of entropy formulation and prove existence and uniqueness result without any structure condition.

Optimization of the Formulation Process of Glucosamine Chondroitin Sulfate Tablets

[Objectives]This study was conducted to optimize the Formulation Process of glucosamine chondroitin sulfate tablets. [Methods] The orthogonal design with three levels was carried out with microcrystalline cellulose, calcium hydrophosphate and cross-linked polyvinylpyrrolidone as three factors to optimize the preparation process. [Results] When microcrystalline cellulose 200 mg/tablet, calcium hydrophosphate 150 mg/tablet, and cross-linked polyvinylpyrrolidone 80 mg/tablet were added, the angle of repose could meet the requirements of tablet pressing, and the dissolution could reach more than 95% in 30 min. The results of the orthogonal test showed that the dissolution effect of self-made tablets was faster than that of commercial products. [Conclusions] The glucosamine hydrochloride chondroitin sulfate tablets prepared by this prescription have better quality.

中国法庭互动话语formulation现象研究

本文专门研究法庭互动话语formulation现象,旨在揭示法庭互动话语这种具有特殊规则制约的机构话语的formulation的特征,并对机构话语的研究和司法人员提供启示。具体内容是:(1)法庭话语formulation的类型;(2)法庭话语formulation的功能;(3)法庭互动话语formulation行为的特征;(4)法庭话语formulation与互动结构;(5)法庭互动话语formulation与角色关系。

用油墨配方软件Ink Formulation5.0调配专色墨实例

经验配色法常常受到配色者生理、心理因素及其它客观条件的影响,产品质量难以保持稳定,油墨浪费较大,剩余油墨利用率低.另外,依靠经验和感觉配色,只能定性,无法定量,技术的传播与交流比较困难. 电脑配色系统是集测色仪、计算机及配色软件系统于一体的现代化设备.计算机配色的基本原理是将生产上配色所用油墨的颜色数据,预先储存在电脑中,应用其计算出用这些油墨配得与原稿色相同颜色的混合比例,从而达到实现配方的目的.常用的工具有:打样机或印刷适性仪(图1)、电子天平(图2)、分光光度仪(图3)、标准光源(图4)、配色软件(图5)等.

Effect Comparison of different formulation of Dang-Gui-Bu-Xu-Tang on myelosuppression mouse

Objective:To compare effect of different formulation of Dang-Gui-Bu-Xu-Tang（DCBXT） on myelosuppression mouse.Methods:HPLC was used to measure active ingredients of two DGBXT formulations,Hemopoesic function of bone marrow was measured by hemopoietic progenitor cell culture and peipheral blood count.And hemopoietic factors in bone marrow were tested by ELISA.Results:The content level of astragaloside A in granule formulation was higher than that in decoction and the content ratio of active ingredient was close to 5:1.Two DGBXD formulations could significantly improve amount of peripheral blood cells,and bone marrow cells of bone marrow suppression mice（P【0.05）.DGBXD granule formulation significantly increased the colony quantity of all progenitor cell lines and amount of G2/M and S phase cells（P【0.05）. It also significantly decreased amount of G0/G1 phase cells in the bone marrow and was more effective（P【0.05）.Conclusions:DGBXT decoction and the granule formulation all can improve the hematopoietic function of bone marrow suppression mouse.They can improve quantities of peripheral blood and nucleated bone marrow cells,and yield of the hematopoietic stem/progenitor cells in vitro colony;balance the expression of cytokine（EPO,TPO and GM-GSF） in bone marrow microenvirement.They can also facilitate hematopoietic stem/progenitor cells to enter the cell cycle.And the effect of granule formulation is more satisfactory.

Nonlinear formulation for flexible multibody system with large deformation

In this paper, nonlinear modeling for flexible multibody system with large deformation is investigated. Absolute nodal coordinates are employed to describe the displacement, and variational motion equations of a flexible body are derived on the basis of the geometric nonlinear theory, in which both the shear strain and the transverse normal strain are taken into account. By separating the inner and the boundary nodal coordinates, the motion equations of a flexible multibody system are assembled. The advantage of such formulation is that the constraint equations and the forward recursive equations become linear because the absolute nodal coordinates are used. A spatial double pendulum connected to the ground with a spherical joint is simulated to investigate the dynamic performance of flexible beams with large deformation. Finally, the resultant constant total energy validates the present formulation.

An exact nonlinear hybrid-coordinate formulation for flexible multibody systems

The previous low-order approximate nonlinear formulations succeeded in capturing the stiffening terms, but failed in simulation of mechanical systems with large deformation due to the neglect of the high-order deformation terms. In this paper, a new hybrid-coordinate formulation is proposed, which is suitable for flexible multibody systems with large deformation. On the basis of exact strain- displacement relation, equations of motion for flexible multi-body system are derived by using virtual work principle. A matrix separation method is put forward to improve the efficiency of the calculation. Agreement of the present results with those obtained by absolute nodal coordinate formulation （ANCF） verifies the correctness of the proposed formulation. Furthermore, the present results are compared with those obtained by use of the linear model and the low-order approximate nonlinear model to show the suitability of the proposed models.

Fermentation, formulation and evaluation of PGPR Bacillus subtilis isolate as a bioagent for reducing occurrence of peanut soil-borne diseases

Four isolates of Bacillus subtilis coded,B4,B7,B8 and B10 were examined as biocontrol agents for their abilities and antagonistic effect on the in vitro growth of certain phytopathogenic fungi of peanut,Rhizoctonia solani and Sclerotium rolfsii.Bacillus subtilis isolate B4(GenBank accession no.EF150884)was the highly effective one for inhibiting the fungal mycelial growth.Batch fermentation of B.subtilis isolate B4 was carried out and the maximum biomass achieved was 4.53 g L-1 at 11 h.Bacillus subtilis isolate B4 was formulated and evaluated as a biofungicide to reduce peanut soil-borne diseases under greenhouse and field conditions at the side of Rizolex-T(fungicide)as standard.Treatments by formulated plant growth-promoting rhizobacteria(PGPR)B.subtilis B4 and Rizolex-T in a soil infested with R.solani,S.rolfsii and mixture of them were more effective in decreasing percentage of damping-off,root and pod rot disease incidence(%)in greenhouse and open field environment during the two seasons 2015 and 2016.Treatments by PGPR gave highly dry weight and number of healthy pods compared to control of fungi treatment which was nearby to dry weights of healthy pods achieved by treatments by Rizolex-T in a soil infested with S.rolfsii,R.solani and mixture of them.Formulated PGPR B.subtilis B4 gave higher increasing of yield percentage than treatment by Rizolex-T in the two evaluated seasons 2015 and 2016.It can conclude that the produced bioforumlated agent was more efficient as fungicide when compared with the other chemical synthesized fungicides,safe for human and the environment and economy.

A New Elasticity and Finite Element Formulation for Different Young's Modulus When Tension and Compression Loadings

This paper presents a new elasticity and finite element formulation for different Young's modulus when tension and compression loadings in anisotropy media. The case studies, such as anisotropy and isotropy, were investigated. A numerical example was shown to find out the changes of neutral axis at the pure bending beams.

Complex formulations, simple techniques: Can 3D printing technology be the Midas touch in pharmaceutical industry?

3 D printing is a method of rapid prototyping and manufacturing in which materials are deposited onto one another in layers to produce a three-dimensional object. Although 3 D printing was developed in the 1980 s and the technology has found widespread industrial applications for production from automotive parts to machine tools,its application in pharmaceutical area is still limited. However,the potential of 3 D printing in the pharmaceutical industry is now being recognized. The ability of 3 D printing to produce medications to exact specifications tailored to the needs of individual patients has indicated the possibility of developing personalized medicines. The technology allows dosage forms to be precisely printed in various shapes,sizes and textures that are difficult to produce using traditional techniques. However,there are various challenges associated with the proper application of3 D printing in the pharmaceutical sector which should be overcome to exploit the scope of this technology. In this review,an overview is provided on the various 3 D printing technologies used in fabrication of complex dosage forms along with their feasibility and limitations.

NUMERICAL SOLUTION OF VISCOUS FLOW PAST A SOLID SPHERE WITH THE CONTROL VOLUME FORMULATION

The control volume formulation with the QUICK finite difference scheme is used to solveincompressible liquid flow past a solid sphere in terms of stream function and vorticity.Several tech-nical points are addressed on improving the accuracy and efficiency of numerical simulation of similarproblems of fluid flow.In particular,the importance of suitable specification of the distortion func-tion to enforcing the far field boundarv conditions is emphasized.

A REDUCED MFE FORMULATION BASED ON POD FOR THE NON-STATIONARY CONDUCTION-CONVECTION PROBLEMS

In this article, a reduced mixed finite element （MFE） formulation based on proper orthogonal decomposition （POD） for the non-stationary conduction-convection problems is presented. Also the error estimates between the reduced MFE solutions based on POD and usual MFE solutions are derived. It is shown by numerical examples that the results of numerical computation are consistent with theoretical conclusions. Moreover, it is shown that the reduced MFE formulation based on POD is feasible and efficient in finding numerical solutions for the non-stationary conduction-convection problems.