bluuebunny/crossref_metadata_2025 huggingface dataset:
Resilient Network Design: Disjoint Shortest Path Problem for Power Transmission Application
Authors: Jha Amit , Song Haotian , Zinchenko Yuriy
Published: March 2024

Path redundancy is essential for safety and reliability in many real-world routing problems, such as the design of networks for power transmission, transportation, etc. These problems are typically posed to find the shortest path on a weighted graph. For the shortest path with path redundancy, particularly in the Disjoint Shortest 2-Path (DS2P) problem, two disjoint paths are desired such that the combined weight of the two paths is minimized while a minimum distance path separation is maintained. The conventional formulation of the above requires a large-scale mixed-integer programming (MIP) model. However, this approach is practically intractable due to the model’s complexity and extremely long run-time. We demonstrate why DS2P is NP-complete and propose an efficient heuristic to find an approximate solution to the problem in a much shorter time frame. We demonstrate the approach on a realistic dataset for power transmission routing, integrating the computational methodology with a visualization interface using Google Maps. The resulting prototype software is freely available through GitHub and can be deployed on a cloud platform, such as Amazon AWS.
Enhancing Patient Care in Radiotherapy: Proof-of-Concept of a Monitoring Tool
Authors: Beldjoudi Guillaume , Eugène Rémi , Grégoire Vincent , Tanguy Ronan
Published: March 2024

Introduction: A monitoring tool, named Oncology Data Management (ODM), was developed in radiotherapy to generate structured information based on data contained in an Oncology Information System (OIS). This study presents the proof-of-concept of the ODM tool and highlights its applications to enhance patient care in radiotherapy. Material & Methods: ODM is a sophisticated SQL query which extracts specific features from the Mosaiq OIS (Elekta, UK) database into an independent structured database. Data from 2016 to 2022 was extracted to enable monitoring of treatment units and evaluation of the quality of patient care. Results: A total of 25,259 treatments were extracted. Treatment machine monitoring revealed a daily 11-treatement difference between two units. ODM showed that the unit with fewer daily treatments performed more complex treatments on diverse locations. In 2019, the implementation of ODM led to the definition of quality indicators and in organizational changes that improved the quality of care. As consequences, for palliative treatments, there was an improvement in the proportion of treatments prepared within 7 calendar days between the scanner and the first treatment session (29.1% before 2020, 40.4% in 2020 and 46.4% after 2020). The study of fractionation in breast treatments exhibited decreased prescription variability after 2019, with distinct patient age categories. Bi-fractionation once a week for larynx prescriptions of 35 × 2.0 Gy achieved an overall treatment duration of 47.0 ± 3.0 calendar days in 2022. Conclusions: ODM enables data extraction from the OIS and provides quantitative tools for improving organization of a department and the quality of patient care in radiotherapy.
Species-Specific Unbound Fraction Differences in Highly Bound PFAS: A Comparative Study across Human, Rat, and Mouse Plasma and Albumin
Authors: Ryu Sangwoo , Burchett Woodrow , Zhang Sam , Modaresi Seyed Mohamad Sadegh , Agudelo Areiza Juliana , Kaye Emily , Fischer Fabian Christoph , Slitt Angela L.
Published: March 2024

Per- and polyfluoroalkyl substances (PFAS) are a diverse group of fluorinated compounds which have yet to undergo comprehensive investigation regarding potential adverse health effects and bioaccumulative properties. With long half-lives and accumulative properties, PFAS have been linked to several toxic effects in both non-clinical species such as rat and mouse as well as human. Although biological impacts and specific protein binding of PFAS have been examined, there is no study focusing on the species-specific fraction unbound (fu) in plasma and related toxicokinetics. Herein, a presaturation equilibrium dialysis method was used to measure and validate the binding of 14 individual PFAS with carbon chains containing 4 to 12 perfluorinated carbon atoms and several functional head-groups to albumin and plasma of mouse (C57BL/6 and CD-1), rat, and human. Equivalence testing between each species-matrix combination showed positive correlation between rat and human when comparing fu in plasma and binding to albumin. Similar trends in binding were also observed for mouse plasma and albumin. Relatively high Spearman correlations for all combinations indicate high concordance of PFAS binding regardless of matrix. Physiochemical properties of PFAS such as molecular weight, chain length, and lipophilicity were found to have important roles in plasma protein binding of PFAS.
Interactive Effects of Polyethylene Microplastics and Cadmium on Growth of Microcystis aeruginosa
Authors: Xue Zihan , Xiong Zetao , Wei Zhangdong , Wang Lin , Xu Ming
Published: March 2024

Polyethylene (PE) is a common component of microplastic pollution, and cadmium (Cd) is a prevalent pollutant in contaminated freshwater bodies in China. Among cyanobacteria, Microcystis aeruginosa (M. aeruginosa) plays a crucial role in the formation of algal blooms in these water systems. However, there has been limited research on how microplastics and heavy metals affect cyanobacteria ecologically. This study aimed to evaluate the physiological effects of individual and combined exposure to Cd pollutants and microplastics on M. aeruginosa. The solutions containing 13 µm and 6.5 µm PE particles (100 mg/L) with Cd were used in the research. The results indicated that the combined treatment led to a significant inhibition of chlorophyll a content, dropping to zero by day 5. The treated groups exhibited higher microcystins (MCs) content compared to the control group, suggesting increased MCs release due to pollutant exposure. Interestingly, the adsorption of heavy metals by microplastics partially alleviated the toxicity of heavy metals on algal cells. Moreover, the combined treatment significantly suppressed catalase (CAT) activity compared to Cd treatment, indicating a synergistic effect that led to greater oxidative stress. Overall, this study provides valuable insights into the impact of PE and Cd pollution on freshwater ecosystems, elucidates the physiological responses of cyanobacteria to these pollutants, and establishes a theoretical groundwork for addressing complex water pollution using cyanobacteria-based strategies.
Embryotoxicity Induced by Triclopyr in Zebrafish (Danio rerio) Early Life Stage
Authors: Bertoni Ítalo , Sales Bianca Camargo Penteado , Viriato Cristina , Peixoto Paloma Vitória Lima , Pereira Lílian Cristina
Published: March 2024

Triclopyr, an auxin-like herbicide that is widely employed for managing weeds in food crops and pastures, has been identified in various environmental settings, particularly aquatic ecosystems. Limited understanding of the environmental fate of this herbicide, its potential repercussions for both the environment and human health, and its insufficient monitoring in diverse environmental compartments has caused it to be recognized as an emerging contaminant of concern. In this study, we have investigated how triclopyr affects zebrafish, considering a new alternative methodology. We focused on the endpoints of developmental toxicity, neurotoxicity, and behavior of zebrafish embryos and larvae. We determined that triclopyr has a 96 h median lethal concentration of 87.46 mg/L (341.01 µM). When we exposed zebrafish embryos to sublethal triclopyr concentrations (0.5, 1, 5, 10, and 50 μM) for up to 144 h, we found that 50 µM triclopyr delayed zebrafish egg hatchability. Yolk sac malabsorption was significant at 0.5, 1, 5, and 10 µM triclopyr. In zebrafish larvae, uninflated swim bladder was significant only at 50 µM triclopyr. Furthermore, zebrafish larvae had altered swimming activity after exposure to 10 µM triclopyr for 144 h. In summary, these comprehensive results indicate that even low triclopyr concentrations can elicit adverse effects during early zebrafish development.
Toxicological Effects of Naturally Occurring Endocrine Disruptors on Various Human Health Targets: A Rapid Review
Authors: Virtuoso Sara , Raggi Carla , Maugliani Antonella , Baldi Francesca , Gentili Donatella , Narciso Laura
Published: March 2024

Endocrine-disrupting compounds are chemicals that alter the normal functioning of the endocrine system of living organisms. They can be natural (N-EDCs) or synthetic compounds (S-EDCs). N-EDCs can belong to different groups, such as phytoestrogens (PEs), including flavonoids, or mycotoxins originating from plants or fungi, and cyanotoxins, derived from bacteria. Humans encounter these substances in their daily lives. The aim of this rapid review (RR) is to provide a fine mapping of N-EDCs and their toxicological effects on human health in terms of various medical conditions or adverse consequences. This work is based on an extensive literature search and follows a rigorous step-by-step approach (search strategy, analysis strategy and data extraction), to select eligible papers published between 2019 and 2023 in the PubMed database, and to define a set of aspects characterizing N-EDCs and the different human target systems. Of the N-EDCs identified in this RR, flavonoids are the most representative class. Male and female reproductive systems were the targets most affected by N-EDCs, followed by the endocrine, nervous, bone and cardiovascular systems. In addition, the perinatal, pubertal and pregnancy periods were found to be particularly susceptible to natural endocrine disruptors. Considering their current daily use, more toxicological research on N-EDCs is required.
Hormesis, the Individual and Combined Phytotoxicity of the Components of Glyphosate-Based Formulations on Algal Growth and Photosynthetic Activity
Authors: Klátyik Szandra , Takács Eszter , Barócsi Attila , Lenk Sándor , Kocsányi László , Darvas Béla , Székács András
Published: March 2024

The occurrence of the market-leading glyphosate active ingredient in surface waters is a globally observed phenomenon. Although co-formulants in pesticide formulations were considered inactive components from the aspects of the required main biological effect of the pesticide, several studies have proven the high individual toxicity of formulating agents, as well as the enhanced combined toxicity of the active ingredients and other components. Since the majority of active ingredients are present in the form of chemical mixtures in our environment, the possible combined toxicity between active ingredients and co-formulants is particularly important. To assess the individual and combined phytotoxicity of the components, glyphosate was tested in the form of pure active ingredient (glyphosate isopropylammonium salt) and herbicide formulations (Roundup Classic and Medallon Premium) formulated with a mixture of polyethoxylated tallow amines (POEA) or alkyl polyglucosides (APG), respectively. The order of acute toxicity was as follows for Roundup Classic: glyphosate < herbicide formulation < POEA. However, the following order was demonstrated for Medallon Premium: herbicide formulation < glyphosate < APG. Increased photosynthetic activity was detected after the exposure to the formulation (1.5–5.8 mg glyphosate/L and 0.5–2.2 mg POEA/L) and its components individually (glyphosate: 13–27.2 mg/L, POEA: 0.6–4.8 mg/L), which indicates hormetic effects. However, decreased photosynthetic activity was detected at higher concentrations of POEA (19.2 mg/L) and Roundup Classic (11.6–50.6 mg glyphosate/L). Differences were demonstrated in the sensitivity of the selected algae species and, in addition to the individual and combined toxicity of the components presented in the glyphosate-based herbicides. Both of the observed inhibitory and stimulating effects can adversely affect the aquatic ecosystems and water quality of surface waters.
Battle of the Bites: The Effect of Sewage Effluent Exposure on Mosquitofish Biocontrol of Mosquitoes in Residential Louisiana
Authors: Kane Emily A. , Yadav Shubham V. K. , Fogle Adeline , D’Souza Nigel A. , DeLisi Nicholas , Caillouët Kevin A.
Published: March 2024

Mosquitofish, Gambusia affinis, are eponymous larval mosquito predators. Their ability to colonize and survive in habitats that are uninhabitable by other potential predators allows them to naturally manage larval mosquito populations in most ground pools they are present in. However, effluent from residential onsite wastewater treatment systems (OWTSs) appears to limit the presence of fish predators. This is especially problematic in Louisiana, where regulations allow the discharge of OWTS effluent into open drainage conveyances. To determine the effect of effluent on the capacity of mosquitofish for biocontrol in contaminated areas, we assessed the body condition metrics of populations from two effluent-exposed sites and two sites not exposed to effluent, determined the lethal effect of effluent-contaminated drainage water on fish, and measured the prey consumption rates in the presence of effluent. Female fish collected from effluent-impacted sites had a reduced somatic body condition and most females examined displayed masculinized anal fins resembling the male gonopodium structure. This trait was not seen in fish collected from the control sites and has not yet been documented in association with OWTSs or in the state of Louisiana. Fish from the control sites survived at effluent-contaminated water levels < 70%, and the prey clearance rates increased with dilution. Onsite wastewater treatment system effluent has significant effects on both the short- and long-term persistence of mosquitofish, their body composition, reproductive health, and larval mosquito consumption. These effects likely release mosquito larvae from suppression and may increase the threat of mosquito-transmitted pathogens in effluent-contaminated locations.
The α4 Nicotinic Acetylcholine Receptor Is Necessary for the Initiation of Organophosphate-Induced Neuronal Hyperexcitability
Authors: Andrew Peter M. , Feng Wei , Calsbeek Jonas J. , Antrobus Shane P. , Cherednychenko Gennady A. , MacMahon Jeremy A. , Bernardino Pedro N. , Liu Xiuzhen , Harvey Danielle J. , Lein Pamela J. , Pessah Isaac N.
Published: March 2024

Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can produce seizures that rapidly progress to life-threatening status epilepticus. Significant research effort has been focused on investigating the involvement of muscarinic acetylcholine receptors (mAChRs) in OP-induced seizure activity. In contrast, there has been far less attention on nicotinic AChRs (nAChRs) in this context. Here, we address this data gap using a combination of in vitro and in vivo models. Pharmacological antagonism and genetic deletion of α4, but not α7, nAChR subunits prevented or significantly attenuated OP-induced electrical spike activity in acute hippocampal slices and seizure activity in mice, indicating that α4 nAChR activation is necessary for neuronal hyperexcitability triggered by acute OP exposures. These findings not only suggest that therapeutic strategies for inhibiting the α4 nAChR subunit warrant further investigation as prophylactic and immediate treatments for acute OP-induced seizures, but also provide mechanistic insight into the role of the nicotinic cholinergic system in seizure generation.
Application of β-Cyclodextrin Adsorbents in the Removal of Mixed Per- and Polyfluoroalkyl Substances
Authors: Abaie Elham , Kumar Manish , Kumar Naveen , Sun Yilang , Guelfo Jennifer , Shen Yuexiao , Reible Danny
Published: March 2024

The extensive use of per- and polyfluoroalkyl substances (PFASs) in industrial consumer products has led to groundwater contamination, raising concerns for human health and the environment. These persistent chemicals exist in different forms with varying properties, which makes their removal challenging. In this study, we assessed the effectiveness of three different β-cyclodextrin (β-CD) adsorbents at removing a mixture of PFASs, including anionic, neutral, and zwitterionic compounds, at neutral pH. We calculated linear partition coefficient (Kd) values to quantify the adsorption affinity of each PFAS. β-CD polymers crosslinked with hexamethylene diisocyanate (β-CD-HDI) and epichlorohydrin (β-CD-EPI) displayed some adsorption of PFASs. Benzyl chloride β-CD (β-CD-Cl), an adsorbent that had not been previously reported, was also synthesized and tested for PFAS adsorption. β-CD-Cl exhibited higher PFAS adsorption than β-CD-HDI and β-CD-EPI, with log Kd values ranging from 1.9 L·g−1 to 3.3 L·g−1. β-CD-Cl displayed no affinity for zwitterionic compounds, as opposed to β-CD-HDI and β-CD-EPI, which removed N-dimethyl ammonio propyl perfluorohexane sulfonamide (AmPr-FHxSA). A comparison between Kd values and the log Kow of PFAS confirmed the significant role of hydrophobic interactions in thee adsorption mechanism. This effect was stronger in β-CD-Cl, compared to β-CD-HDI and β-CD-EPI. While no effect of PFAS charge was observed in β-CD-Cl, some influence of charge was observed in β-CD-HDI and β-CD-EPI, with less negative compounds being more adsorbed. The adsorption of PFASs by β-CD-Cl was similar in magnitude to that of other adsorbents proposed in literature. However, it offers the advantage of not containing fluorine, unlike many commonly proposed adsorbents.
Meta-Analysis of the Effects of Yeast Cell Wall Extract Supple-Mentation during Mycotoxin Challenges on the Performance of Laying Hens
Authors: Weaver Alexandra C. , Weaver Daniel M. , Adams Nicholas , Yiannikouris Alexandros
Published: March 2024

A random-effects meta-analysis was conducted to investigate the effect of mycotoxins (MT) without or with the inclusion of yeast cell wall extract (YCWE, Mycosorb®, Alltech, Inc., Nicholasville, KY, USA) on laying hen performance. A total of 25 trials were collected from a literature search, and data were extracted from 8 of these that met inclusion criteria, for a total of 12 treatments and 1774 birds. Laying hens fed MT had lower (p < 0.05) body weight (BW) by −50 g, egg production by −6.3 percentage points, and egg weight by −1.95 g than control fed hens (CTRL). Inclusion of YCWE during the mycotoxin challenges (YCWE + MT) resulted in numerically greater (p = 0.441) BW by 12.5 g, while egg production and egg weight were significantly (p < 0.0001) higher by 4.2 percentage points and 1.37 g, respectively. Furthermore, economic assessment calculations indicated that YCWE may not only support hen performance but also resulted in a positive return on investment. In conclusion, mycotoxins can play a role in negatively impacting laying hen performance and profitability. Inclusion of YCWE in feed with mycotoxin challenges provided benefits to egg production and egg weight and may support profitability. As such, the inclusion of YCWE could play an important role in minimizing mycotoxin effects and in turn aid farm efficiency and profitability.
Dynamical Analysis of the Redshift Drift in FLRW Universes
Authors: Lobo Francisco S. N. , Mimoso José Pedro , Santiago Jessica , Visser Matt
Published: March 2024

Redshift drift is the phenomenon whereby the observed redshift between an emitter and observer comoving with the Hubble flow in an expanding FLRW universe will slowly evolve—on a timescale comparable to the Hubble time. In a previous article, three of the current authors performed a cosmographic analysis of the redshift drift in an FLRW universe, temporarily putting aside the issue of dynamics (the Friedmann equations). In the current article, we add dynamics while still remaining within the framework of an exact FLRW universe. We developed a suitable generic matter model and applied it to both standard FLRW and various dark energy models. Furthermore, we present an analysis of the utility of alternative cosmographic variables to describe the redshift drift data.
A Very-High-Energy Gamma-Ray View of the Transient Sky
Authors: Carosi Alessandro , López-Oramas Alicia
Published: March 2024

The development of the latest generation of Imaging Atmospheric Cherenkov Telescopes (IACTs) over recent decades has led to the discovery of new extreme astrophysical phenomena in the very-high-energy (VHE, E > 100 GeV) gamma-ray regime. Time-domain and multi-messenger astronomy are inevitably connected to the physics of transient VHE emitters, which show unexpected (and mostly unpredictable) flaring or exploding episodes at different timescales. These transients often share the physical processes responsible for the production of the gamma-ray emission, through cosmic-ray acceleration, magnetic reconnection, jet production and/or outflows, and shocks interactions. In this review, we present an up-to-date overview of the VHE transients field, spanning from novae to supernovae, neutrino counterparts or fast radio bursts, among others, and we outline the expectations for future facilities.
Standard and Non-Standard Aspects of Neutrino Physics
Authors: Granelli Alessandro
Published: March 2024

This review provides a succinct overview of the basic aspects of neutrino physics. The topics covered include neutrinos in the standard model and the three-neutrino mixing scheme; the current status of neutrino oscillation measurements and what remains to be determined; the seesaw mechanisms for neutrino mass generation and the associated phenomenology, including the leptogenesis mechanism to explain the observed matter–antimatter asymmetry of the Universe; and models for the origin of the pattern of neutrino mixing and lepton masses based on discrete flavour symmetries and modular invariance.
Elliptical Space with the McVittie Metrics
Authors: Yershov Vladimir N.
Published: March 2024

The main feature of elliptical space—the topological identification of its antipodal points—could be fundamental for understanding the nature of the cosmological redshift. The physical interpretation of the mathematical (topological) structure of elliptical space is made by using physical connections in the form of Einstein-Rosen bridges (also called “wormholes”). The Schwarzschild metric of these structures embedded into a dynamic (expanding) spacetime corresponds to McVittie’s solution of Einstein’s field equations. The cosmological redshift of spectral lines of remote sources in this metric is a combination of gravitational redshift and the time-dependent scale factor of the Friedmann-Lemaitre-Robertson-Walker metric. I compare calculated distance moduli of type-Ia supernovae, which are commonly regarded as “standard candles” in cosmology, with the observational data published in the catalogue “Pantheon+”. The constraint based on these accurate data gives a much smaller expansion rate of the Universe than is currently assumed by modern cosmology, the major part of the cosmological redshift being gravitational by its nature. The estimated age of the Universe within the discussed model is 1.48·1012 yr, which is more than two orders of magnitude larger than the age assumed by using the standard cosmological model parameters.
Primordial Black Holes from Spatially Varying Cosmological Constant Induced by Field Fluctuations in Extra Dimensions
Authors: Popov Arkady A. , Rubin Sergey G. , Sakharov Alexander S.
Published: March 2024

The origin and evolution of supermassive black holes (SMBHs) in our universe have sparked controversy. In this study, we explore the hypothesis that some of these black holes may have seeded from the direct collapse of dark energy domains with density significantly higher than the surrounding regions. The mechanism of the origin of such domains relies on the inflationary evolution of a scalar field acting in D dimensions, which is associated with the cosmological constant in our four-dimensional spacetime manifold. Inner space quantum fluctuations of the field during inflation are responsible for the spatial variations of the dark energy density in our space. This finding holds particular significance, especially considering recent evidence from pulsar timing array observations, which supports the existence of a stochastic gravitational wave background consisting of SMBH mergers.
Performance Metrics for Implementation of Americans with Disabilities Act Transition Plans
Authors: Eisenberg Yochai , Hayes Mackenzie , Hofstra Amy , Labbé Delphine , Gould Robert , Jones Robin
Published: March 2024

Safely walking or wheeling in a wheelchair in the community is a civil and human right. Some progress has been made in the US towards making walking/wheeling paths more accessible for people with disabilities through the construction of new curb ramps, fixing sidewalk barriers, and installing accessible pedestrian signals. However, pedestrians with disabilities continue to be limited by infrastructure barriers on sidewalks and streets. To encourage progress and government transparency, we developed a set of performance metrics for local governments to monitor and report their progress in implementing barrier removal plans, called Americans with Disabilities Act (ADA) transition plans. We used the five-step Nominal Group Technique to systematically develop and prioritize a set of performance metrics with an expert panel of ADA coordinators, disability organizations, and state and federal Department of Transportation staff. The research resulted in obtaining 53 metrics across five goals and 14 objectives that can be used to measure all phases of implementation and are intended to be customized to fit different community contexts and capacities. The metrics could be used by federal and state transportation agencies, as well as internationally, with some adaptation to ensure that adequate progress in barrier removal is being made. Local governments can use the metrics to document and communicate their progress and effectively reduce ADA compliance litigation concerns.
Comparative Performance in the Detection of Four Coronavirus Genera from Human, Animal, and Environmental Specimens
Authors: Wacharapluesadee Supaporn , Thippamom Nattakarn , Hirunpatrawong Piyapha , Rattanatumhi Khwankamon , Sterling Spencer L. , Khunnawutmanotham Wiparat , Noradechanon Kirana , Maneeorn Patarapol , Buathong Rome , Paitoonpong Leilani , Putcharoen Opass
Published: March 2024

Emerging coronaviruses (CoVs) are understood to cause critical human and domestic animal diseases; the spillover from wildlife reservoirs can result in mild and severe respiratory illness in humans and domestic animals and can spread more readily in these naïve hosts. A low-cost CoV molecular method that can detect a variety of CoVs from humans, animals, and environmental specimens is an initial step to ensure the early identification of known and new viruses. We examine a collection of 50 human, 46 wastewater, 28 bat, and 17 avian archived specimens using 3 published pan-CoV PCR assays called Q-, W-, and X-CoV PCR, to compare the performance of each assay against four CoV genera. X-CoV PCR can detect all four CoV genera, but Q- and W-CoV PCR failed to detect δ-CoV. In total, 21 (42.0%), 9 (18.0%), and 21 (42.0%) of 50 human specimens and 30 (65.22%), 6 (13.04%), and 27 (58.70%) of 46 wastewater specimens were detected using Q-, W-, and X-CoV PCR assays, respectively. The X-CoV PCR assay has a comparable sensitivity to Q-CoV PCR in bat CoV detection. Combining Q- and X-CoV PCR assays can increase sensitivity and avoid false negative results in the early detection of novel CoVs.
A Metagenomic Investigation of Potential Health Risks and Element Cycling Functions of Bacteria and Viruses in Wastewater Treatment Plants
Authors: Zhao Haozhe , Yang Mingfei , Fan Xiang , Gui Qian , Yi Hao , Tong Yigang , Xiao Wei
Published: March 2024

The concentration of viruses in sewage sludge is significantly higher (10–1000-fold) than that found in natural environments, posing a potential risk for human and animal health. However, the composition of these viruses and their role in the transfer of pathogenic factors, as well as their role in the carbon, nitrogen, and phosphorus cycles remain poorly understood. In this study, we employed a shotgun metagenomic approach to investigate the pathogenic bacteria and viral composition and function in two wastewater treatment plants located on a campus. Our analysis revealed the presence of 1334 amplicon sequence variants (ASVs) across six sludge samples, with 242 ASVs (41.22% of total reads) identified as pathogenic bacteria. Arcobacter was found to be the most dominant pathogen accounting for 6.79% of total reads. The virome analysis identified 613 viral genera with Aorunvirus being the most abundant genus at 41.85%. Approximately 0.66% of these viruses were associated with human and animal diseases. More than 60% of the virome consisted of lytic phages. Host prediction analysis revealed that the phages primarily infected Lactobacillus (37.11%), Streptococcus (21.11%), and Staphylococcus (7.11%). Furthermore, our investigation revealed an abundance of auxiliary metabolic genes (AMGs) involved in carbon, nitrogen, and phosphorus cycling within the virome. We also detected a total of 113 antibiotic resistance genes (ARGs), covering major classes of antibiotics across all samples analyzed. Additionally, our findings indicated the presence of virulence factors including the clpP gene accounting for approximately 4.78%, along with toxin genes such as the RecT gene representing approximately 73.48% of all detected virulence factors and toxin genes among all samples analyzed. This study expands our understanding regarding both pathogenic bacteria and viruses present within sewage sludge while providing valuable insights into their ecological functions.
Development of a Mouse-Adapted Reporter SARS-CoV-2 as a Tool for Two-Photon In Vivo Imaging
Authors: Ueki Hiroshi , Kiso Maki , Furusawa Yuri , Iida Shun , Yamayoshi Seiya , Nakajima Noriko , Imai Masaki , Suzuki Tadaki , Kawaoka Yoshihiro
Published: March 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often causes severe viral pneumonia. Although many studies using mouse models have examined the pathogenicity of SARS-CoV-2, COVID-19 pathogenesis remains poorly understood. In vivo imaging analysis using two-photon excitation microscopy (TPEM) is useful for elucidating the pathology of COVID-19, providing pathological insights that are not available from conventional histological analysis. However, there is no reporter SARS-CoV-2 that demonstrates pathogenicity in C57BL/6 mice and emits sufficient light intensity for two-photon in vivo imaging. Here, we generated a mouse-adapted strain of SARS-CoV-2 (named MASCV2-p25) and demonstrated its efficient replication in the lungs of C57BL/6 mice, causing fatal pneumonia. Histopathologic analysis revealed the severe inflammation and infiltration of immune cells in the lungs of MASCV2-p25-infected C57BL/6 mice, not unlike that observed in COVID-19 patients with severe pneumonia. Subsequently, we generated a mouse-adapted reporter SARS-CoV-2 (named MASCV-Venus-p9) by inserting the fluorescent protein-encoding gene Venus into MASCV2-p25 and sequential lung-to-lung passages in C57BL/6 mice. C57BL/6 mice infected with MASCV2-Venus-p9 exhibited severe pneumonia. In addition, the TPEM of the lungs of the infected C57BL/6J mice showed that the infected cells emitted sufficient levels of fluorescence for easy observation. These findings suggest that MASCV2-Venus-p9 will be useful for two-photon in vivo imaging studies of the pathogenesis of severe COVID-19 pneumonia.
Molecular Epidemiology and Clinical Characteristics of an Outbreak on Respiratory Virus Coinfection in Gansu, China
Authors: Liu Wu , Zhang Hui , Zhao Tianshuo , Cai Xianming , Yang Liguo , Gao Genxia , Che Xiaoyan , Zhu Zhenhong , Zeng Tongxia , Cui Fuqiang
Published: March 2024

This study aims to analyze the epidemiological and pathogenic characteristics of an outbreak primarily caused by respiratory syncytial virus (RSV), human rhinovirus (HRV), and human metapneumovirus (HMPV) in a kindergarten and primary school. The outbreak was investigated by field epidemiological investigation, and the common respiratory pathogens were screened by RT-PCR detection technology. The attack rate of this outbreak was 63.95% (110/172). Main symptoms included cough (85.45%), sore throat (60.91%), and sneezing (60.00%). Multifactorial logistic regression analysis revealed that continuous handwashing and mouth and nose covering when sneezing were protective factors. All 15 collected throat swab specimens tested positive for viruses, with HMPV as the predominant pathogen (80.00%), followed by HRV (53.33%), and two cases of positive respiratory syncytial virus (13.33%). Among them, six samples showed coinfections of HMPV and HRV, and one had coinfections of HMPV and RSV, resulting in a coinfection rate of 46.67%. Genetic sequencing indicated that the HMPV genotype in this outbreak was A2c, and the HRV genotype was type A, resulting in a coinfection outbreak of HMPV, HRV, and RSV in schools and kindergartens, suggesting that multi-pathogen surveillance of respiratory tract infections should be strengthened.
Isolation, Identification, and Pathogenicity of a Goose Astrovirus Genotype 1 Strain in Goslings in China
Authors: Wei Feng , He Dalin , Wu Bingrong , Diao Youxiang , Tang Yi
Published: March 2024

Goose astrovirus genotype 1 (GAstV-1) has emerged in goose farms in some provinces of China in recent years and is considered to be one of the pathogens of gout in goslings in China. However, few studies have been conducted on the dynamic distribution, tissue tropism, and pathogenesis of GAstV-1 in goslings. In 2022, an epidemiological investigation of goose astrovirus (GAstV) in goslings was conducted in seven provinces of China. During the investigation, a GAstV-1 designated as GAstV-JSXZ was identified in the kidney of an 8-day-old gosling and was successfully isolated from a goose embryo. The full genome sequence of GAstV-JSXZ was determined using the next-generation sequencing technique. The complete genome of GAstV-JSXZ was 7299-nt-long. Interestingly, the phylogenetic analysis revealed that Chinese GAstV-1 has formed two distinct subgroups based on the ORF 2 genomes, designated GAstV-1 1a and GAstV-1 1b. The GAstV-JSXZ shared the highest identity with GAstV-1 1a strain FLX and TZ03 in nucleotides (ORF1a: 98.3–98.4%; ORF1b: 92.3–99.1%; ORF2: 95.8–98.8%) and amino acid sequences (ORF1a: 99.4–99.5%; ORF1b: 98.2–98.8%; ORF2: 97.0–99.4%). To evaluate the pathogenicity of GAstV-1, 1-day-old goslings were inoculated with the virus by oral and subcutaneous injection routes, respectively. The results revealed that the virus causes extensive pathological organ damage, especially in the kidney, liver, and thymus. Virus-specific genomic RNA could be detected in the cloacal swabs and tissues of infected goslings throughout the experiment. The viral copy numbers examined in the kidney and intestine were the highest, followed by the liver and spleen. These results are likely to provide a new understanding of the pathogenicity of GAstV-1 in geese.
Mechanisms and Cardiorenal Complications of Chronic Anemia in People with HIV
Authors: Kamvuma Kingsley , Hamooya Benson M. , Munsaka Sody , Masenga Sepiso K. , Kirabo Annet
Published: March 2024

Chronic anemia is more prevalent in people living with HIV (PLWH) compared to the general population. The mechanisms that drive chronic anemia in HIV are multifaceted and include functional impairment of hematopoietic stem cells, dysregulation of erythropoietin production, and persistent immune activation. Chronic inflammation from HIV infection adversely affects erythropoiesis, erythrocyte lifespan, and erythropoietin response, leading to a heightened risk of co-infections such as tuberculosis, persistent severe anemia, and increased mortality. Additionally, chronic anemia exacerbates the progression of HIV-associated nephrotoxicity and contributes to cardiovascular risk through immune activation and inflammation. This review highlights the cardinal role of chronic inflammation as a link connecting persistent anemia and cardiovascular complications in PLWH, emphasizing the need for a universal understanding of these interconnected pathways for targeted interventions.
Development and Application of a Duplex RT-RPA Assay for the Simultaneous Detection of Cymbidium mosaic virus and Odontoglossum ringspot virus
Authors: Sun Aiqing , Wang Lihua , Zhang Yiping , Yang Xiumei , Su Yan , Wu Xuewei
Published: March 2024

Cymbidium mosaic virus (CymMV) and Odontoglossum ringspot virus (ORSV) are among the world’s most serious and widespread orchid viruses; they often infect orchids, causing devastating losses to the orchid industry. Therefore, it is critical to establish a method that can rapidly and accurately detect viruses in the field using simple instruments, which will largely reduce the further spread of viruses and improve the quality of the orchid industry and is suitable for mass promotion and application at grassroots agrotechnical service points. In this investigation, we established a rapid amplification method for virus detection at 39 °C for 35 min to detect the presence of CymMV and ORSV simultaneously, sensitively, and specifically in orchids. Primers for the capsid protein (CP)-encoding genes of both viruses were designed and screened, and the reaction conditions were optimized. The experimental amplification process was completed in just 35 min at 39 °C. There were no instances of nonspecific amplification observed when nine other viruses were present. The RPA approach had detection limits of 104 and 103 copies for pMD19T-CymMV and pMD19T-ORSV, respectively. Moreover, the duplex RT-RPA investigation confirmed sensitivity and accuracy via a comparison of detection results from 20 field samples with those of a gene chip. This study presents a precise and reliable detection method for CymMV and ORSV using RT-RPA. The results demonstrate the potential of this method for rapid virus detection. It is evident that this method could have practical applications in virus detection processes.
The mRNA Vaccine Expressing Single and Fused Structural Proteins of Porcine Reproductive and Respiratory Syndrome Induces Strong Cellular and Humoral Immune Responses in BalB/C Mice
Authors: Zhou Luoyi , Wubshet Ashenafi Kiros , Zhang Jiangrong , Hou Shitong , Yao Kaishen , Zhao Qiuyi , Dai Junfei , Liu Yongsheng , Ding Yaozhong , Zhang Jie , Sun Yuefeng
Published: March 2024

PRRS is a viral disease that profoundly impacts the global swine industry, causing significant economic losses. The development of a novel and effective vaccine is crucial to halt the rapid transmission of this virus. There have been several vaccination attempts against PRRSV using both traditional and alternative vaccine design development approaches. Unfortunately, there is no currently available vaccine that can completely control this disease. Thus, our study aimed to develop an mRNA vaccine using the antigens expressed by single or fused PRRSV structural proteins. In this study, the nucleotide sequence of the immunogenic mRNA was determined by considering the antigenicity of structural proteins and the stability of spatial structure. Purified GP5 protein served as the detection antigen in the immunological evaluation. Furthermore, cellular mRNA expression was detected by immunofluorescence and western blotting. In a mice experiment, the Ab titer in serum and the activation of spleen lymphocytes triggered by the antigen were detected by ELISA and ICS, respectively. Our findings demonstrated that both mRNA vaccines can significantly stimulate cellular and humoral immune responses. More specifically, the GP5-mRNA exhibited an immunological response that was similar to that of the commercially available vaccine when administered in high doses. To conclude, our vaccine may show promising results against the wild-type virus in a natural host.
The Biodistribution of Replication-Defective Simian Adenovirus 1 Vector in a Mouse Model
Authors: Chen Juan , Guo Xiaojuan , Zou Xiaohui , Wang Min , Yang Chunlei , Hou Wenzhe , Sprindzuk Matvey V. , Lu Zhuozhuang
Published: March 2024

The administration route affects the biodistribution of a gene transfer vector and the expression of a transgene. A simian adenovirus 1 vector carrying firefly luciferase and GFP reporter genes (SAdV1-GFluc) were constructed, and its biodistribution was investigated in a mouse model by bioluminescence imaging and virus DNA tracking with real-time PCR. Luciferase activity and virus DNA were mainly found in the liver and spleen after the intravenous administration of SAdV1-GFluc. The results of flow cytometry illustrated that macrophages in the liver and spleen as well as hepatocytes were the target cells. Repeated inoculation was noneffective because of the stimulated serum neutralizing antibodies (NAbs) against SAdV-1. A transient, local expression of low-level luciferase was detected after intragastric administration, and the administration could be repeated without compromising the expression of the reporter gene. Intranasal administration led to a moderate, constant expression of a transgene in the whole respiratory tract and could be repeated one more time without a significant increase in the NAb titer. An immunohistochemistry assay showed that respiratory epithelial cells and macrophages in the lungs were transduced. High luciferase activity was restricted at the injection site and sustained for a week after intramuscular administration. A compromised transgene expression was observed after a repeated injection. When these mice were intramuscularly injected for a third time with the human adenovirus 5 (HAdV-5) vector carrying a luciferase gene, the luciferase activity recovered and reached the initial level, suggesting that the sequential use of SAdV-1 and HAdV-5 vectors was practicable. In short, the intranasal inoculation or intramuscular injection may be the preferred administration routes for the novel SAdV-1 vector in vaccine development.
Calcium Chloride as a Novel Stabilizer for Foot-and-Mouth Disease Virus and Its Application in the Vaccine Formulation
Authors: Jin Jong Sook , Lee Gyeongmin , Kim Jae Young , Lee SooAh , Park Jong-Hyeon , Park Sun Young , Ko Young-Joon
Published: March 2024

The thermal stability of the in-house-developed foot-and-mouth disease (FMD) type O and A viruses was evaluated, and the O Jincheon virus was found to exhibit the lowest thermal stability. To overcome this instability, we proposed a novel stabilizer, calcium chloride. The thermal stability of FMDVs increased up to a CaCl2 concentration of 10 mM, and it had a decreasing trend at >30 mM. The O Jincheon virus showed a significant decrease in the amount of antigen over time at 4 °C. In contrast, the samples treated with CaCl2 showed stable preservation of the virus without significant antigen loss. After the CaCl2-formulated vaccine was administered twice to pigs, the virus neutralization titer reached approximately 1:1000, suggesting that the vaccine could protect pigs against the FMDV challenge. In summary, the O Jincheon virus is difficult to utilize as a vaccine given its low stability during storage after antigen production. However, following its treatment with CaCl2, it can be easily utilized as a vaccine. This study evaluated CaCl2 as a novel stabilizer in FMD vaccines and may contribute to the development of stable vaccine formulations, especially for inherently unstable FMDV strains.
Genistein Alleviates Intestinal Oxidative Stress by Activating the Nrf2 Signaling Pathway in IPEC-J2 Cells
Authors: Li Yanpin , Cai Long , Bi Qingyue , Sun Wenjuan , Pi Yu , Jiang Xianren , Li Xilong
Published: March 2024

In the weaning period, piglets often face oxidative stress, which will cause increased diarrhea and mortality. Genistein, a flavonoid, which is extracted from leguminous plants, possesses anti-inflammatory and antioxidative bioactivities. However, little is known about whether genistein could attenuate the oxidative stress that occurs in porcine intestinal epithelial cells (IPEC-J2). Herein, this experiment was carried out to investigate the protective effects of genistein in the IPEC-J2 cells oxidative stress model. Our results disclosed that H2O2 stimulation brought about a significant diminution in catalase (CAT) activity and cell viability, as well as an increase in the levels of reactive oxygen species (ROS) in IPEC-J2 cells (p < 0.05), whereas pretreating cells with genistein before H2O2 exposure helped to alleviate the reduction in CAT activity and cell viability (p < 0.05) and the raise in the levels of ROS (p = 0.061) caused by H2O2. Furthermore, H2O2 stimulation of IPEC-J2 cells remarkably suppressed gene level Nrf2 and CAT expression, in addition to protein level Nrf2 expression, but pretreating cells with genistein reversed this change (p < 0.05). Moreover, genistein pretreatment prevented the downregulation of occludin expression at the gene and protein level, and ZO-1 expression at gene level (p < 0.05). In summary, our findings indicate that genistein possesses an antioxidant capacity in IPEC-J2 cells which is effective against oxidative stress; the potential mechanism may involve the Nrf2 signaling pathway. Our findings could offer a novel nutritional intervention strategy to enhance the intestinal health of piglets during the weaning process.
Effects of Beraprost with or without NOS Inhibition on Plasma Aldosterone and Hemodynamics in Healthy Cats
Authors: Matsuura Takumi , Yoshimura Aritada , Fukushima Ryuji
Published: March 2024

Objectives: The aim of the study was to evaluate the hemodynamic and RA system effects of the oral administration of the clinical dose of beraprost for feline CKD in healthy cats, and also to examine whether NOS inhibition reversed them. Methods: A placebo-controlled pharmacological sequential design study was carried out to assess the plasma aldosterone and renin concentrations (PAC and PRC), blood pressure, heart rate, and exploratorily to estimate renal plasma flow (RPF) and renal vascular resistance (RVR) with simplified methods. Results: Beraprost reduced PAC when compared to the placebo (p < 0.05); this was reversed when NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was added to the beraprost treatment (p < 0.01). No differences in the PRC or hemodynamic parameters were detected between beraprost and the placebo. The correlation ratios (η2) showed opposite relationships between beraprost and the added L-NAME effects on PAC, mean blood pressure (MBP), heart rate, estimated RPF (p < 0.001), estimated RVR (p < 0.01), and PRC (p < 0.05). Conclusions: In healthy cats, the clinical dose of beraprost suppresses PAC, which can be reversed by the inhibition of NOS.
The Alleviating Effect of Taxifolin on Deoxynivalenol-Induced Damage in Porcine Intestinal Epithelial Cells
Authors: Zhu Min , Fang Yongxia , Cheng Yujie , Xu E , Zhang Yiyu , Zhai Zhenya
Published: March 2024

Deoxynivalenol (DON) contamination in feed is a global concern that severely threatens the health of animals and humans. Taxifolin (TA) is a natural flavonoid, a member of the polyphenols, that possesses robust antioxidant properties. This study aimed to investigate the effect of TA on DON-induced damage in porcine intestinal epithelial cells (IPEC-J2). The cells were pre-incubated with a series of concentrations of TA for 24 h and exposed to DON (0.5 μg/mL) for another 24 h. The results showed that pretreatment with TA (150 μM) significantly inhibited the DON-induced decline in cell viability (p < 0.05) and cell proliferation (p < 0.01). Additionally, 150 μM TA also alleviated DON-induced apoptosis (p < 0.01). Moreover, TA decreased the production of reactive oxygen species (ROS) induced by DON (p < 0.01). In addition, TA attenuated DON-induced cell junction damage (p < 0.05). Further experiments showed that TA reversed the DON-induced reduction in antioxidant capacity in the IPEC-J2 cells, probably via activating the Nrf2 signaling pathway (p < 0.05). Collectively, these findings suggest that 150 μM TA can protect against 0.5 μg/mL DON-induced damage to IPEC-J2 cells, potentially via the activation of the Nrf2 signaling pathway. This study provides insight into TA’s potential to act as a green feed additive in the pig farming industry and its efficacy in counteracting DON-induced intestinal damage.