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AbstractWith the continuous maturation of technology and the deepening of human-centered design philosophy, eye tracking technology has gradually been applied in research studies for the optimization of flight deck design in commercial aviation. While these studies have focused solely on Pilot Flying (PF), without considering the visual attention distribution of Pilot Monitoring (PM). The purpose of this study was to analyze and compare the visual attention distribution of PF and PM during different flight phases, providing more comprehensive guidance and optimization suggestion to the flight deck design in commercial aviation. This study was conducted in the A320 full-motion flight simulator, with eye tracking technology recording eye movements of PF and PM in the same flight crew simultaneously. The result showed significant differences in three eye movement metrics between PF and PM, not only throughout the whole common manual circuit but also within specific flight phases. Additionally, the results indicated that in certain flight phases, PF and PM exhibited statistically significant correlations in certain eye movement metrics for specific areas of the flight deck. However, in most other instances, no statistically significant correlations were observed between the eye movement metrics of PF and PM. Therefore, the future design of flight decks may benefit from considering differentiation between PF and PM sides in certain flight phases or areas. Additionally, it can be beneficial to make dynamic adjustments to the current flight deck display and control interface while maintaining the existing layout design. [ABSTRACT FROM AUTHOR]

Cultural tourism development potential (CTDP) is the future value and supporting force of the environmental value, economic and social efficiency, innovation ability and supporting system of cultural tourism. At present, there are few relevant studies on CTDP, but the research results on the tourism development potential of cultural heritage are relatively rich, and the existing evaluation methods lack comprehensiveness, dynamics and visualization. Based on systems theory and sustainable development theory, this article attempts to innovate and collect time series data through the entropy method, multi-index comprehensive evaluation method, spatial kernel density estimation method, and centroid transferring model. The temporal and spatial evolution characteristics and the CTDP of 43 cities in the middle and lower reaches of the Yellow River are examined and analyzed. It is found that the CTDP in the middle and lower reaches of the Yellow River is divided into five levels; the overall potential intensity of the research area is small and has significant spatial differences; influenced by the time factor, the interaction and spatial correlation of within the research area are significant; the development of regional cultural tourism has strong regional dependence in the short range. The center of potential gradually moves to the geometric center. This study is significant for promoting the sustainable development of economic tourism in cradles of world civilization.

Abstract Background Circular RNAs (circRNAs) are a group of noncoding RNAs that participate in gene expression regulation in various pathways. The essential roles of circRNAs have been revealed in many species. However, knowledge of circRNAs in fungi is still not comprehensive. Results Trichophyton rubrum (T. rubrum) is considered a model organism of human pathogenic filamentous fungi and dermatophytes. In this study, we performed a genome-wide investigation of circRNAs in T. rubrum based on high-throughput sequencing and ultimately identified 4254 circRNAs. Most of these circRNAs were specific to the conidial or mycelial stage, revealing a developmental stage-specific expression pattern. In addition, 940 circRNAs were significantly differentially expressed between the conidial and mycelial stages. PCR experiments conducted on seven randomly selected differentially expressed (DE-) circRNAs confirmed the circularized structures and relative expression levels of these circRNAs. Based on their genome locations, most circRNAs originated from intergenic regions, unlike those in plants and animals. Furthermore, we constructed circRNA-miRNA-mRNA regulatory networks that included 661 DE-circRNAs targeting 140 miRNAs and further regulating 2753 mRNAs. The relative expression levels of two randomly selected circRNA-miRNA-mRNA axes were investigated by qRT-PCR, and the competing endogenous RNA (ceRNA) network theory was validated. Functional enrichment analysis of the target genes suggested that they were significantly involved in posttranscriptional processes and protein synthesis as well as some small-molecule metabolism processes. CircRNAs are relatively more conserved in closely related dermatophytes but rarely conserved in distantly related species. Tru_circ07138_001 is a highly conserved circRNA that was conserved in all ten dermatophytes analyzed in our study and three distantly related species. Its host gene TERG_07138 was also highly conserved in two of these distantly related species Gallus gallus and Caenorhabditis elegans. The specific role of this circRNA deserves further exploration. Conclusions Our study is the first to provide a global profile of circRNAs in T. rubrum as well as dermatophytes. These results could serve as valuable resources for research on circRNA regulatory mechanisms in fungi and reveal new insights for further investigation of the physical characteristics of these significant human fungal pathogens.

Abstract Treatment with Menin inhibitor (MI) disrupts the interaction between Menin and MLL1 or MLL1-fusion protein (FP), inhibits HOXA9/MEIS1, induces differentiation and loss of survival of AML harboring MLL1 re-arrangement (r) and FP, or expressing mutant (mt)-NPM1. Following MI treatment, although clinical responses are common, the majority of patients with AML with MLL1-r or mt-NPM1 succumb to their disease. Pre-clinical studies presented here demonstrate that genetic knockout or degradation of Menin or treatment with the MI SNDX-50469 reduces MLL1/MLL1-FP targets, associated with MI-induced differentiation and loss of viability. MI treatment also attenuates BCL2 and CDK6 levels. Co-treatment with SNDX-50469 and BCL2 inhibitor (venetoclax), or CDK6 inhibitor (abemaciclib) induces synergistic lethality in cell lines and patient-derived AML cells harboring MLL1-r or mtNPM1. Combined therapy with SNDX-5613 and venetoclax exerts superior in vivo efficacy in a cell line or PD AML cell xenografts harboring MLL1-r or mt-NPM1. Synergy with the MI-based combinations is preserved against MLL1-r AML cells expressing FLT3 mutation, also CRISPR-edited to introduce mtTP53. These findings highlight the promise of clinically testing these MI-based combinations against AML harboring MLL1-r or mtNPM1.

Abstract Silicon is expected to become the ideal anode material for the next generation of high energy density lithium battery because of its high theoretical capacity (4200 mAh g−1). However, for silicon electrodes, the initial coulombic efficiency (ICE) is low and the volume of the electrode changes by over 300% after lithiation. The capacity of the silicon electrode decreases rapidly during cycling, hindering the practical application. In this work, a slidable and highly ionic conductive flexible polymer binder with a specific single‐ion structure (abbreviated as SSIP) is presented in which polyrotaxane acts as a dynamic crosslinker. The ionic conducting network is expected to reduce the overall resistance, improve ICE and stabilize the electrode interface. Furthermore, the introduction of slidable polyrotaxane increases the reversible dynamics of the binder and improves the long‐term cycling stability and rate performance. The silicon anode based on SSIP provides a discharge capacity of ≈1650 mAh g−1 after 400 cycles at 0.5C with a high ICE of upto 92.0%. Additionally, the electrode still exhibits a high ICE of 87.5% with an ultra‐high Si loading of 3.84 mg cm−2 and maintains a satisfying areal capacity of 5.9 mAh cm−2 after 50 cycles, exhibiting the potential application of SSIP in silicon‐based anodes.

BackgroundAtrial fibrillation (AF) is an age-related disease, while telomeres play a central role in aging. But the relationship between AF and telomere length (LTL) is still controversial. This study aims to examine the potential causal association between AF and LTL by using Mendelian randomization (MR).MethodsBidirectional two-sample MR, expression and protein quantitative trait loci (eQTL and pQTL)-based MR were performed using genetic variants from United Kingdom Biobank, FinnGen, and a meta-analysis study, which comprised nearly 1 million participants in the Atrial Fibrillation Study and 470,000 participants in the Telomere Length Study. Apart from the inverse variance weighted (IVW) approach as the main MR analysis, complementary analysis approaches and sensitivity analysis were applied.ResultsThe forward MR revealed a significant causal estimate for the genetically predicted AF with LTL shortening [IVW: odds ratio (OR) = 0.989, p = 0.007; eQTL-IVW: OR = 0.988, p = 0.005; pQTL-IVW: OR = 0.975, p

Artemisinin, an antimalarial traditional Chinese herb, is isolated from Artemisia annua. L, and has shown fewer side effects. Several pieces of evidence have demonstrated that artemisinin and its derivatives exhibited therapeutic effects on diseases like malaria, cancer, immune disorders, and inflammatory diseases. Additionally, the antimalarial drugs demonstrated antioxidant and anti-inflammatory activities, regulating the immune system and autophagy and modulating glycolipid metabolism properties, suggesting an alternative for managing kidney disease. This review assessed the pharmacological activities of artemisinin. It summarized the critical outcomes and probable mechanism of artemisinins in treating kidney diseases, including inflammatory, oxidative stress, autophagy, mitochondrial homeostasis, endoplasmic reticulum stress, glycolipid metabolism, insulin resistance, diabetic nephropathy, lupus nephritis, membranous nephropathy, IgA nephropathy, and acute kidney injury, suggesting the therapeutic potential of artemisinin and its derivatives in managing kidney diseases, especially the podocyte-associated kidney diseases.

Bat coronavirus RaTG13 shares about 96.2% nucleotide sequence identity with that of SARS-CoV-2 and uses human and Rhinolophus affinis (Ra) angiotensin-converting enzyme 2 (ACE2) as entry receptors. Whether there are bat species other than R. affinis susceptible to RaTG13 infection remains elusive. Here, we show that, among 18 different bat ACE2s tested, only RaACE2 is highly susceptible to transduction by RaTG13 S pseudovirions, indicating that the bat species harboring RaTG13 might be very limited. RaACE2 has seven polymorphic variants, RA-01 to RA-07, and they show different susceptibilities to RaTG13 S pseudovirions transduction. Sequence and mutagenesis analyses reveal that residues 34, 38, and 83 in RaACE2 might play critical roles in interaction with the RaTG13 S protein. Of note, RaACE2 polymorphisms have minimal effect on S proteins of SARS-CoV-2 and several SARS-CoV-2 related CoVs (SC2r-CoVs) including BANAL-20-52 and BANAL-20-236 in terms of binding, membrane fusion, and pseudovirus entry. Further mutagenesis analyses identify residues 501 and 505 in S proteins critical for the recognition of different RaACE2 variants and pangolin ACE2 (pACE2), indicating that RaTG13 might have not been well adapted to R. affinis bats. While single D501N and H505Y changes in RaTG13 S protein significantly enhance the infectivity and minimize the difference in susceptibility among different RaACE2 variants, an N501D substitution in SARS-CoV-2 S protein displays marked disparity in transduction efficiencies among RaACE2 variants with a significant reduction in infectivity on several RaACE2 variants. Finally, a T372A substitution in RaTG13 S protein not only significantly increases infectivity on all RaACE2 variants, but also markedly enhances entry on several bat ACE2s including R. sinicus YN, R. pearsonii, and R. ferrumeiqunum. However, the T372A mutant is about 4-fold more sensitive to neutralizing sera from mice immunized with BANAL-20-52 S, suggesting that the better immune evasion ability of T372 over A372 might contribute to the natural selective advantage of T372 over A372 among bat CoVs. Together, our study aids a better understanding of coronavirus entry, vaccine design, and evolution.

Sterol 14α-demethylase catalyzes lanosterol hydroxylation, which is one of the key reactions in the biosynthetic pathway of sterols. There is only one sterol 14α-demethylases gene named Erg11 in Saccharomyces cerevisiae genome. In this study, three sterol 14α-demethylases genes named AoErg11A, AoErg11B and AoErg11C were identified in Aspergillus oryzae genome through bioinformatics analysis. The function of these three genes were studied by yeast complementation, and the expression pattern/subcellular localization of these genes/proteins were detected. The results showed that the three AoErg11s were expressed differently at different growth times and under different abiotic stresses. All of the three proteins were located in endoplasmic reticulum. The AoErg11s could not restore the temperature-sensitive phenotype of S. cerevisiae erg11 mutant. Overexpression of the three AoErg11s affected both growth and sporulation, which may be due to the effect of AoErg11s on ergosterol content. Therefore, this study revealed the functions of three AoErg11s and their effects on the growth and ergosterol biosynthesis of A. oryzae, which may contribute to the further understanding of the ergosterol biosynthesis and regulation mechanism in this important filamentous fungus, A. oryzae.

BackgroundThere are controversies on the pathophysiological alteration in patients with atrial fibrillation (AF) undergoing pulmonary vein isolation using different energy sources.ObjectivesWe evaluated the changes in plasma proteins in acute phase post-ablation in patients receiving cryoballoon ablation, radiofrequency balloon ablation, or radiofrequency ablation.MethodsBlood samples from eight healthy controls and 24 patients with AF were taken on the day of admission, day 1, and day 2 post-ablation and analyzed by the Olink proximity extension assay. Proteins were identified and performed with enrichment analysis. Protein–protein interaction network and module analysis were conducted using Cytoscape software.ResultsOf 181 proteins, 42 proteins in the cryoballoon group, 46 proteins in the radiofrequency balloon group, and 43 proteins in the radiofrequency group significantly changed after ablation. Most of the proteins altered significantly on the first day after ablation. Altered proteins were mainly involved in cytokine–cytokine receptor interaction. Both balloon-based ablations showed a similar shift toward enhancing cell communication and regulation of signaling while inhibiting neutrophil chemotaxis. However, radiofrequency ablation presented a different trend. Seed proteins, including osteopontin, interleukin-6, interleukin-10, C-C motif ligand 8, and matrix metalloproteinase-1, were identified. More significant proteins associated with hemorrhage and coagulation were selected in balloon-based ablations by machine learning.ConclusionPlasma protein response after three different ablations in patients with AF mainly occurred on the first day. Radiofrequency balloon ablation shared similar alteration in protein profile as cryoballoon ablation compared with radiofrequency ablation, suggesting that lesion size rather than energy source is the determinant in pathophysiological responses to the ablation.

Abstract Background Human epidermal growth factor receptor2+ subtype breast cancer has a high degree of malignancy and a poor prognosis. The aim of this study is to develop a prediction model for the human epidermal growth factor receptor2+ subtype (non-luminal) of breast cancer based on the clinical and ultrasound features related with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor2. Methods We collected clinical data and reviewed preoperative ultrasound images of enrolled breast cancers from September 2017 to August 2020. We divided the data into in three groups as follows. Group I: estrogen receptor ± , Group II: progesterone receptor ± and Group III: human epidermal growth factor receptor2 ± . Univariate and multivariate logistic regression analyses were used to analyze the clinical and ultrasound features related with biomarkers among these groups. A model to predict human epidermal growth factor receptor2+ subtype was then developed based on the results of multivariate regression analyses, and the efficacy was evaluated using the area under receiver operating characteristic curve, accuracy, sensitivity, specificity. Results The human epidermal growth factor receptor2+ subtype accounted for 138 cases (11.8%) in the training set and 51 cases (10.1%) in the test set. In the multivariate regression analysis, age ≤ 50 years was an independent predictor of progesterone receptor + (p = 0.007), and posterior enhancement was a negative predictor of progesterone receptor + (p = 0.013) in Group II; palpable axillary lymph node, round, irregular shape and calcifications were independent predictors of the positivity for human epidermal growth factor receptor-2 in Group III (p = 0.001, p = 0.007, p = 0.010, p

ABSTRACT Screening for active tuberculosis (TB) among individuals with latent tuberculosis infection (LTBI) is important for the initiation and evaluation of TB preventive treatment. The performances of different tools and their combinations had rarely been studied in community-level screening among individuals with LTBI in China. This study aimed to explore appropriate algorithms for screening for active TB among individuals with LTBI in rural China. Three sputum samples were collected from each participant for smear microscopy, culture, and an Xpert MTB/RIF assay. Chest digital radiography and TB symptoms were investigated as well. The performances of different testing algorithms were compared with that of sputum culture as the gold standard. Overall, 1,564 study participants with LTBI were investigated, with a final diagnosis of 20 TB cases by sputum culture. Compared with other tests, the Xpert MTB/RIF assay detected 80.00% (95% confidence interval [CI], 58.40% to 91.93%) of culture-positive cases, with the highest sensitivity. When tests were combined using “or,” “and,” or “step” algorithms, the highest sensitivity reached 90.00% (95% CI, 69.90% to 97.21%) for the combination of the Xpert MTB/RIF assay and chest radiography, but the positive predictive value (PPV) decreased to 22.22% (95% CI, 14.54% to 32.41%). The Xpert MTB/RIF assay alone showed the best agreement with sputum culture, with a kappa value of 0.840. Pathogen molecular detection alone showed good performance compared to the other algorithms, for ruling out active TB in general LTBI, but the high cost might be a challenge for scaling it up. Identifying those with a high risk for progression to TB more precisely and establishing a cost-effective screening algorithm deserve further exploration. IMPORTANCE Enhancing community-wide active case screening in target LTBI populations is important for achieving the early treatment of active TB, and ruling active TB out is a prerequisite for initiating preventive treatment. The current study evaluated the performances of multiple tests and their combinations in screening for active TB among individuals with LTBI at the community level. Compared with the classical “TB symptoms and chest radiography” algorithm, the application of Xpert MTB/RIF improved the sensitivity from 45% to 80%. When the Xpert MTB/RIF assay was combined with chest radiography, the sensitivity was further improved to 90.00%, which achieved the World Health Organization (WHO) target product profiles. However, the algorithm requires caution as the PPV decreased from 88.89% for Xpert MTB/RIF alone to 22.22% for the combination. Xpert MTB/RIF alone offered remarkable sensitivity without compromising the PPV but would have major resource implications. Thus, identifying target populations for LTBI treatment more precisely and developing cost-effective and high-throughput screening tools and algorithms deserve further efforts.

Abstract Objective Obstructive sleep apnoea (OSA) is one cause of pulmonary hypertension (PH) and can also emerge along with PH. The clinical diagnosis and treatment of OSA in patients with PH are still controversial. The purpose of this clinical observation study was to observe and summarize the incidence and clinical characteristics of OSA in patients with PH and to explore possible predictors of PH combined with OSA. Methods Patients with PH diagnosed by right heart catheterization who underwent overnight cardiorespiratory monitoring from December 2018 to December 2020 were enrolled. OSA was defined as an apnoea–hypopnoea index of ≥ 5/h with ≥ 50% of apnoeic events being obstructive. Baseline clinical characteristics and parameters were collected to compare PH patients with and without OSA. Logistic regression analysis was run to determine the risk factors for OSA in PH patients. Results A total of 35 (25%) of 140 patients had OSA. OSA is relatively frequent in patients with PH, especially in patients with chronic thromboembolic pulmonary hypertension and patients with lung disease– or hypoxia-associated PH. The patients who had OSA were mostly male and had a higher age and a lower daytime arterial oxygen pressure. Logistic regression analysis found that older age, male sex, and lower daytime arterial blood oxygen pressure correlated with OSA in PH patients. Conclusion OSA is common in patients with PH. Lower daytime arterial oxygen pressure is a risk factor for OSA in older male patients with PH.

AIM:To compare the effect of self-crosslinking sodium hyaluronic gel, Nasopore, and gelatin sponge in endonasal endoscopic dacryocystorhinostomy(En-DCR).METHODS:Totally 72 patients(90 eyes)of chronic dacryocystitis admitted to our hospital from June 2019 to June 2020, and randomly divide them into three groups. Self-crosslinking sodium hyaluronic gel(group A), Nasopore(group B), and gelfoam(group C)were used during the En-DCR. Comfort level, bleeding, complication and epiphora, lacrimal situation were observed 2wk, 1, 2, 3, 6mo after surgery. Comparison of cure rate and effective rate.RESULTS: The patients were followed up for 6mo after operation. The cure rate of lacrimal system reconstruction was 97% in group A, 89% in group B and 94% in group C. There was no meaningful statistical difference among the three groups(P>0.05). The effective rate of lacrimal system reconstruction was 91% in group A, 56% in group B and 87% in group C(P0.0167). Postoperative comfort level was better and bleeding was more severe in the group of A than in group B(P

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important and major player in the pathophysiology of hypercholesterolemia and atherosclerosis. Recently, PCSK9 has been implicated in the pathogenesis of inflammatory diseases. Whether PCSK9 is involved in idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to investigate the relationship between PCSK9 and IPAH. Serum PCSK9, interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), interleukin‐1 β (IL‐1β), and monocyte chemotactic protein‐1 (MCP‐1) were measured by enzyme linked immunosorbent assay. Transthoracic echocardiography was performed among 40 IPAH patients and 20 control subjects. Hemodynamic data were collected via right heart catheterization in patients with IPAH. Serum PCSK9, TNF‐α, IL‐6, IL‐1β, and MCP‐1 levels were significantly higher in IPAH patients than in control subjects (p

The application of materials with special wettability is a hot research topic in recent years. It is reported that Bi2O3 coating with hydrophobic modification could achieve the reversible conversion of superhydrophobicity to superhydrophilicity under UV-visible light irradiation and dark storage. Based on this finding, the application of Bi2O3 coating in antibacterial and oil-water separation under different wettability was studied. The results show that superhydrophobic surface exhibits good bacterial anti-adhesion effect against E.coli and S.aureus, while superhydrophilic surface shows selectively antibacterial activity. In terms of oil-water separation, the superhydrophobic surface can block water and allow oil pass through the filter with the separation efficiency more than 93%, while the superhydrophilic surface can block oil and allow water pass through the filter after pre-wetting treatment. Therefore, Bi2O3 coating with reversible wettability can be used as an intelligent antibacterial membrane material for oil-water separation, which has potential application in the field of oil-water separation.

To solve the problem of mode competition in high-order working modes, this paper presents a fast design method based on the TM31-2π mode for the dumbbell shaped extended interaction cavity. Based on the equivalent circuit theory, the high-frequency characteristics of the structure are studied. In addition, we propose a W-band continuous wave sheet beam extended interaction klystron high-frequency circuit. The circuit was driven by a 20 kV and 0.85 A sheet electron beam, with a 3.2 × 0.3 mm2 section. The beam was focused by a 0.8 T permanent magnet system. The high-frequency system adopts five dumbbell shaped five-gap cavities, and the output system adopts a symmetrical output waveguide. The 3D particle-in-cell simulation shows that more than 1.5 kW power can be obtained at an input power of 0.12 W, and the electron efficiency and gain are 9.2% and 41.2 dB, respectively.

Background: To achieve favorable hemodynamics, the number of balloon pulmonary angioplasty (BPA) sessions varied significantly among patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Increased BPA sessions burdened patients financially and psychologically. We aim to identify baseline characteristics that could predict early BPA response. Methods: Consecutive patients who were diagnosed with inoperable CTEPH and received BPA between May 2018 and October 2021 at Fuwai Hospital were retrospectively collected. Patients were categorized into ‘Early BPA responders’ or ‘Non-early BPA responders’ according to the hemodynamic outcome within the first three BPA sessions. Results: In total, 101 patients were included into analysis. At baseline, non-early BPA responders had lower female proportion, longer disease duration, and poorer laboratory test results compared with early responders, whereas hemodynamics were comparable. After the first three BPA sessions, hemodynamic improvement was more significant in early responders. Incidence of complication was comparable between the two groups. Multivariable logistic analysis identified that female sex (odds ratio [OR]: 7.155, 95% confidence interval [CI]: 1.323-38.692, p = 0.022), disease duration (OR: 0.851, 95% CI: 0.727-0.995, p = 0.043), baseline total bilirubin (OR: 0.934, 95% CI: 0.875-0.996, p = 0.038), and baseline NT-proBNP (OR: 0.473, 95% CI: 0.255-0.879, p = 0.018) were independently associated with early BPA response. Combination of these four parameters could predict 90% early BPA response. Conclusions: Patients with shorter disease duration, female sex, lower baseline NT-proBNP, and lower baseline total bilirubin are more likely to achieve early hemodynamic response to BPA. Moreover, early hemodynamic response was not accompanied with increased incidence of procedure-related complications.