Discovery of Higher-Order Nodal Surface Semimetals.

The emergent higher-order topological insulators significantly deepen our understanding of topological physics. Recently, the study has been extended to topological semimetals featuring gapless bulk band nodes. To date, higher-order nodal point and line semimetals have been successfully realized in different physical platforms. However, for the conceptually expected higher-order nodal surface semimetals, a concrete model has yet to be proposed, let alone experimentally observed. Here, we report an ingenious design route for constructing this unprecedented higher-order topological phase. The three-dimensional model, layer-stacked with a two-dimensional anisotropic Su-Schrieffer-Heeger lattice, exhibits appealing hinge arcs connecting the projected nodal surfaces. Experimentally, we realize this new topological phase in an acoustic metamaterial, and present unambiguous evidence for both the bulk nodal structure and hinge arc states, the two key manifestations of the higher-order nodal surface semimetal. Our findings can be extended to other classical systems such as photonic, elastic, and electric circuit systems, and open new possibilities for controlling waves.

Construction and Observation of Flexibly Controllable High-Dimensional Non-Hermitian Skin Effects.

Non-Hermitian skin effect (NHSE) is one of the most fundamental phenomena in non-Hermitian physics. It is established that 1D NHSE originates from the nontrivial spectral winding topology. However, the topological origin behind the higher-dimensional NHSE remains unclear, which poses a substantial challenge in constructing and manipulating high-dimensional NHSEs. Here, an intuitive bottom-to-top scheme to construct high-dimensional NHSEs is proposed, through assembling multiple independent 1D NHSEs. Not only the elusive high-dimensional NHSEs can be effectively predicted from the well-defined 1D spectral winding topologies, but also the high-dimensional generalized Brillouin zones can be directly synthesized from the 1D counterparts. As examples, two 2D nonreciprocal acoustic metamaterials are experimentally implemented to demonstrate highly controllable multi-polar NHSEs and hybrid skin-topological effects, where the sound fields can be frequency-selectively localized at any desired corners and boundaries. These results offer a practicable strategy for engineering high-dimensional NHSEs, which can boost advanced applications such as selective filters and directional amplifiers.

High LGALS3 expression induced by HCP5/hsa-miR-27b-3p correlates with poor prognosis and tumor immune infiltration in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is widely recognized for its unfavorable prognosis. Increasing evidence has revealed that LGALS3 has an essential function in initiating and developing several malignancies in humans. Nevertheless, thorough analysis of the expression profile, clinical prognosis, pathway prediction, and immune infiltration of LGALS3 has not been fully explored in HCC. METHODS: In this study, an initial pan-cancer analysis was conducted to investigate the expression and prognosis of LGALS3. Following a comprehensive analysis, which included expression analysis and correlation analysis, noncoding RNAs that contribute to the overexpression of LGALS3 were subsequently identified. This identification was further validated using HCC clinical tissue samples. TIMER2 and GEPIA2 were employed to examine the correlation between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration in HCC. The R program was applied to analyze the expression distribution of immune score in in HCC patients with high and low LGALS3 expression. The expression profiles of immune checkpoints were also analyzed. Use R to perform GSVA analysis in order to explore potential signaling pathways. RESULTS: First, we conducted pan-cancer analysis for LGALS3 expression level through an in-depth analysis of public databases and found that HCC has a high LGALS3 gene and protein expression level, which were then verified in clinical HCC specimens. Meanwhile, high LGALS3 gene expression is related to malignant progression and poor prognosis of HCC. Univariate and multivariate analyses confirmed that LGALS3 could serve as an independent prognostic marker for HCC. Next, by combining comprehensive analysis and validation on HCC clinical tissue samples, we hypothesize that the HCP5/hsa-miR-27b-3p axis could serve as the most promising LGALS3 regulation mechanism in HCC. KEGG and GO analyses highlighted that the LGALS3-related genes were involved in tumor immunity. Furthermore, we detected a significant positive association between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration. In addition, high LGALS3 expression groups had significantly higher immune cell scores and immune checkpoint expression levels. Finally, GSVA analysis was performed to predict potential signaling pathways linked to LGALS3 and HCP5 in immune evasion and metabolic reprogramming of HCC. CONCLUSIONS: Our findings indicated that the upregulation of LGALS3 via the HCP5/hsa-miR-27b-3p axis is associated with unfavorable prognosis and increased tumor immune infiltration in HCC.

Stiffness promotes cell migration, invasion, and invadopodia in nasopharyngeal carcinoma by regulating the WT-CTTN level.

Matrix stiffness potently promotes the malignant phenotype in various biological contexts. Therefore, identification of gene expression to participate in mechanical force signals transduced into downstream biochemical signaling will contribute substantially to the advances in nasopharyngeal carcinoma (NPC) treatment. In the present study, we detected that cortactin (CTTN) played an indispensable role in matrix stiffness-induced cell migration, invasion, and invadopodia formation. Advances in cancer research have highlighted that dysregulated alternative splicing contributes to cancer progression as an oncogenic driver. However, whether WT-CTTN or splice variants (SV1-CTTN or SV2-CTTN) regulate matrix stiffness-induced malignant phenotype is largely unknown. We proved that alteration of WT-CTTN expression modulated matrix stiffness-induced cell migration, invasion, and invadopodia formation. Considering that splicing factors might drive cancer progression through positive feedback loops, we analyzed and showed how the splicing factor PTBP2 and TIA1 modulated the production of WT-CTTN. Moreover, we determined that high stiffness activated PTBP2 expression. Taken together, our findings showed that the PTBP2-WT-CTTN level increases upon stiffening and then promotes cell migration, invasion, and invadopodia formation in NPC.

FGF19 promotes nasopharyngeal carcinoma progression by inducing angiogenesis via inhibiting TRIM21-mediated ANXA2 ubiquitination.

PURPOSE: Nasopharyngeal carcinoma (NPC) has characteristics of high invasion and early metastasis. Most NPC patients present with locoregionally advanced illness when first diagnosed. Therefore, it is urgent to discover NPC biomarkers. Fibroblast growth Factor 19 (FGF19) plays a role in various physiological or pathological processes, including cancer. In this research, we discovered the importance of FGF19 in NPC, and clarified its role in tumour angiogenesis. METHODS: Western blotting, immunohistochemistry and ELISA were used to investigate FGF19 expression in NPC. Then we took CCK8, colony formation, Transwell and wound healing assays to identify the influence of FGF19 on NPC malignant behaviours. The proliferative and metastatic capacity of FGF19 were evaluated in nude mice and zebrafish. The role of FGF19 in angiogenesis was investigated by tube formation and Matrigel plug angiogenesis assays. We then evaluated the variation in Annexin A2(ANXA2) levels with the treatment of FGF19. Lastly, co-immunoprecipitation and ubiquitination assays were performed to identify the mechanisms involved. RESULTS: FGF19 levels were elevated in tissues and serum of NPC patients and were associated with poor clinical stages. High expression of FGF19 promoted NPC malignant behaviours. In particular, FGF19 expression was correlated with microvessel density in tissues and NPC-derived FGF19 could accelerate angiogenesis in vitro and in vivo. Mechanistically, FGF19 influenced ANXA2 expression to promote angiogenesis. Moreover, tripartite motif-containing 21(TRIM21) interacted with ANXA2 and was responsible for ANXA2 ubiquitination. CONCLUSION: FGF19 promoted NPC angiogenesis by inhibiting TRIM21-mediated ANXA2 ubiquitination. It may serve as a noninvasive biomarker for NPC and provides new insights for therapy.

N-Terminalized Ti3 C2 Tx MXene for Supercapacitor with Extraordinary Pseudocapacitance Performance.

MXenes have demonstrated significant potential in electrochemical energy storage, particularly in supercapacitors, owing to their exceptional properties. The surface terminal groups of MXene play a pivotal role in pseudocapacitive mechanism. Considering the hindered electrolyte ion transport caused by -F terminal groups and the limited ion binding sites associated with -O terminal groups, this study proposes a novel strategy of replacing -F with -N terminal groups. The modulated MXene-N electrode, featuring a substantial number of -N terminal groups, demonstrates an exceptionally high gravimetric capacitance of 566 F g-1 (at a scan rate of 2 mV s-1 ) or 588 F g-1 (at a discharge rate of 1 A g-1 ) in 1 м H2 SO4 electrolyte, and the potential window is significantly increased. Furthermore, subsequent spectra analysis and density functional theory calculations are employed to investigate the mechanism associated with -N terminal groups. This work exemplifies the significance of terminal modulation in the context of electrochemical energy storage.

Phenethyl isothiocyanate inhibits metastasis potential of non-small cell lung cancer cells through FTO mediated TLE1 m6A modification.

N6-methyladenosine (m6A) modification is a prevalent RNA epigenetic modification, which plays a crucial role in tumor progression including metastasis. Isothiocyanates (ITCs) are natural compounds and inhibit the tumorigenesis of various cancers. Our previous studies show that ITCs inhibit the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells, and have synergistic effects with chemotherapy drugs. In this study, we investigated the molecular mechanisms underlying the inhibitory effects of ITCs on cancer cell metastasis. We showed that phenethyl isothiocyanate (PEITC) dose-dependently inhibited the cell viability of both NSCLC cell lines H1299 and H226 with IC50 values of 17.6 and 15.2 µM, respectively. Furthermore, PEITC dose-dependently inhibited the invasion and migration of H1299 and H226 cells. We demonstrated that PEITC treatment dose-dependently increased m6A methylation levels and inhibited the expression of the m6A demethylase fat mass and obesity-associated protein (FTO) in H1299 and H226 cells. Knockdown of FTO significantly increased m6A methylation in H1299 and H226 cells, impaired their abilities of invasion and migration in vitro, and enhanced the inhibition of PEITC on tumor growth in vivo. Overexpression of FTO promoted the migration of NSCLC cells, and also mitigated the inhibitory effect of PEITC on migration of NSCLC cells. Furthermore, we found that FTO regulated the mRNA m6A modification of a transcriptional co-repressor Transducin-Like Enhancer of split-1 (TLE1) and further affected its stability and expression. TCGA database analysis revealed TLE1 was upregulated in NSCLC tissues compared to normal tissues, which might be correlated with the metastasis status. Moreover, we showed that PEITC suppressed the migration of NSCLC cells by inhibiting TLE1 expression and downstream Akt/NF-κB pathway. This study reveals a novel mechanism underlying ITC's inhibitory effect on metastasis of lung cancer cells, and provided valuable information for developing new therapeutics for lung cancer by targeting m6A methylation.

Effects of adding steel slag on humification and characteristics of bacterial community during phosphate-amended composting of municipal sludge.

This study aimed to investigate the effects of different proportions (0%, 5%, 7.5%, and 10%) of steel slag (SS) on humification and bacterial community characteristics during phosphate-amended composting of municipal sludge. Compared with adding KH2PO4 alone, co-adding SS significantly promoted the temperature, pH, nitrification, and critical enzyme activities (polyphenol oxidase, cellulase, laccase); especially organic matter (OM) degradation rate (25.5%) and humification degree (1.8) were highest in the 5%-SS treatment. Excitation-emission matrix-parallel factor confirmed that co-adding SS could promote the conversion of protein-like substances or microbial by-products into humic-like substances. Furthermore, adding 5%-SS significantly improved the relative abundances of Actinobacteria, Firmicutes and the genes related to carbohydrate and amino acid metabolism, and enhanced the interactions of bacterial community in stability and complexity. The partial least squares path model indicated that OM was the primary factor affecting humification. These results provided a promising strategy to optimize composting of municipal sludge via SS.

Experimental Investigation of Wave Propagation Characteristics in Entangled Metallic Wire Materials by Acoustic Emission.

In this paper, the response characteristics of wave propagation in entangled metallic wire materials (EMWMs) are investigated by acoustic emission. The frequency, amplitude of wave emission, and the pre-compression force of the specimen can be adjusted in the experimental setup. EMWM specimens fabricated from stainless steel wires and with different design parameters are tested in this work. The results show that waves of different amplitudes propagate in EMWMs with approximate linear characteristics and the fluctuation coefficient of wave passing ratios is calculated below 15%. The response spectrum of passing waves shows a distinct single-peak characteristic, with the peak response at approximately 14 kHz. The parameters of pre-compression force, porosity, wire diameter, helix diameter, specimen height, and the layered structure of specimens have no significant effect on the frequency characteristics but moderately affect the wave passing ratios. Notably, EMWMs exhibit a lower wave passing ratio (ranging from 0.01 to 0.18) compared to aluminum alloy and natural rubber. The characteristics of response spectrums can be successfully reproduced by the finite element simulation. This work demonstrates EMWMs' potential as an acoustic frequency vibration isolation material, offering excellent performance and engineering design convenience.

The role of regulators of RNA m6A methylation in lung cancer.

N6-methyladenosine (m6A) modification is found the most prevalent and abundant post-transcriptional mRNA modification in eukaryotic cells. It regulates almost all stages of RNA life cycle including splicing, translocation, stability, decay and translation. As a dynamic and reversible process, m6A modification is catalyzed by the RNA methyltransferases ('writers'), removed by the demethylases ('erasers'), and interacts with m6A-binding proteins ('readers'). Recent studies have revealed that these m6A modification regulators are frequently expressed aberrantly in various types of cancer, and involved in cell proliferation, differentiation, metabolism, particularly, in tumorigenesis and tumor progression through diverse mechanisms. In this review, the m6A modification process and its regulatory functions in lung cancer are summarized. Furthermore, the research progress in the inhibitor development of m6A modification, and the potential of targeting m6A modifying proteins for clinical application are discussed.

Cancer-associated fibroblasts promote migration and invasion of non-small cell lung cancer cells via METTL3-mediated RAC3 m6A modification.

Cancer progression depends on the communication between tumor cells and tumor microenvironment. Cancer-associated fibroblasts (CAFs) are a major component of stromal cells. CAFs promote cancer metastasis; however, it has not been evaluated whether N6-methyladenosine (m6A) modification is responsible for CAFs' role in metastasis. In the present study, we found that CAFs promoted migration and invasion of non-small cell lung cancer (NSCLC) cells by elevating m6A modification in NSCLC cells. Methyltransferase-like 3 (METTL3) in NSCLC cells mediated CAFs' effect on m6A modification, and was regulated by CAFs-secreted vascular endothelial growth factor A (VEGFA). METTL3 knockdown in NSCLC cells dramatically inhibited cell migration and invasion, and suppressed tumor growth in vivo. Database analysis revealed that METTL3 was associated with poor prognosis of lung cancer. The mechanism study showed that METTL3 increased m6A level of RAC3 mRNA, resulting in increased stability and translation of RAC3 mRNA. RAC3 was responsible for the CAFs' promoting effect on cell migration via the AKT/NF-κB pathway. This study established a CAF-METTL3-RAC3 m6A modification-dependent regulation system in NSCLC metastasis, suggesting potential candidates for metastasis treatment.

Minimal non-abelian nodal braiding in ideal metamaterials.

Exploring new topological phases and phenomena has become a vital topic in condensed matter physics and materials sciences. Recent studies reveal that a braided colliding nodal pair can be stabilized in a multi-gap system with [Formula: see text] or [Formula: see text] symmetry. This exemplifies non-abelian topological charges beyond the scope of conventional single-gap abelian band topology. Here, we construct ideal acoustic metamaterials to realize non-abelian braiding with the fewest band nodes. By emulating the time with a sequence of acoustic samples, we experimentally observe an elegant but nontrivial nodal braiding process, including nodes creation, braiding, collision, and repulsion (i.e., impossible to annihilate), and measure the mirror eigenvalues to elucidate the braiding consequence. The latter, at the level of wavefunctions, is of prime importance since essentially braiding physics aims to entangle multi-band wavefunctions. Furthermore, we experimentally unveil the highly intricate correlation between the multi-gap edge responses and the bulk non-abelian charges. Our findings pave the way for developing non-abelian topological physics that is still in its infancy.

Universal Mirror-Stacking Approach for Constructing Topological Bound States in the Continuum.

Bound states in the continuum (BICs) are counterintuitive localized states with eigenvalues embedded in the continuum of extended states. Recently, nontrivial band topology is exploited to enrich the BIC physics, resulting in topological BICs (TBICs) with extraordinary robustness against perturbations or disorders. Here, we propose a simple but universal mirror-stacking approach to turn nontrivial bound states of any topological monolayer model into TBICs. Physically, the mirror-stacked bilayer Hamiltonian can be decoupled into two independent subspaces of opposite mirror parities, each of which directly inherits the energy spectrum information and band topology of the original monolayer. By tuning the interlayer couplings, the topological bound state of one subspace can move into and out of the continuum of the other subspace continuously without hybridization. As representative examples, we construct one-dimensional first-order and two-dimensional higher-order TBICs, and demonstrate them unambiguously by acoustic experiments. Our findings will expand the research implications of both topological materials and BICs.

Hypoxic nasopharyngeal carcinoma-derived exosomal miR-455 increases vascular permeability by targeting ZO-1 to promote metastasis.

Nasopharyngeal carcinoma (NPC), the most frequent reason for treatment failure in head and neck tumors, has the greatest incidence of distant metastases. Increased vascular permeability facilitates metastasis. Exosomal microRNAs (miRNAs) have been implicated in the development of the premetastatic niche and are emerging as prospective biomarkers in cancer patients. We discovered that a higher level of miR-455 was connected to a larger propensity for NPC metastasis based on deep sequencing and RT-qPCR. We found that hypoxia promoted NPC exosomes release and increased miR-455 expression in a way that was hypoxia-inducible factor 1-alpha (HIF-1α) dependent. Exosomes from NPC cells with high levels of miR-455 were found to specifically target zonula occludens 1 (ZO-1), increasing the permeability of endothelial monolayers in vitro vascular permeability and transendothelial invasion experiments. Additional in vivo studies showed that zebrafish with sustained miR-455-overexpressing NPC cell xenografts displayed increased tumor cell mass throughout the body. In vivo, zebrafish vascular tight junction integrity was disrupted by exosomes produced by NPC cells with elevated miR-455 expression. Mice-bearing xenografts further supported the finding that exosomes containing miR-455 might reduce ZO-1 expression in addition to promote NPC cell growth. These findings suggest that in a hypoxic microenvironment, exosomal miR-455 released by NPC cells enhances vascular permeability and promotes metastasis by targeting ZO-1. The HIF-1α-miR-455-ZO-1 signaling pathway may be a promising predictor and potential therapeutic target for NPC with metastasis.

General duality and magnet-free passive phononic Chern insulators.

Integrated phononics plays an important role in both fundamental physics and technology. Despite great efforts, it remains a challenge to break time-reversal symmetry to achieve topological phases and non-reciprocal devices. Piezomagnetic materials offer an intriguing opportunity as they break time-reversal symmetry intrinsically, without the need for an external magnetic field or an active driving field. Moreover, they are antiferromagnetic, and possibly compatible with superconducting components. Here, we develop a theoretical framework that combines linear elasticity with Maxwell's equations via piezoelectricity and/or piezomagnetism beyond the commonly adopted quasi-static approximation. Our theory predicts and numerically demonstrates phononic Chern insulators based on piezomagnetism. We further show that the topological phase and chiral edge states in this system can be controlled by the charge doping. Our results exploit a general duality relation between piezoelectric and piezomagnetic systems, which can potentially be generalized to other composite metamaterial systems.

Observation of Acoustic Non-Hermitian Bloch Braids and Associated Topological Phase Transitions.

Topological features embedded in ancient braiding and knotting arts endow significant impacts on our daily life and even cutting-edge science. Recently, fast growing efforts are invested to the braiding topology of complex Bloch bands in non-Hermitian systems. This new classification of band topology goes far beyond those established in Hermitian counterparts. Here, we present the first acoustic realization of the topological non-Hermitian Bloch braids, based on a two-band model easily accessible for realizing any desired knot structure. The non-Hermitian bands are synthesized by a simple binary cavity-tube system, where the long-range, complex-valued, and momentum-resolved couplings are accomplished by a well-controlled unidirectional coupler. In addition to directly visualizing various two-band braiding patterns, we unambiguously observe the highly elusive topological phase transitions between them. Not only do our results provide a direct demonstration for the non-Hermitian band topology, but also the experimental techniques open new avenues for designing unconventional acoustic metamaterials.

Cancer-associated fibroblasts in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) has a relatively good prognosis, yet there are some invasive PTC cases with worse clinicopathological features and poor outcome. Cancer-associated fibroblasts (CAFs) play an important role in cancer invasion and metastasis. This study aimed to investigate the expression of marker proteins of CAFs in PTC and their correlations with clinicopathological features through immunohistochemistry. The medical records of 125 PTC patients were reviewed in this study, whose specimens were retrieved for immunohistochemistry. Four CAFs marker proteins, FAP fibroblast activated protein (FAP), α-smooth muscle actin (α-SMA), Vimentin and platelet-derived growth factor receptor-α(PDGFR-α), were stained and scored. Then, statistical analyses were performed. The immunoreactivity scores of FAP and α-SMA correlated with tumor size, BRAF mutation, extrathyroidal, invasion, pathological subtype, lymph node metastasis and ATA risk stratification. Moreover, binary logistic regression analysis and receiver operating characteristic curves showed that high FAP and α-SMA immunoreactivity scores were risk factors for extrathyroidal invasion, BRAF mutation, multi-focality and lymph node metastasis (especially N1b) with good sensitivity and accuracy in prediction. A better performance was found in FAP than α-SMA. Strong expressions of CAFs were risk factors for worse thyroid cancer clinicopathological features. FAP was the better CAFs marker for PTC.

Coupled Co-Doped MoS2 and CoS2 as the Dual-Active Site Catalyst for Chemoselective Hydrogenation.

Catalytic hydrogenation plays an important role in the industrial production of fine chemicals. Herein, we report a Co-doped MoS2 and CoS2 composite with a coupling interface and successfully apply it for the chemoselective hydrogenation of p-chloronitrobenzene to p-chloroaniline. The target catalyst 0.5CoMoS has ∼100% conversion and ∼100% selectivity. Experiments and theoretical calculations reveal that CoS2 is more favorable for adsorbing and activating H2 and provides active hydrogen (Ha) to Co-doped MoS2 by the coupling interface. By matching the production and consumption rates of Ha, the maximization of the reaction yield was achieved. This work may promote the study of MoS2-based catalysts for chemoselective hydrogenation.

Brain-targeted antigen-generating nanoparticles improve glioblastoma prognosis.

The exploration of multifunctional nanomedicine has prompted interest in improving glioblastoma (GBM) prognosis. In this study, we constructed tumor microenvironment (TME)-responsive magnetic therapeutic nanoparticles (BK@MTNPs) as a multifunctional drug delivery platform. It contains the following components. [Des-arg(Sheets et al., 2020 [9])]bradykinin (BK), which contributes to the transient opening of the blood-brain barrier (BBB) and targeting of GBM cells; nanoparticles (NPs) encapsulated in MTNPs, which act as an in vivo magnetic resonance (MR) imaging agent; crizotinib, which is an inhibitor of protein kinase c-Met; and the immune drug anti-PDL1 antibody. These components were loaded into BK@MTNPs for complete tumoricidal effects. Abundant glutathione in the TME can promote BK@MTNP degradation by interrupting the disulfide bonds between cysteine residues. Such BK@MTNPs support a synergistic tumoricidal effect by inducing DNA damage, activating the transcription of the tumor suppressor gene PTEN, inhibiting glioblastoma stem cell function, activating cytotoxic T lymphocytes, and reprogramming tumor-associated macrophages. BK@MTNPs showed a significant increase in antitumor activity compared with free drugs in vitro. Furthermore, in mice bearing orthotopic GBM, treatment with BK@MTNPs resulted in marked tumor inhibition and greatly extended survival time with minimal side effects. This study demonstrates the advantages of chemo-immunotherapeutic NPs accumulated in the GBM area and their effective inhibition of GBM growth, thus establishing a delivery platform to promote antitumor immunity against GBM.

Rapid microwave-assisted synthesis of Ni2P nanosheets from black phosphorus.

The high dielectric loss tangent value of black phosphorus nanosheets enables them to be selectively heated under microwave radiation to realize the in situ surface reaction of BP with Ni2+ to prepare thermodynamically unstable two-dimensional Ni2P.