bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial impact of urban expansion on lake surface water temperature based on the perspective of watershed scale
Authors: Tang Linfeng , Yang Kun , Shang Chunxue , Peng Zongqi , Luo Yi
Published: August 2022

As an important ecological environmental factor, the lake water surface temperature (LSWT) has an important impact on the ecological diversity of lakes and watersheds. With the acceleration of urbanization in China, the impact of urban expansion on LSWT can not be ignored. In this study, we introduced the spatial influence(G) equation, selected MOD11A2, impervious surface (IS), digital elevation model (DEM) and Landsat series remote sensing images as data sources, and took six lakes with rapid urban expansion in China as the empirical research object to explore the variation characteristics of urban expansion and LSWT in six lake watersheds and the spatial influence of urban expansion on LSWT. Finally, the following conclusions can be drawn: The results show that 1) The IS in the six watersheds all experienced significant expansion, with an increase of 1.80–3.91 times. 2) From the annual average LSWT from 2001 to 2018, only Poyang Lake’s LSWT-night shows a cooling trend, while other lakes, whether LSWT-day or LSWT-night, show a warming trend. 3) G is used to comprehensively consider the area change of IS in the watershed, the influence of distance and the change of lake area, which can quantify the impact of IS on LSWT, so as to further explain and describe the spatial influence process and characteristics of IS expansion on LSWT.
Movement and olfactory signals: Sexually dimorphic antennae and female flightlessness in moths
Authors: Johnson Tamara L. , Elgar Mark A. , Symonds Matthew R. E.
Published: August 2022

Darwin argued a role for sexual selection in the evolution of male sensory structures, including insect antennae, the strength of which will depend upon the importance of early arrival at receptive females. There is remarkable variation in the nature and degree of sexual dimorphism in moth antennae, with males of some species having spectacular, feathery antennae. Although it is widely assumed that these elaborate structures provide greater sensitivity to chemical signals (sex pheromones), the factors underlying the interspecific diversity in male antennal structure and size are poorly understood. Because male antennal morphology may be affected by several female life–history traits, including flight ability, we conducted a phylogenetic comparative analysis to test how these traits are linked, using data from 93 species of moths across 11 superfamilies. Our results reveal that elaborate antennae in males have evolved more frequently in species where females are monandrous. Further, female loss of flight ability evolved more frequently in species where males have elaborate antennae. These results suggest that elaborate antennae have evolved in response to more intense male competition, arising from female monandry, and that the evolution of elaborate antennae in males has, in turn, shaped the evolution of female flightlessness.
Serum differential proteomic profiling of patients with isolated methylmalonic acidemia by iTRAQ
Authors: Li Sitao , Shi Congcong , Cai Yao , Gu Xia , Xiong Hui , Liu Xiaoyu , Zhang Yinchun , Xiao Xin , Ma Fei , Hao Hu
Published: August 2022

Isolated methylmalonic acidemia (MMA) is an inherited organic acid metabolic disorder in an autosomal recessive manner, caused by mutations in the methylmalonyl coenzyme A mutase gene, and the isolated MMA patients often suffer from multi-organ damage. The present study aimed to profile the differential proteome of serum between isolated MAA patients and healthy control. The in vivo proteome of isolated MAA patients and healthy subjects was detected by an isobaric tag for relative and absolute quantitation (iTRAQ). A total of 94 differentially expressed proteins (DEPs) were identified between MMA patients and healthy control, including 58 upregulated and 36 downregulated DEPs in MMA patients. Among them, the most significantly upregulated proteins were CRP and immunoglobulins, and the top five most significantly downregulated proteins were all different types of immunoglobulins in MMA patients. GO analysis showed that these DEPs were mainly enriched in immune-related function and membrane protein-related function. KEGG revealed that these DEPs were mainly enriched in lysosome and cholesterol metabolism pathways. Also, these DEPs were predicted to contribute to lipid metabolic diseases. We addressed the proteomes of isolated MMA patients and identified DEPs. Our study expands our current understanding of MMA, and the DEPs could be valuable for designing alternative therapies to alleviate MMA symptoms.
A pyroptosis-related gene signature for prognosis and immune microenvironment of pancreatic cancer
Authors: Tao Sifan , Tian Li , Wang Xiaoyan , Shou Yajun
Published: August 2022

Pancreatic cancer is one of the most lethal tumors owing to its unspecific symptoms during the early stage and multiple treatment resistances. Pyroptosis, a newly discovered gasdermin-mediated cell death, facilitates anti- or pro-tumor effects in a variety of cancers, whereas the impact of pyroptosis in pancreatic cancer remains unclear. Therefore, we downloaded RNA expression and clinic data from the TCGA-PAAD cohort and were surprised to find that most pyroptosis-related genes (PRGs) are not only overexpressed in tumor tissue but also strongly associated with overall survival. For their remarkable prognostic value, cox regression analysis and lasso regression were used to establish a five-gene signature. All patients were divided into low- and high-risk groups based on the media value of the risk score, and we discovered that low-risk patients had better outcomes in both the testing and validation cohorts using time receiver operating characteristic (ROC), nomograms, survival, and decision analysis. More importantly, a higher somatic mutation burden and less immune cell infiltration were found in the high-risk group. Following that, we predicted tumor response to chemotherapy and immunotherapy in both low- and high-risk groups, which suggests patients with low risk were more likely to respond to both immunotherapy and chemotherapy. To summarize, our study established an effective model that can help clinicians better predict patients’ drug responses and outcomes, and we also present basic evidence for future pyroptosis related studies in pancreatic cancer.
CENP-A is a potential prognostic biomarker and correlated with immune infiltration levels in glioma patients
Authors: Yang Yuan , Duan Mengyun , Zha Yunfei , Wu Zijun
Published: August 2022

Background: Centromeric protein A (CENP-A), an essential protein involved in chromosomal segregation during cell division, is associated with several cancer types. However, its role in gliomas remains unclear. This study examined the clinical and prognostic significance of CENP-A in gliomas.

Methods: Data of patients with glioma were collected from the Cancer Genome Atlas. Logistic regression, the Kruskal–Wallis test, and the Wilcoxon signed-rank test were performed to assess the relationship between CENP-A expression and clinicopathological parameters. The Cox regression model and Kaplan–Meier curve were used to analyze the association between CENP-A and survival outcomes. A prognostic nomogram was constructed based on Cox multivariate analysis. Gene set enrichment analysis (GSEA) was conducted to identify key CENP-A-related pathways and biological processes.

Results:CENP-A was upregulated in glioma samples. Increased CENP-A levels were significantly associated with the world health organization (WHO) grade [Odds ratio (OR) = 49.88 (23.52–129.06) for grade 4 vs. grades 2 and 3], primary therapy outcome [OR = 2.44 (1.64–3.68) for progressive disease (PD) and stable disease (SD) vs. partial response (PR) and complete response (CR)], isocitrate dehydrogenase (IDH) status [OR = 13.76 (9.25–20.96) for wild-type vs. mutant], 1p/19q co-deletion [OR = 5.91 (3.95–9.06) for no codeletion vs. co-deletion], and age [OR = 4.02 (2.68–6.18) for > 60 vs. ≤ 60]. Elevated CENP-A expression was correlated with shorter overall survival in both univariate [hazard ratio (HR): 5.422; 95% confidence interval (CI): 4.044–7.271; p < 0.001] and multivariate analyses (HR: 1.967; 95% CI: 1.280–3.025; p < 0.002). GSEA showed enrichment of numerous cell cycle-and tumor-related pathways in the CENP-A high expression phenotype. The calibration plot and C-index indicated the favorable performance of our nomogram for prognostic prediction in patients with glioma.

Conclusion: We propose a role for CENP-A in glioma progression and its potential as a biomarker for glioma diagnosis and prognosis.
Genetic diversity analysis and development of molecular markers for the identification of largemouth bass (Micropterus salmoides L.) based on whole-genome re-sequencing
Authors: Du Jinxing , Li Shengjie , Shao Jiaqi , Song Hongmei , Jiang Peng , Lei Caixia , Bai Junjie , Han Linqiang
Published: August 2022

Largemouth bass (Micropterus salmoides L.) is generally considered to comprise two subspecies, Florida bass (M. floridanus) and Northern Largemouth bass (M. salmoides), which have biological characteristic differences because of their geographical distribution. In this study, whole-genome re-sequencing was performed among 10 Florida and 10 Northern largemouth bass, respectively. In total, 999,793 SNPs and 227,797 InDels were finally identified, and 507,401 SNPs (50.75%) and 116,213 InDels (51.01%) were successfully mapped to annotated 18,629 genes and 14,060 genes, respectively. KEGG classification indicated that most of these genes were focused on the pathways including signal transduction, transport and catabolism, and endocrine system. Genetic diversity analysis indicated that Florida largemouth bass had higher genetic diversity than Northern largemouth bass, indicating that the germplasm quality of Northern largemouth bass had markedly reduced in China. To examine the accuracies of the identified markers, 23 SNPs and eight InDels (the insertions or deletions of more than 45 bp) were randomly selected and detected among Florida largemouth bass, Northern largemouth bass, and their F1 hybrids. The detection efficiencies of all the markers were higher than 95%; nineteen SNPs and three InDels could accurately distinguish the two subspecies and their F1 hybrids with 100% efficiencies. Moreover, the three InDel markers could clearly distinguish the two subspecies and their F1 hybrids with a PCR-based agarose gel electrophoresis. In conclusion, our study established a simple PCR-based method for the germplasm identification of largemouth bass, which will be useful in the germplasm protection, management, and hybridization breeding of largemouth bass.
miR-22-3p as a potential biomarker for coronary artery disease based on integrated bioinformatics analysis
Authors: Zhang Minghua , Hu Yan , Li Haoda , Guo Xiaozi , Zhong Junhui , He Sha
Published: August 2022

Background: Coronary artery disease (CAD) is a common cardiovascular disease that has attracted attention worldwide due to its high morbidity and mortality. Recent studies have shown that abnormal microRNA (miRNA) expression is effective in CAD diagnoses and processes. However, the potential relationship between miRNAs and CAD remains unclear.

Methods: Microarray datasets GSE105449 and GSE28858 were downloaded directly from the Gene Expression Omnibus (GEO) to identify miRNAs involved in CAD. Target gene prediction and enrichment analyses were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).

Results: There were nine differentially expressed miRNAs in CAD patients compared to the controls. A total of 352 genes were predicted and subjected to GO analysis, which showed that differentially expressed genes (DEGs) were mainly associated with axon guidance, neuron projection guidance, neuron-to-neuron synapses, and postsynaptic density. According to the KEGG pathway analysis, the most enriched pathways were those involved in transcriptional misregulation in cancer, growth hormone synthesis, secretion and action, endocrine resistance, axon guidance, and Cushing syndrome. Pathway analysis was mainly involved in the HIPPO and prion disease signaling pathways. Furthermore, a competing endogenous RNA (ceRNA) interaction network centered on miR-22-3p revealed eight related transcription factors in the cardiovascular system. The receiver operating characteristic (ROC) curve analysis suggested that miR-22-3p may be a better CAD predictor.

Conclusion: The results indicate that miR-22-3p may function in pathophysiological CAD processes. Our study potentiates miR-22-3p as a specific biomarker for diagnosing CAD.
Hierarchical identification of a transcriptional panel for the histological diagnosis of lung neuroendocrine tumors
Authors: Zhang Juxuan , Deng Jiaxing , Feng Xiao , Tan Yilong , Li Xin , Liu Yixin , Li Mengyue , Qi Haitao , Tang Lefan , Meng Qingwei , Yan Haidan , Qi Lishuang
Published: August 2022

Background: Lung cancer is a complex disease composed of neuroendocrine (NE) and non-NE tumors. Accurate diagnosis of lung cancer is essential in guiding therapeutic management. Several transcriptional signatures have been reported to distinguish between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) belonging to non-NE tumors. This study aims to identify a transcriptional panel that could distinguish the histological subtypes of NE tumors to complement the morphology-based classification of an individual.

Methods: A public dataset with NE subtypes, including 21 small-cell lung cancer (SCLC), 56 large-cell NE carcinomas (LCNECs), and 24 carcinoids (CARCIs), and non-NE subtypes, including 85 ADC and 61 SCC, was used as a training set. In the training set, consensus clustering was first used to filter out the samples whose expression patterns disagreed with their histological subtypes. Then, a rank-based method was proposed to develop a panel of transcriptional signatures for determining the NE subtype for an individual, based on the within-sample relative gene expression orderings of gene pairs. Twenty-three public datasets with a total of 3,454 samples, which were derived from fresh-frozen, formalin-fixed paraffin-embedded, biopsies, and single cells, were used for validation. Clinical feasibility was tested in 10 SCLC biopsy specimens collected from cancer hospitals via bronchoscopy.

Results: The NEsubtype-panel was composed of three signatures that could distinguish NE from non-NE, CARCI from non-CARCI, and SCLC from LCNEC step by step and ultimately determine the histological subtype for each NE sample. The three signatures achieved high average concordance rates with 97.31%, 98.11%, and 90.63%, respectively, in the 23 public validation datasets. It is worth noting that the 10 clinic-derived SCLC samples diagnosed via immunohistochemical staining were also accurately predicted by the NEsubtype-panel. Furthermore, the subtype-specific gene expression patterns and survival analyses provided evidence for the rationality of the reclassification by the NEsubtype-panel.

Conclusion: The rank-based NEsubtype-panel could accurately distinguish lung NE from non-NE tumors and determine NE subtypes even in clinically challenging samples (such as biopsy). The panel together with our previously reported signature (KRT5-AGR2) for SCC and ADC would be an auxiliary test for the histological diagnosis of lung cancer.
Analyzing network diversity of cell–cell interactions in COVID-19 using single-cell transcriptomics
Authors: Wang Xinyi , Almet Axel A. , Nie Qing
Published: August 2022

Cell–cell interactions (CCI) play significant roles in manipulating biological functions of cells. Analyzing the differences in CCI between healthy and diseased conditions of a biological system yields greater insight than analyzing either conditions alone. There has been a recent and rapid growth of methods to infer CCI from single-cell RNA-sequencing (scRNA-seq), revealing complex CCI networks at a previously inaccessible scale. However, the majority of current CCI analyses from scRNA-seq data focus on direct comparisons between individual CCI networks of individual samples from patients, rather than “group-level” comparisons between sample groups of patients comprising different conditions. To illustrate new biological features among different disease statuses, we investigated the diversity of key network features on groups of CCI networks, as defined by different disease statuses. We considered three levels of network features: node level, as defined by cell type; node-to-node level; and network level. By applying these analysis to a large-scale single-cell RNA-sequencing dataset of coronavirus disease 2019 (COVID-19), we observe biologically meaningful patterns aligned with the progression and subsequent convalescence of COVID-19.
Case report: Cystic hygroma accompanied with campomelic dysplasia in the first trimester caused by haploinsufficiency with SOX9 deletion
Authors: Liu Xijing , Wang Jianmin , Yang Mei , Tian Tian , Hu Ting
Published: August 2022

Introduction: Campomelic dysplasia (CD) is a rare autosomal dominant skeletal malformation syndrome characterized by shortness and bowing of the lower extremities with or without XY sex reversal. Diagnosis using ultrasonography is most often made in the latter half of pregnancy. Intragenic heterozygous mutations in SOX9 are responsible for most cases of CD. CD caused by SOX9 deletion is a rare condition.

Case presentation: We present a single case report of an individual with cystic hygroma accompanied by CD, which was detected by ultrasound in the first trimester. Chromosomal microarray analysis (CMA) was performed to determine copy number variants, whereas whole exome sequencing (WES) was performed to elucidate single-nucleotide variants. Chorionic villus sampling was performed to enable such analyses. Ultimately, CMA detected a 606 kb deletion in the 17q24.3 region with only one protein-coding gene (SOX9). However, no mutation in the SOX9 protein-coding sequence was detected by WES.

Conclusion: When cystic hygroma is detected, prenatal diagnoses for skeletal dysplasia by ultrasound are likely to be confirmed in the first trimester. We propose a comprehensive prenatal diagnostic strategy that combines CMA and WES to diagnose fetuses with cystic hygroma accompanied by skeletal dysplasia.
Integrated transcriptome and hormone analyses provide insights into silver thiosulfate-induced “maleness” responses in the floral sex differentiation of pumpkin (Cucurbita moschata D.)
Authors: Li Qingfei , Chen Peiwen , Tang Hao , Zeng Fansen , Li Xinzheng
Published: August 2022

The perfect mating of male and female flowers is the key to successful pollination. The regulation of ethylene with chemicals is a good option for inducing staminate or female flowers. Silver thiosulfate is often used to induce the formation of male flowers in subgynoecious and gynoecious crops, which is important to maintain their progenies. However, its effects on flower sex differentiation in pumpkin (Cucurbita moschata Duch.) and the underlying mechanism remain unclear. In this study, the application of silver thiosulfate to pumpkin seedlings significantly delayed the occurrence of the first female flower and increased the number of male flowers. We next investigated the underlying mechanism by employing transcriptome and endogenous hormone analyses of the treated plants. In total, 1,304 annotated differentially expressed genes (DEGs)were identified by comparing silver thiosulfate-treated and control plants. Among these genes, 835 were upregulated and 469 were downregulated. The DEGs were mainly enriched in the phenylpropanoid biosynthesis and metabolism pathways (phenylalanine ammonia-lyase, peroxidase) and plant hormone signal transduction pathways (auxin signaling, indole-3-acetic acid-amido synthetase, ethylene response factor). Silver thiosulfate significantly reduced the levels of 2-oxindole-3-acetic acid, para-topolin riboside, dihydrozeatin-O-glucoside riboside, and jasmonoyl-l-isoleucine but increased the levels of trans-zeatin-O-glucoside, cis-zeatin riboside, and salicylic acid 2-O-β-glucoside. The levels of auxin and jasmonic acid were decreased, whereas those of salicylic acid were increased. Different trends were observed for different types of cytokinins. We concluded that silver thiosulfate treatment not only affects the expression of auxin synthesis and signaling genes but also that of ethylene response factor genes and regulates the levels of auxin, salicylic acid, jasmonic acid, and cytokinins, which together might contribute to the maleness of pumpkin. This study provides useful information for understanding the mechanism underlying the effect of silver thiosulfate on floral sex differentiation in pumpkin, a widely cultivated vegetable crop worldwide, and gives a production guidance for the induction of maleness using STS for the reproduction of gynoecious lines of Cucurbitaceae crops.
An integrative analysis of DNA methylation and gene expression to predict lung adenocarcinoma prognosis
Authors: Xu Liexi , Huang Zhengrong , Zeng Zihang , Li Jiali , Xie Hongxin , Xie Conghua
Published: August 2022

Background: Abnormal DNA methylation of gene promoters is an important feature in lung adenocarcinoma (LUAD). However, the prognostic value of DNA methylation remains to be further explored. Objectives. We sought to explore DNA methylation characteristics and develop a quantifiable criterion related to DNA methylation to improve survival prediction for LUAD patients.

Methods: Illumina Human Methylation450K array data, level 3 RNA-seq data and corresponding clinical information were obtained from TCGA. Cox regression analysis and the Akaike information criterion were used to construct the best-prognosis methylation signature. Receiver operating characteristic curve analysis was used to validate the prognostic ability of the DNA methylation-related feature score. qPCR was used to measure the transcription levels of the identified genes upon methylation.

Results: We identified a set of DNA methylation features composed of 11 genes (MYEOV, KCNU1, SLC27A6, NEUROD4, HMGB4, TACR3, GABRA5, TRPM8, NLRP13, EDN3 and SLC34A1). The feature score, calculated based on DNA methylation features, was independent of tumor recurrence and TNM stage in predicting overall survival. Of note, the combination of this feature score and TNM stage provided a better overall survival prediction than either of them individually. The transcription levels of all the hypermethylated genes were significantly increased after demethylation, and the expression levels of 3 hypomethylated proteins were significantly higher in tumor tissues than in normal tissues, as indicated by immunohistochemistry data from the Human Protein Atlas. Our results suggested that these identified genes with prognostic features were regulated by DNA methylation of their promoters.

Conclusion: Our studies demonstrated the potential application of DNA methylation markers in the prognosis of LUAD.
Multisite assessment of the impact of cell-free DNA-based screening for rare autosomal aneuploidies on pregnancy management and outcomes
Authors: Mossfield Tamara , Soster Erica , Menezes Melody , Agenbag Gloudi , Dubois Marie-Line , Gekas Jean , Hardy Tristan , Jurkowska Monika , Kleinfinger Pascale , Loggenberg Kelly , Marchili Pablo , Sirica Roberto ,   on behalf of the Global Expanded NIPT Consortium
Published: August 2022

Cell-free (cf) DNA screening is a noninvasive prenatal screening approach that is typically used to screen for common fetal trisomies, with optional screening for sex chromosomal aneuploidies and fetal sex. Genome-wide cfDNA screening can screen for a wide variety of additional anomalies, including rare autosomal aneuploidies (RAAs) and copy number variants. Here, we describe a multi-cohort, global retrospective study that looked at the clinical outcomes of cases with a high-risk cfDNA screening result for a RAA. Our study cohort included a total of 109 cases from five different sites, with diagnostic outcome information available for 68% (74/109) of patients. Based on confirmatory diagnostic testing, we found a concordance rate of 20.3% for presence of a RAA (15/74) in our study population. Pregnancy outcome was also available for 77% (84/109) of cases in our cohort. Many of the patients experienced adverse pregnancy outcomes, including intrauterine fetal demise, fetal growth restriction, and preterm birth. These adverse outcomes were observed both in patients with fetal or placental confirmation of the presence of a RAA, as well as patients that did not undergo fetal and/or placental diagnostic testing. In addition, we have proposed some suggestions for pregnancy management and counseling considerations for situations where a RAA is noted on a cfDNA screen. In conclusion, our study has shown that genome-wide cfDNA screening for the presence of rare autosomal aneuploidies can be beneficial for both patients and their healthcare practitioners. This can provide a possible explanation for an adverse pregnancy outcome or result in a change in pregnancy management, such as increased monitoring for adverse outcomes.
Characterization of tumor immune microenvironment and cancer therapy for head and neck squamous cell carcinoma through identification of a genomic instability-related lncRNA prognostic signature
Authors: Jing Lijun , Du Yabing , Fu Denggang
Published: August 2022

Head and neck squamous cell carcinoma (HNSCC) represents one of the most prevalent and malignant tumors of epithelial origins with unfavorable outcomes. Increasing evidence has shown that dysregulated long non-coding RNAs (lncRNAs) correlate with tumorigenesis and genomic instability (GI), while the roles of GI-related lncRNAs in the tumor immune microenvironment (TIME) and predicting cancer therapy are still yet to be clarified. In this study, transcriptome and somatic mutation profiles with clinical parameters were obtained from the TCGA database. Patients were classified into GI-like and genomic stable (GS)-like groups according to the top 25% and bottom 25% cumulative counts of somatic mutations. Differentially expressed lncRNAs (DElncRNAs) between GI- and GS-like groups were identified as GI-related lncRNAs. These lncRNA-related coding genes were enriched in cancer-related KEGG pathways. Patients totaling 499 with clinical information were randomly divided into the training and validation sets. A total of 18 DElncRNAs screened by univariate Cox regression analysis were associated with overall survival (OS) in the training set. A GI-related lncRNA signature that comprised 10 DElncRNAs was generated through least absolute shrinkage and selection operator (Lasso)-Cox regression analysis. Patients in the high-risk group have significantly decreased OS vs. patients in the low-risk group, which was verified in internal validation and entire HNSCC sets. Integrated HNSCC sets from GEO confirmed the notable survival stratification of the signature. The time-dependent receiver operating characteristic curve demonstrated that the signature was reliable. In addition, the signature retained a strong performance of OS prediction for patients with various clinicopathological features. Cell composition analysis showed high anti-tumor immunity in the low-risk group which was evidenced by increased infiltrating CD8+ T cells and natural killer cells and reduced cancer-associated fibroblasts, which was convinced by immune signatures analysis via ssGSEA algorithm. T helper/IFNγ signaling, co-stimulatory, and co-inhibitory signatures showed increased expression in the low-risk group. Low-risk patients were predicted to be beneficial to immunotherapy, which was confirmed by patients with progressive disease who had high risk scores vs. complete remission patients. Furthermore, the drugs that might be sensitive to HNSCC were identified. In summary, the novel prognostic GILncRNA signature provided a promising approach for characterizing the TIME and predicting therapeutic strategies for HNSCC patients.
Plasma vesicular miR-155 as a biomarker of immune activation in antiretroviral treated people living with HIV
Authors: Bazié Wilfried Wenceslas , Boucher Julien , Goyer Benjamin , Traoré Isidore Tiandiogo , Kania Dramane , Somé Diane Yirgnur , Alary Michel , Gilbert Caroline
Published: August 2022

People living with HIV (PLWH), despite suppression of viral replication with antiretroviral therapy (ART), have high morbidity and mortality due to immune activation and chronic inflammation. Discovering new biomarkers of immune activation status under ART will be pertinent to improve PLWH quality of life when the majority will be treated. We stipulate that plasma large and small extracellular vesicle (EVs) and their microRNA content could be easily measured biomarkers to monitor immune activation in PLWH. Venous blood samples from n = 128 ART-treated PLWH with suppressed viral load (≤ 20 copies/mL) and n = 60 HIV-uninfected participants were collected at five testing or treatment centers of PLWH in Burkina Faso. Large and small plasma EVs were purified, counted, and the mature miRNAs miR-29a, miR-146a, and miR-155 were quantified by RT-qPCR. Diagnostic performances of large and small EVs miRNAs level were evaluated by receiver operating characteristic (ROC) curve analysis and principal component analysis (PCA). Among the EVs microRNA measured, only large EVs miR-155 copies distinguished PLWH with immune activation, with AUC of 0.75 for CD4/CD8 < 1 (95% CI: 0.58–0.91, P = 0.0212), and 0.77 for CD8 T cells ≥ 500/µL (95% CI: 0.63–0.92, P = 0.0096). In addition, PCA results suggest that large EVs miR-155 copies may be a biomarker of immune activation. Since miR-155 may influence immune cell function, its enrichment in large EV subpopulations could be a functional biomarker of immune activation in PLWH on ART. This measure could help to monitor and diagnose the immune activation with more accuracy.
Efficacy of umbilical cord mesenchymal stromal cells for COVID-19: A systematic review and meta-analysis
Authors: Yang Cong-wen , Chen Ru-dong , Zhu Qing-run , Han Shi-jie , Kuang Ming-jie
Published: August 2022

Objectives

A major challenge for COVID-19 therapy is dysregulated immune response associated with the disease. Umbilical cord mesenchymal stromal cells (UC-MSCs) may be a promising candidate for COVID-19 treatment owing to their immunomodulatory and anti-inflammatory functions. Therefore, this study aimed to evaluate the effectiveness of UC-MSCs inpatients with COVID-19.

Method

Medline, Embase, PubMed, Cochrane Library, and Web of Science databases were searched to collect clinical trials concerning UC-MSCs for the treatment of COVID-19. After literature screening, quality assessment, and data extraction, a systematic review and meta-analysis of the included study were performed.

Results

This systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022304061. After screening, 10 studies involving 293 patients with COVID-19 were eventually included. Our meta-analysis results showed that UC-MSCs can reduce mortality (relative risk [RR] =0.60, 95% confidence interval [CI]: [0.38, 0.95], P=0.03) in COVID-19 patients. No significant correlation was observed between adverse events and UC-MSC treatment (RR=0.85, 95% CI: [0.65, 1.10], P=0.22; RR=1.00, 95%CI: [0.64, 1.58], P=1.00). In addition, treatment with UC-MSCs was found to suppress inflammation and improve pulmonary symptoms.

Conclusions

UC-MSCs hold promise as a safe and effective treatment for COVID-19.

Systematic Review Registartion

PROSPERO, identifier CRD42022304061
Single-cell gene expression analysis of cryopreserved equine bronchoalveolar cells
Authors: Sage Sophie E. , Nicholson Pamela , Peters Laureen M. , Leeb Tosso , Jagannathan Vidhya , Gerber Vinzenz
Published: August 2022

The transcriptomic profile of a cell population can now be studied at the cellular level using single-cell mRNA sequencing (scRNA-seq). This novel technique provides the unprecedented opportunity to explore the cellular composition of the bronchoalveolar lavage fluid (BALF) of the horse, a species for which cell type markers are poorly described. Here, scRNA-seq technology was applied to cryopreserved equine BALF cells. Analysis of 4,631 cells isolated from three asthmatic horses in remission identified 16 cell clusters belonging to six major cell types: monocytes/macrophages, T cells, B/plasma cells, dendritic cells, neutrophils and mast cells. Higher resolution analysis of the constituents of the major immune cell populations allowed deep annotation of monocytes/macrophages, T cells and B/plasma cells. A significantly higher lymphocyte/macrophage ratio was detected with scRNA-seq compared to conventional cytological differential cell count. For the first time in horses, we detected a transcriptomic signature consistent with monocyte-lymphocyte complexes. Our findings indicate that scRNA-seq technology is applicable to cryopreserved equine BALF cells, allowing the identification of its major (cytologically differentiated) populations as well as previously unexplored T cell and macrophage subpopulations. Single-cell gene expression analysis has the potential to facilitate understanding of the immunological mechanisms at play in respiratory disorders of the horse, such as equine asthma.
Nomogram based on circulating lymphocyte subsets for predicting radiation pneumonia in esophageal squamous cell carcinoma
Authors: Zhang Xiao-zhen , Tao Su-ping , Liang Shi-xiong , Chen Shu-bin , Liu Fu-shuang , Jiang Wei , Chen Mao-jian
Published: August 2022

Purpose

Currently, the relationship between radiation pneumonia (RP) and circulating immune cell in patients with esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to explore the relationship between RP and circulating lymphocyte subsets in patients with ESCC receiving chemoradiotherapy (CRT), and develop a nomogram model to predict RP. Since we should implement clinical intervention to ≥ grade 2 RP, a nomogram model for ≥ grade 2 RP was also established to provide an early warning.

Patients and methods

This study retrospectively included 121 patients with ESCC receiving CRT from Guangxi Medical University Cancer Hospital from 2013 to 2021. Independent factors associated with occurrence of RP and ≥ grade 2 RP were identified by univariate and multivariate logistic regression analysis in the training cohort, and incorporated into nomograms. The predictive accuracy and discrimination of the model was assessed using Concordance Index (C-index), calibration curve and decision curve analysis (DCA). And each model was internally validated. Additionally, to verify the optimized predictive performance of the nomograms, the area under the ROC curve (AUC) of each nomogram was compared to that of single independent risk factors, lung V10 and lung V20, respectively. Moreover, each model was further evaluated for risk stratification to identify populations at high risk of RP and ≥ grade 2 RP.

Results

Multivariate analysis suggested that TNM stage, post-RT percentage of CD8+ T cell, and lung V15 were independent predictive factors of RP. Besides, pre- and post-RT percentage of CD8+ T cell, and V15 were independent factors of ≥ grade 2 RP. The C-indexes of RP and ≥ grade 2 RP nomograms were 0.809 (95% CI: 0.715-0.903) and 0.787 (95% CI: 0.685-0.889) in the training cohort, respectively. And the C-indexes of RP and ≥ grade 2 RP nomograms were 0.718 (95% CI: 0.544-0.892) and 0.621 (95% CI: 0.404-0.837) in the validation cohort, respectively. The calibration curves showed that the predicted values of model agreed well with actual observations. Moreover, DCA results indicated the applicability and accuracy of the models to predict RP and ≥ grade 2 RP. After stratification, the incidence of the high-risk group was significantly higher than that of the low-risk group with respect to either RP or ≥ grade 2 RP.

Conclusion

TNM stage, post-RT percentage of CD8+ T cell, and lung V15 were the independent predictors of RP toxicity. Pre- and post-RT percentage of CD8+ T cell, and lung V15 were the independent factors of ≥ grade 2 RP toxicity. The nomograms based on circulating lymphocyte subsets can robustly predict RP and ≥ grade 2 RP, guiding clinicians in risk stratification and early intervention.
Microglia subtypes show substrate- and time-dependent phagocytosis preferences and phenotype plasticity
Authors: Li Shuailong , Wernersbach Isa , Harms Gregory S. , Schäfer Michael K. E.
Published: August 2022

Microglia are phagocytosis-competent CNS cells comprising a spectrum of subtypes with beneficial and/or detrimental functions in acute and chronic neurodegenerative disorders. The heterogeneity of microglia suggests differences in phagocytic activity and phenotype plasticity between microglia subtypes. To study these issues, primary murine glial cultures were cultivated in the presence of serum, different growth factors and cytokines to obtain M0-like, M1-like, and M2-like microglia as confirmed by morphology, M1/M2 gene marker expression, and nitric oxide assay. Single-cell analysis after 3 hours of phagocytosis of E.coli particles or IgG-opsonized beads showed equal internalization by M0-like microglia, whereas M1-like microglia preferably internalized E.coli particles and M2-like microglia preferably internalized IgG beads, suggesting subtype-specific preferences for different phagocytosis substrates. Time-lapse live-cells imaging over 16 hours revealed further differences between microglia subtypes in phagocytosis preference and internalization dynamics. M0- and, more efficiently, M1-like microglia continuously internalized E.coli particles for 16 hours, whereas M2-like microglia discontinued internalization after approximately 8 hours. IgG beads were continuously internalized by M0- and M1-like microglia but strikingly less by M2-like microglia. M2-like microglia initially showed continuous internalization similar to M0-like microglia but again discontinuation of internalization after 8 hours suggesting that the time of substrate exposure differently affect microglia subtypes. After prolonged exposure to E.coli particles or IgG beads for 5 days all microglia subtypes showed increased internalization of E.coli particles compared to IgG beads, increased nitric oxide release and up-regulation of M1 gene markers, irrespectively of the phagocytosis substrate, suggesting phenotype plasticity. In summary, microglia subtypes show substrate- and time-dependent phagocytosis preferences and phenotype plasticity. The results suggest that prolonged phagocytosis substrate exposure enhances M1-like profiles and M2-M1 repolarization of microglia. Similar processes may also take place in conditions of acute and chronic brain insults when microglia encounter different types of phagocytic substrates.
The parasitic worm product ES-62 protects the osteoimmunology axis in a mouse model of obesity-accelerated ageing
Authors: Harnett Margaret M. , Doonan James , Lumb Felicity E. , Crowe Jenny , Damink Roel Olde , Buitrago Geraldine , Duncombe-Moore Josephine , Wilkinson Debbie I. , Suckling Colin J. , Selman Colin , Harnett William
Published: August 2022

Despite significant increases in human lifespan over the last century, adoption of high calorie diets (HCD) has driven global increases in type-2 diabetes, obesity and cardiovascular disease, disorders precluding corresponding improvements in healthspan. Reflecting that such conditions are associated with chronic systemic inflammation, evidence is emerging that infection with parasitic helminths might protect against obesity-accelerated ageing, by virtue of their evolution of survival-promoting anti-inflammatory molecules. Indeed, ES-62, an anti-inflammatory secreted product of the filarial nematode Acanthocheilonema viteae, improves the healthspan of both male and female C57BL/6J mice undergoing obesity-accelerated ageing and also extends median lifespan in male animals, by positively impacting on inflammatory, adipose metabolic and gut microbiome parameters of ageing. We therefore explored whether ES-62 affects the osteoimmunology axis that integrates environmental signals, such as diet and the gut microbiome to homeostatically regulate haematopoiesis and training of immune responses, which become dysregulated during (obesity-accelerated) ageing. Of note, we find sexual dimorphisms in the decline in bone health, and associated dysregulation of haematopoiesis and consequent peripheral immune responses, during obesity-accelerated ageing, highlighting the importance of developing sex-specific anti-ageing strategies. Related to this, ES-62 protects trabecular bone structure, maintaining bone marrow (BM) niches that counter the ageing-associated decline in haematopoietic stem cell (HSC) functionality highlighted by a bias towards myeloid lineages, in male but not female, HCD-fed mice. This is evidenced by the ability of ES-62 to suppress the adipocyte and megakaryocyte bias and correspondingly promote increases in B lymphocytes in the BM. Furthermore, the consequent prevention of ageing-associated myeloid/lymphoid skewing is associated with reduced accumulation of inflammatory CD11c+ macrophages and IL-1β in adipose tissue, disrupting the perpetuation of inflammation-driven dysregulation of haematopoiesis during obesity-accelerated ageing in male HCD-fed mice. Finally, we report the ability of small drug-like molecule analogues of ES-62 to mimic some of its key actions, particularly in strongly protecting trabecular bone structure, highlighting the translational potential of these studies.
Cancer cell membrane-wrapped nanoparticles for cancer immunotherapy: A review of current developments
Authors: Jiang Qi , Xie Mixue , Chen Ruyin , Yan Feifei , Ye Chanqi , Li Qiong , Xu Shuaishuai , Wu Wei , Jia Yunlu , Shen Peng , Ruan Jian
Published: August 2022

Background

As the forefront of nanomedicine, bionic nanotechnology has been widely used for drug delivery in order to obtain better efficacy but less toxicity for cancer treatments. With the rise of immunotherapy, the combination of nanotechnology and immunotherapy will play a greater potential of anti-tumor therapy. Due to its advantage of homologous targeting and antigen library from source cells, cancer cell membrane (CCM)-wrapped nanoparticles (CCNPs) has become an emerging topic in the field of immunotherapy.

Key scientific concepts of review

CCNP strategies include targeting or modulating the tumor immune microenvironment and combination therapy with immune checkpoint inhibitors and cancer vaccines. This review summarizes the current developments in CCNPs for cancer immunotherapy and provides insight into the challenges of transferring this technology from the laboratory to the clinic as well as the potential future of this technology.

Conclusion

This review described CCNPs have enormous potential in cancer immunotherapy, but there are still challenges in terms of translating their effects in vitro to the clinical setting. We believe that these challenges can be addressed in the future with a focus on individualized treatment with CCNPs as well as CCNPs combined with other effective treatments.
Safety and immunogenicity of BK-SE36 in a blinded, randomized, controlled, age de-escalating phase Ib clinical trial in Burkinabe children
Authors: Bougouma Edith Christiane , Palacpac Nirianne Marie Q. , Tiono Alfred B. , Nebie Issa , Ouédraogo Alphonse , Houard Sophie , Yagi Masanori , Coulibaly Sam Aboubacar , Diarra Amidou , Tougan Takahiro , Ouedraogo Amidou Z. , Soulama Issiaka , Arisue Nobuko , Yaro Jean Baptiste , D’Alessio Flavia , Leroy Odile , Cousens Simon , Horii Toshihiro , Sirima Sodiomon B.
Published: August 2022

Background

A blood-stage vaccine targeting the erythrocytic-stages of the malaria parasite Plasmodium falciparum could play a role to protect against clinical disease. Antibodies against the P. falciparum serine repeat antigen 5 (SE47 and SE36 domains) correlate well with the absence of clinical symptoms in sero-epidemiological studies. A previous phase Ib trial of the recombinant SE36 antigen formulated with aluminum hydroxyl gel (BK-SE36) was promising. This is the first time the vaccine candidate was evaluated in young children below 5 years using two vaccination routes.

Methods

Safety and immunogenicity of BK-SE36 was assessed in a double-blind, randomized, controlled, age de-escalating phase Ib trial. Fifty-four Burkinabe children in each age cohort, 25–60 or 12–24 months, were randomized in a 1:1:1 ratio to receive three doses of BK-SE36 either by intramuscular (BK IM) or subcutaneous (BK SC) route on Day 0, Week 4, and 26; or the control vaccine, Synflorix®via IM route on Day 0, Week 26 (and physiological saline on Week 4). Safety data and samples for immunogenicity analyses were collected at various time-points.

Results

Of 108 subjects, 104 subjects (96.3%) (Cohort 1: 94.4%; Cohort 2: 98.1%) received all three scheduled vaccine doses. Local reactions, mostly mild or of moderate severity, occurred in 99 subjects (91.7%). The proportion of subjects that received three doses without experiencing Grade 3 adverse events was similar across BK-SE36 vaccines and control arms (Cohort 1: 100%, 89%, and 89%; and Cohort 2: 83%, 82%, and 83% for BK IM, BK SC, and control, respectively). BK-SE36 vaccine was immunogenic, inducing more than 2-fold change in antibody titers from pre-vaccination, with no difference between the two vaccination routes. Titers waned before the third dose but in both cohorts titers were boosted 6 months after the first vaccination. The younger cohort had 2-fold and 4-fold higher geometric mean titers compared to the 25- to 60-month-old cohort after 2 and 3 doses of BK-SE36, respectively.

Conclusion

BK-SE36 was well tolerated and immunogenic using either intramuscular or subcutaneous routes, with higher immune response in the younger cohort.

Clinical Trial Registration

https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=934, identifier PACTR201411000934120.
Targeting the Cbl-b-Notch1 axis as a novel immunotherapeutic strategy to boost CD8+ T-cell responses
Authors: Monticone Giulia , Huang Zhi , Csibi Fred , Leit Silvana , Ciccone David , Champhekar Ameya S. , Austin Jermaine E. , Ucar Deniz A. , Hossain Fokhrul , Ibba Salome V. , Boulares A. Hamid , Carpino Nicholas , Xu Keli , Majumder Samarpan , Osborne Barbara A. , Loh Christine , Miele Lucio
Published: August 2022

A critical feature of cancer is the ability to induce immunosuppression and evade immune responses. Tumor-induced immunosuppression diminishes the effectiveness of endogenous immune responses and decreases the efficacy of cancer immunotherapy. In this study, we describe a new immunosuppressive pathway in which adenosine promotes Casitas B-lineage lymphoma b (Cbl-b)-mediated Notch1 degradation, causing suppression of CD8+ T-cells effector functions. Genetic knockout and pharmacological inhibition of Cbl-b prevents Notch1 degradation in response to adenosine and reactivates its signaling. Reactivation of Notch1 results in enhanced CD8+ T-cell effector functions, anti-cancer response and resistance to immunosuppression. Our work provides evidence that targeting the Cbl-b-Notch1 axis is a novel promising strategy for cancer immunotherapy.