Natural products with diverse structures and significant biological activities were important source of lead compounds, and have played a key role in the innovative drug development. Recently, China has been in the prior position in discovering of structurally diverse active natural products from natural medicines. In 2018, a series of natural products with novel structures and significant biological activities have been isolated and studied by scholars from China, and 73 molecules with novel carbon frameworks have been selected as "Hot of The Press" by Nat Prod Rep Journal. In this review, the original, structures and biological activities of 123 compounds of natural products research field in 2018 were briefly described, which was aimed to exhibit the highlights of natural products research from China in past year.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) infection remains a major public health problem of global concern, largely due to antibiotics resistance, persistence and immune evasion. Sphingolipid bioactive molecules are involved in several important pathophysiological processes. Sphingosine-1-phosphate is a key product of sphingolipid metabolism, and can play a role in two manners:autocrine and/or paracrine. Sphingosine-1-phosphate regulates T cells and a variety of antigen-presenting cells during M. tuberculosis infection, promotes antigen processing and expression in monocytes, is involved in the maturation of phagolysosome, regulates Ca²⁺ homeostasis, participates in the autophagy of macrophages, inhibits the survival and proliferation of M. tuberculosis within host cells, and effectively reduces the necrosis of the mouse lungs infected by M. tuberculosis. Injection of 20 nmol per mouse sphingosine-1-phosphate inhibited up to 47% of mycobacterial growth in the lung and spleen of mice infected by M. tuberculosis. In this paper, sphingosine-1-phosphate, its receptors and regulatory network were reviewed, and the specific mechanism of sphingosine-1-phosphate inhibiting the survival of M. tuberculosis-infected host cells was elaborated. This will provide novel insights into the new targets for tuberculosis prevention and treatment.

Diabetic kidney disease (DKD) is one of the most serious microvascular complications in diabetic patients, and is the leading cause of end-stage renal disease. The interaction between metabolic and hemodynamic factors leads to activation of the common pathways of diabetic kidney injury. Studies have shown that salvianolic acid can alleviate renal fibrosis and renal injury caused by diabetes by regulating renal tubular interstitial activator A, transforming growth factor-β1 and monocyte chemokine protein-1. It can also participate in the reconstruction of the glomerular extracellular matrix by affecting the expression of protein kinase ERK1/2 protein, which serves a protective effect on diabetic kidneys. Tanshinone can inhibit oxidative stress mediated glucose-induced kidney injury, inhibit the expression of protein tyrosine phosphatase 1B (PTP1B) activity, and improve the secretion function of beta cells in type 2 diabetes mellitus. Interstitial fibrosis in diabetic nephropathy can be alleviated by blocking TGF-β/Smad, NF-κB and Wnt/β-catenin signaling pathway. It has been suggested that salvianolic acid and salvianone are excellent candidates for prevention and treatment of diabetic nephropathy. We provide here the scientific basis for in-depth research and development of salvianolic acid and salvianone into drugs.

Lung cancer ranks the first in the mortality rate among all cancers, and non-small cell lung carcinoma (NSCLC) accounts for about 80% of the incidence of lung cancer. In recent years, the drugs targeting specific molecules have been developed rapidly. The epidermal growth factor receptor-tyrosine kinase inhibitors (EGFRTKIs) have achieved good results in the treatment of patients with NSCLC. Currently, there are three generations of EGFR-TKIs, and the treatment outcome of these drugs surpasses traditional chemotherapies. However, the problems of acquired resistance remains in the course of treatment. In this review, research progress of the mechanisms of acquired resistance is divided into two parts:EGFR-dependent pathway and EGFR-independent pathway. The EGFR-dependent pathway mainly includes EGFR gene mutations, whereas the EGFR-independent pathways include HER2 amplification, BIM deletion, activation of HGF/c-Met pathway, activation of IGF1R, RAS mutation, PTEN deletion, epithelial-mesenchymal transition, PUMA loss, and high levels of expression of VEGF or IL-6. These interconnected mechanisms are linked with acquired resistance to EGFR-TKIs in NSCLC.

Cellular energy metabolism disorder caused by dysfunction of nutrient utilization and mitochondrial damage contributes to a variety of diseases, including neurodegenerative diseases, cancer, metabolic diseases, and cardiovascular diseases. Understanding the effects of energy metabolism on diseases will help to improve our knowledge about disease etiology and may serve to develop strategies to delay disease progress. There are many compounds developed for targeting energy metabolism disorders, such as small molecules targeting the 18 kDa transporter (TSPO) for treatment of Alzheimer's disease, glucagon-like peptide-1 analogues for treatment of Parkinson's disease, inhibitors of glucose transporter 1 (GLUT1) and lactate dehydrogenase A for treatment of tumors, the fibroblast growth factors based treatment for type 2 diabetes (T2D), selective ligands of peroxisome proliferator-activated receptor (PPAR)-β/δ for treatment of cardiovascular diseases. We review here the abnormal energy metabolism of common energy metabolism disorder-related diseases, summarize the potential targets that may be used for new drug discovery, and the strategies for alleviating the disease process by improving energy metabolism.

Aging is a normal physiological process involving coaction of many factors. The anti-aging effects of natural products have been studied by many domestic and international scholars, but not far enough, which still needed to be explored. Flavonoids, as natural products, have a variety of pharmacological activities and present in many traditional Chinese medicines. In recent years, research results indicate that flavonoids can delay the aging process of the nervous, immune, and reproductive systems, and the liver, skin and other tissues. The anti-aging effects of flavonoids have attracted more and more attention. Therefore, development of anti-aging drugs from flavonoids is of great significance to improve the quality of life for the elderly and slow the process of aging. However, the mechanism of the anti-aging effect of flavonoids remains unknown at present. This review will discuss the anti-aging effect and mechanisms of flavonoids in traditional Chinese medicine from the aspects of cellular signaling pathways and metabolic pathways based on the modern theories of aging.

Antiretroviral therapy has been used for treating AIDS with 31 single-target anti-HIV drugs currently on market. Searching for safe and effective of novel anti-HIV drugs remains a challenge worldwide. Multi-targets single-structure compounds referred to as designed multiple ligands (DMLs) have become a hot topic of producing anti-HIV drugs recently due to reduction in the likelihood of drug resistance, simplified dosing and improved patient adherence. Integrase (IN) and ribonuclease H (RNase H) are two indispensable enzymes in HIV republication, therefore are two important targets for developing anti-HIV drugs. Recently, diverse dual inhibitors of HIV IN and RNase H (IN/RNase H) have been developed via rational drug design and screening. This review summarizes the advances in chemically synthesized dual inhibitors of HIV IN/RNase H to provide the information for developing multi-targets anti-HIV drugs.

Utilization of traditional Chinese medicine (TCM) resources for pharmaceutical development is an important part of modernization of TCM. The classical TCM prescriptions provide an important insight for developing new drugs. Based on the advantages of local TCM resources, focusing on the key scientific problems in the quality evaluation of medicinal materials and the study of classical prescriptions, this research group takes the quality evaluation of medicinal materials as the starting point. Metabolomics serves as a technical means of "quality evaluation of TCM, to support scientific connotation of classical prescriptions and development of new drugs from TCM. Using Radix Bupleurum as an example, this paper systematically and thoroughly expounds the above research ideas and strategies from the aspects:quality evaluation of medicinal materials, basic research of Xiaoyansan, and research and development of new anti-depressants. This provides the scientific basis for the modernization of TCM.

This study was designed to explore the antipyretic mechanism of Pueraria radix. The method of network pharmacology was used to determine the known ingredients corresponding to Pueraria radix, predict the drug-related gene/protein targets, and analyze the interplay between key ingredients and targets. Biological Information Annotation Databases (DAVID) was used to enrich the biological processes and pathways. The result of network analysis was validated by molecular docking. It was found that 49 active ingredients of Pueraria radix not only regulate 21 targets (e.g. PTGS2, EGFR), but also affect 11 biological processes (e.g. oxidation-reduction process, prostaglandin synthesis, positive regulation of fever generation and inflammatory response) and 7 metabolic pathways (arachidonic acid metabolism, serotonergic synapse and HIF-1, et al). Molecular docking results showed that more than 65% of the active ingredients could be well docked with key targets, and the relevant literatures indicated that the active components could inhibit the expression of PTGS2, which means the result has a high reliability. These results indicated that Pueraria radix may carry its pyretic action via a "multi-ingredients-multitargets-multi-pathways" mode, which provides a scientific basis for further research and drug development.

This study was designed to investigate the inhibitory effect and mechanism of neferine (Nef) on invasion and metastasis of nasopharyngeal carcinoma cells (NPC). The viability of CNE-1 and 5-8F cells was detected by CCK-8 assay after treatment with different concentrations of Nef. The effects of Nef on cell migration and invasion were detected by the scratch test and Transwell assay. Western blot analysis was used to detect the effects of Nef on levels of epithelial-mesenchymal transition (EMT)-associated proteins and transcription factors. The differentially expressed gene profiles between control group and Nef group were analyzed by microRNA microarray, combined with bioinformation analysis. It was observed that 30 μmol·L^-1 Nef had no significant effect on the viability of CNE-1 and 5-8F cells. Western blot assay showed that the expression level of neurotroponin cadherin (N-cadherin) and vimentin decreased after treatment with Nef, while the expression of epithelial cadherin(E-cadherin) increased. The expression of transcription factors including Twist, Snail, and Slug exhibited no significant difference. Results of the microRNA microarray suggest that 10 microRNAs showed significant differences when compared with the control group. Bioinformatics analysis showed that hsa-let-7c-5p and hsamicroRNA-423-5p targeted the same downstream genes:small integral membrane protein 3 (SMIM3) and nerve growth factor (NGF). Overexpression of hsa-let-7c-5p and hsa-miR-423-5p promoted the invasion and migration ability of 5-8F cells and decreased the expression of SMIM3 and NGF. The results from this study suggest that Nef may inhibit the invasion and metastasis of NPC cells by inhibiting the expression of hsa-let-7c-5p and hsamiR-423-5p followed by the upregulation of SMIM3 and NGF; thus, regulating the expression of EMT-associated proteins. Our data have provided experimental evidence for the inhibition of tumor invasion and metastasis by Nef.

This study aimed to explore the anti-tumor activity and mechanisms of action of isorhamnetin, a compound isolated from Astragalus membranaceus, in combination with sorafenib for treatment of renal cell carcinoma (RCC). The anti-tumor activity of isorhamnetin in combination with sorafenib was detected by MTT assay with cells in culture or Renca xenograft model in mice. Western blot was used to study the mechanisms of isorhamnetin in combination with sorafenib. Lymphocyte proliferation assay was also used to investigate the effects of the two drugs in combination. The results indicated that isorhamnetin inhibited the proliferation of RCC cells, with IC₅₀ for A498, 786-O and Renca cell lines with being 31.7, 28.8 and 106.0 μmol·L^-1, respectively. Isorhamnetin in combination with sorafenib improved the anti-lymphocyte proliferation activity of sorafenib with the IC₅₀ down to 12.0 μmol·L^-1. Isorhamnetin inhibited the growth of RCC in mice slightly with the inhibition efficiency at 26.9%. With 50.0 mg·kg^-1 isorhamnetin in combination with 20.0 mg·kg^-1 sorafenib, the anti-tumor activity of sorafenib was enhanced, with inhibition of growth rate increased to 60.7%. Meanwhile, isorhamnetin in combination with sorafenib could promote the lymphocytes proliferation in Renca xenograft model. Western blot results showed that combination of isorhamnetin and sorafenib could inhibit c-Raf/MEK/ERK and AKT/mTOR signaling pathways. In conclusion, the combination of isorhamnetin with sorafenib could increase the anti-tumor activity of sorafenib in RCC in vitro and in vivo. The mechanisms may be related to the inhibition of c-Raf/MEK/ERK and AKT/mTOR signaling pathways. Procedures for animal study were performed with approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College.

This research is aimed to investigate the effect of ampelopsin on apoptosis and migration of human hepatoma SMMC-7721 cells and explore the molecular mechanism. SMMC-7721 cells were pretreated with different doses of ampelopsin and cells proliferation was detected by CCK8 kit. Cell morphology was observed under an inverted microscope. Nuclear morphology was detected by DAPI staining. Apoptotic rate was detected by Annexin V-FITC/PI flow cytometry. Migration and invasion were detected by Transwell and scratch healing test. Western blotting was used to detect cleavage of poly ADP-ribose polymerase (PARP), expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), E-cadherin, and N-cadherin, and phosphorylation of ERK, P38 and JNK in MAPKs pathway. Our results showed that ampelopsin significantly inhibited proliferation and induced apoptosis of SMMC-7721 cells, with half inhibition dose (IC₅₀) for 24 h was 38.98 μg·mL^-1. With 50 μg·mL^-1 ampelopsin treatment, typical apoptotic morphological changes occurred, such as cell detachment, shrinkage and nuclear condensation. Apoptotic rate increased from 15% to 55.1%, with PARP cleavage significantly increased. In addition, treatment of ampelopsin reduced scratch healing of cells and transmembrane cells number. The expression levels of MMP-2 and MMP-9 were decreased. Further analysis of EMT-related proteins showed that after ampelopsin treatment, E-cadherin was up-regulated and N-cadherin was down-regulated. During ampelopsin treatment, ERK reached its peak of activation after 1 h, while the maximum activation time of JNK was 12 h. Meanwhile, P38 was activated within 4 h, with the highest point at 2 h. But after 4 h, ampelopsin inhibited phosphorylation of P38. These results indicated that ampelopsin induced apoptosis and reduced migration through activating MAPKs pathway and reversing EMT process in SMMC-7721 cells. This work provides a mechanistic basis for utilizing ampelopsin for anti-hepatocarcinoma treatment.

We studied the effect of aqueous extract from Huang qi on gene expression profile of doxorubicin induced nephropathy in rats, and explored the molecular mechanism of the intervention. The gene expression profiles of control group, model group and aqueous extract from Huang qi group were detected by using transcriptome sequencing technique. The differentially expressed genes (DEGs) were screened by STEM trend analysis software. GO function enrichment and KEGG pathway analysis were performed for DEGs, and the gene expression level was verified by real-time fluorescence quantitative PCR (RT-qPCR). The results showed that, compared with the control group, 432 DEGs were obtained in doxorubicin nephropathy model group; compared with the model group, 811 DEGs were obtained due to aqueous extract of Huang qi. The results of GO function enrichment and KEGG enrichment analysis indicated that PI3K-AKT pathway (Col6a6, Nr4a1, Sgk1, Gng7) and lipid metabolism-related genes (Cpt1b, Pcsk9, Abca1, Ascm5) were the key pathways and genes in the treatment of doxorubicin induced nephropathy by aqueous extract from Huang qi, which played a protective role in kidney. In conclusion, the molecular mechanism of aqueous extract from Huang qi in protection against doxorubicin induced nephropathy rats is closely related to apoptosis-related genes and lipid metabolism-related genes, suggesting for the need of follow-up study for key gene validation and mechanism of action of aqueous extract from Huang qi for prevention of doxorubicin induced nephropathy.

About 15%-20% of drug-induced liver injury (DILI) will progress to chronic manifestation (CH-DILI), which sometimes advances rapidly to liver cirrhosis (LC-DILI) within 0.5-1 year with deteriorative clinical prognosis. Therefore, it is important to find a non-invasive diagnosis for early detection of liver cirrhosis. In this study, the metabolomic profiles revealed significant differences in the metabolites from the plasma of LC-DILI versus CH-DILI. We found 35 differential metabolites through principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Through pathway enrichment analysis, some up-regulated metabolic pathways reflected impaired liver functions such as bile acid, lipid synthesis and decomposition during cirrhosis. Five biomarkers were found to exhibit effective diagnosis value (AUC > 0.6), including phosphatidylcholine, lysoPC (18:1 (9Z)), creatine, taurochenodeoxycholic acid and taurocholic acid. Furthermore, we found that the relative content ratio between phosphatidylcholine and lysoPC (18:1 (9Z)) had a better distinguishing ability (AUC=0.867). The relative content ratio also had the feature to reduce systematic errors of sample processing and instrument detection, therefore having a greater value for clinical application.

Nine compounds were isolated from 95% ethanol extract of the roots of Tagates erecta by silica gel column chromatography and Sephadex LH-20 chromatography. Their structures were identified by spectroscopic data as 5-hydroxymethylfurfuryl methyl succinate (1), 5, 7, 3'-trihydroxyl-3, 6, 4'-trimethoxylflavone (2), syringic acid (3), 5, 7, 4'-trihydroxyl-3, 6-trimethoxylflavone (4), patuletin-4'-methoxyl-7-O-β-D-glucopyranoside (5), patulitrin (6), 5, 3'-dihydroxyl-3, 6, 4'-trimethoxylflavone-7-O-β-D-glucopyranoside (7), (2, 2'-biththiophen)-5-ol (8), and 3-hydroxyl-4-methoxyl benzoic acid (9). Among them, compound 1 is a new disubstituted succinate and compound 8 was isolated from a natural resource for the first time. Compounds 2, 4, 5 and 9 were isolated from this genus for the first time. By measuring the biological activity and virulence of different compounds against soybean cyst nematode, it has found that compounds 1-8 exhibited a toxic effect on soybean cyst nematode, and ED₅₀ values indicate that compounds 3 and 7 are the most potent, with ED₅₀ values of 0.008 μg·mL^-1.

6-Bromo-3-n-butylphthalide was obtained by nitration, reduction and diazotization from carboxybenzaldehyde. Twenty hybrids from substituted styrene and 6-bromo-3-n-butylphthalide were synthesized and the structure was confirmed by ¹H NMR, ¹³C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The mechanism of neuroprotection was investigated by Western blot analyses. The results indicated that most of these compounds had a potent neuroprotective activity (All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine), especially 10h and 10i showed significant effects, which may play a neuroprotective role by activating the PI3K/Akt signaling pathway.

Based on dehydrogenation of monocrotaline-induced Beagle dog model of pulmonary hypertension (PH), GC-TOF-MS metabolomics technique was used to identify potential biomarkers and biologically significant changes in the serum. Pattern recognition method was used for processing metabolomics data to compare PH Beagle dogs (n=11) versus healthy controls (n=8). The results show that 514 compounds were detected in the serum. The profiles of PH models and healthy controls can be distinguished clearly, indicating that there are significant differences in the metabolic profiles. Data analysis revealed 15 types of potential biomarkers, including amino acids glycine and 3-cyanoalanine, glucose, fructose, 1-monopalmitic acid glycerin, and malic acid. Diversified metabolites and their metabolic pathways have been analyzed. We found that different degrees of turbulence and disorganization occurred in glyoxylate and dicarboxylate metabolism, TCA cycle, starch and sucrose metabolism pathways in the Beagle dogs. A soluble guanylate cyclase activator, 4, 6-diamino-2-[1-(3-fluorothiophen-2-yl) methyl-1H-pyrazolo[3, 4-b]pyridin-3-yl] -5-pyrimidinyl-N-methyl methyl carbamate (sGC003), was administered (n=15) for comparison with the model and the control. We found that three groups were clearly clustered, indicating that there were differences in the three groups of metabolites. ANOVA statistical analysis results suggested that sGC003 exhibited pharmacodynamic effect, and at the same time, it also changed the endogenous metabolites to some extent. This study laid a foundation for the application of metabolomics in early diagnosis of pulmonary hypertension and provided experimental evidence for the application of sGC003 compound. In this study, the program of animal testing had been approved by Committee on the management of experimental animal in the Beijing Rixin Technology Co. Ltd.

This study aimed to address the protective role of Guilingji (GLJ) against hydrocortisone-induced Kidney-Yang deficiency syndrome in rats with metabolites in serum, and explore its regulative approaches. KidneyYang deficiency syndrome rat model was constructed by high-dose injection of hydrocortisone. Rats were randomly divided into 6 groups:control group, model group, positive (Jinkui Shenqi Wan) group and low, medium, or highdose group of GLJ for continuous administration over 30 days. The efficacy of GLJ was evaluated with traditional pharmacodynamic indicators (body weight, behavioral indicators, and biochemical parameters) after the model was replicated successfully. Animal experimentation was approved according to the Committee on the Ethics of Animal Experiments of Shanxi University. Serum metabolic profiles obtained by UHPLC-Q Exactive Orbitrap-MS were used to explore metabolic regulation mechanism of GLJ. The results showed that GLJ could significantly improve Kidney-Yang deficiency syndrome. Pathway analysis showed that leucine-isoleucine metabolism, ether ester metabolism, and bile acid metabolism were the main pathways, with the main mechanism of action involving energy balance, intestinal homeostasis and immune function.

The purpose of current study is to investigate the metabolic profile of a triptolide derivative (5R)-5-hydroxytriptolide in vitro. (5R)-5-Hydroxytriptolide was incubated with the hepatocytes of human, monkey, dog, rat or mouse, respectively. Compared with inactivated hepatocytes, four metabolites were identified in hepatocytes from all five species:oxidative ring-opening metabolite (M1), glutathione-conjugating metabolite (M2), and monooxidative combined with glutathione-conjugating metabolites (M3-1 and M3-2), respectively. In human or rat liver microsomes, seven metabolites of (5R)-5-hydroxytriptolide were found, dehydrogenated metabolite (M4) and monooxidative metabolites (M5-1-M5-6), respectively. Reference standards for the metabolites were obtained either through chemical semisynthesis or biotransformation through rat primary hepatocytes. The structures of five metabolites were confirmed, which were 12, 13-epoxy ring-opening metabolite M1, 12-glutathione-conjugating metabolite M2, (16S)-, (2R)- and (19R)-monohydroxylated metabolites M5-1, M5-4, and M5-5, respectively. In vitro activity assay revealed that only (2R)-hydroxylated metabolite exhibited weak immunosuppressive activity with less than one-tenth the activity of its parent drug, and a significant decrease in toxicity was observed. It is suggested that (5R)-5-hydroxytriptolide might undergo metabolic inactivation and detoxification in vivo.

The aim of this study is to solidify the volatile oil (VO) of Bupleuri radix and forsythiae fructus by using mesoporous silica Sylysia 350FCP (Sylysia 350FCP) as carrier, and to investigate the changes of micromeritic properties before and after drug loading. The volatile oil drug-loading powder (VO-DLP) was prepared by blending process. The micromeritic properties were evaluated by angle of repose, particle size, bulk density, true density and porosity. The compressibility and compactibility of the powder were evaluated by plastic strain energy, ejection force, friction energy and tensile strength. The powder was characterized by scanning electron microscopy, powder X-ray diffraction and synchronous thermal analysis. In addition, the thermal stability, mechanical stability and other key properties of VO-DLP were investigated. We found that mesoporous silica as a carrier of solidifying volatile oil has the advantages for large drug load, high thermal stability, and high mechanical stability. In addition, the excellent properties of mesoporous silica as solid lubricant and glidant are not affected after loading VO, and has no effect on the compression process and compactibility of materials. What's more, it can meet the demand of continuous production.

This study aims to develop multifunctional drug delivery system based on hollow mesoporous copper sulfide (HMCuS) nanoparticles. This type of nanoparticles is expected to achieve the synergistic treatment of tumor by targeted phototherapy and chemotherapy. The carrier was synthesized by a substitution method, and the anti-cancer drug doxorubicin (DOX) was loaded and then modified by hyaluronic acid (HA) to prepare the anticancer drug system DOX/HMCuS-HA. The results suggested that DOX/HMCuS-HA presented uniform spherical structure, with the drug loading efficiency of 33.6%, the particle size and zeta potential being 113.8±6.9 nm and 18.4±2.8 mV, respectively. When 100 μg·mL^-1 HMCuS was irradiated under 808 nm laser (2 W·cm^-2) for 8 min, the temperature can heat up 51℃, demonstrating high photothermal conversion efficacy. Electron spin resonance (ESR) tests and methylene blue degradation experiments showed that HMCuS nanoparticles could simultaneously produce hydroxyl radical (·OH) mediated photodynamic therapy. In addition, HA was responsible for minimizing premature drug release and increasing tumor targeting efficiency by acting as a smart gatekeeper with tumor specific targeting moiety. In vitro drug release experiments showed that the coated HA could be degraded by intracellular lysosomal enzyme hyaluronidase, which facilitated DOX release. The acidic microenvironment of tumor cell and external near infrared (NIR) stimulus could trigger further release of DOX from the nanoparticles. These results point to a new strategy for timely and effective anti-tumor treatment.

The surface hydrophobicity of nanoparticles plays an important role in drug delivery process. The aim of this study was to verify the feasibility of using self-assembly method to prepare drug-loaded nanoparticles with tunable surface hydrophobicity. Here, Soluplus was selected as the polymeric carrier to prepare panobinostat (PNB) loaded micelles. Three different monoglycerides, glycerly monooleate (GMO), glycerly linoleate (GML) and glycerly linolenate (GMLO), were used to modify the surface of PNB-Soluplus micelles to prepare polymerlipid hybrid nanoparticles (PLHNs). The effect of monoglyceride type and amount on the physico-chemical properties of PNB-loaded PLHNs was investigated, and the surface hydrophobicity of PLHNs was characterized by Rose Bengal (RB) binding method and mucin particle method. The results suggested that compared with the PNB-Soluplus micelles (particle size 77.97±0.78 nm, zeta potential 0.44±0.29 mV, entrapment efficiency 99.45%±1.47%, the RB binding constant (K) value 0.008±0.002, the increased particle size after mixing with mucin particles 7.90±1.41 nm), surface hydrophobicity of the PLHNs increased significantly when modified by GMO, GML, GMLO, with K values of 0.055±0.010, 0.050±0.011 and 0.058±0.008, respectively. The increased particle sizes after mixing with mucin particles were 17.37±4.48 nm, 22.60±2.10 nm and 25.13±3.89 nm, respectively. Among them, the physico-chemical properties of the GMLO modified PNB-loaded PLHNs (particle size 81.60±4.52 nm, zeta potential 0.77±0.03 mV, entrapment efficiency 99.59%±0.20%) kept constant, thus GMLO was selected to further investigate the effect of GMLO mass ratio (1%-3%) to Soluplus on the properties of the nanoparticles. While no statistical significant difference in particle size, zeta potential, entrapment efficiency or in vitro release behavior was found when GMLO ratio increased, the surface lipophilicity of the PLHNs, as characterized by K values and the increased particle sizes after mixing with mucin particles, increased almost linearly with the increase of GMLO amount. In conclusion, we demonstrated that drug-loaded PLHNs based on Soluplus and GMLO can be prepared by self-assembly method, and the surface hydrophobicity was tunable by modifying the mass ratio of GMLO to Soluplus. This approach could be used for related basic science research aiming to elucidate the effect of surface hydrophobicity on in vivo behavior of drug-loaded system.

UDP-rhamnose is a rhamnose donor in a reaction catalyzed by UDP-rhamnose synthase (RHM), and plays an important role in the biosynthesis of rhamnoside compounds. The current literature suggests that there are only a few genes can encode the corresponding enzymes to participate in UDP-rhamnose biosynthesis in plants. In this study, two RHM genes (FmRHM1 & 2) were first cloned by using the transcriptomic data of Fallopia multiflora (Thunb) Harald and the multidimensional analysis, including bioinformatics, functional identification in vitro and tissue-specific expression analysis. The results showed that the open reading frame (ORF) of FmRHM1 & 2 genes both were 2 013 bp, encode proteins consisting of 670 amino acids with a calculated molecular mass of 75.6 kDa, and the theoretical isoelectric points of 6.20 and 7.19, respectively. Bioinformatic analysis also indicated that FmRHM1 & 2 contained 2 special sequences of GxxGxxG/A and YxxxK. The phylogenetic analysis showed that the FmRHM gene has a high homology with RHM of other species. The results of enzyme activity in vitro revealed that both recombinant FmRHM1 and FmRHM2 have catalytic activities for converting UDP-glucose into UDP-rhamnose. Measurements of tissue-specific expressions showed that the expression levels of FmRHM1 and FmRHM2 were lower in roots. On the contrary, the 2 genes showed significantly high expression in the stems and leaves. In conclusion, we have cloned and characterized the RHM gene function for the first time in F. multiflora. Here we have provided the preliminary data suggesting the need for further research on UDP-rhamnose biosynthesis by microorganisms.