1-(3-Chloro­benzo­yl)-3-(2,3-dimethyl­phen­yl)thio­urea

The title mol­ecule, C16H15ClN2OS, exists in the solid state in its thione form with typical thio­urea C—S and C—O bonds lengths, as well as shortened C—N bonds. An intra­molecular N—H⋯O hydrogen bond stabilizes the mol­ecular conformation and inter­molecular N—H⋯S hydrogen bonds link the mol­ecules into centrosymmetric dimers. The dihedral angle between the aromatic rings is 50.18 (5)°

1-(4-Chloro­benzo­yl)-3-(2,4,6-trichloro­phen­yl)thio­urea hemihydrate

The asymmetric unit of the title compound, C14H8Cl4N2OS·0.5H2O, contains two independent mol­ecules with different conformations with respect to the aromatic ring planes, and one water mol­ecule. The bond lengths and angles are typical of thio­urea compounds of this class. The mol­ecule exists in the solid state in its thione form with typical thio­urea C—S and C—O bonds lengths, as well as shortened C—N bonds. The dihedral angles between the two aromatic planes are 66.93 (8) and 60.44 (9)° in the two independent mol­ecules. An intra­molecular N—H⋯O hydrogen bond stabilizes the mol­ecular conformation and the crystal packing is characterized by N—H⋯O, O—H⋯S and O—H⋯Cl hydrogen bonds

1-(2,6-Dichlorobenzoyl)-3-(3-methoxyphenyl)thiourea

The two aromatic rings in the title compound, C15H12Cl2N2O2S, enclose a dihedral angle of 37.49 (6)°. The molecule exists in the solid state in its thione form with typical thiourea C-S and C-O bonds lengths, as well as shortened C-N bonds. An intramolecular N-H...O hydrogen bond stabilizes the molecular conformation. In the crystal, molecules are connected by N-H...O and N-H...S hydrogen bonds, forming chains running along the alpha axis. Key indicators: single-crystal X-ray study; T = 173 K; mean σ (C–C) = 0.002 Å; disorder in main residue; R factor = 0.035; wR factor = 0.087; data-to-parameter ratio = 18.9

1-(3-Chloro­phen­yl)-3-(2,6-dichloro­benzo­yl)thio­urea

The structure of the title compound, C14H9Cl3N2OS, is composed of discrete mol­ecules with bond lengths and angles quite typical for thio­urea compounds of this class. The plane containing the thio­carbonyl and carbonyl groups subtends dihedral angles of 48.19 (3) and 87.51 (3)° with the planes formed by the 3-chloro and 2,6-dichloro­phenyl rings, respectively; the dihedral angle between the two benzene ring planes is 45.32 (3)°. An intra­molecular N—H⋯O hydrogen bond stabilizes the mol­ecular conformation and the mol­ecules form inter­molecular N—H⋯S and N—H⋯O hydrogen bonds, generating a sheet along the a axis

1-(2,6-Dichloro­benzo­yl)-3-(2,3,5,6-tetra­chloro­phen­yl)thio­urea trichloro­methane hemisolvate

The title compound, C14H6Cl6N2OS·0.5CHCl3, crystallizes with four 1-(2,6-dichloro­benzo­yl)-3-(2,3,5,6-tetra­chloro­phen­yl)thio­urea mol­ecules and two trichloro­methane mol­ecules in the asymmetric unit. The thiourea molecules exist in the solid state in their thione forms with typical thio­urea C—S and C—O bonds lengths, as well as shortened C—N bonds. The —NH—C(=S)—NH—C(=O)— plane is almost perpen­dicular to the benzene ring in each thiourea molecule. Intra­molecular N—H⋯O hydrogen bonds stabilize the mol­ecular conformation and inter­molecular N—H⋯S hydrogen bonds stabilize the packing arrangement

1-(4-Chloro­phen­yl)-3-(2,4-dichloro­benzo­yl)thio­urea

The title compound, C14H9Cl3N2OS, has bond lengths and angles which are quite typical for thio­urea compounds of this class. The mol­ecule exists in the solid state in its thione form with typical thio­urea C=S and C=O bond lengths, as well as shortened C—N bonds. An intra­molecular N—H⋯O hydrogen bond stabilizes the mol­ecular conformation. Inter­molecular N—H⋯S hydrogen bonds link the mol­ecules to form centrosymmetric dimers

1-(2,6-Dichloro­benzo­yl)-3-(3,5-dichloro­phen­yl)thio­urea

The crystal structure of the title compound, C14H8Cl4N2OS, is composed of discrete mol­ecules with bond lengths and angles quite typical for thio­urea compounds of this class. The plane containing the central SONNCC atom set subtends a dihedral angle of 31.47 (3)° with the benzene ring. An intra­molecular N—H⋯O hydrogen bond stabilizes the mol­ecular conformation and the mol­ecules form centrosymmetric dimers via inter­molecular N—H⋯S hydrogen bonds

Immune checkpoints in circulating and tumor-Infiltrating CD4 + T Cell Subsets in Colorectal cancer patients

Blockade of inhibitory immune checkpoints (ICs) is a promising therapeutic approach; however, it has shown limited success in some cancers including colorectal cancer (CRC). The tumor microenvironment (TME) is largely responsible for response to therapy, and its constituents may provide robust biomarkers for successful immunotherapeutic approaches. In this study, we performed phenotypical characterization and critical analyses of key inhibitory ICs and T regulatory cell (Treg)-related markers on CD4+ T cell subsets in CRC patients, and compared with normal colon tissues and peripheral blood from the same patients. We also investigated correlations between the levels of different CD4+ T cell subsets and the clinicopathologic features including disease stage and tumor budding. We found a significant increase in the levels of CD4+FoxP3+Helios+ T cells, which represent potentially highly immunosuppressive Tregs, in the CRC TME. Additionally, tumor-infiltrating CD4+ T cells upregulated programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), T cell immunoglobulin and mucin domain-3 (TIM-3) and lymphocyte-activation gene 3 (LAG-3). We also characterized the expression of PD-1, CTLA-4, TIM-3, and LAG-3 on different CD4+FoxP3−/+Helios−/+ T cell subsets. Interestingly, we found that CTLA-4, TIM-3, and LAG-3 were mainly co-expressed on FoxP3+Helios+ Tregs in the TME. Additionally, FoxP3high Tregs expressed higher levels of Helios, CTLA-4 and TIM-3 than FoxP3low T cells. These results highlight the significance of Tregs in the CRC TME and suggest that Tregs may hamper response to IC blockade in CRC patients, but effects of different IC inhibition regimes on Treg levels or activity warrants further investigations. We also found that CD4+CTLA-4+ T cells in circulation are increased in patients with advanced disease stage. This study simultaneously provides important insights into the differential levels of CD4+ T cell subpopulations and IC expression in CRC TME, compared to periphery and associations with clinicopathologic features, which could be used as potential biomarkers for CRC progression and response to therapy

Expert review on coronary calcium

While there is no doubt that high risk patients (those with >20% ten year risk of future cardiovascular event) need more aggressive preventive therapy, a majority of cardiovascular events occur in individuals at intermediate risk (10%–20% ten year risk). Accurate risk assessment may be helpful in decreasing cardiovascular events through more appropriate targeting of preventive measures. It has been suggested that traditional risk assessment may be refined with the selective use of coronary artery calcium (CAC) or other methods of subclinical atherosclerosis measurement. Coronary calcification is a marker of atherosclerosis that can be quantified with the use of cardiac CT and it is proportional to the extent and severity of atherosclerotic disease. The published studies demonstrate a high sensitivity of CAC for the presence of coronary artery disease but a lower specificity for obstructive CAD depending on the magnitude of the CAC. Several large clinical trials found clear, incremental predictive value of CAC over the Framingham risk score when used in asymptomatic patients. Based on multiple observational studies, patients with increased plaque burdens (increased CAC) are approximately ten times more likely to suffer a cardiac event over the next 3–5 years. Coronary calcium scores have outperformed conventional risk factors, highly sensitive C-reactive protein (CRP) and carotid intima media thickness (IMT) as a predictor of cardiovascular events. The relevant prognostic information obtained may be useful to initiate or intensify appropriate treatment strategies to slow the progression of atherosclerotic vascular disease. Current data suggests intermediate risk patients may benefit most from further risk stratification with cardiac CT, as CAC testing is effective at identifying increased risk and in motivating effective behavioral changes. This article reviews information pertaining to the clinical use of CAC for assessing coronary atherosclerosis as a useful predictor of coronary artery disease (CAD) in certain population of patients