Mechanistic study of lipid metabolism disorders in diabetic kidney disease treated with GLQMP based on network pharmacology,molecular docking and in vitro experiments

Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.

Exploring the molecular mechanism of Suoquan pill in the treatment of diabetic kidney disease based on network pharmacology,molecular docking,in vitro experiment

Background:Diabetic kidney disease(DKD)is a microvascular complication of diabetes mellitus and is the main cause of end-stage renal failure.Suoquan pills(SQP)has a variety of pharmacological activities and multiple therapeutic effects,and it is used clinically as a basic formula for the treatment of DKD.Methods:Public databases were used to identify SQP compounds and the potential targets of SQP and DKD.A drug-component-therapeutic target network was constructed.Protein-protein interaction network analysis,Gene Ontology functional analysis,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyse the potential molecular mechanisms of SQP based on common targets of drugs and diseases.Molecular docking simulations were conducted to confirm the binding abity of the core compounds to key targets.The efficacy and predicted molecular mechanisms of SQP were validated using cell counting kit-8 assay,flow cytometry,and western blotting with HK-2 cells as a model.Results:Network pharmacology analysis showed that 26 compounds and 207 potential targets of SQP were involved in the treatment of DKD;boldine,denudatin B,pinocembrin,kaempferoid,and quercetin were considered core compounds,and epidermal growth factor receptor(EGFR)and proto-oncogene,non-receptor tyrosine kinase(SRC)were considered key targets.Gene Ontology enrichment analysis indicated that protein phosphorylation and negative regulation of apoptotic processes are important biological processes in the treatment of DKD by SQP.Molecular docking confirmed the excellent binding abilities of boldine,denudatin B,kaempferide,and quercetin to EGFR and SRC.The results of in vitro experiments showed that treatment with an ethanolic extract of SQP significantly protected HK-2 cells from high glucose-induced cell damage.In addition,the SQP ethanol extract inhibited the phosphorylation of EGFR and SRC,suppressed the apoptosis rate,and regulated apoptosis-related proteins in HK-2 cells under high glucose stress.Conclusion:This study systematically and intuitively illustrated the possible pharmacological mechanisms of SQP against DKD through multiple components,targets,and signalling pathways,especially the inhibition of EGFR and SRC phosphorylation and apoptosis.

Strain compensated type Ⅱ superlattices grown by molecular beam epitaxy

We investigate a strain compensation method for the growth of complex interband cascade laser structures. For thick In As/Al Sb superlattice clad layers, the sublayer thicknesses were adjusted so that the tensile strain energy in the In As sublayer was equal to the compressive strain energy in the Al Sb sublayer. For the four-constituent active region, as the compressive strain in the Ga0.65In0.35Sb alloy layer was large, a tensile strain was incorporated in the chirped In As/Al Sb superlattice region for strain compensation to the Ga0.65In0.35Sb alloy. A laser structure of thickness 6 μm was grown on the Ga Sb substrate by molecular beam epitaxy. The wafer exhibited good surface morphology and high crystalline quality.

Flat Top Optical Frequency Combs Based on a Single-Core Quantum Cascade Laser at Wavelength of~8.7μm

We present optical frequency combs with a spectral emission of 48 cm-1and an output power of 420 m W based on a single-core quantum cascade laser at λ ~ 8.7μm. A flat top spectrum sustains up to 130 comb modes delivering ~ 3.2 m W of optical power per mode, making it a valuable tool for dual comb spectroscopy. The homogeneous gain medium, relying on a slightly diagonal bound-to-continuum structure, promises to provide a broad and stable gain for comb operating. Remarkably, the dispersion of this device is measured within 300 fs2/mm to ensure stable comb operation over 90% of the total current range. The comb is observed with a narrow beatnote linewidth around 2 k Hz and has weak dependence on the applied current for stable comb operation.

Tunable characteristic of phase-locked quantum cascade laser arrays

A multimode interference(MMI)structure is designed to simplify the fabrication of quantum cascade laser(QCL)phase-locked arrays.The MMI geometry is optimized with a sufficient output channel distance to accommodate conventional photolithography and wet etching process by which power amplifier array is fabricated without using the complicated two-step etching-regrowth or dry etching technique.The far-field pattern with periodically modulated peaks reveals that the beams from the arrays are phase-locked.Furthermore,the frequency tuning performance of the MMI-based phase-locked arrays is studied using the Littrow-configuration external cavity structure.A wavelength tuning range of more than 60 cm^(−1) is demonstrated,which will eventually realize the high power,frequency tunable,large-scale phase-locked arrays,and their application in spectroscopy.

Broad gain,continuous-wave operation of InP-based quantum cascade laser atλ~11.8μm

We demonstrate a broad gain,continuous-wave(CW)operation InP-based quantum cascade laser(QCL)emitting at 11.8μm with a modified dual-upper-state(DAU)and diagonal transition active region design.A 3 mm cavity length,16.5μm average ridge wide QCL with high-reflection(HR)coatings demonstrates a maximum peak power of 1.07 W at 283 K and CW output power of 60 m W at 293 K.The device also shows a broad and dual-frequency lasing spectrum in pulsed mode and a maximum average power of 258.6 mW at 283 K.Moreover,the full width at half maximum(FWHM)of the electroluminescent spectrum measured at subthreshold current is 2.37μm,which indicates a broad gain spectrum of the materials.The tuning range of 1.38μm is obtained by a grating-coupled external cavity(EC)Littrow configuration,which is beneficial for gas detection.

Beam steering characteristics in high-power quantum-cascade lasers emitting at∼4.6µm

A beam steering effect of high-power quantum cascade(QC) lasers emitting at 4.6 μm was investigated. The continuous wave(CW) output power of an uncoated, 6-mm-long, 7.5-μm-wide buried-heterostructure QC laser at 25℃ was as high as 854.2 m W. The maximum beam steering angle was offset by ±14.2° from the facet normal(0°) in pulsed mode. The phenomenon was judged explicitly by combining the diffraction limit theory and Fourier transform of the spectra. It was also verified by finite element method software simulation and the calculation of two-dimensional(2 D)effective-index model. The observed steering is consistent with a theory for coherence between the two lowest order lateral modes. Therefore, we have established an intrinsic linkage between the spectral instabilities and the beam steering by using the Fourier transform of the spectra, and further presented an extremely valid method to judge the beam steering. The content of this method includes both three equidistant peak positions in the Fourier transform of the spectra and the beam quality located between once the diffraction limit(DL) and twice the DL.

Chirped coupled ridge waveguide quantum cascade laser arrays with stable single-lobe far-field patterns

Power scaling in a broad area quantum cascade laser(QCL) tends to deteriorate beam quality with the emission of a multiple-lobe far-field pattern. In this paper, we demonstrate a coupled ridge waveguide QCL array consisting of five elements with chirped geometry. In-phase mode operation is secured by managing supermode loss with properly designed geometries of ridges. A single-lobe lateral far-field with a near diffraction limited beam pattern was obtained in the whole current dynamic range. The devices were fabricated with the wet and dry etching method. The regrowth technique of the In P:Fe insulation layer and In P:Si waveguide layer was employed.Such a structure has the potential to optimize the beam quality of the recently reported high-power broad-area QCL with a reduced cascade number.

Stable single-mode operation of a distributed feedback quantum cascade laser integrated with a distributed Bragg reflector

We report an index-coupled distributed feedback quantum cascade laser by employing an equivalent phase shift(EPS) of quarter-wave integrated with a distributed Bragg reflector(DBR) at λ~5.03 μm. The EPS is fabricated through extending one sampling period by 50% in the center of a sampled Bragg grating. The key EPS and DBR pattern are fabricated by conventional holographic exposure combined with the optical photolithography technology, which leads to improved flexibility, repeatability, and cost-effectiveness. Stable single-mode emission can be obtained by changing the injection current or heat sink temperature even under the condition of large driving pulse width.

Multi-wavelength sampled Bragg grating quantum cascade laser arrays

A multi-wavelength sampled Bragg grating(SBG) quantum cascade laser array operating between 7.32 and7.85 μm is reported. The sampling grating structure, which can be analyzed as a conventional grating multiplied by a sampling function, is fabricated by holographic exposure combined with optical photolithography. The sampling grating period was varied from 8 to 32 μm, and different sampling order(-1 st,-2 nd, and-3 rd order)modes were achieved. We propose that higher-order modes with optimized duty cycles can be used to take full advantage of the gain curve and improve the wavelength coverage of the SBG array, which will be beneficial to many applications.