Synthesis and antidepressant effect of novel aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT1A/5-HT7.

A series of novel aralkyl piperazine and piperidine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the selective compound were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compound 19a exhibited high affinities for the 5-HT1A/5-HT7 receptors (5-HT1A, Ki = 12 nM; 5-HT7, Ki = 3.2 nM) coupled with potent serotonin reuptake inhibition (IC50 = 14 nM) and showed a marked antidepressant-like effect in the FST and TST models.

Primary small cell carcinoma of the gallbladder diagnosed by PET/CT combined with tumour markers: A case report.

Small cell cancer (SCC) of the gallbladder is a rare and highly aggressive malignancy. We report here a case diagnosed by positron emission tomography/computed tomography (PET-CT) combined with tumour markers. A 51-year-old man presented with pain in his neck, shoulder, back, lumbar and right thigh. Ultrasonography showed an isoechoic mass in the gallbladder, and a magnetic resonance image (MRI) scan showed multiple retroperitoneal occupations and multiple vertebral bone destruction with pathological fractures. Blood analysis showed elevated levels of tumour markers including neuron-specific enolase (NSE) and PET/CT images showed extensive distant metastases. A diagnosis of primary SCC of the gallbladder was made following exclusion of the possibility of metastasis from other organs. The use of biomarkers with immunohistochemical findings and PET/CT imaging, will assist clinicians in the identification and understanding of the pathology of this disease.

Localized States and resultant band bending in graphene antidot superlattices.

We fabricated dye sensitized graphene antidot superlattices with the purpose of elucidating the role of the localized edge state density. The fluorescence from deposited dye molecules was found to strongly quench as a function of increasing antidot filling fraction, whereas it was enhanced in unpatterned but electrically backgated samples. This contrasting behavior is strongly indicative of a built-in lateral electric field that accounts for fluorescence quenching as well as p-type doping. These findings are of great interest for light-harvesting applications that require field separation of electron-hole pairs.

Value of transcranial color-code Doppler in evaluating intracranial atherosclerotic stenosis in patients with diabetes mellitus type 2: a comparison of transcranial Doppler and computed tomography angiography.

BACKGROUND: There are several imaging assessment methods for intracranial atherosclerotic stenosis (ICAS). This study investigated the most efficient method by which to diagnose ICAS in patients with diabetes mellitus. METHODS: One hundred seven patients with type 2 diabetes mellitus were enrolled as the experimental group and 68 healthy subjects were designated as the control group. The experimental group was examined with transcranial color-code Doppler (TCCD) and transcranial Doppler (TCD). Sixty-five patients in the experimental group were diagnosed by computed tomography angiography (CTA) on a voluntary basis. The 68 subjects in the control group were examined by TCCD alone. RESULTS: Based on TCCD examinations, the ICAS positivity rate was 71.0% (76/107) in the experimental group, which was greater than the 42.6% (29/68) in the control group (χ2=13.954, P<0.001). The middle cerebral artery was most frequently affected by ICAS (χ2=4.684, P=0.030), with a higher incidence of moderate and severe stenosis (χ2=4.510, P=0.034). The ICAS positivity rate was 64.6% (42/65) by TCCD, 75.4% (49/65) by CTA, and 53.8% (35/30) by TCD. There was a statistically significant difference between the TCCD and CTA (χ2=1.795, P=0.180) and between the TCD and CTA (χ2=6.594, P=0.010) positivity rates. CONCLUSIONS: ICAS is expected to occur in patients with diabetes mellitus more often than healthy subjects, and to involve the middle cerebral artery with moderate-to-severe stenosis. The ICAS positivity rate evaluated by TCCD was lower than CTA and higher than TCD.

Synthesis and antidepressant-like activity of novel aralkyl piperazine derivatives targeting SSRI/5-HT1A/5-HT7.

A series of novel aralkyl piperazine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the compounds were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compounds 21k (RUI, IC50 = 31 nM; 5-HT1A, 5-HT7, ki = 62, 12 nM) and 21n (RUI, IC50 = 25 nM; 5-HT1A, 5-HT7, ki = 28, 3.3 nM) exhibited high affinities for the 5-HT1A/5-HT7 receptors coupled with potent serotonin reuptake inhibition. Specifically, the most promising compound 21n possessed a good oral pharmacokinetic properties and an acceptable hERG profile, and showed potent antidepressant-like effect in the FST and TST models.

Analysis of metabolites of rocuronium bromide in human bile and the study of transmembrane transport mechanism / 药学学报

Rocuronium bromide is an acetylcholine N2 receptor antagonist, which can be used as an auxiliary drug for general anesthesia. It has been reported that rocuronium has two possible metabolic pathways: N-dealkylation and O-deacetylation, which are mainly taken up by liver and excreted by bile in the form of primary drugs. In this paper, the metabolites of rocuronium in human bile were detected by UHPLC-QE-orbitrap-MS, thirteen metabolites were detected, including eleven phase I metabolites and two phase II metabolites, eleven of which had not been previously reported. At the same time, HEK293 cells overexpressing transporter were used to explore the transmembrane transport mechanism of rocuronium, the results showed that rocuronium was the substrate of MATE1, OCT1, OATP1B1 and OATP1B3. The above research results enrich the metabolic pathway of rocuronium in vivo, and put forward the possible transport mechanism of liver uptake and bile excretion, which can better guide the accurate and safe clinical drug application. The collection of human bile samples in this study was approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Approval Number: 2019-775-130-01).

Suppression of blinking and enhanced exciton emission from individual carbon nanotubes.

Blinking and spectral diffusion are hallmarks of nanoscale light emitters and a challenge for creating stable fluorescent biomarkers or efficient nonclassical light sources. Here, we demonstrate suppression of blinking and spectral diffusion of individual single-wall carbon nanotubes by manipulation of their dielectric environment, resulting in 5-fold enhanced light emission. In addition, it was found that the characteristic slopes of the blinking power laws are largely independent of the dielectric environment in the limit of a large number of switching events. In contrast, the on/off ratio determined from statistical occurrence analysis is found to be improved by 3 orders of magnitude toward the on state, making the on/off ratio an important measure for charge transfer from/into the local dielectric environment of a quantum emitter. Furthermore, our approach is compatible with integration into cavities, in contrast to previous demonstrations of spectral diffusion suppression achieved in free-standing single-wall carbon nanotubes. This opens up possibilities to couple the exciton emission of nonblinking carbon nanotubes to cavity modes to further benefit by the Purcell effect and to enhance the light extraction efficiency, in order to ultimately demonstrate efficient photonic devices.

[Wavelet analysis on SO2 pollution index changes of Shanghai in recent 10 years].

Based on the continuous Mexican Hat wavelet transformation of time series of daily SO2 pollution index during last 10 years in Shanghai, the multiscale variations, primary period, catastrophe point and influencing factors are analyzed. The result shows that periodical fluctuation of SO2 pollution index varies at diverse time-scales, and the primary period of the daily variations is about 100 days; pollution pattern takes on serious in winter and light in summer in most scales due to meteorological conditions, and the catastrophe point of serious-light transformation of SO2 pollution index in a year is vernal and autumnal equinox; energy demand and socioeconomic development result in more seriousness in recent years and half result with twice the effort of endeavors of pollution elimination. Wavelet analysis is an effective method to time series of SO2 pollution index, also to multiscale variations of other pollutants.