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.

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.

Enhanced intrinsic chiroptical response of resonant metallic metasurfaces.

The physics of resonant metasurfaces underpins many electromagnetic functionalities with enhanced performance by virtue of resonant excitations. Resonances originating from bound states in the continuum (BICs) were recently recognized in photonics for their superior optical properties, strong local field enhancement, and suppression of radiative losses. Very recently, a concept of intrinsically chiral dielectric BIC metasurfaces was proposed that combines strong narrowband resonant features with the polarization control of scattered light. Here, we design a resonant chiral metallic metasurface supporting a BIC resonance in the microwave wavelength range. In our structure, the metasurface units (meta-atoms) are characterized with rotational and mirror spatial symmetries. We numerically characterize metasurface mode properties in eigenmode calculations and scattering spectra for linearly polarized excitation under oblique incidence. Then, we investigate intrinsic chiroptical effects for transmission of normally propagating excitation beams by breaking the meta-atom in-plane mirror symmetries. We predict that the intrinsic circular dichroism in such structures may exceed 0.74.

Stably suppressing laser relative intensity noise on a 3 × 3 coupler interferometric system.

A 3 × 3 coupler multiphase demodulation scheme is proposed to eliminate the impact of working point drifting and the laser relative intensity noise (RIN) on a 3 × 3 coupler interferometric system. An ellipse-fitting algorithm (EFA) is applied to fit the two interference signals of the 3 × 3 coupler in order, then the ATAN algorithm is applied to obtain three noise-containing signals with specific trigonometric relationships. By averaging the three signals, the demodulated phase noise induced from RIN can be effectively eliminated. The experimental results show that compared with the asymmetric demodulation scheme without intensity noise control, the noise floor of the proposed scheme decreases from 4.5 to 1 µrad/√Hz at 1 kHz and 2.7 to 0.8 µrad/√Hz at 3 kHz. At high frequencies, the average noise floor level is reduced from 10 to 0.9 µrad/√Hz, a reduction of about 21 dB. Furthermore, the variation range of the average noise floor is reduced from 5.4 to 0.17 µrad /√Hz within 100 s.

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.

Rational Construction of a Novel Bioluminescent Substrate for Sensing the Tumor-Associated Hydrolase Notum.

Notum, one of the key serine hydrolases in mammals, hydrolyzes the palmitoleoyl moieties of many important proteins and modulates multiple signaling pathways including Wnt/ß-catenin signaling. Notum is tightly associated with multiple human diseases, but the reliable and practical tools for sensing Notum activities in complex biological systems are rarely reported. Herein, an efficient strategy was used to rationally construct a specific bioluminescent substrate for Notum. Following computer-aided molecular design and experimental verification, octanoyl luciferin (OL) was selected as the optimum substrate for human Notum, with excellent specificity, high detection sensitivity and high signal-to-noise ratio. Under physiological conditions, OL was readily hydrolyzed by Notum or Notum-containing biological specimens to release d-luciferin that could be easily detected by various fluorescence devices in the presence of luciferase. The applicability of OL for real-time sensing native Notum was examined in living cells, extracellular matrix, and tissue preparations. OL was also used for constructing a high-throughput assay for screening of Notum inhibitors, while a natural compound (bergapten) was newly identified as a potent Notum inhibitor. Collectively, this study devises a reliable and easy-to-use tool for sensing Notum activities in biological systems, which will strongly facilitate hNotum-associated fundamental studies, disease diagnosis, and drug discovery.

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.

Bifunctional sensing based on an exceptional point with bilayer metasurfaces.

Exceptional points (EPs), the critical phase transition points of non-Hermitian parity-time (PT) systems, exhibit many novel physical properties and associated applications, such as ultra-sensitive detection of perturbations. Here, a bilayer metasurface with two orthogonally oriented split-ring resonators (SRRs) is proposed and a phase transition of the eigenpolarization states is introduced via changing the conductivity of vanadium dioxide (VO2) patch integrated into the gap of one SRR. The metasurface possesses a passive PT symmetry and an EP in polarization space is observed at a certain conductivity of the VO2. Two sensing schemes with the metasurface are proposed to achieve high-sensitivity sensing of temperature and refractive index in the terahertz (THz) range. The metasurface is promising for applications in THz biosensing and polarization manipulation.

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.

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.

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.

Ameliorated PGC demodulation technique based on the ODR algorithm with insensitivity to phase modulation depth.

For the optical fiber sensing system using phase generated carrier (PGC) technology, it is very important to eliminate the nonlinear effect of phase modulation depth (C) fluctuation on the demodulation results in the actual environment. In this paper, an ameliorated phase generated carrier demodulation technique is presented to calculate the C value and suppress its nonlinear influence on the demodulation results. The value of C is calculated out by the fundamental and third harmonic components with the equation fitted by the orthogonal distance regression algorithm. Then the Bessel recursive formula is used to convert the coefficients of each order of Bessel function contained in demodulation result into C values. Finally, the coefficients in demodulation result are removed by the calculated C values. In the experiment, when the C ranges from 1.0 rad to 3.5 rad, the minimum total harmonic distortion and maximum phase amplitude fluctuation of the ameliorated algorithm are 0.09% and 3.58%, which are far superior to the demodulation results of the traditional arctangent algorithm. The experimental results demonstrate that the proposed method can effectively eliminate the error caused by the fluctuation of the C value, which provides a reference for signal processing in practical applications of fiber-optic interferometric sensors.

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.

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.

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.

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).

Tunable circular polarization responses of twisted black phosphorus metamaterials.

As one of the most significant 2D materials, black phosphorus (BP) offers a promising way to manipulate the polarization state of light due to its in-plane anisotropy, however, reconfigurable polarization manipulation is still challenging in simple BP structure. Here, we propose a multilayer metamaterial with twisted BP nanostructures and numerically study its circular dichroism (CD) and circular birefringence (CB) responses. The dependences of the circular polarization responses in the twisted BP metamaterial have been fully investigated on geometrical and material parameters. The giant tunability enables the twisted BP nanostructure to be attractive for constructing BP-based metamaterials devices, such as polarizers, biosensors and modulators.

Dual-channel refractive index sensor based on coupling between LP01 and LP11 modes in the tapered hole-assisted dual-core fiber.

We propose a refractive index (RI) sensor based on a tapered hole-assisted dual-core fiber (HADCF). The sensor is fabricated by splicing a tapered HADCF between two single-mode fibers and operates on the coupling between the fundamental mode and the low-order mode in two cores. The HADCF is tapered to meet the phase matching condition between the fundamental mode (LP01) in the central core and the low-order mode (LP11) in the eccentric core. The tapered waist of the fiber becomes thinner; the coupling wavelength has a blue shift. Glycerin solutions of different RIs were injected into the air hole. The RI sensitivity of 936.69 nm/RIU is obtained in the RI range of 1.335-1.360. The multi-channel RI sensor cascaded by HADCFs with different taper lengths is obtained and can simultaneously measure the RI of different solutions. The proposed device has the advantages of high sensitivity, simple structure, and stable performance. The special microfluidic channel in the HADCF can protect the tested solution from external environmental pollution.

VO2-enabled transmission-reflection switchable coding terahertz metamaterials.

Coding metamaterials have offered unprecedented degrees of freedom to manipulate electromagnetic waves in time and frequency domains in terms of various coding sequences, however, it is still challenging to realize dynamic coding metamaterials in the terahertz range. Here, we propose VO2-enabled transmission-reflection switchable coding terahertz metamaterials consisting of multilayered gold and VO2 patterns. The insulator-to-metal transition of VO2 leads to switch between the refractive and reflective scattering beams by changing the temperature. The four 2-bit elements are used to construct coding metasurface-based OAM generator with l = 1. Remarkably, the transmission-reflection switching functionality of the coding metasurface can be achieved at different frequencies. In addition, the novel designs in our work can achieve EM waves manipulation and provide a useful method to dynamically switch transmission-reflection response in the THz frequency regime.