bluuebunny/crossref_metadata_2025 huggingface dataset:
Catecholamine Surges Cause Cardiomyocyte Necroptosis via a RIPK1–RIPK3-Dependent Pathway in Mice
Authors: Wu Penglong , Cai Mingqi , Liu Jinbao , Wang Xuejun
Published: September 2021

Background: Catecholamine surges and resultant excessive β-adrenergic stimulation occur in a broad spectrum of diseases. Excessive β-adrenergic stimulation causes cardiomyocyte necrosis, but the underlying mechanism remains obscure. Necroptosis, a major form of regulated necrosis mediated by RIPK3-centered pathways, is implicated in heart failure; however, it remains unknown whether excessive β-adrenergic stimulation-induced cardiac injury involves necroptosis. Hence, we conducted the present study to address these critical gaps.

Methods and Results: Two consecutive daily injections of isoproterenol (ISO; 85 mg/kg, s.c.) or saline were administered to adult mixed-sex mice. At 24 h after the second ISO injection, cardiac area with Evans blue dye (EBD) uptake and myocardial protein levels of CD45, RIPK1, Ser166-phosphorylated RIPK1, RIPK3, and Ser345-phosphorylated MLKL (p-MLKL) were significantly greater, while Ser321-phosphorylated RIPK1 was significantly lower, in the ISO-treated than in saline-treated wild-type (WT) mice. The ISO-induced increase of EBD uptake was markedly less in RIPK3−/− mice compared with WT mice (p = 0.016). Pretreatment with the RIPK1-selective inhibitor necrostatin-1 diminished ISO-induced increases in RIPK3 and p-MLKL in WT mice and significantly attenuated ISO-induced increases of EBD uptake in WT but not RIPK3−/− mice.

Conclusions: A large proportion of cardiomyocyte necrosis induced by excessive β-adrenergic stimulation belongs to necroptosis and is mediated by a RIPK1–RIPK3-dependent pathway, identifying RIPK1 and RIPK3 as potential therapeutic targets for catecholamine surges.
Parasitic Load Correlates With Left Ventricular Dysfunction in Patients With Chronic Chagas Cardiomyopathy
Authors: de Oliveira Maykon Tavares , Schmidt André , da Silva Maria Cláudia , Donadi Eduardo Antônio , da Silva João Santana , Marin-Neto José Antônio
Published: September 2021

Background: Chronic Chagas disease (CChD), one of the infectious parasitic diseases with the greatest social and economic impact upon a large part of the American continent, has distinct clinical manifestations in humans (cardiac, digestive, or mixed clinical forms). The mechanisms underlying the development of the most common and ominous clinical form, the chronic Chagas cardiomyopathy (CCC) have not been completely elucidated, despite the fact that a high intensity of parasite persistence in the myocardium is deemed responsible for an untoward evolution of the disease. The present study aimed to assess the parasite load CCC and its relation to left ventricular ejection fraction (LVEF), a definite prognostic marker in patients with CCC.

Methods: Patients with CCC were clinically evaluated using 12-lead-electrocardiogram, echocardiogram, chest X-ray. Peripheral blood sampling (5 ml of venous blood in guanidine/EDTA) was collected from each patient for subsequent DNA extraction and the quantification of the parasite load using real-time PCR.

Results: One-hundred and eighty-one patients with CCC were evaluated. A total of 140 (77.3%) had preserved left ventricular ejection fraction (of ≥40%), and 41 individuals had LV dysfunction (LVEF of <40%). A wide variation in parasite load was observed with a, mean of 1.3460 ± 2.0593 (0.01 to 12.3830) par. Eq./mL. The mean ± SD of the parasite load was 0.6768 ± 0.9874 par. Eq./mL and 3.6312 ± 2.9414 par. Eq./mL in the patients with LVEF ≥ 40% and <40%, respectively.

Conclusion: The blood parasite load is highly variable and seems to be directly related to the reduction of LVEF, an important prognostic factor in CCC patients.
Developing a Validity Argument for an Inference-Making and Reasoning Measure for Use in Higher Education
Authors: Fechter Tia , Dai Ting , Cromley Jennifer G. , Nelson Frank E. , Van Boekel Martin , Du Yang
Published: September 2021

The Inference-Making and Reasoning in Biology (IMRB) measure is an assessment tool intended to 1) aid university personnel in advising students on course enrollment, 2) identify students in need of interventions to increase their reasoning skills and likelihood of completing STEM majors, 3) support instructors in determining growth in students’ reasoning skills, and 4) provide a measuring tool to gauge success of higher-education interventions intended to increase reasoning skills. Validity arguments for these four uses of the IMRB are provided by implementing a validity argument approach. This work exemplifies the advantages of framing validation studies within a validity argument framework.
Long-Term Glycemic Variability Is Associated With Arterial Stiffness in Chinese Adults
Authors: Zhang Yuwen , Wu Shujing , Li Mian , Wang Tiange , Xu Min , Lu Jieli , Wang Shuangyuan , Zhang Jie , Bi Yufang , Wang Weiqing , Ning Guang , Xu Yu , Chen Yuhong
Published: September 2021

Objective

The aim of the study was to investigate the association between the visit-to-visit variability (VVV) of fasting plasma glucose (FPG) and arterial stiffness in Chinese adults.

Methods

We performed a cohort study involving 2002 Chinese adults with no history of myocardial infarction or stroke. All the participants attended three visits (the baseline visit in 2008, the 2nd visit in 2009 and the 3rd visit in 2013). We used four measures to define the VVV of FPG across the three visits: the standard deviation (SD), the coefficient of variation (CV), the average successive variability (ASV) and the variability independent of the mean (VIM). We used brachial-ankle pulse wave velocity (ba-PWV) to measure arterial stiffness at the 2nd and the 3rd visits.

Results

Compared with the lowest tertile of all the four measurements of VVV of FPG, significantly increased levels of ba-PWV change, ratio of ba-PWV change and the occurrence of the elevated ba-PWV were found in the highest tertile. The odds ratio (OR) and 95% confidence interval (CI) comparing participants in the highest tertile vs. the lowest tertile of FPG-SD was 1.37 (1.01-1.86) for risks of having elevated ba-PWV, even after adjustment for covariates including the mean FPG. Similar results were found for FPG-CV and FPG-VIM.

Conclusion

Greater long-term variability of FPG was associated with an increased risk of arterial stiffness, suggesting that the VVV of FPG could be used for an early detection of subclinical atherosclerosis.
Does the Anti-Mullerian Hormone Decline Rate Improve the Prediction of Age at Menopause?
Authors: Ramezani Tehrani Fahimeh , Sheidaei Ali , Firouzi Faezeh , Tohidi Maryam , Azizi Fereidoun , Behboudi-Gandevani Samira
Published: September 2021

Objectives

There are controversial studies investigating whether multiple anti-Mullerian hormone (AMH) measurements can improve the individualized prediction of age at menopause in the general population. This study aimed to reexplore the additive role of the AMH decline rate in single AMH measurement for improving the prediction of age at physiological menopause, based on two common statistical models for analysis of time-to-event data, including time-dependent Cox regression and Cox proportional-hazards regression models.

Methods

A total of 901 eligible women, aged 18–50 years, were recruited from the Tehran Lipid and Glucose Study (TLGS) population and followed up every 3 years for 18 years. The serum AMH level was measured at the time of recruitment and twice after recruitment within 6-year intervals using the Gen II AMH assay. The added value of repeated AMH measurements for the prediction of age at menopause was explored using two different statistical approaches. In the first approach, a time-dependent Cox model was plotted, with all three AMH measurements as time-varying predictors and the baseline age and logarithm of annual AMH decline as time-invariant predictors. In the second approach, a Cox proportional-hazards model was fitted to the baseline data, and improvement of the complex model, which included repeated AMH measurements and the logarithm of the AMH annual decline rate, was assessed using the C-statistic.

Results

The time-dependent Cox model showed that each unit increase in the AMH level could reduce the risk of menopause by 87%. The Cox proportional-hazards model also improved the prediction of age at menopause by 3%, according to the C-statistic. The subgroup analysis for the prediction of early menopause revealed that the risk of early menopause increased by 10.8 with each unit increase in the AMH annual decline rate.

Conclusion

This study confirmed that multiple AMH measurements could improve the individual predictions of the risk of at physiological menopause compared to single AMH measurements. Different alternative statistical approaches can also offer the same interpretations if the essential assumptions are met.
Study on Waste Heat-Driven Refrigeration System for Energy Saving and Fast Cooling of Dust Collector in Monocrystalline Silicon Manufacture
Authors: Hou Jiwei , Xu Yingjie
Published: September 2021

Single-crystal silicon is key raw material in photovoltaic industry. In its manufacture, silicon monoxide dust, a byproduct, is collected under vacuum environment. To clean the dust collector, air is recharged into the collector, reacting with the dust and causing very high temperature. Collector components may be damaged. It also takes several hours to cool down. In this paper, a cooling system based on ejection refrigeration cycle is proposed, which collects the reaction heat and simultaneously controls the collector temperature around 100°C. Then, it is driven by stored waste reaction heat and cools down the dust to a lower temperature. The designed cooling system, employing a 9.7972 m2 fin-tube heat exchanger, can simultaneously meet the cooling load of four dust collectors with 330L/S capacity. By a thermodynamic model established in this work, performance analysis is carried out. Generating temperature around 73°C and evaporating temperature around 6°C are recommended for system operation. Results also show the cooling system is able to provide 3270 kJ cooling energy that is needed by the collector, for fast cooling down the dust no longer than 620 s. It is about 92% shorter than the time of current collector, indicating the cooling system is effective and feasible.
Snow Cover and Snow Persistence Changes in the Mocho-Choshuenco Volcano (Southern Chile) Derived From 35 Years of Landsat Satellite Images
Authors: Chávez Roberto O. , Briceño Verónica F. , Lastra José A. , Harris-Pascal Daniel , Estay Sergio A.
Published: September 2021

Mountain regions have experienced above-average warming in the 20th century and this trend is likely to continue. These accelerated temperature changes in alpine areas are causing reduced snowfall and changes in the timing of snowfall and melt. Snow is a critical component of alpine areas - it drives hibernation of animals, determines the length of the growing season for plants and the soil microbial composition. Thus, changes in snow patterns in mountain areas can have serious ecological consequences. Here we use 35 years of Landsat satellite images to study snow changes in the Mocho-Choshuenco Volcano in the Southern Andes of Chile. Landsat images have 30 m pixel resolution and a revisit period of 16 days. We calculated the total snow area in cloud-free Landsat scenes and the snow frequency per pixel, here called “snow persistence” for different periods and seasons. Permanent snow cover in summer was stable over a period of 30 years and decreased below 20 km2 from 2014 onward at middle elevations (1,530–2,000 m a.s.l.). This is confirmed by negative changes in snow persistence detected at the pixel level, concentrated in this altitudinal belt in summer and also in autumn. In winter and spring, negative changes in snow persistence are concentrated at lower elevations (1,200–1,530 m a.s.l.). Considering the snow persistence of the 1984–1990 period as a reference, the last period (2015–2019) is experiencing a −5.75 km2 reduction of permanent snow area (snow persistence > 95%) in summer, −8.75 km2 in autumn, −42.40 km2 in winter, and −18.23 km2 in spring. While permanent snow at the high elevational belt (>2,000 m a.s.l.) has not changed through the years, snow that used to be permanent in the middle elevational belt has become seasonal. In this study, we use a probabilistic snow persistence approach for identifying areas of snow reduction and potential changes in alpine vegetation. This approach permits a more efficient use of remote sensing data, increasing by three times the amount of usable scenes by including images with spatial gaps. Furthermore, we explore some ecological questions regarding alpine ecosystems that this method may help address in a global warming scenario.
Simplified Communities of Seed-Dispersers Limit the Composition and Flow of Seeds in Edge Habitats
Authors: Razafindratsima Onja H. , Raoelinjanakolona Nasandratra Nancia , Heriniaina Rio R. , Nantenaina Rindra H. , Ratolojanahary Tianasoa H. , Dunham Amy E.
Published: September 2021

Edge effects, driven by human modification of landscapes, can have critical impacts on ecological processes such as species interactions, with cascading impacts on biodiversity as a whole. Characterizing how edges affect vital biotic interactions such as seed dispersal by frugivores is important for better understanding potential mechanisms that drive species coexistence and diversity within a plant community. Here, we investigated how differences between frugivore communities at the forest edge and interior habitats of a diverse tropical rainforest relate to patterns of animal-mediated seed dispersal and early seedling recruitment. We found that the lemur communities across the forest edge-interior gradient in this system showed the highest species richness and variability in body sizes at intermediate distances; the community of birds showed the opposite pattern for species richness. Three large-bodied frugivores, known to be effective dispersers of large seeds, tended to avoid the forest edge. As result, the forest edges received a lower rate of animal-mediated seed dispersal compared to the interior habitats. In addition, we also found that the seeds that were actively dispersed by animals in forest edge habitats were smaller in size than seeds dispersed in the forest interior. This pattern was found despite a similarity in seed size of seasonally fruiting adult trees and shrubs between the two habitats. Despite these differences in dispersal patterns, we did not observe any differences in the rates of seedling recruitment or seed-size distribution of successful recruit species. Our results suggest that a small number of frugivores may act as a potential biotic filter, acting on seed size, for the arrival of certain plant species to edge habitats, but other factors may be more important for driving recruitment patterns, at least in the short term. Further research is needed to better understand the potential long-term impacts of altered dispersal regimes relative to other environmental factors on the successional dynamics of edge communities. Our findings are important for understanding potential ecological drivers of tree community changes in forest edges and have implications for conservation management and restoration of large-seeded tree species in disturbed habitats.
‘Taking Fishers’ Knowledge to the Lab’: An Interdisciplinary Approach to Understand Fish Trophic Relationships in the Brazilian Amazon
Authors: Pereyra Paula Evelyn Rubira , Hallwass Gustavo , Poesch Mark , Silvano Renato Azevedo Matias
Published: September 2021

Trophic levels can be applied to describe the ecological role of organisms in food webs and assess changes in ecosystems. Stable isotopes analysis can assist in the understanding of trophic interactions and use of food resources by aquatic organisms. The local ecological knowledge (LEK) of fishers can be an alternative to advance understanding about fish trophic interactions and to construct aquatic food webs, especially in regions lacking research capacity. The objectives of this study are: to calculate the trophic levels of six fish species important to fishing by combining data from stable isotopes analysis and fishers’ LEK in two clear water rivers (Tapajós and Tocantins) in the Brazilian Amazon; to compare the trophic levels of these fish between the two methods (stable isotopes analysis and LEK) and the two rivers; and to develop diagrams representing the trophic webs of the main fish prey and predators based on fisher’s LEK. The fish species studied were Pescada (Plagioscion squamosissimus), Tucunaré (Cichla pinima), Piranha (Serrasalmus rhombeus), Aracu (Leporinus fasciatus), Charuto (Hemiodus unimaculatus), and Jaraqui (Semaprochilodus spp.). A total of 98 interviews and 63 samples for stable isotopes analysis were carried out in both rivers. The average fish trophic levels did not differ between the stable isotopes analysis and the LEK in the Tapajós, nor in the Tocantins Rivers. The overall trophic level of the studied fish species obtained through the LEK did not differ from data obtained through the stable isotopes analysis in both rivers, except for the Aracu in the Tapajós River. The main food items consumed by the fish according to fishers’ LEK did agree with fish diets as described in the biological literature. Fishers provided useful information on fish predators and feeding habits of endangered species, such as river dolphin and river otter. Collaboration with fishers through LEK studies can be a viable approach to produce reliable data on fish trophic ecology to improve fisheries management and species conservation in tropical freshwater environments and other regions with data limitations.
Bioprospecting Trichoderma: A Systematic Roadmap to Screen Genomes and Natural Products for Biocontrol Applications
Authors: Rush Tomás A. , Shrestha Him K. , Gopalakrishnan Meena Muralikrishnan , Spangler Margaret K. , Ellis J. Christopher , Labbé Jesse L. , Abraham Paul E.
Published: September 2021

Natural products derived from microbes are crucial innovations that would help in reaching sustainability development goals worldwide while achieving bioeconomic growth. Trichoderma species are well-studied model fungal organisms used for their biocontrol properties with great potential to alleviate the use of agrochemicals in agriculture. However, identifying and characterizing effective natural products in novel species or strains as biological control products remains a meticulous process with many known challenges to be navigated. Integration of recent advancements in various “omics” technologies, next generation biodesign, machine learning, and artificial intelligence approaches could greatly advance bioprospecting goals. Herein, we propose a roadmap for assessing the potential impact of already known or newly discovered Trichoderma species for biocontrol applications. By screening publicly available Trichoderma genome sequences, we first highlight the prevalence of putative biosynthetic gene clusters and antimicrobial peptides among genomes as an initial step toward predicting which organisms could increase the diversity of natural products. Next, we discuss high-throughput methods for screening organisms to discover and characterize natural products and how these findings impact both fundamental and applied research fields.
Highlighting the Relevance of CD8+ T Cells in Filarial Infections
Authors: Kwarteng Alexander , Asiedu Ebenezer , Koranteng Kelvin Kwaku , Asiedu Samuel Opoku
Published: September 2021

The T cell immune responses in filarial infections are primarily mediated by CD4+ T cells and type 2-associated cytokines. Emerging evidence indicates that CD8+ T cell responses are important for anti-filarial immunity, however, could be suppressed in co-infections. This review summarizes what we know so far about the activities of CD8+ T cell responses in filarial infections, co-infections, and the associations with the development of filarial pathologies.
A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine
Authors: Jangra Sonia , Landers Jeffrey J. , Rathnasinghe Raveen , O’Konek Jessica J. , Janczak Katarzyna W. , Cascalho Marilia , Kennedy Andrew A. , Tai Andrew W. , Baker James R. , Schotsaert Michael , Wong Pamela T.
Published: September 2021

Several SARS-CoV-2 vaccines have received EUAs, but many issues remain unresolved, including duration of conferred immunity and breadth of cross-protection. Adjuvants that enhance and shape adaptive immune responses that confer broad protection against SARS-CoV-2 variants will be pivotal for long-term protection as drift variants continue to emerge. We developed an intranasal, rationally designed adjuvant integrating a nanoemulsion (NE) that activates TLRs and NLRP3 with an RNA agonist of RIG-I (IVT DI). The combination adjuvant with spike protein antigen elicited robust responses to SARS-CoV-2 in mice, with markedly enhanced TH1-biased cellular responses and high virus-neutralizing antibody titers towards both homologous SARS-CoV-2 and a variant harboring the N501Y mutation shared by B1.1.7, B.1.351 and P.1 variants. Furthermore, passive transfer of vaccination-induced antibodies protected naive mice against heterologous viral challenge. NE/IVT DI enables mucosal vaccination, and has the potential to improve the immune profile of a variety of SARS-CoV-2 vaccine candidates to provide effective cross-protection against future drift variants.
Machine Learning Applications in Solid Organ Transplantation and Related Complications
Authors: Balch Jeremy A. , Delitto Daniel , Tighe Patrick J. , Zarrinpar Ali , Efron Philip A. , Rashidi Parisa , Upchurch Gilbert R. , Bihorac Azra , Loftus Tyler J.
Published: September 2021

The complexity of transplant medicine pushes the boundaries of innate, human reasoning. From networks of immune modulators to dynamic pharmacokinetics to variable postoperative graft survival to equitable allocation of scarce organs, machine learning promises to inform clinical decision making by deciphering prodigious amounts of available data. This paper reviews current research describing how algorithms have the potential to augment clinical practice in solid organ transplantation. We provide a general introduction to different machine learning techniques, describing their strengths, limitations, and barriers to clinical implementation. We summarize emerging evidence that recent advances that allow machine learning algorithms to predict acute post-surgical and long-term outcomes, classify biopsy and radiographic data, augment pharmacologic decision making, and accurately represent the complexity of host immune response. Yet, many of these applications exist in pre-clinical form only, supported primarily by evidence of single-center, retrospective studies. Prospective investigation of these technologies has the potential to unlock the potential of machine learning to augment solid organ transplantation clinical care and health care delivery systems.
Biological CO2 Uptake and Upwelling Regulate the Air-Sea CO2 Flux in the Changjiang Plume Under South Winds in Summer
Authors: Li Dewang , Ni Xiaobo , Wang Kui , Zeng Dingyong , Wang Bin , Jin Haiyan , Li Hongliang , Zhou Feng , Huang Daji , Chen Jianfang
Published: September 2021

The partial pressure of CO2(pCO2) in the sea and the air-sea CO2flux in plume waters are subject to interactions among biological production, horizontal advection, and upwelling under wind events. In this study, time series ofpCO2and other biogeochemical parameters in the dynamic Changjiang plume were presented to illuminate the controlling factors ofpCO2and the air-sea CO2flux after a strong south wind event (July 23–24, maximum of 11.2 ms–1). The surfacepCO2decreased by 310 μatm (to 184 μatm) from July 24 to 26. Low-pCO2waters (<200 μatm) were observed in the following 2 days. Corresponding chlorophyllaand dissolved oxygen (DO) increase, and a significant relationship between DO and npCO2indicated that biological uptake drove thepCO2decrease. The salinity of undersaturated-CO2waters decreased by 3.57 (from 25.03 to 21.46) within 2 days (July 27–28), suggesting the offshore advection of plume waters in which CO2had been biologically reduced. Four days after the wind event, the upwelling of high-CO2waters was observed, which increased thepCO2by 428 μatm (up to 584 μatm) within 6 days. Eight days after the onset of upwelling, the surfacepCO2started to decrease (from 661 to 346 μatm within 3 days), which was probably associated with biological production. Regarding the air-sea CO2flux, the carbon sink of the plume was enhanced as the low-pCO2plume waters were pushed offshore under the south winds. In its initial stage, the subsequent upwelling made the surface waters act as a carbon source to the atmosphere. However, the surface waters became a carbon sink again after a week of upwelling. Such short-term air-sea carbon fluxes driven by wind have likely occurred in other dynamic coastal waters and have probably induced significant uncertainties in flux estimations.
Characterization and Function Analysis of β, β-carotene-9′, 10′-oxygenase 2 (BCDO2) Gene in Carotenoid Metabolism of the Red Shell Hard Clam (Meretrix meretrix)
Authors: Fu Lulu , Shi Heming , Dai Wenfang , Yao Hanhan , Bao Yongbo , Lin Zhihua , Dong Yinghui
Published: September 2021

The relationship between carotenoid and shellfish shell color has gained increasing attention. β, β-carotene-9′,10′-oxygenase 2 (BCDO2) is a key enzyme in animal carotenoid metabolism, and its accumulation affects the change in body color, as demonstrated in mammals, birds, and fish. However, it is unclear whether BCDO2 is involved in the formation of the red shell color of clam. To explore the molecular structure and biological function of BCDO2 gene in the process of carotenoids accumulation, in this study, the BCDO2 from hard clam Meretrix meretrix (designated as Mm-BCDO2) was cloned and characterized, and the single-nucleotide polymorphisms (SNPs) associated with shell color were detected. The results of qRT-PCR indicated that Mm-BCDO2 gene was expressed in all six tested tissues, and the expression of mantle was significantly higher than other tissues (P < 0.05). The association analysis identified 20 SNPs in the exons of Mm-BCDO2, among which three loci (i.e., c.984A > C, c.1148C > T, and c.1187A > T) were remarkably related (P < 0.05) to the shell color of clam. The western blot analysis revealed that the expression level of Mm-BCDO2 in the mantle of red shell clams was stronger than that of white shell clams (P < 0.05). Further, the immunofluorescence analysis indicated that the single-layer columnar cells at the edge of the mantle were the major sites for the Mm-BCDO2 secretion. This study explored the potential impacts of BCDO2 gene on the shell color of M. meretrix, which provided a theoretical basis for a better understanding of the important role of BCDO2 in carotenoid metabolism.
Production and Characterization of Keratin/Tragacanth Gum Nanohydrogels for Drug Delivery in Medical Textiles
Authors: Mansouri Shirazi Nazanin , Eslahi Niloofar , Gholipour-Kanani Adeleh
Published: September 2021

Keratin protein has been applied for biomedical applications due to its biocompatibility, biodegradability, mechanical resistance, and bioavailability. Tragacanth gum (TG) as a polysaccharide-based biopolymer has wound healing and antimicrobial properties. In this study, keratin was extracted from protein-based chicken feather by using reduction hydrolysis (sodium sulfide), and nanogels of keratin and TG composites at different ratios were produced by using the chemical cross-linking method. Then, cinnamon (5 and 10%) as an antibacterial herbal extract was added to the nanogels and coated on cotton fabric. The morphology and size of the composite nanogels, chemical structure, biological, and antibacterial properties were evaluated. According to DLS results, TGK2:1 (ratio of TG to keratin = 2:1) had the minimum size (80 nm) and PDI (0.1), and therefore, this sample was chosen as the optimum one. FESEM and TEM images showed the semi-spherical shape of the produced nanogels. FTIR spectra revealed the possible hydrogen bonding between the components, and the formation of disulfide bonds after the addition of hydrogen peroxide was confirmed by XPS. After loading cinnamon into the nanogels, an increase in size was observed from 80 nm for free-nanogel to 85 and 105 nm for 5 and 10% extract-loaded nanogels, respectively. Besides, more cinnamon was released from the treated fabrics by increasing time and cinnamon concentration. The antibacterial test exhibited good antibacterial properties against both Gram-positive and Gram-negative bacteria. Finally, MTT assay approved the biocompatibility of the produced nanogels for potential use in medical textiles.
The Snow-Friction of Freestyle Skis and Snowboards Predicted From Snow Physical Quantities
Authors: Wolfsperger Fabian , Meyer Frédéric , Gilgien Matthias
Published: September 2021

Previous research has shown that friction between ski and snow can vary substantially due to changes in snow conditions. The variation of friction affects the speed a freestyle skier or snowboarder (athlete) reaches during the in-run of a jump. Athletes risk severe injuries if their take-off speed is not within the right margin to land in the “sweet spot” zone. To reduce the risk of injury, snow park designers and competition managers need to calculate the speed athletes reach during the in-run. However, despite multiple attempts over the last decades, to date no model can predict ski-snow friction from snow physical quantities. Hence, simulations of in-run speeds suffer from insufficient validity. For the first time, this work combines kinematic athlete data and comprehensive snow surface measurements to infer the coefficient of friction of freestyle skis and snowboards across a wide range of snow conditions. Athletes’ point mass kinematics were recorded at more than 200 straight gliding runs with differential global navigation satellite systems. The subjects’ air drag and lift were deployed from wind tunnel measurements. Along with the kinematic data and data from wind measurements, a mechanical model of the athlete was established to solve the equation of motion for the coefficient of friction between ski/snowboard and snow. The friction coefficients for ski (snowboard) ranged from 0.023 ± 0.006 (0.026 ± 0.008) to 0.139 ± 0.018 (0.143 ± 0.017) and could be explained well (Radj2= 0.77) from the measured snow parameters using a multivariate statistical model. Our results provide a new quantitative tool for practitioners to predict the friction of skis and snowboard on snow of various conditions, which aims to increase athletes’ safety in slopestyle and big air.
Initial Blood pH, Lactate and Base Deficit Add No Value to Peri-Arrest Factors in Prognostication of Neurological Outcome After Out-of-Hospital Cardiac Arrest
Authors: Mueller Matthias , Grafeneder Juergen , Schoergenhofer Christian , Schwameis Michael , Schriefl Christoph , Poppe Michael , Clodi Christian , Koch Moritz , Sterz Fritz , Holzer Michael , Ettl Florian
Published: September 2021

Background: In cardiac arrest survivors, metabolic parameters [pH value, lactate concentration, and base deficit (BD)] are routinely added to peri-arrest factors (including age, sex, bystander cardiopulmonary resuscitation, shockable first rhythm, resuscitation duration, adrenaline dose) to enhance early outcome prediction. However, the additional value of this strategy remains unclear.

Methods: We used our resuscitation database to screen all patients ≥18 years who had suffered in- or out-of-hospital cardiac arrest (IHCA, OHCA) between January 1st, 2005 and May 1st, 2019. Patients with incomplete data, without return of spontaneous circulation or treatment with sodium bicarbonate were excluded. To analyse the added value of metabolic parameters to prognosticate neurological function, we built three models using logistic regression. These models included: (1) Peri-arrest factors only, (2) peri-arrest factors plus metabolic parameters and (3) metabolic parameters only. Receiver operating characteristics curves regarding 30-day good neurological function (Cerebral Performance Category 1-2) were analysed.

Results: A total of 2,317 patients (OHCA: n = 1842) were included. In patients with OHCA, model 1 and 2 had comparable predictive value. Model 3 was inferior compared to model 1. In IHCA patients, model 2 performed best, whereas both metabolic (model 3) and peri-arrest factors (model 1) demonstrated similar power. PH, lactate and BD had interchangeable areas under the curve in both IHCA and OHCA.

Conclusion: Although metabolic parameters may play a role in IHCA, no additional value in the prediction of good neurological outcome could be found in patients with OHCA. This highlights the importance of accurate anamnesis especially in patients with OHCA.
Widefield Swept-Source Optical Coherence Tomography Angiography Assessment of Choroidal Changes in Vogt-Koyanagi-Harada Disease
Authors: Qian Yujing , Yang Jingyuan , Liang Anyi , Zhao Chan , Gao Fei , Zhang Meifen
Published: September 2021

Purpose: To investigate choroidal changes in patients with Vogt-Koyanagi-Harada disease (VKH) using widefield swept-source optical coherence tomography angiography (SS-OCTA).

Methods: In this cross-sectional study, 133 eyes of 69 patients with VKH (52 eyes of 28 active VKH patients and 81 eyes of 41 inactive VKH patients) and 104 eyes of 52 age and sex matched healthy volunteers were imaged using a widefield SS-OCTA instrument. On 12 mm × 12 mm OCTA scans, mean choroidal thickness (MCT), choroidal vascularity index (CVI), choriocapillaris (CC) flow area, and mean retinal thickness (MRT) were separately calculated in the fovea (diameter of 1 mm) and in concentric rings with different radii (1–3, 3–6, 6–9, and 9–12 mm).

Results: Eyes with active VKH showed significant increases in MCT, CVI, and MRT, and decreased CC flow area in all central and peripheral regions (0–1, 1–3, 3–6, 6–9, and 9–12 mm) than in the healthy eyes (p ≤ 0.01) and inactive VKH eyes (p < 0.05). Inactive VKH eyes only showed marked decrease in CC flow area in all regions compared with controls (p < 0.05). Flow voids were observed in 51 of 52 (98.1%) active VKH eyes and 50 of 81 (61.7%) inactive VKH eyes on 12 mm × 12 mm OCTA. The MCT of all regions was significantly correlated with age, disease duration, and disease activity, whereas CVI was associated with age and disease activity. The CC flow void was related to visual acuity in all regions (p < 0.05).

Conclusion: Widefield SS-OCTA enables a more comprehensive evaluation of chorioretinal changes in patients with VKH disease. Structural and vascular abnormalities are observed in both the central and peripheral choroid and are closely correlated with disease activity.
A Taxon-Wise Insight Into Rock Weathering and Nitrogen Fixation Functional Profiles of Proglacial Systems
Authors: Varliero Gilda , Anesio Alexandre M. , Barker Gary L. A.
Published: September 2021

The Arctic environment is particularly affected by global warming, and a clear trend of the ice retreat is observed worldwide. In proglacial systems, the newly exposed terrain represents different environmental and nutrient conditions compared to later soil stages. Therefore, proglacial systems show several environmental gradients along the soil succession where microorganisms are active protagonists of the soil and carbon pool formation through nitrogen fixation and rock weathering. We studied the microbial succession of three Arctic proglacial systems located in Svalbard (Midtre Lovénbreen), Sweden (Storglaciären), and Greenland (foreland close to Kangerlussuaq). We analyzed 65 whole shotgun metagenomic soil samples for a total of more than 400 Gb of sequencing data. Microbial succession showed common trends typical of proglacial systems with increasing diversity observed along the forefield chronosequence. Microbial trends were explained by the distance from the ice edge in the Midtre Lovénbreen and Storglaciären forefields and by total nitrogen (TN) and total organic carbon (TOC) in the Greenland proglacial system. Furthermore, we focused specifically on genes associated with nitrogen fixation and biotic rock weathering processes, such as nitrogenase genes, obcA genes, and genes involved in cyanide and siderophore synthesis and transport. Whereas we confirmed the presence of these genes in known nitrogen-fixing and/or rock weathering organisms (e.g., Nostoc, Burkholderia), in this study, we also detected organisms that, even if often found in soil and proglacial systems, have never been related to nitrogen-fixing or rock weathering processes before (e.g., Fimbriiglobus, Streptomyces). The different genera showed different gene trends within and among the studied systems, indicating a community constituted by a plurality of organisms involved in nitrogen fixation and biotic rock weathering, and where the latter were driven by different organisms at different soil succession stages.
Kinetic Characterization and Inhibitor Screening of Pyruvate Kinase I From Babesia microti
Authors: An Xiaomeng , Yu Long , Wang Sen , Ao Yangsiqi , Zhan Xueyan , Liu Qin , Zhao Yangnan , Li Muxiao , Shu Xiang , Li Fangjie , He Lan , Zhao Junlong
Published: September 2021

The apicomplexan Babesia microti is a main pathogenic parasite causing human babesiosis, which is one of the most widely distributed tick-borne diseases in humans. Pyruvate kinase (PYK) plays a central metabolic regulatory role in most living organisms and catalyzes the essentially irreversible step in glycolysis that converts phosphoenolpyruvate (PEP) to pyruvate. Hence, PYK is recognized as an attractive therapeutic target in cancer and human pathogens such as apicomplexans. In this study, we cloned, expressed, and purified B. microti PYK I (BmPYKI). Western blotting illustrated that anti-rBmPYKI antibody could specifically recognize the native BmPYKI protein in the lysate of B. microti with a 54-kDa band, which is consistent with the predicted size. In addition, the enzymatic activity of the purified recombinant PYKI (rPYKI) was tested under a range of pH values. The results showed that the maximum catalytic activity could be achieved at pH 7.0. The saturation curves for substrates demonstrated that the Km value for PEP was 0.655 ± 0.117 mM and that for ADP was 0.388 ± 0.087 mM. We further investigated the effect of 13 compounds on rBmPYKI. Kinetic analysis indicated that six inhibitors (tannic acid, shikonin, apigenin, PKM2 inhibitor, rosiglitazone, and pioglitazone) could significantly inhibit the catalytic activity of PYKI, among which tannic acid is the most efficient inhibitor with an IC50 value 0.49 μM. Besides, four inhibitors (tannic acid, apigenin, shikonin, and PKM2 inhibitor) could significantly decrease the growth of in vitro-cultured B. microti with IC50 values of 0.77, 2.10, 1.73, and 1.15 μM. Overall, the present study provides a theoretical basis for the design and development of new anti-Babesia drugs.
Untargeted Metabolomics Investigation on Selenite Reduction to Elemental Selenium by Bacillus mycoides SeITE01
Authors: Baggio Greta , Groves Ryan A. , Chignola Roberto , Piacenza Elena , Presentato Alessandro , Lewis Ian A. , Lampis Silvia , Vallini Giovanni , Turner Raymond J.
Published: September 2021

Bacillus mycoides SeITE01 is an environmental isolate that transforms the oxyanion selenite (SeO32−) into the less bioavailable elemental selenium (Se0) forming biogenic selenium nanoparticles (Bio-SeNPs). In the present study, the reduction of sodium selenite (Na2SeO3) by SeITE01 strain and the effect of SeO32− exposure on the bacterial cells was examined through untargeted metabolomics. A time-course approach was used to monitor both cell pellet and cell free spent medium (referred as intracellular and extracellular, respectively) metabolites in SeITE01 cells treated or not with SeO32−. The results show substantial biochemical changes in SeITE01 cells when exposed to SeO32−. The initial uptake of SeO32− by SeITE01 cells (3h after inoculation) shows both an increase in intracellular levels of 4-hydroxybenzoate and indole-3-acetic acid, and an extracellular accumulation of guanosine, which are metabolites involved in general stress response adapting strategies. Proactive and defensive mechanisms against SeO32− are observed between the end of lag (12h) and beginning of exponential (18h) phases. Glutathione and N-acetyl-L-cysteine are thiol compounds that would be mainly involved in Painter-type reaction for the reduction and detoxification of SeO32− to Se0. In these growth stages, thiol metabolites perform a dual role, both acting against the toxic and harmful presence of the oxyanion and as substrate or reducing sources to scavenge ROS production. Moreover, detection of the amino acids L-threonine and ornithine suggests changes in membrane lipids. Starting from stationary phase (24 and 48h), metabolites related to the formation and release of SeNPs in the extracellular environment begin to be observed. 5-hydroxyindole acetate, D-[+]-glucosamine, 4-methyl-2-oxo pentanoic acid, and ethanolamine phosphate may represent signaling strategies following SeNPs release from the cytoplasmic compartment, with consequent damage to SeITE01 cell membranes. This is also accompanied by intracellular accumulation of trans-4-hydroxyproline and L-proline, which likely represent osmoprotectant activity. The identification of these metabolites suggests the activation of signaling strategies that would protect the bacterial cells from SeO32− toxicity while it is converting into SeNPs.
The Response of Critical Microbial Taxa to Litter Micro-Nutrients and Macro-Chemistry Determined the Agricultural Soil Priming Intensity After Afforestation
Authors: Yang Hongling , Li Yulin , Wang Shaokun , Zhan Jin , Ning Zhiying , Han Dan
Published: September 2021

Afforestation with trees and shrubs around cropland can effectively decrease soil degradation and avoid sand storms, but subsequent modification of litter quality accelerates the degradation of native organic matter via the soil priming effect (PE). Although carbon accumulation in agricultural soils after afforestation was widely studied, little is known about the extent to which soil organic carbon (SOC) mineralization is induced by complex residue input in agro-forest-grass composite ecosystems. Here, we mixed corn field soil and litter of afforestation tree and shrub species together in a micro-environment to quantify the effects of litter-mixture input on farmland soil priming associated with afforestation. Additionally, we studied the responses of bacterial and fungal species to litter chemistry, with the aim to identify the litter and microbial driver of soil priming. The results showed that soil priming was accelerated by different litter addition which varied from 24 to 74% of SOC mineralization, suggesting that priming intensity was relatively flexible and highly affected by litter quality. We also find that the macro-chemistry (including litter carbon, nitrogen, lignin, and cellulose) directly affects priming intensity, while micro-chemistry (including litter soluble sugar, water-soluble phenol, methanol-soluble phenol, and condensed tannin) indirectly influences priming via alteration to dominant bacterial taxa. The stepwise regression analysis suggested that litter nitrogen and cellulose were the critical litter drivers to soil priming (r2 = 0.279), and the combination of bacterial phylum Proteobacteria, Firmicutes, Bacteroidetes, Acidobacteria, and fungal taxa Eurotiomycetes was a great model to explain the priming intensity (r2 = 0.407).
Recent Insights Into the Molecular Mechanism of Toll-Like Receptor Response to Dengue Virus Infection
Authors: Kayesh Mohammad Enamul Hoque , Kohara Michinori , Tsukiyama-Kohara Kyoko
Published: September 2021

Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease caused by dengue virus (DENV). Recently, DENV has been affecting humans within an expanding geographic range due to the warming of the earth. Innate immune responses play a significant role in antiviral defense, and Toll-like receptors (TLRs) are key regulators of innate immunity. Therefore, a detailed understanding of TLR and DENV interactions is important for devising therapeutic and preventive strategies. Several studies have indicated the ability of DENV to modulate the TLR signaling pathway and host immune response. Vaccination is considered one of the most successful medical interventions for preventing viral infections. However, only a partially protective dengue vaccine, the first licensed dengue vaccine CYD-TDV, is available in some dengue-endemic countries to protect against DENV infection. Therefore, the development of a fully protective, durable, and safe DENV vaccine is a priority for global health. Here, we demonstrate the progress made in our understanding of the host response to DENV infection, with a particular focus on TLR response and how DENV avoids the response toward establishing infection. We also discuss dengue vaccine candidates in late-stage development and the issues that must be overcome to enable their success.
Role of BET Proteins in Inflammation and CNS Diseases
Authors: Liu Lei , Yang Changjun , Candelario-Jalil Eduardo
Published: September 2021

Bromodomain and extra-terminal domain (BET) proteins consist of four mammalian members (BRD2, BRD3, BRD4, and BRDT), which play a pivotal role in the transcriptional regulation of the inflammatory response. Dysregulated inflammation is a key pathological process in various CNS disorders through multiple mechanisms, including NF-κB and Nrf2 pathways, two well-known master regulators of inflammation. A better mechanistic understanding of the BET proteins’ role in regulating the inflammatory process is of great significance since it could reveal novel therapeutic targets to reduce neuroinflammation associated with many CNS diseases. In this minireview, we first outline the structural features of BET proteins and summarize genetic and pharmacological approaches for BET inhibition, including novel strategies using proteolysis-targeting chimeras (PROTACs). We emphasize in vitro and in vivo evidence of the interplay between BET proteins and NF-κB and Nrf2 signaling pathways. Finally, we summarize recent studies showing that BET proteins are essential regulators of inflammation and neuropathology in various CNS diseases.
Atypical Posterior Reversible Encephalopathy Syndrome in a Postpartum Woman With Moyamoya Disease: A Case Report and Literature Review
Authors: Zou Ning , Guo Guixiang , Wan Fangchao , Li Xin
Published: September 2021

Background: Moyamoya disease is a rare cerebrovascular occlusive disease, which is characterized by stenosis and gradual occlusion of the internal carotid arteries, causing the progression of characteristic collateral vessels. To date, most studies investigating moyamoya disease have focused on medical implications, and the potential implications for neurocognitive and/or neuropsychiatric functioning were inconclusive.

Case Presentation: we present a case of a 26-year-old Chinese postpartum woman who presented to the emergency department with a 19-h history of cognitive decline, vomiting, and convulsions. Blood pressure, heart rate, and respiration rate were 200/120 mmHg, 115 beats/minute, and 30 breaths/minute, respectively, on arrival. The Glasgow Coma Scale, modified RANKIN scale (mRS), and National Institute of Health stroke scale (NIHSS) scores were 3, 5, and 18, respectively. Moyamoya disease was diagnosed using cerebral angiography and digital subtraction angiography. The cognitive functions of orientation, use of language, ability to calculate, and memory significantly improved after 11 days of treatment (Glasgow Coma Scale: 15; mRS: 0; NIHSS: 0).

Conclusions:This patient was diagnosed with reversible posterior leukoencephalopathy syndrome related to moyamoya disease. This case highlights that atypical posterior reversible encephalopathy syndrome can occur in patients with moyamoya disease, and should be considered for the differential diagnosis of cerebral infarcts and hemorrhage in a postpartum female.