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1.
J Orthop Surg Res ; 19(1): 324, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822361

ABSTRACT

BACKGROUND: The patellar height index is important; however, the measurement procedures are time-consuming and prone to significant variability among and within observers. We developed a deep learning-based automatic measurement system for the patellar height and evaluated its performance and generalization ability to accurately measure the patellar height index. METHODS: We developed a dataset containing 3,923 lateral knee X-ray images. Notably, all X-ray images were from three tertiary level A hospitals, and 2,341 cases were included in the analysis after screening. By manually labeling key points, the model was trained using the residual network (ResNet) and high-resolution network (HRNet) for human pose estimation architectures to measure the patellar height index. Various data enhancement techniques were used to enhance the robustness of the model. The root mean square error (RMSE), object keypoint similarity (OKS), and percentage of correct keypoint (PCK) metrics were used to evaluate the training results. In addition, we used the intraclass correlation coefficient (ICC) to assess the consistency between manual and automatic measurements. RESULTS: The HRNet model performed excellently in keypoint detection tasks by comparing different deep learning models. Furthermore, the pose_hrnet_w48 model was particularly outstanding in the RMSE, OKS, and PCK metrics, and the Insall-Salvati index (ISI) automatically calculated by this model was also highly consistent with the manual measurements (intraclass correlation coefficient [ICC], 0.809-0.885). This evidence demonstrates the accuracy and generalizability of this deep learning system in practical applications. CONCLUSION: We successfully developed a deep learning-based automatic measurement system for the patellar height. The system demonstrated accuracy comparable to that of experienced radiologists and a strong generalizability across different datasets. It provides an essential tool for assessing and treating knee diseases early and monitoring and rehabilitation after knee surgery. Due to the potential bias in the selection of datasets in this study, different datasets should be examined in the future to optimize the model so that it can be reliably applied in clinical practice. TRIAL REGISTRATION: The study was registered at the Medical Research Registration and Filing Information System (medicalresearch.org.cn) MR-61-23-013065. Date of registration: May 04, 2023 (retrospectively registered).


Subject(s)
Deep Learning , Patella , Humans , Patella/diagnostic imaging , Patella/anatomy & histology , Retrospective Studies , Male , Female , Automation , Radiography/methods , Middle Aged , Adult
2.
Article in English | MEDLINE | ID: mdl-38836956

ABSTRACT

PURPOSE: After robotic-assisted total knee arthroplasty (RA-TKA) surgery, some patients still experience joint discomfort. We aimed to establish an effective machine learning model that integrates radiomic features extracted from computed tomography (CT) scans and relevant clinical information to predict patient satisfaction three months postoperatively following RA-TKA. MATERIALS AND METHODS: After careful selection, data from 142 patients were randomly divided into a training set (n = 99) and a test set (n = 43), approximately in a 7:3 ratio. A total of 1329 radiomic features were extracted from the regions of interest delineated in CT scans. The features were standardized using normalization algorithms, and the least absolute shrinkage and selection operator regression model was employed to select radiomic features with ICC > 0.75 and P < 0.05, generating the Rad-score as feature markers. Univariate and multivariate logistic regression was then used to screen clinical information (age, body mass index, operation time, gender, surgical side, comorbidities, preoperative KSS score, preoperative range of motion (ROM), preoperative and postoperative HKA angle, preoperative and postoperative VAS score) as potential predictive factors. The satisfaction scale ≥ 20 indicates patient satisfaction. Finally, three prediction models were established, focusing on radiomic features, clinical features, and their fusion. Model performance was evaluated using Receiver Operating Characteristic curves and decision curve analysis. RESULTS: In the training set, the area under the curve (AUC) of the clinical model was 0.793 (95% CI 0.681-0.906), the radiomic model was 0.854 (95% CI 0.743-0.964), and the combined radiomic-clinical model was 0.899 (95% CI 0.804-0.995). In the test set, the AUC of the clinical model was 0.908 (95% CI 0.814-1.000), the radiomic model was 0.709 (95% CI 0.541-0.878), and the combined radiomic-clinical model was 0.928 (95% CI 0.842-1.000). The AUC of the radiomic-clinical model was significantly higher than the other two models. The decision curve analysis indicated its clinical application value. CONCLUSION: We developed a radiomic-based nomogram model using CT imaging to predict the satisfaction of RA-TKA patients at 3 months postoperatively. This model integrated clinical and radiomic features and demonstrated good predictive performance and excellent clinical application potential.

4.
Sci Adv ; 10(21): eadn4441, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38781334

ABSTRACT

Traditional cathode chemistry of Li-ion batteries relies on the transport of Li-ions within the solid structures, with the transition metal ions and anions acting as the static components. Here, we demonstrate that a solid solution of F- and PO43- facilitates the reversible conversion of a fine mixture of iron powder, LiF, and Li3PO4 into iron salts. Notably, in its fully lithiated state, we use commercial iron metal powder in this cathode, departing from electrodes that begin with iron salts, such as FeF3. Our results show that Fe-cations and anions of F- and PO43- act as charge carriers in addition to Li-ions during the conversion from iron metal to a solid solution of iron salts. This composite electrode delivers a reversible capacity of up to 368 mAh/g and a specific energy of 940 Wh/kg. Our study underscores the potential of amorphous composites comprising lithium salts as high-energy battery electrodes.

5.
Adv Mater ; : e2402324, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38696823

ABSTRACT

Rechargeable all-solid-state lithium metal batteries (ASSLMBs) utilizing inorganic solid-state electrolytes (SSEs) are promising for electric vehicles and large-scale grid energy storage. However, the Li dendrite growth in SSEs still constrains the practical utility of ASSLMBs. To achieve a high dendrite-suppression capability, SSEs must be chemically stable with Li, possess fast Li transfer kinetics, and exhibit high interface energy. Herein, a class of low-cost, eco-friendly, and sustainable oxyhalide-nitride solid electrolytes (ONSEs), denoted as LixNyIz-qLiOH (where x = 3y + z, 0 ≤ q ≤ 0.75), is designed to fulfill all the requirements. As-prepared ONSEs demonstrate chemically stable against Li and high interface energy (>43.08 meV Å-2), effectively restraining Li dendrite growth and the self-degradation at electrode interfaces. Furthermore, improved thermodynamic oxidation stability of ONSEs (>3 V vs Li+/Li, 0.45 V for pure Li3N), arising from the increased ionicity of Li─N bonds, contributes to the stability in ASSLMBs. As a proof-of-concept, the optimized ONSEs possess high ionic conductivity of 0.52 mS cm-1 and achieve long-term cycling of Li||Li symmetric cell for over 500 h. When coupled with the Li3InCl6 SSE for high-voltage cathodes, the bilayer oxyhalide-nitride/Li3InCl6 electrolyte imparts 90% capacity retention over 500 cycles for Li||1 mAh cm-2 LiCoO2 cells.

6.
J Vasc Surg ; 2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38621637

ABSTRACT

OBJECTIVE: As it remains unclear whether there are sex-based differences in clinical outcomes after thoracic endovascular aortic repair (TEVAR), this meta-analysis aimed to evaluate differences in early outcomes and overall survival between female and male patients who underwent TEVAR. METHODS: The PubMed, Embase, Web of Science, and Cochrane Central databases were searched for eligible studies published through June 10, 2023, that reported sex-based differences in clinical outcomes after TEVAR. The primary outcome was operative mortality; second outcomes included stroke, spinal cord ischemia, acute kidney injury, hospital length of stay, and overall survival. Patient characteristics, operative data, and early outcomes were aggregated using the random-effects model, presenting pooled risk ratio (RR) or standardized mean difference along with their corresponding 95% confidence intervals (CIs). Overall survival was assessed by reconstructing individual patient data to generate sex-specific pooled Kaplan-Meier curves. This study was registered in PROSPERO (CRD42023426069). RESULTS: Of the 1785 studies retrieved, 14 studies met all eligibility criteria, encompassing a total of 17,374 patients, comprising 5026 female and 12,348 male patients. Female patients were older, had a smaller maximum aortic diameter, had lower rates of smoking and coronary artery disease, and had higher rates of anemia. Intraoperatively, female patients were more likely to use iliac conduits and require blood transfusions. There were no sex-based differences in operative mortality (RR: 1.12, 95% CI: 0.90-1.40; P = .309), stroke (RR: 1.14, 95% CI: 0.95-1.38; P = .165), spinal cord ischemia (RR: 1.33, 95% CI: 0.83-2.14; P = .234), acute kidney injury (RR: 0.78, 95% CI: 0.52-1.17; P = .228), and hospital length of stay (standardized mean difference: 0.09, 95% CI: -0.03 to 0.20; P = .141). Pooled Kaplan-Meier estimates showed a worse overall survival in female patients compared with male patients (87.2% vs 89.8% at 2 years, log-rank P = .001). CONCLUSIONS: Among patients treated by TEVAR, female sex was not associated with increased risk of operative mortality or major morbidity. However, female patients exhibited a lower overall survival after TEVAR compared with male patients.

7.
Mol Biol Rep ; 51(1): 560, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38643284

ABSTRACT

BACKGROUND: Zygotic genome activation (ZGA) is an important event in the early embryo development, and human embryo developmental arrest has been highly correlated with ZGA failure in clinical studies. Although a few studies have linked maternal factors to mammalian ZGA, more studies are needed to fully elucidate the maternal factors that are involved in ZGA. METHODS AND RESULTS: In this study, we utilized published single-cell RNA sequencing data from a Dux-mediated mouse embryonic stem cell to induce a 2-cell-like transition state and selected potential drivers for the transition according to an RNA velocity analysis. CONCLUSIONS: An overlap of potential candidate markers of 2-cell-like-cells identified in this research with markers generated by various data sets suggests that Trim75 is a potential driver of minor ZGA and may recruit EP300 and establish H3K27ac in the gene body of minor ZGA genes, thereby contributing to mammalian preimplantation embryo development.


Subject(s)
Gene Expression Regulation, Developmental , Zygote , Animals , Humans , Mice , Embryo, Mammalian , Embryonic Development/genetics , Genome/genetics , Zygote/metabolism
8.
Opt Express ; 32(7): 12394-12404, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38571062

ABSTRACT

Since carbon dots (CDs) with good water solubility are preferred by researchers and biological applications, a hydrothermal method was used to synthesize green fluorescent CDs with an excitation-independent peak at 526 nm using deionized water as the solvent and neutral red as the carbon source. To achieve spectral modulation, the pH of the solvent was adjusted with KOH to obtain orange CDs (O-CDs) in an alkaline environment, with the emission peak red-shifted to 630 nm. The water-soluble CDs were prepared for multidimension sensing as Fe3+ sensing (on/off). Carbon dots dispersed into a silica gel matrix can be used for fingerprint detection of various materials.

9.
Plants (Basel) ; 13(6)2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38592925

ABSTRACT

Drought-induced stress poses a significant challenge to wheat throughout its growth, underscoring the importance of identifying drought-stable quantitative trait loci (QTLs) for enhancing grain yield. Here, we evaluated 18 yield-related agronomic and physiological traits, along with their drought tolerance indices, in a recombinant inbred line population derived from the XC7 × XC21 cross. These evaluations were conducted under both non-stress and drought-stress conditions. Drought stress significantly reduced grain weight per spike and grain yield per plot. Genotyping the recombinant inbred line population using the wheat 90K single nucleotide polymorphism array resulted in the identification of 131 QTLs associated with the 18 traits. Drought stress also exerted negative impacts on grain formation and filling, directly leading to reductions in grain weight per spike and grain yield per plot. Among the identified QTLs, 43 were specifically associated with drought tolerance across the 18 traits, with 6 showing direct linkages to drought tolerance in wheat. These results provide valuable insights into the genetic mechanisms governing wheat growth and development, as well as the traits contributing to the drought tolerance index. Moreover, they serve as a theoretical foundation for the development of new wheat cultivars having exceptional drought tolerance and high yield potentials under both drought-prone and drought-free conditions.

11.
J Anesth ; 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38581580

ABSTRACT

PURPOSE: Present study was designed to investigate the association between muscular tissue desaturation and acute kidney injury (AKI) in older patients undergoing major abdominal surgery. METHOD: A total of 253 patients (≥ 65 years old) who underwent abdominal surgery with expected duration ≥ 2 h were enrolled. Muscular tissue oxygen saturation (SmtO2) was monitored at quadriceps and bilateral flanks during surgery. Muscular desaturation was defined as SmtO2 < 90% baseline lasting for > 60 s. The primary outcome was the incidence of AKI within postoperative 7 days. The association between muscular desaturation and AKI was analyzed by multivariable logistic regression model. The secondary outcomes indicated the other complications within postoperative 30 days. RESULTS: Among 236 patients, 44 (18.6%) of them developed AKI. The incidence of muscular desaturation at quadriceps was 28.8% (68/236). Patients with muscular desaturation had higher incidence of AKI than those without desaturation (27.9% [19/68], vs. 14.9% [25/168], P = 0.020). After adjustment of confounders, multivariable analysis showed that muscular desaturation at quadriceps was significantly associated with an increased risk of AKI (OR = 2.84, 95% CI 1.21-6.67, P = 0.016). Muscular desaturations at left and right flank were also associated with an increased risk of AKI (OR = 6.38, 95% CI 1.78-22.89, P = 0.004; OR = 8.90, 95% CI 1.42-45.63; P = 0.019, respectively). Furthermore, patients with muscular desaturation may have a higher risk of pulmonary complications, sepsis and stroke at 30-day follow-up. CONCLUSION: Muscular desaturation was associated with postoperative AKI in older patients undergoing major abdominal surgery which may serve as a predictor of AKI.

12.
Nat Chem ; 16(6): 922-929, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38570729

ABSTRACT

Lithium metal batteries represent a promising technology for next-generation energy storage, but they still suffer from poor cycle life due to lithium dendrite formation and cathode cracking. Fluorinated solvents can improve battery longevity by improving LiF content in the solid-electrolyte interphase; however, the high cost and environmental concerns of fluorinated solvents limit battery viability. Here we designed a series of fluorine-free solvents through the methylation of 1,2-dimethoxyethane, which promotes inorganic LiF-rich interphase formation through anion reduction and achieves high oxidation stability. The anion-derived LiF interphases suppress lithium dendrite growth on the lithium anode and minimize cathode cracking under high-voltage operation. The Li+-solvent structure is investigated through in situ techniques and simulations to draw correlations between the interphase compositions and electrochemical performances. The methylation strategy provides an alternative pathway for electrolyte engineering towards high-voltage electrolytes while reducing dependence on expensive fluorinated solvents.

13.
Int J Surg ; 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38445500

ABSTRACT

BACKGROUND: Ticagrelor is reportedly more effective than clopidogrel in preventing atherothrombotic events in patients with percutaneous coronary intervention. However, the optimal antiplatelet therapy strategy after off-pump coronary artery bypass grafting (OPCABG) is yet to be established. MATERIALS AND METHODS: This study was performed using the prospectively-maintained database at our institution. Patients who underwent OPCABG were divided into the clopidogrel and the ticagrelor groups. Propensity score matching analysis was performed between the two groups. The clinical outcome was the occurrence of major adverse cardiovascular event (MACE), defined as a composite of vascular death, myocardial infarction, or stroke 1 year after surgery. RESULTS: In total, 545 patients completed the entire follow-up assessment. After propensity score matching, 232 patients each were included in the clopidogrel and ticagrelor groups. The primary outcome occurred in 7.8% and 4.3% of patients in the clopidogrel and ticagrelor groups, respectively (P=0.113). CYP2C19 variants (*2, *3, and *17) did not impact the clinical outcomes, regardless of the use of clopidogrel or ticagrelor. The rates of MACE were significantly lower in patients carrying the ABCB1 C3435T CT/TT genotypes in the ticagrelor group than in those carrying the ABCB1 C3435T CC genotype in the clopidogrel group (1.4% vs. 9.1%, adjusted P=0.030), as well as those carrying the ABCB1 C3435T CC genotype in the ticagrelor group (1.4% vs. 8.9%, adjusted P=0.036). The ABCB1 C3435T CC genotype was significantly associated with the incidence of 1-year MACE (HR=1.558, 95% CI 1.109-2.188, P=0.011). Patients who experienced severe perioperative bleeding exhibited a significantly higher incidence of MACE than those who did not experience severe perioperative bleeding (14.0% vs. 4.9%, adjusted P=0.007). CONCLUSION: There was no significant difference in the 1-year MACE between patients receiving clopidogrel and those receiving ticagrelor after OPCABG. Notably, The ABCB1 C3435T CC genotype was related to a higher risk of MACE.

14.
J Hazard Mater ; 469: 133956, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38460258

ABSTRACT

Polyhalogenated carbazoles (PHCZs), an emerging persistent halogenated organic pollutant, have been detected in the environment. However, our understanding of PHCZs in the ocean remains limited. In this study, 47 seawater samples (covering 50 - 4000 m) and sediment samples (49 surface and 3 cores) were collected to investigate the occurrence and spatial distribution patterns of carbazole and its halogenated derivants (CZDs) in the Western Pacific Ocean. In seawater, the detection frequencies of CZ (97.87%) and 3-CCZ (57.45%) were relatively high. In addition, the average concentration of ΣPHCZs in the upper water (< 150 m, 0.23 ± 0.21 ng/L) was significantly lower than that in the deep ocean (1000 - 4000 m, 0.65 ± 0.56 ng/L, P < 0.05), which may indicate the vertical transport of PHCZs in the marine environment. The concentration of ΣCZDs in surface sediment ranges from 0.46 to 6.48 ng/g (mean 1.54 ng/g), among which CZ and 36-CCZ were the predominant components. Results from sediment cores demonstrate a noteworthy negative correlation between the concentration of CZDs and depth, indicating the ongoing natural degradation process occurring in sediment cores over a long period. This study offers distinctive insights into the occurrence, composition, and vertical features of CZDs in oceanic environments.

16.
Chem Rev ; 124(6): 3494-3589, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38478597

ABSTRACT

The renewable energy industry demands rechargeable batteries that can be manufactured at low cost using abundant resources while offering high energy density, good safety, wide operating temperature windows, and long lifespans. Utilizing fluorine chemistry to redesign battery configurations/components is considered a critical strategy to fulfill these requirements due to the natural abundance, robust bond strength, and extraordinary electronegativity of fluorine and the high free energy of fluoride formation, which enables the fluorinated components with cost effectiveness, nonflammability, and intrinsic stability. In particular, fluorinated materials and electrode|electrolyte interphases have been demonstrated to significantly affect reaction reversibility/kinetics, safety, and temperature tolerance of rechargeable batteries. However, the underlining principles governing material design and the mechanistic insights of interphases at the atomic level have been largely overlooked. This review covers a wide range of topics from the exploration of fluorine-containing electrodes, fluorinated electrolyte constituents, and other fluorinated battery components for metal-ion shuttle batteries to constructing fluoride-ion batteries, dual-ion batteries, and other new chemistries. In doing so, this review aims to provide a comprehensive understanding of the structure-property interactions, the features of fluorinated interphases, and cutting-edge techniques for elucidating the role of fluorine chemistry in rechargeable batteries. Further, we present current challenges and promising strategies for employing fluorine chemistry, aiming to advance the electrochemical performance, wide temperature operation, and safety attributes of rechargeable batteries.

17.
Nature ; 627(8002): 101-107, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38418886

ABSTRACT

Li-ion batteries (LIBs) for electric vehicles and aviation demand high energy density, fast charging and a wide operating temperature range, which are virtually impossible because they require electrolytes to simultaneously have high ionic conductivity, low solvation energy and low melting point and form an anion-derived inorganic interphase1-5. Here we report guidelines for designing such electrolytes by using small-sized solvents with low solvation energy. The tiny solvent in the secondary solvation sheath pulls out the Li+ in the primary solvation sheath to form a fast ion-conduction ligand channel to enhance Li+ transport, while the small-sized solvent with low solvation energy also allows the anion to enter the first Li+ solvation shell to form an inorganic-rich interphase. The electrolyte-design concept is demonstrated by using fluoroacetonitrile (FAN) solvent. The electrolyte of 1.3 M lithium bis(fluorosulfonyl)imide (LiFSI) in FAN exhibits ultrahigh ionic conductivity of 40.3 mS cm-1 at 25 °C and 11.9 mS cm-1 even at -70 °C, thus enabling 4.5-V graphite||LiNi0.8Mn0.1Co0.1O2 pouch cells (1.2 Ah, 2.85 mAh cm-2) to achieve high reversibility (0.62 Ah) when the cells are charged and discharged even at -65 °C. The electrolyte with small-sized solvents enables LIBs to simultaneously achieve high energy density, fast charging and a wide operating temperature range, which is unattainable for the current electrolyte design but is highly desired for extreme LIBs. This mechanism is generalizable and can be expanded to other metal-ion battery electrolytes.

18.
Nat Commun ; 15(1): 1206, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38332019

ABSTRACT

Micro-sized silicon anodes can significantly increase the energy density of lithium-ion batteries with low cost. However, the large silicon volume changes during cycling cause cracks for both organic-inorganic interphases and silicon particles. The liquid electrolytes further penetrate the cracked silicon particles and reform the interphases, resulting in huge electrode swelling and quick capacity decay. Here we resolve these challenges by designing a high-voltage electrolyte that forms silicon-phobic interphases with weak bonding to lithium-silicon alloys. The designed electrolyte enables micro-sized silicon anodes (5 µm, 4.1 mAh cm-2) to achieve a Coulombic efficiency of 99.8% and capacity of 2175 mAh g-1 for >250 cycles and enable 100 mAh LiNi0.8Co0.15Al0.05O2 pouch full cells to deliver a high capacity of 172 mAh g-1 for 120 cycles with Coulombic efficiency of >99.9%. The high-voltage electrolytes that are capable of forming silicon-phobic interphases pave new ways for the commercialization of lithium-ion batteries using micro-sized silicon anodes.

19.
Nat Commun ; 15(1): 575, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38233408

ABSTRACT

Aqueous sodium-ion batteries are practically promising for large-scale energy storage, however energy density and lifespan are limited by water decomposition. Current methods to boost water stability include, expensive fluorine-containing salts to create a solid electrolyte interface and addition of potentially-flammable co-solvents to the electrolyte to reduce water activity. However, these methods significantly increase costs and safety risks. Shifting electrolytes from near neutrality to alkalinity can suppress hydrogen evolution while also initiating oxygen evolution and cathode dissolution. Here, we present an alkaline-type aqueous sodium-ion batteries with Mn-based Prussian blue analogue cathode that exhibits a lifespan of 13,000 cycles at 10 C and high energy density of 88.9 Wh kg-1 at 0.5 C. This is achieved by building a nickel/carbon layer to induce a H3O+-rich local environment near the cathode surface, thereby suppressing oxygen evolution. Concurrently Ni atoms are in-situ embedded into the cathode to boost the durability of batteries.

20.
J Neuroinflammation ; 21(1): 27, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38243316

ABSTRACT

BACKGROUND: Sympathoexcitation contributes to myocardial remodeling in heart failure (HF). Increased circulating pro-inflammatory mediators directly act on the Subfornical organ (SFO), the cardiovascular autonomic center, to increase sympathetic outflow. Circulating mitochondria (C-Mito) are the novel discovered mediators for inter-organ communication. Cyclic GMP-AMP synthase (cGAS) is the pro-inflammatory sensor of damaged mitochondria. OBJECTIVES: This study aimed to assess the sympathoexcitation effect of C-Mito in HF mice via promoting endothelial cGAS-derived neuroinflammation in the SFO. METHODS: C-Mito were isolated from HF mice established by isoprenaline (0.0125 mg/kg) infusion via osmotic mini-pumps for 2 weeks. Structural and functional analyses of C-Mito were conducted. Pre-stained C-Mito were intravenously injected every day for 2 weeks. Specific cGAS knockdown (cGAS KD) in the SFO endothelial cells (ECs) was achieved via the administration of AAV9-TIE-shRNA (cGAS) into the SFO. The activation of cGAS in the SFO ECs was assessed. The expression of the mitochondrial redox regulator Dihydroorotate dehydrogenase (DHODH) and its interaction with cGAS were also explored. Neuroinflammation and neuronal activation in the SFO were evaluated. Sympathetic activity, myocardial remodeling, and cardiac systolic dysfunction were measured. RESULTS: C-Mito were successfully isolated, which showed typical structural characteristics of mitochondria with double-membrane and inner crista. Further analysis showed impaired respiratory complexes activities of C-Mito from HF mice (C-MitoHF) accompanied by oxidative damage. C-Mito entered ECs, instead of glial cells and neurons in the SFO of HF mice. C-MitoHF increased the level of ROS and cytosolic free double-strand DNA (dsDNA), and activated cGAS in cultured brain endothelial cells. Furthermore, C-MitoHF highly expressed DHODH, which interacted with cGAS to facilitate endothelial cGAS activation. C-MitoHF aggravated endothelial inflammation, microglial/astroglial activation, and neuronal sensitization in the SFO of HF mice, which could be ameliorated by cGAS KD in the ECs of the SFO. Further analysis showed C-MitoHF failed to exacerbate sympathoexcitation and myocardial sympathetic hyperinnervation in cGAS KD HF mice. C-MitoHF promoted myocardial fibrosis and hypertrophy, and cardiac systolic dysfunction in HF mice, which could be ameliorated by cGAS KD. CONCLUSION: Collectively, we demonstrated that damaged C-MitoHF highly expressed DHODH, which promoted endothelial cGAS activation in the SFO, hence aggravating the sympathoexcitation and myocardial injury in HF mice, suggesting that C-Mito might be the novel therapeutic target for sympathoexcitation in HF.


Subject(s)
Heart Failure , Subfornical Organ , Mice , Animals , Endothelial Cells/metabolism , Neuroinflammatory Diseases , Dihydroorotate Dehydrogenase , Nucleotidyltransferases/metabolism , Mitochondria/metabolism
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