摘要：A series of 2-arylamino-1,3,5-triazine derivatives(4a–4g),which were designed and synthesized via Sonogashira coupling reaction,were evaluated using two-electrode voltage clamp(TEVC)recordings of humanα7 nAChR expressed in Xenopus *** 4g as a positive allosteric modulator(PAM)showed better efficacy than lead compound 3(HZZ-A-11)with an EC50 value of 1.23±0.41μ*** pharmacological evaluation of compound 4g might lead to the developmental potential for therapy of cognitive deficits commonly shared by neuropsychiatric disorders,such as schizophrenia and Alzheimer’s disease.

摘要：Objectives The aim of this study was to analyze the psychometric properties(reliability and validity)of the Social Isolation Scale(SIS)in a sample of Portuguese community-dwelling older *** A transversal descriptive study was carried out with a convenience sample of 250 community-dwelling older adults(≥65 years).The survey comprised a sociodemographic questionnaire,SIS,Geriatric Depression Scale-4(GDS-4),6-item Lubben Social Network Scale(LSNS-6),a loneliness self-assessment question,and Satisfaction with Life Scale(SWLS).Construct validity(confirmatory factor analysis)and convergent validity were analyzed,and ISI internal reliability(composite reliability),external reliability(test-retest,intraclass correlation coefficient)and inter-rater reliability(Cohen’s kappa coefficient)were *** Confirmatory factor analysis showed a two-factor model with an excellent index of *** SIS showed significant correlations with LSNS-6(rs=0.47),SWLS(rs=0.26),the loneliness self-assessment question(rs=0.35),and GDS-4(rs=−0.16).SIS composite reliability was good(0.708).The inter-class correlation coefficient varied from 0.84 to *** Cohen’s kappa coefficient ranged from 0.936 to *** SIS has been shown to be a valid and reliable instrument for assessing social isolation among Portuguese community-dwelling older *** professionals,particularly nurses working in community settings,can use SIS to assess social isolation in older adults to design,implement,and evaluate interventions.

摘要：In this work the authors first summarily describe the main topics that were the subject of their post-graduate activity in fiber sensing at the Applied Optics Group of University of Kent in the late 1980s and early 1990s. After their return to Porto, Portugal, the know-how acquired during their stay at Kent and the collaboration paths that followed between the University of Porto and University of Kent were instrumental in the start-up and progress of optical fiber sensing activity in Portugal. The main topics addressed in this field, the description of some of the relevant developments achieved in recent years, the present situation and the guidelines for the future research and development activity in Portugal in fiber sensing will be the core of this work.

摘要：Objective To evaluate the accuracy of a three-dimensional (3D) magnetic position sensor system in the quantification of ventricular stroke volumes in a dynamic *** A latex balloon model of the left ventricle was suspended in a water bath connected to a pump producing 10 different pulsatile stroke volumes (15-65mi/beat). Scanning was performed using a 5.0 mHz transducer mounted with a Flock of Birds (FOB) magnetic receiver (GE System Five). The probe was scanned to sweep continuously across and over the balloon volume over 3 - 7 seconds. Digital loops were stored on magneto-optical disks and reviewed retrospectively using 3D Echopac software (GE)based on Simpson's method and compared with a two-dimensional (2D) biplane area-length method (1/2L x R) measurements at end systole and end diastole. Both 3D and 2D derived stroke volumes were compared with the reference stroke volume calculated by direct measurement of balloon *** There was an improved correlation between 3D stroke volume and reference stroke volume ( y = 0.91 x + 0.41, r = 0.97, SEE = 2.83 ml, P = 0.0001 ) compared to 2D stroke volume and reference stroke volume (y=0.49x+8.68, r=0.87, SEE=3.87 ml, P=0.0011, difference between 2D and 3D P＜0.003).Conclusion 3D magnetic FOB scanning is practical, accurate and should facilitate assessment of left ventricular function.

摘要：目的设计多感官型分心装置（MMD），观察其在烧伤换药和其他医疗过程中减轻患儿焦虑和疼痛的效果。方法设计3项前瞻性、随机对照临床试验。选择澳大利亚布里斯班皇家儿童医院烧伤中心和骨折整形外科患儿182例，共计354个医疗过程，分别应用标准分心法、手握电子游戏机和MMD（前MMD—D型、MMD-D型及MMD-PP型）。采用改良面部表情评分法、面部疼痛评分法、视觉模拟评分法及Wong，Baker面部表情疼痛评分法，记录患儿报告的疼痛分数、父母和护理人员报告的患儿焦虑和疼痛分数以及换药时间。结果与标准分心法组和电子游戏机组[（3．60±O．25）、（3．83±1．49）分]比较，MMD—D组与MMD—PP组患儿首次换药时的疼痛分数[（2．13±0．23）、（2．15±0．17）分]显著降低（P〈0．01），换药时间明显缩短（P〈0．01），且MMD在连续3次换药过程中均能发挥缓解疼痛的作用。此外，MMD-PP组患儿在换药前由焦虑引起的疼痛分数也较其他组显著降低（P〈0．01）。结论MMD较标准分心法和手握电子游戏机更能有效减轻患儿伤口处理过程中的焦虑和疼痛。该装置仍在临床试验中，且继续显示其有效性。

摘要：To overcome the main barrier of intestinal epithelium for the oral absorption of poorly water-soluble drugs and further improve their oral absorption, Gly-Sar, the substrate of the oligopeptide transporter PepT1 widely distributed in the small intestine,conjugated poly(ethylene glycol)-block-poly(D,L-lactide)(Gly-Sar-PEG-b-PLA) was designed and synthesized, and Pep T1-targeted polymeric micelles were prepared and characterized. The structure of the synthesized Gly-Sar-PEG-b-PLA was confirmed by use of TLC and 1 H-NMR. The average molecular weight measured by GPC was 5954 g/mol with PDI of 1.34. The DiI-loaded polymeric micelles from Gly-Sar-PEG-b-PLA with drug loading content of 0.076% were characterized to exhibit 40.36 nm in diameter with PDI of 0.294, and well-defined spherical shape observed by TEM. Furthermore, the PepT1-targeted polymeric micelles profoundly enhanced intestinal absorption of poorly water-soluble drug. Therefore, the designed PepT1-targeted polymeric micelles might have a promising potential for oral delivery of water-insoluble drugs.

摘要：In order to enhance the targeted delivery of anticancer drugs by polymeric micelles, folic acid(FA), the ligand of folate receptor(FR) over-expressed in the most cancer cells, modified p H-sensitive polymeric micelles were designed and fabricated to encapsulate doxorubicin(DOX) by combination of p H-sensitive amphiphilic polymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) with FA-conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide). The prepared micelles were characterized to have about 36 nm in diameter with narrow distribution, well-defined spherical shape observed under TEM and p H-responsive drug release behavior. Moreover, the tumor targeting ability of the FA-modified p H-sensitive polymeric micelles was demonstrated by the cellular uptake, in vitro cytotoxicity to FR-positive KB cells and in vivo real time near-infrared fluorescence imaging in KB tumor-bearing nude mice. The efficient drug delivery by the micelles was ascribed to the synergistic effects of FR-mediated targeting and p H-triggered drug release. In conclusion, the designed FR-targeted p H-sensitive polymeric micelles might be of great potential in tumor targeted delivery of water-insoluble anticancer drugs.

摘要：Oral administration is the best way for the most patients due to the good compliance,and intestinal epithelium is the main barrier of oral drug *** order to overcome the small intestine epithelial barrier to orally deliver water-insoluble drugs,deoxycholic acid(DA),a substrate of the intestinal bile acid transporters,conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)(DA-PEOz-PLA)was designed and synthesized,and deoxycholic acid-modified polymeric micelles composed of DA-PEOz-PLA and mPEG-PLA were fabricated to encapsulate model drug coumarin 6(C6)based on intestinal bile acid *** structure of DA-PEOz-PLA was confirmed using 1 H NMR and TLC,and the molecular weight measured by GPC was 10034 g/mol with a PDI of *** C6-loaded polymeric micelles with drug loading content of 0.085%were characterized to have 40.11 nm in diameter and uniform spherical morphology observed by ***,the deoxycholic acid-modified polymeric micelles were demonstrated to further enhance the transmembrane transport *** mechanic study evidenced that anchorage of deoxycholic acid onto the micelles surface enriched their transcellular transport ***,the designed deoxycholic acid-modified polymeric micelles might have a promising potential for oral delivery of water-insoluble drugs.

摘要：The intestinal epithelium is the main barrier to the oral delivery of poorly water-soluble drugs. Based on the specific transporters expressed on the apical membrane of the intestinal epithelium, novel polymer micelles targeting to the organic cation transporter 2（OCTN2） were constructed by combining carnitine conjugated poly（2-ethyl-2-oxazoline）-poly（D,L-lactide）（Car-PEOz-PLA） with monomethoxy poly（ethylene glycol）-poly（D,L-lactide）（mP EG-PLA）. The structure of the synthesized Car-PEOz-PLA was confirmed by -1H NMR, TLC and ammonium reineckate precipitation reaction, and the number-average molecular weight determined by GPC was 7260 g/mol with a low PDI of 1.44. Coumarin 6-loaded carnitine modified polymeric micelles prepared by film hydration method were characterized to have a nano-scaled size of about 31 nm in diameter, uniform spherical morphology, high drug loading content of 0.098%±0.03% and encapsulation efficiency of 92.67%±2.80%. Moreover, the carnitine-modified micelles exhibited the similar in vitro release behavior in SGF and SIF, and evidently enhanced intestinal absorption of poorly water-soluble agent. Therefore, the designed OCTN2-targeted micelles might have a promising potential for oral delivery of poorly water-soluble drugs.

摘要：The development of new proton-pump inhibitors (PPIs) with less adverse effects by lowering the pKa values of nitrogen atoms in pyrimidine rings has been previously suggested by our group. In this work, we proposed that new PPIs should have the following features:(1) number of ring II = number of ring I+ 1;(2) preferably five, six, or seven-membered heteroatomic ring for stability;and (3) 1<pKa1<4. Six molecular scaffolds based on the aforementioned criteria were constructed, and R groups were extracted from compounds in extensive data sources. A virtual molecule dataset was established, and the pKa values of specific atoms on the molecules in the dataset were calculated to select the molecules with required pKa values. Drug-likeness screening was further conducted to obtain the candidates that significantly reduced the adverse effects of long-term PPI use. This study provided insights and tools for designing targeted molecules in silico that are suitable for practical applications.