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To address the issue of insufficient carbon sources in urban sewage, which leads to poor nitrogen removal performance in sewage treatment systems, an anaerobic/anoxic/aerobic (AAO) pilotscale reactor was established. The reactor aimed to treat low C/N (chemical oxygen demand; COD/total nitrogen; TN) municipal wastewater (C/N<5). To enhance nitrogen removal and investigate the mechanism in the AAO process, a Pall ring modified biological suspended filler was introduced to the aerobic zone after achieving partial nitrification and denitrification (PND). The results revealed that the activated sludge-biofilm composite system can be successfully formed within 40 days, with a stable loaded biomass on the membrane at 40.06 mg/g (measured by volatile suspended solids (VSS)/filler). The aerobic zone of the activated sludge-biofilm composite system demonstrated an increase in nitrite accumulation rate (NAR) and simultaneous nitrification and denitrification efficiency (SND), from 60.46% and 19.42% in the initial stage (stage 1) to 69.62% and 46.47% in the stable forming stage (stage 3), respectively. By promoting both PND and SND pathways for nitrogen removal, the effluent from the system exhibited decreased concentrations of ammonia nitrogen (NH4+-N) at 0.11 mg/L and total nitrogen (TN) at 4.55 mg/L, indicating the significant synergistic effect of the biofilm on nitrogen removal. 16S rRNA amplification and sequencing analysis revealed that Proteobacteria was the dominant microorganism in the 60-day biofilm, accounting for 76.12% of the relative abundance. The main ammonia oxidizing bacteria (AOB) were Nitrosomanas (1.77%) and Nitrosococcus (1.69%). Meanwhile, denitrification microbial species were found to have a substantial proportion (29.11%), along with a small amount of Anammox bacteria (Anammoxoglobus, 0.35%) within the biofilm. These sequencing results were consistent with the macroscopic performance of the reactor. Overall, these findings establish a theoretical foundation for enhancing nitrogen removal in the AAO system. [ABSTRACT FROM AUTHOR]

Rationale: Recently N-Fluoroarenesulfonamides (ArSO2NHF) were found to be promising precursors for the preparation of N-fluorobenzenesulfonimide derivatives without applying F2. However, very few studies have discussed the mass spectrometric behaviors of ArSO2NHF with N-F structure. Methods: In this article, we applied high-resolution electrospray ionization tandem mass spectrometry (HR-ESI-MS/MS) to study the effect on the mass spectrometric behaviors of ArSO2NHF after the introduction of the F-atom to the N-atom of ArSO2NH2. Results: High-resolution electrospray ionization mass spectrometry (HR-ESI-MS) experiments showed that ArSO2NHF produced only good signals in negative ion mode, and the dominating product ion SO2F- at m/z 83 was observed in all HR-ESIMS/MS of ArSO2NF- with different substituents in the Ar group. The formation of the product ion SO2F- was proof of the gas-phase F-atom migration rearrangement from the N-atom to the S-atom in ESI-MS/MS of ArSO2NF-. Conclusion: To fully explain the gas-phase reaction mechanism from ArSO2NF- to SO2F-, we studied the HR-ESI-MS/MS of deprotonated ArSO2NHF and also performed theoretical calculations. Both results confirmed that ArSO2NF- first underwent Smiles rearrangement to yield intermediate I (INT1) ArNFSO2-, and then the F-atom of ArNFSO2- migrated from the N-atom to the S-atom to form intermediate II (INT2) ArN-SO2F, which finally dissociated to SO2F- at m/z 83 with loss of a neutral nitrene (ArN). All these results showed that the formation of the product ion SO2F- from ArSO2NF- was a common and intrinsic gas-phase reactivity of ArSO2NF-. [ABSTRACT FROM AUTHOR]

The cracks in Al2O3-ZrO2 eutectic ceramics produced by laser powder bed fusion (LPBF) have a significant impact on their practical applications in various industries. In order to understand the factors influencing crack formation, a systematic study of the characterization and propagation of cracks in single-track, multitrack, and bulk samples by varying the process parameters has been carried out in this research. The results showed that parallel cracks can be healed by reducing the scanning spacing and scanning length. Additionally, it was found that using a modest scanning speed and a shorter length can minimize the accumulation of thermal stress, resulting in the suppress crack formation. Based on this conclusion, a crack-free Al2O3-ZrO2 eutectic ceramic sample was finally obtained under the optimized parameters with the power of 100 W, the scanning speed of 100 mm/s, the hatch spacing of 100 µm, the scanning length of 3 mm, and the layer thickness of 50 µm. Additionally, three typical microstructures, including eutectic, cellular, and dendritic structures, were identified in the LPBF-fabricated Al2O3-ZrO2 samples. The cellular microstructure showed improved crack inhibition capability due to the deflection and pinning effects. Cracks expand more easily in dendritic and eutectic microstructures, where anisotropy is more prominent. [ABSTRACT FROM AUTHOR]

Auditory dorsal and ventral pathways in the human brain play important roles in supporting speech and language processing. However, the evolutionary root of the dual auditory pathways in the primate brain is unclear. By parcellating the auditory cortex of marmosets (a New World monkey species), macaques (an Old World monkey species), and humans using the same individual-based analysis method and tracking the pathways from the auditory cortex based on multi-shell diffusion-weighted MRI (dMRI), homologous auditory dorsal and ventral fiber tracks were identified in these primate species. The ventral pathway was found to be well conserved in all three primate species analyzed but extend to more anterior temporal regions in humans. In contrast, the dorsal pathway showed a divergence between monkey and human brains. First, frontal regions in the human brain have stronger connections to the higher-level auditory regions than to the lower-level auditory regions along the dorsal pathway, while frontal regions in the monkey brain show opposite connection patterns along the dorsal pathway. Second, the left lateralization of the dorsal pathway is only found in humans. Moreover, the connectivity strength of the dorsal pathway in marmosets is more similar to that of humans than macaques. These results demonstrate the continuity and divergence of the dual auditory pathways in the primate brains along the evolutionary path, suggesting that the putative neural networks supporting human speech and language processing might have emerged early in primate evolution. [ABSTRACT FROM AUTHOR]

As a prototypical photocatalyst, TiO2 has been extensively studied. An interesting yet puzzling experimental fact was that P25—a mixture of anatase and rutile TiO2— outperforms the individual phases; the origin of this mysterious fact, however, remains elusive. Employing rigorous first-principles calculations, here we uncover a metastable intermediate structure (MIS), which is formed due to confinement at the anatase/rutile interface. The MIS has a high conduction-band minimum level and thus substantially enhances the overpotential of the hydrogen evolution reaction. Also, the corresponding band alignment at the interface leads to efficient separation of electrons and holes. The interfacial confinement additionally creates a wide distribution of the band gap in the vicinity of the interface, which in turn improves optical absorption. These factors all contribute to the enhanced photocatalytic efficiency in P25. Our insights provide a rationale to the puzzling superior photocatalytic performance of P25 and enable a strategy to achieve highly efficient photocatalysis via interface engineering. [ABSTRACT FROM AUTHOR]

Persistent high-risk HPV infection is closely associated with cervical cancer development, and there is no drug targeting HPV on the market at present, so it is particularly important to understand the interaction mechanism between HPV and the host which may provide the novel strategies for treating HPV diseases. HPV can hijack cell surface heparan sulfate proteoglycans (HSPGs) as primary receptors. However, the secondary entry receptors for HPV remain elusive. We identify myosin-9 (NMHC-IIA) as a host factor that interacts with HPV L1 protein and mediates HPV internalization. Efficient HPV entry required myosin-9 redistribution to the cell surface regulated by HPV-hijacked MEK-MLCK signaling. Myosin-9 maldistribution by ML-7 or ML-9 significantly inhibited HPV pseudoviruses infection in vitro and in vivo. Meanwhile, N-glycans, especially the galactose chains, may act as the decoy receptors for HPV, which can block the interaction of HPV to myosin-9 and influence the way of HPV infection. Taken together, we identify myosin-9 as a novel functional entry receptor for high-risk HPV both in vitro and in vivo, and unravel the new roles of myosin-9 and N-glycans in HPV entry, which provides the possibilities for host targets of antiviral drugs. [ABSTRACT FROM AUTHOR]

Senile osteoporosis increases fracture risks. Bone marrow stromal cells (BMSCs) are sensitive to aging. Deep insights into BMSCs aging are vital to elucidate the mechanisms underlying age-related bone loss. Recent advances showed that osteoporosis is associated with aberrant DNA methylation of many susceptible genes. Galectin-1 (Gal-1) has been proposed as a mediator of BMSCs functions. In our previous study, we showed that Gal-1 was downregulated in aged BMSCs and global deletion of Gal-1 in mice caused bone loss via impaired osteogenesis potential of BMSCs. Gal-1 promoter is featured by CpG islands. However, there are no reports concerning the DNA methylation status in Gal-1 promoter during osteoporosis. In the current study, we sought to investigate the role of DNA methylation in Gal-1 downregulation in aged BMSCs. The potential for anti-bone loss therapy based on modulating DNA methylation is explored. Our results showed that Dnmt3b-mediated Gal-1 promoter DNA hypermethylation plays an important role in Gal-1 downregulation in aged BMSCs, which inhibited β-catenin binding on Gal-1 promoter. Bone loss of aged mice was alleviated in response to in vivo deletion of Dnmt3b from BMSCs. Finally, when bone marrow of young wild-type (WT) mice or young Dnmt3bPrx1-Cre mice was transplanted into aged WT mice, Gal-1 level in serum and trabecular bone mass were elevated in recipient aged WT mice. Our study will benefit for deeper insights into the regulation mechanisms of Gal-1 expression in BMSCs during osteoporosis development, and for the discovery of new therapeutic targets for osteoporosis via modulating DNA methylation status. NEW & NOTEWORTHY There is Dnmt3b-mediated DNA methylation in Gal-1 promoter in aged bone marrow stromal cell (BMSC). DNA methylation causes Gal-1 downregulation and osteogenesis attenuation of aged BMSC. DNA methylation blocks β-catenin binding on Gal-1 promoter. Bone loss of aged mice is alleviated by in vivo deletion of Dnmt3b from BMSC. [ABSTRACT FROM AUTHOR]

Shahe Reservoir is a key node in the upstream of the North Canal, and the water quality has gradually improved after the implementation of low water operation in 2018. The organic matter(OM) in the sediment decreased from 16.66 to 14.22%.In this study, the FI index and parallel factor method were used to investigate the traceability of OM and dissolved organic matter (DOM) in the Shahe Reservoir before and during low water level operation(LWLO), and the results showed that the terrestrial source fraction of OM in sediments was mainly related to organic-rich terrestrial plant residues carried by tributaries and overflows/outfalls during the rainy season, and the FI index indicated that the organic matter (OM) in the Shahe Reservoir before and during LWLO in each DOM in the area is derived from authigenic sources of autotrophic microorganisms, algae, etc. The parallel factor method shows that more than most of the pollutants in the DOM are input from endogenous sources and a small proportion of pollutants are input from exogenous sources. Nutrients in both sediment and interstitial water increased during the LWLO, with TN and TP levels increasing by 262.38 and 204.45 mg·kg−1 in sediment, NH4+–N, PO43−−P, TN and TP in interstitial water increasing by 0.98, 1.36, 2.07 and 4.33 mg·L−1, respectively. Pearson correlation analysis and principal component analysis showed that OM was significantly correlated with nutrients: OM and TN (p < 0.01) and OM and TP (p < 0.05) in the pre-LWLO; OM and TN and TP (p < 0.01) in the LWLO.The results suggested that organic matter pollution control should be mainly carried out from the perspective of endogenous input, focusing on controlling the release of nutrients in sediments. [ABSTRACT FROM AUTHOR]

Phosphoprotein phosphatase 1 (PP1) associates with specific regulatory subunits to achieve, among other functions, substrate selectivity. Among the eight PP1 isotypes in Leishmania, PP1-8e associates with the regulatory protein PNUTS along with the structural factors JBP3 and Wdr82 in the PJW/PP1 complex that modulates RNA polymerase II (pol II) phosphorylation and transcription termination. Little is known regarding interactions involved in PJW/PP1 complex formation, including how PP1-8e is the selective isotype associated with PNUTS. Here, we show that PNUTS uses an established RVxF-ΦΦ-F motif to bind the PP1 catalytic domain with similar interfacial interactions as mammalian PP1-PNUTS and noncanonical motifs. These atypical interactions involve residues within the PP1-8e catalytic domain and N and C terminus for isoform-specific regulator binding. This work advances our understanding of PP1 isoform selectivity and reveals key roles of PP1 residues in regulator binding. We also explore the role of PNUTS as a scaffold protein for the complex by identifying the C-terminal region involved in binding JBP3 and Wdr82 and impact of PNUTS on the stability of complex components and function in pol II transcription in vivo. Taken together, these studies provide a potential mechanism where multiple motifs within PNUTS are used combinatorially to tune binding affinity to PP1, and the C terminus for JBP3 and Wdr82 association, in the Leishmania PJW/PP1 complex. Overall, our data provide insights in the formation of the PJW/PP1 complex involved in regulating pol II transcription in divergent protozoans where little is understood. [ABSTRACT FROM AUTHOR]

This work involves the preparation of WC/Co/Ni blends using different mixing ratios to form Co/Ni/WC composite-based coatings by laser cladding. The effect of each component and their mixtures on the mechanical properties was evaluated using a mixture design approach. The morphologies and microstructures of the laser clads were characterized using a scanning electron microscope and X-ray diffraction techniques. Cracking behavior and fracture based on residual stresses are explored. In addition, the mathematical models between the three-component mixtures and the mechanical properties of the laser clad were established. The results showed that the welds containing 50 % WC-50 % Ni alloys were successfully deposited by laser cladding with favorable mechanical properties. These welds reduced the remarkable fracture crack activities and did not cause delamination in the laser clads. An increase in WC content significantly enhances wear resistance and microhardness, except for the crack susceptibilities in all mixtures. Additionally, when increased Co/Ni on WC, the reduction of adhesive wear is more significant than that of abrasive wear. Wear resistance is improved by the high content of WC particles in the laser-clad joints. Based on the mixture models, better mixed ratios for the blends that were developed using a multi-objective superimposed optimization technique make these blended materials promising candidates and can ensure the quality of laser clads. The findings from this study will greatly contribute to optimizing the blend ratio of the three-ingredient mixture based on mixture design to enhance structural evolution and mechanical properties, and also obtain better quality laser-clad coatings. [ABSTRACT FROM AUTHOR]

Fracturing fluids (FFs) have been widely used to stimulate the tight reservoir. However, current FFs will not only lose their rheological property at high temperatures and high salt but also show an incomplete gel-breaking property. Herein, a double crosslinking network FF with pretty superiorities in rheology and low damage to the core was constructed by introducing both physical crosslinking and chemical crosslinking into the system. The construction of double crosslinking networks enhanced the rheology of this functional FF. The particle sizes of gel-breaking fluids are mainly distributed in 1.0–10,000 nm; furthermore, for every 10,000 mg/L increase in salinity, the particle size of the gel-breaking fluid is decreased by almost half. The adsorption capacity (<1.0 mg/g) gradually decreased with the increase of salinity at 20 °C. Moreover, the adsorption of gel-breaking fluids on the rock decreased first and then kept stable with temperature increasing at a salinity of ≤30,000 mg/L, however, showed the opposite trend at 40,000 mg/L. The results of rheology, particle size, static adsorption, and core damage showed that this functional FF could be an alternative for the stimulation of a tight reservoir with high temperature and recycling of produced water with high salinity. [ABSTRACT FROM AUTHOR]

In this study, cellulose fiber was extracted from bamboo shoot shell with a deep eutectic solvent (DES). The deep eutectic solvent used was prepared by the fusion of choline chloride (ChCl), oxalic acid (OA) and ethylene glycol (EG) at 80 °C. Based on the degumming rate, the influence of temperature and time on the DES degumming system was determined. Based on the scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TG) results, it was confirmed that the DES system can remove colloids from bamboo shoot shell, increasing the thermal stability and heat resistance of bamboo shoot shell fiber, and improving its crystallinity. It was proved that the DES system can effectively remove lignin and hemicelluloses, and retain cellulose in bamboo shoot shell. [ABSTRACT FROM AUTHOR]

Overlook of chiral consideration in transdermal drug delivery increases administrated dose and risk of side effects, decreasing therapeutical effects. To improve the transdermal delivery efficiency of eutomer, this work focused on investigating the law and mechanism of enantioselective enhancing effects of chiral permeation enhancers on drug enantiomers. Chiral nonsteroidal anti-inflammatory drugs and terpene permeation enhancers were selected as model drug and enhancers. The results indicated that the L-isomer of permeation enhancers increased the skin absorption of S-enantiomer of drug and D-isomer improve the permeation of R-enantiomer, in which the enhancement effect (ER) of Lmenthol on S-enantiomer (ER = 3.23) was higher than that on R-enantiomer (ER = 1.49). According to the pharmacokinetics results, L-menthol tended to enhance the permeation of S-enantiomer better than R-enantiomer (2.56 fold), and showed excellent in vitro / in vivo correlations. The mechanism study showed that L-isomer of permeation enhancers improved the permeation of S-enantiomer by increasing the retention, but the D-isomer by improving partition for better permeation. Enantioselective mechanism indicated that the weaker chiral H-bond interaction between drug-chiral enhancers was caused by the enantiomeric conformation. Additionally, stronger chiral enhancers-skin interaction between L-isomer and S-conformation of ceramide produced better enhancing effects. In conclusion, enantioselective interaction of chiral drug-chiral enhancers and chiral enhancers-chiral skin played a critical role in transdermal drug delivery, rational utilization of which contributed to improving the uptake of eutomer and inhibiting distomers to decrease a half of dose and side effects, increasing transdermal therapeutical efficiency. [ABSTRACT FROM AUTHOR]

Purpose: Emotional voice conveys important social cues that demand listeners' attention and timely processing. This event-related potential study investigated the feasibility of a multifeature oddball paradigm to examine adult listeners' neural responses to detecting emotional prosody changes in nonrepeating naturally spoken words. Method: Thirty-three adult listeners completed the experiment by passively listening to the words in neutral and three alternating emotions while watching a silent movie. Previous research documented preattentive change-detection electrophysiological responses (e.g., mismatch negativity [MMN], P3a) to emotions carried by fixed syllables or words. Given that the MMN and P3a have also been shown to reflect extraction of abstract regularities over repetitive acoustic patterns, this study employed a multifeature oddball paradigm to compare listeners' MMN and P3a to emotional prosody change from neutral to angry, happy, and sad emotions delivered with hundreds of nonrepeating words in a single recording session. Results: Both MMN and P3a were successfully elicited by the emotional prosodic change over the varying linguistic context. Angry prosody elicited the strongest MMN compared with happy and sad prosodies. Happy prosody elicited the strongest P3a in the centro-frontal electrodes, and angry prosody elicited the smallest P3a. Conclusions: The results demonstrated that listeners were able to extract the acoustic patterns for each emotional prosody category over constantly changing spoken words. The findings confirm the feasibility of the multifeature oddball paradigm in investigating emotional speech processing beyond simple acoustic change detection, which may potentially be applied to pediatric and clinical populations. [ABSTRACT FROM AUTHOR]

In recommender systems, some features directly affect whether an interaction would happen, making the happened interactions not necessarily indicate user preference. For instance, short videos are objectively easier to finish even though the user may not like the video.We term such feature as confounding feature, and video length is a confounding feature in video recommendation. If we fit a model on such interaction data, just as done by most data-driven recommender systems, the model will be biased to recommend short videos more, and deviate from user actual requirement. This work formulates and addresses the problem from the causal perspective. Assuming there are some factors affecting both the confounding feature and other item features, e.g., the video creator, we find the confounding feature opens a backdoor path behind user-item matching and introduces spurious correlation. To remove the effect of backdoor path, we propose a framework named Deconfounding Causal Recommendation (DCR), which performs intervened inference with do-calculus. Nevertheless, evaluating do-calculus requires to sum over the prediction on all possible values of confounding feature, significantly increasing the time cost. To address the efficiency challenge, we further propose a mixture-of-experts (MoE) model architecture, modeling each value of confounding feature with a separate expert module. Through this way, we retain the model expressiveness with few additional costs. We demonstrate DCR on the backbone model of neural factorization machine (NFM), showing that DCR leads to more accurate prediction of user preference with small inference time cost. [ABSTRACT FROM AUTHOR]

Analysing the temporal and spatial changes in regional rainfall erosivity can reveal the formation mechanism and succession process of water and soil loss. This is particularly relevant for ecologically fragile areas, such as the Tibetan Plateau. In this study, a gravity centre model, Hovmoller diagram, wavelet analysis, Mann-Kendall test, Rescale range analysis, and Daniel's trend test were used to analyse the spatial and temporal evolution pattern of rainfall erosivity on the Tibetan Plateau. The study used 0.25° spatial resolution data based on ERA5 correction from 1950-2020, which improved the spatial resolution and extended the time range of rainfall erosivity research on the Tibetan Plateau. The rainfall erosion in the southeast of the Tibetan Plateau was found to be severe and gradually decreased from the southeast to northwest. The average gravity centre of rainfall erosivity migrated from the southeast to the northwest. Regarding the time cycle, the average rainfall erosivity of the Tibetan Plateau changed rapidly each year, with an approximately 11-year cycle. Furthermore, the rainfall erosivity in the Tibetan Plateau showed a weak downward trend, which could continue to decrease in the future. Collectively, these results support regional ecological security and can help prepare prevention and control measures. [ABSTRACT FROM AUTHOR]

In order to clarify the migration mechanism and wake behavior of a single bubble rising near a vertical wall, three-dimensional direct numerical simulations are implemented based on the open-source software Basilisk and various types of migration paths like linear, zigzag and spiral are investigated. The volume of fluid (VOF) method is used to capture the bubble interface at a small scale, while the gas-liquid interface and high-velocity-gradient regions in the flow field are encrypted with the adaptive mesh refinement technology. The results show that the vertical wall has an obstructive effect on the diffusion of the vortex boundary layer on the surface of the bubble migrating in a straight line, and the resulting reaction force tends to push the bubbles away from the wall surface. For the zigzag or spiral movement of a bubble in the x-y plane, the perpendicular wall is an unstable factor, but on the contrary, the motion in the z-y plane is stabilized. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effects of controlled low central venous pressure combined with dexmedetomidine on the blood loss, renal function and cognitive function in patients undergoing laparoscopic hepatectomy. From January 2021 to October 2022, 90 patients treated with laparoscopic hepatectomy in Huai’an First People’s Hospital were selected as subject objects and equally divided into the study group and control group in a random method. The blood loss, surgical duration, duration of hepatic portal occlusion, serum bilirubin, creatinine, urea nitrogen, hemoglobin, plasma albumin, interleukin (IL)-6 and cognitive function in the two groups were compared. Patients in the study group receiving the combination of controlled low central venous pressure and dexmedetomidine showed less blood loss and shorter time of hepatic portal occlusion as compared to the control group. The levels of serum bilirubin, creatinine and urea nitrogen were significantly increased at postoperative 3 days compared with pre-operation in the study and control groups. In particular, these factors were higher in control group than that in the control group at postoperative 3 days, indicating better liver function and renal function of patients in the study group than those in the control group. The levels of hemoglobin and plasma albumin observed in study group 3 days after surgery were higher than those in the control group. At 1 day after surgery, the level of IL-6 was significantly lower in the study group than that in the control group. Patients in the study group achieved significantly higher mini-mental state examination (MMES) scores than those in the control group at postoperative 1 day, 3 days and 7 days. The controlled low central venous pressure combined with dexmedetomidine is a promising clinical practice in decreasing blood loss, improving the liver and kidney function, and protecting the cognitive function of patients during laparoscopic hepatectomy. [ABSTRACT FROM AUTHOR]

Adult stem cells maintain homeostatic self-renewal through the strategy of either population or single-cell asymmetry, and the former type of stem cells are thought to take passive while the latter ones take active competition for niche occupancy. Although the division ability of stem cells is known to be crucial for their passive competition, whether it is also crucial for active competition is still elusive. Drosophila female germline stem cells are thought to take active competition, and bam mutant germ cells are more competitive than wild-type germline stem cells for niche occupancy. Here we report that either cycB, cycE, cdk2, or rheb null mutation drastically attenuates the division ability and niche occupancy capacity of bam mutant germ cells. Conversely, accelerating their cell cycle by mutating hpo has an enhanced effect. Last but not least, we also determine that E-cadherin, which was proposed to be crucial previously, just plays a mild role in bam mutant germline niche occupancy. Together with previous studies, we propose that division ability plays a unified crucial role in either active or passive competition among stem cells for niche occupancy. [ABSTRACT FROM AUTHOR]

Anisotropic actuation, a universal phenomenon in nature, may be inspiring for the development of intelligent soft robotics in the future. For dielectric elastomers (DEs), important investigations have been done to decrease the voltage and increase the actuation strain. However, mechanical isotropy of synthetic DEs shows in-plane uniform deformation, lacking the controllability of the actuation direction. Herein, an anisotropic DE (denoted as ADE) is constructed by casting Ecoflex/BaTiO3 solution onto oriented TPU nanofibrous membranes fabricated via drum electrospinning. The resulting ADE with a seamless three-layer structure features mechanical anisotropy in the elastic modulus, with the maximum ratio between x and y directions of the plane being 11. A prototype ADE-based actuator demonstrates a high electroactuation anisotropy of 3.95, a large unidirectional length strain of 15%, and a high energy density of 0.014 MJ m-3 at an electric field of 40 V µm-1. Two potential applications, a flow divider valve simulating the Transwell test in the medical field and a mechanical stimulus component mimicking the maturation of cardiomyocytes, are successfully demonstrated. Thus, this work offers a versatile yet simple approach for fabricating anisotropic electroactive elastomer actuators in the future. [ABSTRACT FROM AUTHOR]

Background: CD73 promotes progression in several malignancies and is considered as a novel immune checkpoint. However, the function of CD73 in intrahepatic cholangiocarcinoma (ICC) remains uncertain. In this study, we aim to investigate the role of CD73 in ICC. Methods: Multi-omics data of 262 ICC patients from the FU-iCCA cohort were analyzed. Two single-cell datasets were downloaded to examine the expression of CD73 at baseline and in response to immunotherapy. Functional experiments were performed to explore the biological functions of CD73 in ICC. The expression of CD73 and HHLA2 and infiltrations of CD8 + , Foxp3 + , CD68 + , and CD163 + immune cells were evaluated by immunohistochemistry in 259 resected ICC samples from Zhongshan Hospital. The prognostic value of CD73 was assessed by Cox regression analysis. Results: CD73 correlated with poor prognosis in two ICC cohorts. Single-cell atlas of ICC indicated high expression of CD73 on malignant cells. TP53 and KRAS gene mutations were more frequent in patients with high CD73 expression. CD73 promoted ICC proliferation, migration, invasion, and epithelial-mesenchymal transition. High CD73 expression was associated with a higher ratio of Foxp3 + /CD8 + tumor-infiltrating lymphocytes (TILs) and CD163 + /CD68 + tumor-associated macrophages (TAMs). A positive correlation between CD73 and CD44 was observed, and patients with high CD73 expression showed elevated expression of HHLA2. CD73 expression in malignant cells was significantly upregulated in response to immunotherapy. Conclusions: High expression of CD73 is associated with poor prognosis and a suppressive tumor immune microenvironment in ICC. CD73 could potentially be a novel biomarker for prognosis and immunotherapy in ICC. [ABSTRACT FROM AUTHOR]

We consider an inverse problem arising in nonlinear ultrasound imaging. The propagation of ultrasound waves is modeled by a quasilinear wave equation. We make measurements at the boundary of the medium encoded in the Dirichlet-to-Neumann map and we show that these measurements determine the nonlinearity. [ABSTRACT FROM AUTHOR]

Gastrodia bawanglingensis, a new species of Orchidaceae from Hainan Island, China, is described and illustrated. It is morphologically similar to G. theana, G. albidoides and G. albida with dwarf habits, scarcely opening flowers, elongated fruit stems, curved and fleshy perianth tubes and similar columns and lips, but can be easily distinguished from them by having a pair of lateral wings bent outwards at the apex of the column and lateral wings with acuminate tips lower than the anther. According to the IUCN Red List Categories and Criteria, the new species is assessed as Endangered (EN). The plastome of G. bawanglingensis is greatly reduced and reconfigured with approximately 30876 bp in size and 25.36% in GC content. Morphological characteristics and molecular phylogenetic results based on chloroplast gene sequences support the recognition of G. bawanglingensis as a new species within Gastrodia. [ABSTRACT FROM AUTHOR]

Nanofiltration has gained increasing attention in lithium extraction from salt lake brine with high Mg2+/Li+ ratio. However, conventional nanofiltration membranes with negatively charged surfaces suffer from low Mg2+/Li+ selectivity. Herein, positive nanofiltration membranes with high charge density were fabricated via a two-step charge enhancement strategy. High concentration of polyethylenimine was used as the aqueous monomer to ensure the abundant amino groups on the membrane surface. To further enhance the electro-positivity, 2, 3-epoxypropyl trimethyl ammonium chloride was grafted through ring-opening reactions. The as-obtained membranes demonstrated positive zeta potentials over a large pH range (3-10), leading to significantly strengthened Donnan exclusion for Mg2+. The membrane rejection to MgCl2 was up to 99.3% while the rejection to LiCl was only ∼30%. The Mg2+/Li ​+ ​separation factor was 167 when filtration simulated brine with a Mg2+/Li+ ratio of 20 (2000 ​ppm MgCl2 and LiCl mixture), which is the highest value achieved among polyamide-based nanofiltration membranes. In addition, the membranes exhibited good stability in 40 ​h’ continuous testing. The modification strategy proposed in the present work is highly compatible with current industrial membrane preparation processes and easy to scale up with cost effectiveness. [ABSTRACT FROM AUTHOR]

Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Storeoperated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic plasticity. However, the underlying mechanism of SOCE in mediating neuronal transmitter release and synaptic transmission remains ambiguous in neuropathic pain. Neuropathic rats were operated by spinal nerve ligations. Neurotransmissions were assessed by whole-cell recording in substantia gelatinosa. Immunofluorescence staining of STIM1 with neuronal and glial biomarkers in the spinal dorsal horn. The endoplasmic reticulum stress level was estimated from qRT-PCR. Intrathecal injection of SOCE antagonist SKF96365 dose-dependently alleviated mechanical allodynia in ipsilateral hind paws of neuropathic rats with ED50 of 18 μg. Immunofluorescence staining demonstrated that STIM1 was specifically and significantly expressed in neurons but not astrocytes and microglia in the spinal dorsal horn. Bath application of SKF96365 inhibited enhanced miniature excitatory postsynaptic currents in a dosage-dependent manner without affecting miniature inhibitory postsynaptic currents. Mal-adaption of SOCE was commonly related to endoplasmic reticulum (ER) stress in the central nervous system. SKF96365 markedly suppressed ER stress levels by alleviating mRNA expression of C/ EBP homologous protein and heat shock protein 70 in neuropathic rats. Our findings suggested that nerve injury might promote SOCE-mediated calcium levels, resulting in long-term imbalance of spinal synaptic transmission and behavioral sensitization, SKF96365 produces antinociception by alleviating glutamatergic transmission and ER stress. This work demonstrated the involvement of SOCE in neuropathic pain, implying that SOCE might be a potential target for pain management. [ABSTRACT FROM AUTHOR]

A comprehensive experimental study on high-velocity oxygen-fuel (HVOF)- sprayed tungsten carbide/cobalt deposits using laser cladding was conducted. Based on the principles of central composite design, a response surface methodology was elaborated. The results show that a higher thermal gradient cannot be easily generated in the cladding, the claddings had completely melted, and the structure is highly dense without microcracks. The brighter white splats indicate unmolten material. The resulting lower residual stress decreases the fracture crack activities and does not easily induce delamination in the laser clads. Experimental data indicate that the predictions of the second-order model are quite accurate, and it is a reliable predictor of the stress for laser-based HVOF coatings. Findings from this study would contribute considerably to optimizing the experiments and achieving an enhanced structural evolution in the protective coating of traditional handicraft products by laser cladding. [ABSTRACT FROM AUTHOR]

Background: CXCL11 has been reported to be up-regulated in hepatocellular carcinoma (HCC) tissues and cancer-associated fibroblasts (CAFs), and CAF-secreted CXCL11 has been found to promote HCC cell proliferation and migration. Knowledge on how CAFs promote HCC progression is imperative for the future design of anti-tumor drugs addressing the high rates of disease recurrence. Herein, we propose a mechanism by which LINC00152 positively regulates CXCL11 expression and, subsequently, HCC cell phenotypes and growth characteristics via miR-205-5p in CAFs. Methods: The expression of LINC00152, miR-205-5p in HCC/non-cancerous tissues, CAFs/NFs and HCC cell lines was determined by RT-qPCR. The CXCL11 expression and secretion were determined by westernblot and ELISA. Different expressions of LINC00152, CXCL11 and miR-205-5p in CAFs were achieved by transfection with corresponding overexpression/knockdown vectors or mimics/inhibitor. The interactions among LINC00152, miR-205-5p and CXCL11 were confirmed by FISH, luciferase, AGO2 and RNA-pulldown assays. Transwell, colony formation and MTT assays were performed to assess the role of CAFs conditioned medium (CM) in HCC cell phenotype. BALB/c nude mice xenografts were used to determine the role of CAFs on HCC growth in vivo. Results: We found that in vitro, CM from CAFs transfected with sh-LINC00152 dramatically suppressed HCC cell viability, colony formation and migration, and that CM from CAFs transfected with miR-205-5p inhibitor (CAF-CM (miR-205-5p inhibitor)) exerted opposite effects on HCC cell phenotypes. Exogenous overexpression of CXCL11 in CAFs or CAF-CM (miR-205-5p inhibitor) could partially attenuate the effects of LINC00152 knockdown. In contrast, CM from CAFs transfected with LINC00152 dramatically increased HCC cell viability, colony formation and migration, and CM from CAFs transfected with miR-205-5p mimics (CAF-CM (miR-205-5p mimics)) exerted opposite effects on HCC cell phenotypes. Knockdown of CXCL11 in CAFs or CAF-CM (miR-205-5p mimics) could partially attenuate the effects of LINC00152 overexpression. In vivo, LINC00152 knockdown in CAFs inhibited tumor growth in a mouse model, which could be reversed by CXCL11 overexpression in CAFs. Mechanistically, we found that LINC00152 could act as a ceRNA to counteract miR-205-5p-mediated suppression on CXCL11 by directly binding to miR-205-5p and the 3'UTR of CXCL11. Conclusion: Our data indicate that a LINC00152/miR-205-5p/CXCL11 axis in HCC CAFs can affect the proliferative and migrative abilities of HCC cells in vitro and HCC tumor growth in vivo. [ABSTRACT FROM AUTHOR]

Skeleton curve-guided five-axis sweep scanning is an emerging surface inspection technique with marvelous inspection efficiency. The precondition of applying such a technique to a complex surface is to extract the skeleton curves of a two-manifold surface associated with partitioning the surface into compact surfaces. However, the work on extracting skeletons of two-manifold triangle mesh surfaces is scarce, as existing skeletonization methods mostly focus on either 2D planar shapes or 3D solid shapes. In this paper, we present a new approach to extract the skeletons on a two-manifold triangle mesh with boundaries. The skeletons are formed in the most intuitive manner of wave front propagation which is based on computing the initial value problem of geodesics on a triangle mesh. The step-length of wave front propagation is adaptively controlled to guarantee the appropriate density of skeleton points for having good connectivity. Experiments show that, as a direct application of the proposed skeleton generation and its associated surface partitioning result, the five-axis sweep scanning path of complex free-form surface can be generated conveniently. Experimental results also validate that the computation of our proposed approach is simpler and faster than the state-of-the-art geodesic Voronoi diagram (GVD) method when most of the two-manifold triangle mesh is nearly planar. Additionally, the augmented parameter used for tracing the wave front's geodesic propagation information is helpful for the skeleton-based surface partition, which is necessary for skeleton curve-guided five-axis sweep scanning. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a leading cause of cancer-related death. There is an urgent need for new methods of early CRC detection and monitoring to improve patient outcomes. Extracellular vesicles (EVs) are secreted, lipid-bilayer bound, nanoparticles that carry biological cargo throughout the body and in turn exhibit cancer-related biomarker potential. RNA binding proteins (RBPs) are posttranscriptional regulators of gene expression that may provide a link between host cell gene expression and EV phenotypes. Insulin-like growth factor 2 RNA binding protein 1 (IGF2BP1/IMP1) is an RBP that is highly expressed in CRC with higher levels of expression correlating with poor prognosis. IMP1 binds and potently regulates tumor-associated transcripts that may impact CRC EV phenotypes. Our objective was to test whether IMP1 expression levels impact EV secretion and/or cargo. We used RNA sequencing, in vitro CRC cell lines, ex vivo colonoid models, and xenograft mice to test the hypothesis that IMP1 influences EV secretion and/or cargo in human CRC. Our data demonstrate that IMP1 modulates the RNA expression of transcripts associated with extracellular vesicle pathway regulation, but it has no effect on EV secretion levels in vitro or in vivo. Rather, IMP1 appears to affect EV regulation by directly entering EVs in a transformation-dependent manner. These findings suggest that IMP1 has the ability to shape EV cargo in human CRC, which could serve as a diagnostic/prognostic circulating tumor biomarker. NEW & NOTEWORTHY This work demonstrates that the RNA binding protein IGF2BP1/IMP1 alters the transcript profile of colorectal cancer cell (CRC) mRNAs from extracellular vesicle (EV) pathways. IMP1 does not alter EV production or secretion in vitro or in vivo, but rather enters CRC cells where it may further impact EV cargo. Our work shows that IM [ABSTRACT FROM AUTHOR]

The article presents a study which discovered that the topology of structures fundamentally dictates the topological properties of optical fields and offers a new dimension to exploit for optical functionalities that are irrelevant to specific material constituents or structural geometries. Topics include polarization singularities (PSs) protected by surface topology of structures, integration of topology and mirrors symmetry, and integration of topology and generalized rotational symmetry.

The combination of docetaxel, cisplatin, and S-1 (DCS) is a common chemotherapy regimen for patients with gastric cancer (GC). However, studies on long noncoding RNAs (lncRNAs) associated with the chemotherapeutic response to and prognosis after DCS remain lacking. The aim of the present study was to identify DCS mRNAs-lncRNAs associated with chemotherapy response and prognosis in GC patients. In the present study, we identified 548 lncRNAs associated with these 16 mRNAs in the TCGA and GSE31811 datasets. Eleven lncRNAs were used to construct a prognostic signature by least absolute shrinkage and selection operator (LASSO) regression. A model including the 11 lncRNAs (LINC02532, AC007277.1, AC005324.4, AL512506.1, AC068790.7, AC022509.2, AC113139.1, LINC00106, AC005165.1, MIR100HG, and UBE2R2-AS1) associated with the prognosis of GC was constructed. The signature was validated in the TCGA database, model comparison, and qRT-PCR experiments. The results showed that the risk signature was a more effective prognostic factor for GC patients. Furthermore, the results showed that this model can well predicting chemotherapy drug response and immune infiltration of GC patients. In addition, our experimental results indicated that lower expression levels of LINC00106 and UBE2R2-AS1 predicted worse drug resistance in AGS/DDP cells. The experimental results agreed with the predictions. Furthermore, knockdown of LINC00106 or UBE2R2-AS1 can significantly enhanced the proliferation and migration of GC AGS cells in vitro. In conclusion, a novel DCS therapy-related lncRNA signature may become a new strategy to predict chemotherapy response and prognosis in GC patients. LINC00106 and UBE2R2-AS1 may exhibit a tumor suppressive function in GC. [ABSTRACT FROM AUTHOR]

This paper proposes a deep learning-based generalized empirical flow model (EFM) that can provide a fast and accurate prediction of the glottal flow during normal phonation. The approach is based on the assumption that the vibration of the vocal folds can be represented by a universal kinematics equation (UKE), which is used to generate a glottal shape library. For each shape in the library, the ground truth values of the flow rate and pressure distribution are obtained from the high-fidelity Navier–Stokes (N–S) solution. A fully connected deep neural network (DNN) is then trained to build the empirical mapping between the shapes and the flow rate and pressure distributions. The obtained DNN-based EFM is coupled with a finite element method (FEM)-based solid dynamics solver for fluid–structure–interaction (FSI) simulation of phonation. The EFM is evaluated by comparing the N-S solutions in both static glottal shapes and FSI simulations. The results demonstrate a good prediction performance in accuracy and efficiency. [ABSTRACT FROM AUTHOR]

The article presents a study on glucose-6-phosphate dehydrogenase (G6PD) -mediated increase in de novo NADP+ biosynthesis which promotes antioxidant defense and tumor metastasis. The article discusses various topics including expansion of nicotinamide adenine dinucleotide phosphate (NADPH) and NADP+ pools under oxidative stress conditions, nicotinamide adenine dinucleotide kinase (NADK1) is important for NADP(H) pool expansion, and the ability of G6PD in stimulating de novo NADP+ synthesis.

In this paper, the temperature rise in the longitudinal direction, the heat release rate (HRR), the endless area temperature under the ceiling of the utility tunnel, and the root of HRR (oil and fuel type), cable type, number of cable layers and and cables per layer. The effects of airtightness, natural ventilation, and longitudinal ventilation on the fire characteristics of cable compartments were compared. The results showed that the effects of enclosed cable tunnels and natural ventilation on fire behavior near walls in cable tunnels were compared. Compared with the natural ventilation state, when placing RVVR type cables, the fire duration of the enclosed cable compartment was shorter, the ceiling temperature rise was greater. And the time that was necessary to increase the ceiling temperature to its maximum value was shorter. The HRR inside the enclosed cable compartment was very high and could almost reach its peak quickly. The contribution of this article is to reduce the social and economic costs of utility tunnels by preventing tunnel fires. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota is crucial in the process of radiation enteritis (RE). Asrecommended by Chinese expert consensus, three formulas such as Baitouweng decoction, Gegen Qinlian decoction, and Shaoyao decoction, are used to prevent the same type of RE. Methods: Herein, we aimed to investigate the common pharmaceutical ingredients andmolecular mechanisms of the three formulas on RE from the perspective of gut microbiotathrough multi-bioinformatics analysis and mouse experiment. Results: Interestingly, theimportant active ingredient screened was quercetin in all three herbal formulas, andthedominant targets that participated in RE treatment by targeting gut microbiota regulationwere IL10, STAT1, IL1B, and IL1A. The concentration of quercetin was measured inGegenQinlian decoction > Shaoyao decoction > Baitouweng decoction (P <0.001) usinghighperformance liquid chromatography. Moreover, a total of 40 SPF C57/BL6J (male, 12–14weeks old) mice were assigned to perform the validation experiment with various quercetinintervention doses. Quercetin significantly protected against inflammatory responseinradiation induced-mice. The microbial alterations in the gut caused by quercetinintervention in radiation-induced mice were also explained. We further confirmedthealterations in the relative mRNA expression of the three formulas for the treatment of RE, which have four similar gut microbiota-regulated targets (IL10, STAT1, IL1B, andIL1A). Conclusion: These findings show that quercetin regulated the gut microbiota for REtherapy, a connotation that works on the principle of “different treatments for the samedisease” for RE. The present investigation provides methodological guidelines and protocolsfor the modern use and examination of traditional therapeutic concepts. [ABSTRACT FROM AUTHOR]

TMEMI6F, a Ca2+-activated phospholipid scramblase (CaPLSase), is critical for placental trophoblast syncytialization, HIV infection, and SARS-CoV2-mediated syncytialization, however, how TMEM16F is activated during cell fusion is unclear. Here, using trophoblasts as a model for cell fusion, we demonstrate that Ca2+ influx through the Ca2+ permeable transient receptor potential vanilloid channel TRPV4 is critical for TMEM16F activation and plays a role in subsequent human trophoblast fusion. GSK1016790A, a TRPV4 specific agonist, robustly activates TMEM16F in trophoblasts. We also show that TRPV4 and TMEM16F are functionally coupled within Ca2+ microdomains in a human trophoblast cell line using patch-clamp electrophysiology. Pharmacological inhibition or gene silencing of TRPV4 hinders TMEM16F activation and subsequent trophoblast syncytialization. Our study uncovers the functional expression of TRPV4 and one of the physiological activation mechanisms of TMEM16F in human trophoblasts, thus providing us with novel strategies to regulate CaPLSase activity as a critical checkpoint of physiologically and disease-relevant cell fusion events. [ABSTRACT FROM AUTHOR]

Topological insulators that can host special symmetry-protected boundary states and corner states have attracted increasing intention in acoustic engineering. Recently, the concept of the boundary-obstructed topological (BOT) phases has defined a class of topological phases without bulk energy band closing around zero energy, which greatly broadens the applications of the topological states. In this work, based on the two-dimensional Su–Schrieffer–Heeger network, we show that the band degeneracies around zero energy can be removed to open a complete bandgap by judiciously tuning the hopping terms to break C 4 v symmetry down to C 2 v symmetry but with the topological phase invariant, which can be directly characterized by the BOT phase. Furthermore, we experimentally propose a rigorous acoustic sample to visualize the hierarchy of the in-gap higher-order topological states exactly. Crucially, by designedly connecting the lattice with outside environment, we show that these spectrally isolated states still response to the specific frequencies robustly. Our results are expected to be helpful for manipulating wave propagation and sound energy harvesting. [ABSTRACT FROM AUTHOR]

Introduction: Vascular cognitive impairment (VCI) and Alzheimer's disease are the most common cognitive impairment diseases in the elderly. This study aimed to apply the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) scale to evaluate VCI in elderly patients and analyze its reliability and validity. Methods: We enrolled 278 VCI patients admitted to our hospital, from June 2017 to June 2018. The basic clinical information of each patient was documented, and the Mini-Mental State Examination (MMSE) and the RBANS scales were suggested to complete. Results: We found significant correlations between the RBANS total score and age, diabetes, hypertension, coronary heart disease and years of education. The internal consistency of the RBANS scale Cronbach α suggested a good agreement with the total score and the single score at two time points. Moreover, the RBANS total score and the score of each dimension in the RBANS scale were positively correlated with the MMSE immediate memory, calculation ability, delayed memory, commanding ability, reading comprehension ability, command execution, sentence making, and pattern duplicating ability. Conclusion: In conclusion, the RBANS has good reliability and validity for the assessment of cognitive dysfunction in elderly VCI patients. It can be used as a routine clinical and research tool, for the simplicity in operation and superior acceptance. [ABSTRACT FROM AUTHOR]

Mathematics plays a leading part in day-to-day life and has enhanced a necessary component for human accomplishments. Students from many countries do not reach the expected level in mathematics. Therefore, it is essential to pay close consideration to the causes related to ability in mathematics. Mathematics attitude is considered as one of the critical variables in the process of mathematics learning. This study aimed to determine students' attitudes and achievements through problem-based learning in mathematics. The selected study group contained 600 students and 35 teachers from rural public secondary schools in District Rawalpindi, Pakistan. The data collection was done using questionnaires from students and teachers and collected data analyzed by SPSS 23 and Amos 23. This study's result was carried out using Partial Least square structural equation Model (PLS-SEM), descriptive analysis, and hypotheses testing. The outcomes in this study indicated that the mean fluctuated between 1 to 4.5, 3.71 to 4.20, and Std. Deviation fluctuated between 0.6 to 2.0 and 0.75 to 1.55 in the students and teacher models, respectively. The results of the PLS-SEM students' model show a negative attitude towards mathematics. The teachers' PLS-SEM model showed the Effects of using problem-based learning (PBL) on students' achievements. According to the hypotheses testing, the acceptance of hypotheses by stating that the Confidence in Learning Mathematics Scale (C), Value of Mathematics Scale (V), and Student Mathematics Motivation Scale (M) are significant effects for the Students' Attitude Toward Problem-Based Learning (ATPBL). But the Attitude Toward Enjoyment in Mathematics Scale (AE) was rejected, and it did not significantly affect the ATPBL. As well as, the Problem-solving learning and students' achievement (PLA), Advantages of problem-solving learning (APL) and Difficulties in using problem-solving learning (DPL) have a significant positive effect on the ATPBL. Finally, this study suggested that teachers also adopt new teaching methods corresponding to mathematics, and there is a need to explore particular mathematics skills to enhance students' learning abilities. [ABSTRACT FROM AUTHOR]

Thermal deviation induced by ambient temperature changes and heat generated during machine operations influences the accuracy of machine tools. A thermal test is essential to evaluate the influence of thermal deviation. ISO 230-3 provides displacement sensor-based thermal tests for machine tools. This paper proposes a machining test that enables a user to visually, by the naked eye, observe the integrated thermal influence on the tool trajectory's displacement in the direction normal to the test piece surface from the length of the machined slots. The proposed test consists of the machining of the five surfaces to observe the thermal influence of the tool position with respect to the test piece in X, Y, and Z directions, as well as the position of two rotary axes with respect to the tool position. The advantages of the proposed test include that it requires no measuring instrument to quantitatively evaluate the thermal error in all directions. And since the thermal influence is evaluated by observing the position where the cutting tool leaves the test piece surface, where the cutting force is zero, the influence of the cutting force on the test results can be ignored. Thermal influences of a five-axis machine tool during the warm-up cycle are investigated by experiment to validate the feasibility of the proposed method. Results show that 150 min is needed for sufficient warm-up for the selected machine tool if permissible tolerance for thermal deviation is 2.5 µm for all the errors. [ABSTRACT FROM AUTHOR]

A growing number of gain-of-function (GOF) BK channelopathies have been identified in patients with epilepsy and movement disorders. Nevertheless, the underlying pathophysiology and corresponding therapeutics remain obscure. Here, we utilized a knockin mouse model carrying human BK-D434G channelopathy to investigate the neuronal mechanism of BK GOF in the pathogenesis of epilepsy and dyskinesia. The BK-D434G mice manifest the clinical features of absence epilepsy and exhibit severe motor deficits and dyskinesia-like behaviors. The cortical pyramidal neurons and cerebellar Purkinje cells from the BK-D434G mice show hyperexcitability, which likely contributes to the pathogenesis of absence seizures and paroxysmal dyskinesia. A BK channel blocker, paxilline, potently suppresses BK-D434G–induced hyperexcitability and effectively mitigates absence seizures and locomotor deficits in mice. Our study thus uncovered a neuronal mechanism of BK GOF in absence epilepsy and dyskinesia. Our findings also suggest that BK inhibition is a promising therapeutic strategy for mitigating BK GOF-induced neurological disorders. [ABSTRACT FROM AUTHOR]

The parity-time (PT)-symmetric system has been a hot research topic in recent years. Nevertheless, the corresponding gain part is hard to be realized experimentally in acoustic systems. In this paper, by combining the concept of injecting external energy and the soundwave–structure interaction, we propose a S-shaped waveguide model with a wave modulator, which exactly obtains the effective acoustic gain medium. We both numerically and experimentally show the implementation of the acoustic gain medium and calculate the effective parameter refractive index by the standard retrieval method. Crucially, the flexible reconstructions of the proposed structure can be easily conducted by merely changing one parameter of the proposed structure (e.g., height of the wave modulator). Moreover, to construct the on-demand PT-symmetric refractive index period, we further present a practical approach by applying the well-selected parameters of the model and analyzing the modulator's impedance. Our results are expected to be helpful for the design and potential applications of the acoustic PT-symmetric systems. [ABSTRACT FROM AUTHOR]

Due to the potential engineering needs, the passive tunable metasurfaces with a high performance equivalent to the active phased array is worthy of research. Here, a passive ultrathin metasurface unit composed of a piezoelectric composite structure (PCS) connected to an external capacitor, which can modulate the phase of the transmitted acoustic waves at a deep subwavelength scale only by controlling the external capacitor but without changing the structure, is proposed. Then, a tunable acoustic metasurface composed of 20 identical PCSs is introduced to realize three acoustic functions, beam steering, beam focusing, and tweezer-like beam generating, just by changing the external capacitors. The phase-control abilities of the PCS unit and three functions of the designed metasurface are proved both numerically and experimentally. This study provides the possibility to design ultrathin tunable acoustic metasurfaces with the ability of precise control and passive materials. [ABSTRACT FROM AUTHOR]

Background: Oncogenic KRAS mutations are prevalent in human cancers, but effective treatment of KRAS-mutant malignancies remains a major challenge in the clinic. Increasing evidence suggests that aberrant metabolism plays a central role in KRAS-driven oncogenic transformation. The aim of this study is to identify selective metabolic dependency induced by mutant KRAS and to exploit it for the treatment of the disease. Method: We performed an integrated analysis of RNAi- and CRISPR-based functional genomic datasets (n = 5) to identify novel genes selectively required for KRAS-mutant cancer. We further screened a customized library of chemical inhibitors for candidates that are synthetic lethal with NOP56 depletion. Functional studies were carried out by genetic knockdown using siRNAs and shRNAs, knockout using CRISPR/Cas9, and/or pharmacological inhibition, followed by cell viability and apoptotic assays. Protein expression was determined by Western blot. Metabolic ROS was measured by flow cytometry-based quantification. Results: We demonstrated that nucleolar protein 5A (NOP56), a core component of small nucleolar ribonucleoprotein complexes (snoRNPs) with an essential role in ribosome biogenesis, confers a metabolic dependency by regulating ROS homeostasis in KRAS-mutant lung cancer cells and that NOP56 depletion causes synthetic lethal susceptibility to inhibition of mTOR. Mechanistically, cancer cells with reduced NOP56 are subjected to higher levels of ROS and rely on mTOR signaling to balance oxidative stress and survive. We also discovered that IRE1α-mediated unfolded protein response (UPR) regulates this process by activating mTOR through p38 MAPK. Consequently, co-targeting of NOP56 and mTOR profoundly enhances KRAS-mutant tumor cell death in vitro and in vivo. Conclusions: Our findings reveal a previously unrecognized mechanism in which NOP56 and mTOR cooperate to play a homeostatic role in the response to oxidative stress and suggest a new rationale for the treatment of KRAS-mutant cancers. [ABSTRACT FROM AUTHOR]

This article explores the political behavior of private entrepreneur delegates (PEDs) in the Chinese People's Political Consultative Conference (CPPCC). Drawing evidence from a data set consisting of personal background and behavioral information for 2295 members of the 11th CPPCC (2008-12), we probe into the behavioral patterns of 178 PEDs in the proposal process. Our findings reveal that PEDs' participation demonstrates more economic rather than political aspirations, which suggests that a major motivation of their participation is enhancing economic well-being rather than initiating political changes. Party affiliation is associated with the PEDs' engagement in the proposal process, possibly through two mechanisms. In the preselection mechanism, PEDs' with different political ideologies and preferences tend to be assimilated into different party backgrounds before becoming a delegate, hence different participation patterns. In the resource mobilization mechanism, party backgrounds may influence their capacity to effectively participate in the proposal process due to the resources provided by their party organizations. [ABSTRACT FROM AUTHOR]

Although the self-consistency of the full matrix material constants of a piezoelectric sample obtained by the resonant ultrasonic spectroscopy technique can be guaranteed because all constants come from the same sample, it is a great challenge to determine the constants of a piezoelectric sample with strong anisotropy because it might not be possible to identify enough resonance modes from the resonance spectrum. To overcome this difficulty, we developed a strategy to use two samples of similar geometries to increase the number of easy identifiable modes. Unlike the IEEE resonance methods, sample-to-sample variation here is negligible because the two samples have almost the same dimensions, cut from the same specimen and poled under the same conditions. Using this method, we have measured the full matrix constants of a [011]c poled 0.71Pb(Mg1/3Nb2/3)O3-0.29PbTiO3 single crystal, which has 17 independent constants. The self-consistency of the obtained results is checked by comparing the calculated elastic stiffness constants cD33, cD44, and cD55 with those directly measured ones using the ultrasonic pulse-echo method. [ABSTRACT FROM AUTHOR]

Humans have an extraordinary ability to recognize and differentiate voices. It is yet unclear whether voices are uniquely processed in the human brain. To explore the underlying neural mechanisms of voice processing, we recorded electrocorticographic signals from intracranial electrodes in epilepsy patients while they listened to six different categories of voice and nonvoice sounds. Subregions in the temporal lobe exhibited preferences for distinct voice stimuli, which were defined as "voice patches." Latency analyses suggested a dual hierarchical organization of the voice patches. We also found that voice patches were functionally connected under both task-engaged and resting states. Furthermore, the left motor areas were coactivated and correlated with the temporal voice patches during the sound-listening task. Taken together, this work reveals hierarchical cortical networks in the human brain for processing human voices. [ABSTRACT FROM AUTHOR]

In this study, the added resistance and seakeeping performance of the KVLCC2 ship is investigated by using the spectral wave explicit Navier-Stokes equations (SWENSE) method. The SWENSE method is based on the decomposition of the total field into an incident part explicitly obtained by the wave potential flow theory and a complementary part solved with a modified Reynolds-averaged Navier-Stokes solver. Therefore, the computational efficiency can be achieved by using a relatively coarse mesh in the far field, retaining the accuracy of the incident waves. A parametric study is performed under regular wave conditions with 3Degree of Freedom (DOF) motions of the hull. The results are compared with the large literature available. An additional case is simulated to demonstrate the capability of the present method in simulating seakeeping problems in irregular sea states. Good agreement between the computed results with the reference data can be observed for the hull model, which indicates that the added resistance and seakeeping performances can be well predicted by the present method. [ABSTRACT FROM AUTHOR]

The slat of a high-lift wing can be a significant noise source during approach and landing. This paper describes an experimental study of the effects of two passive devices (namely, slat extensions and a cove filler) on the aerodynamics and acoustic radiation from a 30P30N model. Test conditions include three effective free-air angles of attack of 5.5, 7.5, and 13 deg, as well as three Reynolds numbers of 1.2, 1.5, and 1.71×106. Steady surface pressure measurements are used to assess the aerodynamics near the midspan section. Unsteady surface pressure and far-field acoustic array measurements are performed to evaluate the near- and far-field pressure fluctuations, respectively. Delay-and-sum beamforming is applied to localize the noise sources and to provide integrated spectra. The slat cusp extensions barely affect the mean Cp distribution, whereas the longest extension achieves up to a 5.4 dB reduction in the overall sound pressure level. The slat-cove filler yields an even higher noise reduction that is lower than the baseline by up to 14 dB. Even though the aerodynamic assessment of the cove filler is incomplete due to the covered pressure ports, the mean Cp distribution over the remaining surface of the model indicates a rather small change compared with the baseline measurements. [ABSTRACT FROM AUTHOR]