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OBJECTIVES: We aimed to construct an artificial intelligence-enabled electrocardiogram (ECG) algorithm that can accurately predict the presence of left atrial low-voltage areas (LVAs) in patients with persistent atrial fibrillation. METHODS: The study included 587 patients with persistent atrial fibrillation who underwent catheter ablation procedures between March 2012 and December 2023 and 942 scanned images of 12-lead ECGs obtained before the ablation procedures were performed. Artificial intelligence-based algorithms were used to construct models for predicting the presence of LVAs. The DR-FLASH and APPLE clinical scores for LVA prediction were calculated. We used a receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis to evaluate model performance. RESULTS: The data obtained from the participants were split into training (n = 469), validation (n = 58), and test sets (n = 60). LVAs were detected in 53.7% of all participants. Using ECG alone, the deep learning algorithm achieved an area under the ROC curve (AUROC) of 0.752, outperforming both the DR-FLASH score (AUROC = 0.610) and the APPLE score (AUROC = 0.510). The random forest classification model, which integrated a probabilistic deep learning model and clinical features, showed a maximum AUROC of 0.759. Moreover, the ECG-based deep learning algorithm for predicting extensive LVAs achieved an AUROC of 0.775, with a sensitivity of 0.816 and a specificity of 0.896. The random forest classification model for predicting extensive LVAs achieved an AUROC of 0.897, with a sensitivity of 0.862, and a specificity of 0.935. CONCLUSION: The deep learning model based exclusively on ECG data and the machine learning model that combined a probabilistic deep learning model and clinical features both predicted the presence of LVAs with a higher degree of accuracy than the DR-FLASH and the APPLE risk scores.
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Open-pit mine pavement dust dries and breaks easily. As such, a composite pavement dust suppressant with good wettability, moisturizing, coagulation, and antifreezing properties in winter was investigated. Monomer screening and orthogonal experiments were conducted, using evaporation rate, permeability rate, viscosity, and freezing point as evaluation indexes. Consequently, a dust suppressant solution is a mixture of glycerol (GLY), sodium dodecylbenzene sulfonate (SDBS), polyacrylamide (PAM), compound propylene glycol (PG), and potassium acetate (PA). The characteristics of the dust suppressant and its interaction mechanism with road dust were measured and analyzed. The results showed that the optimal ratio of the antifreeze-type composite dust suppressant is 3%GLY, 0.30%SDBS, 0.07% PAM, and 50%PG + 10%PA; the contact angle is 27.62°, which can effectively wet coal dust. Moreover, it easily forms hydrogen bonds with water molecules to release free -OH, which increases the oxygen-containing functional groups in the dust. The maximum viscosity is 25.4 mPa·s, and the hydrophobic groups adsorbed on the surface of the dust can condense and agglomerate the dust to form large particles, and effectively inhibit the occurrence of dust. It freezes at - 34.2 â, resists a temperature of - 30 â without freezing, and improves dust suppression efficiency and antifreezing effect in cold areas.
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Ulcerative colitis (UC) is characterized by an abnormal immune response, and the pathogenesis lacks clear understanding. The cGAS-STING pathway is an innate immune signaling pathway that plays a significant role in various pathophysiological processes. However, the role of the cGAS-STING pathway in UC remains largely unclear. In this study, we obtained transcriptome sequencing data from multiple publicly available databases. cGAS-STING related genes were obtained through literature search, and differentially expressed genes (DEGs) were analyzed using R package limma. Hub genes were identified through protein-protein interaction (PPI) network analysis and module construction. The ConsensuClusterPlus package was utilized to identify molecular subtypes based on hub genes. The therapeutic response, immune microenvironment, and biological pathways of subtypes were further investigated. A total of 18 DEGs were found in UC patients. We further identified IFI16, MB21D1 (CGAS), TMEM173 (STING) and TBK1 as the hub genes. These genes are highly expressed in UC. IFI16 exhibited the highest diagnostic value and predictive value for response to anti-TNF therapy. The expression level of IFI16 was higher in non-responders to anti-TNF therapy. Furthermore, a cluster analysis based on genes related to the cGAS-STING pathway revealed that patients with higher gene expression exhibited elevated immune burden and inflammation levels. This study is a pioneering analysis of cGAS-STING pathway-related genes in UC. These findings provide new insights for the diagnosis of UC and the prediction of therapeutic response.
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Colitis Ulcerosa , Proteínas de la Membrana , Nucleotidiltransferasas , Transducción de Señal , Humanos , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Colitis Ulcerosa/genética , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inmunología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Transducción de Señal/genética , Mapas de Interacción de Proteínas/genética , Perfilación de la Expresión Génica , TranscriptomaRESUMEN
Dysregulation and enhanced expression of MYC transcription factors (TFs) including MYC and MYCN contribute to the majority of human cancers. For example, MYCN is amplified up to several hundredfold in high-risk neuroblastoma. The resulting overexpression of N-myc aberrantly activates genes that are not activated at low N-myc levels and drives cell proliferation. Whether increasing N-myc levels simply mediates binding to lower-affinity binding sites in the genome or fundamentally changes the activation process remains unclear. One such activation mechanism that could become important above threshold levels of N-myc is the formation of aberrant transcriptional condensates through phase separation. Phase separation has recently been linked to transcriptional regulation, but the extent to which it contributes to gene activation remains an open question. Here we characterized the phase behavior of N-myc and showed that it can form dynamic condensates that have transcriptional hallmarks. We tested the role of phase separation in N-myc-regulated transcription by using a chemogenetic tool that allowed us to compare non-phase-separated and phase-separated conditions at equivalent N-myc levels, both of which showed a strong impact on gene expression compared to no N-myc expression. Interestingly, we discovered that only a small percentage (<3%) of N-myc-regulated genes is further modulated by phase separation but that these events include the activation of key oncogenes and the repression of tumor suppressors. Indeed, phase separation increases cell proliferation, corroborating the biological effects of the transcriptional changes. However, our results also show that >97% of N-myc-regulated genes are not affected by N-myc phase separation, demonstrating that soluble complexes of TFs with the transcriptional machinery are sufficient to activate transcription.
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We reported a novel variant in Kallmann syndrome. It not only determines the clinical importance of whole exome sequencing for identification of genetic pathogenic variants, but also enriches the ANOS1 genetic spectrum of CHH patients in Chinese population.
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Background: Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer. Methods: Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs). Results: Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18-1.27) in men, and 1.26 (1.22-1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10-2.51) for men and 1.94 (1.78-2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = -1.01 in men, p<0.001; Beta = -0.98 in women, p<0.001). Conclusions: Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle. Funding: This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).
Age is a major risk factor for cancer. Other factors, such as lifestyle or environmental exposures, may increase or mitigate cancer risks. Biological age, which considers accelerated aging processes, may, however, better predict cancer risk than chronological age. Some scientists propose using biological aging measures as an alternative for assessing cancer and other age-related disease risks, as these markers may provide a more accurate assessment of the various factors contributing to cancer risk. PhenoAge, a measure of biological aging processes in the body, could provide an alternative way to assessing aging-related cancer risks. This tool utilizes an individual's chronological age and nine biomarkers of aging processes. It has the potential to identify individuals whose aging process is accelerated compared to their peers, potentially indicating an increased cancer risk. This information may empower them to make lifestyle changes that could significantly reduce their risk. To assess the suitability of PhenoAge, Bian, Ma et al. used nine clinical chemistry biomarkers and chronological age to calculate PhenoAge in 374,463 participants from the UK Biobank. Their findings revealed that people with older PhenoAges regardless of their genetic risk profiles have an increased risk of cancer. Individuals with higher PhenoAge scores, indicating accelerated biological aging, had a roughly 25 percent higher risk of developing cancer. Individuals with both a high genetic risk and higher PhenoAge score had roughly double the risk of cancer. People with lower PhenoAges were more likely to have healthier lifestyles. These results suggest that adopting healthier lifestyles may slow the aging process and reduce cancer risk. While the analyses conducted by Bian, Ma et al. provide promising insights, they also underscore the need for further research. PhenoAge may offer a way to assess biological aging and identify individuals at higher risk of cancer. Those with higher PhenoAge scores may benefit from earlier cancer screening, and adopting a healthier lifestyle could potentially slow down the aging process and reduce their cancer risk. However, more studies in more diverse cohorts of people are needed to confirm that PhenoAge is a reliable marker for cancer risk and to test interventions to slow aging and reduce cancer risks in individuals with accelerated aging.
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Envejecimiento , Neoplasias , Fenotipo , Humanos , Neoplasias/genética , Neoplasias/epidemiología , Masculino , Femenino , Envejecimiento/genética , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Incidencia , Factores de Riesgo , Predisposición Genética a la Enfermedad , Reino Unido/epidemiología , Adulto , Modelos de Riesgos ProporcionalesRESUMEN
Dynamic control of ultralong organic room-temperature phosphorescence (UORTP) is a charming target. Herein, we report a stimuli-responsive phosphorescence unit 7H-indolo[2,3-c]quinoline (NBCz) and its derivatives (PCBNBCz, FSO2NBCz, and N2BCzSO2NBCz) that show photo- and oxygen- synergistically induced afterglow activation and afterglow color change in the PMMA film. PCBNBCz and FSO2NBCz feature a donor-acceptor (D-A) structure, and N2BCzSO2NBCz features acceptor-bridged two different phosphorescence units (NBCz and N2BCz). The photoactivated UORTP of PCBNBCz and FSO2NBCz arises from the photoinduced consumption of oxygen in the PMMA film. It is clear that the phosphorescence unit NBCz contributes to subsequent photoinduced UORTP color change because the NBCz-doped PMMA film shows the same UORTP color change process. ESR and HRMS measurements confirmed that oxidation of NBCz occurs at the nitrogen atom of the quinoline ring via photogenerated superoxide radicals, which results in the UORTP color change. TDDFT calculations proved that after oxidation of NBCz, the T1 energy level declines significantly. Furthermore, photocontrolled selective expression of phosphorescence units is achieved in the case of N2BCzSO2NBCz. After further UV irradiation, oxidation of NBCz happened, and the oxidized form N2BCzSO2NBCz-O emitted the intrinsic orange UORTP of NBCz-O selectively and screened the intrinsic yellowish-green UORTP of N2BCz. Finally, multilevel photolithography can be demonstrated based on the photoactivated UORTP and the photoinduced UORTP color change. This work may give a deep insight into organic phosphorescence and pave a simple way for the development of stimulus-responsive smart UORTP materials.
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BACKGROUND: Insulin resistance has been reported to increase the risk of breast, prostate and colorectal cancer. However, the role of insulin resistance and its interaction with genetic risk in the development of lung cancer remains controversial. Therefore, we aimed to explore the association between a novel metabolic score for insulin resistance (METS-IR) and lung cancer risk. METHODS: A total of 395 304 participants without previous cancer at baseline were included. The Cox proportional hazards regression model was performed to investigate the association between METS-IR and lung cancer risk. In addition, a Mendelian randomization analysis was also performed to explore the causal relationship. The joint effects and additive interactions between METS-IR and polygenetic risk score (PRS) of lung cancer were also investigated. RESULTS: During a median follow-up of 11.03 years (Inter-quartile range (IQR): 10.30-11.73), a total of 3161 incident lung cancer cases were diagnosed in 395 304 participants. There was a significant association between METS-IR and lung cancer risk, with an HR of 1.28 (95% CI: 1.17-1.41). Based on the Mendelian randomization analysis, however, no causal associations were observed. We observed a joint effect but no interaction between METS-IR and genetic risk. The lung cancer incidence was estimated to be 100.42 (95% CI: 91.45-109.38) per 100 000 person-year for participants with a high METS-IR and PRS, while only 42.76 (95% CI: 36.94-48.59) with low METS-IR and PRS. CONCLUSIONS: High METS-IR was significantly associated with an increased risk of lung cancer. Keeping a low level of METS-IR might help reduce the long-term incident risk of lung cancer.
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Resistencia a la Insulina , Neoplasias Pulmonares , Análisis de la Aleatorización Mendeliana , Humanos , Neoplasias Pulmonares/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Síndrome Metabólico/epidemiología , Adulto , Modelos de Riesgos Proporcionales , Anciano , IncidenciaRESUMEN
As molecular design and the structure-property relationships of photochemical molecules established in the literature serve as a convenient reference for mechanophore exploration, many typical mechanophores suffer undesired responses to UV light or even sunlight in bulk polymers. We developed a strategy of a poly(methyl acrylate)/polyurethane (PMA/PU) interpenetrating polymer network (IPN) to suppress the photochromic property of the mechanophore and promote its mechanochromic property. A widely used rhodamine mechanophore (Rh-2OH) was first incorporated into polyurethane (P1). Then P1 was swollen in methyl acrylate and photopolymerized to prepare a PMA2.8/PU IPN (P2). Different from photo/force-responsive P1, P2 selectively responded to force because the low free volume in IPN greatly hinders photoisomerization of the rhodamine spirolactam, suggesting that a simple IPN strategy successfully resolves the giant problem of nonselective response to photo/force for photochromic mechanophores. Moreover, PMA/PU IPN enhanced the mechanical property, resulting in a higher mechanochemical activation ratio than PU, and the prestretching effect of PMA/PU IPN promoted the force sensitivity of rhodamine mechanophores significantly. We believe that the strategy can be applied to other mechanophores, promoting their application in more complicated environments.
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Phase separation (PS) drives the formation of biomolecular condensates that are emerging biological structures involved in diverse cellular processes. Recent studies have unveiled PS-induced formation of several transcriptional factor (TF) condensates that are transcriptionally active, but how strongly PS promotes gene activation remains unclear. Here, we show that the oncogenic TF fusion Yes-associated protein 1-Mastermind like transcriptional coactivator 2 (YAP-MAML2) undergoes PS and forms liquid-like condensates that bear the hallmarks of transcriptional activity. Furthermore, we examined the contribution of PS to YAP-MAML2-mediated gene expression by developing a chemogenetic tool that dissolves TF condensates, allowing us to compare phase-separated and non-phase-separated conditions at identical YAP-MAML2 protein levels. We found that a small fraction of YAP-MAML2-regulated genes is further affected by PS, which include the canonical YAP target genes CTGF and CYR61, and other oncogenes. On the other hand, majority of YAP-MAML2-regulated genes are not affected by PS, highlighting that transcription can be activated effectively by diffuse complexes of TFs with the transcriptional machinery. Our work opens new directions in understanding the role of PS in selective modulation of gene expression, suggesting differential roles of PS in biological processes.
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Separación de Fases , Transcriptoma , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , OncogenesRESUMEN
The proportion of lung cancer in never smokers is rising, especially among Asian women, but there is no effective early detection tool. Here, we developed a polygenic risk score (PRS), which may help to identify the population with higher risk of lung cancer in never-smoking women. We first performed a large GWAS meta-analysis (8595 cases and 8275 controls) to systematically identify the susceptibility loci for lung cancer in never-smoking Asian women and then generated a PRS using GWAS datasets. Furthermore, we evaluated the utility and effectiveness of PRS in an independent Chinese prospective cohort comprising 55 266 individuals. The GWAS meta-analysis identified eight known loci and a novel locus (5q11.2) at the genome-wide statistical significance level of P < 5 × 10-8 . Based on the summary statistics of GWAS, we derived a polygenic risk score including 21 variants (PRS-21) for lung cancer in never-smoking women. Furthermore, PRS-21 had a hazard ratio (HR) per SD of 1.29 (95% CI = 1.18-1.41) in the prospective cohort. Compared with participants who had a low genetic risk, those with an intermediate (HR = 1.32, 95% CI: 1.00-1.72) and high (HR = 2.09, 95% CI: 1.56-2.80) genetic risk had a significantly higher risk of incident lung cancer. The addition of PRS-21 to the conventional risk model yielded a modest significant improvement in AUC (0.697 to 0.711) and net reclassification improvement (24.2%). The GWAS-derived PRS-21 significantly improves the risk stratification and prediction accuracy for incident lung cancer in never-smoking Asian women, demonstrating the potential for identification of high-risk individuals and early screening.
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Neoplasias Pulmonares , Humanos , Femenino , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Puntuación de Riesgo Genético , Predisposición Genética a la Enfermedad , Estudios de Cohortes , Estudios Prospectivos , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Fumar/genética , Fumar/epidemiología , ChinaRESUMEN
We successfully tune ultralong organic room-temperature phosphorescence (UORTP) by a simple strategy of precisely modifying nitrogen atoms on Phosphorescence Units, and colorful ultralong phosphorescence can be achieved. We for the first time investigate the structure-function relationship between phosphorescence properties and molecular structures of Phosphorescence Units. With BCz and BCz-1 as comparison, eight new Phosphorescence Units were synthesized by introducing one or two nitrogen atoms to the naphthalene moiety. For all the 10 Phosphorescence Units, their room-temperature ultralong phosphorescence in the PMMA film should be assigned to monomer phosphorescence from intrinsic T1 decay. For Phosphorescence Units series I (BCz, NBCz-1, NBCz-2, NBCz-3, NBCz-4, NBCz-5, and NBCz-6), introducing one nitrogen atom to the naphthalene moiety can significantly affect the phosphorescence properties of Phosphorescence Units, and the effect is quite complicated. For modification on the inner ring, the T1 energy level of NBCz-1 decreases, and the red shift of UORTP occurs while the T1 energy level of NBCz-2 increases and the blue shift of UORTP happens. For modification on the outer ring, no phosphorescence color change is observed for NBCz-3 and NBCz-4, but their phosphorescence lifetimes vary notably due to different intersystem crossing efficiencies; as the modification site approaches the central five-member ring, the T1 energy levels of NBCz-5 and NBCz-6 decrease, and their UORTP red shifts dramatically. For Phosphorescence Units series II (BCz, 2NBCz, BCz-1, and 2NBCz-1), introducing two nitrogen atoms to the outer six-member ring reduces energy level of T1 excitons and leads to incredible red shift of UORTP for BCz and 2NBCz while surprisingly energy levels of T1 excitons rise and UORTP blue shifts for BCz-1 and 2NBCz-1. Under the condition of proper modification sites, it is true that the more the additional nitrogen atoms, the more red-shifted the ultralong phosphorescence. This study may expand our knowledge of organic phosphorescence and lay the foundation for its future applications.
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The supercritical antisolvent-fluidized bed coating process (SAS-FB) shows great potential as a technique to manufacture dry powder inhaler (DPI) that incorporate nanodrugs onto micronized matrix particles, capitalizing on the merits of both nanoparticle and pulmonary delivery. In this study, naringin (NAR), a pharmacologically active flavonoid with low solubility and in vivo degradation issues, was utilized as a model active pharmaceutical ingredient to construct nanomedicine-based DPI through SAS-FB. It is showed that processed NAR exhibited a near-spherical shape and an amorphous structure with an average size of around 130 nm. Notably, SAS-FB products prepared with different fluidized matrices resulted in varying deposition patterns, particularly when mixed with a coarse lactose to enhance the fine particle fraction (FPF) of the formulations. The FPF was positively associated with specific surface area of the SAS-FB products, while the specific surface area was directly related to surface roughness and particle size. In vitro dissolution studies using simulated lung fluid revealed that the NAR nanoparticles coated on the products were released immediately upon contact with solution, with a cumulative dissolution exceeding 90% within the first minute. Importantly, compared to oral raw NAR, the optimized DPI formulation demonstrated superior in vivo plasmatic and pulmonary AUC0â∞ by 51.33-fold and 104.07-fold respectively in a Sprague-Dawley rat model. Overall, SAS- FB technology provides a practical approach to produce nanomedicine DPI product that combine the benefits of nanoparticles with the aerodynamics properties of inhaled microparticles.
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Inhaladores de Polvo Seco , Nanomedicina , Ratas , Animales , Inhaladores de Polvo Seco/métodos , Ratas Sprague-Dawley , Administración por Inhalación , Pulmón , Tamaño de la Partícula , PolvosRESUMEN
Fruit crops, consist of climacteric and non-climacteric fruits, are the major sources of nutrients and fiber for human diet. Since 2013, CRISPR/Cas (Clustered Regularly Interspersed Short Palindromic Repeats and CRISPR-Associated Protein) genome editing system has been widely employed in different plants, leading to unprecedented progress in the genetic improvement of many agronomically important fruit crops. Here, we summarize latest advancements in CRISPR/Cas genome editing of fruit crops, including efforts to decipher the mechanisms behind plant development and plant immunity, We also highlight the potential challenges and improvements in the application of genome editing tools to fruit crops, including optimizing the expression of CRISPR/Cas cassette, improving the delivery efficiency of CRISPR/Cas reagents, increasing the specificity of genome editing, and optimizing the transformation and regeneration system. In addition, we propose the perspectives on the application of genome editing in crop breeding especially in fruit crops and highlight the potential challenges. It is worth noting that efforts to manipulate fruit crops with genome editing systems are urgently needed for fruit crops breeding and demonstration.
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BACKGROUND: The role of genetic background underlying the disparity of relative risk of smoking and lung cancer between European populations and East Asians remains unclear. METHODS: To assess the role of ethnic differences in genetic factors associated with smoking-related risk of lung cancer, we first constructed ethnic-specific polygenic risk scores (PRSs) to quantify individual genetic risk of lung cancer in Chinese and European populations. Then, we compared genetic risk and smoking as well as their interactions on lung cancer between two cohorts, including the China Kadoorie Biobank (CKB) and the UK Biobank (UKB). We also evaluated the absolute risk reduction over a 5-year period. RESULTS: Differences in compositions and association effects were observed between the Chinese-specific PRSs and European-specific PRSs, especially for smoking-related loci. The PRSs were consistently associated with lung cancer risk, but stronger associations were observed in smokers of the UKB [hazard ratio (HR) 1.26 vs 1.15, P = 0.028]. A significant interaction between genetic risk and smoking on lung cancer was observed in the UKB (RERI, 11.39 (95% CI, 7.01-17.94)], but not in the CKB. Obvious higher absolute risk was observed in nonsmokers of the CKB, and a greater absolute risk reduction was found in the UKB (10.95 vs 7.12 per 1000 person-years, P <0.001) by comparing heavy smokers with nonsmokers, especially for those at high genetic risk. CONCLUSIONS: Ethnic differences in genetic factors and the high incidence of lung cancer in nonsmokers of East Asian ethnicity were involved in the disparity of smoking-related risk of lung cancer.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Estudios Prospectivos , Fumar/efectos adversos , Fumar/genética , Factores de Riesgo , Fumar Tabaco , Puntuación de Riesgo GenéticoRESUMEN
This dataset provides a collection of 24 h electrocardiograph (ECG) signals, ECG analysis results based on circadian rhythm and R-peak detection, results of sleep quality assessment and clinical indicators of metabolic function acquired from 60 male type 2 diabetes mellitus (T2DM) inpatients. Upon admission, a fasting blood draw and urinary sample were obtained the next morning for routine glucose, lipid and renal panels. Subjects were also involved in investigation for diabetic complications. On the second day of hospitalization, subjects were monitored in hospital for 24-h ECG starting at 10 pm. Subjective sleep quality was assessed by Pittsburgh Sleep Quality Index and a brief sleep log was used to record sleep duration for the studied night. Objective sleep quality and sleep staging were assessed by cardiopulmonary coupling analysis. This dataset could be utilized to conduct conjoint research on the relationships among sleep, metabolic function, and function of cardiovascular system and autonomic nervous system derived from ECG analysis in T2DM, and further investigate the information in ECG signals based on circadian rhythm and physiological status, providing new insights into long term physiological signal processing.
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Belonging to Rosaceae, red raspberry (Rubus idaeus) and wild strawberry (Fragaria vesca) are closely related species with distinct fruit types. While the numerous ovaries become the juicy drupelet fruits in raspberry, their strawberry counterparts become dry and tasteless achenes. In contrast, while the strawberry receptacle, the stem tip, enlarges to become a red fruit, the raspberry receptacle shrinks and dries. The distinct fruit-forming ability of homologous organs in these 2 species allows us to investigate fruit type determination. We assembled and annotated the genome of red raspberry (R. idaeus) and characterized its fruit development morphologically and physiologically. Subsequently, transcriptomes of dissected and staged raspberry fruit tissues were compared to those of strawberry from a prior study. Class B MADS box gene expression was negatively associated with fruit-forming ability, which suggested a conserved inhibitory role of class B heterodimers, PISTILLATA/TM6 or PISTILLATA/APETALA3, for fruit formation. Additionally, the inability of strawberry ovaries to develop into fruit flesh was associated with highly expressed lignification genes and extensive lignification of the ovary pericarp. Finally, coexpressed gene clusters preferentially expressed in the dry strawberry achenes were enriched in "cell wall biosynthesis" and "ABA signaling," while coexpressed clusters preferentially expressed in the fleshy raspberry drupelets were enriched in "protein translation." Our work provides extensive genomic resources as well as several potential mechanisms underlying fruit type specification. These findings provide the framework for understanding the evolution of different fruit types, a defining feature of angiosperms.
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Fragaria , Rubus , Rubus/genética , Frutas/metabolismo , Transcriptoma/genética , GenómicaRESUMEN
Background: Emerging evidence suggests a potential link between psychological distress (anxiety and depression) and lung cancer risk, however, it is unclear whether other factors such as tobacco smoking and genetic susceptibility modify the association. Methods: We included 405,892 UK Biobank participants free of cancer at baseline. Psychological distress was measured using the Patient Health Questionnaire-4 (PHQ-4). A polygenic risk score (PRS) was calculated using 18 lung cancer-associated genetic loci. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During a median follow-up of 7.13 years, 1754 lung cancer cases were documented. The higher score of psychological distress was associated with an increased risk of lung cancer (HRper 1-SD= 1.07, 95% CI: 1.02-1.11) after adjustment for smoking and other confounders. Mediation analysis revealed that 16.8% (95% CI: 13.0%-20.6%) of the distress-lung cancer association was mediated by smoking. Compared with never smokers with no distress, participants with heavy smoking and high distress had the highest risk of lung cancer (HR=18.57, 95% CI: 14.51-23.76). Both multiplicative and additive interactions were observed between smoking and psychological distress in lung cancer. Furthermore, the greatest relative increase in risk was observed among those with high genetic risk and high distress (HR=1.87, 95%CI: 1.50-2.33), and there was a significant additive interaction between the PRS and psychological distress. Conclusion: Our results indicate that psychological distress was associated with an elevated risk of incident lung cancer, and such relation was modified by tobacco smoking and genetic susceptibility.
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BACKGROUND: Most lung cancer risk prediction models were developed in European and North-American cohorts of smokers aged ≥ 55 years, while less is known about risk profiles in Asia, especially for never smokers or individuals aged < 50 years. Hence, we aimed to develop and validate a lung cancer risk estimate tool for ever and never smokers across a wide age range. METHODS: Based on the China Kadoorie Biobank cohort, we first systematically selected the predictors and explored the nonlinear association of predictors with lung cancer risk using restricted cubic splines. Then, we separately developed risk prediction models to construct a lung cancer risk score (LCRS) in 159,715 ever smokers and 336,526 never smokers. The LCRS was further validated in an independent cohort over a median follow-up of 13.6 years, consisting of 14,153 never smokers and 5,890 ever smokers. RESULTS: A total of 13 and 9 routinely available predictors were identified for ever and never smokers, respectively. Of these predictors, cigarettes per day and quit years showed nonlinear associations with lung cancer risk (Pnon-linear < 0.001). The curve of lung cancer incidence increased rapidly above 20 cigarettes per day and then was relatively flat until approximately 30 cigarettes per day. We also observed that lung cancer risk declined sharply within the first 5 years of quitting, and then continued to decrease but at a slower rate in the subsequent years. The 6-year area under the receiver operating curve for the ever and never smokers' models were respectively 0.778 and 0.733 in the derivation cohort, and 0.774 and 0.759 in the validation cohort. In the validation cohort, the 10-year cumulative incidence of lung cancer was 0.39% and 2.57% for ever smokers with low (< 166.2) and intermediate-high LCRS (≥ 166.2), respectively. Never smokers with a high LCRS (≥ 21.2) had a higher 10-year cumulative incidence rate than those with a low LCRS (< 21.2; 1.05% vs. 0.22%). An online risk evaluation tool (LCKEY; http://ccra.njmu.edu.cn/lckey/web) was developed to facilitate the use of LCRS. CONCLUSIONS: The LCRS can be an effective risk assessment tool designed for ever and never smokers aged 30 to 80 years.