Selective permeation up a chemical potential gradient to enable an unusual solvent purification modality.

The need for energy-efficient recovery of organic solutes from aqueous streams is becoming more urgent as chemical manufacturing transitions toward nonconventional and bio-based feedstocks and processes. In addition to this, many aqueous waste streams contain recalcitrant organic contaminants, such as pharmaceuticals, industrial solvents, and personal care products, that must be removed prior to reuse. We observe that rigid carbon membrane materials can remove and concentrate organic contaminants via an unusual liquid-phase membrane permeation modality. Surprisingly, detailed thermodynamic calculations on the chemical potential of the organic contaminant reveal that the organic species has a higher chemical potential on the permeate side of the membrane than on the feed side of the membrane. This unusual observation challenges conventional membrane transport theory that posits that all permeating species move from high chemical potential states to lower chemical potential states. Based on experimental measurements, we hypothesize that the organic is concentrated in the membrane relative to water via favorable binding interactions between the organic and the carbon membrane. The concentrated organic is then swept through the membrane via the bulk flow of water in a modality known as "sorp-vection." We highlight via simplified nonequilibrium thermodynamic models that this "uphill" chemical potential permeation of the organic does not result in second-law violations and can be deduced via measurements of the organic and water sorption and diffusion rates into the carbon membrane. Moreover, this work identifies the need to consider such nonidealities when incorporating unique, rigid materials for the separations of aqueous waste streams.

Insertion of CO2 in metal ion-doped two-dimensional covalent organic frameworks.

Carbon capture is one of the essential low-carbon technologies required to achieve societal climate goals at the lowest cost. Covalent organic frameworks (COFs) are promising adsorbents for CO2 capture because of their well-defined porosity, large surface area, and high stability. Current COF-based CO2 capture is mainly based on a physisorption mechanism, exhibiting smooth and reversible sorption isotherms. In the present study, we report unusual CO2 sorption isotherms featuring one or more tunable hysteresis steps with metal ion (Fe3+, Cr3+, or In3+)-doped Schiff-base two-dimensional (2D) COFs (Py-1P, Py-TT, and Py-Py) as adsorbents. Synchrotron X-ray diffraction, spectroscopic and computational studies indicate that the sharp adsorption steps in the isotherm originate from the insertion of CO2 between the metal ion and the N atom of the imine bond on the inner pore surface of the COFs as the CO2 pressure reaches threshold values. As a result, the CO2 adsorption capacity of the ion-doped Py-1P COF is increased by 89.5% compared with that of the undoped Py-1P COF. This CO2 sorption mechanism provides an efficient and straightforward approach to enhancing the CO2 capture capacity of COF-based adsorbents, yielding insights into developing chemistry for CO2 capture and conversion.

Kaempferol attenuates particle-induced osteogenic impairment by regulating ER stress via the IRE1α-XBP1s pathway.

Periprosthetic osteolysis and subsequent aseptic loosening are the primary causes of failure following total joint arthroplasty. Wear particle-induced osteogenic impairment is recognized as an important contributing factor in the development of osteolysis, with endoplasmic reticulum (ER) stress emerging as a pivotal underlying mechanism. Hence, searching for potential therapeutic targets and agents capable of modulating ER stress in osteoblasts is crucial for preventing aseptic loosening. Kaempferol (KAE), a natural flavonol compound, has shown promising osteoprotective effects and anti-ER stress properties in diverse diseases. However, the influence of KAE on ER stress-mediated osteogenic impairment induced by wear particles remains unclear. In this study, we observed that KAE effectively relieved TiAl6V4 particles-induced osteolysis by improving osteogenesis in a mouse calvarial model. Furthermore, we demonstrated that KAE could attenuate ER stress-mediated apoptosis in osteoblasts exposed to TiAl6V4 particles, both in vitro and in vivo. Mechanistically, our results revealed that KAE mitigated ER stress-mediated apoptosis by upregulating the IRE1α-XBP1s pathway while concurrently partially inhibiting the IRE1α-regulated RIDD and JNK activation. Collectively, our findings suggest that KAE is a prospective therapeutic agent for treating wear particle-induced osteolysis and highlight the IRE1α-XBP1s pathway as a potential therapeutic target for preventing aseptic loosening.

Human Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Alleviate Hypoxia-Induced Pulmonary Arterial Hypertension in Mice Via Macrophages.

Pulmonary hypertension (PH) is an intractable, severe, and progressive cardiopulmonary disease. Recent findings suggest that human umbilical cord mesenchymal stromal cells (HUCMSCs) and HUCMSC-derived exosomes (HUCMSC-Exos) possess potential therapeutic value for PH. However, whether they have beneficial effects on hypoxic pulmonary hypertension (HPH) is unclear. Exos are released into the extracellular environment by the fusion of intracellular multivesicular bodies with the cell membrane, and they play an important role in cellular communication. Exos ameliorate immune inflammation levels, alter macrophage phenotypes, regulate mitochondrial metabolic function, and inhibit pulmonary vascular remodeling, thereby improving PH. Macrophages are important sources of cytokines and other transmitters and can promote the release of cytokines, vasoactive molecules, and reactive oxygen species, all of which are associated with pulmonary vascular remodeling. Therefore, the aim of this study was to investigate whether HUCMSC-Exos could improve the lung inflammatory microenvironment and inhibit pulmonary vascular remodeling by targeting macrophages and identifying the underlying mechanisms. The results showed that HUCMSC-Exos promoted M2 macrophage polarization, decreased pro-inflammatory factors, increased IL-10 levels, and inhibited IL-33/ST2 axis expression, thereby inhibiting hypoxia-induced proliferation of pulmonary artery smooth muscle cells and ameliorating HPH.

Tibetan Mesenchymal Stem Cell-derived Exosomes Alleviate Pulmonary Vascular Remodeling in Hypoxic Pulmonary Hypertension Rats.

Hypoxic pulmonary hypertension (HPH) is characterized by progressive pulmonary vasoconstriction, vascular remodeling, and right ventricular hypertrophy, causing right heart failure. This study aimed to investigate the therapeutic effects of exosomes from Tibetan umbilical cord mesenchymal stem cells on HPH via the TGF-ß1/Smad2/3 pathway, comparing them with exosomes from Han Chinese individuals. An HPH rat model was established in vivo, and a hypoxia-induced injury in the rat pulmonary artery smooth muscle cells (rPASMCs) was simulated in vitro. Exosomes from human umbilical cord mesenchymal stem cells were administered to HPH model rats or added to cultured rPASMCs. The therapeutic effects of Tibetan-mesenchymal stem cell-derived exosomes (Tibetan-MSC-exo) and Han-mesenchymal stem cell-derived exosomes (Han-MSC-exo) on HPH were investigated through immunohistochemistry, Western blotting, EdU, and Transwell assays. The results showed that Tibetan-MSC-exo significantly attenuated pulmonary vascular remodeling and right ventricular hypertrophy in HPH rats compared with Han-MSC-exo. Tibetan-MSC-exo demonstrated better inhibition of hypoxia-induced rPASMCs proliferation and migration. Transcriptome sequencing revealed upregulated genes (Nbl1, Id2, Smad6, and Ltbp1) related to the TGFß pathway. Nbl1 knockdown enhanced hypoxia-induced rPASMCs proliferation and migration, reversing Tibetan-MSC-exo-induced downregulation of TGFß1 and p-Smad2/3. Furthermore, TGFß1 overexpression hindered the therapeutic effects of Tibetan-MSC-exo and Han-MSC-exo on hypoxic injury. These findings suggest that Tibetan-MSC-exo favors HPH treatment better than Han-MSC-exo, possibly through the modulation of the TGFß1/Smad2/3 pathway via Nbl1.

Gate-Tunable Quantum Acoustoelectric Transport in Graphene.

Transport probes the motion of quasi-particles in response to external excitations. Apart from the well-known electric and thermoelectric transport, acoustoelectric transport induced by traveling acoustic waves has rarely been explored. Here, by adopting hybrid nanodevices integrated with piezoelectric substrates, we establish a simple design of acoustoelectric transport with gate tunability. We fabricate dual-gated acoustoelectric devices based on hBN-encapsulated graphene on LiNbO3. Longitudinal and transverse acoustoelectric voltages are generated by launching a pulsed surface acoustic wave. The gate dependence of zero-field longitudinal acoustoelectric signal presents strikingly similar profiles to that of Hall resistivity, providing a valid approach for extracting carrier density without magnetic field. In magnetic fields, acoustoelectric quantum oscillations appear due to Landau quantization, which are more robust and pronounced than Shubnikov-de Haas oscillations. Our work demonstrates a feasible acoustoelectric setup with gate tunability, which can be extended to the broad scope of various van der Waals materials.

MFSynDCP: multi-source feature collaborative interactive learning for drug combination synergy prediction.

Drug combination therapy is generally more effective than monotherapy in the field of cancer treatment. However, screening for effective synergistic combinations from a wide range of drug combinations is particularly important given the increase in the number of available drug classes and potential drug-drug interactions. Existing methods for predicting the synergistic effects of drug combinations primarily focus on extracting structural features of drug molecules and cell lines, but neglect the interaction mechanisms between cell lines and drug combinations. Consequently, there is a deficiency in comprehensive understanding of the synergistic effects of drug combinations. To address this issue, we propose a drug combination synergy prediction model based on multi-source feature interaction learning, named MFSynDCP, aiming to predict the synergistic effects of anti-tumor drug combinations. This model includes a graph aggregation module with an adaptive attention mechanism for learning drug interactions and a multi-source feature interaction learning controller for managing information transfer between different data sources, accommodating both drug and cell line features. Comparative studies with benchmark datasets demonstrate MFSynDCP's superiority over existing methods. Additionally, its adaptive attention mechanism graph aggregation module identifies drug chemical substructures crucial to the synergy mechanism. Overall, MFSynDCP is a robust tool for predicting synergistic drug combinations. The source code is available from GitHub at https://github.com/kkioplkg/MFSynDCP .

Rapidly mining candidate cotton drought resistance genes based on key indicators of drought resistance.

BACKGROUND: Focusing on key indicators of drought resistance is highly important for quickly mining candidate genes related to drought resistance in cotton. RESULTS: In the present study, drought resistance was identified in drought resistance-related RIL populations during the flowering and boll stages, and multiple traits were evaluated; these traits included three key indicators: plant height (PH), single boll weight (SBW) and transpiration rate (Tr). Based on these three key indicators, three groups of extreme mixing pools were constructed for BSA-seq. Based on the mapping interval of each trait, a total of 6.27 Mb QTL intervals were selected on chromosomes A13 (3.2 Mb), A10 (2.45 Mb) and A07 (0.62 Mb) as the focus of this study. Based on the annotation information and qRT‒PCR analysis, three key genes that may be involved in the drought stress response of cotton were screened: GhF6'H1, Gh3AT1 and GhPER55. qRT‒PCR analysis of parental and extreme germplasm materials revealed that the expression of these genes changed significantly under drought stress. Cotton VIGS experiments verified the important impact of key genes on cotton drought resistance. CONCLUSIONS: This study focused on the key indicators of drought resistance, laying the foundation for the rapid mining of drought-resistant candidate genes in cotton and providing genetic resources for directed molecular breeding of drought resistance in cotton.

A facile Immunoregulatory Constructional Design by Proanthocyanidin Optimizing Directional Chitosan Microchannel.

Improving the interconnected structure and bioregulatory function of natural chitosan is beneficial for optimizing its performance in bone regeneration. Here, a facile immunoregulatory constructional design is proposed for developing instructive chitosan by directional freezing and alkaline salting out. The molecular dynamics simulation confirmed the assembly kinetics and structural features of various polyphenols and chitosan molecules. Along with the in vitro anti-inflammatory, antioxidative, promoting bone mesenchymal stem cell (BMSC) adhesion and proliferation performance, proanthocyanidin optimizing chitosan (ChiO) scaffold presented an optimal immunoregulatory structure with the directional microchannel. Transcriptome analysis in vitro further revealed the cytoskeleton- and immune-regulation effect of ChiO are the key mechanism of action on BMSC. The rabbit cranial defect model (Φ = 10 mm) after 12 weeks of implantation confirmed the significantly enhanced bone reconstitution. This facile immunoregulatory directional microchannel design provides effective guidance for developing inducible chitosan scaffolds.

Topological Lifshitz transition and one-dimensional Weyl mode in HfTe5.

Landau band crossings typically stem from the intra-band evolution of electronic states in magnetic fields and enhance the interaction effect in their vicinity. Here in the extreme quantum limit of topological insulator HfTe5, we report the observation of a topological Lifshitz transition from inter-band Landau level crossings using magneto-infrared spectroscopy. By tracking the Landau level transitions, we demonstrate that band inversion drives the zeroth Landau bands to cross with each other after 4.5 T and forms a one-dimensional Weyl mode with the fundamental gap persistently closed. The unusual reduction of the zeroth Landau level transition activity suggests a topological Lifshitz transition at 21 T, which shifts the Weyl mode close to the Fermi level. As a result, a broad and asymmetric absorption feature emerges due to the Pauli blocking effect in one dimension, along with a distinctive negative magneto-resistivity. Our results provide a strategy for realizing one-dimensional Weyl quasiparticles in bulk crystals.

Covalent organic framework atropisomers with multiple gas-triggered structural flexibilities.

Covalent organic frameworks (COFs) are emerging crystalline porous polymers, showing great potential for applications but lacking gas-triggered flexibility. Atropisomerism was experimentally discovered in 1922 but has rarely been found in crystals with infinite framework structures. Here we report atropisomerism in COF single crystals. The obtained COF atropisomers, namely COF-320 and COF-320-A, have identical chemical and interpenetrated structures but differ in the spatial arrangement of repeating units. In contrast to the rigid COF-320 structure, its atropisomer (COF-320-A) exhibits unconventional gas sorption behaviours with one or more sorption steps in isotherms at different temperatures. Single-crystal structures determined from continuous rotation electron diffraction and in situ powder X-ray diffraction demonstrate that these adsorption steps originate from internal pore expansion with or without changing the crystal space group. COF-320-A recognizes different gases by expanding its internal pores continuously (crystal-to-amorphous transition) or discontinuously (crystal-to-crystal transition) or having mixed transition styles, distinguishing COF-320-A from existing soft/flexible porous crystals. These findings extend atropisomerism from molecules to crystals and propel COFs into the covalently linked soft porous crystal regime, further advancing applications of soft porous crystals in gas sorption, separation and storage.

A Deep Learning-Based System Trained for Gastrointestinal Stromal Tumor Screening Can Identify Multiple Types of Soft Tissue Tumors.

The accuracy and timeliness of the pathologic diagnosis of soft tissue tumors (STTs) critically affect treatment decision and patient prognosis. Thus, it is crucial to make a preliminary judgement on whether the tumor is benign or malignant with hematoxylin and eosin-stained images. A deep learning-based system, Soft Tissue Tumor Box (STT-BOX), is presented herein, with only hematoxylin and eosin images for malignant STT identification from benign STTs with histopathologic similarity. STT-BOX assumed gastrointestinal stromal tumor as a baseline for malignant STT evaluation, and distinguished gastrointestinal stromal tumor from leiomyoma and schwannoma with 100% area under the curve in patients from three hospitals, which achieved higher accuracy than the interpretation of experienced pathologists. Particularly, this system performed well on six common types of malignant STTs from The Cancer Genome Atlas data set, accurately highlighting the malignant mass lesion. STT-BOX was able to distinguish ovarian malignant sex-cord stromal tumors without any fine-tuning. This study included mesenchymal tumors that originated from the digestive system, bone and soft tissues, and reproductive system, where the high accuracy of migration verification may reveal the morphologic similarity of the nine types of malignant tumors. Further evaluation in a pan-STT setting would be potential and prospective, obviating the overuse of immunohistochemistry and molecular tests, and providing a practical basis for clinical treatment selection in a timely manner.

Stability-enhanced low-frequency fiber optic hydrophone based on an extrinsic Fabry-Perot interferometer.

Fiber optic hydrophones (FOHs) offer the notable advantage of electromagnetic interference resistance. Nevertheless, overcoming the challenge of sustaining stable, high-performance operation in intricate underwater settings at a low cost remains a considerable obstacle for them. To circumvent the restrictions noted above, we employed a miniaturized FOH, utilizing an easily fabricated extrinsic Fabry-Perot interferometer (EFPI) which is made up of a composite chromium-aluminum (Cr-Al) membrane and fiber. The linear demodulation also suppresses the drift issue in the output spectrum. The average sound pressure sensitivity of the sensor, according to experimental findings, is around -139.15 dB re 1 V/µPa, while the equivalent noise sound pressure at 1 kHz is 51.52 dB re 1 µPa/Hz1/2. This sensor has a lot of potential because of features like sensitive low-frequency response and noise performance.

Predicted Separation of Acid Gases from Gas Mixtures by Functionalized Porous Aromatic Frameworks.

The selective adsorption of target acid gas molecules from binary gas mixtures by porous aromatic frameworks (PAFs) with two identical functional groups per aromatic ring (PAF-R2) was computationally investigated using grand canonical Monte Carlo simulations. PAF-R2 adsorption was considered for three binary mixtures of small molecular concentrations of acid gas and abundant nitrogen gas (CO2/N2, SO2/N2, and H2S/N2). The results indicate that additional functional groups enhance acid gas loadings and selectivity, compared with pristine PAF and single-functionalized PAFs. Low pressures yield linearly increasing gas loadings and constant selectivity, while high pressures yield much higher adsorption and selectivity. In particular, SO2 loading and selectivity under high pressures are heavily influenced by the PAF's maximum adsorption limit, which can be linked back to the functional groups and their configuration. In summary, PAF-(3,5)-(COOH)2 (nomenclature of PAFs is provided in the Appendix in the Supporting Information) and many other PAF with the same two electron-withdrawing groups are predicted to have great acid gas adsorption and selectivity from gas mixtures, while PAF-(3,5)-(OH)2 (one of PAFs with two identical electron-donating groups) is predicted to have good adsorption and selectivity, especially under elevated pressures. The results of this work can provide insights into various types of PAFs with great selective adsorption ability and their corresponding conditions. The simulation procedures and results may inspire the exploration and screening of other types of PAFs or porous materials, for acid gas absorption.

C9-Aryl-substituted berberine derivatives with tunable AIE properties for cell imaging application.

Berberine (BBR), a widely used isoquinoline alkaloid derived from natural sources, exhibits aggregation-induced emission (AIE) characteristics and has biological applications such as in selective lipid droplet imaging and photodynamic therapy. However, natural BBR suffers from low fluorescence quantum yield (ΦF) and monotonous emission wavelength. In this paper, a series of C9-position-aryl-substituted berberine derivatives with a D-A structure were designed and synthesized. The electronic effect of the substitution groups can tune the intramolecular charge transfer (ICT) effect of the berberine derivatives, resulting in bluish green to NIR (508-682 nm) luminescence with AIE characteristics and enhanced ΦF up to 36% in the solid state. Interestingly, berberine derivatives containing an amino or a pyridyl group can exhibit fluorescence response to TFA. Cell imaging of the berberine derivatives was conducted using Caco-2 cancer cells, demonstrating their multi-color and efficient wash-free imaging capabilities. This work presents a new strategy for developing novel berberine derivatives with tunable AIE properties for application in biological imaging.

HBCalculator: A Tool for Hydrogen Bond Distribution Calculations in Molecular Dynamics Simulations.

Hydrogen bonds, crucial noncovalent interactions in molecular systems, significantly impact biological, chemical, and energy-related processes; therefore, characterizing hydrogen bond information is of importance to fundamental studies. This work introduces the HBCalculator, a Tcl-based tool integrated with VMD for calculating 1D and 2D distributions of hydrogen bond density and strength. The tool facilitates spatial analysis, overcoming limitations in existing packages that lack direct spatial distribution output. By employing HBCalculator in MD simulations, three systems of cellulose/water and graphene/water interfaces, were tested to showcase its functionality. The 1D and 2D hydrogen bond distributions reveal insights into interfacial properties, reflecting the impact of material hydrophobicity. The simplicity of usage, along with its potential for diverse molecular systems, positions HBCalculator as a valuable tool for researchers exploring hydrogen bond networks.

Associations of dietary inflammatory index with low estimated glomerular filtration rate, albuminuria and chronic kidney disease in U.S adults: Results from the NHANES 2011-2018.

BACKGROUND AND AIMS: Chronic Kidney Disease (CKD) is characterized by a high inflammation status with ever-increasing prevalence, and defined as low estimated glomerular filtration rate (eGFR) or albuminuria. Both low eGFR and albuminuria can have independent effects on the body. The dietary inflammatory index (DII) is a validated tool used to assess the inflammatory potential of the diet. We aim to explore not only the association between DII and CKD, but also the associations of DII with low eGFR and albuminuria, respectively. In addition, their associations in different subgroups remain to be explored. METHODS AND RESULTS: 18,070 participants from the 2011-2018 NHANES with complete data of dietary intake and laboratory data were involved in our study. The data of 24-hour dietary recall interview was used to calculate DII, CKD could be reflected by laboratory data of creatinine and albumin. Then weighted multivariate logistic regression models and subgroup analyses were performed. The prevalence of low eGFR, albuminuria and CKD were 6.8%, 9.8% and 14.5%, respectively. A positive association between DII and low eGFR was observed (OR=1.12, 95%CI: 1.05-1.21), Q2, Q3 and Q4 are positively associated with a significant 39%, 65% and 71% increased risk of low eGFR compared with Q1 (P for trend<0.05). DII was also associated with CKD (OR=1.06, 95%CI: 1.01-1.11). CONCLUSION: Significant positive associations of DII with CKD and low eGFR were observed. But we didn't find such association between DII and albuminuria.

YY1 safeguard multidimensional epigenetic landscape associated with extended pluripotency.

Although extended pluripotent stem cells (EPSCs) have the potential to form both embryonic and extraembryonic lineages, how their transcriptional regulatory mechanism differs from that of embryonic stem cells (ESCs) remains unclear. Here, we discovered that YY1 binds to specific open chromatin regions in EPSCs. Yy1 depletion in EPSCs leads to a gene expression pattern more similar to that of ESCs than control EPSCs. Moreover, Yy1 depletion triggers a series of epigenetic crosstalk activities, including changes in DNA methylation, histone modifications and high-order chromatin structures. Yy1 depletion in EPSCs disrupts the enhancer-promoter (EP) interactions of EPSC-specific genes, including Dnmt3l. Yy1 loss results in DNA hypomethylation and dramatically reduces the enrichment of H3K4me3 and H3K27ac on the promoters of EPSC-specific genes by upregulating the expression of Kdm5c and Hdac6 through facilitating the formation of CCCTC-binding factor (CTCF)-mediated EP interactions surrounding their loci. Furthermore, single-cell RNA sequencing (scRNA-seq) experiments revealed that YY1 is required for the derivation of extraembryonic endoderm (XEN)-like cells from EPSCs in vitro. Together, this study reveals that YY1 functions as a key regulator of multidimensional epigenetic crosstalk associated with extended pluripotency.

Ideal cardiovascular health metrics have better identification of arthritis.

BACKGROUND: This study aimed to explore the association between ideal cardiovascular health metrics (ICVHM) and arthritis (AR), as well as the interactions of various indicators in ICVHM on AR in US adults. METHODS: We involved 17,041 participants who were interviewed by NHANES from 2011 to 2018. AR included osteoarthritis or degenerative arthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis and other arthritis (Other AR). Logistic regression was applied to analyze the association between AR and ICVHM. Mixed graphical model (MGM) was used to explore the interaction between variables in ICVHM. RESULTS: Higher ICVHM scores had a protective effect on AR. Compared to "≤1" score, the ORs of AR in participants with 2, 3, 4, and ≥5 were 0.586, 0.472, 0.259, and 0.130, respectively. Similar results were also found in different types of AR. ICVHM has a maximum area under the curve value of 0.765 and the interaction between blood pressure and total cholesterol was 0.43. CONCLUSIONS: ICVHM correlates significantly with AR and is better at identifying AR than individual indicators. ICVHM can be better improved by controlling the indicators with stronger interactions. Our findings provide guidance for promoting health factors, which have important implications for identification and prevention of AR.

[Effects of human umbilical cord mesenchymal stem cells (MSCs)-derived exosomes on pulmonary vascular remodeling in hypoxic pulmonary hypertension].

The present study aimed to investigate the effect of human umbilical cord mesenchymal stem cells (MSCs)-derived exosomes (MSCs-Exo) on mice with hypoxic pulmonary hypertension (HPH). MSCs were isolated and cultured from human umbilical cords under aseptic conditions, and exosomes were extracted from the supernatants and identified. Healthy SPF C57BL/6 mice were randomly divided into three groups: normoxic group, hypoxic group, and hypoxic+MSCs-Exo group. Mice in the hypoxic group and the hypoxic+MSCs-Exo group were maintained for 28 d at an equivalent altitude of 5 000 m in a hypobaric chamber to establish HPH mouse model. The mice in the hypoxic+MSCs-Exo group were injected with MSCs-Exo via tail vein before hypoxia and on days 1, 3, 5 and 9 of hypoxia, and the mice in the other two groups were injected with PBS. At the end of the experiment, echocardiography was performed to detect pulmonary arterial acceleration time/pulmonary arterial ejection time ratio (PAAT/PET), right ventricular free wall thickness, and right ventricular hypertrophy index RV/(LV+S). HE staining was performed to observe the lung tissue morphology. EVG staining was performed to observe elastic fiber hyperplasia. Immunohistochemistry was performed to detect α smooth muscle actin (α-SMA) expression in lung tissue. Immunofluorescence staining was used to detect macrophage infiltration in lung tissue. qPCR was performed to detect IL-1ß and IL-33 in lung tissue, and cytometric bead array was performed to detect IL-10 secretion. Western blotting was used to detect the M1 macrophage marker iNOS, M2 macrophage marker Arg-1 and IL-33/ST2 pathway proteins in lung tissues. The results showed that hypoxia increased pulmonary artery pressure and pulmonary vascular remodeling, increased macrophage infiltration, IL-1ß and IL-33 expression (P < 0.05) and upregulated the IL-33/ST2 pathway (P < 0.05). Compared with the hypoxic group, MSCs-Exo treatment increased PAAT/PET (P < 0.05), decreased right ventricular free wall thickness (P < 0.05), right ventricular hypertrophy index RV/(LV+S) (P < 0.05), α-SMA expression in small pulmonary vessels (P < 0.05), and inflammatory factors including IL-1ß and IL-33 expression in lung tissue, however increased IL-10 secretion (P < 0.05). In addition, MSCs-Exo treatment upregulated Arg-1 and downregulated iNOS and IL-33/ST2 (P < 0.05). The results suggest that MSC-Exo may alleviate HPH through their immunomodulatory effects.