Single-cell omics identifies inflammatory signaling as a trans-differentiation trigger in mouse embryos.

Trans-differentiation represents a direct lineage conversion; however, insufficient characterization of this process hinders its potential applications. Here, to explore a potential universal principal for trans-differentiation, we performed single-cell transcriptomic analysis of endothelial-to-hematopoietic transition (EHT), endothelial-to-mesenchymal transition, and epithelial-to-mesenchymal transition in mouse embryos. We applied three scoring indexes of entropies, cell-type signature transcription factor expression, and critical transition signals to show common features underpinning the fate plasticity of transition states. Cross-model comparison identified inflammatory-featured transition states and a common trigger role of interleukin-33 in promoting fate conversions. Multimodal profiling (integrative transcriptomic and chromatin accessibility analysis) demonstrated the inflammatory regulation of hematopoietic specification. Furthermore, multimodal omics and fate-mapping analyses showed that endothelium-specific Spi1, as an inflammatory effector, governs appropriate chromatin accessibility and transcriptional programs to safeguard EHT. Overall, our study employs single-cell omics to identify critical transition states/signals and the common trigger role of inflammatory signaling in developmental-stress-induced fate conversions.

p16High senescence restricts cellular plasticity during somatic cell reprogramming.

Despite advances in four-factor (4F)-induced reprogramming (4FR) in vitro and in vivo, how 4FR interconnects with senescence remains largely under investigated. Here, using genetic and chemical approaches to manipulate senescent cells, we show that removal of p16High cells resulted in the 4FR of somatic cells into totipotent-like stem cells. These cells expressed markers of both pluripotency and the two-cell embryonic state, readily formed implantation-competent blastoids and, following morula aggregation, contributed to embryonic and extraembryonic lineages. We identified senescence-dependent regulation of nicotinamide N-methyltransferase as a key mechanism controlling the S-adenosyl-L-methionine levels during 4FR that was required for expression of the two-cell genes and acquisition of an extraembryonic potential. Importantly, a partial 4F epigenetic reprogramming in old mice was able to reverse several markers of liver aging only in conjunction with the depletion of p16High cells. Our results show that the presence of p16High senescent cells limits cell plasticity, whereas their depletion can promote a totipotent-like state and histopathological tissue rejuvenation during 4F reprogramming.

Identification of HSC/MPP expansion units in fetal liver by single-cell spatiotemporal transcriptomics.

Limited knowledge of cellular and molecular mechanisms underlying hematopoietic stem cell and multipotent progenitor (HSC/MPP) expansion within their native niche has impeded the application of stem cell-based therapies for hematological malignancies. Here, we constructed a spatiotemporal transcriptome map of mouse fetal liver (FL) as a platform for hypothesis generation and subsequent experimental validation of novel regulatory mechanisms. Single-cell transcriptomics revealed three transcriptionally heterogeneous HSC/MPP subsets, among which a CD93-enriched subset exhibited enhanced stem cell properties. Moreover, by employing integrative analysis of single-cell and spatial transcriptomics, we identified novel HSC/MPP 'pocket-like' units (HSC PLUS), composed of niche cells (hepatoblasts, stromal cells, endothelial cells, and macrophages) and enriched with growth factors. Unexpectedly, macrophages showed an 11-fold enrichment in the HSC PLUS. Functionally, macrophage-HSC/MPP co-culture assay and candidate molecule testing, respectively, validated the supportive role of macrophages and growth factors (MDK, PTN, and IGFBP5) in HSC/MPP expansion. Finally, cross-species analysis and functional validation showed conserved cell-cell interactions and expansion mechanisms but divergent transcriptome signatures between mouse and human FL HSCs/MPPs. Taken together, these results provide an essential resource for understanding HSC/MPP development in FL, and novel insight into functional HSC/MPP expansion ex vivo.

De novo generation of macrophage from placenta-derived hemogenic endothelium.

Macrophages play pivotal roles in immunity, hematopoiesis, and tissue homeostasis. In mammals, macrophages have been shown to originate from yolk-sac-derived erythro-myeloid progenitors and aorta-gonad-mesonephros (AGM)-derived hematopoietic stem cells. However, whether macrophages can arise from other embryonic sites remains unclear. Here, using single-cell RNA sequencing, we profile the transcriptional landscape of mouse fetal placental hematopoiesis. We uncover and experimentally validate that a CD44+ subpopulation of placental endothelial cells (ECs) exhibits hemogenic potential. Importantly, lineage tracing using the newly generated Hoxa13 reporter line shows that Hoxa13-labeled ECs can produce placental macrophages, named Hofbauer cell (HBC)-like cells. Furthermore, we identify two subtypes of HBC-like cells, and cell-cell interaction analysis identifies their potential roles in angiogenesis and antigen presentation, separately. Our study provides a comprehensive understanding of placental hematopoiesis and highlights the placenta as a source of macrophages, which has important implications for both basic and translational research.

Reversed-engineered human alveolar lung-on-a-chip model.

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.

[Correlations between content of linarin in Chrysanthemum indicum and climatic factors in habitats].

Chrysanthemi Indici Flos(CIF), the capitulum of Chrysanthemum indicum, is widely used in proprietary Chinese medicine and daily chemical products. At present, CIF is mainly produced from wild resources and rarely cultivated. This study aims to reveal the correlations between linarin content in CIF and climatic factors in different habitats, and provide a theoretical basis for suitable zoning and rational production of medicinal materials. The content of linarin in CIF was determined by HPLC. Grey relational analysis and Pearson correlation analysis were carried out for linarin content with climatic factors. The results showed that the content of linarin in CIF was significantly different among different habitats. The grey relational degrees of climatic factors with linarin content was in an order of average annual precipitation>annual average sunshine hours>annual average temperature>longitude>annual frost-free period>latitude>altitude. Longitude, annual average temperature and average annual precipitation had significantly positive correlations with the content of linarin in CIF, whereas latitude and altitude showed negative correlations with it. The annual frost-free period and annual average sunshine hours had no significant correlation with the content of linarin in CIF. The content of linarin in CIF varied significantly in different habitats. High longitude, low latitude, low altitude, high annual average temperature and high annual average precipitation could be used as indicators for the habitats of high-quality Ch. indicum. This study provides a reference for selecting suitable producing areas of Ch. indicum and establishing artificial cultivation system.

A single-cell resolution developmental atlas of hematopoietic stem and progenitor cell expansion in zebrafish.

During vertebrate embryogenesis, fetal hematopoietic stem and progenitor cells (HSPCs) exhibit expansion and differentiation properties in a supportive hematopoietic niche. To profile the developmental landscape of fetal HSPCs and their local niche, here, using single-cell RNA-sequencing, we deciphered a dynamic atlas covering 28,777 cells and 9 major cell types (23 clusters) of zebrafish caudal hematopoietic tissue (CHT). We characterized four heterogeneous HSPCs with distinct lineage priming and metabolic gene signatures. Furthermore, we investigated the regulatory mechanism of CHT niche components for HSPC development, with a focus on the transcription factors and ligand-receptor networks involved in HSPC expansion. Importantly, we identified an endothelial cell-specific G protein-coupled receptor 182, followed by in vivo and in vitro functional validation of its evolutionally conserved role in supporting HSPC expansion in zebrafish and mice. Finally, comparison between zebrafish CHT and human fetal liver highlighted the conservation and divergence across evolution. These findings enhance our understanding of the regulatory mechanism underlying hematopoietic niche for HSPC expansion in vivo and provide insights into improving protocols for HSPC expansion in vitro.

Smarca5-mediated epigenetic programming facilitates fetal HSPC development in vertebrates.

Nascent hematopoietic stem and progenitor cells (HSPCs) acquire definitive hematopoietic characteristics only when they develop into fetal HSPCs; however, the mechanisms underlying fetal HSPC development are poorly understood. Here, we profiled the chromatin accessibility and transcriptional features of zebrafish nascent and fetal HSPCs using ATAC-seq and RNA-seq and revealed dynamic changes during HSPC transition. Functional assays demonstrated that chromatin remodeler-mediated epigenetic programming facilitates fetal HSPC development in vertebrates. Systematical screening of chromatin remodeler-related genes identified that smarca5 is responsible for the maintenance of chromatin accessibility at promoters of hematopoiesis-related genes in fetal HSPCs. Mechanistically, Smarca5 interacts with nucleolin to promote chromatin remodeling, thereby facilitating genomic binding of transcription factors to regulate expression of hematopoietic regulators such as bcl11ab. Our results unravel a new role of epigenetic regulation and reveal that Smarca5-mediated epigenetic programming is responsible for fetal HSPC development, which will provide new insights into the generation of functional HSPCs both in vivo and in vitro.

Copper nanoparticle decorated non-woven polypropylene fabrics with durable superhydrophobicity and conductivity.

In this study, a facile method was prepared to fabricate highly flexible, conductive and superhydrophobic polymer fabrics. Copper nanoparticles (CuNPs) were decorated on polypropylene fabrics using a simple spraying method and superhydrophobicity was obtained after vacuum drying for 4 h without any surface modifier. Accumulation of CuNPs constituted coral-like rough micro-nano structures, forming a stable Cassie model and endowing the surface with dense charge transport pathways, thus resulting in excellent superhydrophobicity (water contact angle ∼159°, sliding angle ∼2.3°) and conductivity (sheet resistance ∼0.92 Ω sq-1). The fabrics displayed superior waterproof and self-cleaning properties, as well as great sustainability in the water. Additionally, the superhydrophobicity and conductivity can be almost maintained after heat treatment, wear testing, water droplet impinging, weak alkali/acid treatment and repeated bending-kneading tests. These superhydrophobic and conductive fabrics that are free from moisture and pollution can be a reliable candidate to solve the water-penetration issue in the rapid development of flexible electronics.

High-T c Cooper-pair injection in a semiconductor-superconductor structure.

We observe Andreev reflection in a YBCO-GaN junction through differential conductance spectroscopy. A strong characteristic zero-bias peak was observed and persisted up to the critical temperature of the superconductor with a smaller superconducting order parameter Δ âˆ¼ 1 meV. The presence of Andreev reflection with the small Δ in comparison to its value for high-T c superconductors forms an important milestone toward demonstration of superconducting proximity in high-T c/semiconductor junctions. Experimental results were then compared to the theoretical model with good agreement. Efficient injection of Cooper pairs into direct bandgap semiconducting structures, together with high transition temperature of YBCO, can pave the way to novel optoelectronics and quantum optical studies of high-T c materials.

An in situ electrical transport measurement system under ultra-high vacuum.

Low-dimensional materials exhibit exotic properties and have attracted widespread attention. However, many low-dimensional materials are highly sensitive to air, making it challenging to investigate their intrinsic properties with ex situ measurements. To overcome such challenges, here, we developed a system combined with sample growth, electrode deposition, and in situ electrical transport measurement under ultra-high vacuum condition. The in situ deposition of electrodes enables desired ohmic electrical contacts between the probes and samples, which allows continuous temperature dependent resistance (R-T) measurements. Combined with a scanning tunneling microscope, surface morphology, electronic structure, and electrical transport properties of the same sample can be systematically investigated. We demonstrate the performance of this in situ electrical transport measurement system with three-unit-cell thick FeSe films grown on Nb-doped SrTiO3(001) substrates, where a low-noise R-T curve with a zero-resistance superconducting transition temperature of ∼30 K is observed.

Characterization and Properties of Mg-xGd-1.5Nd-0.5Zn-0.5Zr Alloys for Biodegradation Applications.

The differences in microstructural characteristics, mechanical properties, and corrosion behavior of the as-cast and solution-treated Mg-xGd-1.5Nd-0.5Zn-0.5Zr alloys (Mg-xGd, x = 1, 3, and 5) were studied and discussed. The as-cast Mg-xGd alloys mainly consisted of an α-Mg and island-like eutectic (Mg,Zn)3RE phase, a few cuboidal phases (REH2), and a ZnZr phase. With the increase of Gd content, the grain sizes of the as-cast Mg-xGd alloys decreased. Compared to the microstructure of the as-cast Mg-xGd alloys, the eutectic (Mg,Zn)3RE phase disappeared and the cuboidal REH2 phases existed in the solution-treated Mg-xGd alloys. A large amount of ZnZrx phase was precipitated from α-Mg in the Mg-3Gd alloy and demonstrates a flower-like distribution. The ultimate tensile strength (UTS) and yield strength (YS) of the solution-treated Mg-xGd alloys increased with an increasing Gd content, with the UTS and YS of the Mg-5Gd alloys reaching 217.5 and 125.2 MPa, respectively. Immersion and electrochemical tests showed that the as-cast Mg-3Gd alloy presented the best corrosion resistance with a corrosion rate of 0.285 mm/yr. The corrosion resistance of the solution-treated Mg-3Gd alloy attained the lowest value (0.973 mm/yr), due to the large quantities of ZnZrx with a flower-like phase distribution, forming series of galvanic couple groups with the α-Mg.

Preparation and conductive property of Cu coatings and Cu-graphene composite coatings on ABS substrate.

A facile, low-cost and environmentally-friendly technique has been developed to prepare highly conductive copper-graphene nanosheet (Cu-GNS) composite coatings on ABS (Acrylonitrile-Butadiene-Styrene) substrate. The surface activation of ABS substrate was obtained by a chrome-free and palladium-free pretreatment consisting of molecular bonding. Before electroplating Cu, the homogeneous single Ag film on ABS surface was achieved by the electroless spray-plating process. In addition, the deposition of Cu and GNS increased in the coatings along with the current density increasing. Four-point-probe test confirmed that the resistivity of Cu coatings (0.08 mΩ mm) and Cu-GNS composite coatings (0.05 mΩ mm) was in the same order of magnitude as pure copper (0.0175 mΩ mm) at high current density. Meanwhile, comparing with the Cu coatings, the resistivity of Cu-GNS composite coatings was reduced by nearly 40% at the same current density. The conductive property was significantly improved owing to the deposition of GNS. Therefore, this work was expected to expand the method of polymer materials surface metallization.

Interfacial nanoconnections and enhanced mechanistic studies of metallic coatings for molecular gluing on polymer surfaces.

Interfacial adhesion has been identified as being key for realizing flexible devices. Here, strong interfacial nanoconnections involving metallic patterns on polymer surfaces were fabricated via a molecular bonding approach, which includes UV-assisted grafting and molecular self-assembly. The interfacial characteristics of conductive patterns on liquid crystal polymer substrates were observed via transmission electron microscopy and atomic force microscopy infrared spectroscopy. The interfacial molecular layers have a thickness of 10 nm. Due to the successful molecular bonding modifications, interfacial adhesion has been sufficiently improved; in particular, the peel-related breakage sites will be located in the modified layers on the plastic surface beneath the interface after the metallic coatings are peeled off. Integrating X-ray photoelectron spectroscopy, infrared spectroscopy, and scanning electron microscopy results, the molecular bonding mechanism has been revealed: UV-assisted grafting and self-assembly result in the construction of interfacial molecular architectures, which provide nanosized connecting bridges between the metallic patterns and polymer surfaces. Such in-depth interfacial studies can offer insight into interfacial adhesion, which will impact on the development of metal/polymer composite systems and continue to push the improvement of flexible devices.

Downregulation of serum exosomal miR-150-5p is associated with poor prognosis in patients with colorectal cancer.

Growing evidence have revealed the serum exosomal miRNAs emerged as biomarkers for various cancer types, including colorectal cancer (CRC). Here, we sought to explore the potential clinical significance of serum exosomal miR-150-5p in CRC. A total of 133 CRC patients and 60 healthy volunteers as control group were recruited in this study. Exosomes were isolated from the serum of all the participants. The total RNA was isolated from the exosomes and the serum exosomal miR-150-5p levels were measured by quantitative reverse transcription-polymerase chain reaction. The findings showed that the serum exosomal miR-150-5p levels were significantly reduced in CRC cases compared with those in the control group. Serum exosomal miR-150-5p levels in post-operative blood samples were greatly upregulated one month after surgical treatment. In addition, decreased serum exosomal miR-150-5p expression was closely correlated with poorly differentiation, positive lymph node metastasis and advanced TNM stage. Moreover, receiver operating characteristic (ROC) curve analysis showed serum exosomal miR-150-5p level had good performance to identify CRC cases from healthy volunteers, and a combination of serum exosomal miR-150-5p and carcinoembryonic antigen (CEA) could improve the diagnostic accuracy with an increased the area under the ROC curve (AUC) value. Furthermore, the survival time of patients with higher serum exosomal miR-150-5p expression was significantly longer than those with lower expression. Serum exosomal miR-150-5p was confirmed as an independent prognostic indicator in CRC. Mechanistically, ZEB1 was identified as a direct downstream target of miR-150-5p. Collectively, serum exosomal miR-150-5p might be a novel noninvasive biomarker for CRC diagnosis and prognosis.

Preparation of Ag/graphene composite films by three-component spray-spin-spray coating on surface modified PET substrate.

We report a novel method of three-component spray-spin-spray coating to prepare uniform and dense Ag/graphene nanosheet (Ag/GNS) composite films on a surface modified polyethylene terephthalate (PET) substrate. Compared with an untreated sample, the adhesion between composite films and the substrate was significantly enhanced due to the effects of chemical etching and molecular grafting. From the results of the four-probe test, the sheet resistance of hybrid films of Ag/GNS-5 reduced by 60% compared to the pristine Ag films, which was due to the efficient deposition of GNS by spray-spin-spray coating method. Meanwhile, a variety of complex flexible patterns were successfully fabricated with the help of the masking method. This means that the method could provide an efficient and low cost way for flexible electronics production of various complex flexible metallic coatings in practice.

Corrosion mechanism of the as-cast and as-extruded biodegradable Mg-3.0Gd-2.7Zn-0.4Zr-0.1Mn alloys.

Electrochemical measurements and immersion tests were adopted to investigate corrosion mechanism of the as-cast and as-extruded Mg-3.0Gd-2.7Zn-0.4Zr-0.1Mn (GZKM-1) alloys. Results of immersion tests indicate that corrosion resistance of the as-extruded GZKM-1 alloy is better. Galvanic corrosion between α-Mg matrix and ß-(MgZn)3Gd compounds is the main corrosion mechanism of the two GZKM-1 alloys. Larger α-Mg peeled off from the as-cast samples, then expanded corrosion reaction along discontinuous ß-(MgZn)3Gd compounds making a pit corrosion phenomenon in macro view. Granular ß-(MgZn)3Gd or precipitations fell off from the as-extruded samples, and then expanded corrosion reaction along the concentration of the particle ß-(MgZn)3Gd (and/or precipitations). Most areas of the as-extruded alloy are protected well by denser protective oxidation film.

Two-component spin-coated Ag/CNT composite films based on a silver heterogeneous nucleation mechanism adhesion-enhanced by mechanical interlocking and chemical grafting.

In this paper, a new method for the synthesis of silver carbon nanotube (Ag/CNT) composite films as conductive connection units for flexible electronic devices is presented. This method is about a two-component solution process by spin coating with an after-treatment annealing process. In this method, multi-walled carbon nanotubes (MWCNTs) act as the core of silver heterogeneous nucleation, which can be observed and analyzed by a field-emission scanning electron microscope. With the effects of mechanical interlocking, chemical grafting, and annealing, the interfacial adhesive strength between films and PET sheets was enhanced to 12 N cm-1. The tensile strength of the Ag/CNT composite films was observed to increase by 38% by adding 5 g l-1 MWCNTs. In the four-probe method, the resistivity of Ag/CNT-5 declined by 78.2% compared with pristine Ag films. The anti-fatigue performance of the Ag/CNT composite films was monitored by cyclic bending deformation and the results revealed that the growth rate of electrical resistance during the deformation was obviously retarded. As for industrial application, this method provides an efficient low-cost way to prepare Ag/CNT composite films and can be further applied to other coating systems.

Mechanical properties and biocorrosion resistance of the Mg-Gd-Nd-Zn-Zr alloy processed by equal channel angular pressing.

A Mg-Gd-Nd-Zn-Zr alloy was processed by equal channel angular pressing (ECAP) at 375°C. The grain size of Mg-Gd-Nd-Zn-Zr alloy was refined to ~2.5µm with the spherical precipitates (ß1 phase) distributing in the matrix. The mechanical properties of ECAPed alloy were significantly improved as a result of the grain refinement and precipitation strengthening. The corrosion rate of the ECAPed magnesium alloy in simulated body fluid dramatically decreased from 0.236mm/a to 0.126mm/a due to the strong basal texture and refined microstructure. This wrought magnesium alloy shows potentials in biomedical application.