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Identification of B-cell epitopes (BCEs) plays an essential role in the development of peptide vaccines, immuno-diagnostic reagents, and antibody design and production. In this work, we generated a large benchmark dataset comprising 126,779 experimentally-supported, linear epitope-containing regions in 3567 protein clusters from over 1.3 million B cell assays. Analysis of this curated dataset showed large pathogen diversity covering 176 different families. The accuracy in linear BCE prediction was found to strongly vary with different features, while the performance by sequence features was superior to that by structural features. To search more efficient and interpretive feature representations, a ten-layer deep learning framework for linear BCE prediction, namely NetBCE, was developed. NetBCE achieved high accuracy and robust performance with the average area under the curve (AUC) value of 0.846 in five-fold cross validation through automatically learning the informative classification features. NetBCE substantially outperformed the conventional machine learning algorithms and other tools, with an over 22.06% improvement of AUC value compared to other tools using an independent dataset. Through investigating the output of important network modules in NetBCE, epitopes and non-epitopes tended to present in distinct regions with efficient feature representation along the network layer hierarchy. The NetBCE tool will be useful for linear B-cell epitopes identification and more generally, immunological and computational biology research.

The frictional properties of a uniaxial tensile strained graphene interface are studied using molecular dynamics simulations. A misfit interval statistical method (MISM) is applied to characterize the atomistic misfits at the interface and strain soliton pattern. During sliding along both armchair and zigzag directions, the lateral force depends on the ratio of graphene flake length (

Background: Calcium (Ca 2+ ) is a key regulator of energy metabolism. Impaired Ca 2+ homeostasis damages mitochondria, causing cardiomyocyte death, pathological hypertrophy, and heart failure. This study investigates the regulation and the role of the mitochondrial Ca 2+ uniporter (MCU) in chronic stress-induced pathological cardiac remodeling. Methods: MCU knockout or transgenic mice were infused with isoproterenol (ISO; 10 mg/kg per day, 4 weeks). Cardiac hypertrophy and remodeling were evaluated by echocardiography and histology. Primary cultured rodent adult cardiomyocytes were treated with ISO (1 nmol/L, 48 hours). Intracellular Ca 2+ handling and cell death pathways were monitored. Adenovirus-mediated gene manipulations were used in vitro. Results: Chronic administration of the β-adrenergic receptor agonist ISO increased the levels of the MCU and the MCU complex in cardiac mitochondria, raising mitochondrial Ca 2+ concentrations, in vivo and in vitro. ISO also upregulated MCU without affecting its regulatory proteins in adult cardiomyocytes. It is interesting that ISO-induced cardiac hypertrophy, fibrosis, contractile dysfunction, and cardiomyocyte death were exacerbated in global MCU knockout mice. Cardiomyocytes from knockout mice or overexpressing a dominant negative MCU exhibited defective intracellular Ca 2+ handling and activation of multiple cell death pathways. Conversely, cardiac-specific overexpression of MCU maintained intracellular Ca 2+ homeostasis and contractility, suppressed cell death, and prevented ISO-induced heart hypertrophy. ISO upregulated MCU expression through activation of Ca 2+ /calmodulin kinase II δB (CaMKIIδB) and promotion of its nuclear translocation via calcineurin-mediated dephosphorylation at serine 332. Nuclear CaMKIIδB phosphorylated CREB (cAMP-response element binding protein), which bound the Mcu promoter to enhance Mcu gene transcription. Conclusions: The β-adrenergic receptor/CaMKIIδB/CREB pathway upregulates Mcu gene expression in the heart. MCU upregulation is a compensatory mechanism that counteracts stress-induced pathological cardiac remodeling by preserving Ca 2+ homeostasis and cardiomyocyte viability.

In wound treatment, severe bleeding and infection are always primary challenges. Therefore, it is highly desired to develop novel dressing with both hemostatic and antibacterial capability. Herein, a series of biocomposite hemostatic films (BHFs) based alginate/chitosan/collagen-berberine have been prepared and well characterized for further biofunctional study. We have demonstrated that the hemostatic and antibacterial activities were significantly enhanced by calcium/berberine dual-crosslinking system in the film. Through the synergistic effects, BHF-6B exhibited a shorter in vivo clotting and wound healing time than that of commercial dressing in rat tail amputation and full-thickness skin defect models. Additionally, BHF-6B showed excellent bacteriostatic activity with long-term effects. Moreover, hemolysis and cytotoxicity tests in vitro illustrated the prominent biocompatibility of the composite films. Notably, BHF-6B could be degraded quickly and completely in vivo. Overall, the present work indicated that the functionalized BHF-6B has great potential as an absorbable biomaterial for wound treatment.

Context.—Salivary gland-type tumors (SGTs) of the lung represent a distinct group of lung neoplasms. Pulmonary SGTs often pose diagnostic challenges, especially in small biopsy and cytology samples because of limited sample volume and overlapping morphology among pulmonary SGTs, metastatic SGTs of head and neck origin, and other lung tumors.Objective.—To identify the clinical characteristics, histomorphology, immunophenotypic features, and molecular alterations that are crucial for the diagnosis and differential diagnosis of pulmonary SGTs, especially in small biopsy and cytology specimens.Data Sources.—Literature review and authors' personal practice experience.Conclusions.—An accurate diagnosis of pulmonary SGTs can be achieved by careful evaluation of clinical findings and histomorphology in conjunction with immunohistochemical studies and molecular analysis.

In the post-COVID-19 era, environmental pollution has been a serious threat to public health. Enterprises are in urgent need of enhancing green technology innovation as the main source of pollutant emissions, and it is necessary for governments to support green innovation of enterprises to reduce pollutant emissions and promote public health. In this context, this paper investigates whether the Ambient Air Quality Standard (AAQS) implemented in 2012 in China contributes to green innovation of enterprises, to provide implications for environmental protection and public health. By using panel data of Chinese A-share listed companies from 2008 to 2020, this study adopts the difference-in-difference model to analyze the policy impact of environmental regulation on green innovation of enterprises and its internal mechanism. The results show that AAQS has significantly improved the green innovation of enterprises. Furthermore, AAQS affects the green innovation of enterprises by virtue of two mechanism paths: compliance cost effect and innovation offset effect. On the one hand, AAQS leads to an increase in production costs of enterprises, thus inhibiting green innovation activities of enterprises. On the other hand, AAQS encourages enterprises to increase R&D investment in green technology, thus enhancing their green innovation. In addition, the impact of AAQS on firms' green innovation has heterogeneous characteristics. Our findings not only enrich the studies of environmental regulation and green innovation of enterprises but also provide policymakers in China and other developing countries with implications for environmental protection and public health improvement.

Facing the intensification of global carbon emissions and the increasingly severe pressure of environmental pollution, listed companies urgently need to promote green innovation, achieve green transformation, and alleviate environmental problems. Green finance policy has played a significant role as a financial strategy for environmental governance in affecting green innovation level over the years. In this context, taking the green finance reform and innovation pilot zone (GFRIPZ) implemented in 2017 in China as a quasi-natural experiment, this paper analyzes the impact of green finance policy on green innovation level of listed companies by the difference-in-difference model. Based on the data of Chinese A-share listed companies from 2008 to 2020, the results of empirical analysis show that green finance significantly promotes green innovation of listed companies. The effect is profound on green utility model patents, but less pronounced on green invention patents. Among all these pilot zones, the policy effects of GFRIPZ ranked in descending order are Zhejiang, Guangdong, Jiangxi, Guizhou, and Xinjiang. In addition, green finance has a more significant impact on heavy-polluting industries, large and state-owned enterprises, and listed companies located in the eastern region. Furthermore, the effects of industry heterogeneity ranked in descending order are energy, manufacturing, processing, and engineering industry, while it is not obvious in the service industry. Mechanism analysis suggests that the effect is driven by a reduction in the cost of debt financing and an increase in the long-term debt ratio. The findings provide implications for policymakers to promote the level of green innovation and environmental governance. Therefore, policymakers should support the long-term creative development of green invention patents by reducing the cost of debt financing and increasing the long-term debt ratio and consider the heterogeneous characteristics of listed companies when formulating green finance policies.

Suppression of the cardiac sodium channel NaV1.5 leads to fatal arrhythmias in ischemic heart disease (IHD). However, the transcriptional regulation of NaV1.5 in cardiac ischemia is still unclear. Our studies are aimed to investigate the expression of enhancer of zeste homolog 2 (EZH2) in IHD and regulation of cardiac NaV1.5 expression by EZH2. Human heart tissue was obtained from IHD and non-failing heart (NFH) patients; mouse heart tissue was obtained from the peri-infarct zone of hearts with myocardial infarction (MI) and hearts with a sham procedure. Protein and mRNA expression were measured by immunoblotting, immunostaining, and qRT-PCR. Protein-DNA binding and promoter activity were analyzed by ChIP-qPCR and luciferase assays, respectively. Na+ channel activity was assessed by whole-cell patch clamp recordings. EZH2 and H3K27me3 were increased while NaV1.5 expression was reduced in IHD hearts and in mouse MI hearts compared to the controls. Reduced NaV1.5 and increased EZH2 mRNA levels were observed in mouse MI hearts. A selective EZH2 inhibitor, GSK126 decreased H3K27me3 and elevated NaV1.5 in HL-1 cells. Silencing of EZH2 expression decreased H3K27me3 and increased NaV1.5 in these cells. EZH2 and H3K27me3 were enriched in the promoter regions of Scn5a and were decreased by treatment with EZH2 siRNA. GSK126 inhibited the enrichment of H3K27me3 in the Scn5a promoter and enhanced Scn5a transcriptional activity. GSK126 significantly increased Na+ channel activity. Taken together, EZH2 is increased in ischemic hearts and epigenetically suppresses Scn5a transcription by H3K27me3, leading to decreased NaV1.5 expression and Na+ channel activity underlying the pathogenesis of arrhythmias.

The miniaturization of spectrometers have attracted much attention owning to the demand for portable or in situ spectral analysis in a wide variety of fields, but it is a great challenge to push them into practical applications due to high cost, complicated configuration, and sensitivity to external disturbance. We report on a miniature Fourier transform (FT) spectrometer based on fiber-tip Fizeau interferometer. Hand pulling or any other types of force can be used to drive optical path difference (OPD) scan. Interferences are monitored as a function of time by two photodetectors, one is used to detect the whole interferogram while the other to measure single-wavelength interferogram. In this design, the instantaneous interference intensity as well as OPD can be obtained in an accurate way so that the exact spatial interferogram of the incident spectrum can be worked out. Consequently, the incident spectrum can be retrieved by FT method. A resolution of 7.69 cm−1 in the wavelength range of 1400 nm ∼ 1700 nm is achieved. Experimental results show that the performance of our device is comparable to the commercial benchtop spectrometer. Our device is independent of the complicated fabrication procedures, easy of usage, and cost effective. We envision that the proposed design will inspire a new concept for constructing simple and cheap spectrometers that is well suited for practical applications.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal neoplasm typically arising on the face of older individuals, most commonly around the eyelids. Histopathologic features include a circumscribed proliferation of low-grade epithelioid cells with areas of cystic and cribriform growth, foci of intracytoplasmic and extracellular mucin, and coexpression of endocrine, neuroendocrine, and cytokeratin markers by immunohistochemistry. Given histopathologic and immunohistochemical similarities, EMPSGC is often likened to solid papillary carcinoma of the breast and endocrine ductal carcinoma in situ, and is thought by many to represent a forme fruste of mucinous carcinoma of the skin. To date, the vast majority of reported cases of EMPSGC have been described as having indolent behavior, with no cases of distant metastasis yet reported. Here we report a unique case of EMPSGC that recurred over several years following standard surgical excision and Mohs micrographic surgery, with subsequent metastasis to the parotid gland and axial skeleton.

In this study, we investigate the effect of including ridged disk vanes on the operation of a magnetically insulated transmission line oscillator (MILO) in an experiment using a comparison of a ridged MILO (RMILO) with a conventional MILO (CMILO). The only technical difference between the two models is the presence of ridges in the RMILO. The experimental results show that when the voltage is 486 kV and the current is 51 kA, the RMILO’s peak microwave power is approximately 2.9 GW with a pulse duration of more than 35 ns and a microwave frequency of approximately 1.48 GHz. In contrast, the CMILO has the highest power microwave with a peak power of 2.1 GW corresponding to a pulse duration of more than 40 ns and a microwave frequency of approximately 1.53 GHz. The RMILO’s power efficiency increases to 11.7%, a 25% increase compared to that of the CMILO under the same conditions. The experimental measurements exactly coincide with the simulation results. Thus, including ridged disk vanes produces a superior performance.

Mutations in kinases are abundant and critical to study signaling pathways and regulatory roles in human disease, especially in cancer. Somatic mutations in kinase genes can affect drug treatment, both sensitivity and resistance, to clinically used kinase inhibitors. Here, we present a newly constructed database, KinaseMD (kinase mutations and drug response), to structurally and functionally annotate kinase mutations. KinaseMD integrates 679 374 somatic mutations, 251 522 network-rewiring events, and 390 460 drug response records curated from various sources for 547 kinases. We uniquely annotate the mutations and kinase inhibitor response in four types of protein substructures (gatekeeper, A-loop, G-loop and αC-helix) that are linked to kinase inhibitor resistance in literature. In addition, we annotate functional mutations that may rewire kinase regulatory network and report four phosphorylation signals (gain, loss, up-regulation and down-regulation). Overall, KinaseMD provides the most updated information on mutations, unique annotations of drug response especially drug resistance and functional sites of kinases. KinaseMD is accessible at https://bioinfo.uth.edu/kmd/, having functions for searching, browsing and downloading data. To our knowledge, there has been no systematic annotation of these structural mutations linking to kinase inhibitor response. In summary, KinaseMD is a centralized database for kinase mutations and drug response.

In this study, we investigate the effect of the inclusion of ridged disk vanes on the operation of a magnetically insulated transmission line oscillator (MILO), using a combination of “cold” (without electron beam) and “hot” (with electron beam) simulations. Cold simulation shows that the inclusion of ridged-disks in a ridged MILO (RMILO) enhances its slow wave structure’s (SWS’s) coupling impedance, thus improving its power efficiency. Moreover, since the ridges’ effect on frequency is weak, the MILO’s inherent tunability is maintained. In hot simulation, the RMILO obtains a 3-dB tunable frequency range of 0.96–2.18 GHz with an applied voltage of 603 kV, in contrast to the 1.04–2.01-GHz range obtained with a conventional MILO (CMILO), owing to the former’s improved power efficiency. With this voltage, the device generates the high power microwave (HPM) with a maximum output power of 7.1 GW at a frequency of 1.40 GHz, corresponding to a power efficiency of 22.6%. The maximum power efficiency of 24.5%, corresponding to a 13.5-GW output, was obtained by increasing the applied voltage to 807 kV, an increase of 20.2% compared to the power efficiency obtained with a CMILO in the same condition.

Faced with an increasingly tight resource supply, serious environmental pollution and degrading ecosystems, human beings are eager to reduce environmental pollution and promote public health. In this context, this paper takes the ecological civilization demonstration area (ECDA) established in China as a quasi-natural experiment to test whether ecological civilization construction (ECC) is an effective solution for the reduction of environmental pollution and improvement of public health. Based on the panel data of 31 provinces in China from 2009 to 2020, the study analyzes the impact of ECC on environmental quality and public health by employing a difference-in-difference model. The results show that ECDA has restrained environmental pollution and reduced the morbidity and mortality, which indicates that ECC effectively promotes environmental quality and public health. The effect of ECC is more pronounced in economically developed regions. In addition, ECC improves environmental quality through scale effects, structural effects, technology effects, and ecological conservation effects, while the positive effects of ECC on public health are driven by scale effects and ecological conservation effects only. Therefore, policymakers should support low-carbon production, promote the upgrade of industrial structures, and encourage enterprises to develop green technologies. Ecological protection projects such as afforestation and greening are necessary. Governments should initiate ecological civilization construction in economically developed regions and then gradually promote the policies in relatively poor areas.

AimWe sought to evaluate the efficacy of acupuncture in treating the main symptoms of primary Sjögren’s syndrome, specifically dryness, pain, and fatigue.MethodsA total of 120 patients with primary Sjögren’s syndrome were randomized in a parallel-group, controlled trial. Participants received acupuncture or sham acupuncture for the first 8 weeks, then were followed for 16 weeks thereafter. The primary outcome was the proportion of participants with a ≥ 30% reduction in ≥ 2 of 3 numeric analog scale scores for dryness, pain, and fatigue. The secondary outcomes included the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Patient-reported Index (ESSPRI); the EULAR Sjögren’s Syndrome Disease Activity Index; the Schirmer test score; unstimulated saliva flow; serum immunoglobulin G, A, and M concentrations; the Medical Outcome Study Short Form 36 score; salivary gland ultrasound imaging; and the Hospital Anxiety and Depression Scale score.ResultsThe proportions of patients meeting the primary endpoint were 28.33% (17/60) in the acupuncture group and 31.66% (19/60) in the sham group, without a statistically significant difference (P = 0.705). The IgG concentration at week 16 and the homogeneity in ultrasonography of the salivary glands at week 8 showed significant differences between the 2 groups (P = 0.0490 and P = 0.0334, respectively). No other differences were observed between the 2 groups. ESSPRI and unstimulated saliva flow were improved in both groups compared to baseline, albeit with a significant difference between them.ConclusionIn patients with primary Sjögren’s syndrome, acupuncture did not satisfactorily improve symptoms compared to placebo. However, interesting discoveries and possible underlying reasons were demonstrated and discussed, which may be useful to studies in the future.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT02691377].

Flame retardant modification of leaf fibers was carried out to solve the technical problem of poor fire resistance of plant fibers and improve the utilization rate of urban fallen leaves in building materials. The modification scheme adopts three flame retardants, i.e., ammonium polyphosphate (APP), magnesium hydroxide (MH), and aluminum hydroxide (ATH), and two covering layers, i.e., pure acrylic polymer lotion and water glass (Na

The identification of pedestrians using radar micro-Doppler signatures has become a hot topic in recent years. In this paper, we propose a multi-characteristic learning (MCL) model with clusters to jointly learn discrepant pedestrian micro-Doppler signatures and fuse the knowledge learned from each cluster into final decisions. Time-Doppler spectrogram (TDS) and signal statistical features extracted from FMCW radar, as two categories of micro-Doppler signatures, are used in MCL to learn the micro-motion information inside pedestrians' free walking patterns. The experimental results show that our model achieves a higher accuracy rate and is more stable for pedestrian identification than other studies, which make our model more practical.

Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism. Methods In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR. Findings The median age of our cohort was 73·5 years (range 42–84; IQR 67·5–77·25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue. Interpretation The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination. Funding None.

Sand control measures in horizontal wells are mainly based on screens. Horizontal wells have a certain length of horizontal displacement and the kick-off section with large curvature. Therefore, it is necessary to evaluate the safety of the screen downhole run before it runs into the hole, in order to minimize the running risk. In this paper, the pipe string is divided into sections, and the equivalent force for each elementary section is analyzed. Then, the axial force and friction resistance of the pipe string are calculated. According to the buckling criterion of the string and the mechanical strength theory, this paper evaluates whether the screen can safely and smoothly run down to the bottom of the well. This analytical method of solving the physical model is feasible and easy to understand and can be implemented using computer programming applications.

Sarcomas infrequently arise in the larynx where the vast majority of tumors are of epithelial origin. Given their rarity, studies of these lesions are limited in number. In this series, we describe our institutional experience with ten primary sarcomas of the larynx encountered over an 18 year period, comprising 1.9% of all laryngeal malignancies observed in this timeframe. The cases include four chondrosarcomas and one example each of osteosarcoma, embryonal rhabdomyosarcoma, undifferentiated spindle cell sarcoma, well-differentiated liposarcoma, Kaposi sarcoma, and synovial sarcoma. Patients included nine males and one female, with a mean age of 59 years (range 34–75). The mean clinical follow-up time was 3.4 years (range 0–12 years). Clinically, all patients presented with vocal and/or respiratory symptoms, and all received surgical treatment with the exception of the case of Kaposi sarcoma. Of the nine patients who underwent surgical excision, two, both chondrosarcomas, experienced local recurrence. No instances of distant metastasis or death of disease had occurred at the time of preparation of this manuscript. In conclusion, primary sarcomas of the larynx are rare but tend to present with early symptoms. This likely allows for earlier detection and intervention as compared to their counterparts in other deep soft tissue locations. Pathologically, it is important, although difficult in some cases, to distinguish these neoplasms from sarcomatoid carcinoma and reactive processes. Careful morphologic and immunohistochemical evaluation, as well as correlation with the clinical and radiologic findings, is important for accurate tumor classification.

Background β-Catenin/T-cell factor 4 (TCF4) signaling is enhanced in ischemic heart disease in which ventricular tachycardia (VT)/ventricular fibrillation occurs frequently. How this signaling links to arrhythmogenesis remains unclear. Objective The purpose of this study was to investigate the role of β-catenin gain of function in the development of arrhythmia. Methods A mouse model with a conditional deletion of CTNNB1 exon 3 resulting in cardiac exon 3–deleted and stabilized β-catenin (β-catΔE3) was used to determine the role of β-catenin gain of function in the regulation of cardiac rhythm. Results Western blotting showed β-catΔE3 expression and significantly decreased NaV1.5 protein in CTNNB1 E3−/− and CTNNB1 E3+/− mouse hearts. Real-time qRT-PCR revealed significantly decreased NaV1.5 messenger RNA with no changes in Na+ channel β1 to β4 expression in these hearts. Immunofluorescence revealed accumulation of β-catΔE3 in the nuclei of CTNNB1 E3−/− cardiomyocytes. Immunohistochemistry demonstrated nuclear localization of β-catenin in cardiomyocytes, which was associated with significantly decreased NaV1.5 messenger RNA in human ischemic hearts. Immunoprecipitation revealed that β-catΔE3 interacted with TCF4 in CTNNB1 E3−/− cardiomyocytes. Whole-cell recordings showed that Na+ currents and depolarization and amplitude of action potentials were significantly decreased in CTNNB1 E3−/− ventricular myocytes. Electrocardiographic recordings demonstrated that in mice with cardiac CTNNB1 E3−/−, the QRS complex was prolonged and VT was induced by the Na+ channel blocker flecainide. However, cardiac function, as determined by echocardiography and heart/body weight ratios, remained unchanged. Conclusion Enhancement of β-catenin/TCF4 signaling led to the prolongation of the QRS complex and increase in susceptibility to VT by suppression of NaV1.5 expression and Na+ channel activity in mice.

Increased nuclear β-catenin interacting with T-cell factor 4 (TCF4) affects the expression of target genes including SCN5A in ischemic heart disease, which is characterized by frequent ventricular tachycardia/fibrillation. A complex of β-catenin and TCF4 inhibits cardiac Na+ channel activity by reducing NaV1.5 expression through suppressing SCN5A promoter activity in HL-1 cardiomyocytes. LF3, a 4-thioureido-benzenesulfonamide derivative and an inhibitor of β-catenin/TCF4 interaction, has been shown to block the self-renewal capacity of cancer stem cells. We performed studies to determine if LF3 can reverse suppressive effects of β-catenin/TCF4 signaling on the expression of NaV1.5 in HL-1 cardiomyocytes. Western blotting and real-time qRT-PCR analyses showed that 10 μM LF3 significantly increased the expression of NaV1.5 but it did not alter β-catenin and TCF4 expression. Subcellular fractionation analysis demonstrated that LF3 significantly increased the levels of NaV1.5 in both membrane and cytoplasm. Whole-cell patch-clamp recordings revealed that Na+ currents were significantly increased with no changes in the steady-state parameters, activation and inactivation time constants and recovery from inactivation of Na+ channel in HL-1 cells treated with LF3. Immunoprecipitation exhibited that LF3 blocked the interaction of β-catenin and TCF4. Luciferase reporter assays performed in HEK 293 cells and HL-1 revealed that LF3 increased the SCN5A promoter activity in HL-1 cells and prevented β-catenin suppressive effect on SCN5A promoter activity in HEK 293 cells. Taken together, we conclude that LF3, an inhibitor of β-catenin/TCF4 interaction, elevates NaV1.5 expression, leading to increase Na+ channel activity in HL-1 cardiomyocytes.

With the rise and popularization of the concept of green sustainable development, green income growth of agricultural insurance policies has attracted wide attention. Whether green income growth can be achieved has become an important criterion for measuring an agricultural insurance policy. In this context, this paper attempts to test whether the agricultural insurance policy achieves green income growth. Based on the panel data of 31 provinces (the research sample of this paper selects 31 provincial-level units (province for short) in China, including 22 provinces, 5 autonomous regions and 4 municipalities directly under the central government. Hong Kong Special Administrative Region, Macau Special Administrative Region and Taiwan Province are not included in the research sample) from 2009 to 2020 in China, this paper empirically evaluates the triple-effect of total cost insurance pilot program (TCI) on farmers’ income, environment and public health by employing a difference-in-difference model (DID). The results show that TCI increases farmers’ income, but deteriorates the environment and residents’ health without achieving green income growth. In the analysis of heterogeneity, compared with central and western regions, farmers’ income is more likely to increase in the eastern regions. However, environmental pollution is more severe, and residents’ health deteriorates more, in eastern regions. In addition, the positive effect of TCI on farmers’ income and the deterioration of residents’ health is more obvious in areas with a higher degree of damage, while the negative effect of TCI on the environment is more obvious in areas with a lower degree of damage. Furthermore, the mechanism analysis shows that TCI not only promotes the increase in farmers’ income through insurance density, but also affects the environment and residents’ health through straw burning. Therefore, the government should raise the subsidy standard for farmers to use straw-processing equipment and also to implement differentiated subsidies in regions with different levels of economic development and areas with different degrees of damage.

Background: Idiopathic Hypereosinophilic Syndrome (iHES) is a rare disease with varied clinical presentations including acute heart failure. Case: A 44-year-old man who had been treated for asthma 9 months ago was admitted with worsening exertional dyspnea. EKG demonstrated sinus tachycardia with anterolateral ST depressions. Labs revealed troponin-I 44.95 ng/ml, BNP 405 pg/mL, and white blood cell count 21.2k with 50% eosinophils. Transthoracic echocardiogram showed normal left ventricular size with globally reduced ejection fraction (30-35%). Coronary angiography found normal coronary arteries. An extensive infectious and auto-immune workup was unrevealing, and bone marrow biopsy was negative for monoclonal proliferation (Fig 1A). He received 1 gram of IV methylprednisolone for 2 days lowering eosinophil count to zero and was discharged on heart failure GDMT. Two weeks later, he was readmitted from clinic for ventricular tachycardia (VT) near 120bpm (Fig 1B). Cardiac MRI and endomyocardial biopsy confirmed active eosinophilic myocarditis (Fig 1C/D). Patient was diagnosed with iHES and treated with IV methylprednisolone (500mg BID x 3 days) with an oral prednisone taper. Amiodarone and lidocaine infusions were temporarily needed to suppress his VT and an ICD was placed. After clinical stabilization and immunology consultation, an interleukin-5 inhibitor was used for further treatment of iHES. Discussion: Only 6% of patients with iHES present with cardiac symptoms, however one in five eventually develop cardiac manifestations that are often rapidly progressive. Prompt treatment with glucocorticoids is indicated for severe presentations, and subsequent use of targeted therapies can dramatically reduce morbidity and mortality. Recognition of severe peripheral eosinophilia should prompt a broad hematologic, infectious, and auto-immune workup to guide treatment and prevent end-organ damage.

The concentrations of small microplastics (diameter < 350 µm) on filters are usually determined by microscopy or micro Fourier-transform infrared spectroscopy.The presence of too many particles on a filter will cause the measured number of particles and particle sizes to be incorrect because of overlapping particles. In this study, the appropriate quantity of particles on a filter to allow effective particle analysis to be performed was determined by performing numerical experiments.The larger the number of particles and the larger the particles, the smaller the proportion of isolated particles. An isolation ratio of 99% requires a particle density on the filter of 1.28 particles mm−2 if the particle size is 50 µm or of 0.351 particles mm−2 if the particle size is 100 µm.•Appropriate number of particles for small plastic particle analysis was determined.•Numerical experiments to determine particle distributions on a filter were performed.•Particle number for a 99% isolation ratio was determined.

A nested double neuston net was prepared and used to collect samples from the surface of coastal waters around Japan to obtain information about the properties of both small microplastics (SMPs;350 μm) and large microplastics (LMPs;350 μm). The SMP concentrations ranged from 1000 to 5900 pieces m

The received signal of passive radar based on mobile communication signals contains direct and multipath interference (DMI) signals from multiple co-channel base stations (CCBS). The direct signal spatial spectrum of each CCBS should be obtained first to eliminate the co-channel interference. The performance of the traditional spatial spectrum estimation algorithms based on uniform linear array (ULA) is related to the number of array elements. In the complex co-channel interference environment, the array requires an ultra-large number of array elements and the spatial spectrum estimation resolution is poor. This paper proposes a method for estimating the direct signal spatial spectrum of the CCBS by fusing coprime array and compressive sensing. Firstly, an augmented virtual array signal is constructed by using the second-order statistics of the received signals of the coprime array and then the compressive sensing algorithm is used to estimate the spatial spectrum of the direct signal of the CCBS. The proposed method can achieve higher resolution and higher-degrees-of-freedom (DOFs) performance than traditional ULA by using the same number of array elements. The effectiveness of the proposed method is verified by numerical simulation analysis and experimental data.