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PurposeDuring the current global epidemic, e-learning and mobile learning have been rapidly developed in the field of entrepreneurship education. The effect of these learning methods remains to be confirmed. The purpose of this paper is to explore the effect of mobile business simulation games in entrepreneurship education.Design/methodology/approachFrom May 2020 to July 2020, the authors adopted a quasi-experimental design to explore the effect of mobile business simulation games in entrepreneurship education. The authors set up an experimental group to participate in mobile business simulation games, with a total of 105 students, and set up a control group of 100 students. At the beginning and end of the experiment, data on entrepreneurial attitude, self-efficacy, entrepreneurial intention and other related variables were collected. Paired sample T-test and regression analysis were used to analyze the results.FindingsThe authors found that mobile business simulation games can improve entrepreneurial attitudes and self-efficacy, but cannot change entrepreneurial intentions. The paired sample T-test in the experimental group showed that the entrepreneurial attitude and entrepreneurial self-efficacy of the participants were significantly improved, but the entrepreneurial intention did not change significantly. The above three variables did not change significantly in the control group. The research results also show that flow experience is very important in mobile business simulation games, which can improve entrepreneurial attitude and entrepreneurial self-efficacy.Originality/valueThe authors’ findings confirm the positive effects of mobile business simulation games in entrepreneurship education, which can improve entrepreneurial attitudes and entrepreneurial self-efficacy. But the disadvantage of mobile business simulation games is that they cannot increase entrepreneurial intention. In addition, the flow experience needs to be valued in mobile business simulation games. The research in this paper has implications for how mobile learning can be used in entrepreneurship education during the COVID-19 pandemic. In addition, research is of great value on how mobile business simulation games can be improved.

Business simulation games (BSGs) have been widely used in entrepreneurship education with positive effects. However, there are still some deficiencies in the BSGs, such as limited guidance, low uncertainty and limited simulation environment, which make it impossible to exert the maximum effect. Artificial intelligence (AI) can solve the above shortcomings. The combination of AI and BSGs is the possible development direction of BSGs. But how to effectively combine BSGs with AI is still an open question. Using a quasi-experimental design, this study uses fuzzy-set qualitative comparative analysis to analyze how participants’ entrepreneurial attitude changes in BSGs. The results show that BSGs can effectively improve entrepreneurial attitude, and there are four types of promotion configurations. These four configurations consist of five antecedent conditions. According to the above conclusions, AI can improve entrepreneurial attitude in BSGs in various ways, such as simulating competitors, providing targeted feedback for failures, and improving game experience. The contribution of this paper is to highlight the possibility of combining AI with BSGs, and to provide suggestions on how AI can intervene in BSGs.

A new phenolic glycoside, chinenside A (1), and a new megastigmane glycoside, chinenionside A (2), together with twelve known compounds (3-14), were isolated from the roots of Alangium chinense. Their structures were deduced on the basis of extensive spectroscopic analyses and comparison with data reported in the literature. The anti-inflammatory activity in vitro of all 13 phenolic glycosides was evaluated against lipopolysaccharide-induced mouse macrophage RAW264.7 cells. The compounds 1, 9, and 10 potentially inhibited the productions of nitric oxide (NO), prostaglandin (PEG2), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6). Compound 1 (50 μM) showed stronger anti-inflammatory activity than Triptolide (TPL, 20 nm).

The spatial distribution of an air-gun array and the ghost reflection from the air-water interface cause a directional pattern of the source signature and introduce notches at certain frequencies. This significantly limits the bandwidth of the seismic data and the ability to obtain high-resolution subsurface imaging. With mathematical derivation and numerical simulation, we have determined that the inline directivity relies on the number of air guns and their spacing. Furthermore, the effective width of the take-off angles for an air-gun array is highly correlated with the reciprocal of the distance variance along the inline direction, which is subsequently used for optimizing the source design. For a normal horizontal source, one could adjust the distance between two consecutive air guns to improve the source signature. We optimize the spatial distribution for air guns along the inline and depth directions, that is, by using the synchronized multidepth stimulation mode, to minimize the inline directivity. Simulated results show that a six-gun composed multidepth source could be designed to achieve nearly identical energy distribution with up to ±30° take-off angle for the high-frequency end up to 250 Hz. This represents a significant improvement compared to a normal horizontal source and is more suitable for high-resolution seismic acquisition.

Phytochemical study of the twigs and leaves of Buxus rugulosa resulted in the isolation of eight triterpenoid alkaloids, including four new triterpenoid alkaloids, namely buxruguloids A–D (1–4), together with four known analogues 5–8. The structures of 1–4 were identified by the analysis of NMR and MS spectroscopic data. All the new compounds were assessed in vitro for their cytotoxic activities against five human tumor cell lines (HCT-116, HT-29, A549, MCF-7 and SW480). It turned out that compound 2 exhibited remarkable cytotoxic activities against these five cell lines with IC50 value ranged from 2.5–12.3 μM, respectively.

Background : Lots of plants in genus Swertia are widely used in the traditional medicine as the treatment for T2DM and its complications in Asia. However, the pharmacodynamic material basis and underlying mechanisms of these plants are still incompletely studied. Inhibition of aldose reductase to regulate polyol pathway is considered to be one effective strategy to treat many complications arising from diabetes. Aim : The inhibitory effect against aldose reductase of typical components from the genus Swertia were examined, and further verified in db/db mice model to explore its in vivo renal protective ability and underlying mechanism. Methods : Human recombinant aldose reductase (AR) was applied to detect the inhibitory activity of these components from genus Swetia in vitro, and the most active one was further analyzed in molecular docking experiment. Then, db/db diabetic mice model were employed to investigate the renal protective effects in vivo. Oxidative stress and renal function related indicators were determined using biochemical kit. Histopathological examination of kidney was conducted to evaluate pathological variations. RT-PCR was applied to measure the level of AR mRNA in renal cortex. Expression of AR, TGF-β1, Collagen Ⅳ, Nephrin and Podocin in kidney tissues were assessed by Western blot. Results : It turned out that demethylbellidifolin (DMB) showed the strongest inhibitory activity against AR, with an IC50 of 1.29 ± 0.16 μM, by stabilizing the active site of AR. In vivo experiment confirmed that DMB could remarkably reduce blood glucose and albuminuria level, and alleviate oxidative stress response. Meanwhile, histopathological examination also displayed that the kidney damage in db/db mice was significantly improved after treatment with DMB. Further mechanism study indicated that DMB could prevent the accumulation of sorbitol, one of the polyol pathway products. Besides, DMB could also maintaining the integrity of podocytes structure by up-regulating the expression of Nephrin and Podocin, and exert renal protective effects by inhibiting the expression of AR, Collagen Ⅳ and TGF-β1 in the polyol pathway. Conclusions : These findings indicated that genus Swertia could be an important plant sources of aldose reductase inhibitors, and one of its typical components, DMB, exerted a therapeutic role in the treatment of diabetic nephropathy by regulating the polyol pathway to relieve the injury of cells in the kidney, and may represent a promising renal protective medication for diabetic nephropathy therapy.

The root Rhynchosia volubilis was widely used for contraception in folk medicine, although its molecular mechanism on antifertility has not yet been revealed. In human sperm, it was reported that the cation channel of sperm, an indispensable cation channel for the fertilization process, could be regulated by various steroid-like compounds in plants. Interestingly, these nonphysiological ligands would also disturb the activation of the cation channel of sperm induced by progesterone. Therefore, this study aimed to explore whether the compounds in R. volubilis affect the physiological regulation of the cation channel of sperm. The bioguided isolation of the whole herb of R. volubilis has resulted in the novel discovery of five new prenylated isoflavonoids, rhynchones A – E (1 – 5), a new natural product, 5′-O-methylphaseolinisoflavan (6) (1H and 13C NMR data, Supporting Information), together with twelve known compounds (7 – 18). Their structures were established by extensive spectroscopic analyses and drawing a comparison with literature data, while their absolute configurations were determined by electronic circular dichroism calculations. The experiments of intracellular Ca2+ signals and patch clamping recordings showed that rhynchone A (1) significantly reduced cation channel of sperm activation by competing with progesterone. In conclusion, our findings indicat that rhynchone A might act as a contraceptive compound by impairing the activation of the cation channel of sperm and thus prevent fertilization.

Hanchuan Zupa Granule (HCZP) is a classic prescription of Uyghur medicine, that is used for cough and abnormal mucinous asthma caused by a cold and "Nai-Zi-Lai".This study aimed to explore the possible molecular mechanism of HCZP in the treatment of asthma, using a network pharmacology method and in vivo experiments.First, we conducted qualitative analysis of the chemical composition of HCZP as a basis for network pharmacology analysis. Using network pharmacology tools, the possible signaling pathways of HCZP in the treatment of asthma were obtained. An OVA-sensitized asthma model was established, and HCZP was continuously administered for one week. BALF was collected for cell counting, and serum and lung tissues were collected to analyze the expression of IgE, IL-4, IL-5, IL-13 and IFN-γ. Hematoxylineosin (HE) staining was performed to assess the pathological changes in the lung tissues. Related protein expression in the lung tissues was analyzed by Western blotting for molecular mechanism exploration.Fifty-six chemical compounds were identified by UPLC Q-TOF MS. According to the network pharmacology results, 18 active compounds were identified among the 56 compounds, and 68 target genes of HCZP in the treatment of asthma were obtained. A total of 19 pathways were responsible for asthma (P 0.05) according to KEGG pathway analysis. In vivo results showed that OVA sensitivity induced increased respiratory system resistance and inflammatory responses, which included inflammatory cell infiltration and high levels of IgE, IL-4, IL-5 and IL-13 in serum and lung tissues. Furthermore, OVA upregulated p-PI3K, p-JNK and p-p38 expression in lung tissues. Moreover, HCZP treatment significantly downregulated respiratory system resistance, and the expression of IL-4, IL-5, IL-13 and IgE, as well as significantly improved inflammatory cell infiltration in lung tissues. Moreover, the protein expression of p-PI3K, p-JNK and p-p38 in lung tissues decreased after HCZP treatment.HCZP significantly inhibited the OVA-induced inflammatory response via the PI3K-Akt and Fc epsilon RI signaling pathways.

Buxaustroines A-N (1-14), a series of triterpenoidal alkaloids featuring a novel 17(13→18)abeo motif, were obtained from the extract of Buxus austro-yunnanensis. Their structures were assigned based on NMR data analysis and X-ray diffraction crystallography. A putative biosynthetic pathway for one of the alkaloids from a co-isolate 15 is proposed. In the assessment of their bioactivities, some of the compounds displayed protective effects against doxorubicin-induced injury of myocardial cells. Preliminary structure-activity relationship studies of 1-14, which are based on the same skeleton, were conducted.

Xiao Ke Yin Shui (XKYS) formula is a traditional Chinese medicine formula treating type 2 diabetes mellitus (T2DM). XKYS formula consists of four herbs, i.e., Coptidis rhizoma, Liriopes radix, bitter melon, and Cassiae semen. Herein, the chemical profiles of four herb extracts were investigated, and further analysis of the underlying mechanism of XKYS formula treating T2DM was performed using network pharmacology. The main components were selected for our network-based research. Targets of XKYS formula were mainly collected from two databases, SwissTargetPrediction and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the text-mining method was also implemented. T2DM relating genes and therapeutic targets were collected from five databases. Subsequently, STRING and Cytoscape were employed for the analysis of protein-protein interaction (PPI) networks. Functional annotation and pathway analysis were conducted to investigate the functions and relating pathways of target genes. The content of 12 compounds in the herb extracts was determined. With the analysis of PPI networks, a total of 76 genes were found to be important nodes and could be defined as the main target genes regulated by XKYS formula in the treatment of T2DM and its complications. Components in XKYS formula mainly regulate proteins including protein kinase B (Akt), phosphatidylinositol 3-kinase (PI3K), insulin receptor substrate (IRS), and tumor necrosis factor (TNF). XKYS formula exerts therapeutic effects in a synergetic manner and exhibits antidiabetic effect mainly via reducing insulin resistance. These findings could be guidelines in the further investigation of this formula.

Purpose This paper investigates the relationship between product market competition and firms’ water information disclosure and how firms’ ownership type can affect this relationship in China, offering new insights into corporate water management. Design/methodology/approach The authors investigated 303 Chinese listed companies in highly water-sensitive industries to examine how product market competition influences corporate water information disclosure by subdividing the product market competition into market competition at the firm level and the industry competition intensity at the industry level. Findings The results show that there exists an inverted U-shaped relationship between industry competition and water information disclosure; enterprises with the highest market power in a mildly competitive industry are more willing to voluntarily disclose water information and play an industry benchmarking role. Further tests demonstrate that the relationship between industry competition intensity and water information disclosure is stronger for state-owned enterprises than for private enterprises. Research limitations/implications The current water resources regulations in China are relatively lax and the water risk awareness of firms is weak, which may affect the applicability of the results. In addition, water information disclosure research is a relatively new field and a quantitative index system for water information disclosure is still in the exploratory stage. Further developments, including the selection, definition and measuring methods of a water index are required. Practical implications The authors developed a new direction of enterprise water management activities from the perspective of market competition. Based on the market conditions in China, the authors also investigated the impact of the ownership type of the enterprises on the relationship between market competition and water information disclosure. Social implications The authors suggested that the government should improve laws and regulations and adopt incentive mechanisms to encourage enterprises to implement water resource management. In addition, the government should encourage high market status enterprises to actively fulfill their environmental responsibilities so that the entire industry is encouraged to follow suit. Originality/value This study represents an important development in the field of environmental accounting and is the first research on corporate water information disclosure; it also extends the research on the influence mechanisms of market competition on the environmental management practices of enterprises.

Thirteen previously undescribed guaiane-type sesquiterpenoids based on [5,7] bicyclic system, stelleranoids A–M (1–13), along with six known analogues (14–20), were isolated from the roots of Stellera chamaejasme with chromatographic techniques. Their structures including absolute configurations were determined by HRESIMS and spectroscopic data, quantum chemical calculations, as well as X-ray crystallographic analysis. Cytotoxicity test in three cell lines indicated that compound 14 had relatively stronger cytotoxic effect against MKN-45, SKOV3, and Du145 cell lines with IC50 of 9.8, 17.4 and 7.3 μM, respectively; compounds 3 and 8 displayed moderate cytotoxic effect against MKN-45 and Du145 cell lines with IC50 ranged from 14.5 to 18.8 μM, comparable to those of the positive control. As determined by fluorescent microscopy and flow cytometry in Du145 cell line, compound 14 could promote cell apoptosis and cause cell cycle arrest at the G0/G1 phase, leading to the inhibition of cell proliferation. Further Western blot analysis revealed that this inhibitory effect was accompanied by upregulating pro-apoptosis proteins cleaved-PARP, cleaved-Caspase-9 and tumor suppressor protein p53 while downregulating anti-apoptotic protein Bcl-2 in 14-treated Du145 cells.

Type 2 diabetic mellitus (T2DM), often accompanied by disorders of glucose and lipid metabolism, has troubled hundreds of millions of people. Xiaokeyinshui extract combination (XEC), derived from traditional Chinese medicines formula, has exerted hypoglycemic effects against T2DM. However, its mechanism of metabolic level is still unclear. In this study, a T2DM mice model, induced by a high sucrose/high fat diet combined with low-dose streptozotocin (STZ) injections, was adopted. The biochemical index was determined and a combination of metabolomics and lipidomics analyses of plasma were performed. The results showed that XEC increased secretion of insulin and level of HDL-C, decreased levels of FBG, HbA1c, TC, TG, LDL-C and repaired islet structure in diabetic mice. In addition, the metabolic profiles of plasma were analyzed and 54 potential biomarkers were screened out, mainly including carbohydrates, lipids and amino acids. These potential biomarkers were found to be correlated with the following pathways: galactose metabolism, fructose and mannose metabolism, TCA cycle, arachidonic acid metabolism, glycerolipid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and amino acid metabolism. In conclusion, we speculated that carbohydrate metabolism, lipid metabolism and amino acid metabolism played roles in the therapeutic mechanisms of XEC on T2DM.

In this study, C57BL/6J mice with high-fat diet- (HFD-) induced hyperlipidemia were treated with total Liriope spicata var. prolifera polysaccharides (TLSP: 200, 400, and 800 mg/kg body weight), simvastatin (3 mg/kg body weight), or saline for 8 weeks, respectively. The results showed that TLSP had strong lipid-lowering and hepatoprotective effects on C57BL/6J mice with HFD-induced hyperlipidemia. TLSP administration significantly reduced serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels and downregulated the expressions of peroxisome proliferator-activated receptor (PPAR)γ and fatty acid synthase (FAS) in the adipose and liver tissues of the mice. TLSP exerted hypolipidemic and hepatoprotective effects by activating lipid/bile acid metabolism via the FXH-SHP/CYP7A1 and SEBP-1c/FAC/ACC signaling pathways. Thus, TLPS is a promising natural polymer with hepatoprotective and hypolipidemic properties.

Extensive phytochemical study of the methanol extract of twigs and leaves of Buxus sempervirens resulted in the identification of 17 Buxus alkaloids, including 12 new ones, namely buxusemines A-L (1-12). Their structures were delineated by detailed analysis of the HRESIMS and NMR data, as well as quantum chemical NMR calculations. Buxusemine A (1) represents the second Buxus alkaloid with a unique spiro[4.6]undecatriene moiety, buxusemines B-C (2-3) are a rarely occurring class of Buxus alkaloids featured with an additional five-membered ring through the ether or lactone linkage between C-10 and C-23, and buxusemines D-F (4-6) are another rare type of Buxus alkaloids with an epoxy motif. In the assessment of their bioactivities, buxusemine F (6) and buxanoldine (17) displayed more potent protective effects than the positive control cyclovirobuxinum D in the doxorubicin-induced cardiac injury model.

Xiaokeyinshui (XKYS) formula, an anti-diabetic formula, was recorded in many ancient Chinese medical books. Xiaokeyinshui extract combination (XEC) originated from this ancient formula, consisting extracts of four herbal drugs, namely, Coptidis Rhizoma, Liriopes Radix, bitter melon, and Cassiae Semen.Therapeutic effects of Xiaokeyinshui extract combination (XEC) were assessed on diabetic rats.Herb extracts were prepared and mixed, yielding XEC. XEC were intragastrically given at doses of 260, 380 and 500 mg/kg/d to diabetic rats for 60 days. Anti-diabetic effects of XEC were studied, with measurement of body weight, and assessment of both glycemic control and lipid management. Measurement of oxidative stress and inflammatory cytokines were conducted in accordance to protocols of commercial kits. Parameters related to renal functions were also measured. Western blot (WB) analysis was performed to explore the anti-diabetic and renal protective mechanisms of XEC.Compared to diabetic control, XEC exhibited significant effects in both glucose-lowering and lipid management (p 0.01). Both oxidative stress and inflammatory cytokines were reduced after treatment of XEC for two months. In addition, XEC exhibited renal protective effects. WB analysis of liver tissue demonstrated that XEC achieved anti-diabetic effects through up-regulation of InsRα/IRS-1/PI3K/Akt/GLUT4 signaling pathway and phosphorylation of AMPK. In addition, renal protective effects were also achieved with down-regulation of RAGE and VEGF expressions in kidney.XEC exerts promising anti-diabetic and renal protective effects on diabetic rats in multi-target mechanisms. XEC could be a satisfying alternative treating T2DM and preventing diabetic nephropathy.

Using the data of Chinese industrial enterprises, we examine how the incentive to reach GDP growth targets affects the local firms' capacity utilization. We find that Chinese economic growth targets exhibit a persistent pattern of top-down amplification along different jurisdiction levels, which is associated with a decline in local firms' capacity utilization. Moreover, the effect of amplified targets on overcapacity is more pronounced (1) when officials utilize hard-constraint vocabulary in setting the economic growth target, (2) during the National Congress of Communist Party, and (3) when the age of prefecture-level officials is close to 55. We also find officials intervene local firms' capacity decisions by increasing private communication with local entities and loosening public policies for local firms within their jurisdictions. Further results show that the amplification of economic targets is detrimental to future development of both regional economy and local firms.

Snake bile is one of the most expensive traditional Chinese medicines (TCMs). However, due to the complicated constitutes of snake bile and the poor ultraviolet absorbance of some trace bile acids (BAs), effective analysis methods for snake bile acids were still unavailable, making it difficult to solve adulteration problems. In present study, ultrahigh-performance liquid chromatography with triple quadrupole linear ion trap mass spectrometry (UHPLC-QqQ-MS/MS) was applied to conduct a quantitative analysis on snake BAs. The mass spectrometer was monitored in the negative ion mode, and multiple-reaction monitoring (MRM) program was used to determine the contents of BAs in snake bile. In all, 61 snake bile from 17 commonly used species of three families (Elapidae, Colubridae and Viperidae), along with five batches of commercial snake bile from four companies, were collected and detected. Nine components, Tauro-3α,12α-dihydroxy-7-oxo-5β-cholenoic acid (T1), Tauro-3α,7α,12α,23R-tetrahydroxy-5β-cholenoic acid (T2), taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), taurodeoxycholic acid (TDCA), cholic acid (CA), Tauro-3α,7α-dihydroxy-12-oxo-5β-cholenoic acid (T3), and Tauro-3α,7α,9α,16α-tetrahydroxy-5β-cholenoic acid (T4) were simultaneously and rapidly determined for the first time. In these BAs, T1 and T2, self-prepared with purity above 90%, were first reported with their quantitative determination, and the latter two (T3 and T4) were tentatively determined by quantitative analysis multi-components by single marker (QAMS) method for roughly estimating the components without reference. The developed method was validated with acceptable linearity (r2≥0.995), precision (RSD＜6.5%) and recovery (RSD＜7.5%). It turned out that the contents of BAs among different species were also significantly different; T1 was one of the principle bile acids in some common snake bile, and also was the characteristic one in Viperidae and Elapidae; T2 was the dominant components in Enhydris chinensis. This quantitative study of BAs in snake bile is a remarkable improvement for clarifying the bile acid compositions and evaluating the quality of snake bile.

Xiao Ke Yin Shui (XKYS) formula is a traditional Chinese medicine formula treating type 2 diabetes mellitus (T2DM). XKYS formula consists of four herbs, i.e., Coptidis rhizoma, Liriopes radix, bitter melon, and Cassiae semen. Herein, the chemical profiles of four herb extracts were investigated, and further analysis of the underlying mechanism of XKYS formula treating T2DM was performed using network pharmacology. The main components were selected for our network-based research. Targets of XKYS formula were mainly collected from two databases, SwissTargetPrediction and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the text-mining method was also implemented. T2DM relating genes and therapeutic targets were collected from five databases. Subsequently, STRING and Cytoscape were employed for the analysis of protein-protein interaction (PPI) networks. Functional annotation and pathway analysis were conducted to investigate the functions and relating pathways of target genes. The content of 12 compounds in the herb extracts was determined. With the analysis of PPI networks, a total of 76 genes were found to be important nodes and could be defined as the main target genes regulated by XKYS formula in the treatment of T2DM and its complications. Components in XKYS formula mainly regulate proteins including protein kinase B (Akt), phosphatidylinositol 3-kinase (PI3K), insulin receptor substrate (IRS), and tumor necrosis factor (TNF). XKYS formula exerts therapeutic effects in a synergetic manner and exhibits antidiabetic effect mainly via reducing insulin resistance. These findings could be guidelines in the further investigation of this formula.

Cassiae Semen, the dried seed of Cassia obtusifolia L. (Leguminosae), is a traditional Chinese medicine. It has long been used as the treatment of diabetic hyperlipidemia and diabetic constipation in Traditional Chinese Medicine formulae.The present study was designed to investigate the anti-diabetic and renoprotective effects of Cassiae Semen extract (CSE) in streptozotocin (STZ)-induced diabetic rats.Quality control of CSE was performed using HPLC. CSE were orally administered at 27, 54 and 81 mg/kg dose to high-sucrose-high-fat (HSHF) diet and STZ-induced diabetic rats for 60 days. Body weight, glucose metabolism and lipid metabolism profiles were measured to assess the anti-diabetic effect of CSE. Oxidative stress markers and inflammatory factors were determined using commercial kits. Renal function related parameters were also measured. Histopathological examination of kidney was conducted for the validation of pathological changes in the diabetic rats. Immunohistochemical examination of kidney was measured to investigate the expression of RAGE in renal tissues.Five compounds, including two anthraquinones and three naphtopyrones were simultaneously determined in CSE. Compared with diabetic control, groups treated with CSE exhibited an anti-diabetic effect, including a significant amelioration in body weight, glycemic control, oral glucose tolerance and lipid metabolism (P 0.01). Moreover, oxidative stress and inflammatory responses decreased after oral administration of CSE (P 0.01). CSE also showed protective effects on renal functions, decreasing the ratio of kidney/body weight, 24 h urine volume, 24 h urine protein, serum creatinine (Scr) and blood urea nitrogen (BUN) (P 0.01). Additionally, renal protective effect was also observed in histopathological examination. Immunohistochemical analysis showed that CSE downregulated the expression of RAGE.It turned out that CSE had both anti-diabetic and renoprotective effects in diabetic rats. CSE can be a potential agent in the treatment of type 2 diabetes mellitus (T2DM) and its complications.

Snake bile, a precious traditional Chinese medicine (TCM), was used as the major ingredient of some Chinese patent drugs, such as Shedan Chuanbei powder and Shedan Chenpi powder for hundred years. However, there is still requirement for the comprehensive and definite composition of bile acids in snake bile. In order to rapidly identify the bile acids constituents in snake bile to avoid the adulteration, ultrahigh-performance liquid chromatography with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC/ESI-QTOF-MS/MS) has been applied to conduct a qualitative analysis on snake bile acids. ESI ion source was used for mass spectra, and data were collected in both positive and negative ion mode. 16 kinds of reference standards, attributed to free bile acids, taurine- and glycine- conjugated bile acids, were detected and their MS behaviors were summarized. In negative ion mode, the diagnostic ions of free bile acids were obtained via the neutral losses of H2O and CO2 molecules; the diagnostic ions of taurine-conjugated bile acids were at m/z 124.0068 ([C2H6NO3S]-), m/z 106.9803 ([C2H3O3S]-) and m/z 79.9568 ([SO3]-); the diagnostic ion of glycine-conjugated bile acids was at m/z 74.0242 ([C2H4NO2]-). In positive ion mode, dehydration ions, amide bond cleavage ions, and reversed Diels-Alder at A-ring ions were detected in every kind of reference. These reference MS behaviors were used for identifying bile acids without reference standards in snake bile. As a result, totally 15 compounds, including 4 pairs of isomers, were identified by comparing the retention time, exact molecular mass and fragmentation behaviors with reference standards, respectively. Tauro-3β,7α,12α-trihydroxy-5β-cholenoic acid, Tauro-△8-3β,7α,12α- trihydroxy-5β-cholenoic acid, Tauro-3α,7α,12α,23R-tetrahydroxy-5β-cholenoic acid, and Tauro-3α,7α-dihydroxy-12-oxo-5β-cholenoic acid, Taurocholic acid, Glycocholic acid, Taurochenodeoxycholic acid, Taurodeoxycholic acid and Cholic acid were detected as the common bile acids in snake bile. Tauro-△8-3β,7α,12α-trihydroxy-5β-cholenoic acid, Tauro-3α,7α,9α,16α-tetrahydroxy-5β-cholenoic acid, Tauro-3α,12α,17R,22R-tetrahydroxy-5β-cholenoic acid, and Tauro-△1,8-3β,7β,12α-trihydroxy-5β-cholenoic acid were firstly reported in this study.

The unconventional photoluminescence of sulfonated acetone–formaldehyde (SAF) and acetone–formaldehyde (AF) condensates are uncovered and studied in this work. Their fluorescence had been ignored although they were developed and commercialized as water reducing agents in the concrete industry decades ago. More importantly, based on the traditional mechanism of the Mannich reaction, sulfonated ethylenediamine–acetone–formaldehyde (SEAF) was successfully synthesized by introducing imino groups to SAF. It shows highly enhanced fluorescence both in solution and the solid state. The emission mechanism of these polymers is proposed to be via the cluster of carbonyl groups within the long linear nonconjugated chain. Hydroxy, sulfonic and amino groups in SEAF can produce strong ionic and hydrogen bonds, which contribute to its fluorescent enhancement. Furthermore, it is more interesting that SAF and SEAF possess an aggregation-enhanced emission (AEE) effect, while AF shows aggregation-caused quenching (ACQ). This result confirms the previous report that hydrogen bonds can induce AEE effects. Our study provides a novel perspective for the design of water-soluble luminescent materials with green photoluminescence and AEE property.

This dataset is supplementary to our accepted article in Journal of Ethnopharmacology [1]. Xiaokeyinshui (XKYS) formula, an anti-diabetic formula, was recorded in many ancient Chinese medical books. Xiaokeyinshui extract combination (XEC) originated from this ancient formula, consisting extracts of four herbal drugs, i.e., Coptidis Rhizoma, Liriopes Radix, bitter melon, and Cassiae Semen. In this study, herb extracts were prepared and mixed, producing Xiaokeyinshui extract combination (XEC). The optimized formula of XEC was also investigated via uniform experimental design. Diabetes was induced in Kunming mice, using high-sugar-high-fat diet combined with injection of streptozotocin (STZ) intraperitoneally. Different formulae of XEC were intragastrically administered to diabetic mice for 28 days. Fasting blood glucose (FBG), oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), total cholesterol (TC), total triglyceride (TG) were measured to assess the anti-diabetic effects of each formula. Multivariate second degree polynomial model was applied in the fitting of metabolic parameters, and the extremum value of each regression model was calculated using grid algorithm. In addition, an optimized formula of XEC was subjected to validation experiment in mice model. This data could provide basis for a reasonable analysis for the optimization of the formula of XEC.

Ethnopharmacological relevance Circaea mollis Sieb. & Zucc., a genus of Circaea that follows Onagraceae, has been used for centuries as a folk herb in traditional Chinese medicine (TCM) and Hani Ethnopharmacy for the treatment of joint swelling and pain in rheumatoid arthritis. Aim of the study This study was designed to confirm anti-arthritic effects and its underlying mechanism of ethanol extracts of Circaea mollis Sieb. & Zucc. (EEC), which may contribute to provide the pharmacological basis in the treatment of rheumatoid disease. Materials and methods Dimethylbenzene (DMB)-induced inflammatory swelling model, hot-plate pain model in mice and Freund's complete adjuvant (FCA)-induced arthritis model in rats were used to evaluate the anti-arthritis effect of EEC. Arthritis severity was done by measuring inflammatory swelling, pain threshol, paw swelling, arthritis index, body weight, spleen index and thymus index. The levels of TNF-α, IL-1β and IL-10 in sera were measured using ELISA. The pathological change of the ankle joint was also done. Phenolic composition of EEC was analyzed. Results EEC inhibited inflammatory swelling and increased heat-induced pain threshold in mice. Furthermore, EEC significantly alleviated paw swelling and arthritis index, decreasing the spleen index and thymus index. Besides, EEC down-regulated the serum TNF-α and IL-1β, and increased the production of serum IL-10 in FCA-induced rats. Histopathological examination demonstrated that EEC can effectively relieve synovial hyperplasia, control the infiltration of the inflammatory and protect cartilage from destruction. Conclusion Our work demonstrated that EEC possessed the potential therapeutic effect against arthritis in rodents which was attributed to modulating proinflammatory cytokines TNF-α, IL-1β and anti-inflammatory factors IL-10. Flavonoids and polyphenols may contribute to the therapeutic effect of EEC on arthritis.

Ampelopsis grossedentata, an indigenous plant in southern China, has been used for treating pharyngitis in traditional Chinese medicine for hundreds of years. In this study, we explored the anti-inflammatory activity of dihydromyricetin (1), its major bioactive component, and the underlying mechanism of this action. We demonstrated that 1 suppressed the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) as well as increased the level of the anti-inflammatory cytokine interleukin-10 (IL-10) in lipopolysaccharide (LPS)-treated mice. Moreover, 1 was found to markedly inhibit the production of nitric oxide (NO) and the levels of TNF-α, IL-1β, and IL-6, whereas it increased the level of IL-10 in LPS-induced RAW 264.7 macrophage cells. Compound 1 also reduced the protein expression of inducible nitric oxide synthase (iNOS), TNF-α, and cyclooxygenase-2 (COX-2) in macrophage cells. Furthermore, 1 suppressed the phosphorylation of NF-kappa B (NF-κB) and IκBα as well as the phosphorylation of p38 and JNK but not ERK1/2 in LPS-stimulated macrophages. Taken together, the present results suggest that 1 exerts its topical anti-inflammatory action through suppressing the activation of NF-κB and the phosphorylation of p38 and JNK. Thus, 1 may be a potentially useful therapeutic agent for inflammatory-related diseases.

This paper used relevant research of capital structure as reference in consideration of strategic emerging industry, pointed put forward nine hypotheses. The samples of the empirical research are 224 listed enterprises from Shanghai and Shenzhen stock markets in the year 2012. The research showed that trade factor had influence on capital structure, and profitability was the key influence factor. Besides, firm size, growth and asset liquidity were also the influence factors.

Snake gallbladder, a traditional Chinese medicine, has been believed in various Asian countries to improve visual acuity and alleviate rheumatism. Bile acids, a major component of the gallbladder, are toxic to the liver and kidney in humans and animals due to its detergent effects, while also exhibiting therapeutic effects due to an increase in the gallbladder contractions of muscle strips in patients with cholesterol gallstones. Secretion of bile acids in human and mammals depends on the bile salt export pump (BSEP), a liver-specific adenosine triphosphate (ATP)-binding cassette transporter encoded by ABCB11. However, the presence of BSEP in snakes has not been thoroughly explored. Here we confirm the existence of BSEP and its coding DNA sequence in snakes on both the proteomic and genetic level. This work provides information on the snake ABCB11 sequence and helps further potential genetic manipulation to affect bile salt metabolism. Our study provides the foundation for research on bile acid production from snakes by using modern genetic and proteomic methodologies.

The natural product mangiferin (compound 7) has been identified as a potential glucokinase activator by structure-based virtual ligand screening. It was proved by enzyme activation experiment and cell-based assays in vitro, with potency in micromolar range. Meanwhile, this compound showed good antihyperglycemic activity in db/db mice without obvious side effects such as excessive hypoglycaemia.

Structures and in vitro hypoglycemic activities of polysaccharides from different species of Maidong were studied. The primary structures of polysaccharides were elucidated on the basis of GC, GC-MS, infrared, NMR and periodate oxidation-Smith degradation. Liriope spicata polysaccharide (LSP), Ophiopogon japonicus polysaccharide (OJP) and Liriope muscari polysaccharide (LMP) were composed of β-fructose and α-glucose. The average molecular weights of LSP, OJP and LMP were 4742, 4925 and 4138Da with polydispersity indexes of 1.1, 1.2 and 1.1, respectively. The backbones of polysaccharides were formed by Fruf-(2→, →2)-Fruf-(6→, →6)-Glcp-(1→ and →1, 2)-Fruf-(6→ with a molar ratio of 5.0:18.2:1.0:5.3 (LSP), 6.8:15.8:1.0:5.8 (OJP), 8.3:12.3:1.0:3.9 (LMP), respectively. The RT-PCR and western blot analysis indicated that LSP, LMP and OJP increased the expression of PI3K, AKT, InsR, PPARγ and decreased the expression of PTP1B in mRNA level and protein level in IR HepG2 cells. Furthermore, glucose consumption was increased after treated with polysaccharides. These results revealed that LSP, OJP and LMP had potential anti-diabetic effects.

Ethnopharmacological relevance Swertia macrosperma is a traditional folk medicine used for its anti-hepatitis, antipyretic and antidotal effects as “Dida” or “Zangyinchen” in Tibet, Yunnan and Guizhou province for a long time, and it has been reported for its anti-diabetic effects in a Chinese patent. Swertia macrosperma was reported rich in xanthones, iridoids, seco-iridoids and their glycosides, several of which had been documented as potential antidiabetic agents. The objective of this study was to investigate the antidiabetic effect of Swertia macrosperma in diabetic rats. Materials and methods This study was designed firstly to evaluate the effect of Swertia macrosperma on glucose consumption in HepG2 cells. Based on the result in HepG2 cells, the antidiabetic effect of ethanol extract (EE) and n-butanol extract (BE) were investigated in diabetic rats induced by high fat fed and streptozotocin. The effects of EE and BE on fasting blood glucose, oral glucose tolerance test, serum insulin, glycosylated hemoglobin, serum lipid level, serum antioxidant parameters, glucokinase, glucose-6-phosphatase activities and glycogen content in liver tissue were measured, histology examination of pancreatic tissue was also carried out. Results After 4 weeks treatment with EE and BE, apparently decreased fasting blood glucose concentrations were observed in these treated groups, compared with the diabetic control groups. Additionally, improvement in serum antioxidant parameters and lipid profile were evidenced clearly. Moreover, EE and BE had effects of protecting the pancreatic β-cells and stimulating insulin secretion from the remaining pancreatic β-cells, evidenced by pancreatic histology examination. Increased glucokinase activity and decreased glucose-6-phosphatase activity were observed in liver. Conclusion The results of in vivo and in vitro experiment suggested that EE and BE of Swertia macrosperma had excellent effects on controlling the hyperglycemia and hyperlipidemia in diabetic rats.

BACKGROUND Liriopes Radix, which is regarded as both drug and healthy diet, is drunk as tea and used in traditional Chinese medicine to treat diabetes. Based on our previous studies, investigated the hypoglycemic effects and explored the mechanisms of total polysaccharides from Liriope spicata var. prolifera (Liriopes Radix) in a diabetic rat model. RESULTS TLSP reduced hyperglycemia in diabetic rats. The oral glucose tolerance test showed that TLSP could improve the glucose tolerance of diabetic rats. Damage to liver and pancreas tissue was inhibited after treatment with TLSP. Moreover, TLSP increased glycogen content, glucokinase (GK) and glycogen synthetase (GS) activities, and suppressed the elevation of glucose-6-phosphatase (G6Pase) and glycogen phosphorylase (GP) activities in liver. Compared with the diabetic control group, GK and GS mRNA expression were significantly elevated, while G6Pase and GP mRNA expression were decreased in TLSP groups. In addition, TLSP could inhibit glycogen synthase kinase-3β expression and increase insulin receptor, insulin receptor substrate-1, phosphoinositide 3-kinase, protein kinase B and glucose transport protein-4 expression in liver. CONCLUSION TLSP showed hypoglycemic function. Improvement of glucose metabolism and insulin-signaling transduction were possible mechanisms. © 2013 Society of Chemical Industry

The direct compression (DC) technology is increasingly popular in the manufacture of tablets due to its efficiency and economy. However, its use in the production of Traditional Chinese Medicine (TCM) tablets is often limited owing to poor powder flow and compaction properties of TCM powders. In this work, we aimed at improving properties of powders used in Fufang Danshen tablet, a popular TCM for treating angina pectoris, by particle surface engineering. Both the active ingredients (Danshen root, Notoginseng, and Borneol) and formulated Danshen mixture exhibit flowability too poor to be processed directly on a high speed tablet press. By dry coating with 1% silica nanoparticles, the flowability, tabletability, and fillability of these powders were adequately improved to be suitable for DC.

Ethnopharmacological relevance Swertia kouitchensis has long been used as a folk medicine to treat hepatitis and diabetes in central-western China. Therefore, this study was aimed to evaluate the anti-diabetic activity of the plant ethanol extract. Materials and methods Firstly, the extract was tested for its inhibitory activity on α-amylase and α-glucosidase in vitro. Following that, insulin secretion test in NIT-1cell was performed. Then, oral sucrose or starch tolerance test of the extract were carried out in normal mice. After that, acute effect of the extract was executed in normal and streptozotocin-induced (60 mg/kg) diabetic mice. Eventually, long term effect of the extract was performed in diabetic mice for 4 weeks. Oral glucose tolerance test and biochemical parameters were estimated at the end of the study. Results Swertia kouitchensis extract could remarkably inhibit the activity of α-amylase and α-glucosidase and stimulate insulin secretion in vitro. And also the extract displayed anti-hyperglycemic activity, improved antioxidant capacity, ameliorated the hyperlipidemia and carbohydrate metabolism in diabetic mice. Conclusions Swertia kouitchensis exhibits considerable anti-diabetic activity and metabolic alterations in diabetic mice. These results provide a rationale for the use of Swertia kouitchensis to treat diabetes mellitus.

The dried stems of Schisandra henryi var. henryi were extracted with 95% ethanol and the extracts were further subjected to partition, affording the ethyl acetate extracts(EtOAc Extrs.).The EtOAc Extrs.were separated and purified with silica gel and octadecyl-silylated silica gel column chromatography, preparative HPLC and preparative TLC. Thirteen known compounds were obtained and identified by spectral methods including MS and NMR, all of which were elucidated as t-cadinol(1), cadinane-4β,5α,10β-triol(2), cadinane-5α, 10α-diol-2-ene(3), oxyphyllenodiols A(4), 1β, 4β-dihydroxyeudesman-11-ene(5), cyperusol C(6), (7R)-opposit-4(15)-ene-1β,7-diol(7), dysodensiol E(8), epi-guaidiol A(9), aromadendrane-4β,10β-diol(10), tricyclohumuladiol(11), caryolane-1,9β-diol(12), and guaidiol A(13). Compounds 3, 5-10, and 13 were separated from the genus for the first time, while compounds 1-13 were separated from this species for the first time.

CRISPR/Cas9 is a powerful genome editing tool that has been extensively used in model plants and crops, such as Arabidopsis thaliana, rice, wheat, and soybean. Here, we report the use of CRISPR/Cas9 to precisely knock out the committed diterpene synthase gene (SmCPS1) involved in tanshinone biosynthesis in Salvia miltiorrhiza, a traditional Chinese medicinal herb with significant pharmacological activities, such as vasorelaxation, protection against ischemia-reperfusion injury, and antiarrhythmic effects. Three homozygous and eight chimeric mutants were obtained from 26 independent transgenic hairy root lines by Agrobacterium rhizogenes-mediated transformation. The metabolomic analysis based on LC-qTOF-MS and Q-TRAP-LC-MS/MS revealed that tanshinones, especially cryptotanshinone, tanshinone IIA and tanshinone I, are completely missing in homozygous mutants, without influencing other phenolic acid metabolites. By contrast, tanshinones are decreased but still detectable in chimeric mutants, which is similar to a previously-reported an RNAi study of SmCPS1. These results demonstrate that Agrobacterium rhizogenes- mediated transformation using CRISPR/Cas9 is a simple and efficient genome editing tool in S. miltiorrhiza, thus paving the way for large-scale genome editing in S. miltiorrhiza, which is important for pathway elucidation of secondary metabolites, quality improvement, and yield increases for this valuable traditional Chinese medicinal herb.

Ethnopharmacological relevance\ud \ud Schisandra glaucescens Diels (SGD) is used in a subclass of traditional Chinese medicine known as “Tujia drugs”. It has been long used for the treatment of rheumatoid arthritis (RA), cough with dyspnea, spontaneous sweating, night sweating, chronic diarrhea, and neurasthenia. As a woody liana growing in mountain jungles at the altitudes of 750–1800 m, it is mainly distributed in Sichuan and Hubei Provinces of China.\ud \ud Aim of the study\ud \ud To evaluate the antiarthritic activity of acetate (EA) and n-butanol (Bu) fractions of SGD extract on a collagen-induced arthritis mice model.\ud \ud Materials and methods\ud \ud Acute toxicity of EA and Bu fractions of SGD extract was evaluated by gavage on normal mice. Pharmacological investigations were conducted on arthritis male Balb/c mice. The animal model was induced by immunization with type II bovine collagen (CII) on the 1st and the 14th day of the experimental schedule. EA fraction (104, 312, 936 mg/kg), Bu fraction (156, 469, 1407 mg/kg) of SGD extract was orally administered every two days since the 15th day for 3 weeks. Progression of edema in the paws was measured using a vernier caliper every 3 days since the 10th day. At the end of the experiment, the spleen index and histological changes of the hind knee joints were investigated. Additionally, to explore the possible antirheumatic mechanisms of the EA and Bu fractions, ELISA was carried out to analyze TNF-α, IL-10, IL-6 and IL-1β in the serum.\ud \ud Results\ud \ud The half lethal doses of both EA and Bu fractions were much higher than the dose administered in the pharmacological investigations. Oral administration of EA fraction and Bu fraction of SGD extract significantly and does-dependently inhibited type ІІ collagen induced arthritis (CIA) in mice, as indicated by the effects on paws swelling and spleen index. Histopathological examinations demonstrated that SGD effectively protected the bones and cartilages of knee joints from erosion, lesion and deformation. Besides, the serum concentrations of cytokines TNF-α, IL-1β and IL-6 were significantly lower than the ones from the vehicle control group. Respectively, while cytokine IL-10 was remarkably higher compare with the vehicle control group.\ud \ud Conclusions\ud \ud SGD might be a safe and effective candidate for the treatment of RA, and deserves further investigation on the chemical components in both EA and Bu fractions of SGD extract.

Two new flavan-4-ol glycosides, (2R,4S)-6,8-dimethyl-7-hydroxy-4′-methoxy-4,2″-oxidoflavan-5-O-β-d-6″-O-acetyl-glucopyranoside (1) and (2R,4S)-5,7-O-β-d-di-glucopyranosyloxy-4′-methoxy-6,8-dimethyl-4,2″-oxidoflavane (2), were isolated from the rhizomes of Abacopteris penangiana. Their structures were elucidated by spectroscopic methods. Compounds 1 and 2 showed significant anticancer activities against HeLa and L929 cell lines in vitro.

Our research on adverse effects of lead exposures on physical and neurobehavioral health of children aged 6-12years in 4 villages, labeled as K, M, L, and X, in rural China, was reported in this article. Lead in blood (PbB), urine (PbU), hairs (PbH), and nails (PbN) were measured by graphite furnace atomic absorption spectrometry. Abbreviated Symptom Questionnaire of Conner's instruments and Revised Raven's Standard Progressive Matrices were applied to evaluate childhood attention deficit/hyperactivity disorders (ADHD) and intelligences. Geometric means (SD) of PbB, PbU, PbH and PbN concentrations were 71.2 microg/L (1.56), 11.7 microg/g (1.75), 12.5 microg/g (2.82), and 25.3 microg/g (2.79), respectively. 54 (17.0%) children had PbB levels ofor =100 microg/L. Boys, 6-10 years old, and living in village K were 2.11, 2.48, and 9.16 times, respectively, more likely to be poisoned by lead than girls, aged 11-12 years, and residing in X. 18 (5.7%) and 37 (11.7%) subjects had ADHD and mental retardations, respectively. Inverse relationships between intelligences and natural log transformed PbU and PbH levels were observed with respective odds ratios (95%CI) of 1.79 (1.00-3.22) and 1.46 (1.06-2.03) or 1.28 (1.04-1.58) and 1.73 (1.18-2.52) by binary or ordinal logistic regression modeling. ADHD prevalence was different by gender and age of subjects. PbU, PbH, and PbN related to PbB positively with respective correlation coefficients of 0.530, 0.477, and 0.181. Receiver operating characteristic (ROC) curves of the three measurements revealed areas under curves (AUCs) being 0.829, 0.758, and 0.687, respectively. In conclusion, children had moderate levels of lead exposures in this rural area. Intelligence declines were associated with internal lead levels among children. ROC analysis suggests PbU an internal lead indicator close to PbB.

Karyotype of Liriope spicata var. prolifera, a Chinese endemic species, was described in detail for the first time. Its proto-variety L. spicata was also investigated for comparison. The basic chromosome number of these two species was x = 18. L. spicata var. prolifera, recorded as triploid 2n = 54, consisted of 30 metacentric chromosomes and 24 submetacentric chromosomes. Only one chromosome of the 11th group had a secondary constriction with a satellite in the short arm. L. Spicata was tetraploid 2n = 72 and consisted of four sets of 6 submetacentric chromosomes and 12 metacentric chromosomes without visible satellites. This paper provides further available data on Liriope chromosomes, and also indicates that L. spicata var. prolifera and L. spicata are probably separate species.