[Effect of acupotomy on mitophagy mediated by PINK1/Parkin pathway in cartilage of rabbits with knee osteoarthritis].

OBJECTIVE: To observe the effect of acupotomy on mitophagy mediated by PINK1/Parkin pathway in cartilage of rabbits with knee osteoarthritis (KOA), so as to explore its mechanism in inhibiting cartilage damage. METHODS: Twenty-one New Zealand rabbits were randomly divided into normal, model, and acupotomy groups, with 7 rabbits in each group. The KOA rabbit model was established by using the Videman method. Rabbits in the acupotomy group received regular acupotomy treatment around the knee joint nodules or tendons once a week for 3 consecutive weeks. HE staining and transmission electron microscopy were used to observe the morphological and ultrastructural changes in knee joint cartilage of rabbits. Flow cytometry was used to measure the mitochondrial membrane potential (Δψm) and reactive oxygen species (ROS) average fluorescence intensity in chondrocytes. Immunofluorescence was performed to detect the fluorescence intensity of LC3B, PINK1 and Parkin in cartilage tissue. Western blot was conducted to measure the protein expression levels of p62, LC3Ⅱ/Ⅰ, PINK1, and Parkin in cartilage tissue. RESULTS: Compared to the normal group, the model group showed fissures and tissue fibrosis on the surface of rabbit knee joint cartilages, loose distribution of chondrocytes, decreased autophagosomes, and abnormal mitochondrial morphology. The fluorescence intensity of LC3B, PINK1 and Parkin, the expression levels of LC3Ⅱ/Ⅰ, PINK1 and Parkin proteins in cartilage tissue were significantly decreased (P<0.01), while the percentage of chondrocytes with low Δψm, the average fluorescence intensity of ROS, and the expression of p62 protein in cartilage tissue were significantly increased (P<0.01). Compared to the model group, the acupotomy group showed no obvious defects on the surface of rabbit knee joint cartilage, relatively dense distribution of chondrocytes, increased autophagosomes, and relatively normal mitochondrial morphology. The fluorescence intensity of LC3B, PINK1 and Parkin, the expression of LC3Ⅱ/Ⅰ, PINK1 and Parkin proteins in cartilage tissue were significantly increased (P<0.01, P<0.05), while the percentage of chondrocytes with low Δψm, the average fluorescence intensity of ROS, and the expression of p62 protein in cartilage tissue were significantly decreased (P<0.01). CONCLUSION: Acupotomy may promote mitophagy by regulating the PINK1/Parkin pathway, thereby improving cartilage damage in rabbits with KOA.

Triterpenoids from the fruits of Melia toosendan Sieb. et Zucc. with α-glucosidase inhibitory activities.

Four previously unreported tirucallane-type triterpenoids (1-4), together with four known analogues (5-8), were isolated from the fruits of Melia toosendan Sieb. et Zucc. Their planar structures were comprehensively elucidated by detailed analyses of HRESIMS, 1D and 2D NMR spectra data. The relative configurations of 1-4 were determined by NOESY experiments. The comparison of experimental and calculated electronic circular dichroism (ECD) spectra led to the establishment of the absolute configurations of new compounds. All isolated triterpenoids were evaluated for their α-glucosidase inhibitory activities in vitro. Compounds 4 and 5 showed moderate α-glucosidase inhibitory activities with IC50 values of 120.3 ± 5.8 and 104.9 ± 7.1 µM, respectively.

[Effect of needle-knife on chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis based on CircSERPINE2-miR-1271-5P-ERG axis].

OBJECTIVE: To observe the effect of needle-knife on the chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis (KOA) based on the CircSERPINE2-miR-1271-5P-E26 specific transformation-related gene (ERG) axis, and to explore the mechanism of needle-knife for KOA. METHODS: Thirty-six New Zealand white rabbits were randomly divided into a normal group, a model group, a needle-knife group and a sham needle-knife group, 9 rabbits in each group. The rabbits in the model group, the needle-knife group and the sham needle-knife group were treated with modified Videman method to prepare KOA model. After successful modeling, the rabbits in the needle-knife group were treated with needle-knife at cord adhesion and nodules near quadriceps femoris tendon and internal and external collateral ligament on the affected knee joint; the rabbits in the sham needle-knife group were treated with sham needle-knife baside the needle insertion point of the needle-knife group (needle-knife was only inserted, without any operation). The treatment was given once a week, 3 times in total. The Lequesne MG behavioral score was used to evaluate the knee joint damage in each group before and after intervention. After intervention, HE staining and transmission electron microscopy were used to observe the cartilage tissue morphology and ultrastructure of chondrocytes in the knee joint in each group; TUNEL method was used to detect the level of chondrocyte apoptosis in the knee joint; real-time fluorescence quantitative PCR was used to detect the expression of CircSERPINE2, miR-1271-5P and ERG mRNA in knee cartilage tissue in each group. RESULTS: After intervention, compared with the normal group, the Lequesne MG behavioral score in the model group was increased (P<0.01). Compared with the model group and the sham needle-knife group, the Lequesne MG behavioral score in the needle-knife group was decreased (P<0.01). In the model group and the sham needle-knife group, the number of chondrocytes and organelles was decreased, the cell nucleus was shrunk, mitochondria was swelling or disappeared; in the needle-knife group, the number of chondrocytes and organelles was increased, the cell nucleus was not obviously shrunk and the mitochondria was not obviously swelling. Compared with the normal group, the level of chondrocyte apoptosis in the model group was increased (P<0.01); compared with the model group and the sham needle-knife group, the level of chondrocyte apoptosis in the needle-knife group was decreased (P<0.01, P<0.05). Compared with the normal group, the expression of CircSERPINE2 and ERG mRNA in the model group was decreased (P<0.01), and the expression of miR-1271-5P mRNA was increased (P<0.01); compared with the model group and the sham needle-knife group, the expression of CircSERPINE2 and ERG mRNA in the needle-knife group was increased (P<0.01), and the expression of miR-1271-5P mRNA was decreased (P<0.01). CONCLUSION: Needle-knife could reduce the knee joint damage and chondrocyte apoptosis in KOA rabbits, which may be related to up-regulating the expression of CircSERPINE2 and ERG mRNA, and inhibiting the expression of miR-1271-5P mRNA.

[Alkaloids from fruit of Lycium chinense var. potaninii].

Ten alkaloids(1-10) were isolated from the ethyl acetate extract of the fruit of Lycium chinense var. potaninii by silica gel, ODS, and preparative high performance liquid chromatography(HPLC), and identified by NMR and MS as methyl(2S)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(1), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(2), 3-hydroxy-4-ethyl ketone pyridine(3), indolyl-3-carbaldehyde(4),(R)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(5),(R)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-car-baldehyde(6), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(4-hydroxyphenyl)propanoate(7), dimethyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanedioate(8), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoate(9), 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid(10). All the compounds were isolated from the plant for the first time. Among them, compounds 1-3 were new compounds. Compounds 1-9 were evaluated for hypoglycemic activity in vitro with the palmitic acid-induced insulin resistance in HepG2 cells. At 10 µmol·L~(-1), compounds 4, 6, 7, and 9 can promote the glucose consumption of HepG2 cells with insulin resistance.

Paeoniflorin protects against cisplatin-induced acute kidney injury through targeting Hsp90AA1-Akt protein-protein interaction.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall has been used in Chinese Medicine for thousands of years, especially having anti-inflammatory, sedative, analgesic and other ethnic pharmacological effects. Moreover, Paeoniflorin is the main active ingredient of the Paeonia lactiflora Pall, and most are used in the treatment of inflammation-related autoimmune diseases. In recent years, studies have found that Paeoniflorin has a therapeutic effect on a variety of kidney diseases. AIM OF THE STUDY: Cisplatin (CIS) is limited in clinical use due to its serious side effects, such as renal toxicity, and there is no effective method for prevention. Paeoniflorin (Pae) is a natural polyphenol which has a protective effect against many kidney diseases. Therefore, our study is to explore the effect of Pae on CIS-induced AKI and the specific mechanism. MATERIALS AND METHODS: Firstly, CIS induced acute renal injury model was constructed in vivo and in vitro, and Pae was continuously injected intraperitoneally three days in advance, and then Cr, BUN and renal tissue PAS staining were detected to comprehensively evaluate the protective effect of Pae on CIS-induced AKI. We then combined Network Pharmacology with RNA-seq to investigate potential targets and signaling pathways. Finally, affinity between Pae and core targets was detected by molecular docking, CESTA and SPR, and related indicators were detected in vitro and in vivo. RESULTS: In this study, we first found that Pae significantly alleviated CIS-AKI in vivo and in vitro. Through network pharmacological analysis, molecular docking, CESTA and SPR experiments, we found that the target of Pae was Heat Shock Protein 90 Alpha Family Class A Member 1 (Hsp90AA1) which performs a crucial function in the stability of many client proteins including Akt. RNA-seq found that the KEGG enriched pathway was PI3K-Akt pathway with the most associated with the protective effect of Pae which is consistent with Network Pharmacology. GO analysis showed that the main biological processes of Pae against CIS-AKI include cellular regulation of inflammation and apoptosis. Immunoprecipitation further showed that pretreatment with Pae promoted the Hsp90AA1-Akt protein-protein Interactions (PPIs). Thereby, Pae accelerates the Hsp90AA1-Akt complex formation and leads to a significant activate in Akt, which in turn reduces apoptosis and inflammation. In addition, when Hsp90AA1 was knocked down, the protective effect of Pae did not continue. CONCLUSION: In summary, our study suggests that Pae attenuates cell apoptosis and inflammation in CIS-AKI by promoting Hsp90AA1-Akt PPIs. These data provide a scientific basis for the clinical search for drugs to prevent CIS-AKI.

Thermoacoustic Imaging-Guided Thermo-Chemotherapy for Hepatocellular Carcinoma Sensitized by a Microwave-Responsive Nitric Oxide Nanogenerator.

Imaging-guided percutaneous microwave thermotherapy has been regarded as an important alternative nonsurgical therapeutic strategy for hepatocellular carcinoma (HCC) that provides excellent local tumor control and favorable survival benefit. However, providing a high-resolution, real-time, and noninvasive imaging technique for intraoperative guidance and controlling postoperative residual tumor recurrence are urgent needs for the clinical setting. In this study, a cisplatin (CDDP)-loaded nanocapsule (NPs@CDDP) with microwave responsive property was prepared to simultaneously serve as a contrast agent of emerging thermoacoustic imaging and a sensitizing agent of microwave thermo-chemotherapy. Accompanying the enzymolysis in the tumor microenvironment, the NPs@CDDP responsively release l-arginine (l-Arg) and CDDP. l-Arg with excellent microwave-absorbing property allowed it to serve as a thermoacoustic imaging contrast agent for accurately delineating the tumor and remarkably increasing tumor temperature under ultralow power microwave irradiation. Apart from the chemotherapeutic effect, CDDP elevated the intracellular H2O2 level through cascade reactions and further accelerated the continuous transformation of l-Arg to nitric oxide (NO), which endowed the NPs@CDDP with NO-generation capability. Notably, the high concentration of intracellular NO was proved to aggravate lipid peroxidation and greatly improved the efficacy of microwave thermo-chemotherapy. Thereby, NPs@CDDP was expected to serve as a theranostic agent integrating the functions of tumor microenvironment-responsive drug delivery system, contrast agent of thermoacoustic imaging, thermal sensitizing agent, and NO nanogenerator, which was promising to provide a potential imaging-guided therapeutic strategy for HCC.

Screening of the Active Compounds against Neural Oxidative Damage from Ginseng Phloem Using UPLC-Q-Exactive-MS/MS Coupled with the Content-Effect Weighted Method.

The neuroprotective properties of ginsenosides have been found to reverse the neurological damage caused by oxidation in many neurodegenerative diseases. However, the distribution of ginsenosides in different tissues of the main root, which was regarded as the primary medicinal portion in clinical practice was different, the specific parts and specific components against neural oxidative damage were not clear. The present study aims to screen and determine the potential compounds in different parts of the main root in ginseng. Comparison of the protective effects in the main root, phloem and xylem of ginseng on hydrogen peroxide-induced cell death of SH-SY5Y neurons was investigated. UPLC-Q-Exactive-MS/MS was used to quickly and comprehensively characterize the chemical compositions of the active parts. Network pharmacology combined with a molecular docking approach was employed to virtually screen for disease-related targets and potential active compounds. By comparing the changes before and after Content-Effect weighting, the compounds with stronger anti-nerve oxidative damage activity were screened out more accurately. Finally, the activity of the selected monomer components was verified. The results suggested that the phloem of ginseng was the most effective part. There were 19 effective compounds and 14 core targets, and enriched signaling pathway and biological functions were predicted. After Content-Effect weighting, compounds Ginsenosides F1, Ginsenosides Rf, Ginsenosides Rg1 and Ginsenosides Rd were screened out as potential active compounds against neural oxidative damage. The activity verification study indicated that all four predicted ginsenosides were effective in protecting SH-SY5Y cells from oxidative injury. The four compounds can be further investigated as potential lead compounds for neurodegenerative diseases. This also provides a combined virtual and practical method for the simple and rapid screening of active ingredients in natural products.

Reactive Oxygen Species-Responsive Polypeptide Drug Delivery System Targeted Activated Hepatic Stellate Cells to Ameliorate Liver Fibrosis.

Hepatic fibrosis is a chronic liver disease that lacks effective pharmacotherapeutic treatments. As part of the disease's mechanism, hepatic stellate cells (HSCs) are activated by damage-related stimuli to secrete excessive extracellular matrix, leading to collagen deposition. Currently, the drug delivery system that targets HSCs in the treatment of liver fibrosis remains an urgent challenge due to the poor controllability of drug release. Since the level of reactive oxygen species (ROS) increases sharply in activated HSCs (aHSCs), we designed ROS-responsive micelles for the HSC-specific delivery of a traditional Chinese medicine, resveratrol (RES), for treatment of liver fibrosis. The micelles were prepared by the ROS-responsive amphiphilic block copolymer poly(l-methionine-block-Nε-trifluoro-acetyl-l-lysine) (PMK) and a PEG shell modified with a CRGD peptide insertion. The CRGD-targeted and ROS-responsive micelles (CRGD-PMK-MCs) could target aHSCs and control the release of RES under conditions of high intracellular ROS in aHSCs. The CRGD-PMK-MCs treatment specifically enhanced the targeted delivery of RES to aHSCs both in vitro and in vivo. In vitro experiments show that CRGD-PMK-MCs could significantly promote ROS consumption, reduce collagen accumulation, and avert activation of aHSCs. In vivo results demonstrate that CRGD-PMK-MCs could alleviate inflammatory infiltration, prevent fibrosis, and protect hepatocytes from damage in fibrotic mice. In conclusion, CRGD-PMK-MCs show great potential for targeted and ROS-responsive controlled drug release in the aHSCs of liver fibrosis.

Network Pharmacology and Molecular Docking-Based Investigation of Potential Targets of Astragalus membranaceus and Angelica sinensis Compound Acting on Spinal Cord Injury.

Background: Astragalus membranaceus (Huang-qi, AM) and Angelica sinensis (Dang-gui, AS) are common Chinese herbal medicines and have historically been used in spinal cord injury (SCI) therapies. However, the underlying molecular mechanisms of AM&AS remain little understood. The purpose of this research was to explore the bioactive components and the mechanisms of AM&AS in treating SCI according to network pharmacology and the molecular docking approach. Methods: AM&AS active ingredients were first searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Traditional Chinese Medicine Information Database (TCM-ID). Meanwhile, we collected relevant target genes of SCI through the GeneCards database, OMIM database, PharmGkb database, DurgBank database, and TDD database. By utilizing the STRING database, we constructed a network of protein-protein interactions (PPIs). In addition, we used R and STRING to perform GO and KEGG function enrichment analyses. Subsequently, AutoDock Vina was employed for a molecular docking study on the most active ingredients and most targeted molecules to validate the results of the network pharmacology analysis mentioned above. Result: The overall number of AM&AS active compounds identified was 22, while the number of SCI-related targets identified was 159. Then, the 4 key active ingredients were MOL000098 quercetin, MOL000422 kaempferol, MOL000354 isorhamnetin, and MOL000392 formononetin. A total of fourteen core targets were TP53, ESR1, MAPK1, MTC, HIF1A, HSP90AA1, FOS, MAPK14, STAT1, AKT1, EGFR, RELA, CCND1, and RB1. The KEGG enrichment analysis results indicated that lipid and atherosclerosis, PI3K-Akt signaling pathway, human cytomegalovirus infection, fluid shear stress, and atherosclerosis, etc., were enhanced with SCI development. Based on the analyses of docked molecules, four main active compounds had high affinity for the key targets. Conclusions: Altogether, it identified the mechanisms by which AM&AS was used for SCI treatment, namely, active ingredients, targets and signaling pathways. Consequently, further research into AM&AS treating SCI can be conducted on this scientific basis.

Bushen Huatan recipe for treatment of polycystic ovary syndrome: therapeutic mechanism based on network pharmacology and molecular docking / 南方医科大学学报

OBJECTIVE@#To explore the pharmacological mechanism of Bushen Huatan (BSHT) recipe in the treatment of polycystic ovary syndrome (PCOS).@*METHODS@#The active ingredients in the component drugs of the recipe were screened through TCMSP, and their potential targets were predicted by PubChem and Swiss target prediction. Genecards and OMIM were used to screen the therapeutic targets in the treatment of PCOS. The drug targets and disease targets were corrected using Uniprot, and the intersection targets were obtained. The protein-protein interaction (PPI) network was constructed using STRING, and the intersection targets were analyzed with CytoNCA to screen the core targets. DAVID was used for GO enrichment analysis and KEGG pathway enrichment analysis, and the core components and core targets were verified using AutoDock. Animal experiment was performed to verify the results using a female C57BL/6J mouse model of PCOS, treated daily with 1 mg/kg BSHT recipe granule for 35 days, and the ovarian expressions of the core targets and pathways were detected using Western blotting.@*RESULTS@#We identified a total of 125 potential active ingredients from the 14 component drugs in the recipe, 990 drug targets, 4759 PCOS targets and 434 intersection targets. The core active ingredients of the recipe included β -Sitosterol, kaempferol, and quercetin, whose core targets included PIK3CA, PIK3R1, APP, AKT1, and MAPK1. GO enrichment analysis highlighted such processes as drug reaction, negative regulation of apoptosis, and positive regulation of transcription from RNA polymerase Ⅱ promoter. The enriched KEGG pathways included primarily the cancer pathway and PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had strong binding ability with the core targets. In the animal experiment, BSHT recipe was shown to improve the symptoms, down-regulate the expressions of PI3K and Akt proteins and up-regulate MAPK1 expression in the ovary of mice with PCOS.@*CONCLUSION@#The therapeutic mechanism of BSHT recipe for PCOS involves multiple active ingredients, multiple therapeutic targets and multiple pathways.

Phosphorus emission from open burning of major crop residues in China.

Biomass burning has been recognized as an important primary source of atmospheric phosphorus (P), but the measurements of P from biomass burning particles are lacking. In this work, emission factors of different P forms, including total P (TP), total dissolved P (TDP), dissolved inorganic P (DIP) and dissolved organic P (DOP), in emission particles from four types of crop residues burning were measured in a number of chamber experiments. Based on the measured emission factors and the amount of crop residue burned, a high-resolution (0.25° × 0.25°) emission inventory of P for China during 2011-2015 was firstly developed. The emission factors of TP, DIP and DOP were 0.23, 0.06 and 0.13 g/kg, 0.57, 0.17 and 0.27 g/kg, 0.52, 0.15 and 0.27 g/kg, 0.43, 0.13 and 0.25 g/kg for wheat, corn, soybean and rice straw burning, respectively. The total emissions of TP, TDP, DIP, and DOP from the four types of crop straw open burning were 72.0 × 103 ± 6.7 × 103 Tons, 56.3 × 103 ± 5.5 × 103, 20.9 × 103 ± 2.0 × 103 and 35.4 × 104 ± 3.4 × 103 Tons, respectively. TDP dominated the TP fraction, indicating that biomass burning was the important source of bioavailable P. The high P emission areas were mainly distributed in the Northeast and North China Plain, where were the main grain production areas in China, while P emission in economically developed areas such as Beijing and Shanghai and western areas such as Tibet and Qinghai was lower. Affected by the harvesting periods of crops, high P emissions peaked in March, April, June and October. The results herein can provide a dataset for modeling research in calculating the contribution of biomass burning sources to atmospheric P; therefore reduce uncertainties in estimating atmospheric P deposition.

Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells.

Nicotinamide, the amide form of Vitamin B3, is a common nutrient supplement that plays important role in human fetal development. Nicotinamide has been widely used in clinical treatments, including the treatment of diseases during pregnancy. However, its impacts during embryogenesis have not been fully understood. In this study, we show that nicotinamide plays multiplex roles in mesoderm differentiation of human embryonic stem cells (hESCs). Nicotinamide promotes cardiomyocyte fate from mesoderm progenitor cells, and suppresses the emergence of other cell types. Independent of its functions in PARP and Sirtuin pathways, nicotinamide modulates differentiation through kinase inhibition. A KINOMEscan assay identifies 14 novel nicotinamide targets among 468 kinase candidates. We demonstrate that nicotinamide promotes cardiomyocyte differentiation through p38 MAP kinase inhibition. Furthermore, we show that nicotinamide enhances cardiomyocyte survival as a Rho-associated protein kinase (ROCK) inhibitor. This study reveals nicotinamide as a pleiotropic molecule that promotes the derivation and survival of cardiomyocytes, and it could become a useful tool for cardiomyocyte production for regenerative medicine. It also provides a theoretical foundation for physicians when nicotinamide is considered for treatments for pregnant women.

Berberine mitigates nonalcoholic hepatic steatosis by downregulating SIRT1-FoxO1-SREBP2 pathway for cholesterol synthesis.

OBJECTIVE: To investigate effects of berberine (BBR) on cholesterol synthesis in HepG2 cells with free fatty acid (FFA)-induced steatosis and to explore the underlying mechanisms. METHODS: A steatosis cell model was induced in HepG2 cell line fed with FFA (0.5 mmol/L, oleic acid:palmitic acid = 2:1), and then treated with three concentrations of BBR; cell viability was assessed with cell counting kit-8 assays. Lipid accumulation in cells was observed through oil red O staining and total cholesterol (TC) content was detected by TC assay. The effects of BBR on cholesterol synthesis mediators were assessed by Western blotting and quantitative polymerase chain reaction. In addition, both silent information regulator 1 (SIRT1) and forkhead box transcription factor O1 (FoxO1) inhibitors were employed for validation. RESULTS: FFA-induced steatosis was successfully established in HepG2 cells. Lipid accumulation and TC content in BBR groups were significantly lower (P < 0.05, P < 0.01), associated with significantly higher mRNA and protein levels of SIRT1(P < 0.05, P < 0.01), significantly lower sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy 3-methylglutaryl-CoA reductase levels (P < 0.05, P < 0.01), as well as higher Acetyl-FoxO1 protein level (P < 0.05, P < 0.01) compared to the FFA only group. Both SIRT1 inhibitor SIRT1-IN-1 and FoxO1 inhibitor AS1842856 blocked the BBR-mediated therapeutic effects. Immunofluorescence showed that the increased SIRT1 expression increased FoxO1 deacetylation, and promoted its nuclear translocation. CONCLUSION: BBR can mitigate FFA-induced steatosis in HepG2 cells by activating SIRT1-FoxO1-SREBP2 signal pathway. BBR may emerge as a potential drug candidate for treating nonalcoholic hepatic steatosis.

[Biochar addition improves soil phosphorus availability: A meta-analysis]. / ç”Ÿç‰©ç‚­æé«˜åœŸå£¤ç£·ç´ æœ‰æ•ˆæ€§çš„æ•´åˆåˆ†æž.

Biochar is a potential source for improving soil fertility and crop yield by enhancing phosphorus (P) availability. But the information on quantitative effect of biochar addition on soil P availability is still limited. To address this query, we conducted a meta-analysis with 507 data from 95 eligible literature. The results showed that irrespective of biochar characters (raw material, C:N ratio, pyrolysis temperature, application rate), soil characteristics (texture, pH, organic carbon content), and fertilizer application, biochar addition significantly improved soil available P content by 57.6%. Meanwhile, biochar addition promoted P utilization of crops. The response ratios of plant P concentration to biochar addition were generally lower than those of soil available P. The average response ratio of plant P concentration was 30.6%. The biochars, derived from livestock manure, low-temperature pyrolysis, with lower C:N ratio, alkaline, or higher application rate, were more effective to improve soil available P content and plant P concentration in sandy and loamy soils. For main enzymes involved in P cycle, biochar addition increased activity of alkaline phosphatase (2.8%) but decreased the acid phosphatase activity (17.8%). Overall, biochar addition positively affects soil available and plant P concentration, but has a minute effect on soil phosphatase. The improvement of soil P availability might mainly be ascribed to a great amount of active P fractions in biochar itself.

[Effects of fertilization and water addition on soil acid neutralizing capacity in an old-field grassland]. / æ–½è‚¥å’Œå¢žæ°´å¯¹å¼ƒè€•è‰åœ°åœŸå£¤é ¸ä¸­å’Œå®¹é‡çš„å½±å“.

Increasing nitrogen (N) deposition results in soil acidification in grasslands. Acid buffering capacity of soil is a critical index evaluating soil acidification, the response of which to N input is regulated by precipitation and concentration of other limiting elements. To explore the responses of soil acidification to N, phosphorus (P), and water inputs, we conducted a 13-year field experiment in an old-field grassland and calculated the acid buffering capacity (ABC) and acid neutralizing capacity (ANC) at the reference of pH=5.0 (ANCpH5.0) and 4.0 (ANCpH4.0), using quadratic curve fitting model. The results showed that, without water addition, single N addition or combined with P addition significantly decreased soil pH, ANCpH5.0 and ANCpH4.0, whereas single P addition had no significant effect on soil pH, ANCpH5.0 or ANCpH4.0. With water addition, the addition of N or combined with P decreased soil pH, ANCpH5.0 and ANCpH4.0, whereas P addition decreased soil pH, increased ANCpH4.0, without effect on ANCpH5.0. In contrast with treatments without water addition, water addition had positive effects on soil pH, ANCpH5.0 and ANCpH4.0. For soils with different initial soil pH values, it was better to select ANC rather than ABC as an index to evaluate soil anti-acidification capacity.

Analysis and Identification of Sesquiterpenes in Alpinia oxzphylla Miq Based on UPLC-Q-Orbitrap HRMS / 中草药

Objective: To establish a rapid and accurate analytical method for the identification of complex system of traditional Chinese medicine, and to systematically clarify the chemical composition of sesquiterpenes in Alpinia oxyphylla. Method: On the basis of optimizing the extraction process of sesquiterpenes, the accurate molecular weight and secondary fragment ions information of unknown compounds were captured by ultra-high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Compared with the relative retention time and mass spectrometry data of the reference substance, combined with relevant references and databases, the sesquiterpene unknown compounds in the fruits of A. oxyphylla were accurately and rapidly characterized. Results: A total of 24 sesquiterpenes were identified and classified into four categories according to their skeleton structure, including nine eudesmane-type, six cadinane-type, eight eremophilane-type, and one oplopanone-type. Conclusion: In this study, the established analytical method was used to realize the rapid and accurate identification of sesquiterpenes in the fruits of A. oxyphylla, which provided a theoretical basis for the research on the pharmacodynamic substance basis and quality control of the fruits of A. oxyphylla.

Unique phenolic constituent in Cimicifuga dahurica (Turcz.) Maxim. through Box-Behnken design and response surface methodology.

Cimicifuga dahurica (Turcz.) Maxim. exerts significant antioxidative due to its high phenolic constituent content. In this study, the extraction condition of the phenolic constituents and antioxidant effect was optimized by the Box-Behnken design and response surface methodology. Eleven main bioactive analytes of Cimicifuga dahurica (Turcz.) Maxim. were simultaneously quantified by high-performance capillary electrophoresis with diode-array detector to assess the effect of extraction technology. The optimal extraction parameters were determined as: the concentration of ethanol 56.21%, liquid/solid ratio 14.65:1, and extraction time 1.64 h for 2.67 times. According to the results, a maximal value of total phenolic acids (3.67 mg/g) was obtained. Meanwhile, the influence of different extraction technology on antioxidant activities were evaluated by 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonate), ferric reducing antioxidant power and hydroxyl radical scavenging method. The results presented here showed that the content of phenolic acid and antioxidant effect was much higher than the European Pharmacopoeia. Altogether, this method successfully applied response surface methodology to optimize the Cimicifuga dahurica (Turcz.) Maxim. extract with high antioxidant activities.

Water-Based Black Phosphorus Hybrid Nanosheets as a Moldable Platform for Wound Healing Applications.

Black phosphorus (BP) nanosheets with unique biocompatibility and superior optical performance have attracted enormous attention in material science. However, their instability and poor solution-processability severely limit their clinical applications. In this work, we demonstrate the use of silk fibroin (SF) as an exfoliating agent to produce thin-layer BP nanosheets with long-term stability and facile solution-processability. Presence of SF prevents rapid oxidation and degradation of the resultant BP nanosheets, enhancing their performance in physiological environment. The SF-modified BP nanosheets exhibit subtle solution-processability and are fabricated into various BP-based material formats. As superior photothermal agents, BP-based wound dressings effectively prevent bacterial infection and promote wound repair. Therefore, this work opens new avenues for unlocking current challenges of BP nanosheet applications for practical biomedical purposes.

Apelin in the hypothalamic paraventricular nucleus improves cardiac function in surgical trauma rats.

Apelin is a novel endogenous active peptide. The aim of this study is to investigate whether apelin in the paraventricular nucleus (PVN) can improve the cardiac function in rats subjected to thoracic surgery trauma, and whether it is involved in the protective effect of electro-acupuncture (EA). Sprague-Dawley rats were randomly divided into non-stressed group (control), thoracic surgical trauma stressed group (trauma) and bilateral Neiguan EA applied on thoracic surgical trauma stressed group (trauma + EA-PC 6). The mRNA expressions of apelin receptor (APJR) and apelin in the PVN were detected by real time-PCR. The exogenous apelin-13 (6 mmol/L, 0.1 µL) was microinjected into the rat PVN in the thoracic trauma group, and the effects of apelin-13 on the blood pressure (BP), heart rate (HR) and the discharge of rostral ventrolateral medulla (RVLM) neurons were observed through the simultaneous recording technology by polygraph. The results showed that the APJR mRNA expression was significantly decreased in the rats of trauma group as compared with that in the control group (P < 0.05), and a decline trend of apelin mRNA expression was also observed. EA application at bilateral Neiguan acupoints partially recovered the decline of APJR and apelin mRNA expression by the treatment of thoracic trauma. Both mean arterial pressure and HR in the thoracic surgical trauma group were significantly increased by the microinjection of exogenous apelin-13 into the PVN (P < 0.05), and the single-unit discharge rate of RVLM neurons also had an increasing trend. These results suggest that apelin in the PVN can improve the cardiac function of thoracic surgical trauma rats, and may be involved in the protective effects of EA.