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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.
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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.).
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Compostos de Platina , Humanos , Carbazóis/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Piperidinas/uso terapêutico , Receptores Proteína Tirosina Quinases , Resultado do Tratamento , Administração Oral , Administração Intravenosa , Compostos de Platina/uso terapêutico , Antineoplásicos/uso terapêuticoRESUMO
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.).
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Acrilamidas , Compostos de Anilina , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acrilamidas/uso terapêutico , Acrilamidas/efeitos adversos , Compostos de Anilina/uso terapêutico , Compostos de Anilina/efeitos adversos , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Método Duplo-Cego , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Indóis , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Mutação , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Pirimidinas , /uso terapêuticoRESUMO
BACKGROUND: The early-generation ROS1 tyrosine kinase inhibitors (TKIs) that are approved for the treatment of ROS1 fusion-positive non-small-cell lung cancer (NSCLC) have antitumor activity, but resistance develops in tumors, and intracranial activity is suboptimal. Repotrectinib is a next-generation ROS1 TKI with preclinical activity against ROS1 fusion-positive cancers, including those with resistance mutations such as ROS1 G2032R. METHODS: In this registrational phase 1-2 trial, we assessed the efficacy and safety of repotrectinib in patients with advanced solid tumors, including ROS1 fusion-positive NSCLC. The primary efficacy end point in the phase 2 trial was confirmed objective response; efficacy analyses included patients from phase 1 and phase 2. Duration of response, progression-free survival, and safety were secondary end points in phase 2. RESULTS: On the basis of results from the phase 1 trial, the recommended phase 2 dose of repotrectinib was 160 mg daily for 14 days, followed by 160 mg twice daily. Response occurred in 56 of the 71 patients (79%; 95% confidence interval [CI], 68 to 88) with ROS1 fusion-positive NSCLC who had not previously received a ROS1 TKI; the median duration of response was 34.1 months (95% CI, 25.6 to could not be estimated), and median progression-free survival was 35.7 months (95% CI, 27.4 to could not be estimated). Response occurred in 21 of the 56 patients (38%; 95% CI, 25 to 52) with ROS1 fusion-positive NSCLC who had previously received one ROS1 TKI and had never received chemotherapy; the median duration of response was 14.8 months (95% CI, 7.6 to could not be estimated), and median progression-free survival was 9.0 months (95% CI, 6.8 to 19.6). Ten of the 17 patients (59%; 95% CI, 33 to 82) with the ROS1 G2032R mutation had a response. A total of 426 patients received the phase 2 dose; the most common treatment-related adverse events were dizziness (in 58% of the patients), dysgeusia (in 50%), and paresthesia (in 30%), and 3% discontinued repotrectinib owing to treatment-related adverse events. CONCLUSIONS: Repotrectinib had durable clinical activity in patients with ROS1 fusion-positive NSCLC, regardless of whether they had previously received a ROS1 TKI. Adverse events were mainly of low grade and compatible with long-term administration. (Funded by Turning Point Therapeutics, a wholly owned subsidiary of Bristol Myers Squibb; TRIDENT-1 ClinicalTrials.gov number, NCT03093116.).
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Proteínas Tirosina Quinases , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , Antineoplásicos/uso terapêutico , Resultado do TratamentoRESUMO
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.).
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia Neoadjuvante , Nivolumabe , Humanos , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Nivolumabe/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Idoso , Método Duplo-Cego , Quimioterapia Adjuvante , Intervalo Livre de Progressão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Estadiamento de Neoplasias , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , PneumonectomiaRESUMO
BACKGROUND: Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). METHODS: In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. RESULTS: Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. CONCLUSIONS: Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).
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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.
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Linfócitos do Interstício Tumoral , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: Non-small cell lung cancer (NSCLC) patients with EGFR mutations exhibit an unfavorable response to immune checkpoint inhibitor (ICI) monotherapy, and their tumor microenvironment (TME) is usually immunosuppressed. TGF-ß plays an important role in immunosuppression; however, the effects of TGF-ß on the TME and the efficacy of anti-PD-1 immunotherapy against EGFR-mutated tumors remain unclear. METHODS: Corresponding in vitro studies used the TCGA database, clinical specimens, and self-constructed mouse cell lines with EGFR mutations. We utilized C57BL/6N and humanized M-NSG mouse models bearing EGFR-mutated NSCLC to investigate the effects of TGF-ß on the TME and the combined efficacy of TGF-ß blockade and anti-PD-1 therapy. The changes in immune cells were monitored by flow cytometry. The correlation between TGF-ß and immunotherapy outcomes of EGFR-mutated NSCLC was verified by clinical samples. RESULTS: We identified that TGF-ß was upregulated in EGFR-mutated NSCLC by EGFR activation and subsequent ERK1/2-p90RSK phosphorylation. TGF-ß directly inhibited CD8+ T cell infiltration, proliferation, and cytotoxicity both in vitro and in vivo, but blocking TGF-ß did not suppress the growth of EGFR-mutated tumors in vivo. Anti-TGF-ß antibody combined with anti-PD-1 antibody significantly inhibited the proliferation of recombinant EGFR-mutated tumors in C57BL/6N mice, which was superior to their monotherapy. Mechanistically, the combination of anti-TGF-ß and anti-PD-1 antibodies significantly increased the infiltration of CD8+ T cells and enhanced the anti-tumor function of CD8+ T cells. Moreover, we found that the expression of TGF-ß1 in EGFR-TKI resistant cell lines was significantly higher than that in parental cell lines. The combination of anti-TGF-ß and nivolumab significantly inhibited the proliferation of EGFR-TKI resistant tumors in humanized M-NSG mice and prolonged their survival. CONCLUSIONS: Our results reveal that TGF-ß expression is upregulated in NSCLC with EGFR mutations through the EGFR-ERK1/2-p90RSK signaling pathway. High TGF-ß expression inhibits the infiltration and anti-tumor function of CD8+ T cells, contributing to the "cold" TME of EGFR-mutated tumors. Blocking TGF-ß can reshape the TME and enhance the therapeutic efficacy of anti-PD-1 in EGFR-mutated tumors, which provides a potential combination immunotherapy strategy for advanced NSCLC patients with EGFR mutations.
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Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Neoplasias Pulmonares , Mutação , Receptor de Morte Celular Programada 1 , Fator de Crescimento Transformador beta , Animais , Feminino , Humanos , Masculino , Camundongos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/metabolismo , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Mutação/genética , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral/efeitos dos fármacosRESUMO
The refractive index (RI) measurment of the liquid often changes with the sensor's temperature. Accurate RI measurements require simultaneous measurements of the liquid temperature to calibrate the RI measurement. This study proposed what we believe to be a novel dual D-shaped plastic optical fiber sensor capable of simultaneously measuring both RI and temperature. A fluorescent material made of rhodamine B (RhB) is embedded in one of the D-shaped structures of the dual D-shaped fiber, which can be excited by a green laser to produce orange fluorescence. The fluorescence and the input laser of the fiber are superimposed at the output end of the fiber to form a specklegram containing information of two wavelengths. It was found through experiments that the effects of temperature and RI change on the red and green channels of the specklegrams are different, and the neural network can learn this feature to complete the measurement of both RI and temperature parameters. For RI sensing, the maximum error between the average predicted value and the true value of the test set is 0.0005. For temperature sensing, the maximum error between the average predicted value and the true value of the test set is 0.26°C. In addition, because the intensity change of the fluorescence varies linearly with RI and temperature, the sensor also has good stability.
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Molecular doping is an innovative approach to modify the electronic configuration of carbon nitride (CN) photocatalysts, enhancing visible light absorption and optimizing the recombination of electron-hole pairs in photocatalytic H2 generation. Unlike the conventional heteroatom incorporation strategy, molecular doping offers a more effective means of structure optimization and conjugated framework. This Perspective studies recent advancements in benzene-ring doping for CN, emphasizing the correlation between structure and photocatalytic activity. The advantages and disadvantages of molecular doping in CN are thoroughly demonstrated, underscoring the importance of utilizing molecular doping to fine-tune both electronic and physical structures for enhanced photocatalytic efficacy. Insights are provided on strategies to address limitations and explore new prospects in the field of molecular doping methodologies.
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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 ÌO2- 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.
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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.
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Various efficient strategies have been developed to overcome the anodic electrocatalyst issue of methanol-based fuel cells owing to their complicated methanol electrooxidation mechanism. In this work, PtCo nanoparticles with adjustable compositions supported on multiwalled carbon nanotubes (Pt1Cox/MWCNTs) through the adsorbing-coating-annealing-etching route were synthesized. Compared with the Pt/C catalyst, Pt1Co3/MWCNTs exhibit better electrocatalytic MOR activity in both activity and durability. Notably, the electrochemical mass and specific activity of the as-prepared catalyst are 1.04 mA µg-1Pt and 2.18 mA cm-2, respectively, which are higher than those of the Pt/C catalyst. Moreover, the as-prepared sample revealed lower onset potential during the CO stripping test. Furthermore, the Pt1Co3/MWCNTs possess a lower current density decrease rate in chronoamperometry and cyclic durability tests. The enhancement of activity and stability of Pt1Co3/MWCNTs could be ascribed to their ordered morphological structure, the electronic interaction between MWCNTs and PtCo nanoparticles, and the suitable electronic structure effect between Pt/Co ratios. The concept of the catalyst design in this study offers a different guideline for constructing the novel methanol electrooxidation catalyst, which will accelerate the widespread fuel cell practical application.
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Monitoring levels of excessive aluminum ions (Al3+) is crucial as it can harm the immune system, reduce enzyme activity, cause cell death, and damage environmental and biological systems. Developing a fast and efficient Al3+ ion determination method is the key to addressing this issue. In this work, red-emitting fluorescent copper nanoclusters (CuNCs) were synthesized using N-acetyl-l-cysteine (NAC) as a ligand and CuCl2·2H2O through a facile procedure. The NAC-CuNCs exhibited a large Stokes shift and displayed remarkable luminescence properties. A method for detecting Al3+ through a fluorescence probe was proposed. Its fluorescence mechanism was also explored. The probe showed rapid responsiveness (within 1 min) to Al3+ ion determination. The detection limit for Al3+ was found to be 19.7 nM, which is significantly lower than the WHO's value and most reports, with a linear range of 0-52.9 µM. The determination of Al3+ concentrations in actual water using the fluorescence probe yielded satisfactory outcomes. Moreover, the visual detection of Al3+ ions was also achieved through a smartphone, which can enhance its fast and practical detection.
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Piezo-photocatalytic efficiency is severely constrained by the wide band gap and bad piezoelectric properties. Herein, La(Mn0.5Ni0.5)O3 was successfully introduced into NaNbO3 lattices (referred to as 0LMN, 0.05LMN, 0.10LMN, and 0.15LMN) through a water-based sol-gel method. The piezo-photocatalytic degradation ratio for Rhodamine B (RhB) is enhanced from 59.7% (0LMN) to 89.7% (0.10LMN) within 100 min, and the kinetic rate constant (k) is increased from 0.009 to 0.022 min-1. The enhanced performance is attributed to (i) the narrowed band gap (from 3.40 to 2.84 eV), which is conducive to the generation of photogenerated electrons and holes, and (ii) the enhanced piezoelectric properties, which can strengthen the piezoelectric polarization, thereby accelerating the separation of the photogenerated electrons and holes. And we also found that the synergetic effect of photocatalysis and piezocatalysis was superior to that of photocatalysis and piezocatalysis alone. This study could provide new perspectives for the reasonable construction of an efficient catalyst in the piezo-photocatalytic field.
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Electrochemical sensing (ES) is crucial for improving data acquisition in wastewater treatment, but obtaining the signal for a low electroactive analyte is challenging. Here, we propose an electrochemical acid-base transport limitation (eABTL) principle for inertness-based sensing, offering a new insight into generating ES signals from an interfacial transport process rather than electron transfer. This principle enables potential ES application for various weak acids and bases (WABs) without reactions themselves. We established an eABTLP method for detecting orthophosphate in solutions as a proof of concept, demonstrating commendable accuracy and precision, and a wide detection range from 10 µM to over 300 mM. Endogenous interferences were identified using 23 weak acids, indicating no significant endogenous interfering factors in typical wastewaters. Of them, volatile fatty acids are the main interference, but their effect can be eliminated by adjusting pH above 6.0. Exogenous factors like anions, cations, ion strength, temperature, organic load, and dissolved oxygen were examined, and most of their effects can be ignored by maintaining consistent analytical procedures between calibration curve and sample. Furthermore, measurement of wastewater samples confirmed the applicability toward domestic wastewater and demonstrated its wide applicability when combined with digestion pretreatment. Given the merits of inertness-based sensing, the eABTL-based methods have the potential to be a crucial part of ES techniques for environmental and industrial monitoring.
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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.
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Biomassa , Carbono , Corantes Fluorescentes , Carbono/análise , Carbono/química , Pontos Quânticos/análise , Pontos Quânticos/química , Plantas , Estrutura MolecularRESUMO
Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.
Assuntos
Anticorpos Monoclonais Humanizados , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Compostos de Platina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Resposta Patológica Completa , Antineoplásicos/uso terapêutico , Terapia Combinada , Compostos de Platina/administração & dosagem , Compostos de Platina/uso terapêutico , IdosoRESUMO
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.
RESUMO
Multiple-input multiple-output (MIMO) detectors have been a key technology in communication systems. In this paper, a new MIMO detector is designed by combining the adaptive learning rate (ALR) with the convolutional neural network (CNN) and successfully implementing it in a mode division multiplexing (MDM) optical transmission system. The results show that the training and test accuracy of the signal in the system we proposed reaches 100%. What is more, we used the ALR-CNN to compare the performance with conventional detection algorithms. The results confirm that our DLNN exceeds the conventional MIMO detectors in performance and is able to achieve the ideal QPSK BER level. The minimum difference in the SNR is about 9.5 dB at a BER of the 10-3 order.