Alterations in sorting and secretion of hepatic apoA5 induce hypertriglyceridemia due to short-term use of olanzapine.

Long-term use of olanzapine, an antipsychotic drug, induces hypertriglyceridemia, resulting in a higher risk of cardiovascular disease. However, the effects and underlying mechanisms of short-term use of olanzapine on circulating triglyceride levels remain poorly understood. Here, the role of apolipoprotein A5 (apoA5), a regulator of triglyceride metabolism, was investigated in olanzapine-induced hypertriglyceridemia. Our multi-center clinical study recruited 36 schizophrenia patients who received short-term (8 weeks) of olanzapine. Besides, female C57BL/6J mice were treated with olanzapine (3 mg/kg/day versus 6 mg/kg/day) for 6 weeks. We demonstrated that short-term use of olanzapine increased plasma triglyceride and decreased plasma apoA5 levels in the patients and mice, with a negative correlation between the two factors. However, no obesity was observed in the patients and mice. Interestingly, olanzapine increased hepatic apoA5 protein in the mice, without significant changes in hepatic Apoa5 mRNA. Consistently, in vitro studies indicated that olanzapine increased medium triglyceride levels and decreased medium apoA5 levels in a dose-dependent manner in human HepG2 cells and primary mouse hepatocytes. Whereas the olanzapine treatment increased hepatic apoA5 protein in vitro, without effects on hepatic APOA5 mRNA. Of note, olanzapine increased the co-localization between apoA5 protein and accumulated lipid droplets in hepatocytes, as opposed to at the hepatocellular plasma membrane, in mouse liver as demonstrated by fluorescence staining. Therefore, our study indicated that short-term use of olanzapine induced hypertriglyceridemia due to defects of sorting and secretion of hepatic apoA5.

A Rare Case of Isolated Right Ventricular Non-compaction With the Novel TTN Mutation.

Isolated right ventricular non-compaction (RVNC) is rare yet life-threatening if left untreated, especially when accompanied by ventricular tachycardia. We describe a rare case of isolated RVNC, presenting as a prominent and excessive trabeculation of the right ventricle (RV), with an abnormal electrocardiogram. The transthoracic echocardiography, computed tomography, and ventricular angiography results clearly demonstrated an isolated spongy RV, both anatomically and functionally. Genetic testing identified a missense mutation of TTN. Combined, the diagnosis of RVNC was established. The subsequent combination of heart failure therapy, antiarrhythmic, and anticoagulation therapy were effective with a favorable outcome. This case report describes the possible etiology, manifestation, characteristic images, and problematic diagnostic criteria of the isolated RVNC. This case also emphasizes the necessity for comprehensive cardiac screening in familial cardiomyopathy.

Fano effect in a one-dimensional photonic lattice with side-coupled P T-symmetric non-Hermitian defects.

We theoretically study the transport properties in a one-dimensional photonic lattice influenced by the presence of side-coupled P T-symmetric non-Hermitian defects. The P T symmetry is manifested as the complex potentials on the defects and the complex defect-lattice couplings, respectively. These two mechanisms are found to induce the Fano effect in the transport processes, with the different characteristics of it. Next, if the complex potentials and defect-lattice couplings co-exist, the Fano effect will be achieved more efficiently. However, further enhancing either of them can weaken the Fano interference seriously. Our findings reveal the physical essence of the Fano effect on the P T-symmetric non-Hermitian defects, and the results can provide insights into the engineering and dynamical control of Fano resonances in non-Hermitian photonic structures.