Inositol hexakisphosphate (IP₆) provides a phosphorous reservoir in plant seeds; in addition, along with its biosynthesis intermediates and derivatives, IP₆ also plays important roles in diverse ...developmental and physiological processes. Disruption of the Arabidopsis inositol pentakisphosphate 2‐kinase coding gene AtIPK1 was previously shown to reduce IP₆ content in vegetative tissues and affect phosphate (Pi) sensing. Here we show that AtIPK1 is required for sustaining plant growth, as null mutants are non‐viable. An incomplete loss‐of‐function mutant, atipk1‐1, exhibited disturbed Pi homeostasis and overaccumulated Pi as a consequence of increased Pi uptake activity and root‐to‐shoot Pi translocation. The atipk1‐1 mutants also showed a Pi deficiency‐like root system architecture with reduced primary root and enhanced lateral root growth. Transcriptome analysis indicated that a subset of Pi starvation‐responsive genes was transcriptionally perturbed in the atipk1‐1 mutants and the expression of multiple genes involved in Pi uptake, allocation, and remobilization was increased. Genetic and transcriptional analyses suggest that disturbance of Pi homeostasis caused by atipk1 mutation involved components in addition to PHR1(‐like) transcription factors. Notably, the transcriptional increase of a number of Pi starvation‐responsive genes in the atipk1‐1 mutants is correlated with the reduction of histone variant H2A.Z occupation in chromatin. The myo‐inositol‐1‐phosphate synthase mutants, atmips1 and atmips2 with comparable reduction in vegetative IP₆ to that in the atipk1‐1 mutants did not overaccumulate Pi, suggesting that Pi homeostasis modulated by AtIPK1 is not solely attributable to IP₆ level. This study reveals that AtIPK1 has important roles in growth and Pi homeostasis.
Plant vacuoles serve as the primary intracellular compartments for inorganic phosphate (Pi) storage. Passage of Pi across vacuolar membranes plays a critical role in buffering the cytoplasmic Pi ...level against fluctuations of external Pi and metabolic activities. Here we demonstrate that the SPX-MFS proteins, designated as PHOSPHATE TRANSPORTER 5 family (PHT5), also named Vacuolar Phosphate Transporter (VPT), function as vacuolar Pi transporters. Based on (31)P-magnetic resonance spectroscopy analysis, Arabidopsis pht5;1 loss-of-function mutants accumulate less Pi and exhibit a lower vacuolar-to-cytoplasmic Pi ratio than controls. Conversely, overexpression of PHT5 leads to massive Pi sequestration into vacuoles and altered regulation of Pi starvation-responsive genes. Furthermore, we show that heterologous expression of the rice homologue OsSPX-MFS1 mediates Pi influx to yeast vacuoles. Our findings show that a group of Pi transporters in vacuolar membranes regulate cytoplasmic Pi homeostasis and are required for fitness and plant growth.
Skp2 is overexpressed in multiple cancers and plays a critical role in tumor development through ubiquitin/proteasome‐dependent degradation of its substrate proteins. Drugs targeting Skp2 have ...exhibited promising anticancer activity. Here, we identified a plant‐derived Skp2 inhibitor, betulinic acid (BA), via high‐throughput structure‐based virtual screening of a phytochemical library. BA significantly inhibited the proliferation and migration of non–small cell lung cancer (NSCLC) through targeting Skp2‐SCF E3 ligase both in vitro and in vivo. Mechanistically, BA binding to Skp2, especially forming H‐bonds with residue Lys145, decreases its stability by disrupting Skp1‐Skp2 interactions, thereby inhibiting the Skp2‐SCF E3 ligase and promoting the accumulation of its substrates; that is, E‐cadherin and p27. In both subcutaneous and orthotopic xenografts, BA significantly inhibited the proliferation and metastasis of NSCLC through targeting Skp2‐SCF E3 ligase and upregulating p27 and E‐cadherin protein levels. Taken together, BA can be considered a valuable therapeutic candidate to inhibit metastasis of NSCLC.
By screening a phytochemical library via high‐throughput molecular docking, we identified that betulinic acid is capable of binding to Skp2 at residue Lys145, leading to decreased protein stability of Skp2 and the accumulation of its substrate protein p27 and E‐cadherin. Betulinic acid significantly inhibited the proliferation and migration of NSCLC through downregulating Skp2 both in vitro and in vivo.
Epidemiological literature regarding the effect of polycystic ovary syndrome (PCOS) as a risk factor for non-alcoholic fatty liver disease (NAFLD) remains inconsistent. Furthermore, it remains ...debatable whether NAFLD is associated with PCOS as a consequence of shared risk factors or whether PCOS contributes to NAFLD in an independent fashion. Therefore, this meta-analysis was conducted.
This meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Relevant studies published before May 2017 were identified and retrieved from PubMed and Web of Science databases. The data were extracted, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.
A total of 17 studies were included into the present analysis. Compared to the control group, the risk of NAFLD in the PCOS group was higher (OR = 2.25, 95% CI = 1.95-2.60). When stratified by BMI and geographic location, the results indicated that the frequency of NAFLD risk was significantly higher in obese subjects (OR = 3.01, 95% CI = 1.88-4.82), non-obese subjects (OR = 2.07, 95% CI = 1.12-3.85), subjects from Europe (OR = 2.00, 95% CI = 1.58-2.52), subjects from the Asia-Pacific Region, (OR = 2.32, 95% CI = 1.89-2.84) and subjects from America (OR = 2.96, 95% CI = 1.93-4.55). In addition, PCOS patients with hyperandrogenism (HA) had a significantly higher risk of NAFLD, compared with controls (OR = 3.31, 95% CI = 2.58-4.24). However, there was no association between PCOS patients without HA and higher risk of NAFLD (OR = 1.46; 95% CI =0.55-3.87). The results of this meta-analysis should be interpreted with caution due to the small number of observational studies and possible confounding factors.
The meta-analysis results suggest that PCOS is significantly associated with high risk of NAFLD. Although this association was independent of obesity and geographic region, it might be correlated with HA.
•Landscape patterns effectively estimate major ion exports with 200 m riparian buffer width.•Landscape-level configuration metrics (PD, CONTAG, and IJI) account for most of the variations in cation ...discharges.•Class-level configuration metrics (EDBUD, PDBAR, and IJIAGR) primarily explain the variations in anion discharges.•No significant disparities in regression model performance are observed between wet and dry seasons.
The impacts of landscape pattern on water quality of streams are intricate and influenced by spatiotemporal scales. Untangling the interactions between landscapes and water, and identifying the pivotal indicators that drive spatial and temporal changes in nutrient dynamics, are essential steps towards facilitating sustainable water resource management. This study explored the relationship between landscape patterns and annual and seasonal (wet and dry seasons) exports of major cations (Na+, K+, Ca2+, and Mg2+) and anions (Cl-, SO42-, NO3-N, and PO4-P) in 43 watersheds across subtropical mountainous regions of Taiwan during the 2015–2016 period. Multiple stepwise regression models were constructed to elucidate the crucial landscape variables influencing variations in stream ion exports across different time scales, and spatial extent, ranging from watershed to various riparian buffer widths (100, 200, 500, 1000, 1500, and 2000 m). The findings indicated that the buffer width of 200 m emerged as the optimal scale for illustrating the connections between landscape patterns and water chemistry, outperforming larger scales. Nevertheless, there were minor deviations in the optimal scale for Na+ and Cl- (ranging from 100 to 500 m). Landscape-level configuration metrics (PD patch density, CONTAG Contagion, and IJI Interspersion and Juxtaposition) played a significant role in explaining the majority of data variations in cations. This suggest that overall landscape fragmentation tends to enhance cations exports, regardless of land cover types. On the contrary, class-level configuration metrics (EDBUD edge density of buildup, PDBAR patch density of bareland, and IJIAGR Interspersion and Juxtaposition of agriculture) played a primary role in interpreting data variations of anions. This indicated that the configurations of specific land cover types, such as buildup, agriculture and bareland, are the primary factors influencing anion exports. Furthermore, the regression models exhibited robust performance during both wet and dry seasons, implying their consistent efficacy in estimating ion exports. This synthesis illustrated the benefits of utilizing this cost-effective approach to assess landscape-water connections in challenging mountainous regions, assisting water resources management.
Three waves of hematopoiesis occur in the mouse embryo. The primitive hematopoiesis appears as blood islands in the extra embryonic yolk sac at E7.5. The extra embryonic pro-definitive hematopoiesis ...launches in late E8 and the embryonic definitive one turns on at E10.5 indicated by the emergence of hemogenic endothelial cells on the inner wall of the extra embryonic arteries and the embryonic aorta. To study the roles of SCL protein isoforms in murine hematopoiesis, the SCL-large (SCL-L) isoform was selectively destroyed with the remaining SCL-small (SCL-S) isoform intact. It was demonstrated that SCL-S was specifically expressed in the hemogenic endothelial cells (HECs) and SCL-L was only detected in the dispersed cells after budding from HECs. The
homozygous mutant embryos only survived to E10.5 with normal extra embryonic vessels and red blood cells. In wild-type mouse embryos, a layer of neatly aligned CD34
and CD43
cells appeared on the endothelial wall of the aorta of the E10.5 fetus. However, the cells at the same site expressed CD31 rather than CD34 and/or CD43 in the E10.5
embryo, indicating that only the endothelial lineage was developed. These results reveal that the SCL-S is sufficient to sustain the primitive hematopoiesis and SCL-L is necessary to launch the definitive hematopoiesis.
Although leisure-time physical activity (PA) has established health benefits in older adults, it is equivocal if exercising in environments with high levels of PM2.5 concentrations is equally ...beneficial for them. To explore the independent and joint associations of ambient PM2.5 and PA with all-cause mortality among adults aged 60 or older and to assess the modifying effect of age (60–74 years vs. 75+ years) on the joint associations.
A prospective cohort study based on the MJ Cohort repeat examinations (2005–2016) and the Taiwan Air Quality Monitoring Network and death registry linkages (2005–2022). We included MJ Cohort participants aged 60 or more at baseline who attended the health check-ups at least twice (n = 21,760). Metabolic equivalent hours per week (MET-h/week) of leisure-time PA were computed. Multivariable adjusted associations were examined using time-varying Cox proportional hazard models.
There were 3539 all-cause deaths over a mean follow-up of 12.81 (SD = 3.67) years. Ambient PM2.5 and physical inactivity are both independently associated with all-cause mortality. The joint associations of PA and PM2.5 concentrations with all-cause mortality differed in the young-old (60–74 years) and the older-old (75+ years) (P for interaction = 0.01); Higher levels of long-term PM2.5 exposures (≥25 μg/m3) had little influence on the associations between PA and mortality in the young-old (HR = 0.68 (0.56–0.83) and HR = 0.72 (0.59–0.88) for participants with 7.5–<15 and 15+ MET-h/week respectively) but eliminated associations between exposure and outcome in the older-old (HR = 0.91 (0.69–01.21) and HR = 1.02 (0.76–1.38) for participants with 7.5–<15 and 15+ MET-h/week).
Long-term exposures to higher PM2.5 concentrations may eliminate the beneficial associations of PA with all-cause mortality among adults aged 75 and over.
•Engaging in more physical activity (PA) and having a lower level of PM2.5 had a decreased mortality.•The joint association of PA and PM2.5 with mortality differed between young and older-old.•The benefit of PA for mortality was attenuated in adults (75+) with PM2.5 exposures (≥25 μg/m3).
Background: The prevalence of overweight is increasing dramatically worldwide. The aim of our study was to investigate the association of plain water intake (PWI) with the risk of new-onset ...overweight risk among Chinese adults. Methods: A total of 3,200 adults aged 18–65 who were free of overweight at baseline were enrolled from China Health and Nutrition Survey (CHNS) cohort study in 2006–2011. The risk of new-onset overweight with different amounts of PWI per day was analyzed in this 5-year cohort. A multiple logistic regression model was used to assess the association of PWI and the risk of new-onset overweight and adjust for potential confounders. Moreover, dose-response models were developed to estimate the linear relationship. Results: During 5 years of follow-up, 1,018 incident cases were identified. Our analysis indicated an inverse association of more than 4 cups of PWI per day and the risk of new-onset overweight among normal weight individuals. Compared with participants who drank 2 to 3 cups PWI, the adjusted odds ratios (OR) of overweight were 0.741 (95% confidence interval CI, 0.599–0.916) in participants who drank 4 to 5 cups PWI, and 0.547 (95% CI, 0.435–0.687) in participants who drank more than 6 cups PWI. The dose-response analysis showed that every cup of PWI was associated with a 6.5% and 8.4% decrease in the risk of new-onset overweight among men and women, respectively. The interactions of PWI and covariates on the risk of overweight were not found. Conclusion: Drinking more than 4 cups (≈1 liter) per day of plain water is associated with decrease in the risk of new-onset overweight among normal-weight individuals.
Background and Aim
Pancreatic elastase‐1 (PE‐1) has been investigated in pancreatic disorders. However, the reference interval (RI) of PE‐1 in blood remains unconfirmed. We aimed to establish the ...blood RI of PE‐1 in an adult population.
Methods
In this prospective cross‐sectional study, we enrolled 400 adults who had received the whole‐body physical check‐up program between May 1, 2019 and November 20, 2019. The serum and plasma PE‐1 levels were measured by latex turbidimetric immunoassay in different storage conditions (fresh, refrigerated, and frozen). The 95% and 99% RI of PE‐1 were calculated according to the Clinical & Laboratory Standards Institute guidelines. The correlations between PE‐1 and other parameters were analyzed using multivariable regression models. Ultimately, 38 patients with acute pancreatitis were prospectively recruited as the validation cohort.
Results
The PE‐1 levels in fresh serum were highly correlated with those in refrigerated (R2 = 0.998) or frozen (R2 = 0.942) samples; however, plasma should not be suggested in frozen conditions (plasma vs serum: R2 = 0.185). In the RI study population (202 male & 198 female participants), the median age was 52.6 (25–75% interquartile range: 43.1–61.0). The 95% and 99% RIs of PE‐1 were 30.0–221.0 and 22.0–359.0 ng/dL, respectively. Triglycerides (β = 0.106, P = 0.033), lipase (β = 0.154, P = 0.007), and CA19–9 (β = 0.130, P = 0.008) were independent factors associated with PE‐1. In the pancreatitis validation cohort, with a cut‐off value of 359.0 ng/dL, the sensitivity and specificity were 100% and 99.8%, respectively.
Conclusion
The RI of PE‐1 established in this study can be used for further applications. Serum is the suggested form for frozen sample storage.
The aim of this study was to assess the effect of preoperative sleep quality on acute postoperative pain in breast cancer patients.The Pittsburgh Sleep Quality Index questionnaire (PSQI) was used to ...assess the overall sleep status of women scheduled for unilateral modified radical mastectomy in the past month. Based on the responses, patients were allocated to good sleep group or poor sleep group. Postoperatively, acute pain was assessed using the numerical rating score in the first 24 hours; in addition, the requirement of analgesics and the incidence of postoperative complications were recorded.A total of 108 breast surgery patients were enrolled. Based on the PSQI results, 55 (51%) patients were allocated to poor sleep group and 53 (49%) to good sleep group. Pain scores were similar in the 2 groups at the end of surgery (P = .589); however, poor sleep group reported higher postoperative pain scores than the good sleep group at 2 (P = .002), 6 (P < .001), 12 (P < .001), and 24 (P = .002) hours after surgery. The incidence of severe pain in the poor sleep group was higher than that in the good sleep group (27% vs 8%, P = .018), and the ratio of participants who required rescued analgesics was greater in the poor sleep group (52% vs 22%, P = .002). In addition, patients with poor sleep quality had more postoperative complications and longer hospital stay.In this study, breast cancer patients with poor preoperative sleep quality reported more severe postoperative pain, required more analgesics, experienced more complications, and had longer hospital stay.
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