GM-CSF及CBS在肝损伤中的研究进展

肝损伤(liver injury)是指基因遗传或外部原因诱发的肝脏功能异常性疾病.临床表现为食欲不振、乏力、恶心、黄疸、疲乏等,严重者将出现肝功能衰竭,致死风险极高.在交通肇事、暴力犯罪及意外事件中,肝由于体积大、位置固定、质地脆弱、血运丰富等原因,往往是最容易发生损伤的器官之一,肝损伤后的死亡率可高达10.5％～25％[1].随着时间的变化,肝损伤的程度、病理改变、GM-CSF等相关细胞因子及CBS等相关酶的表达水平也会进一步变化.肝损伤后,由于肝内部环境稳态的破坏,器官的状态、结构、各种蛋白的转录水平、蛋白及细胞因子的表达变化水平也会发生一定程度的改变.因此定性定量地分析这些变化,找到时间相关性强的特异性指标,对于指导法医学的实践具有重要的作用.因此在法医学鉴定中,通过肝脏损伤及病变程度的改变,明确肝损伤病变与死亡时间的关系有利于判断事件或案件性质,并有助于进一步对责任方的认定.     

Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

The surface carboxyl group of carbonaceous microspheres effects on the synthesis and structure of SiOC ceramics

In this study, C/SiOC and C/SiO₂ composites were prepared by using carbonaceous microspheres with different surface functional groups. Carbonaceous microspheres based on hydrothermal reaction of glucose contains hydroxyl group, while the surface carboxyl group increases after NaOH etching. The hydroxyl group increases the oxygen-enriched structural units of SiOC ceramics, and the C spheres are closely enwrapped in SiOC matrix after pyrolysis at 900 °C. However, the interfacial reaction of surface carboxyl with Si–OH results in the formation of cristobalite SiO₂, and C spheres are not only encased inside the SiOC matrix, but also dispersed outside of SiOC ceramics. After removal of C via calcination at 500 °C for 5 h, C/SiOC and C/SiO₂ composites are transformed into amorphous SiO₂ and cristobalite SiO₂, respectively. The thermogravimetric analysis indicates the oxidation resistance of SiOC is superior to that of C and SiO₂.     

Deacetylated Cellulose Acetate/Polyurethane Composite Nanofiber Membranes with Highly Efficient Oil/Water Separation and Excellent Mechanical Properties

Nowadays, oil pollution has become more serious, which causes great threats both to the ecological environment and human life. In this study, a novel type of multifunctional deacetylated cellulose acetate/polyurethane (d-M_CA:M_TPU) composite nanofiber membranes for oil/water separation are successfully fabricated by electrospinning, which show super-amphiphilicity in air, super-hydrophilicity in oil, and oleophobicity in water. All the d-M_CA:M_TPU composite nanofiber membranes with different mass ratios can be used as water-removing, oil-removing, and emulsion separation substance only by gravity driving force. The highest separation flux for water and oil reaches up to 37 000 and 74 000 L m⁻² h⁻¹, respectively, and all the separation efficiencies are more than 99%. They have outstanding comprehensive mechanics performance, which can be controlled by simply adjusting the mass ratios. They show excellent antifouling and self-cleaning ability, endowing powerful cyclic stability and reusability. Those results show that d-M_CA:M_TPU composite nanofiber membranes have great application prospects in oil/water separation.     

Crystallization,structure, and enhanced mechanical property of ethylene-octene elastomer crosslinked with dicumyl peroxide

Crosslinking of polyolefin elastomer (POE, ENGAGE™ 8480) with Dicumyl Peroxide (DCP) can have effects on its crystallization dynamics, crystal structure, and properties. The POE crosslinked uniformly has significantly lower crystalline ability than the one with only amorphous phase crosslinked, which, in turn, has weaker crystalline ability than neat POE. The crystallinity and melting point depend on how the POE is crosslinked. The neat POE and POE crosslinked in amorphous phase only, are investigated with DSC and in-situ tensile/synchrotron radiation (WAXD/SAXS). In situ tensile/synchrotron X-ray during a uniaxial stretching process indicates that severe crystal fragmentation is observed at a strain around 45%, and with further increase in strain. The stress in the crosslinked POE is significantly larger than neat POE. For both samples, crystal orientation increases sharply within the strain range up to 88% where orientation-induced new crystals aligned in stretching direction are observed. The long period increases more in stretching direction for the crosslinked POE, consistent with larger stress in this sample, and the stress difference is more pronounced at large strains (27.3 vs. 10.9 MPa at a strain 435%). Permanent set of the crosslinked POE is smaller, consistent with less oriented crystals observed after the test for permanent set.     

Simultaneous fractionation of multiple classes of polyphenols from honeybush tea using solid-phase extraction

The structural diversity of polyphenols and the inherent limitations of current extraction techniques pose a challenge to extract polyphenols using a simple and green method. Hence, in this study, a method was developed to simultaneously fractionate multiple classes of polyphenols by only varying ethanol-water solutions. Honeybush tea, which is rich in polyphenols, was selected as a model for this study. Solvent extraction followed by solid-phase extraction (SPE) was developed to obtain a polyphenol-rich fraction from six honeybush samples. Based on a gradient elution programme (10%, 30%, 50%, 70% and 90% (v/v) ethanol-water solution) of SPE, the Strata X cartridge showed a better recovery of most targeted polyphenols under 0.9 mL of the drying volume and 1 mL min⁻¹ of the dispensing speed. The elution programme for fractionating most polyphenols was as follows: single elution with 50% ethanol, followed by twice elution with 70% ethanol. The antioxidant capacity was used to analyse the differences among the polyphenol-rich fractions from six honeybush samples. Principal component analysis (PCA) revealed that unfermented C. genistoides (GG) has the greatest antioxidant capacity among the honeybush species studied. Additionally, mangiferin, isomangiferin and vicenin-2 were the main contributors to the antioxidant capacity in six honeybush fractions according to the correlation study.     

A Highly Sensitive,Reversible, and Bidirectional Humidity Actuator by Calcium Carbonate Ionic Oligomers Incorporated Poly(Vinylidene Fluoride)

Sensitivity and multi-directional motivation are major two factors for developing optimized humidity-response materials, which are promising for sensing, energy production, etc. Organic functional groups are commonly used as the water sensitive units through hydrogen bond interactions with water molecules in actuators. The multi-coordination ability of inorganic ions implies that the inorganic ionic compounds are potentially superior water sensitive units. However, the particle forms of inorganic ionic compounds produced by classical nucleation limit the number of exposed ions to interact with water. Recent progress on the inorganic ionic oligomers has broken through the limitation of classical nucleation, and realized the molecular-scaled incorporation of inorganic ionic compounds into an organic matrix. Here, the incorporation of hydrophilic calcium carbonate ionic oligomers into hydrophobic poly(vinylidene fluoride) (PVDF) is demonstrated. The ultra-small calcium carbonate oligomers within a PVDF film endow it with an ultra-sensitive, reversible, and bidirectional response. The motivation ability is superior to other bidirectional humidity-actuators at present, which realizes self-motivation on an ice surface, converting the chemical potential energy of the humidity gradient from ice to kinetic energy.     

Marine Phospholipids from Fishery By-Products Attenuate Atherosclerosis

In this study, the anti-atherosclerotic properties of three marine phospholipids (MPLs) extracts from fishery by-products including codfish roe, squid gonad, and shrimp head are verified. Their effects on key factors involved in atherosclerosis are examined and compared to explore whether the differences in their constitutions lead to the differences in the function. All three MPLs dampen oxidation of low- density lipoproteins (LDL) in vitro. Treating RAW264.7 macrophages and HUVECs endothelial cells with each MPLs ranging 10–100 µg mL⁻¹ does not decrease cell viability, yet ox-LDL caused cytotoxicity of both cells are alleviated by 50 or 100 µg mL⁻¹ MPLs treatment. In addition, the three MPLs reduce ox-LDL induced macrophage foam-like transition, mainly through inhibition of lipid uptake. Of the three MPLs, the one from squid gonad exhibits the best effect. On the other hand, all three MPLs modulate inflammatory responses, equally, by inhibiting the adhesion of monocytes to endothelial cells, and decreasing secretion of pro-inflammatory cytokines IL-6 and MCP-1. Using a high-cholesterol diet induced zebrafish model, it is found that all three MPLs, especially the one from squid gonad, alleviates cholesterol accumulation in early plaques, and decreases total cholesterol as well as lipid peroxide in vivo. Practical Applications: As a way of making the best of the increasingly scarce marine resources, valuable lipid components can be recovered from by-products and wastes from the fishery industry. Here, we tested the anti-atherosclerotic effects and the mechanisms of three MPLs extracted from codfish roe, squid gonad, and shrimp head. Our study provides further evidence that marine phospholipids extracted from fishery by-products could protect against atherosclerosis, and helps to elucidate the structure-function relationship of MPLs.     

Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.     

Enhanced strains of Nb-doped BNKT-4ST piezoelectric ceramics via phase boundary and domain design

A strategy that constructs the morphotropic phase boundary and manipulates the domain structure has been used to design the component of 0.96[Bi_0.5(Na_0.84K_0.16)_0.5Ti_(1-x)Nb_xO₃]-0.04SrTiO₃ (BNKT-4ST-100xNb) to enhance the strain properties for actuator application. Non-equivalent Nb⁵⁺ donor doping modulates the phase transition from the mixture of rhombohedral and tetragonal phases to the pseudocubic phase and results in the coexistence of multiple phases. Moreover, the high-resolution TEM confirms the existence of polar nano regions that contribute to the macroscopic relaxor behaviour. The size of the domains is reduced with increasing Nb⁵⁺, resulting in an enhanced relaxor behaviour. The ferroelectric-relaxor transition temperature decreases from 85 to below 30 °C, implying a non-ergodic to ergodic relaxor transition. An improved strain of 0.56% and a giant normalized strain of 1120 pm/V were achieved for BNKT-4ST-1.5Nb, which were attributed to the unique domain structure in which nanodomains are embedded in an undistorted cubic matrix. Ferroelectric, antiferroelectric, and relaxor phases coexist. As the electric field is large enough, a reversible phase transition occurs. Furthermore, good temperature stability was obtained due to the stability of the nanodomains, and no degradation in strains was observed even after 10⁴ cycles, which may originate from the reversible phase transition and dynamic domain wall. The results show that this design strategy offers a reference way to improve the strain behaviour and that BNKT-4ST-100xNb ceramics could be a potential material for high-displacement actuator applications.