The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis.

To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.

Acoustic Metagrating Holograms.

Metasurface holograms represent a common category of metasurface devices that utilize in-plane phase gradients to shape wavefronts, forming holographic images through the application of the generalized Snell's law (GSL). While conventional metasurfaces focus solely on phase gradients, metagratings, which incorporate higher-order wave diffraction, further expand the GSL's generality. Recent advances in certain acoustic metagratings demonstrate an updated GSL extension capable of reversing anomalous transmission and reflection, whose reversal is characterized by the parity of the number of wave propagation trips through the metagrating. However, the current extension of GSL remains limited to 1D metagratings, unable to access 2D holographic images in 3D spaces. Here, the GSL extension to 2D metagratings for manipulating waves within 3D spaces is investigated. Through this analysis, a series of acoustic metagrating holograms is experimentally demonstrated. These holographic images exhibit the unique ability to switch between transmission and reflection types independently. This study introduces an additional dimension to modern holography design and metasurface wavefront manipulation.

Observation of vortex-string chiral modes in metamaterials.

As hypothetical topological defects in the geometry of spacetime, vortex strings could have played many roles in cosmology, and their distinct features can provide observable clues about the early universe's evolution. A key feature of vortex strings is that they can interact with Weyl fermionic modes and support massless chiral-anomaly states along strings. To date, despite many attempts to detect vortex strings in astrophysics or to emulate them in artificially created systems, observation of these vortex-string chiral modes remains experimentally elusive. Here we report experimental observations of vortex-string chiral modes using a metamaterial system. This is implemented by inhomogeneous perturbation of Yang-monopole phononic metamaterials. The measured linear dispersion and modal profiles confirm the existence of topological modes bound to and propagating along the string with the chiral anomaly. Our work provides a platform for studying diverse cosmic topological defects in astrophysics and offers applications as topological fibres in communication techniques.

Three-dimensional flat Landau levels in an inhomogeneous acoustic crystal.

When electrons moving in two dimensions (2D) are subjected to a strong uniform magnetic field, they form flat bands called Landau levels (LLs). LLs can also arise from pseudomagnetic fields (PMFs) induced by lattice distortions. In three-dimensional (3D) systems, there has been no experimental demonstration of LLs  as a type of flat band thus far. Here, we report the experimental realization of a flat 3D LL in an acoustic crystal. Starting from a lattice whose bandstructure exhibits a nodal ring, we design an inhomogeneous distortion corresponding to a specific pseudomagnetic vector potential (PVP). This distortion causes the nodal ring states to break up into LLs, including a zeroth LL that is flat along all three directions. These findings suggest the possibility of using nodal ring materials to generate 3D flat bands, allowing access to strong interactions and other attractive physical regimes in 3D.

[Corrigendum] Fully human VEGFR2 monoclonal antibody BC001 attenuates tumor angiogenesis and inhibits tumor growth.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, for the scratch wound assay experiments shown in Fig. 1 on p. 2413, the panels showing the '0 h' experiments for the respective incubations with VEGF or BC001 were apparently identical. The authors were able to re­examine their original data files, and realized that this figure had been inadverently assembled incorrectly. The revised version of Fig. 1, containing the correct data for the '0 h / BC001' panel, is shown below. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [International Journal of Oncology 45: 2411­2420, 2014; DOI: 10.3892/ijo.2014.2690].

[Spatial Distribution, Speciation, and Ecological Risk Assessment of Heavy Metals in Surface Sediments of Dongjiang Lake, Hunan Province].

To understand the heavy metal pollution status of Dongjiang Lake, the contents and species of heavy metals in the surface sediments were investigated during September 2021, and the heavy metal pollution level and potential ecological risk were evaluated. The results showed that Cd, Pb, As, Cu, Zn, Ni, and Cr contents were in the range of 0.40-34.1, 14.8-1688, 6.99-1155, 6.89-280, 26.2-1739, 6.29-55.4, and 23.3-44.8 mg·kg-1, respectively, with extremely uneven spatial distributions. The highest contents of Cd, Pb, As, Zn, Cu, and Ni were found in the site adjacent to Yaogangxian tungsten ore. The proportion of metal species with bioavailability was high, in which Cd in acid-soluble species was 46.7%-71.5% and Pb in reducible species was 46.8%-67.0%. The bioavailable species of Cu, Zn, Ni, and Cr were 35%-68%, 42%-72%, 26%-51%, and 6%-30%, respectively, although they primarily existed in residual species. According to the geo-accumulation index (Igeo), there was a moderate or extreme pollution status of Cd in all sites, moderate or extreme pollution status of Pb in 90% of sites, and moderate pollution status of As, Cu, and Zn in 30% of sites. The ecological risk factor (Eri) of Cd showed high potential ecological risk in all sites with significantly high potential ecological risk in 80% of sites. Moreover, As and Pb had significantly high potential ecological risk, and Cu had moderate potential ecological risk in S7, which was adjacent to Yaogangxian tungsten ore. There was a high total potential ecological risk in all sites and significantly high potential ecological risk in 50% of sites. Therefore, the surface sediments of Dongjiang Lake were under the combined pollution of Cd, Pb, As, Zn, and Cu with high bioavailability and high total potential ecological risk.

Dihydroergotamine ameliorates liver fibrosis by targeting transforming growth factor ß type II receptor.

BACKGROUND: The transforming growth factor ß (TGFß) signaling pathway plays a crucial role in the development of liver fibrosis by activating TGFß type II receptor (TGFßR2), followed by the recruitment of TGFßR1 finally triggering downstream signaling pathway. AIM: To find drugs targeting TGFßR2 that inhibit TGFßR1/TGFßR2 complex formation, theoretically inhibit TGFß signaling pathway, and thereby ameliorate liver fibrosis. METHODS: Food and Drug Administration-approved drugs were screened for binding affinity with TGFßR2 by virtual molecular docking. We identified 6 candidates and further explored their potential by Cell Counting Kit-8 (CCK-8) cell cytotoxic experiment to validate toxicity and titrated the best cellular working concentrations. Next, we further demonstrated the detailed molecular working mechanisms using mutagenesis analysis. Finally, we used a mouse model to investigate its potential anti-liver fibrosis effect. RESULTS: We identified 6 drug candidates. Among these 6 drugs, dihydroergotamine (DHE) shows great ability in reducing fibrotic gene expressions such as collagen, p-SMAD3, and α-SMA in TGFß induced cellular model of liver fibrosis in LX-2 cells. Furthermore, we demonstrated that DHE binds to TGFßR2. Moreover, mutation of Leu27, Phe30, Thr51, Ser52, Ile53, and Glu55 of TGFßR2 disrupted the binding of TGFßR2 with DHE. In addition, DHE significantly improved liver fibrosis, as evidenced by Masson's trichrome staining of liver sections. This is further supported by the width and the velocity of the portal vein, and serum markers of liver function. In line with those observations, DHE also decreased macrophages infiltration and extracellular matrix deposition in the liver. CONCLUSION: DHE alleviates liver fibrosis by binding to TGFßR2 thereby suppressing TGFß signaling pathway. We show here that as far as drug repurposing, DHE has great potential to treat liver fibrosis.

Manipulation of Organic Afterglow in Fluoranthene-Containing Dopant-Matrix Systems: From Conventional Room-Temperature Phosphorescence to Efficient Red TADF-Type Organic Afterglow.

It remains challenging to fabricate highly-efficient and long-lived organic afterglow materials, especially in the case of red afterglow systems. Here we develop advanced charge transfer (CT) technology to boost afterglow efficiency and lifetimes in fluoranthene-containing dopant-matrix systems. First, organic CT molecules possess singlet-triplet splitting energy (ΔEST ) of around 0.5 eV, much smaller than localized excitation systems. Second, upon doping into suitable organic matrices, dipole-dipole interactions between 1 CT states and organic matrices reduce 1 CT levels with less effect on 3 CT levels, and thus further narrow ΔEST and enhance intersystem crossing. Third, the rigid planar structure of fluoranthene groups and the rigid microenvironment provided by organic matrices can suppress phosphorescence quenching. Forth, the multiple donor design enables spectral red-shifts to red region and switches on TADF mechanism to improve afterglow efficiency to 13.1 % and maintain afterglow lifetime of 0.1 s. Such high-performance afterglow materials have been rarely explored in reported studies.

Spinful Topological Phases in Acoustic Crystals with Projective PT Symmetry.

For the classification of topological phases of matter, an important consideration is whether a system is spinless or spinful, as these two classes have distinct symmetry algebra that gives rise to fundamentally different topological phases. However, only recently has it been realized theoretically that in the presence of gauge symmetry, the algebraic structure of symmetries can be projectively represented, which possibly enables the switch between spinless and spinful topological phases. Here, we report the experimental demonstration of this idea by realizing spinful topological phases in "spinless" acoustic crystals with projective space-time inversion symmetry. In particular, we realize a one-dimensional topologically gapped phase characterized by a 2Z winding number, which features double-degenerate bands in the entire Brillouin zone and two pairs of degenerate topological boundary modes. Our Letter thus overcomes a fundamental constraint on topological phases by spin classes.

Observation of Dirac Hierarchy in Three-Dimensional Acoustic Topological Insulators.

Dirac cones (DCs) play a pivotal role in various unique phenomena ranging from massless electrons in graphene to robust surface states in topological insulators (TIs). Recent studies have theoretically revealed a full Dirac hierarchy comprising an eightfold bulk DC, a fourfold surface DC, and a twofold hinge DC, associated with a hierarchy of topological phases including first-order to third-order three-dimensional (3D) topological insulators, using the same 3D base lattice. Here, we report the first experimental observation of the Dirac hierarchy in 3D acoustic TIs. Using acoustic measurements, we unambiguously reveal that lifting of multifold DCs in each hierarchy can induce two-dimensional topological surface states with a fourfold DC in a first-order 3D TI, one-dimensional topological hinge states with a twofold DC in a second-order 3D TI, and zero-dimensional topological corner states in a third-order 3D TI. Our Letter not only expands the fundamental research scope of Dirac physics, but also opens up a new route for multidimensional robust wave manipulation.

Differences of core genes in liver fibrosis and hepatocellular carcinoma: Evidence from integrated bioinformatics and immunohistochemical analysis.

BACKGROUND: Liver fibrosis and hepatocellular carcinoma (HCC) are common adverse consequences of chronic liver injury. The interaction of various risk factors may cause them to happen. Identification of specific biomarkers is of great significance for understanding the occurrence, development mechanisms, and determining the novel tools for diagnosis and treatment of both liver fibrosis and HCC. AIM: To identify liver fibrosis-related core genes, we analyzed the differential expression pattern of core genes in liver fibrosis and HCC. METHODS: Gene expression profiles of three datasets, GSE14323, GSE36411, and GSE89377, obtained from the Gene Expression Omnibus (GEO) database, were analyzed, and differentially expressed genes (DEGs) between patients with liver cirrhosis and healthy controls were identified by screening via R software packages and online tool for Venn diagrams. The WebGestalt online tool was used to identify DEGs enriched in biological processes, molecular functions, cellular components, and Kyoto Encyclopedia of Genes and Genomes pathways. The protein-protein interactions of DEGs were visualized using Cytoscape with STRING. Next, the expression pattern of core genes was analyzed using Western blot and immunohistochemistry in a carbon tetrachloride (CCl4)-induced liver cirrhosis mouse model and in patient liver samples. Finally, Kaplan-Meier curves were constructed using the Kaplan-Meier plotter online server. RESULTS: Forty-five DEGs (43 upregulated and 2 downregulated genes) associated with liver cirrhosis were identified from three GEO datasets. Ten hub genes were identified, which were upregulated in liver cirrhosis. Western blot and immunohistochemical analyses of the three core genes, decorin (DCN), dermatopontin (DPT), and SRY-box transcription factor 9 (SOX9), revealed that they were highly expressed in the CCl4-induced liver cirrhosis mouse model. The expression levels of DCN and SOX 9 were positively correlated with the degree of fibrosis, and SOX 9 level in HCC patients was significantly higher than that in fibrosis patients. However, high expression of DPT was observed only in patients with liver fibrosis, and its expression in HCC was low. The gene expression profiling interactive analysis server (GEPIA) showed that SOX9 was significantly upregulated whereas DCN and DPT were significantly downregulated in patients with HCC. In addition, the Kaplan-Meier curves showed that HCC patients with higher SOX9 expression had significantly lower 5-year survival rate, while patients with higher expression of DCN or DPT had significantly higher 5-year survival rates. CONCLUSION: The expression levels of DCN, DPT, and SOX9 were positively correlated with the degree of liver fibrosis but showed different correlations with the 5-year survival rates of HCC patients.

Manipulation of Triplet Excited States in Two-Component Systems for High-Performance Organic Afterglow Materials.

The past several years have witnessed the tremendous development of novel chemical structures, new design strategies and intriguing applications in the field of room-temperature phosphorescence (RTP) and organic afterglow materials. This Review article focuses on recent advancements of high-performance organic afterglow materials obtained by two-component design strategies such as a dopant-matrix, donor-acceptor, sensitization, and energy-transfer strategies. Based on some cutting-edge studies, organic afterglow efficiency has been largely improved, exceeding 90 % in several cases. Organic afterglow durations reach tens of seconds in phosphorescence systems and hours in donor-acceptor systems. Organic afterglow brightness outcompetes some inorganic afterglow materials in the first several seconds after ceasing excitation source. Organic afterglow colors cover the whole visible regions and extend to near-infrared regions with respectful afterglow efficiency. On the basis of these achievements, researchers demonstrate promising applications of organic afterglow materials in diverse fields, which has also been reviewed.

Population genomics reveals that natural variation in PRDM16 contributes to cold tolerance in domestic cattle.

Environmental temperature serves as a major driver of adaptive changes in wild organisms. To discover the mechanisms underpinning cold tolerance in domestic animals, we sequenced the genomes of 28 cattle from warm and cold areas across China. By characterizing the population structure and demographic history, we identified two genetic clusters, i.e., northern and southern groups, as well as a common historic population peak at 30 kilo years ago. Genomic scan of cold-tolerant breeds determined potential candidate genes in the thermogenesis-related pathways that were under selection. Specifically, functional analysis identified a substitution of PRDM16 (p.P779L) in northern cattle, which maintains brown adipocyte formation by boosting thermogenesis-related gene expression, indicating a vital role of this gene in cold tolerance. These findings provide a basis for genetic variation in domestic cattle shaped by environmental temperature and highlight the role of reverse mutation in livestock species.

Demonstration of negative refraction induced by synthetic gauge fields.

Negative refraction is a counterintuitive wave phenomenon that has inspired the development of metamaterials and metasurfaces with negative refractive indices and surface phase discontinuities, respectively. Recent theories have proposed an alternative mechanism for negative refraction: Synthetic gauge fields, induced by either dynamical modulation or motion, can shift a material's dispersion in momentum space, forcing a positive refractive index medium to exhibit negative refraction above a certain threshold. However, this phenomenon has not previously been observed. Here, we report on the experimental demonstration of gauge field­induced negative refraction in a twisted bilayer acoustic metamaterial. The synthetic gauge fields arise in a projected two-dimensional geometry and can be continuously tuned by varying the wave number along the third dimension. Gauge field­induced waveguiding with backward-propagating modes is also demonstrated in a trilayer configuration. These results introduce a mechanism for performing wave manipulation in artificially engineered materials.

Low-Frequency, Open, Sound-Insulation Barrier by Two Oppositely Oriented Helmholtz Resonators.

In this work, a low-frequency, open, sound-insulation barrier, composed of a single layer of periodic subwavelength units (with a thickness of λ/28), is demonstrated both numerically and experimentally. Each unit was constructed using two identical, oppositely oriented Helmholtz resonators, which were composed of a central square cavity surrounded by a coiled channel. In the design of the open barrier, the distance between two adjacent units was twice the width of the unit, showing high-performance ventilation, and low-frequency sound insulation. A minimum transmittance of 0.06 could be observed around 121.5 Hz, which arose from both sound reflections and absorptions, created by the coupling of symmetric and asymmetric eigenmodes of the unit, and the absorbed sound energy propagating into the central cavity was greatly reduced by the viscous loss in the channel. Additionally, by introducing a multilayer open barrier, a broadband sound insulation was obtained, and the fractional bandwidth could reach approximately 0.19 with four layers. Finally, the application of the multilayer open barrier in designing a ventilated room was further discussed, and the results presented an omnidirectional, broadband, sound-insulation effect. The proposed open, sound-insulation barrier with the advantages of ultrathin thickness; omnidirectional, low-frequency sound insulation; broad bandwidth; and high-performance ventilation has great potential in architectural acoustics and noise control.

Observation of Dislocation-Induced Topological Modes in a Three-Dimensional Acoustic Topological Insulator.

The interplay between real-space topological lattice defects and the reciprocal-space topology of energy bands can give rise to novel phenomena, such as one-dimensional topological modes bound to screw dislocations in three-dimensional topological insulators. We obtain direct experimental observations of dislocation-induced helical modes in an acoustic analog of a weak three-dimensional topological insulator. The spatial distribution of the helical modes is found through spin-resolved field mapping, and verified numerically by tight-binding and finite-element calculations. These one-dimensional helical channels can serve as robust waveguides in three-dimensional media. Our experiment paves the way to studying novel physical modes and functionalities enabled by topological lattice defects in three-dimensional classical topological materials.

Acoustic non-Hermitian skin effect from twisted winding topology.

The recently discovered non-Hermitian skin effect (NHSE) manifests the breakdown of current classification of topological phases in energy-nonconservative systems, and necessitates the introduction of non-Hermitian band topology. So far, all NHSE observations are based on one type of non-Hermitian band topology, in which the complex energy spectrum winds along a closed loop. As recently characterized along a synthetic dimension on a photonic platform, non-Hermitian band topology can exhibit almost arbitrary windings in momentum space, but their actual phenomena in real physical systems remain unclear. Here, we report the experimental realization of NHSE in a one-dimensional (1D) non-reciprocal acoustic crystal. With direct acoustic measurement, we demonstrate that a twisted winding, whose topology consists of two oppositely oriented loops in contact rather than a single loop, will dramatically change the NHSE, following previous predictions of unique features such as the bipolar localization and the Bloch point for a Bloch-wave-like extended state. This work reveals previously unnoticed features of NHSE, and provides the observation of physical phenomena originating from complex non-Hermitian winding topology.

Gaining New Insights into Trace Guest Doping Role in Manipulating Organic Crystal Phosphorescence.

Trace guest doping systems often show better room temperature phosphorescence (RTP), but trace guest doping role and mechanism are not recognized well. Here we cocrystallize commercial (CCZ) and self-made (LCZ) carbazole derivatives and verify that 0.2‰ isomer doping can afford the deserved crystal RTP, but further increasing the isomer amount hardly improves RTP. Isomer doping does not affect crystal stacking modes and intermolecular interactions and is inefficient in monomolecular and amorphous states. LCZ derivatives are intrinsically phosphorescent, but crystallization itself cannot effectively inhibit thermal deactivation, and isomer doping restricts nonradiative relaxation and reduces the energy level of the triplet emissive state via space action at a distance rather than currently described adjacent intermolecular interactions. This work has updated some existing views and represented an important conceptual advance in a fresh understanding of trace guest doping RTP systems.

Acoustic Bessel Vortex Beam by Quasi-Three-Dimensional Reflected Metasurfaces.

Vortex beams have a typical characteristic of orbital angular momentum, which provides a new degree of freedom for information processing in remote communication and a form of non-contact manipulation for trapping particles. In acoustics, vortex beams are generally observed on the surface of a metamaterial structure or in a waveguide with a hard boundary owing to the characteristic of easy diffusion in free space. The realization of an acoustic vortex beam with a long-distance propagation in free space still remains a challenge. To overcome this, we report a type of acoustic Bessel vortex (ABV) beam created by a quasi-three-dimensional reflected metasurface in free space based on phase modulation. By using the Bessel and vortex phase profiles, we can realize an ABV beam with the high performances of both Bessel and vortex beams, and its effective propagation distance is larger than 9.2λ in free space. Beyond that, we discuss the bandwidth and topological charge of the ABV beam in detail, and the fractional bandwidth can reach about 0.28. The proposed ABV beam has the advantages of a high-performance vortex, long-distance propagation, and broad bandwidth, which provide a new pathway for designing multifunctional vortex devices with promising applications.