Inhibitory effects of glutathione peroxidase on microbial spoilage of crayfish (Procambarus clarkii) during refrigerated storage.

The variety of enzyme-based biological preservatives is limited. This study evaluated the effects of glutathione peroxidase (GSH-Px) on the quality of crayfish during refrigerated storage by measuring the pH, total volatile basic nitrogen, trimethylamine, and microbial contamination in crayfish muscle simulation system. The results revealed that 0.3% GSH-Px (CK3) not only suppressed the degradation of nitrogenous substances but also decreased the contamination levels of total viable, Enterobacteriaceae, and Pseudomonas counts (P < 0.05). Furthermore, the populations of Lactococcus, Aeromonas, and Massilia differed in the CK3 group compared to the other groups (P < 0.05) at the end of the storage (day 15). Moreover, the principal coordinate analysis showed that the colony composition of CK3 stored for 15 days was similar to that of the control group stored for 10 days. Therefore, GSH-Px exhibits antibacterial activity against Gram-negative bacteria and has good application potential in freshwater aquatic product preservation.

Intratracheally Administered Peptide-Modified Lipid Admixture Containing Fasudil and/or DETA NONOate Ameliorates Various Pathologies of Pulmonary Arterial Hypertension.

This study examined the therapeutic potential of a combination therapy using fasudil, a Rho-kinase inhibitor, and DETA NONOate (DN), a nitric oxide donor, delivered as a lipid admixture modified with a cyclic homing peptide known as CAR (CAR-lipid mixture) for the treatment of pulmonary arterial hypertension (PAH). CAR-lipid mixtures were initially prepared via a thin-film hydration method and then combined with fasudil, DN, or a mixture of both. The therapeutic efficacy of this drug-laden lipid mixture was evaluated in a Sugen/Hypoxia (Su/Hx) rat model of PAH by measuring RV systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), Fulton indices, and assessing right ventricular (RV) functions, as well as evaluating pulmonary vascular morphology. Rats that received no treatment exhibited increases in RVSP, mPAP, Fulton indices, and changes in RV functional parameters. However, the treatment with the CAR-lipid mixture containing either fasudil or DN or a combination of both led to a decline in mPAP, RVSP, and Fulton indices compared to saline-treated rats. Similarly, rats that received these treatments showed concurrent improvement in various echocardiographic parameters such as pulmonary acceleration time (PAT), tricuspid annular plane systolic excursion (TAPSE), and ventricular free wall thickness (RVFWT). A significant decrease in the wall thickness of pulmonary arteries larger than 100 µm was observed with the combination therapy. The findings reveal that fasudil, DN, and their combination in a CAR-modified lipid mixture improved pulmonary hemodynamics, RV functions, and pathological alterations in the pulmonary vasculature. This study underscores the potential of combination therapy and targeted drug delivery in PAH treatment, laying the groundwork for future investigations into the optimization of these treatments, their long-term safety and efficacy, and the underlying mechanism of action of the proposed therapy.

Estrogen prevents age-dependent beige adipogenesis failure through NAMPT-controlled ER stress pathway.

Thermogenic beige adipocytes are recognized as potential therapeutic targets for combating metabolic diseases. However, the metabolic advantages they offer are compromised with aging. Here, we show that treating mice with estrogen (E2), a hormone that decreases with age, to mice can counteract the aging- related decline in beige adipocyte formation when subjected to cold, while concurrently enhancing energy expenditure and improving glucose tolerance. Mechanistically, we find that nicotinamide phosphoribosyltranferase (NAMPT) plays a pivotal role in facilitating the formation of E2-induced beige adipocytes, which subsequently suppresses the onset of age-related ER stress. Furthermore, we found that targeting NAMPT signaling, either genetically or pharmacologically, can restore the formation of beige adipocytes by increasing the number of perivascular adipocyte progenitor cells. Conversely, the absence of NAMPT signaling prevents this process. In conclusion, our findings shed light on the mechanisms governing the age-dependent impairment of beige adipocyte formation and underscore the E2-NAMPT controlled ER stress as a key regulator of this process. Highlights: Estrogen restores beige adipocyte failure along with improved energy metabolism in old mice.Estrogen enhances the thermogenic gene program by mitigating age-induced ER stress.Estrogen enhances the beige adipogenesis derived from SMA+ APCs.Inhibiting the NAMPT signaling pathway abolishes estrogen-promoted beige adipogenesis.

Catheterization of Pulmonary and Carotid Arteries for Concurrent Measurement of Mean Pulmonary and Systemic Arterial Pressure in Rat Models of Pulmonary Arterial Hypertension.

Pulmonary hypertension (PH) is a group of pulmonary vascular disorders in which mean pulmonary arterial pressure (mPAP) becomes abnormally high because of various pathological conditions, including remodeling of the pulmonary arteries, lung and heart disorders, or congenital conditions. Various animal models, including mouse and rat models, have been used to recapitulate elevated mPAP observed in PH patients. However, the measurement and recording of mPAP and mean systemic arterial pressure (mSAP) in small animals require microsurgical procedures and a sophisticated data acquisition system. In this paper, we describe the surgical procedures for right heart catheterizations (RHC) to measure mPAP in rats. We also explain the catheterization of the carotid artery for simultaneous measurement of mPAP and mSAP using the PowerLab Data Acquisition system. We enumerate the surgical steps involved in exposing the jugular vein and the carotid artery for catheterizing these two blood vessels. We list the tools used for microsurgery in rats, describe the methods for preparing catheters, and illustrate the process for inserting the catheters in the pulmonary and carotid arteries. Finally, we delineate the steps involved in the calibration and setup of the PowerLab system for recording both mPAP and mSAP. This is the first protocol wherein we meticulously explain the surgical procedures for RHC in rats and the recording of mPAP and mSAP. We believe this protocol will be essential for PH research. Investigators with little training in animal handling can reproduce this microsurgical procedure for RHC in rats and measure mPAP and mSAP in rat models of PH. Further, this protocol is likely to help master RHC in rats that are performed for other conditions, such as heart failure, congenital heart disease, heart valve disorders, and heart transplantation.

Cryoprotective Effects of Carrageenan Oligosaccharides on Crayfish (Procambarus clarkii) during Superchilling.

Cryoprotectants are widely used to protect muscle tissue from ice crystal damage during the aquatic products freezing process, but traditional phosphate cryoprotectants may cause an imbalance in the calcium-to-phosphorus ratio for the human body. This study evaluated the effects of carrageenan oligosaccharides (CRGO) on quality deterioration and protein hydrolysis of crayfish (Procambarus clarkii) during superchilling. The physical-chemical analyses showed that CRGO treatments could significantly (p < 0.05) inhibit the increase of pH values, TVB-N, total viable counts, and thawing loss, and improve the water holding capacity and the proportion of immobilized water, which indicated that CRGO treatment effectively delayed the quality deterioration of crayfish. The myofibrillar protein structural results demonstrated that the increase of the disulfide bond, carbonyl content, S0-ANS, and the decrease of total sulfhydryl content were suppressed significantly (p < 0.05) in CRGO treatment groups. Furthermore, SDS-PAGE results showed that the band intensity of myosin heavy chain and actin in CRGO treatment groups were stronger than in the control. Overall, the application of CRGO to crayfish might maintain better quality and stable protein structure during the superchilling process, and CRGO has the potential to replace phosphate as a novel cryoprotectant for aquatic products.

Role of macrophages in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary vascular disease characterized by progressive pulmonary artery pressure elevation, increased pulmonary vascular resistance and ultimately right heart failure. Studies have demonstrated the involvement of multiple immune cells in the development of PAH in patients with PAH and in experimental PAH. Among them, macrophages, as the predominant inflammatory cells infiltrating around PAH lesions, play a crucial role in exacerbating pulmonary vascular remodeling in PAH. Macrophages are generally polarized into (classic) M1 and (alternative) M2 phenotypes, they accelerate the process of PAH by secreting various chemokines and growth factors (CX3CR1, PDGF). In this review we summarize the mechanisms of immune cell action in PAH, as well as the key factors that regulate the polarization of macrophages in different directions and their functional changes after polarization. We also summarize the effects of different microenvironments on macrophages in PAH. The insight into the interactions between macrophages and other cells, chemokines and growth factors may provide important clues for the development of new, safe and effective immune-targeted therapies for PAH.

A cell-penetrating PHLPP peptide improves cardiac arrest survival in murine and swine models.

Out-of-hospital cardiac arrest is a leading cause of death in the US, with a mortality rate over 90%. Preclinical studies demonstrate that cooling during cardiopulmonary resuscitation (CPR) is highly beneficial, but can be challenging to implement clinically. No medications exist for improving long-term cardiac arrest survival. We have developed a 20-amino acid peptide, TAT-PHLPP9c, that mimics cooling protection by enhancing AKT activation via PH domain leucine-rich repeat phosphatase 1 (PHLPP1) inhibition. Complementary studies were conducted in mouse and swine. C57BL/6 mice were randomized into blinded saline control and peptide-treatment groups. Following a 12-minute asystolic arrest, TAT-PHLPP9c was administered intravenously during CPR and significantly improved the return of spontaneous circulation, mean arterial blood pressure and cerebral blood flow, cardiac and neurological function, and survival (4 hour and 5 day). It inhibited PHLPP-NHERF1 binding, enhanced AKT but not PKC phosphorylation, decreased pyruvate dehydrogenase phosphorylation and sorbitol production, and increased ATP generation in heart and brain. TAT-PHLPP9c treatment also reduced plasma taurine and glutamate concentrations after resuscitation. The protective benefit of TAT-PHLPP9c was validated in a swine cardiac arrest model of ventricular fibrillation. In conclusion, TAT-PHLPP9c may improve neurologically intact cardiac arrest survival without the need for physical cooling.

Hypoxia-induced pulmonary hypertension upregulates eNOS and TGF-ß contributing to sex-linked differences in BMPR2 +/R899X mutant mice.

Dysfunctional bone morphogenetic protein receptor 2 (BMPR2) and endothelial nitric oxide synthase (eNOS) have been largely implicated in the pathogenesis of pulmonary arterial hypertension (PAH); a life-threatening cardiopulmonary disease. Although the incident of PAH is about three times higher in females, males with PAH usually have a worse prognosis, which seems to be dependent on estrogen-associated cardiac and vascular protection. Here, we evaluated whether hypoxia-induced pulmonary hypertension (PH) in humanized BMPR2+/R899X loss-of-function mutant mice contributes to sex-associated differences observed in PAH by altering eNOS expression and inducing expansion of hyperactivated TGF-ß-producing pulmonary myofibroblasts. To test this hypothesis, male and female wild-type (WT) and BMPR2+/R899X mutant mice were kept under hypoxic or normoxic conditions for 4 weeks, and then right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) were measured. Chronic hypoxia exposure elevated RVSP, inducing RVH in both groups, with a greater effect in BMPR2+/R899X female mice. Lung histology revealed no differences in vessel thickness/area between sexes, suggesting RVSP differences in this model are unlikely to be in response to sex-dependent vascular narrowing. On the other hand, hypoxia exposure increased vascular collagen deposition, the number of TGF-ß-associated α-SMA-positive microvessels, and eNOS expression, whereas it also reduced caveolin-1 expression in the lungs of BMPR2+/R899X females compared to males. Taken together, this brief report reveals elevated myofibroblast-derived TGF-ß and eNOS-derived oxidants contribute to pulmonary microvascular muscularization and sex-linked differences in incidence, severity, and outcome of PAH.

Epidemiology-based analysis of the risks and elimination strategies of the monkeypox outbreak in 2022.

Human monkeypox, caused by monkeypox virus, has spread unprecedentedly to more than 100 countries since May 2022. Here we summarized the epidemiology of monkeypox through a literature review and elucidated the risks and elimination strategies of this outbreak mainly based on the summarized epidemiology. We demonstrated that monkeypox virus became more contagious and less virulent in 2022, which could result from the fact that the virus entered a special transmission network favoring close contacts (i.e., sexual behaviors of men who have sex with men outside Africa) and the possibility that the virus accumulated a few adaptive mutations. We gave the reasons to investigate whether cattle, goats, sheep, and pigs are susceptible to monkeypox virus and whether infection with monkeypox virus could be latent in some primates. We listed six potential scenarios for the future of the outbreak (e.g., the outbreak could lead to endemicity outside Africa with increased transmissibility or virulence). We also listed multiple factors aiding or impeding the elimination of the outbreak. We showed that the control measures strengthened worldwide after the World Health Organization declared the outbreak a public health emergency of international concern (PHEIC) could eliminate the outbreak in 2022. We clarified eight strategies, i.e., publicity and education, case isolation, vaccine stockpiling, risk-based vaccination or ring vaccination, importation quarantine, international collaboration, and laboratory management, for the elimination of the outbreak.

Sphingosine Kinase 1 Deficiency in Smooth Muscle Cells Protects against Hypoxia-Mediated Pulmonary Hypertension via YAP1 Signaling.

Sphingosine kinase 1 (SPHK1) and the sphingosine-1-phosphate (S1P) signaling pathway have been shown to play a role in pulmonary arterial hypertension (PAH). S1P is an important stimulus for pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary vascular remodeling. We aimed to examine the specific roles of SPHK1 in PASMCs during pulmonary hypertension (PH) progression. We generated smooth muscle cell-specific, Sphk1-deficient (Sphk1f/f TaglnCre+) mice and isolated Sphk1-deficient PASMCs from SPHK1 knockout mice. We demonstrated that Sphk1f/f TaglnCre+ mice are protected from hypoxia or hypoxia/Sugen-mediated PH, and pulmonary vascular remodeling and that Sphk1-deficient PASMCs are less proliferative compared with ones isolated from wild-type (WT) siblings. S1P or hypoxia activated yes-associated protein 1 (YAP1) signaling by enhancing its translocation to the nucleus, which was dependent on SPHK1 enzymatic activity. Further, verteporfin, a pharmacologic YAP1 inhibitor, attenuated the S1P-mediated proliferation of hPASMCs, hypoxia-mediated PH, and pulmonary vascular remodeling in mice and hypoxia/Sugen-mediated severe PH in rats. Smooth muscle cell-specific SPHK1 plays an essential role in PH via YAP1 signaling, and YAP1 inhibition may have therapeutic potential in treating PH.

Convolutional neural network-based portable computer vision system for freshness assessment of crayfish (Prokaryophyllus clarkii).

Developing novel techniques for freshness assessment are of the utmost importance in yield and trade of aquatic products. The crayfish (Prokaryophyllus clarkii) is one of the most popular freshwater products in China, and its food safety should be a serious concern. In this study, a convolutional neural network (CNN)-based portable computer vision system for freshness assessment of crayfish method was proposed. A portable microscope was utilized to collect the microscopic images of crayfish with different freshness levels. The convolutional neural network was constructed and then optimized to extract features from the microscopic images. For the pictures from the portable microscope, the prediction accuracies of freshness could be 86.5% and 83.3% when the optimized networks were applied. The results indicate that the convolutional neural network-based portable computer vision system may provide an alternative way for the freshness assessment in the crayfish industrial chain. PRACTICAL APPLICATION: Portable computer vision system was constructed by a portable microscope connected to a mobile phone. The freshness of crayfish could be rapidly assessed by analyzing the pictures of crayfish using the system. The convolutional neural network-based portable computer vision system may provide an alternative way for the freshness assessment in the crayfish industrial chain.

Oil Penetration of Batter-Breaded Fish Nuggets during Deep-Fat Frying: Effect of Frying Oils.

Four frying oils (rapeseed, soybean, rice bran, and palm oils) were employed either as received (fresh) or after preheating at 180 °C for 10 h, and measured for their fatty acid composition, viscosity, and dielectric constant. Batter-breaded fish nuggets (BBFNs) were fried at 180 °C (60 s), and the effect of the oils' quality on the oil penetration of fried BBFNs were investigated via the analysis of the absorption and the distribution of fat. Preheating increased the viscosity and dielectric constant of the oils. The total fat content using fresh oils was the greatest for palm oil (14.2%), followed by rice bran oil (12.2%), rapeseed oil (12.1%), and soybean oil (11.3%), a trend that was nearly consistent with the penetrated surface oil, except that the penetrated oil for soybean oil (6.8%) was higher than rapeseed oil (6.3%). The BBFNs which were fried using fresh oils possessed a more compact crust and smaller pores for the core and underwent a lower oil penetration compared to the preheated oils. The results suggested that the oils' quality significantly affected the oil penetration of fried BBFNs.

MicroRNA-212-5p, an anti-proliferative miRNA, attenuates hypoxia and sugen/hypoxia-induced pulmonary hypertension in rodents.

MicroRNAs (miRNA, miR-) play important roles in disease development. In this study, we identified an anti-proliferative miRNA, miR-212-5p, that is induced in pulmonary artery smooth muscle cells (PASMCs) and lungs of pulmonary hypertension (PH) patients and rodents with experimental PH. We found that smooth muscle cell (SMC)-specific knockout of miR-212-5p exacerbated hypoxia-induced pulmonary vascular remodeling and PH in mice, suggesting that miR-212-5p may be upregulated in PASMCs to act as an endogenous inhibitor of PH, possibly by suppressing PASMC proliferation. Extracellular vesicles (EVs) have been shown recently to be promising drug delivery tools for disease treatment. We generated endothelium-derived EVs with an enriched miR-212-5p load, 212-eEVs, and found that they significantly attenuated hypoxia-induced PH in mice and Sugen/hypoxia-induced severe PH in rats, providing proof of concept that engineered endothelium-derived EVs can be used to deliver miRNA into lungs for treatment of severe PH.

Extraction methods, physiological activities and high value applications of tea residue and its active components: a review.

Tea is a traditional plant beverage originating from China as one of the most popular beverages worldwide, which has been an important companion in modern society. Nevertheless, as the waste after tea processing, tea residues from agriculture, industry and kitchen waste are discarded in large quantities, resulting in waste of resources and environmental pollution. In recent years, the comprehensive utilization of tea residue resources has attracted people's attention. The bioactive components remaining in tea residues demonstrate a variety of health benefits and can be recycled using advanced extraction processes. Furthermore, researchers have been devoted to converting tea residues into derivatives such as biosorbents, agricultural compost, and animal feeds through thermochemical techniques and biotechnology. This review summarized the chemical composition and physiological activities of bioactive components from tea residue. The extraction methods of bioactive components in tea residue were elucidated and the main high-value applications of tea residues were proposed. On this basis, the utilization of tea residues can be developed from a single way to a multi-channel or cascade way to improve its economic efficiency. Novel applications of tea residues in different fields, including food development, environmental remediation, energy production and composite materials, are of far-reaching significance. This review aims to provide new insights into developing the utilization of tea residue using a comprehensive strategy and exploring the mechanism of active components from tea residue on human health and their potential applications in different areas.HighlightsThe composition and function of tea residue active components were introduced.The extraction methods of active components from tea residue were proposed.The main high-value applications of tea residues were summarized.The current limitations and future directions of tea residue utilization were concluded.

Artemisinin and Its Derivate Alleviate Pulmonary Hypertension and Vasoconstriction in Rodent Models.

Background: Pulmonary arterial hypertension (PAH) is a complex pulmonary vasculature disease characterized by progressive obliteration of small pulmonary arteries and persistent increase in pulmonary vascular resistance, resulting in right heart failure and death if left untreated. Artemisinin (ARS) and its derivatives, which are common antimalarial drugs, have been found to possess a broad range of biological effects. Here, we sought to determine the therapeutic benefit and mechanism of ARS and its derivatives treatment in experimental pulmonary hypertension (PH) models. Methods: Isolated perfused/ventilated lung and isometric tension measurements in arteries were performed to test pulmonary vasoconstriction and relaxation. Monocrotaline (MCT) and hypoxia+Su5416 (SuHx) were administered to rats to induce severe PH. Evaluation methods of ARS treatment and its derivatives in animal models include echocardiography, hemodynamics measurement, and histological staining. In vitro, the effect of these drugs on proliferation, viability, and hypoxia-inducible factor 1α (HIF1α) was examined in human pulmonary arterial smooth muscle cells (hPASMCs). Results: ARS treatment attenuated pulmonary vasoconstriction induced by high K+ solution or alveolar hypoxia, decreased pulmonary artery (PA) basal vascular tension, improved acetylcholine- (ACh-) induced endothelial-dependent relaxation, increased endothelial nitric oxide (NO) synthase (eNOS) activity and NO levels, and decreased levels of NAD(P)H oxidase subunits (NOX2 and NOX4) expression, NAD(P)H oxidase activity, and reactive oxygen species (ROS) levels of pulmonary arteries (PAs) in MCT-PH rats. NOS inhibitor, L-NAME, abrogated the effects of ARS on PA constriction and relaxation. Furthermore, chronic application of both ARS and its derivative dihydroartemisinin (DHA) attenuated right ventricular systolic pressure (RVSP), Fulton index (right ventricular hypertrophy), and vascular remodeling of PAs in the two rat PH models. In addition, DHA inhibited proliferation and migration of hypoxia-induced PASMCs. Conclusions: In conclusion, these results indicate that treatment with ARS or DHA can inhibit PA vasoconstriction, PASMC proliferation and migration, and vascular remodeling, as well as improve PA endothelium-dependent relaxation, and eventually attenuate the development and progression of PH. These effects might be achieved by decreasing NAD(P)H oxidase generated ROS production and increasing eNOS activation to release NO in PAs. ARS and its derivatives might have the potential to be novel drugs for the treatment of PH.

A highly powerful nonspecific strategy to reduce COVID-19 deaths.

The coronavirus disease 2019 (COVID-19) pandemic caused by the coronavirus severe acute respiratory syndrome coronavirus 2 remains risky worldwide. We elucidate here that good IDM (isolation, disinfection, and maintenance of health) is powerful to reduce COVID-19 deaths based on the striking differences in COVID-19 case fatality rates among various scenarios. IDM means keeping COVID-19 cases away from each other and from other people, disinfecting their living environments, and maintaining their health through good nutrition, rest, and treatment of symptoms and pre-existing diseases (not through specific antiviral therapy). Good IDM could reduce COVID-19 deaths by more than 85% in 2020 and more than 99% in 2022. This is consistent with the fact that good IDM can minimize co-infections and maintain body functions and the fact that COVID-19 has become less pathogenic (this fact was supported with three novel data in this report). Although IDM has been frequently implemented worldwide to some degree, IDM has not been highlighted sufficiently. Good IDM is relative, nonspecific, flexible, and feasible in many countries, and can reduce deaths of some other relatively mild infectious diseases. IDM, vaccines, and antivirals aid each other to reduce COVID-19 deaths. The IDM concept and strategy can aid people to improve their health behavior and fight against COVID-19 and future pandemics worldwide.

Preparation, Physicochemical and Hypoglycemic Properties of Natural Selenium-Enriched Coarse Tea Glycoproteins.

Various functional components in tea have been well developed, but less research has been explored on glycoproteins in tea. In this paper, three types of glycoprotein fractions, namely tea selenium-binding glycoprotein1-1 (TSBGP1-1), TSBGP2-1, and TSBGP3-1, respectively, were extracted and purified from selenium-enriched coarse green tea. Chemical analysis revealed that three fractions were glycoproteins, but their selenium content, molecular weight, and monosaccharide composition were significantly different. Fourier transforms infrared (FT-IR) analysis indicated that three fractions contained characteristic absorption peaks of glycoproteins but differed in secondary structural composition. Thermogravimetric (TG) analysis showed that the thermal stability of the three fractions was dramatically distinct. The in vitro hypoglycemic activity showed that TSBGPs significantly activated the insulin receptor substrate 2 (IRS2)/protein kinase B (Akt) pathway in LO2 cells, then enhanced glucose metabolism and inhibited gluconeogenesis, and finally ameliorated insulin resistance (IR) and glucose metabolism disorders. Furthermore, Pearson correlation analysis reveals that the hypoglycemic activity was significantly correlated with Se, protein, monosaccharide composition (especially glucose), molecular weight, and secondary structure. Our results show that Se-enriched tea glycoprotein is a desirable candidate for developing anti-diabetic food, and TSBGP-2 and TSBGP-3 had a better regulation effect. Our results can provide a research reference for the extraction, physicochemical property, and function of selenium-enriched plant glycoproteins.

Extracellular vesicles derived from endothelial cells in hypoxia contribute to pulmonary artery smooth muscle cell proliferation in-vitro and pulmonary hypertension in mice.

In the lung, communication between pulmonary vascular endothelial cells (PVEC) and pulmonary artery smooth muscle cells (PASMC) is essential for the maintenance of vascular homeostasis. In pulmonary hypertension (PH), the derangement in their cell-cell communication plays a major role in the pathogenesis of pulmonary vascular remodeling. In this study, we focused on the role of PVEC-derived extracellular vesicles (EV), specifically their microRNA (miRNA, miR-) cargo, in the regulation of PASMC proliferation and vascular remodeling in PH. We found that the amount of pro-proliferative miR-210-3p was increased in PVEC-derived EV in hypoxia (H-EV), which contributes to the H-EV-induced proliferation of PASMC and the development of PH.