DataSheet_1_The Predictive Value of Pretreatment Lactate Dehydrogenase and Derived Neutrophil-to-Lymphocyte Ratio in Advanced Non-Small Cell Lung Cancer Patients Treated With PD-1/PD-L1 Inhibitors: A Meta-Analysis.docx

BackgroundThe Lung Immune Prognostic Index (LIPI) combines the lactate dehydrogenase (LDH) level and the derived neutrophil-to-lymphocyte ratio (dNLR). A lot of studies have shown that LDH and dNLR are associated with the prognosis of advanced non-small cell lung cancer (NSCLC) in patients treated with programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors. However, previous results were inconsistent, and the conclusions remain unclear. This meta-analysis aimed to investigate the predictive value of pretreatment LDH and dNLR for NSCLC progression in patients treated with PD-1/PD-L1 inhibitors.MethodsPubMed, Embase, and the Cochrane Library were searched by two researchers independently for related literature before March 2020. Hazard ratios (HRs) with 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) were extracted to assess the predictive value of LDH and dNLR. STATA 15. 0 was used to perform the meta-analysis.ResultsA total of 3,429 patients from 26 studies were included in this meta-analysis. The results revealed that high pretreatment LDH was related to poor OS (HR = 1.19, 95%CI = 1.11–1.24, p ConclusionBoth pretreatment LDH and dNLR have the potential to serve as peripheral blood biomarkers for patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors. However, more studies on LDH are needed to evaluate its predictive value for PFS in patients with NSCLC.</p

DataSheet_1_Association of Brain Metastases With Immune Checkpoint Inhibitors Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis.docx

BackgroundIn pivotal immunotherapy trials, the efficacy of immune checkpoint inhibitors as treatments for lung cancer patients with brain metastases remains controversial. The aim of this study was to assess the relative efficacy of immunotherapy versus standard systemic therapy in advanced lung cancer patients with and without brain metastases.MethodsSystematic searches of PubMed, Embase, Cochrane database, and conference proceedings up to Aug 6, 2020 without year and language restrictions. The main outcomes were the overall survival in patients with and without brain metastases measured by hazard ratios, and the difference in efficacy between patients with and without brain metastases was measured by ratio of hazard ratios.ResultsNine eligible randomized controlled trials involving 6241 patients (682 [11%] with brain metastases and 5559 [89%] without brain metastases) were included in the analysis. A survival benefit of immunotherapy was observed for both patients with brain metastases (HR, 0.75; 95%CI, 0.53-0.97; P = .026) and patients without brain metastases (HR, 0.75; 95%CI, 0.67-0.83; P ConclusionsImmunotherapy can significantly improve overall survival for advanced lung cancer patients with asymptomatic brain metastases, especially in patients with non-small-cell lung cancer, but the magnitude of benefit is brain metastases dependent.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020206597.</p

Table_1_Anti-Angiogenic Drugs Inhibit Interstitial Lung Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer.docx

BackgroundInterstitial lung disease (ILD) is the most serious complication of chemotherapy in lung cancer patients with pre-existing ILD. The effect of anti-angiogenic drugs in lung cancer patients with ILD remains unclear. We examined the effect of anti-angiogenic drugs on reducing the risk of ILD progression in non-small cell lung cancer (NSCLC) patients receiving chemotherapy.MethodsWe analyzed the risk of ILD progression in 52 patients with advanced NSCLC with ILD who received first-line chemotherapy with (anti-angiogenic group, n = 22) and without (non-anti-angiogenic group, n = 30) anti-angiogenic drugs between August 2014 and January 2021.ResultsThe incidences of chemotherapy-related ILD progression were significantly lower in the anti-angiogenic than in the non-anti-angiogenic groups (0% vs. 20.0%, p = 0.033). However, there were no differences in other events as the competing risk factors of ILD progression between the two groups. The overall-cumulative incidence of ILD progression during the first-line and subsequent chemotherapy was 30.8% (16 of the 52). The median progression-free survival had no significant difference between the anti-angiogenic and the non-anti-angiogenic groups (10.3 vs. 8.1 months, p = 0.386).ConclusionsThe addition of anti-angiogenic drugs to chemotherapy regimens may reduce the risk of chemotherapy-related ILD progression in patients with NSCLC-ILD.</p

Table_7_Transcriptomic and Proteomic Analysis of Shaan2A Cytoplasmic Male Sterility and Its Maintainer Line in Brassica napus.XLSX

Cytoplasmic male sterility (CMS) lines are widely used for hybrid production in Brassica napus. The Shaan2A CMS system is one of the most important in China and has been used for decades; however, the male sterility mechanism underlying Shaan2A CMS remains unknown. Here, we performed transcriptomic and proteomic analysis, combined with additional morphological observation, in the Shaan2A CMS. Sporogenous cells, endothecium, middle layer, and tapetum could not be clearly distinguished in Shaan2A anthers. Furthermore, Shaan2A anther chloroplasts contained fewer starch grains than those in Shaan2B (a near-isogenic line of Shaan2A), and the lamella structure of chloroplasts in Shaan2A anther wall cells was obviously aberrant. Transcriptomic analysis revealed differentially expressed genes (DEGs) mainly related to carbon metabolism, lipid and flavonoid metabolism, and the mitochondrial electron transport/ATP synthesis pathway. Proteomic results showed that differentially expressed proteins were mainly associated with carbohydrate metabolism, energy metabolism, and genetic information processing pathways. Importantly, nine gene ontology categories associated with anther and pollen development were enriched among down-regulated DEGs at the young bud (YB) stage, including microsporogenesis, sporopollenin biosynthetic process, and tapetal layer development. Additionally, 464 down-regulated transcription factor (TF) genes were identified at the YB stage, including some related to early anther differentiation such as SPOROCYTELESS (SPL, also named NOZZLE, NZZ), DYSFUNCTIONAL TAPETUM 1 (DYT1), MYB80 (formerly named MYB103), and ABORTED MICROSPORES (AMS). These results suggested that the sterility gene in the Shaan2A mitochondrion might suppress expression of these TF genes in the nucleus, affecting early anther development. Finally, we constructed an interaction network of candidate proteins based on integrative analysis. The present study provides new insights into the molecular mechanism of Shaan2A CMS in B. napus.</p

Table_6_Transcriptomic and Proteomic Analysis of Shaan2A Cytoplasmic Male Sterility and Its Maintainer Line in Brassica napus.XLSX

Cytoplasmic male sterility (CMS) lines are widely used for hybrid production in Brassica napus. The Shaan2A CMS system is one of the most important in China and has been used for decades; however, the male sterility mechanism underlying Shaan2A CMS remains unknown. Here, we performed transcriptomic and proteomic analysis, combined with additional morphological observation, in the Shaan2A CMS. Sporogenous cells, endothecium, middle layer, and tapetum could not be clearly distinguished in Shaan2A anthers. Furthermore, Shaan2A anther chloroplasts contained fewer starch grains than those in Shaan2B (a near-isogenic line of Shaan2A), and the lamella structure of chloroplasts in Shaan2A anther wall cells was obviously aberrant. Transcriptomic analysis revealed differentially expressed genes (DEGs) mainly related to carbon metabolism, lipid and flavonoid metabolism, and the mitochondrial electron transport/ATP synthesis pathway. Proteomic results showed that differentially expressed proteins were mainly associated with carbohydrate metabolism, energy metabolism, and genetic information processing pathways. Importantly, nine gene ontology categories associated with anther and pollen development were enriched among down-regulated DEGs at the young bud (YB) stage, including microsporogenesis, sporopollenin biosynthetic process, and tapetal layer development. Additionally, 464 down-regulated transcription factor (TF) genes were identified at the YB stage, including some related to early anther differentiation such as SPOROCYTELESS (SPL, also named NOZZLE, NZZ), DYSFUNCTIONAL TAPETUM 1 (DYT1), MYB80 (formerly named MYB103), and ABORTED MICROSPORES (AMS). These results suggested that the sterility gene in the Shaan2A mitochondrion might suppress expression of these TF genes in the nucleus, affecting early anther development. Finally, we constructed an interaction network of candidate proteins based on integrative analysis. The present study provides new insights into the molecular mechanism of Shaan2A CMS in B. napus.</p

Table_3_Transcriptomic and Proteomic Analysis of Shaan2A Cytoplasmic Male Sterility and Its Maintainer Line in Brassica napus.XLSX

Cytoplasmic male sterility (CMS) lines are widely used for hybrid production in Brassica napus. The Shaan2A CMS system is one of the most important in China and has been used for decades; however, the male sterility mechanism underlying Shaan2A CMS remains unknown. Here, we performed transcriptomic and proteomic analysis, combined with additional morphological observation, in the Shaan2A CMS. Sporogenous cells, endothecium, middle layer, and tapetum could not be clearly distinguished in Shaan2A anthers. Furthermore, Shaan2A anther chloroplasts contained fewer starch grains than those in Shaan2B (a near-isogenic line of Shaan2A), and the lamella structure of chloroplasts in Shaan2A anther wall cells was obviously aberrant. Transcriptomic analysis revealed differentially expressed genes (DEGs) mainly related to carbon metabolism, lipid and flavonoid metabolism, and the mitochondrial electron transport/ATP synthesis pathway. Proteomic results showed that differentially expressed proteins were mainly associated with carbohydrate metabolism, energy metabolism, and genetic information processing pathways. Importantly, nine gene ontology categories associated with anther and pollen development were enriched among down-regulated DEGs at the young bud (YB) stage, including microsporogenesis, sporopollenin biosynthetic process, and tapetal layer development. Additionally, 464 down-regulated transcription factor (TF) genes were identified at the YB stage, including some related to early anther differentiation such as SPOROCYTELESS (SPL, also named NOZZLE, NZZ), DYSFUNCTIONAL TAPETUM 1 (DYT1), MYB80 (formerly named MYB103), and ABORTED MICROSPORES (AMS). These results suggested that the sterility gene in the Shaan2A mitochondrion might suppress expression of these TF genes in the nucleus, affecting early anther development. Finally, we constructed an interaction network of candidate proteins based on integrative analysis. The present study provides new insights into the molecular mechanism of Shaan2A CMS in B. napus.</p

Table_4_Transcriptomic and Proteomic Analysis of Shaan2A Cytoplasmic Male Sterility and Its Maintainer Line in Brassica napus.XLSX

Cytoplasmic male sterility (CMS) lines are widely used for hybrid production in Brassica napus. The Shaan2A CMS system is one of the most important in China and has been used for decades; however, the male sterility mechanism underlying Shaan2A CMS remains unknown. Here, we performed transcriptomic and proteomic analysis, combined with additional morphological observation, in the Shaan2A CMS. Sporogenous cells, endothecium, middle layer, and tapetum could not be clearly distinguished in Shaan2A anthers. Furthermore, Shaan2A anther chloroplasts contained fewer starch grains than those in Shaan2B (a near-isogenic line of Shaan2A), and the lamella structure of chloroplasts in Shaan2A anther wall cells was obviously aberrant. Transcriptomic analysis revealed differentially expressed genes (DEGs) mainly related to carbon metabolism, lipid and flavonoid metabolism, and the mitochondrial electron transport/ATP synthesis pathway. Proteomic results showed that differentially expressed proteins were mainly associated with carbohydrate metabolism, energy metabolism, and genetic information processing pathways. Importantly, nine gene ontology categories associated with anther and pollen development were enriched among down-regulated DEGs at the young bud (YB) stage, including microsporogenesis, sporopollenin biosynthetic process, and tapetal layer development. Additionally, 464 down-regulated transcription factor (TF) genes were identified at the YB stage, including some related to early anther differentiation such as SPOROCYTELESS (SPL, also named NOZZLE, NZZ), DYSFUNCTIONAL TAPETUM 1 (DYT1), MYB80 (formerly named MYB103), and ABORTED MICROSPORES (AMS). These results suggested that the sterility gene in the Shaan2A mitochondrion might suppress expression of these TF genes in the nucleus, affecting early anther development. Finally, we constructed an interaction network of candidate proteins based on integrative analysis. The present study provides new insights into the molecular mechanism of Shaan2A CMS in B. napus.</p

Genome-wide analysis of intron retention in RES complex mutants.

<p><b>(A)</b> Schematic representation of intron features analyzed in (B) and (C). Top: Intron position. “Internal” introns correspond to all introns excluding the first two and last three introns. Bottom: NMD vs non-NMD triggering introns. Introns predicted to cause NMD upon retention introduce a premature termination codon (PTC) further than 50 nucleotides upstream of an exon-exon junction. Introns predicted not to cause NMD (noNMD) may correspond to: (i) last introns, (ii) introns in UTRs or non-coding genes, or (iii) introns that preserved the ORF upon retention (multiple of three nucleotides with no in-frame stop codons). <b>(B)</b> Box plots showing the ∆PIR of last and internal introns in the three different mutant of the RES complex. Only genes with more than 10 introns were considered for the analysis. <i>bud13</i> *** <i>P</i> = 4.37x10^-201; <i>rbmx2</i> *** <i>P</i> = 2.98x10^-202; <i>snip1</i> *** <i>P</i> = 4.76x10^-195 (Wilcoxon rank sum test). <b>(C)</b> Box plots showing the ∆PIR of introns predicted to trigger nonsense mediated decay (NMD) upon retention and those predicted not to trigger NMD (no-NMD) in the three different mutant of the RES complex. <i>bud13</i> *** <i>P</i> = 5.83x10^-208; <i>rbmx2</i> *** <i>P</i> = 4.94x10^-184; <i>snip1</i> *** <i>P</i> = 1.74x10^-183 (Wilcoxon rank sum test).</p

Image_1_Transcriptomic and Proteomic Analysis of Shaan2A Cytoplasmic Male Sterility and Its Maintainer Line in Brassica napus.JPEG

Cytoplasmic male sterility (CMS) lines are widely used for hybrid production in Brassica napus. The Shaan2A CMS system is one of the most important in China and has been used for decades; however, the male sterility mechanism underlying Shaan2A CMS remains unknown. Here, we performed transcriptomic and proteomic analysis, combined with additional morphological observation, in the Shaan2A CMS. Sporogenous cells, endothecium, middle layer, and tapetum could not be clearly distinguished in Shaan2A anthers. Furthermore, Shaan2A anther chloroplasts contained fewer starch grains than those in Shaan2B (a near-isogenic line of Shaan2A), and the lamella structure of chloroplasts in Shaan2A anther wall cells was obviously aberrant. Transcriptomic analysis revealed differentially expressed genes (DEGs) mainly related to carbon metabolism, lipid and flavonoid metabolism, and the mitochondrial electron transport/ATP synthesis pathway. Proteomic results showed that differentially expressed proteins were mainly associated with carbohydrate metabolism, energy metabolism, and genetic information processing pathways. Importantly, nine gene ontology categories associated with anther and pollen development were enriched among down-regulated DEGs at the young bud (YB) stage, including microsporogenesis, sporopollenin biosynthetic process, and tapetal layer development. Additionally, 464 down-regulated transcription factor (TF) genes were identified at the YB stage, including some related to early anther differentiation such as SPOROCYTELESS (SPL, also named NOZZLE, NZZ), DYSFUNCTIONAL TAPETUM 1 (DYT1), MYB80 (formerly named MYB103), and ABORTED MICROSPORES (AMS). These results suggested that the sterility gene in the Shaan2A mitochondrion might suppress expression of these TF genes in the nucleus, affecting early anther development. Finally, we constructed an interaction network of candidate proteins based on integrative analysis. The present study provides new insights into the molecular mechanism of Shaan2A CMS in B. napus.</p

Table_2_Transcriptomic and Proteomic Analysis of Shaan2A Cytoplasmic Male Sterility and Its Maintainer Line in Brassica napus.XLSX

Cytoplasmic male sterility (CMS) lines are widely used for hybrid production in Brassica napus. The Shaan2A CMS system is one of the most important in China and has been used for decades; however, the male sterility mechanism underlying Shaan2A CMS remains unknown. Here, we performed transcriptomic and proteomic analysis, combined with additional morphological observation, in the Shaan2A CMS. Sporogenous cells, endothecium, middle layer, and tapetum could not be clearly distinguished in Shaan2A anthers. Furthermore, Shaan2A anther chloroplasts contained fewer starch grains than those in Shaan2B (a near-isogenic line of Shaan2A), and the lamella structure of chloroplasts in Shaan2A anther wall cells was obviously aberrant. Transcriptomic analysis revealed differentially expressed genes (DEGs) mainly related to carbon metabolism, lipid and flavonoid metabolism, and the mitochondrial electron transport/ATP synthesis pathway. Proteomic results showed that differentially expressed proteins were mainly associated with carbohydrate metabolism, energy metabolism, and genetic information processing pathways. Importantly, nine gene ontology categories associated with anther and pollen development were enriched among down-regulated DEGs at the young bud (YB) stage, including microsporogenesis, sporopollenin biosynthetic process, and tapetal layer development. Additionally, 464 down-regulated transcription factor (TF) genes were identified at the YB stage, including some related to early anther differentiation such as SPOROCYTELESS (SPL, also named NOZZLE, NZZ), DYSFUNCTIONAL TAPETUM 1 (DYT1), MYB80 (formerly named MYB103), and ABORTED MICROSPORES (AMS). These results suggested that the sterility gene in the Shaan2A mitochondrion might suppress expression of these TF genes in the nucleus, affecting early anther development. Finally, we constructed an interaction network of candidate proteins based on integrative analysis. The present study provides new insights into the molecular mechanism of Shaan2A CMS in B. napus.</p