bluuebunny/crossref_metadata_2025 huggingface dataset:
As plantas representadas como mascotes dos times brasileiros de futebol
Authors: Brandão Lucas de Esquivel Dias , Rodrigues Hanna Thays Soares , Barros Marcelo Diniz Monteiro de
Published: March 2024

Uma pesquisa foi realizada na homepage: http://www.escudosdeclubes.com.br/, no ano de 2014, para verificar as mascotes dos times brasileiros de futebol da primeira, segunda, e daqueles times abaixo da segunda divisão (3º, 4º), das seguintes regiões brasileiras: Norte (N), Nordeste (NE), Sudeste (SE), Centro-Oeste (CO) e Sul (S). Encontrou-se um total de 627 times de futebol, dos quais apenas 12 times (1,9%) possuem como mascotes representantes do reino Plantae, e dessas, somente 3 nativas do nosso paí­s, que são o babaçu, o juazeiro e o mandacaru. Além disso, uma atividade contendo 14 questões dissertativas foi desenvolvida para alunos do Ensino Médio com o intuito de trabalhar os aspectos biológicos dos vegetais aqui apresentados. Espera-se que os professores de Biologia tenham acesso a essa atividade e que possam trabalhar os conteúdos de Biologia nelas existentes, como por exemplo, questões socioeconômicas, ecológicas, botânicas e culturais das plantas que são representadas como mascotes dos times brasileiros de futebol, de uma forma holí­stica. Almeja-se, ainda, que os mesmos possam desenvolver outras atividades como essa, em suas práticas educativas.Palavras chave: Ensino de Biologia, Ensino de Botânica, Mascotes de times de futebol.
Recursos complementares no ensino-aprendizagem da fisiologia dos potenciais elétricos do coração
Authors: Albuquerque Fabiola da Silva , Gouveia Rachel Linka Beniz , Cantalice Temilce SimÃµes de Assis , Oliveira Júnior Francisco Antônio de
Published: March 2024

Diante dos desafios atuais do processo ensino-aprendizagem, principalmente envolvendo conteúdos complexos e rico em detalhes, docentes da Disciplina de Fisiologia do DFP/CCS/UFPB vem desenvolvendo recursos complementares de estudo, denominados de maquetes, e o objetivo desse trabalho foi investigar a contribuição deles para a aprendizagem dos potenciais elétricos envolvidos no automatismo cardí­aco. Para isto, 119 estudantes de seis diferentes cursos responderam a testes sobre o tema antes e depois de utilizarem as maquetes. No teste antes das maquetes, estudantes de psicologia obtiveram desempenho melhor do que os demais, mas no resultado depois, todos os cursos foram equivalentes. O desempenho no teste depois da aplicação das maquetes foi significativamente melhor do que antes. Sugerimos que as maquetes podem ter fornecido um elemento concreto acessí­vel à percepção de que a complexidade do assunto poderia ser superada e contribuí­ram para engajar os alunos na responsabilidade pela construção do seu próprio conhecimento, favorecendo a aprendizagem.
Conceitos, procedimentos e atitudes na formação inicial: propostas para o ensino da cidadania
Authors: Pasquarelli Bruno , Benetti de Oliveira Thais
Published: March 2024

O estudo parte do pressuposto de que conceitos, procedimentos e atitudes sejam incluí­dos e concebidos como modalidades curriculares, sendo inseridos de maneira equitativa no planejamento e na ação docente. Isso porque cada modalidade curricular possui importância para a aquisição de uma aprendizagem integrada e articulada com temas especí­ficos. Nesse í­nterim, o objetivo central deste estudo é abordar a análise do conceito de cidadania a partir da aprendizagem das três modalidades curriculares, enfatizando sua importância nos processos de ensino no que tange ao planejamento, sistematização e proposição de abordagens pedagógicas. Para tanto, propõe-se que o ensino de conceitos, procedimentos e atitudes seja trabalhado de maneira equitativa na formação inicial, considerando aspectos de cidadania e de responsabilidade social, conjugando ações pedagógicas voltadas a um ensino integrado e que contemple outros objetivos além da memorização de dados.
Ten common issues with reference sequence databases and how to mitigate them
Authors: Chorlton Samuel D.
Published: March 2024

Metagenomic sequencing has revolutionized our understanding of microbiology. While metagenomic tools and approaches have been extensively evaluated and benchmarked, far less attention has been given to the reference sequence database used in metagenomic classification. Issues with reference sequence databases are pervasive. Database contamination is the most recognized issue in the literature; however, it remains relatively unmitigated in most analyses. Other common issues with reference sequence databases include taxonomic errors, inappropriate inclusion and exclusion criteria, and sequence content errors. This review covers ten common issues with reference sequence databases and the potential downstream consequences of these issues. Mitigation measures are discussed for each issue, including bioinformatic tools and database curation strategies. Together, these strategies present a path towards more accurate, reproducible and translatable metagenomic sequencing.
Functional analysis of a first hindlimb positioning enhancer via Gdf11 expression
Authors: Saito Seiji , Kanazawa Utsugi , Tatsumi Ayana , Iida Atsuo , Takemoto Tatsuya , Suzuki Takayuki
Published: March 2024

During the early development of tetrapods, including humans, the embryonic body elongates caudally once the anterior-posterior axis is established. During this process, region-specific vertebral morphogenesis occurs, with the determination of limb positioning along the anterior-posterior axis. We previously reported that Gdf11 functions as an anatomical integration system that determines the positioning of hindlimbs and sacral vertebrae where Gdf11 is expressed. However, the molecular mechanisms underlying induction of Gdf11 expression remain unclear. In this study, we searched for non-coding regions near the Gdf11 locus that were conserved across species to elucidate the regulatory mechanisms of Gdf11 expression. We identified an enhancer of the Gdf11 gene in intron 1 and named it highly conserved region (HCR). In HCR knockout mice, the expression level of endogenous Gdf11 was decreased, and the position of the sacral-hindlimb unit was shifted posteriorly. We also searched for factors upstream of Gdf11 based on the predicted transcription factor binding sites within the HCR. We found that inhibition of FGF signaling increased endogenous Gdf11 expression, suggesting that FGF signaling negatively regulates Gdf11 expression. However, FGF signaling does not regulate HCR activity. Our results suggest that there are species-specific Gdf11 enhancers other than HCR and that FGF signaling regulates Gdf11 expression independent of HCR.
Collective effects of cell cleavage dynamics
Authors: Schindler-Johnson Magdalena , Petridou Nicoletta I.
Published: March 2024

A conserved process of early embryonic development in metazoans is the reductive cell divisions following oocyte fertilization, termed cell cleavages. Cell cleavage cycles usually start synchronously, lengthen differentially between the embryonic cells becoming asynchronous, and cease before major morphogenetic events, such as germ layer formation and gastrulation. Despite exhibiting species-specific characteristics, the regulation of cell cleavage dynamics comes down to common controllers acting mostly at the single cell/nucleus level, such as nucleus-to-cytoplasmic ratio and zygotic genome activation. Remarkably, recent work has linked cell cleavage dynamics to the emergence of collective behavior during embryogenesis, including pattern formation and changes in embryo-scale mechanics, raising the question how single-cell controllers coordinate embryo-scale processes. In this review, we summarize studies across species where an association between cell cleavages and collective behavior was made, discuss the underlying mechanisms, and propose that cell-to-cell variability in cell cleavage dynamics can serve as a mechanism of long-range coordination in developing embryos.
On the uncertainty of long-period return values of extreme daily precipitation
Authors: Wehner Michael F. , Duffy Margaret L. , Risser Mark , Paciorek Christopher J. , Stone Dáithí A. , Pall Pardeep
Published: March 2024

Methods for calculating return values of extreme precipitation and their uncertainty are compared using daily precipitation rates over the Western U.S. and Southwestern Canada from a large ensemble of climate model simulations. The roles of return-value estimation procedures and sample size in uncertainty are evaluated for various return periods. We compare two different generalized extreme value (GEV) parameter estimation techniques, namely L-moments and maximum likelihood (MLE), as well as empirical techniques. Even for very large datasets, confidence intervals calculated using GEV techniques are narrower than those calculated using empirical methods. Furthermore, the more efficient L-moments parameter estimation techniques result in narrower confidence intervals than MLE parameter estimation techniques at small sample sizes, but similar best estimates. It should be noted that we do not claim that either parameter fitting technique is better calibrated than the other to estimate long period return values. While a non-stationary MLE methodology is readily available to estimate GEV parameters, it is not for the L-moments method. Comparison of uncertainty quantification methods are found to yield significantly different estimates for small sample sizes but converge to similar results as sample size increases. Finally, practical recommendations about the length and size of climate model ensemble simulations and the choice of statistical methods to robustly estimate long period return values of extreme daily precipitation statistics and quantify their uncertainty.
Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats
Authors: Elmahdy Ahmed , Shekka Espinosa Aaron , Kakaei Yalda , Pylova Tetiana , Jha Abhishek , Zulfaj Ermir , Krasnikova Maryna , Al-Awar Amin , Sheybani Zahra , Sevastianova Valentyna , Berger Evelin , Nejat Amirali , Molander Linnea , Andersson Erik Axel , Omerovic Elmir , Hussain Shafaat , Redfors Björn
Published: March 2024

Background and aims

Ischemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial stunning refers to transient loss of contractility in the heart after myocardial ischemia that recovers without permanent damage. The relationship between IPC and myocardial stunning remains incompletely understood. This study aimed primarily to examine the effects of IPC on the relationship between ischemia duration, stunning, and infarct size in an ischemia-reperfusion injury model. Secondarily, this study aimed to examine to which extent the phosphoproteomic changes induced by IPC relate to myocardial contractile function.

Methods and results

Rats were subjected to different durations of left anterior descending artery (LAD) occlusion, with or without preceding IPC. Echocardiograms were acquired to assess cardiac contraction in the affected myocardial segment. Infarction size was evaluated using triphenyl tetrazolium chloride staining. Phosphoproteomic analysis was performed in heart tissue from preconditioned and non-preconditioned animals. In contrast to rats without IPC, reversible akinesia was observed in a majority of the rats that were subjected to IPC and subsequently exposed to ischemia of 13.5 or 15 min of ischemia. Phosphoproteomic analysis revealed significant differential regulation of 786 phosphopeptides between IPC and non-IPC groups, with significant associations with the sarcomere, Z-disc, and actin binding.

Conclusion

IPC induces changes in phosphosites of proteins involved in myocardial contraction; and both accentuates post-ischemic myocardial stunning and reduces infarct size.
Study on the mechanical characteristics of sand pebble surrounding rock considering the disturbance effect of tunnel excavation
Authors: Huang Maozhou , Yu Daidai , Li Xin , Zhao Yinting
Published: March 2024

When conducting tunnel construction in sandy gravel strata, disturbance to the sandy gravel soil is inevitable, resulting in alterations to the properties of the surrounding rock. This paper investigates the relationship between the relative density (Dr) and shear strength parameters under different disturbance states through the implementation of indoor triaxial tests. Utilizing Dr as a disturbance parameter, a unified disturbance function that reflects the weakening and strengthening of sandy gravel soil is proposed. Furthermore, a revised constitutive model based on this unified disturbance function is established for the first time. The study results indicated that the results calculated by traditional models, which do not take into account disturbance effects, deviate from the experimental results by more than 20%. However, the error rate of the results computed by the modified model can be reduced to within 8%. The new model establishes a dynamic relationship between relative compactness and shear strength parameters of sand and pebble soils, which can take into account both the effects of negative and positive perturbations. The results can more accurately characterise the strength and deformation properties of the surrounding rock under the influence of construction disturbances in sand and pebble ground tunnels.
U-shaped relationship between fasting blood glucose and urinary albumin-to-creatinine ratio in the general United States population
Authors: Song Jianling , Wang Ping , Li Hong
Published: March 2024

Objective

The current controversy surrounding the association between fasting blood glucose (FBG) and albuminuria necessitates further investigation. Hence, the primary objective of this study was to examine the relationship between FBG and urinary albumin-to-creatinine ratio (UACR).

Methods

A cohort of complete data from National Health and Nutrition Examination Survey (NHANES) participants (1999-2020) was analyzed. Linear regression analyses and a generalized additive model explored the association between FBG and UACR. Furthermore, the stability of this relationship across different populations was assessed.

Results

The study involved a total of 20,264 participants who were identified as U.S. citizens. By employing linear regression analysis, a statistically significant relationship was observed between elevated FBG levels and an increase in UACR (P<0.0001). Additionally, using a generalized additive model analysis, a U-shaped correlation between FBG and UACR was identified. Further examination using threshold effect analysis indicated a turning point for FBG at 5.44 mmol/L. A noteworthy finding in multiple populations is the consistent U-shaped association between FBG and UACR, except for individuals with serum uric acid levels ≥420 μmol/L and those who refrain from alcohol consumption.

Conclusion

The general U.S. population has a U-shaped nonlinear relationship between FBG and UACR.
The relationship between weight-adjusted-waist index and diabetic kidney disease in patients with type 2 diabetes mellitus
Authors: Wang Zhaoxiang , Shao Xuejing , Xu Wei , Xue Bingshuang , Zhong Shao , Yang Qichao
Published: March 2024

Purpose

Obesity, particularly abdominal obesity, is seen as a risk factor for diabetic complications. The weight-adjusted-waist index (WWI) is a recently developed index for measuring adiposity. Our goal was to uncover the potential correlation between the WWI index and diabetic kidney disease (DKD) risk.

Methods

This cross-sectional study included adults with type 2 diabetes mellitus (T2DM) who participated in the NHANES database (2007-2018). The WWI index was calculated as waist circumference (WC, cm) divided by the square root of weight (kg). DKD was diagnosed based on impaired estimated glomerular filtration rate (eGFR<60 mL/min/1.73m2), albuminuria (urinary albumin to urinary creatinine ratio>30 mg/g), or both in T2DM patients. The independent relationship between WWI index and DKD risk was evaluated.

Results

A total of 5,028 participants with T2DM were included, with an average WWI index of 11.61 ± 0.02. As the quartile range of the WWI index increased, the prevalence of DKD gradually increased (26.76% vs. 32.63% vs. 39.06% vs. 42.96%, P<0.001). After adjusting for various confounding factors, the WWI index was independently associated with DKD risk (OR=1.32, 95%CI:1.12-1.56, P<0.001). The area under the ROC curve (AUC) of the WWI index was higher than that of body mass index (BMI, kg/m2) and WC. Subgroup analysis suggested that the relationship between the WWI index and DKD risk was of greater concern in patients over 60 years old and those with cardiovascular disease.

Conclusions

Our findings suggest that higher WWI levels are linked to DKD in T2DM patients. The WWI index could be a cost-effective and simple way to detect DKD, but further prospective studies are needed to confirm this.
Emerging attributes of adaptive governance in the global south
Authors: Akther Shahana , Evans James
Published: March 2024

Adaptive governance is widely considered an effective approach to address the complexities and uncertainties of socio-ecological systems. The application of adaptive governance to sustainable environmental governance in the global south has not been sufficiently explored. There is a gap in the literature in the global south, especially given its conceptual roots in the global north. A number of reviews identified some key conceptual and practical gaps related to adaptive governance principles and the challenges to implementing them. To address this gap, this paper presents a systematic literature review of adaptive governance scholarship focused on the global south published between 2003 and 2022. The review discusses adaptive governance’s key principles and framings, as well as the challenges of implementing it in the global south. This paper examines the factors that influence the emergence of adaptive governance and how this framing has been used to understand effective environmental governance within the global south’s diverse socio-political and institutional settings. The review specifically focuses on Africa and South Asia, which are densely populated with limited financial and institutional capacity. Sustainable environmental governance is crucial in these regions not only for the wellbeing of the population, but also for the health of the planet. A review of adaptive governance scholarship identified emerging attributes that improve government structures and processes, as well as proposed attributes that would minimize challenges and improve adaptive capacity. The key emerging attributes are formal and informal networks, social learning, community engagement and proposed attributes are flexible, integrated and participatory institutional governance, inclusive decision making, context-specific strategies, accountability, and capacity development. These attributes provide a framework for adaptive governance scholarship for examining different governance structures and processes in different socio-ecological systems. This paper concludes with a framework for future research that can facilitate adaptive governance in the context of sustainable environmental management in the global south.
Evaluation of ecological carrying capacity and construction of ecological security pattern in West Liaohe River Basin of China
Authors: Zheng Ying , Tang Pengcheng , Dong Lei , Yao Zhenyu , Guo Jianying
Published: March 2024

The West Liaohe River Basin (WRLB) is a typical agro-pastoral interlaced zone in Northeast China where excessive economic development activities brought great pressure on the ecosystem and caused a series of ecological problems, having a negative effect on regional ecological carrying capacity (ECC). The rational construction of ecological security pattern (ESP) is an effective way to improve regional ECC and alleviate the contradiction between ecological protection and economic development. In this study, taking the WLRB as an example, spatiotemporal changes of ECC in the WLRB from 2000 to 2020 were explored by using spatial principal component analysis (SPCA). Furthermore, ecological sources were determined by coupling ECC evaluation results with important ecological patches such as natural protected areas, and the minimum cumulative resistance (MCR) model combined with the circuit theory method were employed to identify ecological security zoning, ecological corridors and key ecological nodes. Then a comprehensive ESP of the basin was constructed. The results show as follows: 1) The ECC of the overall WLRB was at medium carrying level, yet was spatially differentiated, which decreased from the periphery to the center of the basin in general. ECC showed a fluctuating upward trend from 2000 to 2020. 2) The ecological source area of the WLRB was 21926.91 km², accounting for 17.33% of the total study area. The ecological sources were seriously fragmentated and mainly distributed in the mountain area. The area of ecological conservation zone, optimized buffer zone, ecological transition zone, ecological prevention and control zone were 55672.69 km², 32662.24 km², 23862.84 km² and 12021.04 km², accounting for 44.82%, 26.29%, 19.21% and 9.68%, respectively. We also extracted 95 ecological corridors (with a total length of 3130.97 km), 49 ecological pinch points (with a total area of 200.33 km²) and 30 ecological barrier points (with a total area of 318.30 km²), constituting a “points-lines-planes” comprehensive ecological security pattern. This research can provide scientific reference for the protection and restoration of ecological environment and regional sustainable development.
Impact of deep phenotyping: high diagnostic yield in a diverse pediatric population of 172 patients through clinical whole-genome sequencing at a single center
Authors: Akgun-Dogan Ozlem , Tuc Bengur Ecenur , Ay Beril , Ozkose Gulsah Sebnem , Kar Emre , Bengur Fuat Baris , Bulut Aybike S. , Yigit Ayca , Aydin Eylul , Esen Fatma Nisa , Ozdemir Ozkan , Yesilyurt Ahmet , Alanay Yasemin
Published: March 2024

Background: Pediatric patients with undiagnosed conditions, particularly those suspected of having Mendelian genetic disorders, pose a significant challenge in healthcare. This study investigates the diagnostic yield of whole-genome sequencing (WGS) in a pediatric cohort with diverse phenotypes, particularly focusing on the role of clinical expertise in interpreting WGS results.

Methods: A retrospective cohort study was conducted at Acibadem University’s Maslak Hospital in Istanbul, Turkey, involving pediatric patients (0–18 years) who underwent diagnostic WGS testing. Clinical assessments, family histories, and previous laboratory and imaging studies were analyzed. Variants were classified and interpreted in conjunction with clinical findings.

Results: The cohort comprised 172 pediatric patients, aged 0–5 years (62.8%). International patients (28.5%) were from 20 different countries. WGS was used as a first-tier approach in 61.6% of patients. The diagnostic yield of WGS reached 61.0%, enhanced by reclassification of variants of uncertain significance (VUS) through reverse phenotyping by an experienced clinical geneticist. Consanguinity was 18.6% of the overall cohort. Dual diagnoses were carried out for 8.5% of solved patients.

Discussion: Our study particularly advocates for the selection of WGS as a first-tier testing approach in infants and children with rare diseases, who were under 5 years of age, thereby potentially shortening the duration of the diagnostic odyssey. The results also emphasize the critical role of a single clinical geneticist’s expertise in deep phenotyping and reverse phenotyping, which contributed significantly to the high diagnostic yield.
Race, ethnicity, ancestry, and aspects that impact HLA data and matching for transplant
Authors: Madbouly Abeer , Bolon Yung-Tsi
Published: March 2024

Race, ethnicity, and ancestry are terms that are often misinterpreted and/or used interchangeably. There is lack of consensus in the scientific literature on the definition of these terms and insufficient guidelines on the proper classification, collection, and application of this data in the scientific community. However, defining groups for human populations is crucial for multiple healthcare applications and clinical research. Some examples impacted by population classification include HLA matching for stem-cell or solid organ transplant, identifying disease associations and/or adverse drug reactions, defining social determinants of health, understanding diverse representation in research studies, and identifying potential biases. This article describes aspects of race, ethnicity and ancestry information that impact the stem-cell or solid organ transplantation field with particular focus on HLA data collected from donors and recipients by donor registries or transplant centers.
Patterns of inter-state irregular migration in Africa: insights from Ethiopian migrants to the Republic of South Africa
Authors: Megersa Hailu , Tafesse Tesfaye
Published: March 2024

Recent research suggests a significant rise in both international and intra-African migrations, with South Africa emerging as the primary destination for irregular migrants in the region. However, the phenomenon of irregular migration to South Africa has received limited attention despite the growing number of migrants hosted by the country. To address this gap, this study adopts a concurrent cross-sectional mixed-methods approach to explore the patterns of inter-state irregular migration in Africa, specifically focusing on Ethiopian migrants to the Republic of South Africa (RSA). The investigation draws on quantitative data collected from 316 migrant returnees, as well as qualitative in-depth interviews and focus-group discussions. The findings of this study reveal that there is a decline in the patterns of Ethiopian irregular migration to the RSA within the past decade due to tight legal restrictions. The COVID-19 pandemic has had a significant impact on the pattern of irregular migration, leading to a decline in the number of migrants from mid-2018 to 2020 due to stringent border closures. Irregular migration to the RSA tends to be temporary, with an increasing migrants returning to their home country once they have achieved economic success or as they encountered precarious conditions at the destination. Addressing the root causes that drive migration, improving border control mechanisms, and implementing inclusive integration strategies are key steps toward minimizing the risks and maximizing the benefits associated with this migration phenomenon.
Causal role of immune cells in psoriasis: a Mendelian randomization analysis
Authors: Wang Anning , Zhang Jingyuan
Published: March 2024

Background

A growing body of evidence has shown that immune cells are linked to psoriasis. It is, however, still unclear if these associations reflect a relationship of cause and effect.

Objective

We employed a two-sample Mendelian randomization (MR)-based study to elucidate the probable causative connection between immune cells and psoriasis.

Methods

Summary information for psoriasis (Ncase = 5,427, Ncontrol = 479,171) was obtained from the European Bioinformatics Institute. Summarized statistical information on 731 immune cell features, including morphological parameters (MP; n = 32), relative cell number (n = 192), median fluorescence intensity (MFI) of surface antigens (n = 389), and absolute cell number (n = 118), was obtained from the genome-wide association studies (GWAS) catalog. The research consisted of forward MR analysis, in which immune cell traits were used as the exposure factor, and psoriasis was the outcome, as well as reverse MR analysis, in which psoriasis was used as the exposure factor, and immune cell traits were the outcome. We ran numerous sensitivity analyses to ascertain the study results for robustness, heterogeneity, and potential multiple-biological effects.

Result

This research determined a probable causative connection between immune cells and psoriasis. In particular, we identified 36 distinct types of immune cells that are potentially causally linked to psoriasis.

Conclusion

Our findings indicate strong causal correlations between 36 immunological phenotypes and psoriasis, thus, directing future clinical trials.
Targeting the gut microbiota to enhance the antitumor efficacy and attenuate the toxicity of CAR-T cell therapy: a new hope?
Authors: Zhang Peng-Fei , Xie Dan
Published: March 2024

Chimeric antigen receptor (CAR) -T cell therapy has achieved tremendous efficacy in the treatment of hematologic malignancies and represents a promising treatment regimen for cancer. Despite the striking response in patients with hematologic malignancies, most patients with solid tumors treated with CAR-T cells have a low response rate and experience major adverse effects, which indicates the need for biomarkers that can predict and improve clinical outcomes with future CAR-T cell treatments. Recently, the role of the gut microbiota in cancer therapy has been established, and growing evidence has suggested that gut microbiota signatures may be harnessed to personally predict therapeutic response or adverse effects in optimizing CAR-T cell therapy. In this review, we discuss current understanding of CAR-T cell therapy and the gut microbiota, and the interplay between the gut microbiota and CAR-T cell therapy. Above all, we highlight potential strategies and challenges in harnessing the gut microbiota as a predictor and modifier of CAR-T cell therapy efficacy while attenuating toxicity.
ARDS and aging: TYMS emerges as a promising biomarker and therapeutic target
Authors: Li Gang , Yan Ke , Zhang Wanyi , Pan Haiyan , Guo Pengxiang
Published: March 2024

Background

Acute Respiratory Distress Syndrome (ARDS) is a common condition in the intensive care unit (ICU) with a high mortality rate, yet the diagnosis rate remains low. Recent studies have increasingly highlighted the role of aging in the occurrence and progression of ARDS. This study is committed to investigating the pathogenic mechanisms of cellular and genetic changes in elderly ARDS patients, providing theoretical support for the precise treatment of ARDS.

Methods

Gene expression profiles for control and ARDS samples were obtained from the Gene Expression Omnibus (GEO) database, while aging-related genes (ARGs) were sourced from the Human Aging Genomic Resources (HAGR) database. Differentially expressed genes (DEGs) were subjected to functional enrichment analysis to understand their roles in ARDS and aging. The Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning pinpointed key modules and marker genes, with ROC curves illustrating their significance. The expression of four ARDS-ARDEGs was validated in lung samples from aged mice with ARDS using qRT-PCR. Gene set enrichment analysis (GSEA) investigated the signaling pathways and immune cell infiltration associated with TYMS expression. Single-nucleus RNA sequencing (snRNA-Seq) explored gene-level differences among cells to investigate intercellular communication during ARDS onset and progression.

Results

ARDEGs are involved in cellular responses to DNA damage stimuli, inflammatory reactions, and cellular senescence pathways. The MEmagenta module exhibited a significant correlation with elderly ARDS patients. The LASSO, RRF, and XGBoost algorithms were employed to screen for signature genes, including CKAP2, P2RY14, RBP2, and TYMS. Further validation emphasized the potential role of TYMS in the onset and progression of ARDS. Immune cell infiltration indicated differential proportion and correlations with TYMS expression. SnRNA-Seq and cell-cell communication analysis revealed that TYMS is highly expressed in endothelial cells, and the SEMA3 signaling pathway primarily mediates cell communication between endothelial cells and other cells.

Conclusion

Endothelial cell damage associated with aging could contribute to ARDS progression by triggering inflammation. TYMS emerges as a promising diagnostic biomarker and potential therapeutic target for ARDS.
GD2-targeting therapy: a comparative analysis of approaches and promising directions
Authors: Philippova Julia , Shevchenko Julia , Sennikov Sergey
Published: March 2024

Disialoganglioside GD2 is a promising target for immunotherapy with expression primarily restricted to neuroectodermal and epithelial tumor cells. Although its role in the maintenance and repair of neural tissue is well-established, its functions during normal organism development remain understudied. Meanwhile, studies have shown that GD2 plays an important role in tumorigenesis. Its functions include proliferation, invasion, motility, and metastasis, and its high expression and ability to transform the tumor microenvironment may be associated with a malignant phenotype. Structurally, GD2 is a glycosphingolipid that is stably expressed on the surface of tumor cells, making it a suitable candidate for targeting by antibodies or chimeric antigen receptors. Based on mouse monoclonal antibodies, chimeric and humanized antibodies and their combinations with cytokines, toxins, drugs, radionuclides, nanoparticles as well as chimeric antigen receptor have been developed. Furthermore, vaccines and photoimmunotherapy are being used to treat GD2-positive tumors, and GD2 aptamers can be used for targeting. In the field of cell therapy, allogeneic immunocompetent cells are also being utilized to enhance GD2 therapy. Efforts are currently being made to optimize the chimeric antigen receptor by modifying its design or by transducing not only αβ T cells, but also γδ T cells, NK cells, NKT cells, and macrophages. In addition, immunotherapy can combine both diagnostic and therapeutic methods, allowing for early detection of disease and minimal residual disease. This review discusses each immunotherapy method and strategy, its advantages and disadvantages, and highlights future directions for GD2 therapy.
Btbd8 deficiency reduces susceptibility to colitis by enhancing intestinal barrier function and suppressing inflammation
Authors: Yang Xiaoqiong , He Zichan , Dong Qiman , Nai Shanshan , Duan Xiaowei , Yu Jiayu , Zhao Nannan , Du Xiaoling , Chen Lingyi
Published: March 2024

Introduction

BTBD8 has been identified as a susceptible gene for inflammatory bowel diseases (IBD). However, the function of BTBD8 in normal development and IBD pathogenesis remains unknown.

Methods

We administered drinking water with 3% dextran sodium sulfate (DSS) to wild-type (WT) and Btbd8 knockout (KO) mice for seven consecutive days to induce IBD. Subsequently, we further examined whether Btbd8 KO affects intestinal barrier and inflammation.

Results

We demonstrated that Btbd8 deficiency partially protects mice from DSS-induced IBD, even though no obvious phenotypes were observed in Btbd8 KO mice. Btbd8 deletion leads to strengthened tight junctions between intestinal epithelial cells, elevated intestinal stem cell activity, and enhanced mucus layer. All these three mechanisms work together to improve the intestinal barrier integrity in Btbd8 KO mice. In addition, Btbd8 deficiency mitigates inflammation by reducing the expression of IL-1β and IL-6 by macrophages.

Discussion

Our studies validate the crucial role of Btbd8 in IBD pathogenesis, and reveal that Btbd8 deficiency may ameliorate DSS-induced IBD through improving the intestinal barrier integrity, as well as suppressing inflammatory response mediated by macrophages. These findings suggest that Btbd8 could be a promising therapeutic target for the treatment of IBD.
Programmable flow injection: a versatile technique for benchtop and autonomous analysis of phosphate and silicate in seawater
Authors: Lebrec Marine , Grand Maxime M.
Published: March 2024

High-resolution, autonomous monitoring of phosphate and silicate in the marine environment is essential to understand their complex dynamics and implications for the functioning of marine ecosystems. In the absence of dependable reagent-less sensors for these nutrients, leveraging established colorimetric techniques using miniaturized analyzers, such as programmable Flow Injection (pFI), offers the best immediate solution to meet oceanographic accuracy and precision standards. In this work, we further optimize the phosphomolybdate and silicomolybdate assays recently adapted for use with pFI, laying the groundwork for the technique’s use for long-term, autonomous operations. For both assays, we show that only a narrow range of acidities and molybdate concentrations can maximize sensitivity while minimizing salt effects. In addition, we demonstrate the stability of our optimized colorimetric reagent formulations, ensuring that analytical sensitivity remains within 10% of initial levels for at least 35 days of continuous use. We then applied our optimized protocols to produce oceanographically consistent phosphate and silicate profiles at the Hawaii Ocean Time Series (HOTS) and Southern Ocean Time Series (SOTS), respectively, which compared favorably against a reference method and historical data. Using certified reference materials for nutrients in seawater, we show that our pFI protocols, optimized for long-term operations, achieve a shipboard precision better than 6% and a relative combined uncertainty (k=1) of 4.5% for phosphate (0.45 - 2.95 µmol L-1) and 6.2% for silicate (2.2 to 103 µmol L-1). To demonstrate pFI’s potential as a versatile tool for autonomous monitoring, we report a five-day hourly phosphate time series at a coastal shore station in central California (n=121 analyses), examine phosphate uptake by seaweed at five-minute intervals at a seaweed aquaculture facility (n=103), and discuss a unique, high-resolution surface silicate transect spanning multiple frontal zones in the Australian sector of the Southern Ocean (n=249). These data, obtained using a commercially available pFI analyzer, confirm that pFI is a viable technology for autonomous monitoring of phosphate and silicate, paving the way for more ambitious, long-term deployments in a variety of settings.
Unraveling the chemical identification and biological potential of the genus Asparagopsis: a comprehensive review
Authors: Cheong Kit-Leong , Li Guanghui , Wang Min , Yang Yufeng , Zhong Saiyi
Published: March 2024

The genus Asparagopsis has garnered escalating attention in the spheres of marine biology and biotechnology due to its diverse chemical composition and promising biological capabilities. This all-encompassing review is dedicated to conducting an exhaustive inquiry into the chemical identification and biological importance of Asparagopsis species. By meticulously dissecting the array of chemical compounds found in genus Asparagopsis, encompassing polysaccharides, lipids, proteins, sterols, and bromoform. We unveil their potential utility in realms such as biomedicine, biotechnology, and the conservation of the environment. Furthermore, we delve into the bioactive attributes inherent in these compounds, encompassing effects such as antioxidative, antimicrobial, and anti-inflammatory properties, as well as their conceivable role in cancer treatments. Furthermore, this review underscores the environmental pertinence of genus Asparagopsis, particularly its capacity to mitigate climate change through the generation of compounds that alleviate greenhouse gas effects. Additionally, we delve into the economic facets of this genus, spanning from its integration into food additives to its contributions in cosmetics and sustainable agriculture. This comprehensive review furnishes a multi-faceted comprehension of Asparagopsis, illuminating its chemical diversity and biological significance, thereby paving the way for further explorations into its potential contributions across a spectrum of sectors.
Influence of incubation period on membrane patch color for insoluble contaminant measurement in degraded hydraulic oils
Authors: Pravda Stepan , Sedenka David , Blata Jan , Hrabovsky Leopold
Published: March 2024

Insoluble contaminants and varnish, resulting from oil degradation byproducts and sometimes depleted additive molecules, are initiated primarily due to thermal stress on the oil. This poses significant challenges in tribology, particularly for the lubrication systems of modern complex machinery, leading to severe debilitating effects such as loss of operating clearances and impaired heat transfer. Addressing varnish buildup is crucial, and timely oil analysis emerges as a valuable tool, offering essential insights into the oil degradation level and the potential presence of insoluble contaminants. Among the various laboratory testing methods available to assess varnish potential, colorimetric analysis, specifically Membrane Patch Colorimetry (MPC), is widely applied owing to its efficiency and cost-effectiveness. This study extends the application of MPC test principles, commonly utilized for turbine oils, to measure insoluble contaminants generated by degraded hydraulic fluids. Adhering to the ASTM D7843-21 standard, which stipulates the precision of this testing method for turbine oils is contingent upon the sample’s incubation period, our investigation focuses on exploring modifications to the standard 72-hour incubation period. We aim to assess the viability of shortening or extending this duration for conducting MPC tests on used hydraulic fluids, thereby potentially enhancing the precision and relevance of MPC tests in hydraulic fluid analysis.
Nano-radiopharmaceuticals as therapeutic agents
Authors: Dixit Tanu , Dave Nayomi , Basu Kausani , Sonawane Pranav , Gawas Trutuja , Ravindran Selvan
Published: March 2024

In recent years, there has been an increased interest in exploring the potential synergy between nanotechnology and nuclear medicine. The application of radioactive isotopes, commonly referred to as radiopharmaceuticals, is recognized in nuclear medicine for diagnosing and treating various diseases. Unlike conventional pharmaceutical agents, radiopharmaceuticals are designed to work without any pharmacological impact on the body. Nevertheless, the radiation dosage employed in radiopharmaceuticals is often sufficiently high to elicit adverse effects associated with radiation exposure. Exploiting their capacity for selective accumulation on specific organ targets, radiopharmaceuticals have utility in treating diverse disorders. The incorporation of nanosystems may additionally augment the targeting capability of radiopharmaceuticals, leveraging their distinct pharmacokinetic characteristics. Conversely, radionuclides could be used in research to assess nanosystems pharmacologically. However, more investigation is needed to verify the safety and effectiveness of radiopharmaceutical applications mediated by nanosystems. The use of nano-radiopharmaceuticals as therapeutic agents to treat various illnesses and disorders is majorly covered in this review. The targeted approach to cancer therapy and various types of nanotools for nano-radiopharmaceutical delivery, is also covered in this article.
Single cell analysis of short-term dry eye induced changes in cornea immune cell populations
Authors: Alam Jehan , Yaman Ebru , Silva Gerda Cristal Villalba , Chen Rui , de Paiva Cintia S. , Stepp Mary Ann , Pflugfelder Stephen C.
Published: March 2024

Background

Dry eye causes corneal inflammation, epitheliopathy and sensorineural changes. This study evaluates the hypothesis that dry eye alters the percentages and transcriptional profiles of immune cell populations in the cornea.

Methods

Desiccating stress (DS) induced dry eye was created by pharmacologic suppression of tear secretion and exposure to drafty low humidity environment. Expression profiling of corneal immune cells was performed by single-cell RNA sequencing (scRNA-seq). Cell differentiation trajectories and cell fate were modeled through RNA velocity analysis. Confocal microscopy was used to immunodetect corneal immune cells. Irritation response to topical neurostimulants was assessed.

Results

Twelve corneal immune cell populations based on their transcriptional profiles were identified at baseline and consist of monocytes, resident (rMP) and MMP12/13 high macrophages, dendritic cells (cDC2), neutrophils, mast cells, pre T/B cells, and innate (γDT, ILC2, NK) and conventional T and B lymphocytes. T cells and resident macrophages (rMP) were the largest populations in the normal cornea comprising 18.6 and 18.2 percent, respectively. rMP increased to 55.2% of cells after 5 days of DS. Significant changes in expression of 1,365 genes (adj p < 0.0001) were noted in rMP with increases in cytokines and chemokines (Tnf, Cxcl1, Ccl12, Il1rn), inflammatory markers (Vcam, Adam17, Junb), the TAM receptor (Mertk), and decreases in complement and MHCII genes. A differentiation trajectory from monocytes to terminal state rMP was found. Phagocytosis, C-type lectin receptor signaling, NF-kappa B signaling and Toll-like receptor signaling were among the pathways with enhanced activity in these cells. The percentage of MRC1+ rMPs increased in the cornea and they were observed in the basal epithelium adjacent to epithelial nerve plexus. Concentration of the chemokine CXCL1 increased in the cornea and it heightened irritation/pain responses to topically applied hypertonic saline.

Conclusion

These findings indicate that DS recruits monocytes that differentiate to macrophages with increased expression of inflammation associated genes. The proximity of these macrophages to cornea nerves and their expression of neurosensitizers suggests they contribute to the corneal sensorineural changes in dry eye.
Morphological and phylogenetic analyses reveal two new Penicillium species isolated from the ancient Great Wall loess in Beijing, China
Authors: Liang Ruina , Yang Qiqi , Li Ying , Yin Guohua , Zhao Guozhu
Published: March 2024

Introduction

Penicillium species exhibit a broad distribution in nature and play a crucial role in human and ecological environments.

Methods

Two Penicillium species isolated from the ancient Great Wall loess in the Mentougou District of Beijing, China, were identified and described as new species, namely, Penicillium acidogenicum and P. floccosum, based on morphological characteristics and phylogenetic analyses of multiple genes including ITS, BenA, CaM, and RPB2 genes.

Results

Phylogenetic analyses showed that both novel species formed a distinctive lineage and that they were most closely related to P. chrzaszczii and P. osmophilum, respectively.

Discussion

Penicillium acidogenicum is characterized by biverticillate conidiophores that produce globose conidia and is distinguished from similar species by its capacity to grow on CYA at 30°C. Penicillium floccosum is typically recognized by its restricted growth and floccose colony texture. The description of these two new species provided additional knowledge and new insights into the ecology and distribution of Penicillium.