bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical kinetics and promoted Co-immobilization for efficient catalytic carbonylation of ethylene oxide into methyl 3-hydroxypropionate
Authors: Luo Jingjie , Liu Pengcheng , Yang Wenhao , Niu Hongyu , Li Shaojie , Liang Changhai
Published: July 2022

The carbonylative transformation of ethylene oxide (EO) into methyl 3-hydroxypropionate (3-HPM) is a key process for the production of 1,3-propanediol (1,3-PDO), which is currently viewed as one of the most promising monomers and intermediates in polyester and pharmaceuticals industry. In this work, a homogeneous reaction system using commercial Co2(CO)8 was first studied for the carbonylation of EO to 3-HPM. The catalytic behavior was related to the electronic environment of N on aromatic rings of ligands, where N with rich electron density induced a stronger coordination with Co center and higher EO transformation. A reaction order of 2.1 with respect to EO and 0.3 with respect to CO was unraveled based on the kinetics study. The 3-HPM yield reached 91.2% at only 40°C by Co2(CO)8 coordinated with 3-hydroxypyridine. However, Co-containing colloid was formed during the reaction, causing the tough separation and impossible recycling of samples. Concerning the sustainable utilization, Co particles immobilized on pre-treated carbon nanotubes (Co/CNT-C) were designed via an in situ reduced colloid method. It is remarkable that unlike conventional Co/CNT, Co/CNT-C was highly selective toward the transformation of EO to 3-HPM with a specific rate of 52.2 mmol·gCo-1·h-1, displaying a similar atomic efficiency to that of coordinated Co2(CO)8. After reaction, the supported Co/CNT-C catalyst could be easily separated from the liquid reaction mixture, leading to a convenient cyclic utilization.
Melatonin Enhances the Postharvest Disease Resistance of Blueberries Fruit by Modulating the Jasmonic Acid Signaling Pathway and Phenylpropanoid Metabolites
Authors: Qu Guangfan , Wu Wenneng , Ba Liangjie , Ma Chao , Ji Ning , Cao Sen
Published: July 2022

In this study, to investigate the physiological and molecular mechanisms of melatonin inhibiting the postharvest rot of blueberry fruits, blueberry fruits were dipped in 0.3 mmol L−1 melatonin solution for 3 min and stored at 0°C for 80 days. The results indicated that melatonin did not significantly (p > 0.05) inhibit the mycelial growth or spore germination of Alternaria alternata, Botrytis cinerea, and Colletotrichum gloeosporioides. In addition, an in vivo study revealed that melatonin treatment increased the enzymatic activities of phenylalanine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), 4-coumarate-CoA ligase (4CL), cinnamyl alcohol dehydrogenase (CAD), polyphenol oxidase (PPO), and peroxidase (POD) in fruits. Furthermore, genes related to jasmonic acid synthesis were upregulated (VaLOX, VaAOS, and VaAOC), as were those related to pathogenesis-related proteins (VaGLU and VaCHT) and phenylpropane metabolism (VaPAL, VaC4H, Va4CL, VaCAD, VaPPO, and VaPOD), which promoted the accumulation of total phenols, flavonoids, anthocyanins, and lignin in the fruits. These results suggest that melatonin enhances the postharvest disease resistance of blueberry fruits by mediating the jasmonic acid signaling pathway and the phenylpropane pathway.
MicroRNA-29b/graphene oxide–polyethyleneglycol–polyethylenimine complex incorporated within chitosan hydrogel promotes osteogenesis
Authors: Qin Han , Ji Yujie , Li Guangyue , Xu Xiaohui , Zhang Chuangwei , Zhong Wenjie , Xu Shihan , Yin Yuanyuan , Song Jinlin
Published: July 2022

MicroRNAs (miRNAs) play a pivotal role in regulating a number of physiologic and pathologic processes including bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation, making them a candidate used to promote osteogenesis. However, due to intrinsic structure and characteristics, “naked” miRNAs are unstable in serum and could not pass across the cellular membrane. Nano delivery systems seem to be a solution to these issues. Recently, graphene oxide (GO)-based nanomaterials are considered to be promising for gene delivery due to their unique physiochemical characteristics such as high surface area, biocompatibility, and easy modification. In this work, a GO-based nanocomplex functionalized by polyethyleneglycol (PEG) and polyethylenimine (PEI) was prepared for loading and delivering miR-29b, which participates in multiple steps of bone formation. The nanocomplex revealed good biocompatibility, miRNA loading capacity, and transfection efficiency. The miR-29b/GO-PEG-PEI nanocomplex was capsulated into chitosan (CS) hydrogel for osteogenesis. In vitro and in vivo evaluation indicated that miR-29b/GO-PEG-PEI@CS composite hydrogel was able to promote BMSC osteogenic differentiation and bone regeneration. All these results indicate that PEG/PEI functionalized GO could serve as a promising candidate for miRNA cellular delivery, and the miR-29b/GO-PEG-PEI@CS hydrogel has the potential for repairing bone defects in vivo.
A novel and highly efficient Zr-containing catalyst supported by biomass-derived sodium carboxymethyl cellulose for hydrogenation of furfural
Authors: Hao Jianxiu , Zhang Yafang , Zhang Tianyuan , Zhou Huacong , Liu Quansheng , Zhi Keduan , Li Na , He Runxia
Published: July 2022

Functional use of biomass based on its structural properties is an efficient approach for the valuable utilization of biomass resources. In this work, carboxymethyl cellulose zirconium-based catalyst (Zr-CMC) was constructed by the coordination between the carboxylic groups in sodium carboxymethyl cellulose (CMC-Na) with transition metal Zr4+. The prepared catalyst was applied into the synthesis of furfuryl alcohol (FAL) by catalytic transfer hydrogenation of biomass-derived furfural (FF) using isopropanol as hydrogen donor. Both the preparation conditions and the reaction conditions of Zr-CMC catalyst were investigated and optimized. The results showed that Zr-CMC was efficient for the reaction with the FF conversion, FAL yield and selectivity reaching to 92.5%, 91.5 %, and 99.0%, respectively, under the mild conditions (90°C). Meanwhile, the Zr-CMC catalyst could be reused at least for five times without obvious decrease in efficiency, indicating the catalyst had excellent stability. With the advantages of sustainable raw materials, high efficiency, and excellent stability, the prepared catalyst is potential for application in the field of biomass conversion.
Imaging Techniques: Essential Tools for the Study of SARS-CoV-2 Infection
Authors: Deroubaix Aurélie , Kramvis Anna
Published: July 2022

The world has seen the emergence of a new virus in 2019, SARS-CoV-2, causing the COVID-19 pandemic and millions of deaths worldwide. Microscopy can be much more informative than conventional detection methods such as RT-PCR. This review aims to present the up-to-date microscopy observations in patients, the in vitro studies of the virus and viral proteins and their interaction with their host, discuss the microscopy techniques for detection and study of SARS-CoV-2, and summarize the reagents used for SARS-CoV-2 detection. From basic fluorescence microscopy to high resolution techniques and combined technologies, this article shows the power and the potential of microscopy techniques, especially in the field of virology.
Redox Imbalance and Its Metabolic Consequences in Tick-Borne Diseases
Authors: Groth Monika , Skrzydlewska Elżbieta , Dobrzyńska Marta , Pancewicz Sławomir , Moniuszko-Malinowska Anna
Published: July 2022

One of the growing global health problems are vector-borne diseases, including tick-borne diseases. The most common tick-borne diseases include Lyme disease, tick-borne encephalitis, human granulocytic anaplasmosis, and babesiosis. Taking into account the metabolic effects in the patient’s body, tick-borne diseases are a significant problem from an epidemiological and clinical point of view. Inflammation and oxidative stress are key elements in the pathogenesis of infectious diseases, including tick-borne diseases. In consequence, this leads to oxidative modifications of the structure and function of phospholipids and proteins and results in qualitative and quantitative changes at the level of lipid mediators arising in both reactive oxygen species (ROS) and ROS enzyme–dependent reactions. These types of metabolic modifications affect the functioning of the cells and the host organism. Therefore, links between the severity of the disease state and redox imbalance and the level of phospholipid metabolites are being searched, hoping to find unambiguous diagnostic biomarkers. Assessment of molecular effects of oxidative stress may also enable the monitoring of the disease process and treatment efficacy.
Heterologous production of the adhesin LIC13411 from pathogenic Leptospira facilitates binding of non-pathogenic Leptospira in vitro and in vivo
Authors: Surdel Matthew C. , Hahn Beth L. , Anderson Phillip N. , Coburn Jenifer
Published: July 2022

Leptospirosis is an important cause of morbidity and mortality worldwide. Disease severity ranges from asymptomatic colonization to widespread hemorrhage and multiorgan dysfunction. The causative agents, Leptospira spp., are zoonotic Gram-negative spirochetes. One important step in pathogenesis is binding of bacterial adhesins to host components. Previously our laboratory identified two L. interrogans candidate adhesins, LIC11574 and LIC13411, that bind to VE-cadherin in vitro. In the current study, we demonstrate the ability of two strains of pathogenic L. interrogans to disrupt the localization of VE-cadherin, a protein important to maintaining inter-endothelial junctions. Purified MBP-LIC11574 and MBP-LIC13411 bind human dermal microvascular endothelial cells in a pattern reminiscent of VE-cadherin, but do not disrupt VE-cadherin localization. Genes encoding the candidate adhesins from pathogenic Leptospira were cloned in an overexpression vector and introduced into non-pathogenic L. biflexa, creating gain-of-function strains producing LIC11574 or LIC13411. Protein production and localization to the outer membrane were confirmed by Triton X-114 fractionation. Although these strains do not disrupt VE-cadherin localization, production of LIC13411 increases binding of non-pathogenic Leptospira to human endothelial cells and specifically to VE-cadherin. In a short-term murine model of infection, LIC13411 production led to increased burdens of the non-pathogen in the lung, liver, kidney, and bladder. These data confirm the role of LIC13411 as an adhesin in Leptospira spp. and implicate it in dissemination to multiple organs. Importantly, anti-adhesin therapy has been shown to have many benefits over classical antibiotics. Taken together, this work provides novel insight into the pathogenesis of Leptospira spp. and identifies LIC13411 as a potential prophylactic and therapeutic target.
Identification of Prognostic Metabolomic Biomarkers at the Interface of Mortality and Morbidity in Pre-Existing TB Cases Infected With SARS-CoV-2
Authors: Diboun Ilhame , Cyprian Farhan S. , Anwardeen Najeha Rizwana , Yassine Hadi M. , Elrayess Mohamed A. , Rahmoon Samreen Mumtaz , Sayed Sarah Khaled , Schuchardt Sven , Khatib Malkan , Bansal Devendra , Farag Elmoubashar Abu Baker Abd , Emara Mohamed M. , Abdallah Abdallah M.
Published: July 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection currently remains one of the biggest global challenges that can lead to acute respiratory distress syndrome (CARDS) in severe cases. In line with this, prior pulmonary tuberculosis (TB) is a risk factor for long-term respiratory impairment. Post-TB lung dysfunction often goes unrecognized, despite its relatively high prevalence and its association with reduced quality of life. In this study, we used a metabolomics analysis to identify potential biomarkers that aid in the prognosis of COVID-19 morbidity and mortality in post-TB infected patients. This analysis involved blood samples from 155 SARS-CoV-2 infected adults, of which 23 had a previous diagnosis of TB (post-TB), while 132 did not have a prior or current TB infection. Our analysis indicated that the vast majority (~92%) of post-TB individuals showed severe SARS-CoV-2 infection, required intensive oxygen support with a significantly high mortality rate (52.2%). Amongst individuals with severe COVID-19 symptoms, we report a significant decline in the levels of amino acids, notably the branched chains amino acids (BCAAs), more so in the post-TB cohort (FDR <= 0.05) in comparison to mild and asymptomatic cases. Indeed, we identified betaine and BCAAs as potential prognostic metabolic biomarkers of severity and mortality, respectively, in COVID-19 patients who have been exposed to TB. Moreover, we identified serum alanine as an important metabolite at the interface of severity and mortality. Hence, our data associated COVID-19 mortality and morbidity with a long-term metabolically driven consequence of TB infection. In summary, our study provides evidence for a higher mortality rate among COVID-19 infection patients who have history of prior TB infection diagnosis, which mandates validation in larger population cohorts.
Host and Species-Specificities of Pattern Recognition Receptors Upon Infection With Leptospira interrogans
Authors: Bonhomme Delphine , Werts Catherine
Published: July 2022

Leptospirosis is a zoonotic infectious disease affecting all vertebrates. It is caused by species of the genusLeptospira, among which are the highly pathogenicL. interrogans. Different mammals can be either resistant or susceptible to the disease which can present a large variety of symptoms. Humans are mostly asymptomatic after infection but can have in some cases symptoms varying from a flu-like syndrome to more severe forms such as Weil’s disease, potentially leading to multiorgan failure and death. Similarly, cattle, pigs, and horses can suffer from acute forms of the disease, including morbidity, abortion, and uveitis. On the other hand, mice and rats are resistant to leptospirosis despite chronical colonization of the kidneys, excreting leptospires in urine and contributing to the transmission of the bacteria. To this date, the immune mechanisms that determine the severity of the infection and that confer susceptibility to leptospirosis remain enigmatic. To our interest, differential immune sensing of leptospires through the activation of or escape from pattern recognition receptors (PRRs) by microbe-associated molecular patterns (MAMPs) has recently been described. In this review, we will summarize these findings that suggest that in various hosts, leptospires differentially escape recognition by some Toll-like and NOD-like receptors, including TLR4, TLR5, and NOD1, although TLR2 and NLRP3 responses are conserved independently of the host. Overall, we hypothesize that these innate immune mechanisms could play a role in determining host susceptibility to leptospirosis and suggest a central, yet complex, role for TLR4.
Sensitive and visual identification of Chlamydia trachomatis using multiple cross displacement amplification integrated with a gold nanoparticle-based lateral flow biosensor for point-of-care use
Authors: Chen Xu , Yuan Wei , Zhou Qingxue , Tan Yan , Wang Ronghua , Dong Shilei
Published: July 2022

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infection (STI) and remains a major public health challenge, especially in less-developed regions. Establishing a rapid, inexpensive, and easy-to-interpret point-of-care (POC) testing system for C. trachomatis could be critical for its treatment and limiting further transmission. Here, we devised a novel approach termed a multiple cross displacement amplification integrated with gold nanoparticle-based lateral flow biosensor (MCDA-AuNPs-LFB) for the highly specific, sensitive, user-friendly, and rapid identification of C. trachomatis in clinical samples. A suite of MCDA primers based on the C. trachomatis ompA gene from 14 serological variants (serovar A-K, L1, L2, and L3) were successfully designed and used to establish the assay. Optimal assay conditions were identified at 67°C, and the detection procedure, including nucleic acid preparation (approximately 5 min), MCDA amplification (30 min), and AuNPs-LFB visual readout (within 2 min), was completed within 40 min. The all-in cost for each test was approximately $5.5 USD. The limit of detection (LoD) was 10 copies/reaction, and no cross-reaction was observed with non-C. trachomatis microbes. A total of 135 suspected C. trachomatis-infection genital secretion samples were collected and simultaneously detected using real-time quantitative PCR (qPCR) in our assay. Compared with the qPCR technology, the MCDA-AuNPs-LFB sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 96.20%, 94.92%, and 100%, respectively. Hence, our MCDA-AuNP-LFB assay exhibited considerable potential for POC testing and could be used to identify C. trachomatis in clinical settings, particularly in low-income regions.
Four Methodological Guidelines to Evaluate the Research Impact of Co-produced Climate Services
Authors: Englund Mathilda , André Karin , Gerger Swartling Åsa , Iao-Jörgensen Jenny
Published: July 2022

As climate change impacts unfold across the globe, growing attention is paid toward producing climate services that support adaptation decision-making. Academia, funding agencies, and decision-makers generally agree that stakeholder engagement in co-producing knowledge is key to ensure effective decision support. However, co-production processes remain challenging to evaluate, given their many intangible effects, long time horizons, and inherent complexity. Moreover, how such evaluation should look like is understudied. In this paper, we therefore propose four methodological guidelines designed to evaluate co-produced climate services: (i) engaging in adaptive learning by applying developmental evaluation practices, (ii) building and refining a theory of change, (iii) involving stakeholders using participatory evaluation methods, and (iv) combining different data collection methods that incorporate visual products. These methodological guidelines offset previously identified evaluation challenges and shortcomings, and can be used to help stakeholders rethink research impact evaluation through their complementary properties to identify complex change pathways, external factors, intangible effects, and unexpected outcomes.
Enhanced weathering potentials—the role of in situ CO2 and grain size distribution
Authors: Amann Thorben , Hartmann Jens , Hellmann Roland , Pedrosa Elisabete Trindade , Malik Aman
Published: July 2022

The application of rock powder on agricultural land to ameliorate soils and remove carbon dioxide (CO2) from the air by chemical weathering is still subject to many uncertainties. To elucidate the effects of grain size distribution and soil partial pressure of carbon dioxide (pCO2) levels on CO2 uptake rates, two simple column experiments were designed and filled nearly daily with an amount of water that simulates humid tropical conditions, which prevail in areas known for being hotspots of weathering. Multiple materials (dunite, basanite, agricultural oxisol, a combination of the latter two, and loess) were compared under ambient and 100% CO2 atmosphere. In a second series, single material columns (dunite) were filled with three different grain size distributions. Total alkalinity, pH, major ions, and dissolved silica were determined in the outflow water of the columns for about 300 days. Under ambient atmospheric conditions, the CO2 consumption was the lowest in the oxisol column, with 100 t CO2 km−2 year−1, while dunite and basanite showed similar consumption rates (around 220 t CO2 km−2 year−1). The values are comparable to high literature values for ultramafic lithologies. Interestingly, the mixture of basanite and oxisol has a much higher consumption rate (around 430 t CO2 km−2 year−1) than the basanite alone. The weathering fluxes under saturated CO2 conditions are about four times higher in all columns, except the dunite column, where fluxes are increased by a factor of more than eleven. Grain size distribution differences also play a role, with the highest grain surface area normalized weathering rates observed in the columns with coarser grains, which at first seems counterintuitive. Our findings point to some important issues to be considered in future experiments and a potential rollout of EW as a carbon dioxide removal method. Only in theory do small grain sizes of the spread-material yield higher CO2 drawdown potentials than coarser material. The hydrologic conditions, which determine the residence times in the pore space, i.e., the time available for weathering reactions, can be more important than small grain size. Saturated-CO2 column results provide an upper limit for weathering rates under elevated CO2.
Embodied Cognition, Kinaesthetic Knowledge, and Kinesic Imagination in Literature and Visual Arts
Authors: Bolens Guillemette
Published: July 2022

Embodied cognition, kinaesthetic knowledge, and kinesic imagination are central not only to acts of creation but also to the reception of artworks. This article substantiates this claim by focusing on sensorimotricity in art and literature, presenting two sets of analytical distinctions that pertain to dynamics in gesture and movement. The first set of distinctions—kinesis, kinaesthesia, kinetics, and kinematics—and the second set—timing, tempo, and momentum—are used to analyse literary descriptions and visual depictions of movements. The first set of distinctions is discussed in the first part of the article in relation to medieval drawings and literary excerpts from different historical periods (in works by Ovid, Shakespeare, and Proust). The second part focuses on visual arts and leads to an analysis of Bruegel'sFall of the Rebel Angels, while the third part presents a kinesic analysis of the Apollo and Daphne episode in Ovid'sMetamorphoses. A heightened attention to the cognitive processing of kinesic features in acts of reception enhances the role and responsibility of readers and viewers in the ways in which they grasp the movement-based meanings formalized by artists of various cultures and historical periods.
An expanding cityscape and its multi-scale effects on lizard distribution
Authors: Thaker Maria , Amdekar Madhura S. , Mohanty Nitya P. , Nageshkumar Abhijit K. , Prakash Harish , Seshadri K. S
Published: July 2022

Urbanization results in complex and variable changes to environmental conditions, which translate to shifts in selection pressures for organisms. Size of a city as well as the intensity and extent of urbanization can synergistically influence how organisms are impacted. However, less is known about how landscape heterogeneity, rate of land-use change, and scale of urbanization affect species persistence. We evaluate the ways in which urbanization changes the environment and examine how some of these environmental factors influence the presence of the lizard Psammophilus dorsalis (Peninsular rock agama), in Bengaluru, India. Variability in environmental factors across the study area was characterised by measures of habitat composition and diversity, habitat connectivity, rate of habitat change, predation pressure, land surface temperature (LST) and artificial light at night (ALAN), that were derived from remotely sensed and citizen science data. Most of these factors showed high variance across two measures of urbanization: distance from city center and proportion of built-up area. Habitat diversity and ALAN were the only two factors that changed predictably and in a non-linear way, with distance from the city center and proportion of built-up area. We then used a multi-scale approach to examine the relative importance of some these environmental factors at the landscape scale, as well as additional factors at the microhabitat-scale, in predicting the presence and relative abundance of P. dorsalis respectively. At the landscape scale, LST, which is positively correlated with proportion of cropland, predicted lizard presence; whereas at the microhabitat scale, P. dorsalis was more likely to be found in sites with higher proportions of rocks. Overall, we demonstrate that urbanization can result in environmental predictors that do not vary linearly across the urbanization gradient. For the iconic rock agama, many of these environmental factors do not seem to be strong selection pressures that influence their distribution in the expanding cityscape. Whether this urban utilizer can continue to persist with increasing anthropogenic development is uncertain. To better understand drivers of species persistence, we emphasize the importance of quantifying urbanization across multiple axes, considering environmental factors that are relevant to species at different spatial and temporal scales.
Four-dimensional flow cardiac magnetic resonance assessment of left ventricular diastolic function
Authors: Ashkir Zakariye , Myerson Saul , Neubauer Stefan , Carlhäll Carl-Johan , Ebbers Tino , Raman Betty
Published: July 2022

Left ventricular diastolic dysfunction is a major cause of heart failure and carries a poor prognosis. Assessment of left ventricular diastolic function however remains challenging for both echocardiography and conventional phase contrast cardiac magnetic resonance. Amongst other limitations, both are restricted to measuring velocity in a single direction or plane, thereby compromising their ability to capture complex diastolic hemodynamics in health and disease. Time-resolved three-dimensional phase contrast cardiac magnetic resonance imaging with three-directional velocity encoding known as ‘4D flow CMR’ is an emerging technology which allows retrospective measurement of velocity and by extension flow at any point in the acquired 3D data volume. With 4D flow CMR, complex aspects of blood flow and ventricular function can be studied throughout the cardiac cycle. 4D flow CMR can facilitate the visualization of functional blood flow components and flow vortices as well as the quantification of novel hemodynamic and functional parameters such as kinetic energy, relative pressure, energy loss and vorticity. In this review, we examine key concepts and novel markers of diastolic function obtained by flow pattern analysis using 4D flow CMR. We consolidate the existing evidence base to highlight the strengths and limitations of 4D flow CMR techniques in the surveillance and diagnosis of left ventricular diastolic dysfunction.
Predictors of restenosis following percutaneous coronary stent implantation: The role of trimetazidine therapy
Authors: Csató Gábor , Erdei Nóra , Ványai Beatrix , Balla Tímea , Czuriga Dániel , Csanádi Zoltán , Koszegi Zsolt , Édes István , Szabó Gábor Tamás
Published: July 2022

Aims

In-stent restenosis (ISR) is an unresolved problem following percutaneous coronary intervention (PCI), having a negative impact on clinical outcome. The main goal of this study was to find new independent predictors that may influence the development of ISR.

Methods and results

In this retrospective analysis, 653 PCI patients were involved. All patients had coronary stent implantation and a follow-up coronary angiography. Based on the presence of ISR at follow-up, patients were divided into two groups: 221 in the ISR and 432 in the control group. When evaluating the medical therapy of patients, significantly more patients were on trimetazidine (TMZ) in the control compared to the ISR group (p = 0.039). TMZ was found to be an independent predictor of a lower degree of ISR development (p = 0.007). TMZ treatment was especially effective in bare metal stent (BMS)-implanted chronic coronary syndrome (CCS) patients with narrow coronary arteries. The inflammation marker neutrophil to lymphocyte ratio (NLR) was significantly elevated at baseline in the ISR group compared to controls. The reduction of post-PCI NLR was associated with improved efficacy of TMZ to prevent ISR development. Drug eluting stent implantation (p < 0.001) and increased stent diameter (p < 0.001) were the most important independent predictors of a lower degree of ISR development, while the use of longer stents (p = 0.005) was a major independent predictor of an increased ISR risk.

Conclusion

TMZ reduces the occurrence of ISR following PCI, with special effectiveness in BMS-implanted patients having CCS and narrow coronary arteries. TMZ treatment may help to lower ISR formation in countries with high BMS utilization rates.
Prophylactic exercise-derived circulating exosomal miR-125a-5p promotes endogenous revascularization after hindlimb ischemia by targeting endothelin converting enzyme 1
Authors: Qiu Xueting , Zhou Jipeng , Xu Yanying , Liao Longsheng , Yang Huijun , Xiang Yuan , Zhou Zhengshi , Sun Quan , Chen Minghong , Zhang Jiaxiong , Wu Wanzhou , Zhu Lingping , You Baiyang , He Lingfang , Luo Ying , Li Zhenyu , Li Chuanchang , Bai Yongping
Published: July 2022

Background

Prophylactic exercise improves clinical outcomes in patients experiencing severe ischemic diseases. Previous studies have shown that exercise could alter the amount or content of circulating exosomes. However, little is known about the role of precursory exercise-derived circulating exosomes (Exe-Exo) in ischemic diseases. We therefore aimed to explore the function and mechanism of Exe-Exo in endogenous revascularization and perfusion recovery in peripheral arterial disease.

Methods and Results

We first determined that 4 weeks of precursory treadmill exercise improved perfusion recovery on days 7, 14 and 21 after unilateral femoral artery ligation (FAL) but had no effect immediately after ligation. Then, local muscle delivery of Exe-Exo promotes arteriogenesis, angiogenesis and perfusion recovery, which could be abolished by GW4869, a well-recognized pharmacological agent inhibiting exosome release. This suggests that Exe-Exo mediated exercise-induced revascularization. In vitro, Exe-Exo enhanced endothelial cell proliferation, migration and tube formation. In addition, we identified miR-125a-5p as a novel exerkine through exosomal miRNA sequencing and RT-qPCR validation. Inhibition of miR-125a-5p abrogated the beneficial effects of Exe-Exo both in vivo and in vitro. Mechanistically, these exercise-afforded benefits were attributed to the exosomal miR-125a-5p downregulation of ECE1 expression and the subsequent activation of the AKT/eNOS downstream signaling pathway. Specifically, skeletal muscle may be a major tissue source of exercise-induced exosomal miR-125a-5p via fluorescence in situ hybridization.

Conclusions

Endogenous circulating exosomal miR-125a-5p promotes exercise-induced revascularization via targeting ECE1 and activating AKT/eNOS downstream signaling pathway. Identify exosomal miR-125a-5p as a novel exerkine, and highlight its potential therapeutic role in the prevention and treatment of peripheral arterial disease.
Plasma fingerprint of free fatty acids and their correlations with the traditional cardiac biomarkers in patients with type 2 diabetes complicated by coronary heart disease
Authors: Hu Ting , Zhang Wen , Han Feifei , Zhao Rui , Liu Lihong , An Zhuoling
Published: July 2022

Type 2 diabetes mellitus (T2DM) is a well-established risk factor for cardiovascular disease, with at least 2–3 fold higher risk of cardiovascular diseases than non-diabetics. Free fatty acids (FFAs) are believed to play important roles in the occurrence of cardiovascular disease in people with T2DM. The aim of this study was to investigate the fingerprint of plasma FFAs and their correlations with the tradition risk factors of cardiovascular disease in T2DM patients complicated by coronary heart disease (CHD-T2DM). A total of 401 participants, including healthy control (HC, n = 143), T2DM patients (n = 134), and CHD-T2DM patients (n = 126) were enrolled in this study. Plasma levels of 36 FFAs with carbon chain length ranged from 3 to 22 were quantified by using reverse phase ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Tradition risk factors of cardiovascular disease were tested in clinical laboratory, including homocysteine (HCY), creatine kinase (CK), high sensitivity C reactive protein (hsCRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) and so on. Almost all the FFAs with different carbon chain length and unsaturation were significantly upregulated in the T2DM-CHD groups, compared to the HC and T2DM groups. Both n-3 and n-6 polyunsaturated fatty acids (PUFA) were also found to be significantly upregulated in T2DM-CHD group compared to the T2DM group. However, no significantly differences of the n-6/n-3 PUFA ratio, arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio, and arachidonic acid/docosahexaenoic acid (AA/DHA) ratio were observed between T2DM-CHD and T2DM groups. Plasma FFA levels were found to be positively correlated with HCY, CK, hsCRP, NT-proBNP and other tradition risk factors of CHD. Multivariate logistic regression analysis indicated that a dozens of FFAs were the independent risk factors of CHD after adjustment for confounding factors and other risk factors. Excessively high plasma levels of FFAs were demonstrated to be independent risk factors for CHD in patients with T2DM, despite of the differences in chain length, unsaturation, and double bond position.
Successful treatment of fulminant myocarditis with intra-aortic balloon pump counterpulsation combined with immunoglobulin and glucocorticoid in a young male adult
Authors: Li Huanhuan , Li Lun
Published: July 2022

Background

Fulminant myocarditis (FM) is a serious non-specific inflammatory disease of the myocardium. FM tends to occur in adolescents and the course of the disease progresses rapidly. It is prone to cardiogenic shock (CGS) and multiple organ failure (MOF) with high mortality. We report a case of FM with CGS and MOF in a young male who was successfully treated with intra-aortic balloon pump counterpulsation (IABP) combined with intravenous immunoglobulin (IVIG) and glucocorticoid (GC).

Case summary

A 21-year-old previously healthy man presented with fever, headache, and chest tightness. He came to the hospital for emergency treatment. The laboratory data showed that the levels of serum cardiac troponin I (cTnI), N-terminal B-type natriuretic peptide (NT-proBNP), myocardial zymogram, and neutrophils increased. Echocardiography showed pericardial effusion and decreased left ventricular systolic function. ECG showed diffuse ST-segment elevation. He was clinically diagnosed with FM and admitted to the intensive care unit for treatment. Within 48 h of admission, the clinical course of the patient deteriorated rapidly, with CGS accompanied by MOF, high atrioventricular block (AVB), and ventricular tachycardia (VT). After using mechanical circulatory support (MCS) therapy with IABP, IVIG, GC, continuous renal replacement therapy (CRRT), and mechanical ventilation complicated with a temporary cardiac pacemaker, he recovered normal cardiac function. He made a full recovery and was discharged home on day 21.

Discussion

For patients with FM, early diagnosis, close monitoring, timely use of MCS devices, and active comprehensive treatment are very important. MCS devices such as IABP can become lifesaving tools for the treatment of FM.
Physical performance and glycemic control under SGLT-2-inhibitors in patients with type 2 diabetes and established atherosclerotic cardiovascular diseases or high cardiovascular risk (PUSH): Design of a 4-week prospective observational study
Authors: Frundi Devine S. , Kettig Eva , Popp Lena Luise , Hoffman Melanie , Dumartin Marine , Hughes Magali , Lamy Edgar , Fru Yvonne Joko Walburga , Bano Arjola , Muka Taulant , Wilhelm Matthias
Published: July 2022

Background

Type 2 diabetes (T2D) is associated with limitation in physical performance. Results from animal studies report enhancement of physical performance in T2D rodents treated with sodium glucose cotransporter 2 inhibitors (SGLT2is). However, in human patients with T2D and established atherosclerotic cardiovascular disease (ASCVD) or high cardiovascular risk, the impact of guideline directed SGLT2i medication on physical performance has not been sufficiently examined.

Objectives

The main objectives of this study are thus firstly, to assess the changes in physical performance after 4 weeks of exercise therapy in patients with established ASCVD or high cardiovascular risk categorized into three groups according to their glycemic control at baseline. Secondly, to investigate the association of glycemic control at baseline and new guideline directed antidiabetic treatment (inadequate glycemic control and diabetes + new SGLT2i vs. adequate glycemic control and diabetes vs. no diabetes) with change in physical performance.

Methods and design

This is a 4-week prospective observational study of 450 participants with established ASCVD or high cardiovascular risk with or without T2D and without previous SGLT2i medication undergoing exercise therapy during inpatient rehabilitation in a single center in Switzerland. Upon admission, participants are categorized into 3 groups of 150 participants each according to their glycemic control. Group I consisting of participants with inadequately controlled T2D defined as mean fasting plasma glucose (FPG) of ≥7 mmol/L, who are consequently administered new treatment with an SGLT2i. Group II comprises of participants with adequately controlled T2D with mean FPG of <7 mmol/L requiring no antidiabetic medication change. Group III consists of participants with no diabetes and mean FPG of ≤ 5.5 mmol/L. Primary outcomes are 6-min walk distance and rate of perceived exertion. Secondary outcomes are echocardiographic parameters (left ventricular mass index; global longitudinal strain average; end-diastolic volume), fatigue, muscle, metabolic, and anthropometric measures.

Ethics and dissemination

This study is conducted in accordance with the Declaration of Helsinki with ethical approval from the Cantonal Ethical Commission of Bern, Switzerland. The results will be published in a peer-reviewed journal. The implementation and reporting will be according to the SPIRIT guidelines.

Study protocol registration

https://www.clinicaltrials.gov/, identifier: NCT03422263.
In vitro benchtop mock circulatory loop for heart failure with preserved ejection fraction emulation
Authors: Malone Andrew , Gallagher Sean , Saidi Jemil , Rizq Gina , O’Dowd Enda , Vallence Derek , Hameed Aamir
Published: July 2022

In this work, a novel mock circulatory loop (MCL) is presented that is capable of simulating both healthy cardiac function and Heart Failure with preserved Ejection Fraction (HFpEF). This MCL differs from others presented in the literature as it features two independently actuated heart chambers, representing the left atrium and the left ventricle. This is an important improvement over other designs as it allows for potential HFpEF treatments to be examined, not just in relation to their effect on the left ventricle but also on the left atrium. The aim of this work was to show that novel MCL designs could be developed to allow for testing of new mechanical circulatory support devices for the treatment of HFpEF. Two loop configurations are presented, one featuring hard PVC cylindrical chambers and one that features soft silicone chambers which are anatomically analogous to the native heart. We show that both MCLs are capable of simulating the onset of HFpEF with a sustained increase in diastolic pressure of 62.03% and a sustained decrease in end diastolic volume (EDV) of 14.24%.
Research progress on the predictive value of electrocardiographic indicators in the diagnosis and prognosis of children with vasovagal syncope
Authors: Zhao Ting , Wang Shuo , Wang Miao , Cai Hong , Wang Yuwen , Xu Yi , Zou Runmei , Wang Cheng
Published: July 2022

Neurally mediated syncope (NMS) is a common type of syncope in children in clinical practice, among which vasovagal syncope (VVS) is the most frequent. In recent years, more and more studies have been carried out to assess the diagnosis and prognosis of VVS. The electrocardiographic indicators such as heart rate variability (HRV), QT dispersion (QTd), P-wave dispersion (Pd), ventricular late potentials (VLP), deceleration ability of heart rate (DC), etc., are easy to obtain and inexpensive. With the help of electrocardiographic indicators, the diagnostic procedure and individualized treatment strategies of pediatric VVS can be optimized. This article reviews the value of electrocardiographic indicators in the diagnosis and prognosis of children with VVS.
Association between baseline smoking status and clinical outcomes following myocardial infarction
Authors: Oh Seok , Kim Ju Han , Cho Kyung Hoon , Kim Min Chul , Sim Doo Sun , Hong Young Joon , Ahn Youngkeun , Jeong Myung Ho
Published: July 2022

Background

Whether the effect of smoking on clinical outcomes following an acute myocardial infarction (AMI) is beneficial or detrimental remains inconclusive. We invesetigated the effect of smoking on the clinical outcomes in patients following an AMI.

Methods

Among 13,104 patients between November 2011 and June 2015 from a nationwide Korean AMI registry, a total of 10,193 participants were extracted then classified into two groups according to their smoking habit: (1) smoking group (n = 6,261) and (2) non-smoking group (n = 3,932). The participants who smoked were further subclassified according to their smoking intensity quantified by pack years (PYs): (1) <20 PYs (n = 1,695); (2) 20–40 PYs (n = 3,018); and (3) ≥40 PYs (n = 2,048). Each group was compared to each other according to treatment outcomes. The primary outcome was the incidence of major adverse cardiac and cerebrovascular events (MACCEs), which is a composite of all-cause mortality, non-fatal MI (NFMI), any revascularization, cerebrovascular accident, rehospitalization, and stent thrombosis. Secondary outcomes included the individual components of MACCEs. The Cox proportional hazard regression method was used to evaluate associations between baseline smoking and clinical outcomes following an AMI. Two propensity score weighting methods were performed to adjust for confounders, including propensity score matching and inverse probability of treatment weighting.

Results

While the incidence of all clinical outcomes, except for stent thrombosis, was lower in the smoking group than in the non-smoking group in the unadjusted data, the covariates-adjusted data showed statistical attenuation of these differences but a higher all-cause mortality in the smoking group. For smokers, the incidence of MACCEs, all-cause mortality, cardiac and non-cardiac death, and rehospitalization was significantly different between the groups, with the highest rates of MACCE, all-cause mortality, non-cardiac death, and rehospitalization in the group with the highest smoking intensity. These differences were statistically attenuated in the covariates-adjusted data, except for MACCEs, all-cause mortality, and non-cardiac death, which had the highest incidence in the group with ≥40 PYs.

Conclusion

Smoking had no beneficial effect on the clinical outcomes following an AMI. Moreover, for those who smoked, clinical outcomes tended to deteriorate as smoking intensity increased.
Trimethylamine N-oxide and its precursors in relation to blood pressure: A mendelian randomization study
Authors: Wang Han , Luo Qiang , Ding Xunshi , Chen Lifang , Zhang Zheng
Published: July 2022

Objective

Previous studies have demonstrated that trimethylamine N-oxide (TMAO) and its precursors, including choline, betaine, and carnitine, are closely associated with blood pressure (BP) changes. Nevertheless, with the limitation of reverse causality and confounder in observational studies, such a relationship remains unclear. We aimed to assess the causal relationship of TMAO and its precursors with BP by the Mendelian Randomization (MR) approach.

Method

In this study, two-sample MR was used to reveal the causal effect of TMAO and its precursors on BP. Pooled data of TMAO and its precursors was from genome-wide association studies (GWAS) which includes summary data of human metabolome in 2,076 European participants from Framingham Heart Study. Summary-level data for BP was extracted from the International Consortium of Blood Pressure-Genome Wide Association Studies. Inverse variance weighted (IVW), MR Egger regression, Maximum likelihood, Weighted median, and MR pleiotropy residual sum and outlier test (MR-PRESSO) were used in this MR analysis.

Results

A total of 160 independent SNP loci were associated with TMAO and three precursors, including 58 associated with TMAO, 29 associated with choline, 44 associated with betaine, and 29 associated with carnitine, were selected. MR results suggested that a 1 unit increase in TMAO should be associated with a 1SD increase in systolic BP mmHg (beta: 0.039, SE, 0.072, p = 0.020). Additionally, our findings also indicated that a 1 unit increase in carnitine should be associated with a 1SD increase in systolic BP mmHg (beta: 0.055, SE: 0.075, p = 0.039). This result was also confirmed by sensitivity analysis methods such as Maximum likelihood, MR-PRESSO, and Weighted median. No effects of betaine or choline on systolic or diastolic BP were observed in the present study.

Conclusion

Our study provides evidence of a causal relationship of TMAO and its precursors with BP, suggesting that mediating the generation of TMAO would be beneficial for lowering BP.
A Rare Ultra-Long-Term Complication of Occluder Recanalization Due to Spontaneous Perforation of Polyvinyl Alcohol Membrane of Atrial Septal Defect Occluder: A Case Report and Review of the Literature
Authors: Xiang Kun , Zhuang Huanwei , Wu Qin , Tang Mi , Yang Jinfu , Fan Chengming
Published: July 2022

Percutaneous closure of atrial septal defect (ASD) has emerged as a feasible alternative strategy to surgical repair in many cardiac centers worldwide. Occluder recanalization due to device failure is a rare and severe complication that often occurs within weeks to years after ASD closure. We reported a rare ultra-long-term complication of occluder recanalization due to delayed spontaneous perforation of polyvinyl alcohol (PVA) membrane of ASD occluder after 18 years of ASD closure. Surgical removal of the faulty device and reconstruction of the atrial septum with a bovine pericardial patch was performed. The patient was discharged and recovered uneventfully without syncope or residual shunt. The cause of this rare complication of spontaneous PVA membrane perforation of the occluder has not been fully detected. To our knowledge, this is the first report about PVA membrane perforation of an occluder that occurred soon after ASD closure.
LMNA mutation leads to cardiac sodium channel dysfunction in the Emery-Dreifuss muscular dystrophy patient
Authors: Perepelina Kseniya , Zaytseva Anastasia , Khudiakov Aleksandr , Neganova Irina , Vasichkina Elena , Malashicheva Anna , Kostareva Anna
Published: July 2022

Pathogenic variants in the LMNA gene are known to cause laminopathies, a broad range of disorders with different clinical phenotypes. LMNA genetic variants lead to tissue-specific pathologies affecting various tissues and organs. Common manifestations of laminopathies include cardiovascular system abnormalities, in particular, cardiomyopathies and conduction disorders. In the present study, we used induced pluripotent stem cells from a patient carrying LMNA p.R249Q genetic variant to create an in vitro cardiac model of laminopathy. Induced pluripotent stem cell-derived cardiomyocytes with LMNA p.R249Q genetic variant showed a decreased sodium current density and an impaired sodium current kinetics alongside with changes in transcription levels of cardiac-specific genes. Thus, we obtained compelling in vitro evidence of an association between LMNA p.R249Q genetic variant and cardiac-related abnormalities.