Time series study on the effect of low air pollution level NO2 On the death of residents from cardiovascular and cerebrovascular diseases

Objective: To explore the impact of low-level atmospheric nitrogen dioxide (NO2) on the death risk of cardiovascular and cerebrovascular diseases in Enshi City, so as to provide scientific basis for locating sensitive populations and formulating population health policiesmethods the monitoring of air pollutants, meteorological factors and death data of residents from cardiovascular and cerebrovascular diseases in Enshi City from 2015 to 2018 were collected. The generalized additive model based on Poisson distribution was used to analyze the impact of low air pollution level NO2 on the death risk of cardiovascular and cerebrovascular diseases in Enshi City, and subgroup analysis was carried out on age, gender and seasonresults the average concentrations of major gaseous pollutants in Enshi from 2015 to 2018 were NO2 (21.40 μg/m3), sulfur dioxide (so, 9.68 μg/m3). Carbon oxide (CO, 0.88 mg/m3) and ozone (O, 61.21 μg/m3). The results of single pollutant model analysis show that every increase of NO2 concentration in the total population μg/m, the risk of death from cardiovascular and cerebrovascular diseases on the same day (lag0) will increase by 0.33% (-0.06%~0.72%) (P>0.05); In the female population, every 1% increase in NO2 concentration μg/m, the death risk of cardiovascular and cerebrovascular diseases with cumulative lag of 1 day (lag01) will increase by 0.92% (0.26%~1.56%) (P < 0.05); In the cold season, every increase of NO2 concentration μg/m, the death risk of cardiovascular and cerebrovascular diseases in the whole population on the same day (lag0) will increase by 0.62% (0.12%~1.12%) (P < 0.05). The results of the two pollutant model show that after controlling other gaseous pollutants (SO2, Co or O3), the impact of NO2 on the death risk of cardiovascular and cerebrovascular diseases in women and the whole population in cold season still exists. Conclusion: Low pollution level of NO2 in Enshi City will increase the death risk of cardiovascular and cerebrovascular diseases among women and the whole population in cold season. Attention should be paid to the health protection of special populations in low pollution areas and in special seasons

YOLOv8-Peas: a lightweight drought tolerance method for peas based on seed germination vigor

IntroductionDrought stress has become an important factor affecting global food production. Screening and breeding new varieties of peas (Pisum sativum L.) for drought-tolerant is of critical importance to ensure sustainable agricultural production and global food security. Germination rate and germination index are important indicators of seed germination vigor, and the level of germination vigor of pea seeds directly affects their yield and quality. The traditional manual germination detection can hardly meet the demand of full-time sequence nondestructive detection. We propose YOLOv8-Peas, an improved YOLOv8-n based method for the detection of pea germination vigor.MethodsWe constructed a pea germination dataset and used multiple data augmentation methods to improve the robustness of the model in real-world scenarios. By introducing the C2f-Ghost structure and depth-separable convolution, the model computational complexity is reduced and the model size is compressed. In addition, the original detector head is replaced by the self-designed PDetect detector head, which significantly improves the computational efficiency of the model. The Coordinate Attention (CA) mechanism is added to the backbone network to enhance the model's ability to localize and extract features from critical regions. The neck used a lightweight Content-Aware ReAssembly of FEatures (CARAFE) upsampling operator to capture and retain detailed features at low levels. The Adam optimizer is used to improve the model's learning ability in complex parameter spaces, thus improving the model's detection performance.ResultsThe experimental results showed that the Params, FLOPs, and Weight Size of YOLOv8-Peas were 1.17M, 3.2G, and 2.7MB, respectively, which decreased by 61.2%, 61%, and 56.5% compared with the original YOLOv8-n. The mAP of YOLOv8-Peas was on par with that of YOLOv8-n, reaching 98.7%, and achieved a detection speed of 116.2FPS. We used PEG6000 to simulate different drought environments and YOLOv8-Peas to analyze and quantify the germination vigor of different genotypes of peas, and screened for the best drought-resistant pea varieties.DiscussionOur model effectively reduces deployment costs, improves detection efficiency, and provides a scientific theoretical basis for drought-resistant genotype screening in pea

Comparison of variations detection between whole-genome amplification methods used in single-cell resequencing

Background: Single-cell resequencing (SCRS) provides many biomedical advances in variations detection at the single-cell level, but it currently relies on whole genome amplification (WGA). Three methods are commonly used for WGA: multiple displacement amplification (MDA), degenerate-oligonucleotide-primed PCR (DOP-PCR) and multiple annealing and looping-based amplification cycles (MALBAC). However, a comprehensive comparison of variations detection performance between these WGA methods has not yet been performed. Results: We systematically compared the advantages and disadvantages of different WGA methods, focusing particularly on variations detection. Low-coverage whole-genome sequencing revealed that DOP-PCR had the highest duplication ratio, but an even read distribution and the best reproducibility and accuracy for detection of copy-number variations (CNVs). However, MDA had significantly higher genome recovery sensitivity (~84 %) than DOP-PCR (~6 %) and MALBAC (~52 %) at high sequencing depth. MALBAC and MDA had comparable single-nucleotide variations detection efficiency, false-positive ratio, and allele drop-out ratio. We further demonstrated that SCRS data amplified by either MDA or MALBAC from a gastric cancer cell line could accurately detect gastric cancer CNVs with comparable sensitivity and specificity, including amplifications of 12p11.22 (KRAS) and 9p24.1 (JAK2, CD274, and PDCD1LG2). Conclusions: Our findings provide a comprehensive comparison of variations detection performance using SCRS amplified by different WGA methods. It will guide researchers to determine which WGA method is best suited to individual experimental needs at single-cell level

Whole exome sequencing identifies frequent somatic mutations in cell-cell adhesion genes in chinese patients with lung squamous cell carcinoma

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy

Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets

Integrated Profiling of MicroRNAs and mRNAs: MicroRNAs Located on Xq27.3 Associate with Clear Cell Renal Cell Carcinoma

Background: With the advent of second-generation sequencing, the expression of gene transcripts can be digitally measured with high accuracy. The purpose of this study was to systematically profile the expression of both mRNA and miRNA genes in clear cell renal cell carcinoma (ccRCC) using massively parallel sequencing technology. Methodology: The expression of mRNAs and miRNAs were analyzed in tumor tissues and matched normal adjacent tissues obtained from 10 ccRCC patients without distant metastases. In a prevalence screen, some of the most interesting results were validated in a large cohort of ccRCC patients. Principal Findings: A total of 404 miRNAs and 9,799 mRNAs were detected to be differentially expressed in the 10 ccRCC patients. We also identified 56 novel miRNA candidates in at least two samples. In addition to confirming that canonical cancer genes and miRNAs (including VEGFA, DUSP9 and ERBB4; miR-210, miR-184 and miR-206) play pivotal roles in ccRCC development, promising novel candidates (such as PNCK and miR-122) without previous annotation in ccRCC carcinogenesis were also discovered in this study. Pathways controlling cell fates (e. g., cell cycle and apoptosis pathways) and cell communication (e. g., focal adhesion and ECM-receptor interaction) were found to be significantly more likely to be disrupted in ccRCC. Additionally, the results of the prevalence screen revealed that the expression of a miRNA gene cluster located on Xq27.3 was consistently downregulated in at least 76.7% of similar to 50 ccRCC patients. Conclusions: Our study provided a two-dimensional map of the mRNA and miRNA expression profiles of ccRCC using deep sequencing technology. Our results indicate that the phenotypic status of ccRCC is characterized by a loss of normal renal function, downregulation of metabolic genes, and upregulation of many signal transduction genes in key pathways. Furthermore, it can be concluded that downregulation of miRNA genes clustered on Xq27.3 is associated with ccRCC

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexit