OsMAPK6 phosphorylation and CLG1 ubiquitylation of GW6a non-additively enhance rice grain size through stabilization of the substrate.

The chromatin modifier GRAIN WEIGHT 6a (GW6a) enhances rice grain size and yield. However, little is known about its gene network determining grain size. Here, we report that MITOGEN-ACTIVED PROTEIN KINASE 6 (OsMAPK6) and E3 ligase CHANG LI GENG 1 (CLG1) interact with and target GW6a for phosphorylation and ubiquitylation, respectively. Unexpectedly, however, in vitro and in vivo assays reveal that both of the two post-translational modifications stabilize GW6a. Furthermore, we uncover two major GW6a phosphorylation sites (serine142 and threonine186) targeted by OsMAPK6 serving an important role in modulating grain size. In addition, our genetic and molecular results suggest that the OsMAPK6-GW6a and CLG1-GW6a axes are crucial and operate in a non-additive manner to control grain size. Overall, our findings identify a previously unknown mechanism by which phosphorylation and ubiquitylation non-additively stabilize GW6a to enhance grain size, and reveal correlations and interactions of these posttranslational modifications during rice grain development.

[Effects of Pesticides Use on Pesticides Residues and Its Environmental Risk Assessment in Xingkai Lake（China）].

Xingkai Lake, located in Heilongjiang Province, is an important fishery and agricultural base and is seriously polluted by agricultural non-point sources. To clarify the residual status of many pesticides in the surface water of Xingkai Lake, 27 types of pesticides, herbicides, and their degradation products were analyzed in rice paddy, drainage, and surface water around Xingkai Lake (China) during the rice heading and maturity periods. The results showed that all 27 types of pesticides, herbicides, and their degradation products were detected during the rice heading period, and the total concentration ranged from 247.97 to 6 094.49 ng·L-1. Additionally, 25 species were detected during the rice maturity period, and the total concentration ranged from 485.36 to 796.23 ng·L-1. In comparison, more pesticides, herbicides, and derived degradation products were detected during the heading period, and their total concentration was higher as well. During the rice heading period, atrazine, simetryn, and paclobutrazol were the main detected pesticides, atrazine and isoprothiolane were the main pesticides detected during the maturity period. The distribution characteristics of pesticides and herbicides in the surface water around Xingkai Lake (China) was similar to that in drainage, so they were probably imported from the drainage and rice paddy. The average risk quotient (RQ) values of atrazine, simetryn, prometryn, butachlor, isoprothiolane, and oxadiazon were higher than 0.1 in drainage and Xingkai Lake (China), which showed a potential risk to aquatic organisms.

Optimizing rice grain size by attenuating phosphorylation-triggered functional impairment of a chromatin modifier ternary complex.

Histone acetylation affects numerous cellular processes, such as gene transcription, in both plants and animals. However, the posttranslational modification-participated regulatory networks for crop-yield-related traits are largely unexplored. Here, we characterize a regulatory axis for controlling rice grain size and yield, centered on a potent histone acetyltransferase (chromatin modifier) known as HHC4. HHC4 interacts with and forms a ternary complex with adaptor protein ADA2 and transcription factor bZIP23, wherein bZIP23 recruits HHC4 to specific promoters, and ADA2 and HHC4 additively enhance bZIP23 transactivation on target genes. Meanwhile, HHC4 interacts with and is phosphorylated by GSK3-like kinase TGW3. The resultant phosphorylation triggers several functional impairments of the HHC4 ternary complex. In addition, we identify two major phosphorylation sites of HHC4 by TGW3-sites which play an important role in controlling rice grain size. Overall, our findings thus have critical implications for understanding epigenetic basis of grain size control and manipulating the knowledge for higher crop productivity.

Mendelian randomization evidence for the causal effects of socio-economic inequality on human longevity among Europeans.

Human longevity correlates with socio-economic status, and there is evidence that educational attainment increases human lifespan. However, to inform meaningful health policies, we need fine-grained causal evidence on which dimensions of socio-economic status affect longevity and the mediating roles of modifiable factors such as lifestyle and disease. Here we performed two-sample Mendelian randomization analyses applying genetic instruments of education, income and occupation (n = 248,847 to 1,131,881) to estimate their causal effects and consequences on parental lifespan and self-longevity (n = 28,967 to 1,012,240) from the largest available genome-wide association studies in populations of European ancestry. Each 4.20 years of additional educational attainment were causally associated with a 3.23-year-longer parental lifespan independently of income and occupation and were causally associated with 30-59% higher odds of self-longevity, suggesting that education was the primary determinant. By contrast, each one-standard-deviation-higher income and one-point-higher occupation was causally associated with 3.06-year-longer and 1.29-year-longer parental lifespans, respectively, but not independently of the other socio-economic indicators. We found no evidence for causal effects of income or occupation on self-longevity. Mediation analyses conducted in predominantly European-descent individuals through two-step Mendelian randomization suggested that among 59 candidates, cigarettes per day, body mass index, waist-to-hip ratio, hypertension, coronary heart disease, myocardial infarction, stroke, Alzheimer's disease, type 2 diabetes, heart failure and lung cancer individually played substantial mediating roles (proportion mediated, >10%) in the effect of education on specific longevity outcomes. These findings inform interventions for remediating longevity disparities attributable to socio-economic inequality.

Control of grain size in rice by TGW3 phosphorylation of OsIAA10 through potentiation of OsIAA10-OsARF4-mediated auxin signaling.

Grain size is a key component of grain yield and quality in crops. Several core players of auxin signaling have been revealed to modulate grain size; however, to date, few genetically defined pathways have been reported, and whether phosphorylation could boost degradation of Aux/IAA proteins is uncertain. Here, we show that TGW3 (also called OsGSK5) interacts with and phosphorylates OsIAA10. Phosphorylation of OsIAA10 facilitates its interaction with OsTIR1 and subsequent destabilization, but this modification hinders its interaction with OsARF4. Our genetic and molecular evidence identifies an OsTIR1-OsIAA10-OsARF4 axis as key for grain size control. In addition, physiological and molecular studies suggest that TGW3 mediates the brassinosteroid response, the effect of which can be relayed through the regulatory axis. Collectively, these findings define a auxin signaling pathway to regulate grain size, in which phosphorylation of OsIAA10 enhances its proteolysis and potentiates OsIAA10-OsARF4-mediated auxin signaling.

Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Metabolomics-based comparative analysis of the effects of host and environment on Viscum coloratum metabolites and antioxidative activities.

Viscum coloratum (Kom.) Nakai is a well-known medicinal hemiparasite widely distributed in Asia. The synthesis and accumulation of its metabolites are affected by both environmental factors and the host plants, while the latter of which is usually overlooked. The purpose of this study was to comprehensively evaluate the effects of host and habitat on the metabolites in V. coloratum through multiple chemical and biological approaches. The metabolite profile of V. coloratum harvested from three different host plants in two habitats were determined by multiple chemical methods including high-performance liquid chromatography-ultraviolet (HPLC-UV), gas chromatography-flame ionization detector (GC-FID) and ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF/MS). The differences in antioxidant efficacy of V. coloratum were determined based on multiple in vitro models. The multivariate statistical analysis and data fusion strategy were applied to analyze the differences in metabolite profile and antioxidant activity of V. coloratum. Results indicated that the metabolite profile obtained by various chemical approaches was simultaneously affected by host and environment factors, and the environment plays a key role. Meanwhile, three main differential metabolites between two environment groups were identified. The results of antioxidant assay indicated that the environment has greater effects on the biological activity of V. coloratum than the host. Therefore, we conclude that the integration of various chemical and biological approaches combined with multivariate statistical and data fusion analysis, which can determine the influences of host plant and habitat on the metabolites, is a powerful strategy to control the quality of semi-parasitic herbal medicine.

Major osteoporosis fracture prediction in type 2 diabetes: a derivation and comparison study.

The widely recommended fracture prediction tool FRAX was developed based on and for the general population. Although several adjusted FRAX methods were suggested for type 2 diabetes (T2DM), they still need to be evaluated in T2DM cohort. INTRODUCTION: This study was undertaken to develop a prediction model for Chinese diabetes fracture risk (CDFR) and compare its performance with those of FRAX. METHODS: In this retrospective cohort study, 1730 patients with T2DM were enrolled from 2009.08 to 2013.07. Major osteoporotic fractures (MOFs) during follow-up were collected from Electronic Health Records (EHRs) and telephone interviews. Multivariate Cox regression with backward stepwise selection was used to fit the model. The performances of the CDFR model, FRAX, and adjusted FRAX were compared in the aspects of discrimination and calibration. RESULTS: 6.3% of participants experienced MOF during a median follow-up of 10 years. The final model (CDFR) included 8 predictors: age, gender, previous fracture, insulin use, diabetic peripheral neuropathy (DPN), total cholesterol, triglycerides, and apolipoprotein A. This model had a C statistic of 0.803 (95%CI 0.761-0.844) and calibration χ2 of 4.63 (p = 0.86). The unadjusted FRAX underestimated the MOF risk (calibration χ2 134.5, p < 0.001; observed/predicted ratio 2.62, 95%CI 2.17-3.08), and there was still significant underestimation after diabetes adjustments. Comparing FRAX, the CDFR had a higher AUC, lower calibration χ2, and better reclassification of MOF. CONCLUSION: The CDFR model has good performance in 10-year MOF risk prediction in T2DM, especially in patients with insulin use or DPN. Future work is needed to validate our model in external cohort(s).

A multiomic study uncovers a bZIP23-PER1A-mediated detoxification pathway to enhance seed vigor in rice.

Seed vigor in crops is important in terms of improving grain quality and germplasm conservation; however, little is known about its regulatory mechanisms through the encoded proteome and gene network. Comparative analyses of transcriptome (RNA sequencing [RNA-seq]) and broadly targeted metabolic profiling of two subspecific rice cultivars with distinct seed vigor during accelerated aging revealed various biological pathways and metabolic processes as key influences explaining trait differences. RNA-seq coexpression regulatory network analyses identified several transcription factors, including bZIP23 and bZIP42, that act as nodes in the gene network. Importantly, transgenic seeds of overexpression of bZIP23 enhanced seed vigor, whereas its gene knockout reduced seed vigor, suggesting that the protein it encodes functions as a positive regulator. Similarly, overexpression and knockout of PER1A that encodes a key player in the detoxification pathway enhanced and decreased seed vigor, respectively. We further demonstrated a direct interaction of the PER1A promoter with bZIP23 in seeds, which activates the expression of PER1A, and the genetic evidence suggested that bZIP23 most likely functions in a common pathway with and acts upstream of PER1A to modulate seed vigor. In addition, the control of seed vigor by the bZIP23-PER1A module was connected with that of the abscisic acid signaling pathway. Collectively, we revealed the genetic architecture of variation in seed vigor and uncovered the bZIP23-PER1A-mediated detoxification pathway that enhances the trait in rice.

Association between the Neutrophil-to-lymphocyte Ratio and New-onset Subclinical Macrovascular and Microvascular Diseases in the Chinese Population.

OBJECTIVE: The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population. METHODS: From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria. RESULTS: During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI ( P for interaction: 0.01). CONCLUSION: NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.

The ubiquitin-interacting motif-type ubiquitin receptor HDR3 interacts with and stabilizes the histone acetyltransferase GW6a to control the grain size in rice.

For grain crops such as rice (Oryza sativa), grain size substantially affects yield. The histone acetyltransferase GRAIN WEIGHT 6a (GW6a) determines grain size and yield in rice. However, the gene regulatory network underlying GW6a-mediated regulation of grain size has remained elusive. In this study, we show that GW6a interacts with HOMOLOG OF DA1 ON RICE CHROMOSOME 3 (HDR3), a ubiquitin-interacting motif-containing ubiquitin receptor. Transgenic rice plants overexpressing HDR3 produced larger grains, whereas HDR3 knockout lines produce smaller grains compared to the control. Cytological data suggest that HDR3 modulates grain size in a similar manner to GW6a, by altering cell proliferation in spikelet hulls. Mechanistically, HDR3 physically interacts with and stabilizes GW6a in an ubiquitin-dependent manner, delaying protein degradation by the 26S proteasome. The delay in GW6a degradation results in dramatic enhancement of the local acetylation of H3 and H4 histones. Furthermore, RNA sequencing analysis and chromatin immunoprecipitation assays reveal that HDR3 and GW6a bind to the promoters of and modulate a common set of downstream genes. In addition, genetic analysis demonstrates that HDR3 functions in the same genetic pathway as GW6a to regulate the grain size. Therefore, we identified the grain size regulatory module HDR3-GW6a as a potential target for crop yield improvement.

Lgr4 promotes aerobic glycolysis and differentiation in osteoblasts via the canonical Wnt/ß-catenin pathway.

Lgr4, a G-protein-coupled receptor, is associated with various physiological and pathological processes including oncogenesis, energy metabolism, and bone remodeling. However, whether Lgr4 is involved in osteoblasts' metabolism is not clear. Here we uncover that in preosteoblast cell line, lacking Lgr4 results in decreased osteogenic function along with reduced glucose consumption, glucose uptake, and lactate production in the presence of abundant oxygen, which is referred to as aerobic glycolysis. Activating canonical Wnt/ß-catenin signaling rescued the glycolytic dysfunction. Lgr4 promotes the expression of pyruvate dehydrogenase kinase 1 (pdk1) and is abolished by interfering canonical Wnt/ß-catenin signaling. Mice lacking Lgr4 specifically in osteoblasts (Lgr4osb-/- ) exhibit decreased bone mass and strength due to reduced bone formation. Additionally, glycolysis of osteoblasts is impaired in Lgr4osb-/- mice. Our study reveals a novel function of Lgr4 in regulating the cellular metabolism of osteoblasts. © 2021 American Society for Bone and Mineral Research (ASBMR).

Proteomic Analysis of Desiccation Tolerance and Its Re-Establishment in Different Embryo Axis Tissues of Germinated Pea Seeds.

The model of loss and re-establishment of desiccation tolerance (DT) in germinated seeds has been well developed to explore the mechanisms associated with DT, but little attention has been paid to the tissue variation in this model. Herein, we investigated DT in different embryo axis tissues of germinated pea seeds and its re-establishment by poly(ethylene glycol) (PEG) treatment and then employed an iTRAQ-based proteomic method to explore the underlying mechanisms. DT varied among the four embryo axis parts of germinated seeds: epicotyl > hypocotyl-E (hypocotyl part attached to the epicotyl) > hypocotyl-R (hypocotyl part attached to the radicle) > radicle. Meanwhile, PEG treatment of germinated seeds resulted in a differential extent of DT re-establishment in these tissues. Proteins involved in detoxification and stress response were enriched in desiccation-tolerant hypocotyls-E and epicotyls of germinated seeds, respectively. Upon rehydration, proteome change during dehydration was recovered in the hypocotyls-E but not in the radicles. PEG treatment of germinated seeds led to numerous changes in proteins, in abundance in desiccation-sensitive radicles and hypocotyls-R, of which many accumulated in the hypocotyls-E and epicotyls before the treatment. We hypothesized that accumulation of groups 1 and 5 LEA proteins and proteins related to detoxification, ABA, ethylene, and calcium signaling contributed mainly to the variation of DT in different tissues and its re-establishment.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.

OBJECTIVE: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. METHODS: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. RESULTS: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). CONCLUSION: An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Gut microbiota-derived propionate mediates the neuroprotective effect of osteocalcin in a mouse model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with no absolute cure. The evidence of the involvement of gut microbiota in PD pathogenesis suggests the need to identify certain molecule(s) derived from the gut microbiota, which has the potential to manage PD. Osteocalcin (OCN), an osteoblast-secreted protein, has been shown to modulate brain function. Thus, it is of interest to investigate whether OCN could exert protective effect on PD and, if yes, whether the underlying mechanism lies in the subsequent changes in gut microbiota. RESULTS: The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated Bacteroidetes and depleted Firmicutes phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice. CONCLUSIONS: Together, our results demonstrate that OCN ameliorates motor deficits and dopaminergic neuronal loss in PD mice, modulating gut microbiome and increasing propionate level might be an underlying mechanism responsible for the neuroprotective effects of OCN on PD, and the FFAR3, expressed in enteric nervous system, might be the main action site of propionate. Video abstract.

An inverted U-shaped relationship between parathyroid hormone and body weight, body mass index, body fat.

PURPOSE: To investigate the relationship between parathyroid hormone (PTH) levels and body weight, body mass index (BMI), lipid profiles, and fat distribution in subjects with primary hyperparathyroidism (PHPT) and controls. METHODS: This was a cross-sectional study in 192 patients with PHPT and 202 controls. Serum concentrations of calcium, 25-hydroxyvitamin D (25(OH)D), PTH, lipids profiles, and other hormones were quantified. Bone mineral density was assessed by dual-energy X-ray absorptiometry. Fat distribution evaluation utilizing quantitative computed tomography was conducted in another 66 patients with PHPT and 155 controls. RESULTS: PHPT patients were older (P < 0.001) and had less body weight (P < 0.001), lower BMI (P = 0.019), lower serum concentrations of 25(OH)D (P < 0.001), total cholesterol (P = 0.036), low-density lipoprotein-cholesterol (P = 0.036), and higher circulating concentration of free fatty acid (FFA) (P = 0.047) as compared with controls. After adjusting multiple confounders, PTH was positively correlated with weight (r = 0.311, P < 0.001), BMI (r = 0.268, P < 0.01), and visceral adipose tissue area (VAA) (r = 0.191, P < 0.05) in the first tertile of PTH. However, these associations were not observed in the second tertile. While in the third tertile, PTH was negatively correlated with weight (r = -0.200, P < 0.05), BMI (r = -0.223, P < 0.05) and marginally with VAA (r = -0.306, P = 0.065), it showed positive association with FFA (r = 0.230, P < 0.05). CONCLUSIONS: The inverted U-shape relationship between PTH and body weight, BMI, VAA found in this study is helpful to explain the conflicting results among these parameters, and extend our understanding of the metabolic effects of PTH.

LINC00473 contributes to the radioresistance of esophageal squamous cell carcinoma by regulating microRNA­497­5p and cell division cycle 25A.

Long non­coding RNA (lncRNA) LINC00473 plays a carcinogenic role in a variety of different tumor types. Nevertheless, the mechanisms through which LINC00473 regulates the radiosensitivity of esophageal squamous cell carcinoma (ESCC) cells remains elusive. In the present study, reverse transcription­quantitative PCR was used to quantify the expression of LINC00473, microRNA (miRNA/miR)­497­5p and cell division cycle 25A (CDC25A) in ESCC tissues. The association between LINC00473 expression and the clinicopathological characteristics of patients with ESCC was also assessed. Furthermore, Cell Counting kit­8 and colony formation assays were carried out to monitor the proliferation of ESCC cells exposed to X­ray radiation. A dual­luciferase reporter assay was also conducted to analyze the interaction between LINC00473 and miR­497­5p, as well as the interaction between CDC25A and miR­497­5p. The findings of the present study demonstrated that in ESCC tissues and cells, the expression levels of LINC00473 and CDC25A were significantly upregulated, while the expression of miR­497­5p was downregulated. The high expression level of LINC00473 was associated with a higher T stage, lymph node metastasis stage and a lower tumor differentiation grade in patients with ESCC. Following irradiation, transfection with miR­497­5p mimics reduced the promoting effect of LINC00473 overexpression on ESCC cell proliferation, and partially impeded the resistance of ESCC cells to X­ray radiation induced by LINC00473 overexpression. Moreover, transfection with miR­497­5p inhibitors partially alleviated the inhibitory effects of LINC00473 knockdown on cellular proliferation, and partly reversed the sensitivity of cells to X­ray irradiation induced by LINC00473 knockdown. Furthermore, it was confirmed that miR­497­5p was able to bind LINC00473 and the 3'­untranslated region of CDC25A. On the whole, the findings of the present study demonstrate that LINC00473 reduces the radiosensitivity of ESCC cells by modulating the miR­497­5p/CDC25A axis.

Endurance exercise protects aging Drosophila from high-salt diet (HSD)-induced climbing capacity decline and lifespan decrease by enhancing antioxidant capacity.

A high-salt diet (HSD) is a major cause of many chronic and age-related defects such as myocardial hypertrophy, locomotor impairment and mortality. Exercise training can efficiently prevent and treat many chronic and age-related diseases. However, it remains unclear whether endurance exercise can resist HSD-induced impairment of climbing capacity and longevity in aging individuals. In our study, flies were given exercise training and fed a HSD from 1-week old to 5-weeks old. Overexpression or knockdown of salt and dFOXO were built by UAS/Gal4 system. The results showed that a HSD, salt gene overexpression and dFOXO knockdown significantly reduced climbing endurance, climbing index, survival, dFOXO expression and SOD activity level, and increased malondialdehyde level in aging flies. Inversely, in a HSD aging flies, endurance exercise and dFOXO overexpression significantly increased their climbing ability, lifespan and antioxidant capacity, but they did not significantly change the salt gene expression. Overall, current results indicated that a HSD accelerated the age-related decline of climbing capacity and mortality via upregulating salt expression and inhibiting the dFOXO/SOD pathway. Increased dFOXO/SOD pathway activity played a key role in mediating endurance exercise resistance to the low salt tolerance-induced impairment of climbing capacity and longevity in aging DrosophilaThis article has an associated First Person interview with the first author of the paper.