Building a learnable universal coordinate system for single-cell atlas with a joint-VAE model.

A universal coordinate system that can ensemble the huge number of cells and capture their heterogeneities is of vital importance for constructing large-scale cell atlases as references for molecular and cellular studies. Studies have shown that cells exhibit multifaceted heterogeneities in their transcriptomic features at multiple resolutions. This nature of complexity makes it hard to design a fixed coordinate system through a combination of known features. It is desirable to build a learnable universal coordinate model that can capture major heterogeneities and serve as a controlled generative model for data augmentation. We developed UniCoord, a specially-tuned joint-VAE model to represent single-cell transcriptomic data in a lower-dimensional latent space with high interpretability. Each latent dimension can represent either discrete or continuous feature, and either supervised by prior knowledge or unsupervised. The latent dimensions can be easily reconfigured to generate pseudo transcriptomic profiles with desired properties. UniCoord can also be used as a pre-trained model to analyze new data with unseen cell types and thus can serve as a feasible framework for cell annotation and comparison. UniCoord provides a prototype for a learnable universal coordinate framework to enable better analysis and generation of cells with highly orchestrated functions and heterogeneities.

Core-shell structured alginate-based hydrogel beads modified by starch and protocatechuic acid: Preparation, characterization, phenolic slow release and stable antioxidant potential.

A novel core-shell structured alginate-based hydrogel bead modified by co-gelatinizing with starch and protocatechuic acid (PA), was designed to modulate physical properties of beads, release behavior and antioxidant stability of encapsulated bioactives. Core was fabricated by ionotropic gelation, and its formulation (ratio of sodium alginate/starch) was determined by particle size/starch distribution, texture and bioactive encapsulation capacity of core. Then, coating core with shell-forming solution co-gelatinized with different doses of PA, and subsequently cross-linked with Ca2+ to obtain core-shell structured beads. Surface microstructure, mechanical characteristics, and swelling ratio of beads were affected by concentrations of PA. Besides, core-shell structure containing PA could enhance delivery and sustained release of encapsulated phenolic bioactives during in vitro digestion, and improve their antioxidant potential stability. Furthermore, interaction between PA and polysaccharide components was elucidated by FTIR and TGA. The present information was beneficial for the advancement of functional food materials and bioactive delivery systems.

Potential of polyphenols from Ligustrum robustum (Rxob.) Blume on enhancing the quality of starchy food during frying.

The increasing concerns about health have led to a growing demand for high-quality fried foods. The potential uses of Ligustrum robustum (Rxob.) Blume, a traditional tea in China, as natural additives to enhance the quality of starchy food during frying was studied. Results indicated that L. robustum polyphenols extract (LREs) could improve the quality of fried starchy food, according to the tests of color, moisture content, oil content, texture property, and volatile flavor. The in vitro digestion results demonstrated that LRE reduced the final glucose content from 11.35 ± 0.17 to 10.80 ± 0.70 mmol/L and increased the phenolic content of fried starch foods from 1.23 ± 0.04 to 3.76 ± 0.14 mg/g. The appearance and polarizing microscopy results showed that LRE promoted large starch bulges on the surface of fried starchy foods. Meanwhile, X-ray diffraction results showed that LRE increased the intensity of characteristic diffraction peak of fried starch with a range of 21.8%-28%, and Fourier transform infrared results showed that LRE reduced the damage to short-range order structure of starch caused by the frying process. In addition, LRE increased the aggregation of starch granules according to the SEM observation and decreased the enthalpy of starch gelatinization based on the differential scanning calorimetry results. The present results suggest that LREs have the potential to be utilized as a natural additive for regulating the quality of fried starchy food in food industries. PRACTICAL APPLICATION: The enhancement of L. robustum polyphenols on the quality of starchy food during frying was found, and its mechanisms were also explored. This work indicated that L. robustum might be used as a novel economic natural additive for producing high-quality fried foods.

Elucidating the influence and mechanism of different phenols on the properties, food quality and function of maize starch.

This study discusses interaction differences between three phenols (protocatechuic acid, naringin and tannic acid) and starch helix, investigates influences of phenols at different doses on properties of maize starch, and further determines their effects on quality and function of maize-starchy foods. Simulated results indicate variations of phenolic structure (phenolic hydroxyl group amount, glycoside structure and steric hindrance) and dose induce phenols form different complexes with starch helix. Formation of different starch-phenols complexes alters gelatinization (1.65-5.63 J/g), pasting form, water binding capacity (8.83-12.69 g/g) and particle size distribution of starch. Meanwhile, differences in starch-phenols complexes are reflected in fingerprint area (R1045/1022: 0.920 to 1.047), crystallinity (8.3% to 17.0%), rheology and gel structure of starch. Additionally, phenols change texture and color of cold maize cake, giving them different antioxidant capacity and lower digestibility. Findings are beneficial for understanding interaction between starch and different phenols and their potential application.

Elucidating effects of Epiphyllum oxypetalum (DC.) Haw polysaccharide on the physicochemical and digestive properties of tapioca starch.

Effects of Epiphyllum oxypetalum (DC.) Haw polysaccharide (EP) on physicochemical/digestive properties of tapioca starch (TS) were investigated, and its effects on final quality of TS-based foods were further determined. Results showed EP significantly decreased gelatinization enthalpy (3.92 to 2.11 J/g) and increased breakdown (302 to 382 cp), thereby inducing the gelatinization of TS. Meanwhile, EP decreased setback viscosity (324 to 258 cp), suggesting the retrogradation of TS paste was inhibited. Rheological determination results suggested EP had an impact on the viscoelasticity of TS paste. Moreover, particle size distribution showed EP increased size of TS by cross-linking. Additionally, the suitable addition of EP ameliorated the microstructure and decreased the crystal diffraction peak area of TS gel. Infrared spectroscopy results revealed EP modified the above properties of TS by hydrogen bonds and non-covalent forces. Furthermore, EP inhibited the in vitro digestion of TS paste. Using taro balls as TS-based food model, appropriate addition of EP (0.10 %) improved texture properties, frozen storage stability and color of samples. The present results can not only facilitate the understanding of the modification mechanism of EP on the properties of TS, but also induce the burgeoning of starchy products and the possible application of EP in foods.

STEM enables mapping of single-cell and spatial transcriptomics data with transfer learning.

Profiling spatial variations of cellular composition and transcriptomic characteristics is important for understanding the physiology and pathology of tissues. Spatial transcriptomics (ST) data depict spatial gene expression but the currently dominating high-throughput technology is yet not at single-cell resolution. Single-cell RNA-sequencing (SC) data provide high-throughput transcriptomic information at the single-cell level but lack spatial information. Integrating these two types of data would be ideal for revealing transcriptomic landscapes at single-cell resolution. We develop the method STEM (SpaTially aware EMbedding) for this purpose. It uses deep transfer learning to encode both ST and SC data into a unified spatially aware embedding space, and then uses the embeddings to infer SC-ST mapping and predict pseudo-spatial adjacency between cells in SC data. Semi-simulation and real data experiments verify that the embeddings preserved spatial information and eliminated technical biases between SC and ST data. We apply STEM to human squamous cell carcinoma and hepatic lobule datasets to uncover the localization of rare cell types and reveal cell-type-specific gene expression variation along a spatial axis. STEM is powerful for mapping SC and ST data to build single-cell level spatial transcriptomic landscapes, and can provide mechanistic insights into the spatial heterogeneity and microenvironments of tissues.

Dynamic atlas of immune cells reveals multiple functional features of macrophages associated with progression of pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a high mortality rate and unclarified aetiology. Immune response is elaborately regulated during the progression of IPF, but immune cells subsets are complicated which has not been detailed described during IPF progression. Therefore, in the current study, we sought to investigate the role of immune regulation by elaborately characterize the heterogeneous of immune cells during the progression of IPF. To this end, we performed single-cell profiling of lung immune cells isolated from four stages of bleomycin-induced pulmonary fibrosis-a classical mouse model that mimics human IPF. The results revealed distinct components of immune cells in different phases of pulmonary fibrosis and close communication between macrophages and other immune cells along with pulmonary fibrosis progression. Enriched signals of SPP1, CCL5 and CXCL2 were found between macrophages and other immune cells. The more detailed definition of the subpopulations of macrophages defined alveolar macrophages (AMs) and monocyte-derived macrophages (mo-Macs)-the two major types of primary lung macrophages-exhibited the highest heterogeneity and dynamic changes in expression of profibrotic genes during disease progression. Our analysis suggested that Gpnmb and Trem2 were both upregulated in macrophages and may play important roles in pulmonary fibrosis progression. Additionally, the metabolic status of AMs and mo-Macs varied with disease progression. In line with the published data on human IPF, macrophages in the mouse model shared some features regarding gene expression and metabolic status with that of macrophages in IPF patients. Our study provides new insights into the pathological features of profibrotic macrophages in the lung that will facilitate the identification of new targets for disease intervention and treatment of IPF.

Green Cleaning of 3D-Printed Polymeric Products by Micro-/Nano-Bubbles.

3D printing technology has been used to directly produce various actual products, ranging from engines and medicines to toys, especially due to its advantage in producing items of complicated, porous structures, which are inherently difficult to clean. Here, we apply micro-/nano-bubble technology to the removal of oil contaminants from 3D-printed polymeric products. Micro-/nano-bubbles show promise in the enhancement of cleaning performance with or without ultrasound, which is attributed to their large specific surface area enhancing the adhesion sites of contaminants, and their high Zeta potential which attracts contaminant particles. Additionally, bubbles produce tiny jets and shock waves at their rupture, driven by coupled ultrasound, which can remove sticky contaminants from 3D-printed products. As an effective, efficient, and environmentally friendly cleaning method, micro-/nano-bubbles can be used in a range of applications.

Potato Starch-Based Film Incorporated with Tea Polyphenols and Its Application in Fruit Packaging.

Effects of tea polyphenols (TP) on the physical properties, barrier properties and functionality of potato starch-based film were determined, while the interaction mechanism between TP and starch in film and the application of this film in fruit packaging were further evaluated. TP exhibited different effects on the physical properties of potato starch-based film, including thickness (0.083 to 0.087 mm), moisture content (9.27% to 9.68%), color (ΔE value: 5.41 to 10.55), light transmittance (51% to 62%), tensile properties and thermal properties, and improved its barrier properties, including water vapor permeability (9.68 to 11.84 × 10-11 g m-1 s-1 Pa-1),oxygen permeability (1.25 to 2.78 × 10-16 g m-1 s-1 Pa-1) and antioxidant activity. According to the determination of wide-angle X-ray diffraction, Fourier transform infrared and scanning electron microscope, TP could interact with starch chains via hydrogen bonds to form non-crystal complexes, thus affecting the cross-linking among starch chains and further changing the microstructure of film. Furthermore, film incorporated with TP could improve the storage quality (including weight and texture) of blueberries, and inhibit the enzymatic browning of fresh-cut bananas during storage. All present results suggested that tea polyphenols had potential to enhance the properties and function of potato starch-based film, and the film exhibited the application prospect in fruit packaging and preservation.

Insight into property, function, and digestion of potato starch modified by phenolic compounds with varying structures.

Influences of structural characteristics of phenolic compounds on the properties of potato starch were investigated, and their effects on the quality, function, and digestion of potato starch noodles were further determined. All testing phenolic compounds (including protocatechuic acid [PA], naringin [NA], and tannic acid [TA]) exhibited the significant capability to modify the thermal properties, rheological properties, and enzymatic hydrolysis of potato starch. The high amount of hydroxyl groups, the presence of glycoside structure, appropriate molecular size, and steric hindrance were beneficial to enhance their effects on potato starch. In addition, by changing the microstructure of starch hydrocolloids, PA, NA, and TA could affect the color, texture properties, and cooking properties of potato starch noodles. Meanwhile, PA and TA could endow potato starch noodles with remarkable antioxidant activity. Furthermore, the in vitro digestion of potato starch noodles was obviously inhibited by phenolic compounds, especially for TA. All present results suggested that structural characteristics of phenolic compounds affected their interaction affinity and combination degree with potato starch molecules, so as to modify the properties of starch and affect the quality, function, and digestion of starchy foods, which showed the valuable applications in food and chemical industries. PRACTICAL APPLICATION: The property, function, and digestion characteristics of potato starch show the significant effects on the quality of potato starch products in food industry. In present study, the thermal properties, rheological properties, and enzymatic hydrolysis of potato starch were modified by different phenolic compounds (including protocatechuic acid, naringin, and tannic acid) in varying degrees, whereas the quality, antioxidant activity, and digestion characteristic of potato starch noodles were modified by phenolic compounds with different structures. All results showed the potential application and interaction regularities of phenolic compounds as natural additives for potato starch processing in food industry.

The autumn activity patterns and time budgets of Forest musk deer (Moschus berezovskii) in captivity.

Activity patterns and time budgets play a crucial role in the successful farming and management of animals. In this study, the behavior patterns of 53 forest musk deer (Moschus berezovskii) were analyzed from October 2nd to 16th, 2021, throughout the day and night. The results showed a distinct dawn-dusk activity rhythm in the captive forest musk deer with a peak activity observed at dawn (07:00 - 10:00) and dusk (16:00 - 19:00). Additionally, there were smaller activity peaks lasting less than an hour during the nighttime (00:00 - 04:00). Comparing behavior ratios between peak and off-peak periods, it was evident that all behaviors, except rumination (RU), showed significant differences. Furthermore, no significant differences were found in the behavior ratios of the forest musk deer between the daytime and night-time. During the daytime, the percentages of time spent performing locomotion (32.87 ± 3.38%), feeding (14.43 ± 1.81%), and RU (5.62 ± 1.46%) were slightly higher compared to the night-time. Based on these findings, it is important to match the management strategies for musk deer farming with the animals' activity patterns and behavioral rhythms. Doing so can enhance farming outputs and contribute to the welfare of captive forest musk deer.

Cellular features of localized microenvironments in human meniscal degeneration: a single-cell transcriptomic study.

Background: Musculoskeletal tissue degeneration impairs the life quality and function of many people. Meniscus degeneration is a major origin of knee osteoarthritis and a common threat to athletic ability, but its cellular mechanism remains elusive. Methods: We built a cell atlas of 12 healthy or degenerated human meniscus samples from the inner and outer meniscal zones of 8 patients using scRNA-seq to investigate meniscal microenvironment homeostasis and its changes in the degeneration process and verified findings with immunofluorescent imaging. Results: We identified and localized cell types in inner and outer meniscus and found new chondrocyte subtypes associated with degeneration. The observations suggested understandings on how cellular compositions, functions, and interactions participated in degeneration, and on the possible loop-like interactions among extracellular matrix disassembly, angiogenesis, and inflammation in driving the degeneration. Conclusions: The study provided a rich resource reflecting variations in the meniscal microenvironment during degeneration and suggested new cell subtypes as potential therapeutic targets. The hypothesized mechanism could also be a general model for other joint degenerations. Funding: The National Natural Science Foundation of China (81972123, 82172508, 62050178, 61721003), the National Key Research and Development Program of China (2021YFF1200901), Fundamental Research Funds for the Central Universities (2015SCU04A40); The Innovative Spark Project of Sichuan University (2018SCUH0034); Sichuan Science and Technology Program (2020YFH0075); Chengdu Science and Technology Bureau Project (2019-YF05-00090-SN); 1.3.5 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYJC21030, ZY2017301); 1.3.5 Project for Disciplines of Excellence - Clinical Research Incubation Project, West China Hospital, Sichuan University (2019HXFH039).

Effects of Ligustrum robustum (Rxob.) Blume extract on the quality of peanut and palm oils during storage and frying process.

The potential uses of Ligustrum robustum (Rxob.) Blume extract as a natural antioxidant to protect the quality of different oils during storage and frying process were studied. The results showed that L. robustum extract has been shown to retard the decline in the quality of both oils based on the tests of acid value, peroxide value, p-anisidine value, color, volatile flavor, and fatty acid compositions, and the protective effect of L. robustum extract on the quality of peanut oil was better than that of palm oil. By the component analysis, L. robustum extract was found to have a total phenols content of 140.75 ± 1.52 mg/g, and ligurobustoside C was identified as the main phenolic compound. The thermogravimetric and differential scanning calorimetry results showed that L. robustum extract enhanced the oxidative stability of peanut and palm oils. In addition, Fourier transform infrared results indicated that L. robustum extract had protective effects on the C=C bond and ester bond of oil molecule. Moreover, by using electron spin resonance technique, L. robustum extract showed the ability to inhibit and scavenge alkyl-free radicals in both oils. The present results suggested that L. robustum extract may protect the quality of oils during the storage and frying process by inhibiting the oxidation of unsaturated fatty acids and might be a potential natural antioxidant in the food industry. PRACTICAL APPLICATIONS: The excellent antioxidant ability of Ligustrum robustum (Rxob.) Blume extract on the oxidation of different oils and its low price indicated that it could be used as a new low-cost natural antioxidant in oil processing.

Protocol for profiling cell-centric assembled single-cell human transcriptome data in hECA.

Human Ensemble Cell Atlas (hECA) provides a unified informatics framework and the cell-centric-assembled single-cell transcriptome data of 1,093,299 labeled human cells from 116 published datasets. In this protocol, we provide three applications of hECA: "quantitative portraiture" exploration with websites, customizable reference creation for automatic cell type annotation, and "in data" cell sorting with logical conditions. We provide detail steps of connecting to the database, searching cell with conditions, downloading data, and annotating new datasets with customized reference. For complete details on the use and execution of this protocol, please refer to Chen et al. (2022).

hECA: The cell-centric assembly of a cell atlas.

The accumulation of massive single-cell omics data provides growing resources for building biomolecular atlases of all cells of human organs or the whole body. The true assembly of a cell atlas should be cell-centric rather than file-centric. We developed a unified informatics framework for seamless cell-centric data assembly and built the human Ensemble Cell Atlas (hECA) from scattered data. hECA v1.0 assembled 1,093,299 labeled human cells from 116 published datasets, covering 38 organs and 11 systems. We invented three new methods of atlas applications based on the cell-centric assembly: "in data" cell sorting for targeted data retrieval with customizable logic expressions, "quantitative portraiture" for multi-view representations of biological entities, and customizable reference creation for generating references for automatic annotations. Case studies on agile construction of user-defined sub-atlases and "in data" investigation of CAR-T off-targets in multiple organs showed the great potential enabled by the cell-centric ensemble atlas.

Toward a unified information framework for cell atlas assembly.

This perspective discusses the need and directions for the development of a unified information framework to enable the assembly of cell atlases and a revolution in medical research on the virtual body of assembled cell systems.

Potential of phenolic compounds in Ligustrum robustum (Rxob.) Blume as antioxidant and lipase inhibitors: Multi-spectroscopic methods and molecular docking.

Ligustrum robustum (Rxob.) Blume is traditionally served as a functional tea in China. In this work, the antioxidant activities of L. robustum (Rxob.) Blume extract (LRE) were evaluated and its inhibitory effect and mechanism on pancreatic lipase were further investigated. With the high contents of phenols (139.70 ± 1.41 mg gallic acid equivalent/g extract) and flavonoids (326.46 ± 7.36 mg rutin equivalent/g extract), LRE showed significant antioxidant activities (p < 0.05) for scavenging free radicals and hydrogen peroxide, inhibiting lipid peroxidation and providing strong reducing power. Meanwhile, LRE displayed remarkable inhibitory activity on pancreatic lipase with a low half-effective inhibitory concentration (IC50 ) of 2.469 ± 0.005 mg/ml which was further determined as non-competitive inhibition. The spectroscopic results showed that LRE inhibited the activity of pancreatic lipase by modifying the tertiary and secondary structures of lipase. Moreover, four phenolic compounds (acteoside, lipedoside A, oleuropein and ligurobustoside C) were identified from LRE by the high performance liquid chromatography-quadrupole- time of flight-mass spectrometry. In addition, according to molecular docking analysis, the four phenols could interact with pancreatic lipase by hydrogen bonds, so as to change the spatial structure of pancreatic lipase and inhibit its catalytic activity. The present results suggest that LRE not only exhibits strong antioxidant capacity but possesses effectively inhibitory activity on pancreatic lipase, which might have the potential to be developed as functional food and nutraceuticals for the prevention of metabolic diseases. PRACTICAL APPLICATION: Ligustrum robustum (Rxob.) Blume extract has been confirmed to possess antioxidant activity and lipase inhibitory activity, which indicates that the L. robustum extract has the potential to prevent oxidative stress and regulate fat metabolism. This work suggests that L. robustum extract can be served as a novel resource to prepare nutraceuticals and functional food in food industries.

Wheat Starch Modified with Ligustrum robustum (Rxob.) Blume Extract and Its Action Mechanism.

We investigated the modification of wheat starch with Ligustrum robustum (Rxob.) Blume extract (LRE) and determined the action mechanism. Based on differential scanning calorimetry, LRE decreased the gelatinization enthalpy of wheat starch from 19.14 to 7.15 J/g and changed gelatinization temperatures (including the variation in gelatinization onset temperature, peak temperature and conclusion temperature in different degrees). Moreover, LRE affected the pasting viscosity curve of wheat starch, and changed its rheological parameters (including the decrease in storage modulus and loss modulus, as well as the increase in loss tangent). Based on the analysis of scanning electron microscopy and wide-angle X-ray diffraction, LRE increased the hole size and the roughness of the gel microstructure, and decreased the crystallinity of wheat starch. Meanwhile, the evaluation results of the texture analyzer and the colorimeter showed that LRE could change the quality properties (including decrease hardness, fracturability and L* values, as well as increase a* and b* values) of wheat starch biscuits after hot air baking (170 °C). Furthermore, with molecular dynamics simulation analysis, phenolic compounds of LRE combined with starch molecules via H-bonds and affected the formation of molecular bonds (including intra- and intermolecular hydrogen bonds), so as to change the spatial conformation and properties of wheat starch during gelatinization and retrogradation. The present results suggest that LRE can modify the physicochemical properties of wheat starch and further improve its processing properties, indicating its potential in the design and development of starch foods (such as steamed buns, bread, biscuits, etc.).

An Experiment on Ab Initio Discovery of Biological Knowledge from scRNA-Seq Data Using Machine Learning.

Expectations of machine learning (ML) are high for discovering new patterns in high-throughput biological data, but most such practices are accustomed to relying on existing knowledge conditions to design experiments. Investigations of the power and limitation of ML in revealing complex patterns from data without the guide of existing knowledge have been lacking. In this study, we conducted systematic experiments on such ab initio knowledge discovery with ML methods on single-cell RNA-sequencing data of early embryonic development. Results showed that a strategy combining unsupervised and supervised ML can reveal major cell lineages with minimum involvement of prior knowledge or manual intervention, and the ab initio mining enabled a new discovery of human early embryonic cell differentiation. The study illustrated the feasibility, significance, and limitation of ab initio ML knowledge discovery on complex biological problems.