bluuebunny/crossref_metadata_2025 huggingface dataset:
Circular RNA: Biosynthesis in vitro
Authors: Chen Xinjie , Lu Yuan
Published: December 2021

Circular RNA (circRNA) is a unique type of noncoding RNA molecule. Compared with traditional linear RNA, circRNA is a covalently closed circle produced by a process called backsplicing. CircRNA is abundant in many cells and has rich functions in cells, such as acting as miRNA sponge, protein sponge, protein scaffold, and mRNA regulator. With the continuous development of circRNA study, circRNA has also played an important role in medical applications, including circRNA vaccines and gene therapy. In this review, we illustrate the synthesis of circRNAs in vitro. We focus on biological ligation methods, such as enzymatic ligation from the bacteriophage T4 and ribozyme method. In addition, we summarize the current challenges in the design, synthesis, application, and production of circRNAs, and propose possible solutions in the future. CircRNA is expected to play an essential role in basic research and medical applications.
The Femoral Tunnel Drilling Angle at 45° Coronal and 45° Sagittal Provided the Lowest Peak Stress and Strain on the Bone Tunnels and Anterior Cruciate Ligament Graft
Authors: Cheng Rongshan , Wang Huizhi , Jiang Ziang , Dimitriou Dimitris , Cheng Cheng-Kung , Tsai Tsung-Yuan
Published: December 2021

Purpose: The aims of this study were to 1) investigate the effects of femoral drilling angle in coronal and sagittal planes on the stress and strain distribution around the femoral and tibial tunnel entrance and the stress distribution on the graft, following anterior cruciate ligament reconstruction (ACLR), 2) identify the optimal femoral drilling angle to reduce the risk of the tunnel enlargement and graft failure.

Methods: A validated three-dimensional (3D) finite element model of a healthy right cadaveric knee was used to simulate an anatomic ACLR with the anteromedial (AM) portal technique. Combined loading of 103.0 N anterior tibial load, 7.5 Nm internal rotation moment, and 6.9 Nm valgus moment during normal human walking at joint flexion of 20° was applied to the ACLR knee models using different tunnel angles (30°/45°/60° and 45°/60° in the coronal and sagittal planes, respectively). The distribution of von Mises stress and strain around the tunnel entrances and the graft was calculated and compared among the different finite element ACLR models with varying femoral drilling angles.

Results: With an increasing coronal obliquity drilling angle (30° to 60°), the peak stress and maximum strain on the femoral and tibial tunnel decreased from 30° to 45° and increased from 45° to 60°, respectively. With an increasing sagittal obliquity drilling angle (45° to 60°), the peak stress and the maximum strain on the bone tunnels increased. The lowest peak stress and maximum strain at the ACL tunnels were observed at 45° coronal/45° sagittal drilling angle (7.5 MPa and 7,568.3 μ-strain at the femoral tunnel entrance, and 4.0 MPa and 4,128.7 μ-strain at the tibial tunnel entrance). The lowest peak stress on the ACL graft occurred at 45° coronal/45° sagittal (27.8 MPa) drilling angle.

Conclusions: The femoral tunnel drilling angle could affect both the stress and strain distribution on the femoral tunnel, tibial tunnel, and graft. A femoral tunnel drilling angle of 45° coronal/ 45° sagittal demonstrated the lowest peak stress, maximum strain on the femoral and tibial tunnel entrance, and the lowest peak stress on the ACL graft.
Development and Validation of a Robust Ferroptosis-Related Gene Panel for Breast Cancer Disease-Specific Survival
Authors: Li Pei , Yang Benlong , Xiu Bingqiu , Chi Yayun , Xue Jingyan , Wu Jiong
Published: December 2021

Background: New biomarker combinations have been increasingly developed to improve the precision of current diagnostic and therapeutic modalities. Recently, researchers have found that tumor cells are more vulnerable to ferroptosis. Furthermore, ferroptosis-related genes (FRG) are promising therapeutic targets in breast cancer patients. Therefore, this study aimed to identify FRG that could predict disease-specific survival (DSS) in breast cancer patients.

Methods: Gene expression matrix and clinical data were downloaded from public databases. We included 960, 1,900, and 234 patients from the TCGA, METABRIC, and GSE3494 cohorts, respectively. Data for FRG were downloaded from the FerrDb website. Differential expression of FRG was analyzed by comparing the tumors with adjacent normal tissues. Univariate Cox analysis of DSS was performed to identify prognostic FRG. The TCGA-BRCA cohort was used to generate a nine-gene panel with the LASSO cox regression. The METABRIC and GSE3494 cohorts were used to validate the panel. The panel’s median cut-off value was used to divide the patients into high- or low-risk subgroups. Analyses of immune microenvironment, functional pathways, and clinical correlation were conducted via GO and KEGG analyses to determine the differences between the two subgroups.

Results: The DSS of the low-risk subgroup was longer than that of the high-risk subgroup. The panel’s predictive ability was confirmed by ROC curves (TCGA cohort AUC values were 0.806, 0.695, and 0.669 for 2, 3, and 5 years respectively, and the METABRIC cohort AUC values were 0.706, 0.734, and 0.7, respectively for the same periods). The panel was an independent DSS prognostic indicator in the Cox regression analyses. (TCGA cohort: HR = 3.51, 95% CI = 1.792–6.875, p < 0.001; METABRIC cohort: HR = 1.76, 95% CI = 1.283–2.413, p < 0.001). Immune-related pathways were enriched in the high-risk subgroup. The two subgroups that were stratified by the nine-gene panel were also associated with histology type, tumor grade, TNM stage, and Her2-positive and TNBC subtypes. The patients in the high-risk subgroup, whose CTLA4 and PD-1 statuses were both positive or negative, demonstrated a substantial clinical benefit from combination therapy with anti-CTLA4 and anti-PD-1.

Conclusion: The new gene panel consisting of nine FRG may be used to assess the prognosis and immune status of patients with breast cancer. A precise therapeutic approach can also be possible with risk stratification.
Arhgap21 Deficiency Results in Increase of Osteoblastic Lineage Cells in the Murine Bone Marrow Microenvironment
Authors: Pissarra Mariana Ferreira , Torello Cristiane Okuda , Gomes Rafael Gonçalves Barbosa , Shiraishi Rodrigo Naoto , Santos Irene , Vieira Ferro Karla Priscila , Lopes Matheus Rodrigues , Bergamo Favaro Patricia Maria , Olalla Saad Sara Teresinha , Lazarini Mariana
Published: December 2021

ARHGAP21 is a member of the RhoGAP family of proteins involved in cell growth, differentiation, and adhesion. We have previously shown that the heterozygous Arhgap21 knockout mouse model (Arhgap21+/−) presents several alterations in the hematopoietic compartment, including increased frequency of hematopoietic stem and progenitor cells (HSPC) with impaired adhesion in vitro, increased mobilization to peripheral blood, and decreased engraftment after bone marrow transplantation. Although these HSPC functions strongly depend on their interactions with the components of the bone marrow (BM) niche, the role of ARHGAP21 in the marrow microenvironment has not yet been explored. In this study, we investigated the composition and function of the BM microenvironment in Arhgap21+/− mice. The BM of Arhgap21+/− mice presented a significant increase in the frequency of phenotypic osteoblastic lineage cells, with no differences in the frequencies of multipotent stromal cells or endothelial cells when compared to the BM of wild type mice. Arhgap21+/− BM cells had increased capacity of generating osteogenic colony-forming units (CFU-OB) in vitro and higher levels of osteocalcin were detected in the Arhgap21+/− BM supernatant. Increased expression of Col1a1, Ocn and decreased expression of Trap1 were observed after osteogenic differentiation of Arhgap21+/− BM cells. In addition, Arhgap21+/− mice recipients of normal BM cells showed decreased leucocyte numbers during transplantation recovery. Our data suggest participation of ARHGAP21 in the balanced composition of the BM microenvironment through the regulation of osteogenic differentiation.
CRISPR/Cas9 in Gastrointestinal Malignancies
Authors: Jefremow André , Neurath Markus F. , Waldner Maximilian J.
Published: December 2021

Gastrointestinal (GI) cancers such as colorectal cancer (CRC), gastric cancer (GC), esophageal cancer (EG), pancreatic duct adenocarcinoma (PDAC) or hepatocellular cancer (HCC) belong to the most commonly diagnosed types of cancer and are among the most frequent causes of cancer related death worldwide. Most types of GI cancer develop in a stepwise fashion with the occurrence of various driver mutations during tumor progression. Understanding the precise function of mutations driving GI cancer development has been regarded as a prerequisite for an improved clinical management of GI malignancies. During recent years, CRISPR/Cas9 has developed into a powerful tool for genome editing in cancer research by knocking in and knocking out even multiple genes at the same time. Within this review, we discuss recent applications for CRISPR/Cas9-based genome editing in GI cancer research including CRC, GC, EG, PDAC and HCC. These applications include functional studies of candidate genes in cancer cell lines or organoids in vitro as well as in murine cancer models in vivo, library screening for the identification of previously unknown driver mutations and even gene therapy of GI cancers.
A Functional SNP in the Promoter of LBX1 Is Associated With the Development of Adolescent Idiopathic Scoliosis Through Involvement in the Myogenesis of Paraspinal Muscles
Authors: Xu Leilei , Feng Zhenhua , Dai Zhicheng , Lee Wayne Y. W. , Wu Zhichong , Liu Zhen , Sun Xu , Tang Nelson , Cheng Jack Chun-Yiu , Qiu Yong , Zhu Zezhang
Published: December 2021

Previous studies have shown that LBX1 is associated with adolescent idiopathic scoliosis (AIS) in multiple populations. For the first time, rs1322330 located in the putative promoter region of LBX1 was found significantly associated with AIS in the Chinese population [p = 6.08 × 10–14, odds ratio (OR) = 1.42, 95% confidence interval of 1.03–1.55]. Moreover, the luciferase assay and electrophoretic mobility shift assay supported that the allele A of rs1322330 could down-regulate the expression of LBX1 in the paraspinal muscles of AIS. In addition, silencing LBX1 in the myosatellite cells resulted in significantly inhibited cell viability and myotube formation, which supported an essential role of LBX1 in muscle development of AIS. To summarize, rs1322330 may be a novel functional SNP regulating the expression of LBX1, which was involved in the etiology of AIS possibly via regulation of myogenesis in the paraspinal muscles.
Regeneration of Planarian Auricles and Reestablishment of Chemotactic Ability
Authors: Almazan Eugene Matthew P. , Ryan Joseph F. , Rouhana Labib
Published: December 2021

Detection of chemical stimuli is crucial for living systems and also contributes to quality of life in humans. Since loss of olfaction becomes more prevalent with aging, longer life expectancies have fueled interest in understanding the molecular mechanisms behind the development and maintenance of chemical sensing. Planarian flatworms possess an unsurpassed ability for stem cell-driven regeneration that allows them to restore any damaged or removed part of their bodies. This includes anteriorly-positioned lateral flaps known as auricles, which have long been thought to play a central role in chemotaxis. The contribution of auricles to the detection of positive chemical stimuli was tested in this study usingGirardia dorotocephala, a North American planarian species known for its morphologically prominent auricles. Behavioral experiments staged under laboratory conditions revealed that removal of auricles by amputation leads to a significant decrease in the ability of planarians to find food. However, full chemotactic capacity is observed as early as 2 days post-amputation, which is days prior from restoration of auricle morphology, but correlative with accumulation of ciliated cells in the position of auricle regeneration. Planarians subjected to x-ray irradiation prior to auricle amputation were unable to restore auricle morphology, but were still able to restore chemotactic capacity. These results indicate that although regeneration of auricle morphology requires stem cells, some restoration of chemotactic ability can still be achieved in the absence of normal auricle morphology, corroborating with the initial observation that chemotactic success is reestablished 2-days post-amputation in our assays. Transcriptome profiles of excised auricles were obtained to facilitate molecular characterization of these structures, as well as the identification of genes that contribute to chemotaxis and auricle development. A significant overlap was found between genes with preferential expression in auricles ofG. dorotocephalaand genes with reduced expression uponSoxB1knockdown inSchmidtea mediterranea, suggesting thatSoxB1has a conserved role in regulating auricle development and function. Models that distinguish between possible contributions to chemotactic behavior obtained from cellular composition, as compared to anatomical morphology of the auricles, are discussed.
It Cuts Both Ways: An Annelid Model System for the Study of Regeneration in the Laboratory and in the Classroom
Authors: Martinez Acosta Veronica G. , Arellano-Carbajal Fausto , Gillen Kathy , Tweeten Kay A. , Zattara Eduardo E.
Published: December 2021

The mechanisms supporting regeneration and successful recovery of function have fascinated scientists and the general public for quite some time, with the earliest description of regeneration occurring in the 8th century BC through the Greek mythological story of Prometheus. While most animals demonstrate the capacity for wound-healing, the ability to initiate a developmental process that leads to a partial or complete replacement of a lost structure varies widely among animal taxa. Variation also occurs within single species based on the nature and location of the wound and the developmental stage or age of the individual. Comparative studies of cellular and molecular changes that occur both during, and following, wound healing may point to conserved genomic pathways among animals of different regenerative capacity. Such insights could revolutionize studies within the field of regenerative medicine. In this review, we focus on several closely related species of Lumbriculus (Clitellata: Lumbriculidae), as we present a case for revisiting the use of an annelid model system for the study of regeneration. We hope that this review will provide a primer to Lumbriculus biology not only for regeneration researchers but also for STEM teachers and their students.
Mechanisms of Non-Vesicular Exchange of Lipids at Membrane Contact Sites: Of Shuttles, Tunnels and, Funnels
Authors: Egea Pascal F.
Published: December 2021

Eukaryotic cells are characterized by their exquisite compartmentalization resulting from a cornucopia of membrane-bound organelles. Each of these compartments hosts a flurry of biochemical reactions and supports biological functions such as genome storage, membrane protein and lipid biosynthesis/degradation and ATP synthesis, all essential to cellular life. Acting as hubs for the transfer of matter and signals between organelles and throughout the cell, membrane contacts sites (MCSs), sites of close apposition between membranes from different organelles, are essential to cellular homeostasis. One of the now well-acknowledged function of MCSs involves the non-vesicular trafficking of lipids; its characterization answered one long-standing question of eukaryotic cell biology revealing how some organelles receive and distribute their membrane lipids in absence of vesicular trafficking. The endoplasmic reticulum (ER) in synergy with the mitochondria, stands as the nexus for the biosynthesis and distribution of phospholipids (PLs) throughout the cell by contacting nearly all other organelle types. MCSs create and maintain lipid fluxes and gradients essential to the functional asymmetry and polarity of biological membranes throughout the cell. Membrane apposition is mediated by proteinaceous tethers some of which function as lipid transfer proteins (LTPs). We summarize here the current state of mechanistic knowledge of some of the major classes of LTPs and tethers based on the available atomic to near-atomic resolution structures of several “model” MCSs from yeast but also in Metazoans; we describe different models of lipid transfer at MCSs and analyze the determinants of their specificity and directionality. Each of these systems illustrate fundamental principles and mechanisms for the non-vesicular exchange of lipids between eukaryotic membrane-bound organelles essential to a wide range of cellular processes such as at PL biosynthesis and distribution, lipid storage, autophagy and organelle biogenesis.
HO-1 in Bone Biology: Potential Therapeutic Strategies for Osteoporosis
Authors: Zhou Xueman , Yuan Wenxiu , Xiong Xin , Zhang Zhenzhen , Liu Jiaqi , Zheng Yingcheng , Wang Jun , Liu Jin
Published: December 2021

Osteoporosis is a prevalent bone disorder characterized by bone mass reduction and deterioration of bone microarchitecture leading to bone fragility and fracture risk. In recent decades, knowledge regarding the etiological mechanisms emphasizes that inflammation, oxidative stress and senescence of bone cells contribute to the development of osteoporosis. Studies have demonstrated that heme oxygenase 1 (HO-1), an inducible enzyme catalyzing heme degradation, exhibits anti-inflammatory, anti-oxidative stress and anti-apoptosis properties. Emerging evidence has revealed that HO-1 is critical in the maintenance of bone homeostasis, making HO-1 a potential target for osteoporosis treatment. In this Review, we aim to provide an introduction to current knowledge of HO-1 biology and its regulation, focusing specifically on its roles in bone homeostasis and osteoporosis. We also examine the potential of HO-1-based pharmacological therapeutics for osteoporosis and issues faced during clinical translation.
Septin Assembly and Remodeling at the Cell Division Site During the Cell Cycle
Authors: Marquardt Joseph , Chen Xi , Bi Erfei
Published: December 2021

The septin family of proteins can assemble into filaments that further organize into different higher order structures to perform a variety of different functions in different cell types and organisms. In the budding yeast Saccharomyces cerevisiae, the septins localize to the presumptive bud site as a cortical ring prior to bud emergence, expand into an hourglass at the bud neck (cell division site) during bud growth, and finally “split” into a double ring sandwiching the cell division machinery during cytokinesis. While much work has been done to understand the functions and molecular makeups of these structures, the mechanisms underlying the transitions from one structure to another have largely remained elusive. Recent studies involving advanced imaging and in vitro reconstitution have begun to reveal the vast complexity involved in the regulation of these structural transitions, which defines the focus of discussion in this mini-review.
RETRACTED: Taguchi-Assisted Optimization Technique and Density Functional Theory for Green Synthesis of a Novel Cu-MOF Derived From Caffeic Acid and Its Anticancerious Activities
Authors: Zeraati Malihe , Mohammadi Ali , Vafaei Somayeh , Chauhan Narendra Pal Singh , Sargazi Ghasem
Published: December 2021

In this paper, we have reported an innovative greener method for developing copper-metal organic frameworks (Cu-MOFs) using caffeic acid (CA) as a linker extracted from Satureja hortensis using ultrasonic bath. The density functional theory is used to discuss the Cu-MOF-binding reaction mechanism. In order to achieve a discrepancy between the energy levels of the interactive precursor orbitals, the molecules have been optimized using the B3LYP/6–31G method. The Taguchi method was used to optimize the key parameters for the synthesis of Cu-MOF. FT-IR, XRD, nitrogen adsorption, and SEM analyses are used to characterize it. The adsorption/desorption and SEM analyses suggested that Cu-MOF has a larger surface area of 284.94 m2/g with high porosity. Cu-MOF has shown anticancer activities against the human breast cancer (MDA-MB-468) cell lines, and it could be a potent candidate for clinical applications.
3D Printing of Solvent-Free Supramolecular Polymers
Authors: Rupp Harald , Binder Wolfgang H.
Published: December 2021

Additive manufacturing has significantly changed polymer science and technology by engineering complex material shapes and compositions. With the advent of dynamic properties in polymeric materials as a fundamental principle to achieve, e.g., self-healing properties, the use of supramolecular chemistry as a tool for molecular ordering has become important. By adjusting molecular nanoscopic (supramolecular) bonds in polymers, rheological properties, immanent for 3D printing, can be adjusted, resulting in shape persistence and improved printing. We here review recent progress in the 3D printing of supramolecular polymers, with a focus on fused deposition modelling (FDM) to overcome some of its limitations still being present up to date and open perspectives for their application.
Inorganic Nanozymes: Prospects for Disease Treatments and Detection Applications
Authors: Wang Peng , Min Dongyu , Chen Guoyou , Li Minghui , Tong Liquan , Cao Yonggang
Published: December 2021

In recent years, with the development of nanomaterials, a slice of nanomaterials has been demonstrated to possess high catalytic activity similar to natural enzymes and counter the dilemmas including easy inactivation and low yield natural of enzymes, which are labeled as nanozymes. The catalytic activity of nanozymes could be easily regulated by size, structure, surface modification and other factors. In comparison with natural enzymes, nanozymes featured with a more stable structure, economical preparation and preservation, diversity of functions and adjustable catalytic activity, thus becoming the potentially ideal substitute for natural enzymes. Generally, the are mainly three types containing metal oxide nanozymes, noble metal nanozymes and carbon-based nanozymes, owing various applications in biomedical, energy and environmental fields. In this review, to summarize the recent representative applications of nanozymes, and potentially explore the scientific problems in this field at the same time, we are going to discuss the catalytic mechanisms of diverse nanozymes, with the emphasis on their applications in the fields of tumor therapy, anti-inflammatory and biosensing, hoping to help and guide the future development of nanozymes.
Ferritin Conjugates With Multiple Clickable Amino Acids Encoded by C-Terminal Engineered Pyrrolysyl-tRNA Synthetase
Authors: Wang Yi-Hui , Jian Mu-Lung , Chen Pei-Jung , Tsou Jo-Chu , Truong Le P. , Wang Yane-Shih
Published: December 2021

This study reports the application of expanding genetic codes in developing protein cage-based delivery systems. The evolved Methanosarcina mazei pyrrolysyl-tRNA synthetase (PylRS)•tRNAPyl pairs derived from directed evolution are examined to probe their recognition for para-substituted phenylalanine analogs. The evolved MmPylRS, AzFRS, harboring a wide range of substrates, is further engineered at the C-terminal region into another variant, AzFRS-MS. AzFRS-MS shows suppression of the elevated sfGFP protein amount up to 10 TAG stop codons when charging p-azido-l-phenylalanine (AzF, 4), which allows the occurrence of click chemistry. Since protein nanocages used as drug delivery systems that encompass multiple drugs through a site-specific loading approach remain largely unexplored, as a proof of concept, the application of AzFRS-MS for the site-specific incorporation of AzF on human heavy chain ferritin (Ftn) is developed. The Ftn-4 conjugate is shown to be able to load multiple fluorescence dyes or a therapeutic agent, doxorubicin (Dox), through the strain-promoted azide-alkyne cycloaddition (SPAAC) click reaction. Aiming to selectively target Her2+ breast cancer cells, Ftn-4-DOX conjugates fused with a HER2 receptor recognition peptide, anti-Her2/neu peptide (AHNP), is developed and demonstrated to be able to deliver Dox into the cell and to prolong the drug release. This work presents another application of evolved MmPylRS systems, whose potential in developing a variety of protein conjugates is noteworthy.
Targeted On-Demand Screening of Pesticide Panel in Soil Runoff
Authors: Dhamu Vikram Narayanan , Sukumar Suhashine , Kadambathil Crisvin Sajee , Muthukumar Sriram , Prasad Shalini
Published: December 2021

Using pesticides is a common agricultural and horticultural practice to serve as a control against weeds, fungi, and insects in plant systems. The application of these chemical agents is usually by spraying them on the crop or plant. However, this methodology is not highly directional, and so only a fraction of the pesticide actually adsorbs onto the plant, and the rest seeps through into the soil base contaminating its composition and eventually leaching into groundwater sources. Electrochemical sensors which are more practical for in situ analysis used for pesticide detection in soil runoff systems are still in dearth, while the ones published in the literature are attributed with complex sensor modification/functionalization and preprocessing of samples. Hence, in this work, we present a highly intuitive electroanalytical sensor approach toward rapid (10 min), on-demand screening of commonly used pesticides—glyphosate and atrazine—in soil runoff. The proposed sensor functions based on the affinity biosensing mechanism driven via thiol cross-linker and antibody receptors that holistically behaves as a recognition immunoassay stack that is specific and sensitive to track test pesticide analytes. Then, this developed sensor is integrated further to create a pesticide-sensing ecosystem using a front-end field-deployable smart device. The method put forward in this work is compared and validated against a standard laboratory potentiostat instrument to determine efficacy, feasibility, and robustness for a point-of-use (PoU) setting yielding LoD levels of 0.001 ng/ml for atrazine and 1 ng/ml for glyphosate. Also, the ML model integration resulted in an accurate prediction rate of ≈80% in real soil samples. Therefore, a universal pesticide screening analytical device is designed, fabricated, and tested for pesticide assessment in real soil runoff samples.
Distinct Microbial Communities in Dilated Cardiomyopathy Explanted Hearts Are Associated With Different Myocardial Rejection Outcomes
Authors: Pereira Jaqueline de Jesus , Ikegami Renata Nishiyama , Kawakami Joyce Tiyeko , Garavelo Shérrira Menezes , Reis Marcia Martins , Palomino Suely Aparecida Pinheiro , Mangini Sandrigo , Moreno Camila Rodrigues , Barros Samar Freschi de , Souza Aline Rodrigues , Higuchi Maria de Lourdes
Published: December 2021

Background

Idiopathic dilated cardiomyopathy (IDCM) myocardial inflammation may be associated with external triggering factors such as infectious agents. Here, we searched if moderate/severe heart transplantation rejection is related to the presence of myocardial inflammation in IDCM explanted hearts, associated with microbial communities.

Method

Receptor myocardial samples from 18 explanted hearts were separated into groups according to post-transplant outcome: persistent moderate rejection (PMR; n = 6), moderate rejection (MR; n = 7) that regressed after pulse therapy, and no rejection (NR; n = 5)/light intensity rejection. Inflammation was quantified through immunohistochemistry (IHC), and infectious agents were evaluated by IHC, molecular biology, in situ hybridization technique, and transmission electron microscopy (TEM).

Results

NR presented lower numbers of macrophages, as well as B cells (p = 0.0001), and higher HLA class II expression (p ≤ 0.0001). PMR and MR showed higher levels of Mycoplasma pneumoniae (p = 0.003) and hepatitis B core (p = 0.0009) antigens. NR presented higher levels of parvovirus B19 (PVB19) and human herpes virus 6 (HHV6) and a positive correlation between Borrelia burgdorferi (Bb) and enterovirus genes. Molecular biology demonstrated the presence of M. pneumoniae, Bb, HHV6, and PVB19 genes in all studied groups. TEM revealed structures compatible with the cited microorganisms.

Conclusions

This initial study investigating on infectious agents and inflammation in the IDCM explanted hearts showed that the association between M. pneumoniae and hepatitis B core was associated with a worse outcome after HT, represented by MR and PMR, suggesting that different IDCM microbial communities may be contributing to post-transplant myocardial rejection.
Fighting Staphylococcus epidermidis Biofilm-Associated Infections: Can Iron Be the Key to Success?
Authors: Oliveira Fernando , Rohde Holger , Vilanova Manuel , Cerca Nuno
Published: December 2021

Staphylococcus epidermidis is one of the most important commensal microorganisms of human skin and mucosae. However, this bacterial species is also the cause of severe infections in immunocompromised patients, specially associated with the utilization of indwelling medical devices, that often serve as a scaffold for biofilm formation. S. epidermidis strains are often multidrug resistant and its association with biofilm formation makes these infections hard to treat. Their remarkable ability to form biofilms is widely regarded as its major pathogenic determinant. Although a significant amount of knowledge on its biofilm formation mechanisms has been achieved, we still do not understand how the species survives when exposed to the host harsh environment during invasion. A previous RNA-seq study highlighted that iron-metabolism associated genes were the most up-regulated bacterial genes upon contact with human blood, which suggested that iron acquisition plays an important role in S. epidermidis biofilm development and escape from the host innate immune system. In this perspective article, we review the available literature on the role of iron metabolism on S. epidermidis pathogenesis and propose that exploiting its dependence on iron could be pursued as a viable therapeutic alternative.
Persistent Uncertainties in Ocean Net Primary Production Climate Change Projections at Regional Scales Raise Challenges for Assessing Impacts on Ecosystem Services
Authors: Tagliabue Alessandro , Kwiatkowski Lester , Bopp Laurent , Butenschön Momme , Cheung William , Lengaigne Matthieu , Vialard Jerome
Published: December 2021

Ocean net primary production (NPP) results from CO2 fixation by marine phytoplankton, catalysing the transfer of organic matter and energy to marine ecosystems, supporting most marine food webs, and fisheries production as well as stimulating ocean carbon sequestration. Thus, alterations to ocean NPP in response to climate change, as quantified by Earth system model experiments conducted as part of the 5th and 6th Coupled Model Intercomparison Project (CMIP5 and CMIP6) efforts, are expected to alter key ecosystem services. Despite reductions in inter-model variability since CMIP5, the ocean components of CMIP6 models disagree roughly 2-fold in the magnitude and spatial distribution of NPP in the contemporary era, due to incomplete understanding and insufficient observational constraints. Projections of NPP change in absolute terms show large uncertainty in CMIP6, most notably in the North Atlantic and the Indo-Pacific regions, with the latter explaining over two-thirds of the total inter-model uncertainty. While the Indo-Pacific has previously been identified as a hotspot for climate impacts on biodiversity and fisheries, the increased inter-model variability of NPP projections further exacerbates the uncertainties of climate risks on ocean-dependent human communities. Drivers of uncertainty in NPP changes at regional scales integrate different physical and biogeochemical factors that require more targeted mechanistic assessment in future studies. Globally, inter-model uncertainty in the projected changes in NPP has increased since CMIP5, which amplifies the challenges associated with the management of associated ecosystem services. Notably, this increased regional uncertainty in the projected NPP change in CMIP6 has occurred despite reduced uncertainty in the regional rates of NPP for historical period. Improved constraints on the magnitude of ocean NPP and the mechanistic drivers of its spatial variability would improve confidence in future changes. It is unlikely that the CMIP6 model ensemble samples the complete uncertainty in NPP, with the inclusion of additional mechanistic realism likely to widen projections further in the future, especially at regional scales. This has important consequences for assessing ecosystem impacts. Ultimately, we need an integrated mechanistic framework that considers how NPP and marine ecosystems respond to impacts of not only climate change, but also the additional non-climate drivers.
Variability of Tropical Cyclone Frequency Over the Western North Pacific in 2018–2020
Authors: Ogata Tomomichi , Baba Yuya
Published: December 2021

In this study, we examine the tropical cyclone (TC) activity over the western North Pacific (WNP) in 2018–2020 and its relationship with planetary scale convection and circulation anomalies, which play an important role for TC genesis. To determine the sea surface temperature (SST)-forced atmospheric variability, atmospheric general circulation model (AGCM) ensemble simulations are executed along with the observed SST. For AGCM experiments, we use two different convection schemes to examine uncertainty in convective parameterization and robustness of simulated atmospheric response. The observed TC activity and genesis potential demonstrated consistent features. In our AGCM ensemble simulations, the updated convection scheme improves the simulation ability of observed genesis potential as well as planetary scale convection and circulation features, e.g., in September–October–November (SON), a considerable increase in the genesis potential index over the WNP in SON 2018, WNP in SON 2019, and South China Sea (SCS) in SON 2020, which were not captured in the Emanuel scheme, have been simulated in the updated convection scheme.
Biocatalytic Reductive Amination by Native Amine Dehydrogenases to Access Short Chiral Alkyl Amines and Amino Alcohols
Authors: Ducrot Laurine , Bennett Megan , Caparco Adam A. , Champion Julie A. , Bommarius Andreas S. , Zaparucha Anne , Grogan Gideon , Vergne-Vaxelaire Carine
Published: December 2021

Small optically active molecules, and more particularly short-chain chiral amines, are key compounds in the chemical industry and precursors of various pharmaceuticals. Their chemo-biocatalytic production on a commercial scale is already established, mainly through lipase-catalyzed resolutions leading to ChiPros™ products among others. Nevertheless, their biocatalytic synthesis remains challenging for very short-chain C4 to C5 amines due to low enantiomeric excess. To complement the possibilities recently offered by transaminases, this work describes alternative biocatalytic access using amine dehydrogenases (AmDHs). Without any protein engineering, some of the already described wild-type AmDHs (CfusAmDH, MsmeAmDH, MicroAmDH, and MATOUAmDH2) were shown to be efficient for the synthesis of hydroxylated or unfunctionalized small 2-aminoalkanes. Conversions up to 97.1% were reached at 50 mM, and moderate to high enantioselectivities were obtained, especially for (S)-1-methoxypropan-2-amine (98.1%), (S)-3-aminobutan-1-ol (99.5%), (3S)-3-aminobutan-2-ol (99.4%), and the small (S)-butan-2-amine (93.6%) with MsmeAmDH. Semi-preparative scale-up experiments were successfully performed at 150 mM substrate concentrations for the synthesis of (S)-butan-2-amine and (S)-1-methoxypropan-2-amine, the latter known as “(S)-MOIPA”. Modeling studies provided some preliminary results explaining the basis for the challenging discrimination between similarly sized substituents in the active sites of these enzymes.
Identification, Characterization, and In Silico Analysis of New Imine Reductases From Native Streptomyces Genomes
Authors: Iglesias César , Tijman Ariel , López Gonzalo , Lapaz María Inés , Pianzzola María Julia , Panizza Paola , Rodríguez Giordano Sonia
Published: December 2021

The development of biocatalytic tools for the synthesis of optically pure amines has been the focus of abundant research in recent years. Among other enzymes, imine reductases have attracted much attention associated with the possibility of attaining chiral secondary amines. Furthermore, the reductive aminase activity associated with some of these enzymes has facilitated the production of optically pure amines from a prochiral ketone, a transformation that opens doors to an incredible array of products. In this work, the genomes from native Streptomyces strains isolated in our lab have been explored on the search for novel imine reductases. Application of different structural criteria and sequence motif filters allowed the identification of two novel enzymes, Ss-IRED_S and Ss-IRED_R. While the former presented outstanding activity towards bulky cyclic imine substrates, the latter presented reductive aminase activity with the assayed ketones. A bioinformatic analysis based on modeling and docking studies was performed in order to explain the differences in enzyme activity, searching for additional criteria that could be used to analyze enzyme candidates in silico, providing additional tools for enzyme selection for a particular application. Our findings suggest that imine reductase activity could be predicted by this analysis, overall accounting for the number of docking positions that meet the catalytic requirements.
Perceptions of the Cardiologists and Oncologists: Initial Step for Establishing Cardio-Oncology Service
Authors: Farhan Hasan Ali , Yaseen Israa Fadhil
Published: December 2021

Background: Over the last years, there was no established cardio-oncology service in Iraq and no firm data about the incidence of cardiovascular disease (CVD) among patients with cancer. As an initial step, we decided to conduct a national cardio-oncology online survey for cardiologists, oncologists, and their residents which would help us to understand the expected prevalence, problems, and readiness for collaboration between the two specialties.

Objectives: For evaluating the current national practice in the cardiology and oncology specialty fields and to identify the hidden gaps associated with the development or worsening of CVD among patients with cancer.

Methods: An online survey including 19-question for cardiologists/cardiology residents (CCRs) and 30-question for oncologists/oncology residents (OORs) about cardio-oncology service was sent to them including all Iraqi cities using Google document form during December 2020.

Results: The total number of responses was 164, mainly 62.2% from CCRs while 37.8% from OORs. Hypertension was the main baseline risk factor (71%). A 77.5% of CCRs prescribe cardiovascular drugs vs. 35.5% by OORs. About 76.5% of CCRs and 79% of OORs are facing difficulties in the management of patients with cancer with established CVD. CVD was the leading cause of both hospitalization (30.7%) and mortality (48.4%). About 62.8% of CCRs and 64.5% of OORs have an interest to work in cardio-oncology service.

Conclusion: Based on the perception of cardiologists and oncologists, CVD is the main cause of hospitalization and mortality among patients with cancer. High interest among CCRs and OORs to work in cardio-oncology service. Positive initiatives are available to take the action plan in this emerging field.
Association Between 2D- and 3D-Speckle-Tracking Longitudinal Strain and Cardiovascular Magnetic Resonance Evidence of Diffuse Myocardial Fibrosis in Heart Transplant Recipients
Authors: Sun Wei , Shen Xuehua , Wang Jing , Zhu Shuangshuang , Zhang Yanting , Wu Chun , Xie Yuji , Yang Yun , Dong Nianguo , Wang Guohua , Li Yuman , Lv Qing , Liang Bo , Zhang Li , Xie Mingxing
Published: December 2021

Objective: This study aimed to: (1) evaluate the association between myocardial fibrosis (MF) quantified by extracellular volume fraction (ECV) and myocardial strain measured by two-dimensional (2D)- and three-dimensional speckle-tracking echocardiography (3D-STE) and (2) further investigate which strain parameter measured by 2D- and 3D-STE is the more robust predictor of MF in heart transplant (HT) recipients.

Methods: A total of 40 patients with HT and 20 healthy controls were prospectively enrolled. Left ventricular (LV)-global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were measured by 2D- and 3D-STE. LV diffuse MF was defined by cardiovascular magnetic resonance (CMR)-ECV.

Results: The HT recipients had a significantly higher native T1 and ECV than healthy controls (1043.8 ± 34.0 vs. 999.7 ± 19.7 ms, p < 0.001; 26.6 ± 2.7 vs. 24.3 ± 1.8%, p = 0.02). The 3D- and 2D-STE-LVGLS and LVGCS were lower (p < 0.005) in the HT recipients than in healthy controls. ECV showed a moderate correlation with 2D-LVGLS (r = 0.53, p = 0.002) and 3D-LVGLS (r = 0.60, p < 0.001), but it was not correlated with 2D or 3D-LVGCS, or LVGRS. Furthermore, 3D-LVGLS and 2D-LVGLS had a similar correlation with CMR-ECV (r = 0.60 vs. 0.53, p = 0.670). A separate stepwise multivariate linear analysis showed that both the 2D-LVGLS (β = 0.39, p = 0.019) and 3D-LVGLS (β = 0.54, p < 0.001) were independently associated with CMR-ECV.

Conclusion: CMR marker of diffuse MF was present in asymptomatic patients with HT and appeared to be associated with decreased myocardial strain by echocardiography. Both the 2D- and 3D-LVGLS were independently correlated with diffuse LVMF, which may provide an alternative non-invasive tool for monitoring the development of adverse fibrotic remodeling during the follow-up of HT recipients.
Pediatric Acute Myocarditis With Short-Term Outcomes and Factors for Extracorporeal Membrane Oxygenation: A Single-Center Retrospective Cohort Study in Vietnam
Authors: Tuan Ta Anh , Xoay Tran Dang , Phuc Phan Huu , Hung Dau Viet , Dung Nguyen Trong , Truong Nguyen Ly Thinh , Thuan Nguyen Van , Dien Tran Minh
Published: December 2021

Objective: Data on the management and outcomes of acute myocarditis treated with extracorporeal membrane oxygenation (ECMO) among low- and middle-income countries are limited. This study aimed to determine the short-term outcomes and also identify factors associated with ECMO use among children with acute myocarditis at a tertiary children's hospital in Vietnam.

Methods: A single-center, retrospective observational study was conducted between January 2016 and February 2021. Pediatric patients with acute myocarditis, aged 1 month to 16 years, were included.

Results: In total, 54 patients (male, 46%; median age, 7 years) with acute myocarditis were included; 37 of them received ECMO support. Thirty percent (16/54) of the patients died, and 12 of them received ECMO. Laboratory variables that differed between survivors and non-survivors included median left ventricular ejection fraction (LVEF) at 48 h (42 vs. 25%; p = 0.001), platelet count (304 g/L [interquartile range (IQR): 243–271] vs. 219 g/L [IQR: 167–297]; p = 0.014), and protein (60 g/dl [IQR: 54–69] vs. 55 [IQR: 50–58]; p = 0.025). Among patients who received ECMO, compared with the survivors, non-survivors had a low LVEF at 48 h (odds ratio (OR), 0.8; 95% confidence interval (CI): 0.6–0.9; p = 0.006) and high vasoactive-inotropic score (OR, 1.0; 95% CI: 1.0–1.0; p = 0.038) and lactate (OR, 2.8; 95% CI, 1.2–6.1; p = 0.013) at 24 h post-ECMO.

Conclusions: The case fatality rate among children with acute myocarditis was 30 and 32% among patients requiring ECMO support. Arrhythmia was an indicator for ECMO in patients with cardiogenic shock.
Lower Masticatory Performance Is a Risk for the Development of the Metabolic Syndrome: The Suita Study
Authors: Fushida Shuri , Kosaka Takayuki , Nakai Michikazu , Kida Momoyo , Nokubi Takashi , Kokubo Yoshihiro , Watanabe Makoto , Miyamoto Yoshihiro , Ono Takahiro , Ikebe Kazunori
Published: December 2021

Objectives: Declined masticatory function has recently been receiving attention as a risk factor for poor general health. The present longitudinal analysis was conducted to clarify the relationship between decreased masticatory performance and the development of the metabolic syndrome (MetS) in a general urban cohort in Japan.

Methods: We surveyed 599 participants (254 men, 345 women; mean age at baseline, 65.8 ± 7.8 years) who underwent physical health checkups in the Suita study. We evaluated masticatory performance at baseline using test gummy jelly and divided participants into two groups: a “Lower group,” comprising participants in the lower 25% of the masticatory performance at baseline; and a “Normal group,” comprising all others. We estimated hazard ratios (HRs) for the Lower group by using Cox proportional hazard regression analysis to develop the MetS and the components of the MetS at follow-up, adjusting for age, smoking status, and periodontal status.

Results: On Cox proportional hazard regression analysis, the multivariable adjusted hazard ratio for the development of the MetS in the Lower group was 2.24 (95% confidence interval, 1.12–4.50) in men. The multivariable adjusted hazard ratio for the development of high blood pressure was 3.12 (1.42–6.87), for high triglycerides was 2.82 (1.18–6.76), and for high fasting plasma glucose was 2.65 (1.00–7.00) in men.

Conclusions: Lower masticatory performance suggested to be a risk factor for the development of the MetS as well as MetS components such as high blood pressure, high triglycerides, and high fasting plasma glucose in Japanese men.
Normalized Cardiac Structure and Function in COVID-19 Survivors Late After Recovery
Authors: Gao Yi-Ping , Zhou Wei , Huang Pei-Na , Liu Hong-Yun , Bi Xiao-Jun , Zhu Ying , Sun Jie , Tang Qiao-Ying , Li Li , Zhang Jun , Sun Rui-Ying , Cheng Xue-Qing , Liu Ya-Ni , Deng You-Bin
Published: December 2021

Background: Coronavirus disease 2019 can result in myocardial injury in the acute phase. However, information on the late cardiac consequences of coronavirus disease 2019 (COVID-19) is limited.

Methods: We conducted a prospective observational cohort study to investigate the late cardiac consequences of COVID-19. Standard echocardiography and myocardial strain assessment were performed, and cardiac blood biomarkers were tested in 86 COVID-19 survivors 327 days (IQR 318–337 days) after recovery. Comparisons were made with 28 age-matched and sex-matched healthy controls and 30 risk factor-matched patients.

Results: There were no significant differences in all echocardiographic structural and functional parameters, including left ventricular (LV) global longitudinal strain, right ventricular (RV) longitudinal strain, LV end-diastolic volume, RV dimension, and the ratio of peak early velocity in mitral inflow to peak early diastolic velocity in the septal mitral annulus (E/e') among COVID-19 survivors, healthy controls and risk factor-matched controls. Even 26 patients with myocardial injury at admission did not have any echocardiographic structural and functional abnormalities. There were no significant differences among the three groups with respect to serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (cTnI).

Conclusion: This study showed that COVID-19 survivors, including those with myocardial injury at admission and those with severe and critical types of illness, do not have any echocardiographic evidence of cardiac structural and functional abnormalities 327 days after diagnosis.