Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC.

BACKGROUND: Osimertinib is a recommended treatment for advanced non-small-cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) mutation and as adjuvant treatment for resected EGFR-mutated NSCLC. EGFR-tyrosine kinase inhibitors have shown preliminary efficacy in unresectable stage III EGFR-mutated NSCLC. METHODS: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with unresectable EGFR-mutated stage III NSCLC without progression during or after chemoradiotherapy to receive osimertinib or placebo until disease progression occurred (as assessed by blinded independent central review) or the regimen was discontinued. The primary end point was progression-free survival as assessed by blinded independent central review. RESULTS: A total of 216 patients who had undergone chemoradiotherapy were randomly assigned to receive osimertinib (143 patients) or placebo (73 patients). Osimertinib resulted in a significant progression-free survival benefit as compared with placebo: the median progression-free survival was 39.1 months with osimertinib versus 5.6 months with placebo, with a hazard ratio for disease progression or death of 0.16 (95% confidence interval [CI], 0.10 to 0.24; P<0.001). The percentage of patients who were alive and progression free at 12 months was 74% (95% CI, 65 to 80) with osimertinib and 22% (95% CI, 13 to 32) with placebo. Interim overall survival data (maturity, 20%) showed 36-month overall survival among 84% of patients with osimertinib (95% CI, 75 to 89) and 74% with placebo (95% CI, 57 to 85), with a hazard ratio for death of 0.81 (95% CI, 0.42 to 1.56; P = 0.53). The incidence of adverse events of grade 3 or higher was 35% in the osimertinib group and 12% in the placebo group; radiation pneumonitis (majority grade, 1 to 2) was reported in 48% and 38%, respectively. No new safety concerns emerged. CONCLUSIONS: Treatment with osimertinib resulted in significantly longer progression-free survival than placebo in patients with unresectable stage III EGFR-mutated NSCLC. (Funded by AstraZeneca; LAURA ClinicalTrials.gov number, NCT03521154.).

Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Non-Squamous EGFR-Wildtype NSCLC in the Phase 2 LUMINOSITY Trial.

PURPOSE: Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase 2 LUMINOSITY trial (NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage 1) and expand the selected group for efficacy evaluation (stage 2). Stage 2 enrolled patients with non-squamous epidermal growth factor receptor (EGFR)-wildtype NSCLC. METHODS: Eligible patients had locally advanced/metastatic c-Met protein-overexpressing NSCLC and ≤2 prior lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in non-squamous EGFR-wildtype NSCLC was defined as ≥25% tumor cells with 3+ staining (high [≥50% 3+]; intermediate [≥25%-<50%]). Teliso-V was administered at 1.9 mg/kg every 2 weeks. Primary endpoint was overall response rate (ORR) by independent central review. RESULTS: In total, 172 patients with non-squamous EGFR-wildtype NSCLC received Teliso-V in stages 1 and 2. ORR was 28.6% (95% CI, 21.7-36.2; c-Met high, 34.6% [24.2-46.2]; c-Met intermediate, 22.9% [14.4-33.4]). Median duration of response was 8.3 months (95% CI, 5.6-11.3; c-Met high, 9.0 [4.2-13.0]; c-Met intermediate: 7.2 [5.3-11.5]). Median overall survival was 14.5 months (95% CI, 9.9-16.6; c-Met high, 14.6 [9.2-25.6]; c-Met intermediate, 14.2 [9.6-16.6]). Median progression-free survival was 5.7 months (95% CI, 4.6-6.9; c-Met high, 5.5 [4.1-8.3]; c-Met intermediate: 6.0 [4.5-8.1]). Most common any-grade treatment-related adverse events (AEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%); the most common grade ≥3 was peripheral sensory neuropathy (7%). CONCLUSION: Teliso-V was associated with durable responses in c-Met protein-overexpressing non-squamous EGFR-wildtype NSCLC, especially in those with high c-Met. AEs were generally manageable.

Observation of 2D-magnesium-intercalated gallium nitride superlattices.

Since the demonstration of p-type gallium nitride (GaN) through doping with substitutional magnesium (Mg) atoms1,2, rapid and comprehensive developments, such as blue light-emitting diodes, have considerably shaped our modern lives and contributed to a more carbon-neutral society3-5. However, the details of the interplay between GaN and Mg have remained largely unknown6-11. Here we observe that Mg-intercalated GaN superlattices can form spontaneously by annealing a metallic Mg film on GaN at atmospheric pressure. To our knowledge, this marks the first instance of a two-dimensional metal intercalated into a bulk semiconductor, with each Mg monolayer being intricately inserted between several monolayers of hexagonal GaN. Characterized as an interstitial intercalation, this process induces substantial uniaxial compressive strain perpendicular to the interstitial layers. Consequently, the GaN layers in the Mg-intercalated GaN superlattices exhibit an exceptional elastic strain exceeding -10% (equivalent to a stress of more than 20 GPa), among the highest recorded for thin-film materials12. The strain alters the electronic band structure and greatly enhances hole transport along the compression direction. Furthermore, the Mg sheets induce a unique periodic transition in GaN polarity, generating polarization-field-induced net charges. These characteristics offer fresh insights into semiconductor doping and conductivity enhancement, as well as into elastic strain engineering of nanomaterials and metal-semiconductor superlattices13.

USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer.

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.

D3S-001, a KRAS G12C inhibitor with rapid target engagement kinetics, overcomes nucleotide cycling and demonstrates robust preclinical and clinical activities.

First-generation KRAS G12C inhibitors, such as sotorasib and adagrasib, are limited by the depth and duration of clinical responses. One potential explanation for their modest clinical activity is the dynamic "cycling" of KRAS between its GDP- and GTP-bound states, raising controversy about whether targeting the GDP-bound form can fully block this oncogenic driver. We herein report D3S-001, a next generation GDP-bound G12C inhibitor with faster target engagement (TE) kinetics, depletes cellular active KRAS G12C at nanomolar concentrations. In the presence of growth factors, such as EGF and HGF, the ability of sotorasib and adagrasib to inhibit KRAS was compromised whereas the TE kinetics of D3S-001 was nearly unaffected, a unique feature differentiating D3S-001 from other GDP-bound G12C inhibitors. Furthermore, the high covalent potency and cellular TE efficiency of D3S-001 contributed to robust anti-tumor activity preclinically and translated into promising clinical activity in an ongoing phase 1 trial (NCT05410145).

IMpower210: A phase III study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer.

Objective: IMpower210 (NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs. docetaxel as second-line treatment for advanced non-small cell lung cancer (NSCLC) in East Asian patients. Methods: Key eligibility criteria for this phase III, open-label, randomized study included age ≥18 years; histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system (7th edition); Eastern Cooperative Oncology Group performance status of 0 or 1; and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab (1,200 mg) or docetaxel (75 mg/m2). The primary study endpoint was overall survival (OS) in the intention-to-treat (ITT) population with wild-type epidermal growth factor receptor expression (ITT EGFR-WT) and in the overall ITT population. Results: Median OS in the ITT EGFR-WT population (n=467) was 12.3 [95% confidence interval (95% CI), 10.3-13.8] months in the atezolizumab arm (n=312) and 9.9 (95% CI, 7.8-13.9) months in the docetaxel arm [n=155; stratified hazard ratio (HR), 0.82; 95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5 (95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1 (95% CI, 8.4-14.2) months (n=377) with docetaxel treatment (n=188; stratified HR, 0.87; 95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm. Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade 3/4 TRAEs.

Dysregulation of peripheral and intratumoral KLRG1+ CD8+T cells is associated with immune evasion in patients with non-small-cell lung cancer.

OBJECTIVES: Killer cell lectin like receptor G1 (KLRG1) is identified as a co-inhibitory receptor for NK cells and antigen-experienced T cells. The role of KLRG1 in immune regulation in patients with non-small cell lung cancer (NSCLC) remains poorly understood. MATERIALS AND METHODS: We measured the proportion and immune function of KLRG1+CD8+T cells derived from peripheral blood in patients with NSCLC by flow cytometry. Besides, using data from the gene expression profiles and single-cell sequencing, we explored the expression and immune role of KLRG1 in tumor tissues of patients with NSCLC. We further determined the prognostic value of KLRG1 in terms of overall survival (OS) in NSCLC patients. RESULTS: We found that the proportion of KLRG1+CD8+T cells in peripheral blood significantly increased in patients with NSCLC as compared to those with benign pulmonary nodules and healthy donors. Peripheral KLRG1+CD8+T cell proportion was increased in elder subjects compared to that in younger ones, implying an immunosenescence phenotype. Moreover, the KLRG1+CD8+T cell levels were positively correlated with tumor size and TNM stage in the NSCLC cohort. In vitro stimulation experiments demonstrated that the KLRG1+CD8+T cells from peripheral blood expressed higher levels of Granzyme B and perforin than the KLRG1-CD8+ T cells. However, single-cell RNA sequencing data revealed that the KLRG1+CD8+ T cells were less infiltrated in tumor microenvironment and exhibited impaired cytotoxicity. The KLRG1 gene expression levels were significantly lower in tumor tissues than that in normal lung tissues, and were inversely correlated with CDH1 expression levels. Moreover, higher expression of CDH1 in tumor tissues predicted worse overall survival only in patients with KLRG1-high expression, but not in the KLRG1-low subset. CONCLUSION: This study demonstrates that KLRG1+CD8+T cells were associated with tumor immune evasion in NSCLC and suggests KLRG1 as a potential immunotherapy target.

A large-scale, multicenter characterization of BRAF G469V/A-mutant non-small cell lung cancer.

BACKGROUND: Mutated BRAF is identified in 1%-5% non-small cell lung cancer (NSCLC) patients, with non-V600 mutations accounting for 50%-70% of these. The most common non-V600 mutation is BRAF G469V/A. Currently, there are no targeted therapies available for non-V600 mutated patients. A recent report provided interesting preclinical evidence revealing sensitivity of BRAF G469V to epidermal growth factor receptor (EGFR) inhibitors, raising the possibility of repurposing anti-EGFR agents. It is therefore worthy to characterize the clinical and molecular features of BRAF G469V/A-mutant NSCLC to provide more insights for precision therapy. METHODS: We conducted a retrospective screening of 25,694 Chinese patients with advanced or metastatic NSCLC to identify individuals with mutated BRAF. Additionally, we performed similar screenings on patients with adenocarcinoma (LUAD) from The Cancer Genome Atlas (TCGA) cohort (n = 567) and the MSKCC cohort (n = 1152). Subsequently, we characterized the clinical and molecular features of the patients carrying BRAF mutations. RESULTS: BRAF G469V was identified in 28 (0.1%) patients from the Chinese NSCLC cohort and 5 (0.9%) from TCGA-LUAD. Notably, none was identified in the MSKCC cohort. G469A was found in 79 (0.3%) Chinese patients, 2 (0.4%) from TCGA-LUAD, and 9 (0.8%) from the MSKCC cohort. Relative allele frequency analysis suggested most BRAF mutations as driven clones. Tumor mutation burden (median 4 mutations/Mb) was not significantly different between patients carrying G469V, G469A, V600E, or other BRAF mutations. Surprisingly, KRAS mutations were found in approximately 50% of patients with G469V mutation and about 8% of patients with G469A mutation, representing a prominent potential resistance mechanism against EGFR inhibitors. Structural modeling suggested BRAF G469V and G469A as binding partners of gefitinib. CONCLUSION: Our large-scale analysis characterized the prevalence and mutational landscape of BRAF G469V/A-mutant NSCLC and proposed gefitinib as a potential option, providing a basis for further investigations on treating BRAF-mutated NSCLC.

EGFR-mutant NSCLC may remodel TME from non-inflamed to inflamed through acquiring resistance to EGFR-TKI treatment.

BACKGROUND: EGFR-TKI represent the standard first-line therapy for advanced NSCLC harboring EGFR mutations. However, resistance to EGFR-TKI inevitably develops in nearly all patients. Previous clinical study have demonstrated that, some patients that failed EGFR-TKI therapy show a benefit outcome from immunotherapy. Our objective is to explore the immune microenviroment remodeling induced by EGFR-TKI treatment in EGFR mutant lung cancer patients and to investigate the immune cell types and potential molecular signatures involved. METHODS: A cohort of 37 EGFR mutant advanced-stage NSCLC patients, who are resistant to at least one type of TKI treatment, was retrospectively established. Both pre-treatment and TKI resistance tumor FFPE samples of each pairs were collected. Transcriptional profiling and bioinformatics analysis were employed to evaluate the change of immune associated hallmarks before and after EGFR-TKI therapy. RESULTS: Tumor samples after EGFR-TKI treatment displayed enrichment of proinflammatory signaling like interferon-γ, allograft rejection and inflammatory response. Of note, cytotoxic factor granzyme A as well as PD-L1 were found to be more expressed in EGFR-TKI resistance samples. Approximately 33.3 % (11/33) of EGFR-TKI treated samples were classified as "hot" tumor, especially for EGFR L858R mutated NSCLC patients (46.7 %,7/15). Effector cells were significantly overexpressed in 'hot' tumors feature following TKI resistance. In addition, we found that four effector genes (CD8A, CDB8, GZMB, GZMK) showed higher expression in 'hot' tumors post-TKI resistance, and its 4-gene effector cell signature was found to have a good correlation with survival benefit in external immunotherapy database. CONCLUSIONS: TKI treatment may initiate immune activation in EGFR mutant NSCLC, leading to changes in immune cell infiltration following TKI resistance. We mechanistically explored that this might be due to an increased immune response caused by the rise in effector cells post-TKI resistance.

Perioperative Nivolumab in Resectable Lung Cancer.

BACKGROUND: Standard treatment with neoadjuvant nivolumab plus chemotherapy significantly improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative treatment (i.e., neoadjuvant therapy followed by surgery and adjuvant therapy) with nivolumab may further improve clinical outcomes. METHODS: In this phase 3, randomized, double-blind trial, we assigned adults with resectable stage IIA to IIIB NSCLC to receive neoadjuvant nivolumab plus chemotherapy or neoadjuvant chemotherapy plus placebo every 3 weeks for 4 cycles, followed by surgery and adjuvant nivolumab or placebo every 4 weeks for 1 year. The primary outcome was event-free survival according to blinded independent review. Secondary outcomes were pathological complete response and major pathological response according to blinded independent review, overall survival, and safety. RESULTS: At this prespecified interim analysis (median follow-up, 25.4 months), the percentage of patients with 18-month event-free survival was 70.2% in the nivolumab group and 50.0% in the chemotherapy group (hazard ratio for disease progression or recurrence, abandoned surgery, or death, 0.58; 97.36% confidence interval [CI], 0.42 to 0.81; P<0.001). A pathological complete response occurred in 25.3% of the patients in the nivolumab group and in 4.7% of those in the chemotherapy group (odds ratio, 6.64; 95% CI, 3.40 to 12.97); a major pathological response occurred in 35.4% and 12.1%, respectively (odds ratio, 4.01; 95% CI, 2.48 to 6.49). Grade 3 or 4 treatment-related adverse events occurred in 32.5% of the patients in the nivolumab group and in 25.2% of those in the chemotherapy group. CONCLUSIONS: Perioperative treatment with nivolumab resulted in significantly longer event-free survival than chemotherapy in patients with resectable NSCLC. No new safety signals were observed. (Funded by Bristol Myers Squibb; CheckMate 77T ClinicalTrials.gov number, NCT04025879.).

Single-Walled Carbon Nanotube-Reinforced PEDOT: PSS Hybrid Electrodes for High-Performance Ionic Electroactive Polymer Actuator.

Ionic electroactive polymer (iEAP) actuators are recognized as exceptional candidates for artificial muscle development, with significant potential applications in bionic robotics, space exploration, and biomedical fields. Here, we developed a new iEAP actuator utilizing high-purity single-walled carbon nanotubes (SWCNTs)-reinforced poly(3, 4-ethylenedioxythiophene)/poly(4-styrenesulfonate) (PEDOT: PSS, PP) hybrid electrodes and a Nafion/EMIBF4 ion-exchange membrane via a straightforward and efficient spray printing technique. The SWCNT/PP actuator exhibits significantly enhanced electric conductivity (262.9 S/cm) and specific capacitance (22.5 mF/cm2), benefitting from the synergistic effect between SWCNTs and PP. These improvements far surpass those observed in activated carbon aerogel bucky-gel-electrode-based actuators. Furthermore, we evaluated the electroactive behaviors of the SWCNT/PP actuator under alternating square-wave voltages (1-3 V) and frequencies (0.01-100 Hz). The results reveal a substantial bending displacement of 6.44 mm and a high bending strain of 0.61% (at 3 V, 0.1 Hz), along with a long operating stability of up to 10,000 cycles (at 2 V, 1 Hz). This study introduces a straightforward and efficient spray printing technique for the successful preparation of iEAP actuators with superior electrochemical and electromechanical properties as intended, which hold promise as artificial muscles in the field of bionic robotics.

Neoadjuvant low-dose radiotherapy plus durvalumab and chemotherapy for potentially resectable stage III NSCLC: A phase Ib dose-escalation study.

BACKGROUND AND PURPOSE: This phase Ib study was designed to assess the safety/tolerability and preliminary antitumor activity of neoadjuvant low-dose radiotherapy (LDRT) plus durvalumab and chemotherapy for potentially resectable stage III non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Eligible patients received dose-escalated radiotherapy (10 Gy in 5 fractions [cohort 1], 20 Gy in 10 fractions [cohort 2], and 30 Gy in 15 fractions [cohort 3]) according to a 3 + 3 design, with concurrent durvalumab plus standard chemotherapy for two cycles. Primary objective was safety/tolerability. Secondary objectives included major pathological response (MPR), pathological complete response (pCR), event-free survival (EFS), and exploratory biomarker analysis. RESULTS: Nine patients were enrolled and completed the planned neoadjuvant therapy. No dose-limiting toxicity was recorded. Grade 3-4 treatment-related adverse events were observed in three (33.3 %) patients. Seven (77.8 %) patients successfully converted to resectable cases with R0 resection. No treatment-related surgical delay or death was reported. The MPR and pCR rates were both 33.3 % % (1/3) for cohort 1, 66.7 % (2/3) and 0.0 % for cohort 2, and 100.0 % (3/3), and 66.7 % (2/3) for cohort 3. At data cutoff, the 12 month-EFS rates were 33.3 %, 66.7 %, and 100 % for three cohorts, respectively. By biomarker analysis, TMB values were higher in either pathologically or radiologically responders than in others (all p > 0.05). CONCLUSION: Neoadjuvant LDRT plus durvalumab and chemotherapy was well-tolerated in potentially resectable stage III NSCLC. The preliminary efficacy supports this combined regimen's potential, the optimal radiotherapy dosage was determined to be 30 Gy in 15 fractions, warranting further clinical investigation.

Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer.

BACKGROUND: Platinum-based chemotherapy is the recommended adjuvant treatment for patients with resectable, ALK-positive non-small-cell lung cancer (NSCLC). Data on the efficacy and safety of adjuvant alectinib as compared with chemotherapy in patients with resected ALK-positive NSCLC are lacking. METHODS: We conducted a global, phase 3, open-label, randomized trial in which patients with completely resected, ALK-positive NSCLC of stage IB (tumors ≥4 cm), II, or IIIA (as classified according to the seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer and Union for International Cancer Control) were randomly assigned in a 1:1 ratio to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy in four 21-day cycles. The primary end point was disease-free survival, tested hierarchically among patients with stage II or IIIA disease and then in the intention-to-treat population. Other end points included central nervous system (CNS) disease-free survival, overall survival, and safety. RESULTS: In total, 257 patients were randomly assigned to receive alectinib (130 patients) or chemotherapy (127 patients). The percentage of patients alive and disease-free at 2 years was 93.8% in the alectinib group and 63.0% in the chemotherapy group among patients with stage II or IIIA disease (hazard ratio for disease recurrence or death, 0.24; 95% confidence interval [CI], 0.13 to 0.45; P<0.001) and 93.6% and 63.7%, respectively, in the intention-to-treat population (hazard ratio, 0.24; 95% CI, 0.13 to 0.43; P<0.001). Alectinib was associated with a clinically meaningful benefit with respect to CNS disease-free survival as compared with chemotherapy (hazard ratio for CNS disease recurrence or death, 0.22; 95% CI, 0.08 to 0.58). Data for overall survival were immature. No unexpected safety findings were observed. CONCLUSIONS: Among patients with resected ALK-positive NSCLC of stage IB, II, or IIIA, adjuvant alectinib significantly improved disease-free survival as compared with platinum-based chemotherapy. (Funded by F. Hoffmann-La Roche; ALINA ClinicalTrials.gov number, NCT03456076.).

Benzene-Linked Polymeric Carbon Nitride for Enhanced Photocatalytic Hydrogen Production.

Cross-linking with functional molecular species in polymeric carbon nitride (PCN) could offer a positive strategy that tunes its molecular structure with excellent conductivity to improve photocatalytic activity. Herein, the benzene ring-cross-linked photocatalyst is obtained via the polymerization of urea, melamine, and trimesic acid. Benzene ring-cross-linked PCN narrows the band gap and augments the push-pull effect of carriers, thus enhancing visible light harvesting and transfer easiness of photogenerated electron/hole pairs. Notably, the amount of trimesic acid was optimized during the benzene ring-cross-linked photocatalyst preparation (marked as 01T/A-CN, 02T/A-CN, and 03T/A-CN). Among them, 02T/A-CN photocatalyst achieved an excellent hydrogen production rate of 1931 µmol/h·g, which is higher than that of CN under visible light and beyond most reported. Theoretical calculations further confirmed that the introduction of benzene ring significantly reduces the band gap of PCN, bringing the delocalized electron, a longer intramolecular electron transition distance, and molecular bending. All those factors made benzene ring-cross-linked PCN with improved photocatalytic hydrogen production under visible light irradiation.

Summary of Research: Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.

This is a summary of the original article ?Overall survival with osimertinib in resected EGFR-mutated NSCLC.Ë® Osimertinib blocks the activity of the epidermal growth factor receptor (EGFR) on cancer cells, causing cancer cell death and tumor shrinkage, and is an effective treatment for EGFR-mutated non-small cell lung cancer (NSCLC). The ADAURA study assessed the effects of osimertinib versus placebo in patients with EGFR-mutated (exon 19 deletion or L858R) early stage (IB-IIIA) NSCLC removed by surgery (resected). Previous results from ADAURA demonstrated that patients treated with osimertinib stayed alive and cancer-free (disease-free survival) significantly longer than patients who received placebo. Recent data showed the overall length of time patients were alive after starting treatment (overall survival). In both the primary stage II-IIIA and overall stage IB-IIIA populations, patients in the osimertinib group had a significant 51% reduction in the risk of death compared with the placebo group. The data demonstrated that osimertinib after surgery significantly improved overall survival in patients with resected, EGFR-mutated, stage IB-IIIA NSCLC.

Photocatalytic Degradation of Tetracycline Hydrochloride Based on the Structure-Property Exploration of BiOCl.

The correlation between structure and properties in the photodegradation reaction of bismuth oxychloride (BiOCl) was explored in this work. Three BiOCl samples with different sizes, morphological structures, and defects were prepared through a hydrothermal method with experimental manipulation. Their structural properties were comprehensively characterized using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, electron spin resonance, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, ultraviolet-visible diffuse reflectance spectroscopy, and photoluminescence. Taking the photodegradation of tetracycline hydrochloride (TC-HCl) as the probe reaction, we found that high activity could be achieved by decreasing their crystal size and thickness, introducing proper defects in the structure, and assembling the nanosheets to get microball structure. Combined with radical-scavenge experiments and electron spin resonance (ESR) spin-trap spectra, we conclude that ̇O2- was the dominant reactive oxygen species for the degradation reaction. The degradation detailed pathway of TC-HCl was further analyzed using liquid chromatography-mass spectrometry. This work explores the structure-property correlation of BiOCl and provides strategies for the rational design of active photocatalysts for water remediation.

Nitrogen-doped biomass-derived carbon dots for fluorescence determination of sunset yellow.

Sunset Yellow (SY) is a widely used food coloring in the food industry. However, exceeding the allowable limit of this dye poses a significant threat to human health. To address this issue, we developed Lycium ruthenicum-derived nitrogen-doped carbon dots (N-CDs) with a stable blue fluorescence through hydrothermal treatment for SY determination. The quantum yield (QY) of these N-CDs was found to be up to 10.63%. Physical characterization of N-CDs was performed using various spectroscopic techniques to confirm their excellent photostability and non-toxic properties. Furthermore, the presence of SY had a substantial quenching effect on the fluorescence intensity (F0/F) of the N-CDs. Leveraging this observation, we developed a fluorescent sensor for the determination of SY in the concentration range of 0.05 to 35.0 µM, with a limit of detection (LOD, 3σ/K) of 17 nM. The excellent fluorescent sensor also showed satisfactory results in the practical drink samples. Moreover, the stability and cytotoxicity of N-CDs as a fluorescent probe were studied. Finally, the N-CDs were applied to cell imaging using A549 cells.

Long-term prognosis analysis of surgical therapy for bilateral synchronous multiple primary lung cancer: a follow-up of 293 cases.

Background: Bilateral synchronous multiple primary lung cancer (BSMPLC) presents significant clinical challenges due to its unique characteristics and prognosis. Understanding the risk factors that influence overall survival (OS) and recurrence-free survival (RFS) is crucial for optimizing therapeutic strategies for BSMPLC patients. Methods: We retrospectively analyzed clinical characteristics and treatment outcomes of 293 patients with BSMPLC who underwent surgical treatment between January 2010 and July 2017. Results: The 10-year OS and RFS rates were 96.1% and 92.8%, respectively. Preoperative forced expiratory volume in 1 second (FEV1) ≥70% [hazard ratio (HR), 0.214; 95% confidence interval (CI): 0.053 to 0.857], identical pathology types (HR, 9.726; 95% CI: 1.886 to 50.151), largest pT1 (HR, 7.123; 95% CI: 2.663 to 19.055), and absence of lymphovascular invasion (LVI; HR, 7.021; 95% CI: 1.448 to 34.032) emerged as independent predictors of improved OS. Moreover, the sum of tumor sizes less than or equal to 3 cm (HR, 6.229; 95% CI: 1.411 to 27.502) and absence of pleural invasion (HR, 3.442; 95% CI: 1.352 to 8.759) were identified as independent predictors of enhanced RFS. The presence or absence of residual nodules after bilateral surgery did not influence patients' OS (P=0.987) and RFS (P=0.054). Conclusions: Patients with BSMPLC who underwent surgery generally had a favorable prognosis. Whether or not to remove all nodules bilaterally does not affect the patient's long-term prognosis, suggesting the need for an individualized surgical approach.

Remodeling of the Intra-Conduit Inflammatory Microenvironment to Improve Peripheral Nerve Regeneration with a Neuromechanical Matching Protein-Based Conduit.

Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra-conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory-polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein-based conduits. Moreover, the NGC can gradually regulate the intra-conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments.

Biomass-derived carbon dots as emerging visual platforms for fluorescent sensing.

Biomass-derived carbon dots (CDs) are non-toxic and fluorescently stable, making them suitable for extensive application in fluorescence sensing. The use of cheap and renewable materials not only improves the utilization rate of waste resources, but it is also drawing increasing attention to and interest in the production of biomass-derived CDs. Visual fluorescence detection based on CDs is the focus of current research. This method offers high sensitivity and accuracy and can be used for rapid and accurate determination under complex conditions. This paper describes the biomass precursors of CDs, including plants, animal remains and microorganisms. The factors affecting the use of CDs as fluorescent probes are also discussed, and a brief overview of enhancements made to the preparation process of CDs is provided. In addition, the application prospects and challenges related to biomass-derived CDs are demonstrated.