Design,synthesis and in vitro evaluation of a series thiazolidinediones analogs as PPAR modulators

A series of thiazolidinediones analogs, as PPAR modulators, were designed, synthesized and evaluated in vitro.

Selective partial salivary glands sparing during intensity-modulated radiation therapy for nasopharyngeal carcinoma

Objective This study evaluated the dosimetric consequences of selective partial salivary gland sparing during intensity-modulated radiotherapy(IMRT) for patients with nasopharyngeal carcinoma(NPC).Methods Ten patients with NPC were enrolled in the study.Two IMRT plans were produced for each patient:conventional(control) and partial salivary glands-sparing(treatment),with dose constraints to the entire parotid glands or partial salivary glands(including the parotid and submandibular glands,delineated with the adjacent distance of at least 0.5 cm between the glands and PTV,the planning target volume) in planning,respectively.Dosimetric parameters were compared between the two plans,including the V_(110%),V_(100%),V_(95%)(the volume covered by more than 110%,100%,or 95% of the prescribed dose),Dmin(the minimum dose) of PTV,homogeneity index(HI),conformity index(CI),and the mean dose and percentage of the volume receiving 30 Gy or more(V_(30)) for the parotid glands and submandibular glands.Results Treatment plans had significantly lower mean doses and V_(30) to both the entire parotid glands and partial parotid glands than those in control plans.The mean doses to the partial submandibular glands were also significantly lower in treatment plans than in control plans.The PTV coverage was comparable between the two plans,as indicated by V_(100%),V_(95%),Dmin,CI,and HI.The doses to critical structures,including brainstem and spinal cord,were slightly but not significantly higher in treatment plans than in control plans.Conclusion A selective partial salivary gland-sparing approach reduces the doses to parotid and submandibular glands during IMRT,which may decrease the risk of post-radiation xerostomia while not compromising target dose coverage in patients with NPC.

Fabrication of 32 Gb/s Electroabsorption Modulated Distributed Feedback Lasers by Selective Area Growth Technology

A 32 Gb/s monolithically integrated electroabsorption modulated laser is fabricated by selective area growth technology. The threshold current of the device is below 13mA. The output power exceeds 10mW at 0V bias when the injection current of the distributed feedback laser is 100mA at 25℃. The side mode suppression ratio is over 50 dB. A 32Gb/s eye diagram is measured with a 3.SVpp nonreturn-to-zero pseudorandom modulation signal at -2.3 V bias. A clearly opening eyediagram with a dynamic extinction ratio of 8.01 dB is obtained.

Effects of estrogen receptor modulators on cytoskeletal proteins in the central nervous system

Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（NF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.

Design, Synthesis and Biological Evaluation of 2-Aroyl-3-aryl-6,7-dihydro-5H-furo[3,2-g]chromen Derivatives as a Novel Series of Estrogen Receptor Modulators

Based on the principles of the bioisosterism, combination of the active substructures of selective estrogen receptor modulators which are currently therapeutic agents available for the prevention and treatment of various estrogen dependent diseases, and structural optimization, a novel series of 2-aroyl-3-aryl-6,7-dihydro-5H-furo[3,2-g]- chromen derivatives was designed as potent selective estrogen receptor modulators via molecular docking. The target compounds have been synthesized, and characterized by 1R, proton NMR, ESI-MS, elemental analysis and evaluated for their antitumor activity against human osteosarcoma U2OS-EGFP-4FI2G cell line. Some target compounds showed good inhibition effects on U2OS-EGFP-4F12G cell line and the preliminary structure-activity relationships were discussed.

Modulating the Selectivity of Photocatalytic CO_(2)Reduction in Barium Titanate by Introducing Oxygen Vacancies

Artifi cial photosynthetic reduction of CO_(2) into valuable chemicals is one of the most promising approaches to solve the energy crisis and decreasing atmospheric CO_(2) emissions.However,the poor selectivity accompanied by the low activity of photocatalysts limits the development of photocatalytic CO_(2) reduction.Herein,inspired by the use of oxygen vacancy engi-neering to promote the adsorption and activation of CO_(2) molecules,we introduced oxygen vacancies in the representative barium titanate(BaTiO 3)photocatalyst for photocatalytic CO_(2) reduction.We found that oxygen vacancies brought signifi cant diff erences in the CO_(2) photoreduction activity and selectivity of BaTiO 3.The intrinsic BaTiO 3 showed a low photocatalytic activity with the dominant product of CO,whereas BaTiO 3 with oxygen vacancies exhibited a tenfold improvement in photocatalytic activity,with a high selectivity of~90%to CH 4.We propose that the presence of oxygen vacancies promotes CO_(2) and H 2 O adsorption onto the BaTiO 3 surface and also improves the separation and transfer of photogenerated carriers,thereby boosting the photocatalytic CO_(2) reduction to CH 4.This work highlights the essential role of oxygen vacancies in tuning the selectivity of photocatalytic reduction of CO_(2) into valuable chemicals.

Identification of neuron selective androgen receptor inhibitors

AIM To identify neuron-selective androgen receptor(AR) signaling inhibitors, which could be useful in the treatment of spinal and bulbar muscular atrophy(SBMA), or Kennedy's disease, a neuromuscular disorder in which deterioration of motor neurons leads to progressive muscle weakness. METHODS Cell lines representing prostate, kidney, neuron, adipose, and muscle tissue were developed that stably expressed the CFP-AR-YFP FRET reporter. We used these cells to screen a library of small molecules for cell typeselective AR inhibitors. Secondary screening in luciferase assays was used to identify the best cell-type specific AR inhibitors. The mechanism of action of a neuronselective AR inhibitor was examined in vitro using luciferase reporter assays, immunofluorescence microscopy, and immunoprecipitations. Rats were treated with the most potent compound and tissue-selective AR inhibition was examined using RT-q PCR of AR-regulated genes and immunohistochemistry.RESULTS We identified the thiazole class of antibiotics as com-pounds able to inhibit AR signaling in a neuronal cell line but not a muscle cell line. One of these antibiotics, thiostrepton is able to inhibit the activity of both wild type and polyglutamine expanded AR in neuronal GT1-7 cells with nanomolar potency. The thiazole antibiotics are known to inhibit FOXM1 activity and accordingly, a novel FOXM1 inhibitor FDI-6 also inhibited AR activity in a neuron-selective fashion. The selective inhibition of AR is likely indirect as the varied structures of these compounds would not suggest that they are competitive antagonists. Indeed, we found that FOXM1 expression correlates with cell-type selectivity, FOXM1 co-localizes with AR in the nucleus, and that sh RNA-mediated knock down of FOXM1 reduces AR activity and thiostrepton sensitivity in a neuronal cell line. Thiostrepton treatment reduces FOXM1 levels and the nuclear localization of beta-catenin, a known co-activator of both FOXM1 and AR, and reduces the association between beta-catenin and AR. Treatment of rats with thiostrepton demonstrated AR signaling inhibition in neurons, but not muscles. CONCLUSION Our results suggest that thiazole antibiotics, or other inhibitors of the AR-FOXM1 axis, can inhibit AR signaling selectively in motor neurons and may be useful in the treatment or prevention of SBMA symptoms.

Study on Module Selection Method for Customized Products

Modularization is the key technique for modern manufacturing system, which resolves the conflict between flexibility and productivity. The challenge of deciding which modules should choose under resource limitation from a large amount of available alternative modules has been well recognized in academia and industry correspondingly in producing customized production. For this reason, this paper proposes a new module selection method to deal with the problem, which combines rough set theory into total quality development (QFD) framework. First of all, a decision table is build up and then be modified through examining the importance of each attribute. Afterwards, the basic importance rating vector is calculated and the modifying index of the importance will be determined to get the final result. Finally, the feasibility and efficiency of the proposed method is manifested by a case study.

Pre-and post-selected measurements with coupling-strength-dependent modulation

Pre-and post-selected(PPS) measurement, especially the weak PPS measurement, has been proved to be a useful tool for measuring extremely tiny physical parameters. However, it is difficult to retain both the attainable highest measurement sensitivity and precision with the increase of the parameter to be measured. Here, a modulated PPS measurement scheme based on coupling-strength-dependent modulation is presented with the highest sensitivity and precision retained for an arbitrary coupling strength. This idea is demonstrated by comparing the modulated PPS measurement scheme with the standard PPS measurement scheme in the case of unbalanced input meter. By using the Fisher information metric, we derive the optimal pre-and post-selected states, as well as the optimal coupling-strength-dependent modulation without any restriction on the coupling strength. We also give the specific strategy of performing the modulated PPS measurement scheme, which may promote practical application of this scheme in precision metrology.

复杂场景下一种改进的单目标跟踪算法研究

针对部分复杂场景下目标跟踪存在跟踪框漂移问题,基于孪生候选区域生成网络(SiamRPN),融合通道注意力模块和选择核心模块(SK Module),提出一种单目标跟踪算法CAKSiamRPN。特征提取部分引入高效通道注意模块(ECAM)和基于标准化的通道注意力模块(NCAM),在不降低通道维度的情况下,摒弃相似信息,突出显著特征,关注并提取特定信息;在候选区域生成网络(RPN)嵌入SK Module,增强全局信息嵌入,减少填充操作的影响。将改进算法与SiamRPN及其它经典单目标跟踪算法在OTB100和UAV123数据集上进行实验对比。实验结果表明:跟踪精度和成功率明显提高,能更好地适应复杂场景,具有更强的鲁棒性。

面向带宽受限场景的高效语义通信方法

语义通信为通信系统优化和性能提升提供了新的研究角度,然而,目前语义通信的研究忽略了通信开销的影响,未考虑语义通信性能和通信开销的关系,导致带宽资源受限时语义通信性能难以提升。为此,针对带宽受限场景,提出一种基于信息瓶颈的语义通信方法。首先,该方法采用Transformer模型进行语义和信道联合编解码,并设计特征选择模块以识别和删除冗余语义信息,构建了端到端语义通信模型;进而考虑语义通信性能与通信开销之间的折衷关系,基于信息瓶颈理论设计损失函数,在保证语义通信性能的同时,降低通信开销,完成语义通信模型的训练和优化。实验结果显示,在欧洲议会平行语料库上,与基线模型相比,所提方法在保证通信性能的同时可降低约20%~30%的通信开销,在相同带宽条件下该方法的BLEU分数可提升约5%。实验结果表明,所提方法可以有效降低语义通信开销,从而提升带宽资源受限场景下的语义通信性能。

结合视角矫正和改进ViViT的驾驶员睡意判断方法

针对传统检测方法中摄像头视角受限问题,提出了一种结合面部姿态矫正和改进ViViT的多视角下人脸疲倦检测方法。采用Mediapipe Face Mesh定位面部三维特征点并将其矫正为正面,利用提出的FGR-ViViT模型来捕捉矫正后的眼睛、眉毛、嘴巴线条图像帧序列变化。FGR-ViViT通过在ViViT的Temporal Transformer Encoder中添加部件选择模块来捕捉特征在时间维度中的细微差异,同时融合2次dropout和改进的对比损失函数来调整样本的相似性,降低模型过拟合风险并提高泛化能力。实验结果表明,提出的方法在YawDD和DROZY矫正后的线条图像帧的测试集上,F1-分数达到了94.5%和97.6%,相较于原始人脸图像帧分别提高了3.2%和10.4%,其FGR-ViViT相较于原始ViViT分别提高了6.1%和0.7%。所提方法适用于摄像头灵活摆放的多种应用场景,对解决多视角人脸睡意判断具有积极意义。

改进蛇算法的七电平逆变器SHEPWM研究

多电平逆变器控制策略中的特定谐波消除脉宽调制(SHEPWM)能够以较低的开关频率得到较好的电压输出波形,重点在于开关角的求取。在多电平逆变器SHEPWM调制的开关角求解算法上提出改进蛇优化算法,对传统蛇优化算法采用Tend混沌映射初始种群,使初始种群分布更加均匀;引入Levy飞行策略增强算法的全局搜素能力,能够更加精准快速得到全局开关角的最优解。仿真结果表明,改进蛇优化算法所求的开关角相较于传统算法更好地消除低次谐波,并降低了输出线电压的畸变率,充分验证了该方法的可行性。

外用糖皮质激素引起的皮肤萎缩及其防治研究进展

皮肤萎缩是外用糖皮质激素最常见的副作用之一。外用糖皮质激素引起皮肤萎缩的机制包括:抑制角质形成细胞增殖、加快其分化成熟、抑制表皮脂质合成、抑制成纤维细胞增殖,减少胶原蛋白和透明质酸钠等细胞外基质合成等。近年来,对其副作用的防治主要集中在研发糖皮质激素受体的选择性调节剂、靶向抑制促萎缩基因及相关的信号通路、联合使用其他核受体的激动剂等方面,本文就其研究进展综述如下。

选择性PPARγ调节剂治疗糖尿病的研究新进展

过氧化物酶体增殖物激活受体γ是一类主要调控糖脂代谢与脂肪细胞分化的核受体,与肥胖、胰岛素抵抗和糖尿病的发生发展密切相关,其激动剂作为胰岛素增敏剂治疗2型糖尿病也被临床广泛应用。近年来,随着对PPARγ信号通路和胰岛素增敏剂的深入研究,使我们对选择性PPARγ调节剂类胰岛素增敏剂的认识不断完善和更新。该文主要阐述选择性PPARγ调节剂类胰岛素增敏剂的作用机制和药物研究的最新进展。

他莫昔芬治疗包裹性腹膜硬化症的研究进展

包裹性腹膜硬化症(EPS)是长期腹膜透析患者的一种少见且严重的并发症,主要见于长期腹膜透析和有反复、严重腹膜透析相关性腹膜炎(PDAP)病史者。EPS早期诊断困难,预后差、病死率高,其发病机制仍未完全清楚,目前缺乏理想的预防和治疗方案。他莫昔芬是一种选择性雌激素受体调节剂,目前可应用于治疗乳腺癌、卵巢癌及某些以纤维化病变为特征的疾病。有研究表明他莫昔芬也可用于治疗EPS。该文对EPS及他莫昔芬治疗EPS的相关研究进展进行了系统综述。

选择性雄激素受体调节剂在男性骨质疏松中的作用及机制

老年男性骨质疏松及骨折还没有引起足够的重视。性激素在原发性骨质疏松症及骨折发生发展中起着重要作用。睾酮是维持男性骨骼和肌肉质量的必需激素,雄激素能够促进肌肉骨骼合成代谢并改善骨质疏松,然而临床上男性老年雄激素替代治疗所引起的心血管事件和前列腺癌等风险增加限制了其常规使用。选择性雄激素受体调节剂通过与雄激素受体结合在不同组织细胞内诱导特异性的信号通路以及与5-α还原酶和芳香酶的局部相互作用实现组织选择性,从而减少雄激素替代治疗的常见不良反应。选择性雄激素受体调节剂目前已在多个动物实验中被证实能够促进骨合成、改善骨质疏松,但是相关的临床研究较少。本文对选择性雄激素受体调节剂在骨质疏松中的研究及机制进行讨论。

选择性PPARγ调节剂(SPPARγMs)研究新进展

2型糖尿病是全球性的重大公共卫生问题,过氧化物酶体增殖物激活受体γ(PPARγ)是发展抗2型糖尿病药物最受关注的靶点之一。由于已上市的PPARγ完全激动剂存在安全性问题,以PPARγ为作用靶点的抗2型糖尿病药物研究重心已经转移到开发安全性更好的选择性PPARγ调控剂(SPPARγMs),并且已有多个候选化合物进入到临床开发阶段。

活性位点电子密度变化对光催化CO_(2)活化和选择转化的影响

光催化二氧化碳(CO_(2))还原制液体燃料和高值化学品技术不仅能充分利用可再生能源太阳光,实现化学储能;更重要的是,此技术以温室气体CO_(2)为原料,因此可以减缓全球温室效应,构造人工碳循环。然而,光催化CO_(2)还原制液体燃料和高值化学品反应过程中面临诸多挑战:(1)CO_(2)分子吸附和活化过程困难;(2)(高附加值)碳产物选择性低;(3)产物生成后易发生其他副反应导致催化剂失活或产物选择性下降。受到以上三个挑战的制约,目前的反应效率较低,难以满足工业化应用。由于光催化CO_(2)向高值化学品的转化过程为质子耦合光生电子参与的还原反应,因此活性位点的电子密度会显著影响以上挑战的解决。然而,光催化CO_(2)还原过程涉及众多基元步骤,每个基元步骤对于活性位点的电子密度要求并不清晰,这导致无法有针对性设计高效的催化剂来促进光催化CO_(2)分子的有效活化及高选择性转化。本文综述了近期活性位点的电子密度变化对于CO_(2)分子吸附和活化过程、碳产物选择性调控和产物脱附及过氧化的影响规律,并总结了调控活性位点上电子密度的方法,旨在对未来设计高效光催化剂提供参考和理论依据。