Compound 3k治疗骨关节炎:调控氧化应激通路改善软骨细胞糖酵解的作用机制

背景:骨关节炎现已被认为是一种代谢性疾病,既往研究表明糖酵解在骨关节炎的发生发展中起重要作用。Compound 3k作为一种新型糖酵解小分子抑制剂,具有抗炎及抗肿瘤等功效,因此可靶向糖酵解,有望为骨关节炎治疗提供新的思路。目的:基于缺氧诱导因子1α/活性氧的氧化应激通路探究Compound 3k在糖酵解过度活跃所导致的骨关节炎中的作用机制。方法:取对数生长期的ATDC5成软骨细胞,用10 ng/mL白细胞介素1β作用24 h诱导骨关节炎体外细胞模型,以CCK-8法检测不同浓度(0.25,0.5,1,2.5,5,10,15μmol/L)Compound 3k的细胞毒性,选出合适浓度进行后续实验。将软骨细胞随机分为对照组、模型组、治疗组,模型组以10 ng/mL的白细胞介素1β诱导,治疗组以Compound 3k预刺激2 h后与白细胞介素1β共培养,用CCK-8法检测各组细胞增殖情况;用ELISA试剂盒检测各组细胞炎症水平;用试剂盒检测各组细胞活性氧、细胞外乳酸脱氢酶及葡萄糖含量;qRT-PCR及Western blot检测相关炎症因子白细胞介素6、肿瘤坏死因子α及糖酵解相关基因葡萄糖转运蛋白1、甘油醛3-磷酸脱氢酶、单羧酸转运蛋白1和缺氧诱导因子1α的表达水平。结果与结论:①与对照组相比,模型组细胞增殖活性下降、糖酵解水平活跃,表现为细胞外乳酸脱氢酶含量增加(P<0.001),葡萄糖含量减少(P<0.001),相关炎症因子白细胞介素6(P<0.0001)及肿瘤坏死因子α(P<0.001),糖酵解相关基因葡萄糖转运蛋白1(P<0.001)、甘油醛3-磷酸脱氢酶(P<0.001)、单羧酸转运蛋白1(P<0.001)及缺氧诱导因子1α(P<0.001)的表达水平均上调,并伴随氧化应激,活性氧过量产生。②与模型组相比,Compound 3k的治疗有效提高细胞增殖活性,抑制过度活跃的糖酵解水平的同时,抑制了骨关节炎软骨细胞炎症(P<0.001)及糖酵解相关基因的表达(P<0.001),且抑制氧化应激,缺氧诱导因子1α的表达水平下调(P<0.0001),活性氧水平下降。③上述结果证实,Compound 3k抑制了白细胞介素1β诱导的软骨细胞炎症,其机制可能与糖酵解及缺氧诱导因子1α/活性氧介导的氧化应激有关。

Harnessing multi-omics approaches to elucidate the role of Chinese herbal compounds in chemotherapy-induced gastrointestinal damage

In this editorial,we discuss the findings reported by Wang et al in the latest issue of the World Journal of Gastrointestinal Oncology.Various research methodologies,including microbiome analysis,assert that the Tzu-Chi Cancer-Antagonizing and Life-Protecting II Decoction of Chinese herbal compounds mitigates inflammatory responses by inhibiting the NF-κB signaling pathway.This action helps maintain the dynamic equilibrium of the intestinal microecology and lessens chemotherapy-induced gastrointestinal damage.The efficacy of these compounds is intimately linked to the composition of intestinal microbes.These compounds regulate intestinal microecology by virtue of their specific compatibility and effectiveness,thereby enhancing the overall therapeutic outcomes of cancer chemotherapy.Nonetheless,the exact mechanisms underlying these effects warrant further investigation.Multi-omics technologies offer a systematic approach to elucidate the mechanisms and effectiveness of Chinese herbal compounds in vivo.This manuscript reviews the application of multi-omics technologies to Chinese herbal compounds and explores their potential role in modulating the gastrointestinal microenvironment following cancer chemotherapy,thus providing a theoretical foundation for their continued use in adjunct cancer treatment.

Novel Method for Preparation of Polypropylene Blends with High Melt Strength by Reactive Compounding

Ultrafine full-vulcanized polybutadiene rubber（UFBR） with particle sizes of ca.50―100 nm were used for modifying mechanical and processing performances of polypropylene（PP） with PP-g-maleic anhydride（PP-g-MA） as a compatibilizer for enhancing the interfacial adhesion between the two components.The morphology,dynamical rheology response and mechanical properties of the blends were characterized by means of SEM,rheometer and tensile test,respectively.The results show that the ternary PP/UFBR blends compatibilized with PP-g-MA possess rheological behaviors like highly branched PP,while no obvious strain hardening is observed in its control binary PP/UFBR blends,a low level of PP-g-MA in PP/UFBR blends can even endow the material with rheological characteristics of high melt strength materials like highly branched PP.The enhancement interfacial interaction between the UFBR particles and PP matrix accounting for the rheological behavior of compatibilized blends and effectiveness of PP-g-MA were proposed and proved.

Comparative evaluation of commercial Douchi by different molds:biogenic amines,non-volatile and volatile compounds

To provide new insights into the development and utilization of Douchi artificial starters,three common strains(Aspergillus oryzae,Mucor racemosus,and Rhizopus oligosporus)were used to study their influence on the fermentation of Douchi.The results showed that the biogenic amine contents of the three types of Douchi were all within the safe range and far lower than those of traditional fermented Douchi.Aspergillus-type Douchi produced more free amino acids than the other two types of Douchi,and its umami taste was more prominent in sensory evaluation(P<0.01),while Mucor-type and Rhizopus-type Douchi produced more esters and pyrazines,making the aroma,sauce,and Douchi flavor more abundant.According to the Pearson and PLS analyses results,sweetness was significantly negatively correlated with phenylalanine,cysteine,and acetic acid(P<0.05),bitterness was significantly negatively correlated with malic acid(P<0.05),the sour taste was significantly positively correlated with citric acid and most free amino acids(P<0.05),while astringency was significantly negatively correlated with glucose(P<0.001).Thirteen volatile compounds such as furfuryl alcohol,phenethyl alcohol,and benzaldehyde caused the flavor difference of three types of Douchi.This study provides theoretical basis for the selection of starting strains for commercial Douchi production.

Compounding Pattern of REE， Clay and Humic Acid in the Weathering Crust of Granites

An anomalous phase containing clays and humic acid was found while extraction humic acid from samples of weathering crust of REE-bearing granites by using 0.1 mol/L NaOH solution.Studied by chemical separation experiments,column chromatography,ion-exchange chromatography,infrared spectrum.fluorescence spectrum,polarimicroscopic testing and elemental determination by ultraviolet-visible spectrometer and atomic absorption spectrometer.it was proved to be a compound of humic acid and clays which are connected in the form of bridge by heteronuclearpolynuclear complexing ions formed by cations of RE￣(5+),Al￣(3+).Fe￣(3+) etc.The compounding pattern was further proved by the experiment for compounding humic acid,REE and kaolinite.

Effect of different drying methods on the amino acids,α-dicarbonyls and volatile compounds of rape bee pollen

The significant demand for high quality food has motivated us to adopt appropriate processing methods to improve the food nutritional quality and flavors.In this study,the effects of five drying methods,namely,pulsed vacuum drying(PVD),freeze drying(FD),infrared drying(IRD),hot-air drying(HAD)and sun drying(SD)on free amino acids(FAAs),α-dicarbonyl compounds(α-DCs)and volatile compounds(VOCs)in rape bee pollen(RBP)were determined.The results showed that FD significantly released the essential amino acids(EAAs)compared with fresh samples while SD caused the highest loss.Glucosone was the dominantα-DCs in RBP and the highest loss was observed after PVD.Aldehydes were the dominant volatiles of RBP and SD samples contained more new volatile substances(especially aldehydes)than the other four drying methods.Comprehensively,FD and PVD would be potential methods to effectively reduce the quality deterioration of RBP in the drying process.

Optimization Analysis of Correction Tape Box Compounding Cavity Runner Balance Based on Moldflow

Aiming at the problem of runner unbalance in the compounding cavity of the upper and lower cover of the correction tape box, the plastic injection analysis software Moldflow was used to optimize runner balance. First, the 3D modeling software Proe was used to establish the geometric model of the upper and lower cover of the correction tape box, and introduced into the plastic injection analysis software Moldflow. Secondly, the upper and the lower cover of the correction tape box were meshed and the initial gating system was designed in Moldflow. Filling analysis of the initial scheme of the correction tape box combined cavity showed that the runner of the melt was not balanced in the mold cavity. Finally, the runner balance optimization analysis of the cavities was carried out. Through optimization, the time unbalance rate of the melt in the mold cavity decreased from 28.6% to 0.7%, the pressure unbalance rate decreased from 42.0% to 4.2%, and the pressure distribution in the cavity was more uniform in the whole injection process.

Numerical modeling of fracture propagation of supercritical CO_(2)compound fracturing

The exploitation of shale gas is promising due to depletion of the conventional energy and intensification of the greenhouse effect.In this paper,we proposed a heat-fluid-solid coupling damage model of supercritical CO_(2)(SC-CO_(2))compound fracturing which is expected to be an efficient and environmentally friendly way to develop shale gas.The coupling model is solved by the finite element method,and the results are in good agreement with the analytical solutions and fracturing experiments.Based on this model,the fracture propagation characteristics at the two stages of compound fracturing are studied and the influence of pressurization rate,in situ stress,bedding angle,and other factors are considered.The results show that at the SC-CO_(2)fracturing stage,a lower pressurization rate is conducive to formation of the branches around main fractures,while a higher pressurization rate inhibits formation of the branches around main fractures and promotes formation of the main fractures.Both bedding and in situ stress play a dominant role in the fracture propagation.When the in situ stress ratio(δ_(x)/δ_(y))is 1,the presence of bedding can reduce the initiation pressure and failure pressure.Nevertheless,it will cause the fracture to propagate along the bedding direction,reducing the fracture complexity.In rocks without bedding,hydraulic fracturing has the lengthening and widening effects for SC-CO_(2)induced fracture.In shale,fractures induced at the hydraulic fracturing stage are more likely to be dominated by in situ stresses and have a shorter reorientation radius.Therefore,fracture branches propagating along the maximum principal stress direction may be generated around the main fractures induced by SC-CO_(2)at the hydraulic fracturing stage.When the branches converge with the main fractures,fracture zones are easily formed,and thus the fracture complexity and damage area can be significantly increased.The results are instructive for the design and application of SC-CO_(2)compound fracturing.

Significant contributions of the petroleum industry to volatile organic compounds and ozone pollution:Insights from year-long observations in the Yellow River Delta

The petroleum industry is a significant source of anthropogenic volatile organic compounds(VOCs),but up to now,its exact impact on urban VOCs and ozone(O_(3))remains unclear.This study conducted year-long VOC ob-servations in Dongying,China,a petroleum industrial region.The VOCs from the petroleum industry(oil and gas volatilization and petrochemical production)were identified by employing the positive matrix factorization model,and their contribution to O_(3) formation was quantitatively evaluated using an observation-based chemical box model.The observed annual average concentration of VOCs was 68.6±63.5 ppbv,with a maximum daily av-erage of 335.3 ppbv.The petroleum industry accounted for 66.5%of total VOCs,contributing 54.9%from oil and gas evaporation and 11.6%from petrochemical production.Model results indicated that VOCs from the petroleum industry contributed to 31%of net O_(3) production,with 21.3%and 34.2%contributions to HO_(2)+NO and RO_(2)+NO pathways,respectively.The larger impact on the RO_(2) pathway is primarily due to the fact that OH+VOCs ac-count for 86.9%of the primary source of RO_(2).This study highlights the critical role of controlling VOCs from the petroleum industry in urban O_(3) pollution,especially those from previously overlooked low-reactivity alkanes.

Role of methoxy and C_(α)-based substituents in electrochemical oxidation mechanisms and bond cleavage selectivity of β-O-4 lignin model compounds

In order to better understand the specific substituent effects on the electrochemical oxidation process of β-O-4 bond, a series of methoxyphenyl type β-O-4 dimer model compounds with different localized methoxyl groups, including 2-(2-methoxyphenoxy)-1-phenylethanone, 2-(2-methoxyphenoxy)-1-phenylethanol, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanol, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanol have been selected and their electrochemical properties have been studied experimentally by cyclic voltammetry, and FT-IR spectroelectrochemistry. Combining with electrolysis products distribution analysis and density functional theory calculations, oxidation mechanisms of all six model dimers have been explored. In particular, a total effect from substituents of both para-methoxy(on the aryl ring closing to Cα) and Cα-OH on the oxidation mechanisms has been clearly observed, showing a significant selectivity on the Cα-Cβbond cleavage induced by electrochemical oxidations.

Modern approaches for detection of volatile organic compounds in metabolic studies focusing on pathogenic bacteria:Current state of the art

Pathogenic microorganisms produce numerous metabolites,including volatile organic compounds(VOCs).Monitoring these metabolites in biological matrices(e.g.,urine,blood,or breath)can reveal the presence of specific microorganisms,enabling the early diagnosis of infections and the timely implementation of tar-geted therapy.However,complex matrices only contain trace levels of VOCs,and their constituent com-ponents can hinder determination of these compounds.Therefore,modern analytical techniques enabling the non-invasive identification and precise quantification of microbial VOCs are needed.In this paper,we discuss bacterial VOC analysis under in vitro conditions,in animal models and disease diagnosis in humans,including techniques for offline and online analysis in clinical settings.We also consider the advantages and limitations of novel microextraction techniques used to prepare biological samples for VOC analysis,in addition to reviewing current clinical studies on bacterial volatilomes that address inter-species in-teractions,the kinetics of VOC metabolism,and species-and drug-resistance specificity.

Preparation of lactic acid bacteria compound starter cultures based on pasting properties and its improvement of glutinous rice flour and dough

The effects of 5 lactic acid bacteria(LAB)fermentation on the pasting properties of glutinous rice flour were compared,and suitable fermentation strains were selected based on the changes of viscosity,setback value,and breakdown value to prepare LAB compound starter cultures.The results revealed that Latilactobacillus sakei HSD004 and Lacticaseibacillus rhamnosus HSD005 had apparent advantages in increasing the viscosity and reducing the setback and breakdown values of glutinous rice flour.In particular,the compound starter created using the two abovementioned LAB in the ratio of 3:1 had better performance than that using a single LAB in improving the pasting properties and increasing the water and oil absorption capacity of glutinous rice flour.Moreover,the gelatinization enthalpy of the fermented samples increased significantly.For frozen glutinous rice dough stored for 28 days,the viscoelasticity of frozen dough prepared by compound starter was better than that of control dough,and the freezable water content was lower than that of control dough.These results indicate that compound LAB fermentation is a promising technology in the glutinous rice-based food processing industry,which has significance for its application.

Optimization of ultrasonic elastography by coded excitation and transmit-side multi-frequency compounding

To improve the quality of ultrasonic elastography, by taking the advantage of code excitation and frequency compounding, a transmitting-side multi-frequency with coded excitation for elastography （TFCCE） was proposed. TFCCE adopts the chirp signal excitation scheme and strikes a balance in the selection of sub-signal bandwidth, the bandwidth overlap and the number of sub-strain image based on theoretical derivation, so as to further improve the quality of elastic image. Experiments have proved that, compared with the other optimizing methods, the elastographyic signal-to-noise ratio（Re-SN） and contrast-to-noise ratio（Re-CN） are improved significantly with different echo signal-to-noise ratios （ReSN） and attenuation coefficients. When ReSN is 50 dB, compared with short pulse, Rc-SN and Re-CN obtained by TFCCE increase by 53% and 143%, respectively. Moreover, in a deeper investigation （85-95 mm）, the image has lower strain noise and clear details. When the attenuation coefficient is in the range of 0-1 dB/（cm.MHz）, Re-SN and Re-CN obtained by TFCCE can be kept in moderate ranges of 5〈Re-SN〈6.8 and 11.4〈Re-CN〈15.2, respectively. In particular, for higher tissue attenuation, the basic image quality cannot be ensured with short pulse excitation, while mediocre quality strain figure can be obtained by TFCCE. Therefore, the TFCCE technology can effectively improve the elastography quality and can be applied to ultrasonic clinical trials.

A Morphological Compounding Analysis of Hausa Registers Use in Nigerian Cell-phone Market

This study aims to find the compound registers that are used among the Farm-Centre cell-phone marketers,analyse their compounding morphological structures,and explain the meaning they convey.The Farm-Centre Cell-phone Market is located in Kano metropolis,the largest city of Northern Nigeria.The study employs an ethnographic method of data collection and adopts Abubakar(2000)as a model of approach when analysing the structures of the compound registers.It is found that the registers have the following six morphological compound structures:(i)Genitive-based compounds[LG+N]N,(ii)Noun-based compounds[N+GL+N]N,(iii)Adjective-based compounds[Adj+N]N,(iv)Diminutive-based compounds[Dim+N]N,(v)Particle dà‘with’compounds[dà+N]N,(vi)Verb-based compounds[V+VN/Prep]V.Moreover,the registers are so special among the marketers because they convey meanings that are irrelevant to the conventional meanings known by the general speakers of the Hausa language.

Derivation Versus Compounding

In English language,affixation is a significant way of forming new words,This essay intends to explore the concepts of two fundamental ways of forming new words,namely,derivation and compounding.They are different in a lot of cases,yet,it is also argued that there is a clear dividing line between compounding and derivation.

Effects of Different Compounding of Formulae on Content of Gardenoside in Yin Chen Hao Decoction

In order to observe the effects of the ground and intact Zhi Zi (Fructus Gardeniae) and different combinations of the ingredients and refined single Chinese drug granules in Yin Chen Hao Decoction compound prescription on the contents of gardenoside (an effective component of the prescription), the contents of gardenoside were determined with reversed phase high performance liquid chromatography (HPLC), with acetonitrile-water (15:85) as mobile phase, at wave length 238nm. The results indicated that the gardenoside-decocted-out rates in the decoctions prepared by different combinations of the ingredients with the ground Zhi Zi (Fructus Gardeniae) all were higher significantly than those in the decoction with intact Zhi Zi (Fructus Gardeniae), and generally, different combinations of the ingredients in the decoction had only little effect on the gardenoside-decocted-out rate.

A novel fluorescent labeling compound for GluN2A containing N-methyl-D-aspartate receptors identified by autodisplay-based screening

Autodisplay of N-methyl-D-aspartate(NMDA)receptor[1]ligand binding domains(LBDs)was done by inserting the coding sequence for each LBD[2]into a plasmid for maximized autotransporter-mediated expression(pMATE)between the coding sequences of signal peptide and translocator domain[3](Figs.1A and S1).Surface display and functionality of LBDs was confirmed by protease accessibility and radioligand binding(Figs.S2 and S3).This is discussed in more detail in the Sections S1.1S1.5 in the Supplementary data.Cells with surface displayed LBDs were applied for a flow cytometry-based binding assay to evaluate fluorescent TCN-201 derivatives[4](Figs.1B,S4,and S5).More detailed information about the structural prerequisites of TCN-201 derivatives for interacting with the modulatory binding site and synthesis of fluorescent derivatives is given in the Sections S1.6 and S1.7 in the Supplementary data.

Assessment of electrostatic discharge sensitivity of nitrogen-rich heterocyclic energetic compounds and their salts as high energy-density dangerous compounds:A study of structural variables

Nitrogen-rich heterocyclic energetic compounds(NRHECs)and their salts have witnessed widespread synthesis in recent years.The substantial energy-density content within these compounds can lead to potentially dangerous explosive reactions when subjected to external stimuli such as electrical discharge.Therefore,developing a reliable model for predicting their electrostatic discharge sensitivity(ESD)becomes imperative.This study proposes a novel and straightforward model based on the presence of specific groups(-NH_(2) or-NH-,-N=N^(+)-O^(-)and-NNO_(2),-ONO_(2) or-NO_(2))under certain conditions to assess the ESD of NRHECs and their salts,employing interpretable structural parameters.Utilizing a comprehensive dataset comprising 54 ESD measurements of NRHECs and their salts,divided into 49/5 training/test sets,the model achieves promising results.The Root Mean Square Error(RMSE),Mean Absolute Error(MAE),and Maximum Error for the training set are reported as 0.16 J,0.12 J,and 0.5 J,respectively.Notably,the ratios RMSE(training)/RMSE(test),MAE(training)/MAE(test),and Max Error(training)/Max Error(test)are all greater than 1.0,indicating the robust predictive capabilities of the model.The presented model demonstrates its efficacy in providing a reliable assessment of ESD for the targeted NRHECs and their salts,without the need for intricate computer codes or expert involvement.

Organic Compounds Possessing the Plastic Crystalline Phase: Calculation of Their Fusion Enthalpies

For the first time, for different organic and inorganic compounds possessing the plastic crystalline phase, a new semiempirical equation describing dependence of their fusion enthalpies on such physico-chemical quantities as normal melting temperature, surface tension, molar volume and critical molar volume is received on the base of the principle of corresponding states and the energy equipartition theorem. Moreover, the proposed equation allows one to take into account the particularities of one-particle molecular rotation in the plastic crystalline phase.

Pt-based intermetallic compound catalysts for the oxygen reduction reaction:From problems to recent developments

Proton exchange membrane fuel cells(PEMFCs)are promising next-generation energy conversion devices with advantages including high energy conversion efficiency,low noise,and environmental friendliness.On the PEMFC cathode,the oxygen reduction reaction(ORR)relies heavily on Pt-based catalysts,where PtM_(x)(M stands for transition metal)intermetallic compounds(IMCs)are considered the best choice to enhance the catalytic activity.However,problems such as inadequate catalytic activity,high cost,and insufficient durability,etc.still hamper its commercialization.The optimizations of the catalyst structure,the improvements in the preparation process,and the understanding of the reaction mechanism are of great value.The developments of cathodic oxygen reduction catalysts for PEMFCs will also focus on improving the catalytic activity of intermetallic compound nanoparticles,the utilization rate,and the durability of Pt.Controlling the particle size and particle/carrier interaction remain key issues for future research.The catalyst reaction mechanism,the surface changes of the nanoparticles of Pt(111)face before and after the catalytic reaction,and the targeted regulation of the adsorption strength between the IMCs and oxygen-containing intermediates adjusted by transition metals need to be investigated more specifically and directly.At the application level,the expression of catalyst properties in the catalyst membrane electrode and reactor are the keys to the performance of PEMFCs.Therefore,researches on PEMFCs are still systematic works.This paper summarized the recent process toward the optimization of catalyst preparation,the exploration of new catalysts,and the new understanding of the mechanism.Given the reference to the development of PEMFCs,future research can start from the existing problems,solve the shortcomings of the catalyst,and promote the practical application of PEMFCs.