Machine learning-guided the fabrication of nanozyme based on highly-stable violet phosphorene decorated with phosphorus-doped hierarchically porous carbon microsphere for portable intelligent sensing of mycophenolic acid in silage.

Violet phosphorene (VP) have been proved to be more stable than black phosphorene, but few reports for its application in electrochemical sensors. In this study, a highly-stable VP decorated with phosphorus-doped hierarchically porous carbon microsphere (PCM) with multiple enzyme-like activities as a nanozyme sensing platform for portable intelligent analysis of mycophenolic acid (MPA) in silage with machine learning (ML) assistance is successfully fabricated. The pore size distribution on the PCM surface is discussed using N2 adsorption tests, and morphological characterization indicates that the PCM is embedded in the layers of lamellar VP. The affinity of the VP-PCM nanozyme obtained under the guidance of the ML model reaches Km = 12.4 µmol/L for MPA. The VP-PCM/SPCE for the efficient detection of MPA exhibits high sensitivity, a wide detection range of 2.49 µmol/L - 71.14 µmol/L with a low limit of detection of 18.7 nmol/L. The proposed ML model with high prediction accuracy (R2 = 0.9999, MAPEP = 0.0081) assists the nanozyme sensor for intelligent and rapid quantification of MPA residues in corn silage and wheat silage with satisfactory recoveries of 93.33%-102.33%. The excellent biomimetic sensing properties of the VP-PCM nanozyme are driving the development of a novel MPA analysis strategy assisted by ML in the context of production requirements of livestock safety.

Analysis of Influencing Factors for Exercise Ventilation Efficiency of COPD Patients.

Dynamic pulmonary hyperinflation and abnormal air exchange are the primary causes of the exercise limitation of chronic obstructive pulmonary disease (COPD) patients. During exercise, COPD sufferers' lungs are dynamically hyperinflated. Increased inefficient ventilation reduces ventilation efficiency and causes a mismatch between ventilation volume and blood flow. The ventilatory equivalent for CO2 (VeqCO2) is a physiological parameter that can be measured using cardiopulmonary exercise testing. Therefore, the aim of this exploratory study was to perform cardiopulmonary exercise testing on people with COPD, investigate the impact of static pulmonary function on ventilation efficiency under the exercise state, and screen the predictive indicators of ventilation efficiency. Subject. The aim of this study was to look at the factors that influence the exercise ventilation efficiency of people with COPD. Method. A total of 76 people with COPD were recruited during the stable period. Age, gender, body height, body mass, and other basic information were recorded. The body mass index (BMI) was determined, and forced vital capacity (FVC), forced expiratory volume in one second (FEV1), residual volume/total lung capacity (RV/TLC), diffusing capacity of the lung for carbon monoxide (DLCO), and DLCO divided by the alveolar volume (DLCO/VA) were measured. The ventilatory equivalent for carbon dioxide (VE/VCO2) under the rest state (EqCO2rest), anaerobic threshold (EqCO2at), and maximum exercise state (EqCO2 max) were calculated to investigate the influencing factors for ventilation efficiency of people with COPD. Results. FEV1% was negatively correlated with EqCO2rest (r = -0.277, P value <0.05); FEV1/FVC % was negatively correlated with EqCO2rest and EqCO2at (r = -0.311, -0.287, P value <0.05); DLCO% was negatively correlated with EqCO2rest, EqCO2at, and EqCO2max (r = -0.408, -0.462, and -0.285, P value <0.05); DLCO/VA% was negatively correlated with EqCO2rest, EqCO2at, and EqCO2max (r = -0.390, -0.392, and -0.245, P value <0.05); RV/TLC was positively correlated with EqCO2rest and EqCO2at (r = 0.289, 0.258, P-value <0.05). The prediction equation from the multivariable regression analysis equation was Y = 40.04-0.075X (Y = EqCO2, X = DLCO/VA%). Conclusions. As the degree of ventilatory obstruction increased, the ventilation efficiency of the stable people with COPD under the exercise state showed a progressive decrease; the ventilation efficiency of the people with COPD decreased significantly under the maximum exercise state, and the ventilation capacity and diffusion capacity were the significant factors that affected the exercise ventilation efficiency. The diffusion function may predict the maximum ventilation efficiency and enable primary hospitals without exercise test equipment in developing countries to predict and screen patients at risk for current exercise based on limited information.

Study on Characteristics of Triterpenoids and Hepatoprotective Effects of Fruit Body of Stout Camphor Mushroom, Taiwanofungus camphoratus (Agaricomycetes), Cultivated with Apple-Wood.

Taiwanofungus camphoratus is a parasite medicinal fungus with significant hepatoprotective activity that grows in Cinnamomum camphora, a class II protected tree species in Taiwan. Currently, commercial cultivation of T. camphoratus is limited by the resources of C. camphora. To broaden the range of substrates, this study investigated the feasibility of using apple-wood as a substrate for T. camphoratus cultivation and examined the content of fruit body triterpenoids and liver-protective activity as quality indicators. The triterpenoids were determined by ultra-performance liquid chromatography-mass spectrometry and compared with T. camphoratus cultivated in C. camphora. The ICR mouse acute alcoholic liver injury model was used to explore the hepatoprotective effects of the apple-wood cultivated fungus. T. camphoratus grew on apple-wood medium within 7 months; a total of 62 fungal triterpenoid components were detected, including the seven characteristic triterpenoids. Only three were higher in T. camphoratus cultured on C. camphora. The medium-dose fungal extracts (150 mg/kg) produced significant protective effects against acute alcoholic liver injury in mice. These results indicate that apple-wood cultivation is a feasible method compared to C. camphora for commercial cultivation of T. camphoratus.

Cation/Anion Dual-Vacancy Pair Modulated Atomically-Thin Sex -Co3 S4 Nanosheets with Extremely High Water Oxidation Performance in Ultralow-Concentration Alkaline Solutions.

The density functional theory calculation results reveal that the adjacent defect concentration and electronic spin state can effectively activate the CoIII sites in the atomically thin nanosheets, facilitating the thermodynamic transformation of *O to *OOH, thus offering ultrahigh charge transfer properties and efficiently stabilizing the phase. This undoubtedly evidences that, for metal sulfides, the atom-scale cation/anion vacancy pair and surface electronic spin state can play a great role in enhancing the oxygen evolution reaction. Inspired by the theoretical prediction, interconnected selenium (Se) wired ultrathin Co3 S4 (Sex -Co3 S4 ) nanosheets with Co/S (Se) dual-vacancies (Se1.0 -Co3 S4 -VS/Se -VCo ) pairs are constructed by a simple approach. As an efficient sulfur host material, in an ultralow-concentration KOH solution (0.1 m), Se1.0 -Co3 S4 -VS/Se -VCo presents outstanding durability up to 165 h and a low overpotential of 289.5 mV at 10 mA cm-2 , which outperform the commercial Co3 S4 nanosheets (NSs) and RuO2 . Moreover, the turnover frequency of Se1.0 -Co3 S4 -VS/Se -VCo is 0.00965 s-1 at an overpotential of 0.39 V, which is 5.7 times that of Co3 S4 NSs, and 5.8 times that of commercial RuO2 . The finding offers a rational design strategy to create the multi-defect structure in catalysts toward high-efficiency water electrolysis.

16α-Bromoepiandrosterone as a new candidate for experimental diabetes-tuberculosis co-morbidity treatment.

Tuberculosis (TB) is the leading cause of death from a single bacterial infectious agent and is one of the most relevant issues of public health. Another pandemic disease is type II diabetes mellitus (T2D) that is estimated to affect half a billion people in the world. T2D is directly associated with obesity and a sedentary lifestyle and is frequently associated with immunosuppression. Immune dysfunction induced by hyperglycemia increases infection frequency and severity. Thus, in developing countries the T2D/TB co-morbidity is frequent and represents one of the most significant challenges for the health-care systems. Several immunoendocrine abnormalities are occurring during the chronic phase of both diseases, such as high extra-adrenal production of active glucocorticoids (GCs) by the activity of 11-ß-hydroxysteroid dehydrogenase type 1 (11-ßHSD1). 11-ßHSD1 catalyzes the conversion of inactive cortisone to active cortisol or corticosterone in lungs and liver, while 11-ß-hydroxysteroid dehydrogenase type 2 (11-ßHSD2) has the opposite effect. Active GCs have been related to insulin resistance and suppression of Th1 responses, which are deleterious factors in both T2D and TB. The anabolic adrenal hormone dehydroepiandrosterone (DHEA) exerts antagonistic effects on GC signaling in immune cells and metabolic tissues; however, its anabolic effects prohibit its use to treat immunoendocrine diseases. 16α-bromoepiandrosterone (BEA) is a water miscible synthetic sterol related to DHEA that lacks an anabolic effect while amplifying the immune and metabolic properties with important potential therapeutic uses. In this work, we compared the expression of 11-ßHSD1 and the therapeutic efficacy of BEA in diabetic mice infected with tuberculosis (TB) (T2D/TB) with respect to non-diabetic TB-infected mice (TB). T2D was induced by feeding mice with a high-fat diet and administering a single low-dose of streptozotocin. After 4 weeks of T2D establishment, mice were infected intratracheally with a high-dose of Mycobacterium tuberculosis strain H37Rv. Then, mice were treated with BEA three times a week by subcutaneous and intratracheal routes. Infection with TB increased the expression of 11-ßHSD1 and corticosterone in the lungs and liver of both T2D/TB and TB mice; however, T2D/TB mice developed a more severe lung disease than TB mice. In comparison with untreated animals, BEA decreased GC and 11-ßHSD1 expression while increasing 11-ßHSD2 expression. These molecular effects of BEA were associated with a reduction in hyperglycemia and liver steatosis, lower lung bacillary loads and pneumonia. These results uphold BEA as a promising effective therapy for the T2D/TB co-morbidity.

Research progress of correlation between multidrug resistance and transporters and traditional Chinese medicine intervention / 中国中药杂志

With the emergence of drug resistance in Western medicine, the repeated administration of clinical first-line drugs becomes more severe. There are many factors leading to multidrug resistance(MDR), so it is very difficult to solve the problem. Since traditional Chinese medicine(TCM) has been used in the field of MDR in recent years, the research on the transporter-associated drug resistance and intervention of TCM has gradually become a hot spot. Therefore, in order to further explore the relationships among drug resistance, transporters, and TCM intervention, we review the relevant research progress in recent years and comb the achievements and limitations of this research at present. In the end, we put forward the research direction of changing body's ADME through the host's transporters and gastrointestinal flora, which provides new ideas for future research.

[The miR-184 level in the seminal plasma exosome of male infertility patients and its clinical significance].

OBJECTIVE: To study the miR-184 level in the seminal plasma exosome of male infertility patients and its clinical significance. METHODS: Between 2015 and 2019, we collected 285 seminal plasma samples from 97 azoospermia (AS) and 96 asthenospermia (AZS) patients and 92 age-matched normal fertile controls in Jiangsu Provincial Hospital of Traditional Chinese Medicine, General Hospital of Eastern Theater Command and the First Hospital Affiliated to Wenzhou Medical University, identified the isolated seminal plasma exosomes by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot, and detected the miR-184 level in the seminal plasma exosomes by quantitative real-time PCR (qRT-PCR). We determined the clinical value of the miR-184 level and its correlation with semen parameters by multiple statistics, predicted the target genes and involved pathways of miR-184 by bioinformatic algorithms, and analyzed their relationship with male infertility. RESULTS: NTA, TEM and Western blot exhibited plenty of exosomes in the seminal plasma of the patients. The results of qRT-PCR showed that the miR-184 level in the seminal plasma exosome was dramatically decreased in the AS patients compared with that in the normal fertile controls (0.227 ［0.092, 0.790］ vs 0.650 ［0.408, 1.061］, P < 0.01), but increased in AZS males in comparison with that in the control group (1.176 ［0.661, 1.946］ vs 0.650 ［0.408, 1.061］, P < 0.01). The areas under the ROC curve (AUC) for differentiating the AS and AZS patients from the controls were 0.866 (95% CI: 0.815－0.916) and 0.724 (95% CI: 0.653－0.795), respectively, and that for differentiating the AS from the AZS group was 0.964 (95% CI: 0.943－0.985). The miR-184 level in the seminal plasma exosome of the AZS patients was correlated positively with the sperm count (r = 0.243, P = 0.017) but negatively with the percentage of progressively motile sperm (r = －0.407, P = 0.006). Bioinformatics analysis indicated that the downstream target genes of miR-184 were significantly enriched in the protein regulatory pathways closely related to male reproduction and spermatogenesis. CONCLUSIONS: The miR-184 level in the seminal plasma exosome of infertility patients is significantly different from that of normal fertile males, which may serve as a potential auxiliary marker for the diagnosis of and participate in the development and progression of male infertility.

Comprehensive ESI-Q TRAP-MS/MS based characterization of metabolome of two mango (Mangifera indica L) cultivars from China.

Polyphenols based bioactive compounds from vegetables and fruits are known for impressive antioxidant activity. Ingestion of these antioxidants may promote human health against cardiovascular diseases and cancer. Mango is a popular tropical fruit with special taste, high nutritional value and health-enhancing metabolites. The aim was to investigate the diversity of phytochemicals between two mango cultivars of china at three stages of fruit maturity. We used ESI-QTRAP-MS/MS approach to characterize comprehensively the metabolome of two mango cultivars named Hongguifei (HGF) and Tainong (TN). HPLC was used to quantify selected catechin based phenolic compounds. Moreover, real-time qPCR was used to study the expression profiles of two key genes (ANR and LAR) involved in proanthocyanidin biosynthesis from catechins and derivatives. A total of 651 metabolites were identified, which include at least 257 phenolic compounds. Higher number of metabolites were differentially modulated in peel as compared to pulp. Overall, the relative quantities of amino acids, carbohydrates, organic acids, and other metabolites were increased in the pulp of TN cultivar. While the contents of phenolic compounds were relatively higher in HGF cultivar. Moreover, HPLC based quantification of catechin and derivatives exhibited cultivar specific variations. The ANR and LAR genes exhibited an opposite expression profile in both cultivars. Current study is the first report of numerous metabolites including catechin-based derivatives in mango fruit. These findings open novel possibilities for the use of mango as a source of bioactive compounds.

[Therapeutic effect of cinnamaldehyde on ulcerative colitis in mice induced by dextran sulfate sodium with Candida albicans colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway].

To observe the efficacy of cinnamaldehyde on dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) with Can-dida albicans(Ca) colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway in mice. C57 BL/6 mice were randomly divided into normal group, DSS group, DSS+Ca group, cinnamaldehyde group and mesalazine group. Mice in DSS+Ca group were given Ca(1×10~8 CFU per mouse) through intragastrical administration for 4 consecutive days and then distilled water with 3.0% DSS for 7 consecutive days. In cinnamaldehyde group and mesalazine group, in addition to the induction method of the DSS+Ca group, mice were given 75 mg·kg~(-1) cinnamaldehyde and 200 mg·kg~(-1) mesalazine accompanied with 3.0% DSS for 7 consecutive days, respectively. Mice in normal group and DSS group were correspondingly administered with distilled water. The general conditions of the mice were observed daily, the diseased activity index(DAI) score was calculated, and fungal loads of feces were detected by plate method. The mice were sacrificed on day 12, colon length was measured, colon mucosa damage index(CMDI) score was calculated, and histopathological analysis was carried out by HE staining. Anti-saccharomces cerevisiae antibody(ASCA) and ß-1,3-glucan in serum, and TNF-α, IL-1ß, IL-6, IL-8, IL-10 in serum and colon tissue were detected by ELISA. The contents of ß-1,3-glucan and macrophage infiltration in colon tissues were examined by immunofluorescence staining. The protein expressions of dectin-1, TLR2, TLR4 and NF-κB were detected by Western blot and immunohistochemistry staining. The results showed that cinnamaldehyde could significantly improve the general conditions of UC mice with Ca colonization, decrease DAI and histopathological scores, reduce intestinal mucosal congestion, erosion and colon shortening, decrease Ca load in mouse feces and tissues, down-regulate the contents of ASCA and ß-1,3-glucan in serum, reduce the contents of TNF-α, IL-1ß, IL-6, IL-8 and increase IL-10 in serum and colon tissues, inhibit macrophages infiltration and down-regulate the protein expression of dectin-1, TLR2, TLR4 and NF-κB in colon tissue. These results suggested that cinnamaldehyde had a therapeutic effect on UC mice with Ca colonization, which might be related to the inhibition of Ca proliferation, the regulation of dectin-1/TLRs/NF-κB signaling pathways and the coordination of the balance between pro-inflammatory and anti-inflammatory factors.

Identification and quantification of Meiguihua oral solution using liquid chromatography combined with hybrid quadrupole-orbitrap and triple quadrupole mass spectrometers.

Meiguihua oral solution (MOS), a classical Chinese medicinal formula, was approved by the China Food and Drug Administration for production. However, the quality evaluation of MOS has not been reported. In this present study, qualitative and quantitative analysis of MOS were conducted by ultra high performance liquid chromatography coupled to quadrupole-orbitrap high resolution mass spectrometry (UHPLC-Q-orbitrap-HRMS) and high performance liquid chromatography-tri-quadrupole linear ion trap mass spectrometry (HPLC-tri-Q-LIT-MS). Totally 46 phenolic compounds (21 flavonoids and 25 tannins) were identified in the MOS, among them 14 polyphenols were not reported in raw plant materials of MOS. The simultaneous quantification of ten compounds including gallic acid, quercetin-3-O-sophoroside, ellagic acid, sophoraflavonoloside, hyperoside, isoquercitrin, avicularin, astragalin, quercitrin and juglanin, which were completed in 16 min in the negative electrospray ionization (ESI) mode under multiple reaction monitoring (MRM) method. Linearity was reached fine determination coefficient (r2 > 0.9995). Precisions, repeatability, stability (inter-day and intra-day), and recovery were validated and the relative standard deviations (RSD) were less than 2.9%, 4.7%, 3.6% and 1.79%, respectively. This result proved the high sensitivity and efficiency of the method. The quantitative and qualitative analysis of MOS would provide the substantial basis for further quality control and medicinal values.

Empirical Analysis and Modern Research of Zhenwutang / 中国实验方剂学杂志

Zhenwutang is the classic formula of Wenyang Lishui in " <italic>Treatise on Febrile Diseases</italic>" . It consists of five kinds of medicines, namely Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma Recens, Atractylodis Macrocephalae Rhizoma, Poria, Paeoniae Radix Alba or Paeoniae Radix Rubra. It has been included in the <italic>Catalogue of Ancient Classics</italic> (<italic>The First Batch</italic>) issued by the State Administration of Traditional Chinese Medicine in 2018.There are two articles in the " <italic>Treatise on Febrile Disease</italic>s" about the syndromes of Zhenwutang. On the basis of Article 82 of the Chapter of Taiyang disease, the Taiyang disease is demonstrated by sweating, but after that the patient still suffers from fever, epigastric throb, dizziness and shiver, this shall be treated with Zhenwutang. According to Article 316 of the chapter of Shaoyin disease, Shaoyin disease lasts for two or three days, until the fourth and fifth days, and is demonstrated by abdominal pain, difficult urination, severe pain in the limbs and diarrhea, the patient have a cough, diuresis, diarrhea and vomit, this shall be treated with Zhenwutang. The original texts discuss the basic pathogenesis is edema syndrome due to Yin and Yang deficiency, with symptoms of unfavorable urination, heavy limbs or edema, pale tongue, white moss and heavy pulse as dialectical points. In terms of the compatibility of prescriptions, usage and dosage, and the interpretation of prescriptions, this paper examines Zhenwutang syndromes in " Treatise on Febrilediseases" , summarizes the material basic research of Zhenwutang, and provides the basis for the quality control of its compound pharmacodynamics. This study summarizes the progress of pharmacological research for Zhenwutang in recent years, finds that Zhenwutang has many efficacies, such as cardiotonic, diuretic, lowering lipid, anti-oxidation, improving renal function and balancing of water and liquid metabolism, lists traditional Chinese medicine(TCM) syndromes treated with Zhenwutang, such as heart palpitations, edema, cough, abdominal pain, sipping, dizziness, and Western medicine diseases, like congestive heart failure, pulmonary heart disease, bronchial asthma, chronic colitis, cirrhosis, ascites, chronic glomerulonephritis, chronic renal failure, benign prostatic hyperplasia and Meniere's syndrome, expounds the principle of Zhenwutang for " treating different diseases with the same therapy" , in order to provide useful reference for the research and development and clinical application of Zhenwutang and more classic prescriptions.

Theory Analysis on Absorption of Exogenous Substances in Traditional Chinese Medicine / 中国实验方剂学杂志

The safety of traditional Chinese medicine is affected by many factors, and the influence of exogenous harmful substances has been concerned and become a hot spot in recent years, especially heavy metals, pesticide residues and some other harmful substances. In order to explore the effects of non-soil and non-pesticide treatment on residues of these two harmful substances, the heavy metals and agricultural residues of Lilii Bulbus were detected, and the correlation of the data was analyzed. In this experiment, heavy metals and pesticide residues of Scrophulariae Radix were detected, and correlation analysis was conducted for their data. The mechanism of transport phase was interpreted with statistical moment similarity tool of total fingerprint by supramolecular chemistry theory. A large number of experimental data in this paper showed that heavy metals and pesticide contents in Lilii Bulbus basaltifolia had a positive correlation, which was closely related to supramolecular phenomena. Moreover, the similarity of fingerprints between Lilii Bulbus and Scrophulariae Radix suggested that Lilii Bulbus and Scrophulariae Radixa had a high selectivity in absorption of agricultural residues, which proved that the absorption of pesticides in Lilii Bulbus and Scrophulariae Radix from different habitats had the function of supramolecular imprinting template. It was considered that medicinal plant was a giant complex supramolecule with various levels of " imprinted template" . Heavy metals and agricultural residues were also involved in plant growth, forming an " imprinted template" for the formation of supramolecules between agricultural residues and heavy metals. After heavy metals and agricultural residues formed supramolecules, their liposolubility and permeability changed in varying degrees, and their transport in medicinal plants was promoted. Finally, the heavy metal supramolecules of pesticides were absorbed, distributed, aggregated and accumulated in plants. The purpose of the study was to reveal the mechanism of heavy metal and pesticide supramolecule transport, provide a new direction for the treatment of heavy metals and pesticide residues, and ensure the safety of traditional Chinese medicine.

[Morphological characteristics identification and molecular DNA barcoding analysis of Hippocampus spinosissimus].

The combination of morphological characteristics and DNA barcodes was used to a systematic study of Hippocampus spinosissimus,laying the foundation for rapid and accurate identification for the medical seahorse species. According to the reported literature and observation on seahorse samples,the typical characteristics of the H. spinosissimus include highly developed spiny,much short nose,single or double cheeks and strongly developed spines bordering pouch. Genomic DNAs of H. spinosissimus and other related seahorse species were extracted using the TIANamp Marine Animals DNA Kit. The COⅠ and ATP6 genes were amplified and sequenced in both directions. After the verification by Blast,the GC content,intraspecific and interspecific genetic distance,and the Neighbor joining( NJ) phylogenetic trees were analyzed by MEGA 7. The lengths of the COⅠ and ATP6 genes were 649 bp and 602-603 bp,respectively,with the average GC content of 39. 96% and 35. 37%. The maximum intraspecific genetic distances in H. spinosissimus based on COⅠ and ATP were both far less than the minimum interspecific genetic distance between H. spinosissimus and other seahorses,suggesting a significant barcoding gap. NJ analysis results of COⅠ and ATP6 exhibited that all H. spinosissimus species clustered together,indicating that the two DNA barcode could identify H. spinosissimus from other seahorses accurately and quickly. In addition,H. spinosissimus shared a close genetic relationship between H. kelloggi according to the NJ tree. Furthermore,there exits three stable subgroup structure of H. spinosissimus,indicating that COⅠ and ATP6 barcodes could be applied the indicator for the geographical ecology research of H. spinosissimus. The results obtained the typical morphological and molecular identification characteristics of H. spinosissimus,which played central roles for the development of species identification. This study provides an important basis data for expanding the medical seahorse resources and ensuring the safety of clinical medicine.

Phosphorene nanocomposite with high environmental stability and antifouling capability for simultaneous sensing of clenbuterol and ractopamine.

A series of phosphorene (BP) nanocomposites was prepared to realize simultaneous electrochemical determination of clenbuterol (CLB) and ractopamine (RAC). CLB and RAC are the most commonly used ß-agonists in animal-derived food. The BP nanohybrid was obtained by co-decoration with both mono(6-mercapto-6-deoxy)-ß-cyclodextrin and poly(3,4-ethylenedioxythiophene) nanoparticles. It displays high stability, antifouling capability, a large electrochemical active surface and good electrochemical response. The electrochemical assisted antifouling strategy was selected by further eliminating the fouling of the electrode surface using continuous cyclic voltammetry. The electrode was employed for electrochemical sensing of CLB and RAC at typical peak voltages of 0.8 and 1.0 V (vs. SCE). Responses are linear in the 0.3-90 µM concentration range for CLB, and from 0.3 to 9.4 µM for RAC under optimal conditions. The limit of detection are 0.14 and 0.12 µM, respectively. The sensor was employed for simultaneous determination of CLB and RAC in (spiked) beef, feed and bovine serum samples with acceptable recoveries. Graphical abstractAn electrochemically assisted anti-fouling method for simultaneous voltammetric nanosensing of clenbuterol (CLB) and ractopamine (RAC) in edible cattle product samples using high-stable and anti-foul phosphorene (BP) co-decorated with mono(6-mercapto-6-deoxy)-ß-cyclodextrin (S-ß-CD) and poly(3,4-ethylenedioxythiophene) (PEDOTNPs).

[Current status and future prospect of pharmacotherapy for pancreatic cancer].

Pancreatic cancer is the most common digestive tract tumor with an increasing incidence in recent years. The poor prognosis of pancreatic cancer is mainly because of the inability of detecting tumor at an early stage,its high potential for early dissemination,and its relatively poor sensitivity to chemotherapy. Most patients have lost the opportunity for surgery when they are diagnosed,which resulted in an urgent need for the development of more effective and safe therapies for pancreatic cancer. However,the current clinical cancer chemotherapy based on gemcitabine leads to poor prognosis in pancreatic patients. With the continuous research on the biological and cellular signaling pathways of pancreatic cancer,there have emerged a great many of novel agents,including new chemotherapeutic,targetable and immune-modulatory drugs,and some drugs have achieved encouraging results. Furthermore,as an alternative and supplementary method,traditional Chinese medicine has shown good application prospects in the field of pancreatic cancer treatment. This article reviews the current status of drug therapy for pancreatic cancer,summarizes the strength and weakness of existing therapeutic drugs in the application process,gives prospects of possible breakthroughs for the pharmacotherapy in the future,and provides certain new ideas and lessons for subsequent drug development.

Interpretation of Prescription and Syndrome of Yangjing Zhongyu Tang and Its Modern Research Progress / 中国实验方剂学杂志

Yangjing Zhongyu Tang, from FU Qing-zhu Nvke, is a famous classical formula of clinical value for treating blood deficiency syndrome of female infertility in the Qing dynasty. The prescription seems plain, but it is rigorous and effective with high research value. In this paper, the ancient books and modern documents of Yangjing Zhongyu Tang were analyzed from the aspects of traceability of Chinese materia medica in the formula, pharmacological research, clinical research, etc. It could be concluded that the pharmacological studies of this formula were mostly to investigate the mechanism and efficacy of its treatment for infertility, but there was a lack of comprehensive interpretation of the structure, function and principle of pharmacodynamic substance in this formula. In this paper, combined with the contents of supramolecular imprinting template and network pharmacology, the new direction of pharmacological research of Chinese medicine compound was put forward. Quality control of Yangjing Zhongyu Tang mostly based on small molecule compounds, so it was suggested to break the inherent thinking, and increase the detection of macromolecule compounds and supramolecular of Chinese materia medica. The druggability of this formula involved in the preliminary study of decoctions, plasters and granules. Considering the quality stability of Chinese materia medica in the formula and the scientificity of druggability of this formula, the compatibility principle of traditional Chinese medicine (TCM) and modern supramolecular chemistry theory could be combined to study the change law of druggability of TCM before and after compatibility, so as to provide new reference materials for the follow-up clinical application and development of Yangjing Zhongyu Tang.

[Inhibitory effect and mechanism of platycodin D combined with imatinib on K562/R].

Platycodin D(PD) has a significantly inhibitory effect on multiple malignant tumors, and can inhibit the proliferation of leukemia cells K562 and induce apoptosis. However, its effect in improving the sensitivity of drug-resistant cells to imatinib and their molecular mechanism remained unclear. To investigate the effect and mechanism of PD alone or combined with imatinib (IM) in inhibiting CML imatinib resistant cell line K562/R, the cell proliferation was examined by CCK8 assay to reveal the effect of PD on the inhibitory function of imatinib. Cell apoptosis was detected by Annexin V-FITC/PI double staining. Protein expressions of cleaved caspase-3, cleaved caspase-9, PARP, cleaved PARP, Bcr/abl, p-AKT and p-mTOR were detected by Western blot. The results showed that the inhibitory effect of PD combined with imatinib on the proliferation and apoptosis of K562/R cells was significantly higher than that of the control group and the single drug group. Protein expressions of cleaved caspase-3, cleaved caspase-9 and cleaved PARP were significantly up-regulated in the combination group, and protein expressions of PARP, Bcr/abl, p-AKT and p-mTOR were down-regulated. The results indicated that PD increased the sensitivity of drug-resistant cells to imatinib, and the inhibitory effect of PD combined with imatinib was significantly better than the single drug on cell proliferation, induction of apoptosis, inhibition of Bcr/abl protein and PI3K/AKT/mTOR signaling pathway.

Development of Plant Metabolomics Analytical Approach Based on Liquid Chromatography Tandem Mass Spectrometry in Artemisia rupestris L / 分析化学

Due to the diversity and complexity, the change of chemical components in medicinal plant according to the time, cultivated varieties or ecological condition is difficult to recognize using traditional phytochemistry method. In order to analyze the pharmacodynamics material basis in Uighur medicinal plant Artemisia rupestris L. in an effective and comprehensive way, a plant metabolomics approach was established based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). This study firstly focused on the effect of extraction solvents,redissolve solvents and ultrasonic time on the untargeted metabolomics, then the optimal preparation condition was selected according to metabolites coverage. After methodology validation, the approach was applied to acquire metabolic information in root, stem, branchlet, leaf and flower of Artemisia rupestris L. The results showed that the metabolome in flower was obviously different with the other organs. Coupling with multivariate statistical analysis, a batch of differential metabolites were picked out, in which 61 flavonoids, 97 rupestonic acid derivatives, 7 chlorogenic acids and 15 other compounds were primarily recognized according to the characteristic fragmentation rules of specific structure type and database retrieval. Additionally,the distribution characteristics of the above 180 differential metabolites was illustrated by cluster heat map. In conclusion,this study provided important information about the rational utilization of effective parts from Artemisia rupestris L.,and offered a novel strategy for quality control,variety improvement and reasonable development of medicinal plants.

Ginkgo biloba exocarp extracts induces autophagy in Lewis lung cancer cells involving AMPK / mTOR / p70S6k signaling pathway.

OBJECTIVES: Ginkgo biloba L. is called a living fossil plant, and could be used for the treatment of cancer thousands of years ago in China. The extracts prepared from the Ginkgo biloba exocarp (Ginkgo biloba exocarp extracts, GBEE) has a significant anti-cancer effect. Autophagy plays an important role in the occurrence and development of cancer as programmed cell death (PCD) type II. Thus it would be interesting to study the effects and mechanisms of GBEE inducing autophagy in Lewis lung cancer (LLC) cells. METHODS: MTT method was used to detect the inhibitory effect of GBEE on LLC cells. Monodansylcadaverine (MDC) staining method was applied to observe the formation of acidic vacuoles in cells. The ultrastructure of LLC cells was observed using transmission electron microscope (TEM) to confirm the formation of autophagosomes. Quantify reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the mRNA levels of Beclin1 and Atg5. Western Blot was used to detect the protein levels of Beclin1, Atg5, LC3I/II, p-AMPK, AMPK, p-mTOR, mTOR, p-p70S6k and p70S6K in LLC cells. RESULTS: GBEE (5-160µg/mL) inhibited the proliferation of LLC cells in vitro with the half maximal inhibitory concentration (IC50) value of 161.26µg/mL. The formation and activation of acidic vacuoleswere increased by the action of GBEE (10, 20 and 40µg/mL) on LLC cells. The autophagosomes were also increased. Meanwhile, it up-regulated both the mRNA and protein levels of Beclin1 and Atg5. The ratio of LC3-I/LC3-II protein was down-regulated. In addition, the protein level of p-AMPK was increased, and the p-mTOR and p-p70S6K was decreased. But the AMPK, mTOR and p70S6K proteins were not significantly changed. CONCLUSIONS: The inhibitory effect of GBEE on LLC is associate with inducing autophagy in LLC cells, which may be closely relevant to the regulation of AMPK/mTOR/p70S6k signaling pathways.

[Progress of regulation of leukemia stem cells of chronic myeloid leukemia by autophagy].

Leukemia stem cells (LSC) that were found in chronic myeloid leukemia (CML) responsible for the abnormal proliferation with the potential of self-renewal and multi-directional differentiation are involved in the pathophysiological process for drug resistance and relapse of CML. Autophagy, a conservative lysosomal degradation process that mediates cell degradation and recycling process, plays crucial roles in maintaining the homeostasis and function of intracellular environment. Recent studies suggested that autophagy is involved in the regulation of LSC differentiation and also closely related to the chemo-sensitivity of CML. In this review, we focused on the role of autophagy on chemotherapy sensitivity of CML as well as the leukemia stem cell function for the development of new anti-leukemia drugs.