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N2O is one of the most important greenhouse gases and ozone depletor, which was a matter of more and more concerned. The Southern Ocean was considered as one of the most important N2O source and was believed to account for ~1/4 of oceanic budget. However, there is uncertainty about this budget due to limited data availability. In this study, field and lab works were conducted for better understanding of N2O dynamics during sea ice melting and sea ice formation. In the field study, taking advantage of the Chinese Antarctic cruise, a 10 days’ time series study was carried out at a station in the Prydz Bay, Antarctica, where, surface water N2O was observed continuously, and the adjacent ice cores were taken for N2O analysis. In the lab, an ice growing simulation system was constructed to study the N2O dynamics during the sea ice formation. The result of endmember mixing models and calculation of N2O partition in three phases during sea ice formation provide important information about the dynamics of N2O during ice melting and sea ice formation processes, that is, the sea ice melting regulated N2O concentration and saturation status, which can be an explanation for reported N2O undersaturation observed in polar oceans, whereas during the sea ice formation, most of the N2O will be expelled to the deeper water while a small amount of retain the sea ice and less amount of N2O release to the atmosphere.

AimThis research aimed to explore the causal impact of blood metabolites on oral cancer using a two-sample Mendelian randomization (MR) analysis. The study endeavored to identify potential biomarkers for oral cancer’s clinical management.Materials and methodsBased on the large individual-level datasets from UK Biobank as well as GWAS summary datasets, we first constructed genetic risk scores (GRSs) of 486 human blood metabolites and evaluated the effect on oral cancer. Various statistical methods, including inverse variance weighted (IVW), MR-Egger, and weighted median, among others, were employed to analyze the potential causal relationship between blood metabolites and oral cancer. The sensitivity analyses were conducted using Cochran’s Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests.Results29 metabolites met the stringent selection criteria. Out of these, 14 metabolites demonstrated a positive association with oral cancer risk, while 15 metabolites indicated a protective effect against oral cancer. The IVW-derived estimates were significant, and the results were consistent across different statistical methodologies. Both the Cochran Q test and the MR-Egger intercept test indicated no heterogeneity and pleiotropy.ConclusionThis MR study offers evidence of the role specific blood metabolites play in oral cancer, pinpointing several with potential risk or protective effects. These findings could be helpful for new diagnostic tools and treatments for oral cancer. While the results are promising, additional research is necessary to fully validate and refine these conclusions. This study serves as a foundational step towards more comprehensive understandings in the future.

Nitrous oxide (N2O) is one of the most important greenhouse gases and contributes to the depletion of ozone in the stratosphere. Estuaries are areas of intensive biological production and associated N2O emissions through both denitrification and nitrification processes. The spatial and temporal variations of N2O in the Jiulong River Estuary, a subtropical estuary, were explored to evaluate sources and sinks of N2O in this area. The estuary was found to be a strong source of N2O, its saturation in the surface water ranged from 113 to 2926% relative to the ambient atmospheric concentrations, showing great temporal and spatial variations and was influenced by multiple factors such as the concentration of dissolved inorganic nitrogen (DIN, i.e., NO3−,NH4+, and NO2−), salinity and dissolved oxygen. N2O concentrations were at a high level in upper estuary but reduced to the lower parts of the estuary. Groundwater input could be another contributor to N2O in the estuary. Almost all N2O within the estuary was released into the atmosphere rather than being transported to the bay. The N2O flux in the estuary (mean 597 μmol/m2/d) was at the higher end of the range observed in estuaries worldwide due to the very high DIN loads in the Jiulong River Estuary. Our data indicate that the N2O saturation in the estuary continues to increase, although the DIN inputs began to decline in 2011, which might be relate to the improved environmental conditions with increased oxygen concentrations. N2O production pathways have changed from predominantly denitrification in the past toward significant production from nitrification in the present. Further investigation is needed to better understand the behavior of N2O in the Jiulong River Estuary.

Background and ObjectiveImmune checkpoint inhibitor (ICI)-associated myocarditis is a fatal immune-related adverse events (irAEs), which is prone to affecting multiple organ systems. Multi-organ irAEs have not been fully studied in ICI-associated myocarditis. Therefore, we aimed to explore the impact of multi-organ irAEs on ICI myocarditis in terms of clinical features, treatment, and prognosis.MethodsThis was a retrospective study. The clinical data of ICI myocarditis patients were collected from 6 hospitals in China. The risk factors and characteristics of pure myocarditis and multi-organ irAEs were analyzed. The overall survival (OS) after myocarditis was analyzed and univariate and multivariate regression analysis were performed.ResultsA total of 46 patients were analyzed in this study. Multi-organ irAEs were common (30/46, 65.2%) and prone to severe heart failure. The severe myocarditis was observed in 32 patients (69.6%). When myocarditis occurred, neutrophil to lymphocyte ratio, C-reactive protein, lactate dehydrogenase, interleukin (IL)-6, IL-10, creatine kinase, MB isoenzyme of creatine kinase, and brain natriuretic peptide increased from baseline, but absolute lymphocyte count decreased. Thymoma (B2/B3) was a risk factor for multi-organ irAEs. Heart failure and myocarditis were more severe in patients with multi-organ irAEs and require early corticosteroid therapy (

BackgroundPALB2, a gene in the homologous recombination repair (HRR) pathway of the DNA damage response (DDR), is associated with the efficacy of platinum-based chemotherapy, immunotherapy, and PARP inhibitor therapy in several tumors. However, the PALB2 characteristics, its correlation with immunotherapy biomarker, and the prognostic effect of immunotherapy in non-small cell lung cancer (NSCLC) were unknown.MethodsTumor tissue samples from advanced Chinese NSCLC patients were analyzed by next-generation sequencing (NGS) (panel on 381/733-gene). Tumor mutation burden (TMB) is defined as the total number of somatic non-synonymous mutations in the coding region. Microsatellite instability (MSI) was evaluated by NGS of 500 known MSI loci. Programmed Cell Death-Ligand 1 (PD-L1) expression was evaluated using immunohistochemistry (Dako 22C3 or SP263). One independent cohort (Rizvi2018.NSCLC.240.NGS cohort) containing genomic and clinical data from 240 patients with advanced NSCLC and two cohorts (the OAK and POPLAR study cohort) containing genomic and clinical data from 429 patients with advanced NSCLC were used to analyze the prognostic effect of PALB2 on immunotherapy.ResultsGenetic mutation of 5,227 NSCLC patients were analyzed using NGS, of which 162 (3.1%) harbored germline PALB2 mutation (PALB2gmut) and 87 (1.66%) harbored somatic PALB2 mutation (PALB2smut). In NSCLC patients with PALB2gmut and PALB2smut, the most frequently mutated gene was TP53 (65%, 64%). PALB2smut (14.52 Muts/Mb) was associated with higher TMB (p < 0.001) than PALB wild-type (PALB2wt) (6.15 Muts/Mb). However, there was no significant difference in TMB between PALB2gmut (6.45 Muts/Mb) and PALB2wt (6.15 Muts/Mb) (p = 0.64). There was no difference in PD-L1 expression among PALB2gmut, PALB2smut, and PALB2wt. In the Rizvi2018.NSCLC.240.NGS cohort, there was no difference in progression-free survival (PFS) (HR =1.06, p = 0.93) between PALB2 mutation (3.15 months) and PALB2wt (3.17 months). The OAK and POPLAR study cohort of NSCLC patients showed that there was no difference in overall survival (OS) (HR =1.1, p = 0.75) between PALB2 mutation (10.38 months) and PALB2wt (11.07 months).ConclusionsThese findings suggest that PALB2 may not be used as a biomarker for determining prognosis on immunotherapy in NSCLC.