Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer.

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes.

Exploration of Novel -C═N-BODIPY-Based AIE Fluorescent Rotors with Large Stokes Shifts for Organelle-Viscosity Imaging.

The research on fluorescent rotors for viscosity has attracted extensive interest to better comprehend the close relationships of microviscosity variations with related diseases. Although scientists have made great efforts, fluorescent probes for cellular viscosity with both aggregation-induced emissions (AIEs) and large Stokes shifts to improve sensing properties have rarely been reported. Herein, we first report four new -C═N-substituted BODIPY-based rotors with large Stokes shifts, investigate their viscosity/AIE characteristics, and perform cellular imaging of the viscosity in subcellular organelles.

Meso-aryltellurium-BODIPY-based fluorescence turn-on probe for selective, sensitive and fast glutathione sensing in HepG2 cells.

Glutathione (GSH) as one most abundant thiol, acts as important roles in regulating cellular redox activities, and various diseases are closely related with its abnormal levels. Thus, monitoring intracellular GSH levels is essential for understanding cellular metabolism of many related diseases. In this work, we firstly reported a new fluorescence turn-on sensor, which was capable of selectively, sensitively and rapid sensing GSH over other thiols, especially cysteine and homocysteine in solutions and living cells.

Diagnostic performance of gadoxetic acid-enhanced abbreviated magnetic resonance imaging protocol in small hepatocellular carcinoma (≤2 cm) in high-risk patients.

Background: Biannual Ultrasound showed insufficient sensitivity in detecting small or early-stage hepatocellular carcinoma (HCC). Abbreviated magnetic resonance imaging (A-MRI) protocols with fewer sequences demonstrated higher HCC detection sensitivity than ultrasound with acceptable cost and examination time.

Purpose: To compare the diagnostic performance of gadoxetic acid-enhanced A-MRI with a full sequence MRI (F-MRI) protocol for small HCC (≤2 cm) in cirrhotic or hepatitis B virus-infected high-risk patients.

Deubiquitinase CYLD regulates excitatory synaptic transmission and short-term plasticity in the hippocampus.

The fate of proteins is determined by the addition of various forms of polyubiquitin during ubiquitin-mediated proteasomal degradation. Cylindromatosis (CYLD), a K63-specific deubiquitinase, is enriched in postsynaptic density fractions of the rodent central nervous system (CNS), but the synaptic role of CYLD in the CNS is poorly understand. Here we show that CYLD deficiency (Cyld) results in reduced intrinsic hippocampal neuronal firing, a decrease in the frequency of spontaneous excitatory postsynaptic currents and a decrease in the amplitude of field excitatory postsynaptic potentials.

Diagnostic Performance of Contrast Enhanced CT Alone or in Combination with (Non-)Enhanced MRI for Colorectal Liver Metastasis.

Rationale And Objectives: To compare the diagnostic performance of contrast enhanced CT (CE-CT), CE-CT combined with non-enhanced MRI (NE-MRI) or contrast enhanced MRI (CE-MRI) for colorectal liver metastasis (CRLM).

Materials And Methods: Sixty-six colorectal cancer patients with 198 focal liver lesions who underwent preoperative abdominal CE-CT and MRI examinations were included respectively. The images were assessed independently by two readers in three protocols (1: CE-CT, 2: CE-CT+NE-MRI, 3: CE-CT+CE-MRI).

Prognostic value of preoperative CT features for disease-free survival in patients with primary gastric gastrointestinal stromal tumors after resection.

Purpose: Tumor size is an important prognostic factor without consideration of the necrotic and cystic components within tumor for patients with gastrointestinal stromal tumors (GISTs). We aimed to extract the enhancing viable component from the tumor using computed tomography (CT) post-processing software and evaluate the value of preoperative CT features for predicting the disease-free survival (DFS) after curative resection for patients with primary gastric GISTs.

Methods: 132 Patients with primary gastric GISTs who underwent preoperative contrast-enhanced CT and curative resection were retrospectively analyzed.

Microvascular invasion of small hepatocellular carcinoma can be preoperatively predicted by the 3D quantification of MRI.

Objectives: To explore the importance of three-dimensional (3D) quantitative analysis during gadoxetic acid-enhanced magnetic resonance imaging (MRI) of microvascular invasion (MVI) and early recurrence (< 2 years) after surgery of single hepatocellular carcinoma (HCC) ≤ 3 cm.

Methods: Two hundred fourteen patients with pathologically confirmed HCC (training cohort: n = 169; validation cohort: n = 45) were included retrospectively. The 3D quantitative parameters (volume, sphericity, and compacity) and conventional MRI features were analyzed.

Blockade of TMEM16A protects against renal fibrosis by reducing intracellular Cl concentration.

Background And Purpose: Renal fibrosis is the final common outcome in most forms of chronic kidney disease (CKD). However, the underlying causal mechanisms remain obscure. The present study examined whether transmembrane member 16A (TMEM16A), a Ca -activated chloride channel, contributes to the progression of renal fibrosis.

Utility of preoperative computed tomography features in predicting the Ki-67 labeling index of gastric gastrointestinal stromal tumors.

Purpose: To evaluate the value of preoperative computed tomography (CT) features including morphologic and quantitative features for predicting the Ki-67 labeling index (Ki-67LI) of gastric gastrointestinal stromal tumors (GISTs).

Methods: We retrospectively included 167 patients with gastric GISTs who underwent preoperative contrast-enhanced CT. We assessed the morphologic features of preoperative CT images and the quantitative features including the maximum diameter of tumor, total tumor volume, mean total tumor CT value, necrosis volume, necrosis volume ratio, enhanced tissue volume, and mean CT value of enhanced tissue.

ClC-3 Deficiency Impairs the Neovascularization Capacity of Early Endothelial Progenitor Cells by Decreasing CXCR4/JAK-2 Signalling.

Background: Endothelial progenitor cell (EPC) therapy has been suggested as a major breakthrough in the treatment of ischemic diseases. However, the molecular mechanism that underlies EPC functional regulation is still unclear.

Methods: We examined the angiogenic capacity of EPCs in a hindlimb ischemia model of wild-type and ClC-3 knockout mice.

Hydrogen sulfide down-regulates BACE1 and PS1 via activating PI3K/Akt pathway in the brain of APP/PS1 transgenic mouse.

Background: Endogenous hydrogen sulfide (H2S) may have multiple physiological functions in brain. Our previous study showed that H2S improved spatial memory impairment and decreased the production of Aβ in APP/PS1 transgenic mice. However, many of the underlying mechanisms are not still being elucidated.

Upregulation of RBFOX1 in the malformed cortex of patients with intractable epilepsy and in cultured rat neurons.

Mutations in RNA‑binding Fox 1 (RBFOX1) are known to be associated with neurodevelopmental disorders including epilepsy, mental retardation and autism spectrum disorder. The deletion of the Rbfox1 gene in mice has been shown to result in heightened susceptibility to seizures. However, other studies have revealed mutations or the downregulation of RBFOX1 in specimens obtained from patients with epilepsy or malformations of cortical development (MCD).

[Clinical efficacy observation of acupuncture at suliao (GV 25) on improving regain of consciousness from coma in severe craniocerebral injury].

Objective: To compare the clinical therapeutic effects differences between acupuncture at Suliao (GV 25) and Shuigou (GV 26) on promoting regain of consciousness from coma in severe craniocerebral injury.

Methods: Based on regular emergency treatments of neurosurgery, eighty-two cases of craniocerebral injury who were under stable condition were randomly divided into an observation group (42 cases) and a control group (40 cases). Suliao (GV 25) was selected as main aupoint, while Laogong (PC 8) and Yongquan (KI 1), etc.

[Fluorescence spectroscopy study of human serum albumin quenched by rifampicin capsules].

It is obvious that the albumin is a kind of important large biophysical molecular. The albumin is the main component of plasma within cell. It is also the matter basis of life phenomenon.

[Fluorescence spectroscopy study of humen serum albumin quenched by levofloxacin].

The fluorescence spectroscopy of humen serum albumin (HSA) and the interaction of HSA and the Levofloxacin were studied. When the Levofloxacin was added into HSA solution gradually, an interesting new phenomenon emerged in emission spectrum peak. The intensity of 343.