Novel C4P2 monolayers: forming Z-scheme heterojunction and Janus structure for high-efficiency metal-free photocatalytic water splitting.

Metal-free two-dimensional (2D) semiconductors have garnered significant attention in the realm of photocatalytic water splitting, primarily owing to their inherent clean, stable, and efficient photoresponsive properties. Motivated by it, we have proposed two types of stable C4P2 monolayers with indirect band gaps, mediocre carrier mobility and excellent optical absorption in visible-light and ultraviolet regions. Although the too-low work function of monolayer α-C4P2 and the too-high work function of monolayer ß-C4P2 make them only suitable for single-side redox reaction in photocatalytic water splitting, the creation of an α-C4P2/ß-C4P2 Z-scheme heterojunction, combined with the Janus monolayer γ-C4P2 that integrates features of both α and ß structures, effectively addresses this limitation, fulfilling the prerequisites for comprehensive photocatalytic water splitting. Furthermore, the calculations indicate that the α-C4P2/ß-C4P2 Z-scheme heterojunction and Janus monolayer γ-C4P2 not only demonstrate improved carrier mobility and optical absorption but also feature internal electric fields that effectively enhance driving energy and photo-induced charge separation. Notably, Janus monolayer γ-C4P2 achieves a high electron mobility of ∼105 cm2 V-1 s-1 and an impressive solar-to-hydrogen conversion efficiency of 25.62%.

Super-high carrier mobilities and excellent thermoelectric performances of Tri-Tri group-VA monolayers.

High-performance thermoelectric materials in theoretical and experimental research are mostly composed of expensive, scarce, heavy elements and rarely of single light elements, which severely limit their application and development. Based on density functional and semiclassical Boltzmann transport theory, we determine that a stable phosphorene allotrope, named Tri-Tri phosphorene, has super-high electron mobility (23845.29 cm2 V-1 s-1) much higher than those of most two-dimension materials. Moreover, its optimized maximum ZT can reach up to 3.43 at room temperature (4.83 at 500 K and 5.92 at 700 K), exhibiting highly favorable prospects in practical thermoelectric systems. Motivated by the excellent properties of Tri-Tri phosphorene, we further demonstrate the structural stability of Tri-Tri arsenene and Tri-Tri antimonene and predict that the two Tri-Tri structures also have high Seebeck coefficients and electron mobilities. Their lattice thermal conductivities are dramatically decreased compared with Tri-Tri phosphorene. Thus, their predicted thermoelectric performances are also excellent, with maximum ZT values of 4.12 (Tri-Tri arsenene) and 3.54 (Tri-Tri antimonene) at room temperature. The low layer moduli of the three Tri-Tri structures indicate that they have high mechanical flexibility and suitability for current device assemblies. All these desirable properties make Tri-Tri group-VA materials promising for future applications in thermoelectric devices.

Metal-free Janus α- and ß-SiCP4: designing stable and efficient two-dimensional semiconductors for water splitting.

Two-dimensional (2D) semiconductors exhibit exceptional potential in the field of photocatalytic water splitting due to their unique structural characteristics and photoelectric properties. In this study, based on first-principles density functional theory, we theoretically proposed two SiCP4 Janus 2D semiconductors with high stability, namely monolayer α- and ß-SiCP4. By performing the calculation of HSE06 functionals, the band structures of monolayer α- and ß-SiCP4 have been estimated, and the results show that both α- and ß-SiCP4 are direct-band-gap semiconductors with band gaps of 1.64 eV and 1.91 eV, respectively. Meanwhile, the band edge levels of monolayer α- and ß-SiCP4 meet the band structure requirements of photocatalysts in water splitting. Notably, because of the internal build-in electric fields and tiny band gaps, monolayer α- and ß-SiCP4 exhibit separated photogenerated electron-hole pairs and high solar-to-hydrogen (STH) efficiency, reaching up to 33.68% and 23.72%, respectively. Additionally, we also investigate the impact of uniaxial strain on electronic, optical and photocatalytic properties of monolayer α- and ß-SiCP4 considering pH values ranging from 0 to 14. Our results demonstrate that the maximum STH efficiency for α-SiCP4 is achieved under X-direction strain (η) of 2%, Y-direction strain (η) of 8%, and pH values between 2 and 4. Conversely, ß-SiCP4 exhibits the highest STH efficiency under X-direction strain (η) of 8%, Y-direction strain (η) of 6%, and pH values between 2 and 4.

External validation of the AntiEpileptic Drug Monitoring in PREgnancy (EMPiRE) model for predicting seizures in pregnant women with epilepsy.

BACKGROUND: The AntiEpileptic Drug Monitoring in PREgnancy (EMPiRE) model is the only available tool for predicting seizures in pregnant women with epilepsy (WWE) using anti-seizure medications (ASMs); however, its predictive performance requires validation. This study aimed to evaluate the predictive ability of this model in pregnant Chinese WWE and its potential usefulness in clinical practice. METHODS: Data of the EMPiRE model were derived from the EMPiRE study, a prospective multicenter cohort study that recruited women on ASM monotherapy (lamotrigine, carbamazepine, phenytoin or levetiracetam) or polytherapy (lamotrigine with either carbamazepine, phenytoin or levetiracetam). Based on the applicable population of the EMPiRE model, we evaluated 280 patients registered in the Wenzhou Epilepsy Follow-up Registry Database from January 1, 2010, to December 31, 2020. A total of 158 eligible patients were included in the validation cohort. We collected data on the baseline characteristics of patients, eight predictors of the EMPiRE model and outcome events. The outcome was the occurrence of tonic-clonic or non-tonic-clonic seizures at any time in pregnancy up to 6 weeks postpartum. We used the equation of the EMPiRE model to obtain the predicted probabilities of seizures. The predictive ability of the EMPiRE model was quantified by the C-statistic (scale 0-1, values > 0.5 show discrimination), GiViTI calibration test and decision curve analysis (DCA). RESULTS: Of 158 eligible patients, 96 patients (60.8%, 96/158) experienced one or more seizures at any time between pregnancy and 6 weeks postpartum. The EMPiRE model showed good discrimination with a C-statistic of 0.76 (95% confidence interval [CI] 0.70-0.84). The GiViTI calibration belt showed that the predicted probabilities, which ranged from 16 to 96% (95% CI), were lower than the actual probabilities. DCA indicated that the highest net proportional benefit was obtained for predicted probability thresholds of 15-18% and 54-96%. CONCLUSIONS: The EMPiRE model could discriminate well between WWE with and without seizures during pregnancy and 6 weeks postpartum, but the risk of seizures may be underestimated. The limitations of the model for specific medication regimens may limit its real-world application. If the model is further improved, it will be incredibly valuable.

External validation and comparison of clinical scores for predicting late seizures after intracerebral hemorrhage in Chinese patients.

PURPOSE: Clinical scores have been established to predict the probability of late seizures following intracerebral hemorrhage (ICH) for individual patients, including the CAVE, CAVS and LANE scores. The purpose of this study was to compare these prediction scores in the Chinese population and undertake an independent external validation on them. METHODS: At one tertiary hospital in China, we retrospectively recruited consecutive inpatients who had been diagnosed with ICH. Medical records and tele interviews with a modified standardized questionnaire were used to identify late seizures. All the predictors of the prediction scores were collected from patient charts and databases by a standardized data collection protocol. The external validation of the prediction scores was quantified by the area under the curve (AUC), sensitivity, specificity, Youden index (YI), positive predictive value (PPV), and negative predictive value (NPV). RESULTS: 69 (5.4%) of 1276 patients experienced late seizures after ICH. There was no significant difference in the CAVE, CAVS, and LANE scores, which had AUCs of 0.75 (95% CI = 0.70-0.81), 0.74 (95% CI = 0.68-0.80), and 0.76 (95% CI = 0.70-0.82), respectively. At the optimal cutoff score, the LANE score had a lower sensitivity but a higher specificity than the CAVE and CAVS scores. Among the three prediction scores, the LANE score had a higher PPV than the others (0.145 vs. 0.088, 0.083), while the NPV was similar among the three prediction scores (0.989, 0.989, and 0.972). CONCLUSION: Our study showed that the CAVE, CAVS and LANE scores had similar AUCs for the occurrence of late seizures, but the LANE score had a relatively high PPV at the optimal cutoff score. Due to low evidence for using prophylactic antiseizure medications (ASM) in patients with ICH and poor availability of specialist stroke care in China, the LANE score with a cutoff score of 3 could be an applicable prediction tool in Chinese patients with ICH.

Structure-engineering the stability, electronic, optical and photocatalytic properties of hexagonal C2P2 monolayers.

Structure engineering presents unique opportunities in materials science field, including material design and modification. Herein, we applied structure engineering to double-sublayer hexagonal C2P2 monolayers so as to form two novel non-Janus structures and two new Janus structures. Based on first-principles calculations, the stability, electronic, optical, and photocatalytic properties of the C2P2 monolayers, including the two discovered structures and four new C2P2 monolayers, have been investigated. The results showed that these C2P2 monolayers are highly stable in energetics, dynamics, and thermodynamics. We also found that counterrotating 60° between the top and bottom sublayers could make the C2P2 monolayers become more stable. The calculations of the project band structures indicated that the new C2P2 monolayers were semiconductors with indirect band gaps ranging from 1.02 eV to 2.62 eV. Meanwhile, it was also suggested that the distributions of VBM and CBM in the two Janus C2P2 monolayers were out-of-plane due to their internal electric fields. Moreover, the carrier mobility of the C2P2 monolayers was anisotropic between an armchair and zigzag direction and quite high (reaching 103 cm2 V-1 s-1) in the zigzag direction. Additionally, all the C2P2 monolayers had large exciton binding energies (∼1.0 eV) and considerable absorption in the visible-light region. Furthermore, except for the CP-3 monolayer, all the C2P2 monolayers, including CP-1, CP-2, CP-4, CP-5, and CP-6, have great potential for metal-free visible-light photocatalytic water splitting. Our calculations reveal that structure engineering is particularly applicable to multi-sublayer two-dimensional materials for discovering new members and tuning their properties.

Two-dimensional H- and F-BX (X = O, S, Se, and Te) photocatalysts with ultrawide bandgap and enhanced photocatalytic performance for water splitting.

We theoretically propose a type of monolayer structure, H- or F-BX (X = As, Sb; Y = P, As), produced by surface hydrogenation or fluorination, with high stability, large band structures and high light absorption for photocatalytic water splitting. Based on first-principles calculations with the HSE06 functional, the electronic properties and optical properties were explored to reveal their potential performance in semiconductor devices. Additionally, owing to the Janus structure and high electronegativity of the monolayers, our calculations showed that surface fluorination can easily create an internal electric field compared with surface hydrogenation, which results in different trends of increasing bandgaps in monolayer H- and F-BX. We also found that the monolayers H- and F-BX have suitable band edges and high solar to hydrogen (STH) efficiency, enabling them to be photocatalysts for water splitting. Our work not only proposes eight monolayer semiconductors for expanding the number of two-dimensional semiconductors, but also provides a guide for how to regulate semiconductors for application in photocatalytic water splitting by using surface hydrogenation and fluorination.

Development and validation of a novel radiomics-clinical model for predicting post-stroke epilepsy after first-ever intracerebral haemorrhage.

OBJECTIVES: Post-stroke epilepsy (PSE) is associated with increased morbidity and mortality. This study aimed to develop and validate a novel prediction model combining clinical factors and radiomics features to accurately identify patients at high risk of developing PSE after intracerebral haemorrhage (ICH). METHODS: Researchers performed a retrospective medical chart review to extract derivation and validation cohorts of patients with first-ever ICH that attended two tertiary hospitals in China between 2010 and 2020. Clinical data were extracted from electronic medical records and supplemented by tele-interview. Predictive clinical variables were selected by multivariable logistic regression to build the clinical model. Predictive radiomics features were identified, and a Rad-score was calculated according to the coefficient of the selected feature. Both clinical variables and radiomic features were combined to build the radiomics-clinical model. Performances of the clinical, Rad-score, and combined models were compared. RESULTS: A total of 1571 patients were included in the analysis. Cortical involvement, early seizures within 7 days of ICH, NIHSS score, and ICH volume were included in the clinical model. Rad-score, instead of ICH volume, was included in the combined model. The combined model exhibited better discrimination ability and achieved an overall better benefit against threshold probability than the clinical model in the decision curve analysis (DCA). CONCLUSIONS: The combined radiomics-clinical model was better able to predict ICH-associated PSE compared to the clinical model. This can help clinicians better predict an individual patient's risk of PSE following a first-ever ICH and facilitate earlier PSE diagnosis and treatment. KEY POINTS: • Radiomics has not been used in predicting the risk of developing PSE. • Higher Rad-scores were associated with higher risk of developing PSE. • The combined model showed better performance of PSE prediction ability.

Halogen Engineering To Realize Regulable Multipolar Axes, Nonlinear Optical Response, and Piezoelectricity in Plastic Ferroelectrics.

Compared with uniaxial molecular ferroelectrics, multiaxial ferroelectrics have better application prospects because they are no longer subject to the single-crystal form and have been pursued in recent years. Halogen engineering refers to the adjustment of halogens in materials at the atomic level, which can not only explore multiaxial ferroelectrics but also help to improve piezoelectrics, recently. In this work, we successfully synthesized and characterized three multiaxial plastic ferroelectrics through the precise molecular design from I to Cl, confirming the increase of the number of polar axes of ferroelectrics from 3 to 6, the increase of second-harmonic generation density from 2.1 times to nearly 6 times of monopotassium phosphate, and the increase of piezoelectric coefficient by 140%. This systematic work has proved that halogen engineering can not only enrich the family of multiaxial plastic ferroelectrics but also promote the further development of nonlinear optical and piezoelectric materials.

Two dimensional twin T-graphene: monolayer for visible-light photocatalytic water splitting and bulk for anode material of magnesium batteries.

Two-dimensional (2D) carbon allotropes with all-sp2-hybridization have demonstrated great potential in nano-photoelectric devices, but the application of semiconductor photocatalysts for water splitting and anodes in magnesium batteries remains unoptimistic. Motivated by this, we theoretically study a highly stable all-sp2-hybridized 2D carbon allotrope twin T-graphene (TTG) via first-principles simulations. And through the calculations of the HSE06 functional, we find that TTG has a wide bandgap (2.70 eV) and suitable band edge positions satisfying the criteria of photocatalysts for overall water splitting. Additionally, TTG exhibits excellent photocatalytic properties for overall water splitting reflecting a high STH efficiency (12.34%), strong absorption coefficient in the visible-light region and the carrier mobility being high for electrons but low for holes. By investigating the strain effects, we get that, with biaxial compressive strain, the ability of overall photocatalytic water splitting can be effectively improved including STH up to ∼30%. Moreover, the bulk TTG also exhibits great potential as an anode material of magnesium batteries with a theoretical capacity of 556 mA h g-1, average voltage of 0.74 V and diffusion energy barrier of ∼0.96 eV. Our results would broaden the application of all-sp2-hybridized 2D carbon allotropes in the semiconductor photocatalytic and magnesium batteries field.

Association between minimally invasive surgery and late seizures in patients with intracerebral hemorrhage: A propensity score matching study.

Purpose: The association between minimally invasive surgery (MIS) for hematoma evacuation and late seizures after intracerebral hemorrhage (ICH) remains uncertain. We aimed to investigate whether MIS increases the risk of late seizures after ICH and identify the risk factors for late seizures in this patient subgroup. Methods: We retrospectively included consecutive inpatients diagnosed with ICH at two tertiary hospitals in China. The subjects were divided into the MIS group (ICH patients who received MIS including hematoma aspiration and thrombolysis) and conservative treatment group (ICH patients who received conservative medication). Propensity score matching was performed to balance possible risk factors for late seizures between the MIS and conservative treatment groups. Before and after matching, between-group comparisons of the incidence of late seizures were performed between the MIS and conservative treatment groups. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for late seizures in MIS-treated patients. Results: A total of 241 and 1,689 patients were eligible for the MIS and conservative treatment groups, respectively. After matching, 161 ICH patients from the MIS group were successfully matched with 161 ICH patients from the conservative treatment group (1:1). Significant differences (p < 0.001) were found between the MIS group (31/241, 12.9%) and conservative treatment group (69/1689, 4.1%) in the incidence of late seizures before matching. However, after matching, no significant differences (p = 0.854) were found between the MIS group (17/161, 10.6%) and conservative treatment group (16/161, 9.9%). Multivariate logistic regression analysis revealed that cortical involvement (OR = 2.547; 95% CI = 1.137-5.705; p value = 0.023) and higher National Institutes of Health Stroke Scale (NIHSS) scores (OR = 1.050; 95% CI = 1.008-1.094; p value = 0.019) were independent risk factors for late seizures. Conclusion: Our study revealed that receiving MIS did not increase the incidence of late seizures after ICH. Additionally, cortical involvement and NIHSS scores were independent risk factors for late seizures in MIS-treated patients.

Exploring the photocatalytic properties and carrier dynamics of 2D Janus XMMX' (X = S, Se; M = Ga, In; and X' = Te) materials.

Recently, two-dimensional (2D) Janus structures have been extensively explored because of their robust electron mobility and unique photocatalytic properties. In spite of the increasing interest, the origin of high photocatalytic activities and the behaviors of photoinduced carriers in this kind of materials have not been well understood. Herein, we present a step-by-step protocol based on the first-principles calculations combined with the ab initio non-adiabatic molecular dynamics (NAMD) simulations to unveil the origin of high photocatalytic activity of highly stable typical 2D Janus XMMX' structures (X = S, Se; M = Ga, In; and X' = Te). Their band structures, optical properties, exciton binding energies, carrier effective masses, solar-to-hydrogen efficiency, hot carrier relaxation and recombination times, etc. have been calculated. We find that the difference between X and X' atoms on the two surfaces of the XMMX' monolayer not only builds an out-of-plane electric field, which significantly affects the charge distributions on the valence band maxima (VBM) and the conduction band minima (CBM) and subsequently decreases the exciton binding energy, but also transforms the indirect band structures of XM into the direct ones with well suitable energy gaps for visible-light absorption as well as endows the XMMX' structures with unequal electron and hole mobility, rapid hot carrier relaxation and slow electron-hole recombination processes on a timescale of tens of nanoseconds. The current work suggests that Janus XMMX' monolayers are good photocatalytic materials for overall water splitting and provides a guide to regulate the materials' properties for efficient energy harvesting and optoelectronic applications.

Superior mechanical flexibility, lattice thermal conductivity and electron mobility of the hexagonal honeycomb carbon nitride monolayer.

Nitrogen is the nearest neighbor element of carbon and, thus, the hexagonal honeycomb carbon nitride monolayer (CxNy), which consists of a covalent network of carbon and nitrogen atoms, usually has attractive physical and chemical properties similar to those in graphene. Here, we systematically investigate the geometric structure, mechanical properties, thermal transport properties, and plasmon excitation of a new phase, labeled C3N2, and make a detailed comparison with other possible CxNy allotropes. All CxNy have a super-high layer modulus and Young's modulus. But compared with the others, C3N2 exhibits excellent mechanical flexibility, and can withstand a relatively high critical strain up to 20% (18%) along the X(Y) direction. Additionally, C3N2 also has excellent thermal and electronic transport properties, with a super-high lattice thermal conductivity of ∼110.9 W m-1 K-1 and electron mobility of ∼1617.52 cm2 V-1 s-1 at 300 K. By performing time-dependent density functional theory (TDDFT), we obtain the optical absorptions of C3N2 and C3N, and meanwhile analyze their Fourier transforms of induced charge densities at some resonant frequencies. The main optical absorption peaks of the C3N2 nanostructure are located in the ultraviolet region, and its plasmon peaks are far higher than those in C3N. Its excellent mechanical and optical properties, the larger electronic band gap, and the higher electron mobility suggest that C3N2 has great potential for application in nanoelectronics and optoelectronics.

The impact of social factors, especially psychological worries on anxiety and depression in patients with epilepsy.

BACKGROUND: Social factors are believed to affect mental health in patients with epilepsy (PWE). However, there is still a lack of sufficient manifest proof, given the difficulty of exposing PWE to relatively consistent natural social environments with a low or high level of social interaction to study their significant role. METHODS: This single-center, longitudinal study was conducted via online questionnaires during the coronavirus disease 2019. PWE were recruited from downtown Wuhan and surrounding areas. The Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 were used to assess psychological status. RESULTS: We analyzed 588 questionnaires completed by 294 PWE who participated in the dual survey. Under lockdown and reopening, the prevalence of anxiety was 13.6%/22.5%, and the prevalence of depression was 19.4%/34.0%. Raising children and seizure-related characteristics, including uncontrolled seizures, seizure exacerbation, seizure frequency ≥ 2/m, and changes in drug regimen, were risk factors in the first and second surveys. A high education level (OR = 1.946, 95% CI = 1.191-3.182), low life satisfaction (OR = 1.940, 95% CI = 1.007-3.737), worry about unanticipated seizures (OR = 2.147, 95% CI = 1.049-4.309), and worry about purchasing medication outside (OR = 2.063, 95% CI = 1.060-4.016) were risk factors for higher scores after reopening. Worry about unanticipated seizures (OR = 3.012, 95% CI = 1.302-6.965) and in-person medical consultation (OR = 2.319, 95% CI = 1.262-4.261) were related to newly diagnosed patients with psychological disorder after reopening. CONCLUSIONS: We identified an association between social variables and epileptic psychiatric comorbidities.

Predicting the occurrence of early seizures after cerebral venous thrombosis using a comprehensive nomogram.

BACKGROUND: Seizure is a common clinical manifestation of cerebral venous thrombosis (CVT). The mortality rate of patients with CVT with seizure is three times higher than that of patients without seizure. The aim of this study was to develop a nomogram to predict the individual probability of acute seizure events in patients with CVT. METHOD: This was a single-center, retrospective cohort study. We analyzed and compared demographic variables, epidemiological risk factors, clinical presentation, laboratory results and imaging data in a cohort of 142 patients who were diagnosed with CVT in our hospital from January 2013 to December 2018. A nomogram was constructed to predict the risk of early seizure (ES) in these patients according to the multivariable logistic regression analysis results. The concordance index, GiViTi calibration belt and decision curve analysis (DCA) were used to assess nomogram performance. RESULTS: Forty-three (30.28%) patients experienced seizure within 2 weeks after a CVT diagnosis. Multivariate analysis identified focal neurologic deficit, Glasgow Coma Scale (GCS) scores ≤ 8 on admission, hemorrhagic lesions, superior sagittal sinus thrombosis (SSST) and frontal lobe lesions as independent predictive factors for ES occurrence after CVT. A nomogram was generated based on these predictive factors with the concordance index reaching 0.82, indicating that the clinical tool was well calibrated. DCA showed that the model was useful with a threshold probability in the range of 0-77%. CONCLUSIONS: We developed the first nomogram that could predict the risk of ES in CVT patients. This effective and convenient tool has shown promising clinical benefit and will assist clinicians in making treatment decisions.

Agmatine Alleviates Epileptic Seizures and Hippocampal Neuronal Damage by Inhibiting Gasdermin D-Mediated Pyroptosis.

Background: Epilepsy is a common neurological disease, and neuroinflammation is one of the main contributors to epileptogenesis. Pyroptosis is a type of pro-inflammatory cell death that is related to epilepsy. Agmatine, has anti-inflammatory properties and exerts neuroprotective effects against seizures. Our study investigated the effect of agmatine on the core pyroptosis protein GSDMD in the context of epilepsy. Methods: A chronic epilepsy model and BV2 microglial cellular inflammation model were established by pentylenetetrazole (PTZ)-induced kindling or lipopolysaccharide (LPS) stimulation. H&E and Nissl staining were used to evaluate hippocampal neuronal damage. The expression of pyroptosis and inflammasome factors was examined by western blotting, quantitative real-time PCR, immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Results: Agmatine disrupted the kindling acquisition process, which decreased seizure scores and the incidence of full kindling and blocked hippocampal neuronal damage. In addition, agmatine increased BV2 microglial cell survival in vitro and alleviated seizures in vivo by suppressing the levels of PTZ-induced pyroptosis. Finally, the expression of TLR4, MYD88, phospho-IκBα, phospho-NF-κB and the NLRP3 inflammasome was significantly upregulated in LPS-induced BV2 microglial cells, while agmatine suppressed the expression of these proteins. Conclusions: Our results indicate that agmatine affects epileptogenesis and exerts neuroprotective effects by inhibiting neuroinflammation, GSDMD activation, and pyroptosis. The inhibitory effect of agmatine on pyroptosis was mediated by the suppression of the TLR4/MYD88/NF-κB/NLRP3 inflammasome pathway. Therefore, agmatine may be a potential treatment option for epilepsy.

Renin-angiotensin system inhibition reverses the altered triacylglycerol metabolic network in diabetic kidney disease.

OBJECTIVE: Dyslipidemia is a significant risk factor for progression of diabetic kidney disease (DKD). Determining the changes in individual lipids and lipid networks across a spectrum of DKD severity may identify lipids that are pathogenic to DKD progression. METHODS: We performed untargeted lipidomic analysis of kidney cortex tissue from diabetic db/db and db/db eNOS-/- mice along with non-diabetic littermate controls. A subset of mice were treated with the renin-angiotensin system (RAS) inhibitors, lisinopril and losartan, which improves the DKD phenotype in the db/db eNOS-/- mouse model. RESULTS: Of the three independent variables in this study, diabetes had the largest impact on overall lipid levels in the kidney cortex, while eNOS expression and RAS inhibition had smaller impacts on kidney lipid levels. Kidney lipid network architecture, particularly of networks involving glycerolipids such as triacylglycerols, was substantially disrupted by worsening kidney disease in the db/db eNOS-/- mice compared to the db/db mice, a feature that was reversed with RAS inhibition. This was associated with decreased expression of the stearoyl-CoA desaturases, Scd1 and Scd2, with RAS inhibition. CONCLUSIONS: In addition to the known salutary effect of RAS inhibition on DKD progression, our results suggest a previously unrecognized role for RAS inhibition on the kidney triacylglycerol lipid metabolic network.