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Abnormal growth of airway smooth muscle cells is one of the key features in asthmatic airway remodeling, which is associated with asthma severity. The mechanisms underlying inappropriate airway smooth muscle cell growth in asthma remain largely unknown. Myocd has been reported to act as a key transcriptional coactivator in promoting airway-specific smooth muscle development in fetal lungs. Whether Myocd controls airway smooth muscle remodeling in asthma has not been investigated. Mice with lung mesenchyme-specific deletion of Myocd after lung development were generated, and a chronic asthma model was established by sensitizing and challenging the mice with ovalbumin for a prolonged period. Comparison of the asthmatic pathology between the Myocd knockout mice and the wild-type controls revealed that abrogation of Myocd mitigated airway smooth muscle cell hypertrophy and hyperplasia, accompanied by reduced peri-airway inflammation, decreased fibrillar collagen deposition on airway walls, and attenuation of abnormal mucin production in airway epithelial cells. Our study indicates that Myocd is a key transcriptional coactivator involved in asthma airway remodeling. Inhibition of Myocd in asthmatic airways may be an effective approach to breaking the vicious cycle of asthmatic progression, providing a novel strategy in treating severe and persistent asthma. © 2022 The Authors. The Journal of Pathology published by John WileySons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The BeB12+ cluster adopts tubular structure, featuring three-fold π/σ aromaticity. Once sequential reduction, the structural transformation occurs from tubular shape to planar. The planar BeB12− is governed by 7π/10σ delocalization.

La©B8C4+/0/− clusters adopt interesting molecular wheel structures with a dodeca-coordinated La in plane, setting a record for planar structures in chemistry. We provide new ideas and concepts for searching for planar hyper-coordinated systems.

Based on neural networks, coarse-grained glucose–water dissolution pair models with all-atomic system precision are developed, which can be used to explore the dynamics of dissolutive wetting on larger scales.

We propose an intramolecular synergistic counteracting strategy of fluorescence resonance energy transfer and the inner filter effect for accurate photoactivation monitoring, to eliminate the influence of the biological microenvironment.

Fretting wear has an adverse impact on the fatigue life of turbine blade roots. The current work is to comparatively investigate the fretting wear behaviour of the nickel-based superalloy surfaces produced by polishing and creep-feed profile grinding, respectively, in terms of surface/subsurface fretting damage, the friction coefficient, wear volume and wear rate. Experimental results show that the granulated tribolayer aggravates the workpiece wear, while the flat compacted tribolayer enhances the wear resistance ability of workpiece, irrespective of whether the workpiece is processed by polishing or grinding. However, the wear behaviors of tribolayers are different. For the polished surface, when the normal load exceeds 100 N, the main defects are crack, rupture, delamination and peeling of workpiece materials; the wear mechanism changes from severe oxidative wear to fatigue wear and abrasive wear when the loads increase from 50 to 180 N. As for the ground surface, the main wear mechanism is abrasive wear. Particularly, the ground surface possesses better wear-resistant ability than the polished surface because the former has the lower values in coefficient friction (0.23), wear volume (0.06×106 μm3) and wear rate (0.25×10-16 Pa-1). Finally, an illustration is given to characterize the evolution of wear debris on such nickel-based superalloy on the ground surface.

This paper is concerned with the existence of solutions for p -Laplace problems with non-local term. We prove the sub-supersolution theorem using the pseudomonotone operator theorem and Minty–Browder theorem with appropriate assumptions on M , g i i = 1,2 . Then, using the sub-supersolution approach, we determine the existence of positive solutions to specific problems.

A study on ultrasonic vibration-assisted electrical discharge machining (UVEDM) micro-hole, which mainly includes three key designs, was conducted to improve the machining performance of the electric discharge machining (EDM) micro-holes on TC4 titanium alloy. First, a mathematical model for the velocity of the flow field in the interelectrode gap was established. Consequently, the effect of the presence or absence of ultrasonic vibration on the flow velocity was analyzed. Furthermore, based on COMSOL Multiphysics, the two distributions of the flow field and the debris in the interelectrode gap were simulated and the influence of ultrasonic amplitude on them was analyzed. Finally, the study of UVEDM micro-hole machining with different ultrasonic amplitudes was conducted. The machining performance of the UVEDM micro-hole was found to increase with the increment of the ultrasonic amplitude and the optimal value of 5.22 µm, while the performance decreases when the ultrasonic amplitude goes beyond the optimal value. Compared with EDM micro-hole, the MMR is increased by 2.4 times, and the electrode loss and hole taper are reduced by 56% and 24%, respectively.

Introduction Hypoxia-inducible factor (HIF)1α has been shown to be activated and induces a glycolytic shift under hypoxic condition, however, little attention was paid to the role of HIF1α-actuated fructolysis in hypoxia-induced heart injury. Objectives In this study, we aim to explore the molecular mechanisms of miR-155-mediated fructose metabolism in hypoxic cardiac fibroblasts (CFs). Methods Immunostaining, western blot and quantitative real-time reverse transcription PCR (qRT-PCR) were performed to detect the expression of glucose transporter 5 (GLUT5), ketohexokinase (KHK)-A and KHK-C in miR-155−/− and miR-155wt CFs under normoxia or hypoxia. A microarray analysis of circRNAs was performed to identify circHIF1α. Then CoIP, RIP and mass spectrometry analysis were performed and identified SKIV2L2 (MTR4) and transformer 2 alpha (TRA2A), a member of the transformer 2 homolog family. pAd-SKIV2L2 was administrated after coronary artery ligation to investigate whether SKIV2L2 can provide a protective effect on the infarcted heart. Results When both miR-155−/− and miR-155wt CFs were exposed to hypoxia for 24 h, these two cells exhibited an increased glycolysis and decreased glycogen synthesis, and the expression of KHK-A and KHK-C, the central fructose-metabolizing enzyme, was upregulated. Mechanistically, miR-155 deletion in CFs enhanced SKIV2L2 expression and its interaction with TRA2A, which suppresses the alternative splicing of HIF1α pre-mRNA to form circHIF1α, and then decreased circHIF1α contributed to the activation of fructose metabolism through increasing the production of the KHK-C isoform. Finally, exogenous delivery of SKIV2L2 reduced myocardial damage in the infarcted heart. Conclusion In this study, we demonstrated that miR-155 deletion facilitates the activation of fructose metabolism in hypoxic CFs through regulating alternative splicing of HIF1α pre-mRNA and thus circHIF1ɑ formation.

Background. Cough variant asthma (CVA) has no definitive diagnosis or pathogenic causes, and there is currently no effective and safe treatment. Methods. The network pharmacology was employed to investigate possible targets of Zhisou San (ZSS) in CVA treatment. The main chemical constituents of seven herbs in ZSS were collected based on the TCMSP. To explain the main mechanism, we sequentially screened the targets of each active ingredient and constructed the network of “herb-ingredient-target-disease.” The core targets of ZSS were further confirmed by the molecular docking analysis. Furthermore, pulmonary function, histopathology, and biochemical assays in mice were used to investigate the effect of ZSS on the treatment of CVA. Results. A total of 137 active ingredients and 86 potential targets for the ZSS in the treatment of CVA were screened, which were connected with the regulation of inflammatory response and immune balance, such as IL-17 signaling pathway, Th17 cell differentiation, TNF signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway, T-cell receptor signaling pathway, Th1 and Th2 cell differentiation, and other signaling pathways closely related to the pathogenesis of CVA. Thereinto, 29 core targets contained 8 of the highest scores and could evidently bind to components such as stigmasterol, quercetin, stemoninine B, luteolin, and β-sitosterol predicted by molecular docking. Furthermore, experiments in vivo were conducted for further validation that ZSS had essential effects on lung function and histopathology as well as the inflammatory state in CVA mice, which was significantly related to regulating the Th17/Treg immune balance to reduce inflammation as the important pharmacological mechanism. Conclusion. This study revealed that ZSS has multicomponent and multipathway characteristics of ZSS in the treatment of CVA, which was primarily associated with inflammation and Th17/Treg immune balance. This study provides a scientific foundation for systematically elaborating the pharmacological activities and mechanism of ZSS, as well as explaining the reliability of the TCM compatibility theory.

Aims: To explore the characteristics of diabetic lung injury and the role of resistin-like molecule β (RELMβ). Methods: The experimental diabetic mice were established by intraperitoneal injection of streptozotocin (STZ), the lung function, tissue structure and protein expression levels of the mice were observed. The role of RELMβ on the epithelial to mesenchymal transition (EMT) in A549 cells exposed to high glucose was explored. Results: The function and structure of the diabetic lungs were significantly impaired, with extensive collagen fibers and macrophages deposited in the alveolar septum, with declined expression of epithelial marker (E-cadherin) and increased expression of mesenchymal markers (α-SMA and Vimentin) and RELMβ. The expression and secretion of RELMβ in macrophages were stimulated by high glucose, and the EMT level in A549 cells was up-regulated by recombinant human RELMβ or co-culture with macrophages. Conclusions: Diabetic mice showed declined lung function and increased fibrotic changes in lung tissues. Macrophages exposed to high glucose can promote the EMT progression in A549 cells via secreting RELMβ.

Surface enhanced Raman scattering (SERS) is a rapid and nondestructive technique that is capable of detecting and identifying chemical or biological compounds. Sensitive SERS quantification is vital for practical applications, particularly for portable detection of biomolecules such as amino acids and nucleotides. However, few approaches can achieve sensitive and quantitative Raman detection of these most fundamental components in biology. Herein, a noble-metal-free single-atom site on a chip strategy was applied to modify single tungsten atom oxide on a lead halide perovskite, which provides sensitive SERS quantification for various analytes, including rhodamine, tyrosine and cytosine. The single-atom site on a chip can enable quantitative linear SERS responses of rhodamine (10Supplementary material is available for this article at 10.1007/s40843-022-1968-5 and is accessible for authorized users.表面增强拉曼散射(SERS)是一种快速且无损的化学和生物分子检测技术. 高灵敏且定量化的SERS检测技术对其在实际中的应用至关重要, 尤其是对生物分子如氨基酸和碱基的便携化检测. 但是鲜有技术手段能够实现对这些最基本的生物分子进行高灵敏且定量化的拉曼检测. 我们提出了一种无需贵金属的单原子位点修饰芯片策略, 用钨单原子氧化物修饰铅卤钙钛矿芯片, 实现了多种检测物的高灵敏定量化识别, 包括罗丹明、 酪氨酸和胞嘧啶. 芯片上单原子位点技术能够实现对罗丹明、 酪氨酸和胞嘧啶的线性检测, 相应的定量化区间分别为: 10

The outbreak of the global COVID-19 pandemic has become a public crisis and is threatening human life in every country. Recently, researchers have developed testing methods via patients cough recordings. In order to improve the testing accuracy, in this paper, we establish a novel COVID-19 sound-based diagnosis framework, i.e. TFA-CLSTMNN, which integrates time-frequency domain features of the recorded cough with the Attention-Convolution Long Short-Term Memory Neural Network. Specifically, we calculate the Mel-frequency cepstrum coefficient (MFCC) of the cough data to extract the time-frequency domain features. We then apply the convolutional neural network and the attentional mechanism on the time-frequency features, which is followed by the long short-term memory neural network to analyze the MFCC features of the data. The recognition and classification can be then carried out to evaluate the positiveness or negativeness of the tested samples. Experimental results show that the proposed TFA-CLSTMNN framework outperforms the baseline neural networks in sound-based COVID-19 diagnosis and derives an accuracy over 0.95 on the public real-world datasets.

Migratory divides are contact zones between breeding populations with divergent migratory strategies during the nonbreeding season. These locations provide an opportunity to evaluate the role of seasonal migration in the maintenance of reproductive isolation, particularly the relationship between population structure and features associated with distinct migratory strategies. We combine light-level geolocators, genomic sequencing, and stable isotopes to investigate the timing of migration and migratory routes of individuals breeding on either side of a migratory divide coinciding with genomic differentiation across a hybrid zone between barn swallow (Hirundo rustica) subspecies in China. Individuals west of the hybrid zone, with H. r. rustica ancestry, had comparatively enriched stable-carbon and hydrogen isotope values and overwintered in eastern Africa, whereas birds east of the hybrid zone, with H. r. gutturalis ancestry, had depleted isotope values and migrated to southern India. The two subspecies took divergent migratory routes around the high-altitude Karakoram Range and arrived on the breeding grounds over 3 weeks apart. These results indicate that assortative mating by timing of arrival and/or selection against hybrids with intermediate migratory traits may maintain reproductive isolation between the subspecies, and that inhospitable geographic features may have contributed to the diversification of Asian avifauna by influencing migratory patterns.

Aims: In order to understand the role of allelopathy in invasion success, effects of root exudates from Solanum rostratum Dunal on germination and primary growth of wheat and cabbage seeds were studied by vitro bioassay. These results indicated the allelopathy of root exudates and would be helpful for understanding Solanum rostratum Dunal invasion. Study Design: The roots were washed clean for three times with distilled water before they were gathered in a big bucket. The container was filled with distilled water, enough to submerge the roots, and air was aerated constantly with an air pump. The water extract was collected per 24 hs and for four times totally. The water extract from Solanum rostratum was concentrated with a rotary evaporator at 40°C and deposited in a refrigerator at 4°C. All the root exudates were pooled around 1500 mL, and the fresh weight of Solanum rostratum used for exudates collection was 1208 g, the exudate concentration was then marked as 0.8g f w/mL. Place and Duration of Study: Solanum rostratum was grown in the greenhouse on April 15th, 2019, its seeds were collected from the invaded fields in Chaoyang city (Liaoning province, China). Methodology: Petri dish bioassay was applied to test the effects of root exudates of Solanum rostratum on the seeds of wheat and Chinese cabbage. For test of allelochemicals exudated through the root, The compounds in organic fraction of root exudates analysed by GC-MS. Results: These results indicated the allelopathy of root exudates and would be helpful for understanding Solanum rostratum Dunal invasion. Conclusion: Root exudates of Solanum rostratum contained some allelochemicals, which could inhibit the germination and radicle growth of wheat and Chinese cabbage, though the effects of root exudates on shoot growth are different, with a stimulation on Chinese cabbage while a inhibition on wheat. The difference indicated a selectivity of allelopathy effect of root exudates from Solanum rostratum Dunal.

An anti-oil-fouling superhydrophilic composite aerogel (ASG) with a rough surface and macroporous structure is prepared for the solar desalination of oil-in-water emulsion and saline alkali water.

The masterpiece of planar dodeca-coordination has been achieved in the Y©B8C4 cluster, which sets a record coordination number for a planar structure in chemistry.

The fascinating sandwich K6Be2B6H6 cluster with a real borozene ring, being stabilized collectively by three-fold 2σ/6π/2σ aromaticity.

Glioma is one of the leading causes of tumor-related deaths worldwide, but its potential mechanism remains unclear. This study aimed to explore the biological role and potential mechanism of argininosuccinate synthase 1 (ASS1) in glioma. The relative expression levels of ASS1 in glioma specimens and cell lines were calculated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. The biological functions of ASS1 were demonstrated using the 5-ethynyl-2ʹ-deoxyuridine (EdU) assay, transwell assay, and in vivo experiments. In addition, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanism of ASS1 in glioma. ASS1 expression levels were found to be downregulated in glioma specimens and cell lines. Functionally, we confirmed that ASS1 inhibited glioma cell proliferation, migration, invasion, and growth both. Furthermore, we found that ASS1 was a target of N(6)-adenosine-methyltransferase-14 (METTL14)-mediated N6-methyladenosine (m6A) modification. Overexpression of METTL14 markedly elevated ASS1 mRNA m6A modification and suppressed ASS1 mRNA expression. We also revealed that METTL14-mediated ASS1 mRNA degradation relied on the YTH m6A RNA-binding protein 2 (YTHDF2)-dependent pathway. We confirmed that decreased ASS1 expression promoted the cell proliferation, migration, and invasion in glioma, and that the METTL14/ASS1/YTHDF2 regulatory axis may be an effective therapeutic target for glioma.

Based on the basic theory and critical point theory of variable exponential Lebesgue Sobolev space, this paper investigates the existence and multiplicity of solutions for a class of nonlocal elliptic equations with Navier boundary value conditions when (AR) condition does not hold and improves or generalizes the original conclusions.

The ω-phase precipitates in β-Ti alloys increase the strength but significantly degrade the ductility of the alloys. In the present work, the mechanism of ω-strengthening and embrittlement is investigated by using a first principles method based on density functional theory. The generalized stacking fault energies of various slip systems in both the β and ω phases are calculated. The strengthening and embrittlement effects of the ω phase are discussed by comparing the slip energy barriers of slip systems in the β and ω phases with different orientation relationships. It is found that the slip energy barriers of slip systems in the ω phase, except for $$(\bar 2020){[0001]_\omega },$$ are much higher than those of slip systems in the β phase, which explains the ω-strengthening and embrittlement effects. The slip energy barrier of the most active slip system in the phase, $$(\bar 2020){[0001]_\omega },$$ increases with the depletion of Mo and increasing extent of structure collapse, suggesting that aging treatment enhances the -strengthening and embrittlement effects.