bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistin-Like Molecule α Dysregulates Cardiac Bioenergetics in Neonatal Rat Cardiomyocytes
Authors: Tao Bingdong , Kumar Santosh , Gomez-Arroyo Jose , Fan Chunling , Zhang Ailan , Skinner John , Hunter Elizabeth , Yamaji-Kegan Kazuyo , Samad Idris , Hillel Alexander T. , Lin Qing , Zhai Wenqian , Gao Wei Dong , Johns Roger A.
Published: April 2021

Heart (right) failure is the most frequent cause of death in patients with pulmonary arterial hypertension. Although historically, increased right ventricular afterload has been considered the main contributor to right heart failure in such patients, recent evidence has suggested a potential role of load-independent factors. Here, we tested the hypothesis that resistin–like molecule α (RELMα), which has been implicated in the pathogenesis of vascular remodeling in pulmonary artery hypertension, also contributes to cardiac metabolic remodeling, leading to heart failure. Recombinant RELMα (rRELMα) was generated via a Tet-On expression system in the T-REx 293 cell line. Cultured neonatal rat cardiomyocytes were treated with purified rRELMα for 24 h at a dose of 50 nM. Treated cardiomyocytes exhibited decreased mRNA and protein expression of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and transcription factors PPARα and ERRα, which regulate mitochondrial fatty acid metabolism, whereas genes that encode for glycolysis-related proteins were significantly upregulated. Cardiomyocytes treated with rRELMα also exhibited a decreased basal respiration, maximal respiration, spare respiratory capacity, ATP-linked OCR, and increased glycolysis, as assessed with a microplate-based cellular respirometry apparatus. Transmission electron microscopy revealed abnormal mitochondrial ultrastructure in cardiomyocytes treated with rRELMα. Our data indicate that RELMα affects cardiac energy metabolism and mitochondrial structure, biogenesis, and function by downregulating the expression of the PGC-1α/PPARα/ERRα axis.
Profiling of miR-205/P4HA3 Following Angiotensin II-Induced Atrial Fibrosis: Implications for Atrial Fibrillation
Authors: Xiao Zezhou , Reddy Desai Pavan Kumar , Xue Chuqing , Liu Ximao , Chen Xiong , Li Jiale , Ling Xiao , Zheng Shaoyi
Published: April 2021

Objective: Atrial fibroblasts are the main component of atrial fibrosis. Data in previous studies proved the implication of miRNAs in AF progression and the association of miR-205 with cancer associated-fibroblasts, while no evidence supported the implication of miR-205 in atrial fibrosis. Therefore, this study aims to explore the effect and mechanism of miR-205/P4HA3 axis on atrial fibrosis.

Methods: Angiotensin II (Ang II) was used to induce atrial fibrosis model in rats, which was verified by H&E staining and Masson staining. qRT-PCR and Western blot were applied to measure the expressions of miR-205, P4HA3, collagen I, and α-SMA. The rat atrial fibroblasts were isolated and then subjected to Ang II treatment or cell transfection for determination of cell biological functions using CCK-8, BrdU assay, TUNEL staining, and cell scratch assay. qRT-PCR and Western blot was applied to analyze the expressions of miR-205, P4HA3, collagen I, α-SMA, JNK, and p-JNK in atrial fibroblasts. Dual-luciferase reporter gene assay and RNA immune-precipitation experiment was employed to verify the binding relationship between miR-205 and P4HA3.

Results: Ang II induced rats had disordered arrangement of atrial muscles with uneven nuclear sizes and necrotic atrial myocytes, and increased collagen deposition, in which elevated expressions of P4HA3, collagen I, and α-SMA as well as suppressed expression level of miR-205 were found. In vitro, Ang II treatment in atrial fibroblasts with overexpression of P4HA3 facilitated cellular migration and proliferation, with the induction of JNK signaling pathway. However, these trends were reversed after transfection with miR-205 mimic. P4HA3 is a target gene of miR-205.

Conclusion: The miR-205/P4HA3 axis is implicated in atrial fibrosis by inhibition of rat fibroblast proliferation and migration and the inactivation of JNK signaling pathway.
Estimated Glomerular Filtration Rate Is Associated With an Increased Risk of Death in Heart Failure Patients With Preserved Ejection Fraction
Authors: Chen Zhuo , Lin Qian , Li Jingen , Wang Xinyi , Ju Jianqing , Xu Hao , Shi Dazhuo
Published: April 2021

Background: Renal dysfunction is associated with adverse cardiovascular outcomes in patients with heart failure (HF), but its impact on patients with heart failure with preserved ejection fraction (HFpEF) remains unclear.

Methods: 3,392 subjects of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial were assigned to two groups by estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 or 30–59 ml/min/1.73 m2. The outcomes, including all-cause death, cardiovascular death and HF hospitalization, were examined by multivariable cox models.

Results: Over a median follow-up of 3.4 ± 1.7 years, a total of 524 all-cause deaths, 334 cardiovascular deaths and 440 HF hospitalizations occurred. Compared with patients with eGFR ≥ 60 ml/min/1.73 m2, those with eGFR 30–59 ml/min/1.73 m2 were associated with an increased risk of the all-cause death [adjusted hazard ratio (HR), 1.47; 95% confidence interval (CI), 1.24–1.76; P < 0.001], cardiovascular death (adjusted HR, 1.53; 95% CI: 1.23–1.91; p < 0.001), and HF hospitalization (adjusted HR: 1.21; 95% CI: 1.00–1.47; p = 0.049) after multivariable adjustment for potential confounders.

Conclusions: eGFR 30–59 ml/min/1.73 m2 was related to an increased risk of all-cause death, cardiovascular death and HF hospitalization in HFpEF patients.
Applications of Engineering Techniques in Microvasculature Design
Authors: Al Halawani Aleen , Wang Ziyu , Liu Linyang , Zhang Miao , Weiss Anthony S.
Published: April 2021

Achieving successful microcirculation in tissue engineered constructs in vitro and in vivo remains a challenge. Engineered tissue must be vascularized in vitro for successful inosculation post-implantation to allow instantaneous perfusion. To achieve this, most engineering techniques rely on engineering channels or pores for guiding angiogenesis and capillary tube formation. However, the chosen materials should also exhibit properties resembling the native extracellular matrix (ECM) in providing mechanical and molecular cues for endothelial cells. This review addresses techniques that can be used in conjunction with matrix-mimicking materials to further advance microvasculature design. These include electrospinning, micropatterning and bioprinting. Other techniques implemented for vascularizing organoids are also considered for their potential to expand on these approaches.
Interleukin-17-Producing CD4+ T Cells Promote Inflammatory Response and Foster Disease Progression in Hyperlipidemic Patients and Atherosclerotic Mice
Authors: Wang Yin , Li Wenming , Zhao Tingrui , Zou Yao , Deng Tao , Yang Zhangyou , Yuan Zhiyi , Ma Limei , Yu Ruihong , Wang Tingting , Yu Chao
Published: April 2021

Atherosclerosis is a chronic inflammatory disease. Interleukin-17-producing CD4+ T cells (Th17 cells) play important roles in the progression of atherosclerosis. However, most of the studies were focused on the advanced stage of atherosclerosis. In the current study, we investigated the roles of Th17 cells, relevant mechanisms in hyperlipidemic patients, and different stages of atherosclerotic mice. Human blood samples were collected, and percentages of Th17 cells, macrophages, and neutrophils were analyzed by flow cytometry. ApoE−/− mice were fed with high-fat diet (HFD) and sacrificed at different time points to evaluate the infiltration of inflammatory cells at different stages of atherosclerosis. Furthermore, essential mechanisms of IL-17A in atherosclerotic inflammatory milieu formation were studied in vivo by intraperitoneal injection with monoclonal anti-murine IL-17 antibody. Our study reveals the higher percentages of Th17 cells, monocytes, and neutrophils in hyperlipidemic patients compared to healthy donors. Meanwhile, we also identify an infiltration of Th17 cells in the early stage of atherosclerosis (4 weeks after HFD), which maintains at high level until late stage of atherosclerosis (20 weeks after HFD). What is more, inflammatory cells including macrophages and neutrophils were also accumulated in atherosclerotic lesions. Neutralization of IL-17 in ApoE−/− mice resulted in less infiltration of macrophages and neutrophils and smaller atherosclerotic lesions. Importantly, in accordance with what is found in the mouse model, positive correlations between Th17 cells and macrophages or neutrophils were observed in hyperlipidemic patients. In conclusion, our clinical and mouse model data together reveal a pro-atherogenic role of Th17 cells through the promotion of inflammation in hyperlipidemic conditions and different stages of atherosclerosis, which further supports the notion that IL-17 may be a therapy target for the treatment of atherosclerosis.
Performance Analysis of Different Embedded Systems and Open-Source Optimization Packages Towards an Impulsive MPC Artificial Pancreas
Authors: Goez-Mora Jhon E. , Villa-Tamayo María F. , Vallejo Monica , Rivadeneira Pablo S.
Published: April 2021

Current technological advances have brought closer to reality the project of a safe, portable, and efficient artificial pancreas for people with type 1 diabetes (T1D). Among the developed control strategies for T1D, model predictive control (MPC) has been emphasized in literature as a promising control for glucose regulation. However, these control strategies are commonly designed in a computer environment, regardless of the limitations of a portable device. In this paper, the performances of six embedded platforms and three open-source optimization solver algorithms are assessed for T1D treatment. Their advantages and limitations are clarified using four MPC formulations of increasing complexity and a hardware-in-the-loop methodology to evaluate glucose control in virtual adult subjects. The performance comparison includes the execution time, the difference concerning the evolution obtained in MATLAB, the processor temperature, energy consumption, time percentage in normoglycemia, and the number of hypo- and hyperglycemic events. Results show that Quadprog is the package that faithfully follows the results obtained with control strategies designed and tuned on a computer with the MATLAB software. In addition, the Raspberry Pi 3 and the Tinker Board S embedded systems present the appropriate characteristics to be implemented as portable devices in the artificial pancreas application according to the criteria set out in this work.
Cytotoxic Effect of Progesterone, Tamoxifen and Their Combination in Experimental Cell Models of Human Adrenocortical Cancer
Authors: Rossini Elisa , Tamburello Mariangela , Abate Andrea , Beretta Silvia , Fragni Martina , Cominelli Manuela , Cosentini Deborah , Hantel Constanze , Bono Federica , Grisanti Salvatore , Poliani Pietro Luigi , Tiberio Guido A. M. , Memo Maurizio , Sigala Sandra , Berruti Alfredo
Published: April 2021

Progesterone (Pg) and estrogen (E) receptors (PgRs and ERs) are expressed in normal and neoplastic adrenal cortex, but their role is not fully understood. In literature, Pg demonstrated cytotoxic activity on AdrenoCortical Carcinoma (ACC) cells, while tamoxifen is cytotoxic in NCI-H295R cells. Here, we demonstrated that in ACC cell models, ERs were expressed in NCI-H295R cells with a prevalence of ER-β over the ER-α.Metastasis-derived MUC-1 and ACC115m cells displayed a very weak ER-α/β signal, while PgR cells were expressed, although at low level. Accordingly, these latter were resistant to the SERM tamoxifen and scarcely sensitive to Pg, as we observed a lower potency compared to NCI-H295R cells in cytotoxicity (IC50: MUC-1 cells: 67.58 µM (95%CI: 63.22–73.04), ACC115m cells: 51.76 µM (95%CI: 46.45–57.67) and cell proliferation rate. Exposure of NCI-H295R cells to tamoxifen induced cytotoxicity (IC50: 5.43 µM (95%CI: 5.18–5.69 µM) mainly involving ER-β, as their nuclear localization increased after tamoxifen: Δ A.U. treated vs untreated: 12 h: +27.04% (p < 0.01); 24 h: +36.46% (p < 0.0001). This effect involved the SF-1 protein reduction: Pg: −36.34 ± 9.26%; tamoxifen: −46.25 ± 15.68% (p < 0.01). Finally, in a cohort of 36 ACC samples, immunohistochemistry showed undetectable/low level of ERs, while PgR demonstrated a higher expression. In conclusion, ACC experimental cell models expressed PgR and low levels of ER in line with data obtained in patient tissues, thus limiting the possibility of a clinical approach targeting ER. Interestingly, Pg exerted cytotoxicity also in metastatic ACC cells, although with low potency.
Noise-Related Song Variation Affects Communication: Bananaquits Adjust Vocally to Playback of Elaborate or Simple Songs
Authors: Winandy Gabrielle S. M. , Japyassú Hilton F. , Izar Patrícia , Slabbekoorn Hans
Published: April 2021

Birds communicate through acoustic variation in their songs for territorial defense and mate attraction. Noisy urban conditions often induce vocal changes that can alleviate masking problems, but that may also affect signal value. We investigated this potential for a functional compromise in a neotropical songbird: the bananaquit (Coereba flaveola). This species occurs in urban environments with variable traffic noise levels and was previously found to reduce song elaboration in concert with a noise-dependent reduction in song frequency bandwidth. Singing higher and in a narrower bandwidth may make their songs more audible in noisy conditions of low-frequency traffic. However, it was unknown whether the associated decrease in syllable diversity affected their communication. Here we show that bananaquits responded differently to experimental playback of elaborate vs. simple songs. The variation in syllable diversity did not affect general response strength, but the tested birds gave acoustically distinct song replies. Songs had fewer syllables and were lower in frequency and of wider bandwidth when individuals responded to elaborate songs compared to simple songs. This result suggests that noise-dependent vocal restrictions may change the signal value of songs and compromise their communicative function. It remains to be investigated whether there are consequences for individual fitness and how such effects may alter the diversity and density of the avian community in noisy cities.
Plant Mediated Interactions: Lower Sawfly Survival on Pines Previously Browsed by Moose
Authors: Nordkvist Michelle , Björkman Christer , Klapwijk Maartje J.
Published: April 2021

Insect herbivore performance and arthropod communities can be affected by mammalian grazing and browsing via altered plant communities and vegetation structure. Far less is known about whether changes to plant architecture can cause similar effects. Browsing generated changes to within plant architecture could potentially have large consequences for arthropod communities, herbivore survival and eventually damage to plants. This study investigates plant-mediated effects of ungulate browsing on arthropod predator communities and on the survival of herbivorous insects. More specifically we studied how different levels of ungulate browsing (1) influenced the arthropod predator community on Scots pine (Pinus sylvestris) and (2) affected the survival of the European pine sawfly (Neodiprion sertifer). We related these response variables to browsing-inflicted changes in pine architecture. An observational study of generalist arthropod predators on pine trees revealed a trend toward a quadratic response of ants to browsing intensity—i.e., a higher abundance of ants on moderately browsed trees and lower abundance on intensively browsed trees. A field survey of sawfly larvae revealed a 19% lower larval survival on browsed compared to un-browsed pines, but no difference in survival comparing pines with moderate and high intensity of browsing. A structural equation model revealed that moose generated changes to pine architecture had only a small effect on sawfly larval survival, suggesting additional mediating pine traits affected by browsing. We conclude that insect survival can be altered by ungulate browsing, which could affect damage levels.
Indigenous Knowledge and Forest Succession Management in the Brazilian Amazon: Contributions to Reforestation of Degraded Areas
Authors: Schmidt Marcus Vinícius C. , Ikpeng Yakuna Ullillo , Kayabi Tariaiup , Sanches Rosely Alvim , Ono Katia Yukari , Adams Cristina
Published: April 2021

The indigenous systems of agricultural and forest management in the Amazon are characterized by a deep knowledge of ecological processes, biodiversity, and the use and management of fire. The influence of these systems on the distribution of biodiversity includes semi-domesticated and domesticated species and landscapes, which have led to extensive anthropogenic or cultural forests. However, in many places, the livelihoods of indigenous peoples are being transformed by the intensification of agriculture and social, ecological, and economic changes, putting at risk the sustainability of production systems and food security and sovereignty of these peoples. In the last years, in the Xingu Indigenous Territory (XIT), the food production systems and the form of occupation of territories have changed, affecting the recovery of secondary forests, which now demand a too long period. The increase in the number and frequency of fires has aggravated this situation, due to a drier climate that has become predominant in the region. Changes in climate are attributed to deforestation in the neighboring municipalities, especially in the headwaters of the Xingu river basin. This study was conducted among the Kawaiwete (Tupi-Guarani) and the Ikpeng (Carib-Arara) peoples in the XIT, in the state of Mato Grosso, Brazil. The main objective was to develop alternative techniques of forest management based on indigenous and scientific knowledge more adapted to the new livelihood contexts, aiming to favor forest regeneration in areas dominated by shifting cultivation. We sought to answer the following questions: (I) How do forests regenerate during the fallow period? (II) How can local management improve forest regeneration? (III) Are there indicator species for secondary succession, soil recovery, and vulnerability to fires? (IV) Is the increase in the number of fires affecting the sustainability of the shifting cultivation systems? Our results show that some local practices based on indigenous knowledge have the potential to facilitate natural regeneration, such as choosing forest areas that have been recovered for agricultural use, limiting the number of cultivation cycles, protecting and selecting of individual trees during cultivation period, and attracting seed dispersers. Assisted natural regeneration strategies grounded on indigenous knowledge are promising ways to restore degraded lands of the XIT.
Design, Dimerization, and Recombinant Production of MCh-AMP1–Derived Peptide in Escherichia coli and Evaluation of Its Antifungal Activity and Cytotoxicity
Authors: Seyedjavadi Sima Sadat , Khani Soghra , Amani Jafar , Halabian Raheleh , Goudarzi Mehdi , Hosseini Hamideh Mahmoodzadeh , Eslamifar Ali , Shams-Ghahfarokhi Masoomeh , Imani Fooladi Abbas Ali , Razzaghi-Abyaneh Mehdi
Published: April 2021

Fungal species resistant to current antifungal agents are considered as a serious threat to human health, the dilemma that has dragged attentions toward other sources of antifungals such as antimicrobial peptides (AMPs). In order to improve biological activity of a recently described antifungal peptide MCh-AMP1 from Matricaria chamomilla flowers, MCh-AMP1dimer (DiMCh-AMP1), containing 61 amino acid residues connected by flexible linker (GPDGSGPDESGPDES), was designed and expressed in Escherichia coli, and its structure was analyzed using bioinformatics tools. DiMCh-AMP1 synthetic gene was cloned into pET-28a expression vector, which was then used to transform E. coli BL21 (DE3) strain. His-tag purification was achieved using metal-chelate affinity chromatography. Because there is no methionine residue in the DiMCh-AMP1 sequence, cyanogen bromide was successfully used to separate the target product from the tag. Reverse-phase high-performance liquid chromatography was used as the final step of purification. Results showed that recombinant peptide was produced in considerable amounts (0.9 mg/L) with improved antifungal activity toward both yeasts and molds compared to its monomeric counterpart. The minimum inhibition concentration and minimum fungicidal concentration values of DiMCh-AMP1 against Candida and Aspergillus species were reported in the range of 1.67–6.66 μM and 3.33–26.64 μM, respectively. Our results showed that while antifungal activity of dimerized peptide was improved considerably, its cytotoxicity was decreased, implying that DiMCh-AMP1 could be a potential candidate to design an effective antifungal agent against pathogenic yeasts and molds.
A Survey on Operation Concept, Advancements, and Challenging Issues of Urban Air Traffic Management
Authors: Shrestha Rakesh , Oh Inseon , Kim Shiho
Published: April 2021

The recent growth and adoption of unmanned aerial vehicles (UAVs) is due to their low development cost, high aerial mobility, advanced battery technology, rotors, gyroscopes, GPS, cameras, sensors, and wide range of applications. The UAV offers new possibilities for business in civil and noncivil applications such as parcel delivery, aerial mapping, agriculture, wildlife conservation, surveillance, and search and rescue. However, considering the exponential growth of various types of aerial vehicles, it is clear that advanced air traffic management services are urgently needed to control and handle the ever-increasing air traffics. In this paper, we first present the two major low-altitude UAV traffic management systems in the United States and Europe and compare them thoroughly. We present the global vision and advancement of UAV traffic management system. To understand the complexity of future air transportation system, we discuss the necessary elements required for an urban air traffic management system. We provide key strategic elements for an advanced urban traffic management through connectivity, open source, safety enhancement, and automation to maximize its impacts on the innovative future air traffic and mobility system. In the end, we discuss the challenging security issues in urban traffic management system.
A Quest for a Universal Plasma-Derived Antivenom Against All Elapid Neurotoxic Snake Venoms
Authors: Ratanabanangkoon Kavi
Published: April 2021

This review describes the research aimed at the development of universal antivenom against elapid neurotoxic snake venoms. The antivenoms produced in Thailand in the 1980s were of low potency, especially against the elapid venoms. This was thought to be due to the low immunogenicity of the α-neurotoxins, which are the most lethal toxins in these venoms. Comparisons of various α-neurotoxin conjugates and polymers, and also different immunological adjuvants, showed that the adjuvant used is the major determinant in the antibody response in horses. The potent Freund’s adjuvant was not used due to its severe local side-effect in horses. Therefore, a novel immunization protocol termed ‘low dose, low volume multi-site’ was developed for use in horses. This immunization protocol has led to the production of highly potent monospecific antivenoms against several elapid and viperid venoms, and two potent polyspecific antivenoms, one against 4 neurotoxic and another against 3 hematotoxic venoms. The immunization protocol has also led to other improvements in antivenom production including: several fold increases in antiserum potency, a reduction in the time required to reach therapeutically useful antibody titers, a 90% reduction in the amount of venom used, and 100% of the horses responding to the immunization program. This development is partly responsible for significant decrease in the Thailand’s annual snakebite death toll from a few dozens to mostly nil in recent years. Finally, a simple and novel immunization strategy, using a ‘diverse toxin repertoire’ composed of numerous elapid toxin fractions as immunogen, was proposed and tested. This immunization procedure has resulted in the successful production of a widely paraspecific antiserum against at least 36 neurotoxic venoms of 28 species encompassing 10 genera and from 20 countries on four continents, and possibly against all elapid venoms with α-neurotoxins as the lethal toxins. These results indicate that, with optimizations of the composition of the ‘diverse toxin repertoire’, the immunization scheme and antibody fractionation to increase the antivenom neutralizing potency, an effective universal antivenom against the neurotoxic elapid snakes of the world can be produced.
Case Report: Novel Compound Heterozygous RNASEH2B Mutations Cause Aicardi–Goutières Syndrome
Authors: Garau Jessica , Masnada Silvia , Dragoni Francesca , Sproviero Daisy , Fogolari Federico , Gagliardi Stella , Izzo Giana , Varesio Costanza , Orcesi Simona , Veggiotti Pierangelo , Zuccotti Gian Vincenzo , Pansarasa Orietta , Tonduti Davide , Cereda Cristina
Published: April 2021

Aicardi–Goutières Syndrome (AGS) is a rare disorder characterized by neurological and immunological signs. In this study we have described a child with a phenotype consistent with AGS carrying a novel compound heterozygous mutation in RNASEH2B gene. Next Generation Sequencing revealed two heterozygous variants in RNASEH2B gene. We also highlighted a reduction of RNase H2B transcript and protein levels in all the family members. Lower protein levels of RNase H2A have been observed in all the members of the family as well, whereas a deep depletion of RNase H2C has only been identified in the affected child. The structural analysis showed that both mutations remove many intramolecular contacts, possibly introducing conformational rearrangements with a decrease of the stability of RNase H2B and strongly destabilizing the RNase H2 complex. Taken together, these results highlight the importance of an integrated diagnostic approach which takes into consideration clinical, genetic, and molecular analyses.
Fine Scale Temporal and Spatial Dynamics of the Stony Coral Tissue Loss Disease Outbreak Within the Lower Florida Keys
Authors: Williams Sara D. , Walter Cory S. , Muller Erinn M.
Published: April 2021

One of the latest threats to Florida’s Coral Reef is the stony coral tissue loss disease (SCTLD) outbreak which affects all but a few Caribbean scleractinian species and has spread throughout the Caribbean since 2014. Without a known pathogen, ecological studies of disease dynamics are essential for understanding SCTLD susceptibility at the individual colony and reef level. We investigated the epizootiology of the SCTLD outbreak in the lower Florida Keys at two spatial scales (among reefs ∼1 km and within reefs <10 m) over a 19 month period. In May 2018, three sites absent of SCTLD were established to characterize coral demographics (i.e., live tissue cover and colony diameter) along an offshore to nearshore gradient, and were subsequently surveyed for disease every 2–3 weeks until December 2019. SCTLD was first noted within the offshore and mid-channel reef sites in early October 2018 and later appeared at the nearshore site in early February 2019. SCTLD was negatively correlated with thermal stress, showing reduced progression and incidence rates after 2–3 weeks of water temperatures above the mean monthly maximum temperature for the region (i.e., 2–3 degree heating weeks). Although Pseudodiploria strigosa, Dichocoenia stokesii, Colpophyllia natans, and Diploria labyrinthiformis were the most susceptible species at our sites, areas with more Montastraea cavernosa and Orbicella faveolata colonies had higher prevalence and greater tissue loss associated with disease. The disease was more severe within quadrats with high species diversity, high coral cover, and disproportionately affected larger colonies. Our spatial analyses suggest that (1) SCTLD followed a contagious disease model within small (<10 m) spatial scales, (2) colonies within 1.5–3 m of a diseased coral were at higher risk for subsequently showing disease signs compared with those farther away, and (3) high incidence rates coincided with the loss of small scale (<10 m radius) spatial clustering, suggesting pulses of contagious spread on large spatial scales.
Characteristics of Fundal Changes in Fundus Tessellation in Young Adults
Authors: Lyu Hanyi , Chen Qiuying , Hu Guangyi , Shi Ya , Ye Luyao , Yin Yao , Fan Ying , Zou Haidong , He Jiangnan , Zhu Jianfeng , Xu Xun
Published: April 2021

Purpose: To explore the characteristics and associated factors of fundus tessellation, especially the alternation of choroidal thickness among different degrees of tessellated fundus in young adults.

Design: Cross-sectional, population-based study.

Methods: A total of 796 students were included in the study and underwent comprehensive ophthalmic examinations, including anterior segment examinations and swept-source optical coherence tomography (OCT) measurements. The degree of tessellated fundus was assessed by fundus photographs applying an early treatment of diabetic retinopathy study grid to evaluate the location of fundus tessellation and then divided into five groups. The topographic variation and factors, tilted disc ratio, parapapillary atrophy (PPA), retinal thickness (ReT), choroidal thickness (ChT), and subfoveal scleral thickness (SST) related to tessellated fundus were analyzed.

Results: Compared to normal fundus, tessellated fundus had a lower spherical equivalent (SE) (p < 0.0001), worse best-corrected visual acuity (BCVA)(p = 0.043), longer axial length (AL) (p < 0.0001), thinner retina (p < 0.0001), thinner (p < 0.0001) choroid, and thinner sclera in center fovea (p = 0.0035). Among all subfields of macular and peripapillary regions, center fovea and macula-papillary region showed the most significant decrease in choroidal thickness. The proportion of fundus tessellation significantly increased with lower body weight index (BMI) (p = 0.0067), longer AL (p < 0.0001), larger PPA(p = 0.0058), thinner choroid (p < 0.0001), and thinner sclera (p < 0.0001).

Conclusions: Eyes showed more severe myopic morphological alternation with the increasement of proportion of fundus tessellation to the center fovea, including a significant decrease in both choroid and scleral thickness. Choroidal thinning may progress most rapidly in the macula-papillary region as fundus tessellation approaches to the center fovea.
Emergomycosis, an Emerging Systemic Mycosis in Immunocompromised Patients: Current Trends and Future Prospects
Authors: Samaddar Arghadip , Sharma Anuradha
Published: April 2021

Recently, the global emergence of emergomycosis, a systemic fungal infection caused by a novel dimorphic fungus Emergomyces species has been observed among immunocompromised individuals. Though initially classified under the genus Emmonsia, a taxonomic revision in 2017 based on DNA sequence analyses placed five Emmonsia-like fungi under a separate genus Emergomyces. These include Emergomyces pasteurianus, Emergomyces africanus, Emergomyces canadensis, Emergomyces orientalis, and Emergomyces europaeus. Emmonsia parva was renamed as Blastomyces parvus, while Emmonsia crescens and Emmonsia sola remained within the genus Emmonsia until a taxonomic revision in 2020 placed both the species under the genus Emergomyces. However, unlike other members of the genus, Emergomyces crescens and Emergomyces sola do not cause disseminated disease. The former causes adiaspiromycosis, a granulomatous pulmonary disease, while the latter has not been associated with human disease. So far, emergomycosis has been mapped across four continents: Asia, Europe, Africa and North America. However, considering the increasing prevalence of HIV/AIDS, it is presumed that the disease must have a worldwide distribution with many cases going undetected. Diagnosis of emergomycosis remains challenging. It should be considered in the differential diagnosis of histoplasmosis as there is considerable clinical and histopathological overlap between the two entities. Sequencing the internal transcribed spacer region of ribosomal DNA is considered as the gold standard for identification, but its application is compromised in resource limited settings. Serological tests are non-specific and demonstrate cross-reactivity with Histoplasma galactomannan antigen. Therefore, an affordable, accessible, and reliable diagnostic test is the need of the hour to enable its diagnosis in endemic regions and also for epidemiological surveillance. Currently, there are no consensus guidelines for the treatment of emergomycosis. The recommended regimen consists of amphotericin B (deoxycholate or liposomal formulation) for 1–2 weeks, followed by oral itraconazole for at least 12 months. This review elaborates the taxonomic, clinical, diagnostic, and therapeutic aspects of emergomycosis. It also enumerates several novel antifungal drugs which might hold promise in the treatment of this condition and therefore, can be potential areas of future studies.
Recent Trends on Biosurfactants With Antimicrobial Activity Produced by Bacteria Associated With Human Health: Different Perspectives on Their Properties, Challenges, and Potential Applications
Authors: De Giani Alessandra , Zampolli Jessica , Di Gennaro Patrizia
Published: April 2021

The attention towards the bacteria associated with human health is growing more and more, above all regarding the bacteria that inhabit the niches offered by the human body, i.e., the gastrointestinal tract, skin, vaginal environment, and lungs. Among the secondary metabolites released by microorganisms associated with human health, little consideration is given to the biosurfactants, molecules with both hydrophobic and hydrophilic nature. Their role in the complex human environment is not only the mere biosurfactant function, but they could also control the microbiota through the quorum sensing system and the antimicrobial activity. These functions protect them and, accordingly, the human body principally from microbial and fungal pathogens. Consequently, nowadays, biosurfactants are emerging as promising bioactive molecules due to their very different structures, biological functions, low toxicity, higher biodegradability, and versatility. Therefore, this review provides a comprehensive perspective of biosurfactants with antimicrobial activity produced by bacteria associated with the human body and related to everything human beings are in contact with, e.g., food, beverages, and food-waste dumping sites. For the first time, the role of an “-omic” approach is highlighted to predict gene products for biosurfactant production, and an overview of the available gene sequences is reported. Besides, antimicrobial biosurfactants’ features, challenges, and potential applications in the biomedical, food, and nutraceutical industries are discussed.
Prevalence and Relatedness of mcr-1-Mediated Colistin-Resistant Escherichia coli Isolated From Livestock and Farmers in Japan
Authors: Nakano Akiyo , Nakano Ryuichi , Nishisouzu Ryuji , Suzuki Yuki , Horiuchi Saori , Kikuchi-Ueda Takane , Ubagai Tsuneyuki , Ono Yasuo , Yano Hisakazu
Published: April 2021

Colistin is used to treat infectious diseases in humans and livestock; it has also been used as a feed additive for livestock for approximately 50 years. Since the mcr-1 plasmid-mediated colistin resistance gene was discovered in China in 2015, it has been detected worldwide, mainly in livestock. In this study, we investigated the prevalence and characteristics of mcr-mediated colistin-resistant Escherichia coli in livestock and farmers in Japan. We collected fecal samples from 295 healthy livestock (202 cattle and 93 swine) and 62 healthy farmers from 72 livestock farms (58 cattle farms and 14 swine farms) between 2013 and 2015. Twenty-eight mcr-1-harboring E. coli strains were isolated from 25 livestock (six cattle and 19 swine) and three farmers (two cattle farmers and one swine farmer). The prevalence rates of mcr-1-harboring E. coli in livestock and farmers were 8.47 and 4.84%, respectively. Of the 28 strains, the resistance genes of three were transferable via the mcr-1-coding plasmids to E. coli J53 at low frequencies (10−7–10−8). Six strains coharbored mcr-1 with CTX-M β-lactamases (CTX-M-14, CTX-M-27, or CTX-M-156). Of the isolates obtained from livestock and farmers in four farms (farms C, I, N, and P), nine strains had the same genotypical characteristics (sequence types and pulsed-field gel electrophoresis band patterns), plasmid characteristics (incompatibility group and plasmid transferability), and minimum inhibitory concentrations. Thus, the findings suggested that clonal strains could spread among livestock and farmers within farms. To our knowledge, this is the first study to detect clonal relatedness of mcr-1-mediated colistin-resistant E. coli in livestock and farmers. It is suggested that farmers are at a higher risk of acquiring mcr-1-harboring strains, calling for our attention based on the One Health concept.
Development of TACE Refractoriness Scores in Hepatocellular Carcinoma
Authors: Chen Li , Yu Chen-Xi , Zhong Bin-Yan , Zhu Hai-Dong , Jin Zhi-Cheng , Zhu Guang-Yu , Zhang Qi , Ni Cai-Fang , Teng Gao-Jun
Published: April 2021

Purpose: To identify the independent risk factors for transarterial embolization (TACE) refractoriness and to develop a novel TACE refractoriness score and nomogram for predicting TACE refractoriness in patients with hepatocellular carcinoma (HCC).

Methods: Between March 2006 and March 2016, HCC patients who underwent TACE monotherapy as initial treatment at two hospitals formed the study cohort and validation cohort. The criteria of TACE refractoriness followed the Japan Society of Hepatology 2014 version of TACE refractoriness. In the study cohort, the independent risk factors for TACE refractoriness were identified, and TACE refractoriness score and nomogram were then developed. The accuracy of the systems was validated externally in the validation cohort.

Results: In total, 113 patients from hospital A formed the study cohort and 122 patients from hospital B formed the validation cohort. In the study cohort, 82.3% of the patients (n = 93) developed TACE refractoriness with a median overall survival (OS) of 540 days (95% CI, 400.8–679.1), and the remaining 20 patients in the TACE-non-refractory group had a median OS of 1,257 days (95% CI, 338.8–2,175.2) (p = 0.019). The median time for developing TACE refractoriness was 207 days (95% CI, 134.8–279.2), and a median number of two TACE procedures were performed after refractoriness developed. The independent risk factors for TACE refractoriness were the number of tumors and bilobular invasion of HCC. TACE refractoriness scores <3.5 indicated a lower incidence of TACE refractoriness, whereas scores >3.5 points indicated a higher incidence (p < 0.001). In the validation cohort, 77.9% of the patients (n = 95) developed TACE refractoriness with a median OS of 568 days (95% CI, 416.3–719.7), and a median OS of 1,324 days was observed in the TACE-non-refractory group (n = 27; 95% CI, 183.5–2,464.5).

Conclusions: TACE refractoriness impairs the OS of HCC patients. The number of tumors and bilobular invasion status were independent risk factors for TACE refractoriness. The TACE refractoriness score can be an effective tool and easy approach to predict the risk of TACE refractoriness status.
Regulation of Dynamic Protein S-Acylation
Authors: Chen Jessica J. , Fan Ying , Boehning Darren
Published: April 2021

Protein S-acylation is the reversible addition of fatty acids to the cysteine residues of target proteins. It regulates multiple aspects of protein function, including the localization to membranes, intracellular trafficking, protein interactions, protein stability, and protein conformation. This process is regulated by palmitoyl acyltransferases that have the conserved amino acid sequence DHHC at their active site. Although they have conserved catalytic cores, DHHC enzymes vary in their protein substrate selection, lipid substrate preference, and regulatory mechanisms. Alterations in DHHC enzyme function are associated with many human diseases, including cancers and neurological conditions. The removal of fatty acids from acylated cysteine residues is catalyzed by acyl protein thioesterases. Notably, S-acylation is now known to be a highly dynamic process, and plays crucial roles in signaling transduction in various cell types. In this review, we will explore the recent findings on protein S-acylation, the enzymatic regulation of this process, and discuss examples of dynamic S-acylation.
Macrophages Inhibit Ciliary Protein Levels by Secreting BMP-2 Leading to Airway Epithelial Remodeling Under Cigarette Smoke Exposure
Authors: Wang Zhigang , Liang Wenzhang , Ma Cuiqing , Wang Jiachao , Gao Xue , Wei Lin
Published: April 2021

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high morbidity and mortality worldwide. So far, smoking is still its leading cause. The characteristics of COPD are emphysema and airway remodeling, as well as chronic inflammation, which were predominated by macrophages. Some studies have reported that macrophages were involved in emphysema and chronic inflammation, but whether there is a link between airway remodeling and macrophages remains unclear. In this study, we found that both acute and chronic cigarette smoke exposure led to an increase of macrophages in the lung and a decrease of ciliated cells in the airway epithelium of a mouse model. The results of in vitro experiments showed that the ciliary protein (β-tubulin-IV) levels of BEAS-2B cells could be inhibited when co-cultured with human macrophage line THP-1, and the inhibitory effect was augmented with the stimulation of cigarette smoke extract (CSE). Based on the results of transcriptome sequencing, we focused on the protein, bone morphogenetic protein-2 (BMP-2), secreted by the macrophage, which might mediate this inhibitory effect. Further studies confirmed that BMP-2 protein inhibited β-tubulin-IV protein levels of BEAS-2B cells under the stimulation of CSE. Coincidentally, this inhibitory effect could be nearly blocked by the BMP receptor inhibitor, LDN, or could be interfered with BMP-2 siRNA. This study suggests that activation and infiltration of macrophages in the lung induced by smoke exposure lead to a high expression of BMP-2, which in turn inhibits the ciliary protein levels of the bronchial epithelial cells, contributing to the remodeling of airway epithelium, and aggravates the development of COPD.
Biomaterials for Neural Tissue Engineering
Authors: Doblado Laura Rodríguez , Martínez-Ramos Cristina , Pradas Manuel Monleón
Published: April 2021

The therapy of neural nerve injuries that involve the disruption of axonal pathways or axonal tracts has taken a new dimension with the development of tissue engineering techniques. When peripheral nerve injury (PNI), spinal cord injury (SCI), traumatic brain injury (TBI), or neurodegenerative disease occur, the intricate architecture undergoes alterations leading to growth inhibition and loss of guidance through large distance. To improve the limitations of purely cell-based therapies, the neural tissue engineering philosophy has emerged. Efforts are being made to produce an ideal scaffold based on synthetic and natural polymers that match the exact biological and mechanical properties of the tissue. Furthermore, through combining several components (biomaterials, cells, molecules), axonal regrowth is facilitated to obtain a functional recovery of the neural nerve diseases. The main objective of this review is to investigate the recent approaches and applications of neural tissue engineering approaches.
Specialized Pro-resolving Lipid Mediators and Glial Cells: Emerging Candidates for Brain Homeostasis and Repair
Authors: Tiberi Marta , Chiurchiù Valerio
Published: April 2021

Astrocytes and oligodendrocytes are known to play critical roles in the central nervous system development, homeostasis and response to injury. In addition to their well-defined functions in synaptic signaling, blood-brain barrier control and myelination, it is now becoming clear that both glial cells also actively produce a wide range of immune-regulatory factors and engage in an intricate communication with neurons, microglia or with infiltrated immune cells, thus taking a center stage in both inflammation and resolution processes occurring within the brain. Resolution of inflammation is operated by the superfamily of specialized pro-resolving lipid mediators (SPMs), that include lipoxins, resolvins, protectins and maresins, and that altogether activate a series of cellular and molecular events that lead to spontaneous regression of inflammatory processes and restoration of tissue homeostasis. Here, we review the manifold effects of SPMs on modulation of astrocytes and oligodendrocytes, along with the mechanisms through which they either inhibit inflammatory pathways or induce the activation of protective ones. Furthermore, the possible role of SPMs in modulating the cross-talk between microglia, astrocytes and oligodendrocytes is also summarized. This SPM-mediated mechanism uncovers novel pathways of immune regulation in the brain that could be further exploited to control neuroinflammation and neurodegeneration.
Which Way to Choose for the Treatment of Metastatic Prostate Cancer: A Case Report and Literature Review
Authors: Yang Xiangwei , Jiang Donggen , Li Yamei , Zhang Tianzhi , Xu Duanya , Chen Xianju , Pang Jun
Published: April 2021

Background

Prostate cancer (PCa) is the second most common cancer among males in the world and the majority of patients will eventually progress to the metastatic phase. How to choose an effective way for the treatment of metastatic PCa, especially in the later stage of the disease is still confusing. Herein we reported the case of a patient diagnosed with metastatic PCa and conducted a literature review on this issue.

Case Presentation

A 57-year-old man with metastatic PCa had been managed by Dr. J.P. since April 2012 when the patient was admitted to the Third Affiliated Hospital of Sun Yat-sen University by aggravating frequent urination and dysuria. The prostate-specific antigen (PSA) concentration was 140 ng/ml, and the diagnosis of PCa was confirmed by prostate biopsy, with Gleason score 4 + 5 = 9. Chest CT and bone scan indicated multiple metastases in the lungs and bones. Triptorelin, bicalutamide, zoledronic acid, and docetaxel were then administered, six cycles later, the metastatic tumors in the lungs disappeared and those in the bones lessened significantly, along with a remarkable reduction in PSA level (< 2 ng/ml). Intermittent androgen deprivation was subsequently conducted until August 2018, when the serum PSA level was found to be 250 ng/ml, again docetaxel 75 mg/m2 was administered immediately but the patient was intolerant this time. Instead, abiraterone was administered until March 2019 because of intolerable gastrointestinal side-effects and increasing PSA level. In October 2019, the patient came to our center, a modified approach of docetaxel (day 1 40 mg/m2 + day 8 35 mg/m2) was administered. Luckily, the PSA level decreased rapidly, the bone pain was greatly relieved, and no obvious side effects occurred. However, four cycles later, docetaxel failed to work anymore, the metastatic tumor in the liver progressed. We proposed several regimens as alternatives, but they were soon denied due to the high prices or unavailability or uncertain effect of the drugs. In addition, the patient’s condition deteriorated speedily and can no longer bear any aggressive treatment. Finally, the patient died of multiple organ failure in August 2020.

Conclusion

The experiences of this case provide valuable evidence and reference for the treatment choices of metastatic PCa, in some circumstances modified and advanced regimens may produce unexpected effects.