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1.
J Nanosci Nanotechnol ; 21(3): 1578-1589, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33404421

RESUMO

This work investigated the effect of hydroxyapatite (HA) nanorods on the strength development and hydration of cement. Undispersed HA nanorods (HA-UD) and dispersed HA nanorods (HA-DN) were prepared by atom-efficient neutralization. The strength of mortars modified by HA nanorods was tested, as well as their compatibility with supplementary cementitious material. The hydration of HA-modified cement pastes was characterized via in situ X-ray diffraction, isothermal calorimetry and scanning electron microscopy. As the results suggest, the undispersed HA-DN caused a considerable increase in superplasticizer demand to achieve the same level of flow. Both HA nanorods showed a significant accelerating effect on early hydration, with approximately 100% strength enhancement at 12 h at 2.0% dosage. The effect on early strength of the nanorods is retained in systems with up to 30% fly ash in the binder mass. According to the characterizations, the rate of the hydration reaction in the acceleration period was enhanced by HA nanorods, and C3S consumption was also increased. In all of the testing situations, HA-DN showed superior performance, likely due to improved spatial distribution of the hydroxyapatites. The results suggest that proper dispersion of the nanorods is necessary to optimize its performance.

3.
J Hazard Mater ; 403: 124075, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33265063

RESUMO

Low pH and high salinity characteristic of produced water (PW) posed a big challenge for the direct biological treatment. The immobilization of R. qingshengii strain FF, which degraded petroleum effectively under low pH, and application of immobilized R. qingshengii strain FF in treating mimic PW was studied in this work. The immobilization of R. qingshengii strain FF on the surface of polyethylene foam (PEF), one type of waste packaging materials, was optimized using the response surface methodology. Under optimum conditions, cell density of R. qingshengii strain FF immobilized on the surface of PEF reached 388 mg (cells)/g(PEF). In addition, a few factors, including hydraulic retention time (HRT), pH and salinity, were studied for treating mimic PW using immobilized R. qingshengii strain FF. The result of this study demonstrated that TPH degradation efficiency of PW by immobilized R. qingshengii strain FF reached above 90% when HRT was longer than 8 h. Weak acid and high salinity conditions only moderately decreased TPH. Asphalt, alkanes and aromatic hydrocarbon contained in petroleum can be degraded to some extent. These results indicated that immobilized R. qingshengii strain FF can be used as a highly efficient strain which could be used in biological treatment of real PW.

4.
New Phytol ; 229(1): 284-295, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32761622

RESUMO

Traits are critical in predicting decomposition that fuels carbon and nutrient cycling in ecosystems. However, our understanding of root trait-decomposition linkage, and especially its dependence on mycorrhizal type and environmental context, remains limited. We explored the control of morphological and chemical (carbon- and nutrient-related) traits over decomposition of absorptive roots in 30 tree species associated with either arbuscular mycorrhizal (AM) or ectomycorrhizal (ECM) fungi in temperate and subtropical forests in China. Carbon-related traits (acid-unhydrolysable residue (AUR) and cellulose concentrations) had predominant control of root decomposition in AM species while nutrient-related traits (magnesium concentration) predominately controlled that in ECM species. Thicker absorptive roots decomposed faster in AM species as a result of their lower AUR concentrations, but more slowly in ECM angiosperm species potentially as a result of their higher magnesium concentrations. Root decomposition was linked to root nutrient economy in both forests while root diameter-decomposition coordination emerged only in the subtropical forest where root diameter and decomposition presented similar cross-species variations. Our findings suggest that root trait-decomposition linkages differ strongly with mycorrhizal type and environment, and that root diameter can predict decomposition but in opposing directions and with contrasting mechanisms for AM and ECM species.

5.
Sensors (Basel) ; 21(1)2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33374742

RESUMO

Nanopores have a unique advantage for detecting biomolecules in a label-free fashion, such as DNA that can be synthesized into specific structures to perform computations. This method has been considered for the detection of diseased molecules. Here, we propose a novel marker molecule detection method based on DNA logic gate by deciphering a variable DNA tetrahedron structure using a nanopore. We designed two types of probes containing a tetrahedron and a single-strand DNA tail which paired with different parts of the target molecule. In the presence of the target, the two probes formed a double tetrahedron structure. As translocation of the single and the double tetrahedron structures under bias voltage produced different blockage signals, the events could be assigned into four different operations, i.e., (0, 0), (0, 1), (1, 0), (1, 1), according to the predefined structure by logic gate. The pattern signal produced by the AND operation is obviously different from the signal of the other three operations. This pattern recognition method has been differentiated from simple detection methods based on DNA self-assembly and nanopore technologies.

6.
Huan Jing Ke Xue ; 41(12): 5509-5517, 2020 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-33374067

RESUMO

There were significant differences in the working efficiency and mechanism of constructed wetlands between low temperature and suitable temperature conditions. This study designed a horizontal subsurface flow constructed wetland (HFCW) and a vertical subsurface flow constructed wetland (VFCW) to explore their performance differences in advanced treatment of sewage based on contaminant degradation analysis including the removal of organic matters, total nitrogen (TN), and total phosphorus (TP), as well as the analysis of microbial community structure. The results showed that when the COD concentration of influent was between 37.50 to 80.00 mg·L-1, the concentration of total nitrogen and total phosphorus were within the first level A criteria specified in the discharge standard of pollutants for municipal wastewater treatment plant at the continuous flow of 2 m3·d-1:①Both HFCW and VFCW showed stable degradation ability of organic matter in influent and good resistance to high organic load. ②Supplementation of the carbon source significantly improved the nitrogen removal efficiency of two subsurface flow constructed wetlands. HFCW achieved the average removal rate of TN at 76.01%, and the average removal rate of TN by VFCW reached 71.69% after the carbon addition. In contrast, dosage of an external carbon source showed limited effect on phosphorus removal. Furthermore, it worked more effectively for performance improvement of HFCW than that of VFCW. ③The analysis of microbial community structure in wetland substrate and plant rhizosphere samples revealed that Proteobacteria, Firmicutes, and Verrucomicrobia were the dominant phylum in two series of wetland samples. For the dominant microbiota at the genus level, there were more significant differences in microbial community structure in wetland substrate samples than that in plant rhizosphere samples. Hydrogenophaga, Erysipelothrix, and Devosia contributed the most to the differences between the microbial communities of HFCW and VFCW. Overall, the species diversity and abundance of microbial samples from VFCW was higher than those from HFCW.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33274797

RESUMO

Herein, we report an Ag 1 single-atom catalyst (Ag 1 /MnO 2 ), which was synthesized from thermal transformation of Ag nanoparticles (NPs) and surface reconstruction of MnO 2 . The evolution process of Ag NPs to single atoms is firstly revealed by various techniques including in-situ ETEM, in-situ XRD and DFT calculations. The temperature-induced surface reconstruction process from MnO 2 (211) to (310) lattice plane is critical to firmly confine the existed surface of Ag single-atom, i.e. the thermal treatment and surface reconstruction of MnO 2 is the driving force for the formation of single Ag atoms. The as-obtained Ag 1 /MnO 2 achieved 95.7% Faradic efficiency at -0.85 V vs. RHE, and coupled with long-term stability for electrochemical CO 2 reduction reaction (CO 2 RR). DFT calculations indicated single Ag sites possessed high electronic density close to Fermi Level and could act as the only active sites in CO 2 RR. As a result, the Ag 1 /MnO 2 catalyst shows remarkable performance for CO 2 RR, far surpassing the conventional Ag nanosized catalyst (Ag NP /MnO 2 ) and other reported Ag-based catalysts.

8.
Br J Clin Pharmacol ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33283892

RESUMO

BACKGROUND: Tigecycline has been widely used to treat hospital-acquired pneumonia off-label since it is considerably effective against a wide range of multidrug-resistant bacteria. However, no recommended dosage for this indication has been evaluated, resulting in possible inadequate treatment. AIMS: The aims of this study are to establish the population pharmacokinetics model of tigecycline in Chinese patients with hospital-acquired pneumonia, as well as to evaluate the exposure-response relationship for the treatment of hospital-acquired pneumonia with multidrug-resistant gram negative bacteria. METHODS: A population pharmacokinetic analysis of tigecycline was conducted on pooled data from 328 blood samples obtained from 89 patients with hospital-acquired pneumonia (HAP). Tigecycline plasma concentrations were measured by two-dimensional liquid chromatographic system and the data were analyzed using the Phoenix NLMETM software. Exposure-response analyses for efficacy were performed based on the data from 79 HAP patients with multidrug resistant gram-negative infections. Classification and regression tree and logistic regression analyses were employed to identify which pharmacokinetic-pharmacodynamic indices and magnitudes were the significant predictors of tigecycline efficacy. RESULTS: A two-compartment model with zero-order absorption adequately described the data. A larger body weight was associated with increased central volume of distribution and clearance (p<0.005), and the increased age, baseline creatinine concentration and aspertate aminotransferase were associated with decreased clearance (p<0.005). The AUC0-12h ×V/MIC ratio, APACHEII score and combined pseudomonas aeruginosa infection are the strong predictors for tigecycline clinical response. Classification and regression tree analyses indicated that the combinations of APACHEII score<24 and AUC0-12h ×V/MIC ratio≥100 was associated with clinical success. CONCLUSIONS: The proposed PPK model may serve as the basis for estimating tigecycline exposure for pharmacokinetic-pharmacodynamic analyses, and the pharmacokinetic-pharmacodynamic index and magnitude found in this study could be used for designing proper dosage regimens of tigecycline.

9.
Toxicol Sci ; 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33367866

RESUMO

Organophosphate esters (OPEs) are used widely as flame retardants and plasticizers but much remains unknown about their potential toxicity. Previously, we reported that four individual OPEs suppress endochondral ossification in murine limb bud cultures. However, real-life exposure is to complex OPE mixtures. In the present study, we tested the hypothesis that a Canadian household dust-based OPE mixture will affect endochondral ossification in gestation day 13 CD1 mouse embryo limb buds expressing fluorescent markers for the major cell populations involved in the process: COL2A1-ECFP (proliferative chondrocytes), COL10A1-mCherry (hypertrophic chondrocytes), and COL1A1-YFP (osteoblasts). Limbs were cultured for six days in the presence of vehicle or dilutions of the OPE mixture (1/1,000,000, 1/600,000, and 1/300,000). All three OPE mixture dilutions affected cartilage template development and the progression of endochondral ossification, as indicated by the fluorescent markers. The expression of Sox9, the master regulator of chondrogenesis, was unchanged, but the expression of Runx2 and Sp7, which drive chondrocyte hypertrophy and osteoblastogenesis, was dilution-dependently suppressed. RNA sequencing revealed that exposure to the 1/300,000 dilution of the OPE mixture for 24 h downregulated 153 transcripts and upregulated 48 others by at least 1.5-fold. Downregulated transcripts were enriched for those related to the immune system and bone formation. In contrast, upregulated transcripts were enriched for those with stress response functions known to be regulated by ATF4 activation. Thus, exposure to the mixture of OPEs commonly found in house dust may have adverse effects on bone formation.

10.
Molecules ; 25(24)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33371407

RESUMO

The identification of aroma composition and key odorants contributing to aroma characteristics of white tea is urgently needed, owing to white tea's charming flavors and significant health benefits. In this study, a total of 238 volatile components were identified in the three subtypes of white teas using headspace solid-phase microextraction (HS-SPME) combined with comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS). The multivariate statistical analysis demonstrated that the contents of 103 volatile compounds showed extremely significant differences, of which 44 compounds presented higher contents in Baihaoyinzhen and Baimudan, while the other 59 compounds exhibited higher contents in Shoumei. The sensory evaluation experiment carried out by gas chromatography-olfactometry/mass spectrometry (GC-O/MS) revealed 44 aroma-active compounds, of which 25 compounds were identified, including 9 alcohols, 6 aldehydes, 5 ketones, and 5 other compounds. These odorants mostly presented green, fresh, floral, fruity, or sweet odors. Multivariate analyses of chemical characterization and sensory evaluation results showed that high proportions of alcohols and aldehydes form the basis of green and fresh aroma characteristic of white teas, and phenylethyl alcohol, γ-Nonalactone, trans-ß-ionone, trans-linalool oxide (furanoid), α-ionone, and cis-3-hexenyl butyrate were considered as the key odorants accounting for the different aroma characteristics of the three subtypes of white tea. The results will contribute to in-depth understand chemical and sensory markers associated with different subtypes of white tea, and provide a solid foundation for tea aroma quality control and improvement.

11.
Food Sci Nutr ; 8(10): 5748-5762, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33133576

RESUMO

Squid products are becoming more and more popular with consumers because of their high yields and nutrition, including novel textures with desirable sensory properties. However, it has not been determined whether the cooking method has effects on the flavor of the squid. In this study, the aroma and volatile substances of squid samples from different cooking methods (boiled, steamed, sous vide) were determined and analyzed by headspace-gas chromatography-ion mobility spectrometry and differentiated by using, as well, an electronic nose and sensory evaluation. A total of 43 characteristic flavor compounds were identified. Based on the signal intensity of the identified violate compounds, we established a fingerprint of heat-treated squid from different cooking methods. Due to the long-term low-temperature heating conditions under vacuum, the flavor of sous vide squid is different from steamed and boiled squid, and it has unique special flavor compounds. Different cooking methods can affect the aroma of squid, providing support for the industrial production of squid.

12.
Front Oncol ; 10: 524712, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240803

RESUMO

Vascular-targeted PDT (vPDT) has produced promising results in the treatment of many cancers, including drug-resistant ones, but little is known about its efficacy in lymphoma. Unfortunately, the lack of a specific therapeutic target and a hypoxic microenvironment for lymphoma jeopardizes the efficacy of vPDT severely. In this study, we designed a lymphoma tissue factor-targeted "O2-evolving" strategy combining PDT with catalase and HMME-encapsulated, EGFP-EGF1-modified PEG-PLGA nanoparticles (CENPs) to boost PDT efficiency; this combination takes advantage of the low oxygen tension of lymphoma. In our results, CENPs accumulated effectively in the vascular lymphoma in vivo and in vitro, and this accumulation increased further with PDT treatment. Per positron emission tomography imaging, combining CENPs with PDT inhibited lymphoma glucose metabolism significantly. The expression of hypoxia-inducible factor (HIF)-1α in the entrapped catalase groups reduced markedly. These data show that the combined administration of PDT and CENPs can prompt tissue factor-cascade-targeted and self-supply of oxygen and that it has a good therapeutic effect on malignant lymphoma.

13.
EBioMedicine ; 62: 103126, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33232873

RESUMO

BACKGROUND: The high heterogeneity of acute myeloid leukaemia (AML) reflected in the patient- and disease-related factors accounts for the unsatisfactory prognosis despite the introduction of novel therapeutic approaches and drugs in recent years. METHODS: In the development set (n = 412), parameters including age, hematopoietic cell transplantation-comorbidity index, white blood cell count, hemoglobin, biallelic CEBPA mutations, DNMT3A mutations, FLT3-ITD/NPM1 status, and ELN cytogenetic risk status were identified as independent prognostic factors for overall survival (OS) in the multivariable Cox regression analysis. A nomogram combining these predictors for individual risk estimation was established thereby. FINDINGS: The prognostic model demonstrated promising performance in the development cohort. The calibration plot, C-index (0.74), along with the 1-, 2- and 3-year area under the receiver operating characteristic curve (AUC, 0.76, 0.79, and 0.74, respectively) in the validation set (n = 238) substantiated the robustness of the model. In addition to stratifying young (age ≤ 60 years) and elderly patients (age > 60 years) into three and two risk groups with significant distinct outcomes, the prognostic model succeeded in distinguishing eligible candidates for hematopoietic stem cell transplantation. INTERPRETATION: The prognostic model is capable of survival prediction, risk stratification and helping with therapeutic decision-making with the use of easily acquired variables in daily clinical routine. FUNDING: This work was supported in part by grants from the National Natural Science Foundation of China (81770141), the National Key R&D Program of China (2016YFE0202800), and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20161406).

14.
Sleep ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175978

RESUMO

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a frequent cause for consultation and a defining symptom of narcolepsy and idiopathic hypersomnia (IH). The associated mechanisms remain unclear. Lipocalin-type prostaglandin D synthase (LPGDS) is a plausible sleep-inducing candidate. This study is to compare cerebral spinal fluid (CSF) and serum LPGDS levels in patients group with hypersomnia of central origin, including those with narcolepsy type 1 (NT1) and type 2 (NT2) and IH, to those in healthy controls (Con). METHODS: Serum LPGDS, CSF LPGDS and CSF hypocretin-1(Hcrt-1) levels were measured by ELISA in 122 narcolepsy patients (106 NT1, and 16 NT2), 27 IH, and 51Con. RESULTS: LPGDS levels in CSF (p=0.02) and serum (p<0.001) were 22-25% lower in control subjects than in patients with EDS complaints, including NT1, NT2 and IH. In contrast to significant differences in CSF Hcrt-1 levels, CSF L-PGDS levels and serum L-PGDS were comparable among NT1, NT2 and IH (p>0.05), except for slightly lower serum LPGDS in IH than in NT1(p=0.01). Serum L-PGDS correlated modestly and negatively to sleep latency on MSLT(r=-0.227, p=0.007) in hypersomnia subjects. CONCLUSIONS: As a somnogen-producing enzyme, CSF/serum LPGDS may serve as a new biomarker for EDS of central origin and imply a common pathogenetic association, but would complement rather than replaces orexin markers.

15.
Nanoscale ; 12(44): 22366-22385, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33150899

RESUMO

Two-dimensional materials (2Dm) offer a unique insight into the world of quantum mechanics including van der Waals (vdWs) interactions, exciton dynamics and various other nanoscale phenomena. 2Dm are a growing family consisting of graphene, hexagonal-Boron Nitride (h-BN), transition metal dichalcogenides (TMDs), monochalcogenides (MNs), black phosphorus (BP), MXenes and 2D organic crystals such as small molecules (e.g., pentacene, C8 BTBT, perylene derivatives, etc.) and polymers (e.g., COF and MOF, etc.). They exhibit unique mechanical, electrical, optical and optoelectronic properties that are highly enhanced as the surface to volume ratio increases, resulting from the transition of bulk to the few- to mono- layer limit. Such unique attributes include the manifestation of highly tuneable bandgap semiconductors, reduced dielectric screening, highly enhanced many body interactions, the ability to withstand high strains, ferromagnetism, piezoelectric and flexoelectric effects. Using 2Dm for mechanical resonators has become a promising field in nanoelectromechanical systems (NEMS) for applications involving sensors and condensed matter physics investigations. 2Dm NEMS resonators react with their environment, exhibit highly nonlinear behaviour from tension induced stiffening effects and couple different physics domains. The small size and high stiffness of these devices possess the potential of highly enhanced force sensitivities for measuring a wide variety of un-investigated physical forces. This review highlights current research in 2Dm NEMS resonators from fundamental physics and an applications standpoint, as well as presenting future possibilities using these devices.

16.
Cell Metab ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33186557

RESUMO

Efficient delivery of specific cargos in vivo poses a major challenge to the secretory pathway, which shuttles products encoded by ∼30% of the genome. Newly synthesized protein and lipid cargos embark on the secretory pathway via COPII-coated vesicles, assembled by the GTPase SAR1 on the endoplasmic reticulum (ER), but how lipid-carrying lipoproteins are distinguished from the general protein cargos in the ER and selectively secreted has not been clear. Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. While both genes are implicated in lipid regulation in humans, hepatic inactivation of either mouse Sar1b or Surf4 selectively depletes plasma lipids to near-zero and protects the mice from atherosclerosis. These findings show that the pairing between SURF4 and SAR1B synergistically operates a specialized, dosage-sensitive transport program for circulating lipids, while further suggesting a potential translation to treat atherosclerosis and related cardio-metabolic diseases.

17.
Front Oncol ; 10: 1712, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014849

RESUMO

Background: The incidence of Waldenström macroglobulinemia (WM) has increased in certain groups over several decades in the United States. It is unclear whether the increasing incidence is associated with mortality trends. Methods: The incidence and incidence-based mortality (IBM) rates were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (1980-2016) with SEER*Stat software. The secular trends stratified by demographic characteristics were analyzed by joinpoint regression. Results: The incidence of WM showed an initial rapid increase from 1980 to 1993 {annual percentage change (APC), 14.1% [95% confidence interval (CI), 10 to 18.4%]}, whereas it began to stabilize from 1993 to 2016 [APC, 0.5% (95% CI, -0.3 to 1.3%)]. The WM IBM trend followed a similar pattern, with a decrease occurring around 1994. The trends in the incidence and mortality significantly differed according to geographic location, race, age, sex, primary site of involvement and subtype, which could help in further investigations into the specific etiology. Moreover, a dramatic increase in the 5-year survival rate from the 1980s to 2010s was observed (47.84 vs. 69.41%). Conclusions: Although both the incidence and IBM of WM continued to increase during the study period, a reduction in the rate of increase occurred around 1993. We believe that further advances in healthcare delivery and research can ensure a low mortality rate. Future studies can use the findings of this paper to monitor the results of WM therapy.

18.
Nat Commun ; 11(1): 5411, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33110070

RESUMO

The novel coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, where the initial wave of intense community transmissions was cut short by interventions. Using multiple data sources, here we estimate the disease burden and clinical severity by age of COVID-19 in Wuhan from December 1, 2019 to March 31, 2020. Our estimates account for the sensitivity of the laboratory assays, prospective community screenings, and healthcare seeking behaviors. Rates of symptomatic cases, medical consultations, hospitalizations and deaths were estimated at 796 (95% CI: 703-977), 489 (472-509), 370 (358-384), and 36.2 (35.0-37.3) per 100,000 persons, respectively. The COVID-19 outbreak in Wuhan had a higher burden than the 2009 influenza pandemic or seasonal influenza in terms of hospitalization and mortality rates, and clinical severity was similar to that of the 1918 influenza pandemic. Our comparison puts the COVID-19 pandemic into context and could be helpful to guide intervention strategies and preparedness for the potential resurgence of COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Fatores Etários , Betacoronavirus/isolamento & purificação , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Encaminhamento e Consulta/estatística & dados numéricos , Risco , Índice de Gravidade de Doença
20.
Nat Cell Biol ; 22(11): 1319-1331, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33020597

RESUMO

PIWI-interacting RNAs (piRNAs) are abundantly expressed during cardiac hypertrophy. However, their functions and molecular mechanisms remain unknown. Here, we identified a cardiac-hypertrophy-associated piRNA (CHAPIR) that promotes pathological hypertrophy and cardiac remodelling by targeting METTL3-mediated N6-methyladenosine (m6A) methylation of Parp10 mRNA transcripts. CHAPIR deletion markedly attenuates cardiac hypertrophy and restores heart function, while administration of a CHAPIR mimic enhances the pathological hypertrophic response in pressure-overloaded mice. Mechanistically, CHAPIR-PIWIL4 complexes directly interact with METTL3 and block the m6A methylation of Parp10 mRNA transcripts, which upregulates PARP10 expression. The CHAPIR-dependent increase in PARP10 promotes the mono-ADP-ribosylation of GSK3ß and inhibits its kinase activity, which results in the accumulation of nuclear NFATC4 and the progression of pathological hypertrophy. Hence, our findings reveal that a piRNA-mediated RNA epigenetic mechanism is involved in the regulation of cardiac hypertrophy and that the CHAPIR-METTL3-PARP10-NFATC4 signalling axis could be therapeutically targeted for treating pathological hypertrophy and maladaptive cardiac remodelling.

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