bluuebunny/crossref_metadata_2025 huggingface dataset:
β-arrestin1-E2F1-ac axis regulates physiological apoptosis and cell cycle exit in cellular models of early postnatal cerebellum
Authors: Abballe Luana , Alfano Vincenzo , Antonacci Celeste , Cefalo Maria Giuseppina , Cacchione Antonella , Del Baldo Giada , Pezzullo Marco , Po Agnese , Moretti Marta , Mastronuzzi Angela , De Smaele Enrico , Ferretti Elisabetta , Locatelli Franco , Miele Evelina
Published: February 2023

Development of the cerebellum is characterized by rapid proliferation of cerebellar granule cell precursors (GCPs) induced by paracrine stimulation of Sonic hedgehog (Shh) signaling from Purkinje cells, in the external granular layer (EGL). Then, granule cell precursors differentiate and migrate into the inner granular layer (IGL) of the cerebellum to form a terminally differentiated cell compartment. Aberrant activation of Sonic hedgehog signaling leads to granule cell precursors hyperproliferation and the onset of Sonic hedgehog medulloblastoma (MB), the most common embryonal brain tumor. β-arrestin1 (ARRB1) protein plays an important role downstream of Smoothened, a component of the Sonic hedgehog pathway. In the medulloblastoma context, β-arrestin1 is involved in a regulatory axis in association with the acetyltransferase P300, leading to the acetylated form of the transcription factor E2F1 (E2F1-ac) and redirecting its activity toward pro-apoptotic gene targets. This axis in the granule cell precursors physiological context has not been investigated yet. In this study, we demonstrate that β-arrestin1 has antiproliferative and pro-apoptotic functions in cerebellar development. β-arrestin1 silencing increases proliferation of Sonic hedgehog treated-cerebellar precursor cells while decreases the transcription of E2F1-ac pro-apoptotic targets genes, thus impairing apoptosis. Indeed, chromatin immunoprecipitation experiments show a direct interaction between β-arrestin1 and the promoter regions of the pro-apoptotic E2F1 target gene and P27, indicating the double role of β-arrestin1 in controlling apoptosis and cell cycle exit in a physiological context. Our data elucidate the role of β-arrestin1 in the early postnatal stages of cerebellar development, in those cell compartments that give rise to medulloblastoma. This series of experiments suggests that the physiological function of β-arrestin1 in neuronal progenitors is to directly control, cooperating with E2F1 acetylated form, transcription of pro-apoptotic genes.
A kitchen experiment for replicating lava-ice interaction on stratovolcanoes
Authors: Conway Chris E. , Tani Kenichiro , Sano Takashi , Matsumoto Keiko , Ishizuka Osamu
Published: February 2023

Many Quaternary stratovolcanoes host (or hosted) glacial ice with volumes that have fluctuated in response to long-term global climate cycles. The repeated advance and retreat of ice in valleys on the flanks of volcanoes throughout their eruptive histories has impacted how and where lava flows are emplaced and preserved. Understanding the dynamics of lava-ice interaction is a vital part of reconstructing the growth histories of many stratovolcanoes and can provide valuable clues about the evolution of Earth’s climate. We have constructed a basic experiment, using common kitchen ingredients and utensils, to replicate the interaction between lava flows and glaciers on stratovolcanoes. This article outlines the ingredients and recipes for soda bread (stratovolcano analogy), ice cream (glacier analogies), and sauce (lava flow analogies), and describes exercises that provide qualitative lessons about the morphology of volcanoes, natural hazards, and paleoclimate. As such, the experiment can be used in geoscience outreach demonstrations for students and will assist non-specialist scientists with undertaking field identification of ice-bounded lava flows.
Contribution of vanishing mountain glaciers to global and regional terrestrial water storage changes
Authors: Li Xiuping , Wang Lei , Hu Baoyi , Chen Deliang , Liu Ruishun
Published: February 2023

Mountain is called the water towers of the world. Due to high sensitivity and vulnerability to climate change, more attention is paid to the change of water resources in mountain regions, where provide water for environmental and human demands downstream. Mountains glacier, as one of the most important components of terrestrial water storage (TWS), effectively regulates and stabilizes surface water resources. TWS appears to be trending below previous ranges in recent years, and glacier retreating is becoming the primary cause of TWS depletion in mountain regions. However, how much mountain glacier changes contribute to TWS changes around mountain regions is unknown. Here, we combine multi-source datasets to quantify the contribution rate over high-elevation mountain regions. On a global scale, the glacial melting is equivalent to about 49% of the total TWS decline during 2006–2015. TWS and glacier show decreasing trends in most of mountain regions and watersheds of the Third Pole and surroundings (TPs), but the contribution ranges from −23% to 728% in mountain regions and −21% to 99% in watersheds of TPs. There are larger contributions in regions with more glaciers, while smaller in less glacier-covered regions. Glacier together with other storage components play diverse roles across different mountain regions and watersheds, but factors with great influence are glacier, groundwater, soil water, reservoirs and lakes.
Modulation of vulvovaginal atrophy (VVA) by Gelam honey in bilateral oophorectomized rats
Authors: Ismail Nur Hilwani , Ibrahim Siti Fatimah , Mokhtar Mohd Helmy , Yahaya Azyani , Zulkefli Aini Farzana , Ankasha Sheril June , Osman Khairul
Published: February 2023

Introduction

Vulvovaginal atrophy (VVA) is a common condition in post-menopausal women. Symptoms of VVA include dyspareunia, vaginal dryness, vaginal and/or vulvar itching, burning and soreness, dysuria and vaginal bleeding accompanying sexual activity. These symptoms are physiological responses to hypoestrogenicity, inducing atrophy of the vagina epithelia and sudden reduction in mucous production. Prevailing therapy for VVA is hormone replacement therapy (HRT), notably estrogen, progesterone or a combination of the two. However, using HRT is associated with an increased incidence of breast and endometrial cancer, venous thromboembolism in the lungs and legs, stroke and cardiovascular complications.

Methods

This study evaluated Malaysian Gelam honey as a nutraceutical alternative to estrogen HRT (ERT) in alleviating VVA. A total of 24 female 8-weekold Sprague Dawley rats underwent bilateral oophorectomy. A minimum of 14 days elapsed from the time of surgery and administration of the first dose of Gelam honey to allow the female hormones to subside to a stable baseline and complete recovery from surgery. Vaginal tissues were harvested following a 2-week administration of Gelam honey, the harvested vagina tissue underwent immunohistochemistry (IHC) analysis for protein localization and qPCR for mRNA expression analysis.

Results

Results indicated that Gelam honey administration had increased the localization of Aqp1, Aqp5, CFTR and Muc1 proteins in vaginal tissue compared to the menopause group. The effect of Gelam honey on the protein expressions is summarized as Aqp1>CFTR>Aqp5>Muc1.

Discussion

Gene expression analysis reveals Gelam honey had no effect on Aqp1 and CFTR genes. Gelam honey had up-regulated Aqp5 gene expression. However, its expression was lower than in the ERT+Ovx group. Additionally, Gelam honey up-regulated Muc1 in the vagina, with an expression level higher than those observed either in the ERT+Ovx or SC groups. Gelam honey exhibits a weak estrogenic effect on the genes and proteins responsible for regulating water in the vaginal tissue (Aqp1, Aqp5 and CFTR). In contrast, Gelam honey exhibits a strong estrogenic ability in influencing gene and protein expression for the sialic acid Muc1. Muc1 is associated with mucous production at the vaginal epithelial layer. In conclusion, the protein and gene expression changes in the vagina by Gelam honey had reduced the occurrence of vaginal atrophy in surgically-induced menopause models.
A novel prognostic model for patients with colon adenocarcinoma
Authors: Yin Chengliang , Wang Wanling , Cao Wenzhe , Chen Yuanyuan , Sun Xiaochun , He Kunlun
Published: February 2023

Background

Colon adenocarcinoma (COAD) is a highly heterogeneous disease, which makes its prognostic prediction challenging. The purpose of this study was to investigate the clinical epidemiological characteristics, prognostic factors, and survival outcomes of patients with COAD in order to establish and validate a predictive clinical model (nomogram) for these patients.

Methods

Using the SEER (Surveillance, Epidemiology, and End Results) database, we identified patients diagnosed with COAD between 1983 and 2015. Disease-specific survival (DSS) and overall survival (OS) were assessed using the log-rank test and Kaplan–Meier approach. Univariate and multivariate analyses were performed using Cox regression, which identified the independent prognostic factors for OS and DSS. The nomograms constructed to predict OS were based on these independent prognostic factors. The predictive ability of the nomograms was assessed using receiver operating characteristic (ROC) curves and calibration plots, while accuracy was assessed using decision curve analysis (DCA). Clinical utility was evaluated with a clinical impact curve (CIC).

Results

A total of 104,933 patients were identified to have COAD, including 31,479 women and 73,454 men. The follow-up study duration ranged from 22 to 88 months, with an average of 46 months. Multivariate Cox regression analysis revealed that age, gender, race, site_recode_ICD, grade, CS_tumor_size, CS_extension, and metastasis were independent prognostic factors. Nomograms were constructed to predict the probability of 1-, 3-, and 5-year OS and DSS. The concordance index (C-index) and calibration plots showed that the established nomograms had robust predictive ability. The clinical decision chart (from the DCA) and the clinical impact chart (from the CIC) showed good predictive accuracy and clinical utility.

Conclusion

In this study, a nomogram model for predicting the individualized survival probability of patients with COAD was constructed and validated. The nomograms of patients with COAD were accurate for predicting the 1-, 3-, and 5-year DSS. This study has great significance for clinical treatments. It also provides guidance for further prospective follow-up studies.
A non-intrusive load decomposition method of resident by multi-scale attention mechanism
Authors: Dai Jiejie , Xie Jing , Huang Chuan , Wu Bin , Li Hantang , Ma Yuan , Li Shilong
Published: February 2023

Non-intrusive load monitoring (NILM) is one of the important technologies in home energy management and power demand response scenario. However, the presence of multi-mode appliances and appliances with close power values have affected in diminishing the accuracy of identification based NILM algorithms. To tackle these challenges, the work proposes a resident load decomposition method combining multi-scale attention mechanism and convolutional neural network. At the first stage, the attention scores of the normal load data at the previous few moments of the attention model are smoothed dynamically against the abnormal scores at the current moment. The load identification attention model is optimized by constraint factors. Then, on this basis, convolution filters of different sizes are used to model the mixed load data of different electrical equipment, to mine more abundant characteristic information. Finally, to illustrate the proposed processes and validate its effectiveness, taking the PLAID data set as an example, the method proposed in the article is compared with respect to the existing NILM techniques. The experimental results show that the method based on the multi-scale attention mechanism in this paper can greatly improve the effect of load decomposition. Moreover, it reduces the confusion problem of electrical appliance identification with similar load characteristics.
Sustainable development efficiency and its influencing factors across BRICS and G7 countries: An empirical comparison
Authors: Cheng Shixiong , Addis Amsalu K. , Chen Lipeng , Zhu Zuping
Published: February 2023

Sustainable development is the global overarching paradigm and essential for achieving economic, social, and environmental development. The primary goal of this study is to compare the efficiency of sustainable development and evaluate its influencing factors across the BRICS (Brazil, Russia, India, China, and South Africa) and G7 (Canada, France, Germany, Italy, Japan, the United Kingdom, and United States) countries by examining total factor productivity, efficiency change, and technological change. For this, we adopted the super-efficiency SBM-DEA model with undesirable output and Global Malmquist-Luenberger (GML) productivity index model to overcome inaccurate efficiency results while avoiding environmentally unwanted outputs and to resolve the shortcomings of the conventional Malmquist-Luenberger index. It is also necessary to explore relevant influencing factors on the environmental pollution thereby affects the sustainable development efficiency of the study countries, thus, this study employed STIRPAT approach. A panel data of BRICS and G7 countries from 2005 to 2015 is used. The findings reveal that sustainable total factor productivity (GML) in China (1.0165), the US (1.0150), and UK (1.0024) is on the rise. China is also one of the countries that experienced the highest positive efficiency change (GMLEC) (1.0147) and the US has the highest positive technical change (GMLTC) (1.0103). Contrarily, Russia experienced the highest decline in GMLTC (0.9316) as well as GML indexes (0.9337), whereas South Africa experienced the highest decline in GMLEC (0.9707). Additionally, GDP per capita (.0969) and population (.4178) have a positive influence on CO2 emissions in the BRICS countries, whereas in the G7 nations, GDP per capita (−.2180) and population (−.1249) have negative influences on CO2 emissions. The study also offers practical recommendations to address identified limitations and improve sustainable productivity and environmental efficiency. The inverse link between GDP and CO2 emissions might imply that the G7 nations have passed the turning point on an environmental Kuznets curve (EKC), but this finding does not support the EKC hypothesis in the BRICS nations.
Fatigue assessment of flange connections in offshore wind turbines under the initial flatness divergence
Authors: Ji Xingda , Zou Tao , Bai Xu , Niu Xinbo , Tao Longbin
Published: February 2023

Bolted ring flange connections are widely utilized in offshore wind turbines to connect steel tubular segments. After the massive production and installation of offshore wind turbines in the past decade, flatness divergence is regarded as one of the most important initial imperfections for the fatigue design of flange connections. Offshore wind turbines are subjected to wind, wave, and current loads. This initial imperfection may alter the structural response and accelerate the fatigue crack growth. This paper aims to analyse the impact of the initial flatness divergence on the structural response of flange connections and evaluate its consequences on fatigue damage. Two different offshore wind turbines with fixed foundations and floating foundations are modelled to simulate their global responses to environmental loads. Based on a superposition method, local finite-element models of flange connections are established with three types of flatness divergence. Using the same bolt pretension and external loads from global modelling, the impact of these geometric imperfections is further examined by comparing the structural responses of flanges under different radial and peripheral opening lengths. Then, the fatigue assessments on flange connections in both fixed wind turbines and floating wind turbines are conducted, and the impacts of initial flatness divergence on these two different wind turbines are analysed.
Impacts of water scarcity on agricultural production and electricity generation in the Middle East and North Africa
Authors: Hejazi Mohamad , Santos Da Silva Silvia R. , Miralles-Wilhelm Fernando , Kim Son , Kyle Page , Liu Yaling , Vernon Chris , Delgado Alison , Edmonds Jae , Clarke Leon
Published: February 2023

Incorporating the interdependencies between water, energy and food (WEF) within an integrated approach of planning and management could help nations worldwide to address sustainability concerns. This is a topic of great importance for the Middle East and North Africa (MENA) region, where water is a very limited resource. In this study, we develop an analytical framework to analyze the water-energy-food nexus in the MENA region to inform the formulation of integrated strategies for water, energy and food activities. Our approach is based on an integrated assessment model for the MENA region, which explicitly represents WEF sectors within an economic framework, in tandem with a set of relevant scenarios addressing three key dimensions (socioeconomics, climate and water-management). Using this framework, our study analyzes the current and projected status of water resources in the region, and the potential implications for the agriculture and electricity sectors. Our scenarios demonstrate that water scarcity worsens by the end of the 21st century in most MENA countries, mostly due to growing demands. The impacts of growing scarcity on agriculture are significant, with production projected to drop by 60 percent by 2050 in some countries. On the other hand, and to a lesser extent, water-saving technologies and fuel-switching in the power sector play a key role in mitigating the effects of water scarcity on electricity generation in some parts of the MENA region. Our analysis then underscores the need to reduce the dependence of MENA’s agricultural and energy sectors on water, and transition to renewable energies to reduce water scarcity.
Estimating the potential drivers of dispersal outcomes for juvenile gopher frogs (Rana capito) using agent-based models
Authors: Burrow Angela K. , McEntire Kira D. , Maerz John C.
Published: February 2023

Among mobile terrestrial animals, movement among microsites can allow individuals to behaviorally moderate their body temperatures and rates of water loss, which can have important consequences for activity times, growth, fecundity, and survival. Ground-layer vegetation can change the availability and variability of microclimates; however, gaps in our understanding of how individuals interact with the microclimates created by vegetation limit our ability to inform management actions for wildlife. Amphibians can simultaneously balance operant body temperatures and water loss and the availability of heterogeneous microclimates should moderate how effectively they are able to do so. However, relatively few studies have attempted to mechanistically demonstrate how ground vegetation-driven effects on microclimatic variation may affect amphibian performance and survival. Agent-based modeling (ABM) can incorporate behavior and other mechanisms to understand how animals interact with their environments to result in larger scale patterns. They are effective for exploring alternative scenarios and representing the uncertainty in systems. Here, we use ABMs to integrate field and laboratory measurements of movement behavior, physiology, and plant effects on near-ground microclimate to explore how ground vegetation and the availability of terrestrial refugia may affect the survival and terrestrial distributions of juvenile gopher frogs (Rana capito) under two weather regimes. We also examine how assumptions regarding micro-scale movement (< 1 m2) affect the influence of ground vegetation on survival and settlement within refugia. While all variables affected settlement and survival, our models predict that inter-annual variation in weather and the density and spatial distribution of permanent refugia likely have the greatest influence on juvenile survival. The benefit of increased ground vegetation was dependent on the reasonable assumption that gopher frogs exhibit microclimate habitat selection throughout the day and night to limit water loss. Our models suggest that vegetation would be most beneficial to amphibians under warmer weather regimes provided there is sufficient rainfall.
Advanced biorefinery feedstock from non-recyclable municipal solid waste by mechanical preprocessing
Authors: Saha Nepu , Klinger Jordan , Islam Md Tahmid , Reza Toufiq
Published: February 2023

Because of accelerated urbanization and the development of a global economy, a large quantity of municipal solid waste (MSW) has been collected and disposed of by the municipalities. Due to this drastic increase in the disposal of MSW, the need for its management is a must to preserve the environment. Currently, approximately 50% of the total MSW generated in the United States has been utilized through various recycling, combustion, and composting technologies, which means the remaining 50% is sent to landfill; this is often known as non-recyclable MSW (nMSW). As this nMSW is physically and chemically heterogenous and contains very high amounts of inorganic material, processing is required prior to using it as a biorefinery feedstock. Thus, this study focused on how mechanical preprocessing advanced the physical and chemical properties of nMSW. The physical and chemical properties were investigated in terms of particle size distribution, bulk density, ultimate and proximate analysis, and the higher heating value (HHV). The combustion properties were examined in terms of ignition temperature, peak heat release rate, and combustion efficiency. Results showed that the variability of physical and chemical properties of nMSW can be reduced by mechanical preprocessing. For example, the variability of the bulk density of the as-received nMSW was approximately 17.3% while it reduced to 5.8% when the sample size was reduced to 2 mm. Similarly, the variability of ash and HHV reduced from 49.2% to 11.0% and 13.4%–4.2%, respectively. Combustion thermograms showed that the size reduction positively improved the combustion properties. For example, 2 mm of spec sample started to ignite approximately 4 times earlier and took 6.5 folds less time to reach the peak heating rate compared to as-received nMSW. Overall, the mechanical preprocessing reduced the variability of physical and chemical properties in addition to the improvement of combustion behavior of the nMSW which is one step forward toward the biorefinery feedstock.
Exome sequencing in fetuses with short long bones detected by ultrasonography: A retrospective cohort study
Authors: Huang Yanlin , Liu Chang , Ding Hongke , Wang Yunan , Yu Lihua , Guo Fangfang , Li Fake , Shi Xiaomei , Zhang Yan , Yin Aihua
Published: February 2023

Background: Prenatal diagnosis of fetal short long bones (SLBs) was reported to be associated with skeletal dysplasias, chromosomal abnormalities, and genetic syndromes. This study aims to identify the genetic causes for fetal short long bones, and retrospectively evaluate the additional diagnostic yield of exome sequencing (ES) for short long bones following the use of conventional genetic testing.

Methods: A cohort of ninety-four fetuses with sonographically identified short long bones was analyzed by trio-exome sequencing between January 2016 and June 2021. Fetuses with abnormal results of karyotype or chromosomal microarray analysis were excluded. Variants were interpreted based on ACMG/AMP guidelines. All diagnostic de novo variants were validated by Sanger sequencing.

Results: Of the 94 fetuses, 38 (40.4%) were found to carry causal genetic variants (pathogenic or likely pathogenic) in sixteen genes with 38 variants. Five fetuses (5.3%) had variant(s) of uncertain significance. Thirty-five cases (37.2%) were diagnosed as genetic skeletal dysplasias including 14 different diseases that were classified into 10 groups according to the Nosology and Classification of Genetic Skeletal Disorders. The most common disease in the cohort was achondroplasia (28.9%), followed by osteogenesis imperfecta (18.4%), thanatophoric dysplasia (10.5%), chondrogenesis (7.9%), and 3-M syndrome (5.3%). The diagnostic yield in fetuses with isolated short long bones was lower than the fetuses with non-isolated short long bones, but not reached statistical significance (27.3% vs. 44.4%; p = 0.151). Whereas, the rate in the fetuses with other skeletal abnormalities was significantly higher than those with non-skeletal abnormalities (59.4% vs. 32.5%, p = 0.023), and the diagnostic rate was significantly higher in femur length (FL) below -4SDs group compared with FL 2-4SDs below GA group (72.5% vs. 16.7%; p < 0.001). A long-term follow-up showed that outcomes for fetuses with FL 2-4SDs below GA were significantly better than those with FL below -4SDs. Additionally, fourteen (36.8%) novel short long bones-related variants were identified in the present study.

Conclusion: The findings suggest that in fetuses with short long bones routine genetic tests failed to determine the underlying causes, exome sequencing could add clinically relevant information that could assist the clinical management of pregnancies. Novel pathogenic variants identified may broaden the mutation spectrum for the disorders and contributes to clinical consultation and subsequent pregnancy examination.
Population structure and evolutionary history of the greater cane rat (Thryonomys swinderianus) from the Guinean Forests of West Africa
Authors: Babarinde Isaac A. , Adeola Adeniyi C. , Djagoun Chabi A. M. S. , Nneji Lotanna M. , Okeyoyin Agboola O. , Niba George , Wanzie Ndifor K. , Oladipo Ojo C. , Adebambo Ayotunde O. , Bello Semiu F. , Ng’ang’a Said I. , Olaniyi Wasiu A. , Okoro Victor M. O. , Adedeji Babatunde E. , Olatunde Omotoso , Ayoola Adeola O. , Matouke Moise M. , Wang Yun-yu , Sanke Oscar J. , Oseni Saidu O. , Nwani Christopher D. , Murphy Robert W.
Published: February 2023

Grasscutter (Thryonomys swinderianus) is a large-body old world rodent found in sub-Saharan Africa. The body size and the unique taste of the meat of this major crop pest have made it a target of intense hunting and a potential consideration as a micro-livestock. However, there is insufficient knowledge on the genetic diversity of its populations across African Guinean forests. Herein, we investigated the genetic diversity, population structures and evolutionary history of seven Nigerian wild grasscutter populations together with individuals from Cameroon, Republic of Benin, and Ghana, using five mitochondrial fragments, including D-loop and cytochrome b (CYTB). D-loop haplotype diversity ranged from 0.571 (± 0.149) in Republic of Benin to 0.921 (± 0.013) in Ghana. Within Nigeria, the haplotype diversity ranged from 0.659 (± 0.059) in Cross River to 0.837 (± 0.075) in Ondo subpopulation. The fixation index (FST), haplotype frequency distribution and analysis of molecular variance revealed varying levels of population structures across populations. No significant signature of population contraction was detected in the grasscutter populations. Evolutionary analyses of CYTB suggests that South African population might have diverged from other populations about 6.1 (2.6–10.18, 95% CI) MYA. Taken together, this study reveals the population status and evolutionary history of grasscutter populations in the region.
B cell-activating factor (BAFF) from dendritic cells, monocytes and neutrophils is required for B cell maturation and autoantibody production in SLE-like autoimmune disease
Authors: Giordano Daniela , Kuley Runa , Draves Kevin E. , Elkon Keith B. , Giltiay Natalia V. , Clark Edward A.
Published: February 2023

Purpose and methods

B cell-activating factor (BAFF) contributes to the pathogenesis of autoimmune diseases including systemic lupus erythematosus (SLE). Although several anti-BAFF Abs and derivatives have been developed for the treatment of SLE, the specific sources of BAFF that sustain autoantibody (auto-Ab) producing cells have not been definitively identified. Using BAFF-RFP reporter mice, we identified major changes in BAFF-producing cells in two mouse spontaneous lupus models (Tlr7 Tg mice and Sle1), and in a pristane-induced lupus (PIL) model.

Results

First, we confirmed that similar to their wildtype Tlr7 Tg and Sle1 mice counterparts, BAFF-RFP Tlr7 Tg mice and BAFF-RFP Sle1 mice had increased BAFF serum levels, which correlated with increases in plasma cells and auto-Ab production. Next, using the RFP reporter, we defined which cells had dysregulated BAFF production. BAFF-producing neutrophils (Nphs), monocytes (MOs), cDCs, T cells and B cells were all expanded in the spleens of BAFF-RFP Tlr7 Tg mice and BAFF-RFP Sle1 mice compared to controls. Furthermore, Ly6Chi inflammatory MOs and T cells had significantly increased BAFF expression per cell in both spontaneous lupus models, while CD8- DCs up-regulated BAFF expression only in the Tlr7 Tg mice. Similarly, pristane injection of BAFF-RFP mice induced increases in serum BAFF levels, auto-Abs, and the expansion of BAFF-producing Nphs, MOs, and DCs in both the spleen and peritoneal cavity. BAFF expression in MOs and DCs, in contrast to BAFF from Nphs, was required to maintain homeostatic and pristane-induced systemic BAFF levels and to sustain mature B cell pools in spleens and BMs. Although acting through different mechanisms, Nph, MO and DC sources of BAFF were each required for the development of auto-Abs in PIL mice.

Conclusions

Our findings underscore the importance of considering the relative roles of specific myeloid BAFF sources and B cell niches when developing treatments for SLE and other BAFF-associated autoimmune diseases.
Pan-cancer analysis reveals potential of FAM110A as a prognostic and immunological biomarker in human cancer
Authors: Zhong Hongguang , Shi Qianqian , Wen Qin , Chen Jingyi , Li Xuan , Ruan Ruiwen , Zeng Shaocheng , Dai Xiaofeng , Xiong Jianping , Li Li , Lei Wan , Deng Jun
Published: February 2023

Background

Despite great success, immunotherapy still faces many challenges in practical applications. It was previously found that family with sequence similarity 110 member A (FAM110A) participate in the regulation of the cell cycle and plays an oncogenic role in pancreatic cancer. However, the prognostic value of FAM110A in pan-cancer and its involvement in immune response remain unclear.

Methods

The Human Protein Atlas (HPA) database was used to detect the expression of FAM110A in human normal tissues, the Tumor Immune Estimation Resource (TIMER) and TIMER 2.0 databases were used to explore the association of FAM110A expression with immune checkpoint genes and immune infiltration, and the Gene Set Cancer Analysis (GSCA) database was used to explore the correlation between FAM110A expression and copy number variations (CNV) and methylation. The LinkedOmics database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Statistical analysis and visualization of data from the The Cancer Genome Atlas (TCGA) or the Genotype–Tissue Expression (GTEx) databases were performed using the R software (version 3.6.3). Clinical samples were validated using immunohistochemistry.

Results

FAM110A expression was elevated in most tumor tissues compared with that in normal tissues. CNV and methylation were associated with abnormal FAM110A mRNA expression in tumor tissues. FAM110A affected prognosis and was associated with the expression of multiple immune checkpoint genes and abundance of tumor-infiltrating immune cells across multiple types of cancer, especially in liver hepatocellular carcinoma (LIHC). FAM110A-related genes were involved in multiple immune-related processes in LIHC.

Conclusion

FAM110A participates in regulating the immune infiltration and affecting the prognosis of patients in multiple cancers, especially in LIHC. FAM110A may serve as a prognostic and immunological biomarker for human cancer.
The STING/TBK1/IRF3/IFN type I pathway is defective in cystic fibrosis
Authors: Occhigrossi Luca , Rossin Federica , Villella Valeria Rachela , Esposito Speranza , Abbate Carlo , D’Eletto Manuela , Farrace Maria Grazia , Tosco Antonella , Nardacci Roberta , Fimia Gian Maria , Raia Valeria , Piacentini Mauro
Published: February 2023

Cystic fibrosis (CF) is a rare autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The most common mutation is F508del-CFTR (ΔF) which leads the encoded ion channel towards misfolding and premature degradation. The disease is characterized by chronic bronchopulmonary obstruction, inflammation and airways colonization by bacteria, which are the major cause of morbidity and mortality. The STING pathway is the main signaling route activated in the presence of both self and pathogen DNA, leading to Type I Interferon (IFN I) production and the innate immune response. In this study, we show for the first time the relationship existing in CF between resistant and recurrent opportunistic infections by Pseudomonas aeruginosa and the innate immunity impairment. We demonstrate through ex vivo and in vivo experiments that the pathway is inadequately activated in ΔF condition and the use of direct STING agonists, as 2′,3′-cyclic GMP-AMP (2’, 3’ cGAMP), is able to restore the immune response against bacterial colonization. Indeed, upon treatment with the STING pathway agonists, we found a reduction of colony forming units (CFUs) consequent to IFN-β enhanced production in Pseudomonas aeruginosa infected bone marrow derived macrophages and lung tissues from mice affected by Cystic Fibrosis. Importantly, we also verified that the impairment detected in the primary PBMCs obtained from ΔF patients can be corrected by 2’, 3’ cGAMP. Our work indicates that the cGAS/STING pathway integrity is crucial in the Cystic Fibrosis response against pathogens and that the restoration of the pathway by 2’, 3’ cGAMP could be exploited as a possible new target for the symptomatic treatment of the disease.
Antimicrobial skin peptides in premature infants: Comparison with term infants and impact of perinatal factors
Authors: Humberg Alexander , Neuenburg Lisa , Boeckel Hannah , Fortmann Mats Ingmar , Härtel Christoph , Herting Egbert , Hinrichs Heilwig , Rademacher Franziska , Harder Jürgen
Published: February 2023

Introduction

Preterm infants have an immature epidermis barrier function that may lead to an increased permeability to pathogens. On the surface of the human skin, antimicrobial peptides (AMPs) are important molecules of the innate immune system, have broad antimicrobial properties, and provide an essential role in integrity of the microbiome. Given the marked susceptibility of preterm infants to infection, we hypothesize a decreased expression of AMPs on the skin of preterm infants.

Materials and methods

In a prospective single-center study with 35 preterm and 20 term infants, we analyzed skin rinsing probes for the presence of the AMPs psoriasin (S100A7) and ribonuclease 7 (RNase 7) via enzyme-linked immunosorbent assay. Samples were taken from preterm infants < 34 0/7 weeks gestational age (mean ± SD gestational age, 28.8 ± 2.4 weeks) on days 0, 7, 14, and 28 after birth. Term infants (> 36 6/7 weeks) (controls) were washed on days 0 and 28.

Results

Psoriasin and RNase 7 were both expressed on skin of preterm and term infants and increased in concentration significantly over time. RNase 7 was more expressed in term infants on day 0 [preterm = 1.1 (0.7–2.9) vs. term = 2.0 (1.1–3.4) ng/ml, p = 0.017]. On day 28, premature infants showed higher values of psoriasin [preterm = 10.9 (5.6–14.2) vs. term = 6.3 (3.4–9.0) ng/ml, p < 0.001]. Notably, preterm infants with infectious or inflammatory context driven by histological proof of chorioamnionitis and early-onset or late-onset sepsis had higher concentrations of psoriasin as compared with non-affected preterm infants. After exclusion of infants with inflammatory hit, median concentrations of RNase 7 and psoriasin did not differ between preterm and full-term infants on days 0 and 28.

Discussion

Psoriasin and RNase 7 concentrations increase over time on the skin of newborn infants and seem to play a role in the first defense against infection. This is of particularly interest as the role of AMPs on a maturing skin microbiome and its possible new prevention strategies is unclear and needs to be determined.
Nutrients and rheumatoid arthritis: From the perspective of neutrophils
Authors: Shao Ya-Ru , Xu Dan-Yi , Lin Jin
Published: February 2023

Neutrophils are considered as core immune cells involve in the early stage of rheumatoid arthritis (RA) and participate in the disease progression. The underlining mechanisms include the elevated chemotaxis and infiltration of neutrophils, the increase in the reactive oxygen species and the promotion of neutrophil extracellular traps formation. Accumulating studies demonstrated the important role of nutrients intake played in the initiation and progression of RA. This study summarized the effects of several macronutrients and micronutrients on regulating RA through the modulation of activated neutrophils and appealed for a healthy diet in RA-risk individuals as well as RA patients.
The development of highly dense highly protected surfactant ionizable lipid RNA loaded nanoparticles
Authors: González-Rioja Ramon , Salazar Vivian A. , Bastús Neus G. , Puntes Victor
Published: February 2023

The long quest for efficient drug administration has been looking for a universal carrier that can precisely transport traditional drugs, new genomic and proteic therapeutic agents. Today, researchers have found conditions to overcome the two main drug delivery dilemmas. On the one side, the versatility of the vehicle to efficiently load, protect and transport the drug and then release it at the target place. On the other hand, the questions related to the degree of PEGylation which are needed to avoid nanoparticle (NP) aggregation and opsonization while preventing cellular uptake. The development of different kinds of lipidic drug delivery vehicles and particles has resulted in the development of ionizable lipid nanoparticles (iLNPs), which can overcome most of the typical drug delivery problems. Proof of their success is the late approval and massive administration as the prophylactic vaccine for SARS-CoV-2. These ILNPs are built by electrostatic aggregation of surfactants, the therapeutic agent, and lipids that self-segregate from an aqueous solution, forming nanoparticles stabilized with lipid polymers, such as PEG. These vehicles overcome previous limitations such as low loading and high toxicity, likely thanks to low charge at the working pH and reduced size, and their entry into the cells via endocytosis rather than membrane perforation or fusion, always associated with higher toxicity. We herein revise their primary features, synthetic methods to prepare and characterize them, pharmacokinetic (administration, distribution, metabolization and excretion) aspects, and biodistribution and fate. Owing to their advantages, iLNPs are potential drug delivery systems to improve the management of various diseases and widely available for clinical use.
Prospects and challenges of environmental DNA (eDNA) metabarcoding in mangrove restoration in Southeast Asia
Authors: Wee Alison K. S. , Salmo III Severino G. , Sivakumar Kannan , Then Amy Y-H , Basyuni Mohammad , Fall Jean , Habib Kazi Ahsan , Isowa Yukinobu , Leopardas Venus , Peer Nasreen , Artigas-Ramirez Maria D. , Ranawana Kithsiri , Sivaipram Itchika , Suleiman Monica , Kajita Tadashi
Published: February 2023

Species detection using environmental DNA (eDNA) is a biomonitoring tool that can be widely applied to mangrove restoration and management. Compared to traditional surveys that are taxa-specific and time-consuming, eDNA metabarcoding offers a rapid, non-invasive and cost-efficient method for monitoring mangrove biodiversity and characterising the spatio-temporal distribution of multiple taxa simultaneously. General guidelines for eDNA metabarcoding are well-established for aquatic systems, but habitat-specific guidelines are still lacking. Mangrove habitats, as priority ecosystems for restoration in Southeast Asia, present unique prospects and challenges in these regards. Environmental DNA metabarcoding can be used to (1) track functional recovery in ecological restoration, (2) prioritise conservation areas, (3) provide early warning for threats, (4) monitor threatened taxa, (5) monitor response to climate change, and (6) support community-based restoration. However, these potential applications have yet been realized in Southeast Asia due to (1) technical challenges, (2) lack of standardised methods, (3) spatio-temporal difficulties in defining community, (4) data limitations, and (5) lack of funding, infrastructure and technical capacity. Successful implementation of eDNA metabarcoding in mangrove restoration activities would encourage the development of data-driven coastal management and equitable conservation programs. Eventually, this would promote Southeast Asia’s shared regional interests in food security, coastal defence and biodiversity conservation.
A study of volcanic rocks and ferromanganese crusts through marine geophysical methods integration in the north portion of Cruzeiro do Sul Rift in the Rio Grande Rise
Authors: Sergipe Paula Possamai , Louro Vinicius , Marangoni Yára Regina , de Moura Denise Silva , Jovane Luigi
Published: February 2023

The Rio Grande Rise (RGR) is an extensive structural high located in the South Atlantic Ocean, target of increasing exploratory interest. During the last decades, considerable attention has been given to its genesis, dynamic, regional tectonic, and composition. Some studies indicate the presence of volcanic rocks, mainly basaltic, related to their volcanic origin and Ferromanganese Crusts, boosting the research and economic interest. This study suggests the location of volcanic rocks and FeMn crusts at the north portion of Cruzeiro do Sul Rift within the RGR, characterizing the local geology and distribution pattern. We used multibeam bathymetry, sidescan sonar, dredges, and magnetic field data to integrate and better constrain the results. The magnetic field data highlighted the location of probable basaltic rocks, agreeing with the published literature, which was afterward confirmed by dredge samples. Their magnetic anomalies displayed the predominance of reverse polarization and less frequent normal polarization anomalies. FeMn crusts need a large volume of magnetite to cause anomalies in the local magnetic field, which does not happen in the RGR. There, they have reduced thickness and are frequently eroded, as displayed by the bathymetry, sidescan sonar, and geological data. Magnetic lineaments at the Rift margin defined a zone with a series of normal faults. During the Rift formation, transcurrent movements caused an intense fracturing, providing pathways for magma intrusion. Therefore, the fault zone could be related to the primary magnetic anomalies as a function of the magma intrusion and the occurrence of the rifting process and seafloor spreading. The new data presented in this paper brings valuable data for the comprehension and exploration effort of the RGR.
Estimating catch rates in real time: Development of a deep learning based Nephrops (Nephrops norvegicus) counter for demersal trawl fisheries
Authors: Avsar Ercan , Feekings Jordan P. , Krag Ludvig Ahm
Published: February 2023

Demersal trawling is largely a blind process where information on catch rates and compositions is only available once the catch is taken onboard the vessel. Obtaining quantitative information on catch rates of target species while fishing can improve a fisheries economic and environmental performance as fishers would be able to use this information to make informed decisions during fishing. Despite there are real-time underwater monitoring systems developed for this purpose, the video data produced by these systems is not analyzed in near real-time. In other words, the user is expected to watch the video feed continuously to evaluate catch rates and composition. This is obviously a demanding process in which quantification of the fish counts will be of a qualitative nature. In this study, underwater footages collected using an in-trawl video recording system were processed to detect, track, and count the number of individuals of the target species, Nephrops norvegicus, entering the trawl in real-time. The detection was accomplished using a You Only Look Once v4 (YOLOv4) algorithm. Two other variants of the YOLOv4 algorithm (tiny and scaled) were included in the study to compare their effects on the accuracy of the subsequent steps and overall speed of the processing. SORT algorithm was used as the tracker and any Nephrops that cross the horizontal level at 4/5 of the frame height were counted as catch. The detection performance of the YOLOv4 model provided a mean average precision (mAP@50) value of 97.82%, which is higher than the other two variants. However, the average processing speed of the tiny model is the highest with 253.51 frames per second. A correct count rate of 80.73% was achieved by YOLOv4 when the total number of Nephrops are considered in all the test videos. In conclusion, this approach was successful in processing underwater images in real time to determine the catch rates of the target species. The approach has great potential to process multiple species simultaneously in order to provide quantitative information not only on the target species but also bycatch and unwanted species to provide a comprehensive picture of the catch composition.
Dexmedetomidine only regimen for long-term sedation is associated with reduced vasopressor requirements in septic shock patients: A retrospective cohort study from MIMIC-IV database
Authors: Li Lulan , Shi Xiaotong , Xiong Ming , Kong Karen , Chen Zhongqing , Zhou Shiyu , Zeng Zhenhua , An Shengli , Xu Bo
Published: February 2023

Background

Previous studies have shown that dexmedetomidine (DEX) may be associated with reduced vasopressor requirements in septic shock patients, however, long-term DEX-only sedation in reducing vasopressor requirements is still controversial.

Methods

A retrospective study was conducted among patients with septic shock on mechanical ventilation using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcome was the ratio of norepinephrine equivalent dose to mean arterial pressure (NEq/MAP) in the first 72 h after DEX or other sedatives for sedation. The secondary outcomes were key organ function parameters, 28-day mortality, and 90-day mortality. Univariate, propensity score matching (PSM), and generalized linear mixed model (GLMM) analyses were performed.

Results

DEX was associated with decreased NEq/MAP in the first 72 h (difference = 0.05, 95% CI = –0.02–0.08, p = 0.002) after adjusting for confounders in the GLMM analysis. The DEX group was also associated with a lower heart rate, cardiac output (CO), lactate level, aspartate transaminase (AST) level, and higher PaO2/FiO2 ratio (p < 0.0125). Moreover, DEX only sedation was associated with reduced 90-day mortality (OR = 0.60, 95% CI = 0.37–0.94, p = 0.030).

Conclusion

DEX may be associated with decreased vasopressor requirements, improved AST and PaO2/FiO2 levels, and reduced 90-day mortality in patients with septic shock, which warrants further study.