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Soybean rust (SBR), caused by an obligate biotrophic pathogen Phakopsora pachyrhizi, is a devastating disease of soybean worldwide. However, the mechanisms underlying plant invasion by P. pachyrhizi are poorly understood, which hinders the development of effective control strategies for SBR. Here we performed detailed histological characterization on the infection cycle of P. pachyrhizi in soybean and conducted a high-resolution transcriptional dissection of P. pachyrhizi during infection. This revealed P. pachyrhizi infection leads to significant changes in gene expression with 10 co-expressed gene modules, representing dramatic transcriptional shifts in metabolism and signal transduction during different stages throughout the infection cycle. Numerous genes encoding secreted protein are biphasic expressed, and are capable of inhibiting programmed cell death triggered by microbial effectors. Notably, three co-expressed P. pachyrhizi apoplastic effectors (PpAE1, PpAE2, and PpAE3) were found to suppress plant immune responses and were essential for P. pachyrhizi infection. Double-stranded RNA coupled with nanomaterials significantly inhibited SBR infection by targeting PpAE1, PpAE2, and PpAE3, and provided long-lasting protection to soybean against P. pachyrhizi. Together, this study revealed prominent changes in gene expression associated with SBR and identified P. pachyrhizi virulence effectors as promising targets of RNA interference-based soybean protection strategy against SBR.
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BACKGROUND AND OBJECTIVES: To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in postmenopausal elderly women with type 2 diabetes mellitus (T2DM). METHODS AND STUDY DESIGN: A total of 141 postmenopausal elderly women with T2DM was divided into OP and normal bone mineral density (BMD) groups, the differences in GRNI levels between the two groups were compared. According to the tertile levels of GRNI, T2DM were divided into three groups (T1, T2, T3 groups), and the differences in OP prevalence and levels of BMD among the three groups were compared. RESULTS: Among postmenopausal elderly women with T2DM, GNRI levels were lower in the OP group compared to the nor-mal BMD group [(103±5.46) vs. (105±5.46), p<0.05)]. With elevated GNRI levels, the BMD levels of femoral, total hip, total body, and lumbar vertebrae (L) were gradually increased, which were higher in the T3 group than in the T1 group (all p< 0.05). GNRI levels were positively correlated with the BMD levels of femoral, spine, total hip, total body, L1, L2, L3, L4, and L1-L4. GNRI was an independent influencing factor for the occurrence of OP (OR=0.887, 95%CI [0.795,0.988]). The ROC curve showed that the GNRI combined with serum ALP and P levels had a high predictive value for OP, with an area under the curve of 0.725 (p<0.01). CONCLUSIONS: In postmenopausal elderly women with T2DM, GNRI was independently and positively correlated with BMD levels. GNRI may be a predictor development of OP.
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Densidad Ósea , Diabetes Mellitus Tipo 2 , Posmenopausia , Humanos , Femenino , Anciano , Factores de Riesgo , Estado Nutricional , Evaluación Geriátrica/métodos , Evaluación Geriátrica/estadística & datos numéricos , Osteoporosis Posmenopáusica , Persona de Mediana Edad , Evaluación Nutricional , Anciano de 80 o más Años , OsteoporosisRESUMEN
Nephrogenic diabetes insipidus (NDI) is a rare genetic disorder primarily associated with mutations in the arginine vasopressin receptor 2 (AVPR2) gene or the aquaporin 2 (AQP2) gene, resulting in impaired water reabsorption in the renal tubules. This report describes a case of a young male patient with NDI from China with a history of polydipsia and polyuria for over 15 years. Laboratory examinations of the proband indicated low urine-specific gravity and osmolality. Urologic ultrasound revealed severe bilateral hydronephrosis in both kidneys, bilateral dilatation of the ureters, roughness of the bladder wall, and the formation of muscle trabeculae. The diagnosis of diabetes insipidus was confirmed by water deprivation tests. The administration of posterior pituitary hormone did not alter urine-specific gravity, and osmolality remained at a low level (<300 mOsm/kg). Based on these findings, and the genetic tests of the proband and his parents were performed. A missense mutation (c.616 G>C) in exon 3 of the AVPR2 gene of the proband was found, caused by the substitution of amino acid valine to leucine at position 206 [p.Val206Leu], which was a hemizygous mutation and consistent with X-chromosome recessive inheritance. The administration of oral hydrochlorothiazide improves the symptoms of polydipsia and polyuria in the proband. This novel AVPR2 gene mutation may be the main cause of NDI in this family, which induces a functional defect in AVPR2, and leads to reduced tubular reabsorption of water.
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Background: Atrophic scarring is a severe form-disfiguring sequela of acne, which can lead to negative effect on patients' life. Fractional microplasma radiofrequency (RF) has emerged as a promising modality, leveraging dermal fibroblast remodeling to enhance aesthetic results for scars and hyperpigmentation. This study evaluates the efficacy and safety of high-power fractional microplasma RF for atrophic acne scars, considering patient tolerance to procedural discomfort. Methods: In this prospective study, 95 Chinese patients with atrophic facial acne scars underwent three sessions of fractional microplasma RF treatment, with assessments at 1, 3, and 6 months post-treatment. Patients were categorized based on treatment power: Group A (50-70 W) and Group B (70-85 W). Efficacy was determined by three independent dermatologists using digital photographs and Echelle d'Evaluation Clinique des Cicatrices d'Acné (ECCA) scores, and patient-reported outcomes gauged satisfaction levels. Results: Eighty-six patients completed the study. Significant improvements were observed, with a reduction in ECCA scores from 107.21 to 42.27 (P<0.05), demonstrating notable scar amelioration across both groups, albeit with a superior outcome in Group B. All patients experienced transient side effects such as pain, erythema, and edema, deemed tolerable with no long-term adverse effects reported. The treatment was well-received, with high satisfaction rates, underscoring its efficacy and acceptable safety profile. Conclusion: Fractional microplasma RF therapy, particularly at higher power settings, is an effective and safe option for treating atrophic acne scars, offering significant aesthetic improvement with manageable discomfort. This modality presents a valuable addition to acne scar management strategies, especially for patients with darker skin tones seeking minimal downtime and reduced risk of hyperpigmentation.
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To assess the possibility of using aerobic denitrification (AD) bacteria with high NO2--N accumulation for nitrogen removal in wastewater treatment, conditional optimization, as well as sole and mixed nitrogen source tests involving AD bacterium, Comamonas sp. pw-6 was performed. The results showed that the optimal carbon source, pH, C/N ratio, rotational speed, and salinity for this strain were determined to be succinate, 7, 20, 160 rpm, and 0%, respectively. Further, this strain preferentially utilized NH4+-N, NO3--N, and NO2--N, and when NO3--N was its sole nitrogen source, 92.28% of the NO3--N (150 mg·L-1) was converted to NO2--N. However, when NH4+-N and NO3--N constituted the mixed nitrogen source, NO3--N utilization by this strain was significantly lower (p < 0.05). Therefore, a strategy was proposed to combine pw-6 bacteria with traditional autotrophic nitrification to achieve the application of pw-6 bacteria in NH4+-N-containing wastewater treatment. Bioaugmented application experiments showed significantly higher NH4+-N removal (5.96 ± 0.94 mg·L-1·h-1) and lower NO3--N accumulation (2.52 ± 0.18 mg·L-1·h-1) rates (p < 0.05) than those observed for the control test. Thus, AD bacteria with high NO2--N accumulation can also be used for practical applications, providing a basis for expanding the selection range of AD strains for wastewater treatment.
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Comamonas , Desnitrificación , Nitrógeno , Eliminación de Residuos Líquidos , Aguas Residuales , Nitrógeno/metabolismo , Comamonas/metabolismo , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/química , Aerobiosis , Purificación del Agua/métodos , Contaminantes Químicos del Agua/metabolismoRESUMEN
The tourism network attention as a reflection of tourism demand is closely related to the tourism flow, the differences between the two has become an important criterion for judging the efficiency of destination tourism demand conversion, as well as a manifestation of the balance and coordination of destination tourism industry. Against the background of insufficient release of tourism demand in China, research on the development differences between tourism network attention and tourism flow can provide a basis for demand-side management and high-quality development. Based on the theory of spatial mismatch, this research analyzes the spatial development difference between the tourism network attention and the tourism flow in Shanghai from 2012 to 2021 using methods such as center of gravity model, spatial mismatch index, and two-dimensional combination matrix. The results show: (1) According to the analysis of the center of gravity model, there was a shift of the center of gravity of tourism network attention with the direction of "south-north", while the tourism flow shifted "west-east"; the center of gravity between tourism network attention and tourism flow began to diverge from 2012 to 2016, gradually converged from 2016 to 2019, and then gradually deviated again after 2020. (2) According to the spatial mismatch index, the spatial mismatch types between tourism network attention and tourism flow in various Districts of Shanghai are mainly negative and low mismatch, with high mismatch areas mainly distributed in the eastern and southwestern parts of Shanghai. (3) Combining the two-dimensional combination matrix, it can be observed that the spatial development difference between tourism network attention and tourism flow in Shanghai show a characteristic of "enlarging-shrinking-enlarging". From 2012 to 2016, the spatial development difference between tourism network attention and tourism flow in Shanghai continuously expanded; from 2017 to 2019, the spatial development difference continuously shrank; and from 2020 to 2021, the spatial differences expanded again. (4) The analysis results of the panel data model show that the development of tourism resources and the level of tourism services have a positive promoting effect on the evolution of spatial mismatch, while the social basic development environment has a negative effect. The research results not only meet the needs of evaluating the high-quality development of the tourism industry in the current economic restructuring, providing direction for the high-quality development of the regional tourism industry, but also enrich the research content of network attention as a tourism element participating in the evaluation of tourism industry development quality, and deepen the relationship research between network attention and tourism flow.
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PURPOSE: This study aimed to describe the clinical features, diagnostic and therapeutic course of a patient with MODY13 caused by KCNJ11 (c.101G > A, p.R34H) and how it contributes to the pathogenesis of MODY13, and to explore new therapeutic targets. METHODS: Whole-exome sequencing was used to screen prediagnosed individuals and family members with clinically suspected KCNJ11 mutations. Real-time fluorescence quantitative PCR, western blotting, thallium flux of potassium channels, glucose-stimulated insulin secretion (GSIS), and immunofluorescence assays were used to analyze the regulation of insulin secretion by the KCNJ11 mutant in MIN6 cells. Daily blood glucose levels were continuously monitored for 14 days in the proband using the ambulatory blood glucose meter (SIBIONICS). RESULTS: Mutation screening of the entire exon of the gene identified a heterozygous KCNJ11 (c.101G > A, p.R34H) mutation in the proband and his mother. Cell-based GSIS assays after transfection of MIN6 using wild-type and mutant plasmids revealed that this mutation impaired insulin secretory function. Furthermore, we found that this impaired secretory function is associated with reduced functional activity of the mutant KCNJ11 protein and reduced expression of the insulin secretion-associated exocytosis proteins STXBP1 and SNAP25. CONCLUSION: For the first time, we revealed the pathogenic mechanism of KCNJ11 (c.101G > A, p.R34H) associated with MODY13. This mutant can cause alterations in KATP channel activity, reduce sensitivity to glucose stimulation, and impair pancreatic ß-cell secretory function by downregulating insulin secretion-associated exocytosis proteins. Therefore, oral sulfonylurea drugs can lower blood glucose levels through pro-insulinotropic effects and are more favorable for patients with this mutation.
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BACKGROUND: The cognitive impairment in type 2 diabetes mellitus (T2DM) is a multifaceted and advancing state that requires further exploration to fully comprehend. Neuroinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease. AIM: To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment. METHODS: To identify differentially expressed genes (DEGs) between T2DM and controls, we used data from the Gene Expression Omnibus database GSE125387. To identify T2DM module genes, we used Weighted Gene Co-Expression Network Analysis. All the genes were subject to Gene Set Enrichment Analysis. Protein-protein interaction network construction and machine learning were utilized to identify three hub genes. Immune cell infiltration analysis was performed. The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis. Validation experiments including reverse transcription quantitative real-time PCR, Western blotting and immunohistochemistry were conducted both in vivo and in vitro. To identify potential drugs associated with hub genes, we used the Comparative Toxicogenomics Database (CTD). RESULTS: A total of 576 DEGs were identified using GSE125387. By taking the intersection of DEGs, T2DM module genes, and immune-related genes, a total of 59 genes associated with the immune system were identified. Afterward, machine learning was utilized to identify three hub genes (H2-T24, Rac3, and Tfrc). The hub genes were associated with a variety of immune cells. The three hub genes were validated in GSE152539. Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro, consistent with the bioinformatics analysis. Additionally, 11 potential drugs associated with RAC3 and TFRC were identified based on the CTD. CONCLUSION: Immune-related genes that differ in expression in the hippocampus are closely linked to microglia. We validated the expression of three hub genes both in vivo and in vitro, consistent with our bioinformatics results. We discovered 11 compounds associated with RAC3 and TFRC. These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.
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OBJECTIVE: To investigate the correlation between serum ferritin (SF) and bone turnover markers in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Seven hundred and forty-two people with T2DM were selected. Serum bone turnover markers: osteocalcin (OC), type I procollagen N-terminal peptide (PINP), ß-I type collagen carboxy-terminal peptide (ß-CTx), and 25-hydroxyvitamin D3 (25-[OH]-D) levels were detected. High SF (HF) was defined as the indicated SF levels above 400 ng/mL in males and more than 150 ng/mL in females. Patients were divided into four groups: T2DM+normal SF (non-HF); T2DM+high SF (HF); T2DM+NAFLD+non-HF; andT2DM+NAFLD+HF. Relationships between SF and bone turnover markers were analyzed. RESULTS: Compared with the T2DM+non-HF group, ß-CTx levels were higher in the T2DM+HFgroup. Compared with the T2DM+NAFLD+non-HF group, ß-CTx levels were increased and 25-(OH)-D levels decreased in the T2DM+NAFLD+HF group (all p < 0.05). SF was positively correlated with ß-CTx [ß = 0.074; 95% CI (0.003, 0.205)] and negatively correlated with 25-(OH)-D [ß=-0.108; 95%CI (-0.006, -0.001)]. Compared with the T2DM+non-HF group, an independent positive correlation was found between ß-CTx and SF in the T2DM+NAFLD+HF group [OR = 1.002; 95% CI (1.001, 1.004)]. Among males, SF was positively correlatedwith ß-CTx [ß = 0.114; 95% CI (0.031, 0.266)]. SF was negatively correlated with 25-(OH)-D levels in both male and female patients [ß=-0.124; 95% CI (0.007,0.001) and ß=-0.168; 95% CI (-0.012, -0.002)]. Among those >50 years of age and postmenopausal females, SF was negatively correlated with 25-(OH)-D levels [ß=-0.117; 95% CI (-0.007, -0.001) and ß=-0.003; 95% CI (-0.013, -0.003)]. CONCLUSION: SF level was positively correlated with ß-CTx in T2DM patients with NAFLD, which may promote bone resorption and increase the risk of bone loss.
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Biomarcadores , Remodelación Ósea , Diabetes Mellitus Tipo 2 , Ferritinas , Enfermedad del Hígado Graso no Alcohólico , Osteocalcina , Procolágeno , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Femenino , Enfermedad del Hígado Graso no Alcohólico/sangre , Persona de Mediana Edad , Ferritinas/sangre , Biomarcadores/sangre , Osteocalcina/sangre , Procolágeno/sangre , Anciano , Fragmentos de Péptidos/sangre , Calcifediol/sangre , Colágeno Tipo I/sangre , Adulto , PéptidosRESUMEN
BACKGROUND: The shoulder joint is the most commonly dislocated joint in the human body, and the recurrence rate exceeds 50% after nonsurgical treatment. Although surgical treatment reduces the recurrence rate, there is controversy regarding the optimal surgical approach. Previous studies suggest that the Latarjet procedure yields favourable outcomes for specific populations at risk of recurrence, such as competitive athletes with significant glenoid defects. However, most of the existing related research consists of nonrandomized controlled trials with small sample sizes, and there is a lack of strong evidence regarding the efficacy and safety of the Latarjet procedure. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched. Athletes with ≥ 20% glenoid defects were selected for inclusion. The following data were extracted: general patient information, instability rates, return to sports (RTS) rates, imaging features (graft positioning rate and graft healing rate), functional assessments [Rowe score, Athletic Shoulder Outcome Scoring System(ASOSS), visual analogue scale (VAS), forward flexion function, and external rotation function], and complications. RESULTS: After excluding suspected duplicate cases, a total of 5 studies were included in this meta-analysis. The studies involved a total of 255 patients, including 237 males (93%) and 18 females (7%). The average age at the time of surgery was 25.4 ± 8.5 years. All the studies had a minimum follow-up period of 2 years, with an average follow-up time of 48.7 ± 18.9 months. The pooled rate of return to sport (RTS) was 94.3% (95% CI: 87.3%, 98.8%), and 86.1% (95% CI: 78.2%, 92.5%) of patients returned to their preoperative level of activity. The pooled redislocation rate was 1.1% (95% CI: 0%, 3.8%). Regarding the imaging results, the combined graft retention rate was 92.1% (95% CI: 88.1%, 95.5%), and the graft healing rate was 92.1% (95% CI: 88%, 95.4%). Postoperative functional evaluation revealed that the combined Rowe score, ASOSS score, and VAS score were 93.7 ± 6.5 points, 88.5 ± 4.4 points, and 1.1 ± 10 points, respectively. The forward flexion and external rotation angles were 170.9 ± 6.9 degrees and 65.6 ± 4.5 degrees, respectively. After excluding one study with unclear complications, the combined complication rate was 9.4% (95% CI: 1.0%, 23.6%). CONCLUSION: For athletes with shoulder instability and a total of ≥ 20% glenoid bone defects, the Latarjet procedure can achieve excellent functional outcomes, with the majority of patients returning to preoperative levels of sports activity. This procedure also leads to a low recurrence rate. Therefore, the Latarjet procedure has been proven to be a safe and effective treatment.
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Inestabilidad de la Articulación , Luxación del Hombro , Articulación del Hombro , Masculino , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/cirugía , Luxación del Hombro/diagnóstico por imagen , Luxación del Hombro/cirugía , Inestabilidad de la Articulación/cirugía , Escápula/cirugía , AtletasRESUMEN
Aim: To explore the effects of Tirzepatide (TZP), a new hypoglycemic drug, on weight, blood lipids and blood pressure in overweight/obese patients with type 2 diabetes mellitus (T2DM). Methods: Relevant studies investigating the influence of TZP therapy on weight, lipid profiles and blood pressure in overweight/obese T2DM patients were selected from the PubMed, Embase, Web of Science and Cochrane databases from establishment until November 2022. A systematic review and meta-analysis were conducted to evaluate the effect of TZP on weight, blood lipids and blood pressure in overweight/obese patients with T2DM. Results: Eight randomized controlled trials (RCTs), comprising 7491 patients with T2DM, were included in the meta-analysis. Results showed that compared with the glucagon-like peptide-1 receptor agonist (GLP-1RA), insulin, and placebo groups, body weight, triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) levels were significantly decreased in the TZP-treated groups, while high-density lipoprotein cholesterol (HDL-C) levels increased. With the gradual increase of TZP doses, the proportions of T2DM patients with weight loss >5% gradually increased. The 10 mg and 15 mg TZP doses had a stronger effect on the levels of TG, VLDL-C, and HDL-C. Moreover, the reduction in SBP levels in the 15 mg TZP-treated group was more pronounced than those in the 10 mg and 5 mg TZP-treated groups [MD=-2.07, 95% CI (-2.52, -1.63) and MD=-3.14, 95% CI (-4.42, -1.87)]. Compared with GLP-1RA, insulin, and placebo groups, the proportions of patients with HbA1c<7% in 10mg and 15mg TZP-treated groups were significantly higher than in the 5mg TZP-treated group [OR=1.53, 95% CI (1.25, 1.8)], OR=1.7, 95% CI (1.15, 2.50)].There was no significant difference regarding the risk of adverse reactions.
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PURPOSE: Prolonged exposure to plasma free fatty acids (FFAs) leads to impaired glucose tolerance (IGT) which can progress to type 2 diabetes (T2D) in the absence of timely and effective interventions. High-fat diet (HFD) leads to chronic inflammation and oxidative stress, impairing pancreatic beta cell (PBC) function. While Didymin, a flavonoid glycoside derived from citrus fruits, has beneficial effects on inflammation dysfunction, its specific role in HFD-induced IGT remains yet to be elucidated. Hence, this study aims to investigate the protective effects of Didymin on PBCs. METHODS: HFD-induced IGT mice and INS-1 cells were used to explore the effect and mechanism of Didymin in alleviating IGT. Serum glucose and insulin levels were measured during the glucose tolerance and insulin tolerance tests to evaluate PBC function and insulin resistance. Next, RNA-seq analysis was performed to identify the pathways potentially influenced by Didymin in PBCs. Furthermore, we validated the effects of Didymin both in vitro and in vivo. Mitochondrial electron transport inhibitor (Rotenone) was used to further confirm that Didymin exerts its ameliorative effect by enhancing mitochondria function. RESULTS: Didymin reduces postprandial glycemia and enhances 30-minute postprandial insulin levels in IGT mice. Moreover, Didymin was found to enhance mitochondria biogenesis and function, regulate insulin secretion, and alleviate inflammation and apoptosis. However, these effects were abrogated with the treatment of Rotenone, indicating that Didymin exerts its ameliorative effect by enhancing mitochondria function. CONCLUSIONS: Didymin exhibits therapeutic potential in the treatment of HFD-induced IGT. This beneficial effect is attributed to the amelioration of PBC dysfunction through improved mitochondrial function.
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Most red-fleshed kiwifruit cultivars, such as Hongyang, only accumulate anthocyanins in the inner pericarp; the trait of full red flesh becomes the goal pursued by breeders. In this study, we identified a mutant "H-16" showing a red color in both the inner and outer pericarps, and the underlying mechanism was explored. Through transcriptome analysis, a key differentially expressed gene AcGST1 was screened out, which was positively correlated with anthocyanin accumulation in the outer pericarp. The result of McrBC-PCR and bisulfite sequencing revealed that the SG3 region (-292 to -597 bp) of AcGST1 promoter in "H-16" had a significantly lower CHH cytosine methylation level than that in Hongyang, accompanied by low expression of methyltransferase genes (MET1 and CMT2) and high expression of demethylase genes (ROS1 and DML1). Transient calli transformation confirmed that demethylase gene DML1 can activate transcription of AcGST1 to enhance its expression. Overexpression of AcGST1 enhanced the anthocyanin accumulation in the fruit flesh and leaves of the transgenic lines. These results suggested that a decrease in the methylation level of the AcGST1 promoter may contribute to accumulation of anthocyanin in the outer pericarp of "H-16".
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Actinidia , Frutas , Frutas/química , Antocianinas/metabolismo , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/genética , Metilación de ADN , Actinidia/genética , Actinidia/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a medicinal herb for liver diseases. Didymin is a newly identified oral bioactive dietary flavonoid glycoside derived from Chenpi. In this study, we investigated the therapeutic potential of Didymin as an anti-MAFLD drug and elucidated its underlying mechanisms. METHODS: High-fat diet (HFD)-induced MAFLD mice and alpha mouse liver 12 (AML12) cells were utilized to evaluate the effects and mechanisms of Didymin in the treatment of MAFLD. Liver weight, serum biochemical parameters, and liver morphology were examined to demonstrate the therapeutic efficacy of Didymin in MAFLD treatment. RNA-seq analysis was performed to identify potential pathways that could be affected by Didymin. The impact of Didymin on Sirt1 was corroborated through western blot, molecular docking analysis, microscale thermophoresis (MST), and deacetylase activity assay. Then, a Sirt1 inhibitor (EX-527) was utilized to confirm that Didymin alleviates MAFLD via Sirt1. Western blot and additional assays were used to investigate the underlying mechanisms. RESULTS: Our results suggested that Didymin may possess therapeutic potential against MAFLD in vitro and in vivo. By promoting Sirt1 expression as well as directly binding to and activating Sirt1, Didymin triggers downstream pathways that enhance mitochondrial biogenesis and function while reducing apoptosis and enhancing lipophagy. CONCLUSIONS: These suggest that Didymin could be a promising medication for MAFLD treatment. Furthermore, its therapeutic effects are mediated by Sirt1.
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Enfermedad del Hígado Graso no Alcohólico , Sirtuina 1 , Animales , Ratones , Sirtuina 1/metabolismo , Biogénesis de Organelos , Simulación del Acoplamiento Molecular , Flavonoides/farmacología , Flavonoides/uso terapéutico , Glicósidos/farmacología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Hígado/metabolismoRESUMEN
Fast and effective hemostasis and protection against wound infection play a crucial role in trauma care. In this study, a sponge scaffold with a self-expanding interpenetrating macropore structure was designed via two-step cross-linking method for hemostasis and photothermal antimicrobial activity. Oxidized Konjac glucomannan (OKGM) and chitosan (CS) were crosslinked once to form a dynamic covalent bonding network, and a basic three-dimensional fiber porous network framework was constructed by uniformly dispersing Tunicate nanocellulose (TCNCs). Secondary crosslinking introduced Polydopamine (PDA NPs) into the sponge, while dynamic hydrogen bonds were interleaved to stabilize the frame. PDA NPs enhanced the sponge's antibacterial and antioxidant properties due to its good photothermal conversion efficiency and oxygen radical scavenging ability. Compared to cotton gauze and gelatin sponges, the composite sponges showed superior blood cell adhesion and platelet activation. In tests on rat liver trauma models, composite sponges showed shorter hemostasis time (12 ± 2.17 s) and less blood loss (0.1 ± 0.052 g). Sponges can protect wound tissue through their adhesion properties. In the full-thickness wound model infected with S. aureus, the composite sponge accelerated wound healing. Overall, this composite sponge has great potential for clinical use as a wound dressing.
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Fabricating a cost-effective yet highly active photocatalyst to reduce CO2 to CO and oxidize benzyl alcohol to benzaldehyde simultaneously, is challenging. Herein, we construct an S-scheme 0D/2D CsPbBr3/TiO2 heterostructure for bifunctional photocatalysis. An in-situ synthetic route is used, which enables the precise integration between CsPbBr3 nanocrystals and ultrathin TiO2 nanosheets exposed with (001) facets (termed as TiO2-001), resulting in a tightly coupled heterointerface and desirable band offsets. The as-prepared CsPbBr3/TiO2-001heterojunctions exhibit boosted charge carrier kinetics, particularly, quick carrier separation/transfer and efficient utilization. Experimental results and theoretical calculations validate the S-scheme route in CsPbBr3/TiO2-001, which allows the enrichment of strongly conserved electrons-holes at conduction and valence bands of CsPbBr3 and TiO2-001, respectively. Consequently, compared to its counterparts, an excellent bifunctional activity (with 24 h reusability) is realized over CsPbBr3/TiO2-001, where the production rate of CO and benzaldehyde reach up to 78.06 µmol g-1h-1 and 1.77 mmol g-1h-1 respectively, without employing any sacrificial agents. This work highlights the development of perovskite-based heterostructures and describes the efficient harnessing of redox potentials and charge carriers towards combined photocatalytic systems.
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AIMS: BACH1 is up-regulated in hypertrophic hearts, but its function in cardiac hypertrophy remains largely unknown. This research investigates the function and mechanisms of BACH1 in the regulation of cardiac hypertrophy. METHODS AND RESULTS: Male cardiac-specific BACH1 knockout mice or cardiac-specific BACH1 transgenic (BACH1-Tg) mice and their respective wild-type littermates developed cardiac hypertrophy induced by angiotensin II (Ang II) or transverse aortic constriction (TAC). Cardiac-specific BACH1 knockout in mice protected the hearts against Ang II- and TAC-induced cardiac hypertrophy and fibrosis, and preserved cardiac function. Conversely, cardiac-specific BACH1 overexpression markedly exaggerated cardiac hypertrophy and fibrosis and reduced cardiac function in mice with Ang II- and TAC-induced hypertrophy. Mechanistically, BACH1 silencing attenuated Ang II- and norepinephrine-stimulated calcium/calmodulin-dependent protein kinase II (CaMKII) signalling, the expression of hypertrophic genes, and hypertrophic growth of cardiomyocytes. Ang II stimulation promoted the nuclear localization of BACH1, facilitated the recruitment of BACH1 to the Ang II type 1 receptor (AT1R) gene promoter, and then increased the expression of AT1R. Inhibition of BACH1 attenuated Ang II-stimulated AT1R expression, cytosolic Ca2+ levels, and CaMKII activation in cardiomyocytes, whereas overexpression of BACH1 led to the opposite effects. The increased expression of hypertrophic genes induced by BACH1 overexpression upon Ang II stimulation was suppressed by CaMKII inhibitor KN93. The AT1R antagonist, losartan, significantly attenuated BACH1-mediated CaMKII activation and cardiomyocyte hypertrophy under Ang II stimulation in vitro. Similarly, Ang II-induced myocardial pathological hypertrophy, cardiac fibrosis, and dysfunction in BACH1-Tg mice were blunted by treatment with losartan. CONCLUSION: This study elucidates a novel important role of BACH1 in pathological cardiac hypertrophy by regulating the AT1R expression and the Ca2+/CaMKII pathway, and highlights potential therapeutic target in pathological cardiac hypertrophy.
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Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Calcio , Ratones , Masculino , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Calcio/metabolismo , Losartán , Cardiomegalia/metabolismo , Miocitos Cardíacos/metabolismo , Ratones Transgénicos , Angiotensina II/metabolismo , Ratones Noqueados , Fibrosis , Ratones Endogámicos C57BLRESUMEN
Diabetic cardiomyopathy (DCM) is a serious complication of type 1 and type 2 diabetes, which leads to the aggravation of myocardial fibrosis, disorders involving systolic and diastolic functions, and increased mortality of patients with diabetes through mechanisms such as glycolipid toxicity, inflammatory response, and oxidative stress. Ferroptosis is a form of iron-dependent regulatory cell death that is attributed to the accumulation of lipid peroxides and an imbalance in redox regulation. Increased production of lipid reactive oxygen species (ROS) during ferroptosis promotes oxidative stress and damages myocardial cells, leading to myocardial systolic and diastolic dysfunction. Overproduction of ROS is an important bridge between ferroptosis and DCM, and ferroptosis inhibitors may provide new targets for the treatment of patients with DCM.
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Diabetes Mellitus Tipo 2 , Cardiomiopatías Diabéticas , Ferroptosis , Humanos , Cardiomiopatías Diabéticas/metabolismo , Ferroptosis/fisiología , Especies Reactivas de Oxígeno/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Miocardio/metabolismoRESUMEN
PURPOSE: To investigate the relationship between the triglyceride-glucose (TyG) index and serum ferritin (SF) levels in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 881 T2DM patients were divided into T1(TyG index < 1.66), T2 (1.66 ≤ TyG index < 2.21), and T3 (TyG index ≥ 2.21) groups according to the tertiles of the TyG index. The differences in SF levels and the prevalence of hyperferritinemia (SF ≥ 300 ng/mL for male or SF ≥ 150 ng/mL for female) were compared. The independent correlations between the TyG index and SF, and between hyperferritinemia and TyG in T2DM patients were analyzed, respectively. RESULTS: SF levels in male T2DM patients were higher in the T3 group (250.12 ng/mL) than in the T1 and T2 groups (180.45 and 196.56 ng/mL, both p < 0.01),while in female patients with T2DM,SF levels were higher in the T3 group (157.25 ng/mL) than in the T1 group (111.06 ng/mL, p < 0.05).The prevalence of hyperferritinemia in male T2DM patients was higher in the T3 group (31.3%) than those in the T1 and T2 groups (10.4% and 17.3%, both p < 0.05).The TyG index was positively correlated with SF levels in T2DM patients (R = 0.178, p < 0.001).TyG index was independently and positively correlated with SF levels after adjusting for confounders (ß = 0.097, 95%CI [2.870,38.148], p = 0.023).The TyG index was positively independently correlated with hyperferritinemia in male T2DM patients (OR = 1.651, 95%CI [1.120,2.432], p = 0.011). CONCLUSIONS: In parallel with increasing TyG index SF levels gradually increased. The TyG index was positively correlated with SF levels in patients with T2DM and was positively correlated with hyperferritinemia in male T2DM patients.
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Diabetes Mellitus Tipo 2 , Hiperferritinemia , Humanos , Masculino , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Glucosa , Factores de Riesgo , Glucemia , TriglicéridosRESUMEN
In neuroimaging research, univariate analysis has always been used to localize "representations" at the microscale, whereas network approaches have been applied to characterize transregional "operations". How are representations and operations linked through dynamic interactions? We developed the variational relevance evaluation (VRE) method to analyze individual task fMRI data, which selects informative voxels during model training to localize the "representation", and quantifies the dynamic contributions of single voxels across the whole-brain to different cognitive functions to characterize the "operation". Using 15 individual fMRI data files for higher visual area localizers, we evaluated the characterization of selected voxel positions of VRE and revealed different object-selective regions functioning in similar dynamics. Using another 15 individual fMRI data files for memory retrieval after offline learning, we found similar task-related regions working in different neural dynamics for tasks with diverse familiarities. VRE demonstrates a promising horizon in individual fMRI research.