To Explore the Clinical Application Value of the Ilizarov Bone Handling Technique in the Treatment of Tibial Bone Defects Caused by Osteomyelitis Segmental Resection.

Objective: To study the application value of Ilizarov bone handling technology in the treatment of tibial bone defect caused by osteomyelitis segmental resection. Methods: 78 patients with tibial bone defects after osteomyelitis segmental resection admitted to our hospital from January 2018 to August 2019 were retrospectively analyzed and assigned to the Ilizarov bone handling group (38 cases) and the fibular segmental transplantation group (40 cases). The perioperative indexes between the groups were compared (external fixation time, complete weight-bearing time, and intraoperative bleeding volume). The ankle function and knee function of patients were assessed before and 6 months after treatment and the occurrence of postoperative complications were counted. Results: The external fixation time and full weight-bearing time in the Ilizarov bone handling group were significantly shorter than those in the fibular segment transplantation group, and the intraoperative bleeding was less, with statistically significant differences (P < .05). Compared to the pre-treatment period, Baird's scores and HHS scores of the patients in both groups increased significantly after 6 months of treatment, and both scores in the Ilizarov bone handling group were significantly higher than those in the fibular segment transplantation group, and the differences were statistically significant (P < .05). The postoperative complication statistics showed that the complication rate of the Ilizarov bone handling group was significantly lower than that of the fibular segment transplantation group (P < .05). Conclusion: The Ilizarov bone transfer technique is less invasive than the fibular bone grafting technique used in the treatment of patients with osteomyelitis segmental resection-induced tibial bone defects, with the former having the advantages of less traumatization, faster recovery of the patients, better recovery of knee and ankle functions, and fewer complications, which is of high value for clinical application.

Regulation of the colon-targeted release rate of lactoferrin by constructing hydrophobic ethyl cellulose/pectin composite nanofibrous carrier and its effect on anti-colon cancer activity.

In order to modify colonic release behavior of lactoferrin (Lf), a hydrophobic composite nanofibrous carrier (CNC) was constructed by emulsion coaxial electrospinning. Ethylcellulose/pectin based water-in-oil emulsion and Lf-contained polyvinyl alcohol solution were used as shell and core fluids, respectively. An electrospinning diagram was first constructed to screen out suitable viscosity (51-82 cP) and conductivity (960-1300 µS/cm) of the dispersed phase of pectin solution for successful electrospinning of shell emulsion. Varying mass fraction of pectin solution (5 %-20 %) of shell emulsion during emulsion coaxial electrospinning obtained CNCs with different micro-structures, labeled as 5&95 CNC, 10&90 CNC, 15&85 CNC, 20&80 CNC. These CNCs all achieved colonic delivery of Lf (>95 %), and the time for complete release of Lf in simulated colon fermentation process were 10, 7, 5 and 3 h, respectively. That is, the greater the pectin content in CNC, the faster the release rate of stabilized Lf in colon. Lf release in simulated colon fermentation fluid involved complex mechanisms, in which diffusion release of Lf was dominant. Increasing colonic release rate of Lf enhanced its regulation effect on the expression levels of cell cycle arrest and apoptosis-related protein and promote its effective inhibition on the proliferation of HCT116 cell.

Enzymatic activity of 38 CYP2C9 genotypes on ibuprofen.

BACKGROUND AND OBJECTIVE: Ibuprofen, a common non-steroidal anti-inflammatory drug, is used clinically for pain relief and antipyretic treatment worldwide. However, regular or long-term use of ibuprofen may lead to a series of adverse reactions, including gastrointestinal bleeding, hypertension and kidney injury. Previous studies have shown that CYP2C9 gene polymorphism plays an important role in the elimination of various drugs, which leads to the variation in drug efficacy. This study aimed to evaluate the effect of 38 CYP2C9 genotypes on ibuprofen metabolism. METHODS: Thirty-eight recombinant human CYP2C9 microsomal enzymes were obtained using a frugiperda 21 insect expression system according to a previously described method. Assessment of the catalytic function of these variants was completed via a mature incubation system: 5 pmol CYP2C9*1 and 38 CYP2C9 variants recombinant human microsomes, 5 µL cytochrome B5, ibuprofen (5-1000 µM), and Tris-HCl buffer (pH 7.4). The ibuprofen metabolite contents were determined using HPLC analysis. HPLC analysis included a UV detector, Plus-C18 column, and mobile phase [50% acetonitrile and 50% water (containing 0.05% trifluoroacetic acid)]. The kinetic parameters of the CYP2C9 genotypes were obtained by Michaelis-Menten curve fitting. RESULTS: The intrinsic clearance (CLint) of eight variants was not significantly different from CYP2C9*1; four CYP2C9 variants (CYP2C9*38, *44, *53 and *59) showed significantly higher CLint (increase by 35%-230%) than that of the wild-type; the remaining twenty-six variants exhibited significantly reduced CLint (reduced by 30%-99%) compared to that of the wild-type. CONCLUSION: This is the first systematic evaluation of the catalytic characteristics of 38 CYP2C9 genotypes involved ibuprofen metabolism. Our results provide a corresponding supplement to studies on CYP2C9 gene polymorphisms and kinetic characteristics of different variants. We need to focus on poor metabolizers (PMs) with severely abnormal metabolic functions, because they are more susceptible to drug exposure.

Targeting CD73 increases therapeutic response to immunogenic chemotherapy by promoting dendritic cell maturation.

The CD39-CD73-adenosinergic pathway converts adenosine triphosphate (ATP) to adenosine for inhibiting anti-tumor immune responses. Therefore, targeting CD73 to reinvigorate anti-tumor immunity is considered the novel cancer immunotherapy to eradicate tumor cells. To fully understand the critical role of CD39/CD73 in colon adenocarcinoma (COAD), this study aims to comprehensive investigate the prognostic significance of CD39 and CD73 in stage I-IV COAD. Our data demonstrated that CD73 staining strongly marked malignant epithelial cells and CD39 was highly expressed in stromal cells. Attractively, tumor CD73 expression was significantly associated with tumor stage and the risk of distant metastasis, which suggested CD73 was as an independent factor for colon adenocarcinoma patients in univariate COX analysis [HR = 1.465, 95%CI = 1.084-1.978, p = 0.013]; however, high stromal CD39 in COAD patients was more likely to have favorable survival outcome [HR = 1.458, p = 1.103-1.927, p = 0.008]. Notably, high CD73 expression in COAD patients showed poor response to adjuvant chemotherapy and high risk of distant metastasis. High CD73 expression was inversely associated with less infiltration of CD45+ and CD8+ immune cells. However, administration with anti-CD73 antibodies significantly increased the response to oxaliplatin (OXP). Blockade of CD73 signaling synergistically enhanced OXP-induced ATP release, which is a marker of immunogenic cell death (ICD), promotes dendritic cell maturation and immune cell infiltration. Moreover, the risk of colorectal cancer lung metastasis was also decreased. Taken together, the present study revealed tumor CD73 expression inhibited the recruitment of immune cells and correlated with a poor prognosis in COAD patients, especially patients received adjuvant chemotherapy. Targeting CD73 to markedly increased the therapeutic response to chemotherapy and inhibited lung metastasis. Therefore, tumor CD73 may be an independent prognostic factor as well as the potential of therapeutic target for immunotherapy to benefit colon adenocarcinoma patients.

Chemical Characterization and Atherosclerosis Alleviation Effects of Gypenosides from Gynostemma pentaphyllum through Ameliorating Endothelial Dysfunction via the PCSK9/LOX-1 Pathway.

Dietary saponins have the potential to ameliorate atherosclerosis (AS). Gypenosides of Gynostemma pentaphyllum (GPs) have been used as functional foods to exhibit antiatherosclerotic activity. The present study aimed to explore the protective effect, underlying mechanism and active substances of GPs on AS in vivo and in vitro. Results demonstrated GPs administration reduced the serum concentrations of TC and LDL-C, upregulated the plasma HDL-C content, inhibited the secretion of ICAM-1, VCAM-1, and MCP-1, and alleviated vascular lesions in VitD3 plus high cholesterol diet-induced AS rats as well as reduced adhesion factors levels in ox-LDL-stimulated HUVECs, which was potentially associated with suppressing PCSK9/LOX-1 pathway. Further activity-guided phytochemical investigation of GPs led to the identification of five new dammarane-type glycosides (1-5) and ten known analogs (6-15). Bioassay evaluation showed compounds 1, 6, 7, 12, 13, and 14 observably reduced the expressions of PCSK9 and LOX-1, as well as the secretion of adhesion factors in injured HUVECs. Molecular docking experiments suggested that the active saponins of GPs might bind to the allosteric pocket of PCSK9 located at the catalytic and C-terminal domains, and 2α-OH-protopanaxadiol-type gypenosides might exert a higher affinity for an allosteric binding site on PCSK9 by hydrogen-bond interaction with ARG-458. These findings provide new insights into the potential nutraceutical application of GPs and their bioactive compounds in the prevention and discovery of novel therapeutic strategies for AS.

Exploring Meaning of Life in Women With Breast Cancer in Taiwan: A Phenomenological Study.

BACKGROUND: Globally, breast cancer is the most common cancer type in terms of incidence for women. Women with breast cancer endure higher levels of psychological distress than other types of cancer because many lose their identity as a woman, which is an additional characteristic of their psychological distress. Research using phenomenology to explore "the meaning of life" is rare among women with breast cancer. PURPOSE: The purpose of this study was to explore the perspectives of women with breast cancer on "the meaning of life." METHODS: A phenomenological approach was used. Twenty-six women living with breast cancer drawn from a cancer treatment hospital in Taiwan participated in this study. A semistructured interview was utilized to collect the data, and Colaizzi's seven steps were used to analyze the data. RESULTS: Four themes emerged: (a) value of overcoming suffering, (b) value of reciprocal love, (c) value of self-transcendence, and (d) value of spiritual comfort. This means that the participants defined "the meaning of life" through the lens of suffering from cancer, reciprocal love from their families and friends, uncovering and discovering creative pathways that transformed their pain while searching for the value of their existence, and seeking spiritual guidance from religion. CONCLUSIONS: The participants identified the most pivotal aspect of healing as transforming their pain and accepting value for their suffering. They acknowledged they could not change the fact that they had cancer, but they could learn to accept it as part of their lived experience. Healthcare professionals may use these four themes at a clinically appropriate time on women's journeys toward healing to inspire women with breast cancer to process their own unique "meaning of life."

Expert Consensus on Rheumatic Immune Diseases Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

In the clinical practice of rheumatic immune diseases in traditional Chinese medicine （TCM），it`s still unclear about the dominant diseases and breakthrough points. It`s urgent missions to formulate TCM diagnosis and treatment guidelines widely recognized and integrated by traditional Chinese medicine and Western medicine. In order to clarify the dominant diseases and breakthrough points in rheumatism，China association of Chinese medicine initiated a research group covering experts in the field of rheumatism of traditional Chinese medicine and Western medicine. Based on questionnaire survey and on-site discussion，experts had reached the following consensus. Evidence-based medicine research using modern medical methods and scientific methods should be carried out to provide objective clinical evidences. "Four mutuality" were put forward as the basis for the work of integrated traditional Chinese and Western medicine，that is the mutual communication using the exchangeable context，the mutual explanation using common theories，the mutual certification using common standards，and the mutual integration using common means. Key works should focus on solving refractory rheumatism in the future. In terms of dominant diseases and breakthrough points，this paper introduces 21 breakthrough points in 6 dominant diseases，including rheumatoid arthritis，ankylosing spondylitis，Sjogren's syndrome，hyperuricemia and gout，systemic lupus erythematosus and fibromyalgia syndrome. Advice on this discussion can provide valuable references for developing the treatment scheme of rheumatism with TCM and integrated Chinese and Western medicine and clinical practice and scientific research.

Kaempferia galanga L.: Progresses in Phytochemistry, Pharmacology, Toxicology and Ethnomedicinal Uses.

K. galanga is an aromatic medicinal herb. It is locally to India and distributed in China, Myanmar, Indonesia, Malaysia, and Thailand. K. galanga is a Traditional Chinese Herb Medicine (TCHM), which has been applied to treat cold, dry cough, toothaches, rheumatism, hypertension and so on. In addition, it has been used widely as spices since its highly aromas. The aim of this review is to compile and update the current progresses of ethnomedicinal uses, phytochemistry, pharmacology and toxicology of K. galanga. All the data on K. galanga were based on different classical literary works, multiple electronic databases including SciFinder, Web of Science, PubMed, etc. The results showed that ninety-seven compounds have been identified from rhizome of K. galanga, including terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids and esters. Modern pharmacology studies revealed that extracts or secondary metabolites of the herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, and anti-angiogenesis effects, which were closely related to its abundant ethnomedicinal uses. In conclusion, although previous research works have provided various information of K. galanga, more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb.

Tetramethylpyrazine induces the release of BDNF from BM-MSCs through activation of the PI3K/AKT/CREB pathway.

Compelling evidences suggest that transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) can be therapeutically effective for central nervous system (CNS) injuries and neurodegenerative diseases. The therapeutic effect of BM-MSCs mainly attributes to their differentiation into neuron-like cells which replace injured and degenerative neurons. Importantly, the neurotrophic factors released from BM-MSCs can also rescue injured and degenerative neurons, which plays a biologically pivotal role in enhancing neuroregeneration and neurological functional recovery. Tetramethylpyrazine (TMP), the main bioactive ingredient extracted from the traditional Chinese medicinal herb Chuanxiong, has been reported to promote the neuronal differentiation of BM-MSCs. This study aimed to investigate whether TMP regulates the release of neurotrophic factors from BM-MSCs. We examined the effect of TMP on brain-derived neurotrophic factor (BDNF) released from BM-MSCs and elucidated the underlying molecular mechanism. Our results demonstrated that TMP at concentrations of lower than 200 µM increased the release of BDNF in a dose-dependent manner. Furthermore, the effect of TMP on increasing the release of BDNF from BM-MSCs was blocked by inhibiting the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/cAMP-response element binding protein (CREB) pathway. Therefore, we concluded that TMP could induce the release of BDNF from BM-MSCs through activation of the PI3K/AKT/CREB pathway, leading to the formation of neuroprotective and proneurogenic microenvironment. These findings suggest that TMP possesses novel therapeutic potential to promote neuroprotection and neurogenesis through improving the neurotrophic ability of BM-MSCs, which provides a promising nutritional prevention and treatment strategy for CNS injuries and neurodegenerative diseases via the transplantation of TMP-treated BM-MSCs.

Gypenoside LVI improves hepatic LDL uptake by decreasing PCSK9 and upregulating LDLR expression.

BACKGROUNDS: Atherosclerotic Cardiovascular Disease (ASCVD) is defined as ischemic or endothelial dysfunction-various inflammatory diseases, which is mainly caused by excessive low-density lipoprotein cholesterol (LDL-C) in circulating blood. Gynostemma pentaphyllum is a traditional Chinese medicine, and total Gypenosides are used for the treatment of hyperlipidemia and to reduce circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) level. However, which gypenoside involved in the modulation of PCSK9 expression is still unknown. PURPOSE: This study aimed to discover effective PCSK9 inhibitors from Gypenosides in accordance with the 2019 ESC/EAS guidelines. METHODS: HPLC was employed to determine major six components of Gypenosides. The inhibitory activity on secreted PCSK9 in HepG2 of six major compounds from Gypenosides were screened by ELISA. The level of low-density lipoprotein (LDL) receptor (LDLR) was determined by Flow cytometry and Immunofluorescence. The expression levels of PCSK9, LDLR and Sterol-regulatory element binding proteins-2 (SREBP-2) were analyzed by qPCR and Western blot. DiI-LDL was added to evaluated LDL uptake into HepG2. RESULTS: The results suggested that the mRNA and protein levels of PCSK9 were down-regulated by Gypenoside LVI and the LDLR degradation in lysosomes system was inhibited, thereby leading to an increasing in LDL uptake into HepG2 cells. Furthermore, Gypenoside LVI decreased PCSK9 expression induced by stains. Altogether, Gypenoside LVI enhances LDL uptake into HepG2 cells by increased LDLR level on cell-surface and suppressed PCSK9 expression. CONCLUSION: This indicates that Gypenoside LVI can be used as a useful supplement for statins in the treatment of hypercholesterolemia. This is firstly reported that monomeric compound of G. pentaphyllum planted in Hunan province has the effect of increasing LDL-C uptake in hepatocytes via inhibiting PCSK9 expression.

Ethanol extract of Gynura bicolour reduces atherosclerosis risk by enhancing antioxidant capacity and reducing adhesion molecule levels.

CONTEXT: Gynura bicolour (Roxb. and Willd.) DC (Asteraceae) leaf is a common vegetable. Ethanol extracts of fresh G. bicolour leaves (GBEE) have several physiological effects, but studies on atherosclerosis are limited. OBJECTIVE: We investigated the oxidant scavenging ability and vascular adhesion molecule expression of these extracts. MATERIALS AND METHODS: The antioxidant effects of 0.05-0.4 mg/mL GBEE were analyzed in vitro. Intracellular antioxidant capacity and adhesion molecule levels were detected in EA.hy926 cells pre-treated with 10-100 µg/mL GBEE for 8 h, then TNF-α for 3 h. The antioxidant capacity of red blood cells and the adhesion molecule levels in the thoracic aorta were detected in high-fat diet (HFD)-fed Sprague-Dawley rats treated with GBEE for 12 weeks. RESULTS: The in vitro EC50 values of GBEE based on its DPPH radical-scavenging ability, reducing power, and ferrous ion-chelating ability were 0.20, 3.21 and 0.49 mg/mL, respectively. In TNF-α-treated EA.hy926 cells, the thiobarbituric acid-reactive substance levels were decreased after 10, 50, or 100 µg/mL GBEE treatments (IC50: 19.1 mg/mL). When HFD-fed rats were co-treated with GBEE, the GBEE-H group exhibited 25% higher glutathione levels than the HFD group (p < 0.05). E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion protein-1 levels were decreased in TNF-α-treated EA.hy926 cells after GBEE treatment (by approximately 11-73%; p < 0.05), and the above three adhesion molecules levels were decreased in HFD-fed rats with combined GBEE treatment (by approximately 30-77%; p < 0.05). CONCLUSIONS: GBEE can protect the vascular endothelium by reducing adhesion molecule expression and regulating antioxidants. It may have the potential to prevent atherosclerosis.

Four new phenanthrene derivatives from Bulbophyllum retusiusculum.

Three new dihydrophenanthrenes, retusiusine D (1), retusiusine E (2), retusiusine F (3), and a new phenanthrene retusiusine G (4), together with two known dihydrophenanthrenes 4,7-dihydroxy-2,3-methylenedioxy-9,10-dihydrophenanthrene (5) and epemeranthol-A (6) were isolated from the tubers of Bulbophyllum retusiusculum. Their structures were established on the basis of extensive spectroscopic analyses. Compounds 1 and 2 exhibited potent cytotoxic activities against SMMC-7721 and weak cytotoxic activities against HL-60. Compound 4 showed moderate cytotoxic activity against SMMC-7721 and MCF-7.

UPLC-ESI-Q-TOF/MS Based Metabolic Profiling of Protosappanin B in Rat Plasma, Bile, Feces, Urine and Intestinal Bacteria Samples.

BACKGROUND: Caesalpinia sappan L. is a traditional medicinal plant that is used to promote blood circulation and treat stroke in China. Protosappanin B (PTB) is a unique homoisoflavone compound isolated from Sappan Lignum (the heartwood of Caesalpinia sappan L). In a previous study, the metabolic fate of PTB remained unknown. OBJECTIVE: To explore whether PTB is extensively metabolized, the metabolites of PTB in bile, plasma, urine, feces, and intestinal bacteria samples in rats were investigated. METHODS: The biosamples were investigated by ultraperformance liquid chromatography combined with time-offlight mass spectrometry (UPLC-TOF-MS/MS) with MetabolitePilot software. RESULTS: 28 metabolites were identified in the biosamples: 18 metabolites in rat bile, 8 in plasma, 20 in feces, 7 in urine and 2 in intestinal bacteria samples. Both phase I and phase II metabolites were observed. Metabolite conversion occurred via 9 proposed pathways: sulfate conjugation, glucuronide conjugation, bis-glucuronide conjugation, glucose conjugation, dehydration, oxidation, hydrolysis, methylation and hydroxymethylene loss. The metabolic pathways differed among biosamples and exhibited different distributions. Among these pathways, the most important was sulfate and glucuronide conjugation. CONCLUSION: The results showed that the small intestinal and biliary routes play an important role in the clearance and excretion of PTB. The main sites of metabolism in the PTB chemical structure were the phenolic hydroxyl and the side-chains on the eight-element ring.

Comprehensive evaluation of NAODESHENG by combining UPLC quantitative fingerprint and antioxidant activity.

The screening of marker compound is of great significance to the quality control of traditional Chinese medicine (TCM). One approach which combines fingerprint and biological evaluation has developed rapidly. Multi-wavelength fusion fingerprints and antioxidant activity screening are integrated in this study to evaluate the quality of NAODESHENG. Characteristic multiwavelength fusion fingerprints of 14 batches of samples were generated at five different wavelengths and evaluated by quantitative fingerprinting with ultra-performance liquid chromatography (UPLC). In the quantitative fingerprinting method, 21 components in NAODESHENG were qualitatively and quantitatively analyzed by external standard method. The antioxidant activities of these 21 components was determined by pre-column antioxidant activity test. Multivariate statistical methods such as hierarchical clustering analysis and principal component analysis(PCA) was used to reduce the dimensions and variables from a large number of original data to screening marker compound with bioactivity. Based on the above results, it is suggested that 3'-Methoxy Puerarin and 11 other components should be used as the quality marker of NAODESHENG. This study demonstrates the feasibility of multi-wavelength fusion fingerprinting combined with antioxidant activity analysis, which associates quality control with bioactivity, providing a reliable and efficient method for quantitative assessment of TCM quality consistency.

HYR-2 plays an anti-lung cancer role by regulating PD-L1 and Akkermansia muciniphila.

Traditional Chinese medicine (TCM) plays a vital part in cancer treatment due to its unique superiority. Huoxue Yiqi Recipe-2 (HYR-2) was supposed to have therapeutic effect on lung cancer, which came from Ze Qi Decoction in one of the four great classics of TCM called "Synopsis of Prescriptions of the Golden Chamber". Network pharmacology demonstrated that the targets of active components from HYR-2 were significantly enriched in the signaling pathways, which were closely associated with non-small cell lung cancer (NSCLC) and programmed death ligand 1 (PD-L1). Then, data about NSCLC was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET was analyzed by bioinformatics, and 214 biomarkers for NSCLC were obtained, containing 14 targets of active components from HYR-2 (which were significantly enriched in the PD-L1 related signaling pathway). In vivo and in vitro experiments showed that HYR and HYR-2 could inhibit the growth of lung cancer and down-regulate the expression of PD-L1, which might be related to the blocking effect of HYR-2 on the PI3K/Akt signaling pathway. Furthermore, HYR-2 promoted the transformation of M2 macrophages into M1 macrophages as well. It is deserved to be mentioned that the level of Akkermansia muciniphila was also significantly elevated by HYR-2, which was believed to enhance the therapeutic effect of PD-L1 antibodies. To sum up, HYR-2 might play an anti-lung cancer effect by down-regulating PD-L1 together with up-regulating Akkermansia muciniphila.

Development of a polysaccharide based multi-unit nanofiber mat for colon-targeted sustained release of salmon calcitonin.

Advances in pharmaceutical technology have promoted the development of colon-targeted delivery system for oral administration of bioactive peptides or proteins to enhance their bioavailability. In this study, a multi-unit nanofiber mat was fabricated by coaxial electrospinning and its feasibility as the colon-targeted delivery system for a bioactive peptide, salmon calcitonin (sCT), was investigated. Sodium alginate and sCT-loaded liposome coated with pectin served as the shell layer and core layer, respectively. An in vitro study demonstrated that the encapsulated sCT was released in a sustained and colon-targeted way. Analysis using different mathematical models showed that release followed a complex mechanism. In addition, greater amounts of sCT were released from the core-shell nanofiber mat into simulated colon fluid (SCF) than was released from a uniaxial nanofiber mat (65.2% vs. 47.8%). The use of a core-shell nanofiber mat further alleviated the burst release of sCT into simulated gastric and intestinal fluid (SGF and SIF), demonstrating the superiority of a multi-unit vehicle for colon-targeted delivery of sCT. Furthermore, 88% of the bioactivity of encapsulated sCT was retained. This multi-unit vehicle offers a better-designed vehicle for the colon-targeted sustained release of bioactive peptides or proteins and, thus, should improve oral bioavailability.

The factors affecting a native obligate parasite, Cuscuta australis, in selecting an exotic weed, Humulus scandens, as its host.

In weed management, using native parasites to control exotic weeds is considered a better alternative than classical biological control. But the risk must be assessed because of the potential damage caused by these agents. We conducted this project to investigate the mechanism driving the choice of a native obligate parasite, Cuscuta australis, between the exotic, Humulus scandens, and native plants as its host through field and pot experiments. The results showed that C. australis preferred the exotic weed over native (naturalized) hosts and caused a notable reduction in the biomass of H. scandens in the field. In contrast, the results of the pot experimentindicated that C. australis preferred a mix of native (naturalized) hosts over the exotic weed. Both texperiments indicated that the parasitic preference of C. australis was induced more by light irradiance than plant water, carbon (C), nitrogen (N) and phosphorus (P) contents, indicating that the native parasite can only be used to control H. scandens when the exotic weed forms mono-cultures or dominates the community. Accordingly, induction and release of C. australis to control H. scandens should be conducted with great caution.

Melosuavine I, an apoptosis-inducing bisindole alkaloid from Melodinus suaveolens.

A new bisindole alkaloid, melosuavine I (1) possessing an aspidosperma-aspidosperma dimeric skeleton, was isolated from the leaves of Melodinus suaveolens. The structure with absolute configuration of 1 was elucidated by a combination of MS, NMR and computational methods. MTT assays indicated that 1 exhibited significant cytotoxicity on human breast cancer BT549 cells with an IC50 value of 0.89 µM. Further study showed that 1 inhibited BT549 cell proliferation by inducing apoptosis through activation of caspase 3 and p53, and down-regulation of Bcl-2.

Direct Observation of Oxidation Reaction via Closed Bipolar Electrode-Anodic Electrochemiluminescence Protocol: Structural Property and Sensing Applications.

In this work, we developed an innovative closed bipolar electrode (BPE)-electrochemiluminescence (ECL) sensing strategy with generality for target detection. Based on charge balance and 100% current efficiency between the closed BPE poles and the driving electrodes, one of the driving electrodes in one cell of the closed BPE system was employed as ECL sensing surface to reflect the target on the BPE pole in the opposite cell. Compared with traditional BPE-ECL sensing method, which in general adopted the anodic ECL reagents such as Ru(bpy)32+ and its coreactant on one pole (anode) to reflect the target (occurring reduction reaction) on the other pole (cathode), the difference was that the targets occurring oxidation reaction could be detected by the anodic ECL reagents based on this strategy. To verify the feasibility of this strategy, the detection principle was stated first, and Fe(CN)64- as model target at anodic BPE pole were detected by anodic ECL reagents (Ru(bpy)32+ and TprA) on the driving electrode first. The ECL signals showed good performance for target detection. By changing the size and the material of the BPE pole where the targets were located, the detection of l-ascorbic acid (AA), uric acid (UA), and dopamine (DA) as other model targets with higher detection limit were accomplished. Visual and high-throughput detection of AA, UA, and DA were also successfully realized by an array of the closed BPE system. This closed BPE (array) system is an effective supplement of traditional BPE-ECL sensing and could greatly expand the scope of the detection target.

New phenylpropanoids from Bulbophyllum retusiusculum.

Two new phenylpropanoids, retusiusines A (1) and B (2), and a pair of new phenylpropyl enantiomers, (±)-retusiusine C (3a and 3b), together with eight known compounds, dihydroconiferyl dihydro-p-coumarate (4), methyl 3-(4-hydroxyphenyl) propionate (5), 3-(4-hydroxyphenyl)-propanoic acid (6), dihydroferulic acid (7), methyl 3-(4-methoxyphenyl) propionate (8), 3-(3,4-dimethoxyphenyl)-2-propenal (9), trans-p-coumaric acid (10) and dihydroconiferyl alcohol (11), were isolated from the tubers of Bulbophyllum retusiusculum. The absolute configurations of the new compounds were determined by calculating their electronic circular dichroism (ECD), spectra and specific optical rotations and comparing the calculated values with the experimental data. Compound 2 exhibited potent antifungal activity against Candida albicans (16 µg/mL). Compound 3 showed moderate antibacterial activity against Bacillus subtilis (64 µg/mL).