Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.     

来自世博会的收获

1970年代初开始的世博会给日本建筑界带来了无数创作的机会和合作的场所，笔者通过讲述亲身的经历，介绍其所参加的世博会中的项目，并且记录了由作品阐述的自身想法，由合作创造的全新灵感和由参与总结的难得收获。作者也提出了对2010年上海世博会的看法和建议。     

Main‐chain smectic liquid crystalline polymer exhibiting unusually high thermal conductivity in an isotropic composite

The thermal conductivity (TC) of an isotropic composite comprising of a main‐chain smectic liquid crystalline PB‐10 polyester and 50‐μm‐sized roughly spherical magnesium oxide (MgO) particles is investigated. The increase in the composite TC with higher MgO fractions is steeper than that expected by Bruggeman's theory for the TC of a polydomain PB‐10 polyester (0.52 W m^?1 K^?1). When the filler content is larger than 30 vol %, the composite TC approaches a value that can be explained only if the polyester functions as a matrix with 1.0 W m^?1 K^?1, which is five times as high as those of isotropic common polymers (0.2 W m^?1 K^?1). Such an unusually high TC for a polymer matrix is attributed to some polymer lamellae that lie parallel to the particle surface and are stacked toward neighboring particles, thus creating effective heat paths between the particles and a continuous thermal network in a composite. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014 , 131, 39896.     

A chemically amplified molecular glass resist with an ionic photoacid generator and a single protection group

A molecular glass resist with an ionic photoacid generator and a single protection group (MR‐1) has been developed. MR‐1 exhibited good thermal properties, such as a 5% weight loss temperature (T_d5%) of 167°C and a glass transition temperature (T_g) of 80°C. MR‐1 showed the good sensitivity of 80 μC/cm² and high contrast of 4.9 with e‐beam exposure (50 keV). A relatively high resolution of 50 nm and low Line‐Edge‐Roughness of 3.8 nm were obtained by e‐beam exposure (100 keV). © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39769.     

Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation

While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-release once-daily tacrolimus formulation (0.20 mg/kg) was administered to 50 Japanese renal transplant patients every 24 h. Stepwise multiple linear regression analysis for tacrolimus dosing was performed each week to determine the effect of patient clinical characteristics. The dose-adjusted trough concentration was approximately 70% higher for patients with the CYP3A5*3/*3 than patients with the CYP3A5*1 allele before the second pre-transplantation tacrolimus dose (0.97 (0.78–1.17) vs. 0.59 (0.45–0.87) ng/mL/mg; p < 0.001). The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively. The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery. Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information.     

Acetaminophen-Induced Rat Hepatotoxicity Based on M1/M2-Macrophage Polarization,in Possible Relation to Damage-Associated Molecular Patterns and Autophagy

Overdose of acetaminophen (APAP), an antipyretic drug, is an important cause of liver injury. However, the mechanism in the rat model remains undetermined. We analyzed APAP-induced hepatotoxicity using rats based on M1/M2-macrophage functions in relation to damage-associated molecular patterns (DAMPs) and autophagy. Liver samples from six-week-old rats injected with APAP (1000 mg/kg BW, ip, once) after 15 h fasting were collected at hour 10, and on days 1, 2, 3, and 5. Liver lesions consisting of coagulation necrosis and inflammation were seen in the affected centrilobular area on days 1 and 2, and then, recovered with reparative fibrosis by day 5. Liver exudative enzymes increased transiently on day 1. CD68⁺ M1-macrophages increased significantly on days 1 and 2 with increased mRNAs of M1-related cytokines such as IFN-γ and TNF-α, whereas CD163⁺ M2-macrophages appeared later on days 2 and 3. Macrophages reacting to MHC class II and Iba1 showed M1-type polarization, and CD204⁺ macrophages tended to be polarized toward M2-type. At hour 10, interestingly, HMGB1 (representative DAMPs) and its related signals, TLR-9 and MyD88, as well as LC3B⁺ autophagosomes began to increase. Collectively, the pathogenesis of rat APAP hepatotoxicity, which is the first, detailed report for a rat model, might be influenced by macrophage functions of M1 type for tissue injury/inflammation and M2-type for anti-inflammatory/fibrosis; particularly, M1-type may function in relation to DAMPs and autophagy. Understanding the interplayed mechanisms would provide new insight into hepato-pathogenesis and contribute to the possible development of therapeutic strategies.     

Evaluation of Two Sets of Sorghum Bagasse Samples as the Feedstock for Fermentable Sugar Recovery via the Calcium Capturing by Carbonation (CaCCO) Process

Abstract: Sorghum bagasse samples from two sets (n6 and bmr6; n18 and bmr18) of wild-type and corresponding “brown midrib” (bmr) mutant strains of sweet sorghum were evaluated as the feedstock for fermentable sugar recovery via the calcium capturing by carbonation (CaCCO) process, which involves Ca(OH)₂ pretreatment of bagasse with subsequent neutralization with CO₂ for enzymatic saccharification. Saccharification tests under various pretreatment conditions of the CaCCO process at different Ca(OH)₂ concentrations, temperatures or residence periods indicated that bmr strains are more sensitive to the pretreatment than their counterparts are. It is expected that variant bmr6 is more suitable for glucose recovery than its wild-type counterpart because of the higher glucan content and better glucose recovery with less severe pretreatment. Meanwhile, bmr18showed higher scores of glucose recovery than its counterpart did, only at low pretreatment severity, and did not yield higher sugar recovery under the more severe conditions. The trend was similar to that of xylose recovery data from the two bmr strains. The advantages of bmr strains were also proven by means of simultaneous saccharification and fermentation of CaCCO-pretreated bagasse samples by pentose-fermenting yeast strain Candida shehatae Cs 4R. The amounts needed for production of 1 L of ethanol from n6, bmr6, n18, and bmr18samples were estimated as 4.11, 3.46, 4.03, and 3.95 kg, respectively. The bmr strains seem to have excellent compatibility with the CaCCO process for ethanol production, and it is expected that integrated research from the feedstock to bioprocess may result in breakthroughs for commercialization.     

基于非线性流形学习的人脸面部运动估计

由于人脸面部运动变化分布在一个低维非线性流形中,基于线性假设的主动外观模型采用主成分分析算法描述人脸形状的变化必然带来额外的估计误差.为降低或消除这一误差,该文提出一种改进的局部线性嵌入算法构建人脸形状-纹理空间,并将其应用于主动外观模型中.实验结果表明,不仅对于面部形变不大的人脸形状,局部线性嵌入-主动外观模型拥有更...