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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.

The impact of the intercropping system on the soil–plant–atmosphere continuum (SPAC), encompassing soil evaporation, soil moisture dynamics, and crop transpiration, remains an area of uncertainty. Field experiments were conducted for two years in conjunction with the SIMDualKc (Simulation Dual Crop Coefficient) model to simulate two planting configurations: sole-cropped wolfberry (Lycium barbarum L.) (D) and wolfberry intercropped with alfalfa (Medicago sativa L.) (J). These configurations were subjected to different irrigation levels: full irrigation (W1, 75–85% θfc), mild deficit irrigation (W2, 65–75% θfc), moderate deficit irrigation (W3, 55–65% θfc), and severe deficit irrigation (W4, 45–55% θfc). The findings revealed that the JW1 treatment reduced the annual average soil evaporation by 32% compared with that of DW1. Additionally, mild, moderate, and severe deficit irrigation reduced soil evaporation by 17, 24, and 36%, respectively, compared with full irrigation. The intercropping system exhibited a more efficient canopy structure, resulting in reduced soil evaporation and alleviation of water stress to a certain extent. In terms of temporal dynamics, monocropping resulted in soil moisture levels from 1% to 15% higher than intercropping, with the most significant differences manifesting in the mid to late stages, whereas differences in the early stages were not statistically significant. Spatially, the intercropping system exhibited 7–19% lower soil water contents (SWCs) than sole cropping, primarily within the root water uptake zone within the 0–60 cm soil layer. The intercropping system showed an enhanced water absorption capacity for plant transpiration, resulting in a 29% increase in transpiration compared with sole cropping, thereby achieving water-saving benefits. These findings contribute to our understanding of the agronomic and environmental implications of intercropping wolfberry and alfalfa in arid regions and provide insights into optimizing water and soil resource management for sustainable agricultural practices. [ABSTRACT FROM AUTHOR]

Co2Z is a planar ferrite, particularly suitable for soft magnetic applications. There is currently a lack of in-depth research on its high-frequency properties. La3+ ion is a potential ion to regulate its magnetism. Based on this, the crystal structure, microstructure, static, and dynamic magnetic properties of Ba3−xLaxCo2Fe24O41 (x = 0.0, 0.05, 0.1, 0.15, 0.2, and 0.25) ceramics were investigated. The findings demonstrate that La substitution retains the crystal structure and form, yet the introduction of extra charge leads to the formation of Fe2+ ions, resulting in a slight decrease in magnetic moment from 51.9 to 48.9 emu/g, while a notable increase in the out-of-plane anisotropic field from 12.2 to 18.3 kOe, which significantly impacts the high-frequency complex magnetic permeability spectrum. Additionally, a thorough analysis of the high-frequency magnetic spectrum indicates that both domain wall movement and magnetization rotation contribute to the magnetic permeability, with magnetization rotation playing predominant. Particularly exciting is that the high-frequency magnetic spectrum results show that the substitution of La for Ba considerably raises the resonance frequency from 2.41 to 3.30 GHz that can be attributed to the increased anisotropy. In conclusion, the substitution of La markedly enhances the high-frequency magnetic properties of Co2Z. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the molecular mechanisms of Huangqi {Astragalus) in the treatment of premature ovarian insufficiency (POI) using network pharmacology and molecular docking methods. Methods: The active compounds and target proteins of Huangqi were screened from the TCMSP database, while the disease target proteins associated with POI were obtained from the Genecards database. The Venny online tool was used to identify the overlapping genes between the two datasets. Cytoscape software was used to construct a gene regulatory network for the active ingredients of Huangqi. The protein-protein interaction (PPI) network and core genes were selected based on the STRING database and CytoNCA plug-in of Cytoscape. GO (gene ontology) enrichment and KEGG (Kyoto encyclopedia of genes and genomes) pathway enrichment analyses of the overlapping genes were performed using the DAVID database. Molecular docking techniques were used to further elucidate the molecular mechanisms underlying the therapeutic effects. Human ovarian granulosa-like tumor cells (KGN) underwent serum starvation (SS) treatment to induce POI cell models and then received quercetin treatment, and experimentally validated the network pharmacology prediction results by TUNEL staining and Western blotting assay. Results: The TCMSP database provided 32 active compounds and 552 target genes associated with Huangqi, while totally 730 disease target genes associated with POI were screened out from the disease database. Of these, 62 genes were found to be shared between the two datasets. The top 6 compounds based on degree values were quercetin, isorhamnetin, kaempferol, mairin, formononetin and astragaloside IV. The 10 core genes identified were ALB, INS, AKT1, ACTB, TP53, TNF, ESR1, CASP3, STAT3 and PTEN. These potential targets were mainly involved in regulating the JAK2/STAT3 and PI3K/Akt signaling pathway. Molecular docking results revealed strong binding interactions between the compounds and the key proteins STAT3 and Akt1 in the JAK-STAT and PI3K-Akt signalling pathways. The results of in vitro experiments revealed that quercetin could activate the JAK2/STAT3 pathway and inhibit cell apoptosis. Conclusions: Network pharmacology and molecular docking analysis showed that Astragalus could regulate the response of ovarian cells to estradiol, inhibit apoptosis and regulate the JAK-STAT and PI3K-Akt signalling pathways in the treatment of early onset ovarian dysfunction. [ABSTRACT FROM AUTHOR]

Ion channels, in particular transient–receptor potential (TRP) channels, are essential genes that play important roles in many physiological processes. Emerging evidence has demonstrated that TRP genes are involved in a number of diseases, including various cancer types. However, we still lack knowledge about the expression alterations landscape of TRP genes across cancer types. In this review, we comprehensively reviewed and summarised the transcriptomes from more than 10 000 samples in 33 cancer types. We found that TRP genes were widespreadly transcriptomic dysregulated in cancer, which was associated with clinical survival of cancer patients. Perturbations of TRP genes were associated with a number of cancer pathways across cancer types. Moreover, we reviewed the functions of TRP family gene alterations in a number of diseases reported in recent studies. Taken together, our study comprehensively reviewed TRP genes with extensive transcriptomic alterations and their functions will directly contribute to cancer therapy and precision medicine. [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.

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]