Two new saponins from the rhizomes of Paris yunnanensis Franch.

The phytochemical investigation on the rhizomes of Paris yunnanensis Franch. resulted in the discovery and characterisation of six compounds, including two new saponins named parisyunnanosides M-N (1-2), and four known ones (3-6). The structures of isolated compounds were determined by spectroscopic data analysis and chemical methods. Compound 2 is a pregnane-type saponin with a special α,ß-unsaturated carboxylic acid moiety at C-17, which is first discovered in genus Paris. The anti-inflammatory activity of the isolated compounds was assessed in vitro. The results demonstrated that compounds 3 and 4 could significantly inhibit the production of NO which was induced by LPS in RAW 264.7 cells with IC50 values of 0.67 ± 0.17 µM and 0.85 ± 0.12 µM, respectively.

Two previously undescribed cholestanol saponins from the rhizomes of Paris fargesii var. petiolata.

Two previously undescribed cholestanol saponins, parpetiosides F - G (1-2), and six known analogs (3-8) were isolated from the rhizomes of Paris fargesii var. petiolata. Their structures were elucidated by extensive spectroscopic data analysis and chemical methods. Compound 1 was a rare 6/6/6/5/5 fused-rings cholestanol saponin with disaccharide moiety linked at C-26 of aglycone which was hardly seen in genus Paris. All of these compounds were discovered in this plant for the first time. In addition, the cytotoxicities of saponins (1-8) against three human cancer cell lines (U87, HepG2 and SGC-7901) were evaluated by CCK-8 method, and saponins 5-8 displayed certain cytotoxicities. The strong interactions between saponins 5-8 and SCUBE3, an oncogene for glioma cells, were displayed by molecular docking.

Thermally reversible hydrogels printing of customizable bio-channels with curvature.

Replicating intricate bio-channels, akin to expansive vascular networks, offers numerous advantages including self-repair, replacing damaged bio-channels, testing drugs, and biomedical devices. But, crafting multi-sized, editable bio-channels with specific curvatures, particularly using natural polymer-based bio-inks, poses a significant challenge. To address this, this study introduces a temperature-driven indirect printing method, exemplified by the diploic vein. Here, K-carrageenan (kca)-silk fiber (SF)-hyaluronic acid (HA)/hFOB 1.19 (SV40 transfection of human osteoblasts) and kca-collagen-HA/HUVECs (human umbilical vein endothelial cells) are employed to fabricate vascular-like walls and lumens, utilizing their thermoreversible properties to create multi-stage bifurcated lumens. Precise spatial curvature was generated by heating the vascular network wrapped in poly(N-isopropyl acrylamide) (PNIPAAm)-poly(ethylene glycol) diacrylate (PEGDA). Since temperature is specific to the thermal material carrying the cells, the rheological properties of bioinks, modeling temperature parameters, and their impact on printing size was explored. Additionally, mechanical properties and curvature response were characterized to determine the necessary process parameters for achieving the desired size. Ultimately, in vitro bioprinting experiments involving HUVECs and hFOB 1.19 demonstrate cell viability, adhesion, proliferation, and migration within the intraluminal hydrogel scaffold. This approach allows for customizing bio-channel content and controlling curvature programming, providing new prospects for in vitro biochannel production, with potential benefits for pathology research.

Steroid and triterpenoid saponins from the rhizomes of Paris polyphylla var. stenophylla.

Five new saponins, including three steroid saponins, paristenoids A-C (1-3), and two triterpenoid saponins, paristenoids D-E (4-5), along with four known ones (6-9) were isolated from the rhizomes of Paris polyphylla var. stenophylla. The structures of the isolated compounds were identified mainly by detailed spectroscopic analysis, including extensive 1D and 2D NMR, MS, as well as chemical methods. Compound 3 is a new cyclocholestanol-type steroidal saponin with a rare 6/6/6/5/5 fused-rings cholestanol skeleton, and this skeleton has been first found from the genus Paris. The cytotoxicities of the isolated compounds against three human three glioma cell lines (U87MG, U251MG and SHG44) were evaluated, and compound 7 displayed certain inhibitory effect with IC50 values of 15.22 ± 1.73, 18.87 ± 1.81 and 17.64 ± 1.69 µmol·L-1, respectively.

The effect of natural and socioeconomic factors on haze pollution from global and local perspectives in China.

Analyzing the factors that cause haze and the regional differences in the influence of factors on haze is the premise and critical to precise prevention and control of haze pollution. This paper explores the global effects of haze pollution drivers and the spatial heterogeneity of factors on haze pollution using global and local regression models. The results show that, from a global perspective, a 1 µg/m3 increase in the average PM2.5 concentration of a city's neighbors will increase the city's PM2.5 concentration by 0.965 µg/m3. Temperature, atmospheric pressure, population density, and green coverage of built-up areas are positively associated with haze, while GDP per capita is the opposite. From a local perspective, each factor has different influencing scales on haze pollution. Specifically, technical support is on a global scale, and for every 1 unit increase in technical support level, the PM2.5 concentration will decrease by 0.106-0.102 µg/m3. The influencing scales of other drivers are local. In southern China, the concentration of PM2.5 decreases by 0.001-0.075 µg/m3 for every 1 °C increase in temperature, while in northern China, the concentration of PM2.5 increases by 0.001-0.889 µg/m3. In the region around the Bohai Sea in eastern China, the concentration of PM2.5 will decrease by 0.001-0.889 µg/m3 for every 1 m/s increase in wind speed. Population density positively impacts haze pollution, and the impact intensity gradually increases from 0.097 to 1.140 from south to north. For every 1% increase in the proportion of the secondary industry in southwest China, the PM2.5 concentration will increase by 0.001-0.284 µg/m3. For cities in northeast China, for every 1% increase in the urbanization rate, the PM2.5 concentration will decrease by 0.001-0.203 µg/m3. These findings help policymakers develop targeted joint prevention and control policies for haze pollution, considering regional differences.

Impact of anti-dumping on global embodied air emissions: a complex network perspective.

After the rise of trade protectionism, anti-dumping has become a common means of political and trade games between countries. Global supply chains move production emissions between countries or regions through trade. In the context of carbon neutrality, anti-dumping measures representing the right to trade may become a tool for the game of emission rights between countries. Therefore, it is very important to study the environmental effects of anti-dumping to cope with global climate change and promote national development. Taking a sample of 189 countries and regions from the EORA input-output table with a study period of 2000-2016, we use the complex network, multi-regional input-output and panel regression models to verify the impact of anti-dumping on air emission transfer by constructing an anti-dumping network and an embodied air emission network. The results show that the initiator of anti-dumping can use anti-dumping to realize the cross-border transfer of ecological costs, reduce the burden of emission reduction and save more on emission quota. Developing countries lacking the right to speak in trade will increase the export volume of commodities after being subjected to a large number of anti-dumping sanctions, thus paying higher ecological costs and consuming more emission quotas. From a global perspective, additional emissions from product production can further contribute to global climate change.

Risk Transmission of Trade Price Fluctuations from a Nickel Chain Perspective: Based on Systematic Risk Entropy and Granger Causality Networks.

Nickel is a strategic mineral resource, with 65% of nickel being used in stainless steel. The situation in Ukraine starting in February 2022 has led to significant fluctuations in nickel prices, with prices of nickel products along the same chain affecting and passing through each other. Using systematic risk entropy and granger causality networks, we measure the volatility risk of trade prices of nickel products using the nickel industry chain trade data from 2000-2019 and explore the transmission patterns of different volatility risk prices from the industry chain perspective. The findings show that: (1) Nickel ore has the highest risk of import trade price volatility and a strong influence, but low risk transmission. Stainless steel has the highest trade price impact but is also subject to the strongest passive influence. (2) The Americas have a higher risk of trade price volatility but a weaker influence. The influence and sensitivity of trade prices is stronger in Asia and Europe. (3) Indonesia's stainless steel export prices have a high rate of transmission and strong influence. Germany's ferronickel export prices are highly susceptible to external influences and can continue to spread loudly. Russian nickel ore export prices are able to quickly spread their impact to other regions.

Design and Optimization of a New Anti-reflux Biliary Stent With Retractable Bionic Valve Based on Fluid-Structure Interaction Analysis.

Duodenal biliary reflux has been a challenging common problem which could cause dreadful complications after biliary stent implantation. A novel anti-reflux biliary stent with a retractable bionic valve was proposed according to the concertina motion characteristics of annelids. A 2D equivalent fluid-structure interaction (FSI) model based on the axial section was established to analyze and evaluate the mechanical performances of the anti-reflux biliary stent. Based on this model, four key parameters (initial shear modulus of material, thickness, pitch, and width) were selected to investigate the influence of design parameters on anti-reflux performance via an orthogonal design to optimize the stent. The results of FSI analysis showed that the retrograde closure ratio of the retractable valve primarily depended on initial shear modulus of material (p < 0.05) but not mainly depended on the thickness, pitch, and width of the valve (p > 0.05). The optimal structure of the valve was finally proposed with a high retrograde closing ratio of 95.89%. The finite element model revealed that the optimized anti-reflux stent possessed improved radial mechanical performance and nearly equal flexibility compared with the ordinary stent without a valve. Both the FSI model and experimental measurement indicated that the newly designed stent had superior anti-reflux performance, effectively preventing the duodenobiliary reflux while enabling the bile to pass smoothly. In addition, the developed 2D equivalent FSI model provides tremendous significance for resolving the fluid-structure coupled problem of evolution solid with large deformation and markedly shortens the calculation time.

Adjusting the accuracy of PEGDA-GelMA vascular network by dark pigments via digital light processing printing.

Vascularization is one of the most important factors greatly influencing scaffold regeneration. In this study, a precise network of hollow vessels was printed by digital light processing (DLP) with poly(ethylene glycol) diacrylate (PEGDA)/gelatin-methacryloyl (GelMA), and dark pigmentation absorbers were added to ensure printing accuracy. First, the compound bio-inks of the PEGDA-GelMA hydrogel were prepared for direct vascular printing, and a high-precision DLP system was established. Second, the printing effects of three dark absorbers, namely, nigrosin, brilliant black, and brilliant blue, on the x-, y-, and z-axes were studied. By printing models with different densities, it was determined that 0.2% nigrosin, 0.1% brilliant black, and 0.3% brilliant blue had better effects on the x- and y-axes accuracy, and the absorbance of the absorbers played a decisive role in adjusting the accuracy. Additionally, to solve the problem of uneven curing on the upper and lower surfaces caused by the addition of an absorber with high absorbance, a model of the difference in curing width between the upper and lower surfaces of a unit-layer slice based on high-absorbance absorbers was established, and the reference value for the slice thickness was calculated. Third, the biological and mechanical properties of the bio-inks were verified with scanning electron microscopy and Fourier transform infrared, and by tensile, swelling, degradation, and cytotoxicity tests on different concentrations of PEGDA-GelMA hydrogel and absorbers. The results showed that 30% PEGDA-7% GelMA/0.1% brilliant black was the optimal preparation to print a hollow vascular network. The error of the printing tube wall and cavity was between 1% and 3%, which demonstrates the high precision of the method. Human umbilical vein endothelial cells were planted in the lumen, and the survival rate achieved 107% on the seventh day, demonstrating the good biocompatibility of the composite hydrogel.

Surface modification and effects on tribology by laser texturing in Al2O3.

We investigate the surface modification by laser texturing and effects thereof on the tribological performance in Al2O3. By detailed observation for microstructure evolution, it has been shown that there were three distinct modification morphologies by laser treatment: dense surface microfeatures, "coral" dendritic structures, and coarse grains. X-ray diffraction (XRD) results indicated that there was no formation of metastable phases due to low supercooling in solidification in the nanosecond laser regime. The formation of AlN compounds in the laser-treated region was examined by using x-ray photoelectron spectroscopy (XPS), which led to dense surface microfeatures and randomly distributed pores formation in the laser treated region. The formation of "coral" dendritic structures on the edge of groove and coarse grains in the vicinity of the laser surface was attributed to the fast-cooling rates. Wear tests were carried out to analyze the effect of laser texturing on tribological performance. The results of coefficients of friction (COF) illustrated that laser texturing can significantly improve COFs for dry friction; however, it decreases the COFs for wet friction. The mechanism of wear was explained based on a SEM measurement for worn surfaces; the formation of surface texture can store abrasive particles and debris lead to hydrodynamic lubricant film formation and the COFs significantly reducing for wet friction.

Characterization of eight unknown impurities and analysis of their source in xinfujunsu and injection by liquid chromatography coupled with ion trap/time-of-flight mass spectrometry.

Eight unknown impurities in xinfujunsu and its injection were characterized by liquid chromatography coupled with ion trap/time-of-flight mass spectrometry (LC-IT-TOF MS). In order to determine the m/z values of the molecular ions and predict the formulas of all detected impurities, full scan LC-MS in positive ion mode was firstly executed to obtain the m/z value of the molecules. Then LC-MS2, LC-MS3 and LC-MS4 were carried out on target compounds to obtain as much structural information as possible. Based on MSn spectral data and exact mass measurements, the chemical structures of eight unknown impurities were characterized, among which three impurities were degradation impurities and five impurities were process impurities. In addition, the source of impurities and the correlation between process and impurities were also studied. The production of degraded impurities was caused in the high pressure sterilization process of xinfujunsu injection. Based on characterization of impurities, this study revealed the cause of impurity production and provided guidance for enterprises to improve the process to reduce impurity content. Furthermore, this study also provided scientific basis for the further improvement of official monographs in pharmacopoeias.

Effect of surface modification on wettability and tribology by laser texturing in Al2O3.

The life of ceramic tools restricts the development of the manufacturing industry and can be increased through the enhancement of surface performance. Laser surface texturing is a feasible technology to improve ceramic tool life based on the relationship between surface properties and the laser-texturing process. In this study, ${{\rm Al}_2}{{\rm O}_3}$ substrates have been textured by an ytterbium fiber laser system with a wavelength of 1064 nm and a pulse duration of 50 ns. First, the damage threshold of ${{\rm Al}_2}{{\rm O}_3}$ was measured to provide a basis for selecting laser-texturing parameters. The surface morphology was characterized using a white confocal scanning microscope and a scanning electron microscope to investigate the characteristics of laser processing. Water contact angles were measured to investigate the relationship between laser parameters and changes in wettability. The surface energy of the superhydrophobic ceramic was calculated based on the contact angle. Combined X-ray photoelectron spectroscopy (XPS) measurement was used to explore the mechanism of wettability changes from the chemical component and microstructure perspectives. The friction coefficient of ${{\rm Al}_2}{{\rm O}_3}$ was determined by a ball-on-disc wear test. The results showed that laser texturing can significantly improve the surface hydrophobicity and friction stability.

Parameterized design and fabrication of porous bone scaffolds for the repair of cranial defects.

In bone tissue engineering, the structure of a scaffold is very important for cell growth and bone regeneration. It is better to make the scaffold resemble the native cancellous bone because natural cancellous bone can promote scaffold revascularization, which then accelerates cell proliferation. This study presents a parameterized design and fabrication method for cranial scaffold construction. A native human cranial sample was first scanned using micro computed tomography (CT), followed by 3D reconstruction, after which the internal structure of the bone trabecula was created. Based on an extracted negative bone trabecula model, the design components of "cavity", "connecting pipe" and "spatial framework" were proposed to describe the scaffold model. Then, by using the parameterized component model and an assembly and deformation algorithm, the bionic scaffold was designed. Its porous distribution, connection, porosity and area size were easily controlled. Finally, a biomaterial scaffold case was fabricated using a gelcasting process, and cell culture testing was performed in vitro to verify the scaffold's biocompatibility. The results show that the scaffold can promote cell growth and that cells accumulate in the form of a mass within three days.

CCL18 promotes the invasion and metastasis of breast cancer through Annexin A2.

Chemokine (C­C motif) ligand 18 (CCL18) is derived from breast tumor­associated macrophages (TAMs), which are primarily a macrophage subpopulation with an M2 phenotype. CCL18 binds to its receptor, PYK2 N­terminal domain interacting receptor 1 (Nir1), and promotes tumor progression and metastasis by inducing epithelial­mesenchymal transition (EMT) via the PI3K/Akt/GSK3ß/Snail signaling pathway in breast cancer cells. Recent research shows that Annexin A2 (AnxA2) plays a significant role in the invasion, metastasis, angiogenesis, proliferation, F­actin polymerization and multidrug resistance to chemotherapy of breast cancer. The present study aimed to elucidate the molecular mechanisms by which CCL18 promotes breast cancer progression through AnxA2 which are not fully understood. Western blot analysis showed that the expression of AnxA2 was upregulated in highly invasive breast cancer cell lines and invasive ductal carcinoma. Furthermore, through chemotaxis, scratch, Matrigel invasion, and spontaneous metastasis assays, it was demonstrated that AnxA2 enhanced the invasion of breast cancer cells and the metastasis of human breast cancer cells to lungs of SCID mice with CCL18 stimulation. Cellular F­actin measurement assay showed that reduction of AnxA2 suppressed CCL18­induced F­actin polymerization though phosphorylation of integrin ß1 in breast cancer cells. Immunofluorescence and western blot analysis revealed that AnxA2 promoted CCL18­induced EMT via the PI3K/Akt/GSK3ß/Snail signaling pathway, and LY294002 inhibited the phosphorylation of AnxA2 in vitro. In brief, AnxA2, as a downstream molecule of Nir 1 binding to CCL18, promotes invasion and metastasis by EMT through the PI3K/Akt/GSK3ß/Snail signaling pathway in breast cancer. This study suggests that AnxA2 is a potential anti­invasion/metastasis target for therapeutic intervention in breast cancer.

A mosaic structure multi-level vascular network design for skull tissue engineering.

In human skull tissue engineering scaffolds, cell growth and osteogenesis are limited due to the lack of vascular structure. Therefore, a mosaic structure vascular parameterized design method is proposed according to the scanning characteristics of the diploic vein. Using micro-CT scans of skull samples, the features of the diploic vein were extracted, and a multi-level vascular network model was established based on a power diagram. Considering the characteristics of blood flow in the veins, finite element analysis (FEA) of the fluid-solid coupling was established to analyze the effect of blood on vessels with four-level mosaic structures. The results showed that the deformation and stress distribution of vessels were reasonable, and the blood pressure, velocity and shear stress in the designed vascular structure could meet the cell growth requirements. The mosaic structure was prepared by PDMS and cultured in vitro using HUVECs. It was found that most of the cells survived after 48 h, and some cells were attached to the surface mosaic structure. In this method, different levels of vessels nest together, with a curvature that matches the shape of the skull, forming a similar morphology to the native diploic vein, and the local structures can be adjusted flexibly. This mosaic structure vascular design method can be used for network vascular design and experimental studies in hard tissues.

Development of a novel HPLC method for the determination of the impurities in desonide cream and characterization of its impurities by 2D LC-IT-TOF MS.

A novel HPLC method for the determination of the impurities in desonide cream was established and validated for the further improvement of the official monograph in USP. Desonide was well resolved from the photodegradation impurity, which overlapped with desonide in USP method. The method was validated in accordance to the regulatory guidelines recommended by the International Conference on Harmonisation and this validation included specificity, limit of detection, limit of quantification, linearity and accuracy. Four degradation impurities in desonide cream were characterized by a trap-free two-dimensional liquid chromatography coupled to high resolution ion trap/time-of-flight mass spectrometry (2D LC-IT-TOF MS) in positive mode of electrospray ionization. Through the multiple heart-cutting 2D LC approach and online demineralization technique, the problem of incompatibility between non-volatile salt mobile phase and mass spectrometry was solved completely, and the TIC chromatogram of LC-MS could be in conformity with the LC chromatogram of the official analytical method in the peak sequence of impurities. In the first dimension, the column was Phenomenex Kinetex C8 (4.6 mm × 150 mm, 2.6 µm) with a non-volatile salt mobile phase. In the second dimension, the column was Shimadzu Shim-pack GISS C18 (50 mm × 2.1 mm, 1.9 µm) with a volatile salt mobile phase. The structures of four degradation impurities in desonide cream were deduced based on the HPLC-MSn data. The established method in this study was simple and reliable for routine quality control of desonide cream.

Dock1 promotes the mesenchymal transition of glioma and is modulated by MiR-31.

AIMS: This research aimed to examine the relationship between Dock1 and miR-31 and to determine the effect of miR-31 on the mesenchymal transition and invasiveness of glioma. METHODS: Real-time PCR was used to measure the expression of miR-31 and other RNAs. The transfection was used to manipulate the expression levels of Dock1 and miR-31 in cancer cells. Western blot was used to detect the expression of Dock1 and other related proteins. Wound healing, Matrigel invasion and chemotaxis assays were performed to detect the invasion and migration of glioma cell lines. The actual binding site of miR-31 to the 3'-untranslated region of Dock1 was confirmed through luciferase assay and RNA immunoprecipitation. Methylation-specific PCR was performed to detect the methylation level of miR-31 in both glioma cell lines and tissues. RESULTS: Dock1 can promote the IL8-induced chemotaxis and mesenchymal transition of glioma cells through the NF-κB/Snail signalling pathway. The protein levels of Dock1 in glioma cell lines and clinical specimens were negatively correlated with miR-31 expression, and Dock1 was directly targeted by miR-31. Animal experiments showed that Dock1 downregulation and miR-31 overexpression reduced glioma cell invasion. Investigation of the underlying molecular mechanism revealed that miR-31 downregulation was attributable to the hypermethylation of the promoter region of miR-31 in glioma cells. CONCLUSION: Dock1 modulation by miR-31 plays an important function in glioma invasion both in vitro and in vivo. This study provides new insights into the invasion of glioma cells and might therefore contribute to the development of new antiglioma strategies.

A new 3D contour extraction method for tooth cavity in a dental CAD/CAM system.

In dental CAD/CAM system, tooth restoration produces customized tooth with a prepared cavity, while the prosthetic tooth fitting is firstly determined by the contour feature of the cavity, the cavity contour extraction of the tooth is one of the important issue. In order to accurately extract the cavity contour, a new Three-Dimension (3D) optimal path searching algorithm based on Intelligent Scissors theory is presented. In this algorithm, the 3D tooth is firstly formulated as a weighted model, by calculating the minimum weigh sum of the local cost from a start point to an end point in the cavity edge, the initial optimal contour can be acquired. Then through restricting the path searching range and searching direction, a desired contour can be extracted dynamically. The cases study results show that the algorithm produces a 3D mathematically piece-wise optimal contour on the cavity edge, which can be used directly for tooth design. This method simplifies the tooth design processes and increases the design efficiency.