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The gas diffusion layer (GDL), as the bridge to reactants and electrons in PEMFC, is a carbon-based porous component and would be deformed under compression to induce changes in the distributions of reactants and the corresponding performances of PEMFC; therefore, unmasking the impacts of assembly pressure on the distribution of the reactants in GDL is significant to improve the performance of PEMFC. In the present article, the structural response of GDL to assembly pressure was first studied; the variations in transport properties of GDL and the reactant distributions induced by assembly pressure were then discussed; the impacts on the dynamic performances of PEMFC were finally investigated. From the results, assembly pressure was found to have different effects on the regions of GDL under the rib and channel, significant gaps in GDL porosity and/or GDL permeability existed near the rib/channel transition region to worsen the inhomogeneity of reactants. Suffering assembly pressure, the distribution of current density became uneven, and the current density near the rib-channel border seriously rose to the aggravated risk of MEA thermal damage. Furthermore, the power density at specific efficiencies was raised under certain assembly pressures, which meant suitable assembly pressure(s) existed for better output performances of PEMFC.
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Potentiometric ion-selective electrodes (ISEs), which rely on selective and lipophilic ionophores, are commonly employed in clinical diagnostics. However, there are very limited specific ionophores for the detection of creatinine, a critical biomarker for renal function assessment. In the present research, we designed and synthesized an endo-functionalized cage, which is able to selectively bind the creatininium cation (K a = 8.6 × 105 M-1) through the formation of multiple C-Hâ¯O and N-Hâ¯N hydrogen bonds and cationâ¯π interactions. ISEs prepared with this host show a Nernstian response to creatinine and exhibit excellent selectivity and a low detection limit of 0.95 µM. In addition, the creatinine levels in urine or plasma samples determined by our sensor are consistent with those analyzed using enzymatic assay on a Cobas c702. The method is simple, fast and accurate, and amenable to clinical detection of creatinine levels.
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Frataxin (FXN) is required for iron-sulfur cluster biogenesis, and its loss causes the early-onset neurodegenerative disease Friedreich ataxia (FRDA). Loss of FXN is a susceptibility factor in the development of diabetes, a common metabolic complication after myocardial hypertrophy in patients with FRDA. The underlying mechanism of FXN deficient-induced hyperglycemia in FRDA is, however, poorly understood. In this study, we confirmed that the FXN deficiency mouse model YG8R develops insulin resistance in elder individuals by disturbing lipid metabolic homeostasis in adipose tissues. Evaluation of lipolysis, lipogenesis, and fatty acid ß-oxidation showed that lipolysis is most severely affected in white adipose tissues. Consistently, FXN deficiency significantly decreased expression of lipolytic genes encoding adipose triglyceride lipase (Atgl) and hormone-sensitive lipase (Hsl) resulting in adipocyte enlargement and inflammation. Lipolysis induction by fasting or cold exposure remarkably upregulated FXN expression, though FXN deficiency lessened the competency of lipolysis compared with the control or wild type mice. Moreover, we found that the impairment of lipolysis was present at a young age, a few months earlier than hyperglycemia and insulin resistance. Forskolin, an activator of lipolysis, or pioglitazone, an agonist of PPARγ, improved insulin sensitivity in FXN-deficient adipocytes or mice. We uncovered the interplay between FXN expression and lipolysis and found that impairment of lipolysis, particularly the white adipocytes, is an early event, likely, as a primary cause for insulin resistance in FRDA patients at later age.
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Adipocitos Blancos , Modelos Animales de Enfermedad , Frataxina , Ataxia de Friedreich , Resistencia a la Insulina , Proteínas de Unión a Hierro , Lipólisis , Animales , Ataxia de Friedreich/metabolismo , Ataxia de Friedreich/genética , Ataxia de Friedreich/patología , Ratones , Proteínas de Unión a Hierro/metabolismo , Proteínas de Unión a Hierro/genética , Adipocitos Blancos/metabolismo , Adipocitos Blancos/patología , Masculino , Lipasa/metabolismo , Lipasa/genética , HumanosRESUMEN
Periodontitis, with its persistent nature, causes significant distress for most sufferers. Current treatments, such as mechanical cleaning and surgery, often fail to fully address the underlying overactivation of fibroblasts that drives this degradation. Targeting the post-transcriptional regulation of fibroblasts, particularly at the 3'-untranslated regions (3'UTR) of pathogenic genes, offers a therapeutic strategy for periodontitis. Herein, we developed a DNA nanorobot for this purpose. This system uses a dynamic DNA nanoframework to incorporate therapeutic microRNAs through molecular recognition and covalent bonds, facilitated by DNA monomers modified with disulfide bonds. The assembled-DNA nanoframework is encapsulated in a cell membrane embedded with a fibroblast-targeting peptide. By analyzing the 3'UTR regions of pathogenic fibroblast genes FOSB and JUND, we identified the therapeutic microRNA as miR-1-3p and integrated it into this system. As expected, the DNA nanorobot delivered the internal components to fibroblasts by the targeting peptide and outer membrane that responsively releases miR-1-3p under intracellular glutathione. It resulted in a precise reduction of mRNA and suppression of protein function in pathogenic genes, effectively reprogramming fibroblast behavior. Our results confirm that this approach not only mitigates the inflammation but also promotes tissue regeneration in periodontal models, offering a promising therapeutic avenue for periodontitis.
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Regiones no Traducidas 3' , ADN , Fibroblastos , MicroARNs , Periodontitis , Periodontitis/genética , Periodontitis/patología , Fibroblastos/metabolismo , Regiones no Traducidas 3'/genética , ADN/química , ADN/genética , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Animales , RatonesRESUMEN
Purpose: Although allergic diseases in children are on the rise, there has been no comprehensive investigation of the allergens affecting children with allergic diseases in central China. Therefore, we aimed to analyze the distribution of serum allergen species among children with allergic conditions in central China to inform the prevention, diagnosis, and treatment of childhood allergies. Patients and Methods: A total of 9213 children (5543 males with 2.88 ± 0.04 years old and 3670 females with 2.91 ± 0.05 years old) underwent allergen screening, and serum allergen-specific IgE (sIgE) antibodies were detected using an automated fluorescent enzyme immunoassay system. Results: Our findings revealed a total sIgE-positive rate (sIgE-PR) of 57.83%, with mixed food (42.10%), egg whites (30.83%), milk (28.97%), mixed dust mites (24.57%), and mixed molds (23.20%) being the most prevalent source of allergens. The sIgE-PR for common sources of allergens exhibited significant sex-based differences, with males having greater susceptibility than females (p<0.05). Dust mites were the primary source of inhaled allergens, whereas egg white was the predominant source of food allergens. Sources of food allergens were most dominant among infants (0-3 years old); sIgE-PRs for most source of food allergens decreased with age, whereas those for most source of inhaled allergens increased. The autumn sIgE-PRs for mixed molds, weed pollen combinations, and tree pollen combinations were significantly higher than those found in other seasons (p<0.05). Conclusion: Our findings suggest that sources of allergens profiles in children with allergies vary across age groups and seasons. Understanding these patterns can improve the effective prevention of childhood allergies.
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BACKGROUND: The pathogenesis of psoriasis involves the interaction between keratinocytes and immune cells, leading to immune imbalance. While most current clinical treatment regimens offer rapid symptom relief, they often come with significant side effects. Tetrastigma hemsleyanum polysaccharides (THP), which are naturally nontoxic, possess remarkable immunomodulatory and anti-inflammatory properties. METHODS: In this study, we utilized an imiquimod (IMQ)-induced psoriasis mouse model and a LPS/IL-6-stimulated HaCaT model. The potential and mechanism of action of THP in psoriasis treatment were assessed through methods including Psoriasis Area Severity Index (PASI) scoring, histopathology, flow cytometry, immunoblotting, and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Percutaneous administration of THP significantly alleviated symptoms and manifestations in IMQ-induced psoriatic mice, including improvements in psoriatic skin appearance (erythema, folds, scales), histopathological changes, decreased PASI scores, and spleen index. Additionally, THP suppressed abnormal proliferation of Th17 cells and excessive proliferation and inflammation of keratinocytes. Furthermore, THP exhibited the ability to regulate the JAK/STAT3 signaling pathway. CONCLUSION: Findings from in vivo and in vitro studies suggest that THP can inhibit abnormal cell proliferation and excessive inflammation in lesional skin, balance Th17 immune cells, and disrupt the interaction between keratinocytes and Th17 cells. This mechanism of action may involve the modulation of the JAK/STAT3 signaling pathway, offering potential implications for psoriasis treatment.
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In situ polymerized 1,3-dioxolane (PDOL) is widely utilized to construct solid polymer electrolytes because of its high room-temperature ionic conductivity and good compatibility with lithium metal. However, the current polymerization additives used in PDOL do not effectively contribute to the formation of a robust solid electrolyte interphase (SEI), leading to decreased cycle life. Herein, a film-forming Lewis acid, tris(hexafluoroisopropyl) borate (THB), is demonstrated not only to be a catalyst for the ring-opening polymerization of DOL, but also an additive for the formation of a stable fluorine- and boron-rich SEI to improve the interfacial stability and suppress the Li dendrite growth. Moreover, molecular dynamics simulations and experimental results demonstrate that the introduction of THB can promote the dissociation of lithium salt and release more Li+ while the boron site can effectively restrict the free movement of TFSI- anion, thus increasing Li+ transference numbers (0.76) and ensuring the long-term cycling stability of cells. By using THB-PDOL, a stable cycling of LiâLi symmetric cell for 600 h at a capacity of 0.5 mA h cm-2 can be achieved. Furthermore, employing THB-PDOL in LiâLiFePO4 full cell enables a capacity retention of 98.64% after 300 cycles at 1C and a capacity retention of 95.39% after 200 cycles at a high temperature (60 °C). At the same time, this electrolyte is also suitable for the LiâNCM523 full cell, which also achieves excellent stability of more than 180 cycles. This film-forming Lewis acid additive provides ideas for designing low-cost, high-performance PDOL-based lithium metal batteries.
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Introduction: Noise reduction (NR) algorithms have been integrated into modern digital hearing aids to reduce noise annoyance and enhance speech intelligibility. This study aimed to evaluate the influences of a novel hearing aid NR algorithm on individuals with severe-to-profound hearing loss. Methods: Twenty-five participants with severe-to-profound bilateral sensorineural hearing loss underwent three tests (speech intelligibility, listening effort, and subjective sound quality in noise) to investigate the influences of NR. All three tests were performed under three NR strength levels (Off, Moderate, and Strong) for both speech in noise program (SpiN) and speech in loud noise program (SpiLN), comprising six different hearing aid conditions. Results: NR activation significantly reduced listening effort. Subjective sound quality assessments also exhibited benefits of activated NR in terms of noise suppression, listening comfort, satisfaction, and speech clarity. Discussion: Individuals with severe-to-profound hearing loss still experienced advantages from NR technology in both listening effort measure and subjective sound quality assessments. Importantly, these benefits did not adversely affect speech intelligibility.
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Malnutrition early in life may have adverse effects on health later in life. The relationship between malnutrition and obesity parameters (body mass index [BMI] and waist circumference [WC]) and type 2 diabetes is inconsistent. This study aimed to identify the effects of famine exposure and obesity parameters on type 2 diabetes individually or in combination among middle-aged and older adults in China. Data were extracted from the China Health and Retirement Longitudinal Study Wave1 in 2011. The sample involved 13,065 adults aged 45 to 90. The t- or F test was employed to compare age among groups. The chi-square test was utilized to compare baseline characteristics according to the categorical WC levels/BMI levels/famine exposure and examine between-group differences in type 2 diabetes (diabetes and non-diabetes). Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models to estimate the individual and combined associations of BMI/WC levels and famine exposure with the prevalence of type 2 diabetes. In this study, 1559 (11.93%) individuals were exposed to Chinese famine during their fetal stage, 5132 (39.28%) and 4428 (33.89%) in childhood and adolescence/adulthood, respectively. Among BMI measurements, 3780 (28.93%) were overweight, and 1487 (11.38%) were obese, whereas WC measurements showed that 5408 (41.39%) were obesity. In addition, 831 (45.48%) males and 996 (54.52%) females reported type 2 diabetes. In multivariable-adjusted regression models, obesity parameters and famine exposure were independently associated with type 2 diabetes prevalence among all participants (Pâ <â .001). In the interaction analysis, there existed a trend of higher odds for prevalence of type 2 diabetes across all groups compared to the combination of no-exposed and normal BMI/WC level group (the most increase in odds, adolescence/adulthood-exposed group with central obesity in WC levels: OR 4.51 (95% CI = 3.42-5.95); adolescence/adulthood-exposed group with obesity in BMI levels: OR 5.84 (95% CI = 4.11-8.30; P for interaction <.001). The findings for females exhibited similar to the overall participants, when by gender stratification. Our results suggest famine exposure and obesity parameters have positive combined effects on type 2 diabetes in middle-aged and older adults in China.
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Índice de Masa Corporal , Diabetes Mellitus Tipo 2 , Hambruna , Obesidad , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Anciano , China/epidemiología , Obesidad/epidemiología , Hambruna/estadística & datos numéricos , Circunferencia de la Cintura , Anciano de 80 o más Años , Prevalencia , Estudios LongitudinalesRESUMEN
BACKGROUND: We aimed to investigate the association between OA and treatment with dementia risk and structural brain abnormalities. METHODS: We recruited a total of 466,460 individuals from the UK Biobank to investigate the impact of OA on the incidence of dementia. Among the total population, there were 63,081 participants diagnosed with OA. We subsequently categorised the OA patients into medication and surgery groups based on treatment routes. Cox regression models explored the associations between OA/OA treatment and dementia risk, with the results represented as hazard ratios (HRs) and 95% confidence intervals (95% CI). Linear regression models assessed the associations of OA/OA therapy with alterations in cortical structure. RESULTS: During an average of 11.90 (± 1.01) years of follow-up, 5,627 individuals were diagnosed with all-cause dementia (ACD), including 2,438 AD (Alzheimer's disease), and 1,312 VaD (vascular dementia) cases. Results revealed that OA was associated with the elevated risk of ACD (HR: 1.116; 95% CI: 1.039-1.199) and AD (HR: 1.127; 95% CI: 1.013-1.254). OA therapy lowered the risk of dementia in both medication group (HR: 0.746; 95% CI: 0.652-0.854) and surgery group (HR: 0.841; 95% CI: 0.736-0.960). OA was negatively associated with cortical area, especially precentral, postcentral and temporal regions. CONCLUSIONS: Osteoarthritis increased the likelihood of developing dementia, and had an association with regional brain atrophy. OA treatment lowered the dementia risk. OA is a promising modifiable risk factor for dementia.
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Demencia , Osteoartritis , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Alzheimer/epidemiología , Demencia/epidemiología , Demencia Vascular/epidemiología , Demencia Vascular/diagnóstico , Incidencia , Modelos Lineales , Imagen por Resonancia Magnética , Osteoartritis/epidemiología , Osteoartritis/terapia , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Biobanco del Reino Unido , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are two subtypes of inflammatory bowel disease (IBD) with rapidly increased incidence worldwide. Although multiple factors contribute to the occurrence and progression of IBD, the role of intestinal fungal species (gut mycobiota) in regulating the severity of these conditions has been increasingly recognized. C-type lectin receptors (CLRs) on hematopoietic cells, including Dectin-1, Dectin-2, Dectin-3, Mincle and DC-SIGN, are a group of pattern recognition receptors (PRRs) that primarily recognize fungi and mediate defense responses, such as oxidative stress. Recent studies have demonstrated the indispensable role of CLRs in protecting the colon from intestinal inflammation and mucosal damage. METHODS AND RESULTS: This review provides a comprehensive overview of the role of CLRs in the pathogenesis of IBD. Given the significant impact of mycobiota and oxidative stress in IBD, this review also discusses recent advancements in understanding how these factors exacerbate or ameliorate IBD. Furthermore, the latest developments in CLR-guided IBD therapy are examined to highlight the modulation of CLRs in fungal recognition and oxidative burst during the IBD process. CONCLUSION: This review emphasizes the importance of CLRs in IBD, offering new perspectives on the etiology and therapeutic approaches for this disease.
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INTRODUCTION: The heritability of Alzheimer's disease (AD) is estimated to be 58%-79%. However, known genes can only partially explain the heritability. METHODS: Here, we conducted gene-based exome-wide association study (ExWAS) of rare variants and single-variant ExWAS of common variants, utilizing data of 54,569 clinically diagnosed/proxy AD and related dementia (ADRD) and 295,421 controls from the UK Biobank. RESULTS: Gene-based ExWAS identified 11 genes predicting a higher ADRD risk, including five novel ones, namely FRMD8, DDX1, DNMT3L, MORC1, and TGM2, along with six previously reported ones, SORL1, GRN, PSEN1, ABCA7, GBA, and ADAM10. Single-variant ExWAS identified two ADRD-associated novel genes, SLCO1C1 and NDNF. The identified genes were predominantly enriched in amyloid-ß process pathways, microglia, and brain regions like hippocampus. The druggability evidence suggests that DDX1, DNMT3L, TGM2, SLCO1C1, and NDNF could be effective drug targets. DISCUSSION: Our study contributes to the current body of evidence on the genetic etiology of ADRD. HIGHLIGHTS: Gene-based analyses of rare variants identified five novel genes for Alzheimer's disease and related dementia (ADRD), including FRMD8, DDX1, DNMT3L, MORC1, and TGM2. Single-variant analyses of common variants identified two novel genes for ADRD, including SLCO1C1 and NDNF. The identified genes were predominantly enriched in amyloid-ß process pathways, microglia, and brain regions like hippocampus. DDX1, DNMT3L, TGM2, SLCO1C1, and NDNF could be effective drug targets.
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OBJECTIVE: The Surgical Apgar Score quantifies three intraoperative parameters: lowest heart rate, lowest mean arterial pressure, and estimated blood loss (EBL). This scoring system predicts postoperative complications based on these measured factors. The aim of this study was to investigate the value of modified Surgical Apgar Score (mSAS) in predicting postoperative complications in patients with rectal cancer treated with robotic surgery in order to improve the survival and quality of life of rectal cancer patients. METHODS: The study included patients with rectal cancer who underwent robotic surgery in the Department of Gastrointestinal Surgery at the First Affiliated Hospital of Nanchang University from January 2015 to December 2023. In minimally invasive surgery, we developed a modified Surgical Apgar Score (mSAS) tailored for robotic rectal cancer surgery, incorporating an adjusted threshold for EBL. This threshold was derived from quartile analysis of a cohort of 524 patients, with a median EBL of 100 mL (IQR 80-130 mL). We analyzed the association of postoperative complications with low mSAS. RESULTS: This study included 524 patients, of which 91 (17.4%) experienced complications and 22 (4.2%) suffered severe complications. mSAS of 6 provided maximal Youden index and were determined as the cut-off values. The area under the ROC curve for predicting complications using the mSAS was 0.740. Univariate and multivariate analyses indicated that an older age, lower tumor localization, longer operation time, radiotherapy alone, combined chemoradiotherapy, and lower mSAS as independent risk factors for complications. The AUC of the prediction nomogram was 0.834 (95% CI 0.774-0.867). The calibration curve demonstrated excellent concordance with the nomogram, indicating the prediction curve ft the diagonal well. CONCLUSION: This study suggests that mSAS might be a valuable predictive indicator for postoperative complications following robotic rectal cancer surgery, with potentially higher clinical utility.
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Gut bacteria might play an important role in male reproductive disorders, such as male infertility and sperm abnormalities; however, their causal role is unclear. Herein, Mendelian randomization (MR)-Egger, weighted median, inverse variance weighting, Simple mode, and Weighted mode were used to test the causal relationship between gut microbes and male reproductive diseases. The MR results were validated using various metrics. The MR results were also consolidated using reverse causality speculation, conducted using two-way MR analysis and Steiger filtering. Biological function was analysed using enrichment analyses. The results suggested that eight intestinal microflorae were causally associated with male infertility. The Eubacterium oxidoreducens group was associated with an increased risk of male infertility, while the family Bacteroidaceae was negatively associated with male reproductive diseases. Eight intestinal microflorae were causally associated with abnormal spermatozoa. The family Streptococcaceae was associated with a high risk of abnormal spermatozoa, whereas the family Porphyromonadaceae was associated with a low risk of abnormal spermatozoa. No pleiotropy was observed, this study identified a high correlation between the gut flora and the likelihood of male reproductive diseases. Future research will attempt to advance microbial-focused treatments for such diseases.
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Microbioma Gastrointestinal , Infertilidad Masculina , Análisis de la Aleatorización Mendeliana , Masculino , Humanos , Microbioma Gastrointestinal/genética , Infertilidad Masculina/microbiología , Infertilidad Masculina/genética , Espermatozoides/microbiologíaRESUMEN
Long non-coding RNA (LncRNA) plays an important role in malignant transformation of cells. This study aimed to explore the role of Lnc-ENST00000535078 in the malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) induced by coal tar pitch extract (CTPE). The malignant transformation model of BEAS-2B cells exposed to CTPE. Cell proliferation was examined by Cell counting kit-8 (CCK-8) assay. Colony formation assay was used to assess the colony of cells. Cell migration and invasion were detected by Transwell analysis. Cell cycle progression and apoptotic status were assessed by flow cytometry. Differentially expressed genes were screened by RNA sequencing. The results showed that Lnc-ENST00000535078 expression was highest in malignantly transformed BEAS-2B cells passaged to the 30th generation. Knockdown of Lnc-ENST00000535078 inhibited the migration, invasion and anti-apoptotic abilities of malignantly transformed BEAS-2B cells. Transcriptome analysis found 608 differential genes. CCND1 and FOS genes were screened out because of their levels were positive correlation with the expression of Lnc-ENST00000535078, which were consistent with the RNA sequencing results. In conclusion, Low expression of Lnc-ENST00000535078 inhibits the migration and invasion of malignant transformed BEAS-2B cells and promotes apoptosis in these cells. Lnc-ENST00000556926 might affect the malignant transformation of cells through the regulation of CCND1 and FOS. This study may provide a potential target for intervention in CTPE-induced lung cancer.
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The exploration potential within deep-water petroliferous basins holds great promise for oil and gas resources. However, the dearth of geochemical and isotopic data poses a formidable challenge in comprehending the intricate hydrocarbon charging processes, thereby impeding the comprehensive understanding of hydrocarbon accumulation mechanisms and models. Consequently, the establishment of robust source-reservoir relationships in deep-water petroliferous basins represents a pivotal challenge that significantly influences the exploration strategies and the comprehension of hydrocarbon enrichment dynamics within such basins. In this study, we introduce a novel approach, termed the "source-reservoir dynamic evaluation method," tailored to investigate reservoir accumulation models in deep-water petroliferous basins. This method uses basin simulation technology to recover the thermal evolution history and hydrocarbon generation and expulsion history of source rocks, and on this basis delimits the hydrocarbon kitchen range. At the same time, the maturity of source rocks corresponding to crude oil and natural gas in typical reservoirs is calculated. Then, when the thermal evolution degree of source rocks adjacent to the reservoir reaches this maturity, the corresponding geological period is the main charging period of hydrocarbon. As a typical deep-water petroliferous basin, the Santos Basin in Brazil has abundant oil and gas reservoirs under the thick salt rock, but there are still some fundamental problems such as unclear oil-gas accumulation process and model. Therefore, in this paper, the main charging periods of typical hydrocarbon reservoirs are determined based on the internal relationship between the thermal evolution history of the main source rocks and the maturity of crude oil and natural gas, and then the hydrocarbon accumulation process is analyzed and the dynamic accumulation model is established. Finally, the favorable prospecting direction is pointed out. The results show that the oil and gas in the Barra Velha Formation in the Santos basin are mainly derived from the Itapema Formation lacustrine shale source rock, and the source rock is mainly developed in the Eastern Sag of the Central Depression, and its main hydrocarbon generation period is from the deposition period of Florianopolis Formation to the deposition period of Santos Formation. The main hydrocarbon expulsion period was from the deposition period of the Santos Formation to the Early deposition of the Iguape Formation. The oil and gas in the Barra Velha Formation were mainly charged from the Late deposition period of the Santos Formation to the Early deposition period of the Iguape Formation. During this period, the hydrocarbon migrated vertically along the normal fault formed in the rift period to the trap of the adjacent inheritance structural highs and accumulated in the reservoir, which was dominated by the accumulation model of the "lower generation-upper reservoir-salt cap". Since the Barra Velha Formation has the characteristics of near-source accumulation, based on the hydrocarbon expulsion center and hydrocarbon expulsion intensity of the source rock of the Itapema Formation, the distribution ranges of 85% and 50% Pre-salt accumulation probability in the Santos basin were calculated by using the quantitative analysis model of the hydrocarbon distribution threshold. It is suggested that the next oil and gas exploration should be carried out in the paleo-structural highs and slope of Class I favorable area (the hydrocarbon accumulation probability is more than 85%) and Class II favorable area (the hydrocarbon accumulation probability is 85-50%).
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BACKGROUND: Information transmission between primary tumor cells and immunocytes or stromal cells in distal organs is a critical factor in the formation of pre-metastatic niche (PMN). Understanding this mechanism is essential for developing effective therapeutic strategy against tumor metastasis. Our study aims to prove the hypothesis that circ-0034880-enriched tumor-derived extracellular vesicles (TEVs) mediate the formation of PMN and colorectal cancer liver metastasis (CRLM), and targeting circ-0034880-enriched TEVs might be an effective therapeutic strategy against PMN formation and CRLM. METHODS: We utilized qPCR and FISH to measure circRNAs expression levels in human CRC plasma, primary CRC tissues, and liver metastatic tissues. Additionally, we employed immunofluorescence, RNA sequencing, and in vivo experiments to assess the effect mechanism of circ-0034880-enriched TEVs on PMN formation and CRC metastasis. DARTS, CETSA and computational docking modeling were applied to explore the pharmacological effects of Ginsenoside Rb1 in impeding PMN formation. RESULTS: We found that circ-0034880 was highly enriched in plasma extracellular vesicles (EVs) derived from CRC patients and closely associated with CRLM. Functionally, circ-0034880-enriched TEVs entered the liver tissues and were absorbed by macrophages in the liver through bloodstream. Mechanically, TEVs-released circ-0034880 enhanced the activation of SPP1highCD206+ pro-tumor macrophages, reshaping the metastasis-supportive host stromal microenvironment and promoting overt metastasis. Importantly, our mechanistic findings led us to discover that the natural product Ginsenoside Rb1 impeded the activation of SPP1highCD206+ pro-tumor macrophages by reducing circ-0034880 biogenesis, thereby suppressing PMN formation and inhibiting CRLM. CONCLUSIONS: Circ-0034880-enriched TEVs facilitate strong interaction between primary tumor cells and SPP1highCD206+ pro-tumor macrophages, promoting PMN formation and CRLM. These findings suggest the potential of using Ginsenoside Rb1 as an alternative therapeutic agent to reshape PMN formation and prevent CRLM.
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Neoplasias Colorrectales , Vesículas Extracelulares , Neoplasias Hepáticas , Osteopontina , ARN Circular , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Vesículas Extracelulares/metabolismo , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Ratones , Animales , ARN Circular/genética , Osteopontina/metabolismo , Osteopontina/genética , Línea Celular Tumoral , Microambiente Tumoral , Masculino , Femenino , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/inmunología , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
Objective: This study aimed to investigate the value of artificial intelligence (AI) for distinguishing pathological subtypes of invasive pulmonary adenocarcinomas in patients with subsolid nodules (SSNs). Materials and methods: This retrospective study included 110 consecutive patients with 120 SSNs. The qualitative and quantitative imaging characteristics of SSNs were extracted automatically using an artificially intelligent assessment system. Then, radiologists had to verify these characteristics again. We split all cases into two groups: non-IA including 11 Atypical adenomatous hyperplasia (AAH) and 25 adenocarcinoma in situ (AIS) or IA including 7 minimally invasive adenocarcinoma (MIA) and 77 invasive adenocarcinoma (IAC). Variables that exhibited statistically significant differences between the non-IA and IA in the univariate analysis were included in the multivariate logistic regression analysis. Receiver operating characteristic (ROC) analyses were conducted to determine the cut-off values and their diagnostic performances. Results: Multivariate logistic regression analysis showed that the major diameter (odds ratio [OR] = 1.38; 95 % confidence interval [CI], 1.02-1.87; P = 0.036) and entropy of three-dimensional(3D) CT value (OR = 3.73, 95 % CI, 1.13-2.33, P = 0.031) were independent risk factors for adenocarcinomas. The cut-off values of the major diameter and the entropy of 3D CT value for the diagnosis of invasive adenocarcinoma were 15.5 mm and 5.17, respectively. To improve the classification performance, we fused the major diameter and the entropy of 3D CT value as a combined model, and the (AUCï¼ of the model was 0.868 (sensitivity = 0.845, specificity = 0.806). Conclusion: The major diameter and entropy of 3D CT value can distinguish non-IA from IA. AI can improve performance in distinguishing pathological subtypes of invasive pulmonary adenocarcinomas in patients with SSNs.
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This study reports on the modification of bacterial cellulose (BC) membranes produced by static fermentation of Komagataeibacter xylinus bacterial strains with graphene oxide-silver nanoparticles (GO-Ag) to yield skin wound dressings with improved antibacterial properties. The GO-Ag sheets were synthesized through chemical reduction with sodium citrate and were utilized to functionalize the BC membranes (BC/GO-Ag). The BC/GO-Ag composites were characterized to determine their surface charge, morphology, exudate absorption, antimicrobial activity, and cytotoxicity by using fibroblast cells. The antimicrobial activity of the wound dressings was assessed against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The results indicate that the BC/GO-Ag dressings can inhibit â¼70% of E. coli cells. Our findings also revealed that the porous BC/GO-Ag antimicrobial dressings can efficiently retain 94% of exudate absorption after exposure to simulated body fluid (SBF) for 24 h. These results suggest that the dressings could absorb excess exudate from the wound during clinical application, maintaining adequate moisture, and promoting the proliferation of epithelial cells. The BC/GO-Ag hybrid materials exhibited excellent mechanical flexibility and low cytotoxicity to fibroblast cells, making excellent wound dressings able to control bacterial infectious processes and promote the fast healing of dermal lesions.
Asunto(s)
Antibacterianos , Materiales Biocompatibles , Celulosa , Escherichia coli , Grafito , Ensayo de Materiales , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Plata , Staphylococcus aureus , Cicatrización de Heridas , Grafito/química , Grafito/farmacología , Plata/química , Plata/farmacología , Cicatrización de Heridas/efectos de los fármacos , Celulosa/química , Celulosa/farmacología , Nanopartículas del Metal/química , Antibacterianos/química , Antibacterianos/farmacología , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Tamaño de la Partícula , Pseudomonas aeruginosa/efectos de los fármacos , Gluconacetobacter xylinus/química , Humanos , Ratones , Vendajes , AnimalesRESUMEN
INTRODUCTION: Symtomatic hemorrhagic transformation(sHT) was defined as any intracerebral hemorrhage that combined with clinical deterioration. While recent studies showed low rates of sHT in large core ischemic strokes treated with endovascular thrombectomy (EVT), the specific impact of core size on overall hemorrhagic transformation (HT) remains unclear. We aim to investigate the relationship between ischemic core size and development of HT post thrombectomy. METHODS: This prospective study enrolled acute ischemic stroke (AIS) patients with anterior large vessel occlusion undergoing EVT who had baseline MRI from 2017 to 2019. Pre-EVT Arterial Spin Labeling (ASL) and Diffusion-Weighted Imaging (DWI) scans were performed for volume calculations. Primary outcome was HT assessed within 72 h post EVT. Multivariable logistic regression was used to analyze the associations between baseline DWI and ASL volumes and HT occurrence. Discriminative ability for HT was compared using receiver operating curve analysis (c-statistic). RESULTS: We included 101 patients (median age: 64 [IQR 56-74] years, baseline NIHSS 13 [IQR 9-16]). Median DWI and ASL volume were 21.0 ml [IQR 8.3-47.2] and 105 ml [59.5-172.9], respectively. 16.8 % recieved intravenous thrombolysis before EVT. HT occurred in 36.6 % of patients, including 16.8 % with sHT. Baseline DWI volume was independently associated with HT (OR = 1.030, 95 % CI 1.008 to 1.053, P = 0.009), while ASL volume wasn't statistically significant(P = 0.330). The DWI model was superior to ASL model in predicting HT within 72 h (c-statistic, 0.787).Neither DWI (P = 0.149) nor ASL volume (P = 0.834) effectively indicated sHT. CONCLUSIONS: DWI-based ischemic core volume correlates significantly with HT within 72 h post successful thrombectomy. This highlights the potential clinical utility of DWI in guiding treatment decisions for this population.