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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.

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

In this paper, a new type of unit dew-point evaporative cooler with fibrous membrane was designed and constructed. The effects of three air state parameters (temperature, humidity, air velocity) on the outlet air temperature, wet-bulb efficiency and dew-point efficiency were studied, as well as the regional adaptability in four typical cities in China. The porous fibrous membrane can be used to improve the moisture permeability and diffusion characteristics of the wet channel. It was found that the wicking height rate of the porous fibrous membrane was 0.203 cm/min, the diffusivity rate was 0.118 cm2/s, which was better than the performance of Kraft Paper. The usage of this novel device in Urumqi and Lanzhou, as regions with lower relative humidity, showed better regional adaptability than in Beijing and Shanghai with higher relative humidity. When the inlet air velocity was 1 m/s, the temperature decreased from 33.4 °C to 24.2 °C and 31.3 °C–24.5 °C respectively in the former area, while, decreased from 33.6 °C to 28.1 °C and 34.6 °C–29.5 °C respectively in the latter area. With the inlet air velocity increasing from 1 m/s to 3 m/s, the outlet air temperature would rise, and the wet-bulb efficiency and dew-point efficiency would decrease, but the cooling capacity would increase.

Bone morphogenetic protein (Bmp) and Wnt pathways regulate cell proliferation and differentiation, but how these two pathways interact and mediate their nuclear actions in the heart, especially during late cardiac development, remains poorly defined. T-cell factor (TCF) and lymphoid enhancer factor (LEF) family transcriptional factors, including Lef1, Tcf7, Tcf7l1, and Tcf7l2, are important nuclear mediators of canonical Wnt/β-catenin signaling throughout cardiac development. We reveal that these TCF/LEF family members direct heart maturation through distinct temporal and spatial control. Tcf7 and Lef1 decreases while Tcf7l1 and Tcf7l2 remain relatively stable during heart development. Lef1 is mainly expressed in mesenchymal cells in valvular regions. Tcf7 and Tcf7l1 are detected in the nucleus of mesothelial and endothelial cells, but not in cardiomyocytes or mesenchymal cells. Tcf7l2 is the primary TCF/LEF family member in cardiomyocytes and undergoes alternative splicing during heart development. A Tcf7l2 intensity gradient opposite to that of β-catenin and cardiomyocyte proliferative activity is present in fetal hearts. Wnt activation by cardiac deletion of adenomatosis polyposis coli, a negative Wnt regulator, dramatically increases Cyclin D2 and Bmp4 expression. Bmp signal transducing transcription factors, the mothers against decapentaplegic homologs (Smads) are increasingly phosphorylated upon Wnt activation. Lef1/Tcf7 displaces Tcf7l2 and cooperates with pSmad1/5/8 in the regulatory elements of Cyclin D2 and Bmp4 promoters to promote β-catenin recruitment and transcriptional activation. Finally, we demonstrate that Tcf7l2 is a transcriptional suppressor of Cyclin D2 and Bmp 4 in a cardiac cell line by overexpression and knockdown experiments.

In this work, a novel anti-flame poly(ethylene terephthalate) (PET) fabric was successfully fabricated by plasma-based technology combined with pad-dry-cure treatment finishing. Low-temperature plasma can graft maleic acid (MA) onto a PET polymer backbone, which can activate the PET fiber and provide the opportunity of reaction with pentaerythritol phosphate urea salt (PEPAS) to achieve an excellent and durable anti-flame ability. Furthermore, the chemical reaction between PET-MA and PEPAS can form a complex and compact net structure that can effectively improve the anti-dripping property of PET. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and scanning electron microscopy analysis showed that MA and PEPAS were successfully introduced onto the surface of the PET fabric, and a compact protective carbon layer was formed during the combustion process due to the synergistic effect of phosphorus and nitrogen. The flame-retardant and anti-dripping properties were evaluated by thermogravimetric analysis, the limiting oxygen index (LOI) and a vertical burning test. The treated samples showed the maximum LOI value of 29.3, possessing excellent thermal stability and self-extinguishing ability and inhibiting melt-dripping ability. Moreover, tensile strength at break of the treated PET fabric was slightly greater than that of the original PET fabric, indicating that this type of treatment had little negative impact on the bulk of the PET fabric. After 20 laundering cycles, the LOI value of the treated sample still remained at 26.8, which indicated durability in the flame-retarding effect.

High levels of glutamate dehydrogenase (GDH) activity are associated with hypoglycemia, cancer, and Parkinson's disease. Propylselen was synthesized to investigate its mechanism of GDH inhibition in comparison with Ebselen and Epigallocatechin gallate (EGCG). Because Ebselen was found to crosslink with the peptide (AA299-341) at the active site of E.coli GDH, the Cys, Pro, and Lys residues of the corresponding peptide were mutagenized to Ala residues. Using enzyme kinetics and biomolecular interaction assays, we found that the conserved GDH P320 residue is important for propylselen binding, C321 for Ebselen binding, and K341 for EGCG binding. In addition, these 3 mutations abolished NADP+ binding to E. coli GDH in the absence of glutamate substrate, but in the presence of glutamate, the catalytic activity of the mutants was reduced only by 2–4 fold, indicating that a substrate-induced fit mechanism exists in E. coli GDH. Furthermore, biochemical analysis showed that NADP+ had high affinity (Kd of 77 nM) for GDH; by targeting the NADP binding site, propylselen effectively inhibited both E. coli and human GDH activity and improved anticancer activity.

Purpose/Objectives: The human tumor microenvironment (TME) has a dramatic impact on cancer prognosis and therapeutic response, but accurate models of the native TME do not exist. The Comparative In Vivo Oncology (CIVO) platform was developed as a means to assess the effect of investigational agents on the native TME in a Phase 0 microdosing study. CIVO was clinically validated using approved agents and is used for the first time here to assess the impact of an investigational agent - the SUMOylation inhibitor TAK-981 - on the native human TME in HNSCC. Materials/Methods: Eligible subjects have a confirmed HNSCC diagnosis, ECOG 0-2, and planned surgical resection. Injectable tumors were at the primary site or within cervical lymph nodes but had to be surface-accessible and ≥ 2cm. TAK-981 or control microdoses were simultaneously administered via a CIVO device and co-injected with a fluorescent tracking marker for injection site identification and visualization. Tumors were resected 24 or 72 hours after injection, processed, and then analyzed at a central site. Multiplexed biomarker staining and molecular profiling via GeoMx Digital Spatial Profiling were performed to capture pharmacodynamic responses in the native TME. Results: As of January 2022, 8 subjects provided informed consent and were enrolled, and no adverse events associated with the injection procedure or microdoses have been reported. Biomarker analysis demonstrated TAK-981 distribution around the injection site accompanied by reduction of SUMOylation. Dose-dependent elevation of IFN1 signaling was also observed in TAK-981-exposed areas within the TME. Elevated IFN1 signaling was accompanied by TME reconfiguration, with increased macrophage M1 polarization and activation of dendritic cells, NK cells, and CD8+ T cells. TAK-981 exposure was also associated with upregulation of CXCL10, PD-L1, and an IFNγ gene expression signature predictive of response to immune checkpoint blockade. Conclusion: IT microdosing with CIVO provided early insights into complex functional responses induced by the investigational agent TAK-981 that can only be accurately evaluated in the intact, native TME of a patient’s tumor. SUMO pathway inhibition in HNSCC tumors following TAK-981 exposure led to functional activation of multiple immune cell types, effectively shifting the local TME toward an inflamed “hot” state, highlighting TAK-981’s potential as an immune stimulating agent for treating patients with solid tumors. These data were generated while TAK-981 was still in Phase I dose escalation trials (via IV administration), highlighting CIVO’s ability to safely study investigational agents. Further evaluation of TAK-981 alone and in combination with other agents is ongoing in this Phase 0 CIVO microdosing trial. Citation Format: Jeffrey Houlton, Harrison Cash, Haodong Xu, Paul L. Swiecicki, Keith Casper, Steven B. Chinn, Daniel R. Clayburgh, Ryan J. Li, Robert J. Christian, Aaron Halfpenny, Annemieke van Zante, Beryl A. Hatton, Kimberly Sottero, Marc O. Grenley, Connor Burns, Jason Frazier, Jonathan Derry, Gloria Kung, Emily Beirne, Nathan J. Schauer, Atticus Turner, Wendy Jenkins, Kirsten Anderson, Richard A. Klinghoffer, Dennis Huszar, Allison Berger, Karuppiah Kannan. Intratumoral (IT) microdosing of the investigational SUMOylation Inhibitor TAK-981 in a phase 0 CIVO trial demonstrates the reactivation of type I Interferon (IFN1) signaling in head and neck squamous cell carcinoma (HNSCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT139.

In this paper, we present the design, fabrication, and test of a micro-opto-electro-mechanical systems (MOEMS) accelerometer based on the Talbot effect of double-layer diffraction gratings. The detection of acceleration is realized by using the highly sensitive displacement characteristic of Talbot imaging of near-field diffraction with double-layer gratings. For the purpose of obtaining optimal contrast of the optical interferometric detection, the parameters of the gratings are optimized by the finite-difference time-domain (FDTD) simulation. The experimental results indicate that this MOEMS accelerometer with the proposed design can achieve a resolution of 246 µg, sensitivity of 6.1 V/g, and bias stability of 0.02 mg. The proposed accelerometer can be operated at higher accelerations ( ∼ 80 g ), which shows significant potential for being used in applications that require detection of strong and fast vibrations, especially in vibration sensing of vehicles and geophysical seismic sensing in real time.

The sensitive detection of sound waves is essential for a variety of applications. In this work, we propose a miniature diaphragm-free fiber-optic microphone based on a plano-concave optical micro-interferometer. A solid plano-concave micro-interferometer is formed at the end of a cleaved fiber by depositing a tiny volume of liquefied glass. Sound wave induced periodic variation of pressure can significantly modify the refractive index of the plano-concave glass due to the elasto-optic effect, and then, the phase difference between two interferometric beams will be remarkably changed accordingly. The interferometer finally converts the fluctuation of the phase difference into the change in the output optical power. Consequently, the sound wave can be demodulated by detecting the output power of the microphone. The experimental results show that the proposed microphone has the ability to detect sound waves in the whole audible range and almost omnidirectional. The noise-limited minimum detectable sound pressure is around 12 µPa[Formula: see text]. In addition, the human voice detection test shows that the performance of our microphone is competitive with the most advanced commercial device. The structure is stable without any movable mechanical parts, and the size is as small as 0.25 mm, which makes the proposed microphone an attractive alternative to the conventional one for sound wave detection.

The BIG Data Center at Beijing Institute of Genomics (BIG) of the Chinese Academy of Sciences provides a suite of database resources in support of worldwide research activities in both academia and industry. With the vast amounts of multi-omics data generated at unprecedented scales and rates, the BIG Data Center is continually expanding, updating and enriching its core database resources through big data integration and value-added curation. Resources with significant updates in the past year include BioProject (a biological project library), BioSample (a biological sample library), Genome Sequence Archive (GSA, a data repository for archiving raw sequence reads), Genome Warehouse (GWH, a centralized resource housing genome-scale data), Genome Variation Map (GVM, a public repository of genome variations), Science Wikis (a catalog of biological knowledge wikis for community annotations) and IC4R (Information Commons for Rice). Newly released resources include EWAS Atlas (a knowledgebase of epigenome-wide association studies), iDog (an integrated omics data resource for dog) and RNA editing resources (for editome-disease associations and plant RNA editosome, respectively). To promote biodiversity and health big data sharing around the world, the Open Biodiversity and Health Big Data (BHBD) initiative is introduced. All of these resources are publicly accessible at http://bigd.big.ac.cn.

BackgroundSARS-CoV-2 is the cause of an ongoing pandemic with a projected 100,000 to 240,000 U.S. deaths. To date, documentation of histopathologic features in fatal cases of COVID-19 has been limited due to small sample size and incomplete organ sampling.MethodsPost-mortem examinations were performed on 12 fatal COVID-19 cases in Washington State during February-March 2020. Clinical and laboratory data were reviewed. Tissue examination of all major organs was performed by light microscopy and electron microscopy. The presence of viral RNA in sampled tissues was tested by RT-PCR.ResultsAll 12 patients were older with significant preexisting comorbidities. The major pulmonary finding was diffuse alveolar damage in the acute and/or organizing phases with virus identified in type I and II pneumocytes by electron microscopy. The kidney demonstrated viral particles in the tubular epithelium, endothelium, and podocytes without significant inflammation. Viral particles were also observed in the trachea and large intestines. SARS-CoV-2 RNA was detected in the cardiac tissue of a patient with lymphocytic myocarditis. RT-PCR also detected viral RNA in the subcarinal lymph nodes, liver, spleen, and large intestines.ConclusionSARS-CoV-2 represents the third novel coronavirus to cause widespread human disease since 2002. Similar to SARS and MERS, the primary pathology was diffuse alveolar damage with virus located in the pneumocytes. However, other major organs including the heart and kidneys may be susceptible to viral replication and damage leading to increased mortality in those with disseminated disease. Understanding the pathology of SARS-CoV-2 will be essential to design effective therapies.

The bone morphogenetic protein (BMP) signaling pathway is highly conserved across many species, and its importance for the patterning of the skeletal system has been demonstrated. A disrupted BMP signaling pathway results in severe skeletal defects. Murine calvaria has been identified to have dual-tissue lineages, namely, the cranial neural-crest cells and the paraxial mesoderm. Modulations of the BMP signaling pathway have been demonstrated to be significant in determining calvarial osteogenic potentials and ossification in vitro and in vivo. More importantly, the BMP signaling pathway plays a role in the maintenance of the homeostasis of the calvarial stem cells, indicating a potential clinic significance in calvarial bone and in expediting regeneration. Following the inherent evidence of BMP signaling in craniofacial biology, we summarize recent discoveries relating to BMP signaling in the development of calvarial structures, functions of the suture stem cells and their niche and regeneration. This review will not only provide a better understanding of BMP signaling in cranial biology, but also exhibit the molecular targets of BMP signaling that possess clinical potential for tissue regeneration.

Histopathologic diagnosis of antibody-mediated rejection in posttransplant liver biopsies is challenging. The recently proposed diagnostic criteria by the Banff Working Group on Liver Allograft Pathology require positive C4d immunohistochemical staining to establish the diagnosis. However, the reported C4d staining patterns vary widely in different studies. One potential explanation may be due to different antibody preparations used by different investigators. In this study, posttransplant liver biopsies from 69 patients histopathologically diagnosed with acute cellular rejection, chronic rejection, or recurrent hepatitis C were immunohistochemically stained using 2 polyclonal anti-C4d antibodies. On the basis of the distribution of C4d immunoreactivity, 5 different staining patterns were observed: portal vein and capillary, hepatic artery, portal stroma, central vein, and sinusoids. The frequency, extent, and intensity of positive C4d staining with the 2 antibody preparations differed significantly for portal veins/capillaries and central veins, but not for hepatic arteries and portal stroma. Positive sinusoidal staining was seen in only 1 case. There were no significant differences in the frequency, extent, and intensity of positive C4d staining among the acute cellular rejection, chronic rejection, and recurrent hepatitis C groups with the 2 anti-C4d antibodies. These data show that different anti-C4d antibodies can show different staining patterns, which may lead to different interpretation. Caution is thus needed when selecting C4d antibodies for clinical use to aid in the diagnosis of antibody-mediated rejection.

A method to calculate entransy change (ΔE) and thermal resistance (R) was proposed firstly in this paper. The experimental results showed that in the wet channel the R was decreased and the total heat exchange capacity (Q t ) was increased gradually along the air flow at the condition of Turpan and Shanghai, but showed a different trend in Lanzhou. Meanwhile, in the dry channel the cooling capacity (Q) and temperature drop (ΔT) were decreased along the air flow in all three regions. As inlet temperature increased, the R was decreased and Q t was increased in wet channel, thus the Q and the cooling rate in dry channel were increased. With inlet humidity ratio and air velocity decreased in dry channel, the R in wet channel was increased firstly and then decreased. The lowest inlet humidity ratio was, the smallest R in wet channel was, the highest Q and temperature drop rate in dry channel were. At the velocity 1.8 m/s, the R dropped to the lowest point, after that, Q was increased slowly and the temperature drop rate was reduced in the dry channel, therefore, high air velocity would only make Q increased but attribute to poor cooling effect. Then, some improved methods of the experimental device were proposed by the theory and experiment. Finally, some comparisons were made between conventional evaluation indicators and the new one proposed in this paper, it can be concluded that each indicator has its own strength and shortages, in the practical application, the proper indicator should be selected according to the demand.

Molecular dynamics (MD) simulations are employed to probe the crystallization and precipitation behaviors in FeCu alloys. The alloys will undergo liquid phase separation at high temperature, after which α-Fe nucleates preferentially, then metastable Cu solid solutions in BCC lattice (e` phase) nucleate and transform into FCC structure (e-Cu) via martensite phase transformation immediately. Reversible order-disorder transformation behavior is observed during time-consuming crystallization process of e-Cu. Interestingly, the e`-Cu with only approximately three atomic layers in thickness exists stably near BCC/FCC α/e interface at room temperature, following the Kurdjumov–Sachs (K–S) orientation relationship. The lower nucleation energy and interface energy are the reasons for the existence of abnormal e`-Cu at the interface. It is also found that the composition and cooling rate play key roles on the final phase structure. The alloys can be fully crystallized upon cooling down at a rate of 0.1 K/ps.

This study investigated small microplastic particle (SMP, < 350 μm) contamination in the surface seabed sediment of the inner part of Tokyo Bay. The SMP concentration during the rainy season (May) was 100.3 ± 45.8 pieces g−1 dry weight and higher in the inner side of the bay, whereas that of the dry season (January) was 147.6 ± 19.5 pieces g−1 dry weight.There was no seasonal difference. The main plastic types found in the rainy season were polypropylene (PP), polyethylene (PE), and polyamide (PA). In the dry season (January), the concentration of PP decreased while that of PA increased.The mean SMP diameter did not change by site or season. Our results indicate that the seabed sediments in the inner part of Tokyo Bay are contaminated with relatively high concentrations of SMPs.Furthermore, the deposition rate of SMPs in the inner part of the bay was 12.4 mg cm−2 y−1., 公開日: 2023-09-01

Genetic manipulation of key components of the evolutionally conserved Hippo pathway has shown that the precise control of these signaling molecules is critical to cardiac development and response to stresses. However, how this pathway is involved in the progression of cardiac dysfunction in different heart diseases remains unclear. We investigated the expressional levels and subcellular localization of Yap1, Taz, and Tead1 and determined Hippo target gene expression in failing human hearts with ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (IDC) and mouse desmin-related cardiomyopathy (DES). Our results demonstrated that Yap1, Taz, and Tead1 were significantly increased in failing human and DES hearts compared with the non-failing controls (NFH) or wild type (WT) mouse hearts at both mRNA and protein levels. Interestingly, adult human and mouse hearts had more Taz than Yap1 by mRNA and protein expression and their increases in diseased hearts were proportional and did not change Yap1/Taz ratio. Yap1, Taz, and Tead1 were accumulated in the nuclear fraction and cardiomyocyte nuclei of diseased hearts. The ratio of Yap1 phosphorylated at serine 127 (human) or serine 112 (mouse) to the total Yap1 (pYap1/Yap1) was significantly lower in the nuclear fraction of diseased hearts than that in normal controls. More importantly, Hippo downstream targets Ankrd1, Ctgf, and Cyr61 were transcriptionally elevated in the diseased hearts. These results suggest that Yap1/Taz signaling is activated in human and mouse dysfunctional hearts. Further investigation with relevant animal models will determine whether this pathway is a potential target for preventing and reversing abnormal remodeling during the progression of different cardiac disorders.