bluuebunny/crossref_metadata_2025 huggingface dataset:
Seabuckthorn polysaccharide combined with astragalus polysaccharide ameliorate alcoholic fatty liver by regulating intestinal flora
Authors: Liu Jiayue , Kong Lingzhou , Shao Mengting , Sun Changhai , Li Changxu , Wang Yanyan , Chai Xue , Wang Yuliang , Zhang Yu , Li Xiaoliang , Zhao Hong
Published: September 2022

Background

At present, the incidence of alcoholic fatty liver disease (AFLD) is increasing year by year, and numerous studies have confirmed that liver diseases are closely related to intestinal flora. Seabuckthorn and Astragalus membranaceus, as traditional Chinese medicine (TCM) with the homology of medicine and food, have good liver protection, and their polysaccharides can regulate the intestinal flora. Here, we studied the effects of HRP, APS and the combination of the two polysaccharides on the intestinal flora of AFLD mice, which provided scientific basis for the treatment of AFLD with the two polysaccharides.

Materials and methods

Thirty Kunming (KM) mice were randomly divided into the control group (Con), the model group (Mod), the HRP treatment group (HRP), the APS treatment group (APS), and HRP+APS treatment group (HRP+APS), with six mice in each group. The AFLD model was constructed by continuous intragastric administration of 42% vol Niulanshan ethanol solution for 28 days, and the mice in each polysaccharide group were given corresponding drugs. The levels of AST, ALT, TC and TG in serum of mice were measured. 16S rRNA amplicon sequencing technique was used to determine the diversity and richness of intestinal flora, and the relative abundance of intestinal flora at phylum level and genus level of the mice in each group.

Results

HRP, APS and HRP+APS could reduce the serum levels of AST, ALT, TC and TG in mice. In addition, HRP, APS and HRP + APS restored the diversity, relative abundance and community structure of intestinal mucosa bacteria in AFLD mice to a certain extent. Specifically, HRP, APS and HRP+APS remarkably decreased the ratio of Firmicutes to Bacteroidetes, and ultimately increased the abundance of beneficial bacteria and reduced the abundance of pathogenic bacteria.

Conclusion

HRP, APS, and HRP+APS can improve the intestinal microecology of AFLD model mice, alleviate liver injury, and maintain normal intestinal function in different degrees.
Identification of hub genes for early detection of bone metastasis in breast cancer
Authors: Zhao Zitong , Yang Haoran , Ji Guangling , Su Shanshan , Fan Yuqi , Wang Minghao , Gu Shengli
Published: September 2022

Background

Globally, among all women, the most frequently detected and diagnosed and the most lethal type of cancer is breast cancer (BC). In particular, bone is one of the most frequent distant metastases 24in breast cancer patients and bone metastasis arises in approximately 80% of advanced patients. Thus, we need to identify and validate early detection markers that can differentiate metastasis from non-metastasis breast cancers.

Methods

GSE55715, GSE103357, and GSE146661 gene expression profiling data were downloaded from the GEO database. There was 14 breast cancer with bone metastasis samples and 8 breast cancer tissue samples. GEO2R was used to screen for differentially expressed genes (DEGs). The volcano plots, Venn diagrams, and annular heatmap were generated by using the ggplot2 package. By using the cluster Profiler R package, KEGG and GO enrichment analyses of DEGs were conducted. Through PPI network construction using the STRING database, key hub genes were identified by cytoHubba. Finally, K-M survival and ROC curves were generated to validate hub gene expression.

Results

By GO enrichment analysis, 143 DEGs were enriched in the following GO terms: extracellular structure organization, extracellular matrix organization, leukocyte migration class II protein complex, collagen tridermic protein complex, extracellular matrix structural constituent, growth factor binding, and platelet-derived growth factor binding. In the KEGG pathway enrichment analysis, DEGs were enriched in Staphylococcus aureus infection, Complement and coagulation cascades, and Asthma. By PPI network analysis, we selected the top 10 genes, including SLCO2B1, STAB1, SERPING1, HLA-DOA, AIF1, GIMAP4, C1orf162, HLA-DMB, ADAP2, and HAVCR2. By using TCGA and THPA databases, we validated 2 genes, SERPING1 and GIMAP4, that were related to the early detection of bone metastasis in BC.

Conclusions

2 abnormally expressed hub genes could play a pivotal role in the breast cancer with bone metastasis by affecting bone homeostasis imbalance in the bone microenvironment.
Mechanism of negative modulation of FSH signaling by salt-inducible kinases in rat granulosa cells
Authors: Armouti Marah , Rodriguez-Esquivel Miriam , Stocco Carlos
Published: September 2022

The optimal development of preovulatory follicles needs follicle-stimulating hormone (FSH). Recent findings revealed that salt-inducible kinases (SIKs) inhibit FSH actions in humans and rodents. This report seeks to increase our understanding of the molecular mechanisms controlled by SIKs that participate in the inhibition of FSH actions in primary rat granulosa cells (GCs). The results showed that FSH causes a transient induction of Sik1 mRNA. In contrast, SIK inhibition had no effects on FSH receptor expression. Next, we determined whether SIK inhibition enhances the effect of several sequential direct activators of the FSH signaling pathway. The findings revealed that SIK inhibition stimulates the induction of steroidogenic genes by forskolin, cAMP, protein kinase A (PKA), and cAMP-response element-binding protein (CREB). Strikingly, FSH stimulation of CREB and AKT phosphorylation was not affected by SIK inhibition. Therefore, we analyzed the expression and activation of putative CREB cofactors and demonstrated that GCs express CREB-regulated transcriptional coactivators (CRTC2) and that FSH treatment and SIK inhibition increase the nuclear expression of this factor. We concluded that SIKs target the FSH pathway by affecting factors located between cAMP/PKA and CREB and propose that SIKs control the activity of CRTC2 in ovarian GCs. The findings demonstrate for the first time that SIKs blunt the response of GCs to FSH, cAMP, PKA, and CREB, providing further evidence for a crucial role for SIKs in regulating ovarian function and female fertility.
Artificial intelligence promotes the diagnosis and screening of diabetic retinopathy
Authors: Huang Xuan , Wang Hui , She Chongyang , Feng Jing , Liu Xuhui , Hu Xiaofeng , Chen Li , Tao Yong
Published: September 2022

Deep learning evolves into a new form of machine learning technology that is classified under artificial intelligence (AI), which has substantial potential for large-scale healthcare screening and may allow the determination of the most appropriate specific treatment for individual patients. Recent developments in diagnostic technologies facilitated studies on retinal conditions and ocular disease in metabolism and endocrinology. Globally, diabetic retinopathy (DR) is regarded as a major cause of vision loss. Deep learning systems are effective and accurate in the detection of DR from digital fundus photographs or optical coherence tomography. Thus, using AI techniques, systems with high accuracy and efficiency can be developed for diagnosing and screening DR at an early stage and without the resources that are only accessible in special clinics. Deep learning enables early diagnosis with high specificity and sensitivity, which makes decisions based on minimally handcrafted features paving the way for personalized DR progression real-time monitoring and in-time ophthalmic or endocrine therapies. This review will discuss cutting-edge AI algorithms, the automated detecting systems of DR stage grading and feature segmentation, the prediction of DR outcomes and therapeutics, and the ophthalmic indications of other systemic diseases revealed by AI.
Recognition of fold- and function-specific sites in the ligand-binding domain of the thyroid hormone receptor-like family
Authors: Verma Sonia , Chakraborti Soumyananda , Singh Om P. , Pande Veena , Dixit Rajnikant , Pandey Amit V. , Pandey Kailash C.
Published: September 2022

Background

The thyroid hormone receptor-like (THR-like) family is the largest transcription factors family belonging to the nuclear receptor superfamily, which directly binds to DNA and regulates the gene expression and thereby controls various metabolic processes in a ligand-dependent manner. The THR-like family contains receptors THRs, RARs, VDR, PPARs, RORs, Rev-erbs, CAR, PXR, LXRs, and others. THR-like receptors are involved in many aspects of human health, including development, metabolism and homeostasis. Therefore, it is considered an important therapeutic target for various diseases such as osteoporosis, rickets, diabetes, etc.

Methods

In this study, we have performed an extensive sequence and structure analysis of the ligand-binding domain (LBD) of the THR-like family spanning multiple taxa. We have use different computational tools (information-theoretic measures; relative entropy) to predict the key residues responsible for fold and functional specificity in the LBD of the THR-like family. The MSA of THR-like LBDs was further used as input in conservation studies and phylogenetic clustering studies.

Results

Phylogenetic analysis of the LBD domain of THR-like proteins resulted in the clustering of eight subfamilies based on their sequence homology. The conservation analysis by relative entropy (RE) revealed that structurally important residues are conserved throughout the LBDs in the THR-like family. The multi-harmony conservation analysis further predicted specificity in determining residues in LBDs of THR-like subfamilies. Finally, fold and functional specificity determining residues (residues critical for ligand, DBD and coregulators binding) were mapped on the three-dimensional structure of thyroid hormone receptor protein. We then compiled a list of natural mutations in THR-like LBDs and mapped them along with fold and function-specific mutations. Some of the mutations were found to have a link with severe diseases like hypothyroidism, rickets, obesity, lipodystrophy, epilepsy, etc.

Conclusion

Our study identifies fold and function-specific residues in THR-like LBDs. We believe that this study will be useful in exploring the role of these residues in the binding of different drugs, ligands, and protein-protein interaction among partner proteins. So this study might be helpful in the rational design of either ligands or receptors.
Proximity ligation assay to study TSH receptor homodimerization and crosstalk with IGF-1 receptors in human thyroid cells
Authors: Krieger Christine C. , Boutin Alisa , Neumann Susanne , Gershengorn Marvin C.
Published: September 2022

Proximity ligation assay (PLA) is a methodology that permits detection of protein-protein closeness, that is, proteins that are within 40 nanometers of each other, in cells or tissues at endogenous protein levels or after exogenous overexpression. It detects the protein(s) with high sensitivity and specificity because it employs a DNA hybridization step followed by DNA amplification. PLA has been used successfully with many types of proteins. In this methods paper, we will describe the workings of PLA and provide examples of its use to study TSH/IGF-1 receptor crosstalk in Graves’ orbital fibroblasts (GOFs) and TSH receptor homodimerization in primary cultures of human thyrocytes.
Optimal scheduling of multi-microgrids with power to hydrogen considering federated demand response
Authors: Hu Qinran , Zhou Yufeng , Ding Haohui , Qin Panhao , Long Yu
Published: September 2022

Hydrogen is regarded as a promising fuel in the transition to clean energy. Nevertheless, as the demand for hydrogen increases, some microgrids equipped with P2H (MGH) will encounter the issue of primary energy deficiency. Meanwhile, some microgrids (MGs) face the difficulty of being unable to consume surplus energy locally. Hence, we interconnect MGs with different energy characteristics and then establish a collaborative scheduling model of multi-microgrids (MMGs). In this model, a federated demand response (FDR) program considering predictive mean voting is designed to coordinate controllable loads of electricity, heat, and hydrogen in different MGs. With the coordination of FDR, the users’ satisfaction and comfort in each MG are kept within an acceptable range. To further adapt to an actual working condition of the microturbine (MT) in MGH, a power interaction method is proposed to maintain the operating power of the MT at the optimum load level and shave peak and shorten the operating periods of MT. In the solution process, the sequence operation theory is utilized to deal with the probability density of renewable energy. A series of case studies on a test system of MMG demonstrate the effectiveness of the proposed method.
Newtonian heating effect in pulsating magnetohydrodynamic nanofluid flow through a constricted channel: A numerical study
Authors: Ali Amjad , Bukhari Zainab , Amjad Muhammad , Ahmad Sohail , Tag El. Din El. Sayed M. , Hussain Syed M.
Published: September 2022

This article investigates the pulsatile flow of viscous incompressible MHD nanofluid in a rectangular channel. At the upper and lower walls, the channel has symmetrical constrictions. The goal is to analyze the heat transfer features of the nanofluid flow under the effect of the magnetic field and thermal radiation. Five different nanofluids, formed with nanoparticles of copper (Cu), magnetite (Fe3O4), silver (Ag), titanium oxide (TiO2), and single wall carbon nanotube (SWCNT) in the base fluid of water, are considered in the study. The unsteady governing equations are transformed using the vorticity-stream function approach. The solution is obtained using the finite difference technique (FDM). The effect of various flow controlling parameters on velocity, temperature, Nusselt, and skin-friction profiles is inspected by using graphs. Across the channel, graphs of vorticity, streamlines, and temperature distribution are also displayed. The thickness of the thermal boundary layer upsurges with escalating values of the magnetic field, radiation parameters, and solid volume fraction, whereas it declines with escalating values of the Strouhal and Prandtl numbers. The profiles are usually found to have a more regular pattern upstream of the constriction than that downstream of the constriction. At the throat of the constriction, the carbon nanotube-based nanofluid attains higher temperatures than the other nanofluids downstream of the constriction. However, in the lee of the constriction, silver-based nanofluid attains higher temperatures than the other nanofluids downstream of the constriction. The behavior, in most cases, is opposite upstream of the constriction. The findings of the study can be utilized to cure stenosis in blood vessels, design biomechanical devices, and employ flow pulsation to control industrial operations.
A review of modeling and simulation tools for microgrids based on solar photovoltaics
Authors: Seane T. B. , Samikannu R. , Bader T.
Published: September 2022

Solar Photo Voltaic (PV) powered community microgrids are a promising sustainable solution for neighborhoods, residential quarters, and cities in sub-Saharan Africa (SSA) to meet their energy demands locally and to increase energy independence and resilience. This review provides a comprehensive study on the nature of solar PV community microgrids. Through their capacity to operate in both grid-connected and island modes, community microgrids improve utility system resiliency while also boosting energy security in local states and towns. The integration of solar PV microgrids with the electricity utility grid requires control strategies to facilitate the load sharing between distributed generation units, voltage and frequency control, as well as emergency islanding. Control strategies such as hierarchical control and droop are discussed in the review article. To identify the effectiveness of control strategies through system simulation, a review of various modeling designs of individual components in a solar PV microgrid system is discussed. The article goes on to talk about energy optimization approaches and their economic impact on microgrid systems. Finally, the review concludes with an overview of the technical challenges encountered in the integration of solar PV systems in microgrids.
TOD and vibrancy: The spatio-temporal impacts of the built environment on vibrancy
Authors: Yu Bingjie , Cui Xu , Li Hong , Luo Pinyang , Liu Runze , Yang Tian
Published: September 2022

Urban vibrancy is described by the activities of residents and their spatio-temporal dynamics. The metro station area (MSA) is one of the densest and most populous areas of the city. Thus, creating a vibrant and diverse urban environment becomes an important goal of transit-oriented development (TOD). Existing studies indicate that the built environment decisively determines MSA-level urban vibrancy. Meanwhile, the spatio-temporal heterogeneity of such effects requires thoroughly exploration and justification. In this study, we first apply mobile signaling data to quantify and decipher the spatio-temporal distribution characteristics of the MSA-level urban vibrancy in Chengdu, China. Then, we measure the built environment of the MSA by using multi-source big data. Finally, we employ geographically and temporally weighted regression (GTWR) models to examine the spatio-temporal non-stationarity of the impact of the MSA-level built environment on urban vibrancy. The results show that: 1) The high-vibrant MSAs concentrate in the commercial center and the employment center. 2) Indicators such as residential density, overpasses, road density, road network integration index, enterprise density, and restaurant density are significantly and positively associated with urban vibrancy, while indicators such as housing price and bus stop density are negatively associated with urban vibrancy. 3) The GTWR model better fits the data than the stepwise regression model. The impact of the MSA-level built environment on urban vibrancy shows a strong non-stationarity in both spatial and temporal dimensions, which matches with the spatio-temporal dynamic patterns of the residents’ daily work, leisure, and consumption activities. The findings can provide references for planners and city managers on how to frame vibrant TOD communities.
Sustainable corporate environmental information disclosure: Evidence for green recovery from polluting firms of China
Authors: Long Fengjiao , Chen Qin , Xu Lu , Wang Jian , Vasa László
Published: September 2022

For a greener society, good corporate environmental information disclosure is crucial. This study empirically examines the influence of media attention and state-owned equity, and their interaction on corporate environmental information disclosure by A-share heavily polluting firms in the Shanghai and Shenzhen stock markets from 2015 to 2019. The results show that state-owned equity can improve the level of corporate environmental information disclosure; however, it mainly affects financial environmental information disclosure. Media attention also improves the level of corporate environmental information disclosure, but only for non-financial environmental information. Moreover, media attention and state-owned equity have a certain substitution effect on environmental information disclosure: a higher state-owned equity ratio weakens the positive effect of media attention on environmental information disclosure. To improve environmental information disclosure, the government must clarify disclosure standards to improve the comparability of environmental information. In addition, media and shareholders can fully leverage their external and internal supervisory roles to promote the environmental responsibilities of firms. Our findings can be useful for further promoting corporate environmental information disclosure and developing relevant policies.
Integrated transcriptomic and metabolomic analyses of pak choi [Brassica pekinensis (Lour.) Rupr] response to combined stress of acid rain and cadmium-containing atmospheric fine particulate matter
Authors: Zha Yan , Zhao Bo , Qiu Jieren , Li Xuqing
Published: September 2022

Heavy metal-containing atmospheric particulate matter (PM) and acid rain (AR) trigger molecular alteration in plants, perturbing metabolites and damaging plant growth. However, the molecular mechanisms of plants under AR along with Cd-containing atmospheric fine particulate matter (PM2.5-Cd) stress remain unknown. In this study, integrated transcriptomics and metabolomics analyses of pak choi (Brassica pekinensis (Lour.) Rupr) exposed to AR (pH3.5) and PM2.5-Cd (500 μg·m−3) stress were performed. Metabolomics analyses revealed that AR-Cd stress mainly affected 42 metabolic pathways, including 451 differentially expressed metabolites (DEMs). RNA-seq identified 735 common differentially expressed genes (DEGs: 557 upregulated and 178 downregulated). Further analysis found several important DEGs (transcription factors, metabolic pathways genes, and signal transduction genes), including WRKY11, WRKY53, WRKY41, MYB73, NAC062, NAC046, HSFA4A, ABCC3, CAXs, GSTs, AZFs, PODs, PME41, CYP707A2, and CDPK32 implying that Cd chelate sequestration into the vacuoles, the antioxidant system, cell wall biosynthesis pathway, and calcium signaling play a critical role in AR damage and Cd detoxification. Conjoint revealed phenylpropanoid and flavonoid biosynthesis pathways with different metabolism patterns, including the key DEM, chlorogenic acids. The results obtained using multiple approaches provide a molecular-scale perspective on plant response to AR-Cd stress.
24 h movement behavior and metabolic syndrome study protocol: A prospective cohort study on lifestyle and risk of developing metabolic syndrome in undergraduate students from low-income regions during a pandemic
Authors: Nascimento-Ferreira Marcus Vinicius , Marin Kliver Antonio , Abrão Ferreira Ruhena Kelber , Oliveira Luiz Fernando , Bandeira Ana Caroline , Silva Sousa Paula , Miranda de Sousa Josilene , de Almeida Cardoso Antonio Gibran , Conceição da Silva Lorrane Cristine , Rosa Ana Clara Arrais , de Carvalho Millena Vaz , Pereira de Carvalho Silva Ithamara Sthefanny , Franco Alaiana Marinho , Torres-Leal Francisco Leonardo , Barbosa de Carvalho Heráclito , Ferreira de Moraes Augusto César
Published: September 2022

Introduction

Obesity and its comorbidities are increasingly prevalent in Latin America, with a more rapid growth in individuals with lower income. The composition of movement behaviors within a 24 h period may have important implications for obesity, metabolic and mental health in cross-sectional data. However, a longitudinal study is needed to confirm the findings from the primarily cross-sectional evidence. The COVID-19 pandemic has been associated with cardiometabolic outcomes and has impeded healthy behavior.

Objectives

The first objective is to evaluate the time elapsed since the diagnosis of not meeting 24 h movement guidelines and the potential subsequent onset of metabolic syndrome in undergraduate students from low-income regions within 4 years of follow up. The second objective is to test the association between 24 h movement, mental wellbeing, eating behaviors, and abdominal obesity in the period of this pandemic.

Methods

The 24 h movement behavior and metabolic syndrome (24 h-MESYN) study is a multicentre cohort study that will include participants from two Brazilian cities within the 2022–2025 period to asses the first objective, and also a nested case-control study at the baseline will be carried out to evaluate the second objective. Previously, we conducted a feasibility study in the academic year of 2021 to assessing the psychometric properties of subjective tools, refine our study protocol, and adjust the epidemiological conditions of the cohort's subsequent phases (like as prevalence of exposure of interest, sampling process, and study adherence). Statistical tests as Cohen's kappa agreement; factorial analysis; logistic, Poisson and linear regression; and Kaplan-Meier analysis will be performed, in accordance with the objectives.
Genetically predicted body fat mass and distribution with diabetic kidney disease: A two-sample Mendelian randomization study
Authors: Wang Min , Li Xin , Mei Hang , Huang Zhao-Hui , Liu Yue , Zhu Yong-Hong , Ma Tian-Kui , Fan Qiu-Ling
Published: September 2022

The aim of this study is to apply a Mendelian randomization (MR) design to investigate the potential causal associations between the body mass index (BMI), body fat mass such as trunk fat mass and waist circumference (WC), and diabetic kidney disease (DKD). A two-sample MR study was conducted to obtain exposure and outcome data from previously published studies. The instrumental variables for BMI, trunk fat mass, and WC were selected from genome-wide association study datasets based on summary-level statistics. The random-effects inverse-variance weighted (IVW) method was used for the main analyses, and the weighted median and MR-Egger approaches were complementary. In total, three MR methods suggested that genetically predicted BMI, trunk fat mass, and WC were positively associated with DKD. Using IVW, we found evidence of causal relationships between BMI [odds ratio (OR) = 1.99; 95% confidence interval (CI), 1.47–2.69; p = 7.89 × 10−6], trunk fat mass (OR = 1.80; 95% CI, 1.28–2.53; p = 6.84 × 10−4), WC (OR = 2.48; 95% CI, 1.40–4.42; p = 1.93 × 10−3), and DKD. MR-Egger and weighted median regression also showed directionally similar estimates. Both funnel plots and MR-Egger intercepts showed no directional pleiotropic effects involving the aforementioned variables and DKD. Our MR analysis supported the causal effect of BMI, trunk fat mass, and WC on DKD. Individuals can substantially reduce DKD risk by reducing body fat mass and modifying their body fat distribution.
Study on complications of osteoporosis based on network pharmacology
Authors: Song Zhijing , Zhang Haoling , Jiang Yuhang , Zhao Rui , Pei Xuedong , Ning Haochi , Chen Hailiang , Pan Jing , Gong Yanlong , Song Min , Wang Wei
Published: September 2022

Osteoporosis is a serious threat to human life. Guben Zenggu Granule is an empirical prescription for clinical treatment of osteoporosis. MC3T3-E1 cells are mouse osteogenic precursor cells with osteogenic differentiation, and are classic cells for studying bone metabolism and osteogenic mechanism, as well as mechanical stimulation sensitive cells. Therefore, it can be inferred that Guben Zenggu granule can repair MC3T3-E1 cells under continuous static pressure overload. This study aims to through the network of pharmacology and gene sequencing method, reveal thrift increase bone particles under the condition of continuous static pressure overload on osteogenesis mechanism of MC3T3-E1 cells. In the process of analysis, from a variety of 98 compounds was predicted in the database, a collection of 474 goals, a total of 29,164 difference between two groups of genes. Then, construction of composite targets between cells and predict targets and protein - protein interaction networks, and through the cluster analysis to further explore the relationship between the target. In addition, linkages between target proteins and cells were further identified using Gene Ontology (GO) and Pathways (KEGG Pathway). Finally, the repair effect of Guben Zenggu granule on MC3T3-E1 cells under continuous static pressure overload was verified through experiments, so as to accurately explain the pharmacodynamic mechanism of Traditional Chinese medicine.
The soldiers needed to be awakened: Tumor-infiltrating immune cells
Authors: Yaping Wang , Zhe Wang , Zhuling Chu , Ruolei Li , Pengyu Fan , Lili Guo , Cheng Ji , Bo Zhang , Liuyin Liu , Guangdong Hou , Yaoling Wang , Niuniu Hou , Rui Ling
Published: September 2022

In the tumor microenvironment, tumor-infiltrating immune cells (TIICs) are a key component. Different types of TIICs play distinct roles. CD8+ T cells and natural killer (NK) cells could secrete soluble factors to hinder tumor cell growth, whereas regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) release inhibitory factors to promote tumor growth and progression. In the meantime, a growing body of evidence illustrates that the balance between pro- and anti-tumor responses of TIICs is associated with the prognosis in the tumor microenvironment. Therefore, in order to boost anti-tumor response and improve the clinical outcome of tumor patients, a variety of anti-tumor strategies for targeting TIICs based on their respective functions have been developed and obtained good treatment benefits, including mainly immune checkpoint blockade (ICB), adoptive cell therapies (ACT), chimeric antigen receptor (CAR) T cells, and various monoclonal antibodies. In recent years, the tumor-specific features of immune cells are further investigated by various methods, such as using single-cell RNA sequencing (scRNA-seq), and the results indicate that these cells have diverse phenotypes in different types of tumors and emerge inconsistent therapeutic responses. Hence, we concluded the recent advances in tumor-infiltrating immune cells, including functions, prognostic values, and various immunotherapy strategies for each immune cell in different tumors.
High-quality reference transcriptome construction improves RNA-seq quantification in Oryza sativa indica
Authors: Srikakulam Nagesh , Sridevi Ganapathi , Pandi Gopal
Published: September 2022

The Reference Transcriptomic Dataset (RTD) is an accurate and comprehensive collection of transcripts originating from a given organism. It holds the key to precise transcript quantification and downstream analysis of differential expressions and regulations. Currently, transcriptome annotations for most crop plants are far from complete. For example, Oryza sativa indica (O. sativa indica) is reported to have 40,759 transcripts in the Ensembl database without alternative transcript isoforms and alternative splicing (AS) events. To generate a high-quality RTD, we conducted RNA sequencing of rice leaf samples collected at various time points during Rhizoctonia solani infection. The obtained reads were analyzed by adopting the recently developed computational analysis pipeline to assemble the RTD with increased transcript and AS diversity for O. sativa indica (IndicaRTD). After stringent quality filtering, the newly constructed transcriptome annotation was comprised of 122,968 non-redundant transcripts from 53,695 genes. This study identified many novel transcripts compared to Ensembl deposited data that are important for regulating molecular and physiological processes in the plant system. Currently, the assembled IndicaRTD must allow fast quantification of transcript and gene expression with high precision.
Landscape of circulating metabolic fingerprinting for keloid
Authors: Hu Yu , Zhou Xuyue , Chen Lihao , Li Rong , Jin Shuang , Liu Lingxi , Ju Mei , Luan Chao , Chen Hongying , Wang Ziwei , Huang Dan , Chen Kun , Zhang Jiaan
Published: September 2022

Background

Keloids are a fibroproliferative disease characterized by unsatisfactory therapeutic effects and a high recurrence rate.

Objective

This study aimed to investigate keloid-related circulating metabolic signatures.

Methods

Untargeted metabolomic analysis was performed to compare the metabolic features of 15 keloid patients with those of paired healthy volunteers in the discovery cohort. The circulating metabolic signatures were selected using the least absolute shrinkage. Furthermore, the selection operators were quantified using multiple reaction monitoring-based target metabolite detection methods in the training and test cohorts.

Results

More than ten thousand metabolic features were consistently observed in all the plasma samples from the discovery cohort, and 30 significantly different metabolites were identified. Four differentially expressed metabolites including palmitoylcarnitine, sphingosine, phosphocholine, and phenylalanylisoleucine, were discovered to be related to keloid risk in the training and test cohorts. In addition, using linear and logistic regression models, the respective risk scores for keloids based on a 4-metabolite fingerprint classifier were established to distinguish keloids from healthy volunteers.

Conclusions

In summary, our findings show that the characteristics of circulating metabolic fingerprinting manifest phenotypic variation in keloid onset.
Evaluating the role of IDO1 macrophages in immunotherapy using scRNA-seq and bulk-seq in colorectal cancer
Authors: Liu Xingwu , Yan Guanyu , Xu Boyang , Yu Han , An Yue , Sun Mingjun
Published: September 2022

Background

Macrophage infiltration is crucial for colorectal cancer (CRC) immunotherapy. Detailed classification of macrophage subsets will facilitate the selection of patients suitable for immunotherapy. However, the classification of macrophages in CRC is not currently detailed.

Methods

In this study, we combined single-cell RNA sequencing (scRNA-seq) and bulk-seq to analyze patients with colorectal cancer. scRNA-seq data were used to study cell-cell communication and to differentiate immune-infiltrating cells and macrophage subsets. Bulk-seq data were used to further analyze immune infiltration, clinical features, tumor mutational burden, and expression of immune checkpoint molecules in patients with CRC having different macrophage subsets.

Results

Seven macrophage subpopulations were identified, among which indoleamine 2,3 dioxygenase 1 (IDO1) macrophages had the most significant difference in the degree of infiltration among normal, microsatellite-unstable, and microsatellite-stable populations. We then performed gene set variation analysis using 12 marker genes of IDO1 macrophages and divided the patients into two clusters: high-IDO1 macrophages (H-IDO1M) and low-IDO1 macrophages (L-IDO1M). H-IDO1M showed higher infiltration of immune cells, higher expression of immune checkpoints, and less advanced pathological stages than L-IDO1M (p < 0.05).

Conclusions

This study elucidated that IDO1-macrophage-based molecular subtypes can predict the response to immunotherapy in patients with CRC. The results provide new insights into tumor immunity and help in clinical decisions regarding designing effective immunotherapy for these patients.
Factors affecting RIG-I-Like receptors activation - New research direction for viral hemorrhagic fevers
Authors: Małkowska Paulina , Niedźwiedzka-Rystwej Paulina
Published: September 2022

Viral hemorrhagic fever (VHF) is a term referring to a group of life-threatening infections caused by several virus families (Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae). Depending on the virus, the infection can be mild and can be also characterized by an acute course with fever accompanied by hypervolemia and coagulopathy, resulting in bleeding and shock. It has been suggested that the course of the disease is strongly influenced by the activation of signaling pathways leading to RIG-I-like receptor-dependent interferon production. RIG-I-like receptors (RLRs) are one of two major receptor families that detect viral nucleic acid. RLR receptor activation is influenced by a number of factors that may have a key role in the differences that occur during the antiviral immune response in VHF. In the present study, we collected data on RLR receptors in viral hemorrhagic fevers and described factors that may influence the activation of the antiviral response. RLR receptors seem to be a good target for VHF research, which may contribute to better therapeutic and diagnostic strategies. However, due to the difficulty of conducting such studies in humans, we suggest using Lagovirus europaeus as an animal model for VHF.
Oral manifestations serve as potential signs of ulcerative colitis: A review
Authors: Li Chunyu , Wu Yuqi , Xie Yulang , Zhang You , Jiang Sixin , Wang Jiongke , Luo Xiaobo , Chen Qianming
Published: September 2022

As an immune dysregulation-related disease, although ulcerative colitis (UC) primarily affects the intestinal tract, extraintestinal manifestations of the disease are evident, particularly in the oral cavity. Herein, we have reviewed the various oral presentations, potential pathogenesis, and treatment of oral lesions related to UC. The oral manifestations of UC include specific and nonspecific manifestations, with the former including pyostomatitis vegetans and the latter encompassing recurrent aphthous ulcers, atrophic glossitis, burning mouth syndrome, angular cheilitis, dry mouth, taste change, halitosis, and periodontitis. Although the aetiology of UC has not been fully determined, the factors leading to its development include immune system dysregulation, dysbiosis, and malnutrition. The principle of treating oral lesions in UC is to relieve pain, accelerate the healing of lesions, and prevent secondary infection, and the primary procedure is to control intestinal diseases. Systemic corticosteroids are the preferred treatment options, besides, topical and systemic administration combined with dietary guidance can also be applied. Oral manifestations of UC might accompany or precede the diagnosis of UC, albeit with the absence of intestinal symptoms; therefore, oral lesions, especially pyostomatitis vegetans, recurrent aphthous ulcer and periodontitis, could be used as good mucocutaneous signs to judge the occurrence and severity of UC, thus facilitating the early diagnosis and treatment of UC and avoiding severe consequences, such as colon cancer.
The third dose of mRNA SARS-CoV-2 vaccines enhances the spike-specific antibody and memory B cell response in myelofibrosis patients
Authors: Fiorino Fabio , Ciabattini Annalisa , Sicuranza Anna , Pastore Gabiria , Santoni Adele , Simoncelli Martina , Polvere Jacopo , Galimberti Sara , Baratè Claudia , Sammartano Vincenzo , Montagnani Francesca , Bocchia Monica , Medaglini Donata
Published: September 2022

Vaccination against SARS-CoV-2 using mRNA-based vaccines has been highly recommended for fragile subjects, including myelofibrosis patients (MF). Available data on the immune responsiveness of MF patients to mRNA SARS-CoV-2 vaccination, and the impact of the therapy with the JAK inhibitor ruxolitinib, are still fragmented. Here, we profile the spike-specific IgG and memory B-cell response in MF patients, treated or not with ruxolitinib, after the second and the third dose of SARS-CoV-2 BNT162b2 (BioNTech) and mRNA-1273 (Moderna) vaccines. Plasma and peripheral blood mononuclear cells samples were collected before vaccination, post the second and the third doses and tested for spike-specific antibodies, ACE2/RBD antibody inhibition binding activity and spike-specific B cells. The third vaccine dose significantly increased the spike-specific IgG titers in both ruxolitinib-treated and untreated patients, and strongly enhanced the percentage of subjects with antibodies capable of in vitro blocking ACE2/RBD interaction, from 50% up to 80%. While a very low frequency of spike-specific B cells was measured in blood 7 days after the second vaccination dose, a strong and significant increase was elicited by the third dose administration, generating a B cell response similar to the one detected in healthy controls. Despite the overall positive impact of the third dose in MF patients, two patients that were under active concomitant immunosuppressive treatment at the time of vaccination, and a patient that received lymphodepleting therapies in the past, remained low responders. The third mRNA vaccine dose strongly increases the SARS-CoV-2 specific humoral and B cell responses in MF patients, promoting a reactivation of the immune response similar to the one observed in healthy controls.
Foot-and-mouth disease virus non-structural protein 2B downregulates the RLR signaling pathway via degradation of RIG-I and MDA5
Authors: Weerawardhana Asela , Uddin Md Bashir , Choi Joo-Hyung , Pathinayake Prabuddha , Shin Sung Ho , Chathuranga Kiramage , Park Jong-Hyeon , Lee Jong-Soo
Published: September 2022

Foot-and-mouth disease virus (FMDV) is a single-stranded, positive-sense RNA virus containing at least 13 proteins. Many of these proteins show immune modulation capabilities. As a non-structural protein of the FMDV, 2B is involved in the rearrangement of the host cell membranes and the disruption of the host secretory pathway as a viroporin. Previous studies have also shown that FMDV 2B plays a role in the modulation of host type-I interferon (IFN) responses through the inhibition of expression of RIG-I and MDA5, key cytosolic sensors of the type-I IFN signaling. However, the exact molecular mechanism is poorly understood. Here, we demonstrated that FMDV 2B modulates host IFN signal pathway by the degradation of RIG-I and MDA5. FMDV 2B targeted the RIG-I for ubiquitination and proteasomal degradation by recruiting E3 ubiquitin ligase ring finger protein 125 (RNF125) and also targeted MDA5 for apoptosis-induced caspase-3- and caspase-8-dependent degradation. Ultimately, FMDV 2B significantly inhibited RNA virus-induced IFN-β production. Importantly, we identified that the C-terminal amino acids 126-154 of FMDV 2B are essential for 2B-mediated degradation of the RIG-I and MDA5. Collectively, these results provide a clearer understanding of the specific molecular mechanisms used by FMDV 2B to inhibit the IFN responses and a rational approach to virus attenuation for future vaccine development.
The function of omega-3 polyunsaturated fatty acids in response to cadmium exposure
Authors: Chen Zhi , Lu Qinyue , Wang Jiacheng , Cao Xiang , Wang Kun , Wang Yuhao , Wu Yanni , Yang Zhangping
Published: September 2022

Throughout history, pollution has become a part of our daily life with the improvement of life quality and the advancement of industry and heavy industry. In recent years, the adverse effects of heavy metals, such as cadmium (Cd), on human health have been widely discussed, particularly on the immune system. Here, this review summarizes the available evidence on how Cd exposure may affect health. By analyzing the general manifestations of inflammation caused by Cd exposure, we find that the role of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in vivo can counteract Cd-induced harm. Additionally, we elucidate the effects of n-3 PUFAs on the immune system, and analyze their prophylactic and therapeutic effects on Cd exposure. Overall, this review highlights the role of n-3 PUFAs in the pathological changes induced by Cd exposure. Although n-3 PUFAs remain to be verified whether they can be used as therapeutic agents, as rehabilitation therapy, supplementation with n-3 PUFAs is reliable and effective.
Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease
Authors: Ouahed Jodie Deborah
Published: September 2022

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract, including Crohn’s disease, ulcerative colitis and inflammatory bowel disease-undefined (IBD-U). IBD are understood to be multifactorial, involving genetic, immune, microbial and environmental factors. Advances in next generation sequencing facilitated the growing identification of over 80 monogenic causes of IBD, many of which overlap with Inborn errors of immunity (IEI); Approximately a third of currently identified IEI result in gastrointestinal manifestations, many of which are inflammatory in nature, such as IBD. Indeed, the gastrointestinal tract represents an opportune system to study IEI as it consists of the largest mass of lymphoid tissue in the body and employs a thin layer of intestinal epithelial cells as the critical barrier between the intestinal lumen and the host. In this mini-review, a selection of pertinent IEI resulting in monogenic IBD is described involving disorders in the intestinal epithelial barrier, phagocytosis, T and B cell defects, as well as those impairing central and peripheral tolerance. The contribution of disrupted gut-microbiota-host interactions in disturbing intestinal homeostasis among patients with intestinal disease is also discussed. The molecular mechanisms driving pathogenesis are reviewed along with the personalized therapeutic interventions and investigational avenues this growing knowledge has enabled.
Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis
Authors: Ruiz Maria Julia , Siracusano Gabriel , Cottignies-Calamarte Andréa , Tudor Daniela , Real Fernando , Zhu Aiwei , Pastori Claudia , Capron Claude , Rosenberg Arielle R. , Temperton Nigel , Cantoni Diego , Liao Hanqing , Ternette Nicola , Moine Pierre , Godement Mathieu , Geri Guillaume , Chiche Jean-Daniel , Annane Djillali , Cramer Bordé Elisabeth , Lopalco Lucia , Bomsel Morgane
Published: September 2022

The role of the mucosal pulmonary antibody response in coronavirus disease 2019 (COVID-19) outcome remains unclear. Here, we found that in bronchoalveolar lavage (BAL) samples from 48 patients with severe COVID-19-infected with the ancestral Wuhan virus, mucosal IgG and IgA specific for S1, receptor-binding domain (RBD), S2, and nucleocapsid protein (NP) emerged in BAL containing viruses early in infection and persist after virus elimination, with more IgA than IgG for all antigens tested. Furthermore, spike-IgA and spike-IgG immune complexes were detected in BAL, especially when the lung virus has been cleared. BAL IgG and IgA recognized the four main RBD variants. BAL neutralizing titers were higher early in COVID-19 when virus replicates in the lung than later in infection after viral clearance. Patients with fatal COVID-19, in contrast to survivors, developed higher levels of mucosal spike-specific IgA than IgG but lost neutralizing activities over time and had reduced IL-1β in the lung. Altogether, mucosal spike and NP-specific IgG and S1-specific IgA persisting after lung severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance and low pulmonary IL-1β correlate with COVID-19 fatal outcome. Thus, mucosal SARS-CoV-2-specific antibodies may have adverse functions in addition to protective neutralization.

Highlights

Mucosal pulmonary antibody response in COVID-19 outcome remains unclear. We show that in severe COVID-19 patients, mucosal pulmonary non-neutralizing SARS-CoV-2 IgA persit after viral clearance in the lung. Furthermore, low lung IL-1β correlate with fatal COVID-19. Altogether, mucosal IgA may exert harmful functions beside protective neutralization.