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Rationale: Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by airway obstruction and accelerated lung function decline. Our understanding of systemic protein biomarkers associated with COPD remains incomplete. Objectives: To determine what proteins and pathways are associated with impaired pulmonary function in a diverse population. Methods: We studied 6,722 participants across six cohort studies with both aptamer-based proteomic and spirometry data (4,566 predominantly White participants in a discovery analysis and 2,156 African American cohort participants in a validation). In linear regression models, we examined protein associations with baseline forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC). In linear mixed effects models, we investigated the associations of baseline protein levels with rate of FEV1 decline (ml/yr) in 2,777 participants with up to 7 years of follow-up spirometry. Results: We identified 254 proteins associated with FEV1 in our discovery analyses, with 80 proteins validated in the Jackson Heart Study. Novel validated protein associations include kallistatin serine protease inhibitor, growth differentiation factor 2, and tumor necrosis factor-like weak inducer of apoptosis (discovery β = 0.0561, Q = 4.05 × 10-10; β  = 0.0421, Q = 1.12 × 10-3; and β = 0.0358, Q = 1.67 × 10-3, respectively). In longitudinal analyses within cohorts with follow-up spirometry, we identified 15 proteins associated with FEV1 decline (Q

Background Coronary heart disease (CHD) is the leading cause of death world wide. Coronary angiography is often used as an effective approach for the diagnosis of CHD. However, coronary angiography accounts for relatively low percentagein examination approaches due to the limitation of various conditions in primary care, and more meaningful biomarkers need to be explored to provide a basis for primary care physicians to diagnose and treat CHD. In the previous study of our research group, it is found that early growth response 3 (Egr3) gene may be a susceptibility factor in the heterogeneity of CHD pathogenesis, and there are few reports on the correlation between CHD and Egr3 gene and inflammatory biomarkers. Objective To investigate the correlation between Egr3, interleukin-6 (IL-6) and CHD, as well as their expression levels and the severity of coronary stenosis, so as to provide a favorable laboratory basis for clinical diagnosis and treatment inprimary care. Methods A total of 110 patients who admitted to the Fifth Affiliated Hospital of Xinjiang Medical University for CHD symptoms and completed coronary artery angiography (CAG) during June to December 2021 were collected and divided into the mild stenosis group (group A≤52 points, n=50) , moderate-severe stenosis group (group B>52 points, n=30) and control group (group C, n=30) according to the CAG results and median Gensini score (52 points) . Serum Egr3 and IL-6 levels of the included patients were measured by enzyme-linked immunosorbent assay. Results The IL-6 level in group B was higher than that in group A and group C (P

Chronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We identify at genome-wide significance 10 known GWAS loci and 22 distinct, previously unreported loci, including two common variant signals from stratified analysis of African Americans. Four novel common variants within the regions of PIAS1, RGN (two variants) and FTO show evidence of replication in the UK Biobank (European ancestry n ~ 320,000), while colocalization analyses leveraging multi-omic data from GTEx and TOPMed identify potential molecular mechanisms underlying four of the 22 novel loci. Our study demonstrates the value of performing WGS analyses and multi-omic follow-up in cohorts of diverse ancestry.

Establishing lucerne field is an efficient way to protect natural steppes, alleviate conflicts between meadows and livestock, and promote the development of animal husbandry. However, problems such as extensive field management, valuing yield over quality, and low resource utilization are endemic in production. Exploring reasonable cultivation patterns can contribute to improving the current situation of artificial grassland production and promoting the high-quality development of husbandry and prataculture. Lucerne the field experiment was carried out in Jingtai, Gansu Province, China in 2021–2022; this study compared and analyzed the effects of three cultivation patterns—ridge tillage with plastic film mulching (PM), ridge tillage with biodegradable film mulching (BM), and traditional flat planting (FP)—on soil water, heat, and fertilizer, as well as lucerne growth, yield, quality, and water and nitrogen use efficiency. The results show that: (1) during the growth period of lucerne, PM and BM treatments augment the average moisture content of the soil layer of 0–120 cm by 31.19% and 24.03% compared to the FP treatment, respectively. In the soil layer of 0–40 cm, PM and BM treatments abate the soil moisture content of the ridges by an average of 19.29% and 7.89% compared to that in the ditches, respectively. In the soil layer of 40–120 cm, PM and BM treatments elevate the soil moisture content of the ridges by 4.40% and 4.65% on average compared to that in the ditches, respectively. The average soil temperature in a soil layer of 5–25 cm shows PM > BM > FP. In contrast with the FP treatment, PM and BM treatments increase the soil temperature of the ridges by an average of 1.87 °C and 0.96 °C and decrease that of the ditches by an average of 0.47 °C and 0.46 °C, respectively. After two years of planting, the three cultivation patterns all promote the soil nutrient content. Compared to the FP treatment, PM and BM treatments increase the organic matter content by 9.94% and 19.94%, respectively. (2) Ridge tillage with film mulching can evidently stimulate the growth of lucerne and enhance yield and quality. Compared to the FP treatment, PM and BM treatments enhance plant height by an average of 15.37% and 4.04%, stem diameter by an average of 34.14% and 14.58%, yield by an average of 21.20% and 14.77%, crude protein content by an average of 13.47% and 7.68%, and relative feed value by an average of 8.71% and 4.41%, respectively. (3) During the two-year growing period, the irrigation amount of lucerne was 508.60–615.30 mm, and the evapotranspiration was 563.70–761.80 mm. Compared to the FP treatment, PM and BM treatments hoist water use efficiency by an average of 43.50% and 17.56%, nitrogen partial factor productivity by an average of 21.20% and 15.22%, and net income by an average of 14.78% and 11.05%, respectively. In summary, in ridge tillage, both ordinary film mulching and biodegradable film mulching can create a favorable soil environment for lucerne growth and heighten production effect. The former has a better effect on advancing the lucerne production effect, and the latter exhibits superior performance in improving soil fertility. [ABSTRACT FROM AUTHOR]

Smyd1/Bop is an evolutionary conserved histone methyltransferase previously shown by conventional knockout to be critical for embryonic heart development. To further explore the mechanism(s) in a cell autonomous context, we conditionally ablated Smyd1 in the first and second heart fields of mice using a knock-in (KI) Nkx2.5-cre driver. Robust deletion of floxed-Smyd1 in cardiomyocytes and the outflow tract (OFT) resulted in embryonic lethality at E9.5, truncation of the OFT and right ventricle, and additional defects consistent with impaired expansion and proliferation of the second heart field (SHF). Using a transgenic (Tg) Nkx2.5-cre driver previously shown to not delete in the SHF and OFT, early embryonic lethality was bypassed and both ventricular chambers were formed; however, reduced cardiomyocyte proliferation and other heart defects resulted in later embryonic death at E11.5-12.5. Proliferative impairment prior to both early and mid-gestational lethality was accompanied by dysregulation of transcripts critical for endoplasmic reticulum (ER) stress. Mid-gestational death was also associated with impairment of oxidative stress defense-a phenotype highly similar to the previously characterized knockout of the Smyd1-interacting transcription factor, skNAC. We describe a potential feedback mechanism in which the stress response factor Tribbles3/TRB3, when directly methylated by Smyd1, acts as a co-repressor of Smyd1-mediated transcription. Our findings suggest that Smyd1 is required for maintaining cardiomyocyte proliferation at minimally two different embryonic heart developmental stages, and its loss leads to linked stress responses that signal ensuing lethality.