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Abstract Background Oral submucous fibrosis (OSF) is a precancerous lesion characterized by fibrous tissue deposition, the incidence of which correlates positively with the frequency of betel nut chewing. Prolonged betel nut chewing can damage the integrity of the oral mucosal epithelium, leading to chronic inflammation and local immunological derangement. However, currently, the underlying cellular events driving fibrogenesis and dysfunction are incompletely understood, such that OSF has few treatment options with limited therapeutic effectiveness. Dental pulp stem cells (DPSCs) have been recognized for their anti-inflammatory and anti-fibrosis capabilities, making them promising candidates to treat a range of immune, inflammatory, and fibrotic diseases. However, the application of DPSCs in OSF is inconclusive. Therefore, this study aimed to explore the pathogenic mechanism of OSF and, based on this, to explore new treatment options. Methods A human cell atlas of oral mucosal tissues was compiled using single-cell RNA sequencing to delve into the underlying mechanisms. Epithelial cells were reclustered to observe the heterogeneity of OSF epithelial cells and their communication with immune cells. The results were validated in vitro, in clinicopathological sections, and in animal models. In vivo, the therapeutic effect and mechanism of DPSCs were characterized by histological staining, immunohistochemical staining, scanning electron microscopy, and atomic force microscopy. Results A unique epithelial cell population, Epi1.2, with proinflammatory and profibrotic functions, was predominantly found in OSF. Epi1.2 cells also induced the fibrotic process in fibroblasts by interacting with T cells through receptor-ligand crosstalk between macrophage migration inhibitory factor (MIF)-CD74 and C-X-C motif chemokine receptor 4 (CXCR4). Furthermore, we developed OSF animal models and simulated the clinical local injection process in the rat buccal mucosa using DPSCs to assess their therapeutic impact and mechanism. In the OSF rat model, DPSCs demonstrated superior therapeutic effects compared with the positive control (glucocorticoids), including reducing collagen deposition and promoting blood vessel regeneration. DPSCs mediated immune homeostasis primarily by regulating the numbers of KRT19 + MIF + epithelial cells and via epithelial-stromal crosstalk. Conclusions Given the current ambiguity surrounding the cause of OSF and the limited treatment options available, our study reveals that epithelial cells and their crosstalk with T cells play an important role in the mechanism of OSF and suggests the therapeutic promise of DPSCs.

When disturbed, the interaction between power grid and wind farm may cause serious sub/super-synchronous oscillation (SSO), affecting the security and stability of the system. It is therefore important to detect the time-varying amplitude and frequency of SSO to provide information for its control. The matching synchroextracting wavelet transform (MSEWT) is a new method proposed in this paper. Based on the original synchrosqueezing wavelet transform, MSEWT uses a synchronous extraction operator to calculate the time-frequency coefficients and a chirp-rate estimation to modify the instantaneous frequency estimation. Thus, MSEWT can improve the concentration degree and reconstruction accuracy of signal time-frequency representation without iterative calculation, and achieves superior noise robustness. After the time-frequency analysis and modal decomposition of the SSO are performed by MSEWT, the amplitudes and frequencies of each oscillation component can be obtained by Hilbert transform (HT). The simulation studies demonstrate that the proposed scheme can accurately identify the modal parameters of SSO even in the case of noise interference, providing a reliable reference for stable operation of power system time-frequency.

Abstract A nanofabricated superconducting quantum interference device (nano-SQUID) is a direct and sensitive flux probe used for magnetic imaging of quantum materials and mesoscopic devices. Due to the functionalities of superconductive integrated circuits, nano-SQUIDs fabricated on chips are particularly versatile, but their spatial resolution has been limited by their planar geometries. Here, we use femtosecond laser 3-dimensional (3D) lithography to print a needle onto a nano-SQUID susceptometer to overcome the limits of the planar structure. The nanoneedle coated with a superconducting shell focused the flux from both the field coil and the sample. We performed scanning imaging with such a needle-on-SQUID (NoS) device on superconducting test patterns with topographic feedback. The NoS showed improved spatial resolution in both magnetometry and susceptometry relative to the planarized counterpart. This work serves as a proof-of-principle for integration and inductive coupling between superconducting 3D nanostructures and on-chip Josephson nanodevices.

Aiming at the application requirements of underwater cross-domain communication, based on the equivalent relationship between the rotating permanent magnet and the orthogonal time-varying current loop, this paper establishes an air-seawater-seabed three-layer medium model and analyzes the magnetic field distribution and propagation characteristics of the rotating permanent magnet-based mechanical antenna (RMBMA). Based on the electromagnetic field simulation software FEKO, the influence of vertical rotation and horizontal rotation of RMBMA on the radiation magnetic field is analyzed. The magnetic field distribution and magnetic field attenuation characteristics of RMBMA at different depths are obtained by simulation. The influence of RMBMA operating frequency and magnetic moment on the propagation characteristics is studied. The research shows that the horizontal rotation of the magnetic source is better than the vertical rotation in the long-distance underwater communication. When the magnetic source and the receiving point are close to the interface of the medium, the magnetic field strength and the propagation distance can be relatively increased. With appropriate frequency and magnetic moment, the magnetic field strength and communication distance can be further increased.

This paper proposes a two-dimensional signal detection algorithm for low-frequency signal receiving using orthogonal magnetic antenna. According to the directional properties of a single antenna, the direction coefficient is introduced into the model. The algorithm based on Markov Chain Monte Carlo (MCMC) method can accurately estimate the direction coefficient and parameters of the noise in order to perform signal detection. The results show that the proposed algorithm is less affected by the direction of arrival and performs better, in terms of bit error rate, than that based on one-dimensional model. This study provides a valuable reference to omni-directional receiving of signals in low-frequency communication.

The western United States (U.S.) has been experiencing more severe wildfires, in part due to climate change, but the underlying synoptic patterns and their modulation in driving fire weather is unclear. Here we investigated the relationship between weather regimes (WRs) and fire weather indices, specifically vapor pressure deficit (VPD) and the Canadian Forest Fire Weather Index. By identifying five singular WRs using k-means clustering, we found that a particular regime (WR-2), one characterized by a distinct tripolar wave train pattern over the continental U.S., has exhibited an increased frequency since 1980. The ascribed WR-2 regime was found to be mainly responsible for rising trends in the fire weather indices, especially VPD. Further, the average fire indices of the WR-2 regime played a more important role than the frequency in shaping the rising trends in the fire weather indices. The increased frequency of the WR-2 WR was mainly attributed to anthropogenic forcing and, the year-to-year variation of the frequency was associated with sea surface temperature anomalies over the subtropical eastern Pacific. Human-induced climate change might have furthered the exacerbation of wildfire danger in the western U.S. by modulating the behaviors of WRs and fire weather indices.

This paper uses the Lotka-Volterra model to illustrate the synergistic relationship between urbanization and water resources utilization efficiency. Combined with a multi-choice goal programming model, the ideal cooperation coefficient between urbanization and water resources utilization efficiency in each provincial region was calculated under the condition of a coordination equilibrium. The results show that the urbanization level of China's provincial regions is uneven. The urbanization level of the eastern coastal developed areas is the highest, followed by the central area, and the western area is the lowest. Guangdong, Jiangsu, Zhejiang, Shanghai, Beijing and Shandong are at a high level of urbanization. The total factor productivity (tfp) of two-thirds of the provincial regions changed to be >1. During the observation period, water use efficiency of most provinces in China improved. The distribution characteristics of urbanization level and water resources utilization efficiency are not consistent. There is no mutually beneficial relationship between urbanization and water resources utilization in most provincial regions. In a few areas, there is a partial benefit cooperation relationship between them. There is a mutually beneficial relationship in a few regions but the level of coordination in the provincial Chinese mainland is relatively low, and needs to be improved. HIGHLIGHTS Uses the Lotka-Volterra model to study the coordination between urbanization and water resources utilization.; Uses a multi-choice goal programming model to evaluate their coordination.; Evaluates the efficiency of water use in China and provides a theoretical reference for the government to adopt appropriate policies.;

Abstract This study aimed to develop biodegradable calcium alginate microcarriers with uniform particle size and spherical integrity for sustained-release targeting transarterial chemoembolization. To determine related parameters including the ratio of cross-linking volume (sodium alginate: CaCl2), concentrations of sodium alginate and CaCl2 solutions, collection distance, flow rate, stirring speed, syringe needle diameter and hardening time to fabricate the microcarriers, the Taguchi method was applied. Using different conditions, a total of 18 groups were prepared. The average size of microspheres from different groups was estimated as ~ 2 mm (range 1.1 to 1.6 mm). Signal-to-noise ratio analysis showed the optimal spherical integrity (F1) achieved when the above parameters were designed as 0.1, 2.5 wt%, 6 wt%, 8 cm, 30 mL/h, 150 rpm, 0.25 mm and 2 h, respectively. The best (F1), middle (F2) and worst (F3) groups were used for further experiments. Fourier-transform infrared spectroscopy spectrum showed that F1, F2 and F3 conformations were distinct from original sodium alginate. Drug-loaded calcium alginate microcarriers demonstrated rougher surfaces compared to microspheres without drug under transmission electron microscopy. Compared to pH 7.4, swelling rates in PBS were decreased at pH 6.5. Encapsulation and loaded efficiencies of the Dox-loaded microcarriers were estimated as ~ 40.617% and ~ 3.517%. In vitro experiments indicated that the F1 Dox-loaded microcarriers provide a well sustained-release efficacy for about two weeks at 37 °C in PBS. Treatments of calcium alginate microcarriers without the Dox in two distinct hepatocellular carcinoma-derived cell lines, Huh-7 and Hep-3B, indicated that these microcarriers were non-toxic. The Dox-loaded microcarriers displayed sustained-release capacity and reduced cell viabilities to ~ 30% in both cell lines on Day 12.

Objective This study was conducted to fathom the underlying mechanisms of nutrition intervention and redox sensitive transcription factors regulated by Antrodia cinnamomea fermented product (FAC) dietary supplementation in broiler chickens. Methods Four hundreds d-old broilers (41±0.5 g/bird) assigned to 5 groups were examined after consuming control diet, or control diet replaced with 5% wheat bran (WB), 10% WB, 5% FAC, and 10% FAC. Liver mRNA expression of antioxidant, inflammatory and lipid metabolism pathways were analyzed. Prostaglandin E2 (PGE2) concentration in each group were tested in the chicken peripheral blood mononuclear cells (cPBMCs) of 35-d old broilers to represent the stress level of the chickens. Furthermore, these cells were stimulated with 2,2′-Azobis(2-amidinopropane) dihydrochloride (AAPH) and lipopolysaccharide (LPS) to evaluate the cell stress tolerance by measuring cell viability and oxidative species. Results Heme oxygenase-1, glutathione S-transferase, glutamate-cysteine ligase, catalytic subunit, and superoxide dismutase, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that regulates the above antioxidant genes were all up-regulated significantly in FAC groups. Reactive oxygen species modulator protein 1 and NADPH oxygenase 1 were both rather down-regulated in 10% FAC group as comparison with two WB groups. Despite expressing higher level than control group, birds receiving diet containing FAC had significantly lower expression level in nuclear factor-kappa B (NF-κB) and other genes (inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3, and cyclooxygenase 2) involving in inflammatory pathways. Additionally, except for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase that showed relatively higher in both groups, the WB, lipoprotein lipase, Acetyl-CoA carboxylase, fatty acid synthase, fatty acid binding protein, fatty acid desaturase 2 and peroxisome proliferator-activated receptor alpha genes were expressed at higher levels in 10% FAC group. In support of above results, promoted Nrf2 and inhibited NF-κB nuclear translocation in chicken liver were found in FAC containing groups. H2O2 and NO levels induced by LPS and AAPH in cPBMCs were compromised in FAC containing diet. In 35-d-old birds, PGE2 production in cPBMCs was also suppressed by the FAC diet. Conclusion FAC may promote Nrf2 antioxidant pathway and positively regulate lipid metabolism, both are potential inhibitor of NF-κB inflammatory pathway.

Objective This study was investigated the effects of dietary supplementation of Antrodia cinnamomea fermented product on modulation of antioxidation, anti-inflammation, and lipid metabolism in broilers. Methods Functional compounds and in vitro antioxidant capacity were detected in wheat bran (WB) solid-state fermented by Antrodia cinnamomea for 16 days (FAC). In animal experiment, 400 d-old broiler chickens were allotted into 5 groups fed control diet, and control diet replaced with 5% WB, 10% WB, 5% FAC, and 10% FAC respectively. Growth performance, intestinal microflora, serum antioxidant enzymes and fatty acid profiles in pectoral superficial muscle were measured. Results Pretreatment with hot water extracted fermented product significantly reduced chicken peripheral blood mononuclear cells death induced by lipopolysaccharide and 2,2′-Azobis(2-amidinopropane) dihydrochloride. Birds received 5% and 10% FAC had higher weight gain than WB groups. Cecal coliform and lactic acid bacteria were diminished and increased respectively while diet replaced with FAC. For FAC supplemented groups, superoxide dismutase (SOD) activity increased at 35 days only, with catalase elevated at 21 and 35 day. Regarding serum lipid parameters, 10% FAC replacement significantly reduced triglyceride and low-density lipoprotein level in chickens. For fatty acid composition in pectoral superficial muscle of 35-d-old chickens, 5% and 10% FAC inclusion had birds with significantly lower saturated fatty acids as compared with 10% WB group. Birds on the 5% FAC diet had a higher degree of unsaturation, followed by 10% FAC, control, 5% WB, and 10% WB. Conclusion In conclusion, desirable intestinal microflora in chickens obtaining FAC may be attributed to the functional metabolites detected in final fermented product. Moreover, antioxidant effects observed in FAC were plausibly exerted in terms of improved antioxidant enzymes activities, increased unsaturated degree of fatty acids in chicken muscle and better weight gain in FAC inclusion groups, indicating that FAC possesses promising favorable mechanisms worthy to be developed.

Vortices are topological defects of type-II superconductors in an external magnetic field. In a similar fashion to a quantum anomalous Hall insulator, quantum anomalous vortices (QAV) spontaneously nucleate due to orbital-and-spin exchange interaction between supercurrent and magnetic impurity moment without an external magnetic field. Here, we used scanning superconducting quantum interference device microscopy (sSQUID) to search for its signatures in iron-chalcogenide superconductor Fe(Se,Te). Under zero magnetic field, we found a stochastic distribution of isolated anomalous vortices and antivortices with flux quanta Φ_{0}. By applying a small local magnetic field under the coil of the nano-SQUID device, we observed hysteretic flipping of the vortices reminiscent of the switching of ferromagnetic domains, suggesting locally broken time-reversal symmetry. We further observed vectorial rotation of a flux line linking a vortex-antivortex pair by manipulating the local field. These unique properties of the anomalous vortices satisfy the defining criteria of QAV. Our observation suggests an emergent quantum phase with spontaneously nucleated vortex-antivortex matter in an iron-based superconductor with nontrivial topological band structure.

By applying density functional theory combined with nonequilibrium Green’s function, we investigate the electronic and transport properties of V-doped zigzag phosphorene nanoribbons (ZPNRs) with different edge passivations. The results show that the electronic and transport properties of vanadium-doped ZPNRs (V-ZPNRs) can be tuned by the edge passivation types. V-ZPNRs passivated by sulfur atoms possess stronger conductivity than bared ones, and edge passivation by hydrogen and halogen (F and Cl) atoms can transform V-ZPNRs from magnetic metals to magnetic semiconductors. Moreover, due to the edge passivation by hydrogen and halogen atoms, V-ZPNRs exhibit dual spin polarizability and negative differential resistance effects. The findings provide theoretical support in modulating the electronic transport properties of ZPNRs, which may be useful in designing phosphorene-based spintronic devices.

Layered perovskite oxides A3B2O7 with Ruddlesden–Popper structures have attracted great attention due to their intriguing hybrid improper ferroelectricity. In this work, we prepared high-quality epitaxial Ca3Ti2O7 (CTO) thin films on Nb-SrTiO3 (STO) and Pt–Si substrates by pulsed laser deposition. The epitaxial relationship between the CTO thin film and Nb-STO substrate is [010]CTO//[010]Nb-STO, while the CTO film on Pt–Si is the polycrystalline growth with the preferred orientation of (010). The piezoelectric force microscopy image is attested to the stable existence of ferroelectricity in CTO films at room temperature with different growth patterns. A resistive switching behavior with at least two orders of magnitude is observed in CTO films driven by their ferroelectric polarization reversal. Moreover, a downward self-poling phenomenon is observed in CTO films on different substrates, and the flexoelectric effect induced by the strain gradient is supposed to be the main origin.

This Covid-19 pandemic has been a trying time for all countries, governments, societies, and individuals. The physical, social, and organizational infrastructure of healthcare systems across the world is being stressed. This pandemic has highlighted that the healthcare of the country is as strong as its weakest link and that no aspect of life, be it social or economic, is spared from this pandemic. The authors would like to highlight some of the lessons learned from Singapore’s management of the Covid-19 pandemic. During the Singaporean Covid-19 pandemic, public health policy planning was all encompassing in its coverage, involving various stakeholders in government and society. The important role of individuals, governments, industry, and primary healthcare practitioners when tackling COVID-19 are highlighted. Singapore’s management of the Covid-19 pandemic involved an approach that involved the whole of society, with a particular focus on supporting the vulnerable foreign worker population, which formed the majority of Covid-19 cases in the country. Hopefully amidst the trying times, valuable lessons are learnt that will be etched into medical history and collective memory. We hope to highlight these lessons for future generations, both for members of the public and fellow healthcare practitioners.

Co–Cr–W alloys were widely used in the inlet exhaust valve of aeroengine. However, the traditional manufacturing process of Co–Cr–W alloys can not meet the demand for higher comprehensive performance, and an optimum method needs to be developed. Herein, a Co–Cr–W alloy reinforced by exogenous carbides was prepared by the powder metallurgy method. Effect of ball-milling time on the microstructure and wear resistance of the alloy was investigated, and the formation mechanisms of the reinforcing phases were discussed. Results showed that with prolonging the ball-milling time, the uniformity of the reinforcing phases was improved, grain refinement was achieved, the hardness increased, a suitable bonding interface was formed between the matrix and reinforcing phases, and better wear resistance was thus achieved. However, when the ball-milling time increased from 60 h to 70 h, local segregation of the reinforcing phases occurred, the hardness decreased from 64 HRC to 60 HRC, and the friction coefficient increased from 0.53 to 0.58. Based on our experimental results, we proposed two formation mechanisms of the reinforcing phases (carbides): In-situ precipitation from the matrix and in situ autogenic reaction between the elements of the matrix and the added carbides (WC and Cr _3 C _2 particles). Both mechanisms contributed to the formation of M _23 C _6 and M _6 C carbides. Our results underscore the importance of added reinforcing phases and help to optimize the ball-milling process in preparing the Co–Cr–W alloys.

Speech variability facilitates non-tonal language speakers’ lexical tone learning. However, it remains unknown whether tonal language speakers can also benefit from speech variability while learning second language (L2) lexical tones. Researchers also reported that the effectiveness of speech variability was only shown on learning new items. Considering that the first language (L1) and L2 probably share similar tonal categories, the present study hypothesizes that speech variability only promotes the tonal language speakers’ acquisition of L2 tones that are different from the tones in their L1. To test this hypothesis, the present study trained native Mandarin (a tonal language) speakers to learn Cantonese tones with either high variability (HV) or low variability (LV) speech materials, and then compared their learning performance. The results partially supported this hypothesis: only Mandarin subjects’ productions of Cantonese low level and mid level tones benefited from the speech variability. They probably relied on the mental representations in L1 to learn the Cantonese tones that had similar Mandarin counterparts. This learning strategy limited the impact of speech variability. Furthermore, the results also revealed a discrepancy between L2 perception and production. The perception improvement may not necessarily lead to an improvement in production.