TMK-based cell-surface auxin signalling activates cell-wall acidification.

The phytohormone auxin controls many processes in plants, at least in part through its regulation of cell expansion1. The acid growth hypothesis has been proposed to explain auxin-stimulated cell expansion for five decades, but the mechanism that underlies auxin-induced cell-wall acidification is poorly characterized. Auxin induces the phosphorylation and activation of the plasma membrane H+-ATPase that pumps protons into the apoplast2, yet how auxin activates its phosphorylation remains unclear. Here we show that the transmembrane kinase (TMK) auxin-signalling proteins interact with plasma membrane H+-ATPases, inducing their phosphorylation, and thereby promoting cell-wall acidification and hypocotyl cell elongation in Arabidopsis. Auxin induced interactions between TMKs and H+-ATPases in the plasma membrane within seconds, as well as TMK-dependent phosphorylation of the penultimate threonine residue on the H+-ATPases. Our genetic, biochemical and molecular evidence demonstrates that TMKs directly phosphorylate plasma membrane H+-ATPase and are required for auxin-induced H+-ATPase activation, apoplastic acidification and cell expansion. Thus, our findings reveal a crucial connection between auxin and plasma membrane H+-ATPase activation in regulating apoplastic pH changes and cell expansion through TMK-based cell surface auxin signalling.

SPA, a Stigma-style-transmitting tract Physical microenvironment Assay for investigating mechano-signaling in pollen tubes.

Accurate sensing and responding to physical microenvironment are crucial for cell function and survival, but the underlying molecular mechanisms remain elusive. Pollen tube (PT) provides a perfect single-cell model for studying mechanobiology since it's naturally subjected to complex mechanical instructions from the pistil during invasive growth. Recent reports have revealed discrepant PT behaviors between in vivo and flat, two-dimensional in vitro cultures. Here, we established the Stigma-style-transmitting tract (TT) Physical microenvironment Assay (SPA) to recapitulate pressure changes in the pistil. This biomimetic assay has enabled us to swiftly identify highly redundant genes, GEF8/9/11/12/13, as new regulators for maintaining PTs integrity during style-to-TT emergence. In contrast to normal growth on solid medium, SPA successfully phenocopied gef8/9/11/12/13 PT in vivo growth-arrest deficiency. Our results suggest the existence of distinct signaling pathways regulating in vivo and in vitro PT integrity maintenance, underscoring the necessity of faithfully mimicking the physical microenvironment for studying plant cell biology.

Unipolar Solution Flow in Calcium-Organic Frameworks for Seawater-Evaporation-Induced Electricity Generation.

Seawater-flow- and -evaporation-induced electricity generation holds significant promise in advancing next-generation sustainable energy technologies. This method relies on the electrokinetic effect but faces substantial limitations when operating in a highly ion-concentrated environment, for example, natural seawater. We present herein a novel solution using calcium-based metal-organic frameworks (MOFs, C12H6Ca2O19·2H2O) for seawater-evaporation-induced electricity generation. Remarkably, Ca-MOFs show an open-circuit voltage of 0.4 V and a short-circuit current of 14 µA when immersed in seawater under natural conditions. Our experiments and simulations revealed that sodium (Na) ions selectively transport within sub-nanochannels of these synthetic superhydrophilic MOFs. This selective ion transport engenders a unipolar solution flow, which drives the electricity generation behavior in seawater. This work not only showcases an effective Ca-MOF for electricity generation through seawater flow/evaporation but also contributes significantly to our understanding of water-driven energy harvesting technologies and their potential applications beyond this specific context.

Investigation of the biocontrol mechanism of a novel Pseudomonas species against phytopathogenic Fusarium graminearum revealed by multi-omics integration analysis.

Phytopathogenic Fusarium graminearum poses significant threats to crop health and soil quality. Although our laboratory-cultivated Pseudomonas sp. P13 exhibited potential biocontrol capacities, its effectiveness against F. graminearum and underlying antifungal mechanisms are still unclear. In light of this, our study investigated a significant inhibitory effect of P13 on F. graminearum T1, both in vitro and in a soil environment. Conducting genomic, metabolomic, and transcriptomic analyses of P13, we sought to identify evidence supporting its antagonistic effects on T1. The results revealed the potential of P13, a novel Pseudomonas species, to produce active antifungal components, including phenazine-1-carboxylate (PCA), hydrogen cyanide (HCN), and siderophores [pyoverdine (Pvd) and histicorrugatin (Hcs)], as well as the dynamic adaptive changes in the metabolic pathways of P13 related to these active ingredients. During the logarithmic growth stage, T1-exposed P13 strategically upregulated PCA and HCN biosynthesis, along with transient inhibition of the tricarboxylic acid (TCA) cycle. However, with growth stabilization, upregulation of PCA and HCN synthesis ceased, whereas the TCA cycle was enhanced, increasing siderophores secretion (Pvd and Hcs), suggesting that this mechanism might have caused continuous inhibition of T1. These findings improved our comprehension of the biocontrol mechanisms of P13 and provided the foundation for potential application of Pseudomonas strains in the biocontrol of phytopathogenic F. graminearum. IMPORTANCE: Pseudomonas spp. produces various antifungal substances, making it an effective natural biocontrol agent against pathogenic fungi. However, the inhibitory effects and the associated antagonistic mechanisms of Pseudomonas spp. against Fusarium spp. are unclear. Multi-omics integration analyses of the in vitro antifungal effects of novel Pseudomonas species, P13, against F. graminearum T1 revealed the ability of P13 to produce antifungal components (PCA, HCN, Pvd, and Hcs), strategically upregulate PCA and HCN biosynthesis during logarithmic growth phase, and enhance the TCA cycle during stationary growth phase. These findings improved our understanding of the biocontrol mechanisms of P13 and its potential application against pathogenic fungi.

Sources and control of impurity during one-pot enzymatic production of dehydroepiandrosterone.

Dehydroepiandrosterone (DHEA) has a promising market due to its capacity to regulate human hormone levels as well as preventing and treating various diseases. We have established a chemical esterification coupled biocatalytic-based scheme by lipase-catalyzed 4-androstene-3,17-dione (4-AD) hydrolysis to obtain the intermediate product 5-androstene-3,17-dione (5-AD), which was then asymmetrically reduced by a ketoreductase from Sphingomonas wittichii (SwiKR). Co-enzyme required for KR is regenerated by a glucose dehydrogenase (GDH) from Bacillus subtilis. This scheme is more environmentally friendly and more efficient than the current DHEA synthesis pathway. However, a significant amount of 4-AD as by-product was detected during the catalytic process. Focused on the control of by-products, we investigated the source of 4-AD and identified that it is mainly derived from the isomerization activity of SwiKR and GDH. Increasing the proportion of glucose in the catalytic system as well as optimizing the catalytic conditions drastically reduced 4-AD from 24.7 to 6.5% of total substrate amount, and the final yield of DHEA achieved 40.1 g/L. Furthermore, this is the first time that both SwiKR and GDH have been proved to be promiscuous enzymes with dehydrogenase and ketosteroid isomerase (KSI) activities, expanding knowledge of the substrate diversity of the short-chain dehydrogenase family enzymes. KEY POINTS: • A strategy of coupling lipase, ketoreductase, and glucose dehydrogenase in producing DHEA from 4-AD • Both SwiKR and GDH are identified with ketosteroid isomerase activity. • Development of catalytic strategy to control by-product and achieve highly selective DHEA production.

Antioxidant Properties of Platycladus orientalis Flavonoids for Treating UV-Induced Damage in Androgenetic Alopecia Hair.

BACKGROUND: Androgenetic alopecia (AGA) causes thinning hair, but poor hair quality in balding areas and damage from UV radiation have been overlooked. Plant extracts like Platycladus orientalis flavonoids (POFs) may improve hair quality in AGA. This study examines POFs' effectiveness in treating AGA-affected hair and repairing UV-induced damage. METHODS: Hair samples were analyzed using scanning electron microscopy (SEM) to examine surface characteristics, electron paramagnetic resonance (EPR) spectroscopy to measure free radicals in the hair, and spectrophotometry to assess changes in hair properties. RESULTS: POFs effectively removed hydroxyl radicals from keratinocytes and had antioxidant properties. They also reduced UV-induced damage to AGA hair by mitigating the production of melanin free radicals. Following POF treatment, the reduction in peroxidized lipid loss in AGA hair was notable at 59.72%, thereby effectively delaying the progression of hair color change. Moreover, protein loss decreased by 191.1 µ/g and tryptophan loss by 15.03%, ultimately enhancing hair's tensile strength. CONCLUSION: compared to healthy hair, hair damaged by AGA shows more pronounced signs of damage when exposed to UV radiation. POFs help protect balding hair by reducing oxidative damage and slowing down melanin degradation.

ß-Nicotinamide Mononucleotide Promotes Cell Proliferation and Hair Growth by Reducing Oxidative Stress.

ß-Nicotinamide mononucleotide (NMN) has shown promising effects on intestinal health, and it is extensively applied as an anti-aging and Alzheimer's disease therapeutic, due to its medicinal properties. The effects of NMN on the growth of mouse hair were observed after hair removal. The results indicated that NMN can reverse the state of hair follicle atrophy, hair thinning, and hair sparsity induced by dihydrotestosterone (DHT), compared to that of minoxidil. In addition, the action mechanisms of NMN promoting hair growth in cultured human dermal papilla cells (HDPCs) treated with DHT were investigated in detail. The incubation of HDPCs with DHT led to a decrease in cell viability and the release of inflammatory mediators, including interleukin-6 (IL-6), interleukin-1Beta (IL-1ß) and tumor necrosis factor Alpha (TNF-α). It was found that NMN can significantly lower the release of inflammatory factors induced by DHT in HDPCs. HDPCs cells are protected from oxidative stress damage by NMN, which inhibits the NF-κB p65 inflammatory signaling pathway. Moreover, the levels of androgen receptor (AR), dickkopf-1 (DKK-1), and ß-catenin in the HDPCs were assessed using PCR, indicating that NMN can significantly enhance the expression of VEGF, reduced IL-6 levels and suppress the expression of AR and DKK-1, and notably increase ß-catenin expression in DHT-induced HDPCs.

The Factor beyond Schmidt's Criteria Impacting the Photo-Induced [2+2] Cycloaddition Reactivity and Photoactuation of Molecular Crystals Based on Cyclic Chalcone Analogues.

Generally, the potential reactive "olefin pairs" in the molecular crystals satisfying Schmidt's criteria could undergo topological [2+2] cycloaddition. In this study, another factor that affects the photodimerization reactivity of chalcone analogues was found. The cyclic chalcone analogues of (E)-2-(2,4-dichlorobenzylidene)-2,3-dihydro-1H-inden-1-one (BIO), (E)-2-(naphthalen-2-ylmethylene)-2,3-dihydro-1H-inden-1-one (NIO), (Z)-2-(2,4-dichlorobenzylidene)benzofuran-3(2H)-one (BFO), and (Z)-2-(2,4-dichlorobenzylidene)benzo[b]thiophen-3(2H)-one (BTO) have been synthesized. While the geometrical parameters for the molecular packing of the above four compounds did not exceed Schmidt's criteria, [2+2] cycloaddition did not occur in the crystals of BIO and BTO. The single crystal structures and Hirshfeld surface analyses revealed that interactions of C=O⋅⋅⋅H (CH2 ) existed between adjacent molecules in the crystal of BIO. Therefore, the carbonyl and methylene groups linked with one carbon atom in carbon-carbon double bond were tightly confined in the lattice, acting as a tweezer to inhibit free movement of the double bond and suppressing [2+2] cycloaddition. In the crystal of BTO, similar interactions of Cl⋅⋅⋅S and C=O⋅⋅⋅H (C6 H4 ) prevented free movement of the double bond. In contrast, the intermolecular interaction of C=O⋅⋅⋅H only exists around the carbonyl group in the crystals of BFO and NIO, leaving the C=C double bonds to move freely and allowing the occurrence of [2+2] cycloaddition. Driven by photodimerization, the needle-like crystals of BFO and NIO displayed evident photo-induced bending behavior. This work demonstrates that the intermolecular interactions around carbon-carbon double bond affect the [2+2] cycloaddition reactivity except for Schmidt's criteria. These findings provide valuable insights into the design of photomechanical molecular crystalline materials.

Induced Resistance Mechanism of Bacillus velezensis S3-1 Against Pepper Wilt.

In recent years, pepper wilt has emerged as a pivotal constraint on pepper yield augmentation. Bacillus velezensis S3-1, with a wide array of hosts, can be used as both a biocontrol agent and biofertilizer. Nonetheless, the precise mechanisms underpinning its employment in combating pepper wilt remain cloaked in ambiguity. In our study, we found that B. velezensis S3-1 could significantly inhibit Fusarium sp. F1T that caused pepper wilt. S3-1 could effectively inhibit both the growth and germination of F1T conidia, leading to a reduction in the spore germination percentage from 83.2 to 37.1% in vitro experiments. Additionally, leaf detachment experiments revealed that the volatile compounds produced by S3-1 could inhibit the spread of pepper leaf spot area. Moreover, we observed a significant decrease in the content of malondialdehyde (MDA) in pepper treated with S3-1, along with a significant increase in the content of soluble protein, polyphenol oxidase (PPO), peroxidase (POD), and phenylalanine ammonia-lyase (PAL) in pepper. Furthermore, RT-PCR analysis showed that the expression of the defense genes CaPR 1 and CaPIN II in pepper after treatment with S3-1 was significantly upregulated, suggesting that S3-1 had the potential to induce systemic resistance in pepper, thereby enhancing its disease resistance. Hence, our findings suggest that S3-1 can be a promising biocontrol agent for managing pepper wilt in modern agriculture.

Real-Time Image-Guided Navigation in the Management of Alveolar Cleft Repair.

Objectives: To present the use of dynamic navigation system in the repair of alveolar cleft. Patients and Participants: A total of three non-syndromic patients with unilateral alveolar cleft were involved in this study. Real-time computer-aided navigation were used to achieve restoration and reconstruction with standardized surgical technique. Methods: With the individual virtual 3-dimensional (3-D) modeling based on computed tomography (CT) data, preoperative planning and surgical simulation were carried out with the navigation system. During preoperative virtual planning, the defect volume or the quantity of graft is directly assessed at the surgical region. With the use of this system, the gingival periosteum flap incision can be tracked in real-time, and the bone graft can be navigated under the guidance of the 3-D views until it matches the preoperatively planned position. Results: Three patients with alveolar cleft were successfully performed under navigation guidance. Through the model alignment procedure, accurate matches between the actual intraoperative position and the CT images were achieved within the systematic error of 0.3 mm. The grafted bone was implanted according to the preoperative plan with the aid of instrument- and probe-based navigation. All the patients were healed well without serious complications. Conclusions: These findings suggest that image-guided surgical navigation, including preoperative planning, surgical simulation, postoperative assessment, and computer-assisted navigation was feasible and yielded good clinical outcomes. Clinical relevance: This dynamic navigation could be proved to be a valuable option for this complicated surgical procedure in the management of alveolar cleft repair.

Invertible plasmonic spin-Hall effect at nanoscale based on U-shaped optical slot nanoantenna.

A U-shaped optical slot nanoantenna with a footprint size of 300 nm by 300 nm is proposed to achieve invertible plasmonic spin-Hall effect at nanoscale. The interference between the SPPs excited by the different plasmon resonances in the antenna enables the nanostucture to break the spin degeneracy. Besides, the SPP orbitals for the two spins are invertible while changing the incident wavelength, which is attributed to the dispersive phase shift between the different plasmon resonances in the antenna. The SPP intensity extinction ratio can be improved by employing a U-shaped slot antenna array. The strong spin-orbit coupling property together with the ultra-compact size and invertible spin-controlled SPP orbitals enable the structure promising applications in spin-optoelectronics and plasmonics.

lncRNA-AC130710 targeting by miR-129-5p is upregulated in gastric cancer and associates with poor prognosis.

Long noncoding RNAs (lncRNAs) play an important role in cancer occurrence and development. However, there is largely unknown about lncRNAs significance in the diagnosis and treatment of gastric cancer. In our study, we focused on AC130710, one of lncRNAs. Gastric cancer tissues and adjacent tissues were gathered from 78 patients with gastric cancer. The AC130710 levels were detected by reverse transcription polymerase chain reaction (RT-PCR). Then, we further analyzed the association between AC130710 level and the clinicopathological factors of patients with gastric cancer. Finally, the molecular mechanism underling AC130710 highly expressed in gastric cancer cells was explored. The results showed that AC130710 in cancer tissues from patients with gastric cancer was significantly higher than those in adjacent noncancerous tissues (P < 0.05). Its expression level was significantly associated with tumor size (P = 0.013), tumor-node-metastasis (TNM) stages (P = 0.030), and distal metastasis (P = 0.018). AC130710 expression in MGC-803 was significantly higher than that in normal gastric mucosa cell line GES-1 (P < 0.001). Moreover, miR-129-5p may play an important role in the downregulation of AC130710 in gastric cancer cells. These results indicated that lncRNA-AC130710 may be a potential tumor marker for gastric cancer prognosis.

Plasmon-Switched Kinetics for Formic Acid Dehydrogenation: Selective Adsorption Driven by Local Field and Hot Carriers.

Understanding illumination-mediated kinetics is essential for catalyst design in plasmon catalysis. Here we prepare Pd-based plasmonic catalysts with tunable electronic structures to reveal the underlying illumination-enhanced kinetic mechanisms for formic acid (HCOOH) dehydrogenation. We demonstrate a kinetic switch from a competitive Langmuir-Hinshelwood adsorption mode in dark to a non-competitive type under irradiation triggered by local field and hot carriers. Specifically, the electromagnetic field induces a spatial-temporal separation of dehydrogenation-favorable configurations of reactant molecule HCOOH and HCOO- due to their natural different polarities. Meanwhile, the generated energetic carriers can serve as active sites for selective molecular adsorption. The hot electrons act as adsorption sites for HCOOH, while holes prefer to adsorb HCOO-. Such unique non-competitive adsorption kinetics induced by plasmon effects serves as another typical characteristic of plasmonic catalysis that remarkably differs from thermocatalysis. This work unravels unique adsorption transformations and a kinetic switching driven by plasmon nonthermal effects.

Fe3O4/biochar modified with molecularly imprinted polymer as efficient persulfate activator for salicylic acid removal from wastewater: Performance and specific recognition mechanism.

In this study, a novel Fe3O4-based biochar coupled surface-imprinted polymer was constructed via simple hydrothermal route for salicylic acid recognition and degradation in advanced oxidation processes. The material exhibited excellent adsorption capability, up to 118.23 mg g-1, and efficient degradation performance, 87.44% removal rate within 240 min, based on integrating the advantages of both huge specific surface area as well as abundant functional groups from biochars and specific recognition sites from imprinted cavities. Moreover, high selectivity coefficient (11.67) showed stable recognition in single and binary systems. SO4•- and •OH were confirmed as reactive oxygen species in catalytic reaction according to quenching experiments and EPR analysis. The degradation mechanism and pathway were unraveled by DFT calculations and LC-MS. Furthermore, the results of toxicity evaluation, stability and reusability demonstrated application potential in the field of water environment restoration. This study confirmed that molecular imprinting provided a promising solution to targeted removal of emerging environmental pollutants by degrading after the enrichment of pollutants to the composites surface.

Modulation of copper sites in porphyrin metal-organic frameworks for electrochemical ascorbic acid sensing.

Two metal-organic frameworks (MOFs) with different Cu-centered coordination structures were synthesized. By introducing 4,4-bipyridine as a linker in the Cu-MOFs, we have discovered that Cu-O, instead of Cu-N, is the active site with higher electrocatalytical activity towards ascorbic acid, which is essential to understand and develop Cu-based ascorbic acid sensors.

An interference coating of metamaterial as an ultrathin light absorber in the violet-to-infrared regime.

A metamaterial with brief and ultrathin structure performs high efficiency in light absorption. An upright aluminum nanorod array (Al NRA) is obliquely deposited, measured, and analyzed its optical property. The Al NRA performs high efficiency of light absorption and low reflectance simultaneously. Based on the measured refractive index and impedances, the wave propagation through the Al NRA is traced to demonstrate the destructive interference that leads to antireflection. According to the analysis of wave tracing, an Al semicontinuous film with thickness of 15nm is introduced under an Al NRA with thickness of only 245nm as a brief and thin two-layered structure. The broadband and polarization-independent light absorption is measured over the violet-to-infrared regime.

Comprehensive Analysis of Ubiquitously Expressed Genes in Humans from A Data-driven Perspective.

Comprehensive characterization of spatial and temporal gene expression patterns in humans is critical for uncovering the regulatory codes of the human genome and understanding the molecular mechanisms of human diseases. Ubiquitously expressed genes (UEGs) refer to the genes expressed across a majority of, if not all, phenotypic and physiological conditions of an organism. It is known that many human genes are broadly expressed across tissues. However, most previous UEG studies have only focused on providing a list of UEGs without capturing their global expression patterns, thus limiting the potential use of UEG information. In this study, we proposed a novel data-driven framework to leverage the extensive collection of ∼ 40,000 human transcriptomes to derive a list of UEGs and their corresponding global expression patterns, which offers a valuable resource to further characterize human transcriptome. Our results suggest that about half (12,234; 49.01%) of the human genes are expressed in at least 80% of human transcriptomes, and the median size of the human transcriptome is 16,342 genes (65.44%). Through gene clustering, we identified a set of UEGs, named LoVarUEGs, which have stable expression across human transcriptomes and can be used as internal reference genes for expression measurement. To further demonstrate the usefulness of this resource, we evaluated the global expression patterns for 16 previously predicted disallowed genes in islet beta cells and found that seven of these genes showed relatively more varied expression patterns, suggesting that the repression of these genes may not be unique to islet beta cells.

Photo-enhanced dehydrogenation of formic acid on Pd-based hybrid plasmonic nanostructures.

Coupling visible light with Pd-based hybrid plasmonic nanostructures has effectively enhanced formic acid (FA) dehydrogenation at room temperature. Unlike conventional heating to achieve higher product yield, the plasmonic effect supplies a unique surface environment through the local electromagnetic field and hot charge carriers, avoiding unfavorable energy consumption and attenuated selectivity. In this minireview, we summarized the latest advances in plasmon-enhanced FA dehydrogenation, including geometry/size-dependent dehydrogenation activities, and further catalytic enhancement by coupling local surface plasmon resonance (LSPR) with Fermi level engineering or alloying effect. Furthermore, some representative cases were taken to interpret the mechanisms of hot charge carriers and the local electromagnetic field on molecular adsorption/activation. Finally, a summary of current limitations and future directions was outlined from the perspectives of mechanism and materials design for the field of plasmon-enhanced FA decomposition.

Synergistic Combination of Fermi Level Equilibrium and Plasmonic Effect for Formic Acid Dehydrogenation.

Developing an efficient catalyst for formic acid (FA) dehydrogenation is a promising strategy for safe hydrogen storage and transportation. Herein, we successfully developed trimetallic NiAuPd heterogeneous catalysts through a galvanic replacement reaction and a subsequent chemical reduction process to boost hydrogen generation from FA decomposition at room temperature by coupling Fermi level engineering with plasmonic effect. We demonstrated that Ni worked as an electron reservoir to donate electrons to Au and Pd driven by Fermi level equilibrium whereas plasmonic Au served as an optical absorber to generate energetic hot electrons and a charge-redistribution mediator. Ni and Au worked cooperatively to promote the charge heterogeneity of surface-active Pd sites, leading to enhanced chemisorption of formate-related intermediates and eventually outstanding activity (342 mmol g-1 h-1 ) compared with bimetallic counterpart. This work offers excellent insight into the rational design of efficient catalysts for practical hydrogen energy exploitation.

Leukemia Inhibitory Factor Facilitates Self-Renewal and Differentiation and Attenuates Oxidative Stress of BMSCs by Activating PI3K/AKT Signaling.

Objective: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) remains a hopeful therapeutic approach for bone defect reconstruction. Herein, we investigated the effects and mechanisms of leukemia inhibitory factor (LIF) in the function and viability of hypoxic BMSCs as well as bone defect repair. Methods: The effects of LIF on apoptosis (flow cytometry, TUNEL staining), mitochondrial activity (JC-1 staining), proliferation (colony formation, EdU staining), and differentiation (CD105, CD90, and CD29 via flow sorting) were examined in hypoxic BMSCs. LIF, LIFR, gp130, Keap1, Nrf2, antioxidant enzymes (SOD1, catalase, GPx-3), bone-specific matrix proteins (ALP, BSP, OCN), PI3K, and Akt were detected via immunoblotting or immunofluorescent staining. BMSCs combined with biphasic calcium phosphate scaffolds were implanted into calvarial bone defect mice, and the therapeutic effect of LIF on bone defect was investigated. Results: Hypoxic BMSCs had increased apoptosis and oxidative stress and reduced mitochondrial activity. Additionally, LIF, LIFR, and gp130 were upregulated and PI3K/Akt activity was depressed in hypoxic BMSCs. Upregulated LIF alleviated apoptosis and oxidative stress and heightened mitochondrial activity and PI3K/Akt signaling in hypoxic BMSCs. Additionally, LIF overexpression promoted self-renewal and osteogenic differentiation of BMSCs with hypoxic condition. Mechanically, LIF facilitated self-renewal and differentiation as well as attenuated oxidative stress of BMSCs through enhancing PI3K/AKT signaling activity. Implantation of LIF-overexpressed BMSC-loaded BCP scaffolds promoted osteogenesis as well as alleviated oxidative stress and apoptosis through PI3K/Akt signaling. Conclusion: Our findings demonstrate that LIF facilitates self-renewal and differentiation and attenuates oxidative stress of BMSCs by PI3K/AKT signaling.