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Stem strength plays a crucial role in the growth and development of plants, as well as in their flowering and fruiting. It not only impacts the lodging resistance of crops, but also influences the ornamental value of ornamental plants. Stem development is closely linked to stem strength; however, the roles of the SPL transcription factors in the stem development of herbaceous peony (Paeonia lactiflora Pall.) are not yet fully elucidated. In this study, we obtained and cloned the full-length sequence of PlSPL14, encoding 1085 amino acids. Quantitative real-time PCR (qRT-PCR) analysis revealed that the expression level of PlSPL14 gradually increased with the stem development of P. lactiflora and was significantly expressed in vascular bundles. Subsequently, utilizing the techniques of virus-induced gene silencing (VIGS) and heterologous overexpression in tobacco (Nicotiana tabacum L.), it was determined that PlSPL14-silenced P. lactiflora had a thinner xylem thickness, a decreased stem diameter, and weakened stem strength, while PlSPL14-overexpressing tobacco resulted in a thicker xylem thickness, an increased stem diameter, and enhanced stem strength. Further screening of the interacting proteins of PlSPL14 using a yeast two-hybrid (Y2H) assay revealed an interactive relationship between PlSPL14 and PlSLR1 protein, which acts as a negative regulator of gibberellin (GA). Additionally, the expression level of PlSLR1 gradually decreased during the stem development of P. lactiflora. The above results suggest that PlSPL14 may play a positive regulatory role in stem development and act in the xylem, making it a potential candidate gene for enhancing stem straightness in plants. [ABSTRACT FROM AUTHOR]

Background: Serum vitamin D is associated with hyperuricemia. However, previous studies have been controversial, with limited focus on children and adolescents. Objective: This study aimed to examine the cross-sectional and longitudinal associations between serum vitamin D and serum uric acid (SUA) levels in children and adolescents. Methods: The cross-sectional survey comprised 4777 participants aged 6 to 18 years, while the longitudinal survey involved 1641 participants aged 6 to 12 years, all derived from an ongoing cohort study in Shenzhen, China. Restricted cubic splines were used to visualize the dose–response relationship between vitamin D and SUA and the risk of higher SUA status. Two-segment generalized linear models (GLM) and logistic models were used to assess the association between vitamin D and SUA and higher SUA status, respectively. The longitudinal analysis used GLM. Results: We observed an inverted U-shaped relationship between vitamin D and SUA (p-overall < 0.0001, p-nonlinear = 0.0002), as well as the risk of higher SUA status (p-overall = 0.0054, p-nonlinear = 0.0015), with the vitamin D inflection point at 24.31 and 21.29 ng/mL, respectively. A 10 ng/mL increment in 25(OH)D3 levels, when below 20.92 ng/mL, was associated with a 68% rise in the risk of higher SUA status (OR: 1.68, 95%CI: 1.07–2.66). Conversely, when 25(OH)D3 levels were above or equal to 20.92 ng/mL, a 10 ng/mL increment was associated with a 45% reduction risk of higher SUA status (OR: 0.55, 95%CI: 0.36–0.84). Longitudinal analysis indicated that the annual change of SUA was from −4.80 (β, 95%CI: −10.74, 1.13) to −9.00 (β, 95%CI: −15.03, −2.99) and then to −6.77 (β, 95%CI: −12.83, −0.71, p for trend = 0.0212) μmol/L when increasing the quartile of vitamin D3. Conclusions: An inverse U-shaped relationship was observed between vitamin D and SUA as well as the risk of higher SUA status. Sufficient vitamin D levels appear to play a preventative role against the age-related increase in SUA. Ensuring adequate vitamin D levels may be beneficial in improving uric acid metabolism. [ABSTRACT FROM AUTHOR]

Purpose: The Chinese Healthy Eating Index (CHEI) is a valid instrument to assess the diet quality of the Chinese population, but evidence regarding the relationship between CHEI and the risk of diabetes remains limited. We aimed to investigate the prospective association of CHEI with diabetes among Chinese adults. Methods: 1563 adults free of diabetes at baseline and with at least two survey data from 1997 to 2018 were included. Dietary information was collected by three consecutive 24-h recalls combined with household food inventory, and long-term diet quality was evaluated by the CHEI. Diabetes was defined as self-reported physician-diagnosed diabetes and/or fasting blood glucose ≥ 7.0 mmol/L, and/or HbA1c ≥ 6.5%. Cox proportional hazard models and restricted cubic spline analysis were used to estimate the associations between CHEI and diabetes. Results: During a median follow-up of 12.0 years, 192 (10.3%) participants developed new-onset diabetes. Generally, a five-point higher CHEI score was significantly associated with a 17% lower risk of diabetes (HR, 0.83; 95%CI 0.71–0.97). In stratified analysis, inverse associations between CHEI and diabetes were more vigorous in females (HR, 0.68; 95%CI 0.54–0.85) than in males (P for interaction = 0.01). In addition, there was an L-shaped association between CHEI and diabetes risk in the whole population (P for non-linearity = 0.026), while no significant non-linear association was observed in females or males, respectively. Conclusion: Our results suggested that a long-term higher-quality diet evaluated by CHEI was significantly associated with lower risks of diabetes, and the favorable associations were more pronounced among females. [ABSTRACT FROM AUTHOR]

Summary: Background: The relationship between sugar‐free beverage (SFB) intake and childhood obesity among Chinese children is unknown. Objectives: To describe the status of SFB consumption among children and adolescents in China and assess the association between SFB intake and different types of obesity. Methods: The study was based on the baseline data of an ongoing cohort project named Evaluation and Monitoring on School‐based Nutrition and Growth in Shenzhen (EMSNGS). Food frequency questionnaires were used to collect information on SFB consumption in 3227 students aged 9–17. Physical and clinical examinations were conducted by trained investigators and clinicians. Multivariable binary logistic regression models were performed to assess the association between SFB intake and general obesity, overweight/obesity, abdominal obesity, metabolically unhealthy overweight (MUOW)/metabolically unhealthy obesity (MUO). Results: The median age of the participants was 13.28 years. Among the participants, 55.2% were boys, and 66.1% were adolescents. The median SFB consumption was 16.67 mL/d. After adjusting for potential confounding factors, each 100 mL increase in daily SFB intake was associated with an increased risk of overweight/obesity (OR = 1.14; 95%CI: 1.06–1.23), abdominal obesity (OR = 1.12; 95%CI: 1.03–1.23), and MUOW/MUO (OR = 1.12; 95%CI: 1.02–1.21), respectively. Stratified analyses showed that family income may have an impact on the association between SFB intake and overweight/obesity (P for interaction = 0.021) and abdominal obesity (P for interaction = 0.031). Conclusion: SFB intake was positively associated with childhood obesity in Chinese children, particularly among individuals with high‐income families. [ABSTRACT FROM AUTHOR]

Purpose: In order to extend the application of the original octagonal Goodman–Smith fatigue limit diagram, which is commonly used for the evaluation of structure fatigue stress in engineering, a modification of it is proposed for the structure made of S355 steel (commonly used in high-speed electric multiple units (EMUs) bogie frame). Design/methodology/approach: The modification is made based on Deutscher Verband für Schweißen und verwandte Verfahren e. V. (DVS) 1612 standard and the γ-P-S-N curve, with consideration of the fatigue evaluation requirements of different survival rates and confidence levels. The verification of the modification is performed for three welded joints and for the comparison with the experimental data. Findings: The results indicate that the design survival rate, the design safety margin and the fatigue stress evaluation of welded joint types are all improved by using the modified diagram. Originality/value: There are relatively few studies on modifying octagonal Goodman–Smith fatigue limit diagram. In this paper, a modified diagram is proposed and applied in order to ensure the safety and durability of key welded structures of rail vehicles. [ABSTRACT FROM AUTHOR]

Background and aims: Childhood and adolescence are critical periods for linear growth and preventing stunting. Current evidence indicates that dietary protein intake in children and adolescents is often two to three times higher than the recommendations in many regions worldwide. However, few studies have focused on the association between high protein intake and linear growth and stunting in this population. We aim to investigate this association in children and adolescents aged 6 to 18 years in a population with relatively high protein consumption. Methods: We conducted a large cross-sectional study involving 3299 participants from Shenzhen, a modern metropolis of China. Protein intake, including total protein, animal protein, and plant protein, was evaluated by a food-frequency questionnaire and expressed as grams per kilogram of body weight per day (g·kg−1·d−1) and as a percentage of total energy intake (%E). The primary outcomes were body height and height-for-age Z score (HAZ). Generalized linear models and logistic regression analyses were employed to examine the associations between protein intake and outcomes. We also conducted stratified analyses across different genders and pubertal stages in the aforementioned associations. Results: The mean protein intake was 1.81 g·kg−1·d−1 (17% E). After adjusting for serum calcium, zinc, vitamin D3, vitamin A levels, birth outcomes, lifestyle, and parental characteristics, each standard deviation increase of 1 in protein intake (0.64 kg−1·d−1) is found to be associated with a −5.78 cm change in body height (95% CI: −6.12, −5.45) and a −0.79 change in HAZ (95% CI: −0.84, −0.74). Consistent results were observed when protein intake was expressed as %E or specifically as animal or plant protein. Moreover, the relationship between protein intake and linear growth remained consistent across genders in different pubertal stages, similar to that of the overall participants. Conclusions: Our findings highlight the potential hazards of high protein intake on linear growth in children and adolescents. Caution should be exercised when promoting increased protein consumption in children and adolescents who already have a high intake of protein. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the crucial pathogenesis for intra-hepatic and extra-hepatic diseases, especially in elderly adults. Lifestyle management may be a modifiable cost-effective measure for MAFLD prevention, but the evidence is limited. A total of 23,408 middle-aged and elderly individuals were included in a longitudinal study from 2008 to 2018. Combined lifestyle scores (range 0–6) were evaluated by BMI, smoking, drinking, diet, physical activity, and sleep. Logistic regression models were used to calculate ORs for the risks of MAFLD and specific subtypes. The mean age of participants was 61.7 years, and 44.5% were men. Compared with poor lifestyle (scores 0–2), ORs (95% CIs) of the ideal lifestyle (scores 5–6) were 0.62 (0.57–0.68) for MAFLD, 0.31 (0.28–0.34) for MAFLD with excess weight and obesity, 0.97 (0.75–1.26) for MAFLD with diabetes, and 0.56 (0.51–0.62) for MAFLD with metabolic dysregulation. Additionally, lifestyle improvement was associated with lower risks of MAFLD (OR, 0.76; 95% CI, 0.68–0.86), MAFLD with excess weight and obesity (OR, 0.72; 95% CI, 0.63–0.81), MAFLD with diabetes (OR, 0.74; 95% CI, 0.54–1.02) and MAFLD with metabolic dysregulation (OR, 0.49; 95% CI, 0.43–0.55), respectively. Our findings suggest that adherence to a combined healthy lifestyle was associated with lower risks of MAFLD, particularly in excess weight/obese individuals or those with metabolic dysregulation. [ABSTRACT FROM AUTHOR]

Herbaceous peony (Paeonia lactiflora Pall.) has emerged in the cut flower market due to its beautiful appearance. The bending flower stems caused by a lack of mechanical strength is the main problem restricting the development of the cut P. lactiflora industry. So it is of great worth to reveal the basis of stem development changes in P. lactiflora to improve its cut flower quality. Quantitative research on gene expression characteristics can provide clues for understanding their biological functions, and the screening of relatively stable expression genes is a prerequisite for the quantitative study of gene expression characteristics. Thus, it is necessary to find appropriate genes during stem development so as to analyze the qRT‒PCR results. In this study, 10 genes were screened, and these genes expressed stably in stems of different stem strengths at three different developmental stages. Then, their expressions were evaluated by RefFinder, BestKeeper, NormFinder, and GeNorm programs. The results demonstrated that γ-tubulin (γ-TUB) was the most suitable gene, followed by α-tubulin (α-TUB) and β-D-glucosidase (β-GUS), whereas histone H3 (His) was the least suitable gene. Besides, the temporal and spatial expression characteristics of PlCOMT1, the key gene concerned with the synthesis of cell wall fillers in P. lactiflora, were also used to evaluate the suitability of genes. Consequently, γ-TUB and α-TUB are the two best combinations during stem development, and their combination can be used for the stem development of P. lactiflora. These findings will provide a reference for the selection of genes related to stem development and the study of molecular mechanisms related to stem development in P. lactiflora. [ABSTRACT FROM AUTHOR]

SUMMARY: Stem strength is an important agronomic trait affecting plant lodging, and plays an essential role in the quality and yield of plants. Thickened secondary cell walls in stems provide mechanical strength that allows plants to stand upright, but the regulatory mechanism of secondary cell wall thickening and stem strength in cut flowers remains unclear. In this study, first, a total of 11 non‐redundant Paeonia lactiflora R2R3‐MYBs related to stem strength were identified and isolated from cut‐flower herbaceous peony, among which PlMYB43, PlMYB83 and PlMYB103 were the most upregulated differentially expressed genes. Then, the expression characteristics revealed that these three R2R3‐MYBs were specifically expressed in stems and acted as transcriptional activators. Next, biological function verification showed that these P. lactiflora R2R3‐MYBs positively regulated stem strength, secondary cell wall thickness and lignin deposition. Furthermore, yeast‐one‐hybrid and dual luciferase reporter assays demonstrated that they could bind to the promoter of caffeic acid O‐methyltransferase gene (PlCOMT2) and/or laccase gene (PlLAC4), two key genes involved in lignin biosynthesis. In addition, the function of PlLAC4 in increasing lignin deposition was confirmed by virus‐induced gene silencing and overexpression. Moreover, PlMYB83 could also act as a transcriptional activator of PlMYB43. The findings of the study propose a regulatory network of R2R3‐MYBs modulating lignin biosynthesis and secondary cell wall thickening for improving stem lodging resistance, and provide a resource for molecular genetic engineering breeding of cut flowers. [ABSTRACT FROM AUTHOR]

Glucosinolates (GSLs) are secondary plant metabolites that are enriched in rapeseed and related Brassica species, and they play important roles in defense due to their anti-nutritive and toxic properties. Here, we conducted a genome-wide association study of six glucosinolate metabolites (mGWAS) in rapeseed, including three aliphatic glucosinolates (m145 gluconapin, m150 glucobrassicanapin and m151 progoitrin), one aromatic glucosinolate (m157 gluconasturtiin) and two indole glucosinolates (m165 indolylmethyl glucosinolate and m172 4-hydroxyglucobrassicin), respectively. We identified 113 candidate intervals significantly associated with these six glucosinolate metabolites. In the genomic regions linked to the mGWAS peaks, 187 candidate genes involved in glucosinolate biosynthesis (e.g., BnaMAM1, BnaGGP1, BnaSUR1 and BnaMYB51) and novel genes (e.g., BnaMYB44, BnaERF025, BnaE2FC, BnaNAC102 and BnaDREB1D) were predicted based on the mGWAS, combined with analysis of differentially expressed genes. Our results provide insight into the genetic basis of glucosinolate biosynthesis in rapeseed and should facilitate marker-based breeding for improved seed quality in Brassica species. [ABSTRACT FROM AUTHOR]

Background and Aims The tree peony (Paeonia suffruticosa Andr.) has been widely cultivated as a field plant, and petal blotch is one of its important traits, which not only promotes proliferation but also confers high ornamental value. However, the regulatory network controlling blotch formation remains elusive owing to the functional differences and limited conservation of transcriptional regulators in dicots. Methods We performed phylogenetic analysis to identify MYB44-like transcription factors in P. suffruticosa blotched cultivar 'High noon' petals. A candidate MYB44-like transcription factor, PsMYB44, was analysed via expression pattern analysis, subcellular localization, target gene identification, gene silencing in P. suffruticosa petals and heterologous overexpression in tobacco. Key Results A blotch formation-related MYB44-like transcription factor, PsMYB44, was cloned. The C-terminal of the PsMYB44 amino acid sequence had a complete C2 motif that affects anthocyanin biosynthesis, and PsMYB44 was clustered in the MYB44-like transcriptional repressor branch. PsMYB44 was located in the nucleus, and its spatial and temporal expression patterns were negatively correlated with blotch formation. Furthermore, a yeast one-hybrid assay showed that PsMYB44 could target the promoter of the late anthocyanin biosynthesis-related dihydroflavonol-4-reductase (DFR) gene, and a dual-luciferase assay demonstrated that PsMYB44 could repress PsDFR promoter activity. On the one hand, overexpression of PsMYB44 significantly faded the red colour of tobacco flowers and decreased the anthocyanin content by 42.3 % by downregulating the expression level of the tobacco NtDFR gene. On the other hand, PsMYB44 -silenced P. suffruticosa petals had a redder blotch colour, which was attributed to the fact that silencing PsMYB44 redirected metabolic flux to the anthocyanin biosynthesis branch, thereby promoting more anthocyanin accumulation in the petal base. Conclusion These results demonstrated that PsMYB44 negatively regulated the biosynthesis of anthocyanin by directly binding to the PsDFR promoter and subsequently inhibiting blotch formation, which helped to elucidate the molecular regulatory network of anthocyanin-mediated blotch formation in plants. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are identified as a non-classical way to mediate iron efflux except ferroportin. Interestingly, recent studies indicated that EVs pathway is a novel way involved in iron efflux. Mitochondria-derived vesicles (MDVs) are the potential mediator to load mitochondrial iron into EVs. Additionally, iron-replete cells resist excess iron-induced damage by secreting iron-loaded EVs, and the uptake of these EVs induces oxidative damage in the recipient cell. Importantly, iron-loaded EVs play a key role in aberrant iron distribution, which drives the progress of diseases like nonalcoholic fatty liver disease (NAFLD) and neurodegenerative diseases. Herein, we summarize extant research on intracellular iron export with an emphasis on EVs and put our eyes on the relationship between iron-loaded EVs with both parent and target cells. Iron-loaded EVs will be an important avenue for later research on their vital role in iron redistribution. [ABSTRACT FROM AUTHOR]

Paeonia ostii is an emerging woody oil crop, but the high temperature in summer is extremely unfavorable for its growth and development. Understory intercropping cultivation would provide shaded environments which could effectively reduce the ambient temperature. In order to explore whether understory intercropping cultivation would reduce the effects of high-temperature stress on P. ostii, the changes of leaf physiological indicators and leaf microstructures of sole-cropping and intercropping P. ostii were investigated. P. ostii that intercropping cultivated under Illinois pecans (Carya illinoinensis (Wangenh.) K. Koch) with 4 m × 4 m and 4 m × 8 m rowing spaces were used as samples in this study. The results showed that with continuous high temperature, the high-temperature damage index of P. ostii kept increasing, whereas the leaf relative water content continued to decline. Compared to sole-cropping, the high-temperature damage index, relative electrical conductivity, proline content, antioxidant enzymes superoxide dismutase (SOD), and ascorbate peroxidase (APX) activities of intercropping P. ostii under C. illinoinensis were significantly decreased, whereas the leaf relative water content was higher. Moreover, compared to sole-cropping, intercropping P. ostii under C. illinoinensis increased SPAD and chlorophyll contents, made mesophyll cell ultrastructures more intact, and made the chloroplasts rounder and more filled with starch granules and lipid globules, leading to enhanced photosynthesis (Pn) and transpiration rates (Tr). Notably, the reduction of high-temperature damage on intercropping P. ostii under C. illinoinensis with 4 m × 4 m rowing spaces was more significant than that under C. illinoinensis with 4 m × 8 m rowing spaces. This research provides some reference values for efficient plantation of P. ostii in the middle and lower reaches of the Yangtze River in China. [ABSTRACT FROM AUTHOR]

Cut flower quality is severely restrained by stem bending due to low stem strength. Melatonin has been shown to function in many aspects of plant growth and development, yet whether it can enhance stem strength, and the corresponding underlying mechanisms remain unclear. We investigated the role of melatonin in enhancement of stem strength in herbaceous peony (Paeonia lactiflora Pall.) by applying exogenous melatonin and changing endogenous melatonin biosynthesis. Endogenous melatonin content positively correlated with lignin content and stem strength in various P. lactiflora cultivars. Supplementation with exogenous melatonin significantly enhanced stem strength by increasing lignin content and the S/G lignin compositional ratio, up-regulating lignin biosynthetic gene expression. Moreover, overexpression of TRYPTOPHAN DECARBOXYLASE GENE (TDC) responsible for the first committed step of melatonin biosynthesis in tobacco, significantly increased endogenous melatonin, which further increased the S/G ratio and stem strength. In contrast, silencing PlTDC in P. lactiflora decreased endogenous melatonin, the S/G ratio and stem strength. Finally, manipulating the expression of CAFFEIC ACID O-METHYLTRANSFERASE GENE (COMT1), which is involved in both melatonin and lignin biosynthesis, showed even greater effects on melatonin, the S/G ratio and stem strength. Our results suggest that melatonin has a positive regulatory effect on P. lactiflora stem strength. [ABSTRACT FROM AUTHOR]

Pothos (Epipremnum aureum) is a commonly used indoor ornamental foliage, particularly in the middle and lower regions of the Yangtze River in China. It typically grows in the tropical area, and it is yet unclear whether prolonged winter temperatures cause plant damage and impact its development. In this study, the E. aureum chilling injury response was explored by maintaining it at 1 °C. Based on the acquired results, low-temperature stress (LTS) induced wilting and yellowing of leaves and diminished chloroplast pigment concentrations, particularly the chlorophyll b content. LTS also induced overproduction of reactive oxygen species (ROS) within E. aureum and enhanced the relative electrical conductivity and superoxide dismutase activity. In addition, with prolonged LTS, the anatomical structure of E. aureum was severely damaged, resulting in a marked reduction in the photochemical activity of the photosystem Ⅱ reaction center and suppressed photosynthesis. Moreover, results of the transcriptomic analysis revealed that LTS induced the expression of genes involved in the α-linolenic acid metabolic pathway, plant hormone network, host plant–pathogen association, and MAPK axis, suggesting that LTS would activate its resistant response to cold stress. These results unraveled the physiological and transcriptomical response of E. aureum to chilling injury, which would lay a theoretical foundation for the cultivation of low-temperature-tolerant varieties of E. aureum. [ABSTRACT FROM AUTHOR]

Global warming has multifarious adverse effects on plant growth and productivity. Nonetheless, the effects of endogenous phytomelatonin on the high‐temperature resistance of plants and the underlying genetic mechanisms remain unclear. Here, herbaceous peony (Paeonia lactiflora Pall.) tryptophan decarboxylase (TDC) gene involved in phytomelatonin biosynthesis was shown to respond to high‐temperature stress at the transcriptional level, and its transcript level was positively correlated with phytomelatonin production. Moreover, overexpression of PlTDC enhanced phytomelatonin production and high‐temperature stress tolerance in transgenic tobacco, while silencing PlTDC expression decreased these parameters in P. lactiflora. In addition, a 2402 bp promoter fragment of PlTDC was isolated, and DNA pull‐down assay revealed that one APETALA2/ethylene‐responsive element‐binding factor (AP2/ERF) transcription factor, PlTOE3, could specifically activate the PlTDC promoter, which was further verified by yeast one‐hybrid assay and luciferase reporter assay. PlTOE3 was a nucleus‐localized protein, and its transcript level responded to high‐temperature stress. Additionally, transgenic tobacco overexpressing PlTOE3 showed enhanced phytomelatonin production and high‐temperature stress tolerance, while silencing PlTDC expression obtained the opposite results. These results illustrated that PlTOE3 bound the PlTDC promoter to enhance high‐temperature stress tolerance by increasing phytomelatonin production in P. lactiflora. This study is to elucidate the effects of endogenous phytomelatonin on the high‐temperature resistance of plants, and the results illustrated that PlTOE3 bound the PlTDC promoter to enhance high‐temperature stress tolerance by increasing phytomelatonin production in herbaceous peony. [ABSTRACT FROM AUTHOR]

Petal blotches are commonly observed in many angiosperm families and not only influence plant–pollinator interactions but also confer high ornamental value. Tree peony (Paeonia suffruticosa Andr.) is an important cut flower worldwide, but few studies have focused on its blotch formation. In this study, anthocyanins were found to be the pigment basis for blotch formation of P. suffruticosa , and peonidin-3,5-di- O -glucoside (Pn3G5G) was the most important component of anthocyanins, while the dihydroflavonol-4-reductase gene was the key factor contributing to blotch formation. Then, the R2R3-myeloblastosis (MYB) transcription factor PsMYB30 belonging to subgroup 1 was proven as a positive anthocyanin regulator with transcriptional activation and nuclear expression. Furthermore, silencing PsMYB30 in P. suffruticosa petals reduced blotch size by 37.9%, faded blotch color and decreased anthocyanin and Pn3G5G content by 23.6% and 32.9%, respectively. Overexpressing PsMYB30 increased anthocyanin content by 14.5-fold in tobacco petals. In addition, yeast one-hybrid assays, dual-luciferase assays and electrophoretic mobility shift assays confirmed that PsMYB30 could bind to the promoter of the anthocyanin synthase (ANS) gene and enhance its expression. Altogether, a novel MYB transcription factor, PsMYB30, was identified to promote petal blotch formation by activating the expression of PsANS involved in anthocyanin biosynthesis, which provide new insights for petal blotch formation in plants. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a worldwide public health concern, mainly afflicting older adults. Although the etiology of OA remains unclear, environmental factors are increasingly considered as non-negligible risk factors. This study aims to evaluate the associations of urinary metals with OA risk and the mediated effect of biological aging.Methods: Nine urinary metal concentrations were detected among 12,584 U.S. adults based on the National Health and Nutrition Examination Survey (NHANES), including barium (Ba), cadmium (Cd), cobalt (Co), cesium (Cs), molybdenum (Mo), lead (Pb), antimony (Sb), thallium (Tl), and uranium (Tu). Multivariable logistic regression and weighted quantile sum (WQS) regression were used to explore the associations of single metal and mixed metals with OA risk, respectively. Furthermore, biological aging was measured from different perspectives, including cell senescence (telomere length) and whole-body aging (phenotypic age and biological age). Mediation analyses were conducted to investigate the mediated effects of aging on the associations of metals with OA risk.Results: In the single-exposure model, Cd, Co, and Cs were identified to be positively associated with OA risk, with odds ratios (OR) ranging from 1.48 to 1.64 (all P < 0.05). Mixed-exposure analyses showed consistent associations (OR 1.23, 95%CI 1.10 to 1.37) and highlighted that Cd, Co, and Cs were responsible for the outcomes. Additionally, Cd, Co, Cs, Pb, and Tl were positively associated with biological aging markers, while all biological aging markers had significant associations with OA risk. Further mediation analyses showed that the associations of single metal (mainly Cd and Cs) and mixed metals with OA risk parallelly mediated by the above biological aging markers, with the proportion of mediation ranging from 16.89 to 69.39% (all P < 0.05). Moreover, such associations were also serially mediated through telomere length-biological age path and telomere length-phenotypic age path (the proportion of mediation: 4.17-11.67%), indicating that metals accelerated cell senescence to lead to whole-body aging and finally aggravated OA progress.Conclusions: These findings suggested that exposure to metals increased OA risk, which was possibly and partly mediated by biological aging. [ABSTRACT FROM AUTHOR]

Herbaceous peony (Paeonia lactiflora Pall.) is an ornamental plant with huge potential in the international flower market. Similar to the flowers of most other ornamental plants, the top sellers of P. lactiflora are those with red or pink flowers. However, most studies on flower colors have focused on the novel colors and have neglected the most common red flowers. In this study, a red cultivar of P. lactiflora ('Dafugui') and a pink cultivar ('Qingwen') were selected in order to study the discrepancy in the red color of the flowers. The results demonstrate that these two cultivars have the same compositions as anthocyanins, flavones, and flavonols but different contents. 'Dafugui' was found to have a high accumulation of upstream substances due to the higher expression of the early genes encoding phenylalanine ammonialyase (PlPAL) and flavonoid 3′-hydroxylase (PlF3′H). Moreover, the anthocyanidin synthase gene (PlANS) and UDP-glucose flavonoid 3-O-glucosyltransferase gene (PlUF3GT) encoding enzymes catalyze these upstream substances into anthocyanins, resulting in more redness in 'Dafugui' than in 'Qingwen'. Our study thus provides a better understanding of the anthocyanin accumulation and coloring mechanism of P. lactiflora and can serve as a theoretical basis for breeding more red flowers using genetic engineering techniques to cater to consumers' preferences. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases, the notorious killer, are mainly caused by atherosclerosis (AS) characterized by lipids, cholesterol, and iron overload in plaques. Macrophages are effector cells and accumulate to the damaged and inflamed sites of arteries to internalize native and chemically modified lipoproteins to transform them into cholesterol-loaded foam cells. Foam cell formation is determined by the capacity of phagocytosis, migration, scavenging, and the features of phenotypes. Macrophages are diverse, and the subsets and functions are controlled by their surrounding microenvironment. Generally, macrophages are divided into classically activated (M1) and alternatively activated (M2). Recently, intraplaque macrophage phenotypes are recognized by the stimulation of CXCL4 (M4), oxidized phospholipids (Mox), hemoglobin/haptoglobin complexes [HA-mac/M(Hb)], and heme (Mhem). The pro-atherogenic or anti-atherosclerotic phenotypes of macrophages decide the progression of AS. Besides, apoptosis, necrosis, ferroptosis, autophagy and pyrotopsis determine plaque formation and cardiovascular vulnerability, which may be associated with macrophage polarization phenotypes. In this review, we first summarize the three most popular hypotheses for AS and find the common key factors for further discussion. Secondly, we discuss the factors affecting macrophage polarization and five types of macrophage death in AS progression, especially ferroptosis. A comprehensive understanding of the cellular and molecular mechanisms of plaque formation is conducive to disentangling the candidate targets of macrophage-targeting therapies for clinical intervention at various stages of AS. [ABSTRACT FROM AUTHOR]

Extensive observational and numerical simulations have been performed to better characterize the role of aerosols in affecting the clouds and precipitation. However, due to the large uncertainties of aerosol property, the effect of aerosols on clouds and precipitation over the arid and semiarid region (briefly called 'drylands') of East Asia (EA) is still unclear. Basing on observations and model simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5), we investigated the aerosol's effects on the cloud properties and precipitation over the drylands of EA from 1850 to the present and projected forward to 2,300. It is found that, during 1850–2005, with the mean aerosol optical depth (AOD) over the drylands of EA increasing, the cloud droplet number concentration (CDNC) increases, while the cloud effective droplet radius (CEDR) decreases significantly at a rate of −0.40 μm·century−1. Besides, the cloud water path (CWP) and precipitation show slightly increasing trends with the AOD increasing. Additionally, the effect of aerosols on cloud properties is saturated when the AODs reach 0.21 and 0.15 over the arid region (AR) and semiarid region (SR), respectively. According to the prediction for the period 2006–2300, the AOD and CDNC tend to decline over the drylands of EA, while the CWP, CEDR and precipitation show increasing trends. Particularly, the aerosol, clouds and precipitation indicate more significant changes over the SR in EA during 2006–2300. In future research, there is an urgent need to quantify the contribution of aerosol‐cloud interaction to the precipitation change over the drylands of EA. [ABSTRACT FROM AUTHOR]

Objectives: Senescence, characterized by permanent cycle arrest, plays an important role in diabetic nephropathy (DN). However, the mechanism of renal senescence is still unclear, and the treatment targeting it remains to be further explored. Materials and Methods: The DN mice were induced by HFD and STZ, and 3 types of renal cells were treated with high glucose (HG) to establish in vitro model. Senescence‐related and autophagy‐related markers were detected by qRT‐PCR and Western blot. Further, autophagy inhibitors and co‐immunoprecipitation were used to clarify the mechanism of CO. Additionally, the specific relationship between autophagy and senescence was explored by immunofluorescence triple co‐localization and ELISA. Results: We unravelled that senescence occurred in vivo and in vitro, which could be reversed by CO. Mechanistically, we demonstrated that CO inhibited the dysfunction of autophagy in DN mice partly through dissociating Beclin‐1‐Bcl‐2 complex. Further results showed that autophagy inhibitors blocked the improvement of CO on senescence. In addition, the data revealed that autophagy regulated the degradation of senescence‐related secretory phenotype (SASP) including Il‐1β, Il‐6, Tgf‐β and Vegf. Conclusions: These results suggested that CO protects DN mice from renal senescence and function loss via improving autophagy partly mediated by dissociating Beclin‐1‐Bcl‐2 complex, which is possibly ascribed to the degradation of SASP. These findings bring new ideas for the prevention and treatment of DN and the regulation of senescence. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is the main pathological basis for the development of cardio-cerebrovascular diseases. Abnormal accumulation of apoptotic and necrotic cells resulted in plaque enlargement, necrotic core formation and plaque rupture in AS. Under physiological conditions, apoptotic cells (ACs) could be effectively phagocytized and cleared by phagocyte-mediated efferocytosis. In contrast, the clearance efficiency of ACs in AS plaque was much lower because of the impaired efferocytosis in AS. Recent findings have made great progress on the molecular mechanisms of efferocytosis process and dynamic regulation, and its dysfunction on organismal health. Yet, there are still few effective treatments for this process. This article reviews the mechanism of efferocytosis and the role of efferocytosis in AS, highlighting a novel therapeutic strategy for AS, which mainly prevents the progression of plaque by targeting efferocytosis. [ABSTRACT FROM AUTHOR]

Stem bending caused by mechanical failure is a major constraint for high-quality herbaceous peony (Paeonia lactiflora Pall.) cut flowers, but little is known about the underlying factors. In this study, two P. lactiflora cultivars, Xixia Yingxue (bending) and Hong Feng (upright), were used to investigate differences in stem bending. The results showed that the stem mechanical strength of Hong Feng was significantly higher than that of Xixia Yingxue, and the thickening of the secondary cell wall and the number of thickened secondary cell wall layers in Hong Feng were significantly higher than those in Xixia Yingxue. Moreover, compared with Xixia Yingxue, Hong Feng showed greater lignification of the cell wall and lignin deposition in the cell walls of the sclerenchyma, vascular bundle sheath and duct. All three types of lignin monomers were detected. The S-lignin, G-lignin, and total lignin contents and the activities of several lignin biosynthesis-related enzymes were higher in Hong Feng than in the other cultivar, and the S-lignin content was closely correlated with stem mechanical strength. In addition, 113,974 full-length isoforms with an average read length of 2106 bp were obtained from the full-length transcriptome of P. lactiflora stems, and differential expression analysis was performed based on the comparative transcriptomes of these two cultivars. Ten lignin biosynthesis-related genes, including 26 members that were closely associated with lignin content, were identified, and multiple upregulated and downregulated transcription factors were found to positively or negatively regulate lignin biosynthesis. Consequently, lignin was shown to provide mechanical support to P. lactiflora stems, providing useful information for understanding the formation of P. lactiflora stem strength. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Elevated serum cancer antigen 19‐9 (CA19‐9) levels have been found in diabetes patients in most observational studies; however, whether there is a causal association between CA19‐9 and diabetes mellitus is unclear. Materials and Methods: Our study was carried out based on the Dongfeng‐Tongji cohort comprising 27,009 individuals. We first investigated the associations between serum CA19‐9 levels and incident diabetes mellitus risk in a prospective cohort study (12,700 individuals). Then, we explored the potential causal relationship between CA19‐9 and diabetes mellitus risk in a cross‐sectional study (3,349 diabetes mellitus patients and 8,341 controls) using Mendelian randomization analysis. A weighted genetic risk score was calculated by adding the CA19‐9 increasing alleles in five single‐nucleotide polymorphisms (rs17271883, rs3760776 and rs3760775 in FUT6, rs11880333 in CA11, rs265548 in B3GNT3, and rs1047781 in FUT2), which were identified in a previous genome‐wide association study on serum CA19‐9 levels. Results: In the prospective study, a total of 1,004 incident diabetes mellitus patients were diagnosed during a mean 4.54‐year follow‐up period. Elevated serum CA19‐9 level was associated with a higher incident diabetes risk after adjustment for confounders, with a hazard ratio of 1.20 (95% confidence interval 1.11–1.30) per standard deviation (12.17 U/mL) CA19‐9 increase. Using the genetic score to estimate the unconfounded effect, we did not find a causal association of CA19‐9 with diabetes risk (odds ratio per weighted CA19‐9‐increasing allele: 0.99, 95% confidence interval 0.94–1.04; P = 0.61). Conclusions: The present study did not support a causal association of serum CA19‐9 with diabetes risk. CA19‐9 might be a potential biomarker of incident diabetes mellitus risk. [ABSTRACT FROM AUTHOR]

Herbaceous peony (Paeonia lactiflora Pall.) is one of the color-leaved ornamental spring plants, with graceful appearance and splendid color. However, the underlying mechanism of this coloration variation from purple to green has not been studied in P. lactiflora. In th study, the leaves in purple, purple–green, and green stages were compared in terms of anatomical, physiological, and molecular. We found that the variation of leaf color from purple to green was mainly determined by the change in pigments distributed in the leaf surface. Physiological experiments showed a significant increase in chlorophyll contents and a notable reduction in anthocyanin contents in leaves from the purple to green stages. We further found that the anthocyanin biosynthesis-related dihydroflavonol 4-reductase (DFR) gene and anthocyanin synthase (ANS) gene as well as chlorophyll biosynthesis-related glutamyl-tRNA reductase (HEMA) gene showed a decreased trend in leaves from purple to green stages, whereas the chlorophyll degradation-related chlorophyll b reductase (NYC) gene showed a rising trend. Alteration of DFR and ANS gene expression might reduce anthocyanin accumulation, whereas increased HEMA gene expression would enhance chlorophyll biosynthesis and reduced NYC gene expression would inhibit chlorophyll degradation. Consequently, reduction in anthocyanins and enhanced deposition of chlorophylls resulted in leaf coloration variation from purple to green in P. lactiflora, which could improve our understanding of its mechanism for further studies. [ABSTRACT FROM AUTHOR]

Aims: Observational studies indicated that resting heart rate (RHR) was associated with diabetes mellitus (DM) risk; however, it remains unclear whether the association between RHR and DM is causal. We aimed to examine whether there was causal association of RHR with DM risk. Methods: A prospective study including 16,201 middle-aged and older Chinese (7031 males and 9170 females) derived from the Dongfeng-Tongji cohort was performed. Cox proportional hazard regression models were conducted to estimate the associations between RHR and incident DM risk. In 7481 participants, 65 single nucleotide polymorphisms related to RHR were genotyped. A genetic risk score (GRS) of RHR was calculated based on the RHR-associated variants. The causal associations of RHR with DM risk were investigated by Mendelian randomization analysis. Results: During a mean (SD) follow-up of 4.5 (0.5) years, 1110 diabetes were identified. Compared with the referential RHR group (≤ 60 beats per minute [bpm]), individuals with RHR > 80 bpm have a higher incident diabetes risk, with a hazard ratio of 1.40 (95% confidence interval [CI], 1.05–1.88). With per SD increase in the weighted genetic risk score, the resting heart rate increased by 0.71 bpm (95% CI 0.49–0.93). By using the GRS to estimate the unconfounded effect, we found that higher resting heart rate did not have a causal effect on diabetes risk (OR 1.00 [95% CI 0.95–1.05]). Conclusions: The present study supported a positive but not a causal association of RHR with incident diabetes risk. More studies are needed to verify our findings. [ABSTRACT FROM AUTHOR]

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Background: Epidemiological studies suggest that elevated serum uric acid (SUA) is associated with heightened incident kidney disease in both the general population and the type 2 diabetes (T2D) cases, although the results were not entirely consistent.Methods: We investigated prospective association between SUA levels and estimated glomerular filtration (eGFR) decline risk (eGFR <60 mL min-1 1.73 m-2 ) among 3123 T2D in the Dongfeng-Tongji cohort and further examined this association with a meta-analysis. Generalize linear model was used to assess the associations of SUA with eGFR decline in the cohort. In the meta-analysis, we used both fix-effects and random-effects models to calculate the overall effect estimate.Results: During 5-year follow-up, 303 (9.7%) patients developed eGFR decline. After multiple adjustments, the relative risk (RR) (95% CI) of eGFR decline was 1.55 (1.07, 2.26) when comparing the highest with the lowest sex-specific uric acid quartile. A 100 μmol/L increment of SUA level was significantly associated with 21% increased risk of eGFR decline. The SUA-eGFR decline association was more evident in men, but not in women. In meta-analysis, the pooled RR (95% CI) was 2.33 (1.66, 3.25) for developing eGFR decline when comparing the highest with the lowest levels of uric acid. A 100 μmol/L increment of SUA level was significantly associated with a 33% increased risk of eGFR decline.Conclusions: Our results indicate an independent and significant positive association between higher SUA and increased risk of developing eGFR decline among T2D cases. [ABSTRACT FROM AUTHOR]

Background: Emerging studies have investigated the association between different anthropometric indices with diabetes risk but the results were inconsistent. The aims of the study were to examine the associations of different anthropometric indices with incident diabetes risk and whether novel anthropometric indices improve diabetes prediction beyond traditional indices among elderly Chinese.Methods: Nine thousand nine hundred sixty-two elderly individuals (age ≥ 60 years old) derived from the prospective Dongfeng-Tongji cohort were included. Hazard ratio (HR) and corresponding 95% confidence interval (CI) were evaluated by Cox proportional hazard model to examine the associations between traditional anthropometric indices (body mass index [BMI], waist circumference [WC], waist-to-height ratio [WHtR]), novel anthropometric indices (visceral adiposity index [VAI], a body shape index [ABSI], body roundness index [BRI]) and diabetes risk. Receiver operating characteristic (ROC) curve and area under curve (AUC) were applied to compare the novel anthropometric indices with the traditional indices in diabetes prediction.Results: During mean 4.6 years of follow-up, 614 incident cases of type 2 diabetes (T2D) were identified. Significant positive associations were detected between BMI, WC, WHtR, VAI and BRI and incident T2D risk. For ABSI, no significant association was observed in either men or women. BMI was the strongest predictor in diabetes in men (AUC = 0.655) comparable with the other anthropometric indices (P < 0.05). Similar as men, BMI was the strongest predictor (AUC = 0.635) in women. Except for WC, the AUC of BMI was larger than WHtR, VAI, and BRI. In contrast, ABSI was not a good predictor in either men (AUC = 0.507) or women (AUC = 0.503).Conclusions: In elderly Chinese, BMI, WC, WHtR, VAI and BRI were positively associated with incident T2D risk. Among them, BMI was the strongest predictor in both men and women. [ABSTRACT FROM AUTHOR]

Reference 1 Zhao D., Tang Y., Xia X., Sun J., Meng J., Shang J., Tao J. Integration of Transcriptome, Proteome, and Metabolome Provides Insights into How Calcium Enhances the Mechanical Strength of Herbaceous Peony Inflorescence Stems. Due to the authors having made an error, the control group and the control (enlargement) group in S3 and the nano-CaCO SB 3 sb group and the nano-CaCO SB 3 sb (enlargement) group in S4 of Figure 7A (marked in red) need to be corrected. Integration of Transcriptome, Proteome, and Metabolome Provides Insights into How Calcium Enhances the Mechanical Strength of Herbaceous Peony Inflorescence Stems. [Extracted from the article]

Background: Whether cigarette smoking and moderate drinking are associated with non-alcoholic fatty liver disease (NAFLD)has not been fully described. This study investigated the separate and joint effects of smoking and moderate drinking on Chinese men with NAFLD. Methods: Across-sectional assay from DFTJ Cohort study was performed with a size of 9432 elderly Chinese men excluding excessive alcohol consumption (<210g/week). Fatty liver was diagnosed by standardized ultrasonographic inspection. The odds ratio (OR) of alcohol consumption and smoking for the prevalence of NAFLD were analyzed using multiple logistic regression with multiple adjustments. Results: The prevalence of NAFLD in current smokers (pack-year≥40) and drinkers (80~210g/week or drinking duration≥35years) was significantly higher than that in non-smokers and non-drinkers, respectively. The combination of current smoking (pack-year≥40) and drinking (80~210g/week) was associated with the highest risk of NAFLD (OR 1.85; 95% confidence interval [CI] 1.28–2.68;P<0.01). The similar combined effect was found in participants with pack-year≥40 and drinking duration≥35 years (OR 1.72; 95% CI 1.26–2.34;P<0.01). Moreover, an interaction was observed between current smoking and moderate drinking in NAFLD. Conclusions: In elderly Chinese men, cigarette smoking and moderate alcohol consumption exerts an evident joint effect and interaction on the prevalence of NAFLD, although both are significantly and independently associated with NAFLD prevalence. Such findings highlight particular significance of avoidance of cigarette and alcohol on NAFLD prevention. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to examine the bidirectional association between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Methods: The data was derived from the Dongfeng-Tongji cohort study, which was established in 2008 and followed until October 2013. NAFLD was classified as none, mild, moderate/severe based on ultrasound examination. The analysis to examine the association between NAFLD and incident T2DM risk included 18,111 participants free of diabetes at baseline and the duration of follow-up was 4.60 ± 0.60 years. Cox proportional regression model was used to calculate the hazard ratio (HR) for the association. The analysis to investigate the association between T2DM and incident NAFLD risk included 12,435 participants free of NAFLD at baseline. Logistic regression model was used to calculate the odd ratio (OR) of NAFLD. Results: Compared with those without NAFLD, individuals with mild or moderate/severe NAFLD had a monotonic elevated risk of developing T2DM (HR: 1.88 [95% CI: 1.63–2.18] and 2.34 [1.85–2.96], respectively) after adjustment for potential confounders. In a parallel analysis, compared to participants with fasting plasma glucose < 6.1 mmol/L, the ORs of developing NAFLD in subjects with impaired fasting glucose and T2DM were 1.35 (95% CI: 1.16–1.57) and 1.40 (95% CI: 1.22–1.62), respectively. Conclusions: Our results provide compelling evidence that the NAFLD-T2DM association is bidirectional in Chinese population. [ABSTRACT FROM AUTHOR]

Background:To examine the association between self-reported nighttime sleep duration and nonalcoholic fatty liver disease (NAFLD) risk by comparing the incidence rates of NAFLD among healthy subjects with different sleep duration during the 5 years follow-up. Methods:8965 eligible NAFLD-free subjects with a mean age of 61.6 years (males, 43.4%) from Dongfeng-Tongji cohort study at baseline were enrolled in the study. Logistic regression analysis was used to estimate the association between sleep duration and incident NAFLD with potential confounders adjusted. Sleep duration was categorized into five groups: <6 h, 6–7 h, 7–8 h, 8–9 h, ≥9 h. Result:During the 5-years of follow-up, a total of 2,197 participants were newly diagnosed as NAFLD. Compared with those reported 7–8 h per day of nighttime sleep, the multivariable-adjusted odds ratio (95% confidence intervals) were 1.21 (1.07–1.38) for those who sleep 8–9 h/day, and 1.31 (1.13–1.52) for those who sleep over 9 h/day. However, no significant association was found with short nightly sleep duration (<7 h/day). Conclusion:Long nighttime sleep duration was associated with a modestly increased risk of NAFLD in a middle-aged and elderly Chinese population. Key messagesLong nighttime sleep duration was associated with a modestly increased risk of NAFLD in a middle-aged and elderly Chinese population.The effect of long nighttime sleep on the risk of incident NAFLD was attenuated greatly by body mass index (BMI) in men. [ABSTRACT FROM PUBLISHER]

Introduction: Oxidative stress plays a pivotal role in the intense exercise-induced myocardium injury, and mitochondrial compartment is presumed as the main source and susceptible target of intracellular reactive oxygen species (ROS). Purpose: The objective of this study was to evaluate the protective effect of quercetin, a naturally occurring flavonoids possessing antioxidant effect on repeated intense exercise-induced mitochondrial oxidative stress and dysfunction. Methods: Adult male BALB/C mice were treated by quercetin (100 mg/kg bw) for 4 weeks and subjected to the exercise protocol on a treadmill (28 m/min at 5° slope for 90 min) for seven consecutive days concurrently at the fourth week. Results: Intense exercise in mice resulted in the leakage of creatine kinase-MB (increased from 221.5 ± 33.8 to 151.1 ± 19.1 U/l, P < 0.01) and ultrastructural malformation mainly evidenced by disrupted myofibrils and swollen mitochondria, which was overtly attenuated by quercetin prophylaxis. Quercetin pretreatment evidently alleviated mitochondrial oxidative stress by inhibiting glutathione depletion and aconitase inactivation, ROS over-generation, and lipid peroxidation in cardiac mitochondria of intense exercise mice. Furthermore, mitochondrial dysfunction manifested by decreased mitochondrial membrane potential (68.6 ± 7.6 versus 100.0 ± 7.7 %, P < 0.01) and respiratory control ratio (5.03 ± 0.55 versus 7.48 ± 0.71, P < 0.01) induced as a consequence of acute exercise was markedly mitigated by quercetin precondition. Conclusion: Quercetin protects mouse myocardium against intense exercise injury, especially ultrastructural damage and mitochondrial dysfunction, probably through its beneficial antioxidative effect, highlighting a promising strategy for over-training injury by naturally occurring phytochemicals. [ABSTRACT FROM AUTHOR]

(1) Background: Pancreatic iron deposition has been found in the progression of type 2 diabetes (T2DM); however, whether ferroptosis contributes to the dysfunction of pancreatic β cells (PBC) remains enigmatic. Moreover, the potential protective effect of quercetin is also elusive; (2) Methods: T2DM mice model was established by multiple low dose streptozocin (STZ) injection, after which quercetin was intervened for 4 months; (3) Results: Substantially normalized glucose tolerance, diabetic symptoms, homeostasis model assessment for insulin resistance (HOMA-IR), and homeostasis model assessment for β cell (HOMA-β) index in comparison with the findings of T2DM control. Distorted pancreatic islets and especially shrunken mitochondria with cristae loss in PBC were observed in T2DM mice, which was ameliorated by quercetin. Meanwhile, quercetin lowered the iron level particularly in the islet in T2DM mice. In spite of compensatory xCT up-regulation, T2DM molding depleted glutathione (GSH), down-regulated glutathione peroxidase 4 (GPX4), and induced oxidative stress in pancreatic tissue, which was abolished partially by quercetin. More importantly, insulin secretion was worsened by ferroptosis-inducing erastin or RAS-selective lethal compounds 3 (RSL-3). Quercetin, ferroptosis inhibitor ferrostatin-1 and iron-chelating deferoxamine, rescued cell viability when cells were challenged with high-glucose; (4) Conclusions: Our findings identify that ferroptosis contributes to the PBC loss and dysfunction. Quercetin exerts beneficial effects on T2DM potentially by inhibiting pancreatic iron deposition and PBC ferroptosis, highlighting promising control strategies of T2DM by quercetin. [ABSTRACT FROM AUTHOR]