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1.
Artigo em Inglês | MEDLINE | ID: mdl-37149411

RESUMO

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a key pathogen associated with ventilator-associated pneumonia (VAP). Research on treatment outcomes, especially ventilator dependence, in patients with VAP caused by CRAB remains limited. METHODS: This retrospective multicenter study included ICU-admitted patients with VAP caused by CRAB. The original cohort was included as the mortality evaluation cohort. The ventilator dependence evaluation cohort included cases that survived more than 21 days after VAP and without prolonged ventilation before VAP onset. The mortality rate, ventilator dependence rate, clinical factors associated with treatment outcomes, and treatment outcome differences with various VAP onset times were investigated. RESULTS: In total, 401 patients with VAP caused by CRAB were analyzed. The 21-day all-cause mortality rate was 25.2%, and the 21-day ventilator dependence rate was 48.8%. Clinical factors associated with 21-day mortality included lower body mass index, higher sequential organ failure assessment score, vasopressors usage, CRAB persistence, and VAP onset time > seven days. Clinical factors associated with 21-day ventilator dependence included older age, vasopressors usage, and VAP onset time > seven days. CONCLUSIONS: ICU-admitted patients with CRAB-related VAP had high mortality and ventilator dependence rates. Older age, vasopressor usage, and longer VAP onset time were independent factors associated with ventilator dependence.

2.
Ultrasound Med Biol ; 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37137743

RESUMO

OBJECTIVES: The application of deep learning to medical image segmentation has received considerable attention. Nevertheless, when segmenting thyroid ultrasound images, it is difficult to achieve good segmentation results using deep learning methods because of the large number of nonthyroidal regions and insufficient training data. METHODS: In this study, a Super-pixel U-Net, designed by adding a supplementary path to U-Net, was devised to boost the segmentation results of thyroids. The improved network can introduce more information into the network, boosting auxiliary segmentation results. A multi-stage modification is introduced in this method, which includes boundary segmentation, boundary repair, and auxiliary segmentation. To reduce the negative effects of non-thyroid regions in the segmentation, U-Net was utilized to obtain rough boundary outputs. Subsequently, another U-Net is trained to improve and repair the coverage of the boundary outputs. Super-pixel U-Net was applied in the third stage to assist in the segmentation of the thyroid more precisely. Finally, multidimensional indicators were used to compare the segmentation results of the proposed method with those of other comparison experiments. DISCUSSION: The proposed method achieved an F1 Score of 0.9161 and an IoU of 0.9279. Furthermore, the proposed method also exhibits better performance in terms of shape similarity, with an average convexity of 0.9395. an average ratio of 0.9109, an average compactness of 0.8976, an average eccentricity of 0.9448, and an average rectangularity of 0.9289. The average area estimation indicator was 0.8857. CONCLUSION: The proposed method exhibited superior performance, proving the improvements of the multi-stage modification and Super-pixel U-Net.

3.
JASA Express Lett ; 3(5)2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37125871

RESUMO

Spectral weights in octave-frequency bands from 0.25 to 4 kHz were estimated for speech-in-noise recognition using two sentence materials (i.e., the IEEE and AzBio sentences). The masking noise was either unmodulated or sinusoidally amplitude-modulated at 8 Hz. The estimated spectral weights did not vary significantly across two test sessions and were similar for the two sentence materials. Amplitude-modulating the masker increased the weight at 2 kHz and decreased the weight at 0.25 kHz, which may support an upward shift in spectral weights for temporally fluctuating maskers.


Assuntos
Mascaramento Perceptivo , Percepção da Fala , Ruído , Reconhecimento Psicológico , Idioma
4.
Int J Biol Macromol ; 242(Pt 1): 124767, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37164134

RESUMO

As the demand for botanical food additives and eco-friendly food packaging materials grows, the use of essential oils, edible biodegradable films and coatings are becoming more popular in packaging. In this review, we discussed the recent research trends in the use of natural essential oils, as well as polysaccharide-based coatings and films: from the composition of the substrates to preparing formulations for the production of film-forming technologies. Our review emphasized the functional properties of polysaccharide-based edible films that contain plant essential oils. The interactions between essential oils and other ingredients in edible films and coatings including polysaccharides, lipids, and proteins were discussed along with effects on film physical properties, essential oil release, their active role in meat preservation. We presented the opportunities and challenges related to edible films and coatings including essential oils to increase their industrial value and inform the development of edible biodegradable packaging, bio-based functional materials, and innovative food preservation technologies.

5.
BMC Plant Biol ; 23(1): 242, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37150815

RESUMO

BACKGROUND: Ophiopogon japonicus, mainly planted in Sichuan (CMD) and Zhejiang (ZMD) province in China, has a lengthy cultivation history. During the long period of domestication, the genetic diversity of cultivated O. japonicus has substantially declined, which will affect the population continuity and evolutionary potential of this species. Therefore, it is necessary to clarify the phylogeography of cultivated O. japonicus to establish a theoretical basis for the utilization and conservation of the genetic resources of O. japonicus. RESULT: The genetic diversity and population structure of 266 O. japonicus individual plants from 23 sampling sites were analyzed based on 4 chloroplast DNA sequences (atpB-rbcL, rpl16, psbA-trnH and rpl20-5'rps12) to identify the effects of domestication on genetic diversity of cultivars and determine their geographic origins. The results showed that cultivated O. japonicus and wild O. japonicus had 4 and 15 haplotypes respectively. The genetic diversity of two cultivars (Hd = 0.35700, π = 0.06667) was much lower than that of the wild populations (Hd = 0.76200, π = 0.20378), and the level of genetic diversity in CMD (Hd = 0.01900, π = 0.00125) was lower than that in ZMD (Hd = 0.06900, π = 0.01096). There was significant difference in genetic differentiation between the cultivated and the wild (FST = 0.82044), especially between the two cultivars (FST = 0.98254). This species showed a pronounced phylogeographical structure (NST > GST, P < 0.05). The phylogenetic tree showed that the genetic difference between CMD and ZMD was not enough to distinguish the cultivars between the two producing areas by using O. amblyphyllus Wang et Dai as an outgroup. In addition, both CMD and ZMD have a closer relationship with wild populations in Sichuan than that in Zhejiang. The results of the TCS network and species distribution model suggested that the wild population TQ located in Sichuan province could serve as the ancestor of cultivated O. japonicus, which was supported by RASP analysis. CONCLUSION: These results suggest that cultivated O. japonicus has experienced dramatic loss of genetic diversity under anthropogenic influence. The genetic differentiation between CMD and ZMD is likely to be influenced by founder effect and strong artificial selection for plant traits. It appears that wild populations in Sichuan area are involved in the origin of not only CMD but also ZMD. In addition, we also raise some suggestions for planning scientific strategies for resource conservation of O. japonicus based on its genetic diversity and population structure.


Assuntos
DNA de Cloroplastos , Ophiopogon , DNA de Cloroplastos/genética , Filogeografia , Filogenia , Ophiopogon/química , Ophiopogon/genética , Haplótipos/genética , Variação Genética
6.
Artigo em Inglês | MEDLINE | ID: mdl-37162672

RESUMO

In order to preliminarily explore the distribution of antibiotic pollution in the coastal waters of eastern China, the concentrations of 13 antibiotics in 5 representative coastal rivers in Jiangsu and 21 sampling sites in the coastal waters of Jiangsu were analyzed. The total antibiotic concentrations in the 5 rivers ranged from 33.14 to 417.78 ng L-1, and the total antibiotic concentrations in the 21 sampling sites ranged from 0.90 to 86.33 ng L-1. Macrolides exhibited the highest total concentration and the maximum detection frequency in both coastal rivers and the coastal waters. The concentrations of antibiotics in a sampling site decreased as the distance of the sampling site from the coastline increased, indicating that river inputs are important sources of antibiotic pollution in the coastal waters of Jiangsu. The detection frequencies of roxithromycin, lincomycin, azithromycin, and sulfamethoxazole in the rivers and sampling sites were above 70%. Correlation analysis showed that the concentrations of antibiotics were positively correlated with the levels of chemical oxygen demand, total phosphorus, and total nitrogen. Risk assessments revealed that roxithromycin and ofloxacin posed medium ecological and resistance risks, respectively, to the most sensitive aquatic organisms in the coastal waters of Jiangsu. The results of this study highlight the significance of monitoring and controlling the concentrations of antibiotic contaminants in the coastal waters of Jiangsu.

9.
Chem Commun (Camb) ; 59(42): 6314-6334, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37132271

RESUMO

Recently, the increasing concerns regarding environmental and energy-related issues due to the use of fossil fuels have triggered extensive research on sustainable electrochemical energy storage and conversion (EESC). In this case, covalent triazine frameworks (CTFs) possess a large surface area, tailorable conjugated structures, electron donating-accepting/conducting moieties, and excellent chemical and thermal stabilities. These merits make them leading candidates for EESC. However, their poor electrical conductivity impedes electron and ion conduction, leading to unsatisfactory electrochemical performances, which limit their commercial applications. Thus, to overcome these challenges, CTF-based nanocomposites and their derivatives such as heteroatom-doped porous carbons, which inherit most of the merits of pristine CTFs, lead to excellent performances in the field of EESC. In this review, initially, we briefly highlight the existing strategies for the synthesis of CTFs with application-targeted properties. Next, we review the contemporary progress of CTFs and their derivatives related to electrochemical energy storage (supercapacitors, alkali-ion batteries, lithium-sulfur batteries, etc.) and conversion (oxygen reduction/evolution reaction, hydrogen evolution reaction, carbon dioxide reduction reaction, etc.). Finally, we discuss perspectives on current challenges and recommendations for the further development of CTF-based nanomaterials in burgeoning EESC research.

10.
Environ Pollut ; : 121880, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37236590

RESUMO

Triphenyl phosphate (TPhP) is a typical aromatic-based non-chlorinated organophosphorus flame retardant, which has been widely detected in a variety of environments and poses high environmental and human health risks. In this study, biochar coated nano-zero-valent iron (nZVI) was fabricated to activate persulfate (PS) to degrade TPhP from water. A range of biochars (BC400, BC500, BC600, BC700, and BC800) was prepared as potential support to coat nZVI by pyrolyzing corn stalk at 400, 500, 600, 700 and 800 °C. As outperformed other biochars in adsorption rate, adsorption capacity, and less reluctant to be influenced by environmental factors (pH, humic acid (HA), coexistence of anions), BC800 was to act as support to coat nZVI (labeled as BC800@nZVI). SEM, TEM, XRD and XPS characterization showed that nZVI was successfully supported on the BC800. Removal efficiency of 10 mg L-1 TPhP by BC800@nZVI/PS could reach to 96.9% with a high catalytic degradation kinetic rate of 0.0484 min-1 under optimal condition. The removal efficiency remained stable in a wide pH range (3-9) and moderate concentration of HA and coexistence of anions, demonstrated the promising of using BC800@nZVI/PS system to eliminate TPhP contamination. Results from the radical scavenging and electron paramagnetic resonance (EPR) experiments demonstrated radical pathway (i.e. SO4·- and HO·) and non-radical pathway via 1O2 both play important role in TPhP degradation. The TPhP degradation pathway was proposed based on the six degradation intermediates analyzed by LC-MS. This study illustrated the synergistic mechanism of adsorption and catalytic oxidation removal of TPhP by BC800@nZVI/PS system, and provided a cost-efficient approach for TPhP remediation.

11.
Neurosci Lett ; 809: 137300, 2023 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-37187340

RESUMO

Studies have indicated that neuronal mitochondrial injury may be involved in the brain injury caused by intracerebral hemorrhage (ICH). Syntaphilin (SNPH) is associated with mitochondrial anchoring and Armadillo repeat-containing X-linked protein 1 (Armcx1) is linked to mitochondrial transport. This study aimed to analyze the contribution of SNPH and Armcx1 to the neuronal damage resulting from ICH. Primary cultured neuron cells were exposed to oxygenated hemoglobin to replicate the effects of ICH stimulation, while a mouse model of ICH was established by injecting autoblood into the basal ganglia. Specific SNPH knockout or Armcx1 overexpression in neurons is achieved by stereolocalization injection of adeno-associated virus vectors carrying hsyn specific promoters. First, it was confirmed that there is a correlation between SNPH/Armcx1 and ICH pathology, as evidenced by the rise of SNPH and the decrease of Armcx1 in neurons exposed to ICH both in vitro and in vivo. Second, our research revealed the protective effects of SNPH knockdown and Armcx1 overexpression on brain cell death around the hematoma in mice. In addition, the efficacy of SNPH knockdown and Armcx1 overexpression in improving neurobehavioral deficits was also demonstrated in mouse ICH model. Thus, moderate adjusting the levels of SNPH and Armcx1 may be an effective way to improve the outcome of ICH.

12.
Eur Surg Res ; : 1, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37231813

RESUMO

INTRODUCTION: This research aims to explore the expression levels of microRNA (miR)-300/BCL2L11 and their values in the clinical diagnosis of papillary thyroid cancer (PTC). METHODS: Pathological tissues that were surgically removed for thyroid disease were selected. miR-300 and BCL2L11 expression levels in the samples were measured. ROC curves were plotted to analyze miR-300 and BCL2L11 predictive values for PTC. Upon silencing miR-300 and Silencing BCL2L11 in PTC cells, the corresponding miR-300 and BCL2L11 expression levels were tested, followed by examining PTC cell activities. The targeting relationship of miR-300 and BCL2L11 was detected by the bioinformatics website and luciferase activity assay. RESULTS: miR-300 expression levels were elevated and BCL2L11 expression levels were reduced in PTC tissues. miR-300 and BCL2L11 expression levels in PTC tissues had a correlation with TNM stage and lymph node metastasis. The results of ROC curve revealed that both miR-300 and BCL2L11 had clinical predictive values for PTC. Mechanistically, miR-300 negatively regulated BCL2L11. The functional assays unveiled that silencing miR-300 impeded PTC cell activities, and silencing BCL2L11 induced PTC cell activities. In the rescue experiment, silencing BCL2L11 reversed the impacts of silencing miR-300 on PTC cell development. CONCLUSION: This study underlines that miR-300 expression is increased and BCL2L11 expression is declined in PTC. miR-300 and BCL2L11 both have clinical predictive values for diagnosing PTC.

13.
Sci Total Environ ; : 164355, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37245828

RESUMO

Black carbon (BC) is the strongest light-absorbing aerosol in the atmosphere. The coating process causes lensing effects to enhance the BC absorption. The reported BC absorption enhancement values (Eabs) significantly differ partly due to the measurement methods used. The biggest difficulty in measuring the Eabs values is how to denude the coated particles so that the true value of absorption without coatings can be distinguished from lensing effects. In this study, we proposed a new approach based on an integrating sphere (IS) system plus in-situ absorption monitoring instrument to study Eabs in ambient aerosols. This approach is capable of (i) "de-lensing through solvent dissolution and solvent de-refraction", by which the absorption coefficient of denuded BC is acquired, and (ii) monitoring in-situ absorption with photoacoustic spectroscopy. With the help of the EC concentration measured by a thermal/optical carbon analyser, the Eabs values were calculated as the quotient of in-situ mass absorption efficiency divided by denude mass absorption efficiency. We applied this new approach to measure the Eabs values of four seasons in Beijing and found an annual mean of 1.90 ±â€¯0.41 in 2019. More importantly, a previous assumption that BC absorption efficiency may be progressively enhanced by increased air pollution was validated and quantified using a logarithmic relationship of Eabs = 0.6 ln (PM2.5 ̶ 3.59) ̶ 0.43 (R2 = 0.99). This signals a continued drop of Eabs for future ambient aerosols with the sustained improvement in local air quality in China, meriting serious attention to its influences in climate, air quality, and atmospheric chemistry.

14.
Microbiol Spectr ; : e0429722, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37093040

RESUMO

Here, we aimed to compare the effects of different preservation methods on outcomes of fecal microbiota. We evaluated the effects of different preservation methods using stool sample preservation experiments for up to 1 year. The stool samples from feces of healthy volunteers were grouped based on whether absolute ethanol was added and whether they were hypothermically preserved. Besides, we performed a systematic review to combine current fecal microbiota preservation evidence. We found that Proteobacteria changed significantly and Veillonellaceae decreased significantly in the 12th month in the room temperature + absolute ethanol group. The four cryopreservation groups have more similarities with fresh sample in the 12 months; however, different cryopreservation methods have different effects on several phyla, families, and genera. A systematic review showed that the Shannon diversity and Simpson index of samples stored in RNAlater for 1 month were not statistically significant compared with those stored immediately at -80°C (P = 0.220 and P = 0.123, respectively). The -80°C refrigerator and liquid nitrogen cryopreservation with 10% glycerine can both maintain stable microbiota of stool samples for long-term preservation. The addition of absolute ethanol to cryopreserved samples had no significant difference in the effect of preserving fecal microbial characteristics. Our study provides empirical insights into preservation details for future studies of the long-term preservation of fecal microbiota. Systematic review and meta-analysis found that the gut microbiota structure, composition, and diversity of samples preserved by storage methods, such as preservation solution, are relatively stable, which were suitable for short-term storage at room temperature. IMPORTANCE The study of gut bacteria has become increasingly popular, and fecal sample preservation methods and times need to be standardized. Here, we detail a 12-month study of fecal sample preservation, and our study provides an empirical reference about experimental details for long-term high-quality storage of fecal samples in the field of gut microbiology research. The results showed that the combination of -80°C/liquid nitrogen deep cryopreservation and 10% glycerol was the most effective method for the preservation of stool samples, which is suitable for long-term storage for at least 12 months. The addition of anhydrous ethanol to the deep cryopreserved samples did not make a significant difference in the preservation of fecal microbiological characteristics. Combined with the results of systematic reviews and meta-analyses, we believe that, when researchers preserve fecal specimens, it is essential to select the proper preservation method and time period in accordance with the goal of the study.

15.
Mar Environ Res ; 188: 105992, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37094527

RESUMO

Offshore areas are particularly important in recognizing microplastics pollution because they are sinks of land imports and sources of ocean microplastics. This study investigated the pollution and distribution of microplastics in the offshore Sea, rivers and wastewater treatment plants (WWTPs) in Jiangsu coastal area in China. Results showed that microplastics were widely present in the offshore area, with an average abundance of 3.1-3.5 items/m3. Significantly higher abundance was present in rivers (3.7-5.9 item/m3), municipal WWTPs (13.7 ± 0.5 item/m3), and industrial WWTPs (19.7 ± 1.2 item/m3). The proportion of small-sized microplastics (1-3 mm) increased from WWTPs (53%) to rivers (64%) and the offshore area (53%). Polyamide (PA), polyethylene (PE), polyvinyl chloride (PVC), polypropylene (PP), polystyrene (PS), and rayon (RA) were dominant types of microplastics. Both living and industrial sources contributed to the prevalent microplastics in the offshore Sea. Redundancy analysis showed that small-sized microplastics (1-3 mm) were positively correlated to total phosphorus (TP), while large-sized microplastics (3-5 mm) were positively correlated to TP and NH3-N. The abundance of PE, PP and PVC microplastics were positively correlated to TP and total nitrogen (TN), thus nutrients could be indicators of microplastics pollution in the offshore area.

16.
Nat Commun ; 14(1): 2093, 2023 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-37055385

RESUMO

Thrombocytopenia is a major complication in a subset of patients with multiple myeloma (MM). However, little is known about its development and significance during MM. Here, we show thrombocytopenia is linked to poor prognosis in MM. In addition, we identify serine, which is released from MM cells into the bone marrow microenvironment, as a key metabolic factor that suppresses megakaryopoiesis and thrombopoiesis. The impact of excessive serine on thrombocytopenia is mainly mediated through the suppression of megakaryocyte (MK) differentiation. Extrinsic serine is transported into MKs through SLC38A1 and downregulates SVIL via SAM-mediated tri-methylation of H3K9, ultimately leading to the impairment of megakaryopoiesis. Inhibition of serine utilization or treatment with TPO enhances megakaryopoiesis and thrombopoiesis and suppresses MM progression. Together, we identify serine as a key metabolic regulator of thrombocytopenia, unveil molecular mechanisms governing MM progression, and provide potential therapeutic strategies for treating MM patients by targeting thrombocytopenia.


Assuntos
Mieloma Múltiplo , Trombocitopenia , Humanos , Medula Óssea/metabolismo , Trombopoese/fisiologia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/metabolismo , Trombocitopenia/metabolismo , Células da Medula Óssea/metabolismo , Megacariócitos , Plaquetas/metabolismo , Microambiente Tumoral
17.
Environ Pollut ; 328: 121600, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37068649

RESUMO

Antimony (Sb) in PM2.5 has attracted close attention as a new air pollutant due to its extensive use in daily life. The identification of antimony sources in PM2.5 by scientific methods is important to control its pollution. In this study, the Sb and other elements concentrations and Pb isotopic compositions in PM2.5 and possible pollution sources (soil, road dust, traffic emission, coal-fired fly ash, local factory emission dust and cement dust) were analyzed. The results showed that the Sb in the PM2.5 samples had seasonal change. The enrichment factors of Sb in PM2.5 samples were all above 100 in four seasons, which indicated anthropogenic pollution. The average value of potential ecological risk index was at extremely high-risk level greater than 320. Based on Pearson correlation coefficient and hierarchical cluster analysis results, the pollution sources of antimony and lead in PM2.5 samples were highly consistent which means that Pb isotopes might be a new and feasible tracer for Sb pollution in air. The sources analysis results based on Pb isotopes indicated that the proportion of Pb and Sb from coal-fired fly ash was the highest in winter (47.7%) and inclined to road dust in spring (34.5%), but it was mainly from traffic emissions in summer and autumn (34.2% and 32.8%). This study showed that Pb isotope tracing can be applied to predict the potential pollution sources, and it was also a feasible substitute for tracing Sb pollution in PM2.5.


Assuntos
Poluentes Atmosféricos , Material Particulado , Material Particulado/análise , Antimônio/análise , Cinza de Carvão/análise , Chumbo/análise , Monitoramento Ambiental/métodos , Poluentes Atmosféricos/análise , Poeira/análise , Estações do Ano , Isótopos/análise , Carvão Mineral/análise
19.
Artigo em Inglês | MEDLINE | ID: mdl-37015119

RESUMO

Under the situation of severe COVID-19 epidemic, lung ultrasound (LUS) has been proved to be an effective and convenient method to diagnose and evaluate the extent of respiratory disease. However, the traditional clinical ultrasound (US) scanning requires doctors not only to be in close contact with patients, but also to have rich experience. In order to alleviate the shortage of medical resources and reduce the work stress and risk of infection for doctors, we propose a visual perception and convolutional neural network(CNN) based robotic autonomous LUS scanning localization system to realize scanned target recognition, probe pose solution and movement, and the acquisition of US images. The LUS scanned targets are identified through the target segmentation and localization algorithm based on the improved CNN, which is using the depth camera to collect the image information; Furthermore, the method based on multi-scale compensation normal vector is used to solve the attitude of the probe; Finally, a position control strategy based on force feedback is designed to optimize the position and attitude of the probe, which can not only obtain high-quality US images but also ensure the safety of patients and the system. The results of human LUS scanning experiment verify the accuracy and feasibility of the system. The positioning accuracy of the scanned targets is 15.63±0.18 mm, and the distance accuracy and rotation angle accuracy of the probe position calculation are 6.38 ± 0.25 mm and 8.60 ± 2.29 degrees, respectively. More importantly, the obtained high-quality US images can clearly capture the main pathological features of the lung. The system is expected to be applied in clinical practice.

20.
Cell Rep ; 42(4): 112400, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37071536

RESUMO

Dysregulated amino acid increases the risk for heart failure (HF) via unclear mechanisms. Here, we find that increased plasma tyrosine and phenylalanine levels are associated with HF. Increasing tyrosine or phenylalanine by high-tyrosine or high-phenylalanine chow feeding exacerbates HF phenotypes in transverse aortic constriction and isoproterenol infusion mice models. Knocking down phenylalanine dehydrogenase abolishes the effect of phenylalanine, indicating that phenylalanine functions by converting to tyrosine. Mechanistically, tyrosyl-tRNA synthetase (YARS) binds to ataxia telangiectasia and Rad3-related gene (ATR), catalyzes lysine tyrosylation (K-Tyr) of ATR, and activates the DNA damage response (DDR) in the nucleus. Increased tyrosine inhibits the nuclear localization of YARS, inhibits the ATR-mediated DDR, accumulates DNA damage, and elevates cardiomyocyte apoptosis. Enhancing ATR K-Tyr by overexpressing YARS, restricting tyrosine, or supplementing tyrosinol, a structural analog of tyrosine, promotes YARS nuclear localization and alleviates HF in mice. Our findings implicate facilitating YARS nuclear translocation as a potential preventive and/or interfering measure against HF.

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