Tim-3 mediates T cell trogocytosis to limit antitumor immunity

T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) negatively regulates innate and adaptive immunity in cancer. To identify the mechanisms of Tim-3 in cancer immunity, we evaluated the effects of Tim-3 blockade in human and mouse melanoma. Here, we show that human programmed cell death 1–positive (PD-1⁺) Tim-3⁺CD8⁺ tumor-infiltrating lymphocytes (TILs) upregulate phosphatidylserine (PS), a receptor for Tim-3, and acquire cell surface myeloid markers from antigen-presenting cells (APCs) through transfer of membrane fragments called trogocytosis. Tim-3 blockade acted on Tim-3⁺ APCs in a PS-dependent fashion to disrupt the trogocytosis of activated tumor antigen–specific CD8⁺ T cells and PD-1⁺Tim-3⁺ CD8⁺ TILs isolated from patients with melanoma. Tim-3 and PD-1 blockades cooperated to disrupt trogocytosis of CD8⁺ TILs in 2 melanoma mouse models, decreasing tumor burden and prolonging survival. Deleting Tim-3 in dendritic cells but not in CD8⁺ T cells impeded the trogocytosis of CD8⁺ TILs in vivo. Trogocytosed CD8⁺ T cells presented tumor peptide–major histocompatibility complexes and became the target of fratricide T cell killing, which was reversed by Tim-3 blockade. Our findings have uncovered a mechanism Tim-3 uses to limit antitumor immunity.     

Prognostic value of negative dobutamine stress echo in women with intermediate probability of coronary artery disease

Women with an intermediate pretest probability of coronary artery disease represent a significant proportion of patients referred for the investigation of chest pain. Dobutamine stress echocardiography can be used to restratify these patients into a low-risk group without resorting to cardiac catheterization.     

Antidepressant drug treatment for poststroke depression: retrospective study

The records of 60 patients evaluated psychiatrically for major depression after stroke were reviewed retrospectively. Forty-two patients were treated with one of several "cyclic" antidepressant drugs, and 18 received no drug treatment. Objective ratings, based on current standard criteria for "major depression" (DSM-III), were used to establish degree of depression at initial evaluation and within six weeks after the start of treatment. Overall, improvement in depression was no greater in treated than in untreated patients. However, a subgroup (40%) of drug-treated patients was identified with a substantial (greater than or equal to 40%) improvement in depression ratings. Only three (17%) untreated patients showed a comparable improvement within a similar time period. Eighteen (43%) of the drug-treated patients experienced minor side effects (especially mild sedation), but only three (7%) experienced major side effects that required cessation of treatment. The degree of initial depression was not correlated with the degree of motor or functional disability among patients. These results suggest that antidepressants may constitute safe and effective treatment for some patients with poststroke depression, and further studies of the pathophysiology and treatment of this disorder are indicated.     

Computational Fluid Dynamics Study of the Effects of Surface Roughness on Permeability and Fluid Flow-Induced Wall Shear Stress in Scaffolds

In this work, we investigated surface roughness effects on bone scaffold permeability and fluid flow-induced wall shear stress (WSS) using computational fluid dynamics (CFD) analysis. Scaffolds are made of interconnected microchannels, whose fluid flow can be examined from the perspective of fluid flow dynamics. Given that the roughness of microchannel surfaces serves a non-negligible function in the fluid dynamics within the channels, it is believed that the wall roughness of scaffolds can play an important role in their permeability and WSS. Given the criticality of permeability and WSS in the effective biological functioning of scaffolds, we investigated manufacturing-induced surface roughness effects on the two aforementioned biocompatibility characteristics. To this end, three scaffolds with square pores of different sizes (300, 600, and 900 µm) and identical porosity (63%) were designed. Six roughness levels (0, 4, 8, 12, 16, and 20 µm) were established for the scaffold walls, thus enabling us to develop 18 scaffold models. The pressure drop and WSS in the scaffolds were then measured by CFD. Scaffold permeability was calculated using Darcy’s law, with reference to geometrical parameters and the pressure drop derived from the CFD analysis. In all the scaffolds, high roughness decreased permeability and WSS. A significant difference in WSS reduction was found between the models with smooth scaffolds and the models with scaffolds that had a roughness of 20 µm. Except for the scaffold with a pore size of 300 µm, all the others showed no considerable change in permeability at different roughness levels.     

A DFT study on nanocones,nanotubes (4,0), nanosheets and fullerene C60 as anodes in Mg-ion batteries

In this article, we studied the interactions between Mg atom and Mg²⁺ ion and four nanostructures, including a nanocone, nanotube (4,0), nanosheet, and C₆₀ nanocage, to obtain the cell voltages (V) for Mg-ion batteries (MIBs). Total energy, geometry optimization, frontier molecular orbital (FMO) and density of states (DOS) analyses have been performed using the ωB97XD level of theory and the 6-31G(d) basis set. The DFT calculations clarified that the changes in energy adsorption between Mg²⁺ ion and the nanostructures, E_ad, are in the order tube > cone > sheet > cage. However, V_cell for the nanocone is the highest. The changes in V_cell of the MIBs are in the order cone > tube > sheet > cage. This study theoretically considers the possibilities of Mg as an anode in batteries due to its high V_cell values.

In this article, we studied the interactions between Mg atom and Mg²⁺ ion and four nanostructures, including a nanocone, nanotube (4,0), nanosheet, and C₆₀ nanocage, to obtain the cell voltages (V) for Mg-ion batteries (MIBs).     

Behavioral evidence of thermal hyperalgesia in non-obese diabetic mice with and without insulin-dependent diabetes

The non-obese diabetic (NOD) mouse, a model of Type 1 diabetes in humans, has proven useful for the study of genetic, immunologic and epidemiologic aspects of inherited diabetes. Behavioral evidence of hyperalgesia may also be present in the NOD mouse but has not been described. This study examined NOD mice with (NOD+) and without (NOD−) insulin-dependent diabetes, and control strain (ILI) mice for evidence of hyperalgesia to a noxious thermal stimulus. Interestingly, both NOD+ and NOD− mice showed reduced mean hindpaw withdrawal latencies when compared with non-diabetic ILI mice. NOD+ and NOD− mice were also abnormal in their general appearance, activity level, posture, gait and muscle bulk when compared with ILI mice. These findings raise the possibility that hyperalgesia in insulin-dependent NOD mice, or insulin-dependent humans with Type 1 diabetes, may be independent of diabetes and due to a primary disturbance within sensory pathways.