Enhancing microbial superoxide generation and conversion to hydroxyl radicals for enhanced bioremediation using iron-binding ligands.

Harnessing bacteria for superoxide production in bioremediation holds immense promise, yet its practical application is hindered by slow production rates and the relatively weak redox potential of superoxide. This study delves into a cost-effective approach to amplify superoxide production using an Arthrobacter strain, a prevalent soil bacterial genus. Our research reveals that introducing a carbon source along with specific iron-binding ligands, including deferoxamine (DFO), diethylenetriamine pentaacetate (DTPA), citrate, and oxalate, robustly augments microbial superoxide generation. Moreover, our findings suggest that these iron-binding ligands play a pivotal role in converting superoxide into hydroxyl radicals by modulating the electron transfer rate between Fe(III)/Fe(II) and superoxide. Remarkably, among the tested ligands, only DTPA emerges as a potent promoter of this conversion process when complexed with Fe(III). We identify an optimal Fe(III) to DTPA ratio of approximately 1:1 for enhancing hydroxyl radical production within the Arthrobacter culture. This research underscores the efficacy of simultaneously introducing carbon sources and DTPA in facilitating superoxide production and its subsequent conversion to hydroxyl radicals, significantly elevating bioremediation performance. Furthermore, our study reveals that DTPA augments superoxide production in cultures of diverse soils, with various soil microorganisms beyond Arthrobacter identified as contributors to superoxide generation. This emphasizes the universal applicability of DTPA across multiple bacterial genera. In conclusion, our study introduces a promising methodology for enhancing microbial superoxide production and its conversion into hydroxyl radicals. These findings hold substantial implications for the deployment of microbial reactive oxygen species in bioremediation, offering innovative solutions for addressing environmental contamination challenges.

Possible mechanisms for adverse effects on zebrafish sperm and testes associated with low-level chronic PFOA exposure.

Perfluorooctanoic acid (PFOA), which is widely used during the manufacturing of fluoropolymer coatings and polytetrafluoroethylene, is now a widespread pollutant in the environment and within the human body. This study used zebrafish, an aquatic model species, to investigate how low levels of chronic PFOA exposure affect the reproductive system. The results of the experiments in which zebrafish were exposed to 414 ng/L or 4140 ng/L for 60 days showed a variety of adverse effects on testicular tissue and sperm, including dose-dependent changes in plasma estradiol and testosterone levels, various sperm malformations, decreased sperm motility and concentration, and PFOA-induced oxidative stress and testicular damage with increased rates of apoptosis. In addition, offspring of the zebrafish that had been exposed to PFOA were characterized by increased malformation and mortality. Subsequent transcriptional analyses of the male gonads revealed the significant activation of oxidative stress bioprocesses and immuno-inflammatory signaling pathways, along with the dysregulation of reproductive bioprocesses. In conclusion, low-level chronic exposure to PFOA affects both the reproductive performance of adults and the development of offspring; the mechanisms for these adverse effects involve alterations in several molecular pathways that may be involved in PFOA-induced oxidative stress and reproductive abnormalities. The presented data can be used to assess the ecotoxicity of PFOA to the male reproductive system at environmentally-relevant concentrations.

The association of preoperative radiotherapy and surgery for AJCC stage I-III rectal adenocarcinoma: a population-based study.

BACKGROUND: With the increasing application of neoadjuvant therapy in rectal adenocarcinoma, there remain many controversies in clinical practical applications. Preoperative radiotherapy (PR) can limit the surgical plane and potentially affect the quality of surgical treatment. This study aimed to investigate the potential impact of PR on the surgical quality of rectal adenocarcinoma. METHODS: This retrospective study analyzed the clinicopathological data from 6,585 AJCC stage I-III rectal adenocarcinoma in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Kaplan-Meier survival analysis and multivariate Cox proportional were used to assess the impact of PR on survival. Propensity score matching (PSM) was employed to balance the baseline covariates between the PR and non-PR groups and to compare postoperative pathological differences. RESULTS: After PSM, PR did not improve overall survival (OS) in stages I (p = 0.33), II (p = 0.37), and III (p = 0.14) patients. Multivariate Cox analysis indicated that PR was not an independent prognostic factor for patients. Restricted cubic spline (RCS) analysis demonstrated a nonlinear negative correlation between OS hazard ratios and both circumferential resection margin (CRM) and lymph node evaluation (LNE). Compared to the non-PR group, patients in the PR group had lower tumor deposits (TD) (p < 0.001), positive CRM (p = 0.191), and perineural invasion (PNI) (p = 0.001). CONCLUSION: PR is not an independent prognostic factor for rectal adenocarcinoma patients. However, PR can reduce the likelihood of TD, CRM, and PNI, thereby potentially influencing the quality of surgery.

Prevalence and risk factors for refractive error in older adults in eight ethnicities in China: The China national health survey.

Purpose: This study aimed to investigate the prevalence of refractive error (RE) and risk factors for myopia among older adults in the Han and various minority ethnic groups across seven provinces in China. Methods: This cross-sectional study forms a part of the ophthalmic dataset of the China National Health Survey (CNHS). Face-to-face interviews and ophthalmic examinations were conducted in seven provinces located in western and northern China. The age- and sex-adjusted prevalence of RE among Han and seven other ethnic groups aged 50-80 years were compared. A mixed-effects model was used to identify the risk factors associated with RE. Results: A total of 12,902 participants, including 8800 Han and 4102 from ethnic minorities, were included in the study. The age- and sex-adjusted prevalence of myopia, high myopia, hyperopia, and astigmatism ranged from 15.3 % (Manchu) to 22.9 % (Han), 0.2 % (Yugur) to 2.8 % (Han), 21.6 % (Tibetan) to 48.9 % (Uyghur), and 38.7 % (Yi) to 57.5 % (Manchu) across different ethnicities, respectively. Compared to the Han population, the Mongolian (odds ratios (OR) 0.62, 95 % confidence interval (CI) 0.46-0.84, p = 0.002), Tibetan (OR 0.66, 95 % CI 0.52-0.85, p = 0.001), Uyghur (OR 0.63, 95 % CI 0.49-0.80, p < 0.001), Yi (OR 0.65, 95 % CI 0.46-0.92, p = 0.014), and Yugur (OR 0.65, 95 % CI 0.50-0.85, p = 0.001) ethnicities were less likely to have myopia. There was no significant difference in the prevalence of myopia between the Manchu, Korean, and Han ethnic groups. Factors associated with a lower prevalence of myopia included rural residence (p < 0.001), a body mass index (BMI) > 18.5 kg/m2 (all p < 0.001), residence in higher latitude areas (p = 0.020), and a history of smoking (p = 0.002 in the past smoking group, p = 0.031 in the current smoking group). The Mongolian (p = 0.006) and Yugur (p = 0.007) populations, participants living in rural areas (p = 0.012), and those with a BMI >24 kg/m2 (p = 0.038 in the >24.0 ≤ 27.0 kg/m2 group or p = 0.041 in the >27.0 kg/m2 group) were less likely to have high myopia. Factors associated with a higher prevalence of hyperopia included older age (all p < 0.001), rural residence (p = 0.039), higher latitude areas (p = 0.031), smoking history (p = 0.040), and Mongolian (p = 0.001), Uyghur (p < 0.001), Yi (p < 0.001), and Yugur (p = 0.002) ethnicities. Conversely, the Manchu population (p = 0.004) and individuals with higher education levels than illiteracy (p = 0.024 or p < 0.001) were less likely to have hyperopia. Conclusions: Myopia affected more than one-fifth of the older adults in the Han population in this survey. Significant differences in the prevalence of RE were observed between minority ethnicities and Han individuals, except for the Manchu and Korean groups.

Causal Inference Meets Deep Learning: A Comprehensive Survey.

Deep learning relies on learning from extensive data to generate prediction results. This approach may inadvertently capture spurious correlations within the data, leading to models that lack interpretability and robustness. Researchers have developed more profound and stable causal inference methods based on cognitive neuroscience. By replacing the correlation model with a stable and interpretable causal model, it is possible to mitigate the misleading nature of spurious correlations and overcome the limitations of model calculations. In this survey, we provide a comprehensive and structured review of causal inference methods in deep learning. Brain-like inference ideas are discussed from a brain-inspired perspective, and the basic concepts of causal learning are introduced. The article describes the integration of causal inference with traditional deep learning algorithms and illustrates its application to large model tasks as well as specific modalities in deep learning. The current limitations of causal inference and future research directions are discussed. Moreover, the commonly used benchmark datasets and the corresponding download links are summarized.

Research progress in the mechanisms and functions of specialized pro-resolving mediators in neurological diseases.

The nervous system interacts with the immune system through a variety of cellular regulators, signaling pathways, and molecular mechanisms. Disruptions in these interactions lead to the development of multiple neurological diseases. Recent studies have identified that specialized pro-resolving mediators (SPMs) play a regulatory role in the neuroimmune system. This study reviews recent research on the function of SPMs in the inflammatory process and their association with the nervous system. The review aims to provide new perspectives for studying the pathogenesis of neurological diseases and identify novel targets for clinical therapy.

Case report: is necrotizing fasciitis in a rectal cancer patient after targeted systemic therapy related to the tumor site? - evidence from a hepatocellular carcinoma patient.

Necrotizing fasciitis (NF) is a rare and life-threatening serious infectious disease, characterized by acute onset and rapid progress, leading to extensive necrosis of skin, soft tissue as well as fascia by a variety of aerobic and anaerobic bacteria, localized on external genitalia, scrotum, groin and perianal areas in males. There exist numerous common etiologies for NF, yet NF induced by malignant neoplasms is exceedingly rare. Several studies have reported that NF may be associated with tumor site (rectal/sigmoid colon cancer) and blood supply dysfunction caused by targeted therapy drugs (bevacizumab, aflibercept, ramucirumab). The perforation of colorectal cancer poses a unique risk factor for NF. However, in our two cases, the patient with rectal cancer received CapeOX (oxaliplatin + capecitabine) + bevacizumab + tislelizumab for 3 cycles without perforation but did develop NF. One month after debridement, the patient continued immunotherapy with tislelizumab alone for the fourth cycle and maintained for an additional 3 cycles without any recurrence of NF. Therefore, does the occurrence of NF correlate with the tumor site (rectum) and targeted immunotherapy? Another patient with hepatocellular carcinoma also developed NF after receiving 2 cycles of lenvatinib + sintilimab treatment. The third cycle of sintilimab immunotherapy was administered on the 13th day after operation, which was subsequently maintained for an additional 2 cycles without recurrence of NF. The absence of a direct correlation between hepatocellular carcinoma and rectal tumor location as well as immunotherapy, suggests that NF may be closely linked to targeted therapy.

The Biological Characteristics of Mycobacterium Phage Henu3 and the Fitness Cost Associated with Its Resistant Strains.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is an infectious disease that seriously affects human life and health. Despite centuries of efforts to control it, in recent years, the emergence of multidrug-resistant bacterial pathogens of M. tuberculosis due to various factors has exacerbated the disease, posing a serious threat to global health. Therefore, a new method to control M. tuberculosis is urgently needed. Phages, viruses that specifically infect bacteria, have emerged as potential biocontrol agents for bacterial pathogens due to their host specificity. In this study, a mycobacterium phage, Henu3, was isolated from soil around a hospital. The particle morphology, biological characteristics, genomics and phylogeny of Henu3 were characterized. Additionally, to explore the balance between phage resistance and stress response, phage Henu3-resistant strains 0G10 and 2E1 were screened by sequence passage and bidirectional validation methods, which significantly improved the sensitivity of phage to antibiotics (cefotaxime and kanamycin). By whole-genome re-sequencing of strains 0G10 and 2E1, 12 genes involved in cell-wall synthesis, transporter-encoded genes, two-component regulatory proteins and transcriptional regulatory factor-encoded genes were found to have mutations. These results suggest that phage Henu3 has the potential to control M. tuberculosis pathogens, and phage Henu3 has the potential to be a new potential solution for the treatment of M. tuberculosis infection.

Insights into the Preparation of and Evaluation of the Bactericidal Effects of Phage-Based Hydrogels.

The rise of antibiotic-resistant strains demands new alternatives in antibacterial treatment. Bacteriophages, with their precise host specificity and ability to target and eliminate bacteria safely, present a valuable option. Meanwhile, hydrogels, known for their excellent biodegradability and biocompatibility, serve as ideal carriers for bacteriophages. The combination of bacteriophages and hydrogels ensures heightened phage activity, concentration, controlled release, and strong antibacterial properties, making it a promising avenue for antibacterial treatment. This article provides a comprehensive review of different crosslinking methods for phage hydrogels, focusing on their application in treating infections caused by various drug-resistant bacteria and highlighting their effective antibacterial properties and controlled release capabilities.

Case report: A clinical report of photodynamic neoadjuvant combined with fluorescent laparoscopic localization robotic surgery for the treatment of patients with advanced colorectal cancer combined with obstruction.

The incidence of colorectal cancer is relatively high in our country, with the majority of patients being diagnosed at an advanced stage. For individuals with advanced-stage colorectal cancer, conversion or neoadjuvant therapy is frequently necessitated to facilitate surgical intervention and achieve a curative effect. And about 10% to 30% of colon cancer patients are complicated with intestinal obstruction. Surgical intervention remains the primary treatment for managing intestinal obstructions, albeit with a considerable risk of perioperative mortality and an increased likelihood of postoperative complications. PDT, as a neoadjuvant treatment for colon cancer, can shrink the local tumor and relieve obstruction, and is effective in colon cancer combined with obstruction. Robotic surgery has the advantages of high stability and low trauma, and compared with laparoscopic colon cancer surgery, robotic surgery can achieve better results. Fluorescent laparoscopic clarifies the location and size of the tumor lesion, allowing for greater precision when removing colon cancer lesions in robotic surgery. Therefore, in the treatment of colon cancer, PDT can offer an opportunity for surgery after relieving obstruction in patients with obstructive colon cancer. Additionally, when combined with fluorescent laparoscopic robotic colon cancer surgery, it provides a novel treatment approach for patients with obstructive colon cancer. Preoperative photodynamic neoadjuvant therapy combined with robotic colon cancer surgery has not yet been reported. Here, we report a case of colon cancer with obstruction, preoperative TNM stage was T4N1, and the lesion had caused intestinal stenosis. After four sessions of PDT, the patient's intestinal lumen was unobstructed and the lesion had regressed. After evaluation, fluorescent laparoscopic localization and visualization of lymph nodes combined with robotic colon cancer resection were performed. Postoperative pathology showed that the patient's tumor regression grade was grade 1. The patient's tumor was completely resected with good resection effect. No tumor invasion was found on both sides of the resection margin, and the patient did not relapse after surgery.

Polyunsaturated Fatty Acids as Potential Treatments for COVID-19-Induced Anosmia.

Some individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experience anosmia, or loss of smell. Although the prevalence of anosmia has decreased with the emergence of the Omicron variant, it remains a significant concern. This review examines the potential role of polyunsaturated fatty acids (PUFAs), particularly omega-3 PUFAs, in treating COVID-19-induced anosmia by focusing on the underlying mechanisms of the condition. Omega-3 PUFAs are known for their anti-inflammatory, neuroprotective, and neurotransmission-enhancing properties, which could potentially aid in olfactory recovery. However, study findings are inconsistent. For instance, a placebo-controlled randomized clinical trial found no significant effect of omega-3 PUFA supplementation on olfactory recovery in patients with COVID-19-induced anosmia. These mixed results highlight the limitations of existing research, including small sample sizes, lack of placebo controls, short follow-up periods, and combined treatments. Therefore, more rigorous, large-scale studies are urgently needed to definitively assess the therapeutic potential of omega-3 PUFAs for olfactory dysfunction. Further research is also crucial to explore the broader role of PUFAs in managing viral infections and promoting sensory recovery.

Long sleep duration is associated with abdominal aortic calcification among male adults with chronic kidney disease: NHANES 2013-2014.

There are no studies exploring the correlation between sleep duration and abdominal aortic calcification (AAC). This study aims to investigate this relationship and its significance. Additionally, given the higher prevalence of sleep disorders and AAC in patients with chronic kidney disease (CKD), we conducted further studies in this population. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014. Sleep duration was assessed by a sleep questionnaire and categorized into 2-5, 6-8, and ≥ 9 h. The AAC-24 score is determined using the Kauppila scoring system and used for AAC assessment. Multivariable linear and logistic regression analysis were used to explore the relationship between sleep duration and AAC. Among the 2,996 participants, 14.29% reported nightly short sleep (2-5 h), 77.64% reported intermediate sleep (6-8 h), and 8.08% reported long sleep (≥ 9 h). After adjusting for potential confounding factors, among male participants with CKD, long sleep (≥ 9 h) significantly increased AAC-24 scores compared with intermediate sleep (6-8 h) (ß: 2.12; 95% CI: 0.75, 3.50), and the risk of severe AAC (SAAC) was increased by 1.55 times (OR: 2.55; 95% CI: 1.02, 6.36). And among female CKD and non-CKD participants, sleep duration was not associated with AAC. Long sleep duration increases the risk of AAC among male adults with CKD. Prospective studies are needed to confirm this finding.

Leveraging programmed cell death patterns to predict prognosis and therapeutic sensitivity in OSCC.

OBJECTIVES: Intricate associations between programmed cell death (PCD) and cancer development and treatment outcomes have been increasingly appreciated. Here, we integrated 12 PCD patterns to construct a novel biomarker, cell death index (CDI), for oral squamous cell carcinoma (OSCC) prognostication and therapeutic prediction. MATERIALS AND METHODS: Univariate Cox regression, Kaplan-Meier survival, and LASSO analyses were performed to construct the CDI. A nomogram combining CDI and selected clinicopathological parameters was established by multivariate Cox regression. The associations between CDI and immune landscape and therapeutic sensitivity were estimated. Single-cell RNA-seq data of OSCC was used to infer CDI genes in selected cell types and determine their expression along cell differentiation trajectory. RESULTS: Ten selected PCD genes derived a novel prognostic signature for OSCC. The predictive prognostic performance of CDI and nomogram was robust and superior across multiple independent patient cohorts. CDI was negatively associated with tumor-infiltrating immune cell abundance and immunotherapeutic outcomes. Moreover, scRNA-seq data reanalysis revealed that GSDMB, IL-1A, PRKAA2, and SFRP1 from this signature were primarily expressed in cancer cells and involved in cell differentiation. CONCLUSIONS: Our findings established CDI as a novel powerful predictor for prognosis and therapeutic response for OSCC and suggested its potential involvement in cancer cell differentiation.

Predictive Model Building for Aggregation Kinetics Based on Molecular Dynamics Simulations of an Antibody Fragment.

Computational methods including machine learning and molecular dynamics simulations have strong potential to characterize, understand, and ultimately predict the properties of proteins relevant to their stability and function as therapeutics. Such methods would streamline the development pathway by minimizing the current experimental testing required for many protein variants and formulations. The molecular understanding of thermostability and aggregation propensity has advanced significantly along with predictive algorithms based on the sequence-level or structural-level information on a protein. However, these approaches focus largely on a comparison of protein sequence variations to correlate the properties of proteins to their stability, solubility, and aggregation propensity. For therapeutic protein development, it is of equal importance to take into account the impact of the formulation conditions to elucidate and predict the stability of the antibody drugs. At the macroscopic level, changing temperature, pH, ionic strength, and the addition of excipients can significantly alter the kinetics of protein aggregation. The mechanisms controlling aggregation kinetics have been traced back to a combination of molecular features, including conformational stability, partial unfolding to aggregation-prone states, and the colloidal stability governed by surface charges and hydrophobicity. However, very little has been done to evaluate these features in the context of protein dynamics in different formulations. In this work, we have combined a range of molecular features calculated from the Fab A33 protein sequence and molecular dynamics simulations. Using the power of advanced, yet interpretable, statistical tools, it has been possible to uncover greater insights into the mechanisms behind protein stability, validating previous findings, and also develop models that can predict the aggregation kinetics within a range of 49 different solution conditions.

Apo E protein and related markers show the prognosis of stress urinary incontinence rats treated with modified Buzhong Yiqi Decoction.

Stress urinary incontinence (SUI) is a common disease that seriously affects the quality of life of patients. In recent years, studies have shown that apolipoprotein E (ApoE) plays a role in neuroprotection and repair, but its specific role in SUI remains unclear. The aim of this study was to investigate the effect of macromolecular protein ApoE related markers on the prognosis of rats with SUI treated by modified Buzhong Yiqi Decoction (MBZYQD), in order to provide a new target for the treatment of SUI. Healthy rats were selected to establish a SUI model and divided into groups. The levels of ApoE related metabolites in blood of rats were detected by Metabolomics analysis and Lipidomics analysis. The urine leakage point pressure (LPP) were compared in each group, and the therapeutic effect of MBZYQD was evaluated. Compared with the model group, the LPP of rats in MBZYQD supplemented group was significantly higher. Compared with the control group, the LPP of MBZYQD was not statistically significant before and after treatment. The macromolecular protein ApoE may plays a key role in the treatment of SUI by MBZYQD, which can improve symptoms by regulating lipid metabolism repair.

Super-Enhancer Driven LIF/LIFR-STAT3-SOX2 Regulatory Feedback Loop Promotes Cancer Stemness in Head and Neck Squamous Cell Carcinoma.

Super-enhancers (SEs) have been recognized as key epigenetic regulators underlying cancer stemness and malignant traits by aberrant transcriptional control and promising therapeutic targets against human cancers. However, the SE landscape and their roles during head and neck squamous cell carcinoma (HNSCC) development especially in cancer stem cells (CSCs) maintenance remain underexplored yet. Here, we identify leukemia inhibitory factor (LIF)-SE as a representative oncogenic SE to activate LIF transcription in HNSCC. LIF secreted from cancer cells and cancer-associated fibroblasts promotes cancer stemness by driving SOX2 transcription in an autocrine/paracrine manner, respectively. Mechanistically, enhancer elements E1, 2, 4 within LIF-SE recruit SOX2/SMAD3/BRD4/EP300 to facilitate LIF transcription; LIF activates downstream LIFR-STAT3 signaling to drive SOX2 transcription, thus forming a previously unknown regulatory feedback loop (LIF-SE-LIF/LIFR-STAT3-SOX2) to maintain LIF overexpression and CSCs stemness. Clinically, increased LIF abundance in clinical samples correlate with malignant clinicopathological features and patient prognosis; higher LIF concentrations in presurgical plasma dramatically diminish following cancer eradication. Therapeutically, pharmacological targeting LIF-SE-LIF/LIFR-STAT3 significantly impairs tumor growth and reduces CSC subpopulations in xenograft and PDX models. Our findings reveal a hitherto uncharacterized LIF-SE-mediated auto-regulatory loop in regulating HNSCC stemness and highlight LIF as a novel noninvasive biomarker and potential therapeutic target for HNSCC.

Data Collection and Management of mHealth, Wearables, and Internet of Things in Digital Behavioral Health Interventions With the Awesome Data Acquisition Method (ADAM): Development of a Novel Informatics Architecture.

Unlabelled: The integration of health and activity data from various wearable devices into research studies presents technical and operational challenges. The Awesome Data Acquisition Method (ADAM) is a versatile, web-based system that was designed for integrating data from various sources and managing a large-scale multiphase research study. As a data collecting system, ADAM allows real-time data collection from wearable devices through the device's application programmable interface and the mobile app's adaptive real-time questionnaires. As a clinical trial management system, ADAM integrates clinical trial management processes and efficiently supports recruitment, screening, randomization, data tracking, data reporting, and data analysis during the entire research study process. We used a behavioral weight-loss intervention study (SMARTER trial) as a test case to evaluate the ADAM system. SMARTER was a randomized controlled trial that screened 1741 participants and enrolled 502 adults. As a result, the ADAM system was efficiently and successfully deployed to organize and manage the SMARTER trial. Moreover, with its versatile integration capability, the ADAM system made the necessary switch to fully remote assessments and tracking that are performed seamlessly and promptly when the COVID-19 pandemic ceased in-person contact. The remote-native features afforded by the ADAM system minimized the effects of the COVID-19 lockdown on the SMARTER trial. The success of SMARTER proved the comprehensiveness and efficiency of the ADAM system. Moreover, ADAM was designed to be generalizable and scalable to fit other studies with minimal editing, redevelopment, and customization. The ADAM system can benefit various behavioral interventions and different populations.

The HOXC10/NOD1/ERK axis drives osteolytic bone metastasis of pan-KRAS-mutant lung cancer.

While KRAS mutation is the leading cause of low survival rates in lung cancer bone metastasis patients, effective treatments are still lacking. Here, we identified homeobox C10 (HOXC10) as a lynchpin in pan-KRAS-mutant lung cancer bone metastasis. Through RNA-seq approach and patient tissue studies, we demonstrated that HOXC10 expression was dramatically increased. Genetic depletion of HOXC10 preferentially impeded cell proliferation and migration in vitro. The bioluminescence imaging and micro-CT results demonstrated that inhibition of HOXC10 significantly reduced bone metastasis of KRAS-mutant lung cancer in vivo. Mechanistically, the transcription factor HOXC10 activated NOD1/ERK signaling pathway to reprogram epithelial-mesenchymal transition (EMT) and bone microenvironment by activating the NOD1 promoter. Strikingly, inhibition of HOXC10 in combination with STAT3 inhibitor was effective against KRAS-mutant lung cancer bone metastasis by triggering ferroptosis. Taken together, these findings reveal that HOXC10 effectively alleviates pan-KRAS-mutant lung cancer with bone metastasis in the NOD1/ERK axis-dependent manner, and support further development of an effective combinatorial strategy for this kind of disease.