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Abstract Objective Diabetic kidney disease (DKD) is characterized by the abnormal deposition of oxidized low-density lipoprotein (ox-LDL), which contributes to podocyte damage. Klotho, an aging suppressor that plays a critical role in protecting podocytes in DKD, is mainly expressed in kidney tubular epithelium and secreted in the blood. However, it has not been established whether Klotho can alleviate podocyte injury by inhibiting renal ox-LDL deposition, and the potential molecular mechanisms require further investigation. Methods We conducted a comprehensive analysis of serum and kidney biopsy samples obtained from patients diagnosed with DKD. Additionally, to explore the underlying mechanism of Klotho in the deposition of ox-LDL in the kidneys, we employed a mouse model of DKD with the Klotho genotype induced by streptozotocin (STZ). Furthermore, we conducted meticulous in vitro experiments on podocytes to gain further insights into the specific role of Klotho in the deposition of ox-LDL within the kidney. Results Our groundbreaking study unveiled the remarkable ability of the soluble form of Klotho to effectively inhibit high glucose-induced ox-LDL deposition in podocytes affected by DKD. Subsequent investigations elucidated that Klotho achieved this inhibition by reducing the expression of the insulin/insulin-like growth factor 1 receptor (IGF-1R), consequently leading to a decrease in the expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) and an enhancement of mitochondrial function. Ultimately, this series of events culminated in a significant reduction in the expression of the oxidized low-density lipoprotein receptor (OLR1), thereby resulting in a notable decrease in renal ox-LDL deposition in DKD. Conclusion Our findings suggested that Klotho had the potential to mitigate podocyte injury and reduced high glucose-induced ox-LDL deposition in glomerulus by modulating the IGF-1R/RAC1/OLR1 signaling. These results provided valuable insights that could inform the development of novel strategies for diagnosing and treating DKD. Graphical Abstract

Abstract Background Proteinuria is an unfavorable clinical condition highly associated with a risk of renal and cardiovascular disease in chronic kidney disease (CKD). However, whether all proteinuria forms are linked to renal impairment are still unclear. Cubilin is an endocytic receptor highly expressed in renal proximal tubules mediating uptake of albumin, transferrin and α1-microglobulin. Methods Exome sequencing method initially identified candidate genes. With the application of exome sequencing combined with Sanger sequencing, we further focused on CUBN through bioinformatics analysis. The pathogenic effects of the potentially causative variants were verified utilizing complementary analysis of clinical data and systematic characterization of the variants’ expression and function with clinical samples and in vitro experiments in HEK293T cell lines along with in vivo experiments in mice. Results In this study, we identified four novel variants locating after the vitamin B12 (vitB12)-binding domain of Cubilin (encoded by CUBN, NM_001081.3: c.4397G > A (p.C1466Y), c.6796C > T (p.R2266X), c.6821 + 3A > G and c.5153_5154delCT (p.S1718X)) in two families. Moreover, the variants severely affected the expression and function of Cubilin in renal proximal tubules and caused albuminuria, increasing levels in urine transferrin and α1-microglobulin, but without progressive glomerular filtration barrier (GFB) impairment, vitB12 deficiencies or abnormal blood levels of HDL and albumin. Further mechanistic insights showed that the variants after the vitB12-binding domain of CUBN merely disrupted the association with Amnionless (AMN) that exhibited aberrant localization in cell cytoplasm rather than membrane. Conclusions Here, our findings suggested that different mutation types after the vitB12-binding domain of CUBN uncouple proteinuria from glomerular filtration barrier, that may be an unexpectedly common benign condition in humans and may not require any proteinuria-lowering treatment or renal biopsy.

Background and Aims: Sessile serrated lesions (SSLs) develop colorectal cancer (CRC), through a critical intermediary stage of SSL with dysplasia (SSLd). In this prospective observational study, we aimed to assess clinicopathological correlates of SSLd in the setting of a high lesion-detection rate. Methods: Patients diagnosed with SSL and SSLd from February 2018 until January 2020 were prospectively recruited, and SSLd specimens were re-evaluated by 2 expert pathologists in a blinded manner. Associations were analyzed using multivariate logistic regression models. Results: A total of 6425 patients underwent 7423 colonoscopies, and 2671 SSLs were resected from 1047 patients. The overall SSL detection rate per colonoscopy was 15.9%. The median age of patients with SSL was 54 years (interquartile range, 39–66), and 43.3% were male. After pathologist review, 24 SSLds were confirmed in 20 patients. The median size of SSLd was 8 mm (interquartile range, 5.75–15.25), and 13 of 24 SSLds were

Abstract Background Hereditary tyrosinemia type 1 (HT1) is a rare inherited metabolic disease characterized by severe liver and renal dysfunction. Early identification in affected children is critical for improved treatment options and prognosis. Methods In this study, we identified novel compound heterozygous mutations (NM_000137: c.657delC (p.K220Rfs*12) and c.607G>A (p.A203T)) in the fumarylacetoacetate hydrolase (FAH) gene in a family. We also characterized the clinical phenotype of the proband and verified the pathogenic effects of the mutations. Furthermore, we explored the pathogenic mechanism of renal injury through renal biopsy pathology and cell‐based in vitro assays. Our study aims to verify the association between novel fumarylacetoacetate hydrolase (FAH) variants and HT1, confirm the pathogenic effects of the mutations and explore the pathogenic mechanism of renal injury. Results We showed these FAH mutations were inherited in an autosomal recessive manner and resulted in abnormal FAH protein expression and dysfunction, leading to fumarylacetoacetate (FAA) accumulation. The proband also showed apparent renal injury, including glomerular filtration barrier dysfunction and abnormal tubular protein reabsorption. Conclusions These observations may provide deeper insights on disease pathogenesis and identify potential therapeutic approaches for HT1 from a genetic perspective. Similarly, we hope to provide valuable information for genetic counseling and prenatal diagnostics.

Abstract Direct‐drive permanent magnet synchronous generators (DDPMSGs) are gaining more and more attention in the field of wind power because of the advantages of simple structure, high efficiency and high reliability. However, due to the extremely low rotational speed, large volume and heavy weight of DDPMSGs, it poses serious challenges for transportation and installation, which limits its application. Therefore, a DDPMSG with novel toroidal windings (NTW) is proposed to improve power density in this paper. Unlike regular windings, each coil of the NTWs is wound onto the stator yoke in the same direction. The special configuration enables the generator to have higher winding coefficient, so that the DDPMSG with NTWs (NTW‐DDPMSG) can achieve higher power density than traditional fractional slot concentrated windings (FCW). The proposed topology and operating principles are described in detail. To verify the merits of the proposed NTW‐DDPMSG, the electromagnetic parameters of two external rotor surface‐mounted DDPMSGs equipped with NTW and FCW respectively are designed. The characteristics of air‐gap magnetic field, no‐load electromotive force, output power, loss and efficiency are analysed on the conditions of different loads and speeds. Comparison results show that the proposed NTW‐DDPMSG has higher power density than FCW‐DDPMSG.

To lower the difficulty of fault protection, a doubly-fed induction machine based shipboard propulsion system (DFIM-SPS) that is partially power decoupled is presented. In such an intrinsically safe SPS architecture, a synchronous generator (SG) is employed for power generation, and the accuracy of the parameters of power generation unit (PGU) plays an important role in SPS stable operation. In this paper, the PGU parameter deviations are studied to evaluate the effects on system performance. The models of salient-pole SG, type DC1A excitation system (EXS) and DFIM are illustrated first. Besides, the corresponding control scheme is explained. For the 16 important parameters of PGU, up to 40% of parameter deviations are applied to implement parameter sensitivity analysis. Then, simulation studies are carried out to evaluate the parameter deviation effects on system performance in detail. By defining three parameter deviation effect indicators (PDEIs), the effects on the PGU output variables, which are the terminal voltage and output active power, are studied. Moreover, the increasing rates of PDEIs with different degrees of parameter deviations for the key parameters are analyzed. Furthermore, the overall system performance is investigated for the two most influential PGU parameters. This paper provides some vital clues on SG and EXS parameter identification for DFIM-SPS.

This paper presents a technical overview for fault diagnosis and fault-tolerant strategies of switched reluctance machine (SRM) systems. With the widespread utilization of electrical motors, stability and reliability become the most important considerations for safety. SRMs are famous for their great robustness, wide speed range, and high fault-tolerant capability, which are much suitable for high-speed and safety-critical applications. Although the SRM drive have some fault tolerance ability, the fault still seriously affects the system performance. The faults happening in different parts, such as converter, motor winding, sensors, and rotor, may lead to low torque, large torque ripple, overcurrent, insulation damage, and even system broken-down, without any fault-tolerant consideration. Therefore, it is important and urgent to improve the motor system reliability and robustness for SRM drives. Aiming at offering novel solutions to the faults in SRM drives, this paper begins with mathematical modeling of the SRM, and then concentrates on the state-of-art fault diagnosis and fault tolerance techniques to enhance the fault ride-through ability. Two categories, containing fault diagnosis and fault tolerance technologies are emphasized for fast faults locating and stable post-fault operation. Advanced technologies are reviewed, classified, and compared comprehensively. Besides, several fault diagnosis and tolerance schemes that have been developed by authors are presented and discussed as well. Finally, the research status and outlooks on this topic are put forward. It is our target to offer a global vision on fault-related strategies and bring out promising ideas about fault-related techniques in SRM drives.

This paper investigates the optimal design method of switched reluctance machines (SRMs) for mitigating torque ripple and improving average torque under the low speed operation. In order to produce high torque for hill climbing or overload start-up of micro electric vehicles (EVs) and reduce the converter capacity, an SRM with four times torque overload capability and two times speed range with constant power is needed. To improve the SRM performance, first, a new method called multiphase excitation (MPE) method for calculating resultant static torque is adopted, which takes the cross-coupling and magnetic saturation into consideration to reduce the calculation error bought by the traditional method called single-phase excitation (SPE) method; second, optimal methods, including parameters sensitivity analysis, multi-objective optimization function, and winding connection types, have been taken to release the magnetic saturation, to improve average torque, and to depress torque ripple. Compared with the initial scheme, the torque ripple is minimized from 55.33% to 14.84% and the average torque is improved by 8.36%. The experimental results validate the effectiveness of the proposed methods.

As winding short-circuit faults (WSF) in a direct-drive permanent magnet synchronous motor (DDPMSM) degrade its reliability and may cause serious catastrophes, fault detection and diagnosis for the DDPMSM are necessary. The performances analyses of motor under WSF are the basis of fault detection and diagnosis. An efficient and accurate faulty model is a great tool for evaluating motor performances under various WSF. Hence, this paper proposes a novel physical faulty model (PFM) based on the coil sub-element for the DDPMSM with the WSF. Fault position can be examined by differentiating the inductance and the electromotive force of the coil sub-element. This model can evaluate motor performances under various WSF, especially inter-turn short-circuit fault in different positions of the same slot, without changing the internal structure of model. The faults are set by connecting the desired taps as in the practical motor. First, the structure and parameters of the DDPMSM are reported. Second, the inductance calculation matrix, which considers the spatial position of the fault, is constructed. Then, the proposed PFM is established. The motor performances under various WSF are evaluated. Finally, the results of PFM, finite element model and experiment are compared. The results validate the correctness of the proposed PFM.

Double-stator switched reluctance motors (DSSRMs) are gaining much attention due to advantages of higher power/torque density and lower acoustic noise compared to conventional SRMs. In this paper, a novel three-phase 12/8/12-pole DSSRM design method is proposed by multiple pole arcs optimization for higher torque and lower torque ripple applications. A constrained quadrilateral is first presented to restrict the combinations of pole arcs according to motor operation conditions. Then, multiple parametric analysis processes are employed to analyze the effects of pole arcs on static torque in 3-D finite-element modeling environment. In order to select the optimal combinations of pole arcs generating higher torque, an effective torque evaluation principle is presented. Instead of the conventional 22.5° rotor position range, 15° range is adopted to calculate the average torque according to the static torque profiles, which is more effective to evaluate the torque capability. The selected torque range considers not only the excitation and demagnetization processes of phase currents but also the optimal range for torque generation. Finally, in order to achieve a lower torque ripple, the transient simulation is further carried out to identify the optimal pole arcs by comparing the torque ripple, average torque, and efficiency.

This paper presents a new topology of switched reluctance motor (SRM) drives for plug-in hybrid electric vehicles. Six operating modes can be achieved as a result. Three of those modes are applied for driving and the others for charging. During the driving mode, the topology can be converted to a fourlevel one. During the charging mode, two battery packs are charged in parallel with the boost circuit by the external ac source or generators. The main contributions of the proposed topology are as follows. First, a four-level converter is formed by adopting different ways of connection (series or parallel) of the two battery packs (or the two capacitors), which can accelerate the excitation and demagnetization procedures of SRMs. Moreover, the topology contributes to decreasing the switching losses and extending the constant torque region to improve the drive performance as well. Second, the state of charge of the two battery packs (or the voltages of two capacitors) can keep balance on their own by parallel operation of the two battery packs. Furthermore, a detailed comparison between two drive modes of the proposed topology and asymmetric half bridge inverters is undertaken with simulation and experimental studies, the results of which demonstrate the validity of the proposed topology.

This paper proposes an efficiency optimization method for the permanent magnet synchronous motor (PMSM) based powertrain by using field-circuit coupled finite-element method (FEM) for electric vehicle or hybrid electric vehicle applications. In this paper, an alterable flux-weakening (FW) angle is employed in the armature current control strategy for the FW operation. The optimal FW angle for each certain operating condition can be obtained through the pre-selection, which improves the system efficiency compared to conventional FW methods. Then, the lookup table (LUT) for optimal armature current control commands is obtained. Through using this optimal LUT in the drive system, the system efficiency can be significantly improved for the entire operation range. The time-stepping FEM is used to simulate the PMSM system, which integrates the electromagnetic field analysis of the motor prototype and the control algorithm of the drive system. A 2-D transient FEM model is built for a 15 kW PMSM in ANSYS Maxwell, and a vector control circuit model is set up in ANSYS Simplorer. Experiments are carried out on the 15 kW PMSM prototype to verify the accuracy of the simulation results and the effectiveness of the proposed design method.

This paper proposes a coordinated control of doubly fed induction generator (DFIG)-based wind farms' (WFs) post-fault active power and synchronous generators' (SGs) tripping with the aim of improving transient stability of both the first swing and multi swings. To achieve it, the impact mechanism of the WFs' post-fault active power and SGs' tripping on the stability margin of each swing is first presented by using extended equal area criterion (EEAC). Based on this, a principle of the coordinated control is put forward. The WFs' control period is designed as six stages, and the value of post-fault active power in each stage is suggested to improve the stability of the first five swings and maintain the post-fault steady state. To decrease the tripping amount of the SGs, the SGs are tripped only when WFs' control effect is not sufficient to avoid the instability. Then, by utilizing an “online pre-decision and real-time matching”scheme, an engineering application method for the control principle is proposed, where the control procedures and detailed parameters calculation are demonstrated. The numerical simulations show that the coordinated control has a better damping effect and a less control cost (less amount of tripped SGs) than the traditional DFIG control or traditional SG tripping.

This paper presents a technical overview for low-noise switched reluctance motor (SRM) drives in electric vehicle (EV) applications. With ever-increasing concerns over environmental and cost issues associated with permanent magnet machines, there is a technical trend to utilize SRMs in some mass production markets. The SRM is gaining much interest for EVs due to its rare-earth-free characteristic and excellent performance. In spite of many advantages compared with conventional adjustable-speed drives, SRMs suffer from torque ripple and radial distortion (and thus noise and vibration) by their nature. Therefore, for high-performance vehicle applications, it is important and urgent to optimize the SRM system to overcome the drawbacks of the noise and vibration. In order to present clear solutions to the acoustic noise in SRMs, this paper starts by analyzing the mechanism of the radial vibration and torque ripples inherent in the motors, and then focuses on the state-of-the-art technologies to mitigate the radial force and torque ripples. It highlights two categories for low-noise SRMs, including the machine topology improvement and control strategy design for radial vibration mitigation and torque ripple reduction. Advanced technologies are reviewed, classified, and compared accordingly. In addition to these methodologies, the schemes that have been developed by authors are also presented and discussed. Finally, the research status on this topic is summarized and forecast research hotspots are presented. It is our intention that this paper provides the guidance on performance improvements for low-noise SRM drives in EV applications.

Introduction Idiopathic nephrotic syndrome (INS) is the most common glomerulopathy that results in childhood chronic kidney disease in China, but the relationships between different clinical phenotypes and immunological genetic variants observed in patients with INS are ambiguous and have not been well studied. A cohort study combined with whole exome sequencing might further identify the effects of immunological genetic variants on clinical phenotypes and treatment outcomes.Methods and analysis We describe a 3 year prospective observational single-centre cohort study to be conducted in the Children’s Hospital of Chongqing Medical University in China. This study will recruit and investigate 336 patients with childhood-onset INS presenting with different clinical phenotypes. Whole exome sequencing will be conducted when patients progress to a confirmed clinical phenotype during follow-up. Relevant clinical and epidemiological data, as well as conventional specimens, will be collected at study entry and 1 month, 3 months, 6 months, 1 year, 2 years and 3 years after disease onset. After this cohort is generated, the immunological genetic variants of steroid-sensitive nephrotic syndrome without frequent relapse, steroid-resistant nephrotic syndrome and steroid-dependent/frequent relapse nephrotic syndrome will be evaluated.Ethics and dissemination The study protocol is approved by Ethics Committee of Children’s Hospital of Chongqing Medical University (reference number 2018–140). The results will be disseminated through peer-reviewed journals and conference presentations.Trial registration number ChiCTR1800019795

A tubular permanent-magnet linear generator is suitable for direct drive wave energy conversion owing to its simple structure, easy maintenance and high efficiency. In this study, a novel Gramme winding tubular permanent-magnet linear generator (GW) is designed to increase power density. First, the structure of the Gramme winding and concentrated winding tubular permanent-magnet linear generator is introduced and the operation principle of the generator is analysed. Second, the initial parameters of GW are determined based on the similar overall dimensions to those of the concentrated winding tubular permanent-magnet linear generator. Third, the air gap flux density, external characteristics, voltage regulation, output power, and loss of the two generators are compared. Finally, the DC load capacities of the two generators are compared based on a three-phase full-control bridge rectifying circuit. The results show that the GW has a higher power density than the latter.

A two-degree-of-freedom direct-drive induction motor (2DoFDDIM), whose solid rotor is coated with a copper layer, is capable of linear, rotary, and helical motions and has widespread applications. For solid-rotor motors, the calculation and analysis of rotor total eddy current loss (TECL) are crucial in studying the factors causing such a loss and possible loss reduction methods. In this study, a new nonlinear analytical method considering the saturation of the rotor core is proposed to solve the fundamental magnetic field. The new method divides the time period into segments. The magnetic field distribution at any time is obtained using Maxwell equations. The eddy current losses in the copper layer and rotor core caused by the fundamental magnetic field are calculated. The surface eddy current losses in the copper layer and rotor core caused by harmonics are calculated using a 2D analytical method. TECL is determined by the sum of eddy current and surface eddy current losses. Coefficients are utilized to consider eddy, saturation, and end-region effects when calculating the rotor core TECL. The new method is verified using 3D FEM, and the results show the proposed method has higher accuracy than the original method. The errors of the rotor core and copper layer TECLs are less than 6 % and 7.3 % , respectively.

A direct-drive motor has the merits of low speed, high torque, and elimination of mechanical deceleration mechanisms, and is widely used in various fields. A novel direct-drive permanent magnet synchronous motor is presented herein, in which all coils are wrapped around the stator yoke in the same orientation. The structure of the novel direct-drive permanent magnet synchronous motor with toroidal windings (N-TWDDPMSM) is introduced and its operating principle is analyzed by describing the variation in the armature magnet field versus time. Furthermore, based on the same power grade and mechanical size, several finite-element models of motors with different windings are established using Magnet software to analyze the distribution of magnetic field, back-electromotive force (back-EMF), power-angle characteristics, loss characteristics, etc. Compared with the traditional permanent magnet synchronous motor (T-PMSM), the traditional permanent magnet synchronous motor with toroidal windings (T-TWPMSM), and the N-TWDDPMSM, the N-TWDDPMSM shows advantages of low speed and high torque, and the feasibility and superiority of the N-TWDDPMSM are verified.

Internal defects inside power cable joints due to unqualified construction is the main issue of power cable failures, hence in this paper a method based on thermal probability density function to detect the internal defects of power cable joints is presented. First, the model to calculate the thermal distribution of power cable joints is set up and the thermal distribution is calculated. Then a thermal probability density (TPD)-based method that gives the statistics of isothermal points is presented. The TPD characteristics of normal power cable joints and those with internal defects, including insulation eccentricity and unqualified connection of conductors, are analyzed. The results indicate that TPD differs with the internal state of cable joints. Finally, experiments were conducted in which surface thermal distribution was measured by FLIR SC7000, and the corresponding TPDs are discussed.

Renewable energy and electric vehicles have become involved in power systems, which has attracted researchers to stochastic continuous disturbances (SDEs). This paper addresses stochastic analysis issues for the stability of a power system with losses under SDEs. Firstly, the quasi-Hamiltonian models of power systems with losses under SDEs are given. Secondly, a novel analytical method is proposed to analyze the stability of the power system with losses under SDEs based on the stochastic averaging method. Thirdly, comparisons of stability probability under different parameters are performed, from which insights to improve the stability probability of power systems with losses under SDEs can be obtained. Even though it is challenging to assess the stability of a power system with losses under SDEs, the proposed method in this paper could serve well in this regard.

In this paper, a multifunctional isolated and non-isolated dual-mode low-power converter was designed for renewable energy conversion applications such as photovoltaic power generation to achieve different operating modes under bi-directional electrical conversion. The proposed topology consists of a bidirectional non-isolated DC/DC circuit and an isolated converter with a high-frequency transformer, which merge the advantages of both the conventional isolated converter and non-isolated converter with the combination of the two converter technologies. Compared with traditional converters, the multifunctional converter can not only realize conventional bi-directional functions, but can also be applied for many different operation modes and meet the high output/input ratio demands with the two converter circuits operating together. A novel control algorithm was proposed to achieve the various functions of the proposed converter. An experimental platform based on the proposed circuit was established. Both the simulation and experimental results indicated that the proposed converter could provide isolated and non-isolated modes in different applications, which could meet different practical engineering requirements.

This paper investigates the performance of a fault-tolerant four-switch three-phase (FSTP) grid-side converter (GSC) in a doubly-fed induction generator-based wind turbine (DFIG-WT). The space vector pulse width modulation (SVPWM) technique is simplified and unified duty ratios are used for controlling the FSTP GSC. Steady DC-bus voltage, sinusoidal three-phase grid currents and unity power factor are obtained. In addition, the balance of capacitor voltages is accomplished based on the analysis of current flows at the midpoint of DC bus in different operational modes. Besides, external disturbances such as fluctuating wind speed and grid voltage sag are considered to test its fault-tolerant ability. Furthermore, the effects of fluctuating wind speed on the performance of DFIG-WT system are explained according to an approximate expression of the turbine torque. The performance of the proposed FSTP GSC is simulated in Matlab/Simulink 2016a based on a detailed 1.5 MW DFIG-WT Simulink model. Experiments are carried out on a 2 kW platform by using a discrete signal processor (DSP) TMS320F28335 controller to validate the reliability of DFIG-WT for the cases with step change of the stator active power and grid voltage sag, respectively.