bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing the supragingival microbiome of healthy pregnant women
Authors: Zhang Yangyang , Wu Zeyu , Li Ling , Wang Xiaohe , Fan Wenxian , Zhao Jin
Published: November 2022

The ecological characteristics and changes of the supragingival plaque microbial community during pregnancy are poorly understood. This study compared the microbial community characteristics of supragingival plaque in pregnant and non-pregnant women, with the aim of identifying specific microbial lineages and genera that may be associated with pregnancy. Thirty pregnant women were randomly selected from the First Affiliated Hospital of Xinjiang Medical University and divided into groups based on pregnancy trimester: first trimester (group P1, n=10, ≤12 weeks), second trimester (group P2, n=10, 13–27 weeks), and third trimester (group P3, n=10, 28–40 weeks). Ten healthy non-pregnant women (group N) were enrolled as the control group. Supragingival plaque samples of all subjects were collected and oral microbial composition was surveyed using a 16S rRNA gene sequencing approach. Statistical analysis was performed using a nonparametric test. The Chao 1 index of P3 was significantly lower compared with that of N, P1, and P2 (P<0.05). The Simpson indices of P2 and P3 were significantly higher than that of N (P<0.05). The Shannon index of P2 was significantly higher compared with that of N (P<0.05). Principal coordinate analysis (PCoA) showed different clustering according to the pregnancy status. Linear discriminant analysis effect size (LEfSe) revealed that the microbial species in group N that were significantly different from those of other groups were concentrated in the genus Neisseria. Species in P1 that were significantly different from those of other groups were concentrated in the genus Tannerella, while those in P2 and P3 were concentrated in the genus Leptotrichia. A total of 172 functional pathways were predicted for the bacterial communities in this study using PICRUSt2. Principal Component Analysis (PCA) showed that most predicted functional pathways clustered together in N and P1 and in P2 and P3. LEfSe analysis revealed that 11 pathways played a discriminatory role in the four groups. This work suggests a potential role of pregnancy in the formation of supragingival plaque microbiota and indicates that physiological changes during pregnancy may convert supragingival plaque into entities that could cause harm, which may be a risk factor for maternal health. Furthermore, findings from the study provide a basis for etiological studies of pregnancy-associated oral ecological disorders.
Transcriptional adaptation of staphylococci during colonization of the authentic human environment: An overview of transcriptomic changes and their relationship to physiological conditions
Authors: Burian Marc , Wolz Christiane , Yazdi Amir S.
Published: November 2022

Staphylococci are commensals of human skin and mucous membranes, but some species can also cause serious infections. Host niches during both colonization and infection differ greatly and are characterized by specific environmental conditions (pH, temperature, oxygen, nutrient availability, and microbiota) that can affect gene expression and virulence of microbes. To successfully occupy extremely different habitats at different anatomical sites, Staphylococci are equipped with a variety of regulatory elements that allow specific adaptation to the changing environments. Not surprisingly, gene expression in vivo can be significantly different from the expression pattern observed in vitro. Niche specific stimuli that influence the bacterial ability to either cause infection or maintain colonization are only partially understood. Here, we describe habitat specific conditions and discuss the available literature analyzing staphylococcal gene expression, focusing on Staphylococcus aureus and S. epidermidis during colonization of the nose and skin.
Predictive value of left ventricular dyssynchrony for short-term outcomes in three-vessel disease patients undergoing coronary artery bypass grafting with preserved or mildly reduced left ventricular ejection fraction
Authors: Liu Jia , Fan Rui , Li Cui-ling , Liu Yan-qiu , Liu Dong-hong , Li Wei , Yao Feng-juan
Published: November 2022

Background and objective

Coronary artery bypass grafting (CABG) is the reference standard intervention in coronary artery disease (CAD) patients with three-vessel disease (3VD). We aimed to evaluate the predictive value of left ventricular (LV) dyssynchrony for short-term adverse outcomes in patients with 3VD undergoing CABG with preserved or mildly reduced LV ejection fraction (LVEF).

Materials and methods

This study involved ninety-five 3VD patients with preserved or mildly reduced LVEF undergoing scheduled on-pump CABG. The pre-operative diameters and volumes of LV and LVEF were obtained by two-dimensional echocardiography. LV dyssynchrony parameters were acquired by real-time three-dimensional echocardiography (RT-3DE) and analyzed by HeartModel quantification software. And the perfusion index of LV was obtained by contrast echocardiography. The clinical endpoints of short-term adverse outcomes comprised 30-day mortality and/or composite outcomes of postoperative complications. Univariate and multivariate logistic regression analyses were used to identify risk factors for the occurrence of post-CABG short-term adverse outcomes.

Results

Short-term adverse outcomes occurred in 12 (12.6%) patients. These patients had higher LV dyssynchrony parameters obtained through RT-3DE. The standard deviation (SD) of the time to minimum systolic volume (Tmsv) corrected by heart rate over 16 segments (Tmsv16-SD%) [odds ratio (OR), 1.362; 95% confidence interval (CI) (1.090–1.702); P = 0.006], one of the LV dyssynchrony parameters, was independently associated with short-term adverse outcomes. Patients with poor synchronization tended to spend more time in the intensive care unit (ICU) and hospital after surgery.

Conclusion

Pre-operative LV dyssynchrony parameter Tmsv16-SD% obtained through RT-3DE could be a useful additional predictor of postoperative short-term adverse outcomes in 3VD patients with preserved or mildly reduced LVEF undergoing CABG.
Investigation on the differences of hemodynamics in normal common carotid, subclavian, and common femoral arteries using the vector flow technique
Authors: Song Di , Liu Mengmeng , Dong Yinghui , Hong Shaofu , Chen Ming , Du Yigang , Li Shuangshuang , Xu Jinfeng , Gao Wenjing , Dong Fajin
Published: November 2022

Objectives

To investigate the feasibility of the vector flow imaging (V Flow) technique to measure peripheral arterial hemodynamic parameters, including wall shear stress (WSS) and turbulence index (Tur) in healthy adults, and compare the results in different arteries.

Materials and methods

Fifty-two healthy adult volunteers were recruited in this study. The maximum and mean values of WSS, and the Tur values at early-systole, mid-systole, late-systole, and early diastole for total 156 normal peripheral arteries [common carotid arteries (CCA), subclavian arteries (SCA), and common femoral arteries (CFA)] were assessed using the V Flow technique.

Results

The mean WSS values for CCA, SCA, and CFA were (1.66 ± 0.68) Pa, (0.62 ± 0.30) Pa, and (0.56 ± 0.27) Pa, respectively. The mean Tur values for CCA, SCA, and CFA were (0.46 ± 1.09%), (20.7 ± 9.06%), and (24.63 ± 17.66%), respectively. The CCA and SCA, as well as the CCA and CFA, showed statistically significant differences in the mean WSS and the mean Tur (P < 0.01). The mean Tur values had a negative correlation with the mean WSS; the correlation coefficient between log(Tur) and WSS is −0.69 (P < 0.05).

Conclusion

V Flow technique is a simple, practical, and feasible quantitative imaging approach for assessing WSS and Tur in peripheral arteries. It has the potential to be a useful tool for evaluating atherosclerotic plaques in peripheral arteries. The results provide a new quantitative foundation for future investigations into diverse arterial hemodynamic parameters.
Auto-GNN: Neural architecture search of graph neural networks
Authors: Zhou Kaixiong , Huang Xiao , Song Qingquan , Chen Rui , Hu Xia
Published: November 2022

Graph neural networks (GNNs) have been widely used in various graph analysis tasks. As the graph characteristics vary significantly in real-world systems, given a specific scenario, the architecture parameters need to be tuned carefully to identify a suitable GNN. Neural architecture search (NAS) has shown its potential in discovering the effective architectures for the learning tasks in image and language modeling. However, the existing NAS algorithms cannot be applied efficiently to GNN search problem because of two facts. First, the large-step exploration in the traditional controller fails to learn the sensitive performance variations with slight architecture modifications in GNNs. Second, the search space is composed of heterogeneous GNNs, which prevents the direct adoption of parameter sharing among them to accelerate the search progress. To tackle the challenges, we propose an automated graph neural networks (AGNN) framework, which aims to find the optimal GNN architecture efficiently. Specifically, a reinforced conservative controller is designed to explore the architecture space with small steps. To accelerate the validation, a novel constrained parameter sharing strategy is presented to regularize the weight transferring among GNNs. It avoids training from scratch and saves the computation time. Experimental results on the benchmark datasets demonstrate that the architecture identified by AGNN achieves the best performance and search efficiency, comparing with existing human-invented models and the traditional search methods.
Raw material base of Russia’s unconventional oil and gas reserves (hydrocarbons shale strata)
Authors: Prischepa Oleg , Nefedov Yuri , Nikiforova Victoria , Ruiming Xu
Published: November 2022

One of the most controversial and discussed issues related to the development of the hydrocarbon raw material base in recent years is the issue of exploring the possibilities of involvement in industrial development accumulations associated with high-carbon shale complexes that are widespread in Russia. Interest therein is supported by the system of benefits provided by the Government for low-permeability reservoirs and special preferential conditions for geological exploration provided to subsurface users in recent years. An important effect was also achieved by developing a methodology for reserves assessment and placing on the state balance a whole series of fields with oil deposits in the Domanik formation of the Volga-Ural oil and gas province (OGP). Simultaneously, the assessment of the potential of high-carbon formations in the Russian Federation mainly continues to be the subject of scientific research without an applied component, due to its inapplicability for selecting both the most significant areas for exploration and the possibilities of using it to justify investments. Here, the uncertainty is related to the estimation of possible production levels with an unclear correlation between development technologies, filtration and reservoir properties, and the potential of high-carbon strata. This study discusses two approaches that allow assessment of the potential of the main high-carbon strata distributed in Russia.
Positive mass budgets of high-altitude and debris-covered fragmented tributary glaciers in Gangotri Glacier System, Himalaya
Authors: Hussain Md. Arif , Azam Mohd. Farooq , Srivastava Smriti , Vinze Parul
Published: November 2022

Glacier-wide mass balances (MBs) of the Gangotri, Chaturangi, Raktavaran, Meru, and Gangotri Glacier System are reconstructed with a temperature-index (T-index) model using bias-corrected ERA5 data at a daily temporal resolution over 1979–2020. The model output is calibrated against available geodetic MB for Gangotri Glacier System and validated with satellite-derived snow line altitudes (SLAs) for Gangotri Glacier. Gangotri and Meru glaciers show mean mass wastage of –0.88 ± 0.31 m w. e. a‒ˡ (meter water equivalent per year) and ‒0.17 ± 0.29 m w. e. a‒ˡ, respectively whereas the mass budgets of fragmented tributary Chaturangi and Raktavaran glaciers are positive with the mean values of 0.49 ± 0.17 m w. e. a‒ˡ and 0.62 ± 0.15 m w. e. a‒ˡ, respectively over 1979–2020. Gangotri Glacier’s tongue is covered by thick debris having several supra-glacial lakes and ice cliffs (considered as melting hotspots); therefore, despite the presence of thick debris, we assume the melting over this area as of a clean glacier. The whole Gangotri Glacier System shows a moderate wastage of ‒0.27 ± 0.25 m w. e. a‒ˡ. The positive MBs of the Raktavaran and Chaturangi glaciers are due to their high area-elevation distribution and heavily debris-covered tongues. The positive MBs on these fragmented tributary glaciers are due to non-climatic topographic reasons and should not be misunderstood as climate change deniers or compared with Karakoram Anomaly. Modelled MBs are most sensitive to the threshold temperature for melt. The altitudinal MB sensitivities to all model parameters become negligible above 6,200 m a.s.l.
Linear and nonlinear analyses of the association between low–density lipoprotein cholesterol and diabetes: The spurious U–curve in observational study
Authors: Ma Yujia , Zhou Zechen , Li Xiaoyi , Ding Kexin , Xiao Han , Wu Yiqun , Wu Tao , Chen Dafang
Published: November 2022

Objective

Hyperlipidemia is traditionally considered a risk factor for diabetes. The effect of low-density lipoprotein cholesterol (LDL-C) is counterintuitive to diabetes. We sought to investigate the relationship between LDL-C and diabetes for better lipid management.

Methods

We tested the shape of association between LDL-C and diabetes and created polygenic risk scores of LDL-C and generated linear Mendelian randomization (MR) estimates for the effect of LDL-C and diabetes. We evaluated for nonlinearity in the observational and genetic relationship between LDL-C and diabetes.

Results

Traditional observational analysis suggested a complex non-linear association between LDL-C and diabetes while nonlinear MR analyses found no evidence for a non-linear association. Under the assumption of linear association, we found a consistently protective effect of LDL-C against diabetes among the females without lipid-lowering drugs use. The ORs were 0.84 (95% CI, 0.72–0.97, P=0.0168) in an observational analysis which was more prominent in MR analysis and suggested increasing the overall distribution of LDL-C in females led to an overall decrease in the risk of diabetes (P=0.0258).

Conclusions

We verified the liner protective effect of LDL-C against diabetes among the females without lipid-lowering drug use. Non-linear associations between LDL-C against diabetes in observational analysis are not causal.
Microwell culture platform maintains viability and mass of human pancreatic islets
Authors: Kato Hiroyuki , Miwa Tatsuaki , Quijano Janine , Medrano Leonard , Ortiz Jose , Desantis Akiko , Omori Keiko , Wada Aya , Tatsukoshi Kentaro , Kandeel Fouad , Mullen Yoko , Ku Hsun Teresa , Komatsu Hirotake
Published: November 2022

Background

Transplantation of the human pancreatic islets is a promising approach for specific types of diabetes to improve glycemic control. Although effective, there are several issues that limit the clinical expansion of this treatment, including difficulty in maintaining the quality and quantity of isolated human islets prior to transplantation. During the culture, we frequently observe the multiple islets fusing together into large constructs, in which hypoxia-induced cell damage significantly reduces their viability and mass. In this study, we introduce the microwell platform optimized for the human islets to prevent unsolicited fusion, thus maintaining their viability and mass in long-term cultures.

Method

Human islets are heterogeneous in size; therefore, two different-sized microwells were prepared in a 35 mm-dish format: 140 µm × 300 µm-microwells for <160 µm-islets and 200 µm × 370 µm-microwells for >160 µm-islets. Human islets (2,000 islet equivalent) were filtered through a 160 µm-mesh to prepare two size categories for subsequent two week-cultures in each microwell dish. Conventional flat-bottomed 35 mm-dishes were used for non-filtered islets (2,000 islet equivalent/2 dishes). Post-cultured islets are collected to combine in each condition (microwells and flat) for the comparisons in viability, islet mass, morphology, function and metabolism. Islets from three donors were independently tested.

Results

The microwell platform prevented islet fusion during culture compared to conventional flat bottom dishes, which improved human islet viability and mass. Islet viability and mass on the microwells were well-maintained and comparable to those in pre-culture, while flat bottom dishes significantly reduced islet viability and mass in two weeks. Morphology assessed by histology, insulin-secreting function and metabolism by oxygen consumption did not exhibit the statistical significance among the three different conditions.

Conclusion

Microwell-bottomed dishes maintained viability and mass of human islets for two weeks, which is significantly improved when compared to the conventional flat-bottomed dishes.
Decreased expression of Glucagon-like peptide-1 receptor and Sodium-glucose co-transporter 2 in patients with proliferative diabetic retinopathy
Authors: Chen Hui , Zhang Xiongze , Liao Nanying , Ji Yuying , Mi Lan , Gan Yuhong , Su Yongyue , Wen Feng
Published: November 2022

Purpose

To investigate the expression of Glucagon-like peptide-1 receptor (GLP-1R), sodium-glucose co-transporter (SGLT) 1, SGLT2, Glucose transporter type 1 (GLUT1) and GLUT2 in patients with diabetic retinopathy (DR).

Methods

We obtained peripheral blood mononuclear cells (PBMCs) and vitreous samples from 26 proliferative DR (PDR) patients, 25 non-proliferative DR (NPDR) patients, 25 non-DR (NDR) patients, and 26 nondiabetic patients with idiopathic epiretinal membranes (ERMs, control). The protein level and mRNA expression level of GLP-1R were quantified by immunoblot and qRT-PCR and the levels of SGLT1, SGLT2, GLUT1, and GLUT2 expression were determined by PCR. Their association with clinical parameters and PBMCs/vitreous cytokine was analyzed. Furthermore, immunofluorescence staining of GLP-1R and SGLT2 was carried out on samples of fibrovascular membranes (FVMs) retrieved from 26 patients with PDR and 26 patients with ERMs.

Results

The transcriptional levels of GLP-1R and SGLT2 in PBMCs were significantly more decreased in PDR patients than in patients without DR and controls, which was simultaneously associated with an increased level of expression of tumor necrosis factor (TNF)-α and interferon (IFN)-γ. The expression levels of GLUT1 and GLUT2 were tightly correlated with their SGLT partners, respectively. Further, Immunofluorescence staining showed no positive staining of GLP-1R and SGLT2 was detected in the FVMs from PDR.

Conclusions

GLP-1R and SGLT2 were significantly decreased in PDR patients which was associated with an increased level of expression of TNF-α and IFN-γ. These findings implicate that defective GLP-1R and SGLT2 signaling may potentially correlate with immune response cytokines in patients with PDR.
Targeting pancreatic beta cell death in type 2 diabetes by polyphenols
Authors: García-Aguilar Ana , Guillén Carlos
Published: November 2022

Diabetes is a very complex disease which is characterized by the appearance of insulin resistance that is primarily compensated by an increase in pancreatic beta cell mass, generating hyperinsulinemia. After time, pancreatic beta cells die by apoptosis appearing in the second phase of the disease, and characterized by hypoinsulinemia. There are multiple conditions that can alter pancreatic beta cell homeostasis and viability, being the most relevant ones; ER stress, cytotoxicity by amylin, mTORC1 hyperactivity, oxidative stress, mitochondrial dysfunction, inflammation and alterations in autophagy/mitophagy flux. In addition, the possible effects that different polyphenols could exert in the modulation of these mechanisms and regulating pancreatic beta cell viability are analyzed. It is necessary a profound analysis and understanding of all the possible mechanisms involved in the control and maintenance of pancreatic beta cell viability to develop more accurate and target treatments for controlling beta cell homeostasis and preventing or even reversing type 2 diabetes mellitus.
Effect of chronic traffic noise on behavior and physiology of plateau pikas (Ochotona curzoniae)
Authors: Qu Jiapeng , Wang Yun , Kong Yaping , Zhu Hongjuan , Yu Yibo , Zhong Liang
Published: November 2022

During the last two decades, numerous studies have shown the effects of traffic noise on animal vocal communication. However, studies on the influences of traffic noise on wildlife behavior and physiology are scarce. In the present study, we experimentally manipulated the traffic noise exposure of plateau pika, a native small mammal widely distributed in the alpine meadow of Qinghai-Tibet Plateau, to explore the effects of traffic noise exposure on its behavior and physiology. We showed that noise exposure increased the pika’s exploration and cortisol concentration (CORT) but decreased the resting metabolic rate (RMR). In addition, the relationships between RMR and exploration or CORT appeared under traffic noise treatment. This study suggests that traffic noise plays a large role in the behavior and physiology of plateau pikas and may have a long-term negative effect on the fitness of rodent populations. Generalizing these non-lethal effects to different taxa is crucial for the conservation and management of biodiversity in this increasingly noisy world.
Genetically supported causality between benign prostate hyperplasia and urinary bladder neoplasms: A mendelian randomization study
Authors: Du Wenzhi , Wang Tianyi , Zhang Wenxiu , Xiao Yu , Wang Xinghuan
Published: November 2022

Background: Observational studies have suggested a possible association between benign prostate hyperplasia (BPH) and bladder cancer (BLCA). However, these studies are prone to errors and limitations or confounding factors, making them unsuitable for assessing the causal relationship between BPH and BLCA.

Objective: Two-sample Mendelian randomization (MR) was performed to determine a possible association between genetically predicted BPH and the risk of BLCA.

Methods: A two-sample MR analysis was performed utilizing the Integrative Epidemiology Unit genome-wide association (GWAS) database of the Medical Research Council, United Kingdom A series of control steps, including five primary methods, were performed to identify the most suitable instrumental variables (IVs) for MR analysis. Sensitivity analysis was conducted to avoid statistical errors, including heterogeneity and pleiotropic bias.

Results: Genetic variants associated with BPH (P < 5 × 10–8) and BLCA (P < 5 × 10–6) were identified as instrumental variables and assessed using GWAS summary data (BPH, 4,670 cases vs. 458,340 controls; BLCA, 1,279 cases vs. 372,016 controls). BPH exhibited a positive effect on the occurrence of BLCA (inverse variance weighted (IVW), odds ratio (OR) = 1.095, 95% confidence interval (CI) = 1.030–1.165, p = 0.003), but there was no causal effect for BLCA on BPH (IVW, OR = 1.092, 95% CI = 0.814–1.465, p = 0.554).

Conclusion: Genetically predicted BPH was associated with a higher risk of BLCA in all histological subtypes. In contrast, the evidence was not significant to back the causality of genetically induced BLCA on BPH. These findings indicate that BPH plays a key role in developing BLCA in the European population. Further studies are needed to uncover the underlying mechanisms.
RNA interference analysis of potential functions of cyclin A in the reproductive development of male oriental river prawns (Macrobrachium nipponense)
Authors: Zhang Wenyi , Xiong Yiwei , Wang Pengchao , Chen Tianyong , Jiang Sufei , Qiao Hui , Gong Yongsheng , Wu Yan , Jin Shubo , Fu Hongtuo
Published: November 2022

Cyclin A (CycA) plays essential roles in regulating multiple steps of the cell cycle, and it affects gonad development in mammals and invertebrates. Previous RNA interference (RNAi) analysis revealed that knocking-down the expression of CycA in female oriental river prawns (Macrobrachium nipponense) inhibited ovarian development. CycA was also predicted to have regulatory roles in reproductive development of male M. nipponense based on significant changes of Mn-CycA expression after eyestalk ablation. The goal of this study was to investigate the potential functions of CycA in the reproductive development of male M. nipponense using RNAi and histological observations. Quantitative real-time PCR analysis revealed that both single-side and double-side eyestalk ablation stimulated the expressions of Mn-CycA, and the expression was higher in prawns with double-side eyestalk ablation (p < 0.05). Mn-CycA expression was significantly higher in the testis and androgenic gland during the reproductive season than during the non-reproductive season (p < 0.05). In the RNAi analysis, Mn-CycA expression significantly decreased after prawns were injected with dsCycA, and the expression of insulin-like androgenic gland hormone (Mn-IAG) also decreased as Mn-CycA expression decreased. This result indicated that CycA positively regulated the expression of IAG in M. nipponense. Histological observations revealed that the number of sperm decreased dramatically to <5% of the total cells in the testis of the dsCycA-treated group compared to that of control group on day 14, indicating that knockdown of Mn-CycA expression inhibited testis development by affecting the expression of Mn-IAG in M. nipponense. These results highlighted the functions of CycA in male reproductive development of M. nipponense, which can be applied to future studies of male reproduction in other crustacean species.
Construction of a mitochondrial dysfunction related signature of diagnosed model to obstructive sleep apnea
Authors: Liu Qian , Hao Tao , Li Lei , Huang Daqi , Lin Ze , Fang Yipeng , Wang Dong , Zhang Xin
Published: November 2022

Background: The molecular mechanisms underlying obstructive sleep apnea (OSA) and its comorbidities may involve mitochondrial dysfunction. However, very little is known about the relationships between mitochondrial dysfunction-related genes and OSA.

Methods: Mitochondrial dysfunction-related differentially expressed genes (DEGs) between OSA and control adipose tissue samples were identified using data from the Gene Expression Omnibus database and information on mitochondrial dysfunction-related genes from the GeneCards database. A mitochondrial dysfunction-related signature of diagnostic model was established using least absolute shrinkage and selection operator Cox regression and then verified. Additionally, consensus clustering algorithms were used to conduct an unsupervised cluster analysis. A protein–protein interaction network of the DEGs between the mitochondrial dysfunction-related clusters was constructed using STRING database and the hub genes were identified. Functional analyses, including Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA), were conducted to explore the mechanisms involved in mitochondrial dysfunction in OSA. Immune cell infiltration analyses were conducted using CIBERSORT and single-sample GSEA (ssGSEA).

Results: we established mitochondrial dysfunction related four-gene signature of diagnostic model consisted of NPR3, PDIA3, SLPI, ERAP2, and which could easily distinguish between OSA patients and controls. In addition, based on mitochondrial dysfunction-related gene expression, we identified two clusters among all the samples and three clusters among the OSA samples. A total of 10 hub genes were selected from the PPI network of DEGs between the two mitochondrial dysfunction-related clusters. There were correlations between the 10 hub genes and the 4 diagnostic genes. Enrichment analyses suggested that autophagy, inflammation pathways, and immune pathways are crucial in mitochondrial dysfunction in OSA. Plasma cells and M0 and M1 macrophages were significantly different between the OSA and control samples, while several immune cell types, especially T cells (γ/δ T cells, natural killer T cells, regulatory T cells, and type 17 T helper cells), were significantly different among mitochondrial dysfunction-related clusters of OSA samples.

Conclusion: A novel mitochondrial dysfunction-related four-gen signature of diagnostic model was built. The genes are potential biomarkers for OSA and may play important roles in the development of OSA complications.
The immunosuppressive microenvironment and immunotherapy in human glioblastoma
Authors: Zhang Xuehua , Zhao Leilei , Zhang He , Zhang Yurui , Ju Huanyu , Wang Xiaoyu , Ren Huan , Zhu Xiao , Dong Yucui
Published: November 2022

Glioblastoma multiforme (GBM) is the most malignant intracranial tumor in adults, characterized by extensive infiltrative growth, high vascularization, and resistance to multiple therapeutic approaches. Among the many factors affecting the therapeutic effect, the immunosuppressive GBM microenvironment that is created by cells and associated molecules via complex mechanisms plays a particularly important role in facilitating evasion of the tumor from the immune response. Accumulating evidence is also revealing a close association of the gut microbiota with the challenges in the treatment of GBM. The gut microbiota establishes a connection with the central nervous system through bidirectional signals of the gut–brain axis, thus affecting the occurrence and development of GBM. In this review, we discuss the key immunosuppressive components in the tumor microenvironment, along with the regulatory mechanism of the gut microbiota involved in immunity and metabolism in the GBM microenvironment. Lastly, we concentrate on the immunotherapeutic strategies currently under investigation, which hold promise to overcome the hurdles of the immunosuppressive tumor microenvironment and improve the therapeutic outcome for patients with GBM.
Memory-like innate lymphoid cells in the pathogenesis of asthma
Authors: Ham Jongho , Lim MinYeong , Kim Dongmo , Kim Hye Young
Published: November 2022

Innate lymphoid cells (ILCs) are recently discovered innate immune cells that reside and self-renew in mucosal tissues and serve as the first line of defense against various external insults. They include natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer cells. The development and functions of ILC1–3 reflect those of their adaptive immunity TH1, TH2, and TH17 T-cell counterparts. Asthma is a heterogeneous disease caused by repeated exposure to specific allergens or host/environmental factors (e.g., obesity) that stimulate pathogenic pulmonary immune cells, including ILCs. Memory used to be a hallmark of adaptive immune cells until recent studies of monocytes, macrophages, and NK cells showed that innate immune cells can also exhibit greater responses to re-stimulation and that these more responsive cells can be long-lived. Besides, a series of studies suggest that the tissue-resident innate lymphoid cells have memory-like phenotypes, such as increased cytokine productions or epigenetic modifications following repetitive exposure to allergens. Notably, both clinical and mouse studies of asthma show that various allergens can generate memory-like features in ILC2s. Here, we discuss the biology of ILCs, their roles in asthma pathogenesis, and the evidence supporting ILC memory. We also show evidence suggesting memory ILCs could help drive the phenotypic heterogeneity in asthma. Thus, further research on memory ILCs may be fruitful in terms of developing new therapies for asthma.
Combined bulk RNA-seq and single-cell RNA-seq identifies a necroptosis-related prognostic signature associated with inhibitory immune microenvironment in glioma
Authors: Wan Sicheng , Moure Ulrich Aymard Ekomi , Liu Ruochen , Liu Chaolong , Wang Kun , Deng Longfei , Liang Ping , Cui Hongjuan
Published: November 2022

Necroptosis is a programmed cell death playing a significant role in cancer. Although necroptosis has been related to tumor immune environment (TIME) remodeling and cancer prognosis, however, the role of necroptosis-related genes (NRGs) in glioma is still elusive. In this study, a total of 159 NRGs were obtained, and parameters such as mutation rate, copy number variation (CNV), and relative expression level were assessed. Then, we constructed an 18-NRGs-based necroptosis-related signature (NRS) in the TCGA dataset, which could predict the patient’s prognosis and was validated in two external CGGA datasets. We also explored the correlation between NRS and glioma TIME, chemotherapy sensitivity, and certain immunotherapy-related factors. The two necroptosis-related subtypes were discovered and could also distinguish the patients' prognosis. Through the glioblastoma (GBM) scRNA-seq data analysis, NRGs’ expression levels in different GBM patient tissue cell subsets were investigated and the relative necroptosis status of different cell subsets was assessed, with the microglia score culminating among all. Moreover, we found a high infiltration level of immunosuppressive cells in glioma TIME, which was associated with poor prognosis in the high-NRS glioma patient group. Finally, the necroptosis suppressor CASP8 exhibited a high expression in glioma and was associated with poor prognosis. Subsequent experiments were performed in human glioma cell lines and patients' tissue specimens to verify the bioinformatic analytic findings about CASP8. Altogether, this study provides comprehensive evidence revealing a prognostic value of NRGs in glioma, which is associated with TIME regulation.
The effect of organ-specific tumor microenvironments on response patterns to immunotherapy
Authors: Conway Jordan W. , Braden Jorja , Wilmott James S. , Scolyer Richard A. , Long Georgina V. , Pires da Silva Inês
Published: November 2022

Immunotherapy, particularly immune checkpoint inhibitors, have become widely used in various settings across many different cancer types in recent years. Whilst patients are often treated on the basis of the primary cancer type and clinical stage, recent studies have highlighted disparity in response to immune checkpoint inhibitors at different sites of metastasis, and their impact on overall response and survival. Studies exploring the tumor immune microenvironment at different organ sites have provided insights into the immune-related mechanisms behind organ-specific patterns of response to immunotherapy. In this review, we aimed to highlight the key learnings from clinical studies across various cancers including melanoma, lung cancer, renal cell carcinoma, colorectal cancer, breast cancer and others, assessing the association of site of metastasis and response to immune checkpoint inhibitors. We also summarize the key clinical and pre-clinical findings from studies exploring the immune microenvironment of specific sites of metastasis. Ultimately, further characterization of the tumor immune microenvironment at different metastatic sites, and understanding the biological drivers of these differences, may identify organ-specific mechanisms of resistance, which will lead to more personalized treatment approaches for patients with innate or acquired resistance to immunotherapy.
In silico and in vitro arboviral MHC class I-restricted-epitope signatures reveal immunodominance and poor overlapping patterns
Authors: Lopes-Ribeiro Ágata , Araujo Franklin Pereira , Oliveira Patrícia de Melo , Teixeira Lorena de Almeida , Ferreira Geovane Marques , Lourenço Alice Aparecida , Dias Laura Cardoso Corrêa , Teixeira Caio Wilker , Retes Henrique Morais , Lopes Élisson Nogueira , Versiani Alice Freitas , Barbosa-Stancioli Edel Figueiredo , da Fonseca Flávio Guimarães , Martins-Filho Olindo Assis , Tsuji Moriya , Peruhype-Magalhães Vanessa , Coelho-dos-Reis Jordana Grazziela Alves
Published: November 2022

Introduction

The present work sought to identify MHC-I-restricted peptide signatures for arbovirus using in silico and in vitro peptide microarray tools.

Methods

First, an in-silico analysis of immunogenic epitopes restricted to four of the most prevalent human MHC class-I was performed by identification of MHC affinity score. For that, more than 10,000 peptide sequences from 5 Arbovirus and 8 different viral serotypes, namely Zika (ZIKV), Dengue (DENV serotypes 1-4), Chikungunya (CHIKV), Mayaro (MAYV) and Oropouche (OROV) viruses, in addition to YFV were analyzed. Haplotype HLA-A*02.01 was the dominant human MHC for all arboviruses. Over one thousand HLA-A2 immunogenic peptides were employed to build a comprehensive identity matrix. Intending to assess HLAA*02:01 reactivity of peptides in vitro, a peptide microarray was designed and generated using a dimeric protein containing HLA-A*02:01.

Results

The comprehensive identity matrix allowed the identification of only three overlapping peptides between two or more flavivirus sequences, suggesting poor overlapping of virus-specific immunogenic peptides amongst arborviruses. Global analysis of the fluorescence intensity for peptide-HLA-A*02:01 binding indicated a dose-dependent effect in the array. Considering all assessed arboviruses, the number of DENV-derived peptides with HLA-A*02:01 reactivity was the highest. Furthermore, a lower number of YFV-17DD overlapping peptides presented reactivity when compared to non-overlapping peptides. In addition, the assessment of HLA-A*02:01-reactive peptides across virus polyproteins highlighted non-structural proteins as “hot-spots”. Data analysis supported these findings showing the presence of major hydrophobic sites in the final segment of non-structural protein 1 throughout 2a (Ns2a) and in nonstructural proteins 2b (Ns2b), 4a (Ns4a) and 4b (Ns4b).

Discussion

To our knowledge, these results provide the most comprehensive and detailed snapshot of the immunodominant peptide signature for arbovirus with MHC-class I restriction, which may bring insight into the design of future virus-specific vaccines to arboviruses and for vaccination protocols in highly endemic areas.
What do animal models tell us about the role of EBV in the pathogenesis of multiple sclerosis?
Authors: Hassani Asma , Khan Gulfaraz
Published: November 2022

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS), marked primarily by demyelination, inflammation, and neurodegeneration. While the prevalence and incidence rates of MS are on the rise, the etiology of the disease remains enigmatic. Nevertheless, it is widely acknowledged that MS develops in persons who are both genetically predisposed and exposed to a certain set of environmental factors. One of the most plausible environmental culprits is Epstein-Barr virus (EBV), a common herpesvirus asymptomatically carried by more than 90% of the adult population. How EBV induces MS pathogenesis remains unknown. A comprehensive understanding of the biology of EBV infection and how it contributes to dysfunction of the immune system and CNS, requires an appreciation of the viral dynamics within the host. Here, we aim to outline the different animal models, including nonhuman primates (NHP), rodents, and rabbits, that have been used to elucidate the link between EBV and MS. This review particularly focuses on how the disruption in virus-immune interaction plays a role in viral pathogenesis and promotes neuroinflammation. We also summarize the effects of virus titers, age of animals, and route of inoculation on the neuroinvasiveness and neuropathogenic potential of the virus. Reviewing the rich data generated from these animal models could provide directions for future studies aimed to understand the mechanism(s) by which EBV induces MS pathology and insights for the development of prophylactic and therapeutic interventions that could ameliorate the disease.
Response of immunoglobulin M in gut mucosal immunity of common carp (Cyprinus carpio) infected with Aeromonas hydrophila
Authors: Mu Qingjiang , Dong Zhaoran , Kong Weiguang , Wang Xinyou , Yu Jiaqian , Ji Wei , Su Jianguo , Xu Zhen
Published: November 2022

Immunoglobulin (Ig) M is an important immune effector that protects organisms from a wide variety of pathogens. However, little is known about the immune response of gut mucosal IgM during bacterial invasion. Here, we generated polyclonal antibodies against common carp IgM and developed a model of carp infection with Aeromonas hydrophila via intraperitoneal injection. Our findings indicated that both innate and adaptive immune responses were effectively elicited after A. hydrophila infection. Upon bacterial infection, IgM+ B cells were strongly induced in the gut and head kidney, and bacteria-specific IgM responses were detected in high levels both in the gut mucus and serum. Moreover, our results suggested that IgM responses may vary in different infection strategies. Overall, our findings revealed that the infected common carp exhibited high resistance to this representative enteropathogenic bacterium upon reinfection, suggesting that IgM plays a key role in the defense mechanisms of the gut against bacterial invasion. Significantly, the second injection of A. hydrophila induces strong local mucosal immunity in the gut, which is essential for protection against intestinal pathogens, providing reasonable insights for vaccine preparation.
Age-dependent NK cell dysfunctions in severe COVID-19 patients
Authors: Fionda Cinzia , Ruggeri Silvia , Sciumè Giuseppe , Laffranchi Mattia , Quinti Isabella , Milito Cinzia , Palange Paolo , Menichini Ilaria , Sozzani Silvano , Frati Luigi , Gismondi Angela , Santoni Angela , Stabile Helena
Published: November 2022

Natural Killer (NK) cells are key innate effectors of antiviral immune response, and their activity changes in ageing and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we investigated the age-related changes of NK cell phenotype and function during SARS-CoV-2 infection, by comparing adult and elderly patients both requiring mechanical ventilation. Adult patients had a reduced number of total NK cells, while elderly showed a peculiar skewing of NK cell subsets towards the CD56lowCD16high and CD56neg phenotypes, expressing activation markers and check-point inhibitory receptors. Although NK cell degranulation ability is significantly compromised in both cohorts, IFN-γ production is impaired only in adult patients in a TGF-β−dependent manner. This inhibitory effect was associated with a shorter hospitalization time of adult patients suggesting a role for TGF-β in preventing an excessive NK cell activation and systemic inflammation. Our data highlight an age-dependent role of NK cells in shaping SARS-CoV-2 infection toward a pathophysiological evolution.
Multiple CAR-T cell therapy for acute B-cell lymphoblastic leukemia after hematopoietic stem cell transplantation: A case report
Authors: Deng Lei , Xiaolin Yu , Wu Qian , Song Xiaochen , Li Wenjun , Hou Yixi , Liu Yue , Wang Jing , Tian Jun , Zuo Xiaona , Zhou Fang
Published: November 2022

B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy. The cure rate has reached 90% after conventional chemotherapy and hematopoietic stem cell transplantation (HSCT), but the prognosis of patients with relapsed and refractory (R/R) leukemia is still poor after conventional treatment. Since FDA approved CD19 CAR-T cell (Kymriah) for the treatment of R/R B-ALL, increasing studies have been conducted on CAR-T cells for R/R ALL. Herein, we report the treatment of a patient with ALL who relapsed after allogeneic HSCT, had a complete remission (CR) to murine scFv CD19 CAR-T but relapsed 15 months later. Partial response was achieved after humanized CD19 CAR-T treatment, and the patient finally achieved disease-free survival after sequential CD22 CAR-T treatment. By comparing the treatment results of different CAR-T cells in the same patient, this case suggests that multiple CAR-T therapies are effective and safe in intramedullary and extramedullary recurrence in the same patient, and the expansion of CAR-T cells and the release of inflammatory cytokines are positively correlated with their efficacy. However, further clinical studies with large sample sizes are still needed for further clarification.
Circular RNA hsa_circ_0007990 as a blood biomarker for unruptured intracranial aneurysm with aneurysm wall enhancement
Authors: Wu Xiao-Bing , Wu You-Tao , Guo Xin-Xing , Xiang Chun , Chen Pei-Sheng , Qin Wang , Shi Zhong-Song
Published: November 2022

Background

Circular RNAs (circRNAs) may involve the formation and rupture of intracranial aneurysms (IA). Inflammation plays a vital role in the development and progression of IA, which can be reflected by aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI). This study aims to evaluate the role of circRNAs as the blood inflammatory biomarker for unruptured IA (UIA) patients with AWE on HR-VWI.

Methods

We analyzed the circRNA expression profiles in the peripheral blood samples among subjects from saccular UIA with AWE, UIA without AWE, and healthy controls by the circRNA microarray. The differential expression of hsa_circ_0007990 was assessed. We constructed the hsa_circ_0007990-microRNA-mRNA network and the regulatory axis of hub genes associated with the AWE in UIA.

Results

Eighteen patients harboring saccular UIAs with HR VWI and five healthy controls were included. We found 412 differentially expressed circRNAs between UIA patients and healthy controls by circRNA microarray. Two hundred thirty-one circRNAs were significantly differentially expressed in UIA patients with AWE compared with those without AWE. Twelve upregulated circRNAs were associated with AWE of UIA, including hsa_circ_0007990, hsa_circ_0114507, hsa_circ_0020460, hsa_circ_0053944, hsa_circ_0000758, hsa_circ_0000034, hsa_circ_0009127, hsa_circ_0052793, hsa_circ_0000301 and hsa_circ_0000729. The expression of hsa_circ_0007990 was increased gradually in the healthy control, UIA without AWE, and UIA with AWE confirmed by RT-PCR (P<0.001). We predicted 4 RNA binding proteins (Ago2, DGCR8, EIF4A3, PTB) and period circadian regulator 1 as an encoding protein with hsa_circ_0007990. The hsa_circ_0007990-microRNA-mRNA network containing five microRNAs (miR-4717-5p, miR-1275, miR-150-3p, miR-18a-5p, miR-18b-5p), and 97 mRNAs was constructed. The five hub genes (hypoxia-inducible factor 1 subunit alpha, estrogen receptor 1, forkhead box O1, insulin-like growth factor 1, CREB binding protein) were involved in the inflammatory response.

Conclusion

Differentially expressed blood circRNAs associated with AWE on HR-VWI may be the novel inflammatory biomarkers for assessing UIA patients. The mechanism of hsa_circRNA_0007990 for UIA progression needs to investigate further.