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Basophils are a rare type of granulocyte in peripheral blood. Owing to their accessibility in circulation and similarities to mast cells, basophils were considered a tool to gain insight into the function of mast cells. However, recent studies have uncovered that basophils have unique biology, specifically in activation, recruitment, and potential biomarkers. Accordingly, some previously unrecognized functions, particularly in neuroimmunology, have been found, suggesting a role of basophils in inflammatory and pruritic disorders. In this review, we aim to present an overview of basophil biology to show how basophils contribute to certain pruritic skin diseases.

Background: S1P (sphingosine-1-phosphate) has been reported to possess vasodilatory properties, but the underlying pathways are largely unknown. Methods: Isolated mouse mesenteric artery and endothelial cell models were used to determine S1P-induced vasodilation, intracellular calcium, membrane potentials, and calcium-activated potassium channels (K Ca 2.3 and K Ca 3.1 [endothelial small- and intermediate-conductance calcium-activated potassium channels]). Effect of deletion of endothelial S1PR1 (type 1 S1P receptor) on vasodilation and blood pressure was evaluated. Results: Mesenteric arteries subjected to acute S1P stimulation displayed a dose-dependent vasodilation response, which was attenuated by blocking endothelial K Ca 2.3 or K Ca 3.1 channels. In cultured human umbilical vein endothelial cells, S1P stimulated immediate membrane potential hyperpolarization following activation of K Ca 2.3/K Ca 3.1 with elevated cytosolic Ca 2+ . Further, chronic S1P stimulation enhanced expression of K Ca 2.3 and K Ca 3.1 in human umbilical vein endothelial cells in dose- and time-dependent manners, which was abolished by disrupting either S1PR1-Ca 2+ signaling or downstream Ca 2+ -activated calcineurin/NFAT (nuclear factor of activated T-cells) signaling. By combination of bioinformatics-based binding site prediction and chromatin immunoprecipitation assay, we revealed in human umbilical vein endothelial cells that chronic activation of S1P/S1PR1 promoted NFATc2 nuclear translocation and binding to promoter regions of K Ca 2.3 and K Ca 3.1 genes thus to upregulate transcription of these channels. Deletion of endothelial S1PR1 reduced expression of K Ca 2.3 and K Ca 3.1 in mesenteric arteries and exacerbated hypertension in mice with angiotensin II infusion. Conclusions: This study provides evidence for the mechanistic role of K Ca 2.3/K Ca 3.1-activated endothelium-dependent hyperpolarization in vasodilation and blood pressure homeostasis in response to S1P. This mechanistic demonstration would facilitate the development of new therapies for cardiovascular diseases associated with hypertension.

As a prominent component of turbidite deposition systems, turbidite lobe internal architecture characterization has proven essential due to its complicated sedimentary hierarchy and evident heterogeneity. This paper demonstrates an integrated methodology for doing a multiple-point stochastic (MPS) simulation of deepwater turbidite single-lobe architecture. Based on the logging data, high-frequency seismic data, thorough architectural feature analysis, and 3D training image, MPS-based geologic modeling of the Miocene turbidite lobe reservoir in the Lower Congo Basin is carried out. This effort has two objectives: (1) to expand the geologic knowledge base of deepwater turbidite lobes with morphology parameters and (2) to develop a process of turbidite geomodeling that could characterize the architectural hierarchy of a single lobe with limited difficult data. As a first step, we analyze and characterize properties of the single-lobe element characteristics and the manner of sedimentary dispersion using 145 m long cores, well logging, and seismic analysis. Second, shallow seismic-based turbidite lobes pick-up and morphology parameter measurements have been conducted to collect quantitative characteristics of turbidite lobe and will be used as geomodeling guidance. Third, a 3D lobe complex training image with single-lobe architecture elements superposition is derived by a seismic geobody caving (using threshold truncation) and enhanced based on the sedimentary distribution mode. An MPS simulation incorporating well data, morphological parameters, training image, and seismic inversion constraint is then performed, which results in obtaining an architecture model that could describe a single lobe. The simulation results generally followed the lobe architecture elements morphology and superposition. The coincidence between the MPS simulated turbidites lobe complex architecture model and the posterior well could reach up to 86%. The paper gives the methodology for a case study that proved the implementation of single turbidite lobe architectural characterization using an MPS, and the recommended process could be applied to other fields.

Background: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. Summary: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. Key Messages: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

The autonomous reacquisition of laser links between distributed spacecraft is the fundamental technique in missions to detect gravitational waves in space. It involves rapidly maneuvering three spacecraft’s attitudes to adjust their laser beams so that they can cover one another within regions of uncertainty that arise owing to various spatial disturbances and system errors. This paper develops a methodology within the framework of convex optimization to optimize the reacquisition procedure on board and to reduce the duration of reacquisition, and therefore the region of uncertainty changing over the temporal history. A sampling-based method of modeling is first developed to remodel the problem of reacquisition as an equivalent problem of convex optimization with additional minimum-function constraints. An approach to penalization relaxation is then presented to convexify the minimum-function constraint and significantly improve the convergence of the algorithm by overcoming the drawbacks of potential artificial infeasibility, zero-gradient singularity, and solution-chattering situations. Finally, a detailed characterization of task uncertainty is considered to improve the applicability of the proposed method. Numerical comparisons between the proposed method and the most relevant techniques researched in recent studies are provided under multiple, randomly generated simulation environments to demonstrate its efficiency, universality, and robustness.

Breast cancer is considered as the most prevalent cancer. Using ultrasound images is a momentous clinical diagnosis method to locate breast tumors. However, accurate segmentation of breast tumors remains an open problem due to ultrasound artifacts, low contrast, and complicated tumor shapes in ultrasound images. To address this issue, we proposed a boundary-oriented network (BO-Net) for boosting breast tumor segmentation in ultrasound images. The BO-Net boosts tumor segmentation performance from two perspectives. Firstly, a boundary-oriented module (BOM) was designed to capture the weak boundaries of breast tumors by learning additional breast tumor boundary maps. Second, we focus on enhanced feature extraction, which takes advantage of the Atrous Spatial Pyramid Pooling (ASPP) module and Squeeze-and-Excitation (SE) block to obtain multi-scale and efficient feature information. We evaluate our network on two public datasets: Dataset B and BUSI. For the Dataset B, our network achieves 0.8685 in Dice, 0.7846 in Jaccard, 0.8604 in Precision, 0.9078 in Recall, and 0.9928 in Specificity. For the BUSI dataset, our network achieves 0.7954 in Dice, 0.7033 in Jaccard, 0.8275 in Precision, 0.8251 in Recall, and 0.9814 in Specificity. Experimental results show that BO-Net outperforms the state-of-the-art segmentation methods for breast tumor segmentation in ultrasound images. It demonstrates that focusing on boundary and feature enhancement creates more efficient and robust breast tumor segmentation.

According to the survey data, the annual death toll due to traffic accidents in the world reaches 1.25 million, in China is as high as 104,000, ranking first in the world. In the death rate of traffic accidents, more than 60% are caused by early warning or rescue in time. At present, there are many problems in China's traffic accident emergency rescue, such as low efficiency, rescue in time. According to the demand of smart city construction, the traditional emergency rescue mode of traffic accident is facing transformation. The rapid popularity of tachograph in recent years can be seen that car owners' awareness of safe driving is strengthening. However, the functions of the traditional tachograph are mostly limited to being the evidence carrier of traffic disputes. The latest multifunctional recorder on the market also aims to improve user experience, increase intelligent voice, navigation and other functions, and has not been applied in traffic accident emergency rescue.

Overexpression of androgen receptor (AR) is the primary cause of castration-resistant prostate cancer, although mechanisms upregulating AR transcription in this context are not well understood. Our RNA-seq studies revealed that SMAD3 knockdown decreased levels of AR and AR target genes, whereas SMAD4 or SMAD2 knockdown had little or no effect. ChIP-seq analysis showed that SMAD3 knockdown decreased global binding of AR to chromatin. Mechanistically, we show that SMAD3 binds to intron 3 of the AR gene to promote AR expression. Targeting these binding sites by CRISPRi reduced transcript levels of AR and AR targets. In addition, ∼50% of AR and SMAD3 ChIP-seq peaks overlapped, and SMAD3 may also cooperate with or co-activate AR for AR target expression. Functionally, AR re-expression in SMAD3-knockdown cells partially rescued AR target expression and cell growth defects. The SMAD3 peak in AR intron 3 overlapped with H3K27ac ChIP-seq and ATAC-seq peaks in datasets of prostate cancer. AR and SMAD3 mRNAs were upregulated in datasets of metastatic prostate cancer and CRPC compared with primary prostate cancer. A SMAD3 PROTAC inhibitor reduced levels of AR, AR-V7 and AR targets in prostate cancer cells. This study suggests that SMAD3 could be targeted to inhibit AR in prostate cancer.

The purpose of this study was to explore the relationship among unmet care needs, social support, and anxiety in patients with lung transplantation. We conducted a cross-sectional study; 173 lung transplant patients who met the inclusion criteria completed questionnaires including the Organ Transplant Recipient Care Needs Scale, the Perceived Social Support Scale, and the Anxiety Self-Rating Inventory. Pearson’s correlations and multiple linear regression analyses were used to test the relationship between the selected variables. The results showed a moderate level of unmet care needs at home for lung transplant patients. Education level, transplant-related complications, perceived social support, and anxiety were significantly correlated with unmet care needs of lung transplant patients at home ( p < .05), explaining 23.8% of the total variance for unmet care needs. Further research is required to explore interventions to reduce the level of unmet care needs of lung transplant patients.

Mesenchymal stem cell-derived extracellular vesicles (MSCs-EVs) possess cardioprotection in acute myocardial infarction. Nevertheless, the therapeutic intervention potential and the molecular mechanism of EVs from NMN (Nicotinamide mononucleotide) preconditioned hUCMSCs (N-EVs) in acute myocardial infarction remains unknown. In the present study, EVs from hUCMSCs (M-EVs) and N-EVs were identified by electron microscopy, immunoblotting and nanoparticle tracking analysis. Compared with M-EVs, N-EVs significantly increased the proliferation, migration, and angiogenesis of HUVECs. Meanwhile, N-EVs markedly reduced apoptosis and cardiac fibrosis and promoted angiogenesis in the peri-infarct region in the MI rats. A high-throughput miRNA sequencing and qPCR methods analysis revealed that miR-210-3p was abundant in N-EVs and the expression of miR-210-3p was obviously upregulated in HUVECs after N-EVs treated. Overexpression of miR-210-3p in HUVECs significantly enhanced the tube formation, migration and proliferative capacities of HUVECs. However, downregulation of miR-210-3p in HUVECs markedly decreased the tube formation, migration and proliferative capacities of HUVECs. Furthermore, bioinformatics analysis and luciferase assays revealed that EphrinA3 (EFNA3) was a direct target of miR-210-3p. Knockdown of miR-210-3p in N-EVs significantly impaired its ability to protect the heart after myocardial infarction. Altogether, these results indicated that N-EVs promoted the infarct healing through improvement of angiogenesis by miR-210-3p via targeting the EFNA3. Graphical Abstract Created with Biorender.com.

We previously found that Wuzhuyu Decoction (WZYD) could affect central and peripheral 5-HT to relieve hyperalgesia in chronic migraine (CM) model rats, possibly related to gut microbiota. However, the exact role of gut microbiota has not been elucidated. Accumulating evidence points to the possibility of treating central nervous system disease via the gut-brain axis. In our study, the inflammatory soup-induced CM model rats presented depression- and anxiety-like behaviors which both related to insufficient 5-HT. It was found that antibiotic administration caused community dysbiosis, and proteobacteria became the main dominant bacteria. The bacteria related to short-chain fatty acids and 5-HT generation were reduced, resulting in reduced levels of 5-HT, tryptophan hydroxylase, and secondary bile acids. Functional prediction-revealed sphingolipid signaling pathway in CM rats was significantly decreased and elevated after WZYD treatment. The effect of WZYD could be weakened by antibiotics. The CM rats exhibited anxiety- and depression-like behavior with 5-HT and number of neurons decreased in the CA1 and CA2 regions of hippocampal. The treatment of WZYD could recover to varying degrees. Antibiotics combined with WZYD attenuate the effect of WZYD on increasing the 5-HT content and related protein expression in the brain stem, plasma and colon, reducing CGRP, c-Fos, and inflammatory factors. And antibiotics also led to colon length increasing and stool retention, so that the antimigraine effect was weakened compared with WZYD. This experiment revealed that gut microbiota mediated WZYD treatment of CM rats with anxiety-depression like behavior.

Transformed small-cell lung cancer (T-SCLC) has an extremely poor prognosis, and no remedies based on immunotherapy have been evaluated among T-SCLC patients. We retrospectively analysed the efficacy and safety of combining atezolizumab with chemotherapy for T-SCLC.Forty-seven patients harbouring EGFR mutations who developed T-SCLC were enrolled. Eleven patients who used immunotherapy were defined as the I/O group, and the remaining 36 were defined as the Non-I/O group. Clinical characteristics, pathological data, and survival outcomes were collected. RNA sequencing and whole-exome sequencing (WES) were performed for in-depth analysis.All patients received at least one line of EGFR-TKI before rebiopsy to confirm T-SCLC. Nine patients received atezolizumab-bevacizumab-carboplatin-paclitaxel (albumin-bound) (ABCP), and the remaining 2 received atezolizumab-etoposide-carboplatin (ECT) in the I/O group. The objective response rate was 73 % (8/11). The median progression-free survival (mPFS) of T-SCLC on post-transformation therapy with I/O group and Non-I/O group was 5.1 m and 4.1 m, respectively. The median post-T-SCLC overall survival of the I/O group was significantly longer than that Non-I/O group (20.2 m vs 7.9 m, P ＜ 0.01). T-SCLC harbouring EGFR L858R tended to be longer than EGFR 19del (mPFS: not reached vs 3.7 m, P = 0.11). Positive PD-L1 status was also associated with PFS benefits (mPFS: 6.0 m vs 3.7 m, P = 0.20). Furthermore, RNA sequencing revealed that expression of SFTPA1 is significantly higher in the durable clinical benefit group. WES showed that STC2 mutation is more frequently observed at the time-point immunotherapy acquired resistance. Combination therapy based on a PD-L1 inhibitor was well tolerated, and the safety profile was consistent with previously reported studies.Our study first demonstrated that a PD-L1 inhibitor combined with chemotherapy ± bevacizumab could be a potential safe option for specific SCLC-transformed patients. Subsequent studies with more patients are essential to verify the efficacy and potential biomarkers.

In this work, the study of the kinetics of the transformation of methanol to aromatics was conducted over a 3Zn-3Si/ZSM-5 catalyst for the high selectivity of p-xylene.

The rGO/NC interface, as a protective barrier, can effectively prevent the aggregation of Ru atoms during the repreparation process and promote the NRR process.