Measurement of Hounsfield units on proximal femur computed tomography for predicting regional osteoporosis.

Objective: This study was designed to investigate the use of proximal femoral Hounsfield units (HU) in conventional abdominal and pelvic computed tomography (CT) to predict hip osteoporosis by coupling with data from quantitative CT (QCT).

Methods: In this study, 315 patients who underwent routine abdominal and pelvic CT with the proximal femur included in the scanning range were also subjected to QCT of the proximal femur. Pearson correlation test was performed to analyze the correlations of the femoral head, femoral neck, proximal femur, and femoral trochanter CT HU with the femoral neck, femoral trochanter, and intertrochanteric femur bone mineral density (BMD) values from QCT.

Pd(II)-Catalyzed Synthesis of Alicyclic[]-Fused Pyridines via C(sp)-H Activation of -Unsaturated -Acetyl Hydrazones with Vinyl Azides.

A new synthetic protocol for alicyclic[]-fused pyridines with complete regioselectivity from unsaturated -acetyl hydrazones and vinyl azides via Pd(II)-catalyzed C-H activation/cyclization/aromatization strategy has been described. A series of five- to eight-membered alicyclic[]-fused pyridines were prepared in a one-step manner with wide substrate scope and good functional group tolerance.

Detection of COVID-19 With CT Images Using Hybrid Complex Shearlet Scattering Networks.

With the ongoing worldwide coronavirus disease 2019 (COVID-19) pandemic, it is desirable to develop effective algorithms to automatically detect COVID-19 with chest computed tomography (CT) images. Recently, a considerable number of methods based on deep learning have indeed been proposed. However, training an accurate deep learning model requires a large-scale chest CT dataset, which is hard to collect due to the high contagiousness of COVID-19.

A novel Apigenin derivative suppresses renal cell carcinoma via directly inhibiting wild-type and mutant MET.

MET, the receptor of hepatocyte growth factor (HGF), is a driving factor in renal cell carcinoma (RCC) and also a proven drug target for cancer treatment. To improve the activity and to investigate the mechanisms of action of Apigenin (APG), novel derivatives of APG with improved properties were synthesized and their activities against Caki-1 human renal cancer cell line were evaluated. It was found that compound 15e exhibited excellent potency against the growth of multiple RCC cell lines including Caki-1, Caki-2 and ACHN and is superior to APG and Crizotinib.

Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis.

Emitasvir is a new type of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance. We conducted this phase 3 trial to further verify the efficacy and safety. We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate (100 mg) combined with sofosbuvir (400 mg) once daily in non-cirrhotic patients with genotype 1 HCV infection.

Development of DHQ-based chemical biology probe to profile cellular targets for HBV.

Chronic hepatitis B virus (HBV) infection has been a serious public health burden worldwide. Current anti-HBV therapies could not eliminate HBV ultimately. Considering the characteristics of HBV, it is impossible to be entirely cured based on current therapies.

Access to Cycloalkeno[]-Fused Pyridines via Pd-Catalyzed C(sp)-H Activation and Cyclization of -Acetyl Hydrazones of Acylcycloalkenes with Vinyl Azides.

A novel Pd(II)-catalyzed vinylic C-H activation and cyclization has been developed, reacting a series of small, medium, and large -acetyl hydrazones of acylcycloalkenes with vinyl azides to access diverse cycloalkeno[]-fused pyridine scaffolds. This protocol provides progress in C(sp)-H bond activation of medium to large cycloalkenes, and the target products can be obtained in a specific regioselectivity with good functional group tolerance and a broad substrate scope.

Radiomics Based on Lumbar Spine Magnetic Resonance Imaging to Detect Osteoporosis.

Rationale And Objectives: Signal intensity of the lumbar spine in magnetic resonance imaging (MRI) correlates to bone mineral density (BMD). This study aims to explore a lumbar spine magnetic resonance imaging based on the radiomics model for detecting osteoporosis.

Materials And Methods: A total of 109 patients, who underwent both dual-energy X-ray absorptiometry (DEXA) and MRI of the lumbar spine, were recruited.

Synthesis of 2,1-Benzoisoxazole-Containing 1,2,3-Triazoles through Copper-Catalyzed Three-Component Domino Reactions of -Bromoacetophenones, Aldehydes, and Sodium Azide.

We herein describe an efficient copper-catalyzed three-component domino protocol used to prepare 2,1-benzoisoxazole-containing 1,2,3-triazoles from commercially available -bromoacetophenones, aldehydes, and sodium azide. This domino process involves Aldol condensation, copper-catalyzed azide-chalcone oxidative cyclization, 1,2,3-triazole-assisted azidation, and denitrogenative cyclization sequences. The formed compounds could be considered as benzo[]isoxazole-functionalized combretastatin A-4 triazole analogues, which might be potential applications in the discovery of a new anticarcinogen.

A First-in-Human Trial of GLS4, a Novel Inhibitor of Hepatitis B Virus Capsid Assembly, following Single- and Multiple-Ascending-Oral-Dose Studies with or without Ritonavir in Healthy Adult Volunteers.

GLS4 is a novel inhibitor of the hepatitis B virus (HBV) capsid assembly with inhibitory activities against nucleot(s)ide-resistant HBV strains. This study investigated the pharmacokinetics, safety, and tolerability of GLS4 and the effects of food and ritonavir in healthy adults. GLS4 was administered in a single-ascending-dose study over 1 to 240 mg and multiple-ascending-dose study that ranged from 30 mg once daily to 180 mg three times daily.

Safety, Tolerability and Pharmacokinetics of Yimitasvir Phosphate Capsule, a Novel Oral Hepatitis C Virus NS5A Inhibitor, in Healthy Chinese Volunteers.

Background And Objectives: Yimitasvir is a novel oral hepatitis C virus non-structural protein 5A (NS5A) inhibitor. The aims of this first-in-human study were to evaluate the safety, tolerability and pharmacokinetics of single and multiple doses of yimitasvir in healthy adult Chinese volunteers and to assess the effect of food on yimitasvir pharmacokinetics.

Methods: Randomized, double-blind, placebo-controlled, single-ascending-dose (30, 100, 200 and 400 mg) and multiple-ascending-dose (100 and 200 mg once daily for 7 days) studies were performed in 32 and 24 subjects, respectively, in male and female adults.

3-((R)-4-(((R)-6-(2-Bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-2-(thiazol-2-yl)-3,6-dihydropyrimidin-4-yl)methyl)morpholin-2-yl)propanoic Acid (HEC72702), a Novel Hepatitis B Virus Capsid Inhibitor Based on Clinical Candidate GLS4.

The inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for the development of chronic hepatitis B (CHB) therapeutics. On the basis of the preclinical properties and clinical results of GLS4, we carried out further investigation to seek a better candidate compound with appropriate anti-HBV potency, reduced hERG activity, decreased CYP enzyme induction, and improved pharmacokinetic (PK) properties. To this end, we have successfully found that morpholine carboxyl analogues with comparable anti-HBV activities to that of GLS4 showed decreased hERG activities, but they displayed strong CYP3A4 induction in a concentration-dependent manner, except for morpholine propionic acid analogues.

Influences on viral replication and sensitivity to GLS4, a HAP compound, of naturally occurring T109/V124 mutations in hepatitis B virus core protein.

Heteroaryldihydropyrimidine (HAP) compounds inhibit HBV replication by binding to a hydrophobic pocket at the interface between hepatitis B virus core protein (HBcAg) dimer, which interrupts capsid assembly by changing the kinetics and thermodynamics during this process. Structure biological studies have identified several amino acids in HBcAg crucial for compound binding. Here, we investigated the polymorphisms of T109 and V124 amino acids in HBV sequences submitted to GenBank database.

Discovery of hepatitis B virus capsid assembly inhibitors leading to a heteroaryldihydropyrimidine based clinical candidate (GLS4).

Inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for the development of chronic hepatitis B (CHB) therapeutics. Herein we described our lead optimization studies including the synthesis, molecular docking studies and structure-activity relationship (SAR) studies of a series of novel heteroaryldihydropyrimidine (HAP) inhibitors of HBV capsid assembly inhibitors, and the discovery of a potent inhibitor of HBV capsid assembly of GLS4 (ethyl 4-[2-bromo-4-fluorophenyl]-6-[morpholino-methyl]-2-[2-thiazolyl]-1,4-dihydro-pyrimidine-5-carboxylate) which is now in clinical phase 2. GLS4 demonstrated potent inhibitory activities in HBV HepG2.

Preclinical characterization of GLS4, an inhibitor of hepatitis B virus core particle assembly.

Hepatitis B virus (HBV)-associated chronic liver diseases are treated with nucleoside analogs that target the virus polymerase. While these analogs are potent, drugs are needed to target other virus-encoded gene products to better block the virus replication cycle and chronic liver disease. This work further characterized GLS4 and compared it to the related BAY 41-4109, both of which trigger aberrant HBV core particle assembly, where the virus replication cycle occurs.

(1) H and (13) C NMR assignments of four series bioactive pyrido[4,3-d]pyrimidine derivatives.

The complete (1) H and (13) C NMR assignments of four series pyrido[4,3-d]pyrimidine derivatives were achieved by combination of one and two-dimensional NMR experiments, and the NMR signals of these compounds were analyzed and compared.

[The effect of the metallic dental materials on magnetic resonance imaging].

Objective: To explore the influence of conventional metal materials in oral cavity on brain magnetic resonance imaging (MRI).

Methods: Four kinds of metal materials (metal ligature wire, forging hard and slotless denture, casting nichrome denture, casting copper alloy denture) in oral cavity were scanned through MRI. FSE sequence T1 weighted imaging (FSE T1), EPI diffusion-weighted imaging (DWI) sequence of ordinary, Propeller DWI imaging were used.

A facile synthesis and biological activity of novel tetrahydrobenzo[4',5']thieno[3',2':5,6]pyrido[4,3-d]pyrimidin-4(3H)-ones.

The synthesis and biological activity of 2-substituted-8,9,10,11-tetrahydrobenzo[4',5']thieno[3',2':5,6] pyrido[4,3-d]pyrimidin-4(3H)-ones are described. Bioassay results indicated that these compounds have antifungal activity against Botrytis cinerea at a concentration of 50mg/L. In addition, compounds 5m and 5n were effective to both KB cells and their parent multidrug resistant KBv200 cells with the overexpression of ABCB1.

[The evaluation of virtual endoscopy and fiberoptic endoscopy in the diagnosis of obstructive sleep apnea syndrome].

Objective: The utility of virtual endoscopy is compared to fiberoptic endoscopy and was also investigated with respect to accuracy of diagnosis and reproduction of images in patients with obstructive sleep apnea hypopnea syndrome (OSAHS).

Method: Twenty-one patients with OSAHS were examined by helical spiral CT axial images and fiberoptic endoscopy. The helical spiral CT axial data was reconstructed using a VE software program.