Self-assembled morphologies of polyelectrolyte-grafted nanoparticles directed by oppositely charged polymer matrices

Self-assembled structure of polymer grafted nanoparticles is an interesting and growing subject in the field of hybrid electronics and high energy density materials. In light of this, the self-assembled morphologies of polyelectrolyte (PE) sparsely grafted nanoparticles tuned by oppositely charged matrix chains are studied using molecular dynamics simulations. Our focus is to elucidate the effect of matrix chain polymerization on modulating the stretching properties of tethered PE layers, on the self-assembled structuring of nanoparticles. Through varying the matrix chain length and stiffness as well as electrostatic interaction strength, rich phase behaviors of PE coated nanoparticles are predicted, including spherical micelle-like structures being preferred with short matrix chains and percolating network morphologies favored with long matrix chains, which is more pronounced with an enhanced matrix chain rigidness. To pinpoint the mechanisms of self-assembled structure formation, the thickness of grafted layers, the gyration radius of tethered chains, and pair correlation functions between nanoparticles are analyzed carefully. Additionally, electrostatic correlations, manifested as the bridging via matrix chains, are examined by identifying three states of matrix PE chains. Our simulation results may be useful for designing smart polymer nanocomposites based on PE coated nanoparticles.

Self-assembled structure of polymer grafted nanoparticles is an interesting and growing subject in the field of hybrid electronics and high energy density materials.     

警惕“高功能陷阱”——双相抑郁患者的过度状态期望

维持病情长期稳定是双相障碍治疗的关键,而准确判断患者的疾病状态是维持治疗的重点和难点。过度状态期望常见于双相抑郁患者,通过影响患者对自身疾病状态的判断,最终干扰临床决策,此现象应当引起高度关注。本文就双相障碍患者过度状态期望的现象和可能的机制进行探讨,为有关诊疗和研究提供思路。     

学习投入对农村订单定向医学生核心能力的影响及专业承诺的调节作用

目的：探索学习投入、专业承诺对农村订单定向医学生核心能力的影响,为提升基层卫生人才队伍的质量提供理论参考。方法：通过多阶段整群抽样方法,抽取S省两所医学院校的520名农村订单定向医学生作为研究对象进行调查。采用分层回归法分析学习投入对农村订单定向医学生核心能力的影响,简单斜率检验分析专业承诺对前述两者关系的调节效应。结果：S省农村订单定向医学生核心能力总体平均得分为(3.39±0.549);学习投入对农村订单定向医学生核心能力存在显著正向影响(β=0.358),且专业承诺对前述两者关系存在调节效应,该调节效应使得学习投入对核心能力的影响变强(β=0.206)。结论：完善农村订单定向医学生培养政策,严把录取质量,加大基层基地的建设与投入,重视学生职业素质教育,提升核心能力。     

UBE2C promotes the progression of pancreatic cancer and glycolytic activity via EGFR stabilization-mediated PI3K-Akt pathway activation

BackgroundPancreatic cancer (PC) is among the most prevalent and deadliest endocrine tumors, yet the mechanisms governing its pathogenesis remain to be fully clarified. While ubiquitin-conjugating enzyme E2C (UBE2C) has been identified as an important oncogene in several cancers, its importance in PC has yet to be established.MethodsUBE2C expression in PC tumor samples and cell lines was examined via quantitative real-time polymerase chain reaction (qRT-PCR), while appropriate commercial kits were used to assess lactate production, ATP generation, and the uptake of glucose.ResultsUBE2C was found to be upregulated in PC patient tumors and correlated with poorer survival outcomes. In PC cell lines, the silencing of this gene suppressed the malignant activity of cells, thus supporting its identification as an oncogene in this cancer type. Mechanistically, UBE2C was found to promote enhanced matrix metalloproteinase (MMP) protein expression via activating the PI3K-Akt pathway. Moreover, it was found to bind to the epidermal growth factor receptor (EGFR), stabilizing it and driving additional PI3K-Akt pathway activation. UBE2C knockdown in PC cells impaired their uptake of glucose and their ability to produce lactate and ATP.ConclusionsIn conclusion, the results of this study support a role for UBE2C as a driver of metastatic PC progression owing to its ability to bind to EGFR and to induce signaling via the PI3K-Akt pathway.     

Neoadjuvant chemotherapy endows CD9 with prognostic value that differs between tumor and stromal areas in patients with pancreatic cancer

BackgroundThe selective pressure imposed by chemotherapy creates a barrier to tumor eradication and an opportunity for metastasis and recurrence. As a newly discovered stemness marker of pancreatic ductal adenocarcinoma (PDAC), the impact of CD9 on tumor progression and patient''s prognosis remain controversial.MethodsA total of 179 and 211 PDAC patients who underwent surgical resection with or without neoadjuvant chemotherapy, respectively, were recruited for immunohistochemical analyses of CD9 expression in both tumor and stromal areas prior to statistical analyses to determine the prognostic impact and predictive accuracy of CD9.ResultsThe relationship between CD9 and prognostic indicators was not significant in the non‐neoadjuvant group. Nevertheless, CD9 expression in both tumor (T‐CD9) and stromal areas (S‐CD9) was significantly correlated with the clinicopathological features in the neoadjuvant group. High levels of T‐CD9 were significantly associated with worse OS (p = 0.005) and RFS (p = 0.007), while positive S‐CD9 showed the opposite results (OS: p = 0.024; RFS: p = 0.008). Cox regression analyses identified CD9 in both areas as an independent prognostic factor. The T&S‐CD9 risk‐level system was used to stratify patients with different survival levels. The combination of T&S‐CD9 risk level and TNM stage were accurate predictors of OS (C‐index: 0.676; AIC: 512.51) and RFS (C‐index: 0.680; AIC: 519.53). The calibration curve of the nomogram composed of the combined parameters showed excellent predictive consistency for 1‐year RFS. These results were verified using a validation cohort.ConclusionNeoadjuvant chemotherapy endows CD9 with a significant prognostic value that differs between tumor and stromal areas in patients with pancreatic cancer.     

Development and evaluation of time‐resolved fluorescent immunochromatographic assay for quantitative detection of SARS‐CoV‐2 spike antigen

BackgroundThe spread of COVID‐19 worldwide caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has necessitated efficient, sensitive diagnostic methods to identify infected people. We report on the development of a rapid 15‐minute time‐resolved fluorescent (TRF) lateral flow immunochromatographic assay for the quantitative detection of the SARS‐CoV‐2 spike protein receptor‐binding domain (S1‐RBD).ObjectivesOur objective was to develop an efficient method of detecting SARS‐CoV‐2 within 15 min of sample collection.MethodsWe constructed and evaluated a portable, disposable lateral flow device, which detected the S1‐RBD protein directly in nasopharyngeal swab samples. The device emits a fluorescent signal in the presence of S1‐RBD, which can be captured by an automated TRF instrument.ResultsThe TRF lateral flow assay signal was linear from 0 to 20 ng/ml and demonstrated high accuracy and reproducibility. When evaluated with clinical nasopharyngeal swabs, the assay was performed at >80% sensitivity, >84% specificity, and > 82% accuracy for detection of the S1‐RBD antigen.ConclusionThe new S1‐RBD antigen test is a rapid (15 min), sensitive, and specific assay that requires minimal sample preparation. Critically, the assay correlated closely with PCR‐based methodology in nasopharyngeal swab samples, showing that the detected S1‐RBD antigen levels correlate with SARS‐CoV‐2 virus load. Therefore, the new TRF lateral flow test for S1‐RBD has potential application in point‐of‐care settings.     

Using a two-step method of surface mechanical attrition treatment and calcium ion implantation to promote the osteogenic activity of mesenchymal stem cells as well as biomineralization on a β-titanium surface

Surface treatment is known as a very efficient measure by which to modulate the surface properties of biomaterials in terms of grain structure, topography, roughness and chemistry to determine the osseointegration of implants. In this work, a two-step method of surface modification was employed to impart high osteogenic activity and biomineralization capacity on a Ti–25Nb–3Mo–2Sn–3Zr alloy (a type of β-titanium named TLM). The preliminary surface mechanical attrition treatment (SMAT) refined the average grain size from 170 ± 19 μm to 74 ± 8 nm in the TLM surface layer and promoted the surface to be much rougher and more hydrophilic. The subsequent Ca-ion implantation did not change the surface roughness and topography obviously, but enhanced the surface wettability of the SMAT-treated TLM alloy. The in vitro evaluations of the adhesion, proliferation, osteogenic genes (RUNX2, ALP, BMP-2, OPN, OCN and COL-I) and protein (ALP, OPN, OCN and COL-I) expressions, as well as extracellular matrix (ECM) mineralization of mesenchymal stem cells (MSCs) revealed that the initial SMAT-treated sample significantly enhanced the adhesion and osteogenic functions of MSCs compared to an untreated TLM sample, and the subsequent introduction of Ca ions onto the SMAT-derived nanograined sample further promotes the MSC adhesion, proliferation, osteo-differentiation and ECM mineralization due to the adsorption of more proteins such as laminin (Ln), fibronectin (Fn) and vitronectin (Vn) on the surface, as well as the increase in extracellular Ca concentrations. In addition, the biomineralization capacity of the samples was also evaluated by soaking them in simulated bodily fluid (SBF) at 37 °C for 28 days, and the results showed that the Ca-ion implanted sample significantly boosted the deposition of Ca and P containing minerals on its surface, which was associated with the generation of more Ti–OH groups on the surface after ion implantation. The combination of the SMAT technique and Ca-ion implantation thus endowed the TLM alloy with outstanding osteogenic and biomineralization properties, providing a potential means for its future use in the orthopedic field.

Combination of the SMAT technique and Ca-ion implantation produced a β-titanium alloy with a bioactive surface layer, which was proved to effectively promote the osteogenic activity of MSCs and Ca–P mineral deposition in vitro.     

基于虚拟切片的体视学模型仿真与分析

目的 建立虚拟组织切片的体视学模型,并以软件系统作为实现手段,模拟虚拟切片过程,为体视学的理论提供一个客观实证工具.方法 以数学手段描述组织切片可能出现的二维形态特征,模拟切片过程,将所得到的数据进行数值分析,与经验公式进行了拟合比较.结果 基于此算法可实现虚拟随机模拟切片,经拟合优度检验数据分布的均匀性检验通过率达94.5％以上.独立性检验通过率达92％以上.且均符合正态性要求.经线性和曲线拟合能够得到与经验公式相一致的体视学参数相关关系.结论 本文所述算法具有可行性,可以反映数值模拟结果的正确性.