bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic drivers of human plasma metabolites that determine mortality in heart failure patients with reduced ejection fraction
Authors: Revathi Venkateswaran Vandana , She Ruicong , Gui Hongsheng , Luzum Jasmine A. , Bryson Timothy D. , Malouf Zack E. , Williams L. Keoki , Sabbah Hani N. , Gardell Stephen J. , Lanfear David E.
Published: July 2024

Background

Heart failure with reduced ejection fraction (HFrEF) remains a significant public health issue, with the disease advancing despite neurohormonal antagonism. Energetic dysfunction is a likely contributor to residual disease progression, and we have previously reported a strong association of plasma metabolite profiles with survival among patients with HFrEF. However, the genetic and biologic mechanisms that underlie the metabolite-survival association in HFrEF were uncertain.

Methods and results

We performed genetic mapping of the key metabolite parameters, followed by mediation analyses of metabolites and genotypes on survival, and genetic pathway analyses. Patients with HFrEF (n = 1,003) in the Henry Ford Pharmacogenomic Registry (HFPGR; 500 self-reported Black/African race patients [AA], 503 self-reported White/European race patients [EA], and 249 deaths over a median of 2.7 years) with genome-wide genotyping and targeted metabolomic profiling of plasma were included. We tested genome-wide association (GWA) of single nucleotide polymorphisms (SNPs) with the prognostic metabolite profile (PMP) and its components; first stratified by race, and then combined via meta-analysis for the entire cohort. Seven independent loci were identified as GWA significant hits in AA patients (3 for PMP and 4 for individual metabolites), one of which was also significant in the entire cohort (rs944469). No genome wide significant hits were found in White/EA patients. Among these SNPs, only rs35792152, (a hit for 3.HBA) tended to be associated with mortality in standard survival analysis (HR = 1.436, p = 0.052). The mediation analyses indicated several significant associations between SNPs, metabolites, and mortality in AA patients. Functional annotation mapping (FUMA) implicated inflammation, DNA metabolic, and mRNA splicing processes.

Conclusions

GWAS of key metabolites and survival along with FUMA pathway analysis revealed new candidate genes which unveiled molecular pathways that contribute to HF disease progression via metabolic and energetic abnormalities.
An alternative approach for the sediment control of in-channel stony debris flows with an application to the case study of Ru Secco Creek (Venetian Dolomites, Northeast Italy)
Authors: Barbini Matteo , Bernard Martino , Boreggio Mauro , Schiavo Massimiliano , D’Agostino Vincenzo , Gregoretti Carlo
Published: July 2024

Controlling sediment to reduce debris-flow hazard is generally approached using retention basins that can be closed or have an outlet structure, generally an open check dam. They are usually placed in mild slope zones that allow minimal works for the excavation and the foundation of the outlet structure if present. Recently, it has been shown that the detention of sediments can also be achieved in the high-sloping reaches of debris-flow channels using deposition areas, basins that are open on the downstream side. In this work, we propose an approach for controlling the sediment volume transported by debris flows consisting of a cascade of deposition areas and retention basins. We also include a framework for planning, sizing, and checking the works. Two scenarios are considered, corresponding to the maximum values of the debris-flow peak discharge and volume, respectively. Moreover, the presence or absence of boulders is also considered. For this purpose, a method that evaluates the clogging of a single open check dam as a function of the coarse fraction of the sediment volume is simply extended to the case of multiple dams and implemented in a routing model. The proposed approach is applied along Ru Secco Creek in northeast Italy to defend a resort area and a village hit by a high-magnitude debris flow in 2015. After a careful survey and study, a solution with a combination of deposition areas and retention basins is planned and sized. The validity and performance of the proposed solution are analyzed using debris-flow modeling for two scenarios, considering both the absence and presence of boulders. Most of the sediment volume transported by debris flows is trapped, and a small solid discharge flows downstream of the works.
The velocity extraction and feature analysis of glacier surface motion in the Gongar region based on multi-source remote sensing data
Authors: Gu Fang , Zhang Sicong , Zhang Qinqin , Li Dan , Fu Yingzi , Chen Xuehua
Published: July 2024

The movement of glaciers plays a crucial role in environmental and geological processes, significantly influencing the formation and dynamics of ice bodies. This study leverages feature tracking technology to analyze optical and Synthetic Aperture Radar (SAR) remote sensing imagery, specifically GF-1 optical images and GF-3, Sentinel-1 SAR images, captured during the 2020 to 2021 ablation season in Gongar. The aim was to quantify glacier surface velocities and to evaluate the comparative effectiveness of different remote sensing modalities in capturing these dynamics. Our findings indicate a strong consistency in the spatial distribution of glacier surface velocities derived from diverse remote sensing data sources, with high-precision optical imagery (GF-1) yielding the most accurate velocity measurements, followed by Sentinel-1 SAR data. Notably, large glaciers in Gongar exhibited rapid movements, with an average velocity of 0.16 m/d, primarily at elevations between 4,500 and 6,500 m. The fastest velocities were recorded at approximately 4,500 m elevation. Glaciers with inclines ranging from 10° to 60° displayed the highest velocities within the 20°–30° slope range. It was observed that glaciers on the southeast slope moved faster, exhibiting the highest average surface velocity, in contrast to those on the west slope, which moved more slowly. The surface velocity of the ice tongue region of Krayaylak Glacier that the largest glacier in Pamir, was observed to be lower than 0.6 m/d, indicating a slow movement speed. The study also reveals that the effectiveness of different remote sensing data in detecting glacier velocity in Gongar, with high-resolution data more accurately capturing surface velocities in melting areas or those with slower movement. This study underscores the importance of multi-source remote sensing data in understanding glacier dynamics and contributes valuable insights into the mechanisms driving glacier movements.
Identifying mathematics teachers’ competency to look at elementary mathematics from an advanced standpoint: a pilot study
Authors: Cheng Hiu Fai Kell , Leung King Shun , Leung Kui Chiu Issic , Ma Chun Hung , Man Yiu Kwong , Ng Tsz Kit Davy , Yuen Manwai
Published: July 2024

This study evaluates the impact of “the ability to look at elementary mathematics from an advanced standpoint (EMFAS),” which was originally proposed by Felix Klein, in mathematics education. By strengthening the connection between elementary and tertiary mathematics, mathematics teachers are expected to have advanced knowledge to offer students higher mathematical insights. Thus, EMFAS serves as a great indicator for measuring teaching effectiveness. By investigating newly qualified and pre-service teachers’ ability to apply EMFAS techniques, we analyze the logic involved in solving some specially constructed problems and how teachers could deliver mathematical knowledge to students at the elementary level with the advanced knowledge they possess. We explain the importance of the EMFAS course, in terms of pedagogy and content knowledge. This course prepares pre-service mathematics teachers by equipping them with advanced knowledge for their future profession. This study evaluates mathematics teachers’ proficiency in applying EMFAS techniques via a problem set and interviews. We summarize the hierarchical nature of how teachers perceive EMFAS, which could play an important role in guiding pedagogy in mathematics education.
Association between blood lead levels and parathyroid hormone among United States adolescents aged 12–19: a cross-sectional study
Authors: He Baomei , Wang Xiaowei , Luo Huanjun , Zhou Qin
Published: July 2024

Aims

Studies on the association between serum lead levels and parathyroid function in adolescents are lacking. Therefore, in this study, we elucidated the possible association between blood lead levels (BLLs) and the parathyroid hormone (PTH) in adolescents aged 12–19 years in the United States.

Methods

In this study, information from the database of the National Health and Nutrition Examination Survey was utilized. The study included 3919 participants from survey cycles between 2003–2004 and 2005–2006. Multivariable linear regression analysis was performed to determine the correlation between BLLs and PTH. Furthermore, smooth curve fitting was utilized to analyze the dose–response relationship between BLLs and PTH.

Results

Multivariable linear regression analysis revealed that every 1 μg/dL increase in BLLs was associated with 0.67 pg/mL increase in PTH (β = 0.67, 95% CI: 0.16–1.18, p < 0.01). However, sex-stratified subgroup analysis revealed that this positive association was only observed in males (β = 1.16, 95% CI: 0.50–1.83 p < 0.01). Smooth curve fitting revealed a positive correlation between BLLs and PTH.

Conclusions

In adolescents in the United States, BLLs are positively correlated with PTH, particularly in males.
Childhood obesity from the genes to the epigenome
Authors: Sivakumar Senthil , Lama Dechen , Rabhi Nabil
Published: July 2024

The prevalence of obesity and its associated comorbidities has surged dramatically in recent decades. Especially concerning is the increased rate of childhood obesity, resulting in diseases traditionally associated only with adulthood. While obesity fundamentally arises from energy imbalance, emerging evidence over the past decade has revealed the involvement of additional factors. Epidemiological and murine studies have provided extensive evidence linking parental obesity to increased offspring weight and subsequent cardiometabolic complications in adulthood. Offspring exposed to an obese environment during conception, pregnancy, and/or lactation often exhibit increased body weight and long-term metabolic health issues, suggesting a transgenerational inheritance of disease susceptibility through epigenetic mechanisms rather than solely classic genetic mutations. In this review, we explore the current understanding of the mechanisms mediating transgenerational and intergenerational transmission of obesity. We delve into recent findings regarding both paternal and maternal obesity, shedding light on the underlying mechanisms and potential sex differences in offspring outcomes. A deeper understanding of the mechanisms behind obesity inheritance holds promise for enhancing clinical management strategies in offspring and breaking the cycle of increased metabolic risk across generations.
Observational and genetic association of non-alcoholic fatty liver disease and calcific aortic valve disease
Authors: Hao Qing-Yun , Zeng Yu-Hong , Lin Ying , Guo Jing-Bin , Li Shi-Chao , Yang Ping-Zhen , Gao Jing-Wei , Li Ze-Hua
Published: July 2024

Background

Non-alcoholic fatty liver disease (NAFLD) has emerged as a predominant driver of chronic liver disease globally and is associated with increased cardiovascular disease morbidity and mortality. However, the association between NAFLD and calcific aortic valve disease remains unclear. We aimed to prospectively investigate the association between NAFLD and incident aortic valve calcification (AVC), as well as its genetic relationship with incident calcific aortic valve stenosis (CAVS).

Methods

A post hoc analysis was conducted on 4226 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) database. We employed the adjusted Cox models to assess the observational association between NAFLD and incident AVC. Additionally, we conducted two-sample Mendelian randomization (MR) analyses to investigate the genetic association between genetically predicted NAFLD and calcific aortic valve stenosis (CAVS), a severe form of CAVD. We repeated the MR analyses by excluding NAFLD susceptibility genes linked to impaired very low-density lipoprotein (VLDL) secretion.

Results

After adjustment for potential risk factors, participants with NAFLD had a hazard ratio of 1.58 (95% CI: 1.03–2.43) for incident AVC compared to those without NAFLD. After excluding genes associated with impaired VLDL secretion, the MR analyses consistently showed the significant associations between genetically predicted NAFLD and CAVS for 3 traits: chronic elevation of alanine aminotransferase (odds ratio = 1.13 [95% CI: 1.01–1.25]), imaging-based NAFLD (odds ratio = 2.81 [95% CI: 1.66–4.76]), and biopsy-confirmed NAFLD (odds ratio = 1.12 [95% CI: 1.01–1.24]). However, the association became non-significant when considering all NAFLD susceptibility genes.

Conclusions

NAFLD was independently associated with an elevated risk of incident AVC. Genetically predicted NAFLD was also associated with CAVS after excluding genetic variants related to impaired VLDL secretion.
Genetically predicted metabolites mediate the causal associations between autoimmune thyroiditis and immune cells
Authors: Chen Yongzhao , Jiang Bo , Qu Cheng , Jiang Chaoyu , Zhang Chen , Wang Yanxue , Chen Fei , Sun Xitai , Su Lei , Luo Yuqian
Published: July 2024

Introduction

We aimed to comprehensively investigate the causal relationship between 731 immune cell traits and autoimmune thyroiditis (AIT) and to identify and quantify the role of 1400 metabolic traits as potential mediators in between.

Methods

Using summary-level data from genome-wide association studies (GWAS) we performed a two-sample bidirectional Mendelian randomization (MR) analysis of genetically predicted AIT and 731 immune cell traits. Furthermore, we used a two-step MR analysis to quantify the proportion of the total effects (that the immune cells exerted on the risk of AIT) mediated by potential metabolites.

Results

We identified 24 immune cell traits (with odds ratio (OR) ranging from 1.3166 6 to 0.6323) and 10 metabolic traits (with OR ranging from 1.7954 to 0.6158) to be causally associated with AIT, respectively. Five immune cell traits (including CD38 on IgD+ CD24-, CD28 on CD28+ CD45RA+ CD8br, HLA DR+ CD4+ AC, TD CD4+ %CD4+, and CD8 on EM CD8br) were found to be associated with the risk of AIT, which were partially mediated by metabolites (including glycolithocholate sulfate, 5alpha-androstan-3alpha,17beta-diol disulfate, arachidonoylcholine, X-15486, and kynurenine). The proportion of genetically predicted AIT mediated by the identified metabolites could range from 5.58% to 17.7%.

Discussion

Our study identified causal associations between AIT and immune cells which were partially mediated by metabolites, thus providing guidance for future clinical and basic research.
Enhancing spatial modeling and risk mapping of six air pollutants using synthetic data integration with convolutional neural networks
Authors: Bashardoost Abed , Mesgari Mohammad Saadi , Karimi Mina
Published: July 2024

Air pollution poses significant risks to human health and the environment, necessitating effective air quality management strategies. This study presents a novel approach to air quality management by integrating an autoencoder (AE) with a convolutional neural network (CNN) algorithm in Tehran city of Iran. One of the primary and vital problems in deep learning is model complexity, and the complexity of a model is affected by data distribution, data complexity, and information volume. AE provide a helpful way to denoise input data and make building deep learning models much more efficient. The proposed methodology enables spatial modeling and risk mapping of six air pollutants, namely, particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO). For air pollution modelling, data from a spatial database containing the annual average of six pollutants from 2012 to 2022 was utilized. The model considered various parameters influencing air pollution: altitude, humidity, distance to industrial areas, NDVI (normalized difference vegetation index), population density, rainfall, distance to the street, temperature, traffic volume, wind direction, and wind speed. The risk map accuracy was assessed using the area under the receiver operating characteristic (ROC) curve for six pollutants. Among them, NO2, PM10, CO, PM2.5, O3, and SO2 exhibited the highest accuracy with values of 0.964, 0.95, 0.896, 0.878, 0.877, and 0.811, respectively, in the risk map generated by the CNN-AE model. The findings demonstrated the CNN-AE model’s impressive precision when generating the pollution risk map.
The association of metabolic syndrome with telomere length as a marker of cellular aging: a systematic review and meta-analysis
Authors: Ibraheem Shelash Al-Hawary Sulieman , Ali Alzahrani Abdullah , Ghaleb Maabreh Hatem , Abed Jawad Mohammed , Alsaadi Salim B. , Kareem Jabber Noura , Alawadi Ahmed , Alsalamy Ali , Alizadeh Farideh
Published: July 2024

Background

It has been suggested that metabolic syndrome (MetS) accelerates the aging process, potentially contributing to the development of age-related complications. Available studies examining the relation of MetS to telomere length (TL), a putative biological marker of aging, have yielded inconclusive findings. This meta-analysis was performed to investigate the association between MetS and TL.

Methods

A comprehensive systematic search was conducted in PubMed and Scopus databases to identify relevant literature published up to February 2024. Standard mean difference (SMD) and standardized beta coefficient (β) with their 95% confidence intervals (CI) were used as effect sizes to measure the associations using the random effects model.

Results

A total of nine studies, comprising a total sample size of 8,606 participants, were eligible for the meta-analysis. No significant difference in mean TL was found between patients with and without MetS (SMD = −0.03, 95%CI = −0.17 to 0.10), with a significant heterogeneity across the studies (I2 = 89.7.0%, p ≤ 0.001). In contrast, it was revealed that MetS is negatively related to TL (β = −0.08, 95%CI = −0.15 to −0.004). In the subgroup analysis, this finding was supported by the International Diabetes Federation (IDF) definition of MetS.

Conclusion

This meta-analysis highlighted that MetS may be linked to a shorter TL. Additional studies are required to confirm this finding.
Alternative splicing responses to salt stress in Glycyrrhiza uralensis revealed by global profiling of transcriptome RNA-seq datasets
Authors: Yao Hua , Li Guozhi , Gao Zhuanzhuan , Guo Fei , Feng Jianghua , Xiao Guanghui , Shen Haitao , Li Hongbin
Published: July 2024

Excessive reactive oxygen species stress due to salinity poses a significant threat to the growth of Glycyrrhiza uralensis Fisch. To adapt to salt stress, G. uralensis engages in alternative splicing (AS) to generate a variety of proteins that help it withstand the effects of salt stress. While several studies have investigated the impact of alternative splicing on plants stress responses, the mechanisms by which AS interacts with transcriptional regulation to modulate the salt stress response in G. uralensis remain poorly understood. In this study, we utilized high-throughput RNA sequencing data to perform a comprehensive analysis of AS events at various time points in G. uralensis under salt stress, with exon skipping (SE) being the predominant AS type. KEGG enrichment analysis was performed on the different splicing genes (DSG), and pathways associated with AS were significantly enriched, including RNA transport, mRNA surveillance, and spliceosome. This indicated splicing regulation of genes, resulting in AS events under salt stress conditions. Moreover, plant response to salt stress pathways were also enriched, such as mitogen-activated protein kinase signaling pathway – plant, flavonoid biosynthesis, and oxidative phosphorylation. We focused on four differentially significant genes in the MAPK pathway by AS and qRT-PCR analysis. The alternative splicing type of MPK4 and SnRK2 was skipped exon (SE). ETR2 and RbohD were retained intron (RI) and alternative 5’splice site (A5SS), respectively. The expression levels of isoform1 of these four genes displayed different but significant increases in different tissue sites and salt stress treatment times. These findings suggest that MPK4, SnRK2, ETR2, and RbohD in G. uralensis activate the expression of isoform1, leading to the production of more isoform1 protein and thereby enhancing resistance to salt stress. These findings suggest that salt-responsive AS directly and indirectly governs G. uralensis salt response. Further investigations into AS function and mechanism during abiotic stresses may offer novel references for bolstering plant stress tolerance.
The complete chloroplast genome sequences of nine melon varieties (Cucumis melo L.): lights into comparative analysis and phylogenetic relationships
Authors: Hu Jianpeng , Yao Jinchen , Lu Jimei , Liu Weiwei , Zhao Zhiqiang , Li Yaqian , Jiang Lu , Zha Liangping
Published: July 2024

Melon (Cucumis melo L.) is one of the most extensively grown horticulture crops of the world. Based on the morphological characters, melon was formerly divided into two subspecies, Cucumis melo ssp. melo and C. melo ssp. agrestis. However, the present methods are still inadequate to distinguish between them. The phylogenetic analysis based on chloroplast genome sequences could provide essential evidence for the classification of melon varieties. We sequenced the chloroplast genomes of nine different melon varieties by the Illumina Hiseq and performed bioinformatic analyses including repeat element analysis, genome comparison and phylogenetic analysis. The results showed that the melon chloroplast genome has a typical quadripartite structure that was conserved across the analyzed sequences. Its length ranges between 155, 558 and 156, 569 bp, with a total GC content varying from 36.7% to 37%. We found 127–132 genes in melon chloroplast genomes, including 85–87 protein-coding regions, 34–37 tRNA and 6-8 rRNA genes. The molecular structure, gene order, content, codon usage, long repeats, and simple sequence repeats (SSRs) were mostly conserved among the nine sequenced genomes. Phylogenetic analysis showed that the chloroplast genome could clearly distinguish between C. melo ssp. melo and C. melo ssp. agrestis. This study not only provides valuable knowledge on melon chloroplasts, but also offers a theoretical basis and technical support for the genetic breeding of melons.
Daily habits, diseases, drugs and knee osteoarthritis: a two-sample Mendelian randomization analysis
Authors: Zhou Yaqiong , Wang Qi , Chen Liping , Bo Yun , Zhang Yuanyuan
Published: July 2024

Background

The causal relationship between daily habits, diseases, drugs, and knee osteoarthritis (KOA) remains unclear. This study utilized a two-sample Mendelian randomization (MR) method to investigate the causal links between these factors and KOA, providing new insights for KOA prevention.

Methods

SNPs strongly associated with exposure factors (daily habits, diseases, drugs) were extracted from publicly available genome-wide association study (GWAS) as instrumental variables (IVs). We then selected GWAS of KOA as the outcome, conducting a two-sample MR analysis.

Results

Our findings revealed significant causal relationships between several factors and KOA. There was a notable association with time spent watching TV (OR = 4.038; 95% CI: 1.859–8.770; P = 4.192E-04), frequency of friend/family visits (OR = 0.415; 95% CI: 0.219–0.788; P = 7.174E-03), smoking history (OR = 0.781; 95% CI: 0.663–0.921; P = 3.235E-03), gastroesophageal reflux disease (GERD) (OR = 1.519; 95% CI: 1.244–1.856; P = 4.183E-05), hypercholesterolemia (OR = 0.498; 95% CI: 0.290–0.855; P = 0.011), hypothyroidism (OR = 1.048; 95% CI: 1.013–1.084; P = 6.645E-03), use of antithrombotic agents (OR = 0.892; 95% CI: 0.816–0.976; P = 0.013), statin medication (OR = 0.956; 95% CI: 0.916–0.998; P = 0.041), and thyroid preparations (OR = 1.042; 95% CI: 1.014–1.071; P = 2.974E-03) with KOA. Specifically, KOA was positively associated with longer time spent watching TV, GERD, hypothyroidism and thyroid preparations, however showed a negative correlation with more frequent visits from friends or family, smoking history, hypercholesterolemia, antithrombotic agents and statin medication. Sensitivity analysis indicated no significant pleiotropy in these studies (P > 0.05).

Conclusion

This comprehensive study underscores the significance of modifying certain habits to mitigate the risk of KOA. Additionally, the elevated risk of KOA among individuals with GERD, hypothyroidism, and those using thyroid preparations warrants attention. These results would be beneficial for clinical research and nursing education.
HapKled: a haplotype-aware structural variant calling approach for Oxford nanopore sequencing data
Authors: Zhang Zhendong , Liu Yue , Li Xin , Liu Yadong , Wang Yadong , Jiang Tao
Published: July 2024

Introduction: Structural Variants (SVs) are a type of variation that can significantly influence phenotypes and cause diseases. Thus, the accurate detection of SVs is a vital part of modern genetic analysis. The advent of long-read sequencing technology ushers in a new era of more accurate and comprehensive SV calling, and many tools have been developed to call SVs using long-read data. Haplotype-tagging is a procedure that can tag haplotype information on reads and can thus potentially improve the SV detection; nevertheless, few methods make use of this information. In this article, we introduce HapKled, a new SV detection tool that can accurately detect SVs from Oxford Nanopore Technologies (ONT) long-read alignment data.

Methods: HapKled utilizes haplotype information underlying alignment data by conducting haplotype-tagging using Whatshap on the reads to improve the detection performance, with three unique calling mechanics including altering clustering conditions according to haplotype information of signatures, determination of similar SVs based on haplotype information, and slack filtering conditions based on haplotype quality.

Results: In our evaluations, HapKled outperformed state-of-the-art tools and can deliver better SV detection results on both simulated and real sequencing data. The code and experiments of HapKled can be obtained from https://github.com/CoREse/HapKled.

Discussion: With the superb SV detection performance that HapKled can deliver, HapKled could be useful in bioinformatics research, clinical diagnosis, and medical research and development.
Treatment of rosacea with upadacitinib and abrocitinib: case report and review of evidence for Janus kinase inhibition in rosacea
Authors: Zhang Ting , Liu Xu , Zhang Lu , Jiang Xian
Published: July 2024

Introduction

Conventional rosacea treatments are not uniformly pervasive, and the adverse reactions can potentially constrain their utility. The clinical use of JAK1 inhibitors upadacitinib and abrocitinib in the treatment of refractory rosacea has rarely been explored.

Case report

We presented two cases of patients who received the JAK1 inhibitor upadacitinib and four cases of patients who received the JAK1 inhibitor abrocitinib for the treatment of refractory rosacea.

Discussion

The JAK1 inhibitors upadacitinib and abrocitinib may be promising medical options for patients with refractory rosacea. However, the long-term safety and efficacy of upadacitinib and abrocitinib require prospective controlled studies to assess them more comprehensively.
Tumor associated macrophages in breast cancer progression: implications and clinical relevance
Authors: Stavrou Maria , Constantinidou Anastasia
Published: July 2024

Macrophages represent an immune cell population characterized by high plasticity and a range of properties and functions. Their activation status and specific phenotype are highly associated with their localization and the environmental cues they receive. The roles of macrophages in cancer development are diverse. Despite their antitumor effects at early stages of the disease, their presence in the tumor microenvironment (TME) has been linked to tumor promotion upon disease establishment. Tumor associated macrophages (TAMs) are key components of breast cancer TME and they have been associated with poor clinical outcomes. High TAM densities were found to correlate with tumor progression, increased metastatic potential and poor prognosis. Interestingly, considerably higher levels of TAMs were found in patients with triple negative breast cancer (TNBC)—the most aggressive type of breast cancer—compared to other types. The present review summarizes recent findings regarding the distinct TAM subsets in the TME and TAM involvement in breast cancer progression and metastasis. It highlights the constant interplay between TAMs and breast cancer cells and its major contribution to the progression of the disease, including such aspects as, polarization of macrophages toward a tumor promoting phenotype, induction of epithelial to mesenchymal transition (EMT) in cancer cells and enhancement of cancer stem cell properties. Further, we discuss the clinical relevance of these findings, focusing on how a better delineation of TAM involvement in breast cancer metastasis will facilitate the selection of more efficient treatment options.
Seismic oceanography of internal solitary waves offshore the South Island, New Zealand
Authors: Meng Linghan , Zhang Kun , Song Haibin , Liu Mengli
Published: July 2024

Seismic oceanography has been widely used in the study of internal solitary waves (ISWs) in recent years, and has achieved remarkable results. In this paper, we analyzed the multi-channel seismic reflection data in the Canterbury Basin offshore New Zealand from January 9 to January 29, 2000, collected by R/V Maurice Ewing. We observed 4 groups of ISWs (labeled ISW1s to ISW4s) on 4 seismic survey lines. We studied their waveforms and propagation speeds in detail. There are two theoretical structures used to describe the vertical waveform of ISWs: the first-order nonlinear vertical structure and the linear vertical structure. We found that ISW1s fit the nonlinear structure well, ISW3s and ISW4s fit the linear structure, and ISW2 does not fit either one. As the water depth increases, the waveforms of all ISWs gradually widen. Two satellite SAR images reveal that all ISWs generally travel shoreward across the isobaths. However, the propagation direction of ISW1s is about 354°-360° (clockwise from due north), different from the propagation directions of other ISWs (about 22°-26°), which explains why ISW1s have the largest characteristic half-height width. The estimated propagation speeds are close to the theoretical speeds, confirming our speed correction method. In the end, we also discuss the interaction of ISWs and eddies.
Current challenges and improvements in assessing the immunogenicity of bacterial vaccines
Authors: Fantoni Giulia , Boccadifuoco Giuseppe , Verdirosa Federica , Molesti Eleonora , Manenti Alessandro , Montomoli Emanuele
Published: July 2024

The increase in antimicrobial-resistant bacterial strains has highlighted the need for a new vaccine strategy. The primary goal of a candidate vaccine is to prevent disease, by inducing a persistent immunologic memory, through the activation of pathogen-specific immune response. Antibody titer is the main parameter used to assess the immunogenicity of bacterial vaccine candidates and it is the most widely used as a correlate of protection. On the other hand, the antibody titer alone cannot provide complete information on all the activity mediated by antibodies which can only be assessed by functional assays, like the serum bactericidal assay and the opsonophagocytosis assay. However, due to the involvement of many biological factors, these assays are difficult to standardize. Some improvements have been achieved in recent years, but further optimizations are needed to minimize inter- and intra-laboratories variability and to allow the applicability of these functional assays for the vaccine immunogenicity assessment on a larger scale.
Temporal dynamics and species-level complexity of Prevotella spp. in the human gut microbiota: implications for enterotypes and health
Authors: Han Na , Peng Xianhui , Zhang Tingting , Qiang Yujun , Li Xiuwen , Zhang Wen
Published: July 2024

The concept of “enterotypes” in microbiome research has attracted substantial interest, particularly focusing on the abundance of Prevotella spp. in the human gut. In this study, the intricate dynamics of Prevotella spp. in the human gut microbiota was investigated, based on the metagenomic method. First, 239 fecal samples from individuals across four regions of China revealed a bimodal distribution, highlighting the abundance and variability in Prevotella spp. within the Chinese population. Second, the longitudinal cohort study included 184 fecal samples from 52 time points collected from seven individuals who demonstrated either the outbreaks or disappearances of Prevotella spp., emphasizing the transient nature of Prevotella abundance levels and suggesting shifts in Prevotella “enterotypes.” Furthermore, a turnover of the dominant Prevotella spp. was observed, indicating the potential presence of diverse subtypes of Prevotella enterotype. Notably, the genomic analysis demonstrated the persistence of specific Prevotella strains within individuals over extended periods, highlighting the enduring presence of Prevotella in the human gut. In conclusion, by integrating the temporal and geographical scales in our research, we gained deeper insights into the dynamics of Prevotella, emphasizing the importance of considering the dynamics at the time and species level in gut microbiota studies and their implications on human health.
Identification of potential nucleomodulins of Mycoplasma bovis by direct biotinylation and proximity-based biotinylation approaches
Authors: Lu Doukun , Chen Jiongxi , Zhang Menghan , Fu Yingjie , Raheem Abdul , Chen Yingyu , Chen Xi , Hu Changmin , Chen Jianguo , Schieck Elise , Zhao Gang , Guo Aizhen
Published: July 2024

Mycoplasma bovis (M. bovis) is a significant bovine pathogen associated with various diseases, including bovine bronchopneumonia and mastitis resulting in substantial economic losses within the livestock industry. However, the development of effective control measures for M. bovis is hindered by a limited understanding of its virulence factors and pathogenesis. Nucleomodulins are newly identified secreted proteins of bacteria that internalize the host nuclei to regulate host cell gene expression and serve as critical virulence factors. Although recent reports have initiated exploration of mycoplasma nucleomodulins, the efficiency of conventional techniques for identification is very limited. Therefore, this study aimed to establish high-throughput methods to identify novel nucleomodulins of M. bovis. Using a direct biotinylation (DB) approach, a total of 289 proteins were identified including 66 high abundant proteins. In parallel, the use of proximity-based biotinylation (PBB), identified 28 proteins. Finally, seven nucleomodulins were verified to be nuclear by transfecting the bovine macrophage cell line BoMac with the plasmids encoding EGFP-fused proteins and observed with Opera Phenix, including the known nucleomodulin MbovP475 and six novel nucleomodulins. The novel nucleomodulins were four ribosomal proteins (MbovP599, MbovP678, MbovP710, and MbovP712), one transposase (MbovP790), and one conserved hypothetical protein (MbovP513). Among them, one unique nucleomodulin MbovP475 was identified with DB, two unique nucleomodulins (MbovP513 and MbovP710) with PBB, and four nucleomodulins by both. Overall, these findings established a foundation for further research on M. bovis nucleomodulin-host interactions for identification of new virulence factors.
Integrating bioinformatics and multiple machine learning to identify mitophagy-related targets for the diagnosis and treatment of diabetic foot ulcers: evidence from transcriptome analysis and drug docking
Authors: Guo Hui , Xiao Kui , Zheng Yanhua , Zong Jianchun
Published: July 2024

Background

Diabetic foot ulcers are the most common and serious complication of diabetes mellitus, the high morbidity, mortality, and disability of which greatly diminish the quality of life of patients and impose a heavy socioeconomic burden. Thus, it is urgent to identify potential biomarkers and targeted drugs for diabetic foot ulcers.

Methods

In this study, we downloaded datasets related to diabetic foot ulcers from gene expression omnibus. Dysregulation of mitophagy-related genes was identified by differential analysis and weighted gene co-expression network analysis. Multiple machine algorithms were utilized to identify hub mitophagy-related genes, and a novel artificial neural network model for assisting in the diagnosis of diabetic foot ulcers was constructed based on their transcriptome expression patterns. Finally, potential drugs that can target hub mitophagy-related genes were identified using the Enrichr platform and molecular docking methods.

Results

In this study, we identified 702 differentially expressed genes related to diabetic foot ulcers, and enrichment analysis showed that these genes were associated with mitochondria and energy metabolism. Subsequently, we identified hexokinase-2, small ribosomal subunit protein us3, and l-lactate dehydrogenase A chain as hub mitophagy-related genes of diabetic foot ulcers using multiple machine learning algorithms and validated their diagnostic performance in a validation cohort independent of the present study (The areas under roc curve of hexokinase-2, small ribosomal subunit protein us3, and l-lactate dehydrogenase A chain are 0.671, 0.870, and 0.739, respectively). Next, we constructed a novel artificial neural network model for the molecular diagnosis of diabetic foot ulcers, and the diagnostic performance of the training cohort and validation cohort was good, with areas under roc curve of 0.924 and 0.840, respectively. Finally, we identified retinoic acid and estradiol as promising anti-diabetic foot ulcers by targeting hexokinase-2 (−6.6 and −7.2 kcal/mol), small ribosomal subunit protein us3 (−7.5 and −8.3 kcal/mol), and l-lactate dehydrogenase A chain (−7.6 and −8.5 kcal/mol).

Conclusion

The present study identified hexokinase-2, small ribosomal subunit protein us3 and l-lactate dehydrogenase A chain, and emphasized their critical roles in the diagnosis and treatment of diabetic foot ulcers through multiple dimensions, providing promising diagnostic biomarkers and targeted drugs for diabetic foot ulcers.
Functional relationship between peripheral thermosensation and behavioral thermoregulation
Authors: Suito Takuto , Tominaga Makoto
Published: July 2024

Thermoregulation is a fundamental mechanism for maintaining homeostasis in living organisms because temperature affects essentially all biochemical and physiological processes. Effector responses to internal and external temperature cues are critical for achieving effective thermoregulation by controlling heat production and dissipation. Thermoregulation can be classified as physiological, which is observed primarily in higher organisms (homeotherms), and behavioral, which manifests as crucial physiological functions that are conserved across many species. Neuronal pathways for physiological thermoregulation are well-characterized, but those associated with behavioral regulation remain unclear. Thermoreceptors, including Transient Receptor Potential (TRP) channels, play pivotal roles in thermoregulation. Mammals have 11 thermosensitive TRP channels, the functions for which have been elucidated through behavioral studies using knockout mice. Behavioral thermoregulation is also observed in ectotherms such as the fruit fly, Drosophila melanogaster. Studies of Drosophila thermoregulation helped elucidate significant roles for thermoreceptors as well as regulatory actions of membrane lipids in modulating the activity of both thermosensitive TRP channels and thermoregulation. This review provides an overview of thermosensitive TRP channel functions in behavioral thermoregulation based on results of studies involving mice or Drosophila melanogaster.
Stochastic electrical stimulation of the thoracic or cervical regions with surface electrodes facilitates swallow in rats
Authors: Kitamura In , Frazure Michael , Iceman Kimberly , Koike Takuji , Pitts Teresa
Published: July 2024

Introduction

Aspiration pneumonia, a leading cause of mortality, poses an urgent challenge in contemporary society. Neuromuscular electrical stimulation (NMES) has been commonly used in dysphagia rehabilitation. However, given that NMES at motor threshold targets only specific muscles, it carries a potential risk of further compromising functions related to swallowing, respiration, and airway protection. Considering that the swallow motor pattern is orchestrated by the entire swallow pattern generator (the neural mechanism governing a sequence of swallow actions), a rehabilitation approach that centrally facilitates the entire circuit through sensory nerve stimulation is desirable. In this context, we propose a novel stimulation method using surface electrodes placed on the back to promote swallowing.

Methods

The efficacy of the proposed method in promoting swallowing was evaluated by electrically stimulating sensory nerves in the back or neck. Probabilistic stimulus was applied to either the back or neck of male and female rats. Swallows were evoked by an oral water stimulus, and electromyographic (EMG) activity of the mylohyoid, thyroarytenoid, and thyropharyngeus muscles served as the primary outcome measure.

Results

Gaussian frequency stimulation applied to the skin surface of the thoracic back elicited significant increases in EMG amplitude of all three swallow-related muscles. Neck stimulation elicited a significant increase in EMG amplitude of the thyroarytenoid during swallow, but not the mylohyoid or thyropharyngeus muscles.

Discussion

While the targeted thoracic spinal segments T9-T10 have been investigated for enhancing respiration, the promotion of swallowing through back stimulation has not been previously studied. Furthermore, this study introduces a new probabilistic stimulus based on Gaussian distribution. Probabilistic stimuli have been reported to excel in nerve stimulation in previous research. The results demonstrate that back stimulation effectively facilitated swallow more than neck stimulation and suggest potential applications for swallowing rehabilitation.
Effects of the feeding protocol during blood transfusion on splanchnic tissue oxygenation and complications in very premature infants
Authors: He Jianghua , Sun Xueshi , Xu Xiaoming , Luo Hanwen , Tang Jun , Xiong Tao , Zhao Jing , Shi Jing
Published: July 2024

Background

The effects of blood transfusions on splanchnic oxygenation and complications related to blood transfusions, including red blood cell (RBC) transfusions, in premature infants undergoing enteral feeding, to provide clinical evidence for a management protocol for premature infants during the peri-transfusion period.

Methods

This single-blind, randomized, controlled trial enrolled sixty eligible preterm infants who were randomly divided into the withholding feeding group (n = 30) or feeding group (n = 30). Enteral feeding was withheld for 8 h, beginning from the start of transfusion infants in the feeding group were fed according to the pre-transfusion feeding approach during and after RBC transfusion.

Results

Baseline characteristics of those in the withholding and feeding groups were as follows: gestational age (weeks) 27.52 (24.86–30.14) and 27.13 (25.43–30.14); birth weight (g), 1,027 (620–1,450) and 1,027 (620–1,270); blood transfusion day, 48 (14–79) and 39 (10–78); and hemoglobin before blood transfusion (g/L), 81.67 (±10.56) and 85.93 (±14.77). No significant differences were observed between groups at baseline. No significant differences were observed in the average splanchnic tissue oxygenation changes or clinical results at any time. One patient in the withholding feeding group experienced transfusion-associated necrotizing enterocolitis.

Conclusions

No differences in splanchnic oxygenation observed these feeding protocols. This study suggests the feasibility of a sizable trial to evaluate clinical outcomes. The risks of mesenteric ischemia and transfusion-related necrotizing enterocolitis for premature infants were not increased by enteral feeding during RBC transfusion.

Clinical trial registration

ChiCTR2200055726 (https://www.chictr.org.cn/).
High-purity 1,2-dimyristoyl-sn-glycero-3-phosphocholine: synthesis and emulsifying performance evaluation
Authors: Kim Se-Young , Park Ye-Lim , Ji Ha-Eun , Lee Hae-Se , Chang Hyeon-Jun , Bang Gyeong-Hee , Lee Jeung-Hee
Published: July 2024

Introduction

1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) is a promising emulsifier for bioactive delivery systems, but its industrial applications are limited by the lack of cost-effective and scalable synthetic routes. The purpose of this study was to economically produce high-purity DMPC by replacing commonly used column chromatography methods and to evaluate the emulsifying performance.

Methods

DMPC was synthesized from sn-glycero-3-phosphocholine using Steglich esterification followed by sequential recrystallization from ethyl acetate and acetone. The structure of DMPC was identified and its purity was confirmed using various spectroscopy and chromatography techniques. The emulsifying performance was evaluated by examining the effects of storage on the properties of o/w emulsions prepared using soybean oil with (i) soy PC, (ii) soy PC + DMPC (1:1, w/w), and (iii) DMPC as emulsifiers.

Results

The chemical impurities formed during the synthesis of DMPC was removed, and its final purity was 96%, and the melt transition temperature was 37.6°C. No visible difference between the three emulsions (soy PC, soy PC+DMPC, and DMPC) was observed during two-week storage, and the DMPC-based emulsion was more stable than soy PC emulsion, showing smaller particle size distribution during 6 months.

Discussion

The highly pure DMPC was synthesized by an economical method, and DMPC-based emulsions demonstrated physicochemical stable, highlighting its potential for food and pharmaceutical industry-related applications. Our findings suggest that DMPC holds promise as an emulsifier with broad applications in the food industry.
The impact of dietary preference on household food waste: evidence from China
Authors: Zhang Li , Ye Linxiang , Qian Long , Zuo Xiuping
Published: July 2024

Food waste jeopardizes food security and causes economic and resource losses. Household food waste is the most significant source of global food waste and urgently needs to be reduced. Based on the China Health and Nutrition Survey (CHNS), our study estimates the daily food waste data of 6,418 sample observations across China and the dietary preference scores of their household heads. Using a count regression model, our study explores the relationship between dietary preference and household food waste in Chinese households, and further explores the moderating function of household refrigerator use. The study has found that: (1) improving dietary preference score can significantly reduce household food waste ratio, and robustness tests support this finding. (2) There is a positive moderating effect of refrigerator use in the process of how dietary preference influence food waste. (3) Heterogeneity analysis shows that the impact of dietary preference on household food waste varies by gender and age of the household head, household size, economic level, urban–rural type, and north–south region. Our study provides evidence that improving dietary preference can reduce household food waste in China, which has certain implications for waste reduction in other developing countries.