Genomic and transcriptomic landscape to decipher the genetic basis of hyperpigmentation in Lanping black-boned sheep (Ovis aries).

BACKGROUND: Lanping black-boned sheep (LPB) represent a distinctive mammalian species characterized by hyperpigmentation, resulting in black bone and muscle features, in contrast to their conventional counterparts exhibiting red muscle and white bone. The genetic basis underlying LPB hyperpigmentation has remained enigmatic. METHODS: In this study, we conducted whole-genome sequencing of 100 LPB and 50 Lanping normal sheep (LPN), and integrated this data with 421 sequenced datasets from wild and domestic sheep, shedding light on the genetic backdrop and genomic variations associated with LPB. Furthermore, we performed comparative RNA-Seq analysis using liver sample to pinpoint genes implicated in the pigmentation process. We generated a comprehensive dataset comprising 97,944,357 SNPs from 571 sheep, facilitating an in-depth exploration of genetic factors. RESULTS: Population genetic structure analysis revealed that the LPB breed traces its origin back to LPN, having evolved into a distinct breed. The integration of positively selected genes with differentially expressed genes identified two candidates, ERBB4 and ROR1, potentially linked to LPB hyperpigmentation. Comparative analysis of ERBB4 and ROR1 mRNA relative expression levels in liver, spleen, and kidney tissues of LPB, in comparison to Diqing sheep, revealed significant upregulation, except for ERBB4 in the liver. Gene expression heatmaps further underscored marked allelic frequency disparities in different populations. CONCLUSION: Our findings establish the evolutionary lineage of the LPB breed from LPN and underscore the involvement of ERBB4 and ROR1 genes in melanin synthesis. These results enhance our comprehension of the molecular basis of hyperpigmentation and contribute to a more comprehensive depiction of sheep diversity.

Genomic and immune heterogeneity of multiple synchronous lung adenocarcinoma at different developmental stages.

Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.

Application of Pan-Omics Technologies in Research on Important Economic Traits for Ruminants.

The economic significance of ruminants in agriculture underscores the need for advanced research methodologies to enhance their traits. This review aims to elucidate the transformative role of pan-omics technologies in ruminant research, focusing on their application in uncovering the genetic mechanisms underlying complex traits such as growth, reproduction, production performance, and rumen function. Pan-omics analysis not only helps in identifying key genes and their regulatory networks associated with important economic traits but also reveals the impact of environmental factors on trait expression. By integrating genomics, epigenomics, transcriptomics, metabolomics, and microbiomics, pan-omics enables a comprehensive analysis of the interplay between genetics and environmental factors, offering a holistic understanding of trait expression. We explore specific examples of economic traits where these technologies have been pivotal, highlighting key genes and regulatory networks identified through pan-omics approaches. Additionally, we trace the historical evolution of each omics field, detailing their progression from foundational discoveries to high-throughput platforms. This review provides a critical synthesis of recent advancements, offering new insights and practical recommendations for the application of pan-omics in the ruminant industry. The broader implications for modern animal husbandry are discussed, emphasizing the potential for these technologies to drive sustainable improvements in ruminant production systems.

Application of GWAS and mGWAS in Livestock and Poultry Breeding.

In recent years, genome-wide association studies (GWAS) and metabolome genome-wide association studies (mGWAS) have emerged as crucial methods for investigating complex traits in animals and plants. These have played pivotal roles in research on livestock and poultry breeding, facilitating a deeper understanding of genetic diversity, the relationship between genes, and genetic bases in livestock and poultry. This article provides a review of the applications of GWAS and mGWAS in animal genetic breeding, aiming to offer reference and inspiration for relevant researchers, promote innovation in animal genetic improvement and breeding methods, and contribute to the sustainable development of animal husbandry.

Beef Cattle Genome Project: Advances in Genome Sequencing, Assembly, and Functional Genes Discovery.

Beef is a major global source of protein, playing an essential role in the human diet. The worldwide production and consumption of beef continue to rise, reflecting a significant trend. However, despite the critical importance of beef cattle resources in agriculture, the diversity of cattle breeds faces severe challenges, with many breeds at risk of extinction. The initiation of the Beef Cattle Genome Project is crucial. By constructing a high-precision functional annotation map of their genome, it becomes possible to analyze the genetic mechanisms underlying important traits in beef cattle, laying a solid foundation for breeding more efficient and productive cattle breeds. This review details advances in genome sequencing and assembly technologies, iterative upgrades of the beef cattle reference genome, and its application in pan-genome research. Additionally, it summarizes relevant studies on the discovery of functional genes associated with key traits in beef cattle, such as growth, meat quality, reproduction, polled traits, disease resistance, and environmental adaptability. Finally, the review explores the potential of telomere-to-telomere (T2T) genome assembly, structural variations (SVs), and multi-omics techniques in future beef cattle genetic breeding. These advancements collectively offer promising avenues for enhancing beef cattle breeding and improving genetic traits.

Exploring the additive effect of Ampelopsis grossedentata flavonoids and Tween 80 on feeding Nubian goats.

Introduction: The ban on antibiotics in animal husbandry underscores the crucial need for safe, natural feed additives. This study investigates the effects of Ampelopsis grossedentata flavonoids (AGF) and Tween 80 on the growth performance, blood indexes, and rumen microbiota of Nubian goats, evaluating their potential as alternative feed additives in livestock management. Methods: Thirty-two goats were randomly divided into four groups. The control group (CON group) was provided with a basal diet, while the experimental groups received diets supplemented with various dietary additives for a duration of 100 days: either a basal diet supplemented with 25 mg/kg of monensin (MN group), a basal diet containing 2.0 g/kg of Ampelopsis grossedentata flavonoids (AGF group), or a basal diet containing 7.5 mL/kg of Tween 80 (TW group). Blood and rumen fluid samples were collected for analysis at the end of the feeding period. Growth performance was monitored through regular weighing and feed intake measurements. Blood indexes were analyzed using standard biochemical techniques, while the microbial composition of the rumen fluid was determined through high throughput 16S rRNA gene sequencing to assess microbial diversity and function. The effects of the dietary treatments on growth performance, blood indexes, and rumen microbial composition were then evaluated. Results: The AGF group exhibited significantly increased average daily gain, and decreased feed-to-gain ratio (p < 0.05). Blood indexes analysis revealed no differences between the CON and AGF groups, with both showing higher concentrations of triglyceride, low-density lipoprotein cholesterol, glutamic-pyruvic transaminase, alkaline phosphatase, and lactate dehydrogenase compared to the monensin group (p < 0.05). The TW group had significantly higher glucose, glutamic-oxaloacetic transaminase, and glutamic-pyruvic transaminase levels than the MN group (p < 0.05). Microbial diversity analysis revealed that the TW group had significantly greater alpha-diversity than other groups, while beta-diversity analysis showed closer similarity between the rumen microbiota of the AGF and CON groups. LEfSe analysis identified Proteobacteria, Deferribacteres, Ehryarchaeoia, and Elusimicrobia as biomarkers distinguishing the rumen microbiota among the groups. In conclusion, AGF supplementation increased the relative abundance of beneficial bacteria in the rumen of Nubian goats, and thus enhanced the growth performance. TW supplementation significantly increased rumen microbial diversity and abundance, suggesting benefits for rumen health despite poor palatability. These findings highlight the potential of AGF as a new green additive with important implications for the efficiency and development of animal husbandry.

Comprehensive analysis of college students' autonomous fitness behavior-a narrative review.

Although the physical health of college students is increasingly receiving attention, their autonomous fitness behavior has not been thoroughly investigated. This narrative review conducted a comprehensive literature search through databases such as PubMed, PsycINFO, Web of Science, and the China National Knowledge Infrastructure (CNKI), reviewing studies published up to December 2023. We explored the constructs of autonomy, fitness behavior, and agency, and discussed their integration within the autonomous fitness model. Our findings indicate a lack of comprehensive studies exploring the multifaceted factors influencing autonomous fitness behaviors. Future research should strive to deepen conceptual understanding and further explore the complex dynamics of the transition from autonomy to persistence, employing technological and interdisciplinary methodological perspectives to enhance understanding and promote sustainable fitness habits.

Transcriptomic annotation of the Chungtien schizothoracin (Ptychobarbus chungtienensis) using Iso-seq and RNA-seq data.

The Chungtien schizothoracin (Ptychobarbus chungtienensis), an endangered fish species endemic to the Zhongdian Plateau, remains underexplored in terms of transcriptomic sequencing. This investigation used tissues from five distinct organs (heart, liver, spleen, kidney, and brain) of the Chungtien schizothoracin for PacBio Iso-seq and RNA-seq analyses, yielding a repertoire of 16,598 full-length transcripts spanning lengths from 363 bp to 7,157 bp. Gene family clustering and phylogenetic analysis encompassed a comprehensive set of 13 fish species, all of which were cyprinids, including the zebrafish and the examined species Ptychobarbus chungtienensis. Moreover, the identification of long non-coding RNAs (lncRNAs) and coding sequences was accomplished across all five tissues. Comprehensive analyses of gene expression profiles and differentially expressed genes among the above five tissues were performed. In summary, the obtained full-length transcripts and detailed gene expression profiles of the Chungtien schizothoracin tissues furnish crucial expression data and genetic sequences, laying the groundwork for future investigations and fostering a holistic comprehension of the adaptive mechanisms inherent in the Chungtien schizothoracin under various conditions.

Evolutionary proteogenomic landscape from pre-invasive to invasive lung adenocarcinoma.

Lung adenocarcinoma follows a stepwise progression from pre-invasive to invasive. However, there remains a knowledge gap regarding molecular events from pre-invasive to invasive. Here, we conduct a comprehensive proteogenomic analysis comprising whole-exon sequencing, RNA sequencing, and proteomic and phosphoproteomic profiling on 98 pre-invasive and 99 invasive lung adenocarcinomas. The deletion of chr4q12 contributes to the progression from pre-invasive to invasive adenocarcinoma by downregulating SPATA18, thus suppressing mitophagy and promoting cell invasion. Proteomics reveals diverse enriched pathways in normal lung tissues and pre-invasive and invasive adenocarcinoma. Proteomic analyses identify three proteomic subtypes, which represent different stages of tumor progression. We also illustrate the molecular characterization of four immune clusters, including endothelial cells, B cells, DCs, and immune depression subtype. In conclusion, this comprehensive proteogenomic study characterizes the molecular architecture and hallmarks from pre-invasive to invasive lung adenocarcinoma, guiding the way to a deeper understanding of the tumorigenesis and progression of this disease.

Pan-Omics in Sheep: Unveiling Genetic Landscapes.

Multi-omics-integrated analysis, known as panomics, represents an advanced methodology that harnesses various high-throughput technologies encompassing genomics, epigenomics, transcriptomics, proteomics, and metabolomics. Sheep, playing a pivotal role in agricultural sectors due to their substantial economic importance, have witnessed remarkable advancements in genetic breeding through the amalgamation of multiomics analyses, particularly with the evolution of high-throughput technologies. This integrative approach has established a robust theoretical foundation, enabling a deeper understanding of sheep genetics and fostering improvements in breeding strategies. The comprehensive insights obtained through this approach shed light on diverse facets of sheep development, including growth, reproduction, disease resistance, and the quality of livestock products. This review primarily focuses on the application of principal omics analysis technologies in sheep, emphasizing correlation studies between multiomics data and specific traits such as meat quality, wool characteristics, and reproductive features. Additionally, this paper anticipates forthcoming trends and potential developments in this field.

Unveiling the common loci for six body measurement traits in Chinese Wenshan cattle.

Introduction: Body measurement traits are integral in cattle production, serving as pivotal criteria for breeding selection. Wenshan cattle, a local breed in China's Yunnan province, exhibit remarkable genetic diversity. However, the molecular mechanisms regulating body measurement traits in Wenshan cattle remain unexplored. Methods: In this study, we performed a genome-wide association method to identify genetic architecture for body height body length hip height back height (BAH), waist height and ischial tuberosity height using the Bovine 50 K single nucleotide polymorphism Array in 1060 Wenshan cattles. Results: This analysis reveals 8 significant SNPs identified through the mixed linear model (MLM), with 6 SNPs are associated with multiple traits and 4 SNPs are associated with all 6 traits. Furthermore, we pinpoint 21 candidate genes located in proximity to or within these significant SNPs. Among them, Scarb1, acetoacetyl-CoA synthetase and HIVEP3 were implicated in bone formation and rarely encountered in livestock body measurement traits, emerge as potential candidate genes regulating body measurement traits in Wenshan cattle. Discussion: This investigation provides valuable insights into the genetic mechanisms underpinning body measurement traits in this unique cattle breed, paving the way for further research in this domain.

Two High-Quality Cygnus Genome Assemblies Reveal Genomic Variations Associated with Plumage Color.

As an exemplary model for examining molecular mechanisms responsible for extreme phenotypic variations, plumage color has garnered significant interest. The Cygnus genus features two species, Cygnus olor and Cygnus atratus, that exhibit striking disparities in plumage color. However, the molecular foundation for this differentiation has remained elusive. Herein, we present two high-quality genomes for C. olor and C. atratus, procured using the Illumina and Nanopore technologies. The assembled genome of C. olor was 1.12 Gb in size with a contig N50 of 26.82 Mb, while its counterpart was 1.13 Gb in size with a contig N50 of 21.91 Mb. A comparative analysis unveiled three genes (TYR, SLC45A2, and SLC7A11) with structural variants in the melanogenic pathway. Notably, we also identified a novel gene, PWWP domain containing 2A (PWWP2A), that is related to plumage color, for the first time. Using targeted gene modification analysis, we demonstrated the potential genetic effect of the PWWP2A variant on pigment gene expression and melanin production. Finally, our findings offer insight into the intricate pattern of pigmentation and the role of polygenes in birds. Furthermore, these two high-quality genome references provide a comprehensive resource and perspective for comparative functional and genetic studies of evolution within the Cygnus genus.

Residual tumor descriptors proposed by the International Association for the Study of Lung Cancer may not be applicable to stage I and ground-glass opacity-featured non-small cell lung cancer.

Background: The International Association for the Study of Lung Cancer (IASLC) has proposed a residual tumor descriptor, essential for subsequent treatments. This study aimed to validate the prognostic effect of the proposed R descriptor and restrict its scope of clinical application in a large-scale cohort with non-small cell lung cancer (NSCLC). Methods: Patients, who underwent lobectomy from January 2010 to May 2019, were retrospectively reviewed. Patients were categorized according to the different R classification standards proposed by Union for International Cancer Control (UICC) and IASLC. Results: Among 5,200 enrolled patients with NSCLC, 1,727 and 9 cases of UICC-R0 were re-evaluated as uncertain resection [R(un)] and R1, respectively. After reclassification, there were 3,228 (62.1%) cases of R0, 1,727 (33.2%) cases of R(un), 151 (2.9%) cases of R1, and 94 (1.8%) cases of R2. Not performing rigorous systematic nodal dissection (SND) or lobe-specific SND (68.3%) was the main reason for the alteration from R0 to R(un). Patients with R(un) showed intermediate survival between those with R0 and R1. Further multivariable Cox analysis indicated that the proposed R descriptor was an independent prognostic factor for overall survival (OS) and recurrence-free survival (RFS). However, subgroup analysis of OS and RFS revealed that there was no significant difference between R0 and R(un) in patients with ground-glass opacity (GGO) or patients with tumor-node-metastasis stage I. Conclusions: R(un) represented an intermediate type between R0 and R1. Our study provided an external validation for new residual tumor descriptors for NSCLC proposed by IASLC. Proposed residual tumor descriptors were applicable in radiologic solid NSCLC and stage II-III NSCLC, but were ineffective for GGO-featured or stage I NSCLC.

Molecular Cloning and Functional Characterization of the 5' Regulatory Region of the SLC11A1 Gene from Yaks.

The solute transport protein family 11 A1 (SLC11A1), also recognized as natural resistance-associated macrophage protein 1 (NRAMP1), represents a transmembrane protein encoded by the SLC11A1 gene. A variety of prior investigations have illuminated its involvement in conferring resistance or susceptibility to bacterial agents, positioning it as a promising candidate gene for breeding disease-resistant animals. Yaks (Bos grunniens), renowned inhabitants of the Qinghai-Tibet Plateau in China, stand as robust ruminants distinguished by their adaptability and formidable disease resistance. Notwithstanding these unique traits, there is scant literature on the SLC11A1 gene in the yak population. Our inquiry commences with the cloning of the 5' regulatory region sequence of the Zhongdian yak SLC11A1 gene. We employ bioinformatics tools to identify transcription factor binding sites, delineating pivotal elements like enhancers and cis-acting elements. To ascertain the promoter activity of this region, we amplify four distinct promoter fragments within the 5' regulatory region of the yak SLC11A1 gene. Subsequently, we design a luciferase reporter gene vector containing four site-specific deletion mutations and perform transient transfection experiments. Through these experiments, we measure and compare the activity of disparate gene fragments located within the 5' regulatory region, revealing regions bearing promoter functionality and discerning key regulatory elements. Our findings validate the promoter functionality of the 5' regulatory region, offering preliminary insights into the core and principal regulatory segments of this promoter. Notably, we identified single nucleotide polymorphisms (SNPs) that may be associated with important regulatory elements such as NF-1 and NF-1/L. This study provides a theoretical framework for in-depth research on the function and expression regulation mechanism of the yak SLC11A1 gene.

Elevated Mast Cell Abundance Is Associated with Enrichment of CCR2+ Cytotoxic T Cells and Favorable Prognosis in Lung Adenocarcinoma.

Mast cells constitute indispensable immunoregulatory sentinel cells in the tumor microenvironment. A better understanding of the regulation and functions of mast cells in lung adenocarcinoma (LUAD) could uncover therapeutic approaches to reprogram the immunosuppressive tumor microenvironment. Here, we performed flow cytometry and single-cell RNA sequencing (scRNA-seq) of patient LUAD samples to comprehensively characterize LUAD-infiltrating mast cells. Mast cells exhibited functional heterogeneity and were enriched in LUAD with ground-glass opacity features (gLUAD). The mast cells in gLUAD exhibited proinflammatory and chemotactic properties while those in radiologically solid LUAD (sLUAD) were associated with tumor angiogenesis. Mast cells were an important source of CCL2 and correlated with the recruitment of CCR2+ CTL, a specific subcluster of preexhausted T cells with tissue-resident memory phenotype and enhanced cytotoxicity. Increased infiltration of mast cells and CCR2+ CTLs and their colocalization showed a strong association with favorable prognosis after surgery but were not associated with improved survival after chemotherapy. Collectively, these findings reveal a key role of mast cells in LUAD and their potential cross-talk with CTLs, suggesting that targeting mast cells may be an immunotherapeutic strategy for LUAD. SIGNIFICANCE: Comprehensive characterization of mast cells in lung adenocarcinoma elucidates their heterogeneity and identifies interplay between mast cells and CCR2+ T cells that is associated with a favorable prognosis.

Identification of Germline Mutations in East-Asian Young Never-Smokers with Lung Adenocarcinoma by Whole-Exome Sequencing.

Recently, an increasing number of young never-smokers are diagnosed with lung cancer. The aim of this study is to investigate the genetic predisposition of lung cancer in these patients and discover candidate pathogenic variants for lung adenocarcinoma in young never-smokers. Peripheral blood was collected from 123 never-smoking east-Asian patients diagnosed with lung adenocarcinoma before the age of 40. Whole-exome sequencing (WES) was conducted on genomic DNA extracted from peripheral blood cells. As a result, 3,481 single nucleotide variants were identified. By bioinformatical tools and the published gene list associated with genetic predisposition of cancer, pathogenic variants were detected in ten germline genes: ATR, FANCD2, FANCE, GATA2, HFE, MSH2, PDGFRA, PMS2, SDHB, and WAS. Patients with pathogenic variants were more likely to occur in females (9/10, 90.0%) and have stage IV lung adenocarcinoma (4/10, 40%). Furthermore, germline mutations in 17 genes (ASB18, B3GALT5, CLEC4F, COL6A6, CYP4B1, C6orf132, EXO1, GATA4, HCK, KCP, NPHP4, PIGX, PPIL2, PPP1R3G, RRBP1, SALL4, and TTC28), which occurred in at least two patients, displayed potentially pathogenic effects. Gene ontology analysis further showed that these genes with germline mutations were mainly located in nucleoplasm and associated with DNA repair-related biological processes. The study provides spectrum of pathogenic variants and functional explanation for genetic predisposition of lung adenocarcinoma in young never-smokers, which sheds a light on prevention and early diagnosis of lung cancer. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-022-00062-1.

A look under the hood of genomic-estimated breed compositions for brangus cattle: What have we learned?

The Brangus cattle were developed to utilize the superior traits of Angus and Brahman cattle. Their genetic compositions are expected to be stabilized at 3/8 Brahman and 5/8 Angus. Previous studies have shown more than expected Angus lineage with Brangus cattle, and the reasons are yet to be investigated. In this study, we revisited the breed compositions for 3,605 Brangus cattle from three perspectives: genome-wise (GBC), per chromosomes (CBC), and per chromosome segments (SBC). The former (GBC) depicted an overall picture of the "mosaic" genome of the Brangus attributable to their ancestors, whereas the latter two criteria (CBC and SBC) corresponded to local ancestral contributions. The average GBC for the 3,605 Brangus cattle were 70.2% Angus and 29.8% Brahman. The K-means clustering supported the postulation of the mixture of 1/2 Ultrablack (UB) animals in Brangus. For the non-UB Brangus animals, the average GBC were estimated to be 67.4% Angus and 32.6% Brahman. The 95% confidence intervals of their overall GBC were 60.4%-73.5% Angus and 26.5%-39.6% Brahman. Possibly, genetic selection and drifting have resulted in an approximately 5% average deviation toward Angus lineage. The estimated ancestral contributions by chromosomes were heavily distributed toward Angus, with 27 chromosomes having an average Angus CBC greater than 62.5% but only two chromosomes (5 and 20) having Brahman CBC greater than 37.5%. The chromosomal regions with high Angus breed proportions were prevalent, tending to form larger blocks on most chromosomes. In contrast, chromosome segments with high Brahman breed proportion were relatively few and isolated, presenting only on seven chromosomes. Hence, genomic hitchhiking effects were strong where Angus favorable alleles resided but weak where Brahman favorable alleles were present. The functions of genes identified in the chromosomal regions with high ( ≥ 75 % ) Angus compositions were diverse yet may were related to growth and body development. In contrast, the genes identified in the regions with high ( ≥ 37.5 % ) Brahman compositions were primarily responsible for disease resistance. In conclusion, we have addressed the questions concerning the Brangus genetic make-ups. The results can help form a dynamic picture of the Brangus breed formation and the genomic reshaping.

The role of parents in the motivation of young athletes: a systematic review.

Objectives: Parents are one of the main social agents that shape young athletes' experiences and participation in sports, but they are also the least explored group in the literature. Therefore, the purpose of this study was to conduct a systematic review of research on the role of parents in the motivation of young athletes. Method: The systematic literature review consisted of four electronic databases from which 29 articles published in English and in full-text form in peer-reviewed journals between 1999 and 2023 were retrieved. Results: A total of 29 studies met the eligibility criteria. These studies collectively surveyed 9,185 young athlete participants and 2,191 parent participants. The sample comprised 26 quantitative studies and 3 qualitative studies. The findings underscore that parents play both unique and synergistic multidimensional roles in motivating young athletes. Parents' positive goals and values, autonomy-supportive parenting styles, moderate parental involvement, positive parent-child relationships, and a parent-initiated task climate are identified as optimal parenting strategies. Conclusion: While parents undeniably play a crucial role in motivating young athletes, the manner and extent of their involvement are key.

Image Segmentation of Retinal Blood Vessels Based on Dual-Attention Multiscale Feature Fusion.

Aiming at the problem of insufficient details of retinal blood vessel segmentation in current research methods, this paper proposes a multiscale feature fusion residual network based on dual attention. Specifically, a feature fusion residual module with adaptive calibration weight features is designed, which avoids gradient dispersion and network degradation while effectively extracting image details. The SA module and ECA module are used many times in the backbone feature extraction network to adaptively select the focus position to generate more discriminative feature representations; at the same time, the information of different levels of the network is fused, and long-range and short-range features are used. This method aggregates low-level and high-level feature information, which effectively improves the segmentation performance. The experimental results show that the method in this paper achieves the classification accuracy of 0.9795 and 0.9785 on the STARE and DRIVE datasets, respectively, and the classification performance is better than the current mainstream methods.

Increased Tumor Intrinsic Growth Potential and Decreased Immune Function Orchestrate the Progression of Lung Adenocarcinoma.

Background: The overall 5-year survival of lung cancer was reported to be only ~15%, with lung adenocarcinoma (LUAD) as the main pathological subtype. Before developing into invasive stages, LUAD undergoes pre-invasive stages of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), where surgical resection gives an excellent 5-year survival rate. Given the dramatic decline of prognosis from pre-invasive to invasive stages, a deeper understanding of key molecular changes driving the progression of LUAD is highly needed. Methods: In this study, we performed whole-exome sequencing and RNA sequencing on surgically resected 24 AIS, 74 MIA, 99 LUAD specimens, and their adjacent paired normal tissues. Survival data were obtained by follow-up after surgery. Key molecular events were found by comparing the gene expression profiles of tumors with different stages. Finally, to measure the level of imbalance between tumor intrinsic growth potential and immune microenvironment, a tumor progressive (TP) index was developed to predict tumor progression and patients' survival outcome and validated by external datasets. Results: As tumors progressed to more invasive stages, they acquired higher growth potential, mutational frequency of tumor suppressor genes, somatic copy number alterations, and tumor mutation burden, along with suppressed immune function. To better predict tumor progression and patients' outcome, TP index were built to measure the imbalance between tumor intrinsic growth potential and immune microenvironment. Patients with a higher TP index had significantly worse recurrence-free survival [Hazard ratio (HR), 10.47; 95% CI, 3.21-34.14; p < 0.0001] and overall survival (OS) [Hazard ratio (HR), 4.83e8; 95% CI, 0-Inf; p = 0.0013]. We used The Cancer Genome Atlas (TCGA)-LUAD dataset for validation and found that patients with a higher TP index had significantly worse OS (HR, 1.10; 95% CI, 0.83-1.45; p = 0.048), demonstrating the prognostic value of the TP index for patients with LUAD. Conclusions: The imbalance of tumor intrinsic growth potential and immune function orchestrate the progression of LUAD, which can be measured by TP index. Our study provided new insights into predicting survival of patients with LUAD and new target discovery for LUAD through assessing the imbalance between tumor intrinsic growth potential and immune function.