Preclinical metabolism and disposition of [C]GFH009, a novel selective CDK9 inhibitor.

GFH009 is a potent and highly selective cyclin-dependent kinase 9 (CDK9) inhibitor currently under phase II clinical trials. In this study, we investigated the metabolism and disposition of GFH009 in Sprague-Dawley (SD) rats, as well as metabolism of CD-1 mouse, SD rat, beagle dog, cynomolgus monkey, and human.A radiolabelled study indicated that [C]GFH009 was quickly and widely distributed throughout the body, but presented low levels in brain, testis, and epididymis after a single intravenous dose of 6 mg (100 µCi)/kg to SD rats.

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.

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.

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

We investigate the electronic properties and valley physics of Janus monolayer WSSe on a CrI 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.

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.

Asymmetric valley polarization and photoluminescence in MoS/MoO heterostructure.

We investigate circularly polarized photoluminescence (PL) in the MoS/MoO heterostructure, which was fabricated by transferring MoS monolayer to cover the MoO few layers on the SiO/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 MoS 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 MoS/MoO heterostructure.

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.

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.

[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.

[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).