M1表型的小胶质细胞外泌体对血脑屏障功能的影响

目的 研究M1表型的小胶质细胞外泌体（M1 microglia-derived exosome,M1-exo）对体外血脑屏障（blood-brain barrier,BBB）功能及血管内皮细胞间紧密连接蛋白表达的影响。方法 用脂多糖（lipopolysaccharide,LPS）刺激小鼠小胶质细胞来源的细胞系BV2细胞,流式技术检测其向M1型极化情况,分离提取外泌体。用小鼠脑微血管内皮细胞系b.End3细胞与原代培养的小鼠星形胶质细胞构建体外BBB模型,随机分为3组：b.End3细胞正常培养组（b.End3组）、b.End3细胞+25 μg/mL正常BV2细胞来源外泌体（BV2-derived exosome,BV2-exo）组（b.End3+BV2-exo组）、b.End3细胞+25 μg/mL M1表型的小胶质细胞来源外泌体组（b.End3+M1-exo组）。按实验分组将不同来源外泌体与BBB模型共培养,检测各组的跨膜电阻（trans-endothelial electrical resistance,TEER）、荧光黄通过率,免疫印迹法（Western blot,WB）检测紧密连接复合物蛋白Claudin-1、Occludin、ZO-1及JAM蛋白的表达。结果 ①小胶质细胞向M1型极化成功,其细胞标志物CD16/32阳性率较对照组明显升高（P=0.023）;②与M1-exo共培养后,体外BBB模型的TEER明显下降（P=0.000）,对荧光黄的透过率明显增加（P=0.000）;③与b.End3组和b.End3 + BV2-exo组相比,b.End3+M1-exo组的Claudin-1、Occludin及ZO-1蛋白的表达水平明显下降。结论 M1-exo可以破坏BBB的完整性,影响其功能。     

鞍区肿瘤术后并发抗利尿激素异常分泌综合征的观察与护理

目的:探讨鞍区肿瘤术后并发抗利尿激素异常分泌综合征(SIADH)患者的观察与护理方法。方法:对62例并发SIADH患者的资料进行回顾性临床分析。结果:患者血清钠均<130mmol/L;血浆渗透压<270msom/L;尿渗透压/血浆渗透压>1;尿钠>20mmol/L,给予增大皮质醇药物剂量或予以ACTH、限水、限钠或补钠等治疗,患者在2周左右恢复正常。结论:密切观察患者生命体征、意识变化,监测患者尿量、尿比重和血清钠、血尿渗透压等实验室指标,有助于SIADH的诊断与治疗,加强对患者饮食及预防并发症等护理,可降低病残率及病死率,促进患者早日康复。     

The variants in PTPRB,TRAF3IP3, and DISC1 genes were associated with Graves’ disease in the Chinese population

Previously, a case series study was conducted on our part in which 5 patients with Graves’ disease (GD) were collected from a 3-generation family to screen for susceptibility genes responsible for GD. The single nucleotide variants of Microtubule-associated protein 7 domain containing 2 c. 452C > T, p. Ala151Val, Solute carrier family 1 member 7 c. 1204C > T, p. Arg402Cys, tumor necrosis factor receptor-associated factor 3 interacting protein 3 (TRAF3IP3) c. 209A > T, p. Asn70Ile, protein tyrosine phosphatase receptor type B (PTPRB) c. 3472A > G, p. Ser1158Gly, Phosphoinositide-3-kinase regulatory subunit 3 c. 121C > T, p. Pro41Ser, disrupted in schizophrenia 1 (DISC1), c. 1591G > C p. Gly531Arg were associated with the familial GD. We then further confirmed these variants and investigated whether other mutations render susceptibility to GD. The case-control study collected patients with sporadic GD or no GD family history. A snapshot program was used for genotyping the selected SNPs in 235 GD patients (GD group 1) and 284 healthy patients (control group). Furthermore, another 184 GD patients were recruited (GD group 2) to sequence the specified exons of these genes. The sequenced data was compared with Chinese Millionome Database (CMDB). Several variants of PTPRB, phosphoinositide-3-kinase regulatory subunit 3, TRAF3IP3, and DISC1 were found in GD group 2 but not in CMDB. Moreover, the allele frequency of SNP rs2076150 (TRAF3IP3) and rs2492367 DISC1 in GD group 2 was significantly higher than that of in CMDB (all P < .05). When the control group or CMDB was set as a reference group, a significantly higher frequency in alter allele C of SNP rs186466118 PTPRB was observed in GD group 1 and GD group (constituted by GD group 1 and GD group 2). Equally importantly, there was a correlation between the allele C of SNP rs186466118 and the increased risk of GD susceptibility (all P < .05). PTPRB, TRAF3IP3, and DISC1 may be susceptibility genes for GD, and more variants of PTPRB, TRAF3IP3, and DISC1 were found in GD patients.     

Investigation on the Fatigue Crack Propagation of Medium-Entropy Alloys with Heterogeneous Microstructures

The behavior and the mechanism of fatigue crack propagation in CrCoNi medium-entropy alloys (MEAs) with heterogeneous microstructures were investigated in this paper. After cold-rolling and recrystallization annealing at different temperatures and times, five sets of heterostructured specimens were acquired with different recrystallization levels. Then, the structure characterizations of these five sets of specimens were carried out by nanoindentation testing and electron back-scatter diffraction (EBSD) mapping. Finally, the fatigue crack propagation tests were conducted on single edge crack specimens of these different heterogeneous microstructures. The experimental results indicate that the crack propagation rates of specimens with partial recrystallization microstructures are higher than those with complete recrystallization microstructures, and the effect on fatigue crack thresholds of these specimens is the opposite. The fatigue cracks grow along the slip planes or twin boundaries in recrystallization grains (RGs), which induced crack deflections and the roughness-induced crack closure effect. For this reason, the area percentage of recrystallization and the grain size of RGs have a great effect on the value of the fatigue crack growth threshold.     

An Experimental and Numerical Study of the Influence of Temperature on Mode II Fracture of a T800/Epoxy Unidirectional Laminate

Studies on mode II fracture have promoted the establishment of the delamination theory for unidirectional composite laminates at room temperature. However, under thermal conditions, the fracture behavior of composite laminates will exhibit certain differences. The delamination theory should be extended to consider the temperature effect. To achieve this goal, in this study, the mode II static delamination growth behavior of an aerospace-grade T800/epoxy composite is investigated at 23 °C, 80 °C and 130 °C. The mode II fracture resistance curve (R-curve) is experimentally determined. A fractographic study on the fracture surface is performed using a scanning electron microscope (SEM), in order to reveal the failure mechanism. In addition, a numerical framework based on the cohesive zone model with a bilinear constitutive law is established for simulating the mode II delamination growth behavior at the thermal condition. The effects of the interfacial parameters on the simulations are investigated and a suitable value set for the interfacial parameters is determined. Good agreements between the experimental and numerical load–displacement responses illustrate the applicability of the numerical model. The research results provide helpful guidance for the design of composite laminates and an effective numerical method for the simulation of mode II delamination growth behavior.     

Evaluation of Pozzolanic and Alkali-Activated Reactivity of Low-Purity Calcium Bentonite

Alkali-activated cement (AAC) is a sustainable building material with low carbon emissions, but it has a growing demand for raw materials. In this study, the potential of low-purity modified calcium bentonite (CB) as a raw material for AAC was evaluated. The thermodynamic changes and pozzolanic properties of calcined CB were determined using X-ray diffraction (XRD), thermogravimetry-differential thermal analysis (TG-DTA), zeta potential, and a strength activity index (SAI) test. The compressive strength test, scanning electron microscopy–energy dispersive spectrometer (SEM-EDS), and Fourier-transform infrared (FTIR) spectroscopy were performed to examine the compatibility between CB and AAC. It was revealed that CB is a low-purity clay with low-pozzolanic activity. Calcination enhanced its pozzolanic activity, and the optimum temperature is 750 °C. The incorporation of modified CB improved the mechanical properties of AAC, and low-temperature modified CB had better compatibility with AAC than the high-temperature modified CB. Calcination at 150 °C had little effect on the structure of CB, and the water absorption of montmorillonite increased the ion concentration, increasing the rate and degree of hydration. Furthermore, low-temperature calcination had a dissolution–precipitation effect, resulting in leaf-like CaO·SiO₂·H₂O (C-S-H) gels, whereas the high-temperature calcination of CB was very reactive, resulting in flower-like C(N)-S-H gels.     

Effect of Layered Double Hydroxides on the Deterioration Process of Cement Paste under Sulfate Attack

This study investigated the effect of layered double hydroxides (LDHs) on the deterioration process of cement paste in the sulfate environment. Cement pastes with the addition of original and calcined LDHs at 2.5 wt.% and 5.0 wt.% of cement were exposed to Na₂SO₄ solution for 360 days. The macroscopic performance of the cement paste was assessed based on mass variation, porosity, compressive strength, and content of sulfate ions. Furthermore, the microhardness, microstructures, and composition of the degraded pastes were examined using Vickers hardness (HV), mercury intrusion porosimetry (MIP), scanning electron microscope (SEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The results indicate that cement paste incorporated with LDHs can mitigate the corrosion caused by sulfate effectively, especially in the case of calcined LDHs (C-LDHs), which primarily increase the adsorption of sulfate. Compared with the control specimen, the 180 d compressive strength loss ratio of specimens with 2.5 wt.% and 5.0 wt.% of C-LDHs decreased by 63.66% and 80.51%, respectively. Moreover, LDHs can reduce the amount of ettringite crystals, densify the microstructure, and refine the pore structure to mitigate the cement paste’s sulfate corrosion significantly. Compared with the control specimen, the 180 d harmful pore volume fraction of specimens laced with 2.5 wt.% and 5.0 wt.% C-LDHs decreased by 43.77% and 54.51%, respectively. In terms of the content of C-LDHs, an optimal content of C-LDHs could ensure the dominant effect of adsorption, while excessive C-LDHs could refine pores. In addition, Vickers hardness has an excellent correlation with compressive strength, which could precisely predict the compressive strength. Moreover, by combining the Vickers hardness distribution and content distribution of sulfate ions, the cross-section of the paste could be classified into four regions to evaluate the deterioration process accurately: the degraded zone, the strengthened zone, the invaded zone, and the intact zone.     

Modeling HPV-Associated Disease and Cancer Using the Cottontail Rabbit Papillomavirus

Approximately 5% of all human cancers are attributable to human papillomavirus (HPV) infections. HPV-associated diseases and cancers remain a substantial public health and economic burden worldwide despite the availability of prophylactic HPV vaccines. Current diagnosis and treatments for HPV-associated diseases and cancers are predominantly based on cell/tissue morphological examination and/or testing for the presence of high-risk HPV types. There is a lack of robust targets/markers to improve the accuracy of diagnosis and treatments. Several naturally occurring animal papillomavirus models have been established as surrogates to study HPV pathogenesis. Among them, the Cottontail rabbit papillomavirus (CRPV) model has become known as the gold standard. This model has played a pivotal role in the successful development of vaccines now available to prevent HPV infections. Over the past eighty years, the CRPV model has been widely applied to study HPV carcinogenesis. Taking advantage of a large panel of functional mutant CRPV genomes with distinct, reproducible, and predictable phenotypes, we have gained a deeper understanding of viral–host interaction during tumor progression. In recent years, the application of genome-wide RNA-seq analysis to the CRPV model has allowed us to learn and validate changes that parallel those reported in HPV-associated cancers. In addition, we have established a selection of gene-modified rabbit lines to facilitate mechanistic studies and the development of novel therapeutic strategies. In the current review, we summarize some significant findings that have advanced our understanding of HPV pathogenesis and highlight the implication of the development of novel gene-modified rabbits to future mechanistic studies.