Superaerophilic/Superaerophobic NiFe-LDHs Electrode for Enhancing Overall Water Splitting in Alkaline Media.

Overall water splitting, as a critical approach to producing green hydrogen, is greatly impeded by the mass transfer of gaseous bubbles and dissolved gas molecules. Herein, a bifunctional superaerophilic/superaerophobic (SAL/SAB) NiFe layered-double-hydroxides (LDHs) electrode has been developed, which can drive H2 and O2 bubbles out of the reaction system by asymmetric Laplace pressure and accelerate dissolved gases diffusion through reducing their diffusion distance. Consequently, the SAL/SAB NiFe-LDHs electrode exhibits excellent HER activity with an overpotential of -76 mV at -10 mA cm-2 and outstanding oxygen evolution reaction activity with an overpotential of 253 mV at 100 mA cm-2. The bifunctional SAL/SAB NiFe-LDHs electrode is further utilized in overall water splitting, which can achieve 10 mA cm-2 with a cell voltage of 1.54 V. This work provides an efficient strategy to improve the efficiency of overall water splitting and can stimulate new electrode design in various gas-involved processes.

Immunotherapy strategies for EGFR-mutated advanced NSCLC after EGFR tyrosine-kinase inhibitors failure.

Background: This study aimed to investigate the efficacy of immunotherapy, as monotherapy or in combination, comparing to chemotherapy with or without anti-angiogenesis for advanced non-small cell lung cancer (NSCLC) patients progressing to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Methods: We retrospectively analyzed patients with advanced NSCLC harboring EGFR mutations who received immune checkpoint inhibitors (ICI) and/or chemotherapy after EGFR-TKIs failure at Shanghai Chest Hospital between Aug 2016 and Oct 2022. According to the subsequent immunotherapy regimen, the patients were assigned to ICI monotherapy (IM), IO plus anti-angiogenesis (IA), ICI plus chemotherapy (IC), ICI plus chemotherapy plus anti-angiogenesis (ICA). Eligible patients undergoing standard chemotherapy were assigned to chemotherapy plus anti-angiogenesis (CA) and chemotherapy alone (CM). Efficacy was evaluated according to the RECIST 1.1version, and calculated the objective response rate (ORR) and disease control rate (DCR). Survival curves were plotted using the Kaplan-Meier method, and the median progression-free survival (PFS) was calculated. Differences among survival curves of the six groups were assessed using the log-rank test. Results: A total of 237 advanced NSCLC patients with EGFR mutations were included in this study. Of the 160 patients who received immunotherapy, 57 received ICI monotherapy, 27 received ICI plus anti-angiogenesis therapy, 43 received ICI plus chemotherapy, and 33 received ICI plus anti-angiogenesis plus chemotherapy. 77 patients received standard chemotherapy, of which 30 received chemotherapy plus anti-angiogenesis and 47 received chemotherapy alone. Patients in ICA group showed significant longer PFS than IM (7.2 vs 1.9 months, P=0.011), IA (7.2 vs 4.8 months, P=0.009) and CM group (7.2 vs 4.4 months, P=0.005). There was no significant difference in PFS between the ICA and IC (7.2 vs 5.6 months, P=0.104) or CA (7.2 vs 6.7 months, P=0.959) group. Meanwhile, the ICA group showed the highest ORR and DCR (36.4% and 90.9%) compared to the other five groups. The IC group had a higher ORR than the IA and CA group (32.6% vs 7.4% vs 10.0%, respectively), but the DCR was comparable (79.1% vs 74.1% vs 76.7%, respectively). The ORR of the CM group was 6.4% and the DCR was 66.0%. IM group showed the lowest ORR and DCR (1.8% and 36.8%). Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 9 (27.3%) patients in the ICA group, 6 (20.0%) in the CA group, 7 (14.9%) in the CM group, 5 (11.6%) in the IC group, 5 (8.8%) in the IM group, and 2 (7.4%) in the IA group. Conclusion: NSCLC patients with positive EGFR mutations after EGFR-TKIs failure received subsequent immunotherapy plus anti-angiogenesis and chemotherapy are likely to have more benefits in ORR, DCR and mPFS.

Neoadjuvant Chemoimmunotherapy Increases Tumor Immune Lymphocytes Infiltration in Resectable Non-small Cell Lung Cancer.

BACKGROUND: Neoadjuvant chemoimmunotherapy treatment (NCIT) has achieved great success for non-small cell lung cancer (NSCLC); however, the intrinsic mechanism underlying this treatment remains unclear. METHODS: Thirty-two patients with stage IIA-IIIC NSCLC who underwent surgery after NCIT were included in this retrospective study. Multiplex immunofluorescence (mIF) staining and image analysis assays were performed on the samples collected before and after NCIT for each patient. RNA analyses was applied to confirm the mIF results. RESULTS: Among the enrolled patients, 14 achieved major pathological response or pathological complete response (pCR) and were defined as the 'response' group, whereas 18 patients did not respond well to NCIT and were defined as the 'nonresponse' group. The results of the mIF assays revealed an overall increase in tumor immune lymphocytes (TILs) after NCIT in the stroma area (p = 0.03) rather than the tumor area (p = 0.86). The percentage of CD8+ T cells and tertiary lymphoid structure counts in both the response and nonresponse groups increased significantly after NCIT compared with before NCIT. CD3+ T cells and FOXP3+ cells decreased significantly in the response group but remained unchanged or increased in the nonresponse group. A comparison of the response and nonresponse groups showed that CD3, FOXP3+ and CD8+/PD-1+ cells before NCIT may serve as predictors of the response to neoadjuvant immunotherapy. The RNA analyses confirmed the mIF results that TILs were elevated after NCIT. CONCLUSIONS: The infiltration of immune cells before NCIT was correlated with pathologic complete response, which enhanced the TILs as a promising predictor for selecting patients who were more likely to benefit from NCIT.

Relevant factors of posterior mandible lingual plate perforation during immediate implant placement: a virtual implant placement study using CBCT.

BACKGROUND: To explore the influence of cross-sectional type and morphological parameters at the mandibular molar sites on lingual plate perforation (LPP) during the immediate implant placement (IIP). METHODS: 181 implants were virtually placed in the mandibular molar sites on the cone beam computed tomography (CBCT). Each cross-section of the implantation site was divided into the Undercut (U)/Parallel (P)/Convex (C) types. Morphologically relevant parameters were measured on the cross-sections, including width of the upper end (Wb), width of the lower end (Wc), vertical height (V), angle between the natural crown axis and the alveolar bone axis (∠ß), LC depth (LCD), LC height, and angle between the horizontal line and the line connecting the most prominent point and the most concave point of lingual plate (∠α). Besides, the distance from the end of the virtual implant and the lingual bone plate of the cross-section (DIL) was calculated. Relationships between all the morphologically relevant parameters and the DIL were further analyzed. RESULTS: A total of 77 (42.5%) cross-sections were classified as U-type, which was the most common one, accounting for 63% of the second molar regions. All LPP cases and most of the nearly LPP (87.9%) cases occurred at the U-type cross-sections, and the relationship between the DIL and the morphological parameters can be expressed by a multivariate linear equation. CONCLUSIONS: The occurrence rate of U-type cross-sections in the second molar region was very high, and the risk of LPP should be considered during IIP. Except for the U-type, significant large LCD, small Wc, and large âˆ ß were the important relevant factors. CBCT and multivariate linear equations could help to assess the LPP risk and provide a reference for implant placement design pre-surgery.

Impact of KRAS Mutation Subtypes and Co-Occurring Mutations on Response and Outcome in Advanced NSCLC Patients following First-Line Treatment.

(1) Background: The purpose was to systematically assess the impact of KRAS subtypes and co-mutations on responses of first-line treatment and outcomes by genetic classification in advanced KRAS mutant NSCLC. (2) Methods: Molecular pathology was confirmed with NGS; Kaplan−Meier analysis and Cox multivariate model were used to analyze the efficacy of first-line treatment and prognosis in KRAS subgroups. (3) Results: Advanced KRAS mutant NSCLC was confirmed among 183 patients, who received first-line therapy. The most common KRAS subtype and co-mutation were G12C (29.5%) and TP53 (59.6%). ICIs/CHE group prolonged PFS to 16.9 m, vs. (CHE)4.6 m vs. (CHE/BEV)7.0 m (p < 0.0001); mOS (ICIs/CHE)37.1 m vs. (CHE)19.8 m vs. [CHE/BEV] 20.7 m (p = 0.024). PFS benefited to different degrees after first-line ICI-based treatment in each genetic classification. KRAS G12D even benefited from OS (p = 0.045). CHE/BEV prolonged mPFS of KRAS/STK11 co-mutation (p = 0.043), but decreased mPFS in G12A subtype (p = 0.026). Multivariate analysis indicated that heavy smoking history (≥20 pack-years) (HR = 0.45, p = 0.039) predicts optimistic prognosis; PS score 1 (HR = 3.604, p = 0.002) and KRAS/SMAD4 co-mutation (HR = 4.293, p = 0.027) remained as independent predictors of shorter OS. (4) Conclusions: First-line treatment with ICI benefited KRAS-mutant-NSCLC patients and resulted in non-negative predictive value for any genetic classification. Bevacizumab should be cautiously chosen for patients with KRAS G12A subtype but is recommended for KRAS/STK11 patients. KRAS/SMAD4 is a new co-mutation genotype that displayed independent risk prognostic factors in patients with advanced KRAS-mutant NSCLC.

Controlled release of silibinin in GelMA hydrogels inhibits inflammation by inducing M2-type macrophage polarization and promotes vascularization in vitro.

A dry socket is one of the most common complications after tooth extraction. The main etiologies are the loss of blood clots in the socket and the inflammation reaction caused by infection. Current studies on how to prevent dry sockets could not solve these two etiologies at the same time. Recent studies have demonstrated the anti-inflammation role of silibinin. In this study, silibinin was engineered into GelMA hydrogels (Sil-GelMA) with a concentration of 30 mM. The surface characteristics were observed by scanning electron microscopy and the successful loading of silibinin was detected by FTIR spectrometry. The Sil-GelMA hydrogels presented the sustained release ability of silibinin and slow degradation performance of GelMA. Furthermore, silibinin inhibited the inflammatory reaction by inducing M2-type macrophage polarization, promoting the secretion of anti-inflammatory factors (CD206, IL-10) and inhibiting the secretion of anti-inflammatory factors (IL-1ß, iNOS). Silibinin also increased the secretion of vascularization-related factor VEGF and promoted vascularization in vitro. This study suggested that the Sil-GelMA hydrogels not only had an anti-inflammatory effect, but also had the potential to promote vascularization. Based on these results, the Sil-GelMA hydrogels might provide a promising prospect for prevention of dry sockets in the future.

Extracellular vesicles derived from neural EGFL-Like 1-modified mesenchymal stem cells improve acellular bone regeneration via the miR-25-5p-SMAD2 signaling axis.

Stem cell based transplants effectively regenerate tissues; however, limitations such as immune rejection and teratoma formation prevent their application. Extracellular vesicles (EVs)-mediated acellular tissue regeneration is a promising alternative to stem cell based transplants. Although neural EGFL-like 1 (Nell1) is known to contribute to the osteogenic differentiation of bone marrow stem cells (BMSCs), it remains unknown whether EVs are involved in this process. Here, we present that EVs derived from Nell1-modified BMSCs (Nell1/EVs) have a stronger ability to promote BMSC osteogenesis owing to miR-25-5p downregulation. MiR-25-5p inhibits osteogenesis by targeting Smad2 and suppressing the SMAD and extracellular signal-related kinase 1 and 2 (ERK1/2) pathway activation. In addition, we demonstrate that the 3D-Nell1/EV-hydrogel system is beneficial for bone regeneration in vivo, probably stemming from a slow, continuous release and high concentration of EVs in the bone defect area. Thus, our results have shown the potential of Nell1/EVs as a novel acellular bone regeneration strategy. Mechanistically, the identification of miR-25-5p-SMAD2 signaling axis expands the knowledge of Nell1/EVs induced osteogenesis.

The relationship between different subtypes of KRAS and PD-L1 & tumor mutation burden (TMB) based on next-generation sequencing (NGS) detection in Chinese lung cancer patients.

Background: KRAS gene mutations are the most common driver oncogenes in non-small cell lung cancer (NSCLC). We conducted an analysis of the immunological characteristics including tumor mutation burden and programmed death-ligand 1 (PD-L1) expression of different subtypes of KRAS in 2880 KRAS-mutant NSCLC patients. Methods: A total of 2,880 patients with NSCLC were included in the study. Somatic mutation data were provided by Berry Oncology (Fujian, China), Geneplus BioTech (Beijing, China), Nanjing Geneseeq Technology Inc (Nanjing, China), and Burning Rock Biotech (Guangzhou, China). Z-scores were used to unify all data. SPSS 20.0 (SPSS, Chicago, IL, USA) software was used for statistical analyses. All scatter plots and boxplot maps were drawn using GraphPad Prism 8. Tumor mutation burden (TMB) expression was defined by the number of somatic mutations. The PD-L1 clone 22C3 pharmDx kit was used to measure the expression level of PD-L1. Mann-Whitney U test was used for statistical analysis. P value <0.05 was considered statistically significant. Results: We identified 2,880 patients with KRAS-mutant NSCLC. The percentage level of TMB and expression of PD-L1 was significantly decreased in KRAS Q61X-mutant lung cancer tissue and blood samples (n=162). The percentage level of TMB and expression of PD-L1 in KRAS G13X-mutant lung cancer specimens was significantly increased (n=190). Conclusions: The findings demonstrate a decreased level of TMB and expression of PD-L1 in KRAS Q61X-mutant lung cancer and the increased level of TMB and expression of PD-L1 in KRAS G13X-mutant lung cancer. Further work is needed to identify if the subtype of KRAS mutation could be a potential therapeutic biomarker in lung cancer patients with KRAS mutation. TMB data was consistently verified in tissue and blood samples and confirmed the feasibility of next-generation sequencing (NGS) verification in plasma samples. Our research may help to provide more individualized treatment options for NSCLC patients.

Tagrisso incremental therapy in a case of meningeal metastasis of lung cancer with EGFR mutation: a case report.

The advent of precision treatment for non-small cell lung cancer (NSCLC) has witnessed the discovery of epidermal growth factor receptor (EGFR) mutations. EGFR tyrosine kinase inhibitors (TKIs) have proven efficacy in treating patients with advanced lung cancer and can significantly prolong overall survival (OS). The incidence of advanced lung cancer with central nervous system (CNS) metastasis has increased significantly. Patients with EGFR mutations are more likely than wild-type patients to develop meningeal metastasis. Many questions still surround treatment-related decision-making for patients with TKI-sensitive mutations, as well as the optimal treatment strategy after progress with TKI treatment. Moreover, the accurate and timely diagnosis of meningeal metastasis and the treatment for patients with TKI-sensitive mutated meningeal metastases also need to be addressed. Here, we report the case of a patient who was diagnosed as stage IV NSCLC with EGFR 21 exon L858R mutation combined with EGFR 20 exon T790M mutation based on an elevated carcinoembryonic antigen (CEA) level (193 ng/mL) as the first symptom. After being diagnosed as meningeal metastasis by cerebrospinal fluid (CSF) cytology, the patient received a regular double dose of Tagrisso. The patient's progression-free survival (PFS) was extended by 7 months, and the OS reached more than 5 years, which is rare in clinical practice. This case suggests that: (I) meningeal metastases should be diagnosed based on clinical presentation, CSF examination, and magnetic resonance imaging (MRI); and (II) in patients with EGFR-mutant meningeal metastases, incremental targeted drug treatment should be considered a therapeutic strategy.

Durable Response to the Combination of Atezolizumab With Platinum-Based Chemotherapy in an Untreated Non-Smoking Lung Adenocarcinoma Patient With BRAF V600E Mutation: A Case Report.

BACKGROUND: Immune checkpoint inhibitor (ICPi) has become a major treatment in advanced non-small cell lung cancer (NSCLC) and demonstrated a clinical benefit for NSCLC patients with high programmed death ligand-1 (PD-L1) expression without EGFR/ALK/ROS1 drivers; however, the benefit in BRAF V600E NSCLC is so far unknown. Here, we report a case of prolonged tumor response to the combination of immunotherapy with chemotherapy in a non-smoking BRAF V600E NSCLC patient. MATERIALS AND METHODS: We verify a co-expression of BRAF V600E mutation and PD-L1 high expression more than 50% on formalin-fixed paraffin-embedded tumor sample of a newly diagnosed lung adenocarcinoma patient by immunohistochemistry and BRAF V600E/EGFR/ALK/ROS1 Mutations Detection Kit. The tissue and liquid biopsies were further subjected to next-generation sequencing (NGS) for identification of mutations with progression on immunotherapy and BRAF inhibitor (BRAFi). The patient had provided written informed consent and authorized the publication of clinical case. RESULTS: We demonstrate the case of 62-year-old female non-smoker with high PD-L1 expression and BRAF V600E mutated NSCLC. The progression-free survival (PFS) of first-line combination of atezolizumab with platinum-based chemotherapy and sequential second-line treatment with BRAFi Vemurafenib are 20 and 5.5 months, respectively. CONCLUSION: This case shows a durable response to ICPi in BRAF V600E non-smoking lung adenocarcinoma with PFS of 20 months under first-line atezolizumab plus chemotherapy treatment. The case supports the idea that the combination immunotherapy may be an attractive option for BRAF V600E mutated non-smoking NSCLC with high PD-L1 expression.

Integrated discovery of FOXO1-DNA stabilizers from marine natural products to restore chemosensitivity to anti-EGFR-based therapy for metastatic lung cancer.

The transcription factor forkhead box O1 (FOXO1) negatively regulates activated EGFR signaling by turning on the gene expression of tumor suppressor Kruppel-like factor 6. Here, we propose that the chemosensitivity to anti-EGFR-based lung cancer therapy can be restored by stabilization of the FOXO1-DNA complex architecture using small-molecule marine natural medicines. A synthetic protocol that integrates computational ligand-protein-DNA binding analysis and an experimental fluorescence binding assay was applied against a large library of structurally diverse, drug-like marine natural products to discover novel stabilizers of DNA-bound FOXO1 conformation. The screening utilized chemical similarity analysis to exclude structurally redundant compounds, and then carried out high-throughput molecular docking and computational binding analysis to identify potential marine natural product candidates. Consequently, eight commercially available hits were selected and tested in vitro, from which four marine natural product compounds (tanzawaic acid D, hymenidin, cribrostatin 6 and barbamide) were found to have high or moderate potency to selectively bind to the FOXO1 DNA-binding domain (DBD) in the presence of its cognate DNA partner. Atomistic molecular dynamics (MD) simulations revealed that the identified stabilizers do not directly interact with DNA; instead, they can effectively stabilize the free FOXO1 DBD domain in the DNA-bound conformation and thus promote the binding of FOXO1 to DNA.

Detection and correlation analysis of serum cytokines in non-small-cell lung cancer patients with bone and non-bone metastases.

OBJECTIVE: To detect and analyze 13 cytokines that may be related to bone metastasis in the serum of non-small-cell lung cancer (NSCLC) patients with bone metastases and NSCLC patients with non-bone metastases. PATIENTS AND METHODS: The Luminex LiquiChip system was used to detect the concentration of 13 cytokines that may be related to bone metastasis in the serum of 30 NSCLC patients with bone metastases and 30 with non-bone metastases. RESULTS: The concentration of insulin-like growth factor binding protein-3 (IGFBP-3) in the serum of NSCLC patients with bone metastases was obviously higher than in non-bone metastasis patients (P=0.014). The serum concentration of other cytokines showed no significant difference (P>0.05) between the two groups. The concentration of IGFBP-3 in the serum of the bone metastasis group was positively correlated to VEGF concentration (r=0.804, P=0.009) and monocyte chemotactic protein 1 (MCP-1) concentration (r=0.785, P=0.012), but had no correlation to other factors (P>0.05). No correlation was found between serum concentrations of cytokines in bone metastasis. Concentration of IGFBP-3 in the serum of bone metastasis patients was positively correlated to the presence or absence of pain at diagnosis (r=0.701, P=0.036) and performance status (PS) score (r=0.670, P=0.048), and correlated with the number of bone metastases, sex, age, pathological characteristics, T stage, and N stage (P>0.05). CONCLUSION: The findings of this study suggest important clinical implications to detect the concentration of IGFBP-3 in the serum of lung cancer patients so as to evaluate the diagnosis and degree of bone metastasis. Concentration of IGFBP-3 in the serum of bone metastasis patients was positively correlated to concentration of VEGF and MCP-1, which may be highly relevant for the development of new treatments for bone metastasis of lung cancer.

NF-κB-mediated miR-124 suppresses metastasis of non-small-cell lung cancer by targeting MYO10.

Recently, dysregulation of microRNAs plays a critical role in cancer metastasis. Here, an in vivo selection approach was used to generate highly aggressive NSCLC sub-cell lines followed by comparing the microRNAs expression using microarrays. miR-124 was notably deregulated in both highly invasive sub-cell lines and node-positive NSCLC specimens. Over-expression of miR-124 robustly attenuated migration and metastatic ability of the aggressive cells. MYO10 was subsequently identified as a novel functional downstream target of miR-124, and was up-regulated in node-positive NSCLC tissues. Knockdown of MYO10 inhibited cell migration, whereas forced MYO10 expression markedly rescued miR-124-mediated suppression of cell metastasis. Additionally, we found an activated NF-κB-centered inflammatory loop in the highly aggressive cells leading to down-regulation of miR-124. These results suggest that NF-κB-regulated miR-124 targets MYO10, inhibits cell invasion and metastasis, and is down-regulated in node-positive NSCLC.

A systematic profile of clinical inhibitors responsive to EGFR somatic amino acid mutations in lung cancer: implication for the molecular mechanism of drug resistance and sensitivity.

Human epidermal growth factor receptor (EGFR) has become a well-established target for the treatment of patients with non-small cell lung cancer (NSCLC). However, a large number of somatic mutations in such protein have been observed to cause drug resistance or sensitivity during pathological progression, limiting the application of reversible EGFR tyrosine kinase inhibitor therapy in NSCLC. In the current work, we describe an integration of in silico analysis and in vitro assay to profile six representative EGFR inhibitors against a panel of 71 observed somatic mutations in EGFR tyrosine kinase domain. In the procedure, the changes in interaction free energy of inhibitors with EGFR upon various mutations were calculated one by one using a rigorous computational scheme, which was preoptimized based on a set of structure-solved, affinity-known samples to improve its performance in characterizing the EGFR-inhibitor system. This method was later demonstrated to be effective in inferring drug response to the classical L858R and G719S mutations that confer constitutive activation for the EGFR kinase. It is found that the Staurosporine, a natural product isolated from the bacterium Streptomyces staurosporeus, exhibits selective inhibitory activity on the T790M and T790M/L858R mutants. This finding was subsequently solidified by in vitro kinase assay experiment; the inhibitory IC50 values of Staurosporine against wild-type, T790M and T790M/L858R mutant EGFR were measured to be 937, 12 and 3 nM, respectively.

No significant association between the XRCC3 Thr241Met polymorphism and lung cancer risk: a meta-analysis.

The development of lung cancer is significantly associated with genetic susceptibility. Findings from previous individual studies regarding the effect of X-ray repair cross-complementing group 3 Thr241Met (XRCC3 Thr241Met) polymorphism on lung cancer risk remained conflicting and inconclusive. Thus, a meta-analysis of previous relevant studies was performed to estimate this effect more precisely and to shed some light on the contradictory findings. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the correlation of XRCC3 Thr241Met polymorphism with lung cancer susceptibility. Stratified analysis according to ethnicity and sensitivity analysis was both conducted for further confirmation. Seventeen independent case-control studies involving 12,610 subjects totally were included into this meta-analysis. Overall, meta-analysis of total included studies showed that the XRCC3 Thr241Met polymorphism was not associated with risk of lung cancer in all genetic contrast models (OR Met allele vs. Thr allele = 1.01, 95 % CI 0.91-1.13, P OR = 0.810; OR Met/Met vs. Thr/Thr = 1.16, 95 % CI 0.88-1.54, P OR = 0.281; OR Thr/Met vs. Thr/Thr = 0.95, 95 % CI 0.86-1.04, P OR = 0.240; OR Met/Met + Thr/Met vs. Thr/Thr = 0.97, 95 % CI 0.89-1.06, P OR = 0.538; OR Met/Met vs. Thr/Thr + Thr/Met = 1.18, 95 % CI 0.91-1.52, P OR = 0.204). Stratified analyses in Asians and Caucasians showed similar results. Sensitivity analysis confirmed the stability and reliability of the findings. This meta-analysis of all available data did not support any appreciable association between the XRCC3 Thr241Met polymorphism and lung cancer risk in any populations.