Spatiotemporal formation of glands in plants is modulated by MYB-like transcription factors.

About one third of vascular plants develop glandular trichomes, which produce defensive compounds that repel herbivores and act as a natural biofactory for important pharmaceuticals such as artemisinin and cannabinoids. However, only a few regulators of glandular structures have been characterized so far. Here we have identified two closely-related MYB-like genes that redundantly inhibit the formation of glandular cells in tomatoes, and they are named as GLAND CELL REPRESSOR (GCR) 1 and 2. The GCR genes highly express in the apical cells of tomato trichomes, with expression gradually diminishing as the cells transition into glands. The spatiotemporal expression of GCR genes is coordinated by a two-step inhibition process mediated by SlTOE1B and GCRs. Furthermore, we demonstrate that the GCR genes act by suppressing Leafless (LFS), a gene that promotes gland formation. Intriguingly, homologous GCR genes from tobacco and petunia also inhibit gland formation, suggesting that the GCR-mediated repression mechanism likely represents a conserved regulatory pathway for glands across different plant species.

Unleashing the power of complement activation: unraveling renal damage in human anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (GBM) disease is a rare but life-threatening autoimmune disorder characterized by rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Renal biopsies of anti-GBM patients predominantly show linear deposition of IgG and complement component 3 (C3), indicating a close association between antigen-antibody reactions and subsequent complement activation in the pathogenesis of the disease. All three major pathways of complement activation, including the classical, lectin, and alternative pathways, are involved in human anti-GBM disease. Several complement factors, such as C3, C5b-9, and factor B, show a positive correlation with the severity of the renal injury and act as risk factors for renal outcomes. Furthermore, compared to patients with single positivity for anti-GBM antibodies, individuals who are double-seropositive for anti-neutrophil cytoplasmic antibody (ANCA) and anti-GBM antibodies exhibit a unique clinical phenotype that lies between ANCA-associated vasculitis (AAV) and anti-GBM disease. Complement activation may serve as a potential "bridge" for triggering both AAV and anti-GBM conditions. The aim of this article is to provide a comprehensive review of the latest clinical evidence regarding the role of complement activation in anti-GBM disease. Furthermore, potential therapeutic strategies targeting complement components and associated precautions are discussed, to establish a theoretical basis for complement-targeted therapies.

Exploring the role of LIAS-related cuproptosis in systemic lupus erythematosus.

BACKGROUND: Cuproptosis is a novel mode of cell death, which is strongly related to energy metabolism in mitochondria and regulated by protein lipoylation. Currently, the molecular mechanisms of cuproptosis-related genes (CRGs) involved in systemic lupus erythematosus (SLE) largely remained unclear, our study is aimed to explore the mechanisms of cuproptosis and CRGs involved in SLE. METHODS: Bulk RNA-seq datasets were collected to display the expressions of CRGs in peripheral blood mononuclear cells (PBMCs) of SLE and healthy individuals, and then ROC analysis was used to establish the diagnostic models of CRGs. Next, the immune infiltration analyses were applied to reveal the difference of immune cells infiltration in LIAS-low and LIAS-high group. Additionally, WGCNA analysis was performed to find the gene modules significantly correlated with the LIAS expression level. We also performed the functional enrichment analyses for LIAS-related gene modules to determine the potential pathways involved in the development of SLE. Finally, scRNA-seq dataset was used to cluster immune cell subsets, reveal the activated pathways, and study cell-cell interactions in LIAS-low and LIAS-high cells. RESULT: We found CDKN2A was significantly increased and LIAS was significantly decreased in SLE patients compared with healthy individuals. The AUC score showed that LIAS had a great diagnostic value than other CRGs. Additionally, the results of immune infiltration analyses showed that immune cells proportion were diverse in LIAS-low and LIAS-high samples. The gene sets related to LIAS expression level were involved in dephosphorylation of JAK1 by SHP1, phosphorylation of STAT2, cytokine signaling in immune system, expression of interferon-alpha and beta, inhibition of JAK kinase activity by SOCS1/3, and so on. Finally, the results of cell-cell communication showed that CCL- (CCL5 + CCR1) and ANNEXIN- (ANXA1 + FPR1) might play an essential role in the communication network between LIAS-low and LIAS-high cells. CONCLUSION: Above findings inferred that LIAS-mediated cuproptosis might involve in a comprehensive cellular and molecular mechanism to cause the occurrence and development of SLE.

Integrated multi-omics and bioinformatic methods to reveal the mechanisms of sinomenine against diabetic nephropathy.

OBJECTIVES: Diabetic Nephropathy (DN) is a serious complication of diabetes, the diagnosis and treatment of DN is still limited. Sinomenine (SIN) is an active extract of herbal medicine and has been applied into the therapy of DN. METHODS: In the part of bioinformatic analyses, network pharmacology and molecular docking analyses were conducted to predict the important pathway of SIN treatment for DN. In-vivo study, DN rats were randomized to be treated with vehicle or SIN (20 mg/kg or 40 mg/kg) daily by gavage for 8 weeks. Then, the pharmacological effect of SIN on DN and the potential mechanisms were also evaluated by 24 h albuminuria, histopathological examination, transcriptomics, and metabolomics. RESULTS: Firstly, network pharmacology and molecular docking were performed to show that SIN might improve DN via AGEs/RAGE, IL-17, JAK, TNF pathways. Urine biochemical parameters showed that SIN treatment could significantly reduce 24 h albuminuria of DN rats. Transcriptomics analysis found SIN could affect DN progression via inflammation and EMT pathways. Metabolic pathway analysis found SIN would mainly involve in arginine biosynthesis, linoleic acid metabolism, arachidonic acid metabolism, and glycerophospholipid metabolism to affect DN development. CONCLUSIONS: We confirmed that SIN could inhibit the progression of DN via affecting multiple genes and metabolites related pathways.

The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study.

Background: Previous epidemiological and other studies have shown an association between major depressive disorder (MDD) and migraine. However, the causal relationship between them remains unclear. Therefore, this study aimed to investigate the causal relationship between MDD and migraine using a bidirectional, two-sample Mendelian randomization (MR) approach. Methods: Data on MDD and migraine, including subtypes with aura migraine (MA) and without aura migraine (MO), were gathered from a publicly available genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) utilized as instrumental variables (IVs) were then screened by adjusting the intensity of the connection and removing linkage disequilibrium. To explore causal effects, inverse variance weighting (IVW) was used as the primary analysis method, with weighted median, MR-Egger, simple mode, and weighted mode used as supplementary analytic methods. Furthermore, heterogeneity and pleiotropy tests were carried out. Cochran's Q-test with IVW and MR-Egger was used to assess heterogeneity. Pleiotropy testing was carried out using the MR-Egger intercept and MR-PRESSO analysis methods. A leave-one-out analysis was also used to evaluate the stability of the findings. Finally, we used migraine (MA and MO) levels to deduce reverse causality with MDD risk. Results: Random effects IVW results were (MDD-Migraine: odds ratio (OR), 1.606, 95% confidence interval (CI), 1.324-1.949, p = 1.52E-06; MDD-MA: OR, 1.400, 95%CI, 1.067-1.8378, p = 0.015; MDD-MO: OR, 1.814, 95%CI, 1.277-2.578, p = 0.0008), indicating a causal relationship between MDD levels and increased risk of migraine (including MA and MO). In the inverse MR analysis, the findings were all negative, while in sensitivity analyses, the results were robust except for the study of MA with MDD. Conclusion: Our study confirms a causal relationship between MDD levels and increased risk of migraine, MA, and MO. There was little evidence in the reverse MR analysis to suggest a causal genetic relationship between migraine (MA and MO) and MDD risk levels.

Klotho's impact on diabetic nephropathy and its emerging connection to diabetic retinopathy.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide and is a significant burden on healthcare systems. α-klotho (klotho) is a protein known for its anti-aging properties and has been shown to delay the onset of age-related diseases. Soluble klotho is produced by cleavage of the full-length transmembrane protein by a disintegrin and metalloproteases, and it exerts various physiological effects by circulating throughout the body. In type 2 diabetes and its complications DN, a significant decrease in klotho expression has been observed. This reduction in klotho levels may indicate the progression of DN and suggest that klotho may be involved in multiple pathological mechanisms that contribute to the onset and development of DN. This article examines the potential of soluble klotho as a therapeutic agent for DN, with a focus on its ability to impact multiple pathways. These pathways include anti-inflammatory and oxidative stress, anti-fibrotic, endothelial protection, prevention of vascular calcification, regulation of metabolism, maintenance of calcium and phosphate homeostasis, and regulation of cell fate through modulation of autophagy, apoptosis, and pyroptosis pathways. Diabetic retinopathy shares similar pathological mechanisms with DN, and targeting klotho may offer new insights into the prevention and treatment of both conditions. Finally, this review assesses the potential of various drugs used in clinical practice to modulate klotho levels through different mechanisms and their potential to improve DN by impacting klotho levels.

Efficacy of Cold Atmospheric Plasma Therapy on Chronic Wounds: An Updated Systematic Review and Meta-Analysis of RCTs.

Objective: A previous meta-analysis has revealed that cold atmospheric plasma (CAP) might not be clinically beneficial to chronic wounds. However, several new randomized controlled trials (RCTs) reported that CAP was an effective treatment option for accelerating wound healing in chronic wounds. The purpose of this review is to incorporate these new results and evaluate the efficacy of CAP in chronic wounds. Methods: The major databases, including PubMed, Embase, Cochrane Library, and Web of Science, were searched for articles related to CAP treatment in chronic wounds until March 21, 2022. The literature retrieval and evaluation were carried out by two independent researchers. Result: A total of 13 randomized clinical trials published between 2010 and 2022 were finally included. CAP therapy showed to be more effective in reducing the area of wounds (mean difference (MD): -1.74, 95%; confidence interval (CI): [-3.14, -0.33], p = 0.02), compared with non-CAP treatments. The immediate reduction of the bacterial load was higher in the CAP group than in the control group. (MD: -0.37, 95%; CI: [-0.7, -0.05], p = 0.02). Conclusion: No significant changes were found in long-term antibacterial efficacy and pain perception between the two groups. However, more RCTs of excellent methodological quality are required to confirm technical details of the source of AP and the appropriate duration of the treatment with plasma.

[Neurofeedback technology based on functional near infrared spectroscopy imaging and its applications].

Neurofeedback (NF) technology based on electroencephalogram (EEG) data or functional magnetic resonance imaging (fMRI) has been widely studied and applied. In contrast, functional near infrared spectroscopy (fNIRS) has become a new technique in NF research in recent years. fNIRS is a neuroimaging technology based on hemodynamics, which has the advantages of low cost, good portability and high spatial resolution, and is more suitable for use in natural environments. At present, there is a lack of comprehensive review on fNIRS-NF technology (fNIRS-NF) in China. In order to provide a reference for the research of fNIRS-NF technology, this paper first describes the principle, key technologies and applications of fNIRS-NF, and focuses on the application of fNIRS-NF. Finally, the future development trend of fNIRS-NF is prospected and summarized. In conclusion, this paper summarizes fNIRS-NF technology and its application, and concludes that fNIRS-NF technology has potential practicability in neurological diseases and related fields. fNIRS can be used as a good method for NF training. This paper is expected to provide reference information for the development of fNIRS-NF technology.

Manual Therapy and Related Interventions for Carpal Tunnel Syndrome: A Systematic Review and Meta-Analysis.

Objective: Systematic review and meta-analysis to assess the efficacy of Manual therapy and related interventions in the treatment of carpal tunnel syndrome (CTS) based on Boston carpal tunnel questionnaire. Design: Systematic review and meta-analysis. Subjects: Carpal tunnel syndrome. Interventions: Manual therapy and related interventions versus other therapies or manual therapy and related interventions plus other therapies versus other therapies. Outcomes measures: Boston carpal tunnel questionnaire. Results: A total of 6 studies were included, including 211 cases in the manual therapy group and 211 cases in the control group. The quality of the included articles was high, and the results of meta-analysis showed that manual therapy and related interventions were superior in terms of improving the Boston carpal tunnel questionnaire Symptom Severity score in patients with CTS (standardised mean difference [SMD] -1.13, 95% CI -1.40 to -0.87), were superior to control groups in terms of improving the Boston carpal tunnel questionnaire functional capacity scale in patients with CTS (SMD -1.01,95% CI -1.24 to -0.77). Conclusion: The results of this meta-analysis suggested that manual therapy and related interventions were better than control groups in treating CTS. Manual therapy and related interventions could relieve the symptoms of patients with CTS and promote the recovery of hand function. Manual therapy and related interventions should be considered clinically effective methods for treating CTS. Registration: The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; No. CRD 42020201389). Contribution of the Article: Manual therapy and related interventions could relieve the symptoms of patients with CTS and promote the recovery of hand function. Manual therapy and related interventions should be considered clinically effective methods for treating CTS.

Efficacy of Acupuncture Treatment for Postprandial Distress Syndrome: A Systematic Review and Meta-Analysis.

Objective: This systematic review and meta-analysis was conducted to assess the efficacy of acupuncture treatment for postprandial distress syndrome (PDS). Methods: Search the Web of Science, the Cochrane Library, PubMed, and Embase databases with acupuncture randomized controlled trials for the treatment of patients with PDS. Strictly according to inclusion and exclusion quality assessment standards, the qualified ones are used to study the optimum extraction and data by two independent reviewers. Stata 15.0 software was used for meta-analysis. Result: We initially identified 63 studies, of which five (1253 participants) were eventually included in our analysis. There were 643 cases in the experimental group and 610 cases in the control group. Acupuncture had a significant effect on the total therapeutic effect (OTE) at week 4 (OR 4.74, 95% CI 02.88-7.83, Z = 6.10, P = 0 < 0.05). Significantly improved NDI (Nepean dyspepsia index) scores of PDS patients at week 4 (SMD 0.61, 95% CI 0.48 to 0.74). Significantly improved NDI scores in PDS patients at week 16 (SMD 0.49, 95% CI 0.27 to 0.71). After acupuncture treatment, the SID (dyspepsia symptom index) score of PDS patients decreased significantly at week 4 (SMD-0.52, 95% CI -0.73 to -0.32) and week 16 (SMD-0.59, 95% CI -0.81 to -0.36). Postprandial satiety scores (SMD-0.63, 95% CI -0.76 to -0.50) and early satiety scores (SMD-0.51, 95% CI -0.64 to -0.37) were also significantly lower at week 4 after acupuncture. Conclusion: This study highlighted that the acupuncture could significantly improve the overall therapeutic effect of PDS patients, alleviate the symptoms of postprandial fullness and early satiety, and improve the quality of life of patients. Our results supported that acupuncture was an effective therapeutic strategy for postprandial distress syndrome.

Investigation of the Mechanism of Complement System in Diabetic Nephropathy via Bioinformatics Analysis.

OBJECTIVES: Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) throughout the world, and the identification of novel biomarkers via bioinformatics analysis could provide research foundation for future experimental verification and large-group cohort in DN models and patients. METHODS: GSE30528, GSE47183, and GSE104948 were downloaded from Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs). The difference of gene expression between normal renal tissues and DN renal tissues was firstly screened by GEO2R. Then, the protein-protein interactions (PPIs) of DEGs were performed by STRING database, the result was integrated and visualized via applying Cytoscape software, and the hub genes in this PPI network were selected by MCODE and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to determine the molecular mechanisms of DEGs involved in the progression of DN. Finally, the Nephroseq v5 online platform was used to explore the correlation between hub genes and clinical features of DN. RESULTS: There were 64 DEGs, and 32 hub genes were identified, enriched pathways of hub genes involved in several functions and expression pathways, such as complement binding, extracellular matrix structural constituent, complement cascade related pathways, and ECM proteoglycans. The correlation analysis and subgroup analysis of 7 complement cascade-related hub genes and the clinical characteristics of DN showed that C1QA, C1QB, C3, CFB, ITGB2, VSIG4, and CLU may participate in the development of DN. CONCLUSIONS: We confirmed that the complement cascade-related hub genes may be the novel biomarkers for DN early diagnosis and targeted treatment.

Based on Network Pharmacology Tools to Investigate the Molecular Mechanism of Cordyceps sinensis on the Treatment of Diabetic Nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus and is a major cause of end-stage kidney disease. Cordyceps sinensis (Cordyceps, Dong Chong Xia Cao) is a widely applied ingredient for treating patients with DN in China, while the molecular mechanisms remain unclear. This study is aimed at revealing the therapeutic mechanisms of Cordyceps in DN by undertaking a network pharmacology analysis. MATERIALS AND METHODS: In this study, active ingredients and associated target proteins of Cordyceps sinensis were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Swiss Target Prediction platform, then reconfirmed by using PubChem databases. The collection of DN-related target genes was based on DisGeNET and GeneCards databases. A DN-Cordyceps common target interaction network was carried out via the STRING database, and the results were integrated and visualized by utilizing Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the molecular mechanisms and therapeutic effects of Cordyceps on the treatment of DN. RESULTS: Seven active ingredients were screened from Cordyceps, 293 putative target genes were identified, and 85 overlapping targets matched with DN were considered potential therapeutic targets, such as TNF, MAPK1, EGFR, ACE, and CASP3. The results of GO and KEGG analyses revealed that hub targets mainly participated in the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. These targets were correlated with inflammatory response, apoptosis, oxidative stress, insulin resistance, and other biological processes. CONCLUSIONS: Our study showed that Cordyceps is characterized as multicomponent, multitarget, and multichannel. Cordyceps may play a crucial role in the treatment of DN by targeting TNF, MAPK1, EGFR, ACE, and CASP3 signaling and involved in the inflammatory response, apoptosis, oxidative stress, and insulin resistance.