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Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus. The most common type is distal symmetric polyneuropathy, and lesions frequently lead to disabling neuropathic pain and even amputation, increasing the risk of death. At present, the pathogenesis of DPN has not been clarified, and its insidious onset and lack of obvious symptoms in most patients in the early stages often lead to delayed diagnosis, which is unfavourable for prevention and treatment. This article provides an overview of the existing research progress on early diagnostic markers of DPN, especially oxidative stress-related markers, neural tissue damage markers, inflammation-related markers, neurovascular damage markers, and gene-related markers, in the hope that it can provide a reference for early diagnosis and treatment of DPN, and slow down the occurrence and development of DPN.

Powdery mildew (PM), caused by the biotrophic fungus Podospharea leucotricha , poses a significant threat to apple production. Salicylic acid (SA) signaling plays a crucial role in enhancing resistance to biotrophic pathogens. While PR1, a defense protein induced by SA, is essential for plant immunity, its excessive accumulation can be detrimental. However, the mechanism of PR1-mediated immune balance remains unclear. This study identified a key transcription factor, WRKY1, which enhances the SA accumulation by modulating the SA biosynthesis gene EPS1 , while simultaneously regulating the WRKY40-NPR3g module to prevent sustained PR1 expression caused by continuous SA accumulation. Specifically, the transcription factor WRKY40 upregulates NPR3g expression, and NPR3g interacts with NPR1 in an SA-dependent manner. Then, two TGA2c variants that interact with NPR1 to activate PR1 expression were identified: canonical TGA2c-1 and alternative splicing of TGA2c-2 with an exon deletion. SA does not influence the NPR1-TGA2c-1 interaction but is essential for the NPR1-TGA2c-2 interaction. Notably, NPR3g reduces PR1 levels by selectively disrupting the NPR1-TGA2c-2 complex through competition for the BTB-POZ domain of NPR1. In conclusion, this study identifies a novel mechanism by which WRKY1 modulates PR1-mediated immune balance to defend against PM.

As a fruit tree with great economic value, apple is widely cultivated in China. However, apple leaf spot disease causes significant damage to apple quality and economic value. In our study, we found that MdMYB6-like is a transcription factor without auto-activation activity and with three alternative spliced variants. Among them, MdMYB6-like-β responded positively to the pathogen infection. Overexpression of MdMYB6-like-β increased the lignin content of leaves and improved the pathogenic resistance of apple flesh callus. In addition, all three alternative spliced variants of MdMYB6-like could bind to the promoter of MdBGLU H. Therefore, we believe that MdMYB6-like plays an important role in the infection process of the pathogen and lays a solid foundation for breeding disease-resistant cultivars of apple in the future.

Alternaria blotch disease, caused by the Alternaria alternata apple pathotype (A. alternata AP), is one of the most serious fungal diseases in apples. Alternative splicing (AS), one of the pivotal post-transcriptional regulatory mechanisms, plays essential roles in various disease resistance responses. Here, we performed RNA-Seq for two apple cultivars (resistant cultivar ‘Jonathan’ (J) and susceptible cultivar ‘Starking Delicious’ (SD)) infected by A. alternata AP to further investigate their AS divergence. In total, 1454, 1780, 1367 and 1698 specifically regulated differential alternative splicing (DAS) events were detected in J36, J72, SD36 and SD72 groups, respectively. Retained intron (RI) was the dominant AS pattern. Conformably, 642, 764, 585 and 742 uniquely regulated differentially spliced genes (DSGs) were found during A. alternata AP infection. Comparative analysis of AS genes in differential splicing and expression levels suggested that only a small proportion of DSGs overlapped with differentially expressed genes (DEGs). Gene ontology (GO) enrichment analysis demonstrated that the DSGs were significantly enriched at multiple levels of gene expression regulation. Briefly, the specific AS was triggered in apple defense against A. alternata AP. Therefore, this study facilitates our understanding on the roles of AS regulation in response to A. alternata AP infection in apples.

As a fruit tree with great economic value, apple is widely cultivated in China. However, apple leaf spot disease causes significant damage to apple quality and economic value. In our study, we found that MdMYB6-like is a transcription factor without auto-activation activity and with three alternative spliced variants. Among them, MdMYB6-like-β responded positively to the pathogen infection. Overexpression of MdMYB6-like-β increased the lignin content of leaves and improved the pathogenic resistance of apple flesh callus. In addition, all three alternative spliced variants of MdMYB6-like could bind to the promoter of MdBGLU H. Therefore, we believe that MdMYB6-like plays an important role in the infection process of the pathogen and lays a solid foundation for breeding disease-resistant cultivars of apple in the future.

AimsReactivation of embryonic ζ-globin is a promising strategy for genetic treatment of α-thalassaemia. However, quantification of ζ-globin as a quantitative trait in α-thalassaemia carriers and patients remains incompletely understood. In this study, we aimed to set up a reliable approach for the quantification of ζ-globin in α-thalassaemia carriers, followed by a population study to investigate its expression patterns.Methodsζ-globin was purified as monomers from cord blood haemolysate of a Hb Bart’s fetus, followed by absolute protein quantification, which was then tested by in-house ELISA system and introduced as protein standard. It was then used for large-scale quantification in peripheral blood samples from 6179 individuals. Finally, liquid chromatography-tandem mass spectrometry (LC-MS/MS) introduced as an independent validating approach by measuring ζ-globin expression in a second cohort of 141-SEA/αα carriers.ResultsThe ELISA system was proved sensitive in distinguishing individuals with varied extent of ζ-globin. Large scale quantitative study of this --SEA/αα carrier cohort indicated the high diversity of ζ-globin expression ranging from 0.00155 g/L to 1.48778 g/L. Significant positive correlation between ELISA and LC-MS/MS (R=0.400, p<0.001) was observed and it is more sensitive in distinguishing the samples with extreme expression of ζ-globin (R=0.650, p<0.001).ConclusionOur study has reported reliable approaches for the quantification of ζ-globin and presented the expression patterns of ζ-globin among the --SEA/αα carrier population, which might lay a foundation on subsequent genotype–phenotype studies on mechanisms of delayed haemoglobin switch in α-thalassaemia.

The effect of soil nutrient content on fruit yield and fruit quality is very important. To explore the effect of soil nutrients on apple quality we investigated 200 fruit samples from 40 orchards in Feng County, Jiangsu Province. Soil mineral elements and fruit quality were measured. The effect of soil nutrient content on fruit quality was analyzed by artificial neural network (ANN) model. The results showed that the prediction accuracy was highest (R2 = 0.851, 0.847, 0.885, 0.678 and 0.746) in mass per fruit (MPF), hardness (HB), soluble solids concentrations (SSC), titratable acid concentration (TA) and solid-acid ratio (SSC/TA), respectively. The sensitivity analysis of the prediction model showed that soil available P, K, Ca and Mg contents had the greatest impact on the quality of apple fruit. Response surface method (RSM) was performed to determine the optimum range of the available P, K, Ca, and Mg contents in orchards In Feng County, which were 10∼20 mg⋅kg−1, 170∼200 mg⋅kg−1, 1000∼1500 mg⋅kg−1, and 80∼200 mg⋅kg−1, respectively. The research also concluded that improving the content of available P and available Ca in orchard soil was crucial to improve apple fruit quality in Feng County, Jiangsu Province.

Long non-coding RNAs (lncRNAs) are important mediators of the initiation and progression of tumors, including breast cancer (BC). The exact role of long intergenic non-coding RNA 00312 (LINC00312) in BC and its mechanism of action have not been reported to date. In the present study, LINC00312 was found to be downregulated in human BC tissues and cell lines by RT-qPCR. The findings of a functional study indicated that overexpression of LINC00312 suppressed the proliferation, colony forming ability, migration and invasiveness of BC cell lines. Mechanistically, LINC00312 was found to induce suppression of cell migration and invasion by directly binding to miR-9. Overexpression of LINC00312 increased the expression of cadherin 1 (CDH1), a direct target of miR-9, and decreased the expression of vimentin (VIM), a major cytoskeletal component of mesenchymal cells as determined by western blot analysis. miR-9 partly abrogated the upregulation of CDH1 and downregulation of VIM induced by LINC00312. Taken together, the results of the present study indicate a role for the LINC00312/miR-9/CDH1 axis in the progression of BC, and suggest a novel lncRNA-based diagnostic biomarker or therapeutic target for BC.

Background Although both preclinical and clinical studies have shown the great application potential of MSCs (mesenchymal stem/stromal cells) in treating many kinds of diseases, therapeutic inconsistency resulting from cell heterogeneity is the major stumbling block to their clinical applications. Cell population diversity and batch variation in the cell expansion medium are two major inducers of MSC heterogeneity. Methods Cell population diversity was investigated through single-cell RNA sequencing analysis of human MSCs derived from the umbilical cord and expanded with fully chemically defined medium in the current study. Then, the MSC subpopulation with enhanced anti-inflammatory effects was studied in vitro and in vivo. Results Our data showed that MSCs contain different populations with different functions, including subpopulations with enhanced functions of exosome secretion, extracellular matrix modification and responses to stimuli (regeneration and immune response). Among them, CD317 + MSCs have improved differentiation capabilities and enhanced immune suppression activities. Underlying mechanism studies showed that higher levels of TSG6 confer enhanced anti-inflammatory functions of CD317 + MSCs. Conclusions Thus, CD317 + MSCs might be a promising candidate for treating immunological disorder-related diseases.

Glioma is characterized by high heterogeneity and poor prognosis. Attempts have been made to understand its diversity in both genetic expressions and radiomic characteristics, while few integrated the two omics in predicting survival of glioma. This study was intended to investigate the connection between glioma imaging and genome, and examine its predictive value in glioma mortality risk and tumor immune microenvironment (TIME). Clinical, transcriptomics and radiomics data were obtained from public datasets and patients in our center. Correlation analysis between gene expression and radiomic feature (RF) was performed, followed by survival analysis to select RF-related genes (RFRGs) and gene expression-related RFs (GRRFs). After that, RFRGs and GRRFs were used to construct mortality risk prediction model of all glioma and isocitrate dehydrogenase (IDH) wild type (WT) glioma. The association between RFRGs and TIME was explored. Six cohorts composed of 1,754 glioma patients were included. Thirty-five genes and eighty-two RFs demonstrated high correlation with each other. Gene score based on RFRGs was independent predictor of both glioma ( P < 0.05) and IDH-WT glioma ( P < 0.05). Same score based on GRRFs was also able to stratify risk of both glioma ( P < 0.0001) and IDH-WT glioma ( P < 0.0001), with nomograms constructed separately. The TIME of gliomas predicted with RFRGs’ score found mismatched risk of death with immune response. RFRGs and GRRFs were able to predict glioma mortality risk and TIME. Further studies could validate our results and explore this genome-imaging interactions.