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Nitrogen-doped biochar (NBC) is a green material for remediating heavy metal pollution, but it undergoes aging under natural conditions, affecting its interaction with heavy metals. The preparation conditions of NBC were optimized using response surface methodology (RSM), and NBC was subjected to five different aging treatments to analyze the removal efficiency of Cd(II) and soil remediation capability before and after aging. The results indicated that NBC achieved optimal performance with a mass ratio of 5:2.43, an immersion time of 10.66 h, and a pyrolysis temperature of 900 °C. Aging diminished NBC's adsorption capacity for Cd(II) but did not change the main removal mechanism of monolayer chemical adsorption. Freeze-thaw cycles (FT), UV aging (L), and composite aging (U) treatments increased the proportion of bioavailable-Cd, and all aging treatments facilitated the conversion of potentially bioavailable-Cd to non-bioavailable-Cd. The application of NBC and five aged NBCs reduced the proportion of bioavailable-Cd in the soil through precipitation and complexation, increasing the proportion of non-bioavailable-Cd. Aging modifies the physicochemical properties of NBC, thus influencing soil characteristics and ultimately diminishing NBC's ability to passivate Cd in the soil. This study provides reference for the long-term application of biochar in heavy metal-contaminated environments.
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Cádmio , Carvão Vegetal , Nitrogênio , Poluentes do Solo , Cádmio/química , Carvão Vegetal/química , Nitrogênio/química , Poluentes do Solo/química , Adsorção , Poluentes Químicos da Água/química , Recuperação e Remediação Ambiental/métodos , Solo/químicaRESUMO
PURPOSE: This study aimed to investigate the association between the CC-cytokine ligand-2 (CCL2) 2518A/G (rs1024611) single nucleotide polymorphism (SNP) and susceptibility to age-related macular degeneration (AMD). METHODS: PubMed, Embase, Web of Science, and other databases were searched for articles published before August 24, 2023. After searching, data extraction, and quality assessment, meta-analysis and trial sequential analysis were conducted using RevMan 5.4, Stata 17.0, and TSA 0.9.5.10 Beta software. Combined OR, P values, and 95% confidence intervals (CIs) were calculated. Sensitivity analysis, subgroup analysis and publication bias assessment were also performed. RESULTS: Six articles, comprising 1186 cases and 1124 controls, were included. No significant statistical difference was found in six main outcomes. However, due to observed heterogeneity and high sensitivity, subgroup analysis was performed, revealing statistically significant differences across different regions. No significant publication bias was observed. Trial sequential analysis suggested the need for additional follow-up case-control studies to further validate the findings. CONCLUSION: The CCL2 gene 2518A/G (rs1024611) polymorphism is associated with AMD susceptibility. Among Caucasian populations in West Asia and Europe, the G allele is protective against AMD, whereas in East and South Asia, it poses a risk factor.
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Quimiocina CCL2 , Predisposição Genética para Doença , Degeneração Macular , Polimorfismo de Nucleotídeo Único , Humanos , Degeneração Macular/genética , Quimiocina CCL2/genéticaRESUMO
Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer, yet the effectiveness of treatment for HCC patients is significantly hindered by the development of drug resistance to sorafenib. Through the application of ATAC-seq to examine drug-resistant HCC tissues, we identified substantial alterations in chromatin accessibility in sorafenib-resistant patient-derived xenograft (PDX) models. Employing multi-omics data integration analysis, we confirmed TEAD2 as a crucial transcriptional regulator in sorafenib-resistant HCC tissues. Functional assays illustrated that TEAD2 plays a role in promoting HCC progression and enhancing resistance to sorafenib. Mechanistically, we demonstrated that TEAD2 binds to the TAK1 promoter to modulate its expression. Furthermore, we established the involvement of TAK1 in mediating TEAD2-induced sorafenib resistance in HCC, a finding supported by the effectiveness of TAK1 inhibitors. Our research highlights that targeting the TEAD2-TAK1 axis can effectively mitigate drug resistance in HCC patients receiving sorafenib treatment, offering a novel approach for enhancing the treatment outcomes and prognosis of individuals with HCC. Implications: Targeting the TEAD2-TAK1 axis presents a promising therapeutic strategy to overcome sorafenib resistance in HCC, potentially improving treatment outcomes and prognosis for patients.
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Background: This study investigated factors influencing discrepancies between fractional flow reserve (FFR) and resting full-cycle ratio (RFR) in the functional assessment of coronary artery stenosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods: We included 320 diseased vessels from 253 consecutive patients with NSTE-ACS. Vessels were categorized into four groups based on FFR ≤ 0.80 and RFR ≤ 0.89 thresholds: group 1 concordant negative (RFR-/FFR-), group 2 positive RFR and negative FFR (RFR+/FFR-), group 3 negative RFR and positive FFR (RFR-/FFR+), and group 4 concordant positive (RFR+/FFR+). Univariate and multivariate logistic regression analyses were conducted to identify predictors of diagnostic discrepancy between FFR and RFR. Results: Of the 320 diseased vessels, 182 (56.9%) were in group 1 (RFR-/FFR-), 33 (10.3%) in group 2 (RFR+/FFR-), 31 (9.7%) in group 3 (RFR-/FFR+), and 74 (23.1%) in group 4 (RFR+/FFR+). The concordance between FFR and RFR was 80.0%. Notably, left anterior descending artery (LAD) lesions exhibited significantly lower consistency compared to non-LAD lesions (p = 0.001), with distinct differences in FFR and RFR values between these groups (p < 0.001). The presence of a LAD lesion emerged as an independent predictor of diagnostic inconsistency between positive RFR and negative FFR measurements (p = 0.001). Conclusions: LAD involvement independently predicts diagnostic discrepancies between FFR and RFR in evaluating functional coronary artery stenosis in NSTE-ACS patients.
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Superconducting infinite-layer (IL) nickelates offer a new platform for investigating the long-standing problem of high-temperature superconductivity. Many models were proposed to understand the superconducting mechanism of nickelates based on the calculated electronic structure, and the multiple Fermi surfaces and multiple orbitals involved create complications and controversial conclusions. Over the past five years, the lack of direct measurements of the electronic structure has hindered the understanding of nickelate superconductors. Here we fill this gap by directly resolving the electronic structures of the parent compound LaNiO2 and superconducting La0.8Ca0.2NiO2 using angle-resolved photoemission spectroscopy. We find that their Fermi surfaces consist of a quasi-2D hole pocket and a 3D electron pocket at the Brillouin zone corner, whose volumes change upon Ca doping. The Fermi surface topology and band dispersion of the hole pocket closely resemble those observed in hole-doped cuprates. However, the cuprate-like band exhibits significantly higher hole doping in superconducting La0.8Ca0.2NiO2 compared to superconducting cuprates, highlighting the disparities in the electronic states of the superconducting phase. Our observations highlight the novel aspects of the IL nickelates, and pave the way toward the microscopic understanding of the IL nickelate family and its superconductivity.
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Single-unit cell (1 UC) FeSe interfaced with TiOx or FeOx exhibits significantly enhanced superconductivity compared to that of bulk FeSe, with interfacial electron-phonon coupling (EPC) playing a crucial role. However, the reduced dimensionality in 1 UC FeSe, which may drive superconducting fluctuations, complicates our understanding of the enhancement mechanisms. We construct a new superconducting interface, 1 UC FeSe/SrVO3/SrTiO3. Here, the itinerant electrons of highly metallic SrVO3 films can screen all high-energy Fuchs-Kliewer phonons, including those of SrTiO3, making it the first FeSe/oxide system with screened interfacial EPC while maintaining the 1 UC FeSe thickness. Despite comparable doping levels, the heavily electron-doped 1 UC FeSe/SrVO3 exhibits a pairing temperature (Tg â¼ 48 K) lower than those of FeSe/SrTiO3 and FeSe/LaFeO3. Our findings disentangle the contributions of interfacial EPC from dimensionality in terms of enhancing Tg in FeSe/oxide interfaces, underscoring the critical importance of interfacial EPC. This FeSe/VOx interface also provides a platform for studying interfacial superconductivity.
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Background: Patient-ventilator asynchrony (PVA) frequently occurs in mechanically ventilated patients within the ICU and has the potential for harm. Depending solely on the health care team cannot accurately and promptly identify PVA. To address this issue, our team has developed a cloud-based platform for monitoring mechanical ventilation (MV), comprising the PVA-RemoteMonitor system and the 24-h MV analysis report. We conducted a survey to evaluate physicians' satisfaction and acceptance of the platform in 14 ICUs. Methods: Data from medical records, clinical information systems, and ventilators were uploaded to the cloud platform and underwent data processing. The data were analyzed to monitor PVA and displayed in the front-end. The 24-h analysis report for MV was generated for clinical reference. Critical care physicians in 14 hospitals' ICUs that involved in the platform participated in a questionnaire survey, among whom 10 physicians were interviewed to investigate physicians' acceptance and opinions of this system. Results: The PVA-RemoteMonitor system exhibited a high level of specificity in detecting flow insufficiency, premature cycle, delayed cycle, reverse trigger, auto trigger, and overshoot, with sensitivities of 90.31 %, 98.76 %, 99.75 %, 99.97 %, 100 %, and 99.69 %, respectively. The 24-h analysis report supplied essential data about PVA and respiratory mechanics. 86.2 % (75/87) of physicians supported the application of this platform. Conclusions: The PVA-RemoteMonitor system accurately identified PVA, and the MV analysis report provided guidance in controlling PVA. Our platform can effectively assist ICU physicians in the management of ventilated patients.
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Cadmium (Cd) contamination poses a significant threat to agricultural soils and food safety, necessitating effective remediation strategies. Salix species, with their high coverage and Cd accumulating capacity, hold promise for remediation efforts. The rhizosphere microbiome is crucial for enhancing Cd accumulating capacity for Salix. However, the mechanisms by how Salix interacts with its rhizosphere microbiome to enhance Cd extraction remains poorly understood. In this study, we compared the remediation performance of two Salix ecotypes: 51-3 (High Cd-accumulating Ecotype, HAE) and P646 (Low Cd-accumulating Ecotype, LAE). HAE exhibited notable advantages over LAE, with 10.80 % higher plant height, 43.80 % higher biomass, 20.26 % higher Cd accumulation in aboveground tissues (93.09 µg on average), and a superior Cd translocation factor (1.97 on average). Analysis of the rhizosphere bacterial community via 16S rRNA amplicon sequencing revealed that HAE harbored a more diverse bacterial community with a distinct composition compared to LAE. Indicator analysis identified 84 genera specifically enriched in HAE, predominantly belonging to Proteobacteria, Actinobacteria, and Firmicutes, including beneficial microbes such as Streptomyces, Bacillus, and Pseudomonas. Network analysis further elucidated three taxa groups specifically recruited by HAE, which were highly correlated with functional genes that associated with biosynthesis of secondary metabolites, glycan biosynthesis and metabolism, and metabolism of cofactors and vitamins. These functions contribute to enhancing plant growth, Cd uptake, and resistance to Cd in Salix. Overall, our findings highlight the importance of the rhizosphere microbiome in facilitating Cd extraction and provide insights into microbiome-based strategies for sustainable agricultural practices.
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The absorption-dominated graphene porous materials, considered ideal for mitigating electromagnetic pollution, encounter challenges related to intricate structural design. Herein, petal-like graphene porous films with dendritic-like and honeycomb-like pores are prepared by controlling the phase inversion process. The theoretical simulation and experimental results show that PVP K30 modified on the graphene surface via van der Waals interactions promotes graphene to be uniformly enriched on the pore walls. Benefiting from the regulation of graphene distribution and the construction of honeycomb pore structure, when 15 wt % graphene is added, the porous film exhibits absorption-dominated electromagnetic shielding performance, compared with the absence of PVP K30 modification. The total electromagnetic shielding effectiveness is 24.1 dB, an increase of 170%; the electromagnetic reflection coefficient reduces to 2.82 dB; The thermal conductivity reaches 1.1 W/(m K), representing a 104% increase. In addition, the porous film exhibits improved mechanical properties, the tensile strength increases to 6.9 MPa, and the elongation at break increases by 131%. The method adopted in this paper to control the enrichment of graphene in the pore walls during the preparation of honeycomb porous films by the phase inversion method can avoid the agglomeration of graphene and improve the overall performance of the porous graphene porous films.
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Background: The expansion of artificial intelligence (AI) within large language models (LLMs) has the potential to streamline healthcare delivery. Despite the increased use of LLMs, disparities in their performance particularly in different languages, remain underexplored. This study examines the quality of ChatGPT responses in English and Japanese, specifically to questions related to anaesthesiology. Methods: Anaesthesiologists proficient in both languages were recruited as experts in this study. Ten frequently asked questions in anaesthesia were selected and translated for evaluation. Three non-sequential responses from ChatGPT were assessed for content quality (accuracy, comprehensiveness, and safety) and communication quality (understanding, empathy/tone, and ethics) by expert evaluators. Results: Eight anaesthesiologists evaluated English and Japanese LLM responses. The overall quality for all questions combined was higher in English compared with Japanese responses. Content and communication quality were significantly higher in English compared with Japanese LLMs responses (both P<0.001) in all three responses. Comprehensiveness, safety, and understanding were higher scores in English LLM responses. In all three responses, more than half of the evaluators marked overall English responses as better than Japanese responses. Conclusions: English LLM responses to anaesthesia-related frequently asked questions were superior in quality to Japanese responses when assessed by bilingual anaesthesia experts in this report. This study highlights the potential for language-related disparities in healthcare information and the need to improve the quality of AI responses in underrepresented languages. Future studies are needed to explore these disparities in other commonly spoken languages and to compare the performance of different LLMs.
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PURPOSE: To determine whether the overexpression of the Argonaute RNA-induced silencing complex catalytic component 2 (Ago2) improves erectile function in mice after cavernous nerve injury (CNI). MATERIALS AND METHODS: Lentiviruses containing Ago2 open reading frame (ORF) mouse clone (Ago2 O/E) were used to overexpress Ago2, and lentiviruses ORF negative control particles (NC) were used as a negative control. Three days before preparing the CNI model, we injected lentiviruses into the penises of 8-week-old male C57BL/6 mice. Animals were then divided into four groups: the sham operation control group and the CNI+phosphate-buffered saline, CNI+NC, and CNI+Ago2 O/E groups. One week later, erectile function was assessed by electrically stimulating cavernous nerves bilaterally and obtaining intracavernous pressure parameters. Penile tissue was also collected for molecular mechanism studies. RESULTS: Ago2 overexpression improved erectile function in mice after CNI-induced erectile dysfunction (ED). Immunofluorescence staining and Western blot analysis showed that under Ago2 overexpressing conditions, the contents of endothelial cells, pericytes, and neuronal cells increased in the penile tissues of CNI mice, and this was attributed to reduced apoptosis and ROS production. In addition, we also found that Ago2 overexpression could restore penile mitochondrial function, thereby improving erectile function in CNI-induced ED mice. CONCLUSIONS: Our findings demonstrate that Ago2 overexpression can reduce penile cell apoptosis, restore penile mitochondrial function, and improve erectile function in CNI-induced ED mice.
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Apoptose , Proteínas Argonautas , Modelos Animais de Doenças , Disfunção Erétil , Camundongos Endogâmicos C57BL , Mitocôndrias , Ereção Peniana , Pênis , Animais , Masculino , Pênis/inervação , Disfunção Erétil/etiologia , Camundongos , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Mitocôndrias/metabolismo , Ereção Peniana/fisiologia , Traumatismos dos Nervos Periféricos/complicaçõesRESUMO
BACKGROUND: Having a gynecological tumor or undergoing treatment can be a traumatic experience for women, as it affects their self-image and sexual relationships and can lead to psychological reactions. Psychological adjustment following cancer occurrence remains a key issue among the survivors. AIM: To examine the current status of quality of life (QoL), anxiety, and depression in patients with gynecological cancer and to analyze the factors associated with it. METHODS: Data for 160 patients with gynecological malignancies treated at Shanxi Bethune Hospital from June 2020 to June 2023 were collected and analyzed retrospectively. Patients' QoL was assessed using the European Organization for Research on Treatment of Cancer Quality of Life Questionnaire Core 30 and the Functional Assessment of Cancer Therapy-General Questionnaire. Their emotional status was evaluated using the Self-Rating Anxiety/Depression Scale. The associated factors of anxiety and depression were analyzed. RESULTS: The overall QoL score of the patients 6 months after surgery was 76.39 ± 3.63 points. This included low levels of social and emotional function and severe fatigue and pain. The scores for physiological, functional, emotional, social, and family well-being exhibited an upward trend following surgery compared with those before surgery. One month after surgery, some patients experienced anxiety and depression, with an incidence of 18.75% and 18.13%, respectively. Logistic analysis revealed that good sleep was a protective factor against anxiety and depression in patients with gynecological tumors, whereas physical pain was a risk factor. CONCLUSION: Patients with gynecological malignancies often experience anxiety and depression. By analyzing the factors that affect patients' QoL, effective nursing measures can be administered.
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BACKGROUND: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) serves as a pro-angiogenic factor; however, there is to our knowledge currently no reported research on the relationship between HB-EGF and diabetic erectile dysfunction (ED). AIM: In this study we aimed to determine whether HB-EGF can improve the erectile function of streptozotocin-induced diabetic mice and to explore the related mechanisms. METHODS: Eight-week-old male C57BL/6 mice were used for diabetes induction. Diabetes mellitus (DM) was induced by low-dose injections of streptozotocin (50 mg/kg) for 5 consecutive days. Eight weeks after streptozotocin injections, DM was determined by measuring blood glucose and body weight. Diabetic mice were treated with two intracavernous administrations of phosphate-buffered saline (20 µL) or various doses of HB-EGF (days -3 and 0; 1, 5, and 10 µg in 20 µL of phosphate-buffered saline). The angiogenesis effect of HB-EGF was confirmed by tube formation and migration assays in mouse cavernous endothelial cells and mouse cavernous pericytes under high-glucose conditions. Erectile function was measured by electrical stimulation of the cavernous nerve, as well as histological examination and Western blot analysis for mechanism assessment. OUTCOMES: In vitro angiogenesis, cell proliferation, in vivo intracavernous pressure, neurovascular regeneration, cavernous permeability, and survival signaling were the outcomes measured. RESULTS: Expression of HB-EGF was reduced under diabetic conditions. Exogenous HB-EGF induced angiogenesis in mouse cavernous endothelial cells and mouse cavernous pericytes under high-glucose conditions. Erectile function was decreased in the DM group, whereas administration of HB-EGF resulted in a significant improvement of erectile function (91% of the age-matched control group) in association with increased neurovascular content, including cavernous endothelial cells, pericytes, and neuronal cells. Histological and Western blot analyses revealed a significant increase in the permeability of the corpus cavernosum in DM mice, which was attenuated by HB-EGF treatment. The protein expression of phospho-Akt Ser473 and phosphorylated endothelial nitric oxide synthase Ser1177 increased after HB-EGF treatment. CLINICAL IMPLICATIONS: The use of HB-EGF may be an effective strategy to treat ED associated with DM or other neurovascular diseases. STRENGTHS AND LIMITATIONS: Similarly to other pro-angiogenic factors, HB-EGF has dual roles in vascular and neuronal development. Our study focused on broadly evaluating the role of HB-EGF in diabetic ED. In view of the properties of HB-EGF as an angiogenic factor, its dose concentration should be strictly controlled to avoid potential side effects. CONCLUSION: In the diabetic ED mouse model in this study erectile function was improved by HB-EGF, which may provide new treatment strategies for patients with ED who do not respond to phosphodiesterase 5 Inhibitors.
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Hot forming is an effective approach for improving the formability of ultrathin metal sheets, such as those made of stainless steel and pure titanium. However, the increased friction coefficient between the tool and the high-temperature metal sheet negatively affects material flow during hot forming, potentially resulting in severe local thinning or even cracking. This study explores the frictional behavior of 0.1 mm thick ferritic stainless steel (FSS) and commercially pure titanium (CP-Ti) sheets at elevated temperatures. A friction testing apparatus was developed to measure the friction coefficients of these metal sheets from room temperature (25 °C) up to 600 °C. The friction coefficient of the FSS sheet increased monotonically with temperature, whereas that of the CP-Ti sheet first increased and then decreased. Post-friction testing microscopic examination demonstrated that built-up edges formed on the surfaces of the friction blocks when rubbed against the stainless steel, contributing to the higher friction coefficients. This study provides a foundation for understanding frictional behavior during the hot forming of ultrathin metal sheets.
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In biomass pyrolysis for biochar production, existing prediction models face computational challenges and limited accuracy. This study curated a comprehensive dataset, revealing pyrolysis parameters' dominance in biochar yield (54.8 % importance). Pyrolysis temperature emerged as pivotal (PCC = -0.75), influencing yield significantly. Artificial Neural Network (ANN) outperformed Random Forest (RF) in testing set predictions (R2 = 0.95, RMSE = 3.6), making it apt for complex multi-output predictions and software development. The trained ANN model, employed in Partial Dependence Analysis, uncovered nonlinear relationships between biomass characteristics and biochar yield. Findings indicated optimization opportunities, correlating low pyrolysis temperatures, elevated nitrogen content, high fixed carbon, and brief residence times with increased biochar yields. A multi-output ANN model demonstrated optimal fit for biochar yield. A user-friendly Graphical User Interface (GUI) for biochar synthesis prediction was developed, exhibiting robust performance with a mere 0.52 % prediction error for biochar yield. This study showcases practical machine learning application in biochar synthesis, offering valuable insights and predictive tools for optimizing biochar production processes.
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Carvão Vegetal , Redes Neurais de Computação , Carvão Vegetal/química , Pirólise , Biomassa , Aprendizado de MáquinaRESUMO
BACKGROUND: Assessing condyle position postorthognathic surgery is pivotal for optimizing surgical accuracy, sustaining postoperative stability, and ensuring predictable treatment outcomes. PURPOSE: The aim of this study was to analyze the changes of condyle position after orthognathic surgery with different types of jaw deformity and to analyze whether the changes of condyle position are different. STUDY DESIGN, SETTING, SAMPLE: A retrospective cohort study was designed and conducted, involving adults who underwent orthognathic surgery for jaw deformities at the affiliated Stomatological Hospital of Nanchang University between 2019 and 2022. Patients with incomplete computerized tomography data were excluded. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable was time (preoperative and postoperative) and types of jaw deformities (skeletal Class III, skeletal Class II, and mandibular deviation). MAIN OUTCOME VARIABLE(S): The main outcome variables were the three-dimensional linear and rotational positional changes of the condyle. COVARIATES: Evaluated covariates included sex and age. ANALYSES: MIMICS 20.0 software measured all data, and SPSS 22.0 software facilitated statistical analyses. Intragroup and intergroup correlation analyses employed paired t-tests and independent t-tests, with statistical significance set at P < .05. RESULTS: The study sample was composed of 32 subjects with a mean age of 22.43 ± 1.6 and 9 were male. The analysis of changes of condylar position from virtual surgical planning to the immediate postoperative period showed that the maximum condylar displacement was 1.74 mm and the maximum angular change was 3.92°. The analysis of changes in condylar position from the immediate postoperative period to 1 year postoperatively showed no statistically significant changes for the same type of jaw deformity. But patients with Class II malocclusion exhibited distinct condylar displacement and rotation patterns compared to those with Class III malocclusion and mandibular deformity. CONCLUSION AND RELEVANCE: The application of virtual surgical planning in orthognathic surgery ensures a high degree of consistency in achieving the desired condylar position. Moreover, no significant change in condylar position was observed after orthognathic surgery for the same type of jaw deformity. However, patients with Class II deformities exhibited a higher susceptibility to rotational displacement of the condyles compared to those with other types of jaw deformities.
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Erectile dysfunction (ED) affects a significant proportion of men aged 40-70 and is caused by cavernous tissue dysfunction. Presently, the most common treatment for ED is phosphodiesterase 5 inhibitors; however, this is less effective in patients with severe vascular disease such as diabetic ED. Therefore, there is a need for development of new treatment, which requires a better understanding of the cavernous microenvironment and cell-cell communications under diabetic condition. Pericytes are vital in penile erection; however, their dysfunction due to diabetes remains unclear. In this study, we performed single-cell RNA sequencing to understand the cellular landscape of cavernous tissues and cell type-specific transcriptional changes in diabetic ED. We found a decreased expression of genes associated with collagen or extracellular matrix organization and angiogenesis in diabetic fibroblasts, chondrocytes, myofibroblasts, valve-related lymphatic endothelial cells, and pericytes. Moreover, the newly identified pericyte-specific marker, Limb Bud-Heart (Lbh), in mouse and human cavernous tissues, clearly distinguishing pericytes from smooth muscle cells. Cell-cell interaction analysis revealed that pericytes are involved in angiogenesis, adhesion, and migration by communicating with other cell types in the corpus cavernosum; however, these interactions were highly reduced under diabetic conditions. Lbh expression is low in diabetic pericytes, and overexpression of LBH prevents erectile function by regulating neurovascular regeneration. Furthermore, the LBH-interacting proteins (Crystallin Alpha B and Vimentin) were identified in mouse cavernous pericytes through LC-MS/MS analysis, indicating that their interactions were critical for maintaining pericyte function. Thus, our study reveals novel targets and insights into the pathogenesis of ED in patients with diabetes.
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Disfunção Erétil , Pênis , Pericitos , Análise da Expressão Gênica de Célula Única , Animais , Humanos , Masculino , Camundongos , Disfunção Erétil/genética , Disfunção Erétil/metabolismo , Camundongos Endogâmicos C57BL , Pênis/metabolismo , Pericitos/metabolismo , TranscriptomaRESUMO
Several population pharmacokinetic (PPK) models of B cell lymphoma-2 (BCL-2) venetoclax (VEN) have been developed and published to characterize the influencing factors of pharmacokinetics in hematologic malignancies. This review described PPK models of VEN examining the magnitude and types of covariate effects in PK parameters, as well as identified areas that require further investigation in order to facilitate their use. Currently, there are six analyses on PPK models of VEN summarized in this review. Most analyses described the pharmacokinetics of VEN with a two-compartment model and all covariates are categorical. The median estimated apparent clearance (CL/F) was 446 L/Day and apparent volume of distribution of the central compartment (V2/F) was 114.5 L. The median IIV of CL/F reported was 39.5% and V2/F was 46.7%. Most commonly, CYP3A inhibitors, OATP1B3 inhibitors and rituximab co-administration were found to be significant covariates on CL/F. In addition, sex and population were influential covariates on V2/F. A detailed description of the characteristics of PPK models of VEN is provided in this review, as well as the effects of covariates on the PK parameters. For future development of the VEN PPK model, CYP3A inhibitors, rituximab co-administration, OATP1B1 transporter inhibitors, sex, population, and food might be considered. Further research and comprehensive investigations should be undertaken to explore reference ranges for therapeutic drug monitoring, define the potential role of patients with cerebrospinal fluid complications, and assess new or potential covariates. These endeavors will facilitate the development of personalized VEN therapy.
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Antineoplásicos , Compostos Bicíclicos Heterocíclicos com Pontes , Neoplasias Hematológicas , Sulfonamidas , Humanos , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/metabolismo , Sulfonamidas/farmacocinética , Sulfonamidas/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/farmacocinética , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Antineoplásicos/farmacocinética , Modelos BiológicosRESUMO
BACKGROUND: Our team has previously reported physiologic support by the EXTra-uterine Environment for Neonatal Development (EXTEND) of 105 to 117 days gestational age (GA) lambs for up to 28 days with normal organ maturation. However, the fetal lamb brain matures more rapidly, requiring the study of 90-105 day GA fetal lambs to assess more neurodevelopmentally equivalent lambs to the 23-25 week GA extreme premature infant. METHODS: Extremely preterm lambs (90-95 days of GA) were delivered by C-section and supported by EXTEND. Estimated circuit flows were maintained at around 325 ml/kg/min. After support on EXTEND, MRI and histopathologic analysis were performed and compared to 105-112 days GA control lambs. RESULTS: The extremely preterm group includes 10 animals with a mean GA of 91.6 days, a mean weight at cannulation of 0.98 kg and a mean length of stay on EXTEND of 13.5 days (10-21 days). Hemodynamics and oxygenation showed stable parameters. Animals showed growth and physiologic cardiac function. MRI volumetric and diffusion analysis was comparable to controls. Histologic brain analysis revealed no difference between study groups. CONCLUSION: EXTEND appears to support brain and cardiac development in an earlier gestation, less mature, lamb model. IMPACT: Prolonged (up to 21 days) physiological support of extremely preterm lambs of closer neurodevelopmental equivalence to the 24-28 gestational week human was achieved using the EXTEND system. EXTEND treatment supported brain growth and development in extremely preterm fetal lambs and was not associated with intraventricular hemorrhage or white matter injury. Daily echocardiography demonstrated physiologic heart function, absence of cardiac afterload, and normal developmental increase in cardiac chamber dimensions. This study demonstrates hemodynamic and metabolic support by the EXTEND system in the extremely preterm ovine model.
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BACKGROUND: The current understanding of the correlation between TLR4 gene (toll-like receptor 4) rs4986790 and rs4986791 polymorphisms and asthma susceptibility is inconclusive, with studies and populations yielding conflicting results. OBJECTIVES: Evaluate this relationship using meta-analysis and trial sequential analysis (TSA). PATIENTS AND METHODS: Databases were systematically queried for relevant articles from the establishment of the database to 19 June 2023 adhering to predefined inclusion and exclusion criteria. Two authors independently conducted screening, data extraction, and quality evaluation. Meta-analysis and TSA were carried out using RevMan 5.4, StataMP 17.0, and TSA 0.9.5.10 Beta, with α=0.05. Subgroup analyses were conducted based on racial demographics. A sensitivity analysis was conducted employing a one-by-one exclusion method. Publication bias was assessed using the Begg and Egger tests. MAIN OUTCOME MEASURES: Association of asthma susceptibility with TLR4 gene rs4986790 and rs4986791 polymorphisms. SAMPLE SIZE: 23 articles included 22 studies on the rs4986790 polymorphism and 11 studies on the rs4986791 polymorphism on the TLR4 gene. RESULTS: Out of 692 studies screened, 23 met the inclusion criteria. While the overall meta-analysis showed no significant association between the TLR4 rs4986790 polymorphism and asthma susceptibility, subgroup analysis revealed a significant link in the Caucasian population. A significant association was noted in the meta-analysis, particularly among Asian populations, on the rs4986791 polymorphism. The sensitivity analysis indicated that the meta-analysis results were relatively stable. Publication bias analysis revealed minimal influence from publication bias. However, TSA was underscored by the necessity for additional original studies to further validate specific outcomes. CONCLUSIONS: Our study underscores the ethnicity-specific impact on the relationship between TLR4 polymorphisms and asthma susceptibility. While the overall findings for rs4986790 were not significant, the association with the Caucasian population merits further investigation. Furthermore, rs4986791 demonstrated a significant correlation with asthma susceptibility, specifically among Asian populations. LIMITATIONS: Our study predominantly examined the rs4986790 and rs4986791 polymorphisms, overlooking the potential influence of other genetic variants within TLR4.