bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Scenario Physical Energy Storage Planning of Integrated Energy Systems Considering Dynamic Characteristics of Heating Network and Demand Response
Authors: Deng Xin , Huang Yixin , Chen Yuge , Chen Changming , Yang Li , Gao Qiang , Chen Xin , Hou Wenhao , Lin Zhenzhi
Published: December 2021

The configuration of energy storage in the integrated energy system (IES) can effectively improve the consumption rate of renewable energy and the flexibility of system operation. Due to the high cost and long cycle of the physical energy storage construction, the configuration of energy storage is limited. The dynamic characteristics of the heating network and the demand-side response (DR) can realize the space-time transfer of energy. Although there is no actual energy storage equipment construction, it plays a similar role to physical energy storage and can be considered as virtual energy storage in IES planning. In this paper, a multi-scenario physical energy storage planning model of IES considering the dynamic characteristics of the heating network and DR is proposed. To make full use of the energy storage potential of the proposed model, the virtual energy storage features of the dynamic heating characteristics of the heating network and DR are analyzed at first. Next, aiming at the uncertainty of wind turbine (WT) and photovoltaic (PV) output, the scenario analysis method is used to describe the wind and photovoltaic power output with different probabilities. Finally, an electrothermal IES with an IEEE 33-node network and a 26-node heating network serves as an example to verify the effectiveness of the proposed model. The case study shows that the proposed model effectively reduces the physical energy storage configuration and achieves the economic trade-off between the investment cost and the operation cost.
Growth and Anchorage of Myriophyllum spicatum L. in Relation to Water Depth and the Content of Organic Matter in Sediment
Authors: He Liang , Wang Rui , Zhang Huan , Zhang Meng , Liu Ying , Zhu Guorong , Cao Te , Ni Leyi , Ge Gang
Published: December 2021

A large body of evidence suggests that the physical and chemical characteristics of the sediment in lakes that have undergone eutrophication have been significantly altered. However, the effects of alterations in sediments on submersed macrophytes remain unknown. In this study, we present the results of an outdoor experiment that examined how the growth and anchorage of the widespread submersed macrophyte Myriophyllum spicatum L. responded to the enrichment of organic matter in the sediments and whether water depth affects these responses. We found that low levels of enrichment with organic matter (≤7%) enhanced the growth of M. spicatum. In contrast, high levels of enrichment with organic matter (from 12 to 18%) slightly inhibited its growth. Although the anchorage force of M. spicatum slightly decreased with an increase in the content of organic matter in the sediment, it was much higher than the hydraulic drag force on plants at a relatively high current velocity, indicating that the plants were unlikely to be uprooted in these sediments. The water depth did not alter the responses of growth and anchorage of M. spicatum to enrichment with organic matter. Our results suggest that M. spicatum could be a potential species to restore eutrophic lakes, since it can grow well and anchor stably in sediments with relatively high organic matter and manage low light stress.
Optimization of a Marine Fish Release Strategy: A Case Study of Black Sea Bream Acanthopagrus schlegelii in the Zhanjiang Estuary, Northern South China Sea
Authors: Zhang Shenzeng , Lin Lin , Wang Xuefeng
Published: December 2021

The release strategy (choice of the species and locations stocked, releasing mode, and stocking size and times) is an important part of quantitative evaluations of marine fish stock enhancement, while optimization of the release strategy can contribute to assess the stocking success intended to alleviate declining fishery resources and to increase the income of fishers. In this study, a typical fish species released in the northern South China Sea, black sea bream Acanthopagrus schlegelii, was taken as the research object. The biological characteristics of this sparid were determined from samples collected from waters in the Zhanjiang estuary during June, July, and September 2020 to April 2021, and the data were applied to estimate its length frequency and its growth parameters using the ELEFAN I run in FiSAT II. We then simulated and evaluated the stocking effects of five scenarios under different release strategies, while assuming a fixed total quantity of released fish and a constant of mortality rate at different life stages. The results showed that (1) the breeding season of black sea bream in this region is mainly from December to March of the next year, which is also the period when most significant sexual reversal in this species occurs, and (2) the relationship between standard length and weight in black sea bream is W = 5.092 × 10–5L2.906, L∞ = 54.39 cm, K = 0.15, and t0 = −0.967. (3) The recommended period to release black sea bream in Zhanjiang waters is from June to October. It appears more productive if the total quantity of fish released can be divided into two batches. The growth potential of released juvenile fish in this study was evaluated based on a density-dependent theory, and the stocking effect of released stocks was simulated with the consideration for biological parameters and field sampling technique. This study provides a reference for the optimization of fish release strategies in coastal waters.
Annual Variation of Global Air Pollution: Initial Aerosol Effect or Climate Interaction?
Authors: Feng Huihui , Ding Ying , Zou Bin , Zhao Chuanfeng
Published: December 2021

The aerosol at the previous time (initial aerosol) and climate conditions control the next step annual variation of global air pollution through the complex aerosol-climate interaction. However, the individual influences remain unclear, leaving a great gap for understanding the mechanism of air pollution evolution and supporting the environment management. We estimate the annual variation using statistical methods and satellite observations at global scale from 2001 to 2016 Results show that significant variation of annual aerosol occurs over 13.6% of land areas, in which a perturbation of aerosol may cause 0.58 ± 0.45 times change in the next phase. Initial aerosol and climate influences contribute 48.4–51.6% of the total variation, respectively. Specifically, the influences of precipitation, air temperature and surface temperature represent 0.1, 18.3 and 33.2% of the total variation. Physically, the observed variation is strongly correlated with fine mode aerosols, radiative scattering and warm/hot summers in temperate and cold zones. The environmental management therefore should implement cause-oriented strategies for emission control or climatic adaption.
Translational Science Education Through Citizen Science
Authors: Young Allison M. , van Mantgem Elizabeth F. , Garretson Alexis , Noel Christine , Morelli Toni Lyn
Published: December 2021

Guided by the six elements of Translational Ecology (TE; i.e., decision-framing, collaboration, engagement, commitment, process, and communication), we showcase the first explicit example of a Translational Science Education (TSE) effort in the coastal redwood ecosystem of Humboldt County, CA. Using iNaturalist, a flexible and free citizen science/crowdsourcing app, we worked with students from grade school through college, and their teachers and community, to generate species lists for comparison among 19 school and non-profit locations spanning a range of urbanization. Importantly, this TSE effort resulted in both learning and data generation, highlighting the ability of a TSE framework to connect and benefit both students and researchers. Our data showed that, regardless of the age of the observers, holding organized BioBlitzes added substantially more species to local biodiversity lists than would have been generated without them. In support of current ecological theory, these data showed an urbanization gradient among sites, with rural sites containing fewer non-native species than urban ones. On the education side, qualitative assessments revealed students and educators remained engaged throughout the project. Future projects would also benefit by establishing quantifiable metrics for assessing student learning from project conception. Throughout the project, the fundamentals of TE were followed with repeated interactions and shared objectives developed over time within trusted community relationships. Such positive human interactions can lead new naturalists to think of themselves as champions of their local biodiversity (i.e., as land stewards). We anticipate that such newly empowered and locally expert naturalists will remain committed to land stewardship in perpetuity and that other scientists and educators are inspired to conduct similar work.
A Stepwise-Clustered Simulation Approach for Projecting Future Heat Wave Over Guangdong Province
Authors: Ren Jiayan , Huang Guohe , Li Yongping , Zhou Xiong , Xu Jinliang , Yang Zhifeng , Tian Chuyin , Wang Feng
Published: December 2021

A heat wave is an important meteorological extreme event related to global warming, but little is known about the characteristics of future heat waves in Guangdong. Therefore, a stepwise-clustered simulation approach driven by multiple global climate models (i.e., GCMs) is developed for projecting future heat waves over Guangdong under two representative concentration pathways (RCPs). The temporal-spatial variations of four indicators (i.e., intensity, total intensity, frequency, and the longest duration) of projected heat waves, as well as the potential changes in daily maximum temperature (i.e., Tmax) for future (i.e., 2006–2095) and historical (i.e., 1976–2005) periods, were analyzed over Guangdong. The results indicated that Guangdong would endure a notable increasing annual trend in the projected Tmax (i.e., 0.016–0.03°C per year under RCP4.5 and 0.027–0.057°C per year under RCP8.5). Evaluations of the multiple GCMs and their ensemble suggested that the developed approach performed well, and the model ensemble was superior to any single GCM in capturing the features of heat waves. The spatial patterns and interannual trends displayed that Guangdong would undergo serious heat waves in the future. The variations of intensity, total intensity, frequency, and the longest duration of heat wave are likely to exceed 5.4°C per event, 24°C, 25 days, and 4 days in the 2080s under RCP8.5, respectively. Higher variation of those would concentrate in eastern and southwestern Guangdong. It also presented that severe heat waves with stronger intensity, higher frequency, and longer duration would have significant increasing tendencies over all Guangdong, which are expected to increase at a rate of 0.14, 0.83, and 0.21% per year under RCP8.5, respectively. Over 60% of Guangdong would suffer the moderate variation of heat waves to the end of this century under RCP8.5. The findings can provide decision makers with useful information to help mitigate the potential impacts of heat waves on pivotal regions as well as ecosystems that are sensitive to extreme temperature.
Revalidation of Mazama rufa (Illiger 1815) (Artiodactyla: Cervidae) as a Distinct Species out of the Complex Mazama americana (Erxleben 1777)
Authors: Peres Pedro H. F. , Luduvério Douglas J. , Bernegossi Agda Maria , Galindo David J. , Nascimento Guilherme B. , Oliveira Márcio L. , Sandoval Eluzai Dinai Pinto , Vozdova Miluse , Kubickova Svatava , Cernohorska Halina , Duarte José Maurício Barbanti
Published: December 2021

The red brocket deerMazama americanaErxleben, 1777 is considered a polyphyletic complex of cryptic species with wide chromosomal divergence. Evidence indicates that the observed chromosomal divergences result in reproductive isolation. The description of a neotype forM. americanaallowed its genetic characterization and represented a comparative basis to resolve the taxonomic uncertainties of the group. Thus, we designated a neotype for the synonymMazama rufaIlliger, 1815 and tested its recognition as a distinct species from theM. americanacomplex with the analysis of morphological, cytogenetic and molecular data. We also evaluated its distribution by sampling fecal DNA in the wild. Morphological data from craniometry and body biometry indicated an overlap of quantitative measurements betweenM. rufaand the entireM. americanacomplex. The phylogenetic hypothesis obtained through mtDNA confirmed the reciprocal monophyly relationship betweenM. americanaandM. rufa, and both were identified as distinct molecular operational taxonomic units by the General Mixed Yule Coalescent species delimitation analysis. Finally, classic cytogenetic data and fluorescence in situ hybridization with whole chromosome painting probes showedM. rufawith a karyotype of 2n = 52, FN = 56. Comparative analysis indicate that at least fifteen rearrangements separateM. rufaandM. americana(sensu stricto) karyotypes, which confirmed their substantial chromosomal divergence. This divergence should represent an important reproductive barrier and allow its characterization as a distinct and valid species. Genetic analysis of fecal samples demonstrated a wide distribution ofM. rufain the South American continent through the Atlantic Forest, Cerrado and south region of Amazon. Thus, we conclude for the revalidation ofM. rufaas a distinct species under the concept of biological isolation, with its karyotype as the main diagnostic character. The present work serves as a basis for the taxonomic review of theM. americanacomplex, which should be mainly based on cytogenetic characterization and directed towards a better sampling of the Amazon region, the evaluation of available names in the species synonymy and a multi-locus phylogenetic analysis.
Case Report: A Case of Hailey–Hailey Disease Mimicking Condyloma Acuminatum and a Novel Splice-Site Mutation of ATP2C1 Gene
Authors: Dai Yuwei , Yu Lingling , Wang Yu , Gao Min , Wang Peiguang
Published: December 2021

Hailey–Hailey disease (HHD) is a rare autosomal-dominant blistering disorder characterized by recurrent vesicular and erosive lesions at intertriginous sites. We described a 24-year-old male who presented with multiple bright red verrucous papules in his mons pubis, bilateral groins, scrotum, perineum, and crissum, clinically resembling condyloma acuminatum. The histopathology showed extensive acantholysis with the characteristic appearance of a dilapidated brick-wall. The mutation analysis revealed a novel splice-site mutation in the ATP2C1 gene. The patient was definitely diagnosed with HHD. The antibacterial treatments resulted in a dramatic improvement. Our findings help to broaden the understanding of clinical manifestations of HHD and improve the clinical diagnosis and treatment of this disease.
An Improved Memetic Algorithm for Detecting Protein Complexes in Protein Interaction Networks
Authors: Wang Rongquan , Ma Huimin , Wang Caixia
Published: December 2021

Identifying the protein complexes in protein-protein interaction (PPI) networks is essential for understanding cellular organization and biological processes. To address the high false positive/negative rates of PPI networks and detect protein complexes with multiple topological structures, we developed a novel improved memetic algorithm (IMA). IMA first combines the topological and biological properties to obtain a weighted PPI network with reduced noise. Next, it integrates various clustering results to construct the initial populations. Furthermore, a fitness function is designed based on the five topological properties of the protein complexes. Finally, we describe the rest of our IMA method, which primarily consists of four steps: selection operator, recombination operator, local optimization strategy, and updating the population operator. In particular, IMA is a combination of genetic algorithm and a local optimization strategy, which has a strong global search ability, and searches for local optimal solutions effectively. The experimental results demonstrate that IMA performs much better than the base methods and existing state-of-the-art techniques. The source code and datasets of the IMA can be found at https://github.com/RongquanWang/IMA.
Acceptability and Satisfaction of Contraceptive Vaginal Rings in Clinical Studies: A Systematic Review and Narrative Synthesis
Authors: Delvaux Thérèse , Jespers Vicky , Benova Lenka , van de Wijgert Janneke
Published: December 2021

Introduction: Acceptability of and satisfaction with contraceptive methods are paramount for uptake and continuation. In the current context of multipurpose prevention of pregnancy and sexually transmitted diseases/HIV development, it is critical to have a better understanding of acceptability of and satisfaction with the contraceptive vaginal ring (CVR) including sexual satisfaction. The objective of this study was to review the evidence about acceptability of CVRs and general and sexual satisfaction of users.

Methods: We searched PubMed, CINAHL, and Web of Science (until December 31, 2020) and selected original studies documenting actual use of hormonal CVR and explicitly addressing any of the 3 outcomes.

Results: Of a total of 1,129 records screened, 46 studies were included. Most studies (n = 43, 93%) were prospective, conducted in high-income settings (n = 35), and reported on NuvaRing® use (n = 31). Overall, 27 (59%) studies included a comparison group, 38 (82%) studies used exclusively quantitative questionnaires, with qualitative only (n = 4, 9%), or mixed methods (n = 4, 9%) studies being less common. Ease of CVR insertion/removal/reinsertion was high in all the settings and improved with time of use, with qualitative studies supporting these findings. When mentioned, ring-related events were associated with discontinuation, and results on continuation of use were mixed. Among NuvaRing® studies, general satisfaction (being satisfied or very satisfied) was between 80 and 90% and tended to mirror continuation. Sexual satisfaction was less commonly reported and results were mixed. Overall, limited information was provided on actual CVR experiences of women (and men) and cultural norms that may affect sexuality and CVR use.

Conclusion: Positive aspects of acceptability of and satisfaction with CVRs were reported, but ring-related events and factors, which may affect long-term CVR use, deserve further study. More information is needed on actual experiences of women using CVRs, relationship aspects, male partner opinions, and contextual norms to better understand the acceptability of and satisfaction with CVRs.
A Recent Update on Advanced Molecular Diagnostic Techniques for COVID-19 Pandemic: An Overview
Authors: Roberts Akanksha , Chouhan Raghuraj Singh , Shahdeo Deepshikha , Shrikrishna Narlawar Sagar , Kesarwani Veerbhan , Horvat Milena , Gandhi Sonu
Published: December 2021

Coronavirus disease 2019 (COVID-19), which started out as an outbreak of pneumonia, has now turned into a pandemic due to its rapid transmission. Besides developing a vaccine, rapid, accurate, and cost-effective diagnosis is essential for monitoring and combating the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its related variants on time with precision and accuracy. Currently, the gold standard for detection of SARS-CoV-2 is Reverse Transcription Polymerase Chain Reaction (RT-PCR), but it lacks accuracy, is time-consuming and cumbersome, and fails to detect multi-variant forms of the virus. Herein, we have summarized conventional diagnostic methods such as Chest-CT (Computed Tomography), RT-PCR, Loop Mediated Isothermal Amplification (LAMP), Reverse Transcription-LAMP (RT-LAMP), as well new modern diagnostics such as CRISPR–Cas-based assays, Surface Enhanced Raman Spectroscopy (SERS), Lateral Flow Assays (LFA), Graphene-Field Effect Transistor (GraFET), electrochemical sensors, immunosensors, antisense oligonucleotides (ASOs)-based assays, and microarrays for SARS-CoV-2 detection. This review will also provide an insight into an ongoing research and the possibility of developing more economical tools to tackle the COVID-19 pandemic.
Myosin 1g and 1f: A Prospective Analysis in NK Cell Functions
Authors: Cruz-Zárate David , Miguel-Rodríguez Carlos Emilio , Martínez-Vargas Irving Ulises , Santos-Argumedo Leopoldo
Published: December 2021

NK cells are contained in the ILC1 group; they are recognized for their antiviral and antitumor cytotoxic capacity; NK cells also participate in other immune response processes through cytokines secretion. However, the mechanisms that regulate these functions are poorly understood since NK cells are not as abundant as other lymphocytes, which has made them difficult to study. Using public databases, we identified that NK cells express mRNA encoding class I myosins, among which Myosin 1g and Myosin 1f are prominent. Therefore, this mini-review aims to generate a model of the probable participation of Myosin 1g and 1f in NK cells, based on information reported about the function of these myosins in other leukocytes.
HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation
Authors: Tsamadou Chrysanthi , Engelhardt Daphne , Platzbecker Uwe , Sala Elisa , Valerius Thomas , Wagner-Drouet Eva , Wulf Gerald , Kröger Nicolaus , Murawski Niels , Einsele Hermann , Schaefer-Eckart Kerstin , Freitag Sebastian , Casper Jochen , Kaufmann Martin , Dürholt Mareike , Hertenstein Bernd , Klein Stefan , Ringhoffer Mark , Frank Sandra , Neuchel Christine , Schrezenmeier Hubert , Mytilineos Joannis , Fuerst Daniel
Published: December 2021

TheHLA-DRB3/4/5loci are closely linked to theHLA-DRB1gene. Mismatches in these loci occur with a frequency of about 8%–12% in otherwise 10/10 HLA-matched transplant pairs. There is preliminary evidence that these disparities may associate with increased acute graft-versus-host disease (GvHD) rates. The aim of this study was to analyze a large cohort of German patients and their donors forHLA-DRB3/4/5compatibility and to correlate theHLA-DRB3/4/5matching status with the outcome of unrelated hematopoietic stem cell transplantation (uHSCT). To this end, 3,410 patients and their respective donors wereHLA-DRB3/4/5andHLA-DPB1typed by amplicon-based next-generation sequencing (NGS). All patients included received their first allogeneic transplant for malignant hematologic diseases between 2000 and 2014. Mismatches in the antigen recognition domain (ARD) ofHLA-DRB3/4/5genes were correlated with clinical outcome.HLA-DRB3/4/5incompatibility was seen in 12.5% (n = 296) and 17.8% (n = 185) of the 10/10 and 9/10 HLA-matched cases, respectively.HLA-DRB3/4/5mismatches in the ARD associated with a worse overall survival (OS), as shown in univariate (5-year OS: 46.1% vs. 39.8%, log-rank p = 0.038) and multivariate analyses [hazard ratio (HR) 1.25, 95% CI 1.02–1.54, p = 0.034] in the otherwise 10/10 HLA-matched subgroup. The worse outcome was mainly driven by a significantly higher non-relapse mortality (HR 1.35, 95% CI 1.05–1.73, p = 0.017). In the 9/10 HLA-matched cases, the effect was not statistically significant. Our study results suggest that mismatches within the ARD ofHLA-DRB3/4/5genes significantly impact the outcome of otherwise fully matched uHSCT and support their consideration upon donor selection in the future.
Association of IL-9, IL-10, and IL-17 Cytokines With Hepatic Fibrosis in Human Schistosoma mansoni Infection
Authors: Franco Karine Garcez Schuster , de Amorim Fabio Jorge Ramalho , Santos Mário Adriano , Rollemberg Carla Virgínia Vieira , de Oliveira Fabricia Alvisi , França Alex Vianey Callado , Santos Camilla Natália Oliveira , Magalhães Lucas Sousa , Cazzaniga Rodrigo Anselmo , de Lima Frederico Santana , Benevides Luciana , Carregaro Vanessa , Silva João Santana , Brito Hugo Leite de Farias , Fernandes Daniel Alvarenga , da Silva Ângela Maria , de Almeida Roque Pacheco , Bezerra-Santos Márcio , de Jesus Amélia Ribeiro
Published: December 2021

This is a case series study to evaluate immunological markers associated with schistosomiasis advanced fibrosis, including 69 patients from an endemic area from the State of Sergipe and from the Hepatology Service of the University Hospital in Sergipe, Brazil. Hepatic fibrosis was classified based on Niamey protocol for ultrasonography (US). Immune response toSchistosoma mansoniantigens was evaluated by stimulating peripheral blood mononuclear cells (PBMCs) from these patients with either adult worm (SWAP—10 μg/ml) or egg (SEA—10 μg/ml) antigens or purified protein derivative of turberculin (PPD—10 μg/ml) or phytohemagglutinin (PHA—1 μg/ml) for 72 h. The levels of IFN-γ, TNF-α, IL-5, IL-10, and IL-17 were measured in these supernatants by ELISA and IL-9 by Luminex. Single nucleotide polymorphisms inIL-17,IL10, andCD209genes were genotyped using TaqMan probe by qPCR. Higher levels of IL-9, IL-10, and IL-17 were found in PBMC supernatants of patients with advanced hepatic fibrosis. Direct correlations were detected between IL-9 and IL-17 levels with US spleen sizes, portal vein diameters, and periportal thickening. TheCD209rs2287886 AG polymorphism patients produce higher IL-17 levels. Together, these data suggest a role of these cytokines in the immunopathogenesis of advanced fibrosis in human schistosomiasis.
Potentiating Lung Mucosal Immunity Through Intranasal Vaccination
Authors: Nelson Sean A. , Sant Andrea J.
Published: December 2021

Yearly administration of influenza vaccines is our best available tool for controlling influenza virus spread. However, both practical and immunological factors sometimes result in sub-optimal vaccine efficacy. The call for improved, or even universal, influenza vaccines within the field has led to development of pre-clinical and clinical vaccine candidates that aim to address limitations of current influenza vaccine approaches. Here, we consider the route of immunization as a critical factor in eliciting tissue resident memory (Trm) populations that are not a target of current licensed intramuscular vaccines. Intranasal vaccination has the potential to boost tissue resident B and T cell populations that reside within specific niches of the upper and lower respiratory tract. Within these niches, Trm cells are poised to respond rapidly to pathogen re-encounter by nature of their anatomic localization and their ability to rapidly deliver anti-pathogen effector functions. Unique features of mucosal immunity in the upper and lower respiratory tracts suggest that antigen localized to these regions is required for the elicitation of protective B and T cell immunity at these sites and will need to be considered as an important attribute of a rationally designed intranasal vaccine. Finally, we discuss outstanding questions and areas of future inquiry in the field of lung mucosal immunity.
Intra-Annual Variation in Mesophotic Benthic Assemblages on the Insular Slope of Southwest Puerto Rico as a Function of Depth and Geomorphology
Authors: Appeldoorn Richard S. , Ballantine David L. , Carlo Milton , Cruz Motta Juan J. , Nemeth Michael , Ruiz Hector J. , Schizas Nikolaos V. , Sherman Clark E. , Weil Ernesto , Yoshioka Paul M.
Published: December 2021

There is limited information on the intra-annual variability of mesophotic coral ecosystems (MCEs), worldwide. The benthic communities, measured as % cover, of two geomorphologically different mesophotic sites (El Hoyo and Hole-in-the-Wall) were examined during 2009–2010 in southwest Puerto Rico. Depths sampled were 50 and 70 m. At each site/depth combination, two permanent transects, measuring 10-m long by 40-cm wide, were surveyed by successive photoquadrants, 0.24 m2 in area. Scleractinian corals, octocorals, macroalgae, crustose coralline algae (CCA), sponges and unconsolidated sediment were the main components along the transects. Significant community differences were observed both among sites and among depths. Differences among sites were greater at 50 m than at 70 m. The El Hoyo site at 50 m was the most divergent, and this was due to a lower coral and sponge cover and a higher algal cover (Amphiroa spp., Peyssonnelia iridescens, turf) relative to the other site/depth combinations. As a consequence, the differences in community structure with depth were larger at El Hoyo than at Hole-in-the-Wall. The communities at 70 m were distinguished from those at 50 m by the greater proportion of the corals Agaricia undata, Madracis pharensis and CCA, and a reduced cover of the cyanobacterium Schizothrix. Temporal variation in the benthic assemblages was documented throughout the year. For both mesophotic sites, the magnitude of change at 50 m was significantly greater than at 70 m. For both depths, the magnitude of change at El Hoyo was significantly greater than at Hole-in-the-Wall. All assemblages experienced almost the same temporal patterns, despite the differences in species composition across sites and depths. Changes in temporal patterns are driven by an increase in the percent cover of the macroalgae Dictyota spp., and a decrease in the percent cover of non-colonized substrata (sand, pavement or rubble). Relatively rapid, intra-annual changes are dictated by the negative correlation between cyclic Dictyota spp. cover and open substrata cover. Other observed mechanisms for rapid community changes in the photoquadrants were diseases and collapses of substrata along with their associated fauna indicating that small-scale disturbance processes may play an important role within MCEs.
Homeostasis Regulation by Potassium Channel Subfamily K Member 3 (KCNK3) in Various Fishes
Authors: Wen Zheng-Yong , Qin Chuan-Jie , Lv Yun-Yun , Li Yan-Ping , Zou Yuan-Chao , Guo Sheng-Tao , Shi Qiong
Published: December 2021

Potassium channels are important for K+ transport and cell volume regulation, which play important roles in many biological processes such as hormone secretion, ion homeostasis, excitability, and cell development. In mammals, a total of 15 potassium channels were identified and they were divided into six subfamilies, including TALK (TALK1, TALK2, TASK2), TASK (TASK1, TASK3, TASK5), TREK (TREK1, TREK2, TRAAK), TWIK (TWIK1, TWIK2, KCNK7), THIK (THIK1, THIK2) and TRESK. TASK1, also known as potassium channel subfamily k member 3 (KCNK3), is the first member identified in the TASK subfamily. This K2P channel has potential applications in fish breeding and aquaculture industry due to its important roles in various physiological processes. Despite its functional role has been well studied in mammals; however, it is less known in fishes. In this review, we systematically summarize recent research advances of this critical potassium channel in representative fishes, such as gene number variation, tissue distribution, phylogeny, and potential homeostasis regulation role. This paper provides novel insights into the functional properties of these fish kcnk3 genes (including osmoregulation, energy homeostasis maintenance and fatty acids metabolism regulation), and also expands our knowledge about their variations among diverse fishes.
Development and Validation of a Prognostic Signature Associated With Tumor Microenvironment Based on Autophagy-Related lncRNA Analysis in Hepatocellular Carcinoma
Authors: Deng Yan , Zhang Feng , Sun Zhen-Gang , Wang Shuai
Published: December 2021

Objective: The present study aimed to establish a prognostic signature based on the autophagy-related long non-coding RNAs (lncRNAs) analysis in patients with hepatocellular carcinoma (HCC).

Methods: Patients with HCC from The Cancer Genome Atlas (TCGA) were taken as the training cohort, and patients from the International Cancer Genome Consortium (ICGC) were treated as the validation cohort. Autophagy-related lncRNAs were obtained via a co-expression network analysis. According to univariate and multivariate analyses, a multigene prognostic signature was constructed in the training cohort. The predictive power of the signature was confirmed in both cohorts. The detailed functions were investigated using functional analysis. The single-sample gene set enrichment analysis (ssGSEA) score was used to evaluate the tumor microenvironment. The expression levels of immunotherapy and targeted therapy targets between the two risk groups were compared. Finally, a nomogram was constructed by integrating clinicopathological parameters with independently predictive value and the risk score.

Results: Four autophagy-related lncRNAs were identified to establish a prognostic signature, which separated patients into high- and low-risk groups. Survival analysis showed that patients in the high-risk group had a shorter survival time in both cohorts. A time-independent receiver-operating characteristic (ROC) curve and principal component analysis (PCA) confirmed that the prognostic signature had a robust predictive power and reliability in both cohorts. Functional analysis indicated that the expressed genes in the high-risk group are mainly enriched in autophagy- and cancer-related pathways. ssGSEA revealed that the different risk groups were associated with the tumor microenvironment. Moreover, the different risk groups had positive correlations with the expressions of specific mutant genes. Multivariate analysis showed that the risk score also exhibited excellent predictive power irrespective of clinicopathological characteristics in both cohorts. A nomogram was established. The nomogram showed good discrimination, with Harrell's concordance index (C-index) of 0.739 and good calibration.

Conclusion: The four autophagy-related lncRNAs could be used as biological biomarkers and therapeutic targets. The prognostic signature and nomogram might aid clinicians in individual treatment optimization and clinical decision-making for patients with HCC.
Insights Into the Inhibition of MOX-1 β-Lactamase by S02030, a Boronic Acid Transition State Inhibitor
Authors: Ishikawa Tatsuya , Furukawa Nayuta , Caselli Emilia , Prati Fabio , Taracila Magdalena A. , Bethel Christopher R. , Ishii Yoshikazu , Shimizu-Ibuka Akiko , Bonomo Robert A.
Published: December 2021

The rise of multidrug resistant (MDR) Gram-negative bacteria has accelerated the development of novel inhibitors of class A and C β-lactamases. Presently, the search for novel compounds with new mechanisms of action is a clinical and scientific priority. To this end, we determined the 2.13-Å resolution crystal structure of S02030, a boronic acid transition state inhibitor (BATSI), bound to MOX-1 β-lactamase, a plasmid-borne, expanded-spectrum AmpC β-lactamase (ESAC) and compared this to the previously reported aztreonam (ATM)-bound MOX-1 structure. Superposition of these two complexes shows that S02030 binds in the active-site cavity more deeply than ATM. In contrast, the SO3 interactions and the positional change of the β-strand amino acids from Lys315 to Asn320 were more prominent in the ATM-bound structure. MICs were performed using a fixed concentration of S02030 (4 μg/ml) as a proof of principle. Microbiological evaluation against a laboratory strain of Escherichia coli expressing MOX-1 revealed that MICs against ceftazidime are reduced from 2.0 to 0.12 μg/ml when S02030 is added at a concentration of 4 μg/ml. The IC50 and Ki of S02030 vs. MOX-1 were 1.25 ± 0.34 and 0.56 ± 0.03 μM, respectively. Monobactams such as ATM can serve as informative templates for design of mechanism-based inhibitors such as S02030 against ESAC β-lactamases.
Comparative Genomic Analysis of Labrenzia aggregata (Alphaproteobacteria) Strains Isolated From the Mariana Trench: Insights Into the Metabolic Potentials and Biogeochemical Functions
Authors: Zhong Haohui , Sun Hao , Liu Ronghua , Zhan Yuanchao , Huang Xinyu , Ju Feng , Zhang Xiao-Hua
Published: December 2021

Hadal zones are marine environments deeper than 6,000 m, most of which comprise oceanic trenches. Microbes thriving at such depth experience high hydrostatic pressure and low temperature. The genomic potentials of these microbes to such extreme environments are largely unknown. Here, we compare five complete genomes of bacterial strains belonging to Labrenzia aggregata (Alphaproteobacteria), including four from the Mariana Trench at depths up to 9,600 m and one reference from surface seawater of the East China Sea, to uncover the genomic potentials of this species. Genomic investigation suggests all the five strains of L. aggregata as participants in nitrogen and sulfur cycles, including denitrification, dissimilatory nitrate reduction to ammonium (DNRA), thiosulfate oxidation, and dimethylsulfoniopropionate (DMSP) biosynthesis and degradation. Further comparisons show that, among the five strains, 85% gene functions are similar with 96.7% of them encoded on the chromosomes, whereas the numbers of functional specific genes related to osmoregulation, antibiotic resistance, viral infection, and secondary metabolite biosynthesis are majorly contributed by the differential plasmids. A following analysis suggests the plasmidic gene numbers increase along with isolation depth and most plasmids are dissimilar among the five strains. These findings provide a better understanding of genomic potentials in the same species throughout a deep-sea water column and address the importance of externally originated plasmidic genes putatively shaped by deep-sea environment.
Intra- and Extra-Hospital Dissemination of IMP-22-Producing Klebsiella pneumoniae in Northern Portugal: The Breach of the Hospital Frontier Toward the Community
Authors: Gonçalves Daniela , Cecílio Pedro , Faustino Alberta , Iglesias Carmen , Branca Fernando , Estrada Alexandra , Ferreira Helena
Published: December 2021

The emergence of infections (and colonization) with Enterobacteriaceae-producing carbapenemases is a threatening public health problem. In the last decades, we watched an isolated case becoming a brutal outbreak, a sporadic description becoming an endemic problem. The present study aims to highlight the dissemination of IMP-22-producing Klebsiella pneumoniae in the North of Portugal, through the phenotypic and genotypic characterization of isolates collected from hospitalized patients (n=5) and out-patients of the emergency ward of the same acute care hospital (n=2), and isolates responsible for the intestinal colonization of residents in a Long-Term Care Facility (n=4). Pulsed-field gel electrophoresis (PFGE) results, associated with conjugation experiments pointed to a pattern of both vertical and horizontal dissemination. Overall, and complementing other studies that give relevance to IMP-22-producing K. pneumoniae in the clinical settings, here we show for the first time the public health threatening breach of the hospital frontier of this resistance threat, toward the community.
Pharmacodynamics of Linezolid Plus Fosfomycin Against Vancomycin–Resistant Enterococcus faecium in a Hollow Fiber Infection Model
Authors: Wang Shuaishuai , Liu Huiping , Mao Jun , Peng Yu , Yan Yisong , Li Yaowen , Zhang Na , Jiang Lifang , Liu Yanyan , Li Jiabin , Huang Xiaohui
Published: December 2021

The optimal therapy for severe infections caused by vancomycin-resistant Enterococcus faecium (VREfm) remains unclear, but the combination of linezolid and fosfomycin may be a good choice. The 24-h static-concentration time-kill study (SCTK) was used to preliminarily explore the pharmacodynamics of linezolid combined with fosfomycin against three clinical isolates. Subsequently, a hollow-fibre infection model (HFIM) was used for the first time to further investigate the pharmacodynamic activity of the co-administration regimen against selected isolates over 72 h. To further quantify the relationship between fosfomycin resistance and bacterial virulence in VREfm, the Galleria mellonella infection model and virulence genes expression experiments were also performed. The results of SCTK showed that the combination of linezolid and fosfomycin had additive effect on all strains. In the HFIM, the dosage regimen of linezolid (12 mg/L, steady-state concentration) combined with fosfomycin (8 g administered intravenously every 8 h as a 1 h infusion) not only produced a sustained bactericidal effect of 3∼4 log10 CFU/mL over 72 h, but also completely eradicated the resistant subpopulations. The expression of virulence genes was down-regulated to at least 0.222-fold in fosfomycin-resistant strains compared with baseline isolate, while survival rates of G. mellonella was increased (G. mellonella survival ≥45% at 72 h). For severe infections caused by VREfm, neither linezolid nor fosfomycin monotherapy regimens inhibited amplification of the resistant subpopulations, and the development of fosfomycin resistance was at the expense of the virulence of VREfm. The combination of linezolid with fosfomycin produced a sustained bactericidal effect and completely eradicated the resistant subpopulations. Linezolid plus Fosfomycin is a promising combination for therapy of severe infections caused by VREfm.
Identification of Novel Phage Resistance Mechanisms in Campylobacter jejuni by Comparative Genomics
Authors: Sørensen Martine C. H. , Gencay Yilmaz Emre , Fanger Florian , Chichkova Mariana A. T. , Mazúrová Mária , Klumpp Jochen , Nielsen Eva M. , Brøndsted Lone
Published: December 2021

Phages infecting Campylobacter jejuni are considered a promising intervention strategy at broiler farms, yet phage sensitivity of naturally occurring poultry isolates is not well studied. Here, we investigated phage sensitivity and identified resistance mechanisms of C. jejuni strains originating from Danish broilers belonging to the most prevalent MLST (ST) types. Determining plaque formation of 51 phages belonging to Fletchervirus or Firehammervirus showed that 21 out of 31 C. jejuni strains were susceptible to at least one phage. While C. jejuni ST-21 strains encoded the common phase variable O-methyl phosphoramidate (MeOPN) receptor of the Fletchervirus and were only infected by these phages, ST-45 strains did not encode this receptor and were exclusively infected by Firehammervirus phages. To identify internal phage resistance mechanism in ST-21 strains, we performed comparative genomics of two strains, CAMSA2002 sensitive to almost all Fletchervirus phages and CAMSA2038, resistant to all 51 phages. The strains encoded diverse clustered regularly interspaced short palindromic repeats (CRISPR) spacers but none matched the tested phages. Sequence divergence was also observed in a predicted SspE homolog and putative restriction modification systems including a methyl-specific McrBC endonuclease. Furthermore, when mcrB was deleted, CAMSA2038 became sensitive to 17 out of 43 phages, three being Firehammervirus phages that otherwise did not infect any ST-21 strains. Yet, 16 phages demonstrated significantly lower efficiencies of plating on the mcrB mutant suggesting additional resistance mechanism still restricting phage propagation in CAMSA2038. Thus, our work demonstrates that C. jejuni isolates originating from broilers may have acquired several resistance mechanisms to successfully prevent phage infection in their natural habitat.
A Novel Formononetin Derivative Promotes Anti-ischemic Effects on Acute Ischemic Injury in Mice
Authors: Zhao Lin , Han Jing , Liu Jiaqi , Fan Kechen , Yuan Tianjie , Han Ju , Chen Liangliang , Zhang Sen , Zhao Ming , Duan Jinao
Published: December 2021

Natural flavonoids, formononetin and ononin, possess antioxidant, antibacterial, anti-inflammatory and neuroprotective effects. Many complications caused by SARS-CoV-2 make patients difficult to recover. Flavonoids, especially formononetin and ononin, have the potential to treat SARS-CoV-2 and improve myocardial injury. However, their poor water solubility, poor oral absorption, high toxicity, and high-cost purification limit industrial practical application. Succinylation modification provides a solution for the above problems. Formononetin-7-O-β-(6″-O-succinyl)-D-glucoside (FMP), a new compound, was succinyl glycosylated from formononetin by the organic solvent tolerant bacteria Bacillus amyloliquefaciens FJ18 in a 10.0% DMSO (v/v) system. The water solubility of the new compound was improved by over 106 times compared with formononetin, which perfectly promoted the application of formononetin and ononin. The conversion rate of formononetin (0.5 g/L) was almost 94.2% at 24 h, while the yield of formononetin-7-O-β-(6″-O-succinyl)-D-glucoside could achieve 97.2%. In the isoproterenol (ISO)-induced acute ischemia mice model, the myocardial injury was significantly improved with a high dose (40 mg/kg) of formononetin-7-O-β-(6″-O-succinyl)-D-glucoside. The lactate dehydrogenase level was decreased, and the catalase and superoxide dismutase levels were increased after formononetin-7-O-β-(6″-O-succinyl)-D-glucoside treatment. Thus, formononetin-7-O-β-(6″-O-succinyl)-D-glucoside has high water solubility, low toxicity, and shows significant antimyocardial ischemia effects.
Evaluation of the in vitro Activity and in vivo Efficacy of Anidulafungin-Loaded Human Serum Albumin Nanoparticles Against Candida albicans
Authors: Zhang Yu , Liu Yan-Chao , Chen Si-Min , Zong Hui , Hou Wei-Tong , Qiu Xi-Ran , Guo Shi-Yu , Sun Yu-Fang , Jiang Yuan-Ying , An Mao-Mao , Shen Hui
Published: December 2021

Recent decades have seen a significant increase in invasive fungal infections, resulting in unacceptably high mortality rates. Anidulafungin (AN) is the newest echinocandin and appears to have several advantages over existing antifungals. However, its poor water solubility and burdensome route of administration (i.e., repeated, long-term intravenous infusions) have limited its practical use. The objective of this study was to develop anidulafungin-loaded Human Serum Albumin (HSA) nanoparticles (NP) so as to increase both its solubility and antifungal efficacy. HSA was reduced using SDS and DTT, allowing liberation of free thiols to form the intermolecular disulfide network and nanoassembly. Reduced HSA was then added to MES buffer (0.1 M, pH 4.8) and magnetically stirred at 350 rpm and 25°C with AN (m/m 50:1) for 2 h to form nanoparticles (AN NP). We next performed routine antifungal susceptibility testing of Candida strains (n = 31) using Clinical and Laboratory Standards Institute (CLSI) methodologies. Finally, the in vivo efficacy of both AN and AN NP was investigated in a murine model of invasive infection by one of the most common fungal species—C. albicans. The results indicated that our carrier formulations successfully improved the water solubility of AN and encapsulated AN, with the latter having a particle size of 29 ± 1.5 nm with Polymer dispersity index (PDI) equaling 0.173 ± 0.039. In vitro AN NP testing revealed a stronger effect against Candida species (n = 31), with Minimum Inhibitory Concentration (MIC) values 4- to 32-fold lower than AN alone. In mice infected with Candida and having invasive candidiasis, we found that AN NP prolonged survival time (P < 0.005) and reduced fungal burden in kidneys compared to equivalent concentrations of free drug (P < 0.0001). In conclusion, the anidulafungin nanoparticles developed here have the potential to improve drug administration and therapeutic outcomes for individuals suffering from fungal diseases.