Sulfated oligosaccharide activates endothelial Notch for inducing macrophage-associated arteriogenesis to treat ischemic diseases.

Ischemic diseases lead to considerable morbidity and mortality, yet conventional clinical treatment strategies for therapeutic angiogenesis fall short of being impactful. Despite the potential of biomaterials to deliver pro-angiogenic molecules at the infarct site to induce angiogenesis, their efficacy has been impeded by aberrant vascular activation and off-target circulation. Here, we present a semisynthetic low-molecular sulfated chitosan oligosaccharide (SCOS) that efficiently induces therapeutic arteriogenesis with a spontaneous generation of collateral circulation and blood reperfusion in rodent models of hind limb ischemia and myocardial infarction. SCOS elicits anti-inflammatory macrophages' (Mφs') differentiation into perivascular Mφs, which in turn directs artery formation via a cell-to-cell communication rather than secretory factor regulation. SCOS-mediated arteriogenesis requires a canonical Notch signaling pathway in Mφs via the glycosylation of protein O-glucosyltransferases 2, which results in promoting arterial differentiation and tissue repair in ischemia. Thus, this highly bioactive oligosaccharide can be harnessed to direct efficiently therapeutic arteriogenesis and perfusion for the treatment of ischemic diseases.

MATR3-antisense LINE1 RNA meshwork scaffolds higher-order chromatin organization.

Long interspersed nuclear elements (LINEs) play essential roles in shaping chromatin states, while the factors that cooperate with LINEs and their roles in higher-order chromatin organization remain poorly understood. Here, we show that MATR3, a nuclear matrix protein, interplays with antisense LINE1 (AS L1) RNAs to form a meshwork via phase separation, providing a dynamic platform for chromatin spatial organization. MATR3 and AS L1 RNAs affect the nuclear localization of each other. After MATR3 depletion, the chromatin, particularly H3K27me3-modified chromatin, redistributes in the cell nuclei. Topologically associating domains (TADs) that highly transcribe MATR3-associated AS L1 RNAs show decreased intra-TAD interactions in both AML12 and ES cells. MATR3 depletion increases the accessibility of H3K27me3 domains adjacent to MATR3-associated AS L1, without affecting H3K27me3 modifications. Furthermore, amyotrophic lateral sclerosis (ALS)-associated MATR3 mutants alter biophysical features of the MATR3-AS L1 RNA meshwork and cause an abnormal H3K27me3 staining. Collectively, we reveal a role of the meshwork formed by MATR3 and AS L1 RNAs in gathering chromatin in the nucleus.

Harnessing matrix stiffness to engineer a bone marrow niche for hematopoietic stem cell rejuvenation.

Hematopoietic stem cell (HSC) self-renewal and aging are tightly regulated by paracrine factors from the bone marrow niche. However, whether HSC rejuvenation could be achieved by engineering a bone marrow niche ex vivo remains unknown. Here, we show that matrix stiffness fine-tunes HSC niche factor expression by bone marrow stromal cells (BMSCs). Increased stiffness activates Yap/Taz signaling to promote BMSC expansion upon 2D culture, which is largely reversed by 3D culture in soft gelatin methacrylate hydrogels. Notably, 3D co-culture with BMSCs promotes HSC maintenance and lymphopoiesis, reverses aging hallmarks of HSCs, and restores their long-term multilineage reconstitution capacity. In situ atomic force microscopy analysis reveals that mouse bone marrow stiffens with age, which correlates with a compromised HSC niche. Taken together, this study highlights the biomechanical regulation of the HSC niche by BMSCs, which could be harnessed to engineer a soft bone marrow niche for HSC rejuvenation.

Engineering Neutrophil Immunomodulatory Hydrogels Promoted Angiogenesis.

Timely restoration of blood supply following ischemia is critical to rescue damaged tissue. However, clinical efficacy is hampered by the inflammatory response after ischemia. Whether inflammation fine tunes the angiogenesis and the function of blood vessels via the heterogeneity of neutrophils remain poorly understood. Herein, the objective of this work is to incorporate the growth factors secreted by neutrophils into a porous gelatin methacrylate (GelMA) hydrogel, which subsequently is used as a novel regenerative scaffold with defined architecture for ischemia. We demonstrate that anti-inflammatory neutrophils (N2-polarized neutrophils) play an important role in promoting the migration of human umbilical vein endothelial cells (HUVECs) and formation of capillary-like networks in vitro. More importantly, vascular anastomosis can be achieved by modulating the neutrophils to N2 phenotype. In addition, N2-polarized composite hydrogel scaffolds can regulate inflammation, maintain the survival of exogenous cells, and promote angiogenesis in vivo. Notably, the composite hydrogel scaffolds promote neovascularization during exogenous introduction of endothelial cells by anastomosis. Taken together, this study highlights N2-polarized neutrophils composite hydrogels can achieve vascularization rapidly by regulating inflammation and promoting vascular anastomosis. This work lays the foundation for research into the treatment of ischemia and may inspire further research into novel treatment options.

Selective Semihydrogenation of Polarized Alkynes by a Gold Hydride Nanocluster.

The hydridic hydrogen in nanogold catalysts has long been postulated as an important intermediate in hydrogenation reactions, but it has not been directly observed. Here, we report the synthesis of a new undecagold cluster with a bidentate phosphine ligand. The chelating effects of the bidentate ligand result in a more symmetric Au11 core with two labile Cl- ligands that can exchange with BH4-, leading to a novel undecagold hydride cluster. The new hydride cluster is discovered to readily undergo hydroauration reaction with alkynes containing electron-withdrawing groups, forming key gold-alkenyl semihydrogenation intermediates, which can be efficiently and selectively converted to Z-alkenes under acidic conditions. All key reaction intermediates are isolated and characterized, providing atomic-level insights into the active sites and mechanisms of semihydrogenation reactions catalyzed by gold-based nanomaterials. The hydridic hydrogen in the undecagold cluster is found to be the key to prevent over hydrogenation of alkenes to alkanes. The current study provides fundamental insights into hydrogenation chemistry enabled by gold-based nanomaterials and may lead to the development of efficient catalysts for selective semihydrogenation or functionalization of alkynes.

A Heteroleptic Gold Hydride Nanocluster for Efficient and Selective Electrocatalytic Reduction of CO2 to CO.

It has been a long-standing challenge to create and identify the active sites of heterogeneous catalysts, because it is difficult to precisely control the interfacial chemistry at the molecular level. Here we report the synthesis and catalysis of a heteroleptic gold trihydride nanocluster, [Au22H3(dppe)3(PPh3)8]3+ [dppe = 1,2-bis(diphenylphosphino)ethane, PPh3 = triphenylphosphine]. The Au22H3 core consists of two Au11 units bonded via six uncoordinated Au sites. The three H atoms bridge the six uncoordinated Au atoms and are found to play a key role in catalyzing electrochemical reduction of CO2 to CO with a 92.7% Faradaic efficiency (FE) at -0.6 V (vs RHE) and high reaction activity (134 A/gAu mass activity). The CO current density and FECO remained nearly constant for the CO2 reduction reaction for more than 10 h, indicating remarkable stability of the Au22H3 catalyst. The Au22H3 catalytic performance is among the best Au-based catalysts reported thus far for electrochemical reduction of CO2. Density functional theory (DFT) calculations suggest that the hydride coordinated Au sites are the active centers, which facilitate the formation of the key *COOH intermediate.

The synthesis and characterization of a new diphosphine-protected gold hydride nanocluster.

Gold is the most inert metal and does not form a bulk hydride. However, gold becomes chemically active in the nanometer scale and gold nanoparticles have been found to exhibit important catalytic properties. Here, we report the synthesis and characterization of a highly stable ligand-protected gold hydride nanocluster, [Au22H3(dppee)7]3+ [dppee = bis(2-diphenylphosphino) ethyl ether]. A synthetic method is developed to obtain high purity samples of the gold trihydride nanocluster with good yields. The properties of the new hydride cluster are characterized with different experimental techniques, as well as theoretical calculations. Solid samples of [Au22H3(dppee)7]3+ are found to be stable under ambient conditions. Both experimental evidence and theoretical evidence suggest that the Au22H3 core of the [Au22H3(dppee)7]3+ hydride nanocluster consists of two Au11 units bonded via two triangular faces, creating six uncoordinated Au sites at the interface. The three H atoms bridge the six uncoordinated Au atoms at the interface. The Au11 unit behaves as an eight-electron trivalent superatom, forming a superatom triple bond (Au11 ≡ Au11) in the [Au22H3(dppee)7]3+ trihydride nanocluster assisted by the three bridging H atoms.

Sulfated polysaccharide directs therapeutic angiogenesis via endogenous VEGF secretion of macrophages.

Notwithstanding the remarkable progress in the clinical treatment of ischemic disease, proangiogenic drugs mostly suffer from their abnormal angiogenesis and potential cancer risk, and currently, no off-the-shelf biomaterials can efficiently induce angiogenesis. Here, we reported that a semisynthetic sulfated chitosan (SCS) readily engaged anti-inflammatory macrophages and increased its secretion of endogenous vascular endothelial growth factor (VEGF) to induce angiogenesis in ischemia via a VEGF-VEGFR2 signaling pathway. The depletion of host macrophages abrogated VEGF secretion and vascularization in implants, and the inhibition of VEGF or VEGFR2 signaling also disrupted the macrophage-associated angiogenesis. In addition, in a macrophage-inhibited mouse model, SCS efficiently helped to recover the endogenous levels of VEGF and the number of CD31hiEmcnhi vessels in ischemia. Thus, both sulfated group and pentasaccharide sequence in SCS played an important role in directing the therapeutic angiogenesis, indicating that this highly bioactive biomaterial can be harnessed to treat ischemic disease.

The Synthesis, Bonding, and Transformation of a Ligand-Protected Gold Nanohydride Cluster.

Gold does not react with H2 to form bulk hydrides. Here we report the synthesis and characterization of a gold nanohydride protected by diphosphine ligands, [Au22 H4 (dppo)6 ]2+ [dppo=1,8-bis(diphenylphosphino)octane]. The Au22 core consists of two Au11 units bonded by eight Au atoms not coordinated by the diphosphine ligands. The four H atoms are found to bridge the eight uncoordinated Au atoms at the interface. Each Au11 unit can be viewed as a tetravalent superatom forming four delocalized Au-H-Au bonds, similar to the quadruple bond first discovered in the [Re2 Cl8 ]2- inorganic cluster. The [Au22 H4 (dppo)6 ]2+ nanohydride is found to lose H atoms over an extended time via H evolution (H2 ), proton (H+ ) and hydride (H- ) releases. This complete repertoire of H-related transformations suggests that the [Au22 H4 (dppo)6 ]2+ nanohydride is a versatile model catalyst for understanding the mechanisms of chemical reactions involving hydrogen on the surface of gold nanoparticles.

A universal growth strategy for DNA-programmed quantum dots on graphene oxide surfaces.

The emerging materials of semiconductor quantum dots/graphene oxide (QDs/GO) hybrid composites have recently attracted intensive attention in materials science and technology due to their potential applications in electronic and photonic devices. Here, a simple and universal strategy to produce DNA-programmed semiconductor quantum dots/graphene oxide (QDs/GO) hybrid composites with controllable sizes, shapes, compositions, and surface properties is reported. This proof-of-concept work successfully demonstrates the use of sulfhydryl modified single-stranded DNA (S-ssDNA) as a 'universal glue' which can adsorb onto GO easily and provide the growth sites to synthesize CdS QDs, CdSe QDs, CdTe QDs and CdTeSe QDs with distinctive sizes, shapes and properties. Also, adapting this method, other graphene oxide-based hybrid materials which are easily synthesized in aqueous solution, including oxides, core-shell structure QDs and metal nanocrystals, would be possible. This method provided a universal strategy for the synthesis and functional realization of graphene -based nanomaterials.

Halogen effects on the electronic and optical properties of Au13 nanoclusters.

We report an experimental and theoretical investigation of the electronic and optical properties of a series of icosahedral Au13 nanoclusters, protected using different halogen ligands (Cl, Br, and I), as well as 1,2-bis(diphenylphosphino)ethane (dppe) ligands. All three clusters are comprised of the same Au13 kernel with two halogens coordinated to the poles of the icosahedral cluster along with five dppe ligands. UV-vis absorption spectra indicate a systematic red shift from Cl to Br to I, as well as a sudden enhancement of the second excitonic peak for the I-coordinated cluster. Density functional theory (DFT) calculations suggest that all clusters possess a wide HOMO-LUMO energy gap of ∼1.79 eV and are used to assign the first two excitonic bands. Frontier orbital analyses reveal several HOMO → LUMO transitions involving halogen-to-metal charge transfers. For the I-coordinated cluster, more complicated I-to-metal charge transfers give rise to different excitation features observed experimentally. The current findings show that halogen ligands play important roles in the electronic structures of gold clusters and can be utilized to tune the optical properties of the clusters.

Forensic drowning site inference employing mixed pyrosequencing profile of DNA barcode gene (rbcL).

The development of DNA barcoding method has given rise to a promising way of studying genetic taxonomy. Our previous study showed that pyrosequencing profile of 18S rDNA V7 hypervariable region can be used for identifying water sources without resolving the exact components of diatom colonies in water samples. In this continued study, we aimed to improve the established analysis method and to provide scientific evidence for forensic practices. A drowning animal model was set up by injecting mimic drowning fluid into the respiratory tract of the rabbit. In order to minimize the interference of animal DNA, the hypervariable region of chloroplast ribulose-1,5-bisphosphate carboxylase large unit gene (rbcL) was used as the pyrosequencing target region for the consistency analysis of plankton populations in tissues and water samples. After decoding the pyrosequencing profile of the targeted rbcL gene with the AdvISER-M-PYRO algorithm, the plankton colony that was inhaled into drowning animal lung tissue could be successfully traced back to the source of drowning fluid. Our data suggest that this method could be a reliable tool assisting forensic drowning site inference.

Highly Efficient Active All-Dielectric Metasurfaces Based on Hybrid Structures Integrated with Phase-Change Materials: From Terahertz to Optical Ranges.

Recently, all-dielectric metasurfaces (AMs) have emerged as a promising platform for high-efficiency devices ranging from the terahertz to optical ranges. However, active and fast tuning of their properties, such as amplitude, phase, and operating frequency, remains challenging. Here, a generic method is proposed for obtaining high-efficiency active AMs from the terahertz to optical ranges by using "hybrid structures" integrated with phase-change materials. Various phase-change mechanisms including metal-insulator phase change, nonvolatile phase change, and ferroelectric phase change are investigated. We first experimentally demonstrate several high-efficiency active AMs operating in the terahertz range based on hybrid structures composed of free-standing silicon microstructures covered with ultrathin phase-change nanofilms (thickness d ≪ λ). We show that both the frequencies and the strength of the Mie resonances can be efficiently tuned, resulting in unprecedented modulation depth. Furthermore, detailed analyses of available phase-change materials and their properties are provided to offer more options for active AMs. Finally, several feasible hybrid structures for active AMs in the optical range are proposed and confirmed numerically. The broad platform built in this work for active manipulation of waves from the terahertz to optical ranges may have numerous potential applications in optical devices including switches, modulators, and sensors.

Aptamer-DNA concatamer-quantum dots based electrochemical biosensing strategy for green and ultrasensitive detection of tumor cells via mercury-free anodic stripping voltammetry.

A electrochemical biosensing strategy was developed for green and ultrasensitive detection of tumor cells by combining aptamer-DNA concatamer-CdTe quantum dots (QDs) signal amplification probe with mercury-free anodic stripping voltammetry (ASV). First, aptamer-DNA concatamer- CdTe QDs probes were designed by DNA hybridization and covalent assembling, which contained specific recognition of aptamer and signal amplification incorporating the DNA concatamer with QDs. Meanwhile, the capture electrode, glassy carbon electrode (GCE)/Graphene oxide (GO)/Polyaniline (PANI) / Glutaraldehyde (GA) / concanavalin A (Con A) was fabricated by a layer-by-layer assembling technique. K562 cells, as model cancer cells were detected to demonstrate the feasibility of this sensing strategy. Then, novel composite, graphene (GR)- Poly diallyldimethylammonium chloride (PDDA)/L-Cysteine (L- Cys), was explored in ASV which replaced mercury electrodes using for determination of tumor cells. The proposed electrochemical biosensor showed high sensitivity with the detection limit of 60 cells mL-1. More importantly, this novel design of signal amplification probes and the exploration of new composites in mercury-free ASV analysis would provide a promising method for ultrasensitive biosensor preparation and green electrochemical detection of tumor cells.

Flexible and tunable terahertz all-dielectric metasurface composed of ceramic spheres embedded in ferroelectric/elastomer composite: erratum.

We report an error in our paper [Opt. Express 26, 11633 2018]. The SEM picture shown in Fig. 1(e)Fig. 1(a)-(d) The fabrication process of all-dielectric metasurface. (e) The scanning electron microscope (SEM) photograph of fabricated sample. was incorrect. This was due to an error during manuscript preparation: The SEM picture of control group is inadvertently provided in Fig. 1(e), instead of correct SEM picture of sample. Figures 1(a)-1(d) are correct and remain unchanged, and this error does not affect the results or conclusions of the paper. We apologize for any confusion this may have caused.

Potential forensic biogeographic application of diatom colony consistency analysis employing pyrosequencing profiles of the 18S rDNA V7 region.

Diatom examination has always been used for the diagnosis of drowning in forensic practice. However, traditional examination of the microscopic features of diatom frustules is time-consuming and requires taxonomic expertise. In this study, we demonstrate a potential DNA-based method of inferring suspected drowning site using pyrosequencing (PSQ) of the V7 region of 18S ribosome DNA (18S rDNA) as a diatom DNA barcode. By employing a sparse representation-based AdvISER-M-PYRO algorithm, the original PSQ signals of diatom DNA mixtures were deciphered to determine the corresponding taxa of the composite diatoms. Additionally, we evaluated the possibility of correlating water samples to collection sites by analyzing the PSQ signal profiles of diatom mixtures contained in the water samples via multidimensional scaling. The results suggest that diatomaceous PSQ profile analysis could be used as a cost-effective method to deduce the geographical origin of an environmental bio-sample.

Flexible and tunable terahertz all-dielectric metasurface composed of ceramic spheres embedded in ferroelectric/ elastomer composite.

Terahertz (THz) all-dielectric metasurfaces made of high-index and low-loss resonators have attracted more and more attention due to their versatile properties. However, the all-dielectric metasurfaces in THz suffer from limited bandwidth and low tunability. Meanwhile, they are usually fabricated on flat and rigid substrates, and consequently their applications are restricted. Here, a simple approach is proposed and experimentally demonstrated to obtain a flexible and tunable THz all-dielectric metasurface. In this metasurface, micro ceramic spheres (ZrO2) are embedded in a ferroelectric (strontium titanate) / elastomer (polydimethylsiloxane) composite. It is shown that the Mie resonances in micro ceramic spheres can be thermally and reversibly tuned resulting from the temperature dependent permittivity of the ferroelectric / PDMS composite. This metasurface characterized by flexibility and tunability is expected to have a more extensive application in active THz devices.

Forensic applicability of multi-allelic InDels with mononucleotide homopolymer structures.

Insertion/deletion polymorphisms (InDels), which possess the characteristics of low mutation rates and a short amplicon size, have been regarded as promising markers for forensic DNA analysis. InDels can be classified as bi-allelic or multi-allelic, depending on the number of alleles. Many studies have explored the use of bi-allelic InDels in forensic applications, such as individual identification and ancestry inference. However, multi-allelic InDels have received relatively little attention. In this study, InDels with 2-6 alleles and a minor allele frequency ≥0.01, in Chinese Southern Han (CHS), were retrieved from the 1000 Genomes Project Phase III. Based on the structural analysis of all retrieved InDels, 17 multi-allelic markers with mononucleotide homopolymer structures were selected and combined in one multiplex PCR reaction system. Sensitivity, species specificity and applicability in forensic case work of the multiplex were analyzed. A total of 218 unrelated individuals from a Chinese Han population were genotyped. The combined discriminatory power (CDP), the combined match probability (CMP) and the cumulative probability of exclusion (CPE) were 0.9999999999609, 3.91E-13 and 0.9956, respectively. The results demonstrated that this InDel multiplex panel was highly informative in the investigated population and most of the 26 populations of the 1000 Genomes Project. The data also suggested that multi-allelic InDel markers with monomeric base pair expansions are useful for forensic applications.

[Association of programmed cell death 1 (PDCD1) gene polymorphisms with colorectal cancer among Han Chinese population].

OBJECTIVE: To assess the association of programmed cell death 1 (PDCD1) gene polymorphisms with the susceptibility and/or progression of colorectal cancer. METHODS: A hospital-based case-control study was carried out, which recruited 426 colorectal cancer patients and 500 healthy individuals. Five single nucleotide polymorphisms, namely rs36084323, rs11568821, rs2227981, rs2227982 and rs10204525, were selected for the study and genotyped with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: The G allele of rs36084323 under a dominant model was associated with increased risk of advanced TNM staging of colorectal cancer progression (OR=1.59, 95%CI=1.02-2.48). Haplotypes G-G-C-T-A and A-G-C-C-G of the rs36084323, rs11568821, rs2227981, rs2227982, and rs10204525 were negatively associated with the occurrence of colorectal cancer. CONCLUSION: The G allele of rs36084323 is associated with increased risk of advanced TNM staging of colorectal cancer. Conversely, the incidence of colorectal cancer is negatively associated with the haplotypes G-G-C-T-A and A-G-C-C-G of rs36084323, rs11568821, rs2227981, rs2227982, and rs10204525.

Construction and forensic genetic characterization of 11 autosomal haplotypes consisting of 22 tri-allelic indels.

Insertion/deletion polymorphisms (indels), which combine the advantages of both short tandem repeats and single-nucleotide polymorphisms, are suitable for parentage testing. To overcome the limitations of the low polymorphism of di-allelic indels, we constructed a set of haplotypes with physically linked, multi-allelic indels. Candidate haplotypes were selected from the 1000 Genomes Project database, and were subject to the following criteria for inclusion: (i) each marker must have a minimum allele frequency (MAF) of ≥0.1 in the Han population of China; (ii) markers must exist in a non-coding region; (iii) the physical distance between a pair of candidate indels must be <500 bp; (iv) the allele length variation of each indel from 1 to 20 bp; (v) different haplotypes must be located on different chromosomes or chromosomal arms, or be more than 10 Mb apart if on the same chromosomal arm; and (vi) they must not be located across a recombination hotspot. A multiplex system with 11 haplotype markers, comprising 22 tri-allelic indel loci distributed over 10 chromosomes was developed. To validate the multiplex panel, we investigated the haplotype distribution in sets of two and three-generation pedigrees. The results demonstrated that the haplotypes consisting of multi-allelic indel markers exhibited higher polymorphism than a single indel locus, and thus provide Supplementary information for forensic kinship identification.