ABSTRACT
BACKGROUND: The effect of tumor budding (TB) on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after endoscopic submucosal dissection (ESD) remains unclear. We evaluated the long-term outcomes of patients with superficial ESCC after ESD and the risk factors of TB for the long-term prognosis. METHODS: We conducted a retrospective study in a Chinese hospital. All patients with ESCC treated by ESD and reported TB were included consecutively. Comparative analyses were conducted in three parts: specimen analysis, follow-up analyses of unmatched patients, and propensity score-matched (PSM) patients. Cox proportional hazard regression models were constructed to identify risk factors for overall survival and recurrence-free survival (RFS). RESULTS: A total of 437 patients were enrolled [154 TB and 283 no tumor budding (NTB)], and 258 patients (52 TB and 206 NTB) were included in the follow-up analysis. Results showed that the invasion depth, differentiation type, and positive vascular invasion (all p < 0.001) of the TB group were significantly different from the NTB group. The all-cause mortality and the median RFS time between the two groups were comparable. RFS rate at 5 years were 84.6% and 80.6%, respectively (p = 0.43). Cox analyses identified that having other cancers but not TB, as a risk factor independently associated with overall survival and RFS after ESD. CONCLUSION: TB tends to be associated with invasion depth, differentiation type, and positive vascular invasion. However, it might not affect the long-term outcomes of patients with superficial ESCC after ESD when other high-risk factors are negative.
ABSTRACT
Skin provides a physical and immune barrier to protect the body from foreign substances, microbial invasion, and desiccation. Aging reduces the barrier function of skin and its rate of repair. Aged skin exhibits decreased mitochondrial function and prolonged low-level inflammation that can be seen in other organs with aging. Peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), an important transcriptional coactivator, plays a central role in modulating mitochondrial function and antioxidant production. Mitochondrial function and inflammation have been linked to epidermal function, but the mechanisms are unclear. The aim of this review is to discuss the mechanisms by which PGC-1α might exert a positive effect on aged skin barrier function. Initially, we provide an overview of the function of skin under physiological and aging conditions, focusing on the epidermis. We then discuss mitochondrial function, oxidative stress, cellular senescence, and inflamm-aging, the chronic low-level inflammation observed in aging individuals. Finally, we discuss the effects of PGC-1α on mitochondrial function, as well as the regulation and role of PGC-1α in the aging epidermis.
Subject(s)
Mitochondria , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Skin Aging , Humans , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Skin Aging/physiology , Mitochondria/metabolism , Animals , Skin/metabolism , Skin/pathology , Aging/metabolism , Oxidative Stress , Inflammation/metabolism , Inflammation/pathology , Cellular SenescenceABSTRACT
Frequency-dependent predation is common in predator-prey interactions. Size is an important characteristic of seeds and is crucial in the regeneration stage of plant seeds. However, the frequency dependence of animal predation on seed size has not been reported. In this study, we conducted a field experiment and used different sizes of Liaodong oak (Quercus wutaishanica) seeds to test the frequency dependence of intraspecific seed size selection in rodents. We used the number ratio of large to small seeds as the frequency. The results show that the rate of small seeds being eaten in situ was significantly higher than that of large seeds (p < 0.05). The rates of different-sized seeds being eaten after removal decreased with increasing frequencies, and there was no significant difference between frequencies except for 1:9 and 9:1. The rates of large seeds being scatter-hoarded were significantly higher than those of small seeds at different frequencies (p < 0.05). The eating distances after removal of large seeds were significantly longer than those of small seeds at the same frequencies (p < 0.05). Furthermore, the scatter-hoarding distances of large seeds were significantly longer than those of small seeds at three frequencies (1:9, 3:7, and 9:1) (p < 0.05). That is, rodents consumed more small seeds in situ, dispersed and scatter-hoarded more large seeds, and dispersed large seeds over longer distances. Rodents exhibited a negative frequency dependence for small seeds and a positive frequency dependence for large seeds on being eaten in situ. Moreover, rodents exhibited a negative frequency dependence for large seeds and a positive frequency dependence for small seeds on being eaten after removal and scatter-hoarding. These results reveal the frequency dependence of rodent selection on seed size and provide new insights into animal-mediated seed dispersal and the regeneration of plant populations.
ABSTRACT
The increases in extent and frequency of extreme drought events and increased nitrogen (N) deposition due to global change are expected to have profound impacts on carbon cycling in semi-arid grasslands. However, how ecosystem CO2 exchange processes respond to different drought scenarios individually and interactively with N addition remains uncertain. In this study, we experimentally explored the effects of different drought scenarios (early season extreme drought, 50 % reduction in precipitation amount, and 50 % reduction in precipitation events) and N addition on net ecosystem CO2 exchange (NEE), ecosystem respiration (ER), and gross ecosystem productivity (GEP) over three growing seasons (2019-2021) in a semi-arid grassland in northern China. The growing-season ecosystem carbon fluxes in response to drought and N addition were influenced by inter-annual precipitation changes, with 2019 as a normal precipitation year, and 2020 and 2021 as wet years. Early season extreme drought stimulated NEE by reducing ER. 50 % reduction in precipitation amount decreased ER and GEP consistently in three years, but only significantly suppressed NEE in 2019. 50 % reduction in precipitation events stimulated NEE. Nitrogen addition stimulated NEE, ER, and GEP, but only significantly in wet years. The structural equation models showed that changes in carbon fluxes were regulated by soil moisture, soil temperature, microbial biomass nitrogen (MBN), and the key plant functional traits. Decreased community-weighted means of specific leaf area (CWMSLA) was closely related to the reduced ER and GEP under early season extreme drought and 50 % reduction in precipitation amount. While increased community-weighted means of plant height (CWMPH) largely accounted for the stimulated ER and GEP under 50 % reduction in precipitation events. Our study stresses the distinct effects of different drought scenarios and N enrichment on carbon fluxes, and highlights the importance of soil traits and the key plant traits in determining carbon exchange in this water-limited ecosystem.
Subject(s)
Carbon Cycle , Droughts , Grassland , Nitrogen , Nitrogen/analysis , China , Rain , Climate Change , Ecosystem , Carbon/metabolism , SeasonsABSTRACT
Drought and nitrogen enrichment could profoundly affect the productivity of semiarid ecosystems. However, how ecosystem productivity will respond to different drought scenarios, especially with a concurrent increase in nitrogen availability, is still poorly understood. Using data from a 4-year field experiment conducted in a semiarid temperate steppe, we explored the responses of aboveground net primary productivity (ANPP) to different drought scenarios and nitrogen addition, and the underlying mechanisms linking soil properties, plant species richness, functional diversity (community-weighted means of plant traits, functional dispersion) and phylogenetic diversity (net relatedness index) to ANPP. Our results showed that completely excluding precipitation in June (1-month intense drought) and reducing half the precipitation amount from June to August (season-long chronic drought) both significantly reduced ANPP, with the latter having a more negative impact on ANPP. However, reducing half of the precipitation frequency from June to August (precipitation redistribution) had no significant effect on ANPP. Nitrogen addition increased ANPP irrespective of drought scenarios. ANPP was primarily determined by soil moisture and nitrogen availability by regulating the community-weighted means of plant height, rather than other aspects of plant diversity. Our findings suggest that precipitation amount is more important than precipitation redistribution in influencing the productivity of temperate steppe, and nitrogen supply could alleviate the adverse impacts of drought on grassland productivity. Our study advances the mechanistic understanding of how the temperate grassland responds to drought stress, and implies that management strategies to protect tall species in the community would be beneficial for maintaining the productivity and carbon sequestration of grassland ecosystems under climate drought.
Subject(s)
Droughts , Grassland , Nitrogen , Nitrogen/metabolism , Plants/classification , Soil/chemistry , ChinaSubject(s)
Drainage , Stents , Humans , Male , Female , Middle Aged , Drainage/methods , Adult , Aged , Gallstones/surgeryABSTRACT
Background: Recent studies have revealed a significant decrease in serum fetuin-A levels in atherosclerotic aneurysms, indicating that fetuin-A may play a protective role in the progression of arterial calcification. However, the specific mechanism behind this phenomenon remains unclear. We aimed to examine the association between fetuin-A levels in thoracic aortic aneurysms (TAAs) and risk of TAAs and to evaluate whether this association was causal. Methods: A total of 26 SNPs were selected as instrumental variables for fetuin-A in 9,055 participants of European ancestry from the CHARGE consortium, and their effects on thoracic aortic aneurysm and decreased descending thoracic aortic diameter were separately estimated in 353,049 and 39,688 individuals from FinnGen consortium. We used two-sample Mendelian randomization (MR) analysis to examine the causal association. At the same time, we employed various methods, including random-effects inverse variance weighting, weighted median, MR Egger regression, and MR PRESSO, to ensure the robustness of causal effects. We assessed heterogeneity using Cochran's Q value and examined horizontal pleiotropy through MR Egger regression and retention analysis. Results: Fetuin-A level was associated with a significantly decreasing risk of thoracic aortic aneurysm (odds ratio (OR) 0.64, 95% CI 0.47 - 0.87, P = 0.0044). Genetically predicted fetuin-A was also correlated with the decreased descending thoracic aortic diameter (ß = -0.086, standard error (SE) 0.036, P = 0.017). Conclusions: Serum fetuin-A level was negatively associated with risk of TTAs and correlated with the decreased descending thoracic aortic diameter. Mendelian randomization provides support for the potential causal relationship between fetuin-A and thoracic aortic aneurysm.
Subject(s)
Aortic Aneurysm, Thoracic , alpha-2-HS-Glycoprotein , Humans , alpha-2-HS-Glycoprotein/genetics , Mendelian Randomization Analysis , Aortic Aneurysm, Thoracic/genetics , Odds Ratio , Polymorphism, Single NucleotideABSTRACT
Background: Substantial evidence suggests an association between psychiatric disorders and chronic heart failure. However, further investigation is needed to confirm the causal relationship between these psychiatric disorders and chronic heart failure. To address this, we evaluated the potential effects of five psychiatric disorders on chronic heart failure using two-sample Mendelian Randomization (MR). Methods: We selected single nucleotide polymorphisms (SNPs) associated with chronic heart failure and five psychiatric disorders (Attention-Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Major Depression, Bipolar Disorder and Schizophrenia (SCZ)). Univariable (UVMR) and multivariable two-sample Mendelian Randomization (MVMR) were employed to assess causality between these conditions. Ever smoked and alcohol consumption were controlled for mediating effects in the multivariable MR. The inverse variance weighting (IVW) and Wald ratio estimator methods served as the primary analytical methods for estimating potential causal effects. MR-Egger and weighted median analyses were also conducted to validate the results. Sensitivity analyses included the funnel plot, leave-one-out, and MR-Egger intercept tests. Additionally, potential mediators were investigated through risk factor analyses. Results: Genetically predicted heart failure was significantly associated with ADHD (odds ratio (OR), 1.12; 95% CI, 1.04-1.20; p = 0.001), ASD (OR, 1.29; 95% CI, 1.07-1.56; p = 0.008), bipolar disorder (OR, 0.89; 95% CI, 0.83-0.96; p = 0.001), major depression (OR, 1.15; 95% CI, 1.03-1.29; p = 0.015), SCZ (OR, 1.04; 95% CI, 1.00-1.07; p = 0.024). Several risk factors for heart failure are implicated in the above cause-and-effect relationship, including ever smoked and alcohol consumption. Conclusion: Our study demonstrated ADHD, ASD, SCZ and major depression may have a causal relationship with an increased risk of heart failure. In contrast, bipolar disorder was associated with a reduced risk of heart failure, which could potentially be mediated by ever smoked and alcohol consumption. Therefore, prevention strategies for heart failure should also incorporate mental health considerations, and vice versa.
Subject(s)
Autism Spectrum Disorder , Heart Failure , Mental Disorders , Humans , Mendelian Randomization Analysis , Mental Disorders/epidemiology , Mental Disorders/genetics , Mental Health , Chronic Disease , Heart Failure/epidemiology , Heart Failure/geneticsABSTRACT
BACKGROUND: Circular RNA is a type of non-coding RNA that is commonly found in eukaryotic genomes. They play an essential role in the biological processes of cell proliferation and cell apoptosis involved in normal development and abnormal tumorigenesis. In this study, we examined whether that the circular RNA GENE hsa_circ_0120175 is substantially expressed in epithelial ovarian cancer, and then explored whether hsa_circ_0120175 plays an important role in the occurrence and development of ovarian cancer. METHODS: A total of 40 patients with ovarian cancer were included in this study, and tissue samples were collected from both ovarian cancer tissues and paracancer tissues. The levels of hsa_circ_0120175 expression were determined using qRT-PCR in both varian cancer cells and tissues. This study assessed the impact of hsa_circ_0120175 on cellular proliferation, migration, and invasion using various in vitro assays with cultured ovarian carcinoma cells. RESULTS: Hsa_circ_0120175 was highly expressed in both human tissues and ovarian cancer cells. In ovarian cancer patients, the expression level of hsa_circ_0120175 was significantly different among The International Federation of Gynecology and Obstetrics (FIGO) stages (p = 0.03), and the difference was statistically significant. Multivariate Cox regression analysis showed that lymph node metastasis was independently related to Overall Survival (OS), and the difference was statistically significant (p = 0.033). In vitro, decreasing hsa_circ_0120175 significantly reduced ovarian carcinoma cell proliferation, migration, and invasion (p < 0.05). CONCLUSIONS: Hsa_circ_0120175 has the potential to serve as a biomarker for diagnosing and treating ovarian carcinoma. This is because it promotes cellular proliferation, migration, and invasion in epithelial ovarian carcinoma.
Subject(s)
MicroRNAs , Ovarian Neoplasms , Humans , Female , RNA, Circular/genetics , RNA, Circular/metabolism , Ovarian Neoplasms/genetics , Carcinogenesis/genetics , Cell Transformation, Neoplastic/genetics , Prognosis , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Cell Line, Tumor , Cell Movement/geneticsABSTRACT
Epithelial ovarian cancer (EOC) ranks third in the incidence of gynecological malignancies. m6A methylation as RNA modification plays a crucial role in the evolution, migration, and invasion of various tumors. However, the role of m6A methylation in ovarian cancer (OC) only recently has begun to be appreciated. Therefore, we used various bioinformatic methods to screen the public GEO datasets of epithelial ovarian cancer (EOC) for m6A methylation-related regulators. We identified methyltransferase 16 (METTL16) that was dramatically downregulated in EOC as such a regulator. We also identified metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a known target lncRNA of METTL16, in these five GEO datasets. RT-qPCR and immunohistochemical staining confirmed that compared with the normal ovarian tissues and cells, METTL16 was significantly downregulated, while lncRNA MALAT1 was significantly upregulated, in 30 EOC tissues of our own validation cohorts and EOC cell lines, revealing a negative correlation between METTL16 and lncRNA MALAT1. Moreover, our analysis unveiled a correlation between downregulated METTL16 and the known adverse prognostic factors of EOC patients in our own cohorts. The CCK-8, EdU, scratch wound healing, and transwell invasion assays revealed that METTL16 significantly suppressed the proliferating, migrating, and invading abilities of OC cells. The inhibitory effects of METTL16 on the in vivo tumor growth of EOC cells were measured by subcutaneous tumor formation assay in mice. Furthermore, the RIP, RNA stability assay, western blotting, and cytoimmunofluorescence staining showed that METTL16 hindered the growth of EOC cells through promoting the degradation of MALAT1 by binding that, in turn, upregulates ß-catenin protein and promotes nuclear transport of ß-catenin protein in EOC cells. This study suggests that METTL16 acts as a tumor suppressor gene of EOC by achieving its inhibitory function on the malignant progression of EOC through the METTL16/MALAT1/ß-catenin axis that are new targets for EOC diagnosis and therapy.
Subject(s)
Ovarian Neoplasms , RNA, Long Noncoding , Humans , Animals , Mice , Female , Carcinoma, Ovarian Epithelial/genetics , beta Catenin/genetics , Methyltransferases/genetics , RNA, Long Noncoding/genetics , Ovarian Neoplasms/genetics , Catenins , Cell Line, Tumor , Cell Proliferation/geneticsABSTRACT
The predation and/or dispersal of Quercus seeds by rodents play an important role in the creation of the tree species. The present study examined the effects of community habitats on the predation and dispersal of Quercus wutaishanica seeds by rodents. We released seeds with densities set at 2, 4, 8, 16, and 32 seed square meter with litter cover, soil burial, and bare ground in the Liupan Mountains National Nature Reserve in the Ningxia Hui Autonomous Region, northwest China. The results showed that (1) the litter cover and soil burial significantly increased the seed survival probability compared with bare ground treatments, especially the predation in situ (PIS) (p < 0.05). Both the scatter hoarding (SH) and larder hoarding (LH) for litter cover and soil burial were significantly increased compared with bare ground (p < 0.05). (2) The large seeds are preferentially predated after dispersal and their long-distance dispersal (>5 m) was significantly greater than that of small seeds (p < 0.05), while small seeds are more likely to be preyed on in situ or during short-distance dispersal (<3 m). (3) The Q. wutaishanica seed predation by rodents increased at a high density rather than at a low density, indicating a negative density-dependent predation. These findings provide insights into the ecological characteristics of Quercus tree regeneration and shed light on the coexistence between rodents and different-sized seeds.
ABSTRACT
2D transition metal carbides and nitrides (MXenes) are actively pursued as pseudocapacitive materials for supercapacitors owing to their advantages in electronic conductivity and surface reactivity. Increasing the fraction of âO terminal groups in Ti3 C2 Tx is a promising approach to improve the pseudocapacitive charge storage in H2 SO4 electrolytes, but it suffers from a lack of effective functionalization methods and stability of the groups in practical operation. Here a low-temperature and environment-friendly approach via the interaction of nonequilibrium plasmas with Ti3 C2 Tx dispersion is demonstrated to generate abundant and stable surface-terminating O groups. The impact of the discharge environment (Ar, O2 , and H2 ) on the structural characteristics and electrochemical performance of Ti3 C2 Tx nanosheets is studied. The Ti3 C2 Tx modified in Ar and H2 maintains their original morphology but a significantly lower F content. Consequently, an extraordinarily high content (78.5%) of surface-terminating O groups is revealed by the high-resolution X-ray photoelectron spectroscopy spectra for the Ti3 C2 Tx samples modified in H2 plasma-treated solutions. Additionally, the Ti3 C2 Tx treated using H2 plasmas exhibits the best capacitive performance of 418.3 F g-1 at 2 mV s-1 , which can maintain 95.88% capacity after 10 000 cycles. These results contribute to the development of advanced nanostructured pseudocapacitive electrode materials for renewable energy storage applications.
ABSTRACT
BACKGROUND: Triggering receptor expressed on myeloid cells 2 (TREM2) is a unique receptor expressed by macrophages in atherosclerotic plaque and is involved in the progression of atherosclerosis. Whether serum soluble TREM2 (sTREM2) levels has a relationship with coronary heart disease (CHD) remains unclear. METHODS: The cross-sectional study included 86 patients with CHD and 86 controls matched with age and sex. Demographic information, medication history, and laboratory data were collected. sTREM2 concentrations were detected by enzyme-linked immunosorbent assay. We compared the sTREM2 levels in two groups and constructed stepwise linear regression analysis for factors related to the sTREM2 level in patients with CHD; we further used the logistic regression model to evaluate the relationship between sTREM2 and CHD. The diagnostic value of sTREM2 and other biomarkers in CHD was evaluated by the receiver operating characteristic curve (ROC). RESULTS: The serum level of sTREM2 in CHD patients is higher than that in controls. In CHD patients, the stepwise linear regression analysis found that sTREM2 levels were correlated with triglyceride (TG), high-density lipoprotein cholesterols (HDL-C), apolipoprotein B (ApoB) and smoking status. Logistic regression models showed that sTREM2 was associated independently with CHD after adjusted confounders. The ROC curve showed a sensitivity of 59.3% and specificity of 81.4% with an area under the curve of 0.781 (95% CI: 0.711-0.852) for the diagnosis of CHD with serum sTREM2 at a cut-off value of > 1104.894 pg/ml, indicating a higher diagnostic value than high sensitivity C reaction protein (hs-CRP) and apolipoprotein B (ApoB). CONCLUSION: In this study, we provide evidence that sTREM2 levels are elevated in CHD patients and are associated with various cardiovascular risk factors. Additionally, sTREM2 demonstrates better diagnostic performance compared to traditional indicators in identifying CHD. These findings suggest that sTREM2 may serve as a potential biomarker for coronary heart disease.
Subject(s)
Atherosclerosis , Coronary Disease , Humans , Cross-Sectional Studies , Coronary Disease/diagnosis , Biomarkers/analysis , C-Reactive Protein/analysis , Apolipoproteins B , Membrane Glycoproteins , Receptors, ImmunologicABSTRACT
Cardiovascular disease (CVD) caused by atherosclerosis is the leading cause of death worldwide. The level of low-density lipoprotein cholesterol (LDL-C), considered as the initiator of atherosclerosis, is the most widely used predictor for CVD risk and LDL-C has been the primary target for lipid-lowering therapies. However, residual CVD risk remains high even with very low levels of LDL-C. This residual CVD risk may be due to remnant cholesterol, high triglyceride levels, and low high-density lipoprotein cholesterol (HDL-C). Non-high density lipoprotein cholesterol (non-HDL-C), which is calculated as total cholesterol minus HDL-C (and represents the cholesterol content of all atherogenic apolipoprotein B-containing lipoproteins), has emerged as a better risk predictor for CVD than LDL-C and an alternative target for CVD risk reduction. Major international guidelines recommend evaluating non-HDL-C as part of atherosclerotic CVD risk assessment, especially in people with high triglycerides, diabetes, obesity, or very low LDL-C. A non-HDL-C target of <130â mg/dL (3.4â mmol/L) has been recommended for patients at very high risk, which is 30â mg/dL (0.8â mmol/L) higher than the corresponding LDL-C target goal. Non-HDL-C lowering approaches include reducing LDL-C and triglyceride levels, increasing HDL-C, or targeting multiple risk factors simultaneously. However, despite the growing evidence for the role of non-HDL-C in residual CVD risk, and recommendations for its assessment in major guidelines, non-HDL-C testing is not routinely done in clinical practice. Thus, there is a need for increased awareness of the need for non-HDL-C testing for ascertaining CVD risk and concomitant prevention of CVD.
Subject(s)
Atherosclerosis , Cardiovascular Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Cholesterol, LDL , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cholesterol , Triglycerides , Risk Factors , Lipoproteins/therapeutic use , Cholesterol, HDL , Atherosclerosis/diagnosis , Atherosclerosis/epidemiology , Atherosclerosis/prevention & controlABSTRACT
AIMS: This study aimed to identify a novel splicing-altering LAMP2 variant associated with Danon disease. METHODS AND RESULTS: To identify the potential genetic mutation in a Chinese pedigree, whole-exome sequencing was conducted in the proband, and Sanger sequencing was performed on the proband's parents. To verify the impact of the splice-site variant, a minigene splicing assay was applied. The AlphaFold2 analysis was used to analyse the mutant protein structure. A splice-site variant (NM_013995.2:c.864+5G>A) located at intron 6 of the LAMP2 gene was identified as a potential pathogenic variant. The minigene splicing revealed that this variant causes exon 6 to be skipped, resulting in a truncated protein. The AlphaFold2 analysis showed that the mutation caused a protein twist direction change, leading to conformational abnormality. CONCLUSIONS: A novel splice-site variant (NM_013995.2:c.864+5G>A) located at intron 6 of the LAMP2 gene was identified. This discovery may enlarge the LAMP2 variant spectrum, promote accurate genetic counselling, and contribute to the diagnosis of Danon disease.
Subject(s)
Glycogen Storage Disease Type IIb , RNA Splicing , Humans , East Asian People , Glycogen Storage Disease Type IIb/genetics , Glycogen Storage Disease Type IIb/diagnosis , Lysosomal-Associated Membrane Protein 2/genetics , Mutation , PedigreeABSTRACT
This review proposes the use of dioleoylphosphatidylglycerol (DOPG) to enhance diabetic wound healing. Initially, the characteristics of diabetic wounds are examined, focusing on the epidermis. Hyperglycemia accompanying diabetes results in enhanced inflammation and oxidative stress in part through the generation of advanced glycation end-products (AGEs), in which glucose is conjugated to macromolecules. These AGEs activate inflammatory pathways; oxidative stress results from increased reactive oxygen species generation by mitochondria rendered dysfunctional by hyperglycemia. These factors work together to reduce the ability of keratinocytes to restore epidermal integrity, contributing to chronic diabetic wounds. DOPG has a pro-proliferative action on keratinocytes (through an unclear mechanism) and exerts an anti-inflammatory effect on keratinocytes and the innate immune system by inhibiting the activation of Toll-like receptors. DOPG has also been found to enhance macrophage mitochondrial function. Since these DOPG effects would be expected to counteract the increased oxidative stress (attributable in part to mitochondrial dysfunction), decreased keratinocyte proliferation, and enhanced inflammation that characterize chronic diabetic wounds, DOPG may be useful in stimulating wound healing. To date, efficacious therapies to promote the healing of chronic diabetic wounds are largely lacking; thus, DOPG may be added to the armamentarium of drugs to enhance diabetic wound healing.
ABSTRACT
Soy protein isolate (SPI) is an attractive natural material for preparing wood adhesives that has found broad application. However, poor mechanical properties and unfavorable water resistance of wood composites with SPI adhesive bonds limit its more extensive utilization. The combination of lysine (Lys) with a small molecular structure as a curing agent for modified soy-based wood adhesive allows Lys to penetrate wood pores easily and can result in better mechanical strength of soy protein-based composites, leading to the formation of strong chemical bonds between the amino acid and wood interface. Scanning electron microscopy (SEM) results showed that the degree of penetration of the S/G/L-9% adhesive into the wood was significantly increased, the voids, such as ducts of wood at the bonding interface, were filled, and the interfacial bonding ability of the plywood was enhanced. Compared with the pure SPI adhesive, the corresponding wood breakage rate was boosted to 84%. The wet shear strength of the modified SPI adhesive was 0.64 MPa. When Lys and glycerol epoxy resin (GER) were added, the wet shear strength of plywood prepared by the S/G/L-9% adhesive reached 1.22 MPa, which increased by 29.8% compared with only GER (0.94 MPa). Furthermore, the resultant SPI adhesive displayed excellent thermostability. Water resistance of S/G/L-9% adhesive was further enhanced with respect to pure SPI and S/GER adhesives through curing with 9% Lys. In addition, this work provides a new and feasible strategy for the development and application of manufacturing low-cost, and renewable biobased adhesives with excellent mechanical properties, a promising alternative to traditional formaldehyde-free adhesives in the wood industry.
Subject(s)
Lysine , Soybean Proteins , Soybean Proteins/chemistry , Lysine/analysis , Epoxy Resins/analysis , Adhesives/chemistry , Wood/chemistry , Water/analysisABSTRACT
Prolonged inflammation and impaired re-epithelization are major contributing factors to chronic non-healing diabetic wounds; diabetes is also characterized by xerosis. Advanced glycation end products (AGEs), and the activation of toll-like receptors (TLRs), can trigger inflammatory responses. Aquaporin-3 (AQP3) plays essential roles in keratinocyte function and skin wound re-epithelialization/re-generation and hydration. Suberanilohydroxamic acid (SAHA), a histone deacetylase inhibitor, mimics the increased acetylation observed in diabetes. We investigated the effects of TLR2/TLR4 activators and AGEs on keratinocyte AQP3 expression in the presence and absence of SAHA. Primary mouse keratinocytes were treated with or without TLR2 agonist Pam3Cys-Ser-(Lys)4 (PAM), TLR4 agonist lipopolysaccharide (LPS), or AGEs, with or without SAHA. We found that (1) PAM and LPS significantly upregulated AQP3 protein basally (without SAHA) and PAM downregulated AQP3 protein with SAHA; and (2) AGEs (100 µg/mL) increased AQP3 protein expression basally and decreased AQP3 levels with SAHA. PAM and AGEs produced similar changes in AQP3 expression, suggesting a common pathway or potential crosstalk between TLR2 and AGEs signaling. Our findings suggest that TLR2 activation and AGEs may be beneficial for wound healing and skin hydration under normal conditions via AQP3 upregulation, but that these pathways are likely deleterious in diabetes chronically through decreased AQP3 expression.
Subject(s)
Aquaporin 3 , Toll-Like Receptor 2 , Mice , Animals , Aquaporin 3/genetics , Aquaporin 3/metabolism , Toll-Like Receptor 2/genetics , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolism , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , Keratinocytes/metabolism , Vorinostat/metabolism , Glycation End Products, Advanced/pharmacology , Glycation End Products, Advanced/metabolismABSTRACT
We introduce an innovative solution approach to the challenging dynamic load-shedding problem which directly affects the stability of large power grid. Our proposed deep Q-network for load-shedding (DQN-LS) determines optimal load-shedding strategy to maintain power system stability by taking into account both spatial and temporal information of a dynamically operating power system, using a convolutional long-short-term memory (ConvLSTM) network to automatically capture dynamic features that are translation-invariant in short-term voltage instability, and by introducing a new design of the reward function. The overall goal for the proposed DQN-LS is to provide real-time, fast, and accurate load-shedding decisions to increase the quality and probability of voltage recovery. To demonstrate the efficacy of our proposed approach and its scalability to large-scale, complex dynamic problems, we utilize the China Southern Grid (CSG) to obtain our test results, which clearly show superior voltage recovery performance by employing the proposed DQN-LS under different and uncertain power system fault conditions. What we have developed and demonstrated in this study, in terms of the scale of the problem, the load-shedding performance obtained, and the DQN-LS approach, have not been demonstrated previously.