Research on resilience assessment method of train control on-board system.

To address the problem of difficult performance assessment of train control on-board system after recovery from failures, we have proposed a resilience assessment methodology that uses reliability as an indicator of system resilience. Since the system failures are time-dependent, we adopted the Discrete Time Bayesian Network method to obtain the system's reliability before and after failure. Subsequently, we used an exponential recovery model to quantify the system's performance curve during the recovery phase, and finally utilized the resilient triangle area method to quantify its resilience size. Analyzing the CTCS3-300T train control on-board system, we found that the resilience of the system with cold standby redundancy design and hot standby redundancy design were 89.44 % and 87.34 %, respectively, indicating a slight decrease in system performance after recovery from failures compared to pre-failure levels. At that time, it was necessary to adjust operational plans based on actual conditions to avoid greater impact on the railway network. This paper realizes performance resilience of train control on-board system after failure recovery, which can be applied to similar systems and provide theoretical references for realizing intelligent maintenance of the high-speed train.

Polarized vortex Smith-Purcell radiation with cascaded metasurfaces.

We introduce the concept of polarized vortex Smith-Purcell radiation by the interaction of an electron beam and cascaded metasurfaces. The spin and orbital angular momenta of Smith-Purcell radiation are determined by the cascaded metasurface that consists of a grating and a phase gradient metasurface. The grating converts the electron beam radiation into the desired polarized light, while the phase gradient metasurface generates the vortex light. Furthermore, the vortex Smith-Purcell radiation with linear and circular polarizations can be achieved by the various cascaded metasurfaces. In particular, the conversion of chirality in the Smith-Purcell radiation carrying circular polarization is accompanied by the alteration of positive and negative topological charges. This work paves the way for generating polarized vortex electron radiation and is beneficial to promote the development of free-electron-driven devices.

scDAC: deep adaptive clustering of single-cell transcriptomic data with coupled autoencoder and Dirichlet process mixture model.

MOTIVATION: Clustering analysis for single-cell RNA sequencing (scRNA-seq) data is an important step in revealing cellular heterogeneity. Many clustering methods have been proposed to discover heterogenous cell types from scRNA-seq data. However, adaptive clustering with accurate cluster number reflecting intrinsic biology nature from large-scale scRNA-seq data remains quite challenging. RESULTS: Here, we propose a single-cell Deep Adaptive Clustering (scDAC) model by coupling the Autoencoder (AE) and the Dirichlet Process Mixture Model (DPMM). By jointly optimizing the model parameters of AE and DPMM, scDAC achieves adaptive clustering with accurate cluster numbers on scRNA-seq data. We verify the performance of scDAC on five subsampled datasets with different numbers of cell types and compare it with 15 widely used clustering methods across nine scRNA-seq datasets. Our results demonstrate that scDAC can adaptively find accurate numbers of cell types or subtypes and outperforms other methods. Moreover, the performance of scDAC is robust to hyperparameter changes. AVAILABILITY AND IMPLEMENTATION: The scDAC is implemented in Python. The source code is available at https://github.com/labomics/scDAC.

Improvement of Postoperative Quality of Life in Patients Over 80 Years Old With Thoracic Spinal Stenosis.

STUDY DESIGN: A retrospective comparative study was conducted to analyze the outcome of surgical and conservative treatment for patients over 80 years old with thoracic spinal stenosis (TSS). OBJECTIVE: To evaluate the safety and efficiency of posterior spinal cord decompression surgery for over 80-year-old patients with TSS. SUMMARY OF BACKGROUND DATA: Concerned about the risk of surgery, over 80-year-old patients with TSS are usually treated conservatively, which often leads to a decline in quality of life. So far as we know, no study demonstrates the risk and benefit of spine surgery for these patients. METHODS: Over 80 years of age who underwent dorsal decompression surgery or conservative treatment due to TSS between January 2010 and November 2020 were analyzed. Sixty-four patients who completed follow-up PROM (patient-reported outcome measure) data were collected, including the mJOA (modified Japanese Orthopedic Association score) scoring system, VAS (visual analogue scale), questionnaire-based assessment of the ODI (Oswestry disability index), BI (Barthel index), and SF-36v2 (Short Form-36v2) Health Survey. The clinical characteristics, preoperative and postoperative imaging findings, operative records, complications, and individual outcomes were analyzed. RESULTS: Of the 64 patients, 38 underwent posterior decompression, pedicle screw fixation, and posterolateral fusion; another 26 chose conservative treatment. The baseline characteristics of the TSS patients in 2 groups show no significant differences. The clinical symptoms and imaging outcomes showed a significant improvement in the surgical group compared with the nonsurgical group, according to mJOA, VAS, ODI, BI, and SF-36v2. Cerebrospinal fluid leakage occurred in 6 patients, and transient neurological impairment occurred in 2 patients. CONCLUSIONS: Posterior decompression surgery for over 80-year-old patients with TSS is a safe and effective treatment, it has a good clinical outcome as well as an acceptable complication rate. However, there were no obvious improvements in quality of life or pain with conservative treatment.

Sequential treatment of concomitant odontoid fracture and lower cervical fracture-dislocation: A case report.

INTRODUCTION AND IMPORTANCE: To report the sequential treatment of a Type II odontoid fracture combined with a severe lower cervical (C6-7) fracture-dislocation featuring bilateral facet joint interlocking. CASE PRESENTATION: A 58-year-old male who had suffered an injury in a car accident, He presented neck pain and extremity paralysis. His neurological function was classified as per the American Spinal Injury Association (ASIA) impairment scale as Grade A, indicating complete deficits below the C6 spinal cord level. A cervical CT scan and magnetic resonance image showed a type II odontoid fracture, C6 slipped anteriorly, C6-7 bilateral facet joint fracture and interlocking, slightly compression change of C7 upper endplate. CLINICAL DISCUSSION: Emergency closed reduction using cranial tong traction was success 6 h after the injury. A subsequent CT scan proved the successful reduction of bilateral facet joint dislocations and the odontoid fracture. After careful overall assessment, anterior cervical decompression and fusion (ACDF) was performed at C5-6 and C6-7 segments three days later，while odontoid fracture was treated conservatively. At the 4 months follow-up, a CT scan demonstrated solid bone fusion at C5-6, C6-7 segments, along with successful healing at the odontoid fracture site. However, spinal cord was necrosis at C5-7 segments, and the patient's neurological function had no improvement. CONCLUSION: The initial closed reduction could restore the alignment and preliminary stability of cervical spine at sub-axial cervical fracture-dislocation segment as well as displaced odontoid fracture. This timely and effective closed reduction significantly diminished sequential surgical trauma and mitigated associated risks.

Kallistatin leads to cognition impairment via downregulating glutamine synthetase.

In many neurodegenerative disorders, such as Alzheimer's disease (AD), glutamate-mediated neuronal excitotoxicity is considered the basis for cognitive impairment. The mRNA and protein expression of SERPINA4(Kallistatin) are higher in patients with AD. However, whether Kallistatin plays a regulatory role in glutamate-glutamine cycle homeostasis remains unclear. In this study, we identified impaired cognitive function in Kallistatin transgenic (KAL-TG) mice. Baseline glutamate levels were elevated and miniature excitatory postsynaptic current (mEPSC) frequency was increased in the hippocampus, suggesting the impairment of glutamate homeostasis in KAL-TG mice. Mechanistically, we demonstrated that Kallistatin promoted lysine acetylation and ubiquitination of glutamine synthetase (GS) and facilitated its degradation via the proteasome pathway, thereby downregulating GS. Fenofibrate improved cognitive memory in KAL-TG mice by downregulating serum Kallistatin. Collectively, our study findings provide insights the mechanism by which Kallistatin regulates cognitive impairment, and suggest the potential of fenofibrate to prevente and treat of AD patients with high levels of Kallistatin.

Twisted photonic Weyl meta-crystals and aperiodic Fermi arc scattering.

As a milestone in the exploration of topological physics, Fermi arcs bridging Weyl points have been extensively studied. Weyl points, as are Fermi arcs, are believed to be only stable when preserving translation symmetry. However, no experimental observation of aperiodic Fermi arcs has been reported so far. Here, we continuously twist a bi-block Weyl meta-crystal and experimentally observe the twisted Fermi arc reconstruction. Although both the Weyl meta-crystals individually preserve translational symmetry, continuous twisting operation leads to the aperiodic hybridization and scattering of Fermi arcs on the interface, which is found to be determined by the singular total reflection around Weyl points. Our work unveils the aperiodic scattering of Fermi arcs and opens the door to continuously manipulating Fermi arcs.

Mosaic integration and knowledge transfer of single-cell multimodal data with MIDAS.

Integrating single-cell datasets produced by multiple omics technologies is essential for defining cellular heterogeneity. Mosaic integration, in which different datasets share only some of the measured modalities, poses major challenges, particularly regarding modality alignment and batch effect removal. Here, we present a deep probabilistic framework for the mosaic integration and knowledge transfer (MIDAS) of single-cell multimodal data. MIDAS simultaneously achieves dimensionality reduction, imputation and batch correction of mosaic data by using self-supervised modality alignment and information-theoretic latent disentanglement. We demonstrate its superiority to 19 other methods and reliability by evaluating its performance in trimodal and mosaic integration tasks. We also constructed a single-cell trimodal atlas of human peripheral blood mononuclear cells and tailored transfer learning and reciprocal reference mapping schemes to enable flexible and accurate knowledge transfer from the atlas to new data. Applications in mosaic integration, pseudotime analysis and cross-tissue knowledge transfer on bone marrow mosaic datasets demonstrate the versatility and superiority of MIDAS. MIDAS is available at https://github.com/labomics/midas .

PEDF protects retinal pigment epithelium from ferroptosis and ameliorates dry AMD-like pathology in a murine model.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision damage among elderly individuals. There is still no efficient treatment for dry AMD. Retinal pigment epithelial (RPE) degeneration has been confirmed to play an important role in dry AMD. Recent studies have reported that ferroptosis caused by iron overload and lipid peroxidation may be the primary causes of RPE degeneration. However, the upstream regulatory molecules of RPE ferroptosis remain largely unknown. Pigment epithelium-derived factor (PEDF) is an important endogenic protective factor for the RPE. Our results showed that in the murine dry AMD model induced by sodium iodate (SI), PEDF expression was downregulated. Moreover, dry AMD-like pathology was observed in PEDF-knockout mice. Therefore, the aim of this study was to reveal the effects and mechanism of PEDF on RPE ferroptosis and investigate potential therapeutic targets for dry AMD. The results of lipid peroxidation and transmission electron microscope showed that retinal ferroptosis was significantly activated in SI-treated mice and PEDF-knockout mice. Restoration of PEDF expression ameliorated SI-induced retinal dysfunction in mice, as assessed by electroretinography and optical coherence tomography. Mechanistically, western blotting and immunofluorescence analysis demonstrated that the overexpression of PEDF could upregulate the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain-1 (FTH1), which proved to inhibit lipid peroxidation and RPE ferroptosis induced by SI. This study revealed the novel role of PEDF in ferroptosis inhibition and indicated that PEDF might be a potential therapeutic target for dry AMD.

All-fiber sensor for simultaneous measurement of refractive index and temperature based on hole-assisted three-core fiber.

A hole-assisted three-core fiber (HATCF) has been proposed as a sensor for simultaneous measurement of refractive index (RI) and temperature. An 8 mm long HATCF is fused between two single mode fibers (SMFs). One air hole of the HATCF is opened by femtosecond laser ablation technique to expose a suspended core to the external environment. Due to the same diameters of the two suspended cores, the resonance couplings between the center core and the two suspended cores occur at the same wavelength, which leads to a strong resonance dip. When the solution is filled into the open air hole, the resonance dip is split in two dips because the phase matching wavelength between center core and the suspended core in the open air hole is changed. Simultaneous measurement of RI and temperature can be achieved by monitoring the wavelengths of the two dips. The measured RI and temperature sensitivities are 1369 nm/RIU in the range of 1.333-1.388 and 83.48 pm/°C in the range of 25-70 °C. The proposed sensor has outstanding advantages such as simple structure, high integration and dual parameter measurement, making it a potential application in the field of biological detection.

Simultaneous measurement of temperature and salinity based on a hole-assisted dual-core fiber.

An optical fiber sensor based on a hole-assisted dual-core fiber (HADCF) has been proposed and experimentally demonstrated for dual-parameter measurements. The dual-mode interferometer created uses the LP01 mode and LP11 mode in the suspended core of a specialist optical fiber, combined with a directional coupler formed by using the suspended core and the center core in a 16 mm long HADCF. Using this, the simultaneous measurement of salinity (due to the presence of NaCl) and temperature has been achieved through monitoring the interference dip and resonance dip. The sensitivities of the measurement of salinity and temperature are 190.7 pm/‰ and -188.2 pm/°C, respectively. The sensor developed has the advantages of simplicity of fabrication, a high level of integration and the potential for measurement of dual parameters, supporting its potential applications in marine environment measurements.

Diverse ranking metamaterial inverse design based on contrastive and transfer learning.

Metamaterials, thoughtfully designed, have demonstrated remarkable success in the manipulation of electromagnetic waves. More recently, deep learning can advance the performance in the field of metamaterial inverse design. However, existing inverse design methods based on deep learning often overlook potential trade-offs of optimal design and outcome diversity. To address this issue, in this work we introduce contrastive learning to implement a simple but effective global ranking inverse design framework. Viewing inverse design as spectrum-guided ranking of the candidate structures, our method creates a resemblance relationship of the optical response and metamaterials, enabling the prediction of diverse structures of metamaterials based on the global ranking. Furthermore, we have combined transfer learning to enrich our framework, not limited in prediction of single metamaterial representation. Our work can offer inverse design evaluation and diverse outcomes. The proposed method may shrink the gap between flexibility and accuracy of on-demand design.

Phase noise suppression technique based on an improved reference interferometer scheme.

The reference interferometer scheme is an effective noise reduction method, but the optical path length difference (OPD) of the two interferometers must be strictly equal, which limits its application in practical environments. In this paper, an improved reference interferometer demodulation technique without strictly equal OPDs is proposed to suppress phase noise. By introducing a reference interferometer, the phase noise can be removed from the demodulation results. The combination of the differential self-multiplication algorithm and the fitted phase modulation depth calculation formula can evaluate the phase modulation depth of both interferometers in real time and simultaneously eliminate the nonlinear distortion caused by phase modulation depth drift and the effect of different OPDs on the reference interferometer scheme. The experimental results show that the technique can obtain highly stable and accurate demodulation results even if the OPDs of the two reference interferometers are different. The phase modulation depth calculation error is less than 0.57%, the maximum phase noise reduction is 15 dB, the average reduction is 9 dB, the minimum total harmonic distortion is 0.17%, and the SINAD reaches 35.90 dB.

High-resolution compact spectrometer based on periodic tapered coreless fiber.

This Letter proposes a method that balances miniaturization and high performance of fiber optic speckle spectrometers. The periodically tapered coreless fiber is used as the scattering element to excite more higher-order modes in the coreless fiber. As a result, a remarkable spectral resolution of 0.03 nm in the near-infrared spectrum can be achieved with a 5-cm-long fiber. Narrow linewidth and broadband spectra in the wavelength of 1540-1560 nm are reconstructed separately, demonstrating the excellent performance of the designed all-fiber spectrometer. The spectral resolution of our proposed spectrometer is comparable to that of a 2-m multimode fiber spectrometer and has a significant improvement in miniaturization.

Improved topography measurement with a high dynamic range using phase difference sensing technology.

Phase difference sensing technology (PDST) is employed for topography measurement, and two interference structures are proposed to achieve upper-limit adjustment and high resolution in the measurement range: a dual-wavelength system with a single Fabry-Perot (FP) cavity and a single-wavelength system with dual FP cavities. The phase difference between the two interference signals is determined by an elliptic fitting algorithm (EFA), and this change in phase difference is utilized to characterize the step height. Experimental results indicate that the measurement upper-limit can be adjusted to either 410 µm, 187 µm, or 108 µm by varying the wavelength difference in the dual-wavelength system, which gives a measurement error of 2.96%. In contrast, while offering a measurement resolution of 3.47 nm, the single-wavelength system exhibits a measurement error of 5.38%. The proposed method is capable of satisfying the measurement requirements during micro-electromechanical system (MEMS) processing with proficiency.

Cytomodulin-10 modified GelMA hydrogel with kartogenin for in-situ osteochondral regeneration.

The incidence of osteochondral defect is increasing year by year, but there is still no widely accepted method for repairing the defect. Hydrogels loaded with bioactive molecules have provided promising alternatives for in-situ osteochondral regeneration. Kartogenin (KGN) is an effective and steady small molecule with the function of cartilage regeneration and protection which can be further boosted by TGF-ß. However, the high cost, instability, and immunogenicity of TGF-ß would limit its combined effect with KGN in clinical application. In this study, a composite hydrogel CM-KGN@GelMA, which contained TGF-ß1 analog short peptide cytomodulin-10 (CM-10) and KGN, was fabricated. The results indicated that CM-10 modified on GelMA hydrogels exerted an equivalent role in enhancing chondrogenesis as TGF-ß1, and this effect was also boosted when combined with KGN. Moreover, it was revealed that CM-10 and KGN had a synergistic effect on promoting the chondrogenesis of BMSCs by up-regulating the expression of RUNX1 and SOX9 at both mRNA and protein levels in vitro. Finally, the composite hydrogel exhibited a satisfactory osteochondral defect repair effect in vivo, showing similar structures close to the native tissue. Taken together, this study has revealed that CM-10 may serve as an alternative for TGF-ß1 and can collaborate with KGN to accelerate chondrogenesis, which suggests that the fabricated CM-KGN@GelMA composite hydrogel can be acted as a potential scaffold for osteochondral defect regeneration. STATEMENT OF SIGNIFICANCE: Kartogenin and TGF-ß have shown great value in promoting osteochondral defect regeneration, and their combined application can enhance the effect and show great potential for clinical application. Herein, a functional CM-KGN@GelMA hydrogel was fabricated, which was composed of TGF-ß1 mimicking peptide CM-10 and KGN. CM-10 in hydrogel retained an activity like TGF-ß1 to facilitate BMSC chondrogenesis and exhibited boosting chondrogenesis by up-regulating RUNX1 and SOX9 when being co-applied with KGN. In vivo, the hydrogel promoted cartilage regeneration and subchondral bone reconstruction, showing similar structures as the native tissue, which might be vital in recovering the bio-function of cartilage. Thus, this study developed an effective scaffold and provided a promising way for osteochondral defect repair.

Licochalcone A Derivatives as Selective Dipeptidyl Peptidase 4 Inhibitors with Anti-Inflammatory Effects.

A set of 22 analogs of licochalcone A was designed and synthesized to explore their potentials as dipeptidyl peptidase 4 (DPP4) inhibitors with anti-inflammatory effects. The anti-DPP4 effects of these analogs were evaluated using the fluorescent substrate Gly-Pro-N-butyl-4-amino-1,8-naphthalimide (GP-BAN). The nitro-substituted analogue 27 exhibited the most potent activity (Ki = 0.96 µM). A structure-activity relationship investigation revealed that 4-hydroxyl and 5-chloro substituents are essential for DPP4 inhibition, while the 3'-nitro substituent improved both DPP4 inhibition and microsomal stability. Furthermore, compound 27 demonstrated good selectivity for DPP4 over other proteases, including dipeptidyl peptidase 9 (DPP9), thrombin, prolyl endopeptidase (PREP), and fibroblast activation protein (FAP). The cytotoxic effect of 27 was evaluated in cancer cell lines HepG-2 and Caco-2 and in somatic RAW264.7 cells and RPTECs. Compound 27 showed no toxicity to normal cells and weak toxicity to cancer cells. In a living cell imaging assay, 27 blocked the dipeptidase activity of DPP4 in both Caco-2 and HepG-2 cells. This compound also dose-dependently suppressed the expression levels of the chemokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß).

Discovery of 4'-trifluoromethylchalcones as novel, potent and selective hCYP1B1 inhibitors without concomitant AhR activation.

Human cytochrome P450 1B1 (hCYP1B1), an extrahepatic cytochrome P450 enzyme over-expressed in various tumors, has been validated as a promising target for preventing and treating cancers. Herein, two series of chalcone derivatives were synthesized to discover potent hCYP1B1 inhibitors without AhR agonist effect. Structure-activity relationship (SAR) studies demonstrated that 4'-trifluoromethyl on the B-ring strongly enhanced the anti-hCYP1B1 effects, identifying A9 as a promising lead compound. Further SAR analysis on A9 derivatives (modified A-ring of 4'-trifluoromethylchalcone) showed that introducing 2-methoxyl improved the anti-hCYP1B1 effect and selectivity, while introducing a methoxyl at the C-4 site was beneficial for avoiding AhR activation. Ultimately, five 4'-trifluoromethyl chalcones were identified as potent hCYP1B1 inhibitors (IC50 < 10 nM), while B18 exhibits the most potent anti-hCYP1B1 effect (IC50 = 3.6 nM), suitable metabolic stability and good cell-permeability. B18 also acted as an AhR antagonist and could down-regulate hCYP1B1 in living systems. Mechanistic studies showed that B18 potently inhibited hCYP1B1 in a competitive inhibition manner (Ki = 3.92 nM), while docking simulations revealed that B18 could tightly bind to the catalytic cavity of hCYP1B1 mainly via hydrophobic and hydrogen-bonding interactions. Furthermore, B18 could potently inhibit hCYP1B1 in living cells and showed remarkable anti-migration ability on MFC-7 cells. Taken together, this study deciphered the SARs of chalcones as hCYP1B1 inhibitors and provided several potent hCYP1B1 inhibitors as promising candidates for the development of more efficacious anti-migration agents.

Improved ellipse-fitting phase demodulation technique to suppress the effect of light source intensity noise in interferometric system.

An improved ellipse-fitting algorithm phase demodulation (EFAPD) technique is proposed to reduce the influence of light source intensity noise on a system. In the original EFAPD, the sum of the intensities of coherent light (ICLS) is an important part of the interference signal noise, which makes the demodulation results suffer. The improved EFAPD corrects the ICLS and fringe contrast quantity of the interference signal by an ellipse-fitting algorithm, and then calculates the ICLS based on the structure of pull-cone 3 × 3 coupler, so as to remove it in the algorithm. Experimental results show that the noise of the improved EFAPD system is significantly reduced compared with that of the original EFAPD, with a maximum reduction of 35.57 dB. The improved EFAPD makes up for the deficiency of the original EFAPD in suppressing light source intensity noise, and promotes the application and popularization of EFAPD.

Annular and unidirectional transverse scattering with high directivity based on magnetoelectric coupling.

Transverse scattering is a special directional scattering perpendicular to the propagation direction, which has attracted great interest due to its potential applications from directional antennas, optical metrology to optical sensing. Here we reveal annular transverse scattering and unidirectional transverse scattering by magnetoelectric coupling of Omega particle. The annular transverse scattering can be achieved by the longitudinal dipole mode of the Omega particle. Furthermore, we demonstrate the highly asymmetric unidirectional transverse scattering by adjusting the transverse electric dipole (ED) and longitudinal magnetic dipole (MD) modes. Meanwhile, the forward scattering and backward scattering are suppressed by the interference of transverse ED and longitudinal MD modes. In particular, the lateral force exerted on the particle is accompanied by the transverse scattering. Our results provide a useful toolset for manipulating light scattered by the particle and broaden the application range of the particle with magnetoelectric coupling.