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ObjectivesProgrammed death-ligand 1 (PD-L1) is the only Food and Drug Administration-approved biomarker for monitoring response to immune checkpoint inhibitor (ICI) therapy in patients with lung adenocarcinoma. Understanding the nuances of molecular phenotypes, clinical attributes, and PD-L1 expression levels in primary and metastatic lung adenocarcinoma may help predict response to therapy and assist in the clinical management of lung adenocarcinoma.MethodsA total of 235 primary and metastatic lesion specimens from patients with non-small cell lung cancer (NSCLC) an institution in Shandong, China were analyzed. PD-L1 expression was assessed by immunohistochemistry using the 22C3 antibody, and the molecular phenotype was determined by next-generation sequencing of 450 genes. The molecular phenotypes of the primary and metastatic lesions were compared.ResultsElevated PD-L1 expression was significantly associated with advanced and metastatic disease (P = 0.001). The distribution of PD-L1 expression varied based on the anatomical location, showing a higher frequency of elevated PD-L1 expression in distal metastases than in the primary tumor. Metastatic lesions exhibited a higher proportion of carcinogenic pathway gene alterations and a greater number of DNA damage-repair pathway gene alterations than the primary lesions. Notably, CDKN2A copy number deletions were more prevalent in metastatic lesions than in primary lesions. Clinical data stemming from research conducted at the Memorial Sloan Kettering Cancer Center revealed an association between the absence of CDKN2A expression and a poorer prognosis in stage I lung adenocarcinoma.ConclusionSamples of metastatic tumors exhibited a higher proportion of elevated PD-L1 expression, a greater number of pathway alterations, and a higher occurrence of CDKN2A copy number deletions than primary samples. This highlights the importance of reinforcing the clinical management and follow-up of patients with CDKN2A deficiency, particularly within the subset of stage I lung adenocarcinoma.

Humic acids (HAs) are complex organic substances with abundant functional groups (e.g., carboxyl, phenolic-OH, etc.). They are commonly distributed in the soil environment and exert a double-edged sword effect in controlling the migration and transformation of uranium. However, the effects of HAs on dynamic processes associated with uranium transformation are still unclear. In this study, we used HAs derived from leonardite (L-HA) and commercial HA (C-HA) as exogenous organic matter and C-HA as the reference. UO2, UO3, and UO2(NO3)2 were used as the sources of U to explore the fractionations of uranium in the soil. We also studied the behavior of the HA. The incubation experiments were designed to investigate the effects of HA on the soil pH, uranium fraction transformation, dynamic behavior of exchangeable, weak acid, and labile uranium. The observations were made for one month. The results showed that soil pH decreased for L-HA but increased for C-HA. Under these conditions, uranium tended to transform into an inactive fraction. The dynamic behavior of exchangeable, weak acid, and labile uranium varied with the sources of HA and uranium. This study highlighted that HA could affect soil pH and the dynamic redistribution of U fractions. The results suggest that the sources of HA and U should be considered when using HA as the remediation material for uranium-contaminated soils.

Abstract Background Cotton fiber yield is a complex trait, which can be influenced by multiple agronomic traits. Unravelling the genetic basis of cotton fiber yield-related traits contributes to genetic improvement of cotton. Results In this study, 503 upland cotton varieties covering the four breeding stages (BS1–BS4, 1911–2011) in China were used for association mapping and domestication analysis. One hundred and forty SSR markers significantly associated with ten fiber yield-related traits were identified, among which, 29 markers showed an increasing trend contribution to cotton yield-related traits from BS1 to BS4, and 26 markers showed decreased trend effect. Four favorable alleles of 9 major loci (R 2 ≥ 3) were strongly selected during the breeding stages, and the candidate genes of the four strongly selected alleles were predicated according to the gene function annotation and tissue expression data. Conclusions The study not only uncovers the genetic basis of 10 cotton yield-related traits but also provides genetic evidence for cotton improvement during the cotton breeding process in China.

Best management practices (BMPs) for agricultural diffuse pollution control are implemented at the field or small-watershed scale. However, the benefits of BMP implementation on receiving water quality at multiple spatial is an ongoing challenge. In this paper, we introduce an integrated approach that combines risk assessment (i.e., Phosphorus (P) index), model simulation techniques (Hydrological Simulation Program-FORTRAN), and a BMP placement tool at various scales to identify the optimal location for implementing multiple BMPs and estimate BMP effectiveness after implementation. A statistically significant decrease in nutrient discharge from watersheds is proposed to evaluate the effectiveness of BMPs, strategically targeted within watersheds. Specifically, we estimate two types of cost-effectiveness curves (total pollution reduction and proportion of watersheds improved) for four allocation approaches. Selection of a ''best approach" depends on the relative importance of the two types of effectiveness, which involves a value judgment based on the random/aggregated degree of BMP distribution among and within sub-watersheds. A statistical optimization framework is developed and evaluated in Chaohe River Watershed located in the northern mountain area of Beijing. Results show that BMP implementation significantly (p >0.001) decrease P loss from the watershed. Remedial strategies where BMPs were targeted to areas of high risk of P loss, deceased P loads compared with strategies where BMPs were randomly located across watersheds. Sensitivity analysis indicated that aggregated BMP placement in particular watershed is the most cost-effective scenario to decrease P loss. The optimization approach outlined in this paper is a spatially hierarchical method for targeting nonpoint source controls across a range of scales from field to farm, to watersheds, to regions. Further, model estimates showed targeting at multiple scales is necessary to optimize program efficiency. The integrated model approach described that selects and places BMPs at varying levels of implementation, provides a new theoretical basis and technical guidance for diffuse pollution management in agricultural watersheds.

Humic-like Substances (HULIS) encompass a continuum of molecular weight MW) ranges, yet our understanding of how HULIS characteristics vary with MW limited and not well-established. In this study, a combination of ultrafiltration and solid-phase extraction protocols was employed to fractionate the high MW (HMW, > and low MW (LMW, < 1kDa) HULIS fractions from ambient aerosols collected during summer and winter at a rural site. Subsequently, comprehensive characterization using total organic carbon, high-performance size exclusion chromatography HPSEC), UV-vis and fluorescence spectroscopy, Fourier-transform infrared spectroscopy (FTIR), negative electrospray ionization high resolution mass spectrometry (ESI-HRMS) were conducted. The results revealed that HMW HULIS dominated by larger-sized chromophores, substantially constituting a higher fraction of total organic carbon and UV absorption at 254 nm than LMW HULIS. While HMW and LMW HULIS shared similar fluorophore types and functional groups, former exhibited higher levels of humification and a greater presence of polar functional groups (e.g., -COOH, >C=O). HRMS analysis further unveiled that molecular formulas within HMW HULIS generally featured smaller sizes but higher degrees of unsaturation and aromaticity compared to those within LMW HULIS fractions. This observation suggests the possibility of small molecules assembling form the HMW HULIS through intermolecular weak forces. Moreover, HMW HULIS contained a higher proportion of CHON but fewer CHO compounds than LMW HULIS. In both HMW and LMW HULIS, the unique molecular formulas were primarilycharacterized by lignin-like species, yet the former displayed a prevalence of N40 enriched and highly aromatic species. Additionally, HMW HULIS contained more unique lipids-like compounds, while LMW HULIS exhibited a distinct presence of tannin-like compounds. These findings provide valuable insights into the distribution, optical properties, and molecular-level characteristics of HULIS in atmospheric aerosols, thereby advancing our understanding of their sources, composition, and environmental implications. [ABSTRACT FROM AUTHOR]