Small molecule agonist of mitochondrial fusion repairs mitochondrial dysfunction.

Membrane dynamics are important to the integrity and function of mitochondria. Defective mitochondrial fusion underlies the pathogenesis of multiple diseases. The ability to target fusion highlights the potential to fight life-threatening conditions. Here we report a small molecule agonist, S89, that specifically promotes mitochondrial fusion by targeting endogenous MFN1. S89 interacts directly with a loop region in the helix bundle 2 domain of MFN1 to stimulate GTP hydrolysis and vesicle fusion. GTP loading or competition by S89 dislodges the loop from the GTPase domain and unlocks the molecule. S89 restores mitochondrial and cellular defects caused by mitochondrial DNA mutations, oxidative stress inducer paraquat, ferroptosis inducer RSL3 or CMT2A-causing mutations by boosting endogenous MFN1. Strikingly, S89 effectively eliminates ischemia/reperfusion (I/R)-induced mitochondrial damage and protects mouse heart from I/R injury. These results reveal the priming mechanism for MFNs and provide a therapeutic strategy for mitochondrial diseases when additional mitochondrial fusion is beneficial.

Research on an anti-motion interference algorithm of blood oxygen saturation based on AC and DC analysis.

BACKGROUND: There is an urgent need for blood oxygen saturation (SpO2) tests when participants are ambulatory, as in daily activity monitoring, sleep monitoring, or even athletes' cardiovascular function tests. In such situations, measuring equipment needs to be wearable. This restricts the processor volume, and the corresponding algorithm should be microprocessor compatible. OBJECTIVE: This article proposes an anti-motion interference blood oxygen saturation algorithm for the microcontroller based on AC and DC analysis, named de-trended FFT. METHODS: An experiment was conducted to compare the de-trended FFT algorithm with two other algorithms commonly used in the time and frequency domains. In the experiment, participants' oxygen saturation levels were calculated from Photoplethysmography (PPG) signals that were recorded continuously. Meantime, five types of hand motions were conducted, including hand trembling movements, horizontal hand movements, vertical hand movements, finger tapping, and finger bending, with each state lasting 2 minutes. RESULTS: Results show significant performance of de-trended FFT in SpO2 calculation (P < 0.05), in both accuracy and stability. CONCLUSION: De-trended FFT stands out in both mean deviation and variance by eliminating trending influence when compared with the other two algorithms. The motion interference's influence on SpO2 calculation mainly comes from the AC component, not the DC.

[CALM-AF10 fusion transcripts in primary leukemia with t(10;11) and in vitro chemotherapy sensitivity of leukemic cells with t(10;11)].

In order to determine the involvement of CALM-AF10 fusion transcripted in primary leukaemias with t(10;11) and its chemotherapy sensitivity in vitro, the AF10-CALM fusion transcripts were detected by reverse transcription-polymerase chain reaction (RT-PCR), and the chemotherapy sensitivity testing in vitro was undergone by MTT assay in five t(10;11) leukemia samples from patients with ALL, AML and lymphoblastic lymphoma. The results showed that five different-sized AF10-CALM product and four different-sized CALM-AF10 products were detected. The chemotherapy sensitivity of leukemic cells with t(10;11) in vitro to drugs is lower than that of leukemic cells without t(10;11). 3 out of 5 cases of t(10;11) leukemia were sensitive to chemotherapeutic drugs, while 31 out of 36 cases of leukemia without t(10;11) were sensitive at same condition. There were significant differences (P < 0.01), consistent with clinical features of patients. Apoptosis rate of leukemic cells with t(10;11) induced by chemotherapeutic drugs was lower than that of leukemic cells without t(10;11), (16.37 +/- 2.56)%, and (33.75 +/- 5.59)%, respectively (P < 0.01). It is concluded that the CALM-AF10 fusion transcripts are a common features and are involved in the pathogenesis of haematological malignancies with t(10;11), and are associated with a poor prognosis.