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Higher risk for influenza-associated pulmonary aspergillosis (IAPA) in asthmatic pati...
Frederike Waldeck
Filippo Boroli

Frederike Waldeck

and 16 more

September 02, 2022
Background: Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. Methods: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/18 and 2019/20 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24h were included. IAPA was diagnosed according to previously published clinical, radiological and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome which was a composite of in-hospital mortality, ICU length of stay ≥7d, mechanical ventilation ≥7d or extracorporeal membrane oxygenation. Results: 158 patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, p=0.05). Asthma (OR 12.0 (95% CI 2.1-67.2)) and days of mechanical ventilation (OR 1.1 (1.1 – 1.2)) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, p=0.001) and vasoactive support (75% vs. 45%, p=0.03) and had more complications including ARDS (53% vs. 26%, p=0.04), respiratory bacterial infections (65% vs. 37%, p=0.04) and higher ICU-mortality (35% vs. 16.4%, p=0.05). IAPA (OR 28.8 (3.3–253.4)), influenza A (OR 3.3 (1.4-7.8)) and higher SAPS II score (OR 1.07 (1.05—1.10)) were independent predictors of poor outcome. Interpretation: High clinical suspicion, early diagnostics and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.
A First Principles Study of Nonlinear Optical Properties of a Quinoline Derivative
Renato  Medeiros
Clodoaldo Valverde

Renato Medeiros

and 4 more

September 02, 2022
A quinoline derivative, 4-(quinolin-2-ylmethylene)aminophenol was synthesized and structurally characterized by single crystal X-ray diffraction. The crystal packing behaviour and intermolecular interactions were examined by Hirshfeld surface analyses, 2D fingerprint plots and QTAIM analysis. The second order nonlinear response of 4-(quinolin-2-ylmethylene)aminophenol molecule immersed in DMSO was investigated at PCM/DFT/CAM-B3LYP/6-311++G(d,p) level. Theoretical calculations of the Hyper-Rayleigh scattering first hyperpolarizability were performed using two different procedures, the Sum-over-states scheme and the energy derivative method from Gaussian16. The HRS first hyperpolarizability results were compared with obtained for other organic compounds and shown that the 4-(quinolin-2-ylmethylene)aminophenol presents a good nonlinear optical response.
Population Genetics of Parasites and Their Arthropod Hosts
Kateřina Bezányiová
Jakub Straka

Kateřina Bezányiová

and 1 more

January 18, 2023
In comparison to organisms parasitising vertebrates, parasites of arthropods are direly understudied despite their abundance, importance, and potential usefulness. Due to their close relationship and coevolution with the host, parasites can be used as tools allowing the inference of information on host life history, ecology, and past events the host species has experienced. Even though parasites comprise a diverse assemblage of taxa, it is possible to identify convergent patterns in their genetic population structure. Predictions of congruent population genetic co-structuring between hosts and parasites can be thus based on a few traits such as host specificity, life cycle complexity or parasite and/or host dispersal. The parasite may even provide better resolution of population structure than the host itself, serving as a proxy that can be used to direct conservation projects of both the host and parasite. Our review provides an overview of known cases of host-parasite population co-structuring in arthropods, identifies their common patterns, and discusses practical applications of these findings.
Characterization of the endogenous promoters in Yarrowia lipolytica for the biomanufa...
Chang Wang
Xueyao Lu

Chang Wang

and 7 more

September 02, 2022
Yarrowia lipolytica, an oleaginous yeast with the GRAS status, has been developed as a platform for the chemical production. Specifically, promoter engineering is an important approach to regulating gene expression at the transcriptional level, which is of great significance in constructing microbial cell factories. Until now, some work on the promoter study has been carried out in Y. lipolytica. However, compared with other microorganisms, such as Saccharomyces cerevisiae, Bacillus subtilis, and etc., obtained achievements still need further replenishment and development for Y. lipolytica. For this, we screened 81 endogenous promoters in Y. lipolytica, mainly involved in carbon metabolism, amino acid metabolism, and lipid metabolism. As a result, we obtained 15 strong promoters, 41 medium strength promoters, and 25 weak promoters, with the strength spanning from 0.06% to 1.60-fold of PTEF promoter. In general, our study provides a unique and available endogenous promoter library for Y. lipolytica.
The Work Architecture of the Sears List of Subject Headings (SLSH), Library of Congre...
Subhajit Panda

Subhajit Panda

September 02, 2022
A document by Subhajit Panda. Click on the document to view its contents.
Potential for significant precipitation cycling by forest-floor litter and deadwood
Marius G. Floriancic
Scott Allen

Marius G. Floriancic

and 5 more

October 26, 2022
The forest-floor litter layer can retain substantial volumes of water, thus affecting evaporation and soil-moisture dynamics. However, litter layer wetting/drying dynamics are often overlooked when estimating forest water budgets. Here we present field and laboratory experiments characterizing water cycling in the forest-floor litter layer, and outline its implications for subcanopy microclimatic conditions and for estimates of transpiration and recharge. Storage capacities of spruce needle litter and beech broadleaf litter averaged 3.1 mm and 1.9 mm respectively, with drainage/evaporation timescales exceeding 2 days. Litter-removal experiments showed that litter reduced soil water recharge, reduced soil evaporation rates, and insulated against ground heat fluxes that impacted snowmelt. Deadwood stored ~0.7 mm of water, increasing with more advanced states of decomposition, and retained water for >7 days. Observed daily cycles in deadwood weight revealed decreasing water storage during daytime as evaporation progressed and increasing storage at night from condensation or absorption. Water evaporating from the forest-floor litter layer modulates the subcanopy microclimate by increasing humidity, decreasing temperature and reducing VPD. Despite the relatively small litter storage capacity (<3.1 mm in comparison to ~10 2 mm for typical forest soil rooting zones) the litter layer alone retained and cycled 18% of annual precipitation, or 1/3 of annual evapotranspiration. These results suggest that overlooking litter interception may lead to substantial overestimates of recharge and transpiration in many forest ecosystems.
A nonuniform mesh method in the Floquet parameter domain for wave scattered by period...
Ruming  Zhang
Tilo Arens

Ruming Zhang

and 1 more

September 02, 2022
In this paper, we propose a new nonuniform mesh method to simulate acoustic scattering problems in two dimensional periodic structures with non-periodic incident fields numerically. As existing methods are difficult to extend to higher dimensions, we have designed the new method with such extensions in mind. With the help of the Floquet-Bloch transform, the solution to the original scattering problem is written as an integral of a family of quasi-periodic problems. These are defined in bounded domains for each value of the Floquet parameter which varies in a bounded interval. The key step in our method is the numerical approximation of the integral by a quadrature rule adapted to the regularity of the family of quasi-periodic solutions. We design a nonuniform mesh with a Gaussian quadrature rule applied on each subinterval. We prove that the numerical method converges exponentially with respect to both the number of subintervals and the number of Gaussian quadrature points. Some numerical experiments are provided to illustrate the results.
A Segmented Filtering Method of Anti Interrupted Sampling Jamming
mengfei liu
Jiyuan Chen

mengfei liu

and 3 more

September 02, 2022
Interrupted-sampling jamming (ISJ) is a big threat to large time-band width radar. In order to enhance anti-jamming capability of radar, it is a key problem to filter the jamming without harm to target information. To solve the problem, this letter proposes a new method to filter the jamming by designing filers dividedly after estimating the ISJ parameters. The filters change the state of jamming and make it fused with the echo. Experiments show that this method can divide the jamming and echo. The reduction of ISJ is about 6dB
Characterizations and representations of Hilbert-Schmidt frames in Hilbert spaces
Yan-Ling Fu
Wei Zhang

Yan-Ling Fu

and 1 more

September 02, 2022
Hilbert-Schmidt frame(HS-frame) is essentially an operator-valued frame, it is more general than g-frames, and thus, covers some generalizations of frames. This paper addresses the Hilbert-Schmidt frames theory for Hilbert spaces. We first introduce the notion of HS-preframe operator, and characterize the HS-frames, Parseval HS-frames, HS-Riesz bases, HS-orthonormal bases and dual HS-frames in terms of HS-preframe operators. In particular, we characterize the dual HS-frames in a constructive way, that is, the algebraic formulae for all dual HS-frames of a given HS-frame are given. Then we discuss the sum of HS-frames through the properties of HS-preframe operators. Finally, we present the representations of HS-frames in terms of linear combinations of simpler ones such as HS-orthonormal bases, HS-Riesz bases and Parseval HS-frames, especially an HS-frame can be represented as a linear combination of two HS-orthonormal bases if and only if it is an HS-Riesz basis.
Assessment tools for monitoring microplastics from surface water bodies: Challenges a...
SMRITY SONBHADRA

Smrity Sonbhadra

and 1 more

September 05, 2022
Smrity Sonbhadra, Lalit M. Pandey*Bio-interface & Environmental Engineering LabDepartment of Biosciences and Bioengineering,Indian Institute of Technology Guwahati, Assam, 781039, India*Corresponding author: Tel. +91-361-258-3201; Fax +91-361-258-2249Email addresses: s.smrity@iitg.ac.in, lalitpandey@iitg.ac.in
NON-ARCHIMEDEAN WELCH BOUNDS AND NON-ARCHIMEDEAN ZAUNER CONJECTU
K. Mahesh Krishna

K. Mahesh Krishna

September 02, 2022
Let K be a non-Archimedean (complete) valued field satisfying n j=1 λ 2 j = max 1≤j≤n |λ j | 2 , ∀λ j ∈ K, 1 ≤ j ≤ n, ∀n ∈ N. For d ∈ N, let K d be the standard d-dimensional non-Archimedean Hilbert space. Let m ∈ N and Sym m (K d) be the non-Archimedean Hilbert space of symmetric m-tensors. We prove the following result. If {τ j } n j=1 is a collection in K d satisfying τ j , τ j = 1 for all 1 ≤ j ≤ n and the operator Sym m (K d) x → n j=1 x, τ ⊗m j τ ⊗m j ∈ Sym m (K d) is diagonalizable, then max 1≤j,k≤n,j =k {|n|, ||τ j , τ k | 2m } ≥ |n| 2 d+m−1 m. (1) We call Inequality (1) as the non-Archimedean version of Welch bounds obtained by Welch [IEEE Transactions on Information Theory, 1974 ]. We formulate non-Archimedean Zauner conjecture.
Hacking Techniques Improve Health and Nutritional Status of Nestling White-tailed Eag...
Miguel Ferrer
Rhian  Evans

Miguel Ferrer

and 8 more

September 01, 2022
Birds of prey frequently feature in reintroductions and the hacking technique is typically used. Hacking involves removing large nestlings from donor populations, transferring them to captivity, feeding them ad libitum. Potentially, via the hacking method, stress of captivity and disruption of parental feeding may be detrimental. Alternatively, provision of ad libitum food may be advantageous. Although hacking has underpinned reintroduction project successes there has been no research on how the method may affect the health and nutritional status of translocated birds during captivity. We compared blood chemistry data from 55 young White-tailed Eagles, translocated from Norway as part of the species’ reintroduction to Scotland, from sampling soon after arriving in captivity and again (≈ 42 d later) before their release. Numerous significant differences between first and second samples were found, but no significant interactions showed that sexes responded similarly to captivity. According to hematological and biochemical metrics, individuals showed several changes during captivity, including in red blood cell parameters, plasma proteins and white cellular parameters related to the immune system, that indicated improved health status. Captivity with ad libitum food was associated with decreased urea and uric acid values: high values can indicate nutritional stress. Urea values became more normally distributed before release, indicating that ad libitum food had reduced nutritional differences between early nestlings in the season and later ones. Despite plentiful food, both sexes lost body mass before release, suggesting an inherent physiological mechanism to improve flight performance in fledglings. We conclude that hacking improved the health and nutritional status of released eagles which is likely to enable birds to cope with greater costs of exploratory behavior which they may require in reintroduction projects. In this context, we note the absence of survival differences between hacked and wild raptors in previous research.
Dimensionless Unification of the Fundamental Interactions
Stergios Pellis

Stergios Pellis

September 02, 2022
 In this paper in an elegant way will be present the simple unification of the fundamental interactions. We will calculate the unity formulas that connect the coupling constants of the fundamental forces. We will find the formulas for the Gravitational constant. It will be presented that the gravitational fine-structure constant is a simple analogy between atomic physics and cosmology. We will find the expression that connects the gravitational fine-structure constant with the four coupling constants. Perhaps the gravitational fine-structure constant is the coupling constant for the fifth force. Also will be presented the simple unification of atomic physics and cosmology. We will find the formulas for the cosmological constant and we will propose a possible solution for the cosmological parameters. Perhaps the shape of the universe is Poincaré dodecahedral space. Finally will be presented the law of the gravitational fine-structure constant followed by ratios of maximum and minimum theoretical values for natural quantities. This article will be followed by the energy wave theory and the fractal space-time theory.
Lancemaside A from Codonopsis lanceolata is a broad-spectrum antiviral agent against...
Tai Young Kim
Sangeun  Jeon

TAI YOUNG KIM

and 7 more

September 01, 2022
Background and Purpose Codonopsis lanceolata (CL) has long been used as a medicinal herb in East Asian countries to treat inflammatory diseases of the respiratory system but its antiviral activity has not been investigated. Here, we evaluated the potential inhibitory activity of CL extracts and their active compounds on SARS-CoV-2. Experimental Approach Pseudotyped SARS-CoV-2 entry assay and dose-response curve analysis with authentic SARS-CoV-2 and recombinant SARS-CoV-2 reporter virus expressing the nanoluciferase were carried out to investigate the effects of compounds against SARS-CoV-2 entry into host cells. Filipin cholesterol staining, SARS-CoV-2 Spike (S)-ACE2 binding assay, and S-mediated cell fusion assay using time-lapse imaging, flow cytometry, and split-GFP fusion were conducted to understand the inhibitory mechanisms. Key Results Lancemaside A (LA), a triterpenoid saponin isolated from CL, impeded the endosomal entry pathway of SARS-CoV-2 and its variants including Alpha, Beta, Delta, and Omicron with similar IC50 values of 2.23 ~ 3.37 μM as well as the TMPRSS2-mediated viral entry pathway with IC50 value of 3.92 μM. LA was also able to prevent the formation of S-induced multinucleated syncytia. Mechanically, LA altered the distribution of host cell membrane cholesterol and blocked the membrane fusion between SARS-CoV-2 and host cells. Conclusion and implications LA can be a broad-spectrum antiviral drug not only against SARS-CoV-2 but also against other novel enveloped viral pathogens that might arise in the future by targeting viral envelope fusion with the host cell membrane. Keywords SARS-CoV-2, Omicron, COVID-19, Lancemaside A, triterpenoid saponin, membrane fusion
Prostaglandin I2 suppresses the development of gut-brain axis disorder in irritable b...
Shima Kumei
Masatomo Ishioh

Shima Kumei

and 3 more

September 01, 2022
Background and Purpose We attempted to clarify a role of prostaglandin (PG) I2 and its specific receptor, IP in the pathogenesis of irritable bowel syndrome (IBS). Experimetal Approach Using a maternal separation (MS)-induced rat IBS model, the effect of IP agonist on the development of IBS phenotype such as visceral hypersentivity and depressive state. To further investigate the mechanisms of IP signaling on IBS phenotypes, serum hormone, metabolites and fecal microbiota were examined. Key Results Administration of beraprost (BPS), a specific IP agonist, improved visceral hypersensitivity and depressive state with decreased serum corticotropin-releasing factor (CRF) level in the IBS rats. In serum metabolome analysis, 1-methylnicotinamide (1-MNA) was identified as a possible candidate for a clue metabolite of pathogenesis of. The serum 1-MNA levels revealed inverse correlation to the level of visceral sensitivity, and positive correlation to a depression marker, immobilizing time. Administration of 1-MNA induced visceral hypersensitivity and depression with increased levels of serum CRF. Fecal microbiota by T-RFLP analysis revealed the proportion of clostridium cluster XI, XⅣa and XVⅢ was significantly changed in MS-induced IBS rats treated with BPS. Fecal microbiota transplant of BPS-treated rats improved visceral hypersensitivity and depression in MS-induced IBS rats. Conclusion and Implication PGI2-IP signaling plays an important role in IBS phenotypes such as visceral hypersensitivity and depressive state. BPS modified microbiota, thereby inhibition of 1-MNA-CRF pathway, followed by improvement of MS-induced IBS phenotype. These results suggest that the PGI2-IP signaling could be considered to be a therapeutic option for IBS.
Pneumonia caused by Scedosporium in non-Transplant and non-HIV-infected adults:A case...
Aixia Wang
Ping Yang

Aixia Wang

and 4 more

September 01, 2022
The lung is one of the most commonly encountered sites of Scedosporium infection. Due to its intrinsic resistance to all current antifungal agents, treatment of Scedosporium infections still remains a great challenge. Voriconazole has been recommended to the first-line systemic treatment of Scedosporium infections, but the duration is not well recommended, especially for immunocompetent patients. This case series presented our experience on diagnostic, manifestation, and treatment strategies of Scedosporium pneumonia. The case records of non-Transplanted non-HIV adults with Scedosporium pneumonia hospitalized in our Hospital from January 2020 to February 2022 were retrospectively analyzed, and their case characteristics, antifungal therapy drug selection and treatment course were summarized: All 3 patients had underlying lung disease, 2 female patients had a history of bronchiectasis, and 1 male patient had a history of emphysema. Both female patients had a mixed infection with Scedosporium and nontuberculous mycobacteria. In one female patients, Scedosporium was no longer detected after 2 months of treatment with voriconazole, and the clinical symptoms were improved than before, with no significant change in imaging. In one female patient, although Scedosporium was still isolated from sputum after 12 months with voriconazole treatment, the symptoms were improved than before, and antifungal therapy was discontinued after no significant improvement 1 and a half months after switching to Posaconazole. In one male patient, Scedosporium was no longer detected after 3 months treatment with voriconazole, and the clinical symptoms and imaging were significantly improved. Three patients had voriconazole concentrations between 1.1-2.8 μg/mL during treatment.
Therapeutic Drug Monitoring of Pregabalin in a critically ill patient with Acute Kidn...
Francesca Di Mario
Eleonora  Galosi

Francesca Di Mario

and 7 more

September 01, 2022
Pregabalin is an anti-epileptic drug which also represents one of the most frequently prescribed medications for neuropathic pain management worldwide. Moreover, in recent years its use has widely increased also in critically ill patients in the setting of multimodal analgesia. Commonly available as capsules and oral solution, it is characterized by a predominant kidney elimination. Consequently, in patients with kidney failure posology adjustments are needed. According to the pharmacokinetic parameters (low molecular weight and volume of distribution, negligible protein binding), pregabalin is expected to undergo a significant extracorporeal clearance, which should be taken into account when one of the different Kidney Replacement Therapy (KRT) modalities is required for Acute Kidney Injury (AKI). The case of a critically ill patient with AKI undergoing Therapeutic Drug Monitoring of Pregabalin in course of Continuous, Prolonged Intermittent KRT (CKRT and PIKRT, respectively), and conventional intermittent hemodialysis (IHD) is presented here for the first time.
Impact of High-Intensity Physical Exercise (28 Consecutive Marathons) on Sleep Qualit...
Gualberto Buela-Casal
Noelia Ruiz-Herrera

Gualberto Buela-Casal

and 5 more

September 01, 2022
The sleep quality and quantity of an athlete who ran 28 consecutive marathons were analysed through three polysomnography sessions to explore the sleep-dependent recovery process. We observed differences in quantity, quality, and sleep distribution in all variables evaluated. In conclusion, high-intensity physical exercise negatively affects sleep without proper recovery.
Limited movement of an avian hybrid zone in relation to regional variation in magnitu...
Alana Alexander
Mark Robbins

Alana Alexander

and 4 more

September 01, 2022
Studies of natural hybrid zones can provide documentation of range shifts in response to climate change and identify loci important to reproductive isolation. Using a deep temporal (36-38 years) comparison of the black-capped (Poecile atricapillus) and Carolina (P. carolinensis) chickadee hybrid zone, we investigated movement of the western portion of the zone (western Missouri) and assessed whether loci and pathways underpinning reproductive isolation were similar to those in the eastern portion of the hybrid zone. Using 92 birds sampled along the hybrid zone transect in 2016 and 68 birds sampled between 1978 and 1980, we generated 11,669 SNPs via ddRADseq. These SNPs were used to assess movement of the hybrid zone through time and to evaluate variation in introgression among loci. We demonstrate that the interface has moved ~5 km to the northwest over the last 36-38 years, i.e., at only one-fifth the rate at which the eastern portion (e.g., Pennsylvania, Ohio) of the hybrid zone has moved. Temperature trends over the last 38 years reveal that eastern areas have warmed 50% more than western areas in terms of annual mean temperature, possibly providing an explanation for the slower movement of the hybrid zone in Missouri. Our results suggest hybrid zone movement in broadly distributed species, such as chickadees, will vary between areas in response to local differences in the impacts of climate change.
Identification and optimization strategy of gully agricultural land and water resourc...
Lulu Qu
Yurui Li

Lulu Qu

and 4 more

September 01, 2022
Gully agricultural land and water resource (GALWR) sustainable utilization in China’s Loess Plateau is vital to the evolution law of human-earth relationship and agricultural multi-functional transformation in the context of green high-quality development. However, characteristics and pattern of GALWR and optimization strategy is still unclear. Here we evaluated the carrying capacity of GALWR in the loess hilly and gully region (LHGR) based on the matter element model. We further investigated driving factors for GALWR sustainable utilization and optimization strategy of the dual guidance of economy and society as well as resources and ecology. The results showed that: (1) The distribution of cultivated land in the LHGR showed strong differences between districts and counties, with more distribution in the middle and less distribution on both sides. The matching degree of GALWR was low, and the elastic sensitivity analysis showed that the per capita water resources, the proportion of primary production, the drought index and the vegetation coverage were the sensitive factors affecting the sustainable utilization of GALWR in the LHGR. (2) There were obvious differences in the coupling and coordination of agricultural GALWR in the LHGR in 2020, and the whole was in the antagonistic coupling stage. (3) There was a lack of synchronization between GALWR utilization. Water resources lagging areas should take water resources adaptive management and the multi-element coupling process of “water-land-climate-crop” to protect gullies, rivers, forests, farmlands and lakes in a coordinated way. Land resources utilization lagging areas should actively explore the main function-oriented zoning, dominant type classification and principal purpose classification optimal strategy of gully land resources in combination with land engineering control measures. This study provides a guideline for the transformation of agriculture and the construction of a new pattern of high-quality agricultural development in the Loess Plateau.
Surface engineering of nanomaterials
Mainak Saha
manab.mme

Mainak Saha

and 1 more

September 02, 2022
Mainak Saha1,21Department of Metallurgical and Materials Engineering, Indian Institute of Technology Madras, Chennai-600036, Tamil Nadu, India2Department of Metallurgical and Materials Engineering, National Institute of Technology Durgapur-713209, West Bengal, IndiaEmail address: mainaksaha1995@gmail.comPhone number: +918017457062Type: Review
Rapid global spread of Variant of Concern of SARS-CoV-2
Daihai He
Benjamin Cowling

Daihai He

and 3 more

September 01, 2022
In this work, we show the spatiotemporal spread and replacement of different Variant of Concern (VOC) of SARS-COV-2. We define a metric to quantify the spread speed of each COV. We discuss the basic reproductive number of these VOC’s and possible impact of travel ban.
Atrial fibroblasts secrete exosomal miR-21 that up-regulates KCa3.1 channels in atria...
Yuntao Fu
Huiyu Chen

Yuntao Fu

and 13 more

September 01, 2022
Background: Fibroblast-derived exosomes can regulate the electrical remodeling of cardiomyocytes, and the KCa3.1 channel is an important factor in atrial electrical remodeling; however, the underlying molecular mechanisms that influence the fibroblast-derived exosomes on the electrical remodeling of cardiomyocytes are blurry. Therefore, our objective is to study the regulation of cardiac electrophysiology by exosomes linked to KCa3.1. Methods: Atrial myocytes (AMs) and atrial fibroblasts collected from Sprague-Dawley suckling rats were isolated and cultured individually. The cellular atrial fibrillation (AF) model was then established via electrical stimulation (1.0 v/cm, 10 Hz), and fibroblast-derived exosomes were isolated via ultracentrifugation. Moreover, these exosomes were co-cultured with AMs to investigate their influences on KCa3.1 and its potential mechanism. Various techniques, such as nanoparticle tracking analysis, transmission electron microscopy, whole-cell patch clamp technique, reverse-transcription polymerase chain reaction (RT-PCR), Western blot, and immunofluorescence, were used. Results: Rapid pacing promoted the secretion of exosomes from atrial fibroblasts ( P < 0.05), along with elevating the miR-21-5p expression level in atrial fibroblasts and exosomes ( P < 0.01). The expression of protein and current density of the KCa3.1 channel significantly increased after rapid pacing in AMs (0.190 ± 0.010 vs. 0.513 ± 0.057, P < 0.001). The KCa3.1 channel expression and PI3K/AKT pathway were further amplified after co-culturing of AMs with exosomes secreted by atrial fibroblasts (0.513 ± 0.057 vs. 0.790 ± 0.020, P < 0.001). However, the KCa3.1 expression was reversed after the cells were co-cultured with exosomes secreted by atrial fibroblasts transfected with miR-21-5p inhibitors (0.790 ± 0.020 vs. 0.570 ± 0.056, P < 0.001) or after the use of LY294002, a PI3K/AKT pathway inhibitor (0.676 ± 0.025 vs. 0.480 ± 0.043, P < 0.001). Conclusions: Rapid pacing promoted the secretion of exosomes from fibroblasts, and the miR-21-5p was upmodulated in exosomes. Moreover, the miR-21-5p enriched in exosomes up-regulated the KCa3.1 channel expression in AMs via the PI3K/AKT pathway.
No need to treat atrial fibrillation. An unexpected perspective.
Marco Moscarelli
Khalil Fattouch

Marco Moscarelli

and 1 more

September 01, 2022
Heart failure and atrial fibrillation are often associated. Both conditions share pathophysiology and risk factor; as an example, atrial fibrillation may be regarded as either the ‘cause’ or the ‘consequence’ of heart failure. If coexistent, they are associated to very poor outcome. With this in mind, finding effective therapy for patients presenting with both heart failure and atrial fibrillation remains of paramount importance. There are also little evidence of the role and benefit of surgical atrial fibrillation ablation concomitant to heart surgery (i.e., coronary or valve surgery).
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