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PURPOSE: We sought to summarize the value of contrast-enhanced computed tomography (CECT) in the differential diagnosis of bladder paraganglioma (BPG) and bladder cancer. METHODS: The medical records of 19 patients with BPG (13 males, 6 females) and 56 patients with bladder cancer (49 males, 7 females) between November 2007 and June 2023 were retrospectively reviewed. All patients underwent unenhanced and contrast-enhanced CT scanning. RESULTS: Patient age (46.4 ± 11.1 years vs. 58.6 ± 16.0 years), tumor calcification (1/19 vs. 18/56), stalk (0/19 vs. 10/56), internal vessels (15/19 vs. 19/56) and the enlarged adjacent supplying artery (14/19 vs. 10/56) were significantly different between BPG and bladder cancer (P < 0.05). The CT value in the corticomedullary phase (92.4 ± 16.6 HU vs. 64.0 ± 14.5 HU) and the contrast-enhanced value in the corticomedullary phase (54.5 ± 17.4 HU vs. 28.5 ± 12.8 HU) were significantly greater in BPG patients than in bladder cancer patients (P < 0.001), with corresponding area under the curve values of 0.930 and 0.912, respectively. The optimal cutoff values were 83.2 HU and 38.5 HU, respectively. A CT value > 83.2 HU in the corticomedullary phase and a contrast-enhanced CT value > 38.5 HU in the corticomedullary phase were used to indicate BPG with sensitivities of 78.9% and 89.5%, respectively, and specificities of 94.6% and 75.0%, respectively. CONCLUSION: The corticomedullary phase of CECT plays an important role in the preoperative differential diagnosis of BPG and bladder cancer.
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Medios de Contraste , Paraganglioma , Tomografía Computarizada por Rayos X , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Diagnóstico Diferencial , Paraganglioma/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Vejiga Urinaria/diagnóstico por imagenRESUMEN
BACKGROUND: Diabetic nephropathy (DN) is a prevalent chronic microvascular complication of diabetes and the leading cause of end-stage renal disease (ESRD). Understanding the progressive etiology of DN is critical for the development of effective health policies and interventions. Recent research indicated that polystyrene microplastics (PS-MPs) contaminate our diets and accumulate in various organs, including the liver, kidneys, and muscles. METHODS: In this study, ten-week-old db/db mice and db/m mice were fed. Besides, db/db mice were divided into two groups: PS-MPs group (oral administration of 0.5⯵m PS-MPs) and an H2O group, and they were fed for three months. A type II diabetes model was established using db/db mice to investigate the effects of PS-MPs on body weight, blood glucose level, renal function, and renal fibrosis. RESULTS: The results demonstrated that PS-MPs significantly exacerbated various biochemical indicators of renal tissue damage, including fasting blood glucose, serum creatinine, blood urea nitrogen, and blood uric acid. Additionally, PS-MPs worsened the pathological alterations and degree of fibrosis in renal tissue. An increased oxidative stress state and elevated levels of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein-1 (MCP-1) were identified. Furthermore, PS-MPs significantly enhanced renal fibrosis by inhibiting the transition from epithelial cells to mesenchymal cells, specifically through the inhibition of the TGF-ß/Smad signaling pathway. The expression levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, and cleaved Caspase-1, which are inflammasome proteins, were significantly elevated in the PS-MPs group. CONCLUSION: The findings suggested that PS-MPs could aggravate kidney injury and renal fibrosis in db/db mice by promoting NLRP3/Caspase-1 and TGF-ß1/Smads signaling pathways. These findings had implications for elucidating the role of PS-MPs in DN progression, underscoring the necessity for additional research and public health interventions.
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In recent years, microplastics (MPs) have gained significant attention as a persistent environmental pollutant resulting from the decomposition of plastics, leading to their accumulation in the human body. The liver, particularly of individuals with type 2 diabetes mellitus (T2DM), is known to be more susceptible to the adverse effects of environmental pollutants. Therefore, to investigate the potential impact of MPs on the liver of diabetic mice and elucidate the underlying toxicological mechanisms, we exposed db/db mice to 0.5 µm MPs for 3 months. Our results revealed that MPs exposure resulted in several harmful effects, including decreased body weight, disruption of liver structure and function, elevated blood glucose levels, impaired glucose tolerance, and increased glycogen accumulation in the hepatic tissue of the mice. Furthermore, MPs exposure was found to promote hepatic gluconeogenesis by perturbing the PP2A/AMPK/HNF4A signaling pathway. In addition, MPs disrupt redox balance, leading to oxidative damage in the liver. This exposure also disrupted hepatic lipid metabolism, stimulating lipid synthesis while inhibiting catabolism, ultimately resulting in the development of fatty liver. Moreover, MPs were found to induce liver fibrosis by activating the Wnt/ß-catenin signaling pathway. Furthermore, MPs influenced adaptive thermogenesis in brown fat by modulating the expression of uncoupling protein 1 (UCP1) and genes associated with mitochondrial oxidative respiration thermogenesis in brown fat. In conclusion, our study demonstrates that MPs induce oxidative damage in the liver, disturb glucose and lipid metabolism, promote hepatic fibrosis, and influence adaptive thermogenesis in brown fat in diabetic mice. These findings underscore the potential adverse effects of MPs on liver health in individuals with T2DM and highlight the importance of further research in this area.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Ratones , Humanos , Animales , Diabetes Mellitus Tipo 2/metabolismo , Microplásticos , Plásticos/metabolismo , Plásticos/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Vía de Señalización Wnt , Diabetes Mellitus Experimental/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Fibrosis , Hígado , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Factor Nuclear 4 del Hepatocito/metabolismoRESUMEN
The widespread presence of microplastics (MPs) in the environment poses a significant threat to biological survival and human health. However, our understanding of the toxic effects of MPs on the kidneys remains limited. This study aimed to investigate the underlying mechanism of the toxic effects of MPs on the kidneys using an ischemia-reperfusion (IR) mouse model. Four-week-old ICR mice were exposed to 0.5 µm MPs for 12 weeks prior to IR injury. The results showed that MPs exposure could aggravate the IR-induced damage to renal tubules and glomeruli. Although there were no significant changes in blood urea nitrogen and serum creatinine levels 7 days after IR, MPs treatment resulted in a slight increase in both parameters. In addition, the expression levels of inflammatory factors (MCP-1 and IL-6) at the mRNA level, as well as macrophage markers (CD68 and F4/80), were significantly higher in the MPs + IR group than in the Sham group after IR. Furthermore, MPs exposure exacerbated IR-induced renal fibrosis. Importantly, the expression of pyroptosis-related genes, including NLRP3, ASC, GSDMD, cleaved caspase-1, and IL-18, was significantly upregulated by MPs, indicating that MPs exacerbate pyroptosis in the context of renal IR. In conclusion, our findings suggest that MPs exposure can aggravate renal IR-induced pyroptosis by activating NLRP3-GSDMD signaling.
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Proteína con Dominio Pirina 3 de la Familia NLR , Daño por Reperfusión , Humanos , Ratones , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Microplásticos , Plásticos/metabolismo , Ratones Endogámicos ICR , Riñón/metabolismo , Daño por Reperfusión/genéticaRESUMEN
Nanoplastics (NPs) and Microplastics (MPs) pollution has become a severe threat to the planet and is a growing concern. However, their effects on male reproductive toxicity remain poorly understood. In this study, a series of morphological analyses were completed to explore the influence of NPs and MPs exposure on the testis in mice. After 12-weeks exposure, although both NPs and MPs exposure can lead to reproductive toxicity, compared with NPs exposure, exposure to MPs leads to a more significant increase in reproductive toxicity dependent on some particle size. Moreover, increased reproductive toxicities, including increased spermatogenesis disorders, and sperm physiological abnormality, oxidative stress, testis inflammation was more associated with MPs group than NPs group. Ultra-pathological structure observed by transmission electron microscopy indicated that both NPs and MPs have different effects on spermatogonia, spermatocytes and Sertoli cells. Exposure to MPs resulted in decreased Sertoli cell numbers and reduced Leydig cell area, and showed no effects on differentiation of Leydig cells by the expression level of the Insulin-Like factor 3 (INSL3) in Leydig cells. Transcriptomic sequencing analysis provided valuable insights into the differential effects of NPs and MPs on cellular processes. Specifically, our findings demonstrated that NPs were predominantly involved in the regulation of steroid biosynthesis, whereas MPs primarily influenced amino acid metabolism. This study demonstrates the effect of adult-stage reproductive toxicity in mice after exposure to NPs and MPs, which will deep the understanding of the NPs and MPs induced toxicity.
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Microplásticos , Testículo , Masculino , Animales , Ratones , Microplásticos/toxicidad , Plásticos , Semen , EspermatozoidesRESUMEN
Low-grade kaolin is the largest emissions of industrial solid waste that is difficult to dispose of and pollutes the environment seriously. From the perspective of harmless and complete resource utilization, we proposed a novel strategy that combines the wet leaching under mild conditions and physical beneficiation for the facile and low-cost high-valued utilization of low-grade kaolin that involves high-efficiency recovery of aluminum (Al), silicon (Si), and titanium (Ti). The key to successful implementation of this method lies in the new discovery that the residual SiO2 after Al extraction of kaolinite by acid leaching under specific conditions could be rapidly dissolved in dilute NaOH solution at room temperature 25 °C. This highly reactive SiO2 challenges the conventional notions of various silica species are usually chemically stable. By adjusting the key technical parameters of the thermal activation-acid leaching process, the selective and efficient extraction of Al2O3 from low-grade kaolin was realized. The acid leaching residue was then subjected to selective recovery of SiO2 by alkaline leaching at 25 °C to obtain high-quality sodium silicate. Finally, the alkali leaching residue as titanium coarse concentrate was separated by centrifugal concentrator to obtain artificial rutile (TiO2 >91.06%). The key mechanism for the formation of the highly reactive silica was also systematically studied and confirmed.
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Caolín , Residuos Sólidos , Dióxido de Silicio , Titanio , Aluminio , MetalurgiaRESUMEN
Microplastics (MPs) may pollute drinking water, accumulate in the food chain, and release toxic chemicals that may cause a variety of diseases. The detrimental effects of MPs on kidney injury and fibrosis under long-term accumulation have not been fully documented. In this study, mice were exposed to MPs with three different diameters (80 nm, 0.5 µm, and 5 µm) to investigate the detrimental influences of MPs on the kidney. The results showed that MPs of different diameters caused varying degrees of injury to the murine kidney. MPs exposure can induce an inflammatory response, oxidative stress, and cell apoptosis in the kidney and induce kidney injury, which ultimately promotes kidney fibrosis. Furthermore, transcriptome data revealed that chronic exposure to MPs could alter the expressions of multiple genes related to immune response (80 nm) and circadian rhythm (0.5 µm, and 5 µm). Overall, our data provide new evidence and potential research for investigating the harm of MPs to kidney of mammals and even humans.
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Microplásticos , Plásticos , Humanos , Animales , Ratones , RNA-Seq , Riñón , Apoptosis , Poliestirenos , MamíferosRESUMEN
INTRODUCTION: Chronic kidney disease (CKD) is a major public health issue worldwide, which is characterized by irreversible loss of nephron and renal function. However, the molecular mechanism of CKD remains underexplored. METHODS: This study integrated three transcriptional profile datasets to investigate the molecular mechanism of CKD. The differentially expressed genes (DEGs) between Sham control (Con) and unilateral ureteral obstruction (UUO)-operated mice were analyzed by utilizing the limma package in R. The shared DEGs were analyzed by Gene Ontology and functional enrichment. Protein-protein interactions (PPIs) were constructed by utilizing the STRING database. Hub genes were analyzed by MCODE and Cytohubba. We further validated the gene expression by using the other dataset and mouse UUO model. RESULTS: A total of 315 shared DEGs between Con and UUO samples were identified. Gene function and KEGG pathway enrichment revealed that DEGs were mainly enriched in inflammatory response, immune system process, and chemokine signaling pathway. Two modules were clustered based on PPI network analysis. Module 1 contained 13 genes related to macrophage activation, migration, and chemotaxis. Ten hub genes were identified by PPI network analysis. Subsequently, the expression levels of hub genes were validated with the other dataset. Finally, these four validated hub genes were further confirmed by our UUO mice. Three validated hub genes, Gng2, Pf4, and Ccl9, showed significant response to UUO. CONCLUSION: Our study reveals the coordination of genes during UUO and provides a promising gene panel for CKD treatment. GNG2 and PF4 were identified as potential targets for developing CKD drugs.
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Perfilación de la Expresión Génica , Insuficiencia Renal Crónica , Animales , Ratones , Mapas de Interacción de Proteínas/genética , Biomarcadores , Biología Computacional , Insuficiencia Renal Crónica/genéticaRESUMEN
Background: Cancer-associated fibroblasts (CAFs) are the important component of the tumor microenvironment (TME). Previous studies have found that some pro-malignant CAFs participate in the resistance to radiotherapy as well as the initiation and progression of tumor recurrence. However, the exact mechanism of how radiation affects CAFs remains unclear. This study aimed to explore the effect and possible mechanism of radiation-activated CAFs, and its influence on lung cancer. Methods: CAFs were isolated from surgical specimens in situ and irradiated with 8Gy x-rays. The changes in cell morphology and subcellular structure were observed. CAFs marker proteins such as FAP and α-SMA were detected by Western Blotting. Cell counting kit-8 (CCK8) assay, flow cytometry, wound healing assay, and transwell chamber assay was used to detect the activation of cell viability and migration ability. A nude mouse xenograft model was established to observe the tumorigenicity of irradiated CAFs in vivo. The genomic changes of CAFs after radiation activation were analyzed by transcriptome sequencing technology, and the possible mechanisms were analyzed. Results: The CAFs showed a disorderly growth pattern after X-ray irradiation. Subcellular observations suggested that metabolism-related organelles exhibited more activity. The expression level of CAFs-related signature molecules was also increased. The CAFs irradiated by 8Gy had good proliferative activity. In the (indirect) co-culture system, CAFs showed radiation protection and migration induction to lung cancer cell lines, and this influence was more obvious in radiation-activated CAFs. The radiation protection was decreased after exosome inhibitors were applied. Vivo study also showed that radiation-activated CAFs have stronger tumorigenesis. Transcriptome analysis showed that genes were enriched in several pro-cancer signaling pathways in radiation-activated CAFs. Conclusions: Our study confirmed that CAFs could be activated by ionizing radiation. Irradiation-activated CAFs could promote cancer cell proliferation, migration, radiotherapy tolerance, and tumorigenesis. These results suggested that irradiation-activated CAFs might participate in the recurrence of lung cancer after radiotherapy, and the inhibition of CAFs activation may be an important way to improve clinical radiotherapy efficacy.
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Single-metal-atom catalysts (SMACs) have garnered extensive attention for various electrocatalytic applications, owing to their maximum atom-utilization efficiency, tunable electronic structure, and remarkable catalytic performance. In particular, carbon-based SMACs exhibit optimal electrocatalytic activity for the oxygen reduction reaction (ORR) which is of paramount importance for several sustainable energy conversion and generation technologies, such as fuel cells and metal-air batteries. Despite continuous endeavors in developing various advanced carbon-based SMACs for electrocatalytic ORR, the rational regulation of coordination structure and thus the electronic structure of carbon-based SMACs remains challenging. In this review, we critically examine the role of coordination structure, including local coordination structure (i.e., metal atomic centers and the first coordination shell) and extended local coordination structure (i.e., the second and higher coordination shells), on the rational design of carbon-based SMACs for high-efficiency electrocatalytic ORR. Insights into the relevance between coordination structures and their intrinsic ORR activities are emphatically exemplified and discussed. Finally, we also propose the major challenges and future perspectives in the rational design of advanced carbon-based SMACs for electrocatalytic ORR. This review aims to emphasize the significance of coordination structure and deepen the insightful understanding of structure-performance relationships.
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BACKGROUND: The tumor immune microenvironment (TIME) has been recognized to be an imperative factor facilitating the acquisition of many cancer-related hallmarks and is a critical target for targeted biological therapy. This research intended to construct a risk score model premised on TIME-associated genes for prediction of survival and identification of potential drugs for ovarian cancer (OC) patients. METHODS AND RESULTS: The stromal and immune scores were computed utilizing the ESTIMATE algorithm in OC patient samples from The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network and differentially expressed genes analyses were utilized to detect stromal-and immune-related genes. The Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression was utilized for additional gene selection. The genes that were selected were utilized as the input for a stepwise regression to construct a TIME-related risk score (TIMErisk), which was then validated in Gene Expression Omnibus (GEO) database. For the evaluation of the protein expression levels of TIME regulators, the Human Protein Atlas (HPA) dataset was utilized, and for their biological functions, the TIMER and CIBERSORT algorithm, immunoreactivity, and Immune Cell Abundance Identifier (ImmuCellAI) were used. Possible OC medications were forecasted utilizing the Genomics of Drug Sensitivity in Cancer (GDSC) database and connectivity map (CMap). TIMErisk was developed based on ALPK2, CPA3, PTGER3, CTHRC1, PLA2G2D, CXCL11, and ZNF683. High TIMErisk was recognized as a poor factor for survival in the GEO and TCGA databases; subgroup analysis with FIGO stage, grade, lymphatic and venous invasion, debulking, and tumor site also indicated similar results. Functional immune cells corresponded to more incisive immune reactions, including secretion of chemokines and interleukins, natural killer cell cytotoxicity, TNF signaling pathway, and infiltration of activated NK cells, eosinophils, and neutrophils in patients with low TIMErisk. Several small molecular medications which may enhance the prognosis of patients in the TIMErisk subgroup were identified. Lastly, an enhanced predictive performance nomogram was constructed by compounding TIMErisk with the FIGO stage and debulking. CONCLUSION: These findings may offer a valuable indicator for clinical stratification management and personalized therapeutic options for OC patients and may be a foundation for future mechanistic research of their association.
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A climax in the development of cost-effective and high-efficiency transition metal-based electrocatalysts has been witnessed recently for sustainable energy and related conversion technologies. In this regard, structure-activity relationships based on several descriptors have already been proposed to rationally design electrocatalysts. However, the dynamic reconstruction of the surface structures and compositions of catalysts during electrocatalytic water oxidation, especially during the anodic oxygen evolution reaction (OER), complicate the streamlined prediction of the catalytic activity. With the achievements in operando and in situ techniques, it has been found that electrocatalysts undergo surface reconstruction to form the actual active species in situ accompanied with an increase in their oxidation state during OER in alkaline solution. Accordingly, a thorough understanding of the surface reconstruction process plays a critical role in establishing unambiguous structure-composition-property relationships in pursuit of high-efficiency electrocatalysts. However, several issues still need to be explored before high electrocatalytic activities can be realized, as follows: (1) the identification of initiators and pathways for surface reconstruction, (2) establishing the relationships between structure, composition, and electrocatalytic activity, and (3) the rational manipulation of in situ catalyst surface reconstruction. In this review, the recent progress in the surface reconstruction of transition metal-based OER catalysts including oxides, non-oxides, hydroxides and alloys is summarized, emphasizing the fundamental understanding of reconstruction behavior from the original precatalysts to the actual catalysts based on operando analysis and theoretical calculations. The state-of-the-art strategies to tailor the surface reconstruction such as substituting/doping with metals, introducing anions, incorporating oxygen vacancies, tuning morphologies and exploiting plasmonic/thermal/photothermal effects are then introduced. Notably, comprehensive operando/in situ characterization together with computational calculations are responsible for unveiling the improvement mechanism for OER. By delivering the progress, strategies, insights, techniques, and perspectives, this review will provide a comprehensive understanding of the surface reconstruction in transition metal-based OER catalysts and future guidelines for their rational development.
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BACKGROUND: Sacrocolpopexy is the gold standard procedure for treating pelvic organ prolapse (POP) patients with apical defects. Different surgical approaches have emerged and been utilized successively, including traditional laparoscopy, single-hole laparoscopy, robotic laparoscopy, vaginal-assisted laparoscopy, and transvaginal approaches. Robotic sacrocolpopexy (RSC) has attracted increasing attention as an emerging surgical technique and has unique advantages, such as a "simulated wrist" mechanical arm and high-definition three-dimensional (3D) visual field, which has gradually begun to be utilized in the clinical setting. METHODS: We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) reporting checklist, and a systematic literature search was conducted on six databases from their inception to 1st March 2020. We evaluated patients with POP who underwent RSC or laparoscopic sacrocolpopexy (LSC), outcomes (including perioperative outcomes: blood loss, operating times, blood transfusion, and hospital stay), surgery-related complications, as well as cure and recurrence rates. RESULTS: A total of 49 articles were available, including 3,014 patients, among which 18 were comparative studies on LSC vs. RSC, and 31 were non-comparative single-arm studies on RSC. For RSC, median operative time was 226 [90-604] minutes, estimated blood loss was 56 [5-1,500] mL, and hospital stay was 1.55 [1-16] days. Intraoperative complications and postoperative complications occurred in 74 (2.7%) and 360 (13.0%) patients, respectively. Of 2,768 RSC patients, 40 had been converted from a robot-assisted approach to other approaches, and 134 of 1,852 patients (7.2%) have recurrent prolapses of any compartment. Compared to LSC, RSC was associated with significantly lower blood loss and lower conversion rate. However, more operative time was observed in RSC. No significant differences were observed in perioperative transfusion, intraoperative and postoperative complications, or objective recurrence between RSC and LSC. CONCLUSIONS: RSC's application seems to contribute some advantages compared to conventional laparoscopic surgery, although both approaches appear to promote equivalent clinical outcomes. Notably, heterogeneity among studies might have affected the outcome of the study. Consequently, high-quality and large-sample randomized trials comparing both techniques are necessitated.
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The ability to develop highly active and low-cost electrocatalysts represents an important endeavor toward accelerating sluggish water-oxidation kinetics. Herein, we report the implementation and unraveling of the photothermal effect of spinel nanoparticles (NPs) on promoting dynamic active-sites generation to markedly enhance their oxygen evolution reaction (OER) activity via an integrated operando Raman and density functional theory (DFT) study. Specifically, NiFe2O4 (NFO) NPs are first synthesized by capitalizing on amphiphilic star-like diblock copolymers as nanoreactors. Upon the near-infrared light irradiation, the photothermal heating of the NFO-based electrode progressively raises the temperature, accompanied by a marked decrease of overpotential. Accordingly, only an overpotential of 309 mV is required to yield a high current density of 100 mA cm-2, greatly lower than recently reported earth-abundant electrocatalysts. More importantly, the photothermal effect of NFO NPs facilitates surface reconstruction into high-active oxyhydroxides at lower potential (1.36 V) under OER conditions, as revealed by operando Raman spectroelectrochemistry. The DFT calculation corroborates that these reconstructed (Ni,Fe)oxyhydroxides are electrocatalytically active sites as the kinetics barrier is largely reduced over pure NFO without surface reconstruction. Given the diversity of materials (metal oxides, sulfides, phosphides, etc.) possessing the photo-to-thermal conversion, this effect may thus provide a unique and robust platform to boost highly active surface species in nanomaterials for a fundamental understanding of enhanced performance that may underpin future advances in electrocatalysis, photocatalysis, solar-energy conversion, and renewable-energy production.
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AIMS: To explore the clinical characteristics and placental pathological changes of pregnant women with 2019 novel coronavirus (CoV) disease (COVID-19) in the third trimester, and to assess the possibility of vertical transmission. METHODS AND RESULTS: The placenta tissues were evaluated by using immunohistochemistry for inflammatory cells and Hofbauer cells, and using severe acute respiratory syndrome (SARS) CoV-2 RNA Fluorescence In-Situ Hybridization (FISH) and SARS-CoV-2 spike protein immunofluorescence (IF) double staining. All eight placentas from the third trimester pregnancy women were studied. All patients were cured, no clinical or serological evidence pointed to vertical transmission of SARS-CoV-2. Features of maternal vascular malperfusion (MVM) such as increased syncytial knots were present in all 8 cases (8/8), and increased focal perivillous fibrin depositions were presented in 7 cases (7/8). No significate chronic histiocytic intervillositis was noted in the placenta. The number of macrophages and inflammatory cells such as T cells, B cells and plasma cells in the placental villous was not significantly increased in all cases. Moreover, all of eight cases demonstrated negative results by FISH using a SARS-CoV-2 virus RNA probe and by IF using a monoclonal antibody against SARS-CoV-2 spike protein. CONCLUSIONS: We found no evidence of vertical transmission and adverse maternal-fetal outcomes in the placentas of third trimester COVID-19 pregnancy women, which provided further information for the clinical management of those women in the third trimester. However, further studies are still needed for patients with infections in different stage of gestation, especially in first and second trimester.
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COVID-19/virología , Placenta/virología , Complicaciones Infecciosas del Embarazo/virología , SARS-CoV-2/patogenicidad , Adulto , Femenino , Humanos , Embarazo , Tercer Trimestre del Embarazo/inmunología , Mujeres Embarazadas , Glicoproteína de la Espiga del Coronavirus/metabolismoRESUMEN
The effects of SARS-COV-2 infection on the pregnant women and their fetus growth have attracted worldwide concern. Our case study aimed to investigate the neonatal clinical outcomes of the recovered pregnant women from COVID-19 in China, expecting to provide the clinical references of urgent need for other countries. Our study recruited a total of 12 recovered pregnant women from COVID-19 prior to pregnancy termination. The maternal and neonatal clinical characteristics were recorded. Of them, the placental pathological characteristics of five participants were evaluated following the standard guidelines. Two of them chose induced labour due to being worry about the potential adverse effects of medical treatment for COVID-19 by themselves. For the others, 8 gave birth by cesarean section with certain indications and 2 by vaginal delivery. Their neonates were all live birth with ≥ 37 gestational weeks and high Apgar scores of 9 â¼ 10. For the neonate related biological samples, they all have negative results of RNA test, including nasopharyngeal swab, umbilical cord blood, amniotic fluid, vaginal fluid, placenta, or umbilical cord. Most of other pathological indicators of placental examination suggested no abnormal syndromes. Overall, we did not find any abnormal pregnancy complications and neonatal outcomes among them. We concluded that excess adverse effect on the fetus development due to COVID-19 in the recovered pregnant women should be less influential, especially, induce abortion due to the anxiety of COVID-19 treatment should be not advisable.
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COVID-19/complicaciones , Complicaciones Infecciosas del Embarazo , SARS-CoV-2 , Adulto , Femenino , Humanos , Recién Nacido , Placenta/patología , Embarazo , Resultado del Embarazo , Mujeres EmbarazadasRESUMEN
Paeonol (Pae), a phenolic acid compound isolated from the Moutan Cortex, was previously demonstrated to exert multiple anticancer effects. The rational control of autophagy has been considered a potential treatment strategy for epithelial ovarian cancer. However, whether Pae induces autophagy and the relationship between its antitumour activities and autophagy in epithelial ovarian cancer are still unclear. In this study, we found that Pae induced not only antiproliferation activity and apoptosis but also autophagy, and complete autophagic flux was observed in A2780 and SKOV3 cells. In addition, combination treatment with Pae and an autophagy inhibitor (3-methyladenine and hydroxychloroquine) showed significant synergetic effects on inhibiting cell viability and promoting apoptosis in vitro and in the A2780 xenograft model, without severe side effects, which was often had by cisplatin. These results indicate that autophagy induced by Pae has a cytoprotective role in both A2780 and SKOV3 cells. Mechanistically, we found that Pae inhibited the protein kinase B(Akt)/mammalian target of rapamycin (mTOR) pathway. Furthermore, when combined with the inhibitors MK2206 and rapamycin to inhibit Akt and mTOR kinase activity, Pae-induced autophagy was increased. Taken together, our results demonstrate that Pae induced cytoprotective autophagy by inhibiting the Akt/mTOR pathway in ovarian cancer cells. Thus, the strategy of combining Pae with an autophagy inhibitor to block Akt/mTOR-dependent autophagy could enhance the antitumour activity of Pae and warrants further application for the treatment of ovarian cancer.
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Acetofenonas/farmacología , Autofagia/efectos de los fármacos , Citoprotección , Neoplasias Ováricas/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Acetofenonas/química , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citoprotección/efectos de los fármacos , Femenino , Humanos , Hidroxicloroquina/farmacología , Ratones Endogámicos BALB C , Ratones Desnudos , Modelos Biológicos , Neoplasias Ováricas/ultraestructura , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND Ovarian cancer has the highest mortality rate among all female genital tumors because of its insidious onset and drug resistance. Hypoxia-inducible factor 1alpha (HIF-1alpha), one of the best-studied oncogenes, plays an important part in tumor adaptation to microenvironmental hypoxia and was found to be overexpressed in several malignancies, including ovarian cancer. Previous studies found that the effect of HIF-1alpha on cancers may be correlated with autophagy and some signaling pathways, such as PI3K/AKT/mTOR, in several tumors. However, the function and potential mechanism have not been clearly defined. MATERIAL AND METHODS The expression of HIF-1alpha in ovarian cancer tissues were detected by immunohistochemistry. HIF-1alpha was knocked down by siRNA transfection. Cell viability was examined by CCK8 and colony formation assay. Apoptosis and autophagy were detected with flow cytometry, transmission electron microscopy, and laser scanning confocal microscopy, respectively. The proteins related to autophagy and PI3K/AKT/mTOR were detected through Western blot analysis. RESULTS HIF-1alpha was expressed at higher levels in epithelial or metastatic ovarian cancer tissue than in normal fallopian tube tissue. When HIF-1alpha was knocked down by siRNA in A2780 and SKOV3 cells, the viability of ovarian cancer cells was weakened, but the apoptosis and autophagy were strengthened. Accordingly, autophagosome formation increased and the expression of autophagy-related proteins LC3 and P62 increased in HIF-1alpha knockdown cells. The PI3K/Akt/mTOR signaling pathway was also found to be inactivated in HIF-1alpha knockdown cells. CONCLUSIONS These findings show that knockdown of HIF-1alpha promoted autophagy and inhibited the PI3K/AKT/mTOR signaling pathway in ovarian cancer cells.
Asunto(s)
Carcinoma Epitelial de Ovario/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Ováricas/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Apoptosis/fisiología , Autofagia/fisiología , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/patología , Hipoxia de la Célula/fisiología , Línea Celular Tumoral , Proliferación Celular/fisiología , Supervivencia Celular/fisiología , Resistencia a Antineoplásicos , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Fosfatidilinositol 3-Quinasa/genética , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Adult brainstem gliomas belong to a rare and heterogeneous group of brain tumors. The overall prognosis is poor; therapeutic options are limited, given the resistance to radiotherapy and the unclear role of chemotherapy/antiangiogenic therapy. Apatinib, a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor and mildly inhibits c-Kit, PDGFR-ß, RET, and c-SRC, has been reported to show efficacy among some patients with malignant supratentorial gliomas. However, its effect on brainstem glioma has not been reported so far. Herein, a 66-year-old man with brainstem anaplastic astrocytoma isocitrate dehydrogenase (IDH) wild type was treated initially with combined radiotherapy, temozolomide, and apatinib. The patient achieved a complete response by MRI and continues to have an ongoing progression-free survival of over 8 months. To our knowledge, this is the first case report using apatinib to treat brainstem IDH wild-type anaplastic astrocytoma, displaying an excellent outcome. We also summarize cases of adult brainstem glioma treated with antiangiogenic therapy. Experiences using various regimens may improve understanding of this rare disease, and thus help physicians to seek more effective treatments for these patients.
RESUMEN
Eosinophilic fasciitis is a rare scleroderma-like syndrome with an unknown aetiology. The characteristics of this disorder include lymphoplasmacytic inflammation involving the subcutaneous fat septa and fascia. Eosinophilic myositis is diagnosed when inflammation extends into the muscles. Here, we describe four patients who developed eosinophilic fasciitis, three of whom developed eosinophilic fasciitis with myositis. Fascial and muscle biopsies were used to confirm the diagnoses. All the patients presented with musculoskeletal symptoms; their electromyographic examinations showed myogenic lesions [short-duration, low-amplitude and polyphasic motor unit action potentials (MUPs), so-called myopathic changes, frequently with abnormal spontaneous activity], in contrast with findings from other reports.