Association Between Changes in Preoperative Serum Creatinine and Acute Kidney Injury After Cardiac Surgery: A Retrospective Cohort Study.

INTRODUCTION: Limited information exists regarding the impact of preoperative serum creatinine changes on cardiac surgery-associated acute kidney injury (CSA-AKI). This study aimed to investigate the development of AKI in patients with a baseline estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 who present with an elevation in preoperative serum creatinine. METHODS: This retrospective cohort study assessed patients who underwent open-heart surgery. Preoperative serum creatinine change was calculated as the ratio of the maximum preoperative serum creatinine value to the baseline creatinine (MCR). Patients were categorized into three groups based on MCR: non-elevation (≤1.0), mild elevation (1.0 to 1.5), and pronounced elevation (≥1.5). Multivariable logistic regression was used to estimate the risk of AKI, severe AKI, and non-recovery from AKI. RESULTS: There were significant increases in the odds of AKI (adjusted odds ratio [OR], 1.42; 95% confidence interval [CI], 1.29-1.57; per 0.1 increase in MCR), severe AKI (adjusted OR, 1.28; 95% CI, 1.15-1.41), and AKI non-recovery (adjusted OR, 1.29; 95% CI, 1.16-1.43). Pronounced elevation in preoperative serum creatinine was associated with a higher risk of AKI (adjusted OR, 15.45; 95% CI, 6.63-36.00), severe AKI (adjusted OR, 3.62; 95% CI, 1.20-10.87), and AKI non-recovery (adjusted OR, 4.74; 95% CI, 1.63-13.89) than non-elevation. Mild elevation in preoperative serum creatinine was also significantly associated with AKI (adjusted OR, 3.76; 95% CI, 1.92-7.37). CONCLUSIONS: Elevation in preoperative serum creatinine from baseline was associated with an increased risk of AKI; even mild elevation significantly increased the risk of AKI.

Interparental Conflict and Early Adolescent Depressive Symptoms: Parent-Child Triangulation as the Mediator and Grandparent Support as the Moderator.

A notable ambiguity persists concerning whether distinct forms of parent-child triangulation (unstable coercive coalition, stable coalition, detouring-attacking, detouring supportive, parentification) might mediate the association between interparental conflict and early adolescent depressive symptoms similarly within the context of Chinese Confucianism. Filling this research gap, this study aimed to examine the mediating role of the five dimensions of parent-child triangulation in the association between interparental conflict and early adolescent depressive symptoms, as well as the moderating effect of grandparent support on this mediating pathway. Data were drawn from a sample of 761 Chinese adolescents (M age = 12.82 ± 0.47, 49.1% girls). Structural equation model analyses indicated that unstable coercive coalition, stable coalition, and detouring-attacking behaviors partially mediated the association between interparental conflict and adolescent depressive symptoms, while detouring-supportive behaviors and parentification did not demonstrate such mediating effects. Unlike Western societies, a negative correlation was observed between interparental conflict and parentification in the context of China. Grandparent support mitigated the adverse effects of both interparental conflict and the unstable coercive coalition on early adolescent depressive symptoms.

Cumulative Genetic Scores Interact with Maternal and Paternal Parenting in Predicting Parent-Adolescent Cohesion and Conflict.

Previous research concerning the interplay between genetics and parenting in the development of the parent-child relationship during adolescence has been extremely scarce, predominantly adopting single-gene designs. This limited body of work has largely overlooked the distinct effects of maternal and paternal roles, as well as potential gender differences. Additionally, existing gene-by-environment (G × E) studies have mainly concentrated on adverse environmental factors and associated negative outcomes, somewhat neglecting positive environments and outcomes. The present study examined the interactions of cumulative genetic scores (CGS, dopamine receptor D2 TaqIA and oxytocin receptor gene rs53576 polymorphisms) with both positive and negative parenting on parent-adolescent cohesion and conflict. Furthermore, this study aimed to ascertain with which gene-environment model the potential G × E interactions would align. A total of 745 Chinese Han adolescents (Mage = 13.36 ± 0.96 years; 46.8% girls) from grades 7 to 9 participated in this study. Results revealed a significant effect of CGS and negative maternal parenting on mother-adolescent conflict among males, consistent with the weak differential susceptibility model. As CGS increased, the effects of negative maternal parenting on mother-son conflict were magnified. These findings have implications for the timing and focus of interventions aimed at improving parent-adolescent relationships.

Prognostic value of pretreatment diffusion-weighted imaging score for acute basilar artery occlusion with successful endovascular recanalization.

PURPOSE: The aim of this study is to test the prognostic value of a diffusion-weighted imaging (DWI) score in acute basilar artery occlusion (ABAO) with successful recanalization. METHODS: The DWI-based pons-midbrain and thalamus (PMT) score was developed to assess posterior circulation infarcts. We test its prognostic value and compare it with other two established scales, the DWI-based posterior circulation acute stroke prognosis Early CT score (PC-ASPECTS) and brain stem score (BSS). A retrospective cohort of consecutive ABAO patients with pretreatment magnetic resonance imaging and successful recanalization (defined as modified Thrombolysis in Cerebral Infarction 2b-3) were analyzed. A favorable outcome was defined as a 90-day modified Rankin Scale (mRS) score of 2 or less. The prognostic performance of three scales was estimated by receiver operating characteristic (ROC) curve analyses. RESULTS: One hundred and sixteen eligible patients (mean age, 59.1 ± 11.7 [standard deviation]; 96 [82.8%] man) were included and evaluated. Between favorable (mRS ≤ 2) and unfavorable groups, the baseline PMT score (median [interquartile range], 3 [1-4] versus 6 [5-8]; P < 0.001) differs significantly. ROC curve analyses showed the PMT score had the best prognostic value for favorable outcome (area under the curve, PMT versus BSS versus PC-ASPECTS = 0.80 versus 0.72 versus 0.68, P = 0.010). Multivariate logistic regression analyses showed baseline National Institute of Health stroke scale (OR, 0.90 [95%CI, 0.86-0.95], P = 0.004) and PMT score < 5 (OR, 17.83 [95%CI, 3.91-81.19], P < 0.001) were independent prognostic factors of favorable outcome. CONCLUSIONS: The PMT score seems to predict clinical outcome of ABAO patients with successful recanalization.

Association Between Glycemic Gap and Mortality in Critically Ill Patients with Diabetes.

OBJECTIVES: Dysglycemia is associated with poor outcomes in critically ill patients,which is uncertain in patients with diabetes regarding to the situation of glucose control before hospitalization. This study was aimed to investigate the effect of the difference between the level of blood glucose during ICU stay and before admission to ICU upon the outcomes of critically ill patients with diabetes. METHOD: Patients with diabetes expected to stay for more than 24hs were enrolled, HbA1c was converted to A1C-derived average glucose (ADAG) by the equation: ADAG = [ (HbA1c * 28.7) - 46.7 ] * 18-1, blood glucose were measured four times a day during the first 7 days after admission, the mean glucose level(MGL) and SOFA (within 3, 5, and 7days) were calculated for each person, GAPadm and GAPmean was calculated as admission blood glucose and MGL minus ADAG, the incidence of moderate hypoglycemia(MH), severe hypoglycemia (SH), total dosage of glucocorticoids and average daily dosage of insulin, duration of renal replacement therapy(RRT), ventilator-free hours, and non-ICU days were also collected. Patients were divided into survival group and nonsurvival group according to survival or not at 28-day, the relationship between GAP and mortality were analyzed. RESULTS: 431 patients were divided into survival group and nonsurvival group. The two groups had a comparable level of HbA1c, the nonsurvivors had greater APACHE II, SOFA, GAPadm, GAPmean-3, GAPmean-5, GAPmean-7 and higher MH and SH incidences. Less duration of ventilator-free, non-ICU stay and longer duration of RRT were recorded in the nonsurvival group. GAPmean-5 had the greatest predictive power with an AUC of 0.807(95%CI: 0.762-0.851), the cut-off value was 3.6 mmol/L (sensitivity 77.7% and specificity 76.6%). The AUC was increased to 0.852(95%CI: 0.814-0.889) incorporated with SOFA5 (NRI = 11.34%). CONCLUSION: Glycemic GAP between the MGL within 5 days and ADAG was independently associated with 28-day mortality of critically ill patients with diabetes. The predictive power was optimized with addition of SOFA5.

Sulfur dioxide improves the thermotolerance of maize seedlings by regulating salicylic acid biosynthesis.

Heat stress (HS) has become a serious threat to crop growth and yield. Sulfur dioxide (SO2) is being verified as a signal molecule in regulating the plant stress response. However, it is unknown whether SO2 plays a significant role in the plant heat stress response (HSR). Herein, maize seedlings were pretreated with various concentrations of SO2 and then kept at 45 °C for heat stress treatment, aiming to study the effect of SO2 pretreatment on HSR in maize by phenotypic, physiological, and biochemical analyses. It was found that SO2 pretreatment greatly improved the thermotolerance of maize seedlings. The SO2-pretreated seedlings showed 30-40% lower ROS accumulation and membrane peroxidation, but 55-110% higher activities of antioxidant enzymes than the distilled water-pretreated seedlings under heat stress. Interestingly, endogenous salicylic acid (SA) levels were increased by ∼85% in SO2-pretreated seedlings, as revealed by phytohormone analyses. Furthermore, the SA biosynthesis inhibitor paclobutrazol markedly reduced SA levels and attenuated SO2-triggered thermotolerance of maize seedlings. Meanwhile, transcripts of several SA biosynthesis and signaling, and heat stress-responsive genes in SO2-pretreated seedlings were significantly elevated under HS. These data have demonstrated that SO2 pretreatment increased endogenous SA levels, which activated the antioxidant machinery and strengthened the stress defense system, thereby improving the thermotolerance of maize seedlings under HS. Our current study provides a new strategy for mitigating heat stress damage for safe crop production.

The attributable mortality of sepsis for acute kidney injury: a propensity-matched analysis based on multicenter prospective cohort study.

BACKGROUND: Both sepsis and AKI are diseases of major concern in intensive care unit (ICU). This study aimed to evaluate the excess mortality attributable to sepsis for acute kidney injury (AKI). METHODS: A propensity score-matched analysis on a multicenter prospective cohort study in 18 Chinese ICUs was performed. Propensity score was sequentially conducted to match AKI patients with and without sepsis on day 1, day 2, and day 3-5. The primary outcome was hospital death of AKI patients. RESULTS: A total of 2008 AKI patients (40.9%) were eligible for the study. Of the 1010 AKI patients with sepsis, 619 (61.3%) were matched to 619 AKI patients in whom sepsis did not develop during the screening period of the study. The hospital mortality rate of matched AKI patients with sepsis was 205 of 619 (33.1%) compared with 150 of 619 (24.0%) for their matched AKI controls without sepsis (p = 0.001). The attributable mortality of total sepsis for AKI patients was 9.1% (95% CI: 4.8-13.3%). Of the matched patients with sepsis, 328 (53.0%) diagnosed septic shock. The attributable mortality of septic shock for AKI was 16.2% (95% CI: 11.3-20.8%, p < 0.001). Further, the attributable mortality of sepsis for AKI was 1.4% (95% CI: 4.1-5.9%, p = 0.825). CONCLUSIONS: The attributable hospital mortality of total sepsis for AKI were 9.1%. Septic shock contributes to major excess mortality rate for AKI than sepsis. REGISTRATION FOR THE MULTICENTER PROSPECTIVE COHORT STUDY: registration number ChiCTR-ECH-13003934.

The effects of timing onset and progression of AKI on the clinical outcomes in AKI patients with sepsis: a prospective multicenter cohort study.

BACKGROUND: Limited studies are available concerning on the earlier identification of AKI with sepsis. The aim of the study was to identify the risk factors of AKI early which depended on the timing onset and progression of AKI and investigate the effects of timing onset and progression of AKI on clinical outcomes. METHODS: Patients who developed sepsis during their first 48-h admission to ICU were included. The primary outcome was major adverse kidney events (MAKE) consisted of all-cause mortality, RRT-dependence, or an inability to recover to 1.5 times of the baseline creatinine value up to 30 days. We determined MAKE and in-hospital mortality by multivariable logistic regression and explored the risk factors of early persistent-AKI. C statistics were used to evaluate model fit. RESULTS: 58.7% sepsis patients developed AKI. According to the timing onset and progression of AKI, Early transient-AKI, early persistent-AKI, late transient-AKI, late persistent-AKI were identified. Clinical outcomes were quite different among subgroups. Early persistent-AKI had 3.0-fold (OR 3.04, 95% CI 1.61 - 4.62) risk of MAKE and 2.6-fold (OR 2.60, 95%CI 1.72 - 3.76) risk of in-hospital mortality increased compared with the late transients-AKI. Older age, underweight, obese, faster heart rate, lower MAP, platelet, hematocrit, pH and energy intake during the first 24 h on ICU admission could well predict the early persistent-AKI in patients with sepsis. CONCLUSION: Four AKI subphenotypes were identified based on the timing onset and progression of AKI. Early persistent-AKI showed higher risk of major adverse kidney events and in-hospital mortality. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trials Registry (www.chictr.org/cn) under registration number ChiCTR-ECH-13003934.

Low density lipoprotein cholesterol is associated with increased risk of cardiovascular disease in participants over 70 years old: A prospective cohort study.

BACKGROUND AND AIMS: Previous studies have indicated that the association of elevated low-density lipoprotein cholesterol (LDL-C) with cardiovascular disease (CVD) varies greatly with age, with the association being much stronger in younger than older individuals. To estimate the relationship between LDL-C and CVD risk in a contemporary population aged over 70 years in China. METHODS AND RESULTS: In this analysis, participants of China Health and Retirement Longitudinal Study (CHARLS) who did not take statins and did not have heart disease and stroke in 2011 were include and were followed up to 2018. The outcome of this analysis was the occurrence of CVD. Cox regression was used to assess the effect of LDL-C on CVD. We calculated E-values to quantify the effect of unmeasured confounding. In the 9,631 participants, 15.2% (N = 1,463) were aged over 70 years. During follow-up of 7 years, 1,437 participants had a first CVD attack. The Risk of CVD increased with each 10 mg/mL elevation in LDL-C in whole participants and all age groups. We noted a U-shaped relationship between LDL-C and risk of CVD in group over 70 years old, however, we further found that in the left side of U-shape curve, LDL-C was not associated with CVD, which indicated that a lower level of LDL-C could not increase the risk of CVD. E-value analysis suggested robustness to unmeasured confounding. CONCLUSIONS: In a contemporary society of China, elevated the level of LDL-C also increased the risk of CVD in participants over 70 years old. These results should strengthen guideline recommendations for the use of lipid-lowering therapies in those elderly.

Prognostic significance of malnutrition risk in elderly patients with acute kidney injury in the intensive care unit.

BACKGROUND: Malnutrition is common in critically ill patients, but nutrition status in critically ill patients with acute kidney injury (AKI) has been poorly studied. Our study aimed to investigate the relationship between malnutrition risk and the occurrence and prognosis of AKI in elderly patients in the intensive care unit (ICU). METHODS: Data were extracted from the Beijing Acute Kidney Injury Trial (BAKIT). A total of 1873 elderly patients were included and compared according to the clinical characteristics of AKI and non-AKI groups, and those of survivors and non-survivors of AKI in this study. Receiver operating characteristic (ROC) curves were used to analyse the predictive value of the modified Nutrition Risk in Critically Ill (mNUTRIC) score for the occurrence and 28-day prognosis of AKI. Multivariate Cox regression analysis was used to evaluate the effect of the mNUTRIC score on the 28-day mortality in AKI patients. RESULTS: Compared with the non-AKI group, AKI patients had higher mNUTRIC scores, and non-survivors had higher mNUTRIC scores than survivors in AKI population. Moreover, multivariate Cox regression showed that 28-day mortality in AKI patients increased by 9.8% (95% CI, 1.018-1.184) for every point increase in the mNUTRIC score, and the mNUTRIC score had good predictive ability for the occurrence of AKI and 28-day mortality in AKI patients. The mortality of AKI patients with mNUTRIC > 4 was significantly increased. CONCLUSIONS: The elderly patients are at high risk of malnutrition, which affects the occurrence and prognosis of AKI. Adequate attention should be given to the nutritional status of elderly patients. TRIAL REGISTRATION: This study was registered at www.chictr.org.cn (registration number Chi CTR-ONC-11001875) on 14 December 2011.

The predictive value of the Oxford Acute Severity of Illness Score for clinical outcomes in patients with acute kidney injury.

OBJECTIVE: To compare the performance of the Oxford Acute Severity of Illness Score (OASIS), the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, the Simplified Acute Physiology Score II (SAPS II), and the Sequential Organ Failure Assessment (SOFA) score in predicting 28-day mortality in acute kidney injury (AKI) patients. METHODS: Data were extracted from the Beijing Acute Kidney Injury Trial (BAKIT). A total of 2954 patients with complete clinical data were included in this study. Receiver operating characteristic (ROC) curves were used to analyze and evaluate the predictive effects of the four scoring systems on the 28-day mortality risk of AKI patients and each subgroup. The best cutoff value was identified by the highest combined sensitivity and specificity using Youden's index. RESULTS: Among the four scoring systems, the area under the curve (AUC) of OASIS was the highest. The comparison of AUC values of different scoring systems showed that there were no significant differences among OASIS, APACHE II, and SAPS II, which were better than SOFA. Moreover, logistic analysis revealed that OASIS was an independent risk factor for 28-day mortality in AKI patients. OASIS also had good predictive ability for the 28-day mortality of each subgroup of AKI patients. CONCLUSION: OASIS, APACHE II, and SAPS II all presented good discrimination and calibration in predicting the 28-day mortality risk of AKI patients. OASIS, APACHE II, and SAPS II had better predictive accuracy than SOFA, but due to the complexity of APACHE II and SAPS II calculations, OASIS is a good substitute. TRIAL REGISTRATION: This study was registered at www.chictr.org.cn (registration number Chi CTR-ONC-11001875). Registered on 14 December 2011.

Novel Diffusion-Weighted Imaging Score Showed Good Prognostic Value for Acute Basilar Artery Occlusion Following Endovascular Treatment: The Pons-Midbrain and Thalamus Score.

BACKGROUND AND PURPOSE: Prognostic factors for outcome of endovascular treatment remains to be investigated in patients with acute basilar artery occlusion. We aimed to assess the prognostic value of a novel pretreatment diffusion-weighted imaging score: The Pons-Midbrain and Thalamus (PMT) score. METHODS: Eligible patients who underwent endovascular treatment due to acute basilar artery occlusion were reviewed. The PMT score was a diffusion-weighted imaging-based semiquantitative scale in which the infarctions of pons, midbrain, and thalamus were fully considered. The PMT score was assessed as well as the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score and Brain Stem Score. Good outcomes were defined as a modified Rankin Scale score of ≤3 at 90-day and successful reperfusion as Thrombolysis in Cerebral Infarction grades 2b/3. The associations between baseline clinical parameters and good outcomes were evaluated with logistic regression. RESULTS: A total of 107 patients with pretreatment magnetic resonance imaging were included in this cohort. The baseline PMT score (median [interquartile range], 3 [1-5] versus 7 [5-9]; P<0.001) and Brain Stem Score (median [interquartile range], 2 [1-4] versus 3 [2-5]; P=0.001) were significantly lower in good outcome group; the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score was higher in good outcome group without statistical significance. As a result of receiver operating characteristic curve analyses, the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score showed poor prognostic accuracy for good outcome (area under the curve, 0.60 [95% CI, 0.49-0.71]; P=0.081); The baseline PMT score showed significantly better prognostic accuracy for 90-day good outcome than the Brain Stem Score and National Institutes of Health Stroke Scale (area under the curve, 0.80 versus 0.68 versus 0.78, P=0.003). In addition, favorable PMT score <7 (odds ratio, 22.0 [95% CI, 6.0-80.8], P<0.001), Brain Stem Score <3 (odds ratio, 4.65 [95% CI, 2.05-10.55], P<0.001) and baseline National Institutes of Health Stroke Scale <23 (odds ratio, 8.0 [95% CI, 2.5-25.6], P<0.001) were associated with improved good outcome. CONCLUSIONS: In patients with acute basilar artery occlusion following endovascular treatment, the pretreatment diffusion-weighted imaging based PMT score showed good prognostic value for clinical outcome.

Risk factors, clinical features and outcome of new-onset acute kidney injury among critically ill patients: a database analysis based on prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) newly-emerged in intensive care unit (ICU), has not been thoroughly studied in previous researches, is likely to differ from AKI developed before ICU admission. This study aimed to evaluate the incidence, risk factors, clinical features and outcome of new-onset AKI in critically ill patients. METHODS: The data of present study derived from a multicenter, prospective cohort study in17 Chinese ICUs (January 2014 - August 2015). The incidence, risk factors, clinical features and survival analysis of new-onset AKI were assessed. RESULTS: A total of 3374 adult critically ill patients were eligible. The incidence of new-onset AKI was 30.0 % (n = 1012). Factors associated with a higher risk of new-onset AKI included coronary heart disease, hypertension, chronic liver disease, use of nephrotoxic drugs, sepsis, SOFA score, APACHEII score and use of vasopressors. The new-onset AKI was an independent risk factor for 28-day mortality (adjusted hazard ratio, 1.643; 95 % CI, 1.370-1.948; P < 0.001). 220 (21.7 %) patients received renal replacement therapy (RRT), 71 (32.3 %) of them were successfully weaning from RRT. More than half of the new-onset AKI were transient AKI (renal recovery within 48 h). There was no statistical relationship between transient AKI and 28-day mortality (hazard ratio, 1.406; 95 % CI, 0.840-1.304; P = 0.686), while persistent AKI (non-renal recovery within 48 h) was strongly associated with 28-day mortality (adjusted hazard ratio, 1.486; 95 % CI, 1.137-1.943; P < 0.001). CONCLUSIONS: New-onset AKI is common in ICU patients and is associated with significantly higher 28-day mortality. Only persistent AKI, but not transient AKI is associated with significantly higher 28-day mortality.

Association between the modified Nutrition Risk in Critically Ill (mNUTRIC) score and clinical outcomes in the intensive care unit: a secondary analysis of a large prospective observational study.

BACKGROUND: Malnutrition in intensive care unit (ICU) patients is associated with adverse clinical outcomes. The modified nutrition risk in the critically ill score (mNUTRIC) was proposed as an appropriate nutritional assessment tool in critically ill patients, but it has not been fully demonstrated and widely used. Our study was conducted to identify the nutritional risk in ICU patients using the mNUTRIC score and explore the relationship between 28-day mortality and high mNUTRIC scores. METHODS: This study is a secondary analysis, the data were extracted from The Beijing Acute Kidney Injury Trial (BAKIT). In total, 9049 patients were admitted consecutively, and 3107 patients with complete clinical data were included in this study. We divided the study population into high nutritional risk (mNUTRIC score ≥ 5 points) and low nutritional risk (mNUTRIC score < 5 points) groups. The predictive capacity of the mNUTRIC score was studied by receiver operating characteristic (ROC) curve analysis, appropriate cut-off was identified by highest combined sensitivity and specificity using Youden's index. The significance level was set at 5%. RESULTS: Among the 3107 patients, the 28-day mortality rate was 17.4% (540 patients died). Nearly 28.2% of patients admitted to the ICU were at risk of malnutrition, high nutritional risk patients were older (P < 0.001), with higher illness severity scores than low nutritional risk patients. Multivariate analysis revealed that the mNUTRIC score was an independent risk factor for 28-day mortality and mortality increased with increasing scores (p = 0.000). The calculated area under curve (AUC) for the mNUTRIC score was 0.763 (CI 0.740-0.786). According to Youden's index, we found a suitable cut-off > 4 for the mNUTRIC score to predict the 28-day mortality. CONCLUSIONS: Patients admitted to the ICU were at high risk of malnutrition, and a high mNUTRIC score was associated with increased ICU length of stay and higher mortality. More large prospective studies are needed to demonstrate the validity of this score. TRIAL REGISTRATION: This study was registered at www.chictr.org.cn (registration number Chi CTR-ONC-11001875 ). Registered on 14 December 2011.

The maize SUMO conjugating enzyme ZmSCE1b protects plants from paraquat toxicity.

Paraquat (PQ) herbicide causes damage to green plant tissues by inducing the production of toxic reactive oxygen species (ROS). SUMOylation is an important post-translational modification that enables plants to defend against multiple stresses. However, it is still unknown whether the SUMOylation is involved in PQ resistance response in crops. Herein, we showed that a maize SUMO conjugating enzyme gene (ZmSCE1b) functioned in PQ resistance. The quantitative real-time PCR (qRT-PCR) analysis revealed that this gene was significantly up-regulated upon PQ exposure. The overexpression of ZmSCE1b increased the levels of SUMO conjugates and improved PQ resistance in transgenic Arabidopsis. The ZmSCE1b-transgenic plants showed lower levels of ROS and lipid peroxidation, as well as higher antioxidant enzyme activities, upon PQ exposure. Furthermore, Western blotting showed that levels of SUMOylation in these transgenic plants were significantly elevated. In addition, the abundance of transcripts of several defense-related genes was apparently up-regulated in the over-expressing lines using qRT-PCR. Collectively, our results manifested the effect of overexpression of ZmSCE1b in improving resistance to PQ, possibly by regulating the levels of SUMO conjugates, antioxidant machinery, and expression of defense genes. Findings of this study can facilitate the understanding of the regulatory mechanisms underlying the involvement of SCE-mediated SUMOylation in PQ resistance response in crop plants. Meanwhile, ZmSCE1b could be utilized for engineering PQ-resistant crops in phytoremediation.

Elevated triglyceride-glucose (TyG) index predicts incidence of Prediabetes: a prospective cohort study in China.

BACKGROUND: Prediabetes has become a pandemic. This study aimed to identify a better predictor for the incidence of prediabetes, which we hypothesize to be the triglyceride-glucose (TyG) index, a simplified insulin resistance index. We compared its predictive value with the other common risk factors of prediabetes. METHODS: The participants of this analysis were derived from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. A total of 4543 participants without initial prediabetes or diabetes were followed up for 3.25 years. Using multivariate logistic regression model, the associations between baseline obesity, lipid profiles and non-insulin-based insulin resistance indices with the incidence of prediabetes were analyzed. To assess which is better predictor for the incidence of prediabetes, the area under curves (AUCs) calculated from the receiver operating characteristic curve analyses were used to evaluate and compare with the predictive value of the different indices. RESULTS: During the 3.25 years, 1071 out of the 4543 participants developed prediabetes. Using the logistic regression analysis adjusted for some potential confounders, the risk of incidence of prediabetes increased 1.38 (1.28-1.48) fold for each 1-SD increment of TyG index. The predictive ability (assessed by AUCs) of TyG index for predicting prediabetes was 0.60 (0.58-0.62), which was superior to the indices of obesity, lipid profiles and other non-insulin-based insulin resistance indices. Although the predictive ability of the TyG index was overall similar to fasting plasma glucose (FPG) (P = 0.4340), TyG index trended higher than FPG in females (0.62 (0.59-0.64) vs. 0.59 (0.57-0.61), P = 0.0872) and obese subjects (0.59 (0.57-0.62) vs. 0.57 (0.54-0.59), P = 0.1313). TyG index had superior predictive ability for the prediabetic phenotype with isolated impaired glucose tolerance compared with FPG (P <  0.05) and other indices. Furthermore, TyG index significantly improved the C statistic (0.62 (0.60-0.64)), integrated discrimination improvement (1.89% (1.44-2.33%)) and net reclassification index (28.76% (21.84-35.67%)) of conventional model in predicting prediabetes than other indices. CONCLUSIONS: TyG could be a potential predictor to identify the high risk individuals of prediabetes.

The Arabidopsis APR2 positively regulates cadmium tolerance through glutathione-dependent pathway.

Cadmium (Cd) is a dangerous environmental pollutant with high toxicity to plants. The adenosine 5'-phosphosulfate reductase 2 (APR2) is the dominant APRs in Arabidopsis and plays an important role in reductive sulfate assimilation pathway. However, whether the involvement of plant APRs in Cd stress response is largely unclear. Herein, we report that APR2 functions in Cd accumulation and tolerance in Arabidopsis. The transcript levels of APR2 were markedly induced by Cd exposure. Transgenic plants overexpressing APR2 improved Cd tolerance, whereas knockout of APR2 reduced Cd tolerance. APR2-overexpressing plants with increased Cd accumulation and tolerance showed higher glutathione (GSH) and phytochelatin (PC) levels than the wild type and apr2 mutant plants, but lower H2O2 and TBARS contents upon Cd exposure. Moreover, exogenous GSH application effectively rescued Cd hypersensitivity in APR2-knockout plants. Further analysis showed that buthionine sulfoximine (BSO, an inhibitor of GSH synthesis) treatment completely eliminated the enhanced Cd tolerance phenotypes of APR2-overexpressing plants, implying that APR2-mediated enhanced Cd tolerance is GSH dependent. In addition, over-expression of the APR2 led to elevated expressions of the GSH/PC synthesis-related genes under Cd stress. Taken together, our results indicated that APR2 regulated Cd accumulation and tolerance possibly through modulating GSH-dependent antioxidant capability and Cd-chelation machinery in Arabidopsis. APR2 could be exploited for engineering heavy metal-tolerant plants in phytoremediation.

Matrine promotes apoptosis in SW480 colorectal cancer cells via elevating MIEF1-related mitochondrial division in a manner dependent on LATS2-Hippo pathway.

Matrine, an alkaloid compound isolated from Sophora flavescens Ait, has been shown to exert cancer-killing actions in a variety of tumors; however, its anticancer mechanism in colorectal cancer (CRC) is not clear. The goal of our study was to characterize the anticancer effects and molecular mechanisms of matrine in SW480 CRC cells in vitro. Matrine treatment reduced mitochondrial metabolic function and ATP levels, repressed mitochondrial membrane potential, evoked mitochondrial reactive oxygen species accumulation, and promoted cyt-c-related mitochondrial apoptosis activation. In addition, we found that matrine treatment activated mitochondrial fission through upregulating mitochondrial elongation factor 1 (MIEF1); silencing of MIEF1 prevented matrine-mediated mitochondrial damage and reversed the decrease in SW480 cell viability. Moreover, matrine treatment affected MIEF1 expression via the large tumor suppressor-2 (LATS2)-Hippo axis, and LATS2 deficiency suppressed the anticancer actions exerted by matrine on SW480 cancer cells. In summary, we show for the first time that matrine inhibits SW480 cell survival by activating MIEF1-related mitochondrial division via the LATS2-Hippo pathway. These findings explain the anticancer mechanisms of matrine in CRC and also identify the LATS2-MIEF1 signaling pathway as an effective target for the treatment of CRC.

Epidemiology of acute kidney injury in intensive care units in Beijing: the multi-center BAKIT study.

BACKGROUND: Acute kidney injury (AKI) commonly occurs in intensive care units (ICUs), leading to adverse clinical outcomes and increasing costs. However, there are limited epidemiological data of AKI in the critically ill in Beijing, China. METHODS: In this prospective cohort study in 30 ICUs, we screened the patients up to 10 days after ICU admission. Characteristics and outcomes were compared between AKI and non-AKI, renal replacement therapy (RRT) and non-RRT patients. Nomograms of logistic regression and Cox regression were performed to examine potential risk factors for AKI and mortality. RESULTS: A total of 3107 patients were included in the final analysis. The incidence of AKI was 51.0%; stages 1 to 3 accounted for 23.1, 11.8, and 15.7%, respectively. The majority (87.6%) of patients with AKI developed AKI on the first 4 days after admission to the ICU. A total of 281 patients were treated with RRT. Continuous RRT with predilution, citrate for anticoagulation and femoral vein for vascular access was the most common RRT pattern (29.9%, 84 of 281). Patients with AKI were associated with longer ICU-LOS and higher mortality and costs (P<0.001). In patients treated with RRT, 78.6 and 28.5% of RRTs were dependent on the 7th and 28th days, respectively. The 28 day mortalities of non-AKI, AKI stages 1-3, and septic shock patients were 6.83, 15.04, 27.99, 45.18 and 36.5%, respectively. CONCLUSIONS: Approximately half of our ICU patients experienced AKI. The majority of patients with AKI developed AKI during the first 4 days after admission to the ICU. Continuous RRT with predilution, citrate for anticoagulation and femoral vein for vascular access was the most common RRT pattern in our ICUs. AKI was associated with a higher mortality and costs, incomplete kidney recovery and s series of adverse outcomes.

The Maize Class-I SUMO Conjugating Enzyme ZmSCE1d Is Involved in Drought Stress Response.

Post-translational modification of cellular proteins by sumoylation plays a vital role in stress responses of plants. However, the mechanisms underlying the sumoylation's involvement in stress responses in crop species remain largely unknown. Herein, a maize class-I SUMO conjugating enzyme gene (ZmSCE1d) was identified, whose expression was upregulated upon drought stress. Over-expression of ZmSCE1d in transgenic Arabidopsis plants increased SUMO conjugates and improved drought tolerance. The ZmSCE1d-transgenic plants showed higher antioxidant enzyme activities, but lower reactive oxygen species and lipid peroxidation upon drought stress. Furthermore, transcripts of several drought-responsive genes were significantly elevated, as revealed by qPCR in the transgenic lines. Taken together, these data have demonstrated that ZmSCE1d overexpression improved drought tolerance likely by regulating sumoylation levels, antioxidant capability, and drought-responsive gene expression in transgenic plants. This study may facilitate our understanding of the mechanisms underlying SCE-mediated sumoylation under drought stress and accelerate genetic improvement of crop plants tolerant to drought stress by manipulating the SUMO system.