Sustained oxidation of Tea-Fe(III)/H2O2 simultaneously achieves sludge reduction and carbamazepine removal: The crucial role of EPS regulation.

Establishing an economic and sustained Fenton oxidation system to enhance sludge dewaterability and carbamazepine (CBZ) removal rate is a crucial path to simultaneously achieve sludge reduction and harmless. Leveraging the principles akin to "tea making", we harnessed tea waste to continually release tea polyphenols (TP), thus effectively maintaining high level of oxidation efficiency through the sustained Fenton reaction. The results illustrated that the incorporation of tea waste yielded more favorable outcomes in terms of water content reduction and CBZ removal compared to direct TP addition within the Fe(III)/hydrogen peroxide (H2O2) system. Concomitantly, this process mainly generated hydroxyl radical (•OH) via three oxidation pathways, effectively altering the properties of extracellular polymeric substances (EPS) and promoting the degradation of CBZ from the sludge mixture. The interval addition of Fe(III) and H2O2 heightened extracellular oxidation efficacy, promoting the desorption and removal of CBZ. The degradation of EPS prompted the transformation of bound water to free water, while the formation of larger channels drove the discharge of water. This work achieved the concept of treating waste with waste through using tea waste to treat sludge, meanwhile, can provide ideas for subsequent sludge harmless disposal.

Integrated traditional Chinese and Western medicine in the prevention and treatment of non-alcoholic fatty liver disease: future directions and strategies.

Traditional Chinese medicine (TCM) has been widely used for several centuries for metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). At present, NAFLD has become the most prevalent form of chronic liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. However, there is still a lack of effective treatment strategies in Western medicine. The development of NAFLD is driven by multiple mechanisms, including genetic factors, insulin resistance, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, gut microbiota dysbiosis, and adipose tissue dysfunction. Currently, certain drugs, including insulin sensitizers, statins, vitamin E, ursodeoxycholic acid and betaine, are proven to be beneficial for the clinical treatment of NAFLD. Due to its complex pathogenesis, personalized medicine that integrates various mechanisms may provide better benefits to patients with NAFLD. The holistic view and syndrome differentiation of TCM have advantages in treating NAFLD, which are similar to the principles of personalized medicine. In TCM, NAFLD is primarily classified into five types based on clinical experience. It is located in the liver and is closely related to spleen and kidney functions. However, due to the multi-component characteristics of traditional Chinese medicine, its application in the treatment of NAFLD has been considerably limited. In this review, we summarize the advances in the pathogenesis and treatment of NAFLD, drawn from both the Western medicine and TCM perspectives. We highlight that Chinese and Western medicine have complementary advantages and should receive increased attention in the prevention and treatment of NAFLD.

Screening of Core Prescriptions for Tremors Based on Integrated Strategy of "Empirical Prescriptions in Ancient Books-medical Cases by Prestigious Doctors-computational Analysis" / 中国实验方剂学杂志

ObjectiveBased on the integrated strategy of "empirical prescriptions in ancient books-medical cases by prestigious doctors-computational analysis"， this study aims to explore and analyze the prescriptions and medical cases for treating tremors in traditional Chinese medicine （TCM）， predict their efficacy， and obtain the core prescriptions for treating tremors in TCM， providing references for clinical application and new drug development. MethodThe Chinese Medicine Prescription Database and the China National Knowledge Infrastructure （CNKI） were searched for relevant prescriptions and medical cases for treating tremors in TCM to establish a database of prescriptions for tremors. The Traditional Chinese Medicine Inheritance Computer System （V3.0） was used to analyze and explore the medication rules including drug frequency， properties， flavor， meridian tropism， and pharmacological effects， as well as core drugs and formula associations. A multi-target drug efficacy prediction platform based on network robustness was used to evaluate the predicted efficacy of the core prescriptions obtained. Based on the integration of ancient prescriptions， prestigious doctors' medical cases， and network analysis results， the priority level of the developed prescriptions was determined through comprehensive evaluation. ResultA total of 81 ancient prescriptions were screened， involving 246 drugs， and 171 prescriptions were screened from prestigious doctors' medical cases， involving 278 drugs. The frequently used TCM drugs were mostly warm in nature and sweet in flavor， mainly acting on the liver， spleen， and kidney meridians. In terms of efficacy， they were mainly effective in tonifying deficiency， soothing liver and extinguishing wind， activating blood and resolving blood stasis， clearing heat， and resolving exterior. Through association rules and K-means clustering， the core prescriptions were composed of high-frequency drugs such as Glycyrrhizae Radix et Rhizoma， Ginseng Radix et Rhizoma， Astragali Radix， Atractylodis Macrocephalae Rhizoma， Angelicae Sinensis Radix， Poria， Gastrodiae Rhizoma， and Uncariae Ramulus Cum Uncis. Drug combinations mainly focused on tonifying Qi and nourishing blood， with the additional functions of calming wind and dredging collaterals. Clustering analysis of core prescriptions from ancient prescriptions and prestigious doctors' medical cases， as well as multi-target drug efficacy prediction， showed that Combination 1 had the highest disturbance score on the disease network. Furthermore， comparative analysis revealed consistent results with both the analysis of ancient prescriptions and prestigious doctors' medical cases， indicating its optimal development potential based on theoretical inheritance and empirical practice. In comparison， Combinations 3， 2， and 4 were less utilized in contemporary clinical practice， with lower rankings in network disturbance scores， suggesting that their development value still warranted further exploration. ConclusionTCM clinical treatment of tremors emphasizes the regulation of the liver， spleen， and kidney. In line of syndrome differentiation， drugs potent in soothing liver， extinguishing wind， activating blood， and resolving blood stasis are added based on deficiency-tonifying drugs. The core prescriptions based on Glycyrrhizae Radix et Rhizoma， Angelicae Sinensis Radix， Paeoniae Radix Alba， Astragali Radix， Poria， and Atractylodis Macrocephalae Rhizoma （combination 1） have the highest potential development value. The integrated strategy "empirical prescriptions in ancient books-medical cases by prestigious doctors-computational analysis" can be used for the screening of candidate prescriptions for new TCM drugs.

Multidirectional insights into the phytochemical, biological, and multivariate analysis of extracts from the aerial part of Swertia perennis Linnaeus.

Swertia perennis Linnaeus (SP) has been utilised to treat gastritis. We report the qualitative and quantitative phytochemical analysis, antioxidant and enzyme inhibitory activities of SP. The correlation between the biological activities and total bioactive contents of the extracts was also studied via multivariate analysis. Methanol extract contained many active compounds and exhibited good antioxidant activity. Therefore, this was selected for further phytochemical profiling and stability studies. Fourteen compounds were identified by ultra-performance liquid chromatography-electrospray ionisation-orbitrap-mass spectrometry for the first time from this plant. Iridoids, xanthones, and flavonoids were the main components. Methanol extract exhibited good stability and antioxidant capacity in stability studies, with low toxicity, and showed a protective effect on the oxidation of olive and sunflower oils. SP has the potential to be developed and used as an antioxidant, or as urease and XO inhibitors, and its methanol extract could be used as a natural oil stabiliser.

[Multi-component content determination of Dracocephalum tanguticum by quantitative analysis of multi-components by single-marker].

This study aims to establish a method for the simultaneous determination of 7 active components in Dracocephalum tanguticum and to evaluate the quality of medicinal materials from different habitats. The method was established with high performance liquid chromatography(HPLC) and the gradient elution was performed with the mobile phase of acetonitrile-methanol-0.2% phosphoric acid solution at a column temperature of 35 ℃, an injection volume of 15 µL, and a flow rate of 0.6 mL·min~(-1). The detection wavelength was set as 215 nm. With rosmarinic acid as the internal reference, the relative correction factors and the content of other 6 components were calculated. The results were compared with those obtained with the external standard method. The results showed that the samples from Huangzhong county, Qinghai province had the best quality, with the highest content of p-hydroxybenzoic acid, cosmosiin, rosmarinic acid, oleanolic acid, and ursolic acid(9.29, 12.14, 6.02, 3.11, 17.67 mg·g~(-1) respectively). The samples from Chaya county, Tibet autonomous region ranked the second, with the highest content of betulin and betulinic acid(15.53, 7.17 mg·g~(-1), respectively). The method is accurate, reliable, and repeatable and suitable for the simultaneous determination of multiple components in D. tanguticum. The content of functional components varied in the samples from different producing areas and can be used as the indicator for the quality evaluation of medicinal materials.

Phytochemical Analysis, Antioxidant and Enzyme-Inhibitory Activities, and Multivariate Analysis of Insect Gall Extracts of Picea koraiensis Nakai.

Picea koraiensis Nakai (PK) is an evergreen tree. It plays an important role in landscaping and road greening. Insect galls of PK are formed by parasitism of the adelgid Adelges laricis. Except for phenolics, other chemical constituents and biological activity of insect gall from PK are still unknown. Thus, here, we performed phytochemical and biological activity analyses of PK insect gall extracts, aiming to turn waste into treasure and serve human health. PK insect gall extracts were prepared using seven solvents. Antioxidant activities of the extracts were examined via antioxidant assays (radical and oxidizing substance quenching, metal chelating, and reducing power). The inhibitory activities of the extracts were determined toward the key human-disease-related enzymes α-glucosidase, α-amylase, cholinesterase, tyrosinase, urease, and xanthine oxidase. The content of numerous active constituents was high in the methanol and ethanol extracts of PK insect gall, and these extracts had the highest antioxidant and enzyme-inhibitory activities. They also showed excellent stability and low toxicity. These extracts have potential for use as stabilizers of olive and sunflower seed oils.

The role of the chloroplast localised phosphate transporter GmPHT4;10 gene in plant growth, photosynthesis and drought resistance.

In view of the importance of inorganic phosphate to plant growth and development, the role of phosphate transporters responsible for absorption and transportation in crops has attracted increasing attention. In this study, bioinformatics analysis and subcellular localisation experiment showed that GmPHT4;10 is a member of PHT4 subfamily of phosphate transporters and located in chloroplasts. The gene was induced by phosphate deficiency and drought, and was the highest in leaves. After GmPHT4;10 gene was replenished to AtPHT4;5 gene deletion mutant lines (atpht4;5 ), the phenotype of the transgenic lines was basically recovered to the level of wild-type, but there were significant differences in phosphate content and photosynthetic indicators between wild-type and revertant lines. Meanwhile, the difference of proline content and catalase activity between the two lines also indicated that GmPHT4;10 gene and its orthologous gene AtPHT4;5 were different in drought resistance and drought resistance mechanism. After overexpression of GmPHT4;10 gene in Arabidopsis thaliana , more phosphate and proline were accumulated in chloroplasts and catalase activity was increased, thus improving photosynthesis and drought resistance of plants. The results further supplement the cognition of PHT4 subfamily function, and provides new ideas and ways to improve photosynthesis by revealing the function of chloroplast phosphate transporter.

Amphiphilic Dendrimer Doping Enhanced pH-Sensitivity of Liposomal Vesicle for Effective Co-delivery toward Synergistic Ferroptosis-Apoptosis Therapy of Hepatocellular Carcinoma.

Ferroptosis, characterized by the accumulation of reactive oxygen species and lipid peroxides, has emerged as an attractive strategy to reverse drug resistance. Of particular interest is the ferroptosis-apoptosis combination therapy for cancer treatment. Herein, a nanoplatform is reported for effective co-delivery of the anticancer drug sorafenib (S) and the ferroptosis inducer hemin (H), toward synergistic ferroptosis-apoptosis therapy of advanced hepatocellular carcinoma (HCC) as a proof-of-concept study. Liposome is an excellent delivery system; however, it is not sufficiently responsive to the acidic tumor microenvironment (TME) for tumor-targeted drug delivery. The pH-sensitive vesicles are therefore developed (SH-AD-L) by incorporating amphiphilic dendrimers (AD) into liposomes for controlled and pH-stimulated release of sorafenib and hemin in the acidic TME, thanks to the protonation of numerous amine functionalities in AD. Importantly, SH-AD-L not only blocked glutathione synthesis to disrupt the antioxidant system, but also increased intracellular Fe2+ and ·OH concentrations to amplify oxidative stress, both of which contribute to enhanced ferroptosis. Remarkably, high levels of ·OH also augmented sorafenib-mediated apoptosis in tumor cells. This study demonstrates the efficacy of ferroptosis-apoptosis combination therapy, as well as the promise of the AD-doped TME-responsive vesicles for drug delivery in combination therapy to treat advanced HCC.

Phytochemical profiling and antioxidant, enzyme-inhibitory, and toxic activities of extracts from Adonis ramosa Franch.

This study investigated the content and biological activity of three solvent extracts of Adonis ramosa Franch (AR), which contains 12 types of phytochemicals. The overall yield and total protein content of the aqueous extract were the highest, and it exhibited the highest hydroxyl and superoxide radical-scavenging abilities, copper chelating abilities, and cupric reducing antioxidant capacity. Ethanol extract had the highest total phenolic, flavonoid, and carbohydrate contents, and it showed the highest iron chelating activity, and HClO- and nitrite-scavenging abilities. Methanol AR extract contained the highest total steroid and tannin contents; it also demonstrated high radical- and reactive oxygen species-scavenging abilities and had the best ferric reducing antioxidant power, which allowed it to effectively prevent ß-carotene bleaching. Methanol extract also showed good stability and low toxicity. All tested solvent extracts of AR exhibited weak enzyme-inhibitory activities for four enzymes (α-glucosidase, α-amylase, acetylcholinesterase and butyrylcholinesterase). Overall, AR can serve as a natural antioxidant.

Astaxanthin alleviates palmitic acid-induced hindrance of porcine oocyte maturation.

Increased palmitic acid (PA) levels have been found in females with reduced fertility due to metabolic disorders. However, effective antioxidant astaxanthin (AXE) might positively affect animal reproduction. Therefore, the present study was designed to evaluate the impact of a high concentration of PA on oocyte maturation and the possible protective effect of AXE against high PA concentration in pigs. Firstly, different concentrations (0.2, 0.5, 0.8 mM) of PA were conducted on in vitro maturation (IVM) of pig oocytes (PA0.2, PA0.5, and PA0.8), while no addition of PA was performed as the control group (Ctrl). Results showed that the cumulus cell expansion index (CCEI) was lower in PA0.5 and PA0.8 groups compared to Ctrl group (p < .05). In PA0.5 group, not only did the percentage of matured oocytes with the first polar body (PB1) reduced, that with more oocytes arrested at germinal vesicle (GV) stage (53.44% ± 7.16% vs. 20.93% ± 5.16%, p < .05), but also a higher number of transzonal projections (TZPs) was observed in PA0.5 than Ctrl group. Besides, supplement of PA resulted in a dose-dependent decrease in mitochondrial activity. Although no difference of lipid content was observed between PA0.5 and Ctrl groups, the lipid content was at a higher level in PA0.2 group than in the other three groups. Hence, concentration of 0.5 mM of PA was performed in the following experiments, and 2.5 µM AXE carried out to investigate the possible relief effects of PA (PA0.5 + AXE). Results showed that the percentage of matured oocytes with PB1 was higher in PA0.5 + AXE than in PA0.5 group (63.43% ± 1.50% vs. 55.33% ± 0.81%, p < .01), and ROS levels both in oocytes and their cumulus cells (CCs) reduced in PA0.5 + AXE when compared to PA0.5 group. In addition, the rate of CCs with apoptosis decreased in PA0.5 + AXE, and the expression level of caspase 3 and BAX was lower than PA0.5 group. In conclusion, the maturation of pig oocytes was inhibited by the high concentration of PA; however, this negative effect of PA-induced might be relieved by the supplement of AXE.

Studies on improving semen quality and increasing pregnancy chances through the in vitro addition of L-carnitine and coenzyme Q10 to semen in patients with asthenozoospermia.

BACKGROUND: At present, L-carnitine (LC) and coenzyme Q10 (CoQ10), as used clinically to treat male infertility caused by asthenozoospermia (ASZ) is still mainly administered orally, but some patients with ASZ still show no significant improvement in sperm motility and spouse pregnancy rate. Prodom is a device used to assist reproduction, which is temporarily fitted onto the penis to facilitate conception by helping the wife inject a certain drug into the vagina. This study used Prodom-assisted LC/CoQ10 in the treatment of patients with ASZ and evaluated the effect of this method on sperm motility and clinical pregnancy, with the goal of finding a comfortable, low-cost, effective method. RESULTS: During the trial period, 232 cases completed the trial, while 25 cases did not. During in vitro testing, the progressive sperm motility in the LC group, CoQ10 group, LC combined with CoQ10 group, and the semen blank control group was 24.3 ± 4.6% and 38.1 ± 5.1%, 23.0 ± 4.8% and 36.9 ± 4.4%, 28.4 ± 5.0% and 43.8 ± 5.4%, 19.7 ± 4.4% and 26.0 ± 4.9%, respectively. There were statistically significant differences in progressive sperm motility among the groups (all P values < 0.05). The pregnancy rates of the Prodom-assisted LC treatment group, Prodom-assisted CoQ10 treatment group, Prodom-assisted LC combined with CoQ10 treatment group, and oral LC combined with CoQ10 treatment group in the clinical treatment stage were 38.2, 35.4, 57.1, and 30.3%, respectively; the time to conception was 6.1 ± 1.8, 6.2 ± 1.8, 3.4 ± 0.9, and 7.9 ± 2.0, months respectively; and the treatment costs were $2350 ± 457, $2455 ± 434, $1348 ± 411, and $2684 ± 334, respectively. The differences in pregnancy rate, time to conception, and treatment costs among the groups were statistically significant (all P values < 0.05). CONCLUSIONS: The supplementation of in vitro semen with LC/CoQ10 can improve sperm motility. LC/CoQ10 injected into the spouse's vagina with the assistance of a Prodom can increase the pregnancy rate, shorten the time to conception, and reduce the cost of treatment in patients with ASZ. TRIAL REGISTRATION: ChiCTR2000040349 (registry: http://www.chictr.org.cn/ ). Date of registration: November 28, 2020.

RéSUMé: CONTEXTE: À l'heure actuelle, la L-carnitine (LC) et le coenzyme Q10 (CoQ10), tels qu'utilisés en clinique pour traiter l'infertilité masculine due à une asthénozoospermie (AZS), sont encore principalement administrés par voie orale, mais certains patients atteints d'AZS ne montrent pas toujours d'amélioration significative de la motilité des spermatozoïdes, ni de grossesse chez la conjointe. Prodom™ est. un dispositif utilisé pour aider à la reproduction, qui est. temporairement installé sur le pénis pour faciliter la conception en aidant la femme à injecter certains médicaments dans le vagin. Cette étude a utilisé une association CL + CoQ10 assistée par Prodom™ pour traiter des patients atteints d'AZS et a évalué l'effet de cette méthode sur la mobilité des spermatozoïdes et la grossesse clinique, dans le but de trouver une méthode confortable, peu coûteuse et efficace. RéSULTATS: Au cours de cet essai thérapeutique, 232 cas sont allés au bout de l'étude, alors que 25 se sont arrêtés. Au cours des tests in vitro, la mobilité progressive des spermatozoïdes dans le groupe LC, le groupe CoQ10, le groupe CL + CoQ10 et dans le groupe témoin de sperme, était respectivement de 24,3 ± 4,6% et 38,1 ± 5,1%, de 23,0 ± 4,8% et 36,9 ± 4,4%, de 28,4 ± 5,0% et 43,8 ± 5,4%, et de 19,7 ± 4,4% et 26,0 ± 4,9%. La mobilité progressive des spermatozoïdes était significativement différentes entre les groupes (toutes les valeurs de P < 0,05). Les taux de grossesse dans le groupe traité par LC assistée par Prodom™, dans le groupe traité par CoQ10 assisté par Prodom™, dans le groupe traité par une association CL + CoQ10 assistée par Prodom™, et dans le groupe traité cliniquement par CL par voie orale associée au CoQ10, étaient respectivement de 38,2%, 35,4%, 57,1% et 30,3%; le délai de conception était respectivement de 6,1 ± 1,8, 6,2 ± 1,8, 3,4 ± 0,9 et 7,9 ± 2,0, mois; et les coûts de traitement étaient respectivement de 2350 ± 457 $, 2455 ± 434 $, 1348 ± 411 $ et 2684 ± 334 $. Les différences dans le taux de grossesse, le délai de conception et les coûts de traitement entre les groupes étaient statistiquement significatives (toutes les valeurs de P < 0,05). CONCLUSIONS: La supplémentation en LC/CoQ10 du sperme in vitro peut améliorer la mobilité des spermatozoïdes. L'association LC + CoQ10 injectée dans le vagin de la conjointe avec l'aide d'un Prodom™ peut augmenter le taux de grossesse, raccourcir le délai de conception et réduire le coût du traitement chez les patientes atteints d'AZS. Numéro d'enregistrement de l'essai ChiCTR2000040349 (registre: http://www.chictr.org.cn/ ). Date d'enregistrement: 28 novembre 2020.

Sini powder with paroxetine ameliorates major depressive disorder by modulating circadian rhythm: A randomized, double-blind, placebo-controlled trial.

Circadian rhythm disorder is a significant risk factor for mental diseases, and the recovery of circadian rhythm function has gradually become a signal of effective antidepressant therapy. Sini powder (SNP) is a classical, traditional Chinese formula for depression treatment. However, few clinical reports have been recorded. This randomized, double-blinded, controlled trial (ChiCTR1900022700) aimed to explore the efficacy of SNP on depression via regulating circadian rhythm. In total, 36 patients with major depressive disorder (MDD) were enrolled for 4-weeks medication and 6-weeks follow-up. HAMD-24 score and circadian rhythm index, including dim light melatonin onset (DLMO) and phase angle difference (PAD), were included in the assessment. DLMO and PAD were statistically significant in the SNP group after 4 weeks of treatment (p < .05) and with greater improvement in DLMO (p = .03). In addition, DLMO and the HAMD-24 score showed a positive correlation (p < .05); the HAMD-24 score degree decreased significantly over time (p < .001). Similarly, interaction effects were shown significantly between group and time (p = .049). The duration of SNP supplementation was relatively short, and the sample size was relatively small. SNP granules combined with paroxetine tablets have definite efficacy in improving the circadian rhythms of MDD patients, reflecting the therapeutic advantages of traditional Chinese medicine as antidepressants.

Safety Assessment of Canola Oil Extracted by Aid of Pulsed Electric Field: Genetic, Acute and Subacute Toxicity.

Pulsed electric field (PEF) is a nonthermal technology resulting in the rupture of cell membranes and increasing the electrical conductivity and the permeability of intracellular material. There was little work about the safety of food treated by PEF. The acute, subacute oral, and genetic toxicities were investigated to explore the safety of canola oil extracted by aid of PEF treatment (PTCO). The results showed that no negative consequences were caused by PEF. PTCO was regarded as practically non-toxic with a LD50 higher than 40 g/kg bw. No oil intake-related mortality, clinical, weight gain and organ coefficient abnormalities were observed. The histopathological symptoms indicated a mild load but not obvious toxicities on liver and kidney. The 28-day subacute toxicity test confirmed that less than 10 g/kg·d bw of oil intake did not exhibit any intake-related changes in physical, physiological, biochemical, hematological, and histopathological signs. The less than 4 of atherosclerosis index suggested that no risk of cardiovascular disease caused by PTCO intake. It was speculated that the PEF treatment would not cause any safety issues to food products.

The therapeutic mechanism of PuRenDan for the treatment of diabetic nephropathy: Network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Purendan (PRD), as a Chinese medicinal formula, behaves remarkable therapeutic effects on diabetes and complications in clinical and experimental research. However, the underlying pharmacological mechanism in the treatment of diabetic nephropathy (DN) is still unclear. AIMS: To investigate the therapeutical effects of PRD on DN and to explore its pharmacological mechanisms using network pharmacology and experimental verification. MATERIALS AND METHODS: The active compounds and putative targets in PRD, and disease-related targets of DN were extracted from public databases. The key targets were identified through the protein-protein interaction (PPI) network and module analysis. The GO and KEGG enrichment analysis were performed to discover potential pharmacological mechanisms. The expression of the key targets was detected in kidney tissue in Gene Expression Omnibus (GEO) dataset. The affinity between key proteins and corresponding compounds was evaluated by molecular docking and validated by the surface plasmon resonance (SPR) assay. The indicators on major pathways and hub genes were verified by in vivo experiments. RESULTS: In network pharmacology, 137 common targets in PRD for DN treatment were screened. The key targets and main signaling pathways including AGE-RAGE and lipid pathways were identified. The statistical difference in the expression of the key targets was verified in GSE96804 database, confirming the association with DN. The docking scores obtained from molecular docking illustrated good binding force between hub proteins and active compounds. And the good component-protein affinities were validated by SPR assay. Furthermore, the results of animal experiment indicated that PRD could ameliorate the level of serum glucose and renal function in rat model. It could regulate the expression of hub targets (AKT1, MAPK3, and STAT3) and improve indicators related with oxidative stress and lipid metabolism. CONCLUSION: The key targets and major signaling pathways in the treatment of PRD on DN were identified. The mechanism might relate to regulation of oxidative stress and lipid metabolism.

Study on the Active Constituents and Molecular Mechanism of Zhishi Xiebai Guizhi Decoction in the Treatment of CHD Based on UPLC-UESI-Q Exactive Focus, Gene Expression Profiling, Network Pharmacology, and Experimental Validation.

As one of the most common clinical cardiovascular diseases (CVDs), coronary heart disease (CHD) is the most common cause of death in the world. It has been confirmed that Zhishi Xiebai Guizhi decoction (ZXGD), a classical prescription of the traditional Chinese medicine (TCM), has achieved certain effects in the treatment of CHD; however, the mechanism still remains controversial. In this paper, an integrated approach, including UPLC-UESI-Q Exactive Focus, gene expression profiling, network pharmacology, and experimental validation, was introduced to systematically investigate the mechanism of ZXGD in the treatment of CHD. First, UPLC-UESI-Q Exactive Focus was applied to identify the chemical compounds of ZXGD. Then, the targets of the components for ZXGD were predicted by MedChem Studio software embed in the integrative pharmacology-based research platform of TCM, and the differentially expressed genes (DEGs) of CHD were obtained by gene expression profiling in gene expression omnibus database. The common genes of the above two genes were obtained by Venn analysis as the targets of GXGD in treatment with CHD. Third, the core targets were screened out by protein-protein interaction network analysis, and the kyoto encyclopedia of genes and genomes pathway enrichment analysis was performed by the database for annotation, visualization, and integrated discovery bioinformatics resources. After that, the formula-herb-compound-target-pathway network was constructed to explore the mechanism of ZXGD in the treatment of CHD. Finally, molecular docking and the vitro experiment were carried out to validate some key targets. As a result, a total of 39 compounds, 12 core targets, and 4 pathways contributed to ZXGD for the treatment of CHD. This study preliminarily provided a foundation for the study on the mechanism against CHD for ZXGD and may be a reference for the compatibility mechanism and the extended application of TCM compound prescription.

Purendan alleviates non-alcoholic fatty liver disease in aged type 2 diabetic rats via regulating mTOR/S6K1/SREBP-1c signaling pathway.

Older people are more likely to develop insulin resistance and lipid metabolism disorders. Purendan (PRD) is a clinically verified traditional Chinese medicine compound, which plays an obvious role in regulating lipid metabolism disorder and improving insulin sensitivity. Our study aimed to investigate the efficacy and mechanism of PRD on aged type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) rats. Sprague-Dawley rats (13 months) were fed with high-fat diet (HFD) and injected with low-dose STZ to replicate T2DM model. PRD was treated at three concentrations with metformin as a positive control. After administration, blood and liver tissue samples were collected to measure glucose metabolism indexes such as serum glucose and insulin, as well as lipid metabolism indexes such as TC, TG, LDL, HDL and FFA. Liver fat accumulation was observed by HE staining and oil red O staining. And protein expression levels of mTOR, p-mTOR, S6K1, p-S6K1 and SREBP-1c were detected by western blot. After PRD treatment, not only the insulin sensitivity and insulin resistance were significantly improved, but also the TC, TG, LDL, FFA, AST and ALT in serum and the lipid accumulation in liver tissue were significantly decreased. Moreover, PRD significantly down-regulated the expression of p-mTOR, p-S6K1 and SREBP-1c in liver tissues. In conclusion, PRD can alleviate NAFLD in aged T2DM rats by inhibiting the mTOR /S6K1/ SREBP-1c pathway.

A Novel Method for Identifying Parkin Binding Agents in Complex Preparations of Herbal Medicines.

Parkin is a crucial E3 ubiquitin ligase for initiating mitophagy through the PINK1/Parkin pathway. Regulating the expression and activity of parkin can remedy mitophagy and human disease. We developed an efficient method to isolate natural parkin ligands from herbal medicines by combining centrifugal ultrafiltration and liquid chromatography/mass spectrometry. The heterologous expression technology identified functionally active and pure parkin proteins. After evaluating the reliability of the method using DL-selenomethionine and DL-dithiothreitol as positive controls, this method was successfully applied to capture parkin ligands from Polygoni Cuspidati Rhizoma et Radix and Sophorae Flavescentis Radix. LC/MS identified seven novel parkin-targeting compounds, namely, 7,4'-dihydroxy-5-methoxy-8-(γ, γ-dimethylallyl)-flavanone, kushenol I, kurarinone, sophoraflavanone G, torachrysone-8-O-glucoside, apigenin, and emodin, supported by the molecular docking analysis. Five of the seven novel compounds (kushenol I, kurarinone, sophoraflavanone G, apigenin, and emodin) can activate parkin in in vitro autoubiquitination assays. Meanwhile, kushenol I and kurarinone had antisteatosis activity in fat emulsion-damaged human hepatocytes. These results confirmed the effectiveness of the method for identifying parkin ligands from complex preparations, useful to advance drug discovery from medicinal herbs.

Study on the molecular mechanism of Guipi decoction against sleep deprivation based on integrated pharmacology analysis and gene expression profiling.

Sleep disorder is a puzzling and complex health problem, and sleep deprivation (SD) may be a window for studying sleep disorder. Guipi decoction (GPD) is a classic Chinese prescription for the treatment of sleep disorder. However, the mechanism of GPD remains puzzling. In this paper, integrated pharmacological analysis and gene expression profiling were introduced to study the mechanism of GPD in treatment with SD. Firstly, the integrative pharmacology­based research platform of traditional Chinese medicine (TCMIP) was applied to collect chemical compounds and corresponding targets for GPD. Secondly, SD­related targets were obtained by gene expression profiling (GSE56931) from Gene Expression Omnibus (GEO) database. The String database screened the core targets according to protein­protein interaction (PPI) network. Furthermore, kyoto encyclopedia of genes and genomes (KEGG) pathways were carried out based on the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Conclusively, the "formula­herbs­compounds­targets­pathways" network was established to explore the mechanism of GPD in the treatment of SD. In addition, molecular docking was carried out to verify the connection between hub compounds and targets. The results showed that GPD was mainly linked to 44 compounds, 19 targets and 5 pathways. GPD in the treatment of sleep deprivation through metabolic pathways and cAMP signaling pathway, which were related to NR3C1, MAPK3, PPARA and core compounds such as adenosine. This study preliminarily revealed the molecular mechanism of GPD for SD, and lays a foundation for the study of the mechanism against SD for GPD.

Life cycle assessment of sewage sludge treatment and disposal based on nutrient and energy recovery: A review.

With the acceleration of urbanization, the production of urban sludge is increasing rapidly. To minimize resource input and waste output, it is crucial to execute analyses of environmental impact and assessments of sustainability on different technical strategies involving sludge disposal based on Life Cycle Assessment (LCA), which is a great potential mean of environmental management adopted internationally in the 21st century. This review aims to compare the environmental sustainability of existing sludge management schemes with a purpose of nutrient recovery and energy saving, respectively, and also to include the substitution benefits of alternative sludge products. Simultaneously, LCA research regarding the emerging sludge management technologies and sludge recycling (cement, adsorbent, bricks) is analyzed. Additionally, the key aspects of the LCA process are worth noting in the context of the current limitations reviewed here. It is worth emphasizing that no technical remediation method can reduce all environmental damage simultaneously, and these schemes are typically more applicable to the assumed local conditions. Future LCA research should pay more attention to the toxic effects of different sludge treatment methods, evaluate the technical ways of adding pretreatment technology to the 'front end' of the sludge treatment process, and further explore how to markedly reduce environmental damage in order to maximize energy and nutrient recovery from the LCA perspective.

Dynamic Contrast-Enhanced Ultrasound Radiomics for Hepatocellular Carcinoma Recurrence Prediction After Thermal Ablation.

PURPOSE: To develop a radiomics model based on dynamic contrast-enhanced ultrasound (CEUS) to predict early and late recurrence in patients with a single HCC lesion ≤ 5 cm in diameter after thermal ablation. PROCEDURES: We enrolled patients who underwent thermal ablation for HCC in our hospital from April 2004 to April 2017. Radiomics based on two branch convolution recurrent network was utilized to analyze preoperative dynamic CEUS image of HCC lesions to establish CEUS model, in comparison to the conventional ultrasound (US), clinical, and combined models. Clinical follow-up of HCC recurrence after ablation were taken as reference standard to evaluate the predicted performance of CEUS model and other models. RESULTS: We finally analyzed 318 patients (training cohort: test cohort = 255:63). The combined model showed better performance for early recurrence than CUES (in training cohort, AUC, 0.89 vs. 0.84, P < 0.001; in test cohort, AUC, 0.84 vs. 0.83, P = 0.272), US (P < 0.001), or clinical model (P < 0.001). For late recurrence prediction, the combined model showed the best performance than the CEUS (C-index, in training cohort, 0.77 vs. 0.76, P = 0.009; in test cohort, 0.77 vs. 0.68, P < 0.001), US (P < 0.001), or clinical model (P < 0.001). CONCLUSIONS: The CEUS model based on dynamic CEUS radiomics performed well in predicting early HCC recurrence after ablation. The combined model combining CEUS, US radiomics, and clinical factors could stratify the high risk of late recurrence.