bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive and Developmental Toxicity Assessment of Human Umbilical Cord Mesenchymal Stem Cells in Rats
Authors: Li Xiaobo , Huang Qijing , Zhang Xiangxiang , Xie Changfeng , Liu Muyun , Yuan Yueming , Feng Jianjia , Xing Haoyu , Ru Li , Yuan Zheng , Xu Zhiyong , Yang YaoXiang , Long Yan , Xing Chengfeng , Song Jianping , Hu Xiang , Xu Qin
Published: May 2022

Objective: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have shown very attractive potential in clinical applications for the treatment of various diseases. However, the data about the reproductive and developmental toxicity of hUC-MSCs remains insufficient. Thus, we assessed the potential effects of intravenous injection of hUC-MSCs on reproduction and development in Sprague-Dawley rats.

Methods: In the fertility and early embryonic development study, hUC-MSCs were administered at dose levels of 0, 6.0 × 106, 8.5 × 106, and 1.2 × 107/kg to male and female rats during the pre-mating, mating and gestation period. In the embryo-fetal development study, the pregnant female rats received 0, 6.0 × 106, 1.2 × 107, and 2.4 × 107/kg of hUC-MSCs from gestation days (GD) 6–15. Assessments made included mortality, clinical observations, body weight, food consumption, fertility parameters of male and female, litter, and fetus parameters, etc.

Results: No hUC-MSCs-related toxicity was observed on the fertility of male and female rats, and no teratogenic effect on fetuses. hUC-MSCs at 1.2 × 107/kg caused a mildly decrease in body weight gain of male rats, transient listlessness, tachypnea, and hematuria symptoms in pregnant female rats. Death was observed in part of the pregnant females at a dose of 2.4 × 107/kg, which could be due to pulmonary embolism.

Conclusion: Based on the results of the studies, the no-observed-adverse-effect levels (NOAELs) are 8.5 × 106/kg for fertility and early embryonic development, 1.2 × 107/kg for maternal toxicity and 2.4 × 107/kg for embryo-fetal development in rats intravenous injected with hUC-MSCs, which are equivalent to 8.5-fold, 12-fold, and 24-fold respectively of its clinical dosage in humans. These findings may provide a rational basis for human health risk assessment of hUC-MSCs.
Dynamic Changes in the Aorta During the Cardiac Cycle Analyzed by ECG-Gated Computed Tomography
Authors: Zhu Wenying , Wang Yingliang , Chen Yang , Liu Jiacheng , Zhou Chen , Shi Qin , Huang Songjiang , Yang Chongtu , Li Tongqiang , Xiong Bin
Published: May 2022

Background

To characterize the difference in aortic dimensions during the cardiac cycle with electrocardiogram (ECG)-gated computed tomography angiography (CTA) and to determine whether other parameters in comparison to diameter could potentially provide a more accurate size reference for stent selection at the aortic arch and the proximal thoracic descending aorta.

Methods

The CTA imaging of 90 patients during the cardiac cycle was reviewed. Three anatomic locations were selected for analysis (level A: 1 cm proximal to the innominate artery; level B: 1 cm distal to the left common carotid artery; and level C: 1 cm distal to the left subclavian artery). We measured the maximum diameter, the minimum diameter, the lumen area, the lumen perimeter, and the diameter derived from the lumen area, and the changes of each parameter at each level during the cardiac cycle were compared.

Results

The mean age was 60.9 ± 12.4 years (range, 16–78 years). There was a significant difference in the aortic dimensions during the cardiac cycle (p < 0.001). The diameter derived from the lumen area at all three levels was changed least over time when compared to the area, perimeter, and the maximum aortic diameter (all p < 0.01).

Conclusion

The aortic dimensional differences during the cardiac cycle are significant. The aortic diameter derived from the lumen area over other parameters may provide a better evaluation for selecting the size of the stent at the aortic arch and the proximal thoracic descending aorta. A prospective study comparing these different measurement parameters regarding the outcomes is still needed to evaluate the clinical implications.
Benefits of a Supervised Ambulatory Outpatient Program in a Cardiovascular Rehabilitation Unit Prior to a Heart Transplant: A Case Study
Authors: Poty Antoine , Krim Florent , Lopes Philippe , Garaud Yves , Leprêtre Pierre-Marie
Published: May 2022

Preoperative peak oxygen uptake (V.O2peak) and ventilatory efficiency (V.E/V.CO2slope) are related to the vital prognosis after cardiac transplantation (HTx). The objective of our study was to evaluate the effects of exercise-based cardiac rehabilitation (ECR) program on the preoperative exercise capacity of a HTx candidate. A male patient, aged 50–55 years, with chronic heart failure was placed on the HTx list and performed 12 weeks of intensive ECR (5 sessions-a-week). Our results showed that the cardiac index continuously increased between the onset and the end of ECR (1.40 vs. 2.53 L.min–1.m2). The first 20 sessions of ECR induced a V.O2peak increase (15.0 vs. 19.3 ml.min–1.kg–1, corresponding to 42.0 and 53.0% of its maximal predicted values, respectively). The peak V.O2 plateaued between the 20th and the 40th ECR session (19.3 vs. 19.4 ml.min–1.kg–1) then progressively increased until the 60th ECR session to reach 25.7 ml.min–1.kg–1, i.e., 71.0% of the maximal predicted values. The slope of V.E/V.CO2 showed a biphasic response during the ECR program, with an increase between the onset and the 20th ECR session (58.02 vs. 70.48) and a decrease between the 20th and the 40th ECR session (70.48 vs. 40.94) to reach its minimal value at the 60th ECR session (31.97). After the first 40 sessions of the ECR program, the Seattle Heart Failure Model score predicted median survival time was estimated at 7.2 years. In conclusion, the improvement in exercise capacity and cardiorespiratory function following the ECR helped delay the heart transplant surgery in our patient awaiting heart transplantation.
Is the Risk of Diabetes Lower in Patients With Atrial Fibrillation Treated With Direct Oral Anticoagulant Compared to Warfarin?
Authors: Liu Xuyang , Feng Shenghui , Chen Zhuohui , Zhou Yue , Yin Kang , Xue Zhengbiao , Zhu Wengen
Published: May 2022

Background

The use of anticoagulants is an established strategy to prevent stroke, embolism, and cardiovascular mortality in patients with atrial fibrillation (AF), but its role in the prevention of incident diabetes is unclear. We aimed to investigate this question by using participant data from cohort studies.

Methods

We conducted a meta-analysis of participants to investigate the impact of direct oral anticoagulants (DOACs) on the risk of new-onset diabetes in AF patients. The collection of related data was performed in the PubMed and EMBASE databases until December 2021, including studies associated with evaluating the correlation between DOACs and incident diabetes. The hazard ratios (HRs) and 95% confidence intervals (CIs) were adjusted by the random-effects model with an inverse variance method.

Results

Two cohort studies with a total of 24,434 patients were included in this study (warfarin: n = 6,906; DOACs: n = 17,528). Compared with warfarin, the use of DOACs could reduce the incident diabetic risk in AF patients (HR = 0.75, 95%CI: 0.68–0.82). Investigations about the effects of three major classes of DOACs showed that the individual use of dabigatran (HR = 0.76, 95%CI: 0.64–0.90), rivaroxaban (HR = 0.74, 95%CI: 0.64–0.87), apixaban (HR = 0.74, 95%CI: 0.60–0.92) and the combined use of rivaroxaban and apixaban (HR = 0.74, 95%CI: 0.66–0.84) could reduce the risk of new-onset diabetes compared with warfarin. This risk reduction effect could be observed in both male and female groups (HR = 0.73, 95%CI: 0.64–0.84, P < 0.00001; HR = 0.82, 95%CI: 0.82–0.99, P = 0.04).

Conclusions

Treatment with DOACs compared with warfarin reduced the risk of new-onset diabetes in both male and female patients with AF.
Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation
Authors: Lazzerini Pietro Enea , Accioli Riccardo , Acampa Maurizio , Zhang Wen-Hui , Verrengia Decoroso , Cartocci Alessandra , Bacarelli Maria Romana , Xin Xiaofeng , Salvini Viola , Chen Ke-Su , Salvadori Fabio , D’errico Antonio , Bisogno Stefania , Cevenini Gabriele , Marzotti Tommaso , Capecchi Matteo , Laghi-Pasini Franco , Chen Long , Capecchi Pier Leopoldo , Boutjdir Mohamed
Published: May 2022

Background

Heart rate-corrected QT interval (QTc) prolongation is prevalent in patients with severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. Recent evidence suggests that the exaggerated host immune-inflammatory response characterizing the disease, specifically interleukin-6 (IL-6) increase, may have an important role, possibly via direct effects on cardiac electrophysiology. The aim of this study was to dissect the short-term discrete impact of IL-6 elevation on QTc in patients with severe COVID-19 infection and explore the underlying mechanisms.

Methods

We investigated the following mechanisms: (1) the QTc duration in patients with COVID-19 during the active phase and recovery, and its association with C-reactive protein (CRP) and IL-6 levels; (2) the acute impact of IL-6 administration on QTc in an in vivo guinea pig model; and (3) the electrophysiological effects of IL-6 on ventricular myocytes in vitro.

Results

In patients with active severe COVID-19 and elevated IL-6 levels, regardless of acute myocardial injury/strain and concomitant QT-prolonging risk factors, QTc was significantly prolonged and rapidly normalized in correlation with IL-6 decrease. The direct administration of IL-6 in an in vivo guinea pig model acutely prolongs QTc duration. Moreover, ventricular myocytes incubated in vitro with IL-6 show evident prolongation in the action potential, along with significant inhibition in the rapid delayed rectifier potassium current (IKr).

Conclusion

For the first time, we demonstrated that in severe COVID-19, systemic inflammatory activation can per se promote QTc prolongation via IL-6 elevation, leading to ventricular electric remodeling. Despite being transitory, such modifications may significantly contribute to arrhythmic events and associated poor outcomes in COVID-19. These findings provide a further rationale for current anti-inflammatory treatments for COVID-19, including IL-6-targeted therapies.
RETRACTED: Postoperative Pulmonary Complications in Patients With Transcatheter Tricuspid Valve Implantation—Implications for Physiotherapists
Authors: Yu Peng-Ming , Wang Yu-Qiang , Luo Ze-Ruxing , Tsang Raymond C. C. , Tronstad Oystein , Shi Jun , Guo Ying-Qiang , Jones Alice Y. M.
Published: May 2022

Objectives

To investigate the incidence of postoperative pulmonary complications (PPCs) and short-term recovery after transcatheter tricuspid valve implantation (TTVI).

Methods

A total of 17 patients diagnosed with severe tricuspid regurgitation who received a LuX-valve TTVI were included in this study. Spirometry lung function, maximal inspiratory pressure (MIP), and 6-min walk test distance (6MWD) were recorded. Prior to surgery, patients were stratified into high or low pulmonary risk groups based on published predefined criteria. A physiotherapist provided all patients with education on thoracic expansion exercises, effective cough and an inspiratory muscle training protocol at 50% of MIP for 3 days preoperatively. All patients received standard post-operative physiotherapy intervention including positioning, thoracic expansion exercises, secretion removal techniques and mobilization. Patients were assessed for PPCs as defined by the Melbourne-Group Score-version 2. Clinical characteristics and hospital stay, cost, functional capacity, and Kansas City Cardiomyopathy Questionnaire (KCCQ) heart failure score were recorded at admission, 1-week, and 30-days post-op.

Results

The mean (SD) age of the 17 patients was 68.4 (8.0) years and 15 (88%) were female. Pre-surgical assessment identified 8 patients (47%) at high risk of PPCs. A total of 9 patients (53%) developed PPCs between the 1st and 3rd day post-surgery, and 7 of these 9 patients were amongst the 8 predicted as “high risk” prior to surgery. One patient died before the 30 day follow up. Pre-operative pulmonary risk assessment score, diabetes mellitus, a low baseline MIP and 6MWD were associated with a high incidence of PPCs. Compared to those without PPCs, patients with PPCs had longer ICU and hospital stay, and higher hospitalization cost. At 30 days post-surgery, patients without PPCs maintained higher MIP and 6MWD compared to those with PPCs, but there were no significant between-group differences in other lung function parameters nor KCCQ.

Conclusion

This is the first study to report the incidence of PPCs post TTVI. Despite a 3-day prehabilitation protocol and standard post-operative physiotherapy, PPCs were common among patients after TTVI and significantly impacted on hospital and short-term recovery and outcomes. In the majority of patients, PPCs could be accurately predicted before surgery. A comprehensive prehabilitation program should be considered for patients prior to TTVI.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [ChiCTR2000039671].
Curcumin Improves Cardiopulmonary Resuscitation Outcomes by Modulating Mitochondrial Metabolism and Apoptosis in a Rat Model of Cardiac Arrest
Authors: Zhang Jie , Liu Siqi , Jiang Longyuan , Hou Jingying , Yang Zhengfei
Published: May 2022

Background

Curcumin, a diarylheptanoid chemical compound extracted from curcuma longa, exerts a variety of biological and pharmacological effects in numerous pathological conditions, including ischemia/reperfusion (I/R) injury. In this study, we investigated its role in post-resuscitation myocardial dysfunction in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) by targeting on mitochondrial metabolism and apoptosis.

Methods

Animals were randomized into three groups: sham, control and curcumin, with fifteen rats in each group. Ventricular fibrillation (VF) was induced in the rats of the control and curcumin groups. The rats in the two groups were untreated for 8 min, followed by CPR for 8 min. Placebo (saline) or curcumin was administered by intraperitoneal injection, respectively, 5 min after successful resuscitation. Myocardial function was measured at baseline and post-resuscitation for 6 h consecutively. Ten rats in each group were closely observed for an additional 66 h to analyze the survival status, and the remaining five were sacrificed for the measurement of mitochondrial parameters and cell apoptosis.

Results

Compared with the control group, myocardial function was significantly enhanced in the curcumin group, contributing to a better survival status. Curcumin treatment mitigated the depletion of superoxide dismutase (SOD) and the production of malondialdehyde (MDA). The structural damage of mitochondria was also alleviated, with improved conditions of mPTP and ΔΨm. Curcumin boosted the production of ATP and attenuated myocardial apoptosis. Cytochrome C, caspase-3 and its cleavage were suppressed by curcumin. Proteins closely related to the functional performance of mitochondria, including uncoupling protein 2 (UCP2) and uncoupling protein 3 (UCP3) were downregulated, while mitochondrial transcription factor A (mtTFA) was upregulated.

Conclusion

Curcumin improves the outcomes of CPR via alleviating myocardial dysfunction induced by I/R injury. It exhibits anti-oxidation properties. Moreover, it is capable of ameliorating mitochondrial structure and energy metabolism, as well as inhibiting the mitochondrial apoptosis pathway. UCP2, UCP3, and mtTFA might also be involved in curcumin mediated protective effects on mitochondria.
Tongan Volcanic Eruption Intensifies Tropical Cyclone Cody (2022)
Authors: Liu Haiyang , Tang Xiaodong
Published: May 2022

The aerosol−cloud impacts of the Tongan volcanic eruptions on the nearby tropical cyclone (TC) Cody on January 14∼15, 2022 are investigated by the MODIS satellite and ERA5 reanalysis data. Both the precipitation and intensity of Cody were obviously enhanced after the main blast of the Tongan volcanic eruption on January 15, although the sea surface temperature and vertical wind shear of the environmental wind did not change much according to ERA5 data. The vision that a large amount of volcanic aerosol flowed from the Tongan eruption into the inflow of Cody was captured by the MODIS observations on January 15. The cloud top temperature dropped, and the cloud particle effective radius decreased in Cody from then on, which indicated the occurrence of deep convection. The analyzed results of ERA5 show that convection was strengthened in the periphery of Cody at the beginning of the volcanic eruption at 03:00 UTC on January 15 and later in Cody’s inner core after the main blast at 06:00 UTC on January 15. This could be because of the microphysical process of aerosol−cloud interactions, which inhibited stratiform precipitation, increased vertical velocity and enhanced convective precipitation further. Since the deep convection in the inner core was conducive to the development of Cody, both the total precipitation and intensity of Cody increased after the main blast of the volcanic eruption. The result also suggests that major volcanic eruptions could increase the convective intensity and induce heavy precipitation in a nearby organized convective system (e.g., TC or mesoscale convective systems).
Social Network Analysis of EduTubers
Authors: Pasquel-López Cynthia , Rodríguez-Aceves Lucía , Valerio-Ureña Gabriel
Published: May 2022

The popularity of educational videos has increased in recent years. In 2018, YouTube announced a $20 million investment to support educational video creators and organized the YouTube EduCon event to bring them together and form a community. The COVID-19 pandemic pushed educational institutions to use resources contained in public repositories, such as YouTube. The objective of this research study was to explore the dynamics of EduTubers to understand the motivations for their interactions. We used social network analysis (SNA) with YouTube data to analyze the dynamics of EduTubers’ recommendation networks. Meaningful insights reveal a relationship between the level of digital engagement and the level of out-degree. Additionally, we confirm that educhannel homophily has a positive effect on the level of reciprocity. The main contribution lies in the use of theoretical concepts (reciprocity and homophily), focusing on the intrinsic motivations of EduTubers to recommend other channels. The practical implications of the results suggest that educhannels that initiate and grow digital engagement are more likely to participate in a recommendation network.
Investigating the Maritime Freight-Induced EKC Hypothesis: The Case of Scandinavian Countries
Authors: YAZICI Sabire
Published: May 2022

Many countries are concerned about environmental dirtiness problems due to CO2 emissions, and they try to fix this issue by developing several policies. The major goal of this study is to reveal the coefficient of influence factors on carbon emissions by considering different time periods within the framework of implementation of policies. In this context, this study explores the relationship between economic growth, energy consumption, and CO2 emissions within the frame of the environmental Kuznets curve hypothesis. However, this article considers the linkage between the logistics sector and CO2 emissions in terms of the environmental Kuznets curve hypothesis for Denmark, Sweden, Norway, and Finland from 1960 to 2015, which replaced the sea transportation as independent aside from (economic growth) gross domestic product and energy consumption. The Fourier Shin co-integration test, fully modified least square, dynamic least square, canonical co-integrating regression, and autoregressive distributed lag bound test models are performed from 1960 to 2015 (as two separate periods) as annual data in order to reveal the long-run relationship between variables within the scope of the environmental Kuznets curve hypothesis for Scandinavian countries including Denmark, Sweden, Norway, and Finland. According to results of the autoregressive distributed lag bound test, if maritime freight increases by 1%, CO2 emissions increases by 0.2723%. A 1% increase in energy consumption increases CO2 emissions by 0.3356%. The short-term autoregressive distributed lag bound test findings ascertain that the major factors of CO2 emissions in the short-term are changed in maritime freight, energy consumption, and gross domestic product at a 1% significance level for Denmark. Due to the explosive growth of the transportation sector, coupled with a significant rise in greenhouse gas emissions from this sector, preventive policies should be followed. In order to avoid pollution from transportation, it is essential to find out its necessary drivers. In addition, policymakers should kick-start applications of new technology in transportation to reduce pollution by releasing new energy-saving vehicles. In this sense, transportation carbon tax and strengthening incentives for energy conservation should be implemented.
Mitigating Carbon Emissions in China: The Role of Clean Energy, Technological Innovation, and Political-Institutional Quality
Authors: Azam Anam , Rafiq Muhammad , Shafique Muhammad , Yuan Jiahai
Published: May 2022

The global warming phenomena arise from the subject of climate change, which draws intellectuals’ attention toward replacing polluting energy sources with clean energy sources by continued deployment of innovations. Also, global warming problems put large pressure on governments, individuals, and policymakers. Therefore, for reliable energy supply and economic development, the target of achieving a low-carbon and sustainable environment is needed. In this light, we explore the role of clean energy and technological innovation in carbon emission reduction in China from 1995 to 2018. The key outcomes from the fully modified least-squares and robust least-squares indicate an elasticity of −0.065 and −0.075, respectively, for the nexus of renewable energy and CO2 emissions. Similarly, nuclear energy, technology innovation, and political-institutional quality have a negative influence on CO2 emissions. Furthermore, the granger causality demonstrates feedback between renewable energy and CO2 emissions, as well as between technological innovation and CO2 emissions. To achieve a cleaner environment, the implementation of the existing policy pathways is potentially geared toward applying technological innovations to produce renewable energy at lower costs.
Collapse of Breeding Success in Desert-Dwelling Hornbills Evident Within a Single Decade
Authors: Pattinson Nicholas B. , van de Ven Tanja M. F. N. , Finnie Mike J. , Nupen Lisa J. , McKechnie Andrew E. , Cunningham Susan J.
Published: May 2022

Rapid anthropogenic climate change potentially severely reduces avian breeding success. While the consequences of high temperatures and drought are reasonably well-studied within single breeding seasons, their impacts over decadal time scales are less clear. We assessed the effects of air temperature (Tair) and drought on the breeding output of southern yellow-billed hornbills (Tockus leucomelas; hornbills) in the Kalahari Desert over a decade (2008–2019). We aimed to document trends in breeding performance in an arid-zone bird during a time of rapid global warming and identify potential drivers of variation in breeding performance. The breeding output of our study population collapsed during the monitoring period. Comparing the first three seasons (2008–2011) of monitoring to the last three seasons (2016–2019), the mean percentage of nest boxes that were occupied declined from 52% to 12%, nest success from 58% to 17%, and mean fledglings produced per breeding attempt from 1.1 to 0.4. Breeding output was negatively correlated with increasing days on which Tmax (mean maximum daily Tair) exceeded the threshold Tair at which male hornbills show a 50% likelihood of engaging in heat dissipation behavior [i.e., panting (Tthresh; Tair = 34.5°C)] and the occurrence of drought within the breeding season, as well as later dates for entry into the nest cavity (i.e., nest initiation) and fewer days post-hatch, spent incarcerated in the nest by the female parent. The apparent effects of high Tair were present even in non-drought years; of the 115 breeding attempts that were recorded, all 18 attempts that had ≥ 72% days during the attempt on which Tmax > Tthresh failed (equivalent to Tmax during the attempt ≥ 35.7°C). This suggests that global warming was likely the primary driver of the recent, rapid breeding success collapse. Based on current warming trends, the Tmax threshold of 35.7°C, above which no successful breeding attempts were recorded, will be exceeded during the entire hornbill breeding season by approximately 2027 at our study site. Therefore, our findings support the prediction that climate change may drive rapid declines and cause local extinctions despite the absence of direct lethal effects of extreme heat events.
Infanticide by Adult Females Causes Sexual Conflict in a Female-Dominated Social Mammal
Authors: East Marion L. , Thierer Dagmar , Benhaiem Sarah , Metzger Sonja , Hofer Heribert
Published: May 2022

Infanticide by adult females includes any substantial contribution to the demise of young and inevitably imposes fitness costs on the victim’s genetic fathers, thereby generating sexual conflict with them. Few if any studies have quantified the impact of infanticide by females on male reproductive success, the magnitude of sexual conflict this causes and possible counterstrategies males use against infanticidal females. We examine these topics in spotted hyena (Crocuta crocuta) clans, where females socially dominate breeding males and strong female mate-choice is independent of male social status. We consider two causes of infanticide by females, violent attacks on cubs and fatal maternal neglect. Violent attacks are predicted during periods of social instability at the top of the female linear dominance hierarchy and victims are expected to predominantly have mothers above median rank. Fatal maternal neglect, when starving litters are abandoned, is associated with monopolization of food in clan territories by high-ranking females, and victims are predicted to have mothers below median rank. Female perpetrators of violent attacks are expected to reduce the reproductive success of the fathers of their victims more than perpetrators of fatal maternal neglect. We tested these predictions using 30 + years of data (54 recorded violent attacks, 43 cases of fatal maternal neglect, DNA profiling of 1,671 individuals). Using long-term observations at communal dens we investigated whether males use counterstrategies against infanticide reported in other mammals. Due to female social dominance over breeding males, strong female mate-choice and prolonged offspring dependence on lactation in spotted hyenas, we predicted that these counterstrategies were unlikely to be used by males against females, thus no incidences of them were likely to be observed. Our results revealed that breeding males lost cubs to violent attacks at all stages of their reproductive tenure and to perpetrators with whom they did not sire offspring. Amongst known sources of paternity loss, violent attacks comprised 12.2% and maternal neglect 9.8% of cases. Violent attacks significantly reduced offspring production rates of breeding males, suggesting that infanticide by females generates sexual conflict. As predicted, no evidence of males using counterstrategies against infanticide by females were observed.
Palm Species Traits Determine Soil Nutrient Effects on Seedling Performance
Authors: Collins Colton , Wardle David A. , Andersen Kelly M.
Published: May 2022

Environmental gradients influence plant establishment, survival, and functional traits. Along the Panama Canal Isthmus there is a strong rainfall gradient with an underlying mosaic of soil types ranging in soil nutrient availability. In this region, tree species distribution patterns are correlated with soil phosphorus availability and rainfall patterns, but how understory plant species such as palms relate to these factors is less clear. We hypothesized that due to greater resource use efficiency and optimal biomass allocation, specialist species will have greater seedling performance growing in home soil and sites compared to species not occurring there. To test this hypothesis, we used two specialist species (Chamaedorea tepejilote and Geonoma congesta) and two generalist species (Geonoma cuneata var. cuneata and Chamaedorea pinnatifrons), and for these four species we measured traits on seedlings and assessed their performance in shade house and field transplant experiments using five soils. Soils were sourced from five sites which varied in nutrient availability and rainfall, and were distributed along lowland tropical forests of the Panama Canal Isthmus. In the shadehouse experiment, leaf functional traits were determined by species rather than soil nutrient availability. However, in the shadehouse experiment, seedling biomass allocation, and relative growth rate were determined by interactions between species and soil, with weak support for home-site advantage for one of the species. In the field transplant experiment, seedling survival was strongly related to dry season water availability. However, species tended to have high survival at home sites and other sites with higher dry season rainfall. Together, results from these experiments suggest that understory palm species seedling performance are determined by species-specific responses to the combination of soil nutrient and water availability. This indicates that while soil nutrients influence seedling biomass allocation, dry season water availability determines both specialist and generalist seedling survival and therefore distributions along the soil nutrient and moisture gradient.
Effectiveness of Free Bikes and E-Bikes for Commute Mode Shift: The Case of Google’s Lending Program
Authors: Fitch Dillon T. , Gao Zeyu , Noble Lucy , Mac Terry
Published: May 2022

In 2015, Google began a new transportation demand management program designed to increase bike commuting to their two main corporate campuses in Mountain View and Sunnyvale, CA, United States by lending conventional and electric assisted bikes to employees at no cost to them. Following the lending period, Google incentivized bike purchases, among many other program co-benefits to increase bike commuting. Using a series of bivariate and multivariable analyses, we estimate the program led to average bike commute increases of approximately 1.7–2.3 days per week, roughly a tripling of prior bike commute rates for participating employees. After the program, bike rates of participants diminished slightly, but were still greater than baseline (increase of 1.3–1.9 days per week). Furthermore, nearly all the increases in bicycling are likely attributed to decreases in single occupancy vehicle (SOV) commuting. This study offers a first look at the potential for bike lending as a transportation demand management strategy for large employers in suburban settings which can help other employers design their own programs.
Population Genetics and Phylogeography of Galapagos Fur Seals
Authors: Chaves Jaime A. , Lopes Fernando , Martínez Daniela , Cueva Dario F. , Gavilanes Gabriela I. , Bonatto Sandro L. , de Oliveira Larissa Rosa , Páez-Rosas Diego
Published: May 2022

Pinnipeds found across islands provide an ideal opportunity to examine the evolutionary process of population subdivision affected by several mechanisms. Here, we report the genetic consequences of the geographic distribution of rookeries in Galapagos fur seals (GFS: Arctocephalus galapagoensis) in creating population structure. We show that rookeries across four islands (nine rookeries) are genetically structured into the following major groups: 1) a western cluster of individuals from Fernandina; 2) a central group from north and east Isabela, Santiago, and Pinta; and possibly, 3) a third cluster in the northeast from Pinta. Furthermore, asymmetric levels of gene flow obtained from eight microsatellites found migration from west Isabela to Fernandina islands (number of migrants Nm = 1), with imperceptible Nm in any other direction. Our findings suggest that the marked structuring of populations recovered in GFS is likely related to an interplay between long-term site fidelity and long-distance migration in both male and female individuals, probably influenced by varying degrees of marine productivity.
MCM10 is a Prognostic Biomarker and Correlated With Immune Checkpoints in Ovarian Cancer
Authors: Wu Zhenzhen , Wang Yueyuan , Li Juan , Wang Huiling , Tuo Xunyuan , Zheng Jing
Published: May 2022

Background: Microchromosome maintenance protein 10 (MCM10) is required for DNA replication in all eukaryotes, and it plays a key role in the development of many types of malignancies. However, we currently still do not know the relationship between MCM10 and ovarian cancer (OV) prognosis and immune checkpoints.

Methods: The Gene Expression Profiling Interactive Analysis and Tumor Immunology Estimation Resource (TIMER) databases were used to investigate MCM10 expression in Fan cancer. The Kaplan-Meier Plotter and PrognoScan were used to assess the relationship between MCM10 and OV prognosis. The LinkedOmics database was used to analyze the MCM10 co-expression network and explore GO term annotation and the KEGG pathway. The relationship between MCM10 expression and immune infiltration in OV was investigated using the Tumor Immunology Estimation Resource database. cBioPortal database was used to explore the relationship between MCM10 expression and 25 immune checkpoints. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect MCM10 expression. The prognosis was also analyzed by distinguishing between high and low expression groups based on median expression values.

Results: The results of the three data sets (220,651_s_at, 222,962_s_at and 223,570_at) in KM Plotter all indicated that the overall survivalof the high MCM10 expression group was lower than that of the low expression group OV, and the results of GSE9891 also reached the same conclusion. The expression level of MCM10 was negatively correlated with B cells and CD8+T cells, and positively correlated with CD4+T Cells and Macrophages. GO term annotation and KEGG pathway analysis showed that the co-expressed genes of MCM10 were mainly enriched in cell cycle and DNA replication. The alterations in MCM10 coexisted statistically with the immune checkpoints CTLA4, TNFSF4, TNFSF18, CD80, ICOSLG, LILRB1 and CD200. PCR results displayed that MCM10 was highly expressed in OV tissues, and the increased expression of MCM10 was significantly associated with poor overall survival.

Conclusion: These results demonstrated that high expression of MCM10 was associated with poor prognosis in OV and correlated with immune checkpoints.
Omeprazole Treatment Failure in Gastroesophageal Reflux Disease and Genetic Variation at the CYP2C Locus
Authors: Kee Ping Siu , Maggo Simran D. S. , Kennedy Martin A. , Barclay Murray L. , Miller Allison L. , Lehnert Klaus , Curtis Maurice A. , Faull Richard L. M. , Parker Remai , Chin Paul K. L.
Published: May 2022

Omeprazole is extensively used to manage gastroesophageal reflux disease (GERD). It is primarily metabolized by CYP2C19. The CYP2C19*17 (rs12248560) allele and the recently described CYP2C:TG haplotype (rs11188059 and rs2860840) are associated with increased enzymatic activity, and may reduce omeprazole exposure. This observational study aimed to investigate the association between these genetic variants and omeprazole treatment failure in GERD. We recruited predominantly New Zealand European GERD patients who either did not respond to omeprazole or experienced breakthrough heartburn symptoms despite at least 8 weeks of omeprazole (≥40 mg/day). The GerdQ score was used to gauge symptomatic severity. A total of 55 cases were recruited with a median age (range) of 56 years (19–82) and GerdQ score of 11 (5–17). Of these, 19 (34.5%) were CYP2C19*17 heterozygotes and two (3.6%) were CYP2C19*17 homozygotes. A total of 30 (27.3%) CYP2C:TG haplotypes was identified in our cohort, with seven (12.7%) CYP2C:TG homozygotes, and 16 (29%) CYP2C:TG heterozygotes. No significant differences were observed for overall CYP2C19*17 alleles, CYP2C19*17/*17, overall CYP2C:TG haplotypes, and CYP2C:TG heterozygotes (p > 0.05 for all comparisons). Gastroscopy and 24-h esophageal pH/impedance tests demonstrated objective evidence of GERD in a subgroup of 39 (71%) cases, in which the CYP2C:TG/TG was significantly enriched (p = 0.03) when compared with the haplotype frequencies in a predominantly (91%) New Zealand European reference population, but not the CYP2C19*17/*17 (p > 0.99), when compared with the allele frequencies for the non-Finnish European subset of gnomAD. We conclude that omeprazole treatment failure in GERD is associated with CYP2C:TG/TG, but not CYP2C19*17.
Dietary Supplements and Natural Products: An Update on Their Clinical Effectiveness and Molecular Mechanisms of Action During Accelerated Biological Aging
Authors: Chen Ye , Hamidu Sherif , Yang Xintong , Yan Yiqi , Wang Qilong , Li Lin , Oduro Patrick Kwabena , Li Yuhong
Published: May 2022

Graphical Abstract
Lymph Leakage Promotes Immunosuppression by Enhancing Anti-Inflammatory Macrophage Polarization
Authors: Herrada Andrés A. , Olate-Briones Alexandra , Lazo-Amador Rodrigo , Liu Chaohong , Hernández-Rojas Bairon , Riadi Gonzalo , Escobedo Noelia
Published: May 2022

Lymphatic vasculature is a network of capillaries and vessels capable of draining extracellular fluid back to blood circulation and to facilitate immune cell migration. Although the role of the lymphatic vasculature as coordinator of fluid homeostasis has been extensively studied, the consequences of abnormal lymphatic vasculature function and impaired lymph drainage have been mostly unexplored. Here, by using the Prox1+/– mice with defective lymphatic vasculature and lymphatic leakage, we provide evidence showing that lymph leakage induces an immunosuppressive environment by promoting anti-inflammatory M2 macrophage polarization in different inflammatory conditions. In fact, by using a mouse model of tail lymphedema where lymphatic vessels are thermal ablated leading to lymph accumulation, an increasing number of anti-inflammatory M2 macrophages are found in the lymphedematous tissue. Moreover, RNA-seq analysis from different human tumors shows that reduced lymphatic signature, a hallmark of lymphatic dysfunction, is associated with increased M2 and reduced M1 macrophage signatures, impacting the survival of the patients. In summary, we show that lymphatic vascular leakage promotes an immunosuppressive environment by enhancing anti-inflammatory macrophage differentiation, with relevance in clinical conditions such as inflammatory bowel diseases or cancer.
Case Report: Neuromyelitis Optica Spectrum Disorder With Progressive Elevation of Cerebrospinal Fluid Cell Count and Protein Level Mimicking Infectious Meningomyelitis: A Diagnostic Challenge
Authors: Zhang Yin-Xi , Cai Meng-Ting , He Ming-Xia , Lu Yu-Qiang , Luo Xiao , Zhang Tian-Yi
Published: May 2022

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune-mediated idiopathic inflammatory demyelinating disease with a typical clinical presentation of optic neuritis, acute myelitis, and area postrema syndrome. Most NMOSD patients are seropositive for disease-specific and pathogenic aquaporin-4 (AQP4) antibodies, which are key markers for the NMOSD diagnosis. Herein, we report an atypical case of a 41-year-old man who complained of intractable hiccups and vomiting at disease onset, followed by fever, headache, back pain, progressive paresthesia, and weakness of extremities later on. Magnetic resonance imaging revealed longitudinally extensive transverse myelitis. Cerebrospinal fluid analysis showed progressive increases in the white blood cell count and the protein level, which were accompanied by the deterioration of clinical manifestations. The patient was initially suspected of infectious meningomyelitis but was finally diagnosed with NMOSD. This case with distinct cerebrospinal fluid findings broadens the phenotypic spectrum of NMOSD. Furthermore, it also highlights the clinical value of AQP4 antibody test for early definitive diagnosis and proper treatment.
Targeting Glutamine Metabolism Ameliorates Autoimmune Hepatitis via Inhibiting T Cell Activation and Differentiation
Authors: Yu Qiang , Tu Honghu , Yin Xueyi , Peng Chang , Dou Chuanyun , Yang Wenhua , Wu Wenbiao , Guan Xiaotong , Li Jia , Yan Hexin , Zang Yi , Jiang Haowen , Xia Qiang
Published: May 2022

Background

Autoimmune hepatitis (AIH) is mediated by a cascade of T cell-mediated events directed at liver cells and persistent inflammation within the liver can eventually result in liver cirrhosis. Targeting glutamine metabolism has an impact on T cell activation and differentiation. However, the effect of glutamine metabolism blocking upon AIH remains unknown. We use glutaminase antagonist 6-diazo-5-oxo-L-norleucine (DON) for in vitro assays and its prodrug 2-(2-amino-4-methylpentanamido)-DON (JHU083) for in vivo assays to investigate the potential therapeutic effect and molecular mechanism of glutamine metabolism blocking in an AIH murine model.

Methods

AIH mice were treated with JHU083 or vehicle before concanavalin A (ConA) administration, and disease severity was examined. Then activation and differentiation [including Th1/Th17 cells and cytotoxic T lymphocytes (CTL)] of T cells from Vehicle-WT, JHU083-AIH and Vehicle-AIH mice were tested. Furthermore, in vitro T cell activation and differentiation were measured using separated splenocytes stimulated with ConA with or without DON. The activation and differentiation of T cells were tested using flow cytometry, qRT-PCR and ELISA. Phosphorylation level of mammalian target of rapamycin (mTOR) and 70 kDa ribosomal protein S6 kinase (P70S6K) were examined by western blotting.

Results

JHU083 and DON significantly suppressed the activation of T cells and inhibited the differentiation of Th1/Th17 cells and CTL in vivo and in vitro. Besides, we demonstrated that glutamine metabolism blocking inhibited T cells activation and differentiation through decreasing the mRNA expression of amino acid transporter solute carrier family 7 member 5 (SLC7A5) and mitigating the activation of mTOR signaling.

Conclusions

We proved that targeting glutamine metabolism represents a potential new treatment strategy for patients with AIH and other T cell-mediated disease. Mechanistically, we demonstrated that glutamine metabolism blocking inhibits T cells activation and suppresses the differentiation of Th1/Th17 cells and CTL.
Cyclone Impacts on Coral Reef Communities in Southwest Madagascar
Authors: Carter Amber L. , Gilchrist Hannah , Dexter Kyle G. , Gardner Charlie J. , Gough Charlotte , Rocliffe Steve , Wilson A. Meriwether W.
Published: May 2022

Tropical cyclones can cause severe destruction of coral reefs with ecological consequences for reef fish communities. Ocean warming is predicted to shorten the return interval for strong tropical cyclones. Understanding the consequences of cyclone impacts on coral reefs is critical to inform local-scale management to support reef resilience and the livelihood security of small-scale fishing communities. Here, we present the first analysis of a tropical cyclone disturbance on coral reefs in Madagascar. We investigate the impact of Cyclone Haruna (category 3 Saffir-Simpson scale) in February 2013 on coral communities, both adults and recruits, and explore the relationship between the severity of cyclone impact with cyclone parameters (wind speed, duration of storm impact and distance from cyclone track) and environmental variables (reef type and reef depth). We use survey data collected as part of a long-term citizen science monitoring programme at 21 coral reef sites between 2012 and 2015 in the Velondriake Locally Managed Marine Area along Madagascar’s southwest coast. Coral cover declined at 19 sites, however damage was spatially heterogeneous ranging from a decrease in coral cover of 1.4% to 45.8%. We found the severity of cyclone damage related to: distance from the cyclone track, duration of cyclone impact and reef depth. The taxonomic and morphological composition of coral communities was significantly different after the cyclone. Notably, there was a decrease in the dominance of branching morphologies, and an increase in the relative abundance of encrusting and massive morphologies. Two years after Cyclone Haruna, mean coral cover had increased and the density of coral recruits increased to above pre-cyclone levels indicating the potential recovery of coral populations. However, recovery to pre-disturbance community composition will likely be hindered by the increasing occurrence of acute and chronic disturbance events.
Carbon Assimilation by the Picoplanktonic Community Inhabiting the Secondary Chlorophyll Maximum of the Anoxic Marine Zones of the Eastern Tropical North and South Pacific
Authors: Aldunate Montserrat , von Dassow Peter , Vargas Cristian A. , Ulloa Osvaldo
Published: May 2022

Anoxic marine zones (AMZs) constitute pelagic systems distinguished from the oxygen minimum zones (OMZs) by the complete absence of detectable oxygen and the accumulation of nitrite in mid-waters. At the top of the oxygen-depleted layer and below the oxycline, nutrients are abundant; light intensity is very much reduced (<1% of incident light) and a secondary chlorophyll maximum (SCM) is developed. The shoaling of the oxygen-depleted layer, product of the AMZ expansion, could enhance this SCM, which has little-known biogeochemical effects. Here, we show that the SCM is contributing a measurable signal in the particulate organic carbon (POC), enough to alter the δ13CPOC in the top of the oxygen-depleted layer. This data showed significant differences among stations with and without the development of a SCM, being 3.0‰ heavier when a SCM is developed, and indicating photosynthetic activity and/or remineralization in the top of the AMZ. More depleted δ13CPOC values were also found when no SCM was present indicating stronger chemoautotrophic activity, potentially driven by anammox and sulfur-oxidizing bacteria activity. Assimilation rate data show that when sufficient light and Prochlorococcus are present, photosynthesis exceeds chemoautotrophic carbon fixation, and can exceed heterotrophic assimilation of glucose or acetate. However, in the majority of the stations, assimilation rates of both glucose and acetate exceeded carbon fixation rates under light stimulation, suggesting that often the SCM is still a net heterotrophic system.