Topological insulators with unique edge states have revolutionized the understanding of solid-state materials. Recently, higher-order topological insulators (HOTIs), which host both gapped edge ...states and in-gap corner/hinge states, protected concurrently by band topology, were predicted and observed in experiments, unveiling a new horizon beyond the conventional bulk-edge correspondence. However, the control and manifestation of band topology in a hierarchy of dimensions, which is at the heart of HOTIs, have not yet been witnessed. Here, we propose theoretically and observe experimentally that tunable two-dimensional sonic crystals can be versatile systems to visualize and harness higher-order topology. In our systems, the two-dimensional acoustic bands mimic the quantum spin Hall effect, while the resultant one-dimensional helical edge states are gapped due to broken space-symmetry and carry quantized Zak phases, which then lead to zero-dimensional topological corner states. We demonstrate that topological transitions in the bulk and edges can be triggered independently by tuning the geometry of the sonic crystals. With complementary experiments and theories, our study reveals rich physics in HOTIs, opening a new route towards tunable topological metamaterials where novel applications, such as the topological transfer of acoustic energy among two-, one- and zero-dimensional modes, can be achieved.By tuning the geometry of a two-dimensional sonic crystal, its one-dimensional helical edge states become gapped and zero-dimensional topological corner states emerge. The band topology is thus manifested in a hierarchy of dimensions.
Weyl semimetals (WSMs)
exhibit phenomena such as Fermi arc surface states, pseudo-gauge fields and quantum anomalies that arise from topological band degeneracy in crystalline solids for electrons
...and metamaterials for photons
and phonons
. Here we report a higher-order Weyl semimetal (HOWSM) in a phononic system that exhibits topologically protected boundary states in multiple dimensions. We created the physical realization of the HOWSM in a chiral phononic crystal with uniaxial screw symmetry. Using acoustic pump-probe spectroscopies, we observed coexisting chiral Fermi arc states on two-dimensional surfaces and dispersive hinge arc states on one-dimensional hinge boundaries. These topological boundary states link the projections of the Weyl points (WPs) in different dimensions and directions, and hence demonstrate the higher-order topological physics
in WSMs. Our study further establishes the fundamental connection between higher-order topology and Weyl physics in crystalline materials and should stimulate further work on other potential materials, such as higher-order topological nodal-line semimetals.
Symmetry and topology are two fundamental aspects of many quantum states of matter. Recently new topological materials, higher-order topological insulators, were discovered, featuring ...bulk-edge-corner correspondence that goes beyond the conventional topological paradigms. Here we discover experimentally that the nonsymmorphic p4g acoustic metacrystals host a symmetry-protected hierarchy of topological multipoles: the lowest band gap has a quantized Wannier dipole and can mimic the quantum spin Hall effect, whereas the second band gap exhibits quadrupole topology with anomalous Wannier bands. Such a topological hierarchy allows us to observe experimentally distinct, multiplexed topological phenomena and to reveal a topological transition triggered by the geometry transition from the p4g group to the C
group, which demonstrates elegantly the fundamental interplay between symmetry and topology. Our study demonstrates that classical systems with controllable geometry can serve as powerful simulators for the discovery of novel topological states of matter and their phase transitions.
Prolonged exposure to negative stressors could be harmful if a subject cannot respond appropriately. Strategies evolved to respond to stress, including repetitive displacement behaviours, are ...important in maintaining behavioural homoeostasis. In rodents, self-grooming is a frequently observed repetitive behaviour believed to contribute to post-stress de-arousal with adaptive value. Here we identified a rat limbic di-synaptic circuit that regulates stress-induced self-grooming with positive affective valence. This circuit links hippocampal ventral subiculum to ventral lateral septum (LSv) and then lateral hypothalamus tuberal nucleus. Optogenetic activation of this circuit triggers delayed but robust excessive grooming with patterns closely resembling those evoked by emotional stress. Consistently, the neural activity of LSv reaches a peak before emotional stress-induced grooming while inhibition of this circuit significantly suppresses grooming triggered by emotional stress. Our results uncover a previously unknown limbic circuitry involved in regulating stress-induced self-grooming and pinpoint a critical role of LSv in this ethologically important behaviour.
Emerging studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in colorectal cancer (CRC). Here, we report a lncRNA, SATB2-AS1, which is specifically expressed in colorectal tissue ...and is significantly reduced in CRC. We systematically elucidated its functions and possible molecular mechanisms in CRC.
LncRNA expression in CRC was analyzed by RNA-sequencing and RNA microarrays. The expression level of SATB2-AS1 in tissues was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). The functional role of SATB2-AS1 in CRC was investigated by a series of in vivo and in vitro assays. RNA pull-down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), chromatin isolation by RNA purification (ChIRP), Bisulfite Sequencing PCR (BSP) and bioinformatics analysis were utilized to explore the potential mechanisms of SATB2-AS1.
SATB2-AS1 is specifically expressed in colorectal tissues and downregulated in CRC. Survival analysis indicates that decreased SATB2-AS1 expression is associated with poor survival. Functional experiments and bioinformatics analysis revealed that SATB2-AS1 inhibits CRC cell metastasis and regulates TH1-type chemokines expression and immune cell density in CRC. Mechanistically, SATB2-AS1 directly binds to WDR5 and GADD45A, cis-activating SATB2 (Special AT-rich binding protein 2) transcription via mediating histone H3 lysine 4 tri-methylation (H3K4me3) deposition and DNA demethylation of the promoter region of SATB2.
This study reveals the functions of SATB2-AS1 in CRC tumorigenesis and progression, suggesting new biomarkers and therapeutic targets in CRC.
Mounting evidence demonstrates that long noncoding RNAs (lncRNAs) have critical roles during the initiation and progression of cancers. In this study, we report that the small nucleolar RNA host gene ...1 (SNHG1) is involved in colorectal cancer progression.
We analyzed RNA sequencing data to explore abnormally expressed lncRNAs in colorectal cancer. The effects of SNHG1 on colorectal cancer were investigated through in vitro and in vivo assays (i.e., CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, xenograft model, immunohistochemistry, and western blot). The mechanism of SNHG1 action was explored through bioinformatics, RNA fluorescence in situ hybridization, luciferase reporter assay, RNA pull-down assay, chromatin immunoprecipitation assay and RNA immunoprecipitation assay.
Our analysis revealed that SNHG1 was upregulated in human colorectal cancer tissues, and high SNHG1 expression was associated with reduced patient survival. We also found that high SNHG1 expression was partly induced by SP1. Moreover, SNHG1 knockdown significantly repressed colorectal cancer cells growth both in vitro and in vivo. Mechanistic investigations demonstrated that SNHG1 could directly interact with Polycomb Repressive Complex 2 (PRC2) and modulate the histone methylation of promoter of Kruppel like factor 2 (KLF2) and Cyclin dependent kinase inhibitor 2B (CDKN2B) in the nucleus. In the cytoplasm, SNHG1 acted as a sponge for miR-154-5p, reducing its ability to repress Cyclin D2 (CCND2) expression.
Taken together, the results of our studies illuminate how SNHG1 formed a regulatory network to confer an oncogenic function in colorectal cancer and suggest that SNHG1 may serve as a potential target for colorectal cancer diagnosis and treatment.
16S rRNA sequencing of human fecal samples has been tremendously successful in identifying microbiome changes associated with both aging and disease. A number of studies have described microbial ...alterations corresponding to physical frailty and nursing home residence among aging individuals. A gut-muscle axis through which the microbiome influences skeletal muscle growth/function has been hypothesized. However, the microbiome has yet to be examined in sarcopenia. Here, we collected fecal samples of 60 healthy controls (CON) and 27 sarcopenic (Case)/possibly sarcopenic (preCase) individuals and analyzed the intestinal microbiota using 16S rRNA sequencing. We observed an overall reduction in microbial diversity in Case and preCase samples. The genera Lachnospira, Fusicantenibacter, Roseburia, Eubacterium, and Lachnoclostridium-known butyrate producers-were significantly less abundant in Case and preCase subjects while Lactobacillus was more abundant. Functional pathways underrepresented in Case subjects included numerous transporters and phenylalanine, tyrosine, and tryptophan biosynthesis suggesting that protein processing and nutrient transport may be impaired. In contrast, lipopolysaccharide biosynthesis was overrepresented in Case and PreCase subjects suggesting that sarcopenia is associated with a pro-inflammatory metagenome. These analyses demonstrate structural and functional alterations in the intestinal microbiota that may contribute to loss of skeletal muscle mass and function in sarcopenia.
In 2009, a mysterious illness associated with fever, thrombocytopenia, gastrointestinal symptoms, and leucopenia was seen in rural areas in central China, with an initial case fatality rate of 30%. ...After extensive investigation, a novel bunyavirus was identified.
Between late March and mid-July 2009, an emerging infectious disease, which was identified as the severe fever with thrombocytopenia syndrome (SFTS), was reported in rural areas of Hubei and Henan provinces in Central China. The cause of the illness was unknown. The major clinical symptoms included fever, thrombocytopenia, gastrointestinal symptoms, and leukocytopenia, and there was an unusually high initial case fatality rate of 30%. In June 2009, an investigation was performed to identify whether the disease was caused by
Anaplasma phagocytophilum
or other pathogens. Although the clinical symptoms were considered to resemble those of human anaplasmosis,
1
neither bacterial DNA nor . . .
Abnormal expression of long non-coding RNAs (lncRNAs) has been found in almost all human tumors, providing numerous potential diagnostic biomarkers, prognostic biomarkers, and therapeutic targets.
We ...analyzed RNA sequencing data to explore abnormally expressed lncRNAs in colorectal cancer (CRC). The functions of small nucleolar RNA host gene 6 (SNHG6) were investigated through in vitro and in vivo assays (CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, wound healing assay, transwell assay, and xenograft model). The mechanism of action of SNHG6 was explored through bioinformatics, RNA fluorescence in situ hybridization, luciferase reporter assay, RNA pull-down assay, chromatin immunoprecipitation assay, and RNA immunoprecipitation assay.
We identified aberrantly expressed lncRNAs in CRC. We found that elevated SNHG6 expression was associated with poor prognosis and CRC progression. We also demonstrated that the high SNHG6 expression was partly due to DNA copy number gains and SP1 induction. Functional studies showed that SNHG6 promoted CRC cell growth, migration, and invasion both in vitro and in vivo. Mechanistically, we found that SNHG6 expressed predominantly in the cytoplasm. SNHG6 could interact with miR-26a, miR-26b, and miR-214 and regulate their common target EZH2.
Our study elucidated that SNHG6 acted as an oncogene in CRC, which might serve as a novel target for CRC diagnosis and therapy.
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