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Phytochromes are red light (R) and far-red light (FR) receptors that play important roles in many aspects of plant growth and development. Phytochromes mainly function in the nucleus and regulate sets of genes by inhibiting negatively acting basic helix-loop-helix transcription factors named PHYTOCHROME INTERACTING FACTORs (PIFs) in Arabidopsis thaliana. Although R/FR photoreversible responses and phytochrome genes are well documented in diverse lineages of plants, the extent to which phytochrome signaling is mediated by gene regulation beyond angiosperms remains largely unclear. Here, we show that the liverwort Marchantia polymorpha, an emerging model basal land plant, has only one phytochrome gene, Mp-PHY, and only one PIF gene, Mp-PIF. These genes mediate typical low fluence responses, which are reversibly elicited by R and FR, and regulate gene expression. Mp-phy is light-stable and translocates into the nucleus upon irradiation with either R or FR, demonstrating that the single phytochrome Mp-phy exhibits combined biochemical and cell-biological characteristics of type I and type II phytochromes. Mp-phy photoreversibly regulates gemma germination and downstream gene expression by interacting with Mp-PIF and targeting it for degradation in an R-dependent manner. Our findings suggest that the molecular mechanisms for light-dependent transcriptional regulation mediated by PIF transcription factors were established early in land plant evolution.

Ammonia is an important chemical feedstock and is produced by Ru or Fe catalyst so far. We investigated Co catalyst for low temperature ammonia synthesis in an electric field. Well-reduced Co/Ce 0.5 Zr 0.5 O 2 catalyst showed high activity for ammonia synthesis even at 473 K in the electric field. Various characterizations including kinetic tests, operando DRIFTS measurements, TEM observations, and XAFS measurements, revealed that the active site is the interface between supported Co and Ce 0.5 Zr 0.5 O 2 oxide support, thanks to the surface protonics derived from an electric field. Graphical Abstract

To date, there have been no head-to-head randomized controlled trials (RCTs) comparing the safety and efficacy of lorlatinib and alectinib in anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) ALK-inhibitor‒naïve advanced non-small cell lung cancer (NSCLC). We performed a network meta-analysis comparing six treatment arms (lorlatinib, brigatinib, alectinib, ceritinib, crizotinib, and platinum-based chemotherapy) in overall participants and in Asian and non-Asian subgroups. Primary endpoints were progression-free survival (PFS), overall survival (OS), and grade 3 or higher adverse events (G3-AEs). There were no significant differences between lorlatinib and alectinib in overall participants for both PFS (hazard ratio [HR], 0.742; 95% credible interval [CrI], 0.466–1.180) and OS (HR, 1.180; 95% CrI, 0.590–2.354). In the Asian subgroup, there were no significant differences in PFS between lorlatinib and alectinib (HR, 1.423; 95% CrI, 0.748–2.708); however, in the non-Asian subgroup, PFS was significantly better with lorlatinib than with alectinib (HR, 0.388; 95% CrI, 0.195–0.769). The incidence of G3-AEs in overall participants was significantly higher with lorlatinib than with alectinib (risk ratio, 1.918; 95% CrI, 1.486–2.475). These results provide valuable information regarding the safety and efficacy of lorlatinib in ALK-p ALK-inhibitor‒naïve advanced NSCLC. Larger head-to-head RCTs are needed to validate the study results.

The Renin-Angiotensin system (RAS) induces immunosuppression in the tumor microenvironment, and RAS inhibitors (RASi) improve the tumor immune microenvironment. We evaluated the impact of RASi on the efficacy anti-programmed cell death-1/Ligand-1 (anti-PD-1/PD-L1) antibodies. This retrospective study analyzed non-small cell lung cancer (NSCLC) patients who received anti-PD-1/PD-L1 antibodies monotherapy as second- or later-line treatment. We classified patients into those with or without use of RASi. A total of 256 NSCLC patients were included and 37 patients used RASi. The median PFS of patients treated with RASi was significantly longer than that of patients treated without (HR=0.59, 95%CI=0.40-0.88). The median OS of patients treated with RASi tended to be longer than that of patients treated without (HR=0.71, 95%CI=0.45-1.11). The use of RASi was associated with a significantly longer PFS in NSCLC patients treated with anti-PD-1/PD-L1 antibodies. RASi use may enhance the efficacy of anti-PD-1/PD-L1 antibodies.

Catalytic water gas shift for hydrogen production in the temperature range of 423–873 K, was examined imposing an electric field to the catalyst bed. Reaction trends were investigated based on thermodynamic equilibrium and chemical kinetic law. Pt/La–ZrO 2 was chosen as an active catalyst through our screening tests, and the effect of the electric field on the catalytic activity was investigated by changing reaction temperatures and applied electric currents. Although the reaction was ruled by thermodynamic equilibrium at high temperatures, drastic promotion of the reaction by applying the electric field was observed at low temperatures in a kinetic region. Drastic decrease of apparent activation energy for WGS was observed by imposing the electric field to the catalyst bed. Various isotopic transient tests revealed that the reaction mechanism changed by the application of electric field, and redox mechanism using surface lattice oxygen played an important role in case of the catalytic WGS in the electric field. Graphical Abstract

The development of simple catalysts with high performance in the selective oxidation of methane to syngas at low temperature has attracted much attention. Here we report a nickel-based solid catalyst for the oxidation of methane, synthesised by a facile impregnation method. Highly dispersed ultra-small NiO particles of 1.6 nm in size are successfully formed on the MOR-type zeolite. The zeolite–supported nickel catalyst gives continuously 97–98% methane conversion, 91–92% of CO yield with a H 2 /CO ratio of 2.0, and high durability without serious carbon deposition onto the catalyst at 973 K. DFT calculations demonstrate the effect of NiO particle size on the C-H dissociation process of CH 4 . A decrease in the NiO particle size enhances the production of oxygen originating from the NiO nanoparticles, which contributes to the oxidation of methane under a reductive environment, effectively producing syngas. Catalytic oxidation of methane to syngas is an important process, but efficient and stable catalyts remain in demand. Here dispersion of nickel on zeolites yields nickel oxide nanoparticles as small as 1.6 nm which act as selective and efficient catalysts for conversion of methane to syngas.

Homeostasis is achieved by balancing cell survival and death. In cancer cells, especially those carrying driver mutations, the processes and signals that promote apoptosis are inhibited, facilitating the survival and proliferation of these dysregulated cells. Apoptosis induction is an important mechanism underlying the therapeutic efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for EGFR-mutated non-small cell lung cancer (NSCLC). However, the mechanisms by which EGFR-TKIs induce apoptosis have not been fully elucidated. A deeper understanding of the apoptotic pathways induced by EGFR-TKIs is essential for the developing novel strategies to overcome resistance to EGFR-TKIs or to enhance the initial efficacy through therapeutic synergistic combinations. Recently, therapeutic strategies targeting apoptosis have been developed for cancer. Here, we review the state of knowledge on EGFR-TKI-induced apoptotic pathways and discuss the therapeutic strategies for enhancing EGFR-TKI efficiency. We highlight the great progress achieved with third-generation EGFR-TKIs. In particular, combination therapies of EGFR-TKIs with anti-vascular endothelial growth factor/receptor inhibitors or chemotherapy have emerged as promising therapeutic strategies for patients with EGFR-mutated NSCLC. Nevertheless, further breakthroughs are needed to yield an appropriate standard care for patients with EGFR-mutated NSCLC, which requires gaining a deeper understanding of cancer cell dynamics in response to EGFR-TKIs.

Background The relationship between the combination of platelet count and neutrophil‐lymphocyte ratio (COP‐NLR) and prognosis in patients with advanced non‐small cell lung cancer (NSCLC) treated with immune checkpoint inhibitor (ICI) combination therapy with chemotherapy remains unclear. Thus, we investigated prognostic factors, including the COP‐NLR, to identify patients who could benefit from the therapeutic efficacy of ICI combination therapy for advanced NSCLC. Furthermore, we evaluated the relationship between the COP‐NLR score during ICI combination therapy and treatment response. Methods We conducted a retrospective cohort study of 88 patients with NSCLC who initially received ICI combination therapy. The primary outcome was overall survival (OS). The prognostic factors were extracted using the Cox proportional hazards model. The relationship between COP‐NLR score at 3 weeks after starting ICI combination therapy and a good response (complete response [CR] and partial response [PR]) to treatment was analyzed using the chi‐square test. Results The median OS was 15.7 months. In the multivariable analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2, distant metastatic sites ≥2, and baseline COP‐NLR scores of 1, 2 were extracted as significant poor prognostic factors. The proportion of patients with CR and PR in the 3‐week COP‐NLR score of 0 group was significantly higher than that in scores of 1, 2 group. Conclusions Baseline COP‐NLR, ECOG PS, and number of distant metastatic sites were prognostic factors in patients with NSCLC with ICI combination therapy. A lower 3‐week COP‐NLR was associated with a good response to treatment. We conducted a retrospective cohort study of 88 patients with non‐small cell lung cancer (NSCLC) who initially received immune checkpoint inhibitor (ICI) combination therapy with chemotherapy to identify prognostic factors, including the combination of platelet count and neutrophil‐lymphocyte ratio (COP‐NLR). Our results suggested that baseline COP‐NLR was a prognostic factor, and a lower 3‐week COP‐NLR was associated with a good response to treatment. COP‐NLR is an important indicator for selecting patients who could benefit from the therapeutic efficacy of ICI combination therapy with chemotherapy.

Background As an epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI), osimertinib has emerged as a standard EGFR‐mutation positive treatment for non‐small cell lung cancer (NSCLC). However, the efficacy of osimertinib for malignant pleural effusion (MPE) remains understudied. This study aimed to evaluate the impact of osimertinib on time to treatment failure (TTF) and overall survival (OS) in patients with EGFR‐mutation positive NSCLC, comparing those with and without MPE. Methods This retrospective analysis included patients with advanced or recurrent NSCLC treated with osimertinib at our hospital between April 2016 and June 2021. TTF was defined as the duration from osimertinib initiation to discontinuation, and OS as the duration until death, irrespective of the reason. Results Among 229 patients receiving osimertinib, 84 had MPE before administration, 39 acquired EGFR exon20 T790M mutation following previous EGFR‐TKI therapy, and 45 were EGFR‐TKI‐naive. Among EGFR‐TKI‐naive patients, median TTF was 14.8 and 19.8 months for those with and without MPE, respectively (hazard ratio [HR] 1.40; 95% confidence interval [CI]: 0.90–2.18; p = 0.12). Median OS was 32.0 and 42.0 months for patients with and without MPE, respectively (HR 1.43; 95% CI: 0.86–2.38; p = 0.16). Among patients with T790M mutation, median TTF was 12.3 and 13.1 months for patients with and without MPE, respectively (HR 1.03; 95% CI: 0.69–1.55; p = 0.88). Median OS for patients with and without MPE was 23.2 and 24.7 months, respectively (HR 1.09; 95% CI: 0.72–1.67; p = 0.68). Conclusion Among patients with EGFR‐mutation positive NSCLC, the evidence of MPE has little effect on survival with osimertinib. Among patients with EGFR‐mutation positive NSCLC, the evidence of MPE has little effect on survival with osimertinib.

Background The usefulness of the Oncomine Dx Target test (Oncomine Dx), a next‐generation sequencing (NGS) test, has already been proven in clinical trials. However, NGS requires high‐quality tumor samples and takes a long time to generate results. The feasibility of NGS for use in advanced non‐small cell lung cancer (NSCLC) patients in clinical practice has not yet been determined. Methods Patients serially diagnosed with advanced NSCLC were evaluated in our hospital. The Oncomine Dx, Cobas EGFR mutation test (Cobas EGFR), and ALK‐IHC were performed. The patients were divided into four sets: the full analysis set (FAS) that referred to patients diagnosed with NSCLC, the intent to perform companion diagnostics (CDx) set (IPS) that referred to patients in which CDx had been ordered regardless of sample quality, the per‐performed CDx set (PPS) that referred to patients who could undergo CDx regardless of the results, and the per‐completed CDx set (CCS) that referred to patients in which informative results were received from the CDx. Results The total number of patients analyzed in the study was 167. The IPS/FAS of Oncomine Dx (80.2%) was lower than that of the ALK‐IHC (85.0%) and Cobas EGFR (92.8%). The CCS/FAS of Oncomine Dx (65.9%) was lower than that of the ALK‐IHC (82.0%) and Cobas EGFR (92.2%). PPS/IPS and CCS/PPS of the Oncomine Dx with nonsurgical biopsy ranged between 78.6% and 90.9%, which was lower than those patients who underwent surgical resection (95.0% and 100%). Conclusions The feasibility of Oncomine Dx in clinical practice was lower than the other CDx. The feasibility of Oncomine Dx will increase by improving the biopsy procedure. Key points Significant study findings The usefulness of a next‐generation sequencing (NGS) test has been proven in clinical trials. The feasibility of NGS is lower than other diagnostics in clinical practice especially with regard to nonsurgical biopsy. What this study adds It is necessary to improve the feasibility of NGS in clinical practice. To improve NGS feasibility, turnaround time must be shortened, and larger samples must be obtained during surgical procedures. The feasibility of Oncomine Dx in clinical practice is relatively low compared with that of the ALK‐IHC and Cobas EGFR.