SSNMDI: a novel joint learning model of semi-supervised non-negative matrix factorization and data imputation for clustering of single-cell RNA-seq data.

MOTIVATION: Single-cell RNA sequencing (scRNA-seq) technology attracts extensive attention in the biomedical field. It can be used to measure gene expression and analyze the transcriptome at the single-cell level, enabling the identification of cell types based on unsupervised clustering. Data imputation and dimension reduction are conducted before clustering because scRNA-seq has a high 'dropout' rate, noise and linear inseparability. However, independence of dimension reduction, imputation and clustering cannot fully characterize the pattern of the scRNA-seq data, resulting in poor clustering performance. Herein, we propose a novel and accurate algorithm, SSNMDI, that utilizes a joint learning approach to simultaneously perform imputation, dimensionality reduction and cell clustering in a non-negative matrix factorization (NMF) framework. In addition, we integrate the cell annotation as prior information, then transform the joint learning into a semi-supervised NMF model. Through experiments on 14 datasets, we demonstrate that SSNMDI has a faster convergence speed, better dimensionality reduction performance and a more accurate cell clustering performance than previous methods, providing an accurate and robust strategy for analyzing scRNA-seq data. Biological analysis are also conducted to validate the biological significance of our method, including pseudotime analysis, gene ontology and survival analysis. We believe that we are among the first to introduce imputation, partial label information, dimension reduction and clustering to the single-cell field. AVAILABILITY AND IMPLEMENTATION: The source code for SSNMDI is available at https://github.com/yushanqiu/SSNMDI.

Nonfrontal Control of Working Memory.

Items held in visual working memory can be quickly updated, replaced, removed, and even manipulated in accordance with current behavioral goals. Here, we use multivariate pattern analyses to identify the patterns of neuronal activity that realize the executive control processes supervising these flexible stores. We find that portions of the middle temporal gyrus and the intraparietal sulcus represent what item is cued for continued memorization independently of representations of the item itself. Importantly, this selection-specific activity could not be explained by sensory representations of the cue and is only present when control is exerted. Our results suggest that the selection of memorized items might be controlled in a distributed and decentralized fashion. This evidence provides an alternative perspective to the notion of "domain general" central executive control over memory function.

Multidimensional Widefield Infrared-Encoded Spontaneous Emission Microscopy: Distinguishing Chromophores by Ultrashort Infrared Pulses.

Photoluminescence (PL) imaging has broad applications in visualizing biological activities, detecting chemical species, and characterizing materials. However, the chemical information encoded in the PL images is often limited by the overlapping emission spectra of chromophores. Here, we report a PL microscopy based on the nonlinear interactions between mid-infrared and visible excitations on matters, which we termed MultiDimensional Widefield Infrared-encoded Spontaneous Emission (MD-WISE) microscopy. MD-WISE microscopy can distinguish chromophores that possess nearly identical emission spectra via conditions in a multidimensional space formed by three independent variables: the temporal delay between the infrared and the visible pulses (t), the wavelength of visible pulses (λvis), and the frequencies of the infrared pulses (ωIR). This method is enabled by two mechanisms: (1) modulating the optical absorption cross sections of molecular dyes by exciting specific vibrational functional groups and (2) reducing the PL quantum yield of semiconductor nanocrystals, which was achieved through strong field ionization of excitons. Importantly, MD-WISE microscopy operates under widefield imaging conditions with a field of view of tens of microns, other than the confocal configuration adopted by most nonlinear optical microscopies, which require focusing the optical beams tightly. By demonstrating the capacity of registering multidimensional information into PL images, MD-WISE microscopy has the potential of expanding the number of species and processes that can be simultaneously tracked in high-speed widefield imaging applications.

Autophagy core protein BECN1 is vital for spermatogenesis and male fertility in mice†.

Mammalian spermatogenesis is a highly complex multi-step biological process, and autophagy has been demonstrated to be involved in the process of spermatogenesis. Beclin-1/BECN1, a core autophagy factor, plays a critical role in many biological processes and diseases. However, its function in spermatogenesis remains largely unclear. In the present study, germ cell-specific Beclin 1 (Becn1) knockout mice were generated and were conducted to determine the role of Becn1 in spermatogenesis and fertility of mice. Results indicate that Becn1 deficiency leads to reduced sperm motility and quantity, partial failure of spermiation, actin network disruption, excessive residual cytoplasm, acrosome malformation, and aberrant mitochondrial accumulation of sperm, ultimately resulting in reduced fertility in male mice. Furthermore, inhibition of autophagy was observed in the testes of germ cell-specific Becn1 knockout mice, which may contribute to impaired spermiogenesis and reduced fertility. Collectively, our results reveal that Becn1 is essential for fertility and spermiogenesis in mice.

4-(Triethoxysilyl)butanoic acid as a self-assembled monolayer for surface modification of titanium dioxide.

In this study, the carboxy silane 4-(triethoxysilyl)butanoic acid (TESBA) was used to modify titanium dioxide (TiO2) to create a self-assembled monolayer (SAM) and then directionally immobilize a capture antibody using protein A. We selected the amino silane (3-aminopropyl)triethoxysilane (APTES) to perform a comparative analysis with TESBA, and employed glutaraldehyde (GA) as the control. The modification and detection effects and the limit of detection (LOD) were evaluated by detecting human immunoglobulin G (IgG). The average normalized sensitivity of the dual-grating coupler waveguide biosensor was 49.63 ± 0.27 RIU-1 and the optimum resolution was 1.30 × 10-6 RIU. When the SAM was prepared using TESBA and APTES followed by GA, the LOD was 4.59 × 10-7 g mL-1 and 5.29 × 10-7 g mL-1, respectively. We analyzed the modification and detection effects by the t-test and concluded that the differences in the modification effects using TESBA and APTES followed by GA were significant and the differences in the detection effects using TESBA and APTES followed by GA were insignificant. The use of TESBA as the SAM led to the modification effect being superior to that obtained using APTES followed by GA. The detection effect using TESBA was as outstanding as that using APTES followed by GA. Our findings demonstrate the feasibility and effectiveness of using TESBA as the SAM to carboxylate the surface of TiO2, thereby enabling immobilization of biomolecules for human IgG detection.

Boosted charge separation via Ce2S3 over dual Z-scheme ZnO-Ce2S3-MnO2 core double-shell nanocomposite for the degradation of diverse dye pollutants.

Herein, core double-shell direct dual Z-scheme ZnO-Ce2S3-MnO2 nanocomposite was synthesized via a hydrothermal route along with pure ZnO, Ce2S3, MnO2, and characterized by numerous characterization tools for application in synthetic dyes degradation. The XRD, Raman, and FTIR analyses have confirmed the nanocomposite formation. TEM images exhibited the core double-shell morphology with an average particle diameter of 81 nm and stacking of ZnO, Ce2S3, and MnO2. EDX confirmed the existence of desired elements in the grown composition. The varied oxidation states, presence of defects, and fast charge transfer were also revealed from XPS, PL, and EIS. The ZnO-Ce2S3-MnO2 nanocomposite has an optical energy bandgap of 2.84 eV, capable of decomposing harmful dyes with excellent efficiency, 99.81% MB, 97.62% MO, 88.5% MR, and 58.9% EY in 40 min sunlight exposure. The effect of several operating parameters is also observed and obtained results showed the optimal catalyst dose was 20 mg, pH of 8, and dye concentration of 10 ppm. The scavenger's experiment suggests that •O2- and •OH are the main active radicals in the photodegradation reaction which is also evident in the dual Z-scheme formation. The MnO2 and ZnO layers covered the Ce2S3 (core) and dual Z-scheme formation allows rapid kinetics of redox reaction and provides plenteous channels for transfer of photo-generated charge carriers during photocatalysis. Thus, core double-shell direct dual Z-scheme photocatalysts having inorganic components could be an excellent choice for photocatalysis at the industrial level, particularly for water purification.

Categorical working memory codes in human visual cortex.

Working memory contents are represented in neural activity patterns across multiple regions of the cortical hierarchy. A division of labor has been proposed where more anterior regions harbor increasingly abstract and categorical representations while the most detailed representations are held in primary sensory cortices. Here, using fMRI and multivariate encoding modeling, we demonstrate that for color stimuli categorical codes are already present at the level of extrastriate visual cortex (V4 and VO1), even when subjects are neither implicitly nor explicitly encouraged to categorize the stimuli. Importantly, this categorical coding was observed during working memory, but not during perception. Thus, visual working memory is likely to rely at least in part on categorical representations. SIGNIFICANCE STATEMENT: Working memory is the representational basis for human cognition. Recent work has demonstrated that numerous regions across the human brain can represent the contents of working memory. We use fMRI brain scanning and machine learning methods to demonstrate that different regions can represent the same content differently during working memory. Reading out the neural codes used to store working memory contents, we show that already in sensory cortex, areas V4 and VO1 represent color in a categorical format rather than a purely sensory fashion. Thereby, we provide a better understanding of how different regions of the brain might serve working memory and cognition.

Rational Design of Asymmetric Polymethines to Attain NIR(II) Bioimaging at >1100 nm.

Organic molecules having emission in the NIR(II) region are emergent and receiving enormous attention. Unfortunately, attaining accountable organic emission intensity around the NIR(II) region is hampered by the dominant internal conversion operated by the energy gap law, where the emission energy gap and the associated internal reorganization energy λint play key roles. Up to the current stage, the majority of the reported organic NIR(II) emitters belong to those polymethines terminated by two symmetric chromophores. Such a design has proved to have a small λint that greatly suppresses the internal conversion. However, the imposition of symmetric chromophores is stringent, limiting further development of organic NIR(II) dyes in diversity and versatility. Here, we propose a new concept where as far as the emissive state of the any asymmetric polymethines contains more or less equally transition density between two terminated chromophores, λint can be as small as that of the symmetric polymethines. To prove the concept, we synthesize a series of new polymethines terminated by xanthen-9-yl-benzoic acid and 2,4-diphenylthiopyrylium derivatives, yielding AJBF1112 and AEBF1119 that reveal emission peak wavelength at 1112 and 1119 nm, respectively. The quantum yield is higher than all synthesized symmetric polymethines of 2,4-diphenylthiopyrylium derivatives (SC1162, 1182, 1185, and 1230) in this study. λint were calculated to be as small as 6.2 and 7.3 kcal/mol for AJBF1112 and AEBF1119, respectively, proving the concept. AEBF1119 was further prepared as a polymer dot to demonstrate its in vitro specific cellular imaging and in vivo tumor/bone targeting in the NIR(II) region.

Mid-infrared silicon metasurfaces for near-field enhancement of molecular fingerprints.

Mid-infrared dielectric metasurfaces are promising fundamental building blocks for integrated sensing with high sensitivity, compositional selectivity, and low loss. We have designed and fabricated a silicon metasurface with resonance properties in the 4∼5 µm mid-infrared region and a volume enhancement of up to 9 times. Benchmark FTIR characterizations of solutions of tungsten hexacarbonyl molecules showed a detection limit of 1 mg/mL without the usage of surface enrichment treatment. We further rationalize the detection limit of the molecules-nanostructure open interface with volume field enhancement analysis. Our results show that mid-infrared silicon metasurfaces may be a suitable platform for potential integration with microfluidic for in vivo detection.

Photocatalytic microbial disinfection under indoor conditions: Prospects and challenges of near IR-photoactive materials.

The accumulation of microbes especially in the air and in water bodies is causing the major disease outbreaks. Indoor environment remediation methods are necessary today to clean up these microbes. Among the remediation methods available, in situ generation of highly reactive and oxidizing radical species by advanced oxidation processes (AOPs) inactivate most of the microbes unselectively. Of these AOPs, photocatalytic microbial disinfection especially under indoor conditions is of great interest to maintain microbe-free indoor environment. For efficient microbes' inactivation under indoor conditions, the near IR and IR response of the photocatalysts must be improved. Though the photocatalytic disinfection of microbes using semiconductor-based photocatalysts has been extensively investigated, most of the photocatalysts that have been investigated are either weekly responsive or totally not irresponsive to IR photons due to inappropriate bandgap energies. Several strategies have been investigated to enhance the light harvesting properties of semiconductor based photocatalysts under indoor conditions and make them active to near IR and IR radiations. This review summarizes the recent progress in the field of materials for photocatalysts employed for microbial removal in indoor environments over the past decade as well as outlines key perspectives to enlighten future researches. The paper details the fundamentals of photocatalysis and basic properties of photocatalytic materials in the disinfection of common microbes under indoor conditions. The applications of photocatalytic materials in the disinfection of microbes in indoor environmental conditions are discussed and reviewed. Finally, the remaining challenges and future strategies/prospects in the design and synthesis of IR (and near IR) responsive photocatalysts are discussed.

Cell Membrane Biomimetic Nanoparticles with Potential in Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is to blame for about 60% of dementia cases worldwide. The blood-brain barrier (BBB) prevents many medications for AD from having clinical therapeutic effects that can be used to treat the affected area. Many researchers have turned their attention to cell membrane biomimetic nanoparticles (NPs) to solve this situation. Among them, NPs can extend the half-life of drugs in the body as the "core" of the wrapped drug, and the cell membrane acts as the "shell" of the wrapped NPs to functionalize the NPs, which can further improve the delivery efficiency of nano-drug delivery systems. Researchers are learning that cell membrane biomimetic NPs can circumvent the BBB's restriction, prevent harm to the body's immune system, extend the period that NPs spend in circulation, and have good biocompatibility and cytotoxicity, which increases efficacy of drug release. This review summarized the detailed production process and features of core NPs and further introduced the extraction methods of cell membrane and fusion methods of cell membrane biomimetic NPs. In addition, the targeting peptides for modifying biomimetic NPs to target the BBB to demonstrate the broad prospects of cell membrane biomimetic NPs drug delivery systems were summarized.

Large-Grain Spanning Monolayer Cu2 ZnSnSe4 Thin-Film Solar Cells Grown from Metal Precursor.

The persistent double layer structure whereby two layers with different properties form at the front and rear of absorbers is a critical challenge in the field of kesterite thin-film solar cells, which imposes additional nonradiative recombination in the quasi-neutral region and potential limitation to the transport of hole carriers. Herein, an effective model for growing monolayer CZTSe thin-films based on metal precursors with large grains spanning the whole film is developed. Voids and fine grain layer are avoided successfully by suppressing the formation of a Sn-rich liquid metal phase near Mo back contact during alloying, while grain coarsening is greatly promoted by enhancing mass transfer during grain growth. The desired morphology exhibits several encouraging features, including significantly reduced recombination in the quasi-neutral region that contributes to the large increase of short-circuit current, and a quasi-Ohmic back contact which is a prerequisite for high fill factor. Though this growth mode may introduce more interfacial defects which require further modification, the strategies demonstrated remove a primary obstacle toward higher efficiency kesterite solar cells, and can be applicable to morphology control with other emerging chalcogenide thin films.

10.3% Efficient Green Cd-Free Cu2 ZnSnS4 Solar Cells Enabled by Liquid-Phase Promoted Grain Growth.

Small grain size and near-horizontal grain boundaries are known to be detrimental to the carrier collection efficiency and device performance of pure-sulfide Cu2 ZnSnS4 (CZTS) solar cells. However, forming large grains spanning the absorber layer while maintaining high electronic quality is challenging particularly for pure sulfide CZTS. Herein, a liquid-phase-assisted grain growth (LGG) model that enables the formation of large grains spanning across the CZTS absorber without compromising the electronic quality is demonstrated. By introducing a Ge-alloyed CZTS nanoparticle layer at the bottom of the sputtered precursor, a Cu-rich and Sn-rich liquid phase forms at the high temperature sulfurization stage, which can effectively remove the detrimental near-horizontal grain boundaries and promote grain growth, thus greatly improving the carrier collection efficiency and reducing nonradiative recombination. The remaining liquid phase layer at the rear interface shows a high work function, acting as an effective hole transport layer. The modified morphology greatly increases the short-circuit current density and fill factor, enabling 10.3% efficient green Cd-free CZTS devices. This work unlocks a grain growth mechanism, advancing the morphology control of sulfide-based kesterite solar cells.

Visible transparent mid-infrared broadband absorbers based on gradient refractive indexes and multi-size cavity resonances.

We proposed a multi-layered nanorod structure with the same tilt angle and different diameters, which has high visible transmittance and strong 3-5 µm absorption based on the principles of the gradient of the refractive index and the multi-size cavity resonances. The indium tin oxide (ITO) was selected as the target material to fabricate the structure by using a glancing angle deposition method. The experimental results show that when the deposition angle θ is 80°, swing deposition is successively done with the rotation angle φ of ±8°, ± 5°, ± 3°, and 0° on the surface of the substrate, and the quartz crystal microbalance thicknesses of ITO nanorods are 220 nm for each deposition, the average transmittance is 80.5% in the range of 400-800 nm and the integrated absorption is 86% in the 3-5 µm band. Such a simple, low-cost, and easy-to-fabricate device has potential applications in window stealth materials and other related fields.

3-5 µm mid-infrared broadband absorbers composed of layered ITO nanorod arrays with high visible light transmittance.

A mid-infrared broadband absorber with high visible light transmittance is proposed in this paper. The absorber is composed of layered ITO nanorod arrays with increasing angles fabricated by oblique angle deposition technique. The experimental results show that the average transmittance of the absorber reaches 80% in the 400-800 nm band and the integrated absorption reaches 82.9% in the 3-5 µm band, when the QCM thickness of the first layer of film is 100 nm and the deposition angle θ is 10°, the QCM heights of the second to fifth layers of nanorods are all 330 nm, and their deposition angles are 55°, 68°, 80°, and 87°, respectively. The high transmittance in the visible band is attributed to the gradient of the refractive index. The broadband absorption in the mid-infrared band results from different resonances in the empty cavities with different sizes. Such a simple and large-area absorber has potential applications in window materials and infrared cloaking.

ITO/Si/ITO semi-cone-shell chiral complexes on silicon nanocones with broadband circular dichroism in the mid-infrared wavelength.

This paper proposed ITO/Si/ITO semi-cone-shell chiral complexes on silicon nanocones with broadband CD in the mid-infrared band. The experimental results show that when the deposition angle θ = 45°, the first ITO deposition of ta = 100 nm, the second Si deposition of tb = 200 nm with the azimuth angle unchanged, and the third ITO deposition of tc = 200 nm after rotating the azimuth angle of 60°, the prepared chiral structure has a broadband CD response in the mid-infrared band of 2.5-4 µm. The broadband CD effect is produced by the internal resonance of the three-dimensional open cavity. The cone structure can be regarded as a plurality of planar open resonant rings with different diameters, and these rings resonate at different wavelengths. The experimental results also show that the proposed chiral ITO structure exhibits a better broadband CD response than that of the structure composed of traditional metal Ag. Such a chiral structure provides a new method for the design of CD devices in the mid-infrared band.

Super-resolution scanning imaging based on metal-dielectric composite metamaterials.

We propose super-resolution scanning imaging by using a metamaterial composed of a silver-silicon dioxide composite covered by a layer of chromium containing one slit and a silicon dioxide substrate. By simulating a distribution of energy flow in the metamaterial for an H-polarized wave, we find that the output beam exhibits focusing accompanied with good directional radiation, which is able to be designed as a super-resolution scanning probe. We also demonstrate numerically super-resolution imaging by scanning our designed metamaterial over a sub-wavelength object.

Sleep Quality Evaluation Based on Single-Lead Wearable Cardiac Cycle Acquisition Device.

In clinical conditions, polysomnography (PSG) is regarded as the "golden standard" for detecting sleep disease and offering a reference of objective sleep quality. For healthy adults, scores from sleep questionnaires are more reliable than other methods in obtaining knowledge of subjective sleep quality. In practice, the need to simplify PSG to obtain subjective sleep quality by recording a few channels of physiological signals such as single-lead electrocardiogram (ECG) or photoplethysmography (PPG) signal is still very urgent. This study provided a two-step method to differentiate sleep quality into "good sleep" and "poor sleep" based on the single-lead wearable cardiac cycle data, with the comparison of the subjective sleep questionnaire score. First, heart rate variability (HRV) features and ECG-derived respiration features were extracted to construct a sleep staging model (wakefulness (W), rapid eye movement (REM), light sleep (N1&N2) and deep sleep (N3)) using the multi-classifier fusion method. Then, features extracted from the sleep staging results were used to construct a sleep quality evaluation model, i.e., classifying the sleep quality as good and poor. The accuracy of the sleep staging model, tested on the international public database, was 0.661 and 0.659 in Cardiology Challenge 2018 training database and Sleep Heart Health Study Visit 1 database, respectively. The accuracy of the sleep quality evaluation model was 0.786 for our recording subjects, with an average F1-score of 0.771. The proposed sleep staging model and sleep quality evaluation model only requires one channel of wearable cardiac cycle signal. It is very easy to transplant to portable devices, which facilitates daily sleep health monitoring.

A pilot study of deep learning-based CT volumetry for traumatic hemothorax.

PURPOSE: We employ nnU-Net, a state-of-the-art self-configuring deep learning-based semantic segmentation method for quantitative visualization of hemothorax (HTX) in trauma patients, and assess performance using a combination of overlap and volume-based metrics. The accuracy of hemothorax volumes for predicting a composite of hemorrhage-related outcomes - massive transfusion (MT) and in-hospital mortality (IHM) not related to traumatic brain injury - is assessed and compared to subjective expert consensus grading by an experienced chest and emergency radiologist. MATERIALS AND METHODS: The study included manually labeled admission chest CTs from 77 consecutive adult patients with non-negligible (≥ 50 mL) traumatic HTX between 2016 and 2018 from one trauma center. DL results of ensembled nnU-Net were determined from fivefold cross-validation and compared to individual 2D, 3D, and cascaded 3D nnU-Net results using the Dice similarity coefficient (DSC) and volume similarity index. Pearson's r, intraclass correlation coefficient (ICC), and mean bias were also determined for the best performing model. Manual and automated hemothorax volumes and subjective hemothorax volume grades were analyzed as predictors of MT and IHM using AUC comparison. Volume cut-offs yielding sensitivity or specificity ≥ 90% were determined from ROC analysis. RESULTS: Ensembled nnU-Net achieved a mean DSC of 0.75 (SD: ± 0.12), and mean volume similarity of 0.91 (SD: ± 0.10), Pearson r of 0.93, and ICC of 0.92. Mean overmeasurement bias was only 1.7 mL despite a range of manual HTX volumes from 35 to 1503 mL (median: 178 mL). AUC of automated volumes for the composite outcome was 0.74 (95%CI: 0.58-0.91), compared to 0.76 (95%CI: 0.58-0.93) for manual volumes, and 0.76 (95%CI: 0.62-0.90) for consensus expert grading (p = 0.93). Automated volume cut-offs of 77 mL and 334 mL predicted the outcome with 93% sensitivity and 90% specificity respectively. CONCLUSION: Automated HTX volumetry had high method validity, yielded interpretable visual results, and had similar performance for the hemorrhage-related outcomes assessed compared to manual volumes and expert consensus grading. The results suggest promising avenues for automated HTX volumetry in research and clinical care.

Entropy Analysis of Heart Rate Variability in Different Sleep Stages.

How the complexity or irregularity of heart rate variability (HRV) changes across different sleep stages and the importance of these features in sleep staging are not fully understood. This study aimed to investigate the complexity or irregularity of the RR interval time series in different sleep stages and explore their values in sleep staging. We performed approximate entropy (ApEn), sample entropy (SampEn), fuzzy entropy (FuzzyEn), distribution entropy (DistEn), conditional entropy (CE), and permutation entropy (PermEn) analyses on RR interval time series extracted from epochs that were constructed based on two methods: (1) 270-s epoch length and (2) 300-s epoch length. To test whether adding the entropy measures can improve the accuracy of sleep staging using linear HRV indices, XGBoost was used to examine the abilities to differentiate among: (i) 5 classes [Wake (W), non-rapid-eye-movement (NREM), which can be divide into 3 sub-stages: stage N1, stage N2, and stage N3, and rapid-eye-movement (REM)]; (ii) 4 classes [W, light sleep (combined N1 and N2), deep sleep (N3), and REM]; and (iii) 3 classes: (W, NREM, and REM). SampEn, FuzzyEn, and CE significantly increased from W to N3 and decreased in REM. DistEn increased from W to N1, decreased in N2, and further decreased in N3; it increased in REM. The average accuracy of the three tasks using linear and entropy features were 42.1%, 59.1%, and 60.8%, respectively, based on 270-s epoch length; all were significantly lower than the performance based on 300-s epoch length (i.e., 54.3%, 63.1%, and 67.5%, respectively). Adding entropy measures to the XGBoost model of linear parameters did not significantly improve the classification performance. However, entropy measures, especially PermEn, DistEn, and FuzzyEn, demonstrated greater importance than most of the linear parameters in the XGBoost model.300-s270-s.