Cross-species single-cell analysis uncovers the immunopathological mechanisms associated with IgA nephropathy progression.

IgA nephropathy (IgAN) represents the main cause of renal failure, while the precise pathogenetic mechanisms have not been fully determined. Herein, we conducted a cross-species single-cell survey on human IgAN and mouse and rat IgAN models to explore the pathogenic programs. Cross-species single-cell RNA sequencing (scRNA-Seq) revealed that the IgAN mesangial cells (MCs) expressed high levels of inflammatory signatures CXCL12, CCL2, CSF1, and IL-34 and specifically interacted with IgAN macrophages via the CXCL12/CXCR4, CSF1/IL-34/CSF1 receptor, and integrin subunit alpha X/integrin subunit alpha M/complement C3 (C3) axes. IgAN macrophages expressed high levels of CXCR4, PDGFB, triggering receptor expressed on myeloid cells 2, TNF, and C3, and the trajectory analysis suggested that these cells derived from the differentiation of infiltrating blood monocytes. Additionally, protein profiling of 21 progression and 28 nonprogression IgAN samples revealed that proteins CXCL12, C3, mannose receptor C-type 1, and CD163 were negatively correlated with estimated glomerular filtration rate (eGFR) value and poor prognosis (30% eGFR as composite end point). Last, a functional experiment revealed that specific blockade of the Cxcl12/Cxcr4 pathway substantially attenuated the glomerulus and tubule inflammatory injury, fibrosis, and renal function decline in the mouse IgAN model. This study provides insights into IgAN progression and may aid in the refinement of IgAN diagnosis and the optimization of treatment strategies.

Extraction, characterization and intestinal anti-inflammatory and anti-oxidative activities of polysaccharide from stems and leaves of Chuanminshen violaceum M. L. Sheh & R. H. Shan.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. MATERIALS AND METHODS: The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-Ⅰ in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. RESULTS: The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-Ⅰ (35.34 kDa), and the structural characterization indicated that CVP-AP-Ⅰ was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-Ⅰ attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. CONCLUSION: The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases.

Anisotropic optical property of ferroelectric Bi2O2X(X = S,Se,Te) monolayer and strain engineering.

Based on the first-principles calculations, ferroelectricBi2O2X(X=S,Se,Te)monolayers with unequivalent in-plane lattice constants are confirmed to be the ground state, which is consistent with the experiment result (Ghoshet al2019Nano Lett.195703-09), and the anisotropic optical property is firstly investigated. We find that the polarizations ofBi2O2Xmonolayers points along the direction ofa-axis, andBi2O2Temonolayer process the largest polarization. Furthermore, both the biaxial and uniaxial strains are favor for the enhancement of polarization ofBi2O2Xmonolayers. It should be mentioned that the type of band gap will convert from indirect to direct forBi2O2Temonolayer when thea-axial tensile strain is larger than 2%. At last, the optical absorption coefficient forBi2O2Xmonolayers are calculated, and we obtain thatBi2O2Temonolayer has the strongest optical absorption within the range of visible light, the anisotropy and possible strain engineering to improve the optical absorption are discussed in detail. Our findings are significant in fields of optoelectronics and photovoltaics.

Ultrasonic-assisted extraction of polysaccharide from Paeoniae Radix alba: Extraction optimization, structural characterization and antioxidant mechanism in vitro.

Paeoniae Radix alba is used in Traditional Chinese Medicine for the treatment of gastrointestinal disorders, immunomodulatory, cancer, and other diseases. In the current study, the yield of Paeoniae Radix alba polysaccharide (PRP) was significantly increased with optimal ultrasound-assisted extraction compared to hot water extraction. Further, an acidic polysaccharide (PRP-AP) was isolated from PRP after chromatographic separation and was characterized as a typical pectic polysaccharide with side chains of arabinogalactans types I and II. Moreover, it showed antioxidant effects on LPS-induced damage on IPEC-J2 cells determined by qRT-PCR and ELISA, including decreasing the pro-inflammatory factors' expressions and increasing the antioxidant enzymes activities, which was shown to be related to the Nrf2/Keap1 pathway modulated by PRP-AP. The metabolites change (such as itaconate, cholesterol sulfate, etc.) detected by untargeted metabolomic analysis in cells was also shown to be modulated by PRP-AP, and these metabolites were further utilized and protected cells damaged by LPS. These results revealed the cellular active mechanism of the macromolecular PRP-AP on protecting cells, and supported the hypothesis that PRP-AP has strong benefits as an alternative dietary supplement for the prevention of intestinal oxidative stress by modulating cellular metabolism.

Coexisting Magnetism, Ferroelectric, and Ferrovalley Multiferroic in Stacking-Dependent Two-Dimensional Materials.

Two-dimensional (2D) multiferroic materials have widespread application prospects in facilitating the integration and miniaturization of nanodevices. However, the magnetic, ferroelectric, and ferrovalley properties in one 2D material are rarely coupled. Here, we propose a mechanism for manipulating magnetism, ferroelectric, and valley polarization by interlayer sliding in a 2D bilayer material. Monolayer GdI2 is a ferromagnetic semiconductor with a valley polarization of up to 155.5 meV. More interestingly, the magnetism and valley polarization of bilayer GdI2 can be strongly coupled by sliding ferroelectricity, making these tunable and reversible. In addition, we uncover the microscopic mechanism of the magnetic phase transition by a spin Hamiltonian and electron hopping between layers. Our findings offer a new direction for investigating 2D multiferroic devices with implications for next-generation electronic, valleytronic, and spintronic devices.

Chromones from the endophytic fungus Bipolaris eleusines.

Eight previously undescribed chromones eleusineketones A-H (1-8), as well as eight known compounds (9-16), were isolated from the endophytic fungus Bipolaris eleusines. These planar structures were created using an in-depth analysis of their spectral data, which included 1D, 2D, and HRESIMS data. Furthermore, the absolute configurations of compounds 1, 2, and 6 were determined by spectroscopic analysis and quantum chemical computational approaches, and compound 5 was determined by single-crystal X-ray diffraction analysis. The cytotoxic activity assay revealed that compounds 1 and 5 both inhibited MDA-MB-231 cells with IC50 values of 14.48 µM and 17.99 µM, respectively.

Optimization of synchrotron radiation parameters using swarm intelligence and evolutionary algorithms.

Alignment of each optical element at a synchrotron beamline takes days, even weeks, for each experiment costing valuable beam time. Evolutionary algorithms (EAs), efficient heuristic search methods based on Darwinian evolution, can be utilized for multi-objective optimization problems in different application areas. In this study, the flux and spot size of a synchrotron beam are optimized for two different experimental setups including optical elements such as lenses and mirrors. Calculations were carried out with the X-ray Tracer beamline simulator using swarm intelligence (SI) algorithms and for comparison the same setups were optimized with EAs. The EAs and SI algorithms used in this study for two different experimental setups are the Genetic Algorithm (GA), Non-dominated Sorting Genetic Algorithm II (NSGA-II), Particle Swarm Optimization (PSO) and Artificial Bee Colony (ABC). While one of the algorithms optimizes the lens position, the other focuses on optimizing the focal distances of Kirkpatrick-Baez mirrors. First, mono-objective evolutionary algorithms were used and the spot size or flux values checked separately. After comparison of mono-objective algorithms, the multi-objective evolutionary algorithm NSGA-II was run for both objectives - minimum spot size and maximum flux. Every algorithm configuration was run several times for Monte Carlo simulations since these processes generate random solutions and the simulator also produces solutions that are stochastic. The results show that the PSO algorithm gives the best values over all setups.

Instantaneous estimation of momentary affective responses using neurophysiological signals and a spatiotemporal emotional intensity regression network.

Previous studies in affective computing often use a fixed emotional label to train an emotion classifier with electroencephalography (EEG) from individuals experiencing an affective stimulus. However, EEGs encode emotional dynamics that include varying intensities within a given emotional category. To investigate these variations in emotional intensity, we propose a framework that obtains momentary affective labels for fine-grained segments of EEGs with human feedback. We then model these labeled segments using a novel spatiotemporal emotional intensity regression network (STEIR-Net). It integrates temporal EEG patterns from nine predefined cortical regions to provide a continuous estimation of emotional intensity. We demonstrate that the STEIR-Net outperforms classical regression models by reducing the root mean square error (RMSE) by an average of 4∼9 % and 2∼4 % for the SEED and SEED-IV databases, respectively. We find that the frontal and temporal cortical regions contribute significantly to the affective intensity's variation. Higher absolute values of the Spearman correlation coefficient between the model estimation and momentary affective labels under happiness (0.2114) and fear (0.2072) compared to neutral (0.1694) and sad (0.1895) emotions were observed. Besides, increasing the input length of the EEG segments from 4 to 20 s further reduces the RMSE from 1.3548 to 1.3188.

High-harmonic spectroscopy of low-energy electron-scattering dynamics in liquids.

High-harmonic spectroscopy is an all-optical nonlinear technique with inherent attosecond temporal resolution. It has been applied to a variety of systems in the gas phase and solid state. Here we extend its use to liquid samples. By studying high-harmonic generation over a broad range of wavelengths and intensities, we show that the cut-off energy is independent of the wavelength beyond a threshold intensity and that it is a characteristic property of the studied liquid. We explain these observations with a semi-classical model based on electron trajectories that are limited by the electron scattering. This is further confirmed by measurements performed with elliptically polarized light and with ab-initio time-dependent density functional theory calculations. Our results propose high-harmonic spectroscopy as an all-optical approach for determining the effective mean free paths of slow electrons in liquids. This regime is extremely difficult to access with other methodologies, but is critical for understanding radiation damage to living tissues. Our work also indicates the possibility of resolving subfemtosecond electron dynamics in liquids offering an all-optical approach to attosecond spectroscopy of chemical processes in their native liquid environment.

A chromosome-level genome assembly for the Silkie chicken resolves complete sequences for key chicken metabolic, reproductive, and immunity genes.

A set of high-quality pan-genomes would help identify important genes that are still hidden/incomplete in bird reference genomes. In an attempt to address these issues, we have assembled a de novo chromosome-level reference genome of the Silkie (Gallus gallus domesticus), which is an important avian model for unique traits, like fibromelanosis, with unclear genetic foundation. This Silkie genome includes the complete genomic sequences of well-known, but unresolved, evolutionarily, endocrinologically, and immunologically important genes, including leptin, ovocleidin-17, and tumor-necrosis factor-α. The gap-less and manually annotated MHC (major histocompatibility complex) region possesses 38 recently identified genes, with differentially regulated genes recovered in response to pathogen challenges. We also provide whole-genome methylation and genetic variation maps, and resolve a complex genetic region that may contribute to fibromelanosis in these animals. Finally, we experimentally show leptin binding to the identified leptin receptor in chicken, confirming an active leptin ligand-receptor system. The Silkie genome assembly not only provides a rich data resource for avian genome studies, but also lays a foundation for further functional validation of resolved genes.

Selection on the promoter regions plays an important role in complex traits during duck domestication.

BACKGROUND: Identifying the key factors that underlie complex traits during domestication is a great challenge for evolutionary and biological studies. In addition to the protein-coding region differences caused by variants, a large number of variants are located in the noncoding regions containing multiple types of regulatory elements. However, the roles of accumulated variants in gene regulatory elements during duck domestication and economic trait improvement are poorly understood. RESULTS: We constructed a genomics, transcriptomics, and epigenomics map of the duck genome and assessed the evolutionary forces that have been in play across the whole genome during domestication. In total, 304 (42.94%) gene promoters have been specifically selected in Pekin duck among all selected genes. Joint multi-omics analysis reveals that 218 genes (72.01%) with selected promoters are located in open and active chromatin, and 267 genes (87.83%) with selected promoters were highly and differentially expressed in domestic trait-related tissues. One important candidate gene ELOVL3, with a strong signature of differentiation on the core promoter region, is known to regulate fatty acid elongation. Functional experiments showed that the nearly fixed variants in the top selected ELOVL3 promoter in Pekin duck decreased binding ability with HLF and increased gene expression, with the overexpression of ELOVL3 able to increase lipid deposition and unsaturated fatty acid enrichment. CONCLUSIONS: This study presents genome resequencing, RNA-Seq, Hi-C, and ATAC-Seq data of mallard and Pekin duck, showing that selection of the gene promoter region plays an important role in gene expression and phenotypic changes during domestication and highlights that the variants of the ELOVL3 promoter may have multiple effects on fat and long-chain fatty acid content in ducks.

Electron population dynamics in resonant non-linear x-ray absorption in nickel at a free-electron laser.

Free-electron lasers provide bright, ultrashort, and monochromatic x-ray pulses, enabling novel spectroscopic measurements not only with femtosecond temporal resolution: The high fluence of their x-ray pulses can also easily enter the regime of the non-linear x-ray-matter interaction. Entering this regime necessitates a rigorous analysis and reliable prediction of the relevant non-linear processes for future experiment designs. Here, we show non-linear changes in the L3-edge absorption of metallic nickel thin films, measured with fluences up to 60 J/cm2. We present a simple but predictive rate model that quantitatively describes spectral changes based on the evolution of electronic populations within the pulse duration. Despite its simplicity, the model reaches good agreement with experimental results over more than three orders of magnitude in fluence, while providing a straightforward understanding of the interplay of physical processes driving the non-linear changes. Our findings provide important insights for the design and evaluation of future high-fluence free-electron laser experiments and contribute to the understanding of non-linear electron dynamics in x-ray absorption processes in solids at the femtosecond timescale.

High-harmonic generation in liquids with few-cycle pulses: effect of laser-pulse duration on the cut-off energy.

High-harmonic generation (HHG) in liquids is opening new opportunities for attosecond light sources and attosecond time-resolved studies of dynamics in the liquid phase. In gas-phase HHG, few-cycle pulses are routinely used to create isolated attosecond pulses and to extend the cut-off energy. Here, we study the properties of HHG in liquids, including heavy water, ethanol and isopropanol, by continuously tuning the pulse duration of a mid-infrared driver from the multi- to the two-cycle regime. Similar to the gas phase, we observe the transition from discrete odd-order harmonics to continuous extreme-ultraviolet emission. However, the cut-off energy is shown to be entirely independent of the pulse duration. These observations are confirmed by ab-initio simulations of HHG in large liquid clusters. Our results support the notion that the cut-off energy is a fundamental property of the liquid, independent of the driving-pulse properties. Our work implies that few-cycle mid-infrared laser pulses are suitable drivers for generating isolated attosecond pulses from liquids and confirm the capability of high-harmonic spectroscopy to determine the mean-free paths of slow electrons in liquids.

The antifungal properties of terpenoids from the endophytic fungus Bipolaris eleusines.

A series of terpenoids (1-17), comprising six new compounds designated bipolariterpenes A-F (1-6) and eleven recognized compounds (7-17), were isolated from the wheat culture of the potato endophytic fungus Bipolaris eleusines. Their structures and stereochemistry were clarified by HRESIMS, NMR, DP4 + probability analyses, and computations for electronic circular dichroism (ECD). All compounds are made up of six meroterpenoids, four sesterterpenes and seven sesquiterpenes. Among them, four sesterterpenes (4, 5, 10, 11) were investigated for their antifungal, antibacterial and cytotoxic properties, and six meroterpenoids (1-3, 7-9) were evaluated for their antifungal properties. The compounds 7, 9, and 10 had substantial antifungal activity against Epidermophyton floccosum at a concentration of 100 µM. No antibacterial and cytotoxic activities were observed.

Tailoring angle dependent ferroelectricity in nanoribbons of group-IV monochalcogenides.

Ferroelectricity is significant in low dimensional structures due to the potential applications in multifunctional nanodevices. In this work, the tailoring angle dependent ferroelectricity is systematically investigated for the nanoribbons and nanowires of puckered group-IV monochalcogenides MX (M =Ge,Sn; X =S,Se). Based on first-principles calculations, it is found that the ferroelectricity of nanoribbon and nanowire strongly depends on the tailoring angle. Firstly, the critical width for the bare nanoribbon of group-IV monochalcogenide is obtained and discussed. As the nanowires are concerned, the ferroelectricity will disappear when the tailoring angle becomes small. At last, H-passivation on the edge and the strain engineering are employed to improve the ferroelectricity of nanoribbon, and it is obtained that H-passivation is beneficial to the enhancement of polarization for nanoribbons tailored near the armchair direction, while the polarization of nanoribbons tailored along the diagonal direction will decrease when the edges are passivated with H atoms, and the tensile strain along the length direction always favors the improvement of ferroelectricity of the considered nanoribbons. Therefore, tailoring angle has great influence on the ferroelectricity of nanoribbons and nanowires, which may be used as an effective way to tune the ferroelectricity and further the electronic structures of nanostructures in the field of nanoelectronics.

The Effect of Polymer Elastic Particles Modified with Nano-Silica on the Mechanical Properties of Oil Well Cement-Based Composite Materials.

The integrity of oil well cement sheaths is closely related to the long-term production safety of oil and gas wells. The primary material used to form a cement sheath is brittle. In order to reduce the brittleness of oil well cement and improve its flexibility and resistance to stress damage, nano-silica was used to modify polymer elastic particles, and their properties were analyzed. The influence of the modified polymer particles on the properties of oil well cement-based composite materials was studied, and the microstructure of the polymer particle cement sample was analyzed. The results showed that nano-silica effectively encapsulates polymer particles, improves their hydrophilicity, and achieves a maximum temperature resistance of 415 °C. The effect of the modified polymer particles on the compressive strength of cement sample is reduced. Polymer particles with different dosages can effectively reduce the elastic modulus of cement paste, improve the deformation and elasticity of cement paste, and enhance the toughness of cement paste. Microstructural analysis showed that the polymer particles are embedded in the hydration products, which is the main reason for the improvement in the elasticity of cement paste. At the same time, polymer particle cement slurry can ensure the integrity of the cement sample after it is impacted, which helps to improve the ability of oil well cement-based composite materials to resist stress damage underground.

Femtosecond proton transfer in urea solutions probed by X-ray spectroscopy.

Proton transfer is one of the most fundamental events in aqueous-phase chemistry and an emblematic case of coupled ultrafast electronic and structural dynamics1,2. Disentangling electronic and nuclear dynamics on the femtosecond timescales remains a formidable challenge, especially in the liquid phase, the natural environment of biochemical processes. Here we exploit the unique features of table-top water-window X-ray absorption spectroscopy3-6 to reveal femtosecond proton-transfer dynamics in ionized urea dimers in aqueous solution. Harnessing the element specificity and the site selectivity of X-ray absorption spectroscopy with the aid of ab initio quantum-mechanical and molecular-mechanics calculations, we show how, in addition to the proton transfer, the subsequent rearrangement of the urea dimer and the associated change of the electronic structure can be identified with site selectivity. These results establish the considerable potential of flat-jet, table-top X-ray absorption spectroscopy7,8 in elucidating solution-phase ultrafast dynamics in biomolecular systems.

Polysaccharide from aerial part of Chuanminshen violaceum alleviates oxidative stress and inflammatory response in aging mice through modulating intestinal microbiota.

Aging is a biological process of progressive deterioration of physiological functions, which poses a serious threat to individual health and a heavy burden on public health systems. As population aging continues, research into anti-aging drugs that prolong life and improve health is of particular importance. In this study, the polysaccharide from stems and leaves of Chuanminshen violaceum was obtained with water extraction and alcohol precipitation, and then separated and purified with DEAE anion exchange chromatography and gel filtration to obtain CVP-AP-I. We gavaged natural aging mice with CVP-AP-I and performed serum biochemical analysis, histological staining, quantitative real-time PCR (qRT-PCR) and ELISA kit assays to analyze inflammation and oxidative stress-related gene and protein expression in tissues, and 16SrRNA to analyze intestinal flora. We found that CVP-AP-I significantly improved oxidative stress and inflammatory responses of the intestine and liver, restored the intestinal immune barrier, and balanced the dysbiosis of intestinal flora. In addition, we revealed the potential mechanism behind CVP-AP-I to improve intestinal and liver function by regulating intestinal flora balance and repairing the intestinal immune barrier to regulate the intestinal-liver axis. Our results indicated that C. violaceum polysaccharides possessed favorable antioxidant, anti-inflammatory and potentially anti-aging effects in vivo.

Angelica sinensis aboveground part polysaccharide and its metabolite 5-MT ameliorate colitis via modulating gut microbiota and TLR4/MyD88/NF-κB pathway.

The roots of Angelica sinensis have been used in Traditional Chinese Medicine for thousands of years. However, tons of aerial parts of this herb (aboveground part) are commonly discarded during the process of root preparations. A polysaccharide (ASP-Ag-AP) in the aboveground parts of A. sinensis was isolated and preliminarily characterized as typical plant pectin. ASP-Ag-AP exhibited noticeable protective effects against dextran sodium sulfate (DSS)-induced colitis, including reduction of colonic inflammation, modulation of barrier function, and alteration of gut microbiota and serum metabolite profile. Anti-inflammatory effects of ASP-Ag-AP were observed by inhibiting TLR4/MyD88/NF-κB signaling pathway in vitro and in vivo. Additionally, the level of serum metabolite 5-methyl-dl-tryptophan (5-MT) was reduced by DSS and restored by ASP-Ag-AP, which also negatively correlated with Bacteroides, Alistipes, Staphylococcus and pro-inflammatory factors. The protection from inflammatory stress on intestinal porcine enterocytes cells (IPEC-J2) of 5-MT was observed through the inhibition of TLR4/MyD88/NF-κB pathway. Besides, 5-MT also exhibited robust anti-inflammatory effect in colitis mice with improving colitis symptoms, barrier function and gut microbiota, which was the same as presented by ASP-Ag-AP. Therefore, ASP-Ag-AP could be a promising agent for colitis prevention and 5-MT could be the signal metabolite of ASP-Ag-AP on defending against intestinal inflammatory stress.