The transcriptional control of LcIDL1-LcHSL2 complex by LcARF5 integrates auxin and ethylene signaling for litchi fruitlet abscission.

At the physiological level, the interplay between auxin and ethylene has long been recognized as crucial for the regulation of organ abscission in plants. However, the underlying molecular mechanisms remain unknown. Here, we identified transcription factors involved in indoleacetic acid (IAA) and ethylene (ET) signaling that directly regulate the expression of INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) and its receptor HAESA (HAE), which are key components initiating abscission. Specifically, litchi IDA-like 1 (LcIDL1) interacts with the receptor HAESA-like 2 (LcHSL2). Through in vitro and in vivo experiments, we determined that the auxin response factor LcARF5 directly binds and activates both LcIDL1 and LcHSL2. Furthermore, we found that the ETHYLENE INSENSITIVE 3-like transcription factor LcEIL3 directly binds and activates LcIDL1. The expression of IDA and HSL2 homologs was enhanced in LcARF5 and LcEIL3 transgenic Arabidopsis plants, but reduced in ein3 eil1 mutants. Consistently, the expressions of LcIDL1 and LcHSL2 were significantly decreased in LcARF5- and LcEIL3-silenced fruitlet abscission zones (FAZ), which correlated with a lower rate of fruitlet abscission. Depletion of auxin led to an increase in 1-aminocyclopropane-1-carboxylic acid (the precursor of ethylene) levels in the litchi FAZ, followed by abscission activation. Throughout this process, LcARF5 and LcEIL3 were induced in the FAZ. Collectively, our findings suggest that the molecular interactions between litchi AUXIN RESPONSE FACTOR 5 (LcARF5)-LcIDL1/LcHSL2 and LcEIL3-LcIDL1 signaling modules play a role in regulating fruitlet abscission in litchi and provide a long-sought mechanistic explanation for how the interplay between auxin and ethylene is translated into the molecular events that initiate abscission.

The L-shaped association of mid-upper arm circumference with all-cause and cause-specific mortality in US adults: a population-based prospective cohort study.

BACKGROUND: The arm circumference is a feasible and reliable indicator in evaluating the nutritional status of children. However, its application in general adults has yet to be thoroughly investigated. OBJECTIVE: This study aimed to evaluate the association between mid-upper arm circumferences (MUACs) and mortality in general adults. METHODS: The nationally representative cohort from the National Health and Nutrition Examination Survey (1999-2018) was analyzed with mortality information obtained through linkage to the National Death Index. The baseline MUACs were collected as exposure. Survey-weighted Cox proportional hazard regressions were performed to estimate the hazard ratios (HRs) and 95% confidential intervals (CIs) of mortality risk for individuals with different MUACs. Restricted cubic spline analyses were performed to examine the nonlinear association of MUAC with all-cause and cause-specific mortality. RESULTS: A total of 52,159 participants were included in this study. During a median follow-up time of 117 months, 7157 deaths were documented, with leading causes of cardiovascular disease (CVD), cancer, and respiratory disease. Individuals in the first quartile (Q1) of MUAC tended to have higher all-cause mortality risk than the rest after full adjustment. Similarly, CVD mortality risk in Q1 was higher than that in the second quartile (Q2) and the third quartile (Q3); respiratory mortality risk in Q1 was higher than in Q2. MUAC was non-linearly associated with all-cause mortality and CVD mortality. Individuals in Q1 MUAC (≤ 29.3) tended to have higher all-cause mortality risk, with HRs (95% CIs) estimated to be 0.76 (0.67-0.87) for Q2 (29.4, 32.5), 0.69 (0.59-0.81) for Q3 (32.6, 36.0), and 0.59 (0.46-0.75) for Q4 (≥ 36.1) after adjustment of demographic, lifestyle, and comorbidity covariates. Similarly, compared with Q1, HRs (95% CIs) for CVD mortality were estimated to be 0.73 (0.58-0.93) for Q2 and 0.57 (0.43-0.47) for Q3; HRs (95% CIs) for respiratory mortality was estimated to be 0.57 (95% CI, 0.37-0.87) for Q2 with other differences not significant. CONCLUSION: The MUAC was inversely associated with long-term mortality in general adults in the United States and may serve as a valuable measurement in adult health evaluations.

Chrysophanol postconditioning attenuated cerebral ischemia-reperfusion injury induced NLRP3-related pyroptosis in a TRAF6-dependent manner.

Individuals who suffer from post-CA (cardiac arrest) brain injury experience higher mortality and more severe functional disability. Neuroinflammation has been identified as a vital factor in cerebral ischemia-reperfusion injury (CIRI) following CA. Pyroptosis induces neuronal death by triggering an excessive inflammatory injury. Chrysophanol possesses robust anti-inflammatory features, and it is protective against CIRI. The purpose of this research was to assess the effect of Chrysophanol postconditioning on CIRI-induced pyroptotic cell death, and to explore its underlying mechanisms. CIRI was induced in rats by CA and subsequent cardiopulmonary resuscitation, and PC12 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to imitate CIRI in vitro. It was found that post-CA brain injury led to a notable cerebral damage revealed by histopathological changes and neurological outcomes. The existence of pyroptosis was also confirmed in in vivo and in vitro CIRI models. Moreover, we further confirmed that Chrysophanol, the main bioactive ingredient of Rhubarb, significantly suppressed expressions of pyroptosis-associated proteins, e.g., NLRP3, ASC, cleaved-caspase-1 and N-terminal GSDMD, and inhibited the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6). Furthermore, NLRP3 overexpression neutralized the neuroprotection of Chrysophanol postconditioning, suggesting that pyroptosis was the major neuronal death pathway modulated by Chrysophanol postconditioning in OGD/R. Additionally, the neuroprotection of Chrysophanol postconditioning was also abolished by gain-of-function analyses of TRAF6. Finally, the results demonstrated that Chrysophanol postconditioning suppressed the interaction between TRAF6 and NLRP3. Taken together, our findings revealed that Chrysophanol postconditioning was protective against CIRI by inhibiting NLRP3-related pyroptosis in a TRAF6-dependent manner.

Burden of brain and other central nervous system cancer in China, 1990-2019: a systematic analysis of observational data from the global burden of disease study 2019.

OBJECTIVE: To evaluate the trends in disease burden and the epidemiological features of central nervous system (CNS) cancer in China from 1990 to 2019. DESIGN: A population-based observational study. SETTING: The incidence, prevalence, death and disability-adjusted life years (DALYs) due to CNS cancer in China, stratified by sex, age and provincial region, were collected from the Global Burden of Disease Study 2019. PARTICIPANTS: Data were publicly available and individuals were not involved. RESULTS: In 2019, the incident cases of CNS cancer in China were 347 992 (95% UI 262 084-388 896), and the age-standardised rate (ASR) of incidence was 5.69 (95% UI 4.36-6.78) per 100 000 person-years increased by 27.9% compared with that in 1990; meanwhile, CNS cancer caused 63 527 (95% UI 47 793-76 948) deaths in China in 2019, and the ASR of death was 3.5 (95% UI 2.62-4.21) per 100 000 person-years decreased by 9.6%. The ASRs of incidence and prevalence of CNS cancer in China increased more rapidly than the global average; meanwhile, the ASRs of DALYs owing to CNS cancer declined more rapidly. The burden of CNS cancer showed no significant differences between men and women, but was more pronounced in early childhood and old adulthood. The ASRs of incidence and prevalence were higher in high-income provinces, confirmed by the positive correlation with Sociodemographic Index (SDI), with correlation coefficient r of 0.322 and 0.767, respectively (both p<0.0001). However, the ASRs of death and DALYs demonstrated a negative correlation with SDI, with r of -|0.319 and -0.642, respectively (both p<0.0001). CONCLUSIONS: From a global perspective, China has been bearing a substantial burden of CNS cancer. More attention should be paid to children and elderly populations for CNS cancer. The disease burden varied significantly at the subnational level of China, which was associated with socioeconomic development.

Prognostic Factors and Treatment Strategies for Elderly Patients with Malignant Meningioma: A SEER Population-Based Study.

Objective: Malignant meningioma (MM) is a relatively rare disease with poor survival. Few studies had focused on MM in the elderly population. This study aims to explore the prognostic factors and optimal therapeutic strategy in elderly patients with MM. Methods: We took advantage of the Surveillance, Epidemiology, and End Results (SEER) database to include 275 adult patients with histologically confirmed MM between 2011 and 2018. The Kaplan-Meier curves were plotted by different covariates to reveal the survival probability. Univariate and multivariable Cox proportional hazard regression analyses were applied to identify prognostic factors for cancer-specific survival (CSS). Results: The multivariable analysis in the elderly group revealed that when compared with patients receiving gross total resection (GTR), patients receiving biopsy had significantly worse CSS (HR = 3.72; 95% CI: 1.35-10.21; P = 0.011), whereas patients receiving subtotal resection (STR) had nearly the same CSS (HR = 0.83; 95% CI: 0.37-1.86; P = 0.653). Meanwhile, postoperative radiotherapy (PORT) showed no significant association with CSS in the elderly patient group (HR = 0.94; 95% CI: 0.42-2.12; P = 0.888). Conclusion: Surgical resection is recommended for elderly patients with MM in the absence of surgical contraindications, but GTR does not present survival benefit in the elderly patients compared with STR. Additional large-scale clinical studies are needed to explore the survival benefit of PORT applied in patients with MM.

L-shaped association of serum calcium with all-cause and CVD mortality in the US adults: A population-based prospective cohort study.

Background: Calcium is involved in many biological processes, but the impact of serum calcium levels on long-term mortality in general populations has been rarely investigated. Methods: This prospective cohort study analyzed data from the National Health and Nutrition Examination Survey (1999-2018). All-cause mortality, cardiovascular disease (CVD) mortality, and cancer mortality were obtained through linkage to the National Death Index. Survey-weighted multivariate Cox regression was performed to compute hazard ratios (HRs) and 95% confidential intervals (CIs) for the associations of calcium levels with risks of mortality. Restricted cubic spline analyses were performed to examine the non-linear association of calcium levels with all-cause and disease-specific mortality. Results: A total of 51,042 individuals were included in the current study. During an average of 9.7 years of follow-up, 7,592 all-cause deaths were identified, including 2,391 CVD deaths and 1,641 cancer deaths. Compared with participants in the first quartile (Q1) of serum calcium level [≤2.299 mmol/L], the risk of all-cause mortality was lower for participants in the second quartile (Q2) [2.300-2.349 mmol/L], the third quartile (Q3) [2.350-2.424 mmol/L] and the fourth quartile (Q4) [≥2.425 mmol/L] with multivariable-adjusted HRs of 0.81 (95% CI, 0.74-0.88), 0.78 (95% CI, 0.71-0.86), and 0.80 (95% CI, 0.73, 0.88). Similar associations were observed for CVD mortality, with HRs of 0.82 (95% CI, 0.71-0.95), 0.87 (95% CI, 0.74-1.02), and 0.83 (95% CI, 0.72, 0.97) in Q2-Q4 quartile. Furthermore, the L-shaped non-linear associations were detected for serum calcium with the risk of all-cause mortality. Below the median of 2.350 mmol/L, per 0.1 mmol/L higher serum calcium was associated with a 24% lower risk of all-cause mortality (HR: 0.76, 95% CI, 0.70-0.83), however, no significant changes were observed when serum calcium was above the median. Similar L-shaped associations were detected for serum calcium with the risk of CVD mortality with a 25% reduction in the risk of CVD death per 0.1 mmol/L higher serum calcium below the median (HR: 0.75, 95% CI, 0.65-0.86). Conclusion: L-shaped associations of serum calcium with all-cause and CVD mortality were observed in US adults, and hypocalcemia was associated with a higher risk of all-cause mortality and CVD mortality.

Competing risk model to determine the prognostic factors and treatment strategies for elderly patients with glioblastoma.

The prognostic factors and optimal treatment for the elderly patient with glioblastoma (GBM) were poorly understood. This study extracted 4975 elderly patients (≥ 65 years old) with histologically confirmed GBM from Surveillance, Epidemiology and End Results (SEER) database. Firstly, Cumulative incidence function and cox proportional model were utilized to illustrate the interference of non-GBM related mortality in our cohort. Then, the Fine-Gray competing risk model was applied to determine the prognostic factors for GBM related mortality. Age ≥ 75 years old, white race, size > 5.4 cm, frontal lobe tumor, and overlapping lesion were independently associated with more GBM related death, while Gross total resection (GTR) (HR 0.87, 95%CI 0.80-0.94, P = 0.010), radiotherapy (HR 0.64, 95%CI 0.55-0.74, P < 0.001), chemotherapy (HR 0.72, 95%CI 0.59-0.90, P = 0.003), and chemoRT (HR 0.43, 95%CI 0.38-0.48, P < 0.001) were identified as independently protective factors of GBM related death. Based on this, a corresponding nomogram was conducted to predict 3-, 6- and 12-month GBM related mortality, the C-index of which were 0.763, 0.718, and 0.694 respectively. The calibration curve showed that there was a good consistency between the predicted and the actual mortality probability. Concerning treatment options, GTR followed by chemoRT is suggested as optimal treatment. Radiotherapy and chemotherapy alone also provide moderate clinical benefits.

The Survival Benefits of Surgical Resection and Adjuvant Therapy for Patients With Brainstem Glioma.

PURPOSE: The role of surgical resection in the treatment of brainstem glioma (BSG) is poorly understood. For pediatric low-grade (LGBSG) group, several monocentric small-scale retrospective studies reported contradictory conclusions. And there was no clinical study focused on surgical resection for adult or pediatric high-grade (HG) patient groups. This study aims to illustrate whether surgical resection and adjuvant therapy provide survival benefits for patients with histologically confirmed BSG. PATIENTS AND METHODS: This retrospective cohort study included 529 patients with histologically confirmed BSG in Surveillance Epidemiology and End Results (SEER) database from 2006-2015. Patients were divided into four groups by age and World Health Organization (WHO) grade. Kaplan-Meier curves of CSS were plotted by different treatment options to compare the survival probability. Univariate and multivariable analyses were then conducted to determine the prognosis effects of surgical resection and adjuvant therapy on cancer specific survival (CSS). All analyses were done in four different groups separately. RESULTS: The final sample included 529 patients. The entire study population was divided into groups of pediatric LG (n=236, 44.6%), pediatric HG (n=37, 7.0%), adult LG (n=204, 38.6%) and adult HG (n=52, 9.8%). 52.7% (n=144) of pediatric patients had pilocytic astrocytoma and 45.3% (n=116) of adult patients had ependymoma. Pediatric LGBSG group had the highest gross total resection (GTR) rate (61.4%) and 5-year CSS rate (88.6%). Kaplan-Meier curves of pediatric LGBSG group revealed that patients treated with GTR had significantly better survival probability (P=0.033). Multivariable analysis identified GTR as independently significant predictor for prolonged CSS in pediatric LGBSG group (HR0.29, 95%CI 0.11-0.78, P=0.015); Surgical resection showed no relation to CSS in other patient groups. Kaplan-Meier curves of adult HGBSG group showed that patients treated with both RT and CT in adult HGBSG group had the best survival probability (P=0.02). However, multivariable analysis showed the combination of radiotherapy (RT) and chemotherapy (CT) was not significantly related to better CSS in adult HGBSG group (HR0.35, 95%CI 0.11-1.09, P=0.070). Adjuvant therapy didn't associate with better CSS in other patient groups. CONCLUSION: Pediatric LGBSG group had the highest GTR rate and the most favorable clinical outcome. GTR can provide significant survival benefits for pediatric LGBSG group.

The Epidemiological Characteristics and Prognostic Factors of Low-Grade Brainstem Glioma: A Real-World Study of Pediatric and Adult Patients.

Purpose: Our current understanding of low-grade brainstem glioma (LGBSG) is still limited. This study aimed to conduct a large-scale population-based real-world study to understand the epidemiological characteristics of LGBSG and determine the predictive factors of cancer-specific survival (CSS) and overall survival (OS) of LGBSG patients. Patients and Methods: We used Surveillance Epidemiology and End Results database to conduct this study of patients with histologically confirmed LGBSG. Patient demographics, tumor characteristics, and treatment options were compared between pediatric and adult patients. Univariate and multivariate analyses were employed to determine prognostic factors of CSS and OS. Kaplan-Meier curve and decision tree were used to confirm the prognostic factors. All variables were further identified by L1-penalized (Lasso) regression and then a nomogram was established to predict the 5- and 8-year CSS and OS rate. The precision of the nomogram was evaluated by calibration plots, Harrell's concordance index, and time-dependent receiver operating characteristic curve. The clinical use of nomogram was estimated by decision curve analysis. Results: A cohort of 305 patients with LGBSG, including 165 pediatric and 140 adult patients, was analyzed. Adult and pediatric patients showed different patterns concerning tumor size, tumor extension, adjuvant therapy, and survival rate. Univariate analysis revealed that pediatric group, gross total resection (GTR), World Health Organization grade II, radiotherapy, extension to ventricular system, and diffuse astrocytic and oligodendroglial tumor (DAOT) were significantly associated with CSS. Multivariate analysis showed that pediatric group, metastasis, ventricular system involvement, and DAOT were independently associated with CSS. The prognostic factors were further confirmed by Kaplan-Meier curve and decision tree. Kaplan-Meier curve also showed that adjuvant therapy added no benefits in patients with GTR and non-GTR. In addition, the nomogram was developed and the C-index of internal validation for CSS was 0.87 (95% CI, 0.78-0.96). Conclusion: This study shows that pediatric and adult patients have different tumor characteristics, treatment options, and survival rate. Pediatric group, DAOT, ventricular system involvement, and metastasis were identified as independent prognostic factors for CSS by multivariate analysis. Adjuvant therapy showed no benefits on CSS in patients with GTR and non-GTR. The nomogram was discriminative and clinically useful.

Prognostic value of long non-coding RNA SNHG20 in cancer: A meta-analysis.

BACKGROUND: Small nucleolar RNA host gene 20 (SNHG20) is a newly identified long non-coding RNA (lncRNA). Accumulative evidence suggest that SNHG20 is highly related to tumorigenesis. However, whether the levels of SNHG20 can be used for prognosis of patients with different cancer types was unclear. The present study aims to explore the role of SNHG20 in tumor prognosis and its clinical significance. METHODS: Related articles published before March 14, 2019 were searched in PubMed, Excerpta Medica Database (EMBASE), ISI Web of Science, and China National Knowledge Infrastructure (CNKI). Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were obtained using Stata 11.0 software and used to for determination of the link between the levels of SNHG20 and overall survival (OS). Fixed or random model was chosen depending on the heterogeneity of the studies. A quality assessment of the included studies was performed according to the Newcastle-Ottawa scale. This study was approved by the Medical Ethics Committee of Xiangya Hospital of Central South University. RESULTS: After a strict filtering process, a total of 1149 patients from 15 studies were enrolled in this study. Pooled data showed that elevated level of SNHG20 was correlated not only with poor overall survival (HR = 2.49, 95% confidence interval (CI): 2.05-2.98), but also with tumor-node-metastasis stage (TNM) (odds ratio (OR) = 3.32, 95% CI: 2.27-4.86), high histological grade (OR = 2.11, 95% CI: 1.55-2.87), tumor size (OR = 2.92, 95% CI: 2.17-3.91), and lymph node metastasis (OR = 4.48, 95% CI: 2.90-6.92). Of note, there is no significant heterogeneity difference among the studies. CONCLUSION: Up-regulated SNHG20 predicts unfavorable prognosis for multiple kinds of cancers although further studies are in need to verify its clinical applications.