Association Analysis Provides Insights into Plant Mitonuclear Interactions.

Cytonuclear interaction refers to the complex and ongoing process of coevolution between nuclear and organelle genomes, which are responsible for cellular respiration, photosynthesis, lipid metabolism, etc. and play a significant role in adaptation and speciation. There have been a large number of studies to detect signatures of cytonuclear interactions. However, identification of the specific nuclear and organelle genetic polymorphisms that are involved in these interactions within a species remains relatively rare. The recent surge in whole genome sequencing has provided us an opportunity to explore cytonuclear interaction from a population perspective. In this study, we analyzed a total of 3,439 genomes from 7 species to identify signals of cytonuclear interactions by association (linkage disequilibrium) analysis of variants in both the mitochondrial and nuclear genomes across flowering plants. We also investigated examples of nuclear loci identified based on these association signals using subcellular localization assays, gene editing, and transcriptome sequencing. Our study provides a novel perspective on the investigation of cytonuclear coevolution, thereby enriching our understanding of plant fitness and offspring sterility.

Natural products as pharmacological modulators of mitochondrial dysfunctions for the treatment of diabetes and its complications: An update since 2010.

Diabetes, characterized as a well-known chronic metabolic syndrome, with its associated complications pose a substantial and escalating health and healthcare challenge on a global scale. Current strategies addressing diabetes are mainly symptomatic and there are fewer available curative pharmaceuticals for diabetic complications. Thus, there is an urgent need to identify novel pharmacological targets and agents. The impaired mitochondria have been associated with the etiology of diabetes and its complications, and the intervention of mitochondrial dysfunction represents an attractive breakthrough point for the treatments of diabetes and its complications. Natural products (NPs), with multicenter characteristics, multi-pharmacological activities and lower toxicity, have been caught attentions as the modulators of mitochondrial functions in the therapeutical filed of diabetes and its complications. This review mainly summarizes the recent progresses on the potential of 39 NPs and 2 plant-extracted mixtures to improve mitochondrial dysfunction against diabetes and its complications. It is expected that this work may be useful to accelerate the development of innovative drugs originated from NPs and improve upcoming therapeutics in diabetes and its complications.

NDUFB11 and NDUFS3 regulate arterial atherosclerosis and venous thrombosis: Potential markers of atherosclerosis and venous thrombosis.

Atherosclerosis is a chronic disease that thickens the blood vessel walls and narrows the lumen. Venous thrombosis is a blood clot that forms in the body's deep veins or pulmonary arteries. However, the relationship between NDUFB11 and NDUFS3 and atherosclerosis and venous thrombosis is unclear. We employed data files that combined atherosclerosis and chronic stress groups. Subsequently, we conducted differential gene expression analysis (DEGs) and performed weighted gene co-expression network analysis (WGCNA). We constructed and analyzed a protein-protein interaction (PPI) network. Further analyses included functional enrichment analysis, gene set enrichment analysis (GSEA), gene expression heatmaps, immune infiltration analysis, and mRNA analysis. By comparing our findings with the Comparative Toxicogenomics Database (CTD), we identified the most relevant diseases associated with the core genes. Additionally, we utilized TargetScan to screen for miRNAs regulating the central DEGs. To validate our results, we conducted Western Blot experiments at the cellular level. A total of 1747 DEGs were co-identified. According to the Gene Ontology (GO) analysis of differentially expressed genes, they were primarily enriched in mitochondrial gene expression, mitochondrial envelope, organelle membrane, and mitochondrial inner membrane categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target cells were mainly enriched in metabolic pathways, ribosomes, and histidine metabolism. The intersection of enriched terms from both GO and KEGG analyses showed significant enrichment in mitochondrial gene expression, mitochondrial envelope, organelle inner membrane, ribosomal structural constituents, histidine metabolism, and oxidative phosphorylation. Eight core genes were identified, including NDUFS5, UQCRQ, COX6C, COX7B, ATP5ME, NDUFS3, NDUFA3, and NDUFB11. The gene expression heatmap demonstrated that core genes (NDUFB11 and NDUFS3) were downregulated in atherosclerosis with venous thrombosis samples and upregulated in normal samples. CTD analysis revealed that the core genes NDUFB11 and NDUFS3 were associated with pain, arterial diseases, atherosclerosis, arteritis, venous thrombosis formation, and venous thromboembolism. We added Western Blot basic cell experiment for verification. NDUFB11 and NDUFS3 are downregulated in atherosclerosis and venous thrombosis, associated with poorer prognosis, and may serve as potential biomarkers for both diseases.

NDUFB11 and NDUFS3 play a role in atherosclerosis and chronic stress.

OBJECTIVE: Atherosclerosis is characterized by the formation of fibrofatty plaques in the intima of arteries, resulting in thickening of the vessel wall and narrowing of the lumen. Chronic stress refers to individuals in a state of long-term chronic stress. However, the relationship between NDUFB11 and NDUFS3 and atherosclerosis and chronic stress is unclear. METHOD: The atherosclerosis with chronic stress group data file was used. DEGs were screened and WGCNA was performed. Construction and analysis of PPI Network. Functional enrichment analysis, GSEA, gene expression heatmap, immune infiltration analysis and mRNA analysis were performed. CTD was used to find diseases most related to core genes. WB was performed. TargetScan was used to screen miRNAs of DEGs. RESULTS: 1708 DEGs were identified. According to GO analysis, they were mainly enriched in catabolic processes, organic acid metabolism processes, carboxylic acid metabolism processes. KEGG analysis showed that they were mainly enriched in metabolic pathways, fatty acid metabolism, pentose phosphate pathway, glycolysis / gluconeogenesis, fructose and mannose metabolism. Gene expression heatmap showed that the core genes (NDUFB11, NDUFS3) were lowly expressed in samples of those with atherosclerosis accompanied by chronic stress and highly expressed in the normal samples. NDUFB11 and NDUFS3 were associated with necrosis, hyperplasia, inflammation, renal disease, weight loss, memory impairment, and cognitive impairment. WB showed that the expression level of NDUFS3 in atherosclerosis and chronic stress was lower than that in control group. CONCLUSIONS: NDUFB11 and NDUFS3 are underexpressed in atherosclerosis and chronic stress; the lower NDUFB11 and NDUFS3 levels, the worse the prognosis.

Laboratory scoring system to predict hepatic indocyanine green clearance ability during fluorescence imaging-guided laparoscopic hepatectomy.

BACKGROUND: Indocyanine green (ICG) fluorescence played an important role in tumor localization and margin delineation in hepatobiliary surgery. However, the preoperative regimen of ICG administration was still controversial. Factors associated with tumor fluorescence staining effect were unclear. AIM: To investigate the preoperative laboratory indexes corelated with ICG fluorescence staining effect and establish a novel laboratory scoring system to screen specifical patients who need ICG dose adjustment. METHODS: To investigate the predictive indicators of ICG fluorescence characteristics in patients undergoing laparoscopic hepatectomy from January 2018 to January 2021 were included. Blood laboratory tests were completed within 1 wk before surgery. All patients received 5 mg ICG injection 24 h before surgery for preliminary tumor imaging. ImageJ software was used to measure the fluorescence intensity values of regions of interest. Correlation analysis was used to identify risk factors. A laboratory risk model was established to identify individuals at high risk for high liver background fluorescence. RESULTS: There were 110 patients who were enrolled in this study from January 2019 to January 2021. The mean values of fluorescence intensity of liver background (FI-LB), fluorescence intensity of gallbladder, and fluorescence intensity of target area were 18.87 ± 17.06, 54.84 ± 33.29, and 68.56 ± 36.11, respectively. The receiver operating characteristic (ROC) curve showed that FI-LB was a good indicator for liver clearance ability [area under the ROC curve (AUC) = 0.984]. Correlation analysis found pre-operative aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, adenosine deaminase, and lactate dehydrogenase were positively associated with FI-LB and red blood cell, cholinesterase, and were negatively associated with FI-LB. Total laboratory risk score (TLRS) was calculated according to ROC curve (AUC = 0.848, sensitivity = 0.773, specificity = 0.885). When TLRS was greater than 6.5, the liver clearance ability of ICG was considered as poor. CONCLUSION: Preoperative laboratory blood indicators can predict hepatic ICG clearance ability. Surgeons can adjust the dose and timing of ICG preoperatively to achieve better liver fluorescent staining.

Clinicopathological characterization of ten patients with primary malignant melanoma of the esophagus and literature review.

BACKGROUND: Primary malignant melanoma of the esophagus (PMME) is a rare malignant disease and has not been well characterized in terms of clinicopathology and survival. AIM: To investigate the clinical features and survival factors in Chinese patients with PMME. METHODS: The clinicopathological findings of ten cases with PMME treated at Henan Provincial People's Hospital were summarized. Moreover, the English- and Chinese-language literature that focused on Chinese patients with PMME from 1980 to September 2021 was reviewed and analyzed. Univariate and multivariate analyses were employed to investigate the clinicopathologic factors that might be associated with survival. RESULTS: A total of 290 Chinese patients with PMME, including ten from our hospital and 280 from the literature were enrolled in the present study. Only about half of the patients (55.8%) were accurately diagnosed before surgery. Additionally, 91.1% of the patients received esophagectomy, and 88 patients (36.5%) received adjuvant therapy after surgery. The frequency of lymph node metastasis (LNM) was 51.2% (107/209), and LNM had a positive rate of 45.3% even when the tumor was confined to the submucosal layer. The risk of LNM increased significantly with the pT stage [P < 0.001, odds ratio (OR): 2.47, 95% confidence interval (CI): 1.72-3.56] and larger tumor size (P = 0.006, OR: 1.21, 95%CI: 1.05-1.38). The median overall survival (OS) was 11.0 mo (range: 1-204 mo). The multivariate Cox analysis showed both the pT stage [P = 0.005, hazard ratio (HR): 1.70, 95%CI: 1.17-2.47] and LNM (P = 0.009, HR: 1.78, 95%CI: 1.15-2.74) were independent prognostic factors for OS. The median disease-free survival (DFS) was 5.3 mo (range: 0.8-114.1 mo). The multivariate analysis indicated that only the advanced pT stage (P = 0.02, HR: 1.93, 95%CI: 1.09-3.42) was a significant independent indicator of poor RFS in patients with PMME. CONCLUSION: The correct diagnosis of PMME before surgery is low, and physicians should pay more attention to avoid a misdiagnosis or missed diagnosis. Extended lymph node dissection should be emphasized in surgery for PMME even though the tumor is confined to the submucosal layer. Both the LNM and pT stage are independent prognosis factors for OS, and the pT stage is the prognosis factor for DFS in patients with PMME.

The mediating function of obesity on endocrine-disrupting chemicals and insulin resistance in children.

OBJECTIVES: To explore the association of endocrine-disrupting chemicals (EDCs) with insulin resistance (IR) in children as well as whether obesity played a mediation role between EDCs and IR. METHODS: In this cross-sectional study, the data of 878 subjects were included, and divided into the non-IR group (n=501) and IR group (n=377). The associations of EDC and IR, obesity, abdominal obesity were shown by restricted cubic spline (RCS). Univariate and multivariable logistic analysis were applied to explore the associations between EDCs and IR as well as EDCs and obesity, respectively. Bootstrap coefficient product was used to analyze the medication effect of obesity on EDCs and IR. RESULTS: RCS showed that increase of benzophenone-3 (BP-3) level was associated with increased risk of IR, obesity and abdominal obesity. After adjusting for confounders, BP-3>100 ng/mL was a risk factor for IR (OR=1.42, 95%CI: 1.11-1.81). In the adjusted model, we found BP-3>100 ng/mL was a risk factor for both obesity (OR=1.52, 95%CI: 1.13-2.04) and abdominal obesity (OR=1.68, 95%CI: 1.11-2.54). The indirect effect of obesity as a mediator on the relationship between BP-3 and IR was 0.038 (95%CI: 0.016-0.090) and the direct effect of obesity as a mediator on the relationship between BP-3 and IR was 0.077 (95%CI: 0.001-0.160). As for abdominal obesity, the indirect effect of it on the relationship between BP-3 and IR was 0.039 (95%CI: 0.007-0.070). CONCLUSIONS: BP-3 level might be a risk factor for IR and obesity in children, and obesity was a mediator on the relationship between BP-3 and IR in children.

Identification of a seven-cell cycle signature predicting overall survival for gastric cancer.

While genetic alterations in several regulators of the cell cycle have a significant impact on the gastric carcinogenesis process, the prognostic role of them remains to be further elucidated. The TCGA-STAD training set were downloaded and the mRNA expression matrix of cell cycle genes was extracted and corrected for further analysis after taking the intersection with GSE84437 dataset. Differentially expressed mRNAs were identified between tumor and normal tissue samples in TCGA-STAD. Univariate Cox regression analysis and lasso Cox regression model established a novel seven-gene cell cycle signature (including GADD45B, TFDP1, CDC6, CDC25A, CDC7, SMC1A and MCM3) for GC prognosis prediction. Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group. The signature was found to be an independent prognostic factor for GC survival. Nomogram including the signature shown some clinical net benefit for overall survival prediction. The signature was further validated in the GSE84437 dataset. In tissue microarray, CDC6 and MCM3 protein expression were significant differences by the immunohistochemistry-based H-score between tumor tissues and adjacent tissues, and CDC6 is an independent prognostic factor for GC. Interestingly, our GSEA revealed that low-risk patients were more related to cell cycle pathways and might benefit more from therapies targeting cell cycle. Our study identified a novel robust seven-gene cell cycle signature for GC prognosis prediction that may serve as a beneficial complement to clinicopathological staging. The signature might provide potential biomarkers for the application of cell cycle regulators to therapies and treatment response prediction.

Transcriptomics Reveals the Effect of Thymol on the Growth and Toxin Production of Fusarium graminearum.

Fusarium graminearum is a harmful pathogen causing head blight in cereals such as wheat and barley, and thymol has been proven to inhibit the growth of many pathogens. This study aims to explore the fungistatic effect of thymol on F. graminearum and its mechanism. Different concentrations of thymol were used to treat F. graminearum. The results showed that the EC50 concentration of thymol against F. graminearum was 40 µg/mL. Compared with the control group, 40 µg/mL of thymol reduced the production of Deoxynivalenol (DON) and 3-Ac-DON by 70.1% and 78.2%, respectively. Our results indicate that thymol can effectively inhibit the growth and toxin production of F. graminearum and cause an extensive transcriptome response. Transcriptome identified 16,727 non-redundant unigenes and 1653 unigenes that COG did not annotate. The correlation coefficients between samples were all >0.941. When FC was 2.0 times, a total of 3230 differential unigenes were identified, of which 1223 were up-regulated, and 2007 were down-regulated. Through the transcriptome, we confirmed that the expression of many genes involved in F. graminearum growth and synthesis of DON and other secondary metabolites were also changed. The gluconeogenesis/glycolysis pathway may be a potential and important way for thymol to affect the growth of F. graminearum hyphae and the production of DON simultaneously.

Awareness for Endoscopic Screening Among Accompanying Children of Hospitalized Esophageal Cancer Patients in Henan.

The free generalized endoscopic screening for diagnosis of early esophageal cancer and precancerous lesion could not be satisfactorily implemented in China. At present, the decision to accept endoscopic screening at their own expense may largely depend on the public awareness. This study was aimed to investigate the awareness and other influencing factors associated with the accompanying children of esophageal cancer patients after their hospitalization. In this cross-sectional study, from April to June 2016, 233 children of accompanying patients, who were admitted within the last 1 year due to esophageal cancer in three affiliated hospitals of Zhengzhou University and Anyang Tumor Hospital, were enrolled. In addition, telephone surveys were conducted to investigate their awareness about endoscopic screening. One child was corresponded to an esophageal cancer patient. About half (47.6%, 111/233) of the children were unaware that endoscopic screening could detect early esophageal cancer and precancerous lesion. There was no significant difference in their awareness rates between hospitals with different administration levels. Besides, the males who had a lower family income and lower education level showed a poor awareness rate (P < 0.05). The overall awareness rate among the accompanying children of patients on endoscopic screening was rather low in Henan province (China). Hence, the health education and awareness on the importance of endoscopic screening for early detection of esophageal cancer should be promoted among children accompanying the patients. More attention should be focused towards the subject group, particularly among those male children with lower educational level and family income.

Genome-wide screening and identification of nuclear Factor-Y family genes and exploration their function on regulating abiotic and biotic stress in potato (Solanum tuberosum L.).

The Nuclear Factor-Y (NF-Y) transcription factor (TF), which includes three distinct subunits (NF-YA, NF-YB and NF-YC), is known to manipulate various aspects of plant growth, development, and stress responses. Although the NF-Y gene family was well studied in many species, little is known about their functions in potato. In this study, a total of 37 potato NF-Y genes were identified, including 11 StNF-YAs, 20 StNF-YBs, and 6 StNF-YCs. The genetic features of these StNF-Y genes were investigated by comparing their evolutionary relationship, intron/exon organization and motif distribution pattern. Multiple alignments showed that all StNF-Y proteins possessed clearly conserved core regions that were flanked by non-conserved sequences. Gene duplication analysis indicated that nine StNF-Y genes were subjected to tandem duplication and eight StNF-Ys arose from segmental duplication events. Synteny analysis suggested that most StNF-Y genes (33 of 37) were orthologous to potato's close relative tomato (Solanum lycopersicum L.). Tissue-specific expression of the StNF-Y genes suggested their potential roles in controlling potato growth and development. The role of StNF-Ys in regulating potato responses to abiotic stress (ABA, drought and salinity) was also confirmed: twelve StNF-Y genes were up-regulated and another two were down-regulated under different abiotic treatments. In addition, genes responded differently to pathogen challenges, suggesting that StNF-Y genes may play distinct roles under certain biotic stress. In summary, insights into the evolution of NF-Y family members and their functions in potato development and stress responses are provided.

[History of Superior Oblique Muscle Surgery].

The superior oblique muscle has the longest tendon among the six extraocular muscles and serves complex functions. Surgery on the superior oblique muscle is considered the most complicated and difficult procedure in the field of strabismus. This article focuses on the history of superior oblique muscle surgeries, including superior oblique weakening procedure and superior oblique strengthening procedure. We discussed the advantages, disadvantages, and indications of each type of surgery, providing colleagues in the field of ophthalmology with a comprehensive understanding of superior oblique muscle surgery and facilitating the carefully weighed decision to choose and perform the procedure.

A systems genetics approach reveals PbrNSC as a regulator of lignin and cellulose biosynthesis in stone cells of pear fruit.

BACKGROUND: Stone cells in fruits of pear (Pyrus pyrifolia) negatively influence fruit quality because their lignified cell walls impart a coarse and granular texture to the fruit flesh. RESULTS: We generate RNA-seq data from the developing fruits of 206 pear cultivars with a wide range of stone cell contents and use a systems genetics approach to integrate co-expression networks and expression quantitative trait loci (eQTLs) to characterize the regulatory mechanisms controlling lignocellulose formation in the stone cells of pear fruits. Our data with a total of 35,897 expressed genes and 974,404 SNPs support the identification of seven stone cell formation modules and the detection of 139,515 eQTLs for 3229 genes in these modules. Focusing on regulatory factors and using a co-expression network comprising 39 structural genes, we identify PbrNSC as a candidate regulator of stone cell formation. We then verify the function of PbrNSC in regulating lignocellulose formation using both pear fruit and Arabidopsis plants and further show that PbrNSC can transcriptionally activate multiple target genes involved in secondary cell wall formation. CONCLUSIONS: This study generates a large resource for studying stone cell formation and provides insights into gene regulatory networks controlling the formation of stone cell and lignocellulose.

The Potential Role of Osteopontin in the Pathogenesis of Graves' Ophthalmopathy.

Purpose: The aim of this study is to evaluate the expression of osteopontin (OPN) and its relationship with relative cytokines in patients with Graves' ophthalmopathy (GO), and to observe the effect of OPN on orbital fibroblasts (OFs) proliferation, migration, and the expression of relative cytokines, as well as the signaling pathways involved in its effect. Methods: The orbital adipose connective tissue was obtained from 24 patients with GO (12 cases of active GO, and 12 cases of inactive GO) and 12 healthy controls. OFs were isolated from orbital tissues obtained from patients with active GO who were undergoing orbital decompression surgery. Quantitative PCR and Western blot were performed to detect RNA and protein expression. The proliferation and cell migration rates of OFs were measured by methylthiazol tetrazolium (MTT) and the cell scratch test. Signaling pathway inhibitors, such as OPN monoclonal antibody 1A12, ERK1/2 inhibitor PD98059, and PI3K inhibitor LY294002, were applied to determine the involved pathways. Results: The mRNA and protein levels of OPN were increased in orbital adipose connective tissue from patients with active GO than those from patients with inactive GO (2.83-fold increase, P < 0.001; 1.91-fold increase, P < 0.05). The OPN mRNA level was positively correlated with CD40 ligand (CD40L) and hyaluronan synthases 2 (HAS2) mRNA in patients with GO. OPN promoted proliferation and migration rate of OFs and induced vascular endothelial growth factor (VEGF) and collagen I mRNA expression, and the effects were inhibited by 1A12 or LY294002. Conclusions: OPN in orbital adipose connective tissues were significantly increase in active GO, and there were significant correlations of OPN with CD40L and HAS2 mRNA levels in patients with GO. OPN promoted proliferation and migration of OFs and induced VEGF and collagen I mRNA expression in OFs through PI3K/Akt signaling pathway. This suggested a role for OPN in the pathogenesis of GO through the activation of OFs.

Tanshinone IIA Combined With Cyclosporine A Alleviates Lung Apoptosis Induced by Renal Ischemia-Reperfusion in Obese Rats.

Acute lung injury (ALI), which is induced by renal ischemia-reperfusion (IR), is one of the leading causes of acute renal IR-related death. Obesity raises the frequency and severity of acute kidney injury (AKI) and ALI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) was employed to lessen the lung apoptosis led by renal IR and to evaluate whether TIIA combined with CsA could alleviate lung apoptosis by regulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats. Hematoxylin-eosin (HE) staining was used to assess the histology of the lung injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was used to assess apoptosis of the lung. Electron microscopy was used to assess mitochondrial morphology in lung cells. Arterial blood gas and pulmonary function were used to assess the external respiratory function. Mitochondrial function was used to assess the internal respiratory function and mitochondrial dynamics and biogenesis. Western blot (WB) was used to examine the PI3K/Akt/Bad pathway-related proteins. TIIA combined with CsA can alleviate lung apoptosis by regulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.

Tanshinone IIA combined with CsA inhibit myocardial cell apoptosis induced by renal ischemia-reperfusion injury in obese rats.

BACKGROUND: Acute myocardial injury (AMI), which is induced by renal ischemia-reperfusion (IR), is a significant cause of acute kidney injury (AKI)-related associated death. Obesity increases the severity and frequency of AMI and AKI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) pretreatment was used to alleviate myocardial cell apoptosis induced by renal IR, and to determine whether TIIA combined with CsA would attenuate myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats. METHODS: Male rates were fed a high fat diet for 8 weeks to generate obesity. AKI was induced by 30 min of kidney ischemia followed 24 h of reperfusion. Obese rats were given TIIA (10 mg/kg·d) for 2 weeks and CsA (5 mg/kg) 30 min before renal IR. After 24 h of reperfusion, the rats were anaesthetized, the blood were fetched from the abdominal aorta and kidney were fetched from abdominal cavity, then related indicators were examined. RESULTS: TIIA combined with CsA can alleviate the pathohistological injury and apoptosis induced by renal IR in myocardial cells. TIIA combined with CsA improved cardiac function after renal ischemia (30 min)-reperfusion (24 h) in obese rats. At the same time, TIIA combined with CsA improved mitochondrial function. Abnormal function of mitochondria was supported by decreases in respiration controlling rate (RCR), intracellular adenosine triphosphate (ATP), oxygen consumption rate, and mitochondrial membrane potential (MMP), and increases in mitochondrial reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore (mPTP), mitochondrial DNA damage, and mitochondrial respiratory chain complex enzymes. The injury of mitochondrial dynamic function was assessed by decrease in dynamin-related protein 1 (Drp1), and increases in mitofusin1/2 (Mfn1/2), and mitochondrial biogenesis injury was assessed by decreases in PPARγ coactivator-1-α (PGC-1), nucleo respiratory factor1 (Nrf1), and transcription factor A of mitochondrial (TFam). CONCLUSION: We used isolated mitochondria from rat myocardial tissues to demonstrate that myocardial mitochondrial dysfunction occurred along with renal IR to induce myocardial cell apoptosis; obesity aggravated apoptosis. TIIA combined with CsA attenuated myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.

Vascular Endothelial Function as a Valid Predictor of Variations in Pulmonary Function in T2DM Patients Without Related Complications.

To assess the variations in pulmonary function and vascular endothelial function in their early stages (without related complications). A total of 162 type 2 diabetes mellitus (T2DM) patients without diabetes complications and 55 healthy people were selected, comprising the T2DM group and the control group, respectively, to evaluate changes in vascular endothelial function and lung function and determine the correlation between them. In this study, the T2DM group exhibited significantly lower pulmonary function than that of the control group (P < 0.05). The T2DM group also showed significantly lower flow-mediated dilation (FMD) and nitric oxide (NO) (P < 0.05) than those of the control group. Pulmonary functional indexes correlated positively with FMD and NO (P < 0.05) and correlated negatively with endothelin-1 (ET-1) (P < 0.05). FMD and NO correlated negatively with diabetes duration/HbA1c (P < 0.05), whereas ET-1 correlated positively with glycosylated hemoglobinA1c (HbA1c)/diabetes duration (P < 0.05). Pulmonary functional indexes negatively correlated with HbA1c/diabetes duration (P < 0.05). Multiple linear regression was used to analyze the relationship between vascular endothelial function indexes (FMD, ET-1, and NO) and pulmonary functional indexes. The results indicated that each vascular endothelial function index (FMD, ET-1, and NO) was significantly correlated with the pulmonary functional index (P < 0.05). The patients with T2DM presented changes in the subclinical vascular endothelial and pulmonary function. They also had impaired vascular endothelial functions, which were characterized by reduced vascular endothelial function relative to those of healthy people. Regulating glycemia may improve vascular endothelial and pulmonary functions. Moreover, microvascular lesions in preclinical stages, vascular endothelial function indexes (FMD, ET-1, and NO) were valid predictors of alterations in pulmonary function in T2DM patients without related complications. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03575988.

QTLs and candidate genes analyses for fruit size under domestication and differentiation in melon (Cucumis melo L.) based on high resolution maps.

BACKGROUND: Melon is a very important horticultural crop produced worldwide with high phenotypic diversity. Fruit size is among the most important domestication and differentiation traits in melon. The molecular mechanisms of fruit size in melon are largely unknown. RESULTS: Two high-density genetic maps were constructed by whole-genome resequencing with two F2 segregating populations (WAP and MAP) derived from two crosses (cultivated agrestis × wild agrestis and cultivated melo × cultivated agrestis). We obtained 1,871,671 and 1,976,589 high quality SNPs that show differences between parents in WAP and MAP. A total of 5138 and 5839 recombination events generated 954 bins in WAP and 1027 bins in MAP with the average size of 321.3 Kb and 301.4 Kb respectively. All bins were mapped onto 12 linkage groups in WAP and MAP. The total lengths of two linkage maps were 904.4 cM (WAP) and 874.5 cM (MAP), covering 86.6% and 87.4% of the melon genome. Two loci for fruit size were identified on chromosome 11 in WAP and chromosome 5 in MAP, respectively. An auxin response factor and a YABBY transcription factor were inferred to be the candidate genes for both loci. CONCLUSION: The high-resolution genetic maps and QTLs analyses for fruit size described here will provide a better understanding the genetic basis of domestication and differentiation, and provide a valuable tool for map-based cloning and molecular marker assisted breeding.

Developing a new model system for potato genetics by androgenesis.

High heterozygosity and tetrasomic inheritance complicate studies of asexually propagated polyploids, such as potato. Reverse genetics approaches, especially mutant library construction, can be an ideal choice if a proper mutagenesis genotype is available. Here, we aimed to generate a model system for potato research using anther cultures of Solanum verrucosum, a self-compatible diploid potato with strong late blight resistance. Six of the 23 regenerants obtained (SVA4, SVA7, SVA22, SVA23, SVA32, and SVA33) were diploids, and their homozygosity was estimated to be >99.99% with 22 polymorphic InDel makers. Two lines-SVA4 and SVA32-had reduced stature (plant height ≤80 cm), high seed yield (>1,000 seeds/plant), and good tuber set (>30 tubers/plant). We further confirmed the full homozygosity of SVA4 and SVA32 using whole-genome resequencing. These two regenerants possess all the characteristics of a model plant: diploidy, 100% homozygosity, self-compatibility, and amenability to transgenesis. Thus, we have successfully generated two lines, SVA4 and SVA32, which can potentially be used for mutagenesis and as model plants to rejuvenate current methods of conducting potato research.

Genomic analyses of diverse wild and cultivated accessions provide insights into the evolutionary history of jujube.

The Chinese jujube (Ziziphus jujuba Mill.), a member of the Rhamnaceae family, is an important perennial fruit tree crop of substantial economic, ecological and nutritional value, and is also used as a traditional herbal medicine. Here, we report the resequencing of 493 jujube accessions, including 202 wild and 291 cultivated accessions at >16× depth. Our population genomic analyses revealed that the Shanxi-Shaanxi area of China was jujube's primary domestication centre and that jujube was then disseminated into East China before finally extending into South China. Divergence events analysis indicated that Ziziphus acidojujuba and Ziziphus jujuba diverged around 2.7 Mya, suggesting the interesting possibility that a long pre-domestication period may have occurred prior to human intervention. Using the large genetic polymorphism data set, we identified a 15-bp tandem insertion in the promoter of the jujube ortholog of the POLLEN DEFECTIVE IN GUIDANCE 1 (POD1) gene, which was strongly associated with seed-setting rate. Integrating genome-wide association study (GWAS), transcriptome data, expression analysis and transgenic validation in tomato, we identified a DA3/UBIQUITIN-SPECIFIC PROTEASE 14 (UBP14) ortholog, which negatively regulate fruit weight in jujube. We also identified candidate genes, which have likely influenced the selection of fruit sweetness and crispness texture traits among fresh and dry jujubes. Our study not only illuminates the genetic basis of jujube evolution and domestication and provides a deep and rich genomic resource to facilitate both crop improvement and hypothesis-driven basic research, but also identifies multiple agriculturally important genes for this unique perennial tree fruit species.