Design, synthesis, and biological evaluation of novel sesquiterpene lactone derivatives as PKM2 activators with potent anti-ulcerative colitis activities.

Pyruvate kinase isoform 2 (PKM2) is closely related to the regulation of Th17/Treg balance, which is considered to be an effective strategy for UC therapy. Parthenolide (PTL), a natural product, only possesses moderate PKM2-activating activity. Thus, five series of PTL derivatives are designed and synthesized to improve PKM2-activated activities and anti-UC abilities. Through detailed structure optimization, B4 demonstrates potent T-cell anti-proliferation activity (IC50 = 0.43 µM) and excellent PKM2-activated ability (AC50 = 0.144 µM). Subsequently, through mass spectrometry analysis, B4 is identified to interact with Cys423 of PKM2 via covalent-bond. Molecular docking and molecular dynamic simulation results reveal that the trifluoromethoxy of B4 forms a stronger hydrophobic interaction with Ala401, Pro402, and Ile403. In addition, B4 has a significant effect only on Th17 cell differentiation, thereby regulating the Th17/Treg balance. The effect of B4 on Th17/Treg imbalance can be attributed to inhibition of PKM2 dimer translocation and suppression of glucose metabolism. Finally, B4 can notably ameliorate the symptoms of dextran sulfate sodium (DSS)-induced colitis in mouse model in vivo. Thus, B4 is confirmed as a potent PKM2 activator, and has the potential to develop as a novel anti-UC agent.

Impact of anesthesia-related genes on prognosis and tumor microenvironment in hepatocellular carcinoma: A comprehensive analysis.

Hepatocellular carcinoma (HCC), renowned for its bleak prognosis and high recurrence rates, necessitates innovative strategies for prognosis assessment and therapeutic intervention. In this pursuit, we systematically investigated the influence of anesthesia-related genes (ANARGs) on HCC outcomes. Leveraging data from The Cancer Genome Atlas (TCGA), our study scrutinized RNA sequencing data and clinical profiles from 374 HCC patients alongside 50 non-tumor liver samples to unravel ANARG expression patterns and their clinical relevance. Employing consensus clustering, we segregated HCC samples into two distinct subtypes based on ANARG profiles, unveiling significant survival disparities between them. Further differential expression analysis pinpointed pivotal genes and pathways distinguishing these subtypes, notably implicating lipid metabolism and the MTOR signaling pathway in HCC pathogenesis. A prognostic model, comprising five key ANARGs (DAGLA, CYP26B, HAVCR, G6PD and AKR1B), exhibited robust predictive capability for patient outcomes, validated across independent patient cohorts. Furthermore, immune infiltration analysis uncovered a nuanced interplay between ANARG expression and the tumor immune microenvironment, spotlighting variations in immune cell infiltration and function across the identified HCC subtypes. This comprehensive analysis underscores not only the prognostic significance of ANARGs in HCC but also their potential to modulate the tumor microenvironment, providing novel insights for tailoring anesthetic management and therapeutic strategies in HCC care. Our findings advocate for a more integrative approach to HCC management, amalgamating molecular profiling with traditional clinical parameters to refine patient stratification and personalize treatment strategies.

Discovery of a Novel CSF-1R Inhibitor with Highly Improved Pharmacokinetic Profiles and Superior Efficacy in Colorectal Cancer Immunotherapy.

Blocking CSF-1/CSF-1R pathway has emerged as a promising strategy to remodel tumor immune microenvironment (TME) by reprogramming tumor-associated macrophages (TAMs). In this work, a novel CSF-1R inhibitor C19 with a highly improved pharmacokinetic profile and in vivo anticolorectal cancer (CRC) efficiency was successfully discovered. C19 could effectively reprogram M2-like TAMs to M1 phenotype and reshape the TME by inducing the recruitment of CD8+ T cells into tumors and reducing the infiltration of immunosuppressive Tregs/MDSCs. Deeper mechanistic studies revealed that C19 facilitated the infiltration of CD8+ T cells by enhancing the secretion of chemokine CXCL9, thus significantly potentiating the anti-CRC efficiency of PD-1 blockade. More importantly, C19 combined with PD-1 mAb could induce durable antitumor immune memory, effectively overcoming the recurrence of CRC. Taken together, our findings suggest that C19 is a promising therapeutic option for sensitizing CRC to anti-PD-1 therapy.

Comparison of Thoracoscopy-Guided Thoracic Paravertebral Block and Ultrasound-Guided Thoracic Paravertebral Block in Postoperative Analgesia of Thoracoscopic Lung Cancer Radical Surgery: A Randomized Controlled Trial.

INTRODUCTION: Ultrasound-guided thoracic paravertebral block (UTPB) is widely used for postoperative analgesia in thoracic surgery. However, it has many disadvantages. Thoracoscopy-guided thoracic paravertebral block (TTPB) is a new technique for thoracic paravertebral block (TPB). In this study, we compared the use of TTPB and UTPB for pain management after thoracoscopic radical surgery for lung cancer. METHODS: In total, 80 patients were randomly divided 1:1 into the UTPB group and the TTPB group. The surgical time of TPB, the success rate of the first puncture, block segment range, visual analog scale (VAS) scores at 2, 6, 12, 24, and 48 h post operation, and the incidence of postoperative adverse reactions were compared between the two groups. RESULTS: The surgical time of TPB was significantly shorter in the TTPB group than in the UTPB group (2.2 ± 0.3 vs. 5.7 ± 1.7 min, t = - 12.411, P < 0.001). The success rate of the first puncture and the sensory block segment were significantly higher in the TTPB group than in the UTPB group (100% vs. 76.9%, χ2 = 8.309, P < 0.001; 6.5 ± 1.2 vs. 5.1 ± 1.3 levels, t = - 5.306, P < 0.001, respectively). The VAS scores were significantly higher during rest and coughing at 48 h post operation than at 2, 6, 12, and 24 h post operation in the TTPB group. The VAS scores were significantly lower during rest and coughing at 12 and 24 h post operation in the TTPB group than in the UTPB group (rest: 2.5 ± 0.4 vs. 3.4 ± 0.6, t = 7.325, P < 0.001; 2.5 ± 0.5 vs. 3.5 ± 0.6, t = 7.885, P < 0.001; coughing: 3.4 ± 0.6 vs. 4.2 ± 0.7, t = 5.057, P < 0.001; 3.4 ± 0.6 vs. 4.2 ± 0.8, t = 4.625, P < 0.001, respectively). No significant difference was observed in terms of postoperative adverse reactions between the two groups. CONCLUSIONS: Compared with UTPB, TTPB shows advantages, such as simpler and more convenient surgery, shorter surgical time, a higher success rate of the first puncture, wider block segments, and superior analgesic effect. TTPB can effectively reduce postoperative pain due to thoracoscopic lung cancer radical surgery. TRIAL REGISTRATION: https://www.chictr.org.cn , identifier ChiCTR2300072005, prospectively registered on 31/05/2023.

Discovery of a Novel Orally Bioavailable FLT3-PROTAC Degrader for Efficient Treatment of Acute Myeloid Leukemia and Overcoming Resistance of FLT3 Inhibitors.

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis-targeting chimeras (PROTACs) represent a promising approach to eliminate the resistance of FLT3 inhibitors. However, due to the poor druggability of PROTACs, the development of orally bioavailable FLT3-PROTACs faces great challenges. Herein, a novel orally bioavailable FLT3-ITD degrader A20 with excellent pharmacokinetic properties was discovered through reasonable design. A20 selectively inhibited the proliferation of FLT3-ITD mutant acute myeloid leukemia (AML) cells and potently induced FLT3-ITD degradation through the ubiquitin-proteasome system. Notably, oral administration of A20 resulted in complete tumor regression on subcutaneous AML xenograft models. Furthermore, on systemic AML xenograft models, A20 could completely eliminate the CD45+CD33+ human leukemic cells in murine and significantly prolonged the survival time of mice. Most importantly, A20 exerted significantly improved antiproliferative activity against drug-resistant AML cells compared to existing FLT3 inhibitors. These findings suggested that A20 could serve as a promising drug candidate for relapsed or refractory AML.

Discovery and preclinical evaluations of TQB3616, a novel CDK4-biased inhibitor.

Among small-molecule CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) approved for metastatic breast cancers, abemaciclib has a more tolerable adverse effects in clinic. This is attributable to preferential inhibition of CDK4 over CDK6. In our search for a biased CDK4 inhibitor, we discovered a series of pyrimidine-indazole inhibitors. SAR studies led us to TQB3616 as a preferential CDK4 inhibitor. TQB3616 exhibited improvements in both enzymatic and cellular proliferation inhibitory potency when tested side-by-side with the FDA approved palbociclib and abemaciclib. TQB3616 also possessed favorable PK profile in multiple species. These differentiated properties, together with excellent GLP safety profile warranted TQB3616 moving to clinic. TQB3616 entered into clinical development in 2019 and currently in phase III clinical trials (NCT05375461, NCT05365178).

CSF1R inhibition reprograms tumor-associated macrophages to potentiate anti-PD-1 therapy efficacy against colorectal cancer.

PD-1 blockade therapy has made great breakthroughs in treatment of multiple solid tumors. However, patients with microsatellite-stable (MSS) colorectal cancer (CRC) respond poorly to anti-PD-1 immunotherapy. Although CRC patients with microstatellite instability (MSI) or microsatellite instability-high (MSI-H) can benefit from PD-1 blockade therapy, there are still some problems such as tumor recurrence. Tumor-associated macrophages (TAMs), most abundant immune components in tumor microenvironment (TME), largely limit the therapeutic efficacy of anti-PD-1 against CRC. The CSF1/CSF1R pathway plays a key role in regulating macrophage polarization, and blocking CSF1R signaling transduction may be a potential strategy to effectively reprogram macrophages and remodel TME. Here, we found that increasing expression of CSF1R in macrophages predicted poor prognosis in CRC cohort. Furthermore, we discovered a novel potent CSF1R inhibitor, PXB17, which significantly reprogramed M2 macrophages to M1 phenotype. Mechanically, PXB17 significantly blocked activation of PI3K/AKT/mTORC1 signaling, resulting in inhibition of cholesterol biosynthesis. Results from 3D co-culture system suggested that PXB17-repolarized macrophages could induce infiltration of CD8+ T lymphocytes in tumors and improve the immunosuppressive microenvironment. In vivo, PXB17 significantly halted CRC growth, with a stronger effect than PLX3397. In particular, PXB17 potently enhanced therapeutic activity of PD-1 mAb in CT-26 (MSS) model and prevented tumor recurrence in MC-38 (MSI-H) model by promoting formation of long-term memory immunity. Our study opens a new avenue for CSF1R in tumor innate and adaptive anti-tumor immunomodulatory activity and suggests that PXB17 is a promising immunotherapy molecule for enhancing the efficacy of PD-1 mAb or reducing tumor recurrence of CRC.

Predictions of photophysical properties of phosphorescent platinum(II) complexes based on ensemble machine learning approach.

Cyclometalated Pt(II) complexes are popular phosphorescent emitters with color-tunable emissions. To render their practical applications as organic light-emitting diodes emitters, it is required to develop Pt(II) complexes with high radiative decay rate constant and photoluminescence (PL) quantum yield. Here, a general protocol is developed for accurate predictions of emission wavelength, radiative decay rate constant, and PL quantum yield based on the combination of first-principles quantum mechanical method, machine learning, and experimental calibration. A new dataset concerning phosphorescent Pt(II) emitters is constructed, with more than 200 samples collected from the literature. Features containing pertinent electronic properties of the complexes are chosen and ensemble learning models combined with stacking-based approaches exhibit the best performance, where the values of squared correlation coefficients are 0.96, 0.81, and 0.67 for the predictions of emission wavelength, PL quantum yield and radiative decay rate constant, respectively. The accuracy of the protocol is further confirmed using 24 recently reported Pt(II) complexes, which demonstrates its reliability for a broad palette of Pt(II) emitters.

Tung oil-based waterborne UV-curable coatings via cellulose nanofibril stabilized Pickering emulsions for self-healing and anticorrosion application.

In this study, waterborne UV-curable coatings with self-healing properties based on transesterification were prepared using renewable biomass resources for anti-corrosion application. Tung oil (TO)-based oligomer (TMHT) was synthesized through Diels-Alder reaction of TO with maleic anhydride, subsequent ring opening reaction with hydroxyethyl acrylate (HEA), and final neutralize reaction with triethylamine. A series of waterborne UV-curable coatings were prepared from cellulose nanofibrils (CNF) stabilized TMHT-based Pickering emulsions after drying and UV light-curing processes. It is suggested that CNF significantly improved the storage stability of Pickering emulsions. The obtained waterborne UV-curable coatings with CNF of 1-3 wt% exhibited remarking coating and mechanical performance (pencil hardness up to 5 H, adhesion up to 2 grade, flexibility of 2 mm, tensile strength up to 11.6 MPa, etc.), great transmittance (82.3 %-80.8 %) and great corrosion resistance (|Z|0.01Hz up to 5.4 × 106 Ω·cm2). Because of the presence of the dynamic ester bonds in TMHT, the coatings exhibited excellent self-healing performance (78.05 %-56.34 %) at 150 °C without catalyst and external force. More importantly, the |Z|0.01Hz of the self-healing coating was higher than that of the scratched coating, indicating that the self-healing performance could extend the service life of the coating in corrosion resistant application.

A new wave of innovations within the DNA damage response.

Genome instability has been identified as one of the enabling hallmarks in cancer. DNA damage response (DDR) network is responsible for maintenance of genome integrity in cells. As cancer cells frequently carry DDR gene deficiencies or suffer from replicative stress, targeting DDR processes could induce excessive DNA damages (or unrepaired DNA) that eventually lead to cell death. Poly (ADP-ribose) polymerase (PARP) inhibitors have brought impressive benefit to patients with breast cancer gene (BRCA) mutation or homologous recombination deficiency (HRD), which proves the concept of synthetic lethality in cancer treatment. Moreover, the other two scenarios of DDR inhibitor application, replication stress and combination with chemo- or radio- therapy, are under active clinical exploration. In this review, we revisited the progress of DDR targeting therapy beyond the launched first-generation PARP inhibitors. Next generation PARP1 selective inhibitors, which could maintain the efficacy while mitigating side effects, may diversify the application scenarios of PARP inhibitor in clinic. Albeit with unavoidable on-mechanism toxicities, several small molecules targeting DNA damage checkpoints (gatekeepers) have shown great promise in preliminary clinical results, which may warrant further evaluations. In addition, inhibitors for other DNA repair pathways (caretakers) are also under active preclinical or clinical development. With these progresses and efforts, we envision that a new wave of innovations within DDR has come of age.

Exploring il-6 as a marker of respiratory health in athletes: insights from psittacosis pneumonia research

Objective: This study aims to explore the correlation between interleukin-6 (IL-6) levels and the condition of patients with psittacosis pneumonia, and extend these insights to the context of respiratory health in athletes.Methods: In a retrospective analysis, we included 14 patients diagnosed with psittacosis pneumonia (parrot fever) treated in our hospital from April 2018 to September 2021 as the study group (SG). As a control group (CG), we selected 20 patients with common pneumonia treated during the same period. We compared IL-6 levels between these groups and recorded changes in IL-6 levels in the SG before and after treatment. Additionally, we analyzed the correlation of IL-6 levels with procalcitonin (PCT) and C-reactive protein (CRP) levels.Results:The IL-2 levels in the SG were significantly lower than those in the CG, while IL-6 levels were significantly higher. No significant difference was observed in IL-10 and IL-6 levels between the groups (P>0.05). The average IL-6 level in the SG was 80.78±46.20 ng/L before treatment and 7.86±6.73 ng/L after treatment, showing a significant reduction (P<0.05). There was a significant positive correlation between IL-6 levels and PCT levels in the SG (r=0.2659, P<0.05), but the correlation with CRP levels was not significant (r=0.0033, P=0.8465). The Area Under Curve (AUC) of IL-6 for diagnosing psittacosis pneumonia was 0.7929 (P=0.0041). Conclusion: Patients with psittacosis pneumonia exhibit distinct interleukin level changes, particularly in IL-2 and IL-6, compared to those with ordinary pneumonia. The correlation of IL-6 with PCT levels suggests its potential as a marker in assessing respiratory health conditions, which could be relevant for monitoring respiratory health in athletes, given the heightened susceptibility to respiratory issues in this group (AU)

Dammarane-type triterpenoid saponins isolated from Gynostemma pentaphyllum ameliorate liver fibrosis via agonizing PP2Cα and inhibiting deposition of extracellular matrix.

Gypenosides, structurally analogous to ginsenosides and derived from a sustainable source, are recognized as the principal active compounds found in Gynostemma pentaphyllum, a Chinese medicinal plant used in the treatment of the metabolic syndrome. By bioactive tracking isolation of the plants collected from different regions across China, we obtained four new gypenosides (1-4), together with nine known gypenosides (5-13), from the methanol extract of the plant. The structures of new gypenosides were elucidated by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectra, complemented by chemical degradation experiments. Through comprehensive evaluation involving COL1A1 promoter assays and PP2Cα activity assays, we established a definitive structure-activity relationship for these dammarane-type triterpenoids, affirming the indispensability of the C-3 saccharide chain and C-17 lactone ring in effectively impeding extracellular matrix (ECM) deposition within hepatic stellate cells. Further in vivo study on the CCl4-induced liver damage mouse model corroborated that compound 5 significantly ameliorated the process of hepatic fibrosis by oral administration. These results underscore the potential of dammarane-type triterpenoids as prospective anti-fibrotic leads and highlight their prevalence as key molecular frameworks in the therapeutic intervention of chronic hepatic disorders.

Tough and strong sustainable thermoplastic elastomers nanocomposite with self-assembly of SI-ATRP modified cellulose nanofibers.

The ingenious design of sustainable thermoplastic elastomers (STPEs) is of great significance for the goal of the sustainable development. However, the preparation of STPEs with good mechanical performance is still complicated and challenging. Herein, to achieve a simple preparation of STPEs with strong mechanical properties, two biobased monomers (tetrahydrofurfuryl methacrylate (THFMA) and lauryl methacrylate (LMA)) were copolymerized into poly (THFMA-co-LMA) (PTL) and grafted onto TEMPO oxidized cellulose nanofiber (TOCN) via one-pot surface-initiated atom transfer radical polymerization (SI ATRP). The grafting modified TOCN could be self-assembled into nano-enhanced phases in STPEs, which are conducive to the double enhancement of the strength and toughness of the STPEs, and the size of nano-enhanced phases is mainly affected by TOCN fiber length and molecular weight of grafting chains. Especially, with the addition of 7 wt% TOCN, tensile strength, tensile strain, toughness, and glass transition temperature (Tg) of TOCN based STPEs (TOCN@PTL) exhibited 140 %, 36 %, 215 %, and 6.8 °C increase respectively, which confirmed the leading level in the field of bio-based elastomers. In general, this work constitutes a proof for the chemical modification and self-assembly behavior of TOCN by one-pot SI ATRP, and provides an alternative strategy for the preparation of high-performance STPEs.

SND1, a novel co-activator of HIF1α, promotes tumor initiation in PyMT-induced breast tumor.

The multifunctional protein staphylococcal nuclease domain-containing protein 1 (SND1) is conserved and has been implicated in several aspects of tumor development, such as proliferation, epithelial-mesenchymal transition, and immune evasion. Despite this, the precise role of SND1 in the initiation and metastasis of mammary gland tumors remains largely unexplored. In this study, we utilized a mouse model of breast tumors induced by polyomavirus middle T antigen (PyMT) to demonstrate that the knockout of SND1 significantly delayed the onset of primary mammary tumor formation induced by PyMT. Histological staining and cytometric analysis were conducted to confirm the reduction of tumor-initiating cells and lung metastasis following depletion of SND1. Additionally, our findings demonstrate that enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), a crucial epigenetic modifier implicated in PyMT-induced breast tumors, serves as an essential mediator of SND1-promoted primary mammary tumor formation. Mechanistic investigations revealed that SND1 functions as a transcriptional co-activator of hypoxia-inducible factor 1 subunit alpha (HIF1α), thereby regulating the downstream target gene EZH2 and promoting tumorigenesis. Overall, this study provides novel insights into the role of SND1 as a co-activator of HIF1α in the acceleration of PyMT-induced spontaneous breast tumor formation through the promotion of EZH2 transcription. The findings provide novel insights into the relationship between SND1 and the formation of tumor-initiating cells.

Gypenosides Synergistically Reduce the Extracellular Matrix of Hepatic Stellate Cells and Ameliorate Hepatic Fibrosis in Mice.

Liver fibrosis resulting from chronic liver damage is becoming one of the major threats to health worldwide. Active saponin constituents isolated from Gynostemma pentaphyllum were found to possess a protective effect in liver diseases. Here, we obtained a naturally abundant gypenoside, XLVI, and evaluated its liver protection activity in both animal and cellular models. The results showed that it ameliorated acute and chronic liver injuries and lightened the process of fibrogenesis in vivo. XLVI can inhibit TGF-ß-induced activation of hepatic stellate cells and ECM deposition in vitro. The underlying mechanism study verified that it upregulated the protein expression of protein phosphatase 2C alpha and strengthened the vitality of the phosphatase together with a PP2Cα agonist gypenoside NPLC0393. These results shed new light on the molecular mechanisms and the potential therapeutic function of the traditional herb Gynostemma pentaphyllum in the treatment of liver fibrosis.

Design, synthesis, and biological evaluation of a series of indolone derivatives as novel FLT3 inhibitors for the treatment of acute myeloid leukemia.

FLT3-ITD mutant has been extensively studied as a drug discovery target for acute myeloid leukemia. Based on our previous discovered FLT3 inhibitor (2), a series of urea group based indolone derivatives were designed, synthesized, and biological evaluated as novel FLT3 inhibitors for the treatment of FLT3-ITD positive AML. Among them, compound LC-3 exhibited potent inhibitory effects against FLT3 (IC50 = 8.4 nM) and significantly inhibited the proliferation of FLT3-ITD positive AML cells MV-4-11 (IC50 = 5.3 nM). In the cellular context, LC-3 strongly inhibited FLT3-mediated signaling pathways and induced cellular apoptosis by arresting cell cycle in G1 phase. In the in vivo studies, LC-3 significantly suppressed the tumor growth on MV-4-11 xenograft models (10 mg/kg/day, TGI = 92.16%) without exhibiting obvious toxicity. These results suggested that compound LC-3 might be a potential drug candidate for FLT3-ITD positive AML.

Identification of Bone Morphometric Protein-Related Hub Genes and Construction of a Transcriptional Regulatory Network in Patients With Ossification of the Ligamentum Flavum.

STUDY DESIGN: Basic science laboratory study. OBJECTIVE: To identify hub genes related to bone morphogenetic proteins (BMPs) in the ossification of the ligamentum flavum (OLF) and analyze their functional characteristics. SUMMARY OF BACKGROUND DATA: The exact etiology and pathologic mechanism of OLF remain unclear. BMPs are pleiotropic osteoinductive proteins that may play a critical role in this condition. MATERIALS AND METHODS: The GSE106253 and GSE106256 data sets were downloaded from the Gene Expression Omnibus database. The messenger RNA (mRNA) and long noncoding RNA expression profiles were obtained from GSE106253. The microRNA expression profiles were obtained from GSE106256. Differentially expressed genes were identified between OLF and non-OLF groups and then intersected with BMP-related genes to obtain differentially expressed BMP-related genes. The least absolute shrinkage selection operator and support vector machine recursive feature elimination were used to screen hub genes. Furthermore, a competing endogenous RNA network was constructed to explain the expression regulation of the hub genes in OLF. Finally, the protein and mRNA expression levels of the hub genes were verified using Western blot and real-time polymerase chain reaction, respectively. RESULTS: We identified 671 Differentially expressed genes and 32 differentially expressed BMP-related genes. Hub genes ADIPOQ , SCD , SCX , RPS18 , WDR82 , and SPON1 , identified through the least absolute shrinkage selection operator and support vector machine recursive feature elimination analyses, showed high diagnostic values for OLF. Furthermore, the competing endogenous RNA network revealed the regulatory mechanisms of the hub genes. Real-time polymerase chain reaction showed that the mRNA expression of the hub genes was significantly downregulated in the OLF group compared with the non-OLF group. Western blot showed that the protein levels of ADIPOQ, SCD, WDR82 , and SPON1 were significantly downregulated, whereas those of SCX and RPS18 were significantly upregulated in the OLF group compared with the non-OLF group. CONCLUSION: This study is the first to identify BMP-related genes in OLF pathogenesis through bioinformatics analysis. ADIPOQ , SCD , SCX , RPS18 , WDR82 , and SPON1 were identified as hub genes for OLF. The identified genes may serve as potential therapeutic targets for treating patients with OLF.