bluuebunny/crossref_metadata_2025 huggingface dataset:
Processional Culture and Black Mobility in Maggie Washington's Wilmington
Authors: Gaddis Elijah
Published: January 2022

This article addresses changes in the built environment of the postbellum American South through an examination of the life histories, parade routes, and costuming practices of the Afro-Caribbean Jonkonnu masking tradition. I juxtapose the stories of two practitioners of the tradition across the color line in turn-of-the-twentieth-century Wilmington, North Carolina. Using a material culturally inflected approach to the study of landscapes, I use these two narratives to deepen the histories of African American processional cultures toward a longer time span and a more immersive, performer-oriented approach. Though few conventional objects of ornamentation and display from these practices survive, this article posits that an approach rooted in the materiality of landscape can help uncover festive cultures that have been understudied or undertheorized in more conventional historical approaches. Further, the ubiquitous presence of Jonkonnu and other Black processional traditions in the post-emancipation city suggests the importance of these and other objects, practices, and larger cultures of celebration in combating white supremacist culture.
Somewhere over the Rainbow
Authors: Grabher Barbara
Published: January 2022

Festival decorations are crucial indicators of the carnivalesque atmosphere of events as they capture celebratory experiences in tangible forms. Due to the strong presence of rainbow colors, LGBT+ Pride events provide fertile grounds for the discussion of decorative materials. While the acclaimed symbol of the rainbow is an expression of the LGBT+ community and their campaign for equality, the color combination is contested due to commercializing and appropriating forces. Next to altered color compositions highlighting particular identities and communities within the LGBT+ spectrum, explorations for alternative decorative patterns and visual expressions inform contemporary celebrations of equality during LGBT+ Pride events. In this article, I begin with a conceptual discussion of the carnivalesque notion, its inherent contradictions of subversion and discipline, and their expression in the form of decorative materials. Through an ethnographic study of the commemorative LGBT50 celebration in the context of Hull UK City of Culture 2017, I argue that alternative decorative approaches not only aesthetically influence the event but enable the reclaiming of the subversive atmospheres produced by the carnivalesque environment. Countering disciplining mechanisms of brand-like rainbow strategies, I outline how artistic practices negotiate innovative approaches to frame LGBT+ communities, identities, and celebrations.
Three-Dimensional Printing Strategies for Irregularly Shaped Cartilage Tissue Engineering: Current State and Challenges
Authors: Wang Hui , Wang Zhonghan , Liu He , Liu Jiaqi , Li Ronghang , Zhu Xiujie , Ren Ming , Wang Mingli , Liu Yuzhe , Li Youbin , Jia Yuxi , Wang Chenyu , Wang Jincheng
Published: January 2022

Although there have been remarkable advances in cartilage tissue engineering, construction of irregularly shaped cartilage, including auricular, nasal, tracheal, and meniscus cartilages, remains challenging because of the difficulty in reproducing its precise structure and specific function. Among the advanced fabrication methods, three-dimensional (3D) printing technology offers great potential for achieving shape imitation and bionic performance in cartilage tissue engineering. This review discusses requirements for 3D printing of various irregularly shaped cartilage tissues, as well as selection of appropriate printing materials and seed cells. Current advances in 3D printing of irregularly shaped cartilage are also highlighted. Finally, developments in various types of cartilage tissue are described. This review is intended to provide guidance for future research in tissue engineering of irregularly shaped cartilage.
Identification of Influential Modules Considering Design Change Impacts Based on Parallel Breadth-First Search and Bat Algorithm
Authors: Cheng Xianfu , Guo Zhihu , Ma Xiaotian , Yuan Tian
Published: January 2022

Modular design is a widely used strategy that meets diverse customer requirements. Close relationships exist between parts inside a module and loose linkages between modules in the modular products. A change of one part or module may cause changes of other parts or modules, which in turn propagate through a product. This paper aims to present an approach to analyze the associations and change impacts between modules and identify influential modules in modular product design. The proposed framework explores all possible change propagation paths (CPPs), and measures change impact degrees between modules. In this article, a design structure matrix (DSM) is used to express dependence relationships between parts, and change propagation trees of affected parts within module are constructed. The influence of the affected part in the corresponding module is also analyzed, and a reachable matrix is employed to determine reachable parts of change propagation. The parallel breadth-first algorithm is used to search propagation paths. The influential modules are identified according to their comprehensive change impact degrees that are computed by the bat algorithm. Finally, a case study on the grab illustrates the impacts of design change in modular products.
Effects of Revision Rod Position on Spinal Construct Stability in Lumbar Revision Surgery: A Finite Element Study
Authors: Tan Quan-Chang , Huang Jin-Feng , Bai Hao , Liu Zi-Xuan , Huang Xin-Yi , Zhao Xiong , Yang Zhao , Du Cheng-Fei , Lei Wei , Wu Zi-Xiang
Published: January 2022

Revision surgery (RS) is a necessary surgical intervention in clinical practice to treat spinal instrumentation–related symptomatic complications. Three constructs with different configurations have been applied in RS. One distinguishing characteristic of these configurations is that the revision rods connecting previous segments and revision segments are placed alongside, outside, or inside the previous rods at the level of facetectomy. Whether the position of the revision rod could generate mechanical disparities in revision constructs is unknown. The objective of this study was to assess the influence of the revision rod position on the construct after RS. A validated spinal finite element (FE) model was developed to simulate RS after previous instrumented fusion using a modified dual-rod construct (DRCm), satellite-rod construct (SRC), and cortical bone trajectory construct (CBTC). Thereafter, maximum von Mises stress (VMS) on the annulus fibrosus and cages and the ligament force of the interspinous ligament, supraspinous ligament, and ligamentum flavum under a pure moment load and a follower load in six directions were applied to assess the influence of the revision rod position on the revision construct. An approximately identical overall reducing tendency of VMS was observed among the three constructs. The changing tendency of the maximum VMS on the cages placed at L4-L5 was nearly equal among the three constructs. However, the changing tendency of the maximum VMS on the cage placed at L2-L3 was notable, especially in the CBTC under right bending and left axial rotation. The overall changing tendency of the ligament force in the DRCm, SRC, and CBTC was also approximately equal, while the ligament force of the CBTC was found to be significantly greater than that of the DRCm and SRC at L1-L2. The results indicated that the stiffness associated with the CBTC might be lower than that associated with the DRCm and SRC in RS. The results of the present study indicated that the DRCm, SRC, and CBTC could provide sufficient stabilization in RS. The CBTC was a less rigid construct. Rather than the revision rod position, the method of constructing spinal instrumentation played a role in influencing the biomechanics of revision.
Macrophage-Derived Exosomes Promote Bone Mesenchymal Stem Cells Towards Osteoblastic Fate Through microRNA-21a-5p
Authors: Liu Kun , Luo Xin , Lv Zhao-Yong , Zhang Yu-Jue , Meng Zhen , Li Jun , Meng Chun-Xiu , Qiang Hui-Fen , Hou Cai-Yao , Hou Lei , Liu Feng-Zhen , Zhang Bin
Published: January 2022

The effective healing of a bone defect is dependent on the careful coordination of inflammatory and bone-forming cells. In the current work, pro-inflammatory M1 and anti-inflammatory M2 macrophages were co-cultured with primary murine bone mesenchymal stem cells (BMSCs), in vitro, to establish the cross-talk among polarized macrophages and BMSCs, and as well as their effects on osteogenesis. Meanwhile, macrophages influence the osteogenesis of BMSCs through paracrine forms such as exosomes. We focused on whether exosomes of macrophages promote osteogenic differentiation. The results indicated that M1 and M2 polarized macrophage exosomes all can promote osteogenesis of BMSCs. Especially, M1 macrophage-derived exosomes promote osteogenesis of BMSCs through microRNA-21a-5p at the early stage of inflammation. This research helps to develop an understanding of the intricate interactions among BMSCs and macrophages, which can help to improve the process of bone healing as well as additional regenerative processes by local sustained release of exosomes.
Localizing Epileptic Foci Before Surgery in Patients With MRI-Negative Refractory Epilepsy Using Statistical Parameter Mapping and Three-Dimensional Stereotactic Surface Projection Based on 18F-FDG PET
Authors: Zhou Hailing , Zhang Wei , Tan Zhiqiang , Zhou Ziqing , Li Ying , Zhang Shaojuan , Zhang Lingling , Gan Jiefeng , Wu Huanhua , Tang Yongjin , Cheng Yong , Ling Xueying , Guo Qiang , Xu Hao
Published: January 2022

Patients with refractory epilepsy are not only free of seizures after resecting epileptic foci, but also experience significantly improved quality of life. Fluorine-18-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) is a promising avenue for detecting epileptic foci in patients with magnetic resonance imaging (MRI)-negative refractory epilepsy. However, the detection of epileptic foci by visual assessment based on 18F-FDG PET is often complicated by a variety of factors in clinical practice. Easy imaging methods based on 18F-FDG PET images, such as statistical parameter mapping (SPM) and three-dimensional stereotactic surface projection (3D-SSP), can objectively detect epileptic foci. In this study, the regions of surgical resection of patients with over 1 year follow-up and no seizures were defined as standard epileptic foci. We retrospectively analyzed the sensitivity of visual assessment, SPM and 3D-SSP based on 18F-FDG PET to detect epileptic foci in MRI-negative refractory epilepsy patients and obtained the sensitivities of visual assessment, SPM and 3D-SSP are 57, 70 and 60% respectively. Visual assessment combined with SPM or 3D-SSP can improve the sensitivity of detecting epileptic foci. The sensitivity was highest when the three methods were combined, but decreased consistency, in localizing epileptic foci. We conclude that SPM and 3D-SSP can be used as objective methods to detect epileptic foci before surgery in patients with MRI-negative refractory epilepsy. Visual assessment is the preferred method for PET image analysis in MRI-negative refractory epilepsy. When the visual assessment is inconsistent with the patient’s electroclinical information, SPM or 3D-SSP was further selected to assess the epileptic foci. If the combination of the two methods still fails to accurately locate the epileptic foci, comprehensive evaluation can be performed by combining the three methods.
Review on Strategies and Technologies for Exosome Isolation and Purification
Authors: Chen Jiaci , Li Peilong , Zhang Taiyi , Xu Zhipeng , Huang Xiaowen , Wang Ruiming , Du Lutao
Published: January 2022

Exosomes, a nano-sized subtype of extracellular vesicles secreted from almost all living cells, are capable of transferring cell-specific constituents of the source cell to the recipient cell. Cumulative evidence has revealed exosomes play an irreplaceable role in prognostic, diagnostic, and even therapeutic aspects. A method that can efficiently provide intact and pure exosomes samples is the first step to both exosome-based liquid biopsies and therapeutics. Unfortunately, common exosomal separation techniques suffer from operation complexity, time consumption, large sample volumes and low purity, posing significant challenges for exosomal downstream analysis. Efficient, simple, and affordable methods to isolate exosomes are crucial to carrying out relevant researches. In the last decade, emerging technologies, especially microfluidic chips, have proposed superior strategies for exosome isolation and exhibited fascinating performances. While many excellent reviews have overviewed various methods, a compressive review including updated/improved methods for exosomal isolation is indispensable. Herein, we first overview exosomal properties, biogenesis, contents, and functions. Then, we briefly outline the conventional technologies and discuss the challenges of clinical applications of these technologies. Finally, we review emerging exosomal isolation strategies and large-scale GMP production of engineered exosomes to open up future perspectives of next-generation Exo-devices for cancer diagnosis and treatment.
Post-Synthetic Enzymatic and Chemical Modifications for Novel Sustainable Polyesters
Authors: El-malek Fady Abd , Steinbüchel Alexander
Published: January 2022

Because of their biodegradability, compostability, compatibility and flexible structures, biodegradable polymers such as polyhydroxyalkanoates (PHA) are an important class of biopolymers with various industrial and biological uses. PHAs are thermoplastic polyesters with a limited processability due to their low heat resistance. Furthermore, due to their high crystallinity, some PHAs are stiff and brittle. These features result sometimes in very poor mechanical characteristics with low extension at break values which limit the application range of some natural PHAs. Several in vivo approaches for PHA copolymer modifications range from polymer production to enhance PHA-based material performance after synthesis. The methods for enzymatic and chemical polymer modifications are aiming at modifying the structures of the polyesters and thereby their characteristics while retaining the biodegradability. This survey illustrates the efficient use of enzymes and chemicals in post-synthetic PHA modifications, offering insights on these green techniques for modifying and improving polymer performance. Important studies in this sector will be reviewed, as well as chances and obstacles for their stability and hyper-production.
Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma
Authors: Xu Jiadai , Wang Yue , Wei Zheng , Zhuang Jingli , Li Jing , Sun Yifeng , Ren Liang , Wang Yawen , Li Panpan , Gu Shiyang , Zhang Yian , Jiang Jifeng , Chen Chen , Zhang Yu , Liu Peng
Published: January 2022

This study attempted to investigate how clonal structure evolves, along with potential regulatory networks, as a result of multiline therapies in relapsed/refractory multiple myeloma (RRMM). Eight whole exome sequencing (WES) and one single cell RNA sequencing (scRNA-seq) were performed in order to assess dynamic genomic changes in temporal consecutive samples of one RRMM patient from the time of diagnosis to death (about 37 months). The 63-year-old female patient who suffered from MM (P1) had disease progression (PD) nine times from July 2017 [newly diagnosed (ND)] to Aug 2020 (death), and the force to drive branching-pattern evolution of malignant PCs was found to be sustained. The mutant-allele tumor heterogeneity (MATH) and tumor mutation burden (TMB) initially exhibited a downward trend, which was then upward throughout the course of the disease. Various somatic single nucleotide variants (SNVs) that had disappeared after the previous treatment were observed to reappear in later stages. Chromosomal instability (CIN) and homologous recombination deficiency (HRD) scores were observed to be increased during periods of all progression, especially in the period of extramedullary plasmacytoma. Finally, in combination with WES and scRNA-seq of P1-PD9 (the nineth PD), the intro-heterogeneity and gene regulatory networks of MM cells were deciphered. As verified by the overall survival of MM patients in the MMRF CoMMpass and GSE24080 datasets, RUNX3 was identified as a potential driver for RRMM.
Impact of Sepsis on High-Density Lipoprotein Metabolism
Authors: Reisinger Alexander C. , Schuller Max , Sourij Harald , Stadler Julia T. , Hackl Gerald , Eller Philipp , Marsche Gunther
Published: January 2022

Background: High-density lipoproteins (HDL) are thought to play a protective role in sepsis through several mechanisms, such as promotion of steroid synthesis, clearing bacterial toxins, protection of the endothelial barrier, and antioxidant/inflammatory activities. However, HDL levels decline rapidly during sepsis, but the contributing mechanisms are poorly understood.

Methods/Aim: In the present study, we investigated enzymes involved in lipoprotein metabolism in sepsis and non-sepsis patients admitted to the intensive care unit (ICU).

Results: In 53 ICU sepsis and 25 ICU non-sepsis patients, we observed significant differences in several enzymes involved in lipoprotein metabolism. Lecithin-cholesterol acyl transferase (LCAT) activity, LCAT concentration, and cholesteryl transfer protein (CETP) activity were significantly lower, whereas phospholipid transfer activity protein (PLTP) and endothelial lipase (EL) were significantly higher in sepsis patients compared to non-sepsis patients. In addition, serum amyloid A (SAA) levels were increased 10-fold in sepsis patients compared with non-sepsis patients. Furthermore, we found that LCAT activity was significantly associated with ICU and 28-day mortality whereas SAA levels, representing a strong inflammatory marker, did not associate with mortality outcomes.

Conclusion: We provide novel data on the rapid and robust changes in HDL metabolism during sepsis. Our results clearly highlight the critical role of specific metabolic pathways and enzymes in sepsis pathophysiology that may lead to novel therapeutics.
Construction of a Novel Ferroptosis-Related Gene Signature of Atherosclerosis
Authors: Huang Tucheng , Wang Kangjie , Li Yuewei , Ye Yanchen , Chen Yangxin , Wang Jingfeng , Yao Chen
Published: January 2022

Atheroclerosis refers to a chronic inflammatory disease featured by the accumulation of fibrofatty lesions in the intima of arteries. Cardiovasular events associated with atherosclerosis remain the major causes of mortality worldwide. Recent studies have indicated that ferroptosis, a novel programmed cell death, might participate in the process of atherosclerosis. However, the ferroptosis landscape is still not clear. In this study, 59 genes associated with ferroptosis were ultimately identified in atherosclerosis in the intima. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for functional annotation. Through the construction of protein–protein interaction (PPI) network, five hub genes (TP53, MAPK1, STAT3, HMOX1, and PTGS2) were then validated histologically. The competing endogenous RNA (ceRNA) network of hub genes was ultimately constructed to explore the regulatory mechanism between lncRNAs, miRNAs, and hub genes. The findings provide more insights into the ferroptosis landscape and, potentially, the therapeutic targets of atherosclerosis.
Recent Advances in Single-Cell View of Mesenchymal Stem Cell in Osteogenesis
Authors: Shen Fangyuan , Shi Yu
Published: January 2022

Osteoblasts continuously replenished by osteoblast progenitor cells form the basis of bone development, maintenance, and regeneration. Mesenchymal stem cells (MSCs) from various tissues can differentiate into the progenitor cell of osteogenic lineage and serve as the main source of osteoblasts. They also respond flexibly to regenerative and anabolic signals emitted by the surrounding microenvironment, thereby maintaining bone homeostasis and participating in bone remodeling. However, MSCs exhibit heterogeneity at multiple levels including different tissue sources and subpopulations which exhibit diversified gene expression and differentiation capacity, and surface markers used to predict cell differentiation potential remain to be further elucidated. The rapid advancement of lineage tracing methods and single-cell technology has made substantial progress in the characterization of osteogenic stem/progenitor cell populations in MSCs. Here, we reviewed the research progress of scRNA-seq technology in the identification of osteogenic markers and differentiation pathways, MSC-related new insights drawn from single-cell technology combined with experimental technology, and recent findings regarding the interaction between stem cell fate and niche in homeostasis and pathological process.
Dendriplex-Impregnated Hydrogels With Programmed Release Rate
Authors: Apartsin Evgeny , Venyaminova Alya , Majoral Jean-Pierre , Caminade Anne-Marie
Published: January 2022

Hydrogels are biocompatible matrices for local delivery of nucleic acids; however, functional dopants are required to provide efficient delivery into cells. In particular, dendrimers, known as robust nucleic acid carriers, can be used as dopants. Herein, we report the first example of impregnating neutral hydrogels with siRNA–dendrimer complexes. The surface chemistry of dendrimers allows adjusting the release rate of siRNA-containing complexes. This methodology can bring new materials for biomedical applications.
Higher Light Extraction Efficiency in Organic Light-Emitting Devices by Employing 2D Periodic Corrugation
Authors: Bai Yu , Chuai Yahui , Wang Yang , Wang Yingzhi
Published: January 2022

Photons trapped in the form of waveguide (WG) modes associated with the organic–organic interface and in the form of surface plasmon polariton (SPP) modes associated with the metallic electrode–organic interface result in a large energy loss in organic light-emitting devices (OLEDs). Introducing gratings onto the metallic electrode is especially crucial for recovering the power lost to the associated SPP modes. In our research, we demonstrate the efficient outcoupling of SPP modes in TE mode by two-dimensional (2D) grating, which cannot excited in one-dimensional (1D) grating OLED. This causes a 62.5% increase in efficiency from 2D grating OLED than 1D grating OLED. The efficient outcoupling of the WG and SPP modes is verified by the numerical simulation of both the emission spectra and the field distribution.
One-Pot Synthesized Amorphous Cobalt Sulfide With Enhanced Electrochemical Performance as Anodes for Lithium-Ion Batteries
Authors: Ren Long-Long , Wang Lin-Hui , Qin Yu-Feng , Li Qiang
Published: January 2022

In order to solve the poor cycle stability and the pulverization of cobalt sulfides electrodes, a series of amorphous and crystalline cobalt sulfides were prepared by one-pot solvothermal synthesis through controlling the reaction temperatures. Compared to the crystalline cobalt sulfide electrodes, the amorphous cobalt sulfide electrodes exhibited superior electrochemical performance. The high initial discharge and charge capacities of 2,132 mAh/g and 1,443 mAh/g at 200 mA/g were obtained. The reversible capacity was 1,245 mAh/g after 200 cycles, which is much higher than the theoretical capacity. The specific capability was 815 mAh/g at 800 mA/g and increased to 1,047 mAh/g when back to 100 mA/g, indicating the excellent rate capability. The outstanding electrochemical performance of the amorphous cobalt sulfide electrodes could result from the unique characteristics of more defects, isotropic nature, and the absence of grain boundaries for amorphous nanostructures, indicating the potential application of amorphous cobalt sulfide as anodes for lithium-ion batteries.
Network-Like Platinum Nanosheets Enabled by a Calorific-Effect-Induced-Fusion Strategy for Enhanced Catalytic Hydrogenation Performance
Authors: Chen Ting-Wen , Pang Da-Wei , Kang Jian-Xin , Zhang Dong-Feng , Guo Lin
Published: January 2022

In this paper, we report the construction of network-like platinum (Pt) nanosheets based on Pt/reduced graphite oxide (Pt/rGO) hybrids by delicately utilizing a calorific-effect-induced-fusion strategy. The tiny Pt species first catalyzed the H2-O2 combination reaction. The released heat triggered the combustion of the rGO substrate under the assistance of the Pt species catalysis, which induced the fusion of the tiny Pt species into a network-like nanosheet structure. The loading amount and dispersity of Pt on rGO are found to be crucial for the successful construction of network-like Pt nanosheets. The as-prepared products present excellent catalytic hydrogenation activity and superior stability towards unsaturated bonds such as olefins and nitrobenzene. The styrene can be completely converted into phenylethane within 60 min. The turnover frequency (TOF) value of network-like Pt nanosheets is as high as 158.14 h−1, which is three times higher than that of the home-made Pt nanoparticles and among the highest value of the support-free bimetallic catalysts ever reported under similar conditions. Furthermore, the well dispersibility and excellent aggregation resistance of the network-like structure endows the catalyst with excellent recyclability. The decline of conversion could be hardly identified after five times recycling experiments.
Salivary Microbial Dysbiosis Is Associated With Peri-Implantitis: A Case-Control Study in a Brazilian Population
Authors: Pallos Debora , Sousa Vanessa , Feres Magda , Retamal-Valdes Belen , Chen Tsute , Curtis Mike , Boaventura Richardson Mondego , Tanaka Marcia Hiromi , Salomão Gustavo Vargas da Silva , Zanella Louise , Tozetto-Mendoza Tania Regina , Schwab Gabriela , Franco Lucas Augusto Moyses , Sabino Ester Cerdeira , Braz-Silva Paulo Henrique , Shibli Jamil Awad
Published: January 2022

Background and Objectives

The aim of this study was to examine the salivary microbiome in healthy peri-implant sites and those with peri-implantitis.

Methods

Saliva samples were collected from 21 participants with healthy peri-implant sites and 21 participants with peri-implantitis. The V4 hypervariable region of the 16S rRNA gene was sequenced using the Ion Torrent PGM System (Ion 318™ Chip v2 400). The NGS analysis and composition of the salivary microbiome were determined by taxonomy assignment. Downstream bioinformatic analyses were performed in QIIME (v 1.9.1).

Results

Clinical differences according to peri-implant condition status were found. Alpha diversity metrics revealed that the bacterial communities of participants with healthy peri-implant sites tended to have a richer microbial composition than individuals with peri-implantitis. In terms of beta diversity, bleeding on probing (BoP) may influence the microbial diversity. However, no clear partitioning was noted between the salivary microbiome of volunteers with healthy peri-implant sites or volunteers with peri-implantitis. The highest relative abundance of Stenotrophomonas, Enterococcus and Leuconostoc genus, and Faecalibacterium prausnitzii, Haemophilus parainfluenzae, Prevotella copri, Bacteroides vulgatus, and Bacteroides stercoris bacterial species was found in participants with peri-implantitis when compared with those with healthy peri-implant sites.

Conclusion

Differences in salivary microbiome composition were observed between patients with healthy peri-implant sites and those with peri-implantitis. BoP could affect the diversity (beta diversity) of the salivary microbiome.
The Role of Candida albicans Virulence Factors in the Formation of Multispecies Biofilms With Bacterial Periodontal Pathogens
Authors: Satala Dorota , Gonzalez-Gonzalez Miriam , Smolarz Magdalena , Surowiec Magdalena , Kulig Kamila , Wronowska Ewelina , Zawrotniak Marcin , Kozik Andrzej , Rapala-Kozik Maria , Karkowska-Kuleta Justyna
Published: January 2022

Periodontal disease depends on the presence of different microorganisms in the oral cavity that during the colonization of periodontal tissues form a multispecies biofilm community, thus allowing them to survive under adverse conditions or facilitate further colonization of host tissues. Not only numerous bacterial species participate in the development of biofilm complex structure but also fungi, especially Candida albicans, that often commensally inhabits the oral cavity. C. albicans employs an extensive armory of various virulence factors supporting its coexistence with bacteria resulting in successful host colonization and propagation of infection. In this article, we highlight various aspects of individual fungal virulence factors that may facilitate the collaboration with the associated bacterial representatives of the early colonizers of the oral cavity, the bridging species, and the late colonizers directly involved in the development of periodontitis, including the “red complex” species. In particular, we discuss the involvement of candidal cell surface proteins—typical fungal adhesins as well as originally cytosolic “moonlighting” proteins that perform a new function on the cell surface and are also present within the biofilm structures. Another group of virulence factors considered includes secreted aspartic proteases (Sap) and other secreted hydrolytic enzymes. The specific structure of the candidal cell wall, dynamically changing during morphological transitions of the fungus that favor the biofilm formation, is equally important and discussed. The non-protein biofilm-composing factors also show dynamic variability upon the contact with bacteria, and their biosynthesis processes could be involved in the stability of mixed biofilms. Biofilm-associated changes in the microbe communication system using different quorum sensing molecules of both fungal and bacterial cells are also emphasized in this review. All discussed virulence factors involved in the formation of mixed biofilm pose new challenges and influence the successful design of new diagnostic methods and the application of appropriate therapies in periodontal diseases.
The Structural Basis of Babesia orientalis Lactate Dehydrogenase
Authors: Yu Long , Liu Qin , Luo Wanxin , Zhao Junlong , Alzan Heba F. , He Lan
Published: January 2022

Glycolytic enzymes play a crucial role in the anaerobic glycolysis of apicomplexan parasites for energy generation. Consequently, they are considered as potential targets for new drug development. Previous studies revealed that lactate dehydrogenase (LDH), a glycolytic enzyme, is a potential drug target in different parasites, such as Plasmodium, Toxoplasma, Cryptosporidium, and Piroplasma. Herein, in order to investigate the structural basis of LDH in Babesia spp., we determined the crystal structure of apo Babesia orientalis (Bo) LDH at 2.67-Å resolution in the space group P1. A five-peptide insertion appears in the active pocket loop of BoLDH to create a larger catalytic pocket, like other protozoa (except for Babesia microti LDH) and unlike its mammalian counterparts, and the absence of this extra insertion inactivates BoLDH. Without ligands, the apo BoLDH takes R-state (relaxed) with the active-site loop open. This feature is obviously different from that of allosteric LDHs in T-state (tense) with the active-site loop open. Compared with allosteric LDHs, the extra salt bridges and hydrogen bonds make the subunit interfaces of BoLDH more stable, and that results in the absence of T-state. Interestingly, BoLDH differs significantly from BmLDH, as it exhibits the ability to adapt quickly to the synthetic co-factor APAD+. In addition, the enzymatic activity of BoLDH was inhibited non-competitively by polyphenolic gossypol with a Ki value of 4.25 μM, indicating that BoLDH is sensitive to the inhibition of gossypol and possibly to its new derivative compounds. The current work provides the structural basis of BoLDH for the first time and suggests further investigation on the LDH structure of other Babesia spp. That knowledge would indeed facilitate the screening and designing of new LDH inhibitors to control the intracellular proliferation of Babesia spp.
Crystal Violet Staining Alone Is Not Adequate to Assess Synergism or Antagonism in Multi-Species Biofilms of Bacteria Associated With Bacterial Vaginosis
Authors: Castro Joana , Lima Ângela , Sousa Lúcia G. V. , Rosca Aliona S. , Muzny Christina A. , Cerca Nuno
Published: January 2022

Bacterial Vaginosis (BV) involves the presence of a multi-species biofilm adhered to vaginal epithelial cells, but its in-depth study has been limited due to the complexity of the bacterial community, which makes the design of in vitro models challenging. Perhaps the most common experimental technique to quantify biofilms is the crystal violet (CV) staining method. Despite its widespread utilization, the CV method is not without flaws. While biofilm CV quantification within the same strain in different conditions is normally accepted, assessing multi-species biofilms formation by CV staining might provide significant bias. For BV research, determining possible synergism or antagonism between species is a fundamental step for assessing the roles of individual species in BV development. Herein, we provide our perspective on how CV fails to properly quantify an in vitro triple-species biofilm composed of Gardnerella vaginalis, Fannyhessea (Atopobium) vaginae, and Prevotella bivia, three common BV-associated bacteria thought to play key roles in incident BV pathogenesis. We compared the CV method with total colony forming units (CFU) and fluorescence microscopy cell count methods. Not surprisingly, when comparing single-species biofilms, the relationship between biofilm biomass, total number of cells, and total cultivable cells was very different between each tested method, and also varied with the time of incubation. Thus, despite its wide utilization for single-species biofilm quantification, the CV method should not be considered for accurate quantification of multi-species biofilms in BV pathogenesis research.
MinION™ Nanopore Sequencing of Skin Microbiome 16S and 16S-23S rRNA Gene Amplicons
Authors: Rozas Miquel , Brillet François , Callewaert Chris , Paetzold Bernhard
Published: January 2022

Human skin microbiome dysbiosis can have clinical consequences. Characterizing taxonomic composition of bacterial communities associated with skin disorders is important for dermatological advancement in both diagnosis and novel treatments. This study aims to analyze and improve the accuracy of taxonomic classification of skin bacteria with MinION™ nanopore sequencing using a defined skin mock community and a skin microbiome sample. We compared the Oxford Nanopore Technologies recommended procedures and concluded that their protocols highly bias the relative abundance of certain skin microbiome genera, most notably a large overrepresentation of Staphylococcus and underrepresentation of Cutibacterium and Corynebacterium. We demonstrated that changes in the amplification protocols improved the accuracy of the taxonomic classification for these three main skin bacterial genera. This study shows that MinION™ nanopore could be an efficient technology for full-length 16S rRNA sequencing; however, the analytical advantage is strongly influenced by the methodologies. The suggested alternatives in the sample processing improved characterization of a complex skin microbiome community using MinION™ nanopore sequencing.
A Novel Tigecycline Adjuvant ML-7 Reverses the Susceptibility of Tigecycline-Resistant Klebsiella pneumoniae
Authors: Sun Lilan , Sun Lang , Li Xue , Hu Xinxin , Wang Xiukun , Nie Tongying , Zhang Youwen , You Xuefu
Published: January 2022

The increasing incidence of tigecycline resistance undoubtedly constitutes a serious threat to global public health. The combination therapies had become the indispensable strategy against this threat. Herein, 11 clinical tigecycline-resistant Klebsiella pneumoniae which mainly has mutations in ramR, acrR, or macB were collected for tigecycline adjuvant screening. Interestingly, ML-7 hydrochloride (ML-7) dramatically potentiated tigecycline activity. We further picked up five analogs of ML-7 and evaluated their synergistic activities with tigecycline by using checkerboard assay. The results revealed that ML-7 showed certain synergy with tigecycline, while other analogs exerted attenuated synergistic effects among tigecycline-resistant isolates. Thus, ML-7 was selected for further investigation. The results from growth curves showed that ML-7 combined with tigecycline could completely inhibit the growth of bacteria, and the time-kill analysis revealed that the combination exhibited synergistic bactericidal activities for tigecycline-resistant isolates during 24 h. The ethidium bromide (EtBr) efflux assay demonstrated that ML-7 could inhibit the functions of efflux pump. Besides, ML-7 disrupted the proton motive force (PMF) via increasing ΔpH, which in turn lead to the inhibition of the functions of efflux pump, reduction of intracellular ATP levels, as well as accumulation of ROS. All of which promoted the death of bacteria. And further transcriptomic analysis revealed that genes related to the mechanism of ML-7 mainly enriched in ABC transporters. Taken together, these results revealed the potential of ML-7 as a novel tigecycline adjuvant to circumvent tigecycline-resistant Klebsiella pneumoniae.
Shedding Light on Autophagy During Human Tuberculosis. A Long Way to Go
Authors: Pellegrini Joaquin Miguel , Tateosian Nancy Liliana , Morelli María Paula , García Verónica Edith
Published: January 2022

Immunity against Mycobacterium tuberculosis (Mtb) is highly complex, and the outcome of the infection depends on the role of several immune mediators with particular temporal dynamics on the host microenvironment. Autophagy is a central homeostatic mechanism that plays a role on immunity against intracellular pathogens, including Mtb. Enhanced autophagy in macrophages mediates elimination of intracellular Mtb through lytic and antimicrobial properties only found in autolysosomes. Additionally, it has been demonstrated that standard anti-tuberculosis chemotherapy depends on host autophagy to coordinate successful antimicrobial responses to mycobacteria. Notably, autophagy constitutes an anti-inflammatory mechanism that protects against endomembrane damage triggered by several endogenous components or infectious agents and precludes excessive inflammation. It has also been reported that autophagy can be modulated by cytokines and other immunological signals. Most of the studies on autophagy as a defense mechanism against Mycobacterium have been performed using murine models or human cell lines. However, very limited information exists about the autophagic response in cells from tuberculosis patients. Herein, we review studies that face the autophagy process in tuberculosis patients as a component of the immune response of the human host against an intracellular microorganism such as Mtb. Interestingly, these findings might contribute to recognize new targets for the development of novel therapeutic tools to combat Mtb. Actually, either as a potential successful vaccine or a complementary immunotherapy, efforts are needed to further elucidate the role of autophagy during the immune response of the human host, which will allow to achieve protective and therapeutic benefits in human tuberculosis.
An Open-Source Whole Slide Image Registration Workflow at Cellular Precision Using Fiji, QuPath and Elastix
Authors: Chiaruttini Nicolas , Burri Olivier , Haub Peter , Guiet Romain , Sordet-Dessimoz Jessica , Seitz Arne
Published: January 2022

Image analysis workflows for Histology increasingly require the correlation and combination of measurements across several whole slide images. Indeed, for multiplexing, as well as multimodal imaging, it is indispensable that the same sample is imaged multiple times, either through various systems for multimodal imaging, or using the same system but throughout rounds of sample manipulation (e.g. multiple staining sessions). In both cases slight deformations from one image to another are unavoidable, leading to an imperfect superimposition Redundant and thus a loss of accuracy making it difficult to link measurements, in particular at the cellular level. Using pre-existing software components and developing missing ones, we propose a user-friendly workflow which facilitates the nonlinear registration of whole slide images in order to reach sub-cellular resolution level. The set of whole slide images to register and analyze is at first defined as a QuPath project. Fiji is then used to open the QuPath project and perform the registrations. Each registration is automated by using an elastix backend, or semi-automated by using BigWarp in order to interactively correct the results of the automated registration. These transformations can then be retrieved in QuPath to transfer any regions of interest from an image to the corresponding registered images. In addition, the transformations can be applied in QuPath to produce on-the-fly transformed images that can be displayed on top of the reference image. Thus, relevant data can be combined and analyzed throughout all registered slides, facilitating the analysis of correlative results for multiplexed and multimodal imaging.
Network-Based Approach and IVI Methodologies, a Combined Data Investigation Identified Probable Key Genes in Cardiovascular Disease and Chronic Kidney Disease
Authors: Ahmed Mohd Murshad , Tazyeen Safia , Haque Shafiul , Alsulimani Ahmad , Ali Rafat , Sajad Mohd , Alam Aftab , Ali Shahnawaz , Bagabir Hala Abubaker , Bagabir Rania Abubaker , Ishrat Romana
Published: January 2022

In fact, the risk of dying from CVD is significant when compared to the risk of developing end-stage renal disease (ESRD). Moreover, patients with severe CKD are often excluded from randomized controlled trials, making evidence-based therapy of comorbidities like CVD complicated. Thus, the goal of this study was to use an integrated bioinformatics approach to not only uncover Differentially Expressed Genes (DEGs), their associated functions, and pathways but also give a glimpse of how these two conditions are related at the molecular level. We started with GEO2R/R program (version 3.6.3, 64 bit) to get DEGs by comparing gene expression microarray data from CVD and CKD. Thereafter, the online STRING version 11.1 program was used to look for any correlations between all these common and/or overlapping DEGs, and the results were visualized using Cytoscape (version 3.8.0). Further, we used MCODE, a cytoscape plugin, and identified a total of 15 modules/clusters of the primary network. Interestingly, 10 of these modules contained our genes of interest (key genes). Out of these 10 modules that consist of 19 key genes (11 downregulated and 8 up-regulated), Module 1 (RPL13, RPLP0, RPS24, and RPS2) and module 5 (MYC, COX7B, and SOCS3) had the highest number of these genes. Then we used ClueGO to add a layer of GO terms with pathways to get a functionally ordered network. Finally, to identify the most influential nodes, we employed a novel technique called Integrated Value of Influence (IVI) by combining the network's most critical topological attributes. This method suggests that the nodes with many connections (calculated by hubness score) and high spreading potential (the spreader nodes are intended to have the most impact on the information flow in the network) are the most influential or essential nodes in a network. Thus, based on IVI values, hubness score, and spreading score, top 20 nodes were extracted, in which RPS27A non-seed gene and RPS2, a seed gene, came out to be the important node in the network.
Frequent Constriction-Like Echocardiographic Findings in Elite Athletes Following Mild COVID-19: A Propensity Score-Matched Analysis
Authors: Lakatos Bálint Károly , Tokodi Márton , Fábián Alexandra , Ladányi Zsuzsanna , Vágó Hajnalka , Szabó Liliána , Sydó Nóra , Csulak Emese , Kiss Orsolya , Babity Máté , Kiss Anna Réka , Gregor Zsófia , Szűcs Andrea , Merkely Béla , Kovács Attila
Published: January 2022

Background: The cardiovascular effects of SARS-CoV-2 in elite athletes are still a matter of debate. Accordingly, we sought to perform a comprehensive echocardiographic characterization of post-COVID athletes by comparing them to a non-COVID athlete cohort.

Methods: 107 elite athletes with COVID-19 were prospectively enrolled (P-CA; 23 ± 6 years, 23% female) 107 healthy athletes were selected as a control group using propensity score matching (N-CA). All athletes underwent 2D and 3D echocardiography. Left (LV) and right ventricular (RV) end-diastolic volumes (EDVi) and ejection fractions (EF) were quantified. To characterize LV longitudinal deformation, 2D global longitudinal strain (GLS) and the ratio of free wall vs. septal longitudinal strain (FWLS/SLS) were also measured. To describe septal flattening (SF—frequently seen in P-CA), LV eccentricity index (EI) was calculated.

Results: P-CA and N-CA athletes had comparable LV and RVEDVi (P-CA vs. N-CA; 77 ± 12 vs. 78 ± 13mL/m2; 79 ± 16 vs. 80 ± 14mL/m2). P-CA had significantly higher LVEF (58 ± 4 vs. 56 ± 4%, p < 0.001), while LVGLS values did not differ between P-CA and N-CA (−19.0 ± 1.9 vs. −18.8 ± 2.2%). EI was significantly higher in P-CA (1.13 ± 0.16 vs. 1.01 ± 0.05, p < 0.001), which was attributable to a distinct subgroup of P-CA with a prominent SF (n = 35, 33%), further provoked by inspiration. In this subgroup, the EI was markedly higher compared to the rest of the P-CA (1.29 ± 0.15 vs. 1.04 ± 0.08, p < 0.001), LVEDVi was also significantly higher (80 ± 14 vs. 75 ± 11 mL/m2, p < 0.001), while RVEDVi did not differ (82 ± 16 vs. 78 ± 15mL/m2). Moreover, the FWLS/SLS ratio was significantly lower in the SF subgroup (91.7 ± 8.6 vs. 97.3 ± 8.2, p < 0.01). P-CA with SF experienced symptoms less frequently (1.4 ± 1.3 vs. 2.1 ± 1.5 symptom during the infection, p = 0.01).

Conclusions: Elite athletes following COVID-19 showed distinct morphological and functional cardiac changes compared to a propensity score-matched control athlete group. These results are mainly driven by a subgroup, which presented with some echocardiographic features characteristic of constrictive pericarditis.