bluuebunny/crossref_metadata_2025 huggingface dataset:
Metagenomic sequencing, molecular characterization, and Bayesian phylogenetics of imported type 2 vaccine-derived poliovirus, Spain, 2021
Authors: Fernandez-Garcia Maria Dolores , Faye Martin , Diez-Fuertes Francisco , Moreno-Docón Antonio , Chirlaque-López Maria Dolores , Faye Ousmane , Cabrerizo Maria
Published: May 2023

Introduction

In 2021, a type 2 vaccine-derived poliovirus (VDPV2) was isolated from the stool of a patient with acute flaccid paralysis (AFP) admitted to Spain from Senegal. A virological investigation was conducted to characterize and trace the origin of VDPV2.

Methods

We used an unbiased metagenomic approach for the whole-genome sequencing of VDPV2 from the stool (pre-treated with chloroform) and from the poliovirus-positive supernatant. Phylogenetic analyses and molecular epidemiological analyses relying on the Bayesian Markov Chain Monte Carlo methodology were used to determine the geographical origin and estimate the date of the initiating dose of the oral poliovirus vaccine for the imported VDPV2.

Results

We obtained a high percentage of viral reads per total reads mapped to the poliovirus genome (69.5% for pre-treated stool and 75.8% for isolate) with a great depth of sequencing coverage (5,931 and 11,581, respectively) and complete genome coverage (100%). The two key attenuating mutations in the Sabin 2 strain had reverted (A481G in the 5’UTR and Ile143Thr in VP1). In addition, the genome had a recombinant structure between type-2 poliovirus and an unidentified non-polio enterovirus-C (NPEV-C) strain with a crossover point in the protease-2A genomic region. VP1 phylogenetic analysis revealed that this strain is closely related to VDPV2 strains circulating in Senegal in 2021. According to Bayesian phylogenetics, the most recent common ancestor of the imported VDPV2 could date back 2.6 years (95% HPD: 1.7–3.7) in Senegal. We suggest that all VDPV2s circulating in 2020–21 in Senegal, Guinea, Gambia, and Mauritania have an ancestral origin in Senegal estimated around 2015. All 50 stool samples from healthy case contacts collected in Spain (n = 25) and Senegal (n = 25) and four wastewater samples collected in Spain were poliovirus negative.

Discussion

By using a whole-genome sequencing protocol with unbiased metagenomics from the clinical sample and viral isolate with high sequence coverage, efficiency, and throughput, we confirmed the classification of VDPV as a circulating type. The close genomic linkage with strains from Senegal was consistent with their classification as imported. Given the scarce number of complete genome sequences for NPEV-C in public databases, this protocol could help expand poliovirus and NPEV-C sequencing capacity worldwide.
Causal effects between gut microbiota and IgA nephropathy: a bidirectional Mendelian randomization study
Authors: Ren Feihong , Jin Qiubai , Liu Tongtong , Ren Xuelei , Zhan Yongli
Published: May 2023

Background

Therapeutic approaches that target the gut microbiota (GM) may be helpful in the potential prevention and treatment of IgA nephropathy (IgAN). Meanwhile, relevant studies demonstrated a correlation between GM and IgAN, however, these confounding evidence cannot prove a causal relationship between GM and IgAN.

Methods

Based on the data from the GM genome-wide association study (GWAS) of MiBioGen and the IgAN GWAS data from the FinnGen research. A bi-directional Mendelian randomization (MR) study was performed to explore the causal relationship between GM and IgAN. We used inverse variance weighted (IVW) method as the primary method to determine the causal relationship between exposure and outcome in our MR study. Besides, we used additional analysis (MR-Egger, weighted median) and sensitivity analysis (Cochrane’s Q test, MR-Egger and MR-PRESSO) to select significant results, followed by Bayesian model averaging (MR-BMA) to test the results of MR study. Finally, a reverse MR analysis was conducted to estimate the probability of reverse causality.

Results

At the locus-wide significance level, the results of IVW method and additional analysis showed that Genus Enterorhabdus was a protective factor for IgAN [OR: 0.456, 95% CI: 0.238-0.875, p=0.023], while Genus butyricicoccus was a risk factor for IgAN [OR: 3.471, 95% CI: 1.671-7.209, p=0.0008]. In the sensitivity analysis, no significant pleiotropy or heterogeneity of the results was found.

Conclusion

Our study revealed the causal relationship between GM and IgAN, and expanded the variety of bacterial taxa causally related to IgAN. These bacterial taxa could become novel biomarkers to facilitate the development of targeted therapies for IgAN, developing our understanding of the “gut-kidney axis”.
Intestinal loads of extended-spectrum beta-lactamase and Carbapenemase genes in critically ill pediatric patients
Authors: Dahdouh Elias , Cendejas-Bueno Emilio , Ruiz-Carrascoso Guillermo , Schüffelmann Cristina , Lázaro-Perona Fernando , Castro-Martínez Mercedes , Moreno-Ramos Francisco , Escosa-García Luis , Alguacil-Guillén Marina , Mingorance Jesús
Published: May 2023

Introduction

Intestinal colonization by Multi-Drug Resistant Organisms (MDROs) can pose a threat on the health of critically ill patients. The extent of colonization by these organisms is related to previous antibiotic treatments and their ability to cause infections among adult patients. The aim of this study is to determine the relationship between the intestinal Relative Loads (RLs) of selected antibiotic resistance genes, antibiotic consumption and extra-intestinal spread among critically ill pediatric patients.

Methods

RLs of blaCTX-M-1-Family, blaOXA-1, blaOXA-48 and blaVIM were determined in 382 rectal swabs obtained from 90 pediatric critically ill patients using qPCRs. The RLs were compared to the patients’ demographics, antibiotic consumption, and detection of MDROs from extra-intestinal sites. 16SrDNA metagenomic sequencing was performed for 40 samples and clonality analyses were done for representative isolates.

Results and discussion

76 (74.45%) patients from which 340 (89.01%) rectal swabs were collected had at least one swab that was positive for one of the tested genes. Routine cultures did not identify carbapenemases in 32 (45.1%) and 78 (58.2%) swabs that were positive by PCR for blaOXA-48 and blaVIM, respectively. RLs of above 6.5% were associated with extra-intestinal spread of blaOXA-48-harboring MDROs. Consumption of carbapenems, non-carbapenem β-lactams, and glycopeptides were statistically associated with testing negative for blaCTX-M-1-Family and blaOXA-1 while the consumption of trimethoprim/sulfamethoxazole and aminoglycosides was associated with testing negative for blaOXA-48 (P<0.05). In conclusion, targeted qPCRs can be used to determine the extent of intestinal dominance by antibiotic resistant opportunistic pathogens and their potential to cause extra-intestinal infections among a critically ill pediatric population.
An update on recent progress of the epidemiology, etiology, diagnosis, and treatment of acute septic arthritis: a review
Authors: He Miao , Arthur Vithran Djandan Tadum , Pan Linyuan , Zeng Haijin , Yang Guang , Lu Bangbao , Zhang Fangjie
Published: May 2023

Acute septic arthritis is on the rise among all patients. Acute septic arthritis must be extensively assessed, identified, and treated to prevent fatal consequences. Antimicrobial therapy administered intravenously has long been considered the gold standard for treating acute osteoarticular infections. According to clinical research, parenteral antibiotics for a few days, followed by oral antibiotics, are safe and effective for treating infections without complications. This article focuses on bringing physicians up-to-date on the most recent findings and discussions about the epidemiology, etiology, diagnosis, and treatment of acute septic arthritis. In recent years, the emergence of antibiotic-resistant, particularly aggressive bacterial species has highlighted the need for more research to enhance treatment approaches and develop innovative diagnosis methods and drugs that might combat better in all patients. This article aims to furnish radiologists, orthopaedic surgeons, and other medical practitioners with contemporary insights on the subject matter and foster collaborative efforts to improve patient outcomes. This review represents the initial comprehensive update encompassing patients across all age groups.
Genetic diversity and distinctiveness of Chilean Limachino tomato (Solanum lycopersicum L.) reveal an in situ conservation during the 20th century
Authors: Donoso Adolfo , Carrasco Basilio , Araya Carolina , Salazar Erika
Published: May 2023

Landraces constitute a valuable genetic pool of increased diversity that can be exploited for agriculture sustainability, food security, food quality, and future yield increments. It also contributes to understanding a species’ origin, domestication, population dynamics, and diversity. Chilean tomato germplasm characterization and documentation are scarce. To elucidate its potential and distinctiveness, we assessed the genetic variability between and within accessions of tomato landraces grown in Chile between 1938 and 2016, determining the relationships between them and with some European and US heirloom varieties. For this purpose, the tomato plants were characterized using 72 descriptors for vegetative and reproductive morphology. In addition, molecular diversity and the determination of genetic patterns between tomato accessions were made using highly informative SSR markers. Our results indicate that the genetic structure among evaluated accessions is associated with differences between the Chilean landraces grown to 1938 and cultivars grown in Europe and USA. The Chilean cluster presented a high variability. The Limachino tomato landrace is close to Marmande but distinguishable on phenotype and the molecular basis for its private alleles, being grown in the territory of Limache before 1960 until the present day. Accessions of pink beefsteak tomato grown in Chile to 2015 are distant to the rest of the tomato accessions on morphotype and close in SSR genotype to the materials grown in Chile in 1938, supporting the hypothesis of a pre-green revolution tomato diversification in Chilean territory. Chilean tomato populations may impact breeding programs due to higher variability in yield components. Our results are consistent with other researchers that have proposed Mesoamerica and the Andes Region as tomatoes’ primary center of diversity.
Treatment of pure aortic regurgitation using surgical or transcatheter aortic valve replacement between 2018 and 2020 in Germany
Authors: Oettinger Vera , Hilgendorf Ingo , Wolf Dennis , Stachon Peter , Heidenreich Adrian , Zehender Manfred , Westermann Dirk , Kaier Klaus , von zur Mühlen Constantin
Published: May 2023

Background

In pure aortic regurgitation, transcatheter aortic valve replacement (TAVR) is not yet used on a regular base. Due to constant development of TAVR, it is necessary to analyze current data.

Methods

By use of health records, we analyzed all isolated TAVR or surgical aortic valve replacements (SAVR) for pure aortic regurgitation between 2018 and 2020 in Germany.

Results

4,861 procedures—4,025 SAVR and 836 TAVR—for aortic regurgitation were identified. Patients treated with TAVR were older, showed a higher logistic EuroSCORE, and had more pre-existing diseases. While results indicate a slightly higher unadjusted in-hospital mortality for transapical TAVR (6.00%) vs. SAVR (5.71%), transfemoral TAVR showed better outcomes, with self-expanding compared to balloon-expandable transfemoral TAVR having significantly lower in-hospital mortality (2.41% vs. 5.17%; p = 0.039). After risk adjustment, balloon-expandable as well as self-expanding transfemoral TAVR were associated with a significantly lower mortality vs. SAVR (balloon-expandable: risk adjusted OR = 0.50 [95% CI 0.27; 0.94], p = 0.031; self-expanding: OR = 0.20 [0.10; 0.41], p < 0.001). Furthermore, the observed in-hospital outcomes of stroke, major bleeding, delirium, and mechanical ventilation >48 h were significantly in favor of TAVR. In addition, TAVR showed a significantly shorter length of hospital stay compared to SAVR (transapical: risk adjusted Coefficient = −4.75d [−7.05d; −2.46d], p < 0.001; balloon-expandable: Coefficient = −6.88d [−9.06d; −4.69d], p < 0.001; self-expanding: Coefficient = −7.22 [−8.95; −5.49], p < 0.001).

Conclusions

TAVR is a viable alternative to SAVR in the treatment of pure aortic regurgitation for selected patients, showing overall low in-hospital mortality and complication rates, especially with regard to self-expanding transfemoral TAVR.
Elementary school teachers’ perceptions of the characteristics of twice-exceptional students
Authors: Alsamani Omar Abdullah , Alsamiri Yasir Ayed , Alfaidi Seham Defallah
Published: May 2023

The current study explored the perceptions and understanding of Saudi elementary school teachers regarding the characteristics of twice-exceptional (2e) students. This qualitative phenomenological study recruited 14 elementary school teachers at schools in Medina City in Saudi Arabia. Data were gathered through in-depth semi-structured interviews to gain insight into participants’ perceptions of this student population. Findings indicated that teachers associate certain characteristics with the giftedness trait of 2e students, including excellent communication skills, problem-solving ability, strong retention, curiosity, creativity, abstract thinking, and leadership skills. Moreover, Saudi elementary school teachers perceive that 2e students experience academic challenges related to their disabilities in reading, writing, and mathematics, as well as are aware that such students tend to struggle with low self-esteem and maintaining concentration. Overall, there is a tendency to view these students as having two independent conditions—giftedness and disabilities that cause academic challenges—rather than identifying these individuals as having a single condition of being twice exceptional that comprises traits that impact their learning in combination.
The role of proteasome activators PA28αβ and PA200 in brown adipocyte differentiation and function
Authors: Koçberber Zeynep , Willemsen Nienke , Bartelt Alexander
Published: May 2023

Introduction

Brown adipocytes produce heat through non shivering thermogenesis (NST). To adapt to temperature cues, they possess a remarkably dynamic metabolism and undergo substantial cellular remodeling. The proteasome plays a central role in proteostasis and adaptive proteasome activity is required for sustained NST. Proteasome activators (PAs) are a class of proteasome regulators but the role of PAs in brown adipocytes is unknown. Here, we studied the roles of PA28α (encoded by Psme1) and PA200 (encoded by Psme4) in brown adipocyte differentiation and function.

Methods

We measured gene expression in mouse brown adipose tissue. In cultured brown adipocytes, we silenced Psme1 and/or Psme4 expression through siRNA transfection. We then assessed impact on the ubiquitin proteasome system, brown adipocyte differentiation and function.

Results

We found that Psme1 and Psme4 are expressed in brown adipocytes in vivo and in vitro. Through silencing of Psme1 and/or Psme4 expression in cultured brown adipocytes, we found that loss of PAs did not impair proteasome assembly or activity, and that PAs were not required for proteostasis in this model. Loss of Psme1 and/or Psme4 did not impair brown adipocyte development or activation, suggesting that PAs are neither required for brown adipogenesis nor NST.

Discussion

In summary, we found no role for Psme1 and Psme4 in brown adipocyte proteostasis, differentiation, or function. These findings contribute to our basic understanding of proteasome biology and the roles of proteasome activators in brown adipocytes.
Village ecosystem vulnerability in karst desertification control: evidence from South China Karst
Authors: Tang Jiuhan , Xiong Kangning , Wang Qi , Chen Yue , Wu Qinglin
Published: May 2023

Against the background of global environmental changes and the intensification of human activity, the village ecosystem faces enormous challenges. In particular, the rural areas in South China Karst face serious problems, such as karst desertification and human–land conflicts. In recent decades, the Chinese government and scientific researchers have committed to controlling karst desertification. However, village ecosystems in the context of karst desertification control (KDC) remain fragile. To promote the sustainable development of villages in KDC, this study considered village ecosystems in different karst desertification areas as study cases. Based on the model of susceptibility-exposure-lack of resilience, we constructed an index system of vulnerability research, used the entropy method to determine the weight, and introduced a contribution model to clarify the vulnerability level and vulnerability driving factors to recommend related governance strategies. We found that (1) the village ecosystem vulnerability levels under KDC were different. Village ecosystems were mildly vulnerable in none-potential KDC areas, moderately vulnerable in potential-mild areas, and moderately and highly vulnerable in moderate–severe KDC areas. (2) The combined effects of the natural environment and human activity have led to the vulnerability of village ecosystems in KDC in South China Karst. Among them, topography, climate, forest coverage, landscape pattern, soil erosion, karst desertification, economic development level, and production and living activity are the main factors affecting the village ecosystem vulnerability of KDC in South China Karst, and the differences in these factors lead to differences in vulnerability levels of different village ecosystems. (3) We designed adaptive governance strategies for village ecosystems based on the factors influencing the characteristics and vulnerability of different karst desertification areas, with the primary goal of sustainable development. They provide a decision-making basis for promoting sustainable development of the village ecosystems in KDC.
Genus-level macroinvertebrate methods limit the conservation coverage afforded aquatic species
Authors: Robinson Jason L.
Published: May 2023

Benthic macroinvertebrate protocols, in the United States, have been integral in the implementation of the Clean Water Act (33 U.S.C. §1251 et seq. (1972)). The methods in these protocols are designed to describe patterns of biological water quality and ecological condition relevant to legislative oversight, and require a tradeoff between taxonomic precision and protocol simplicity. The global similarity of ecological and evolutionary responses to the challenges of life in flowing waters, by stream organisms, has greatly facilitated the development and implementation of biological data from freshwater mussels, fishes and aquatic insects into streamlined regulatory frameworks. Unfortunately, the factors that expedite the use of benthic data into ecological descriptions sufficient for regulatory processes (taxonomic generalizations, standardization of sampling procedures to focus on a narrow subset of available habitats) also limit the utility of these methods in the conservation of benthic macroinvertebrate species (the large majority of which are insects). Using simple hypothetical simulations, some examples from a taxonomic and ecological database of one state in the USA (Illinois), and data from a large-scale inventory of aquatic insect species in a network of US National Parks, I illustrate how these methods are limited in their ability to effectively describe ecological patterns relevant to the conservation of aquatic insect species. I identify, challenge, and explore three basic assumptions implicit to the genus- and family-level identification methods widely used in freshwater benthic science, then discuss how the failure of these assumptions may create empirical, theoretical and philosophical obstacles to the interpretation of data and certainly hinder the conservation of species. I offer some hopeful suggestions for improving aquatic insect species conservation that are within the reach of all benthic freshwater ecologists.
Gene expression networks and functionally enriched pathways involved in the response of domestic chicken to acute heat stress
Authors: Hosseinzadeh Sevda , Hasanpur Karim
Published: May 2023

Heat stress in poultry houses, especially in warm areas, is one of the main environmental factors that restrict the growth of broilers or laying performance of layers, suppresses the immune system, and deteriorates egg quality and feed conversion ratio. The molecular mechanisms underlying the response of chicken to acute heat stress (AHS) have not been comprehensively elucidated. Therefore, the main object of the current work was to investigate the liver gene expression profile of chickens under AHS in comparison with their corresponding control groups, using four RNA-seq datasets. The meta-analysis, GO and KEGG pathway enrichment, WGCNA, machine-learning, and eGWAS analyses were performed. The results revealed 77 meta-genes that were mainly related to protein biosynthesis, protein folding, and protein transport between cellular organelles. In other words, under AHS, the expression of genes involving in the structure of rough reticulum membrane and in the process of protein folding was adversely influenced. In addition, genes related to biological processes such as “response to unfolded proteins,” “response to reticulum stress” and “ERAD pathway” were differentially regulated. We introduce here a couple of genes such as HSPA5, SSR1, SDF2L1, and SEC23B, as the most significantly differentiated under AHS, which could be used as bio-signatures of AHS. Besides the mentioned genes, the main findings of the current work may shed light to the identification of the effects of AHS on gene expression profiling of domestic chicken as well as the adaptive response of chicken to environmental stresses.
Identification and validation of a novel stress granules-related prognostic model in colorectal cancer
Authors: Liu Zhihao , Zhao Enen , Li Huali , Lin Dagui , Huang Chengmei , Zhou Yi , Zhang Yaxin , Pan Xingyan , Liao Wenting , Li Fengtian
Published: May 2023

Aims: A growing body of evidence demonstrates that Stress granules (SGs), a non-membrane cytoplasmic compartments, are important to colorectal development and chemoresistance. However, the clinical and pathological significance of SGs in colorectal cancer (CRC) patients is unclear. The aim of this study is to propose a new prognostic model related to SGs for CRC on the basis of transcriptional expression.

Main methods: Differentially expressed SGs-related genes (DESGGs) were identified in CRC patients from TCGA dataset by limma R package. The univariate and Multivariate Cox regression model was used to construct a SGs-related prognostic prediction gene signature (SGPPGS). The CIBERSORT algorithm was used to assess cellular immune components between the two different risk groups. The mRNA expression levels of the predictive signature from 3 partial response (PR) and 6 stable disease (SD) or progress disease (PD) after neoadjuvant therapy CRC patients’ specimen were examined.

Key findings: By screening and identification, SGPPGS comprised of four genes (CPT2, NRG1, GAP43, and CDKN2A) from DESGGs is established. Furthermore, we find that the risk score of SGPPGS is an independent prognostic factor to overall survival. Notably, the abundance of immune response inhibitory components in tumor tissues is upregulated in the group with a high-risk score of SGPPGS. Importantly, the risk score of SGPPGS is associated with the chemotherapy response in metastatic colorectal cancer.

Significance: This study reveals the association between SGs related genes and CRC prognosis and provides a novel SGs related gene signature for CRC prognosis prediction.
KISL: knowledge-injected semi-supervised learning for biological co-expression network modules
Authors: Xiao Gangyi , Guan Renchu , Cao Yangkun , Huang Zhenyu , Xu Ying
Published: May 2023

The exploration of important biomarkers associated with cancer development is crucial for diagnosing cancer, designing therapeutic interventions, and predicting prognoses. The analysis of gene co-expression provides a systemic perspective on gene networks and can be a valuable tool for mining biomarkers. The main objective of co-expression network analysis is to discover highly synergistic sets of genes, and the most widely used method is weighted gene co-expression network analysis (WGCNA). With the Pearson correlation coefficient, WGCNA measures gene correlation, and uses hierarchical clustering to identify gene modules. The Pearson correlation coefficient reflects only the linear dependence between variables, and the main drawback of hierarchical clustering is that once two objects are clustered together, the process cannot be reversed. Hence, readjusting inappropriate cluster divisions is not possible. Existing co-expression network analysis methods rely on unsupervised methods that do not utilize prior biological knowledge for module delineation. Here we present a method for identification of outstanding modules in a co-expression network using a knowledge-injected semi-supervised learning approach (KISL), which utilizes apriori biological knowledge and a semi-supervised clustering method to address the issue existing in the current GCN-based clustering methods. To measure the linear and non-linear dependence between genes, we introduce a distance correlation due to the complexity of the gene-gene relationship. Eight RNA-seq datasets of cancer samples are used to validate its effectiveness. In all eight datasets, the KISL algorithm outperformed WGCNA when comparing the silhouette coefficient, Calinski-Harabasz index and Davies-Bouldin index evaluation metrics. According to the results, KISL clusters had better cluster evaluation values and better gene module aggregation. Enrichment analysis of the recognition modules demonstrated their effectiveness in discovering modular structures in biological co-expression networks. In addition, as a general method, KISL can be applied to various co-expression network analyses based on similarity metrics. Source codes for the KISL and the related scripts are available online at https://github.com/Mowonhoo/KISL.git.
A self-binding immune complex vaccine elicits strong neutralizing responses against herpes simplex virus in mice
Authors: Diamos Andrew G. , Pardhe Mary D. , Bergeman Melissa H. , Kamzina Aigerim S. , DiPalma Michelle P. , Aman Sara , Chaves Artemio , Lowe Kenneth , Kilbourne Jacquelyn , Hogue Ian B. , Mason Hugh S.
Published: May 2023

Introduction

It has been known for over half a century that mixing an antigen with its cognate antibody in an immune complex (IC) can enhance antigen immunogenicity. However, many ICs produce inconsistent immune responses, and the use of ICs in the development new vaccines has been limited despite the otherwise widespread success of antibody-based therapeutics. To address this problem, we designed a self-binding recombinant immune complex (RIC) vaccine which mimics the larger ICs generated during natural infection.

Materials and methods

In this study, we created two novel vaccine candidates: 1) a traditional IC targeting herpes simplex virus 2 (HSV-2) by mixing glycoprotein D (gD) with a neutralizing antibody (gD-IC); and 2) an RIC consisting of gD fused to an immunoglobulin heavy chain and then tagged with its own binding site, allowing self-binding (gD-RIC). We characterized the complex size and immune receptor binding characteristics in vitro for each preparation. Then, the in vivo immunogenicity and virus neutralization of each vaccine were compared in mice.

Results

gD-RIC formed larger complexes which enhanced C1q receptor binding 25-fold compared to gD-IC. After immunization of mice, gD-RIC elicited up to 1,000-fold higher gD-specific antibody titers compared to traditional IC, reaching endpoint titers of 1:500,000 after two doses without adjuvant. The RIC construct also elicited stronger virus-specific neutralization against HSV-2, as well as stronger cross-neutralization against HSV-1, although the proportion of neutralizing antibodies to total antibodies was somewhat reduced in the RIC group.

Discussion

This work demonstrates that the RIC system overcomes many of the pitfalls of traditional IC, providing potent immune responses against HSV-2 gD. Based on these findings, further improvements to the RIC system are discussed. RIC have now been shown to be capable of inducing potent immune responses to a variety of viral antigens, underscoring their broad potential as a vaccine platform.
Atractylodes macrocephala Koidz. volatile oil relieves acute ulcerative colitis via regulating gut microbiota and gut microbiota metabolism
Authors: Cheng Hao , Zhang Dandan , Wu Jing , Liu Juan , Tan Yuzhu , Feng Wuwen , Peng Cheng
Published: May 2023

Background

Atractylodes macrocephala Koidz. (AM) is a functional food with strong ant-colitis activity. AM volatile oil (AVO) is the main active ingredient of AM. However, no study has investigated the improvement effect of AVO on ulcerative colitis (UC) and the bioactivity mechanism also remains unknown. Here, we investigated whether AVO has ameliorative activity on acute colitis mice and its mechanism from the perspective of gut microbiota.

Methods

Acute UC was induced in C57BL/6 mice by dextran sulfate sodium and treated with the AVO. Body weight, colon length, colon tissue pathology, and so on were assessed. The gut microbiota composition was profiled using 16s rRNA sequencing and global metabolomic profiling of the feces was performed. The results showed that AVO can alleviate bloody diarrhea, colon damage, and colon inflammation in colitis mice. In addition, AVO decreased potentially harmful bacteria (Turicibacter, Parasutterella, and Erysipelatoclostridium) and enriched potentially beneficial bacteria (Enterorhabdus, Parvibacter, and Akkermansia). Metabolomics disclosed that AVO altered gut microbiota metabolism by regulating 56 gut microbiota metabolites involved in 102 KEGG pathways. Among these KEGG pathways, many metabolism pathways play an important role in maintaining intestine homeostasis, such as amino acid metabolism (especially tryptophan metabolism), bile acids metabolism, and retinol metabolism.

Conclusion

In conclusion, our study indicated that AVO can be expected as novel prebiotics to treat ulcerative colitis, and modulating the composition and metabolism of gut microbiota may be its pharmacological mechanism.
Inhibition of the intracellular domain of Notch1 results in vascular endothelial cell dysfunction in sepsis
Authors: Liu Tingyan , Zhang Caiyan , Ying Jiayun , Wang Yaodong , Yan Gangfeng , Zhou Yufeng , Lu Guoping
Published: May 2023

Background

Notch signaling is critical for regulating the function of vascular endothelial cells (ECs). However, the effect of the intracellular domain of Notch1 (NICD) on EC injury in sepsis remains unclear.

Methods

We established a cell model of vascular endothelial dysfunction and induced sepsis in a mouse model via lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP). Endothelial barrier function and expression of endothelial-related proteins were determined using CCK-8, permeability, flow cytometry, immunoblot, and immunoprecipitation assays. The effect of NICD inhibition or activation on endothelial barrier function was evaluated in vitro. Melatonin was used for NICD activation in sepsis mice. The survival rate, Evans blue dye of organs, vessel relaxation assay, immunohistochemistry, ELISA, immunoblot were used to explore the specific role of melatonin for sepsis induced vascular dysfunction in vivo.

Results

We found that LPS, interleukin 6, and serum collected from septic children could inhibit the expression of NICD and its downstream regulator Hes1, which impaired endothelial barrier function and led to EC apoptosis through the AKT pathway. Mechanistically, LPS decreased the stability of NICD by inhibiting the expression of a deubiquitylating enzyme, ubiquitin-specific proteases 8 (USP8). Melatonin, however, upregulated USP8 expression, thus maintaining the stability of NICD and Notch signaling, which ultimately reduced EC injury in our sepsis model and elevated the survival rate of septic mice.

Conclusions

We found a previously uncharacterized role of Notch1 in mediating vascular permeability during sepsis, and we showed that inhibition of NICD resulted in vascular EC dysfunction in sepsis, which was reversed by melatonin. Thus, the Notch1 signaling pathway is a potential target for the treatment of sepsis.
Cellular and molecular insights into incomplete immune recovery in HIV/AIDS patients
Authors: Yan Liting , Xu Kaiju , Xiao Qing , Tuo Lin , Luo Tingting , Wang Shuqiang , Yang Renguo , Zhang Fujie , Yang Xingxiang
Published: May 2023

Highly active antiretroviral therapy (ART) can effectively inhibit virus replication and restore immune function in most people living with human immunodeficiency virus (HIV). However, an important proportion of patients fail to achieve a satisfactory increase in CD4+ T cell counts. This state is called incomplete immune reconstitution or immunological nonresponse (INR). Patients with INR have an increased risk of clinical progression and higher rates of mortality. Despite widespread attention to INR, the precise mechanisms remain unclear. In this review, we will discuss the alterations in the quantity and quality of CD4+ T as well as multiple immunocytes, changes in soluble molecules and cytokines, and their relationship with INR, aimed to provide cellular and molecular insights into incomplete immune reconstitution.
Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy
Authors: Kilgour Marisa K. , Bastin Donald J. , Lee Seung-Hwan , Ardolino Michele , McComb Scott , Visram Alissa
Published: May 2023

Advancements in chimeric antigen receptor engineered T-cell (CAR-T) therapy have revolutionized treatment for several cancer types over the past decade. Despite this success, obstacles including the high price tag, manufacturing complexity, and treatment-associated toxicities have limited the broad application of this therapy. Chimeric antigen receptor engineered natural killer cell (CAR-NK) therapy offers a potential opportunity for a simpler and more affordable “off-the-shelf” treatment, likely with fewer toxicities. Unlike CAR-T, CAR-NK therapies are still in early development, with few clinical trials yet reported. Given the challenges experienced through the development of CAR-T therapies, this review explores what lessons we can apply to build better CAR-NK therapies. In particular, we explore the importance of optimizing the immunochemical properties of the CAR construct, understanding factors leading to cell product persistence, enhancing trafficking of transferred cells to the tumor, ensuring the metabolic fitness of the transferred product, and strategies to avoid tumor escape through antigen loss. We also review trogocytosis, an important emerging challenge that likely equally applies to CAR-T and CAR-NK cells. Finally, we discuss how these limitations are already being addressed in CAR-NK therapies, and what future directions may be possible.
Rapid changes in the surface carbonate system under complex mixing schemes across the Bering Sea: a comparative study of a forward voyage in July and a return voyage in September 2018
Authors: Yang Wei , Wu Yingxu , Cai Wei-Jun , Ouyang Zhangxian , Zhuang Yanpei , Chen Liqi , Qi Di
Published: May 2023

Regulated by the rapid changes in temperature, mixing, and biological production during warm seasons, the surface carbonate system in the Bering Sea is subject to significant spatial-temporal variability. However, the seasonal evolution of the carbon cycle and its controls are less clear due to the lack of observations. Here, we present the carbonate data collected during a forward voyage in July and a return voyage in September 2018 across the Bering Sea. For both voyages, we show distinct dissolved inorganic carbon versus total alkalinity (DIC-TA) relationships and partial pressure of CO2 (pCO2) distribution patterns in the Southern Basin (54-57°N), the Northern Basin (57-59°N), the Slope (59-61°N), the Shelf (61-64°N), and the Bering Strait (>64°N). In the Southern Basin, the Northern Basin, and the Slope, surface water was a two end-member mixing of Rainwater and Bering Summer Water (BSW) during the forward voyage and a two end-member mixing of North Pacific Surface Water (NPSW) and BSW during the return voyage. As a result, the observed DIC was almost consistent with the conservative mixing line, with a slight DIC addition/removal of -8.6~5.8 µmol kg-1, suggesting low biological production/respiration during both voyages. Seasonally, the higher factions of NPSW featuring low pCO2 during the return voyage dominated the pCO2 drawdown from July to September in the Southern Basin and the Slope. On the Shelf, the surface water was a two end-member mixing of plume water from the Anadyr River and BSW during both voyages, but the decreased DIC consumption via biological production from 59.9 ± 25.8 µmol kg-1 to 34.8 ± 14.0 µmol kg-1 contributed to the pCO2 increase from July to September. In the Bering Strait, the coastal area was characterized by the influence of plume water from the Anadyr River in July and the coastal upwelling in September. The high biological production in plume water made a strong CO2 sink during the forward voyage, while the upwelling of carbon-enriched subsurface water with minor DIC consumption made the coastal ecosystem a strong CO2 source during the return voyage. In different geographical regions, the observed seawater pCO2 was much lower than the overlying atmospheric CO2, resulting in a net CO2 sink with fluxes of -2.1~-14.0 mmol m-2 d-1 and -2.5~-11.6 mmol m-2 d-1, respectively, during the forward and return voyages.
Monitoring and assessing the species diversity and abundance of marine teleost around the Yellow River estuary in June using environmental DNA
Authors: Lyu Ding , Qian Tangyi , Li Fan , Sun Song , Wang Weiji , Shan Xiujuan
Published: May 2023

The Yellow River estuary is an important feeding, reproduction, and development ground for a variety of marine economic species, and understanding the changes in species composition and abundance around the Yellow River estuary is of great significance. In this study, a trawl survey and seawater eDNA survey were carried out simultaneously around the Yellow River estuary with the objective of both understanding the composition of marine teleost around the Yellow River estuary and providing a reference for the application of eDNA in fishery resources surveys. The results showed that 31 species of marine teleost in total were detected using the trawl survey, and 33 species were detected using eDNA technology. The number of species detected by both methods was 21. In these 21 species, the Pearson’s correlation coefficients between their eDNA relative abundance and catch per unit effort (CPUE) were very high (0.993 for weight and 0.993 for quantity), while the Spearman’s correlation coefficients were 0.659 and 0.595, respectively. There were significant positive correlations between the biomass of specific species and their eDNA relative abundance. Species composition difference analysis based on eDNA showed that the species compositions of two low-salinity and low-water-depth survey stations were distinctly different from the others. This study not only scientifically monitors and evaluates the species diversity and abundance of teleost around the Yellow River estuary but also provides a reference for the application of eDNA in fishery resources surveys.
Aquatic species shows asymmetric distribution range shifts in native and non-native areas
Authors: Costa Eudriano F. S. , Encarnação João , Teodósio Maria Alexandra , Morais Pedro
Published: May 2023

Introduction

Climate change is reshaping the geographical distribution of species across the globe. In marine ecosystems, climate change creates novel challenges to an environment impacted by numerous anthropogenic stressors. Forecasting shifts in species distribution, including the expansion of non-indigenous species under climate change scenarios, is a management challenge for today’s world.

Methods

We applied Bayesian Additive Regression Tree (BART) models to investigate the environmental factors modulating the occurrence and habitat preferences of the Atlantic blue crab Callinectes sapidus Rathbun, 1896 in native and non-native areas. With BART models, we also aimed to predict its current and future distributions under two climate change scenarios (RCPs 4.5 and 8.5). BART models were performed using global occurrences of the Atlantic blue crab – recorded from 1830 to 2022 – and several environmental covariates (i.e., water temperature, salinity, current velocity, and rugosity). Model accuracy was assessed with the Area Under the Curve (AUC) and True Skill Statistics (TSS) criteria. Cross-validation experiments were made to balance accuracy prediction and uncertainty model prediction intervals.

Results and discussion

AUC and TSS values indicated that data validation was successful for the BART model. Water temperature was the most critical variable affecting the presence probability of the Atlantic blue crab. The BART model predicts asymmetric distribution range shifts on both sides of the Atlantic Ocean. The non-native populations will experience broader shifts in their distribution range than in the native range, and the RCP 8.5 scenario model outputs predict a wider distribution range by the end of the century. Overall, we anticipate significant ecological changes in native and non-native areas. The range expansion in native areas is often equivalent to the ecological shifts induced by invasive species, so lessons learned by ecologists and managers in non-native areas will provide actionable insights to managers in native areas.
Upwelling processes driven by contributions from wind and current in the Southwest East Sea (Japan Sea)
Authors: Kim Deoksu , Choi Jang-Geun , Park Jinku , Kwon Jae-Il , Kim Myeong-Hyeon , Jo Young-Heon
Published: May 2023

The occurrence of coastal upwelling is influenced by the intensity and duration of sea surface wind stress and geophysical components such as vertical stratification, bottom topography, and the entrainment of water masses. In addition, strong alongshore currents can drive upwelling. Accordingly, this study analyzes how wind stress and ocean currents contribute to changing coastal upwelling along the southwest coast of the East Sea (Japan Sea), which has not yet been reported quantitatively. This study aims to estimate each geophysical factor affecting upwelling processes using the Upwelling Age index. The index assesses the major contributors to the upwelling process using the relationship between physical forcing and upwelling water fraction estimated from shipboard hydrographic data from January 1993 to October 2018. These findings reveal that wind-driven upwelling was dominant off the northern coast. In contrast, current-driven upwelling prevailed off the southern coast. These results suggest that persistent alongshore currents through the Korea Strait make the southern region a prolific upwelling area. Accordingly, it can shed light on the mechanisms of coastal upwelling in the study area, which is crucial for understanding the influence of physical forces on ocean ecosystems.
Microbe-assisted seedling crop improvement by a seaweed extract to address fucalean forest restoration
Authors: Malfatti Francesca , Kaleb Sara , Saidi Amira , Pallavicini Alberto , Agostini Laura , Gionechetti Fabrizia , Natale Sara , Balestra Cecilia , Bevilacqua Stanislao , Falace Annalisa
Published: May 2023

In the Mediterranean, Cystoseira sensu lato (s.l.) (Phaeophyceae) forests have sharply declined and restoration measures are needed to compensate for the loss. Assisted regeneration through the outplanting of seedlings grown ex-situ has proven to be a sustainable option. Optimizing mesocosm culture can maximize survival of the most critical embryonic stages and reduce long-term maintenance costs. Host-microbiome interactions could also play a crucial role in seedling development and welfare. In this context, we aimed to advance a cultivation protocol that stimulates the growth and fitness of Ericaria amentacea (Phaeophyceae) seedlings and identify the associated microbial biofilm communities. Seedlings were cultured in 6 treatments [i.e., filtered seawater (SW, C, Control), von Stoch-enriched SW (VS), VS + algal extract (VSA), algal extract-enriched SW: A1< A2< A3]. After the field, A2 seedlings had the highest cover (1372 ± 53.66 mm2), which was 1.8 and 1.9 times greater than in VS and VSA, respectively. The addition of the algal extract and nutrients significantly affected the structure and composition of the microbial community that shifted over time in each culture medium. We identified a treatment-specific microbial fingerprint. After the mesocosm phase, A2 was characterized by 4 unique taxa: Postechiella, Winogradskyella, Roseovarius and Arenibacter (Bacteria). Given the success of A2 seedlings, we propose the probiotic consortia candidates characterized by the unique treatment-taxa in conjunction with the shared taxon Psychroserpens (Bacteria, present in A1, A2, VSA, VS) and the reminder community. Within the holobiont concept, the effect of algal extract or nutrients on the algae and/or biofilm could have important consequences for tuning the overall interaction networks. Our study has shown that macroalgal restoration could benefit from both the use of commercial algal extract and tailored nutrient enrichment in ex-situ cultures and the identification of probiotic consortia candidates that promote seedling growth.
Emerging nanomaterials to enhance electrochemical impedance spectroscopy for biomedical applications
Authors: Chen Justin , Arianpour Brian , Wang Kaidong , Wang Shaolei , Yin Junyi , Zhang Yaran , Zhu Enbo , Hsiai Tzung K.
Published: May 2023

Over the last few decades, electrical impedance-based sensors have been investigated for clinical translation to detect changes in tissue conductivities, including cardiac output and pulmonary function. Recently, electrochemical impedance spectroscopy (EIS) provides metabolic measurements that occur at the electrode-tissue interface, and the 3-D EIS can be reconstructed to generate electrical impedance tomography (EIT) for detecting the impedimetric properties of the vascular wall or fatty liver disease. In both EIS and EIT applications, the electrochemical properties of the interface electrodes are essential to address the signal-to-noise ratio or sensitivity of measurements in the biological environment. To enhance the conductive properties, we will survey a series of carbon-based nanomaterials as the emerging candidates for coating the electrodes of bioimpedance sensors. In this review, we will provide a theoretical background on impedance-based measurements and highlight the current state of EIS and EIT, including their applications for cancer screening and detection of vulnerable atherosclerotic plaques. Next, we will focus on the strengths of different nanomaterials when used as an electrode coating to optimize charge transfer across the electric double layers and to enhance measurement sensitivity. We will also identify some unmet clinical needs, such as the ability to adapt to different hemodynamic conditions and blood vessel geometries, that can be realized by the novel biomaterials for the future EIS-based sensors.