Comparison of stromal vascular fraction cell composition between Coleman fat and extracellular matrix/stromal vascular fraction gel.

As a mechanically condensed product of Coleman fat, extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) eliminates adipocytes, concentrates SVF cells, and improves fat graft retention. This study aims to compare SVF cell composition between Coleman fat and ECM/SVF-gel. Matched Coleman fat and ECM/SVF-gel of 28 healthy women were subjected to RNA-seq, followed by functional enrichment and cell-type-specific enrichment analyses, and deconvolution of SVF cell subsets, reconstructing SVF cell composition in the transcriptome level. ECM/SVF-gels had 9 upregulated and 73 downregulated differentially expressed genes (DEGs). Downregulated DEGs were mainly associated with inflammatory and immune responses, and enriched in fat macrophages. M2 macrophages, resting CD4+ memory T cells, M1 macrophages, resting mast cells, and M0 macrophages ranked in the top five most prevalent immune cells in the two groups. The proportions of the principal non-immune cells (e.g., adipose-derived stem cells, pericytes, preadipocytes, microvascular endothelial cells) had no statistical differences between the two groups. Our findings reveal ECM/SVF-gels share the same dominant immune cells beneficial to fat graft survival with Coleman fat, but exhibiting obvious losses of immune cells (especially macrophages), while non-immune cells necessary for adipose regeneration might have no significant loss in ECM/SVF-gels and their biological effects could be markedly enhanced by the ECM/SVF-gel's condensed nature.

Exploring the Association between Cathepsin B and Parkinson's Disease.

OBJECTIVE: The aim of this study is to investigate the association between Cathepsin B and Parkinson's Disease (PD), with a particular focus on determining the role of N-acetylaspartate as a potential mediator. METHODS: We used summary-level data from Genome-Wide Association Studies (GWAS) for a two-sample Mendelian randomization (MR) analysis, exploring the association between Cathepsin B (3301 cases) and PD (4681 cases). A sequential two-step MR approach was applied (8148 cases) to study the role of N-acetylaspartate. RESULTS: The MR analysis yielded that genetically predicted elevated Cathepsin B levels correlated with a reduced risk of developing PD (p = 0.0133, OR: 0.9171, 95% CI: 0.8563-0.9821). On the other hand, the analysis provided insufficient evidence to determine that PD affected Cathepsin B levels (p = 0.8567, OR: 1.0035, 95% CI: 0.9666-1.0418). The estimated effect of N-acetylaspartate in this process was 7.52% (95% CI = -3.65% to 18.69%). CONCLUSIONS: This study suggested that elevated Cathepsin B levels decreased the risk of developing PD, with the mediation effect of N-acetylaspartate. Further research is needed to better understand this relationship.

Exogenous salicylic acid induces defense responses in tea plants against Toxoptera aurantii (Hemiptera: Aphididae).

Toxoptera aurantii is one of the most destructive pests, threatening the yield and quality of tea plantations. The salicylic acid (SA)-mediated signaling pathway is vital for the induction of plant defense responses; however, its role in tea plant resistance to T. aurantii remains unclear. Thus, this study used and electrical penetration graph and monitoring of population dynamics to evaluate the effects of exogenous SA application on T. aurantii feeding behavior and population growth in tea seedlings. Moreover, the effects of SA treatment on the activities of defense-related enzymes were analyzed. Probe counts and the duration of xylem sap ingestion were significantly higher in SA-treated plants than those in the control group. The total duration of passive phloem ingestion was significantly decreased in 0.5 mmol/l SA-treated plants, and the application of 0.5, 1, and 4 mmol/l SA significantly inhibited T. aurantii population growth. In addition, the activities of polyphenol oxidase, peroxidase, and superoxide dismutase were significantly increased in the 0.5 mmol/l SA-treated plants. Overall, this study demonstrates the capacity of exogenous SA to activate defense responses against T. aurantii. These results have crucial implications for understanding the mechanisms of enhanced resistance, thereby providing a sustainable approach for managing T. aurantii.

Unraveling the prognostic significance and molecular characteristics of tumor-infiltrating B lymphocytes in clear cell renal cell carcinoma through a comprehensive bioinformatics analysis.

Introduction: Clear cell renal cell carcinoma (ccRCC) is a prevalent subtype of kidney cancer that exhibits a complex tumor microenvironment, which significantly influences tumor progression and immunotherapy response. In recent years, emerging evidence has underscored the involvement of tumor-infiltrating B lymphocytes (TIL-Bs), a crucial component of adaptive immunity, and their roles in ccRCC as compared to other tumors. Therefore, the present study endeavors to systematically explore the prognostic and molecular features of TIL-Bs in ccRCC. Methods: Initially, xCell algorithm was used to predict TIL-Bs in TCGA-KIRC and other ccRCC transcriptomic datasets. The Log-Rank test and Cox regression were applied to explore the relationship of B-cells with ccRCC survival. Then, we used WGCNA method to identify important modules related to TIL-Bs combining Consensus subcluster and scRNA-seq data analysis. To narrow down the prospective biomarkers, a prognostic signature was proposed. Next, we explored the feature of the signature individual genes and the risk-score. Finally, the potential associations of signature with clinical phenotypes and drugs were investigated. Results: Preliminary, we found ccRCC survival was negatively associated with TIL-Bs, which was confirmed by other datasets. Afterwards, ten co-expression modules were identified and a distinct ccRCC cluster was subsequently detected. Moreover, we assessed the transcriptomic alteration of B-cell in ccRCC and a relevant B-cell subtype was also pinpointed. Based on two core modules (brown, red), a 10-gene signature (TNFSF13B, SHARPIN, B3GAT3, IL2RG, TBC1D10C, STAC3, MICB, LAG3, SMIM29, CTLA4) was developed in train set and validated in test sets. These biomarkers were further investigated with regards to their differential expression and correlation with immune characteristics, along with risk-score related mutations and pathways. Lastly, we established a nomogram combined tumor grade and discovered underlying drugs according to their sensitivity response. Discussion: In our research, we elucidated the remarkable association between ccRCC and B-cells. Then, we detected several key gene modules, together with close patient subcluster and B-cell subtype,which could be responsible for the TIL-Bs in ccRCC. Moreover, we proposed a 10-gene signature and investigated its molecular features from multiple perspectives. Overall, understanding the roles of TIL-Bs could aid in the immunotherapeutic approaches for ccRCC, which deserve further research to clarify the implications for patient prognosis and treatment.

Different Tea Germplasms Distinctly Influence the Adaptability of Toxoptera aurantii (Hemiptera: Aphididae).

Aphids are typical phloem-sucking insect pests. A good understanding regarding their feeding behavior and population dynamics are critical for evaluating host adaptation and screening of aphid-resistant resources. Herein, the adaptability of Toxoptera aurantii (Boyer) (Hemiptera: Aphididae) to different hosts was evaluated via electropenetrography and an age-stage, two-sex life table on six tea germplasms: Zikui (ZK), Zhongcha108 (ZC108), Zhongcha111 (ZC111), Qianmei419 (QM419), Meitan5 (MT5), and Fudingdabaicha (FD). Our findings revealed that the feeding activities of T. aurantii differed considerably among the host plants. T. aurantii exhibited significantly more pathway activities on ZK and FD than on the other hosts. However, the duration of feeding of T. aurantii on ZK phloem considerably decreased compared with those of the other germplasms. Life parameters indicated that T. aurantii exhibited the highest intrinsic rate of increase (r), net reproductive rate (R0), and finite rate of increase (λ) on MT5, and the maximum values of total longevity and oviposition period were recorded on FD; these variables were reduced significantly on ZK. The results of our study demonstrate that T. aurantii can successfully survive on the six tea germplasms; however, ZK was less suitable for T. aurantii and should be considered as a potential source of resistance in breeding and Integrated Pest Management.

Uncovering neuroinflammation-related modules and potential repurposing drugs for Alzheimer's disease through multi-omics data integrative analysis.

Background: Neuroinflammation is one of the key factors leading to neuron death and synapse dysfunction in Alzheimer's disease (AD). Amyloid-ß (Aß) is thought to have an association with microglia activation and trigger neuroinflammation in AD. However, inflammation response in brain disorders is heterogenous, and thus, it is necessary to unveil the specific gene module of neuroinflammation caused by Aß in AD, which might provide novel biomarkers for AD diagnosis and help understand the mechanism of the disease. Methods: Transcriptomic datasets of brain region tissues from AD patients and the corresponding normal tissues were first used to identify gene modules through the weighted gene co-expression network analysis (WGCNA) method. Then, key modules highly associated with Aß accumulation and neuroinflammatory response were pinpointed by combining module expression score and functional information. Meanwhile, the relationship of the Aß-associated module to the neuron and microglia was explored based on snRNA-seq data. Afterward, transcription factor (TF) enrichment and the SCENIC analysis were performed on the Aß-associated module to discover the related upstream regulators, and then a PPI network proximity method was employed to repurpose the potential approved drugs for AD. Results: A total of 16 co-expression modules were primarily obtained by the WGCNA method. Among them, the green module was significantly correlated with Aß accumulation, and its function was mainly involved in neuroinflammation response and neuron death. Thus, the module was termed the amyloid-ß induced neuroinflammation module (AIM). Moreover, the module was negatively correlated with neuron percentage and showed a close association with inflammatory microglia. Finally, based on the module, several important TFs were recognized as potential diagnostic biomarkers for AD, and then 20 possible drugs including ibrutinib and ponatinib were picked out for the disease. Conclusion: In this study, a specific gene module, termed AIM, was identified as a key sub-network of Aß accumulation and neuroinflammation in AD. Moreover, the module was verified as having an association with neuron degeneration and inflammatory microglia transformation. Moreover, some promising TFs and potential repurposing drugs were presented for AD based on the module. The findings of the study shed new light on the mechanistic investigation of AD and might make benefits the treatment of the disease.

Repetitive transcranial magnetic stimulation may be superior to drug therapy in the treatment of Alzheimer's disease: A systematic review and Bayesian network meta-analysis.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation therapy that is primarily used to treat a variety of neuropsychiatric conditions. Recently, previous research reports stated that rTMS have the characteristics of neurorestorative in Alzheimer's disease (AD). However, the relevant clinical research evidence has not been fully summarized. METHODS: This article performed a network meta-analysis of individual participant data from eligible studies searched in PubMed, Embase, and the Cochrane Library from inception to March 31, 2022. The drug treatments involved were acetylcholinesterase inhibitors (AChEIs), N-methyl-d-aspartate (NMDA), anti-amyloid-beta (Aß), and some new targeted therapeutic drugs. RESULTS: A total of 15, 548 individuals with AD disease in 57 randomized clinical trials (RCTs) were included in this meta-analysis. The results indicated that the patients who received rTMS treatment (standard mean difference [SMD]: 0.65; 95% confidence interval [CI]: 0.22-1.07) had a better MMSE score than placebo. Treatment outcome analysis showed that, compared with multiple pharmacological interventions, rTMS acquired the greatest probability rank with the best cognitive improvement in MMSE score [the surface under the cumulative ranking curve (SUCRA) 93.3%] and ADAS-cog score (SUCRA 86.7%). At the same time, rTMS treatment had the lowest rank in the adverse events (SUCRA 24.1%) except for the placebo group (SUCRA 19.1%). CONCLUSION: Compared with the current clinical drug treatment, rTMS demonstrated better cognitive function improvement and fewer adverse events in AD patients. Therefore, rTMS shows broad prospects in the treatment of Alzheimer's disease, and it is worth being widely popularized in clinic.

Rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren's syndrome shared megakaryocyte expansion in peripheral blood.

OBJECTIVES: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) share many clinical manifestations and serological features. The aim of this study was to identify the common transcriptional profiling and composition of immune cells in peripheral blood in these autoimmune diseases (ADs). METHODS: We analysed bulk RNA-seq data for enrichment of biological processes, transcription factors (TFs) and deconvolution-based immune cell types from peripheral blood mononuclear cells (PBMCs) in 119 treatment-naive patients (41 RA, 38 pSS, 28 SLE and 12 polyautoimmunity) and 20 healthy controls. The single-cell RNA-seq (scRNA-seq) and flow cytometry had been performed to further define the immune cell subsets on PBMCs. RESULTS: Similar transcriptional profiles and common gene expression signatures associated with nucleosome assembly and haemostasis were identified across RA, SLE, pSS and polyautoimmunity. Distinct TF ensembles and gene regulatory network were mainly enriched in haematopoiesis. The upregulated cell-lineage-specific TFs PBX1, GATA1, TAL1 and GFI1B demonstrated a strong gene expression signature of megakaryocyte (MK) expansion. Gene expression-based cell type enrichment revealed elevated MK composition, specifically, CD41b+CD42b+ and CD41b+CD61+ MKs were expanded, further confirmed by flow cytometry in these ADs. In scRNA-seq data, MKs were defined by TFs PBX1/GATA1/TAL1 and pre-T-cell antigen receptor gene, PTCRA. Cellular heterogeneity and a distinct immune subpopulation with functional enrichment of antigen presentation were observed in MKs. CONCLUSIONS: The identification of MK expansion provided new insights into the peripheral immune cell atlas across RA, SLE, pSS and polyautoimmunity. Aberrant regulation of the MK expansion might contribute to the pathogenesis of these ADs.

Increase of ALCAM and VCAM-1 in the plasma predicts the Alzheimer's disease.

Cell adhesion molecules (CAM) are crucial in several pathological inflammation processes in Alzheimer's disease (AD). However, their potential for clinical diagnostics remains unknown. The present investigation evaluated the clinical significance of ALCAM, VCAM-1, NCAM, and ICAM-1 levels in the plasma of participants with cognitive impairment (44 patients with mild cognitive impairment, 71 patients with Alzheimer's dementia, and 18 patients with other dementia) and 28 controls with normal cognitive ability. We also detected plasma levels of multiple inflammatory factors (IFN-gamma, IL-18, IL-1beta, IL-13, IL-8, IL-7, CCL11, MCP-1, TSLP, IL-10, BDNF, IL-17, IL-5, TREM-1) using Multiplex liquid chip and plasma levels of Abeta1-42 and Abeta1-40 using liquid-phase flow cytometry (FCM). Our findings demonstrated a correlation of ALCAM and VCAM-1 with age, the severity of cognitive decline, and MTA, but no significant difference between groups for NCAM and ICAM-1. ALCAM and VCAM-1 both demonstrated a positive correlation with the degree of atrophy in the medial temporal lobe structure. Further analysis revealed no significant correlation in plasma between VCAM-1, ALCAM and Abeta1-40, Abeta1-42. Nevertheless, there was a significant correlation between VCAM-1, ALCAM and many inflammatory factors. Furthermore, the predictive value of ALCAM and VCAM-1 for AD was assessed using a multi-parameter regression model. ALCAM and VCAM-1 in combination with ApoE4, education, age, and MMSE could predict AD with high precision (AUC=0.891; AIC=146.9) without imaging diagnosis. ALCAM and VCAM-1 combination improved the predictive accuracy significantly. In a nutshell, these findings revealed ALCAM and VCAM-1 as reliable indicators of Alzheimer's disease.