Development and validation of a sensitive UPLC-MS/MS analytical method for GFH009 in rat plasma and its application to toxicokinetics studies.

GFH009 is a potent, highly selective, small molecule that targets and inhibits the activity of the CDK9/cyclin T1 regulatory complex of P-TEFb. This study aimed to develop and validate a highly selective and sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for precise quantification of GFH009 in rat plasma. This method was subsequently employed for conducting toxicokinetic studies of GFH009 in rats. Plasma was prepared using a simple protein precipitation method by acetonitrile. Chromatographic separation of the analytes was achieved on a BEH C18 analytical column with a rapid 3.0 min run time and a flow rate of 0.5 ml/min. The calibration curves for plasma samples exhibited excellent linearity over a wide concentration range of 1.0-1,000 ng/ml for GFH009. Intra- and inter-day accuracies were within 92.7-105.7%, and precisions were no more than 6.7%. Furthermore, the analyte demonstrated stability under four different storage conditions, with variations of <15.0%. This study pioneers a methodological innovation by introducing a highly reliable, specific and sensitive analytical method for GFH009 in rat plasma. The successful application of this method in toxicokinetic studies further underscores its significance, offering valuable insights for the methodology of clinical pharmacokinetic research.

Efficacy of Children Neuropsychological and Behavioral Scale in Screening for Autism Spectrum Disorders through a Combination of Developmental Surveillance.

OBJECTIVE: This study aimed to explore the clinical value of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) for Autism Spectrum Disorder (ASD) screening in the presence of developmental surveillance. METHODS: All participants were evaluated by the CNBS-R2016 and Gesell Developmental Schedules (GDS). Spearman's correlation coefficients and Kappa values were obtained. Taking GDS as a reference assessment, the performance of the CNBS-R2016 for detecting the developmental delays of children with ASD was analyzed with receiver operating characteristic (ROC) curves. The efficacy of the CNBS-R2016 to screen for ASD was explored by comparing Communication Warning Behavior with Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). RESULTS: In total, 150 children aged 12-42 months with ASD were enrolled. The developmental quotients of the CNBS-R2016 were correlated with those of the GDS (r=0.62-0.94). The CNBS-R2016 and GDS had good diagnostic agreement for developmental delays (Kappa=0.73-0.89), except for Fine Motor. There was a significant difference between the proportions of Fine Motor, delays detected by the CNBS-R2016 and GDS (86.0% vs. 77.3%). With GDS as a standard, the areas under the ROC curves of the CNBS-R2016 were above 0.95 for all the domains except Fine Motor, which was 0.70. In addition, the positive rate of ASD was 100.0% and 93.5% when the cut-off points of 7 and 12 in the Communication Warning Behavior subscale were used, respectively. CONCLUSION: The CNBS-R2016 performed well in developmental assessment and screening for children with ASD, especially by Communication Warning Behaviors subscale. Therefore, the CNBS-R2016 is worthy of clinical application in children with ASD in China.

Tunable valley polarization in Janus WSSe by magnetic proximity coupling to a CrI3 layer.

We investigate the electronic properties and valley physics of Janus monolayer WSSe on a CrI3 substrate layer based on first-principles calculations. It is shown that the K and K' valley degeneracy can be lifted which leads to valley polarization (VP) in the WSSe due to the magnetic proximity coupling to a magnetic substrate. The magnitude of VP is highly sensitive to the interfacial electronic properties and can be tuned by varying the stacking configurations of the heterostructure. Interestingly, the direction of VP can be altered by manipulating the layer alignment without reversing the magnetism orientation of the magnetic substrate CrI3. We suggest that the hybridization between the bands of WSSe and the substrate plays an important role. Meanwhile, the charge distributions have been mapped out to uncover the microscopic origin of the direction variable VP. In addition, large VP can be achieved by adjusting the interlayer spacing. Our investigations may have potential applications in the design of valleytronic devices.

Synthesis and in vitro and in vivo biological evaluation of novel derivatives of flexicaulin A as antiproliferative agents.

As our research focuses on anticancer drugs, a series of novel derivatives of flexicaulin A (FA), an ent-kaurene diterpene, condensed with an aromatic ring were synthesized, and their antiproliferative activities against four human cancer cell lines (TE-1, EC109, MCF-7, and MGC-803) were evaluated. The activities of most of the new compounds were better than those of FA. Compound 2y exhibited the best activity with an IC50 value reaching 0.13 µM against oesophageal cancer cells (EC109 cells). The IC50 values for 2y in normal cells (GES-1 cells and HUVECs) were 0.52 µM and 0.49 µM, respectively. Subsequent mechanistic investigations found that compound 2y can inhibit the proliferation of cancer cells and cell cloning. In addition, 2y could reduce the mitochondrial membrane potential, increase the apoptosis rate, and increase the ROS level in EC109 cells. Moreover, 2y can upregulate the expression of ROS/JNK pathway-related proteins (p-ASK1, p-MKK4, p-JNK, and p-Cjun (ser63)) and pro-apoptotic proteins (Bax, Bad, and Bim). In vivo experiments showed that 2y can inhibit tumour growth in nude mice. The mechanism involves an increase in protein expression in the ROS pathway, leading to changes in apoptosis-related proteins. In addition, compound 2y shows low toxicity. These results indicate that compound 2y holds promising potential as an antiproliferative agent.

Asymmetric valley polarization and photoluminescence in MoS2/MoO3 heterostructure.

We investigate circularly polarized photoluminescence (PL) in the MoS2/MoO3 heterostructure, which was fabricated by transferring MoS2 monolayer to cover the MoO3 few layers on the SiO2/Si substrate. It is shown that the PL with the same helicity as the excitation light is dominant due to the inherent chiral optical selectivity, which allows exciting one of the valleys in MoS2 monolayer. The degree of polarization (DP), which characterizes the intensity difference of two chiral components of PL, is unequal for the right-handed and left-handed circularly polarized excitations in the MoS2/MoO3 heterostructure. This effect is different from the one in pristine MoS2. Our Raman spectra results together with ab initio calculations indicate the p-doped features of the MoS2 when it covers the MoO3 layers. Thus the possible explanation of the unequal DP is that the p-doping process generates a built-in voltage and therefore brings the difference of electron-hole overlaps between K and K' valleys. Namely the asymmetric valley polarization may be obtained in the MoS2/MoO3 heterostructure. Consequently, the circularly polarized PL caused by the electron-hole recombination at K and K' valleys manifests unequal DP for the right-handed and left-handed helix excitations. This asymmetric effect is further enhanced by decreasing the temperature in the MoS2/MoO3 heterostructure. Our investigation provides a unique platform for developing novel two-dimensional valleytronic devices.

Vocational Status of Occupational Therapists in Five Countries / 中国康复理论与实践

After retrieving the databases, as well as the official websites of institutes and administrations of occupational therapists, the qualifications, working conditions and career development in different countries, such as the United States, Canada, Australia, New Zealand and England, were collected and analyzed, which may provide reference frame for the development of the profession in China.

The prediction of a family group of two-dimensional node-line semimetals.

Using first-principles calculations, we predict a family group of two-dimensional semimetals MX (M = Pd, Pt; X = S, Se, Te), which has a zig-zag type mono-layer structure in the Pmma (no. 41) layer group. Band structure analysis reveals that node-line features are caused by band inversion and the inversion exists even in the absence of spin-orbital-coupling. First-principles calculations show the robust lattice stability of these predicted materials. This work provides the possibility of making a group of novel two-dimensional materials with semimetal features.

Effect of beta-tricalcium phosphate/poly-l-lactide composites on radial bone defects of rabbit

OBJECTIVE@#To explore the effect ofβ-TCP/PLLA scaffold in repairing rabbit radial bone defects.@*METHODS@#Thirty New Zealand rabbits were divided into β-TCP /PLLA group (group A), pure PLLA group (group B) and contrast group (group C) randomly. The rabbits were sacrificed respectively after 4, 8, 12, 24 weeks and the X-ray film was performed at the same time to evaluate the repair effect in different groups.@*RESULTS@#X-ray film showed there was uneven low density bone callus development in defect region after 4 weeks in group A. The defect region was filled with neonate osseous tissue completely during 12-24 weeks. X-ray score revealed that repair of bone defect results significantly better than group B and group C.@*CONCLUSIONS@#The β-TCP /PLLA composite is capable of repairing radial bone bone defects. β-TCP/PLLA scaffold is significant because of rapid degradation ability, good histocompatibility and osteogenic action.

Watching outside while under a carpet cloak of invisibility.

We demonstrate in this work a unique approach for watching outside while hiding in a carpet cloaking based on transformation optics. Unlike conventional carpet cloaking, which screens all the incident electromagnetic waves, we break the cloak and allow incident light get into the carpet. Hence outside information is detected inside the cloak. To recover the invisible cloaking, complementary techniques are applied in the broken space. Consequently, a hiding-inside and watching-outside (HIWO) carpet cloak is sewed, which works as an invisible cloaking and allows surveillance of the outside at the same time. Our work provides a strategy for an ideal cloak with "hiding" and "watching" functions simultaneously.

[Comparison of reliability of bispectral index and sedation-agitation scale in assessing the depth of sedation in patients treated with mechanical ventilation].

OBJECTIVE: To compare the reliability of bispectral index (BIS) with sedation agitation scale (SAS) in assessing the depth of sedation in ill patients on mechanical ventilation in intensive care unit (ICU). METHODS: Fifteen patients, aged 18-65 years old, who were receiving mechanical ventilation in ICU for longer than 72 hours and without brain dysfunction, were enrolled in this study. Sedatives and analgesics were suspended at 7:00 am. When patients fully woke up, propofol was infused till BIS score reaching 45-60. This was maintained for 10 minutes, then propofol dosage was decreased 10 microg . kg(-1) . min(-1) for every 10 minutes till all the drug was stopped. BIS was consecutively monitored and SAS was assessed in each interval. RESULTS: BIS score was markedly correlated with SAS (r=-0.6494, P<0.01). Although a significant correlation was still shown (r=-0.4566, P<0.01), there was wide variability in BIS scores when SAS reached 2-4. With decreasing of the propofol dosage, BIS score gradually increased. There was a satisfactory negative correlation between BIS scores and propofol dosage (r=-0.8076, P<0.01). SAS increased also following the decrease in propofol dosage, and a significant negative correlation was shown between SAS and the dosage of propofol (r=-0.6551, P<0.01). CONCLUSION: SAS is well correlated with BIS in assessing the depth of sedation in patients treated with mechanical ventilation in ICU. BIS is an objective, efficient tool for monitoring the depth of sedation in ICU critical patients who are receiving mechanical ventilation, and it is more reliable than SAS, especially when sedated levels reaching SAS 2-4.

[Study on safety of apnea test in clinical determination of brain death].

OBJECTIVE: To determine the occurrence of severe complications such as hypotension, pulmonary artery hypertension as well as hypercapnia during apnea test in the affirmation of brain death and to investigate the possible effective prophylactic interventions. METHODS: Conventional apnea test was performed in 15 clinically suspected brain death patients. Stable circulation was achieved by adjusting preload only (n=4) or combined with titrating norepinephrine (NE, n=11). Blood gas was respectively analyzed before apnea test, 10 minutes after 100% fraction of oxygen (FiO(2)) ventilation, at each 2-minute interval after disconnecting ventilator and 5 minutes after reventilation. Hemodynamic parameters and dosage of NE were recorded at the same time points. Plasma concentration of lactate was measured before and at the end of apnea test. RESULTS: Spontaneous breath occurred in 1 case among 15 suspected brain death patients. Partial pressure of carbon dioxide (PaCO(2)) reached higher than 60 mm Hg (1 mm Hg=0.133 kPa) within 8 minutes in positive apnea test patients (P<0.01). pH significantly decreased (P<0.05), but partial pressure of oxygen (PaO(2)) maintained higher than 100 mm Hg during the test. Heart rate (HR) and mean artery pressure (MAP) slightly lowered (P>0.05), but pulmonary artery pressure (PAP) markedly elevated (P<0.05) at the end of the test in comparison with their base lines. On the other hand, HR and MAP increased in the negative apnea test case after ventilator disconnection. Severe arrhythmia events did not occur in all the cases. There was no change in the dosage of NE infusion, the range of which was 0.10-0.60 microg.kg(-1).min(-1) with the mean level of (0.23+/-0.17) microg.kg(-1).min(-1). The trend of HR, MAP, PAP and pulmonary arterial wedge pressure (PAWP) alterations was the same in patients no matter whether or not NE was used. HR, MAP and PAWP lowered, while PAP enhanced. Plasma lactate level was not significantly altered at the end of the test compared with the base line (from (1.41+/-0.05) mmol/L to (1.47+/-0.07) mmol/L). CONCLUSION: Adequate oxygenation could be maintained during conventional apnea test. The risk of inducing severe hypotension is low in non brain death patients. Based on adequate preload, low dose of NE infusion could prevent patients with high risk circulation instability from severe hypotension.