Chiral Acetal-Based Stereo-Controlled Degradable Polymer Synthesis.

The precise synthesis of chiral polymers remains a significant challenge in polymer chemistry, particularly for applications in advanced biomedical and electronic materials. The development of degradable polymers is important for eco-friendly and advanced materials. Here, we introduce a stereo-controlled degradable polymer via cascade enyne metathesis polymerization and enantioselective acetal synthesis through Pd-catalyzed asymmetric hydroamination. This approach allows for the creation of chiral acetal-based polymers with controlled stereochemistry and degradability, highlighting their potential for use in drug delivery and electronic applications. This concept article reviews the background, development, and potential applications of these stereo-controlled degradable polymers.

The function of the glutathione peroxidase family and the possibility of its members as immunotherapeutic markers for glioma / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨谷胱甘肽过氧化物酶（GPX）家族在胶质瘤发生发展中的生物学功能和预后价值。方法：利用TCGA、GTEx和CGGA等多个数据库数据分析胶质瘤中GPX各亚型基因的表达及其相关性、蛋白之间的相互作用、基因突变、GPX表达与胶质瘤患者预后的关系以及GPX7、8的基因集富集分析；GPX8与胶质瘤中免疫细胞浸润以及免疫检查点分子表达的相关性分析，胶质瘤中GPX8表达与化疗药物IC50的相关性分析。采用qPCR法、WB法和免疫荧光技术检测国人胶质瘤组织和对照组织（标本收集自2022年10月20日至12月20日间在上海奉贤区中心医院神经外科手术切除的5例胶质瘤和3例严重脑外伤的病灶组织）中GPX mRNA、蛋白以及相关免疫检查点分子的表达进行验证。结果：数据库分析显示胶质瘤中GPX各亚型蛋白之间存在相互作用、基因表达水平存在相关性（P<0.05或P<0.01），胶质瘤组织中多个GPX亚型存在单核苷酸变异和拷贝数变异；不同类型胶质瘤组织的免疫细胞和肿瘤细胞中主要表达的GPX亚型有明显不同，在胶质瘤组织中GPX1、4、7、8均呈高表达（均P<0.05）且与胶质瘤患者预后不良相关（P<0.01）。qPCR法、WB法检测中国人胶质瘤组织中GPX7、8均呈高表达验证了数据库信息的正确性。在胶质瘤中GPX7、8表达具有独立预后预测价值；富集分析显示GPX7、8与胶质瘤细胞周期和免疫途径有关，在GBM和LGG中GPX8表达与免疫评分呈明显相关（P<0.01）、GPX8可能在胶质瘤中诱导抑制性免疫细胞浸润导致免疫抑制、GPX8表达与胶质瘤中多个免疫检查点分子表达正相关（均P<0.01）、GPX8表达与化疗药物IC50呈明显正相关（均P<0.01）且其高表达可导致胶质瘤对化疗药物的耐药。结论：GPX8在胶质瘤中呈显著高表达，GPX8高表达能诱导胶质瘤中抑制性免疫细胞的浸润其与多个免疫抑制点、与多个化疗药物IC50和患者预后密切相关，可作为胶质瘤免疫治疗的潜在靶点。

Regulating the Acidity of SO3 H-Functionalized Ionic Liquids: Hydrogen Bonding or Electrostatic Potential?

The SO3 H-functionalized ionic liquids (ILs) with high acidity are important catalysts for acid-catalyzed reactions. However, the acidity of these ILs have been found to decrease due to intramolecular hydrogen bonds (H-bonds). In this work, a series of anionic SO3 H-functionalized ILs were designed and the factors resulting in weak acidity were investigated, including H-bonds strength and electrostatic potential on the leaving proton (ESPLP). Using catalytic experiment, atoms in molecules topology analysis and electrostatic potential calculation, it was found that the acidity of ILs was correlated with the value of ESPLP rather than the H-bond strength. Meanwhile, there were several ways to increase the acidity of anionic SO3 H-functionalized ILs, such as enhancing the electron-withdrawing ability of cation, introducing H-bond acceptor sites on cation or separating the intramolecular H-bonds through substitution position. These strategies made the conversion of TBA in Friedel-Crafts alkylation increase from 19 % to 84 %.

Motion type and knee articular conformity influenced mid-flexion stability of a single radius knee prosthesis.

PURPOSE: Single radius knee implants were introduced to reduce the level of paradoxical anterior femoral translation (AFT) during mid-flexion after total knee arthroplasty. Findings from clinical and experiment studies are inconsistent, which may be due to the different loading conditions and articular conformities of the knee implants studied. The aim of this study is to analyze how variations in these two factors affect the mid-flexion stability of a single radius knee prosthesis. METHODS: Six daily activities (walking, stair ascent, stair descent, sit-to-stand, pivot turn and crossover turn), and three articular conformity ratios (low, moderate and high) were considered. The resulting AFTs from the 18 finite element models were analyzed. RESULTS: For low conformity knees, the worst case activity (the greatest AFT) was sit-to-stand with an AFT of 6.2 mm, while for the moderate conformity the worst case was crossover turn and pivot turn. For high conformity, all activities produced a relatively small AFT ranging from 0 mm to 1.8 mm, which more closely resembles natural knee motion. In addition, no AFT was recorded during stair ascent for all three conformities (low, moderate, high). CONCLUSIONS: This study demonstrated that the amount of AFT is highly dependent on the activity being undertaken and the articular conformity of the knee prosthesis, and the worst case activity depends on the knee conformity. The clinical relevance of this study is that it offers valuable information towards the design of improved knee prostheses and selection of knee implants for clinical use. LEVEL OF EVIDENCE: II.

The impact of variations in input directions according to ISO 14243 on wearing of knee prostheses.

ISO 14243 is the governing standard for wear testing of knee prostheses, but there is controversy over the correct direction of anterior-posterior (AP) displacement and loading and the correct direction of tibial rotation (TR) angles and torque. This study aimed to analyze how altering the direction of AP and TR affected wear on the tibial insert. Modifications to the conditions specified in ISO 14243-1 and ISO 14243-3 were also proposed. As such, five loading conditions were applied to FEA models of a knee prosthesis: (1) Modified ISO 14243-3 with positive AP displacement and TR angle, (2) ISO 14243-3:2004 with negative AP displacement and positive TR angle, (3) ISO 14243-3:2014 with positive AP displacement and negative TR angle, (4) Modified ISO 14243-1 with positive AP load and TR torque, and (5) ISO 14243-1:2009 with negative AP load and positive TR torque. This study found that changing the input directions for AP and TR according to ISO 14243-1 and 14243-3 had an influence on the wear rate and wear contours on the tibial insert model. However, the extent of wear varies depending on the design features of the tibial insert and shape of the input curves. For displacement control according to ISO 14243-3, changing the direction of AP displacement had a marked influence on the wear rate (272.77%), but changing the direction of TR angle had a much lower impact (2.17%). For load control according to ISO 14243-1, reversing the AP load (ISO 14243-1:2009) only increased the wear rate by 6.73% in comparison to the modified ISO 14243-1 conditions. The clinical relevance of this study is that the results demonstrate that tibial wear is affected by the direction of application of AP and TR. Incorrect application of the loading conditions during the design stage may lead to an ineffective preclinical evaluation and could subsequently influence implant longevity in clinical use.

[The myeloid cell leukemia-1 mRNA splicing mediated by epithelial splicing regulatory protein 1 (ESRP1) in glioma U251 cell lines].

OBJECTIVE: To investigate the regulatory mechanism of myeloid cell leukemia-1 (MCL1) mRNA splicing mediated by epithelial splicing regulatory protein 1 (ESRP1) in glioma U251 cell lines. METHODS: Data mining was performed in glioma patient database to find out the key sites from MCL1 sequencing results. Exogenous ESRP1 was over-expressed in U251 cells via pcDNA-ESRP1 vector. The levels of different MCL1 isoforms were detected by reverse transcription PCR and Western blotting. RESULTS: The mRNA and protein level of endogenous ESRP1 was lower in U251 cells than in normal gliocytes. The level of MCL1 isoform 1 was higher, while isoform 2 and 3 were lower in U251 cells than in normal gliocytes. Furthermore, MCL1 isoform 1 was reduced and isoform 3 was up-regulated in U251 cells after ESRP1 over-expression. Isoform 2 was unchanged obviously. Finally, MCL1 with the deletion of 801G and 802A sites could not be correctly spliced by ESRP1 and no significant difference was seen in the expressions of isoform 1 and 3 in mutant MCL1. CONCLUSION: Repression of ESRP1 expression or mutation in its RNA recognized sites in tumor results in the abnormality of transcript splicing of oncogenes.

Is the posterior cruciate ligament necessary for medial pivot knee prostheses with regard to postoperative kinematics?

PURPOSE: Excellent clinical and kinematical performance is commonly reported after medial pivot knee arthroplasty. However, there is conflicting evidence as to whether the posterior cruciate ligament should be retained. This study simulated how the posterior cruciate ligament, post-cam mechanism and medial tibial insert morphology may affect postoperative kinematics. METHODS: After the computational intact knee model was validated according to the motion of a normal knee, four TKA models were built based on a medial pivot prosthesis; PS type, modified PS type, CR type with PCL retained and CR type with PCL sacrificed. Anteroposterior translation and axial rotation of femoral condyles on the tibia during 0°-135° knee flexion were analyzed. RESULTS: There was no significant difference in kinematics between the intact knee model and reported data for a normal knee. In all TKA models, normal motion was almost fully restored, except for the CR type with PCL sacrificed. Sacrificing the PCL produced paradoxical anterior femoral translation and tibial external rotation during full flexion. CONCLUSION: Either the posterior cruciate ligament or post-cam mechanism is necessary for medial pivot prostheses to regain normal kinematics after total knee arthroplasty. The morphology of medial tibial insert was also shown to produce a small but noticeable effect on knee kinematics. LEVEL OF EVIDENCE: V.

Study of the mechanism of sonodynamic therapy in a rat glioma model.

PURPOSE: The study reported here examined the effect of hematoporphyrin monomethyl ether (HMME)-mediated sonodynamic therapy (SDT) on C6 gliomas implanted in rat brains. METHODS: Two weeks after inoculation, glioma development was evaluated by measuring tumor volume using a 1.5 T magnetic resonance imager. Rats that had a well-developed C6 glioma (usually when the tumor diameter reached 3-5 mm) were used to test SDT, ultrasound-alone, and HMME-alone treatments. Rats both administered and not administered intravenous HMME 10 µg/mL were insonated by a 1 MHz ultrasound at a dose of 0.5 W/cm(2). RESULTS: SDT treatment could effectively inhibit the expansion of intracranial gliomas in vivo. The treatment with ultrasound alone could inhibit glioma growth within 1 week; however, 1 week later, the tumor started growing again. In contrast, the effect of SDT could last at least 2 weeks. Injection of HMME alone had no effects on inhibiting glioma growth, suggesting the sonosensitizer HMME has no antitumor effect. Both SDT and ultrasound-alone treatment could extend the survival of rats implanted with a C6 glioma. Pathological and electron microscopic examinations suggested SDT and ultrasound-alone treatment could induce glioma necrosis by way of triggering glioma-cell apoptosis, which was confirmed by immunohistological examination with cytochrome-c and caspase-3 antibodies. Most importantly, we found that the sonosensitizer HMME could enhance the ultrasound-induced antitumor effect by selectively assisting ultrasound targeting of glioma angiogenesis inhibition. CONCLUSION: This study with a rat C6 glioma experimental model showed that SDT can potentially be useful in the treatment of deep-seated malignant gliomas.

In vitro study of haematoporphyrin monomethyl ether-mediated sonodynamic effects on C6 glioma cells.

OBJECTIVES: To study the cytotoxicity induced by haematoporphyrin monomethyl ether (HMME)-mediated sonodynamic therapy (SDT) on C6 glioma cells. METHODS: The potent photosensitizer HMME was used as the sensitizer. Rat C6 glioma cells were incubated with HMME (10 microg/mL) in the dark for 2 h and then subjected to ultrasound treatment at 1.0 MHz and 0.5 W/cm2 for 2 min. The growth inhibition rate at different time points after SDT was determined by MTT assay. The apoptotic rate and cell circle profiles were examined with flow cytometry. Fine structures were observed with transmission electron microscope (TEM). The sonodynamic effect on the glioma cells was also studied in the absence or presence of various reactive oxygen species (ROS) scavengers. RESULTS: The growth inhibition rate of C6 glioma cells after SDT significantly increased. SDT also increased the apoptosis and proliferation rate (APR). TEM examination showed the morphological features of apoptosis or necrosis. The addition of NaN(3) showed a strong protective effect again SDT. CONCLUSIONS: Our data indicated that SDT could kill C6 glioma cells in vitro and possibility through induction of apoptosis and necrosis. Singlet oxygen ((1)O2) may play an important role in SDT.