bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of aged garlic and ginkgo biloba extracts on the pharmacokinetics of sofosbuvir in rats
Authors: Wasef Abanoub K. , Wahdan Sara A. , Saeed Noha M. , El‐Demerdash Ebtehal
Published: August 2022

Sofosbuvir is a direct acting antiviral (DAA) approved for the treatment of hepatitis C virus (HCV). Sofosbuvir is a substrate of P‐glycoprotein (P‐gp). For this reason, inhibitors, or inducers of intestinal P‐gp may alter the plasma concentration of sofosbuvir and increase or decrease its efficacy causing a significant change in its pharmacokinetic parameters. The purpose of the study was to evaluate the pharmacokinetic interaction between either aged garlic or ginkgo biloba extracts with sofosbuvir through targeting P‐gp as well as possible toxicities in rats. Rats were divided into four groups and treated for 14 days with saline, verapamil (15 mg/kg, PO), aged garlic extract (120 mg/kg, PO), or ginkgo biloba extract (25 mg/kg, PO) followed by a single oral dose of sofosbuvir (40 mg/kg). Validated LC‐MS/MS was used to determine sofosbuvir and its metabolite GS‐331007 in rat plasma. Aged garlic extract caused a significant decrease of sofosbuvir AUC(0−t) by 36%, while ginkgo biloba extract caused a significant increase of sofosbuvir AUC(0−t) by 11%. Ginkgo biloba extract exhibited a significant increase of the sofosbuvir t1/2 by 60%, while aged garlic extract significantly increased the clearance of sofosbuvir by 63%. The pharmacokinetic parameters of GS‐331007 were not affected. The inhibitory action of ginkgo biloba on P‐gp and the subsequent increase in the sofosbuvir plasma concentration did not show a significant risk of renal or hepatic toxicity. Conversely, although aged garlic extracts increased intestinal P‐gp expression, they did not alter the Cmax and Tmax of sofosbuvir and did not induce significant hepatic or renal toxicities.
Ink‐printed metal/graphene aerogel for glucose electro‐oxidation
Authors: Tsang Alpha Chi Him , Hui Kwun Nam , Hui Kwan San , Liu Biyuan , Yu Leyi , Shi Bin , Huang Haibao
Published: August 2022

Three‐dimensional (3D) printing has become one of the promising technologies for the development of bulk‐sized nanomaterial composites for electrocatalysis. However, traditional methods such as field deposition modeling and stereolithography are not suitable for the development of functionalized materials for practical use. A large number of studies have focused on the development of the direct ink writing (DIW) printing technique for the fabrication of graphene aerogel (GA)‐based electrodes with binders for electrocatalysis. Only a few studies have focused on the synthesis of GA materials from binder‐free graphene oxide (GO) using the DIW 3D printing method. Here, we describe the preparation of GA‐based electrodes (without size contraction) with different Pd–Pt loadings using the DIW printing method with a commercial 3D food printer. The electron microscopy results showed that a Pd–Pt/GA monolith with a high Pd–Pt loading (59.43 wt%) could be obtained. The DIW‐printed Pd–Pt/GA‐2 electrode showed good electrochemical performance in glucose electrooxidation (GOR), with a high output current density of 0.94 A g−1 in 0.3 M glucose/1 M NaOH solution at the 3000th cycle operation (60 h). This study shows the potential of DIW‐printed binder‐free Pd–Pt/GA electrodes for use in fuel cell applications.
Tropaeline O‐oxalic acid‐benzalkonium chloride photogalvanic cells for solar energy conversion and storage
Authors: Koli Pooran , Kumar Rajendra , Dayma Yashodhara , Pareek Ramesh K. , Meena Anita , Jonwal Meenakshi
Published: August 2022

The photogalvanic (PG) cells involve a change in the electrode potential by photochemical processes along with the diffusion of ionic species through the bulk electrolyte. The PG cells have used so far the complex H‐shaped cell design, heavy sensitizer molecules with low diffusivity, and low photo‐stability. All these factors are not conducive to the fabrication of cheap cells with good electrical output. To address all these concerns, the tropaeline‐O dye photosensitizer (a low molecular weight molecule with higher diffusion and higher photo‐stability) has been exploited with diffusion‐friendly low cost and a simple transparent cylindrical glass tube. The optimum values of the cell's electrical parameters are:  potential 998 mV, current 3200 µA, and power 829.5 µW, and it is quite similar at all illumination window sizes.
A non‐metabolic function of hexokinase 2 in small cell lung cancer: promotes cancer cell stemness by increasing USP11‐mediated CD133 stability
Authors: Wang Juhong , Shao Fei , Yang Yannan , Wang Wei , Yang Xueying , Li Renda , Cheng Hong , Sun Sijin , Feng Xiaoli , Gao Yibo , He Jie , Lu Zhimin
Published: August 2022

Background

Maintenance of cancer stem‐like cell (CSC) stemness supported by aberrantly regulated cancer cell metabolism is critical for CSC self‐renewal and tumor progression. As a key glycolytic enzyme, hexokinase 2 (HK2) plays an instrumental role in aerobic glycolysis and tumor progression. However, whether HK2 directly contribute to CSC stemness maintenance in small cell lung cancer (SCLC) is largely unclear. In this study, we aimed to investgate whether HK2 independent of its glycolytic activity is directly involved in stemness maintenance of CSC in SCLC.

Methods

Immunoblotting analyses were conducted to determine the expression of HK2 in SCLC CSCs and their differentiated counterparts. CSC‐like properties and tumorigenesis of SCLC cells with or without HK2 depletion or overexpression were examined by sphere formation assay and xenograft mouse model. Immunoprecipitation and mass spectrometry analyses were performed to identify the binding proteins of CD133. The expression levels of CD133‐associated and CSC‐relevant proteins were evaluated by immunoblotting, immunoprecipitation, immunofluorescence, and immunohistochemistry assay. RNA expression levels of Nanog, POU5F1, Lin28, HK2, Prominin‐1 were analyzed through quantitative reverse transcription PCR. Polyubiquitination of CD133 was examined by in vitro or in vivo ubiquitination assay. CD133+ cells were sorted by flow cytometry using an anti‐CD133 antibody.

Results

We demonstrated that HK2 expression was much higher in CSCs of SCLC than in their differentiated counterparts. HK2 depletion inhibited CSC stemness and promoted CSC differentiation. Mechanistically, non‐mitochondrial HK2 directly interacted with CD133 and enhanced CD133 expression without affecting CD133 mRNA levels. The interaction of HK2 and CD133 promoted the binding of the deubiquitinase ubiquitin‐specific protease 11 (USP11) to CD133, thereby inhibiting CD133 polyubiquitylation and degradation. HK2‐mediated upregulation of CD133 expression enhanced the expression of cell renewal regulators, SCLC cell stemness, and tumor growth in mice. In addition, HK2 expression was positively correlated with CD133 expression in human SCLC specimens, and their expression levels were associated with poor prognosis of SCLC patients.

Conclusions

These results revealed a critical non‐metabolic function of HK2 in promotion of cancer cell stemness. Our findings provided new insights into the multifaceted roles of HK2 in tumor development.
Association between cannabis use with urological cancers: A population‐based cohort study and a mendelian randomization study in the UK biobank
Authors: Huang Jingyi , Huang Da , Ruan Xiaohao , Huang Jinlun , Xu Danfeng , Heavey Susan , Olivier Jonathan , Na Rong
Published: August 2022

Background

Legislation of cannabis use has been approved in many European and North American countries. Its impact on urological cancers is unclear. This study was conducted to explore the association between cannabis use and the risk of urological cancers.

Methods

We identified 151,945 individuals with information on cannabis use in the UK Biobank from 2006 to 2010. Crude and age‐standardized incidence ratios of different urological cancers were evaluated in the entire cohort and subgroups. Cox regression was performed for survival analysis.

Results

Previous use of cannabis was a significant protective factor for renal cell carcinoma (HR = 0.61, 95%CI:0.40–0.93, p = 0.021) and prostate cancer (HR = 0.82, 95%CI:0.73–0.93, p = 0.002) in multivariable analysis. The association between previous cannabis use and both renal cell carcinoma and bladder cancer was only observed in females (HRRCC = 0.42, 95%CI:0.19–0.94, p = 0.034; HRBCa = 0.43, 95%CI:0.21–0.86, p = 0.018) but not in men. There was no significant association between cannabis use and testicular cancer incidence. Mendelian randomization demonstrated a potential causal effect of cannabis use on a lower incidence of renal cell carcinoma.

Conclusions

Previous use of cannabis was associated with a lower risk of bladder cancer, renal cell carcinoma, and prostate cancer. The inverse association between cannabis and both renal cell carcinoma and bladder cancer was only found in females but not in males.
Bioactive Secondary Metabolites Isolated from the Antarctic Lichen Himantormia lugubris
Authors: Hyung Koo Man , Shin Min‐Ji , Ju Kim Min , Lee Seulah , Eun So Jae , Hee Kim Ji , Hyuck Lee Jun , Suh Sung‐Suk , Joung Youn Ui
Published: August 2022

Two new depsidones, himantormiones A and B (1 and 2) were isolated and identified from the Antarctic lichen, Himantormia lugubris (Parmeliaceae), with seven known compounds (3–9). The structures of two new compounds (1 and 2) were determined by means of spectroscopic analyses, including 1D and 2D NMR and HR‐MS. The isolated compounds were tested for antimicrobial and cytotoxic activities, where himantormione B (2) exhibited inhibitory effect against Staphylococcus aureus with the IC50 value of 7.01±0.85 mM. Compound 2 also exhibited strong cytotoxic activity against HCT116 cells (colon cancer) with the EC50 value of 1.11±0.85 μM, where that of the positive control, 5‐fluouracil, was 9.4±1.90 μM.
Spain−France Special Collection: Current Trends in Electrochemistry
Authors: Sirés Ignasi , Rodrigo Manuel A. , Gomez‐Mingot Maria , Roberts Edward P. L.
Published: August 2022

The Meeting of the Electrochemistry Group of the Spanish Royal Society of Chemistry (RSEQ) is an annual event that has taken place since the late 1970s. The meeting brings together the entire Spanish electrochemistry community at a single event to discuss the latest advances in our field, and normally takes place in different Spanish cities. Over the last decade, mainly due to the deep economic crisis experienced in Spain, the number of electrochemists trained in Spain who have emigrated and today lead important groups in other European countries and in the USA has grown significantly. Thus, the XLI Meeting of the Electrochemistry Group was organized in Paris (France) in 2021, and served to regroup all electrochemists trained in Spain, both emigrants and residents. By holding the meeting outside of Spain, the Electrochemistry Group aimed to internationalize the group‘s meetings and to strengthen collaborations with the French electrochemistry community.
Synthesis of 2‐Acetamido‐1,3,4‐Tri‐O‐Acetyl‐2‐Deoxy‐D‐Mannopyranose ‐6‐Phosphate Prodrugs as Potential Therapeutic Agents
Authors: Pertusati Fabrizio , Morewood James
Published: August 2022

Sugar phosphates are emerging as potential therapeutic candidates for certain diseases. However, their high polarity makes them poorly absorbed by the body and their penetration inside the cell is even more difficult without a proper transporter. Amino sugar phosphates (n‐amino‐n‐deoxy‐sugars, carbohydrates in which a hydroxyl group has been replaced with an amine group), such as N‐acetyl‐D‐mannosamine (ManNac)‐6‐phosphate have shown potential as a treatment for a muscular disease called GNE myopathy caused by a deficiency in the production of sialic acid. However, its high polarity leads to poor absorption and consequent high dosage in humans, causing unwanted side effects. Herein, we describe the application of phosphoramidate prodrug chemistry to 1,3,4‐O‐acetylated N‐acetylmannosamine (Ac3ManNAc) to deliver ManNAc‐6‐phosphate (ManNAc‐6‐P), a critical intermediate in sialic acid biosynthesis. Sialic acid deficiency is a hallmark of GNE myopathy, a rare congenital disorder of glycosylation (CDG), caused by mutations in the gene “GNE,” that limit the production of ManNAc‐6‐P. Synthetic methods were developed to provide a library of Ac3ManNAc‐6‐phosphoramidates that were evaluated in a series of studies for their potential as a treatment for GNE myopathy. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Synthesis of 2‐Acetamido‐1,3,4‐tri‐O‐acetyl‐2‐deoxy‐D‐mannopyranose.

Basic Protocol 2: Preparation of 3‐acetamido‐6‐((((((S)‐1‐ethoxy‐4‐methyl‐1‐oxo‐pentan‐2‐yl) amino) (phenoxy)phosphoryl) oxy) methyl) tetrahydro‐2H‐pyran‐2,4,5‐triyl triacetate (5).

Support Protocol: Preparation of ethyl (chloro(phenoxy)phosphoryl)‐l‐leucinate.
Lower photosynthetic rate and photosynthetic nitrogen use efficiency in northern Japanese soybean cultivars than Midwestern U.S. cultivars
Authors: Kumagai Etsushi , Hasegawa Toshihiro
Published: August 2022

In major soybean‐producing regions such as the United States, farm yield has increased in recent years. This gain is accompanied by genetic improvements in net photosynthetic rate (PN). However, farm yields in Japan remain low and unchanged, suggesting a lack of progress in improving yield and the underlying PN through recent breeding. It is unclear how much Japanese breeders have improved PN, or whether the PN of Japanese cultivars is inferior to cultivars from the United States and, if so, which physiological traits should be improved to increase PN in Japanese cultivars. To answer these questions, we compared PN and related physiological traits of cultivars released during the past 60 yr in the Tohoku region of northern Japan (JP group) with those of cultivars from the Midwestern United States (U.S. group). In the U.S. group, PN increased with year of release at both flowering and the beginning of seed filling (respectively, R2 and R5) stages, and was accompanied by an increase in leaf N content by area (Narea). This demonstrates improved PN resulting from recent breeding. In contrast, there was no difference in PN between old and new cultivars in the JP group, indicating that PN was not improved by breeding. PN at R5 in the JP group was lower than in the U.S. group and was associated with lower stomatal conductance in the JP group. Narea at R5 was higher in the JP group than in the U.S. group and was associated with lower photosynthetic N use efficiency in the JP group.
A need for assurance: Do internal control systems integrate environmental, social, and governance factors?
Authors: Harasheh Murad , Provasi Roberta
Published: August 2022

In the article, we provide an original linkage between the corporate environmental, social, and governance (ESG) rating and the cost of internal control system (ICSC) stemmed from two closely related frameworks: the 2017 CoSO Framework, which calls to strengthen internal control systems to integrate ESG issues, and the EU directive on nonfinancial reporting (2014/95/EU) that entered into force in 2017. Thus, we evaluate both introductions showing ESG integration in the internal control activities. We cover firms listed on Milan Exchange from 2016 to 2019, providing a thorough analysis with robustness tests. The findings imply that firms should consider both ESG rating and the internal control system cost as strategic corporate tools for value enhancement; therefore, companies should allocate the resources appropriately to internal control activities to incorporate ESG issues and create value since internal control provides the first assurance for ESG integration. The limitations of this study pave the way for further research directions; incorporating the new amendment of the EU directive on nonfinancial disclosure, allowing for a better valuation creation assessment; and whether there is a substitution between sustainability performance and other corporate issues such as taxes and marketing expenditure.
Improving knowledge on genotoxicity dynamics in somatic and germ cells of crayfish (Procambarus clarkii)
Authors: Marçal Raquel , Marques Ana Margarida , Pacheco Mário , Guilherme Sofia
Published: August 2022

The harmful effects of pesticides can be extended beyond the exposure time scale. Appraisals combining exposure and long‐term post‐exposure periods appear as an unavoidable approach in pesticide risk assessment, thus allowing a better understanding of the real impact of agrochemicals in non‐target organisms. This study aimed to evaluate the progression of genetic damage in somatic and germ tissues of the crayfish Procambarus clarkii, also seeking for gender‐specificities, following exposure (7 days) to penoxsulam (23 μg L−1) and a post‐exposure (70 days) period. The same approach was applied to the model genotoxicant ethyl methanesulfonate (EMS; 5 mg L−1) as a complementary mean to improve knowledge on genotoxicity dynamics (induction vs. recovery). Penoxsulam induced DNA damage in all tested tissues, disclosing tissue‐ and gender‐specificities, where females showed to be more vulnerable than males in the gills, while males demonstrated higher susceptibility in what concerns internal organs, that is, hepatopancreas and gonad. Crayfish were unable to recover from the DNA damage induced by EMS in gills and hepatopancreas (both genders) as well as in spermatozoa. The genotoxicity in the hepatopancreas was only perceptible in the post‐exposure period. Oxidative DNA lesions were identified in hepatopancreas and spermatozoa of EMS‐exposed crayfish. The spermatozoa proved to be the most vulnerable cell type. It became clear that the characterization of the genotoxic hazard of a given agent must integrate a complete set of information, addressing different types of DNA damage, tissue‐ and gender‐specificities, as well as a long‐term appraisal of temporal progression of damage.
Detection of Lithium‐Ion Cells’ Degradation through Deconvolution of Electrochemical Impedance Spectroscopy with Distribution of Relaxation Time
Authors: Iurilli Pietro , Brivio Claudio , Wood Vanessa
Published: August 2022

Herein, a methodology to investigate aging of commercial cylindrical Li‐ion cells is introduced. Distribution of relaxation time (DRT) method is applied to deconvolute electrochemical impedance spectroscopy (EIS) measurements and separate those polarization effects that are usually overlapped in the frequency domain by means of a peak‐based representation. Half‐cells are built at the beginning and end of life to link the electrochemical and aging processes occurring at anode and/or the cathode sides. Moreover, lab‐made full‐cells are exploited to verify the reproducibility when compared with cylindrical cells. The results of an extensive analysis of around 500 EIS spectra return an unambiguous attribution of different electrochemical processes to different time constants and ultimately to different DRT peaks. Digital imaging validates graphite degradation, mainly related to lithium plating. Scanning electron microscopy validates the degradation at NMC cathode, mainly attributed to particle cracking. It is concluded that DRT peaks allow to characterize cell aging and their tracking can help to develop more reliable state of health estimators.
Nonlinear backstepping hierarchical control of shake table using high‐gain observer
Authors: Xiao Yifei , Pan Xiao , Yang Tony T.Y.
Published: August 2022

Shake table testing is a common technique used to examine the responses of structures under dynamic loads. Shake table is often regulated using linear controller, such as proportional‐integral‐derivative (PID) controller. However, traditional PID control cannot consider inherent nonlinearities in the structural and control systems. In this paper, a series of novel backstepping control methods, which consider the nonlinearities in the structural and control systems, have been developed. In addition, high‐gain observers, which can provide highly accurate estimation of the shake table displacement, velocity and acceleration, are also developed. The proposed backstepping control methods and high‐gain observers are implemented in a hierarchical framework, where the high‐level backstepping controller generates the command signal for the low‐level controller to execute. A total of four hierarchical backstepping control methods, including the acceleration‐based backstepping hierarchical control (ABHC), the ABHC with high‐gain observer (ABHCO), the displacement‐based backstepping hierarchical control (DBHC) and the DBHC with high‐gain observer (DBHCO), have been implemented. Detailed parameter studies have been conducted to identify the optimized parameters for the proposed hierarchical backstepping control methods. The proposed control method is verified through a series of shake table tests. The experimental results show the ABHC, ABHCO, DBHC and DBHCO can all achieve high‐performance shake table control, especially with superior acceleration tracking over the traditional PID control. Overall, ABHCO achieves the best tracking performance for displacement, velocity and acceleration.
Effect of Land Cover on Ecoregion-Scale Spatial Patterns of Mercury Contamination of Largemouth Bass in the Southeastern United States
Authors: Drenner Ray W. , Chumchal Matthew M. , Adams Kimberly J. , Seymour Ryan D.
Published: August 2022

Consumption of methylmercury (MeHg)-contaminated fish is the primary source of MeHg in humans and poses a hazard to human health. Because of widespread atmospheric deposition of inorganic mercury (IHg), all water bodies in the United States have been contaminated with Hg. In aquatic ecosystems, IHg is converted to MeHg, which biomagnifies, reaching high concentrations in piscivorous fish. It is not possible for governmental agencies to monitor fish from every waterbody to determine if concentrations of MeHg in fish are hazardous to human health. To help government agencies focus their monitoring efforts, it is critical that we develop the ability to predict regions where waterbodies are most likely to contain fish with hazardous concentrations of MeHg. The objective of the present study was to examine the relationship between MeHg contamination of largemouth bass (Micropterus salmoides), a popular piscivorous gamefish, and land cover in 24 ecoregions across 15 states in the southeastern United States. In our study we demonstrate for the first time that 72% of the variance in average concentrations of MeHg in largemouth bass between ecoregions of the southeastern United States can be explained by the percentage coverage by evergreen forests, emergent herbaceous wetlands, and pasture/hay. Land cover determines the sensitivity of freshwater systems to atmospheric IHg deposition, and the present study suggests that at the ecoregion scale, MeHg bioaccumulation in piscivorous gamefish, and ultimately the health hazard that these MeHg-contaminated fish pose to humans, can be in part predicted by land-cover type. Environ Toxicol Chem 2022;41:2386–2394. © 2022 SETAC
Elevated Mercury Concentrations and Isotope Signatures (N, C, Hg) in Yellowfin Tuna (Thunnus albacares) from the Galápagos Marine Reserve and Waters off Ecuador
Authors: Muñoz-Abril Laia , Valle Carlos A. , Alava Juan José , Janssen Sarah E. , Sunderland Elsie M. , Rubianes-Landázuri Francisco , Emslie Steven D.
Published: August 2022

We examined how dietary factors recorded by C and N influence Hg uptake in 347 individuals of yellowfin tuna (Thunnus albacares), an important subsistence resource from the Galápagos Marine Reserve (Ecuador) and the Ecuadorian mainland coast in 2015–2016. We found no differences in total Hg (THg) measured in red muscle between the two regions and no seasonal differences, likely due to the age of the fish and slow elimination rates of Hg. Our THg concentrations are comparable to those of other studies in the Pacific (0.20-9.60 mg/kg wet wt), but a subset of individuals exhibited the highest Hg concentrations yet reported in yellowfin tuna. Mercury isotope values differed between Δ199Hg and δ202Hg in both regions (Δ199Hg = 2.86 ± 0.04‰ vs. Δ199Hg = 2.33 ± 0.07‰), likely related to shifting food webs and differing photochemical processing of Hg prior to entry into the food web. There were significantly lower values of both δ15N and δ13C in tuna from Galápagos Marine Reserve (δ15N: 8.5–14.2‰, δ13C: −18.5 to −16.1‰) compared with those from the Ecuadorian mainland coast (δ15N: 8.3–14.4‰, δ13C: −19.4 to −11.9‰), of which δ13C values suggest spatially constrained movements of tuna. Results from the pooled analysis, without considering region, indicated that variations in δ13C and δ15N values tracked changes of Hg stable isotopes. Our data indicate that the individual tuna we used were resident fish of each region and were heavily influenced by upwellings related to the eastern Pacific oxygen minimum zone and the Humboldt Current System. The isotopes C, N, and Hg reflect foraging behavior mainly on epipelagic prey in shallow waters and that food web shifts drive Hg variations between these populations of tuna. Environ Toxicol Chem 2022;41:2732–2744. © 2022 SETAC
Hepatic Transcriptomic Responses to Ethinylestradiol in Two Life Stages of Japanese Quail
Authors: Jeon Yeon-Seon , Crump Doug , Boulanger Emily , Soufan Othman , Park Bradley , Basu Niladri , Hecker Markus , Xia Jianguo , Head Jessica A.
Published: August 2022

Chemical risk assessment for avian species typically depends on information from toxicity tests performed in adult birds. Early-life stage (ELS) toxicity tests have been proposed as an alternative, but incorporation of these data into existing frameworks will require knowledge about the similarities/differences between ELS and adult responses. The present study uses transcriptomics to assess hepatic gene expression in ELS and adult Japanese quail following exposure to ethinylestradiol (EE2). Prior to incubation, ELS quail were dosed with measured EE2 concentrations of 0.54, 6.3, and 54.2 µg/g egg weight via air cell injection. Adult quail were fed a single dose of EE2 at nominal concentrations of 0, 0.5, and 5 mg/kg body weight by gavage. Liver tissue was collected from five to six individuals per dose group at mid-incubation for ELS quail and 4 days after dosing for adults. A total of 283 and 111 differentially expressed genes (DEGs) were detected in ELS and adult quail, respectively, 16 of which were shared across life stages. Shared DEGs included estrogenic biomarkers such as vitellogenin genes and apovitellenin-1. For the dose groups that resulted in the highest number of DEGs (ELS, 6.3 µg/g; adult, 5 mg/kg), 21 and 35 Kyoto Encyclopedia of Genes and Genomes pathways were enriched, respectively. Ten of these pathways were shared between life stages, including pathways involved with signaling molecules and interaction and the endocrine system. Taken together, our results suggest conserved mechanisms of action following estrogenic exposure across two life stages, with evidence from differential expression of key biomarker genes and enriched pathways. The present study contributes to the development and evaluation of ELS tests and toxicogenomic approaches and highlights their combined potential for screening estrogenic chemicals. Environ Toxicol Chem 2022;41:2769–2781. © 2022 SETAC
A Novel Approach to Developing Thresholds for Total Dissolved Solids Using Standardized and Experimental Toxicity Test Methods
Authors: Brent Robert N. , Kunkel Jared , Tomek Zachary , Buchardt Dalton , DeLisle Peter F. , Sivers Sarah
Published: August 2022

The increasing salinization of freshwater streams from anthropogenic land uses and activities is a growing global environmental problem. Increases in individual ions (such as sodium or chloride) and combined measures such as total dissolved solids (TDS) threaten drinking water supplies, agricultural and economic interests, and the ecological health of freshwater streams. Because the toxicity of high ionic strength waters depends on the specific ion composition, few water quality standards exist to protect freshwater streams from salinization. In the present study, we used a novel approach to develop site-specific and ecologically relevant TDS thresholds for the protection of aquatic life. The first step of the approach was to characterize the ion composition of the waterbody or region of interest and prepare artificial samples to match that composition. Using a combination of standardized toxicity test species and more ecologically relevant field-collected species, toxicity tests were then conducted on these artificial samples prepared at a range of TDS concentrations. The advantage of this approach is that water quality criteria can be developed for easy-to-measure generalized parameters such as TDS while ensuring that the criteria are protective of instream aquatic life and account for the complex interactions of the various ions contributing to salinization. We tested this approach in Sand Branch, Loudoun County, Virginia, USA, where salinization from hard rock mining and urban runoff has impaired aquatic life. Acute and chronic TDS thresholds of 938 and 463 mg/L, respectively, were developed in this stream and used for total maximum daily load development in the watershed. The approach provides a potential model for establishing protective thresholds for other waterbodies impacted by salinization. Environ Toxicol Chem 2022;41:2782–2796. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Linking evolutionary potential to extinction risk: applications and future directions
Authors: Forester Brenna R , Beever Erik A , Darst Catherine , Szymanski Jennifer , Funk W Chris
Published: August 2022

Extinction‐risk assessments play a major role in prioritizing conservation action at national and international levels. However, quantifying extinction risk is challenging, especially when including the full suite of adaptive responses to environmental change. In particular, evolutionary potential (EP) – the capacity to evolve genetically based changes that increase fitness under changing conditions – has proven difficult to evaluate, limiting its inclusion in risk assessments. Theory, experiments, simulations, and field studies all highlight the importance of EP in characterizing and mitigating extinction risk. Disregarding EP can therefore result in ineffective allocation of resources and inadequate recovery planning. Fortunately, proxies for EP can be estimated from environmental, phenotypic, and genetic data. Some proxies can be incorporated into quantitative extinction‐risk assessments, whereas others better inform basic conservation actions that maximize resilience to future change. Integration of EP into conservation decision making is challenging but essential and remains an important issue for innovation in applied conservation science.

Front Ecol Environ 2022;
Basin modelling and source rock characteristics of the Late Palaeoproterozoic Cuizhuang Formation in the Yuncheng sub‐basin, North China: Implications for hydrocarbon generation and expulsion history
Authors: Khaled Ahmed , Li Rongxi , Xi Shengli , Yu Qiang , Wu Xiaoli , Zhao Bangsheng , Zhang Yanni , Zhao Di
Published: August 2022

The present investigation is the first to provide information on the formation, process and influence factors for hydrocarbon generation and expulsion potential of the Cuizhuang Formation source rock in the Yuncheng sub‐basin to decipher the reason why no commercial petroleum resources have been found so far. In this study, data from the Jitan‐1 well in the Yuncheng sub‐basin were applied for the Cuizhuang Formation source rock basin modelling and organic geochemical analyses to reconstruct the burial and thermal evolution history and reveal the timing and process of hydrocarbon generation and expulsion. The modelling results indicate that the peak palaeotemperature of the Cuizhuang Formation source rock reached ~205°C in the Middle Carboniferous (~327 Ma) at a maximum burial depth of ~4000 m, when rapid burial subsidence and thermal events played a significant role in increasing thermal maturity. The Cuizhuang Formation generated and expelled small amounts of hydrocarbons from the Early Ordovician until the Middle Carboniferous, starting with the primary kerogen cracking and conversion to oil from the Early to Middle Ordovician (~476–461 Ma), corresponding to the thermal maturity values of 0.55–0.70 %VRo and transformation ratio (TR) <10%. The expulsion of most generated oil (0.70–1.30 %VRo, TR of 10%–90%) started from the Middle Ordovician to the Early Carboniferous (~461–351 Ma), before reaching the secondary cracking of the retained oil into gas (>1.30 %VRo and TR of 90%–100%) from the Early to Middle Carboniferous (~351–327 Ma). Destruction of the initial formation of hydrocarbon reservoirs in the Yuncheng sub‐basin was primarily controlled by the Middle Carboniferous tectonic event with its major uplift‐erosion, resulting in the absence of potential hydrocarbon reservoirs in recent exploration activities in some parts of the Yuncheng sub‐basin.
Addressing disaster and health risks for sustainable outer space
Authors: Harris Myles , Duda Patrizia I. , Kelman Ilan , Glick Navonel
Published: August 2022

Any future outer space exploration and exploitation should more fully consider disaster and health risks as part of aiming for sustainability. The advent of the so-called “New Space” race, age, or era characterized by democratization, commercialization, militarization, and overlapping outer space activities such as tourism presents challenges for disaster-related and health-related risks in and for outer space. Such challenges have been extensively researched for earth, but less so for space. This article presents an overview of key aspects for addressing disaster and health risks in outer space within a wider sustainability framing. After an introduction providing background and scope, this article's next section considers some key health and disaster risks within sustainable outer space and offers insights from earth. The following two sections apply this knowledge by focusing on how analogue missions and international legal and voluntary regimes can each be used to reduce risks and potentially make outer space healthier and safer. The findings advocate that there is a wealth of knowledge and experience about mitigating risks to health and disaster risk reduction on earth that can inform spaceflight and exploration. The examples explored include the physical, legal, and regulatory aspects of the “New Space” industry, which highlights the relevance of equating examples on earth. The article concludes that expectations must be managed regarding scenarios for which response, rescue, and recovery are precluded, prompting a necessary focus on prevention and risk reduction. In doing so, earth-based scenarios and aspects of the so-called “Old Space” offer useful insights and should be examined further for “New Space.” Integr Environ Assess Manag 2023;19:994–1001. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Missense mutations in spike protein of SARS‐CoV‐2 delta variant contribute to the alteration in viral structure and interaction with hACE2 receptor
Authors: Mahmood Tousif Bin , Hossan Mohammad Imran , Mahmud Shafi , Shimu Mst. Sharmin Sultana , Alam Md. Jahidul , Bhuyan Md. Mahfuzur Rahman , Emran Talha Bin
Published: August 2022

Introduction

Many of the global pandemics threaten human existence over the decades among which coronavirus disease (COVID‐19) is the newest exposure circulating worldwide. The RNA encoded severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus is referred as the pivotal agent of this deadly disease that induces respiratory tract infection by interacting host ACE2 receptor with its spike glycoprotein. Rapidly evolving nature of this virus modified into new variants helps in perpetrating immune escape and protection against host defense mechanism. Consequently, a new isolate, delta variant originated from India is spreading perilously at a higher infection rate.

Methods

In this study, we focused to understand the conformational and functional significance of the missense mutations found in the spike glycoprotein of SARS‐CoV‐2 delta variant performing different computational analysis.

Results

From physiochemical analysis, we found that the acidic isoelectric point of the virus elevated to basic pH level due to the mutations. The targeted mutations were also found to change the interactive bonding pattern and conformational stability analyzed by the molecular dynamic's simulation. The molecular docking study also revealed that L452R and T478K mutations found in the RBD domain of delta variant spike protein contributed to alter interaction with the host ACE2 receptor.

Conclusions

Overall, this study provided insightful evidence to understand the morphological and attributive impact of the mutations on SARS‐CoV‐2 delta variant.
Parecoxib sodium alleviates ischemia reperfusion‐induced pulmonary injury via inhibiting ERK/NF‐κB and further activating the HIF‐1α pathway
Authors: Guo Jiantao , Yang Yiping
Published: August 2022

Introduction

The lungs are extremely vulnerable to ischemia/reperfusion (I/R), which is characterized by intense inflammation, oxidative stress, alveolar damage, and vascular permeability. Parecoxib sodium (Pare) has been shown to exert protective effects against multiple I/R‐induced tissue injuries. However, its role in I/R‐induced lung injury remains unknown. This study aimed to reveal the roles and mechanisms of Pare in pulmonary I/R injury.

Methods

Sixty‐six rats were randomly divided into three groups: The sham‐operated group, the pulmonary I/R group, and the Pare‐pretreated I/R group. Pare at 10 mg/kg or saline (vehicle control) were intraperitoneally administered to rats once per day for 5 consecutive days before ischemia. Serum and tissue samples were harvested following 2 h of reperfusion. The oxygenation index (OI) and alveolar‐arterial oxygen partial pressure difference (PA‐aO2) were analyzed. The levels or activities of malondialdehyde, superoxidase dismutase, catalase, glutathione peroxidase, intracellular reactive oxygen species, tumor necrosis factor‐α, interleukin (IL)‐6, and IL‐8 were examined. The mitochondrial membrane potential was measured. The protein expression levels of the extracellular signal‐regulated kinase (ERK), nuclear factor‐κB (NF‐κB) and their phosphorylated forms, and hypoxia‐inducible factor‐1α (HIF‐1α) were detected. Histological changes were observed using hematoxylin and eosin staining. Moreover, the survival rate following pulmonary I/R injury was recorded daily.

Results

Pare significantly increased the OI, decreased the PA‐aO2, increased the levels of antioxidants, while decreasing the levels of oxidants, and alleviated mitochondrial dysfunction and the histopathological damage induced by I/R. Furthermore, Pare inhibited the expression of proinflammatory cytokines, suppressed the activation of ERK and NF‐κB, further increased HIF‐1α expression, and significantly improved the rat survival rate.

Conclusions

Pare pretreatment attenuated lung I/R injury by inhibiting oxidative stress and the inflammatory response possibly via inhibiting the activation of the ERK/NF‐κB pathway and further activating the HIF‐1α pathway.
C–C chemokine receptor 5 and acute graft‐versus‐host disease
Authors: Yuan Jing , Ren Han‐yun
Published: August 2022

Background

The C–C chemokine receptor 5 (CCR5) is mainly expressed in a variety of immune cells. It interacts with multiple chemokine ligands that mediate the trafficking and recruitment of effector cells toward sites of inflammation. CCR5 not only plays a critical role in cell growth, activation, differentiation, adhesion, and migration but also participates in the development of acute graft‐versus‐host disease (GVHD) after allogeneic hematopoietic cell transplantation.

Methods

This is a literature review article. The research design method is an evidence‐based rapid review. The present discourse aim is first to scrutinize and assess the available literature on CCR5 and acute GVHD. Standard literature and database searches were implemented, gathered relevant material, and extracted information was then assessed.

Results

CCR5 is a marker of GVHD effector cells, and CCR5 expression is elevated when acute GVHD occurs. CCR5 blockade with maraviroc in clinical trials results in a low incidence of acute GVHD. The immune mechanism includes that CCR5 blockade inhibits donor T cell migration and recruitment toward target organs, reduces the absolute numbers of donor T cells, is capable of slightly suppressing dendritic cell maturation, and reduces the percentage of Th1 and Th17 subsets. CCR5 blockade also inhibits internalization and activation of chemokines, inhibits proliferation and chemotaxis of T cells, and decreases the production of TNF‐α and IFN‐γ. In addition, there may be a form of crosstalk between CCR5 and CCR2. Inconsistently, infusion of CCR5−/− Tregs into lethally irradiated mice significantly increased the infiltration of CD4+ and CD8+ T cells into the liver, resulting in earlier and more severe GVHD.

Conclusion

This review indicates that CCR5 plays an important role in pathogenesis and development of acute GVHD. Elucidating its role in different immune cells will aid the development of targeted therapeutic treatments.
Broadband spectral verification of optical clearing reversibility in lung tissue
Authors: Oliveira Luís R. , Ferreira Ricardo M. , Pinheiro Maria R. , Silva Hugo F. , Tuchin Valery V. , Oliveira Luís M.
Published: August 2022

The increase of tissue transparency through sequential optical immersion clearing treatments and treatment reversibility have high interest for clinical applications. To evaluate the clearing reversibility in a broad spectral range and the magnitude of the transparency created by a second treatment, the present study consisted on measuring the spectral collimated transmittance of lung tissues during a sequence of two treatments with electronic cigarette (e‐cig) fluid, which was intercalated with an immersion in saline. The saline immersion clearly reverted the clearing effect in the lung tissue in the spectral range between 220 and 1000 nm. By a later application of a second treatment with the e‐cig fluid, the magnitude of the optical clearing effect was observed to be about the double as the one observed in the first treatment, showing that the molecules of the optical clearing agent might have converted some bound water into mobile water during the first treatment.
Constructional fear treatment: Teaching fearful shelter dogs to approach and interact with a novel person
Authors: Katz Morgan , Rosales‐Ruiz Jesús
Published: August 2022

Of the millions of dogs that enter animal shelters in the United States each year, many exhibit behaviors labeled as fear, which can decrease their likelihood of adoption. Current dog training procedures to treat these behaviors can take months or even years to show significant change. When these procedures are used in shelters, they mainly focus on reducing fear, as opposed to teaching specific behaviors to increase adoptions. The goal of the current study was to teach fearful shelter dogs to interact with a novel person. A seven‐step shaping procedure used the removal of the novel person as a reinforcer. The dogs learned a series of behaviors, starting with looking at the person and small head movements and progressing until the dog was approaching the front of the kennel and voluntarily interacting with the person. All three dogs completed the program in a short amount of time (under 40 min) and showed an increase in approaching the front of the kennel, sniffing, tail wagging, and accepting petting. These behaviors persisted during a return‐to‐baseline condition, suggesting that the newly shaped behaviors had come under the control of positive reinforcement in the form of social interaction with the experimenter.
Diagnostic utility of lung echography for congestive heart failure performed by junior resident doctors
Authors: Nagaharu Keiki , Tsumura Natsumi , Itoh Toshiyuki , Murata Tetsuya
Published: August 2022

Background

Dyspnea is a high priority symptom in the emergency department, with heart failure (HF) as one of its leading causes. Recently, the “comet tail sign (CTS),” a pulmonary ultrasonographic sign, has been proposed as an efficacious tool for detecting pulmonary edema. However, to the best of our knowledge, there have been no published data regarding its utility when performed by non‐experts, including junior residents.

Methods

Between September 2017 and December 2018, patients with dyspnea, who were admitted to the ER, were enrolled. CTS was evaluated by junior residents at the ER. All patients were evaluated by cardiologists independently, and clinical HF was defined as requiring pharmacological intervention by a cardiologist. At the end of this study, we investigated the results of CTS, laboratory data, and available radiological images.

Results

A total of 95 patients were enrolled in the current study, wherein 42 patients were treated by cardiologists as those with clinical HF. Our results showed that CTS could identify clinical HF with a sensitivity of 71.4% and a specificity of 81.1%. The sensitivity of CTS against brain natriuretic peptide (BNP) (cut‐off value, 100 pg/ml) was calculated at 92.5%. Furthermore, when evaluated together with peripheral edema, CTS identified clinical HF with a sensitivity of 96%. False positives for CTS included bilateral pneumonia, hypoalbuminemia, and interstitial pneumonitis.

Conclusions

Our results indicate that CTS is a simple and effective tool for the use of non‐experts, including junior residents.
The Development of Normal Fetal External Genitalia Throughout Gestation
Authors: Pinson Kelsey , Melber Dora J , Nguyen Ngoc‐Hieu , Montaney Laura , Basu Reshmi , Mims Joseph , Pretorius Dolores , Lamale‐Smith Leah
Published: August 2022

In this review, we describe normal development of fetal genitalia throughout gestation as well as the identification of normal male and female genitalia on ultrasound. We use abnormal and ambiguous genitalia as illustrative tools to assist with the identification of normal genitalia and recognition of some of the most common abnormalities in external genitalia development.
Interference With Implanted Upper Airway Stimulation Device by Phones With Magnet Technology
Authors: Plawecki Andrea , Tripathi Nitika , Tovar Torres Maria , Yaremchuk Kathleen
Published: August 2022

Newer iPhone models with MagSafe magnetic technology can cause electromagnetic interference with the Inspire upper airway stimulator device (a surgical implant for the treatment of obstructive sleep apnea). Laryngoscope, 132:2513–2515, 2022
Dipole Formation at Active Materials/P(NDI3N‐T‐Br) Interface in Organic‐Based Photovoltaic
Authors: Alghamdi Amira R. , Bjuggren Jonas M. , Pan Xun , Andersson Mats R. , Andersson Gunther G.
Published: August 2022

In this work, a new potential electron transport material, poly[(N,N'‐bis(3‐(N,N‐dimethyl)‐N‐ethylammonium)propyl)naphthalene‐1,4,5,8‐bis(dicarboximide)‐2,6‐diyl)‐alt‐2,5‐thiophene)]dibromide P(NDI3N‐T‐Br), is studied in conjunction with active layers formed by poly[2,3‐bis(3‐octyloxyphenyl)quinoxaline‐5,8‐diyl‐alt‐thiophene‐2,5‐diyl] (TQ1) and poly[[N,N′‐bis(2‐octyldodecyl)‐naphthalene‐1,4,5,8‐bis(dicarboximide)‐2,6‐diyl]‐alt‐5,5′‐(2,2′‐bithiophene)] (N2200). The energy levels of the active layer TQ1 and N2200 in contact with P(NDI3N‐T‐Br) have been determined by photoelectron spectroscopy. The dipole formed at the interface of the active layer and P(NDI3N‐T‐Br) is significantly different to the dipole formed at the respective interface with ITO. The dipole between the active layer and P(NDI3N‐T‐Br) blocks the transfer of holes from TQ1 to P(NDI3N‐T‐Br) which is desired, but the hole still transfers from the N2200 to P(NDI3N‐T‐Br) due to N2200 being an electron acceptor. This energy level alignment meets the expectation of using P(NDI3N‐T‐Br) as an interface layer in blocking the hole transfer to the interface layer when TQ1:N2200 is used in the active layer. The present work provides an understanding of P(NDI3N‐T‐Br) as charge extraction layer and indicates its potential to be used in organic photovoltaics.