Intracellular chloride channels regulate endothelial metabolic reprogramming in pulmonary arterial hypertension

Mitochondrial fission and a metabolic switch from oxidative phosphorylation to glycolysis are key features of vascular pathology in pulmonary arterial hypertension (PAH) and are associated with exuberant endothelial proliferation and apoptosis. The underlying mechanisms are poorly understood. We describe the contribution of two intracellular chloride channel proteins CLIC1 and CLIC4, both highly expressed in PAH and cancer, to mitochondrial dysfunction and energy metabolism in PAH endothelium. Pathological overexpression of CLIC proteins induces mitochondrial fragmentation, inhibits mitochondrial cristae formation and induces metabolic shift towards glycolysis in human pulmonary artery endothelial cells, consistent with changes observed in patient-derived cells. Interactions of CLIC proteins with structural components of the inner mitochondrial membrane offer mechanistic insights. Endothelial CLIC4 excision and mitofusin 2 supplementation have protective effects in human PAH cells and pre-clinical PAH. This study is first to demonstrate the key role of endothelial intracellular chloride channels in the regulation of mitochondrial structure, biogenesis, and metabolic reprogramming in expression of the PAH phenotype

Non-Invasive Brain Sensing Technologies for Modulation of Neurological Disorders

The non-invasive brain sensing modulation technology field is experiencing rapid development, with new techniques constantly emerging. This study delves into the field of non-invasive brain neuromodulation, a safer and potentially effective approach for treating a spectrum of neurological and psychiatric disorders. Unlike traditional deep brain stimulation (DBS) surgery, non-invasive techniques employ ultrasound, electrical currents, and electromagnetic field stimulation to stimulate the brain from outside the skull, thereby eliminating surgery risks and enhancing patient comfort. This study explores the mechanisms of various modalities, including transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), highlighting their potential to address chronic pain, anxiety, Parkinson’s disease, and depression. We also probe into the concept of closed-loop neuromodulation, which personalizes stimulation based on real-time brain activity. While we acknowledge the limitations of current technologies, our study concludes by proposing future research avenues to advance this rapidly evolving field with its immense potential to revolutionize neurological and psychiatric care and lay the foundation for the continuing advancement of innovative non-invasive brain sensing technologies

Hospitality and tourism management: adopting Lean Six Sigma, achieving service excellence

The hospitality and tourism industry is very much people-driven, despite the incipient advances and adoption of technology. Given the increased integration of the latter into the service sector, there must be ways to measure or calibrate the quality of service in the industry. Because tourism is a business like any other and compounded by mobility, a business management system approach to performance analysis and process adjustment can be adopted. One such management system is the Lean Six Sigma, which is a process method to improve the efficiency of business operations, in order to achieve high customer satisfaction (Farrington et al. 2018). This method allows experts in the tourism and hospitality business to identify product and operations deficiencies, and thereby enhance service quality and standards, thus leading to service excellence in the industry. Much research has been conducted on the application of Lean Six Sigma in industries such as logistics and sales (Gutierrez- Gutierrez et al. 2016; Zhang et al. 2016), financial, healthcare, and retail. The goal of this paper is to shed light on the possibility of the tourism and hospitality sector adopting a management system such as Lean Six Sigma as a continuous improvement method to achieve service excellence (Ivasciuc and Epuran 2015; Basu 2011; Farrington et al. 2018). The basic rationale of Lean Management is to reduce non-value-adding components of processes, and maintain only processes which add direct value to the company’s customers (Kaufmann 2012)