Mechanochemical preparation of triptolide-loaded self-micelle solid dispersion with enhanced oral bioavailability and improved anti-tumor activity.

Triptolide (TP), a compound isolated from a Chinese medicinal herb, possesses potent anti-tumor, immunosuppressive, and anti-inflammatory properties, but was clinically limited due to its poor solubility, bioavailability, and toxicity. Considering the environment-friendly, low-cost mechanochemical techniques and potential dissolution enhancement ability of Na2GA, an amorphous solid dispersion (Na2GA&TP-BM) consisting of TP and Na2GA were well-prepared to address these issues. The performance of Na2GA&TP-BM was improved through ball milling, such as from crystalline state to an amorphous solid dispersion, suitable nano micelle size and surface potential, and increased solubility. This change had a significant improvement of pharmacokinetic behavior in mice and could be able to extend the blood circulation time of the antitumor drug. Moreover, in vitro and in vivo anti-tumor study showed that Na2GA&TP-BM displayed more potent cytotoxicity to tumor cells. The work illustrated an environment-friendly and safe preparation of the TP formulation, which was promising to enhance the oral bioavailability and antitumor ability of TP, might be considered for efficient anticancer therapy.

Multipeak Coercive Electric-Field-Based Multilevel Cell Nonvolatile Memory With Antiferroelectric-Ferroelectric Field-Effect Transistors (FETs).

An ultralow program/erase voltage ( |VP/E| = 4 V) is demonstrated by using an antiferroelectric-ferroelectric field-effect transistor (AFE-FE-FET) through a multipeak coercive E -field ( EC ) concept for a four-level stable state with outstanding endurance (>105 cycles) and data retention (>104 s at 65 °C). The mixture of ferroelectric (FE) and AFE domains can provide stable multistate and data storage with zero bias for multilevel cell (MLC) applications. HfZrO2 (HZO) with AFE-FE assembles an orthorhombic/tetragonal (o/t) phase composition and is achieved by [Zr] modulation in an HZO system. MLC characteristics not only improve high-density nonvolatile memory (NVM) but are also beneficial to neuromorphic device applications.

Arsenic Trioxide Cooperate Cryptotanshinone Exerts Antitumor Effect by Medicating Macrophage Polarization through Glycolysis.

Hepatocellular carcinoma (HCC) is an often-fatal malignant tumor with high lethality. Despite advances and significant efficacy in monotherapy, cancer therapy continues to pose several challenges. Novel combination regimens are an emerging strategy for anti-HCC and have demonstrated to be effective. Here, we propose a potential combination for HCC treatment named arsenic trioxide cooperate cryptotanshinone (ACCS). A remarkable synergistic therapeutic effect has been achieved compared with drugs alone in both in vivo and in vitro experiments. Mechanism study indicated that ACCS exerts its therapeutic actions by regulating macrophage-related immunity and glycolysis. ACCS potentiates the polarization of M1 macrophages and elevates the proportion of M1/M2 to remodel tumor immunity. Further molecular mechanism study revealed that ACCS intensifies the glucose utilization and glycolysis in the macrophage by increasing the phosphorylation of AMPK to activating the AMPK singling pathway. In conclusion, ACCS is a highly potential combination regimen for HCC treatment. The therapeutic potential of ACCS as a candidate option for anticancer drugs in restoring the balance of immunity and metabolism deserves further investigation.

Unipolar Parity of Ferroelectric-Antiferroelectric Characterized by Junction Current in Crystalline Phase Hf1-xZrxO2 Diodes.

Ferroelectric (FE) Hf1-xZrxO2 is a potential candidate for emerging memory in artificial intelligence (AI) and neuromorphic computation due to its non-volatility for data storage with natural bi-stable characteristics. This study experimentally characterizes and demonstrates the FE and antiferroelectric (AFE) material properties, which are modulated from doped Zr incorporated in the HfO2-system, with a diode-junction current for memory operations. Unipolar operations on one of the two hysteretic polarization branch loops of the mixed FE and AFE material give a low program voltage of 3 V with an ON/OFF ratio >100. This also benefits the switching endurance, which reaches >109 cycles. A model based on the polarization switching and tunneling mechanisms is revealed in the (A)FE diode to explain the bipolar and unipolar sweeps. In addition, the proposed FE-AFE diode with Hf1-xZrxO2 has a superior cycling endurance and lower stimulation voltage compared to perovskite FE-diodes due to its scaling capability for resistive FE memory devices.

[Study on anti-hyperlipidemia effect of Linderae Radix via regulating reverse cholesterol transport].

This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.

Cytochrome P450 2A6 is associated with macrophage polarization and is a potential biomarker for hepatocellular carcinoma.

Cytochrome P450 2A6 (CYP2A6) is an important metabolic enzyme and is involved in the progression of hepatocellular carcinoma (HCC). However, its specific function and the mechanism of modulation remain to be elucidated. In this study, we found that CYP2A6 is dramatically downregulated in HCC. CYP2A6 expression is closely associated with pathological grading, histologic grade, hepatitis, vascular metastasis, liver inflammation, and worse prognosis. Reduced expression of CYP2A6 contributes to alternative activation of macrophage polarization and impairs macrophage maturation and phagocytosis. Mechanistically, CYP2A6 participates in arachidonic acid metabolism, initiates 20-hydroxyeicosatetraenoic acid (HETE) generation, and inhibits epoxyeicosatrienoic acid (EET) generation. Disruption of the equilibrium between 20-HETE and EETs can induce macrophage polarization, thereby modulating antitumor immunity.

[Correlation between lipid-lowering efficacy and components of Pericarpium Citri Reticulatae].

Based on pharmacodynamics-component correlation analysis,the best effective part of hyperlipidemia of Pericarpium Citri Reticulatae( PCR) was screened out to confirm the possible constituents with the lipid regulating effect,in order to provide a basis for the development of new drugs. Hyperlipidemia rats induced by fat emulsion were used to screen out the best hypolipidemic parts of PCR with TC,LDL-c as the index. HPLC-ESI-MS were used to analyze common constituents of the different solvent extracts from PCR. The constituents were classified and identified based on the retention time,m/z and UV spectra. And the HPLC-DAD were used to determine the contents of flavonoids( narirutin,hesperidin,didymin,nobiletin,tangeretin,3,5,6,7,8,3',4'-heptemthoxyflavone).Correlation analysis was conducted on the constituents and efficacy with the method of SPSS ANOVA bivariate correlation. Five extracts could significantly decrease the content of TC,LDL-c of hyperlipemia rats induced by fat emulsion,and the best effective part were95% ethanol and ethyl acetate. There were 19 common peaks in five different solvent extracts from PCR,and 17 flavonoids were identified and classified,including 10 polymethoxyflavonoids and 7 other flavonoids. According to the raw material quantity,the order of content of flavonones arranged from high to low: n-butyl alcohol part> 95% ethanol part> water part> ethyl acetate part> petroleum ether part; and the order of PMFs arranged from high to low: n-butyl alcohol part≈95% ethanol part≈ethyl acetate part > petroleum ether part > water part. The decreased percentage of TC,LDL-c was positively correlated with 10 common PMFs constituents,which suggested that PMFs may be the effective components for reducing blood lipid.

The gene spectrum of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangdong province, China.

BACKGROUND: G6PD deficiency presents a higher incidence rate in southern China. Many variants of G6PD resulted from point mutations in the G6PD gene, which lead to decrease of enzyme activity. The objective of this study was to analyze the genotype of G6PD deficiency in four regions of Guangdong province. METHODS: Genotype of 1756 cases with G6PD deficiency was identified by reverse dot blotting (RDB). Unidentified Genotype of the samples was further ascertained by direct DNA sequencing. RESULTS: 34 genotype were found in 1756 cases of G6PD deficiency, Canton (c.1376 G>T) and Kaiping (c.1388 G>A) were the most common variants, accounting for more than 63% of G6PD deficiency individuals, and the following mutations were Gaohe (c.95 A>G), Chinese-5 (c.1024 C>T) and Chinese-4 (c.392 G>T). Two rare mutations Orisa (c.131 C>G) and IVS-5 637/638 T del have been discovered in this study. In addition, c.1311 C>T/IVS-1193 T>C polymorphism had a relatively high frequency in the normal G6PD individuals. CONCLUSIONS: This study provided detailed genotypes of G6PD deficiency in Guangdong, and would be valuable for diagnosis and research of G6PD deficiency in this area.

Determination of Total Flavonoids Contents and Antioxidant Activity of Ginkgo biloba Leaf by Near-Infrared Reflectance Method.

BACKGROUND: Total flavonoids content (TFC) is one of the most important quality indexes of Ginkgo biloba leaf, and it is concerned with total antioxidant activity. Near-infrared spectroscopy (NIR) method has showed its advantages in fast, accurate, qualitative, and quantitative analysis of various components in many quality control researches. In this study, a calibration model was built by partial least squares regression (PLSR) coupling with NIR spectrum to quantitatively analyze the TFC and total antioxidant activity of Ginkgo biloba leaf. RESULTS: During the model establishing, some spectrum pretreatment and outlier diagnosis methods were optimized to establish the final model. The coefficients of determination (R2 ) for TFC and total antioxidant activity prediction were 0.8863 and 0.8486, respectively; and the root mean square errors of prediction (RMSEP) were 2.203 mg/g and 0.2211 mM/g, respectively. CONCLUSION: These results showed that NIR method combined with chemometrics is suitable for quantitative analysis of main components and their activities and might be applied to quality control of relevant products.

[Anti-lung cancer mechanisms of diterpenoid tanshinone via endoplasmic reticulum stress-mediated apoptosis signal pathway].

At present, lung cancer ranks second and first respectively in the incidence and the mortality among malignant tumors. It is urgent to find new effective anti-lung cancer drugs with less side effects and relatively defined mechanisms. Endoplasmic reticulum stress (ERS)-mediated apoptosis pathway is an effective way to promote tumor cell apoptosis; diterpenoid tanshinone (DT), an effective part separated from Salviae Miltiorrhizae Radix et Rhizoma, was found to have an anti-lung cancer effect in previous studies via ERS-induced PERK-EIF2α pathway. In this paper, human lung adenocarcinoma PC9 cell line and nude mouse transplantation tumor model were applied to verify the anti-lung cancer effect of DT in vivo and in vitro, and illuminate the potential mechanism via ERS induced IRE1α/caspase 12 apoptosis pathway. The results showed that in vivo, DT could promote PC9 cell apoptosis in a concentration-dependent manner, up-regulate Bip, IRE1 and TRAF2 protein expressions in tumor tissue, reduce tumor weight and alleviate bodyweight loss. In vitro, DT inhibited the proliferation of PC9 cell line in a concentration-dependent manner, and destroyed the structure of mitochondria in PC9 cell, promoted Bax, IRE1α, Bip, TRAF2 and caspase 12 protein expressions, lower Bcl-2 protein expression in a time-dependent manner. DT shows a good effect on anti-lung cancer both in vivo and in vitro. The mechanism is related to the activation of ERS-induced IRE1α/caspase 12 apoptosis pathway and the promotion of cell apoptosis. ERS-mediated apoptosis pathway may be an important target of DT on anti-lung cancer.

[Space-Time Estimations and Mapping of PM2.5 Fine Particulates Based on Multi-source Data].

PM2.5 pollution in China has become an extreme environmental and social problem and has generated widespread public concern. We estimate ground-level PM2.5 from satellite-derived aerosol optical depth (AOD), topography data, meteorological data, and pollutant emissions using a new technique, Bayesian maximum entropy (BME) combined with geographically weighted regression (GWR), to evaluate the spatial and temporal characteristics of PM2.5 exposure in an eastern region of China in winter. The overall 10-fold cross-validation R2 is 0.92, and the root mean squared prediction error (RMSE) is 8.32 µg·m-3. The mean prediction error (MPE) of the predicted monthly PM2.5 is -0.042 µg·m-3, the mean absolute prediction error (MAE) is 4.60 µg·m-3. Compared with the results of the Geographically Weighted Regression model-GWR (R2=0.71, RMSE=15.68 µg·m-3, MPE=-0.095 µg·m-3, MAE=11.14 µg·m-3), the prediction by the BME were greatly improved. In this location, the high PM2.5concentration area is mainly concentrated in North China, the Yangtze River Delta, and Sichuan Basin. The low concentration area is mainly concentrated in the south of China, including the Pearl River Delta and southwest of Yunnan. Temporally, there is migration trend from the coastal areas inland, and PM2.5 pollution is most serious in December 2015 and January 2016. It is relatively low in November 2015 and February 2016.

Effects of Linderae radix extracts on a rat model of alcoholic liver injury.

Traditional treatments have a poor effect on alcoholic liver diseases. Linderae radix (LR), the dried root of Lindera aggregata (Sims) Kosterm., has been frequently used in traditional Chinese medicine for treating various diseases, and has been shown to exhibit a protective effect on liver injury. In the present study, LR extracts were made using various solvents, and then administrated to rats to establish a model of ethanol-induced liver injury. The study aimed to investigate the therapeutic effects and potential mechanism of LR extracts on acute alcoholic liver injury. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycercide (TG), cholesterol (TC), methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD) were determined using an automatic biochemistry analyzer. In addition, pathological examination was performed by hematoxylin-eosin staining. The levels of MDA and SOD, and the expression levels of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in liver tissue were investigated immunohistochemically. The expression of cytochrome P450 2E1 (CYP2E1) mRNA was quantified by reverse transcription-quantitative polymerase chain reaction. The results indicated that LR extracts improved the histopathological status and decreased the serum levels of ALT, AST, TG, TC and MDA. Furthermore, the levels of MDA and inflammatory mediators (NF-κB, TNF-α and IL-1ß) were decreased in liver tissues, and the overexpression of CYP2E1 mRNA induced by ethanol treatment. LR extracts exhibited a protective effect on alcoholic liver injury and the mechanism may be associated with the anti-inflammatory and anti-oxidative action.

[Effects of lotus leaf on inflammatory factors and liver AdipoR2 expressions in rats with NAFLD induced by high fat diet and high glucose].

Lotus leaf (LL) is one of the traditional Chinese herbs which can be used for both pharmaceutical and food application, and it posses lipid regulating efficacy. To observe the effect of LL on experimental nonalcoholic fatty liver disease (NAFLD) and its potential mechanism, a NAFLD model was established by feeding SD rat with high-fat and high-glucose diet. LL was administrated to rats in experiment group at the same time. AST,ALT,Cr,BUN,GLU levels in serum were determined by automatic biochemical analyser and TNF-α,IL-6,INS,ADPN,LEP and liver NF-κB,TGF-ß1 levels were determined by ELISA according to the specification of the kits. HE staining was applied for histopathological examination and RT-PCR,Western blot was applied for AdipoR2 mRNA and protein expression．Results have shown that LL could significantly decrease ALT,AST,IL-6 level in serum and NF-κB,TGF-ß1 level in liver,promote adiponectin content in serum and AdipoR2 protein expression in liver and could alleviate hepatocyte lipid degeneration. These results indicating that LL has protective effect for NAFLD induced by high-fat and high-glucose diet via promoting AdipoR2 expression, improving insulin resistance and inhibiting inflammatory reaction.

Optimal technique of three-dimensional MRI of the lumbar nerve root and its radicular vein in normal and lumbar disc herniation patients.

BACKGROUND: Although three-dimensional MRI (3D-MRI) of short T1 inversion recovery turbo spin-echo (STIR TSE) has showed superior to two-dimensional MRI (2D-MRI) in showing the spinal cord and lumbar nerve roots, it remains difficult in demonstrating radicular vein at present. We have found that short T1 inversion recovery long time echo (STIR LONG TE) was better in showing radicular vein. To further study the methods and character of the 3D-MRI of lumbar nerve root, ganglions and radicular vein in normal and lumbar disc herniation (LDH) adults, in the present study, we evaluated two 3D-MRI techniques, STIR TSE and STIR LONG TE for demonstrating lumbar nerve roots and especial radicular vein in normal and LDH adults. METHODS: Twelve normal adult persons and 19 LDH patients were included in this study; special oblique coronal location was adopted. STIR TSE and STIR LONG TE were performed in all participants, and the detection rates of radicular vein and nerve root of L3, L4, L5, S1 were calculated. The grading system was used in grading compromise of the intraspinal extradural lumbar nerve root, ganglion and radicular vein in LDH patients, and all the grading injury of nerve root, ganglion and radicular vein had been evaluated. RESULTS: The definite rate of radicular vein (DRRV) of 3D-MRI of STIR LONG TE was significantly different from that of STIR TSE. DRRV of STIR LONG TE was L3, 91.7%, L4, 100%, L5, 100%, S1, 100% and that of STIR TSE was L3, 33.3%, L4, 37.5%, L5, 58.3%, S1, 45.8% in normal adults. It showed no difference between STIR LONG TE and STIR TSE in the detection rate of nerve root. The different patho-injuries of nerve root, ganglion and radicular vein could be seen in all LDH patients by the 3D-MRI of STIR LONG TE. The mean score of Japanese Orthopaedic Association (JOA) was 16.16, and 29 nerve roots were calculated in all the study. The mean grading injury of nerve root was 2.17, that of nerve root ganglion was 1.28, that of radicular vein was 1.83, and the mean co-grading injury of nerve root, ganglion and radicular vein was 5.31. The correlation coefficient was 0.478 (P = 0.010) between the score of JOA and that of radicular vein. CONCLUSION: The 3D-MRI of STIR LONG TE is superior to STIR TSE for not only detecting the lumbar nerve root, ganglion and especial radicular vein in normal adults, but also displaying their patho-injuries degree in LDH patients.