Bezafibrate Rescues Mitochondrial Encephalopathy in Mice via Induction of Daily Torpor and Hypometabolic State.

Leigh syndrome (LS) is one of the most common mitochondrial encephalopathy diseases in infants. To date, there is still an absence of effective therapy. Bezafibrate (BEZ), a pan-peroxisome proliferator-activated receptor (PPAR) agonist, ameliorates the phenotype of the mouse model of mitochondrial disease via an unclear mechanism. Here, we applied it to Ndufs4 knockout (KO) mice, a widely used LS animal model, to observe the therapeutic effects and metabolic changes associated with BEZ treatment to explore the therapeutic strategies for mitochondrial diseases. Administration of BEZ significantly enhances survival and attenuates disease progression in Ndufs4 KO mice. Decreased oxidative stress and stunted growth were also observed. As a PPAR agonist, we did not find mitochondrial biogenesis or enhanced metabolism upon BEZ treatment. On the contrary, mice with dietary BEZ showed daily torpor bouts and lower metabolic rates. We speculate that activating energy-saving metabolism in mice may be associated with the therapeutic effects of BEZ, but the exact mechanism of action requires further study.

Highly Efficient Capture and Quantification of the Airborne Fungal Pathogen Sclerotinia sclerotiorum Employing a Nanoelectrode-Activated Microwell Array.

In this study, we present a microdevice for the capture and quantification of Sclerotinia sclerotiorum spores, pathogenic agents of one of the most harmful infectious diseases of crops, Sclerotinia stem rot. The early prognosis of an outbreak is critical to avoid severe economic losses and can be achieved by the detection of a small number of airborne spores. However, the current lack of simple and effective methods to quantify fungal airborne pathogens has hindered the development of an accurate early warning system. We developed a device that remedies these limitations based on a microfluidic design that contains a nanothick aluminum electrode structure integrated with a picoliter well array for dielectrophoresis-driven capture of spores and on-chip quantitative detection employing impedimetric sensing. Based on experimental results, we demonstrated a highly efficient spore trapping rate of more than 90% with an effective impedimetric sensing method that allowed the spore quantification of each column in the array and achieved a sensitivity of 2%/spore at 5 kHz and 1.6%/spore at 20 kHz, enabling single spore detection. We envision that our device will contribute to the development of a low-cost microfluidic platform that could be integrated into an infectious plant disease forecasting tool for crop protection.

Activated mTOR signaling pathway in myofibers with inherited metabolic defect might be an evidence for mTOR inhibition therapies.

BACKGROUND: Abnormally activated mechanistic target of rapamycin (mTOR) pathway has been reported in several model animals with inherited metabolic myopathies (IMMs). However, the profiles of mTOR pathway in skeletal muscles from patients are still unknown. This study aimed to analyze the activity of mTOR pathway in IMMs muscles. METHODS: We collected muscle samples from 25 patients with mitochondrial myopathy (MM), lipid storage disease (LSD) or Pompe disease (PD). To evaluate the activity of mTOR pathway in muscle specimens, phosphorylation of S6 ribosomal protein (p-S6) and p70S6 kinase (p-p70S6K) were analyzed by Western blotting and immunohistochemistry. RESULTS: Western blotting results showed that p-p70S6K/p70S6K in muscles from LSD and MM was up-regulated when compared with normal controls (NC) (NC vs. LSD, U = 2.000, P = 0.024; NC vs. MM: U = 6.000, P = 0.043). Likewise, p-S6/S6 was also up-regulated in muscles from all three subgroups of IMMs (NC vs. LSD, U = 0.000, P = 0.006; NC vs. PD, U = 0.000, P = 0.006; NC vs. MM, U = 1.000, P = 0.007). Immunohistochemical study revealed that p-S6 was mainly expressed in fibers with metabolic defect. In MM muscles, most p-S6 positive fibers showed cytochrome C oxidase (COX) deficiency (U = 5.000, P = 0.001). In LSD and PD muscles, p-S6 was mainly overexpressed in fibers with intramuscular vacuoles containing lipid droplets (U = 0.000, P = 0.002) or basophilic materials (U = 0.000, P = 0.002). CONCLUSION: The mTOR pathway might be activated in myofibers with various metabolic defects, which might provide evidence for mTOR inhibition therapy in human IMMs.