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Abstract Aiming at the problem of sub‐synchronous oscillations induced by direct‐drive wind farms with series‐compensated lines, this paper proposes an unknown system dynamics estimation‐based PI controller to achieve sub‐synchronous oscillation suppression. According to the mathematical model of the direct‐drive wind farm grid‐connected system, the relationship between the direct‐drive wind turbine grid‐side converter current inner‐loop PI controller and the sub‐synchronous components is first established. Secondly, the uncertain sub‐synchronous current components and voltage components in the series‐compensated lines of the direct‐drive wind farm are taken as the total disturbance, and an unknown system dynamic estimator‐based PI controller is designed by introducing the first‐order low‐pass filter operation. Then, the stability and convergence of the closed‐loop system are proved by Lyapunov theory. Finally, the Prony method is used to analyse the current signal output by the direct‐drive wind turbine, and the inherent characteristics of the negative damping of the SSO induced by the series‐compensated line of the direct‐driven wind farm are revealed. A comparative numerical simulation is carried out to demonstrate that the sub‐synchronous oscillations of the direct‐drive wind farm with series‐compensated lines can be suppressed under different operating conditions.

Abstract To solve the problem of oscillation instability in permanent magnetic synchronous generator (PMSG)-based wind power connected systems during low-voltage ride through (LVRT) process, a parameter adjustment strategy based on interaction energy path optimization is proposed in this paper. Firstly, a modular state-space model of PMSG under fault transient conditions is constructed, and the system is divided into five subsystems. Then, the dynamic energy function of subsystems reflecting the oscillation stability of the system is derived. Based on that, the dynamic energy flow path is described considering the introduction of LVRT control. On this basis, the interaction energy between LVRT control links and subsystems is analyzed, and the coupling mechanism of voltage support and damping characteristics in the LVRT process is explained. Further, aiming at the optimal change rate of the total interaction energy in the LVRT process, the adjustment strategy of LVRT control parameters is constructed to meet voltage and damping requirements. Finally, a PMSG-connected system model is built on the MATLAB/Simulink platform to verify the effectiveness of the adjustment strategy. The results show that the proposed method can effectively improve the damping level under the fault transient condition, as well as supporting system voltage.

The role of load modeling in power systems is crucial for both operational and regulatory considerations. It is essential to develop an effective and reliable method for optimizing load modeling parameter identification. In this paper, the dung beetle algorithm is improved by using the good point set, and a load model parameter identification strategy based on the good point set dung beetle optimization algorithm (GDBO) within the framework of the measurement-based load modeling method. The proposed parameter identification strategy involves utilizing PMU voltage data as input, selecting a comprehensive load model, and refining the initialization process based on the good point set to mitigate the influence of local maxima. Through iterative optimization of the objective function using the Dung Beetle Optimizer (DBO) algorithm, the optimal parameters for the comprehensive load model are determined, enhancing the model’s ability to accurately capture the power curve. Analysis of examples pertaining to PMU-measured modeling parameter identification reveals that the proposed GDBO algorithm, which incorporates a good point set, outperforms alternative methods such as the improved differential evolution algorithm (IDE), particle swarm optimization algorithm (PSO), grey wolf optimization algorithm (GWO), and conventional DBO algorithm. This demonstrates the superior performance of the introduced approach in the context of load model parameter identification.

Abstract Purpose In this study, we retrospectively investigated the prognostic role of pre-treatment neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in esophageal squamous cell carcinoma patients (ESCC) treated with concurrent chemo-radiotherapy (CCRT). Methods We retrospectively analyzed the records of 338 patients with pathologically diagnosed esophageal squamous cell carcinoma that underwent concurrent chemo-radiotherapy from January 2013 to December 2017. Univariate and multivariate analyses were used to identify prognostic factors for progression free survival (PFS) and overall survival (OS). Results The result showed that the thresholds for NLR and PLR were 2.47 and 136.0 by receiver operating characteristic curve. High NLR and PLR were both associated with tumor length (P

Abstract Activated microglia have been implicated in the pathogenesis of age-related macular degeneration (AMD), diabetic retinopathy, and other neurodegenerative and neuroinflammatory disorders, but our understanding of the mechanisms behind their activation is in infant stages. With the goal of identifying novel genes associated with microglial activation in the retina, we applied a semiquantitative fundus spot scoring scale to an unbiased, state-of-the-science mouse forward genetics pipeline. A mutation in the gene encoding the E3 ubiquitin ligase Herc3 led to prominent accumulation of fundus spots. CRISPR mutagenesis was used to generate Herc3 -/- mice, which developed prominent accumulation of fundus spots and corresponding activated Iba1 + /CD16 + subretinal microglia, retinal thinning on OCT and histology, and functional deficits by Optomotory and electrophysiology. Bulk RNA sequencing identified activation of inflammatory pathways and differentially expressed genes involved in the modulation of microglial activation. Thus, despite the known expression of multiple E3 ubiquitin ligases in the retina, we identified a non-redundant role for Herc3 in retinal homeostasis. Our findings are significant given that a dysregulated ubiquitin–proteasome system (UPS) is important in prevalent retinal diseases, in which activated microglia appear to play a role. This association between Herc3 deficiency, retinal microglial activation and retinal degeneration merits further study.

A two-layer scheduling method of energy storage that considers the uncertainty of both source and load is proposed to coordinate thermal power with composite energy storage to participate in the peak regulation of power systems. Firstly, considering the characteristics of thermal power deep peak regulation, a cost model of thermal power deep peak regulation is constructed and fuzzy parameters are used to manage the uncertainty of wind, photovoltaics, and load. Secondly, based on the peaking characteristics and operating costs of composite energy storage, a two-layer optimal scheduling model of energy storage is constructed. The upper layer takes pumped storage as the optimization goal to improve net load fluctuation and the optimal peak load benefit; the lower layer takes the system’s total peak load cost as the optimization goal and obtains a day-before scheduling plan for the energy storage system, using an improved gray wolf algorithm to process it. Finally, we verify the effectiveness of the proposed strategy based on an IEEE 39-node system.

Abstract The estrogen receptor (ER) designated ERα has actions in many cell and tissue types that impact glucose homeostasis. It is unknown if these include mechanisms in endothelial cells, which have the potential to influence relative obesity, and processes in adipose tissue and skeletal muscle that impact glucose control. Here we show that independent of impact on events in adipose tissue, endothelial ERα promotes glucose tolerance by enhancing endothelial insulin transport to skeletal muscle. Endothelial ERα-deficient male mice are glucose intolerant and insulin resistant, and in females the antidiabetogenic actions of estradiol (E2) are absent. The glucose dysregulation is due to impaired skeletal muscle glucose disposal that results from attenuated muscle insulin delivery. Endothelial ERα activation stimulates insulin transcytosis by skeletal muscle microvascular endothelial cells. Mechanistically this involves nuclear ERα-dependent upregulation of vesicular trafficking regulator sorting nexin 5 (SNX5) expression, and PI3 kinase activation that drives plasma membrane recruitment of SNX5. Thus, coupled nuclear and non-nuclear actions of ERα promote endothelial insulin transport to skeletal muscle to foster normal glucose homeostasis.

This paper takes the frame as the research object and explores the vibration characteristics of the frame to address the vibration problem of a 1-MSD straw-crushing and residual film recycling machine in the field operation process, and an accurate identification of the modal parameters of the frame is carried out to solve the resonance problem of the machine, which can achieve cost reduction and increase income to a certain extent. The first six natural frequencies of the frame are extracted by finite element modal identification and modal tests, respectively. The rationality of the modal test results is verified using the comprehensive modal and frequency response confidences. The maximum frequency error of modal frequency results of the two methods is only 6.61%, which provides a theoretical basis for the optimal design of the frame. In order to further analyze the resonance problem of the machine, the external excitation frequency of the machine during normal operation in the field is solved and compared with the first six natural frequencies of the frame. The results show that the first natural frequency of the frame (18.89 Hz) is close to the external excitation generated by the stripping roller (16.67 Hz). The first natural frequency and the volume of the frame are set as the optimization objectives, and the optimal optimization scheme is obtained by using the Optistruct solver, sensitivity method, and grey correlation method. The results indicate the first-order natural frequency of the optimized frame is 21.89 Hz, an increase of 15.882%, which is much higher than the excitation frequency of 16.67 Hz, and resonance can be avoided. The corresponding frame volume is 9.975 × 107 mm3, and the volume reduction is 3.46%; the optimized frame has good dynamic performance, which avoids the resonance of the machine and conforms to the lightweight design criteria of agricultural machinery structures. The research results can provide some theoretical reference for this kind of machine in solving the resonance problem and carrying out related vibration characteristics research.

A stringent DNA probe to profile microRNA (miRNA) expression within a specific cell remains a key challenge in biology. To address this issue, an intracellular ATP-activated Y-DNA probe for accurate imaging of miRNA in living cells was designed. Y-DNA was based on the fabrication of tripartite function modules, which consisted of a folate (FA)-modified targeting module, an ATP aptamer-sealed driver, and a miRNA sensing module. The Y-DNA probe could be specifically activated by ATP after it efficiently internalized into FA-receptor-overexpressed cells based on caveolar-mediated endocytosis, leading to the activation of the miRNA sensing module. The activated Y-DNA probe allowed for the imaging of miRNA in living cells with high sensitivity. The design of the ATP-activated Y-DNA sensor opens the door for bioorthogonal miRNA imaging and promotes the development of various responsive DNA molecular probes with enhanced anti-interference ability for clinical diagnosis.

Abstract Aberrant formation of biomolecular condensates has been proposed to play a role in several cancers. The oncogenic fusion protein BRD4-NUT forms condensates and drives changes in gene expression in Nut Carcinoma. Here we sought to understand the molecular elements of BRD4-NUT and its associated histone acetyltransferase (HAT), p300, that promote these activities. We determined that a minimal fragment of NUT (MIN) in fusion with BRD4 is necessary and sufficient to bind p300 and form condensates. Furthermore, a BRD4-p300 fusion protein also forms condensates and drives gene expression similarly to BRD4-NUT(MIN), suggesting the p300 fusion may mimic certain features of BRD4-NUT. The intrinsically disordered regions, transcription factor-binding domains, and HAT activity of p300 all collectively contribute to condensate formation by BRD4-p300, suggesting that these elements might contribute to condensate formation by BRD4-NUT. Conversely, only the HAT activity of BRD4-p300 appears necessary to mimic the transcriptional profile of cells expressing BRD4-NUT. Our results suggest a model for condensate formation by the BRD4-NUT:p300 complex involving a combination of positive feedback and phase separation, and show that multiple overlapping, yet distinct, regions of p300 contribute to condensate formation and transcriptional regulation.

With the increasing number of units involved in power system regulation and the increasing proportion of industrial load, a single data source has been unable to meet the accuracy requirements of online monitoring of unit conditions in the new power system. Based on the stacked autoencoder (SAE) network, combined with multi-source data fusion technology and adaptive threshold, a generator condition monitoring method is proposed. First, a SCADA–PMU data fusion method based on the weighted D–S evidence theory is proposed. Second, the auto-coding technology is introduced to build a stacked self-coding deep learning network model, extract the deep features of the training dataset, and build a generator fault detection model. Finally, by smoothing the reconstruction error and combining it with the trend change in the state monitoring quantity detected by the adaptive threshold, the fault judgment is realized. The simulation results show that, compared with the traditional method based on a single data source, the proposed method has higher robustness and accuracy, thus effectively improving the refinement level of generator condition monitoring.

Abstract Background After centuries of heavy reliance on fossil fuel energy, the world suffers from an energy crisis and global warming, calling for carbon emission reduction and a transition to clean energy. Microalgae have attracted much attention as a potential feedstock for biofuel production due to their high triacylglycerol content and CO2 sequestration ability. Many diacylglycerol acyltransferases (DGAT) species have been characterized, which catalyze the final committed step in triacylglycerol biosynthesis. However, the detailed structure–function features of DGATs and the role of the interactions among DGAT proteins in lipid metabolism remained largely unknown. Results In this study, the three characterized DGATs of Auxenochlorella protothecoides 2341 showed distinct structural and functional conservation. Functional complementation analyses showed that ApDGAT1 had higher activity than ApDGAT2b in yeast and model microalgae, and ApDGAT2a had no activity in yeast. The N-terminus was not essential to the catalysis function of ApDGAT1 but was crucial to ApDGAT2b as its enzyme activity was sensitive to any N-terminus modifications. Similarly, when acyl-CoA binding proteins (ACBPs) were fused to the N-terminus of ApDGAT1 and ApDGAT2b, zero and significant activity changes were observed, respectively. Interestingly, the ApACBP3 + ApDGAT1 variant contributed to higher oil accumulation than the original DGAT1, and ApACBP1 + ApDGAT1 fusion boosted oleic acid content in yeast. Overexpression of the three DGATs and the variation of ApACBP3 + ApDGAT1 increased the content of C18:1 of Chlamydomonas reinhardtii CC-5235. Significantly, ApDGAT1 interacted with itself, ApDGAT2b, and ApACBP1, which indicated that these three lipid metabolic proteins might have been a part of a dynamic protein interactome that facilitated the enrichment of oleic acid. Conclusions This study provided new insights into the functional and structural characteristics of DGATs and elucidated the importance of these physical interactions in potential lipid channeling.

Ultra-low-frequency oscillation (ULFO) is a new problem of frequency stability in asynchronous network back-end power networks. The negative damping provided by hydropower units is the direct cause of ultra-low-frequency oscillation, and DC modulation is an effective means of suppressing system frequency oscillation. Based on the transient energy function and the limitation of DC modulation, this paper analyzes the conditions of suppressing system oscillation by DC modulation from the perspective of energy. The weight of unit energy participation is defined, and the calculation formula of transient oscillation energy in a certain oscillation mode is derived. DC modulation sensitivity is then used to create a DC modulation sequence table based on the Prony identification approach. Ultimately, the DC involved in the modulation is identified using the DC modulation sequence table and the transient oscillation energy, and the Deep Deterministic Policy Gradient (DDPG) algorithm is used to optimize the chosen DC modulation parameters.

The appearance of ultra-low-frequency oscillations in the grid at the sending end, after asynchronous grid interconnection, poses a significant threat to the stable operation of the system. For post-asynchronous interconnection in a multi-DC transmission system, an investigation is conducted to analyze the causes of ultra-low-frequency oscillations and the utilization of a Frequency Limit Controller (FLC) which aims to suppress these oscillations. Furthermore, a method is developed to rank DC sensitivity, considering the hydroelectric distribution in the sending-end grid, by combining the DC FLC impact factor and DC control sensitivity. Subsequently, a novel approach for ultra-low-frequency oscillation suppression is proposed. This approach employs the stochastic subspace method for parameter estimation and the NSGA-II optimization algorithm to convert the multi-DC optimization challenge into multiple sequential cyclic optimization problems, each focusing on a single DC, ensuring a more effective suppression of ultra-low-frequency oscillations. The proposed scheme’s effectiveness is validated through simulations using a specific locations’ interconnected power grid.

The voltage source converter-based multi-terminal DC transmission (VSC-MTDC) system can use additional frequency control to respond to the frequency change of faulty AC system. However, the control coefficient of traditional additional frequency control is mostly fixed, and the control flexibility is insufficient, so it cannot be adjusted adaptively according to the frequency change of the system. Therefore, a frequency control strategy of the VSC-MTDC system based on fuzzy logic control is proposed. Based on the DC voltage slope controller, this strategy introduces an additional frequency controller based on fuzzy logic control, takes the frequency deviation and frequency change rate as the additional controller input, and dynamically adjusts the control quantity through the fuzzy logic control link to realize the adaptive adjustment of the VSC-MTDC system to the AC system’s frequency. Finally, a three-terminal flexible HVDC system is built on the PSCAD/EMTDC simulation platform for simulation verification. The results show that the proposed control strategy can effectively use the flexible DC system to support the frequency of the AC system and significantly improve the frequency stability of the faulty AC system.

SAP30 is a core subunit of the transcriptional corepressor SIN3 complex, but little is known about its role in gene regulation and human cancer. Here, we show that SAP30 was a nonmutational oncoprotein upregulated in more than 50% of human breast tumors and correlated with unfavorable outcomes in patients with breast cancer. In various breast cancer mouse models, we found that SAP30 promoted tumor growth and metastasis through its interaction with SIN3A/3B. Surprisingly, the canonical gene silencing role was not essential for SAP30’s tumor-promoting actions. SAP30 enhanced chromatin accessibility and RNA polymerase II occupancy at promoters in breast cancer cells, acting as a coactivator for genes involved in cell motility, angiogenesis, and lymphangiogenesis, thereby driving tumor progression. Notably, SAP30 formed a homodimer with 1 subunit binding to SIN3A and another subunit recruiting MLL1 through specific Phe186/200 residues within its transactivation domain. MLL1 was required for SAP30-mediated transcriptional coactivation and breast tumor progression. Collectively, our findings reveal that SAP30 represents a transcriptional dependency in breast cancer.

Asphalt mixture has complex gradation and mesostructure. Accurate prediction of the relationship between gradation and mesostructure is of great significance for the establishment of mesostructure numerical simulation model and image-based gradation detection. In this paper, featurization, stepwise regression, econometric hypothesis test are utilized for establishing the predicting models. Firstly, asphalt mixtures with 64 kinds of gradation are scanned by Computed Tomography (CT) to obtain the mesostructure images; Then a series of mesostructure parameters of voids and aggregates are put forward. On this basis, the relationship model between gradation and mesostructure is established and verified by featurization and statistical modeling method. The results show that for predicting the passing percentage of the 4.75 mm sieve and the mean value of average distance between aggregate centroids for 9.5–4.75 mm aggregates, the prediction error of passing percentage is acceptable. It illustrates that the relationship model between gradation and mesostructure established by statistical method is effective, and it is significance for material design and testing under the condition of big data in the future.

Abstract Background The spine is the most frequently affected part of the skeletal system to metastatic tumors. External radiotherapy is considered the first-line standard of care for these patients with spine metastases. Recurrent spinal metastases after radiotherapy cannot be treated with further radiotherapy within a short period of time, making treatment difficult. We aimed to evaluate the effectiveness and safety of MWA combined with cementoplasty in the treatment of spinal metastases after radiotherapy under real-time temperature monitoring. Methods In this retrospective study, 82 patients with 115 spinal metastatic lesions were treated with MWA and cementoplasty under real-time temperature monitoring. Changes in visual analog scale (VAS) scores, daily morphine consumption, and Oswestry Disability Index (ODI) scores were noted. A paired Student’s t-test was used to assess these parameters. Complications during the procedure were graded using the CTCAE version 5.0. Results Technical success was attained in all patients. The mean VAS score was 6.3 ± 2.0 (range, 4–10) before operation, and remarkable decline was noted in one month (1.7 ± 1.0 [P

Neurofibromatosis type 1 (NF1) is one of the most common tumor-predisposing genetic disorders. Neurofibromas are NF1-associated benign tumors. A hallmark feature of neurofibromas is an abundant collagen-rich extracellular matrix (ECM) that constitutes more than 50% of the tumor dry weight. However, little is known about the mechanism underlying ECM deposition during neurofibroma development and treatment response. We performed a systematic investigation of ECM enrichment during plexiform neurofibroma (pNF) development and identified basement membrane (BM) proteins, rather than major collagen isoforms, as the most upregulated ECM component. Following MEK inhibitor treatment, the ECM profile displayed an overall downregulation signature, suggesting ECM reduction as a therapeutic benefit of MEK inhibition. Through these proteomic studies, TGF-β1 signaling was identified as playing a role in ECM dynamics. Indeed, TGF-β1 overexpression promoted pNF progression in vivo. Furthermore, by integrating single-cell RNA sequencing, we found that immune cells including macrophages and T cells produce TGF-β1 to induce Schwann cells to produce and deposit BM proteins for ECM remodeling. Following Nf1 loss, neoplastic Schwann cells further increased BM protein deposition in response to TGF-β1. Our data delineate the regulation governing ECM dynamics in pNF and suggest that BM proteins could serve as biomarkers for disease diagnosis and treatment response.

A trend in the development of spaceborne Synthetic Aperture Radar (SAR) technology is the shift from a single-satellite repeated observation mode to a multi-satellite collaborative observation mode. However, current multi-satellite collaborative geolocation algorithms face challenges, such as geometric model mismatch and poor baseline estimation accuracy, arising from highly dynamic changes among multi-satellites. This paper introduces a high-precision and efficient geolocation algorithm for a spaceborne bistatic interferometric SAR (BiInSAR) system based on an improved range–Doppler (IRD) model. The proposed algorithm encompasses three key contributions. Firstly, a comprehensive description of the spatial baseline geometric model unique to the bistatic configuration is provided, with a specific focus on deriving the perpendicular baseline expression. Secondly, IRD geolocation functions are established to meet the specific requirements of the bistatic configuration. Then, a novel BiInSAR geolocation algorithm based on the IRD’s functions is proposed, which can significantly improve the target geolocation accuracy by modifying the range–Doppler equation to suit the bistatic configuration. Meanwhile, a low-coupling parallel calculation method is proposed, which can improve the calculation speed by two to three times. Finally, the accuracy and efficiency of the algorithm are demonstrated using experimental data acquired by the TH-2 satellite, which is China’s first spaceborne BiInSAR system. The experimental results prove that the IRD algorithm exhibits geolocation accuracy with an average error of less than 1 m and a standard deviation of less than 2.5 m while maintaining computational efficiency at a calculation speed of 1,429,678 pixels per second.

Polarimetric Synthetic Aperture Radar (PolSAR) data is inherently characterized by speckle noise, which significantly deteriorates certain aspects of the quality of the PolSAR data processing, including the polarimetric decomposition and target interpretation. With the rapid increase in PolSAR resolution, SAR images in complex natural and artificial scenes exhibit non-homogeneous characteristics, which creates an urgent demand for high-resolution PolSAR filters. To address these issues, a new adaptive PolSAR filter based on joint similarity measure criterion (JSMC) is proposed in this paper. Firstly, a scale-adaptive filtering window is established in order to preserve the texture structure based on a multi-directional ratio edge detector. Secondly, the JSMC is proposed in order to accurately select homogeneous pixels; it describes pixel similarity based on both space distance and polarimetric distance. Thirdly, the homogeneous pixels are filtered based on statistical averaging. Finally, the airborne and spaceborne real data experiment results validate the effectiveness of our proposed method. Compared with other filters, the filter proposed in this paper provides a better outcome for PolSAR data in speckle suppression, edge texture, and the preservation of polarimetric properties.

PurposeTo evaluate the efficacy safety of computed tomography (CT)-guided 125I seed implantation by coplanar template for vertebral metastases after failure of external beam radiation therapy (EBRT).Material and methodsRetrospective analysis of the clinical outcomes of 58 patients with vertebral metastases after failure of EBRT, who underwent 125I seed implantation as a salvage treatment with a CT-guided coplanar template-assisted technique from January 2015 to January 2017.ResultsThe mean post-operative NRS score decreased significantly at T4w (3.5 ± 0.9, p0.05).Conclusions125I seed implantation can be used as a salvage treatment for patients with vertebral metastases after failure of EBRT.

ABSTRACT Viruses are known to co-opt host machinery for translation initiation, but less is known about which host factors are required for the formation of ribosomes used to synthesize viral proteins. Using a loss-of-function CRISPR screen, we show that synthesis of a flavivirus-encoded fluorescent reporter depends on multiple host factors, including several 60S ribosome biogenesis proteins. Viral phenotyping revealed that two of these factors, SBDS, a known ribosome biogenesis factor, and the relatively uncharacterized protein SPATA5, were broadly required for replication of flaviviruses, coronaviruses, alphaviruses, paramyxoviruses, an enterovirus, and a poxvirus. Mechanistic studies revealed that loss of SPATA5 caused defects in rRNA processing and ribosome assembly, suggesting that this human protein may be a functional ortholog of yeast Drg1. These studies implicate specific ribosome biogenesis proteins as viral host dependency factors that are required for synthesis of virally encoded protein and accordingly, optimal viral replication. IMPORTANCE Viruses are well known for their ability to co-opt host ribosomes to synthesize viral proteins. The specific factors involved in translation of viral RNAs are not fully described. In this study, we implemented a unique genome-scale CRISPR screen to identify previously uncharacterized host factors that are important for the synthesis of virally encoded protein. We found that multiple genes involved in 60S ribosome biogenesis were required for viral RNA translation. Loss of these factors severely impaired viral replication. Mechanistic studies on the AAA ATPase SPATA5 indicate that this host factor is required for a late step in ribosome formation. These findings reveal insight into the identity and function of specific ribosome biogenesis proteins that are critical for viral infections.

Abstract Two‐dimensional (2D) MXene‐based nanofiltration membranes could sustainably and rapidly produce clean water. However, the challenges related to the severe swelling of the MXene membranes in water should be overcome before the practical application. In this work, the negatively charged MXene‐based membrane is modified by positively charged polyethyleneimine (PEI) with various PEI:MXene ratios. The PEI‐MXene is deposited on a polyacrylonitrile (PAN) substrate as a top membrane to prepare an anti‐swelling composite PEI‐MXene/PAN membranes with outstanding mechanical strength and stability. Interestingly, when the interlayer spacing of the top Mxene layers are tuned between ca. 14.15 and ca. 14.52 Å, the resultant PEI‐MXene/PAN membranes exhibit the excellent ability of size sieving. For instance, PEI‐MXene(1:1)/PAN membrane presents high flux performance to Acid Blue 90 (AB90), Congo Red (CR), and Direct Red 80 (DR80) (i.e., 563.9, 882.6, and 633.6 L m−2 h−1, respectively) at 0.2 MPa, and remarkable rejection rates, that is, 99.3%, 99.82%, and 99.9%, respectively. Besides, the PEI‐MXene(0.5:1)/PAN possesses the highest flux of 1528.1 L m−2 h−1 and outstanding rejection rate of 99.9% to dye of AB8GX. Moreover, the proposed strategy can be extended to the modification of other 2D material nanofiltration membranes.

Objective: Seventy percent of Fuchs’ endothelial corneal dystrophy (FECD) cases are caused by an intronic trinucleotide repeat expansion in the transcription factor 4 gene (TCF4). The objective of this study was to characterize the corneal subbasal nerve plexus and corneal haze in patients with FECD with (RE+) and without the trinucleotide repeat expansion (RE−) and to assess the correlation of these parameters with disease severity. Design: Cross-sectional, single-center study. Participants: Fifty-two eyes of 29 subjects with a modified Krachmer grade of FECD severity from 1 to 6 were included in the study. Fifteen of the 29 subjects carried an expanded TCF4 allele length of ≥ 40 cytosine-thymine-guanine repeats (RE+). Main Outcomes Measures: In vivo confocal microscopy assessments of corneal nerve fiber length (CNFL), corneal nerve branch density, corneal nerve fiber density (CNFD), and anterior corneal stromal backscatter (haze); Scheimpflug tomography densitometry measurements of haze in anterior, central, and posterior corneal layers. Results: Using confocal microscopy, we detected a negative correlation between FECD severity and both CNFL and CNFD in the eyes of RE+ subjects (Spearman ρ = −0.45, P = 0.029 and ρ = −0.62, P = 0.0015, respectively) but not in the eyes of RE− subjects. Additionally, CNFD negatively correlated with the repeat length of the expanded allele in the RE+ subjects (Spearman ρ = −0.42, P = 0.038). We found a positive correlation between anterior stromal backscatter and severity in both the RE+ and RE− groups (ρ = 0.60, P = 0.0023 and ρ = 0.44, P = 0.024, respectively). The anterior, central, and posterior Scheimpflug densitometry measurements also positively correlated with severity in both the RE+ and RE− groups (P = 5.5 × 10−5, 2.5 × 10−4, and 2.9 × 10−4, respectively, after adjusting for the expansion status in a pooled analysis. However, for patients with severe FECD (Krachmer grades 5 and 6), the posterior densitometry measurements were higher in the RE+ group than in the RE− group (P < 0.05). Conclusions: Loss of corneal nerves in FECD supports the classification of the TCF4 trinucleotide repeat expansion disorder as a neurodegenerative disease. Haze in the anterior, central, and posterior cornea correlate with severity, irrespective of the genotype. Quantitative assessments of corneal nerves and corneal haze may be useful to gauge and monitor FECD disease severity in RE+ patients.

Abstract Diffusely infiltrating gliomas are among the most common central nervous system tumors in adults. Over the past decade, the subcategorization of these tumors has changed to include both traditional histologic features and more recently identified molecular factors. However, one molecular feature that has yet to be integrated is the presence/absence of chromosomal instability (CIN). Herein, we use global methylation profiling to evaluate a reference cohort of IDH-mutant astrocytomas with and without prior evidence of CIN (n = 42), and apply the resulting methylation-based characteristics to a larger test cohort of publicly-available IDH-mutant astrocytomas (n = 245). We demonstrate that IDH-mutant astrocytomas with evidence of CIN cluster separately from their chromosomally-stable counterparts. CIN cases were associated with higher initial histologic grade, altered expression patterns of genes related to CIN in other cancers, elevated initial total copy number burden, and significantly worse progression-free and overall survival. In addition, in a grade-for-grade analysis, patients with CIN-positive WHO grade 2 and 3 tumors had significantly worse survival. These results suggest that global methylation profiling can be used to discriminate between chromosomally stable and unstable IDH-mutant astrocytomas, and may therefore provide a reliable and cost-effective method for identifying gliomas with chromosomal instability and resultant poor clinical outcome.

Abstract This paper proposes an intelligent Deep Learning (DL) based approach for Data‐Driven Security‐Constrained Unit Commitment (DD‐SCUC) decision‐making. The proposed approach includes data pre‐processing and a two‐stage decision‐making process. Firstly, historical data is accumulated and pre‐processed. Then, the DD‐SCUC model is created based on the Gated Recurrent Unit‐Neural Network (GRU‐NN). The mapping model between system daily load and decision results is created by training the DL model with historical data and then is utilized to make SCUC decisions. The two‐stage decision‐making process outputs the decision results based on various applications and scenarios. This approach has self‐learning capabilities because the accumulation of historical data sets can revise the mapping model and therefore improve its accuracy. Simulation results from the IEEE 118‐bus test system and a real power system from China showed that compared with deterministic Physical‐Model‐Driven (PMD)‐SCUC methods, the approach has higher accuracy, better efficiency in the practical use case, and better adaptability to different types of SCUC problems.

Abstract Autism spectrum disorder (ASD) is a collection of neurodevelopmental disorders characterized by deficits in social communication and restricted, repetitive patterns of behavior or interests. ASD is highly heritable, but genetically and phenotypically heterogeneous, reducing the power to identify causative genes. We performed whole genome sequencing (WGS) in an ASD cohort of 68 individuals from 22 families enriched for recent shared ancestry. We identified an average of 3.07 million variants per genome, of which an average of 112,512 were rare. We mapped runs of homozygosity (ROHs) in affected individuals and found an average genomic homozygosity of 9.65%, consistent with expectations for multiple generations of consanguineous unions. We identified potentially pathogenic rare exonic or splice site variants in 12 known (including KMT2C, SCN1A, SPTBN1, SYNE1, ZNF292) and 12 candidate (including CHD5, GRB10, PPP1R13B) ASD genes. Furthermore, we annotated noncoding variants in ROHs with brain-specific regulatory elements and identified putative disease-causing variants within brain-specific promoters and enhancers for 5 known ASD and neurodevelopmental disease genes (ACTG1, AUTS2, CTNND2, CNTNAP4, SPTBN4). We also identified copy number variants in two known ASD and neurodevelopmental disease loci in two affected individuals. In total we identified potentially etiological variants in known ASD or neurodevelopmental disease genes for ~61% (14/23) of affected individuals. We combined WGS with homozygosity mapping and regulatory element annotations to identify candidate ASD variants. Our analyses add to the growing number of ASD genes and variants and emphasize the importance of leveraging recent shared ancestry to map disease variants in complex neurodevelopmental disorders.

RIPK1 regulates inflammation and cell death and is inhibited by phosphorylation on numerous residues. Here, the authors use a CRISPR whole genome screen to identify that protein phosphatase 1 regulatory subunit 3G regulates RIPK1 apoptotic and necroptotic activity as well as inflammation.

Sustainable and resilient pavement infrastructure is critical for current economic and environmental challenges. In the past 10 years, the pavement infrastructure strongly supports the rapid development of the global social economy. New theories, new methods, new technologies and new materials related to pavement engineering are emerging. Deterioration of pavement infrastructure is a typical multi-physics problem. Because of actual coupled behaviors of traffic and environmental conditions, predictions of pavement service life become more and more complicated and require a deep knowledge of pavement material analysis. In order to summarize the current and determine the future research of pavement engineering, Journal of Traffic and Transportation Engineering (English Edition) has launched a review paper on the topic of “New innovations in pavement materials and engineering: A review on pavement engineering research 2021”. Based on the joint-effort of 43 scholars from 24 well-known universities in highway engineering, this review paper systematically analyzes the research status and future development direction of 5 major fields of pavement engineering in the world. The content includes asphalt binder performance and modeling, mixture performance and modeling of pavement materials, multi-scale mechanics, green and sustainable pavement, and intelligent pavement. Overall, this review paper is able to provide references and insights for researchers and engineers in the field of pavement engineering.

Abnormalities in CD4+ T cell (Th cell) differentiation play an important role in the pathogenesis of viral myocarditis (VMC). Our previous studies demonstrated that activation of the cholinergic anti-inflammatory pathway (CAP) alleviated the inflammatory response. In addition, we observed that right cervical vagotomy aggravates VMC by inhibiting CAP. However, the vagus nerve’s effect on differentiation of CD4+ T cells has not been studied in VMC mice to date. In this study, we investigated the effects of cervical vagotomy and the α7nAChR agonist pnu282987 on CD4+ T cell differentiation in a murine myocarditis model (BALB/c) infected with coxsackievirus B3 (CVB3). Splenic CD4+ T cells from CVB3-induced mice obtained and cultured to investigate the potential mechanism of CD4+ T cell differentiation. Each Th cell subset was analyzed by flow cytometry. Our results showed that right cervical vagotomy increased proportions of Th1 and Th17 cells and decreased proportions of Th2 and Treg cells in the spleen. Vagotomy-induced upregulation of T-bet, Ror-γ, IFN-γ, and IL-17 expression while downregulating the expression of Gata3, Foxp3, and IL-4 in the heart. In addition, we observed upregulated levels of proinflammatory cytokines, aggravated myocardial lesions and cellular infiltration, and worsened cardiac function in VMC mice. Pnu282987 administration reversed these outcomes. Furthermore, vagotomy inhibited JAK2-STAT3 activation and enhanced NF-κB activation in splenic CD4+ T cells. The CD4+ T cell differentiation was related to JAK2-STAT3 and NF-κB signal pathways. In conclusion, vagus nerve modulates the inflammatory response by regulating CD4+ T cell differentiation in response to VMC.

Multiple genetic loci have been reported for progeroid syndromes. However, the molecular defects in some extremely rare forms of progeria have yet to be elucidated. Here, we report a 21-year-old man of Chinese ancestry who has an autosomal recessive form of progeria, characterized by severe dwarfism, mandibular hypoplasia, hyperopia, and partial lipodystrophy. Analyses of exome sequencing data from the entire family revealed only 1 rare homozygous missense variant (c.86C>T; p.Pro29Leu) in TOMM7 in the proband, while the parents and 2 unaffected siblings were heterozygous for the variant. TOMM7, a nuclear gene, encodes a translocase in the outer mitochondrial membrane. The TOMM complex makes up the outer membrane pore, which is responsible for importing many preproteins into the mitochondria. A proteomic comparison of mitochondria from control and proband-derived cultured fibroblasts revealed an increase in abundance of several proteins involved in oxidative phosphorylation, as well as a reduction in abundance of proteins involved in phospholipid metabolism. We also observed elevated basal and maximal oxygen consumption rates in the fibroblasts from the proband as compared with control fibroblasts. We concluded that altered mitochondrial protein import due to biallelic loss-of-function TOMM7 can cause severe growth retardation and progeroid features.

Abstract To obtain a short flux path and improve the torque performance, a double‐phase excitation (DE) was generally used for switched reluctance motor (SRM). But the torque ripple of the SRM working under DE with traditional winding distribution increases because of the inconsistent electromagnetic field. To deal with this problem, an 8/6 SRM working under DE with novel winding distribution (DESRM) is proposed here. In order to comprehensively analyse the electromagnetic performance of DESRM, it is compared with a traditional single‐excitation SRM and double‐excitation SRM with traditional winding, in terms of air flux density, radial and tangential force components, inductance, torque, and losses. The theoretical and finite element analysis results reveal the cause of differences on torque and vibration of the motor as well as the mechanism of generating different motor performance. In addition, the analysis shows that the proposed DESRM generates a higher torque with a reduced torque ripple. Finally, a pair of prototypes with different winding configurations is designed and used to verify the theoretical analysis.

This study proposes an online finite-time adaptive parameter estimation method for grid-connected voltage source inverter (VSI) with LCL filter. In this framework, a time-continuous state-space system model is first developed, which is different from the nonparametric frequency-response-based method. Then, the parameter estimation error information is extracted by introducing a series of filter operations. Moreover, a sliding mode term is studied and cooperated with the obtained parameter estimation error to design the parameter estimation error-based finite-time adaptive parameter estimation algorithm. With the help of this novel adaptive law, the physical parameters of electrical components can be driven to their true values accurately and fast. Theoretical analysis is conducted in terms of the Lyapunov theory to demonstrate the convergence of the parameter estimation error. Finally, numerical simulation results are provided to illustrate the superiority of the proposed method over the conventional method.

Background: An in silico screen was performed to identify FDA approved drugs that inhibit SARS-CoV-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication.Methods: A 2-center, randomized, double-blind, placebo-controlled trial was performed among patients hospitalized with COVID-19 infection. Enrolled patients were randomized 2:1 to atovaquone 1500 mg BID versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Saliva was collected at baseline and twice per day for up to 10 days for RNA extraction for SARS-CoV-2 viral load measurement by quantitative reverse-transcriptase PCR. The primary outcome was the between group difference in log-transformed viral load (copies/mL) using a generalized linear mixed-effect models of repeated measures from all samples.Results: Of the 61 patients enrolled; 41 received atovaquone and 19 received placebo. Overall, the population was predominately male (63%) and Hispanic (70%), with a mean age of 51 years, enrolled a mean of 5 days from symptom onset. The log10 viral load was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Change in viral load did not differ over time between the atovaquone plus standard of care arm versus the placebo plus standard of care arm. Pharmacokinetic (PK) studies of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, with an inverse correlation between BMI and atovaquone levels, (Rho −0.45, p = 0.02). In post hoc analysis, an inverse correlation was observed between atovaquone levels and viral load (Rho −0.54, p = 0.005).Conclusion: In this prospective, randomized, placebo-controlled trial, atovaquone did not demonstrate evidence of enhanced SARS-CoV-2 viral clearance compared with placebo. However, based on the observed inverse correlation between atovaquone levels and viral load, additional PK-guided studies may be warranted to examine the antiviral effect of atovaquone in COVID-19 patients.

Cohesin folds chromosomes via DNA loop extrusion. Cohesin-mediated chromosome loops regulate transcription by shaping long-range enhancer–promoter interactions, among other mechanisms. Mutations of cohesin subunits and regulators cause human developmental diseases termed cohesinopathy. Vertebrate cohesin consists of SMC1, SMC3, RAD21, and either STAG1 or STAG2. To probe the physiological functions of cohesin, we created conditional knockout (cKO) mice with Stag2 deleted in the nervous system. Stag2 cKO mice exhibit growth retardation, neurological defects, and premature death, in part due to insufficient myelination of nerve fibers. Stag2 cKO oligodendrocytes exhibit delayed maturation and downregulation of myelination-related genes. Stag2 loss reduces promoter-anchored loops at downregulated genes in oligodendrocytes. Thus, STAG2-cohesin generates promoter-anchored loops at myelination-promoting genes to facilitate their transcription. Our study implicates defective myelination as a contributing factor to cohesinopathy and establishes oligodendrocytes as a relevant cell type to explore the mechanisms by which cohesin regulates transcription.

Purpose: To analyze the outcome and prognosis of patients with refractory cervical lymph node metastasis of thoracic esophageal squamous cell carcinoma after external irradiation, who underwent interstitial 125 I brachytherapy as a salvage treatment with a CT-guided coplanar template-assisted technique. We also want to compare the dosimetry of 3D printed coplanar template-assisted interstitial 125 I brachytherapy preoperative and postoperative, and to explore the accuracy of this technology. Material and methods: We retrospectively collected and analyzed the results of 32 patients with refractory cervical lymph node metastasis of thoracic esophageal squamous cell carcinoma after external irradiation, who underwent interstitial 125 I brachytherapy as a salvage treatment with a CT-guided coplanar template-assisted technique from January 2012 to December 2017. Results: The actual D90 were 114 to 240 Gy, and the median postoperative dosimetry assessment was 177.5 Gy. The local control rates at 3, 6, 9, and 12 months were 87.5%, 59.38%, 40.63%, and 31.25%, respectively. The median local control time was 7.5 months. The median overall survival time was 10.5 months (95% CI, 8.9-13.4), and the survival rates of 1- and 2-year, respectively, were 43.75% and 9.38%. There were 36 lesions in 32 patients. By performing a paired t -test analysis, there was no significant difference in D90, D100, V100, V150, V200, GTV volume, CI, EI, and HI between preoperative and postoperative ( P > .05). Conclusions: Interstitial 125 I brachytherapy can be used as a salvage treatment for patients with refractory cervical lymph node metastasis of thoracic esophageal squamous cell carcinoma after external irradiation. With the auxiliary function of 3D printed coplanar template, the main dosimetry parameters verified after the operation can meet the requirements of the preoperative plan with good treatment accuracy.

When traditional STATCOM (Static Synchronous Compensator) performs large-capacity reactive power compensation, the control accuracy of the DC side voltage will be affected and the DC side voltage will fluctuate greatly. Therefore, this study proposes to use battery energy storage STATCOM (STATCOM/BESS) and gives the main circuit topology of STATCOM/BESS. By analyzing the working principle of STATCOM/BESS, the mathematical model and control method are derived and modeled, in which the Shepherd model is used as the energy storage battery in STATCOM/BESS. Aiming at the possible imbalance of the battery state of charge (SOC) in STATCOM/BESS, the phase-to-phase SOC balance control and phase control are proposed. At last, in PSCAD/EMTDC simulation software, STATCOM/BESS is tested for dynamic response and steady-state response performance of active power control, reactive power control, and transformation failure suppression test, which verifies the effectiveness and superiority of STATCOM/BESS commutation failure.

FOXA2 encodes a transcription factor mutated in 10% of endometrial cancers (ECs), with a higher mutation rate in aggressive variants. FOXA2 has essential roles in embryonic and uterine development. However, FOXA2’s role in EC is incompletely understood. Functional investigations using human and mouse EC cell lines revealed that FOXA2 controls endometrial epithelial gene expression programs regulating cell proliferation, adhesion, and endometrial-epithelial transition. In live animals, conditional inactivation of Foxa2 or Pten alone in endometrial epithelium did not result in ECs, but simultaneous inactivation of both genes resulted in lethal ECs with complete penetrance, establishing potent synergism between Foxa2 and PI3K signaling. Studies in tumor-derived cell lines and organoids highlighted additional invasion and cell growth phenotypes associated with malignant transformation and identified key mediators, including Myc and Cdh1. Transcriptome and cistrome analyses revealed that FOXA2 broadly controls gene expression programs through modification of enhancer activity in addition to regulating specific target genes, rationalizing its tumor suppressor functions. By integrating results from our cell lines, organoids, animal models, and patient data, our findings demonstrated that FOXA2 is an endometrial tumor suppressor associated with aggressive disease and with shared commonalities among its roles in endometrial function and carcinogenesis.

Mechanical properties, workability and pore structures of foamed concrete (FC) reinforced with different fibres were investigated. In order to characterise the cementitious matrix with entrained bubbles and fibres, X-ray computed tomography (X-CT) technology and Digital image correlation (DIC) technique were employed to analyse the pore structure and the real-time strain field distributions under applied loads, respectively. The results demonstrated that the inherent properties of fibres, including density, modulus and wettability, and bond performance between the cement matrix and fibres are two main factors in determining the mechanical properties of the fibre reinforced FC. Meanwhile, the fibres also had an influence on the workability and rheological properties of fresh FC slurry through changing the bubble numbers and distributions in the slurry. According to the strain analysis during the bending tests using the DIC technique, it was found that carbon fibre and polyacrylonitrile fibre were conducive to distributing the strain field in the FC in a homogeneous fashion and delayed crack widening after the peak loads effectively.

Animal development is mediated by a surprisingly small set of canonical signaling pathways such as Wnt, Hedgehog, TGF-beta, Notch, and Hippo pathways. Although once thought to be present only in animals, recent genome sequencing has revealed components of these pathways in the closest unicellular relatives of animals. These findings raise questions about the ancestral functions of these developmental pathways and their potential role in the emergence of animal multicellularity. Here, we provide the first functional characterization of any of these developmental pathways in unicellular organisms by developing techniques for genetic manipulation in Capsaspora owczarzaki, a close unicellular relative of animals that displays aggregative multicellularity. We then use these tools to characterize the Capsaspora ortholog of the Hippo signaling nuclear effector YAP/TAZ/Yorkie (coYki), a key regulator of tissue size in animals. In contrast to what might be expected based on studies in animals, we show that coYki is dispensable for cell proliferation but regulates cytoskeletal dynamics and the three-dimensional (3D) shape of multicellular structures. We further demonstrate that the cytoskeletal abnormalities of individual coYki mutant cells underlie the abnormal 3D shape of coYki mutant aggregates. Taken together, these findings implicate an ancestral role for the Hippo pathway in cytoskeletal dynamics and multicellular morphogenesis predating the origin of animal multicellularity, which was co-opted during evolution to regulate cell proliferation.

This paper studies the user-defined modeling (UDM) method in PSS/E and applies it to a modular multilevel converter high-voltage direct current (MMC-HVDC) system. First, the mechanism of PSS/E UDM is discussed, including the requirements of the model call, storage space allocation, and flows of dynamic simulation. Then, a generic UDM method applicable to various objects is proposed in PSS/E, considering both the internal structures of models and their interfaces with the PSS/E main program. Next, the design of multiple time scales of UDM is presented for hybrid step size simulation. Accordingly, a user-defined MMC-HVDC system model is built in PSS/E considering the converter, DC-line, control system, and system interface. Finally, the model is compared with a PSCAD electromagnetic transient MMC-HVDC model in a modified two-area-four-generator system. The simulation results demonstrate the proposed UDM method.

Abstract Background Particulate matter (PM) is strongly linked to human health and has detrimental effects on the eye. Studies have, however, focused on the ocular surface, with limited research on the impact of PM2.5 on intraocular pressure (IOP). Methods To investigate the impact of PM2.5 on IOP and the associated mechanism, C57BL/6 mouse eyes were topically exposed to a PM2.5 suspension for 3 months, and human trabecular meshwork (HTM) cells were subjected to various PM2.5 concentrations in vitro. Cell viability, NLRP3/caspase-1, IL-1β, and GSDMD expression, reactive oxygen species (ROS) production and cell contractility were measured by western blot, ELISA, cell counting kit-8, ROS assay kit or a cell contractility assay. ROS scavenger N-acetyl-L-cysteine (NAC) and caspase-1 inhibitor VX-765 were used to intervene in PM2.5-induced damages. Results The results revealed that the IOP increased gradually after PM2.5 exposure, and upregulations of the NLRP3 inflammasome, caspase-1, IL-1β, and GSDMD protein levels were observed in outflow tissues. PM2.5 exposure decreased HTM cell viability and affected contraction. Furthermore, elevated ROS levels were observed as well as an activation of the NLRP3 inflammasome and downstream inflammatory factors caspase-1 and IL-1β. NAC improved HTM cell viability, inhibited the activation of the NLRP3 inflammasome axis, and HTM cell contraction by scavenging ROS. VX-765 showed similar protection against the PM2.5 induced adverse effects. Conclusion This study provides novel evidence that PM2.5 has a direct toxic effect on intraocular tissues and may contribute to the initiation and development of ocular hypertension and glaucoma. This occurs as a result of increased oxidative stress and the subsequent induction of NLRP3 inflammasome mediated pyroptosis in trabecular meshwork cells.

Abstract Neurofibromatosis Type I (NF1) is a neurocutaneous genetic syndrome characterized by a wide spectrum of clinical presentations, including benign peripheral nerve sheath tumor called neurofibroma. These tumors originate from the Schwann cell lineage but other cell types as well as extracellular matrix (ECM) in the neurofibroma microenvironment constitute the majority of the tumor mass. In fact, collagen accounts for up to 50% of the neurofibroma’s dry weight. Although the presence of collagens in neurofibroma is indisputable, the exact repertoire of ECM genes and ECM-associated genes (i.e. the matrisome) and their functions are unknown. Here, transcriptome profiling by single-cell RNA sequencing reveals the matrisome of human cutaneous neurofibroma (cNF). We discovered that classic pro-fibrogenic collagen I myofibroblasts are rare in neurofibroma. In contrast, collagen VI, a pro-tumorigenic ECM, is abundant and mainly secreted by neurofibroma fibroblasts. This study also identified potential cell type-specific markers to further elucidate the biology of the cNF microenvironment.

In view of the UHV multiterminal hybrid DC transmission system, the DC line protection with universal applicability, fast response speed, stability, and reliability is particularly important for its safe and economic operation. In this article, the boundary frequency characteristics of the UHV multiterminal hybrid DC transmission system are analyzed by considering the DC boundary of the rectifier side and inverter side, line frequency variation, and other factors. According to the fact that the boundary of the fault line has a strong attenuation effect on the high-frequency component of the transient current, a protection method based on the intrinsic mode energy entropy is proposed to distinguish the faults inside and outside. The criterion to initiate the protection is constructed by using the amplitude of the transient power; the fault direction criterion is constructed by using the positive and negative characteristics of the transient energy of the fault power detected by power direction elements on both sides of the T-zone; the fault pole selection criterion is constructed by using the ratio of low-frequency transient power changes of positive and negative poles. Finally, the Kun–Liu–Long line UHV three-terminal hybrid DC transmission system model is built on the PSCAD/EMTDC simulation platform, and a large number of simulation examples verify that the protection can operate reliably under different fault poles, fault positions, and transition resistances.

This study researches on the Wudongde hybrid multi-terminal Ultra High-Voltage Direct Current Transmission (UHVDC) project (referred to as Wudongde transmission project in short) from the electromagnetic transient model and simulation and establishes an accurate simulation model of the hybrid multi-terminal UHVDC transmission system with the Power Systems Computer-Aided Design (PSCAD). The hybrid multi-terminal UHVDC transmission system consists of the primary system and the control system. The simulation model of the primary system adopts the parameters of the Wudongde transmission project, and the simulation model of the control system refers to the control system benchmark model of HVDC transmission and 9-terminal DC grid in the International Council on Large Electric Systems (CIGRE). According to the characteristics of the hybrid multi-terminal UHVDC control system, the benchmark model of HVDC transmission and 9-terminal DC grid control system in the CIGRE is modified accordingly, and a simulation model of the control system applicable to the hybrid multi-terminal UHVDC transmission system is established. The accuracy and credibility of the model are verified through the comparison of the recording waveform and the simulating waveform of the steady-state and transient operation. The simulating and field recording waveforms show that the model can accurately simulate the Wudongde transmission project and be used as an effective tool for further studying the electromagnetic transient characteristics of the hybrid multi-terminal UHVDC transmission system.