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Kathajodi, the principal southern distributary of the Mahanadi River, is the vital source of irrigation and domestic water use for densely populated Cuttack city which receives anthropogenic wastes abundantly. This study assesses the contamination level and primary health status of urban wastewater, and its receiving river Kathajodi based on the physicochemical quality indices employing inductively coupled plasma mass spectroscopy and aligning with guidelines from the United States Environmental Protection Agency (USEPA) and WHO. The high WQI, HPI, and HEI in the catchment area (KJ2, KJ3, and KJ4) indicate poor water quality due to the influx of domestic waste through the primary drainage system and effluents of healthcare units. A high BOD (4.33-19.66 mg L -1 ) in the catchment indicates high organic matter, animal waste, bacteriological contamination, and low DO, resulting in deterioration of water quality. CR values beyond limits (1.00E - 06 to 1.00E - 04) in three locations of catchment due to higher Cd, Pb, and As indicate significant carcinogenic risk, while high Mn, Cu, and Al content is responsible for several non-carcinogenic ailments and arsenic-induced physiological disorders. The elevated heavy metals Cd, Cu, Fe, Mn, Ni, and Zn, in Kathajodi, could be due to heavy coal combustion, vehicle exhaust, and industrial waste. On the other hand, Cu, Fe, K, and Al could be from agricultural practices, weathered rocks, and crustal materials. Positive significant (p ≤ 0.05) Pearson correlations between physicochemical parameters indicate their common anthropogenic origin and similar chemical characteristics. A strong correlation of PCA between elements and physiological parameters indicates their role in water quality deterioration. Assessing the surface water quality and heavy metal contents from this study will offer critical data to policymakers for monitoring and managing public health concerns., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Mitochondrial fitness is governed by mitochondrial quality control pathways comprising mitochondrial dynamics and mitochondrial-selective autophagy (mitophagy). Disruption of these processes has been implicated in many human diseases, including viral infections. Here, we report a comprehensive analysis of the effect of dengue infection on host mitochondrial homeostasis and its significance in dengue disease pathogenesis. Despite severe mitochondrial stress and injury, we observed that the pathways of mitochondrial quality control and mitochondrial biogenesis are paradoxically downregulated in dengue-infected human liver cells. This leads to the disruption of mitochondrial homeostasis and the onset of cellular injury and necrotic death in the infected cells. Interestingly, dengue promotes global autophagy but selectively disrupts mitochondrial-selective autophagy (mitophagy). Dengue downregulates the expression of PINK1 and Parkin, the two major proteins involved in tagging the damaged mitochondria for elimination through mitophagy. Mitophagy flux assays also suggest that Parkin-independent pathways of mitophagy are also inactive during dengue infection. Dengue infection also disrupts mitochondrial biogenesis by downregulating the master regulators PPARγ and PGC1α. Dengue-infected cells release mitochondrial damage-associated molecular patterns (mtDAMPs) such as mitochondrial DNA into the cytosol and extracellular milieu. Furthermore, the challenge of naive immune cells with culture supernatants from dengue-infected liver cells was sufficient to trigger proinflammatory signaling. In correlation with our in vitro observations, dengue patients have high levels of cell-free mitochondrial DNA in their blood in proportion to the degree of thrombocytopenia. Overall, our study shows how defective mitochondrial homeostasis in dengue-infected liver cells can drive dengue disease pathogenesis. IMPORTANCE Many viruses target host cell mitochondria to create a microenvironment conducive to viral dissemination. Dengue virus also exploits host cell mitochondria to facilitate its viral life cycle. Dengue infection of liver cells leads to severe mitochondrial injury and inhibition of proteins that regulate mitochondrial quality control and biogenesis, thereby disrupting mitochondrial homeostasis. A defect in mitochondrial quality control leads to the accumulation of damaged mitochondria and promotes cellular injury. This leads to the release of mitochondrial damage-associated molecular patterns (mt-DAMPs) into the cell cytoplasm and extracellular milieu. These mt-DAMPs activate the naive immune cells and trigger proinflammatory signaling, leading to the release of cytokines and chemokines, which may trigger systemic inflammation and contribute to dengue disease pathogenesis. In correlation with this, we observed high levels of cell-free mitochondrial DNA in dengue patient blood. This study provides insight into how the disruption of mitochondrial quality control in dengue-infected cells can trigger inflammation and drive dengue disease pathogenesis.