Search

Iron isotope compositions, along with the partial extraction of iron in its various forms, can be utilized to investigate the complex interplay of iron migration and transformation with respect to iron isotope patterns. This study investigated the iron composition of a typical loess-paleosol sequence in Northeast China and aimed to understand the influence of iron migration and transformation of the typical loess-paleosol sequence on iron isotopes and environmental and climatic changes that occurred in the region over time by analyzing the distribution and characteristics of iron compositions in sedimentary layers. Samples were collected from Chaoyang in Northeast China, and the iron isotopic composition was analyzed using the multi-receiver inductively coupled plasma mass spectrometer (MC-ICP-MS). The findings revealed depth-dependent variations in the content of different iron forms, reflecting paleoclimatic shifts primarily through pedogenic transformation processes. Notably, iron migration within the section was observed to be limited. The variations in the reddening index and magnetic susceptibility of the loess-paleosol were primarily influenced by the presence of free iron (Fed), exhibiting a range of colors from yellow to red-yellow and red. The δ56Fe values for loess and paleosols ranged from 0.097 ± 0.035‰ to 0.167 ± 0.010‰, with an average of 0.133 ± 0.024‰ and a coefficient of variation (CV) of 15.66% at the stratum scale. These values indicated a systematic enrichment of heavy iron isotopes and a significant negative correlation with the slightly fluctuating total iron content. Specifically, our analysis highlighted distinct differences in δ56Fe values between paleosol (0.126 ± 0.024‰) and loess (0.146 ± 0.021‰). The δ56Fe in Fed was negative, averaging −0.101 ± 0.022‰, while the δ56Fe in silicate-bound iron was positive, averaging 0.156 ± 0.032‰. Intense pedogenesis, driven by warm and wet climates, facilitated iron transformations and migrations, resulting in the accumulation of light iron isotopes in the paleosols. These transformations and migrations were predominantly observed in microdomains characterized by iron depletions and concentrations, as reflected in the profile morphologies. However, the limited iron transformations and migrations did not result in significant Fe redistribution within the soil section, as evidenced by the limited variations in δ56Fe with soil depth at the stratum scale. Sampling from the stratum or pedogenic horizon could potentially create the illusion of the minimal fractionation of iron isotopes within the sequence. Therefore, a detailed examination of the iron isotope composition in the micro-domains of the loess-paleosol sequence is crucial to elucidate the fractionation processes and mechanisms of iron isotopes during the formation of these sequences. [ABSTRACT FROM AUTHOR]

We previously discovered WS-6 as a new antidepressant in correlation to its function of stimulating neurogenesis. Herein, several different scaffolds (stilbene, 1,3-diphenyl 1-propene, 1,3-diphenyl 2-propene, 1,2-diphenyl acrylo-1-nitrile, 1,2-diphenyl acrylo-2-nitrile, 1,3-diphenyl trimethylamine), further varied through substitutions of twelve amide substituents plus the addition of a methylene unit and an inverted amide, were examined to elucidate the SARs for promoting adult rat neurogenesis. Most of the compounds could stimulate proliferation of progenitors, but just a few chemicals possessing a specific structural profile, exemplified by diphenyl acrylonitrile 29b, 32a, and 32b, showed better activity than the clinical drug NSI-189 in promoting newborn cells differentiation into mature neurons. The most potent diphenyl acrylonitrile 32b had an excellent brain AUC to plasma AUC ratio (B/P = 1.6), suggesting its potential for further development as a new lead. [ABSTRACT FROM AUTHOR]

This paper presents a unified experimental and numerical investigation on the transition from brittle to ductile behavior in a low-porosity sandstone under drained conditions. The experimental results demonstrate a transition in the mechanical behavior from brittle faulting to dilatant ductile flow at room temperature with an increase in effective confining pressure, suggesting that microcracking-controlled local friction is the underlying plastic deformation mechanism. For constitutive modeling, the sandstone is considered as a heterogeneous medium composed of a pores-weakened elastic solid matrix and distributed microcracks. By following a two-step homogenization procedure and irreversible thermodynamics framework, a micromechanics-based elastoplastic damage model incorporating a non-associated local plastic flow rule is formulated, in which the coupling between plasticity, damage and pore pressure is taken into account. In this context, a non-associated macroscopic effective strength criterion as an inherent part of the corresponding model is derived. Originally, a theoretical linear relation between critical state of damage at peak strength and effective confining pressure is established, which is efficient in describing post-peak softening behavior. Comparisons of numerical simulations with experimental data demonstrate that the proposed model effectively reproduces the main features of the sandstone with a brittle-ductile transition. • A transition from brittle to ductile behavior in a saturated low-porosity sandstone is observed. • A non-associated micromechanics-based constitutive model is developed. • A non-associated macroscopic effective strength criterion is derived. • A linear relation between critical damage and effective confining pressure is established. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is one of the most common gynecological tumors with high morbidity and mortality. Altered serum N-glycome has been observed in many diseases, while the association between serum protein N-glycosylation and OC progression remains unclear, particularly for the onset of carcinogenesis from benign neoplasms to cancer. Methods: Herein, a mass spectrometry based high-throughput technique was applied to characterize serum N-glycome profile in individuals with healthy controls, benign neoplasms and different stages of OC. To elucidate the alterations of glycan features in OC progression, an orthogonal strategy with lectin-based ELISA was performed. Results: It was observed that the initiation and development of OC was associated with increased high-mannosylationand agalactosylation, concurrently with decreased total sialylation of serum, each of which gained at least moderately accurate merits. The most important individual N-glycans in each glycan group was H7N2, H3N5 and H5N4S2F1, respectively. Notably, serum N-glycome could be used to accurately discriminate OC patients from benign cohorts, with a comparable or even higher diagnostic score compared to CA125 and HE4. Furthermore, bioinformatics analysis based discriminative model verified the diagnostic performance of serum N-glycome for OC in two independent sets. Conclusions: These findings demonstrated the great potential of serum N-glycome for OC diagnosis and precancerous lesion prediction, paving a new way for OC screening and monitoring. [ABSTRACT FROM AUTHOR]

Synthetic Aperture Radar (SAR) imagery is significant in remote sensing, but the limited spatial resolution results in restricted detail and clarity. Current super-resolution methods confront challenges such as complex network structure, insufficient sensing capability, and difficulty extracting features with local and global dependencies. To address these challenges, DMSC-GAN, a SAR image super-resolution technique based on the c-GAN framework, is introduced in this study. The design objective of DMSC-GAN is to enhance the flexibility and controllability of the model by utilizing conditional inputs to modulate the generated image features. The method uses an encoder–decoder structure to construct a generator and introduces a feature extraction module that combines convolutional operations with Deformable Multi-Head Self-Attention (DMSA). This module can efficiently capture the features of objects of various shapes and extract important background information needed to recover complex image textures. In addition, a multi-scale feature extraction pyramid layer helps to capture image details at different scales. DMSC-GAN combines perceptual loss and feature matching loss and, with the enhanced dual-scale discriminator, successfully extracts features from SAR images for high-quality super-resolution reconstruction. Extensive experiments confirm the excellent performance of DMSC-GAN, which significantly improves the spatial resolution and visual quality of SAR images. This framework demonstrates strong capabilities and potential in advancing super-resolution techniques for SAR images. [ABSTRACT FROM AUTHOR]

Emodin, a natural anthraquinone derivative, possesses anti-proliferative and anti-inflammatory properties in skin diseases. However, little information is available on the efficacy of emodin in treating acne vulgaris (acne). This study aims to investigate the protective effects and potential mechanisms of emodin as an anti-acne agent. In vitro, SZ95 sebocytes was chose to establish an acneigenic cellular model. We found that emodin effectively inhibited proliferation, induced cell cycle arrest and apoptosis of SZ95 sebocytes in a dose-dependent manner. To evaluate the lipid-lowering potential of emodin, we examined the levels of lipid contents and lipogenic transcription factors, and found that both lipid production and protein expression of PPARγ, LXR α/β, and SREBP-1 were decreased after treatment with emodin. Furthermore, our results revealed that emodin inhibited sebaceous lipogenesis induced by insulin-like growth factor 1 (IGF-1), which was accompanied by a potent inhibition of the phosphoinositide-3-kinase (PI3K)/Akt/forkhead box protein O1 (FoxO1) pathway. In detail, emodin augmented the inhibitory effect of isotretinoin and PI3K inhibitor LY294002, while attenuating the activation of IGF-1 on PI3K/Akt/FoxO1 pathway. In addition, emodin could decrease the secretion of pro-inflammatory cytokines IL-6 and IL-8, and suppress the expression of NLRP3, capase-1, IL-1β, and IL-18 in SZ95 sebocytes exposed to Cutibacterium acnes. Overall, our study provides preliminary evidence supporting the anti-growth, anti-lipogenic and anti-inflammatory properties of emodin, indicating the potential therapeutic application of emodin for acne treatment. [ABSTRACT FROM AUTHOR]

Electron cyclotron harmonic (ECH) waves can scatter electrons into the atmosphere causing diffuse aurora with diffusion coefficients depending on the wave frequency. Here we report the Van Allen Probe observations of chirping ECH elements, which are fine structures with a frequency‐chirping rate of ∼kHz/s. 1,834 samples are identified in the 51‐month database and over 93 percent of them exhibit a falling tone pattern. ECH elements cover a broad region from 18 Magnetic Local Time (MLT) through dawn to 14 MLT with L = 4 − 7, and mainly occur in the region of 00–07 MLT with L = 5 − 6. More ECH elements are observed with the occurrence region extending to lower L‐shells during the geomagnetic activity period. Chirping ECH elements can propagate to |MLAT| ∼ 20°, but be confined by the contour of magnetic field strength. The statistical results can be applied on the global simulation of ECH‐induced electron penetration. Plain Language Summary: Electron cyclotron harmonic (ECH) wave plays a critical role in the magnetospheric dynamics by diffusing energetic electrons into the atmosphere. Previous studies show that the diffusion coefficients are very sensitive to the wave frequency. Here based on the Van Allen Probes data, we report the presence of ECH frequency chirping structures (so‐called chirping ECH elements) in the magnetosphere. The duration of ECH elements is comparable with the well‐known chorus elements. Adopting a 51‐month database, we study the statistical properties of such ECH elements. All of the ECH elements occur in the first harmonic band and more than 93 percent of them are falling tones. ECH elements cover a broad range of L = 4 − 7 from 18 MLT through dawn to 14 MLT, and mainly appear in the region L = 5 − 6 at the midnight to dawn sector. It is widely accepted that ECH waves generally occur in the equatorial region. Here the ECH elements can propagate to |MLAT| ∼ 20°. Moreover, when the geomagnetic activities get more intense, more ECH elements can be observed and they can extend to lower L‐shells. The current results could be important for investigating their generation mechanism and quantifying the ECH‐electron resonance process. Key Points: All chirping electron cyclotron harmonic (ECH) elements (1,834 samples) occur in the first harmonic band, showing a distinct preference to falling tone structures (>93%)The chirping ECH elements cover a broad region of radiation belts, with a higher occurrence in the region of 00–07 Magnetic Local Time (MLT) with L = 5 − 6As the AE index increases, the occurrence region of chirping ECH elements extends to lower L‐shells [ABSTRACT FROM AUTHOR]

T cells rely on their T cell receptors (TCRs) to discern foreign antigens presented by human leukocyte antigen (HLA) proteins. The TCRs of an individual contain a record of this individual's past immune activities, such as immune response to infections or vaccines. Mining the TCR data may recover useful information or biomarkers for immune related diseases or conditions. Some TCRs are observed only in the individuals with certain HLA alleles, and thus characterizing TCRs requires a thorough understanding of TCR-HLA associations. The extensive diversity of HLA alleles and the rareness of some HLA alleles present a formidable challenge for this task. Existing methods either treat HLA as a categorical variable or represent an HLA by its alphanumeric name, and have limited ability to generalize to the HLAs that are not seen in the training process. To address this challenge, we propose a neural network-based method named Deep learning Prediction of TCR-HLA association (DePTH) to predict TCR-HLA associations based on their amino acid sequences. We demonstrate that DePTH is capable of making reasonable predictions for TCR-HLA associations, even when neither the HLA nor the TCR have been included in the training dataset. Furthermore, we establish that DePTH can be used to quantify the functional similarities among HLA alleles, and that these HLA similarities are associated with the survival outcomes of cancer patients who received immune checkpoint blockade treatments. Author summary: T cells are critical components of the human immune system. A T cell receptor (TCR) is a protein complex found on the surface of T cells, and it determines the antigens that a T cell recognizes. The TCR repertoire, which is the collection of all the TCRs within an individual, provides rich information about the history and current activities of the immune system. A TCR-antigen interaction is mediated by a protein called human leukocyte antigen (HLA). HLA genes are highly polymorphic in the human population, contributing to the variation of human immune response to different types of antigens. Studying the associations between TCRs and HLAs can help us identify functional TCRs given the HLAs of an individual. To this end, we develop a deep learning method to predict TCR-HLA associations based on their amino acid sequences. This method allows us to borrow information across different HLA genes. We demonstrate that the predictions of our model can be used to quantify the functional similarities of HLA alleles and such similarities are associated with cancer patients' survival outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: The developmental process, divided into four different stages (egg, larva, pupa and adult), is the main reason for their remarkable diversification and expansion of the insect group Holometabola. Advanced morphological techniques have been used to demonstrate the 3D thoracic anatomical structures of the holometalous model organism fruit fly, Drosophila melanogaster, before and after emergence, in order to uncover the transformation process of the muscles, nerves, and gut during development. Skeletal changes affect the original positions of the muscles. The muscles vary in size, not only becoming longer and broader, but also shorter and narrower. Different muscle shapes may appear during development. The number of bundles may also vary. The soft tissues in the body may fix the free ends of the growing muscles, and a strong adult skeleton likely causes the absence of some muscles and tendons. The flight muscles appear very early, probably to achieve full functionality of these very large adult-specific muscles in time. There are some differences during the same developmental period between the two sexes. Most muscles of the larvae and adults with similar attachment positions change their functions from supporting crawling to supporting flying and walking under the control of a more complex ventral nerve cord. The midguts of the larva and the adult are nearly the same. The model organism Drosophila melanogaster, as a species of Holometabola, undergoes a series of transformations during metamorphosis. To deeply understand its development, it is crucial to study its anatomy during the key developmental stages. We describe the anatomical systems of the thorax, including the endoskeleton, musculature, nervous ganglion, and digestive system, from the late pupal stage to the adult stage, based on micro-CT and 3D visualizations. The development of the endoskeleton causes original and insertional changes in muscles. Several muscles change their shape during development in a non-uniform manner with respect to both absolute and relative size; some become longer and broader, while others shorten and become narrower. Muscular shape may vary during development. The number of muscular bundles also increases or decreases. Growing muscles are probably anchored by the tissues in the stroma. Some muscles and tendons are absent in the adult stage, possibly due to the hardened sclerites. Nearly all flight muscles are present by the third day of the pupal stage, which may be due to the presence of more myofibers with enough mitochondria to support flight power. There are sexual differences in the same developmental period. In contrast to the endodermal digestive system, the functions of most thoracic muscles change in the development from the larva to the adult in order to support more complex locomotion under the control of a more structured ventral nerve cord based on the serial homology proposed herein. [ABSTRACT FROM AUTHOR]

Background: Camrelizumab has shown encouraging efficacy in advanced non-small cell lung cancer (NSCLC), either as monotherapy or combined with chemotherapy. However, evidence of neoadjuvant camrelizumab for NSCLC remains lacking. Methods: Patients with NSCLC treated with neoadjuvant camrelizumab-based therapy followed by surgery between December 2020 and September 2021 were retrospectively reviewed. Demographic and clinical data, details of neoadjuvant therapy and surgical information were retrieved. Results: In this multicenter retrospective real-world study, 96 patients were included. Ninety-five patients (99.0%) received neoadjuvant camrelizumab combined with platinum-based chemotherapy, with a median of 2 cycles (range 1–6). The median interval from the last dose to surgery was 33 days (range 13–102 days). Seventy patients (72.9%) underwent minimally invasive surgery. Lobectomy was the most frequent surgical procedure (94 [97.9%]). The median estimated intraoperative blood loss was 100 mL (range 5–1200 mL), and the median operative time was 3.0 h (range 1.5–6.5 h). The R0 resection rate was 93.8%. Twenty-one patients (21.9%) experienced postoperative complications, with the most common being cough and pain (both 6 [6.3%]). The overall response rate was 77.1% (95% CI 67.4–85.0%), and the disease control rate was 93.8% (95% CI 86.9–97.7%). Twenty-six patients (27.1%, 95% CI 18.5–37.1%) had pathological complete response. Neoadjuvant treatment-related adverse events of grade ≥ 3 were reported in seven patients (7.3%), with the most frequent being abnormal liver enzymes (two [2.1%]). No treatment-related deaths were reported. Conclusion: The real-world data indicated that camrelizumab-based therapy had promising efficacy for NSCLC in the neoadjuvant setting, with manageable toxicities. Prospective studies investigating neoadjuvant camrelizumab are warranted. [ABSTRACT FROM AUTHOR]

To establish a pre-test probability model of coronary heart disease (CHD) combined with cardiopulmonary exercise test (CPET) indexes and to compare the clinical effectiveness with Duke clinical score (DCS) and updated Diamond-Forrester model (UDFM), thus further explore the predictive value. 342 cases were used to establish the prediction model equation and another 80 cases were used to verify the effectiveness. The patients were divided into CHD group (n = 157) and non-CHD group (n = 185) according to coronary artery stenosis degree >50% or not. Combining DCS and UDFM as reference models with CPET indexes, a multivariate logistic regression model was established. The area under the ROC curve of the three models were calculated to compare the predictive effectiveness. There were significant differences in gender, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave and ST-T change between two groups (P < 0.01), as well as age, LVEF, heart rate at anaerobic domain, peak oxygen uptake in kilograms of body weight, percentage of peak oxygen uptake to the predicted value, the oxygen uptake efficiency slope and carbon dioxide ventilation equivalent slope (P < 0.05). Multivariate analysis showed gender, age, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave, ST-T change, and peak oxygen pulse were independent risk factors of CHD. The pre-test probability model of CHD combined with CPET indexes has good distinguish and calibrate ability, its prediction accuracy is slightly better than DCS and UDFM, which still needs to be verified externally in more samples. [ABSTRACT FROM AUTHOR]

To establish a pre-test probability model of coronary heart disease (CHD) combined with cardiopulmonary exercise test (CPET) indexes and to compare the clinical effectiveness with Duke clinical score (DCS) and updated Diamond-Forrester model (UDFM), thus further explore the predictive value. 342 cases were used to establish the prediction model equation and another 80 cases were used to verify the effectiveness. The patients were divided into CHD group (n = 157) and non-CHD group (n = 185) according to coronary artery stenosis degree >50% or not. Combining DCS and UDFM as reference models with CPET indexes, a multivariate logistic regression model was established. The area under the ROC curve of the three models were calculated to compare the predictive effectiveness. There were significant differences in gender, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave and ST-T change between two groups (P < 0.01), as well as age, LVEF, heart rate at anaerobic domain, peak oxygen uptake in kilograms of body weight, percentage of peak oxygen uptake to the predicted value, the oxygen uptake efficiency slope and carbon dioxide ventilation equivalent slope (P < 0.05). Multivariate analysis showed gender, age, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave, ST-T change, and peak oxygen pulse were independent risk factors of CHD. The pre-test probability model of CHD combined with CPET indexes has good distinguish and calibrate ability, its prediction accuracy is slightly better than DCS and UDFM, which still needs to be verified externally in more samples. [ABSTRACT FROM AUTHOR]

A laser scanning strategy for fabricating deep surface grooves using a continuous-wave fiber laser was investigated in this study. Because the low productivity of short-pulsed-wave lasers limits their application to a small scale, a continuous-wave (CW) fiber laser that can provide a high power density was used for the rapid fabrication of deep grooves. An innovative tailored laser scanning strategy of fabricating patterned deep grooves was analytically designed based on the power density and interaction time. Considering the thermophysical properties of the material, controlled laser processing parameters were determined for fabricating surface grooves with rectangular and chevron cross-sectional patterns. To confirm the usefulness of the research results, the scanning strategy obtained in this study was applied for achieving high-quality joining between injection-molded metal–plastic hybrids (MPHs). A deep-surface-grooved A5052 aluminum alloy sheet was bonded to two plastics, polyamide and polypropylene, via injection molding. Lap shear tensile tests of the MPHs revealed their significantly enhanced joining strength owing to a better mechanical interlocking of the groove. The developed laser scanning strategy using a CW fiber laser can be widely applied in the fabrication of deep grooves of various cross-sections with high reliability. [ABSTRACT FROM AUTHOR]

In the research on water splitting at neutral pH, phosphorus-containing transition metal oxyhydroxides are often employed for catalyzing the oxygen evolution reaction (OER). We investigated a cobalt–phosphate catalyst (CoCat) representing this material class. We found that CoCat films prepared with potassium phosphate release phosphorus in phosphate-free electrolytes within hours, contrasting orders of magnitude's faster K+ release. For P speciation and binding mode characterization, we performed technically challenging X-ray absorption spectroscopy experiments at the P K-edge and analyzed the resulting XANES and EXAFS spectra. The CoCat-internal phosphorus is present in the form of phosphate ions. Most phosphate species are likely linked to cobalt ions in Co–O–PO3 motifs, where the connecting oxygen could be a terminal or bridging ligand in Co-oxide fragments (P–Co distance, ~3.1 Å), with additional ionic bonds to K+ ions (P–K distance, ~3.3 Å). The phosphate coordination bond is stronger than the ionic K+-binding, explaining the strongly diverging ion release rates of phosphate and K+. Our results support a structural role of phosphate in the CoCat, with these ions binding at the margins of Co-oxide fragments, thereby limiting the long-range material ordering. The relations of catalyst-internal phosphate ions to cobalt's redox-state changes, proton transfer, and catalytic activity are discussed. [ABSTRACT FROM AUTHOR]

Research on biomarker-driven therapy and immune check-point blockade in non-small cell lung cancer (NSCLC) is rapidly evolving. The width and depth of clinical trials have also dramatically improved in an unprecedented speed. The personalized treatment paradigm evolved every year. In this review, we summarize the promising agents that have shifted the treatment paradigm for NSCLC patients across all stages, including targeted therapy and immunotherapy using checkpoint inhibitors. Based on recent evidence, we propose treatment algorithms for NSCLC and propose several unsolved clinical issues, which are being explored in ongoing clinical trials. The results of these trials are likely to impact future clinical practice. [ABSTRACT FROM AUTHOR]

Background: The tumor-adipose microenvironment (TAME) is characterized by the enrichment of adipocytes, and is considered a special ecosystem that supports cancer progression. However, the heterogeneity and diversity of adipocytes in TAME remains poorly understood. Methods: We conducted a single-cell RNA sequencing analysis of adipocytes in mouse and human white adipose tissue (WAT). We analyzed several adipocyte subtypes to evaluate their relationship and potential as prognostic factors for overall survival (OS). The potential drugs are screened by using bioinformatics methods. The tumor-promoting effects of a typical adipocyte subtype in breast cancer are validated by performing in vitro functional assays and immunohistochemistry (IHC) in clinical samples. Results: We profiled a comprehensive single-cell atlas of adipocyte in mouse and human WAT and described their characteristics, origins, development, functions and interactions with immune cells. Several cancer-associated adipocyte subtypes, namely DPP4+ adipocytes in visceral adipose and ADIPOQ+ adipocytes in subcutaneous adipose, are identified. We found that high levels of these subtypes are associated with unfavorable outcomes in four typical adipose-associated cancers. Some potential drugs including Trametinib, Selumetinib and Ulixertinib are discovered. Emphatically, knockdown of adiponectin receptor 1 (AdipoR1) and AdipoR2 impaired the proliferation and invasion of breast cancer cells. Patients with AdipoR2-high breast cancer display significantly shorter relapse-free survival (RFS) than those with AdipoR2-low breast cancer. Conclusion: Our results provide a novel understanding of TAME at the single-cell level. Based on our findings, several adipocyte subtypes have negative impact on prognosis. These cancer-associated adipocytes may serve as key prognostic predictor and potential targets for treatment in the future. [ABSTRACT FROM AUTHOR]

In organic purity assessment, chromatography separation with a suitable detector is required. Diode array detection (DAD) has been a widely used technique for high-performance liquid chromatography (HPLC) analyses, but its application is limited to compounds with sufficient UV chromophores. Charged aerosol detector (CAD), as a mass-dependent detector, is advantageous for providing a nearly uniform response for analytes, regardless of their structures. In this study, 11 non-volatile compounds with/without UV chromophores were analyzed by CAD using continuous direct injection mode. The RSDs of CAD responses were within 17%. For saccharides and bisphenols, especially, the RSDs were lower (2.12% and 8.14%, respectively). Since bisphenols exist in UV chromophores, their HPLC–DAD responses were studied and compared with CAD responses, with CAD showing a more uniform response. Besides, the key parameters of HPLC-CAD were optimized and the developed method was verified using a Certified Reference Material (CRM, dulcitol, GBW06144). The area normalization result of dulcitol measured by HPLC-CAD was 99.89% ± 0.02% (n = 6), consistent with the certified value of 99.8% ± 0.2% (k = 2). The result of this work indicated that the HPLC-CAD method could be a good complementary tool to traditional techniques for the purity assessment of organic compounds, especially for compounds lacking UV chromophores. [ABSTRACT FROM AUTHOR]

Background: The long-term prognosis of patients with hepatocellular carcinoma (HCC) after surgery remains far from satisfactory, especially in patients with microvascular invasion (MVI). This study aimed to evaluate the potential survival benefit from adjuvant lenvatinib for patients with HCC and MVI. Methods: Patients with HCC after curative hepatectomy were reviewed. All patients were divided into 2 groups according to adjuvant lenvatinib. Propensity score matching (PSM) analysis was used to reduce selection bias and make the results more robust. Survival curves are shown by the Kaplan-Meier (K-M) analysis and compared by the Log-rank test. Univariate and multivariate Cox regression analyses were performed to determine the independent risk factors. Results: Of 179 patients enrolled in this study, 43 (24%) patients received adjuvant lenvatinib. After PSM analysis, 31 pairs of patients were enrolled for further analysis. Survival analysis before and after PSM analysis showed a better prognosis in the adjuvant lenvatinib group (all P <.05). The adverse events associated with oral lenvatinib were acceptable. Multivariate Cox regression analysis showed that adjuvant lenvatinib was an independent protective factor for improving overall survival (OS) (hazard ratio [HR] = 0.455, 95% confidence interval [CI] = 0.249-0.831, P =.001) and recurrence-free survival (RFS) (HR = 0.523, 95% CI = 0.308-0.886, P =.016). Conclusions: Postoperative adjuvant targeted therapy can improve the long-term prognosis of patients with HCC and MVI. Therefore, in clinical practice, oral lenvatinib should be recommended for patients with HCC and MVI to decrease tumor recurrence and improve long-term survival. [ABSTRACT FROM AUTHOR]

Electron cyclotron harmonic (ECH) waves, which are responsible for the diffuse aurora, are usually observed with the strongest intensity in the first band. Here, we present observations of enhanced higher‐band ECH with wave intensities above 10−3 mV2m−2 Hz−1 by Van Allen Probes. Fully thermal simulation results indicate that these waves can be locally excited by the observed electron distributions, and higher plasma density and lower magnetic strength are favorable for generating the enhanced higher‐band ECH. The pitch angle diffusion coefficient Dαα $\left\langle {D}_{\alpha \alpha }\right\rangle $ of the higher‐band ECH can exceed 10−5 s−1 inside the loss cone for energetic electrons (300 eV–∼15 keV), greater than the momentum diffusion coefficient Dpp $\left\langle {D}_{pp}\right\rangle $ by ∼100 times. It is suggested that the enhanced higher‐band ECH can also efficiently scatter these electrons into the loss cone and contribute to the diffuse aurora. Plain Language Summary: Electron cyclotron harmonic (ECH) waves are electrostatic emissions usually observed with the strongest intensity in the first band. Numerous works have demonstrated that the first‐band ECH waves can be responsible for diffuse auroral electron precipitation. However, so far the role of higher‐band ECH waves has not been confirmed. Here, we report an enhanced higher‐band ECH event with wave intensities above 10−3 mV2m−2 Hz−1 from Van Allen Probes. Using the realistic parameters, we conduct fully thermal simulations to investigate the generation of such ECH. The results indicate that growth rates can well reproduce the observed wave spectral characteristics in all four harmonic bands, and the higher density and lower magnetic field strength are favorable for generating enhanced higher‐band ECH. We calculate the diffusion coefficients to estimate the effect of the higher‐band ECH on electrons. The pitch angle diffusion coefficients induced by higher‐band ECH are ∼2 orders of magnitude greater than the momentum diffusion coefficients over a broad pitch angle range and exceed 10−5 s−1 inside the loss cone for energetic electrons. This indicates that the enhanced higher‐band ECH can also efficiently scatter these energetic electrons into the loss cone and potentially contribute to the diffuse aurora, similar to the first‐band ECH. Key Points: Enhanced higher‐band Electron cyclotron harmonic (ECH) waves with electric spectral density above 10−3 mV2m−2 Hz−1 were observed by Van Allen ProbesFully thermal simulations show that higher density and lower magnetic strength are favorable for generating enhanced higher‐band ECHEnhanced higher‐band ECH can cause efficient scattering loss of energetic electrons and contribute to the diffuse aurora [ABSTRACT FROM AUTHOR]

Coronavirus infection induces a variety of cellular antiviral responses either dependent on or independent of type I interferons (IFNs). Our previous studies using Affymetrix microarray and transcriptomic analysis revealed the differential induction of three IFN-stimulated genes (ISGs), IRF1, ISG15 and ISG20, by gammacoronavirus infectious bronchitis virus (IBV) infection of IFN-deficient Vero cells and IFN-competent, p53-defcient H1299 cells, respectively. In this report, the induction kinetics and anti-IBV functions of these ISGs as well as mechanisms underlying their differential induction are characterized. The results confirmed that these three ISGs were indeed differentially induced in H1299 and Vero cells infected with IBV, significantly more upregulation of IRF1, ISG15 and ISG20 was elicited in IBV-infected Vero cells than that in H1299 cells. Induction of these ISGs was also detected in cells infected with human coronavirus-OC43 (HCoV-OC43) and porcine epidemic diarrhea virus (PEDV), respectively. Manipulation of their expression by overexpression, knockdown and/or knockout demonstrated that IRF1 played an active role in suppressing IBV replication, mainly through the activation of the IFN pathway. However, a minor, if any, role in inhibiting IBV replication was played by ISG15 and ISG20. Furthermore, p53, but not IRF1, was implicated in regulating the IBV infection-induced upregulation of ISG15 and ISG20. This study provides new information on the mechanisms underlying the induction of these ISGs and their contributions to the host cell antiviral response during IBV infection. • IBV infection of H1299 and IFN-β-deficient Vero cells differentially regulates the expression of IRF1, ISG15 and ISG20. • Overexpression of IRF1 suppresses IBV replication mainly through the induction of IFN pathways. • The endogenous IRF1 plays a minor role in the inhibition of IBV replication and in the induction of ISG15 and ISG20. • Overexpression of ISG15 and ISG20 does not significantly suppress IBV replication. • IBV-induced ISG15 and ISG20 expression is partially p53-dependent, but not by IRF1. [ABSTRACT FROM AUTHOR]

Magnetosonic (MS) wave is one of the most common electromagnetic emissions in the magnetosphere, while quasi‐electrostatic magnetosonic (QEMS) waves are seldom observed. Here we present an interesting QEMS event detected by Van Allen Probe A on 9 January 2014, in which the presence of multi‐band QEMS emissions shows evident correlations with relatively low plasma densities (∼10 cm−3) and enhancements of suprathermal (∼10 − 100 eV) proton fluxes. Based on the observed proton distributions, simulations demonstrate very similar profiles to the observed QEMS in the wave spectral characteristics. Parametric studies indicate that the QEMS growth rate can increase by ∼20 times with the plasma density decreasing from 50 to 10 cm−3. Effective growth rates of higher‐band QEMS occur when the suprathermal proton population is sufficiently large. This study reveals that low densities and large suprathermal proton populations are favorable for generating distinct multi‐band QEMS in the magnetosphere. Plain Language Summary: Magnetosonic (MS) wave is one of the most common electromagnetic emissions in the magnetosphere, while quasi‐electrostatic magnetosonic (QEMS) wave is seldom observed. Here we report an interesting event detected by Van Allen Probe A on 9 January 2014, in which multi‐band QEMS emissions occurred exactly corresponding to the presence of low plasma densities (∼10 cm−3) and enhancements of suprathermal (∼10 − 100 eV) proton fluxes. Based on the observed data of three typical time intervals, we perform simulations to investigate how the plasma density and suprathermal protons affect the generation of QEMS. Our results are quite comparable with the observations in the patterns of wave intensity and frequency characteristics. We then adjust the parameters and find that QEMS growth rate increases by ∼20 times with the plasma density decreasing from 50 to 10 cm−3. Effective growth rates of higher‐band QEMS only occur when the suprathermal proton population is ≥0.75 cm−3. These results demonstrate that the low plasma density is propitious for generating distinct QEMS, and a sufficiently large suprathermal proton population is beneficial for forming the multi‐band structure of QEMS. Key Points: Multi‐band quasi‐electrostatic magnetosonic (QEMS) was observed exactly corresponding to low plasma densities and enhanced suprathermal proton fluxesSimulations indicate that QEMS growth rate can increase by about 20 times with the plasma density decreasing from 50 to 10 cm−3A large suprathermal (∼10–100 eV) proton population is favorable for extending the QEMS to higher bands [ABSTRACT FROM AUTHOR]

The warping effects may predominate in geometrically nonlinear analysis of open cross-section members. The formulation of conventional beam-column elements incorporating the warping effects is cumbersome due to the method considering the inconsistency between the shear center and centroid. To develop a concise warping element formulation, this paper presents a transformation matrix to integrate the inconsistent effects into the element stiffness matrix. The co-rotational (CR) method used to establish the element equilibrium conditions in the geometrically nonlinear analysis is adopted to simplify the element formulation and improve the efficiency of nonlinear analysis. A new beam-column element explicitly considering the warping deformation and the Wagner effects is derived based on the CR method and the Euler–Bernoulli beam theory. A detailed kinematic description is provided for considering large deflections and rigid body motions. Based on the mechanical characteristic, the coordinate and the rigid body motion transformation matrices are given. The secant relationship is developed to evaluate the element internal forces accurately and effectively in each iteration. Several verification examples are provided to validate the proposed method's reliability and robustness. The verifications demonstrate that the proposed element leads to considerable computational advantages. The results of this paper are useful for future upgrading of frame analysis software with warping degrees-of-freedom (DOFs). [ABSTRACT FROM AUTHOR]

Simple Summary: A newly identified non-AUG-initiated ORF, ORF3a, encoded by members of the genus Polerovirus, is required for long-distance movement in plants. However, its functions in host protein interactions still remain unclear. Here, we systemically investigated Brassica yellows virus (BrYV)-P3a interacting proteins in plants. In total, 138 genes with annotations were obtained. Furthermore, Arabidopsis thaliana purine permease 14, glucosinolate transporter 1, and nitrate transporter 1.7 were verified to interact with P3a in vivo and were downregulated in response to BrYV during the late stages of viral infection. We used pup14, gtr1, and nrt1.7, the T-DNA insertion mutants, to preliminarily characterize their roles in the BrYV infection process. Viruses are obligate parasites that only undergo genomic replication in their host organisms. ORF3a, a newly identified non-AUG-initiated ORF encoded by members of the genus Polerovirus, is required for long-distance movement in plants. However, its interactions with host proteins still remain unclear. Here, we used Brassica yellows virus (BrYV)-P3a as bait to screen a plant split-ubiquitin-based membrane yeast two-hybrid (MYTH) cDNA library to explain the functional role of P3a in viral infections. In total, 138 genes with annotations were obtained. Bioinformatics analyses revealed that the genes from carbon fixation in photosynthetic, photosynthesis pathways, and MAPK signaling were affected. Furthermore, Arabidopsis thaliana purine permease 14 (AtPUP14), glucosinolate transporter 1 (AtGTR1), and nitrate transporter 1.7 (AtNRT1.7) were verified to interact with P3a in vivo. P3a and these three interacting proteins mainly co-localized in the cytoplasm. Expression levels of AtPUP14, AtGTR1, and AtNRT1.7 were significantly reduced in response to BrYV during the late stages of viral infection. In addition, we characterized the roles of AtPUP14, AtGTR1, and AtNRT1.7 in BrYV infection in A. thaliana using T-DNA insertion mutants, and the pup14, gtr1, and nrt1.7 mutants influenced BrYV infection to different degrees. [ABSTRACT FROM AUTHOR]

Purpose: This study was to explore whether Ginkgo biloba extract (GBE) improve memory impairment by alleviating neuroinflammation signaling in mice with status epilepticus. Methods: The status epilepticus (SE) mice model was established by pilocarpine and treated with 100 mg / kg of GBE for 14 days. Spontaneous alternation of Y‐maze and new object recognition were used to explore memory impairment. To examine glial cell activation, we performed immunohistochemistry and immunofluorescence staining. The activation of NF‐κB signaling and the expression level of lncRNA‐COX2 were detected by Western blot and qRT‐PCR, respectively. Adeno‐associated virus lncRNA‐COX2 was injected into mice for overexpression of lncRNA‐COX2. Results: After GBE treatment, the spontaneous alternation rate and the recognition coefficient in SE mice were both increased. Moreover, activation of glial cells, NF‐κB signaling and lncRNA‐COX2 were significantly decreased in SE mice. In the GBE‐treated SE mice with lncRNA‐COX2 overexpression, NF‐κB signaling was up‐regulated again; the reduced level of inflammation factors was reversed; the GBE‐rescued spontaneous alternation rate of Y‐maze was eliminated. Conclusion: Our results suggested that GBE reduces the hippocampal inflammation by down‐regulating lncRNA‐COX2 / NF‐κB signaling in the SE mice, leading to the decrease of neuronal damage and the improvement of memory functions. [ABSTRACT FROM AUTHOR]

In this paper, we address the makeup transfer and removal tasks simultaneously, which aim to transfer the makeup from a reference image to a source image and remove the makeup from the with-makeup image respectively. Existing methods have achieved much advancement in constrained scenarios, but it is still very challenging for them to transfer makeup between images with large pose and expression differences, or handle makeup details like blush on cheeks or highlight on the nose. In addition, they are hardly able to control the degree of makeup during transferring or to transfer a specified part in the input face. These defects limit the application of previous makeup transfer methods to real-world scenarios. In this work, we propose a Pose and expression robust Spatial-aware GAN (abbreviated as PSGAN++). PSGAN++ is capable of performing both detail-preserving makeup transfer and effective makeup removal. For makeup transfer, PSGAN++ uses a Makeup Distill Network (MDNet) to extract makeup information, which is embedded into spatial-aware makeup matrices. We also devise an Attentive Makeup Morphing (AMM) module that specifies how the makeup in the source image is morphed from the reference image, and a makeup detail loss to supervise the model within the selected makeup detail area. On the other hand, for makeup removal, PSGAN++ applies an Identity Distill Network (IDNet) to embed the identity information from with-makeup images into identity matrices. Finally, the obtained makeup/identity matrices are fed to a Style Transfer Network (STNet) that is able to edit the feature maps to achieve makeup transfer or removal. To evaluate the effectiveness of our PSGAN++, we collect a Makeup Transfer In the Wild (MT-Wild) dataset that contains images with diverse poses and expressions and a Makeup Transfer High-Resolution (MT-HR) dataset that contains high-resolution images. Experiments demonstrate that PSGAN++ not only achieves state-of-the-art results with fine makeup details even in cases of large pose/expression differences but also can perform partial or degree-controllable makeup transfer. Both the code and the newly collected datasets will be released at https://github.com/wtjiang98/PSGAN. [ABSTRACT FROM AUTHOR]

Quercetin and kaempferol are flavonoids widely present in fruits, vegetables, and medicinal plants. They have attracted much attention due to their antioxidant, anti-inflammatory, anticancer, antibacterial, and neuroprotective properties. As the guarantee cells in direct contact with germ cells, Sertoli cells exert the role of support, nutrition, and protection in spermatogenesis. In the current study, network pharmacology was used to explore the targets and signaling pathways of quercetin and kaempferol in treating spermatogenic disorders. In vitro experiments were integrated to verify the results of quercetin and kaempferol against heat stress-induced Sertoli cell injury. The online platform was used to analyze the GO biological pathway and KEGG pathway. The results of the network pharmacology showed that quercetin and kaempferol intervention in spermatogenesis disorders were mostly targeting the oxidative response to oxidative stress, the ROS metabolic process and the NFκB pathway. The results of the cell experiment showed that Quercetin and kaempferol can prevent the decline of cell viability induced by heat stress, reduce the expression levels of HSP70 and ROS in Sertoli cells, reduce p-NF-κB-p65 and p-IκB levels, up-regulate the expression of occludin, vimentin and F-actin in Sertoli cells, and protect cell structure. Our research is the first to demonstrate that quercetin and kaempferol may exert effects in resisting the injury of cell viability and structure under heat stress. [ABSTRACT FROM AUTHOR]

Camouflaged object detection (COD) aims to identify the objects that conceal themselves in natural scenes. Accurate COD suffers from a number of challenges associated with low boundary contrast and the large variation of object appearances, e.g., object size and shape. To address these challenges, we propose a novel Context-aware Cross-level Fusion Network ($\text{C}^{2}\text{F}$ -Net), which fuses context-aware cross-level features for accurately identifying camouflaged objects. Specifically, we compute informative attention coefficients from multi-level features with our Attention-induced Cross-level Fusion Module (ACFM), which further integrates the features under the guidance of attention coefficients. We then propose a Dual-branch Global Context Module (DGCM) to refine the fused features for informative feature representations by exploiting rich global context information. Multiple ACFMs and DGCMs are integrated in a cascaded manner for generating a coarse prediction from high-level features. The coarse prediction acts as an attention map to refine the low-level features before passing them to our Camouflage Inference Module (CIM) to generate the final prediction. We perform extensive experiments on three widely used benchmark datasets and compare $\text{C}^{2}\text{F}$ -Net with state-of-the-art (SOTA) models. The results show that $\text{C}^{2}\text{F}$ -Net is an effective COD model and outperforms SOTA models remarkably. Further, an evaluation on polyp segmentation datasets demonstrates the promising potentials of our $\text{C}^{2}\text{F}$ -Net in COD downstream applications. Our code is publicly available at: https://github.com/Ben57882/C2FNet-TSCVT [ABSTRACT FROM AUTHOR]

Given a natural language expression and an image/video, the goal of referring segmentation is to produce the pixel-level masks of the entities described by the subject of the expression. Previous approaches tackle this problem by implicit feature interaction and fusion between visual and linguistic modalities in a one-stage manner. However, human tends to solve the referring problem in a progressive manner based on informative words in the expression, i.e., first roughly locating candidate entities and then distinguishing the target one. In this paper, we propose a cross-modal progressive comprehension (CMPC) scheme to effectively mimic human behaviors and implement it as a CMPC-I (Image) module and a CMPC-V (Video) module to improve referring image and video segmentation models. For image data, our CMPC-I module first employs entity and attribute words to perceive all the related entities that might be considered by the expression. Then, the relational words are adopted to highlight the target entity as well as suppress other irrelevant ones by spatial graph reasoning. For video data, our CMPC-V module further exploits action words based on CMPC-I to highlight the correct entity matched with the action cues by temporal graph reasoning. In addition to the CMPC, we also introduce a simple yet effective Text-Guided Feature Exchange (TGFE) module to integrate the reasoned multimodal features corresponding to different levels in the visual backbone under the guidance of textual information. In this way, multi-level features can communicate with each other and be mutually refined based on the textual context. Combining CMPC-I or CMPC-V with TGFE can form our image or video version referring segmentation frameworks and our frameworks achieve new state-of-the-art performances on four referring image segmentation benchmarks and three referring video segmentation benchmarks respectively. Our code is available at https://github.com/spyflying/CMPC-Refseg. [ABSTRACT FROM AUTHOR]

Vision and language understanding techniques have achieved remarkable progress, but currently it is still difficult to well handle problems involving very fine-grained details. For example, when the robot is told to “bring me the book in the girl’s left hand”, most existing methods would fail if the girl holds one book respectively in her left and right hand. In this work, we introduce a new task named human-centric relation segmentation (HRS), as a fine-grained case of HOI-det. HRS aims to predict the relations between the human and surrounding entities and identify the relation-correlated human parts, which are represented as pixel-level masks. For the above exemplar case, our HRS task produces results in the form of relation triplets $\langle$ 〈 girl [left hand], hold, book $\rangle$ 〉 and exacts segmentation masks of the book, with which the robot can easily accomplish the grabbing task. Correspondingly, we collect a new Person In Context (PIC) dataset for this new task, which contains 17,122 high-resolution images and densely annotated entity segmentation and relations, including 141 object categories, 23 relation categories and 25 semantic human parts. We also propose a Simultaneous Matching and Segmentation (SMS) framework as a solution to the HRS task. It contains three parallel branches for entity segmentation, subject object matching and human parsing respectively. Specifically, the entity segmentation branch obtains entity masks by dynamically-generated conditional convolutions; the subject object matching branch detects the existence of any relations, links the corresponding subjects and objects by displacement estimation and classifies the interacted human parts; and the human parsing branch generates the pixelwise human part labels. Outputs of the three branches are fused to produce the final HRS results. Extensive experiments on PIC and V-COCO datasets show that the proposed SMS method outperforms baselines with the 36 FPS inference speed. Notably, SMS outperforms the best performing baseline $m$ m -KERN with only 17.6 percent time cost. The dataset and code will be released at http://picdataset.com/challenge/index/. [ABSTRACT FROM AUTHOR]

Hepatocyte nuclear factor alpha (HNF1α), endoplasmic reticulum (ER) stress, and hepatocyte apoptosis contribute to severe acute exacerbation (SAE) of liver injury. Here, we explore HNF1α–ER stress-hepatocyte apoptosis interaction in liver injury. LO2, HepG2 and SK-Hep1 cells were treated with thapsigargin (TG) or tunicamycin (TM) to induce ER stress. Carbon tetrachloride (CCl4) was used to induce acute liver injury in mice. Low-dose lipopolysaccharide (LPS) exacerbated liver injury in CCl4-induced mice. Significant apoptosis, HNF1α upregulation, and nuclear factor kappa B (NF-κB) activation were observed in human-derived hepatocytes during ER stress. Knockdown of Rela, NF-κB p65, inhibited the HNF1α upregulation. Following CCl4 treatment ER stress, apoptosis, HNF1α expression and RelA phosphorylation were significantly increased in mice. HNF1α knockdown reduced activating transcription factor 4 (ATF4) expression, and aggravated ER stress as well as hepatocyte apoptosis in vivo and in vitro. The double fluorescent reporter gene assay confirmed that HNF1α regulated the transcription of ATF4 promoter. LPS aggravated CCl4-induced liver injury and reduced HNF1α, and ATF4 expression. Therefore, in combination, HNF1α and ER stress could be mutually regulated forming a feedback loop, which helps in protecting the injured liver by down-regulating hepatocyte apoptosis. Low-dose LPS aggravates hepatocyte apoptosis and promotes the SAE of liver injury by interfering with the feedback regulation of HNF1α and ER stress in acute liver injury. [ABSTRACT FROM AUTHOR]

Wind speed is an important meteorological parameter, whose simulation is influenced by various physical process parameterizations. However, the impact of cumulus parameterization schemes (CPSs) on wind speed simulation at the climate scale has not been sufficiently investigated in previous studies. Using the Advanced Research version of the Weather Research and Forecasting model (ARWv3) and hydrostatic wind speed change equation, we assessed the effects of four CPSs on a 10 m wind speed simulation over mainland China in the summer of 2003. In general, different CPSs can reproduce the wind speed distribution. Meanwhile, the sensitivity of wind speed simulation to CPSs was found to be the highest in East and southern China, followed by the Tibetan Plateau, and then Northwest China. We found that the main physical processes influencing wind speed (i.e., the pressure gradient (PRE), diffusion (DFN), and convection (CON) terms) vary greatly with sub-regions. CPSs mainly affect the secondary CON that regulates the balance between the dominant terms PRE and DFN, and also has a significant effect on PRE. For example, for CON, the difference index (DIF) between the Kain–Fritsch (KF) and previous KF (pKF) CPSs is larger than 20%, corresponding to a PRE DIF of about 14%. The term of local wind speed change (Vt) is significantly more sensitive to the CPSs than the other terms with a DIF of 283% over the Tibetan Plateau, suggesting high CPS sensitivity of the simulated wind speed. In addition, we explained the causes of the CPS-induced sensitivities. This work helps understand the Weather Research and Forecasting model (WRF) performance and emphasizes the importance of the CPS choice in simulating/forecasting wind speed. [ABSTRACT FROM AUTHOR]

The heterogeneity and the complex cellular architecture have a crucial effect on breast cancer progression and response to treatment. However, deciphering the neoplastic subtypes and their spatial organization is still challenging. Here, we combine single-nucleus RNA sequencing (snRNA-seq) with a microarray-based spatial transcriptomics (ST) to identify cell populations and their spatial distribution in breast cancer tissues. Malignant cells are clustered into distinct subpopulations. These cell clusters not only have diverse features, origins and functions, but also emerge to the crosstalk within subtypes. Furthermore, we find that these subclusters are mapped in distinct tissue regions, where discrepant enrichment of stromal cell types are observed. We also inferred the abundance of these tumorous subpopulations by deconvolution of large breast cancer RNA-seq cohorts, revealing differential association with patient survival and therapeutic response. Our study provides a novel insight for the cellular architecture of breast cancer and potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

In this paper, we target at the Fine-grAined human-Centric Tracklet Segmentation (FACTS) problem, where 12 human parts, e.g., face, pants, left-leg, are segmented. To reduce the heavy and tedious labeling efforts, FACTS requires only one labeled frame per video during training. The small size of human parts and the labeling scarcity makes FACTS very challenging. Considering adjacent frames of videos are continuous and human usually do not change clothes in a short time, we explicitly consider the pixel-level and frame-level context in the proposed Temporal Context segmentation Network (TCNet). On the one hand, optical flow is on-line calculated to propagate the pixel-level segmentation results to neighboring frames. On the other hand, frame-level classification likelihood vectors are also propagated to nearby frames. By fully exploiting the pixel-level and frame-level context, TCNet indirectly uses the large amount of unlabeled frames during training and produces smooth segmentation results during inference. Experimental results on four video datasets show the superiority of TCNet over the state-of-the-arts. The newly annotated datasets can be downloaded via http://liusi-group.com/projects/FACTS for the further studies. [ABSTRACT FROM AUTHOR]

Motivation Enhanced by contemporary computational advances, the prediction of drug–target interactions (DTIs) has become crucial in developing de novo and effective drugs. Existing deep learning approaches to DTI prediction are frequently beleaguered by a tendency to overfit specific molecular representations, which significantly impedes their predictive reliability and utility in novel drug discovery contexts. Furthermore, existing DTI networks often disregard the molecular size variance between macro molecules (targets) and micro molecules (drugs) by treating them at an equivalent scale that undermines the accurate elucidation of their interaction. Results We propose a novel DTI network with a differential-scale scheme to model the binding site for enhancing DTI prediction, which is named as BindingSiteDTI. It explicitly extracts multiscale substructures from targets with different scales of molecular size and fixed-scale substructures from drugs, facilitating the identification of structurally similar substructural tokens, and models the concealed relationships at the substructural level to construct interaction feature. Experiments conducted on popular benchmarks, including DUD-E, human, and BindingDB, shown that BindingSiteDTI contains significant improvements compared with recent DTI prediction methods. Availability and implementation The source code of BindingSiteDTI can be accessed at https://github.com/MagicPF/BindingSiteDTI. [ABSTRACT FROM AUTHOR]

Treating the high water-content sludge with vacuum-assisted prefabricated horizontal drains (PHDs) placed inside, geotextile tubes have the advantage of multiple drainage paths, and geomembrane tubes have the superiority of high vacuum maintenance. Therefore, converting the geotextile tube into a geomembrane tube during slurry dewatering is an effective measure for greater dewatering efficiency and better dehydration effect. In this study, a profound plane-strain consolidation model considering two-dimensional seepage is developed for explaining the dewatering mechanism of sludge in the geo-tubes. Analytical solutions are given and validated by the experiment. The impact of major variables on tube efficiency is further discussed to reference the practice design. Parametric analyses reveal the critical time corresponding to the optimal efficiency of the geotextile tube, after which its consolidation efficiency decreases significantly. However, the consolidation efficiency of a geomembrane tube increases throughout the duration. Consequently, a switching point corresponding to the iso-efficiency state of the geotextile tube and geomembrane tube can be determined for the tube conversion. [ABSTRACT FROM AUTHOR]

[Display omitted] • Increased paramylon productivity was achieved using hydrolysate-based medium. • Cell immobilisation was assessed for efficient paramylon production by E. gracilis. • Waste sponge was demonstrated to be promising for efficient paramylon production. • Productivity of 1.77 g/L/day was achieved using waste-based cell immobilisation. Microalga represents a promising platform for numerous valuable bioproducts, but the production cost and efficiency remain major challenges for the industrial implementation. In this study, the production of paramylon (polysaccharides) from microalga Euglena gracilis using food waste hydrolysate and cell immobilisation cultivation was assessed. Synthetic medium supplemented with food waste hydrolysate proved to be a feasible option and achieved the paramylon productivity of 1.46 g/L/day in the heterotrophic (HT) cultivation. In addition, waste-based supporting materials were investigated for cell immobilisation cultivation, and waste sponge demonstrating good cell viability and paramylon productivity with maximum of 2.22 g/L/day was achieved using the synthetic medium in HT condition. However, sugarcane bagasse was not suitable for E. gracilis immobilisation as it induced serious cell lysis and oxidative stress under heterotrophic cultivation. The subsequent utilisation of the hydrolysate-based medium coupled with waste-based cell immobilisation cultivation resulted in the paramylon productivity of 1.77 g/L/day, demonstrating a promising fermentation strategy for sustainable and efficient paramylon production. This study serves as a noteworthy example of producing microalgal metabolites from the food waste hydrolysate using waste-based cell immobilisation technique. Overall, our findings provide valuable insights into green and sustainable production of microalgal biorefineries, and contributes to the advancement of the circular bioeconomy. [ABSTRACT FROM AUTHOR]

Magnetosonic (MS) waves are generally considered as electromagnetic harmonic fluctuations below the lower hybrid frequency. Here we present a correlated observation of proton ring‐like distribution and low harmonic magnetosonic waves with undetectable magnetic components (called QEMS). We conduct fully thermal simulations (WHAMP) to investigate the wave properties. The calculated growth rates can reproduce the observed spectral characteristics and demonstrate that the QEMS waves are excited as ion Bernstein modes by proton ring‐like distribution. The ratios between the wave electric and magnetic amplitudes E/B given by WHAMP indicate that the magnetic spectral densities are below the instrument noise level, and the ratios are ∼7–80 times larger than the wave phase speeds Vph, suggesting that the QEMS waves are essentially quasi‐electrostatic, not just visually quasi‐electrostatic due to the measurement limit. This study provides further insights into the QEMS natures. Plain Language Summary: Magnetosonic waves play a significant role in the magnetospheric dynamics. They usually manifest as harmonically structured electromagnetic emissions with frequencies lower than the lower hybrid frequency. Here we present a representative event of seldom reported low harmonic quasi‐electrostatic magnetosonic (QEMS) waves, which are invisible in the measured magnetic field spectra and occur together with proton ring‐like distribution. We conduct fully thermal simulations of ion Bernstein instability to investigate these waves. The calculated growth rates can well address the wave spectral characteristics and suggest that the proton ring‐like distribution is the energies source for the wave excitation. The QEMS waves may still have electromagnetic nature because the wave magnetic field may still exist but is below the instrument noise, which is true by a theoretical estimation using the measured electric field and theoretical E/B ratio. Thus, to justify the electrostatic nature, we compare E/B ratios with wave phase speed and find that E/B ratios are indeed much greater than the wave phase speed. This testifies the electrostatic nature of the QEMS waves. Our study can improve our understanding of QEMS waves. Key Points: Correlated observations of low harmonic quasi‐electrostatic magnetosonic (QEMS) waves and proton ring‐like distribution are reportedFully thermal simulations indicate that the QEMS waves are excited by the proton ring‐like distribution as ion Bernstein modesTheoretical analysis shows QEMS waves have QE nature instead of appearing as QE waves due to instrument limit [ABSTRACT FROM AUTHOR]

Sustainable development has increasingly become a primary concern of governments in the stage of high-quality economic development. Taking as an example Guangdong Province, China, where development and polarization coexist, this study uses a Vector Autoregressive(VAR) model to examine the relationship between higher education, technological innovation, and economic growth, and then uses the Coupling Coordination (CC) model to evaluate the developing coordination of subsystems where the above three elements are located; furthermore, it summarizes the mechanisms and corresponding paths of higher education on the quantity and quality of economic growth and illustrates the interactive relationships, the dynamic mechanisms, and the influencing factors. The results show that there is a dynamic interaction mechanism between higher education, technological innovation, and regional economy. The effect of this mechanism is enhanced in developed areas and with an obvious circle cumulative effect, while partly inhibited in undeveloped areas and with less or no circle cumulative effect. Therefore, on the path towards high-quality development, endogenous development models should be formulated and strengthened by developing higher education and constructing an innovation system, especially in the undeveloped areas. Higher education should be more in the regional development framework and targeted at the interaction and synergy in the regional socioeconomic system. [ABSTRACT FROM AUTHOR]

Transition metal oxides are promising electrocatalysts for water oxidation, i.e., the oxygen evolution reaction (OER), which is critical in electrochemical production of non-fossil fuels. The involvement of oxidation state changes of the metal in OER electrocatalysis is increasingly recognized in the literature. Tracing these oxidation states under operation conditions could provide relevant information for performance optimization and development of durable catalysts, but further methodical developments are needed. Here, we propose a strategy to use single-energy X-ray absorption spectroscopy for monitoring metal oxidation-state changes during OER operation with millisecond time resolution. The procedure to obtain time-resolved oxidation state values, using two calibration curves, is explained in detail. We demonstrate the significance of this approach as well as possible sources of data misinterpretation. We conclude that the combination of X-ray absorption spectroscopy with electrochemical techniques allows us to investigate the kinetics of redox transitions and to distinguish the catalytic current from the redox current. Tracking of the oxidation state changes of Co ions in electrodeposited oxide films during cyclic voltammetry in neutral pH electrolyte serves as a proof of principle. [ABSTRACT FROM AUTHOR]

Objectives: To determine the potential risk factors for intraoperative periprosthetic femoral fractures in patients with developmental dysplasia of the hip (DDH) undergoing total hip arthroplasty (THA). Methods: This was a retrospective study. Patients who were diagnosed with DDH and undergoing THA (by artificial joint replacement) at our hospital from January 1999 to December 2019 were included in this study. Clinical and radiological factors were obtained from their medical records, such as age, sex, Crowe classification, morphological features of proximal femur, and features of surgical procedure. The outcome of interest was the occurrence of intraoperative periprosthetic femoral fracture, which was recorded and classified according to the Vancouver classification system. According to the fracture status, the patients were divided into two groups: the fracture group and the non‐fracture group. Multivariate logistic regression model was built to identify the risk factors for these fractures. Results: A total of 1252 hips were finally included. Intraoperative periprosthetic femoral fractures were identified in 62 hips. The incidence of intraoperative periprosthetic femoral fractures in patients with DDH undergoing THA was 4.95%. There were 22 patients (proportion = 35.48%, incidence = 1.76%) with Type A fractures, 38 (proportion = 61.29%, incidence = 3.04%) with Type B fractures, and two (proportion = 3.23%, incidence = 0.16%) with Type C fractures. Six independent risk factors for intraoperative periprosthetic femoral fractures were identified: osteoporosis (OR = 3.434; 95% CI, 1.963–6.007), previous surgical history (OR = 4.797; 95% CI, 2.446–9.410), Dorr Type A canal (OR = 3.025; 95% CI, 1.594–5.738), retained femoral neck length (OR = 1.121; 95% CI, 1.043–1.204), implanted metaphyseal‐diaphyseal fixation stems (OR = 3.208; 95% CI, 1.562–6.591), and implanted stem with anteversion design (OR = 2.916; 95% CI, 1.473–5.770). Conclusions: The overall incidence of intraoperative periprosthetic femoral fractures in patients with DDH undergoing THA was 4.95%, which was at a moderate level compared to patients with other diseases undergoing THA. Six independent risk factors were identified: osteoporosis, previous surgical history, Dorr Type A canal, insufficient neck osteotomy level, implantation of metaphyseal‐diaphyseal fixation stem, and implantation of a stem with an anteversion design. Comprehending these risk factors might help surgeons prevent the occurrence of these intraoperative periprosthetic femoral fractures in patients with DDH. [ABSTRACT FROM AUTHOR]

Background: Corydalis saxicola Bunting, affiliated with the Papaveraceae Juss., has been proven to work well in anti-inflammation, hemostasis, and analgesia. This study was designed to observe the effect and potential mechanism of Corydalis saxicola Bunting total alkaloids (CSBTA) on paclitaxel-induced peripheral neuropathy (PIPN). Materials and methods: Rats were injected 2 mg/kg paclitaxel 4 times and administrated with 30 or 120 mg/kg CSBTA. Mechanical and thermal allodynia and hyperalgesia were tested. After 40 days, serum was collected to detect PGE2, TNF-α, and IL-1β by ELISA. The L4-L6 segment spinal cord, DRG, and plantar skin were harvested, and Western-blot or RT-qPCR analyzed protein and gene levels of pro-inflammatory cytokines, p38 MAPK, PKCε, and TRPV1. The PIPN cell model was established with paclitaxel (300 nM, 5 d) in primary DRG neurons. We examined the effect of CSBTA (25 μg/ml or 50 μg/ml) by measuring the mRNA levels in PGE2, TNF-α and CGRP, and the protein expression on the PKCε/p38 MAPK/TRPV1 signaling pathway in the PIPN cell model. Results: The results showed that CSBTA effectively ameliorated allodynia and hyperalgesia, and regulated cytokines' contents (PGE2, TNF-α, and IL-1β) and neuropeptides (CGRP and SP) in different tissues in vivo. In addition, CSBTA significantly decreased cytokine gene levels of DRG neurons (PGE2, TNF-α, and CGRP) and the protein expressions of PKCε/p38 MAPK/TRPV1 signaling pathway in vivo and in vitro. Conclusion: Therefore, CSBTA has a perspective therapeutic effect on the treatment of paclitaxel-induced peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Over 100 kinds of proteins are expressed as glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) on the cell surface in mammalian cells. GPI-APs possess unique properties in terms of their intracellular trafficking and association with lipid rafts. Although it is clear that GPI-APs play critical roles in various biological phenomena, it is poorly understood how the GPI moiety contributes to these mechanisms. More than 30 genes are involved in the correct biosynthesis of GPI-APs. We here constructed a cell library in which 32 genes involved in GPI biosynthesis were knocked out in human embryonic kidney 293 cells. Using the cell library, the surface expression and sensitivity to phosphatidylinositol-specific phospholipase C of GPI-APs were analyzed. Furthermore, we identified structural motifs of GPIs that are recognized by a GPI-binding toxin, aerolysin. The cell-based GPI-knockout library could be applied not only to basic researches, but also to applications and methodologies related to GPI-APs. Liu et al. construct a knock out cell library of genes involved in the biosynthesis of glycosylphosphatidylinositol (GPI)-anchored protein (GPI-APs) from HEK-293 cells and analyzed the surface expression and sensitivity to phosphatidylinositol-specific phospholipase C. Furthermore, the authors also identify structural motifs of GPIs that are recognized by a GPI-binding toxin, aerolysin. [ABSTRACT FROM AUTHOR]

Background: Considering the high morbidity and mortality of lung cancer and the high incidence of pulmonary nodules, clearly distinguishing benign from malignant lung nodules at an early stage is of great significance. However, determining the kind of lung nodule which is more prone to lung cancer remains a problem worldwide. Methods: A total of 480 patients with pulmonary nodule data were collected from Shandong, China. We assessed the clinical characteristics and computed tomography (CT) imaging features among pulmonary nodules in patients who had undergone video‐assisted thoracoscopic surgery (VATS) lobectomy from 2013 to 2018. Preliminary selection of features was based on a statistical analysis using SPSS. We used WEKA to assess the machine learning models using its multiple algorithms and selected the best decision tree model using its optimization algorithm. Results: The combination of decision tree and logistics regression optimized the decision tree without affecting its AUC. The decision tree structure showed that lobulation was the most important feature, followed by spiculation, vessel convergence sign, nodule type, satellite nodule, nodule size and age of patient. Conclusions: Our study shows that decision tree analyses can be applied to screen individuals for early lung cancer with CT. Our decision tree provides a new way to help clinicians establish a logical diagnosis by a stepwise progression method, but still needs to be validated for prospective trials in a larger patient population. [ABSTRACT FROM AUTHOR]

Auroral kilometric radiations (AKR) are strong radio emission phenomena, and can produce significant acceleration or scattering of radiation belt electrons. The variation of AKR wave amplitude with the latitude (λ) has not been reported so far owing to lack of measurements. Here, using observations of the Arase satellite and Van Allen Probes from March 23, 2017 to July 31, 2019, we present the first statistical study on the AKR electric field amplitude (Et) in the radiation belts for |λ| = 0° − 40° and L‐shell L = 3.0–6.2. Results (totally 14,770 samples) show that Et can be described by a concise formula: Et(λ) = E0 exp(ξ sin |λ|), decreasing with decreasing latitude. Fitting parameters E0 and ξ are limited in the ranges: E0 = 0.054–0.340 mV/m and ξ = 3.0–4.2. Wave amplitudes are greater (smaller) under intense (weak) geomagnetic conditions. This study helps to better quantify the gyroresonance between AKR and radiation belt electrons. Plain Language Summary: Auroral kilometric radiation (AKR) is a strong radio emission phenomenon which is generated in the low density polar cavity. They can propagate downward into radiation belts and produce significant acceleration or pitch angle scattering of energetic electrons. Those electrons can yield serious damage to spacecraft or ozone destruction. Because wave‐particle interaction generally occurs at each point along the field line and diffusion coefficients are directly proportional to the square of wave amplitude, it is necessary to specify the field‐aligned wave amplitude. However, previous calculations of AKR‐electron interaction were based on the assumption of the constant field‐aligned wave amplitude. Here, using observations of the Arase satellite and Van Allen Probes from March 23, 2017 to July 31, 2019, we report a field‐aligned distribution of AKR wave amplitude for the first time. Gaussian fitting for the electric field power spectral density is performed to obtain the wave amplitude of each AKR sample. We calculate averaged wave amplitudes of total 14,770 samples on the dayside and nightside. Results show that wave amplitude can be described by a concise formula, decreasing obviously with decreasing latitude. Wave amplitudes are greater (smaller) under intense (weak) geomagnetic condition. This paper provides the further understanding of AKR‐electron interaction. Key Points: The field‐aligned distribution of AKR wave amplitude is presented for the first time based on Arase satellite and Van Allen ProbesWave amplitudes can be approximately described by a concise exponential formula and decrease obviously with decreasing latitudeThe AKR sample and amplitude are roughly symmetric around the equator, wave amplitudes increase with increasing geomagnetic activities [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid (LPA) and its G-protein-coupled receptors (Lpar1–Lpar6) mediate a plethora of activities associated with cancer growth and progression. However, there is no systematic study about whether and how LPA promotes esophageal squamous cell carcinoma (ESCC). Here, we show that autotaxin (ATX), a primary LPA-producing enzyme, is highly expressed in ESCC, and overexpressed ATX is associated with the poor outcome of ESCC patients. Meanwhile, the expression of Lpar1 was much higher in ESCC cells compared with Het-1a (human esophagus normal epithelial cells). Functional experiments showed that LPA remarkably increased the proliferation and migration of ESCC cells. Furthermore, Lpar1 knockdown abolished the effect of LPA on ESCC cell proliferation and migration. Mechanistic studies revealed that LPA promoted ESCC cell lines proliferation and migration through PI3K/Akt pathway. Treatment of KYSE30 cell xenografts with Lpar1 inhibitor BMS-986020 significantly repressed tumor growth. Our results shed light on the important role of LPA in ESCC, and Lpar1 might be a potential treatment target for ESCC. [ABSTRACT FROM AUTHOR]

[Display omitted] • 12 new oligomeric phloroglucinols were isolated from tropic Rhodomyrtus tomentosa. • An enantiomeric mixture of 3a and 3b is an excellent h AChE inhibitor with an IC 50 value of 1.21 μM. • Molecular docking was used to uncover the possible mechanism of 3a and 3b with h AChE. • The racemic mixture of 3a and 3b showed the most anti-MRSA activity with MIC and MBC values of 0.50 μg/mL. • The SEM studies revealed that 3a and 3b could destroy the biofilm structures of MRSA. Alzheimer's diseases (AD) and other infectious diseases caused by drug-resistance bacteria have posed a serious threat to human lives and global health. With the aim to search for human acetylcholinesterase (h AChE) inhibitors and antibacterial agents from medicinal plants, 16 phloroglucinol oligomers, including two new phloroglucinol monomers (1a and 1b), four new phloroglucinol dimers (3a , 3b , 4b , and 5a), six new phloroglucinol trimers (6a , 6b , 7a , 7b , 8a , and 8b), and two naturally occurring phloroglucinol monomers (2a and 2b), along with two known congeners (4a and 5b), were purified from the leaves of tropic Rhodomyrtus tomentosa. The structures and absolute configurations of these new isolates were unequivocally established by comprehensive analyses of their spectroscopic data (NMR and HRESIMS), ECD calculation, and single crystal X-ray diffraction. Structurally, 3a / 3b shared a rare C-5 ′ formyl group, whereas 6a / 6b possessed a unique C-7 ′ aromatic ring. In addition, 7a / 7b and 8a / 8b were rare phloroglucinol trimers with a bis-furan and a C-6 ′ hemiketal group. Pharmacologically, the mixture of 3a and 3b showed the most potent human acetylcholinesterase (h AChE) inhibitory activity with an IC 50 value of 1.21 ± 0.16 μM. The molecular docking studies of 3a and 3b in the h AChE binding sites were performed, displaying good agreement with the in vitro inhibitory effects. In addition, the mixture of 3a and 3b displayed the most significant anti-MRSA (methicillin-resistant Staphylococcus aureus) with MIC and MBC values of both 0.50 μg/mL, and scanning electron microscope (SEM) studies revealed that they could destroy the biofilm structures of MRSA. The findings provide potential candidates for the further development of anti-AD and anti-bacterial agents. [ABSTRACT FROM AUTHOR]

Steel members using nonsymmetric sections are envisioned as popular because of the advancement in manufacturing techniques, in which frame analysis method under extreme scenarios, such as fire hazards, has not been thoroughly established. The element formulation for those members has been commonly derived based on either the updated-Lagrangian (UL) or the total-Lagrangian (TL) methods. However, the UL method is difficult to analyze the steel member exposed to fires because the previous equilibrium conditions may be destroyed due to the material stiffness degradation at elevated temperatures. Nevertheless, the TL method can be used for studying steel members under fire, but it is inefficient, time-consuming, and requires starting-over computation at every temperature increment. To this, the co-rotational (CR) method could be a promising solution for tackling the analysis problems of steel members in fire efficiently and accurately. The CR method separately describes the element and its rigid body movements, such that the material stiffness degradation can be considered at the element level without the starting-over computation at new temperature increments, which is numerically efficient. This paper reformulates the beam-column element formulation with the warping degree of freedom for nonsymmetric section members using the CR method, which can conveniently consider the material degradation and the thermal expansion for the analysis of steel members at elevated temperatures. The lateral-torsional and flexural-torsional buckling of nonsymmetric section members can be captured robustly. Detailed derivation for element formulation is given, and several examples are provided for verifying the accuracy and examining the robustness of the proposed method. • Large deflection analysis of steel structures at elevated temperatures is studied. • The Wagner effects of the members with nonsymmetric sections are considered. • A beam-column element is proposed based on the co-rotational method. • Secant relations are derived to calculate the element reaction forces. • A Newton-Raphson-typed numerical procedure for the numerical analysis is proposed. [ABSTRACT FROM AUTHOR]

The deteriorated plasticity arising from the insoluble precipitates may lead to cracks during the rolling of FeCrAl alloys. The microstructure evolution and hot deformation behavior of an FeCrAl alloy were investigated in the temperature range of 750–1200 °C and strain rate range of 0.01–10 s−1. The flow stress of the FeCrAl alloy decreased with an increasing deformation temperature and decreased strain rate during hot working. The thermal deformation activation energy was determined to be 329.49 kJ/mol based on the compression test. Then, the optimal hot working range was given based on the established hot processing maps. The hot processing map revealed four small instability zones. The optimal working range for the material was identified as follows: at a true strain of 0.69, the deformation temperature should be 1050–1200 °C, and the strain rate should be 0.01–0.4 s−1. The observation of key samples of thermally simulated compression showed that discontinuous dynamic recrystallization started to occur with the temperate above 1000 °C, leading to bended grain boundaries. When the temperature was increased to 1150 °C, the dynamic recrystallization resulted in a microstructure composed of fine and equiaxed grains. [ABSTRACT FROM AUTHOR]