Biochar effects on salt-affected soil properties and plant productivity: A global meta-analysis.

Biochar has been recognized as a promising practice for ameliorating degraded soils, yet the consensus on its effects remains largely unknown due to the variability among biochar, soil and plant. This study therefore presents a meta-analysis synthesizing 92 publications containing 987 paired data to scrutinize biochar effects on salt-affected soil properties and plant productivity. Additionally, a random meta-forest approach was employed to identify the key factors of biochar on salt-affected soil and plant productivity. Results showed that biochar led to significant reductions in electrical conductivity (EC), bulk density (BD) and pH by 7.4%, 4.7% and 1.2% compared to the unamended soil, respectively. Soil organic carbon (by 55.1%) and total nitrogen (by 31.3%) increased significantly with biochar addition. Moreover, biochar overall enhanced plant productivity by 31.5%, and more pronounced increases in forage/medicinal with higher salt tolerance than others. The results also identified that the soil salinity and biochar application rate were the most important co-regulators for EC and PP changes. The structural equation model further showed that soil salinity (P < 0.001), biochar pH (P < 0.001) and biochar specific surface area (P < 0.01) had a significant negative effect on soil EC, but it was positively impacted by biochar pyrolysis temperature (P < 0.05). Furthermore, plant productivity was positively affected by biochar pH (P < 0.001) and biochar feedstock (P < 0.01), while negatively influenced by biochar pyrolysis temperature (P < 0.01). This study highlights that woody biochar with 7.6 < pH < 9.0 and pyrolyzed at 400-600 °C under 30-70 t ha-1 application rate in moderately saline coarse soils is a recommendable pattern to enhance forage/medicinal productivity while reducing soil salinity. In conclusion, biochar offers promising avenues for ameliorating degradable soils, but it is imperative to explore largescale applications and field performance across different biochar, soil, and plant types.

Integrated nonstationary and uncertain analysis of coupled relationship of hydrological connectivity and water level in a highly fragmented wetland.

Understanding the relationship between hydrological connectivity (HC) and water level (WL) is crucial for effective water resource management and wetland restoration. However, current knowledge regarding this relationship is limited. This study proposed an integrated nonstationary and uncertain analysis framework (INUAF) to investigate the HC-WL relationship with reference to the Baiyangdian wetland, which is a fragmented wetland in North China. With the INUAF, the interannual and intra-annual variations of both HC and WL were examined, together with the wavelet coherence and lag effects between the two variables at multiple scales. The results highlighted marked nonstationarity in HC, WL, and the relationship between them. Scale-dependent lag effects revealed that HC lags WL by 37 days (131 days) at the 1 a scale (4 a scale), and leads WL by 190 days at the 8 a scale, indicating a complex coupled relationship between HC and WL. Additionally, the INUAF was applied to evaluating the uncertainty in the response of lagged HC to varied WL. Results indicated that every 0.2-m increase in WL led to a 2.2%-2.4% higher probability of maintaining high HC for WL between 6.0 and 8.0 m, but a 10%-11% higher probability for WL between 8.0 and 9.0 m. We suggest that a WL of > 8.4 m would produce a probability of > 50% for achieving high HC. These findings provide valuable insights into the HC-WL relationship and could contribute to wetland restoration efforts.

Exendin-4 ameliorates tau hyperphosphorylation and cognitive impairment in type 2 diabetes through acting on Wnt/ß-catenin/NeuroD1 pathway.

BACKGROUND: Type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD). Exendin-4 (Ex-4), a widely used glucagon-like peptide-1 receptor agonist drug in the treatment of T2D, has been demonstrated the therapeutic effects on diabetic encephalopathy (DE). Especially, the Ex-4 ameliorates the tau hyperphosphorylation and cognitive impairment in DE. And these crucial alterations are also important bridge between T2D and AD. However, its unique mechanism is unclear. METHODS: The db/db mice, high-fat-diet (HFD) / streptozotocin (STZ)-induced diabetic (HF-diabetic) mice, and high-glucose-damaged (HGD) HT-22 hippocampal cells were enrolled to examine the effects of Ex-4 on AD-like changes in T2D. The Novel object recognition test (NORT) and Morris water maze test (MWMT) were conducted to evaluate the cognitive impairment. The Dickkopf-1 (DKK1) was employed to weaken the activation of the Wnt/ß-catenin pathway to explore the mechanism of Ex-4 in protecting the brain functions. The JASPAR was based to predict the interaction between NeuroD1 and the promoter region of Ins2. Moreover, the chromatin immunoprecipitation coupled with quantitative polymerase chain reaction (ChIP-qPCR) and luciferase reporter assays were performed. RESULTS: Ex-4 alleviated the tau hyperphosphorylation, increased the brain-derived insulin, and improved the PI3K/AKT/GSK3-ß signalling in db/db mice, HF-diabetic mice, and HGD HT-22 hippocampal neuronal cells. The NORT and MWMT indicated that Ex-4 alleviated the learning and memory deficits in HF-diabetic mice. The inhibitor Dickkopf-1 (DKK1) of the Wnt/ß-catenin pathway significantly blocked the protective effects of Ex-4. Regarding further molecular mechanisms, NeuroD1 was affected by Ex-4 in vivo and in vitro, and the knockdown or overexpression of NeuroD1 suggested its crucial role in promoting the brain insulin by Ex-4. Meanwhile, the ChIP‒qPCR and luciferase reporter assays confirmed the combination between NeuroD1 and the promoter region of the insulin-encoding gene Ins2. And this interaction could be promoted by Ex-4. CONCLUSIONS: Our study proposes that Ex-4 alleviates tau hyperphosphorylation and cognitive dysfunction by increasing Ins2-derived brain insulin through the Wnt/ß-catenin/NeuroD1 signaling in T2D. And its also show new lights on part of the progress and mechanism on treatment targets for the DE in T2D.

A region-specific modulation of sleep slow waves on interictal epilepsy markers in focal epilepsy.

OBJECTIVE: Sleep strongly activates interictal epileptic activity through an unclear mechanism. We investigated how scalp sleep slow waves (SSWs), whose positive and negative half-waves reflect the fluctuation of neuronal excitability between the up and down states, respectively, modulate interictal epileptic events in focal epilepsy. METHODS: Simultaneous polysomnography was performed in 45 patients with drug-resistant focal epilepsy during intracranial electroencephalographic recording. Scalp SSWs and intracranial spikes and ripples (80-250 Hz) were detected; ripples were classified as type I (co-occurring with spikes) or type II (occurring alone). The Hilbert transform was used to analyze the distributions of spikes and ripples in the phases of SSWs. RESULTS: Thirty patients with discrete seizure-onset zone (SOZ) and discernable sleep architecture were included. Intracranial spikes and ripples accumulated around the negative peaks of SSWs and increased with SSW amplitude. Phase analysis revealed that spikes and both ripple subtypes in SOZ were similarly facilitated by SSWs exclusively during down state. In exclusively irritative zones outside SOZ (EIZ), SSWs facilitated spikes and type I ripples across a wider range of phases and to a greater extent than those in SOZ. The type II and type I ripples in EIZ were modulated by SSWs in different patterns. Ripples in normal zones decreased specifically during the up-to-down transition and then increased after the negative peak of SSW, with a characteristically high post-/pre-negative peak ratio. SIGNIFICANCE: SSWs modulate interictal events in an amplitude-dependent and region-specific pattern. Pathological ripples and spikes were facilitated predominantly during the cortical down state. Coupling analysis of SSWs could improve the discrimination of pathological and physiological ripples and facilitate seizure localization.

The relationship between red blood cell distribution width and islet ß-cell function indexes in patients with latent autoimmune diabetes in adults.

AIMS: The objective of this study is to explore the relationship between red blood cell distribution and islet ß-cell function indexes in patients with Latent Autoimmune Diabetes in Adults. METHODS: A total of 487 LADA patients were enrolled in this cross-sectional study. Patients were divided into three groups according to RDW tertiles. Clinical and laboratory measurements of age, height, weight, duration of diabetes, blood pressure, RDW, glycosylated hemoglobin A1c (HbA1c), C-peptide and blood lipids were performed. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ß-cell function (HOMA-ß) were assessed using homeostasis model assessment (HOMA) based on fasting blood glucose (FBG) and fasting C-peptide index (FCP). Correlations and multiple linear regressions were implemented to determine the association of RDW and islet function indexes. RESULTS: As the increase of serum RDW level, the presence of ß-cell secretion increased(P < 0.05). Correlation analysis indicated that there were significant correlations between RDW and male sex, age, duration, TG, Cr, FCP, and HOMA-ß in all subjects. Multiple linear regressions indicated that RDW was significantly correlated with HOMA-ß in the total population in both unadjusted and adjusted analysis. This finding could be reproduced in the subgroup of low GAD titers for HOMA-ß. RDW were significantly associated with HbA1c in LADA patients with high GAD titers, but the correlation was not found in subgroup with low GAD titers in either unadjusted analyses or adjusted analysis. CONCLUSIONS: RDW is associated with ß-cell function assessed by HOMA-ß after adjusting for covariates in LADA patients with low GAD titers.

Association between a high triglyceride-glucose index and chronic kidney disease in adult patients with latent autoimmune diabetes.

BACKGROUND: Insulin resistance (IR) is one of the risk factors for chronic kidney disease (CKD) and diabetes. The triglyceride-glucose (TyG) index is considered a reliable alternative marker of IR. We investigated the correlation between the TyG index and the severity of CKD in patients with latent autoimmune diabetes in adults (LADA). METHODS: This cross-sectional study included 288 patients with LADA in the department of endocrinology at our hospital between January 2018 and January 2022. The TyG index was calculated as Ln [TG (mg/dl) × fasting blood glucose (FBG) (mg/dl) / 2]. All individuals were divided into either a LADA + CKD group or a LADA + non-CKD group according to the presence or absence of CKD. A correlation analysis, logistic regression analysis and receiver operating characteristics curve analysis were performed. RESULTS: A total of 130 (45.1%) participants were identified as having CKD. Compared with the non-CKD group, the CKD group had a longer disease duration and a higher proportion of smokers; patients were more likely to have hypertension and higher serum creatinine, triglyceride, cholesterol, low-density lipoprotein cholesterol, FBG, uric acid estimated glomerular filtration rates (eGFR) and TyG levels as well as lower high-density lipoprotein cholesterol levels (all P < 0.05). The positive relationship between the TyG index and the urinary albumin/creatinine ratio was significant (r = 0.249, P = 0.010). There was also a significant correlation between the TyG index and the eGFR (r = - 0.211, P = 0.034) after adjusting for confounding factors. The area-under-the-curve value of the TyG index was 0.708 (95% confidence interval: 0.61-0.81, P < 0.001). CONCLUSIONS: The TyG index is significantly associated with the severity of CKD in patients with LADA. This conclusion supports the clinical application of the TyG index for the assessment of kidney disease in patients with LADA.

Correlation between the platelet-to-lymphocyte ratio and diabetic foot ulcer in patients with type 2 diabetes mellitus.

OBJECTIVE: To investigate the correlation between the platelet-to-lymphocyte ratio (PLR) and diabetic foot ulcer (DFU) in patients with type 2 diabetes mellitus (T2DM). METHOD: From January 2018 to August 2019, 206 patients with T2DM admitted to the Central Hospital of Wuhan, China, were enrolled in this study, including 104 patients with DFU (DFU group) and 102 patients without DFU (T2DM group). During the same period, 90 healthy subjects were randomly screened as normal controls (NC group). The correlation between PLR and DFU in patients with T2DM was explored by comparing the PLR of the subjects in the three groups. RESULTS: The PLRs of the DFU and T2DM groups were higher than that of the NC group, whereas the PLR of the DFU group was higher than that of the T2DM group (p < 0.05). PLR was positively correlated with the Wagner DFU grade (p < 0.001). Based on logistic regression analysis, PLR was found to be an independent risk factor for DFU (OR =1.029, 95% CI: 1.019 ~ 1.039, p < 0.001). The receiver operating characteristic curve analysis of the PLR showed that the area under the curve of the PLR for predicting diabetic foot ulcer was 0.776 (p < 0.001), and the analysis determined that the optimal critical value of the PLR for predicting DFU was 147.6. CONCLUSION: The PLR is significantly elevated in patients with DFU and positively correlated with the Wagner DFU grade, which might be a valuable marker for early diagnosis and assessment of severity of DFU.

Muscle-specific regulation of right ventricular transcriptional responses to chronic hypoxia-induced hypertrophy by the muscle ring finger-1 (MuRF1) ubiquitin ligase in mice.

BACKGROUND: We recently identified a role for the muscle-specific ubiquitin ligase MuRF1 in right-sided heart failure secondary to pulmonary hypertension induced by chronic hypoxia (CH). MuRF1-/- mice exposed to CH are resistant to right ventricular (RV) dysfunction whereas MuRF1 Tg + mice exhibit impaired function indicative of heart failure. The present study was undertaken to understand the underlying transcriptional alterations in the RV of MuRF1-/- and MuRF1 Tg + mice. METHODS: Microarray analysis was performed on RNA isolated from the RV of MuRF1-/-, MuRF1 Tg+, and wild-type control mice exposed to CH. RESULTS: MuRF1-/- RV differentially expressed 590 genes in response to CH. Analysis of the top 66 genes (> 2-fold or < - 2-fold) revealed significant associations with oxidoreductase, transcription regulation, and transmembrane component annotations. The significant genes had promoters enriched for HOXD12, HOXC13, and RREB-1 protein transcription factor binding sites. MuRF1 Tg + RV differentially expressed 150 genes in response to CH. Analysis of the top 45 genes (> 3-fold or < - 3-fold) revealed significant associations with oxidoreductase-metabolic, glycoprotein-transmembrane-integral proteins, and alternative splicing/splice variant annotations. The significant genes were enriched for promoters with ZIC1 protein transcription factor binding sites. CONCLUSIONS: The differentially expressed genes in MuRF1-/- and MuRF1 Tg + RV after CH have common functional annotations related to oxidoreductase (including antioxidant) and transmembrane component functions. Moreover, the functionally-enhanced MuRF1-/- hearts regulate genes related to transcription, homeobox proteins, and kinases/phosphorylation. These studies also reveal potential indirect effects of MuRF1 through regulating Rreb-1, and they reveal mechanisms by which MuRF1 may transcriptionally regulate anti-oxidant systems in the face of right heart failure.

Eco-compensation in China: Theory, practices and suggestions for the future.

Eco-compensation is the most important form of compensatory conservation in China. However, this compensatory mechanism is criticized for vague definition and massive government participation. For better understanding of eco-compensation in China, this paper compares theories and practices of compensatory mechanisms in China and abroad. The analysis of theoretical backgrounds shows that eco-compensation in China is a combination of 'ecological compensation' and 'payments for ecosystem services'. Ten compensatory projects in China and abroad are assessed to reveal characteristics and problems of eco-compensation in China. The results show that compensatory projects in China lagged behind mature foreign compensatory projects in clarity of property rights, responsibility fulfillment, executive efficiency, effectiveness, sustainability and equality. The massive participation of the government is the major reason for the poor performance of compensatory projects in China. However, government participation is necessary at the present stage in China for the income gap and beneficiaries' low willingness to pay. For the improvement of eco-compensation in China, suggestions are given on the choice of non-market valuation methods, the creation of property rights and the establishment of market mechanisms.

BRG1 and BRM function antagonistically with c-MYC in adult cardiomyocytes to regulate conduction and contractility.

RATIONALE: The contractile dysfunction that underlies heart failure involves perturbations in multiple biological processes ranging from metabolism to electrophysiology. Yet the epigenetic mechanisms that are altered in this disease state have not been elucidated. SWI/SNF chromatin-remodeling complexes are plausible candidates based on mouse knockout studies demonstrating a combined requirement for the BRG1 and BRM catalytic subunits in adult cardiomyocytes. Brg1/Brm double mutants exhibit metabolic and mitochondrial defects and are not viable although their cause of death has not been ascertained. OBJECTIVE: To determine the cause of death of Brg1/Brm double-mutant mice, to test the hypothesis that BRG1 and BRM are required for cardiac contractility, and to identify relevant downstream target genes. METHODS AND RESULTS: A tamoxifen-inducible gene-targeting strategy utilizing αMHC-Cre-ERT was implemented to delete both SWI/SNF catalytic subunits in adult cardiomyocytes. Brg1/Brm double-mutant mice were monitored by echocardiography and electrocardiography, and they underwent rapidly progressive ventricular dysfunction including conduction defects and arrhythmias that culminated in heart failure and death within 3weeks. Mechanistically, BRG1/BRM repressed c-Myc expression, and enforced expression of a DOX-inducible c-MYC trangene in mouse cardiomyocytes phenocopied the ventricular conduction defects observed in Brg1/Brm double mutants. BRG1/BRM and c-MYC had opposite effects on the expression of cardiac conduction genes, and the directionality was consistent with their respective loss- and gain-of-function phenotypes. To support the clinical relevance of this mechanism, BRG1/BRM occupancy was diminished at the same target genes in human heart failure cases compared to controls, and this correlated with increased c-MYC expression and decreased CX43 and SCN5A expression. CONCLUSION: BRG1/BRM and c-MYC have an antagonistic relationship regulating the expression of cardiac conduction genes that maintain contractility, which is reminiscent of their antagonistic roles as a tumor suppressor and oncogene in cancer.

Depletion of PHD3 protects heart from ischemia/reperfusion injury by inhibiting cardiomyocyte apoptosis.

PHD3, a member of a family of Prolyl-4 Hydroxylase Domain (PHD) proteins, has long been considered a pro-apoptotic protein. Although the pro-apoptotic effect of PHD3 requires its prolyl hydroxylase activity, it may be independent of HIF-1α, the common substrate of PHDs. PHD3 is highly expressed in the heart, however, its role in cardiomyocyte apoptosis remains unclear. This study was undertaken to determine whether inhibition or depletion of PHD3 inhibits cardiomyocyte apoptosis and attenuates myocardial injury induced by ischemia-reperfusion (I/R). PHD3 knockout mice and littermate controls were subjected to left anterior descending (LAD) coronary artery ligation for 40 min followed by reperfusion. Histochemical analysis using Evan's Blue, triphenyl-tetrazolium chloride and TUNEL staining, demonstrated that myocardial injury and cardiomyocyte apoptosis induced I/R injury were significantly attenuated in PHD3 knockout mice. PHD3 knockout mice exhibited no changes in HIF-1α protein level, the expression of some HIF target genes or the myocardium capillary density at physiological condition. However, depletion of PHD3 further enhanced the induction of HIF-1α protein at hypoxic condition and increased expression of HIF-1α inhibited cardiomyocyte apoptosis induced by hypoxia. In addition, it has been demonstrated that PHD3 plays an important role in ATR/Chk1/p53 pathway. Consistently, a prolyl hydroxylase inhibitor or depletion of PHD3 significantly inhibits the activation of Chk1 and p53 in cardiomyocytes and the subsequent apoptosis induced by doxorubicin, hydrogen peroxide or hypoxia/reoxygenation. Taken together, these data suggest that depletion of PHD3 leads to increased stabilization of HIF-1α and inhibition of DNA damage response, both of which may contribute to the cardioprotective effect seen with depletion of PHD3.

Association of height with peripheral arterial disease in type 2 diabetes.

OBJECTIVE: To investigate whether height is associated with peripheral arterial disease (PAD) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was an observational study performed in 4,528 Chinese patients with type 2 diabetes. Anthropometric measures and the ankle-brachial index (ABI) were performed on each subject. PAD was defined as those patients with a history of revascularization or amputation due to ischemia, or an ABI <0.9. RESULTS: A total of 23.3 % of T2DM patients had PAD (men 22.9 % and women 23.7 %). The mean age and height were 57.8 ± 12.5 years and 170.5 cm for men, and 60.0 ± 11.7 years and 158.9 cm for women, respectively. The ABI and frequency of PAD were higher with decreasing height quartiles. An inverse association was observed between height- and gender-adjusted risk of PAD. This relationship remained unchanged following further adjustment for potential confounders. Subjects in the shortest stature group had of 1.174 times higher risk of PAD for men and 1.143 times for women, compared with those in the tallest stature group. The multivariate adjusted hazard ratios (95 % CI) of PAD for a 10-cm height increase were 0.85 (95 % CI 0.78-0.94). CONCLUSION: A short stature seems to be associated with higher risk of PAD in Chinese diabetic patients. However, the cross-sectional nature of the study limits conclusions regarding the direction or causality. Further longitudinal study is warranted in this and other ethnic groups.

Improved remote sensing reference evapotranspiration estimation using simple satellite data and machine learning.

Reference evapotranspiration (ET0) estimation is crucial for efficient irrigation planning, optimized water management and ecosystem modeling, yet it presents significant challenges, particularly when meteorological data availability is limited. This study utilized remote sensing data of land surface temperature (LST), day of year, and latitude, and employed a machine learning approach (i.e., random forest) to develop an improved remote sensing ET0 model. The model performed excellently in 567 meteorological stations in China with an R2 of 0.97, RMSE of 0.40, MBE of 0.00, and MAPE of 0.11 compared to the FAO-PM ET0; it also performed well globally, yielding an average R2 of 0.97 and RMSE of 0.43 across 120 sites in mid-latitude (20°-50°) regions. This model demonstrates simplicity, accuracy, robust and generalization, holding great potential for widespread application, especially in the large-scale, high-resolution estimation of ET0. This study will contribute to advancements in water resources management, agricultural planning, and climate change studies.

Myeloid-derived growth factor and its effects on cardiovascular and metabolic diseases.

Myeloid-derived growth factor (MYDGF) is a paracrine protein produced by bone marrow-derived monocytes and macrophages. Current research shows that it has protective effects on the cardiovascular system, such as repairing heart tissue after myocardial infarction, enhancing cardiomyocyte proliferation, improving cardiac regeneration after myocardial injury, regulating proliferation and survival of endothelial cells, reducing endothelial cell damage, resisting pressure overload-induced heart failure, as well as protecting against atherosclerosis. Furthermore, regarding the metabolic diseases, MYDGF has effects of improving type 2 diabetes mellitus, relieving non-alcoholic fatty liver disease, alleviating glomerular diseases, and resisting osteoporosis. Herein, we will discuss the biology of MYDGF and its effects on cardiovascular and metabolic diseases.

The clinical and genetic characteristics of maternally inherited diabetes and deafness (MIDD) with mitochondrial m.3243A > G mutation: A 10-year follow-up observation study and literature review.

Maternally inherited diabetes and deafness (MIDD) is often caused by the m.3243A > G mutation in mitochondrial DNA. Unfortunately, the characteristics of MIDD, especially long-term outcomes and heteroplasmic changes, have not been well described previously. The purpose of this study was to describe the clinical and genetic features of a family with MIDD after 10 years of follow-up.A 33-year-old male patient with typical characteristics of MIDD, including early-onset diabetes, deafness, and low body mass index, was admitted to our department. Further investigation revealed that the vast majority of his maternal relatives suffered from diabetes with or without deafness. A detailed family history was then requested from the patient and a pedigree was constructed. The patient suspected of MIDD was screened for mutations using whole mitochondrial DNA sequencing. Candidate pathogenic variants were then validated in other family members through Sanger sequencing. The patient was diagnosed with MIDD, with inherited m.3243A > G mutation in the mitochondrially encoded tRNA leucine 1 (MT-TL1) gene, after 10 years of symptom onset. The patient was then treated with insulin and coenzyme Q10 to improve mitochondrial function. During the follow-up period, his fasting blood glucose and HbA1c levels were improved and the incidence of diabetic ketoacidosis was significantly reduced. Our findings indicate that whole mitochondrial DNA sequencing should be considered for patients suspected of MIDD to improve the efficiency of diagnosis and prognosis.

Comparing administered and market-based water allocation systems through a consistent agent-based modeling framework.

Water allocation can be undertaken through administered systems (AS), market-based systems (MS), or a combination of the two. The debate on the performance of the two systems has lasted for decades but still calls for attention in both research and practice. This paper compares water users' behavior under AS and MS through a consistent agent-based modeling framework for water allocation analysis that incorporates variables particular to both MS (e.g., water trade and trading prices) and AS (water use violations and penalties/subsidies). Analogous to the economic theory of water markets under MS, the theory of rational violation justifies the exchange of entitled water under AS through the use of cross-subsidies. Under water stress conditions, a unique water allocation equilibrium can be achieved by following a simple bargaining rule that does not depend upon initial market prices under MS, or initial economic incentives under AS. The modeling analysis shows that the behavior of water users (agents) depends on transaction, or administrative, costs, as well as their autonomy. Reducing transaction costs under MS or administrative costs under AS will mitigate the effect that equity constraints (originating with primary water allocation) have on the system's total net economic benefits. Moreover, hydrologic uncertainty is shown to increase market prices under MS and penalties/subsidies under AS and, in most cases, also increases transaction, or administrative, costs.

Diagnostic Value of the Combined Measurement of Serum HCY and NRG4 in Type 2 Diabetes Mellitus with Early Complicating Diabetic Nephropathy.

PURPOSE: This study aimed to investigate the value of combined detection of HCY and NRG4 in the diagnosis of early diabetic kidney disease (DKD) and to explore the association between the ratio of HCY/NRG4 and DKD. METHODS: A total of 140 diabetic patients and 43 healthy people were prospectively enrolled. The plasma HCY level, NRG4 level and HCY/NRG4 of them were measured to compare their differences and analyze the correlation with DKD. The independent influencing factors of patients with DKD were screened, and the nomograph of DKD occurrence was constructed. RESULTS: The levels of HCY and HCY/NRG4 in diabetic patients were significantly increased, while the level of NRG4 was significantly decreased (p < 0.01). The AUCs of HCY/NRG4 predicted for DKD were 0.961. HCY/NRG4 and the course of DM were independent risk factors for DKD. A predictive nomograph of DKD was constructed, and decision curve analysis (DCA) showed good clinical application value. HCY/NRG4 was positively correlated with Scr, UACR, TG, UA, BUN, TCHOL and LDL and negatively correlated with eGFR and HDL (p < 0.05). CONCLUSIONS: The level of HCY and NRG4 is closely related to the severity of DM, and combined detection of HCY/NRG4 can identify patients with DKD at an early stage.

Endothelial expression of human cytochrome P450 epoxygenase CYP2C8 increases susceptibility to ischemia-reperfusion injury in isolated mouse heart.

Cytochrome P450 (CYP) epoxygenases CYP2C8 and CYP2J2 generate epoxyeicosatrienoic acids (EETs) from arachidonic acid. Mice with expression of CYP2J2 in cardiomyocytes (αMHC-CYP2J2 Tr) or treated with synthetic EETs have increased functional recovery after ischemia/reperfusion (I/R); however, no studies have examined the role of cardiomyocyte- vs. endothelial-derived EETs or compared the effects of different CYP epoxygenase isoforms in the ischemic heart. We generated transgenic mice with increased endothelial EET biosynthesis (Tie2-CYP2C8 Tr and Tie2-CYP2J2 Tr) or EET hydrolysis (Tie2-sEH Tr). Compared to wild-type (WT), αMHC-CYP2J2 Tr hearts showed increased recovery of left ventricular developed pressure (LVDP) and decreased infarct size after I/R. In contrast, LVDP recovery and infarct size were unchanged in Tie2-CYP2J2 Tr and Tie2-sEH Tr hearts. Surprisingly, compared to WT, Tie2-CYP2C8 Tr hearts had significantly reduced LVDP recovery (from 21 to 14%) and increased infarct size after I/R (from 51 to 61%). Tie2-CYP2C8 Tr hearts also exhibited increased reactive oxygen species (ROS) generation, dihydroxyoctadecenoic acid (DiHOME) formation, and coronary resistance after I/R. ROS scavengers and CYP2C8 inhibition reversed the detrimental effects of CYP2C8 expression in Tie2-CYP2C8 Tr hearts. Treatment of WT hearts with 250 nM 9,10-DiHOME decreased LVDP recovery compared to vehicle (16 vs. 31%, respectively) and increased coronary resistance after I/R. These data demonstrate that increased ROS generation and enhanced DiHOME synthesis by endothelial CYP2C8 impair functional recovery and mask the beneficial effects of increased EET production following I/R.

Recombinant human interleukin-11 treatment enhances collateral vessel growth after femoral artery ligation.

OBJECTIVE: To investigate the role of recombinant human interleukin-11 (rhIL-11) on in vivo mobilization of CD34(+)/vascular endothelial growth factor receptor (VEGFR) 2(+) mononuclear cells and collateral vessel remodeling in a mouse model of hindlimb ischemia. METHODS AND RESULTS: We observed that treatment of Sv129 mice with continuous infusion of 200-µg/kg rhIL-11 per day led to in vivo mobilization of CD34(+)/VEGFR2(+) cells that peaked at 72 hours. Sv129 mice pretreated with rhIL-11 for 72 hours before femoral artery ligation showed a 3-fold increase in plantar vessel perfusion, leading to faster blood flow recovery; and a 20-fold increase in circulating CD34(+)/VEGFR2(+) cells after 8 days of rhIL-11 treatment. Histologically, experimental mice had a 3-fold increase in collateral vessel luminal diameter after 21 days of rhIL-11 treatment and a 4.4-fold influx of perivascular CD34(+)/VEGFR2(+) cells after 8 days of therapy. Functionally, rhIL-11-treated mice showed better hindlimb appearance and use scores when compared with syngeneic mice treated with PBS under the same experimental conditions. CONCLUSIONS: These novel findings show that rhIL-11 promotes in vivo mobilization of CD34(+)/VEGFR2(+) mononuclear cells, enhances collateral vessel growth, and increases recovery of perfusion after femoral artery ligation. Thus, rhIL-11 has a promising role for development as an adjunctive treatment of patients with peripheral vascular disease.