Minimal and hybrid hydrogenases are active from archaea.

Microbial hydrogen (H2) cycling underpins the diversity and functionality of diverse anoxic ecosystems. Among the three evolutionarily distinct hydrogenase superfamilies responsible, [FeFe] hydrogenases were thought to be restricted to bacteria and eukaryotes. Here, we show that anaerobic archaea encode diverse, active, and ancient lineages of [FeFe] hydrogenases through combining analysis of existing and new genomes with extensive biochemical experiments. [FeFe] hydrogenases are encoded by genomes of nine archaeal phyla and expressed by H2-producing Asgard archaeon cultures. We report an ultraminimal hydrogenase in DPANN archaea that binds the catalytic H-cluster and produces H2. Moreover, we identify and characterize remarkable hybrid complexes formed through the fusion of [FeFe] and [NiFe] hydrogenases in ten other archaeal orders. Phylogenetic analysis and structural modeling suggest a deep evolutionary history of hybrid hydrogenases. These findings reveal new metabolic adaptations of archaea, streamlined H2 catalysts for biotechnological development, and a surprisingly intertwined evolutionary history between the two major H2-metabolizing enzymes.

Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induced Autoimmunity.

The presence of DNA in the cytoplasm is normally a sign of microbial infections and is quickly detected by cyclic GMP-AMP synthase (cGAS) to elicit anti-infection immune responses. However, chronic activation of cGAS by self-DNA leads to severe autoimmune diseases for which no effective treatment is available yet. Here we report that acetylation inhibits cGAS activation and that the enforced acetylation of cGAS by aspirin robustly suppresses self-DNA-induced autoimmunity. We find that cGAS acetylation on either Lys384, Lys394, or Lys414 contributes to keeping cGAS inactive. cGAS is deacetylated in response to DNA challenges. Importantly, we show that aspirin can directly acetylate cGAS and efficiently inhibit cGAS-mediated immune responses. Finally, we demonstrate that aspirin can effectively suppress self-DNA-induced autoimmunity in Aicardi-Goutières syndrome (AGS) patient cells and in an AGS mouse model. Thus, our study reveals that acetylation contributes to cGAS activity regulation and provides a potential therapy for treating DNA-mediated autoimmune diseases.

Mapping the Mouse Cell Atlas by Microwell-Seq.

Single-cell RNA sequencing (scRNA-seq) technologies are poised to reshape the current cell-type classification system. However, a transcriptome-based single-cell atlas has not been achieved for complex mammalian systems. Here, we developed Microwell-seq, a high-throughput and low-cost scRNA-seq platform using simple, inexpensive devices. Using Microwell-seq, we analyzed more than 400,000 single cells covering all of the major mouse organs and constructed a basic scheme for a mouse cell atlas (MCA). We reveal a single-cell hierarchy for many tissues that have not been well characterized previously. We built a web-based "single-cell MCA analysis" pipeline that accurately defines cell types based on single-cell digital expression. Our study demonstrates the wide applicability of the Microwell-seq technology and MCA resource.

Controlled flight of a microrobot powered by soft artificial muscles.

Flying insects capable of navigating in highly cluttered natural environments can withstand in-flight collisions because of the combination of their low inertia1 and the resilience of their wings2, exoskeletons1 and muscles. Current insect-scale (less than ten centimetres long and weighing less than five grams) aerial robots3-6 use rigid microscale actuators, which are typically fragile under external impact. Biomimetic artificial muscles7-10 that are capable of large deformation offer a promising alternative for actuation because they can endure the stresses caused by such impacts. However, existing soft actuators11-13 have not yet demonstrated sufficient power density to achieve lift-off, and their actuation nonlinearity and limited bandwidth create further challenges for achieving closed-loop (driven by an input control signal that is adjusted based on sensory feedback) flight control. Here we develop heavier-than-air aerial robots powered by soft artificial muscles that demonstrate open-loop (driven by a predetermined signal without feedback), passively stable (upright during flight) ascending flight as well as closed-loop, hovering flight. The robots are driven by multi-layered dielectric elastomer actuators that weigh 100 milligrams each and have a resonance frequency of 500 hertz and power density of 600 watts per kilogram. To increase the mechanical power output of the actuator and to demonstrate flight control, we present ways to overcome challenges unique to soft actuators, such as nonlinear transduction and dynamic buckling. These robots can sense and withstand collisions with surrounding obstacles and can recover from in-flight collisions by exploiting material robustness and vehicle passive stability. We also fly two micro-aerial vehicles simultaneously in a cluttered environment. They collide with the wall and each other without suffering damage. These robots rely on offboard amplifiers and an external motion-capture system to provide power to the dielectric elastomer actuators and to control their flight. Our work demonstrates how soft actuators can achieve sufficient power density and bandwidth to enable controlled flight, illustrating the potential of developing next-generation agile soft robots.

Aluminum Halide-Based Electron-Selective Passivating Contacts for Crystalline Silicon Solar Cells.

Extensive research has focused on developing wide-bandgap metal compound-based passivating contacts as alternatives to conventional doped-silicon-layer-based passivating contacts to mitigate parasitic absorption losses in crystalline silicon (c-Si) solar cells. Herein, thermally-evaporated aluminum halides (AlX)-based electron-selective passivating contacts for c-Si solar cells are investigated. A low contact resistivity of 60.5 and 38.4 mΩ cm2 is obtained on the AlClx/n-type c-Si (n-Si) and AlFx/n-Si heterocontacts, respectively, thanks to the low work function of AlX. Power conversion efficiencies (PCEs) of 19.1% and 19.6% are achieved on proof-of-concept n-Si solar cells featuring a full-area AlClx/Al and AlFx/Al passivating contact, respectively. By further implementing an ultrathin SiO2 passivation interlayer and a pre-annealing treatment, the electron selectivity (especially the surface passivation) of AlX is significantly enhanced. Accordingly, a remarkable PCE of 21% is achieved on n-Si solar cells featuring a full-area SiO2/AlFx/Al rear contact. AlFx-based electron-selective passivating contacts exhibit good thermal stability up to ≈400 °C and better long-term environmental stability. This work demonstrates the potential of AlFx-based electron-selective passivating contact for solar cells.

Assessing the protection elicited by virus-like particles expressing the RSV pre-fusion F and tandem repeated G proteins against RSV rA2 line19F infection in mice.

Excessive pulmonary inflammation is the hallmark of respiratory syncytial virus (RSV) infection hindering efficacious RSV vaccine development. Yet, the vast majority of the experimental RSV vaccine studies use laboratory-adapted RSV strains that do not reflect the highly pathogenic and inflammatory nature of the virus found in clinical settings. Here, we re-evaluated the protective efficacy of the virus-like particle (VLP) vaccine co-expressing the pre-fusion (pre-F) protein and G protein with tandem repeats (Gt) reported in our previous study against the recombinant RSV rA2-line19F strain, which inflicts severe mucus production and inflammation in mice. VLP vaccine immunization elicited virus-specific serum antibody responses that mediated RSV rA2-line19F virus neutralization. VLP vaccine immunization promoted Th1 immune response development in the spleens and CD8 + T cell influx into the lungs of mice, which are essential for efficient viral clearance and dampened inflammatory response. When compared to the VLPs expressing only the pre-F antigen, those co-expressing both pre-F and Gt antigens conferred better protection in mice against rA2-line19F challenge infection. Overall, our data suggest that the pre-clinical VLP vaccine co-expressing RSV pre-F and Gt antigens can effectively protect mice against RSV strains that resemble pathogenic clinical isolates.

The stress granule protein G3BP1 promotes pre-condensation of cGAS to allow rapid responses to DNA.

Cyclic GMP-AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid-phase condensation state. Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre-condensed cGAS undergoes liquid-liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA-induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA - but not RNA - treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.

Efficient photoelectrocatalytic degradation of pollutants over hydrophobic carbon felt loaded with Fe-doped porous carbon nitride via direct activation of molecular oxygen.

Developing a photoelectric cathode capable of efficiently activating molecular oxygen to degrade pollutants is a coveted yet challenging goal. In pursuit of this, we synthesize a Fe doped porous carbon nitride catalyst (Fe-CN) using an ionothermal strategy and subsequently loaded it on the hydrophobic carbon felt (CF) to fabricate the Fe-CN/CF photoelectric cathode. This cathode benefits from the synergistic effects between the porous CN support and the highly dispersed Fe species, which enhance O2 absorption and activation. Additionally, the hydrophobic CF serves as a gas diffusion layer, accelerating O2 mass transfer. These features enable the Fe-CN/CF cathode to demonstrate notable photoelectrocatalytic (PEC) degradation efficiency. Specifically, under optimal conditions (cathodic bias of -0.3 VAg/AgCl, pH 7, and a catalyst loading of 3 mg/cm2), the system achieves a 76.4% removal rate of tetracycline (TC) within 60 min. The general application potential of this system is further underscored by its ability to remove approximately 98% of 4-chlorophenol (4-CP) and phenol under identical conditions. Subsequent investigations into the active species and degradation pathways reveal that 1O2 and h+ play dominant role during the PEC degradation process, leading to gradually breakdown of TC into less toxicity, smaller molecular intermediates. This work presents a straightforward yet effective strategy for constructing efficient PEC systems that leverage molecular oxygen activation to degrade pollutants.

Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma.

BACKGROUND: This study aimed to validate whether infusion of GD2-specific fourth-generation safety-designed chimeric antigen receptor (4SCAR)-T cells is safe and whether CAR-T cells exert anti-glioblastoma (GBM) activity. METHODS: A total of eight patients with GD2-positive GBM were enrolled and infused with autologous GD2-specific 4SCAR-T cells, either through intravenous administration alone or intravenous combined with intracavitary administration. RESULTS: 4SCAR-T cells expanded for 1-3 weeks and persisted at a low frequency in peripheral blood. Of the eight evaluable patients, four showed a partial response for 3 to 24 months, three had progressive disease for 6 to 23 months, and one had stable disease for 4 months after infusion. For the entire cohort, the median overall survival was 10 months from the infusion. GD2 antigen loss and infiltrated T cells were observed in the tumor resected after infusion. CONCLUSION: Both single and combined infusions of GD2-specific 4SCAR-T cells in targeting GBM were safe and well tolerated, with no severe adverse events. In addition, GD2-specific 4SCAR-T cells partially mediate antigen loss and activate immune responses in the tumor microenvironment. Validation of our findings in a larger prospective trial is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03170141 . Registered 30 May 2017.

G3BP1 Inhibition Alleviates Intracellular Nucleic Acid-Induced Autoimmune Responses.

The detection of intracellular nucleic acids is a fundamental mechanism of host defense against infections. The dysregulated nucleic acid sensing, however, is a major cause for a number of autoimmune diseases. In this study, we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for both intracellular DNA- and RNA-induced immune responses. We found that in both human and mouse cells, the deletion of G3BP1 led to the dampened cGAS activation by DNA and the insufficient binding of RNA by RIG-I. We further found that resveratrol (RSVL), a natural compound found in grape skin, suppressed both intracellular DNA- and RNA-induced type I IFN production through inhibiting G3BP1. Importantly, using experimental mouse models for Aicardi-Goutières syndrome, an autoimmune disorder found in humans, we demonstrated that RSVL effectively alleviated intracellular nucleic acid-stimulated autoimmune responses. Thus, our study demonstrated a broader role of G3BP1 in sensing different kinds of intracellular nucleic acids and presented RSVL as a potential treatment for autoimmune conditions caused by dysregulated nucleic acid sensing.

Polybutadiene Dielectric Elastomers with High Dielectric Constant and Ultralow Dielectric Loss via Tuning Grafted Polar Groups.

This work describes an easy and effective process for preparing a homogeneous polybutadiene (PB) dielectric elastomer with improved actuated strain by utilizing a photochemical thiol-ene click reaction. The carboxyl groups and various ester groups are used for grafting on the PB. Since the length of the alkyl chains of the ester groups will significantly influence the polarities of the carbonyl groups and hydrogen bonding effect, the influence of polarity and hydrogen bonding effect on the dielectric properties and mechanical properties of the modified polybutadienes is carefully discussed. Very interestingly, it is found that the increment of dielectric constant of PB modified by carboxyl groups is the lowest one compared to other modified PBs with the ester groups. Meanwhile, the modified PBs with the ester groups could achieve pretty low dielectric loss factor, and finally, a high dielectric constant (3.6), low dielectric loss factor (0.0005), and large actuated strain (≈25%) of the modified polybutadienes could be achieved by the modified PBs with butyl acrylate groups. This work provides a simple and effective method for the designing and synthesizing of a homogeneous high electromechanical performance dielectric elastomer with high dielectric constant and low dielectric loss.

Effects of graphitic carbon nitride in the formation of disinfection byproducts.

Graphitic carbon nitride (CN) was a promising candidate for efficient environmental remediation in the advanced oxidation processes (AOPs). However, whether CN itself had some potential environmental risks, such as affecting the production of disinfection byproducts (DBPs) was still unknown. This study investigated the formation potential of DBPs in the presence of CN. The experimental data revealed that CN had a high potential to form DBPs, and dichloroacetonitrile (DCAN) was the most produced species during the chlorination and chloramination processes. Moreover, the effects of chlorine time, chlorine dosage, pH, and CN dosage during the chlorination process were evaluated to understand the formation pattern of DBPs. The possible mechanism of DBPs formation was deduced by analyzing the results of FTIR, Raman, and XPS before and after chlorination. Finally, the DBPs formation potential and cytotoxicity of the CN leaching solution were investigated, indicating CN could leach the precursors of DBPs and that the potential toxicity of the leaching solution increased with the extension of CN immersion time. In general, this research adds an understanding of the DBP formation of CN in water treatment systems and sheds light on CN's environmental potential risks.

[Total triterpenes of Euphorbium alleviates rheumatoid arthritis via Nrf2/HO-1/GPX4 pathway].

This study aims to investigate the effect and mechanism of total triterpenes of Euphorbium in treating rheumatoid arthritis(RA). The rat model of RA was established with Freund's complete adjuvant(FCA). Male rats were randomly assigned into control, model, Tripterygium glycosides(7.5 mg·kg~(-1)), and low-, medium-, and high-dose total triterpenes of Euphorbium(32, 64, and 128 mg·kg~(-1), respectively) groups, with 10 rats in each group. In other groups except the control group, 0.2 mL FCA was injected into the right hind toe. Rats in the intervention groups were administrated with corresponding drugs by gavage, and the control group and the model group with the same volume of 0.5% CMC-Na solution once a day. During the treatment period, the swelling degree of the hind paw was measured and the arthritis was scored until day 30. At the end of drug administration, the pathological changes of the joint tissue were observed by hematoxylin-eosin staining. The content of malondialdehyde(MDA), glutathione(GSH), and Fe~(2+) and the activity of superoxide dismutase(SOD) in the joint tissue were measured by biochemical colorimetry. RT-PCR was performed to determine the mRNA levels of nuclear factor erythroid 2-related factor 2(Nrf2), glutathione peroxidase 4(GPX4), and acyl-CoA synthetase long chain family member 4(ACSL4) in the joint tissue. Western blot was employed to determine the protein levels of Nrf2, Kelch-like ECH-associated protein 1(Keap1), heme oxygenase-1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), SOD2, GPX4, and ACSL4 in the joint tissue. The results showed that the treatment with Tripterygium glycosides(7.5 mg·kg~(-1)) and total triterpenes of Euphorbium(32, 64, and 128 mg·kg~(-1)) alleviated the swelling degree of bilateral hind limbs, decreased the arthritis score, reduced joint tissue lesions and the content of MDA and Fe~(2+) in the joint tissue, and increased GSH content and SOD activity. Furthermore, the interventions up-regulated the protein and mRNA levels of Nrf2 and GPX4, down-regulated the protein and mRNA levels of ACSL4, and up-regulated the protein levels of Keap1, NQO1, HO-1, and SOD2 in the Nrf2/HO-1/GPX4. In summary, the total triterpenes of Euphorbium can treat RA by inhibiting lipid peroxidation and abnormal ferroptosis, which may involve the Nrf2/HO-1/GPX4 signaling pathway.

Comprehensive kinomic study via a chemical proteomic approach reveals kinome reprogramming in hepatocellular carcinoma tissues.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Kinases are attractive therapeutic targets since they are commonly altered in cancers. Here, to identify kinases of potential therapeutic interest in HCC, a quantitative kinomic study of tumour and adjacent non-tumour liver tissues was performed using a chemical proteomics approach. In total, 124 kinases were found differentially expressed and they were distributed over all nine kinase groups. Exploration of The Cancer Genome Atlas (TCGA) data showed that the dysregulation of 45 kinases was correlated with poor prognosis in HCC patients. We then tested 11 inhibitors targeting 12 crucial protein kinases alone or in combination for their ability to inhibit cell growth in Hep3B and PLC/PRF/5 cell lines. Six inhibitors significantly reduced viability in both cell lines. Combination inhibition of polo-like kinase 1 (PLK1) and casein kinase 1 epsilon (CSNK1E) significantly induced growth arrest in both cell lines synergistically. In summary, our analysis presents the most complete view of kinome reprogramming in HCC and provides novel insight into crucial kinases in HCC and potential therapeutic targets for HCC treatment. Moreover, the identification of hundreds of differentially expressed kinases forms a rich resource for novel drug targets or diagnostic biomarker discovery. Data are available via ProteomeXchange (identifier PXD023806).

EZH2 upregulates the expression of MAPK1 to promote intervertebral disc degeneration via suppression of miR-129-5p.

BACKGROUND: This study was designed to verify whether enhancer of zeste homolog 2 (EZH2) affects intervertebral disc degeneration (IVDD) development through regulation of microRNA (miR)-129-5p/MAPK1. METHODS: Initially, we collected lumbar nucleus pulposus (NP) tissue samples from patients with juvenile idiopathic scoliosis (n = 14) and IVDD (n = 34). We measured the expression of related genes in clinical IVDD tissues and a lipopolysaccharide (LPS)-induced NP cell model. After loss- and gain-of-function assays, NP cell proliferation and senescence were examined. The targeting relationship between miR-129-5p and MAPK1 was explored by dual luciferase reporter gene and RNA immunoprecipitation (RIP) assays. The enrichment of EZH2 and H3K27me3 in miR-129-5p promoter was verified by chromatin immunoprecipitation (ChIP). Finally, an IVDD rat model was established to test the effects of transduction with lentiviral vector carrying miR-129-5p agomir and/or oe-EZH2 in vivo. RESULTS: miR-129-5p was underexpressed, and EZH2 and MAPK1 levels were overexpressed in lumbar nucleus pulposus from human IVDD patients and in LPS-induced NP cells. miR-129-5p overexpression or silencing of MAPK1 promoted proliferation of NP cells, while inhibiting their senescence. EZH2 inhibited miR-129-5p through H3K27me3 modification in the miR-129-5p promoter. miR-129-5p could target the downregulation of MAPK1 expression. EZH2 overexpression increased the release of inflammatory factors and cell senescence factors, which was reversed by miR-129-5p agomir in vivo. CONCLUSIONS: Taken together, EZH2 inhibits miR-129-5p through H3K27me3 modification, which upregulates MAPK1, thereby promoting the development of IVDD.

Metallopolymer Particle Engineering via Etching of Boronate Polymers toward High-Performance Overall Water Splitting Catalysts.

Metallopolymers combine the property features of both metallic compounds and organic polymers, representing a typical direction for the design of high-performance hybrid materials. Here, a highly adaptive etching method to create pores and cavities in the metallopolymer particles is established. Starting from boronate polymer (BP) and inorganic@BP core-shell particles, porous, hollow, and yolk-shell metallopolymer particles can be fabricated, respectively. By taking advantage of the easy control over composition and pore/cavity structure, these metallopolymer particles provide a universal platform for the fabrication of nitrogen, boron co-doped carbon nanocomposites loaded with metals (M-NBCs). The as-prepared M-NBCs exhibit remarkable catalytic activities toward oxygen evolution reaction and hydrogen evolution reaction. An alkaline overall water splitting cell assembled by using M-NBCs as the anode and cathode can be driven by a single AAA battery. The proposed strategy for the construction of metallopolymer composites may enlighten for the design of complex hybrid nanomaterials.

Screening of Minimalist Noncanonical Sites in Duplex DNA and RNA Reveals Context and Motif-Selective Binding by Fluorogenic Base Probes.

We hypothesize that programmable hybridization to noncanonical nucleic acid motifs may be achieved by macromolecular display of binders to individual noncanonical pairs (NCPs). As each recognition element may individually have weak binding to an NCP, we developed a semi-rational approach to detect low affinity interactions between selected nitrogenous bases and noncanonical sites in duplex DNA and RNA. A set of fluorogenic probes was synthesized by coupling abiotic (triazines, pyrimidines) and native RNA bases to thiazole orange (TO) dye. This probe library was screened against duplex nucleic acid substrates bearing single abasic, single NCP, and tandem NCP sites. Probe engagement with NCP sites was reported by 100-1000× fluorescence enhancement over background. Binding is strongly context-dependent, reflective of both molecular recognition and stability: less stable motifs are more likely to bind a synthetic probe. Further, DNA and RNA substrates exhibit entirely different abasic and single NCP binding profiles. While probe binding in the abasic and single NCP screens was monotonous, much richer binding profiles were observed with the screen of tandem NCP sites in RNA, in part due to increased steric accessibility. In addition to known binding interactions between the triazine melamine (M) and T/U sites, the NCP screens identified new targeting elements for pyrimidine-rich motifs in single NCPs and 2×2 internal bulges. We anticipate that semi-rational approaches of this type will lead to programmable noncanonical hybridization strategies at the macromolecular level.

Molecular Exchange of Dynamic Imine Bond for the Etching of Polymer Particles.

The underlying trend of colloidal synthesis has focused on extending the structure and composition complexity of colloidal particles. Hollow and yolk-shell particles are successful examples that have potential applications in frontier fields. In this paper, a facile and controllable etching method based on the molecular exchange of the dynamic imine bond to generate cavities in polymer particles is developed. Starting from boronate ester polymer particles and inorganic@boronate core-shell particles with the imine bonds incorporated in the polymer networks, the etching method easily affords hollow and yolk-shell particles with tunable shell thicknesses. The molecular exchange dynamics analysis indicates that guest amine molecules cause the reconstruction of imine bonds and the leakage of molecular and oligomer fragments, resulting in the formation of the hollow structure. This molecular exchange-based etching method may be of interest in the construction of polymer architectures with increased composition and structure complexities.

Naringin promotes osteogenesis and ameliorates osteoporosis development by targeting JAK2/STAT3 signalling.

Osteoporosis is a systemic bone metabolism disorder, which increases the risk of fractures, and in severe cases it may cause disability or even death. An important factor contributing to osteoporosis is the imbalance between bone formation and resorption. Naringin was reported to promote osteoblast differentiation, thus enhancing bone formation and alleviating osteoporosis development. However, the signalling pathways related to the regulatory mechanism of naringin in osteoporosis development are not clear. Proliferation of bone mesenchymal stem cells (BMSCs) treated with naringin in vitro was detected by CCK-8. An osteogenesis differentiation medium supplemented with naringin was applied to explore the effects of naringin on BMSC osteogenic differentiation, as detected by Alizarin red staining. Ovariectomy (OVX)-induced postmenopausal osteoporosis (PMOP) rats were orally administered with naringin. Dual-energy X-ray absorptiometry (DEXA) and micro-CT were applied to measure bone mineral density (BMD), bone volume/total volume (BV/TV), trabecula thickness (Tb.Th), trabecula number (Tb.N), trabecular separation (Tb.Sp) and bone surface/bone volume (BS/BV). H&E staining was performed to show pathological changes of the femur in PMOP rats after naringin treatment. Bone metabolism indicators were assessed by ELISA. We found that naringin suppressed the activation of the JAK2/STAT3 pathway. Naringin promoted BMSC proliferation and osteogenic differentiation. Furthermore, naringin alleviates bone loss and improves abnormal bone metabolism of PMOP rats. Collectively, naringin promotes BMSC osteogenic differentiation to ameliorate osteoporosis development by targeting JAK2/STAT3 signalling.