[Clinical characteristics and prognosis of childhood acute lymphoblastic leukemia with CD123 expression]. / CD123è¡¨è¾¾çš„å„¿ç«¥æ€¥æ€§æ·‹å·´ç»†èƒžç™½è¡€ç— çš„ä¸´åºŠç‰¹å¾åŠé¢„åŽåˆ†æž.

OBJECTIVES: To investigate the expression of CD123 in children with acute lymphoblastic leukemia (ALL) and its effect on the clinical characteristics and prognosis of children with B-lineage acute lymphoblastic leukemia (B-ALL). METHODS: A retrospective analysis was conducted on the clinical data of 251 children with ALL who were admitted to the Department of Hematology and Oncology, Children's Hospital of Kunming Medical University, from December 2019 to June 2022. According to the expression of CD123 at initial diagnosis, the children were divided into CD123+ group and CD123- group, and the two groups were compared in terms of clinical characteristics and treatment outcome. The factors influencing the prognosis were analyzed. RESULTS: Among the 251 children with ALL, there were 146 children (58.2%) in the CD123+ group. The B-ALL group had a significantly higher positive expression rate of CD123 than the acute T lymphocyte leukemia group (P<0.05). Compared with the CD123- group, the CD123+ group had significantly lower peripheral blood leukocyte count and percentage of juvenile cells and a significantly higher proportion of children with high hyperdiploid karyotype or an age of 1-10 years, with a relatively low proportion of children with E2A-PBX1 fusion gene (P<0.05). The multivariate Cox proportional-hazards regression model analysis showed that compared with the >10 years group, the 1-10 years group had a significantly higher overall survival rate (P<0.05), and compared with the high risk group, the moderate risk group had a significantly higher event-free survival rate in children with B-ALL (P<0.05). CONCLUSIONS: CD123 is widely expressed in children with B-ALL, and positive expression of CD123 might be an indicator for good prognosis in children with B-ALL, which is of great significance for evaluating the efficacy of remission induction therapy and survival prognosis of children with B-ALL.

Methods for multiancestry genome-wide association study meta-analysis.

Genome-wide association studies (GWAS) have significantly enhanced our understanding of the genetic basis of complex diseases. Despite the technological advancements, gaps in our understanding remain, partly due to small effect sizes and inadequate coverage of genetic variation. Multiancestry GWAS meta-analysis (MAGMA) addresses these challenges by integrating genetic data from diverse populations, thereby increasing power to detect loci and improving fine-mapping resolution to identify causal variants across different ancestry groups. This review provides an overview of the protocols, statistical methods, and software of MAGMA, as well as highlighting some challenges associated with this approach.

Microfluidic fabrication of monodisperse microcapsules with gas cores.

A facile strategy for efficient and continuous fabrication of monodisperse gas-core microcapsules with controllable sizes and excellent ultrasound-induced burst performances is developed based on droplet microfluidics and interfacial polymerization. Monodisperse gas-in-oil-in-water (G/O/W) double emulsion droplets with a gas core and monomer-contained oil layer are fabricated in the upstream of a microfluidic device as templates, and then water-soluble monomers are added into the aqueous continuous phase in the downstream to initiate rapid interfacial polymerization at the O/W interfaces to prepare monodisperse gas-in-oil-in-solid (G/O/S) microcapsules with gas cores. The sizes of both microbubbles and G/O/W droplet templates can be precisely controlled by adjusting the gas supply pressure and the fluid flow rates. Due to the very thin shells of G/O/S microcapsules fabricated via interfacial polymerization, the sizes of the resultant G/O/S microcapsules are almost the same as those of the G/O/W droplet templates, and the microcapsules exhibit excellent deformable properties and ultrasound-induced burst performances. The proposed strategy provides a facile and efficient route for controllably and continuously fabricating monodisperse microcapsules with gas cores, which are highly desired for biomedical applications.

A proteomics study of rheumatoid arthritis patients on etanercept identifies putative biomarkers associated with clinical outcome measures.

OBJECTIVES: Biologic DMARDs (bDMARDs) are widely used in patients with RA, but response to bDMARDs is heterogeneous. The objective of this work was to identify pretreatment proteomic biomarkers associated with RA clinical outcome measures in patients starting bDMARDs. METHODS: Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used to generate spectral maps of sera from patients with RA before and after 3 months of treatment with the bDMARD etanercept. Protein levels were regressed against RA clinical outcome measures, i.e. 28-joint DAS (DAS28) and its subcomponents and DAS28 <2.6 (i.e. remission). The proteins with the strongest evidence for association were analysed in an independent, replication dataset. Finally, subnetwork analysis was carried out using the Disease Module Detection algorithm and biological plausibility of identified proteins was assessed by enrichment analysis. RESULTS: A total of 180 patients with RA were included in the discovery dataset and 58 in the validation dataset from a UK-based prospective multicentre study. Ten individual proteins were found to be significantly associated with RA clinical outcome measures. The association of T-complex protein 1 subunit η with DAS28 remission was replicated in an independent cohort. Subnetwork analysis of the 10 proteins from the regression analysis identified the ontological theme, with the strongest associations being with acute phase and acute inflammatory responses. CONCLUSION: This longitudinal study of 180 patients with RA commencing etanercept has identified several putative protein biomarkers of treatment response to this drug, one of which was replicated in an independent cohort.

Ferroelectricity of ice nanotube forests grown in three-dimensional graphene: the electric field effect.

Generating diverse ferroelectric ice nanotubes (NTs) efficiently has always been challenging, but matters in nanomaterial synthesis and processing technology. In the present work, we propose a method of growing ice NT forests in a single cooling process. A three-dimensional (3D) graphene structure was selected to behave as a representative container in which a batch of (5, 0) ice NTs was formed simultaneously under the cooling process from molecular dynamics simulation. Other similar 3D graphene structures but with different hole configurations, like uniform triangle or both triangle and pentagon, were also tested, revealing that ice NTs with different tube indices, i.e. both (3, 0) and (5, 0), could also be formed at the same time. Intriguingly, the orientations of the dipole moments of the water molecules of an ice NT formed were independent of each other, making the net ferroelectricity of the whole system weakened or even cancelled. An electric field could help change the orientation of the water molecules of the already obtained ice NTs and even twist the tube to be a spiral (5, 1) one if it was applied during the cooling process, such that the net ferroelectricity was greatly improved. The underlying physical mechanism of all phase transition phenomena, including the improvement of the ferroelectricity under an electric field, were explored in depth from the phase transition curves and structural point of view. The obtained results are of significant application value for improving the preparation efficiency of nano-ferroelectric materials, which are prosperous in nano-devices.

Optimizing the Structure and Electrochemical Properties of Benzoquinone-Embedded COF via Heat Treatment for a High-Energy Organic Cathode.

A benzoquinone-embedded aza-fused covalent organic framework (BQ COF) with the maximum loading of redox-active units per molecule was employed as a cathode for lithium-ion batteries (LIBs) to achieve high energy and power densities. The synthesis was optimized to obtain high crystallinity and improved electrochemical performance. Synthesis at moderate temperature followed by a solid-state reaction was found to be particularly useful for achieving good crystallinity and the activation of the COF. When used as a cathode for LIBs, very high discharge capacities of 513, 365, and 234 mAh g-1 were obtained at 0.1C, 1C, and 10C, respectively, showing a remarkable rate performance. More than 70% of the initial capacity was retained after 1000 cycles when the cathode was investigated for cyclic performance at 2.5C. We demonstrated that a straightforward heat treatment led to enhanced crystallinity, an optimized structure, and favorable morphology, resulting in enhanced electrode kinetics and an improved overall electrochemical behavior. A comparative study was conducted involving an aza-fused COF lacking carbonyl groups (TAB COF) and a small molecule containing phenazine and carbonyl (3BQ), providing useful insights into new material design. A full cell was assembled with graphite as the anode to assess the commercial feasibility of BQ COF, and a discharge capacity of 240 mAh g-1 was obtained at 0.5C. Furthermore, a pouch-type cell with a high discharge capacity and an excellent rate performance was assembled, demonstrating the practical applicability of our designed cathode. Considering the entire mass of the working electrode, a specific energy density of 492 Wh kg-1 and a power density of 492 W kg-1 were achieved at the high current density of 1C, which are comparable to those of commercially available cathodes. These results highlight the promise of organic electrode materials for next-generation lithium-ion batteries. Furthermore, this study provides a systematic approach for simultaneously designing organic materials with high power and energy densities.

Fluorinated Artificial Solid-Electrolyte-Interphase Layer for Long-Life Sodium Metal Batteries.

Sodium metal batteries have garnered significant attention due to their high theoretical specific capacity, cost effectiveness, and abundant availability. However, the propensity for dendritic sodium formation, stemming from the highly reactive nature of the sodium metal surface, poses safety concerns, and the uncontrollable formation of the solid-electrolyte interphase (SEI) leads to large cell impedance and battery failures. In this study, we present a novel approach where we have successfully developed a stable fluorinated artificial SEI layer on the sodium metal surface by employing various weight percentages of tin fluoride in a dimethyl carbonate solution, utilizing a convenient, cost-effective, and single-step method. The resulting fluoride-rich protective layer effectively stabilized the Na metal surfaces and significantly enhanced cycling stability. The engineered artificial SEI layer demonstrated an enhanced lifetime of Na metal symmetric cells of over 3.5 times, over 700 h at the current density of 0.25 mA/cm2, in cycling performance compared to the untreated sodium, which is attributed to the suppression of dendrite formation and the reduction of undesired SEI formation during high-current cycling.

The hamburger-shape photocatalyst: thioxanthone-based chiral [2.2]paracyclophane for enantioselective visible-light photocatalysis of 3-methylquinoxalin-2(1H)-one and styrenes.

A new thioxanthone-based photocatalyst with a [2.2]paracyclophane skeleton and planar chirality has been developed. The catalyst has been successfully applied in the visible light-mediated enantioselective aza Paternò-Büchi reactions of quinoxalinone and styrenes to produce azetidines. The structures of the catalyst derivatives were unequivocally determined by their single crystal X-ray crystallography analysis.

Using Polygenic Risk Scores to Aid Diagnosis of Patients With Early Inflammatory Arthritis: Results From the Norfolk Arthritis Register.

OBJECTIVE: There is growing evidence that genetic data are of benefit in the rheumatology outpatient setting by aiding early diagnosis. A genetic probability tool (G-PROB) has been developed to aid diagnosis has not yet been tested in a real-world setting. Our aim was to assess whether G-PROB could aid diagnosis in the rheumatology outpatient setting using data from the Norfolk Arthritis Register (NOAR), a prospective observational cohort of patients presenting with early inflammatory arthritis. METHODS: Genotypes and clinician diagnoses were obtained from patients from NOAR. Six G-probabilities (0%-100%) were created for each patient based on known disease-associated odds ratios of published genetic risk variants, each corresponding to one disease of rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, spondyloarthropathy, gout, or "other diseases." Performance of the G-probabilities compared with clinician diagnosis was assessed. RESULTS: We tested G-PROB on 1,047 patients. Calibration of G-probabilities with clinician diagnosis was high, with regression coefficients of 1.047, where 1.00 is ideal. G-probabilities discriminated clinician diagnosis with pooled areas under the curve (95% confidence interval) of 0.85 (0.84-0.86). G-probabilities <5% corresponded to a negative predictive value of 96.0%, for which it was possible to suggest >2 unlikely diseases for 94% of patients and >3 for 53.7% of patients. G-probabilities >50% corresponded to a positive predictive value of 70.4%. In 55.7% of patients, the disease with the highest G-probability corresponded to clinician diagnosis. CONCLUSION: G-PROB converts complex genetic information into meaningful and interpretable conditional probabilities, which may be especially helpful at eliminating unlikely diagnoses in the rheumatology outpatient setting.

[Three surgical strategies for the treatment of intercourse-related hematuria in males: A summary of clinical experience].

OBJECTIVE: To summarize the clinical experience in the treatment of sexual intercourse-related hematuria in males using biopsy forceps, electrocoagulation and holmium laser cauterization. METHODS: From July 2018 to April 2022, we treated 11 male patients with intercourse-related hematuria using biopsy forceps, electrocoagulation and holmium laser cauterization. The patients ranged in age from 29 to 47 years, with clinical manifestations of gross hematuria, blood dripping from the urethral orifice or blood clots in the urine after sexual intercourse or erection, 3 with hemospermia, but none with pain. All the patients received urological imaging examination to exclude lesions in the upper urinary tract and bladder preoperatively. During the operation, varicose vessels were found around the posterior urethral verumontanum under the cystourethroscope in all the cases, 5 with active bleeding in the posterior varicose vessel. The 3 cases with hemospermia first underwent trans-prostatic utricle seminal vesiculoscopy. According to the range and number of varicose vessels, 5 of the patients were treated by electrocoagulation with the resectoscope, 2 by holmium laser cauterization and the other 4 with biopsy forceps to destroy the vascular tissue. After the operation, urinary catheters were retained for 3－7 days, abstinence lasted 30 days, and the patients were followed up for 6 months. RESULTS: The operations were successfully completed in all the cases, 10 with good prognosis and none with recurrence. Occasional postoperative hematuria and blood clots in the urine were observed in 1 of the patients treated by electrocoagulation under the resectoscope, with dysuria at 3 months after operation, who underwent repeated electrocoagulation and experienced no more recurrence thereafter. Different degrees of postoperative urethral irritation and gross hematuria were found in all the cases, which spontaneously disappeared within 1－4 weeks, with no such complications as ED, ejaculation pain, ejaculation difficulty and ejaculation weakness. CONCLUSION: In the absence of other genitourinary diseases, painless hematuria, blood clots in the urine or even dysuria in males after sexual intercourse can be considered as the results of possible varicose veins around the posterior urethral verumontanum, which can be treated satisfactorily by destroying the vascular tissue with biopsy forceps, electrocoagulation with the resectoscope or holmium laser cauterization according to the location, number and degree of varicose veins.

Production of high-energy 6-Ah-level Li | |LiNi0.83Co0.11Mn0.06O2 multi-layer pouch cells via negative electrode protective layer coating strategy.

Stable lithium metal negative electrodes are desirable to produce high-energy batteries. However, when practical testing conditions are applied, lithium metal is unstable during battery cycling. Here, we propose poly(2-hydroxyethyl acrylate-co-sodium benzenesulfonate) (PHS) as negative electrode protective layer. The PHS contains soft poly (2-hydroxyethyl acrylate) and poly(sodium p-styrene sulfonate), which improve electrode flexibility, connection with the Cu current collector and transport of Li ions. Transmission electron cryomicroscopy measurements reveal that PHS induces the formation of a solid electrolyte interphase with a fluorinated rigid and crystalline internal structure. Furthermore, theoretical calculations suggest that the -SO3- group of poly(sodium p-styrene sulfonate) promotes Li-ion motion towards interchain migration through cation-dipole interaction, thus, enabling uniform Li-ion diffusion. Electrochemical measurements of Li | |PHS-coated-Cu coin cells demonstrate an average Coulombic efficiency of 99.46% at 1 mA/cm2, 6 mAh/cm2 and 25 °C. Moreover, when the PHS-coated Li metal negative electrode is paired with a high-areal-capacity LiNi0.83Co0.11Mn0.06O2-based positive electrode in multi-layer pouch cell configuration, the battery delivers an initial capacity of 6.86 Ah (corresponding to a specific energy of 489.7 Wh/kg) and, a 91.1% discharge capacity retention after 150 cycles at 2.5 mA/cm2, 25 °C and 172 kPa.

Microfluidic Controllable Preparation of Iodine-131-Labeled Microspheres for Radioembolization Therapy of Liver Tumors.

Transcatheter arterial radioembolization (TARE) is of great significance for the treatment of advanced hepatocellular carcinoma (HCC). However, the existing radioembolic microspheres still have problems such as non-degradability, non-uniform size, and inability to directly monitor in vivo, which hinders the development of TARE. In this paper, a novel radioembolic agent, 131 I-labeled methacrylated gelatin microspheres (131 I-GMs), is prepared for the treatment of HCC. Water-in-oil (W/O) emulsion templates are prepared by a simple one-step microfluidic method to obtain methacrylated gelatin microspheres (GMs) after UV irradiation. A series of GMs with uniform and controllable size is obtained by adjusting the flow rate of each fluid. Both air-dried and freeze-dried GMs can quickly restore their original shape and size, and still have good monodispersity, elasticity, and biocompatibility. The radiolabeling experiments show that 131 I can efficiently bind to GMs by chloramine-T method, and the obtained 131 I-GMs have good radioactive stability in vitro. The results of in vivo TARE treatment in rats show that 131 I-GMs can be well retained in the hepatic artery and have a good inhibitory effect on the progression of liver cancer, showing the potential for the treatment of HCC.

Respiratory eukaryotic virome expansion and bacteriophage deficiency characterize childhood asthma.

Asthma development and exacerbation is linked to respiratory virus infections. There is limited information regarding the presence of viruses during non-exacerbation/infection periods. We investigated the nasopharyngeal/nasal virome during a period of asymptomatic state, in a subset of 21 healthy and 35 asthmatic preschool children from the Predicta cohort. Using metagenomics, we described the virome ecology and the cross-species interactions within the microbiome. The virome was dominated by eukaryotic viruses, while prokaryotic viruses (bacteriophages) were independently observed with low abundance. Rhinovirus B species consistently dominated the virome in asthma. Anelloviridae were the most abundant and rich family in both health and asthma. However, their richness and alpha diversity were increased in asthma, along with the co-occurrence of different Anellovirus genera. Bacteriophages were richer and more diverse in healthy individuals. Unsupervised clustering identified three virome profiles that were correlated to asthma severity and control and were independent of treatment, suggesting a link between the respiratory virome and asthma. Finally, we observed different cross-species ecological associations in the healthy versus the asthmatic virus-bacterial interactome, and an expanded interactome of eukaryotic viruses in asthma. Upper respiratory virome "dysbiosis" appears to be a novel feature of pre-school asthma during asymptomatic/non-infectious states and merits further investigation.

Surfactant Additives Containing Hydrophobic Fluorocarbon Chains and Hydrophilic Sulfonate Anion for Highly Reversible Zn Anode.

Aqueous zinc-ion batteries (AZIBs) show enormous potential as a large-scale energy storage technique. However, the growth of Zn dendrites and serious side reactions occurring at the Zn anode hinder the practical application of AZIBs. For the first time, we reported a fluorine-containing surfactant, i.e., potassium perfluoro-1-butanesulfonate (PPFBS), as an additive to the 2 M ZnSO4 electrolyte. Benefitting from its hydrophilic sulfonate anion and hydrophobic long fluorocarbon chain, PPFBS can promote the uniform distribution of Zn2+ flux at the anode/electrolyte interface, allowing the Zn/Zn cell to cycle for 2200 h. Furthermore, PPFBS could inhibit side reactions due to the existence of the perfluorobutyl sulfonate (C4F9SO3-) adsorption layer and the presence of C4F9SO3- in the solvation structure of Zn2+. The former can reduce the amount of H2O molecules and SO42- in contact with the Zn anode and C4F9SO3- entering the Zn2+-solvation structure by replacing SO42-. The Zn/Cu cell exhibits a superior average CE of 99.47% over 500 cycles. When coupled with the V2O5 cathode, the full cell shows impressive cycle stability. This work provides a simple, effective, and economical solution to the common issues of the Zn anode.

Optimization of 5'UTR to evade SARS-CoV-2 Nonstructural protein 1-directed inhibition of protein synthesis in cells.

Maximizing the expression level of therapeutic proteins in cells is the general goal for DNA/mRNA therapies. It is particularly challenging to achieve efficient protein expression in the cellular contexts with inhibited translation machineries, such as in the presence of cellular Nonstructural protein 1 (Nsp1) of coronaviruses (CoVs) that has been reported to inhibit overall protein synthesis of host genes and exogenously delivered mRNAs/DNAs. In this study, we thoroughly examined the sequence and structure contexts of viral and non-viral 5'UTRs that determine the protein expression levels of exogenously delivered DNAs and mRNAs in cells expressing SARS-CoV-2 Nsp1. It was found that high 5'-proximal A/U content promotes an escape from Nsp1-directed inhibition of protein synthesis and results in selective protein expression. Furthermore, 5'-proximal Cs were found to significantly enhance the protein expression in an Nsp1-dependent manner, while Gs located at a specific window close to the 5'-end counteract such enhancement. The distinct protein expression levels resulted from different 5'UTRs were found correlated to Nsp1-induced mRNA degradations. These findings ultimately enabled rational designs for optimized 5'UTRs that lead to strong expression of exogenous proteins regardless of the translationally repressive Nsp1. On the other hand, we have also identified several 5'-proximal sequences derived from host genes that are capable of mediating the escapes. These results provided novel perspectives to the optimizations of 5'UTRs for DNA/mRNA therapies and/or vaccinations, as well as shedding light on the potential host escapees from Nsp1-directed translational shutoffs. KEY POINTS: • The 5'-proximal SL1 and 5a/b derived from SARS-CoV-2 genomic RNA promote exogenous protein synthesis in cells expressing Nsp1 comparing with non-specific 5'UTRs. • Specific 5'-proximal sequence contexts are the key determinants of the escapes from Nsp1-directed translational repression and thereby enhance protein expressions. • Systematic mutagenesis identified optimized 5'UTRs that strongly enhance protein expression and promote resistance to Nsp1-induced translational repression and RNA degradation.

Gancao Nourishing-Yin decoction combined with methotrexate in treatment of aging CIA mice: a study based on DIA proteomic analysis.

BACKGROUND: Elderly rheumatoid arthritis (ERA) population faces multiple treatment dilemma. Here we aim to investigate if Gancao Nourishing-Yin decoction (GCNY) added to methotrexate (MTX) exhibit better effects in an ERA mice model. METHODS: ERA mice model was established by adding D-galactose (Dgal) to collagen-induced arthritis (CIA) mice. The model was then assigned into control group (CIA + Dgal), MTX treatment group (MTX), GCNY treatment group (GCNY), and integrative treatment group (MTX + GCNY). Pathological scoring was performed to evaluate the severity between the groups. Proteomic analysis was applied to investigate the secretory phenotype of the ERA mouse model and the underlying mechanism of GCNY, MTX and their combination. Representative cytokines related to proteomic results were further validated by ELISAs. RESULTS: CIA + Dgal mice showed more aggressive joints damage than the CIA mice. Besides changes in the inflammatory pathway such as Pi3k-Akt signaling pathway in both model, differential expressed proteins (DEPs) indicated metabolism-related pathways were more obvious in CIA + Dgal mice. Low-dose MTX failed to show pathological improvement in CIA + Dgal mice, while GCNY improved joints damage significantly. Besides down-regulated inflammation-related targets, GCNY-regulated DEPs (such as Apoc1 ~ 3, Grk2 and Creb3l3) were broadly enriched in metabolism-related pathways. MTX + GCNY showed the best therapeutic effect, and the DEPs enriched in a variety of inflammatory,metabolism and osteoclast differentiation signaling pathway. Notably, MTX + GCNY treatment up-regulated Dhfr, Cbr1, Shmt1 involved in folic acid biosynthesis and anti-folate resistance pathways indicated a coincidence synergic action. ELISAs confirmed CPR and Akt that elevated in CIA + Dgal mice were significantly ameliorated by treatments, and adding on GCNY elevated folic acid levels and its regulator Dhfr. CONCLUSION: Aging aggravated joints damage in CIA, which probably due to metabolic changes rather than more severe inflammation. GCNY showed significant effects in the ERA mice model especially when integrated with MTX to obtain a synergic action.

Cardiomyocyte-specific Peli1 contributes to the pressure overload-induced cardiac fibrosis through miR-494-3p-dependent exosomal communication.

Cardiac fibrosis is an essential pathological process in pressure overload (PO)-induced heart failure. Recently, myocyte-fibroblast communication is proven to be critical in heart failure, in which, pathological growth of cardiomyocytes (CMs) may promote fibrosis via miRNAs-containing exosomes (Exos). Peli1 regulates the activation of NF-κB and AP-1, which has been demonstrated to engage in miRNA transcription in cardiomyocytes. Therefore, we hypothesized that Peli1 in CMs regulates the activation of cardiac fibroblasts (CFs) through an exosomal miRNA-mediated paracrine mechanism, thereby promoting cardiac fibrosis. We found that CM-conditional deletion of Peli1 improved PO-induced cardiac fibrosis. Moreover, Exos from mechanical stretch (MS)-induced WT CMs (WT MS-Exos) promote activation of CFs, Peli1-/- MS-Exos reversed it. Furthermore, miRNA microarray and qPCR analysis showed that miR-494-3p was increased in WT MS-Exos while being down regulated in Peli1-/- MS-Exos. Mechanistically, Peli1 promoted miR-494-3p expression via NF-κB/AP-1 in CMs, and then miR-494-3p induced CFs activation by inhibiting PTEN and amplifying the phosphorylation of AKT, SMAD2/3, and ERK. Collectively, our study suggests that CMs Peli1 contributes to myocardial fibrosis via CMs-derived miR-494-3p-enriched exosomes under PO, and provides a potential exosomal miRNA-based therapy for cardiac fibrosis.