Neutrophil extracellular traps trigger alveolar epithelial cell necroptosis through the cGAS-STING pathway during acute lung injury in mice.

Extensive loss of alveolar epithelial cells (AECs) undergoing necroptosis is a crucial mechanism of acute lung injury (ALI), but its triggering mechanism needs to be thoroughly investigated. Neutrophil extracellular traps (NETs) play a significant role in ALI. However, the effect of NETs on AECs' death has not been clarified. Our study found that intratracheal instillation of NETs disrupted lung tissue structure, suggesting that NETs could induce ALI in mice. Moreover, we observed that NETs could trigger necroptosis of AECs in vivo and in vitro. The phosphorylation levels of RIPK3 and MLKL were increased in MLE12 cells after NETs treatment (P < 0.05). Mechanistically, NETs taken up by AECs through endocytosis activated the cGAS-STING pathway and triggered AECs necroptosis. The expression of cGAS, STING, TBK1 and IRF3 were increased in MLE12 cells treated with NETs (P < 0.05). Furthermore, the cGAS inhibitor RU.521 inhibited NETs-triggered AECs necroptosis and alleviated the pulmonary damage induced by NETs in mice. In conclusion, our study demonstrates that NETs taken up by AECs via endocytosis can activate the cGAS-STING pathway and trigger AECs necroptosis to promote ALI in mice. Our findings indicate that targeting the NETs/cGAS-STING/necroptosis pathway in AECs is an effective strategy for treating ALI.

Analysis of resting status reveals distinct elevational variation in metabolisms of lizards.

Animals spend a considerable proportion of their life span at rest. However, resting status has often been overlooked when investigating how species respond to environmental conditions. This may induce a large bias in understanding the local adaptation of species across environmental gradients and their vulnerability to potential environmental change. Here, we conducted an empirical study on montane agamid lizards, combined with mechanistic modeling, to compare elevational variations in body temperature and metabolisms (cumulative digestion and maintenance cost) between resting and active status. Our study on three populations of an agamid lizard along an elevational gradient revealed a trend of decreasing body temperature toward higher elevations, the main contributor of which was resting status of the lizards. Using population-specific reaction norms, we predicted greater elevational variation in hourly and cumulative digestion for resting lizards than for active lizards. Climate-change impacts, estimated as the change in cumulative digestion, also show greater elevational variation when resting status is factored into the analysis. Further, our global analysis of 98 agamid species revealed that in about half of their combined distributional range, the contribution of resting status in determining the elevational variation in cumulative digestion and maintenance cost of lizards was greater than the contribution made by a lizard's active status. Our study highlights the importance of considering resting status when investigating how species respond to environmental conditions, especially for those distributed over tropical and subtropical mountain areas.

MEOX1 triggers myofibroblast apoptosis resistance, contributing to pulmonary fibrosis in mice.

The apoptosis resistance of myofibroblasts is a hallmark in the irreversible progression of pulmonary fibrosis (PF). While the underlying molecular mechanism remains elusive. In this study, we unveiled a previously unrecognized mechanism underlying myofibroblast apoptosis resistance during PF. Our investigation revealed heightened expression of mesenchyme homeobox 1 (MEOX1) in the lungs of idiopathic pulmonary fibrosis (IPF) patients and bleomycin-induced PF mice. Silencing MEOX1 significantly attenuated PF progression in mice. In vitro, we found a notable increase in MEOX1 expression in transforming growth factor-ß1 (TGF-ß1)-induced myofibroblasts. Silencing MEOX1 enhanced apoptosis of myofibroblasts. Mechanistically, we identified G-protein signaling pathway regulatory factor 4 (RGS4) as a critical downstream target of MEOX1, as predicted by bioinformatics analysis. MEOX1 enhanced apoptosis resistance by upregulating RGS4 expression in myofibroblasts. In conclusion, our study highlights MEOX1 as a promising therapeutic target for protecting against PF by modulating myofibroblast apoptosis resistance.

Krüppel-like transcription factor 14 alleviates alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress in pulmonaryfibrosis.

Pulmonary fibrosis (PF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia, occurring primarily in older adults with poor prognosis. Alveolar epithelial cell (AEC) senescence is the critical pathological mechanism of PF. However, the molecular mechanisms regulating AEC senescence in PF are incompletely understood. Herein, we provided evidence to support the function of Krüppel-like factor 14 (KLF14), a novel Krüppel-like transcription factor, in the regulation of AEC senescence during PF. We confirmed that the expression of KLF14 was up-regulated in PF patients and mice treated with bleomycin (BLM). KLF14 knockdown resulted in more pronounced structural disruption of the lung tissue and swelling of the alveolar septum, which led to significantly increased mortality in BLM-induced PF mice. Mechanistically, RNA-seq analysis indicated that KLF14 decreased the senescence of AECs by inhibiting endoplasmic reticulum (ER) stress. Furthermore, the pharmacological activation of KLF14 conferred protection against PF in mice. In conclusion, our findings reveal a protective role for KLF14 in preventing AECs from senescence and shed light on the development of KLF14-targeted therapeutics for PF.

Radiomics-based Support Vector Machine Distinguishes Molecular Events Driving Progression of Lung Adenocarcinoma.

INTRODUCTION: An increasing number of early-stage lung adenocarcinoma (LUAD) are detected as lung nodules. The radiological features related to LUAD progression remain further investigation. Exploration is required to bridge the gap between radiomics features and molecular characteristics of lung nodules. METHODS: Consensus clustering was applied to the radiomics features of 1,212 patients to establish stable clustering. Clusters were illustrated using clinicopathological and next-generation sequencing (NGS). A classifier was constructed to further investigate the molecular characteristic in patients with paired CT and RNA-seq data. RESULTS: Patients were clustered into 4 clusters. Cluster 1 was associated with a low consolidation-to-tumor ratio (CTR), pre-invasion, grade I disease and good prognosis. Clusters 2 and 3 showed increasing malignancy with higher CTR, higher pathological grade and poor prognosis. Cluster 2 possessed more spread through air spaces (STAS) and cluster 3 showed higher proportion of pleural invasion. Cluster 4 had similar clinicopathological features with cluster 1 except higher proportion of grade II disease. RNA-seq indicated that cluster 1 represented nodules with indolent growth and good differentiation, whereas cluster 4 showed progression in cell development but still had low proliferative activity. Nodules with high proliferation were classified into clusters 2 and 3. Additionally, the radiomics classifier distinguished cluster 2 as nodules harboring an activated immune environment, while cluster 3 represented nodules with a suppressive immune environment. Furthermore, gene signatures associated with the prognosis of early-stage LUAD were validated in external datasets. CONCLUSION: Radiomics features can manifest molecular events driving progression of lung adenocarcinoma. Our study provides a molecular insight into radiomics features and assists in the diagnosis and treatment of early stage LUAD.

A Multifunctional Nanoparticle Dual Loading with Chlorin e6 and STING Agonist for Combinatorial Therapy of Melanoma.

Photodynamic therapy (PDT) is a noninvasive therapeutic approach that is effective in killing primary tumors with minimal surgical trauma, but its usage in metastatic lesions of melanoma is restricted by spatial limitations. Recently, stimulator of interferon genes (STING) agoinst-mediated innate immunity can activate the STING pathway and further promote dendritic cell (DC) maturation, tumor-specific cytotoxic T lymphocyte, and natural killer cell infiltration and has emerged as a promising approach for cancer therapy. Herein, the authors intriduce facile nanoparticles named HTCS, which can co-deliver STING agonist (2'3'-cGAMP) and a mitochondrial targeting modified photosensitizer (TPP-PEI-Ce6). While HTCS were intravenously injected to mice, they were endocytosed into tumor cells through hyaluronic acid-mediated active targeting. Thereafter, TPP-PEI-Ce6 was delivered to mitochondria to generate a large variety of reactive oxygen species and killed tumor cells effectively. Then the tumor cell debris further gave rise to immunogenic cell death, which played a role in immunosuppression. Furthermore, 2'3'-cGAMP contained in cell debris activated the STING pathway to promote the release of inflammatory cytokines and the maturation of DCs. As a consequence, the HTCS could achieve photodynamic multiple immunotherapy for melanoma. This work demonstrates multifunctional nanoparticles that efficiently inhibit tumors by PDT and reversing their immunosuppression to realize a versatile therapeutic strategy.

International Alliance of Urolithiasis (IAU) guidelines on the management of pediatric urolithiasis.

The aim of this study was to construct the sixth in a series of guidelines on the treatment of urolithiasis by the International Alliance of Urolithiasis (IAU) that by providing a clinical framework for the management of pediatric patients with urolithiasis based on the best available published literature. All recommendations were summarized following a systematic review and assessment of literature in the PubMed database from January 1952 to December 2023. Each generated recommendation was graded using a modified GRADE methodology. Recommendations are agreed upon by Panel Members following review and discussion of the evidence. Guideline recommendations were developed that addressed the following topics: etiology, risk factors, clinical presentation and symptoms, diagnosis, conservative management, surgical interventions, prevention, and follow-up. Similarities in the treatment of primary stone episodes between children and adults, incorporating conservative management and advancements in technology for less invasive stone removal, are evident. Additionally, preventive strategies aiming to reduce recurrence rates, such as ensuring sufficient fluid intake, establishing well-planned dietary adjustments, and selective use pharmacologic therapies will also result in highly successful outcomes in pediatric stone patients. Depending on the severity of metabolic disorders and also anatomical abnormalities, a careful and close follow-up program should inevitably be planned in each pediatric patient to limit the risk of future recurrence rates.

Metabolically activated energetic materials mediate cellular anabolism for bone regeneration.

The understanding of cellular energy metabolism activation by engineered scaffolds remains limited, posing challenges for therapeutic applications in tissue regeneration. This study presents biosynthesized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] and its major degradation product, 3-hydroxybutyrate (3HB), as endogenous bioenergetic fuels that augment cellular anabolism, thereby facilitating the progression of human bone marrow-derived mesenchymal stem cells (hBMSCs) towards osteoblastogenesis. Our research demonstrated that 3HB markedly boosts in vitro ATP production, elevating mitochondrial membrane potential and capillary-like tube formation. Additionally, it raises citrate levels in the tricarboxylic acid (TCA) cycle, facilitating the synthesis of citrate-containing apatite during hBMSCs osteogenesis. Furthermore, 3HB administration significantly increased bone mass in rats with osteoporosis induced by ovariectomy. The findings also showed that P(3HB-co-4HB) scaffold substantially enhances long-term vascularized bone regeneration in rat cranial defect models. These findings reveal a previously unknown role of 3HB in promoting osteogenesis of hBMSCs and highlight the metabolic activation of P(3HB-co-4HB) scaffold for bone regeneration.

Microgels sense wounds' temperature, pH and glucose.

Wound healing concerns almost all bed-side related diseases. With our increasing comprehension of healing nature, the physical and chemical natures behind the wound microenvironment have been decoupled. Wound care demands timely screening and prompt diagnosis of wound complications such as infection and inflammation. Biosensor by the way of exhaustive collection, delivery, and analysis of data, becomes indispensable to arrive at an ideal healing upshot and controlling complications by capturing in-situ wound status. Electrochemical based sensors carry some potential unstable performance subjected to the electrical circuitry and power access and contamination. The colorimetric sensors are free from those concerns. We report that microsensors designed from O/W/O of capillary fluids can continuously monitor wound temperature, pH and glucose concentration. We combined three different types of microgels to encapsulate liquid crystals of cholesterol, nontoxic fuel litmus and two glucose-sensitizing enzymes. A smartphone applet was then developed to convert wound healing images to RGB of digitalizing data. The microgel dressing effectively demonstrates the local temperature change, pH and glucose levels of the wound in high resolution where a microgel is a 'pixel'. They are highly responsive, reversible and accurate. Monitoring multiple physicochemical and physiological indicators provides tremendous potential with insight into healing processing.

Leisure-time activities and disability among Chinese community-dwelling oldest old: evidence from the Chinese Longitudinal Healthy Longevity Study.

With the acceleration of population aging, disability in older adults is a growing public health problem; however, little is known about the role of specific leisure-time activities in affecting disability. This study prospectively examined the association of leisure-time activities with disability among the Chinese oldest old. A total of 14 039 adults aged 80 years or older (median age of 89.8 years) were enrolled from the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2014. Disability was defined as the presence of concurrent impairment in activities of daily living and physical performance. Cox proportional hazards models were used to estimate the associations between leisure-time activities and disability. During a mean of 4.2 years (2.7 years) of follow-up, 4487 participants developed disability. Compared with participants who never engaged in leisure-time activities, participants who engaged in almost daily activities, including gardening, keeping domestic animals or pets, playing cards or mahjong, reading books or newspapers, and watching TV or listening to the radio had a lower risk of disability, with HRs of 0.78 (0.69-0.88), 0.64 (0.58-0.70), 0.74 (0.63-0.86), 0.74 (0.65-0.84), and 0.84 (0.77-0.90), respectively. Moreover, the risk of disability gradually decreased with participation in an increasing number of those leisure-time activities (P for trend <0.001). Frequent engagement in leisure-time activities was associated with a lower risk of disability among the Chinese oldest old. This study highlights the importance of incorporating a broad range of leisure-time activities into the daily lives of older adults.

The mechanism and promising therapeutic strategy of diabetic cardiomyopathy dysfunctions: Focus on pyroptosis.

Diabetes is a major risk factor for cardiovascular diseases, and myocardial damage caused by hyperglycemia is the main cause of heart failure. However, there is still a lack of systematic understanding of myocardial damage caused by diabetes. At present, we believe that the cellular inflammatory damage caused by hyperglycemia is one of the causes of diabetic cardiomyopathy. Pyroptosis, as a proinflammatory form of cell death, is closely related to the occurrence and development of diabetic cardiomyopathy. Therefore, this paper focuses on the important role of inflammation in the occurrence and development of diabetic cardiomyopathy. From the perspective of pyroptosis, we summarize the pyroptosis of different types of cells in diabetic cardiomyopathy and its related signaling pathways. It also summarizes the treatment of diabetic cardiomyopathy, hoping to provide methods for the prevention and treatment of diabetic cardiomyopathy by inhibiting pyroptosis.

miR-148b-5p regulates hypercalciuria and calcium-containing nephrolithiasis.

Calcium-containing stones represent the most common form of kidney calculi, frequently linked to idiopathic hypercalciuria, though their precise pathogenesis remains elusive. This research aimed to elucidate the molecular mechanisms involved by employing urinary exosomal microRNAs as proxies for renal tissue analysis. Elevated miR-148b-5p levels were observed in exosomes derived from patients with kidney stones. Systemic administration of miR-148b-5p in rat models resulted in heightened urinary calcium excretion, whereas its inhibition reduced stone formation. RNA immunoprecipitation combined with deep sequencing identified miR-148b-5p as a suppressor of calcitonin receptor (Calcr) expression, thereby promoting urinary calcium excretion and stone formation. Mice deficient in Calcr in distal epithelial cells demonstrated elevated urinary calcium excretion and renal calcification. Mechanistically, miR-148b-5p regulated Calcr through the circRNA-83536/miR-24-3p signaling pathway. Human kidney tissue samples corroborated these results. In summary, miR-148b-5p regulates the formation of calcium-containing kidney stones via the circRNA-83536/miR-24-3p/Calcr axis, presenting a potential target for novel therapeutic interventions to prevent calcium nephrolithiasis.

Association between dietary diversity changes and frailty among Chinese older adults: findings from a nationwide cohort study.

BACKGROUND: Dietary diversity has been suggested as a potential preventive measure against frailty in older adults, but the effect of changes in dietary diversity on frailty is unclear. This study was conducted to examine the association between the dietary diversity score (DDS) and frailty among older Chinese adults. METHODS: A total of 12,457 adults aged 65 years or older were enrolled from three consecutive and nonoverlapping cohorts from the Chinese Longitudinal Healthy Longevity Survey (the 2002 cohort, the 2005 cohort, and the 2008 cohort). DDS was calculated based on nine predefined food groups, and DDS changes were assessed by comparing scores at baseline and the first follow-up survey. We used 39 self-reported health items to assess frailty. Cox proportional hazard models were performed to examine the association between DDS change patterns and frailty. RESULTS: Participants with low-to-low DDS had the highest frailty incidence (111.1/1000 person-years), while high-to-high DDS had the lowest (41.1/1000 person-years). Compared to the high-to-high group of overall DDS pattern, participants in other DDS change patterns had a higher risk of frailty (HRs ranged from 1.25 to 2.15). Similar associations were observed for plant-based and animal-based DDS. Compared to stable DDS changes, participants with an extreme decline in DDS had an increased risk of frailty, with HRs of 1.38 (1.24, 1.53), 1.31 (1.19, 1.44), and 1.29 (1.16, 1.43) for overall, plant-based, and animal-based DDS, respectively. CONCLUSIONS: Maintaining a lower DDS or having a large reduction in DDS was associated with a higher risk of frailty among Chinese older adults. These findings highlight the importance of improving a diverse diet across old age for preventing frailty in later life.

Sarcopenia is attenuated by mairin in SAMP8 mice via the inhibition of FAPs fibrosis through the AMPK-TGF-ß-SMAD axis.

Sarcopenia has become a prominent health problem among the elderly because of its adverse consequence, including physical disabilities and death. Fibro-adipogenic progenitors (FAPs) exhibit adipogenic and fibrogenic potencies and regulate skeletal muscle development, which plays important role in sarcopenia. Mairin, as an ingredient of Astragalus membranaceus, has the effect of anti-fibrosis. Therefore, we predicted that mairin targeted the fibrosis of FAPs and then affected sarcopenia. To verify our ideas, mairin (30 mg/kg/day or 60 mg/kg/day) was given to senescence accelerated mouse-prone 8 (SAMP8) mice by oral administration. Aging led to loss of weight, skeletal muscle mass, strength, and function, and an increase in muscle atrophy and fibrosis, while mairin administration inhibited physiological decline caused by aging. Similarly, mairin (20 µM or 40 µM) treatment enhanced FAP proliferation but blocked the differentiation into fibroblasts. Mechanically, mairin played an anti-fibrotic role via AMP-activated protein kinase-transforming growth factor beta-drosophila mothers against decapentaplegic protein (AMPK-TGF-ß-SMAD) axis, as evidenced by increased phosphorylation of AMPKα and decreased TGF-ß and phosphorylated-SMAD2/3. In addition, the potential target genes of mairin were explored by mRNA sequencing in our study. In conclusion, mairin may interfere with the AMPK/TGF-ß/SMAD pathway to repress the fibrosis of FAPs and eventually ameliorate sarcopenia.

Lipid-associated macrophages for osimertinib resistance and leptomeningeal metastases in NSCLC.

Leptomeningeal metastases (LMs) remain a devastating complication of non-small cell lung cancer (NSCLC), particularly following osimertinib resistance. We conducted single-cell RNA sequencing on cerebrospinal fluid (CSF) from EGFR-mutant NSCLC with central nervous system metastases. We found that macrophages of LMs displayed functional and phenotypic heterogeneity and enhanced immunosuppressive properties. A population of lipid-associated macrophages, namely RNASE1_M, were linked to osimertinib resistance and LM development, which was regulated by Midkine (MDK) from malignant epithelial cells. MDK exhibited significant elevation in both CSF and plasma among patients with LMs, with higher MDK levels correlating to poorer outcomes in an independent cohort. Moreover, MDK could promote macrophage M2 polarization with lipid metabolism and phagocytic function. Furthermore, malignant epithelial cells in CSF, particularly after resistance to osimertinib, potentially achieved immune evasion through CD47-SIRPA interactions with RNASE1_M. In conclusion, we revealed a specific subtype of macrophages linked to osimertinib resistance and LM development, providing a potential target to overcome LMs.

Down-regulation of PCBP2 Suppresses the Invasion and Migration of Trophoblasts via the WNT5A/ROR2 Pathway in Preeclampsia.

Impaired extravillous trophoblast (EVT) invasion and resulted poor placentation play a vital role in the development of preeclampsia (PE). However, the underlying mechanisms of dysregulated EVTs remain unclear. This study aimed to explore the role of poly (C)-binding protein 2 (PCBP2), a multifunctional RNA binding protein, in the pathogenesis of PE and to investigate the detailed signaling pathway. Using qRT-PCR, western blot, and immunohistochemistry, we confirmed that the expression of PCBP2 significantly decreased in placentas from 18 early-onset PE and 30 late-onset PE in comparison to those from 30 normotensive pregnancies. Besides, more significant suppression of PCBP2 was observed in the early-onset type. After transfection of HTR-8/SVneo with small interfering RNA (siRNA) specific to PCBP2, the cellular biological behaviors including vitality, immigration, invasiveness, and apoptosis were evaluated by CCK-8 assay, wound-healing assay, transwell assay, and flow cytometry respectively. RNA-seq was applied to screen differentially expressed genes (DEGs) in HTR-8/SVneo upon PCBP2 silencing. GO and KEGG analysis indicated that WNT signaling pathway and the related processes such as extracellular matrix remodeling and cell adhesion were among the most enriched pathways or processes. Meanwhile, the alternative splicing of WNT5A regulated by PCBP2 was also identified by RIP-seq. Based on HTR-8/SVneo and villous explant, the regulatory roles of PCBP2 on trophoblast were confirmed to be mediated by WNT5A. Besides, it revealed that ROR2/JNK/MMP2/9 pathway was a vital pathway downstream WNT5A in trophoblast cells. In conclusion, this study suggests that down-regulated PCBP2 impaired the functions of EVTs via suppression of WNT5A-mediating ROR2/JNK/MMPs pathway, which may eventually contribute to the development of PE.

The Impact of the Cost of Travel Time and Feedback Type on Green Travel.

Green travel is a special type of pro-environmental behavior, which requires people to pay a time cost to reduce carbon emissions. This study explored the impact of the cost of travel time and feedback types on green travel. To verify the change of travel choice under different time costs, experiment 1 explored the impact of different costs of travel time on green travel. The results showed that with the increase in time cost, green travel behavior gradually decreased. This suggests that time costs can hinder green travel behavior. To intervene in this negative effect, experiment 2 explored the effects of different types of feedback intervention. The results showed that both environmental and health feedback could only intervene with green travel behavior when the time costs were low. This indicates that health and environmental feedback can intervene in the negative effects of travel time cost, but the cost range of the intervention is limited. This study has implications for promoting green travel behavior.

Circulating miRNA-21 as a diagnostic biomarker for acute coronary syndrome: a systematic review and meta-analysis of diagnostic test accuracy study.

Background: Both early detection and treatment for acute coronary syndrome (ACS) have positively affected prognosis. A microRNA, miRNA-21 (miR-21), may have additional diagnostic potential for ACS among the others. This systematic review and meta-analysis aimed to evaluate the potential role of miR-21 in identifying ACS. Methods: PubMed, EMBASE and CENTRAL databases were searched up to March 17, 2024, for case-control and cohort studies assessing the diagnostic value of circulating miR-21 in patients with ACS. The search was limited to studies published in either English or Chinese. The primary outcome was the discriminative ability to circulate miR-21 for ACS, represented by the area under the standard receiver operating characteristic curve (AUC) analysis. Meta-analyses combined the AUCs using a random-effects model. Heterogeneity among the studies was detected by the I2 and Q statistics. The quality of the studies included was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Publication bias analysis was assessed constructing by the Egger's test (PROSPERO: CRD42020209424). Results: Eleven case-control studies containing a total of 2,413 subjects with 1,236 ACS cases and 1,177 controls were included. The mean age of participants in these studies ranges between 51.0 and 69.0 years. The meta-analysis showed an overall pooled AUC of 0.779 [95% confidence interval (CI): 0.715-0.843], with high heterogeneity noted between the studies (Q statistic =190.64, I2=94.23%, P<0.001). In subgroup analyses according to the subtypes of ACS, a pooled AUC of 0.767 (95% CI: 0.648-0.887) was derived from the studies focused on acute myocardial infarction cases only. The pooled AUC for unstable angina was 0.770 (95% CI: 0.718-0.822). In subgroup analyses according to the types of control groups, pooled AUC for ACS versus healthy controls was 0.779 (95% CI: 0.715-0.843), whereas the pooled AUC for ACS versus unhealthy controls was 0.740 (95% CI: 0.645-0.836). The quality assessment showed that the studies' overall quality was moderate. No evidence of publication bias was noted (P=0.49). Conclusions: Circulating miR-21 shows abilities to differentiate between ACS and non-ACS, suggesting its potential as a novel diagnostic biomarker for ACS. However, the evidence is weakened by high heterogeneity observed among the studies. Further research is essential before it can be applied in clinical practice.

Identification of a major QTL underlying sugar content in peanut kernels based on the RIL mapping population.

High sugar content in peanut seeds is one of the major breeding objectives for peanut flavor improvement. In order to explore the genetic control of sugar accumulation in peanut kernels, we constructed a recombinant inbred line population of 256 F2:6-7 lines derived from the Luhua11 × 06B16 cross. A high-resolution genetic map was constructed with 3692 bin markers through whole genome re-sequencing. The total map distance was 981.65 cM and the average bin marker distance was 0.27cM. A major stable QTL region (qSCB09/qSSCB09) was identified on linkage group (LG) B09 associated with both sucrose content (SC) and soluble sugar content (SSC) explaining 21.51-33.58% phenotypic variations. This major QTL region was consistently detected in three environments and mapped within a physical interval of 1.56 Mb on chromosome B09, and six candidate genes were identified. These results provide valuable information for further map-based cloning of favorable allele for sugar content in peanut.

Effect of Meal-Timing on the Association of Unsaturated Fatty Acids with All-Cause and Cardiovascular Mortality among Adults: A Prospective Cohort Study with 10-Year Follow-Up.

BACKGROUND: Conflicting results have been reported on the association of dietary unsaturated fatty acids (UFAs) with longevity and cardiovascular health. Most previous studies have focused only on the amount of UFAs consumed, not the timing of intake. METHODS: This prospective cohort study used data from 30,136 adults aged 18 years and older. Intakes of UFAs by meal time and types were assessed by a 24-h dietary recall for two days. The covariate-adjusted survey-weighted Cox proportional hazards models were performed to evaluate the associations of dietary total unsaturated fatty acid (TUFA), polyunsaturated fatty acid (PUFA), and monounsaturated fatty acid (MUFA) intakes throughout the day and three meals with mortality. RESULTS: During a median of 10.0 years of follow-up, 4510 total deaths occurred. All-cause mortality decreased with increasing intakes at dinner of TUFA (HR: 0.87 [0.77-0.98]), PUFA (HR: 0.81 [0.73-0.91]), and MUFA (HR: 0.88 [0.77-0.99]). With an increased intake of PUFA at dinner, CVD mortality showed a decreasing trend. However, the inverted L-shaped non-linear trend in all-cause mortality was found with increasing intake at breakfast of TUFA (HR: 1.35 [1.17-1.57], Q3 vs. Q1), PUFA (HR: 1.30 [1.13-1.50]), and MUFA (HR: 1.28 [1.13-1.45]). Meanwhile, increased breakfast intake of UFAs was associated with increased CVD and heart disease mortality. CONCLUSIONS: Meal timing influences the association of UFAs with all-cause and CVD-related mortality.