Endogenous complement 1q binding protein (C1qbp) regulates mitochondrial permeability transition and post-myocardial infarction remodeling and dysfunction.

The mitochondrial permeability transition (MPT) pore regulates necrotic cell death following diverse cardiac insults. While the componentry of the pore itself remains controversial, Cyclophilin D (CypD) has been well-established as a positive regulator of pore opening. We have previously identified Complement 1q-binding protein (C1qbp) as a novel CypD-interacting molecule and a negative regulator of MPT-dependent cell death in vitro. However, its effects on the MPT pore and sensitivity to cell death in the heart remain untested. We therefore hypothesized that C1qbp would inhibit MPT in cardiac mitochondria and protect cardiac myocytes against cell death in vivo. To investigate the effects of C1qbp in the myocardium we generated gain- and loss-of-function mice. Transgenic C1qbp overexpression resulted in decreased complex protein expression and reduced mitochondrial respiration and ATP production but MPT was unaffected. In contrast, while C1qbp+/- mice did not exhibit any changes in mitochondrial protein expression, respiration, or ATP, the MPT pore was markedly sensitized to Ca2+ in these animals. Neither overexpression nor depletion of C1qbp significantly affected baseline heart morphology or function at 3 months of age. When subjected to myocardial infarction, C1qbp transgenic mice exhibited similar infarct sizes and cardiac remodeling to non-transgenic mice, consistent with the lack of an effect on MPT. In contrast, cardiac scar formation and dysfunction were significantly increased in the C1qbp+/- mice compared to C1qbp+/+ controls. Our results suggest that C1qbp is required for normal regulation of the MPT pore and mitochondrial function, and influences cardiac remodeling following MI, the latter more likely being independent of C1qbp effects on the MPT pore.

What Influences the Patients with Left Atrial Myxoma: From Embolism to Postoperative Atrial Fibrillation.

BACKGROUND: Preoperative embolism and postoperative atrial fibrillation (POAF) are two important factors associated with impaired health conditions and increased economic burden in patients with left atrial (LA) myxoma. The aim of this study was to analyze embolic events, identify predictors of POAF, and evaluate the risk of late-term survival in patients with LA myxoma. METHODS: From December 2009 to December 2019, 177 consecutive patients with LA myxoma who met the selection criteria were included in the retrospective analysis. Multivariate logistic regression analysis was performed to identify predictors of POAF. Propensity score matching was used for confounder control, and Cox proportional hazards models were used to evaluate the risk of late-term mortality. RESULTS: The study population comprised of 125 patients in non-POAF group and 52 patients in POAF group. Preoperative embolism was present in 27.1% of the all cases. By multivariate analysis, age, NYHA functional class III, LA diameter, and cross-clamp time were identified as independent predictors of in-hospital POAF. The overall survival at 1, 5, and 10 years for the 177 patients was 98.9%, 93.7%, and 84.4%, respectively. There was no statistical difference in late-term survival between the two groups in the Cox proportion-adjusted survival curve. After propensity score 1:1 matching, patients with POAF had a longer postoperative hospital stay and Kaplan-Meier survival curve also showed no statistical difference between the two groups. CONCLUSIONS: Patients with LA myxoma after surgical treatment had a favorable prognosis. In-hospital POAF was not independently associated with late-term mortality in patients with LA myxoma.

The novel cyclophilin-D-interacting protein FASTKD1 protects cells against oxidative stress-induced cell death.

Opening of the mitochondrial permeability transition (MPT) pore leads to necrotic cell death. Excluding cyclophilin D (CypD), the makeup of the MPT pore remains conjecture. The purpose of these experiments was to identify novel MPT modulators by analyzing proteins that associate with CypD. We identified Fas-activated serine/threonine phosphoprotein kinase domain-containing protein 1 (FASTKD1) as a novel CypD interactor. Overexpression of FASTKD1 protected mouse embryonic fibroblasts (MEFs) against oxidative stress-induced reactive oxygen species (ROS) production and cell death, whereas depletion of FASTKD1 sensitized them. However, manipulation of FASTKD1 levels had no effect on MPT responsiveness, Ca2+-induced cell death, or antioxidant capacity. Moreover, elevated FASTKD1 levels still protected against oxidative stress in CypD-deficient MEFs. FASTKD1 overexpression decreased Complex-I-dependent respiration and ΔΨm in MEFs, effects that were abrogated in CypD-null cells. Additionally, overexpression of FASTKD1 in MEFs induced mitochondrial fragmentation independent of CypD, activation of Drp1, and inhibition of autophagy/mitophagy, whereas knockdown of FASTKD1 had the opposite effect. Manipulation of FASTKD1 expression also modified oxidative stress-induced caspase-3 cleavage yet did not alter apoptotic death. Finally, the effects of FASTKD1 overexpression on oxidative stress-induced cell death and mitochondrial morphology were recapitulated in cultured cardiac myocytes. Together, these data indicate that FASTKD1 supports mitochondrial homeostasis and plays a critical protective role against oxidant-induced death.

Separating Leaf and Wood Points in Terrestrial Laser Scanning Data Using Multiple Optimal Scales.

The separation of leaf and wood points is an essential preprocessing step for extracting many of the parameters of a tree from terrestrial laser scanning data. The multi-scale method and the optimal scale method are two of the most widely used separation methods. In this study, we extend the optimal scale method to the multi-optimal-scale method, adaptively selecting multiple optimal scales for each point in the tree point cloud to increase the distinctiveness of extracted geometric features. Compared with the optimal scale method, our method achieves higher separation accuracy. Compared with the multi-scale method, our method achieves more stable separation accuracy with a limited number of optimal scales. The running time of our method is greatly reduced when the optimization strategy is applied.

Cardiac Myocyte-Specific Overexpression of FASTKD1 Prevents Ventricular Rupture After Myocardial Infarction.

Background The mitochondrial mRNA-binding protein FASTKD1 (Fas-activated serine/threonine [FAST] kinase domain-containing protein 1) protects myocytes from oxidative stress in vitro. However, the role of FASTKD1 in the myocardium in vivo is unknown. Therefore, we developed cardiac-specific FASTKD1 transgenic mice to test the effects of this protein on experimental myocardial infarction (MI). Methods and Results Transgenic mouse lines with cardiac myocyte-specific overexpression of FASTKD1 to varying degrees were generated. These mice displayed normal cardiac morphological features and function at the gross and microscopic levels. Isolated cardiac mitochondria from all transgenic mouse lines showed normal mitochondrial function, ATP levels, and permeability transition pore activity. Male nontransgenic and transgenic mice from the highest-expressing line were subjected to 8 weeks of permanent coronary ligation. Of nontransgenic mice, 40% underwent left ventricular free wall rupture within 7 days of MI compared with 0% of FASTKD1-overexpressing mice. At 3 days after MI, FASTKD1 overexpression did not alter infarct size. However, increased FASTKD1 resulted in decreased neutrophil and increased macrophage infiltration, elevated levels of the extracellular matrix component periostin, and enhanced antioxidant capacity compared with control mice. In contrast, markers of mitochondrial fusion/fission and apoptosis remained unaltered. Instead, transcriptomic analyses indicated activation of the integrated stress response in the FASTKD1 transgenic hearts. Conclusions Cardiac-specific overexpression of FASTKD1 results in viable mice displaying normal cardiac morphological features and function. However, these mice are resistant to MI-induced cardiac rupture and display altered inflammatory, extracellular matrix, and antioxidant responses following MI. Moreover, these protective effects were associated with enhanced activation of the integrated stress response.

Graphene-based strain sensor with sandwich structure and its application in bowel sounds monitoring.

Surgery is one of the primary treatment modalities for gastrointestinal tumors but can lead to postoperative ileus (POI), which can aggravate pain and increase costs. The incidence of POI can be effectively reduced by monitoring bowel sounds to assist doctors in deciding the timing of transoral feeding. In this study, we prepared a flexible strain sensor based on a graphene composite material and tested the feasibility of sensor monitoring of bowel sounds using simultaneous stethoscope and sensor monitoring. We found that the time of hearing the bowel sounds (12.0-12.1 s) corresponded to the time of waveform change monitored by the sensor (12.036 s), and the sound tone magnitude corresponded to the waveform amplitude. This proves that the application of sensors to monitor bowel sounds is feasible, which opens up a new field for the application of graphene sensors and provides a new way for clinicians to judge the condition of the intestine.

Case Report: Simultaneous Ascending Aortic Dissection and Pulmonary Artery Dissection Combined by Aortopulmonary Fistula After Aortic Valve Replacement.

Aortopulmonary fistula with/without pulmonary artery dissection is an extremely rare and fatal complication of acute aortic dissection and is often discovered postmortem. We present a case with a simultaneous ascending aortic dissection and pulmonary artery dissection combined by aortopulmonary fistula after aortic valve surgery. However, the patient died of postoperative complications after surgery. Herein, the anatomical basis for this rare entity and its outcome is explored with an emphasis.

The mechanical property and corrosion resistance of Mg-Zn-Nd alloy fine wires in vitro and in vivo.

Titanium and its alloy are commonly used as surgical staples in the reconstruction of intestinal tract and stomach, however they cannot be absorbed in human body, which may cause a series of complications to influence further diagnosis. Magnesium and its alloy have great potential as surgical staples, because they can be degraded in human body and have good mechanical properties and biocompatibility. In this study, Mg-2Zn-0.5Nd (ZN20) alloy fine wires showed great potential as surgical staples. The ultimate tensile strength and elongation of ZN20 alloy fine wires were 248 MPa and 13%, respectively, which could be benefit for the deformation of the surgical staples from U-shape to B-shape. The bursting pressure of the wire was about 40 kPa, implying that it can supply sufficient mechanical support after anastomosis. Biochemical test and histological analysis illustrated good biocompatibility and biological safety of ZN20 alloy fine wire. The residual tensile stress formed on the outside of ZN20 fine wire during drawing would accelerate the corrosion. The second phase had a negative influence on corrosion property due to galvanic corrosion. The corrosion rate in vitro was faster than that in vivo due to the capsule formed on the surface of ZN20 alloy fine wire.

OPT3 is a component of the iron-signaling network between leaves and roots and misregulation of OPT3 leads to an over-accumulation of cadmium in seeds.

Plants and seeds are the main dietary sources of zinc, iron, manganese, and copper, but are also the main entry point for toxic elements such as cadmium into the food chain. We report here that an Arabidopsis oligopeptide transporter mutant, opt3-2, over-accumulates cadmium (Cd) in seeds and roots but, unexpectedly, under-accumulates Cd in leaves. The cadmium distribution in opt3-2 differs from iron, zinc, and manganese, suggesting a metal-specific mechanism for metal partitioning within the plant. The opt3-2 mutant constitutively up-regulates the Fe/Zn/Cd transporter IRT1 and FRO2 in roots, indicative of an iron-deficiency response. No genetic mutants that impair the shoot-to-root signaling of iron status in leaves have been identified. Interestingly, shoot-specific expression of OPT3 rescues the Cd sensitivity and complements the aberrant expression of IRT1 in opt3-2 roots, suggesting that OPT3 is required to relay the iron status from leaves to roots. OPT3 expression was found in the vasculature with preferential expression in the phloem at the plasma membrane. Using radioisotope experiments, we found that mobilization of Fe from leaves is severely affected in opt3-2, suggesting that Fe mobilization out of leaves is required for proper trace-metal homeostasis. When expressed in yeast, OPT3 does not localize to the plasma membrane, precluding the identification of the OPT3 substrate. Our in planta results show that OPT3 is important for leaf phloem-loading of iron and plays a key role regulating Fe, Zn, and Cd distribution within the plant. Furthermore, ferric chelate reductase activity analyses provide evidence that iron is not the sole signal transferred from leaves to roots in leaf iron status signaling.