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Vitamin B12 is an essential nutrient acquired via dietary intake. Receptor-mediated endocytosis is a key mechanism in vitamin B12 absorption, cellular uptake, and reabsorption. CD320 is a type I transmembrane protein responsible for cellular uptake of vitamin B12 in peripheral tissues. In this study, we examined segmental distribution and cellular expression of CD320 in mouse kidneys and intestines. We show that CD320 is expressed on the luminal surface in the small intestine and in proximal tubules in the kidney, suggesting that, in addition to its role in vitamin B12 uptake in peripheral tissues, CD320 may participate in vitamin B12 absorption in the small intestine and reabsorption in the kidney. Moreover, we show that an amino acid motif, DSSDE, in the second low-density lipoprotein receptor class A domain of CD320 is a key apical membrane targeting signal in both renal and intestinal epithelial cells. Mutations or deletion of this motif abolish the specific apical membrane expression of CD320 in polarized Madin-Darby canine kidney cells and human colon cancer-derived Caco-2 cells. In short-hairpin RNA-based gene knockdown experiments, we show that the apical membrane targeting of CD320 is mediated by a Rab11a-dependent mechanism. These results extend our knowledge regarding the cell biology of CD320 and its role in vitamin B12 metabolism.

The biological and clinical significance of the p.E88del variant in the transcobalamin receptor, CD320, is unknown. This allele is annotated in ClinVar as likely benign, pathogenic, and of uncertain significance. To determine functional consequence and clinical relevance of this allele, we employed cell culture and genetic association studies. Fibroblasts from sixteen CD320 p.E88del homozygotes exhibited reduced binding and uptake of cobalamin. Complete ascertainment of newborns with transiently elevated C3 (propionylcarnitine) in New York State demonstrated that homozygosity for CD320 p.E88del was over-represented (7/348, p

Introduction: Identifying differences in outcome of basilar artery occlusion (BAO) between males and females may be useful in aiding clinical management. Recent studies have demonstrated widespread underrepresentation of women in acute stroke clinical trials. This international multicentre study aimed to determine sex differences in outcome after mechanical thrombectomy (MT) for patients with acute BAO. Methods: We performed a retrospective analysis of consecutive patients with BAO who had undergone MT in seven stroke centres across five countries (Singapore, Taiwan, United Kingdom, Sweden, and Germany), between 2015 and 2020. Primary outcome was a favourable functional outcome measured by a modified Ranking Scale (mRS) of 0–3 at 90 days. Secondary outcomes were mRS 0–3 upon discharge, mortality, symptomatic intracranial haemorrhage (sICH) and subarachnoid haemorrhage (SAH). Results: Among the 322 patients who underwent MT, 206 (64.0%) patients were male and 116 (36.0%) were female. Females were older than males (mean ± SD 70.9 ± 14.3 years vs. 65.6 ± 133.6 years; p = 0.001) and had higher rates of atrial fibrillation (38.9% vs. 24.2%; p = 0.012). Time from groin puncture to reperfusion was shorter in females than males (mean ± SD 57.2 ± 37.2 min vs. 71.1 ± 50.9 min; p = 0.021). Despite these differences, primary and secondary outcome measures were similar in females and males, with comparable rates of favourable 90-day mRS scores (mean ± SD 46 ± 39.7 vs. 71 ± 34.5; OR = 1.20; 95% confidence interval [CI] = 0.59–2.43; p = 0.611), favourable discharge mRS scores (mean ± SD 39 ± 31.6 vs. 43 ± 25.9; OR = 1.38; 95% CI = 0.69–2.78; p = 0.368) and in-hospital mortality (mean ± SD 30 ± 25.9 vs. 47 ± 22.8; OR = 1.15; 95% CI = 0.55–2.43; p = 0.710. Rates of complications such as sICH (mean ± SD 5 ± 4.3 vs. 9 ± 4.4; OR = 0.46; 95% CI = 0.08–2.66; p = 0.385) and SAH (mean ± SD 4 ± 3.4 vs. 5 ± 2.4; OR = 0.29; 95% CI = 0.03–3.09; p = 0.303) comparably low in both groups. Conclusion: Females achieved comparable functional outcomes compared with males after undergoing MT for BAO acute ischemic stroke.

To date, only a handful of studies have described application of organic materials as carriers (nuclei) in the aerobic granular sludge (AGS) system, compared to inorganic materials.

SUMMARYCarotenoids perform a broad range of important functions in humans; therefore, carotenoid biofortification of maize (Zea maysL.), one of the most highly produced cereal crops worldwide, would have a global impact on human health.PLASTID TERMINAL OXIDASE(PTOX) genes play an important role in carotenoid metabolism; however, the possible function ofPTOXin carotenoid biosynthesis in maize has not yet been explored. In this study, we identified the maizePTOXgeneZmPTOX1by forward genetic screening.While most higher plant species possess a single copy of thePTOXgene, maize carries two tandemly duplicated copies ofZmPTOX. Characterization ofZmptox1mutants revealed that disrupting one copy ofZmPTOX1was enough to impair carotenoid biosynthesis, indicating thatZmPTOX1is essential for carotenoid biosynthesis in maize kernels. Remarkably, overexpression ofZmPTOX1significantly improved the content of carotenoids, especially β-carotene (provitamin A), which was increased by ~3-fold, in maize kernels.Overall, our study shows thatZmPTOX1plays a crucial role in carotenoid biosynthesis in maize kernels and suggests that fine-tuning the expression of this gene could improve the nutritional value of cereal grains.

Severe asthma is heterogeneous, with childhood-onset asthma believed more likely to be allergic, whereas adult-onset asthma is considered typically non-allergic. However, the allergic diagnosis is typically by exclusion: if patients do not react to an allergen panel, which is not standardized and often limited to few allergens, they are considered non-allergic. The overall aim of the ATLAS study was to characterize the sensitization to allergens in severe asthma (independent of phenotype). Single-visit, cross-sectional, non-interventional study in adults with severe asthma. Analyses were conducted for total and specific immunoglobulin E against 53 allergens, overall and in subgroups, including age at asthma onset (40 years of age). Among 1010 recruited patients, 28.4% reported childhood-onset asthma and 33.6% onset >40 years of age. After excluding patients receiving omalizumab/anti-IL5 therapy, 27.6% were not sensitized to any tested allergens, whereas 19.1% were sensitized to >10 allergens. All allergens triggered sensitization in some patients. Baseline characteristics in the two onset subgroups were similar; 23.2% with childhood-onset asthma were not sensitized to any allergen, compared to 32.0% with onset >40 years of age. When a broad panel of allergens is used for sensitization testing, as many as three quarters of patients with severe asthma display sensitivity to at least one allergen, with substantial overlaps in all characteristics between the two age-at-onset subgroups. All of the tested allergens triggered a response in at least some patients, emphasizing the importance of including a broad range of allergens in any testing panel.

Altered cell-derived microparticles (MPs) have been reported in multiple autoimmune diseases. However, the roles of megakaryocyte- and platelet-derived MPs (MKMPs and PMPs) in immune thrombocytopenia (ITP) have not been investigated. In this study, we examined plasma MKMP and PMP levels in patients with ITP and evaluated their potential diagnostic values. Plasma MKMP and PMP levels were analyzed by flow cytometry in a discovery set of ITP patients (n = 78), non-immune thrombocytopenia (TP) patients (n = 69), and age- and gender-matched healthy controls (n = 88). Samples from a therapy set of ITP patients (n = 21) were used to assess the response to thrombopoietin receptor agonist (TPO-RA) treatment. Spearman correlation analysis was performed between MP levels and disease parameters. Receiver operator characteristic (ROC) curves were generated to evaluate the diagnostic values of the MPs. We found that plasma MKMP and PMP levels were significantly lower in ITP patients than those in healthy controls (p values < 0.0001) but higher than in those in TP patients (p < 0.002 and p < 0.0002, respectively). After normalization to platelet counts, PMP/Platelet ratios in ITP patients were higher than those in TP patients and healthy controls (p values < 0.001). PMP/Platelet ratios had a diagnostic value for ITP (area under the curve = 0.808, p < 0.0001) with 73.1% sensitivity and 77.3% specificity. MKMP levels can be used to discriminate ITP from TP with a cut-off value of 112.5 MPs/μL and a sensitivity of 74.4%. Moreover, both MKMP and PMP levels were elevated in ITP patients who responded to TPO-RA treatment. Plasma PMP levels positively correlated with platelet counts in the responders (r = 0.558, p < 0.01). Our results indicate that plasma MKMP and PMP levels are decreased in ITP patients and that plasma MKMP and PMP levels may serve as biomarkers for ITP diagnosis and prediction of TPO-RA treatment response.

Sessile organisms such as plants have adopted diverse reactive oxygen species (ROS) scavenging mechanisms to mitigate damage under abiotic stress conditions. Though CGFS-type glutaredoxin (GRX) genes are important regulators of ROS homeostasis, each of their functions in crop plants have not yet been well understood. We performed a targeted mutagenesis analysis of four CGFS-type GRXs (SlGRXS14, SlGRXS15, SlGRXS16, and SlGRXS17) in tomato plants (Solanum lycopersicum) using a multiplex clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system and found that Slgrxs mutants were more sensitive to various abiotic stresses compared to the wild-type tomatoes. Slgrxs15 mutants were embryonic lethal. Single, double, and triple combinations of Slgrxs14, 16, and 17 mutants were examined under heat, chilling, drought, heavy metal toxicity, nutrient deficiency, and short photoperiod stresses. Slgrxs14 and 17 mutants showed hypersensitivity to almost all stresses while Slgrxs16 mutants were affected by chilling stress and showed milder sensitivity to other stresses. Additionally, Slgrxs14 and 17 mutants showed delayed flowering time. Our results indicate that the CGFS-type SlGRXs have specific roles against abiotic stresses, providing valuable resources to develop tomato and, possibly, other crop species that are tolerant to multiple abiotic stresses by genetic engineering. This article is protected by copyright. All rights reserved.

Proprotein convertase subtilisin/kexin 6 (PCSK6) is a secreted serine protease expressed in most major organs, where it cleaves a wide range of growth factors, signaling molecules, peptide hormones, proteolytic enzymes, and adhesion proteins. Studies in Pcsk6-deficient mice have demonstrated the importance of Pcsk6 in embryonic development, body axis specification, ovarian function, and extracellular matrix remodeling in articular cartilage. In the cardiovascular system, PCSK6 acts as a key modulator in heart formation, lipoprotein metabolism, body fluid homeostasis, cardiac repair, and vascular remodeling. To date, dysregulated PCSK6 expression or function has been implicated in major cardiovascular diseases, including atrial septal defects, hypertension, atherosclerosis, myocardial infarction, and cardiac aging. In this review, we describe biochemical characteristics and posttranslational modifications of PCSK6. Moreover, we discuss the role of PCSK6 and related molecular mechanisms in cardiovascular biology and disease.

Increasing populations and temperatures are expected to escalate food demands beyond production capacities, and the development of maize lines with better performance under heat stress is desirable. Here, we report that constitutive ectopic expression of a heterologous glutaredoxin S17 from Arabidopsis thaliana (AtGRXS17) can provide thermotolerance in maize through enhanced chaperone activity and modulation of heat stress-associated gene expression. The thermotolerant maize lines had increased protection against protein damage and yielded a sixfold increase in grain production in comparison to the non-transgenic counterparts under heat stress field conditions. The maize lines also displayed thermotolerance in the reproductive stages, resulting in improved pollen germination and the higher fidelity of fertilized ovules under heat stress conditions. Our results present a robust and simple strategy for meeting rising yield demands in maize and, possibly, other crop species in a warming global environment.

Atrial natriuretic peptide (ANP) is of major importance in the maintenance of electrolyte balance and normal blood pressure. Reduced plasma ANP levels are associated with the increased risk of cardiovascular disease. Corin is a type II transmembrane serine protease that converts the ANP precursor to mature ANP. Corin deficiency prevents ANP generation and alters electrolyte and body fluid homeostasis. Corin is synthesized as a zymogen that is proteolytically activated on the cell surface. Factors that disrupt corin folding, intracellular trafficking, cell surface expression, and zymogen activation are expected to impair corin function. To date, CORIN variants that reduce corin activity have been identified in hypertensive patients. In addition to the heart, corin expression has been detected in non-cardiac tissues, where corin and ANP participate in diverse physiological processes. In this review, we summarize the current knowledge in corin biosynthesis and post-translational modifications. We also discuss tissue-specific corin expression and function in physiology and disease.

A wide variety of drugs and substances have the potential to damage the respiratory system by different mechanisms. Clofazimine is an anti-leprosy drug that is normally only prescribed for a few years. It has a very long half-life, and crystalline deposition of the drug in various tissues has been documented. But up to now, no fatalities due to pulmonary damage have been described. We report the case of a patient who took clofazimine for almost 27 years as off-label treatment for Melkersson-Rosenthal syndrome. He suffered from progressive dyspnea, productive cough, and occasional hemoptysis. X-ray and CT of the thoracic organs revealed extensive multilocular, compact, tumor-like infiltrates with central necrosis in both lungs. Pulmonary function tests showed restrictive impairment and manifest hypoxemia. Histology of lung biopsies revealed intense interstitial accumulation of histiocytes and marked deposition of crystalline foreign material. The patient died from progressive respiratory failure. Autopsy revealed crystalline deposition and a histiocytic reaction in many other parenchymal organs. Conclusion: Pulmonary parenchymal deposition of drug crystals is a rare mechanism of drug-induced pulmonary diseases. Long-standing, off-label use of clofazimine may cause severe destruction of the lungs and can be fatal.

The vital function of mitochondrial alternative oxidase (AOX) pathway in optimizing photosynthesis during plant de-etiolation has been well recognized. However, whether and how AOX impacts the chloroplast biogenesis in algal cells remains unclear. In the present study, the role of AOX in regulating the reassembly of chloroplast in algal cells was investigated by treating Auxenochlorella protothecoides with salicylhydroxamic acid (SHAM), the specific inhibitor to AOX, in the heterotrophy to autotrophy transition process. Several lines of evidences including delayed chlorophyll accumulation, lagged reorganization of chloroplast structure, altered PSI/PSII stoichiometry, and declined photosynthetic activities in SHAM treated cells indicated that the impairment in AOX activity dramatically hindered the development of functioning chloroplast in algal cells. Besides, the cellular ROS levels and activities of antioxidant enzymes were increased by SHAM treatment, and the perturbation on the balance of NAD+/NADH and NADP+/NADPH ratios was also observed in A. protothecoides lacking AOX activity, indicating that AOX was essential in promoting ROS scavenging and keeping the redox homeostasis for algal chloroplast development during greening. Overall, our study revealed the essentiality of mitochondrial AOX pathway in sustaining algal photosynthetic performance and provided novel insights into the physiological roles of AOX on the biogenesis of photosynthetic organelle in algae.

To analyze the network alteration characteristics of brain structure network in patients with delayed encephalopathy after CO poisoning (DEACMP) based on diffusion tensor imaging (DTI), and to explore the structural correlation neuroimaging mechanism of DEACMP cognitive impairment. DTI scanning was performed in 33 patients with DEACMP and 25 healthy controls (HCs) who were matched in age and sex. The whole brain was divided into 90 regions by automated anatomical marker templates. The continuous tracing method was used to reconstruct the brain fiber bundle connection and construct the brain structure weighted network. The global and regional properties were computed by graph theoretical analysis. To compare the brain network regional properties between the DEACMP group and the HCs group, two-sample t test (false discovery rate correction, P

Plant mitochondrial phosphate transporters regulate phosphate transport and ATP synthesis. Determining whether they function in abiotic stress response process would shed light on their response to salt stress. We used the CRISPR/Cas9 gene-editing system to mutagenize two mitochondrial phosphate transporters, OsMPT3;1 and OsMPT3;2, to investigate their regulatory roles under salt stress. Two cas9 (CRISPR-associated protein 9)-free homozygous mutants, mpt33 and mpt30, were confirmed to be stable. Both OsMPT3;1 and OsMPT3;2 were markedly induced by salt stress, and their mutagenesis strongly inhibited growth and development, especially under salt stress. Mutagenesis sharply reduced the accumulation of ATP, phosphate, calcium, soluble sugar, and proline and increased osmotic potential, malondialdehyde, and Na+/K+ ratio under salt stress. Both mutants demonstrate normal growth and development in the presence of ATP, revealing high sensitivity to exogenous ATP under salt stress. The mutants showed lowered rates of Na+ efflux but also of K+ and Ca2+ influx under salt stress. Mutagenesis of OsMPT3;2 altered the enrichment profiles of differentially expressed genes involved mainly in synthesis of secondary metabolites, metabolism of glycolysis, pyruvate, tricarboxylic acid cycle, in response to salt stress. The mutant displayed significant accumulation differences in 14 metabolites involved in 17 metabolic pathways, and strongly up-regulated the accumulation of glutamine, a precursor in proline synthesis, under salt stress. These findings suggest that the OsMPT3 gene modulates phosphate transport and energy supply for ATP synthesis and triggers changes in accumulation of ions and metabolites participating in osmotic regulation in rice under salt stress, thus increasing rice salt tolerance. This study demonstrates the effective application of CRISPR/Cas9 gene-editing to the investigation of plant functional genes.

Hepsin is a transmembrane serine protease primarily expressed in the liver. To date, the physiological function of hepsin remains poorly defined. Here we report that hepsin-deficient mice have low levels of blood glucose and lipids and liver glycogen, but increased adipose tissue browning and basal metabolic rates. The phenotype is caused by reduced hepatocyte growth factor activation and impaired Met signaling, resulting in decreased liver glucose and lipid metabolism and enhanced adipocyte browning. Hepsin-deficient mice exhibit marked resistance to high-fat diet-induced obesity, hyperglycemia, and hyperlipidemia. In db/db mice, hepsin deficiency ameliorates obesity and diabetes. These data indicate that hepsin is a key regulator in liver metabolism and energy homeostasis, suggesting that hepsin could be a therapeutic target for treating obesity and diabetes.

Objective: Pediatric primary cardiac tumor is an extremely rare disease. The tumor can extend into the conduction system and cause malignant arrhythmias. We retrospectively reviewed 6 consecutive cases of children with primary cardiac tumor that manifested as rhythm disturbance. Methods: In our center, 6 children were enrolled from October 2009 to August 2016. Detailed operative data and follow-up information were comprehensively collected and statistically analyzed. Results: The patients were ages 1 to 16 years and weighed 7.9 to 44.5 kg. Preoperative ventricular tachycardia was present in 3 patients, frequent ventricular ectopic beats in 1 patient, supraventricular tachycardia in 1 patient, and atrial flutter in 1 patient. All 6 patients underwent a complete tumor resection. The tumors were localized in the left ventricular free wall (3 patients), left ventricular outflow tract (1 patient), left atrium (1 patient), and right atrium (1 patient). One patient received 2 radiofrequency ablation procedures before tumor resection. Postoperative sick sinus syndrome occurred in 1 patient because the tumor infiltrated the sinoatrial node. Tumors from 2 patients were pathologically diagnosed as fibroma and 4 as rhabdomyoma. Reoperation of mitral valve repair was performed in 1 patient 1 year after tumor resection. The mean (± SD) follow-up time was 63.7 ± 31.4 months, and all children were well, with Ross functional classification I and no signs of recurrence or metastasis. Conclusions: In conclusion, cardiac tumor is a rare but nonneglectable reason for arrhythmia, and surgical resection is the optimal procedure, with satisfactory results.

Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is a protein tyrosine phosphatase that negatively regulates T-cell signaling. However, whether it is expressed and functions in platelets remains unknown. Here we investigated the expression and role of PTPN22 in platelet function. We reported PTPN22 expression in both human and mouse platelets. Using PTPN22−/− mice, we showed that PTPN22 deficiency significantly shortened tail-bleeding time and accelerated arterial thrombus formation without affecting venous thrombosis and the coagulation factors VIII and IX. Consistently, PTPN22-deficient platelets exhibited enhanced platelet aggregation, granule secretion, calcium mobilization, lamellipodia formation, spreading, and clot retraction. Quantitative phosphoproteomic analysis revealed the significant difference of phosphodiesterase 5A (PDE5A) phosphorylation in PTPN22-deficient platelets compared with wild-type platelets after collagen-related peptide stimulation, which was confirmed by increased PDE5A phosphorylation (Ser92) in collagen-related peptide–treated PTPN22-deficient platelets, concomitant with reduced level and vasodilator-stimulated phosphoprotein phosphorylation (Ser157/239). In addition, PTPN22 interacted with phosphorylated PDE5A (Ser92) and dephosphorylated it in activated platelets. Moreover, purified PTPN22 but not the mutant form (C227S) possesses intrinsic serine phosphatase activity. Furthermore, inhibition of PTPN22 enhanced human platelet aggregation, spreading, clot retraction, and increased PDE5A phosphorylation (Ser92). In conclusion, our study shows a novel role of PTPN22 in platelet function and arterial thrombosis, identifying new potential targets for future prevention of thrombotic or cardiovascular diseases.

In this study, we aimed to assess the effects of probiotic administration on the digestibility characteristics and growth performance of finishing beef cattle fed a total mixed ration (TMR) containing different levels of corn stover. One hundred and sixty Simmental × Continental crossbred bulls were randomly allocated to two animal houses (80 bulls each) and randomly assigned four TMR differing in the level of corn stover-high (HCT) and low (LCT)-with or without probiotics in each animal house. Feeding HCT supplemented with probiotics increased (P 0.05) the apparent digestibility of crude protein (CP), ether extract (EE), neutral detergent fiber (NDF), and acid detergent fiber (ADF). Regardless of probiotic supplementation, the nitrogen intake and fecal nitrogen levels of animals fed HCT were lower than those fed LCT (P 0.05). Additionally, feeding probiotics increased (P 0.05) the efficiency of ruminal fermentation, final body weight, and average daily gain (ADG) of animals, with this effect being stronger in animals fed HCT. In conclusion, supplementing probiotics with HCT has a positive effect on the growth of finishing beef cattle, thereby providing economic benefits.

The advection–diffusion–Langmuir adsorption processes of a liquid solution, colloid, or suspension occur in many biomedical and chemical engineering fields. The dynamics of the system can be described by the so-called advection–diffusion–reaction (ADR) equations and are greatly influenced by five nondimensional numbers. Up to now, cases over a wider range of parameters have not been thoroughly studied, and the quantitative dependence of the system dynamics on the parameters remains unclear. In this study, we systematically solve the ADR equations in two-dimensional plane Poiseuille flows for cases with selected values of parameters by the finite difference method. We identify two different regimes in terms of the distribution of the maximum adsorption flux and discuss the dominant mechanism of mass transfer and the influences of the nondimensional parameters in each regime. We then propose analytical models to describe the influences of specific parameters on the adsorption equilibrium time. The results of this research may provide a convenient method to identify the dominant processes in the advection–diffusion–Langmuir adsorption system in future studies.

Atrial natriuretic peptide (ANP) is an important hormone in cardiovascular biology. It is activated by the protease corin. In pregnancy, ANP and corin promote uterine spiral artery remodeling, but the underlying mechanism remains unknown. Here we report an ANP function in uterine decidualization and TNF-related apoptosis-inducing ligand-dependent (TRAIL-dependent) death in spiral arterial smooth muscle cells (SMCs) and endothelial cells (ECs). In ANP- or corin-deficient mice, uterine decidualization markers and TRAIL expression were decreased, whereas in cultured human endometrial stromal cells (HESCs), ANP increased decidualization and TRAIL expression. In uterine spiral arteries from pregnant wild-type mice, SMC and EC loss occurred sequentially before trophoblast invasion. In culture, TRAIL from decidualized HESCs induced apoptosis in uterine SMCs, but not in ECs with low TRAIL receptor expression. Subsequently, cyclophilin B was identified from apoptotic SMCs that upregulated endothelial TRAIL receptor and caused apoptosis in ECs. These results indicate that ANP promotes decidualization and TRAIL expression in endometrial stromal cells, contributing to sequential events in remodeling of spiral arteries, including SMC death and cyclophilin B release, which in turn induces TRAIL receptor expression and apoptosis in ECs.

There is a limitation in the process of acoustic signal detection, which lies in serious background noise interference and the complex correlation between acoustic signal characteristics and operation states. Integrating the denoising model and feature classification model, a method of transformer acoustic signal anti-interference detection and operation state detection based on deep learning is proposed in this paper. Through tests in anechoic rooms, acoustic signals of transformers in the normal state or under harmonic load are acquired. Combining these signals with the background noise, a dataset containing 12000 samples of acoustic signals is constructed. To implement anti-interference detection, Conv-TasNet is utilized to get the transformer acoustic signal and environmental noise separated; then, ResNet is utilized to classify the operation states of the transformer accurately. Results show that compared with the blind source separation method through RNN and FastICA, the denoising model established in this paper improves Si-SDRi parameters by 37.4dB and 17.53dB respectively, and the transformer operation state classification model established in this paper classifies the test dataset with an accuracy of 97.7%, thus providing an effective method for the extraction of transformer acoustic signal and diagnosis of transformer operation states in complex environments.

Transmembrane protease serine 2 (TMPRSS2) is a membrane-bound protease expressed in many human epithelial tissues, including the airway and lung. TMPRSS2-mediated cleavage of viral spike protein is a key mechanism in severe acute respiratory syndrome coronavirus 2 activation and host cell entry. To date, the cellular mechanisms that regulate TMPRSS2 activity and cell surface expression are not fully characterized. In this study, we examined two major post-translational events, zymogen activation and N-glycosylation, in human TMPRSS2. In experiments with human embryonic kidney 293, bronchial epithelial 16HBE, and lung alveolar epithelial A549 cells, we found that TMPRSS2 was activated via intracellular autocatalysis and that this process was blocked in the presence of hepatocyte growth factor activator inhibitors 1 and 2. By glycosidase digestion and site-directed mutagenesis, we showed that human TMPRSS2 was N-glycosylated. N-glycosylation at an evolutionarily conserved site in the scavenger receptor cysteine-rich domain was required for calnexin-assisted protein folding in the endoplasmic reticulum and subsequent intracellular trafficking, zymogen activation, and cell surface expression. Moreover, we showed that TMPRSS2 cleaved severe acute respiratory syndrome coronavirus 2 spike protein intracellularly in human embryonic kidney 293 cells. These results provide new insights into the cellular mechanism in regulating TMPRSS2 biosynthesis and function. Our findings should help to understand the role of TMPRSS2 in major respiratory viral diseases.

The MYB transcription factors (TFs) are evolving as critical role in the regulation of the phenylpropanoid and tanshinones biosynthetic pathway. MYB TFs relate to a very important gene family, which are involved in the regulation of primary and secondary metabolisms, terpenoids, bioactive compounds, plant defense against various stresses and cell morphology. R2R3 MYB TFs contained a conserved N-terminal domain, but the domain at C-terminal sorts them different regarding their structures and functions. MYB TFs suppressors generally possess particular repressive motifs, such as pdLNLD/ELxiG/S and TLLLFR, which contribute to their suppression role through a diversity of complex regulatory mechanisms. A novel flower specific “NF/YWSV/MEDF/LW” conserved motif has a great potential to understand the mechanisms of flower development. In the current review, we summarize recent advanced progress of MYB TFs on transcription regulation, posttranscriptional, microRNA, conserved motif and propose directions to future prospective research. We further suggest there should be more focus on the investigation for the role of MYB TFs in microalgae, which has great potential for heterologous protein expression system for future perspectives.

Introduction Myocardial bridging (MB) is a common and usually benign inborn coronary abnormality that may lead to anginal symptoms, acute coronary syndrome, arrhythmias, and rarely sudden cardiac death. MB are most commonly localized in the middle segment of the left anterior descending coronary artery (LAD). The treatment of LAD-MB is still challenging. Our objective was to assess the short- and long-term results of surgical procedures in patients with LAD-MB who had chest pain refractory to medical therapy. Methods Between March 2005 and January 2020, 26 patients (19 males and 7 females; mean 55.8 ± 12.4 years) with MB underwent surgery. All MB was located in the mid-segment of the LAD with a mean length of 4.2 ± 1.7 cm. Coronary angiography before surgery demonstrated LAD-MB with systolic compression more than or equal to 70% in all patients. Results Twenty-five patients underwent myotomy and one patient underwent coronary artery bypass grafting (CABG). All patients survived and recovered uneventfully. Neither hospital or late death nor major complications occurred. Follow-up time was 3-173 months (mean 55.7 months). Follow-up of coronary angiography or computed tomography scan performed in 16 patients demonstrated restoration of coronary blood flow and myocardial perfusion without significant residual compression of the artery. All patients were symptom-free and are currently in NYHA Class I. Conclusion The symptomatic LAD-MB patients who are refractory to medication should actively undergo the surgical intervention such as myotomy and CABG to eliminate the clinical symptoms and achieve satisfactory results by follow-up findings. Myotomy is a preferred procedure because of its safety and satisfactory results.

Centrifugal blood pumps have provided a powerful artificial support system for patients with vascular diseases. In the design process, geometrical optimization is usually needed to acquire a more biocompatible model for clinical uses. In the current paper, we propose a method for multi-objective optimization concerning both the hydraulic and the hemolytic performances of the pump based on the near-orthogonal array in which the traditional hemolysis index (HI) is replaced with the maximum scalar shear stress criteria to reduce the computation load. The method is demonstrated with the optimization of an extracorporeal centrifugal blood pump with an unshrouded impeller. CFD studies on the original and nine modified pump models are carried out. The calculated hydraulic performances of the optimized model are also compared against the experiments for validation of the numeric method, with an error of 3.6% at the original design point. The resulting blood pump with low maximum scalar shear stress (132.2 Pa) shows a low degree of calculated HI (1.69 × 10−3).