bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel ultrasound techniques in the identification of vulnerable plaques—an updated review of the literature
Authors: Yao Yujuan , Zhang Pingyang
Published: May 2023

Atherosclerosis is an inflammatory disease partly mediated by lipoproteins. The rupture of vulnerable atherosclerotic plaques and thrombosis are major contributors to the development of acute cardiovascular events. Despite various advances in the treatment of atherosclerosis, there has been no satisfaction in the prevention and assessment of atherosclerotic vascular disease. The identification and classification of vulnerable plaques at an early stage as well as research of new treatments remain a challenge and the ultimate goal in the management of atherosclerosis and cardiovascular disease. The specific morphological features of vulnerable plaques, including intraplaque hemorrhage, large lipid necrotic cores, thin fibrous caps, inflammation, and neovascularisation, make it possible to identify and characterize plaques with a variety of invasive and non-invasive imaging techniques. Notably, the development of novel ultrasound techniques has introduced the traditional assessment of plaque echogenicity and luminal stenosis to a deeper assessment of plaque composition and the molecular field. This review will discuss the advantages and limitations of five currently available ultrasound imaging modalities for assessing plaque vulnerability, based on the biological characteristics of the vulnerable plaque, and their value in terms of clinical diagnosis, prognosis, and treatment efficacy assessment.
Impact of polyphenols on heart failure and cardiac hypertrophy: clinical effects and molecular mechanisms
Authors: Hedayati Neda , Yaghoobi Alireza , Salami Marziyeh , Gholinezhad Yasaman , Aghadavood Farnaz , Eshraghi Reza , Aarabi Mohammad-Hossein , Homayoonfal Mina , Asemi Zatollah , Mirzaei Hamed , Hajijafari Mohammad , Mafi Alireza , Rezaee Malihe
Published: May 2023

Polyphenols are abundant in regular diets and possess antioxidant, anti-inflammatory, anti-cancer, neuroprotective, and cardioprotective effects. Regarding the inadequacy of the current treatments in preventing cardiac remodeling following cardiovascular diseases, attention has been focused on improving cardiac function with potential alternatives such as polyphenols. The following online databases were searched for relevant orginial published from 2000 to 2023: EMBASE, MEDLINE, and Web of Science databases. The search strategy aimed to assess the effects of polyphenols on heart failure and keywords were “heart failure” and “polyphenols” and “cardiac hypertrophy” and “molecular mechanisms”. Our results indicated polyphenols are repeatedly indicated to regulate various heart failure-related vital molecules and signaling pathways, such as inactivating fibrotic and hypertrophic factors, preventing mitochondrial dysfunction and free radical production, the underlying causes of apoptosis, and also improving lipid profile and cellular metabolism. In the current study, we aimed to review the most recent literature and investigations on the underlying mechanism of actions of different polyphenols subclasses in cardiac hypertrophy and heart failure to provide deep insight into novel mechanistic treatments and direct future studies in this context. Moreover, due to polyphenols' low bioavailability from conventional oral and intravenous administration routes, in this study, we have also investigated the currently accessible nano-drug delivery methods to optimize the treatment outcomes by providing sufficient drug delivery, targeted therapy, and less off-target effects, as desired by precision medicine standards.
Genetic landscape in Russian patients with familial left ventricular noncompaction
Authors: Meshkov Alexey N. , Myasnikov Roman P. , Kiseleva Anna V. , Kulikova Olga V. , Sotnikova Evgeniia A. , Kudryavtseva Maria M. , Zharikova Anastasia A. , Koretskiy Sergey N. , Mershina Elena A. , Ramensky Vasily E. , Zaicenoka Marija , Vyatkin Yuri V. , Kharlap Maria S. , Nikityuk Tatiana G. , Sinitsyn Valentin E. , Divashuk Mikhail G. , Kutsenko Vladimir A. , Basargina Elena N. , Barskiy Vladimir I. , Sdvigova Nataliya A. , Skirko Olga P. , Efimova Irina A. , Pokrovskaya Maria S. , Drapkina Oxana M.
Published: May 2023

Background

Left ventricular noncompaction (LVNC) cardiomyopathy is a disorder that can be complicated by heart failure, arrhythmias, thromboembolism, and sudden cardiac death. The aim of this study is to clarify the genetic landscape of LVNC in a large cohort of well-phenotyped Russian patients with LVNC, including 48 families (n=214).

Methods

All index patients underwent clinical examination and genetic analysis, as well as family members who agreed to participate in the clinical study and/or in the genetic testing. The genetic testing included next generation sequencing and genetic classification according to ACMG guidelines.

Results

A total of 55 alleles of 54 pathogenic and likely pathogenic variants in 24 genes were identified, with the largest number in the MYH7 and TTN genes. A significant proportion of variants −8 of 54 (14.8%) −have not been described earlier in other populations and may be specific to LVNC patients in Russia. In LVNC patients, the presence of each subsequent variant is associated with increased odds of having more severe LVNC subtypes than isolated LVNC with preserved ejection fraction. The corresponding odds ratio is 2.77 (1.37 −7.37; p <0.001) per variant after adjustment for sex, age, and family.

Conclusion

Overall, the genetic analysis of LVNC patients, accompanied by cardiomyopathy-related family history analysis, resulted in a high diagnostic yield of 89.6%. These results suggest that genetic screening should be applied to the diagnosis and prognosis of LVNC patients.
Reading comprehension performance of elementary and senior high school students
Authors: de Oliveira Adriana Marques , Santos Jair Lício Ferreira , Capellini Simone Aparecida
Published: May 2023

Introduction

In Brazil, reading has been widely discussed, mainly due to the published results of national and international performance exams of Brazilian schoolchildren. Learning to read is therefore a continuous process, and the ability to make inferences while reading a text develops with age. The textual complexity involving the syntactic structuring, vocabulary and types of text progressively increases from the initial years of elementary school to high school students, also increasing the cognitive demand of the students; this occurs in parallel to their development and school advancement, which allows improvements in their teaching/learning processes. Based on the above, the following questions were raised: (1) How is the semantic process of reading established among elementary school students in elementary school (cycle II) and high school? Aim: to characterize the performance of elementary and senior high school students on semantic process tests from the Brazilian adaptation of the evaluation of reading processes (PROLEC-SE-R).

Methods

A total of 436 students of both sexes, aged between 11 and 18 years, participated. They were evaluated with Assessment of Reading Processes-PROLEC-SE-R.

Results and discussion

The results indicated that the semantic process was equally established among high school students, with a higher average performance compared with that of elementary school students. Among elementary school students, there was progression in the average correct answers with advancement in schooling. In the two levels of education, narrative texts allowed a greater number of correct answers, followed by multiple-choice and literal questions. The PROLEC-SE-R semantic process tests proved to be effective for assessing reading comprehension in elementary and high school students and reflected the Brazilian reality with regard to the gaps and weaknesses in the educational system.
Association between pediatric asthma and adult polycystic ovarian syndrome (PCOS): a cross-sectional analysis of the UAE healthy future Study (UAEHFS)
Authors: Juber Nirmin F. , Abdulle Abdishakur , AlJunaibi Abdulla , AlNaeemi Abdulla , Ahmad Amar , Leinberger-Jabari Andrea , Al Dhaheri Ayesha S. , AlZaabi Eiman , Mezhal Fatima , Al-Maskari Fatma , Alanouti Fatme , Alsafar Habiba , Alkaabi Juma , Wareth Laila Abdel , Aljaber Mai , Kazim Marina , Weitzman Michael , Al-Houqani Mohammed , Hag-Ali Mohammed , Oumeziane Naima , El-Shahawy Omar , Sherman Scott , Shah Syed M. , Loney Tom , Almahmeed Wael , Idaghdour Youssef , Ali Raghib
Published: May 2023

Introduction

Asthma and polycystic ovarian syndrome (PCOS) are linked in several possible ways. To date, there has been no study evaluating whether pediatric asthma is an independent risk factor for adult PCOS. Our study aimed to examine the association between pediatric asthma (diagnosed at 0-19 years) and adult PCOS (diagnosed at ≥20 years). We further assessed whether the aforementioned association differed in two phenotypes of adult PCOS which were diagnosed at 20-25 years (young adult PCOS), and at >25 years (older adult PCOS). We also evaluated whether the age of asthma diagnosis (0-10 vs 11-19 years) modified the association between pediatric asthma and adult PCOS.

Material and methods

This is a retrospective cross-sectional analysis using the United Arab Emirates Healthy Future Study (UAEHFS) collected from February 2016 to April 2022 involving 1334 Emirati females aged 18-49 years. We fitted a Poisson regression model to estimate the risk ratio (RR) and its 95% confidence interval (95% CI) to assess the association between pediatric asthma and adult PCOS adjusting for age, urbanicity at birth, and parental smoking at birth.

Results

After adjusting for confounding factors and comparing to non-asthmatic counterparts, we found that females with pediatric asthma had a statistically significant association with adult PCOS diagnosed at ≥20 years (RR=1.56, 95% CI: 1.02-2.41), with a stronger magnitude of the association found in the older adult PCOS phenotype diagnosed at >25 years (RR=2.06, 95% CI: 1.16-3.65). Further, we also found females reported thinner childhood body size had a two-fold to three-fold increased risk of adult PCOS diagnosed at ≥20 years in main analysis and stratified analyses by age of asthma and PCOS diagnoses (RR=2.06, 95% CI: 1.08-3.93 in main analysis; RR=2.74, 95% CI: 1.22-6.15 among those diagnosed with PCOS > 25 years; and RR=3.50, 95% CI: 1.38-8.43 among those diagnosed with asthma at 11-19 years).

Conclusions

Pediatric asthma was found to be an independent risk factor for adult PCOS. More targeted surveillance for those at risk of adult PCOS among pediatric asthmatics may prevent or delay PCOS in this at-risk group. Future studies with robust longitudinal designs aimed to elucidate the exact mechanism between pediatric asthma and PCOS are warranted.
Identification of zona pellucida defects revealed a novel loss-of-function mutation in ZP2 in humans and rats
Authors: Zeng Jun , Sun Ying , Zhang Jing , Wu Xiaozhu , Wang Yan , Quan Ruping , Song Wanjuan , Guo Dan , Wang Shengran , Chen Jianlin , Xiao Hongmei , Huang Hua-Lin
Published: May 2023

Introduction

Human zona pellucida (ZP) plays an important role in reproductive process. Several rare mutations in the encoding genes (ZP1, ZP2, and ZP3) have been demonstrated to cause women infertility. Mutations in ZP2 have been reported to cause ZP defects or empty follicle syndrome. We aimed to identify pathogenic variants in an infertile woman with a thin zona pellucida (ZP) phenotype and investigated the effect of ZP defects on oocyte gene transcription.

Methods

We performed whole-exome sequencing and Sanger sequencing of genes were performed for infertilite patients characterized by fertilization failure in routine in vitro fertilization (IVF). Immunofluorescence (IF) and intracytoplasmic sperm injection (ICSI) were used in the mutant oocytes. Single-cell RNA sequencing was used to investigate transcriptomes of the gene-edited (Zp2mut/mut) rat model. Biological function enrichment analysis, quantitative real-time PCR (qRT-PCR), and IF were performed.

Results

We identified a novel homozygous nonsense mutation of ZP2 (c.1924C > T, p.Arg642X) in a patient with non-consanguineous married parents. All oocytes showed a thin or no ZP under a light microscope and were fertilized after ICSI. The patient successfully conceived by receiving the only two embryos that developed to the blastocyst stage. The immunofluorescence staining showed an apparently abnormal form of the stopped oocytes. We further demonstrated a total of 374 differentially expressed genes (DEGs) in the transcriptome profiles of Zp2mut/mut rats oocytes and highlighted the signal communication between oocytes and granulosa cells. The pathway enrichment results of DEGs showed that they were enriched in multiple signaling pathways, especially the transforming growth factor-β (TGF-β) signaling pathway in oocyte development. qRT-PCR, IF, and phosphorylation analysis showed significantly downregulated expressions of Acvr2b, Smad2, p38MAPK, and Bcl2 and increased cleaved-caspase 3 protein expression.

Discussion

Our findings expanded the known mutational spectrum of ZP2 associated with thin ZP and natural fertilization failure. Disruption of the integrity of the ZP impaired the TGF-β signaling pathway between oocytes and surrounding granulosa cells, leading to increased apoptosis and decreased developmental potential of oocytes.
The emerging role of circadian rhythms in the development and function of thermogenic fat
Authors: Peng Xuemin , Chen Yong
Published: May 2023

Circadian rhythms regulate many biological processes in response to ambient influences. A disrupted circadian rhythm has been shown to be associated with obesity and obesity-related metabolic disorders. Thermogenic fat, including brown and beige fat, may play an important role in this process since it displays a high capacity to burn fat and release the stored energy as heat, contributing to the combat against obesity and its associated metabolic disorders. In this review, we summarize the relationship between the circadian clock and thermogenic fat and the prominent mechanisms which are involved in the regulation of the development and function of thermogenic fat by circadian rhythms, which may provide novel therapeutics for the prevention and treatment of metabolic diseases by targeting thermogenic fat in a circadian manner.
Detecting and measuring of GPCR signaling – comparison of human induced pluripotent stem cells and immortal cell lines
Authors: Chen Gaoxian , Obal Detlef
Published: May 2023

G protein-coupled receptors (GPCRs) are a large family of transmembrane proteins that play a major role in many physiological processes, and thus GPCR-targeted drug development has been widely promoted. Although research findings generated in immortal cell lines have contributed to the advancement of the GPCR field, the homogenous genetic backgrounds, and the overexpression of GPCRs in these cell lines make it difficult to correlate the results with clinical patients. Human induced pluripotent stem cells (hiPSCs) have the potential to overcome these limitations, because they contain patient specific genetic information and can differentiate into numerous cell types. To detect GPCRs in hiPSCs, highly selective labeling and sensitive imaging techniques are required. This review summarizes existing resonance energy transfer and protein complementation assay technologies, as well as existing and new labeling methods. The difficulties of extending existing detection methods to hiPSCs are discussed, as well as the potential of hiPSCs to expand GPCR research towards personalized medicine.
Trends and variability in methane concentrations over the Southeastern Arabian Peninsula
Authors: Francis Diana , Weston Michael , Fonseca Ricardo , Temimi Marouane , Alsuwaidi Aisha
Published: May 2023

Methane (CH4) is a potent greenhouse gas with an important contribution to global warming. While national and international efforts have been put in place to reduce methane emissions, little is known about its variability, especially in hotspot regions where natural and anthropogenic emissions are compounded. In this study, the current state of CH4 concentrations and their trends over the United Arab Emirates (UAE) and surrounding region are investigated with satellite and reanalysis data. CH4 concentrations have increased over the last 5 years, with a trend in the satellite-derived column values (XCH4) of about 9 ppb/year. A clear annual cycle is detected in XCH4, with an amplitude of up to 75 ppb and peak values in the warmer months. The largest concentrations are found in coastal sites, where sabkhas and landfills are present, and along the Al Hajar mountains, where agricultural activities and microhabitats that may host CH4-producing microbes occur and where advection by the background flow is likely an important contributor. The reanalysis data shows a good agreement with the satellite-derived estimates in terms of the spatial pattern, but the magnitudes are smaller by up to 50 ppb, due to deficiencies in the data assimilated. Surface CH4 concentrations in the reanalysis data account for more than 50% of the corresponding XCH4 values, and exhibit a seasonal cycle with the opposite phase due to uncertainties in the emissions inventory. Our findings provide an overview of the state of CH4 concentration in the UAE and surrounding region, and may aid local authorities to propose the appropriate emission reduction strategies in order to meet the proposed net-zero greenhouse gas emission target by 2050. This study highlights the need for the establishment in the Arabian Peninsula region of a ground-based observational network for greenhouse gas concentrations which is still lacking to date.
A unifying framework for understanding ecological and evolutionary population connectivity
Authors: Cramer Alli N. , Hoey Jennifer A. , Dolan Tara E. , Gatins Remy , Toy Jason A. , Chancellor Jordan L. , Palkovacs Eric P. , Garza John Carlos , Beltran Roxanne S.
Published: May 2023

Although the concept of connectivity is ubiquitous in ecology and evolution, its definition is often inconsistent, particularly in interdisciplinary research. In an ecological context, population connectivity refers to the movement of individuals or species across a landscape. It is measured by locating organisms and tracking their occurrence across space and time. In an evolutionary context, connectivity is typically used to describe levels of current and past gene flow, calculated from the degree of genetic similarity between populations. Both connectivity definitions are useful in their specific contexts, but rarely are these two perspectives combined. Different definitions of connectivity could result in misunderstandings across subdisciplines. Here, we unite ecological and evolutionary perspectives into a single unifying framework by advocating for connectivity to be conceptualized as a generational continuum. Within this framework, connectivity can be subdivided into three timescales: (1) within a generation (e.g., movement), (2) across one parent-offspring generation (e.g., dispersal), and (3) across two or more generations (e.g., gene flow), with each timescale determining the relevant context and dictating whether the connectivity has ecological or evolutionary consequences. Applying our framework to real-world connectivity questions can help to identify sampling limitations associated with a particular methodology, further develop research questions and hypotheses, and investigate eco-evolutionary feedback interactions that span the connectivity continuum. We hope this framework will serve as a foundation for conducting and communicating research across subdisciplines, resulting in a more holistic understanding of connectivity in natural systems.
The response of Tampa Bay to a legacy mining nutrient release in the year following the event
Authors: Morrison Elise S. , Phlips Edward , Badylak Susan , Chappel Amanda R. , Altieri Andrew H. , Osborne Todd Z. , Tomasko David , Beck Marcus W. , Sherwood Edward
Published: May 2023

Introduction

Cultural eutrophication threatens numerous ecological and economical resources of Florida’s coastal ecosystems, such as beaches, mangroves, and seagrasses. In April 2021, an infrastructure failure at the retired Piney Point phosphorus mining retention reservoir garnered national attention, as 814 million liters of nutrient rich water were released into Tampa Bay, Florida over 10 days. The release of nitrogen and phosphorus-rich water into Tampa Bay – a region that had been known as a restoration success story since the 1990s – has highlighted the potential for unexpected challenges for coastal nutrient management.

Methods

For a year after the release, we sampled bi-weekly at four sites to monitor changes in nutrients, stable isotopes, and phytoplankton communities, complemented with continuous monitoring by multiparameter sondes. Our data complement the synthesis efforts of regional partners, the Tampa Bay and Sarasota Bay Estuary Programs, to better understand the effects of anthropogenic nutrients on estuarine health.

Results

Phytoplankton community structure indicated an initial diatom bloom that dissipated by the end of April 2021. In the summer, the bay was dominated by Karenia brevis, with conditions improving into the fall. To determine if there was a unique carbon (C) and nitrogen (N) signature of the discharge water, stable isotope values of carbon (δ13C) and nitrogen (δ15N) were analyzed in suspended particulate material (SPM). The δ15N values of the discharge SPM were −17.88‰ ± 0.76, which is exceptionally low and was unique relative to other nutrient sources in the region. In May and early June of 2021, all sites exhibited a decline in the δ15N values of SPM, suggesting that discharged N was incorporated into SPM after the event. The occurrence of very low δ15N values at the reference site, on the Gulf Coast outside of the Bay, indicates that some of the discharge was transported outside of Tampa Bay.

Discussion

This work illustrates the need for comprehensive nutrient management strategies to assess and manage the full range of consequences associated with anthropogenic nutrient inputs into coastal ecosystems. Ongoing and anticipated impacts of climate change – such as increasing tropical storm intensity, temperatures, rainfall, and sea level rise – will exacerbate this need.
Urban sprawl at the expense of cultivated land: decadal land use and land cover changes and future projections in the upper Awash basin of central Ethiopia
Authors: Hirpa Birtukan Abebe , Adane Girma Berhe , Asrat Asfawossen , Nedaw Dessie , Song Cholho , Roh Minwoo , Lee Woo-Kyun
Published: May 2023

Introduction

Urban sprawl in developing countries affects future sustainability concerns related to environment, ecology and cropland losses. This study aimed at identifying, classifying and quantifying the changes in land-use and land-cover (LULC) during the last two decades (2000–2020) and predict the decadal pattern for the next three decades (2030–2050), with particular emphasis on urban sprawl at the expense of cultivated land in the upper Awash basin of central Ethiopia.

Methods

Landsat images were used to analyze the LULC change dynamics using hybrid image classification and maximum likelihood classifier techniques. The Cellular Automata-Markov Chain (CAMC) Model was used to predict its future LULC change dynamics. A detailed analysis of the urban sprawl in the cities of Addis Ababa, Adama, and Mojo was also conducted.

Results

It was observed that during the last two decades, settlements, particularly urban sprawls, substantially expanded at the expense of cultivated land, whereas the latter modestly expanded at the expense of forestland, bare land, and shrubland. From its size in 2000, the urban sprawl of Addis Ababa has grown in all directions towards cultivated land by more than six times in 2020 and is expected to become double of that by 2050 in the urban and peri-urban areas of the basin. Adama city has expanded by the same rate of 9.7% in the past two decades, while Mojo town has sprawled 9 folds between 2010 and 2020. The predicted percentage change in settlement for Addis Ababa and its neighboring districts within 22 km radius from the centroid shows a 40% expansion in 2030, 77% in 2040, and 87% in 2050 compared with the reference year 2020. Similarly, the Mojo town will expand significantly in 2030 (54%), 2040 (119%), and 2050 (by a staggering magnitude of 244%), while Adama will expand within the 12 km radius by 18%, 42%, and 117% in the next three respective decades.

Discussion

The rapid cultivated land conversions in the basin may contribute to major shifts in urban and peri-urban ecological environments. Our predictive LULC change maps and urban sprawling could be useful for developing effective and sustainable land-use policies for environmental and ecological management in the upper Awash basin.
LCAT: an isoform-sensitive error correction for transcriptome sequencing long reads
Authors: Zhu Wufei , Liao Xingyu
Published: May 2023

As the carrier of genetic information, RNA carries the information from genes to proteins. Transcriptome sequencing technology is an important way to obtain transcriptome sequences, and it is also the basis for transcriptome research. With the development of third-generation sequencing, long reads can cover full-length transcripts and reflect the composition of different isoforms. However, the high error rate of third-generation sequencing affects the accuracy of long reads and downstream analysis. The current error correction methods seldom consider the existence of different isoforms in RNA, which makes the diversity of isoforms a serious loss. Here, we introduce LCAT (long-read error correction algorithm for transcriptome sequencing data), a wrapper algorithm of MECAT, to reduce the loss of isoform diversity while keeping MECAT’s error correction performance. The experimental results show that LCAT can not only improve the quality of transcriptome sequencing long reads but also retain the diversity of isoforms.
Disturbed microbiota-metabolites-immune interaction network is associated with olfactory dysfunction in patients with chronic rhinosinusitis
Authors: Han Xingyu , He Xuejia , Zhan Xiaojun , Yao Linyin , Sun Zhifu , Gao Xing , Wang Shan , Wang Zhenlin
Published: May 2023

Purpose

Olfactory dysfunction (OD) is a debilitating symptom frequently reported by patients with chronic rhinosinusitis (CRS) and it is associated with a dysregulated sinonasal inflammation. However, little information is available about the effect of the inflammation-related nasal microbiota and related metabolites on the olfactory function in these patients. Therefore, the current study aimed to investigate the nasal microbiota-metabolites-immune interactions and their role in the pathogenesis of OD in CRS patients.

Methods

23 and 19 CRS patients with and without OD, respectively, were enrolled in the present study. The “Sniffin’ Sticks” was used to measure the olfactory function, while the metagenomic shotgun sequencing and the untargeted metabolite profiling were performed to assess the differences in terms of the nasal microbiome and metabolome between the two groups. The levels of nasal mucus inflammatory mediators were investigated by a multiplex flow Cytometric Bead Array (CBA).

Results

A decreased diversity in the nasal microbiome from the OD group compared to the NOD group was evidenced. The metagenomic analysis revealed a significant enrichment of Acinetobacter johnsonii in the OD group, while Mycoplasma arginini, Aeromonas dhakensis, and Salmonella enterica were significantly less represented (LDA value > 3, p < 0.05). The nasal metabolome profiles were significantly different between the OD and NOD groups (P < 0.05). The purine metabolism was the most significantly enriched metabolic subpathway in OD patients compared with NOD patients (P < 0.001). The expressions of IL-5, IL-8, MIP-1α, MCP-1, and TNF were statistically and significantly increased in the OD group (P < 0.05). All these data, including the dysregulation of the nasal microbiota, differential metabolites, and elevated inflammatory mediators in OD patients demonstrated a clear interaction relationship.

Conclusion

The disturbed nasal microbiota-metabolite-immune interaction networks may be implicated in the pathogenesis of OD in CRS patients and the underlying pathophysiological mechanisms need to be further investigated in future studies.
Abrine, an IDO1 inhibitor, suppresses the immune escape and enhances the immunotherapy of anti-PD-1 antibody in hepatocellular carcinoma
Authors: Liang Xiaowei , Gao Hongwei , Xiao Jian , Han Shan , He Jia , Yuan Renyikun , Yang Shilin , Yao Chun
Published: May 2023

Background

Indoleamine-2,3-dioxygenase 1 (IDO1) is responsible for tumor immune escape by regulating T cell-associated immune responses and promoting the activation of immunosuppressive. Given the vital role of IDO1 in immune response, further investigation on the regulation of IDO1 in tumors is needed.

Methods

Herein, we used ELISA kit to detect the interferon-gamma (IFN-γ), Tryptophan (Trp), and kynurenic acid (Kyn) levels; western blot, Flow cytometry, and immunofluorescence assays detected the expression of the proteins; Molecular docking assay, SPR assay and Cellular Thermal Shift Assay (CETSA) were used to detect the interaction between IDO1 and Abrine; nano live label-free system was used to detect the phagocytosis activity; tumor xenografts animal experiments were used to explore the anti-tumor effect of Abrine; flow cytometry detected the immune cells changes.

Results

The important immune and inflammatory response cytokine interferon-gamma (IFN-γ) up-regulated the IDO1 expression in cancer cells through the methylation of 6-methyladenosine (m6A) m6A modification of RNA, metabolism of Trp into Kyn, and JAK1/STAT1 signaling pathway, which could be inhibited by IDO1 inhibitor Abrine. CD47 is IFN-γ-stimulated genes (ISGs) and prevents the phagocytosis of macrophages, leading to the cancer immune escape, and this effect could be inhibited by Abrine both in vivo and in vitro. The PD-1/PD-L1 axis is an important immune checkpoint in regulating immune response, overexpression of PD-1 or PD-L1 promotes immune suppression, while in this study Abrine could inhibit the expression of PD-L1 in cancer cells or tumor tissue. The combination treatment of Abrine and anti-PD-1 antibody has a synergistic effect on suppressing the tumor growth through up-regulating CD4+ or CD8+ T cells, down-regulating the Foxp3+ Treg cells, and inhibiting the expression of IDO1, CD47, and PD-L1.

Conclusion

Overall, this study reveals that Abrine as an IDO1 inhibitor has an inhibition effect on immune escape and has a synergistic effect with the anti-PD-1 antibody on the treatment of HCC.
“Trained Immunity” from Mycobacterium spp. exposure (BCG vaccination and environmental) may have an impact on the incidence of early childhood leukemia
Authors: Singh Samer , Kishore Dhiraj , Singh Rakesh K.
Published: May 2023

Preventive variables for childhood leukemia incidence (LI) remain unknown. Past assertions that childhood vaccinations, especially BCG, may be potentially protective have remained disputed for over five decades because of the lack of a unifying framework to explain variable outcomes in different studies. An examination of the early childhood LI for 2020 in European Region countries with supposedly similar underlying confounders but differential childhood vaccination coverage displays negative covariation with prevailing Mycobacterium spp. exposure in BCG-vaccinated children. The childhood LI in 0–4-year-old populations with >90% childhood BCG vaccination coverage is found to be strongly but negatively correlated with prevailing tuberculin immunoreactivity [r(24): -0.7868, p-value: < 0.0001]. No such correlation existed for the LI in 0–4-year-old populations without BCG vaccinations, though weak associations are hinted at by the available data for MCV2, PCV3, and DTP3 vaccinations. We hypothesize that early childhood BCG vaccination “priming” and subsequent “trained immunity” augmentation by “natural” boosting from Mycobacterium spp. exposure play a preventive and protective role in childhood LI. The non-consideration of prevailing “trained immunity” could have been a cause behind the conflicting outcomes in past studies. Exploratory studies, preferably performed in high-burden countries and controlling for the trained-immunity correlate and other potential confounders, would be warranted in order to establish a role for BCG vaccination and early-life immune training (or lack thereof) in childhood LI and help put the current controversy to rest.
Ovalbumin-specific CD4+ and CD8+ T cells contribute to different susceptibility for Theiler’s murine encephalomyelitis virus persistence
Authors: Wannemacher Rouven , Reiß Anna , Rohn Karl , Lühder Fred , Flügel Alexander , Baumgärtner Wolfgang , Hülskötter Kirsten
Published: May 2023

Theiler’s murine encephalomyelitis virus (TMEV) is the causative agent of TMEV-induced demyelinating disease (TMEV-IDD); a well-established animal model for the chronic progressive form of human multiple sclerosis (MS). In susceptible mice with an inadequate immune response, TMEV-IDD is triggered by virus persistence and maintained by a T cell mediated immunopathology. OT-mice are bred on a TMEV-resistant C57BL/6 background and own predominantly chicken ovalbumin (OVA)-specific populations of CD8+ T cells (OT-I) or CD4+ T cells (OT-II), respectively. It is hypothesized that the lack of antigen specific T cell populations increases susceptibility for a TMEV-infection in OT-mice on a TMEV-resistant C57BL/6 background. OT-I, OT-II, and C57BL/6 control mice were infected intracerebrally with the TMEV-BeAn strain. Mice were scored weekly for clinical disease and after necropsy, histological and immunohistochemical evaluation was performed. OT-I mice started to develop progressive motor dysfunction between 7 and 21 days post infection (dpi), leading up to hind limb paresis and critical weight loss, which resulted in euthanasia for humane reasons between 14 and 35 dpi. OT-I mice displayed a high cerebral virus load, an almost complete absence of CD8+ T cells from the central nervous system (CNS) and a significantly diminished CD4+ T cell response. Contrarily, only 60% (12 of 20) of infected OT-II mice developed clinical disease characterized by mild ataxia. 25% of clinically affected OT-II mice (3 of 12) made a full recovery. 5 of 12 OT-II mice with clinical disease developed severe motor dysfunction similar to OT-I mice and were euthanized for humane reasons between 13 and 37 dpi. OT-II mice displayed only low virus-immunoreactivity, but clinical disease correlated well with severely reduced infiltration of CD8+ T cells and the increased presence of CD4+ T cells in the brains of OT-II mice. Though further studies are needed to reveal the underlying pathomechanisms following TMEV infection in OT mice, findings indicate an immunopathological process as a main contributor to clinical disease in OT-II mice, while a direct virus-associated pathology may be the main contributor to clinical disease in TMEV-infected OT-I mice.
The use of influential power in ocean governance
Authors: Haas Bianca , Jaeckel Aline , Pouponneau Angelique , Sacedon Randa , Singh Gerald G. , Cisneros-Montemayor Andrés M.
Published: May 2023

Ensuring inclusivity, especially the meaningful participation of diverse actors, is a key component of good governance. However, existing ocean governance frameworks have not yet achieved an equitable and fair playing field and are indeed often characterized by inequitable practices. In this perspective piece, we argue that one of the reasons for this lack of inclusion are the existing power frameworks and ways in which power is exercised within fora nominally intended to foster inclusion and cooperation. By focusing on four case studies of basic ocean governance processes, we explore how influential and interactive power is exercised in intergovernmental meetings, international conferences, and regional negotiations. These case studies demonstrate how specific exercises of power that undermine procedural inclusivity influence decision-making and the setting of agendas, and exclude important voices from ocean governance fora. This perspective piece contributes to the existing literature on power by highlighting how power is exercised within fundamental aspects of ocean governance. This paper merely scratches the surface, and more actions and research are needed to uncover and, more importantly, reverse deeply-rooted and self-perpetuating power structures in ocean governance.
A molluscan class struggle: exploring the surprisingly uneven distribution of chemosymbiosis among two major mollusk groups
Authors: Hughes Ian V. , Girguis Peter R.
Published: May 2023

Many bivalves and gastropods from marine reducing environments such as deep ocean hydrothermal vents and seeps host chemosynthetic bacteria in a nutritional symbiosis. Despite their functional similarities, the distribution of chemosymbiosis in these two mollusk classes is surprisingly uneven: the number of bivalve species known to host chemosynthetic symbionts is more than twenty times that of gastropods, and chemosymbiotic bivalves are reported from a far greater diversity of marine habitats. Here we explore the potential drivers for this trend, including but not limited to physiological differences, habitat characteristics, and sampling bias. Sampling bias likely contributes to the magnitude of the observed discrepancy, but we posit that the phenomenon itself reveals how intrinsic (e.g. morphology) and extrinsic (e.g. organic matter availability) factors might have shaped the distribution of extant gastropod and bivalve associations. These observations also serve as an impetus for increasing investigation into gastropods and other mollusks from chemically reducing environments to better understand the evolution and ecology of chemosymbiosis among molluscan hosts.
Anthropogenic nitrogen pollution threats and challenges to the health of South Asian coral reefs
Authors: Painter Stuart C. , Artioli Yuri , Amir Fathimath Hana , Arnull Jessica , Ganeshram Raja S. , Ibrahim Nizam , Samuel V. Deepak , Robin R.S. , Raghuraman R. , Purvaja R. , Ramesh R. , Rajasuriya Arjan , Rendon Olivia R. , Shazly Aminath , Wilson A. Meriwether W. , Tudhope Alexander W.
Published: May 2023

Nitrogen pollution is a widespread and growing problem in the coastal waters of South Asia yet the ecological impacts on the region’s coral ecosystems are currently poorly known and understood. South Asia hosts just under 7% of global coral reef coverage but has experienced significant and widespread coral loss in recent decades. The extent to which this coral ecosystem decline at the regional scale can be attributed to the multiple threats posed by nitrogen pollution has been largely overlooked in the literature. Here, we assess the evidence for nitrogen pollution impacts on corals in the central Indian Ocean waters of India, Sri Lanka and the Maldives. We find that there is currently limited evidence with which to clearly demonstrate widespread impacts on coral reefs from nitrogen pollution, including from its interactions with other stressors such as seawater warming. However, this does not prove there are no significant impacts, but rather it reflects the paucity of appropriate observations and related understanding of the range of potential impacts of nitrogen pollution at individual, species and ecosystem levels. This situation presents significant research, management and conservation challenges given the wide acceptance that such pollution is problematic. Following from this, we recommend more systematic collection and sharing of robust observations, modelling and experimentation to provide the baseline on which to base prescient pollution control action.
A historical overview of water quality in the coastal seas of China
Authors: Xin Ming , Sun Xia , Xie Lin-Ping , Wang Bao-Dong
Published: May 2023

Using historical data, long-term variations in pollutant sources and water quality in China’s coastal waters over the last three decades are reviewed. The results show that the total area of non-clean water, which reflects state of total water quality, increased rapidly before 2000, but then underwent two stages of decline, with a modest decline by one-quarter between 2001 and 2015, followed by a sharp decline of more than half of that in 2015 since then. Consequently, water quality at present is better than it was at the beginning of the 1990s. The total area of polluted water fluctuated without any trend from the end of the 1990s until 2015, but has declined sharply by nearly two-thirds since 2015, indicating that the water quality in China’s coastal seas has improved substantially. Geographically, the Bohai Sea was the first to see a turning point in water quality, followed by the Yellow Sea and East China Sea, while the South China Sea was the last. The main pollutants that govern the water quality grade and area are dissolved inorganic nitrogen and phosphate as well as petroleum hydrocarbons. As a response to variations in water quality, changes in both the frequency and total area affected by harmful algal blooms were similar to those of water quality over the last three decades, albeit with a slight lag. Analysis showed that variations in water quality were closely related to the land- and sea-sourced pollutant inputs. The combination of shift in the mode of economic growth from high-speed growth to high-quality development and the enforcement of the new, strictest ever Environmental Protection Law resulted in a significant decline of pollutant emissions, inducing a turning point in the water quality in the coastal seas of China in the mid-2010s.
Enrichment of rare methanogenic Archaea shows their important ecological role in natural high-CO2 terrestrial subsurface environments
Authors: Jia Zeyu , Lipus Daniel , Burckhardt Oliver , Bussert Robert , Sondermann Megan , Bartholomäus Alexander , Wagner Dirk , Kallmeyer Jens
Published: May 2023

Introduction

Long-term stability of underground CO2 storage is partially affected by microbial activity but our knowledge of these effects is limited, mainly due to a lack of sites. A consistently high flux of mantle-derived CO2 makes the Eger Rift in the Czech Republic a natural analogue to underground CO2 storage. The Eger Rift is a seismically active region and H2 is produced abiotically during earthquakes, providing energy to indigenous microbial communities.

Methods

To investigate the response of a microbial ecosystem to high levels of CO2 and H2, we enriched microorganisms from samples from a 239.5 m long drill core from the Eger Rift. Microbial abundance, diversity and community structure were assessed using qPCR and 16S rRNA gene sequencing. Enrichment cultures were set up with minimal mineral media and H2/CO2 headspace to simulate a seismically active period with elevated H2.

Results and discussion

Methane headspace concentrations in the enrichments indicated that active methanogens were almost exclusively restricted to enrichment cultures from Miocene lacustrine deposits (50–60 m), for which we observed the most significant growth. Taxonomic assessment showed microbial communities in these enrichments to be less diverse than those with little or no growth. Active enrichments were especially abundant in methanogens of the taxa Methanobacterium and Methanosphaerula. Concurrent to the emergence of methanogenic archaea, we also observed sulfate reducers with the metabolic ability to utilize H2 and CO2, specifically the genus Desulfosporosinus, which were able to outcompete methanogens in several enrichments. Low microbial abundance and a diverse non-CO2 driven microbial community, similar to that in drill core samples, also reflect the inactivity in these cultures. Significant growth of sulfate reducing and methanogenic microbial taxa, which make up only a small fraction of the total microbial community, emphasize the need to account for rare biosphere taxa when assessing the metabolic potential of microbial subsurface populations. The observation that CO2 and H2-utilizing microorganisms could only be enriched from a narrow depth interval suggests that factors such as sediment heterogeneity may also be important. This study provides new insight on subsurface microbes under the influence of high CO2 concentrations, similar to those found in CCS sites.
Microbial metabolic activity in Amazon floodplain forest and agricultural soils
Authors: Barros Dayane J. , Carvalho Glauber A. , de Chaves Miriam G. , Vanzela Luiz S. , Kozusny-Andreani Dora Inés , Guarda Emerson A. , Neu Vania , de Morais Paula B. , Tsai Siu M. , Navarrete Acacio A.
Published: May 2023

Microorganisms play an essential role in ecosystem functions. An increasingly used method for conducting functional analyses of a soil microbial community is based on the physiological profile at the community level. This method allows the metabolic capacity of microorganisms to be assessed based on patterns of carbon consumption and derived indices. In the present study, the functional diversity of microbial communities was assessed in soils from seasonally flooded-forest (FOR) and -traditional farming systems (TFS) in Amazonian floodplains flooded with black, clear, and white water. The soils of the Amazon floodplains showed differences in the metabolic activity of their microbial communities, with a general trend in activity level of clear water floodplain > black water floodplain > white water floodplain. The redundancy analysis (RDA) indicated that soil moisture (flood pulse) was the most important environmental parameter in determining the metabolic activity of the soil microbial communities in the black, clear, and white floodplains. In addition, the variance partitioning analysis (VPA) indicated that the microbial metabolic activity of the soil was more influenced by water type (41.72%) than by seasonality (19.55%) and land use type (15.28%). The soil microbiota of the white water floodplain was different from that of the clear water and black water floodplains in terms of metabolic richness, as the white water floodplain was mainly influenced by the low substrate use during the non-flooded period. Taken together, the results show the importance of considering soils under the influence of flood pulses, water types, and land use as environmental factors when recognizing functional diversity and ecosystem functioning in Amazonian floodplains.