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Background and Purpose Squalene epoxidase (SQLE) is a key enzyme involved in cholesterol biosynthesis, but increasing evidence reveals that SQLE is abnormally expressed in some types of malignant tumors, and the underlying mechanism remains poorly understood. Experimental Approach Bioinformatics analysis and RNA sequencing were applied to detect to differentially expressed genes in clinical HCC tumors. AnnexinV-FITC/PI, EdU assay, transwell, IHC staining, cytoskeleton F-actin filaments assay, RNA sequencing, dual-luciferase reporters and HE staining were evaluated to investigate the pharmacological effects and possible mechanisms of SQLE. Key Results We found that SQLE expression is specifically elevated in HCC tumors, correlating with poor clinical outcomes. SQLE promoted HCC growth, EMT, and metastasis both in vitro and in vivo. In contrast, silencing of SQLE expression prevented HCC development. Both RNA-seq and functional experiments revealed that the protumorigenic effect of SQLE on HCC is closely related to the activation of cellular TGF-β/SMAD signaling, but interestingly, the stimulatory effect of SQLE on TGF-β/SMAD signaling and HCC development is also critically dependent on STRAP, a serine and threonine kinase. SQLE expression is well correlated with STRAP in HCC, and further, to amplify TGF-β/SMAD signaling, SQLE even transcriptionally increased STRAP gene expression mediated by the trans-acting factor AP-2α. Finally, as a chemical inhibitor of SQLE, NB-598 markedly inhibited HCC cell growth and tumor development in mouse models. Conclusions and Implications Taken together, SQLE serves as an oncogene in HCC development by activating TGF-β/SMAD signaling, and targeting SQLE could be useful in drug development and therapy for HCC.

Bone defects remain a challenging problem for doctors and patients in clinical practice. Processed pyritum is a traditional Chinese medicine that is often used to clinically treat bone fractures. It contains mainly Fe, Zn, Cu, Mn, and other elements. In this study, we added the extract of processed pyritum to β-tricalcium phosphate and produced a porous composite TPP (TCP/processed pyritum) scaffold using digital light processing (DLP) 3D printing technology. Scanning electron microscopy (SEM) analysis revealed that TPP scaffolds contained interconnected pore structures. When compared with TCP scaffolds (1.35 ± 0.15 MPa), TPP scaffolds (5.50 ± 0.24 MPa) have stronger mechanical strength and can effectively induce osteoblast proliferation, differentiation, and mineralization in vitro. Meanwhile, the in vivo study showed that the TPP scaffold had better osteogenic capacity than the TCP scaffold. Furthermore, the TPP scaffold had good biosafety after implantation. In summary, the TPP scaffold is a promising biomaterial for the clinical treatment of bone defects.

Significance The two-dimensional (2D) magnetic semiconductor CrI3 hosts a variety of strong and tunable magneto-optical effects and allows for the development of novel magneto-optical devices. While the elastic magneto-optical effects in CrI3 are well understood, its recently discovered inelastic magneto-Raman effect remains to have case-specific interpretations varying upon the thickness of CrI3. We perform comprehensive Raman measurements on 2D CrI3 with polarization, temperature, layer number, and magnetic field dependence. We resolve a Davydov-split–induced N-fold multiplet in N-layer CrI3 and reveal the distinct magneto-Raman behaviors of individual phonons within the multiplet. Our results discover a layered-magnetism–coupled phonon scattering mechanism that explains the rich magneto-Raman effect in CrI3 of arbitrary thickness and elucidates the spin–phonon coupling physics in layered magnets., We used a combination of polarized Raman spectroscopy experiment and model magnetism–phonon coupling calculations to study the rich magneto-Raman effect in the two-dimensional (2D) magnet CrI3. We reveal a layered-magnetism–assisted phonon scattering mechanism below the magnetic onset temperature, whose Raman excitation breaks time-reversal symmetry, has an antisymmetric Raman tensor, and follows the magnetic phase transitions across critical magnetic fields, on top of the presence of the conventional phonon scattering with symmetric Raman tensors in N-layer CrI3. We resolve in data and by calculations that the first-order Ag phonon of the monolayer splits into an N-fold multiplet in N-layer CrI3 due to the interlayer coupling (N≥2) and that the phonons within the multiplet show distinct magnetic field dependence because of their different layered-magnetism–phonon coupling. We further find that such a layered-magnetism–phonon coupled Raman scattering mechanism extends beyond first-order to higher-order multiphonon scattering processes. Our results on the magneto-Raman effect of the first-order phonons in the multiplet and the higher-order multiphonons in N-layer CrI3 demonstrate the rich and strong behavior of emergent magneto-optical effects in 2D magnets and underline the unique opportunities of spin–phonon physics in van der Waals layered magnets.

Blood stasis syndrome (BSS) is characterized by blood retardation and is the major cause of some deadly diseases. Some factors that affect BSS have been identified. However, the small molecule that related to BSS is still largely unknown. Traditional Chinese Medicine (TCM), such as Sanleng and Ezhu, has been used for a long time in treating BSS and promising outcomes have been achieved. However, the mechanism of how they work is unclear. Thus, we constructed the Rat BSS model and treated them with Sanleng and Ezhu. Then, the liver dialysis of those rats was collected and the small molecule metabolites were analyzed by GC-MS based metabolomics approach. Our results showed after Sanleng and Ezhu treatment, several small molecule metabolites were significantly changed metabolites (VIP1 and P0.05). Pathway enrichment analysis also showed that Sanleng and Ezhu share the similar mechanism in treating BSS, such as regulating Glyoxylate and dicarboxylate metabolism pathway and energy metabolism. Besides, we also identified some key metabolites that were significantly correlated with BSS. In conclusion, those findings uncover the mechanism of Sanleng and Ezhu in treating BSS.

Crataegi Fructus (CF) is widely used as a medicinal and edible material around the world. Currently, different types of processed CF products are commonly found in the market. Quality evaluation of them mainly relies on chemical content determination, which is time and money consuming. To rapidly and nondestructively discriminate different types of processed CF products, an electronic nose coupled with chemometrics was developed. The odour detection method of CF was first established by single-factor investigation. Then, the sensor array was optimised by a stepwise discriminant analysis (SDA) and analysis of variance (ANOVA). Based on the best-optimised sensor array, the digital and mode standard were established, realizing the odour quality control of samples. Meanwhile, mathematical prediction models including the discriminant formula and back-propagation neural network (BPNN) model exhibited good evaluation with a high accuracy rate. These results suggest that the developed electronic nose system could be an alternative way for evaluating the odour of different types of processed CF products.

We use a combination of polarized Raman spectroscopy experiment and model magnetism-phonon coupling calculations to study the rich magneto-Raman effect in the two-dimensional (2D) magnet $\mathrm{CrI_3}$. We reveal a novel layered-magnetism-assisted phonon scattering mechanism below the magnetic onset temperature, whose Raman excitation breaks time-reversal symmetry, has an antisymmetric Raman tensor, and follows the magnetic phase transitions across critical magnetic fields, on top of the presence of the conventional phonon scattering with symmetric Raman tensors in $N$-layer $\mathrm{CrI_3}$. We resolve in data and by calculations that the 1st-order $A_g$ phonon of monolayer splits into a $N$-fold multiplet in $N$-layer $\mathrm{CrI_3}$ due to the interlayer coupling ($N$>=2) and that the phonons with the multiple show distinct magnetic field dependence because of their different layered-magnetism-phonon coupling. We further find that such a layered-magnetism-phonon coupled Raman scattering mechanism extends beyond 1st-order to higher-order multi-phonon scattering processes. Our results on magneto-Raman effect of the 1st-order phonons in the multiplet and the higher-order multi-phonons in $N$-layer $\mathrm{CrI_3}$ demonstrate the rich and strong behavior of emergent magneto-optical effects in 2D magnets and underlines the unique opportunities of new spin-phonon physics in van der Waals layered magnets., 16 pages, 4 figures + supplementary material

With the development of the Chinese transportation industry, the number of bridges has increased significantly, but this results in high pressure of structural maintenance and management. Bridge management system (BMS) is critical for efficient maintenance and ensured safety of bridge structures during long-term operation. Building information modeling (BIM) is an emerging technology with powerful visualization and informatization capability, making it an ideal tool for developing modern management systems. This paper introduces the development of a bridge management system based on the BIM technology. Industry Foundation Classes (IFC) and International Framework for Dictionaries (IFD) standards are studied and extended, and coding rules are proposed for the Chinese bridge industry. Also, a standard structural modeling method is proposed to fast build the bridge BIM model. Web-BIM oriented bridge management is proposed, and portable devices are introduced into the system. Collaborative management is realized for different users. The BIM-based maintenance management system is designed. Finally, a practical BIM-based BMS is established for a long-span cable-stayed bridge in China. This system integrates the BIM with the geographic information system (GIS) and contains information management, inspection management, technical condition evaluation, and enables users to cooperate with each other. Such a BMS could help to improve the management efficiency and ensure its normal operation, providing a useful platform for the maintenance of massive bridges in China.

Yi Huang decoction (YHD) has been used as one of famous traditional formula because of its unique effectiveness against gynecological diseases. YHD is composed of five herbs, including the rootstock of Dioscoma opposita Thunb. (Dioscoreaceae), the kernel of Etayale ferx Salisb. (Nymphaeaceae), the bark of Phellodendron chinense Schneid. (Rutaceae), the seed of Plantago asiatica L. (Plantaginaceae), and the seed of Ginkgo biloba L. (Ginkgoaceae). To effectively control the quality, the processing method for YHD was optimized by means of single factor test as well as orthogonal test in this study. A completely validated method based on HPLC coupled with diode array detector was performed on a Kromasil C(18) column at 30° with mobile phase of 0.1% aqueous phosphoric acid and acetonitrile. As a result, HPLC fingerprint on the basis of the chromatographic data from 32 batches of samples was obtained, which contained 44 common peaks. Among these common peaks, 6 peaks were identified as geniposidic acid, berberine hydrochloride, palmatine hydrochloride, phellodendrine chloride, magnoflorine, and verbascoside, respectively, based on their retention time relative to the standards. Meanwhile, the contents of these 6 compounds were also simultaneously examined. In sum, this study offered valuable information for the proper processing and quality control for YHD.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively triggers cancer cell death via its association with death receptors on the cell membrane, but exerts negligible side effects on normal cells. However, some non-small-cell lung carcinoma (NSCLC) patients exhibited resistance to TRAIL treatment in clinical trials, and the mechanism varies. In this study, we described for the first time that toosendanin (TSN), a triterpenoid derivative used in Chinese medicine for pain management, could significantly sensitize human primary NSCLC cells or NSCLC cell lines to TRAIL-mediated apoptosis both in vitro and in vivo, while showing low toxicity against human primary cells or tissues. The underlying apoptotic mechanisms involved upregulation of death receptor 5 (DR5) and CCAAT/enhancer binding protein homologous protein, which is related to the endoplasmic reticulum stress response, and is further associated with reactive oxygen species generation and Ca2+ accumulation. Surprisingly, TSN also induced autophagy in NSCLC cells, which recruited membrane DR5, and subsequently antagonized the apoptosis-sensitizing effect of TSN. Taken together, TSN can be used to sensitize tumors and the combination of TRAIL and TSN may represent a useful strategy for NSCLC therapy; moreover, autophagy serves as an important drug resistance mechanism for TSN.

Gardeniae Fructus (G.Fructus), the fruit of Gardenia jasminoides Ellis (Rubiaceae), is a commonly used traditional Chinese medicine (TCM) that has been used for the treatment of hepatitis, jaundice, hypersonic, diabetes and hematuria. Numerous researches have demonstrated that the major active constituents in G.Fructus were responsible for the majority of medical effects of this fruit and their quantification were important for the quality control of G.Fructus. However, in the current quality control standard, only geniposide was used as characteristic marker of G.Fructus, which could not reflect the overall quality of this fruit. In order to identify more chemical makers for improving the quality control standard and evaluate producing areas differentiation of G.Fructus, in the present study, a novel and sensitive high-performance liquid chromatography-diode array detector coupled to an electrospray tandem mass spectrometer (HPLC-DAD-ESI/MS) was developed for the simultaneous determination of 8 major constituents, including geniposidic acid (1), chlorogenic acid (2), genipin-1-β-gentiobioside (3), geniposide (4), genipin (5), rutin (6), crocin-1 (7), crocin-2 (8) in G.Fructus. Moreover, chemometric analysis techniques with principal component constituent analysis (PCA) and cluster analysis (CA) involved were introduced in statistical analysis of 8 investigated constituents in the 34 batches samples to discriminate the samples from different producing areas. The results indicated that the contents of the 8 major bioactive constituents in G.Fructus varied significantly among different producing areas. From results of the loading plot from PCA analysis, genipin-1-β-gentiobioside may have more influence in discriminating the sample from different producing areas, and which was found to be the most abundant bioactive component besides geniposide in all the 34 batches samples, suggesting that it should be added as chemical marker for further investigation on the pharmacological actions and the quality control of G.Fructus.

Summary The ripe fruits of Schisandrae chinensis have a long history of use in traditional Chinese medicine to treat diseases and improve health. There is substantial evidence that lignan constituents are mainly responsible for the beneficial effects of this plant medicine. The amounts of the major bioactive lignans in this plant vary widely with species, habitat, and the collecting time, and as such, establishment of an HPLC fingerprint for quality control of this herbal medicine is of particular importance. To achieve this, ten batches of Fructus schisandrae chinensis were collected from Tieli, in China, and their chemical components were analyzed under optimized HPLC conditions. On the basis of the chromatographic data, a consistent HPLC fingerprint pattern containing 20 common peaks was obtained. Among these common peaks, six were identified as schizandrin, schizandrol B, schisantherin, deoxyschiandrin, γ-schizandrin B, and schizandrin C. On the basis of this HPLC fingerprint and principal-components ...

To study the cytotoxicity of four alkaloids: brucine, strychnine, brucine N-oxide and isostrychnine from nux vomica on SMMC 7721 cells and their possible mechanisms, MET assay was used to examine the growth inhibitory effects of these alkaloids. Brucine revealed the strongest growth inhibitory effect on SMMC-7721 cells. Furthermore, as directly observed under an inverted microscope, fluorescent microscope and transmission electronic microscope, brucine caused SMMC-7721 cell shrinkage, membrane blobbing, formation of apoptotic body as well as nucleus condensation, all of which are typical characteristics of apoptotic programmed cell death. In addition, brucine dose-dependently caused SMMC-7721 cells apoptosis via formation of subdipolid DNA and phosphatidylserine externalization, as evidenced by flow cytometry analysis. The brucine-induced apoptosis was partially attributed to the activation of caspase 3 as well as cyclooxygenase 2 inhibition, since neither caspase 3 specific inhibitor, z-DEVD-fmk nor was exogenous addition of prostaglandin E(2) able to completely abrogate the brucine-induced SMMC 7721 cell apoptosis. In sum, this paper indicate that the major alkaloids present in the seed of Strychnos nux-vomica are effective against SMMC-7721 cells proliferation, among which brucine proceeds SMMC-7721 cells death via apoptosis, probably through the participation of caspase 3 and cyclooxygenase 2.

In an attempt to dissect the mechanism of Strychnos nux-vomica, a commonly used Chinese folk medicine in the therapy of liver cancer, the cytotoxic effects of four alkaloids in Strychnos nux-vomica, brucine, brucine N-oxide, strychnine, and isostrychnine, on human hepatoma cells (HepG2) were screened by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrasolium bromide (MTT) assay. Brucine, among the four alkaloids, exhibited the strongest toxic effect, the mechanism of which was found to cause HepG2 cell apoptosis, since brucine caused HepG2 cell shrinkage, the formation of apoptotic bodies, DNA fragmentation, cell cycle arrest, as well as phosphatidylserine externalization, all of which are typical characteristics of apoptotic programmed cell death. Brucine-induced HepG2 cell apoptosis was caspase dependent, with caspase-3 activated by caspase-9. Brucine also caused the proteolytic processing of caspase-9. In addition, brucine caused depolarization of the mitochondrial membrane of HepG2 cells, the inhibition of which by cyclosporine A completely abrogated the activation of casapses and release of cytochrome c in brucine-treated HepG2 cells. These findings suggested a pivotal role of mitochondrial membrane depolarization in HepG2 cell apoptosis elicited by brucine. Furthermore, brucine induced a rapid and sustained elevation of intracellular [Ca2+], which compromised the mitochondrial membrane potential and triggered the process of HepG2 cell apoptosis. Finally, Bcl-2 was found to predominately control the whole event of cell apoptosis induced by brucine. The elevation of [Ca2+]i caused by brucine was also suppressed by overexpression of Bcl-2 protein in HepG2 cells. From the facts given above, Ca2+ and Bcl-2 mediated mitochondrial pathway were found to be involved in brucine-induced HepG2 cell apoptosis.

The ripe fruits of Gardenia jasminoides Ellis have been used as traditional Chinese medicine to treat diseases for a long history. Lines of evidence demonstrate that multiple active constituents are responsible for the therapeutic effects of this herbal medicine. However, effective methods for quality control of this herbal medicine are still lacking. In this study, a high-performance liquid chromatography (HPLC) fingerprint analysis was performed on a SinoChrom ODS-BP C18 column (4.6 mm × 250 mm, 5 μm) at 30°C with mobile phase of aqueous solution with 0.1% formic acid and acetonitrile. On the basis of the chromatographic data from 32 batches samples, the HPLC fingerprint pattern containing 27 common peaks was obtained. Among these common peaks, seven peaks were identified by the electrospray ionization-mass spectrometry as geniposidic acid, genipin-1-β-gentiobioside, chlorogenic acid, geniposide, rutin, crocin-1 and crocin-2 and the contents of these seven compounds were simultaneously determined. Finally, chemometric methods including hierarchical clustering analysis and principal component analysis were successfully applied to differentiate the samples from six producing regions. In sum, the data, as described in this study, offer valuable information for the quality control and proper use of Gardeniae Fructus.

A new chemical component, cis-Z,Z'-3a.7a',7a.3a'-dihydroxyligustilide, was isolated from Angelica sinensis and its structure elucidated from its NMR and MS spectra and confirmed by X-ray single crystal diffraction analysis. We also explored the antioxidative properties of cis-Z,Z'-3a.7a',7a.3a'-dihydroxyligustilide on human umbilical vein endothelial cells (HUVECs) against injuries induced by hydrogen peroxide (H(2)O(2)) using an MTT assay and flow cytometry analysis. In addition, the activities of superoxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH), nitric oxide (NO) and reactive oxygen species (ROS) were determined. We found that cis-Z,Z'-3a.7a',7a.3a'-dihydroxyligustilide increased the viability of HUVECs injured by H(2)O(2) in a dose-dependent manner, reduced the apoptosis of HUVEC, and enhanced HUVEC proliferation. Our results demonstrated the remarkable in vitro antioxidative activities of this compound, indicating that it could be a potential antioxidant with protective effects against H(2)O(2)-induced HUVEC injuries.

Psoralea Fructus, the dried and ripe fruit of Psoralea corylifolia L., have been used as traditional medicine. There is substantial evidence that multiple constituents are responsible for the beneficial effects of this medicine. To effectively control the quality of this herbal medicine, HPLC fingerprint analysis was performed on a SinoChrom ODS-BP column with mobile phase of a gradient prepared from H2O and CH3CN, which the conditions used for gradient elution were: 0-10 min, 5-45% CH3CN; 10-45 min, 45-70% CH3CN; 45-50 min, 70-100% CH3CN; 50-60 min, 100-100% CH3CN, and the flow rate was 1.0 ml/min. It was obtained on the basis of the chromatographic data from 28 batches of samples, which contained 26 common peaks and 13 peaks were identified by the electrospray ionization-mass spectrometry as psoralen, isopsoralen, isobavachin, neobavaisoflavone, bavachin, corylin, broussochalcone B, psoralidin, isobavachalcone, bavachinin, corylifol A, bavachalcone and backuchiol. The contents of these 13 compounds were also simultaneously examined. By using principal component analysis, 28 batches of samples collected from 6 producing locations with different collecting time were evaluated and differentiated. In summary, the data as described in this study offer valuable information for quality control and proper use of Psoralea Fructus.